Effects of Shakuyaku-Kanzo-to on Extrapyramidal Symptoms During Antipsychotic Treatment: A Randomized, Open-Label Study.

Extrapyramidal symptoms (EPS) are common adverse effects of antipsychotic treatment. This study examined the effects of the traditional Japanese herbal medicine (kampo) shakuyaku-kanzo-to on EPS during antipsychotic treatment. Twenty-two Japanese patients with psychiatric disorders who had developed EPS during antipsychotic treatment were randomly allocated to receive either shakuyaku-kanzo-to (7.5 g/d) or biperiden (3 mg/d) for 2 weeks. Extrapyramidal symptoms were evaluated using the Drug-Induced Extrapyramidal Symptom Scale (DIEPSS) and the Barnes Akathisia Rating Scale. Plasma levels of the monoamine metabolite homovanillic acid and serum prolactin levels were measured to investigate the mechanisms of action of shakuyaku-kanzo-to. Twenty of the 22 patients completed the study (10 patients in the shakuyaku-kanzo-to group and 10 patients in the biperiden group). There was a time effect on the Drug-Induced Extrapyramidal Symptom Scale total score (P < 0.01), suggesting that both shakuyaku-kanzo-to and biperiden decreased EPS. Notably, there was a time × drug interaction in dystonia, suggesting that shakuyaku-kanzo-to had a greater effect on dystonia compared with biperiden. No significant changes were observed in plasma homovanillic acid or serum prolactin levels after 2 weeks of treatment in either group. The effects of shakuyaku-kanzo-to on abnormal muscle tonus and dopamine D2 receptors may have contributed to improve EPS. These results suggest that shakuyaku-kanzo-to may be useful in decreasing EPS, especially dystonia, in patients undergoing treatment with antipsychotic agents.

Impacts of age on plasma monoamine metabolite concentrations in a large cohort of healthy individuals.

The measurement of plasma concentrations of monoamine metabolites is a useful method for inferring the dynamics of monoamine metabolites in the brain. To clarify effects of age and sex on plasma monoamine metabolites levels, we used high-performance liquid chromatography to measure plasma levels of homovanillic acid (HVA), free and total 3-methoxy-4-hydroxyphenylglycol (MHPG), and 5-hydroxyindoleacetic acid (5-HIAA) in healthy men and women of various ages (n=214). In all plasma monoamine metabolites, there were significant differences across the age groups, and multiple comparisons revealed that older subjects had higher levels than younger subjects. Moreover, significant positive correlations were found between age and plasma levels of HVA, free MHPG, total MHPG, and 5-HIAA. On the other hand, plasma concentrations of monoamine metabolites were not influenced by sex, except for total MHPG for which the plasma levels were significantly higher in men than in women. Age-related changes in monoamine oxidase and renal function might affect our results. This large cohort survey provides further evidence to be cautiously aware of age effects when regarding plasma monoamine metabolites levels as reflections of central activity.

[Takotsubo-like left ventricular dysfunction with delayed recovery of left ventricular shape: a case report].

A 70-year-old woman was admitted to our hospital because of left ventricular dysfunction, which was observed after permanent pacemaker implantation in another hospital. The left ventricular dysfunction was apical ballooning. Left ventriculography demonstrated takotsubo-like shape. However, the dysfunction did not improve immediately with medical treatment. In this case, 75% stenosis was observed in the left anterior descending artery. We suppose that this lesion corresponded to the delayed recovery of the dysfunction and performed coronary intervention. The takotsubo-like shape improved gradually for about 1 year. Whether the coronary intervention was effective for the recovery of the dysfunction is unclear, this clinical course was interesting in evaluating the delayed recovery of takotsubo-like left ventricular dysfunction.

A two-generation reproductive toxicity study of n-butylbenzene in rats.

N-butylbenzene (n-BB), which is suspected of having endocrine disrupting effects, was administered orally by gavage at dose levels of 0, 30, 100, and 300 mg/kg/day to groups of Crj: CD (SD) IGS rats (24 males and 24 females per group) over 2 generations, and the effects on fertility of the parental animals and development/growth of the offspring were investigated. In the F0 and F1 parental animals, n-BB at the doses of 30 mg/kg/day and above increased the liver weights, and the doses of 100 and 300 mg/kg/day increased the kidney weights and caused histopathological changes in the liver and kidney. Moreover, the dose of 300 mg/kg/day also increase adrenal gland weights and there was a tendency for inhibition of body weight gain. With respect to effects on fertility, no significant findings were noted in the F0 parental males and females. Furthermore, it was concluded that n-BB did not induce serious reproductive toxicity in the F1 parental animals and no effects on the endocrine system were recognized. In the F1 and F2 offspring, n-BB at 300 mg/kg/day increased the thymus weights.