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Biomedical subjects

C S Lieber

Publications and source records attributed to C S Lieber.

At least 127 records · Page 7Linked to original sources
PubMed1993

Ethanol metabolism in deermice: role of extrahepatic alcohol dehydrogenase.

The relative contributions to ethanol metabolism of extrahepatic alcohol dehydrogenase (ADH) and of liver microsomes were assessed in deermice, which lack hepatic low Km ADH (ADH-). In vitro kinetic studies showed the existence of high Km (> 1 M) ADH activity in the liver and kidney, and an enzyme with intermediate Km in the gastric mucosa (Km = 133 mM), whereas the low Km ADH was missing. With deuterated ethanol, ADH- deermice showed a significant exchange of reducing equivalents that had been equated with ethanol metabolism by others, whereas we found a poor correlation between the rate of exchange and the rate of metabolism. In vitro studies with subcellular fractions, isolated hepatocytes, and tissue slices revealed that neither liver, nor kidney, nor stomach from ADH- deermice contributed to exchange of reducing equivalents. These findings clearly indicated that the ADHs with high or intermediate Km of the tissues studied are not responsible for the exchange. Furthermore, gastrectomized ADH- deermice still showed an exchange of reducing equivalents, thereby dissociating exchange from gastric ADH activity. Moreover, pretreatment with cimetidine (50 mg/kg body weight), an inhibitor of gastric ADH, did not alter the rate of total ethanol elimination when ethanol was given intraperitoneally. In conclusion, when ethanol was given parenterally, the microsomal ethanol-oxidizing system rather than gastric ADH is a major pathway of ethanol oxidation in ADH- deermice, whereas both pathways contribute significantly to the metabolism of orally administered ethanol.

Alcohol Dehydrogenase↗
PubMed1993

First-pass metabolism of ethanol is predominantly gastric.

Oral consumption of alcohol results in much lower blood alcohol concentrations (BACs) than does the same dose administered intravenously, suggesting significant first-pass metabolism (FPM). The questions remain, however, (1) whether this difference truly represents FPM or simply reflects slower absorption of alcohol, and (2) if there is FPM, is it mainly of gastric or hepatic origin. To study this, rats were given the same dose alcohol (1 g/kg) by either intragastric intubation or by intravenous, intraportal, and intraduodenal infusions at a rate that mimicked the loss of alcohol from the stomach. Higher BAC levels after intravenous than intragastric alcohol indicated true FPM. Higher levels after intraportal or intraduodenal infusions (in fact, comparable to those obtained with the intravenous route) demonstrated negligible FPM when the route of delivery bypassed the stomach, yet included the liver. Furthermore, rats that had developed portosystemic shunts after ligation of the portal ven exhibited blood alcohol curves and FPM equivalent to those of sham-operated controls, indicating that FPM is not dependent on first-pass flow through the liver, but reflects gastric metabolism. The absence of significant hepatic FPM is attributable to the saturation of hepatic alcohol dehydrogenase by recirculating alcohol, resulting in no appreciable increase in metabolism secondary to newly absorbed alcohol. Finally, the in vivo gastric metabolism of alcohol in pylorus-ligated rats was demonstrated by significantly lower BACs when alcohol was administered intragastrically than when an amount identical to that lost from the ligated stomach was given intraportally. Thus, the lower BACs with oral as opposed to intravenous alcohol are not simply a consequence of slow absorption, but result from FPM occurring predominantly in the stomach.

Alcohol Dehydrogenase↗
PubMed1993

Comparison of new methods for measuring carbohydrate-deficient transferrin (CDT): application to a public health approach for the prevention of alcoholic cirrhosis.

Recently, Xin et al. (1991) developed an isoelectric focusing/Western blot (IEF/WB) procedure for serum CDT measurement which compares favorably with the micro anion-exchange chromatography/radioimmunoassay technique of Stibler et al. (1986). The latter is now marketed in a modified version (Stibler et al., 1991), gives values that correlate with those of IEF/WB but are nearly 5-fold lower, with significantly lesser sensitivity for detecting recent drinkers; these are also less well discriminated from non-drinking patients with liver disease. We are now able to screen for heavy drinking using IEF/WB. Some of the complications of liver disease are then detected with standard liver function tests. Next we need to detect precirrhotic lesions (perivenular and/or perisinusoidal fibrosis) which, at present, requires a liver biopsy. These patients--at high risk to rapidly develop cirrhosis upon continuation of drinking--should be subjected to intensive treatment, instituted prior to their medical or social disintegration, with the goal to prevent progression to cirrhosis.

Alcohol Drinking↗
PubMed1993

Alcohol consumption enhances fatty acid omega-oxidation, with a greater increase in male than in female rats.

Because ethanol inhibits mitochondrial fatty acid oxidation, with substantial accumulation of fatty acids in the livers of female (but not male) rats, and induces microsomal activities, we assessed possible changes in omega-oxidation. To study this, we pair-fed 24 male and 24 female littermate rats of the same age liquid diets containing 36% of energy either as ethanol or as additional carbohydrate for 4 wk. In controls, the microsomal omega-hydroxylation of lauric acid was 28% greater in female than in male rats (p < 0.05). Ethanol feeding significantly increased this activity in both genders (p < 0.01), but the rise in male rats (89%) was significantly higher than that in female rats (24%). This activity was unaffected by the presence of ethanol in the assay. The effects of ethanol were associated with increases in the content of cytochrome P-450 4A1 (as assessed in Western blots by the reactivity against a sheep antibody against P-450 4A1), and more so in male than in female rats. Despite possible competition by ethanol with the hydroxy fatty acid oxidation to dicarboxylic acids through alcohol dehydrogenase, suberic and sebacic acids accumulated significantly in the livers of alcohol-fed male rats. These effects of ethanol and gender on omega-oxidation paralleled those on the hepatic cytosolic fatty acid-binding protein and fatty acid esterification previously reported in similarly treated rats. Dicarboxylic acid products of omega-oxidation have been incriminated as mediators of similar effects by other drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Effects of ethanol on prostanoid production by liver fat-storing cells.

Fat-storing cells participate in the development of alcoholic liver disease. To study possible effects of ethanol on prostaglandin metabolism by fat-storing cells, we isolated them from normal rat liver. Cultured fat-storing cells produced substantial amounts (DNA, about 2 ng/micrograms every 24 hr) of prostaglandin E2 and prostaglandin I2 (measured as 6-keto prostaglandin F1 alpha) but no significant amounts of prostaglandin F2 alpha. This production was markedly enhanced by the addition of ethanol in concentrations likely to occur in the blood during alcohol consumption. We confirmed the presence of class 1 alcohol dehydrogenase activity and isoenzymes in the cytosol of cultured fat-storing cells in their second passage. The stimulatory effect of ethanol was inhibited by 4-methylpyrazole (an alcohol dehydrogenase inhibitor), exaggerated by disulfiram (an aldehyde dehydrogenase inhibitor) and reproduced by concentrations of acetaldehyde likely to occur in the liver. Thus, our results indicate that fat-storing cells produce vasodilatory prostaglandins and that this production is enhanced by the acetaldehyde that results from the oxidation of ethanol catalized by alcohol dehydrogenase present in these cells.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Acetaldehyde adducts and autoantibodies against VLDL and LDL in alcoholics.

Alcohol consumption markedly increases the hepatic output of very low density lipoprotein (VLDL), whereas it decreases the resulting low density lipoprotein (LDL) levels and apolipoprotein B. As ethylation of apoB-lysine renders LDL immunogenic and accelerates their clearance, and as alcoholics develop antibodies against acetaldehyde-protein adducts, we searched for antibodies against lipoproteins. We measured serum IgG, IgA, and IgM titers against VLDL, LDL and high density lipoprotein (HDL) in 10 non-alcoholics and 35 recently drinking alcoholics by ELISA assay. Alcoholics had higher IgG titers than non-alcoholics against VLDL and LDL; these were higher with VLDL than LDL or HDL. Using VLDL and LDL (but not HDL) from alcoholics gave the greatest response. There was no difference in IgA and IgM reactivity. To search for acetaldehyde adducts, we measured the reactivity of VLDL, LDL, HDL, and residual serum proteins against a rabbit anti P4502E1-acetaldehyde adduct IgG, which recognizes the adducts but not the unmodified proteins (except for P4502E1). ApoB-containing lipoproteins from alcoholics (and to a lesser extent non-lipoprotein proteins) reacted with anti-adduct IgG more strongly than those of non-alcoholics. The difference was striking for VLDL, less for LDL, and not detectable for HDL. This suggests that acetaldehyde reacts with apoB prior to its secretion from the liver and that the altered VLDL are partially removed prior to their conversion to LDL. In conclusion, alcoholics develop acetaldehyde adducts in apoB-containing lipoproteins, particularly VLDL. The immune response to these neoantigens could result in accelerated clearance of VLDL and LDL and decreased conversion of VLDL to LDL.

Acetaldehyde↗
PubMed1993

Induction of cytochrome P-4502E1 in the human liver by ethanol is caused by a corresponding increase in encoding messenger RNA.

The propensity of centrilobular liver damage to develop in alcohol abusers after exposure to various hepatotoxins, including ethanol itself, has been linked to the induction by ethanol of P-4502E1, a microsomal P-450 enzyme that bioactivates these agents to reactive metabolites. Whereas long-term ethanol consumption elicits a marked increase in hepatic P-4502E1 content, the molecular mechanism by which ethanol produces this effect is the subject of controversy in animals, and it has not been elucidated in human beings. Possible mechanisms include increased enzyme synthesis stemming from elevated 2E1 messenger RNA levels, enhanced translation of preexisting messenger RNA or stabilization of P-4502E1 protein. To determine which, if any, of these mechanisms underlies P-4502E1 induction in human beings, we examined the effects of ethanol intake on the hepatic intralobular distribution of P-4502E1 messenger RNA and the corresponding protein. Liver sections derived from needle biopsy specimens were obtained from five recently drinking alcoholics (last drink no more than 36 hr before) and eight control subjects (five abstaining alcoholics [last drink 96 hr or more before] and three nondrinkers). In situ hybridization of these liver sections with a human P-4502E1 complementary DNA probe was used to localize P-4502E1 messenger RNA transcripts. Quantitative image analysis of hybridized sections from control subjects revealed that P-4502E1 transcript content in perivenular (zone 3) hepatocytes was significantly higher (p < 0.05) than in midzonal (zone 2) and periportal (zone 1) cells (18.3 +/- 1, 9.5 +/- 2 and 3.1 +/- 2 arbitrary density units, respectively; mean +/- S.E.M.). In recent drinkers, acinar regions containing P-4502E1 transcripts were elevated 2.9-fold compared with those in controls (32.8% +/- 7% vs. 11.2% +/- 2%; p < 0.01), with this messenger RNA increase occurring mainly in perivenular cells (29.6 +/- 3 vs. 18.3 +/- 1 units; p < 0.01). P-4502E1 protein distribution, assessed by the immunohistochemical staining of liver sections with P-4502E1 antibodies, was found to be analogous to that of the messenger RNA in control subjects (the level in perivenular cells was greater than that in midzonal cells, which was greater than that in periportal cells), whereas recent drinkers exhibited marked elevations in enzyme content in both perivenular and midzonal hepatocytes. Moreover, cellular levels of P-4502E1 protein and messenger RNA were significantly correlated (rs = 0.79; p < 0.001) in all patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1993

Acetaldehyde-collagen adducts in N-nitrosodimethylamine-induced liver cirrhosis in rats.

Increased acetaldehyde levels have been found in non-alcoholic liver diseases and an acetaldehyde-collagen adduct has been reported in rats with CCl4-induced cirrhosis. In cytosol and microsomes of rats with cirrhosis produced by N-nitrosodimethylamine, a similar acetaldehyde-protein adduct of approximately 200 kD was recognized by rabbit IgG raised against either an in vitro produced hemocyanin-acetaldehyde adduct or an in vivo occurring P4502E1-acetaldehyde adduct isolated from alcohol-fed rats, as well as by anti-rat collagen (I) IgG. Its immune complexes contained 3 proteins that reacted with the anti-collagen IgG and were digested by collagenase: 2 proteins with molecular weights similar to procollagens alpha 1 and alpha 2, and a beta 1,2(I)-like protein which was readily produced by in vitro modification of cytosol with acetaldehyde.

Acetaldehyde↗
PubMed1993

Differential depletion of carotenoids and tocopherol in liver disease.

Carotenoids and tocopherols are major natural protective agents against free radical-mediated liver damage, but their levels in diseased liver are largely uncharted. Therefore we carried out measurements with high-pressure liquid chromatography of alpha- and beta-carotene, lycopene, cryptoxanthin, lutein and zeaxanthin, total retinoids and alpha- and gamma-tocopherol. Liver tissue was obtained from percutaneous needle biopsies, livers of transplant recipients or a donor bank. Compared with controls (transplant donors; n = 13), levels of all carotenoids and retinoids were extremely low at all stages of liver disease. Patients with alcoholic cirrhosis (n = 11) had 20- and 25-fold decreases of levels of lycopene (p < 0.001) and alpha- and beta-carotene (p < 0.005), respectively. Even in subjects with less severe alcoholic liver disease (steatosis, perivenular fibrosis, portal fibrosis; n = 14) and in patients with nonalcoholic liver disease (n = 13), levels were four to six times lower than those in normal subjects. By contrast, levels of alpha-tocopherol were decreased significantly only in patients with cirrhosis, who displayed a threefold reduction. In the serum of most patients, lycopene and tocopherol concentrations were not depressed, whereas one third of alpha- and beta-carotene levels were low, probably reflecting poor dietary intake. A significant correlation was observed between serum and liver alpha- and beta-carotene levels (p < 0.0001; r = 0.715). However, of the patients with extremely low liver alpha- and beta-carotene concentrations, more than half had blood levels in the normal range, suggesting that liver disease interferes with the uptake, excretion or, perhaps, metabolism of alpha- and beta-carotene. In the cirrhotic livers of eight candidates for liver transplantation, the ratios of alpha- and beta-carotene to total retinoids and of beta-carotene to retinoids were much higher than those in normal livers, suggesting some impairment in the conversion of alpha- and beta-carotene to retinoids. In most cases, even with high ratios, absolute levels of hepatic alpha- and beta-carotene and retinoids were severely depressed. We concluded that, even in the presence of normal serum levels alpha- and beta-carotene, tocopherol and lycopene, patients with cirrhosis have extremely low hepatic levels.

Adult↗
PubMed1992

Retinol forms retinoic acid via retinal.

Hepatic cytosol from normal deermice having cytosolic alcohol dehydrogenase (ADH+) also displays retinol dehydrogenase activity and converts retinol to retinoic acid, whereas cytosol from ADH- deermice lacks these enzyme activities and does not produce retinoic acid. Furthermore, microsomes from either strain do not convert retinol to retinoic acid. However, when cytosol from ADH- animals is added to the microsomes, retinoic acid is produced. The obligatory role of retinal as an intermediary step in retinoic acid formation is further shown by isotopic dilution of retinoic acid formed from labeled retinol upon addition of unlabeled retinal. Microsomal retinol dehydrogenase also catalyzes the reduction of retinal to retinol, thereby explaining the decrease in retinoic acid production from retinol in liver cytosol of ADH+ deermice when microsomes are added. Thus, the results of this study indicate that retinal is an obligatory intermediate in the hepatic production of retinoic acid from retinol and that cytosolic and microsomal retinol dehydrogenases play a key role in this process.

Alcohol Dehydrogenase↗
PubMed1992

Effects of ranitidine on blood alcohol levels after ethanol ingestion. Comparison with other H2-receptor antagonists.

OBJECTIVE: To determine whether the H2-receptor antagonist, ranitidine, which is a potent inhibitor of gastric alcohol dehydrogenase activity in vitro, increases the bioavailability of orally administered ethanol (0.3 g/kg of body weight) and to compare the resulting blood alcohol concentrations with those of two other H2-antagonists, cimetidine and famotidine, the latter of which does not inhibit gastric alcohol dehydrogenase. DESIGN: For each of the H2-receptor antagonists, a different group of subjects was used. In each group, a paired design was adopted with each subject serving as his own control. SETTING: Hospital laboratory. SUBJECTS: Normal, healthy men aged 24 to 46 years. INTERVENTION: Eight men were treated for 1 week with ranitidine (300 mg/d), six with cimetidine (1000 mg/d), and six with famotidine (40 mg/d). MEASURES: Peak blood alcohol concentrations, areas under the blood alcohol curve, first-pass metabolism, and bioavailability of orally consumed ethanol. RESULTS: Relative to baseline, ranitidine increased the mean peak concentration and the area under the curve of blood alcohol concentrations by 34% (P less than .05) and 41% (P less than .01), respectively. First-pass metabolism of ethanol was decreased from 70 +/- 10 to 31 +/- 9 mg/kg of body weight, with a corresponding increase in ethanol bioavailability of 79.6% to 92.6%. By comparison, cimetidine had even a greater effect on blood alcohol levels, while famotidine had no significant effects. CONCLUSION: Patients treated with ranitidine or cimetidine should be warned of possible functional impairments after consumption of amounts of ethanol considered safe in the absence of such therapy.

Adult↗
PubMed1992

Polyunsaturated lecithin prevents acetaldehyde-mediated hepatic collagen accumulation by stimulating collagenase activity in cultured lipocytes.

We recently found that polyunsaturated lecithin prevents ethanol from causing cirrhosis in the baboon. Because transformation of lipocytes to transitional cells plays a key role in hepatic fibrogenesis in vivo, and because this process in alcohol-fed baboons was found to be attenuated by polyunsaturated lecithin, we focused on lipocytes to study the mechanism of the protective effect. Rat lipocytes cultured on plastic undergo spontaneous activation, accompanied by expression of alpha-smooth muscle actin isoform and production of substantial amounts of type I collagen. The latter was further increased on incubation with acetaldehyde. This in vitro model was used here to study how acetaldehyde-mediated collagen production and accumulation can be turned off. Addition of polyunsaturated lecithin (10 mumols/L) was found to prevent the acetaldehyde-induced increase in collagen accumulation by 83% (p less than 0.001). By contrast, a saturated phospholipid (10 mumols/L dilauroyl phosphatidylcholine), a monounsaturated one (10 mumols/L linoleoyl-palmitoyl phosphatidylcholine) or linoleic acid (20 mumols/L bound to albumin) had no such effect. Incorporation of [3H]proline into collagen and the expression of alpha-1 (I) procollagen mRNA were increased by acetaldehyde; the latter was not significantly affected by polyunsaturated lecithin. Polyunsaturated lecithin increased lipocyte collagenase activity by 100% (p less than 0.001), whereas dilauroyl phosphatidylcholine, linoleoyl-palmitoyl phosphatidylcholine and linoleic acid had no such action. We concluded that (a) polyunsaturated lecithin selectively prevents the acetaldehyde-induced increase in collagen accumulation in lipocyte cultures, whereas other phospholipids or linoleate have no such effect; and (b) polyunsaturated lecithin does not modify the acetaldehyde-mediated increase in alpha-1 (I) procollagen mRNA, but it increases collagenase activity, suggesting that the protective effect exerted by polyunsaturated lecithin against alcohol induced fibrosis in vivo is due at least in part to stimulation of collagenase activity, which may prevent excess collagen accumulation by offsetting increased collagen production.

Acetaldehyde↗
PubMed1992

Interaction of ethanol with beta-carotene: delayed blood clearance and enhanced hepatotoxicity.

Because we had found that ethanol interacts with retinol, we investigated whether it also affects its precursor, beta-carotene. In 14 baboons fed ethanol (50% of total energy) for 2 to 5 yr with a standard amount of beta-carotene (one 200-gm carrot/day), levels of beta-carotene were much higher than in controls fed isocaloric carbohydrate, both in plasma (122.5 +/- 30.9 nmol/dl vs. 6.3 +/- 1.4 nmol/dl; p less than 0.005) and in liver (7.9 +/- 1.1 nmol/gm vs. 1.8 +/- 0.5 nmol/gm; p less than 0.001). Even 20 days after withdrawal of the carrots, plasma beta-carotene levels remained higher in alcohol-fed baboons than in controls (10.1 +/- 3.8 nmol/dl vs. less than 0.1 nmol/dl). Next, the diet was supplemented with beta-carotene beadlets: in four pairs of baboons given a low dose of beta-carotene (3 mg/1,000 kcal), plasma levels were significantly higher in alcohol-fed animals than in controls, even when expressed per cholesterol (although the latter increased with alcohol intake). Seven pairs of animals were given a higher dose (30 mg/1,000 kcal) of beta-carotene for 1 mo, followed, in four pairs, by 45 mg for another month. On cessation of beta-carotene treatment, plasma levels decreased more slowly in the alcohol-fed baboons than in the controls. Percutaneous liver biopsy specimens revealed that liver concentrations of beta-carotene correlated with plasma levels but were higher in the alcohol-fed baboons than in the control baboons, whereas the beta-carotene-induced increase in liver retinoids was lower (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effect of omeprazole on gastric first-pass metabolism of ethanol.

Some commonly used H2-receptor antagonists affect gastric first-pass metabolism of ethanol and lead to unexpectedly high blood alcohol concentrations after consumption of alcohol. To investigate whether omeprazole--a substituted benzimidazole recently approved for clinical use--has a similar harmful effect, we administered a moderate dose of ethanol (0.3 g/kg body wt) orally to seven normal volunteers before and after one week of omeprazole administration (20 mg daily). No significant effect of the drug was found on either mean peak blood alcohol concentrations or on areas under the blood alcohol curve; neither did these parameters differ significantly before or after an acute dose of omeprazole (13.2 mg/kg body wt) in rats, whether ethanol (0.25 g/kg body wt) was administered intragastrically or intravenously. In vitro, omeprazole in concentrations likely to occur in the gastric lumen (0.01-1.0 mM), did not affect gastric alcohol dehydrogenase activity of humans or rats. Thus omeprazole does not affect gastric first-pass metabolism of ethanol and can be considered as a safe choice for the treatment of patients who do not refrain from alcohol consumption during therapy.

Adult↗
PubMed1992

Uridine diphosphoglucose restores lipocyte proliferation in the regenerating liver of ethanol-treated rats.

The effect of continuous intraperitoneal infusion of uridine diphosphoglucose on ethanol-induced suppression of lipocyte proliferation was studied in regenerating rat livers from 1-4 days after hepatectomy. Proliferating lipocytes were positively identified using a two-sequence immunohistochemical staining for cytoplasmic desmin and bromodeoxyuridine-labelled nuclei. Hepatectomy rapidly stimulated lipocyte proliferation which peaked 2 days after hepatectomy (labelling index, 17.9 +/- 0.81%). uridine diphosphoglucose or glucose infusion did not modify the time course of lipocyte proliferation. Ethanol feeding to hepatectomized rats receiving saline or glucose infusion resulted in a 71% (p less than 0.005) and 61% (p less than 0.005) inhibition of lipocyte proliferation, respectively, 2 days after hepatectomy, thereby abolishing the characteristic proliferative peak observed in rats not treated with ethanol. In contrast, uridine diphosphoglucose infusion doubled the labelling index (13.1 +/- 2.34%) in ethanol-fed rats compared to that in corresponding rats treated with saline (5.28 +/- 1.29%; p less than 0.005) or glucose (6.51 +/- 0.64%; p less than 0.005). This resulted in the appearance of a proliferative peak, albeit smaller than normal, 2 days after hepatectomy. In sham-operated rats, lipocyte proliferation was low with a labelling index of 1.88 +/- 0.13% at the time of operation and of 1.69 +/- 0.23% 2 days thereafter. Uridine diphosphoglucose infusion to sham-operated rats for 2 days did not significantly affect lipocyte proliferation (labelling index 1.79 +/- 0.06%). The present study demonstrated that uridine diphosphoglucose does not affect lipocyte proliferation in the regenerating or sham-operated livers, but that it partially reverses the ethanol-induced suppression of lipocyte proliferation after hepatectomy.

Analysis of Variance↗
PubMed1992

Human immunodeficiency virus and hepatitis B virus infections in a New York City alcoholic population.

Alcoholics have previously been reported to have an increased susceptibility to hepatitis B virus (HBV) infection. Since human immunodeficiency virus (HIV) is transmitted in a similar fashion, we studied 143 consecutive in- and outpatient alcoholics residing in New York City for HIV and HBV prevalence and associated risk factors. Of these alcoholics, 19 (13%) individuals were HIV positive, 57 (40%) were hepatitis B seropositive. Intravenous drug use and sexual contact with an IV drug user were the most important risk behaviors for HIV acquisition, with large numbers of partners and anal heterosexual intercourse being lesser factors. The only significant risk behavior determined for hepatitis B infection was IV drug use. These high-risk behaviors did not appear to be related to episodes of alcoholic intoxication. However, it is conceivable that alcoholism may, in other ways, affect susceptibility to HIV infection.

Adult↗
PubMed1992

Measurement of carbohydrate-deficient transferrin by isoelectric focusing/western blotting and by micro anion-exchange chromatography/radioimmunoassay: comparison of diagnostic accuracy.

At present, the most reliable marker of recent and heavy alcohol intake is carbohydrate-deficient transferrin (CDT). While most CDT quantitation methods (including immunofixation and micro anion-exchange chromatography [MAEC] combined with radioimmunoassay [RIA]) either lack the precision required for diagnostic usage or are not commercially available, we recently described an isoelectric focusing/Western blotting (IEF/WB) procedure that provides sensitive and specific assessment of serum CDT content. However, a modified MAEC/RIA kit, supposedly more reliable than the original, is also being advanced as suitable for widespread clinical application. Therefore, we compared this modified MAEC/RIA procedure to the IEF/WB method of CDT quantitation in the following 108 subjects; 53 alcoholics undergoing detoxification without clinical or histological evidence of liver disease, 24 recently drinking alcoholics with biopsy-proven liver disease, eight alcoholics abstinent for more than 30 days with biopsy-proven liver disease, seven non-drinking patients with non-alcoholic liver disease, and 16 healthy controls. Although CDT measurements by the two methods were correlated (r = 0.60, P < 0.01), serum CDT values obtained with IEF/WB were nearly five-fold higher than those obtained with MAEC/RIA (e.g. 140.0 +/- 58 versus 28.5 +/- 16 mg/l among the active drinkers). Of the two methods, IEF/WB exhibited significantly greater sensitivity than MAEC/RIA for detecting recent, heavy drinking (75% versus 61%, P < 0.05) and generated no false positives whereas MAEC/RIA gave falsely elevated CDT levels in 37% of the abstinent alcoholics.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗