The Role of Drugs in Alcohol Poisoning and Blackout Events: A Latent Class Analysis of a Residential Treatment Sample.

BACKGROUND: Alcohol can lead to fatal and nonfatal overdose (OD) through its neurobiological inhibitory effects when used alone or with other drugs. Little research has examined alcohol OD characteristics in the context of concomitant drug use. METHODS: This study utilized alcohol OD data (defined as alcohol poisoning, passing out, or blacking out) collected in a large residential addiction treatment facility (N = 660). Latent class analysis identified classes of alcohol OD events based on concomitant drug use at the time of OD. We evaluated correlates of alcohol OD classes, including depression, emergency medical services, and hospitalization, using latent class regression. RESULTS: Only 20% of alcohol ODs involved alcohol alone. Marijuana was the most commonly used drug during the most recent alcohol OD (43.2%), followed by sedatives (27.9%), cocaine or crack (25.9%), prescription opioids (26.1%), and heroin (20%). The final latent class model included 3 classes: no/low drug involvement (61%), moderate drug involvement (33%), and high drug involvement (6%). Relative to the no/low drug involvement class, participants admitted to the hospital were 6.4-fold more likely to be in the high drug involvement class (95% CI: 2.4 to 16.6) and 2.9-fold more likely to be in the moderate drug involvement class (95% CI: 1.2 to 7.2). Participants receiving emergency medical services were more likely to be in the high drug involvement class (aOR: 2.2, 95% CI: 2.2, 1.1 to 4.5) and less likely to be in the moderate drug involvement class (aOR 0.39, 95% CI: 0.2 to 0.96). CONCLUSIONS: Combining drug classes with alcohol prior to OD was common and associated with a higher likelihood of hospitalization. Overdose prevention efforts should address acute risks of alcohol ingestion with other drugs.

Dietary ß-conglycinin prevents acute ethanol-induced fatty liver in mice.

Alcoholic fatty liver is the earliest stage of alcohol-induced liver disease leading to liver cirrhosis. ß-Conglycinin, one of the soy proteins, is known to prevent non-alcoholic fatty liver, hyperlipidemia and obesity. Therefore, we examined whether ß-conglycinin feeding has an effect on the prevention of acute ethanol-induced fatty liver in mice. Male C57BL/6J mice were fed with 20 energy% ß-conglycinin or casein for 4 weeks prior to ethanol administration and were then given ethanol or glucose, as a control, by gavage. Ethanol significantly increased liver triglyceride (TG) in mice fed casein due to the activation of peroxisome proliferator-activated receptor (PPAR) γ2, a nuclear transcription factor known for regulating lipid metabolism and de novo lipogenesis. The liver TG of ethanol-administered ß-conglycinin-fed mice was significantly lower than that in those fed casein, although ethanol increased the amount of liver TG in mice fed ß-conglycinin. The increased levels of PPARγ2 protein and its target gene CD36 in response to an ethanol were not observed in mice fed ß-conglycinin. Moreover, ß-conglycinin decreased the basal expression of de novo lipogenesis-related genes such as stearoyl-CoA desaturase-1, and therefore, the expressions of these genes were lower in the ethanol-administered ß-conglycinin-fed mice than in the casein-fed mice. In conclusion, ß-conglycinin supplementation appears to prevent the development of fatty liver in mice caused by ethanol consumption via the suppression of alcohol-induced activation of PPARγ2 and the downregulation of the basal expression of de novo lipogenesis.

Resveratrol attenuates excessive ethanol exposure induced insulin resistance in rats via improving NAD+ /NADH ratio.

SCOPE: Resveratrol has been shown to improve insulin resistance via activating the NAD+ -dependent deacetylase SIRT1, but the effects of resveratrol on ethanol-induced insulin resistance remain unclear. This study was designed to explore the potential mechanism by which resveratrol ameliorated ethanol-induced insulin resistance, focusing on its regulations on the ratio of NAD+ /NADH and SIRT1 expression. METHODS AND RESULTS: Male Sprague-Dawley rats were fed either control or ethanol liquid diets containing 0.8, 1.6 and 2.4 g/kg·bw ethanol with or without 100 mg/kg·bw resveratrol for 22 weeks. Resveratrol improved ethanol (2.4 g/kg·bw) induced reductions in insulin sensitivity, SIRT1 expression (51%, P < 0.05), NAD+ /NADH ratio (196%, P < 0.01) as well as the expression and activity of ALDH2 while decreased the augmentations in the expression and activity of ADH and CYP2E1. In primary rat hepatocytes, ethanol exposure (25 mmol/L, 24 h) similarly decreased SIRT1 expression and NAD+ /NADH ratio (33%, P < 0.05; 32%, P < 0.01), and 0.1 µmol/L resveratrol treatment reversed these decreases and inhibited the expressions of ADH and CYP2E1. CONCLUSION: Resveratrol exhibits benefits against ethanol-induced insulin resistance via improving the ratio of NAD+ /NADH to regulate SIRT1, which is associated with the modulation of ethanol metabolism enzymes.

Fatal kavalactone intoxication by suicidal intravenous injection.

Kavalactones are a group of compounds found in kava, a beverage or extract prepared from the rhizome of the kava plant (Piper methysticum). Traditionally kava extracts have been used for their anxiolytic and sedative properties. Sales of kava extracts were severely restricted or prohibited in European countries in 2002 following several cases of serious hepatotoxicity. Here we report a case where high concentrations of kavalactones and ethanol were detected in post mortem femoral blood. An injection needle with a 10-mL syringe containing 7.5 mL of slightly yellowish liquid was found next to the victim, and there were numerous needle prints on both lower arms following the venous tracks. No evidence of other cause of death was found in the medico-legal investigation. The case was therefore classified as suicide using an injection of kavalactones intravenously together with alcohol poisoning.

L-Carnitine for the treatment of a calcium channel blocker and metformin poisoning.

INTRODUCTION: The object of the current communication is to discuss the theory and the evidence for the use of L-carnitine in calcium channel blocker and metformin poisonings. CASE REPORT: A 68-year-old male known for hypertension and type II diabetes was admitted to the critical care unit of a community hospital following an overdose of amlodipine and metformin. The patient was intubated, ventilated, and hemodynamically supported with vasopressors. Despite calcium, glucagon, high-dose insulin (HDI), and lipid emulsion for calcium channel blocker and bicarbonate for metabolic acidosis, the patient remained hemodynamically unstable. The patient was considered too unstable to initiate continuous renal replacement therapy; and without access to extracorporeal life support, the administration of L-carnitine was administered as a last resort. One hour after L-carnitine, the norepinephrine requirements started to decrease, the patient began to improve and was subsequently extubated successfully without apparent sequelae in less than 4 days. DISCUSSION: L-Carnitine combined with HDI may have helped with the calcium channel blocker (CCB) poisoning by decreasing insulin resistance, promoting intracellular glucose transport, facilitating the metabolism of free fatty acids, and increasing calcium channel sensitivity. It may have also stimulated oxidative utilization of glucose instead of converting pyruvate into lactate and contributed to decrease lactate production with metformin poisoning.

Dietary grapes (Vitis vinifera) feeding attenuates ethanol-induced oxidative stress in blood and modulates immune functions in mice.

Ethanol metabolism is known to induce overwhelming production of reactive oxygen species (ROS) and also to cause associated immune dysfunction. Several interventional agents of plant origin, in particular fruits and vegetables have been used to counteract these alterations induced by ethanol. In this study, we investigated the efficacy of dietary feeding of skin and flesh of grapes (Vitis vinifera L.) on the alterations in immune and vascular functions in mice with liver abnormalities induced by chronic ethanol consumption. Results revealed that feeding of both grape skin and flesh (2.5 g/kg body wt/day) effectively attenuated the oxidative stress and alterations in immune function and angiogenesis induced by chronic ethanol consumption (1.6 g/kg body wt/day for 12 weeks) in mice. The antioxidant actions of the grape skin and flesh as observed in this study might be attributed to the polyphenols present in the grapes.

Behavioral effects of taurine pretreatment in zebrafish acutely exposed to ethanol.

Taurine (TAU) is an amino sulfonic acid that plays protective roles against neurochemical impairments induced by ethanol (EtOH). Mounting evidence shows the applicability of zebrafish for evaluating locomotor parameters and anxiety-like behavioral phenotypes after EtOH exposure in a large scale manner. In this study, we assess the effects of TAU pretreatment on the behavior of zebrafish in the open tank after acute 1% EtOH (v/v) exposure (20 and 60 min of duration) and on brain alcohol contents. The exposure for 20 min exerted significant anxiolytic effects, which were prevented by 42, 150, and 400 mg/L TAU. Conversely, the 60-min condition induced depressant/sedative effects, in which the changes on vertical activity were associated to modifications on the exploratory profile. Although all TAU concentrations kept locomotor parameters at basal levels, 150 mg/L TAU, did not prevent the impairment on vertical activity of EtOH[60]. Despite the higher brain EtOH content detected in the 60-min exposure, 42, 150, and 400 mg/L TAU attenuated the increase of alcohol content in EtOH[60] group. In conclusion, our data suggest that both protocols of acute EtOH exposure induce significant changes in the spatio-temporal behavior of zebrafish and that TAU may exert a preventive role by antagonizing the effects induced by EtOH possibly due to its neuromodulatory role and also by decreasing brain EtOH levels. The hormetic dose-response of TAU on vertical exploration suggests a complex interaction between TAU and EtOH in the central nervous system.

[Simulation of parameters of alcohol-oxidizing enzyme systems and pathomorphological characteristics in situations of acute ethanol poisoning and ischemic heart disease].

Morphometric characteristics and forensic chemical information used in diagnostics of acute ethanol intoxication and coronary heart disease in conjunction with macro- and microscopic pathomorphological signs of the changes in the heart, liver, and kidneys provide data that may suggest the presence of pathology but do not permit to reliably identify it. In this context, evaluation of activities of alcohol-oxidizing enzyme systems acquires clinical significance. The analysis of correlations between quantitative parameters supplemented by the construction of binary models allows to objectively interpret the conclusions about the cause of death in each concrete case of acute ethanol poisoning and coronary heart disease.

Combining energy drinks and alcohol - a recipe for trouble?

BACKGROUND: Combining energy drinks (such as 'Red Bull(®)') with alcohol is becoming increasingly popular, particularly among young people. However, as yet, limited research has been conducted examining the harms associated with this form of drinking. OBJECTIVE: To review current evidence associated with combining energy drinks with alcohol and provide recommendations for addressing this issue within primary care. DISCUSSION: Combining alcohol with energy drinks can mask the signs of alcohol intoxication, resulting in greater levels of alcohol intake, dehydration, more severe and prolonged hangovers, and alcohol poisoning. It may also increase engagement in risky behaviours (such as drink driving) as well as alcohol related violence. General practitioners should be aware of the harms associated with this pattern of drinking, and provide screening and relevant harm reduction advice.

In-utero exposure to smoking, alcohol, coffee, and tea and risk of strabismus.

In a prospective, population-based cohort study, the authors investigated the effect of in-utero exposure to maternal smoking and consumption of alcohol, coffee, and tea on the risk of strabismus. They reviewed medical records for children in the Danish National Birth Cohort identified through national registers as possibly having strabismus. Relative risk estimates were adjusted for year of birth, social class, maternal smoking, maternal age at birth, and maternal coffee and tea consumption. The authors identified 1,321 cases of strabismus in a cohort of 96,842 Danish children born between 1996 and 2003. Maternal smoking was associated with a significantly elevated risk of strabismus in the child, increasing with number of cigarettes smoked per day (<5 cigarettes/day: relative risk (RR) = 0.95, 95% confidence interval (CI): 0.80, 1.14; 5-<10 cigarettes/day: RR = 1.38, 95% CI: 1.12, 1.70; > or =10 cigarettes/day: RR = 1.90, 95% CI: 1.57, 2.30). Nicotine replacement therapy was not associated with strabismus risk (RR = 1.22, 95% CI: 0.92, 1.61). Light maternal alcohol consumption was inversely associated with strabismus risk, whereas maternal coffee and tea drinking were not associated with strabismus risk. In conclusion, smoking during pregnancy is associated with an increased risk of strabismus in the offspring. Conversely, light alcohol consumption is associated with decreased risk.

Differential effects of acute alcohol on prepulse inhibition and event-related potentials in adolescent and adult Wistar rats.

BACKGROUND: Previous studies have demonstrated that adolescent and adult rats show differential sensitivity to many of the acute effects of alcohol. We recently reported evidence of developmental differences in the effects of acute alcohol on the cortical electroencephalogram. However, it is unclear whether developmental differences are also observed in other neurophysiological and neurobehavioral measurements known to be sensitive to alcohol exposure. The present study determined the age-related effects of acute alcohol on behavioral and event-related potential (ERP) responses to acoustic startle (AS) and prepulse inhibition (PPI). METHODS: Male adolescent and adult Wistar rats were implanted with cortical recording electrodes. The effects of acute alcohol (0.0, 0.75, and 1.5 g/kg) on behavioral and ERP responses to AS and PPI were assessed. RESULTS: Acute alcohol (0.75 and 1.5 g/kg) significantly reduced the behavioral and electrophysiological response to AS in adolescent and adult rats. Both 0.75 and 1.5 g/kg alcohol significantly enhanced the behavioral response to PPI in adolescent, but not in adult rats. During prepulse + pulse trials, 1.5 g/kg alcohol significantly increased the N10 pulse response in the adolescent frontal cortex. Acute alcohol (0.75 and 1.5 g/kg) also increased the N1 ERP pulse response to prepulse stimuli in frontal and parietal cortices in adult rats, but not in adolescent rats. CONCLUSIONS: These data suggest that alcohol's effect on behavioral and electrophysiological indices of AS do not differ between adults and adolescents whereas developmental stage does appear to significantly modify alcohol-influenced response to PPI.

The alcoholic lung disease: historical background and clinical features.

SUMMARY: The purpose of this review article is to prove the damage that alcohol causes to the respiratory system. We will make a brief review of alcohols history in the course of the centuries till nowadays. The problem of addiction to alcohol (alcoholism) will be examined for several countries. Alcohol's metabolism is another topic to be discussed parallel to its pharmacological action. In addition, alcohol's impact on the respiratory system varies from damaging the mucociliary system to the regulation of breathing and from the sleep apnea syndrome to diffusion disorders. "Alcoholic lung disease" constitutes a syndrome despite the fact that the damage of the lung due to concurrent smoking and drug use is often indistinguishable.

Chemical colitis.

Chemical colitis can occur as a result of accidental contamination of endoscopes or by intentional or accidental administration of enemas containing various chemicals. Most cases have occurred after accidental contamination of endoscopes with glutaraldehyde and/or hydrogen peroxide. There have been multiple case reports of chemical colitis resulting from unintentional administration of caustic chemicals. Intentional administration of corrosive enemas has been implicated in sexual practices, bowel cleansing, or in suicide attempts. Patients present with nonspecific symptoms including abdominal pain, rectal bleeding, and/or diarrhea. As chemical colitis remains rare, the literature consists of scattered case reports and small series. Agents implicated in chemical colitis that are covered in this review include alcohol, radiocontrast agents, glutaraldehyde, formalin, ergotamine, hydrofluoric acid, sulfuric acid, acetic acid, ammonia, soap, sodium hydroxide, hydrogen peroxide, herbal medicines, chloro-m-xylenol, and potassium permanganate. Clinical, endoscopic, and histologic features are outlined for each agent in addition to the existing literature. Given the nonspecific presentation of many cases of chemically induced colitis, the diagnosis can be challenging if the pertinent history is not obtained. Most patients demonstrate the resolution of chemical-induced colitis after conservative or medical therapy. Depending on the depth and extent of injury, patients rarely require colectomy for ischemic colitis and/or peritonitis. Other postingestion complications include colonic strictures and rectovaginal fistulae. The benefits of medical therapy compared with conservative therapy are not known, as comparative clinical management trials have not been performed.

Preparation of corn (Zea mays) peptides and their protective effect against alcohol-induced acute hepatic injury in NH mice.

CPS [corn (Zea mays) peptides] were prepared from corn gluten meal by proteolysis with alcalase, an alkaline protease. The molecular-mass distribution of CPS is from 200 to 1000 Da as determined by MS. The amino acid composition of CPS was also analysed by HPLC. CPS contains almost no free amino acids. The protective effect of CPS against acute hepatic injuries induced by alcohol was verified in NH mice that were fed with different dosages of CPS for 30 days and subsequently given an acute dose of alcohol orally. As a result, CPS reduced both hepatic malondialdehyde and triacylglycerol levels, along with enhanced hepatic GSH (glutathione) levels, relative to the control. Hepatic histological changes were also observed. The result indicates that CPS is capable of attenuating ethanol-induced hepatic injury. The effect of CPS on removing superoxide anion in vitro was also studied as an additional proof that CPS is capable of abating hepatic superoxidant stress.

Fatal poisoning in methadone and buprenorphine treated patients -- are there differences?

BACKGROUND: Some recent studies have suggested a lower risk of fatal intoxications in drug-dependent patients under buprenorphine compared to methadone treatment. METHODS: Epidemiological reference data for the Munich region suggest that in 2003 approximately 10 % of all substitution patients were treated with buprenorphine, and 87 % with methadone. We studied the proportion of patients under methadone and buprenorphine substitution among drug-related deaths. Data from forensic post-mortem and toxicological analysis were analyzed. RESULTS: Data indicate that in 96 (35 %) of all 272 so-called drug deaths, methadone was involved compared to a single case of buprenorphine, possibly indicating a relatively better risk profile of buprenorphine. DISCUSSION: More prospective studies are necessary to assess the risk of fatal intoxications under different substitution regimens.

Spirituality, mindfulness and substance abuse.

A growing body of research suggests that mindfulness-based therapies may be effective in treating a variety of disorders including stress, chronic pain, depression and anxiety. However, there are few valid and reliable measures of mindfulness. Furthermore, mindfulness is often thought to be related to spirituality, given its roots in Buddhist tradition, but empirical studies on this relationship are difficult to find. The present study: (1) tested the reliability and validity of a new mindfulness measure, the Freiburg Mindfulness Inventory (FMI), (2) explored the relationship between mindfulness and spirituality, and (3) investigated the relationship between mindfulness and/or spirituality and alcohol and tobacco use in an undergraduate college population (N=196). Results support the reliability of the FMI and suggest that spirituality and mindfulness may be separate constructs. In addition, smoking and frequent binge-drinking were negatively correlated with spirituality scores; as spirituality scores increased the use of alcohol and tobacco decreased. Thus, spirituality may be related to decreased substance use. In contrast, a positive relationship between mindfulness and smoking/frequent binge-drinking behavior was uncovered, and warrants further investigation.

Pyridoxine in clinical toxicology: a review.

Pyridoxine (vitamin B6) is a co-factor in many enzymatic pathways involved in amino acid metabolism: the main biologically active form is pyridoxal 5-phosphate. Pyridoxine has been used as an antidote in acute intoxications, including isoniazid overdose, Gyromitra mushroom or false morrel (monomethylhydrazine) poisoning and hydrazine exposure. It is also recommended as a co-factor to improve the conversion of glyoxylic acid into glycine in ethylene glycol poisoning. Other indications are recommended by some sources (for example crimidine poisoning, zipeprol and theophylline-induced seizures, adjunct to d-penicillamine chelation), without significant supporting data. The value of pyridoxine or its congener metadoxine as an agent for hastening ethanol metabolism or improving vigilance in acute alcohol intoxication is controversial. This paper reviews the various indications of pyridoxine in clinical toxicology and the supporting literature. The potential adverse effects of excessive pyridoxine dosage will also be summarized.

Changes in electric charge and phospholipids composition in erythrocyte membrane of ethanol--poisoned rats after administration of teas.

Erythrocyte membrane components and electric charge can be modified by ethanol and by compounds formed as a result of its metabolism, particularly be reactive oxygen species (ROS). The effects of ROS can be neutralized by administering preparations with antioxidant properties. The natural preparations of this kind are teas. For this reason, it has been the purpose of this work to determine effect of green and black tea on membrane electric charge and phospholipids composition of an erythrocyte membrane from rats intoxicated with ethanol. Electrophoresis technique and HPLC have been applied to the above-mentioned studies. Ethanol administration caused an increase in erythrocyte surface charge density and phospholipids composition in the membrane. Administration of green and black tea with ethanol to the rats partially neutralizes the changes provoked by ethanol, and the action of green tea was stronger than that of black tea.