ACTA ENDOCRINOLOGICA (BUC)

Context. Diverse physiological or pathological events which are stimulated or contributed by HGF/c-Met pathway overlap by processes that play roles in etiopathogenesis of diabetes. Objective. In this study, it was aimed to analyse hepatocyte growth factor (HGF) and its receptor c-Met by immunohistochemistry in the heart and aorta tissues of diabetic and insulin-treated diabetic rats. Subjects and Methods. Accordingly, 21 rats were (equally) divided into three groups: Control (C), Diabetic (D), and Insulin-treated Diabetic (D + I). Rats were treated with Streptozotocin (STZ) (45 mg/kg, i.p.) to induce diabetes. Rats in the control group were given saline once a day for 8 weeks, while rats in the D + I group received 6 U/kg NPH insulin once daily for 8 weeks. The heart and aorta tissues were examined with immunohistochemistry, using antibodies against HGF and c-Met. Results. HGF and c-Met expressions were observed to be increased both in heart and aorta tissues in group D, whereas they decreased in group D+I. Conclusions. As a result, insulin treatment was determined to have a reducing effect on the increased expression of HGF and c-Met in diabetic heart and aorta. According to our results, increased HGF ve c-Met values observed in the myocardium and aorta in diabetes, are shown to increase in parallel to tissue damage and decrease by insulin treatment which is an effective therapy method.

Context. Aromatase is a key enzyme in local estrogen production by androgen conversion, especially in women post-menopause. There have been controversies concerning aromatase localization in breast carcinomas and its association with current histopathological variables. Material and Methods. Using polyclonal antibody immunohistochemistry we assessed (by intensity and percentage scores) the immunolocalization of aromatase in 70 tissue samples, and described particularities within the molecular subtypes of breast cancer. Results. Aromatase was found in all tissue compartments: tumor (95.7%), stroma (58.6%) and adipose tissue (94.3%). Aromatase expression in tumor cells correlated inversely with tumor grading (p=-0.361, p=0.027), and positively with estrogen receptor status (ER, p=0.143, p<0.001). Dividing the study group by intrinsic subtypes, a strongly inversely association between tumor aromatase and grading (p=-0.486, p<0.001), and between stromal aromatase and Ki67-index (p=-0.448, p=0.048) was observed in luminal A breast cancer. Tumor aromatase and ER percentage scores had stronger correlations in luminal B HER2 negative (p=0.632, p=0.002), and positive (p=0.324, p=0.026) tumors. In contrast, in triple negative tumors, a positive association stromal aromatase and Ki67 index (p=- 0.359, p=0.007) was observed. Conclusion. Local aromatase was linked to better tumor differentiation and proliferation in luminal breast subtypes, and not in triple negative cases, suggesting a potential prognostic role of aromatase in breast carcinomas.

Objective. We aimed to investigate whether lifestyle and body fat mass have an impact on the occurence of nonfunctional adrenal incidentalomas (NFAI). Methods. 100 patients with NFAI were included . 50 people constituted the control group. Physical activities of these groups were evaluated (using the International Physical Activity Questionnaire), smoking status was determined, anthropometric measurements were made. Body fat mass, fat percentage, total body water and fat free mass were measured using bioelectrical impedance method. Results. Body mass index (BMI), waist, hip, neck circumference, total body fat percentage and fat mass and smoking rate were found to be statistically higher in the patient group. Physical activities did not differ significantly. When a subgroup with similar age and BMI among was created, waist circumference and total fat mass were again significantly higher in the patient group. There was a significant positive correlation between the size of the adrenal mass and waist, neck circumference, BMI, and cortisol after 1 mg dexamethasone suppression test. Conclusion. The increase in the fat mass may have an impact on the development of NFAI. Although the patients were regarded as nonfunctional, suppressibility of the cortisol decreases as the mass size of the incidentaloma increases.

Context. With more studies investigating effects of high serum lipid levels, new findings are emerging regarding the damage these biomolecules may cause. Aim. In this study we aimed to find a relation between neuropathy and hypertriglyceridemia in patients with metabolic syndrome (MS). Material and methods. One hundred and twenty subjects (Ninety subjects with metabolic syndrome and 30 healthy controls) were included in the study. Subjects with MS were divided into three groups. HbA1C levels of the subjects were < 5.7% in group A, ≥ 5.7% - < 6.5% in group B, and ≥ 6.5% - < 8.0% in group C. Pin-Prick test and Semmes- Weinstein Monofilament were used for neurological examination. Electromyography was performed to patients with neuropathy to support the diagnosis. Results. Neuropathy prevalence was found to be higher in the subjects with metabolic syndrome compared to control group. (9.9 %; 16.65 %; 23.31 % vs. 3.3%; in group A, group B, group C vs. healthy control group respectively) (p=0.003 for group A, p=0.0002 for group B, p=0.0002 for group C). There was an association between triglyceride levels and neuropathy in group C. Conclusion. Patients with MS may have more neuropathy risk than we estimate.

Introduction. Thyroid diseases may cause endothelial dysfunction. Asymmetric dimethylarginine (ADMA) levels in patients with thyroid dysfunction were analyzed by few studies.\r\nAim.We aimed to compare ADMA levels in patients with hyperthyroidism in a cohort free of cardiovascular risk associates such as diabetes or chronic renal failure with further comparison with healthy control subjects.\r\nMaterials and methods. The study took place in Duzce University Medical Faculty, Cardiology and Internal Medicine\r\nDepartment during the year 2010. The study group consisted of patients with hyperthyroidism (overt and subclinical). The patients with renal failure, diabetes and severe\r\nhypertension were excluded.\r\nResults. Mean ADMA level was 1.04 ? 0.43 &#956;mol/L in the hyperthyroid group and 0.68 ? 0.21 &#956;mol/L in the control group (p&#8804;0.001). The comparison of patients with hyperthyroidism according to the etiology (three groups as Graves?, multinodular goiter and thyroiditis) did not show any significant difference.\r\nConclusion. Asymmetric dimethylarginine increases in patients with hyperthyroidism regardless of the etiology.\r\nThe increase of ADMA levels is independent of known major cardiovascular risk factors. It may reflect the possible counteraction of endothelial dysfunction in the pathogenesis of atherosclerosis in hyperthyroidism beyond the known cardiovascular risk factors.

Aims. This study investigated the relationship between proteinuria levels, clinicopathological features, and renal prognoses in Chinese patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN). Methods. Three hundred patients with T2DM and biopsy-proven DN were enrolled. Patients were stratified by 24-h proteinuria levels: Group 1:≤1g/24h); Group 2:1-3g/24h; and Group 3:≥3g/24h. Renal outcomes were defined as having reached end-stage renal disease (ESRD). The proteinuria level’s influence on the renal outcomes was evaluated using Cox regression analysis. Results. Among subgroups stratified by proteinuria levels, systolic blood pressure, serum creatinine, BUN, cholesterol, DR and hypertension incidence, the incidences of patients who progressed to ESRD were the lowest in group 1 (P<0.05). However, eGFR, serum albumin and hemoglobin were highest in group 1. Patients with higher proteinuria levels had much lower five-year renal survival rates. Univariate analyses revealed that higher proteinuria levels were significant clinical predictors of renal prognosis (P<0.05), although they were not independent risk factors for progression to ESRD in the multivariate Cox proportional hazard analysis (P>0.05). Conclusions. The higher the level of proteinuria, the lower the 5-year renal survival rate of DN patients, but there was no significant correlation between proteinuria level and 5-year renal survival rate. Other factors in the proteinuria group may have more significant effects on the 5-year renal survival rate, such as lower baseline eGFR, serum albumin, hemoglobin and higher cholesterol, higher incidences of DR and more severe lesions.

Background and Aim. Ischemia-reperfusion (I/R) injury frequently occurs in different situations. Female sex hormones have a protective function. The purpose of this study was to determine the function of female sexual hormones on the gastric damage induced by I/R in male rats. Methods. Forty (40) Wistar rats were randomized into five groups: intact, ischemia- reperfusion (IR), IR + estradiol (1mg/kg), IR + progesterone (16 mg / kg) and IR + combination of estradiol (1mg / kg) and progesterone (16 mg/ kg). Before the onset of ischemia and before reperfusion all treatments were done by intraperitoneal (IP) injection. After animal anesthesia and laparotomy, celiac artery was occluded for 30 minutes and then circulation was established for 24 hours. Results expressed as mean ± SEM and P <0.05 were considered statistically significant. Results. The Glutathione (GSH) concentration significantly decreased after induction of gastric IR (P<0.001). Estradiol (P<0.001) and combined estradiol and progesterone (P<0.001) significantly increased GSH levels. The myeloperoxidase (MPO) concentration significantly increased after induction of gastric IR (P<0.001). Different treatments significantly reduced MPO levels (P<0.001). The gastric acid concentration significantly increased after induction of gastric IR (P<0.001). Treatment with estradiol, progesterone (P<0.05) and combined estradiol and progesterone (P<0.01) significantly reduced gastric acid levels. Superoxide dismutase (SOD) concentration decreased after induction of gastric IR. The SOD levels were not significant. Conclusion. These data suggested that female sexual steroids have a therapeutic effect on gastrointestinal ischemic disorders by reduction of MPO and gastric acid, and increasing gastric GSH & SOD levels following gastric IR.

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.

Aims. Resistin has been reported to impair the pancreatic beta cells and associated with insulin resistance. MicroRNAs (miRNAs) are short, endogenously produced non-coding ribonucleotides that bind mRNAs and function mainly as negative regulators in mammals. MiRNAs have been implicated in many diseases, including insulin resistance and diabetes. A considerable body of evidence has indicated an important function for miRNAs in insulin secretion. The current study was designed to investigate the effects of miR-494 in the reductions in insulin secretion attributable to resistin. Methods. Insulin secretion was determined by ELISA, and expressions of genes were identified using quantitative RT-PCR (qRT-PCR) or Western blot analysis. Results. Insulin secretion was significantly reduced by resistin. Overexpression of miR-494 inhibited insulin secretion both in diet culture and high glucose medium in MIN6 cell lines. MiR-494 down-regulated the protein level of STXBP5 by pairing with sites in the 3′UTR. Conclusion. miR-494 is involved in the insulin secretion regulated by resistin via its effects on STXBP5 in MIN6 cells.

Vitamin D deficiency and insufficiency are common medical problems worldwide as they\r\nare quite prevalent in both healthy adults and individuals with osteoporosis, hospitalized patients\r\nand free-living and institutionalized elderly. The lack of serum 25-hydroxy-vitamin D (25OHD)\r\nassays standardization, variability of reference population, and the use of different cut-off points\r\nhave produced quite different prevalence reports from epidemiological studies.\r\nWe investigated the vitamin D status (deficiency, insufficiency, sufficiency) in 1048\r\nRomanian postmenopausal women with osteoporosis referred to our clinic for diagnosis and\r\ntreatment in the last three years. Most patients were untreated with osteoporosis drugs and nonsupplemented\r\nwith vitamin D. In our country dietary sources of vitamin D are scarce and there\r\nis no fortification of food with vitamin D. We found a high prevalence of both vitamin D\r\ndeficiency (25OHD < 10 ng/mL) - 22.23% and insufficiency (25OHD=10-30 ng/mL) - 61.26%.\r\nOur study also revealed a high prevalence of low vitamin D when using other cut-offs as reported\r\nin the literature. 83.49% had values lower than 30 ng/mL and 60.97% lower than 20 ng/mL. In\r\nthis study we identified a serum 25OHD concentration of 35 ng/mL above which serum\r\nparathyroid hormone (PTH) concentration attains a plateau at about 35 pg/mL. The relation\r\nbetween serum PTH and 25OHD concentration was non-linear and a log-log diagram showed a\r\nvery weak correlation. The prevalence of secondary hyperparathyroidism was 32.25% in the\r\nwhole population studied. It ranged from 40% in the subgroup of serum 25OHD less than 10\r\nng/mL to less than 15% in patients with 25OHD higher than 30 ng/mL.\r\nIn conclusion, in a representative osteoporosis population from Romania we found a very\r\nhigh prevalence of vitamin D deficiency and insufficiency whatever the cut-off used for\r\ndefinition.