Effect of ethanol on hepatotoxicity and hepatic DNA-binding of aflatoxin B1 in rats

The hepatocarcinogen aflatoxin B1 is converted to reactive metabolites that bind covalently to cellular macromolecules. These metabolites may also react with glutathione, resulting in the formation of glutathione conjugates and detoxication of the reactive metabolite. When rats were pretreated with ethanol by gastric intubation at a dose of 100 mmol/kg, 6 hr (the time of maximal GSH depletion) before the administration of aflatoxin B1, the covalent binding of 8,9-epoxide-aflatoxin B1 to DNA in vivo was increased by 47% and the hepatotoxicity was also potentiated. However, the covalent binding was not increased by pretreatment with ethanol 18 hr (time with approximately normal GSH levels) before administration of the toxin, and no potentiation of hepatotoxicity was observed. Pretreatment with a non-toxic dose of ethanol had no effects on the activity of glutathione S-transferase and glutathione peroxidase. These results suggest that the depletion of GSH and the increased formation of DNA-adduct from the liver constitute an important mechanism for the potentiation of aflatoxin B1-induced hepatotoxicity by ethanol.     

Serotonin in mania and in the mechanism of action of mood stabilizers: a review of clinical studies

Objectives: Serotonin (5-hydroxytryptamine, 5-HT) was implicated in the pathophysiology of manic-depressive illness as early as 1958. Although extensive evidence has accumulated since then to support 5-HT's role in depression, relatively fewer studies examined its role in mania. The purpose of this paper was to review and summarize the current state of knowledge on the role of 5-HT in mania and its treatment.

Methods: We systemically reviewed clinical studies of 1) 5-HT function in mania and 2) 5-HT in the mechanism of action of mood stabilizers, including lithium and anticonvulsants.

Results: Review showed that cerebrospinal fluid, postmortem, platelet, neuroendocrine challenge, and tryptophan depletion studies provided some evidence to support the hypothesis that a 5-HT deficit is involved in mania and that enhancement of 5-HT neurotransmission exerts a mood-stabilizing effect.

Conclusions: There is some evidence from clinical studies for the contribution of 5-HT in mania and in the mechanism of action of mood stabilizers. However, it is very likely that other neurotransmitters also play important roles. Future directions for research include 1) in vivo study of 5-HT receptor subtypes using positron emission tomography, 2) investigation of the interaction between 5-HT and other neurotransmitter systems, and 3) determination of the relationships between diagnostic subtypes of mania and 5-HT function and other neurotransmitter systems.     

PET study of the effects of valproate on dopamine D(2) receptors in neuroleptic- and mood-stabilizer-naive patients with nonpsychotic mania

OBJECTIVE: A previous study reported a higher than normal density of dopamine D(2) receptors in psychotic mania but not in nonpsychotic mania. The purpose of this study was to further examine D(2) receptor density in a larger sample of nonpsychotic manic patients by using positron emission tomography (PET) and [(11)C]raclopride. METHOD: Thirteen neuroleptic- and mood- stabilizer-naive patients with DSM-IV mania without psychotic features and 14 healthy comparison subjects underwent [(11)C]raclopride PET scans. Of the 13 patients, 10 were treated with divalproex sodium monotherapy. PET scans were repeated 2-6 weeks after commencement of divalproex sodium. D(2) receptor binding potential was calculated by using a ratio method with the cerebellum as the reference region. RESULTS: The [(11)C]raclopride D(2) binding potential was not significantly different in manic patients than in the comparison subjects in the striatum. Treatment with divalproex sodium had no significant effect on the [(11)C]raclopride D(2) binding potential in manic patients. There was no correlation between the D(2) binding potential and manic symptoms before or after treatment. CONCLUSIONS: These results suggest that D(2) receptor density is not altered in nonpsychotic mania and that divalproex sodium treatment does not affect D(2) receptor availability.     

Combination treatment of clozapine and topiramate in resistant rapid-cycling bipolar disorder

Several open-label studies or case reports have suggested the effectiveness of clozapine or topiramate in the treatment of resistant rapid-cycling bipolar patients, but none of these publications report the long-term effectiveness of these two agents in combination. The authors present a 38-year-old woman with a 22-year history of rapid-cycling bipolar I disorder who failed to respond satisfactorily to various somatic therapies, including combination therapy for complex regimens and a course of bilateral electroconvulsive therapy, but finally responded well to a combination treatment of clozapine and topiramate. Such a combination therapy led the patient to a complete remission for more than 3 years without inducing side effects such as weight gain, hyperglycemia, type II diabetes mellitus, or hyperlipidemia. In addition, she had a weight loss of 12 kg over the past 3 years. This case suggests that the combination treatment of clozapine and topiramate can be safe and effective in some resistant rapid-cycling bipolar patients.     

Evaluation of an assertiveness training program on nursing and medical students' assertiveness, self-esteem, and interpersonal communication satisfaction

This study's objective was to evaluate the effect of an assertiveness training program on nursing and medical students' assertiveness, self-esteem, and interpersonal communication satisfaction. Using a longitudinal research design, 69 participants whose scores on the Assertive Scale were < or = 50% (i.e., low assertiveness) and who were willing to participate were included and assigned to an experimental group (33 subjects) or comparison group (36 participants; participants were matched with the experimental group by grade and sex). Participants in the experimental group received eight 2-h sessions of assertiveness training once a week. Data were collected before and after training and again one month after the end of the training using the Rotter's Internal versus External Control of Reinforcement Scale, Sex Role Inventory, Assertive Scale, Esteem Scale, and Interpersonal Communication Satisfaction Inventory. The generalized estimated equation (GEE) method was used for statistical analysis. The assertiveness and self-esteem of the experimental group were significantly improved in nursing and medical students after assertiveness training, although interpersonal communication satisfaction of the experimental group was not significantly improved after the training program.