bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Ethanol on Insulin‐Like Growth Factor‐II Release from Fetal Organs
Authors: Mauceri Helena J. , Lee Wei‐Hua , Conway Sonya 
Published: April 2006

This study examines the effect of ethanol (ETOH) exposure and nutrient restriction on the release of insulin‐like growth factor (IGF)‐II from 18‐ and 20‐day explanted fetal organs. Fetuses were exposed to ETOH (E) in utero by feeding dams a 36% (calories derived from ETOH: 6.6% v/v) ETOH liquid diet. Control fetuses were offsprings of dams either pair‐fed (P) a control liquid diet or ad libitum (A) fed a standard pelleted lab chow. Brain, heart, kidney, liver, lung, muscle, and placenta of fetuses from the same litter were pooled and explanted, and IGF‐II concentration in explanted media was analyzed by radioimmunoassay. Maternal and fetal weights were determined during pregnancy and at sacrifice, respectively, to evaluate the influence of ETOH on growth.Both maternal and fetal weights were substantially reduced by ETOH on 18 and 20 days of gestation compared with both A and P controls. At 18 days of gestation, E fetuses (1.33 ± 0.03 g) weighed less than either A (1.47 ± 0.03 g) or P (1.54 ± 0.04 g) fetuses. By 20 days, A mean fetal weight (4.19 ± 0.23 g) was significantly greater than both P (3.74 ± 0.06 g) and E (3.28 ± 0.06 g) fetuses. IGF‐II concentration in media from 18‐day fetal explants was highest from E (brain, heart, liver, and placenta) and P tissues (kidney, lung, and muscle). IGF‐II in media from A tissues (except placenta) was lower than both E and P levels. A significant difference between treatments occurred in heart. By 20 days, IGF‐II levels were highest in media from all A tissues (except placenta). IGF‐II in media from E tissues (except lung) was lower than those from P tissues. A significant difference between treatments occurred in the brain.With regard to the developmental pattern, IGF‐II release generally increased between 18 and 20 days of gestation, with the greatest increases occurring in A tissues. Increased secretion by P tissues was greater than that by corresponding E tissues, and tended to follow the A trend. On the other hand, E brain, kidney, and placenta released only slightly more IGF‐II at 20 days compared to 18 days, whereas E heart, liver, lung, and muscle released slightly less hormone.This study suggests that even moderate nutrient deprivation influences the pattern of IGF‐II release from fetal organs, even though there is only a small decrease in overall body size. At the same level of nutrient deprivation, ETOH more dramatically alters both fetal weight and the pattern of IGF‐II release. Because IGFs are autocrine/ paracrine factors that influence growth, differentiation, and function, the reduced availability of IGF‐II may be one of the factors contributing to ETOH‐induced growth retardation and impaired functional capacity of some organ systems.
Fine T‐Cell Subsets in Alcoholics as Determined by the Expression of l‐Selectin, Leukocyte Common Antigen, and β‐Integrin
Authors: Cook Robert T. , Waldschmidt Thomas J. , Ballas Zuhair K. , Cook Brian L. , Booth Brenda M. , Stewart Barbara C. , Garvey Michael J. 
Published: April 2006

Alcoholics admitted to the hospital solely for detoxication have been studied by flow cytometry to evaluate changes in the surface markers of peripheral blood leukocytes. As we have shown previously, such patients have an elevated percentage of CD8hl lymphocytes that are HLA DR+; we now demonstrate that they also have striking alterations in the quantitative relationships of the fine T‐cell subsets. Both CD4+ and CD8hl lymphocytes have a sharply reduced percentage of the l‐selectin+ CD45RA+ subset, increased percentages of the CD45RA‐subsets, and several other fine subset alterations. The fine subset profile suggests, according to current correlations of phenotype and function, that both CD4+ suppressor inducer and CD4‐dependent CD8+ suppressor effector cells are reduced, whereas other subsets, including CD8+ CTL or their precursors, are increased in relative percentages. Some of the phenotypic changes are reversible over the several days following withdrawal.In other results, the percentage of CD8hl lymphocytes expressing CD11b (β‐integrin) is shown to be reciprocal with the percentage expressing l‐selectin both in normals and alcoholics. However, the regression function of CD11b vs. l‐selectin on CD8hl cells is different for the alcoholics than for the normals, indicating an abnormality in the regulation of the expression of these two adhesion markers. Taken together, this abnormality of adhesion molecules and the fine subset alterations previously described indicate widespread changes in the peripheral lymphocytes of currently drinking alcoholics. These changes suggest functional deficiencies that may include alterations of lymphocyte traffic and other adhesion‐dependent functions, and a shift in the balance of regulatory interactions.
Acetate‐Mediated Effects of Ethanol
Authors: Israel Y. , Orrego H. , Carmichael F. J. 
Published: April 2006

Ethanol has been shown to increase markedly portal blood flow, primarily by increasing intestinal blood flow. This effect of ethanol is reproduced by acetate, infused at rates equivalent to those leading to endogenous acetate production following ethanol administration. The physiological mediator, adenosine, is also known to increase markedly intestinal and portal tributary blood flow. We have shown that adenosine receptor blockade with 8‐phenyltheophylline completely abolishes the effects of ethanol, acetate, and adenosine on intestinal and portal blood flow, suggesting that increases in adenosine tone may constitute a common mechanism mediating the actions of both ethanol and acetate on the splanchnic vasculature.Studies are also presented that show that acetate administration has marked effects on central nervous system function. On two tests, motor coordination and anesthetic potency, both ethanol and acetate showed similar effects. The effects of acetate were fully abolished by 8‐phenyltheophylline. The effects of ethanol were partially blocked by 8‐phenyltheophylline, with a greater effect of this blocker being seen at low doses of alcohol.Whereas ethanol at low doses increased locomotor activity in mice, acetate markedly reduced it. The effect of acetate on locomotion was fully reversed by the adenosine receptor blocker 8‐phenyltheophylline, whereas the activating effect of ethanol on locomotion was markedly enhanced by this blocker. These data suggest that the actions of ethanol on locomotor activity normally result from the combination of a direct stimulatory effect of ethanol per se and an inhibitory effect of acetate, produced endogenously from ethanol. When the latter effect of acetate is abolished by adenosine receptor blockade, the activating effect of ethanol is fully expressed.These data demonstrate that acetate is not an inert molecule and that some actions of ethanol may be partially or fully mediated by acetate.
Carbohydrate‐Deficient Transferrin and γ‐Glutamyltransferase as Markers of Heavy Alcohol Consumption: Gender Differences
Authors: Anton Raymond F. , Moak Darlene H. 
Published: April 2006

Carbohydrate‐deficient transferrin (CDT) has been described as a more specific and sensitive marker of recent heavy alcohol consumption as compared with the current tests now available, such as γ‐glutamyltransferase (GGT). Most of the data generated from European populations have not compared the utility of CDT and GGT in the detection of heavy alcohol consumption as a function of gender. We examined the ability of both CDT and GGT to discriminate between 42 men and 18 women with heavy alcohol consumption (>60 g/day) admitted to an alcohol detoxification center and a group of controls matched for age, race, and gender. CDT was higher, but GGT lower, in control females compared with males. Both CDT and GGT were higher in patients of both genders. At specificities >90%, the sensitivity of CDT for detecting male alcohol abusers was 79% and for female alcohol abusers 44%. For GGT, the sensitivities were 65% and 44%, respectively. When both tests were used simuttaneously, the sensitivity for the detection of alcohol abusers increased to 95% for males and 72% for females. Receiver Operator Characteristic analysis tended to confirm the superiority of CDT over GGT in the detection of heavy alcohol consumption in males, but not in females. A positive relationship was found between serum iron levels and CDT in control females but in no other group.The concordant findings of this American study with those in similar French and Finnish clinical populations, utilizing similar assay techniques, suggest that the measurement of CDT is clinically more useful than GGT in detecting recent heavy alcohol consumption in males. Because serum CDT and GGT levels appear to be independently associated with heavy alcohol consumption, their combined measurement should increase the sensitivity of detection of this condition.
Hormonal Derangements in Patients with Severe Alcohol Intoxication
Authors: Hirschl Michael M. , Derfler Kurt , Bieglmayer Christian , Roggla Hannelore , Zeiner Andrea , Seidler Dan , Laggner Anton N. 
Published: April 2006

Controversial results of fluid and electrolyte derangements in patients with moderate alcohol intoxication have been described. However, no information is available about severe alcohol intoxication. We investigated differences of hormonal disorders between alcohol‐habituated and alcohol‐naive subjects with severe ethanol intoxication. The hormonal derangements and recommendations on therapy of these patients are discussed.Thirty‐three patients [10 alcohol‐naive (group A) and 23 alcohol‐habituated (group 8) subjects] with severe alcohol intoxication (blood ethanol > 200 mg/dl) were selected for the study. Electrolytes and osmolarity of serum and urine, blood ethanol, vasopressin, renin, and aldosterone were determined on admission 2, 4, and 6 hr later. Fluid balance was calculated for each hour. All patients received isotonic saline solution according to urine production.Group A: On admission, serum osmolarity was increased (308 mOsmol/kg). Concomitantly, vasopressin level was elevated on admission (9.12 pglml). Increased serum osmolarity was correlated with elevated vasopressin levels (r= 0.8211; p < 0.005). Serum electrolytes, renin, and aldosterone values were within normal ranges.Group B: On admission, vasopressin level was significantly decreased (0.9 pg/ml), despite an elevated serum osmolarity (309 mOsmol/kg). Serum osmolarity remained high despite a sufficient fluid substitution. In addition, vasopressin level remained suppressed over the observation period. Aldosterone level was significantly increased on admission (319 ng/ml). Accordingly, serum sodium was increased from 142 to 148 mM/liter, and serum potassium was decreased from 3.9 to 3.4 mM/liter.Response to hyperosmolality due to severe alcohol intoxication is different in alcohol‐naive and alcohol‐habituated subjects. In contrast to alcohol‐naive subjects, vasopressin secretion of alcohol‐habituated subjects was suppressed rather than elevated despite hyperosmolality. Additionally, in these patients, hyperaldosteronism was observed leading to hypernatremia and hypokalemia. Therefore, infusions containing sodium should be avoided in alcohol‐habituated patients.
Helicobacter Infection and Gastric Ethanol Metabolism
Authors: Salmela Katja S. , Salaspuro Mikko , Gentry R. Thomas , Methuen Taina , Höök‐Nikanne Johanna , Kosunen Timo U. , Roine Risto P. 
Published: April 2006

The organism frequently colonizing the stomach of patients suffering from chronic active gastritis and peptic ulcer disease–Helicobacter pylori–possesses marked alcohol dehydrogenase (ADH) activity. Consequently, Helicobacter infection may contribute to the capacity of the stomach to metabolize ethanol and lead to increased acetaldehyde production. To study this hypothesis, we first determined ADH activity in a variety of H. pylori strains originally isolated from human gastric mucosal biopsies. ADH activity was also measured in endoscopic gastric mucosal specimens obtained from H. pylori‐positive and ‐negative patients. Furthermore, we used a mouse model of Helicobacter infection to determine whether infected animals exhibit more gastric ethanol metabolism than noninfected controls.Most of the 32 H. pylori strains studied possessed clear ADH activity and produced acetaldehyde. In humans, gastric ADH activity of corpus mucosa did not differ between H. pylori‐positive and ‐negative subjects, whereas in antral biopsies ADH activity was significantly lower in infected patients. In mice, gastric ADH activity was similar or even lower in infected animals than in controls, depending on the duration of infection, despite the fact that the infectious agent used–Helicobacter felis–showed ADH activity in vitro. In accordance with this, Helicobacter infection tended to decrease rather than increase gastric ethanol metabolism in mice. In humans, it remains to be established whether the observed decrease in antral ADH activity associated with H. pylori infection can lead to reduced gastric first‐pass metabolism of ethanol.
Longitudinal Observations of Monoamine Oxidase B in Alcoholics: Differentiation of Marker Characteristics
Authors: Rommelspacher Hans , May Torsten , Dufeu Peter , Schmidt Lutz G. 
Published: April 2006

The marker characteristics of monoamine oxidase B (MAO B) in human platelets were investigated in a clinical study of 59 alcoholics (diagnosed according to the criteria of ICD‐10) observed over a period of 6 months. Demographic and family history were obtained by a structured interview, including the substance abuse section of CIDI (Composite International Diagnostic Interview). The patient's personality was assessed by Cloninger's Tridimensional Personality Questionnaire (TPQ). Blood samples were first drawn during chronic intoxication (day of admission to the hospital for detoxication), after short‐term abstinence (8 days later), medium‐term (3 months later), and long‐term abstinence (6 months later).A group of 22 matched healthy nonalcoholics served as controls studied under sober conditions and during acute intoxication (4 hr after ingestion of 1 g ethanol/kg body weight). All platelet samples were investigated with 6 kynuramine concentrations as substrate (fluorometric assay) in the absence and presence of 200 itim ethanol (ETOH) in vitro.MAO B activity was significantly reduced in alcoholics during chronic intoxication (Vmax: 2.70 ± 0.15 nmol/min/mg protein) compared with sober (Vmax: 3.25 ± 0.23 nmol/min/mg protein) and acutely intoxicated controls that turned to normal during abstinence. However, MAO B activity obtained during medium‐ and long‐term abstinence was significantly lowered in patients with high novelty‐seeking and impulsiveness scores in the TPQ, a history of suicide attempts, or an alcoholic mother. The affinity of MAO B (Km values) was unchanged in alcoholics at any time investigated. Addition of ETOH in vitro reduced the affinity. This effect was less pronounced when the blood had been obtained during chronic intoxication and after short‐term abstinence, suggesting tolerance toward ETOH.It is demonstrated that reduced MAO B values may serve as state and trait markers of alcoholism and that they can be disentangled in a longitudinally designed study.
Prenatal Ethanol Exposure: Susceptibility to Convulsions and Ethanol's Anticonvulsant Effect in Amygdala‐Kindled Rats
Authors: Kim C. Kwon , Dalal Suntanu , Pinel John P. J. , Weinberg Joanne 
Published: April 2006

The present experiments assessed the effects of prenatal ethanol exposure on the susceptibility to convulsions and on the anticonvulsant effect of ethanol using the electrical kindling model of epilepsy in rats. Adult male Sprague‐Dawley rats from prenatal ethanol (E), pair‐fed (PF), and ad libitum‐fed control (C) treatment groups were tested following the implantation of a stimulation electrode in the left amygdala complex. The same rate viete tested in tout consecutive experiments.Both E and PF rats showed a slightly slower rate of kindling than C rats, as measured by convulsion class but not as measured by forelimb clonus duration (experiment 1). However, the groups did not differ significantly in the electrical stimulation threshold for kindled convulsions (experiment 2). Furthermore, prenatal ethanol exposure had no significant effect on the dose‐response curve for ethanol's (0, 0.9, 1.1, 1.3, and 1.5 g/kg, ip) anticonvulsant effect (experiment 3), or on the rate of tolerance development to ethanol's (1.5 g/kg, ip) anticonvulsant effect (experiment 4) on kindled convulsions. Thus, prenatal exposure to ethanol does not appear to have long‐term effects on the susceptibility to convulsions or on the anticonvulsant effect of ethanol in adult male rats in the kindling model as used in the present experiments.
Effects of Cerebral Electrical Stimulation on Alcoholism: A Pilot Study
Authors: Padjen A. L. , Dongier M. , Malec T. 
Published: April 2006

Cerebral electrical stimulation (CES), born from research on electroanesthesia in the seventies, consists of the application of a pulsating current of small intensity (usually less than 1 mA, and below the threshold of perception) through the skull, e.g., in daily 30‐min sessions.Claims of biological effectiveness (neurochemical, hormonal and EEG changes, naloxone‐reversible analgesia in rats, etc.) and of clinical effectiveness (anxiety, depression, cognitive functions in alcoholics) have often relied on poorly controlled data. A recent controlled study in the treatment of opiate withdrawal has been positive. The present double‐blind controlled study compares active CES with sham stimulation in 64 alcohol‐dependent males. Over 4 weeks, both treatment groups improved significantly in most aspects. In the active treatment group additional significant improvement was observed in week‐end alcohol consumption, and in two psychological measures: depression and stress symptoms index, but not in general drinking behavior.
Hon v. Stroh Brewery Company: What Do We Mean by “Moderate” and “Heavy” Drinking?
Authors: Abel Ernest L. , Kruger Michael L. 
Published: April 2006

Although widely used, drinking terms such as “light,”“moderate,” and “heavy” are unstandardized and, as a result, public health messages using these terms may convey confusing information. As an initial attempt in providing such standardization, the present study surveyed public definitions for these terms. “Light” drinking was operationally defined as 1.4–2.4 drink/day; “moderate” drinking was defined as 2.5–3.6 drink/day; and “heavy” drinking was defined as 3.7 drinks/day and above. These ranges, however, were dependent on the respondent's gender, age, socioeconomic status, and especially the respondent's self‐reported tolerance. Males had a higher threshold of consumption for “moderate” and “heavy” drinking than women. Older respondents likewise assigned a higher threshold for these terms than younger respondents. As respondent income increased, the threshold for “heavy” drinking decreased. The heaviest drinkers had a higher threshold for assigning the “heavy” label than did any other group. Ethnicity did not significantly affect these ranges, and religion only affected the threshold for “heavy” drinking.Because researchers ultimately rely on terms such as “moderate” or “heavy” to communicate their findings to colleagues and the public, it would seem apposite for them to agree on operational definitions for such terms. It would also seem appropriate to consider the operational definitions the public uses when referring to these terms to promote credibility of research findings and appropriate changes in behavior.
Generation of Neurons in the Rat Dentate Gyrus and Hippocampus: Effects of Prenatal and Postnatal Treatment with Ethanol
Authors: Miller Michael W. 
Published: April 2006

Neurons in the rat hippocampal formation (the dentate gyrus and the hippocampus) are born over a protracted period, from gestational day (G) 15 into adulthood. Dentate gyral neurons born prenatally are generated from the ventricular zone, whereas those born postnatally are derived from a secondary proliferative zone, the intrahilar zone. In contrast, hippocampal pyramidal neurons are generated only prenatally from the ventricular zone. In the neocortex, ethanol depresses the proliferation of cells in the ventricular zone and stimulates the proliferation of cells in the secondary proliferative zone. The present study tests the hypotheses that prenatal treatment with ethanol has a different effect on the generation of dentate gyral neurons than does postnatal ethanol treatment, and that these differences are determined by the timing of the ethanol exposure relative to the period and site of neuronal generation.Rats were treated with ethanol between G6 and G21 or between postnatal day (P) 4 and P12. They were given an injection of [3H]thymidine on G15, G18, G21, P6, P9, or P12. Rats were killed on P30–P35. The tissue was processed by standard autoradiographic methods and assessed using rigorous stereological procedures. The total number of neurons and the density of radiolabeled neurons in both the dentate gyrus and the CA1 region of the hippocampus were determined.Prenatal ethanol treatment decreased the total number of neurons in the CA1 segment of the hippocampus and had little impact on neuronal number in the dentate gyrus. Likewise, the number of hippocampal and dentate gyral neurons generated daily was significantly lower in ethanol‐treated rats than in controls. Postnatal treatment to ethanol, however, significantly increased the total number of dentate gyral neurons and the density of neurons generated postnatally. These postnatal changes depended on the blood ethanol concentration (BEC). At moderate BECs, the total number of neurons in the dentate gyrus and the number of neurons generated was increased. At high BECs, however, neuronal number and neuronal generation were decreased. Postnatal ethanol treatment had no effect on the number of (total or radiolabeled) CA1 neurons.Thus, pre‐ and postnatal exposure to ethanol have opposite effects both on the number of neurons in the dentate gyrus and on the generation of neurons. These paradoxical effects likely result from three causes: the differential effects of ethanol on the two proliferative zones, the critical period of neuronal development, and the potentially opposite effects of moderate and high BEC.
Computational Modeling of a Putative Fetal Alcohol Syndrome Mechanism
Authors: Whitmire David , Bowen J. Phillip , Shim Joong‐Youn , Whitmire Paula S. 
Published: April 2006

Fetal alcohol syndrome (FAS) refers to a pattern of birth defects occurring in a subpopulation of children born to women who consume alcohol during pregnancy. The significant medical, social, and economic impact of FAS is increasing. Particularly hard‐hit are African‐American and native‐American women and children. Over the past two decades, basic and clinical research produced voluminous data on ethanol effects on developing organisms. In 1991, Duester and Pullarkat proposed that competition of ethanol with retinol at the alcohol dehydrogenase (ADH) binding site formed the basis of the FAS mechanism. This competition adversely affects the developing fetus caused by deregulation of retinoic acid (RA) homeostasis essential for proper fetal tissue development. Stated concisely, the FAS hypothesis is:

Class I ADH catalyzes the rate‐limiting step in oxidation of retinol (ROH) to RA, and ethanol (ETOH) to acetic acid, thus establishing competition for ADH between ROH and ETOH.
RA is required as a signal molecule for cell differentiation critical for normal fetal morphogenisis.
ADH binds ingested ETOH, thus deregulating RA homeostasis leading to improper RA signal transduction.

Preliminary results from molecular modeling studies of ROH‐ADH and ETOH‐ADH structures, and physiologic pharmacokinetic modeling confirm the hypothesis with remarkable fidelity.