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)

Rapid depression of Ca(2+)-uptake by sarcoplasmic reticulum (SR) vesicles and inhibition of the activity of creatine kinase (CK) and pyruvate kinase (PK) was observed during incubation of enzymes with micromolar concentrations of iron in the presence of adenine nucleotides. This effect of iron was dependent on the redox state of the iron as determined by the redox state of the environment. Redox conditions that generated an Fe2+/Fe3+ ratio close to 1 were most effective in depressing Ca(2+)-uptake by SR vesicles. Redox conditions that decreased the Fe2+/Fe3+ ratio by oxidizing iron were most effective in depressing CK activity while redox conditions that significantly increased the Fe2+/Fe3+ ratio by reducing iron were most effective in depressing PK activity. All iron sensitive enzymes possessed N-etylmaleimide (NEM) sensitive sulphydryl groups that are essential for their activity. The sensitivity to inhibition by NEM increased in the order: PK < Ca(2+)-uptake < CK. Iron initiated depression of CK and PK activities were reversible with dithiothreitol (DTT). This indicated that modification of SH groups was an important step in the mechanism by which iron depressed enzyme activity. Iron initiated depression of Ca(2+)-uptake and of the activity of CK and PK was prevented by not allowing the critical Fe2+/Fe3+ ratio to be reached and by binding of iron with desferroxamine and EDTA. These results, together with data from the literature, led us to suggest that changes in the redox state of cellular micro-environments, inevitably taking place during ischemia and reperfusion, may increase the availability of "low molecular weight iron" and, through changes in the redox state of this iron, selectively initiate reversible depression of several enzymes which contain SH groups essential for their activity.
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PMID:Iron effects on myocardial enzymes depend on redox state. 800 76

In 20 patients receiving cold crystalloid cardioplegia (n = 10) or cold blood cardioplegia (n = 10) during elective coronary artery bypass grafting, the atrial myocardium was tested for glutathione-related antioxidant defenses and lipid peroxidation. In both groups, ischemia and reperfusion induced a significant increase in lipid peroxidation values (p < 0.05) that was associated with a depression of nonprotein thiol compound levels (p < 0.05). Compared with the cold crystalloid cardioplegia-treated patients, the cold blood cardioplegia-treated patients showed a lower lipid peroxidation (p < 0.05) and higher values of nonprotein thiol compounds (p < 0.05). Moreover, a significant ischemia and reperfusion-dependent activation of glutathione transferase was observed only in the cold crystalloid cardioplegia-treated patients. Selenium-dependent glutathione peroxidase and glutathione reductase activities did not change after release of the aortic cross-clamp and did not differ between the two groups. The highest postoperative plasma level of the myocardial-specific isoenzyme of creatine kinase was significantly more elevated in the cold crystalloid cardioplegia patients. Overall, these tissue biochemical features indicate a lower oxidant burden in the myocardium of cold blood cardioplegia-treated patients, a finding suggesting superior protection for the ischemic and reperfused human myocardium also through antioxidant-type mechanisms, apparently medicated by the antioxidant capacity of erythrocytes and specific plasma molecules.
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PMID:Blood cardioplegia reduces oxidant burden in the ischemic and reperfused human myocardium. 801 Jul 96

Tc-99m pyrophosphate (PYP) and Tl-201 simultaneous dual energy single photon emission computed tomography (SPECT) were performed for 33 patients with clinically diagnosed unstable angina. Twenty-two patients (76%) showed PYP accumulation in the myocardium (PYP+group). Clinical features, types of unstable angina, electrocardiographic changes during and after the anginal attack, and serial creatine kinase (CK) sampling data were reviewed and compared in the 2 groups. Selective coronary angiography was performed in all patients, and contrast left ventriculography was carried out in 29 patients both in unstable and stable states. In the study of left ventriculograms, the ejection fraction (EF) was calculated by the area-length method and the wall motion abnormality index was calculated by the centerline method. The PYP(+)group differed significantly from the PYP(-)group in several features as follows: 1) the "new angina at rest" type of unstable angina was more frequent in the PYP(+)group than in the PYP(-)group. The ratios of new angina at rest/effort angina (including new angina of effort and angina of effort with changing pattern) were 16/6; 2/9 for the PYP(+) and (-)groups, respectively (p < 0.05). 2) ST elevation during the heart attack was seen more in the PYP(+)group. The ratios of ST elevation/ST depression were 13/22 (59%); 5/22 (23%) for the PYP(+)group, and 2/11 (18%); 7/11 (64%) for the PYP(-)group, respectively (p < 0.05). 3) EF was improved in the PYP(+) group to the normal range. EF in the PYP(+)group changed from 57 +/- 12 in the unstable state to 62 +/- 11% in the stable state (p < 0.02), while that of the PYP(-)group showed no significant difference between the unstable state (59 +/- 9%) and the stable state (59 +/- 11%). 4) Wall motion abnormality index (WMI) in the PYP(+)group was poorer than in the PYP(-)group, but it improved markedly in one month to the same level as that of the PYP(-)group. WMI in the PYP(+)group in the unstable state (21.7 +/- 26.2) was worse than that in the PYP(-)group in unstable state (5.7 +/- 8.2) (p < 0.001). WMI in the PYP(+)group in the unstable state markedly improved in the stable state (from 21.7 +/- 26.2 to 8.4 +/- 19.8) (p < 0.025); whereas, WMI of the PYP(-)group showed no significant improvement (from 5.7 +/- 8.2 to 15.5 +/- 19.6). These data suggest that the area showing PYP(+) may represent stunned myocardium.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Significance of Tc-99m pyrophosphate accumulation in unstable angina: clinical characteristics and evidence for myocardial stunning]. 816 31

1. The effects of simvastatin and pravastatin on measures of central nervous system activity were investigated in a double-blind, placebo-controlled, randomised crossover study. 2. Twenty-five healthy volunteers sequentially took 40 mg day-1 simvastatin, 40 mg day-1 pravastatin or placebo for 4 weeks, separated by a 4-6 week washout phase. 3. CNS measures included EEG evoked potentials, power spectral analysis, Leeds Sleep Questionnaire, Hospital Anxiety Depression (HAD) Scale, and Digit Symbol Substitution Test (DSST); biochemical measures included plasma cholesterol, liver enzymes (gamma-GT, AST, ALT) and creatine kinase. 4. Mean cholesterol concentrations with both drugs were significantly lower than with placebo, and the cholesterol-lowering effect was greater with simvastatin. There were no significant differences between treatment in EEG evoked potentials, HAD Scale, or DSST scores. On the sleep measure, subjects reported significantly greater difficulty in getting to sleep while on simvastatin than on pravastatin, but neither score differed from placebo. No significant correlations were observed between sleep ratings and either plasma cholesterol concentrations or EEG evoked potentials. 5. The study showed that, while both drugs reduced plasma cholesterol concentrations, neither exerted significant effects, compared with placebo, on EEG evoked potentials, mood, sleep, or cognitive performance after 4 weeks of chronic administration in healthy volunteers.
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PMID:Do cholesterol-lowering agents affect brain activity? A comparison of simvastatin, pravastatin, and placebo in healthy volunteers. 819 30

The incidence of cardiac troponin T (Tn-T) and creatine kinase (CK) isoenzyme MB mass release was studied in 23 patients with stable angina pectoris undergoing visually successful percutaneous transluminal coronary angioplasty (PTCA). Serial blood samples were drawn for measurement of serum Tn-T, CK-MB mass, total CK activity, CK-MB activity, and lactate dehydrogenase isoenzyme (LD-1). ST segment monitoring was carried out during PTCA and for the following 24 hours. None of the patients showed electrocardiographic (ECG) evidence of myocardial infarction. However, Tn-T was elevated in three patients (0.23 to 1.32 micrograms/L), and in these three and an additional three patients CK-MB mass was also elevated (7.0 to 27.5 micrograms/L). Total CK activity and LD-1 were only elevated in one of these six patients. None had elevated CK-MB activity. ST segment depression on ECG recording was not predictive of Tn-T or CK-MB mass release. Patients with elevated Tn-T or CK-MB mass did not differ with respect to demographic data, stenosis characteristics, or in the PTCA procedure. We conclude that CK-MB mass uncovers clinically and ambulatory electrocardiographically inapparent severe myocardial ischemia/minor myocardial damage (microembolization) in 26% (6 of 23) of patients after visually successful PTCA; 13% (3 of 23) had elevated Tn-T, indicating minor myocardial damage. The application of these markers in the future could be of considerable value for determining the efficacy of coronary angioplasty and atherectomy, as well as for drug therapy in connection with such procedures.
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PMID:Cardiac troponin T and CK-MB mass release after visually successful percutaneous transluminal coronary angioplasty in stable angina pectoris. 827 32

This study was undertaken to investigate the effects of oxygen free radicals on myofibrillar creatine kinase activity. Isolated rat heart myofibrils were incubated with xanthine+xanthine oxidase (a superoxide anion radical-generating system) or hydrogen peroxide and assayed for creatine kinase activity. To clarify the involvement of changes in sulfhydryl groups in causing alterations in myofibrillar creatine kinase activity, 1) effects of N-ethylmaleimide (sulfhydryl groups reagent) on myofibrillar creatine kinase activity, 2) effects of oxygen free radicals on myofibrillar sulfhydryl groups content, and 3) protective effects of dithiothreitol (sulfhydryl groups-reducing agent) on the changes in myofibrillar creatine kinase activity due to oxygen free radicals were also studied. Xanthine+xanthine oxidase inhibited creatine kinase activity both in a time- and a concentration-dependent manner. Superoxide dismutase (SOD) showed a protective effect on the depression in creatine kinase activity caused by xanthine+xanthine oxidase. Hydrogen peroxide inhibited creatine kinase activity in a concentration-dependent manner; this inhibition was prevented by the addition of catalase. N-ethylmaleimide reduced creatine kinase activity in a dose-dependent manner. The content of myofibrillar sulfhydryl groups was decreased by xanthine+xanthine oxidase; this reduction was prevented by SOD. Furthermore, the depression in myofibrillar creatine kinase activity by xanthine+xanthine oxidase was protected by the addition of dithiothreitol. Oxygen free radicals may inhibit myofibrillar creatine kinase activity by modifying sulfhydryl groups in the enzyme protein. The reduction of myofibrillar creatine kinase activity may lead to a disturbance of energy utilization in the heart and may contribute to cardiac dysfunction due to oxygen free radicals.
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PMID:Modification of contractile proteins by oxygen free radicals in rat heart. 828 71

The effects of platelet-activating factor (PAF) on cardiac function and contractility and its mechanism of action are not fully understood. The authors investigated the effects of PAF in the absence or presence of a potent PAF antagonist CV-6209 on the cardiac function and contractility; lipid peroxidation product malondialdehyde (MDA), an indirect measure of oxygen free radicals; serum creatine kinase (CK); blood lactate; and pH in anesthetized dogs. CV-6209 (1 mg/kg, IV) did not produce significant changes in the various parameters studied. PAF (1 microgram/kg, IV) produced decreases in the cardiac function (cardiac index, left ventricular work index) and indices of cardiac contractility [(+) and (-) dp/dt, dp/dt at CPIP, (dp/dt)/IP, dp/dt at CPIP/IP, Vmax] and increases in the systemic and pulmonary vascular resistance. It also produced increases in cardiac MDA, serum CK, blood lactate, and H+ and decreases in blood pH and HCO3-. CV-6209 completely prevented the PAF-induced changes in the hemodynamic and biochemical parameters. These results suggest that PAF-induced cardiac depression may be due to PAF-induced release of oxyradicals from neutrophils and that PAF antagonist may be useful in counteracting the deleterious effects of PAF on the cardiovascular system.
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PMID:Platelet-activating-factor-induced changes in cardiovascular function and oxyradical status of myocardium in presence of the PAF antagonist CV-6209. 828 81

In the submitted study the authors evaluate the relationship of the clinical course in patients with inferior myocardial infarction (AIM) in relation to the electrocardiographic (ECG) finding in standard and dextro-lateral leads. In a group of 96 patients (mean age 65 +/- 10 years, 66 men and 30 women) according to the ECG 38 had an isolated inferior AIM (group 1), 28 had signs of extension of the inferior AIM to the posterior wall of the left ventricle (group 2) and 30 patients in group 3 had an extension of the inferior AIM to the right ventricle, i.e. an infarction of the right ventricle. All three groups differed significantly as regards the extent of the AIM according to creatine kinase values (7.1 +/- 4.4 and 18.2 +/- 7.2 resp. and 24.8 +/- 11.6 resp.), as regards mortality (0 and 14% and 37% resp.). In group 2, contrary to the other groups, the significantly most frequent complication was pulmonary oedema (36%) and ventricular tachycardia (30%) and in group 3 the significantly most frequent complication was cardiogenic shock (30%) and advanced atrioventricular block (50%). The cause of death in these patients with infarctions of the right ventricle was cardiogenic shock (n = 6), cardiac rupture (n = 3) and electromechanical dissociation (n = 2). A total of 29 (30%) patients with inferior AIM were treated by temporary pacing: in group 1 21%, in group 2 14% and in group 3 57%. The prognosis of these patients was favourable in groups 1 and 2 (1 of 12 patients died) while in group 3 with infarctions of the right ventricle 9 of 17 patients died (p < or = 0.001). The authors found moreover that patients with precordial depression of the ST segment and inferior AIM have, as compared with patients without this depression, significantly higher creatine kinase values (12.5 +/- 5.5 vs. 5.2 +/- 1.3 mu kat; p < or = 0.001) and a higher general incidence of complications. Patients with inferior AIM are thus a non-homogeneous group from which we can differentiate, based on standard ECG examination and by recording right-sided thoracic leads, patients with an increased risk and start specific treatment in time.
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PMID:[Clinical picture of various types of inferior myocardial infarcts. Clinico-electrocardiographic study]. 837 61

To characterize more fully sacahuiste (Nolina microcarpa Watson) toxicosis in sheep and to evaluate benefits of supplemental Zn, sheep were dosed intraruminally with sacahuiste blossoms. In Trial 1, eight fine-wool sheep (47 +/- 2 kg BW) were fed alfalfa hay at 1% of BW daily and dosed intraruminally with inflorescences amounting to 1% of BW daily, in three portions per day, for 10 d. Four sheep were dosed intraruminally with aqueous ZnSO4 (30 mg of Zn/kg BW) daily for 3 d before initial sacahuiste dosing and on alternate days thereafter, and four sheep were untreated with Zn. Toxicosis was evident within 24 h after initial sacahuiste dosage, involving inappetence, depression, hypokalemia, hypophosphatemia, hyperbilirubinemia, and elevated serum enzymes (alkaline phosphatase, creatine kinase, lactate dehydrogenase, aspartate aminotransferase, and gamma-glutamyl transpeptidase). One sheep (untreated with Zn) died on d 3. Aqueous ZnSO4 alleviated inappetence and suppressed elevation of serum urea N and creatinine but did not suppress other changes in serum clinical profiles. In Trial 2, sacahuiste inflorescences were ruminally dosed into 12 fine-wool wethers (29 +/- 2 kg BW) in amounts equalling 0, .25, .50, .75% of BW per day, and chopped alfalfa hay was provided at 1.75% of BW per day for 14 d. Sacahuiste inflorescenses dosed at .75% of BW elicited severe toxicosis within 24 h, and dosage at .50 or .25% of BW per day increased (P = .12) serum bilirubin. Ruminal fluid pH, mean particle retention time, and particulate passage rate were not affected (P > .10) by sacahuiste, but ruminal fluid passage rate increased 1.6-fold (P < .10) and ruminal fluid volume decreased by 60% (P < .10) in sheep given inflorescenses amounting to .50% of BW daily. Sacahuiste inflorescenses dosed intraruminally at .75% of BW per day elicited ruminal impaction with severe hepatotoxicosis, and dosages amounting to .50% or .25% of BW per day caused similar trends.
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PMID:Characterization of toxicosis in sheep dosed with blossoms of sacahuiste (Nolina microcarpa). 840 61

A Holter monitor was used to record ST segment changes during cesarean section in 170 consecutive healthy parturients starting 2 h before and ending 3 h after surgery. Lumbar epidural anesthesia (LEA, n = 120) or subarachnoid anesthesia (SA, n = 50) was used. Transthoracic 2-D echocardiograms were obtained in 30 patients from the LEA group. ST depression or elevation occurred 160 times in 44 patients from both groups. Ninety-eight percent of these changes occurred between induction of anesthesia and the end of surgery, with 78% of the episodes registering -1 mV. In the LEA group, the number of episodes tended to increase after delivery, but in the SA group, the frequency remained constant. ST segment depression was recorded in 38% and 14% of patients in the LEA and SA groups, respectively (P < 0.05, x2 analysis). No wall motion abnormality was noted in the echocardiogram during ST segment depression. Neither the 12-lead electrocardiogram nor plasma myocardial specific creatine kinase suggested myocardial damage. The operative events, alone or in combination, including hypertension, tachycardia, hypotension, bradycardia, air embolism (precordial Doppler) were neither specific nor sensitive as predictors of ST segment change (stepwise logistic regression). Tachycardia was associated with ST segment changes in 10% of time epochs (5 min) (P = 0.05, x2 analysis). Thus, ST segment changes during cesarean section are not caused by myocardial ischemia and are not of any clinical consequence.
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PMID:Electrocardiographic changes during cesarean section: a cause for concern? 833 96


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