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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of intravenous glutamic acid infusion (3 mg/kg/min) was studied during myocardial ischemia and reperfusion in anesthetized dogs. Left ventricular ischemia was induced by underperfusion of the anterior descending and circumflex coronary arteries. Glutamic acid reduced the ischemic contractile depression 2 min after a 60%-reduction of the coronary blood flow. The left ventricular systolic pressure was decreased by 9% versus 22%, dP/dt by 16% versus 29%, left ventricular systolic pressure heart rate product by 16% versus 31%. Reperfusion with glutamic acid improved the recovery of cardiac performance without any increase in myocardial oxygen consumption. Glutamic acid infusion resulted in a 2-fold augmentation of glutamate uptake by the ischemic myocardium. It led to cessation of ammonia release by the heart due to activation of glutamine synthesis, enhancement of alanine formation coupled with pyruvate utilization and did not change lactate production. The mechanisms of the protective action of glutamic acid are discussed.
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PMID:[Correction of contractile function and metabolism in canine ischemic myocardium due to exogenous glutamic acid]. 286 92

In vivo studies were performed in the dog to verify if sodium lactate had an important effect on the metabolism of glutamine by the kidney. The animals were infused with 0.6 M sodium lactate to induce acute metabolic alkalosis with plasma bicarbonate of 29.7 mM. During these experiments, it was demonstrated that the renal uptake of glutamine increased by 46%, while the renal production of ammonia was unchanged. The renal production of alanine rose from 6.0 to 16.8 mumol/min. Plasma concentration of lactate increased from 1.3 to 19.2 mM, while that of pyruvate increased from 0.075 to 0.454 mM. In the renal tissue, alpha-ketoglutarate, malate, oxaloacetate, lactate, pyruvate, citrate, and alanine increased significantly. Similar changes were found in the liver and skeletal muscle. The observed changes are best described by transamination of pyruvate and glutamate under the influence of alanine aminotransferase (GPT). It can be calculated that this reaction was responsible for 76% of the production of ammonia from glutamine, the latter being necessary to provide glutamate for the synthesis of alanine. Dogs infused with 0.3 M sodium bicarbonate instead of sodium lactate with the same degree of acute metabolic alkalosis, showed a depression of 40% in the renal uptake of glutamine with a 38% decrease in renal ammoniagenesis and a 20% fall in the production of alanine. The present studies demonstrate that the production of ammonia from glutamine is not necessarily related to changes in acid-base balance, but may be associated with biochemical alterations related to the synthesis of alanine by the kidney.
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PMID:The metabolic response of the kidney to acute sodium lactate alkalosis. 286 25

The effect of intravenous infusion of glutamic acid on cardiac contractile function during short-term ischemia and subsequent reperfusion was studied in anaesthetized dogs. Left ventricular ischemia was induced by underperfusion of the anterior descending and circumflex coronary arteries. Infusion of glutamic acid at 3 mg/kg/min resulted in less depression of cardiac function when given after a 2 min period of 60% coronary blood flow reduction: left ventricular systolic pressure decreased by 9% vs. 22%, dP/dt decreased by 16% vs. 29%, the double product (left ventricular systolic pressure by heart rate) was reduced by 16% vs. 31%. When reperfusion was carried out during glutamic acid infusion there was a significantly enhanced recovery in cardiac function. The augmentation of cardiac performance in ischemia and reperfusion caused by glutamic acid was not accompanied by changes in myocardial oxygen consumption. Glutamic acid uptake by the ischemic myocardium increased 2-fold during infusion. This led to cessation of ammonia release from the heart due to stimulation of glutamine synthesis, and an enhancement of alanine formation coupled with pyruvate uptake but it did not effect lactate production. However, glutamic acid infusion did not influence cardiac performance and metabolism under conditions of normal coronary flow. The results suggest that elevation of glutamate arterial concentration exerts a beneficial effect on ischemic heart. The mechanisms of the protective action are discussed.
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PMID:Function and metabolism of dog heart in ischemia and in subsequent reperfusion: effect of exogenous glutamic acid. 286 19

Kinetic properties of regulatory enzymes of glycolysis in liver of the mouse, Zapus hudsonius, were modified during hibernation, the probable mechanism being covalent modification. Liver glycogen phosphorylase activity was strongly depressed during both short (less than 24 h) and long (5-8 days) term hibernation, the mechanism involving a decrease in both the percentage of enzyme in the active a form and the total amount (a + b) of enzyme expressed. Phosphofructokinase showed kinetic changes (a 2.5-fold increase in Ka for fructose-2,6-P2, 4- and 3.7-fold decreases in I50 values for ATP and citrate, compared to euthermic controls) in liver of hibernators indicative of phosphorylation inactivation of the enzyme. Measured levels of fructose-2,6-P2 in liver did not change during hibernation. Changes in pyruvate kinase kinetics in liver from long term hibernators similarly indicated enzyme phosphorylation in the depressed state (Ka for fructose-1,6-P2 increased 4.4-fold, I50 for L-alanine decreased 6.3-fold). Apparent covalent modification of glycolytic enzymes during hibernation may serve two functions: depression of glycolytic activity as part of the general metabolic rate depression of hibernation, or reorganization of fuel use in the hibernating state to limit carbohydrate catabolism and promote gluconeogenesis.
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PMID:Regulation of liver metabolism by enzyme phosphorylation during mammalian hibernation. 294 58

beta-Pyrazol-1-yl-DL-alanine, an uncommon amino acid from plants of the Cucurbitaceae, was fed to mice. Although pyrazole is known to affect the liver enzymes UDP-glucose dehydrogenase, UDP-glucuronyl transferase and UDP-glucuronic acid pyrophosphatase, and also depresses their liver glycogen concentrations, beta-pyrazol-1-ylalanine had no such effects. beta-Pyrazol-1-ylalanine could not be detected in the liver of the experimental animals but was present in the urine. No other change in urinary amino acid content was observed. Studies with [14C]-beta-pyrazol-1-yl-DL-alanine showed the administered amino acid was excreted over a 4-day period, 93% of the compound supplied was recovered. Similar recoveries were obtained with the L-enantiomer from cucumber seed. The metabolic inertness of beta-pyrazol-1-ylalanine was also apparent in experiments involving subcutaneous injection of this compound. Administration of pyrazole confirmed an earlier report of resultant increased activity of liver UDP-glucose dehydrogenase and UDP-glucuronyl transferase, and of the depression of activity of liver UDP-glucuronic acid pyrophosphatase. A concomitant 40% decrease in liver glycogen content was seen. The urine contained a novel metabolite, identified as a peptide conjugate of a pyrazole derivative. Mass spectrometry and p.m.r. spectroscopy indicate that this derivative is 3,4,4-trimethyl-5-pyrazolone. The amino acid constituents are aspartic acid, threonine, serine, glutamic acid, proline, glycine, alanine, valine and leucine. The urine of mice receiving pyrazole contained less free glycine and alanine than controls. From the results, it is concluded that pyrazole is not a catabolite of dietary beta-pyrazol-1-ylalanine but to the contrary, the amino acid is essentially excreted unchanged. Formation of 3,4,4-trimethyl-5-pyrazolone from pyrazole would imply C-methylation, a process that has not been previously observed in a mammalian detoxication context.
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PMID:Metabolism of the amino acid beta-pyrazol-1-ylalanine and its parent base pyrazole. 298 41

Single pass extraction of a new iodinated inhibitor of angiotensin-converting enzyme (ACE) was measured by means of indicator-dilution techniques applied to rabbit lungs, perfused in situ at 20 ml/min with Krebs bicarbonate solution containing 3% bovine serum albumin. A bolus containing the inhibitor, N-[1(S)-carboxy-(4-OH-3-125I-phenyl)ethyl]-L-Ala-L-Pro (CPAP), and an intravascular marker, [14C]dextran, was injected and extraction calculated at the peak of the resulting venous outflow-time curve. In 13 of 21 lungs used, a synthetic substrate for ACE, [3H]benzoyl-phenylalanyl-alanyl-proline (BPAP), was added to the bolus and appearance of its hydrolysis product, [3H]benzoyl-Phe, measured in effluent samples. When low amounts (0.15 nmol) of [125I]CPAP were injected, pulmonary extraction (E) of CPAP was 67 +/- 14% (X +/- S.D; n = 21) and metabolism (M) of BPAP was 56 +/- 9% (n = 13). Addition of unlabeled CPAP (3, 34 or 340 nmol) to the Addition of unlabeled CPAP (3, 34 or 340 nmol) to the injected bolus caused dose-dependent reduction of E(CPAP) and M(BPAP) that was no longer evident 10 min after the largest dose of CPAP. Coadministration of the ACE inhibitor, captopril (3, 6, 8 and 28 nmol), also caused dose-dependent, reversible depression of both E(CPAP) and M(BPAP). Accordingly, extraction of CPAP by perfused rabbit lung is saturable. Inasmuch as CPAP inhibits ACE activity (as reflected by BPAP metabolism) and CPAP uptake is inhibited by captopril (which also inhibits BPAP hydrolysis), it appears that a large portion of this saturable process probably reflects binding to vascular ACE.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Uptake of N-[1 (S)-carboxy-(4-OH-3-125I-phenyl)ethyl]-L-Ala-L-Pro, an inhibitor of angiotensin-converting enzyme by rabbit lungs in situ. 301 13

Since sepsis places increased demands on the host for energy and on other substrates for tissue repair and host defense, hepatic gluconeogenesis is critical for the host's adaptation to sepsis. Substrate-stimulated gluconeogenesis (i.e., gluconeogenic capacity) was assessed by the alanine load method in mannoheptulose-pretreated rats made septic by cecal ligation after laparotomy, as well as by cecal ligation and puncture after laparotomy. Fasted rats subjected to laparotomy only (sham-ligated) and fasted, nonoperated rats (controls) were investigated simultaneously. Following an overnight (-18 to 0 hr) fast, nonoperated animals converted 17.9 +/- 1.5% of [14C]alanine to [14C]glucose. Continued fasting in nonoperated animals resulted in enhanced (P less than 0.05) gluconeogenic capacity (6 hr = 27.2 +/- 3.0%; 24 hr = 26.2 +/- 1.9%; and 48 hr = 28.5 +/- 2.6%) relative to Time 0. Laparotomy alone (sham ligation) delayed the fasting-induced increase (P less than 0.05) in gluconeogenesis capacity (6 hr = 21.1 +/- 1.2%; 24 hr = 18.5 +/- 1.3%; 48 hr = 27.8 +/- 1.0%) relative to Time 0. In contrast, postoperative sepsis produced a sustained depression (P less than 0.05) of gluconeogenic capacity relative to nonoperated sham-ligated controls at 48 hr (cecal ligation, 18.4 +/- 1.4%; and cecal ligation and puncture, 18.8 +/- 1.2%). Thus, (1) fasting enhances hepatic gluconeogenic capacity; (2) surgical trauma transiently blunts the gluconeogenic response to fasting; and (3) sepsis undermines the gluconeogenic response to fasting.
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PMID:Effect of bacterial sepsis on gluconeogenic capacity in the rat. 304 7

We have evaluated the effects of dextrofenfluramine treatment on body weight control during a 90 day period, in obese patients on a calorie-restricted diet. The weight loss in dextrofenfluramine-treated patients was significantly higher than in placebo group. The rate of weight loss was linear up to the end of the trial in d-fenfluramine patients. Neural disturbances (vertigo, headache, depression) were the most frequent side effects observed in both the d-fenfluramine and in the placebo-treated groups, without significant differences between the groups. A total number of 23 patients in the dextrofenfluramine group and 20 patients in the placebo group complained side effects. Six patients (five in the d-fenfluramine group and one in the placebo group) discontinued the treatment, due to the side effects. No modifications of the biochemical parameters considered (fasting blood glucose, bilirubin, alkaline phosphatase, creatinine, blood cell counts, asparate-amino transferase (AST), alanine-amino transferase (ALT), total plasma and HDL cholesterol, and triglycerides) were observed at the end of the trial. A significant reduction of total serum cholesterol was observed in both groups at the end of the period of treatment. In conclusion, dextrafenfluramine was proved to be in short term trials an effective and safe tool in overweight control in obese patients.
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PMID:Efficacy and safety of dexfenfluramine in obese patients: a multicenter study. 305 15

Four amino acids--alanine, 2,3-diaminopropionic acid, cystine, and cystein--and also one diamine, ethylenediamine, were chelated with 99m-technetium (99mTc), and their renal excretion patterns were studied in rabbits in the presence and absence of two renal tubular transport inhibitors, probenecid and 2,4-dinitrophenol. From the depression of renal excretion for the first three amino acid chelates, in the presence of the inhibitors, a renal tubular excretory pathway of elimination was suggested for these compounds. The renal excretions of 99mTc-cystein and 99mTc-ethylenediamine however, remained undepressed under similar experimental conditions. An explanation of these observations was forwarded from the possible chemical structures of these chelates.
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PMID:Renal handling of amino acid 99mtechnetium chelates. 321

After 10 mg nicardipine IV a patient with stable angina developed chest pain and ST-segment depression accompanied by excessive tachycardia, low arterial blood pressure, and initially decreased coronary sinus blood flow. Measurements of arterial concentrations and cardiac exchanges of lactate, glucose, free fatty acids, glutamate, and alanine showed alterations indicative of severe ischemia.
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PMID:Hemodynamic and cardiac metabolic changes during nicardipine-induced myocardial ischemia. 334 16


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