ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1982.tb05375.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Ethanol‐induced behavior is related to the age of the organism. This relationship has been shown for several different kinds of measures, e.g., voluntary consumption of ethanol, effects of acute and chronic administration of ethanol. The usefulness of studies concerned with voluntary ethanol consumption and aging is questioned. Usually, causal mechanisms are not determined and blood ethanol levels are not measured in these animal studies.Both acute and chronic studies have shown that old animals are more sensitive to the effects of ethanol as compared to young animals. This effect has been reported in studies employing a number of different methods of administering ethanol, e.g., injection, inhalation, liquid diet. Age‐related effects in response to short‐term administration of ethanol have been observed for measures such as loss of the righting reflex, general motor activity, hypothermia, and withdrawal signs. Long‐term administration of ethanol has been found to affect brain chemistry, performance, and life span. Explanations for the effects of ethanol among different age groups include differences in the rate of metabolism of ethanol, the percentage of body water and lean body mass, and changes in central nervous system sensitivity.The study of the relationship between the effects of ethanol and aging is relatively new. The most obvious conclusion that can be made from a review of the literature is that much more work needs to be done. Greater attention needs to be given to the theoretical and methodological issues associated with aging r

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1982.tb05376.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Cognitive performance declines moderately with normal aging and severely with pathological aging. A similar range of intellectual impairment has been described in association with prolonged alcohol consumption. It is doubtful that all types and degrees of alcohol‐associated impairments of cognitive function are attributable only to thiamin deficiency. Evidence from human and animal data indicates increasingly that alcohol per se has direct CNS toxic effects as well, and it is dangerous to suggest that adequate thiamin consumption alone would prevent all CNS toxic effects of chronic alcohol consumption.If a direct role of ethanol in CNS toxicity is accepted, it becomes important to study the molecular basis of the behavioral impairment caused by both aging and alcohol abuse in order to develop rational treatment and prevention. An entire spectrum of relationships is possible between aging and alcohol‐related CNS changes. At the one end of the spectrum could simply be deficits additive at the behavioral level but caused by different molecular events. Conversely, molecular processes of biological aging could interact with molecular effects of ethanol, potentiating each other and culminating in an accelerated aging process. Many pathological mechanisms could lead to an irreversible loss of neuronal cell bodies. However, changes in peripheral cell processes, including the synapses, may be equally important in limiting interneuronal communications that result in behavioral deficits. Some changes could even be limited to a decrease of numbers or affinity of synaptic receptor molecules of a particular region. From the human and animal data reviewed, chronic ethanol consumption appears to increase some behavioral deficits caused by aging. What the exact interrelationships are at the molecular basis for the behavioral changes is not yet cl

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1982.tb05377.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1982.tb05378.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Neuroradiological studies have consistently demonstrated that alcoholics have morphological abnormalities of cortical, ventricular, and cerebellar structures suggesting brain atrophy. This atrophy is weakly correlated with impaired psychological test performance. Because brain atrophy and intellectual impairment can also be found in normal aging it is necessary to compare alcoholics with age‐matched control subjects.It is currently unknown if alcohol‐associated brain atrophy and intellectual impairment are the result of conditions preceding alcohol consumption or conditions only indirectly related such as head trauma or other associated diseases. Direct alcohol toxicity would be supported by quantitative alcohol‐atrophy dose‐response relationships and by a partial reversal of atrophy and functional impairment following abstinence from alcohol.Because of methodological difficulties inherent in neuroradiological research, data on the exact pathogenesis of abnormalities in alcoholics have not been produced. The design of such studies can be improved to increase the probability that the causes of brain atrophy will be elu

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1982.tb05379.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

In two samples of employed men (ns of 102 and 496), the amount of alcohol typically consumed per drinking occasion was significantly associated with decreased sober abstraction performance. Age was also significantly related to reduced abstraction scores. An increase of one drink in the quantity of alcohol typically consumed was associated with an average reduction in abstraction performance equivalent to 3.7 more yr of age in one sample and 2.4 more yr of age in the other sample.

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1982.tb05380.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1982.tb05381.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Proliferation‐competent primary ‘monolayer’ cultures of adult rat hepatocytes that display a repertoire of differentiated functions have been characterized for growth state‐dependent expression of alcohol dehydrogenase activity (ADH; EC 1.1.1.1). Following hepa‐tocyte isolation and early during in vitro lag phase, ADH ‘per cell’ is equivalent to control adult liver tissue levels. Upon entry into and progression of logarithmic growth, ADH declines biphasically to about 2% of control levels (halftime rate, R[disappearance]= 3.4 and 7.4 hr; days 0‐is(halftime rate, R[disappearance]= 3.4and 7.4, respectively). increases biphasically as hepatocytes enter and remain in stationary phase (R[disappear]= 3.9 and 11.1 hr; days 6–10 and 10–14, respectively). Ultimately, control ADH is restored. Similar ‘U‐shaped’ curves occur when rates of conversion of [14C]ethanol into CHCI3:CH30H (2:1) extractable material are measured. By this criterion, 10‐ to 13‐day‐old hepatocyte cultures convert ethanol or [14C]acetate 10 times faster than stationary‐phase 3T3 fibroblasts' (3000 or 12,000 cpm/106cells/24 hours versus 200 or 800 cpm/106cells/24 hr, respectively). Both conversion processes in matured hepatocyte cultures depend on extracellular glucose levels unlike the nonhepatocyte system. Furthermore, depending on the growth state, [14C]ethanol conversion in hepatocyte cultures is inhibited up to 73% by 1 mil pyrazole, a specific ADH inhibitor. At higher initial ethanol levels (50 mil), pyrazole blockade is ineffective. The results indicate that, in this long‐term culture system, normal adult hepatocytes retain non‐ADH ethanol‐converting enzymes and pharmacologically‐sensitive ADH. Changes in the latter enzyme's activity levels in culture appear to simulate normal developmental ch

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1982.tb05382.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

Properties of long‐term cultures of hepatocytes isolated from nutritionally maintained adult rats treatedin vivofor 8–12 days with ethanol to achieve blood levels of 200–220 mg ethanol/dl (experimental group) and from isocalorically maintained mock‐treated (control) rats were compared. Two kinds of treatment protocols were used: intragastric intubation or inhalation chambers. Similar results were observed with cultured cells obtained from either protocol.Hepatocytes in ‘monolayers’ from both animal groups showed unimpaired proliferative responses with respect to (a) cell multiplication and DNA synthesis rates during an asynchronous 12‐day growth cycle and (b) proliferogenic peptides [insulin, glucagon, and epidermal growth factor (EGF)] that reinitiate DNA synthesis parasynchronously during late stationary phase (days 12–13). Quantitative differences in [3H]leucine uptake into total proteins (cellular plus ‘secreted’) were not detected during the growth cycle. However, during stationary phase (days 8–12), 25%‐75% less [3H]leucine‐labeled albumin was released into culture fluids by hepatocytes from experimental livers than by hepatocytes from control livers. More pronounced differences were seen when albumin in the same culture fluids was measured by radioimmunoassay in contrast to measurements of [3H]leucine‐labeled albumin in these fluids. The defect was reversible since it was not seen in stationary‐phase hepatocyte cultures prepared from rats withdrawn more than 7 days from ethanol treatment whose blood alcohol levels had fallen to 0 mg ethanol/dl.These findings are consistent with the hypothesis that, with respect to albumin production by hepatocytes, chronic ethanol exposure induces a specific but reversible ‘defect’. Because this defect is not seen in short‐term hepatocyte cultures, long‐term cultures should facilitate attempts to understand the molecular and cellular

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1982.tb05383.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY

摘要:

The effect of a single feeding of ethanol on hepatic ornithine decarboxylase (ODC) activity in rats was investigated. Ethanol (7.5 g/kg body weight) was tube‐fed to overnight‐fasted rats as a 50% (v/v) solution in water 1, 2, 3, 4, 8, 12, or 24 hr before sacrifice. The levels of ODC activity in the livers were assayed in vitro by measuring the release of14C02from 0L‐1‐14C‐ornithine. Hepatic ODC activities were significantly stimulated by ethanol (7.5 g/kg body weight) beginning at 1 hr and reaching a peak at 4 hr (more than a 16‐fold increase over zero time controls). Single feedings of varying doses of ethanol (2.5, 5.0, or 7.5 g/kg body weight) to overnight‐fasted rats 3 hr before sacrifice also exhibited significant increases (3 to 13‐fold) in the hepatic ODC activities. In vitro14C‐leucir>e incorporation into protein using hepatic microsomes of ethanol‐treated rats was decreased in comparison with that of controls. The ethanoMnduced stimulation of hepatic ODC activity was not abolished by pretreatment with pyrazoie, an inhibitor of ethanol metabolism. However, the stimulation of hepatic ODC activity by ethanol was suppressed by actinomycin D or cycloheximide, indicating that the enhancement is attributable to the synthesis of new enzyme protein. Furthermore, abolition of the stimulation of hepatic ODC activity due to ethanol by prior adrenalectomy suggests that the induced increase is probably mediated through stimulation of adrenal hormones. These studies demonstrate that a single dose of ethanol per os can significantly enhance in the rat the activity of hepatic ODC, a key enzyyme in the biosynthesis of polyamines, and that the effect is indirect, v

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1982.tb05384.x

出版商:Blackwell Publishing Ltd    

年代:1982

数据来源: WILEY