Alcohol Withdrawal Syndrome: Outpatient Management.

Approximately one-half of patients with alcohol use disorder who abruptly stop or reduce their alcohol use will develop signs or symptoms of alcohol withdrawal syndrome. The syndrome is due to overactivity of the central and autonomic nervous systems, leading to tremors, insomnia, nausea and vomiting, hallucinations, anxiety, and agitation. If untreated or inadequately treated, withdrawal can progress to generalized tonic-clonic seizures, delirium tremens, and death. The three-question Alcohol Use Disorders Identification Test-Consumption and the Single Alcohol Screening Question instrument have the best accuracy for assessing unhealthy alcohol use in adults 18 years and older. Two commonly used tools to assess withdrawal symptoms are the Clinical Institute Withdrawal Assessment for Alcohol Scale, Revised, and the Short Alcohol Withdrawal Scale. Patients with mild to moderate withdrawal symptoms without additional risk factors for developing severe or complicated withdrawal should be treated as outpatients when possible. Ambulatory withdrawal treatment should include supportive care and pharmacotherapy as appropriate. Mild symptoms can be treated with carbamazepine or gabapentin. Benzodiazepines are first-line therapy for moderate to severe symptoms, with carbamazepine and gabapentin as potential adjunctive or alternative therapies. Physicians should monitor outpatients with alcohol withdrawal syndrome daily for up to five days after their last drink to verify symptom improvement and to evaluate the need for additional treatment. Primary care physicians should offer to initiate long-term treatment for alcohol use disorder, including pharmacotherapy, in addition to withdrawal management.

Carnitine in Alcohol Use Disorders: A Scoping Review.

Recent studies in alcohol use disorders (AUDs) have demonstrated some connections between carnitine metabolism and the pathophysiology of the disease. In this scoping review, we aimed to collate and examine existing research available on carnitine metabolism and AUDs and develop hypotheses surrounding the role carnitine may play in AUD. A scoping review method was used to search electronic databases in September 2019. The database search terms used included "alcohol, alcoholism, alcohol abuse, alcohol consumption, alcohol drinking patterns, alcohol-induced disorders, alcoholic intoxication, alcohol-related disorders, binge drinking, Wernicke encephalopathy, acylcarnitine, acetyl-l-carnitine, acetylcarnitine, carnitine and palmitoylcarnitine." The inclusion criteria included English language, human-based, AUD diagnosis and measured blood or tissue carnitine or used carnitine as a treatment. Of 586 studies that were identified and screened, 65 underwent abstract review, and 41 were fully reviewed. Eighteen studies were ultimately included for analysis. Data were summarized in an electronic data extraction form. We found that there is limited literature available. Alcohol use appears to impact carnitine metabolism, most clearly in the setting of alcoholic cirrhosis. Six studies found carnitine to be increased in AUD, of which 5 were conducted in patients with alcoholic cirrhosis. Only 3 placebo-controlled trials were identified and provide some support for the use of carnitine in AUD to decrease cravings, anhedonia, and withdrawal and improve cognition. The increase in plasma carnitine in alcoholic cirrhosis may be related to disordered fatty acid metabolism and oxidative stress that occurs in AUD. The multiple possible therapeutic effects carnitine could have on ethanol metabolism and the early evidence available for carnitine supplementation as a treatment for AUD provide a foundation for future randomized control trials of carnitine for treating AUD.

Effect of Pingan Fang, a Traditional Chinese Medicine compound, on behavioral sensitization and conditioned place preference induced by ethanol in mice.

OBJECTIVE: To observe the effect of Pingan Fang (PG) on behavioral sensitization and conditioned place preference (CPP) induced by ethanol in mice, and to determine the intervention mechanism of PG on alcohol addiction. METHODS: A behavioral sensitization mouse model induced by ethanol was established to observe the effect of PG on the development and expression of behavioral sensitization induced by ethanol by recording the spontaneous activity of mice. The resident time of mice in a white box was measured to evaluate the effect of PG on developing CPP induced by ethanol. Concentrations of dopamine (DA), Glutamate (Glu), and ã-aminobutyric acid (GABA) in the corresponding mesolimbic region of mice were determined by enzyme-linked immunosorbent assay. RESULTS: Although PG did not alter spontaneous activity in mice, it reduced the growth of spontaneous activity stimulated by ethanol. The residence time in the white box after-ethanol-training of mice in CPP experiments was decreased. CONCLUSION: Our data suggested that PG blocked the development and expression of behavioral sensitization induced by ethanol and the development of CPP in mice. The mechanism might be related to the decreased content of DA and Glu and increased content of GABA in the mesolimbic dopamine system. This suggests that PG might be useful for the prevention and treatment of alcohol addiction.

Factors Affecting Ethanol-Induced Conditioned Place Preference and Locomotor Sensitization in Mice.

The rewarding effects of alcohol can lead to progressively heavier and more frequent drinking. Since studies of reward have mainly focused on responses to higher alcohol doses, the relations between reward and moderate/sustained alcohol exposure remain unknown. Our objective was to evaluate factors affecting the reward value of low alcohol doses and risk factors for increasing alcohol doses due to reward progression caused by alcohol exposure patterns. We thus performed conditioned place preference (CPP) and ethanol (EtOH)-induced locomotor sensitization tests in mice. Low-dose EtOH (0.5 or 1 g/kg twice/week)-induced CPP was stronger than that produced by saline control treatment, but the effect decreased with increasing numbers of conditioning trials. Moderate-dose/long-term EtOH exposure induced a weaker CPP than high-dose/short-term EtOH (2 g/kg twice/week) exposure with the same total EtOH dose (8 g/kg/experiment). Acamprosate calcium, an anti-relapse drug, preclusively reduced EtOH-induced CPP. EtOH induced CPP and locomotor sensitization in black but not white chamber, although the initial preference and the basal locomotion in each chamber were equal. Therefore the brightness of the chamber had an effect on EtOH-induced sensitization. Moreover, additional studies indicated that EtOH-induced locomotor sensitization also depends on the dose but not the administration interval. Paired associative learning with EtOH exposure is a potent factor influencing the level of reward produced by EtOH. Moreover, exposure to high doses of alcohol, even on an intermittent schedule, carries a higher risk of addiction than exposure to moderate doses over longer periods.

Prenatal ethanol exposure stimulates neurogenesis in hypothalamic and limbic peptide systems: possible mechanism for offspring ethanol overconsumption.

Exposure to ethanol during the prenatal period contributes to increased alcohol consumption and preference in rodents and increased risk for alcoholism in humans. With studies in adult animals showing the orexigenic peptides, enkephalin (ENK), galanin (GAL) and orexin (OX), to stimulate ethanol consumption, the question addressed here is whether prenatal ethanol alters the development in utero of specific neurons that express these peptides. With reports describing suppressive effects of high doses of ethanol, we examined the offspring of dams gavaged from embryonic day 9 to parturition with a control solution or lower ethanol doses, 1 and 3g/kg/day, known to promote ethanol consumption in the offspring. To understand underlying mechanisms, measurements were taken in postnatal offspring of the expression of ENK in the hypothalamic paraventricular nucleus (PVN) and nucleus accumbens (NAc), GAL in the PVN, and OX in the perifornical lateral hypothalamus (PFLH) using real-time qPCR and in situ hybridization, and also of the cell proliferation marker, 5-bromo-2-deoxyuridine (BrdU), and its double-labeling with either neuronal nuclei (NeuN), a marker of mature neurons, or the peptides. On postnatal day 15 (P15), after two weeks without ethanol, the offspring showed increased expression of ENK in the PVN and NAc core but not shell, GAL in the PVN, and OX in the PFLH. In these same areas, prenatal ethanol compared to control increased the density at birth (P0) of neurons expressing these peptides and at P0 and P15 of neurons double-labeling BrdU and NeuN, indicating increased neurogenesis. These BrdU-positive neurons were found to express ENK, GAL and OX, indicating that prenatal ethanol promotes neurogenesis in these specific peptide systems. There were no changes in gliogenesis or apoptosis. This increase in neurogenesis and density of peptide-expressing neurons suggests the involvement of these hypothalamic and accumbal peptide systems in mediating the increased alcohol consumption observed in prenatal ethanol-exposed offspring.

Alcoholism, personality, and religion/spirituality: an integrative review.

A review of the literature on the relationships between alcoholism, personality, and religion identified patterns that may help explain the inverse association between alcoholism and religion/spirituality (R/S). Personality plays a central role in two etiological models of alcoholism. The personality traits of high behavioral undercontrol (low Agreeableness and low Conscientiousness) and high negative affect (high Neuroticism) are both significantly related to higher alcohol use. Religiosity is also correlated with these traits, but in the opposite direction (e.g., with low behavioral undercontrol and low negative affect). Thus, the personality profiles associated with alcoholism and religion are the inverse of one another. In addition, evidence suggests that R/S moderates genetic variation on both Neuroticism and Disinhibition (part of behavioral undercontrol). Implications are discussed in terms of competing explanatory models: a basic research model which argues for genetically-determined stability in personality and alcoholism risk, and a clinical treatment model which argues for the primacy of environmental interventions in treatment and the possibility of personality change as a pathway to recovery.

Neurobiological mechanisms contributing to alcohol-stress-anxiety interactions.

This article summarizes the proceedings of a symposium that was presented at a conference entitled "Alcoholism and Stress: A Framework for Future Treatment Strategies." The conference was held in Volterra, Italy on May 6-9, 2008 and this symposium was chaired by Jeff L. Weiner. The overall goal of this session was to review recent findings that may shed new light on the neurobiological mechanisms that underlie the complex relationships between stress, anxiety, and alcoholism. Dr. Danny Winder described a novel interaction between D1 receptor activation and the corticotrophin-releasing factor (CRF) system that leads to an increase in glutamatergic synaptic transmission in the bed nucleus of the stria terminalis. Dr. Marisa Roberto presented recent data describing how protein kinase C epsilon, ethanol, and CRF interact to alter GABAergic inhibition in the central nucleus of the amygdala. Dr. Jeff Weiner presented recent advances in our understanding of inhibitory circuitry within the basolateral amygdala (BLA) and how acute ethanol exposure enhances GABAergic inhibition in these pathways. Finally, Dr. Brian McCool discussed recent findings on complementary glutamatergic and GABAergic adaptations to chronic ethanol exposure and withdrawal in the BLA. Collectively, these investigators have identified novel mechanisms through which neurotransmitter and neuropeptide systems interact to modulate synaptic activity in stress and anxiety circuits. Their studies have also begun to describe how acute and chronic ethanol exposure influence excitatory and inhibitory synaptic communication in these pathways. These findings point toward a number of novel neurobiological targets that may prove useful for the development of more effective treatment strategies for alcohol use disorders.

[Meaning of life in wives of alcoholics: autobiographical method].

PURPOSE: The purpose of this study was to explore and describe life-stories and meanings of life in wives of alcoholics by analyzing their autobiographies. METHODS: Autobiographies were collected from 20 participants who produced their own autobiographies in the logotherapeutic autobiography program at community alcohol counseling centers in Korea. The data were coded to identify themes of agency and communion using the manual coding system developed by McAdams, and analyzed by the existential approach. RESULTS: There were 214 coded episodes in twenty autobiographies. There were 128 agency themes and 86 communion themes. The most common themes were Love/Friendship. Five themes emerged from the autobiographical episodes on the existential perspective: 1) overcoming the suffering, 2) meaningful people and relationships, 3) spiritual maturation, 4) caring and helping, and 5) finding a meaning of life. CONCLUSION: These results showed that the wives of alcoholics who participated in the logotherapeutic autobiography program found the meaning of life through their suffering. Furthermore, a study on existential nursing interventions for people who have meaninglessness in life needs to be done.

Meaning of Life in Wives of Alcoholics: Autobiographical Method

PURPOSE: The purpose of this study was to explore and describe life-stories and meanings of life in wives of alcoholics by analyzing their autobiographies. METHODS: Autobiographies were collected from 20 participants who produced their own autobiographies in the logotherapeutic autobiography program at community alcohol counseling centers in Korea. The data were coded to identify themes of agency and communion using the manual coding system developed by McAdams, and analyzed by the existential approach. RESULTS: There were 214 coded episodes in twenty autobiographies. There were 128 agency themes and 86 communion themes. The most common themes were Love/Friendship. Five themes emerged from the autobiographical episodes on the existential perspective: 1) overcoming the suffering, 2) meaningful people and relationships, 3) spiritual maturation, 4) caring and helping, and 5) finding a meaning of life. CONCLUSION: These results showed that the wives of alcoholics who participated in the logotherapeutic autobiography program found the meaning of life through their suffering. Furthermore, a study on existential nursing interventions for people who have meaninglessness in life needs to be done.

Mechanisms of alcohol-associated cancers: introduction and summary of the symposium.

Chronic alcohol consumption is associated with an increased risk for cancers of many organs, such as oral cavity, pharynx, larynx, and esophagus; breast; liver; ovary; colon; rectum; stomach; and pancreas. An understanding of the underlying mechanisms by which chronic alcohol consumption promotes carcinogenesis is important for development of appropriate strategies for prevention and treatment of alcohol-associated cancers. The National Institute on Alcohol Abuse and Alcoholism, Office of Dietary Supplements, Office of Rare Diseases, National Cancer Institute, National Institute on Drug Abuse, and National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, sponsored an international symposium on Mechanisms of Alcohol-Associated Cancers in Bethesda, Maryland, USA, October 2004. The following is a summary of the symposium. Chronic ethanol consumption may promote carcinogenesis by (1) production of acetaldehyde, which is a weak mutagen and carcinogen; (2) induction of cytochrome P450 2E1 and associated oxidative stress and conversion of procarcinogens to carcinogens; (3) depletion of S-adenosylmethionine and, consequently, induction of global DNA hypomethylation; (4) induction of increased production of inhibitory guanine nucleotide regulatory proteins and components of extracellular signal-regulated kinase-mitogen-activated protein kinase signaling; (5) accumulation of iron and associated oxidative stress; (6) inactivation of the tumor suppressor gene BRCA1 and increased estrogen responsiveness (primarily in breast); and (7) impairment of retinoic acid metabolism. Nicotine may promote carcinogenesis through activation of extracellular signal-regulated kinase/cyclooxygenase-2/vascular endothelial growth factor signaling pathway.

Correlates of illicit drug use in Karen villages in Northern Thailand.

A study was conducted in 31 Karen tribal villages in Northern Thailand in 1999-2000 to address the question of why some villages have a relatively high prevalence of illicit drug use compared with others? Data were gathered from village leaders, residents, and through observations by field workers and the researchers, and included demographic, economic, and infrastructure development, and social and acculturation measures. Overall, few village-level variables were related significantly to drug use in the villages; those that were included: 1) better access to elementary education reported by "high drug" villages (81%) in comparison with "low drug" villages (29%) and 2) high drug villages reported having more alcoholic residents than low drug villages. The findings provide some support for the hypothesis that illicit drug use is positively associated with socioeconomic development, acculturation, and socialization into mainstream attitudes, values, and behaviors.

Papel de la neuropsicología en el alcoholismo / Role of neuropsychology in alcoholism

No disponible

Patterns of gene expression are altered in the frontal and motor cortices of human alcoholics.

Alcoholism is a major health problem in Western countries, yet relatively little is known about the mechanisms by which chronic alcohol abuse causes the pathologic changes associated with the disease. It is likely that chronic alcoholism affects a number of signaling cascades and transcription factors, which in turn result in distinct gene expression patterns. These patterns are difficult to detect by traditional experiments measuring a few mRNAs at a time, but are well suited to microarray analyses. We used cDNA microarrays to analyze expression of approximately 10 000 genes in the frontal and motor cortices of three groups of chronic alcoholic and matched control cases. A functional hierarchy was devised for classification of brain genes and the resulting groups were compared based on differential expression. Comparison of gene expression patterns in these brain regions revealed a selective reprogramming of gene expression in distinct functional groups. The most pronounced differences were found in myelin-related genes and genes involved in protein trafficking. Significant changes in the expression of known alcohol-responsive genes, and genes involved in calcium, cAMP, and thyroid signaling pathways were also identified. These results suggest that multiple pathways may be important for neuropathology and altered neuronal function observed in alcoholism.

Preclinical models to evaluate potential pharmacotherapeutic agents in treating alcoholism and studying the neuropharmacological bases of ethanol-seeking behaviors in rats.

The unit outlines four basic protocols designed to systematically evaluate the capacity of potential pharmacotherapeutic agents to effectively treat alcohol addiction and dependence in rats. Also included are procedures designed to study the neural mechanisms regulating alcohol-seeking behaviors.

1,8-cineol, a food flavoring agent, prevents ethanol-induced gastric injury in rats.

This study investigated the gastroptrotective effect of 1,8-cineole (cineole) on ethanol-induced gastric mucosal damage in rats and the possible mechanisms involved. 1,8-Cineole (50-200 mg/kg), given orally 1 hr before administration of 1 ml of absolute ethanol significantly attenuated the ethanol-induced gastric injury in a manner similar to nordihydroguairetic acid, a known lipoxygenase inhibitor. 1,8-Cineole showed a tendency to restore the ethanol-associated decreases in nonprotein sulfhydryls, suggesting a possible antioxidant effect. In gastric secretion studies, 1,8-cineole, similar to cimetidine, a known histamine-2 receptor antagonist, demonstrated significant inhibitions of both gastric juice volume as well as total acid output. The protection offered by 1,8-cineole was found to be unaltered by 8-phenyltheophylline or L-NAME, indicating that its effect is not mediated by endogenous adenosine or nitric oxide. These results, taken together with the earlier reports, suggest that the antioxidant and lipoxygenase inhibitory actions of 1,8-cineole are of prime importance in affording gastroprotection against ethanol injury in the rat.

Hallazgos en tomografía computarizada de la gangrena de Fournier / Computed Tomography findings in Fournier's gangrene

Objetivo: Describir la utilidad de la tomografía computarizada (TC) como método de imagen para identificar la gangrena de Fournier (GF) así como para estudiar la extensión de la misma.Material y métodos: Presentamos seis pacientes con el diagnóstico clínico de gangrena de Fournier. Se realizó TC con contraste oral e intravenoso (i.v.) en todos los pacientes.Resultados: En los seis casos existía masa de partes blandas y gas en la región escrotal y en cinco en la zona perineal. En dos pacientes existía gas que se extendía hacia la pared abdominal anterior y en uno de ellos aparecía en el espacio pararrenal anterior y posterior. Los factores predisponentes más importantes fueron la diabetes y el alcoholismo y el factor desencadenante más frecuente fue la patología urológica.Conclusión: La TC confirma la existencia de enfermedad, valora la extensión de la misma y en algunos casos permite identificar la causa del proceso (AU)

Psychological stress, drug-related cues and cocaine craving.

RATIONALE: While several environmental situations may produce cocaine craving, there is little research on whether patterns of drug cue reactivity are similar across different environmental situations. OBJECTIVE: This study examined whether two different environmental situations, psychological stress and drug cues, produce similar or varying patterns of cue reactivity in 20 cocaine dependent individuals. METHODS: All subjects participated in a single laboratory session and were exposed to stress, drug cues and neutral-relaxing imagery conditions. Cocaine and alcohol craving, emotion state ratings, subjective anxiety, heart rate and salivary cortisol measures were assessed. RESULTS: Significant increases in cocaine and alcohol craving were observed with stress and drug cues imagery but not with neutral-relaxing imagery. In addition, stress and drug cues situations produced similar increases in subjective anxiety, heart rate and salivary cortisol levels. Significant increases in negative emotion ratings and decreases in positive emotion ratings were found for stress and drug cues conditions as compared to the neutral condition. CONCLUSIONS: The findings indicate that a similar and comparable pattern of cue reactivity is induced by stress and drug cue manipulations. Furthermore, the comparable increases in subjective anxiety and negative affect observed with stress-induced and drug cue-induced craving provides support for the negative reinforcement model of drug craving and relapse. The negative affectivity co-occurring with the craving state appears to be an important target in the development of new treatments for cocaine dependence.

[The functional-morphological characteristics of alcohol-induced pathology as dependent on the nature of the intoxication and its nootropil correction in an experiment]. / Funktsional'no-morfologicheskie osobennosti alkogol'obuslovlennoi patologii v zavisimosti ot kharaktera intoksikatsii i korrektsii nootropiloim v éksperimente.

The response of hematological system, carbohydrate metabolism and pathomorphologic alterations in the viscera were studied for four weeks on the model of chronic alcoholization in conditions of hydrolytic alcohol production. It is shown that maximal deviations of all the parameters in white conventional rats occur after receiving a combined ethanol dose in inhalation of a mixture of methanol and furfurol vapour. Less manifest pathology was revealed in simultaneous introduction of nootropil solution. Thus, functional-morphologic changes in alcoholic intoxication in unfavourable environment are reversible in purposeful application of drugs with neurometabolic effect.

[Effect of acetaldehyde on the formation of alcohol dependence in animal experiments]. / Vliianie atsetal'degida na formirovanie alkogol'noi zavisimosti v éksperimentakh na zhivotnykh.

As a result of the experiment on the laboratory animals under the continuous administration of acetaldehyde there has been revealed the latter as inducing the aldehyde dehydrogenase activity in the cytosol fraction of the cerebral structures/hypothalamus, mid-brain and new cerebrum cortex/as well as in the levels of biogenic amines/noradrenaline and 5-hydroxytryptamine/in the same structures while forming experimentally in the laboratory animals the alcoholic dependence under acetaldehyde alcoholic dependence. The work displays some changes of alcohol dehydrogenase and action.