Evaluation of the influence of alcohol dehydrogenase polymorphisms on alcohol elimination rates in African Americans.

INTRODUCTION: The relationship between alcohol dehydrogenase (ADH) polymorphisms and alcohol use disorders in populations of African descent has not been clearly established. This study examined the effect of ADH1B polymorphisms on alcohol metabolism and subjective response, following intravenous (IV) alcohol administration, and the influence of gender, recent drinking history, and family history of alcoholism (FHA), in nondependent African American drinkers. MATERIALS: The sample included eighty-seven 21- to 35-year-old, light social drinkers of African descent. Participants included 39 sib pairs, 2 sibships with 3 siblings each, and 3 individuals who were not part of a sibship. Participants received infusions via the use of the clamp method that refers to the goal of controlling breath alcohol concentration in 2 randomized sessions at 0.06 g% ethanol and 0 mg% (placebo), and a battery of subjective scales at predefined time points. Dependent measures included alcohol elimination rates (AERs), alcohol disappearance rates (ADRs), subjective measures peak scores, and area under the curve. General linear model and mixed models were performed to examine the relationship between ADH1B genotype, dependent measures, and influence of covariates. RESULTS: Participants with ADH1B1/1 genotypes showed higher number of drinks (p = 0.023) and drinks per drinking day (p = 0.009) compared with the persons with ADH1B1/3 genotype. AER (adjusted for body weight) was higher in ADH1B*1 homozygotes (p = 0.045) compared with ADH1B1/3 heterozygotes. ADR differed significantly between males and females (p = 0.002), regardless of body weight (p = 0.004) and lean body mass (p < 0.001) adjustments. Although a few subjective measures differed across genotype, all measures were higher in alcohol sessions compared with placebo sessions (p < 0.001). These observations were mediated by drinks per drinking day, gender, and FHA. CONCLUSIONS: ADH1B polymorphism had a marginal effect on alcohol pharmacokinetics following IV alcohol administration in nondependent drinkers of African descent. Session (alcohol vs. placebo) and ADH1B genotype did, however, influence subjective response to alcohol with some variation by gender, FHA, and drinks per drinking day.

Alcohol dependence and health care utilization in African Americans.

OBJECTIVE: Ethnic and cultural differences in patterns of alcohol use disorders must be understood in order to address improvement in prevention of such disorders and accessibility to health care services. The purpose of this study was to evaluate factors that influence the utilization of medical and mental health services among alcohol-dependent and non-alcohol-dependent African Americans. METHOD: A cohort of 454 African Americans was evaluated. Alcohol-dependent participants were recruited from various inpatient treatment facilities in the Washington, DC, metropolitan area and through advertisement and word of mouth. Non-alcohol-dependent participants were recruited by advertisements. Each participant was administered the Semi-Structured Assessment for the Genetics of Alcoholism to assess alcohol dependency and the Family History Assessment module to access family history of alcoholism. Xl Test and analysis of variance were used to analyze the data. RESULTS: Alcohol dependence was more prevalent among men, those with lower income, those with less education, and they utilized mental health counseling as opposed to medical-based therapy. Increased reports of medical conditions such as migraine (p<.001), loss of consciousness (p=.001), and sexually transmitted diseases: (p<.001) were also associated with alcohol dependency. Other factors, including visits to inpatient treatment programs, were directly related to incidence of alcohol dependency regardless of gender status (p<.001). CONCLUSIONS: This study suggests an association exists among alcohol dependence, medical conditions, health care, and mental care utilization among African Americans. Future research may benefit from investigating if an association exists between alcohol use disorders and health care utilization for other ethnic groups.

Heritability of level of response and association with recent drinking history in nonalcohol-dependent drinkers.

BACKGROUND: Level of response (LR) to alcohol has been shown to be associated with the risk of developing alcohol dependence and can be measured using the self-rating of the effects of alcohol (SRE) questionnaire. This study examined the heritability of the SRE-measured LR and the relationship between LR and recent alcohol drinking history (RDH) in a predominantly African American nonalcohol-dependent population. METHODS: This was a sibling study of 101 social drinkers aged 21 to 35 years recruited from the Washington, DC metropolitan area. Participants were administered the SRE to assess LR and the timeline followback (TLFB) to assess RDH. The indices of SRE used were total SRE score (SRTT), early drinking SRE score (SRED), regular drinking SRE score (SRRD), and heavy drinking SRE score (SRHD). Pearson's product-moment correlation and linear regression were used to analyze SRE indices and RDH variables (quantity and drinks per drinking occasion). Heritability analysis was conducted using Sequential Oligogenic Linkage Analysis Routines (SOLAR) software with SRE indices as traits of interest. RESULTS: There was a significant relationship between SRE and RDH measures. Drinks per drinking day, maximum drinks, and quantity of drinks were significantly associated with SRTT, SRHD, and SRRD (all p < 0.05). SRTT showed significant heritability (h(2) = 0.67, p = 0.025), however, the SRE subindices (SRED, SRRD, SRHD) were not significantly heritable. Analysis performed in the subset consisting of only African Americans (n = 86) showed similar trends. CONCLUSIONS: LR, as measured by the SRE, is associated with RDH. The high level of heritability of the SRE total score suggests that genetics accounts for a significant proportion of the variation in the LR to alcohol in social drinkers.

Assessing the KING IV Corporate Governance Report in relation to business continuity and resilience.

Within South Africa and on the African continent, the various reports of the KING Committees on Corporate Governance have become guiding principles for organisations in both the public and private sector. This paper focuses on the KING IV report and discusses its relevance to the different but interrelated fields of business continuity, organisational resilience and risk management. The paper suggests that organisations seeking to comply with KING IV will need to familiarise themselves with ISO 22301 and the BCI Good Practice Guidelines, as well as ISO 31000.

Alterations in ethyl alcohol pharmacokinetics during oral consumption of malt liquor beverages in African Americans.

BACKGROUND: Malt liquor (ML) beverages have become increasingly popular among urban minority groups, due partly to their inexpensive price and targeted advertising. We hypothesized that nonfermented by-products contained in ML beverages will alter the pharmacokinetics (PK) and pharmacodynamic (PD) effects of its ethanol content. In addition, we determined the effect of alcohol dehydrogenase (ADH) genotypes on the PK following consumption of ML beverages. METHODS: The study was conducted in 31 healthy adult African-American social drinkers, mean +/- SD age of 22.3 +/- 1.3 years, and weight of 70.7 +/- 10.9 kg. Participants were administered ethanol, in randomized order, 2-weeks apart, in the form of oral ML beverage (6%v/v), or isocaloric solution of diet soda-ethanol (DS-Etoh) beverage (6%v/v). During each session the beverage was consumed over 4 minutes and breath alcohol concentrations (BrAC) as well as subjective and behavioral effects of ethanol were evaluated over 180 minutes. Pharmacokinetic parameters of ethanol were calculated using Michaelis-Menten elimination kinetics. The effect of ML and ADH genotype on PK was evaluated using the Wilcoxon rank-sum test and the Wilcoxon signed rank test, respectively. RESULTS: Results show a slower mean rate of absorption, K(a), (0.12 vs. 0.15 min(-1), p = 0.03) and a longer time to reach maximum concentration, T(max), (28 vs. 23 minute, p < 0.01) for the ML compared with DS-Etoh beverage. The ML beverage resulted in a larger area under the BrAC-time curve compared with DS-Etoh beverage (8.4 vs. 6.8 min g/dl, p = 0.02). There was no difference in the subjective PD effects between the 2 beverages. CONCLUSION: Results show that exposure to ethanol following the consumption of ML beverages is different compared to that following nonmalt beverages in African-Americans. These differences may be related to nonfermented by-products present in commercially available ML products. These PK differences do not appear to result in significant perceived alcohol PD changes, nor are they related to ADH genotype.

Low Vs. High Alcohol: Central Benefits Vs. Detriments.

The dose-dependent effects of alcohol, where the initial euphoric and stimulant effects initiated by the exposure to low ethanol levels can quickly lead to a deadly consequence are well established. Thus, high blood alcohol concentration (BAC), as seen in alcoholics, can cause significant damage to various organs. At low concentrations (e.g., 10 mg% or lower), however, beneficial effects of alcohol, particularly on cardiovascular function have been reported. Although, the latter assertion has been challenged by recent epidemiological studies, protective effects of low alcohol concentrations in vitro and in vivo relevant to the central nervous system (CNS) is well documented. In this review, the mechanism(s) leading to the detrimental effects of high BAC, as well as the beneficial effects of low BAC will be discussed. In addition, gender consideration is touched upon. Although further investigation is clearly warranted, it may be concluded that at least some of the beneficial outcomes of low BAC, including possible neuroprotection and antidepressant-like effects, may be due to elevation of the neurotropic factors and reduction of inflammatory mediators, whereas detrimental outcomes associated with high BAC, including neurotoxicity and depressive-like behavior may be due to reduction in neurotropic factors and elevation of inflammatory mediators. Furthermore, new research strategies are suggested.

Alcohol-Induced Increases in Inflammatory Cytokines Are Attenuated by Nicotine in Region-Selective Manner in Male Rats.

BACKGROUND: Heavy use of alcohol is commonly associated with heavy smoking (nicotine intake). Although many factors, including mood effects of these two drugs may contribute to their co-use, the exact neurobiological underpinnings are far from clear. It is well known that chronic alcohol exposure induces neuroinflammation that may precipitate depressive-like behavior, which is considered an important factor in alcohol relapse. Nicotine, on the other hand, possesses anti-inflammatory and antidepressant effects. PURPOSE: In this study, we sought to determine which proinflammatory markers may be associated with the depressogenic effects of chronic alcohol and whether nicotine pretreatment may normalize these changes. STUDY DESIGN: For this purpose, we treated adult male Wistar rats with alcohol (1.0 g/kg, IP), nicotine (0.3 mg/kg, IP) or their combination once daily for 14 days. Two prominent proinflammatory cytokines (IL-1ß and TNF-α) in two primary brain regions, namely the hippocampus and frontal cortex that are intimately involved in mood regulation, were evaluated. RESULTS: Chronic alcohol resulted in increases in both cytokines in both regions as determined by Western blot. Nicotine completely blocked alcohol-induced effects in the hippocampus, but not in the frontal cortex. These data suggest that nicotine may mitigate the inflammatory effects of alcohol in brain-selective region. Hence, the previously observed depressogenic effects of alcohol and the antidepressant effects of nicotine may at least be partially mediated through manipulations of proinflammatory cytokines in the hippocampus. CONCLUSION: These findings suggest possible therapeutic potential of anti-inflammatory cytokines in combating alcohol-induced depression and/or relapse.

Efficacy of acute administration of nicotine gum in relief of cue-provoked cigarette craving.

RATIONALE: Acute cravings, often provoked by exposure to smoking cues, appear to be important triggers for smoking relapse. Relief of acute craving may therefore be an important step in preventing relapse. OBJECTIVES: This study was undertaken to assess the effectiveness of nicotine gum in relieving acute craving. METHODS: A multi-center, randomized, placebo-controlled study was conducted with smokers ( n=296) who quit by using either active or inactive gum for 3 days. On their third day of abstinence, smokers participated in a laboratory session in which they were exposed to a provocative smoking cue, chewed active or inactive gum, and then rated their craving at 5-min intervals for 35 min. RESULTS: Craving initially decreased in both groups. After 15 min, however, the smokers using active nicotine gum experienced significantly greater craving reductions. CONCLUSIONS: These results suggest that nicotine gum can effectively reduce acute craving following exposure to smoking cues.

Noncompliance leading to drug accumulation resulting in phenytoin toxicity.

Phenytoin is effective in suppressing tonic-clonic and partial seizures, and is widely used for initial therapy, particularly in adults. Ninety percent of phenytoin is protein bound and entirely eliminated by hepatic metabolism. The major metabolite of phenytoin, 5-(p-hydroxyphenyl)-5phenylhy-dantoin (5HPPH) is excreted in the urine. Higher phenytoin levels for a given dose of phenytoin can be seen in alcohol intoxication, hepatic and renal failures, hypoalbuminemia, nephrotic syndrome, trauma, and AIDS. Noncompliance can lead to accumulation of the drug-causing toxicity. We present a patient with acute alcohol intoxication who developed phenytoin toxicity due to noncompliance with the drug.