[Effects of bofu-tsusho-san, a traditional Chinese medicine, on body fat accumulation in fructose-loaded rats].

The effects of Bofu-tsusho-san (BOF), a traditional Chinese medicine, on fructose-induced hypertriglyceridemia and body fat accumulation were investigated in female SD rats. Rats were allowed to drink ad libitum 25% (w/w) fructose solution for 6 weeks. BOF was administered to the rats as an experimental diet containing 1.5% or 4.5% (w/w) of BOF during the fructose-loading period. BOF suppressed body weight gain and prevented the elevation of serum triglyceride levels and body fat accumulation in fructose-loaded rats without affecting food and fructose intake. Furthermore, BOF prevented the increase of triglyceride content in the liver and the reduction of mitochondrial cytochome c oxidase activity in the brown adipose tissue induced by fructose. From these results, it has been suggested that BOF has a preventive effect against the body fat accumulation caused by excess intake of sugar or other fructose-containing foods. The inhibition of triglyceride synthesis in the liver, and the enhancement of lipolysis in adipocytes and of thermogenesis in brown adipose tissue have been presumed as the mechanisms of action of BOF.

Elucidation of the mode of interaction of thermolysin with a proteinaceous metalloproteinase inhibitor, SMPI, based on a model complex structure and a structural dynamics analysis.

SMPI is a proteinaceous microbial metalloproteinase inhibitor that was isolated from Streptomyces nigrescens TK-23 in 1979. SMPI is known to selectively inhibit the metalloproteinases in the gluzincin family, according to the Rawling and Barrett classification. There has been no report on the interaction of a metalloproteinase in the family of gluzincins with its specific proteinaceous inhibitor. We have solved the solution structure of SMPI by NMR. Here, we report the binding mode of SMPI to thermolysin, based on the model complex structure generated using our high-resolution NMR structure of SMPI and the crystal structure of thermolysin. The obtained complex model shows that the extruded loop of SMPI, with the scissile bond Cys64-Val65, is complementary in shape to the active cleft of thermolysin. In the complex, the Cys64 (P1) carbonyl oxygen atom can form a tetrahedral coordination to the active zinc in thermolysin, and simultaneously, the methyl groups of Val65 (P1') are closely located in the hydrophobic S1' pocket in thermolysin. From the electrostatic potential surface calculation, the active loop of SMPI and the active cleft in thermolysin have been shown to be complementary in the surface charge distribution, resulting in the stabilization of the complex. The apparently large active loop is less flexible, but maintains a conformation in the nano- to picosecond time-scale, as elucidated from the 15N spin relaxation analysis. This is a quite different structural feature of SMPI from the flexible binding loop generally found in the serine proteinase inhibitors, such as SSI and eglin c, and can be related to the narrow specificity of SMPI. The present study provides the first insight into the interaction between a proteinaceous inhibitor and a gluzincin metalloproteinase.

In vitro and in vivo antibacterial activities of CS-940, a new fluoroquinolone, against isolates from patients with respiratory infections.

We compared the in vivo and in vitro activities of CS-940, a new fluoroquinolone, with those of a group of other drugs. The activities of CS-940 against gram-positive cocci and gram-negative rods, including methicillin-susceptible Staphylococcus aureus and penicillin-resistant Streptococcus pneumoniae, were comparable to those of tosufloxacin, with MICs at which 90% of the strains were inhibited (MIC90s) of 0.5 microg/ml or less. Against methicillin-resistant S. aureus, CS-940 was as active as tosufloxacin, with a MIC90 of 16 microg/ml. The efficacy of CS-940 against murine respiratory infections due to S. pneumoniae or Haemophilus influenzae was better than those of tosufloxacin and sparfloxacin. The efficacy of oral doses of CS-940 reflected not only potent in vitro activity but also a high transmigration ratio from the bloodstream to lung tissues.

Accelerative effect of shikonin, alkannin and acetylshikonin on the proliferation of granulation tissue in rats.

The present study was carried out to compare the accelerative effect of shikonin (R-type), alkannin (S-type), and acetylshikonin on the proliferation of granulation tissue in rats, and to elucidate the correlation between the potency of the effect and their optical activity. Koushikon mainly contained the R-type of acetylshikonin, and Nanshikon mainly contained the S-type of acetylshikonin. Each compound produced a dose-dependent acceleration of the cotton pellet-induced granuloma formation. In comparing identical doses of shikonin, alkannin and acetylshikonin, the potency of their accelerative effects on the proliferation of granulation tissue was about the same. This result suggests that their absolute configurations (R-type or S-type) and their acetylation on the hydroxy group of the sidechain of shikonin or alkannin may not be important in producing the effect.

Comparative study on the accelerative effect of "koushikon" and "nanshikon" and their constituents on proliferation of granuloma tissue in rats.

This study was carried out to compare the accelerative effect in ether extracts of "Koushikon" and "Nanshikon" on proliferation of granuloma tissue in rats, and to elucidate this effect on optical isomer of naphthoquinone derivatives in those extracts. The content of total naphthoquinone derivatives in the ether extracts of Koushikon and Nanshikon were found to be 56.1% and 25.4%. Among naphthoquinone derivatives, Koushikon contained mostly acetyl derivative and Nanshikon mostly teracryl derivative. The percentage of R-type (shikonin-type) in total naphthoquinone derivatives of the extracts was 85.5% and 3.8%. Each ether extract showed a dose-dependent acceleration on the cotton pellet-induced granuloma formation. Comparison with corresponding doses containing the same quantity of naphthoquinone derivatives showed the accelerative potency of ether extracts of Koushikon and Nanshikon to be about the same. The result suggests that the accelerative effect on proliferation of granuloma tissue depends primarily on the total content of naphthoquinone derivatives, and not on the ratio of the optically active isomers.

Comparison of converting enzyme inhibitor and calcium channel blocker in SHR with nephrotoxic serum nephritis.

In order to compare the protective effects of angiotensin converting enzyme inhibitors (ACEI) and calcium channel blockers (CCB) on the renal function in experimental nephritis, nephrotoxic serum nephritis was induced in male spontaneously hypertensive rats (SHR). The above drugs were then chronically administered to different groups, as follows: the ACEI-treated group (n = 7) received captopril (150 mg/kg/day), and the CCB-treated group (n = 6) was given both nifedipine (40 mg/kg/day) and nisoldipine (20 mg/kg/day). The control group (n = 8) received a placebo. Although the control group developed marked hypertension and proteinuria, the rats treated with either ACEI or CCB demonstrated a significant and equivalent decrease in mean arterial pressure and urinary protein excretion. At 15 weeks after the injection of nephrotoxic serum, all rats were anesthetized with Inactin, and the glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured. In the control group, GFR and RPF were markedly attenuated. However, both were preserved at much higher levels in the ACEI-treated group, and GFR was also maintained to a similar degree in the CCB-treated group. Histological studies were carried out after the clearance studies. As a result, it was found that the ACEI treatment significantly limited the development of glomerulosclerosis, whereas CCB modestly ameliorated the glomerular structural lesions. Moreover, ACEI significantly reduced the serum cholesterol, while CCB did not exert such an effect. These results suggest that both ACEI and CCB have a therapeutic effect in experimental glomerulonephritis models which are accompanied by hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

[The efficacy of combined use of 1 alpha-hydroxyvitamin D3 with calcium supplements in the treatment of osteoporosis].

Synthetic analogue of active vitamin D metabolite, 1 alpha (OH) D3, has been widely used in the treatment of osteoporosis. However, the most effective method of treatment is yet to be established. Importance of calcium supplement to improve the calcium metabolism in osteoporosis is also reported by many authors. We have studied the combined effects of 1 alpha (OH)D3 with calcium supplement in preventing progressive decrease of bone mass in patients with osteoporosis. Sixty-six cases of postmenopausal and senile osteoporosis were divided into two groups: one treated with calcium alone 1,000 mg a day and the other treated with calcium 1,000 mg and 1 alpha (OH)D3 0.5 microgram a day, and both groups were followed for 24 months. Bone mass was evaluated by microdensitometry of the roentgenograms of the second metacarpal bone. The results revealed that the combined use of 1 alpha (OH)D3 with calcium has a significantly more favorable effect than the use of calcium alone in preventing bone loss. Therefore, 1 alpha (OH)D3 with calcium is useful in the treatment of osteoporosis. The conclusion would be further confirmed with longer term study and a more accurate method of measuring bone mass.