Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since glycogen overloading is one of the outstanding features of the diabetic liver, a series of investigations were undertaken to find an enzymatic explanation of this feature. Three groups of patients were studied: non diabetics submitted to liver biopsy during surgery (group A); non diabetics submitted to percutaneous liver biopsy (group B). In both these groups G-6-PDH, PK and MDH were assayed, all these being adaptive enzymes of intermediate metabolism. Results were expressed as muU/100 mg proteins. The significant finding of the comparison of these two groups was the low concentration of these enzymes in surgical biopsies. The depression was such that for G-6-PDH the concentration was more than 10 times less in surgical specimens as compared to percutaneous ones, whereas for PK it was almost 10 times less. In view of these findings no further surgically obtained biopsy material was used in this study. The third group (C) included insulin-dependent diabetics in good metabolic control from whom percutaneous liver biopsies were obtained for the assay of the same enzymes as above and in order to compare the results with those of group B. All three enzymes were diminished in diabetics, the difference being statistically significant for G-6-PDH and PK, not for MDH in view of the wide dispersion of the values found. Comparison and analysis of these results lead to the conclusion that in view of the low concentration of these enzymes in diabetics, glucose utilization in the liver cell must be presumed to be increased via other metabolic pathways.
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PMID:The liver in human diabetes. Concentration of some induced enzymes. 123 63

Lisinopril is a potent competitive inhibitor of purified rabbit lung ACE (dissociation t1/2 = 105 min). To examine reversibility of binding and ACE functional activity in situ, the single-pass extraction (E) of an 125I-lisinopril analogue (351A) and the hydrolysis of an ACE substrate, benz-phe-ala-pro (BPAP) were studied. Lungs were perfused at 50 ml/min with a Krebs-albumin (3%) solution. A bolus containing [14C]dextran, [3H]BPAP, and 351A was injected and (E)351A measured by multiple indicator dilution technique. BPAP metabolism (M) was reflected by the appearance of its hydrolysis product [3H]benz-phe in lung effluent. Control (E)351A was 66 +/- 5% (mean +/- SD, n = 6) and (M)BPAP was 69 +/- 9% (n = 6). Unlabeled lisinopril (30 nmol) in the bolus significantly reduced E(351A) and M(BPAP) to 16 +/- 16% and 3 +/- 3%, respectively. Ten minutes later E(351A) and M(BPAP) had returned to control values. Reduction of E(351A) was partially reversible and M(BPAP) completely reversible after 1 min. After recirculation with 0.25 mM lisinopril for 30 min, however, significant depression of E(351A) was evident for 60 min after exposure to lisinopril was discontinued. Thus, rapid as well as slowly reversible components of inhibition of ACE inhibitor binding can be demonstrated in the perfused rabbit lung.
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PMID:Rapid reversal of angiotensin converting enzyme inhibition by lisinopril in the perfused rabbit lung. 131 50

Cardiac hypertrophy is an adaptive response to an increased load imposed on the myocyte which allows the heart to perform increased work while maintaining normal myocardial fiber stress and shortening in systole. A deleterious consequence of pressure-overload hypertrophy is the prolongation of Ca(2+)-sensitive force inactivation (impaired myocardial relaxation) which is related to intrinsic alterations in cytosolic Ca2+ transport and reuptake in diastole. Additional factors appear to adversely modify myocardial relaxation in the hypertrophied heart, including the imposition of ischemia. There is also evidence that the expression and activity of the cardiac tissue renin angiotensin system (RAS) may be modified in the hypertrophied heart and contribute to diastolic dysfunction. Recent studies have demonstrated the presence of increased cardiac angiotensin converting enzyme (ACE) mRNA expression and activity in animal models of hypertrophy, including the aortic-banded rat with compensatory pressure-overload hypertrophy and rats with post-infarction remodeling. In the beating, isovolumic aortic-banded rat heart, the increased intracardiac activation of angiotensin I to II has been shown to be associated with a dose-dependent depression of diastolic relaxation. Preliminary studies suggest that the depression of diastolic function by angiotensin II in the hypertrophied heart can be prevented by the specific inhibition of cardiac ACE. In addition, the well-recognized susceptibility of the hypertrophied heart to severe ischemic diastolic dysfunction also appears to be favorably modified by the inhibition of cardiac ACE activity. The mechanisms responsible for the adverse effects of angiotensin II on diastolic relaxation in the hypertrophied heart are likely to be complex.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diastolic dysfunction in pressure-overload hypertrophy and its modification by angiotensin II: current concepts. 133 63

The effects of doxazosin (alpha-1-inhibitor) and enalapril (ACE-inhibitor) on blood pressure and exercise stress test were assessed in 10 hypertensive patients (8 M, 2 F, age 58 +/- 9 years) with coronary artery disease and exertional myocardial ischemia. A single blind, cross-over, placebo controlled trial was performed. Placebo was administered for 2 periods of 2 weeks, doxazosin and enalapril for at least 3 weeks. The sequence of the active drugs was randomized and the single daily dose, obtained by titration, was 7 +/- 5 mg for doxazosin and 18 +/- 13 mg for enalapril. Blood pressure measurements and treadmill tests (Bruce protocol) were performed at the end of each period. Rest systolic and diastolic pressures after placebo were respectively 173 +/- 15 and 106 +/- 9 mmHg and were reduced to 153 +/- 11 and 93 +/- 12 mmHg (p less than 0.05) after doxazosin and to 150 +/- 24 and 93 +/- 12 mmHg (p less than 0.05) after enalapril. Total exercise time was 473 +/- 91 s after placebo and increased to 545 +/- 84 s (p less than 0.05) after doxazosin and 529 +/- 100 s (p less than 0.05) after enalapril. Time to 1 mm ST depression (ST1) was 297 +/- 102 s after placebo and increased to 414 +/- 96 s (p less than 0.05) after doxazosin and to 396 +/- 133 s (p less than 0.05) after enalapril. Double product at peak exercise and at ST1 were respectively 26.3 +/- 2.8 and 22.1 +/- 2.8 x 10(3) and remained unchanged after enalapril and doxazosin. Peak exercise diastolic blood pressure was 107 +/- 5 mmHg after placebo, was reduced to 94 +/- 15 mmHg (p less than 0.05) after doxazosin and was unchanged after enalapril (101 +/- 10 mmHg, NS). Thus, doxazosin and enalapril induced a comparable decrease of rest blood pressure and a similar increase of exercise time in hypertensive patients with exertional myocardial ischemia. Doxazosin but not enalapril reduced exercise diastolic blood pressure.
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PMID:[Comparative effects of doxazosin and enalapril in patients with arterial hypertension and exercise-induced acute myocardial ischemia]. 168 51

In this study, the effect of bradykinin on coronary flow in the isolated rat heart was significantly potentiated when cysteine or the sulfhydryl-containing converting enzyme inhibitors captopril and zofenoprilat were administered simultaneously. In contrast, the effect of concomitant administration of enalaprilat only slightly increased the effect of bradykinin on coronary flow. In nitrate-tolerant hearts of rats pretreated with isosorbide dinitrate (15 mg daily), the increase in coronary flow by nitroglycerin and bradykinin was significantly less when compared to control hearts. The effect of captopril was not affected by pretreatment. The involvement of endothelium-derived relaxing factor (EDRF) in the effect of captopril was apparent from experiments with L-arginine, the precursor of EDRF, and L-NMMA, the "false" precursor of EDRF. L-Arginine increased the effect of captopril, whereas L-NMMA showed a competitive antagonism for the effect of captopril on coronary flow in the isolated rat heart. Clinically, the effect of captopril was studied in 10 patients with stable, exercise-induced angina pectoris that had been treated for 3 weeks with slow-release isosorbide dinitrate (20 mg four times daily). At day 7, a baseline exercise test was obtained. Subsequently, patients with chest pain and at least 1-mm ST-segment depression on the ECG during exercise were included. They received on day 14 and 21 either captopril (25 mg) or placebo 1 h before exercise testing in a randomized, double-blind, crossover design. Captopril significantly improved the combined score of maximal ST-segment depression, maximal workload, and time to angina when compared to placebo. No differences in the pressure-rate index at rest and during exercise were seen. These results indicate that the sulfhydryl group of certain angiotensin converting enzyme inhibitors can potentiate their effect on the endogenous nitrovasodilator EDRF. In the clinical situation, this may lead to an improved exercise performance in patients with stable angina pectoris during chronic nitrate treatment, independent of its systemic vascular effects.
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PMID:Converting enzyme inhibitors and the role of the sulfhydryl group in the potentiation of exo- and endogenous nitrovasodilators. 172 Aug 43

Poisoning is a significant problem in the elderly. The majority of poisonings in older people are unintentional and may result from dementia and confusion, improper use of the product, improper storage or mistaken identities. Depression is also common in the elderly and suicide attempts are more likely to be successful in this age group. The elderly patient's recuperative abilities may be inadequate as a result of numerous factors including impaired hepatic or renal function as well as chronic disease processes. General management of poisoning in the elderly parallels management of younger adults, but it is especially important to ascertain underlying medical conditions and concurrent medications. In most poisonings, activated charcoal and cathartic are sufficient. Haemodialysis or haemoperfusion may be required at lower plasma drug concentrations in elderly patients. While the specific indications for antidotes are the same for all age groups, dosage alterations and precautions may need to be considered in the elderly. Drugs most often implicated in poisonings in the elderly include psychotherapeutic drugs, cardiovascular drugs, analgesics and anti-inflammatory drugs, oral hypoglycaemics and theophylline. Cardiovascular and neurological toxicities occur with overdoses of neuroleptic drugs and, more frequently and severely, with cyclic antidepressants. Patients with pre-existing cardiovascular disease are at particular risk of worsening ischaemic heart disease and congestive heart failure. Benzodiazepines only appear to produce significant toxicity during long term administration or in combination with other CNS depressants. Digoxin can cause both chronic and acute intoxication, most seriously cardiac toxicity including severe ventricular arrhythmias, second or third degree heart block or severe refractory hyperkalaemia. Immune Fab antibody is indicated for the management of digoxin toxicity, although patients dependent on the inotropic effect of digoxin may develop heart failure after digoxin Fab antibody administration. Nitrates can cause toxicity including headache, vomiting, hypotension and tachycardia from excessive sublingual, transdermal or intravenous doses. Conduction disturbances and hypotension occur with overdoses of antihypertensive drugs; these effects are mild with angiotensin converting enzyme (ACE) inhibitors, occasionally severe with beta-blockers and of significant concern with calcium channel antagonists. The elderly commonly use aspirin and other salicylates, are more likely to develop chronic intoxications to these agents, and are more susceptible to severe complications such as pulmonary oedema. Salicylate poisoning, recognition of which is often delayed, should be considered in elderly patients with neurological abnormalities or breathing difficulties, especially in the setting of acid-base abnormalities. The clinical effects of NSAID overdose are mild and usually involve the central nervous system and gastrointestinal tract.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Poisoning in the elderly. Epidemiological, clinical and management considerations. 179 7

The aim of this study was to evaluate the anti-ischemic efficacy of 2 different doses of benazepril (B), a new ACE-inhibitor, 10 and 20 mg, given per os. Fifteen male patients gave informed, written consent; they were aged 40-67 years, with stable effort angina pectoris and were randomly given, in double-blind condition, a tablet containing B 10 mg, B 20 mg or placebo (PL), once a day, according to a 3 x 3 latin square design. Bicycle exercise tests were performed on the same day, 2 and 10 hours after the last drug intake. B 10 mg and B 20 mg, in patients with stable effort angina, compared to placebo, increased ischemic threshold and decreased ischemic ST depression at maximal work, after 2 hours but not after 10 hours. In conclusion B 10 mg and B 20 mg showed anti-ischemic activity 2 hours after drug intake.
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PMID:[Effects of benazepril, a new ACE inhibitor, in effort angina pectoris]. 179 89

1. Bradykinin (cumulative concentrations of 0.007-0.09 micrograms ml-1) produced a dose-related, but statistically insignificant depression of the isometric contraction of the isolated, spontaneously beating atria of the guinea-pig. The same concentrations of bradykinin did not change the atrial rate, but a tendency to a slight decrease was observed. 2. Enalapril (4.06 or 13.54 mumol l-1), produced a dose-related potentiation of the effect of the highest concentration of bradykinin on the isometric contraction. 3. Captopril (equimolar concentrations) also potentiated the effect of the highest concentration of bradykinin on the isometric contraction. This effect of captopril was not dose-related. 4. Both enalapril and captopril did not change the effect of bradykinin on the heart rate. 5. Bradykinin induced dose-related hypotensive responses in anaesthetized cats (0.03-1.0 microgram/kg b.w., i.v.) with a tendency towards bradycardia. 6. Enalapril (0.3 and 1.0 mg/kg b.w., i.v.) significantly potentiated bradykinin-induced hypotension and bradycardia. However, the potentiating effect of enalapril was not dose-dependent. 7. Captopril (0.1, 0.3 and 1.0 mg/kg b.w., i.v.) significantly potentiated bradykinin-induced hypotension and bradycardia. Also, the potentiating effect of captopril was not dose-dependent. 8. The failure of ACE inhibitors to potentiate the cardiodepressant and hypotensive effects of bradykinin in a dose-dependent manner is explained with some other mechanism(s) independent of ACE inhibition.
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PMID:The potentiation of cardiodepressant and hypotensive effects of bradykinin by enalapril and captopril both in vitro and in vivo. 181 Aug 15

To investigate the potential anti-ischaemic effects of benazepril (10 mg bid) in comparison to placebo, this new ACE-inhibitor was given to 11 patients with chronic stable angina, reproducible exercise-induced ST-segment depression and angiographically verified coronary artery disease. Blood pressure at rest, plasma renin activity, and plasma concentration of atrial natriuretic peptide were measured after treatment periods of two weeks. Bicycle exercise tests at the same time should evaluate ST-segment depression at comparable maximal workload, work capacity, blood pressure, and heart rate at exercise. In comparison to placebo, benazepril reduced arterial blood pressure significantly from 140 +/- 14/90 +/- 11 mm Hg to 125 +/- 16/84 +/- 10 mm Hg (p less than 0.05) and increased plasma renin activity from 2.19 +/- 3.76 ng/ml/h to 9.62 +/- 8.49 ng/ml/h (p less than 0.005). In contrast, ST-segment depression decreased only slightly and not significantly from 2.09 +/- 1.22 mm to 1.91 +/- 1.00 mm. Benazepril had neither an effect on the frequency of episodes of angina pectoris nor did it reduce the amount of GTN-consumption. Also, work capacity and plasma concentration of atrial natriuretic peptide were not changed in comparison to placebo. Although the significant reduction of blood pressure and the highly significant increase of plasma renin activity demonstrate the specific action of benazepril, a significant anti-ischaemic effect could not be established.
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PMID:[Treatment of chronic stable angina pectoris with angiotensin converting enzyme inhibition--a randomized, placebo-controlled, double-blind cross-over study]. 192 85

The effect of severe insulin-induced hypoglycemia on the activity of the pyruvate dehydrogenase enzyme complex (PDHC) was investigated in homogenates of frozen rat cerebral cortex during burst suppression EEG, after 10, 30, and 60 min of isoelectric EEG, and after 30 and 180 min and 24 h of recovery following 30 min of hypoglycemic coma. Changes in PDHC activity were correlated to levels of labile organic phosphates and glycolytic metabolites. In cortex from control animals, the rate of [1-14C]pyruvate decarboxylation was 7.1 +/- 1.3 U/mg of protein, or 35% of the total PDHC activity. The activity was unchanged during burst suppression EEG whereas the active fraction increased to 81-87% during hypoglycemic coma. Thirty minutes after glucose-induced recovery, the PDHC activity had decreased by 33% compared to control levels, and remained significantly depressed after 3 h of recovery. This decrease in activity was not due to a decrease in the total PDHC activity. At 24 h of recovery, PDHC activity had returned to control levels. We conclude that the activation of PDHC during hypoglycemic coma is probably the result of an increased PDH phosphatase activity following depolarization and calcium influx, and allosteric inhibition of PDH kinase due to increased ADP/ATP ratio. The depression of PDHC activity following hypoglycemic coma is probably due to an increased phosphorylation of the enzyme, as a consequence of an imbalance between PDH phosphatase and kinase activities. Since some reduction of the ATP/ADP ratio persisted and since the lactate/pyruvate ratio had normalized by 3 h of recovery, the depression of PDHC most likely reflects a decrease in PDH phosphatase activity, probably due to a decrease in intramitochondrial Ca2+.
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PMID:Changes in pyruvate dehydrogenase complex activity during and following severe insulin-induced hypoglycemia. 198 96


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