Acidente Vascular Encefálico (AVE) é uma neuropatologia caracterizada como o
surgimento súbito global ou focal de déficits da função neurológica de duração
superior a 24 horas ou que leve a morte, cuja única causa reside na origem vascular.
Estudos sobre a incidência, comprometimento físico e mortalidade enquadram o AVE
como a segunda causa de morte no mundo e a principal complicação orgânica que
leva às disfunções físico-neurológicas, frequentemente, graves e permanentes. A
indução do AVE em animais de experimentação e o entendimento de sua
fisiopatologia, bem como a busca de tratamentos que minimizem os danos
neurológicos e estimulem a recuperação morfofuncional do indivíduo afetado são
temas de grande relevância científica e clínica. Neste estudo, investigamos os
possíveis efeitos neuroprotetores e/ou anti-inflamatórios do extrato supercrítico de
gergelim preto (Sesamun indicum L.) após lesão isquêmica focal por microinjeções de
80 pmol de endotelina-1 no estriado de ratos adultos, usando as coordenadas
estereotáxicas: 1,2 mm, anterior-posterior; 2,5 mm, médio-lateral; 4,0 mm,
dorsoventral. Após a indução do AVE, os grupos controles foram tratados com tween
a 5% e os tratados receberam 150 mg/kg de gergelim, ambos, por via intraperitoneal,
em duas doses diárias de 75 mg/kg. A neuropatologia foi obtida em secções
encefálicas com 50 e 20 μm de espessuras e coradas com violeta de cresila, para
identificar a área de lesão, e/ou imunomarcadas por anticorpos específicos à
identificação de neurônios (anti-NeuN), astrócitos (anti-GFAP) e micróglia (anti-ED1).
Secções de 5 μm de espessura de rim e fígado corados por métodos histológicos e
histoquímicos não mostraram alterações morfológicas nas células que compõem
esses órgãos essenciais, sugerindo baixa toxicidade do extrato. Todas as secções
coradas e/ou imunomarcadas foram visualizadas em microscópio óptico e seus
campos mais ilustrativos, em todos os tempos de sobrevida e grupos experimentais,
foram capturados digitalmente e editados em computador. A quantificação das células
NeuN+(neurônios), micróglia/macrófagos (ED1+) e astrócitos (GFAP+) na área de
lesão, três secções por lâmina, todo campo ao redor de lesão por secção, com auxílio
de uma gradícula de área 0,0625 mm2 na ocular possibilitou o teste t-Student à análise
estatística entre os grupos e o uso do programa Microsoft Excel à plotagem dos
gráficos. Por fim, uma caracterização da citotoxicidade in vitro, bem como a verificação
do índice de acidez do extrato revelou baixa acidez e mínima agressividade em células
sanguíneas, que ratifica o uso do extrato supercrítico em estudos que visem o
tratamento de doenças agudas e crônicas no SNC.

A disfunção hepatocelular associada ao quadro de malária tem
como principais alterações a insuficiência hepática, hepatoesplenomegalia e
aumento das enzimas hepáticas. Diversos estudam já elucidaram que tais
alterações hepáticas podem ser ocasionadas pelo aumento dos níveis amônia,
que consequentemente pode levar à disfunção no sistema nervoso central
(SNC), ocasionando um quadro de encefalopatia hepática, culminando em
aumento da resposta inflamatória, edema cerebral, desregulação de
neurotransmissores e alterações cognitivas e locomotoras. Objetivo.
Caracterizar as possíveis alterações no sistema nervoso central a partir de uma
lesão hepática induzida pela infecção por Plasmodium berghei ANKA em
modelo murino de malária não complicada. Metodologia. Para isso foram

utilizados camundongos da linhagem Balb-c (20-25g) entre 45-54 dias pós-
natal (CEUA no 2229290317), inoculados com ~106 de eritrócitos parasitados

via intraperitoneal. O delineamento experimental foi divido em duas partes:
Primeiramente foram caracterizadas a curva de sobrevivência, parasitemia,
massa corpórea, sinais clínicos, alterações hepáticas e histológicas,
neuroquímica, presença de edema cerebral, extravasamento vascular, resposta
inflamatória, alterações comportamentais e quantificação dos níveis de amônia
nos grupos controle e PbA. Posteriormente, foi realizado um tratamento com
lactulose para verificar se as alterações encontradas nos experimentos
anteriores eram em decorrência do aumento dos níveis de amônia no cérebro
dos animais. Para isso os grupos foram divididos em: grupo controle, lactulose
3mg/kg, PbA e PbA+lactulose 3mg/kg, no qual foi avaliado a curva de
sobrevivência, parasitemia e atividade locomotora pelo protocolo SHIRPA. Os
resultados foram expressos como média+desvio padrão. Foi realizado o
ANOVA (uma via), pós teste Tukey, considerando como significativo p<0,05.
Resultados. Nossos dados demonstraram que o grupo PbA apresentou
alterações nas funções hepáticas como aumento dos níveis de AST e ALP, BT
e BD, alterações morfológicas como a hepatoesplenomegalia, além das
alterações histológicas evidenciar infiltrado inflamatório, deposição do pigmento
malárico e hiperplasia das células de Kupffer, demonstrando dessa forma um
quadro de falência hepática. Após caracterizar a lesão hepática, buscamos
entender se essas alterações poderiam gerar um comprometimento no SNC, o
qual observamos um comprometimento cognitivo e motor, além de alterações
nos níveis dos neurotransmissores GABA e glutamato, acompanhado com
aumento da resposta inflamatória, edema cerebral e disfunção na barreira
hematoencefálica. Uma vez demonstrado a falência hepática e,
consequentemente, a presença de alterações cognitiva e comportamentais,
buscou-se avaliar os níveis de amônia no cérebro dos animais controle e PbA
na fase inicial da infecção. Nesse sentido, a quantificação dos níveis de
amônia, evidenciou um aumento no 10o d.p.i., no tecido cerebral quando
comparado com o grupo controle, em que os níveis estavam dentro do
esperado em relação a atividade locomotora, ao aplicarmos o protocolo no
grupo infectado e tratado com lactulose, foi possivel observar que o grupo PbA
apresentou alterações no comportamento motor, quando comparado com o
grupo controle. Em contrapartida, o grupo PbA+Lactulose 3mg/kg apresentou
uma atenuação das alterações cognitivas e comportamentais, evidenciando
que a terapia com lacutolose consegue atenuar o quadro cognitivo quanto ao 10 comportamento motor, força e tônus muscular, reflexo e função sensorial. Conclusão. Concluimos que a falência hepática ocasiona um quadro de encefalopatia hepática em modelo murino de malária não complicada, o qual culmina para alterações no sistema nervoso central, pelo aumento dos níveis de amônia no cérebro, e ao realizar o sequestro da amônia com o auxilio do tratamento com lactulose na dose de 3mg/kg, esta consegue atenuar os danos neurológicos dos animais com malária não complicada, demonstrando que as alterações comportamentais são provenientes de um quadro de encefalopatia hepática, ocasionada pelo aumento dos níveis de amônia no córtex dos animais infectados.

O açaí (Euterpe oleracea MART) é uma fruta de grande importância para a região
Amazônica em termos nutricionais, culturais e socioeconômicos. Nos últimos anos, o açaí
tem sido alvo de diversos estudos devido às suas propriedades benéficas à saúde,
incluindo efeitos contra células tumorais. Portanto, o presente trabalho teve como
objetivo avaliar in vitro os efeitos genotóxicos e citotóxicos do extrato clarificado de suco
de açaí em uma linhagem celular de câncer gástrico humano metastático (células AGP01).
Para fins de comparação, utilizou-se uma linhagem celular não transformada de células
epiteliais renais de macaco verde africano (células VERO). Foram realizados o ensaio de
viabilidade por redução de resazurina, o ensaio cometa, a determinação da morte celular
por corantes fluorescentes diferenciais e o ensaio de migração para cicatrização de feridas.
Foi observada redução na viabilidade apenas na linhagem AGP01 em 72h. Não houve
dano genotóxico ou morte celular (através de apoptose ou necrose) em nenhuma das
linhagens celulares. Entretanto, o extrato de açaí induziu redução da motilidade em ambas
as linhagens celulares. A redução da viabilidade celular e a indução do efeito
antimigratório na linhagem celular AGP01 abrem perspectivas para explorar o potencial
da Euterpe oleracea como adjuvante no tratamento do câncer gástrico.

O

O acidente vascular encefálico (AVE) é resultante da oclusão (isquemia - AVEi) ou da
ruptura (hemorragia - AVEh) de vasos sanguíneos no sistema nervoso central (SNC), ocasiona
eventos bioquímicos complexos que causam danos ao metabolismo energético das células
nervosas, disfunção da barreira hematoencefálica e, eventualmente, morte celular de neurônios
e células da glia. Diversos estudos experimentais estão buscando estratégias de promover
melhora nas repercussões funcionais e sociais em indivíduos que sofreram AVE. A prática de
exercícios físicos vem sendo discutida e reconhecida na literatura científica como um fator
importante estratégia de reabilitação para as repercussões clínicas neurológicas e envolve a
redução do estresse oxidativo, a liberação de fatores de crescimento celular no SNC e o aumento
das chances de recuperação funcional. Dessa forma, o presente projeto avaliou os efeitos da
atividade física voluntária na recuperação funcional e na área de lesão em modelo experimental
de AVE isquêmico (AVEi) focal na representação sensório-motora (S1/M1) da pata anterior.
Utilizamos modelos de experimentação animal (Rattus novergicus, todos machos e da linhagem
Wistar) que sofreram indução experimental de AVEi através do uso de microinjeções do
vasoconstritor Endotelina-1 (ET-1). Os animais foram organizados nos grupos experimentais:
grupo controle (GC), grupo sham (GS), AVE sem atividade física voluntária (AVE) e AVE

com atividade física voluntária (AVE+EX). Foram realizados os testes para avaliação sensório-
motora staircase e da escada horizontal durante a fase aguda do AVEi (baseline e 3, 7 e 14 dias

após AVEi). Os procedimentos histológicos de coloração de Nissl foram usados para análise da
área de lesão. Por fim, os dados foram analisados com o auxílio do sofware GraphPad Prism8
por meio da análise de variância (ANOVA) de uma via corrigidas por pós-teste Tukey ou teste
Kruskal-Wallis. A significância estatística foi de p<0,05 e todos os dados foram apresentados
como média ± desvio padrão. Neste estudo a atividade de corrida voluntária promoveu a
recuperação funcional, com repercussões na melhora do desempenho motor no teste da escada
horizontal (F (2,223, 15,56) = [20,29], p<0,0001), além da manutenção da taxa de sucesso no
teste staircase (F (3, 48) = 3,629, p=0,0193). Assim, apesar de não possuir influência sob o
tamanho da área de lesão, a atividade física voluntaria foi capaz de promover a melhora dos
déficits sensório motores, gerando recuperação funcional.

O Finger Tapping Test (FTT) é um teste neuropsicológico clássico que avalia o funcionamento
motor e recentemente tem sido utilizado por meio de smartphones. Nos protocolos clássicos,
observou-se que o sexo e a dominância manual influenciam o desempenho durante o teste. Ao
avaliar a influência do sexo e da dominância manual no teste, é possível ajustar as medições de
desempenho para garantir a validade dos resultados do teste e evitar viés relacionado ao sexo e
à dominância manual. O presente estudo teve como objetivo avaliar a influência do sexo e da
dominância manual no desempenho de participantes em protocolos de FTT baseado em
smartphones. Foi desenvolvido um aplicativo Android para a realização do FTT e recrutou-se
40 homens e 40 mulheres para realizar três protocolos com diferentes desenhos espaciais
(protocolos I, II e III). O desempenho dos participantes foi medido usando os parâmetros
globais, temporais e espaciais do FTT. Foi observado que, para o desempenho no protocolo I,
a dominância manual teve uma influência significativa nas variáveis globais e temporais,
enquanto a interação entre dominância manual e sexo teve uma influência maior nas variáveis
espaciais. Para os protocolos II e III, observamos que a dominância manual teve uma influência
significativa nas variáveis globais, temporais e espaciais em comparação com outros fatores.
Conclui-se que o teste baseado em smartphone é parcialmente influenciado pela dominância
manual e pelo sexo e esses fatores devem ser considerados durante a avaliação do FTT baseado
em smartphone.

A Doença de Parkinson (DP) é uma desordem neurodegenerativa progressiva que
afeta regiões encefálicas cuja circuitaria neural é responsável pelo controle dos movimentos
voluntários. Além dos sintomas motores, pacientes com DP apresentam sintomas não-motores
que afetam drasticamente sua qualidade de vida. Estes incluem alterações cognitivas dentre as
quais destacam-se déficits na memória de trabalho, déficits de funções executivas e na
habilidade de dedução dos estados mentais de outrem (Teoria da Mente: TM) e podem ter
relação também com as funções dos neurônios espelho (NE). Os NE são neurônios ativados
quando uma pessoa realiza ou observa uma dada ação, realizando assim simulação “interna”
dos atos observados, um processo necessário para a capacidade de reconhecimento de
emoções e intenções na TM. Sua atividade é influenciada pelo treino prévio das ações
motoras observadas e pode ser registrada usando-se eletroencefalografia (EEG) através de
alterações nas amplitudes de onda da banda Mu (ondas alfa 1) detectadas quando um
indivíduo observa as ações de outra pessoa. O presente trabalho investigou os efeitos de
terapia motora sobre a atividade eletroencefalográfica e suas correlações com funções da TM
em pacientes acometidos pela DP. Para tal, foram realizadas avaliações eletroencefalográficas
para investigação de padrões de dessincronização característicos da atividade de neurônios
espelho, além dos testes Reading the Mind in the Eyes (RME) e Faux Pas Recognition (FPR).
Avaliamos pacientes diagnosticados com a DP (n=09), sob esquema farmacológico, Hoehn e
Yahr 2-4, de ambos os sexos e com idades com média de 62.9 ± 7.1 anos e média de 5,8 ± 1,3
anos de diagnóstico, em janelas temporais antes do ingresso no projeto (Teste) e após doze
meses de participação realizando 2 sessões semanais (Reteste) de terapia motora baseada em
movimento de dança. Os dados tabulados foram analisados usando o teste t de Student. Não
foram observadas diferenças significativas nos parâmetros de avaliação do teste FPR nas
janelas temporais de Teste e Reteste. Já no teste RMT, a pontuação média obtida pelos
participantes no Teste foi de 9,7 pontos, enquanto no Reteste a média foi de 11,3 pontos, com
significância observada de p=0,0148. A análise estatística eletroencefalográfica (TRPs)
apresentou resultados significativos no nível de dessincronização das ondas alfa 1 (p=0,014
ep=0,010). Os resultados demonstram que embora os indivíduos não apresentem melhora no
desempenho na maioria dos componentes dos testes TM analisados, os resultados de EEG
indicam alteração de atividade cortical cerebral específica relacionada à ativação do sistema
de neurônios-espelho, influenciada pela terapia motora baseada em movimentos de dança o
que a torna uma opção terapêutica adjuvante no tratamento dos sintomas motores e não
motores de pessoas acometidas por DP.

Interindividual variability in cognitive performances has been investigated as they may provide important clues about the multivariate age-related cognitive decline. In the present work, we searched for cognitive variability, similarities, and differences between elderly and young people. For this, we used hierarchical cluster and canonical discriminant function analysis of cognitive scores using specific and sensitive tasks from the Cambridge Neuropsychology Test Automated Battery - CANTAB. Among 415 tested volunteers, three distinct cognitive groups were found, mainly based on working memory and episodic memory scores: group 1 was composed almost exclusively of young adults, while groups 2 and 3 were composed predominantly of elderly adults. Although group 1was the youngest group with the highest level of education compared to the other groups, 18% of young people shared similar performances with elderly group 2 while 5% shared cognitive similarities with group 3. As compared to group 1, elderly groups 2 and 3 had equally lower scores in working memory, but as compared to group 3, group 2 showed greater performances in reaction time, sustained attention, and episodic memory. When the hierarchical cluster and discriminant function analyzes were limited to the same age group, we found 4 and 5 distinct clusters among young adults and elderly people respectively. Episodic memory, sustained attention, and reaction time most contributed to group formation in the elderly, while working memory and sustained attention contributed to cluster formation of young adults. Cognitive variability across subjects showed significant dispersion in rapid visual processing, spatial working memory, reaction time, and paired associated learning. The comparative analysis of these differences showed that they do not occur in the same direction and magnitude between individuals, cognitive domains, and tasks. We found that elderly with greater education (larger cognitive reserve) and active lifestyle deviated less from young adult reference group. Taken together, our data highlight the importance of studying variability as an instrument for the early detection of subtle cognitive declines and to interpret results that deviate from normality.

Os genes p16 e PTEN fazem parte da família dos genes supressores de tumor comumente associados à inativação de uma variedade de cânceres humanos. A perda de sua expressãotem sido estudada mundialmente no Carcinoma Epidermóide Bucal (CEB). Neste estudo, avaliou-se a hipótese de que p16 coopera com PTEN inativo durante a patogênese do CEB, especialmente na agressividade e proliferação do tumor. Para tanto, utilizou-se 119 amostras de CEB nas quais foram avaliadas a relação entre a infecção por HPV, a expressão de
p16 e mutações em PTEN através das técnicas de imunohistoquímica (IHC), western blot e  imunofluorescência. Os resultados deste estudo demonstraram que PTEN possui alta positividade em pacientes com tumor de tamanho mais avançado (p <0,01) e metástase linfonodal (p = 0,02). A análise estatística evidenciou que a expressão de p16 foi fortemente associada à presença de HPV (p <0,0001), mas que sua expressão aberrantenão está relacionada com PTEN alterado (p=0.52). Observou-se também que 60% das amostras em estágio IV (estágio avançado do tumor) estavam estatisticamente associadas a presença de mutação. Conclui-se que PTEN e p16 são genes supressores que controlam a progressão tumoral. No estudo atual, PTEN demonstrou maior reatividade em estágios avançados da doença (superior a sete vezes). O p16 foi fortemente associado ao HPV, mas não demonstrou associação significativa com nenhum fator clínico- patológico analisado. Ambas as proteínas apresentam grande importância no prognóstico dos pacientes. Foi demonstrado que a presença viral diminui a agressividade do tumor. Lesões em estágios avançados apresentam menor sobrevida, além disso, a presença de mutação foi mais comumente observada em estágios avançados da doença. Observou-se que pacientes fumantes com ausência de p16 estão significativamente associados a uma taxa de sobrevida duas vezes menor.

Os tremores são distúrbios comuns caracterizados por uma oscilação
involuntária e relativamente rítmica que pode ocorrer em qualquer parte do corpo,
podendo ser fisiológico ou associado a alguma condição patológica. Sabe-se que o
carregamento de massa pode alterar a distribuição espectral de potência do tremor.
Atualmente, muitos instrumentos têm sido utilizados na avaliação de tremores com
sensores inerciais embutidos, que podem diferir significativamente na massa do
dispositivo. Objetivo: O objetivo deste estudo foi comparar a quantificação do tremor
da mão usando análise espectral de Fourier obtidas a partir de leituras de acelerômetros
embutidos em um dispositivo portátil leve (wearable) e um aparelho de telefonia móvel
comercial (smartphone). Métodos: Foram recrutados 28 indivíduos destros saudáveis
com idades variando de 18 a 40 anos. Em cada participante foi registrado o tremor da
mão em repouso e sob adoção de postura ativa usando wearable (6 g) e smartphone
(170 g) e foi feita análise de Fourier para estudar o espectro de frequências do tremor e
foram comparadas características espectrais nas faixas entre 0 e 5 Hz e 5 e 12 Hz entre
os registros obtidos pelos dois aparelhos. Resultados: Os principais achados desta tese
mostram que na condição de repouso o espectro de tremor da mão teve maior amplitude
de pico na faixa entre 5 e 12 Hz quando o tremor foi registrado com smartphones, e na
condição postural houve pico de energia e frequência de pico significativamente
maiores nos tremores registrados com smartphones na mão dominante. Conclusões:
Dispositivos com massas diferentes podem alterar as características do espectro do
tremor da mão e suas comparações mútuas podem ser prejudicadas.

Tem duas formas de pensar como e feito o processo de tomada de decisões. O processo pode ser
automático ou pode ser modulado por processos linguísticos – de uma forma deliberada-. Além, as
lutas geram um ambiente de alta emocionalidade, apresentando-se a ansiedade. O objetivo deste
estudo e entender como o processo de tomada de decisões, a ansiedade e a impulsividade apresentada
na atividade física do combate, uma luta de judô, donde tem decisões constante em respostas
constantes em tempo limitado. Para fazer isto, dois grupos de participantes (30 lutadores e 15 não
lutadores), os lutadores se dividiram em dois subgrupos (15 lutadores em um grupo e 15 lutadores em
outro). Um dos grupos assistiu um vídeo antecipando os movimentos dos lutadores com um
questionário e o outro grupo fui filmado em uma luta. Os dois grupos também fizeram um teste de
impulsividade e outro de ansiedade. Cada participante tinha mais de 4,5 anos de treinamento e era
competidor. Foram encontradas diferenças nas decisões que os participantes executavam na luta com
as que eles falavam, especificamente quando faziam uma ação. Também fui encontrada diferencia
significativa entre os lutadores e constróis apresentando os lutadores maiores níveis de ansiedade não
fue encontrada diferencia significativa em quanto a impulsividade entre os grupos. Os resultados desta
pesquisa ajudam a entender como e a cognição em judocas, indicando focos para futuros programas de
treinamento e preparação para competição dos atletas

Written language arose about 5000 years ago, which is a relatively short period in evolutionary terms for the appearance of a specific neural system for decoding orthographic characters. Literacy thus depends on the recycling of brain circuits originally evolved for the routine processing of sensory, motor and language functions. The aim of this study is to investigate the association between reading competence and the ability for holistic visual processing in a group of schoolchildren. We recruited 140 (one hundred and forty) volunteers (girls: 6-10 ± 8.5 y.o.; boys: 6-10 ± 8.2 y.o.) enrolled in the first to fifth year of elementary School. Participants we submitted to a reading evaluation and the Mooney's face test, which assesses perceptual closure. Our results demonstrate that the performance of boys aged 6-10 years is different from that of girls in the same age group for the reading competence test and in the perceptual closure test, with the boys showing superior performance. These findings demonstrate that the development of reading competence and holistic visual skills are not dissociated in childhood and have important implications for children's literacy.

O desenvolvimento ocular é um processo complexo orquestrado por vários eventos que
incluem: especificação, morfogênese e diferenciação celular. Todos esses processos de
desenvolvimento e funcionamento do olho são extremamente conservados entre as espécies de
vertebrados viventes, entretanto, por vezes são observadas adaptações interessantes, como em
peixes do gênero Anableps. Ao contrário da maioria dos peixes, que usam os olhos para a
exploração de um mundo submerso, em Anableps anableps (Anablepidae:
Cyprinodontiformes), o olho é adaptado para a percepção simultânea de um mundo acima e
abaixo d’água. Essas adaptações excepcionais incluem: córneas e pupilas duplicadas, bem
como retina especializada contendo regiões associadas à visão aérea e aquática simultânea, e
que expressam genes de modo assimétrico. Recentemente, por análise transcriptômica dos
olhos em desenvolvimento de A. anableps, 20 genes de opsinas não visuais foram identificados
sendo assimetricamente expressos entre estágios pré e pós duplicação de córneas e pupilas.
Desse modo, aqui, analisamos por hibridização in situ a expressão de uma opsina biestável
(Parapinopsin) e uma neuropsina (Opn5) em larvas de A. anableps. Nossos dados mostraram
que o padrão de expressão gênico destas opsinas é simétrico entre a retina dorsal e ventral,
respectivamente, havendo expressão nas camadas CNE, CNI e CCG. Investigamos também a
expressão de três genes de melanopsinas não visuais (opn4x1, opn4x2, opn4m3), uma opsina
de tecido múltiplo teleósteo (tmt1b), e duas opsinas visuais (lws e rh2-1) nas retinas dorsal e
ventral de A. anableps, logo após alterarmos as condições fóticas em que os peixes juvenis se
encontravam. Mostramos que na transição de um ambiente de alta turbidez para um de água
límpida, as opsinas alteram seus padrões de expressão gênica. Adicionalmente, por
imunofluorescência, desvendamos a expressão de Lamin A/C e γ-cristalino, proteínas que
fazem parte do desenvolvimento ocular em A. anableps e que são expressas de forma similar a
de outros organismos em desenvolvimento. Portanto, acreditamos que as informações aqui
descritas elucidam muitos aspectos dos mecanismos moleculares por trás do desenvolvimento
e da plasticidade adaptativa dos olhos de A. anableps.

Embora muitos avanços tenham sido alcançados nos estudos sobre células gliais no Sistema Nervoso Central (SNC), em regiões periféricas como o sistema auditivo periférico, pouco se sabe sobre o papel das células gliais que envolvem os neurônios ganglionares ao longo de toda a via auditiva. A cóclea é um órgão sensorial do sistema auditivo periférico responsável pela recepção e propagação de estímulos periféricos até o sistema nervoso central. O principal neurotransmissor que medeia as sinapses excitatórias na cóclea é o L-
Glutamato, cuja ação excessiva sob seus receptores tem sido associada a danos na função auditiva. Nesse sentido, ressalta-se o papel crucial de mecanismos de transporte de glutamato capazes de regular a concentração extracelular desse neurotransmissor nos espaços sináptico e extra sináptico para a manutenção da função normal da cóclea. Dentro desse contexto, neste estudo buscamos investigar a atividade e expressão de sistemas de transporte de glutamato em modelo in vitro de culturas primárias de células gliais cocleares obtidas de camundongos (Balb/C) neonatos. Para isso, determinamos o transporte de glutamato dependente e independente de sódio por meio de ensaios de captação e liberação utilizando diferentes estratégias
farmacológicas. A quantificação de glutamato extracelular em cada amostra foi realizada por meio de Cromatografia Líquida de Alta Eficiência acoplada a um detector de fluorescência. Por fim, as células foram submetidas ao ensaio de imunofluorescência para marcação do transportador de glutamato independente de sódio X CG . Em nossos resultados, demonstramos que as células gliais medeiam a captação de glutamato por meio de um mecanismo independente de sódio que apresenta uma atividade proeminente quando comparado a astrócitos do córtex. Além disso, identificamos pela primeira vez a expressão do transportador X CG - em células gliais da cóclea, principal representante da família de transportadores de glutamato independente de sódio. Tais dados sugerem um possível papel deste transportador no controle das concentrações extracelulares de glutamato e regulação do estado redox, que pode auxiliar na preservação da função auditiva.

These project aims to establish a model to asses’ emotions in zebrafish (Danio rerio) that can be used in other species and contexts. This idea came up because there is not a reliable model for the assessment of long-term emotional valence, especially the positive one. Most of the time what is measured is the arousal or physical activity and frequently short-term negative emotions. This happens with most of the animal welfare assessments and preclinical models that evaluate emotions.
Although currently is impossible to directly evaluate the subjective aspect of emotion in animals, this research will try to set up a more objective and robust evaluation of animals´ emotional valence by measuring the observable components (behaviour and physiology) of emotion along with the cognitive process which allow to indirectly infer the subjective component of emotion from the bi-directional interaction between emotions and cognition.
Also, we are going to study personality to assess the effects of individuality on long-term emotions, this will allow to differentiate those effects related to emotional traits from those related to emotional states induced by mood manipulation. Moreover, personality assessment will allow us to evaluate emotional mood-trait interactions.
Furthermore, we are aimed to give more validity to the model by measuring other parameters and correlate them all together. As the multifactorial nature of emotions cannot be measured completely by having into account one or few parameters. Thus, besides the cognitive bias and personality assessment, we are going to measure behaviours according to natural history, we will assess anxiety (Dark/light) and frightening (Salinity) responses to add more validity and evaluate stress coping and finally we are going to evaluate neuronal activity to correlate emotional states and brain areas.
This way we are planning to have a better approach to the animal´s point of view regarding the best housing conditions that allow them to deal better with stress and to have a better mood and consequently a good quality of life.

Introduction: Sudden loss of smell is among the first and most prevalent symptoms of COVID-19, where the main symptoms of SARS-CoV-2 infection are flu-like, such as fever, cough and asthenia. The symptoms of COVID-19 vary between individuals, from asymptomatic infection to severe respiratory failure, in addition to a variety of other symptoms. Which can affect, among others, olfactory and gustatory dysfunctions. The sense of smell ranges from detecting warning odors in the environment to building our most pleasurable experiences. This is a process that involves a complex neural network, including the temporal lobe, the amygdala, the insula and a large part of the limbic lobe: the loss of smell should not only be considered as a sensory symptom, but also as a complex syndrome. psycho-sensory. Objective: With that, this work aims to evaluate the olfactory selectivity and trigeminal sensation in the olfactory alterations reported by patients diagnosed with COVID-19. Materials and Methods: Randomized case-control study involving 88 COVID-19-related patients with persistent anosmia or hyposmia after SARS-CoV-2 infection. Forty-four patients diagnosed with COVID-19 underwent evaluation by the Mini Mental Examination test, data collection form, olfactory identification test, olfactory memory test, olfactory threshold test and trigeminal sensation test. Results: In the identification test for the 4 odorants in their essences, it showed a selectivity of the patients to identify certain odors, however, the vast majority of them were not able to identify the odorant of the banana essence. For the short-term olfactory memory test, the results were visible and significant for the errors being more presented in the CoVID-19 group when compared to the control, in the olfactory threshold, differences in perception were observed between the groups. Absence of at least one trigeminal chemosensory function during the test period was reported by 24 patients (58%). The identification of lavender-induced cooling sensation was correct in 20 patients (52%).

The Echimyidae family is considered the most taxonomically diverse among South American
rodents, comprising 25 genera and 93 species. The subfamily Eumysopinae is represented by
nine genera, among which we highlight the arboreal genera Mesomys, which has four
recognized species, and Lonchothrix described as monotypic (L. emiliae), both distributed in
the Amazon. Morphological, molecular and chromosomal studies in the genera Mesomys and
Lonchothrix have helped to improve taxonomic delineation, phylogenetic relationships and
karyotypic patterns. Phylogenetic investigations have helped to elucidate hidden diversity,
suggesting that these taxa are more diverse than previously assumed. Furthermore, the
distribution limits in the Amazon for M. hispidus and M. stimulax have been questioned by
some authors. In this sense, the objective of this study is to understand the karyotypic
evolution of the genera and the geographic limits of the mentioned species. Samples of
Mesomys and Lonchothrix from different locations in the Brazilian Amazon were analyzed
using classical and molecular cytogenetics (telomeric probes and 18S rDNA), and by
sequences of the mitochondrial gene Cytochrome b (Cytb) and Cytochrome C Oxidase -
Subunit I (COI). Our results indicate a new species not yet described for the genus Mesomys
(Mesomys sp. n.) presenting the same karyotypic formula as M. stimulax (2n=60/NF=110),
while M. hispidus presented 2n=60/NF=112, unprecedented for the genre. L. emiliae
presented 2n=66/NF=126, unprecedented for the genus. Constitutive heterochromatin (HC)
was distributed in the centromeric region of all chromosomes of M. hispidus, M. stimulax and
L. emiliae, including the sex chromosomes, with the exception of Mesomys sp. no. who
presented HC distributed in the proximal region of all chromosomes, including the sexual
ones; FISH with telomeric probes showed distal markings in both genders, in addition,
interstitial marking was observed in two chromosome pairs in L. emiliae; FISH with 18S
rDNA probe showed interstitial staining in only one pair in both genders. Phylogenetic
analysis confirmed Mesomys and Lonchothrix as sister genera, showed a high rate of
intraspecific variation in M. hispidus and Mesomys sp. no. may be related to a new lineage in
the genus.

Aggression is a set of complex actions that involve several factors of a genetic, neurophysiological, hormonal and behavioral nature. Furthermore, the brain redox state can also influence aggressive behavior in different species. Thus, modulators of this process can influence the expression of aggressive episodes, between them is the Endocannabinoid System that acts as the main neuromodulator of the CNS, in addition to exerting an antioxidant effect in different conditions. However, its participation in the modulation of aggressive-like behavior needs to be better understood. In this context, this study evaluated the role of cannabinoid receptor type 1 (CB1r) in brain redox state and aggressive-like behavior in Danio rerio (Zebrafish). For this, 68 animals were subdivided into groups: (a) Control (n=26), (b) ACEA (n=30) and (c) AM-251 (n=12), all treated with the drugs of interest: (a) Vehicle (NaCl 0.9%); (b) ACEA agonist 1 mg/kg; (c) 1 mg/kg AM-251 antagonist. The animals were isolated in pairs, without physical contact for 24 hours, followed by pre-treatment and after 30 minutes of pharmacokinetics, the fights were filmed for 30 minutes, the individuals were identified as Dominant or Subordinate and the brains were collected for evaluation of the state brain redox of these individuals. Our results demonstrate, for the first time, that the activation of CB1r by the ACEA agonist modulates aggressive-like behavior and, consequently, partially interferes with the establishment of social hierarchy in Zebrafish, through a redox-independent mechanism. We suggest, therefore, that acute treatment targeting CB1r is a useful neuropharmacological tool to elucidate the role of CES in social interaction and aggressive behavior, allowing a translation with numerous pathologies that have aggression as a behavioral disorder.

Glioma is a rare type of tumour, which acts on Nervous System in a very aggressive way, presents problems in its diagnosis, low effective treatments and survival time less than one year after diagnosis. Due to factors such as intratumoral cell variability, inefficient chemotherapy drugs, adaptive resistance development to the drugs and tumour recurrence after resection, the development of new drugs becomes necessary. In this sense, molecules analogues to endocannabinoids such as fatty amides are a good alternative, since scientific literature shows that they can act as antitumor agents through the interaction with the endocannabinoid system, which modulates many metabolic pathways related to cancer. In this work, two fatty amides synthetized from andiroba (Carapa guianensis aublet) using lipase from Candida antarctica-B (CAL-B) oil were tested aiming to evaluated its potential in the glioma treatment in vitro (C6). AGs reduced C6 cell  viability in a dose dependent manner while were not toxic to normal glia cells. Both FAA1 and FAA2 caused apoptosis cell death and also loss of mitochondrial integrity probably by inhibiting PI3k/AKT pathway. Furthermore, FAAs were capable of reduce the C6 migratory potential. In conclusion FAAs have a promising potential to treat glioma-type brain cancer.

Introdução: O sistema visual de roedores da Amazônia da subordem Hystrichomorpha
foi largamente descrito, mas pouco se sabe a respeito da topografia de células
ganglionares alfa, as quais apresentam função no processamento da visão de estímulos
em movimento. Os roedores cutia (Dasyprocta aguti), paca (Cuniculus paca) e capivara
(Hydrochoerus hydrochaeris) são três diferentes espécies de Hystrichomorpha que
apresentam ciclo circadiano e estilo de vida diferente. Objetivos: Quantificar a
densidade das células ganglionares alfa e analisar o tamanho do corpo celular de acordo
com a excentricidade na retina de cutia, paca e capivara. Métodos: Foram utilizadas três
retinas de cutia, de paca e de capivara provenientes da coleção histológica de retinas do
Laboratório de Neurofisiologia Eduardo Oswaldo Cruz da UFPA. Para a obtenção das
retinas, os animais foram anestesiados e sacrificados conforme as normas vigentes na
época da coleta. As lâminas da coleção foram coradas pelo método de Nissl e foi
realizada a contagem direta ao microscópio óptico Zeiss. Analisou-se a densidade de
células ganglionares do tipo alfa-like em diferentes excentricidades da retina, como na
faixa visual, area centralis, regiões dorsal e ventral. Resultado: Analisando a totalidade
da retina, a densidade média das células ganglionares alfa-like da cutia foi de 94,7±5,05
células/μm2 , da paca foi de 28,7±2,03 células/μm2 e da capivara foi de 101,03±24,42
células/μm2. Foi observada a presença de áreas com alta densidade de células
ganglionares alfa na região temporal da retina dos três roedores, sendo que a cutia foi a
espécie que apresentou a especialização mais acentuada desse tipo de células
ganglionares. A área do corpo celular das células ganglionares alfa que apresentou
maior frequência na retina da cutia foi o de 200 μm2, na retina da paca foi de 300 a 600
μm2 e na capivara foi de 300 a 500 μm2. Conclusão: Conclui-se que há uma relação

ix
entre a ecologia das espécies e densidade de células ganglionares alfa da retina dos
grandes roedores brasileiros, de forma que os que apresentam hábitos diurnos
apresentam retinas com maior número dessas células e com maior especialização na
região temporal.

The mammalian prefrontal cortex (PFC) is the cerebral cortex area involved in processing several functions as cognition and complex motor control for social interactions. In this PFC area, there is no duration of the time window definition about its critical period of plasticity. One of the potential biological markers for this may be the Perineuronal Nets (PNNs). The present work aimed to examine the developmental time course of PNN formation focusing on the medial prefrontal cortex (mPFC) of rats using histochemistry with Vicia villosa agglutinin. We use 21 male rats Rattus novergicus, wistar lineage, which were randomly divided into seven experimental groups, composed of 3 animals in each group, as follows: group at 7, 14, 20, 26, 58, 75, and 135 postnatal days, respectively. We  found that in PFC, PNNs appear at P26 with a small number of Vv+ cells, increasing in total numbers until adulthood. The results of the present study demosntrate the temporal development of PNN formation in the Wistar rats mPFC, and we suggest a time window for the end of the critical period of plasticity in this cortical area (26- 75 postnatal days), there is a progressive decrease in PNNs with immature profile and a concomitant increase in mature PNNs during postnatal development of the mPFC, making this PNNs profile more prevalent at more advanced ages, around 3 months of age, when the animals are already considered young adults.

Introduction: Binural Interaction (BI) allows the introduction of auditory information (in the brain as a function of differences in perception of intensity or time of acoustic stimuli). Allows you to assess the action and integrated co-operative of the brainstem in lower understanding. As the maturation of the central nervous system occurs in the craniocaudal direction, the response to this ability may change during the course of development. Objectives: To normalize and compare the development with increasing age of response in the binaural diffusion test (BPT) with digital low-pass (LP) and high-pass (HP) filters in normative listeners. Methods: Prospective, cross-sectional and observational study. A total of 120 years were evaluated, in different age groups (6 to 8 years old, 10 to 12 years old, 14 to 16 years old and 20 to 30 years old) with TFB, filter at Fc 500/1700 Hz digital Finite Impulse Response type order 4096, with null phase and 5000 between 18 and 30 years with unfiltered speech material. Results: a progressive improvement in performance with increasing age (ANOVA (one-way): p&lt;0.0001). There was a significant difference between the filtered words, age and the unfiltered p &lt; (Dunnet: any filtered words,01). The difference between the age groups was significant (Tukey: p&lt;0.01), less for the results obtained in the age groups of 6-8 and 10-12 years and of 14-16 and 18-30 years. Discussion: IB is a skill that evolves with age development and NC fabrication. Final considerations: The interpretation of the TFB should take into account the performance by age group of the patients. This is important for future applications of these tests in people with Auditory Processing Disorder.

Visual symmetry is almost universally present in both natural and artificial environments. Its importance is on both perceptual and cognitive levels. Symmetry processing, especially bilateral symmetry, is fast, efficient, and noise resistant. Humans, like other species, prefer symmetrical visual stimuli, a preference that is influenced by factors such as age, sex, and artistic training. In particular, artistic training in visual arts seems to decrease the rejection of asymmetry in abstract stimuli. But it is not known whether the same trend would be observed concerning concrete stimuli, such as human faces. In this work, the role of expertise in visual arts, music, and dance, in the perceived beauty and attractiveness of human faces with different asymmetries was investigated. With this objective, the beauty and attractiveness of 100 photographs of faces (50 male and 50 female) with different degrees of asymmetry were evaluated by 116 participants with different levels of art expertise. The art expertise in the three artistic modalities mentioned was assessed through an Arts Expertise Questionnaire. Facial asymmetry was obtained from geometric morphometric techniques in the MorphoJ software. Multilevel modeling strategies (ANOVA for repeated measures, correlation for repeated measures and linear mixed models) were used for statistical analysis. Expertise in visual arts and dance was associated with the extent to which facial asymmetry influenced the beauty ratings assigned to the faces. The greater the art expertise in visual arts and dance, the more indifferent to facial asymmetry the participant was to evaluate beauty. The same effect was not found for music and neither for attractiveness ratings. These findings are important to help understand how face aesthetic evaluation is modified by artistic training and the difference between beauty and attractiveness evaluations.

Sepsis is defined as a potentially fatal organ dysfunction caused by a dysregulated host immune response to an infection. During sepsis, dysregulation of the host response occurs with the excessive release of pro-inflammatory mediators, generation of reactive species with depletion of antioxidant defenses and cellular damage. As a result, the patient develops organ dysfunction. In this context, our group proposes the A.brasiliensis Lipid Fraction (FLAb) as a possible therapy for sepsis considering its immunomodulatory and systemic antioxidant activity in a murine sepsis model. Thus, the present study aimed to evaluate the activity of FLAb isolated in vitro and to evaluate the effect of treatment with FLAb alone or associated with the antibiotic ertapenem (F-Erta) on coagulation, antioxidant and immunomodulatory parameters in the lethal sepsis model in murine. For this, FLAb was kindly provided by Dr. Herta Dalla-Santa from UNICENTRO. In the present study, the antioxidant capacity of different concentrations of FLAb (1.25 and 5 μg/mL) was evaluated and in a RAW 264.7-Luc macrophage cell line, cytotoxicity, phagocytic capacity, nitric oxide, NF-κB activity and cytokines TNF-α and IL-6 were evaluated.The survival rates were analyzed 7 days in a model of CLP sepsis in swiss albino mice (Mus musculus), and treated with CLP+Salt (0.9%), CLP+FLAb (0.2mg/Kg), CLP+F-erta (0.2mg) /Kg; 30mg/Kg). For evaluation of on coagulation, antioxidant and immunomodulatory parameters, the mice were treated by 6 and/or 24h after CLP. In vitro, FLAb show antioxidant and anti-inflammatory activity in both concentrations. In vivo, all CLP+Salt animals died within a maximum of 48 hours while the FLAb and F-Erta treated groups survived the 7 days. During this period, clinical parameters of these animals were evaluated, the septic animals treated with saline showed piloerection, with little active level of consciousness and most of the time they were stopped in the cage, some of them had ocular secretion. In addition, animals treated with saline showed significant weight loss, reduced water and feed consumption resulting in death. The FLAb and F-Erta groups were active, with normal appearance, with normal breathing and heart rate, in addition to consuming water and food within normal limits. In the inflammatory site, peritoneal cavity, the treatment with FLAb showed an anti-inflammatory effect, decreased reactive oxygen species (ROS) and increased GSH antioxidant activity and protected from cell damage, maintaining neutrophil recruitment and nitric oxide levels (NO), reducing the bacterial load. Regarding coagulation parameters (platelet count, tp and ttpa), treatment with FLAb and F-Erta eliminated the bacterial load and protected the animals from tissue damage. In the liver, 6 hours after CLP the treatment  with FLAb and F-ERTA was observed in the biochemical parameters protective effect, in addition, it presented immunomodulatory, antimicrobial and antioxidant activity preventing liver damage. In the parameters evaluated in the heart, the treatment with FLAb and F-ERTA after CLP protected the animals from cardiac damage through immunomodulatory, antimicrobial and antioxidant activity. In this sense, FLAb alone showed promise as a treatment and/or adjunct in sepsis, in addition to preventing organic dysfunction in septic animals.

Cancer is one of the diseases that kill the most in Brazil, with alarming projections until 2030. In view of the problems related to cancer treatment, such as the compromise of healthy cells and, consequently, the presence of adverse effects, it is imperative to seek of alternative substances that may have antineoplastic effects and that are effective in the treatment of patients with this disease. In this way, the use of bioactive compounds has been widely used in the fight against neoplasms. Thus, the substance 1-deoxynojimyricin (1-DNJ) isolated from Bagassa guianensis may have great anticancer potential. In view of the problems related to cancer treatment, such as the impairment of healthy cells and, consequently adverse effects, it is necessary to search alternative substances that may have antineoplastic effects and they are effective in the treatment of patients with this disease. The objective of this study was to evaluate the effect of 1-deoxynojirimycin (1-DNJ) extracted from wood residue of the species Bagassa guianensis in different cancer cell lines to investigate possible antineoplastic actions in vitro using gastric adenocarcinoma and glioblastoma cancer cell lines. To do that, it was evaluated the effect of the substance 1-deoxynojirimycin on cell viability in vitro after 72h of treatment in cell lines ACP02 and A172. We also evaluated the effect of this bioactive compound on cell migration pattern, cell death by apoptosis and cell cycle changes using flow cytometry and reactive oxygen production. The results showed that 1-deoxynojirimycin makes a significant reduction in cell viability of cancer cell cultures in both glioblastoma (A172) and gastric cancer cell (ACP02) cell lines. The reduction in viability appears to be more effective in glioblastoma cell lines, with a common ic50 much lower when compared to other cell lines. We propose that the reduction in viability may be related to the decrease in reactive oxygen production in both lines after treatment with 1-DNJ. Besides that, 1-DNJ interrupts the cell cycle, prevents cell migration and induces necrosis-like cell death in the ACP02 lineage and apoptosis in the A172 lineage. Therefore, we suggest that 1-deoxynojirimycin may be an important and effective chemopreventive substance for the treatment of glioblastoma and gastric adenocarcinoma cancers.

Transcranial direct current electrical stimulation (tDCS) is a non-invasive neuromodulation technique used to promote improvement in clinical symptoms of neurodegenerative diseases. There is evidence that tDCS could modulate the psychomotor abilities of athletes, which are important for the performance of these athletes. Among the combat sports, judo and jiu-jitsu are two types that represent fighting sports with specific physical and cognitive demands. Thus, the aim of this study was to investigate the effects of a single stimulation in the M1 region (primary motor), on cognitive (anxiety, reaction time) and physical (strength, muscle power, flexibility) parameters in male and female athletes. federated of these modalities. For this purpose, the fighters were submitted to two experimental sessions of tDCS (sham and stimulated), in a cross over scheme to avoid the effect of the order of results, consisting of psychomotor evaluations using as metrics the jump against movement (SCM), Wells’ test , manual and scapular dynamometry, STAI and the TReaction software, all performed pre and post intervention with a-tDCS where the stimulated condition was delivered with anodic current at 2 mA for 20 minutes. There were no statistically significant differences between pre- and post-stimulation conditions (sham or stimulated) and in the percentage of difference between the two pre- and post-test conditions. This data showed the absence of effects of tDCS in the parameters and test used.

Introduction: Ethanol is a psychoactive substance, whose consumption causes cognitive impairment, emotional disorders and tissue damage to the central nervous system, such as oxidative stress, neuroinflammation, excitoxicity, etc. The management of damage induced by this drug, both in abstinence syndrome and alcoholism, is not well established yet, being based only on the treatment of symptoms, reinforcing the necessity the search for therapeutic inputs able of correcting broadest the changes provoked. Ganoderma lucidum is a species known for its multiple health benefits, including antioxidant, anti-inflammatory, antidepressant, sedative-hypnotic, among others properties. Thus, it is possible that preparations of this mushroom can reverse the damage resulting from ethanol consumption. Objective: This study aimed to investigate the effects of an aqueous extract of the mycelium of G. lucidum on changes induced by alcohol exposure in binge drinking. Material and Methods: Wistar rats (n=30) were exposed to 5 binges of ethanol (3g/kg/day; 20% w/v) and 24 hours after the last administration were treated with an aqueous extract obtained from the mycelium of the G. lucidum at a dose of 100 mg/kg for 3 days. Approximately 24 hours later, open field, elevated plus maze, forced swimming and inhibitory avoidance tests were performed, and the animals were subsequently euthanized for analysis of oxidative stress markers in the blood. Results and Discussion: The treatment reversed the changes induced by alcohol, namely the decrease in the total distance covered by the animals in the open field test, indicating an improvement in locomotor activity; the length of stay in the open arms in the elevated plus-maze, suggesting attenuation of the anxiogenic-like behavior; the latency time for descent from the safe platform in the inhibitory avoidance test, demonstrating improvement in short-term memory and learning, and also the immobility time in the forced swimming test, which suggests reversal of the depressive-like behavior. Regarding oxidative stress, malondialdehyde, glutathione and total oxidizing capacity levels were reduced by the extract, suggesting the reestablishment of the oxidative balance. Conclusion: Given these results, it can be inferred that G. lucidum can be used as an adjuvant in the management of disorders caused by alcohol, however care with the dose must be observed.

The Gymnotiformes (Neotropical electric fish) are widely distributed in Central and South America, with greater diversity and abundance in the Amazon Basin, being an extremely diverse order. Among these, the Brachyhypopomus genus (Hypopomidae), currently with 28 described species, has karyotype data available for eleven species. Their diploid number (2n) ranges from 36 in B. brevirostris to 44 in B. flavipomus females. The Archolaemus genus (Sternopygidae), which comprises a complex of six species, has no cytogenetic data published so far. Aiming to extend this cytogenetic information to help the cytotaxonomy and better identification of species, as well as to investigate the chromosomal rearrangements responsible for the intragenic karyotype variation, in this work we aim to study the B. brevirostris karyotype from two localities: Santarém – PA and Mamirauá, Tefé – AM, besides making the first karyotypic description of the species Archolaemus janeae sp. nov., analyzing individuals from two localities: Rio Xingu, Altamira - PA and Rio Tocantins, Santarém – PA. The results obtained so far for the species Brachyhypopomus brevirostris show 2n = 38, all chromosomes being acrocentric, with constitutive heterochromatin evidenced in the centromeric region of all the chromosomes, as well as small heterochromatic bands in interstitial and distal regions of some pairs, in the of Tefé region - AM and Santarém - PA. Fluorescent in situ Hybridization with 18S rDNA probe marked the distal region of the 19q chromosomal pair and the telomeric probe hybridized to the distal region of all chromosomes, with no interstitial signs for Santarém – PA and Tefé – AM samples. Archolaemus janeae shows 2n equal to 46, being composed of 4 chromosomes of two arms and 42 chromosomes acrocentric (2n = 46; 4m / sm + 42a), for the localities of Santarém - PA and Altamira - AP. The constitutive heterochromatin is evidenced in the centromeric region of all chromosomes, as well as small heterochromatic bands in interstitial and distal regions in some pairs. The 18S rDNA occurs in the distal region of the short arm of pair 2, the 5S rDNA occurs in 5 chromosomal pairs and the snDNA sequence U2 indicated multiple hybridization. No interstitial telomeric sequences were observed. The populations exhibit identical karyotypes, confirming to be a single species. We present the first U2 marker data for this family. These data are of great importance as a reference for future cytotaxonomic studies of the genus.

Gliobalstoma (GBM) is a tumor characterized by a high level of aggressiveness with a mean survival of only 14.6 months, originating from neural stem cells present in the central nervous system, with great histopathological and genomic diversity. The high rate of intratumoral heterogeneity in the GBM makes the diagnosis of the disease and the appropriate therapeutic intervention difficult. Mitochondria are cell organelles associated with the regulation of cell metabolism, redox signaling, energy generation, regulation of cell proliferation and apoptosis. Thus, the accumulation of mutations in mitochondrial DNA (mtDNA) plays an important role in the pathogenesis of GBM, favoring abnormal energy production through aerobic glycolysis and contributing to resistance to apoptosis and conventional radio and chemotherapy treatments. This scenario makes it necessary to introduce new lines of research that bring together technologies that enable a better analysis and understanding of the GBM carcinogenesis process, as well as the understanding of the action of pisosterol, a compound with anti-proliferative activity. Thus, the present work aimed to evaluate the mitochondrial integrity in four glioblastoma cell lines (AHOL1, U343MG, 1321N1 and U-87MG) treated and not treated with pisosterol at different concentrations (0.5, 1.0 and 1.8 µg/mL-1 ), based on the investigation of possible alterations in this genome. Six mtDNA genes (ND1, ND3, COI, COII, COIII, ATPase-6) were analyzed by Polymerase Chain Reaction (PCR), followed by automatic sequencing and subsequent analysis and comparison of the sequences obtained. The study revealed that treatment with pisosterol did not change the pattern of mtDNA changes in GBM cell lines. We identified alterations in the ND1, ND3 and COI genes. In the ND1, a non-synonymous transition at position 3547 (A→G) was observed, which causes the change of the amino acid isoleucine to valine, and a synonymous transversion at position 3552 (T→A). In ND3, two transitions were also identified, the first nonsynonymous located at position 10398 (A→G) and the second synonymous at position 10400 (C→T). In the COI gene a non-synonymous transition was detected at position 7196 (C→A). The most frequent alterations were those observed in mitochondrial complex I, which is suggestive of a possible hot spot for the analyzed GBM cell lines. Complex I is related to the maintenance of equilibrium levels of NAD+/NADH and ROS, with the generation of mitochondrial membrane potential and ATP production, therefore, its dysfunction is often the cause of mitochondrial disorders and diseases. The analysis of polymorphisms and alterations present in mtDNA in GBM samples is necessary so that patients can have a better prognosis and more efficient treatment, as these changes influence the cell phenotype.

All the functions of the endocannabinoid system (ECS) are not yet fully understood, however this system is known to have a neuromodulatory effect, essentially attributed to cannabinoid type I receptors (CB1R), which systemic activation induces psychoactive effects. In contrast, the immunomodulatory effect of ECS, attributed mainly to cannabinoid type II receptors (CB2R), has been demonstrated as an alternative treatment for several acute or chronic inflammatory diseases, including neurodegenerative diseases in animal models via chronic CB2R activation. However, the effects of this treatment are still unclear shortly after its administration. In this sense, we seek to investigate the effects of the acute-systemic treatment of β-caryophyllene (BCP), a phyto-cannabinoid agonist of CB2R in a murine model of neuroinflammation induced by LPS. We performed the open field test (OF) 2 and 4 h after the induction of sickness behavior by Lipopolysaccharide (LPS) and demonstrated that in animals pretreated with BCP, in the 2 h window, there was maintenance in the quality of movement in animals that received LPS without alteration in the induction of sickness behavior, and increased activity in the aversive region of the apparatus in animals that did not receive LPS. Indicating the immune and neuromodulatory effect of BCP. We also performed the Morris Water Labyrinth (MWM) test 24 h after inoculation of LPS, however it was not possible to discriminate changes in learning, howeverthe inoculated and untreated animals proved to be more likely to form spatial memory. Finally, we observed that pretreatment with BCP increases lipid peroxidation and nitrite concentration in the brain 2 h after LPS inoculation, thus suggesting an immediate increase in oxidative stress by acute treatment with BCP in neuroinflammatory models. Therefore, it is of fundamental importance to continue researching the immediate neurological and immunological effects of BCP treatment in healthy animal models and in neuroinflammatory models for better determination of the risks attributed to this treatment, as well as the addition of acute treatment to the detriment of the treatment. chronic in different neurological pathologies.

Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases, affecting about 2% of the world population. Some neuroinflammatory processes are associated with the causative (or consequential) factors of PD and neuroprotective drugs can be used as possible palliative treatments to delay the development of the disease. In this sense, one of the possible treatments is using oil-resin extracted from plants of the Copaifera sp. which already has an important ethnopharmacological role as an anti-inflammatory and, therefore, may have neuroprotective action. In the present study, we propose to evaluate the copaiba oil resin on cell viability in an in vitro rotenone-induced Parkinson's disease model and its possible cytoprotective effect. We used mixed primary cultures of cells derived from the ventral midbrain, mixed primary cultures of cells from the total cerebral cortex and mixed primary cultures of cells from the hippocampus of newborn rats. To mimic PD in vitro and cell degeneration, we used the rotenone intoxication model with 3-day exposure for ventral midbrain cultures and 24-hour exposure for cultures derived from the total cerebral cortex and hippocampus. We performed the concentration-response curve analysis for the oil-resin of Copaifera reticulata Ducke during 3-day exposure to ventral midbrain cultures. Finally, we carried out experiments of concomitant exposure to copaiba oil-resin and rotenone intoxication. We perform MTT assay to measure cell viability. Our results demonstrated that rotenone caused a reduction in cell viability at all concentrations of rotenone from all mixed primary cultures. In the concentration-response curve for the oil-resin of Copaifera reticulata Ducke, there was cytotoxicity at the highest concentrations tested for the mixed primary culture of ventral midbrain. When exposure to concomitant cell cultures to rotenone and copaiba oil-resin, the oil-resin was effective only for mixed primary cultures derived from the ventral midbrain and hippocampus of newborn rats and was not effective in protecting the cells of the mixed primary culture of total cerebral cortex cells against rotenone-induced intoxication. Our results showed that rotenone has a concentration-dependent deleterious effect, the oil-resin of copaiba has toxicity in concentrations greater than 10 µg/mL for cells from the ventral midbrain, whereas the oil-resin promotes neuroprotection against the deleterious effects of rotenone for the mixed primary cultures of the ventral midbrain (1 µg/mL) and mixed primary cultures of the hippocampus (25 µg/mL) and that for the mixed primary cultures of the total cerebral cortex the oil-resin was not capable of neuroprotection.

The loss of teeth and lack of oral hygiene have been associated with the risk of developing gastric cancer in several populations evidenced in epidemiological studies. In this study, we quantitatively compared the proportion of oral pathogens in individuals with gastric cancer and individuals without cancer in a referral hospital in the city of Belém, Brazil. This study evaluated 192 patients with gastric cancer and 192 patients without cancer. Periodontal clinical examination was performed, and all individuals were submitted to the collection of salivary and dental biofilms. When comparing the median periodontal indexesin the gastric and cancer-free groups, it was statistically significant in the gastric cancer group compared to the probing depth of the periodontal pocket. Levels of bacterial DNA were observed in saliva and dental plaque, with a statistically significant difference between individuals with cancer and without neoplasia in all the bacteria surveyed. Significant relationships between biological agents and gastric cancer have been found in bacterial species that cause high rates of periodontal pathology and caries. The results suggest a different quantitative association in the presence of oral pathogens between individuals without cancer and patients with gastric cancer. As noted, it cannot be said that the bacteria present in the oral cavity increase the risk of gastric cancer or are aggravating factors of the disease. However, it is worth mentioning that, as it is part of the digestive system, the lack of care for the oral cavity can negatively affect the treatment of patients with gastric cancer.

Introduction: Schizophrenia is a serious and complex pathology that affects about 0.5-1% of the world's population, is chronic in nature, and is recognized as one of the 15 leading causes of disability. For the clinical diagnosis of schizophrenia, there are clinical criteria to be evaluated, which include both positive and negative symptoms. There is a genetic predisposition and its manifestation occurs after exposure to environmental stimuli. Thus, strong evidence shows that these environmental stimuli have the ability to act on epigenetic mechanisms that act in the regulation of gene expression. MicroRNAs (miRNAs) are stable and potentially reliable biomarkers, and some miRNAs have been previously identified as potential biomarkers for schizophrenia in peripheral samples. Objective: To evaluate the expression profile of circulating miRNA's in patients with schizophrenia (hsa-miR-34a, miR-449a, miR-564, miR-432, miR-548d, miR-572 and miR-652) in relation to control individuals negative for the disease. Methods: Analytical, case-control, cross-sectional study using samples previously collected from patients diagnosed with Schizophrenia (N = 650) and control group (N = 924), who adequately met the inclusion criteria. The samples were analyzed after RNA extraction through its quantification and techniques for obtaining reverse transcriptase reaction and real-time quantitative polymerase chain reaction. All data were analyzed using the IBM SPSS22 statistical program. Conclusion: Using the peripheral blood collection method with the intention of finding possible biomarkers for schizophrenia, an increased expression of the seven miRNA's was observed in several analyzed scenarios, showing potential diagnostic value.

Keywords: Schizophrenia; microRNA; Mental health; Biomarkers; Epigenetics.

The non-steroidal anti-inflammatory drugs are among the most used and prescribed in the world, however this type of drug has several side effects at the neural level. Studies related to neurobehavioral and neurochemical damage of this class of drug are still necessary for a better understanding of all the possible damages that they can cause. As a result, indomethacin, which is an NSAID, has been widely used to treat pathologies such as rheumatoid arthritis, musculoskeletal injuries, osteoarthritis and postoperative pain. Indomethacin non-selectively blocks the enzymes COX-1 and COX-2, acting to decrease the production of prostaglandins. Therefore, this study proposed that the indomethacin could be generated anxiogenic effects and oxidative stress in the brain, and whether the antioxidant α-tocopherol exercised protection against the possible damage caused by indomethacin in zebrafish. The animals used were fish of the species Danio rerio (n=160), subdivided into the following groups: Control - Saline 0.9%; Indomethacin - INDO 0.5 mg/kg; INDO 0.75 mg/kg; INDO 1.0 mg/kg; INDO 2.0 mg/kg; INDO 3.0 mg/kg; α-Tocopherol - TF; TF + INDO 1 mg/kg; TF + INDO 2 mg/kg and were subjected novel tank diving test, the parameters time on top, freezing, erratic swimming and crossed quadrants were analyzed. The statistical analysis of the results was performed using one-way ANOVA with a post-test bonferroni or tukey for comparison between groups, with values with p <0.05 being considered significant. The results regarding the behavioral parameters and oxidative stress were expressed as mean ± standard error or standard deviation. The parameters that showed statistical differences were the time at the top and freezing, where the animals of the groups INDO 0.5 mg/kg, INDO 0.75 mg/kg, INDO 1 mg/kg and INDO 2 mg/kg explored for less the top of the apparatus compared to the CTRL group. In the freezing parameter the groups treated with indomethacin INDO 0.5 mg/kg, 0.75 mg/kg and 2 mg/kg did not show statistical differences with the CTRL group, however there was a difference between the CTRL and INDO groups 1 mg/kg. In the freezing parameter, the animals in the INDO 1 mg/kg group showed a longer time without movement compared to the CTRL group. In the other parameters, there were no significant differences between the groups treated with the control group. The analysis of lipid peroxidation, the INDO 1 mg/kg and INDO 2 mg/kg groups showed an increase in MDA production compared to the CTRL group, thus inferring that there was an increase in oxidative stress when animals were treated with indomethacin. The α-tocopherol exercised protection when animals were previously treated in both the TF + INDO 1 mg/kg group and the TF + INDO 2 mg/kg group compared to the INDO 1 mg/kg and INDO 2 mg/kg groups, respectively. Therefore, indomethacin is involved in inducing anxiety- like behavior and oxidative stress in zebrafish brains.

Keywords: NSAIDs; indomethacin; anxiety-like behavior; oxidative stress; zebrafish.

The anxiety disorders are related to dysfunctional defensive behaviors. Serotonin (5-HT) modulates these defensive reactions, increasing anxiety-type conflict responses through action in prosencephalic structures and inhibiting escape/panic-type physiological and behavioral responses through action on mesencephalic structures. Evidence of a dual role of serotonin on the regulation of defensive behavior has also been found in zebrafish. The purpose of this work was to evaluate the involvement of the 5-HT2C serotonergic receptor in the zebrafish alarm reaction triggered by the exposure to the alarm substance (AS). Alarm reaction is a set of adjustments neurobehavioral behavior characterized by an increase in the time the animal spends at the bottom of the aquarium (geotaxis), an increase in the frequency of erratic swimming and freezing behaviors and the production of an intense autonomic response. Additionally, the acute restraint stress (ARS) protocol was used to investigate the participation of the 5-HT2C receptor in the response to restrictive stress. Before being subjected to stress protocols, the animals were pre-treated with selective 5-HT2C receptor agonist - MK212. The results revealed an increase in geotaxis, erratic swimming, and in the duration of freezing during exposure to the alarm substance. After exposure, AS increased the duration of freezing. The ARS decreased the time at the top of the aquarium and increased geotaxis, erratic swimming, and the freezing duration. Pretreatment with MK212 (2 mg/kg) blocked the increase in geotaxis and erratic swimming during exposure to the alarm substance. After exposure to SA, treatment with MK212 (1 mg/kg) decreased the duration of freezing. MK212 (2 mg/kg) blocked the increase in the duration of freezing after the ARS. The results demonstrate that the activation of 5-HT2C receptors partially blocks the alarm reaction of the zebrafish (panicolytic-like effect) and blocks the increased freezing in the DVEN test. Together, these findings suggest that the 5-HT2C receptor selectively participates in neurobehavioral responses in zebrafish and is more strongly involved in panic-related defensive reactions.

Speech understanding requires constant reconstruction by the central nervous system of sound signals corrupted by environmental sounds, a central auditory processing skill known as auditory closure. Currently, in Brazil, to evaluate this ability, testing with monosyllables analogously filtered, which has a restricted speech material and a limited attenuation of the acoustic components, not adequately forcing the nervous system to recompose the original message. The objective of this thesis was to evaluate the ability to perform auditory closure using speech material with significant content, the extrinsic redundancy of which is effectively reduced through digital filtering, both in the frequency range and in the intensity of sound attenuation, in order to improve the detection of central nervous system failures to understand the original message. A cross-sectional and prospective study was carried out. Initially, words with significant content, used in literacy, were selected based on verification of comprehension by healthy children. After the selection, this speech material was digitally filtered at various low-pass and high-pass cut-off frequencies and listened to by normal hearing adults, to establish the appropriate cut-off frequency for testing. The two new filtered speech tests were applied to children and adolescents of different age groups to determine how age affected performance, and in children with auditory processing disorders, before and after acoustically controlled auditory training to assess diagnostic capacity and clinical improvement after treatment. There was a progressive increase in performance with less restrictive filters (p <0.001) and with increasing age for all tests (p <0.001). The auditory closure for low-pass filtering matured earlier than with highpass filtering. It has been shown that the new tests can also be used to diagnose changes in auditory processing and to evaluate functional improvement after auditory training. These tests enhance the current diagnostic tools to assess auditory closure, providing information on its maturation during normal development, validating this method for diagnosis and for control after treatment of patients with auditory processing disorders.

The homeostatic state of an organism is constantly subjected to stressful situations, which can change according to its nature and duration. The stress response refers to the response of a subject to these stressful stimuli, resulting in several physiological adaptations that can lead to behavioral changes and trigger neurobehavioral disorders, such as anxiety disorders. Among the changes that occur in the organism due to the anxiety-like behavior induced by stress, we highlight the generation of reactive oxygen and nitrogen species. In this sense, nitric oxide (NO) plays an important role in the adaptive response of the organism, since exposure to stressors modifies its production. However, the data regarding the role of NO in stress-induced anxietylike behavior is not fully understood. Thus, we aim to demonstrate pharmacologically the participation of the nitrergic system in the generation of anxiety-like behavior induced by acute restraint stress (ARS) in Danio rerio (zebrafish). For this, 92 adult fishes of the specie Danio rerio (zebrafish) were used and divided into the following groups: control (saline 0,9%), ARS, L-NAME (10 mg/kg) and L-NAME+ARS. The ARS protocol consisted in keeping the animals under restraint in microtubes for 90 minutes. Subsequently, anxiety-like behavior was assessed in the Novel Tank Diving Test and, right after, the brains were collected to quantify lipid peroxidation. Data were analyzed by two-way ANOVA, followed by Tukey post-hoc, considering statistical difference when p<0.05. Our results demonstrated that the exposure to ARS had an anxiogenic effect on the behavior of the animals tested in the Novel Tank and raised the levels of lipid peroxidation in the brain of zebrafish. On the other hand, pre-treatment with NOS inhibitor (L-NAME) prevented those changes in behavior and lipid peroxidation induced by ARS. Then, we conclude that the activation of the nitrergic pathway play a role in the generation of anxiety-like behavior induced by ARS.

Autism Spectrum Disorder (ASD) is a disorder manifested by deficiencies in the conditions of neurodevelopment and characterized by severe impairment in reciprocal social interactions and communication skills, in addition to the presence of stereotyped behaviors. Prenatal exposure to valproic acid (VPA) in mice has been widely used as a model of inducing behaviors similar to autism associated with cellular changes. However, no study has reported the influence of exposure to VPA in utero, in tasks dependent on the hippocampus and on the microglial response in the lateral septum (SL) in adult female mice. Thus, the aim of this study was to investigate behavioral and microglial changes in the lateral septum in a murine model (Balb / c) of ASD, induced by exposure to valproic acid in the gestational period, compared to control animals. Female mice (Mus musculus), of the BALB / c strain, received, on day 12.5 of gestation, a single dose of oral solution of sodium valproate diluted in saline (600 mg / kg by body weight), or an equal volume of solution saline. The offspring were organized in standard laboratory cages on the 21st postnatal day. After 5 months of age the females were subjected to behavioral tests, and then the processing of their brains for selective microglial marker (IBA-1 antibody). The analysis of the open field tests (distance covered, immobility, crossed lines and occupation index of the periphery vs. center), elevated maze in the cross (distance covered, immobility and occupation index of closed vs. open arms) and microglial quantification and volumetric showed significant differences between the VPA and control groups, (two-tailed t test, p ≤ 0.05). The results showed that female mice exposed to valproic acid during pregnancy showed significant losses in their exploratory behavior in adulthood. We suggest that these behavioral changes are associated with the central inflammatory response triggered by VPA. We infer that this gain may be related to the behavioral changes found, which are similar to those observed in autism.

Meningiomas correspond to more than a third of primary neoplasms of the Central Nervous System (CNS), being the most common intracranial tumor. They are mostly benign, slow-growing, affecting twice as many women as men. Studies of quantitative genomic changes in tumor samples allow the performance of correlative analyzes, with possible identification of diagnostic and prognostic biomarkers of these pathologies. Thus, the present study aimed to analyze the occurrence of changes in the number of copies (CNAs) in 33 samples of meningiomas collected from patients in a population of Belém-PA, through the application of aCGH. According to histopathological classification, the samples were divided into twenty-six grade I samples, 9 meningothelial, 5 fibroblastic, 4 transitional, 2 psamomatous, 3 mixed, 1 syncytial, 1 microcystic and 1 hemagioblastic. Two grade II samples being of the clear cell subtype and one grade III sample of the anaplastic subtype. The study revealed that the proportion of women affected in relation to men was 3: 1. The aCGH analysis showed a total of 2,304 CNAs with an average of 69.8 ± 57.4 per case, of which 1,197 were won (52%), 926 were losses (40.2%), 105 were amplifications (4.5 %) and 76 were deletions (3.3%). A significant relationship was observed between the type of ANC and the degree of the tumor (χ2 = 65,844; p <0.0001; contingency coefficient: 0.1772; p <0.0001). Taking into account all the CNAs found in the study, when comparing samples belonging to the three degrees of malignancy, we identified changes in most of the chromosomes, with some being present in the three histopathological degrees, such as losses in 1p, 10q, 14q, 22q and gain in 14q. Others were present in grades I and II, such as gain in 5p, 9q, 16p, 17p and 17q. Alterations present only in grades II and III, such as loss in 3p, were also identified. The analysis of these regions showed the compromise of genes with functions such as regulation and maintenance of cell survival, reorganization of the cytoskeleton, cell signaling and DNA repair, among others. An interesting finding was a recurrent gain of 8p22 seen only in grade I meningiomas, a region that includes DLC1, a candidate suppressor gene, probably implying the development or progression of meningiomas, usually found deleted in other tumor types. Thus, our findings infer about a specific pattern of changes in the studied population, suggesting a specific pattern for the appearance and progression of these tumors. Key Words: Meningioma, aCGH, CNAs, DLC1.

Environmental pollution is one of the consequences of large-scale industrialization, due to the dumping of chemicals and other wastes, especially in water bodies. A prominent place is occupied by heavy metals, due to the large quantity in industrial waste and harmful effects to health. Among these, we highlight mercury (Hg), used in the extraction of gold in clandestine gold mining and discarded in rivers, and lead (Pb) used as a container for radioactive agents, in water pipes, in cable coverings. Many human populations are exposed to sublethal doses of these pollutants, with no acute effects. However, in organisms, heavy metals can accumulate and affect systems, organs and cellular components, including interactions with DNA and certain nuclear proteins, causing damage and conformational changes in the genetic material, which can lead to apoptosis, changes in the cell cycle, and to carcinogenesis processes. Considering that in vitro studies provide important information regarding the interactions of substances and cell components, our study analyzed the cytotoxic and genotoxic effects of sublethal concentrations of mercury and lead in human fibroblasts. In addition, the results were analyzed by different methodologies in order to analyze their efficiency and complementarities. For this, a fibroblast secondary cell line, not transformed, was exposed to three different sublethal concentrations (5, 10, 15 µM) of MeHg and Pb(NO3)2 for 30 minutes. Cytotoxicity and viability were analyzed using protocols based on membrane damage test (Trypan Blue), transformation of resazurin into resorufin, and protease activities. In addition, we performed the MTT test. Genotoxicity was analyzed using the micronucleus test and the comet assay. The results of the Trypan Blue and tests based on protease activities showed that all concentrations showed cytotoxic effects, with significant p value, while the test using resazurin showed cytotoxic activity only in the two highest concentrations. This difference may be due to the influence of cell number in the results of this technique. Results obtained using the MTT test did not agree with the other viability tests, but could be interpreted as alterations in cell metabolism, confirming recent reports. Micronucleus test and Comet assay indicated both metals are genotoxic. MeHg showed a higher frequency of micronuclei in relation to Pb (p <0.001), but there was a higher number of apoptotic nuclei in cells treated with Pb, which may indicate that the concentration used was more cytotoxic than MeHg, and a lower number of cells completed the cycle in order to produce micronuclei. In the comet assay, which is done right after the exposure period, both metals produced DNA fragmentation, with a slightly higher value of breaks by Pb. We conclude, therefore, that mercury and lead are cytotoxic and genotoxic even in sublethal doses. Concerning the different protocols, Trypan blue, although simple, is a good indicator of cell viability, while MTT behaved clearly as an indicator of general cell metabolism, and should not be used as a viability test. The use of different tests was relevant to a better understanding of the mechanisms of aggression of heavy metals to cells, bringing preliminary evidence about the effects on human health, as well ecological damages.

The use of drugs of abuse is a worldwide public health problem. Alcohol is often used in combination with other drugs, including ketamine. Little information is available about the damage caused by this association. The aim of this study was to investigate changes in emotional behavior and oxidative stress in the prefrontal cortex and hippocampus caused by the consumption of ketamine associated with ethanol in female rats in their adolescence. Four groups of adolescent rats (n = 10 animals per group) were used, with 28 days of life, divided into control (saline intranasal, + distilled water via gavage), CET (10 mg/Kg intranasal), EtOH (3 g/Kg via gavage), CET + EtOH (10 mg/Kg intranasal + 3 g/Kg via gavage). The administration was carried out for 3 consecutive days. The animals were evaluated twenty-four hours after the last administration. The battery of behavioral tests consisted of open field, elevated plus maze and forced swimming. After the behavioral tests, the prefrontal cortex and hippocampus were collected to evaluate ROS, ACAP and LPO. The results obtained in the open field test demonstrated preserved spontaneous locomotion and anxiety-like behavior in the CET + EtOH group, with no differences with the isolated drugs, a result confirmed with the elevated plus maze. In the forced swim test, the CET + EtOH group demonstrated depression-like behavior, similar to the isolated drugs. In the evaluation of oxidative biochemistry, the CET + EtOH group demonstrated an increase in ROS production similar to the CET group in the hippocampus. In the prefrontal cortex, the increase in ROS production in the CET + EtOH group was higher than the EtOH group and lower than the CET group, but there were no changes in ACAP and in the levels of LPO. With these results it can be concluded that the combination of Ketamine and Ethanol induces anxiety and depression behaviors, similar to isolated drugs, with increase in ROS production in the prefrontal cortex and hippocampus.

Background: Schwannomas are benign tumors, with slow growth, generally encapsulated, which originates from nerve’s myelinated sheath. They may occur associated with several genetic disorders, in special the Neurofibromatosis type 2, where the diagnosis of Bilateral Acoustic Schwannoma is a diagnostic criteria. When they occur in the spinal compartment under the Magnum foramen, they are denominated Spinal Schwannomas. Objective: To determine the frequency of gene NF2’s heterozygosity loss in patients with Sporadic Spinal Schwannomas. Method: In this study there were included 39 patients from both genders, attended in Neurosurgery Services located at hospitals in the north of Brazil, with the diagnosis of Spinal Schwannomas, from January 1990 to December 2013. In all patients it was performed Immunohistochemistry Test of S-100 protein. It was realized the extraction and amplification of DNA from paraffin blocks of patients diagnosed with Schwannoma. As a standard technique to evaluate mutational status and also to verify the heterozygosity loss it was done the I- FISH. Results: The average age of patients at the time of diagnosis was 48,82 years; of which 18 were women and 21 were men. The mean time interval from the presentation of first symptoms and the diagnosis was 14,05 months. The patients presented overall survival and progression free survival of 100%. Point mutations and/or loss of alleles were identified in 16/39 samples (41,03%). The LOH highlighted by alleles’ deletion and/or mutation of the other allele, was observed in 7/28 tumors (17, 94%). Two homozygous mutations (with the presence of both alleles) were detected in 4/39 tumors (10, 25%) and the presence of heterozygous mutations, which means in the presence of two alleles, was revealed in 3/39 (7,69%). In 2 tumors it was identified the loss of one NF2’s allele without the presence of mutation. It was detected no aberration in gene NF2 in 23 schwannomas (58,97%).
Key-words: Spinal Schwannomas; gene; NF2; mutation.

Rodents is an order of mammals highly described with the largest number of species, having extremely varied habitat. It occurs in various types of environments with wide geographic distribution, absent in Antarctica. One of the probable reasons for Rodent's evolutionary success is due to its wide variety of foods. Cricetidae is one of the families of this order, which is inserted in the subfamily Sigmodontinae. This subfamily is mainly represented by rodents from South America, and among them there are species of the genus Cerradomys, grouped in the Oryzomyini tribe, which covers about 35% of sigmodontine rodents. Rodents have a high karyotype diversity, with a number ranging from 2n=10 in Ctenomys steinbachi (Family Ctenomyidae) and Akodon sp. (Family Cricetidae) at 2n=102 in Tympanoctomys barrerae (Family Octodontidae) and 118 in Dactylomys boliviensis (Family Echimyidae). A more recent classification considers that the genus Cerradomys has eight species, all with basic characteristics used. The number varies from 2n=46 in Cerradomys langguthi to 2n=60 in C. akroai, that is, there may be a high number of chromosomal rearrangements. Here we studied by classical cytogenetics (C- and G-banding) and by chromosomal painting with probes of total chromosomes of Hylaeamys megacephalus (HME; 2n=54), the karyotypes of three species of Cerradomys: C. scotti (2n=58), C subflavus (2n=54) and C. vivoi (2n=50) and compared with C. langguthi, described in the literature, diagnosing the possible chromosomal rearrangements that occur during a karyotype evolution, of the species of this type. A comparative analysis was performed with the Sigmodontina species already mapped with HME probes, or that demonstrated the C. langguthi karyotype, in relation to H. megacephalus, more rearranging when C. scotti, C. subflavus and C. vivoi. In addition, we found that C. vivoi shares more conserved syntheties with C. langguthi than C. scotti and C. subflavus, compared phylogenetically, or that they are reinforced by the presence of four synthetic blocks conserved in the different analyzed, or that they can be executed partly of the ancestral genome of the genus.
Keyword: Cytogenetics; Synthetic blocks; Chromosomal rearrangements.

Astrocytes are essential for lipid neuronal metabolism in long-distance
uninterrupted migratory flights, when glucose is not available as the main source
of energy. We previously demonstrated in Calidris pusilla that after uninterrupted
5 days transatlantic flight, astrocytes shrink and reduce its number in the
hippocampal formation. Here we shifted our attention to the wintering period and
tested the hypothesis that as the wintering progresses, hippocampal astrocytes
morphological changes following Atlantic crossing, would be recovered. To that
end we used Arenaria interpres, which also crosses the Atlantic Ocean and
reaches the mangroves of the Amazon River estuary for wintering. Birds were
captured in September/October (closer to the arrival in the coast of Bragança -
Pará, Brazil for wintering) and in April/May (closer to the departure towards the
breeding sites) and had their brains processed for selective GFAP-astrocyte
immunolabeling. Three-dimensional reconstructions of the immunostained
astrocytes were performed and morphological classification was done based on
hierarchical cluster and discriminant analysis of multimodal morphometric
features. We found two morphological phenotypes of astrocytes exhibiting
distinct morphological complexities after the long-distance non-stop transatlantic
flight. Although to a different extent, both morphotypes increased their
complexities as wintering period progresses towards the pre-migration window.
Taken together, our findings demonstrate that the long-distance non-stop flight
and wintering period differentially affected the two astrocytes morphotypes,
suggesting distinct physiological roles for these cells. We suggest that
morphological recovering during the wintering period, may be part of the adaptive
changes of the local hippocampal circuits of A. interpres in preparation for the
long journey back to their breeding sites in the north hemisphere.

We investigated long-term environmental influences on hippocampal-dependent tasks and the morphology of the outer and middle thirds of the molecular layer of the dentate gyrus (DG-Mol), the main targets of perforant pathways, in relation to object recognition and spatial memory. Twenty-month-old female, albino Swiss mice were housed from weaning in a standard (SE) or enriched environment (EE) and tested for object recognition and spatial memories. All mice could distinguish familiar from novel objects. However, SE mice could not distinguish stationary from displaced objects and spent two more training days in the water maze to learn the task. After testing, mice were sacrificed, and hippocampi were sectioned and processed for immunolabeling for IBA1, a selective microglia marker. Random and systematic microglia samples were reconstructed in three dimensions and classified using hierarchical cluster analysis. SE mice showed two morphological phenotypes of microglia in both the outer and middle thirds of DG-Mol. EE mice showed such a reduction in the morphological diversity of microglia that essentially a single morphotype was found. Because EE mouse microglia showed an intermediate morphological complexity between types I and II SE microglia that was associated with higher performance in spatial memory and learning, we infer that morphological complexity might be an accurate indicator of homeostatic microglia. We also suggest that type I and type II microglia in SE mice may have different physiological roles and that the memory benefits of long-term EE may be associated with homeostatic adaptive responses of microglial phenotypes to somatomotor and cognitive stimuli.
Keywords: environmental enrichment, exercise, microglia morphology, spatial memory, learning, molecular layer, dentate gyrus.

Since their discovery, telomeres and telomerase have been the subject of intense research, first as a mechanism of cellular aging and later as an indicator of health. By protecting the ends of chromosomes, telomeres play a vital role in preserving information in our genome. Telomeres decrease with age, and their erosion rate of telomeres provides information on the history of cell proliferation in a tissue. The telomerase enzyme restores telomere size and plays an important anti-aging role. Telomere shortening is observed in many human diseases, including atherosclerosis, cancer, aging syndromes, schizophrenia, Alzheimer's disease, and vascular dementia. Major depression (DM) is a serious nosological entity, considered a public health problem and is commonly associated with chronic medical conditions and higher prevalence in senescence, suggesting a strong association with cell aging. Most analyzes published in the literature have shown an association between DM disorder and decreased telomeric function and telomere size, but there are other studies with conflicting results. For this reason, we analyzed telomerase expression and telomere size in peripheral blood leukocytes of 12 DM patients before and after treatment with sertraline antidepressants and / or escitalopram and compared these findings with those found in a control group. negative, composed of healthy individuals, and with a positive control group formed by patients with schizophrenia (ESQ). Analysis of hTERT mRNA expression, the catalytic subunit of human telomerase, was performed by quantitative real-time Polymerase Chain Reaction (qPCR) and Southern Blot methodology was used to analyze telomere length. Pre-treatment DM patients and ESQ patients had significantly lower telomerase expression and telomere length compared to the negative control (p <0.05). After treatment with the aforementioned antidepressants, DM patients had these two telomeric parameters increased and the statistical analysis showed no difference in relation to the negative control (p> 0.05). The recovery of telomeric function after treatment was accompanied by a 50% or more positive response in the clinical condition of DM patients. On the other hand, significance was observed in the difference in telomere size of negative controls and DM patients after treatment in relation to the group of ESQ patients (p <0.05). We can conclude that DM disorder has as a trigger or consequence telomere dysfunction and peripheral blood leukocytes may reveal activation of senescence pathways. Sertraline and / or escitalopram are highly effective in recovering the clinical picture and basal telomeric activity in DM disorder compared to the telomeric responsiveness of specific treatment for ESQ patients, known to have a more severe, chronic and deteriorating mental pathology. The positive outcome of DM patients, who after the beginning of treatment had recovery of telomeric parameters, reveals that telomere analysis is a potential tool for therapy monitoring and follow-up of patients who have their medication suspended due to clinical improvement. Following the patients in this study and increasing the sample number will allow us to see if symptomatic remission will be followed by total telomere recovery and maintenance of its basal function. A very important data not only for the therapeutic plan, but also for the prognosis of those affected by DM.

Mercury chloride (HgCl2) is a pollutant widely found in the environment. This form of mercury is able to promote several damages to the Central Nervous System (CNS), including changes to the motor cortex, an area related to the planning and execution of motor activity. However, the effects of HgCl2 on the spinal cord, an important pathway for the communication between the CNS and the periphery, are still unknown. We exposed adult rats for 45 days to HgCl2, orally, to investigate the effects on oxidative biochemistry, proteomic profile, and spinal cord structures. Our results showed that exposure to this metal promoted increased levels of Hg in the medullary parenchyma, impaired oxidative biochemistry, changes in antioxidant system proteins, energy metabolism and myelin structure; as well as caused disruption in the myelin sheath and reduction in neuronal density. Thus, we conclude that prolonged exposure to HgCl2 triggers biochemical changes and in the expression of several proteins, resulting in damage to the myelin sheath and reduction of neurons in the spinal cord, which may be related to motor damage.

Gastric cancer is one of the most incident types of cancer worldwide and presents high mortality rates and bad prognosis, especially in developing countries like Brazil. MYC proto-oncogene has been extensively investigated in cancer research due to its essential role in many different cellular activities, especially to those associated with cell cycle control. Its protein is an important transcription factor responsible for regulating the expression of a considerable part of the human genome. Moreover, MYC deregulation is one of the most commonly described phenomena in gastric carcinogenesis. It is well known that MYC positively regulates CDC25B expression which, in turn, regulates the cell division cycle progression inducing the cell to entry into mitosis. Constitutive activation of CDC25B can promote disorderly cell growth and proliferation and has been described in a wide variety of tumors, including gastric cancer. Herewith, specific inhibitors of CDC25B may be valuable in the treatment of stomach tumors. Menadione is a synthetic form of vitamin K that acts to inhibit the CDC25 family of phosphatases expression. Also, recent studies have shown that this compound can inhibit proliferation and induce apoptosis in different types of cancer cell lines. To better understand the menadione mechanism of action in gastric cancer, we evaluated its molecular and cellular effects in AGP01, ACP02, and ACP03 cell lines and in Sapajus apella, nonhuman primates from the new world which had gastric carcinogenesis induced by NMethyl-N-nitrosourea. In our in vitro experiments, we evaluated the menadione capacity of inhibit CDC25B expression, by RT-qPCR and Western blot, and, in addition of the cell cycle analyzes by flow cytometry, we investigated its potential to reduce proliferation, migration and invasion rates. In our in vivo tests, in addition to the CDC25B gene expression analyses, we followed the pre-neoplastic lesions and the tumor progression by ultrasonography, endoscopy, biopsies, histopathology, and immunohistochemistry. Our results demonstrated menadione inhibiting CDC25B expression in vivo and in vitro. It was able to reduce migration, invasion and proliferation rates, and induce cell cycle arrest in the gastric cancer cell lines. Furthermore, our in vivo experiments demonstrated menadione inhibiting tumor development and progression and promoting tumor shrinkage. Therefore, we conclude that CDC25B has proven to be an attractive target for investigation and development of new therapeutic strategies against gastric cancer, and suggest menadione may be an important ally of chemotherapeutics in the treatment of this malignancy. Key Words: Gastric cancer, MYC, CDC25B, menadione, Sapajus apella, N-Metil-Nnitrosourea.

Background: Depression is a mental disorder than become important on nowadays and is the most common disease causing disability. This mental disorder typically presents in adolescence or early adult life as well as elderly, where there are clinical reports of possible changes in the somatosensory and neurocognitive system. The aim of this study was to evaluate the sensibility perception in depressive patients compare to healthy participants using the techniques of mechanical, thermal, tactile and pain threshold. The way the study was performed in 25 patients diagnosed with depression (F.33) and 25 healthy controls, were realized the mechanical, thermal, tactile and pain threshold. Data revealed that the mechanical threshold was statistical significantly in the esthesiometer monofilament of 0,2g showing a sensory dysfunction of radial nerve of the left hand compared depressive patients with the healthy controls (1, 36 ± 0,098 vs. 1, 08 ± 0,055). In addition, we observed a sensory dysfunction of fibular nerve and sural nerve of right foot (0, 32 ± 0,478 vs. 0, 61 ± 0,495). Additionally, in the 2g and 4g was significant for a sensory dysfunction of the right foot compared depressive patients with the healthy controls (0, 25 ± 0,452 vs. 0, 58 ± 0, 50) and (0, 29 ± 0,470 vs. 0, 61 ± 0,496), respectively. On the other hand, tactile sensitivity in depressed (36%) and healthy patients (4%). However, for the other test of thermal and painful sensitivity, the results were not significant. These data suggest the occurrence of a dysfunction in peripheral nerves in upper limb of the radial nerve, also a dysfunction of lower limbs in fibular nerve, sural nerve and tibial nerves, which are the main branches of the sciatic nerve.

The brain continuously conveys signals to the viscera via interoceptive signals to establish homeostasis. Understanding how these signals are processed, as well as the underlying neurovisceral interaction, may help to elucidate their influence on cognitive and emotional processes under normal and pathological conditions, such as epilepsy. Epilepsy is a chronic brain disorder characterized by hypersynchronization of neuronal groups. Approximately 30% of individuals with epilepsy are refractory to pharmacological treatment. Even though the mechanisms underlying refractoriness are not yet understood, hypotheses to explain the possible causes have been proposed. According to the neural network hypothesis, the seizure-induced plastic remodeling of neural circuits may contribute to the formation of abnormal neural networks that suppresses the inhibitory effect of the endogenous antiepileptic system and also prevents Anti-Epileptic Drugs from reaching their targets. Therefore, seizures alter the dynamics of cortical neural networks. However, these changes are not restricted to the Central Nervous System, they also modify the activity of the Autonomic Nervous System and compromise cardiac function. The aim of the present study was to verify the interaction between the cerebral cortex and the cardiac autonomic system through the spectral and temporal evaluation of the correlation of electrophysiological activity in individuals with refractory epilepsy and a control group. The measures used were the average power of the cortical electrical signal in different spectral ranges of the EEG, the Heart Rate Variability (characterized by the parameters RMSSD, SD1, SDNN), and the Cardiac Evoked Cortical Potential (HEP). The results showed a significant correlation (p<0.05) between the theta average power and RMSSD, SD1 in the frontal, central, temporal and occipital regions. The theta average power showed a significant correlation with SDNN in all regions in epilepsy patients. HEP analysis indicated differences (p = 0.05) in latency in different time windows between the groups in the channels: Fpz, Fz, F8, F4, F3, Cz, C3, Pz, P4, T3, T4, T6 and O1. Our results show a differentiated dynamic coupling between cortical and cardiac activity in patients with refractory epilepsy.

Little is known about environmental influences on radial glia–like α cells (radial astrocytes) and their relation to neurogenesis. Because radial glia is involved in adult neurogenesis and astrogenesis, we investigated this association in two migratory shorebird species that complete their autumnal migration using contrasting strategies. Before their flights to South America, the birds stop over at the Bay of Fundy in Canada. From there, the semipalmated sandpiper (Calidris pusilla) crosses the Atlantic Ocean in a non-stop 5-day flight, whereas the semipalmated plover (Charadrius semipalmatus) flies primarily overland with stopovers for rest and feeding. Using hierarchical cluster and discriminant analysis of morphometric features to classify three-dimensionally (3D) reconstructed cells, we identified two morphotypes of radial glia, designated as Type I and Type II. The migratory process affected these cells differentially, with more intense morphological changes in Type I than in Type II morphotypes in both species. We also compared the number of doublecortin (DCX)-immunolabeled neurons with morphometric features of radial glial–like α cells in the hippocampal V region between C. pusilla and C. semipalmatus before and after autumn migration. Compared with migrating birds, the convex hull surface of radial glial–like α cells of wintering birds significantly increased in both C. semipalmatus and C. pusilla. This increase correlated with an increase of the total number of DCX-immunolabeled neurons in wintering birds. The decreased radial astrocyte morphological complexity in the semipalmated sandpiper and its increase in the semipalmated plover, a species that probably relies more on visuospatial information for navigation, may be significant, despite phylogenetic and other differences between these taxa. The migratory flight of the semipalmated plover, with stopovers for feeding and rest, versus the non-stop flight of the semipalmated sandpiper may differentially affect radial astrocyte morphology and neurogenesis.

In canine females, mammary tumors are the most frequently diagnosed, especially in nonspayed animals. They are highly aggressive, multifactorial and heterogeneous, with different histopathological, molecular and clinical characteristics, resulting in different prognoses and response to treatment. Although considered as a model for human breast cancer, little is known about these tumors in canines, and thus they are usually diagnosed at an advanced stage and with tumor resection surgery as the preferred option therapy for the species. The aims of the present study were the identification of the different canine mammary tumors subtypes, as well as potential diagnostic, prognostic and susceptibility markers. Canine samples of neoplastic and non-neoplastic mammary tissue were collected at UFRA’s Veterinary Hospital of UFRA. The identification of the molecular subtypes (Luminal-A and -B, HER-2+ and Triple Negative) was performed by the immunohistochemical technique. The identification of diagnostic and prognostic markers was performed by the quantification of gene expression of CCNA2, CCNB2, TTK, CHEK2, TP53, MDM2, PCGF1, PCGF2 and TGF1 genes by real-time PCR. Identification of susceptibility markers was performed on the Affymetrix 700k SNP array platform (Affymetrix Inc.) following the manufacturer's protocols. The correlation between the results obtained was performed by statistical analysis, and results with p<0.05 were considered significant. Immunohistochemistry analyzes showed the presence of all four molecular subtypes previously described for canines, with a higher prevalence of the subtypes that are positive for estrogen and progesterone receptors (Luminal-A and-B) and samples with Ki67 above 10%, suggesting that, although most of the samples are responsive to treatment with antiestrogens, they are mostly more aggressive, with a high rate of cellular proliferation. Except for TGF1 and PCGF2, all other genes presented diagnostic value for canine mammary cancer. Regarding the use as prognosis, the correlation between the expression of CCNA2 and Luminal-A and -B subtypes, TTK with Triple Negative, PCGF1 with survival and MDM2 with pseudopregnancy was observed. When comparing the tumor samples in relation to the control samples, several SNPs were identified in seven protein coding genes and considered as potential susceptibility markers of mammary cancer in dogs. The results of the present work have potential applicability in the veterinary routine, allowing an early identification of the tumor, as well as directing the treatment of the animal.

Patients with chronic kidney disease (CKD) on hemodialysis (HD) present oxidative stress, which is characterized by the reduction of antioxidant enzymes and increased production of free radicals, which has a strong association with cardiovascular complications. Several therapeutic strategies have been used in the sense of reducing oxidative stress in these patients, the Amazonian fruit Euterpe oleracea, known as açai, has shown that the supplementation of this fruit, produces protective effect against oxidative stress, since it is rich in phenolic compounds that are potent antioxidants. However, there are no studies that have evaluated the effect of açai on oxidative stress in chronic renal patients on hemodialysis. Therefore, the aim of this pilot study was to evaluate the effects of açai supplementation on oxidative stress markers in hemodialysis (HD) patients compared to the non-supplemented group. Eight HD patients (55.5±4.9 years) were randomized to receive 20 mL of freeze-dried and clarified açai, three times a week for eight weeks and were compared to ten HD patients without supplementation (56.1±3.4 years). Plasma levels of oxidative stress markers – malondialdehyde (MDA), nitrite, total glutathione (TG), catalase activity (CAT) and glutathione peroxidase (GPx) – were evaluated before and after supplementation. The statistical analyses were performed using the Stata 14 software, with α=5%, meaning p<0.05 considered as statistically significant. MDA plasma levels were reduced after açai supplementation from 80.2 ± 9.5 to 66.1± 14.5 pg/mL (p= 0.043). This pilot study indicates that açai intake, a very common food in North of Brazil may be an alternative nutritional strategy to reduce the oxidative stress markers in HD patients.

Despite being widely used in dentistry for dental carie control, in high amounts fluoride may be associated with side effects of which the best known is dental fluorosis. In addition, studies suggest that even at low concentrations fluoride may exerts toxicity leading to damage on CNS. Functional toxicogenomics analysis of gene profile after exposure to contaminants has been used as a tool for the identification of biomarkers of exposure, as well as for the identification of signaling pathways that may be used for treatment and / or prevention of damage caused by the toxicity of certain compounds. As the molecular mechanism of fluoride toxicity still unknow, analysis of F chronic exposure on gene expression profile of CNS cells are necessary. Here we aimed to show the effect of fluoride exposure of plasma concentration founded on population that used to be exposed to fluoridated drink water, on the main CNS cells. In this way, we have used human cell lineage IMR-32 (neurons) and U87 (glial cells) to analyze parameter of viability, morphology and cell metabolism, ATP-synthesis, oxidative stress, DNA damage and global gene expression profile after 10 days exposure. Our results have shown that fluoride does not induce changes in IMR-32 cells. On the other hand, it induces cell death by necrosis, increased metabolism, decrease in ATP and GSH / GSSG in U87 cells and DNA fragmentation. The U87 gene expression profile is differentially altered after fluoride exposure, decreasing 1735 genes and an increasing expression of 1047 genes after exposure to 0.095μg / mL and decreasing of 1863 gene expression and increasing of 1023 expression after exposure to 0.22μg / mL. We also highlighted the major molecular pathways altered after exposure, such as the signaling pathway TNF-alpha via NFK-B and mitochondrial process. We also showed genes with significant importance biology (hub genes) such as the genes PTGES3, EP300, CYP1B1, RPS27A. Our results suggests that glial cell are affected by fluorides exposure and mitochondria has a major role on the mechanism of fluoride toxicity.

The Charadriiformes represent one of the largest orders of Birds, with 19 families and around 370 species. This order is divided into 3 great monophyletic suborders: Charadrii, Scolapaci and Lari. Only three papers using molecular cytogenetics were performed in the Order Charadriiformes to date, indicating the need for many studies in this order to understand the karyotype evolution of these families. Data from the literature demonstrate that, using GGA probes, a fusion of GGA 7 and GGA 8 in Vanellus chilensis was identified, apparently a common feature in the Charadrii suborder. In this dissertation, Charadrius collaris (CCO), Vanellus chilensis (VCH) and Actitis macularius (AMA), belonging to the family Charadriidae and Scolopacidae, were analyzed by classical and molecular cytogenetics using whole chromosome probes from Burhinus oedicnemus (BOE) to detect possible chromosomal rearrangements. Zoo-FISH showed a high degree of conservation in the first seven pairs of CCO and VCH. It can be said that some pericentric inversions occurred in CCO3, CCO6 and CCO8 and many autosomes probes hybridized in the long arm of the CCO-W chromosome due to repetitive sequences. The study suggests that the fusion of two small pairs in CCO and VCH formed a metacentric pair of BOE (BOE 8), perhaps a common feature of species with a low diploid number in the suborder Charadrii and Lari, and thus a character derivative. A bird from the family Scolapacidae was also analyzed for the first time by classic and molecular cytogenetics (Zoo-FISH). The karyotype of Actitis macularius (AMA) presents high 2n (92), common to Scolapacidae and larger than the PAK karyotype, suggesting specific fission-type rearrangements for the Suborder Scolapacii, leading to medium to small macrochromosomes. The Zoo-FISH using BOE probes detected AMA fissions in all 14 pairs, as well as the remainder of microchromosomes. Inversions were observed for AMA1-4 and AMA pairs 11-14. In contrast to what was observed in the W chromosome of other species analyzed in the family, of metacentric and submetacentric morphology, in Actitis macularius this chromosome is acrocentric, suggesting that there have been inversion events for this bird.

Nesting Birds (Brown-headed cowbirds – Molothrus ater) provide us with a good
model of cognitive abilities research, since they are obligatory parasitic birds, in
which only females search for ideal nests and therefore have greater
hippocampal volume than males, as well as, higher rates of hippocampal
neurogenesis. It is also reported that captivity decreases rates of neurogenesis
and hippocampal volume. For the verification of neurogenesis rates several
studies use endogenous markers and one of them is duplacortin, a marker of
new neurons. Thus, we tested the hypothesis of how environmental conditions
(enriched and standard) and captivity time (20 days and 24 months) affect
Molothrus ater hippocampal neurogenesis. We quantified, by stereological
method, the number and volume of the sum of immunocompromised
hippocampal neurons (DCX) of 21 female Cowbirds. We also verified the
hippocampal and telencephalic volume of sections immunolabulated by NeuN
and evaluated the neuronal recruitment of the caudate-hippocampus. Our
results revealed that environmental enrichment increased the neurogenesis in
the hippocampal V and triangular region of captive birds for a short captivity (20
days) and that the rate of neuronal recruitment occurs in the caudal portion of
the hippocampus. The telencephalic volume decreased in birds that were kept
for a long period of captivity, and the hippocampal volume did not change and
the somatic volume was affected by the long captivity. Our results suggest that
captivity time influences hippocampal neurogenesis and that there is activation
of different sub-regions of the hippocampus, especially the caudalportion.
Key words: new neurons, nest parasite, V-hippocampal; stereology.

Nucleic acid testing (NAT) for virus detection during blood screening has helped to prevent transfusion-transmitted infections worldwide. In northern Brazil, NAT was implemented in 2012 for HIV and HCV and more recently, in January 2015, the screening for HBV was included and currently used concomitant with serological tests (HBsAg and anti-HBc). This study aims to evaluate the prevalence and the incidence of HBV infection among voluntary blood donors at ten regional blood centers of HEMOPA Foundation in Pará state and to compare the residual risk of transfusion-transmitted HBV infection before and after the Brazilian HBV-NAT implementation. The prevalence (restricted to FT donors) and incidence (restricted to RP donors) of HBV were calculated based on rates of confirmed positive samples. Residual risk was based on the incidence and WP model described by Schreiber and coauthors. Logistic and Poisson regression were used in the statistical analysis by SPSS v20.0. A p value <0.05 was considered statistically significant. HBV prevalence in the periods before and after the implementation of HBV-NAT were 247 and 251 per 100,000 donations, respectively. Seroconversion rates were 114 and 122 per 100,000 donations in the two periods, respectively. The residual risk (RR) for HBV decreased significantly in the period after the implementation of HBV-NAT, with a reduction of 1: 144.92 to 1: 294.11 donations (p <0.001), significantly increasing transfusion safety at HEMOP Foundation, in the Northern Region of Brazil.

Platelet concentrate (PC) is a key blood component, which even in good storage conditions, susceptible to cellular damage over time. Hence, blood banks discard unused PC bags after 5 days of storage. Biomarkers of PC quality are therefore highly sought after in blood bank governance. We used the data (Gene Expression Omnibus: GSE61856) generated with next-generation sequencing to examine the expression profiles of microRNAs (miRNAs) from PCs that were stored for 6 days in a blood bank, that is, 1 day longer than is normally stored PC. We identified the 14 most differentially expressed miRNAs by comparing a control PC on the first day of storage with the PCs on each of the subsequent 5 days of storage from day 1 to 6. In all, we identified nine miRNAs with the downregulated profile (miR-145-5p, miR-150-5p, miR-183-5p, miR-26a-5p, miR-331-3p, miR-338-5p, miR-451a, miR-501-3p, and miR-99b-5p) and five upregulated miRNAs (miR-1304-3p, miR-411-5p, miR-432-5p, miR-668-3p, and miR-939-5p). These miRNAs were validated by real-time quantitative PCR in 100 PC units. As each PC unit is composed of platelets of five individuals, the validation was thus performed in 500 individuals (250 men and 250 women, comprised 18–40 years old adults). The data were analyzed with hierarchical clustering and principal component analysis, which revealed the variation of mean relative expression and the instability of miRNAs half-life on the fourth day of PC storage, which coincides with time of onset of platelet storage lesions. These new observations can usefully inform future decision-making and governance in blood banks concerning PC quality.

Acute spinal cord injury (aSCI) is a serious pathological condition that affects several individuals in different regions of the world and may cause physical and/or psychological sequelae. The available treatment is ineffective, which demands on development of new therapeutic approaches. The development of neuroprotective agents is of fundamental importance for the tissue preservation after aSCI. In the Amazon rain forests there are a multitude of medicinal plants, whose potential anti-inflammatory and neuroprotective effects have not been investigated. Cipó-pucá (Cissus verticillata) is used for treatment of stroke in folk medicine, but its effects are not scientifically proven and have not been investigated after aSCI. In this study, we investigated the anti-inflammatory and neuroprotective effects of the supercritical extract of cipó-pucá in an experimental model of aSCI in adult rats. The extracts of leaves of cipó-pucá were obtained by extraction with supercritical fluid. The animals underwent partial hemisection surgery of the spinal cord and were treated with extract of cipó-pucá (50 mg / kg) or vehicle. They were perfused at 24 hours postinjury. The gross histopathology was performed by hematoxylin-eosin staining. Immunohistochemical analysis for visualization of neurons, microglia, astrocytes and neutrophils were performed using antibodies against NeuN, CD68, caspase-3 and MBS-1, respectively. The quantitative analysis showed neuronal preservation and, reduction of the apoptotic cells, activated microglia and inflammatory infiltrate (neutrophils) in treated animals compared to the control group, suggesting a neuroprotective and anti-inflammatory effect of the supercritical extract of cipó-pucá in the aSCI model.

To measure possible influences of masticatory changes and sedentary lifestyle on spatial learning and on the morphology of the dentate gyrus astrocytes in an aged murine model, we imposed one of three diet regimens on different experimental groups, from the 21st postnatal day onwards until 6 or 18 months of life. To that end the control group with normal masticatory activity received a pellet-type hard diet; the group with reduced masticatory activity received a pellet diet followed by a powdered diet; and the group with rehabilitated masticatory activity received pelletized diet, followed by powder and pellet again. The changing intervals were proportional and the same for each diet. To mimic the sedentary or active lifestyle, the animals were maintained until the end of behavioral tests, in either standard cages (impoverished environment) or in enriched cages (enriched environment) and then, sacrificed for perfusion with saline and aldehyde fixatives. To measure the effects of diet, environment and age on learning and spatial memory, we measured the individuals performance on the Morris water maze task and found that masticatory activity reduction, regardless of environment, decreased the average rate of spatial learning, and its rehabilitation recovered associated losses in young animals. Masticatory rehabilitation combined with enriched environment increased the learning rate in old animals. No correlation was found between the learning rate and swimming speed, suggesting that deficits and their recovery reflect cognitive performance. For the morphological studies we used selective astrocyte immunolabeling directed to glial acid fibrillar protein (GFAP), reconstructing microscopically in three dimensions, those located in the outer one-third of the molecular layer of the dentate gyrus. 1800 cells were digitally reconstructed and the morphological study using hierarchical cluster analysis revealed two morphological phenotypes, designated type I and II that were differentially affected by the studied variables. Aging reduced the complexity morphology of astrocytic trees while masticatory change reduced only in young animals, increasing the complexity of the branches in old animals. In opposition to that, enriched environment seems to minimize these morphological changes. We conclude that reduction of masticatory activity and aging in mice impairs spatial learning in Morris water maze, with a reduction in complexity of astrocytic branches. The rehabilitation of masticatory activity seems to recover these losses and a combination of enriched environment and rehabilitation offers significant benefits for both young and old mice. Although not linearly, morphological complexities increased as a function of spatial learning and memory performances.

Obesity is defined as an abnormal or excessive accumulation of fat that can be harmful to health and has been considered epidemic, since it is a disease with high prevalence in most countries of the world. Currently there is the idea that deficiencies in cognitive functions associated with the frontal lobe, contribute to the maintenance of obesity, however, there are investigations that contradict this postulate. On the other hand, the patterns of visual perception, measured with the Rorschach test, have been linked to weight gain and obesity, the results that determined this relationship are not conclusive. The main objective of this study was to determine if obesity or bariatric surgery generate differences in the patterns of visual perception and humans cognitive functioning. Additionally, we sought to relate the neuropsychological functions of the cortex occito-temporo-parietal, which participate in the perception of visual stimuli, with the neuropsychological functions of the prefrontal cortex. The research included the participation of 48 subjects, divided into 3 groups (diagnosed with obesity, undergoing bariatric surgery and a control group), which were evaluated with the Rorscahch test and the Stroop and MCSTneuropsychological tests. Our results showed similar values for the three groups in the measurements made with the neuropsychological tests and with the visual perception test. In addition, three indicators of the visual perception test were correlated with indicators of sustained attention, inhibitory control and cognitive flexibility. Our main conclusion is that the obese or bariatric subjects do not present differences in cognitive functioning or visual perception patterns. We also conclude that there are indicators of the Rorschach test that present a potential to be considered neuropsychological indicators.

The heavy and episodic EtOH drinking pattern, equivalent to weekend consumption, characterize the binge-drinking pattern and promotes a misbalance of encephalic metabolic functions, concurring to neurodegeneration and cerebral dysfunction. And for being a legal drug, it has a global public health and social relevance. In this way, we aimed to investigate the effects of physical training, in treadmill over the EtOH deleterious effects on hippocampal functions, related to memory and learning. For this, we used 80 Wistar rats, divided into four groups: Control, Trained group (trained animals with doses of distilled water); EtOH group (non-trained animals with doses of 3g/kg/day of EtOH, 20% w/v); and EtOH+Trained group (trained animals exposed to EtOH). The physical exercise was performed on running treadmill for 5 days a week for 4 weeks and all doses of EtOH were administered through intragastric gavage in four repeated cycles of EtOH in binge. After the experimental period, the animals were submitted to object recognition task and Morris’ water maze test, and after euthanized, the blood and hippocampus were collected to Trolox Equivalent Antioxidant Capacity (TEAC), Reduced Glutathione Content (GSH), Nitrite and Lipid Peroxidation (LPO) levels measurement. Our results showed that EtOH caused marked oxidative stress and mnemonic damage, and the physical exercise promoted neuroprotective effects, among them, the modulation of oxidative biochemistry in plasm (by restoring GSH levels) and in hippocampus (by reducing LPO levels and increasing antioxidant parameters) and cognitive function improvement. Therefore, physical exercise can be an important prophylactic and therapeutic tool in order to ameliorate and even prevent the deleterious effects of EtOH on cognitive functions.

The inflammatory response may exacerbate the damaging process after acute neural disorders such as in stroke. Alternatives to obtain a decrease in the inflammatory response in the encephalic cell accident have been widely studied with the use of herbal compounds, in this hypothesis the pucá cucó (Cissus verticillata), an Amazonian medicinal plant popularly used as anti-inflammatory and antihyperglycemic used by folk medicine in the treatment of acute inflammatory diseases. However, there are no investigations into the possible anti-inflammatory and neuroprotective effects of plant extract in experimental models of acute neural disorders. In this study, we investigated the anti-inflammatory and neuroprotective effects of plant extract by supercritical extraction in adult rats submitted to acute injury induced by endothelin-1 (ET-1) in the motor cortex. Two experimental groups were delineated: the first with animals of the control group with a survival time of twenty-four hours and seven days (Group N = 3 for each survival time), submitted to focal ischemia with ET-1, but injected 5% tween intraperitoneal (ip), and the second group of animals treated with doses of 100 mg / kg (ip) of plant extract after surgery with the same survival times (Group N = 5 for each survival time). Then perfused twenty four hours and seven days after induction of ischemic injury. General histopathological analysis was performed in sections stained by cresyl violet and hematoxylin. Neutrophils and macrophages were identified by immunohistochemistry with specific antibodies (anti-MBS1 and IBA-1, respectively), astrocytes labeled with anti-GFAP antibody. Activated microglia/ macrophages and neuronal bodies were counted in the mentioned experimental groups and the astrocyte activity after the lesion was evaluated. Treatment with Cissus verticillata extract induced anti-inflammatory and neuroprotective effects in treated animals, as well as decreased tissue cavitation, astrocyte activation at the center of the lesion and decreased infiltration of polymorphonuclear and/or microglia/ macrophage inflammatory cells.

Lead (PB) is a heavy metal, which can be utilized in the production of several compounds. The main route of human exposure is through the consumption of contaminated food or water, and once absorbed, about 99% of the circulating lead spreads to soft tissues, teeth, bones and brain. In the Central nervous system (CNS), several studies have demonstrated deficits in learning capacity, cognition and intellectual development in humans exposed to lead during a given period of life. However, it is poorly understood the mechanisms of action involved with the toxicity of Pb. From this, this study aimed to evaluate the exploratory, motor and tissue effects induced by the subchronic exposure of young wistar rats to 50 mg/Kg of lead, associated with possible mechanisms of action. Male Wistar rats were exposed for 55 days at a dose of 50mg/Kg of Pb per gavage, and the control animals received distilled water. The open field, inclined plane and route-rod tests were performed for locomotor evaluation. Staining was performed with Hematoxylin and Eosin, as well as immunohistochemistry for the quantification of mature neurons, myelin sheath and synaptic vesicles. To evaluate the protein expression, the Proteomic profile was performed. The statistical analysis was performed by Student's T-Test, being considered significant p < 0.05. After we observed lead deposition only in the cerebellum, it was possible to characterize exploratory and motor deficits in the rats exposed to lead, and we observed a decrease in the number of Purkinje cells, as well as mature neurons, reduction of vesicles synaptic and decreased myelin sheath. In the evaluation of oxidative stress induction, it was possible to evaluate the increase of MDA and nitrite only in the motor cortex. And in the evaluation of protein expression, both regions presented alterations in proteins responsible for the release process of neurotransmitters, as well as receptors and second messengers, and also proteins involved in the process of apoptose. Thus, we conclude that the subchronic exposure to low Pb dose of young Wistar rats promoted locomotor and histological tracings, associated with induction of oxidative stress, alterations in the process of cell signaling, as well as death by apoptosis.

Dapsone (DDS), a drug used in leprosy multidrug therapy, can cause many adverse reactions and intoxications, inducing the generation of reactive oxygen species (ROS) and imbalance in the redox state, increase methemoglobin (MetHb) formation, hemolysis and release of heme and iron free, which may interfere with redox homeostasis in more vulnerable regions, such as prefrontal cortex (PFC), causing neurotoxicity and even neuroinflammation. In this sense, antioxidant compounds with chelating properties such as α-lipoic acid (ALA) may play a key role in combating or preventing these alterations. Thus, this work aims to evaluate the effect of DDS on MetHb formation, hematological changes and peripheral oxidative stress, as well as oxidative changes and neuroinflammation in PFC. For this, was induced MetHb formation in Swiss mice with DDS 40mg/kg ip for 5 days. Two hours after DDS administration, ALA was given at two concentrations (12.5 and 25 mg/kg). Besides MetHb percentage, total equivalent antioxidant capacity (TEAC), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) thiobarbituric acid reactive substances (TBARS), and iron concentrations in blood and PFC were evaluated, as well as, IL-1β, IL-17, and IL-4 cytokine concentrations, and de F4/80+, GFAP, and BDNF expression in PFC. Our results show that DDS induces the MetHb formation in red blood cells of mice, however, ALA was able to prevent or reverse the oxidation of hemoglobin induced by DDS at two used concentrationns. DDS reduced antioxidant capacity (TEAC) in plasma and red blood cells; decreased erythrocyte GSH, CAT, and SOD; and increased TBARS and plasma iron; however, ALA at two concentrations increased or reestablished TEAC in plasma and red blood cells at baseline levels. In addition to increasing or reestablishing GSH levels, SOD, and CAT in red blood cells, and decreased TBARS and iron levels, mainly in euthanized animals 4h after treatment. Curiously ALA 50mg/kg increased plasma iron concentrations. The treatment with DDS 40mg/kg also reduced TEAC, GSH, SOD e CAT in the PFC of the mice and increased TBARS and iron, characterizing oxidative stress, mainly in euthanized animals in 24h after treatment. Treatment with ALA increased or restored TEAC and GSH; and increased SOD and CAT in 12,5mg/kg concentration in euthanized animals 4h after treatment, as well as reducing TBARS levels and decreasing or preventing iron overload, mainly in euthanized animals 24h after treatment. DDS also promoting microglial and astrocyte activation in PFC, through F4/80+ e GFAP expression., with increased IL-1β and IL-4 production, and BDNF reduction, on the other hand, ALA 25mg/kg reduced GFAP and IL-1β expression, besides increased BDNF, suggesting that DDS also can cause neuroinflammation, and ALA can antioxidante and anti-inflammatory properties against toxicity caused by DDS. This results suggest that ALA is promising and plays an important role in the prevention and/or formation of MetHb, reestablishment of redox balance and iron concentrations in both blood and PFC. Thus, ALA may be a usefull adjuvant therapy in DDS-induced toxicity, with lower toxicity and facilitating adherence to treatment of leprosy patients.

Fluconazole is a broad-spectrum triazole antifungal that is well-established as the first-line
treatment for Candida albicans infections. Despite its extensive use, reports on its
genotoxic/mutagenic effects are controversial; therefore, further studies are needed to better
clarify such effects. African green monkey kidney (Vero) cell line were exposed in vitro to
different concentrations of Fluconazole and were then evaluated for different parameters, such
as cytotoxicity (MTT/cell death by fluorescent dyes), genotoxicity/mutagenicity (comet
assay/micronucleus test), and induction of oxidative stress (DCFH-DA assay). Fluconazole was
used at concentrations of 81.6, 163.2, 326.5, 653, 1306, and 2612.1μM for the MTT assay and
81.6, 326.5, and 1306μM for the remaining assays. MTT results showed that cell viability
reduced upon exposure to Fluconazole concentration of 1306μM (85.93%), being statistically
significant (P<0.05) at Fluconazole concentration of 2612.1μM (35.25%), as compared with
the control (100%). Fluconazole also induced necrosis (P<0.05) in Vero cell line when cells
were exposed to all concentrations (81.6, 326.5, and 1306μM) for both tested harvest times (24
and 48 h) as compared with the negative control. Regarding genotoxicity/mutagenicity, results
showed Fluconazole to increase significantly (P<0.05) DNA damage index, as assessed by
comet assay, at 1306μM versus the negative control (DI=1.17 vs DI=0.28, respectively).
Micronucleus frequency also increased until reaching statistical significance (P<0.05) at
1306μM Fluconazole (with 42MN/1000 binucleated cells) as compared to the negative control
(13MN/1000 binucleated cells). Finally, significant formation of reactive oxygen species
(P<0.05) was observed at 1306μM Fluconazole vs the negative control (OD=40.9 vs OD=32.3,
respectively). Our experiments showed that Fluconazole is cytotoxic and genotoxic in the
assessed conditions. It is likely that such effects may be due to the oxidative properties of
Fluconazole and/or the presence of FMO (flavin-containing monooxygenase) in Vero cells.

Central Nervous System Tumors (CNS) account for approximately 2% of all cancers. Although the incidence of CNS tumors is small, compared to other neoplasms, these tumors are among the most serious human malignancies because they affect the organ responsible for the coordination and integration of all organic activities. Gliomas represent approximately 80% of all intracranial tumors, typically affecting adults, with a high incidence between 40 and 65 years of age. Although numerous anti-glioma drugs have already been developed, they induce adverse reactions and their therapeutic effects are not satisfactory. The objective of this study was to evaluate and compare the profile of Copy Number Variation (CNV) and gene expression of patients diagnosed with gliomas and in glioblastomas cell lines (U87-MG, U343, AHOL1 and 1321N1) treated with pisoterol. For rhe experiments done with the cell lines treated with pisoterol, we demonstrated that they were highly sensitive to pisoterol treatment. This drug reduced the number of live cells in a dose-dependent manner. In addition, we demonstrated that after 48h of exposure to pisoterol, all cell lines were blocked in G2/M. Finally, we demonstrate that the pisosterol can modulate the expression of several genes of ATM/ATR pathway, promoting apoptosis. We demonstrated on genomic scale that all the cell lines had more genes that were significantly down-regulated than up-regulated after the treatment with pisosterol. For the experiments done with the gliomas biopsies, we demonstrated that only 11 genes (TNFRSF1A, SNAPC2, CASP8, IRAK3, GPX3, FZD9, TFAP2C, CDH1, RPRM, POU4F3 and MGMT) exhibited changes in the pattern of methylation in all grades analyzed. In addition, the methylation pattern of these 11 genes had correlations with some clinicopathological characteristics, such as age, sex and histological grade. And finally, we made a molecular characterization describing the CNVs of the gliomas originating from Belém-PA.

This study investigated the growth of the tambaqui (Colossoma macropomum) (Cm), an caracid teleost in the Amazon region, in the laboratory. Juvenile fish were submitted to the simulation of the natural conditions of feeding, climate and running water, corresponding to the flood and dry periods of the Amazonian hydrological cycle. In the flood, its diet is predominant of fruits and seeds, the environment is mild (28 ± 2°C) and the current is higher (0.2 to 0.3 m/s). In drought, the feed is based on animal protein, there is no current and the average temperature rises (34 ± 2°C). Therefore, the aim of this study was to investigate the effects of Myrciaria dubia (Md) on the growth of Cm in the drought or flood simulations with respect to the mild (28 ° C) or heated (34 ° C), standing or running water (0,2 or 0.3m/s), and diet with higher (45%) or lower (32%) crude protein (CP) content. For this, juveniles of Cm were acclimatized (70 or 126 days) in tanks of (310 or 500 liters)
according to the experimental protocol. Protocol I: diet with fractioned daily supply (3x/day) and supplemented with Md; crude protein (45 or 32%); running water (0.2 m/s) or stopped at 28 or 34°C; analysis of muscle contents of IGF1 and total lipids. protocol II: single or fractioned offer (3x / day); standing or running water (0.3 m/s), intercalated, (12 hours) or continuous; quantification of the cavity fat mass. The results are presented on average plus or minus the standard error of the mean and compared by ANOVA plus Bonferrone post-test. Correlation test for weight, length or cavity fat versus running water; in the conditions of single or fractional supply was performed to verify interrelations between the phenomena studied. A potentiation of body mass expansion rather than length occurred by the diet supplemented with Md in standing and heated water. In contrast similar potentiation occurred for running and heated water in the 45% CP diet. In turn, lower growth performance (weight and length) was observed in the group submitted to a 32% CP diet. The running water also
potentiated the accumulation of cavitary and muscular fat of total lipids, suggesting that the swimming effort demands accumulation of potential energy possibly related to the preservation of protein anabolism, since the protein content in the muscle tissue was not altered. On the other hand, the single daily supply of food was not enough to maintain the resulting growth performance to sustained swimming (running water). In the fractioned supply, the group submitted to continuous running water showed the best performance, suggesting that sustained swimming in running water may be a determinant factor for the growth of Cm if it is offered a diet with high protein content, considering the warm environment as the most favorable. Finally, the increased IGF-1 content in the muscle confirms the participation of this growth factor as the final pathway of humoral regulation of muscle hypertrophy. Hypertrophy results in increased swimming effort, and, surprisingly, in response to diet supplemented by Md.

Chromoblastomycosis (CBM) is a fungal disease characterized by chronic cutaneous and subcutaneous lesions, due to the previous transcutaneous implantation of different black fungi, belonging to the family Herpotrichiellaceae, the main agent belonging to the genus Fonsecaea. The Amazon region is the main endemic area of Brazil and our state is the main endemic area in the country and second in the world. There is no standardization of treatment, drug therapy is used, with different regimens, mainly itraconazole. New azolics such as posaconazole and voriconazole began to be used, but with limitations due to the high cost, the use of physical methods such as cryosurgery, thermotherapy, laser therapy and both. The low cure rates and high rates of relapse of the disease may be related to the different treatment methods employed and the lack of a standardized regimen itself. The objective of this work was to evaluate the in vitro sensitivity of conidia and in vitro induced muriform cells of Fonsecaea spp. in the presence of different antifungal agents, to date there are no studies evaluating the action of drugs using the pathogenic form of the fungus, reinforcing the importance of this study, following the method established in the standard M38-A2, Clinical and Laboratory Standards Institute. The minimum inhibitory concentration for each drug was obtained after 5 days of interaction, posaconazole showed better in vitro inhibitory activity for conidia (CIMMG = 0.632μg / ml) and muriform cells (CIMMG = 1μg / ml). In the analysis of the fungicidal concentration, in both conidia and muriform cells, posaconazole presented lower value (CFMMG = 6.72μg / ml, in both). The fungus samples presented distinct times to differentiate their conidia in muriform cells, therefore we believe that although they belong to the same genus the fungi present physiological peculiarities still unknown. In the in vitro susceptibility tests PCZ had the lowest inhibitory and fungicidal concentrations in both conidia and muriform cells, thus investing in susceptibility testing was important to identify sensitive or resistant strains.

In endemic areas of Asia, Oceania, Central and South America and in the horn of Africa P. vivax malaria is a major cause of morbidity with 35 million cases annually. In Brazil, the Amazon region concentrates almost all cases and infections registered countrywide, with more than three hundred thousand cases per year. Several evidences suggest that an exacerbated inflammatory response associated to density parasite is likely to aggravate the malaria symptoms. We assessed the haematological and immunological aspects, genetic alterations related to CNVs that could lead to phenotypic alterations, conferring resistance or susceptibility to malaria, as well the presence of polymorphisms in cytokine genes and their association with the infection in patients living in a gold-mining area in a gold-mining in the Brazilian Amazon Region, establishing patterns of immune response characteristic of primary malaria, recurrent malaria and endemic control. Six SNPs (TNFA-308G/A, IFNG+874T/A, IL6-174G/C, IL10-1082G/A, -819C/T, -592C/A) in four genes were determined; blood cell count was conducted on automatic analyzer; plasmatic cytokines IL-6, IL-10, TNF-α and IFN-γ were quantified by flow cytometry and density parasite was estimated by thick blood films with confirmation by nested-PCR; the CNV was estimated by aCGH and association between copy number and phenotypes (parasite load, mean number of clinical infections of malaria and gender) was assessed. The statistical analyzes were performed by Graph-pad prism 6.0 and Bioestat 5.0. No significant association was found between SNPs and malaria infection; cytokine levels were higher in malaria group when compared to endemic control; production of IL-10 was higher in the presence of GCC/GCC haplotype; IFN-γ levels were correlated with previous malaria episodes; malaria patients showed lower platelet numbers, reduction on white blood cells count and an increased monocyte percentage; significant increase in the IL-6 and IL-10 plasmatic levels in both malaria groups; the primary malaria patients displayed the highest significant plasmatic IFN-γ levels; recurrent malaria patients displayed the highest significant plasmatic TNF-α; malaria infection demonstrated correlation between parasite density and TNF-α, IL-6 and IL-10 levels; a total of 112 amplified genes and 12 deleted genes were observed and the CNVs found did not include any gene related to receptors or vivax malaria resistance factors. There were no
xx
statistically significant correlations between the clinical and pathological data (parasite load, mean number of clinical infections of malaria and gender) and the presence of CNVs in the patients studied. This study provides additional data on Plasmodium-host immune response and describes the quantitative changes in the human genome in P. vivax infection in an endemic area of garimpo.

Anxiety-like behavior can be defined as a state of apprehension where the danger is imminent and may occur from exposure to new environments or uncontrollable aversive stimuli. Many neurotransmission systems may be involved in the modulation of anxiety states in mammals as well as in teleosts. Among these, the GABAergic and glutamatergic systems are the main modulation pathways of anxiety-like behavior. Therefore, the present work aims to evaluate the extracellular levels of GABA and glutamate throughout the process of anxiety generation in Danio rerio exposed in Dark/light Preference (DLP) and Novel Tank (NT) tests. Sixty animals (Danio rerio, (wild type, longfinn) were used, which were exposed to DLP and NT at times 5, 10 and 15 minutes. The parameters analyzed for DLP were: time in the white compartment, number of quadrants crossed in the white compartment and transitions between compartments; for the NT, the parameters were: Time in the upper half, number of squares crossed, entrances at the top, maximum speed, average speed and total distance traveled. Then, the brains were dissected and incubated with Hank/Na+ for further quantification of GABA and Glutamate by High Performance Liquid Chromatography (HPLC). All tests were filmed and videos evaluated using Zebtrack software. One-way ANOVA test with Tukey post-test was applied, considering significant values p<0.05. Data were expressed as mean ± standard error mean and all experiments were previously approved by the local ethics committee (CEPAE UFPA 213-14). Our results demonstrate exploration of the white compartment in the LDT test, with no difference between the times (F [3, 20] = 17.10) and no change in the number of midleline crossings between the compartments between minutes 5 and 10 (F [3,20] = 6.28, p <0.05). There was an increase in the number of squares crossed in the time of 15 minutes in relation to the other exploration times (F [3, 20] = 13.04, p <0.03).In addition, there was an increase in extracellular glutamate content during the test (F [4, 10] = 8.98) and decrease of GABA in the last minutes compared to animals not exposed to the test (F [4,9] = 20,83; <0.05). The behavioral patterns of the animals exposed to the NT test also vary according to the time of exposure, where, as time increases, there is an increase in the time of the top exploration (F [3, 28] = 15.99, p <0.01), (F [3, 22] = 16.86 p <0.05), increase in the number of squares crossed (F [3, 21] = 38.70, p <0.01), increase in the total distance traveled [3, 27] = 61.44, p <0.01), with no change in maximum speed (F [3, 28] = 19.73, p <0.01) and mean speed at all times. Glutamate levels increase on exposure to the test (F [4, 10] = 24.62) and GABA levels remain unchanged (F [4,9] = 1.76). We conclude, therefore, that glutamatergic and gabaergic systems modulate the anxiety-like behavior in Danio rerio differently.

Methylmercury (MeHg) represents the most toxic form of mercury, which in chronic intoxications induces motor and cognitive impairment in adult rats. Studies suggest that this metal has a tropistic effect on the cerebellum, however few researches aim to elucidate the mechanisms associated with low-dose MeHg-induced damage in a subchronic exposure model. Thus, the objective of this study was to verify motor, tissue, oxidative and proteomic biochemical alterations induced by subchronic exposure to low doses of MeHg. Fifty six male Wistar rats, 90 days old, were divided into two groups: control group (distilled water) and exposed group (0.04 mg / kg / day of MeHg), both administered via intragastric gavage for 60 days. After the exposure period, the open field and rotarod behavioral tests were performed. Subsequently, the cerebellum from these animals were collected for biochemical analysis, proteomics, mercury tissue deposits, and immunohistochemistry evaluation. Statistical analysis was performed using the Student's t-test, considering a significant value of p <0.05. The proteomic profile was analyzed by the ProteinLynx Global SERVER ™ software (PLGS). Proteins with p <0.05 were considered super-regulated proteins and those with p <0.95 were considered as sub-regulated proteins. The test used was Fisher's exact test with Bonferroni correction. Our results demonstrated a decrease in the motor tests of the animals exposed to MeHg. Open field test showed a decrease in total distance covered and the number of rearing in comparison to the control group with p <0.05. Rotarod test presented a decrease in the time for the first latency to fall and an increase in the number of falls in the MeHg group in comparison to the control with p <0.05. The biochemical evaluation showed an increase in nitrite and lipid peroxidation levels and a reductions of Antioxidant Capacity Against Peroxils radicals (ACAP) with p <0.05. Considering the proteomic profile of these animals, among the 1220 proteins identified, 436 proteins were found exclusively in the control group and 311 proteins exclusively in the MeHg group. Also, 358 proteins were found overexpressed and 115 subexpressed proteins. All proteins interactions were depicted on 3 interactions networks to perform proteomic alterations analysis. In addition, the tissue evaluation showed a decrease in Purkinje cells and NeuN + cells and a smaller amount of IBA1+ cells. Area fraction analysis showed a smaller number of GFAP positive cells, synaptophysins and MBP +. Thus, our results suggest that MeHg intoxication provoked cellular and proteomic damage probably related to induced oxidative stress and also reflecting on motor deficit in behavioral tests.

Hypotonia is considered a movement disorder and as a consequence it has reduced
motor activity, a pathological condition which muscle tone is extremely reduced causing
limb weakness and flaccidity, associated with decreased muscles resistance and
passive stretching. Hypotonia is most commonly seen in the trunk and neck
musculature, causing a lack of head support. The exact incidence of hypotonia is
difficult to determine because it haven’t a specific diagnosis. However, the causes of
this disorder have many origins and may be derived neurodegenerative, neuromuscular,
lesions, chromosomal and metabolic disorders, those that affect the central nervous
system have greater prevalence, besides being involved in more than 500 different
genetic deseases, among others of unknown origin. Thus, biomechanics of the neck
and head including its components (cervical spine, muscles and nerves) are directly
affected by the pathological posture of the affected individuals, as well breathing,
feeding and interaction with the environment in which they are inserted. Currently there
are assistive technologies that benefit hypotonic, but are simple cervical supports that
do not offer any type of mobility for the user. For this purpose, the present project
proposes the construction of a head and neck support apparatus with low relative cost
that promotes some mobility to the individual, either in a passive (control-dependent)
way, through an application developed by the research group that will be controlled
remotely through Bluetooth®-type communication, It will also require supervision of the
therapist, allowing training in many environments, facilitating postural control in different
magnitudes, promoting the improvement of the quality of life of the user.

Cerebral malaria (CM) is one of the most severe complications attributed to protozoal infection by Plasmodium falciparum, gaining prominence in infant mortality rates in endemic areas. It´s a complex pathogenesis and still little elucidated, being associated with cognitive, behavioral and motor changes. Aiming to broaden the knowledge about this pathology and looking for the benefits attributed to the daily consumption of antioxidants, the objective of this work is to evaluate the possible protective effect of Euterpe oleracea fruit (açaí) during evolution of experimental cerebral malaria (ECM) induced in murine model by means of inoculation of Plasmodium berghei (PbA), ANKA stain. For this, we used the Swiss line, which were inoculated intraperitoneally (i.p.) with 10⁶ of parasited erythrocytes. The animals (females and males between 4 and 6 weeks) were divided into four groups, among which Açaí and PbA+Açaí groups were maintained on a ration-exclusive diet enriched with açaí and the Control and PbA groups were given only standard ration during 22 days of experiment. To characterize the ECM framework, several parameters were evaluated such as the appearence of clinical signs, survival curve, parasitemia, body mass gain and vascular permeability. The SHIRPA protocol was used to evaluate the behavioral and locomotor changes in animals. We observed an extension of survival of the infected animals and treated with a diet enriched with acai berry, and decreased the neurological changes arising from the exposure of the cerebral parenchyma. This work allowed us to validate the development of the experimental brain malaria framework in murine model and evaluate the neuroprotective effect of Acai (Euterpe oleracea) in the course of the disease.

Introduction: The increase in urban violence has led society to charge the State with more severe and punitive measures to solve the problem of juvenile crime. One of the proposals is the reduction of the criminal majority from 18 to 16 years. Discussions on this proposal have been ideologically polarized and instances where the debate is based on reliable scientific evidence are rare. In this research, we try to contribute to identify the implicit social and moral constraints associated with the issue of criminal majority. For this, we designed two experiments to evaluate how socioeconomic factors, sociodemographic factors and the moral development of the individual influence the opinion on the topic. Objective: To verify the relationship between socioeconomic factors, sociodemographic factors and moral development in the opinion about the reduction of the penal majority. Materials and Methods: This is a qualitative and quantitative research with a cross-sectional design that consisted of two experiments: Belem Experiment and Regional Experiment. In the Belém Experiment the data were collected in two public places of the municipality of Belém, Pará, Praça Batista Campos and the Court of Justice of the State of Pará. In the Regional Experiment an on line tool was used with the aim of achieving people from different regions of the Brazilian territory. The sample consisted of individuals older than 18 years of both sex. The instruments used were: (1) Socioeconomic and sociodemographic questionnaire and (2) Dilemma of the adolescent in conflict with the law. Pearson's Chi-square test (χ2) and data mining were used for data analysis. Results: Juvenile court workers display preference for lower stages (stage 1) and a lower level of moral competence (average c-index) (3.97), with a strong adherence to the law, different from the general public that prefers higher stages (stage 6) and c-index (14.29). There was a significant relationship between the stage preference and the opinion of the subjects, only in the juvenile court workers (χ2 = 20,665, df = 10, p = 0.024). However, the former is less in accordance with lowering the age of criminal responsibility than the latter. Conclusion: The accuracy of opinion is greater at the extremes of psychological distance, that is, when the individual is very distant or very close to the reality of this adolescent.

The color vision and the luminance vision are of great importance in the diverse activities of the human being and therefore deficiencies in these visual functions can greatly compromise the work power and life quality of a person. Several visual assessment proposals have been developed in computerized and non-computerized platforms. The tools for evaluating color and luminance vision, using variegated mosaic type stimuli, currently present on the market, have little or no user control over stimulus parameters. This dissertation aims to present the development of a program that allows the user to control most of the parameters of the mosaic stimuli. For the development of this program was used the unified modeling language (UML) that allows the specification, documentation and visualization of program objects through standardized diagrams. The program was written in MATLAB language and an executable was created to use the program by the user. The final program was called MOSAIC and allows the creation of a wide variety of variegated mosaic stimuli. The program has a greater number of advantages than other proposals of generators of this type of stimulus and could contribute with the visual scientists interested in the study of color and luminance discrimination.

Bronchopulmonary carcinoma is the most frequent in the world, being one of the most aggressive neoplasms, with a mortality / incidence ratio of around 90%, with overall survival in five years low, about 10 to 15%, in most populations of the world. In the Northern Region of Brazil, this pathology is the third most frequent among men and the fourth among women. From the anatomopathological point of view, lung cancer is classified into two main types: small cells and non-small cells, the latter being the most incident, accounting for 75% of cases. Currently, the distinction between subtypes is based on histological, immunohistochemical, and molecular differences. In this context, it is important to emphasize that molecular information influences not only diagnosis, prognosis, but also therapeutic behavior. Several genetic and epigenetic alterations of the nuclear genome are related to the pathogenesis of this tumor. However, changes in oxidative phosphorylation resulting from mitochondrial dysfunction have long been suggested as involved in the process of tumorigenesis. Thus, the present study analyzed two mitochondrial DNA (ND1 and ND3) genes belonging to the I complex of the mitochondrial respiratory chain in 66 lung tissue samples from patients with and without non-small cell lung cancer in the population of the state of Pará. the sequencing analysis identified four alterations in the ND1 gene: C3553T, T3552A, C3595ins and G3666A and only two changes in the ND3 gene: A10398G and C10400T. Among the alterations found in the ND1 gene, no statistical significance was observed in relation to the development of lung cancer. However, a structural alteration in the ND1 gene was found in the presence of C3595ins, not yet described in the literature. Whereas, the presence of the A allele, observed in T3552A in the ND1 gene, was significantly associated with a protective effect on the development of lung cancer. Already changes in the ND3 gene (G10398A and T10400C) were significantly associated with lung cancer, these changes in ND3 being potential for use as markers in patients with non-small cell lung cancer
Keywords: Non-small cell lung cancer, mitochondrial DNA, ND1, ND3, Diagnostic value and prognostic markers.

Cervical cancer (CC), which is of great importance for public health, is considered to be the 4th most common type of cancer in the world. Human papillomavirus (HPV) infections are the main risk factor. Approximately 70% of women with CC are in less developed regions, demonstrating a socioeconomic relationship. Papillomavirus belong to the family Papillomaviridae, with more than 40 genera, of which five are composed of HPVs, with at least 200 species already described associated with human infections. These virus are enveloped, spherical and have a double-stranded DNA genome. HPVs have tropism by epithelial cells and persistent infections can lead to progressive intraepithelial transformations with evolution to precursor lesions of cervical cancer, and finally cancer. HPV infection is the most common sexually transmitted infection in the world, and most sexually active people, men and women, will have contact with the virus at some point in their lives. In the present study, the cytopathological profile of patients treated at a Secondary Reference Unit in Gynecological Cancer of the city of Belém / PA and the activity of caurenoic acid against cervical cancer lines were analyzed. The profile of the microbiological and cytopathological findings was verified in the examinations carried out by the Casa da Mulher laboratory during a period of one year, using data from 2,202 cervical cancer preventive exams (PCCU), showing a weak correlation between age range and frequency of microbiological findings and pathological alterations. The microbiological findings were the presence of three species: Gardnerella vaginalis (23.48%), Candida sp. (12.44%) and Trichomonas vaginalis (0.68%). The prevalence of cytologic abnormalities corresponded to 5.72%. Atypia cells of undetermined significance corresponded to 2.679%, and the total proportion of potentially malignant neoplastic lesions was 1.09%. The increase in PCCU coverage in the female population needs to be achieved and health promotion must be effected through intersectoral partnerships, popular participation, and collective accountability for quality of life. On the other hand, the evaluation of the genotoxic and mutagenic effect of caurenoic acid (CA) in cervical cancer lines was performed using HeLa (HPV18-positive), CaSki (HPV16-positive) and C33A (HPV-negative). AC showed a strong positive correlation with the genotoxicity indicators evaluated. At high concentrations, it inhibited the expression of E6 and E7 HPV genes, which interfere with cell cycle regulation. Although genotoxic effects were observed, the assays pointed to the possibility of using CA as feedstock for therapeutic agents against cervical cancer with HPV, as well as future research on E6 and E7 functions.

The most common cancer of the thyroid is the papillary carcinoma (PTC), which represents 80% of the cases of cancer affecting this gland. PTC is a malignant tumor, with slow evolution, found in any age, but with a higher occurrence in patients between 30-40 years old. The metabolic pathway MAPK is the most associated with PTC. Among the several proteins which have a role in this pathway, we highlight the ones encoded by the genes belonging to families RAS and BRAF. Considering that there are few clinical and genetic studies focusing on thyroid cancer from Brazilian Amazonian region, the aim of this study was to investigate the occurrence of alterations in genes HRAS, NRAS, KRAS and BRAF in patients with PTC treated in a public hospitals, from Belém (PA), seeking to make an association between the mutations found and the biochemical and clinical findings. To achieve this goal, polymerase chain reaction (PCR) and direct automatic sequencing were used. Statistical analyses were performed using the software SPSS version 21.0. Continuous data were expressed as means and standard deviation and categorical data were described in terms of percentages. Student t Test was used to evaluate the continuous variables, while Fisher exact test and Chi-square were used to analyze categorical variables. We considered p<0.05 as significant value in all the analyses. Our results showed that, among the analyzed genes, only BRAF showed a mutation, BRAFV600E, in 21 out of the 53 patients (16 female and 5 males, 39.6%). Additionally, a new mutation in codon 38 of gene K-RAS was found (p.D38E). Considering clinical data, we found a significant association between the BRAFV600E mutation and hoarseness, as well as between this mutation and lymph node metastasis. In addition, the observation of a new mutation in the K-RAS gene indicates that the number of gene changes involving the MAPK pathway is still incomplete. The data obtained can be used for a better pre-surgical evaluation of thyroid tumors, in order to increase the sensitivity for the detection of cancer and avoid unnecessary surgeries of lesions erroneously identified as malignant.

5-Hydroxy-2-hydroxymethyl-γ-pyrone (AK), a known inhibitor of tyrosinase, an enzyme important for melanin synthesis and therefore used for pigmentation disorders. AK also promotes significant activation of macrophages and promotes cytoplasmic accumulation of reactive oxygen species (ROS), suggesting its role as a potentiator of the immune system and microbicide. There is no work in literature that shows the action of AK in the central nervous system (CNS) as a cellular activator and its possible protective role against infections. To test this hypothesis, it use retinal Muller glia which have similar properties to those of macrophages. Therefore, the present work evaluates the action of AK as a possible protective role in LPS-induced cell death in culture of glial cells from chicken embryos. Cultures enriched with glial cells were treated with AK (10, 25, 50 and 100 μM) and LPS (0.1, 10, 100, and 500 ng / ml) for 24 hours. After treatment, the cells did not show AK-treated cytotoxicity; however, treated with LPS, cell death occurred in a dose-dependent manner. We verified the accumulation of EROs in groups treated with AK (100 μM) and LPS (100 and 500 ng / ml). Cultures co-treated with AK and LPS in the same concentrations there was a reduction of accumulation of EROs. AK was also able to inhibit the activity of antioxidant enzymes, (catalase and Superoxide dismutase) and glutathione levels, while LPS produces an increase in the activity of these antixodants. AK was able to inhibit the antioxidant enzymes and glutathione from the increase induced by LPS. These data show that AK promotes the modulation of oxidative and antioxidative balance as a possible protective mechanism in the cell death produced by LPS in Müller's Glia enriched cells.
Key Words: RETINA, GLIA CULTURE, AK, LPS

Currently, with the increase in life expectancy of human populations, neurodegenerative diseases, commonly occurring with the advancing age, have become a source of serious concern. Thus, research into new ways of early diagnosis of neurocognitive disorders associated with diseases such as Alzheimer's and Parkinson's, as well as the improvement of the understanding of currently available clinical neurological diagnostic methods, has been promoted throughout the world. In this sense, this work proposes to investigate the existence of possible correlations between the results of exams used in clinical neurological investigation of patients diagnosed with neurocognitive disorder associated with these important neurodegenerative diseases (Alzheimer's and Parkinson's diseases). The results show that the measurement of the thickness of the nerve fiber layer of the perimacular retina, performed by optical coherence tomography, is a parameter that may not differ significantly between groups of patients and healthy subjects. On the other hand, the measurement of the amplitude of the spectroscopic signals generated by encephalic metabolites, performed by magnetic resonance proton spectroscopy, reveals encephalic changes that vary from region to region. In addition, the neuropsychological measure of cognitive functions, performed by the automated CANTAB battery, reveals that several aspects of these functions are impaired in these patients. Finally, Principal Component Analysis shows that, considering the set of variables obtained by tomographic and neuropsychological measurements, it is possible to observe a correlation between several of these variables. Thus, it is concluded that correlating the results obtained by different approaches may add potential in the interpretation of this casuistry, which would not be possible if we consider such data in an isolated way.

Systemic lupus erythematosus (SLE) is a chronic disease characterized by progressive tissuedamage. In recent decades, novel treatments have greatly extended the life span of SLE patients. This creates a high demand for identifying the overarching symptoms associated with SLE and developing therapies that improve their life quality under chronic care. We hypothesized that SLE patients would present dysphonic symptoms. Given that voice disorders can reduce life quality, identifying a potential SLE-related dysphonia could be relevant for the appraisal and management of this disease. We measured objective vocal parameters and perceived vocal quality with the GRBAS (Grade, Roughness, Breathiness, Asthenia, Strain) scale in SLE patients and compared them to matched healthy controls. SLE patients also filled a questionnaire reporting perceived vocal deficits. SLE patients had significantly lower vocal intensity and harmonics to noise ratio, as well as increased jitter and shimmer. All subjective parameters of the GRBAS scale were significantly abnormal in SLE patients. Additionally, the vast majority of SLE patients (29/36) reported at least one perceived vocal deficit, with the most prevalent deficits being vocal fatigue (19/36) and hoarseness (17/36). Self-reported voice deficits were highly correlated with altered GRBAS scores. Additionally, tissue damage scores in different organ systems correlated with dysphonic symptoms, suggesting that some features of SLE-related dysphonia are due to tissue damage. Our results show that a large fraction of SLE patients suffers from perceivable dysphonia and may benefit from voice therapy in order to improve quality of life

Chromoblastomycosis (CBM) is a mycosis by implantation, chronic, with a cosmopolitan distribution, caused by melanized fungi. After transcutaneous implantation, the propagules of the CBM agents present a unique cellular and morphological plasticity. The cellular differentiation results in the appearance of muriform cells. The treatment of this mycosis is a challenge due to the absence of a standard antifungal, resulting in several therapy methods (physical and pharmacological), used isolated or associated, with little clinical cure success. Amazon region has a vast biodiversity of vegetables that need to be better characterized as to their chemical composition and applicability in the treatment of different diseases. In this variety of plants, the fruit of Malpighia glabra Linn. (acerola) has a high content of vitamin C, also presenting vitamins of the complex B, A, anthocyanins and flavonoids, which stand out for having different biological and therapeutic actions already demonstrated both in vitro and in vivo. A major interest is currently focused on the biological activities of quercetin, belonging to the class of flavonoids, as it exerts multiple pharmacological activities, presenting unique biological properties that can improve mental and/or physical performance and reduce the risk of different infections. This study aims to evaluate the in vitro antifungal activity of M. glabra extract in conidia and muriform cells of Fonsecaea spp. The extract of M. glabra presented antifungal activity in both, conidia and muriform cells, of the evaluated strains. Much interest is now centered on biological activities of the flavonoid quercetin. In addition to the crude extract, the conidia of different strains were also sensitive to different dilutions of the extract. The minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (MFC) were evaluated. The geometric mean of the quercetin MIC for the conidia was 4.75 μg/mL and the geometric mean of the CFM was 11.31 μg/mL. Further study is needed so that M. glabra or quercetin, isolated or associated with another isolated component of the extract, may be used for the treatment of CBM in the future.

The pathophysiology of depression still remains not fully understood. And despite the contributions of the monoaminergic hypothesis to the understanding of neurobiological aspects of this disorder, studies have been carried out to investigate the role of neuroinflammation, polymorphisms in genes that influence inflammatory activity and monoaminergic receptor functions in the development of major depressive disorder (MDD). However, few studies have analyzed the role of upstream inflammatory pathways (such as the role of NFKB1 and PAR1 genes, which are capable of influencing transcription of proinflammatory cytokines) and of the alpha 2 adrenergic receptor encoding gene's polymorphism (ADRA2B gene) in individuals diagnosed with depression. Therefore, the objective of this study was to analyze the role of the INDEL type polymorphisms of NFKB1 (rs28362491), PAR1 (rs11267092) e ADRA2B (rs34667759) genes in the development of major depressive disorder. Twelve patients diagnosed with MDD and 145 healthy controls had blood samples collected and the INDEL polymorphisms of these 3 genes were genotyped by a single multiplex reaction. The multiplex PCR products were separated by capillary electrophoresis and the data analyzed in GeneMapper 3.7 software (Applied Biosystems). This research found a statistically significant association between depression and Del/Del genotype of the ADRA2B gene (p = 0.002): these individuals presented a 6.41 times greater chance of developing depression when compared to Del/Ins and Ins/Ins genotypes. There was no statistical significance between the INDEL polymorphisms of NFKB1 and PAR1 genes and depressive phenotype. Our results suggest that the INDEL marker of the ADRA2B gene (rs34667759), specifically the deletion allele, is a possible genetic biomarker of vulnerability for the development of MDD.

The riverside communities of the Amazon are vulnerable populations exposed to factors that are difficult to find in the populations of the rest of the country (from the bioavailability of Amazonian natural wealth to geographic isolation). However, little is known about the anthropometric characteristics and eating habits of these communities. The objective of this study was to conduct a study of the nutritional status and dietary intake of riparian communities in the Tapajós and Tucuruí regions, through the analysis of anthropometric parameters (Body Mass Index, Waist Circumference, Waist-Hip Ratio and Neck Circumference) , As well as food profile analysis. A total of 234 adult subjects were included in this study (143 from Tapajós and 91 from Tucuruí). The results showed that 77% and 65% of the Tapajós and Tucuruí populations, respectively, present 2 or more altered anthropometric parameters, showing the predominance of pre-obesity and obesity in these populations. Women had a higher risk of developing obesity-related diseases. The consumption of fruits in the Tapajós region (87.3%) and in the Tucuruí region (89%), as well as the consumption of fish (Tapajós 97.9% and Tucuruí 95.6%), And flour (Tapajos 86.6% and Tucuruí 86.8%). We also observed that the populations present healthy eating habits, but consume certain foods that would be influencing the current nutritional status, as well as the way of preparation. Studies that include these populations are scarce, and educational and public health measures are necessary to raise awareness of the improvement of eating habits, the importance of practicing physical activity, and to avoid behaviors such as Consumption of alcohol and smoking to avoid problems related to obesity.

Diabetes Mellitus (DM) is a disease that awake the interest of many health professionals. It is a chronic disease on a world scale, and over the years has become a matter of concern for public health. The disease is divided into diabetes type 1 and type 2, which causes a dysfunction in insulin / glucose physiology. This deregulation causes significant alterations in some biological events, among them, the cicatrization process.The appearance of an injury to a normal person triggers a cascade of cellular and biochemical reactions in order to repair the injured tissue. In patients with diabetes, the repair is slower. Several mechanisms are described as important factors in the delay of the healing process in diabetics, among them, excessive production of reactive oxygen species (ROS), reduction of nitric oxide (NO), reduction of the response to growth factors (GFs) and the insulin signaling pathway proteins. The search for therapeutical forms that can help the tissue repair process is in great demand, since the number of people with diabetes is increasing over the years. The Pracaxi seed extract is powerful dermatological healing, helps in hydration and cell renewal, important processes in healing, thus demonstrating positive perspectives in its use in diabetic patients' injuries. The objective of this project is to analyze the pharmacological effect of the topical application of the ketone extract of the Pentaclethra macroloba Wild (Pracaxi) seed in the process of tissue regeneration in diabetic animals. To evaluate the potential of the plant, a clinical picture of diabetes was initially induced in the animals through the alloxan drug, cytotoxic beta - pancreatic cells, then a skin lesion with the biopsy punch was generated in the dorsal region of the animals and subsequently the lesions Were treated with the pracaxi extract. After treatment, the effects and benefits of using the extract on skin lesions in diabetics will be evaluated.

Spinal cord injury (SCI) causes permanent loss of neurological function below the level
of injury, generating social and psychological physical consequences in patients. The
pathophysiology of SCI involves complex processes, such as hemorrhage,
excitotoxicity and inflammation, mainly generated by microglial cells. Despite
advanced knowledge of pathological mechanisms, effective and approved therapeutic
strategies for the treatment of lesions and their consequences are still lacking without
serious adverse effects. Cell therapy may represent a good therapeutic strategy
because it demonstrates good results in the modulation of the inflammatory
environment of the lesion and by probable mechanisms of differentiation. In the present
study, we investigated the action of bone marrow mononuclear cells (BMMC) in
incomplete lesions (hemisection to the right of the spinal cord, T8-T9 segment) after
42 days of injury (chronic lesion). The cells were from the injured animal itself
(autologous transplantation) and the transplantation was intramedullary, i.e. the cells
were inserted near the site of the lesion. In the present study, the functional effects of
transplantation were investigated through the BBB scale (Basso, Beatie and
Bresnahan), which allows the motor function of the hind legs of the animals to be
graded. The anti-inflammatory effects of BMMC were also investigated. Histological
and immunohistochemical techniques using Cresila Violet staining and anti-ED-1
(microglial marker / activated macrophages) and anti-GFAP (fibrillar astrocyte marker)
antibodies were used. Qualitative and quantitative analyzes were performed. For
quantitative analysis, the number of field activated astrocytes and macrophages /
microglia were counted using binocular microscope with counting gradient
(0.0625mm2) in a 40x objective. The counting averages and the standard deviations
obtained were plotted in Cartesian coordinates. The counting was as follows: on the
right side of the spinal cord (lesion side) and three fields per medullary region (ventral
funiculus - FV, dorsal funiculus - FD, lateral funiculus - FL, dorsal horn - CD, ventral
horn - CV and intermediate gray matter-SCI), totaling 18 counting fields per section.
Treatment with BMMC was not effective in improving the motor function of the injured
animals when we compared the treated and untreated animals (means and standard
deviations of the groups: false operated, n = 4, 21 ± 0, control, n = 4, 13,57 ± 3.88,
treated, n = 5, 15.07 ± 3.46). In the qualitative analysis by means of the staining of
Cresila Violet, treated animals presented better tissue preservation when compared to
the untreated animals. In the quantitative analysis of microglial activation, we observed
that treatment with BMMC reduced the activation of these inflammatory cells (control:
19.52 ± 7.79, treated: 10.04 ± 2.37), but did not significantly reduce the activation of
the astrocytes (Mean of the groups: control 17.74 ± 2.757, treated 14.46 ± 5.283). The
results suggest that further studies are needed to come up with an effective strategy
for patients with SCI. A possible combined treatment with other strategies may turn out
to be promising for patients' functionality.

Study of a chemotherapy delivery system, called LDE, with lipid composition similar to the natural low density lipoproteins of the body, denominated by the acronym LDL. LDEs have advantages over commercial chemical forms, since it is able to concentrate in the neoplastic tissues after injection into the circulatory chain, thus being able to target the tumors. LDE can be used as a "carrier" of paclitaxel (PTX) for possible reduction of toxicity and increase of its therapeutic action. The use of non-human primates as in vivo experimental models are of great importance in human health applications due to their anatomical, biochemical and phylogenetic similarities with human primates, generating results that can be interpreted more closely and safely to The phenomena in humans. The aim of the project was to evaluate the chronic toxicity of nanoparticles associated with to chemotherapy Paclitaxel (LDE-PTX) in individuals of the Sapajus apella species, based on the determination of hematological and biochemical parameters and their possible alterations. During the research 15 animals were used, divided into groups: Negative control (CN); Experimental (EXP1 and EXP2) where the animals received LDE-PTX intravenously two different doses of 175 mg / m2 and 250 mg / m2 respectively; and positive control (CP1 and CP2) where the animals intravenously received the drug in commercial form at the same doses used in the experimental group, respectively. Primates were accompanied for 6 cycles of chemotherapy, with interval of 3 weeks. Hematological and biochemical analysis was performed at each cycle through erythrogram and leukogram, alkaline phosphatase, total protein, albumin and globulin, total bilirubin and fractions, glycemia, amylase and serum lipase. E of the sodium and potassium eletrolytes were carried out in the serum of the animals during the collection days. Data were expressed as mean ± standard deviation and submitted to analysis of variance ANOVA, with Bonferroni post-test with significance for p <0.05, through BioEstat®5.3. The obtained results demonstrated advantages of the use of LDE-PTX, since the hematological tests demonstrate that there was a lower toxicity in all the chemotherapeutic cycles and the non-alteration of the majority of the biochemical parameters, demonstrate that the toxicity of the tested drug associated to LDE present smaller Effect toxic than its commercial version. It was concluded from the analysis of the results that hematological and biochemical toxicity was lower in treatment with PTX associated with LDE than treatment of PTX in its commercial form.

Aggression is a behavior that involves a simultaneous activation of physiological,
biochemical, neurological and behavioral components and emotions, such as anxiety
and anger. In humans, sports can be considered as a form of display because they
allow aggression to be expressed with a low probability of permanent damage to
subjects. The competitions have been used as models to evaluate the activation
produced by the different stages of competition, such as the outcome of the combat.
Judo has been used as a model of competitive aggression to evaluate the different
body responses in agonistic behaviors in humans, since it offers a context like those
studied in animal fights. The aim of this study was to evaluate the effect of win / lose
in the levels of anger and anxiety in regional judo fighters, male, linked to the Pará
Federation of Judo, Using the STAXI and IDATE psychometric scales, as well as
comparing these results with the Brazilian general population and a correlation
analysis to know the differences between the different components with the number
of strokes, using a pre/post fight evaluation and the filming of the fights. Differences
were found between winners and losers, as well as between fighters and the Brazilian
population; The losers presented higher levels of anger, while the anxiety was greater
for the winners.

Most central nervous system (CNS) diseases are incurable and extremely debilitating, acute spinal cord injury (LAME) causes permanent loss of neurological function below the level of the injury, causing severe physical consequences to patients. Trauma, falls and gunshot or joint weapon damage together make up almost 100% of the main mechanisms that cause LAME, as well as contribute to the high costs of the public health system. The pathophysiology of LAME involves complex processes such as vascular changes, excitotoxicity, lipid peroxidation and neuroinflammation, generated mainly by microglial cells. Despite the knowledge of pathophysiology, there is still no effective treatment for LAME. Thus, there is a mobilization of the scientific community to find a substance capable of promoting neuroprotection and, consequently, to reduce the sequelae of LAME below the level of the lesion. In this context, the Copaíba Resin Oil may represent a good therapeutic strategy. In this study, we investigated the antiinflammatory and neuroprotective effects of copaiba resin oil after hemisection of the spinal cord of rats. The animals were divided into experimental and control groups. Immunohistochemical techniques using anti-MBS-1 (neutrophil marker), anti-Iba-1 (microglial marker) antibodies, as well as staining with Cresila Violet were used. Qualitative and quantitative analyzes were performed. Copaiba resin oil proved effective in decreasing the recruitment of inflammatory cells to the area of spinal cord injury and promoted better preservation of the tissue area compared to the control group. As in the lowest neutrophil recruitment in treated rats compared to the control group (Treated group: 8.33 ± 0.66 (N = 3); Control group: 12.27 ± 0.28 (N = 3)) . Copaíba resin oil also promoted a reduction in the number of microglia in the area of spinal cord injury at different times (Treated group on day 1: 8.59 ± 1.72 (N = 3), Control Group on day 1: 35, (N = 3), Control Group on the 7th day: 65.77 ± 6.19 (N = 3)). These results suggest the antiinflammatory and neuroprotective effect of copaiba resin oil after LAME, revealing a promising strategy for the patient after LAME.

The mercury is an environmental contaminant which poses a great risk to human health. Exposure to this toxic metal occurs mainly through a diet contaminated by methylmercury (MeHg) in low concentrations and over a long period of time. Thus, in this study we propose an assessment of the effects of MeHg on the motor cortex in an animal model of chronic exposure and low dose, similar to dietary exposure in areas of high environmental toxicity of mercury. Adult rats were exposed to MeHg for 60 days with a dose of 0.04 mg/kg/day, while the control group received only the vehicle. After this period, they were subjected to behavioral testing in order to evaluate the motor performance after mercury exposure, and then sacrificed and evaluated for oxidative biochemical parameters (change in the concentration of nitrite - NO Lipid Peroxidation - LPO and Antioxidant Capacity Total) as well as evaluation of total deposits of mercury in the motor cortex and changes in cell density of neurons and astrocytes. Data were tabulated and statistically analyzed by Student's t-test (p <0.05). It was possible to observe total mercury deposits in the motor cortex, and deficits in motor parameters, with a reduction in the overall locomotion, on balance and increase in the number of failure, coupled with a significant increase in the levels of NO and LPO and decreased ability antioxidant full of animals exposed, reducing the population of astrocytes and neurons compared to control animals these findings suggest that exposure of adult animals to MeHg, even at low dose and chronically, causes changes in the motor cortex with damage to their functions.

Mercury is a highly toxic heavy metal, which can be found in organic and
inorganic elemental forms in the environment. The inorganic mercury has lower
liposolubility and consequently, lower absorption in the body, and lower
passage through the blood brain barrier. For this reason, exposure models
using inorganic mercury in rats to evaluate its effects in the central nervous
system are rare, mainly in adults. Therefore, we investigate the potential of low
concentration of mercury chloride (HgCl2), in a chronic exposure model to
promote motor changes associated to variables in the oxidative balance,
cellular cytotoxicity and apoptosis in the motor cortex of adult rats. For this
purpose, rats were exposed for 45 days to a dose of 0.375 mg/kg/day. After this
period, the animals were submitted to motor evaluation and then were collected
for measurement of total deposited mercury in neural parenquima, assessment
and quantification of cellular cytotoxicity and apoptosis and evaluation of the
oxidative balance. Furthermore, animals were perfused to evaluate the density
of mature neurons and astrocytes of the motor cortex. It was observed that
chronic exposure to inorganic mercury decreased balance and fine motor
coordination. In addition, we found that this exposition model led to cytotoxicity
and cell death by apoptosis, formation of deposits of mercury and oxidative
stress evidenced by the increase of lipoperoxidation and the concentration of
nitrites and decrease in total antioxidant capacity. Thus, our results provide
evidence that a exposition to inorganic mercury, even before his lower capacity
to cross the biology barriers, It is still capable to inducing motor changes
associated to cell death and apoptosis and oxidative stress in the motor cortex
of the adult rats.

This study evaluated effects of eccentricity and mode presentation on the multifocal visual evoked potential (mfVEPS) recordings extracted by second-order kernels and its possible contributions from parallel visual pathways. Nine subjects (22.5 ± 3.7 years-old) were studied. All the subjects had 20/20 or corrected visual acuity and no previous history of neuro-ophtahlmic diseases or degenerative diseases. The subjects were tested with non dilated pupil in a monocular way. All the experimental procedures agreed to the tenets of Helsinki and were approved by Committee for Ethic in Research of Nucleus of Tropical Medicine (023/2011 protocol, Federal University of Pará, Belém, PA, Brazil). A CRT monitor displayed a 22º radius, 60 sectors dartboard, each sector with 16 checks (8 white and 8 black), pattern mean luminance of 40 cd/m2. The pattern selection to be shown in each sector was temporally modulated according to a binary pseudorandom m-sequence. Two stimulation protocols were used and we called them as pattern reversal and pattern pulse. Stimulus was presented at five Michelson contrast levels (100%, 50%, 25%, 12.5%, and 6.25%) in two trials with increasing and decreasing contrast order. The subject was instructed to keep the eye in a red cross (1º) placed at the center of the screen. Veris 6.01 was used to configure the stimuli. mfVEPs were recorded with gold cup electrodes: the reference electrode was placed at the inion; the recording electrodes were placed at, 4 cm above the inion (channel 1), 1 cm above and 4 cm to the right of the inion (channel 2), 1 cm above and 4 cm to the left of the inion (channel 3). Ground surface electrode was placed at the forehead. Skin impedance was kept below 5 KOhm. Recordings were amplified 100.000x, band-pass filtered between 3 and 100 Hz. The Veris 6.1 performed an offline low-pass filtering at 35 Hz. Veris 6.1 was used to extract first (K2.1) and second (K2.2) slices from second-order kernels data from original channels. Using MATLAB routines three additional channels were computed from the subtraction of the three original channels. For each subject, a signal-to-noise ratio (SNR) evaluation was performed over the averaged data of two trials in each one of the 6 channels. We measured the RMS amplitude of signal and noise interval of each recording. Finally, we analyzed the waveforms with best SNR for each sector. Mean RMS amplitude for each of six eccentric rings (R1 and R6 are the inner and outer rings, respectively) and for all rings together as a function of stimulus contrast was modeled using Michaelis-Menten functions. Semi-saturation constant (C50) of the contrast-response function was used as indicator of response contrast gain. For pattern reversal protocol contrast-response functions from K2.1/K2.2 had the following C50 values: R1: 35,5% ± 9,3; R2: 26,5% ± 6,5; R3: 22,4% ± 8,8; R4: 18,4% ± 4,4; R5: 20,6% ± 9,3; R6: 26,7% ± 12 / R1: 38,4% ± 4,2; R2: 27,4% ± 7,4; R3: 20,2% ± 4,9; R4: 22,4% ± 4,2; R5: 18,7% ± 3,2; R6: 23,1% ± 8,9. For pattern pulse protocol contrast-response functions from K2.1/K2.2 had the following C50 values: R1: 0; R2: 44,7% ± 10,5; R3: 38,3% ± 12,1; R4: 45,8% ± 12,1; R5: 49,4% ± 16,1; R6: 47,8% ± 14,7 / R1: 0; R2: 50,2% ± 10,3; R3: 48,2% ± 11,1; R4: 28,5% ± 4,2; R5: 54,3% ± 16,2; R6: 0. Two contrast sensitivity mechanisms contribute to mfVEPs elicited by stimuli located in the central visual field, one mechanism with higher contrast gain (pattern reversal mfVEP) and other mechanism with low contrast gain (pattern pulse). For stimulus at the periphery visual field, mechanism with high contrast gain contributed to the generation of mfVEPs elicited by all stimulation modes.

The dipyrone or metamizole belongs to the family of the pyrazolones. It is one of the nonsteroidal anti-inflammatory compounds (NSAIs) most used, Brazil included, mainly due to its low financial cost. However, in some countries the sale of dipyrone is prohibited due to reported severe cases of agranulocytosis as a result of its use. Despite its high usage, studies showing genotoxic and cytotoxic effects of dipyrone in mammalian cells are scarce. Therefore, in the present study we will assess cell viability, genotoxic effects, cytotoxic effects (by apoptosis and necrosis induction) and the induction of reactive oxygen species (ROS) in VERO cells (a cell line obtained from red kidney of green monkey) exposed to dipyrone. Our results showed a significant reduction in viability of cells exposed to dipyrone by the MTT assay. A significant increase in damage index evaluated by comet assay was also observed, which indicate its genotoxic effects. In which concerns the cytotoxic effects of dipyrone, we observed a significant increase in the number of apoptotic cells using fluorescent dyes after 24h and 48 h of treatment with the drug. Ours results also showed that there was no significant difference in the induction of ROS generation after treatment of the cells with the drug assessed by the DCFH-DA technique. Thus, our work showed that dipyrone is both a genotoxic and cytotoxic drug to VERO cells in the assessed conditions.

Stroke results from the transitory or permanent reduction of cerebral blood flow. It can be
classified as hemorrhagic or ischemic. Ischemic stroke is responsible for around 87% of all
cases. This acute neural disorder is the second cause of mortality and disability around the
world and the main cause of death in Brazil. Since ischemic stroke in patients usually
results from a thrombotic or embolic occlusion of the middle cerebral artery (MCA),
experimental models of ischemia have been developed to mimic human stroke. There are
no neuroprotective drugs available for human stroke. It follows that research on
development of alternative neuroprotective drugs are of important clinical relevance. In
this study, we investigated the effects of betacaryophyllene, the main sesquiterpene present
in about 40% of the copaiba oil-resin composition, on microglial activation, astrocytic
reactivity and neuronal preservation following experimental MCAO in adult rats. Animals
were submitted to experimental stroke by microinjections of endothelin-1 (ET-1) and
treated (i.p) with betacaryophillene (N=4) or vehicle control (N=4) and perfused at 3 days
or 7 days post-MCAO. Gross histopathology was performed using cresyl violet staining.
Immunohistochemistry was used to assess neuronal loss (anti-NeuN), microglial activation
(anti-ED1) and astrocytosis (anti-GFAP). Numbers of NeuN+ and GFAP+ cells were
quantified in the ischemic striatum. Betacaryophyllene treatment reduced microglial
activation, increased neuronal preservation and decreased astrocytic reactivity at 7 days
post-MCAO. These results suggest that betacaryophylene modulates neuroinflammation
and is neuroprotective following experimental striatal. Considering that betacaryophyllene
is a natural dietetic extract already used in non-neural human diseases with antiinflammatory,
anti-microbial and anti-carcinogenic properties, its use as a neuroprotective
agent is a promising future therapy for human stroke.

The Peperomia pellucida (Piperaceae) is an herbaceous plant commonly found in the American and Asian continents. In the Amazon the species is known by the name of erva-de-jabuti. This plant is used in folk medicine to treat a wide range of symptoms and diseases such as conjunctivitis, headache, asthma, gastric ulcer, inflammation and arthritis. Pellucidin A is an isolated compound of the species Peperomia pellucida and this study aimed to analyze the antinociceptive and anti-inflammatory activity of this compound, as well as to elucidate its mechanism of action. For the assays, male albino mice (25-40 g) were used, which were initially treated with pellucidin A at the doses of 0.5; 1 and 5 mg / kg (i.p.) and subjected to locomotor evaluation by the open field test and animal models of acute pain, such as acetic acid-induced abdominal writhing tests, formalin tests and the hot plate test. The acetic acid-induced abdominal contortion test was realized to elucidate the mechanism of action in which the animals were treated at the standard dose of 5 mg/kg (i.p.) and for anti-inflammatory analysis of the compound was used model of granuloma induced by pellets of cotton, in which the animals were treated in the dose of 10 mg/kg (i.p.). The compound did not show capacity to change the ambulation of the animals at any of the administered doses. In the contortion test, pellucidin A was able to inhibit the number of abdominal writhings in 43% at the dose of 1 mg/kg, and 65% at the dose of 5 mg/kg. In the formalin test, an antinociceptive effect was observed at the dose of 5 mg/kg, with a 68% reduction in the lymph time of the animal's paw in the inflammatory phase, showing a similar response to Indomethacin used at a dose of 10 mg/kg as positive control for this phase. Animals treated with pellucidin A and subjected to the hot plate assay did not show any change in their latency time on the plate, showing a similar response to the animals treated just with the vehicle solution. For the elucidation of the action mechanism, the pellucidin A was administered at the standard dose of 5 mg/kg (i.p.) and associated with Indomethacin (5 mg/kg i.p.), NS-398 (10 mg/kg i.p.) cyproeptadine (0.5 mg/kg i.p.), naloxone (1 mg/kg i.p.) and L-NAME (5 mg/kg i.p.). The pellucidin A has shown a synergistic action when associated with cyproeptadine and L-NAME, with a decrease in the pattern of abdominal writhing by 97% when associated with cyproheptadine and 96% with L-NAME. In the analysis of the action of pellucidin A (10 mg/kg i.p.) in the granuloma test induced by cotton pellets, pellucidin A presented anti-inflammatory activity, reduced granuloma formation in 24% in the treated mice. The results confirm the hypothesis that pellucin A presents analgesic activity capable of interfering in the inflammatory process, acting as a possible glucocorticoid agonist.

Cardiovascular diseases have emerged as the leading cause of death in Brazil and in the world, representing a third of the deaths and the main spending on health care. Between 2000-2010, the number of deaths from cardiovascular disease in one hundred thousand inhabitants increased by 28% in the North, with dyslipidemia and metabolic syndrome among the main risk factors. These values become more worrying as it may be underestimated because of consequential underreported the geographical isolation of the region, which is characteristic of northern Brazil. Dyslipidemias correspond to changes in the plasma lipid profile, and represents a criterion for the diagnosis of metabolic syndrome. Metabolic syndrome can be defined as a set of metabolic changes such as hyperglycemia, dyslipidemia, hypertension and obesity. Recently, animal studies and clinical models have shown increased risk of atherosclerotic disease and hypertension with exposure to mercury. In the Tapajós River region, several studies have shown human exposure in riverine populations that consume fish contaminated with methylmercury. Also, recent data from our group show that the riverine communities of Tucuruí have high levels of mercury. The aim of this observational cohort study was to analyze the possible lipid abnormalities and the presence of metabolic syndrome in riverside communities in the Amazon region: Boa Vista do Tapajós, Barreiras, Pimental, Brasilia Legal, Fordlândia and Pedra Branca (Tapajós), Vila Cametá and community Ouro Verde (Tucuruí) with mercury exposure history. For this, the calculations were carried out in body mass index (by weight and height), blood pressure measurements, analysis of glycemic control (fasting blood glucose) and lipid, by plasma levels of triglycerides, total cholesterol, HDL and the calculations LDL, VLDL and HDL cholesterol did not the lipid. After application of the inclusion and exclusion criteria, a total of 337 adults of both sexes (220 of the Tapajos and 117 Tucuruí) were analyzed. High average levels of obesity and high frequency of individuals who had dyslipidemia were detected, especially in Tucuruí, where the frequencies were even higher than in the Tapajos. Also, high percentages of individuals were identified with metabolic syndrome (14% to 35% depending on the definition adopted). The criteria adopted by the NCEP have proved the most sensitive for the identification of metabolic syndrome (MS) in these populations. The main factor that contributes to the detection of the presence of MS was the low HDL level, present in 32% of individuals with MS. In Tapajós, the second and third most common factors were the high levels of triglycerides and glucose, however in Tucuruí was altered blood pressure and high triglycerides levels. In conclusion, our study provides, epidemiological data on the prevalence of dyslipidemia, overweight and obesity, high blood pressure and metabolic syndrome in adults bordering the Amazon. Adding to this, the epidemiological assessment of the lipid profile is an important tool for the promotion of health measures to prevent and reduce cardiovascular risk factors.

Açai (Euterpe oleracea Mart.) Is a typical northern palm of Brazil, rich in phenolics and
anthocyanins, substances with high antioxidant activity, anti-inflammatory and proven
beneficial health effects. Oxidative stress and inflammation are involved in the generation and
propagation of seizures, main clinical feature of epilepsy, and in the pathogenesis of
depression. In this work we investigated the potential neuroprotective effect, anticonvulsant
and antidepressant commercial samples of clarified açaí (CA). Only four doses of CA were
enough to increase latencies for myoclonic and tonic-clonic seizures and to reduce the total
duration of tonic-clonic seizures induced Pentylenetetrazole (PTZ). Eletrocorticográfics
changes induced by PTZ were prevented significantly by CA. In the depressive-like behavior
model induced by lipopolysaccharide (LPS), CA decreased immobility time and increased
significantly the sucrose consumption of animals, indicating that the CA has preventive
activity on the appearance of behaviors which are characteristic of clinical depression. Both
the PTZ model as LPS CA exhibited potent preventive activity against the oxidative stress.
CA prevented lipid peroxidation and elevated nitrite levels in the cerebral cortex,
hippocampus, striatum and prefrontal cortex. These results demonstrate for the first time that
acai is a fruit that exerts potent protective activity against the development of seizures, the
depressive-like behavior and oxidative stress, which is an additional protection for individuals
who consume this fruit.

Achilles tendon is the largest and strongest tendon in the human body, its excessive use induces microtrauma and activation of signaling pathways that lead to an inflammatory response. The ethanolic extract of Euterpe oleracea(açaí) is a natural product extracted from the fruit of the palm tree.Although evidence suggests an anti-inflammatory and antioxidant effect of this product, there is no data in the literature about such effects on tendon lesion. The aim of this study was to investigate the anti-inflammatory and pro-regenerative effects of ethanolic extract of Euterpe oleracea in a rat model of total Achilles tendon rupture. This study was approved by the Animal Research Ethics Committee (CEPAE-UFPA/206-14). The animals were divided into four groups (n = 24): control; vehicle (0.9% saline); E. oleracea extract (125 μg/mL ethanolic extract of Euterpe oleracea) and methylprednisolone (30 mg/ml). After the respective treatments, the tissue was analyzed at 7, 14 or 21 days post-injury (dpi) by immunohistochemistry with hematoxylin/eosin and collagen autofluorescence. Immunofluorescence for COX2 and measurement of nitrite levels by Griess method were performed at 7 dpi. Treatment with E. oleracea extract accelerated tissue organization and orientation of the cells, similarly to the anti-inflammatory steroid methylprednisolone. This natural product led to an early alignment in collagen fibers as well as in the overall matrix structure when compared to the other groups, which was observed at 7 dpi and maintained at both 14 and 21 dpi. Treatment with E. oleracea extract or methylprednisolone reduced COX2 labeling in comparison to the vehicle at 7 dpi. Reduction in nitrite tissue levels was observed at 7 dpi in groups treated with E. oleracea extract (20.80 ± 2.54 μm/ml) and methylprednisolone (19.40 ± 2.31 μm/ml) compared to vehicle group (29.33 ± 3.98 μm/ml). Treatment with E. oleracea extract improved tissue organization and reduced both COX2 labeling and nitrite levels, suggesting anti-inflammatory and antioxidant effects. Our findings highlight E. oleracea extract as a natural product with potential application in Achilles tendon repair.

Aging is associated with decreasing brain plasticity, especially after the closure of the critical periods of plasticity (a sensitive limited period in life of elevated brain plasticity). Some brain regions may be particularly affected by aging, such as prefrontal cortex (PFC), which has a key role in the organization of higher-order cognitive aspects, the executive functions, including attention, set-shifting, working memory, decision making, etc. Decline of plasticity in the PFC and the brain is attributed mainly to the appearance of a structure called perineuronal net (PNNs) which enwraps the cell body and dendrites of many classes of neurons. PNNs are extracellular matrix structures consisting of chondroitin sulfate proteoglycans, hyaluronan, link proteins and tenascin, and are involved in the control of experience-dependent cortical plasticity and the closure of critical periods. Degradation of PNNs with the enzyme Chondroitinase ABC (ChABC) restores juvenile forms of plasticity in the adult brain. Here, we examined the developmental time course of PNN formation in the medial PFC (mPFC) of male rats ranging in age from the seventh postnatal day (PND) to 11 months. We used the lectin Vicia villosa agglutinin that binds to glycosaminoglycan chains present in the PNNs. We also investigated whether the digestion of PNNs by bilateral injection of ChABC in the mPFC may open a new window of increased plasticity in adult rats, evaluated by two executive function tests: object recognition and spontaneous alternation. We found that immature PNNs were observed in PND 20 animals, but mature PNNs were seen only after PND 75-90 and a mature form appeared around 5 months of age. In addition, our results showed that enzymatic PNN removal promoted a significant increase in performance in the ChABC-treated animals in both behavioral tests. The present study reveals for the first time the temporal development of PNN formation in the rat mPFC. We also show that the degradation of PNNs with ChABC not only promotes plasticity but also potentiates cognitive abilities in adult animals.

Cyclosporine A is an immunosuppressive drug with known action on T cells of the immune system used in organ transplantation and autoimmune diseases. In the nervous system, cyclosporin A acts by inhibiting the action of Calcineurin, an important second messenger from pathway of signal transduction Nerve Growth Factor (NGF), resulting in hyperphosphorylation of the nuclear factor of activated T cells (NFAT), and downregulation of NGF, TrkA and other factors that participating in this pathway. The NFAT1-4 family are dependent isoforms of calcineurin, while NFAT5 isoform is independent. It has been demonstrated the neuroprotective role of Cyclosporin A via calcineurin dependent or independent. In this study, we evaluate the action of Cyclosporine A in the PNS system, that could be associated with levels of NGF, TrkA and an independent of calcineurin transcription factor (NFAT5) that interplay the plasticity of neuronal cells derived from Dorsal root ganglia (DRG) maintained in cultures. We use E10 DRG cultures supplemented with medium conditioned E9 Retinal treated with Cyclosporin A for 48 and 72 hours. Cultures enriched neurons were confirmed by calcium imaging method. The action of Cyclosporine A in the neuritogenesis was assessed by bright field microscopy, expression of NGF, TrkA and NFAT5 was performed by RT-PCR, intracellular accumulation of NGF was evaluated by immunofluorescence and the presence of TrkA in neurons. The viability test of the cultures treated or not with the concentrations of 1-40μM Cyclosporine A was performed by MTT method. The results show an increase of NGF levels in mixed cultures, and TrkA receptor and NFAT5 in cultures enriched in neurons following treatment with cyclosporine A. Given the importance of NGF pathway in the development and maintenance of the SNP, the use of Cyclosporin A have activity in the peripheral nervous system cells, which might be used in the clinic with new target for new therapies.

The Piroxicam is a NSAID that pharmacologically belongs to oxicam class and is indicated to treat various ailments such as rheumatoid arthritis, primary dysmenorrhea, endometriosis, among others. Its anti-inflammatory properties are well known and is related to its non-selective ability to reversible inhibition of COX, but it is known little about their cytotoxic activity and its effect on DNA. There are few data on the possible genotoxic effects of Piroxicam in mammalian cells. These effects can be monitored for the prevention and control of some adverse reactions and major side effects. This study was designed to investigate the possible genotoxic and cytotoxic induced in vitro by Piroxicam drug in kidney line of African green monkey (VERO). The viability of cells exposed to piroxicam was evaluated by MTT assay, cytotoxicity of piroxicam was verified by quantifying apoptosis and necrosis using fluorescent dyes (Hoechst, propidium iodide and fluorescein diacetate) and genotoxicity of piroxicam was evaluated by the comet assay. The results of the cell viability assay showed that Piroxicam reduces significantly (p <0.05) cell viability in the concentrations of 1.0 mM, 2.0 mM, 4.0 mM and 8.0 mM. It is also noted that piroxicam induced significant killing (p <0.01) by apoptosis in all concentrations tested, both as to 24h treatment 48h. In the case of the comet assay, there was no damage to the DNA in any concentration tested. The data support the idea that piroxicam has a cytotoxic activity, but has no genotoxic potential in the tested conditions.

The spinal cord is a component of central nervous system (CNS) with crucial functions for locomotion, motor skills, somatosensory and authonomic control. Spinal injuries are among the more serious and debilitating pathological conditions to human health with large worldwide. The use of experimental models of spinal cord injury (SCI) is pivotal to understandthe SCI pathophysiology as well as search for treatments to minimize the neurological deficits and improve functional recovery. In this work, we aimed to investigate the neuroprotective and anti-inflammatory effects of supercritical gergelim (Sesamum indicum L.) extract in the acute phase of SCI in adult rats. Male Adult rats were submitted to spinal cord (SC) hemissection at T8. The sham (non lesioned) and control animals were treated with 5% tween(veicle), while treated animals received intraperitoneal (i.p) injections of Gergelim extract (150 mg/kg divided in two doses per day). Animals were allowed to recovery and were perfused at 1, 3 and 7 days post-lesion. 20 μm sections were obtained using a cryostat and stained with methylen blue, hematoxylin-eosin (HE), trichromic of Gomori and cresyl violet for gross histopathology. In addition, sections were immunolabeled with specific antibodies against neutrophils (anti-MBS-1) and activated microglia/macrophages (anti-ED1). The muscle force was assessed through electromiographic records performed in both control and treated animals at 1 and 7 days postlesion. The control animals presented progressive SC cavitation concomitant with neutrophil recruitment and microglia/macrophage activation. The treatment with gergelim extract induced tissue preservation and considerable decrease of neutrophil recruitment at 1 and 3 days, which was confirmed by quantitative analysis (ANOVA-Tukey, p<0.05). The gergelim treatment also decreased the microglia/macrophage activation at 7 days (ANOVA-Tukey, p<0.05). The electromiographic records revealed that the gergelim treatment improved the muscular force in about 50% compared to control animals. The results suggest that black gergelim seed extract is anti-inflammatory, neuroprotective and induces muscle force recovery in adults rats submitted to acute SCI. Future studies should confirm that a phytotherapic obtained from black sesame extract can be used as possible neuroprotective agent for human SCI.

A malária é uma doença causada por protozoários do gênero Plasmodium e apresenta-se como um dos principais problemas de saúde pública no mundo. Para avaliar o quadro de malária, modelos murinos tem sido utilizado devido às suas similaridades entre as espécies infectantes para os camundongos e as espécies infectantes para o homem. O aumento na produção de espécies reativas de oxigênio e alterações na atividade de enzimas como a glutationa peroxidase e superóxido dismutase foram caracterizadas dentro do quadro clínico da doença, porém pouco se sabe a respeito da participação de moléculas antioxidantes como a glutationa na evolução da doença. Diante do exposto, o principal objetivo deste trabalho é avaliar o efeito da glutationa na evolução do quadro de malária murina e frente aos danos causados pela infecção com cepa ANKA de Plasmodium berghei (PbA). Para isso foram utilizados camundongos Balb-C, o qual foi inoculado (~106 de eritrócitos parasitados) via intraperitoneal. Os grupos foram divididos em: grupo malária (PbA) (n=6), grupo PbA + GSH 1mg (n=6), grupo PbA +GSH 3mg (n=6) e grupo PbA +GSH 8mg (n=7), tratados por 7 dias consecutivos. O desenvolvimento da doença foi monitorado diariamente pela determinação da sobrevivência, massa corpórea e a parasitemia foi monitorada a cada três dias em distensões sanguíneas, também foi analisado os cortes histológicos do tecido hepáticos e foi realizado a dosagem bioquímica das transaminases hepáticas. Nossos dados demonstraram que o tratamento com GSH (8mg/kg) acelerou a mortalidade dos animais infectados uma vez que entre o 13-14 dia pós infecção cerca de 43% dos animais evoluíram a óbito. No grupo infectado com PbA que não recebeu tratamento com GSH, uma diminuição semelhante (40%) só foi observada a partir do 23-25 dia pós infecção. Já em relação aos grupos PbA+GSH 1mg e PbA+GSH 3mg, não houve diferença quando comparado com o grupo PbA. Interessantemente, embora o tratamento com GSH 8mg tenha acelerado a mortalidade no grupo infectado, não observamos diferença significativa no nível de parasitemia dos quatros grupos analisados. Em relação a massa corpórea foi possível observar uma diferença entre o dia 0 e 24 em todos os grupos, porém quando analisado entre os grupos. Já no que diz respeito as análises histológicas e dosagens bioquímicas, podemos observar que ouve alterações tanto na histologia quanto na nas transaminases, sendo estas alterações mais expressas no grupo PbA que foi tratado com glutationa 8mg/kg do que no grupo PbA. Concluindo que a glutationa quando administrada via intraperitoneal acelera a mortalidade dos camundongos infectados com a cepa ANKA, porém essa mortalidade não está associada com aumento da parasitemia, indicando então que a mortalidade pode ser decorrente das alterações hepáticas.

Estudos recentes mostram que liberação de glutamato por células gliais hipotalâmicas é uma importante resposta fisiológica em situações de hiperosmolaridade. Além disso, estudos prévios apontam um marcante aumento dos níveis de adenosina no fluido intersticial renal após o aumento da ingestão de sódio. Neste contexto, o objetivo do presente estudo foi caracterizar a possível relação entre a liberação de adenosina e a liberação de glutamato em culturas primárias de astrócitos expostas à situação de hiperosmolaridade. Culturas de astrócitos hipotalâmicos obtidos de ratos da linhagem Wistar nos dois primeiros dias de nascidos,  foram expostas à solução hipertônica com sódio (340mOsm/L) nos tempos 3, 5, 10 e 15 minutos. Após o estímulo, o meio de incubação foi coletado e os níveis extracelulares de glutamato e adenosina foram determinados por Cromatografia Liquida de Alta Eficácia (CLAE). Afim de avaliar a relação entre estes compostos em situações hiperosmóticas, utilizou-se o tratamento das culturas com Adenosina, com R-PIA um agonista do receptor A1, bem como com glutamato e agonista do receptor tipo NMDA. Nossos resultados demonstraram elevação significativa dos níveis extracelulares de glutamato após o estímulo hiperosmótico com um pico em 5 minutos. Similarmente, observamos o aumento nos níveis de adenosina no meio de incubação após 10 e 15 minutos. O tratamento com glutamato induziu aumento nos níveis extracelulares de adenosina após 15 e 20 minutos em meio iso-osmótico. A exposição ao NMDA não induziu a liberação de adenosina e em nenhuma das concentrações utilizadas. Os pré-tratamentos com adenosina e o agonista A1 R-PIA impediram a liberação de glutamato induzida por hiperosmolaridade.  Nossos resultados mostraram também que o efeito do estímulo na liberação de glutamato e adenosina é dependente de sódio, e apresenta uma resposta específica para astrócitos do hipotálamo que pode ser modulada através da ativação do receptor A1 de adenosina. 

O Brasil é um País em período de transição demográfica com aumento expressivo da população acima de 65 anos, o que requer mudanças nas políticas públicas destinadas à saúde. O início precoce de cuidados específicos com a população adulta e jovem visando o envelhecimento bem-sucedido, pode representar redução futura de gastos públicos e menor incidência de doenças associadas ao envelhecimento, como as demências. Para prover subsídios às políticas de saúde baseadas em evidências, o presente trabalho investigou os efeitos do condicionamento físico no desempenho em testes neuropsicológicos automatizados selecionados para mensuração de funções de aprendizado, memória visuoespacial e linguagem. Foram avaliados 109 adultos jovens saudáveis de ambos os sexos, submetidos à anamnese; avaliação cognitiva global empregando o Mini exame do estado mental, testes de linguagem (incluindo fluência verbal e a lista de palavras da Bateria CERAD) e testes neuropsicológicos automatizados (Bateria CANTAB); avaliação da aptidão física (avaliação indireta do condicionamento cardiorrespiratório, resistência de membros inferiores, avaliação da agilidade, mensuração de índices perimétricos e antropométricos). Com base na estatística multivariada através da análise de conglomerados (método de Ward, Distância Euclidiana) os voluntários foram reunidos em três grupos, pareados por idade e escolaridade, para proceder-se o teste ANOVA um critério ou o Kruskall-Wallis, em caso de amostras com variâncias desiguais. Também foi realizada a análise de correlação, componentes principais e análise discriminante, a qual mostrou que o condicionamento cardiorrespiratório foi a variável que mais contribuiu para formação de agrupamentos. O nível de significância foi fixado em valores de p≤0,05. Foram constatadas diferenças significativas nos testes de fluência verbal semântica; nos testes de aptidão física incluindo frequência cardíaca de repouso, condicionamento cardiorrespiratório, resistência de membros inferiores e avaliação da agilidade e em testes neuropsicológicos da Bateria CANTAB (aprendizagem pareada - PAL e tempo de reação - RTI). A análise de correlação demonstrou apenas correlações fracas. Os resultados obtidos no presente estudo indicam que o desempenho em testes neuropsicológicos não pode ser predito pelo condicionamento físico de adultos jovens praticantes ou não de exercício físico regular. Entretanto, o condicionamento físico demonstrou estar associado com melhor desempenho em tarefas de atenção, memória visuoespacial e de aprendizado, mensuradas através do PAL e RTI.

A medula óssea é um tecido de aspecto gelatinoso que contém células hematopoieticas responsáveis pela proliferação e diferenciação das células sanguíneas circulantes. A proliferação de monócitos na medula óssea e a diferenciação destas células em macrófagos desempenham papel crucial para a resposta imune. Neste contexto, a busca por medicamentos que potencializem a resposta imune inata se faz necessária para restaurar a homeostasia e resposta imune. O Ácido Kójico (AK) é um metabólito secundário obtido de fungos do gênero Aspergillus que apresenta várias aplicações (aditivo alimentar, cosméticos, agente antitumoral, radioprotetor e ativador de macrófagos), por este motivo, este trabalho tem o objetivo de avaliar a ação imunomodutatória do AK em células da medula óssea de camundongos. Estas células foram obtidas a partir de fêmures de camundongos, tratadas com AK na concentração de 100 μg/mL e mantidas em cultura por 24-96 horas. Foi possível observar através da microscopia óptica que células mononucleares da medula óssea tratadas com AK promoveram o aumento da adesão celular, maior espraiamento celular, maior volume citoplasmático e grande quantidade de vacúolos. Para confirmar estes resultados, foi analisado por Western blot a via de sinalização Akt. AK foi capaz de ativar esta via, que apresenta papel regulatório muito importante no desenvolvimento e diferenciação celular. Também foi detectado por citometria de fluxo o aumento de F4/80 e do CD11b, seguido da diminuição do CD11c em células tratadas por 96 horas, mostrando que o AK é capaz de induzir o processo de diferenciação das células da medula óssea em macrófagos e não em células dendríticas. A análise microbicida revelou que o AK também potencializou a fagocitose e aumentou a produção de ânion superóxido, entretanto, não promoveu o aumento na produção de óxido nítrico. Além disso, não foram observados efeitos citotóxicos nas células tratadas com AK quando comparadas as células não tratadas. Assim, o AK parece atuar como agente imunomodulador, sendo capaz de induzir as células da medula óssea durante o processo de diferenciação da linhagem monocítica.

Dados estatísticos apontam AVE como a segunda maior causa de morte e primeira causa de incapacidade dentre todas as demais doenças no mundo. O AVE isquêmico (AVEi) é responsável por cerca de 87% de incidência dos casos de acidentes vasculares encefálicos. Os atuais modelos para estudos de AVE baseiam-se em comprometimento cerebrovascular. Um modelo experimental, capaz de mimetizar a fisiopatologia isquêmica, amplamente utilizado, é o de isquemia induzida por Endotelina-1 (ET-1). No curso isquêmico, a inflamação atua na contenção do infarto ocasionado pelo AVEi, e em contrapartida a intensidade da resposta inflamatória influencia na neurodegeneração e consequentemente na perda funcional. A terapia celular autóloga, com células mononucleares da medula óssea, promove modulação na neuroinflamação, sendo oportuna durante um evento isquêmico para diminuição de perda tecidual e funcional. No presente trabalho, utilizamos um modelo experimental de AVEi focal para avaliar os efeitos morfofuncionais do implante autólogo de células mononucleres da medula óssea (CMMOs) sobre as alterações morfofuncionais relacionadas ao AVEi. Demonstramos, neste estudo, que os transplantes autólogos de CMMO em períodos agudo ou agudo e subagudo, de evento isquêmico, promoveram neuroproteção e modulação inflamatória capazes de repercutirem em preservação e recuperação funcional em atividades especificas. Demonstramos, também, que o tratamento reforçado em período subagudo, do evento isquêmico, foi capaz de promover aumento das melhoras morfofuncionais promovidas pelo transplante autólogo em período agudo.

Os polimorfismos COMT Val158Met e ZDHHC8 rs175174 têm recebido papel de destaque no
estudo molecular da esquizofrenia não apenas por estarem localizados no principal locus de
suscetibilidade da doença, 22q11, mas também por relacionarem-se, respectivamente, ao estado
dopaminérgico do córtex pré-frontal e à atividade de diversas proteínas em células neuronais.
Para avaliar a influência dos genótipos polimórficos na esquizofrenia, genotipamos por PCR em
tempo real 130 pacientes e 175 controles de uma população do Norte do Brasil. Nossos
resultados indicaram uma ausência de associação entre ambos os polimorfismos com a chance de
esquizofrenia na população estudada. Todavia, quando categorizada por sexo, encontramos uma
associação dicotômica entre o genótipo Met/Met do polimorfismo COMT Val158Met e a
suscetibilidade à esquizofrenia, conferindo uma chance maior da doença em homens (OR =
10,76; IC 95% = 2,09–55,34; p = 0,004) que em mulheres (OR = 0,23; IC 95% = 0,07–0,69; p =
0,009). Além disso, a análise de variância revelou uma associação dos genótipos Val/Met (COMT
Val158Met) e GG (ZDHHC8 rs175174) com maiores médias de idade de início da esquizofrenia.
Nosso estudo suporta a hipótese de associação dependente de gênero do polimorfismo COMT
Val158Met com a esquizofrenia, além de apontar uma influência de ambos os polimorfismos
estudados com a idade de início da doença.

O potencial cortical provocado visual tem sido utilizado para avaliar a visão espacial de luminância. A observação prolongada de um estímulo visual leva a uma série de mudanças na resposta neural em diferentes níveis de processamento do sistema visual. Os resultados destes estudos tem levado à compreensão de como o córtex visual primário processa informações espaciais. Muito tem sido sugerido sobre a ativação das vias paralelas M e P para a contribuição das respostas visuais corticais à partir do uso de estímulos que ativariam preferencialmente uma ou outra via. Uma abordagem para se estudar as interações da atividade atribuída às vias paralelas visuais M e P sobre as respostas corticais poderia ser a aplicação de estímulos que promovessem a adaptação preferencial de uma das vias ou mesmo de ambas e deixar que a via remanescente pudesse se expressar na resposta visual cortical. O objetivo deste estudo é avaliar os efeitos da adaptação ao flicker para estímulos de contraste de luminância sobre respostas corticais visualmente provocadas em várias condições favoráveis à ativação diferencial ou conjunta das vias paralelas M e P, levando a um aumento ou diminuição das respostas corticais. Foram avaliados 8 sujeitos com visão normal e acuidade normal ou corrigida 20/20. Foram utilizadas várias condições de estimulação, as quais serão três condições de estimulação sem adaptação visual, contendo apenas os estímulos testes, redes senoidais em 0,4 cpg, 2 cpg e 10 cpg com taxa de reversão espacial de 180 graus de 1 Hz (condições controle). As demais condições apresentaram um estímulo de adaptação que será uma máscara gaussiana bidimensional que variará a luminância no tempo cosenoidalmente (flicker) com modulação temporal de 5 Hz, 10 Hz e 30 Hz. O experimento consistiu em apresentar um estímulo de adaptação durante 8 s seguido por um estímulo teste durante 2 s. As respostas corticais foram registradas sobre o couro cabeludo acima do córtex occipital e foram registradas apenas durante a apresentação do estímulo teste. As respostas corticais foram avaliadas no domínio do tempo e das frequências temporais. No domínio do tempo, medido a latência e a amplitude do componente P1 (pico-linha), enquanto no domínio das frequências temporais foram avaliadas as amplitudes das bandas de frequências alfa, beta e gama presentes no registro. As respostas para os estímulos testes foram comparadas entre as condições sem adaptação e com adaptação visual ao flicker. O principal resultado foi que a adaptação visual ao flicker ocorreu de forma diferenciada no domínio das frequências espaciais. Os resultados indicam que o componente P1 foi encontrado em todas as condições de estimulação e adaptação ao flicker na frequência espacial mais baixa (0,4 cpg) em todas as condições temporais. Os resultados também indicam que ocorreu uma diminuição da energia da banda alfa na mesma condição de 0,4 cpg e um aumento da banda gama. Este trabalho concluiu que a adaptação ao flicker levou à diminuição da amplitude do potencial cortical provocado visual causado pela diminuição da energia das oscilações alfa e aumento da energia na banda gama em 0,4 cpg, representando uma modificação do balanço entre as duas vias visuais M e P nas células do córtex.

As lesões tendíneas causam forte impacto sobre as pessoas em decorrência da dor e limitação funcional dela resultante. Após a lesão, o tecido passa a apresentar uma rede de nervos. Adicionalmente, há indícios da ocorrência de plasticidade central na medula após a lesão. Dentre os fatores moleculares envolvidos no reparo da lesão, o óxido nítrico (NO) é implicado na remodelagem tecidual, contudo seus efeitos ainda não são bem compreendidos. A proposta deste estudo é averiguar a existência de plasticidade central e a influência do NO na plasticidade periférica, limitação funcional e regeneração tendínea em modelo murino. Para estudar os efeitos do NO na plasticidade periférica, utilizamos animais controle (CTRL, sem lesão) ou tratados com salina (SAL, NaCl 0,9%), L-nitro-arginina-metil-éster (L-NAME, inibidor da síntese de NO) ou nitroprussiato de sódio (SNP, doador de NO) em dias alternados até o 21º dia pós-lesão (DPL). Para avaliar a ocorrência de plasticidade central (segmento L5), apenas a lesão foi realizada e a medula coletada em 2 ou 21 DPL. Analisamos a integridade e a organização tecidual nas amostras de tendão por H&E, microscopia eletrônica de transmissão e imunofluorescência, que também foi usada para avaliar a plasticidade periférica. Para verificar a recuperação funcional do tendão, determinamos o índice funcional de Aquiles, o ângulo articular e o campo aberto. No estudo da medula espinhal, investigamos a reatividade glial e o envolvimento neuronal após a injúria através de colocalizações com o indicador de ativação celular c-Fos. Os achados desta pesquisa mostram que a inibição do NO promove a organização tecidual em associação ao aumento da síntese, secreção e deposição de colágeno. Além disso, a administração local de L-NAME parece favorecer a diferenciação celular para tipos morfológicos análogos a tenócitos e melhorar a organização de ramos nervosos por dentre a malha de colágeno em correlação com a recuperação funcional em 21 DPL. Por outro lado, o aumento nos níveis de NO através de SNP promoveu uma piora em quase todos os parâmetros analisados. Nossos dados mostram ainda que a injúria tendínea desencadeia um processo de plasticidade central com aumento da reatividade glial em 2 DPL e da ativação celular ipsilateral à lesão em 2 e 21 DPL. Em suma, nossos achados indicam a ocorrência de plasticidade central após a lesão tendínea e o favorecimento do reparo tecidual e da plasticidade periférica através do bloqueio nitrérgico, revelando aspectos fundamentais da recuperação tecidual que podem representar novos alvos para uma nova abordagem terapêutica em lesões tendíneas.

A maculopatia autossômica recessiva de Stargardt se caracteriza pela perda progressiva
simétrica da visão na região central do campo visual em indivíduos entre a primeira e segunda
décadas de vida. Também fazem parte do diagnóstico clínico a presença de lesões maculares
pontuais de coloração amarelo-esbranquiçadas encontradas nas regiões foveal e parafoveal,
além da deposição de lipofuscina gerando hipofluorescência e atrofia córiocapilar e do
epitélio pigmentado da retina. A acuidade visual dos portadores da degeneração de Stargardt
decresce com o seu progresso e tende a se estabilizar entre 20/200 (1,0 logMAR) a 20/400
(1,3 logMAR). Esta tese teve como objetivos a investigação da ocorrência de associações
entre as variantes alélicas (mutações) e os níveis de expressão do gene ABCA4 com a
morfologia dos granulócitos periféricos e os fenótipos clínicos, eletrofisiológicos e de
estrutura da retina em pacientes portadores da maculopatia de Stargardt. Nos onze sujeitos
selecionados foram identificadas quatro variantes do tipo não-sinônimas e três do tipo
sinônimas. A combinação alélica L1395P/D1817E foi encontrada em 64% dos 22
cromossomos analisados sugerindo a ocorrência do efeito do fundador. Não foi possível a
associação entre os genótipos e os fenótipos analisados. Os valores diferenciais de expressão
do gene ABCA4 obtidos entre pacientes e grupo controle, bem como a prevalência de
neutrófilos bastonados na circulação sanguínea periférica sugerem a possibilidade de servirem
como biomarcadores para Stargardt. As imagens retinográficas e angiográficas obtidas
permitiram a classificação em estágios I, II e III de comprometimento retiniano nos sujeitos
investigados. O valores de espessura da região central da mácula dos pacientes foram bem
menores do que aqueles obtidos para os controles, evidenciando a perda da camada de
fotorreceptores. Os achados eletrorretinográficos de campo total em função do tempo de
adaptação ao claro possibilitaram a caracterização das perdas funcionais nos sujeitos
investigados.

Apesar da considerável incidência, estudos de alterações genéticas nos genes
TP53, PTEN, IDH1 e IDH2, em tumores não gliais, são raros e, em alguns casos,
inexistentes. Os tumores não gliais são classificados geralmente como benignos e
raramente evoluem à malignidade, apresentando diferentes classificações,
incidências e localizações. Os genes supressores tumorais e de resposta a danos ao
DNA, TP53 e PTEN, estão entre os genes mais frequentemente mutados em
tumores humanos. Os genes IDH1 e IDH2 estão envolvidos no metabolismo celular
e, também, foram encontrados frequentemente mutados em gliomas, melanomas e
leucemias, sendo atualmente considerados como bons marcadores em gliomas.
Foram realizadas análises de alterações genéticas nos genes citados, a fim de
verificar se estão associados à etiologia e/ou progressão de tumores não gliais do
Sistema Nervoso Humano (SNH). Foram utilizadas as técnicas de PCR-SSCP para
amplificação da região de interesse e triagem mutacional das amostras para
posterior sequenciamento. Foram analisadas 37 amostras de tumores não gliais (14
schwannomas, 3 Meningiomas, 4 Meduloblastomas, 2 Neurocitomas e 14
Metástases do Sistema Nervoso Central (SNC). Somente o gene IDH1 apresentou
polimorfismos na SSCP em 12 (32,4%) amostras, sendo, então, submetidas ao
sequenciamento. No entanto, as reações de sequenciamento foram satisfatórias em
apenas em 5 amostras, entre as polimórficas, (1 metástase, 1 meningioma e 3
schwanomas,). Análises dessas 5 amostras identificaram diferentes mutações, uma
delas, presente em todas, uma transversão T→A no éxon 4 do códon 106 do gene
IDH1, resultando na substituição do aminoácido treonina por serina. Foram, também,
identificadas outras mutações em regiões não codificantes (íntron 4) do gene IDH1
em duas dessas amostras. As mutações encontradas em nosso estudo ainda não
haviam sido relatadas na literatura. Nossos resultados indicam a participação do
gene IDH1 na patogênese desses tumores.

A Ordem Rodentia representa a mais numerosa ordem de mamíferos, com cerca de 42% das espécies conhecidas atualmente. Os roedores apresentam 2.227 espécies, 468 gêneros e 33 famílias recentes, sendo este último elevado para 50 se forem consideradas as famílias extintas. A enorme variação na morfologia, na diversidade de habitats e climas e na alimentação são as causas desta Ordem ser mais numerosa e melhor sucedida evolutivamente entre as ordens de mamíferos. O gênero Oecomys pertence à subfamília Sigmodontinae (Cricetidae, Rodentia) com aproximandamente 16 espécies descritas, distribuídas em floresta tropical e subtropical do Centro e do Sul da América. Estudos citogenéticos prévios sugerem que o gênero Oecomys apresenta uma grande diversidade cariotípica, com o número diplóide variando entre 58 e 86. No presente trabalho foram analisados, por meio de técnicas citogenéticas convencionais e pintura cromossomo multidirecional (Sondas cromossômicas de Hylaeamys megacephalus – HME), foram analisados 18 exemplares de Oecomys, sendo quatro identificados como da região metropolitana de Belém, Pará ; dois no Município de Santa Bárbara, Pará; cinco  na região de Carajás, Pará e 7 na região do Calha Norte, Pará. Os exemplares do Parque Ambiental de Belém apresentaram 2n=72 e NF=76 e foram identificados como O. paricola. Os exemplares de Santa Bárbara apresentaram 2n=70 e NF=74 e foram identificados como O. paricola. Os exemplares de Carajás apresentaram 2n=70 e NF=72 e foram identificados como O. paricola. Os exemplares coletados do Calha Norte apresentaram 2n=62 e NF=80 e foram identificados como O.auyantepui.  Os citótipos descritos para O. paricola apresentaram diferenças em 5 picos de HME hibrizados, evidenciando 3 rearranjos para esta espécie. Para O. auyantepui foram identificados 5 rearranjos.  As diferenças cromossômicas encontradas para O. paricola de diferentes regiões geográficas sugere que estes citótipos pertencem a espécies crípticas, o que é caracterizado pela ausência de diferenças significativas morfológicas e moleculares, podendo os rearranjos cromossômicos ser a causa do processo de especiação.  Desta forma, O. paricola representa um complexo de espécies onde os indivíduos desta espécie estão se diferenciando independentemente um do outro, e ainda não houve tempo suficiente para fixação de diferenças morfológicas e moleculares.

Os testes Colour Assessment and Diagnosis (CAD) e Cambridge Colour Test (CCT) têm sido amplamente utilizados em pesquisas básicas e clínicas, devido à alta sensibilidade e especificidade de seus resultados. Estes testes utilizam diferentes paradigmas de estimulação para estimar os limiares de discriminação de cor. Pouco se sabe sobre a relação de cada paradigma na avaliação da discriminação de cor nesses testes. Sendo assim, este trabalho objetiva comparar os parâmetros de avaliação da discriminação de cor estimados pelos testes CAD e CCT em sujeitos tricromatas e com discromatopsia congênita. Foram avaliados 59 sujeitos tricromatas e 38 sujeitos discromatópsicos (16 protans, 22 deutans) com idade média de 26,32 ± 8,9 anos. Foram testados 66 sujeitos nos testes CAD e CCT, 29 sujeitos no teste CAD e 2 sujeitos no teste CCT. O fenótipo da visão de cores de todos os sujeitos foi determinado através de uma bateria de testes psicofísicos e a estimativa dos limiares de discriminação de cor foi avaliada pelos testes CAD e CCT. Os dados de limiares de discriminação de cor foram ajustados a funções de elipse. Os critérios analisados para cada sujeito foram: a área da elipse, o ângulo de rotação e tamanho dos vetores protan, deutan e tritan. Para cada um dos parâmetros foi realizada: estatística descritiva, análise da dispersão dos parâmetros entre os testes CAD e CCT e dos parâmetros em conjunto, razão entre os parâmetros, correlação dos parâmetros a três modelos matemáticos e análise de concordância. Os parâmetros de área e tamanho dos vetores deutan e tritan do subgrupo tricromata; área e tamanho do vetor tritan do subgrupo protan; e tamanho dos vetores protan e tritan do subgrupo deutan apresentaram equivalência entre os resultados de ambos os testes. Os parâmetros de área, ângulo de rotação e tamanho dos vetores protan e tritan apresentaram concordância de medidas entre os testes CAD e CCT. Fatores como as localizações distintas das coordenadas centrais dos testes CAD e CCT e a disposição espacial dos vetores no espaço de cor da CIE 1976 no teste CCT podem ter influenciado na determinação de limiares de discriminação cromática de ambos os testes. Apesar de utilizarem paradigmas distintos na configuração da estimulação, os testes CAD e CCT são equiparáveis.

O acidente vascular encefálico (AVE) é a segunda maior causa de morte no mundo e a principal
no Brasil, sendo que 87% dos AVE ocorrem por processos isquêmicos (AVEI). O consumo
crônico de etanol, que se inicia geralmente na adolescência, é reconhecido como um fator de
risco independente para a elevação da morbidade e mortalidade por AVEI. Apesar de que
casos que combinem as duas patologias sejam relativamente frequentes, não há dados
disponíveis em modelos animais ou clínicos que demonstrem a qualidade ou mecanismos de
interação entre as duas morbidades, e tão pouco suas consequências sobre a intervenção
terapêutica. Considerando então os recentes estudos que propõem a minociclina como nova
ferramenta terapêutica para o tratamento do AVEI, este estudo teve por objetivo investigar a
interação entre a Intoxicação Alcoólica Crônica (IAC) iniciada na adolescência e o AVEI em
córtex motor na fase adulta em ratos, e os efeitos do tratamento com minociclina sobre esta
interação, usando parâmetros comportamentais, celulares e moleculares. Ratas Wistar (de 35
dias de idade) foram expostas cronicamente a etanol (6,5 g/kg/dia, 22,5% m/v) ou água por
55 dias. Um dia após o fim da IAC, foi induzida isquemia focal no córtex motor com endotelina-
1 (ET-1), seguindo-se sete dias de tratamento com minociclina ou salina. Ao final deste período
os animais foram testados em modelos de campo aberto e rota rod. A seguir, os animais foram
sacrificados e o córtex dissecado para avaliação dos níveis de nitritos e de peroxidação lipídica.
De cada grupo, alguns animais foram perfundidos e o córtex motor submetidos à analise
histológica, para avaliação do dano, e histopatológica, para a morte neuronal (anti-NeuN),
ativação microglial/macrófagica (Anti-ED1) e astrocitária (anti-GFAP). A intoxicação por etanol
a partir da puberdade até a idade adulta potencializou os danos causados pela isquemia,
causando grandes perdas na capacidade de iniciar e gerir os movimentos, bem como na
coordenação e força motora em comparação aos animais isquêmicos pré-tratados com água.
Estas manifestações foram acompanhadas de aumento da perda neuronal, redução do
número de células ED1+ e GFAP+ e maiores níveis de nitritos e peroxidação lipídica. O
tratamento com minociclina foi eficiente em prevenir/reverter as perdas motoras e danos
teciduais induzidos pela isquemia focal, inibindo também a elevação dos marcadores de
estresse oxidativo. A IAC tanto isoladamente como sucedida pela isquemia focal, modificaram
o desfecho do tratamento com minociclina. Os nossos resultados indicam que a intoxicação
com álcool durante a adolescência agrava o déficit motor e danos no tecido em animais
sujeitos a isquemia focal no córtex motor. Este processo parece estar associado com a
ativação microglial/ astrocitária, mas principalmente com o estresse oxidativo. Mostra ainda
que o histórico prévio de IAC iniciado na adolescência interfere significativamente no
tratamento da isquemia cerebral com minociclina.

Aluminum (Al) is the third most abundant metal in the earth's crust, being present in large amounts in soil and water, its high bioavailability makes it an important environmental contaminant. Al is considered a neurotoxic agent and accumulates in the nervous system, being this behavior associated with several neurodegenerative diseases. However, little is known about its effects at doses similar to human consumption in the nervous and biochemical systems. Thus, this study investigated the effects of chronic exposure to aluminum chloride (AlCl3) on cognition, motor behavior and oxidative stress. For this, adult Wistar rats were divided into three groups: Al1 (8.3 mg / kg / day), Al2 (5.2 mg / kg / day) and Control (Distilled water) being exposed orally for 60 days. After the exposure period, behavioral, histological, oxidative stress parameters and quantification of aluminum levels in the blood were performed. There were no changes in motor behavior, there was change in only one exploratory parameter and in cognition. No differences were found in the population of the purkinje neurons between the experimental groups. Exposure to Al increased levels of this metal in the blood, also altering the parameters of oxidative biochemistry. Thus, we can affirm that exposure to Al in rats, at doses equivalent to urban exposure and in potentially safe doses are capable of promoting breakage of blood homeostasis, altering hippocampal biochemical balance, generating a state of oxidative stress and cognitive damage, not being able to promote significant changes in the cerebellum and motor parameters.

O crescente consumo de bebidas com elevado teor de cafeína pode resultar no
aparecimento de sintomas provenientes do transtorno de ansiedade induzida por essa
droga. Atualmente, tem-se utilizado a cafeína como um indutor farmacológico do
comportamento tipo ansiedade e essa indução pode facilitar a melhor compreensão da
relação entre alterações comportamentais e os mecanismos de ação envolvidos nesse
efeito, portanto o presente trabalho propôs que a via nitrérgica poderia ser um
mecanismo chave para explicar os efeitos comportamentais produzidos pela cafeína e
que esses efeitos poderiam ser revertidos por um antioxidante, logo, no presente
trabalho nós tivemos como objetivo avaliar o possível efeito do L-NAME e do
-
tocoferol no comportamento tipo ansiedade ampliado pela cafeína nos testes de
preferência claro/escuro (PCE) e distribuição vertical eliciada pela novidade (DVN) em
Daniorerio. Foram utilizados peixes da espécie Daniorerio(n=178) subdivididos nos
seguintes grupos experimentais: SAL – salina 0,9%; CAF – cafeína 100 mg/kg; DMSO
– dimetilsulfóxido 0,1%; L-NAME - (N-Nitro-L-arginina-metil éster hidrocloreto) 10
mg/kg; TF –
-tocoferol 1 mg/kg (receberam apenas uma injeção por i.p); SAL + SAL;
DMSO + SAL; SAL + CAF; L-NAME + SAL; L-NAME +CAF; TF + CAF (receberam
duas injeções seguidas, uma injeção de cada substância na forma de cotratamento, por
i.p). Os animais foram submetidos ao teste de preferência claro/escuro e de distribuição
vertical eliciada pela novidade. Todos os testes foram filmados e os vídeos foram
avaliados utilizando o X-PLO-RAT. Os dados foram expressos em média ± erro padrão.
Foi aplicado o teste de normalidade utilizando o teste Shapiro-Wilk e o teste
paramétrico ANOVA de uma via com pós-teste Tukey, considerando significativos
valores com p<0,05. Nós demonstramos que o
-tocoferol na dose de 1 mg/kg reverteu
todos os parâmetros do comportamento tipo ansiedade ampliado pela cafeína nos testes
de PCE e do DVN e esse efeito foi semelhante ao observado quando administrado um
inibidor da enzima óxido nítrico sintase (NOS), L-NAME. Portanto, o presente trabalho
demonstrou pela primeira vez que o efeito comportamental ampliado pela cafeína no
teste escotáxico e no DVN pode ser modulado pelo sistema nitrérgico e que o
-
tocoferol reverte esse efeito comportamental induzido pela cafeína de forma total.

Sistema de nanopartículas à base de lipídios têm sido usados como veículos experimentais para agentes quimioterápicos no tratamento do câncer. Recentemente essas preparações de nanopartículas foram testadas também em modelos animais de doenças inflamatórias cardiovasculares crônicas, doenças reumáticas entre outras. Acredita-se que esses sistemas suspostamente atenuem os graves efeitos tóxicos de agentes quimioterápicos antineoplásicos. Este estudo teve como objetivo investigar os efeitos da associação do paclitaxel a um sistema de nanopartículas à base de lipídios no tratamento crônico em primatas não-humanos, da espécie Cebus apella, por meio de extensas documentações e métodos detalhados da análise toxicológica através de bioquímica sérica, parâmetros hematológicos e histopatológicos. As nanopartículas a base de lipídios (LDE) eram constituída por ésteres de colesterol esterificado e colesterol, lectina e treolin, com adição de paclitaxel. Foram estudados dezoito Cebus apella; sendo que três animais foram tratados apenas com solução salina, administrada por via intravenosa, a cada três semanas, durante seis ciclos de tratamento; seis animais foram tratados com o paclitaxel associado a LDE no mesmo regime de administração, com três animais recebendo a dose mais baixa do fármaco (175 mg/m²) e três com a dose mais elevada (250mg/m2); seis animais foram tratados com o paclitaxel na forma comercial, sendo que três receberam as doses mais baixas (175 mg/m²) e outros três com doses mais elevadas (250mg/m2). Três semanas após o último ciclo de tratamento foram submetidos a eutanásia por dosagem letal de anestésico, e os fragmentos de tecidos foram recolhidos para a análise histopatológica. Em três animais não-tratados, a cinética plasmática da LDE foi determinada após a injeção intravenosa do colesterol radioativo (3H), seguido de coleta de sangue ao longo de 24 horas. O projeto foi aprovado pelo comitê de ética em pesquisa com animais de experimentação da UFPA (CEPAE/BIO008-11). No grupo LDE-paclitaxel, nenhuma toxicidade clínica foi observada, o peso, assim como o consumo de alimentos foram semelhantes aos animais pertencentes ao grupo controle. O tratamento foi interrompido após o segundo ciclo em quatro animais de grupo que recebeu o paclitaxel na forma comercial, devido a elevada toxicidade clínica, entretanto dois animais completaram os 6 ciclos de tratamento. Esses dois animais apresentaram perda de peso, náuseas e vômitos, diarréia, lesão inflamatória descamativa, perda de 70% do pelo corpóreo e diminuição da atividade física. A dose de paclitaxel 175 mg/m2 é usado em quimioterapia contra o câncer com uma toxicidade considerável, enquanto que a dose a 250 mg/m2 é intolerável e mostra toxicidade considerável nos pacientes. O uso de LDE como transportador de fármaco, em ambos as doses neutralizou consideravelmente a toxicidade do fármaco em primatas não humanos da espécie Cebus apella, intimamente relacionadas a sujeitos humanos. Isso foi observado não só devido as manifestações clínicas, bioquímicas e hematológicas, mas também pela análise histopatológica do estômago, intestino delgado e grosso, esôfago, pâncreas, traqueia e da vesícula biliar. Os resultados suportam a hipótese de que os sistemas de nanopartículas à base de lipídios utilizado como transportadores de droga pode oferecer ferramentas valiosas na diminuição da toxicidade e aumentar a segurança dos agentes quimioterápicos, assim como, amplia a sua utilização em outras doenças crônicas que não o câncer.

A tirosinase é uma enzima chave para a biossíntese de melanina. É uma enzima “cobre-dependente” que pode existir em três estados intermediários: desoxi (Cu1+-Cu1+), oxi (Cu2+-O2-Cu2+) e met (Cu2+-Cu2+). Apresenta atividade bifuncional, pois oxida fenóis ou catecóis em seus o-difenóis correspondentes, sendo que o processo de oxidação de fenóis pode ser descrito por cinética de Michaelis-Menten. Distúrbios na tirosinase estão associados com hiperpigmentação e escurecimento enzimático de frutas e fungos. Assim a busca por substâncias de origem natural ou sintética capazes de regular o comportamento desta enzima é fator chave para o tratamento de tais desordens. Nesta perspectiva, no presente trabalho buscou-se analisar bioquimicamente a atividade anti-tirosinase de análogos do ácido kójico derivados de 4H- pironas (S-01, S-02, S-03 e S-04) e derivados de diidropirano[3,2-b]cromenodionas (S-05, S-06, S-07 e S-08), quimicamente planejadas por modelagem molecular no LPDF, do ICEN da UFPA. A cinética das substâncias S-02, S-04, S-06, S-07 e S-08 apresentaram inibição do tipo competitiva, semelhante ao padrão de inibição do ácido kójico, com valores de Ki de 145,0 ± 20,0 μM; 64,0 ± 10,0 μM; 4,0 ± 0,0 μM; 6,0 ± 0,0 μM; 9,0 ± 0,0 μM, respectivamente, e de 5,0 ± 0,0 μM para o ácido kójico, enquanto a substância S-01 apresentou uma inibição do tipo mista (Ki = 999,0 ± 150,0 μM). Já as substâncias S-03 e S-05 não apresentaram atividade inibitória. As substâncias testadas demonstraram alto grau de segurança tanto na integridade de membrana de eritrócitos em teste de hemólise, quanto na viabilidade em teste com MTT em culturas de fibroblasto MRC5, em cultura de células nervosas de retina de embrião de galinha e em melanoma B16F10. Assim, demonstrou-se que as substâncias S-02, S-04, S-06, S-07 e S-08 apresentam atividade como potentes inibidores de tirosinase, podendo ser candidatos no tratamento de desordens de pigmentação.

As leishmanioses são protozoonoses causadas por parasitos do gênero Leishmania e estão distribuídas por diversas partes do mundo. Essa patologia se manifesta sobre diversas formas clínicas: Leishmaniose visceral (LV), Leishmaniose cutânea (LC) e Leishmaniose cutaneomucosa (LM). O parasito Leishmania apresenta duas formas evolutivas: a forma promastigota, de vida livre, e a forma amastigota, intracelular obrigatório, presente principalmente nas células fagocíticas mononucleadas. A inibição do crescimento ou destruição dos parasitos dentro da célula hospedeira é um mecanismo fundamental para erradicar a infecção. A inibição dos efeitos leishmanicidas do macrófago parece estar relacionada com a capacidade de algumas espécies em inibir a produção de óxido nítrico (NO). Estudos recentes têm mostrado que algumas espécies de Leishmania possuem a capacidade de produzir NO a partir de uma forma constitutiva da enzima Óxido Nítrico Sintase (cNOS). Este trabalho tem como objetivo detectar e localizar a enzima cNOS presente em promastigotas de Leishmania (Leishmania) amazonensis e Leishmania (Viannia) braziliensis. Para isto, o presente estudo utilizou citometria de fluxo, a qual permitiu quantificar a produção de NO nos parasitos, evidenciando a maior atividade da enzima cNOS em Leishmania (L.) amazonensis quando comparada com a espécie Leishmania (V.) braziliensis. Foi realizada a imunomarcação das formas promastigotas com o anticorpo anti-cNOS para observar a localização ultraestrutural da enzima por microscopia eletrônica de transmissão (MET), posteriormente a co-marcação com os anticorpos anti-cNOS e anti-GAPDH para confirmar a provável compartimentalização desta enzima em organelas glicossomais. Os resultados sugerem que a produção de NO por diferentes espécies de Leishmania é um processo localizado em organelas glicossomais com a captura do aminoácido L-arginina da célula hospedeira, o sequestro deste substrato priva o hospedeiro de sintetizar o NO exógeno danoso ao parasito. Esta modulação sugere mais um mecanismo de escape que os protozoár

Apesar dos esforços para sua eliminação como problema de saúde pública, a hanseníase permanece com alta prevalência em alguns países, como o Brasil, sendo o Estado do Pará responsável pelo diagnóstico de aproximadamente 10% dos cerca de 400.000 casos novos do Brasil nos últimos 10 anos. Até o momento, não existe nenhum teste de diagnóstico para detectar a hanseníase nos estágios iniciais, contribuindo assim para a manutenção das altas taxas de incidência da doença. Neste sentido, novos antígenos específicos do M. leprae que possibilitem o desenvolvimento de novos métodos de diagnóstico podem facilitar a detecção precoce de casos novos e contribuir para alcançar as metas de controle da hanseníase. Neste estudo, foi realizada avaliação clínica e dermatoneurológica dos participantes para a detecção de casos novos e foram coletadas amostras de sangue para pesquisa de anticorpos em dois momentos diferentes, T1 e T2, em um intervalo de tempo de 2 anos entre os mesmos. Os anticorpos IgM anti-ND-O-BSA e IgG anti-LID-1 foram detectados por ELISA, além de anti-IgM e anti-IgG associados para a pesquisa de anti-NDO-LID em amostras de plasma, também por ELISA ou sangue total pelo teste rápido OrangeLife® (OL) de 79 pessoas com hanseníase, 131 contatos e 331 estudantes do município de Breves, Estado do Pará. Nossos resultados mostraram alta incidência de hanseníase de 18,6% e 6,1% em contatos e estudantes respectivamente em T1 e de 19,8% e 9,4% em T2 e neste momento, entre contatos, foram positivos 44,3% para anti-ND-O-BSA, 7,86% para o anti-LID-1 e 37,4% para o anti-NDO-LID e para estudantes foram 49,5% para o anti-ND-O-BSA, 5,1% para o anti-LID-1 e 45% para o anti-NDO-LID. A associação entre os antígenos mostrou uma forte correlação para o ND-O-BSA e NDO-LID. A positividade para o OL em casos novos foi de 44,3% para MB, a maioria BT, em estudantes foi 47,4% e em contatos foi de 36,3%, com baixa concordância com ELISA anti-NDO-LID. No seguimento (T2), o percentual de casos novos foi de 35% e o maior percentual foi identificado entre indivíduos positivos para anti-ND-O-BSA. Os dados mostram alta incidência em contatos e estudantes através de busca ativa e seguimento sorológico, e concluímos que o antígeno ND-O-BSA se mostrou mais sensível no ensaio de ELISA para a identificação de casos novos em populações endêmicas.

A camada I tem como característica principal a baixa quantidade de neurônios e uma alta densidade de fibras nervosas. A morfologia dos neurônios da camada I ainda é pouco estudada, tanto que nos estudos que avaliaram a morfologia desses neurônios não se chegou ainda a um consenso sobre as formas e funções desses neurônios. Este estudo avaliou a morfologia dos neurônios da camada I do córtex visual de duas espécies de roedores: Cavia porcellus, popularmente conhecido no Brasil como porquinho-da-índia e Rattus norvegicus, que é o rato e foi utilizada a linhagem Wistar, comumente usado nas pesquisas científicas. O porquinho-da-índia é um modelo animal muito estudado, utilizado em diversos segmentos da ciência. Apesar dessa espécie ser bem estudada, trabalhos na camada I desse animal são relativamente raros, especialmente em relação à morfologia e eletrofisiologia dos neurônios dessa região cortical. Pesquisas em ratos sobre os neurônios da camada I são mais frequentes, tanto em relação a morfologia quanto a eletrofisiologia. Para discriminar as possibilidades de diferenças na morfologia dos neurônios da camada I do córtex visual do porquinho-da-índia e do rato, este estudo classificou esses neurônios de acordo com a trajetória de seus dendritos e analisou as medidas dendríticas utilizando a técnica de injeção intracelular de biocitina. Após a classificação dos neurônios as comparações foram feitas entre os mesmos tipos celulares de cada roedor. Foram utilizados 35 porquinhos-da-índia da variedade Dunkin-Hartley de pêlo curto de ambos os sexos com idades de 4 a 5 dias de vida pós-natal. Quanto aos ratos, foram utilizados 30 ratos da variedade Wistar, de ambos os sexos com idades de 14 a 21 dias de vida pós-natal. Os animais foram anestesiados e tiveram seus encéfalos removidos, hemisférios separados e foram realizados cortes no plano coronal na região occipital onde se localiza a área visual dos roedores. As fatias foram mantidas em líquido cérebro-espinhal artificial e em seguida levadas ao microscópio para injeção de biocitina e posteriormente foram fixadas e tratadas para montagem em lâmina e contracoradas com Nissl para melhor visualização. Os neurônios encontrados foram classificados como: horizontais, ascendentes, descendentes e radias. Foram analisadas as seguintes medidas dendríticas: área do campo receptor, comprimento dendrítico total e médio, área total do corpo celular, número de dendritos, distância da pia-máter e análise da distribuição de Sholl. Dos resultados obtidos os mais notáveis foram o alcance dos ramos dendríticos e o tamanho do corpo celular dos neurônios da camada I do porquinho-da-índia quando comparados aos do rato. Isso sugere que, nessa espécie, um maior número de microcircuitos neurais podem ser estabelecidos, e por conseguinte maior taxa metabólica, justificada pelo maior tamanho do corpo celular.

O acidente vascular cerebral isquêmico (AVCi) causa danos celulares por provocar intensa excitotoxicidade e estresse oxidativo após privação de oxigênio e glicose para uma região do encéfalo. Neste trabalho, investigamos o potencial neuroprotetor da planta amazônica Brosimum acutifolium que é rica em flavanas como a 4',7-diidroxi-8-(3,3-dimetilalil)flavana (brosimina b, aqui abreviada como Bb) que apresenta elevado potencial antioxidante. Utilizamos cultura de células retinianas de embrião de galinha submetidas a hipóxia experimental, por privação de oxigênio e glicose, para avaliarmos o potencial antioxidante da Bb através da análise do sequestro do radical 2,2-difenil-1-picril-hidrazil (DPPH). Além disso, avaliamos a viabilidade celular (VC) e o perfil oxidativo e antioxidativo após 3, 6 e 24 horas de hipóxia, pela produção de oxigênio reativo (O2-) e atividade antioxidante endógena pela enzima catalase, respectivamente. Nossos resultados demonstram que nosso modelo experimental de hipóxia in vitro provoca redução tempo-dependente da VC, acompanhada por intenso estrese oxidativo, devido à excessiva produção de oxigênio reativo (O2-). O tratamento com Bb (10μM) protegeu significativamente a viabilidade celular durante 3 e 6 h de hipóxia experimental em células retiniana cultivadas in vitro, além de favorecer o aumento da atividade da enzima catalase em todos os tempos testados. Desta forma, concluímos que a Bb possui ação antioxidante e neuroprotetor por contribuir na defesa contra o estresse oxidativo induzido em condições de hipóxia, tornando-se como uma droga com potencial uso em tratamentos em casos de AVCi in vivo.

O acidente vascular cerebral (AVC) é a maior causa de mortes e incapacidades neurológicas no Brasil, e mais de 80% deles são decorrentes de evento isquêmico. Os sobreviventes de AVC apresentam uma variedade de déficits motores, cognitivos e sensoriais, que prejudicam suas atividades de vida diária, limitando assim sua independência. Portanto, torna-se cada vez mais necessário elaborar estratégias terapêuticas que promovam a recuperação funcional de pacientes acometidos por AVC. Após isquemia do tecido nervoso, ocorre no meio extracelular a super expressão de moléculas inibitórias a regeneração neuronal e à plasticidade sináptica, como os proteoglicanos de sulfato de condroitina (PGSCs), o principal componente das redes perineuronais (RPNs). A remoção destas moléculas com a ação da enzima condroitinase ABC (ChABC) tem sido usada como estratégia para induzir a plasticidade neuronal. Outro fator que tem sido utilizado para estimular a neuroplasticidade é o exercício físico específico para o membro afetado após AVC. O exercício físico está relacionado à liberação de neurotrofinas, importantes para a regeneração do sistema nervoso. Portanto, a remoção dos PGSCs junto com o exercício físico pode potencializar a indução da plasticidade cerebral e recuperação funcional após lesão isquêmica experimental na área sensório-motora de ratos. Para testar nossa hipótese, utilizamos n=16 ratos (Ratus norvergicus) da linhagem Wistar, divididos nos seguintes grupos experimentais (todos com sobrevida de 21 dias após AVC isquêmico): Grupo Controle ou BSA (Isquemia experimental, implante de Elvax saturado com BSA); Grupo Exercício (Isquemia experimental, implante de Elvax saturado com BSA + exercício físico específico); Grupo ChABC (Isquemia experimental, implante de Elvax saturado com ChABC); e Grupo ChABC + Exercício (Isquemia experimental, implante de Elvax saturado com ChABC + exercício físico específico). A lesão isquêmica foi induzida através de microinjeções do vasoconstritor Endotelina-1 (ET-1) no córtex sensório-motor, na representação da pata anterior. Logo em seguida foi implantado uma microfatia de polímero de Etileno vinil acetato saturado com ChABC (grupos ChABC e ChABC + Exercício) ou BSA (grupos Controle e Exercício). Foram avaliadas a área de lesão e a degradação dos PGSCs, além da recuperação funcional da pata afetada através do teste da exploração vertical e do teste da escada horizontal. Avaliamos a área de lesão (mm2) com auxílio do programa ImageJ (NIH, USA), delimitando a área com palor celular e também marcada com azul de colanil que estava presente na solução de injeção do peptídeo vasoconstritor ET-1 e verificamos que não houve diferença significativa no tamanho da área de lesão entre os grupos Controle (0,48±0,12), Exercício (0,46±0,05), ChABC (0,50±0,18) e ChABC + Exercício (0,55±0,05) (ANOVA, pós-teste de Tukey, ***p<0,001; **<0,01; *p<0,5). Animais que foram submetidos à remoção enzimática dos PGSCs apresentaram imunomarcação para o anticorpo anti-condroitin-4-sulfato (C4S) na área de lesão ao final da sobrevida, não havendo
evidencias de degradação de PGSCs nos grupos Controle e Exercício. Verificamos ainda no teste do cilindro que a indução da lesão isquêmica não provocou perda funcional ampla, não alterando o comportamento exploratório, nem a frequência de uso da pata anterior afetada dos animais após a lesão (grupo Controle: pré-lesão ou baseline (0,33±0,10), 3 (0,29±0,17), 7 (0,30±0,10), 14 (0,29±0,16) e 21 (0,27±0,13) dias após a lesão; grupo Exercício: pré-lesão ou baseline (0,30±0,12), 3 (0,32±0,24), 7 (0,19±0,37), 14 (0,31±0,10) e 21 (0,32±0,09) dias após a lesão; grupo ChABC: pré-lesão ou baseline (0,34±0,07), 3 (0,20±0,11), 7 (0,23±0,07), 14 (0,33±0,14) e 21 (0,39±0,16) dias após a lesão; grupo ChABC + Exercício: pré-lesão ou baseline (0,34±0,04), 3 (0,20±0,09), 7 (0,26±0,04), 14 (0,18±0,08) e 21 (0,27±0,04) dias após a lesão) (ANOVA, pós-teste de Tukey, ***p<0,001; **<0,01; *p<0,5). O grupo que teve apenas a remoção dos PGSCs apresentou um melhor desempenho motor no teste da escada horizontal, mantendo sua frequência de acertos quando comparado aos demais grupos, sendo que ao final da sobrevida de 21 dias, os grupos Controle e ChABC + Exercício alcançaram uma recuperação espontânea (equivalente ao teste pré-lesão), se aproximando do grupo ChABC. Apenas o grupo tratado somente com Exercício não alcançou a recuperação espontânea, apresentando um desempenho motor significativamente inferior aos demais grupos em todos os momentos de reavaliação (grupo Controle: pré-lesão ou baseline (7,70±0,54), 3 (5,30±0,71), 7 (5,4±1,14), 14 (5,20±0,37) e 21 (6,70±0,48) dias após a lesão; grupo Exercício: pré-lesão ou baseline (8,40±0,28), 3 (4,30±0,48), 7 (4,75±0,50), 14 (5,35±0,41) e 21 (5,05±0,67) dias após a lesão; grupo ChABC: pré-lesão ou baseline (7,65±0,97), 3 (6,90±0,65), 7 (7,80±0,37), 14 (7,15±0,87) e 21 (7,45±0,32) dias após a lesão; e grupo ChABC + Exercício: pré-lesão ou baseline (8,10±0,22), 3 (3,65±1,48), 7 (4,95±1,06), 14 (7,35±0,37) e 21 (6,70±0,48) dias após a lesão (ANOVA, pós-teste de Tukey, ***p<0,001; **<0,01; *p<0,5). Portanto, a remoção dos PGSCs, o exercício físico forçado precoce e sua associação não influenciaram no tamanho da área de lesão após isquemia focal no córtex sensório-motor. Porém, apenas a remoção dos PGSCs das redes perineuronais melhorou precocemente o desempenho motor do membro afetado após isquemia focal no córtex sensório-motor. Enquanto que a remoção dos PGSCs associada ao exercício físico melhorou o desempenho motor do membro afetado após a lesão, porém essa melhora foi tardia. E o exercício físico aplicado precocemente após isquemia focal no córtex sensório-motor prejudicou o desempenho motor do membro afetado.

A Síndrome da Imuno Deficiência Adquirida (SIDA) é uma enfermidade que assola a população mundial há décadas e ouvir esse diagnóstico era como uma “sentença de morte”. Com o advento da novas terapêuticas medicamentosas, a característica aguda da doença passou a ser de caráter crônico. Todavia, as drogas utilizadas na Terapia Antiretroviral (TARV) apresentam reações adversas, especialmente quando o paciente é submetido a longo prazo de utilização do chamado “coquetel”. Uma das reações adversas da TARV é a Lipodistrofia, que em escala molecular ocasiona a apoptose de adpócitos e alterações mitocondriais nas fibras musculares. Sendo assim, o objetivo deste trabalho foi de investigar as repercussões musculares da Lipodistrofia e a alteração dos padrões de marcha e equilíbrio de pacientes nesse quadro clínico. Foram avaliados 38 sujeitos de ambos os sexos, divididos em dois grupos: HIV positivo com Lipodistrofia (HIVL) e HIV positivo sem Lipodistrofia (HIV). No teste de Equilíbrio foi utilizada uma Plataforma de força (EMGSystem do Brasil), que avalia o deslocamento do Centro de pressão (Cop) nos sentidos anteroposterior (AP) e mediolateral (ML) do indivíduo gerando as variáveis deslocamento linear total, área total de deslocamento, velocidade de deslocamento e amplitude do deslocamento, num período de sessenta segundos para cada coleta. Para o teste de Marcha foi utilizado o Eletromiógrafo de 8 canais (EMGSystem do Brasil) para captar o sinal elétrico dos músculos Reto Femoral (RF), Bíceps Femoral (BF), Gastrocnêmio Lateral (GL), Tibial Anterior (TA) e Glúteo Médio (GMd) durante a deambulação e o processamento do sinal eletromiográfico foi feito através do modelo matemático Root Mean Square (RMS) e normalizado pela contração voluntária máxima (CVM). Os resultados de cada grupo foram expressos em média e desvio padrão e comparados através do Teste t de Student para amostras paramétricas e o teste Mann-Whitney para amostras não-paramétricas. As análises dos resultados nas duas fases do ciclo da marcha mostraram diferenças significativas. Na fase de Apoio e na fase de Balanço os sinais eletromiográficos do músculo GMd e TA foram maiores no grupo HIVL em relação ao grupo HIV. Quanto ao equilíbrio as variáveis com significância estatística na comparação dos grupos foram o Deslocamento total e a Área do deslocamento, ambas maiores no grupo HIVL em relação ao grupo HIV. Com isso concluímos que os pacientes com a Síndrome Lipodistrófica apresentaram alteração dos padrões de marcha e equilíbrio.

Neuroblastoma é a neoplasia mais frequentemente diagnosticada na infância.
O termo é comumente usado para se referir a uma ampla variedade de
tumores neuroblásticos, incluindo os neuroblastomas, ganglioneuroblastomas e
ganglioneuromas. Estimativas mostram que 8 milhões de crianças até 15 anos
de idade por ano são atingidas por esta neoplasia, onde 80% dos casos são
acometidos em até 4 anos de idade, o tumor é derivado de células malignas
embrionárias advindas de células neuronais primordiais, desde gânglios
simpáticos até medula adrenal e outros pontos. Neste estudo, foi avaliado o
potencial citotóxico do composto 4,2´,3´,4´ tetrametoxi chalcona em modelo in
vitro de neuroblastoma B103 de rato. Foram preparadas soluções estoques da
droga a 50mM em dimetilsulfóxido (DMSO) e armazenadas a -20ºC para o
preparo de novas concentrações (150μM, 100 μM, 75 μM e 50 μM). A
viabilidade celular foi testada a partir de cultura de células da glia do córtex de
rato e de neuroblastoma b103. Ensaios de migração celular e formação de
colônias também foram realizados. Para a análise estatística foi realizado a
análise de variância um critério (ANOVA) seguido pelo teste de Tukey,
utilizando-se o programa BioEstat 5.0. Na avaliação do efeito citotóxico das
chalconas, foi observado que o tratamento com o composto 4,2`3`4´-
tetrametoxi chalcona não demonstrou nenhum efeito citotóxico contra células
normais do córtex de rato para as concentrações testadas, enquanto que em
culturas de células de neuroblastoma B103 foi demonstrado que esta droga
promove a morte celular de forma significativa.

Os meningiomas constituem o segundo tipo de tumor primários cerebral mais comum,
originando-se nas meninges que revestem o cérebro e a medula espinhal. Possuem
crescimento lento, sendo encontrados com maior freqüência no SNC. Na maioria dos
casos são benignos, porém há também casos de meningiomas classificados como
malignos. No nível citogenético, os meningiomas são os tumores mais bem estudados
em humanos, e os resultados demonstraram que as alterações mais frequentes nesse tipo
de tumor tem sido a perda de uma cópia do cromossomo 22 e a deleção do braço curto
do cromossomo 1. Essas alterações têm sido associadas ao processo de gênese tumoral,
por serem características de tumores de baixo grau, principalmente deleções envolvendo
o cromossomo 22. Dessa forma, o objetivo do presente trabalho foi analisar a
recorrência de alterações no número de cópias (CNAs) envolvendo os cromossomos 1p
e 22 em meningiomas de grau I e II, além de averiguar a existência de outros rearranjos
recorrentes, por meio da análise genômica comparativa de alta resolução (array-CGH).
As amostras analisadas foram provenientes de oito pacientes. Todas as amostras
apresentaram ganhos e perdas de diversos segmentos cromossômicos. Com exceção de
um caso, todos os outros apresentaram em maior ou menor grau mais deleções do que
amplificações. A perda de segmentos localizados em 1p foi observada em todas as
amostras analisadas. Algumas CNAs apresentaram recorrência em até seis dos oito
casos. O cromossomo 22 apresentou CNAs em todas as amostras, mas a monossomia
total só foi observada em duas das oito amostras. A análise global de CNAs em todas as
amostras demonstrou que, apesar de alterações em 1p e 22 serem as modificações mais
observadas, como o esperado, outras regiões genômicas também se apresentaram
modificadas em várias amostras, apontando para um possível envolvimento dessas
modificações com o processo de tumorigênese e progressão tumoral. Algumas delas,
como alterações nos pares 9, 12 e 17, já foram observadas em outros trabalhos e foram
correlacionadas com meningiomas atípicos e anaplásicos. Dessa forma, os dados
obtidos apontam para a existência de um número maior de alterações genômicas em
meningiomas de baixo grau, refutando, em parte, a afirmação de que esses tumores são
caracterizados por um pequeno número de alterações quando comparados com tumores
de malignidade maior. No entanto, o fato desses tumores apresentarem as alterações que
são clássicas dos meningiomas, mesmo os benignos, como as deleções em 1p e em 22q,
pode ser um indício de que estas alterações devem estar ligadas com os eventos iniciais
destes meningiomas, como já foi sugerido diversas vezes por outros autores.
Concluindo, essas alterações permanecem como marcadores importantes em
meningiomas, e as relações dessas e outras CNAs com a resposta a diferentes
tratamentos e ocorrência de recidivas devem ser o próximo passo após a caracterização
citogenômica baseada em array-CGH.

Este trabalho investiga as alterações neuropatológicas e do comportamento em

tarefas hipocampo-dependentesinduzidas pela encefalite experimental aguda associada

ao vírus Piry. Três janelas temporais (3, 7 e 10 dias após a inoculação) foram avaliadas

e dois ambientes testados de forma a avaliar se o enriquecimento ambiental é influencia

as alterações associadas à infecção. Camundongos fêmeas de dois meses de idade foram

mantidos em ambientes empobrecido (IE) ou enriquecido (EE) durante seis meses e

foram testados para as atividades de burrowing, de campo aberto e de discriminação

olfatória. Após esse período os animais foram inoculados por via intranasal com 5μlde

homogenado de cérebro normal (NBH) ou homogenado de cérebro infectado pelo vírus

Piry (PY) e então reorganizados nos seguintes grupos: IENBH, IEPY, EENBH e EEPY,

com cinco animais cada. Três, sete e dez dias após a inoculação (dpi), os animais de

cada janela temporal foram perfundidos com fixador aldeídico. Os encéfalos foram

removidos, seccionados e as secções foram processadas para imunohistoquímica para

anti-Piry e para anti-Iba-1 para marcação dos antígenos virais e de

macrófagos/micróglias, respectivamente. Quantificações estereológicas foram feitas em

cada camada celular de CA3 usando o método do fracionador óptico.Estimativas do

fracionador óptico mostraram que não houve alteração da estimativa do número total de

micróglias em CA3 nos grupos analisados, indicando que a infecção não alterou o

número de células, mas a morfologiadas micróglias, que se mostraram mais ativadas no

grupo IEPY do que no grupo EEPY. Os resultados revelaram a presença de antígenos

virais no bulbo olfatório, córtex piriforme, estriado e fimbria, ao longo da via olfatória.

A atividade de burrowing no grupo IEPY diminuiu na primeira janela temporal e

permaneceu baixa até a última janela, enquanto que no grupo EEPY não houve

alteração neste teste. Na atividade de campo aberto, o grupo IEPY aumentou o tempo

imóvel já na primeira janela e continuou aumentando até a última; reduziu o número de

linhas cruzadas na segunda janela e permaneceu reduzindo na última; e diminuiu o

tempo na zona central na segunda e última janela. Já o grupo EEPY, aumentou o tempo

imóvel e reduziu o número de linhas cruzadas na segunda janela. No teste de

discriminação olfatória, o principal grupo afetado foi o grupo IEPY, que não

discriminou os dois odores na última janela, enquanto que o grupo EEPY não teve

alteração na discriminação.

O Método CANOVA homeopática. CA é indicado em condições clínicas nas quais o sistema imune se

encontre comprometido. O N-Metil-N-Nitrosoureia (NMU) é um agente N-nitroso alquilante

e carcinogênico utilizado como modelo experimental em roedores e macacos. O NMU

também apresenta efeitos genotóxicos/mutagênicos analisáveis por testes clássicos de

detecção de danos ao DNA e aberrações cromossômicas. Apesar de vários estudos

terem demonstrado resultados promissores na utilização do medicamento CA, não

existem trabalhos relatando possíveis efeitos antigenotóxicos deste medicamento, a

despeito de seu potencial anticarcinogênico. Assim, o presente trabalho avaliou

efeitos antigenotóxicos e anticitotóxicos do medicamento CA em linfócitos humanos

expostos ao NMU. Foram utilizadas amostras de linfócitos humanos que foram

submetidos a diferentes concentrações de uma mistura contendo CA e NMU. A

viabilidade das células expostas ao NMU foi avaliada pelo ensaio MTT, a

genotoxicidade/antigenotoxicidade do CA foi avaliada pelo teste do cometa e a

anticitotoxicidade do CA foi verificada pela quantificação de apoptose e necrose utilizando

corantes fluorescentes (laranja de acridina/brometo de etídeo). No teste MTT verificamos

que o NMU conseguiu diminuir a viabilidade dos linfócitos de forma significativa. No teste

do cometa foi observado que CA diminui significativamente os danos ao DNA induzidos

pelo NMU, caracterizando um claro efeito antigenotóxico do composto homeopático. CA

também diminuiu de forma significativa a freqüência de apoptose induzida pelo NMU em

leitura realizada após 24 horas de tratamento. Concluímos que o CA apresentou um efeito

antigenotóxico e anticitotóxico nas condições avaliadas no presente estudo,

demonstrando, assim, um claro potencial citoprotetor.

O Acidente vascular encefálico (AVE) é considerado uma das mais importantes causas de morte no mundo. Poucas condições neurológicas são tão complexas e devastadoras, provocando em seus sobreviventes, déficits neurológicos incapacitantes ou até mesmo a morte. As regiões corticais são comumente afetadas por AVE, o que resulta em perda sensorial e motora. O estabelecimento dos padrões neuropatológicos em regiões corticais, incluindo a área somestésica, é fundamental para a investigação de possíveis intervenções terapêuticas. No presente estudo, investigamos os padrões de perda neuronal, microgliose, astrocitose, neurogênese, e os déficits funcionais no córtex somestésico primário de ratos adultos, submetidos a lesões isquêmicas focais, induzidas através de microinjeções de 40 pmoles de endotelina-1 (ET-1). Foram utilizados 30 ratos (Rattus Norvegicus) da linhagem Wistar, adultos-jovens, pesando em torno de 250-280g. Os animais divididos em 3 grupos de (10), de acordo com o tempo de sobrevida 1 dia, 3 dias e 7 dias. Os animais foram anestesiados com injeção intraperitoneal, de uma mistura de cloridrato de Cetamina (72mg/kg) e Xilazima (9mg/kg), submetidos a cirurgia após os tempos de sobrevida, foram perfundidos. Os animais do grupo de (7dias), um dia antes e sete dias após a cirurgia passaram por uma avaliação, através de testes comportamentais (Escala Neurológica de Bederson, Teste da Colocação da Pata Anterior e Teste do Canto). Analises qualitativa e quantitativa foram realizadas na área somestésica primária. Secções de 50µm foram coradas pela técnica de violeta de cresila, secções de 40 µm foram reagidas pela histoquímica da citocromo oxidase para marcação do campo de barris e secções de 20µm foram marcadas por imunohistoquímicas, para neurônios (anti-NeuN), microglia ativada e não ativada (IBA-1), macrófagos/microglia (ED-1), astrócitos (GFAP) e neuroblastos (DCX). As comparações estatísticas entre os grupos foram feitas por análise de variância (ANOVA), um critério de correção a posteriore de Tukey, considerando-se como nível de significância de 95% e nível de confiança de (p< 0,05). Todas as análises estatísticas foram realizadas utilizando o programa de computação Bioestat (5.0), o programa Graphpad (Prism 5.0) e o programa Microsoft Office Excel . Os resultados foram os seguintes: A Escala Neurológica de Bederson indicou a gravidade do déficit entre os grupos controles e isquêmicos. O teste de Colocação da Pata Anterior evidenciou a assimetria na resposta entre as patas (afetadas e não afetadas). O Teste do Canto demonstrou assimetria de retorno pelos lados esquerdo e direito, de acordo com os testes. Microinjeções de ET-1 induziram lesão isquêmica focal na área somestésica primária com perda neuronal (NeuN+), significante nos tempos de (3 e 7 dias) após a lesão. Ativação microglial progressiva (ED1+) e (IBA1+) nos tempos de (1, 3 e 7 dias) depois da lesão, ativação progressiva de astrócitos (GFAP+) nos tempos de (1, 3, e 7 dias) após a lesão e presença de  neuroblastos (DCX+), na zona subventricular significantes nos tempos de (3 e 7 dias) . Não houve migração de neuroblastos (DCX+), significativos para o córtex somestésico primário

Estudou-se possíveis efeitos da estimulação multisensorial e cognitiva sobre o declínio

cognitivo senil agravado pelo ambiente empobrecido das instituições de longa permanência.

Para isso, dois grupos de estudo foram formados: 1) institucionalizados, aqueles que habitam

em instituições de longa permanência e 2) não institucionalizados, que habitam em

comunidade com seus familiares. Os grupos foram avaliados e submetidos ao programa de

intervenção multisensorial e cognitiva. As avaliações eram compostas pelo MEEM e testes

específicos de linguagem e foram realizadas em três momentos diferentes: avaliação inicial

(antes do início da intervenção); reavaliação intermediária (três meses de intervenção – após

24 oficinas) e reavaliação final (seis meses totais de intervenção – após 48 oficinas).

Comparando os grupos na avaliação inicial, o grupo institucionalizado mostrou-se com

menores pontuações nos testes aplicados. Os grupos apresentaram melhores desempenhos

após o programa de intervenção multisensorial e cognitiva, com ênfase na evolução do grupo

institucionalizado.

A atrofia é uma resposta imediata do músculo em situações de tensão e carga reduzida e caracteriza-se por mudanças morfológicas, aumento da proteólise muscular, perda de massa e redução da área da fibra que estão implicadas em déficits funcionais, afetando assim a qualidade de vida dos indivíduos. Rupturas tendíneas ocasionam atrofia muscular devido à intrínseca relação funcional existente entre ambas as estruturas, músculos-tendões. Considerando a injúria tendínea, trabalho prévio do nosso grupo identificou que a inibição da síntese de óxido nítrico localmente a injúria acelerou a recuperação histológica no tendão e a melhora funcional em animais tenotomizados. Desta forma, a proposta do trabalho é avaliar os efeitos da inibição nitrérgica local no tendão em relação ao padrão de regeneração muscular. Portanto, para gerar atrofia muscular esquelética, o trabalho utiliza o modelo experimental de ruptura do tendão calcâneo com posterior sutura. Os grupos foram divididos em controle, ruptura, ruptura+veículo (Salina 0,9%) e ruptura+L-nitro-arginina-metil-éster (L-NAME, 5mM). As amostras foram coletadas 14 e 21 dias seguintes ao procedimento cirúrgico experimental. Objetivando avaliar a dosagem de proteínas, o método de Bradford foi utilizado. As amostras também foram reservadas para processamento histológico qualitativo e quantitativo da área da fibra muscular e presença de lesões de núcleo central. Assim como no trabalho prévio de nosso grupo, acreditamos que a ação da droga restringiu-se ao local, pois não ocasionou fortes influências em relação ao peso corporal dos animais, que foi medido nos dias 0, 7, 14 e 21. O grupo tratado com L-NAME apresentou diminuição significativa no número de lesões de núcleo central no 14º dia pós-operatório e aumento nos níveis de proteína e área da fibra no 21º dia. Em conjunto, nossos resultados sugerem que houve efeito benéfico da inibição local da NOS após a ruptura com relação à atenuação da atrofia, contribuindo para acelerar a regeneração muscular.

A sobrevida da população tem aumentado de forma progressiva e atribui-se à melhoria da qualidade dos serviços de saúde e das condições gerais de vida, sendo marcante sobretudo nos países industrializados. Este aumento da expectativa de vida repercute no aumento da incidência de doenças comuns em idades avançadas. O envelhecimento é considerado fator de risco para o desenvolvimento de doenças neurodegenerativas como a doença de Alzheimer (DA). Uma das teorias para a patogênese da DA postula que a neurodegeneração é o resultado de alterações no metabolismo oxidativo com acometimento do tecido cerebral vulnerável. O fato de o envelhecimento ser um fator de risco na DA, reforça também a hipótese da participação dos radicais livres, pois os efeitos de sua ação podem se acumular durante anos. A DA é uma doença insidiosa e progressiva e caracteriza-se clinicamente por uma perda progressiva da memória e de outras funções cognitivas, além de mudanças comportamentais e sociais. O déficit de memória é o principal e usualmente o primeiro sintoma da DA, com comprometimento especialmente da retenção e recordação de novas informações. O presente trabalho visa avaliar se ocorrem alterações no metabolismo oxidativo detectáveis no sangue de pacientes com a DA, e se estas podem ser relacionadas com os diferentes estágios da doença e com o quadro cognitivo dos pacientes. Foram avaliados 30 pacientes com a doença de Alzheimer e 28 indivíduos no grupo controle atendidos na Unidade de Ensino e Assistência de Fisioterapia e Terapia Ocupacional da Universidade do Estado do Pará (UEAFTO-UEPA). O metabolismo oxidativo foi avaliado através da medida da capacidade antioxidante total equivalente ao Trolox (TEAC) e da mensuração dos níveis das substâncias que reagem ao ácido tiobarbitúrico - TBARS. Também foram realizados testes neuropsicológicos em todos os sujeitos participantes do estudo. Observou-se que a capacidade antioxidante total estava significativamente diminuída nos pacientes com a DA em comparação com o grupo controle independentemente do estágio da doença, porém não houve diferença significativa entre as diferentes fases da DA. Na avaliação de TBARS houve uma tendência para maiores concentrações nos pacientes com DA do que no grupo controle, porém a diferença não foi estatisticamente significativa, apenas a fase moderada foi significativa quando comparada com o grupo controle. Não foram observadas correlações significativas no desempenho dos testes neuropsicológicos com os níveis de TBARS e TEAC nos pacientes com a DA.

O ácido γ-aminobutírico (GABA) e o glutamato são os principais neurotransmissores inibitório e excitatório no Sistema Nervoso Central (SNC) e são fundamentais para o processamento visual. Estudos revelam que o glutamato induz liberação de GABA na retina, mas os mecanismos envolvidos nesta liberação não são bem elucidados. Trabalhos prévios também apontam que compostos tióis regulam a liberação de GABA no hipocampo, mas ainda não são esclarecidos os efeitos de tióis (-SH) sobre os níveis endógenos deste neurotransmissor na retina. Neste intermédio, a glutationa (GSH) além de ser o mais importante dos compostos tióis, vem demonstrando exercer um papel neuromodulador na liberação de neurotransmissores. Desta forma, o objetivo deste trabalho foi avaliar um possível efeito modulador de GSH sobre a liberação de GABA mediada por glutamato em retinas de embrião de galinha. Para isso, utilizamos como modelo experimental tecido retiniano íntegro de embrião de galinha, com sete ou oito dias de desenvolvimento. Nos ensaios de liberação de GABA, as retinas foram tratadas com GSH (100 e 500 μM); glutamato (50 e 500 μM) e Butionina Sulfoximina (BSO), inibidor da síntese de glutationa, (50 μM) por 15 minutos, e os níveis de GABA liberado para o meio extracelular foram quantificados por Cromatografia Líquida de Alta Eficácia (CLAE). Para experimentos de liberação de compostos tióis (–SH), as retinas foram incubadas com glutamato (100 μM) com ou sem Na

+ por 15 minutos, e os seus níveis extracelulares foram determinados pela reação com DTNB e quantificados por espectrofotometria. Os resultados revelam que o glutamato e GSH liberam GABA. Nossos dados também demonstram que BSO atenua a liberação de GABA promovida por glutamato. Além disso, demonstramos que glutamato induz liberação de compostos tióis independentemente de sódio. Sendo assim, sabe-se que glutamato libera tióis, dentre estes se têm GSH como o mais proeminente, libera também GABA e que GSH é capaz de aumentar os níveis extracelulares de GABA, de forma que uma vez inibida a síntese de GSH por BSO, a liberação de GABA por glutamato é atenuada; então se sugere uma possível modulação de GSH na liberação de GABA induzida por glutamato em retinas íntegras de embrião de galinha.

A resposta inflamatória pode exacerbar o processo lesivo após desordens neurais agudas. O dimorfismo sexual gerado pelas diferentes presenças hormonais existentes entre macho e fêmea tem demonstrado habilidades neuroprotetoras endógenas opostas, apresentando a uma melhor preservação da integridade do tecido nervoso na fêmea, putativamente devido à presença dos hormônios ginógenos. No entanto, não existem investigações comparando como essa diferença pode afetar a resposta inflamatória durante o AVE. No presente estudo, investigaram-se as diferenças nos processos inflamatórios agudos do dimorfismo sexual de ratos adultos de ambos os sexos submetidos à lesão isquêmica aguda induzida por Endotelina (ET1) no corpo estriado. Seis grupos experimentais foram delineados: Animais machos de 24 horas de sobrevida (n= 8); machos de 72 horas de sobrevida de (n=8); machos de 7 dias de sobrevida (n=8); e fêmeas de 24 horas de sobrevida (n= 8); fêmeas de 72 horas de sobrevida de(n=8); fêmeas de 7 dias de sobrevida. A análise histopatológica geral foi realizada em secções coradas pela violeta de cresila. Macrófagos, astrócitos e neurônios foram identificados por imuno-histoquímica com anticorpos específicos para estas células inflamatórias (ED1, anti-GFAP e Anti-NeuN, respectivamente). Realizou-se contagem de micróglia/macrófagos ativados e corpos neuronais nos grupos experimentais mencionados. Não se notou diferença quantitativa entre os diferentes sexos, contudo houve uma aparente queda na quantidade de macrófagos/micróglia em 3 dias porém tanto para os machos quanto para as fêmeas. Apresentando aparentemente alguma diferença na ativação astrocitária sendo mais forte em machos. Os resultados sugerem que as diferenças sexuais, pelo menos na linhagem Lister hooded, não é suficiente para causar diferenças significativas na preservação do tecido nervoso e em alguns aspectos da resposta inflamatória após a indução de isquemia cerebral por meio de ET1.

A pimenteira-do-reino (

Piper nigrum L.) constitui uma das espécies de pimenta mais amplamente utilizadas no mundo, pertencendo à família Piperaceae, a qual compreende cerca de 1400 espécies distribuídas principalmente no continente americano e sudeste da Ásia, onde esta cultura originou. A pimenteira-do-reino foi introduzida no Brasil no século XVII, e tornou-se uma cultura de importância econômica desde 1933. O Estado do Pará é o principal produto brasileiro de pimenta-do-reino, contudo sua produção vem sendo afetada pela doença fusariose causada pelo fungo Fusarium solani f. sp. piperis. Estudos prévios revelaram a identificação de sequencias de cDNA diferencialmente expressas durante a interação da pimenteira-do-reino com o F. solani f. sp. piperis. Entre elas, uma sequencia de cDNA parcial que codifica para uma proteína transportadora de lipídeos (LTP), a qual é conhecida por seu importante papel na defesa de plantas contra patógenos e insetos. Desta forma, o objetivo principal deste trabalho foi isolar e caracterizar as sequencias de cDNA e genômica de uma LTP de pimenteira-do-reino, denominada PnLTP. O cDNA completo da PnLTP isolado por meio de experimentos de RACE apresentou 621 bp com 32 pb and 235 bp nas regiões não traduzidas 5‘ e 3‘, respectivamente. Este cDNA contem uma ORF de 354 bp codificando uma proteína deduzida de 117 resíduos de aminoácidos que apresentou alta identidade com LTPs de outras espécies vegetais. Análises das sequencias revelou que a PnLTP contem um potencial peptídeo sinal na extremidade amino-terminal e oito resíduos de cisteína preditos por formar quatro pontes de dissulfeto, as quais poderiam contribuir para a estabilidade desta proteína. O alinhamento entre as sequencias de cDNA e genômica revelou a ausência de introns na região codificante do gene PnLTP, o que está de acordo ao encontrado em outros genes de LTPs de plantas. Por último, a PnLTP madura foi expressa em sistema bacteriano. Experimentos adicionais serão realizados com o objetivo de avaliar a habilidade da PnLTP recombinante em inibir o crescimento do F. solani f. sp. piperis.

Muitos laboratórios de eletrofisiologia visual não possuem seus próprios valores de normalidade para o eletrorretinograma de campo total. Isto prejudica a confiabilidade dos diagnósticos de diversas patologias que afetam as vias visuais. Desta forma, o objetivo deste trabalho foi estabelecer os valores normativos para o teste Eletrorretinograma de Campo Total para o Laboratório de Neurologia Tropical (LNT) da Universidade Federal do Pará (UFPA). Realizaram o eletrorretinograma 68 indivíduos saudáveis e sem queixas visuais divididos em três grupos de acordo com a faixa etária: 36 indivíduos pertenceram ao grupo 1 (entre 17 e 30 anos), 21 indivíduos ao grupo 2 (entre 31 e 45 anos) e 11 indivíduos ao grupo 3 (entre 46 e 60 anos). O protocolo de realização do teste seguiu as recomendações da ISCEV, com a utilização de seis tipos de estimulação. Quatro após adaptação escotópica e estimulação com intensidades de: 0,01 cd.s/m

A ansiedade é uma desordem complexa e com grande relevância clínica, cujo estudo com modelos animais é importante para pesquisar sobre seus mecanismos e drogas para o seu tratamento.O

zebrafish figura como um potencial modelo animal para pesquisas farmacológicas da ansiedade. Um modelo de ansiedade é a preferência claro-escuro, que já foi validado comportamentalmente em zebrafish, contudo necessita de uma validação farmacológica. Objetiva-se descrever a sensibilidade da preferência claro-escuro em zebrafish adultos para as drogas mais utilizadas na clínica da ansiedade, foram administradas pela imersão do animal na solução: Benzodiazepínicos (Clonazepam); Agonistas parciais 5-HT1A (Buspirona); Antidepressivo tricíclico (Imipramina); Antidepressivo ISRS (Fluoxetina e Paroxetina); Antipsicóticos (Haloperidol e Risperidona); Psicostimulante (Dietilpropiona); Beta bloqueadores (Propranolol) e Depressores do SNC (Etanol). Os parâmetros analisados foram o tempo despendido pelo animal no ambiente escuro, o tempo da primeira latência e número de alternâncias. O clonazepam administrado por 300s aumentou o tempo no escuro na menor concentração e reduziu a atividade locomotora, a administração durante 600s da concentração intermediária diminuiu o tempo no escuro e da primeira latência, assim como aumentou a atividade locomotora, indicando efeito ansiolítico. A buspirona aumentou o tempo de permanência no escuro provavelmente devido a redução da atividade motora. A imipramina e a fluoxetina aumentaram o tempo no escuro e da primeira latência e diminuíram o número de alternâncias, indicando ação ansiogênica. A paroxetina não alterou o tempo no escuro, entretanto aumentou o tempo da primeira latência e diminuiu a atividade locomotora. O haloperidol diminuiu a ansiedade na menor concentração, curiosamente aumentou a atividade motora na maior concentração, ao contrário da risperidona que diminuiu a atividade na maior concentração. A dietilpropriona não modificou o tempo no escuro, mas aumentou o tempo da primeira latência e diminuiu a atividade motora apenas na menor concentração. O propranolol reduziu somente o tempo no escuro. O etanol foi efetivo na redução da ansiedade com a concentração intermediária e diminuiu a atividade locomotora em uma concentração menor Os dados corroboram com relatos da literatura em Danio rerio tanto neste modelo em administração intraperitoneal como em outros modelos por administração hídrica e em roedores, quando foi possível a comparação.

Os gliomas são a forma mais agressiva de câncer cerebral sendo resistentes a várias terapias incluindo neurocirurgia, radioterapia ou quimioterapia. Entretanto, muitos esforços têm sido feitos para identificação de componentes bioativos com atividades biológicas que poderão ajudar na descoberta e desenvolvimento de novas drogas contra o glioma maligno. Alguns destes componentes são os derivados sintéticos das isoxazolonas. Assim, investigamos os efeitos dos derivados isoxazólicos em células de glioma de rato da linhagem C6. A viabilidade celular foi avaliada pelo ensaio do MTT. Seis componentes (Isox 2, 3, 4, 7, 8 e 10) foram testados mas somente quatro deles (Isox2, 3, 4 and 10) produziram uma redução dose dependente na viabilidade destas células. A análise da morfologia nuclear utilizou o ensaio Hoechst 33342, como marcador fluorescente de ADN. Após o tratamento com quatro derivados isoxazólicos, na concentração de 100μM, por 24 horas a 37ºC, a linhagem gliomal testada apresentou condensação da cromatina. Pela análise ultraestrutural, a microscopia eletrônica evidenciou alterações morfológicas significativas na linhagem celular tratada, quando comparada com o controle. As células expostas ao tratamento apresentaram morfologia de padrão ovóide, com núcleo apresentando condensação e fragmentação da cromatina, contudo mantendo suas membranas nuclear e plasmática intactas. A mitocôndria demonstrou ingurgitamento e desorganização de suas cristas e membrana interna respectivamente. Os resultados indicam que os derivados isoxazólicos apresentaram citotoxidade nas células C6, induzindo a morte celular por apoptose ao mesmo tempo em que não tiveram nenhum efeito citotóxico em células de retina de galinha, usadas como controle sob as mesmas condições.

As neoplasias astrocitárias correspondem a cerca de (60%) dos tumores do

sistema nervoso central, sendo que atingem principalmente adultos numa fase

altamente produtiva da vida e com evoluções pouco satisfatórias apesar dos

tratamentos disponíveis. Um melhor entendimento de sua biologia molecular se

faz necessário na tentativa de compreender sua evolução e melhor planejar e

tratamento, assim como na busca de novas terapias. Este trabalho teve como

objetivo analisar modificações no gene

e polimorfismos nos éxons de 4 a 11, considerados

Um total de 14 amostras de diferentes graus de malignidade foram analisadas

por experimentos de FISH interfásico com sondas loco-específicas do gene

A exposição a compostos mercuriais resulta em danos oxidativos, afetando gravemente o sistema nervoso central, como observado em humanos e em modelos experimentais. Este trabalho utilizou ratos Wistar em diferentes períodos do neuro-desenvolvimento a fim de investigar possíveis efeitos protetores do selênio (selenito de sódio) em um modelo

in vivo de exposição ao metilmercúrio (MeHg). Os sujeitos (grupos de idades P1 e P21) receberam por amamentação ou via oral: veículo, Selênio (5ppm), MeHg (10ppm) ou Selênio (5ppm) mais MeHg (10ppm) durante 20 e 10 dias respectivamente (n = 8 por grupo). Após o tratamento, os ratos foram submetidos aos testes de campo aberto e labirinto aquático a fim de analisar déficits motores e de memória/aprendizagem, respectivamente. Para fins de análise histológica, foi realizada perfusão e imunohistoquimica para Neu-N. Com o objetivo de aferir possíveis efeitos deletérios sobre populações neuronais, foi feita contagem estereológica dos neurônios do hipocampo (camada polimórfica do giro denteado). Como resultado, foi observada redução significativa na atividade locomotora de neonatos (P1) mediante exposição ao MeHg. Além disso, nos grupos expostos ao MeHg (isoladamente ou associado ao selênio) verificou-se déficits de aprendizagem e memória. Já os animais P21 expostos ao MeHg apresentaram aumento na atividade locomotora, efeito abolido pela administração concomitante de selênio. Quando submetidos ao labirinto aquático, observou-se redução do tempo de latência apenas no grupo controle e naqueles animais expostos ao selênio. Como resultado das contagens estereológicas, observou-se diminuição do número de neurônios no hipocampo somente nos animais P21 expostos ao mercúrio. Os resultados obtidos sob estas condições experimentais mostraram que a exposição ao MeHg resultou em efeitos comportamentais diversos dependentes da idade dos sujeitos. A administração de selênio só foi capaz de interferir positivamente nos déficits locomotores observados em animais mais velhos. Além disso, foi observado que a administração de selênio não interferiu nos distúrbios comportamentais de memória/aprendizagem, tampouco na morte neuronal induzida por MeHg. Possíveis mecanismos associados a este padrão de proteção parcial por selênio, especialmente em estágios mais avançados de desenvolvimento neural ainda necessitam ser elucidados.

Foi estabelecido um modelo de imunossupressão em roedores por inoculação do agente alquilante Ciclofosfamida (CY). A administração de 50 mg/kg de CY em ratos Wistar provocou uma significante diminuição dos parâmetros de celularidade e peso relativo dos órgãos linfóides. Pela análise da titulação de anticorpos, do ensaio sobre as células formadoras de placa e do teste de hemólise foi comprovada que a imunidade humoral dos roedores sofreu supressão. Foram realizadas quatro inoculações desse imunossupressor e a periodicidade entre as inoculações foi determinada pela recuperação dos níveis de normalidade dos parâmetros supracitados. A alteração na contagem diferencial de células sanguíneas brancas representou o maior efeito adverso da CY, observado nos parâmetros de laboratório analisados nos Cebus apella. Nas duas vezes que foi administrada a droga houve redução no número de linfócitos e posteriormente diminuição de neutrófilos, porém somente na segunda foi observada a imunossupressão. Visto a proximidade filogenética dos primatas não humanos, este desenho experimental será de suma importância para o estudo de tumores em diversas fases do desenvolvimento e principalmente para testes de novos fármacos e esquemas terapêuticos. Com relação às análises de genotoxicidade da CY podemos concluir que em ratos Wistar, as administrações de CY aumentaram significativamente a freqüência de micronúcleos em eritrócitos policromáticos (MN PCEs) e provocaram efeito citotóxico (P<0.05). Em C. apella, os linfócitos do sangue periférico, após o tratamento com CY apresentaram um aumento significativo da media de MN/1000 células em relação aos linfócitos controle (P<0.05). A concentração de CY de 50mg/kg, em C. apella, corresponde à concentração DL50 da droga, visto que 50% desses animais morreram durante o experimento de imunossupressão. Até o desenvolvimento deste trabalho, não se conhecia a concentração correspondente ao DL50 nessa espécie. Ao comparamos as duas espécies de animais utilizadas neste trabalho, os primatas não humanos têm uma recuperação imune mais rápida em relação aos ratos Wistar. Provavelmente a capacidade de metabolização da droga seja mais eficaz em C. apella. Nossos resultados apóiam, portanto, que os primatas não humanos constituem os melhores modelos experimentais devido a sua grande proximidade evolutiva e filogenética com o ser humano.

Devido sua composição rica em sais minerais, proteínas, carboidratos, vitaminas e indutores da divisão celular (fitohormônios) (NUNES & COMBARNOUS, 1995; SANTOSO et al., 1996; SILVA et al. 2009) a água de coco, há alguns anos, vem sendo empregada com sucesso dentro das biotecnologias reprodutivas, principalmente, como diluente de sêmen de várias espécies como suínos (TONIOLLI & MESQUITA, 1990; BARROS, 2010), caprinos e ovinos (ARAÚJO & NUNES, 1990; NUNES, 1997; NUNES & SALGUEIRO, 1999), bubalinos (VALE et al., 1999), peixes (FARIAS et al., 1999), cães (UCHOA et al., 2002, 2003; CARDOSO et al., 2003, 2005, 2006), felinos (SILVA et al. 2007), primatas (ARAÚJO et al., 2009) e até mesmo humanos (NUNES, 1998).

O grande sucesso da água de coco em promover maior viabilidade aos espermatozóides incentivou sua utilização na preservação de outros tipos celulares como folículos ovarianos pré-antrais

Quando os meios de cultivo empregados na ativação e crescimento de folículos ovarianos primordiais foram suplementados com água de coco

A leishmaniose é considerada um problema de saúde pública, principalmente devido à presença de diferentes espécies enzoóticas de Leishmania, envolvendo muitos hospedeiros e diferentes insetos vetores. Os antimoniais pentavalentes permanecem como as drogas de primeira escolha para o tratamento das leishmanioses há mais de 50 anos, no entanto, sua utilização vem sendo comprometida devido, principalmente, a resistência desenvolvida pelo parasita ao medicamento. Assim, a escolha de drogas derivadas de plantas baseada no estudo e utilização de práticas da medicina tradicional devem aparecer como nova estratégia para o controle da leishmaniose. No entanto, é importante verificar que algumas destas drogas podem ser tóxicas ao organismo, podendo inclusive apresentar propriedades genotóxicas, causando alterações no DNA com conseqüente aumento no risco de carcinogênese. A Julocrotina (2-[N-(2-methylbutanolyl)]- N-phenylethylglutarimide) é um alcalóide glutarimida isolado da espécie Croton pullei var. glabrior Lanj. (Euphorbiaceae), encontrada amplamente na Floresta Amazônica e conhecido por possuir potente efeito leishmanicida. Desta forma, no presente estudo avaliamos o efeito citotóxico e genotóxico da Julocrotinaa partir do Ensaio do MTT e Ensaio do Cometa (versão alcalina) em cultura de linfócitos humanos. Como resultado, o alcalóide não demonstrou citotoxicidade em linfócitos humanos nas concentrações testadas. No entanto, a julocrotina mostrou-se genotóxica para linfócitos humanos tratados com a maior concentração (632μM) da substância. Apesar dos resultados de citotoxicidade parecem promissores no que diz respeito aouso da julocrotina no tratamento da leishmaniose, o efeito genotóxico observado reforça anecessidade de se obter as devidas precauções quanto ao seu uso como fitoterápico leishmanicida.