Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The impact of low level lead exposure on human central nervous system function is a major public health concern. This study addresses the inhibition of the cation pump enzyme Na, K-ATPase by low level lead. Human brain tissue was obtained at autopsy and frozen until use. Brain homogenates were preincubated with PbCl2 for 20 min at 0 degrees C. Inhibition of K-paranitrophenylphosphatase (pNPPase), a measure of the dephosphorylation step of Na,K-ATPase, reached steady state within 10 min. K-pNPPase activity, expressed (mean +/- SEM) as a percentage of control (45.2 +/- 2.7 nmol/mg/min), fell to 96.3 +/- 0.9% at 0.25 uM [PbCl2] to 82.0 +/- 1.6% at 2.5 uM [PbCl2] in homogenates prepared from normal brain. Similar results were obtained with homogenates prepared from brains of patients with a history of alcohol abuse and of those with other miscellaneous conditions. Since the mean blood level of lead in the United States has ranged recently from 9.2 to 16.0 ug/dl (0.44 to 0.77 uM), these results indicate that current in vivo levels of lead exposure may impair important human brain function.
 ...
PMID:Low level lead inhibits the human brain cation pump. 185 20

Previously we reported that abstaining chronic alcoholic men demonstrated significantly more nighttime hypoxemia than a control group. Here, we report a replication employing a larger sample of abstaining chronic alcoholics and a more appropriate control group than that used in the previous study. Forty-seven males, 48.4 +/- 1.7 years of age (mean +/- SEM), reporting 24.8 +/- 1.5 years of heavy alcohol use, comprised the abstaining alcohol group. Thirty-five age- and weight-matched males, 50.3 +/- 1.7 years were the control group. The alcohol group had significantly more nighttime oxygen desaturations below 90% than did the control group (16.9 +/- 3.3 vs. 6.2 +/- 1.4, F = 7.8, p less than 0.01), with significantly higher percentages of individuals in the alcohol group manifesting more than 10 or 20 oxygen desaturations below 90%. Regression analyses within the alcohol group revealed that severity of alcohol abuse, but not age, body mass index, days abstinent, or smoking significantly predicted levels of nighttime hypoxemia. These results confirm our original observation of increased nighttime hypoxemia in abstaining chronic alcoholic men and suggest that long-term alcohol abuse may be a risk factor for development of sleep apnea.
 ...
PMID:Nighttime hypoxemia is increased in abstaining chronic alcoholic men. 217 70

Fatty acid ethyl esters, a family of ethanol metabolites, are formed by esterification of ethanol with fatty acids and have been detected in human organs commonly damaged by ethanol abuse. Because alcohol-related deaths may occur up to six times as often as reported on death certificates, we undertook quantitation of these potentially longer-lived alcohol metabolites in postmortem human adipose tissue to assess their usefulness as a measure of recent ethanol exposure. After isolation and identification using sequential thin-layer and gas chromatography, fatty acid ethyl esters were present in adipose tissue of chronic alcoholics (mean +/- SEM equals 300 +/- 46 nmol/g), even though blood ethanol concentration at the time of death was undetectable. Unintoxicated nonalcoholic subjects who had no history of alcohol abuse had concentrations seven times lower (mean +/- SEM equals 43 +/- 13 nmol/g). In vitro studies demonstrate that fatty acid ethyl esters are synthesized by human adipose tissue in proportion to the ethanol concentration present and their half-life in adipose tissue of laboratory animals is 16 +/- 1.6 hours, ie, fourfold greater than that of alcohol. These results indicate that fatty acid ethyl esters are long-lived ethanol metabolites whose persistence and accumulation in adipose tissue may allow an accurate diagnosis of significant alcohol consumption even when ethanol has been completely eliminated from the body.
 ...
PMID:Fatty acid ethyl esters in adipose tissue. A laboratory marker for alcohol-related death. 274 58

To investigate whether anterior pituitary function is disturbed in chronic alcoholic men after a period of alcoholic abuse, TSH and PRL secretagogues were given to such patients in the acute and late withdrawal states (1 and 8 days after admission to hospital, respectively). The TSH and PRL responses were compared with those obtained in a group of control patients without a history of alcohol abuse. Twenty five micrograms of TRH, injected iv in six alcoholic men during acute withdrawal, raised TSH by 1.6 +/- 0.8 (SEM) microU/ml and PRL by 18 +/- 7 ng/ml. In the seven control patients the corresponding responses were significantly larger (7.8 +/- 1.4 microU/ml, P less than 0.01; and 56 +/- 10 ng/ml, P less than 0.02, respectively). When the alcoholics were reinvestigated in the late withdrawal state their TSH and PRL responses increased significantly to 2.9 +/- 1.1 microU/ml (P less than 0.05) and 41 +/- 9 ng/ml (P less than 0.05), respectively. To determine whether dopaminergic inhibition contributed to the reduced TSH and PRL responsiveness in the acute withdrawal state, six additional chronic alcoholic men were tested with oral metoclopramide. This drug, which has dopamine D2-receptor blocking properties, induced similar PRL responses (7- to 8-fold PRL increments) in the acute and late withdrawal states but did not alter TSH. Furthermore, TRH, injected 90 min after oral priming with metoclopramide in six additional alcoholics, elicited TSH and PRL increments in the acute withdrawal state which did not differ significantly from those obtained in the late withdrawal state (TSH, 3.5 +/- 0.9 vs. 4.1 +/- 1.2 microU/ml; PRL, 27 +/- 3 vs. 24 +/- 6 ng/ml). These findings suggest that dopaminergic inhibition of the thyrotrophs and lactotrophs may be responsible for the blunted TSH and PRL responses to TRH during the acute withdrawal period in chronic alcoholic patients.
 ...
PMID:Prolactin and thyrotropin responses to thyrotropin-releasing hormone and metoclopramide in men with chronic alcoholism. 643 73

A group of 73 patients suffering from painful alcoholic, chronic pancreatitis, hospitalized from 1971 to 1981, has been analyzed retrospectively. The aim was to assess the effects of alcohol withdrawal and pancreatic surgery on the course of pancreatic pain. The mean number of years during which the patients complained of pain was 3.5 +/- 0.5 (m +/- SEM). At the end of follow-up, 70 p. 100 of the patients did no longer suffer, alcohol withdrawal was obtained in 45 p. 100 and surgery had been performed in 41 p. 100. Continued alcohol abuse did not prevent pain relief: 60 p. 100 of patients continuing to drink at the end of follow-up, did not suffer any longer. One year after pancreatic surgery, pain relief was more frequent, if alcohol abstinence had been obtained before surgery (p less than 0.01). Among the 53 patients followed up to 5 years after the start of pain: a) the cumulative actuarial probability of disappearance of pain was 17 p. 100 at 2 years, 52 p. 100 at 5 years, 62 p. 100 at 8 years after the start of pain. Alcohol abstinence and surgery were observed during the first five years of pain; b) the mean number of years of pain was lower among the patients who became abstinent early (less than 4 years after the beginning of pain) than among those who did not (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Chronic alcoholic pancreatitis: relation of pain to withdrawal and pancreatic surgery]. 673 54

Alcohol abuse is commonly associated with reduced bone mass and osteoporosis as a consequence of both systemic and direct cellular effects. To clarify some of the pathways by which alcohol exerts its actions directly on bone cells, we investigated the formation of early osteoblast progenitors (colony-forming units for fibroblasts; CFU-F) in long-term murine and human bone marrow cultures exposed to ethanol and to its main metabolite, acetaldehyde. In murine bone marrow cultures, obtained from Swiss female mice, ethanol inhibited CFU-F formation (maximal reduction +/- SEM: 50 +/- 2%; p < 0.01) at concentrations ranging from 0.04% to 0.6% that are similar to those reached in vivo in alcoholics. Acetaldehyde strongly reduced CFU-F formation at concentrations of 0.004% and 0.02%, and completely abolished it at the dose of 0.06%. Similarly, ethanol (at concentrations > or =0.02%) and acetaldehyde (from 0.004% to 0.06%) significantly decreased the number of CFU-F in human bone marrow cultures; the mean reduction observed with ethanol was 63 +/- 12% (p < 0.05), whereas acetaldehyde completely prevented CFU-F formation at the concentration of 0.06%. These in vitro observations were confirmed by the in vivo findings that the CFU-F formation in bone marrow cultures from nine young, chronic, noncirrhotic alcoholics was significantly reduced (70 +/- 15%), compared with seven age-matched normal subjects (p < 0.01). In addition, acetaldehyde inhibited cell proliferation in human osteoblastic cells (MG-63 and HOBIT cell lines), whereas ethanol reduced proliferation only in MG-63 cells. Our results indicate that ethanol and acetaldehyde may directly inhibit the osteoblastogenic potential of the bone marrow, and this effect may contribute to the decreased bone formation observed in alcoholics.
 ...
PMID:Ethanol and acetaldehyde inhibit the formation of early osteoblast progenitors in murine and human bone marrow cultures. 1006 72

Substance abuse is a major and prevalent public health concern among university students. Tobacco smoking, risky alcohol behavior, and illegal drug consumption may lead to health problems and behavioral and academic issues. Several individual and environmental factors associate with substance abuse in this population, and the mediating effect of alcohol abuse in the relationship between tobacco smoking and drug consumption is yet to be explored. The purposes of this study were to evaluate the association of individual and environmental factors and substance use, and to analyze the relationship between tobacco smoking, alcohol abuse, and drug consumption, considering alcohol abuse as a possible mediator. A total of 550 Spanish undergraduate and postgraduate students completed several questionnaires regarding their smoking status, alcohol use, and drug consumption during the last six months. Bivariate and multivariate analyses were conducted to explore associations between factors. Direct, indirect and mediating effects were tested using a partial least squares approach (PLS-SEM). The results indicated that substance abuse is associated with being male, living with other students, and combined substance consumption. PLS-SEM showed a significant effect of tobacco smoking and alcohol abuse on drug consumption. Alcohol abuse plays a mediating role in the relationship between tobacco smoking and drug use.
 ...
PMID:Individual and Environmental Factors Associated with Tobacco Smoking, Alcohol Abuse and Illegal Drug Consumption in University Students: A Mediating Analysis. 3234 13