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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our long-term objective is to identify genes whose expression results in hypertension and in phenotypic changes that may contribute to hypertension. The purpose of the present study was to describe evidence for the heritability of hypertension-related phenotypes in hypertensive, hyperlipidemic black sib pairs. Outpatient anthropomorphic measurements were obtained in >200 affected sib pairs. In addition, 68 of these sib pairs were studied under controlled, standardized conditions at an inpatient clinical research center while off both antihypertensive and lipid-lowering medications. Heritability was estimated on the basis of sib-sib correlations and with an association model. Higher heritability estimates for blood pressure were observed with multiple measurements averaged over 24 hours than with measurements at a single time point, and heritability estimates for nighttime blood pressures were higher than those for daytime blood pressures. Heritability estimates for several of the phenotypes were augmented by obtaining measurements in response to a standardized stimulus, including (1) blood pressure responses to the assumption of upright posture, standardized psychological stress, and norepinephrine infusion; (2) plasma renin, aldosterone, epinephrine, and cAMP and cGMP responses to the assumption of upright posture; (3) para-aminohippurate and inulin clearances in response to norepinephrine infusion; and (4) plasma arginine vasopressin in response to NaCl infusion. High heritability estimates were also observed for various measures of body size and body fat, left ventricular size, cardiac index, stroke volume, total peripheral resistance, and serum concentrations of LDL and HDL cholesterol and leptin. These heritability estimates identify the hypertension-related phenotypes that may facilitate the identification of specific genetic determinants of hypertension in blacks with hyperlipidemia.
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PMID:Genetic determinants of hypertension: identification of candidate phenotypes. 1090 5

In males, aging, health and disease are processes that occur over physiologic time and involve a cascade of hormonal, biochemical and physiological changes that accompany the down-regulation of the hypothalamic-anterior pituitary-testicular axis. As aging progresses there are relative increases of body fat and decreases in muscle mass. The increased adipose tissue mass is associated with the production of a number of newly generated factors. These include aromatase, leptin, PAI-1, insulin resistance, and the dyslipidemias, all of which can lead to tissue damage. Fatty tissue becomes the focal point for study as it represents the intersection between energy storage and mobilization. The increase in adipose tissue is associated with an increase in the enzyme aromatase that converts testosterone to estradiol and leads to diminished testosterone levels that favor the preferential deposition of visceral fat. As the total body fat mass increases, hormone resistance develops for leptin and insulin. Increasing leptin fails to prevent weight gain and the hypogonadal-obesity cycle ensues causing further visceral obesity and insulin resistance. The progressive insulin resistance leads to a high triglyceride-low HDL pattern of dyslipidemia and increased cardiovascular risk. All of these factors eventually contribute to the CHAOS Complex: coronary disease, hypertension, adult-onset diabetes mellitus, obesity and/or stroke as permanent changes unfold. Other consequences of the chronic hypogonadal state include osteopenia, extreme fatigue, depression, insomnia, loss of aggressiveness and erectile dysfunction all of which develop over variable periods of time.
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PMID:Aromatase, adiposity, aging and disease. The hypogonadal-metabolic-atherogenic-disease and aging connection. 1139 22

Multiple endocrine abnormalities have been reported in stroke patients. In the past few years, it has been claimed that some of these abnormalities may play a role in worsening the neurological deficit and the outcome of stroke. Several mechanisms have been hypothesised, including a direct effect on the development of neuronal cell death, vasospasm, and development of brain edema. In this brief review, we discuss the current knowledge concerning the role of endothelin-1, arginine vasopressin, and cortisol in the pathogenesis of stroke. Finally, we discuss the possibility that leptin, the OB gene product, may be the link of some of these endocrine abnormalities, and that its abnormal secretion during stroke may contribute to the eating disorders and poor nutritional status often seen in these patients.
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PMID:Endocrine abnormalities and outcome of ischaemic stroke. 1168 80

Recent studies indicate that stress induces increased food intake only when stress is followed by a neuroendocrine reaction with increased cortisol concentrations. The stress of modern society may contribute to the current epidemic of abdominal obesity, which is characterised by increases in cortisol and leptin concentrations. This is a condition which carries a great risk for cardiovascular disease, type 2 diabetes mellitus and stroke.
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PMID:["Consolatory eating" is not a myth. Stress-induced increased cortisol levels result in leptin-resistant obesity]. 1176 60

Abnormalities in physical properties of the cell membranes may underlie the defects that are strongly linked to hypertension, stroke, and other cardiovascular diseases. Recently, there has been an indication that leptin, the product of the human obesity gene, actively participates not only in the metabolic regulations but also in the control of cardiovascular functions. In the present study, to assess the role of leptin in the regulation of membrane properties, the effects of leptin on membrane fluidity of erythrocytes in humans are examined. The membrane fluidity of erythrocytes in healthy volunteers by means of an electron paramagnetic resonance (EPR) and spin-labeling method is determined. In an in vitro study, leptin decreased the order parameter (S) for 5-nitroxide stearate (5-NS) and the peak height ratio (ho/h-1) for 16-NS obtained from EPR spectra of erythrocyte membranes in a dose-dependent manner in healthy volunteers. The finding indicated that leptin increased the membrane fluidity and improved the microviscosity of erythrocytes. The effect of leptin on the membrane fluidity was significantly potentiated by the nitric oxide (NO) donors, L-arginine and S-nitroso-N-acetylpenicillamine (SNAP), and a cyclic guanosine monophosphate (cGMP) analog, 8-bromo-cGMP. In contrast, the change evoked by leptin was significantly attenuated in the presence of the NO synthase inhibitors, N(G)-nitro-L-arginine-methyl-ester (L-NAME) and asymmetric dimethyl-L-arginine (ADMA). The results of the present study showed that leptin increased the membrane fluidity and improved the rigidity of cell membranes to some extent via an NO- and cGMP-dependent mechanism. Furthermore, the data also suggest that leptin might have a crucial role in the regulation of rheological behavior of erythrocytes and microcirculation in humans.
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PMID:Leptin improves membrane fluidity of erythrocytes in humans via a nitric oxide-dependent mechanism--an electron paramagnetic resonance investigation. 1227 Jan 47

Patients with sleep disordered breathing (SDB) are at increased risk for cardiovascular disease including hypertension, angina, myocardial infarction, and stroke. Neurohumoral and hemodynamic responses to untreated sleep apnea are likely mechanisms that produce functional and structural changes within the cardiovascular system. Obesity, higher blood pressure, and advancing age, which are common characteristics of patients with SDB, contribute to the overall risk for cardiovascular disease. Recent studies indicate that OSA is associated with or aggravates other risk markers for cardiovascular disease. These factors include leptin, C-reactive protein, homocysteine, and insulin resistance syndrome. Elevations in C-reactive protein and glucose intolerance may be correlated with the severity of SDB. The impact of alleviating SDB on these cardiovascular risk factors has not been fully elucidated. Regardless, assessment of overall cardiovascular risk in patients with sleep apnea is warranted to identify those individuals that are high-risk who require immediate attention and intervention or in those that should be treated more aggressively.
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PMID:Sleep disordered breathing and risk factors for cardiovascular disease. 1239 60

Although all cells in the body require energy to survive and function properly, excessive calorie intake over long time periods can compromise cell function and promote disorders such as cardiovascular disease, type-2 diabetes and cancers. Accordingly, dietary restriction (DR; either caloric restriction or intermittent fasting, with maintained vitamin and mineral intake) can extend lifespan and can increase disease resistance. Recent studies have shown that DR can have profound effects on brain function and vulnerability to injury and disease. DR can protect neurons against degeneration in animal models of Alzheimer's, Parkinson's and Huntington's diseases and stroke. Moreover, DR can stimulate the production of new neurons from stem cells (neurogenesis) and can enhance synaptic plasticity, which may increase the ability of the brain to resist aging and restore function following injury. Interestingly, increasing the time interval between meals can have beneficial effects on the brain and overall health of mice that are independent of cumulative calorie intake. The beneficial effects of DR, particularly those of intermittent fasting, appear to be the result of a cellular stress response that stimulates the production of proteins that enhance neuronal plasticity and resistance to oxidative and metabolic insults; they include neurotrophic factors such as brain-derived neurotrophic factor (BDNF), protein chaperones such as heat-shock proteins, and mitochondrial uncoupling proteins. Some beneficial effects of DR can be achieved by administering hormones that suppress appetite (leptin and ciliary neurotrophic factor) or by supplementing the diet with 2-deoxy-d-glucose, which may act as a calorie restriction mimetic. The profound influences of the quantity and timing of food intake on neuronal function and vulnerability to disease have revealed novel molecular and cellular mechanisms whereby diet affects the nervous system, and are leading to novel preventative and therapeutic approaches for neurodegenerative disorders.
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PMID:Meal size and frequency affect neuronal plasticity and vulnerability to disease: cellular and molecular mechanisms. 1255 61

Obstructive sleep apnoea (OSA) is a common disorder associated with an increased risk of cardiovascular disease and stroke. As it is strongly associated with known cardiovascular risk factors, including obesity, insulin resistance, and dyslipidemia, OSA is an independent risk factor for hypertension. Although the association between OSA and the metabolic syndrome tends to confound studies of the independent effects of OSA on vascular disease, recent evidences from basic science to epidemiological and clinical studies suggest that OSA may add worsening pathophysiological conditions to obesity. OSA contributes to the imbalance between vasodilators and vasoconstrictors, in particular through oxidative stress-dependent catabolism of nitric oxide, increased sympathetic nerve activity, enhanced renin-angiotensin system activity and endothelin synthesis. Additionally, several recent studies suggest that OSA may be a circumstance favouring central and vascular resistance to leptin. The beneficial effects of this hormone in normal subjects, are lost during endothelial dysfunction and OSA. Moreover, high leptin concentrations, within a range observed during OSA, display adverse effects on endothelial function and vascular physiology. Through of a yet unknown mechanism, OSA per se accounts for part of the elevated serum leptin concentration reported in patients. The current standard treatment for OSA-nasal continuous positive airway pressure (CPAP)-eliminates apnoea and the ensuing acute hemodynamic changes during sleep. Accordingly, vasopressor mediators and leptin concentration are shifted toward normal values by CPAP. Thus, in addition to this effective therapy, evaluation of specific strategies targeting leptin sensitivity and vasopressor mediators may open novel perspectives for treatment of OSA and its associated end-organ damages.
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PMID:[Effect of sleep apnea syndrome on the vascular endothelium]. 1464 10

1. We established a new animal model of metabolic syndrome, SHRSP fatty (fa/fa) rats, by crossing stroke-prone spontaneously hypertensive rats of the Izumo strain (SHRSP/Izm) to Zucker fatty (ZF) (fa/fa) rats. 2. The SHRSP fatty (fa/fa) rats have a missense mutation of the leptin receptor gene and plasma leptin concentrations are augmented. The SHRSP fatty (fa/fa) rats develop obesity and hypertension simultaneously. 3. Plasma metabolic parameters, including glucose, insulin and total cholesterol and triglyceride levels, were markedly elevated in SHRSP fatty (fa/fa) rats compared with SHRSP/Izm rats. Plasma triglyceride concentrations in SHRSP fatty (fa/fa) rats were significantly elevated compared with those in ZF (fa/fa) rats. The weight of adipose tissues in SHRSP fatty (fa/fa) rats was greater than that of SHRSP/Izm rats. The phenotype of SHRSP fatty (fa/fa) rats is similar to that of human metabolic syndrome.
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PMID:Establishment of a new animal model of metabolic syndrome: SHRSP fatty (fa/fa) rats. 1475 93

Platelet activation is involved in the pathogenesis of atherosclerosis and venous thromboembolism, and might therefore be a possible link between the two entities. Prolactin and leptin have recently been recognized as potent co-activators of ADP-dependent platelet aggregation or P-selectin expression, and are therefore suspected as additional risk factors for both arterial and venous thrombosis. There are clinical situations that have a known association with higher prolactin or leptin levels (pregnancy, obesity or anti-psychotic therapy) and increased risk of thromboembolic events. We compared the impact of both hormones on platelet activation in vitro and in vivo, indicating that prolactin has a stronger effect on platelet activation as leptin in vitro and in vivo. We have also demonstrated that prolactin levels are increased in so called idiopathic thrombosis, and that conversely, patients with prolactinoma have an increased frequency of thrombosis during the hyperprolactinemic state, in a retrospective analysis. Moreover, we have demonstrated increased prolactin values in stroke and myocardial infarction. Prospective studies have yet to be performed to give this theory its final confirmation. The involvement of hormonal factors in platelet aggregation and venous or arterial thrombosis may have important clinical implications such as for risk stratification of patients with venous and arterial thrombosis or new therapeutic options such as decreasing pro-coagulant hormone levels in certain risk situations.
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PMID:Co-activation of platelets by prolactin or leptin--pathophysiological findings and clinical implications. 1498 99


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