ABSTRACT
OBJECTIVE: Refractory status epilepticus is one of the most life-threatening neurological emergencies and is characterized by high morbidity and mortality. Additionally, the use of anti-inflammatory drugs during this period is very controversial. Thus, this study has been designed to analyze the effect of a low dose of indomethacin (a COX inhibitor) on the expression of inflammatory molecules. METHOD: The hippocampus of rats submitted to pilocarpine-induced long-lasting status epilepticus was analyzed to determine the expression of inflammatory molecules with RT-PCR and immunohistochemistry. RESULTS: Compared with controls, reduced levels of the kinin B2 receptors IL1β and TNFα were found in the hippocampus of rats submitted to long-lasting status epilepticus and treated with indomethacin. CONCLUSIONS: These data show that low doses of indomethacin could be employed to minimize inflammation during long-lasting status epilepticus. .
Subject(s)
Animals , Male , Cyclooxygenase Inhibitors/pharmacology , Hippocampus/drug effects , Indomethacin/pharmacology , Monokines/drug effects , Receptors, Bradykinin/drug effects , Status Epilepticus/drug therapy , Disease Models, Animal , Down-Regulation/drug effects , Interleukin-1beta/analysis , Interleukin-1beta/drug effects , Monokines/analysis , Pilocarpine , Rats, Wistar , Receptor, Bradykinin B1/analysis , Receptor, Bradykinin B1/drug effects , /analysis , /drug effects , Receptors, Bradykinin/analysis , Status Epilepticus/chemically induced , Tumor Necrosis Factor-alpha/analysis , Tumor Necrosis Factor-alpha/drug effectsABSTRACT
Background: Gender can influence post-infarction cardiac remodeling. Objective: To evaluate whether gender influences left ventricular (LV) remodeling and integrin-linked kinase (ILK) after myocardial infarction (MI). Methods: Female and male Wistar rats were assigned to one of three groups: sham, moderate MI (size: 20-39% of LV area), and large MI (size: ≥40% of LV area). MI was induced by coronary occlusion, and echocardiographic analysis was performed after six weeks to evaluate MI size as well as LV morphology and function. Real-time RT-PCR and Western blot were used to quantify ILK in the myocardium. Results: MI size was similar between genders. MI resulted in systolic dysfunction and enlargement of end-diastolic as well as end-systolic dimension of LV as a function of necrotic area size in both genders. Female rats with large MI showed a lower diastolic and systolic dilatation than the respective male rats; however, LV dysfunction was similar between genders. Gene and protein levels of ILK were increased in female rats with moderate and large infarctions, but only male rats with large infarctions showed an altered ILK mRNA level. A negative linear correlation was evident between LV dimensions and ILK expression in female rats with large MI. Conclusions: Post-MI ILK expression is altered in a gender-specific manner, and higher ILK levels found in females may be sufficient to improve LV geometry but not LV function. .
Fundamento: O gênero pode ser decisivo no remodelamento cardíaco após infarto do miocárdio. Objetivo: Avaliar diferenças de gênero associadas ao remodelamento do ventrículo esquerdo (VE) após infarto do miocárdio (IM) e associadas à modulação de quinases acopladas à integrina (integrin-linked kinases-ILK). Métodos: Ratos Wistar machos e fêmeas foram divididos em 3 grupos: grupo sham, grupo com IM de extensão moderada (tamanho: 20-39% da área do VE); grupo com IM de grande extensão (tamanho: ≥ 40% da área do VE). O IM foi produzido por oclusão coronária e as análises ecocardiográficas foram obtidas após 6 semanas para avaliar a extensão do IM, bem como a morfologia e função do VE. RT-PCR em tempo real e Western blott foram realizados para quantificar a ILK no miocárdio. Resultados: A extensão do IM foi semelhante entre os gêneros. O IM resultou em disfunção sistólica e aumento do tamanho do VE no final da diástole e da sístole em função do tamanho da área necrótica para ambos os sexos. Ratos fêmeas com IM de grande extensão apresentaram dilatação diastólica e sistólica inferior a de ratos machos, mas a disfunção do VE foi semelhante em ambos os sexos. Os níveis gênicos e proteicos de ILK aumentaram em ratos fêmeas com infartos de extensão moderada e grande, mas apenas ratos machos com infartos de grande extensão apresentaram níveis alterados de mRNA do ILK. Uma correlação linear negativa foi observada entre as dimensões do VE e a expressão de ILK em ratos fêmeas com IM de grande extensão. Conclusões: A expressão de ILK pós-IM variou de maneira gênero-especifica, e os níveis mais elevados de ILK observados em ...