Effects of 17ß-estradiol and progesterone on the production of adipokines in differentiating 3T3-L1 adipocytes: Role of Rho-kinase.

Effect of female sex hormones on the production/release of adipocyte-derived cytokines has been debatable. Furthermore, whether the cellular signaling triggered by these hormones involve Rho-kinase has not been investigated yet. Therefore, in this study, effects of 17ß-estradiol and progesterone as well as the Rho-kinase inhibitor, Y-27632 on the level of adipokines such as resistin, adiponectin, leptin, TNF-α and IL-6 were investigated in 3T3-L1-derived adipocytes. Differentiation was induced in the post-confluent preadipocytes by the standard differentiation medium (Dulbecco's modified Eagle's medium with 10% fetal bovine serum together with the mixture of isobutylmethylxanthine, dexamethasone and insulin) in the presence of 17ß-estradiol (10(-8)-10(-7)M), progesterone (10(-6)-10(-5)M), the Rho-kinase inhibitor, Y-27632 (10(-5)M) and their combination for 8days. Measurements of the adipokines were performed in the culturing medium by ELISA kits using specific monoclonal antibodies. 17ß-estradiol elevated resistin but decreased adiponectin and IL-6 levels; however, it did not alter the concentration of leptin and TNF-α. Y-27632 pretreatment inhibited the rise of resistin and the fall of adiponectin by 17ß-estradiol without any effects by its own. Progesterone did not change resistin, leptin and TNF-α level; however, it elevated adiponectin and decreased IL-6 production. Neither 17ß-estradiol nor Y-27632 was able to antagonize the increase of adiponectin and the reduction of IL-6 levels by progesterone. While Y-27632 alone lowered IL-6 level, it increased leptin and TNF-α concentration without altering resistin and adiponectin. In conclusion, 17ß-estradiol could modify adipokine production in 3T3-L1 adipocytes with the actions some of which involve Rho-kinase mediation.

Proton pump inhibitors omeprazole, lansoprazole and pantoprazole induce relaxation in the rat lower oesophageal sphincter.

OBJECTIVES: We aimed to investigate effects of the proton pump inhibitors (PPIs) omeprazole, lansoprazole and pantoprazole, which are currently used for the treatment of hyperacidity and gastro-oesophageal reflux, on the reactivity of the isolated rat lower oesophageal sphincter. METHODS: Omeprazole, lansoprazole and pantoprazole (all 10(-9) -10(-3) m, cumulatively) were tested on carbachol-induced (10(-6) m) contraction. In addition, the effects of PPI preincubation (all 10(-3) m) on the contractions induced by cumulative carbachol (10(-9) -10(-5) m), angiotensin-2 (10(-9) -10(-5) m) or electrical field stimulation (EFS; 40 V, 32 Hz, 1 ms, 10 s) were assessed. Finally, the effects of PPI on the spontaneous contractile activity of the tissue were also evaluated. KEY FINDINGS: PPI relaxed precontracted lower oesophageal sphincter in a concentration-dependent manner and suppressed carbachol-, angiotensin- and EFS-induced contractions. Furthermore, PPI attenuated spontaneous contractile activity of the tissue. CONCLUSIONS: Omeprazole, lansoprazole and pantoprazole had a suppressor effect on lower oesophageal sphincter contractions.

Association of angiotensin converting enzyme gene insertion/deletion polymorphism with lung cancer in Turkey.

Angiotensin-converting enzyme (ACE) plays an important role in the physiological control of blood pressure and inflammation. We investigated an insertion/deletion (I/D) polymorphism of the gene for ACE in relation to cardiovascular, cerebrovascular, neurodegenerative, and inflammatory diseases. The purpose of the present study was to investigate a possible association between lung cancer and insertion/deletion polymorphism of the ACE gene. A total of 125 patients with lung cancer and 165 control subjects were enrolled in the present study. ACE I/D genotypes were determined by polymerase chain reaction. Allelic frequencies and genotype distribution of the ACE I/D polymorphism in the patient group were significantly different from control subjects (ACE II genotype 29.6 vs. 17.6%, P = 0.011; ACE I allele 49.6 vs. 39.4%, P =0.009). Our data suggest that the ACE I/D polymorphism could be a risk factor for patients with lung cancer.