Abstract Background The fact that inflammation triggers epileptic seizures brings to mind the antiepileptic properties of anti-inflammatory drugs. Objective To investigate the electrophysiological and anti-inflammatory effects of fingolimod on an experimental penicillin-induced acute epileptic seizure model in rats. Methods Thirty-two male Wistar rats were divided into four groups: control (penicillin), positive control (penicillin + diazepam [5 mg/kg]), drug (penicillin + fingolimod [0.3 mg/kg]) and synergy group (penicillin + diazepam + fingolimod). The animals were anesthetized with urethane, and epileptiform activity was induced by intracortical injection of penicillin (500,000 IU). After electrophysiological recording for 125 minutes, IL-1β, TNF-α, and IL-6 were evaluated by ELISA in the serum of sacrificed animals. Results During the experiment, animal deaths occurred in the synergy group due to the synergistic negative chronotropic effect of diazepam and fingolimod. Although not statistically significant, fingolimod caused a slight decrease in spike-wave activity and spike amplitudes in the acute seizure model induced by penicillin (p > 0.05). Fingolimod decreased serum IL-1β (p < 0.05); fingolimod and diazepam together reduced IL-6 (p < 0.05), but no change was observed in serum TNF-α values. Conclusion Even in acute use, the spike-wave and amplitude values of fingolimod decrease with diazepam, anticonvulsant and anti-inflammatory effects of fingolimod will be more prominent in chronic applications and central tissue evaluations. In addition, concomitant use of fingolimod and diazepam is considered to be contraindicated due to the synergistic negative inotropic effect.

Resumo Antecedentes O fato de a inflamação desencadear crises epilépticas traz à mente as propriedades antiepilépticas dos anti-inflamatórios. Objetivo Investigar os efeitos eletrofisiológicos e anti-inflamatórios do fingolimode em um modelo experimental de crise epiléptica aguda induzida por penicilina em ratos. Métodos Trinta e dois ratos Wistar machos foram divididos em quatro grupos: controle (penicilina), controle positivo (penicilina + diazepam [5 mg/kg]), droga (penicilina + fingolimode [0,3 mg/kg]) e grupo sinergia (penicilina + diazepam + fingolimode). Os animais foram anestesiados com uretano, e a atividade epileptiforme foi induzida por injeção intracortical de penicilina (500.000 UI). Após registro eletrofisiológico por 125 minutos, IL-1β, TNF-α e IL-6 foram avaliados por ELISA no soro dos animais sacrificados. Resultados Durante o experimento, ocorreram mortes de animais no grupo sinérgico devido ao efeito cronotrópico negativo sinérgico do diazepam e do fingolimode. Embora não seja estatisticamente significativo, o fingolimode causou uma ligeira diminuição na atividade pico-onda e nas amplitudes pico no modelo de convulsão aguda induzida pela penicilina (p > 0,05). O fingolimode diminuiu a IL-1β sérica (p < 0,05); fingolimode e diazepam juntos reduziram a IL-6 (p < 0,05), mas não foi observada alteração nos valores séricos de TNF-α. Conclusão Pensa-se que o efeito anticonvulsivante leve de uma dose única de fingolimode será mais proeminente em aplicações crônicas e em avaliações de tecidos centrais. Além disso, o uso concomitante de fingolimode e diazepam é considerado contraindicado devido ao efeito inotrópico negativo sinérgico.

RESUMO A vortioxetina é um agente antidepressivo multimodal que modula os receptores 5HT e inibe o transportador de serotonina. Está indicada, principalmente nos casos de transtorno depressivo maior (TDM), relacionado à disfunção cognitiva. Existem muitos estudos que investigam os efeitos dos antidepressivos no limiar convulsivo e na atividade epiléptica de curto prazo. No entanto, o efeito da vortioxetina nas crises epilépticas não é exatamente conhecido. Nosso objetivo é investigar os efeitos da vortioxetina sobre a atividade epileptiforme induzida pela penicilina. Vinte e sete ratos Wistar foram divididos em três grupos, grupo controle-sham, grupo controle positivo (Diazepam) e grupo vortioxetina. Depois, 0,1 mg (10 mg / kg) de vortioxetina foi administrado no grupo vortioxetina, e 0,1 ml (5 mg / kg) / kg) de diazepam foi administrado no grupo de controle positivo intraperitonealmente. Os registros de atividade epiléptica foram obtidos durante 120 minutos após o início da convulsão. Não houve diferença significativa na atividade de pico entre o grupo de voritoxetina e diazepam, embora tenha sido significativamente reduzida no grupo de vortioxetina em comparação com os controles. A administração de vortioxetina na dose de 10 mg / kg imediatamente após a indução das convulsões diminuiu significativamente as frequências de espícula da atividade epileptiforme em comparação com o grupo controle. Nenhuma diferença significativa foi encontrada entre a vortioxetina e controles positivos. Este estudo mostrou que a vortioxetina reduz o número de descargas epilépticas agudamente induzidas. A vortioxetina pode ser uma alternativa importante para pacientes epilépticos com disfunção cognitiva relacionada à TDM.

ABSTRACT Vortioxetine is a multimodal antidepressant agent that modulates 5-HT receptors and inhibits the serotonin transporter. It is indicated especially in cases of major depressive disorder related to cognitive dysfunction. There are many studies investigating the effects of antidepressants on the seizure threshold and short-term epileptic activity. However, the effect of vortioxetine on epileptic seizures is not exactly known. Our aim was to investigate the effects of vortioxetine on penicillin-induced epileptiform activity. Twenty-seven Wistar rats were divided into three groups: sham-control group, positive control group (diazepam), and vortioxetine group. After a penicillin-induced epilepsy model was formed in each of the three groups of animals, 0.1 ml of saline was administered to the control group, 0.1 ml (10 mg/kg) vortioxetine was administered in the vortioxetine group, and 0.1 mL (5 mg/kg) of diazepam was administered in the positive control group, intraperitoneally. The epileptic activity records were obtained for 120 minutes after the onset of seizure. There was no significant difference in spike wave activity between the vortioxetine and diazepam groups, whereas this was significantly reduced in the vortioxetine group compared with the controls. The administration of vortioxetine at a dose of 10 mg/kg immediately after the seizure induction significantly decreased the spike frequencies of epileptiform activity compared with the control group. No significant difference was found between the vortioxetine and positive controls. This study showed that vortioxetine reduces the number of acutely-induced epileptic discharges. Vortioxetine may be an important alternative for epileptic patients with major depressive disorder-related cognitive dysfunction.

Abstract Purpose: To evaluate the clinical stenosis or precursor histological changes that ureteral access sheaths commonly used in ureteroscopic surgeries may cause in the long term in ureter. Methods: In this study, the animals were divided into 9 groups and according to their groups, ureters of the rabbits were endoscopically fitted with 2F and 3F ureter catheters. The catheters were left in place and withdrawn after a specified period of time. All the ureters were excised and evaluated macroscopically, microscopically and histologically. Ureter diameters were measured and FGF-2 (+) labeled fibroblasts were counted in connective tissue as stenosis precursors. Results: Macroscopically or microscopically, no stenosis was found in any group. The ureter diameter of the group that were catheterized for the longest time with the catheter that had the widest diameter was significantly lower than the group with the shorter duration and the catheter with the narrower diameter and the control group. When the groups were compared in terms of their FGF values, there was a significant difference in FGF-2 counts at all three ureter levels (p <0.05). Conclusion: The use of ureteral access sheath may lead to histological changes, as its diameter and duration increase.