ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1993.tb00717.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Brain lesions in alcoholics are multifactorial in origin. Ethanol neurotoxicity, Wernicke's encephalopathy, hepatocerebral degeneration, head trauma, central pontine myelinolysis, Marchiafava‐Bignami syndrome, pellagra, and premorbid pathological conditions, such as fetal alcohol syndrome, may all contribute to cognitive dysfunction in alcoholics. With the exception of ethanol neurotoxicity, all of these conditions are associated with specific neuropathological lesions. Wernicke's encephalopathy, the neurological syndrome of thiamine deficiency, is frequently overlooked during life and may cause global dementia as well as the more familiar Korsakoff's amnestic syndrome. Distinguishing ethanol neurotoxicity from nutritional deficiency can be facilitated by magnetic resonance imaging, which can visualize some of the specific macroscopic lesions of Wernicke's encephalopathy, central pontine myelinolysis, cerebellar degeneration, and Marchiafava‐Bignami syndrome. Computerized morphometric studies of alcoholic brains have revealed ventricular enlargement, selective loss of subcortical white matter, and alterations in neuronal size, number, architecture, and synaptic complexity. These lesions tend to be more severe when there is coexisting nutritional deficiency or liver disease, suggesting that ethanol neurotoxicity may not be the sole cause. A search for similar lesions in nonalcoholic Wernicke's encephalopathy and nonalcoholic liver disease will help determine the specificity of these lesi

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1993.tb00718.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The mechanisms by which chronic ethanol exposure produces neuronal damage have not been established. Potentially ethanol may reduce normal neurotrophic influences necessary for neuronal survival, growth, and function. We hypothesized that chronic ethanol exposure might produce a decrease in the synthesis, availability, upregulation, delivery, and/or the biological activity of normally occurring neurotrophic factors, or may alter the capacity of target neurons to respond to these factors. The available evidence leading to this hypothesis and supporting data from our laboratory are discussed.

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1993.tb00719.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Hyperexcitability following chronic alcohol exposure appears to result in enhanced activation of glutamatergic synapses in the brain. This enhanced glutamatergic transmission probably results from a combination of increased NMDA receptor activation, decreased GABAAreceptor activation and increased function of voltage‐activated calcium channels. Prolonged or repetitive bouts of enhanced excitatory transmission during withdrawal may destroy central neurons via “excitotoxic” mechanisms. Increased NMDA receptor activation might initiate toxicity by increasing intracellular calcium. Summation of these effects with increased intracellular calcium from voltage‐activated channels might promote disinhibition and enhance cellular damage. Recent studies suggest that NMDA receptor‐initiated excitotoxicity may result from thiamine deficiency. Alterations in neurotransmitter levels and receptor function during alcohol‐related thiamine deficiency may contribute to this neuropathology. Thus, excitotoxic damage due to neural compensation for sustained alcohol levels and nutritional deficits may underlie aspects of alcohol‐related

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1993.tb00720.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Ethanol metabolism in the human brain has been documented to occur with the formation of fatty acid ethyl esters. These neutral lipids can disorder membranes and interrupt mitochondrial function. Their formation is under the control of three synthases, localized to grey matter and purified to homogeneity. cDNA cloning demonstrates two of these enzymes to be GSH S‐transferases and has enabled initiation of genetic studies of alcohol‐induced CNS inj

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1993.tb00721.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1993.tb00722.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The implementation of regulations on access to alcoholic beverages, whether through beverage taxes or restrictions on the availability of this commodity through alcohol outlets, has often been proposed as a legitimate and politically feasible approach to the prevention of alcohol‐related problems. Empirical studies of the effects of these approaches to regulation on alcohol consumption and problems, however, have not been unanimous in their support of these preventive measures. While support exists for the suggestion that increases in alcohol beverage prices reduce consumption and have preventive effects upon the occurrence of problems, relatively little evidence exists for the supposition that the regulation of alcohol availability will have similar preventive effects. The lack of evidence in support of the latter thesis rests primarily upon the difficulty of obtaining sufficient data to examine comprehensive models of access to alcohol.The current paper analyzes aggregate time series cross‐sectional data from states of the U.S. to evaluate the relationships between alcohol beverage prices, availability, and alcohol sales within one analytic model. The model relates beverage prices and alcohol availability directly to alcohol sales in the context of an assumed simultaneous relationship between sales and availability. The results show that, independent of the effects of beverage prices, and controlling for the endogeneity of sales and availability, physical availability of alcohol was directly related to sales of spirits and w

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1993.tb00723.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1993.tb00724.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

We have studied the factors determining the rate of ethanol and acetaldehyde metabolism in a group of 25 alcoholics with varying degrees of liver lesion (from normal liver to cirrhosis) and in six nonalcoholic cirrhotics. In alcoholics the ethanol metabolic rate was related to hepatic function, estimated either by the aminopyrine breath test (r= 0.70,p<0.001) or the indocyanine green clearance (r= 0.76,p<0.01), and was independent of the activity of hepatic alcohol dehydrogenase and hepatic blood flow. In nonalcoholic cirrhotics blood acetaldehyde was always below the detection limit (0.5 μM), but elevated levels were found in 14 out of the 25 alcoholics. Alcoholics with elevated blood acetaldehyde showed a significantly higher ethanol metabolic rate than alcoholics with undetectable acetaldehyde (120 ± 17 mg/kg/hr vs 104 ± 11 mg/kg/hr,p<0.02), but no differences were observed in the activities of alcohol and aldehyde dehydrogenases. Peak blood acetaldehyde levels were directly related to the ethanol metabolic rate (r= 0.48,p<0.02), but not to activities of hepatic alcohol or aldehyde dehydrogenases. These results indicate that in chronic alcoholics the main determinant of the ethanol metabolic rate is hepatic function, while the rise of blood acetaldehyde is mainly dependent on the ethanol metabolic rate. Alcohol and aldehyde dehydrogenase activities do not seem to be rate‐limiting factors in the oxidation of ethanol or acetalde

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1993.tb00725.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Excessive or prolonged stimulation of,N‐methyl‐D‐aspartate (NMDA) receptors appears to play an important role in many neurodegenerative processes in brain through a process known as excitotoxicity. This study examined the effects of ethanol on NMDA receptormediated excitotoxicity in primary neuronal cultures obtained from embryonic rat whole brain. Neurotoxicity was quantitated by measuring the amount of lactate dehydrogenase released into the media during a 20‐hr time period following NMDA washout. Exposure of 12‐to 14‐day‐old cultures to NMDA in Mg2+‐free HEPES buffer (pH 7.4) for a 25‐min period resulted in a concentration‐dependent toxicity (EC50= 54 μM). Time‐course experiments showed that exposure to NMDA for as little as 5 min was excitotoxic and reached a plateau after a 20‐min exposure period. Preincubation of the cultures with ethanol (25 to 200 mm) resulted in a concentration‐dependent inhibition of NMDA‐mediated toxicity with approximately 38% inhibition produced by 25 mm ethanol and essentially complete inhibition at 200 mm ethanol (IC50= 60 mm). Increasing the glycine concentration to 100 μM did not potentiate NMDA neurotoxicity or antagonize the neuroprotective effect of ethanol. NMDA‐Mediated excitotoxicity was reduced by approximately 50% by the glycine antagonist 7‐chlorokynurenate (50 μM). Ethanol (50 mm) reduced NMDA neurotoxicity similar to 7‐chlorokynurenate, and the two together produced greater inhibition than either alone. These results show that intoxicating concentrations of ethanol can potently inhibit NMDA receptor‐mediated excitotoxicity and may have important implications in terms of ethanols interactions with brain trauma, ischemia, and other neuropathologies associated wit

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1993.tb00726.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY