Daily intake of polyamine-rich Saccharomyces cerevisiae S631 prevents osteoclastic activation and bone loss in ovariectomized mice.

An imbalance in the sophisticated regulation between bone-resorbing osteoclasts and bone-forming osteoblasts leads to the pathogenesis and etiology of certain metabolic bone diseases including osteoporosis. Certain polyamines are related to the pathophysiology of some disorders, including Alzheimer's disease, infectious disease, cancer, and aging. Recently, we demonstrated that oral intake of polyamines (spermidine and spermine) prevented bone loss through preferential disturbance of osteoclastic activation in ovariectomy-induced mouse model of postmenopausal osteoporosis. Here, we showed that daily oral supplementation of a diet containing polyamine-rich Saccharomyces cerevisiae S631 significantly inhibited osteoclastic activation as well as reduction of bone volume in the cancellous bone without affecting uterine weight in ovariectomized mice. Our findings recommend that daily oral supplementation with polyamine-rich yeast diet would be beneficial for prophylaxis of metabolic bone diseases associated with abnormal osteoclast activation.

Comparison of cytochrome p450 mediated metabolism of three central nervous system acting drugs.

The investigation of cytochrome P450 (CYP) mediated metabolism reactions by determination of enzyme kinetic parameters, Michaelis constant (K(m)), maximum reaction velocity (V(max)), and intrinsic clearance (CL(int)) is important aspects in discovery and development of drugs. The kinetic parameters can be used to predict the clearance prior to human administration and for better understanding the mechanism of clearance in vivo. In this study, the metabolic activities of three major hepatic CYP isoforms (2C19, 2D6, and 3A4) were investigated on structurally different central nervous system (CNS) acting drugs, amitriptyline, fluphenazine, and dothiepin. By using our novel in vitro evaluation system, we could compare the kinetic parameters for the metabolism of fluphenazine and dothiepin for the first time. Comparing CL(int) values thus obtained, we concluded that 2C19 could be predominant for metabolic activity on tricyclic antidepressants as expected, but not on phenothiazine-related antipsychotic drugs. Since the metabolism of CNS drugs is susceptible to single nucleotide polymorphisms of human gene, our results suggest that phenothiazine could be an alternative to clinical application of CNS drugs.