The pilocarpine model in rodents reproduces the main features of mesial temporal lobe epilepsy related to hippocampus sclerosis (MTLE-HS) in humans. It has been demonstrated in this model that the phosphorylation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluR1 subunit is increased 1 h after pilocarpine treatment. Moreover, alterations in the levels of glutamate transporters have been associated with chronic epilepsy in humans. Despite these studies, the profile of these changes has not yet been addressed. We analyzed the protein content and phosphorylation profile of the AMPA receptor GluR1 subunit by western blotting. We also used quantitative real-time polymerase chain reaction to analyze the expression of glial glutamate transporters and the N-methyl-D-aspartate receptor NR1 subunit in the hippocampus (Hip) and cerebral cortex (Ctx) at different time points after pilocarpine-induced status epilepticus (Pilo-SE) in male adult Wistar rats. Biochemical analysis was performed in the Hip and Ctx at 1, 3, 12 h (acute period), 5 days (latent period), and 50 days (chronic period) after Pilo-SE. Key findings include an increase in the phosphorylation of GluR1-Ser(845) in the Ctx and GluR1-Ser(831) in the Hip at different times during the acute period, and a decrease in the total content of the GluR1 subunit in the Ctx in the latent period. There was a down-regulation of the mRNA expression and protein levels of EAAT1 and EAAT2, and a decrease of the NR1 mRNA expression, in the Ctx during the latent period. Notably, during the chronic period, the EAAT2 mRNA expression and protein levels decreased while the NR1 mRNA levels increased in the Hip. Taken together, our findings suggest a time- and structure-dependent imbalance of glutamatergic transmission in response to Pilo-SE, which might be associated with either epileptogenesis or the seizure threshold in MTLE-HS.

Background and purpose Severe diarrhoea, a common gastrointestinal manifestation of anticancer treatment with irinotecan, might involve single nucleotide polymorphisms (SNPs) of toll‐like receptors (TLRs), described as critical bacterial sensors in the gut. Here, colorectal cancer patients carrying missense TLR4 A896G (rs4986790) or C1,196T (rs4986791) SNPs and Tlr4 knockout (Tlr4−/−) mice were given irinotecan to investigate the severity of the induced diarrhoea. Experimental approach Forty‐six patients treated with irinotecan‐based regimens had diarrhoea severity analysed according to TLR4 genotypes. In the experimental setting, wild‐type (WT) or Tlr4−/− mice were given irinotecan (45 or 75 mg·kg−1, i.p.) or saline (3 ml·kg−1). Diarrhoea severity was evaluated by measuring intestinal injury and inflammatory markers expression after animals were killed. Key results All patients with TLR4 SNPs chemotherapy‐treated presented diarrhoea, whereas gastrointestinal toxicity was observed in 50% of the wild homozygous individuals. Mice injected with irinotecan presented systemic bacterial translocation and increased TLR4 immunostaining in the intestine. In line with the clinical findings, Tlr4 gene deficiency enhanced irinotecan‐related diarrhoea and TLR9 expression in mice. An increased myeloperoxidase activity and Il‐18 expression along with IL‐10 decreased production in Tlr4−/− mice also indicated an intensified intestinal damage and inflammatory response. Conclusion and implications TLR4 deficiency upregulates TLR9 expression and enhances intestinal damage and the severity of late‐onset diarrhoea during irinotecan‐based treatment. Identifying patients genetically predisposed to chemotherapy‐associated diarrhoea is a strategy toward precision medicine.

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As doenças causadas pelos micro-organismos são seriamente agravadas pela resistência generalizada ocasionada pelo uso indiscriminado dos antimicrobianos. A busca por novos agentes antimicrobianos tornou-se o principal objetivo de muitos grupos de pesquisa. Muitos deles focando seu trabalho no Reino Plantae. Em face da capacidade evolutiva dos micro-organismos e apesar dos antibióticos sintéticos serem uma opção viável, o estudo dos Metabólitos Secundários das Plantas continua sendo um excelente ponto de partida para a descoberta de moléculas de potencial antimicrobiano. Portanto, neste trabalho foi verificada o efeito antimicrobiano do extrato aquoso e hidroalcoólico de folhas de Anacardium occidentale e Mangifera indica frente a bactérias multirresistentes empregando a técnica de poços por difusão em Agar. O presente estudo demonstrou que o extrato hidroalcoólico apresentou melhor atividade antimicrobiana quando comparado ao extrato aquoso. Nos ensaios de antibiose foi verificada atividade antibacteriana para espécie de Staphylococcus aureus quando exposto ao extrato aquoso de Anacardium occidentale na concentração de 150 mg.mL-1. Nenhuma das espécies estudadas apresentou inibição do crescimento quando expostas ao extrato aquoso de Mangifera indica. Os maiores halos de inibição ocorreram com o extrato hidroalcoólico de Anacardium occidentale frente à espécie de Staphylococcus aureus com a formação de um halo de inibição de 10 mm. Alguns processos devem ser considerados dentre eles, o procedimento utilizado para o isolamento e purificação dos Metabólitos Secundários das Plantas, o tipo de amostra estudada e a concentração adotada nos ensaios. A diversidade da metodologia aplicada contribuirá para uma melhor compreensão dos potenciais presentes nas plantas.

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