bluuebunny/crossref_metadata_2025 huggingface dataset:
Human Placental Biotin Transport: Normal Characteristics and Effect of Ethanol
Authors: Schenker Steven , Hu Zhi‐Qiang , Johnson Raymond F. , Yang Yiqian , Frosto Teri , Elliott Byron D. , Henderson George I. , Mock Donald M.
Published: April 2006

Biotin, a vitamin essential for many metabolic reactions, is supplied to the fetus exclusively from the mother. Deficiency of biotin in pregnancy leads to impaired fetal growth and development. Alcohol taken in pregnancy likewise may cause fetal growth abnormalities. Normal biotin transport via the placenta and the effects of ethanol on this transport apparently have not been studied. Our aims were to characterize these phenomena for the normal human‐term placenta. Using maternal‐facing placental membrane vesicles, biotin uptake was sodium‐ and temperature‐dependent, saturable, and inhibited by structural analogs of biotin (desthiobiotin, biocytin, and biotin methyl ester), as well as by 4 and 10 hr exposure to 3 g/liter ethanol. Using the isolated perfused single cotyledon method to measure placental transport of biotin at a perfusion concentration of 1 nM, the overall rate of biotin transport was found to be only 30% that of antipyrine, a freely diffusible marker. Clearance of biotin was ∼2 ml/hr. g placenta, which was equal to the clearance of passively transferred l‐glucose; biotin clearance was similar in both maternal to fetal and fetal to maternal directions. Overall transfer of biotin from maternal to fetal compartments was not inhibited by 500‐fold greater concentrations of the three analogs, did not proceed against a biotin concentration gradient, and was not inhibited by 90–240 min exposure to an initial concentration of 4 g/liter ethanol. Concentration of biotin in the fetal compartment at the end of the study was not higher than on the maternal side (after maternal to fetal infusion), but placental concentration was 2‐ to 3‐fold greater. No significant metabolism of biotin was detected. Exposing human placental cultured trophoblast on day 3 to 24 hr of ethanol (2 g/liter) had no effect on the net uptake of biotin by these cells. These studies provide evidence that maternal‐facing placental membranes take up biotin by a mediated, carrier‐dependent process that is inhibited by ethanol; however, based on the perfusion studies, we conclude that the overall (maternal‐fetal) rate‐limiting transfer of biotin by the human placenta is most consistent with a passive process, which is not inhibited by short‐term exposure to ethanol.
Effects of Chronic Ethanol on Enzymes Regulating Sialylation and Desialylation of Transferrin in Rats
Authors: Ghosh Pradeep , Okoh Chitua , Liu Cling‐Hong , Lakshman M. R.
Published: April 2006

Transferrin is a N‐glycosylated glycoprotein and plays an important role in iron transport from sites of absorption and storage to sites of utilization. Chronic ethanol alters the normal microheterogeneity pattern of transferrin as a consequence of changes in the sialic acid content. However the underlying basis of this change in sialic acid contents of transferrin in alcohol abuse remains unclear. We have undertaken this study in order to investigate the effects of chronic ethanol in rats with respect to the hepatic rate of (i) transferrin synthesis based on labeled leucine incorporation, (ii) the incorporation of labeled N‐acetyl mannosamine (NAM) into sialic acid residues of transferrin, and (iii) roles of specific sialyltransferase and sialidase at hepatic subcellular level. The results showed no significant difference in the incorporation of labeled leucine into transferrin at all levels between the control and ethanol group, whereas the incorporation of NAM into transferrin was significantly decreased by 84% (p < 0.001) both at the whole cell and Golgi level. Thus, the incorporation of labeled NAM relative to the incorporation of labeled leucine into hepatic transferrin was significantly decreased by 86% (p < 0.001) in chronic ethanol‐treated animals as compared with the controls both at the whole cell and Golgi levels. These data are further supported by our finding of concomitant decrease in the activity of β‐galactoside α2,6‐sialyltransferase by 58% (p < 0.01) in ethanol‐treated rats as compared with control animals. In contrast, both the plasma membrane and plasma sialidase activities were increased by 95% (p < 0.01) and 85% (p < 0.01), respectively, in ethanol‐fed rats as compared with their respective controls. We conclude that decreased activity of sialyltransferase and increased activity of sialidase sequentially at the plasma membrane and plasma compartment may be responsible for decreased incorporation of sialic acid residues in serum transferrin molecules after chronic ethanol treatment.
Responding for Oral Ethanol after Naloxone Treatment by Alcohol‐Preferring AA Rats
Authors: Hyytiä P. , Sinclair J. D.
Published: April 2006

The present study examined the effect of a relatively nonselective opioid antagonist, naloxone, on lever pressing for oral ethanol by the alcohol‐preferring AA rats. The AAs, housed continually in operant chambers with free access to food and water, learned to respond for 10% oral ethanol during daily 60‐min alcohol access periods indicated by a stimulus light. The rats developed stable ethanol responding, resulting in mean ethanol intakes of 1.2 g/kg/60 min and measurable blood alcohol levels. In the first experiment, single systemic injections of naloxone (0.05–2.5 mg/kg) had no effect on the initial rate of responding; dose‐dependent decreases were observed later during the alcohol access. The second experiment examined the effects of repeated injections of 0.5 and 2.5 mg/kg naloxone on 5 consecutive days. Naloxone suppressed responding dose‐relatedly over the treatment days. In contrast to the effects of single injections, repeated injections with 2.5 mg/kg naloxone produced progressive decreases within the first minutes of access. The results suggest that naloxone may attenuate the reinforcing actions of ethanol.
Effects of Acute Ethanol Doses or Dietary Phenobarbitol with Carbon Tetrachloride Exposure on Vitamin A Status of Rats
Authors: Chapman Karen McCauley , Prabhudesai M. , Erdman John W.
Published: April 2006

Hepatotoxins such as ethanol and CCl4 are known to adversely affect vitamin A metabolism, although the effects of acute exposure to these agents have received less evaluation. The purpose of this study was to determine the effects on vitamin A status after a series of acute ethanol doses or a series of CCl4 inhalation challenges with concurrent phenobarbital exposure in the diet of rats. The depressed hepatic vitamin A seen after one ethanol dose was not sustained after repeated dosings. However, the significantly increased urine and liver radiolabeled vitamin A recovery after three acute ethanol exposure periods suggests adaptive physiologic and metabolic changes after the initial dose. The results of repeated CCl4/Phenobarbital dosings on vitamin A status paralleled, for the most part, the ethanol results. Thus, the initial acute exposure of hepatotoxic agents causes metabolic changes that are not fully sustained as the animal adapts to these challenges.
Effects of In Vitro Ethanol and Fetal Ethanol Exposure on Glutathione Stimulation of N‐Methyl‐D‐Aspartate Receptor Function
Authors: Weaver Melanie S. , Lee Young‐Hee , Morris Jimmy L. , Randall Patrick K. , Schallert Timothy , Leslie Steven W.
Published: April 2006

The present studies investigated the effects of glutathione (GSH; γ‐glutamylcysteinylglycine) and its oxidized form (GSSG) on neuronal N‐methyl‐D‐aspartate (NMDA) receptor activation in both acute and chronic preparations of ethanol exposure. It was demonstrated using fura‐2‐loaded dissociated brain cells from newborn rat pups that both GSH and GSSG (0–4 mM) produced concentration‐dependent increases in intracellular calcium similar to those produced by NMDA and other agonists of the NMDA receptor. GSH‐stimulated calcium entry was not inhibited by low intoxicating concentrations of ethanol, which contrasts with ethanol's typical inhibitory effect on NMDA‐stimulated receptor activation. Behavioral studies in adult rats demonstrated that ethanol‐induced sleep times were significantly decreased when 10 μl of GSSG (20 mM) were administered intracere‐broventricularly approximately 5 min before an intraperitoneal injection of 20% (w/v) ethanol (3 g/kg). These findings suggest that the less potent effect of ethanol on GSH‐stimulated calcium entry as well as the reduction in ethanol‐induced sleep times may be related to the presence of glycine in the peptide. The glycine found in GSH may activate the glycine site and block or reduce ethanol's action on this site. It appears that although GSH may play an important role in the activation of the NMDA receptor, this action does not involve a process that is sensitive to acute ethanol exposure. In contrast, when rat pups were chronically exposed to ethanol via prenatal exposure before the fura‐2 preparation, increases in NMDA‐ and GSH‐stimulated calcium entry were significantly decreased relative to those in pair‐fed and ad libitum‐fed controls. Thus, chronic in utero exposure to ethanol may alter the NMDA‐receptor complex, such that calcium entry mediated by NMDA or GSH activation is significantly reduced.
Ethanol‐Induced Suppression of Hippocampal Long‐Term Potentiation Is Blocked by Lesions of the Septohippocampal Nucleus
Authors: Steffensen Scott C. , Yeckel Mark F. , Miller Dawn R. , Henriksen Steven J.
Published: April 2006

Systemic ethanol increases synaptic inhibition and suppresses long term potentiation (LTP) in the dentate gyrus of the rat hippocampus. Local application of ethanol directly into the dentate gyrus of anesthetized rats increased the perforant path to dentate feed‐forward inhibition, but had no effect on LTP. Local application of ethanol to the medial septum, a subcortical structure with major input to the dentate, increased recurrent inhibition. Selective disruption of septodentate input produced by lesions of the septohippocampal nucleus blocked the effects of systemic ethanol on LTP. These findings are the first to demonstrate that septodentate input is necessary for ethanol to increase recurrent inhibition and suppress LTP in the dentate gyrus and suggest an important role for extrahippocampal modulation of both short‐ and long‐term plasticity in the hippocampus.
Investigation of the “Hangover” Effects of an Acute Dose of Alcohol on Psychomotor Performance
Authors: Lemon Jim , Chesher Gregory , Fox Allison , Greeley Janet , Nabke Claire
Published: April 2006

Performance on some complex and difficult tasks has been shown to be negatively affected for some time after an acute dose of alcohol has been cleared from the system. However, Dauncey reported impairment of a relatively simple reaction time task 3 hr after a dose of alcohol, when the blood alcohol concentration was at or near 0. This impairment was positively related to the subject's drinking history. A replication using the same task found a linear dose/impairment relationship during intoxication. A second simple reaction time task and a vigilance task showed a trend toward impairment, but only a divided attention task was significantly affected during intoxication. There was no significant effect of dose on any of these tests during a “morning after” session. The results are discussed in relation to the differences in method between Dauncey and this study.
Correlates of Alcohol Use Among Methadone Patients
Authors: El‐Bassel Nabila , Schilling Robert F. , Turnbull Joanne E. , Su Kuo‐Hsien
Published: April 2006

This study examines the predictors of alcoholism among 201 patients from three methadone maintenance treatment programs (MMTPs) in New York City. Using the Michigan Alcohol Screening Test, one‐fifth of the sample met criteria for alcohol dependence. Few subjects were currently enrolled in any form of chemical dependency treatment other than MMTP. Alcoholics started to use alcohol at an early age, and almost every alcoholic subject admitted to alcohol abuse before entering MMTPs. More alcoholics than nonalcoholics reported symptoms of somatization, obsessive‐compulsive behavior, depression, phobic anxiety, and psychosis. Logistic regression indicated that alcoholism among MMTP patients was associated with years drinking, years of sharing needles, utilization of drug abuse detoxification but not alcohol detoxification, smaller increases in methadone dosage over time, and psychiatric symptomatology. Findings are discussed in terms of their implications for designing more efficacious treatment approaches for dually addicted patients in MMTPs.
Elevated Plasma Homocysteine in Alcoholics
Authors: Hultberg B. , Berglund M. , Andersson A. , Frank A.
Published: April 2006

A significantly higher concentration of plasma homocysteine compared with controls was noted in a group of alcoholics (n= 42) hospitalized for detoxication. Normal concentrations of plasma homocysteine were reached within 1 or 2 weeks after admission to the hospital. In another group of abstinent alcoholics (n= 16) plasma homocysteine did not deviate from that of controls. Since hyperhomocysteinemia has been associated with premature vascular disease, we speculate that the increased plasma homocysteine in alcoholics might cause the increased incidence of stroke found in these patients.
Alcohol‐Induced Bone Disease: Relationship to Age and Parathyroid Hormone Levels
Authors: Bikle Daniel D. , Stesin A. , Halloran B. , Steinbach L. , Recker R.
Published: April 2006

Alcohol abuse leads to osteopenia and fractures. Epidemiological evidence suggests that older alcoholics are at substantially greater risk of fractures than younger alcoholics. To examine the interaction of age and alcohol abuse on bone mineral homeostasis, we studied 27 subjects with a history of 10 or more years of alcohol abuse ranging in age from 26–68 years. They were evaluated for disordered bone mineral homeostasis by assessing bone density (by quantitative computed tomography of the lumbar spine), histomorphometry of a transcortical biopsy from the iliac crest, serum levels of vitamin D metabolites and parathyroid hormone, and serum and urine levels of bone minerals. Seventeen of the subjects were found to have spinal compression fractures by routine radiologic procedures. The older the subject the more likely the subject was to have such a fracture. Bone densitometry indicated a marked reduction in spinal bone density with 15 subjects below 2 SD of normal aged‐matched controls. Bone density fell sharply with the age of the subject. Histomorphometry of iliac crest bone biopsies revealed no evidence of osteomalacia, but total resorption surfaces were increased. Consistent with the lack of osteomalacia were the normal levels of the vitamin D metabolites. The increased total resorption surfaces were correlated with high normal or elevated levels of parathyroid hormone as indicated both by radioimmunoassay and by urinary cAMP levels. Bone formation and active bone resorption (resorption surfaces containing osteoclasts) did not correlate with parathyroid hormone levels, however, but correlated negatively with age. Younger alcoholics tended to have increased bone remodeling, whereas older alcoholics tended to have suppressed bone remodeling out of proportion to the normal decline with age. We conclude that parathyroid hormone may play a role in stimulating bone resorption in younger alcoholics. With time the cumulative effects of alcohol abuse result in reduced bone resorption, as well as reduced bone formation, regardless of the levels of parathyroid hormone, ultimately leading to osteoporosis.
Ratings of Fetal Alcohol Syndrome Facial Features by Medical Providers and Biomedical Scientists
Authors: Abel Ernest L. , Martier Susan , Kruger Michael , Ager Joel , Sokol Robert J.
Published: April 2006

Medical providers, (obstetricians, pediatricians) and biomedical research scientists engaged in fetal alcohol research for many years evaluated facial photographs of newborns previously diagnosed clinically as having or not having fetal alcohol syndrome (FAS). Medical providers and biomedical scientists did not differ significantly in their ratings. Children independently diagnosed as having FAS were distinguished from non‐FAS children by both groups. Providing raters with additional information about children (e.g., birth weight) did not alter judgements significantly.

Raters were highly consistent in the ratings they assigned to children (r= 0.96). Accuracy was assessed using signal detection measures (e.g., likelihood ratio, d'). Based on these measures, the two occupational groups did not differ significantly, and rater accuracy was highly significant. Mean ratings were highly correlated with positive maternal Michigan Alcohol Screening Test scores (r= 0.84). These results suggest that the facial features associated with fetal alcohol exposure are readily identifiable, and this, in turn, implies that recognition problems need not be a major contributor to ascertainment of FAS.
Attention Allocation: Effects of Alcohol and Information Salience on Attentional Processes in Male Social Drinkers
Authors: Zeichner Amos , Allen Joseph D. , Petrie Charles D. , Rasmussen Paul R. , Giancola Peter R.
Published: April 2006

The purpose of this study was to examine the interactive effects of alcohol and salience of social cues (personality traits) on allocation of attention in the intoxicated male social drinker. It was expected that inebriated subjects would preferentially attend to high threat relative to low threat information contingent on the information's personal relevance. Seventy‐six participants received either alcohol or a placebo, or were in a control condition, and were given the opportunity to attend to personally salient or nonsalient positive, negative, and neutral information. Intoxicated participants viewed negative traits longer than did nonintoxicated subjects and attended to these traits longer in the salient than in the nonsalient condition. Findings are compared to the attention allocation model, and their implications for alcohol‐mediated cognitive processes are discussed.
Intravenous Flunitrazepam in the Treatment of Alcohol Withdrawal Delirium
Authors: Pycha Roger , Miller Carl , Barnas Christian , Hummer Martina , Stuppäck Christoph , Whitworth Alexandra , Fleischhacker W. Wolfgang
Published: April 2006

Alcohol withdrawal delirium (AWD) requires treatment with an adequate sedative, anticonvulsant, and antipsychotic agent next to general intensive care measures, Optimal medication should have a rapid onset of action and the possibility of parenteral application. A specific antagonist should be available. Flunitrazepam is a benzodiazepine that fulfills all these criteria.

Twenty five patients suffering from AWD (mean age 45 years) took part in an open trial and underwent treatment with infusions of flunitrazepam (concentration: 8 mg/250 ml NaCl; speed, 250 ml/hr). Psychopathological, vegetative, and vital parameters were assessed every hour.

All patients survived. They were treated with a mean total dose (SD) of 83.9 (45.4) mg of flunitrazepam (1.3 mg/kg body weight), which induced sedation 13.2 (5.3) min after the initiation of intravenous treatment. The mean duration of AWD (85.1 ± 39.4 hr) corresponded to other studies, whereas the frequency of preexisting and concomitant diseases was higher (92%) in our patients. A patient who suffered from bronchitis and had a nasopharyngeal tamponade showed severe respiratory depression after having received 4 mg of flunitrazepam. This complication remitted immediately when 0.5 mg of flumazenil was given intravenously. No epileptic manifestation was observed during the treatment or after discontinuation of flunitrarepam. Vegetative and psychopathological symptoms (tremor, sweating, hallucinations, confusion, and restlessness) remitted rapidly.

Our data suggest that intravenous flunitrazepam can be an efficacious and safe alternative to traditional treatment strategies of AWD.
Influence of Socially Desirable Responding in a Study of Stress and Substance Abuse
Authors: Welte John W. , Russell Marcia
Published: April 2006

Socially desirable responding is the reluctance to admit unpopular beliefs or behavior in order to avoid making a negative impression. It poses a problem for researchers who rely on self‐report of heavy drinking and drug use. The Marlowe‐Crowne Social Desirability Scale (SDS), which measures socially desirable responding, was administered to 1933 respondents in a general population survey. The relationships between SDS and various self‐report measures were examined. SDS was not correlated with gender or race; it increased with greater age and decreased with higher socioeconomic status. With age and socioeconomic status controlled, SDS had a moderate negative relationship with alcohol and drug use, and a strong negative relationship with variables reflecting the expression of anger, Correlations between drinking/drug use and such variables as age, marital conflict, and stressful life events were not substantially changed by controlling for SDS. It was concluded that social desirability response bias probably results in underestimates of rates of heavy drinking and drug use, but does not compromise the study of predictors of heavy drinking or drug use.
Simple Reaction Time Event‐Related Potentials: Effects of Alcohol and Sleep Deprivation
Authors: Krull Kevin R. , Smith Landgrave T. , Sinha Rajita , Parsons Oscar A.
Published: April 2006

The effects of two levels of alcohol intoxication and 30 hr of sleep deprivation on visual event‐related potential (ERP) waveforms concomitant to simple reaction time (RT) were examined in 54 normal male subjects. In a previous study, we reported that alcohol and sleep deprivation each increased RT. At a 0.05 breath alcohol concentration (BAC), the combined treatments produced an additive increase in RT, whereas at a 0.08 BAC the combined treatments produced no increase beyond that seen with each alone. In this study we present the ERP findings, Sleep deprivation alone increased the latency of a 150 msec negative component (N1) of the ERP. Alcohol increased the latency of a 250 msec negative component (N2), but only in the absence of sleep deprivation. Furthermore, this increased latency of N2 was correlated with RT measures. These results suggested that sleep deprivation slowed initial stimulus detection, whereas alcohol slowed later processing and response activation.
Sexuality of Alcoholic Women with Menstrual Cycle Function: Effects of Duration of Alcohol Abstinence
Authors: Gavaler Judith S. , Rizzo Alberto , Rossaro Lorenzo , Van Thiel David H. , Brezza Ennio , Deal Stephen R.
Published: April 2006

Although improvement in sexual function has been reported to occur in postmenopausal alcoholic women after long‐term sobriety, little is known about the role alcohol abstinence may play in terms of improving sexual functioning in alcoholic women with menstrual cycle function. The responses of 58 menstruating alcoholic italian women to a standardized questionnaire that included questions related to sexual function, behavior, and performance are reported. Women were categorized as alcohol abstinent (AA) for>1 year (long AA, n= 22) or < 1 year (short AA, n= 36). In both groups, 100% reported that they had a regular sexual partner, and the response rate to the sexuality questions was >99%. Compared with short AA women, long AA women were significantly older at the time of study, at menarche, and at onset of heavy drinking, alcohol dependence, and alcohol abstinence. Sexual desire was defined as willingness to engage in sexual activity; sexual capacity was defined as the ability to become sexually aroused; sexual responsiveness was defined as the ability to achieve orgasm. On all three measures, as well as intercourse frequency, both long AA and short AA women improved significantly with alcohol abstinence. These findings suggest that sobriety, even of relatively short duration, improves sexual function in menstruating alcoholic women.
Ethanol Alters Hormone Production in Cultured Human Placental Trophoblasts
Authors: Karl Peter I. , Fisher Stanley E.
Published: April 2006

Maternal alcohol abuse during pregnancy can lead to abnormalities in fetal development, including the fetal alcohol syndrome (FAS). Although intrauterine growth retardation is a hallmark of FAS, the pathophysiology is not fully understood. A contributing factor may be altered placental function, which could affect fetal growth and development. As a major endocrine organ during pregnancy, changes in the production of placental hormones could affect pregnancy and possibly fetal development. In this study, the effect of continued exposure to ethanol on placental hormone production was examined using cultured human placental trophoblasts. Ethanol exposure involved diffusion of ethanol from the atmosphere into the culture medium. This was refreshed daily, leading to daily peak concentrations of 280 to 300 mg/dl (60‐65 mM) at 16 to 24 hr. This ethanol exposure for 2 or 4 days significantly increased the production of human chorionic gonadotropin and progesterone by the cultured trophoblasts. However, ethanol treatment had no effect on human placental lactogen production. Acute stimulation (10 min) of cultured trophoblasts with adenosine (50 μM) normally results in increased production of cyclic adenosine 3′,5′‐monophosphate (CAMP). With ethanol exposure, adenosine‐stimulated cAMP production was significantly elevated relative to that in controls. However, the effect of ethanol on adenosine‐stimulated cAMP did not appear to be secondary to chronic alterations in adenosine in the culture medium. Measurement of adenosine in the culture medium revealed no difference in concentration or production between control and ethanol treated groups. Moreover, chronic (24 hr) pretreatment of trophoblasts with 0.2 to 10 μM additional adenosine before acute adenosine stimulation did not alter the cAMP response in either control or ethanol‐treated cells. This study demonstrates that ethanol exposure may alter placental production of hormones, specifically those that are cAMP dependent.
Sex Differences and the Effects of Alcohol on Immune Response in Male and Female Rats
Authors: Grossman C. J. , Nienaber M. , Mendenhall C. L. , Hurtubise P. , Roselle G. A. , Rouster S. , Weber N. , Schmitt G. , Gartside P. S.
Published: April 2006

Although it is clear that both alcohol and sex hormones impact immune function, very little information is available on the effects of alcohol on immune response in males versus females. We decided to determine if the alterations in immune response resulting from alcohol feeding might be expressed differently in males and females. To accomplish this we utilized pair‐fed male and female Sprague‐Dawley rats. Animals were fed a liquid diet for 60 days containing 30% of their calories as ethanol, and after 1 week this concentration was increased to 45% ethanol. Controls received liquid control diet of the same caloric and nutritional composition, and immune status was monitored with in vivo and in vitro techniques. Ethanol feeding significantly reduced the phytohemagglutinin skin response in males (p= 0.020) and females (p= 0.012). The concanavalin A blastogenic response of spleen cells prepared from female rats fed ethanol was significantly depressed with respect to spleen cells prepared from female rats fed the control diet (p= 0.0071). Alcohol also appeared to depress spleen cell blastogenic response in males, but this trend did not quite reach significance (p= 0.071). Spleen cells from groups of ethanol and control male and female rats were labeled with fluorescent monoclonal antibodies and run on a Fluorescent‐Activated Cell Sorter. Ethanol significantly increased the percentage population of CD4 (T‐helper cell) in males (p= 0.017), but not in females, and promoted an apparent, although nonsignificant, increase in the CD4/CD8 ratio in both sexes. An ELISA was used to measure IgM and IgG antibody elaborated by pokeweed mitogen‐stimulated spleen cells in cultures. Ethanol feeding increased both IgM secretion (p= 0.0001) and IgG secretion (p= 0.034) in cells from females but not males, and female cells secreted significantly more immunoglobins than did male cells.
Chronic Ethanol Ingestion Modifies the Renin‐Aldosterone Axis Independent of Alterations in the Regulation of Atrial Natriuretic Peptide
Authors: Wigle Dennis A. , Pang Stephen C. , Radakovic Nancy N. , Sarda Inder R. , Watson John D. , Roy Rabindra N. , Flynn T. Geoffrey
Published: April 2006

Using an animal model, we have investigated the effects of chronic ethanol ingestion on the regulation of atrial natriuretic peptide (ANP) synthesis and release. Male Sprague‐Dawley rats were maintained for 6 weeks on a liquid diet of ethanol (up to 20% v/v) as part of a 2% solution of calf milk replacer. Weight‐matched controls received an equal volume of ethanol‐free solution, and normal animals drank ad libitum. All animals received rat chow throughout the experiment. This model produced physiologically relevant levels of blood ethanol, as concentrations at the time of sacrifice were 171.98 ± 39.26 mg/dl. Plasma renin activity was significantly elevated in response to ethanol treatment, whereas circulating aldosterone concentration was reduced. No alterations in the plasma or atrial tissue levels of ANP were evident, although we did observe a significant increase in the ventricular tissue levels of ANP from 45.1 to 71.8 ng/g as a consequence of ethanol treatment. Levels of both atrial and ventricular ANP mRNA were not different between alcohol‐treated and liquid‐restricted control animals, although both groups showed significant increases in the amount of transcript in comparison with rats drinking ad libitum. No significant increases in either arterial blood pressure or heart/body weight ratio were observed for ethanoltreated rats. These results suggest that modifications in the reninaldosterone axis can occur independently of alterations in the regulation of ANP under the influence of chronic ethanol ingestion.
Effects of Postnatal Exposure to Alcohol on Reproductive Physiology and Sexually Dimorphic Behavior in a Marsupial, The Gray Short‐Tailed Opossum (Monodelphis domestica)
Authors: Fadem Barbara H.
Published: April 2006

The effects of postnatal exposure to alcohol on reproductive physiology and sexually dimorphic behavior and anatomy in adult male and female gray short‐tailed opossurns were examined. Female responsiveness to male pheromones and fertility in both sexes were essentially normal in postnatally alcohol‐treated animals. However, aspects of sexually dimorphic behavior were masculinized and defeminized in females and demasculinized in males following gonadectomy in adulthood and treatment with male (testosterone) or female (estradiol) hormones. The possible role of alterations in neural aromatase activity by perinatal alcohol exposure in mediating these behavioral effects and the potential use of this marsupial species in perinatal alcohol studies are discussed.
Dose‐ and Age‐Dependent Effects of Prenatal Ethanol Exposure on Hippocampal Metabotropic‐Glutamate Receptor‐Stimulated Phosphoinositide Hydrolysis
Authors: Queen Susan A. , Sanchez Christian F. , Lopez Samantha R. , Paxton Linda L. , Savage Daniel D.
Published: April 2006

Prenatal ethanol exposure reduces the density of the N‐methyl‐D‐aspartate (NMDA) receptor agonist binding sites and decreases the capacity to elicit long‐term potentiation (LTP) in hippocampal tormation of 45‐day‐old rat offspring. We hypothesized that prenatal ethanol exposure would reduce metabotropic‐glutamate receptor (mGluR)‐activated phosphoinositide hydrolysis also. Sprague‐Dawley rat dams were fed a liquid diet containing either 3.35% (v/v) ethanol or 5.0% ethanol throughout gestation. Control groups were pair‐fed either isocalorically matched 0% ethanol liquid diets or lab chow ad libitum. (1S,3R)‐1‐aminocyclopentane‐1,3‐dicarboxylic acid (trans‐ACPD) stimulated inositol‐1‐phosphate (IP1) accumulation via activation of the mGluR in offspring whose mothers consumed the 3.35% ethanol liquid diet was not different compared with the control groups. Furthermore, trans‐ACPD stimulated IP1 accumulation in 10 to 13‐day‐old offspring of the 5.0% ethanol diet group was not different compared with the control groups. However, trans‐ACPD stimulated IP1 accumulation was reduced significantly in 56‐ to 82‐day‐old offspring of dams fed the 5.0% ethanol liquid diet compared with the control groups. In contrast, bethanechol stimulated IP1 accumulation, mediated via activation of muscarinic cholinergic receptors, was not affected by maternal consumption of either ethanol liquid diet.

These results suggest both dose‐ and age‐dependent effects of prenatal ethanol exposure on hippocampal responsiveness to trans‐ACPD‐activated phosphoinositide hydrolysis. Furthermore, the ability of the 3.35% ethanol diet to alter hippocampal NMDA receptors without altering the mGluR response suggests a differential sensitivity to the effects of ethanol exposure in utero among hippocampal glutamate receptor subtypes. Recent studies indicate that activation of mGluRs facilitates NMDA receptor‐dependent LTP. Thus, higher blood ethanol concentrations achieved by consumption of the 5.0% ethanol liquid diet adversely affects an additional glutamate receptor mechanism associated with LTP. This additional effect may lead to an even greater impact of prenatal ethanol exposure on LTP than occurs when NMDA receptor function alone is affected by maternal consumption of more moderate quantities of ethanol.
Synthesis of Ventricular Mitochondrial Proteins In Vivo: Effect of Acute Ethanol Toxicity
Authors: Siddiq Tahir , Salisbury Jonathan R. , Richardson Peter J. , Preedy Victor R.
Published: April 2006

Most studies on the pathological responses of the heart to ethanol have been conducted in isolated systems. The objectives of this study were to determine (1) the synthesis rate of ventricular mitochondrial proteins in vivo and (2) whether the synthesis rates of these proteins are perturbed by acute ethanol exposure in vivo.

Fractional rates of protein synthesis [defined as the percentage of tissue protein renewed each day; i.e., ks (%/day)] were determined in male Wistar rats by in vivo injection of a flooding dose of L‐[4‐3H] phenylalanine. Subsarcolemmal mitochondria were released by polytron treatment, and the isolation of interfibrillar mitochondria involved treatment of the cardiac homogenate with the proteolytic enzyme Nagarse.

In the control rats mean ks values of 22.4%/day were observed for mixed cardiac proteins. The synthesis rates of subsarcolemmal and interfibrillar mitochondrial proteins were lower, i.e., 16.9%/day and 10.9%/day, respectively. Acute ethanol administration (75 mmol/kg body weight ip, 2.5 hr) depressed the fractional rate of protein synthesis in all cardiac fractions, including those pertaining to the mitochondria, as follows: mixed fraction—21%, p < 0.01; subsarcolemmal mitochondria—23%, p < 0.01; interfibrillar mitochondria—26%, p < 0.05; and nuclear fraction—20%, p < 0.05.

In conclusion, the reduced synthesis rate of the mitochondrial proteins in response to acute ethanol exposure may in some way be partly connected with the depression in myocardial contractility and associated functional damage of mitochondrial metabolism.
Comparison of Levels of Cytochromes P‐450, CYP1A2, CYP2E1, and Their Related Monooxygenase Activities in Human Surgical Liver Samples
Authors: Lucas Danièle , Berthou François , Dréano Yvonne , Lozac'h Patrick , Volant Alain , Ménez Jean‐François
Published: April 2006

Hepatic microsomal cytochromes P‐450 CYP1A2, and CYP2E1 contents and catalytic activities have been simultaneously investigated in 42 patients undergoing diagnostic liver biopsy. CYP1A2 contents, measured by Western blotting, were correlated with methoxyresorufin‐O‐demethylation and ethoxyresorufin‐O‐deethylation (r= 0.65 and r = 0.66, p < 0.001, respectively). CYP2E1 contents were correlated with 1‐butanol oxidation and 6‐hydroxylation of chlorzoxazone (r= 0.75 for both, p < 0.001). CYP1A2 catalytic activities varied by 30‐ to 40‐fold, whereas CYP2E1 activities varied by 6‐ to 20‐fold. In our study, these variations were not related to liver diseases or cancer of the digestive tract nor to alcohol drinking or smoking habits, because patients were alcohol‐ and tobacco‐free for 1 month before the study. Other environmental factors, diet habits, and/or genetic factors could explain the large interindividual variations observed.
Purification and Partial Amino Acid Sequence of a High‐Activity Human Stomach Alcohol Dehydrogenase
Authors: Stone Carol L. , Thomasson Holly R. , Bosron William F. , Li Ting‐Kai
Published: April 2006

To understand the relative importance of alcohol dehydrogenase (ADH) isoenzymes in gastric ethanol metabolism, a stomach‐specific ADH (σ‐ADH) was purified to homogeneity from human transplant donor and surgical tissues, and its activity for ethanol oxidation was examined. The enzyme from these tissues had a specific activity at pH 10 of ˜70 units/mg, about 10 times that reported by Moreno and Parés (J. Biol. Chem. 266:1128–1133, 1991). The enzyme exhibited a high Km for ethanol at pH 7.5 and 10 (29 and 5.2 mM, respectively). This high‐activity α‐ADH isoenzyme migrated on starch and isoelectric focusing gels to a position slightly anodic to the liver σ isoenzyme. It was subjected to digestion by endoproteinases, and ˜40% of the protein was sequenced. The σ‐ADH exhibited 75%, 68%, and 62% sequence identity to the human class I (β1), II (π), and III (χ) isoenzymes, respectively, and 61% identity to the deduced ADH6 amino acid sequence. Phylogenetic analysis indicated that precursors to this high‐activity σ‐ADH and the class I isoenzymes diverged more recently than precursors to the class II and III isoenzymes, after reptilian and avian divergence. The high‐activity σ‐ADH isoenzyme therefore represents a distinct class of ADH (class IV), more closely related in evolution to the class I isoenzymes than to the other known human isoenzymes.
Alcohol Consumption and Alcohol Pharmacokinetics: Interactions Within the Normal Population
Authors: Whitfield J. B. , Martin N. G.
Published: April 2006

We have analyzed the interrelationships between habitual alcohol consumption, peak blood alcohol concentration after a standard dose, and rate of alcohol metabolism in a group of 199 male and 213 female twins. Both peak concentration and rate of metabolism are strongly associated with alcohol consumption levels, even in the range of 0‐10 g of alcohol/day. The peak concentration and rate of metabolism were strongly correlated in both men and women; this is not due to their common dependence on alcohol intake nor to experimental error. These results show that the threshold for effects of habitual consumption on alcohol pharmacokinetics is much lower than previously suspected, and that there are factors that reduce preabsorptive or first‐pass metabolism but increase postabsorptive metabolism.
Gender Differences in Lifetime Psychiatric Disorders Between Sons and Daughters of Alcoholic Mothers: A Pilot Study
Authors: Bidaut‐Russell Michelle , Smith Elizabeth M. , Bradford Susan E.
Published: April 2006

Lifetime prevalence of selected psychiatric disorders was assessed in 24 independent pairs of adult siblings (brother‐sister) with an alcoholic mother, using the Diagnostic interview Schedule. Adult females were as likely as adult males to have had one or more lifetime diagnosis of psychiatric disorder. Lifetime prevalence of affective disorders was the same in male and female siblings. Although not statistically significant, compared with their sister, men were 3 times more likely to have had a diagnosis of alcohol abuse/dependence, and 3.5 times more likely to have had a diagnosis of general anxiety disorder. When compared with their brother, women were 1.66 times more likely to have had a diagnosis of drug abuse/dependence, 3 times more likely to have had a diagnosis of panic disorder, and 6 times more likely to have been diagnosed with phobia; however, these differences were not significant.
Drinking During Pregnancy Decreases Word Attack and Arithmetic Scores on Standardized Tests: Adolescent Data From a Population‐Based Prospective Study
Authors: Streissguth Ann P. , Barr Helen M. , Olson Heather Carrnichael , Sampson Paul D. , Bookstein Fred L. , Burgess Donna M.
Published: April 2006

Women (1529) were interviewed in midpregnancy, and a cohort of their children has been examined at various ages. The two standardized tests presented herein are part of a large battery of tests administered when the children were 14 years old. “Word Attack” (n=462) measures phonological processing on a task involving the reading of pseudowords in nontimed performance. “Arithmetic” (n=191) measures auditorily processed mental computations in timed performance. Scores on both tests were associated with prenatal alcohol exposure in a dose‐dependent fashion. These effects were robust when considered in relation to a wide variety of potentially confounding variables, such as prenatal exposure to tobacco and other drugs, sociodemographic characteristics, and traumatic postnatal events. A variety of alcohol scores were related to these two performance measures, but those involving a massing of drinks on a given occasion had the strongest association. The higher the average number of drinks/occasion, the poorer the offspring performance on tasks thought to underlie numerical problem solving and reading proficiency. Earlier reports of prenatal, alcohol‐related neurobehavioral deficits in childhood have now been extended into adolescence.
Abuse of Alcohol in Sudden Out‐of‐Hospital Deaths in Finland
Authors: Perola Markus , Vuori Erkki , Penttilä Antti
Published: April 2006

Alcoholism is known to be greatly underdiagnosed in death certificates, a fact that biases in estimates of alcohol‐related mortality. An autopsy series of 1658 cases (920 with natural cause of death and 738 nonnatural) was reviewed to evaluate the extent of this bias, and also to see how well different sources of information served as indicators of alcoholism when alcohol‐related disease diagnosed at autopsy was considered as a gold standard. A stepwise logistic regression model adjusted by age and sex showed police reports of individual's alcohol usage and blood alcohol concentration (BAC) of >2.9‰ at autopsy to be the two most significant predictors of chronic alcohol abuse (p < 0.0001). The specificities of these two parameters as predictors of chronic alcohol abuse were generally high and sensitivities low. The authors see high BAC (>2.9‰), due to its high specifity, as particularly suggestive of chronic heavy drinking. However, it is wise to use these parameters only as an aid in decision‐making, not as sole indicators of alcoholism. Deaths associated with chronic heavy drinking were frequent, 50.5% of the total series (male 56.4%, female 37.1%). For all but one age‐group (male 45‐64 years), however, death certificates mentioned alcoholrelated diseases in less than half of these cases. Especially evident underdiagnosis was found for female and males 65 years and older. These results indicate that alcoholism is frequent in such a highly selected population as a series of forensic autopsies and suggest that estimates of prevalence of alcoholism based only on review of death certificates are to be considered with great caution. It is also suggested that alcoholism may have a role in more female deaths than is generally thought.
Injury Type, Injury Severity, and Repeat Occurrence of Alcohol‐Related Trauma in Adolescents
Authors: Maio Ronald F. , Portnoy Joel , Blow Frederic C. , Hill Elizabeth M.
Published: April 2006

Injury associated with alcohol use is a significant problem among adolescents; however, routine evaluation of alcohol use in this population is not conducted. The purpose of this study was to compare injured adolescents presenting to an emergency room with a positive serum alcohol concentration (SAC+) with those injured adolescents wlth a negative serum alcohol concentration (SAC‐). Data were collected retrospectively on 176 injured patients, between the ages of 13 and 18, consecutively admitted to a university hospital from January 1, 1989‐December 31, 1990. Information collected included mechanism and severity of injury, outcome, SAC, length of stay, prychiatric history, prior or subsequent admission for injury, and hospital charges. Of those tested with an SAC, more than one‐third had a positive SAC. Patients with positive SACs had a greater probability of having a psychiatric history and more frequently had a prior or subsequent injury. Furthermore, only 34% of SAC+ patients were referred for counseling. The results indicate that a SAC should be obtained on all adolescents admitted for trauma, that adolescents presenting with injuries and a positive SAC should be referred for alcohol and psychiatric assessment, and that injured adolescents may be at increased risk for repeat injuries in the future.
Hypothalamic‐Pituitary‐Thyroid (HPT) Axis in Chronic Alcoholism. I. HPT Axis in Chronic Alcoholics During Withdrawal and After 3 Weeks of Abstinence
Authors: Baumgartner Andreas , Rommelspacher Hans , Otto Monika , Schmidt Lutz G. , Kürten Irene , Gräf Klaus‐Jürgen , Campos‐Barros Angel , Platz Werner
Published: April 2006

Thyroxine (T4), free T4 (fT4), triiodothyronine (T3 free T3 (fT3), reverse T3 (rT3), thyrotropine (TSH), thyroxine binding globulin (TBG), and T3 uptake were measured in 14 chronic alcoholics during withdrawal and after 21 days of abstinence. Results were compared with those of 16 healthy volunteers. During withdrawal, the fT4 and fT3 concentrations were subnormal, whereas the respective protein‐bound fractions were normal. T4, T3, and TBG increased during the abstinence period, T3 and TBG being significantly higher than in normals at the second measuring time. T3 uptake values fell, but remained well within the normal range at both measuring times. During abstinence, the fT3 levels remained significantly lower than in healthy subjects. rT3 concentrations decreased, but not significantly. The TSH values were normal throughout.

These results showed numerous abnormalities in the hypothal‐amic‐pituitary‐thyroid axis in alcoholics, the reasons for which are as yet unclear. The following possible interpretations are suggested: 1. The abnormally low serum fT3 and ff4 levels during withdrawal might reflect an increase in tissue uptake. 2. The increases in T4‐and partty those in T3‐during abstinence seem to reflect increased binding by TBG, the level of which rose markedly for reasons as yet unknown. 3. If increases in TBG during abstinence are taken into account, the decreases in rT3 concentrations may reach the level of statistical significance. These falls in rT3 concentrations may reflect an increase in rT3 metabolization (deiodination) in various tissues, including the CNS, leading to a reduction in serum rT3 bioavail‐ability. 4. Factors such as liver disease, protein caloric malnutrition, and “psychological stress” do not fully explain all these abnormalities. A direct effect of ethanol on intracellular thyroid hormone metabolism and/or function seems conceivable.