bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sensitivity of Liver Mitochondrial Functions to Various Levels of Ethanol Intake in the Rat
Authors: Quintanilla María Elena , Tampier Lutske 
Published: April 2006

Mitochondrial function appears to be an early target for ethanol toxicity, however it is not clear to what extent the effects of ethanol, which occur at levels of intake lower than those already reported in the literature, can induce an alteration of it. To produce different levels of ethanol intake, the spontaneous consumption of ethanol by genetically low (UChA) and genetically high (UChB) rats, as well as the forced intake obtained by offering 10% v/v ethanol solution as the only source of drinking fluid, were employed.The O2 uptake by liver mitochondria of rats submitted to these conditions in the presence of glutamate + malate, succinate or ascorbate + TMPD, was measured polarographically with a Clark electrode at 25°C. Results indicate that alterations of the hepatic mitochondrial function can be detected at levels of ethanol intake much lower than those previously reported. Whereas, a level of a daily ethanol intake of 2–3 g/kg body weight in UChA rats under free choice was insufficient to produce detectable changes in the mitochondrial function, the latter was decreased in the high ethanol consumers (UChB), which drank 4–5 g/kg per day under free choice conditions, and in both strains forced to drink 10% ethanol as only source of fluid, which produced intakes of about 7 g/kg per day. Therefore, mitochondrial dysfunction may contribute to effects observed even at low levels of ethanol intake.
Laboratory Markers as Compared to Drinking Measures before and after Inpatient Treatment for Alcoholism
Authors: Keso Lauri , Salaspuro Mikko 
Published: April 2006

A study group, consisting of 60 male and 13 female alcohol‐dependent patients, participated in an inpatient treatment for alcoholism. They were interviewed about their alcohol use before the treatment period and bimonthly for 8 months after it.It was found that the correlations between laboratory markers and average daily alcohol intake are very low (range, ‐0.01‐0.23) in alcoholics with high alcoholic intake level (before the treatment period).It was also found that the correlations between the laboratory tests and the drinking measures after the initial assessment undergo large changes. The correlation between GOT and average daily alcohol intake before the treatment period was 0.07 (p= NS) and 2 months after the treatment period 0.55 (p < 0.001). The tong period of abstinence, the change to a lower level of akohd consumption, and improved accuracy of reporting akohd intake were probably causative in this change.GGT proved to have the highest correlations with the drinking measures during the follow‐up and MCV before the treatment period. The frequency measure, number of drinking days, gave consistently higher correlations with the laboratory markers than the measure of drinking amount, average daily alcohol intake.Laboratory markers, GGT and MCV, are well suited for outcome evaluation of drinking behavior of alcoholics after inpatient treatment for alcoholism or other comparative periods of abstinence.
Mechanisms of Alcohol‐induced Suppression of B‐Cell Response
Authors: Aldo‐Benson Marlene 
Published: April 2006

Several investigators have shown that alcohol can suppress the production of antibodies by animals and humans. The studies reported here were designed to determine whether alcohol has a direct effect on the B‐lymphocyte and to determine which stage of the B‐cell response is inhibited by alcohol.B‐lymphocyte lines specific for the antigen dinitrophenyl were used to study the effect of alcohol on the B‐lymphocyte. As little as 100 mg% of alcohol inhibited the response of these pure B‐cell lines to stimulation by either antigen (dinitrophenyl‐Ficoll) or anti‐μ antibody. Since no other cell types were present in the system the suppressive effect was on the B‐cell itself. However, alcohol did not inhibit membrane depolarization induced by antigen crosslinking of immunoglobulin receptors, and it did not inhibit activation of the phosphotidyl inositol pathway by receptor crosslinking.When alcohol was added to antigen stimulated B‐lymphocyte lines for varying periods during the immune response it was found that antibody production was inhibited if 150 mg% alcohol was present from 30 to 48 hr after the antigen was added to lymphocytes. Thirty six to 48 hr is the time required for a stimulated mature B‐lymphocyte to enter the proliferative phase of the immune response. These data raise the possibility that low doses of alcohol can inhibit antigen induced B‐cell proliferation.
Decreased in Vivo Rate of Ethanol Metabolism in the Suckling Rat
Authors: Zorzano Antonio , Herrera Emilio 
Published: April 2006

Blood concentrations of ethanol and acetaldehyde were determined in suckling rats after a single oral ethanol gavage. These results were compared with the hepatic activities of alcohol and aldehyde dehydrogenase. After intragastric administration of 3 g/kg body weight of ethanol, ethanol concentrations were much higher in suckling rats than in adult animals, especially at 90, 120, and 180 min after its administration. In addition, acetaldehyde concentrations were undetectable in suckling rats as opposed to adult rats, in whom micromolar concentrations were detected. Thus, 5‐ to 30‐day‐old rats seem to have a limited capacity for in vivo ethanol metabolism. The analysis of hepatic alcohol dehydrogenase activity revealed that it was very low at birth and it increased progressively with time attaining adult levels after 20 days of life. The alcohol dehydrogenase activity present in the liver of suckling rats presented similar Km values and sensitivity to pyrazole as adult rat liver. Thus, the pattern of in vivo ethanol elimination during the suckling period is not explained by hepatic alcohol dehydrogenase activity. Whether that diminished ethanol metabolism is due to slower intestinal ethanol absorption, different ethanol distribution in the body, or diminished hepatic capacity for NADH reoxidation remains to be studied.At birth, hepatic aldehyde dehydrogenase activity was low and it increased reaching adult levels during the suckling period. Adult levels for the component of low Km were attained earlier than for the component of high Km. The low affinity hepatic aldehyde dehydrogenase component in the newborn was different from that in the adult as assessed by kinetic studies and by its sensitivity to disulfiram. Nevertheless, the fact that acetaldehyde was not detected after ethanol ingestion in suckling rats, suggests that there is enough hepatic aldehyde dehydrogenase activity to metabolize all the acetaldehyde generated in liver by alcohol dehydrogenase.
Hepatic Synthesis of Apoproteins of Very Low Density and High Density Lipoproteins in Perfused Rat Liver: Influence of Chronic Heavy and Moderate Doses of Ethanol
Authors: Lakshman M. R. , Chirtel Stuart J. , Chambers Laura C. , Campbell Barbara S. 
Published: April 2006

The effects of 6 weeks of heavy and moderate ethanol feeding to rats upon lipids and lipoprotein metabolism were determined. As compared to the control group, the heavy ethanol feeding resulted in the following changes: liver weight/kilogram body weight increased by 48% (p < 0.001) with a concomitant 52% increase (p < 0.001) in liver protein/kilogram body weight and a 2.75‐fold (p < 0.001) increase in liver total lipids/kilogram body weight. in contrast, liver DNA/kilogram body weight or per liver was not affected significantly. Plasma cholesterol and triglycerides were higher by 53% (p < 0.01) and 77% (p < 0.01), respectively. Liver cholesterol and triglycerides were 4.4‐fold and 3.6‐fold higher (p < 0.001), respectively. Plasma total A, was 1.72‐fold higher (p < 0.001), whereas there was no significant difference in plasma apo E levels between the two groups. However, plasma high density lipoproteins (HDI) apo E was 48% lower (p < 0.02) while the very low density lipoproteins (VLDL) E was 2.15‐fold higher (p < 0.02).Hepatic total protein synthetic rate in the ethanol group was not significantly different from the control group. In contrast, labeled leucine incorporation into the total secretory proteins was inhibited by 36% (p < 0.01) in ethanol‐fed group. Specifically, inhibitions of the synthetic rates of various secretory proteins in the ethanol group compared to the control group were as follows: by 55% (p < 0.005) for total VLDL apoproteins, by 44% (p < 0.05) for apo A1 protein, by 55% (p < 0.001) for total apo E proteins, by 62% (p < 0.001) for VLDL apo E, by 52% (p < 0.001) for HDL apo E and by 50% (p < 0.001) for transferrin. In contrast, moderate ethanol feeding for six weeks did not alter any of the above parameters. Thus, impaired synthesis/secretion of VLDL and HDL could be the major cause for fatty liver after alcohol abuse.
Prenatal Ethanol Exposure Decreases Hippocampal Mossy Fiber Zinc in 45‐Day‐Old Rats
Authors: Savage Daniel D. , Montano Christine Y. , Paxton Linda L. , Kasarskis Edward J. 
Published: April 2006

The long‐term consequences of prenatal ethanol exposure on histochemically detectable hippocampal mossy fiber zinc was examined using a recently developed quantitative histofluorescence procedure. Pregnant Sprague‐Dawley rats were maintained throughout gestation on one of three dietary regimens: (a) a liquid diet containing either 3.35% ethanol, (b) an isocalorically matched liquid diet pair‐fed to the 3.35% ethanol group, or (c) lab chow ad libitum. At 45 days of age, offspring from each of the three diet groups were sacrificed for determination of hippocampal mossy fiber zinc and zinc analysis of selected tissues by atomic absorption spectroscopy.Hippocampal mossy fiber zinc was reduced by 36% in dorsal and 20% in ventral hippocampal formation stratum lucidum of rats exposed to the 3.35% ethanol diet compared to the offspring of the pair‐fed control and ad libitum control dams. No significant differences in zinc: TS‐Q histofluorescence were observed between the ad libitum and pair‐fed control groups. No significant differences were observed among groups in tissue wet weight or tissue zinc concentration in any of the brain or other body regions analyzed. These results indicate a long lasting prenatal ethanol exposure‐induced reduction in hippocampal mossy fiber zinc in the absence of changes in any indices of total body zinc nutriture. These results suggest that prenatal exposure to relatively low blood ethanol levels (30–40 mg/dl) has subtle, yet long‐lasting effects in the hippocampal formation, a brain region important in the process of memory consolidation.
Protein Synthesis in Bone and Skin of the Rat Are Inhibited by Ethanol: Implications for Whole Body Metabolism
Authors: Preedy Victor R. , Marway Jaspaul S. , Salisbury Jonathan R. , Peters Timothy J. 
Published: April 2006

The acute effects of ethanol (75 mmol/kg body weight, intraperitoneal) on rates of protein synthesis in bone (tibia) and skin of young (approximately 100 g body weight) laboratory rats was investigated. Plasma ethanol levels were raised to approximately 40 mmol/liter. At 2.5 hr, rates of protein synthesis were measured with a flooding dose of L‐[4‐3H]phenylalanine. In bone the protein‐bound specific radioactivities, fractional synthesis rates, and synthesis rates relative to RNA and DNA were significantly reduced by approximately 30%. In skin these variables similarly decreased in response to ethanol treatment, by approximately 25%.The reduction in absolute rates of protein synthesis in bone (Δ, 0.7 g protein/day/kg body weight) and skin (Δ, 3.4 g protein/day/kg body weight) were comparable to the reductions in liver and skeletal muscle in response to acute ethanol. As bone and skin contribute to a quarter of whole body protein synthesis, it was concluded that these observations may have important implications for whole body protein homeostasis.
Alcohol Intoxication Blunts Sympatho‐Adrenal Activation Following Brain Injury
Authors: Woolf Paul D. , Cox Christopher , Kelly Mary , McDonald Joseph V. , Hamill Robert W. 
Published: April 2006

In 46 patients experiencing traumatic brain injury, we studied the interactions of alcohol intoxication and severity of neurologic dysfunction on the resulting sympathetic nervous system activation. Sixty percent of the variation in norepinephrine (p < 0.0001) and more than 50% of the variation in epinephrine (p < 0.0001) were due to the initial ethanol concentrations and extent of brain injury assessed by the admission Glasgow Coma Score (GCS). As brain function deteriorated plasma cathecholamines rose (p < 0.0001), but ethanol qualitatively and quantitatively modified this observation. The magnitude of the sympathetic response to worsening neurologic function was progressively diminished in association with increasing ethanol levels, i.e., the inverse relationship of GCS values with both norepinephrine and epinephrine was flattened. In comatose patients (GCS < B) increasing ethanol levels was associated with progressively decreasing norepinephrine and epinephrine responses (p < 0.04), such that catecholamines were reduced by 80 to 90% at ethanol concentrations approaching 400 mg/dl (87.0 mmol/l). However, the impact of ethanol on the degree of sympathetic nervous system activation depended upon the degree of injury; the apparent ethanol suppression was greatest in patients with the most severe neurologic dysfunction (GCS 3 or 4), but it diminished as neurologic function improved.We conclude that the presence of alcohol appears to modify the rise in catecholamine levels following traumatic brain injury in a dose‐dependent manner and alters the relationship between neurologic dysfunction and SNS activation. These alterations may have profound effects on patient morbidity in the immediate post‐accident period.
Diagnostic Value of Serum γ‐Glutamyl‐Transferase Activity and Mean Corpuscular Volume in Alcoholic Patients with or without Cirrhosis
Authors: Pol Stanislas , Poynard Thierry , Bedossa Pierre , Naveau Sylvie , Aubert Alain , Chaput Jean‐Claude 
Published: April 2006

In an attempt to assess the diagnostic values of serum γ‐glutamyl‐transferase (GGT) and mean corpuscular volume (MCV) variations as markers of liver disease and of abstinence in alcoholic patients, we compared 174 patients with alcoholic cirrhosis, 175 with noncirrhotic alcoholic liver disease and 67 patients with nonalcoholic cirrhosis. GGT and MCV values were checked three times, the day of admission, 7 days later, and on the last sample available during follow‐up (1 to 12 months), and were compared according to the liver disease and abstinence.A decrease of GGT activity during the 1st week of hospitalization was noted in alcoholics with (‐9 IU/liter) or without (‐13 IU/liter) cirrhosis and not in nonalcoholic cirrhosis (+8 IU/liter), without MCV variations. During follow‐up, median GGT activity was strikingly different in abstinent patients with (27 IU/liter) or without (21 IU/liter) cirrhosis and in nonabstinent patients (99 IU/liter and 123 IU/liter, respectively) (p < 0.001). MCV decrease was noted in alcoholics whatever their abstinence or not, contrasting with the absence of decrease in nonalcoholic patients. For the diagnosis of alcoholism in cirrhotic patients, the positive predictive value (PPV) of a GGT or a MCV decrease during the 1st week of hospitalization was 0.82 and 0.78, respectively, and the negative predictive value (NPV) was 0.33 and 0.70, respectively. For abstinence during follow‐up, the PPV of a GGT activity < 50 IU/liter was 0.92 and the NPV was 0.65. In multidimensional stepwise regression analysis, the GGT decrease appeared independently associated with initial GGT activity (p < 0.001) and with alcohol withdrawal (p < 0.001) while MCV decrease was only associated with the initial MCV value.GGT and MCV do appear per se as weak indicators of alcoholism during liver diseases. Inversely, the early decrease of serum GGT activity, which is independent of the type of the liver disease, and a frank decrease of MCV during follow‐up of out‐patients are markers of alcoholism. A persistent decrease of GGT activity to normal or under 2.5‐fold normal values is a marker of abstinence in alcoholics with or without cirrhosis.
Oxysterols and Alcoholic Liver Disease
Authors: Ryzlak Maria T. , Fales Henry M. , Russell William L. , Schaffner Carl P. 
Published: April 2006

A new theory is presented implicating oxidative cholesterol metabolism and oxysterols as possible factors in the development of alcoholic liver disease. Our present studies have revealed the accumulation of cholesta‐3,5‐dien‐7‐one, 13.05 ± 2.75 μg/g (n = 8), and cholesta‐4,6‐dien‐3‐one, 2.26 ± 0.88 μg/g (n = 8) in fatty alcoholic liver, as compared wiht controls, 0.21 ± 0.12 μg/g (n = 7) and 0.3 ± 0.33 μg/g (n = 7), respectively. Acetaldehyde at 1 to 6 micromolar concentration in the blood and tissues of alcoholics cannot account for the extent of tissue damage, nor can it adequately explain liver steatosis characterized by accumulation of cholesterol and fatty acids and their esters in the liver of alcoholics known for their poor dietary habits. Oxysterols may be the primary cause for the development of alcoholic liver diseases and damage to accessory tissues.Significantly lower levels of 7‐ketocholesterol in fatty liver, 6.8 ± 3.5 μg/g (n = 8), as compared with control, 36.85 ± 22.25 μg/g (n = 7), may be responsible for the increased cholesterol content of the alcoholic liver due to the inhibitory properties of this sterol on HMG‐CoA reductase in cholesterol biosynthesis.
Inpatient Treatment of Employed Alcoholics: A Randomized Clinical Trial on Hazelden‐Type and Traditional Treatment
Authors: Keso Lauri , Salaspuro Mikko 
Published: April 2006

The first randomized clinical trial on the Hazelden‐type of treatment showed that this AA‐oriented treatment for alcoholism can result in significant improvement in drinking behavior as compared to a more traditional form of treatment.One hundred forty‐one employed alcoholics were randomized to either Hazelden‐type treatment (N= 74) or to traditional‐type treatment (N= 67). The treatment groups were highly comparable. The bimonthly follow‐up lasted one year.According to the COPES‐questionnaire (short form), the treatment at the Hazelden‐type institute was significantly more involving, supportive, encouraging to spontaneity and oriented to personal problems than at the traditional‐type institute. In accordance the treatment drop‐out rate was 7.9% at Hazelden‐type institute and 25.9% at traditional‐type institute (p < 0.02). The participation in outpatient treatment was significantly better after the Hazelden‐type treatment.The proportion of those abstinent (admitted ethanol consumption, O g/day; gammaglutamyl transferase, and mean cell volume were normal) was higher at Hazelden‐type institute during the last (8–12 months) follow‐up period (26.3% vs. 9.8%, p= 0.05). Fourteen percent of the Hazeldon‐type institute patients and 1.9% of the traditional‐type institute patients stayed abstinent during the whole 1‐year follow‐up period (p < 0.05). The differences for the corresponding rates for controlled drinking (admitted ethanol consumption less than 40 g/day, GGT, and MCV normal) were in the same direction but did not reach statistical significance. Thus the Hazelden‐type treatment obtained better results in 1‐year abstinence rate than a more traditional‐type treatment.
The Potentiating Effects of Ethanol on the Blue Light Depolarization of the Retinal Pigment Epithelium
Authors: Pautler E.L. , Beezley D. 
Published: April 2006

The retinal pigment epithelium (RPE) is the site of two major effects of ethanol. In humans, ethanol produces a slow damped oscillation in the steady electrical potential of the eye, which is generated primarily by the RPE. It has also been shown that ethanol potentiates the reversible, depolarizing effect of blue light on the transepithelial potential (TEP) of the isolated RPE. The present study demonstrates that in addition to the depolarizing effect of blue light on the TEP, a secondary, compensatory potential arises, which functions to maintain the TEP. The magnitude of the secondary response varies somewhat among preparations. It appears that ethanol eliminates or reduces the secondary, compensatory potential change which results in a large depolarization of the TEP when the RPE is irradiated with blue light.Microelectrode studies reveal that ethanol hyperpolarizes both the apical and basal membranes of the RPE with a greater effect noted in the apical membrane. This would account for the corneal positive potential elicited by ethanol in the human eye. Brief exposures (2–3 min) of blue light, after administration of 0.5% ethanol, results in a large (25–30 mV) depolarization of both membrane potentials as compared with 3 to 5 mV in untreated tissue.On the basis of our observations, it is hypothesized that some of the potentiating effects of ethanol in combination with other agents may result from an interference with a cellular adaptive response to impaired respiration rather than an additive effect on a common mechanism.
Pattern and Duration of the Inhibitory Effect of Alcohol Administered Acutely on Suckling‐Induced Prolactin in Lactating Rats
Authors: Subramanian Marappa G. , Chen Xiao Guang , Bergeski Barbara A. 
Published: April 2006

We have characterized the pattern and duration of the inhibitory effect of acute alcohol administration on suckling‐induced prolactin (PRL) release in the lactating rat. On day 2 of lactation, litters were adjusted to eight pups. On day 6, dams were implanted with an atrial catheter and experiments were conducted on day 10 of lactation. Pups were removed from the dams at 0800 hr. An extension tube filled with heparinized saline was attached to the catheter at 1300 hr. At 1400 hr, a preinfusion (PRE 0) blood sample was removed and was followed by infusion of saline (control) or alcohol in saline (0.5, 1.0, 2.0, 2.5 g/kg body weight doses) solutions. Following the removal of a postinfusion (POST 0) blood sample, pups were returned to the mother. Subsequent blood samples were obtained 10, 30, 60, 120, and 180 min after initiation of suckling. In separate groups, the effects of alcohol on basal PRL were studied by collecting blood samples PRE 0, POST 0 and 20,40,60,80,100, and 120 min following infusion of saline or alcohol in saline to lactating rats also separated from their pups for 6 hr.Alcohol infusion did not after basal PRL. However, suckling‐induced PRL was inhibited at 10, 30, 60, and 120 min of suckling by alcohol administered at doses > 1.0 g/kg body weight. After 180 min of suckling, plasma PRL levels were comparable among groups. The suckling latency for the 2.5 g/kg body weight alcohol group was greater than for other groups, but the quantities of milk consumed during the 3‐hr suckling period were comparable. The blood alcohol clearance rates expressed as mg/kg/hr were 220 ± 16, 342 ± 18, and 385 ± 24 for 1.0, 2.0, and 2.5 g/kg/body weight doses, respectively. The growth rate of the pups are judged by the litter weight on days 2, 7, 14, and 21 of lactation, did not differ.The data indicate that alcohol (administered acutely) does not affect the basal plasma PRL in lactating rats. In contrast, suckling‐induced PRL release is inhibited, and this inhibitory effect lasts approximately for 2 hr for the highest alcohol dose (2.5 g/kg body weight) employed. Further, it was also observed that a blood alcohol concentration of 65 mg/dl or greater is necessary to exert the inhibitory effect on suckling‐induced PRL release.