ACTA ENDOCRINOLOGICA (BUC)

Context. Persistent inflammation and impaired neovascularization are important contributors to the development of diabetic retinopathy (DR). Gene polymorphisms of adiponectin (APN) were demonstrated to have an important role on the plasma level and activity of adiponectin. APN has anti-inflammatory, anti-diabetic and anti-atherogenic properties. Toll-Like Receptor 4 (TLR4) is a critical mediator of innate immunity. Polymorphisms in TLR-4 gene were shown to be associated with impaired inflammatory response in diabetes. Objective. The aim of the study was to analyze the association of +276G>T variant of APN gene and Asp299Gly and Thr399Ile of TLR-4 gene variants in relationship with T2DM and DR in an Eastern European population group. Design. The distribution of the mutant alleles in 198 T2DM patients with DR and 200 non-T2DM controls was examined. Genomic DNA from T2DM patients and healthy controls genotyped through the use of PCR-RFPL assay. Results. Genotype and allele frequencies of the Asp299Gly and Thr399Ile polymorphisms differed between T2DM patients and non diabetic subjects (P<0.001). Moreover, the presence of the minor alleles of these polymorphisms were significantly identified as protective factors against T2DM, under a dominant model of Fisher’s exact test (χ2=4.988, phi=0.745, OR=0.767, 95% CI=0.602-0.867, P<0.001; respectively χ2=5.254, phi=0.820, OR=0.487, 95% CI=0.211- 0.648, P<0.001). Genotype analysis for the adiponectin 276G>T gene polymorphism yielded no significant association with T2DM, but revealed a borderline significance for the association with DR (χ2=5.632, phi=0.423, OR =1.101, 95% CI=0.887-1.203, P=0.009). Conclusions. We found an association between the TLR4 Asp299Gly and Thr399Ile polymorphisms and protection for DR. The APN genetic polymorphism is not associated with T2DM.

Alzheimer’s disease(AD) is the leading cause of dementia and is characterized by the presence of extensive plaque deposition and neurofibrillary pathology. The aim of the present study was to make an update regarding the influence of estrogens and SERMs on inflammation and on the resolution of inflammation, respectively, focusing on these most important features implicated in the pathophysiology of AD. Several hypothesised mechanisms of action of estrogens and SERM are exposed and also some relevant clinical studies on this subject are analysed. The analyzed studies have a high heterogeneity of preparations used, of administration routes, of the female population included and of the periods of time from the appearance/ induction of menopause to the therapeutic intervention and also of follow-up periods of patients and of the means of evaluating their cognitive decline. One can say that all the ways of pharmacological influence on the membrane or intracellular signalling system associated to estrogens that may have clinical importance in the prevention and possibly in the treatment of AD have not been exhausted. Estrogens with selective ERα or G protein-coupled estrogen receptors (GPER1 or GqMER) effects could be used to influence the resolution of inflammation process, with positive effects on AD evolution.