bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic Influences on Craniofacial Outcome in an Avian Model of Prenatal Alcohol Exposure
Authors: Su Birong , Debelak Katherine A. , Tessmer Laura L. , Cartwright Martina M. , Smith Susan M. 
Published: April 2006

Background: Understanding the basis for ethanol's teratogenic effects may inform the etiology of fetal alcohol syndrome. Here we investigate how genetic background and susceptibility to ethanol‐induced neural crest apoptosis contribute to the distinctive craniofacial phenotype observed after prenatal alcohol exposure.Methods: Nine different chick strains were exposed to ethanol at gastrulation. The sensitivity of these embryos to ethanol‐induced neural crest apoptosis was reported elsewhere (Debelak and Smith, 2000). Here, these embryos were permitted to develop until embryonic day 10, when facial morphogenesis was largely complete, and cephalometric measurements were made on cleared skulls. Shifts in facial growth were correlated against the severity of ethanol‐induced apoptosis in facial precursors.Results: The facial shape produced by ethanol exposure was a function of the embryos’ genetic strain. Three general responses were observed: apparent midfacial flattening (Babcock B300 x Hampshire Red, ISA‐Babcock, HyLine W98, and HyLine W36 strains), overall facial expansion (Spafas and Babcock B300 strains), or overall facial hypoplasia (DeKalb strains). When dose and timing of exposure were held constant, the embryo's genetic background predicted the facial outcome. For ethanol‐sensitive strains, apoptosis of facial precursor populations was required to produce the facial defects. That some strains had essentially normal faces despite extensive cell death indicated a capacity to recover from the earlier neural crest losses.Conclusions: We propose that ethanol's effects on craniofacial development are multifactoral, and these influences may include susceptibility to apoptosis, regenerative capacity, and compensatory outgrowth of the facial primordia. The embryo's genetic background may modulate these events. The high and low responder chick strains are useful tools to dissect these contributions.
Effect of Repeated Exposure to Alcohol on the Response of the Hypothalamic‐Pituitary‐Adrenal Axis of the Rat: I. Role of Changes in Hypothalamic Neuronal Activity
Authors: Lee Soon , Schmidt E. Donné , Tilders Fred J. H. , Rivier Catherine 
Published: April 2006

Background: Prior (3–12 days) injection of alcohol significantly blunts the response of the hypothalamic‐pituitary‐adrenal (HPA) axis to a second drug challenge without measurably altering responses to other stressors. We therefore determined whether adaptation in hypothalamic neurons underlies this decreased activity.Methods: Adult male rats were administered alcohol (4.5 g/kg intragastrically) or vehicle daily for three consecutive days and then were challenged with the vehicle or alcohol 7 days later. Levels of adrenocorticotropin hormone (ACTH) in the circulation, corticotropin‐releasing factor (CRF), CRF receptors type 1 (CRFR1) and vasopressin (VP) transcripts in the paraventricular nucleus (PVN) of the hypothalamus, and CRF/VP peptide in the median eminence were measured.Results: Resting PVN levels of CRF, CRFR1, and VP were comparable in all animals on day 7 of recovery, whereas CRF and VP stores in the external zone of the median eminence were decreased in animals previously exposed to alcohol. After the acute alcohol challenge on day 7, rats previously exposed to the drug exhibited a significant (p < 0.01) dampening of their PVN CRF and CRFR1, but not VP neuronal response, compared with vehicle‐pretreated rats.Conclusion: Blunted neuronal activity of PVN CRF neurons may be responsible for the decreased ACTH response that we previously reported in rats that had been injected with alcohol several days earlier. In addition, and despite comparable PVN VP transcript levels, the lower levels of this peptide in the median eminence also may participate in the blunted ACTH response that we observed.
Differences in Services Utilization Between White and Mexican American DUI Arrestees
Authors: Cherpitel Cheryl J. 
Published: April 2006

Background: Hispanics traditionally have been considered an underserved population in relation to medical care and related services utilization.Methods: Selected health and social services utilization (both alcohol‐specific and non‐alcohol‐specific) during the last year was compared between a sample of 249 Mexican American (half of whom were born in Mexico) and 250 white participants interviewed in all five DUI (driving under the influence) treatment programs in one northern California county.Results: Among those who met DSM‐IV criteria for alcohol dependence and/or alcohol abuse, 49% of the white subjects compared with 59% of the Mexican American subjects reported no utilization, 77% of whites and 82% of Mexican Americans reported no utilization in which drinking was a factor, and 70% of whites and 80% of Mexican Americans reported no contact with an alcohol program. Mexican Americans were also significantly less likely to report contact with more than one program, and among Mexican Americans, those born in Mexico were significantly less likely to report utilization than those born in the U.S.Conclusions: The data suggest that despite the higher rates of heavy drinking found among Mexican American DUI arrestees (especially those born in Mexico) in this sample, Mexican Americans with an alcohol use disorder are less likely to use health and social services than whites, and this may be related to country of birth and related variables that include health insurance.Significance: The data suggest that DUI programs may offer one of the few opportunities Me‐ican American problem drinkers have of establishing contact with the health and social service system and, as such, would be well positioned to also offer other types of alcohol‐related health and social services and referrals to this underserved population. These findings have implications for intervention efforts for problem drinking and prevention of DUI among Me‐ican Americans, which are a rapidly growing ethnic minority in California.
Long‐Lasting Resistance to Extinction of Response Reinstatement Induced by Ethanol‐Related Stimuli: Role of Genetic Ethanol Preference
Authors: Ciccocioppo Roberto , Angeletti Stefania , Weiss Friedbert 
Published: April 2006

Background: The conditioning of ethanol's reinforcing effects with specific environmental stimuli is thought to be a critical factor in long‐lasting relapse risk associated with alcoholism. To study the significance of such learning factors in the addictive potential of ethanol, this experiment was designed (1) to characterize the effects of stimuli associated with alcohol availability on the reinstatement of responding at a previously ethanol‐paired lever in rats with genetically determined ethanol preference versus nonpreference and (2) to examine the persistence of the motivating effects of these stimuli over time.Methods: Male alcohol‐preferring (P) and alcohol‐nonpreferring (NP) rats were trained to operantly self‐administer ethanol (10% w/v) or water on a fixed‐ratio 1 schedule in a 30‐min daily session. Ethanol and water sessions were scheduled in random sequence across training days. Ethanol availability was signaled by an olfactory discriminative stimulus (banana extract, S+), and each lever press was paired with brief presentation of the conditioning chamber's house light (CS+). The discriminative stimulus signaling water availability (i.e., nonreward) consisted of anise odor (S−), and lever‐responses during water sessions were paired with a brief white noise generation (CS−). The rats then were placed on extinction conditions during which ethanol and water, as well as the corresponding stimuli, were withheld. The effects of noncontingent exposure to the S+ versus S− paired with response‐contingent presentation of the CS+ versus CS− on responding at the previously active lever were then determined in 30‐min reinstatement sessions. To study the resistance to extinction of the effects of the ethanol‐associated stimuli, additional tests were conducted at 3‐day intervals for a total of 50 days.Results: The number of ethanol‐reinforced responses during self‐administration training was significantly greater in P than in NP rats (p < 0.01). After extinction, a significant recovery of responding was observed in both groups of rats under the stimulus conditions associated with ethanol (S+/CS+) but not those associated with water (S−/CS−). However, the response reinstatement was significantly greater in P than NP rats (p < 0.01). In addition, the results revealed a considerable resistance to extinction to the effects of the ethanol‐associated stimuli. Throughout the 50‐day test period, responding remained significantly above extinction levels in both P and NP rats (p < 0.01), but with an overall greater number of responses in P than NP rats (p < 0.05).Conclusions: The results support the hypothesis that conditioning factors contribute importantly to compulsive ethanol seeking and long‐lasting vulnerability to relapse. In addition, the results suggest that genetic predisposition toward heightened ethanol intake extends to greater susceptibility to the motivating effects of ethanol‐related environmental stimuli.
Alcohol Use and Sexual Risk Taking Among Hazardously Drinking Drug Injectors Who Attend Needle Exchange
Authors: Stein Michael D. , Anderson Bradley , Charuvastra Anthony , Friedmann Peter D. 
Published: April 2006

Background: To determine if sex‐risk days are also alcohol use days for active injection drug users.Methods: Cross‐sectional interview of 187 active injection drug users who scored positively (≥8) on the Alcohol Use Disorders Identification Test who were recruited between February 1998 and October 1999 from a needle exchange program in Providence, Rhode Island. A sex‐risk day was defined as “vaginal sex, anal sex or oral sex without a condom,” measured by using a 30 day timeline follow‐back procedure.Results: The sample was 64% male and 87% white, and 85% met DSM‐IV criteria for alcohol abuse/dependence. Of the total days analyzed (n= 5610), 19% were sex‐risk days; on 52% of these days drinking also occurred. By using a generalized estimating equation model to cluster by subject, alcohol use was associated with sex‐risk days (odds ratio, 1.76; 95% confidence interval, 1.35–2.29;p < 0.001), when we controlled for gender, age, race, education, cocaine use, injection frequency, exchanging sex for money or drugs, number of sexual partners, and perceived sexual risk of acquiring human immunodeficiency virus from partners.Conclusions: Alcohol use is associated with sex risk‐taking behavior among injection drug users. A substantial majority of participants reported using alcohol before or during sexual relations, which temporally links alcohol use with human immunodeficiency virus injection risk.
Non‐Transferrin‐Bound Iron in Alcohol Abusers
Authors: de Feo Tullia Maria , Fargion Silvia , Duca Lorena , Cesana Bruno Mario , Boncinelli Lodovico , Lozza Paola , Cappellini Maria Domenica , Fiorelli Gemino 
Published: April 2006

Background: Non‐transferrin‐bound iron, a low‐molecular‐weight iron complex capable of initiating free radical formation and lipid peroxidation, has been detected in the serum of animals experimentally fed with alcohol, but no data have been reported in alcohol abusers. The purpose of this study was to evaluate whether non‐transferrin‐bound iron is present in chronic alcohol abusers with liver involvement and whether alcohol plays any part in its appearance.Methods: We measured non‐transferrin‐bound iron in a cohort of chronic alcohol abusers with and without liver cirrhosis at presentation, when 43 were active abusers and 33 were abstainers, and in a smaller group during a follow‐up period.Results: At presentation, non‐transferrin‐bound iron was detectable in 83.7% of active abusers but only in 21.2% of abstainers, and within the group of abusers, patients with cirrhosis had significantly higher non‐transferrin‐bound iron than patients without. Non‐transferrin‐bound iron was present not only in patients with transferrin saturation >45% but also in those with transferrin saturation ≤45%. Multiple regression analyses revealed that only alcohol intake and total bilirubin were associated independently with non‐transferrin‐bound iron values. Longitudinal study confirmed the data of the cross‐sectional study.Conclusions: Non‐transferrin‐bound iron could have a role in initiating or promoting alcohol‐induced liver damage.
Selective Vulnerability of Embryonic Cell Populations to Ethanol‐Induced Apoptosis: Implications for Alcohol‐Related Birth Defects and Neurodevelopmental Disorder
Authors: Dunty William C. , Chen Shao‐yu , Zucker Robert M. , Dehart Deborah B. , Sulik Kathleen K. 
Published: April 2006

Background: Ethanol‐induced cell death has been characterized in very few stages of embryogenesis. This investigation comprehensively maps patterns of both programmed and ethanol‐induced cell death in the central nervous system and craniofacial region at 0.5‐day intervals from gestational day (GD) 6.5 to 11 in mice.Methods: A teratogenic dosage of ethanol (2.9 g/kg) or vehicle was administered via two intraperitoneal injections to pregnant C57BL/6J mice at various stages of gestation. Cell death patterns were characterized using Nile blue sulfate vital staining and histological analysis of plastic sections. Confocal laser scanning microscopy of LysoTracker Red–stained specimens allowed for three‐dimensional visualization of areas of apoptosis and precise sectional imaging of mouse embryos. Apoptosis was also documented using a TUNEL technique on histological sections.Results: Normal programmed cell death in control embryos was noted in the prechordal plate region at GD 8, the neuroepithelium of the fourth ventricle and anterior neuropore at GD 9, and within the ganglia of cranial nerves V, VII–VIII, IX, and X at GD 10. Acute maternal ethanol administration 12 hr before examination resulted in a dramatic increase in apoptosis within sites of programmed cell death in the embryo. Moreover, ethanol‐exposed specimens exhibited stage‐dependent excessive cell death in other distinct cell populations, particularly within the developing central nervous system. Ethanol‐induced apoptosis was notable as follows: GD 7.5‐neuroectoderm; GD 8‐neural plate and primitive streak; GD 9‐alar plate and presumptive neural crest of the rostral hindbrain, especially at the mesencephalon/rhombencephalon junction; GD 9.5–10‐branchial arches and rhombomeres; and GD 11‐diencephalon, basal ganglia, pons, and developing cerebellum.Conclusions: The results of this study revealed developmental stage‐specific cell populations of the developing brain and craniofacial region that are vulnerable to ethanol‐induced apoptosis and provide new insight relative to the genesis of alcohol‐related birth defects.
Ionotropic Glutamate Receptor Subunit Expression in the Rat Hippocampus: Lack of an Effect of a Long‐Term Ethanol Exposure Paradigm
Authors: Ferreira Vania M. , Frausto Shanti , Browning Michael D. , Savage Daniel D. , Morato Gina S. , Valenzuela C. Fernando 
Published: April 2006

Background: Studies have shown that acute ethanol exposure inhibits ionotropic glutamate receptor function and that long‐term ethanol exposure results in maladaptive increases in the expression of some of these receptors in neurons. It has been postulated that these changes, when unopposed by ethanol, contribute, in part, to the hyperexcitability associated with ethanol withdrawal. In this study, we compared the effect of long‐term ethanol exposure on the hippocampal expression levels of subunits belonging to the three families of ionotropic glutamate receptors.Methods: Adult male Sprague‐Dawley rats were fed an ethanol‐containing diet for 16 days. This diet contained 0% ethanol on days 1 and 2, 3% on days 3 and 4, 5% on days 5 to 7, and 6.7% on days 8 to 16. Control rats received an equivalent amount of an isocaloric diet without ethanol. Rats were killed on day 16 at the peak of ethanol consumption. Hippocampal homogenates were prepared by sonication and analyzed by Western immunoblotting techniques. On a separate group of rats, we measured withdrawal scores and audiogenic seizures on day 17.Results: Ethanol‐exposed rats had significantly higher withdrawal scores, and a significantly higher percentage of them developed audiogenic seizures; this indicates that the 16‐day ethanol diet induces ethanol dependence. Unexpectedly, we found that expression of NR1 (including the expression of NR1 subunits containing the N1, C1, and C2 inserts), NR2A, NR2B, NR2C, GluR1, GluR2/3, GluR5, GluR6/7, and KA2 subunits was not altered in hippocampal homogenates from ethanol‐exposed rats.Conclusions: These results indicate that maladaptive changes in the hippocampal expression levels of ionotropic glutamate receptor subunits do not always occur in ethanol‐dependent rats. Consequently, other mechanisms must mediate the hyperexcitability state associated with ethanol withdrawal in these animals.
Prolonged Hya‐Disparate Skin Graft Survival in Ethanol‐Consuming Mice: Correlation With Impaired Delayed Hypersensitivity
Authors: Wang Kegiang , Busker‐Mannie Ann E. , Hoeft Jennifer , Vasquez Kristine , Miller Stephen D. , Melvold Roger W. , Waltenbaugh Carl 
Published: April 2006

Background: Ethanol consumption impairs cell‐mediated immunity and enhances humoral immunity. Among cell‐mediated immune reactions, little is known of the effect of ethanol on chronic graft rejection. Allograft responses against the male‐specific minor histocompatibility antigen, Hya, are widely used to study chronic graft rejection.Methods: Female C57BL/6 (B6) mice were fed ethanol‐containing liquid diets, were pair‐fed an isocaloric liquid control diet, or were fed solid diet and water ad libitum. One week after diet initiation, the mice were grafted with split thickness, orthotopic male tail skin grafts, and the integrity of the grafts was monitored as the diet continued. Delayed hypersensitivity (DTH) was also determined in these same mice. In addition, Hya‐cytolytic T‐cell–deficient syngeneic major histocompatibility complex mutant B6.C‐H2bm13 (bm13) and B6.C‐H2bm14 (bm14) mice were assessed for skin graft rejection, DTH, and cytotoxic T‐lymphocyte (CTL) activity.Results: Ethanol‐consuming female B6 mice are impaired in their ability to reject syngeneic male skin grafts and to develop Hya‐specific DTH responses. To address the underlying mechanism, we show that Hya graft rejection correlates with DTH and not with CTL activity. Female B6 mice clearly differ from female bm13 and bm14 mice in their ability to generate CTLs against Hya antigen. Despite their inability to make Hya‐specific CTL responses, bm13 and bm14 female mice, nevertheless, make Hya‐specific DTH responses and ultimately reject Hya‐disparate skin grafts, indicating that Hya‐specific graft rejection results from DTH. Ethanol, by impairing Hya‐specific DTH, inhibits Hya‐specific skin graft rejection.Conclusions: We demonstrate that ethanol consumption impairs Hya‐specific graft rejection. In addition, experiments with mice unable to generate anti‐Hya CTLs support previous observations suggesting that DTH responses are sufficient to cause rejection of Hya‐incompatible grafts.
Effects of Naltrexone and Ro 15‐4513 on a Multiple Schedule of Ethanol and Tang Self‐Administration
Authors: Shelton Keith L. , Grant Kathleen A. 
Published: April 2006

Background: Both the opioid antagonist, naltrexone, and GABAA/benzodiazepine‐site negative modulator, Ro 15‐4513, decrease ethanol self‐administration in rodents and nonhuman primates. However, the selectivity of these drugs for decreasing ethanol self‐administration relative to reducing responding maintained by other reinforcers in primates is not clear. The present study used a multiple schedule self‐administration procedure in cynomolgus monkeys to examine the selectivity of naltrexone and Ro 15‐4513 for reducing ethanol self‐administration relative to an orange flavored sugar‐free sweetened solution (Sugar‐free Tang).Methods: Six adult cynomolgus monkeys were trained to self‐administer 4% (w/v) ethanol and 4% or 6% (w/v) Tang under a multiple schedule of liquid access. The effect of acute administration of naltrexone (0.1, 0.3, 1, 3 mg/kg) was examined. The effect of 15 days of chronic, 1 mg/kg naltrexone on ethanol and Tang self‐administration was then examined in four monkeys. Acute administration of Ro 15‐4513 (0.01, 0.03, 0.1, 0.3 mg/kg) as well as 15 days of chronic administration of 0.1 mg/kg Ro 15‐4513 was also examined in four monkeys.Results: Ethanol and Tang were self‐administered at similar volumes and patterns under baseline conditions. Acute naltrexone administration significantly decreased total session ethanol and Tang intake as well as the number and volume of ethanol and Tang drinks. Chronic naltrexone also significantly decreased ethanol and Tang intake. Ethanol, but not Tang, drink volume was significantly decreased by chronic 1 mg/kg naltrexone pretreatment. The number of ethanol and Tang drinks and drink duration were not significantly decreased by chronic naltrexone. Acute Ro 15‐4513 pretreatment significantly decreased ethanol and Tang intake, mean drinks and median drink duration. Chronic 0.1 mg/kg Ro 15‐4513 pretreatment significantly decreased total ethanol intake only during the first week of pretreatment, but it significantly decreased Tang intake for all 3 pretreatment weeks.Conclusions: Similar to rodent studies, acute and chronic naltrexone and Ro 15‐4513 reduced ethanol and Tang intake in cynomolgus monkeys. However, unlike rodent studies, neither drug showed selectivity for reducing ethanol intake compared with a comparison reinforcer. These differences highlight the need for testing putative ethanol abuse treatment drugs under diverse conditions and multiple species before undertaking human clinical trials.
A 2‐Year Follow‐Up of 120 Swedish Female Alcoholics Treated Early in Their Drinking Career: Prediction of Drinking Outcome
Authors: Haver Brit , Dahlgren Lena , Willander Anders 
Published: April 2006

Background: One hundred twenty women alcoholics recruited to a treatment program called EWA (Early Treatment for Women With Alcohol Addiction) were studied. The selected women were not previously treated for alcohol abuse.Methods: The women were followed up by use of a structured personal interview, biomarkers sensitive for alcohol abuse (i.e., glutamyl transpeptidase), and questionnaires, by using defined criteria for abstinence, social drinking, satisfactory drinking outcome, and unsatisfactory drinking outcome.Results: Drinking outcome was good (i.e., total abstinence, social drinking, or satisfactory drinking outcome) for 67% of the women during the total follow‐up time, by use of strict criteria for relapse. The results were corroborated by the biomarkers. Similar results were reported from two previously studied groups of women from the same department. However, the frequency of abstinence was higher and social drinking was significantly lower among this sample of women. Daily drinking, the use of sedatives, and a long duration of pretreatment alcohol abuse predicted an unfavorable outcome. However, a long duration of outpatient treatment predicted a good outcome, whereas treatment dropout was related to an unsatisfactory drinking outcome. A majority of the women (96%) rated the treatment experience and the treatment program favorably. The overall good results might reflect the selection of the subjects studied.Conclusions: Improving treatment program adherence would probably improve outcome for the women with an unsatisfactory drinking outcome.