ACTA ENDOCRINOLOGICA (BUC)

Background. Genetic variants of the endothelial nitric oxide synthase (eNOS) gene have\r\nbeen reported to be associated with cardiovascular disease. We hypothesized that G894T\r\npolymorphism might trigger many of the endocrine-metabolic changes related to metabolic\r\nsyndrome (MetS).\r\nStudy Design. 148 subjects with MetS and 142 healthy control subjects aged 23-60 years\r\nwere studied. Fasting serum levels of insulin, cortisol, 17-OH Progesterone, DHEA,\r\nandrostendione, IGF1, GH, PRL, CRP, resistin and biochemical profile were evaluated. G894T\r\n(eNOS) polymorphism was assayed by using PCR-RFLP technique.\r\nResults. The frequencies of genotypes and alleles of G894T polymorphism did not deviate\r\nfrom the Hardy-Weinberg equilibrium. In the MetS group the percentages of both GT (51.35 vs.\r\n39.44; OR=2.09; CI=1.27-3.45; p= 0.003) and TT (16.22 vs. 8.45; OR=3.08; CI=1.41-6.74;\r\np=0.003) genotypes and T allele (41.9 vs. 28.2; OR=1.83; CI=1.3- 2.6; p=0.0005) significantly\r\nincreased compared to control group. The G894T polymorphism was more significantly\r\nassociated with the MetS in the presence of cortisol, 17-OH Progesterone, PRL, IGF1 and CRP\r\n(OR= 8.20; 95%CI=2.31-29.08; p=0.001) and significantly stronger in the presence of IGF1,\r\nPRL, 17OHP, resistin and CRP (OR= 10.21; 95%CI=2.42-43.05; p=0.002). The T allele carriers\r\nhad higher values of waist circumference, systolic and diastolic blood pressure, cortisol, 17-OHP,\r\nandrostendione, PRL, resistin and lower values of glucose, HOMA-IR in MetS group; The TT\r\ngenotype carriers had higher values of triglyceride in both control and MetS group.\r\nConclusion. Our results show an interaction between the G894T polymorphism and its\r\nphenotypes in conferring a higher susceptibility to the endocrine changes involved in\r\npathogenesis of MetS suggesting a role of the eNOS gene in the modulation of the molecular\r\nendocrine mechanisms.

Context. In HIV+ patients, several factors related to patient and antiretroviral therapy (ART) could determine early onset of bone mineral density (BMD) disturbances. Objective. Evaluation of bone quality according to gender in patients from the HIV Romanian cohort. Design. A cross-sectional study in “Prof. Dr. Matei Balș” National Institute for Infectious Diseases, Bucharest between 2016-2018. Subject and Methods. We collected data regarding HIV infection, ART history, viral hepatitis co-infections and we calculated patients body mass index (BMI). CD4 cell count, HIV viral load (VL), vitamin-D levels were determined. Dual-energy X-ray absorptiometry (DXA) scans were used to evaluate BMD. Results. We enrolled 97 patients with the median age of 26 years. According to the DXA T-scores, 10 males and 8 females had osteopenia and 4 males and 4 females had osteoporosis. According to Z-scores 2 males and 1 female had osteoporosis. Hip DXA T-scores revealed osteopenia in 6 males and 9 females, whereas T and Z-scores showed osteoporosis in 2 males and 3 females. Lumbar spine (LS) T-score diagnosed osteopenia in 9 males and 6 females, while T and Z-scores revealed osteoporosis in 3 males and females. In males, low T-scores were associated with decreased BMI; low LS DXA Z-scores with low vitamin-D levels; low T and Z-scores and LS-BMD with high VL. Conclusions. Evaluating bone quality in patients with a long history of HIV infection, multiple factors should be taken into account.

Context. Anethum graveolens L. is used in the treatment of numerous diseases. But there is limited data about the Anethum graveolens efficiency in thyroid tissue. Objective. The aim of this study is to assess the functional and histopathological changes in thyroid tissues from rats treated with Anethum graveolens L. extract. Design. This is an experimental animal study and duration of the study was 30 days. Subjects and Methods. Twenty-eight female Wistar Albino rats were divided into four equal groups. A gavage of Anethum graveolens L. extract at 0, 50, 150 and 300 mg/kg/day doses were given to the rats with 1 mL 0.9% NaCl, respectively, for 30 days. Blood was taken at day 0, 15 and 30. fT3, fT4, TSH values and antioxidant efficiency were observed. Also the thyroidectomy tissue was assessed histopathologically. Results. There is no difference observed in the fT3, fT4 and TSH values of groups 1, 2 and 3 at day 1, 15 and 30 (p>0.05); however, in group 4, TSH value decreased on days 15 and 30 when compared to day 1 and the other groups (p<0.05). Also the hypertrophy and thyroid follicular cell hyperplasia were significantly increased in group 4 (p<0.05). There is no difference in antioxidant efficiency in any of the groups (p>0.05). Conclusion. Anethum graveolens L. extract is effective on both the function and the histology of thyroid tissue but it has no effect on antioxidant status.

Introduction. Insulin resistance or dysfunction of pancreatic beta cells represents one of the important worldwide endocrine disease challenges. In fact, vascular endothelial dysfunction (VED) is involved in the pathogenesis of one of the most significant causes of diabetes-induced morbidity; diabetic nephropathy (DN). Asymmetric dimethyl arginine (ADMA) is one among other incriminating mechanisms of VED. The aim of this study was to assess whether ADMA modulation could be achieved by taurine or rosiglitazone, and whether they could improve tubulo-interstitial ischemia and subsequent renal damage in experimental DN in rats. Material and methods. 40 male Wistar rats were randomly assigned into 4 groups: normal saline-injected control, diabetic control induced by intraperitoneal injection of streptozotocin (STZ) (45 mg/kg), and two diabetic groups daily treated orally with rosiglitazone (3 mg/kg) and taurine (500 mg/kg) respectively, for 12 weeks after STZ injection. Results. Both rosiglitazone and taurine treatments significantly decreased fasting blood glucose, renal functions (serum creatinine, blood urea nitrogen, albuminuria), and renal oxidant potential (Malondialdehyde), as well as, tumor necrosis factor-alpha (TNF-α). They also significantly improved renal antioxidant capacity (reduced glutathione) and histopathological changes. Furthermore, taurine significantly diminished serum ADMA, while rosiglitazone showed no significant effect. Conclusion. The present study suggests that the treatment with rosiglitazone or taurine can reduce the progression of renal damage in streptozotocin-induced diabetic nephropathy in rats by different mechanisms. However, reducing ADMA could be a potential therapeutic target.

Autoimmune diseases are a heterogeneous group that involves almost any tissue and organ, a patient could frequently present more than one autoimmune disease. Type 1 diabetes mellitus is frequently associated with other autoimmune diseases in polyglandular autoimmune syndrome. Aim of the study is to evaluate a phenotype of diabetic patients with autoimmune diseases. There is a retrospective study; we analyzed type 1 diabetes inpatients from our department in late 4 years based on clinical records. We state that type 1 diabetes mellitus diagnosis is established based on insulin treatment at onset or less than 1 year from onset. We analyzed the presence of the following autoimmune diseases: Graves&#8217; disease, Hashimoto thyroiditis, autoimmune hypothyroidism, Addison&#8217;s disease, vitiligo, psoriasis, systemic lupus erythematosus, pernicious anemia. We recorded 151 patients with type 1 diabetes mellitus: 91 (60.3%) women. Mean age was 38.4?15.8 years, mean span of type 1 DM was 12 years, mean age at the onset of DM was 26.5 years, and mean BMI was 23.4 kg /m2. Patients were insulin treated with 2 doses of insulin 11.3%, 3 doses of insulin 41.6%, 4 doses of insulin 45%, and insulin pump 2%. 41 patients (27.2%) associated other autoimmune diseases, most frequently being chronic thyroiditis. Type 1 DM preceded autoimmune disease in 60%. Patients that associated autoimmune disease have mean age at the onset of type 1 DM 29.1 years. Mean glycated hemoglobin among patients with autoimmune diseases was 10.1% vs. 9.9% among patients without autoimmune diseases (NS); mean insulin needs were respectively 0.78 u/kgc vs. 0.72 u/kgc (NS). In conclusion, type 1 DM is frequently associated with other autoimmune diseases, patients being mainly women. The most frequent association is Graves&#8217; disease. In over 50% of cases type 1 DM precedes autoimmune disease with several years. Even though more than half of patients were treated with multiple doses of insulin, glycated hemoglobin was high, slightly higher among patients with autoimmune diseases but the differences were not statistically significant.

Published data sustain the involvement of diet on pathogenesis of immune-mediated diseases.\r\nAim. To determine if the high fat diet (HFD), in the absence of obesity, could modulate the altered pulmonary arteries\r\nreactivity associated to allergic lung diseases.\r\nMaterials and Methods. Obese resistant rats were divided into 2 groups: standard chow diet and HFD. Randomly chosen rats from both groups were sensitized against ovalbumin. The histological aspect and reactivity of pulmonary arteries were comparatively assessed. Taking into account the involvement of adipokines on obesity associated vascular reactivity alteration we also studied the vasomotor effects of few adipokines on pulmonary vessels.\r\nResults. Lung histological examination revealed that HFD aggravated the remodelling of pulmonary arteries and\r\ninflammation of lung parenchyma. The HFD amplified the phenylephrine - induced contractions. Angiotensinogen amplified and apelin inhibited the Phe contractile effects on sensitized HFD fed rats.\r\nConclusion.These effects could be at least mediated, by both the alteration of adipokines vasomotor effects and\r\ninflammation associated to pulmonary allergic disease.

Objective. The aim of this study was to evaluate the possible protective effects of MT against gastric oxidative stress and dyslipidemia in streptozotocin (STZ) - induced diabetic rats. Methods. Forty male Wistar rats were randomly divided into five groups: control, diabetic, MT 5 mg/kg+ STZ, MT 10 mg/kg+ STZ and MT 20 mg/kg+ STZ. STZ (60 mg/kg) was intraperitoneally (ip) injected as a single dose for diabetes induction. One week after STZ administration, MT was injected daily as ip for 14 days. The levels of malondialdehyde (MDA), total thiol and glutathione, as well as superoxide dismutase (SOD) and catalase activities were measured in gastric tissue. Serum concentrations of triglycerides (TG), total cholesterol (TC), high density lipoprotein (HDL) and low density lipoprotein (LDL) were also determined. Results. Serum glucose significantly increased in diabetic group compared to control group. STZ induced a significant decrease in gastric tissue levels of total thiol, glutathione, catalase and SOD activities and a significant increase in MDA concentration. In diabetic rats, serum TG, LDL and TC were significantly higher and HDL was significantly lower than in the control group. Treatment of diabetic rats with MT caused a significant increase in gastric total thiol content and glutathione concentration as well as SOD and catalase activities. Gastric MDA concentration and serum LDL, TG and TC were significantly lower in MTtreated groups when compared with diabetic group. Conclusion. These data suggested that MT has a therapeutic effect on gastric oxidative damage and dyslipidemia induced by diabetes that possibly may be due to its antioxidant effects.

Background. It is important to protect recurrent laryngeal nerve (RLN) during thyroid surgery. Thus, intraoperative neuromonitoring (IONM) has got popularity. But, the half life of neuromuscular blocking agents used has a reverse correlation with reliability and effectiveness of IONM. This study aimed to research the effect of Sugammadex Sodium, a specific nemuromuscular blocking agent antagonist, on nerve conduction and IONM. Materials and methods. Twenty patients who underwent thyroidectomy under IONM followed an enhanced NMB recovery protocol-rocuronium 0.6 mg/kg at anesthesia induction and sugammadex 2 mg/kg at the beginning of operation. To prevent laryngeal nerve injury during the surgical procedures, all patients underwent intraoperative monitoring. At the same time, the measurement of TOFWatch acceleromyograph of the adductor pollicis muscle response to ulnar nerve stimulation was performed; recovery was defined as a train-of-four (TOF) ratio ≥ 0.9. Age, sex, recurrent laryngeal nerve transmission speeds prior to and after operation, BMI, duration of surgery, the change in nerve transmission after drug administration and complications were analyzed. Results. The mean age and the mean BMI were 47.6±11.82 years and 28.74±3.20, respectively. The mean operation duration was 52.65±5.51 minutes. There was no difference in either right or left RLN monitoring values before and after surgery. Following the drug injection, the TOF guard measurements on the 1st, 2nd, 3rd and 4th minutes were 23.5±4.90; 69.5±6.86; 88±4.1 and 135.9±10.62, respectively. Conclusion. Neuromuscular blocking antagonist use and monitoring nerve transmission speed with TOFguard can provide a safer resection.

Context. Papillary thyroid carcinoma(PTC)s are the indolent progressive tumours. Survivin is a unique bifunctional protein with cell cycle regulation and apoptosis inhibition. The expression of this protein has been shown to be increased in thyroid tumours correlated with aggressive behavior from well differentiated to anaplastic. Objective. In this study, we aimed to investigate the relationship between immunohistochemically survivin expression and tumour-associated prognostic factors in papillary thyroid carcinomas. Design. In patients with thyroidectomy, we compared the clinicopathological findings and immunohistochemical positivity for survivin. Subjects and Methods. In 109 patients, sex, age, tumour size, histological tumour variant, tumour focality, tumour border pattern, tumour peripheral/intratumoural lymphocytic and stromal response, intraglandular spread, extrathyroideal spread, lymph node metastases, lymphocytic tiroiditis and relationships of these findings with survivin positivity were investigated. Results. When we indicated the tumour size and compared it with survivin expression, tumour size correlates with, survivin expression (p = 0.016). Survivin expression was correlated statistically significant with lymphovascular invasion, without stromal response and with intraglandular extension respectively (p<0.001, p = 0.043, p<0.001). No significant correlation was found between other clinicopathological parameters and survival. Conclusion. Few studies have investigated the relationship of survivin expression with prognosis in thyroid papillary carcinomas and showed that survivin was a poor prognostic marker. If its expression is detected in preoperative cytology smears, it may affects the surgical treatment strategy. When it is detected in the tissue, postoperative radioactive iodine treatment plan may be modified and the need for more aggressive follow-up may be considered.

Metformin, a biguanide, remains the most widely used first-line type 2 diabetes drug. It is generally considered weight-neutral with chronic use and does not increase the risk of hypoglycaemia. Most patients eventually require more than one antihyperglycemic agent to achieve target blood glucose levels. The primary objective of this non-interventional study was to describe and compare the main criteria used by physicians from regular outpatient setting in selecting the add-on therapy in patients with inadequately metformincontrolled type 2 diabetes in 2 time points at 1-year distance by assessment of patient, and/or agent characteristics and/or physician decision. At the end of phase one of the study, the mean duration of type 2 diabetes was 6.8 years. The majority of patients included in the study were overweight (32%) and obese (62%), and presented diabetes complications (59.6%). In 50% of the cases, the major reason for selecting the second-line therapy was related to patient characteristics, while agent characteristics and physician decision were the main categories in 38% and 12%, respectively. Importance to achieve glycemic control and estimated treatment efficacy were selected in 73.9% and 82.4% of patients, calculated as percentage in the respective categories.