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1.
J Alzheimers Dis ; 71(3): 1063-1069, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31476161

RESUMEN

Oxidative stress is part of the entire pathological process that underlies the development of Alzheimer's disease (AD), including the mild cognitive impairment (MCI) stage. Twendee X (TwX) is a supplement containing a strong antioxidative mix of eight antioxidants, which has been shown to have a clinical and therapeutic benefit in AD model mice. Here, we conducted a multicenter, randomized, double-blind, and placebo-controlled prospective interventional study to evaluate the efficacy of TwX in mitigating MCI. The primary outcomes were differences in Mini-Mental State Examination (MMSE) and Hasegawa Dementia Scale-revised (HDS-R) scores between baseline and six months for placebo and TwX groups. Seventy-eight subjects with MCI were randomized into placebo (n = 37) and TwX (n = 41) groups. MMSE scores at six months differed significantly between the TwX and placebo groups (p = 0.018), and HDS-R scores for the TwX group exhibited a significant improvement at six months relative to baseline (p = 0.025). The TwX group did not show any change in affective or activities of daily living scores at six months. The present study indicates that strong antioxidative supplement TwX is clinical beneficial for cognitive function in subjects with MCI.


Asunto(s)
Antioxidantes/uso terapéutico , Ácido Ascórbico/uso terapéutico , Disfunción Cognitiva/tratamiento farmacológico , Cistina/uso terapéutico , Suplementos Dietéticos , Glutamina/uso terapéutico , Actividades Cotidianas , Anciano , Anciano de 80 o más Años , Cognición , Disfunción Cognitiva/psicología , Método Doble Ciego , Femenino , Humanos , Masculino , Pruebas de Estado Mental y Demencia , Estudios Prospectivos , Resultado del Tratamiento
2.
J Stroke Cerebrovasc Dis ; 27(8): 2096-2105, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29793801

RESUMEN

BACKGROUND: Dietary supplement is an attempt to reduce the risk of ischemic stroke in high-risk population. A new mixed vitamin E-Tocovid that mainly contains tocotrienols other than tocopherol, attenuated the progression of white matter lesions by oral in humans. However, the effect of Tocovid on ischemic stroke has not been examined. In the present study, we assessed the therapeutic effects of Tocovid pretreatment on transient middle cerebral artery occlusion (tMCAO) in mice. MATERIALS AND METHODS: After pretreatment with Tocovid (200 mg/kg/d) or vehicle for 1 month, 60-minute tMCAO was performed, and these mice were examined at 1 day, 3 days, and 7 days after reperfusion. We histologically assessed the effects of Tocovid pretreatment on the expressive changes of oxidative stress markers, cleaved caspase-3, and LC3-II after tMCAO in mice. RESULTS: We observed that Tocovid pretreatment significantly improved the rotarod time, reduced infarct volume, decreased the number of 4-HNE, nitrotyrosine, and 8-OhdG positive cells, inhibited advanced glycation end products biomarkers RAGE, CMA, and CML expressions, and increased Nrf2 and MRP1 levels with GSSG/GSH ratio decrease. Furthermore, Tocovid pretreatment greatly decreased cleaved caspase-3 and LC3-II expressions after tMCAO. CONCLUSIONS: The present study obviously demonstrated that Tocovid pretreatment showed neuroprotective effects against oxidative stress and at least in part by antiapoptotic/autophagic cell death in ischemic mice brain.


Asunto(s)
Antioxidantes/farmacología , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Tocotrienoles/farmacología , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Caspasa 3/metabolismo , Modelos Animales de Enfermedad , Glutatión/metabolismo , Productos Finales de Glicación Avanzada/metabolismo , Infarto de la Arteria Cerebral Media/metabolismo , Infarto de la Arteria Cerebral Media/patología , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Masculino , Ratones Endogámicos ICR , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo/fisiología , Distribución Aleatoria , Prueba de Desempeño de Rotación con Aceleración Constante , Factores de Tiempo
3.
Intern Med ; 57(10): 1455-1458, 2018 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-29321424

RESUMEN

A 37-year-old man with anti-muscle-specific tyrosine kinase (MuSK) antibody-positive myasthenia gravis (MG) presented with subacute progressive dysphagia and muscle weakness of the neck and bilateral upper extremities. Conventional immune-suppressive treatments and high-dose intravenous immunoglobulin were ineffective. He then displayed repeated exacerbations and remissions over the course of two years, despite two to four sessions of plasma exchange (PE) every two months. The patient was successfully treated with outpatient periodic weekly blood purification therapy with alternative PE and double-filtration plasmapheresis using an internal shunt. This case report suggests the benefits of blood purification therapy with an internal shunt against anti-MuSK antibody-positive MG.


Asunto(s)
Atención Ambulatoria , Autoanticuerpos/sangre , Miastenia Gravis/inmunología , Miastenia Gravis/terapia , Intercambio Plasmático , Plasmaféresis , Proteínas Tirosina Quinasas Receptoras/inmunología , Receptores Colinérgicos/inmunología , Adulto , Trastornos de Deglución/etiología , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Masculino , Debilidad Muscular/etiología , Miastenia Gravis/diagnóstico , Tirosina/uso terapéutico
4.
J Neurosci Res ; 95(9): 1818-1828, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28035779

RESUMEN

This study aimed to assess the risk of intracerebral hemorrhage (ICH) after tissue-type plasminogen activator (tPA) treatment in rivaroxaban compared with warfarin-pretreated male Wistar rat brain after ischemia in relation to activation profiles of protease-activated receptor-1, -2, -3, and -4 (PAR-1, -2, -3, and -4). After pretreatment with warfarin (0.2 mg/kg/day), low-dose rivaroxaban (60 mg/kg/day), high-dose rivaroxaban (120 mg/kg/day), or vehicle for 14 days, transient middle cerebral artery occlusion was induced for 90 min, followed by reperfusion with tPA (10 mg/kg/10 ml). Infarct volume, hemorrhagic volume, immunoglobulin G leakage, and blood parameters were examined. Twenty-four hours after reperfusion, immunohistochemistry for PARs was performed in brain sections. ICH volume was increased in the warfarin-pretreated group compared with the rivaroxaban-treated group. PAR-1, -2, -3, and -4 were widely expressed in the normal brain, and their levels were increased in the ischemic brain, especially in the peri-ischemic lesion. Warfarin pretreatment enhanced the expression of PAR-1 and PAR-2 in the peri-ischemic lesion, whereas rivaroxaban pretreatment did not. The present study shows a lower risk of brain hemorrhage in rivaroxaban-pretreated compared with warfarin-pretreated rats following tPA administration to the ischemic brain. It is suggested that the relative downregulation of PAR-1 and PAR-2 by rivaroxaban compared with warfarin pretreatment might be partly involved in the mechanism of reduced hemorrhagic complications in patients receiving rivaroxaban in clinical trials. © 2016 Wiley Periodicals, Inc.


Asunto(s)
Hemorragia Cerebral , Inhibidores del Factor Xa/farmacología , Rivaroxabán/farmacología , Animales , Anticoagulantes/farmacología , Hemorragia Cerebral/metabolismo , Regulación hacia Abajo , Fibrinolíticos/farmacología , Masculino , Ratas , Ratas Wistar , Receptor PAR-1/biosíntesis , Receptor PAR-2/biosíntesis , Accidente Cerebrovascular/complicaciones , Terapia Trombolítica/efectos adversos , Terapia Trombolítica/métodos , Activador de Tejido Plasminógeno/farmacología , Warfarina/farmacología
5.
J Stroke Cerebrovasc Dis ; 25(8): 1997-2003, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27230587

RESUMEN

BACKGROUND: Warfarin and rivaroxaban are highly effective in reducing stroke risk in patients with atrial fibrillation (AF). However, their effects on anticoagulation and neurovascular unit (NVU) change remain elusive. In this study, we assessed the risks and benefits of pre-treatment with warfarin or rivaroxaban after tissue-type plasminogen activator (tPA) thrombolysis in ischemic rat brain. METHODS: Pre-treatment with warfarin (.2 mg/kg/day), low dose rivaroxaban (60 mg/kg/day), high dose rivaroxaban (120 mg/kg/day) or vehicle was performed for 2 weeks, transient middle cerebral artery occlusion (tMCAO) was induced for 90 min, then followed by reperfusion with tPA. At 24 hours (h) after reperfusion, we observed the changes of matrix metalloproteinase-9 (MMP-9), tissue factor, caspase 3 and NVU dissociation. RESULTS: Prothrombin time (PT) was significantly prolonged in the warfarin and rivaroxaban pretreated groups. MMP-9 expression greatly increased in the warfarin group, and this was reduced in the rivaroxaban groups compared with the vehicle group. Tissue factor expression remarkably decreased in the warfarin and rivaroxaban groups. The number of caspase 3-positive cells had no difference among all the groups. Marked dissociations between astrocyte foot processes and the basal lamina or pericytes were observed in the warfarin pretreated group, but such dissociations were improved in the rivaroxaban groups. CONCLUSIONS: Our present study shows that pre-treatment with rivaroxaban was noninferior to warfarin in the anticoagulation, but a lower risk of NVU dysfunction and dissociation after tPA treatment in rivaroxaban. This finding could partly explain the mechanism of reducing hemorrhagic complications by rivaroxaban in clinical studies.


Asunto(s)
Anticoagulantes/administración & dosificación , Encéfalo , Regulación de la Expresión Génica/efectos de los fármacos , Infarto de la Arteria Cerebral Media/prevención & control , Rivaroxabán/administración & dosificación , Warfarina/administración & dosificación , Animales , Peso Corporal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Caspasa 3/metabolismo , Colágeno/metabolismo , Modelos Animales de Enfermedad , Esquema de Medicación , Proteína Ácida Fibrilar de la Glía/metabolismo , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Lectinas de Plantas/metabolismo , Ratas , Ratas Wistar , Receptores del Factor de Crecimiento Derivado de Plaquetas/metabolismo
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