Cortisol levels during an oral glucose tolerance test in lean and obese women

Because of the similarities between Cushing's syndrome and insulin resistance syndrome,cortisol metabolism in obesity has been investigated in numerous studies. Our study investigates serum glucose, insulin, and cortisol response to oral glucose stimulation in a group of obese and lean normotensive, normolipidemic, and glucose-tolerant premenopausal women. Twenty-one obese [body mass index (BMI) 37Z +/- 6.3 kg/m2) and 14 lean (BMI: 21.5 +/- 1.0 kg/m2) age-matched healthy premenopausal women were included in the study. Serum glucose, insulin, and cortisol levels were measured at 30-minute intervals during 120 minutes of oral glucose tolerance testing (OGTT). Mean serum glucose and insulin levels were significantly higher in the obese group compared with lean subjects, and cortisol levels were similar during OGTT. There was not a significant difference for cortisol area under the curve (AUC) during OGTT between the two groups. No correlation between cortisol AUC, insulin AUC, and glucose AUC was noted for both groups. During OGTT, a decrease in cortisol levels was observed in both groups. The decrement occurred at 30 minutes of the OGTT in the obese group and at 60 minutes of the OGTT in the lean group. At 90 and 120 minutes of the OGTT, serum cortisol levels were similar to basal levels in both the obese group and the lean group. Previous studies reported altered hypotalamic-pituitary-adrenal axis activity, altered levels of urinary cortisol excretion, and increased metabolic clearance of cortisol in obesity. In our study in obese women, the only detected difference from lean subjects was a quicker suppression and recovery in serum cortisol levels after glucose administration.     

Progestin-inflammatory cytokine interactions affect matrix metalloproteinase-1 and -3 expression in term decidual cells: implications for treatment of chorioamnionitis-induced preterm delivery

CONTEXT: Chorioamnionitis (CAM)-elicited preterm delivery (PTD) is associated with elevated amniotic fluid levels of IL-1beta and TNF-alpha. We hypothesized that IL-1beta and TNF-alpha may induce matrix metalloproteinase (MMP)-1 and MMP-3 activity to promote PTD by degrading decidual and fetal membranes and cervical extracellular matrix. OBJECTIVE: Our objective was to evaluate: 1) MMP-1 and MMP-3 expression in decidual sections from uncomplicated term, idiopathic preterm, and CAM-complicated deliveries, and 2) the separate and interactive effects of IL-1beta, TNF-alpha, medroxyprogesterone acetate (MPA), and a p38 MAPK inhibitor (SB203580) on MMP-1 and MMP-3 expression in term decidual cells (DCs). INTERVENTIONS AND MAIN OUTCOME MEASURES: Decidua were immunostained for MMP-1 and MMP-3. Cultured term DCs were incubated with estradiol (E2) or E2 plus MPA with or without IL-1beta or TNF-alpha with or without SB203580. ELISA and Western blotting assessed secreted MMP-1 and MMP-3 levels, quantitative real-time RT-PCR assessed mRNA levels, and substrate gel zymography was used to determined MMP-1 and MMP-3 proteolytic activity. RESULTS: MMP-1 and MMP-3 immunostaining was more prominent in CAM-complicated decidua vs. control preterm and term decidual specimens (P < 0.05). Compared with basal outputs by DCs incubated with E2, TNF-alpha enhanced MMP-1 and MMP-3 secretion by 14 +/- 3- and 9 +/- 2-fold, respectively, and IL-1beta increased MMP-1 and MMP-3 secretion by 13 +/- 3- and 19 +/- 2-fold, respectively (P < 0.05). Addition of MPA lowered basal MMP-1 and MMP-3 outputs by 70%, whereas the TNF-alpha- and IL-1beta-enhanced MMP-1 and MMP-3 levels were blunted by more than 50% (P < 0.05). SB203580 suppressed TNF-alpha- and IL-1beta-induced MMP-1 and MMP-3 secretion by severalfold. Western blotting confirmed the ELISA results, and mRNA levels corresponded with MMP-1 and MMP-3 protein levels. MMP-1 and MMP-3 proteolytic activity was confirmed by substrate gel zymography. CONCLUSION: Augmented DC-expressed MMP-1 and MMP-3 in CAM-complicated pregnancies may promote PTD via decidual, fetal membrane, and cervical extracellular matrix degradation. Effects of progestin-p38 MAPK signaling inhibition on cytokine-enhanced MMP-1 and MMP-3 expression in term DCs suggest alternative mechanisms to prevent CAM-induced PTD.     

Role of Capsaicin-Sensitive Nerves in Gastric and Hepatic Injury Induced by Cold-Restraint Stress

The role of capsaicin-sensitive afferent fibers on cold-restraint stress-induced gastric and hepatic injury was examined at the macroscopic and ultrastructural levels. Wistar albino rats were treated with capsaicin either locally (intragastric, perivagal, and periceliac) or systemically (neonatal, intraperitoneal). Perineural and neonatal treatment with capsaicin was used to denervate afferent fibers, while intragastric capsaicin treatment would have activated mucosal afferent fibers just before the stress exposure. Capsaicin decreased significantly the formation of macroscopic gastric lesions caused by stress in all treatment groups. At the electron microscopic level, however, denervation of vagal afferent fibers with capsaicin was most effective in prevention of cellular injury in gastric mucosa. In the liver, systemic denervation of afferent fibers completely inhibited stress-induced cellular damage, while denervation of afferent fibers in vagus and splanchnic nerve was partially effective. Central neural pathways sensitive to capsaicin may mediate formation of both gastric and hepatic injury resulting from stress.     

Left ventricular thrombosis is associated with increased mean platelet volume in patients with dilated cardiomyopathy and sinus rhythm

OBJECTIVE: Dilated cardiomyopathy has been associated with left ventricular thrombosis, which leads to substantial morbidity and mortality as a site for peripheral emboli. There are some studies on patients with dilated cardiomyopathy showing altered haemostasis and platelet behaviour despite sinus rhythm. Mean platelet volume, which is the most accurate and simple estimate of platelet reactivity, may be associated with the development of left ventricular thrombosis. METHODS AND RESULTS: We prospectively enrolled 48 consecutive patients with dilated cardiomyopathy and sinus rhythm with left ventricular thrombosis and compared them with an age-sex-matched control group having dilated cardiomyopathy without left ventricular thrombosis. We found that in patients with left ventricular thrombosis mean platelet volume is significantly higher than those without (9.5 +/- 0.8 vs. 8.7 +/- 0.6, p < 0.001). CONCLUSIONS: Mean platelet volume is increased in patients with dilated cardiomyopathy and sinus rhythm having left ventricular thrombosis. This might be reflecting a causal relationship, which in turn requires further study to establish the role of antiplatelet agents both in prevention and in treatment.     

Lipid profile of patients with aortic stenosis might be predictive of rate of progression

Background

Aortic stenosis is one of the most commonly encountered valvular pathology requiring surgery in developed countries. There are similarities between risk factors for coronary atherosclerosis and the development of aortic stenosis. We designed a retrospective study, evaluated the lipid profile and previous echocardiographic recordings of patients with aortic stenosis, and searched the association of rate of progression and lipid profile.

Methods and results

The annual rates of progression in the peak and mean aortic gradients were 8.5 ± 3.2 and 6.7 ± 2.2 mm Hg/year, respectively. We classified the annual rate of progression of peak aortic gradient into 2 groups, group 1 with <10 mm Hg (“slow progressors”) and group 2 with ≥10 mm Hg annual rate of progression (“fast progressors”). The annual rate of progression in group 1 was significantly higher than that in group 2, both in peak and mean aortic gradients (12 ± 2 mm Hg and 6.4 ± 1.6 mm Hg; 9 ± 1.3 mm Hg and 5.2 ± 1.1 mmHg; P <.001 for both). There was a highly significant difference between group 1 and group 2 for total cholesterol/high-density lipoprotein (HDL) cholesterol level ratio (7.1 ± 1.4 vs 5.2 ± 1.3, P <.001). There was a significant correlation between annual rate of progression in peak gradient and total cholesterol/HDL cholesterol level ratio (r = 0.399, P = .009). Smoking (P = .024, Beta = 0.26), presence of coronary heart disease (P = .011, Beta = 0.31), and total cholesterol/HDL cholesterol level ratio (P = .004, Beta = 1.98) were independently predictive of fast progression of the peak aortic gradient in the regression analysis.

Conclusion

In a small group of patients from Turkey with aortic stenosis, there seems to be an association between the rate of progression and total cholesterol/HDL cholesterol level ratio, with fast progression occurring in the group with higher ratios.     

Estrogenicity of isoflavones on human endometrial stromal and glandular cells

Endometrium consists of different cell populations such as epithelial and stromal cells and is mainly regulated by sex steroids. Isoflavones are plant-derived estrogenic compounds that have estrogenic and antiestrogenic properties in a cell-specific manner. We hypothesized that one of the potential health benefits of isoflavones may be their ability to regulate endometrial cell function. The present study was conducted to assess estrogenic and/or antiestrogenic effects of isoflavones (genistein, genistin, daidzein, and daidzin) in cultured human endometrial stromal and glandular (Ishikawa) cells by MTT colorimetric cell proliferation assay, proliferating cell nuclear antigen expression, and alkaline phosphatase activity assays. Experiments were performed in a time- (24-96 h) and concentration-dependent (10(-12) to 10(-5) M) manner. All isoflavones used in the present study induced endometrial stromal and Ishikawa cell proliferation when compared with control (vehicle) group in a time- (at 48 h and afterward) and concentration-dependent manner (at 10(-8) M and above) (P < 0.05). However, isoflavones (at 10(-8) and above concentrations) were also antiestrogenic when combined with estradiol (E(2)) (P < 0.05). The isoflavones revealed a weak estrogenic activity (39-67% less than E(2)) as assessed by alkaline phosphatase activity (P < 0.05), but when administered together with E(2), they antagonized estrogen induced alkaline phosphatase activity by 36-89% (P < 0.05). We conclude that, although isoflavones alone have weak estrogenic effects on endometrial stromal and glandular cells, in the presence of E(2) they act as antiestrogens.