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)

A coincubation system composed of hepatocytes in primary monolayer culture and erythrocytes suspended in the culture medium was developed and used as a model for investigations of mechanisms of cyanide antidote action at the cellular level. Hepatocyte ATP was used as the cytotoxicity indicator. Treatment of rat hepatocytes in the coincubation system with KCN (1.0 mM) for 10 min at 37 degrees C selectively reduced hepatocyte ATP levels to 33 +/- 15% of control (no KCN added) levels. 4-dimethylaminophenol (DMAP), cobalt(II) chloride, sodium nitrite, sodium thiosulfate, or a combination of the last two antidotes added to the KCN-containing medium significantly reversed ATP depression and the response was concentration dependent. The relative effectiveness, on a molar basis, was estimated to be DMAP greater than CoCl2 much greater than NaNO2 congruent to Na2S2O3. NaNO2 and DMAP induced methemoglobin formation in the absence of cyanide and cyanmethemoglobin formation in its presence; erythrocytes were required in the medium for effectiveness. CoCl2 produced neither cyanmethemoglobin nor thiocyanate in appreciable quantities nor required erythrocytes for antagonism. Na2S2O3 converted cyanide to thiocyanate and reversed ATP depression without erythrocytes in the medium. The addition of erythrocytes increased these rates significantly and to a greater extent than albumin. The overall results are consistent with previously proposed modes of action for these antidotes. However, the enhancement in cyanide metabolism and ATP recovery with Na2S2O3 and erythrocytes in the system was unexpected and raises the possibility that erythrocytes may contribute to cyanide disposition and antagonism in vivo when this antidote is administered.
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PMID:Application of a hepatocyte-erythrocyte coincubation system to studies of cyanide antidotal mechanisms. 356 31

The in vivo hepatic lipid peroxide content of rats was increased by aspirin or 4-pentenoic acid (4-PA) administration but was decreased by clofibrate (CPIB) administration. The increase by aspirin or 4-PA treatment was depressed by simultaneous administration of CPIB. However, the in vitro formation of lipid peroxide in liver mitochondria and microsomes of rats treated with CPIB as well as aspirin and 4-PA was also elevated compared to that of control rats. The formation of lipid peroxide in mitochondria and microsomes of control rats in vitro was depressed by the addition of cytosols obtained from untreated (control), aspirin-treated, 4-PA-treated, and CPIB-treated rats, but was not depressed by the addition of albumin or heated cytosols. The most effective depression was obtained by the addition of cytosol obtained from CPIB-treated rats. In addition, glutathione peroxidase activity and nonprotein sulfhydryl content in cytosol obtained from CPIB-treated rats were elevated compared to those from control, aspirin, and 4-PA-treated rats. The results suggest that the action of CPIB may be mainly related to the increase of cytosolic glutathione peroxidase activity and nonprotein sulfhydryl content. Hepatic triglyceride and phospholipid contents of rats treated with aspirin or 4-PA were increased compared to those of control rats. These increases were also reversed by simultaneous administration of CPIB.
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PMID:Effect of clofibrate on lipid peroxidation in rats treated with aspirin and 4-pentenoic acid. 357 Dec 11

To assess whether myocardial lipid metabolism is altered in the "stunned" myocardium we have studied the metabolism of (1-14C)-palmitate during reperfusion in a modified rat heart preparation. Hearts were perfused retrogradely at a physiological flow rate (2 ml/min) in a non-recirculating system with erythrocyte-enhanced Krebs-Henseleit buffer containing albumin 0.4 mM, glucose 11 mM, palmitate 0.4 mM and trace amounts of (1-14C)-palmitate. Left ventricular pressure was measured by a latex balloon in the left ventricular cavity. Control hearts were perfused at constant flow for 120 min. To achieve reversible ischaemic damage, myocardial perfusion was reduced by 95% for 40 min, followed by reperfusion at the control flow rate for 60 min (reperfusion group). For comparison, irreversible damage was produced by calcium free perfusion (calcium paradox group). In the reperfusion group, the developed pressure was severely depressed 5 min after reperfusion to 23% of the value in the control group (p less than 0.05) but recovered to 84% (NS) at 60 min. In the calcium paradox group, mechanical activity ceased completely without recovery. Myocardial uptake of (1-14C)-palmitate in the reperfusion group was similar to the control experiments for the entire reperfusion period, whereas a marked depression was observed in the calcium paradox group. 14CO2 production was severely depressed at the onset of reperfusion in both the reperfusion and calcium paradox group to 42% (p less than 0.05) and 29% (p less than 0.05) respectively. In contrast to the calcium paradox group, 14CO2 production in the reperfusion group recovered progressively to 70% (NS) of the control value during the 60 min of reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Free fatty acid metabolism in "stunned" myocardium. 366 5

The hypothesis that the toxic effects of imidocarb mediated by reduced cholinesterase activity might be intensified by hypomagnesaemia was tested in calves. Hypomagnesaemia was induced in 12 males (50 kg) using an artificial milk based on a commercial nondairy coffee creamer. Although plasma magnesium levels reached 0.33 mmol litre-1 in two weeks no clinical signs were detected. In 12 control calves a daily magnesium supplement of 0.6 g was inadequate although the published requirement is 0.45 g; it was raised to 1.2 g to keep plasma magnesium normal. Lighter calves developed hypomagnesaemia more readily and fast-growing calves had lower plasma urea concentrations. Plasma calcium, but not plasma magnesium, showed significant positive correlation with plasma albumin. The only statistically significant effects of hypomagnesaemia were slight elevations of white cell count and plasma sodium. The hypomagnesaemic and normomagnesaemic calves were divided into two equal groups and treated with 3.3 mg kg-1 of imidocarb dipropionate or a placebo. The drug produced the expected clinical signs of mild toxicity and depression of cholinesterase but no other adverse effects. Transient slight depressions of plasma calcium and potassium concentration, a transient rise of plasma sodium and elevation of creatine kinase occurred. None of the effects of imidocarb treatment was intensified by hypomagnesaemia except, perhaps, constriction of the pupils; generally, hypomagnesaemic animals were affected less.
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PMID:Effect of induced hypomagnesaemia on the toxicity of imidocarb in calves. 370 46

Delayed hypersensitivity was assessed with four antigens, viz. purified protein derivative of tuberculin (PPD), Candida albicans, streptokinase/streptodornase and mumps, 48 hours before and 24 hours after elective major abdominal surgery in 24 patients. Cumulated areas of skin response were recorded on the basis of readings 24 and 48 hours after antigen stimulation. A control group of 16 patients was similarly assessed, but without surgery between the two test occasions. Retesting in this control group increased the cumulated skin response area in all patients. The respective means for the two tests were 1 290 +/- 222 to 2 330 +/- 365 mm2 (p less than 0.0001), demonstrating a pronounced booster action by the initial test. In contrast, the surgical patients showed a decrease, from 1 559 +/- 203 preoperatively to 1 230 +/- 210 mm2 postoperatively (p = 0.14). The postoperative response was significantly lower than the retesting response in the controls without surgery (p = 0.02), indicating that surgery leads to depression of delayed hypersensitivity response. The preoperative cumulated skin test response correlated with age (r = -0.66, p less than 0.001) and with serum albumin (r = 0.59, p less than 0.01). Postoperative depression of the skin test response also was related to age (r = 0.53, p less than 0.01) and with postoperative fall in s-albumin (r = 0.51, p less than 0.05). The results emphasize that interpretation of serial skin testing in surgical patients is not adequate unless comparison is made with a similar retesting regimen in nonsurgical patients.
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PMID:Influence of surgery, age and serum albumin on delayed hypersensitivity. 371 36

Zinc and vitamin A concentrations in the serum were measured in 40 alcoholics (33 males and 7 females) and 35 healthy, age-matched subjects (31 males, 4 females). Liver zinc concentrations were measured in 15 alcoholics from specimens collected by liver biopsy and compared with the zinc concentrations in liver specimens taken at autopsy from victims of road-traffic accidents. Alcoholics had significantly lower serum concentrations of both zinc and vitamin A compared to the control group of healthy subjects. The depression of zinc and vitamin A levels was related to the severity of the hepatic lesions, the lowest levels being observed among cirrhotics. Liver zinc concentrations were similar in alcoholics and healthy subjects and were not related to plasma zinc concentrations. Serum zinc and vitamin A levels were positively correlated among cirrhotics, but not in other alcoholics or controls. Thus low levels of vitamin A in cirrhotics may have arisen as a result of impaired mobilisation from the liver due to zinc deficiency, or to non-availability of hepatic zinc. Female alcoholics were more severely affected than males with respect to their zinc and vitamin A levels, although they consumed lesser amounts of alcohol and had a shorter duration of alcohol intake. A strong positive relationship existed between zinc and albumin levels in all alcoholics but not in controls. It is possible that the decreased serum albumin levels may have limited the availability of albumin for the transport of zinc in the plasma and this in turn may have resulted in increased urinary excretion of zinc.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Zinc and vitamin A status of alcoholics in a medical unit in Sri Lanka. 376

Drug-induced nephrotoxicity (NT) has become an increasingly significant clinical problem. An in vitro model of drug-induced NT was therefore developed using gentamicin and the effects of ATP-MgCl2 on reduction or prevention of NT were determined. To study this, non-pulsatile perfusion in isolated rat kidneys was maintained at 100 mm Hg during 2 hr of perfusion at 37 degrees C. The oxygenated Krebs-HCO3 perfusate contained 7.5 g/dl albumin as colloid, glucose, creatinine, amino acids, trace amounts of [3H]inulin and 125I-lysozyme, and either 0, 0.4, 0.8, or 1.2 mg/ml of gentamicin. In some studies, 2 mM ATP-MgCl2 was added with 0.8 mg/ml of gentamicin at 0 and 60 min of perfusion. During each 10-min clearance period, glomerular filtration rates, sodium absorption, water absorption, and fractional clearance of TCA-precipitable lysozyme were measured. The results indicate that renal perfusate flow, glomerular filtration rate, urinary flow and tubular absorption of protein (a sensitive indicator of tubular function), sodium, and water were affected by gentamicin in a dose-dependent manner. An isolated kidney preparation can therefore be used to study gentamicin-induced NT. Higher in vitro perfusate concentrations of the drug were needed, however, to acutely mimic the in vivo cumulative effects. Nonetheless, renal perfusate flow, glomerular filtration rate, and the depression in protein reabsorption which occurred with gentamicin treatment were markedly improved by simultaneous treatment with ATP-MgCl2. Thus, ATP-MgCl2 may be useful in reducing drug-induced nephrotoxicity.
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PMID:Reduction of the drug-induced nephrotoxicity by ATP-MgCl2. II. Effects on gentamicin-treated isolated perfused kidneys. 387 64

2-Deoxyglucose uptake (3 min) and 3-O-methylglucose transport (2 s) was measured in rat adipocytes preincubated with 5 microM epinephrine plus adenosine deaminase as described by Green (Green, A. (1983) FEBS Lett. 152, 261-264). 2-Deoxyglucose uptake was about 95% depressed in insulin-treated, but not in 'basal', cells preincubated with epinephrine plus adenosine deaminase for 60 min in broad agreement with Green's report. However, this depression was caused by a decrease in sugar phosphorylation rather than transport. In similarly incubated cells, transport of 3-O-methylglucose, a sugar analogue not phosphorylated in the adipocytes, was not affected by catecholamine plus adenosine deaminase. However, a decrease in transport of about 60% was observed both in the absence and the presence of insulin when the albumin concentration was high enough and the cell concentration low enough to prevent accumulation of free fatty acids in the medium. In addition, the insulin sensitivity with regard to hexose transport was markedly reduced. Transport was approximately doubled in cells incubated with 5 microM epinephrine in the absence of adenosine deaminase. Thus, epinephrine at a high concentration stimulates hexose transport in the absence of adenosine deaminase (presence of adenosine) whereas it inhibits both basal and insulin-stimulated transport in the presence of adenosine deaminase (absence of adenosine).
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PMID:The effect of catecholamines and adenosine deaminase on the glucose transport system in rat adipocytes. 389 Sep 59

Tumor bearing patients have repeatedly been shown to develop states of protein (PD). PD has frequently been associated with depression of acquired immunity. In contrast, little is known about the effects of PD on natural killer (NK) cell cytotoxicity and on bone marrow cellularity and how modulation of these parameters by maleic anhydride divinyl ether copolymer (MVE-2) would be affected. BALB/c mice 6-10 weeks old were fed normal diets (18% protein) (ND mice) or protein deficient isocaloric diets (PD mice) for 35 days. On days 5, 9, 15, 23, and 35 assays were performed. Three days prior to each assay day, some groups received MVE-2 i.p. In PD mice spontaneous NK activity was reduced by some 80%. After MVE-2 the levels only rose to half the amount of activity of ND mice, although in both groups an increase of NK activity took place. BMC levels of PD mice were also strongly decreased. After MVE-2, increases of BMC in PD mice were quite weak and did not reach the level of normal unstimulated BMC. In PD mice we found body weight loss of 46%, reduction in albumin and total protein of 22% and complete disappearance of prealbumin after 5 days of diets. Preliminary results indicate that repletion with amino acids (NeoAminomel L12.5 o.K.H. Salvia, Boehringer Mannheim Co.) is able restore NK activities and BMC levels.
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PMID:Effects of protein depletion on NK cell cytotoxicity and bone marrow cellularity. 393 73

After surgical placement of end-to-side portacaval shunts (PCS), 4 adult mongrel dogs (11.8 to 18.2 kg) were fed purified diets and monitored for approximately 50 weeks for changes in body weight, neurologic status, and an array of clinically important biochemical variables. Two healthy dogs, fed the same diets and maintained in the same environment, were also observed (controls). Body weights were relatively stable over the period of observation. The branched-chain ratio ([valine] + [leucine] + [isoleucine]/[phenylalanine] + [tyrosine]), an index of the degree of change in plasma amino acid concentrations, was significantly lower in dogs with PCS than in controls. Despite this depression in branched-chain ratio, the principals (dogs with PCS) were essentially free of neurologic symptoms. Statistically significant decreases due to portacaval shunting were seen in the serum concentrations of glucose, calcium, urea nitrogen, creatinine, cholesterol, and albumin. Total protein, globulin, and triglyceride concentrations tended to be lower in the serum of principals than in serum of controls, but the differences were not statistically significant. Statistically significant increases due to portacaval shunting were seen in plasma concentrations of total conjugated bile acids and sulfobromophthalein retention. Concentrations of the following compounds tended to be higher in serum of principals than in serum of controls: phosphorus, chloride, uric acid, total bilirubin, lactate dehydrogenase, aspartate transaminase, alanine transaminase, and alkaline phosphatase. Liver biopsy at 7 months after operation showed mild-to-extensive atrophy of hepatocytes, mild-to-extensive fibrosis, and collapsed portal veins in all principals examined.
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PMID:Long-term biochemical and physiologic effects of surgically placed portacaval shunts in dogs. 395 18


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