RESUMEN
The present study aimed to investigate the behavioral and anticonvulsant effects of lamotrigine (LTG) on the genetic audiogenic seizure hamster (GASH:Sal), an animal model of audiogenic seizure that is in the validation process. To evaluate the efficiency of acute and chronic treatments with LTG, GASH:Sals were treated with LTG either acutely via intraperitoneal injection (5-20mg/kg) or chronically via oral administration (20-25mg/kg/day). Their behavior was assessed via neuroethological analysis, and the anticonvulsant effect of LTG was evaluated based on the appearance and the severity of seizures. The results showed that acute administration of LTG exerts an anticonvulsant effect at the lowest dose tested (5mg/kg) and that chronic oral LTG treatment exerts an anticonvulsant effect at a dose of 20-25mg/kg/day. Furthermore, LTG treatment induced a low rate of secondary adverse effects. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic".
Asunto(s)
Anticonvulsivantes/uso terapéutico , Modelos Animales de Enfermedad , Epilepsia Refleja/tratamiento farmacológico , Convulsiones/tratamiento farmacológico , Triazinas/uso terapéutico , Animales , Anticonvulsivantes/farmacología , Cricetinae , Relación Dosis-Respuesta a Droga , Epilepsia Refleja/genética , Epilepsia Refleja/fisiopatología , Etología/métodos , Lamotrigina , Masculino , Mesocricetus , Convulsiones/genética , Convulsiones/fisiopatología , Resultado del Tratamiento , Triazinas/farmacologíaRESUMEN
Epilepsy modeling is essential for understanding the basic mechanisms of the epileptic process. The Genetic Audiogenic Seizure Hamster (GASH:Sal) exhibits generalized tonic-clonic seizures of genetic origin in response to sound stimulation and is currently being validated as a reliable model of epilepsy. Here, we performed a pharmacological and neuroethological study using well-known and widely used antiepileptic drugs (AEDs), including phenobarbital (PB), valproic acid (VPA), and levetiracetam (LEV). The intraperitoneal administration of PB (5-20mg/kg) and VPA (100-300mg/kg) produced a dose-dependent decrease in GASH:Sal audiogenic seizure severity scores. The administration of LEV (30-100mg/kg) did not produce a clear effect. Phenobarbital showed a short plasmatic life and had a high antiepileptic effect starting at 10mg/kg that was accompanied by ataxia. Valproic acid acted only at high concentrations and was the AED with the most ataxic effects. Levetiracetam at all doses also produced sedation and ataxia side effects. We conclude that the GASH:Sal is a reliable genetic model of epilepsy suitable to evaluate AEDs.
Asunto(s)
Anticonvulsivantes/uso terapéutico , Conducta Animal/efectos de los fármacos , Epilepsia Refleja/complicaciones , Epilepsia Refleja/tratamiento farmacológico , Estimulación Acústica/efectos adversos , Animales , Anticonvulsivantes/sangre , Anticonvulsivantes/farmacología , Cromatografía Líquida de Alta Presión , Cricetinae , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Epilepsia Refleja/genética , Proteínas de Homeodominio/genética , Levetiracetam , Locomoción/efectos de los fármacos , Masculino , Espectrometría de Masas , Fenobarbital/sangre , Fenobarbital/farmacología , Fenobarbital/uso terapéutico , Piracetam/análogos & derivados , Piracetam/sangre , Piracetam/farmacología , Piracetam/uso terapéutico , Factores de Tiempo , Factores de Transcripción/genética , Ácido Valproico/sangre , Ácido Valproico/farmacología , Ácido Valproico/uso terapéuticoRESUMEN
The objective of the study was to assess the clinical, histopathological and immunochemical changes induced by dialyzable leukocyte extract (DLE) treatment in patients with chronic cervicitis associated to HPV infection. Fifty-four female Mexican patients diagnosed with chronic cervicitis, cervical intra-epithelial neoplasia grade 1 (CIN 1) and HPV infection were divided into two groups: patients treated with placebo and patients treated with DLE. Clinical and colposcopy evaluations were performed before and after treatments. Cervix biopsies were obtained to analyze histopathological features and to determine the local immunological changes by immunohistochemistry analyses. Placebo-treated patients showed no significant changes in the evaluated parameters. Interestingly, in DLE-treated patients, clinical manifestations of cervicitis diminished and 89% of them remitted the colposcopic lesions. Histological analyses of biopsies from DLE-treated patients showed a decreasing leukocyte infiltrate. Immunochemical analyses showed an increased expression of TGF-ß, while expression of IFN-γ, PCNA, and IL-32 decreased. Our results suggest that DLE can stimulate innate immunity of cervical mucosae, diminishing chronic cervicitis in HPV-infected patients. TRIAL REGISTRATION: Register ISRCTN16429164 Abbreviations: HPV = Human Papilloma Virus; DLE = Dialyzable leukocyte extract.
Asunto(s)
Infecciones por Papillomavirus/complicaciones , Factor de Transferencia/uso terapéutico , Cervicitis Uterina/complicaciones , Cervicitis Uterina/tratamiento farmacológico , Adulto , Anciano , Biopsia , Cuello del Útero/diagnóstico por imagen , Cuello del Útero/patología , Enfermedad Crónica , Colposcopía , Femenino , Humanos , Inmunohistoquímica , Interferón gamma/metabolismo , Interleucinas/metabolismo , Persona de Mediana Edad , Infecciones por Papillomavirus/virología , Antígeno Nuclear de Célula en Proliferación/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Cervicitis Uterina/diagnóstico por imagen , Cervicitis Uterina/patología , Adulto JovenRESUMEN
The purpose of this study was to determine the photoprotective properties of the methanolic extract of Buddleja scordioides, as well as verbascoside and linarin which were isolated from this extract, and linarin acetate prepared in the laboratory. The photoprotective effect of substances against UV-B induced cellular death was evaluated by challenge experiments using Escherichia coli. Verbascoside and linarin acetate showed the highest protection. The sun protection factor (SPF) of the methanolic extract, linarin, linarin acetate, and verbascoside was evaluated by guinea pig bioassays. Verbascoside showed the largest SPF measurement.