Intravenous Alcohol Research Articles

Pharmacogenetics of Naltrexone in Asian Americans: A Randomized Placebo-Controlled Laboratory Study

Recent clinical and laboratory studies have shown that the effects of naltrexone for alcoholism may be moderated by the Asn40Asp single-nucleotide polymorphism (SNP) of the μ-opioid receptor gene (OPRM1). Allele frequencies for this polymorphism, however, have been shown to vary substantially as a function of ethnic background, such that individuals of Asian descent are more likely to carry the minor (Asp40) allele. The objective of this study is to test the naltrexone pharmacogenetic effects of the Asn40Asp SNP in a sample of Asian Americans. This study consists of a double-blinded, randomized, placebo-controlled laboratory trial of naltrexone. Participants (n=35, 10 females; 13 Asn40Asn and 22 Asp40 carriers) were non-treatment-seeking heavy drinkers recruited from the community. After taking naltrexone or placebo, participants completed an intravenous alcohol administration session. The primary outcome measures were subjective intoxication and alcohol craving. Results suggested that Asp40 carriers experienced greater alcohol-induced sedation, subjective intoxication, and lower alcohol craving on naltrexone, as compared to placebo, and to Asn40 homozygotes. There results were maintained when controlling for ALDH2 (rs671) and ADH1B (rs1229984) markers and when examining the three levels of OPRM1 genotype, thereby supporting an OPRM1 gene dose response. These findings provide a much-needed extension of previous studies of naltrexone pharmacogenetics to individuals of Asian descent, an ethnic group more likely to express the minor allele putatively associated with improved biobehavioral and clinical response to this medication. These findings help further delineate the biobehavioral mechanisms of naltrexone and its pharmacogenetics.

Pharmacodynamic effects of intravenous alcohol on hepatic and gonadal hormones: influence of age and sex.

Growth hormone (GH)-insulin-like growth factor-1 (IGF-1) axis and gonadal hormones demonstrate extensively associated regulation; however, little is known about the effects of acute alcohol exposure on these hormones. This study examined the effects of intravenous alcohol on the GH-IGF-1 axis and gonadal hormone concentrations, and the influence of age and sex on their regulation. Forty-eight healthy volunteers (24 men and 24 women each in the 21 to 25 and 55 to 65 year age groups) underwent a 2-session single-blinded study. Subjects received in randomized counter-balanced order, alcohol infusions, individually computed based on a physiologically based pharmacokinetic model, to maintain a steady-state ("clamped") exposure of 50 mg% or saline for 3 hours in separate sessions. Blood samples collected at baseline and postinfusion in each session were assayed for levels of GH, IGF-1, free testosterone, and estradiol. Acute alcohol administration resulted in changes in gonadal hormones that differed by sex. Change in free testosterone showed a significant treatment × baseline interaction (p < 0.001), indicating that alcohol-induced suppression of testosterone occurred predominantly in men. On the other hand, change in estradiol showed a significant treatment × sex interaction (p = 0.028), indicating that alcohol-induced increases in estradiol occurred predominantly in women. There was a trend for alcohol-induced decreases in IGF-1 levels. Change in GH showed a significant main effect of baseline (p < 0.001) and a trend for treatment by baseline interaction, suggesting an alcohol-induced decrease in individuals with high baseline GH values. There was also a significant main effect of sex (p = 0.046) indicating that men had greater changes in GH across treatment compared with women. Alcohol induced a complex pattern of hormonal responses that varied between younger and older men and women. Some of the observed sex-based differences may help improve our understanding of the greater susceptibility to alcohol-related hepatic damage seen in women.

Bidirectional Interactions Between Acute Psychosocial Stress and Acute Intravenous Alcohol in Healthy Men

The biological mechanisms by which acute stress increases alcohol consumption are unclear. One potential mechanism is that stress acts by altering the pharmacological and subjective effects of alcohol. Acute stress produces a cascade of physiological and psychological effects, each with a distinctive time course. In this study, we investigated whether different phases of response to an acute stress alter the subjective effects of intravenous alcohol, by administering the drug at 2 different times after the stress. Healthy men (n = 25) participated in 2 sessions: 1 with the Trier Social Stress Test and the other with a nonstressful control task, each followed by infusions of intravenous alcohol (targeting 40 mg% in 5 minutes) and placebo. One group of participants received alcohol within 1 minute of completing the tasks (Alc0, n = 11), followed by placebo 30 minutes later. In the other group (Alc30, n = 14), the order of alcohol and placebo infusions was reversed. Subjective effects (i.e., anxiety, stimulation, want more) and physiological measures (heart rate, blood pressure, salivary cortisol) were measured before and at repeated intervals after the tasks and infusions. Stress did not change the subjective effects of alcohol in either group. However, when individual differences in alcohol responses were considered, stress differentially altered the stimulant-like and sedative effects of alcohol. Among individuals who exhibited predominantly stimulant responses to alcohol in the nonstressful condition, stress decreased the stimulant-like effects of alcohol and "wanting more." By contrast, among participants who did not report stimulation after alcohol in the control session, stress decreased the sedative effects and increased "want more." In addition, alcohol administered immediately after the Trier Social Stress Test dampened cortisol responses yet prolonged negative subjective responses to the stress. These findings demonstrate that there are bidirectional relationships between alcohol and stress. Alcohol influences responses to stress, and stress changes reactions to alcohol, depending on an individual's pattern of response to alcohol. This study highlights the fact that stress-alcohol interactions vary among individual drinkers, suggesting that the effects of stress on motivation to drink alcohol may also differ between individuals.

Disseminated Septic Emboli, Septic Thrombosis of the Vena Cava and the Common Iliac and Renal Veins, and Retroperitoneal Abscess Secondary to Pyogenic Spondylitis of the Lumbar Spine

Pyogenic spondylitis is an infection of the spine that can include the disc, bone, the epidural space, and adjacent structures1,2. With adequate clinical suspicion and appropriate diagnostic evaluation, most pyogenic spine infections can be managed with culture-specific antibiotics2,3. However, in certain cases, surgery may be necessary to perform an open biopsy or treat a clinically relevant abscess, spinal instability, a severe deformity, or a neurologic deficit; surgery may also be necessary because of the failure of nonoperative treatment1-3. Septic thrombosis of the vena cava is a rare disease entity that causes substantial morbidity and mortality from septicemia and septic emboli4. Most commonly, septic thrombosis of the vena cava occurs as a complication of prolonged central venous catheterization4,5. Other, uncommon causes include inflammatory processes that extend to the wall of the vena cava6-9. We present here a case of pyogenic spondylitis and disseminated septicemia with septic thrombosis of the vena cava, the common iliac vein, and the renal vein. The patient was informed that the data concerning this case would be submitted for publication. A fifty-six-year-old woman was transferred to our emergency department with a sudden onset of sepsis, with dyspnea, a stuporous mentality, and weakness of both lower extremities. She had been generally in a good state of health until two weeks previously, when she developed lower back pain. She underwent nonoperative treatment for lower back pain during those previous two weeks, and she was given antibiotic treatment (ceftriaxone) for a fever that suddenly developed two days before arrival in our emergency room. She had had diabetes mellitus and high blood pressure for many years. She had no history of intravenous drug or alcohol abuse. There was no …

Milk Fat Globule EGF Factor 8 Attenuates Sepsis-Induced Apoptosis and Organ Injury in Alcohol-Intoxicated Rats

Despite advances in our understanding of excessive alcohol-intake-related tissue injury and modernization of the management of septic patients, high morbidity and mortality caused by infectious diseases in alcohol abusers remain a prominent challenge. Our previous studies have shown that milk fat globule epidermal growth factor-factor VIII (MFG-E8), a protein required to opsonize apoptotic cells for phagocytosis, is protective in inflammation. However, it remains unknown whether MFG-E8 ameliorates sepsis-induced apoptosis and organ injury in alcohol-intoxicated rats. The purpose of this study was to determine whether recombinant murine MFG-E8 (rmMFG-E8) attenuates organ injury after acute alcohol exposure and subsequent sepsis. Acute alcohol intoxication was induced in male adult rats by a bolus injection of intravenous alcohol at 1.75 g/kg BW, followed by an intravenous infusion of 300 mg/kg BW/h of alcohol for 10 hours. Sepsis was induced at the end of 10-hour alcohol infusion by cecal ligation and puncture (CLP). rmMFG-E8 or vehicle (normal saline) was administered intravenously 3 times (i.e., at the beginning of alcohol injection, the beginning of CLP, and 10 hours post-CLP) at a dose of 20 microg/kg BW each. Blood and tissue samples were collected 20 hours after CLP in alcoholic animals for various measurements. Acute alcohol exposure per se did not affect the production of MFG-E8; however, it primed the animal and enhanced sepsis-induced MFG-E8 downregulation in the spleen. Administration of rmMFG-E8 reduces alcohol/sepsis-induced apoptosis in the spleen, lungs, and liver. In addition, administration of rmMFG-E8 after alcohol exposure and subsequent sepsis decreases circulating levels of TNF-alpha and interleukin-6 and attenuates organ injury. rmMFG-E8 attenuates sepsis-induced apoptosis and organ injury in alcohol-intoxicated rats.

Should mood during intravenous alcohol administration be studied as a bi- or unipolar phenomenon? a pilot study

In this study, alcohol was administered intravenously to study whether its effects on mood should preferably be studied as a bi- or unipolar phenomenon. This was studied in a double-blind, placebo-balanced, design on six healthy male volunteers. Of the three bipolar aspects of mood (calmness, activity, and pleasantness), only calmness was significantly affected by intravenous alcohol. In contrast, there were significant differences between alcohol and placebo for five of the six unipolar indexes. This support the hypothesis that subjective effects of alcohol on mood are preferably studied with self-ratings that allows positive and negative aspects to be analyzed separately. Further, our data suggest that the effects of alcohol are primarily on negative aspects of mood rather than on positive.

Platelet monoamine oxidase activity predicts alcohol sensitivity and voluntary alcohol intake in rhesus monkeys

Platelet monoamine oxidase B (MAO-B) has been proposed to be a biological marker for the properties of monoamine systems, with low activity being associated with vulnerability for high scores on personality traits such as sensation seeking, monotony avoidance, and impulsiveness, as well as for vulnerability for alcoholism. In the present study, platelet MAO-B activity was analysed in 78 rhesus macaques, and its relation to voluntary alcohol intake and behaviours after intravenous alcohol administration was observed.Monkeys with low platelet MAO-B activity had low levels of 5-hydroxyindole acetic acid in cerebrospinal fluid and showed excessive aggression after alcohol administration. A novel finding was that animals with low platelet MAO-B activity showed less intoxication following alcohol administration. As we have shown previously, they also voluntarily consumed more alcohol. We here replicate results from studies on both humans and non-human primates, showing the utility of platelet MAO as a marker for risk behaviours and alcohol abuse. Furthermore, we link platelet MAO activity to alcohol sensitivity.

Alcohol‐Induced Electrical Remodeling: Effects of Sustained Short‐Term Ethanol Infusion on Ion Currents in Rabbit Atrium

In some patients, above-average alcohol consumption before occurrence of atrial fibrillation (AF) in terms of a "holiday heart syndrome" (HHS) can be determined. There is evidence that long before development of apparent alcohol-induced cardiomyopathy, above-average alcohol consumption generates an arrhythmogenic substrate which abets the onset of AF. Changes of atrial current densities in terms of an electrical remodeling after sustained short-term ethanol infusion in rabbits as a potential part of HHS pathophysiology were examined in this study. Rabbits of the ethanol group (EG) received sustained short-term intravenous alcohol infusion for 120 hours (during infusion period, blood alcohol level did not fall below 158 mg/dl), whereas NaCl 0.9% was infused in the placebo group (PG). Using patch clamp technique in whole-cell mode, atrial current densities were measured and compared between both groups. Ethanol infusion did not alter current densities of I(to) [58.7 +/- 5.0 pA/pF (PG, n = 20 cells) vs. 53.9 +/- 5.0 pA/pF (EG, n = 24)], I(sus) [11.3 +/- 1.4 pA/pF (PG, n = 20) vs. 10.2 +/- 1.0 pA/pF (EG, n = 24)], and I(K1) [-1.6 +/- 0.3 pA/pF (PG, n = 17) vs. -2.0 +/- 0.3 pA/pF (EG, n = 22)]. However, alcohol infusion resulted in a remarkable reduction of I(Ca,L) current densities [-28.4 +/- 1.8 pA/pF (PG, n = 20) vs. -15.2 +/- 1.4 pA/pF (EG, n = 22)] and I(Na) [-75.4 +/- 3.6 pA/pF (PG, n = 17) vs. -35.4 +/- 4.4 pA/pF (EG, n = 21)], respectively. Sustained short-term ethanol infusion in rabbits alters atrial current densities. HHS might be favored by alcohol-induced atrial electrical remodeling.

Comparison of risk factors among blood donors, volunteers and replacement individuals, infected or not by hepatitis C virus

Hepatitis C is transmitted primarily parenterally by contaminated blood and is often associated with: intravenous drug abuse, invasive procedures, blood transfusions, acupuncture, tattooing, and alcohol and tobacco use. This study aimed to quantify and evaluate the risk factors among blood donors, volunteer blood donors and replacement individuals, infected or not by the C virus. The main transmission routes of C virus were identified in 55 men and 25 women (GI) monitored by the Ambulatory Unit of the Department of Tropical Diseases, Botucatu Medical School, and in 24 men and 26 women (GII), all active blood donors at the Bauru State Hospital Transfusional Agency. Both groups were similar in: tobacco and alcohol consumption, sexual behavior, tattooing and illicit drug use. The duration of alcohol and tobacco consumption and blood transfusions in GI were longer, whereas the option for steady partners, condom use, disposable materials and piercings were predominant in GII. In conclusion, the risk factors for hepatitis C demonstrate the necessity of health policies that act on the primary and secondary prevention levels (respectively, reduction of infection incidence and hepatopathy risk).

Effects of naltrexone on cortisol levels in heavy drinkers

The primary objectives of this study were to: (a) examine the neuroendocrine effects of naltrexone vs. placebo by comparing serum cortisol levels; and (b) test the biobehavioral correlates of naltrexone-induced changes in cortisol. Non-treatment seeking heavy drinkers ( n = 37) completed two intravenous alcohol administrations, one after naltrexone (50 mg) and one after placebo. Cortisol levels were measured at baseline and after alcohol intake (BrAC = 0.06 g/dl) on both sessions, as were subjective responses to alcohol. Analyses revealed that naltrexone significantly raised overall cortisol levels compared to placebo. Cortisol levels decreased during alcohol administration and a stronger decrease was observed in the naltrexone condition. Cortisol levels were, in turn, inversely related to some of alcohol's the reinforcing effects (i.e., alcohol ‘high,’ vigor) and positively associated with some of its unpleasant effects (i.e., sedation and subjective intoxication). These results suggest that naltrexone alters cortisol levels in heavy drinkers and that its effects on subjective responses to alcohol may be related, in part, to naltrexone's ability to activate the HPA-axis.

Effects of Naltrexone During the Descending Limb of the Blood Alcohol Curve

The neuropharmacological effects of alcohol are known to vary by limb of the blood alcohol curve, yet human laboratory studies of alcoholism pharmacotherapies have largely failed to consider limb of intoxication when examining medication effects on subjective responses to alcohol. This study examined the effects of naltrexone compared to placebo on subjective responses to alcohol at the descending limb of the blood alcohol curve following a controlled intravenous (IV) alcohol administration. Non-treatment-seeking hazardous drinkers (n = 38) completed two double-blind counterbalanced IV alcohol challenge sessions, one after taking naltrexone (50 mg) for three days and one after taking a placebo for three days. During each session, participants reported on subjective responses to alcohol during the descending limb of the blood alcohol curve. Analyses revealed significant main effects of naltrexone, reflecting significantly decreased alcohol-induced stimulation, craving, vigor, positive mood, and alcohol "high" and increased tension as compared to placebo. These findings suggest that naltrexone may exert some of its therapeutic effects via alterations to experiential aspects of intoxication during the descending limb of alcohol intoxication. Additionally, these results highlight the potential utility of considering limb of blood alcohol curve when examining the mechanisms of action of pharmacotherapies thought to alter subjective responses to alcohol.

Human γ‐aminobutyric acid A receptor α2 gene moderates the acute effects of alcohol and brain mRNA expression

Gamma-aminobutyric acid A (GABA(A)) receptors moderate several of the behavioral effects of alcohol. In fact, recent studies have shown an association between the gene for the alpha2-subunit of the GABA(A) receptor (GABRA2) and alcoholism. In the present study, we examined the functional relevance of the GABRA2 gene in alcohol dependence by assessing brain GABRA2 mRNA and GABA(A)alpha2-subunit protein levels in post-mortem prefrontal cortical tissue collected from control and alcohol-dependent individuals. In addition, using an endophenotype approach, we tested whether the GABRA2 gene moderates sensitivity to the acute effects of alcohol in two independent samples from distinct human alcohol challenge studies. Results indicated that GABRA2 mRNA levels significantly differed by GABRA2 genotype. GABRA2 single nucleotide polymorphisms (rs573400, rs279871 and rs279858) were significantly associated with sensitivity to the acute effects of alcohol. Specifically, there was a significant main effect of GABRA2 x breath alcohol concentration on several measures of subjective responses to alcohol, including the hedonic value of alcohol. Importantly, reanalysis of a previous intravenous alcohol administration study confirmed the results of the oral alcohol challenge study. In summary, these results extend previous findings and provide new insights into the putative biobehavioral mechanisms that may moderate the association between the GABRA2 gene, sensitivity to the acute effects of alcohol and ultimately alcohol dependence.

Effects of Naltrexone on Alcohol Sensitivity and Genetic Moderators of Medication Response

Clinical trials have suggested a modest effect of naltrexone as a pharmacotherapy for alcoholism, and a recent study has suggested that the effects may be moderated by variations in the mu-opioid receptor gene (OPRM1). However, the mechanism by which naltrexone may be differentially effective as a function of the OPRM1 genotype is unclear. (1) To replicate and expand on the association between the A118G single nucleotide polymorphism(SNP) of the OPRM1 gene and alcohol sensitivity, (2) to examine the effects of naltrexone on alcohol sensitivity, and (3) to test the A118G SNP of the OPRM1 gene as a moderator of the effects of naltrexone on alcohol sensitivity. A within-subject, double-blind, placebo-controlled laboratory trial of naltrexone. Participants were recruited from the community. Non-treatment-seeking heavy drinkers were enrolled in the study. Prospective genotyping was conducted to oversample for the genetic variant of interest. Intervention After taking naltrexone (50 mg) or placebo, participants completed an intravenous alcohol challenge session in which they were assessed at baseline and at each of the 3 target breath alcohol concentrations: 0.02, 0.04, and 0.06 mg/L. The Biphasic Alcohol Effects Scale, the Alcohol Urge Questionnaire, the Profile of Mood States, and the Alcohol Rating Scale were administered. Individuals with at least 1 copy of the G allele reported lower alcohol craving and higher alcohol-induced "high" across rising breath alcohol concentrations. Naltrexone was found to blunt alcohol's effects on stimulation, positive mood, craving, and enjoyment. The effects of naltrexone on blunting alcohol-induced high were stronger among individuals with the G allele. This study advances the knowledge of mechanisms of action of naltrexone and genetic moderators of response to this pharmacotherapy.

Pharmacological effects of naltrexone and intravenous alcohol on craving for cigarettes among light smokers: a pilot study

Although naltrexone has been widely researched in the context of drinking and smoking behaviors, with each substance studied separately, little is known about the effects of naltrexone on craving for cigarettes during alcohol intoxication. The present study used a within-subjects double-blind placebo-controlled design to (1) examine the effects of alcohol, administered intravenously, on craving for cigarettes; (2) test the effects of naltrexone on cigarette craving during alcohol intoxication; and (3) examine the relationship between craving for alcohol and cigarettes across rising breath alcohol concentrations (BrACs). Heavy drinking light smokers completed two counterbalanced intravenous alcohol challenge sessions, one after taking naltrexone (50 mg) for 3 days and one after taking a placebo for 3 days. During each session, participants reported on their craving for alcohol and cigarettes. Analyses revealed a significant positive effect of BrAC on urge to smoke as well as a BrAC x Medication interaction. Specifically, the linear relationship between BrAC and urge to smoke was significantly weaker in the naltrexone condition, as compared to placebo. There was also a positive association between urge to drink and urge to smoke, and this relationship was moderated by BrAC. These findings demonstrate that the pharmacological effects of alcohol alone induce craving for cigarettes and that naltrexone blunts the progression of craving for cigarettes during alcohol intoxication. These results highlight the potential clinical utility of naltrexone for heavy drinkers trying to quit smoking.

Nonparametric Extraction of Transient Changes in Neurotransmitter Concentration From Dynamic PET Data

We have developed a nonparametric approach to the analysis of dynamic positron emission tomography (PET) data for extracting temporal characteristics of the change in endogenous neurotransmitter concentration in the brain. An algebraic method based on singular value decomposition (SVD) was applied to simulated data under both rest (neurotransmitter at baseline) and activated (transient neurotransmitter release) conditions. The resulting signals are related to the integral of the change in free neurotransmitter concentration in the tissue. Therefore, a specially designed minimum mean-square error (MMSE) filter must be applied to the signals to recover the desired temporal pattern of neurotransmitter change. To test the method, we simulated sets of realistic time activity curves representing uptake of [11C]raclopride, a dopamine (DA) receptor antagonist, in brain regions, under baseline and dopamine-release conditions. Our tests considered two scenarios: 1) a spatially homogeneous pattern with all voxels in the activated state presenting an identical DA signal; 2) a spatially heterogeneous pattern in which different DA signals were contained in different families of voxels. In the first case, we demonstrated that the timing of a single DA peak can be accurately identified to within 1 min and that two distinct neurotransmitter peaks can be distinguished. In the second case, separate peaks of activation separated by as little as 5 min can be distinguished. A decrease in blood flow during activation could not account for our findings. We applied the method to human PET data acquired with [11C]raclopride in the presence of transiently elevated DA due to intravenous (IV) alcohol. Our results for an area of the nucleus accumbens-a region relevant to alcohol consumption-agreed with a model-based method for estimating the DA response. SVD-based analysis of dynamic PET data promises a completely noninvasive and model-independent technique for determining the dynamics of a neurotransmitter response to cognitive or pharmacological stimuli. Our results indicate that the method is robust enough for application to voxel-by-voxel data.

Risk factors for alcohol misuse: Examining heart rate reactivity to alcohol, alcohol sensitivity, and personality constructs

Objective Heart rate reactivity to alcohol has been conceptualized as an index of alcohol-induced reward and has been associated with a sensation seeking personality profile. The goal of this study is to expand on previous findings regarding the significance of heart rate reactivity to alcohol while examining convergent lines of research on alcohol sensitivity, the rewarding effects of alcohol, and personality constructs. Methods Participants ( N = 47) were heavy drinkers who completed an intravenous alcohol challenge protocol. Results Analyses revealed a significant negative relationship between heart rate reactivity and alcohol-induced sedation and subjective intoxication. Heart rate reactivity was positively related to self-reported alcohol-induced vigor and to impulsivity and sensation seeking scores. Conclusions Taken together, these results suggest that individuals with heightened heart rate reactivity to alcohol appear to be more sensitive to the invigorating properties of alcohol, while being less sensitive to the sedative and unpleasant effects of alcohol intoxication. These findings have implications to the conceptualization of heart rate reactivity to alcohol as a biobehavioral marker of alcohol sensitivity.

The effect of acute ethanol administration on the exocrine pancreatic secretion of the pig.

The acute effect of intravenous and intragastric alcohol on exocrine pancreatic secretion was studied in pigs with chronic pancreatic and gastric fistulas. A new H-type pancreatic cannula was designed for the study. With intravenous alcohol and the gastric fistula open, increased gastric acid secretion occurred but pancreatic enzyme output was inhibited. When acid was allowed to inter the duodenum by closing the gastric fistula, intravenous alcohol produced a secretin-like effect of increased pancreatic volume and bicarbonate secretion. Intragastric alcohol caused an increase in volume, bicarbonate and enzyme output. This was probably due initially to direct gastroduodenal stimulation as the same response occurred following intragastric mannitol of similar volume, pH and osmolality. The subsequently sustained increase in volume and bicarbonate was possibly a secondary secretin-like response following absorption of alcohol. It is concluded that the pig pancreas responds to alcohol as has been described in other animals. The use of a single model has allowed clarification of various phases of response invoking the effects of secretin, gastric and glucagon.

Effect of Donors??? Intravenous Drug Use, Cigarette Smoking, and Alcohol Dependence on Kidney Transplant Outcome

The shortage of organ donors for kidney transplants has made the expansion of the kidney donor pool a clinically significant issue. Previous studies suggest that kidneys from donors with a history of intravenous (IV) drug, cigarette, and/or alcohol use are considered to be a risky choice. However, these kidneys could potentially be used and expand the kidney supply pool if no evidence shows their association with adverse transplant outcomes. This study analyzed the United Network for Organ Sharing dataset from 1994 to 1999 using Kaplan-Meier survival analysis and Cox modeling. The effects on transplant outcome (graft and recipient survival) were examined with respect to the donors' IV drug use, cigarette smoking, and alcohol dependency. Covariates including the recipient variables, the donor variables, and the transplant procedure variables were included in the Cox models. The results show that the donors' history of cigarette smoking is a statistically significant risk factor for both graft survival (hazard ratio=1.05, P<0.05) and recipient survival (1.06, P<0.05), whereas neither IV drug use nor alcohol dependency had significant adverse impact on graft or recipient survival. Assuming that adequate testing for potential infections is performed, there is no evidence to support avoiding the kidneys from donors with IV drug use or alcohol dependency in transplantation. Utilizing these kidneys would clearly expand the potential pool of donor organs.

The effect of a low dose of alcohol on allopregnanolone serum concentrations across the menstrual cycle in women with severe premenstrual syndrome and controls

Neurosteroids have been proposed to play an important role in the interaction between alcohol and GABA(A) receptors and for the symptomatology of premenstrual dysphoric disorder (PMDD). The primary aim of this study was to investigate possible alcohol-induced changes in allopregnanolone serum concentrations across different menstrual cycle phases in women with severe premenstrual syndrome (PMS) and controls. The allopregnanolone and cortisol responses to a low-dose of alcohol were evaluated in 14 women with and 12 women without severe premenstrual syndrome in the follicular and late luteal phases. The effect of a 30-min intravenous alcohol infusion (0.2 g/kg) on allopregnanolone and cortisol serum concentrations was compared to placebo, and compared between cycle phases and groups. Blood samples for measuring allopregnanolone were taken at baseline 25, 55, and 75 min after the start of the alcohol infusion. In the late luteal phase, the alcohol infusion decreased allopregnanolone levels, compared to baseline levels as well as to placebo. The difference in allopregnanolone levels between alcohol and placebo was evident 25 min (P < 0.01), 55 min (P < 0.01), and 75 min (P < 0.05) after start of the infusion. There was no change in allopregnanolone levels during the alcohol infusion in the follicular phase. Also, no difference in alcohol-induced allopregnanolone response between PMS patients and control subjects was detected. Cortisol levels declined during both the placebo and alcohol infusion, but did not differ with respect to which infusion had been given. During the late luteal phase, independent of PMS diagnosis, the low-dose alcohol infusion resulted in decreasing peripheral allopregnanolone levels.

Dopamine D2 Receptor Availability is Associated with Subjective Responses to Alcohol

The mesolimbic dopaminergic system is thought to mediate alcohol abuse and dependence. Determining the relationship between in vivo dopamine and the subjective response to alcohol could improve understanding of the mechanisms that lead to alcohol abuse and dependence. Here, we examined the relationship between dopamine D2 receptors in the nucleus accumbens and scores of perceived "high" and "intoxication" during an intravenous (IV) alcohol infusion. Nine healthy control subjects received [C]raclopride PET scanning at baseline. Eight subjects received a second [C]raclopride scan during a pharmacodynamically modeled and controlled rise of IV alcohol, followed by steady state (60 mg% +/- 5 mg%) alcohol infusion. Numerical ratings of "high" and "intoxication" were tested for correlations with measures of dopaminergic function. Baseline D2 receptor availability in the left nucleus accumbens was significantly correlated with peak perceived "intoxication" (p = 0.02) and marginally correlated with peak perceived "high" (p = 0.07). Resting D2 receptor availability may predict healthy subject responses to alcohol exposure.