RESUMEN
Soy phytoestrogens have been proposed as an alternative to estrogen replacement therapy and have demonstrated potential neuroprotective effects in the brain. We have shown that a high soy diet significantly reduces infarct size following permanent middle cerebral artery occlusion (MCAO). Here, we tested the hypothesis that a high soy diet would attenuate programmed cell death after stroke. Adult female Sprague-Dawley rats were ovariectomized and fed either an isoflavone-reduced diet (IFP) or a high soy diet (SP) for 2 weeks before undergoing 90 min of transient middle cerebral artery occlusion (tMCAO) followed by 22.5 h reperfusion. Infarct size, as assessed by triphenyltetrazolium chloride staining, was significantly reduced by a high soy diet (P<0.05). Apoptosis in the ischemic cortex, measured by TUNEL staining, was significantly reduced by the high soy diet. The number of active caspase-3 positive cells and caspase-mediated alpha-spectrin cleavage were also significantly decreased in the ischemic cortex of SP rats. Furthermore, nuclear translocation of apoptosis-inducing factor (AIF) was significantly reduced in the ischemic cortex of SP rats. Soy significantly increased bcl-x(L) mRNA and protein expression in the ischemic cortex compared with IFP rats. Immunohistochemistry revealed increased neuronal expression of bcl-2 and bcl-x(L) in the ischemic cortex of both IFP and SP rats following tMCAO. These results suggest that a high soy diet decreases both caspase-dependent and caspase-independent programmed cell death following tMCAO. Further, a high soy diet enhances expression of the cell survival factor bcl-x(L) following tMCAO, contributing to the neuroprotective effects of soy in the ischemic cortex.
Asunto(s)
Apoptosis/efectos de los fármacos , Degeneración Nerviosa/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Fitoestrógenos/farmacología , Accidente Cerebrovascular/tratamiento farmacológico , Proteína bcl-X/efectos de los fármacos , Transporte Activo de Núcleo Celular/efectos de los fármacos , Transporte Activo de Núcleo Celular/genética , Animales , Apoptosis/genética , Factor Inductor de la Apoptosis/efectos de los fármacos , Factor Inductor de la Apoptosis/genética , Factor Inductor de la Apoptosis/metabolismo , Proteínas Reguladoras de la Apoptosis/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/fisiopatología , Caspasas/efectos de los fármacos , Caspasas/genética , Caspasas/metabolismo , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Modelos Animales de Enfermedad , Estrógenos/metabolismo , Femenino , Alimentos Formulados , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/genética , Infarto de la Arteria Cerebral Media/metabolismo , Degeneración Nerviosa/genética , Degeneración Nerviosa/metabolismo , Fármacos Neuroprotectores/metabolismo , Fármacos Neuroprotectores/uso terapéutico , Fitoestrógenos/metabolismo , Fitoestrógenos/uso terapéutico , Proteínas Proto-Oncogénicas c-bcl-2/efectos de los fármacos , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , ARN Mensajero/efectos de los fármacos , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Alimentos de Soja , Accidente Cerebrovascular/genética , Accidente Cerebrovascular/metabolismo , Proteína bcl-X/genética , Proteína bcl-X/metabolismoRESUMEN
This report describes a case in which the diagnosis of sickle cell disease (SCD) was established after death. The diagnosis of sickle cell syndrome was made in a 68 year old black patient who was found to have sickled red blood cells in many organs at necropsy although the disease had not been diagnosed during her lifetime. DNA was isolated from a peripheral blood smear obtained on the day of the patient's death. The beta globin gene was polymerase chain reaction amplified and sequenced, revealing that the patient had S-beta(+) thalassaemia. This study shows that blood smears are a suitable source for retrospective DNA analysis studies. This case illustrates that relatively "mild" forms of SCD can be overlooked, despite symptomatology suggestive of a sickle syndrome, and demonstrates the feasibility of the postmortem molecular diagnosis of haemoglobinopathies in such cases.