Prospective study of warfarin dosage requirements based on CYP2C9 and VKORC1 genotypes.

Polymorphisms in CYP2C9 and VKORC1 have been shown to be associated with warfarin dose requirements and could be used to predict warfarin dose. We conducted a prospective study in which warfarin dose was prescribed based on CYP2C9 and VKORC1 polymorphisms in 108 Han-Chinese patients without prior warfarin treatments. Using the genotype-based dosing, 83% of patients reached stable, therapeutic international normalized ratio (INR) within 2 weeks of treatment initiation and none of the patients developed clinical bleeding or thromboembolic event. Ten percent (11) of patients with INR > 4 and no clinical bleeding were detected during this study. At 12 weeks, 69% of the patients' maintenance doses matched the prediction. Dosing algorithms incorporating genetic factors, age, and body surface area were developed, which could explain up to 62% of the total variation (R(2) of 0.62). This study demonstrated that pharmacogenetics-based dosing could improve time to stable, therapeutic INR, reduce adverse events, and achieve high sensitivity.

A novel ortho-dehalogenation reaction of 2-chlorocinnamic acid catalyzed by the pink yeast Rhodotorula rubra Y-1529.

In the present study, a resting cells suspension of Rhodotorula rubra Y-1529 was shown to have the capacity to perform an ortho-dehalogenation reaction on 2-chlorocinnamic acid. The results from the biodegradation of U-[14C]benzoic acid, cinnamic acid, 3-chlorocinnamic acid and 4-chlorocinnamic acid suggest that the first step of the ortho-dehalogenation reaction occurred during the oxidation of the unsaturated C3 side chain of 2-chlorocinnamic acid to 2-chlorobenzoic acid. None of the 2-chlorobenzoic acid was found in the biodegradation system, suggesting that this step was a highly regulated step. After the side-chain oxidation reaction, the hydroxylation of the benzene ring was determined to be at the para-position first, followed by the meta-position. The occurrence of 3:4-position ring fission reactions and the production of the final product, CO2, was proven by the biodegradation of U-[14C] benzoic acid. This oxidative dehalogenation reaction catalyzed by R. rubra was found to be regiospecific for 2-chlorocinnamic acid; the chloride ion was probably removed after the ring fission reaction. A pathway of the ortho-dehalogenation reaction of 2-chlorocinnamic acid catalyzed by R. rubra was proposed based on these data.

[Good regulation of acupuncture in simple obesity patients with stomach-intestine excessive heat type].

In order to investigate the regulatory effect of acupuncture on obesity patients with the Stomach-Intestine Excessive Heat Type, the pre-acupunctural and post-acupunctural obesity index and biochemical indices of 718 patients with simple obesity was observed. It was showed that the marked weight loss effects was achieved in the cases by acupuncture, while the biochemical indices improved. It suggests that acupuncture had a good regulatory effect on the function of nerve, endocrine, digestion and energy metabolism.

[Effect of acupuncture and moxibustion on antiobesity in the variation of plasma cyclic nucleotide and the function of vegetative nervous system].

The authors observed the changes of the obesity index, lipid index, the equilibrium indices of the vegetative nervous system (Y value) and the plasma cAMP of 46 cases of simple obese before and after acupuncture. Of 46 cases, 39 were of the non-sthenia of liver-Yang (group 1) and 7 of the sthenia of liver-Yang (group 2). It was found that the sympathetic nervous function of the patients in group 1 was markedly higher than the normal. In both of them, the lipid metabolism was abnormal and the content of cAMP in plasma was significantly lower than the normal. The marked effects were achieved on the cases which received one course of treatment (1 month) by acupuncture, the total effective rate being 84.8%. The acupuncture brought about not only antiobesity effect but biphase changes on the blood pressures and Y value as well, that is, acupuncture raised the blood pressures and Y value of the patients in group 1 but reduced the blood pressures and Y value of the patients in group 2. In addition, acupuncture brought about good regulation effect on lipid metabolism and plasma cAMP of patients. This suggests that the regulation effect of acupuncture on plasma cAMP of patients with simple obese might be an important link by which antiobesity effect may be achieved.