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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The study of the influence of the age of the animals (13 to 53 weeks) on the rate of ethanol metabolism in vivo and the total activity of liver alcohol dehydrogenase and microsomal ethanol oxidizing system showed a progressive decline with age. These effects were observed concomitantly with a diminution in the content of cytochrome P-450 and microsomal functions related to oxidative and free-radical mediated reactions, namely, NADPH oxidase activity, NADPH-dependent oxygen uptake and NADPH-or t-butyl hydroperoxide-induced chemiluminescence. It is concluded that ageing is accompanied by a diminution in the total oxidative activity of the liver tissue, which would explain the depression in basal and ethanol-induced lipid peroxidation found in the oldest group of rats studied.
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PMID:Age-dependent changes in in vivo ethanol metabolism and in the activity of hepatic enzymes involved in ethanol oxidation and microsomal functions. 334 70

The participation of the microsomal ethanol oxidizing system (MEOS) and catalase in total ethanol metabolism is reviewed. Non-alcohol dehydrogenase (ADH) dependent pathways contribute to in vivo ethanol metabolism, but the respective role of each has long been debated. The principal data supporting a role for catalase is an occasionally reported moderate depression of ethanol metabolism after aminotriazole. In deermice lacking ADH, we observed a slight (though not statistically significant) decrease in basal ethanol metabolism of hepatocytes after aminotriazole. However, this decrease was found to parallel a similar inhibition of MEOS by aminotriazole, and thus may not reflect catalase mediated peroxidation in this animal. 1-butanol, a competitive inhibitor of ethanol oxidation by MEOS and not a substrate for catalase, decreased ethanol metabolism by hepatocytes in a concentration dependent manner. These results, as well as those from other investigators, indicate that MEOS mediates virtually all of non-ADH ethanol metabolism in vivo.
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PMID:Ethanol metabolism in alcohol dehydrogenase deficient deermice is mediated by the microsomal ethanol oxidizing system, not by catalase. 342 85

Incubation of freshly isolated rat hepatocytes with highly purified radiolabeled rat transferrin in weakly buffered medium in the presence of 10 mM ethanol resulted in a marked diminution of iron uptake by these cells, associated with a greater pH depression than in ethanol-free control studies. This effect on iron uptake persisted, even when the cells were preincubated for 90 min with ethanol before the addition of transferrin. Increasing the buffering capacity of the system or the addition of a metabolic inhibitor of alcohol dehydrogenase (4-methylpyrazole) returned iron uptake to control values. Acetaldehyde, acetate, lactate (products of ethanol metabolism), and 3-butanol (an alcohol not metabolized by alcohol dehydrogenase) had no influence on iron uptake. Further investigation of iron uptake over the pH range 6-8.5 revealed a marked dependency of iron uptake on the extracellular pH. Leucine incorporation into cell protein was also found to be pH dependent. It is suggested that, in the light of current understanding of transferrin recycling by other cell types, the disturbances of iron homeostasis observed in alcoholics can be partially accounted for by alterations in their acid-base metabolism.
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PMID:Depression of iron uptake from transferrin by isolated hepatocytes in the presence of ethanol is a pH-dependent consequence of ethanol metabolism. 353 28

We investigated the effect of daily oral administration to young rats of lead (10 mg/kg) and ethanol (10%, v/v, in drinking water), either alone or in combination, for 8 weeks on the uptake of lead in tissues, brain biogenic amines, hepatic alcohol dehydrogenase and cytosolic and mitochondrial aldehyde dehydrogenase and some selected lead-sensitive variables. Lead given in combination with ethanol produced more pronounced inhibition in the activities of hepatic glutamic oxalacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) as compared to lead alone treatment. Simultaneous exposure to lead and ethanol produced a greater depression of dopamine (DA) and 5-hydroxytryptamine (5-HT) levels in the whole brain of rats, compared to rats treated with lead alone. The concentrations of lead in blood, liver and brain were significantly higher in rats exposed simultaneously to lead and ethanol. Though ethanol treatment alone inhibited the activities of hepatic alcohol dehydrogenase and cytosolic and mitochondrial aldehyde dehydrogenase, no effect of lead treatment alone on these variables was observed. The results suggested that animals exposed to ethanol and lead are more vulnerable to the neurologic and hepatotoxic effects and the systemic toxicity of lead.
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PMID:Effect of combined exposure to lead and ethanol on some biochemical indices in the rat. 382 40

In vitro studies have shown that acetaldehyde is a more potent inhibitor of testicular steroidogenesis than ethanol. The present study examined the in vivo role of acetaldehyde in ethanol-induced reduction of testosterone by (1) determining the levels of acetaldehyde to which the testes were exposed subsequent to acute ethanol administration to mice; and (2) examining the effect of ethanol on testosterone in animals subsequent to drug pretreatment which decreased or increased ethanol-derived acetaldehyde. Ethanol-induced (3 g/kg) depression of testosterone was dependent upon gonadotropin stimulation. The increase in hCG-induced testosterone was suppressed (P less than 0.01) in ethanol- as compared to saline-treated animals [39.8 +/- 2.6 (S.E.M.) vs 28.1 +/- 2.3 ng/ml]. Pargyline (100 mg/kg) or cyanamide (8.4 mg/kg) increased (P less than 0.05) plasma and testicular acetaldehyde, while having no effect on the testosterone response to ethanol. Similarly, 4-methylpyrazole (25 mg/kg) reduced blood and testicular acetaldehyde to nondetectable levels, while having no effect on testosterone. Testicular acetaldehyde was lower (P less than 0.001) than plasma levels (14 +/- 2 vs 2.0 +/- 0.2 microM). This functional blood-testis barrier to acetaldehyde could be explained by testicular aldehyde dehydrogenases in the mitochondria (Km for acetaldehyde = 1.5 microM) and in the cytosol (Km = 123 microM) whose maximal activities totaled to more than 25-fold greater than that of testicular alcohol dehydrogenase (ADH). ADH was concentrated in the Leydig cells, while aldehyde dehydrogenase was evenly distributed in the testis. Ethanol prevented further hCG-induced rises in testosterone rather than inhibiting testosterone production to below pre-ethanol values. The above data argue against a significant role of acetaldehyde in the in vivo response of testosterone to ethanol. Ethanol appears to impair gonadotropin-testicular receptor interaction in vivo.
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PMID:Demonstration of a functional blood-testis barrier to acetaldehyde. Evidence for lack of acetaldehyde effect on ethanol-induced depression of testosterone in vivo. 397 44

As aged polyuria is often observed in the IVCS strain of mouse, biochemical and histological studies were undertaken in order to clarify its etiology. Polyuria was observed at 7-8 months of age, and significant increases in water intake and urine volume were noted at 10-11 months of age. IVCS strain mice over one year old showed water intakes and urine volumes about five to six times greater than those in DDI strain mice. The osmolarity of urine excreted from polyuric mice was low compared with DDI strain mice, and elevations of sodium and potassium excretion were observed at an early stage of polyuria. At a more advanced stage of the disease, proteins of low molecular weight were excreted in most animals. Furthermore, depression of kidney response to ADH was recognized soon after onset of polyuria compared with normal IVCS strain mice. Thus, polyuria observed in IVCS strain mice may result from a functional defect of the renal tubules. In addition, significant deposition of amorphous substances, especially in the liver, kidney and spleen, occurred almost in parallel with polyuria. From these findings, it is obvious that mice of the IVCS strain exhibit characteristic polyuria and storage disease as they age.
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PMID:Clinical and pathogenic studies on aged polyuria in the IVCS strain of mouse. 401 46

1. Neurones in the supraoptic nucleus were examined for their responsiveness to microiontophoretically applied monoamines and cholinomimetic agents. One hundred and sixty-one of the 749 neurones recorded were antidromically identified as neurosecretory cells.2. The monoamines, dopamine, noradrenaline and serotonin, reduced the activity of all cells which responded.3. Reduction in activity following noradrenaline administration was antagonized by the beta-adrenergic blocking agent MJ-1999 and potentiated by desmethylimipramine.4. Acetylcholine produced either a decrease or an increase in activity of responsive cells with depression the predominant result. Both the depressant and the excitatory response to acetylcholine were seen in individual neurosecretory cells which were depressed by noradrenaline.5. Application of acetyl-beta-methylcholine and carbaminoylcholine consistently resulted in depression of all responsive cells, while nicotine excited the majority of responsive cells. Both types of response were observed on the same neurosecretory cell.6. The depressant response was antagonized by the muscarinic blocking agent atropine while the excitatory response was antagonized by the nicotinic blocking agent dihydro-beta-erythroidine. Responses to acetylcholine were potentiated by the acetylcholinesterase inhibitor physostigmine.7. The data indicate that noradrenaline-containing terminals on these neurosecretory cells are likely to inhibit their discharge rate, while the presumed cholinergic terminals might function as either excitatory or inhibitory, depending on the receptor activated.8. These results support the hypothesis that ADH release is related to the neuronal activity of the supraoptic neurosecretory cell.
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PMID:Noradrenaline and acetylcholine responses of supraoptic neurosecretory cells. 439 77

A total of 132 urine specimens were obtained from 17 depressed patients and 18 controls under conditions of mild water deprivation. Mean values of milliosmoles of solute and millilitres of urine excreted per hour were obtained for each subject. The depressed patients excreted significantly less solute than the control group per unit volume of urine. There was no significant difference between the solute excretion rates of depressed patients and those who had recently recovered from depression-though the trend was towards normality. The significance of these results is discussed in relation to studies on body fluids and electrolytes and the role of ADH and aldosterone in affective disorders.
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PMID:Urine concentration in depressive illness. 555 92

Fentanyl, a synthetic opiate with a (clinical) potency of 50 to 100 times that of morphine, was introduced into clinical practice in the early 1960s. Usually administered by single intravenous doses, it developed a reputation for having a short duration of action and it was assumed that this was a consequence of rapid removal from the body. However, as clinical experience increased, it was realised that administration of multiple doses or large doses during narcotic-based anaesthesia sometimes led to delayed recovery and prolonged respiratory depression, suggesting that the duration of action was limited by redistribution within the body rather than removal from the body. Recent developments in analytical techniques have allowed pharmacokinetic studies and these have confirmed this opinion; fentanyl is rightly regarded as having a redistribution-limited duration of action after single or infrequent doses (analogous to thiopentone). However, the magnitude of the pharmacokinetic constants reported for fentanyl are remarkably inconsistent even in healthy volunteers, for reasons apparently only explainable by assay differences. Hence, estimates of apparent volume of distribution (area) range from around 60L to over 300L, estimates of terminal half-life range from about 1.5 to 6 hours (15 hours in geriatric patients) and total body clearance ranges from 0.4 to over 1.5 L/min. Renal excretion accounts for up to 10% of the dose; the remainder of the clearance would appear to be predominantly hepatic, but with contributions from other tissues. Continued clinical developments of narcotic-based anaesthetic techniques have resulted in high doses of narcotic being used, with oxygen, as the sole anaesthetic agents. At present these techniques are usually based on fentanyl, and the technique is frequently called 'stress-free anaesthesia' because of the effects in obtunding the 'stress response' caused by surgery (elevation of plasma concentrations of cortisol, glucose, ADH, etc. in the intra- and post-operative period) and the lack of deleterious effects on the cardiovascular system.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Clinical pharmacokinetics of fentanyl and its newer derivatives. 622 71

The DNA segments containing the ADR1 gene and a mutant allele, ADR1-5c, have been isolated by complementation of function in Saccharomyces cerevisiae. The ADR1 gene is required for synthesis of the glucose-repressible alcohol dehydrogenase (ADHII) when S. cerevisiae cells are grown on a nonfermentable carbon source, whereas the ADR1-5c allele allows ADHII synthesis even during glucose repression. A plasmid pool consisting of yeast DNA fragments isolated from a strain carrying the ADR1-5c allele was used to transform a strain containing the adr1-1 allele, which prevents ADHII depression. Transformants were isolated which expressed ADHII during glucose repression. A plasmid isolated from one of these transformants was shown to carry the ADR1-5c allele by its ability to integrate at the chromosomal adr1-1 locus. The wild-type ADR1 gene was isolated by colony hybridization, using the cloned ADR1-5c gene as a probe. The ADR1-5c and ADR1 DNA segments were indistinguishable by restriction site mapping. A partial ADR1 phenotype could be conferred by a 1.9-kilobase region, but DNA outside of this region appeared to be necessary for normal activation of ADHII by the ADR1 gene.
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PMID:Isolation and characterization of the positive regulatory gene ADR1 from Saccharomyces cerevisiae. 634 14


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