bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alcohol‐Induced Modulation of the Insulin‐Like Growth Factor System in Early Chick Embryo Cranial Tissue
Authors: A Lynch Steven , Elton C. W. , Melinda Carver F. , Pennington Sam N. 
Published: April 2006

Background: Fetal alcohol exposure has been shown to reduce fetal/embryonic growth. The insulin‐like growth factor (IGF) system plays a major role in normal growth and development of the embryo. The purpose of this study was to gain a better understanding of the effects of alcohol (ethanol, EtOH) exposure on the insulin‐like growth factors, their binding proteins, and receptors during embryonic development.Methods: After the administration of either alcohol or chick Ringer's solution to individual eggs at the start of incubation, type‐1 IGF receptors, IGF‐binding proteins (IGFBPs) as well as IGF‐1 and IGF‐2 levels were measured in chick embryo craniums on days 5, 6, 7, and 8 of incubation.Results: Levels of the IGF‐1 receptor protein were not significantly different between treatment groups on any day studied. In EtOH‐treated embryos, the 30 kDa IGFBP levels were significantly higher than vehicle levels on days 5 and 6. On day 6, IGF‐1 levels were significantly lower in the alcohol‐treated embryos compared with levels in vehicle‐treated embryos of the same age. By day 8 of incubation, IGF‐1 levels were significantly higher and the 30 kDa IGFBP levels were significantly lower in the alcohol‐treated group compared with vehicles. These results indicate an initial EtOH‐associated reduction in the amount of IGF‐1 available to bind to its receptor (bioavailability), followed by increased IGF‐1 bioavailability by day 8.Conclusions: The elevated IGFBP levels and reduced IGF‐1 levels on days 5 and 6 of incubation are congruent with an overall reduction in the bioavailability of IGF‐1 during this period and correlate with the decreased embryo weight observed in the alcohol‐treated embryos. An increased bioavailability of IGF‐1 observed by day 8 may represent a rebound effect and is associated with increases in ornithine decarboxylase activity, a marker of increased growth.
Fetal Alcohol Exposure and Temporal Vulnerability: Effects of Binge‐Like Alcohol Exposure on the Ventrolateral Nucleus of the Thalamus
Authors: Livy D. J. , Maier Susan E. , West James R. 
Published: April 2006

Background: Prenatal alcohol exposure disrupts motor performance in affected offspring. The ventrolateral nucleus (VLN) of the thalamus functions to relay information between the cerebellum and motor cortex. Reductions in the size of the thalamus have been found in children with fetal alcohol syndrome, and therefore a rat model system was used to determine whether VLN size and neuronal number were altered by alcohol exposure during development.Methods: Rat pups were exposed to alcohol in utero during the first 10 days of gestation (first trimester equivalent), the second 10 days of gestation (second trimester equivalent), or the first two trimesters equivalent combined. Some pups were exposed to alcohol in utero during the time of VLN neurogenesis. In addition, offspring from some of the dams treated during the first two trimesters equivalent were reared artificially from postnatal day (P) 4 through P9 (part of the third trimester equivalent) and received binge‐like alcohol during this time, resulting in offspring exposed to alcohol during all three trimesters equivalent. Other offspring from untreated dams were reared in the same manner but received alcohol only during the third trimester equivalent. Control animals (nutritional and untreated) were reared for all treatment conditions. All pups were perfused on P10.Results: A unique effect of alcohol treatment was not found for the VLN volume or the number of neural cells within the VLN. However, the period of VLN neurogenesis was found to be sensitive to both alcohol and nutritional control treatments, resulting in significant decreases in the VLN volume and neural cell number.Conclusions: Motor deficits seen in offspring exposed prenatally to alcohol do not seem to result from direct effects on the structure of the VLN of the thalamus.
Free‐Choice Alcohol Consumption in Mice After Application of the Appetite Regulating Peptide Leptin
Authors: Kiefer F. , Jahn H. , Wolf K. , Kämpf P. , Knaudt K. , Wiedemann K. 
Published: April 2006

Background: Leptin has been shown to regulate food intake and energy expenditure. Very recently, associations of elevated leptin plasma levels during alcohol withdrawal with alcohol craving have been observed in humans. Therefore, we tested the hypothesis that the application of exogenous leptin modulates voluntary alcohol consumption in mice.Methods: Sixteen mice (129/Sv x C57BL/6J) were habituated to ethanol consumption over a time period of 3 months. After a basal 2‐week free‐choice drinking phase, mice were separated into two groups (n= 8) according to weight and alcohol consumption. They received recombinant leptin (1 mg/kg) versus saline intraperitoneally daily for 10 days. After 4 days of free‐choice consumption of ethanol (16% v/v) versus water, ethanol was withdrawn at day 4 and replaced at day 6 to test the occurrence of an alcohol deprivation effects. Fluid intake was evaluated by controlling the weight of the drinking tubes daily.Results: Free‐choice ethanol consumption after withdrawal was significantly elevated in mice after intraperitoneal injection of 1 mg/kg leptin (alcohol deprivation effect), but not during basal drinking.Conclusion: We suggest that leptin may enhance motivation for alcohol consumption in habituated mice after alcohol withdrawal.
Genetic Repeat Polymorphism in the Regulating Region of CYP2E1: Frequency and Relationship With Enzymatic Activity in Alcoholics
Authors: Plee‐Gautier E. , Foresto F. , Ferrara R. , Bodénez P. , Simon B. , Manno M. , Berthou F. , Lucas D. 
Published: April 2006

Background: Differences in the regulatory region of the CYP2E1 gene could be responsible for the interindividual variation in the cytochrome P‐450 2E1 (CYP2E1) involved in ethanol oxidation. Recently, a polymorphic repeat sequence in the human gene was described between −2178 and −1945 base pairs. Its frequency seemed to vary among different ethnic populations, and it was suspected to be related to an increased inducibility to further ethanol intake. In the study reported here, the frequency of this polymorphism was investigated in a white French population. Its relationship with the previously described Pst I/Rsa I or Dra I CYP2E1 polymorphisms, alcoholism, alcoholic liver disease, and inducibility of CYP2E1 by ethanol was examined.Methods: The polymorphic region was characterized by polymerase chain reaction in 103 controls, 148 alcoholic subjects without liver diseases, and 98 others with liver cirrhosis. By using in vivo chlorzoxazone (CHZ) metabolism, CYP2E1 phenotype was assessed in 36 non–ethanol‐induced subjects (17 controls and 19 withdrawn alcoholics) and in 14 ethanol‐induced subjects (10 controls after ingestion of 0.8 g/kg ethanol and four alcoholics with 100 g of daily intake). This phenotype was expressed as the 6‐hydroxy CHZ/CHZ ratio.Results: The rare allele frequency was found to be 1.58% in whites (n= 349). Neither significant association with alcoholism or alcoholic liver diseases, nor relationship with the Pst I/Rsa I polymorphism, was observed. But the Dra I polymorphism was more frequent among the heterozygous subjects when compared with wild‐type homozygous ones (p < 0.05). The CYP2E1 phenotype was similar in wild‐type homozygotes and in heterozygotes at the constitutive level, as well as after induction with ethanol.Conclusions: Our data suggest that CYP2E1 repeat polymorphism does not seem to constitute a major factor for interindividual differences in CYP2E1 expression and susceptibility to alcohol‐related disorders in whites.
No Association Between the Dopamine D2 Receptor Taq I A1 Allele and Earlier Age of Onset of Alcohol Dependence According to Different Specified Criteria
Authors: Anghelescu Ion , Germeyer Sabine , Müller Matthias J. , Klawe Christoph , Singer Peter , Dahmen Norbert , Wetzel Hermann , Himmerich Hubertus , Szegedi Armin 
Published: April 2006

Background: The presence of the A1 allele of the dopamine D2 receptor Taq I restriction fragment length polymorphism has been reported to be associated with an earlier age of onset of alcohol dependence as a marker for severity.Methods: We tested this hypothesis with special regard to the definition of the age of onset of alcoholism in 243 patients with alcohol dependence, according to DSM‐IV criteria assessed by the standardized interview Münchner Composite International Diagnostic Interview (M‐CIDI), consecutively admitted for detoxification. Additionally, the Addiction Severity Index (ASI) was performed. The Taq IA polymorphism was amplified by polymerase chain reaction (PCR), and the PCR product was digested by the restriction enzyme Taq I. Patients were subsequently divided into an A1 (presence of at least one A1 allele, n= 88) and an A2 group (absence of an A1 allele, n= 155). The following criteria for different definitions of age of onset were used: (1) age of onset of the first occurring symptom necessary for the diagnosis of alcohol dependence according to M‐CIDI; (2) age of onset of the last symptom of alcohol dependence according to M‐CIDI; (3) age of onset of more than 3 drinking days per week on a regular basis according to ASI; (4) age of onset of more than 3 drinking days—of more than five drinks per drinking day—or at least one binge drinking episode per week on a regular basis according to ASI.Results: The frequency of the A1 allele in our patient sample was 0.208. No statistically significant association between the A1 allele and the age of onset of alcoholism was found. The mean age of onset according to criterion 1 was 30.4 ± 10.8 years for the A1 group and 30.2 ± 10.2 years for the A2 group (p= 0.89); for criterion 2, it was 33.3 ± 10.0 years for the A1 group and 33.9 ± 10.2 years for the A2 group (p= 0.77); for criterion 3, it was 18.0 ± 7.5 years for the A1 group and 18.1 ± 6.1 years for the A2 group (p= 0.92); and for criterion 4, it was 22.3 ± 9.7 years for the A1 group and 21.8 ± 8.5 years for the A2 group (p= 0.76).Conclusions: No association was found between the A1 polymorphism and age at onset of alcohol dependence according to different specified criteria.
Family Interactions of Alcoholics as Related to Alcoholism Type and Drinking Condition
Authors: Jacob Theodore , Leonard Kenneth E. , Randolph Haber Jon 
Published: April 2006

Background: Several studies have reported that the marital interactions of antisocial and aggressive, versus nonantisocial and nonaggressive, alcoholics exhibit higher rates of aversive‐defensive communications and higher levels of negative reciprocity. To extend these findings, we examined the effect of alcoholism type (high‐ versus low‐antisocial alcoholics: HAS, LAS) and drinking condition on family communication patterns.Methods: Marital and parent‐child dyads from 100 alcoholic families were videotaped while they discussed personally relevant issues during drinking and no‐drinking sessions (no children were offered any alcohol). All interactions were coded with the Marital Interaction Coding System, and the data were assessed for differences in rate of positive, negative, and problem‐solving behaviors, as well as sequential structures.Results: HAS couples were more negative during the drink versus no‐drink condition, whereas drinking did not affect negativity for LAS couples. In addition, the negative communications of HAS versus LAS alcoholics were more likely to increase spouse negativity during the drink versus no‐drink condition. Group differences for parent‐child interactions were few.Conclusions: The nature of family interactions was related to both alcoholism type and alcohol consumption, and the marital interactions of alcoholism types could be differentiated on the basis of the frequency and sequential structure of negative exchanges. It is most important to note that it is the interactions of the HAS alcoholic that undergo the most change as a function of drinking condition, with little support for the “adaptive consequences” hypothesis that alcohol consumption leads to more effective problem‐solving for couples in which the alcoholic exhibits fewer antisocial and more internalizing characteristics. Study limitations and directions for future research are discussed.
Effects of Assessment Frequency on Subjective Intoxication Ratings After Alcohol Consumption
Authors: Sayette Michael A. , Martin Christopher S. , Perrott Michael A. 
Published: April 2006

Background: It is common for subjective intoxication measures to be administered frequently throughout an experimental session. It is unclear, however, whether repeated assessments affect the experience of intoxication. This study examined the effect of assessing subjective intoxication levels during alcohol consumption on subsequent perceptions of intoxication after drinking.Methods: Forty‐two participants consumed a moderate dose of alcohol (men, 82 g/kg; women, 0.74 g/kg) during a 30‐min period. Participants either reported or did not report subjective intoxication levels at 10‐min intervals during the drinking period. After the drink, all participants rated their level of subjective intoxication on several occasions.Results: Individuals who reported their intoxication during the drinking period reported higher levels after consumption than did those who did not rate their intoxication during drinking.Conclusions: These data suggest the potential for reactivity effects when conducting repeated assessments of perceived subjective intoxication.
Variations in Corticosterone Feedback Do Not Reveal Differences in HPA Activity After Prenatal Ethanol Exposure
Authors: Gabriel Kara I. , Ellis Linda , Yu Wayne , Weinberg Joanne 
Published: April 2006

Background: Prenatal ethanol exposure results in hypothalamic‐pituitary‐adrenal (HPA) hyperresponsiveness to stressors in adult animals. Possible mechanisms mediating this alteration in HPA responsiveness include stress‐associated changes in corticosterone (CORT) feedback signals, alterations in CORT signals under basal conditions, and CORT‐independent mechanisms.Methods: We examined the effects of adrenalectomy (ADX) and CORT replacement with a constant, low‐level CORT signal via CORT/cholesterol pellets on HPA responses to restraint stress. Adult Sprague‐Dawley rats from prenatal ethanol (E), pair‐fed (PF), and ad libitum–fed control (C) groups underwent sham ADX (sham), ADX without CORT replacement, or ADX with CORT replacement. Animals were tested during the trough of the circadian rhythm.Results: In the sham condition, E females showed increased adrenocorticotropin hormone (ACTH) and CORT responses to restraint stress compared with C females. Basal and stress‐induced ACTH levels were significantly increased in ADX compared with sham animals across all prenatal groups. Constant CORT replacement reduced basal ACTH levels compared with levels in the ADX group, although levels were still increased compared with those observed in the sham group. CORT replacement was minimally effective at reducing ACTH levels during stress.Conclusions: Although the effects of ADX may have masked possible influences of circadian drive or prenatal group, these findings suggest that in the absence of a CORT feedback signal or in the presence of a constant, low‐level CORT feedback signal, E, PF, and C animals do not differ in their abilities to regulate ACTH secretion during the trough of the circadian rhythm.
Effects of Ethanol and Naltrexone in a Model of Traumatic Brain Injury With Hemorrhagic Shock
Authors: Zink Brian J. , Schultz Carol H. , Stern Susan A. , Mertz Michelle , Wang Xu , Johnston Peter , Keep Richard F. 
Published: April 2006

Background: Ethanol predisposes to traumatic injury and causes respiratory depression and cardiovascular compromise in models of traumatic brain injury (TBI) and hemorrhagic shock (HS). Endogenous opioids may play a role in ethanol intoxication and TBI. We studied the effects of ethanol and the opiate antagonist agent naltrexone (NTX) in a TBI/HS model.Methods: Fifty‐six pigs (20 kg) were anesthetized with isoflurane, intubated, instrumented, and subjected to fluid percussion TBI with concurrent 30 ml/kg hemorrhage over 30 min. Seven groups were studied: Control, EtOH, NTX, INJ, INJ/EtOH, INJ/NTX, and INJ/EtOH/NTX. Ethanol (2 g/kg IV) was given preinjury, followed by infusion of 0.4 g/kg/hr. NTX 0.3 mg/kg intravenous was given 5 min postinjury. Parameters monitored for 120 min postinjury included minute ventilation (VE), blood pressure (MAP), cerebral perfusion pressure (CPP), cerebral venous lactate (Lac), arterial and cerebral venous blood gases, and brain tissue PtiO2.Results: Ethanol levels at injury were 220 mg/dL. Ethanol‐treated animals had depression of hypercapnic ventilatory response, which was reversed by administration of naltrexone. MAP and CPP were significantly lower in injured animals, but were not significantly improved by NTX. Cerebral venous pH was lower and lactate was higher in ethanol‐treated animals.Conclusion: In this TBI/HS model, NTX reverses ethanol‐induced depression of hypercapnic ventilatory response but does not improve MAP, CPP, or metabolic acidosis. This suggests that the respiratory effects of ethanol in TBI, but not the hemodynamic effects, may be mediated by opiate receptor activation.
Chemical Pathology in Brain White Matter of Recently Detoxified Alcoholics: A 1H Magnetic Resonance Spectroscopy Investigation of Alcohol‐Associated Frontal Lobe Injury
Authors: Schweinsburg Brian C. , Taylor Michael J. , Alhassoon Omar M. , Videen John S. , Brown Gregory G. , Patterson Thomas L. , Berger Fred , Grant Igor 
Published: April 2006

Background: Investigations have suggested that frontal lobe abnormalities are a prominent feature of the alcoholic brain, indicated by impaired neuropsychological performance on tests of frontal lobe function and by reduced frontal lobe volume in neuroimaging and neuropathological examinations. White matter compartment volume loss may underlie observed brain shrinkage and cognitive deficits associated with the frontal lobes, although the nature of this change has not been well‐characterized.Method: To investigate the susceptibility of frontal lobe white matter to alcohol‐associated metabolic change and to understand the nature of alcohol‐related white matter injury, 1H magnetic resonance spectroscopy (MRS) was used to measure concentrations of metabolites in frontal white matter (FWM) and parietal white matter (PWM) of recently detoxified alcoholics (RDA) and nonalcoholic controls (CON). Concentrations of N‐acetylaspartate (NAA), choline‐containing compounds (Cho), myo‐inositol (Ins), and creatine plus phosphocreatine (Cr) were measured in 37 RDA (mean age, 40.4 years; mean length of abstinence, 27.9 days) and 15 CON (mean age, 38.0 years).Results: Analysis of variance (ANOVA) revealed a group by region of interest interaction for concentrations of NAA. Simple effects analysis revealed a significant 14.7% reduction in FWM NAA, while NAA levels in PWM were similar in RDA and CON. In addition, RDA had an 11.8% increase (averaged across both regions of interest) in brain white matter Ins relative to CON. Reductions in FWM NAA were associated with a longer drinking history in the RDA group, but this result was not found when both age and drinking history were used to predict the level of FWM NAA.Conclusions: Alcohol‐associated reductions in FWM NAA may be the result of neuronal loss or dysfunction in the metabolism of NAA. While alcohol‐induced oxidative stress may cause global brain impairments in the metabolism and subsequent reduction of NAA, the frontal lobes are particularly rich in excitatory amino acid pathways, and axonal damage or destruction secondary to glutamate‐mediated excitotoxicity during alcohol withdrawal may cause frontal lobe‐specific reductions in NAA. Elevations in brain white matter Ins may reflect astrocyte proliferation as well as an osmotic response to cell shrinkage.
Inhibition of Caspases In Vivo Protects the Rat Liver Against Alcohol‐Induced Sensitization to Bacterial Lipopolysaccharide
Authors: Deaciuc Ion V. , D'souza Nympha B. , de Villiers Willem J. S. , Burikhanov Ravshan , Sarphie Theodore G. , Hill Daniell B. , McClain Craig J. 
Published: April 2006

Background: The mechanisms of liver sensitization by alcohol to Gram‐negative bacterial lipopolysaccharide (LPS) remain elusive. The purpose of this study was two‐fold: (1) to test the hypothesis that alcohol‐enhanced liver apoptosis may be a sensitizing mechanism for LPS and (2) to further characterize the liver apoptotic response to alcohol.Methods: Rats were fed a high‐fat, alcohol‐containing liquid diet for 14 weeks, treated with LPS (1.0 mg/kg of body weight, intravenously) or saline, followed by injection of a pan‐caspase inhibitor {IDN1965;N‐[(1,3‐dimethylindole‐2‐carbonyl)‐valinyl]‐3‐amino‐4‐oxo‐5‐fluoropentanoic acid; 10 mg/kg of body weight, intraperitoneally} or vehicle, and killed. The following parameters were assessed: plasma aspartate: 2‐oxoglutarate aminotransferase activity (AST); liver histology and terminal deoxyribonucleotidyl transferase‐mediated dUTP nick end labeling (TUNEL) response; caspase‐3, −8, and −9 activity; and mRNA and protein expression for two apoptosis‐signaling molecules: Fas receptor and Fas ligand; and three apoptosis adaptors: Bax, Bcl‐XL, and Bcl‐2.Results: Alcohol‐feeding‐induced liver steatosis, slightly increased caspases’ activity, the number of TUNEL‐positive nuclei, and facilitated the LPS necrotic effect without affecting mRNA expression of apoptosis signals and adaptors. LPS induced a significant increase in AST and the number of TUNEL‐positive nuclei, both effects being more pronounced in alcohol‐treated rats. LPS produced hepatic necrosis only in alcohol‐treated rats. LPS effects were associated with up‐regulation of mRNA expression for both apoptosis adaptors and signaling molecules. IDN1965 administration 3 hr after LPS injection strongly inhibited caspases’ activity, particularly that of caspase‐3. IDN1965 also abolished the increase in TUNEL‐positive nuclei, reversed the effect of LPS on plasma AST in alcohol‐treated rats, and prevented LPS‐induced necrosis.Conclusions: (1) Alcohol‐enhanced liver apoptosis may not involve regulatory steps at the transcriptional level. LPS‐induced liver apoptosis seems to involve transcriptional regulation of several apoptosis adaptors. Therefore, alcohol and LPS may enhance liver apoptosis through different mechanisms. (2) Alcohol‐enhanced liver apoptosis precedes and may facilitate the hepatic effects of LPS. LPS superimposed on alcohol further elevates the rate of apoptosis in the liver. This may exceed the phagocytosing capacity of the liver so that all the apoptotic cells are not phagocytosed, but rather die of necrosis.