ACTA ENDOCRINOLOGICA (BUC)

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.

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The pharmacokinetic characteristics of a compound as well as the immediate consequences of its physicochemical behavior during interactions with biological structures,\r\nrepresent the key issues for its pharmacodynamic profile, starting from the most fundamental global aspects (i.e. central and / or peripheral action) to the most detailed ones (i.e. molecular mechanism of action).\r\nSuccessive metabolic reactions lead to either bioactivation or bioinactivation of themolecular entity. A particular importance is currently assigned to several molecular\r\nphysicochemical descriptors, for instance the polarity degree (mirroring the changes of partition coefficients and of the permeability of biological structures), and emphasizing on distribution and renal excretion rate.\r\nThe active metabolite (9-hydroxy-risperidone) of the atypical antipsychotic agent risperidone has an increased polar character and, consequently, its pharmacokinetic profile is modified compared to the parent drug: especially the penetration through the bood brain barrier and the efflux pump mediated transport were considered. In this context, the kinetic characteristics and their correlation with the pharmacodynamic properties for the two active\r\nentities, as well as the consequences dealing with the antipsychotic efficacy, the safety and efficacy profiles can be anticipated. The present approach critically asseses the available data from literature corroborated with the personal findings over the last years.

Background: Despite a low incidence and prevalence, pheochromocytoma requires a\r\nparticular attention when evaluating hypertensive patients. If undiagnosed, the excessive\r\nand prolonged secretion of catecholamines may cause considerable cardiovascular\r\nmorbidity and mortality. The wide variability of clinical manifestations makes the diagnosis\r\ndifficult, and biochemical confirmation of the disease is mandatory.\r\nCase report: a 32-year-old patient, admitted to hospital with acute left ventricular\r\nfailure caused by severe arterial hypertension associated with the clinical triad (headaches +\r\npalpitations + sweating). The debut of the disease was manifested with a subarachnoid\r\nhaemorrhage. The aetiology remains unclear in the absence of confirmed arterial\r\nhypertension antecedents. In subsequent months he had paroxysmal rhythm abnormalities\r\nassociated with ECG signs of left ventricular hypertrophy considered to be due to nonobstructive\r\nhypertrophic cardiomyopathy. For a period of further three years the patient was\r\nrepeatedly hospitalized for paroxystic elevations of blood pressure not responding to\r\nantihypertensive medication. He developed diabetes mellitus and was started on insulintherapy.\r\nDuring the recent hospitalization, the diagnosis of pheochromocytoma was\r\nconsidered in view of clinical history and the severe hypertension-induced organ damage.\r\nThe diagnosis was confirmed biochemically and a right adrenal tumour was demonstrated\r\non CT. After a successful open adrenalectomy his hypertension was cured.\r\nIn conclusion, the case presented highlights the importance of recognising the symptoms\r\nand clinical signs suggestive of PHEO in order to reach a correct and timely diagnosis.

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.

years because of their cardio-protective and renoprotective properties in diabetes. SGLT-2 inhibitors, when introduced in diabetic patients, may cause euglycemic diabetic ketoacidosis. A 55-year-old woman presented with low-grade fever, vomiting, and lethargy. She was started on dapagliflozin two years back. On workup, she was diagnosed with euglycemic diabetic ketoacidosis (EDKA) and was managed accordingly. She improved clinically while her dapagliflozin was stopped. With a literature search, we have identified 15 case reports of EDKA with dapagliflozin since 2015. There are no standard guidelines regarding the monitoring of patients for this rare but potentially morbid complication. Moreover, the exact mechanism for this is unknown. Various precipitating factors are linked with SGLT-2 inhibitors in promoting EDKA. We recommend that customary plans should comprise educating the patient about this rare complication before commencing medication, close follow-up with serial electrolyte monitoring, and discontinuing medications in the state of infection, dehydration and recent surgery and serious illness requiring hospitalization.