Acute effects of resveratrol to enhance cocaine-induced dopamine neurotransmission in the striatum.

Resveratrol is known as an activator of SIRT1, which leads to the deacetylation of histone and non-histone protein substrates, but also has other pharmacological profiles such as the inhibition of monoamine oxidase (MAO)-A and MAO-B. Resveratrol was previously demonstrated to potentiate the rewarding effects of chronic cocaine via activation of SIRT1. However, the role of resveratrol in cocaine responses in the acute phase remains unexplored. Therefore, we investigated the acute effects of resveratrol on cocaine-stimulated dopamine neurotransmission by analyzing protein phosphorylation in neostriatal slices. Treatment with resveratrol (50µM for 30min) enhanced cocaine-induced increases in the phosphorylation of DARPP-32 at Thr34 and GluA1 at Ser845, postsynaptic substrates for dopamine/D1 receptor/PKA signaling, and a cocaine-induced decrease in the phosphorylation of tyrosine hydroxylase at Ser40, a presynaptic substrate for dopamine/D2 receptor signaling. The inhibition of both MAO-A and MAO-B by clorgyline and pargyline, respectively, enhanced the effects of cocaine on DARPP-32 phosphorylation. The acute effect of resveratrol on cocaine-induced DARPP-32 phosphorylation was occluded with inhibition of MAO-A and MAO-B. In behavioral studies, resveratrol (40mg/kg, s.c.) enhanced the increase in locomotor activity induced by acute cocaine administration (10mg/kg, i.p.). Thus, this study provides pharmacological evidence that acute resveratrol enhances cocaine-induced dopamine neurotransmission and behavioral responses, presumably via mechanisms involving the inhibition of dopamine catabolism by MAO-A and MAO-B. Resveratrol may be useful to treat dysregulated dopamine neurotransmission, but it may enhance the risk of developing drug addiction.

Factors for drop-out psychiatric treatment in patients with substance-related disorders.

We studied 199 inpatients and outpatients at a public psychiatric hospital to clarify the factors related to outcome following psychiatric care for substance-related disorder (SRD), and we discuss approaches for more effective community care in the future. The percentage of patients who discontinued treatment was 33.7%, suggesting that creation of a follow-up system for continuing outpatient care is an urgent task. Women were 35% more likely higher to discontinue treatment than men. Those with solvent dependence were 12% and 7.32 times more likely, respectively, to discontinue treatment than those with alcohol dependence. Those without complications were 2.24 times more likely than those with complications to discontinue treatment. Divorced patients were 18% and 6.35 times more likely, respectively, to discontinue treatment than married patients. There is insufficient support for patients with solvent dependence, and we observed that patients tended to have little motivation to stop using drugs or alcohol until physical complications occurred. Among the many divorced patients, desire for treatment was weak following breakdown of the family. The present findings suggest the importance of comprehensive efforts to treat substance use disorder at specialist medical institutions.

[Antibody titers against measles, rubella, mumps and varicella-zoster viruses in medical students].

It is important to identify and immunize susceptible students who have clinical practice to prevent and control hospital infections. The antibody titers to measles, rubella, mumps and varicella viruses were measured in 1,139 students(417 men, 722 women, average age 21.3+/-2.7 yr old)including 510 medical students, 442 nursing students and 187 students of the School of Medical Technology in Kurume University. Antibodies against measles virus were detected by particle agglutination assay(PA), those against rubella virus by hemagglutination inhibition assay(HI), and those against mumps and varicella viruses by enzyme-linked immunosorbent assay(EIA). The serological susceptibilities to measles, rubella, mumps and varicella viruses were 112(9.8%), 112(9.8%), 163(14.3%)and 73(6.4%), respectively. The serological susceptibilities to measles, rubella and mumps viruses in male students were not different from those in female students. The susceptibility to varicella virus in female students was significantly higher than that in male students. After susceptible students were recommended to have vaccinations against each virus, the vaccination rate of the students without antibody was 99.1%. The history of infection and vaccination against the viruses were examined by self-recorded questionnaires in 406 students from all disciplines. The serological susceptibility of students with positive vaccination history was 11.1% for measles, 6.8% for rubella, 18.3% for mumps, and 4.9% for varicella. The serological susceptibility of students with a positive infection history was 5.7% for measles, 3.4% for rubella, 2.9% for mumps, and 4.9% for varicella. In the self-recorded questionnaire, the rate of unknown infection and vaccination histories were 57.5% and 71.6% for measles, 52.5% and 68.4% for rubella, 34.3% and 75.6% for mumps, and 27.1% and 80.5% for varicella, respectively. In conclusion, these data confirm that it is essential to assess immune status against measles, rubella, mumps and varicella in students who have clinical practice in hospital regardless of infection or vaccination history. Accordingly, susceptible students should be vaccinated to prevent those viral infections in hospital.

Characteristic features of QRST integral mapping in patients with high risk Brugada syndrome.

BACKGROUND: The characteristic features of QRST integral mapping in the Brugada-type resting ECG of patients at a high risk for life-threatening ventricular arrhythmias were examined. METHODS AND RESULTS: QRST integral mapping was performed in 11 Brugada-type ECG patients with histories of aborted sudden death, spontaneous ventricular tachycardia and fibrillation (VT/VF) or programmed electric stimulation-inducible VT/VF (high risk group); 13 Brugada-type ECG patients without a history of such events (low risk group); and 21 age-matched healthy controls. Individual QRST isointegral maps revealed the minimum integral in the mid-to-right upper chest in 100% and 85% of the control and low risk groups, respectively, whereas this integral was 64% in the upper right back of the high risk group (p<0.05). On the QRST integral departure maps, the abnormal positive departure area (integral value>or=+2 standard deviation) was located in the mid-to-right upper chest in 82% and 8% of the high and low risk groups, respectively (p<0.05). During the follow-up period, sudden death or VF occurred in 4 of 6 high risk patients with both the abnormal findings. CONCLUSION: The abnormal positive departure area in the mid-to-right upper chest and the minimum QRST integral in the right upper back were distinct hallmarks for screening patients with the high risk Brugada-type ECG.

Very long chain N-3 fatty acids intake and carotid atherosclerosis: an epidemiological study evaluated by ultrasonography.

Epidemiological studies have shown an inverse relationship between intake of N-3 fatty acids and incidence of stroke. And, there is a high incidence of stroke in patients with carotid atherosclerosis. We investigated the relationship between intake of N-3 fatty acids and carotid atherosclerosis in the cross-sectional study. A total of 1920 Japanese, aged over 40 years, received a population-based health examination in 1999. They underwent B-mode carotid ultrasonography to evaluate the carotid intimal-medial thickness (IMT). Eating patterns were evaluated by a 105 items food frequency questionnaire. A complete data set was available for 1902 subjects (785 men and 1117 women). The mean eicosapentaenoic acid (EPA) intake in men was 0.32+/-0.23 g/day and in women was 0.31+/-0.20 g/day. The mean docosahexaenoic acid (DHA) intake in men was 0.52+/-0.34 g/day and in women was 0.49+/-0.29 g/day. With multiple linear regression analysis, after adjustments for age, sex, and total energy intake, intakes of EPA (P < 0.05), DHA (P < 0.05), and docosapentaenoic acid (P < 0.05) were significantly and inversely related to IMT. These data indicate that dietary N-3 fatty acid, especially very long chain N-3 fatty acids, may protect against carotid atherosclerosis.