ACTA ENDOCRINOLOGICA (BUC)

Objective. The aim of the study was to investigate the role of Hepatocyte Growth Factor (HGF)/c-Met pathway in testicular damage provoked by streptozotocin (STZ)- induced diabetes and the effects of insulin treatment on the HGF/c-Met pathway. Methods. Total 21 paraffin-embedded testicular tissues of control (n=7), streptozotocin (STZ)-induced diabetic (n=7) and insulin-treated diabetic (n=7) Wistar albino rats were used in this study. Testicular damage was examined histologically and by Johnsen’s score was also evaluated. Immunohistochemical stainings of HGF and c-Met were analysed by using antibodies against HGF and c-Met. Results. We found the degeneration in seminiferous tubule epithelium and disorganization of spermatogenetic cell series in testis tissues of diabetic rats. We also determined decrease both in seminiferous tubule diameter and Johnsen’s scores in diabetic group. The expressions of HGF and c-Met in seminiferous tubule epithelium and in spermatogenic cells (especially spermatocytes and spermatids) were significantly increased in diabetic rats compared to those of control. Insulin treatment significantly reduced the diabetes-induced morphological changes and HGF/c-Met over expressions in the diabetic rat testis. Conclusion. HGF/c-Met pathway might have a role in diabetes- induced testicular damage. Drugs acting on this pathway might be effective to prevent or delay the testicular damage induced by diabetes.

Hypothalamic kisspeptin signaling has been recently observed to correlate with seasonal breeding in free ranging male rhesus monkeys. Recent evidence also suggests that excitatory and inhibitory amino acid neurotransmitters contribute in regulation of kisspeptin neurons. Objective. The present study was focused on analyzing the interplay of Kiss1 neurons with afferent excitatory and inhibitory signals in the brain of male rhesus monkeys during the breeding and non breeding seasons. We hypothesized that: kisspeptin stimulation may occur due to the increase in N-methyl-D,L-aspartate (NMDA) dependant excitatory inputs and decrease in inhibitory γ-aminobutyric acid (GABA) based cues during the breeding season Materials and Methods. Messenger ribonucleic acid (mRNA) was extracted from the medio basal hypothalamus (MBH) of five free ranging adult male rhesus monkeys (Macaca mulatta) during the breeding season (n=3; October; plasma testosterone levels: 26.15±2.64 nmol/L; testicular volume: 69.00 ± 0.57 ml); and the non-breeding season (n=2; July; plasma testosterone levels: 4.09±1.64 nmol/L; testicular volume: 12.88±0.31 ml). Real time polymerase chain reaction (RT-PCR) was used to quantify the levels of Kiss1, Kiss1r, NR1 and glutamic acid decarboxylase (GAD67) mRNA, relative to glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Results. Significantly high (p<0.05) expression of Kiss1, Kiss1r and NR1 mRNA and low (p<0.05) expression of GAD67 mRNA in the hypothalamus were found to be in synchrony with the breeding season. Conclusion. Based on correlative gene expression changes in the adult male monkey hypothalamus we suggest that in higher primates increased kisspeptin signaling during breeding season may be entrained by an increase in NMDA excitatory inputs; while decreased kisspeptin signaling during the non-breeding season may be driven by an increase in GABA based inhibitory cues.

The determination of cardiac peptides at rest and during exercise stress testing (ET) represents a useful tool for the diagnosis of heart failure patients, but their usefulness in isolated LV diastolic dysfunction was less studied until now.\r\nAim. The aim of this study is to compare the effect of ET upon cardiac peptides in patients with left ventricular systolic and diastolic dysfunction.\r\nMethods. There were studied 101 heart failure patients, 58 with systolic LV dysfunction (LVEF 37.8%) and 43 patients with isolated LV diastolic dysfunction, mainly with hypertension (31 cases). All patients were submitted to a symptom-limited ET on cycloergometer, blood samples being obtained before ET and at peak effort. The plasmatic levels of N terminal pro brain-type natriuretic peptide (NT-proBNP) were determined using ELISA method (n.v. <250 fmol/ml). The systolic and diastolic LV functions were determined by echo-Doppler, according to ESC guidelines.\r\nResults. The results showed that the rest NT-proBNP values were increased in patients with LV systolic dysfunction (640?220 fmol/ml) in comparison with diastolic dysfunction (419 ?120 fmol/ml), p<0.01. At peak effort NT-proBNP increased to 790?242 fmol/ml (23%) in patients with systolic dysfunction (p<0.04) and to 490.2?179 fmol/ml (17%) in patients with diastolic dysfunction (p= NS). There was a close relationship between rest and exercise NT-proBNP values in both systolic (r=0.99, p< 0.05) and diastolic (r=0.72) LV dysfunction. \r\nIn conclusion, in heart failure patients with both systolic and diastolic LV dysfunction, NT-proBNP is increased at rest and during exercise, the increase being significant for patients with LV systolic dysfunction, probably in relationship with more important hemodynamic abnormalities.

A study was performed on the basis of multiple-choice questionnaires applied to a lot of 96 pupils in the forms 9 to 11 at a high-school in the city of Suceava. The questionnaires of 96 de respondents were analysed ? 42 teenage boys (13 from the rural environment, 29 from the urban environment) and 54 teenage girls (19 from the rural environment and 35 from the urban environment). The objectives of the questions were: clarifying the relationships between the teenager and the social and family environment, affiliation to the reference group, knowledge and attitudes concerning the various aspects of sex life: the affective component, the start of sexual activity, notions about contraception and STD-s, the teenagers? attitude concerning the introduction of sex education in school. Most of the teenagers have an optimistic projection on the society?s permissive mentality concerning them and they enjoy a favourable family climate. Affiliation to the peer group, as a reference group, is based on fundamentally positive criteria and moral values and less based on professional interests. Love is perceived in an ideal manner, especially by teenage girls. The optimal age for becoming sexually active is declared as being 16-18 by most of the boys and 19-21 by most of the girls. The notions about contraception have a general character, and their practical application is more frequent with the boys than with the girls. The notions about sexually transmitted diseases, risk and prevention, are slightly better in boys than in girls. The main sources of information the teenagers have about their own sexuality are the media, more than the family and the educators. Although most of the teenagers agree with the need to have sex education in school, they could not offer solutions on the practical ways of delivering this education.

Introduction. Primary hyperparathyroidism is diagnosed earlier and more frequently with the introduction of routine serum calcium measurements. In literature, it is shown that mortality and morbidity decrease after parathyroidectomy. In our study, we aimed to determine the effect of parathyroidectomy on oxidative stress. Materials and Methods. The results of 41 patients who underwent parathyroidectomy for primary hyperparathyroidism between March 2018 and end of December 2018 were evaluated prospectively. Total antioxidant capacity (TAC), superoxide dismutase (SOD), thiobarbituric acid reactive substances (TBARS), 8-hydroxy- 2’-deoxyguanosine (8-OHdG), malondialdehyde (MDA), parathyroid hormone, calcium and albumin were measured before and after parathyroidectomy. Results. The mean age of the patients in the study was 45 ± 13.1 years (age range: 18-76 years). The female/ male ratio was 32/9. Postoperative values of 8OHdG, MDA and SOD 1 were significantly lower than preoperative values (p <0.05). There was no significant difference between preoperative and postoperative TAC and TBARS values. Conclusion. Oxidative stress decreased in patients with primary hyperparathyroidism after parathyroidectomy. Randomized prospective studies are needed to show the relationship between biochemical and clinical parameters in order to see the clinical reflection of the study.

Context. In obesity, the infiltration of leukocytes into adipose tissue seems to play a key role in the development of inflammation and insulin resistance. Over-expression of adipophilin (ADPH) in adipose tissue, a protein which regulates lipid droplet structure and formation, has been reported in some studies. Objective. To investigate the role of ADPH 129- 137 as a target for CD8+ T-cells in PBMCs of patients with obesity. Subjects and Methods. PBMCs were obtained from 9 non-diabetic obese patients and 11 healthy subjects expressing the HLA-A0201 molecule. The ELISPOT assay used to monitor the presence of IFN-γ producing CD8+ T-cells against a HLA class I-restricted epitope derived from Adipophilin (ADPH 129-137) and two control peptides: Flu MP58-66 and Melan-A27-35. Results. The outcomes showed no significant difference between patient group and healthy donors in response to ADPH 129-137. Conclusion. These results demonstrated that ADPH 129-137 peptide possibly does not act as an autoantigen in patients with obesity.

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.

Introduction. The recall rate in congenital hypothyroidism (CH) newborn screening programs depends on several factors such as primary screening strategy, sample collection guidelines, and cut-off. A recall rate of 0.05% is recommended but recall rates of 0.01-13% are reported worldwide. Objective. The aim of the study was to assess the recall rate in association with the age of the newborn at sample collection and with a lower cut-off. Design. This was a retrospective correlational study concerning TSH results in CH screening program. Subjects and methods. All newborns from a tertiary center in Targu Mures, Romania between 2013-2018 were included. Four groups were created and a correlation test between TSH median value and age in days was performed. The recall rate was calculated using three cut-off levels for 8182 TSH results performed in 2018. Results. 90% of the DBS were collected in days 3-5 after birth and 1/79 live births from this group had TSH above the lower cut-off used (10 mUI/L). 2% of the samples were collected in less than 48 hours after birth and 1/21 live birth from this group had TSH > 10 mUI/L. The recall rate in our center in 2018 was 0.08%, higher than the recommended rate of 0.05%. With the cut-off value recommended by the Health Ministry a 0.03% recall rate was obtained. Conclusions. Sample collection in less than 48 hours increases the recall rate in CH screening with TSH primary testing strategy. A lower cut-off raises the recall rate with a higher rate of false-positive cases (94.12%) but with 100% negative predictive value.

Objective. The association between the development of diabetic kidney disease (DKD) and the Triglyceride-glucose (TyG) index, a surrogate marker of IR was barely investigated. We studied the role of TyG index in determining the risk of microalbuminuria before grade 3 chronic kidney disease in type 2 diabetes. Subjects and Methods. This is a cross-sectional study including 365 patients with type 2 diabetes evaluated in the outpatient clinics of a tertiary center. Patients with febrile illness, obstructive uropathy, severe heart failure, stroke, non-diabetic renal disease, liver disease, malignant disease, autoimmune disease, patients with e-GFR < 60 mL/ min/1.73 m2, and pregnant patients were excluded. Results. There was more severe insulin resistance in patients with microalbuminuria, as indicated by the TyG index (P = 0.004). Patients with microalbuminuria had a higher mean TyG index than normoalbuminuric patients (p = 0.035). The TyG index positively correlated with the urine albumin/creatinine ratio (r = 0.223, P < 0.001) and was independently associated with DKD in regression analyses. The optimal cut-off point of the TyG index was defined as > 9.66. Conclusion. The present study showed that higher TyG index levels were associated with increased risk of micro-and macroalbuminuria in type 2 diabetic patients.