Nihon Arukoru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence最新文献

Vascular function is regulated by a balance of vasoconstriction and vasorelaxation. Disorder in this balance due to alcohol consumption causes various clinical conditions. In this review, we discuss the effects of acute and chronic ethanol consumption on vascular responses, including vasoconstriction, endothelium-dependent vasorelaxation, and nerve-mediated vasorelaxation. Acute ethanol administration induces vasoconstriction in ethanol-naive animals in vitro. Furthermore, ethanol can both potentiate and suppress agonist-induced Ca(2+)-dependent vasoconstriction. Moreover, ethanol augments Ca(2+)-independent vasoconstriction by increasing Ca2+ sensitivity. Endothelium-dependent relaxation is mediated by the nitric oxide (NO) pathway and the endothelium-derived hyperpolarizing factor (EDHF) pathway. Acute ethanol treatment inhibits both NO- and EDHF-mediated relaxation. Furthermore, acute ethanol ingestion can also potentiate and suppress calcitonin gene-related peptide (CGRP)-induced nerve-mediated relaxation. These opposing effects may be due to differences in species or vascular beds. Thus, acute ethanol treatment decreases vasorelaxation, thereby shifting the contraction-relaxation balance towards contraction. Combined, these effects are one mechanism by which acute heavy alcohol consumption causes circulatory disturbances such as vasospasms or ischemic heart disease. In contrast, chronic low-dose ethanol has no effect on vasoconstriction, whereas chronic high-dose ethanol increases vasoconstriction. Additionally, chronic ethanol intake has diminished, unchanged, and even increased effects on nerve-mediated relaxation; therefore, conclusions on these effects are not possible at present. Interestingly, chronic low-dose ethanol administration enhanced endothelium-dependent relaxation; however, higher doses inhibited these responses. Therefore, regular or light-to-moderate alcohol intake increases vasorelaxation and may suppress elevated blood pressure, whereas chronic heavy alcohol consumption may raise blood pressure, causing various clinical conditions.

Nicotine dependence and its neural mechanisms have been well documented by pharmacological, behavioral and neuroscience studies. In this review, we introduce recent new findings in this theme, particularly on the role of nicotine -associated stimuli as non-pharmacological factors affecting maintaining/reinstating nicotine seeking. By using the techniques of drug self-administration and conditioned place preference, nicotine's specific property of forming seeking/taking behavior is well characterized, and the mechanisms of seeking/taking could be partly explained by discrete and/or contextual conditioned stimuli (dCS and cCS). After having the repeated Pavlovian conditioning in the training/conditioning sessions, CSs begin to play a key role for eliciting nicotine seeking behavior, with the activation of mesolimbic dopaminergic systems. In our study, intracranial self- stimulation (ICSS) was used to assess the mesolimbic dopamine activity. The nicotine-associated cCS also activated this neural system, which resulted in decreasing the ICSS threshold approximately 20% in the testing session under the cCS presentation. This finding would support the evidence of CS-induced incentive motivation for nicotine. According to the incentive salience hypothesis, the mesolimbic dopamine reflects the motivation elicited by incentives (CSs), and induces the drug seeking behavior, which is activated through amygdala--nucleus accumbens--medial prefrontal cortex circuit. Additionally, human brain imaging studies have revealed that tobacco- associated stimuli activate not only these regions, but also right temporo-parietal junction of human cortex, which is relevant to the visual attention. In summary, the above evidence shows that nicotine-conditioned stimuli might have powerful incentive salience and regulate nicotine seeking/taking behavior in animals and humans, though stress and nicotine-withdrawal could also enhance nicotine taking in the same way as other dependence -producing mechanisms.

A survey of 21,493 patients who visited our Health Check-up Center during the 6-year period from 2005 to 2010 was conducted for the endpoints of drinking situation and various lifestyle-related diseases. Males accounted for 57.2% (mean age: 53.2 ± 11.4) and females accounted for 42.8% (mean age: 52.5 ± 11.4) of patients surveyed. Patients with no drinking habit accounted for 24.8% and 62.9% of males and females, respectively, and a large gender difference was seen in drinking frequency. When examined by age group, drinking frequency was found to increase with age in males, but gradually decreased with age in females. An examination of alcohol consumption in males revealed that 23.5% had an ethanol conversion rate of 10 g/day, 19.1% had a rate of < 20 g/day, and 18.2% had a rate of < 40 g/day. Meanwhile, in females, 22.7% had a rate of ≤ 10 g/day, 7.6% had a rate of ≤ 20 g/day and 4.6% had a rate of ≤ 40 g/day. The association between lifestyle-related disease endpoints and alcohol consumption was next examined by multivariate logistic analysis. The association between drinking and body mass index (BMI) revealed an odds ratio of around 0.8 in patients who consumed ≤ 40 g/day and a significantly reduced frequency of obesity. The odds ratio of hypertension increased in a dose-dependent manner from 1.3 to 1.6 in patients who consumed ≥ 40 g/day. The frequency of high low-density lipoprotein cholesterol (LDL-C) was reduced in light drinkers and the odds ratio decreased from 0.77 to about 0.6 as alcohol consumption increased: The frequency of low high-density lipoprotein cholesterol (HDL-C) was similarly reduced in light drinkers, and the odds ratio decreased remarkably in a dose-dependent manner from 0.73 to 0.22 as alcohol consumption increased. The risk of triglycerides was reduced in light drinkers and was conversely significantly enhanced in heavy drinkers. In patients who consumed ≥ 20 g/day, the risk of impaired glucose tolerance increased significantly in a dose-dependent manner. Increased risk of hyperuricemia was seen even in light drinkers. and the odds ratio increased from 1.2 to 1.8 as alcohol consumption increased. The results of this cross-sectional study suggested that light drinking has a positive effect on BMI, LDL-C, HDL-C and triglycerides. On the other hand, heavy drinking was found to have a positive effect on LDL-C and HDL-C, but a negative effect on systolic blood pressure, triglycerides, fasting blood glucose and uric acid.

We experienced a case showing various psychotic symptoms following cessation of alcohol consumption. The symptoms included depressive state, delusion, confusion, psychomotor excitement and delirium, all of which disappeared in about two months. At first, we regarded all the symptoms as alcoholic hallucinosis, by a clinical standpoint, in spite of no auditory hallucination in this case. However, taking the overall clinical course into consideration, withdrawal syndrome could have been affected by some factors. One of the possibilities is that delusion might have been induced by aripiprazole. There still may be some other unknown influential factors on withdrawal, which are indicated by previous papers.

Interleukin (IL)-1 β is a cytokine that is upregulated by the pro-inflammatory bacterial endotoxin lipopolysaccharide. This study examined the effect of ethanol on IL-1 β-mediated suppression of phenylephrine-induced contractility and inducible nitric oxide synthase (iNOS) expression in the rat superior mesenteric artery (SMA). IL-1 β suppressed the phenylephrine-induced contractile response, and this effect was inhibited by ethanol. The IL-1 β-mediated effects were also blocked by cycloheximide, an inhibitor of protein synthesis, as well as AMT and 1400W, which are iNOS inhibitors, and PTIO, an NO scavenger. However, indomethacin, a cyclooxygenase (COX) inhibitor that promotes NO-independent vasodilation, did not affect IL-1 β-mediated suppression of the contractile response. Western blot analysis revealed that iNOS levels in SMA were upregulated by IL-1 β and inhibited by ethanol (50 and 100 mM). These results indicate that the suppression of the SMA contractile response by IL-1 β requires iNOS activity, but not COX-2. Furthermore, these data suggest that ethanol inhibits the effects of IL-1 β on the contractile response via inhibition of iNOS, rather than COX-2.

Objectives: Alcohol consumption before bathing is listed as a risk factor for sudden death in a bathtub, which occurs relatively frequently in Japan. This study aimed to clarify the epidemiology of alcohol-related deaths in bathtubs.

Subjects: Among all autopsy cases that were performed at the Tokyo Medical Examiner's Office between 2009 and 2010 (N = 5635), 357 cases of death in a bathtub were evaluated. Data regarding age, sex, blood ethanol level, manner and. cause .of death, alcohol consumption, and alcohol-related gastrointestinal diseases were extracted. The cases were divided into three groups according to their blood ethanol levels (no blood ethanol, low ethanol, and high ethanol), and their data were compared.

Results: A large majority of the cases in all groups involved persons who were 50-89 years old. The mean age of the high ethanol group (61.7 years) was significantly lower than.that of the control group (71.1 years; P < 0.01). In addition, the proportion of men was significantly higher in the low and high ethanol groups (70.1% and 75.5%, respectively), compared to that in the control group (55.9%; P < 0.05). Daily alcohol consumption was significantly more common in the low and high ethanol groups (49.5% and 87.8%, respectively), compared to that in the control group (23.2%; P < 0.01). Furthermore, alcohol-related gastrointestinal diseases were more common in the low and high ethanol groups (26.8% and 63.3%, respectively), compared to that in the control group (4.3%; P < 0.01).

Conclusions: Preventive strategies for reducing alcohol-related deaths in bathtubs should target male habitual drinkers (middle-aged to seniors), especially patients who have been diagnosed with alcohol-related diseases.

Unlabelled: Serigaya Methamphetamine Relapse Prevention Program (SMARPP) is an effective treatment program for drug-dependent patients that has been introduced by many psychiatric institutions. To conduct SMARPP effectively, the issues accompanying this program need to be clarified. Recently, an investigation was conducted on the healthcare/medical institutions that introduced this program and the results are reported in this study.

Subjects: Of healthcare/medical institutions that have introduced SMARPP as of June 2012, 35 were selected as subjects.

Results and discussion: Responses were collected from 26 institutions. Responses were also collected from 165 healthcare professionals who have conducted SMARPP at the 26 institutions. About 35% of the institutions were not medical institutions specializing in treatment of drug dependence. Of the healthcare professionals who have conducted the program, 26.7% (n = 44) completed a SMARPP training course; with most of them having no opportunity to participate in a training course before conducting it. Forty-three percent of them (n = 71) conducted the program once a week. The staff in charge of SMARPP reported participants' troublesome words and actions that they confronted. There were 60 cases in which the staff found it difficult to answer the participant's question, 91 cases in which they found it difficult to respond to the participant's behavior, and 98 cases in which they found it difficult to lead the meeting. Most of these words and actions seemed to reflect .'resistance' that was recognized in the course of treatment of drug dependence/alcoholism. The 'resistance' can be categorized into the following two types: 'resistance' to staying away from drug/alcohol which is also called 'suction talk' and 'resistance' reflecting 'discord' in the treatment relationship. Because physicians and psychologists were generally in charge of meetings, they frequently found it difficult to cope with troublesome situations. More healthcare professionals with the experience of treatment of drug dependence/alcoholism recognized difficulty in coping with them. This is probably because, unlike the conventional treatment for dependence emphasizing guiding or educational aspect, SMARPP is an intervention focusing on raising awareness. As a method of intervention for the participants in SMARPP, the intervention that does not control patients' 'resistance,' characteristic of motivational interviewing, seems to be effective.

Inositol 1,4,5-trisphosphate receptors (IP3Rs) are classified to a multigene family of channel proteins that mediate Ca2+ release from endoplasmic reticulum, and are one of regulators to modify intracellular Ca2+ concentration. Little is known about functional relationship between rewarding effects due to drugs of abuse and IP3Rs. This report reviews the roles and regulatory mechanisms of intracellular Ca2+ channels, especially type 1 IP3Rs (IP3Rs-1), in brain of animals with rewarding effects produced by drugs of abuse. Our recent studies have reported that the blockade of IP3Rs suppresses the development of rewarding effects on methamphetamine or cocaine, suggesting that functional up-regulation of IP3R-1 occurs during the development of rewarding effects. Moreover, the critical expression of IP3R-1 in the development of methamphetamine- and cocaine-induced rewarding effects are regulated by Ca2+ participating in signal transduction pathways via both dopamine D1 and D2 receptors. Taken together these results it is suggested that the changes in IP3R-1 play an essential role in the development of drug dependence.

Coping skills training (CST) and cue exposure treatment (CET) have yielded favorable outcomes when used to treat alcoholics. We conducted 6-week inpatient programs that consisted of 9 CST group sessions (n = 117) during 2005-2009 and 9 CST group sessions plus 4 CET group sessions (n = 49) during 2009-2011 and subsequent 1-year letter therapy for Japanese alcoholic men who had relapsed and been readmitted after standard cognitive-behavioral inpatient therapy. When patients received a letter containing encouraging words every 2 weeks, they were asked to reread their CST and CET records and to respond to the letter by marking drinking days on a calendar and naming the skills on a list of the 9 CST themes and CET that were useful for maintaining abstinence during that 2-week period. The estimated percentages of achievement of 30 or fewer drinking days during the one year of letter therapy were 36.1 - 45.8%. 'Non-smoking', '2nd admission', and 'After age-limit job retirement' were significant factors in achieving good outcomes. The 'usefulness' responses for 'Increasing pleasant activities', 'CET', 'Anger management', ' Managing negative thinking', 'Problem solving', and ' Seemingly irrelevant decisions' as percentages of overall responses to the letters were significantly higher, in order of decreasing percentages, in the achiever group than in the non-achiever group, but the differences between the groups in ' Managing urges to drink', ' Drink refusal skills', ' Planning for emergencies', and ' Receiving criticism about drinking' were not significant. The odds ratios for achievement of 30 or fewer drinking days during the 1-year period increased significantly by 1.15 -1.31 fold per 10% increment in the 'usefulness' ratio for 'Increasing pleasant activities'. The difference in percentage achievement between the group treated by CST alone and the group treated by CST plus CET was not significant. In conclusion, some coping skills were more useful for relapse prevention than others in this study population, and addition of CET to CST and subsequent letter therapy did not improve outcomes.

Alcohol intake leads to the distribution of alcohol and its metabolite, acetaldehyde throughout the blood and organs. Hepatic cirrhosis is associated with abnormal red blood cell morphology and function, particularly impaired red blood cell deformability. To investigate the effect of drinking on red blood cells in patients with hepatic cirrhosis, erythrocyte deformability was evaluated in response to alcohol and acetaldehyde tolerance. Erythrocyte deformability in 10 healthy and 15 cirrhotic subjects was examined by filterability of the red blood cells. Erythrocyte deformability decreased markedly in the cirrhosis group compared with the healthy group (p < 0.05). No significant change in erythrocyte deformability was observed in healthy or cirrhotic subjects due to ethanol 100 mM tolerance. Acetaldehyde tolerance elicited a significant decrease in erythrocyte deformability at 2 mM in the cirrhosis group (p < 0.05). Alcohol consumption in cirrhotic patients was suggested to worsen erythrocyte deformability and red blood cell function. Decreased erythrocyte deformability worsens microcirculation in the liver, resulting in more severe hepatic dysfunction.