bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alcohol‐Induced Inhibition of LH Secretion in Intact and Gonadectomized Male and Female Rats: Possible Mechanisms
Authors: Rivier Catherine , Rivest Serge , Vale Wylie 
Published: April 2006

Alcohol (EtOH) is reported to decrease gonadotropin secretion, but the mechanisms mediating these changes are not fully understood. The present study examined the ability of acutely or chronically administered EtOH to alter plasma luteinizing hormone (LH) and follicle stimulating hormone (FSH) levels in both male and female rats, and correlated these changes with blood EtOH levels (BALs); investigated possible changes in the pituitary responsiveness of animals exposed to EtOH; and probed the role of the paraventricular nucleus (PVN) of the hypothalamus in mediating alcohol‐induced decreases in plasma LH levels.The injection of 0.5 g EtOH/kg was accompanied by significantly higher BALs in females compared with males. This dose of alcohol did not alter rectal temperature, and only significantly (p≤ 0.01) decreased plasma LH levels in female rats. These findings were not altered by removal of gonadal steroids. Administration of 2.0 g EtOH/kg was followed by BALs that were comparable in both groups of rats at the 1‐ and 2‐hr time‐points, but were significantly (p≤ 0.01) higher in females 3 hr after treatment. Rectal T measurably decreased in all rats injected with 2 g EtOH/kg, though intact females showed the greatest change. This alcohol treatment also significantly (p≤ 0.01) inhibited immunoreactive LH release in both sexes, but there were no measurable changes in FSH values at any time. Using alcohol regimens which significantly lowered LH values in both sexes, we then showed that neither acute nor prolonged (7 days) treatment of male or female rats with alcohol measurably altered the LH response to 10, 30, or 100 ng gonadotropin‐releasing hormone (GnRH). Finally, we observed that in male rats, destruction of the PVN did not prevent the inhibitory effect of acute alcohol administration on LH secretion.These results indicate that alcohol‐induced decreases in plasma LH levels are not primarily mediated by changes in pituitary responsiveness to GnRH, and that the PVN is not necessary for the inhibitory effect of alcohol on LH secretion. It is therefore probable that alcohol acts outside the PVN to alter brain neurotransmitters that impact on GnRH‐secreting neurons.
Outcome in Subjects with Alcohol‐Provoked Seizures
Authors: Pieninkeroinen Ilkka P. , Telakivi Tiina M. , Hillborn Matti E. 
Published: April 2006

The outcome in 165 subjects with either an unknown (n= 93) or an alcohol‐related (n= 72) seizure etiology, admitted to the emergency room of a general hospital in 1977–1978, was assessed after 10 years on the basis of subsequent hospital records and death‐certificate‐based mortality data. Alcohol and/or drug poisoning was the most frequent cause of death in the group with alcohol‐related seizures. Sixty‐four percent of the deaths in this group were directly related to alcohol abuse. The crude mortality was 45.8 (expected 8.6)/100 persons/10 years in the group with alcohol‐related seizures and 15.1 (expected 6.0)/100 persons/10 years in the other group, the odds ratio between the groups being 4.8. Twenty percent of those with an unknown seizure etiology were found to show alcohol related seizures, while the seizure etiology remained unknown in 59%, and a specific etiology other than alcohol abuse was revealed in 21% during the follow‐up period.We conclude that alcohol abuse is an important, though often undetected, seizure etiology carrying a poor prognosis. The difference in mortality between the groups was due more to alcoholism than to seizures. There was no difference in mortality between those with a first alcohol‐related seizure and those with previous alcohol‐related seizures.
Treatment of Pregnant Alcohol‐Consuming Rats with Buspirone: Effects on Serotonin and 5‐Hydroxyindoleacetic Acid Content in Offspring
Authors: Tajuddin Nuzhath F. , Druse Mary J. 
Published: April 2006

This laboratory previously demonstrated that in utero ethanol exposure markedly impairs the development of the serotonergic system in rat brain. Developmental abnormalities could be detected as early as G15 in the brainstem and G19 in the cortex. Because of the importance of fetal serotonin (5‐HT) and 5‐HT1A receptors for the normal development of 5‐HT containing neurons, we initiated studies to determine whether administration of a 5‐HT1A agonist, buspirone, to pregnant rats could overcome the adverse effects of in utero ethanol exposure on the developing serotonergic system in offspring.Female, Sprague‐Dawley rats were given daily subcutaneous injections of buspirone (4.5 mg/kg) from gestational day 13 (G13) to G20. 5‐HT and 5‐hydroxyindoleacetic acid (5‐HIAA) content were determined in the cortex and cortical regions. These experiments demonstrated that the ethanol‐associated abnormalities in the development of the serotonergic system can be partially overcome by in utero exposure to buspirone. Specifically, whereas untreated ethanol rats had a deficiency of 5‐HT and/or 5‐HIAA in whole cortex on PN5, and in the motor cortex on PN19 and 35, no significant differences were detected in these regions of the age‐matched offspring of buspirone‐treated, ethanol‐fed rats. In contrast, the 5‐HT and 5‐HIAA deficiency in the somatosensory cortex of 19‐dayold offspring of ethanol‐fed rats was not corrected by in utero buspirone treatment.These results suggest that the abnormal development of cortical projections of serotonergic neurons may be due in part to the low fetal 5‐HT content in ethanol‐exposed rats and may potentially be overcome by in utero treatment with a 5‐HT1A agonist. However, additional studies are needed to elucidate the importance of dose and timing of buspirone administration, and the effects of in utero buspirone exposure on other components of serotonergic and nonserotonergic neurons.
Does Psychomotor Sensitivity to Alcohol Predict Subsequent Alcohol Use?
Authors: Rodriguez Lawrence A. , Wilson James R. , Nagoshi Craig T. 
Published: April 2006

Data from 42 male and 58 female subjects who participated in the Colorado Alcohol Research on Twins and Adoptees (CARTA) project were subjected to model‐fitting analyses. The aim of the present study was to use linear structural equation models to determine whether differences in previously measured psychomotor sensitivity to alcohol predict differences in self‐reported alcohol consumption over a 4‐year period. LISREL model‐fitting results indicate that, for male subjects, only rail walking insensitivity is predictive of alcohol use reported 2 years after their initial CARTA testing. For females, only hand steadiness sensitivity is predictive of alcohol use reported 2 years after their initial CARTA testing. The results for males support a hypothesis that would consider alcohol insensitive individuals at greater risk for alcohol abuse. The female results, however, would argue against such a hypothesis.With only one measure of sensitivity predicting alcohol use at only one out of four time points, in both men and women, the overall results suggest that our three measures of psychomotor sensitivity to alcohol are, in general, poor predictors of alcohol consumption in this sample.
Ethanol‐Induced Changes in Peripheral Blood and Splenic Natural Killer Cells
Authors: Blank Sally E. , Pfister Linda J. , Gallucci Randle M. , Meadows Gary G. 
Published: April 2006

Previous work demonstrated that splenic natural killer (NK) cell cytolytic activity was suppressed in ethanol‐consuming mice within 1 week and for as long as 10 weeks concurrent with ethanol intake. However, it is unknown if suppression of NK cell activity with ethanol consumption results from regional losses in NK cells. The present experiments were designed to examine the effect of ethanol on the percentage and total number of NK cells in the spleen and blood. Data indicate that, after 4 weeks of ethanol intake, NK cell activity of peripheral blood lymphocytes was also suppressed (50% of controls). With short‐term (2‐week) exposure, the percentage of NK cells in the blood and the spleen remained relatively constant. In the spleen, changes in the number of NK cells reflected generalized fluctuations in lymphocyte numbers rather than variation in the percentage of NK cells. NK cells were most sensitive to the effects of ethanol during long‐term (8‐week) ethanol intake, as demonstrated by significant reductions in the total percentage of NK 1.1+ cells in the blood, and the LGL‐1+ subset in the blood and spleen.These results provide insight into the mechanism of NK modulation by ethanol. Because NK cells were not selectively depleted after 2–4 weeks of ethanol intake, loss of cytolytically active NK cells cannot explain the suppression of in vitro cytolytic activity of cells from ethanol‐consuming mice. However, with prolonged ethanol intake (8 weeks), the depletion of NK cells, specifically the LGL‐1+ subset, may contribute to the overall suppression of NK cell cytolytic function.
Impact of Chronic Alcoholism on the Aging Rat: Changes in Nutrition, Liver Composition, and Mortality
Authors: Mendenhall C. L. , Rouster S. D. , Roselle G. A. , Grossman C. J. , Ghosn S. , Gartside P. 
Published: April 2006

The adverse effects of chronic alcohol consumption (mean 6.68 g/kg/d) were assessed in 150 male Sprague‐Dawley rats over their life span (25 months). Evaluations were performed at 2, 3, 8, 13, 19, and 25 months of age for changes in nutrition status, biochemical tests for liver injury, compositional changes in liver, and hepatic regenerative capacity. In spite of nearly identical caloric intake, alcohol treatment was associated with nutritional levels 10‐30% lower than controls.Maximal changes were observed at the two extremes of ages (2‐3 months and 19‐25 months). Hence, a nutritional contribution to other adverse changes could not be excluded. Fatty compositional increases (triglycerides) occurred early (5‐fold increases after 1 month of treatment) then declined to levels only slightly above controls. Biochemical tests on sera for liver injury (AST and total bilirubin) were consistently higher with alcohol treatment. Regenerative capacity measured by [3H]thymidine uptake after partial hepatectomy was initially elevated in the alcoholic then rapidly declined beyond 7 months of age. In control animals, an age‐related decline was also observed but occurred later beyond 12 months of age. Consistent with these adverse effects, ethanol diet survival was poorer than the pair‐fed control groups by 15% (median survival for alcoholics, 17 months vs. 20 months in controls).
Carbohydrate‐Deficient Transferrin as a Measure of Immoderate Drinking: Remaining Issues
Authors: Allen John P. , Litten Raye Z. , Anton Raymond F. , Cross Gerald M. 
Published: April 2006

A growing body of investigations demonstrate that elevated levels of carbohydrate‐deficient transferrin (CDT) effectively distinguishes alcoholics recently consuming large amounts of alcohol from light social drinkers or teetotalers. Nevertheless, important questions still remain concerning the value of CDT as a more generalized marker of alcohol consumption. Most important, the nature of the drinking pattern, including quantity and frequency, necessary to raise levels of CDT significantly remains unclear. Neither has research convincingly demonstrated that CDT is as accurate a marker for women, young adults, or non‐Caucasian ethnic groups as for White, middleaged men.Whereas CDT might serve as a useful outcome measure in trials of alcoholism treatment effectiveness, current research suggests that CDT is of limited value in identifying problematic drinking in general medical or community settings in which a broad continuum of drinkers is represented. Combining CDT with other biochemical or self‐report screening measures may, however, improve sensitivity in these contexts.At present, the most accurate laboratory technique to detect CDT seems to be isoelectric focusing. Additional research, however, is needed to resolve the issue of whether CDT is best quantitated as a simple value or if its ratio to total transferrin or non‐CDT results in higher predictive validity.
Biases in the Diagnosis of Alcoholism by the Family History Method
Authors: Roy Marc‐André , Walsh Dermot , Prescott Carol A. , Kendler Kenneth S. 
Published: April 2006

The authors explored the factors influencing the agreement of diagnoses of alcoholism obtained by a best‐estimate (BE) procedure versus those obtained by family history (FH) only, based on data from the Roscommon Family Study. The participants were first‐degree relatives of either schizophrenic subjects, subjects with affective disorders, or matched community controls. The FH information was obtained from first‐degree relatives of the participants, whereas the BE diagnoses included personal interview and medical records as well as FH information. Two types of error were distinguished: false‐negative FHs, who were diagnosed with alcoholism by BE but not by FH; and false‐positive FHs, who were diagnosed with alcoholism by FH but not by BE.The risk of false‐negative FHs was increased by young age of the subject and male gender of the informant, and decreased by a history of previous hospitalization of the subject. Conversely, the risk for false‐positive FHs was increased by older age of the subject, male gender of the subject, female gender of the informant, and informant's diagnosis of alcoholism. Comorbid diagnosis of nonaffective psychosis increased the risk of both types of error. It is concluded that when validated against a BE diagnosis, the FH diagnosis of alcoholism is subject to several biases and that the FH method is not a satisfactory substitute for BE diagnoses.
Helicobacter Pylori, Active Chronic Antral Gastritis, and Gastrointestinal Symptoms in Alcoholics
Authors: Hauge T. , Persson J. , Kjerstadius T. 
Published: April 2006

The frequency of Helicobacter pylori (Hp.) infection and active chronic antral gastritis among people with excessive alcohol consumption is not known. A high alcohol intake regularly causes acute gastroduodenitis. In this study, the prevalence of Hp. Infection and active chronic antral gastritis in alcoholics compared with nonalcoholic controls was studied. Further, the frequency of gastrointestinal symptoms was registered. Diagnostic methods for Hp. were compared.Twenty‐four alcoholics admitted to the hospital for detoxification underwent upper gastrointestinal endoscopy regardless of symptoms. Twelve individuals admitted to upper endoscopy mainly for dyspepsia, with low alcohol consumption and without gross pathology by upper endoscopy, were chosen as controls. Three diagnostic methods for Hp. were used: culture, direct microscopy, and histology.Hp. infection was found in 7 of the 24 alcoholics (29%) according to culture. In controls, 4 of 12 (33%) had a positive Hp. culture. In the alcoholic group, culture was more sensitive than histology. There was a good correlation between the different diagnostic methods in the control group. Histologically active chronic antral gastritis was found in 6 of the alcoholics (25%) and in 5 of the controls (42%). Five of the 7 Hp.‐positive alcoholics and all of the Hp.‐positive controls had an active chronic antral gastritis.Hp. infection is not more frequent in alcoholics than in controls. In both groups, there was a good correlation between Hp. infection and histologically, active chronic antral gastritis.
Prenatal Alcohol Exposure Alters the Hypothalamic‐Pituitary‐Adrenal Axis Response of Immature Offspring to Interleukin‐1: Is Nitric Oxide Involved?
Authors: Lee Soon , Rivier Catherine 
Published: April 2006

We have previously shown that following prenatal alcohol exposure, immature offspring showed blunted ACTH released in response to the peripheral administration of interleukin‐1β (IL‐1β). The present studies were conducted to investigate the role of changes in corticosteroid feedback (measured by altered adrenal responses to ACTH), corticotropin‐releasing factor (CRF) content of the median eminence (ME), and the influence of endogenous nitric oxide (NO). The injection of several doses of ACTH failed to indicate measurable differences between the corticosterone responses of offspring born to dams fed ad libitum [control (C)], pair‐fed (PF), or fed alcohol [ethanol (EtOH) = E]. CRF content in the ME, taken as an index of the amount of releasable peptide, showed a small, but statistically significant, decrease following prenatal alcohol exposure. A comparable change, however, was also noted in PF rats. As expected, the subcutaneous injection of IL‐1β (0.5 μg/kg) induced smaller increases in plasma ACTH levels of E than C pups. The response of PF animals was intermediate between that of E and C rats. Finally, we observed that inhibition of NO formation by the administration of the arginine derivative Lwnitro‐L‐arginine‐methylester significantly augmented ACTH secretion in all three experimental groups, and reversed the decreased corticotrophs' response to IL‐1β caused by prenatal alcohol.Taken together, our results suggest that the ability of prenatal alcohol exposure to alter ACTH released by immature pups in response to blood‐borne IL‐1β is probably not mediated through changes in adrenal responsiveness. We propose, on the other hand, that endogenous NO levels may be increased by the prenatal treatment, thereby interfering with the release of peptides from nerve terminals in the ME.
Maternal Ethanol Consumption: Effects on G Proteins and Second Messengers in Brain Regions of Offspring
Authors: Druse Mary J. , Tajuddin Nuzhath F. , Eshed Maya , Gillespie Roberta 
Published: April 2006

Previous work in this and other laboratories has demonstrated that in utero ethanol exposure adversely affects the development of the serotonergic, dopaminergic, cholinergic, and other neurotransmitter systems. In several of these systems, receptor number is significantly altered. To determine whether the altered number of two G protein‐linked receptors is reflected in changes in cell function, we examined dopamine‐stimulated adenylate cyclase in the striatum and cortex and carbachol‐stimulated phosphoinositide (PI) hydrolysis in the cortex. Serotonin‐stimulated cortical PI hydrolysis was assessed for comparison. We also studied G proteins that link adenylate cyclase and other second messenger systems to their receptors. The G proteins that were analyzed include the α‐subunits for Ga, Go, G11, G12, and G13. G proteins were analyzed in the cortex and cortical regions, as well as in the brain stem.The results of these experiments demonstrated that dopaminestimulated adenylate cyclase activity was comparable in the striatum of 5‐ and 19‐day offspring of control and ethanol‐fed rats and in the motor cortex of 19‐day offspring. We also found that carbachol‐ and serotonin‐stimulated hydrolysis of cortical phosphoinositides was unchanged in ethanol‐exposed offspring on gestational day 19, and on postnatal days 5 and 19. G protein content was examined by Western blot analysis, using antibodies directed against the α‐subunits of Ga, Go, and the G11/G12 and G13/Go combinations. These investigations indicated that, with two minor exceptions (∼10% change in the proteins detected by antibodies against the α‐subunits of the G11/G12 and G13/Go combinations), there were no significant differences in the content of any of the G proteins analyzed.
Expression of Tumor Necrosis Factor‐α and Interleukin‐6 Cell‐Surface Receptors of the Alveolar Macrophage in Alcohol‐Treated Rats
Authors: D'Souza Nympha B. , Nelson Steve , Summer Warren R. , Deaciuc Ion V. 
Published: April 2006

The hypothesis was tested that alcohol may modulate alveolar macrophage cytokine receptors, thus interfering in lung immune defense mechanisms. Male rats were treated with alcohol either acutely (7 hr continuous intravenous alcohol infusion at a rate of 30 mg/100 g body weight/hr after a priming dose of 175 mg/100 g body weight) or chronically (feeding an alcohol‐containing liquid diet for 12–14 weeks). Three hr before killing, the rats received an intravenous injection of Gram‐negative bacterial lipopolysaccharide (LPS; Escherichia coll, O26:B6, 100 μg/100 g body weight). After anesthesia with sodium pentobarbital, the trachea was cannulated, and the lungs excised and lavaged to obtain alveolar macrophages. The recovered cells were used to measure the binding of recombinant human [125I]tumor necrosis factor‐α (TNF‐α) and [125I]interleukin‐6 (IL‐6). Kd and Bmax, were determined at 4°C, thus reflecting only the cell‐surface binding sites and their affinity. Two binding sites were detected for both cytokines: high‐affinity (Kd1 in the range of 20–110 pM), low‐capacity (Bmax, in the range of 1–13 fmol/105 cells), and low‐affinity (Kd2 in the range of 0.6–1.3 nM), high‐capacity (Bmax2 in the range of 34–100 fmol/105 cells). Acute alcohol treatment significantly decreased Bmax1 (39%) and Bmax (79%) for TNF‐α, whereas chronic alcohol feeding abrogated the Bmax1 (Bmax1= 0), without affecting Bmax2. In the acute group, LPS had an effect similar to that of alcohol. Alcohol administration did not modify the LPS effects. The following changes were monitored for IL‐6 binding. Acute alcohol treatment markedly reduced (86%) Bmax2. LPS administration to saline‐infused group increased Kd1 (122%) and Bmax1 (197%), and significantly diminished (72%) Bmax2 These effects of LPS were not altered by alcohol administration, with the exception of Kd1 which was decreased (43%) by LPS administration to acutely, alcohol‐intoxicated rats. In the chronic treatment group, alcohol feeding increased Bmax2 (426%), an effect that was not modified by LPS injection.These data suggest that: (1) both acute and chronic alcohol administration to rats differentially affects the alveolar macrophage cell‐surface receptors for TNF‐α and IL‐6, and (2) alcohol‐induced alterations in these two cytokine receptors may in part mediate alcohol effects on lung immune defense.