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)

Recent studies suggest that serotonergic receptor activation is coupled to phospholipase C-mediated phosphoinositide hydrolysis, which results in the release of intracellular second messengers. The purpose of this study was to determine whether altered phosphoinositide metabolism is the basis for augmented vascular responsiveness to serotonin in genetic hypertension. Thoracic aortic segments isolated from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto normotensive rats (WKY) were labeled with myo-[3H]inositol and stimulated with serotonin in the presence of LiCl. Accumulation of [3H]inositol phosphates was then quantitated by column chromatography. Basal inositol phosphate accumulation and basal incorporation of myo-[3H]inositol into aortic cell membranes from SHRSP was not significantly different from WKY values. At 2.6 x 10(-7) to 2.6 x 10(-4) M serotonin, phosphoinositide metabolism was significantly augmented in aortae from SHRSP compared with WKY. Depolarization (100 mM KCl) did not increase phosphoinositide hydrolysis above basal levels in SHRSP or WKY. 2-Nitro-4-carboxyphenyl-N,N-diphenyl carbamate (NCDC), an inhibitor of phospholipase C, prevented the serotonin-induced phosphoinositide metabolism. NCDC also partially inhibited phasic contractions (responses in calcium-free solution) to serotonin in aortas from SHRSP and WKY. In conclusion, abnormal phosphoinositide metabolism may be one mechanism responsible for the characteristic increase in vascular reactivity to serotonin in hypertension.
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PMID:Augmented phosphoinositide metabolism in aortas from genetically hypertensive rats. 215 30

Iliac crest bone histomorphometry, plasma and urine biochemistry and clinical history were examined in 78 unselected patients (68 women, 10 men) at the time of femoral fracture. Histological abnormalities occurred in 56 of the 78 biopsies. The commonest of these was a low bone volume of less than 15% which, irrespective of other abnormal histological features, was present in 37 of the biopsies. On the basis of the histomorphometry, patients could be classified into four main groups. Normal histomorphometry (bone volume greater than 15%, osteoid surfaces less than 24%, mineralising surface greater than 60%) was present in 22 patients, 23 had osteoporosis as the only abnormality (bone volume less than 15%, osteoid surface less than 24%, mineralising surface greater than 60%), nine had osteomalacia (osteoid surfaces greater than 24%, mineralising surface less than 60%, osteoid width greater than 13 microns) and 13 had decreased mineralising surfaces. Of the remainder, five had increased osteoid surface and six had insufficient osteoid to assess mineralising surface. Plasma and urine biochemistry in the four groups showed that, compared to age-matched controls, all groups had reduced plasma albumin. In comparison to the group with normal histomorphometry, patients with osteoporosis had a higher plasma calcium (P less than 0.01), tubular reabsorption of calcium (P less than 0.05) and plasma vitamin D binding protein (P less than 0.01); patients with osteomalacia had a higher plasma creatinine (P less than 0.02) and parathyroid hormone (P less than 0.02) and lower plasma 24,25-dihydroxyvitamin D (P less than 0.02), urinary calcium/creatinine ratio (P less than 0.02) and tubular reabsorption of phosphate (P less than 0.02). The biochemistry in patients with decreased mineralising surface was no different from patients with a normal biopsy. The prevalence of both osteoporosis and osteomalacia increased with age and, in subjects over the age of 90, osteoporosis occurred in 71% of patients and osteomalacia occurred in 29% of patients. The osteomalacic group were significantly older than the other three groups (P less than 0.05). The histomorphometry did not relate to the site of fracture (subcapital or intertrochanteric). A history of stroke, gastrectomy, rheumatoid arthritis, steroid treatment, thyroid disease, alcohol abuse and anti-convulsant therapy was present in patients with femoral fracture but did not relate to any particular histomorphometric classification.
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PMID:Osteomalacia and osteoporosis in femoral neck fracture. 226 50

High concentrations of adrenergic agonists are known to cause significant structural damage to the heart, accompanied by depressed cardiac performance. These studies were undertaken to further elucidate mechanisms that contribute to this process. Rabbits were infused with either norepinephrine (NE, 3 micrograms.min-1.kg-1 iv) for 90 min or with an equivalent volume of normal saline (controls). The heart was immediately extracted and studied as an isolated working heart preparation perfused with erythrocyte-enhanced buffer. Stroke work, coronary flow, and O2 metabolism were determined, and substrate oxidation was measured by [14C]glucose or palmitate. Stroke work performed by hearts exposed to NE was only 31% of controls (2.6 +/- 0.4 vs. 8.4 +/- 0.9 g.cm-1.g-1). This was matched by reductions in coronary flow and O2 metabolism. Glucose oxidation was reduced from 54.6 +/- 3.9 to 16.0 +/- 5.3 nmol.min-1.g-1, and palmitate oxidation from 49.8 +/- 5.3 to 21.0 +/- 4.1 nmol.min-1.g-1 in the NE group. However, ATP, creatine phosphate, glycogen, and triacylglycerol concentrations were identical with the control group. O2 delivery per unit substrate oxidation was not lower in the NE group, and O2 extraction did not differ significantly. These findings indicate that the markedly lower contractile performance of the hearts exposed to NE cannot be attributed to a deficiency of metabolic capacity or limitation of O2 or substrate availability because of vasospasm. In view of the brief time (90 min), it is unlikely that leukocyte accumulation was a major factor. The observations are consistent with NE-derived oxidant injury, possibly causing disordered excitation-contraction coupling.
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PMID:Preservation of cardiac metabolic capacity after acute catecholamine injury. 230

Phosphate has been proposed as an ergogenic aid since it may enhance O2 delivery and cardiac work efficiency by increasing plasma phosphate (P Pi), red blood cell phosphate (RBC Pi), 2,3-diphosphoglycerate (DPG), RBC adenosine triphosphate (ATP), and P50. In 10 normal, fasting males we measured cardiac output (Q) by CO2 rebreathing, heart rate (HR), O2 deficit (O2DEF), and O2 consumption (VO2) during cycle ergometer exercise (60% of peak VO2). Stroke volume (SV) and arteriovenous O2 difference (A-VO2) were calculated. Following a baseline blood sample (BASE) for P Pi, RBC Pi, DPG, RBC ATP, and P50 (3 h before exercise), a single oral dose of dicalcium phosphate (129 mmol) and glucose (500 ml/10% sol, PHOS), or placebo (PLA), was administered in a random, crossover, double-blind fashion. Blood sampling was repeated immediately before and after exercise (PRE-EX and POST-EX). PHOS induced increases in P Pi (3.87 to 4.35 mg.dl-1, P less than 0.05), RBC Pi (3.86 to 4.63 mg.dl-1, P = 0.08), DPG (11.8 to 13.1 mumol.g-1 Hb, P less than 0.05), RBC ATP (4.2 to 4.4 mumol.g-1 Hb, P less than 0.05), and P50 (26.8 to 27.9 mm Hg, P less than 0.05) from BASE to PRE-EX. All variables remained elevated through the exercise period, as evidenced by higher levels than BASE at POST-EX (P less than 0.05). However, P50 was not different across conditions at PRE-EX (PHOS P50 = 27.9, PLA P50 = 28.3 mm Hg) or POST-EX (PHOS P50 = 28.0, PLA P50 = 28.1 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxygen delivery and cardiac output during exercise following oral phosphate-glucose. 238 2

The energy metabolism of the brain was measured in three types of ischemic models in the cat using phosphorus-31 magnetic resonance spectroscopy. The cerebral ischemia was produced as follows. In Group 1, two balloons were inflated in the left subclavian artery and the brachiocephalic trunk. In Group 2, the left middle cerebral artery was occluded through a transorbital approach. A combination of the two was employed in Group 3. Phosphorus-31 magnetic resonance spectra were obtained serially during 2 hours of ischemia. Immediately after occlusion, peaks of phosphocreatine and adenosine triphosphate decreased, whereas the peak of inorganic phosphate increased and split in two. Intracellular pH determined by chemical shift of the inorganic phosphate peak decreased. These changes were more pronounced in Group 3 when compared with the other groups. Histological study showed no infarction in Group 1 and infarcted areas in Groups 2 and 3. The size of the infarcted area in Group 3 was larger than that in Group 2. These results suggest that the model of middle cerebral artery occlusion potentiated with the occlusion of the brachiocephalic trunk and the left subclavian artery by balloon catheters is a reliable stroke model and that phosphorus-31 magnetic resonance spectroscopy is useful to understand the pathophysiological state of cerebral ischemia in vivo.
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PMID:Phosphorus-31 magnetic resonance spectroscopy of cerebral ischemia in cats. 238 42

In vivo 31-Phosphorus nuclear magnetic resonance (31PNMR) spectroscopy was used to study regional high energy phosphate, and phospholipid metabolism together with intracellular pH in patients with acute hemispheric ischemic stroke. The pH of ischemic brain progressed from acidosis to alkalosis. Acidosis was correlated with metabolic deterioration. Alkalosis was correlated with poor neurological outcome. Hyperglycemia worsened acidosis and metabolic breakdown. Therapeutic control of systemic glucose levels and cerebral acidosis should be evaluated in acute stroke.
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PMID:Pathophysiological correlates of cerebral ischemia the significance of cellular acid base shifts. 240 27

A hair seeding technique has been developed to obtain diffraction quality crystals of yeast (Saccharomyces cerevisiae) iso-2-cytochrome c, a model for studies of protein folding and biological electron transfer reactions. Deep red crystals of this protein were obtained from 88 to 92% saturated solutions of ammonium sulfate containing 20 mg protein/ml, 0.1 M-sodium phoshate, 0.3 M-sodium chloride, 0.04 M-dithiothreitol and adjusted to phosphate, 0.3 M-sodium chloride, 0.04 M-dithiothreitol and adjusted to pH 6.0. Rapid crystal growth was observed, but only along the path of the seeding hair stroke. The space group is P4(3)2(1)2 (or P4(1)2(1)2) with a = b = 36.4 A, c = 137.8 A (1 A = 0.1 nm) and Z = 8. Crystals are stable in the X-ray beam for more than 10 days and diffract to at least 2.5 A resolution. The same hair seeding methodology has proven useful in obtaining crystals of specifically designed mutant iso-2 proteins and in other protein systems where consistent crystal growth had previously proven difficult to attain.
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PMID:Crystallization of yeast iso-2-cytochrome c using a novel hair seeding technique. 254 32

Image-guided 31P and 1H magnetic resonance localized spectroscopy was performed on patients with brain tumors, temporal lobe epilepsy, chronic brain stroke, and deep white matter lesions. Absolute molar concentrations of metabolites, peak area ratios, and pH were obtained. The important findings were that 31P metabolite concentrations were significantly reduced in tumors, infarcts, and deep white matter lesions. Similarly, 1H metabolite intensities were reduced in chronic stroke. In the seizure foci of epilepsy patients, in tumors, and in chronic stroke, the pH was more alkaline than the normal pH. Peak area ratios were altered in tumors (reduction of phosphocreatine/inorganic phosphate (PCr/Pi) and in chronic stroke (large increases in Cr/NAA and Cho/NAA). Finally, the spectroscopic imaging technique offers a versatile alternative to the "single point" techniques, producing spectra or images of the spatial distribution of individual 31P metabolites.
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PMID:Clinical MRS studies of the brain. 255 86

An analysis of steady-state kinetics of purified rat liver transketolase shows that the reaction proceeds according to a two-stroke substitution ("ping-pong") mechanism. Based on the kinetic data, a competitive relationship was shown to exist between xylulose-5-phosphate and ribose-5-phosphate for the sites of substrate binding by the substituted form of the enzyme with the formation of a non-productive abortive complex (kd = 125 microM). The values of constants of two monomolecular steps of the reaction (k2 = 42 s-1; k4 = 9.4 s-1) were determined. It was assumed that the maximum rate-limiting step of the transketolase reaction is the degradation of the substituted form of transketolase--ribose-5-phosphate complex having a rate constant of k4.
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PMID:[Kinetic properties of transketolase from the rat liver in a reaction with xylulose-5-phosphate and ribose-5-phosphate]. 263 2

Myocardial function with ultrastructure and high energy phosphate levels in dogs was correlated after 24 hours of sepsis using live Klebsiella aerogenes. All animals developed progressive hemodynamic deterioration over a 24 hour period. Mean arterial pressure decreased from 148 +/- 7 mmHg to 85 (P less than 0.01) and cardiac output decreased from 3.43 +/- .31 to 1.6 +/- 0.5 L/min. Left ventricular stroke work decreased from 48.2 +/- 5 to 18.1 +/- 6 gm-meters (P less than 0.001). Systemic and pulmonary vascular resistances were increased at 24 hours (3,538 +/- 27 to 7,404 +/- 1,400 dyne/sec/cm-5 (P less than 0.01), and 185 +/- 20 and 619 +/- 90 dyne/sec/cm-5 (P less than 0.001), respectively. Left ventricular function curves at 24 hours showed a fixed low output. However, myocardial ultrastructure was preserved and high energy phosphate levels remained normal. These observations correlate well with the changes seen clinically in early gram negative sepsis in hypovolemic patients. Thus, this appears to be a suitable model for further investigation of the effects of gram negative sepsis on myocardial performance, ultrastructure, and maintenance of energy stores.
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PMID:Preservation of myocardial ultrastructure after 24 hours of Klebsiella sepsis: histologic, functional, and biochemical correlations. 268 98


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