RESUMEN
Stroke is a heterogeneous syndrome caused by multiple disease mechanisms, resulting in a disruption of cerebral blood flow with subsequent tissue damage. It is well known that erythrocytes have a large amount of sialic acid and could represent a model to investigate changes occurring in a pathology like stroke. The aim of this study was to investigate a possible relationship among erythrocyte membrane, plasma and sialic acid content. The possible impact of the sialic acid content and the activity of sialidase on stroke severity was also evaluated. The study population consisted of 54 patients with a first stroke and of 53 age-and sex matched healthy volunteers. The total bound sialic acid was substantially decreased in patients. There was a significant correlation between the sialidase activity values and the severity of the neurological deficit defined by the National Institute of Health Stroke Scale. This study shows that low sialic acid erythrocyte concentrations with contemporary high sialic acid plasma levels and elevated sialidase activity can be considered as markers of ischemic stroke. Further investigations are needed to clarify the possible role of these biochemical changes in producing and sustaining cerebral ischemic damage.
Asunto(s)
Ácido N-Acetilneuramínico/sangre , Neuraminidasa/sangre , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/enzimología , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Membrana Eritrocítica/enzimología , Membrana Eritrocítica/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Plasma/enzimología , Plasma/metabolismoRESUMEN
Production of reactive oxygen species after cerebral blood flow disruption may enhance tissue damage through multiple molecular pathways. Changes in nitric oxide (NO) metabolism and oxidative stress status were investigated in 47 patients with ischemic stroke by measuring plasma nitric oxide (NO) and peroxynitrite (ONOO(-)) levels.A correlation was sought between these two parameters and i) baseline stroke severity based on the National Institute of Health stroke scale (NIHSS) and ii) neurological outcome in terms of NIHSS changes from entry (T(0)) to 30 days after symptom onset (T(1)). The control group consisted of 30 age- and sex-matched healthy subjects. Mean plasma levels of ONOO(-) (arbitrary fluorescence number +/- SD) were significantly higher in patients (7.70 +/- 1.71 vs 5.35 +/- 0.69, p < 0.001), whereas mean NO levels (nmol/mg protein) were significantly higher in controls (115.40 +/- 12.40 vs. 51.10 +/- 12.50, p < 0.001). Plasma ONOO(-) was significantly higher among patients with non-lacunar stroke (8.48 +/- 1.50 vs. 6.95 +/- 1.58 in those with lacunar stroke; p = 0.001), whereas NO levels were significantly higher among lacunar stroke patients (60.00 +/- 7.86, vs. 41.77 +/- 9.29 in patients with nonlacunar stroke; p < 0.001). Nitric oxide plasma levels were also associated with an unfavorable evolution in non-lacunar stroke, since a 10 unit increase in NO predicted a 1 point reduction in the NIHSS score at T1. Findings show that changes in NO metabolism may be considered as markers of brain injury in patients with ischemic stroke. Further work is needed to establish whether the amount of biochemical changes related to oxidative stress may influence outcome in these patients.
Asunto(s)
Encéfalo/metabolismo , Encéfalo/fisiopatología , Óxido Nítrico/sangre , Estrés Oxidativo/fisiología , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/fisiopatología , Edad de Inicio , Anciano , Anciano de 80 o más Años , Biomarcadores/análisis , Biomarcadores/sangre , Infarto Encefálico/sangre , Infarto Encefálico/fisiopatología , Isquemia Encefálica/sangre , Isquemia Encefálica/fisiopatología , Progresión de la Enfermedad , Femenino , Radicales Libres/sangre , Humanos , Masculino , Persona de Mediana Edad , Ácido Peroxinitroso/sangre , Índice de Severidad de la Enfermedad , Regulación hacia Arriba/fisiologíaRESUMEN
Previous investigations have suggested that changes in platelet activity may play a key role in the pathophysiology of migraine via mechanisms involving the nitric oxide (NO) pathway. Changes in platelet response and nitrite levels have recently been demonstrated during migraine attacks, while there is considerable uncertainty about NO activity in headache-free periods. A reactive oxidant produced from NO and superoxide anion at the site of inflammation, peroxynitrite (ONOO-) has effects including changes in membrane activity and fluidity. The aim of the present study was to determine ONOO- levels in the platelets of patients suffering from migraine during the headache-free period. Nitric oxide synthase (eNOS and iNOS) expression in platelets and the effects of ONOO- on membrane Na+/K+-ATPase activity and membrane fluidity were also evaluated. Subjects were 57 patients suffering from migraine without aura and 35 controls. Blood samples were collected in the headache-free period. Platelet ONOO- levels were determined using dichlorofluorescein acetate with steady-state fluorescence. Platelets were then probed for induction of eNOS and iNOS expression by western immunoblotting. Membrane Na+/K+-ATPase activity and fluidity were determined with the fluorescent probes TMA-DPH and DPH. In the presence of extracellular l-arginine(100 micromol/l), ONOO- production was significantly greater in patients' platelets than in those of controls (P < 0.001). Western immunoblotting of platelet proteins evidenced higher iNOS expression in patients than in controls. In addition, platelet membrane Na+/K+-ATPase activity and membrane fluidity evaluated by TMA-DPH were significantly lower in patients (P < 0.001). In conclusion, migraine patients show intercritic changes in platelet membrane fluidity and activity that may be related to the oxidative stress caused by increased ONOO- levels.
Asunto(s)
Plaquetas/metabolismo , Fluidez de la Membrana/fisiología , Trastornos Migrañosos/sangre , Ácido Peroxinitroso/biosíntesis , Adulto , Femenino , Humanos , MasculinoRESUMEN
The purpose of this study was to evaluate the efficacy of topiramate in the treatment of chronic migraine. This was a double-blind, randomized, placebo controlled, parallel-group study. Patients suffering from chronic migraine with analgesic overuse were randomly assigned in a 1 : 1 ratio to receive topiramate or placebo. Following a baseline phase of eight weeks, the study drug was titrated in 25-mg increments over one week to 50 mg daily. Titration phase was followed by a 8-week maintenance phase. Number of days with headache during a 28-day period was the efficacy variable. At baseline, there was no difference in the number of days with headache between patients treated with topiramate and those treated with placebo (mean +/- SD: 20.9 +/- 3.2 and 20.8 +/- 3.2, respectively). During the last 4 week-maintenance phase, topiramate-treated patients experienced a significantly lower 28-day headache frequency in comparison to those treated with placebo (mean number of days with headache +/- SD: 8.1 +/- 8.1 vs. 20.6 +/- 3.4, P < 0.0007). Topiramate at low doses proved to be an effective therapeutic approach to reduce headache frequency in patients with chronic migraine and analgesic overuse.