bluuebunny/crossref_metadata_2025_split huggingface dataset:
Naltrexone Depot for Treatment of Alcohol Dependence: A Multicenter, Randomized, Placebo‐Controlled Clinical Trial
Authors: Kranzler Henry R. , Wesson Donald R. , Billot Laurent ,   DrugAbuse Sciences Naltrexone Depot Study Group
Published: July 2004

Background: Studies of the efficacy of naltrexone for alcohol dependence have yielded variable findings, which may be due, in part, to variation in compliance with oral naltrexone. Efforts to improve naltrexone compliance have included the development of injectable, long‐acting depot formulations.Methods: We conducted a multicenter trial in 315 subjects who were randomly assigned to receive an intramuscular injection of a depot formulation containing naltrexone (n= 158) or a placebo formulation (n= 157) monthly for 3 months. All patients received five sessions of manual‐guided motivational enhancement therapy during the 12 weeks of the study. The outcomes of interest were based on self‐reported alcohol use and γ‐glutamyl transpeptidase level. Missing data or data from subjects who discontinued the study were conservatively treated as heavy‐drinking days.Results: Groups were comparable on pretreatment demographic and clinical measures. The medication was well tolerated; 73.7% of subjects received all injections. The time to the first heavy‐drinking day, the percentage of subjects with no heavy drinking throughout the study, and γ‐glutamyl transpeptidase levels favored the naltrexone depot, although the effects did not reach statistical significance. There was a significant advantage for naltrexone depot treatment on the time to the first drinking day. Naltrexone depot subjects also had significantly fewer drinking days during treatment and a significantly greater abstinence rate than the placebo group (18% vs. 10%).Conclusions: This is the first multicenter study of a depot formulation of naltrexone for the treatment of alcohol dependence. Using a conservative intent‐to‐treat analysis, the study showed an advantage for the active medication. Further research with this formulation is warranted.
Desensitization of PKA‐Stimulated Ciliary Beat Frequency in an Ethanol‐Fed Rat Model of Cigarette Smoke Exposure
Authors: Wyatt Todd A. , Gentry‐Nielsen Martha J. , Pavlik Jacqueline A. , Sisson Joseph H. 
Published: July 2004

Background: Our previous studies have shown that the ciliary beat frequency (CBF) of cultured ciliated airway epithelial cells exposed to chronic ethanol fails to increase in response to β‐agonist stimulation. This loss of the ciliary “flight response” correlates with an ethanol‐mediated desensitization of adenosine 3′:5′‐cyclic monophosphate‐dependent protein kinase (PKA), a known regulatory component of CBF stimulation. We hypothesized that a similar ethanol‐mediated desensitization of CBF would occur in vivo.Methods: Sprague Dawley® rats were fed a liquid diet containing various concentrations of ethanol for 1 or 5 weeks. Half were exposed to cigarette smoke for 12 weeks and half were sham exposed. Animals were killed and tracheal epithelial cells analyzed for CBF and PKA activity.Results: Baseline CBF (∼6Hz) was unchanged in tracheal epithelial cells of rats consuming diets containing 0–36% ethanol for 5 weeks. Isoproterenol stimulated CBF to 12 to 13 Hz in the tracheal epithelial cells of control rats not administered ethanol. However, isoproterenol stimulation of CBF was blunted to 7.5 Hz in rats eating a 26% ethanol diet, and there was no stimulation of CBF in rats fed a diet containing 36% ethanol. Similarly, isoproterenol stimulated a 2‐ to 3‐fold increase in PKA activity in control rats, but this PKA response to isoproterenol was blunted in rats fed increasing concentrations of ethanol. No isoproterenol‐stimulated PKA response was observed in rats fed 36% ethanol. No ethanol‐induced changes in cyclic guanosine monophosphate‐dependent protein kinase or protein kinase C were observed in the rats’ tracheal epithelial cells. Cigarette smoke exposure slightly elevated baseline CBF and lowered the ethanol consumption level for isoproterenol‐desensitization of CBF and PKA activation to 16%. No isoproterenol desensitization was observed after 1 week of alcohol feeding. Furthermore, 36% ethanol‐feeding for 1 week stimulated rat tracheal CBF and PKA.Conclusion: These data demonstrate that in vivo administration of ethanol to rats results in decreased ciliary beating and the desensitization of PKA. This suggests a mechanism for mucociliary clearance dysfunction in alcoholics.
Using Daily Interactive Voice Response Technology to Measure Drinking and Related Behaviors in a Pharmacotherapy Study
Authors: Kranzler Henry R. , Abu‐Hasaballah Khamis , Tennen Howard , Feinn Richard , Young Kevin 
Published: July 2004

Background: Interactive voice response technology (IVR) allows investigators to collect daily measures of drinking, medication adherence, mood, and other treatment‐relevant variables that may change day to day during a clinical trial. Despite these advantages, no published studies have used IVR in alcohol pharmacotherapy trials.Methods: Subjects provided daily data via IVR during the 12‐week treatment period. Seven subjects completed the trial.Results: We found a high level of participant adherence to the IVR protocol, higher levels of drinking reported by IVR than by a commonly used recall method, and distinct within‐day associations between daily mood and alcohol consumption: these could not be obtained through traditional assessment methods.Conclusions: IVR seems to be feasible for the collection of daily indicators of treatment outcomes and processes in pharmacotherapy studies among problem drinkers.
Adipogenic Effect of Alcohol on Human Bone Marrow‐Derived Mesenchymal Stem Cells
Authors: Wezeman Frederick H. , Gong Zhaodi 
Published: July 2004

Background: In addition to a decrease in bone mass in alcoholics their osteopenic skeletons show an increase in bone marrow adiposity. Human bone marrow mesenchymal stem cells (hMSC) in vivo differentiate into several phenotypes including osteogenic and adipogenic cells, both of which remain as resident populations of bone marrow. In vitro, the lineage commitment and differentiation of hMSC toward the adipogenic pathway can be promoted by alcohol.Methods: Human male and female mesenchymal stem cells from joint replacement surgery were cultured. Cells were grouped as: 1) Control (no additions to the culture medium), 2) EtOH (50 mm alcohol added to the culture medium), 3) OS (osteogenic inducers added to the culture medium), and 4) OS + EtOH (osteogenic inducers and 50 mm alcohol added to the culture medium). Cultures stained with Nile Red confirmed the development of differentiated adipocytes. Population analysis was performed using fluorescence‐activated cell sorting. Gene expression of early, middle, late, and terminal differentiation stage markers (PPAR)γ2, lipoprotein lipase, adipsin, leptin, and adipocyte P2 (aP2)] was studied by Northern hybridization, and protein synthesis of aP2 was determined by Western analysis.Results: Nile red staining confirmed increased adipocyte development 10 days after the onset of treatment with 50 mm alcohol and osteogenic induction. By day 21 the number of adipocytes increased to 13.6% of the total population. Alcohol up‐regulated the gene expression of PPARγ2 whereas no up‐regulation was observed for the other genes. Protein production of aP2 was significantly increased in hMSC cells by culture in the presence of alcohol.Conclusions: The data suggest that alcohol's adipogenic effect on cultured hMSC is through up‐regulation of PPARγ2 at the point of lineage commitment as well as through enhancement of lipid transport and storage through increased aP2 synthesis. The alcohol‐induced expression and synthesis changes account for the increased Nile red staining of cultured hMSC.
Dose‐Dependent Activation of Ca2+‐Activated K+ Channels by Ethanol Contributes to Improved Endothelial Cell Functions
Authors: Kuhlmann Christoph R. W. , Li Fang , Lüdders Dörte W. , Schaefer Christian A. , Most Astrid K. , Backenköhler Ulrich , Neumann Thomas , Tillmanns Harald , Waldecker Bernd , Erdogan Ali , Wiecha Johannes 
Published: July 2004

Background: Regular moderate alcohol (EtOH) intake seems to protect against both coronary artery disease and ischemic stroke, whereas the risk increases with heavy EtOH consumption. Effects of EtOH on endothelial cell function may be relevant to these disparate effects. Potassium channels play an important role in the regulation of endothelial cell functions. Therefore, we investigated whether Ca2+‐activated K+ channels (BKCa) are modulated by EtOH. Furthermore, we examined whether EtOH‐induced changes of endothelial nitric oxide (NO) formation and cell proliferation are due to BKCa activation.Methods: The patch‐clamp technique was used to investigate BKCa activity in cultured human umbilical vein endothelial cells (HUVEC). NO formation was analyzed by using the fluorescence dye 4,5‐diaminofluorescein. Endothelial proliferation was examined by using cell counts and measuring [3H]thymidine incorporation.Results: EtOH dose‐dependently (10–150 mmol/liter) modulated BKCa‐activity, with the highest increase of open‐state probability at a concentration of 50 mmol/liter (n= 13; p < 0.05). Inside‐out recordings revealed that this effect was due to direct BKCa activation, whereas open‐state probability was not changed in cell‐attached recordings after pertussis toxin preincubation. EtOH (10 and 50 mmol/liter) caused a significant increase of NO levels, which was blocked by the highly selective BKCa inhibitor iberiotoxin (100 nmol/l; n= 30; p < 0.05). Higher concentrations of EtOH (100 and 150 mmol/liter) significantly reduced NO synthesis (n= 30; p < 0.05). Both methods revealed a significant increase of HUVEC proliferation, which was inhibited by iberiotoxin (n= 30; p < 0.05). At a concentration of 150 mmol/liter, EtOH caused a significant reduction of endothelial proliferation.Conclusions: EtOH directly activates BKCa in HUVEC, leading to an increase of endothelial proliferation and production of NO. These results indicate a possible beneficial effect of low‐dose EtOH on endothelial function, whereas higher concentrations must be considered as harmful.
Early Experience and Sex Interact to Influence Limbic‐Hypothalamic‐Pituitary‐Adrenal‐Axis Function After Acute Alcohol Administration in Rhesus Macaques (Macaca mulatta)
Authors: Barr C S. , Newman T K. , Lindell S , Becker M L. , Shannon C , Champoux M , Suomi S J. , Higley J D. 
Published: July 2004

Background: Studies in rodents demonstrate sex differences in neuroendocrine stress axis activity after treatment with alcohol. In abstinent alcoholics, atypical depressives, and individuals with posttraumatic stress disorder, limbic‐hypothalamic‐pituitary‐adrenal (LHPA)‐axis activity is often blunted; among females in these patient populations, however, resistance to glucocorticoid feedback and increased pituitary reactivity is observed. Early parental loss is a major life stressor and is a risk factor for both affective disturbances and LHPA‐axis abnormalities later in life. We wanted to determine whether sex and early life parental absence would interact to influence alcohol‐induced alterations in LHPA‐axis activity after exposure to ethanol in macaques.Methods: Animals were reared with their mothers in social groups (MR, n= 94) or without adults in peer‐only groups (PR, n= 79). At 5 years of age, they received an intravenous infusion of alcohol (2–2.2 g/kg), and the effects of alcohol, sex, and rearing condition on ACTH and cortisol levels were analyzed by ANOVA.Results: Peer‐reared females had higher ACTH levels than did PR males, MR females, and MR males after alcohol infusion. Alcohol‐induced cortisol levels were not affected by sex and rearing condition.Conclusions: These findings suggest that there are sex differences in glucocorticoid negative feedback, pituitary responsivity, or release of ACTH secretagogues among individuals exposed to early life stress and emphasize the importance of considering sex effects when studying LHPA‐axis dysregulation in alcoholism and other stress‐related neuropsychiatric disorders.
Nursing From an Ethanol‐Intoxicated Dam Induces Short‐ and Long‐Term Disruptions in Motor Performance and Enhances Later Self‐Administration of the Drug
Authors: Ponce Luciano F. , Pautassi Ricardo M. , Spear Norman E. , Molina Juan C. 
Published: July 2004

Rationale: During interactions with an ethanol‐intoxicated dam, preweanling rats encode ethanol‐related chemosensory information. These experiences have been observed to enhance subsequent recognition of ethanol's chemosensory properties and to modulate learning about ethanol.Objective: The present study tested the effects of ethanol‐related nursing experiences on motor function in later infancy and adolescence and on ethanol intake during adolescence.Methods: Wistar‐derived rats were reared by dams intragastrically administered with ethanol (2.5 g/kg) or with water during postnatal days (PDs) 3, 5, 7, 9, 11, and 13. Later in infancy or in adolescence, these rats were tested on a motor coordination task (Accelerod) while either sober or acutely intoxicated with ethanol (1 g/kg). During adolescence, animals had simultaneous access to varying ethanol concentrations (3, 4, 5, or 6% v/v) and water.Results: Both infants and adolescents that had been reared by ethanol‐intoxicated dams exhibited dramatic behavioral impairments in the Accelerod task when compared with the offspring of water control dams. Ethanol intoxication disrupted motor performance in both age groups, but this effect was independent of prior maternal treatment. When tested for voluntary ethanol intake as adolescents, those with prior nursing experiences with an intoxicated dam ingested more ethanol than adolescents reared by sober dams.Conclusions: Early experiences with alcohol comprising interactions with an alcohol‐intoxicated dam result in motor impairment and enhanced ethanol intake later in life.
Anxiety‐Like Behavior in Mice in Two Apparatuses During Withdrawal From Chronic Ethanol Vapor Inhalation
Authors: Kliethermes C L. , Cronise K , Crabbe J C. 
Published: July 2004

Background: Anxiety during ethanol withdrawal may be a factor in relapse to alcohol abuse and dependence. Animal models of ethanol withdrawal have typically used forced consumption of an ethanol‐containing liquid diet to induce dependence. Ethanol vapor inhalation offers an advantage over liquid diet consumption in that the onset of withdrawal can be temporally controlled more precisely, allowing studies of the development of withdrawal symptoms.Methods: The purpose of the current study was to induce ethanol dependence in mice using an inhalation procedure and to assess withdrawal anxiety symptoms behaviorally in the elevated zero maze and in the light/dark box. Male and female mice were exposed to 3 days of ethanol vapors. Anxiety‐like behavior was measured on the elevated zero maze and light/dark box at multiple time points during withdrawal.Results: Mice experiencing ethanol withdrawal demonstrated increased anxiety‐like behaviors relative to control animals in both apparatuses. However, this finding was specific to the procedure used with the elevated zero maze and was strongly influenced by sex in the light/dark box.Conclusions: Ethanol vapor inhalation appears to be a valid tool for the study of withdrawal‐induced anxiety.
Alcohol Reduces GM1 Ganglioside Content in the Serum of Inbred Mouse Strains
Authors: Saito Mitsuo , Saito Mariko , Cooper Thomas B. , Vadasz Csaba 
Published: July 2004

Background: Endogenous and exogenous gangliosides in the plasma affect physiologic and pathologic processes such as angiogenesis and atherogenesis. However, the genetic and environmental factors that regulate the expression of plasma gangliosides are not well known. As shown in the liver and the brain, profiles of gangliosides in the plasma may be strain‐specific and can be altered by intake of alcohol. Therefore, we analyzed serum gangliosides derived from inbred mouse strains with and without alcohol treatment.Methods: C57BL/6ByJ (B6By) and BALB/cJ mice (60–70 days old) were injected with 20% alcohol (1–6 g/kg) or saline intraperitoneally, and the ganglioside content of the serum, liver, and cerebellum was measured 4 hr after the injection. Also, the effect of oral alcohol self‐administration for 18 days with escalating (3–12%) concentrations of alcohol on the serum GM1 content was studied in B6By mice. The quantification of GM1 was performed with a thin‐layer chromatography‐staining procedure using a cholera toxin B subunit, and the content of other gangliosides was measured after staining with resorcinol reagent.Results: We found that basal GM1 (containing N‐glycolylneuraminic acid) content in the serum of BALB/cJ mice (4.8 ± 0.26 ng/μl) was 25 times higher than that of B6By mice (0.19 ± 0.01 ng/μl); the major ganglioside in both strains was GM2. The ganglioside profile in the liver was similar to that of the serum, and the GM1 content in BALB/cJ was nine times higher than that of B6By. Both injection and oral self‐administration of alcohol lowered GM1 levels in the serum.Conclusions: Endogenous ganglioside profiles in the serum are under genetic control among inbred mouse strains, and they can be altered by acute and chronic alcohol administration. These genetic and alcohol‐induced differences in the plasma gangliosides, which appear to reflect ganglioside metabolism in the liver, may affect alcohol‐related behaviors and pathologic processes.
On durable goods markets with entry and adverse selection
Authors: Janssen Maarten , Roy Santanu 
Published: July 2004

Abstract.  We investigate the nature of trading and sorting induced by the dynamic price mechanism in a competitive durable good market with adverse selection and exogenous entry of traders over time. The model is a dynamic version of Akerlof (1970). Identical cohorts of durable goods, whose quality is known only to potential sellers, enter the market over time. We show that there exists a cyclical equilibrium where all goods are traded within a finite number of periods after entry. Market failure is reflected in the length of waiting time before trade. The model also provides an explanation of market fluctuations. JEL classification: D82A propos des marchés de biens durables quand il y a entrée de nouveaux commerçants et sélection adverse.  Les auteurs analysent la nature du commerce et du triage engendrés par le mécanisme dynamique des prix dans un marché concurrentiel de biens durables quand il y a sélection adverse et entrée exogène de nouveaux commerçants dans le temps. Ce modèle est une version dynamique du modèle d’Akerlof (1970). Des cohortes identiques de biens durables, dont la qualité est connue seulement des vendeurs potentiels, arrivent sur le marché dans le temps. Il semble qu’il y ait plus de commerce actif que ce qui est prévu par un modèle statique. En particulier, on montre qu’il existe un équilibre cyclique où tous les biens sont transigés à l’intérieur d’un nombre fini de périodes après leur arrivage et que, à chaque phase du cycle, l’éventail de qualité des biens transigés s’accroît. Les commerçants qui transigent des produits de plus haute qualité attendent plus longtemps et l’imperfection du marché se traduit par la longueur de temps d’attente avant la transaction. Le modèle fournit aussi une explication des fluctuations du marché.
HYPERTENSION IN HEMODIALYSIS PATIENTS: Blood Pressure Measurement in Hemodialysis Patients
Authors: Lazar Andrew E. , Smith Michael C. , Rahman Mahboob 
Published: July 2004

ABSTRACTMeasurement of blood pressure (BP) poses some unique challenges in hemodialysis patients. Timing of BP measurement in relation to dialysis, changes in interdialytic weight gain, and inconsistent BP measurement technique in dialysis units contribute to the variability of BP readings in this population. This may contribute to the equivocal relationship between hypertension and cardiovascular outcomes documented in several epidemiologic studies in this population. Home BP readings are promising, but need to be validated as a measure of the burden of hypertension in this population. It is important to standardize BP measurement in all hemodialysis units according to published guidelines to improve the management of hypertension. Future research studies should carefully validate the technique used to measure BP.
HYPERTENSION IN HEMODIALYSIS PATIENTS: Ambulatory Blood Pressure Monitoring in Hemodialysis Patients: A Critique and Literature Review
Authors: Covic Adrian , Haydar Ali A. , Goldsmith David 
Published: July 2004

ABSTRACTAmbulatory blood pressure (ABP) monitoring has been in use for nearly four decades. In that time, the advantages of using a more reproducible and accurate method to assess the true contribution of blood pressure to the cardiovascular risk profile of patients have steadily become more clearly established, balanced by the additional expense and expertise involved. In nephrology, and in particular in dialysis patients, there are significant difficulties in accurately registering truly representative blood pressure values and understanding the relationship between blood pressure, end‐organ damage, and patient mortality. This arises because of the way in which hemodialysis acutely changes blood pressure values as well as the widespread abnormality of diurnal blood pressure rhythm seen in dialysis patients. Use of ABP monitoring can go some way to overcoming these obstacles. In this review we critically examine the use of ABP monitoring in the understanding of blood pressure control in dialysis patients.
HYPERTENSION IN HEMODIALYSIS PATIENTS: Role of Sodium and Volume in the Pathogenesis of Hypertension in Hemodialysis
Authors: Wilson Jimmy , Shah Tariq , Nissenson Allen R. 
Published: July 2004

ABSTRACTHypertension is a common finding in chronic hemodialysis (HD) patients. Cardiovascular (CV) disease is the leading cause of death in this population, and hypertension is a significant risk factor for CV events. Understanding the etiology of hypertension in chronic HD patients is critical in order to optimize treatment and reduce the morbidity and mortality associated with hypertension. Although the pathogenesis of hypertension in HD patients is multifactorial, two of the major risk factors are increased extracellular volume and sodium intake. Control of extracellular volume has been shown to normalize blood pressure (BP), but this normalization lags behind the extracellular volume contraction (“lag phenomenon”). A sodium load leads to an increase in BP by causing an increase in extracellular volume, resulting in a transient increase in cardiac output and an increase in total peripheral resistance. Sodium may be implicated in the hypertension of end‐stage renal disease (ESRD) patients through hypervolemia‐independent mechanisms. Aggressive control of extracellular volume and dietary sodium intake can normalize BP in chronic HD patients and reduce the morbidity associated with hypertension‐related CV disease.