Changes in Pro-Inflammatory Markers in Detoxifying Chronic Alcohol Abusers, Divided by Lesch Typology, Reflect Cognitive Dysfunction.

Aim: To investigate pro-inflammatory markers in the blood and associate with cognitive impairment.

Methods: Il-6 and ferritin were assayed in the blood of 27 patients, divided according to Lesch typology, at the commencement and after 21 days of detoxification, together with a battery of cognitive tests.

Results: A significantly higher mean level of IL-6 was present in the blood of patients with Lesch typology 1 compared to the other typologies 2 and 3 on admission to the Detoxification Ward which did not alter significantly after detoxification.

Influence of adolescent heavy session drinking on the systemic and brain innate immune system.

Aims: The aim of the study was to evaluate rat models of intermittent alcohol abuse (heavy session/'heavy session' drinking) in relation to inflammatory changes in specific brain regions as well as in the periphery. Furthermore, the study was aimed to assess whether there are inflammatory changes in the blood of human intermittent alcohol abusers who might be associated with changes in neuronal circuitry in the brain, as assessed by functional magnetic resonance imaging (fMRI), which cause adverse effects on memory and learning.

Methods: Various regimes of intermittent alcohol administration have been used in rat models, which vary with respect to the dose and duration of ethanol administration as well as the time of abstinence.

Increased cortical activity in binge drinkers during working memory task: a preliminary assessment through a functional magnetic resonance imaging study.

Background: Cerebral dysfunction is a common feature of both chronic alcohol abusers and binge drinkers. Here, we aimed to study whether, at equated behavioral performance levels, binge drinkers exhibited increased neural activity while performing simple cognitive tasks.

Methods: Thirty-two participants (16 binge drinkers and 16 matched controls) were scanned using functional magnetic resonance imaging (fMRI) while performing an n-back working memory task.

Binge drinking +/- chronic nicotine administration alters extracellular glutamate and arginine levels in the nucleus accumbens of adult male and female Wistar rats.

Aims: The effect of 'binge drinking' coupled or not with chronic nicotine administration on nucleus accumbens (NAc) glutamate, arginine, taurine and hydroxyl radical levels has been investigated in these present studies.

Methods And Results: Ethanol, 2 or 3 g/kg, has been administered to male or female adult rats in a 'binge-type' regime for 3 weeks, +/- nicotine, and changes in glutamate, arginine and taurine content in the NAc, assayed by microdialysis after a further dose of ethanol. The basal concentration of NAc glutamate increased 8-fold in the female adult rats but did not change significantly after further doses of ethanol.

Anti-inflammatory actions of a taurine analogue, ethane β-sultam, in phagocytic cells, in vivo and in vitro.

The ability of a taurine prodrug, ethane β-sultam, to reduce cellular inflammation has been investigated, in vitro, in primary cultures of alveolar macrophages and an immortilised N9 microglial cell line and in vivo in an animal model of inflammation and control rats. Ethane β-sultam showed enhanced ability to reduce the inflammatory response in alveolar macrophages, as assayed by the lipopolysaccharide-stimulated-nitric oxide release, (LPS stimulated-NO), in comparison to taurine both in vitro (10 nM, 50 nM) and in vivo (0.15 mmol/kg/day by gavage).

Laboratory models available to study alcohol-induced organ damage and immune variations: choosing the appropriate model.

The morbidity and mortality resulting from alcohol-related diseases globally impose a substantive cost to society. To minimize the financial burden on society and improve the quality of life for individuals suffering from the ill effects of alcohol abuse, substantial research in the alcohol field is focused on understanding the mechanisms by which alcohol-related diseases develop and progress. Since ethical concerns and inherent difficulties limit the amount of alcohol abuse research that can be performed in humans, most studies are performed in laboratory animals.

Neuro-inflammation induced in the hippocampus of 'binge drinking' rats may be mediated by elevated extracellular glutamate content.

The neuropathological and immune changes induced in the brain by 'binge drinking' have been investigated in a rat model. Evidence of neuro-inflammation was identified in the 'binge drinking' rat model of alcohol abuse after 3 weeks of administration of 2 or 3 g/kg ethanol (EtOH), three times per day for two consecutive days, followed by 5 days of abstinence: Firstly, alveolar macrophages, isolated from these animals, showed significant increases in inducible nitric oxide synthase, as assayed by nitrite release, both before and after lipopolysaccaharide stimulation. Secondly, significant numbers of activated microglia were present in the dentate gyrus region of the hippocampus of the 'binge drinking' model, after major histocompatibility complex class II staining, by comparison with the control.

The influence of chronic nicotine administration on behavioural and neurochemical parameters in male and female rats after repeated binge drinking exposure.

Aims: The possible interaction between nicotine and 'binge drinking' in eliciting changes in behavioural patterns of 'binge drinking' rats as well as nucleus accumbens (NAc) glutamate levels has been investigated in these present studies.

Methods: Adult or adolescent male and female rats received ethanol, 2 g/kg or 3 g/kg, by gavage in a 'binge drinking' regimen (3 times/day over a 6 h period, for 2 days followed by 5 days of abstinence) combined with or without nicotine, 0.3 g/kg, for either a 5-week (adult) or a 4-week (adolescent) period.

Biochemical and neurotransmitter changes implicated in alcohol-induced brain damage in chronic or 'binge drinking' alcohol abuse.

The brain damage, which occurs after either chronic alcoholization or binge drinking regimes, shows distinct biochemical and neurotransmitter differences. An excessive amount of glutamate is released into specific brain regions during binge drinking (in excess of 4- to 5-fold of the normal basal concentration) that is not evident during periods of excessive alcohol consumption in chronic alcohol abusers. Increases in glutamate release are only observed during the initial stages of withdrawal from chronic alcoholism ( approximately 2- to 3-fold) due to alterations in the sensitivities of the NMDA receptors.

Breath alcohol level and plasma amino acids: a comparison between older and younger chronic alcohol-dependent patients.

Aim: The aim of the present study is to examine the distribution of plasma excitatory and inhibitory amino acids, according to the age and current breath alcohol levels (BrAl+/-), of alcohol-dependent patients.

Participants And Methods: 78 alcohol-dependent patients (mean age=46.2+/-11 years, men/women=54/24) were clinically tested, including the determination of the major excitatory as well as inhibitory amino acids.

Neurochemical pathways involved in the protective effects of nicotine and ethanol in preventing the development of Parkinson's disease: potential targets for the development of new therapeutic agents.

In this short review, neurochemical targets are identified where nicotine, and possibly ethanol, may interact to prevent the occurrence of Parkinson's disease. These are (a) the nicotinic acetycholine receptors present in the nigrostriatal area or on the surface of microglia, (b) monoamine oxidases and (c) inducible nitric oxide synthase. If such induced changes can be verified in clinical studies, this may help in the design of new therapeutic drugs which may be of relevance to diminish the incidence and perhaps the progression of the debilitating condition of Parkinson's disease.

Nicotine increases ethanol preference but decreases locomotor activity during the initial stages of chronic ethanol withdrawal.

Aim: The ability of nicotine to modify withdrawal symptoms in rats chronically treated with alcohol, with respect to locomotor activity and ethanol or nicotine preference, has been evaluated in these studies.

Methods And Results: Preliminary studies showed that locomotor activity increased 8-9 h after withdrawal from chronic nicotine intoxication, which was dose specific; it occurred in rats administered 0.15 mg/kg or 0.

Functional characteristics of TauA binding protein from TauABC Escherichia coli system.

Although TauA shares few common characteristics with other known periplasmic binding protein, TauA is a putative periplasmic binding protein, part of tauABCD gene cluster involved in sulfonate transport in sulphate starvation condition. This protein was expressed in E. coli BL 21 and purified before to assess its binding functionalities.

SR147778, a CB1 cannabinoid receptor antagonist, suppresses ethanol preference in chronically alcoholized Wistar rats.

This study investigated the effect of the new CB1 cannabinoid receptor antagonist, SR147778, on ethanol preference in chronically alcoholized Wistar rats. In study 1, SR147778, at doses of 0.3, 1, or 10 mg/kg/day (mg/kg/d) intraperitonealy (ip), was administered during chronic pulmonary ethanol intoxication for 30 days.

Nicotine-induced changes of glutamate and arginine in naive and chronically alcoholized rats: an in vivo microdialysis study.

The effects of nicotine, when administered either acutely or chronically, at doses of 0.15, 0.3 or 0.

Glutamic acid in withdrawal and weaning in patients classified according to Cloninger's and Lesch's typologies.

Aims: Though glutamic acid is well known as a working excitatory in the CNS, its impact on the modulation of alcohol withdrawal symptoms and withdrawal fits are not yet clear. The study has been undertaken to examine the levels of glutamic acid in chronic alcohol-dependent patients at different stages of alcohol withdrawal and weaning and to examine any existence of any differences according to Cloninger's and Lesch's typologies.

Patients And Methods: One hundred and fifty-nine alcohol-dependent patients were assessed according to Cloninger's and Lesch's typologies and related to abstinence duration, age, and gender.

Production of reactive oxygen species following acute ethanol or acetaldehyde and its reduction by acamprosate in chronically alcoholized rats.

The salicylate trap method, combined with microdialysis, has been used to validate whether reactive oxygen species, particularly hydroxyl radicals, ((*)OH), are generated in the hippocampus of male Wistar rats after acute intraperitoneal administration of either ethanol, 2 and 3 g/kg, or acetaldehyde, 200 mg, or during the initial stages of ethanol withdrawal after chronic ethanol intoxication. Salicylate (5 mM) was infused into the hippocampus via the microdialysis probe and the products of its metabolism by hydroxyl radical, particularly 2,3-dihydroxybenzoic acid (2,3-DHBA) as well as 2,5-dihydroxybenzoic acid (2,5-DHBA) assayed by HPLC (High Pressure Liquid Chromatography). Acetaldehyde, 200 mg/kg, and the higher acute dose of ethanol, 3 g/kg, induced transitory increases in 2,3-DHBA and 2,5-DHBA microdialysate content.

Neuroprotective and abstinence-promoting effects of acamprosate: elucidating the mechanism of action.

Acamprosate is an abstinence-promoting drug widely used in the treatment of alcohol dependence but which has a mechanism of action that has remained obscure for many years. Recently, evidence has emerged that this drug may interact with excitatory glutamatergic neurotransmission in general and as an antagonist of the metabotropic glutamate receptor subtype 5 (mGluR5) in particular. These findings provide, for the first time, a satisfactory, unifying hypothesis that can bring together and explain the diverse neurochemical effects of acamprosate.

Nicotine increases microdialysate brain amino acid concentrations and induces conditioned place preference.

The action of nicotine on the nicotinic receptor-mediated release of inhibitory and excitatory acids in the nucleus accumbens, NAC, of freely moving rats was studied in order to clarify their effects' on reinforcing behavior as estimated by conditioned place preference (CPP). Using the technique of microdialysis, intraperitoneal (i.p.

Effects of CB1 cannabinoid receptor blockade on ethanol preference after chronic alcohol administration combined with repeated re-exposures and withdrawals.

Aims: The cannabinoid CB1 receptor antagonist, SR141716A, differentially affects the ethanol preference of chronically alcoholized rats when administered during cycles of ethanol exposure and withdrawal. In this study, ethanol preference was investigated in chronically alcoholized rats that underwent regular withdrawal periods during which the brain cannabinoid CB(1) receptor antagonist, SR141716A, was administered.

Methods: The cannabinoid receptor antagonist SR141716A, 3 or 10 mg/kg/day, was administered i.

Imbalance between neuroexcitatory and neuroinhibitory amino acids causes craving for ethanol.

Long-term exposure to ethanol leads to an imbalance in different excitatory and inhibitory amino acids. When ethanol consumption is reduced or completely stopped, these imbalances in different amino acids and neurotransmitters are behaviorally expressed in the form of ethanol withdrawal. Glutamate, a major excitatory amino acid, and GABA, a major inhibitory amino acid, are responsible, at least partly, for ethanol withdrawal symptoms.

Challenges to medications development in treating alcohol dependence: an international perspective.

Few medications for treating alcohol dependence exist. Greater partnership is needed between academia and the pharmaceutical industry to develop, licence and market efficacious medications for treating alcohol dependence. Methodologies that span the divide between preclinical and large-scale clinical studies need to be developed in order to provide sufficient information on safety, toleration, drug-interaction profile and efficacy, with which to guide development decisions.