UMLS:C0009443 - FACTA Search

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Query: UMLS:C0009443 (cold)
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The acceleration of glycolysis by the Embden-Meyerhof pathway (EMP) in endotoxic and septic states and its counteraction by glucocorticoids has been demonstrated by past research. Although the glycolytic contribution of the hexose monophosphate (HMP) shunt is minor, its response during endotoxemia, if similar to that of EMP, could be theoretical interest, Fasted male rats (150-260 gm) were sacrificed at 5 hr after IV injection of E coli endotoxin in dosages of 2 or 3 mg/100 gm rat weight: LD50 (Nm= 15). A second group received 1 mg dexamethasone (DMS) IV per 100 gm rat weight simultaneously with endotoxin (N = 15). Livers were homogenized in 0.25 M cold sucrose and centrifuged at 15,000 g for 20 min. Specific activity of glucose-6-phosphate dehydrogenase (G6PDH) in control livers (N = 17) was 7.1 nmoles of substrate consumed per min/mg biuret protein. Endotoxin raised G6PDH activity by 49% to 10.64 units, and the endotoxin-DMS-protected group was 6.0 units. Levels of 6-phosphogluconate (6PG) were also measured in frozen liver biopsies from similar groups of rats. Liver 6PG concentrations of control (N = 15), endotoxic (N = 15), and endotoxified-DMS-treated (N = 9) groups were 22.5, 14.3, and 17.6 nmoles/gm wet tissue, respectively. The data indicate a significant 36% acceleration in 6PG consumption during endotoxemia, which is not blocked by DMS. The cofactor, nicotinamide adenine dinucleotide phosphate (NADP), decreased significantly by 18% from the control level of 152 nmoles/gm liver (N = 9) during endotoxemia, and this fall was not corrected by DMS. In a small group (N = 6), sedoheptulose-7-phosphate declined from the control value of 76 nmoles/gm wet liver by 38% after endotoxification. It is concluded that endotoxin stimulates G6PDH, the initial enzyme of the HMP pathway, and accelerates consumption of several intermediates, Glucocorticoid prevents the enzyme activity increase but does not restore 6PC and NADP concentrations to normal levels, suggesting that different enzyme sites along the HMP shunt may have unequal responses to DMS.
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PMID:Effect of endotoxin and glucocorticoid pretreatment on hexose monophosphate shunt activity in rat liver. 703 57

Amino acid enrichment of cardioplegic solutions has been shown to improve both the metabolic and functional recovery of ischemic myocardium. However, because of the marked systemic vasodilatation involved, use of amino acid enrichment is limited to the periods of induction and reperfusion. Fumarate is a Krebs' cycle intermediate whose conversion to succinate is responsible for the generation of adenosone triphosphate and the oxidation of the reduced form of nicotinamide-adenine nucleotide which is the pathway by which aspartate exerts its effect. Fumarate may also function as a free-radical scavenger and is involved in calcium transport. To determine if fumarate-enriched blood cardioplegia would improve the functional recovery of the neonatal heart, 14 neonatal piglet hearts were isolated and placed on a blood-perfused working heart circuit. After the baseline functional and metabolic assessment was done, cold ischemic arrest was initiated with either standard blood cardioplegic solution (group I; N = 7) or fumarate-enriched (13 mmol/L) blood cardioplegic solution (group II; N = 7). Cardioplegic solution was given at a pressure of 40 mm Hg every 20 minutes for 2 hours, and topical hypothermia was used. Sixty minutes after warm whole blood reperfusion, the functional recovery at left atrial pressures of 3, 6, 9, and 12 mm Hg was 70%, 66%, 66%, and 65%, respectively, in group I, versus 102%, 106%, 105%, and 109%, respectively, in group II (p < 0.05). The tissue creatinine phosphate levels after reperfusion were significantly higher in group II hearts (15.0 +/- 1.2 mumol/g dry heart tissue) than in group I hearts (9.2 +/- 1.9 mumol/g dry heart tissue), although the adenosine triphosphate levels were not significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fumarate-enriched blood cardioplegia results in complete functional recovery of immature myocardium. 801 Aug 14

Myocardial ischemia can be detected at the mitochondrial level by measuring shifts in nicotinamide adenine dinucleotide and its reduced form. Using a pulsed nitrogen laser and an optical multichannel analyzer, we monitored myocardial metabolism by measuring laser-induced nicotinamide adenine dinucleotide (reduced form) fluorescence in a large animal model of acute ischemia. Eight opened-chest sheep underwent occlusion of branches of the left anterior descending coronary artery, establishing a 15% infarct of the left ventricle. For the simulation of the clinical scenario, after 60 minutes of occlusion, the animals were supported by cardiopulmonary bypass, the aorta was crossclamped, and cold crystalloid cardioplegic solution was administered. The occlusion was removed after 10 minutes, and two additional doses of cardioplegic solution were delivered at 10-minute intervals. The aortic crossclamp was released, and a 30-minute period of reperfusion on bypass ensued. The hearts were then weaned off bypass and allowed to recover. Laser-induced fluorescence was measured inside, outside, and along the border of the infarct. Baseline measurements were made before occlusion, immediately after occlusion, and then at 5, 10, and 20 minutes after occlusion. The results show that immediately after occlusion there is a 200% +/- 30% (mean +/- standard deviation) increase in laser-induced fluorescence in the infarct zone, a 110% +/- 30% increase along the border, and no significant change in the area outside the infarct. The fluorescence in the infarct reaches a plateau in 5 minutes at 270% +/- 30%, whereas along the border it reaches a peak near end ischemia of 110% +/- 40%. With the first dose of cardioplegic solution, fluorescence increases outside the infarct and decreases inside the infarct and along the border to 120% +/- 30%, where it remains for all areas until the aortic crossclamp is removed. Fluorescence then drops to 70% +/- 20% and finally returns to baseline after 5 minutes of recovery. All of these shifts in laser-induced fluorescence were statistically significant (p < 0.01). The changes noted with doses of cardioplegic solution reflect the hypothermic and hyperkalemic effects on the myocardium. Laser-induced fluorescence provides a sensitive and specific method of monitoring myocardial ischemia during the operation. It also provides instantaneous feedback of metabolic changes that may be useful in evaluating the effects of different cardioplegic regimens and in monitoring reperfusion injury.
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PMID:Intraoperative myocardial ischemia detection with laser-induced fluorescence. 828 89

Nicotinamide-adenine-dinucleotide-specific glutamate dehydrogenase (NAD-GDH; EC 1.4.1.3) from Bacillus cereus DSM 31 was enriched 260-fold. The molecular mass was determined by gel filtration to be 270 kDa (+/- 25 kDa). The enzyme was highly specific for the coenzyme NAD(H) and catalysed both the formation and the oxidation of glutamate. Apparent Km values of 7.7 mM for glutamate and 0.56 mM for NAD+ during oxidative deamination were measured. Both in crude cell-free extracts and in enriched preparations the enzyme was extremely unstable, especially at low temperatures. The loss of activity in the cold was found to be due to the dissociation of the holoenzyme into catalytically inactive subunits of molecular mass 48 kDa (+/- 5 kDa), indicating that the native enzyme has a hexameric structure. The activity was restored under certain conditions, and no instability of the enzyme in the cold was observed in undisrupted cells.
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PMID:Properties of the cold-labile NAD(+)-specific glutamate dehydrogenase from Bacillus cereus DSM 31. 851 35

The relative effects of nicotinic acid (NA) and nitroglycerin (NT) added to cold high K+ cardioplegia were studied, to represent the two moieties of the adenosine triphosphate-sensitive potassium channel (KATP) activator nicorandil (N). In addition, we made a pooled analysis of a large series of experiments performed in our Laboratory to investigate the effects of KATP activation by N, or block (by glibenclamide, G), on postcardioplegic myocardial dysfunction. In both studies, reversibility from myocardial dysfunction (stunning) was assessed by the positive inotropic agent dobutamine. Guinea pig papillary muscle preparations were immersed in Tyrode's solution (O2 content 16 ml/l, 37 degrees C), then hypoxic (O2 content 5 ml/l) superfusion with hypothermic (20 degrees C) cardioplegic Saint Thomas' Hospital solution (STHS) was performed for 120 min. We investigated: A) 5 groups based on treatments added to STHS: 1) saline (Control (C)); 2) N = 1 mmol/L; 3) G = 1 mumol/L (also given for 15 min in Tyrode's solution); 4) NA = 1 mmol/L; 5) NT = 100 mumol/L; B) 76 consecutive experiments and we defined, independent of whether just before or during STHS: 1) KATP activation (by N, in the concentration range 1 mumol/L to 1 mmol/L, n = 36); 2) KATP block (by G 1 mumol/L, either alone or just before N, n = 20); 3) controls (n = 20) (either saline, n = 12, or saline plus dimethyl sulfoxide, as vehicle, at the ratio 100 to 1, n = 8). Absolute isometric contractility variables were evaluated along with percent changes of baseline values: 1) at 30 s of STHS, 2) after 60 min of reoxygenation with Tyrode's solution and 3) following further 15 min of dobutamine 10 mumol/L. In all preparations, developed tension (DT), time to peak tension (TPT), DT/TPT and time to arrest (TTA) were measured. In study A): TTA was significantly abbreviated (intergroup F = 5.79, p < 0.001) in N (49 +/- 11 s, mean +/- SD) p < 0.01 vs C and NA). At 30 s of STHS %DT/TPT was unchanged among groups. By contrast, after 60 min of reoxygenation %DT/TPT in N (118 +/- 35%, p < 0.05 vs C, p < 0.01 vs G) was improved (intergroup F = 5.48, p < 0.002). G, NA and NT showed recovery of contractility similar to C. However, after dobutamine the poorest %DT/TPT were seen in G (p < 0.01 vs C, p < 0.05 vs N). In study B): using the multivariate logistic model, with KATP activation, the odds of normal contractile response, respectively at 60 min of reoxygenation (t = 2.81) and after dobutamine (t = 3.22), were 29.8 and 8.86 of controls, whereas TTA (t = -1.59) was inversely related. Moreover, with KATP block the odds after dobutamine was 0.204 of controls. The relative operating characteristic plots showed areas under the curve greater than 0.7, which is evidence for accurate assessment of the predictive rules adopted. This is the first report where a probabilistic approach to cardioplegia-related experiments showed high accuracy in predicting the recovery of post-hypoxic contractile function (stunning). The results indicate that on postcardioplegic stunning: 1) KATP activation by N and KATP block by G (both given prior to or contemporary with hypoxia) have opposite effects; 2) the favorable effects of nicorandil seem unrelated to its nicotinamide or nitrose moieties.
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PMID:Activation or block of adenosine triphosphate-sensitive potassium channel have opposite effects on postcardioplegic myocardial dysfunction, "stunning". A multivariate prediction based on relative operating characteristic curve. 854 19

The purpose of this study was to assess the relationship between morphological and metabolic changes in brain edema using proton magnetic resonance systems. The serial changes during the first 24 hours in the cold-injury trauma rat brain model were investigated by proton magnetic resonance imaging (1H MRI) and high-resolution proton MR spectroscopy (1H MRS). We also analyzed the efficacy of AVS 1,2-bis (nicotinamide)-propane which can scavenge free radicals to the edema in this experiment. The edema was developing extensively via the corpus callosum in ipsi- and contralateral hemispheres as shown by gradually increased signal intensity on 1H MRI. 1H MRS initially showed accumulation of acetate and lactate, and transient increasing of glutamine. After 24 hours, the increased glutamine decreased below the control, alanine increased, and N-acetyl asparatate decreased with the edema development. AVS-treatment significantly suppressed edema development, increases of lactate and alanine and decreases of N-acetyl asparatate. We suggest that the cold-induced lesion contains anaerobic glycolysis deterioration and results in severe brain tissue breakdown. AVS is proved valuable for the treatment of this edema lesion. Clinical 1H MRS showed prolonged lactate elevation and significant decreases of other metabolites in human ischemic stroke edema. In peritumoral edema, decreased N-acetyl asparatate gradually improved, and slightly elevated lactate disappeared after tumor removal. 1H MRS feasibly characterizes the ischemic and peritumoral edema and makes a quantitative analysis in human brain metabolism. We believe the combined 1H MRI and MRS study is a practical method to monitor the brain conditions and will make it easy and possible to find new therapeutic agents to some brain disorders.
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PMID:[Sequential observations of brain edema with proton magnetic resonance imaging and spectroscopy]. 872 79

The intestinal uptake of water-soluble vitamins, nicotinamide, riboflavin, biotin and folic acid, was studied in isolated everted intestinal sleeves of the cold-water teleost rainbow trout (Onchorhynchus mykiss). The presence of a carrier-mediated transport mechanism was determined by competitive inhibition and by Michaelis-Menten kinetics. The uptake of riboflavin, biotin or folic acid was not only subject to competitive inhibition but also a saturable function of increasing vitamin concentration in the incubation medium. The kinetic constants of the saturable mechanism were for riboflavin: K(m), 2.32 +/- 0.76 microM; Vmax, 0.26 +/- 0.04 pmol/mg min; for biotin: K(m), 9.70 +/- 3.76 microM; Vmax, 0.31 +/- 0.07 pmol/mg min; and for folic acid: K(m), 32.9 +/- 21.2 microM; Vmax, 3.63 +/- 0.99 pmol/mg min. In contrast, the uptake of nicotinamide was not subject to competitive inhibition and was a linear function of concentration (Kd, 0.140 +/- 0.012 pmol/mg min microM). Folic acid was absorbed more rapidly than and was not inhibited by its derivative, 5-methyl-tetrahydrofolate. Thus, the intestinal uptake of riboflavin, biotin and folic acid is carrier-mediated while that of nicotinamide occurs by simple diffusion. These mechanisms are similar to those found in the channel catfish for the same vitamins, except for folic acid, which is absorbed by diffusion in this warm-water omnivorous species.
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PMID:Intestinal absorption of water-soluble vitamins in rainbow trout (Onchorhynchus mykiss). 910 89

In the present study, the effects of cold-water immersion on cell proliferation and nitric oxide synthase expression in the dentate gyrus of rats were investigated. Sprague-Dawley rats were divided into four groups: the control-rest group; the control-heat group; the cold-rest group; and the cold-heat group. Cold-water immersion for 5 min at 4 degrees C suppressed the numbers of 5-bromo-2'-deoxyuridine-positive and nicotinamide adenine dinucleotide phosphate-diaphorase-positive cells in the dentate gyrus, and these numbers were increased by warming for 30 min at 30 degrees C. In the present study, it was demonstrated that warming protects against cold stress-induced suppression of new cell formation, and results suggest that nitric oxide, the synthesis of which is affected adversely by cold-water immersion, may play an important role in the regulation of cell proliferation.
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PMID:Hypothermia inhibits cell proliferation and nitric oxide synthase expression in rats. 1216 Dec 61

Urinary output of water-soluble vitamins has been used as an indices for vitamin nutrition. It has been pointed out that the coefficient variance of these values is high, especially for niacin catabolites. Thus, we investigated what kinds of stress affect the catabolism using female subjects. The effects of cold exposure (as a typical physical stress), calculation exercise (a typical mental stress) and dark exposure (a typical emotional stress) on the metabolism of niacin were investigated. Of the stresses, cold exposure significantly increased urinary excretory output of the niacin metabolites. The biosynthesis of nicotinamide from Trp seemed to be increased by cold exposure.
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PMID:Effects of stress on the urinary excretory pattern of niacin catabolites, the most reliable index of niacin status, in humans. 1265 18

Umbarger, H. E. (Long Island Biological Association, Cold Spring Harbor, N.Y.), Merle A. Umbarger, and Patrick M. L. Siu. Biosynthesis of serine in Escherichia coli and Salmonella typhimurium. J. Bacteriol. 85:1431-1439. 1963.-Evidence for the operation in extracts of Escherichia coli of a pathway from glucose to serine involving 3-phosphoglycerate, phosphohydroxypyruvate, and phosphoserine as intermediates was obtained by the technique of isotopic competition. The steps of the pathway were demonstrated in extracts of E. coli and Salmonella typhimurium. The first reaction was studied in the reverse of the biosynthetic direction by observing the disappearance of reduced nicotinamide adenine dinucleotide in the presence of phosphohydroxypyruvate. The enzyme catalyzing this reaction was missing in two E. coli mutants that required serine or glycine for growth and in a representative of one of two genetically distinct classes of S. typhimurium serine-glycine auxotrophs. The second reaction, the amination of phosphohydroxypyruvate, was also studied in the reverse of the biosynthetic direction using alpha-ketoglutarate as the amino acceptor in a transamination reaction with phosphoserine. The final step, the cleavage of phosphoserine, could not be catalyzed by extracts prepared from cells of S. typhimurium serine-glycine auxotrophs of the second genetic class. It has been concluded that these three reactions provide the only significant pathway to serine in these organisms.
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PMID:BIOSYNTHESIS OF SERINE IN ESCHERICHIA COLI AND SALMONELLA TYPHIMURIUM. 1404 41

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