Plos One
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Hypoxia-inducible factor 1 (HIF-1) is a master regulator of cellular adaptation to hypoxia and has been suggested as a potent therapeutic target in cerebral ischemia. Here we show in an ischemic stroke model of rats that inhibiting HIF-1 and its downstream genes by 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) significantly increases mortality and enlarges infarct volume evaluated by MRI and histological staining. Interestingly, the HIF-1 inhibition remarkably ameliorates ischemia-induced blood-brain barrier (BBB) disruption determined by Evans blue leakage although it does not affect brain edema. ⋯ Further analyses show that ischemia upregulates HIF-1 and its downstream genes erythropoietin (EPO), vascular endothelial growth factor (VEGF), and glucose transporter (Glut) in neurons and brain endothelial cells and that YC-1 inhibits their expression. We postulate that HIF-1-induced VEGF increases BBB permeability while certain other proteins coded by HIF-1's downstream genes such as epo and glut provide neuroprotection in an ischemic brain. The results indicate that YC-1 lacks the potential as a cerebral ischemic treatment although it confers certain protection to the cerebral vascular system.
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The prevalence of IgE mediated food allergies has increased over the last two decades. Food allergy has been reported to be fatal in highly sensitive individuals. Legumes are important food allergens but their prevalence may vary among different populations. The present study identifies sensitization to common legumes among Indian population, characterizes allergens of kidney bean and establishes its cross reactivity with other legumes. ⋯ Among legumes, kidney bean followed by chick pea and peanut are the major allergic triggers in asthma and rhinitis patients in India. Kidney bean showed eight major allergens and cross reacted with other legumes. A combination of SPT, sIgE and histamine release assay is helpful in allergy diagnosis.
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Traumatic brain injury (TBI) remains a leading cause of death and disability. The National Institute for Health and Clinical Excellence (NICE) guidelines recommend transfer of severe TBI cases to neurosurgical centres, irrespective of the need for neurosurgery. This observational study investigated the risk-adjusted mortality of isolated TBI admissions in England/Wales, and Victoria, Australia, and the impact of neurosurgical centre management on outcomes. ⋯ The risk-adjusted odds of mortality for all isolated TBI admissions, and severe TBI cases, were higher in England/Wales when compared to Victoria. The lower percentage of cases managed at neurosurgical centres in England and Wales was an explanatory factor, supporting the changes made to the NICE guidelines.
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Recent studies have reported that patients with end-stage heart disease can have cognitive deficits ranging from mild to severe. Little is known, however, about the relationship between cognitive performance, neurophysiological characteristics and relevant clinical and instrumental indexes for an extensive evaluation of patients with heart failure, such as: left ventricular ejection fraction (LVEF) and other haemodynamic measures, maximum oxygen uptake during cardiopulmonary exercise testing, comorbidities, major cardiovascular risk factors and disease duration. Our purpose was to outline the cognitive profiles of end-stage heart disease patients in order to identify the cognitive deficits that could compromise the quality of life and the therapeutic adherence in end-stage heart disease patients, and to identify the variables associated with an increased risk of cognitive deficits in these patients. ⋯ Severe heart failure induces significant neurophysiological and neuropsychological alterations, which may produce an impairment of cognitive functioning and possibly compromise the quality of life of patients and the therapeutic adherence.
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Secundum-type atrial septal defects (ASDII) account for approximately 10% of all congenital heart defects (CHD) and are associated with a familial risk. Mutations in transcription factors represent a genetic source for ASDII. Yet, little is known about the role of mutations in sarcomeric genes in ASDII etiology. ⋯ No mutations were found in the 11 other sarcomeric genes analyzed. The study indicates that sarcomeric gene mutations may represent a so far underestimated genetic source for familial recurrence of ASDII. In particular, perturbations in the MYH6 head domain seem to play a major role in the genetic origin of familial ASDII.