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)

Alcohol has at least two actions on essential fatty acid (EFA) and Prostaglandin (PG) metabolism. It enhances the conversion of dihomogammalinolenic acid (DGLA) to PGE1 but it blocks the activity of the delta-6-desaturase, an enzyme necessary for replenishment of DGLA stores from dietary precursors. The acute effect of ethanol is therefore an increased production of PGE1 but chronic consumption will lead to depletion of DGLA and PGE1. Withdrawal from alcohol will lead to a precipitous fall in PGE1. PGE1 is known to have profound effects on the nervous system and behaviour. Patients with mania produce more PGE1 than normal while those with depression make less. Alcoholics may drink to maintain a normal PGE1 level, something which will require more and more ethanol as DGLA is depleted. In both animals and humans PGE1 or its precursor, gamma-linolenic acid (GLA) have been shown to attenuate the acute withdrawal syndrome. PGE1 injections prevent the development of fatty liver in alcohol-treated animals. Defective EFA and PGE1 metabolism are known to lead to increased fibrosis, reproductive failure, cardiomyopathy, cardiovascular disorders, gastritis and pancreatitis and could therefore be the basis for these disorders in alcoholics. A PGE1 deficiency could also be responsible for the fetal alcohol syndrome. Three other agents are known to produce constellations of fetal defects very similar to those found in the alcohol syndrome. These other factors are dihphenylhydantoin, lithium, and a deficiency of zinc. These three factors and excessive alcohol consumption all lead to PGE1 deficiency by different routes. If this concept is correct, the key to the management of alcoholism and its medical complications lies in the provision of GLA or DGLA, fatty acids which by-pass the alcohol blocked step and which are unfortunately unlikely to be present in any normal diet. Unlike many concepts of alcoholism and alcohol damage, the EFA/PGE1 idea is very readily testable and already has considerable experimental support.
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PMID:A biochemical basis for alcoholism and alcohol-induced damage including the fetal alcohol syndrome and cirrhosis: interference with essential fatty acid and prostaglandin metabolism. 625 73

Studies on the rats with genetically-controlled hypertension (spontaneously hypertensive rats, SHR) in which myocardiopathy had been produced by isoproterenol (ISP) administration (2 X 80 mg/kg sc daily for two days) have shown that the myocardiopathy results in a fall of the activity of adenylate cyclase (AC) lasting from the second to the fourth day after administration of ISP, while the activity of phosphodiesterase (PDE) remained unchanged. In vitro, ISP (10(-7)-10(-4)M), Mg2+ (4-25nM), GTP (10(-6)-10(-5)M) and GTP (10(-5)M) given in combination with ISP (10(-6)-10(-5)M) elevated the AC activity in the cardiac muscle of SHR similarly in controls and the rats with ISP-induced myocardiopathy. The results indicate that the depression of AC activity in the cardiac muscle of SHR following ISP-induced myocardiopathy is a result of reduction of the number of AC molecules rather than a consequence of the structural damage of AC.
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PMID:The activity of adenylate cyclase and phosphodiesterase in the isoproterenol-damaged cardiac muscle of spontaneously hypertensive rats. 631 39

Summarizing some essential results from empirical investigations about the individual adaptation and coping with coronary heart diseases five principles are formulated: It ist not possible to predict the individual reactions to a coronary disease from the knowledge of the pathophysiological aspects. The behaviour pattern of these patients are different and complex determined. The individual reactions to the outbreak of the disease equally depend on familial, occupational, social and public health care factors on one side and on intrapsychical factors of the patient on the other side (i.e. personality structure, psychological status before the event etc.). The fact of a coronary or myocardial disease does not necessarily lead to a life-crisis or maladaptation. For the patient's style of life positive and/or negative effects of the disease can be differentiated. The patient's appraisal of a therapeutic success depends therefore on the intraindividual reinforcement-value of such a success. Adaptation and coping strategies are not uniform in phenomenological or time aspects. The emotional, cognitive and behavioural patterns primarily tend to help to cope with anxiety and uncertainty (f.i. denial, depression, aggression, building up a new identity). In the patient's mind a myocardial infarction is not necessarily the most important event in his actual life-situation. Concerning the heart disease fears about the own capacity of work and financial outcome are dominant. They are followed by concerns about the medical prognosis or course of disease, family life and partnership, satisfaction with future life and its meaning, and aspects of the social or ecological environment. Over all these patients show relatively optimistic prospects to their own future.
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PMID:[Psychological adaptation in coronary patients]. 649 49

Male weanling rats were made copper deficient with a purified diet containing all known essential dietary nutrients except copper. Copper deficiency was verified by indirect (anemia, growth retardation, hypercholesterolemia, gross pathology, and abnormal electrocardiograms) and direct (tissue copper analysis) criteria. His bundle electrographic and electrocardiographic changes detected in the copper-deficient group consisted most notably of depressed His-Purkinje system conductivity and S-T segment depression. Phosphorus-31 nuclear magnetic resonance spectroscopic analysis of cardiac, renal, and hepatic tissue perchloric acid extracts revealed significant metabolic changes associated with the dietary copper deficiency, including a generalized marked decrease in ATP and phosphocreatine levels and a corresponding increase in inorganic orthophosphate and ADP levels in the various tissues. Tissue-specific changes consisting of elevated ribose 5-phosphate (heart), phosphocholine (heart), and inosine monophosphate (kidney) and decreased glycerol 3-phosphorylethanolamine (liver) and glycerol 3-phosphorylcholine (liver) levels were detected in copper-deficient rats. Microscopic examination of heart tissue from copper-deficient rats revealed extensive disruption of mitochondrial fine structure, including fragmentation of cristae and inner and outer mitochondrial membranes, which resulted in pronounced vacuolization throughout the tissue. Although the physiological and metabolic disturbances manifested in hearts from copper-deficient animals generally mimic myocardial responses to chronic ischemia, the observed changes are interpreted in a broader context to represent the appearance of a copper-dependent cardiomyopathy.
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PMID:Physiological and metabolic characterization of a cardiomyopathy induced by chronic copper deficiency. 663 5

The exercise test in 30 patients with hypertrophic (HCM) and 29 patients with dilatative cardiomoyopathy (DCM) showed a positive test with significant ST depression in half of each group. In 12 out of 30 patients with HCM and 7 out of 29 patients with DCM, exercise testing caused angina. Rhythm disturbances surprisingly did not occur in HCM but where unexpectedly frequent in DCM: in 4 cases exercise testing provoked frequent supraventricular premature beats, in 3 patients paroxysmal atrial fibrillation, and in 11 patients ventricular ectopic beats (Lown class II-IVb). Nine patients exhibited an exacerbation by at least one Lown class as compared with the electrocardiogram at rest. In patients with atypical angina pectoris and a pathological exercise test the possibility of cardiomyopathy - apart from coronary artery disease - should be increasingly considered. With provocation of arrhythmias the possibility of DCM should especially be borne in mind.
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PMID:[The exercise test in cardiomyopathy]. 668 38

The purpose of this study was to determine whether an exercise-induced decrease in ejection fraction in patients with coronary artery disease and left ventricular dysfunction at rest represents ischemia or the nonspecific response of a compromised left ventricle to exercise stress. Accordingly, radionuclide ejection fraction responses of 246 patients with coronary artery disease and an ejection fraction at rest of less than 0.50 were compared with those of a "nonischemic" control group of 48 patients with idiopathic dilated cardiomyopathy and a similar degree of ventricular dysfunction. The significance of the ejection fraction response in the group with coronary artery disease was further examined by relating it to the angiographic extent of coronary artery disease, severity of angina, incidence of chest pain and electrocardiographic ST segment depression during exercise and long-term prognosis. The ejection fraction decreased by greater than or equal to 0.01 and greater than or equal to 0.05 during exercise in 48 and 28%, respectively, of the patients with coronary artery disease compared with only 8 and 2%, respectively, of the patients with cardiomyopathy. When exercise was limited by fatigue at a submaximal heart rate, the ejection fraction decreased in 25% of the patients with coronary artery disease but in none of the patients with cardiomyopathy. Patients with coronary artery disease whose ejection fraction decreased during exercise had a significantly higher incidence of three vessel disease, exercise-induced chest pain or ST depression and late mortality than did patients whose ejection fraction did not decrease. These relations were confirmed equally in subgroups of patients with moderate (ejection fraction 0.30 to 0.49) and severe (ejection fraction less than 0.30) left ventricular dysfunction. Thus, in patients with coronary artery disease and left ventricular dysfunction at rest, a decrease in ejection fraction during exercise is more likely to indicate ischemia than a nonspecific left ventricular response to exercise stress. In the individual patient, a decrease of 0.05 or greater, or a decrease during submaximal exercise, appears to be highly specific for ischemia. A decrease in ejection fraction identifies a subgroup of patients with a high prevalence of multivessel coronary artery disease and a high risk of death during long-term follow-up on medical therapy.
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PMID:Mechanism and significance of a decrease in ejection fraction during exercise in patients with coronary artery disease and left ventricular dysfunction at rest. 669 May 59

The effects of ethanol and acetaldehyde on basal tension of canine small and large coronary arteries were examined in vitro. Ethanol in a concentration as little as 8.5 mM can induce threshold contractions of coronary arteries. High concentrations of ethanol produce concentration-dependent coronary vasospasms equivalent to those induced by supra-maximal concentrations of KCl. Acetaldehyde (10(-5) to 10(-2)M) resulted in concentration-dependent relaxation of basal tone. Use of a variety of pharmacological antagonists (i.e., phentolamine, methysergide, diphenhydramine, metiamide, propranolol and indomethacin) did not attenuate or prevent the spasmogenic actions of ethanol. These findings could help to explain why alcohol can induce cardiac depression, arrhythmias, cardiomyopathy and the higher than normal incidence of sudden death observed in 'binge' drinkers.
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PMID:Ethanol produces coronary vasospasm: evidence for a direct action of ethanol on vascular muscle. 683 Nov 12

To study right ventricular function, we performed cardiac catheterization, and right and left cineventriculograms in 60 chagasic patients and 15 non-chagasic, non-heart disease patients. Chagasic patients with normal electrocardiograms and left cineventriculograms also had normal right ventricular function. Nine of 14 chagasic patients with normal Ecg's and early left ventricular damage had right ventricular dilatation and/or segmental inferior-apical asynergy. Fourteen of 19 chagasic patients with abnormal Ecg's and advanced left ventricular damage, but without signs of congestive heart failure, and all chagasic patients with congestive heart failure, had marked right ventricular dilatation, severe right contractility depression and abnormal right apical or para-apical motion. These findings indicate that Chagas disease is a diffuse cardiomyopathy in which the left ventricle seems to be affected earlier and to a greater extent than the right ventricle. Since segmental abnormalities were predominantly observed in apical and para-apical areas of the ventricles, performance of right and left cineventriculograms is recommended before implantation of cardiac pacemakers.
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PMID:Right ventricular function in Chagas disease. 684 Sep 1

A clinical syndrome of severe cardiomyopathy often accompanies administration of high doses of anthracycline agents. We studied 36 patients serially with radionuclide angiography. At three weeks following drug administration, 8 of 36 patients showed depression of ejection fraction (EF). All had received at least 280 mg/m2 of the drug and 7 had received more than 380 mg/M2. Definite clinical syndromes of congestive cardiomyopathy developed only in patients showing EF depression and in some patients, EF depression developed without signs of congestive heart failure. Ejection fraction studies at 5 minutes, 1 hour, 4 hours, 24 hours, 72 hours, and one week following drug administration showed no changes when compared to immediate preg-drug EF. Seven patients who died during the study underwent histologic examination. Only the single patient with a depressed EF showed histologic evidence of athracycline cardiotoxicity, although all but 1 of these patients had received at least 400 mg/M2. We conclude that serial radionuclide EF just prior to anthracycline administration is a potentially useful predictor of cardiac toxicity, and that EF depression and/or preservation of a normal EF should be weighed in the decision for administering a drug of this type at high dosage levels.
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PMID:Anthracycline cardiotoxicity: clinical and pathologic outcomes assessed by radionuclide ejection fraction. 693 1

Diabetes appears to cause a cardiomyopathy independent of atherosclerotic coronary artery disease and hypertension. Left ventricular papillary muscle function studies in rats made severely diabetic with streptozotocin have shown a slowing of relaxation and a depression of shortening velocity. However, the effects of insulin therapy on the myocardial mechanics of diabetic rats have not been studied. Therefore, rats diabetic for 6-10 weeks were treated with PZI insulin for 2, 6, 10, or 28 days and the mechanical performance of their left ventricular papillary muscles was compared to that of untreated diabetics and age-matched controls; cardiac contractile protein enzymatic activity was also measured. Neither 2 nor 6 days of therapy had any effects on the depressed cardiac muscle performance of diabetic animals, although plasma glucose concentration was restored to normal. By 10 days of therapy, recovery of mechanical performance was nearly complete, and by 28 days of therapy, complete reversal of the altered myocardial mechanics was observed. Crystalline insulin added to the bath (9 mU/ml) had no effect on myocardial mechanics in either diabetics or controls. A gradual recovery of actomyosin and myosin ATPase activity in the hearts of insulin-treated diabetic animals was also found, complementing the mechanical studies. In addition to demonstrating a gradual but complete reversibility of the abnormalities in papillary muscle function in diabetic rats (although control of hyperglycemia was less than ideal), this study confirms that this model of a cardiomyopathy is not a result of streptozotocin-induced cardiac toxicity. Additional data are provided indicating that depressed thyroid hormone levels in diabetic rats are not responsible for the mechanical changes observed.
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PMID:Reversibility of diabetic cardiomyopathy with insulin in rats. 703 May 13


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