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In a longitudinal rat model of alcohol consumption, we showed that exposure to alcohol decreased the concentration of glutamate in the prefrontal cortex, whereas a normalization occurred during abstinence. 18F-FPEB PET scans revealed that pre-exposure mGluR5 availability in the nucleus accumbens was associated with future alcohol preference. Finally, alcohol exposure induced a decrease in mGluR5 availability in the bilateral hippocampus and amygdala compared with baseline, and in the hippocampus and striatum compared with saccharin (Figure). ispartof: ADDICTION BIOLOGY vol:24 issue:4 pages:696-706 ispartof: location:United States status: published

Alcohol use disorder (AUD) is characterized by repetitive and uncontrolled intake of alcohol with severe consequences for affected individuals, their families and society as a whole. Numerous studies have implicated brain-derived neurotrophic factor (BDNF) activity in the neurobiology underlying AUD. The BDNF signaling mechanism is complex and depends on two receptor systems, TrkB and p75NTR, which appear to have opposite effects on alcohol seeking behavior in animal models. We recently discovered that the sortilin-related receptor SorCS2 forms complexes with both TrkB and p75NTR and is important for BDNF activity in the developing and adult CNS. Moreover, the SORCS2 gene was recently identified as the top association signal for severity of alcohol withdrawal symptoms. Hence, we speculated that SorCS2 deficient mice would have an altered response to alcohol. The role of SorCS2 in the acute and adapted response to alcohol was therefore investigated by comparing SorCS2 knockout (Sorcs2-/- ) mice to wild type (WT) mice in three paradigms modeling alcohol sensitivity and consumption; alcohol-induced conditioned place preference, two-bottle choice test as well as the behavioral response to alcohol withdrawal. We found that, when compared to the WT mice, (I) Sorcs2-/- mice displayed complete lack of alcohol-induced place preference, (II) when given free choice between water and alcohol, Sorcs2-/- mice consumed less alcohol, and (III) Sorcs2-/- mice showed no handling-induced convulsion in response to alcohol withdrawal following extended alcohol exposure. Taken together, these results show that lack of the alcohol withdrawal risk gene Sorcs2 results in abnormal behavioral response to alcohol in mice. Consequently, SorCS2 may play an important role in the molecular pathways underlying AUD and complications associated with alcohol withdrawal.

Phosphatidylethanol species (PEths) are promising biomarkers of alcohol consumption. Here, we report on the set-up, validation, and application of a novel UHPLC-ESI-MS/MS method for the quantification of PEth 16:0/18:1, PEth 18:1/18:1, and PEth 16:0/16:0 in whole blood (30 mu L) and in venous (V, 30 mu L) or capillary (C, 3 punches (3 mm)) dried blood spots (DBS). The methods were linear from 10 (LLOQ) to 2000 ng/mL for PEth 16:0/18:1, from 10 (LLOQ) to 1940 ng/mL for PEth 18:1/18:1, and from 19 (LLOQ) to 3872 ng/mL for PEth 16:0/16:0. Extraction efficiencies were higher than 55 % (RSD < 18 %) and matrix effects compensated for by IS were between 77 and 125 % (RSD < 10 %). Accuracy, repeatability, and intermediate precision fulfilled acceptance criteria (bias and RSD below 13 %). Validity of the procedure for determination of PEth 16:0/18:1 in blood was demonstrated by the successful participation in a proficiency test. The quantification of PEths in C-DBS was not significantly influenced by the hematocrit, punch localization, or spot volume. The stability of PEths in V-DBS stored at room temperature was demonstrated up to 6 months. The method was applied to authentic samples (whole blood, V-DBS, and C-DBS) from 50 inpatients in alcohol withdrawal and 50 control volunteers. Applying a cut-off value to detect inpatients at 221 ng/mL for PEth 16:0/18:1 provided no false positive results and a good sensitivity (86 %). Comparison of quantitative results (Bland-Altman plot, Passing-Bablok regression, and Wilcoxon signed rank test) revealed that V-DBS and C-DBS were valid alternatives to venous blood for the detection of alcohol consumption.

Aim: To investigate the effect of moderate alcohol consumption on metabolic alterations, inducible nitric oxide synthase (iNOS), immunohistochemical distribution, and morphological damage to penile erectile tissue in rats. Materials and methods: Male Wistar albino rats were divided into 2 groups. Group 1 rats (control group, n = 8) received tap water ad libitum, and group 2 rats (n = 8) were fed with 20% ethanol. Increasing levels of alcohol were given to the rats over 12 weeks. Immunohistochemistry was then performed using the avidin-biotin-peroxidase technique on 5-mu m thickness tissue sections. Stained sections were examined by imaging microscope. Results: Alcohol consumption resulted in a significant increase in iNOS immunoreactivity in the penile erectile tissue. Increased iNOS expression was determined in the tunica albuginea, cavernosal smooth muscle cells, trabeculae of connective tissue, arterioles, and the urethral epithelium. Moreover, chronic alcohol consumption resulted in decreasing serum testosterone and high density lipoprotein (HDL) levels with increasing cholesterol and triglyceride levels. Conclusion: Chronic moderate alcohol consumption can affect penile erectile tissue by increasing iNOS immunoreactivity and induce histopathological damage such as penile fibrosis. These abnormalities are also related to the defense mechanism against morphological damage. Kocaeli University, Kocaeli, TurkeyKocaeli University This work was supported by the Research Fund of Kocaeli University, Kocaeli, Turkey.

Introduction: Helicobacter-induced atrophic gastritis with a hypochlorhydric milieu is a risk factor for gastric cancer. Microbes colonising acid-free stomach oxidise ethanol to acetaldehyde, a recognised group 1 carcinogen. Objective: To assess gastric production of acetaldehyde and its inert condensation product, non-toxic 2-methyl-1,3-thiazolidine-4-carboxylic acid (MTCA), after alcohol intake under treatment with slow-release L-cysteine or placebo. Methods: Seven patients with biopsy-confirmed atrophic gastritis, low serum pepsinogen and high gastrin-17 were studied in a cross-over single-blinded design. On separate days, patients randomly received 200 mg slow-release L-cysteine or placebo with intragastric instillation of 15% (0.3 g/kg) ethanol. After intake, gastric concentrations of ethanol, acetaldehyde, L-cysteine and MTCA were analysed. Results: Administration of L-cysteine increased MTCA (p

OBJECTIVEMorbid obesity is a growing problem worldwide. The current treatment options have limitations regarding effectiveness and complication rates. New treatment modalities are therefore warranted. One of the options is deep brain stimulation (DBS) of the nucleus accumbens (NAC). This review aims to summarize the current knowledge on NAC-DBS for the treatment of morbid obesity.METHODSStudies were obtained from multiple electronic bibliographic databases, supplemented with searches of reference lists. All animal and human studies reporting on the effects of NAC-DBS on body weight in morbidly obese patients were included. Articles found during the search were screened by 2 reviewers, and when deemed applicable, the relevant data were extracted.RESULTSFive relevant animal experimental papers were identified, pointing toward a beneficial effect of high-frequency stimulation of the lateral shell of the NAC. Three human case reports show a beneficial effect of NAC-DBS on body weight in morbidly obese patients.CONCLUSIONSThe available literature supports NAC-DBS to treat morbid obesity. The number of well-conducted animal studies, however, is very limited. Also, the optimal anatomical position of the DBS electrode within the NAC, as well as the optimal stimulation parameters, has not yet been established. These matters need to be addressed before this strategy can be considered for human clinical trials.

OBJECTIVE: Elderly people show an increased risk of acute respiratory infections and their complications. This increased susceptibility may be the result of immunosenescence. If lifestyle factors could influence the risk of the infections, this could result in great public health relevance. We investigated the relation between alcohol consumption, smoking, and physical activity with acute respiratory infections. DESIGN: Prospective observational analysis. SETTING: The study took place between September 1998 - June 2000, in the Wageningen area of The Netherlands. PARTICIPANTS: In total 652 relatively healthy elderly people participated. Participants were noninstitutionalized and 60 years and older. MEASUREMENTS: The lifestyle factors were assessed at baseline by means of standardized and validated questionnaires in the participants. Self-reported respiratory infections were assessed from 1998-2000 by nurse telephone contact, and home visits, and were evaluated by microbiological tests in a subset. RESULTS: We detected 1024 acute respiratory infections among 443 participants, the overall incidence rate (IR) was 1.6 infections per person per year. IR ratio (95% confidence interval) of the infections was 1.31 (1.01, 1.70) for occasional (superior 0 glasses/day

OBJECTIVE: Elderly people show an increased risk of acute respiratory infections and their complications. This increased susceptibility may be the result of immunosenescence. If lifestyle factors could influence the risk of the infections, this could result in great public health relevance. We investigated the relation between alcohol consumption, smoking, and physical activity with acute respiratory infections. DESIGN: Prospective observational analysis. SETTING: The study took place between September 1998 - June 2000, in the Wageningen area of The Netherlands. PARTICIPANTS: In total 652 relatively healthy elderly people participated. Participants were noninstitutionalized and 60 years and older. MEASUREMENTS: The lifestyle factors were assessed at baseline by means of standardized and validated questionnaires in the participants. Self-reported respiratory infections were assessed from 1998-2000 by nurse telephone contact, and home visits, and were evaluated by microbiological tests in a subset. RESULTS: We detected 1024 acute respiratory infections among 443 participants, the overall incidence rate (IR) was 1.6 infections per person per year. IR ratio (95% confidence interval) of the infections was 1.31 (1.01, 1.70) for occasional (superior 0 glasses/day