Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sodium 4-phenylbutyrate (4-PBA) is a low molecular weight fatty acid that has been used for treatment of urea cycle disorders in children, sickle cell disease, and thalassemia. It has been demonstrated recently that 4-PBA can act as a chemical chaperone by reducing the load of mutant or mislocated proteins retained in the endoplasmic reticulum (ER) under conditions associated with cystic fibrosis and liver injury. In the present study, we evaluated the neuroprotective effect of 4-PBA on cerebral ischemic injury. Pre- or post-treatment with 4-PBA at therapeutic doses attenuated infarction volume, hemispheric swelling, and apoptosis and improved neurological status in a mouse model of hypoxia-ischemia. Moreover, 4-PBA suppressed ER-mediated apoptosis by inhibiting eukaryotic initiation factor 2alpha phosphorylation, CCAAT/enhancer-binding protein homologous protein induction, and caspase-12 activation. In neuroblastoma neuro2a cells, 4-PBA reduced caspase-12 activation, DNA fragmentation, and cell death induced by hypoxia/reoxygenation. It protected against ER stress-induced but not mitochondria-mediated cell death. Additionally, 4-PBA inhibited the expression of inducible nitric-oxide synthase and tumor necrosis factor-alpha in primary cultured glial cells under hypoxia/reoxygenation. These results indicate that 4-PBA could protect against cerebral ischemia through inhibition of ER stress-mediated apoptosis and inflammation. Therefore, the multiple actions of 4-PBA may provide a strong effect in treatment of cerebral ischemia, and its use as a chemical chaperone would provide a novel approach for the treatment of stroke.
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PMID:Sodium 4-phenylbutyrate protects against cerebral ischemic injury. 1522 15

Ion channels are membrane proteins that flicker open and shut to regulate the flow of ions down their electrochemical gradient across the membrane and consequently regulate cellular excitability. Every living cell expresses ion channels, as they are critical life-sustaining proteins. Ion channels are generally either activated by voltage or by ligand interaction. For each group of ion channels the channels' molecular biology and biophysics will be introduced and the pharmacology of that group of channels will be reviewed. The in vitro and in vivo literature will be reviewed and, for ion channel groups in which clinical trials have been conducted, the efficacy and therapeutic potential of the neuroprotective compounds will be reviewed. A large part of this article will deal with glutamate receptors, focusing specifically on N-methyl-D-aspartate (NMDA) receptors. Although the outcome of clinical trials for NMDA receptor antagonists as therapeutics for acute stroke is disappointing, the culmination of these failed trials was preceded by a decade of efforts to develop these agents. Sodium and calcium channel antagonists will be reviewed and the newly emerging efforts to develop therapeutics targeting potassium channels will be discussed. The future development of stroke therapeutics targeting ion channels will be discussed in the context of the failures of the last decade in hopes that this decade will yield successful stroke therapeutics.
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PMID:Ion channels involved in stroke. 1599 68

Sodium MR imaging at 3.0 T provides high-quality images in acceptable acquisition times that allow assessment of tissue viability as defined by maintenance of sodium ion homeostasis. This application is made feasible for clinical stroke evaluation by an efficient projection pulse sequence with extremely short echo time values. This twisted projection imaging provides high signal-to-noise images at adequate resolution (5 x 5 x 5 mm(3)) in less than 10 minutes at 3.0 T. The images are quantified as tissue sodium concentration (TSC) maps that can be interpreted directly in terms of tissue viability. With infarction, baseline TSC values of less than 45 mmol/L increase at variable rates to approximately 70 mmol/L, allowing monitoring of the progression of stroke pathophysiology.
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PMID:Sodium MR imaging of acute and subacute stroke for assessment of tissue viability. 1636 May 94

1. Aetiological studies have shown that sodium loading increases both blood pressure and death from stroke. The present study was designed to investigate the pressor and non-pressor effects of sodium loading on stroke in stroke-prone spontaneously hypertensive rats (SHRSP). 2. Eighty-five female SHRSP were used. Forty-nine SHRSP, aged 5 months, were randomly divided into two groups with or without sodium loading and their survival times were recorded. Thirty-six SHRSP, aged 3 months, were randomly divided into two groups and were instrumented to determine blood pressure, heart period and baroreflex sensitivity (BRS) after 4 months of sodium loading or normal rat chow. After determination of BRS, blood samples were collected for the measurement of tumour necrosis factor (TNF), interleukin (IL)-1beta, IL-6 and angiotensin (Ang) II and brains were dissected for light microscopic examination. 3. Over the 15 month period, the mortality of control SHRSP was 37.5%, which reached 80.0% in the sodium loading group. Compared with the control group, blood pressure was increased but BRS was significantly decreased (P < 0.001) in sodium-loaded rats. Levels of IL-1beta, IL-6 and AngII were all significantly increased (P < 0.05) in the sodium-loaded rats. Sodium loading also markedly increased the number of cerebral aneurysms. Multivariate regression analysis showed that IL-6 was the most significant factor related to aneurysm formation. 4. Sodium loading increases death from stroke in SHRSP. The increased blood pressure, impaired BRS, inflammatory reaction and the formation of cerebral aneurysms may contribute to the development of stroke.
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PMID:Pressor and non-pressor effects of sodium loading on stroke in stroke-prone spontaneously hypertensive rats. 1804 33

Recent reports suggest that high blood pressure (BP) during the night is associated with hypertensive organ damage, and that increased BP in the morning is closely related to the incidence of stroke and ischemic heart disease. The aim of this study was to investigate the relationships between overnight urinary indicators and 24-hour (24-h) BP, especially in the morning and during sleep in the elderly. A total of 85 volunteers (males 43, females 42), aged between 51 and 76 years and not taking any antihypertensive medications, participated in this study. Their 24-h BP was measured by ambulatory BP monitoring every 30-minute using a TERUMO ES-H531 system. Overnight urine samples were collected using a proportional urine-sampling device, Urine mate P. Overnight sodium (UNa(n)) and potassium (UKn) excretions were measured by an ion electrode method. Simple linear regression analyses showed that systolic blood pressure (SBP) in the morning and diastolic blood pressure (DBP) during sleep were negatively related with overnight urinary weight standardized for body weight (UW(n)/BW). Multiple regression analyses showed that SBP during the morning and during sleep was positively related to UNa(n) and negatively related to UW(n)/BW. We also found a negative relationship between SBP during sleep and UK(n). The study suggested that urine weight adjusted for BW was negatively related with 24-h BP, especially morning BP. Sodium excretion combined with a large volume of urine proportional to body weight may prevent increases in BP, especially in the morning.
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PMID:Are overnight urinary indicators associated with morning blood pressure in the elderly? 1821 30

Sodium ion transporters in sarcolemma are involved in numerous vital cell functions, such as excitability, excitation-contraction coupling, energy metabolism, pH and volume regulation, development and growth. In a number of cardiac pathologies, the intracellular sodium concentration ([Na+]i) is elevated. Since [Na+]i and intracellular Ca2+ concentration ([Ca2+]i are coupled through the Na+/Ca(2+)-exchanger, these cardiac pathologies display disturbed calcium handling. For instance, [Na+]i is increased in heart failure (HF) leading to Na+/Ca(2+)-exchanger mediated increase in [Ca2+]i, reduced contractility and increased propensity to arrhythmias. Several studies support the contention that an increase in [Na+]i and [Ca2+]i transduces a signal the nucleus, that triggers development of cardiac remodelling and hypertrophy. Pharmacological intervention, which favourably interferes with [Na+]i and [Ca2+]i homeostasis, might prevent hypertrophy, cardiac remodelling, arrhythmias and HF. The most important sodium transport mechanisms that may underlie increased [Na+]i are: Na+/H(+)-exchanger (NHE-1), Na+-HCO(3)(-) co-transporter (NBC), Na(+)-K(+)-Cl(-) co-transporter (NKCC), Na(+)-channel, Na+/K(+)-ATPase and Na+/Ca(2+)-exchanger (NCX). Preclinical studies showed that pharmacological interventions, targeted against sarcolemmal sodium ion transporters, proved effective in ameliorating heart failure. In this respect: 1) NHE-1 inhibition reduces cardiac remodelling, hypertrophy and HF, although, in the patients following coronary artery bypass graft surgery, it was associated with an increase of stroke. 2) The activity of NBC is up-regulated, during the development of hypertrophy and may be a therapeutic strategy to prevent the development of hypertrophy and HF. 3) NKCC is increased in post-infarction HF, and the inhibition of NKCC attenuated post-infarction remodelling. 4) Inactivation of sodium channels is impaired in HF, which may result, in increased Na+ influx and prolongation of the action potential. 5) Blockade of NCX may be useful as a part of a combined therapeutic approach. Inhibition of reversed mode, or activation of forward mode NCX reduce Ca2+ overload. 6) Inhibition of Na+/K(+)-ATPase (digoxin), is used to increase contractility, however, it enhances progression of HF. Oppositely, new drugs which increase activity of Na+/K(+)-ATPase may prevent the development of cardiac remodelling hypertrophy and HF.
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PMID:Sodium ion transporters as new therapeutic targets in heart failure. 1885 35

Sodium is a required nutrient; Adequate Intakes for adults range from 1200 to 1500 mg*day(-1), depending on age. The Tolerable Upper Intake Level (UL) for sodium is 2300 mg*day(-1) for adults, based on the relationship between sodium intake and increased blood pressure. Elevated blood pressure, which is prevalent among Canadians, is, in turn, a major risk factor for stroke, cardiovascular disease, and renal disease. Sodium intake is not the only determinant of blood pressure; other modifiable risk factors include relative mass, physical activity, overall dietary quality, and alcohol consumption. However, because >90% of adult Canadian men and two thirds of Canadian women have sodium intakes above the UL, Health Canada's Working Group on Dietary Sodium Reduction has been charged with developing, implementing, and overseeing a strategy to reduce Canadians' sodium intakes. It is estimated that approximately 75% of dietary sodium is added during food processing; in addition to taste and palatability, sodium also has functional roles in food manufacturing and preservation, although the amounts used often exceed those required. Because of the central role of processed foods in sodium intake, the strategy proposed by Health Canada's Working Group includes voluntary reduction of sodium in processed foods and foods sold in food service establishments. It will also include an education and awareness campaign, and research and surveillance. Initiatives to reduce sodium in other parts of the world have demonstrated that it will be challenging to reduce sodium intake to the recommended range and will likely require many years to accomplish.
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PMID:Reducing dietary sodium intake: the Canadian context. 2013 Jun 59

Expression and transport activity of Sodium-dependent Vitamin C Transporter 2 (SVCT2) was shown in various tissues and organs. Vitamin C was shown to be cerebroprotective in several animal models of stroke. Data on expression, localization and transport activity of SVCT2 after cerebral ischemia, however, has been scarce so far. Thus, we studied the expression of SVCT2 after middle cerebral artery occlusion (MCAO) in mice by immunohistochemistry. We found an upregulation of SVCT2 after stroke. Co-stainings with Occludin, Von-Willebrand Factor and CD34 demonstrated localization of SVCT2 in brain capillary endothelial cells in the ischemic area after stroke. Time-course analyses of SVCT2 expression by immunohistochemistry and western blots showed upregulation in the subacute phase of 2-5 days. Radioactive uptake assays using (14)C-labelled ascorbic acid showed a significant increase of ascorbic acid uptake into the brain after stroke. Taken together, these results provide evidence for the expression and transport activity of SVCT2 in brain capillary endothelial cells after transient ischemia in mice. These results may lead to the development of novel neuroprotective strategies in stroke therapy.
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PMID:Sodium-dependent vitamin C transporter 2 (SVCT2) expression and activity in brain capillary endothelial cells after transient ischemia in mice. 2134 55

Sodium intake exceeds the nutritional recommendations in many industrialized countries. Excessive intake of sodium has been linked to hypertension and consequently to increased risk of stroke and premature death from cardiovascular diseases. The main source of sodium in the diet is sodium chloride. It has been established that the consumption of more than 6g NaCl/day/person is associated with an age-increase in blood pressure. Therefore, it has been recommended that the total amount of dietary salt should be maintained at about 5-6g/day. Genetically salt susceptible individuals and hypertensives would particularly benefit from low-sodium diets, the salt content of which should range between 1 and 3g/day. In industrialized countries, meat products and meat meals at home and in catering comprise one of the major sources of sodium, in the form of sodium chloride. Sodium chloride affects the flavour, texture and shelf life of meat products. The salt intake derived from meat dishes can be lowered by, whenever possible, adding the salt, not during preparation, but at the table. In most cases, salt contents of over 2% can be markedly lowered without substantial sensory deterioration or technological problems causing economical losses. Salt contents down to 1.4% NaCl in cooked sausages and 1.75% in lean meat products are enough to produce a heat stable gel with acceptable perceived saltiness as well as firmness, water-binding and fat retention. A particular problem with low-salt meat products is, however, that not only the perceived saltiness, but also the intensity of the characteristic flavour decreases. Increased meat protein content (i.e. lean meat content) in meat products reduces perceived saltiness. The required salt content for acceptable gel strength depends on the formulation of the product. When phosphates are added or the fat content is high, lower salt additions provide a more stable gel than in non-phosphate and in low-fat products. Small differences in salt content at the 2% level do not have marked effects on shelf life of the products. By using salt mixtures, usually NaCl/KCl, the intake of sodium (NaCl) can be further reduced.
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PMID:Reducing sodium intake from meat products. 2206 51

Sodium is an essential micronutrient and, via salt taste, appetitive. High consumption of sodium is, however, related to negative health effects such as hypertension, cardiovascular diseases and stroke. In industrialized countries, about 75% of sodium in the diet comes from manufactured foods and foods eaten away from home. Reducing sodium in processed foods will be, however, challenging due to sodium's specific functionality in terms of flavor and associated palatability of foods (i.e., increase of saltiness, reduction of bitterness, enhancement of sweetness and other congruent flavors). The current review discusses the sensory role of sodium in food, determinants of salt taste perception and a variety of strategies, such as sodium replacers (i.e., potassium salts) and gradual reduction of sodium, to decrease sodium in processed foods while maintaining palatability.
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PMID:Reducing sodium in foods: the effect on flavor. 2225 17


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