RESUMEN
OBJECTIVE: To determine whether there are any associations between the -258T/G polymorphism of the promoter and the IVS3 -20T/C polymorphism in parkin gene and Parkinson's disease (PD) from a Han population in Sichuan province. METHODS: Polymerase chain reaction (PCR), restriction fragment length polymorphism, denaturing high performance liquid chromatography(dHPLC) and sequence analysis were used to determine the genotype of each subject. The -258T/G polymorphism and IVS3 -20T/C polymorphism were analysed in 198 patients with sporadic PD and 187 healthy controls, matched for age and gender. RESULTS: There were significant differences in allele frequency of the -258T/G polymorphism between PD patients and controls, with the G allele more common in cases than controls (52.5% vs 43.3%; chi square is 6.17, P< 0.025, OR is 1.45, 95% CI 1.04-1.86). There were also significant differences in G allele frequency between PD patients with onset age over 50 years old and controls(chi square is 9.048, P< 0.01, OR is 1.57, 95% CI:1.08-2.06). The frequency of TG+GG genotype was significantly higher in PD patients than in controls (78.79% vs 69.51%; chi square is 3.854, P< 0.05, OR is 1.63, 95% CI:0.88-2.38). In addition, there were significant differences in age of onset between PD patients with different genotypes (P< 0.05). The average age of onset in group of GG genotype was later about 5 years compared with the group of TT or TG genotype. The frequency of CC genotype in IVS3 -20T/C polymorphism was much higher than that of TC genotype. No TT genotype was found. CONCLUSION: This study suggests that the parkin promoter -258T/G polymorphism might be a risk factor for late onset PD in Sichuan. CC genotype for IVS3 -20T/C polymorphism is common in Sichuan Han population. No TT genotype for IVS3 -20T/C polymorphism is found in Sichuan Han population.
Asunto(s)
Enfermedad de Parkinson/genética , Ubiquitina-Proteína Ligasas/genética , Adulto , Anciano , Anciano de 80 o más Años , Pueblo Asiatico/genética , China , Cromatografía Líquida de Alta Presión , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/etnología , Reacción en Cadena de la Polimerasa , Polimorfismo Genético , Polimorfismo de Longitud del Fragmento de Restricción , Regiones Promotoras Genéticas/genéticaRESUMEN
OBJECTIVE: To investigate the effect of batroxobin on K+ channel activated by Ca2+ in primary cultured cortex neurons of fetal SD rat. METHODS: The patch clamp technique of single channel recordings including cell-attach and inside-out mode was used. RESULTS: Extracellular batroxobin activated the Kca. In Ca2+ bath solution of cell-attach mode, Vp +30 mV, when the concentrations of batroxobin were 0.15, 0.25, 0.50, 0.75 and 1.0 mmol/L, the open probabilities of the channel were 0.013 +/- 0.002, 0.082 +/- 0.011, 0.131+/- 0.012, 0.211+/- 0.010 and 0.062 +/- 0.009 (P < 0.01), respectively. It appeared concentration-dependent within 0.75 mmol/ L. batroxobin. In Ca2+ free-bath solution of cell-attach mode, Vp+50 mV, when the concentrations of batroxobin were 0.15, 0.40, 0.60 and 1.0 mmol/L, the open probabilities of the channel were 0.013 +/- 0.001, 0.112 +/- 0.007, 0.193 +/- 0.010 and 0.301 +/- 0.009 (P < 0.05), respectively. In the 6 cases of inside-out mode patch clamp, Vp +40 mV, when the concentrations of batroxobin were 0, 0.25 and 0.50 mmol/L, the open probabilities of the channel were 0. 012 +/- 0.007, 0.011 +/- 0.009 and 0.013 +/- 0.008 (P > 0.05), respectively. There was no significant difference in open probabilities, average open/close times and amplitudes at different intracellular batroxobin concentrations. CONCLUSION: Batroxobin can affect the activation of the Kca channel through regulating the concentration of cytoplasmic free Ca2+. It may have a protective effect on neurons.
Asunto(s)
Batroxobina/farmacología , Corteza Cerebral/metabolismo , Neuronas/metabolismo , Canales de Potasio Calcio-Activados/efectos de los fármacos , Animales , Animales Recién Nacidos , Células Cultivadas , Corteza Cerebral/citología , Relación Dosis-Respuesta a Droga , Femenino , Masculino , Neuronas/citología , Técnicas de Placa-Clamp , Ratas , Ratas Sprague-DawleyRESUMEN
AIM: To observe the effects of Ca2+ -activated K+ channel of primary cultured fetal SD rat cortex neurons in the veratridine triggered neuronal damage. METHODS: The patch clamp technique of cell-attach and inside-out mode for these two kinds of single channel recordings were used. RESULTS: Extracellular veratridine activated the Kca. In Ca2+ bath solution of cell-attach mode, Vp + 30 mV, when the concentration (micromol/L) of veratridine were 15,25,50 and 75, the open probabilities of the channel were 0.014 +/- 0.003, 0.085 +/- 0.010, 0.132 +/- 0.016 and 0.059 +/- 0.006 (P < 0.01) respectively. It appeared concentration-dependent within 50 micromol/L veratridine. In Ca2+ free bath solution of cell-attach mode, Vp = +50 mV, when the concentration (micromol/L) of veratridine were 15, 40,60 and 100, the open probabilities of the channel were 0.014 +/- 0.010, 0.113 +/- 0.006, 0.141 +/- 0.004 and 0.295 +/- 0.009 (P < 0.05) respectively. In the 6 cases of inside-out mode patch clamp, Vp = +40 mV, when the concentration of veratridine were 0, 25 micromol/L and 50 micromol/L, the open probabilities of the channel were 0.011 +/- 0.008, 0.010 +/- 0.010 and 0.012 +/- 0.007 (P > 0.05) respectively. There were no significant difference on open probabilities, average open/close times and amplitudes at different intracellular veratridine concentration. CONCLUSION: Veratridine can affect the activation of the Kca channel through regulating the concentration of cytoplasmic free Ca2+. The opening of Kca activated by increase of intracellular Ca2+ during the early stage of anoxia may be a protection reaction of ischemic neurons.
Asunto(s)
Neuronas/efectos de los fármacos , Neuronas/fisiología , Canales de Potasio Calcio-Activados/metabolismo , Veratridina/farmacología , Animales , Animales Recién Nacidos , Calcio/metabolismo , Células Cultivadas , Neuronas/citología , Técnicas de Placa-Clamp , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND AND PURPOSE: The goal of this article is to clarify the proportion of stroke subtypes in China, where stoke is the most common cause of death. METHODS: A total of 16,031 first-ever strokes in subjects >or=25 years of age were identified in 1991 to 2000 from 17 Chinese populations through a community-based cardiovascular disease surveillance program in the China Multicenter Collaborative Study of Cardiovascular Epidemiology. World Health Organization diagnosis criteria were used for classification of stroke subtypes. RESULTS: CT scan rate of stroke cases reached a satisfactorily high level only after 1996 in the study populations. In 8268 first-ever stroke events from 10 populations with CT scan rate >75% in 1996 to 2000, 1.8% were subarachnoid hemorrhage, 27.5% were intracerebral hemorrhage, 62.4% were cerebral infarction, and 8.3% were undetermined stroke. The proportion of intracerebral hemorrhage varied from 17.1% to 39.4% and that for cerebral infarction varied from 45.5% to 75.9% from population to population. The ratio of ischemic to hemorrhagic stroke ranged from 1.1 to 3.9 and averaged 2.0). The 28-day fatality rate was 33.3% for subarachnoid hemorrhage, 49.4% for intracerebral hemorrhage, 16.9% for cerebral infarction, and 64.6% for undetermined stroke. CONCLUSIONS: In our study, ischemic stroke was more frequent and its proportion was higher than hemorrhagic stroke in Chinese populations. Although hemorrhagic stroke was more frequent in Chinese than in Western populations, the variation in the proportion of stroke subtypes among Chinese populations could be as large as or larger than that between Chinese and Western populations.
Asunto(s)
Accidente Cerebrovascular/clasificación , Accidente Cerebrovascular/epidemiología , Adulto , Distribución por Edad , Edad de Inicio , Anciano , Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/epidemiología , Infarto Cerebral/diagnóstico , Infarto Cerebral/epidemiología , China/epidemiología , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Mortalidad , Vigilancia de la Población , Población Rural/estadística & datos numéricos , Distribución por Sexo , Accidente Cerebrovascular/diagnóstico , Hemorragia Subaracnoidea/diagnóstico , Hemorragia Subaracnoidea/epidemiología , Tomografía Computarizada por Rayos X/estadística & datos numéricos , Población Urbana/estadística & datos numéricosRESUMEN
OBJECTIVE: To study the ratio of ischemic to hemorrhagic stroke incidence in Chinese populations. METHODS: Fifteen populations in China, each including about 100,000 residents, were monitored from 1991 to 2000 for the occurrence of stroke. Stroke was classified as hemorrhagic, ischemic and unclassified based on the clinical data and CT scan results respectively. RESULTS: The average CT scan rate in stroke patients from 1996 to 2000 varied from 14.8% to 97.5% among the 15 population and the average ratio of ischemic to hemorrhagic stroke ranged from 0.23:1 to 4.38:1; the correlation coefficient between the ratio and CT scan rate is 0.7 (P = 0.003). In all the populations with CT scan rate greater than 80%, the ischemic to haemorrhagic ratios were all greater than 1.0. From 1991 to 2000 in 12 populations with complete data, the CT scan rate in stroke patients rose from 41.1% to 88.3% and the ischemic to hemorrhagic ratio rose from 1.25:1 to 1.85:1. The correlation coefficient between the ratio and the CT scan rate was 0.9 (P < 0.001). In patients having CT scan, the ischemic to hemorrhagic ratio was greater than 1.0 in all the years. CONCLUSION: The predominant type of stroke in Chinese population is ischemic. The low CT scan rate in some populations is the main reason for the false impression predominantly hemorrhagic stroke.