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)

It was discovered that the product of a mix containing the enzyme creatine phosphokinase (CPK) and either glutathione (GSH) or cysteine caused platelets to adhere together in vitro. This platelet adhesive factor (PAF) was formed as CPK enzyme activity declined. An alternative method for the destruction of enzyme activity--heat at 56 degrees C--also resulted in the formation of an in-vitro active PAF which was both less stable and active than its chemically produced counterpart. Assay of the platelet adhesive potency of the CPK-GSH mix, using human platelets, revealed a wide variation in the response of different individuals' platelets to standard quantities of PAF. The nature of this preparation of PAF was investigated by both biochemical and biophysical means, including ion exchange chromatography, electrophoresis, amino acid analysis and analytical ultracentrifuge studies. Evidence is presented that PAF is the product of the disruption of the dimeric structure of the CPK molecule. PAF was found to adhere to paper, under the conditions of electrophoresis imposed, and also to cause sephadex beads to bind together, characteristics which suggested that the platelet adhesion reaction was probably a biophysical process. Red and white cells were not similarly affected. The feasibility of this novel concept for the initiation of platelet adhesion, as a naturally occurring process, was supported by the results of animal experiments in which a statistically depression of platelets in the systemic circulation followed the intravascular administration of PAF. The possible relevance to man of this basic mechanism in relation to exercise and disease processes, including ideopathic and post-traumatic thrombosis, atherogenesis, and dysbaric aseptic necrosis of bone, is discussed.
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PMID:The formation of a platelet adhesive factor by disruption of the creatine phosphokinase molecule. 1 Mar 63

Components of the complement system are known to play an important role in the cytolytic process and in chemotaxis of leukocytes. Cobra venom factor specifically cleaves C3 activity via activation of the alternative (properdin) complement pathway. It does not act directly on C3. If C3 is involved in tissue necrosis after ischemic injury, cobra venom factor might reduce tissue damage after acute coronary occlusion. Accordingly, in 14 control dogs occlusion of the left anterior descending artery was carried out for 24 h. Epicardial electrograms were recorded 15 min after occlusion, and 24 h later transmural specimens for creatine phosphokinase activity (CPK) and for histological analysis were obtained from the same sites. In another 14 experimental dogs, 20 U/kg cobra venom factor was given intravenously 30 min after occlusion. Serum complement levels fell within 2-4 h to <20% of normal. In the control dogs, the relationship between ST-segment elevation and CPK activity 24 h later was: log CPK = -0.06 ST + 1.48 (n = 111 specimens, 14 dogs, r = 0.77). In the experimental dogs, log CPK = -0.024 ST + 1.46 (n = 111 specimens, 14 dogs, r = 0.60), showing significantly different slopes (P < 0.001), i.e., less CPK depression for any level of ST-segment elevation. Histologically, 69 of 71 sites (97%) with ST-segment elevation exceeding 2 mV in the control dogs showed signs of necrosis 24 h later, whereas in the experimental group only 43 of 79 sites (54%) with abnormal ST-segment elevations showed signs of necrosis (P < 0.0005). At the same time, it was shown that the administration of cobra venom factor did not alter cardiac performance, collateral blood flow to the ischemic myocardium or the clotting system, but infiltration of polymorphonuclear leukocytes into the myocardium was decreased. It is concluded that cobra venom factor, by reducing the amount of C3 and C5 substrate available for chemotactic factor generation, or other as yet undefined mechanisms, protects the ischemic myocardium from undergoing necrosis, as judged by histology and local CPK activity. Hence, a new approach to limiting the extent of myocardial infarcts after experimental coronary occlusion, based upon inhibition of complement-dependent inflammatory processes, is demonstrated.
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PMID:Reduction by cobra venom factor of myocardial necrosis after coronary artery occlusion. 64 Nov 47

The goal of this study was to determine if changes in the epicardial QRS complex after coronary artery occlusion (CAO) can be used to evaluate the efficacy of interventions designed to limit infarct size. Forty-one open-chest dogs with CAO were studied: 15 were controls, 18 received hyaluronidase and eight received propranolol starting 20 minutes after CAO. Epicardial ECGs were recorded at specific time intervals to analyze ST-segment elevation and changes in Q and R waves. Transmural specimens were obtained 24 hours after CAO from the same sites at which ECGs were recorded. Q wave development (deltaQ), R wave fall (deltaR), and their combination (deltaR + deltaQ) at 24 hours correlated with the extent of necrosis, as determined by myocardial creatine phosphokinase activity depression and histologic appearance. In the control group ST-segment elevation 15 minutes after CAO (ST15M) predicted changes in Q and R waves 24 hours later; in the treated groups, the same ST15M prior to drug administration resulted in significantly less QRS changes. Thus, 1) Q wave development and R wave fall 24 hours after CAO accurately reflect myocardial necrosis. 2) ST15M predicts subsequent changes in Q and R waves. 3) The efficacy of hyaluronidase and propranolol, agents previously shown to reduce myocardial necrosis, can be detected by less Q wave development and a smaller fall in R wave voltage.
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PMID:Use of changes in the epicardial QRS complex to assess interventions which modify the extent of myocardial necrosis following coronary artery occlusion. 96 48

Fatal myopathy similar to "capture myopathy" described for African game was diagnosed in a wild white-tailed deer. Clinical signs included depression, inability to rise or stand, and myoglobinuria. Values for serum creatine phosphokinase, glutamic oxaloacetic transaminase, and blood urea nitrogen were high. The deer died 42 hours after capture. At necropsy the muscles of the limbs had a waxy, "cooked" appearance and the kidneys were brown. Microscopic findings included severe degeneration and fragmentation of skeletal muscle fibers, nephrosis, centrilobular hepatic necrosis, myocardial degeneration, and anoxic neuronal degeneration.
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PMID:Myopathy and myoglobinuria in a wild white-tailed deer. 97 70

The effects on myocardial function, metabolism and ultrastructure of 60 minutes of reperfusion, instituted after 30, 60 and 90 minutes of occlusion of the left anterior descending coronary artery, were studied in 48 dogs. Twelve sham-operated dogs served as controls. Coronary occlusion for 60 or 90 minutes caused significant depression in the first derivative of left ventricular pressure (dP/dt) (P less than 0.05) that could not be reversed by reperfusion. Upon reperfusion, creatine phosphate stores in myocardium made ischemic for 30 and 60 minutes, but not for 90 minutes, returned toward control levels, but stores of adenosine triphosphate (ATP) and total nucleotides and the ATP/adenosine diphosphate ratio of myocardium subjected to 60 and 90 minutes of ischemia were further decreased. After 60 and 90 minutes of ischemia, swelling of the sarcoplasmic reticulum and mitochondrial damage (swelling, decreased matrix density and partial loss of cristae) were seen. Myofibrils were relaxed in all these groups. Reperfusion produced gross contraction of myofibrils and aggravated these changes in mitochondria and sarcoplasmic reticulum. In the hearts subjected to 90 minutes of ischemia these changes were gross. The levels of creatine phosphokinase, glutamic oxaloacetic transaminase and lactic dehydrogenase in the coronary sinus blood increased dramatically (P less than 0.05) upon reperfusion after 60 or 90 minutes of occlusion, indicating severe impairment of cell membranes. This secondary rise in serum enzyme activity during reperfusion should be taken into consideration when estimating the size of a myocardial infarct from enzyme changes alone. It appears that 60 and 90 minutes of ischemia cause severe myocardial damage that is not reversed by reperfusion maintained for 1 hour although longer periods of reperfusion may be beneficial.
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PMID:Alterations in energy metabolism and ultrastructure upon reperfusion of the ischemic myocardium after coronary occlusion. 108 Mar 52

Eight 5-to 8-week-old Beagle pups were allotted to 4 groups of 2 dogs each. For 55 to 70 days, they were fed either a semisynthetic basal diet (BD) deficient in vitamin E and selenium (Se) (group 1) or the BD supplemented with either 30 IU alpha-tocopherol/kg (group 2), 0.5 ppm Se as selenite (group 3), or 1.0 ppm Se as selenite (group 4). In the dogs fed the BD, clinical signs of vitamin E-Se deficiency developed after 40 to 60 days. These signs were accompanied by increased plasma activity of creatine phosphokinase (CPK) and glutamic oxalacetic transaminase (GOT). The dogs were euthanatized after 10 to 15 days of progressive clinical signs, including muscular weakness, subcutaneous edema, anorexia, depression, dyspnea, and eventual coma. Gross lesions seen at necropsy included ventral subcutaneous edema, generalized skeletal muscular pallor and edema with scattered white longitudinal streaking, prominent brownish yellow discoloration of the intestinal musculature, and a layer of white chalky material at the renal corticomedullary junction. Microscopically, there was evidence of extensive skeletal muscular degeneration and regeneration, focal subendocardial necrosis in the ventricular myocardium, intestinal lipofuscinosis, and renal mineralization. Mean hepatic Se content in the dogs fed the BD was 0.10 ppm (wet weight basis) at necropsy. In the dogs fed the 3 supplemented diets, clinical signs of deficiency did not develop. At necropsy, mild skeletal myopathy was evident histologically in the dogs fed BD and 0.5 ppm Se (group 3) but not in the dogs fed the other supplemented diets. Intestinal lipofuscinosis was found in the dogs fed the 3 supplemented diets but was less severe in the dogs fed the diet supplemented with vitamin E than in those fed diets supplemented with Se.
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PMID:Experimentally induced vitamin E-selenium deficiency in the growing dog. 112 Jul 35

The practise of repeated doping of the sport horse led us to examine its effects on the health of the animal, and particularly on muscular activity. The main doping agent used at present (acepromazine) has already been studied (COURTOT et al., 1974). In this paper, we study the secondary effects of diazepam, a derivative of the benzodiazepine series, which is being used more and more frequently on horses. In treated animals as compared to controls, we observe: -- a slight respiratory depression related solely to effort, -- an increase in seric creatine phosphokinase rate with no apparent relation to effort. A discussion of these results leads to the conclusion that the secondary effects of diazepam are: -- a punctual effect on respiration as related to decreasing effort intensity, -- a toxic effect on muscle.
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PMID:[Effect of tranquilizer doping on the muscular activity of the sport horse. II. -- Diazepam (author's transl)]. 116 58

Previous studies have demonstrated that catecholamines produce massiive disseminated cardiac necrosis closely resembling experimental myocardial infarction. Since catecholamine-induced lipolysis increases myocardial oxygen demand and increased levels of FFA are associated with a depression of myocardial function during myocardial hypoxia, the effect of inhibition of lipolysis on myocardial necrosis induced by isoproterenol was studied. Measurements of creatine phosphokinase (CPK) activity in extracts of whole heart homogenates provide a sensitive and relatively specific index of cellular necrosis. Accordingly, CPK activity was measured in rat hearts 48 hours after the animals had received either isoproterenol, given s.c., 3 times at hourly intervals, or isoproterenol after prior administration of nicotinic acid. Control animals were given saline. With increasing doses of isoproterenol, CPK activity in whole heart homogenates was depressed from 21.7 +/- 0.40 in untreated animals (N = 36) to 14.9 +/- 0.46 in animals given the highest dose of isoproterenol (N = 47). In animals in which isoproterenol-induced lipolysis was inhibited by nicotinic acid, CPK was less depressed (16.3 +/- 0.36, N = 47) than with isoproterenol alone (p less 0.02). Nicotinic acid given alone did not interfere with CPK activity. This study suggests that part of the necrosis induced by isoproterenol is due to increased release and oxidation of FFA in the rat heart.
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PMID:Role of free fatty acids in catecholamine-induced cardiac necrosis. 119 80

The status of myocardial function in rabbits subjected to cardiac catheterization and infection with Streptococcus viridans was assessed at 3 and 6 days. Sham-operated control animals as well as uninfected catheterized animals were used for comparison. Although left heart hypertrophy and interstitial edema were evident in both uninfected and infected animals, the infected animals exhibited in addition mononuclear cell infiltration and muscle degeneration as well as lung congestion and accumulation of pleural fluid. Both uninfected and infected animals has elevated levels of serum creatine phosphokinase, lactic dehydrogenase and glutamic oxaloacetic transaminase as well as electrocardiographic abnormalities such as increased amplitude of the ORS complex and flattening or inversion of the T wave. Unlike findings in the uninfected animals, the serum calcium, magnesium and sodium levels were slightly but significantly decreased and serum potassium levels were increased in the infected rabbits. Both heart rate and pulse pressure were higher in 6 day uninfected and 3 day infected animals whereas 6 day infected animals showed a decrease in heart rate. In comparison to the sham-operated control rabbits and the uninfected animals, the infected animals exhibited depression in the rates of left ventricular pressure development and relaxation as well as prolongation in time for half relaxation in situ. Relative maximal contractile element velocity extrapolated from intraventricular pressure-velocity curves was decreased by 24, 52 and 76 percent, respectively, of control values in the uninfected hearts and those with 3 and 6 days of infection. The isolated perfused hearts from infected animals also generated less contractile force and showed a decrease in the rates of contraction and relaxation, but half-relaxation time was increased. These results demonstrate myocardial dysfunction during experimental bacterial endocarditis and provide evidence that infective cardiomyopathy is associated with heart failure.
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PMID:Alterations in myocardial function during bacterial infective cardiomyopathy. 125 70

This study was undertaken to examine the effects of oxygen free radicals on mitochondrial creatine kinase activity in rat heart. Xanthine plus xanthine oxidase (superoxide anion radical generating system) reduced mitochondrial creatine kinase activity both in a dose- and a time-dependent manner. Superoxide dismutase showed a protective effect on depression in creatine kinase activity due to xanthine plus xanthine oxidase. Hydrogen peroxide inhibited creatine kinase activity in a dose-dependent manner, this inhibition was protected by the addition of catalase. In order to understand the detailed mechanisms by which oxygen free radicals inhibit mitochondrial creatine kinase activity, the effects of oxygen free radicals on mitochondrial sulfhydryl groups were examined. Mitochondrial sulfhydryl groups contents were decreased by xanthine plus xanthine oxidase or hydrogen peroxide; this depression in sulfhydryl groups contents was prevented by the addition of superoxide dismutase or catalase. N-Ethylmaleimide (sulfhydryl group reagent) expressed inhibitory effects on the creatine kinase activity both in a dose- and a time-dependent manner; dithiothreitol or cysteine (sulfhydryl group reductant) showed protective effects on the creatine kinase activity depression induced by N-ethylmaleimide. Dithiothreitol or cysteine also blocked the depression of mitochondrial creatine kinase activity caused by xanthine plus xanthine oxidase or hydrogen peroxide. These results lead us to conclude that oxygen free radicals may inhibit mitochondrial creatine kinase activity by modifying sulfhydryl groups in the enzyme protein.
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PMID:Decrease in heart mitochondrial creatine kinase activity due to oxygen free radicals. 132 80


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