bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypothalamic‐Pituitary‐Thyroid Axis in Chronic Alcoholism. II. Deiodinase Activities and Thyroid Hormone Concentrations in Brain and Peripheral Tissues of Rats Chronically Exposed to Ethanol
Authors: Baumgartner Andreas , Heyne Andrea , Campos‐Barros Angel , Köhler Ralf , Müller Frank , Meinhold Harald , Rommelspacher Hans , Wolffgramm Jochen 
Published: April 2006

Thyroxine (T4), triiodothyronine (T3) concentrations, and the activities of the three deiodinase isoenzymes were measured in different brain regions and peripheral tissues of rats. According to an animal model of alcohol addiction, “behaviorally” dependent rats having lost control over their intake of ethanol were compared with alcohol‐naive controls and ethanol‐experienced, but “controlled” consumers. The two kinds of alcohol‐experienced rats were investigated either 24 hr or 3 months after ethanol withdrawal. The results of these four groups were compared with those of an ethanol‐naive control group.During withdrawal, the activities of type II 5′‐deiodinase (which catalyzes deiodination of T4, and T3 in the CNS) in both the “behaviorally dependent” rats and the “controlled drinkers” were significantly lower than in the alcohol‐naive controls in the frontal cortex, parieto‐occipital cortex, hippocampus, and striatum, but not in the cerebellum or pituitary. Probably as a result, the tissue concentrations of T4 were higher in areas of the CNS in the groups exposed to alcohol. However, the T3 concentrations were normal. No relevant differences were seen between the activities of type III 5‐deiodinase (which catalyzes the further deiodination of T3) observed in these groups. Atter 3 months of abstinence, the type II 5′‐deiodinase activities had almost returned to nomal in both “controlled drinkers” and “behaviorally dependent” animals, whereas type III 5‐deiodinase activity was inhibited, possibly to maintain physiological concentrations of T3 during abstinence. Indeed, the tissue levels of T3 were normal in the areas of the CNS, and the T4 levels were still elevated. However, the liver concentrations of T3 and T4 were significantly lower in the “behaviorally dependent” animals than in the “controlled” drinkers after 3 months of abstinence, whereas no differences were found between the T4 and T3 concentrations in the areas of the CNS investigated in the two groups exposed to ethanol.These results suggest that chronic administration of ethanol affects intracellular thyroid hormone metabolism in both rat CNS and liver in a highly complex manner. No direct evidence of ethanolinduced enhancement of tissue uptake or concentrations was obtained. However, taking into account the numerous similarities between the clinical picture of hyperthyroidism and the symptomatology of alcoholism, it may be hypothesized that ethanol may directly influence any step in the as yet unknown biochemical cascade of thyroid hormone function.
Role of Magnesium and Calcium in Alcohol‐Induced Hypertension and Strokes as Probed by In Vivo Television Microscopy, Digital Image Microscopy, Optical Spectroscopy, 31P‐NMR, Spectroscopy and a Unique Magnesium Ion‐Selective Electrode
Authors: Altura Burton M. , Altura Bella T. 
Published: April 2006

It is not known why alcohol ingestion poses a risk for development of hypertension, stroke and sudden death. Of all drugs, which result in body depletion of magnesium (Mg), alcohol is now known to be the most notorious cause of Mg‐wasting. Recent data obtained through the use of biophysical (and noninvasive) technology suggest that alcohol may induce hypertension, stroke, and sudden death via its effects on intracellular free Mg2+ ([Mg2+]), which in turn alter cellular and subcellular bioenergetics and promote calcium ion (Ca2+) overload. Evidence is reviewed that demonstrates that the dietary intake of Mg modulates the hypertensive actions of alcohol. Experiments with intact rats indicates that chronic ethanol ingestion results in both structural and hemodynamic alterations in the microcirculation, which, in themselves, could account for increased vascular resistance. Chronic ethanol increases the reactivity of intact microvessels to vasoconstrictors and results in decreased reactivity to vasodilators. Chronic ethanol ingestion clearly results in vascular smooth muscle cells that exhibit a progressive increase in exchangeable and cellular Ca2+ concomitant with a progressive reduction in Mg content. Use of 31P‐NMR spectroscopy coupled with opticalbackscatter reflectance spectroscopy revealed that acute ethanol administration to rats results in dose‐dependent deficits in phosphocreatine (PCr), the [PCr]/[ATP] ratio, intracellular pH (pHi), oxyhemoglobin, and the mitochondrial level of oxidized cytochrome oxidase aa3 concomitant with a rise in brain‐blood volume and inorganic phosphate. Temporal studies performed in vivo, on the intact brain, indicate that [Mg2+], is depleted before any of the bioenergetic changes. Pretreatment of animals with Mg2+ prevents ethanol from inducing stroke and prevents all of the adverse bioenergetic changes from taking place.Use of quantitative digital imaging microscopy, and mag‐fura‐2, on single‐cultured canine cerebral vascular smooth muscle, human endothelial, and rat astrocyte cells reveals that alcohol induces rapid concentration‐dependent depletion of [Mg2+], These cellular deficits in [Mg2+], seem to precipitate cellular and subcellular disturbances in cytoplasmic and mitochondrial bioenergetic pathways leading to Ca2+ overload and ischemia. A role for ethanol‐induced alterations in [Mg2+], should also be considered in the well‐known behavioral actions of alcohol.
Screening for Pregnancy Risk‐Drinking
Authors: Russell Marcia , Martier Susan S. , Sokol Robert J. , Mudar Pamela , Bottoms Sidney , Jacobson Sandra , Jacobson Joseph 
Published: April 2006

The efficacy of alcohol screening questionnaires, the TWEAK, TACE, NET, MAST, and CAGE, in detecting periconceptional riskdrinking, 1 oz absolute alcohol/day, was investigated in 4743 African‐American women attending an inner‐city prenatal clinic who had reported ever drinking. Sensitivity, specificity, positive predictive value, efficiency, follow‐up rates, and receiver operating characteristics of the questionnaires were examined to compare the overall effectiveness of the questionnaires and their performance at cutpoints defining positive scores ranging from 1 to 3. Relatively little difference between TWEAK, T‐ACE, and MAST was seen in the receiver operating characteristic accuracy indices; NET and CAGE lagged behind. Sensitivity/specificity scores for the two questionnaires most sensitive at cut‐point 1 were TWEAK (87/72) and T‐ACE (83/75). At cut‐point 2, sensitivity was optimized with respect to specificity; TWEAK (79/83) was significantly more sensitive than T‐ACE (70/85; p = 0.002). At cut‐point 3, the two most sensitive tests were MAST (61/92) and TWEAK (59/94). In general, measures of merit were not greatly affected by the time between conception and the administration of the screens. Screening was most sensitive for women interviewed during the first 15 weeks of pregnancy; riskdrinkers tended to delay entry into prenatal care, increasing positive predictive values associated with screening later in pregnancy.This study confirms the utility, when screening for risk‐drinking during pregnancy, of brief questionnaires that assess alcohol intake indirectly by asking women about their tolerance to alcohol's effects, psychological consequences of drinking, and significant others' concern about their drinking. It validates T‐ACE and provides preliminary data indicating that TWEAK may outperform T‐ACE.
Influence of Ethanol Intake on Mammary Gland Morphology and Cell Proliferation in Normal and Carcinogen‐Treated Rats
Authors: Singletary Keith W. , McNary Minnie Q. 
Published: April 2006

Alcohol consumption has been reported to increase breast cancer risk in a majority of epidemiological studies and to enhance, at specific dietary concentrations, both the initiation and promotion stages of chemically induced rat mammary tumorigenesis. However, there is limited information regarding possible mechanisms for this effect.The present studies were conducted to examine a possible mechanism for the promoting effect of ethanol on chemically induced mammary tumorigenesis. The influence of chronic ethanol intake by female rats on the progress of differentiation and on the rate of target structure cell proliferation of the mammary gland was evaluated. Results of these studies indicate that ethanol intake at 20% and 30% of calories by female rats between the ages of 55 and 94 days (a period associated with the promotion stage of experimental mammary tumorigenesis) results in a delay in the differentiation of the mammary gland. This delay in gland maturation observed for rats consuming ethanol was evidenced by an increase in the quantity of less mature terminal‐end bud (TEB) structures and a decrease in the quantity of more mature alveoler bud structures. The DNA labeling index of the target structure TEB increased significantly for rats consuming ethanol. These changes in mammary gland maturation and in TEB DNA labeling index were observed for both normal and carcinogen‐treated rats consuming ethanol. Also, serum progester‐one, but not estradiol, was significantly decreased for animals consuming ethanol at 30% of calories compared with isocaloric controls. The correlation of these changes in the mammary gland with the reported enhancement by ethanol of the promotion stage of experimental rat mammary tumorigenesis is discussed.
Reduced Serotonergic Immunoreactive Fibers in the Forebrain of Alcohol‐Preferring Rats
Authors: Zhou Feng C. , Bledsoe Sharon , Lumeng Larry , Li Ting‐Kai 
Published: April 2006

Our previous study indicated that 5‐hydroxytryptamine (5‐HT) immunoreactive fiber densities were decreased in specific areas of the brain in alcohol‐preferring rats (P) when compared with alcohol‐nonpreferring rats (NP). The results of our current study show that there are quantitative and qualitative differences in 5‐HT innervation in other selected regions of the forebrains of P rats. The 5‐HT fiber density in the brains of young adult P and NP rats was measured by immunocytochemistry and quantitative image analysis. A routine error of two‐dimensional quantitation of nerve fiber was addressed and an adjustment was made. The amount of 5‐HT fibers was significantly lower in CA4 and fasciola cinereum of the dorsal hippocampus, caudate‐putamen, and hypothalamus of the P as compared with NP rats (unpaired Student's t tests).In examining the fiber types, we found that, in the frontal cortical and hippocampal regions, where normally fine 5‐HT fibers with small varicosities and thick 5‐HT fibers with large varicosities coexist, fewer fine 5‐HT fibers were seen in P rats as compared with NP rats the fine fibers are known to be vulnerable to abusive drugs. These observations indicate that (a) there are quantitative differences in 5‐HT innervation or that the 5‐HT in some 5‐HT fibers is reduced to a level undetectable by immunocytochemistry, and (b) the fine 5‐HT fibers are specifically reduced to a greater degree in the selected brain regions of P rats when compared with that of NP rats. The involvement of the 5‐HT system in the alcohol abuse is discussed.
Detection of Alcoholism in Three Populations by the Brief‐Mast
Authors: Chan Arthur W. K. , Pristach Edward A. , Welte John W. 
Published: April 2006

The brief MAST (B‐MAST) questionnaire was used to detect alcoholism in three populations, namely, alcoholics in treatment, clinical outpatients, and the general population. Nearly all the alcoholics in treatment tested positive in the 8‐MAST (99.2%), for lifetime as well as for current (past year) alcohol‐related problems. Among the clinical outpatients and general population, 35.6% and 20.2% respectively, tested positive for lifetime alcohol problems, but only 19.6% and 7.6%, respectively, tested positive for past‐year alcohol problems.The sensitivity/specificity of the B‐MAST (lifetime) was 64.7%/ 90.0% and 48.30//96.4% in the clinical outpatients and general population, respectively. Even lower sensitivity (28.2%) was obtained when the B‐MAST was used to detect past‐year alcohol problems in the general population sample. The poor sensitivity of the B‐MAST in the general population was probably because most of the B‐MAST questions deal with severe alcohol problems, and they are not sufficiently sensitive to detect those who drank heavily but who had not yet developed these alcohol problems. Anomalous responses to the two questions about “normal drinker” and to the question about “attendance in AA meeting” also contributed (<3%) to inflated positive B‐MAST scores. There were gender differences, and to a lesser extent, racial differences (Whites versus Blacks), in the responses to individual 8‐MAST questions in the three subject populations, with more males than females in each group reporting more alcohol‐related problems. However, there were no gender and racial differences in the average B‐MAST scores among those clinical outpatients and general population subjects who tested positive.
Comparison of Direct Interview and Family History Diagnoses of Alcohol Dependence
Authors: Rice John P. , Reich Theodore , Bucholz Kathleen K. , Neuman Rosalind J. , Fishman Roberta , Rochberg Nanette , Hesselbrock Victor M. , Nurnberger John I. , Schuckit Marc A. , Begleiter Henri 
Published: April 2006

Using data from The Collaborative Study on the Genetics of Alcoholism, we compare direct interview diagnoses of alcohol dependence to those obtained by history from family members. Using a requirement of three or more positive implications by history, the specificity, sensitivity, and positive predictive values are 98%, 39%, and 45%, respectively.A logistic analysis found the gender of the relative and alcoholism in the informant to be significant, but not the gender of the informant. The partial odds ratio of a diagnosis at interview associated with a positive family history diagnosis was 13.6. The relationship between the informant and relative was significant, with negative reports from an offspring or mate more influential than a negative report from a parent or second‐degree relative.We derived a recursive equation to combine a variable number of family history reports, wherein the probabilities associated with a single report are computed from the logistic analysis. This permits the use of family history information both as a proxy for an uninterviewed relative, as well as a second source of information to be used in the analysis of genetic family data.
Correlates of Alcohol‐Related Problems in African‐American and White Gynecologic Patients
Authors: Lozina Cherelle , Russell Marcia , Mudar Pamela 
Published: April 2006

The purpose of this study was to assess racial differences in the risk of alcohol‐related problems associated with alcohol consumption, regular psychoactive drug use, a family history of alcohol‐related problems, sociodemographic factors (age and education), and social roles (work, marital, and parental) among nonabstaining African‐American and White gynecologic outpatients. In addition, work, marital, and parental roles were investigated to determine whether they mediated or explained racial differences observed in relationships between these factors and alcohol‐related problems. Respondents were 630 African‐American women and 769 White women aged 13–77 who were systematically sampled from three obstetric/gynecologic clinics and two private practices in Erie County, New York. Hierarchical multiple regression analysis was used to test the significance of main effects of these factors on alcohol‐related problems, to test the interactive effects of race with each factor, and to test the interactive effects of social roles with alcohol consumption, the only factor for which a racial difference was observed in its relationship with alcohol‐related problems.Overall, results indicated that correlates of alcohol‐related problems were similar for African‐American and White women. Higher risk of alcohol‐related problems was associated with lower levels of education and lack of work and parental roles. In addition, married women who drank heavily were at higher risk of alcohol‐related problems than unmarried women who drank heavily. The fact that White women were more likely than African‐American women to be married contributed to the observation that the relationship between alcohol consumption and alcohol‐related problems was stronger among White women than among African‐American women.
Vasodilatory State of Decompensated Cirrhosis: Relation to Hepatic Dysfunction, Ascites, and Vasoactive Substances
Authors: Friedman Howard S. , Cirillo Nicholas , Schiano Frank , Nathan Paul , Khan Sultan , Rosero Hugo , Vaseghi Mehdi , Sacchi Terrence , Vasavada Balendu , Bjornson Loring 
Published: April 2006

The objective of this study was to determine the relations between the hallmark circulatory finding of decompensated cirrhosis, a reduced systemic vascular resistance (SVR), and the indices of hepatic decompensation, the accumulation of ascites, and the concentrations of various vasoactive substances.At a university‐affiliated teaching hospital, eighteen hospitalized patients with cirrhosis and 18 age‐ and sex‐matched healthy subjects were used. This was a case‐control study.Measurements included cardiac dimensions and indices derived from echocardiograms and Doppler studies, abdominal ultrasound estimates of ascites, indices of hepatic function, and various serum (S) and urinary (U) substances.Results showed that cirrhotics had increased left atrial and left ventricular dimensions, left ventricular mass, heart rate, cardiac output (CO), transvalvular velocities, and a decreased SVR. SVR was related to hepatic dysfunction, as reflected by an abnormal prothrombin time ratio (r= ‐0.64, p= 0.006), and also related to overall severity of liver disease as estimated by the Child‐Pugh score (r= ‐0.53, p = 0.044). Although cirrhotics with ascites generally had a reduced SVR, estimates of ascites were directly related to SVR (r = 0.57, p = 0.03) and inversely related to CO (r= ‐0.53, p= 0.04). Concentrations of S and U digoxin‐like immunoreactive substance (DLIS) were also increased, but the concentrations of S glucagon and estradiol were not elevated. The accumulations of S and U DLIS, S glucagon, and S estradiol were all related to hepatic dysfunction. S estradiol was also related to SVR (r = ‐0.55, p= 0.04), but this was only evident with S estradiol expressed as a logarithm and did not emerge as significant on a multivariate analysis.The reduced SVR observed in decompensated cirrhosis is related to various indices of hepatic dysfunction. Certain substances that accumulate in cirrhosis (such as DLIS, glucagon, and estradiol) do not explain the vasodilatation observed. Although ascites in decompensated cirrhosis generally signifies a vasodilated state, a reduced SVR may be found even before ascites is clinically evident, and tense ascites may actually obscure this finding.
Modulation of T‐Cell Adhesion Markers, and the CD45R and CD57 Antigens in Human Alcoholics
Authors: Cook Robert T. , Ballas Zuhair K. , Waldschmidt Thomas J. , Vandersteen Daniel , LaBrecque Douglas R. , Cook Brian L 
Published: April 2006

Direct and indirect evidence indicates that T cells are altered in alcoholics. The most commonly reported changes under direct examination have been consistent with an increased level of activation as reflected by shifts in the ratio of common leukocyte antigen isoforms expressed at the cell surface, by increases in the expression of class II antigen, or by alterations in the expression of various adhesion molecules. Functional evidence for T‐cell abnormality includes loss of delayed hypersensitivity and a number of findings attributed to dysregulation of B cells by alcoholic T cells; these include the widely reported disturbances of immunoglobulin production in vivo and a range of abnormal responses when T and B cells are combined in vitro.Detailed flow cytometric examination of T cells from alcoholics with or without active liver disease reveals a significant loss of l‐selectin CD8+ T cells, but not usually of CD4+ T cells. There is an inverse increase in the expression of CD11b on the CD8+ cells that have decreased L‐selectin+ percentages. Both CD8+ and CD4+ T cells in alcoholics display a significant loss of the CD45RA isoform and a gain of cells exhibiting the CD45RO isoform. Other surface alterations include increased expression of CD57, a marker most commonly associated on T cells with conditions of chronic increased antigenic exposure.It is argued that these and other T‐cell alterations in alcoholics are cytokine‐driven in part and result in T‐cell differentiation states that are functionally inappropriate. The results of these alterations may include reductions in normal lymphocyte traffic, an increase in cell‐mediated cytotoxicity, and intermittent loss of normal suppressor functions for immunoglobulin production permitting increased autoantibody formation. Chronic excessive antigen exposure may contribute at other times to the development of abnormal regulatory suppression of the immune response.
Ethanol Suppresses Growth Hormone‐Mediated Cellular Responses in Liver Slices
Authors: Xu Xiaowei , Ingram Rhonda L. , Sonntag William E. 
Published: April 2006

Previous studies indicate that both acute and chronic ethanol administration inhibit protein synthesis and decrease the secretion of insulin‐like growth factor‐1 (IGF‐1). Although IGF‐1 synthesis and secretion are regulated by growth hormone secretion from the pituitary gland, we assessed whether ethanol inhibits tissue response to growth hormone. Liver slices from male Sprague‐Dawley rats were prepared, placed into F‐12 media, and incubated at 37°C with [3H]leucine, and either 0.25 or 1 nM rat growth hormone and 0, 37 (physiological levels), or 175 mM (toxic levels) ethanol. Tissues were removed at 0,15,30, and 60 min. Protein synthesis increased linearly during this time period, and administration of growth hormone (1 nM) significantly increased protein synthetic rate by 48% (p < 0.01), whereas addition of 37 or 175 mM ethanol attenuated the effects of growth hormone (p < 0.01). Analysis of IGF‐1 mRNA indicated a 2‐fold increase in response to growth hormone (p < 0.01), whereas ethanol administration decreased the growth hormone‐induced rise of IGF‐1 mRNA. Ethanol (175 mM) inhibited the release of IGF‐1 into the media (p < 0.05). Ethanol did not alter growth hormone receptor binding, and exposure of tissue slices to ethanol did not influence the number of growth hormone receptors or the affinity of growth hormone for its receptor.Our results demonstrate that (1) growth hormone is a potent acute regulator of IGF‐1 mRNA and IGF‐1 peptide release, (2) ethanol inhibits growth hormone‐induced protein synthesis and induction of IGF‐1 gene expression, and (3) the inhibitory effects of ethanol on growth hormone occur without changing growth hormone receptor number or binding characteristics. We conclude that ethanol suppresses growth hormone‐induced signal transduction, resulting in a decrease in IGF‐1 gene expression.