Analysis of QT Dispersion, Corrected QT Dispersion, and P-Wave Dispersion Values in Alcohol Use Disorder Patients With Excessive Alcohol Use.

OBJECTIVE: To identify the changes in QT dispersion (QTd), corrected QTd (QTcd), and P-wave dispersion (Pd) values with long-term alcohol abuse that could lead to severe ventricular arrhythmia, atrial fibrillation, and sudden death in alcohol use disorder (AUD) patients with excessive alcohol use. METHODS: This cross-sectional study included 48 individuals diagnosed with AUD based on DSM-5 criteria. Patients with a history of psychiatric diseases were not included. The control group comprised 48 individuals with no psychiatric diagnosis who did not abuse alcohol or other substances. Participants with body mass index > 24.9 kg/m² were excluded. Twelve-derivation electrocardiograms (ECG) were obtained from all participants. RESULTS: The mean ± SD age was 44.35 ± 10.24 years in the AUD group and 40.90 ± 13.45 years in the control group. There was no significant difference between the groups based on age (P = .108). There was a significant difference between the groups based on smoking status (P = .000). The mean ± SD period of alcohol use was 20.71 ± 12.04 years, and the alcohol intake was 5.88 ± 1.65 units/d. The AUD group demonstrated elevations in all ECG measures (QTd: 46.56 vs 26.67 ms, QTcd: 54.25 vs 30.88 ms, Pd: 44.69 vs 28.54 ms, all P = .000). CONCLUSIONS: AUD patients with excessive alcohol use had a higher risk of arrhythmia and sudden death compared to the control group. Consideration of ECG and referral to cardiologic examinations would contribute to the follow-up and health of patients with AUD.

Gender Equality, Drinking Cultures and Second-Hand Harms from Alcohol in the 50 US States.

BACKGROUND: Gender inequality and cultures of binge drinking may increase the risk of second-hand harms from alcohol. METHODS: Using the 2014-2015 National Alcohol Survey and 2015 National Alcohol's Harm to Others Survey (N = 7792), we examine associations of state-level gender equality measures (contraceptive access, abortion rights, women's economic equality) and binge drinking cultures (rates of men's and women's binge drinking) with individual-level indicators of second-hand harms by drinking strangers and partners/spouses. RESULTS: In main effects models, only male binge drinking was associated with greater odds of harms from drinking strangers. There were significant interactions of gender equality with male binge drinking: High male binge drinking rates were more strongly associated with stranger-perpetrated harms in states low on contraceptive access or abortion rights compared to states high on these measures. Conversely, male binge drinking was more strongly associated with spouse/partner-perpetrated second-hand harms in states with more economic equality, compared to states lower on this measure. CONCLUSIONS: Detrimental effects of high male binge drinking rates may be modified by gender equality. Targeted interventions may reduce alcohol-related harms experienced by women in states with high rates of male binge drinking. Restrictions in access to contraception and abortion may exacerbate harms due to men's drinking.

Effects of Clavulanic Acid Treatment on Reinstatement to Methamphetamine, Glial Glutamate Transporters, and mGluR 2/3 Expression in P Rats Exposed to Ethanol.

Evidence demonstrated that the glutamatergic system is implicated in mediating relapse to several drugs of abuse, including methamphetamine (METH). Glutamate homeostasis is maintained by a number of glutamate transporters, such as glutamate transporter type 1 (GLT-1), cystine/glutamate transporter (xCT), and glutamate aspartate transporter (GLAST). In addition, group II metabotropic glutamate receptors (mGluR2/3) were found to be implicated in relapse-seeking behavior. Ample evidence showed that ß-lactam antibiotics are effective in upregulating GLT-1 and xCT expression, thus improving glutamate homeostasis and attenuating relapse to drugs of abuse. In this study, we investigated the reinstatement of METH using conditioned place preference (CPP) in male alcohol-preferring (P) rats exposed to home-cage free choice ethanol drinking. Here, we tested the effect of clavulanic acid (CA), a ß-lactam, on the reinstatement of METH-seeking and ethanol drinking. In addition, we examined the expression of GLT-1, xCT, and GLAST as well as metabotropic glutamate receptor (mGluR2/3) in the nucleus accumbens (NAc) shell, NAc core, and dorsomedial prefrontal cortex (dmPFC). A priming i.p. injection of METH reinstated preference in METH-paired chamber following extinction. Chronic exposure to ethanol decreased the expression of GLT-1 and xCT in the NAc shell, but not in the NAc core or dmPFC. CA treatment blocked the reinstatement of METH-seeking, decreased ethanol intake, and restored the expression of GLT-1 and xCT in the NAc shell. In addition, the expression of mGluR2/3 was increased by CA treatment in the NAc shell and dmPFC. These findings suggest that these glutamate transporters and mGluR2/3 might be potential therapeutic targets for the attenuation of reinstatement to METH-seeking.

Binge Drinking's Effects on the Body.

Studies have focused on the effects of chronic alcohol consumption and the mechanisms of tissue injury underlying alcoholic hepatitis and cirrhosis, with less focus on the pathophysiological consequences of binge alcohol consumption. Alcohol binge drinking prevalence continues to rise, particularly among individuals ages 18 to 24. However, it is also frequent in individuals ages 65 and older. High blood alcohol levels achieved with this pattern of alcohol consumption are of particular concern, as alcohol can permeate to virtually all tissues in the body, resulting in significant alterations in organ function, which leads to multisystemic pathophysiological consequences. In addition to the pattern, amount, and frequency of alcohol consumption, additional factors, including the type of alcoholic beverage, may contribute differentially to the risk for alcohol-induced tissue injury. Preclinical and translational research strategies are needed to enhance our understanding of the effects of binge alcohol drinking, particularly for individuals with a history of chronic alcohol consumption. Identification of underlying pathophysiological processes responsible for tissue and organ injury can lead to development of preventive or therapeutic interventions to reduce the health care burden associated with binge alcohol drinking.

Cellular Abnormalities and Emerging Biomarkers in Alcohol-Associated Liver Disease.

Alcohol-associated liver disease (AALD) is the third most common preventable cause for disease burden and mortality in the US. AALD, including alcoholic hepatitis (AH), contributes to half of admissions from decompensated liver disease and 20% of all liver transplants in the US. Peripheral blood cells contribute to systemic inflammation, oxidative stress, mitochondrial dysfunction, and fibrosis in AALD and AH. Alcohol dysregulates function of lymphocytes, neutrophils, monocytes, and tissue macrophages of the innate immune system. These alterations in turn can modulate adaptive immune responses. In this review, we describe these disruptive effects of alcohol on cells of the innate and adaptive immune system and focus on cellular-based emerging biomarkers on diagnosis and prognosis of patients with AALD and AH.

Focus on aggressive behaviour in mental illness.

Background: Aggression is a behaviour with evolutionary origins, but in today's society it is often both destructive and maladaptive. Increase of aggressive behaviour has been observed in a number of serious mental illnesses, and it represents a clinical challenge for mental healthcare provider. These phenomena can lead to harmful behaviours, including violence, thus representing a serious public health concern. Aggression is often a reason for psychiatric hospitalization, and it often leads to prolonged hospital stays, suffering by patients and their victims, and increased stigmatization. Moreover, it has an effect on healthcare use and costs in terms of longer length of stay, more readmissions and higher drug use. Materials and methods: In this review, based on a selective search of 2010-2016 pertinent literature on PubMed, we analyze and summarize information from original articles, reviews, and book chapters about aggression and psychiatric disorders, discussing neurobiological basis and therapy of aggressive behaviour. Results: A great challenge has been revealed regarding the neurobiology of aggression, and an integration of this body of knowledge will ultimately improve clinical diagnostics and therapeutic interventions. The great heterogeneity of aggressive behaviour still hampers our understanding of its causal mechanisms. Still, over the past years, the identification of specific subtypes of aggression has released possibilities for new and individualized treatment approaches. Conclusions: Neuroimaging studies may help to further elucidate the interrelationship between neurocognitive functioning, personality traits, and antisocial and violent behaviour. Recent studies point toward manipulable neurobehavioral targets and suggest that cognitive, pharmacological, neuromodulatory, and neurofeedback treatment approaches can be developed to ameliorate urgency and aggression in schizophrenia. These combined approaches could improve treatment efficacy. As current pharmacological and therapeutic interventions are effective but imperfect, new insights into the neurobiology of aggression will reveal novel avenues for treatment of this destructive and costly behaviour.

Occurrence, Predictors, and Prognosis of Alcohol Withdrawal Syndrome and Delirium Tremens Following Traumatic Injury.

OBJECTIVES: We sought to determine occurrence, predictors, and prognosis of alcohol withdrawal syndrome and delirium tremens in patients with traumatic injury. DESIGN: Retrospective multicenter cohort study. SETTING: Three U.S. trauma centers. PATIENTS: Twenty-eight thousand one hundred one trauma patients admitted from 2010-2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Measures included occurrence of alcohol withdrawal syndrome and delirium tremens, injury characteristics, risk factors for alcohol withdrawal syndrome, clinical outcomes, pharmacologic treatment for alcohol withdrawal syndrome, and Clinical Institute Withdrawal Assessment for Alcohol, Revised (CIWA-Ar) scores. Alcohol withdrawal syndrome severity was defined by CIWA-Ar score as minimal (< 10), moderate (10-20), and severe (> 20). Alcohol withdrawal syndrome developed in 0.88% (n = 246), including 12% minimal, 36% moderate, and 53% severe. Alcohol withdrawal syndrome progressed to delirium tremens in 11%. Before adjustment, alcohol withdrawal syndrome severity was associated with injury severity, hypokalemia, baseline CIWA-Ar score, and established alcohol withdrawal syndrome risk factors. Logistic regression identified the following predictors of delirium tremens: baseline CIWA-Ar score greater than or equal to 10 (odds ratio, 6.05; p = 0.02) and age greater than or equal to 55 (odds ratio, 3.24; p = 0.03). In patients with severe alcohol withdrawal syndrome, severe head injury also predicted progression to delirium tremens (odds ratio, 6.08; p = 0.01), and hypokalemia was borderline significant (odds ratio, 3.23; p = 0.07). Clinical outcomes of hospital length of stay, ICU length of stay, and alcohol withdrawal syndrome complications differed significantly by alcohol withdrawal syndrome severity and were worse with more severe manifestations of alcohol withdrawal syndrome. Mortality also significantly differed by alcohol withdrawal syndrome severity but was only greater in patients who progressed to delirium tremens (11.1%; p = 0.02); otherwise, there were no differences in mortality by severity (4%, 4%, and 0% by minimal, moderate, and severe alcohol withdrawal syndrome). CONCLUSIONS: Trauma patients with alcohol withdrawal syndrome experience a high occurrence of delirium tremens that is associated with significant mortality. These data demonstrate the predictive ability of baseline CIWA-Ar score, age, and severe head injury for developing delirium tremens.

Comorbilidad psiquiátrica y valores plasmáticos de 2-acilgliceroles en consumidores de alcohol en tratamiento ambulatorio. Análisis de las diferencias de género / Psychiatric comorbidity and plasma levels of 2-acyl-glycerols in outpatient treatment alcohol users. Analysis of gender differences

La adicción al alcohol se asocia con una elevada comorbilidad psiquiátrica que complica el tratamiento, siendo necesaria una fenotipación clínica objetiva de estos pacientes para optimizar la atención y mejorar el pronóstico. El presente estudio aborda este problema mediante los siguientes objetivos: a) estimar la prevalencia y tipos de comorbilidad psiquiátrica de una muestra de pacientes que buscan tratamiento por uso de alcohol, b) describir las diferencias de género en su presentación y c) analizar los valores plasmáticos de 2-acilgliceroles (incluyendo el endocannabinoide 2-araquidonilglicerol), estudiando su posible valor como biomarcador de alcoholismo y/o comorbilidad psiquiátrica. Para ello se reclutaron 162 pacientes evaluados con la entrevista semiestructurada PRISM, para evaluar la presencia de comorbilidad y su carácter primario o inducido. Los resultados obtenidos indican que la presencia de psicopatología se asoció a un mayor número de criterios de abuso y dependencia de alcohol Se encontraron diferencias de género tanto en la comorbilidad psiquiátrica, especialmente en trastornos del estado de ánimo. La prevalencia de comorbilidad psiquiátrica encontrada a lo largo de la vida fue del 68,5%, destacando los trastornos del estado ánimo (37%), y seguidos por el trastorno por déficit de atención (24,7%, monitorizado específicamente por la entrevista WURS) y los trastornos de ansiedad (17,9%). Entre los trastornos del estado de ánimo y psicóticos fueron más frecuentes los inducidos, mientras que en los trastornos de ansiedad los primarios fueron más prevalentes. Además, se encontraron concentraciones disminuidas significativamente de 2-acilgliceroles en pacientes con trastornos de ansiedad comórbidos diagnosticados en el último año

Alcohol addiction is associated with high psychiatric comorbidity. Objective stratification of patients is necessary to optimize care and improve prognosis. The present study is designed to gain insights into this challenge by addressing the following objectives: a) to estimate the prevalence of psychiatric comorbidities in a sample of outpatients seeking treatment for alcohol use disorder, b) to describe the existence of gender differences and c) to validate 2-acyl-glycerols as biomarkers of alcohol use disorder and/or psychiatric comorbidity. One hundred and sixty-two patients were recruited and evaluated with the semistructured interview PRISM. The presence of psychopathology was associated with a greater number of criteria for alcohol abuse and dependence according to DSM-IV-TR. We found gender differences in psychiatric comorbidity, e.g., mood disorder, as well as in comorbid substance use disorders. The prevalence of lifetime psychiatric comorbidity was 68.5%, with mood disorders the most frequent (37%), followed by attention deficit disorder (24.7%) and anxiety disorders (17.9%). Substance-induced disorders were more frequent in mood and psychotic disorders, whereas the primary disorders were more prevalent in patients with comorbid anxiety disorders. We found that 2-acyl-glycerols were significantly decreased in comorbid anxiety disorders in alcohol dependent patients in the last year, which makes them a potential biomarker for this psychopathological condition

Chronic Pancreatitis.

Chronic pancreatitis is a debilitating condition often associated with severe abdominal pain and exocrine and endocrine dysfunction. The underlying cause is multifactorial and involves complex interaction of environmental, genetic, and/or other risk factors. The pathology is dependent on the underlying pathogenesis of the disease. This review describes the clinical, gross, and microscopic findings of the main subtypes of chronic pancreatitis: alcoholic chronic pancreatitis, obstructive chronic pancreatitis, paraduodenal ("groove") pancreatitis, pancreatic divisum, autoimmune pancreatitis, and genetic factors associated with chronic pancreatitis. As pancreatic ductal adenocarcinoma may be confused with chronic pancreatitis, the main distinguishing features between these 2 diseases are discussed.

Cross-sectional study on N,N-dimethylformamide (DMF); effects on liver and alcohol intolerance.

PURPOSE: There are still concerns regarding occupational exposure to hepatotoxic DMF. This study was designed to evaluate possible liver damaging effects of DMF under current workplace conditions in synthetic fibres industries. METHODS: Among other laboratory parameters, liver function parameters (alkaline phosphatase (ALP), aspartate aminotransferase, alanine aminotransferase and gamma-glutamyltransferase), the mean corpuscular erythrocyte volume (MCV) and carbohydrate-deficient transferrin (CDT) of the workforce of two companies present at the days of study were investigated. Internal exposure to DMF was assessed via three different biomarkers [sum of N-methylformamide and N-hydroxymethyl-N-methylformamide, N-acetyl-S-(N-carbamoyl)cysteine (AMCC) and 3-methyl-5-isopropylhydantoin (MIH)]. Alcohol consumption was assessed by means of direct ethanol metabolites (ethylglucuronide and ethylsulfate). RESULTS: None of the tested liver enzyme activities showed a positive association with any of the three exposure markers, nor did CDT and MCV. CDT was negatively associated with AMCC and the ALP activity negatively with all three exposure markers. Changes in liver function are seen mainly in conjunction with ethanol consumption but also with increasing body weight and age. MCV was associated with smoking. Almost half of the workers stated to experience alcohol flush reaction. CONCLUSION: The present study indicates that long-term exposure to DMF, which was specified by median urinary AMCC levels of 4.84 mg/g creatinine and DMF haemoglobin adduct levels of 60.5 nmol/MIH/g globin, respectively, does not result in any adverse liver effects. In contrast, these DMF exposure levels still elicit certain alcohol intolerance reactions.

Nest building is a novel method for indexing severity of alcohol withdrawal in mice.

Withdrawal after chronic ethanol (EtOH) affects body temperature, goal-directed behavior and motor function in mice and increases general central nervous system excitability. Nest-building tests have been used to assay these states but to this point have not been employed as measures of EtOH withdrawal severity. We first refined nest-scoring methods using a genetically heterogeneous stock of mice (HS/Npt). Mice were then made physically dependent following three days of chronic EtOH vapor inhalation to produce average blood EtOH concentrations (BECs) of 1.89 mg/mL. EtOH withdrawal affected the progression of nest building over time when mice were tested 2-4 days after removal from three days of chronic exposure to EtOH. In a separate group of mice, chronic EtOH vapor inhalation (BECs 1.84 mg/mL) suppressed nest building over days 1-2 but not days 2-3 of withdrawal. In a following experiment, EtOH withdrawal dose-dependently slowed recovery of nest building for up to 32 h. Finally, we determined that long-lasting nest-building deficits extend to mice undergoing withdrawal from a high dose (4 g/kg) of acute EtOH. Sex differences for nest building were absent following EtOH exposure. In mice naïve to EtOH treatments, male mice had lower pre-test body temperatures and increased nest scores across a two-day testing period compared to females. These results suggest that nest building can be used to assess chronic and acute EtOH withdrawal severity in mice.

Effects of alcohol hangover on simulated highway driving performance.

BACKGROUND: The purpose of this study was to examine the effects of alcohol hangover on simulated highway driving performance. METHODS: Driving performance of forty-two social drinkers was tested the morning following an evening of consuming on average 10.2 (SD = 4.2) alcoholic drinks (alcohol hangover) and on a control day (no alcohol consumed). Subjects performed a standardized 100-km highway driving test in the STISIM driving simulator. In addition to the standard deviation of lateral position (SDLP; i.e., the weaving of the car), lapses of attention were examined. Self-reported driving quality and driving style were scored, as well as mental effort to perform the test, sleepiness before and after driving, and hangover severity. RESULTS: Driving performance was significantly impaired during alcohol hangover as expressed by an SDLP increase of +1.9 cm (t (1,41) = 2.851, p = 0.007), increased number of lapses relative to the control day (7.7 versus 5.3 lapses, t (1,41) = 2.125, p = 0.019), and an increased total lapse time (182.7 versus 127.3 s, p = 0.040). During alcohol hangover, subjects reported their driving quality to be significantly poorer (t (1,41) = 4.840, p = 0.001) and less safe (t (1,41) = 5.078, p = 0.001), wise (t (1,41) = 4.061, p = 0.001), predictable (t (1,41) = 3.475, p = 0.001), and responsible (t (1,41) = 4.122, p = 0.001). Subjects further reported being significantly more tense while driving (t (1,41) = 3.280, p = 0.002), and more effort was needed to perform the driving test (t (1,41) = 2.941, p = 0.001). There was a significant interaction with total sleep time and hangover effects on SDLP and the number of lapses. CONCLUSIONS: In conclusion, driving is significantly impaired during alcohol hangover, as expressed in an elevated SDLP and increased number of lapses. Total sleep time has a significant impact on the magnitude of driving impairment.

Alcohol and bone.

Alcohol is widely consumed across the world in different cultural and social settings. Types of alcohol consumption differ between (a) light, only occasional consumption, (b) heavy chronic alcohol consumption, and (c) binge drinking as seen as a new pattern of alcohol consumption among teenagers and young adults. Heavy alcohol consumption is detrimental to many organs and tissues, including bones. Osteoporosis is regularly mentioned as a secondary consequence of alcoholism, and chronic alcohol abuse is established as an independent risk factor for osteoporosis. The review will present the different mechanisms and effects of alcohol intake on bone mass, bone metabolism, and bone strength, including alcoholism-related "life-style factors" such as malnutrition, lack of exercise, and hormonal changes as additional causative factors, which also contribute to the development of osteoporosis due to alcohol abuse.

An imbalance between VEGF and endostatin underlies impaired angiogenesis in gastric mucosa of aging rats.

Gastric mucosa of aging individuals exhibits increased susceptibility to injury and delayed healing. Our previous studies in young rats showed that healing of mucosal injury depends on and is critically dependent on VEGF and angiogenesis. Since angiogenesis in aging gastric mucosa has not been examined before, in this study we examined the extent to which angiogenesis is impaired in gastric mucosa of aging vs. young rats and determined the underlying mechanisms with a focus on mucosal expression of VEGF (proangiogenic factor) and endostatin (antiangiogenic factor). Aging rats had significantly impaired gastric angiogenesis by ~12-fold, 5-fold, 4-fold, and 3-fold, respectively (vs. young rats; all P < 0.001) at 24, 48, 72, and 120 h following ethanol-induced gastric injury and reduced and delayed healing of mucosal erosions. In gastric mucosa of aging (vs. young) rats at baseline, VEGF expression was significantly reduced, whereas endostatin levels were significantly increased (P < 0.05 and P < 0.01, respectively). In contrast to young rats, gastric mucosal VEGF levels did not increase following ethanol-induced injury in aging rats. MMP-9 enzyme activity was significantly higher in gastric mucosa of aging vs. young rats both at baseline (2.7-fold) and 24 h (3.8-fold) after ethanol injury (both P < 0.001). Since endostatin is generated from collagen XVIII by MMP-9, this finding can explain the mechanism of increased endostatin expression in aging gastric mucosa. The above findings demonstrate that reduced VEGF and increased endostatin result in the impaired angiogenesis and delayed injury healing in gastric mucosa of aging rats.

Alcohol and cardiovascular disease: still unresolved underlying mechanisms.

Alcoholic (ethanol-containing) beverages are consumed by most societies in the world. Low-to-moderate levels of ethanol consumption have been shown to reduce the risk of cardiovascular diseases and atherosclerosis. The decreased risk is likely due to alcohol's favorable pleiotropic effects on lipids, adhesion molecules, platelet activation and oxidative stress. However, there is also an abundance of clinical, experimental and epidemiological evidence showing that chronic high-dose ethanol consumption increases mortality, cardiovascular complications and also the progression of atherosclerosis. This last phenomenon appears to be due to the metabolism of ethanol, that leads to the formation of acetaldehyde, which is oxidized to acetate, leading to the generation of reactive oxygen species (ROS) and a toxic effect of ethanol on the formation of the atherosclerosis plaque. We will here briefly review the mechanisms through which high intakes of ethanol induce the formation of atherosclerotic plaque, focusing on increased oxidative stress as the main underlying mechanism.

GABA: ¿dualidad funcional? Transición durante el neurodesarrollo / GABA: a functional duality? Transition during neurodevelopment

Introducción. El ácido gamma-aminobutírico (GABA) es el principal neurotransmisor de tipo inhibitorio y sus acciones son mediadas por receptores de tipo ionotrópico (GABAA) y metabotrópico (GABAB), ampliamente distribuidos en el tejido nervioso central. Objetivo. Revisar la estructura de los receptores GABA y su implicación en procesos fisiológicos en el sistema nervioso central. Desarrollo. Se aborda el estudio de la estructura y diversidad de los receptores GABA, especialmente durante el neurodesarrollo, y se hace referencia a la naturaleza excitatoria e inhibitoria de la transmisión gabérgica, donde la participación de los cotransportadores NKCC1 y KCC2 tiene un papel clave en dicha dualidad funcional en la transición de un estadio embrionario a uno posnatal. De igual forma, se plasma el interés por los receptores GABA como diana farmacológica de uso clínico, lo que se manifiesta por la presencia de sitios de modulación alostérica poco explorados en dicho complejo-receptor. Conclusiones. El conocimiento fisiológico y farmacológico de la gran diversidad de subunidades que conforman un determinado subtipo de receptor GABA, así como la correcta expresión en tiempo y espacio para garantizar la viabilidad de un organismo, prometen ser la respuesta a trastornos graves y añejos como la epilepsia o la drogadicción, y tan complejos como el neurodesarrollo (AU)

Introduction. Gamma-aminobutyric acid (GABA) is the most important inhibitory-type neurotransmitter and its actions are mediated by ionotropic (GABAA) and metabotropic (GABAB) type receptors, which are widely distributed throughout the tissue of the central nervous system. Aim. To review the structure of GABA receptors and their involvement in physiological processes in the central nervous system. Development. The study addresses the structure and diversity of the GABA receptors, especially during neurodevelopment, and reference is made to the excitatory and inhibitory nature of GABAergic transmission, where the participation of the cotransporters NKCC1 and KCC2 plays a key role in this functional duality in the transition from an embryonic to a postnatal state. Likewise, the interest in GABA receptors as a pharmacological target for clinical use is also discussed. This is manifested by the presence of under-explored allosteric modulation sites in the aforementioned complex-receptor. Conclusions. The physiological and pharmacological knowledge of the great diversity of subunits that make up a particular subtype of GABA receptor, as well as the correct expression in time and space in order to ensure the viability of the organism, promise to be the answer to long-time severe disorders like epilepsy or drug addiction, and such complex ones as neurodevelopment (AU)

Effects of alcohol withdrawal on cardiovascular system.

Alcohol withdrawal syndrome (AWS) develops after cessation of alcohol intake in alcoholic patients characterizing psychiatric symptoms and changes in autonomous nervous systems. We studied cardiovascular changes during different phases of AWS (1, 2, 3 and 10 days after admission for detoxification; n=34) and compared them with those in early recovery (at least 1 month of abstinence; n=30). The results study showed that cardiovascular system underwent significant changes during AWS characterizing the decrease of heart rate, systolic and diastolic blood pressures, and total peripheral resistance. Stroke index was lower during AWS than in early recovery. As the decreased stroke index was compensated by increased heart rate, cardiac index did not differ during AWS from that in early recovery. Increased functioning of noradrenaline (along with other central and peripheral regulating mechanisms) may be an important factor associated with cardiovascular changes in AWS. Normalization of this function after AWS leads to returning of cardiovascular parameters to baseline levels.

Hypothalamic-pituitary-adrenal axis activity, dehydroepiandrosterone sulphate and their relationships with aggression in early and late alcohol withdrawal.

The study aims at investigating the relationship between hypothalamic-pituitary-adrenal (HPA) axis alterations and aggression level in alcoholic patients during early and late alcohol withdrawal. Serum levels of basal cortisol and dehydroepiandrosterone sulphate (DHEAS) were measured three times, and cortisol and DHEAS response to dexamethasone twice during the early and late withdrawal periods in alcohol dependent males (n=30) and once in healthy control males (n=20). Abnormal cortisol non-suppression response to dexamethasone in dexamethasone suppression test (DST) was observed in some proportion of the patients in early withdrawal, which normalized in late withdrawal. The study revealed reduced basal DHEAS levels and reduced DHEAS response to dexamethasone in late withdrawal. When the patients were assessed in two separate groups as high- and low-aggressives, in the high-aggression group abnormality in DST was observed during both early and late withdrawal periods, in the low-aggression group it was observed only in early withdrawal. While basal DHEAS levels were low in the high-aggression group only in early withdrawal, it was reduced in the low-aggression group during late withdrawal period. Some alterations of the HPA axis during alcohol withdrawal might be associated not only with alcohol use per se but also with aggressivity tendency of alcoholic patients.

Commentary: Systems biology and its relevance to alcohol research.

Systems biology, a new scientific discipline, aims to study the behavior of a biological organization or process in order to understand the function of a dynamic system. This commentary will put into perspective topics discussed in this issue of Alcohol Research & Health, provide insight into why alcohol-induced disorders exemplify the kinds of conditions for which a systems biological approach would be fruitful, and discuss the opportunities and challenges facing alcohol researchers.