ACTA ENDOCRINOLOGICA (BUC)

Background and Purpose. Fibroblast growth factor 21 (FGF21) has recently been identified as a metabolic regulator, but its physiological role is still not completely known. The aim of this study was to evaluate serum FGF21 levels in an Iranian population with type 2 diabetes. Materials and Methods. This cross-sectional study was conducted in patients with type 2 diabetes. All patients were evaluated for fasting serum levels of glucose, glycated hemoglobin (HbA1c), lipids, urea and creatinine. Participants were divided into two groups with poorly-controlled and wellcontrolled diabetes based on their HbA1c levels. Healthy nondiabetic subjects (matched with patients in terms of age, sex and body mass index [BMI]) were also recruited as control group. Serum FGF21 concentrations were determined in all subjects using ELISA. Results. Of the evaluated 141 subjects, 49 (34.8%) were categorized as having well-controlled diabetes, 66 (46.8%) had poorly-controlled diabetes, and there were 26 subjects in the normal control group. Mean serum FGF-21 concentration was 337.89±283.67 ng/L in the diabetic group and 237.25±43.22 ng/mL in the non-diabetic group (p<0.001). Mean serum FGF21 level was 237.25 ± 43.22 ng/mL in the control group, 309.81 ± 301.68 ng/mL in the well-controlled diabetic group, and 358.73 ± 269.98 ng/mL in the poorly controlled diabetic group. Serum FGF21 level in the poorly controlled diabetic group was significantly higher than that in the well-controlled diabetic and the healthy control groups (p=0.02) but there was no significant difference between the well-controlled and healthy groups. There was no significant association between serum FGF21 levels with lipid levels, presence of diabetic complications and BMI (p > 0.05). Conclusions. The present results suggested an association between elevated serum levels of FGF21 and poor control of diabetes. Future studies are warranted to elucidate the prognostic role of these elevated levels of FGF21 in diabetic subjects.

Background. Type 1 diabetes mellitus is a common disorder which causes a variety of complications such as cognitive deficits in central nervous system. Auditory P300 event related potential is a wellestablished neurophysiologic approach in the assessment of cognitive performance. In this study, we aimed to evaluate the cognitive performance in insulin dependent diabetic patients by auditory event related potentials. Methods. In this descriptive analytical and non-interventional study, auditory P300 event related potential was measured in oddball paradigm by using two tone burst stimuli (1000 & 2000 Hz) on 25 diabetic patients and 25 age, education and sex matched healthy controls, with mean age 28.76±4.1 in patients and 29.68±3.6 in controls. Results. The mean P300 latency of the diabetic patients was significantly prolonged and the mean P300 amplitude of the diabetic patients was significantly lower when compared with that of controls at all electrode sites (p<0.01). Also there was a strong correlation between P300 latency and glucose level, HbA1c and diabetes duration (p<0.01). Conclusion. Auditory information processing is slower and the speed of information categorizing is lower in diabetic patients than in controls.

The nuclear receptor coding PPARγ2 (PEROXISOME PROLIFERATORACTIVATED RECEPTOR-GAMMA; *601487) gene influences the lipid and carbohydrate metabolism via multiple pathways and is a candidate for the metabolic syndrome. In this paper we studied the relationship of the CCG (Pro) → GCG (Ala) polymorphism of the gene with the metabolic syndrome diagnosed according to the criteria recommended by the International Diabetes Federation (IDF) in 2005, in a population from central Romania. We have carried out a case-control study on 144 patients and 73 control subjects. Routine biochemical assays have been carried out, fasting insulinemia was measured by ELISA, and insulin sensitivity was assessed by calculating the HOMA and QUICKI indices. Genetic analysis was done by PCR followed by digestion with the restriction enzyme BstU I. The results show that the Pro12 allele had a higher frequency in the group of patients as compared to the healthy controls (76 vs. 65.7%, p<0.05). The risk for developing the metabolic syndrome in the presence of the Pro12 allele in a homozygous combination was found to be low but statistically significant (PP vs. PA + AA: OR = 1.98, CI 95% 1.04 -3.78, p = 0.046). In conclusion, in the local population, the Pro12 allele of the PPARG2 gene seems to contribute to the hereditary predisposition of the metabolic syndrome diagnosed according to the recommendations of the IDF, most likely as part of a polygenic system. Probably the absence of the protective Ala12 allele increases the risk for developing the disease.

Context. Vitamin D is a steroid hormone that acts by binding to the vitamin D receptor (VDR) found in many tissues. According to the long-term mechanism, vitamin D causes the proliferation and differentiation of muscle cells by gene transcription. Objective. We aimed to evaluate the relationship between muscle strength and serum vitamin D levels in elderly men. Design. Cross-sectional study. Subjects and Methods. Male patients over age 50 were included in the study. Study population was divided into 2 groups with handgrip strength according to body mass index, either as subjects with weak or with normal handgrip strength test (HGST). Vitamin D levels and other variables compared between weak and normal groups. Results. Vitamin D level of weak and normal groups were 7.5 (3-19.9) μg/L, and 11.6 (11.6-34.9) μg/L, which means significant reduced vitamin D levels in weakness group (p=0.01). Vitamin D levels were significantly correlated with HGST levels (r:0.362, p=0.001). Vitamin D levels were found to be an independent predictor of weakness according to HGST in logistic regression analysis (OR: 0.453, 95% Cl:0.138-0.769, p=0.05). Conclusions. Low vitamin D level is an independent risk factor for muscle weakness in men aged more than 50 years. Therefore, vitamin D levels should be screened and early replacement should be initiated for the sake of improvement of muscle strength in elderly subjects that vulnerable for frailty.

Background. The high recurrence rate and low survival rate of ovarian cancer (OC) patients are closely related to an anoxic environment. We aim to study the mechanism of long non-coding RNA (lncRNA) HOXA transcript at the distal tip (HOTTIP) on hypoxia ovarian cancer cells (OCC) and its mechanism was investigated. Methods. Knockdown and overexpression of HOTTIP in human OCC (SKOV-3, OVCAR3) were performed. The expression levels of HOTTIP and HIF- 1α were monitored by qRT-PCR and WB. Transwell was conducted to validate the cell migration and invasion. ELISA was performed to calculate VEGF concentration in cells. Cell viability was monitored by CCK-8. Cell apoptosis and cycle were tested by flow cytometry. RNA pull-down was used to analyze the interaction between HIF-1α and HOTTIP. Results. HOTTIP was highly expressed in OCC. After HOTTIP knockdown, HIF-1α expression and VEGF concentration in OCC were decreased. Cell migration, invasion, and cell viability were decreased. Cell apoptosis rate and G0/G1 phase cells were increased. RNA pull-down indicated a direct interaction between HIF-1α and HOTTIP. Conclusions. HOTTIP formed a positive feedback loop with HIF-1α to promote the development and metastasis of hypoxia ovarian cancer. This study provided theoretical support for the development of new OC treatment strategies.

Methods. Ninety Wistar male rats were used in this study. Type 1 diabetes was induced by i.p injection of 50 mg/kg of streptozotocin in all animals. After 42 days of treatment with testosterone (2mg/kg/day) or voluntary exercise alone or in combination, the heart of the rats has been removed and MicroRNA was extracted from the heart using miRCURYTM RNA isolation kit. Results. Our results showed that either testosterone or exercise increased miRNA-126 expression levels in the heart of diabetic rats. Treatment of diabetic rats with testosterone and exercise at the same time had a synergistic effect on miRNA-126 levels in the heart. Furthermore, in castrated diabetes group, miRNA-126 levels were significantly decreased in heart, whereas either testosterone treatment or exercise training enhanced expression of this miRNA. Also, simultaneous treatment of castrated diabetic rats with testosterone and exercise had an additive effect on miRNA-126 expression levels. Conclusion. This study showed that testosterone and exercise promote an increase in the expression of miRNA-126 in the heart tissue and this may be related to cardiac angiogenesis. These results may indicate that testosterone and exercise can help to prevent progression of diabetic cardiomyopathy due to impaired angiogenesis in the heart.

Background: Hereditary Haemorrhagic Telangiectasia (the Rendu-Osler-Weber syndrome) is a relatively common, underrecognized autosomal dominant disorder that results from multisystem vascular dysplasia. It makes vascular walls vulnerable to trauma and rupture, causing telangiectases and\r\narteriovenous malformations of skin, mucosa and viscera. It is clinically characterized by recurrent epistaxis, telangiectasia lesions on the face, hands and oral cavity, visceral arteriovenous malformations and positive family history. Epistaxis is often the first manifestation associated with haematologic, neurologic, pulmonary, dermatologic and gastrointestinal complications.\r\nCase report: a patient came to our observation presenting recurrent epistaxis with a severe iron deficiency anaemia and hypoparathyroidism. Genetic, laboratory and imaging findings were compatible with the presence of Rendu-Osler-Weber syndrome associated to a form of idiopathic hypoparathyroidism that could find its physiopathological origin in a consequence of an autoimmune process affecting\r\nparathyroids.

The debates on the quality of oocytes in PCOS patients are still heated and controversy is very intense, with a wide\r\nspectrum of variations proposed. The present study aims at analyzing the main factors altered in the economy of PCOS\r\npathogenesis, mainly those involved in the folliculogenesis dysfunction, and, also, to evaluate their potentially detrimental role upon oocyte quality.\r\nIndividual elimination of the more prominent follicular factors, at least through deviation from the normal, as compared to the degree of oocyte maturation did not manage to be cleared in unequivocal terms for any of them. Most interestingly, the spectrum of answers varied from\r\nprofoundly modified values to the absence of any differences whatsoever, inevitably leading, as sole functional conclusion, to assuming the extremely heterogeneous\r\ncharacter of this affection.

Background. There are few cases of methimazole induced hepatitis. The mechanism is probably related to the fact that it is a hepatic- metabolised drug. Objective. To demonstrate the fact that an acute cholestatic hepatitis can be triggered by methimazole. Design. While dealing with a major cholestatic syndrome with cytolysis, we performed the following steps: correct and complete history, serum detection of acute viral hepatitis, an autoimmune cause and finally liver biopsy. Subjects and Methods. We present the case of an 80 year old woman, with a history of hyperthyroidism, in treatment with Methimazole. After a month, the patient developed jaundice, for which she was admitted to our clinic. On admission she presented an important cholestatic syndrome, with elevated transaminases (5 times normal). Results. None of the laboratory tests indicated a possible viral infection or autoimmune disease. Abdominal ultrasound revealed no possible obstruction of the biliary system. Ultimately we performed a liver biopsy, which revealed inflammatory infiltration and cholestasis. Conclusion. We conclude that the hepatitis was induced by methimazole. Corticotherapy was initiated, with a relatively slow but favourable evolution. I131- Radiation therapy was elected for the treatment of hyperthyroidism.

Context. Chronic unpredictable mild stress (CUMS) has been widely shown to impact neurological disorders. Recently, growing evidence suggests that CUMS may also contribute to the development of metabolic conditions such as diabetes mellitus. Objective. This study aimed to investigate blood glucose levels and histopathological and immunohistochemical changes in the endocrine pancreas in an experimental rat model of CUMS, as well as the potential protective effects of vortioxetine (VOR) treatment. Subjects and methods. A total of 28 rats were divided into four groups. The CUMS group was exposed to random stressors once daily for six weeks. Rats in the VOR and CUMS+VOR groups received VOR treatment. The VOR and control groups were housed separately, without exposure to CUMS. At the end of the experiment, blood and pancreatic tissue samples were collected from all rats. Results. Blood glucose levels were elevated in the CUMS group compared to the other groups. Histopathological analysis revealed a reduction in insulin, amylin, and insulin receptor expression, along with a slight increase in glucagon expression and a small number of necrotic cells in the CUMS group. VOR treatment improved all these parameters. Conclusions. Our findings suggested that CUMS may contribute to endocrine pancreatic damage resembling diabetes mellitus, while VOR treatment may mitigate this effect.