Validity and reliability of a driving simulator for evaluating the influence of medicinal drugs on driving performance.

RATIONALE: Although driving simulators (DS) are receiving increasing attention due to concern over traffic accidents under the influences of drugs, few DS are recognized for their reliability and validity. Therefore, the development of an evaluation system using DS for driving performance is urgently needed. OBJECTIVES: To investigate whether the standard deviation of lateral position (SDLP) increases with blood alcohol concentration (BAC) using a DS with reliability and calculate the SDLP threshold from the difference between BAC levels of 0 and 0.05%. METHODS: Twenty healthy Japanese men performed the DS tasks up to 60 min in Study 1 and DS tasks twice at 1-week intervals in Study 2. Twenty-six healthy men conducted the same DS tasks under BAC level (0, 0.025, 0.05, and 0.09%) in double-blind, randomized, crossover trial in Study 3. The primary outcome was SDLP in a road-tracking test. The test-retest reliability of DS data was assessed, and the estimated difference in SDLP between BAC levels of 0 and 0.05% was calculated using a linear regression model. RESULTS: The cumulative SDLP values at 5-min intervals were stable, and the intraclass correlation coefficient for its values was 0.93. SDLP increased with BAC in a concentration-dependent manner. The predicted ΔSDLP value for the difference between BAC levels of 0 and 0.05% was 9.23 cm. No participants dropped out because of simulator sickness. CONCLUSIONS: The new DS used in these studies has reliability, validity, and tolerability and is considered suitable for evaluating the influence of drugs on driving performance.

The Role of Cariporide in Protecting Saphenous Vein among Different Aldehyde Dehydrogenase Genotypes.

OBJECTIVE: We aimed to study the effect of cariporide (CP) on protecting the saphenous vein and the role of acetaldehyde dehydrogenase 2 (ALDH2) in coronary artery bypass grafting (CABG). BACKGROUND: The saphenous vein is the main graft material used in CABG. Recent studies suggested that CP is effective in protecting against various cardiovascular diseases. METHODS: Segments of a surgically removed saphenous vein were used to examine the vascular response to CP. The ALDH2 genotype and expression of related proteins were assessed by Western blotting and immunohistochemistry. RESULTS: Among the conditions tested, the University of Wisconsin solution with CP (4°C, 5 min) treatment showed the best protective effect on the saphenous vein. The incidence of major adverse cardiac events was higher in the ALDH2-GA (heterozygous mutant) genotype population after CABG. CONCLUSION: CP plays a role in reducing the production of reactive oxygen species and apoptosis by ALDH2-mediated mitochondrial function improvement. The ALDH2 mutant genotype might be one of the risk factors for coronary atherosclerotic heart disease.

Impacts of interactions between ADH1B and ALDH2 genotypes on alcohol flushing, alcohol reeking on the day after drinking, and age distribution in Japanese alcohol-dependent men.

OBJECTIVE: This study sought to evaluate the impacts of interactions between the alcohol dehydrogenase-1B (rs1229984) genotype and the aldehyde dehydrogenase-2 (rs671) genotype on alcohol flushing, alcohol reeking on the day after drinking, and the age distribution in alcohol-dependent patients. METHODS: The study subjects were 4107 Japanese alcohol-dependent men who underwent alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 genotyping: 4051 patients were asked about their current or former tendency to experience facial flushing after drinking a glass of beer, and 969 patients were asked about whether they had ever been told that they reeked of alcohol more than 12 hours after they had stopped drinking. RESULTS: Current, former, and never flushing were reported in 3.5, 14.9, and 81.5%, respectively, of the subject, and alcohol reeking after more than 12 hours in 36.1% of the subjects. The fast-metabolizing ADH1B*2(+) genotype (*1/*2 or *2/*2) and the inactive ALDH2*2(+) genotype (*1/*2 or *2/*2) affected the multivariate odds ratios for current or former flushing [odds ratio, 95% confidence interval = 2.27 (1.79-2.86) and 23.0 (18.6-28.5), respectively, vs. *2(-) genotype] and for alcohol reeking [0.39 (0.29-0.52) and 1.56 (1.09-2.25), respectively, vs. *2(-) genotype]. An age-dependent decrease in the ADH1B*2(-) and ALDH2*2(-) combination from 32.3% in the 30-39-year age group to 12.5% in the 70-79-year age group and an age-dependent increase in the ADH1B*2(+) and ALDH2*2(-) combination from 52.5% in the 30-39-year age group to 70.5% in the 70-79-year age group were observed (P < 0.0001 for trend). The frequencies of the ADH1B*2(-) and ALDH2*2(+) combination (4.7-6.2%) and the ADH1B*2(+) and ALDH2*2(+) combination (8.9-12.0%) did not change markedly with increasing age. CONCLUSION: Interactions between the alcohol dehydrogenase-1B and aldehyde dehydrogenase-2 genotypes modified alcohol flushing, alcohol reeking on the day after drinking, and the age distribution. These findings support the protective roles of the ADH1B*2(+) and ALDH2*2(+) genotypes against the development of alcohol dependence.

East Asian variant of aldehyde dehydrogenase 2 is related to worse cardioprotective results after coronary artery bypass grafting.

OBJECTIVES: Aldehyde dehydrogenase 2 activity is associated with cardioprotection. Individuals carrying an East Asian variant of the ALDH2 genotype (ALDH2*2) have significantly reduced aldehyde dehydrogenase 2 activity. No previous studies have determined the effect of the ALDH2*2 genotype on cardioprotective results after coronary artery bypass grafting (CABG). METHODS: In total, 207 patients who underwent selective off-pump CABG were prospectively enrolled. Their baseline characteristics and clinical results were collected. Preoperative and postoperative circulating oxidative stress levels (serum malondialdehyde adducts and hydroxynonenal adducts) were measured. After genotyping, the oxidative stress levels and clinical results were compared between the ALDH2*2 carriers and non-carriers. RESULTS: ALDH2*2 carriers exhibited higher levels of malondialdehyde (P = 0.02) and hydroxynonenal (P = 0.03) adducts after CABG. ALDH2*2 carriers had higher postoperative troponin I levels (P = 0.01) and 24-h inotropic scores (P = 0.02). The intensive care unit time (P = 0.03) and postoperative length of stay (P = 0.03) were longer in ALDH2*2 carriers. The postoperative pulmonary infection rate was higher (P = 0.03) in ALDH2*2 carriers. CONCLUSIONS: Patients with the ALDH2*2 genotype had higher postoperative oxidative stress levels and poorer clinical results after CABG. Special cardioprotective techniques should be considered for patients with a history of 'facial flushing' when performing CABG.

Adult-onset hypothyroidism increases ethanol consumption.

RATIONALE: Only in Europe it can be estimated that more than 20 million of people would be affected by hypothyroidism in some moment of their life. Given that ethanol consumption is so frequent, it would be reasonable to ask what the consequences of ethanol consumption in those individuals affected by hypothyroidism are. OBJECTIVES: To study the interaction between hypothyroidism and ethanol consumption. METHODS: We study ethanol consumption in a rat model of methyl-mercaptoimidazole-induced-adult-onset hypothyroidism and thyroid T4/T3 hormone supplementation. Also, we studied the effects of ethanol on motor activity, memory, and anxiety. RESULTS: We found that hypothyroidism increased the voluntary ethanol consumption and that this was enhanced by thyroid hormone supplementation. Hypothyroidism was associated with motor hyperactivity which was prevented either by T4/T3 supplementation or ethanol. The relationship between hypothyroidism, ethanol, and anxiety was more complex. In an anxiogenic context, hypothyroidism and T4/T3 supplementation would increase immobility, an anxiety-like behavior, while in a less anxiogenic context would decrease rearing, a behavior related to anxiety. Regarding memory, acute ethanol administration did not alter episodic-like memory in hypothyroid rats. Gene expression of enzymes involved in the metabolism of ethanol, i.e., Adh1 and Aldh2, were altered by hypothyroidism and T4/T3 supplementation. CONCLUSIONS: Our results suggest that hypothyroid patients would need personalized attention in terms of ethanol consumption. In addition, they point that it would be useful to embrace the thyroid axis in the study of ethanol addiction, including as a possible therapeutic target for the treatment of alcoholism and its comorbid disorders.

Autoantibody against aldehyde dehydrogenase 2 could be a biomarker to monitor progression of Graves' orbitopathy.

PURPOSE: This study surveyed the novel autoantigens expressed in the orbital fat tissue of patients with Graves' orbitopathy (GO) and explored the possibility of the autoantibodies against novel autoantigens as biomarkers for GO. METHODS: We used immuno-proteomic methods to survey novel autoantigens expressed in the orbit fat tissue of GO patients and confirmed by enzyme-linked immunosorbent assay (ELISA). RESULTS: One protein spot (aldehyde dehydrogenase 2 (ALDH2)) revealed high reactivity with the GO serum than did the healthy control serum and was further verified by ELISA. We found that the plasma anti-ALDH2 antibody level was increased in GO patients compared to healthy control donors. In addition, anti-ALDH2 antibody level was correlated with GO activity classified by clinical activity score(r = 0.588, p < 0.001, using Pearson's correlation). CONCLUSIONS: These increased levels of anti-ALDH2 antibody in GO serum suggested that ALDH2 could attribute target autoantigen in GO, and anti-ALDH2 autoantibody might serve as a biomarker for GO and help to predict disease activity.