Metabolic syndrome: definitions and controversies

Metabolic syndrome (MetS) is a complex disorder defined by a cluster of interconnected factors that increase the risk of cardiovascular atherosclerotic diseases and diabetes mellitus type 2. Currently, several different definitions of MetS exist, causing substantial confusion as to whether they identify the same individuals or represent a surrogate of risk factors. Recently, a number of other factors besides those traditionally used to define MetS that are also linked to the syndrome have been identified. In this review, we critically consider existing definitions and evolving information, and conclude that there is still a need to develop uniform criteria to define MetS, so as to enable comparisons between different studies and to better identify patients at risk. As the application of the MetS model has not been fully validated in children and adolescents as yet, and because of its alarmingly increasing prevalence in this population, we suggest that diagnosis, prevention and treatment in this age group should better focus on established risk factors rather than the diagnosis of MetS

Central retinal vein occlusion and pseudoexfoliation syndrome

Dimitrios Karagiannis,1 Georgios A Kontadakis,1,2 Nektarios E Klados,2 Ioannis Tsoumpris,1 Artemios S Kandarakis,1 Efstratios A Parikakis,1 Ilias Georgalas,3 Miltiadis K Tsilimbaris21Ophthalmiatreio Eye Hospital of Athens, Athens, Greece; 2Department of Ophthalmology, University Hospital of Heraklion, University of Crete, Heraklion, Greece; 3Department of Ophthalmology, General Hospital of Athens, Athens, Greece Purpose: The purpose of this study was to investigate the existence of pseudoexfoliation syndrome (PXF) as a risk factor for the development of central retinal vein occlusion (CRVO).Methods: This was a retrospective, comparative study of the prevalence of pseudoexfoliation in three groups of patients: 48 patients with CRVO, 164 patients with branch retinal vein occlusion (BRVO), and 70 control patients (70 eyes). All patients were phakic and had no previous diagnosis of glaucoma. Patients were matched in terms of age and systemic hypertension. All patients had normal intraocular pressure (IOP) at presentation (defined as less than or equal to 21 mmHg).Results: In the CRVO group, 14 out of 48 patients were diagnosed as having PXF (29.17%). In the BRVO group, 14 out of 164 patients had PXF (8.5%), and in the control group, six out of 70 patients had PXF (8.6%). Differences of percentage between groups were statistically significant (P<0.001, χ2 test). When comparing patient subgroup with ischemic CRVO with subgroup with non-ischemic CRVO, we found that in the ischemic CRVO group, 13 out of 27 patients were diagnosed as having PXF (48.15%), and in the non-ischemic CRVO group, one out of 21 patients was diagnosed as having PXF (4.7%; P<0.001, χ2 test). The relative odds of having CRVO in patients with PXF versus patients without PXF were 4.406 (confidence interval [CI], 2.03–9.54).Conclusion: PXF and CRVO, especially ischemic, are strongly associated in our study. Our results indicate that PXF might be an independent factor for CRVO, as it is related with CRVO independently from glaucoma.Keywords: pseudoexfoliation, ischemic and non-ischemic central retinal vein occlusion, branch retinal vein occlusion, glaucom

Metformin improves ovarian follicle dynamics by reducing theca cell proliferation and CYP-17 expression in an androgenized rat model

Abstract\ud \ud Background\ud Metformin influences insulin receptor signaling, which might interfere with the proliferation of ovarian follicular structures and steroidogenesis. We hypothesize that reductions in glucose and insulin levels might interfere with CYP-17 expression and histomorphological changes in an androgenized rat model. The aim of this study was to analyze the effect of metformin on CYP-17 expression, follicular dynamics, and proliferative parameters in neonatally androgenized female rats.\ud \ud \ud Methods\ud Thirty-six newborn rats were randomly allocated to the following three groups on the third day of life: control (CG, n = 12), androgenized (GA, n = 12), and androgenized + metformin (GAmet, n = 12). The GA and GAmet animals were administered 0.1 mL of testosterone propionate (1.25 mg/animal) diluted in castor oil (vehicle) in a single dose; the CG rats received a subcutaneous injection of the vehicle in the dorsum. After 90 days, gavage treatment was initiated, distilled water was administered to the CG and GA rats, and metformin (150 mg/kg) was administered to the GAmet animals. The treatment was administered daily for six weeks. Following anesthesia, blood was drawn for biochemical measurements, and the ovaries were removed for histological and immunohistochemical analyses of Ki67, VEGFA and CYP17 expression. The glucose and insulin levels were also measured.\ud \ud \ud Results\ud The comparison of the GA and GAmet animals revealed that metformin decreased the weight as well as the glucose and insulin levels, slowed the proliferation of the theca interna and interstitial cells, as evidenced by Ki-67 and VEGF-A expression, and diminished CYP17 expression in the analyzed ovarian structures. In addition, metformin reduced the number of degenerating follicles and interstitial cells and improved angiogenesis.\ud \ud \ud Conclusion\ud Metformin improves the carbohydrate metabolism, reduces proliferation, and decreases CYP-17 expression in the follicular structures of androgenized rats.This project was funded by São Paulo Research Foundation (FAPESP – Process Number: 2009/54019–9). Pio XI St, 1500. Alto da Lapa. São Paulo/SP-Brazil. Postal Code: 05468–901

High-fat or ethinyl-oestradiol intake during pregnancy increases mammary cancer risk in several generations of offspring

Maternal exposures to environmental factors during pregnancy influence the risk of many chronic adult-onset diseases in the offspring. Here we investigate whether feeding pregnant rats a high-fat (HF)- or ethinyl-oestradiol (EE2)-supplemented diet affects carcinogen-induced mammary cancer risk in daughters, granddaughters and great-granddaughters. We show that mammary tumourigenesis is higher in daughters and granddaughters of HF rat dams and in daughters and great-granddaughters of EE2 rat dams. Outcross experiments suggest that the increase in mammary cancer risk is transmitted to HF granddaughters equally through the female or male germ lines, but it is only transmitted to EE2 granddaughters through the female germ line. The effects of maternal EE2 exposure on offspring's mammary cancer risk are associated with changes in the DNA methylation machinery and methylation patterns in mammary tissue of all three EE2 generations. We conclude that dietary and oestrogenic exposures in pregnancy increase breast cancer risk in multiple generations of offspring, possibly through epigenetic means