ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1986.tb05172.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1986.tb05173.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1986.tb05174.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

We have made a comparison between groups of rats fed ethanol and a diet that received intragastric infusion of ethanol continuously for prolonged periods varying only in the amount of fat in the diet (percentage of total calories as fat was 5, 25, and 35%). A fourth group of rats fed high fat (32% of calories) and a diet marginal in protein, vitamins and minerals was also studied. Control rats were pair‐fed dextrose in isocaloric amounts. For rats fed diets containing 5, 25, 32, and 35% fat, the avenge blood alcohol levels achieved were 216,224,266 and 353 mg/100 ml, respectively. Average weight gains of the ethanol fed rats were: 15.4,19.6,14.7, and 14.9 g/week, respectively. Serum alanine aminotransferase (ALT) levels of the ethanol‐fed rats averaged 123,292,144, and 213 units/liter, respectively. ALT levels in pair‐fed controls for the rats fed 32% fat averaged 62 and those of chow‐fed controls averaged 49 units/liter. Comparison of liver biopsy‐semiquantHied morphological findings revealed an increased 3–4+ fatty change in the ethanol‐fed rats also fed the high fat diets: 6/16, 17/17, 5/6, and 5/7 rats, respectively. Necrosis, zonal or spotty, and inflammation were more common in high fat‐fed rats. Moreover, fibrosis was only observed centrilobu‐lariy in rate fed diets with varying fat content (5, 25, 32, or 35% of calories): 0/16,10/17, 4/6, and 3/7 rats, respectively, over a 5‐mon period of feeding. Electron microscopy showed that (to cells predominated in the scarred areas. The mechanism for the centrilobular necrosis‐fibrosis was investigated in rats given a diet of ethanol plus 32% fat diet by measuring the level of adenine nucleotide in repeated liver biopsies in five pairs of rate. There was a significant decrease in liver ATP levels and the total adenylate pool which tended to worsen in serial biopsies over a 4‐mon period of ethanol feeding. Energy change did not decrease. Arterial pOj levels determined in four of these ethanol‐fed rats were reduced compared to controls (83 ± 9,106 ± 9 mm Hg, respectively, p<0.001). The results support the conclusion that rats fed high fat diets and ethanol by continuous intragastric infusion develop centrilobular scarring similar to that seen in baboons and man ingesting ethanol. This implies that a high fat diet may be obligatory for ethanol‐induced Hver fibrosis to develop in the rat Both Ito cell synthesis of collagen and centrilobular hypoxia may be involved in the pathogenesis

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1986.tb05175.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

We have grown HTC cefls (ascites variant of Morris hepatoma 7288c) Hi spinner cultures in the presence of various concentrations of ethanol, both in short‐term incubations and in chronically exposed cultures. In short‐term exposures cell proliferation is decreased in a dose‐related fashion, falling to approximately 25% of control values at 35 mM ethanol. tot reted cultures maintained at ethanol concentrations gradually increased to 17 mM, there is an initial decrease in proliferation followed by stabilization. Comparison of the growth patterns of ceHs chronically exposed to ethanol with the growth patterns of unctoned naive ceHs suggests the presence of both ethanol‐sensitive and ‐resistant HTC cell clones. Preliminary cloning experiments have been successful in demonstrating that HTC clones do exist which have widely varying responses to ethanol. Clones have been isolated which are growth‐inhibited by low concentrations of ethanol whereas others are resistant or even stimulated in the same concentration range. The critical differences between ethanol‐sensitive and ‐resistant HTC cells are currently unknown, but the general phenomenon of clonal selection during chronic ethanol exposure is of interest in the pathogenesis of alcohol

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1986.tb05606.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1986.tb05176.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

Numerous reports dealing with the gross morphological, microanatomies), and behavioral changes occurring with prenatal alcohol exposure in rats have appeared. In order to define the cerebral metabolic correlates of prenatal alcohol exposure, in vivo glucose utilization rates in brain were assayed using an autoradiographic [“CJdeoxygkicose technique. Pregnant Long‐Evans rats were fed liquid diets containing either 35% or 0% ethanol‐derived calories during day 6 through day 20 of gestation. These liquid diets were isocaioric and a pair‐feeding procedure was employed. The offspring were tested on shuttle avoidance techniques at 90 days of age; at 105 days of age all animals were subjected to the deoxyglucose procedures. Prenatal alcohol exposure resulted in a deficit in shuttle avoidance and yielded chronic effects on brain metabolism. Significant decreases in glucose utilization were seen in many structures within sensory, motor, and limbic systems. Significant increases in glucose consumption were found Hi the hypothalamic‐neurohypophysial axis. In summary long‐term behavioral and brain metabolic alterations were seen in rats exposed prenatally

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1986.tb05607.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

Cephalosporin antibiotics with a 1‐methyttetrazofe‐5‐thio side chain have the ability to cause an unpleasant flushing reaction if they are taken some time before the drinking of alcohol. It is proposed that the explanation for this is that the side chain becomes liberatedIn vivoand oxidized to 5,5dithiobis(1‐methyttetrazole) or to a mixed disulfide analogue which then inactivates aldehyde dehydrogenase. Support for this proposal is given by the results below concerning the interactionin vitrobetween the disulfides and sheep Hver cytoplasmic aldehyde dehydrogenase. 5,5Dithiobis(1‐methy!tetrazo!e) has a rapid and pronounced macthratory effect, very similar in many ways (though not identical) to that of disulfiram, to which K has a structural similarity. (Disulfiram is widely used therapeutically to deter alcoholics from drinking.) 1‐Methyl‐5‐methytthiotetrazole (which is a simple model of the antibiotics) and the free 1‐methyfte‐trazole‐5‐thiol have no effect on the enzymein vitro,>but methyl 5‐(1‐methyftetrazoiyl) disulfide is a potent inactivator, this also su

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1986.tb05608.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1986.tb05609.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

ISSN:0145-6008    

DOI:10.1111/j.1530-0277.1986.tb05177.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY