Relationship between the level of waist circumference and the impaired fasting glucose of pre-diabetes / 中华流行病学杂志

<p><b>OBJECTIVE</b>To explore the relationship between the level of waist circumference (WC) and the impaired fasting glucose (IFG) in people working for the Kailuan Enterprise.</p><p><b>METHODS</b>A total of 101 510 subjects from the employees of Kailuan Group who took part in the health examination between 2006 to 2007, with fasting plasma glucose (FPG) < 6.1 mmol/L, no history of diabetes, completed data on FPG and WC examination and without using hypoglycemic agents, were selected as the observation cohort. Subjects who did not participate in the health examination from 2010 to 2011 and had incomplete data were finally excluded, ended up with 52 099 subjects available for final analysis. According to the baseline WC measurements and its quartile in the health examinations during 2006 to 2007, people under observation were divided into four groups (first, second, third and the forth quartile groups). Multiple logistic regression analysis was used to test the relation between the increasing of WC and IFG.</p><p><b>RESULTS</b>(1) The incidence rate of IFG in the obese group was higher than that in non-obese group (10.5% vs. 6.8% , P < 0.01), along with an increasing WC noticed in the 4 quartile groups and the incidence rates of IFG were progressively increased, being 6.0%, 7.1%, 8.6% and 11.0% respectively in the total population(7.0%, 7.9%, 9.1% and 11.4% in males, 2.5%, 4.6%, 6.8% and 9.8% in females). (2)Results from the multiple logistic regression analysis showed that, when compared with the first quartile group, the second, third and fourth quartile groups had increased risks of IFG after adjustment on age, gender and other risk factors in the total population, with the OR values being 1.03, 1.15 and 1.30 respectively. After adjusting the above factors in genders, we also noticed the increased risks of IFG, with the OR value being 1.45, 1.66 and 2.08 in males, while 1.00, 1.09 and 1.23 in females, respectively. The influence of the second and third quartile groups on IFG was not significant in females, however.</p><p><b>CONCLUSION</b>The incidence of IFG showed an increasing trend with the increase of WC.</p>

Metabolism of mitomycin C by human liver microsomes in vitro / 药学学报

To provide the profiles of metabolism of mitomycin C (MMC) by human liver microsomes in vitro, MMC was incubated with human liver microsomes, then the supernatant component was isolated and detected by HPLC. Types of metabolic enzymes were estimated by the effect of NADPH or dicumarol (DIC) on metabolism of MMC. Standard, reaction, background control (microsomes was inactivated), negative control (no NADPH), and inhibitor group (adding DIC) were assigned, the results were analyzed by Graphpad Prism 4. 0 software. Reaction group compared with background control and negative control groups, 3 NADPH-dependent absorption peaks were additionally isolated by HPLC after MMC were incubated with human liver microsomes. Their retention times were 10. 0, 14. 0, 14. 8 min ( named as Ml, M2, M3) , respectively. Their formation was kept as Sigmoidal dose-response and their Km were 0. 52 (95% CI, 0. 40 - 0.67) mmol x L(-1), 0. 81 (95% CI, 0. 59 - 1. 10) mmol x L(-1), 0. 54 (95% CI, 0. 41 -0. 71) mmol x L(-1) , respectively. The data indicated that the three absorption peaks isolated by HPLC were metabolites of MMC. DIC can inhibit formation of M2, it' s dose-effect fitted to Sigmoidal curve and it' s IC50 was 59. 68 (95% CI, 40. 66 - 87. 61) micromol x L(-1) , which indicated DT-diaphorase could take part in the formation of M2. MMC can be metabolized by human liver microsomes in vitro, and at least three metabolites of MMC could be isolated by HPLC in the experiment, further study showed DT-diaphorase participated in the formation of M2.

Effect of constitutive androstane receptor on the cytotoxicity of mitomycin C and 5-(aziridin-1-yl)-3-hydroxymethyl-1-methylindole-4,7-dione / 药学学报

This study is to evaluate the cytotoxicity of mitomycin C (MMC) and its analogue 5-(aziridin-1-yl)-3-hydroxymethyl-1-methylindole-4,7-dione (629) as well as the effect of transfection of constitutive androstane receptor (CAR) on their biological effects. HepG2 cells were transfected with the plasmids mCAR1/pCR3 mediated by liposome. Vector pCR3 was used as control. Transfected cells were screened by G418 resistance and limiting dilution. The expressions of plasmid mCAR1/pCR3 and CYP2B6 mRNA were detected by RT-PCR; Cytotoxicities of MMC and 629 in vitro were evaluated in g2car cells and HepG2 cells by MTT method under anaerobic and aerobic conditions. mRNA expression of CAR and CYP2B6 can not be detected in HepG2 cells and HepG2/pCR3 cells but can in g2car cells. It is shown that plasmid mCAR1/pCR3 was transfected into g2car cells successfully and target CYP2B6 was transactivated by CAR. To compare with aerobic and anaerobic, the cytotoxicities of MMC and 629 to HepG2 cells and g2car cells had significantly enhanced (P < 0.05), and transfect CAR gene can improve the cytotoxicity of MMC (P < 0.05), but not 629 (P > 0.05). Furthermore, CYP2B6 is one master enzyme for the metabolism of MMC and not 629. Transfection of CAR can increase expression of CYP2B6 mRNA in HepG2 cells, and can affect cytotoxicities of MMC and 629.

Effect of in vitro and in vivo treatment with mitomycin C on activities of CYP2D1/2, CYP2C11, and CYP1A2 in rat liver / 药学学报

<p><b>AIM</b>To evaluate the effect of in vitro and in vivo treatment with mitomycin C (MMC) on activities of CYP2D1/2, CYP2C1 , and CYP1A2 in the liver of male rats.</p><p><b>METHODS</b>Using HPLC to determine the activities of the three isoenzymes in rat liver microsomes by detecting the specific metabolites of their substrates after treatment with inducers in vivo or inhibitors in vitro.</p><p><b>RESULTS</b>In vitro, MMC inhibited the activity of CYP2D1/2, CYP2C11, and CYP1A2 in dexamethasone-induced microsomes by (19 +/- 6)% (P < 0.05), (85 +/- 10)% (P < 0.01), and (36 +/- 6)% (P < 0.05), respectively, and decreased the activity of CYP1A2 in beta-naphthoflavone-induced microsomes by (58 +/- 6)% (P < 0.01). Rats were injected intraperitoneally with 20% of the LD50 of MMC for 3 or 6 d. The treatment showed no significant effect on microsomal activities of CYP2D1/2, CYP2C11 or CYP1A2.</p><p><b>CONCLUSION</b>MMC can inhibit the activities of CYP2D1/2, CYP2C11, and CYP1A2 in rat liver microsomes in vitro, but it showed no significant effect on the activities of the three isoenzymes in vivo.</p>