Endocannabinoid receptor blockade increases hepatocyte growth factor and reduces insulin levels in obese women with polycystic ovary syndrome

There is evidence from animal and in-vitro studies that activation of the endocannabinoid system (EC) through cannabinoid receptor 1 (CB-1) is associated with liver injury, inflammation and hepatocellular carcinoma.1 Data suggests endogenous cannabinoids (EC) are related to fatty liver metabolism with a role in non-alcoholic fatty liver disease (NAFLD) through modulating lipid metabolism that may be ameliorated by CB1 receptor antagonism with rimonabant.2 This is of particular importance as NAFLD is the most common cause of chronic liver disease with liver dysfunction leading liver cirrhosis. The diagnosis of NAFLD can only be confirmed by a liver biopsy, as liver enzymes such as alanine aminotransferase (ALT) used, as a serum marker may not be elevated

The functional and structural analysis of a mimetic peptide of human hepatic lipase

Human hepatic lipase (hHL) is bound to the cell surface via heparan sulfate proteoglycans (HPSGs) and hydrolyzes triglycerides and phospholipids within circulating lipoproteins. High-density lipoprotein (HDL) transports excess extrahepatic cholesterol to the liver for excretion. However, small lipid-deficient HDL generated by hHL action has the ability to accept more cholesterol. I hypothesized that a peptide mimicking the cell surface associations of hHL will displace hHL from cell surfaces, increasing its activity in cell culture media. To test this hypothesis, I have recombinantly expressed and purified a tagged mimetic peptide, encompassing the major heparin-binding domain of hHL. Results from in vitro lipase displacement assays showed that the peptide has an ability to displace active HPSG associated lipases. Data from proton nuclear magnetic resonance experiments showed that structural changes occur in the peptide in the presence of heparin. Overall, these data provide a foundation to use mimetic peptides for the displacement of cell surface associated lipases

Androsterone glucuronide to dehydroepiandrosterone sulphate ratio is discriminatory for obese Caucasian women with polycystic ovary syndrome

BACKGROUND: Androsterone glucuronide (ADTG) concentrations have been suggested as a marker of the effects of androgens at the target tissue level. As the mechanism for hyperandrogenemia in obese and nonobese polycystic ovary syndrome (PCOS) may differ, this study compared the different androgen parameters in non-obese compared to obese women with PCOS, and in normal subjects. METHODS: Eleven non-obese and 14 obese women with PCOS were recruited and compared to 11 control women without PCOS. Total testosterone, dehydroepiandrosterone sulphate (DHEAS), ADTG, and androstenedione were analysed using gold standard tandem mass spectrometry, and the free androgen index (FAI) was calculated. RESULTS: Total testosterone, ADTG and androstendione levels did not differ between non-obese (body mass index (BMI) ≤25 kg/m2) and obese PCOS (BMI >25 kg/m2) but all were significantly higher than for controls (p < 0.01). The ADTG to DHEAS ratio was significantly elevated 39 ± 6 (p < 0.01) in obese PCOS in comparison to non-obese PCOS and controls (28 ± 5 and 29 ± 4, respectively). The free androgen index (FAI) and insulin resistance (HOMA-IR) were significantly higher in obese PCOS compared to non-obese PCOS and controls (p < 0.01). DHEAS was significantly higher in the non-obese versus obese PCOS (p < 0.01). All androgen parameters were significantly lower and sex hormone binding globulin (SHBG) significantly higher in normal subjects compared to those with obese and non-obese PCOS. CONCLUSIONS: The ADTG:DHEAS ratio was significantly elevated in obese PCOS compared to non-obese PCOS and controls suggesting that this may be a novel biomarker discriminatory for obese PCOS subjects, perhaps being driven by higher hepatic 5α reductase activity increasing ADTG formation in these women

3-({[(1-Phenyl­eth­yl)sulfan­yl]methane­thio­yl}sulfan­yl)propanoic acid

In the title compound, C12H14O2S3, a chain transfer agent (CTA) used in polymerization, the dihedral angle between the aromatic ring and the CS3 grouping is 84.20 (10)°. In the crystal, carb­oxy­lic acid inversion dimers linked by pairs of O—H⋯O hydrogen bonds generate R 2 2(8) loops

Exploring the Next Frontier for Tobacco Control: Nondaily Smoking among New York City Adults

Objective. Among current smokers, the proportion of Nondaily smokers is increasing. A better understanding of the characteristics and smoking behaviors of Nondaily smokers is needed. Methods. We analyzed data from the New York City (NYC) Community Health Survey to explore Nondaily smoking among NYC adults. Univariate analyses assessed changes in Nondaily smoking over time (2002–2010) and identified unique characteristics of Nondaily smokers; multivariable logistic regression analysis identified correlates of Nondaily smoking in 2010. Results. The proportion of smokers who engage in Nondaily smoking significantly increased between 2002 and 2010, from 31% to 36% (P = 0.05). A larger proportion of Nondaily smokers in 2010 were low income and made tax-avoidant cigarette purchases compared to 2002. Smoking behaviors significantly associated with Nondaily smoking in 2010 included smoking more than one hour after waking (AOR = 8.8, 95% CI (5.38–14.27)); buying “loosies” (AOR = 3.5, 95% CI (1.72–7.08)); attempting to quit (AOR = 2.3, 95% CI (1.36–3.96)). Conclusion. Nondaily smokers have changed over time and have characteristics distinct from daily smokers. Tobacco control efforts should be targeted towards “ready to quit” Nondaily smokers

The moral obligations of trust

Moral obligation, Darwall argues, is irreducibly second personal. So too, McMyler argues, is the reason for belief supplied by testimony and which supports trust. In this paper, I follow Darwall in arguing that the testimony is not second personal ‘all the way down’. However, I go on to argue, this shows that trust is not fully second personal, which in turn shows that moral obligation is equally not second personal ‘all the way down’