RESUMO
Abstract Due to the fact that different isoforms of carbonic anhydrase play distinct physiological roles, their diseases/disorders involvement are different as well. Involvement in major disorders such as glaucoma, epilepsy, Alzheimer's disease, obesity and cancers, have turned carbonic anhydrase into a popular case study in the field of rational drug design. Since carbonic anhydrases are highly similar with regard to their structures, selective inhibition of different isoforms has been a significant challenge. By applying a proteochemometrics approach, herein the chemical interaction space governed by acyl selenoureido benzensulfonamides and human carbonic anhydrases is explored. To assess the validity, robustness and predictivity power of the proteochemometrics model, a diverse set of validation methods was used. The final model is shown to provide valuable structural information that can be considered for new selective inhibitors design. Using the supplied information and to show the applicability of the constructed model, new compounds were designed. Monitoring of selectivity ratios of new designs shows very promising results with regard to their selectivity for a specific isoform of carbonic anhydrase.
Assuntos
Selênio/agonistas , Desenho de Fármacos , Anidrases Carbônicas/análise , Anidrases Carbônicas/efeitos adversos , Isoformas de Proteínas , Epilepsia/patologia , Doença de Alzheimer/patologia , Neoplasias/patologiaRESUMO
Introduction. Eighty-five percent of all epileptics live in tropical regions. Prenatal risk factors, traumatic braininjuries and different parasitic infestations of the central nervous system (CNS) are the reasons behind the high prevalence ofepilepsy. This work reviews the main parasitic infestations causing epilepsy in the tropics. Development. Neurocysticercosis isthe main cause of focal epilepsy in early adulthood in endemic areas (30-50%). All the phases of cysticerci (viable, transitionaland calcified) are associated with epileptic seizures. Anti-cysticercus treatment helps get rid of cysticerci faster and reducesthe risk of recurrence of seizures in patients with viable cysts. Symptomatic epilepsy can be the first manifestation of neuroschistosomiasisin patients without any systemic symptoms. The pseudotumoral form can trigger seizures secondary to thepresence of granulomas and oedemas in the cerebral cortex. The eggs of Schistosoma japonicum are smaller, reach the CNSmore easily and trigger epileptic seizures more frequently. Toxocariasis and sparganosis are other parasitic infestations thatcan give rise to symptomatic seizures. The risk factors for suffering chronic epilepsy after cerebral malaria are a positivefamilial history of epilepsy and a history of episodes of fever and cerebral malaria that began with coma or which progressedwith multiple, prolonged epileptic seizures. About 20% of patients with cerebral infarction secondary to Chagas diseasepresent late vascular epilepsy as a complication. Conclusions. Very few studies have been conducted to examine the prognosis,risk of recurrence and modification of the natural course of seizures associated with tropical parasitic infestations, except forthe case of neurocysticercosis (AU)
Introducción. El 85% de las personas epilépticas vive en regiones tropicales. Factores de riesgo prenatales, traumatismoscraneoencefálicos y diversas parasitosis del sistema nervioso central (SNC) explican la elevada prevalencia de epilepsia.Se revisan las principales parasitosis tropicales causantes de epilepsia. Desarrollo. La neurocisticercosis es la principalcausa de epilepsia focal de inicio en la vida adulta en áreas endémicas (30-50%). Todas las fases de los cisticercos (viables,transicionales y calcificados) se asocian con crisis epilépticas. El tratamiento cisticida favorece la desaparición más rápidade los cisticercos y reduce el riesgo de recurrencia de crisis en pacientes con quistes viables. La epilepsia sintomáticapuede ser la primera manifestación de la neuroesquistosomiasis en pacientes sin síntomas sistémicos. La forma pseudotumoralpuede provocar crisis secundarias a la presencia de granulomas y edema en la corteza cerebral. Los huevos de Schistosomajaponicum son más pequeños, alcanzan más fácilmente el SNC y provocan crisis epilépticas más frecuentemente. Toxocariasisy esparganosis son otras helmintiasis que pueden provocar crisis sintomáticas. Los factores de riesgo de padecer epilepsiacrónica después de malaria cerebral son una historia familiar positiva para epilepsia, y antecedentes de crisis febrilesy de malaria cerebral que comenzó con coma o que cursó con crisis epilépticas múltiples y prolongadas. Alrededor del 20%de los pacientes con infarto cerebral secundario a enfermedad de Chagas presenta como complicación una epilepsia vasculartardía. Conclusiones. Los estudios sobre el pronóstico, riesgo de recurrencia y modificación del curso natural de las crisisasociadas a las parasitosis tropicales son escasos, a excepción de la neurocisticercosis (AU)
Assuntos
Humanos , Masculino , Feminino , Epilepsia/diagnóstico , Epilepsia/epidemiologia , Epilepsia/etiologia , Epilepsia/patologia , Epilepsia/parasitologia , Ecossistema Tropical/efeitos adversos , Ecossistema Tropical/análise , Medicina Tradicional/história , Parasitos/crescimento & desenvolvimento , Parasitos/patogenicidadeRESUMO
Objetivo. Analizar la utilidad de los registros por video-electroencefalograma (VEEG) en régimen ambulatorio realizados en un servicio de neurología general para la detección de un episodio crítico. Pacientes y métodos. Desde el 1 de junio de 1999 hasta el 1 de junio de 2003 realizamos 105 exploraciones por VEEG, de 30 minutos a 5 horas de duración, en pacientes con crisis de etiología no aclarada, ante la sospecha de pseudocrisis o en presencia de una epilepsia farmacorresistente y crisis muy frecuentes. No modificamos la medicación del paciente para realizar la exploración. Resultados. En 33 pacientes se registraron eventos clínicos patológicos; en 14 se trató de crisis epilépticas, en 12 de pseudos crisis, en 4 de síncopes y en 3 de movimientos anormales no epilépticos. La duración del registro fue de 30 minutos en 12, de entre 30 minutos y 2 horas en 12 y de más de 2 horas en 9 pacientes. En 18 pacientes el VEEG fue la exploración diagnóstica. En un caso cambió el diagnóstico del tipo de crisis epiléptica que sufría el paciente, y en 11 pacientes nos ayudó a caracterizar sus crisis epilépticas. Conclusión. Si bien el porcentaje de registro de eventos patológicos durante un estudio por VEEG ambulatorio de 30 minutos a 5 horas de duración es bajo, su repercusión clínica es muy alta y el coste añadido, escaso
Objective. To analyze the utility of outpatient videoelectroencephalogram (VEEG) in a general neurology department to detect an ictal event. Patients and methods. One hundred and five patients with ictal phenomenology of unknown etiology, suspicion of pseudoseizures, refractory epilepsy with very frequent seizures, underwent outpatient VEEG monitoring from 30 minutes to five hours of duration, between June 1, 1999 and June 30, 2003. Patient medication was not modified to perform the recording. Results. Among the 105 outpatient VEEG monitoring, 33 clinical pathologic events were identified; these comprised 14 epileptic seizures, 12 pseudoseizures, four syncopes, and three non epileptic abnormal movements. Outpatient VEEG monitoring duration was as follows: 30 minutes in 12 patients, between 30 minutes and two hours in another 12, and more than two hours in 9. In 19 patients, the VEEG recording allowed a definitive diagnosis; in one case, it changed the epileptic seizure type, and in 11 patients, it helped to better characterize the epileptic seizure type. Conclusion. Although the percentage of pathologic events during an outpatient VEEG monitoring of 30 minutes to five hours of duration is low, its clinical repercussion is very important and the added cost is low