2024-03-28T17:42:44Zhttp://open-archive.highwire.org/handler
oai:open-archive.highwire.org:alcalc:39/2/1012015-05-19HighWireOUPalcalc:39:2
BRAIN NITRIC OXIDE SYNTHASE LEVELS INCREASE IN RESPONSE TO ANTENATAL ETHANOL EXPOSURE
Dizon, Maria L. V.
Brown, Lou Ann
Black, Stephen M.
ORIGINAL ARTICLES
<b>Aims:</b> Our previous <it>in vitro</it> data have indicated that ethanol can increase nitric oxide synthase (NOS) expression. Thus, the Aims of this study were to determine whether ethanol produces the same effect <it>in vivo</it>. <b>Methods:</b> To accomplish this, we utilized the well-established prenatal ethanol (EtOH) exposure model in the guinea pig to examine the effect on brain NOS expression and activity. <b>Results:</b> Brain homogenates isolated from offspring of guinea pigs fed EtOH exhibited an increase in NOS protein expression and NOS activity compared to controls. Increased expression of neuronal NOS was observed only in soluble fractions of brain homogenates (<it>P</it> < 0.05 vs. control). Increased expression of a ∼60 kDa band was detected in the soluble fraction that was immunoreactive against an antiserum raised against inducible NOS. In addition, an immunoreactive band of the correct predicted molecular weight for iNOS was found in the particulate fraction although the expression was unchanged between control and EtOH-treated animals. Endothelial NOS protein expression could not be detected in either soluble or particulate fractions from control or EtOH-treated animals. <b>Conclusions:</b> These results suggest that EtOH may exert its toxic effects antenatally via a mechanism of altered nitric oxide availability from NOS.
Oxford University Press
2004-03-01 00:00:00.0
TEXT
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http://alcalc.oxfordjournals.org/cgi/content/short/39/2/101
http://dx.doi.org/10.1093/alcalc/agh032
en
Copyright (C) 2004, Medical Council on Alcohol
oai:open-archive.highwire.org:alcalc:39/2/1062015-05-19HighWireOUPalcalc:39:2
BINGE DRINKING AND NITRIC OXIDE METABOLITES IN CHRONIC LIVER DISEASE
Oekonomaki, Eleni
Notas, Georgios
Mouzas, Ioannis A.
Valatas, Vasilios
Skordilis, Panagiotis
Xidakis, Constantinos
Kouroumalis, Elias A.
ORIGINAL ARTICLES
<b>Aims:</b> The effect of binge drinking in the production of nitric oxide metabolites has not been studied in patients with chronic viral liver disease. <b>Methods:</b> We therefore studied serum levels of nitrites and nitrates (NOx) in 13 patients with chronic viral hepatitis and nine patients with compensated viral cirrhosis, after administration of 80 g alcohol. 15 patients with compensated alcoholic cirrhosis and seven healthy individuals were used as controls. Serum NOx levels were measured by a modification of the Griess reaction before and at 2, 12 and 24 h after alcohol consumption. <b>Results:</b> An increase of serum NOx levels, that was statistically significant at 12 h, was found in healthy controls (<it>P</it> < 0.05). A similar pattern of NOx levels was observed in patients with chronic hepatitis. By contrast, in patients with cirrhosis, either viral or alcoholic, no significant increase was found after alcohol administration. However, basal levels in cirrhotics were significantly elevated (82.2 ± 13.8 vs. 43.1 ± 7.2 µmol/l, <it>P</it> < 0.01) compared to healthy controls. <b>Conclusions:</b> Binge drinking causes a significant increase of serum NOx evident after 12 h with a return after 24 h at pre-drinking levels in healthy controls and patients with chronic viral hepatitis. In cirrhosis, such an increase is not observed serum levels being constantly elevated throughout the study period.
Oxford University Press
2004-03-01 00:00:00.0
TEXT
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http://alcalc.oxfordjournals.org/cgi/content/short/39/2/106
http://dx.doi.org/10.1093/alcalc/agh030
en
Copyright (C) 2004, Medical Council on Alcohol
oai:open-archive.highwire.org:alcalc:39/2/1102015-05-19HighWireOUPalcalc:39:2
CHANGES IN COMPOSITION AND PROPERTIES OF ERYTHROCYTE MEMBRANE IN CHRONIC ALCOHOLICS
Parmahamsa, M.
Reddy, K. Rameswara
Varadacharyulu, N.
ORIGINAL ARTICLES
<b>Aims and Methods:</b> Alterations in cholesterol and phospholipid contents as well as fluidity and lipid peroxidation in erythrocyte membranes from chronic alcoholic humans were investigated. <b>Results:</b> While an increase in cholesterol with no change in phospholipid content was observed in erythrocyte membranes, the phospholipid content increased with no change in cholesterol in plasma. <b>Conclusions:</b> An increase in microviscosity and a consequent decrease in membrane fluidity were evident from the studies of fluorescent hydrocarbon pyrene mobility in the bilayer of erythrocytes in chronic alcoholics. Also, an enhancement in the lipid peroxidation of erythrocytes from alcoholics is indicative of structural damage of membrane resulting from oxidative stress.
Oxford University Press
2004-03-01 00:00:00.0
TEXT
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http://alcalc.oxfordjournals.org/cgi/content/short/39/2/110
http://dx.doi.org/10.1093/alcalc/agh034
en
Copyright (C) 2004, Medical Council on Alcohol
oai:open-archive.highwire.org:alcalc:39/2/1132015-05-19HighWireOUPalcalc:39:2
MILDLY DISTURBED HEPATIC AND PANCREATIC FUNCTION DURING EARLY ABSTENTION FROM ALCOHOL IS ASSOCIATED WITH BRAIN ATROPHY AND WITH DISTURBED PSYCHOMETRIC PERFORMANCE
Junghanns, Klaus
Backhaus, Jutta
Veltrup, Clemens
Dageförde, Jürgen
Brückmann, Hartmut
Wetterling, Tilman
ORIGINAL ARTICLES
<b>Aims:</b> To investigate the relation of liver status and pancreatic function to disorders of the central nervous system during early abstention from alcohol. <b>Methods:</b> Sixty-seven alcohol-dependent patients (47 male) with a mean age of 42.3 ± 12.5 years, were assessed by clinical history, abdominal sonography, computerized tomography of the brain and with neuropsychological and serum enzyme tests. Patients with sonographically diagnosed cirrhosis were excluded. <b>Results:</b> Patients with fatty liver had more previous complicated detoxifications, but not more current signs of brain atrophy or impairment on neuropsychological tests. However, elevations in alpha amylase (AA), and gamma glutamyl transpeptidase (GGT) were associated with signs of cerebral atrophy. Higher serum GGT was related to impaired score on a number sequencing task (NST), and high AA with impairment on NST and on two tests of speed and perception. GGT and AA levels tended to be higher in older subjects. <b>Conclusions:</b> After detoxification from alcohol even mildly disturbed liver and pancreatic parameters, but not fatty liver itself, are associated with signs of brain atrophy and impaired psychometric performance. Age may be a confounding or contributing factor.
Oxford University Press
2004-03-01 00:00:00.0
TEXT
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http://alcalc.oxfordjournals.org/cgi/content/short/39/2/113
http://dx.doi.org/10.1093/alcalc/agh028
en
Copyright (C) 2004, Medical Council on Alcohol
oai:open-archive.highwire.org:alcalc:39/2/1192015-05-19HighWireOUPalcalc:39:2
NEUROPSYCHOLOGICAL STATUS OF ALCOHOL-DEPENDENT PATIENTS: INCREASED PERFORMANCE THROUGH GOAL-SETTING INSTRUCTIONS
Scheurich, A.
Müller, M. J.
Szegedi, A.
Anghelescu, I.
Klawe, C.
Lörch, B.
Kappis, B.
Bialonski, H.-G.
Haas, S.
Hautzinger, M.
ORIGINAL ARTICLES
<b>Aims:</b> The effects of goal-setting instructions on neuropsychological performance of alcohol-dependent patients and control subjects were assessed. <b>Methods:</b> 57 alcohol-dependent patients and 59 carefully age- and education-matched healthy control subjects underwent standard neuropsychological investigation. In addition, the goal-setting paradigm was used to systematically manipulate motivation. Participants were requested to calculate simple mathematical problems repeatedly within phases of a 2-min duration receiving normal or goal setting-instructions (to increase performance in the next phase by 20%). <b>Results:</b> The patients demonstrated deficits in standard neuropsychological tests. Patients under goal-setting instructions demonstrated significantly higher improvement (correct responses: <it>P</it> = 0.016) relative to patients with standard instructions. Control subjects with goal-setting instructions demonstrated tendencies for higher improvement relative to control subjects with normal instructions. However, the differences were not significant. Interaction of group (patients vs. control subjects) and instructions (goal setting vs. normal) remained insignificant (<it>P</it> = 0.489) indicating that the increase through goal setting for the patients was not significantly higher than that for the control subjects. <b>Conclusions:</b> Despite of neuropsychological deficits in reasoning and psychomotor functioning, alcohol-dependent patients early in recovery are responsive to goal setting and able to increase neuropsychological performance. Therefore, goal-setting strategies might possibly be used in cognitive rehabilitation and therapy of alcohol-dependent patients. As there was no significant interaction in increase between patients and control subjects, our results do not support the hypothesis that the neuropsychological deficits are affected by or even caused by motivational limitations of the alcohol-dependent patients.
Oxford University Press
2004-03-01 00:00:00.0
TEXT
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http://alcalc.oxfordjournals.org/cgi/content/short/39/2/119
http://dx.doi.org/10.1093/alcalc/agh026
en
Copyright (C) 2004, Medical Council on Alcohol
oai:open-archive.highwire.org:alcalc:39/2/1262015-05-19HighWireOUPalcalc:39:2
CHILDHOOD TRAUMA IN ALCOHOLICS
Mirsal, Hasan
Kalyoncu, Ayhan
Pektas, Özkan
Tan, Devran
Beyazyürek, Mansur
ORIGINAL ARTICLES
<b>Aims:</b> Many studies have been conducted to evaluate the relationship between childhood trauma and alcoholism. In this study 80 alcoholics were chosen according to their hospitalization order. The control group consisted of 60 subjects, with no history of alcohol use, matched with the patient group in age and sex. <b>Methods:</b> A sociodemographic and clinical data form, a questionnaire focusing on traumatic life experiences in childhood and The Childhood Trauma Questionnaire, Hamilton Depression Rating Scale, and Hamilton Anxiety Rating Scale were applied to both groups. <b>Results:</b> Significant differences were found between the two groups on traumatic life experiences in childhood. Results suggested that childhood trauma positively correlates with anxiety and affective symptoms among alcoholics. <b>Conclusions:</b> Further studies are needed concerning this issue.
Oxford University Press
2004-03-01 00:00:00.0
TEXT
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http://alcalc.oxfordjournals.org/cgi/content/short/39/2/126
http://dx.doi.org/10.1093/alcalc/agh025
en
Copyright (C) 2004, Medical Council on Alcohol
oai:open-archive.highwire.org:alcalc:39/2/1302015-05-19HighWireOUPalcalc:39:2
UNITED KINGDOM AND UNITED STATES HEALTHCARE PROVIDERS' RECOMMENDATIONS OF ABSTINENCE VERSUS CONTROLLED DRINKING
Cox, W. Miles
Rosenberg, Harold
Hodgins, C. Hazel A.
Macartney, John I.
Maurer, Ken A.
ORIGINAL ARTICLES
<b>Aim:</b> To assess whether selected characteristics of problem drinkers influence treatment goal recommendations — abstinence or controlled drinking — by healthcare providers in the UK and the US. <b>Methods:</b> Sixteen case-histories, composed with varying information regarding the clients' level of problem severity, degree of social support and sex, were read by 41 UK and 31 US healthcare providers, who then gave a recommendation of controlled drinking versus abstinence for each case on a seven-point Likert scale. <b>Results:</b> Overall, abstinence was recommended more strongly for higher-severity problem drinkers, those with higher social support (an unpredicted finding), and for female clients. Controlled drinking was more often recommended in the UK than in the US. However, the degree to which drinkers' problem severity, social support and sex each affected respondents' ratings depended on the level of one or more of the other variables and the country of the respondents. <b>Conclusion:</b> The degree to which healthcare providers recommend abstinence or controlled drinking as an outcome goal for problem drinkers varies according to both client characteristics and the country in which they work.
Oxford University Press
2004-03-01 00:00:00.0
TEXT
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http://alcalc.oxfordjournals.org/cgi/content/short/39/2/130
http://dx.doi.org/10.1093/alcalc/agh035
en
Copyright (C) 2004, Medical Council on Alcohol
oai:open-archive.highwire.org:alcalc:39/2/1352015-05-19HighWireOUPalcalc:39:2
TWO-YEAR OUTCOME OF COPING SKILLS TRAINING, GROUP SUPPORT AND INFORMATION FOR SPOUSES OF ALCOHOLICS: A RANDOMIZED CONTROLLED TRIAL
Hansson, Helena
Zetterlind, Ulla
Åberg-Örbeck, Kirsten
Berglund, Mats
ORIGINAL ARTICLES
<b>Aim:</b> To evaluate three different intervention programmes for spouses of alcoholics. <b>Methods:</b> 39 spouses of alcoholics (36 women and 3 men) with an average age of 47 years (ranging from 23 to 60 years) were randomly assigned to one of the three interventions: Coping Skills Training, Group Support, and Information. Follow-up interviews were conducted 12 and 24 months after completing the programme. Coping Behaviour Scale, Symptom Checklist 90 (SCL-90), Hardship Scale and AUDIT at admission and at follow-up were compared. 38 of the 39 spouses completed the 24-month follow-up examination. <b>Results:</b> Improvements of coping behaviour, psychiatric symptoms and hardship noted at the 12-month follow-up examination were still evident in all groups at the 24-month follow-up examination. The three groups scored similarly at 24 months on the four scales. <b>Conclusions:</b> A <it>post hoc</it> examination of subjects with SCL-90 scores above general population means, showed less improvement in the Information group than the two therapy groups combined (<it>P</it> < 0.05).
Oxford University Press
2004-03-01 00:00:00.0
TEXT
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http://alcalc.oxfordjournals.org/cgi/content/short/39/2/135
http://dx.doi.org/10.1093/alcalc/agh024
en
Copyright (C) 2004, Medical Council on Alcohol
oai:open-archive.highwire.org:alcalc:39/2/1412015-05-19HighWireOUPalcalc:39:2
WISHES AND EXPECTATIONS OF ALCOHOLIC PATIENTS CONCERNING THEIR THERAPY
Schneider, U.
Kroemer-Olbrisch, T.
Wedegärtner, F.
Cimander, K. F.
Wetterling, T.
ORIGINAL ARTICLES
<b>Aim:</b> To assess the wishes and expectations of alcoholic patients concerning their therapy. <b>Methods:</b> 227 alcohol-dependent patients from three sites in two cities in Germany completed a questionnaire about their aspirations for the outcome (20 items) and their expectations about the elements (23 items) of treatment. <b>Results:</b> Some components of treatment were equally important to men and women (a life without alcohol, individual sessions during therapy). Women attached more importance than men to ‘strengthening of self-esteem’ and ‘an environment of tranquillity and security’. Most patients in this study were aware of their alcohol dependence, which limits the generalizability of these results to patients at earlier stages of recovery. <b>Conclusion:</b> Patients request individual, patient-oriented treatment. Some differences in expectations between men and women suggest that a gendered approach in treatment could mean an increase in patients' satisfaction, and thus a decrease in drop-outs.
Oxford University Press
2004-03-01 00:00:00.0
TEXT
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http://alcalc.oxfordjournals.org/cgi/content/short/39/2/141
http://dx.doi.org/10.1093/alcalc/agh029
en
Copyright (C) 2004, Medical Council on Alcohol
oai:open-archive.highwire.org:alcalc:39/2/1462015-05-19HighWireOUPalcalc:39:2
ENCOURAGING GP ALCOHOL INTERVENTION: PILOT STUDY OF CHANGE-ORIENTATED REFLECTIVE LISTENING (CORL)
McCambridge, Jim
Platts, Simon
Whooley, David
Strang, John
ORIGINAL ARTICLES
<b>Aims:</b> To test the feasibility of delivery and potential value of a brief motivational enhancement intervention targeting GPs in relation to alcohol as a public health issue, and to compare data obtained with similar attempts to influence GP intervention with drug users. <b>Method:</b> 21 GPs who were not involved in the treatment of drug dependence received a telephone-administered ‘change-orientated reflective listening’ (CORL) intervention, based on Motivational Interviewing, with an informational adjunct. Assessments were made at baseline and at 2–3 months of activity and willingness to deliver specified alcohol-related interventions, plus overall therapeutic commitment and motivation. Qualitative data was obtained. <b>Results:</b> There was no change over time in the sample as a whole, with very modest evidence of benefit among individual practitioners. Comparisons with cannabis and drug misuse intervention targets suggest that it may be more difficult to alter views on intervening with drinkers. <b>Conclusions:</b> Further attempts are needed to influence practitioner motivation, based on improved understanding of GP views on the delivery of alcohol interventions.
Oxford University Press
2004-03-01 00:00:00.0
TEXT
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http://alcalc.oxfordjournals.org/cgi/content/short/39/2/146
http://dx.doi.org/10.1093/alcalc/agh027
en
Copyright (C) 2004, Medical Council on Alcohol
oai:open-archive.highwire.org:alcalc:39/2/1502015-05-19HighWireOUPalcalc:39:2
INCREASED CEREBELLAR PET GLUCOSE METABOLISM CORRESPONDS TO ATAXIA IN WERNICKE-KORSAKOFF SYNDROME
Fellgiebel, Andreas
Siessmeier, Thomas
Winterer, Georg
Lüddens, Hartmut
Mann, Klaus
Schmidt, Lutz G
Bartenstein, Peter
CASE REPORT
<b>Aims:</b> To investigate a possible relationship between cerebellar glucose metabolism and recovery from ataxia in the first months of acute Wernicke–Korsakoff syndrome. <b>Methods:</b> Two cases of alcoholic Wernicke–Korsakoff syndrome were followed up with the clinical status and cerebral glucose metabolism over a 4- and 9-month period. <b>Results:</b> Initially both patients showed severe ataxia and elevated cerebellar glucose metabolism that decreased corresponding to the restitution of stance and gait. <b>Conclusion:</b> Increased cerebellar glucose metabolism at the onset of the illness may reflect the reorganization process of disturbed motor skills and may indicate cerebellar plasticity.
Oxford University Press
2004-03-01 00:00:00.0
TEXT
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http://alcalc.oxfordjournals.org/cgi/content/short/39/2/150
http://dx.doi.org/10.1093/alcalc/agh016
en
Copyright (C) 2004, Medical Council on Alcohol
oai:open-archive.highwire.org:alcalc:39/2/752015-05-19HighWireOUPalcalc:39:2
ACCURACY OF CARBOHYDRATE-DEFICIENT TRANSFERRIN IN THE DETECTION OF EXCESSIVE ALCOHOL CONSUMPTION: A SYSTEMATIC REVIEW
Koch, Hèlen
Meerkerk, Gert-Jan
Zaat, Joost O. M.
Ham, Maria F.
Scholten, Rob J. P. M.
Assendelft, Willem J. J.
REVIEW
<b>Aims:</b> Excessive alcohol consumption is a common problem in society and medical practice. There is a need for a diagnostic tool with both high sensitivity and specificity for the detection of excessive alcohol consumption in unselected medical populations. Therefore, we evaluated the diagnostic accuracy of carbohydrate-deficient transferrin (CDT) in the detection of excessive alcohol consumption. <b>Methods:</b> Computerised literature searches in Medline, Embase and Current Contents databases (01/1966–06/2003) and reference checking. Articles on the detection of excessive alcohol consumption reporting CDT levels and self-reported alcohol consumption as a reference test were selected (<it>n</it> = 101). Studies concerning treatment, relapse detection and traffic offenders were excluded. Quality assessment and data-extraction was done by two reviewers independently. Only studies scoring positive on core validity criteria by Lijmer were eligible for quantitative analysis (<it>n</it> = 29). <b>Results:</b> Only two CDT-assays (CDTect and CDTriTIA) were evaluated in more than two high validity studies fulfilling the criteria for inclusion in the statistical analysis. Sensitivity of CDTect (14 data points) ranged from 20 to 85%, whereas specificity ranged from 77 to 95%. A summary ROC curve was computed for CDTect. Sensitivity of CDTTriTIA (4 data points) ranged from 10 to 67%, and specificity ranged from 90 to 100%. No summary measure could be computed for CDTTriTIA. The heterogeneity of results could not be explained clinically. <b>Conclusions:</b> The validity of CDT as a diagnostic tool is still questionable. If the higher values for sensitivity that some studies report can be confirmed by others it is a useful diagnostic tool in unselected populations. However, more methodologically sound, comparable studies need to be performed before firm conclusions can be drawn.
Oxford University Press
2004-03-01 00:00:00.0
TEXT
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http://alcalc.oxfordjournals.org/cgi/content/short/39/2/75
http://dx.doi.org/10.1093/alcalc/agh031
en
Copyright (C) 2004, Medical Council on Alcohol
oai:open-archive.highwire.org:alcalc:39/2/862015-05-19HighWireOUPalcalc:39:2
FAMILY INTERVENTIONS FOR ALCOHOL PROBLEMS
Hodgson, Ray
CONFERENCE REPORT
A growing body of evidence demonstrates that family interventions should be towards the top of the list of effective alcohol prevention and treatment approaches. A recent conference run by the UK Alcohol Education and Research Council presented some of this evidence (go to: <inter-ref locator="aerc.org.uk" locator-type="url">aerc.org.uk</inter-ref> then ‘News’ for a summary).
Oxford University Press
2004-03-01 00:00:00.0
TEXT
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http://alcalc.oxfordjournals.org/cgi/content/short/39/2/86
http://dx.doi.org/10.1093/alcalc/agh033
en
Copyright (C) 2004, Medical Council on Alcohol
oai:open-archive.highwire.org:alcalc:39/2/882015-05-19HighWireOUPalcalc:39:2
CHRONIC ETHANOL CONSUMPTION REGULATES CANNABINOID CB1 RECEPTOR GENE EXPRESSION IN SELECTED REGIONS OF RAT BRAIN
Ortiz, Sergio
Oliva, José M.
Pérez-Rial, Sandra
Palomo, Tomás
Manzanares, Jorge
ORIGINAL ARTICLES
<b>Aims:</b> The aim of this study was to examine the effects of chronic ethanol consumption in cannabinoid CB<inf>1</inf> receptor gene expression in Wistar rats. <b>Methods:</b> Rats were exposed to a bottle containing a solution of ethanol (10% v/v) and saccharin (0.25% w/v) for 52 days. At the end of this period, rats were killed by decapitation and cannabinoid CB<inf>1</inf> receptor gene expression was measured by <it>in situ</it> hybridization histochemistry. <b>Results:</b> Our results indicated that chronic ethanol consumption reduced cannabinoid CB<inf>1</inf> receptor gene expression in caudate-putamen (CPu) (24%), ventromedial nucleus of the hypothalamus (VMN) (43%), CA1 (27%) and CA2 (22%) fields of hippocampus and increased dentate gyrus (DG) (30%). <b>Conclusions:</b> These results reveal for the first time that prolonged exposure to ethanol produces marked alterations in cannabinoid CB<inf>1</inf> receptor gene expression in selected regions of the rat brain, supporting an interaction between ethanol consumption and the endogenous cannabinoid receptor. Furthermore, these findings suggest that cannabinoid CB<inf>1</inf> receptor may be considered as a new pharmacological target for treating ethanol dependence.
Oxford University Press
2004-03-01 00:00:00.0
TEXT
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http://alcalc.oxfordjournals.org/cgi/content/short/39/2/88
http://dx.doi.org/10.1093/alcalc/agh036
en
Copyright (C) 2004, Medical Council on Alcohol
oai:open-archive.highwire.org:alcalc:39/2/932015-05-19HighWireOUPalcalc:39:2
AMINO-ACID-DEPENDENT, DIFFERENTIAL EFFECTS OF ETHANOL ON GLUCOSE PRODUCTION IN RABBIT KIDNEY-CORTEX TUBULES
Derlacz, Rafal A.
Jagielski, Adam K.
Kiersztan, Anna
Winiarska, Katarzyna
Drozak, Jakub
Poplawski, Piotr
Wegrzynowicz, Michal
Chodnicka, Katarzyna
Bryla, Jadwiga
ORIGINAL ARTICLES
<b>Aims:</b> The effect of ethanol on glucose synthesis in kidney-cortex tubules of control and diabetic rabbits has been investigated. <b>Methods:</b> Both freshly isolated and grown in primary cultures, kidney-cortex tubules were incubated with alanine or aspartate plus lactate or glycerol plus octanoate in the absence and presence of 100 mmol/l ethanol. <b>Results:</b> In freshly isolated renal tubules incubated in the presence of alanine plus lactate or glycerol plus octanoate, and in tubules grown in primary culture in the medium containing alanine plus lactate plus octanoate alcohol, resulted in about 30% decrease in glucose formation. A diminished glucose production in freshly isolated tubules was accompanied by: (i) a decrease in alanine utilization, (ii) an increase in lactate or glycerol consumptions and (iii) a decline in GSH:GSSG ratio. The ethanol action was not abolished by 4-methylpyrazole, an inhibitor of alcohol dehydrogenase (ADH). In view of ethanol-induced changes in gluconeogenic intermediates it is likely that in the presence of alanine plus glycerol plus octanoate ethanol causes a decline in flux through phosphoenolpyruvate carboxykinase, probably due to either an increase in intracellular content of 2-oxoglutarate, inhibitor of this key gluconeogenic enzyme and/or an enhanced flux through pyruvate kinase, as concluded from an increased lactate formation in the presence of glycerol in the incubation medium. In renal tubules grown in primary cultures in the presence of alanine plus lactate plus octanoate a decrease in GSH:GSSG ratio was accompanied by elevated generation of reactive oxygen species (ROS). Upon replacement of alanine by aspartate ethanol affected neither glucose production, substrate uptake, ROS accumulation nor GSH:GSSG ratio. <b>Conclusions:</b> In the presence of alanine ethanol-induced decrease in glucose production and elevation of ROS might cause a limited NADPH generation resulting in a decrease in the intracellular GSH:GSSG ratio. On the contrary, aspartate might protect against ROS generation, so intensive gluconeogenesis supports NADPH generation and in consequence high values of the intracellular GSH:GSSG ratio are maintained.
Oxford University Press
2004-03-01 00:00:00.0
TEXT
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http://alcalc.oxfordjournals.org/cgi/content/short/39/2/93
http://dx.doi.org/10.1093/alcalc/agh038
en
Copyright (C) 2004, Medical Council on Alcohol