ACTA ENDOCRINOLOGICA (BUC)

Context. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a novel biomarker for cardiovascular diseases (CVD) risk estimation with high specificity for vascular inflammation. Few studies have investigated Lp-PLA2 levels in patients with metabolic syndrome (MetS) and obstructive sleep apnea syndrome (OSAS). Objective. This study aimed to evaluate the role of Lp-PLA2 levels as a marker of vascular inflammation that contributes to cardiometabolic dysfunction in patients with MetS and OSAS. Design. This is a prospective case-control study. Subjects and Methods. 83 men were enrolled. Following anthropometric measurements, laboratory analysis and overnight sleep study, patients were divided into three groups: MetS, OSAS with/without MetS. Serum Lp-PLA2 levels were determined by ELISA method. Results. Serum Lp-PLA2 levels were statistically significant among the three groups and were higher in OSAS with MetS group than those without MetS. A significant positive relationship between increased Lp-PLA2 level and CRP (C-reactive protein) and apnea–hypopnea index (AHI) was found. Average oxygen saturation (AvO2) and the lowest oxygen saturation were negatively correlated with Lp-PLA2. The number of desaturation events, oxygen desaturation index, AvO2, AHI and CRP were significant predictors of Lp-PLA2. Conclusions. Lp-PLA2 levels are associated with OSAS severity and might play an important role in predicting CVD in OSAS with/without MetS

Objective. Metabolic syndrome (MetS) is a metabolic condition with high prevalence worldwide. This study aims to examine the relationship between serum concentrations of gastrointestinal hormones such as cholecystokinin (CCK), ghrelin, peptide YY (PYY), and high sensitive C-reactive protein (hs-CRP) and the ingredients of MetS in obese population. Subjects and Methods. This case-control study included 40 obese subjects (20 with MetS and 20 BMI and age-matched control individuals). The age range of the participants was 20-50 years and the participants’ anthropometric characteristics were measured. Serum lipids and the concentrations of oxidized low density lipoprotein (Ox-LDL), insulin, hs-CRP, CCK, PYY, and ghrelin were assessed with commercial ELISA kits. Results. Serum levels of hs-CRP, total cholesterol (TC) and triglycerides (TG) in patients with MetS were significantly higher while CCK and insulin concentrations were higher in obese non- MetS group (P <0.05). PYY had a negative association with waist circumference (WC) and high density lipoprotein cholesterol (HDL-C) and ghrelin had a positive association with systolic blood pressure (SBP) and TC in obese control group (P < 0.05). In obese patients with MetS, hs-CRP had a strong positive association with TG. Conclusion. The current study revealed the possible role of hs-CRP and several GI- hormones in the pathogenesis of obesity-associated diseases and MetS. Additional works are needed to elucidate the possible underlying mechanisms and clarify several controversies in this issue.

Background. Fine-needle aspiration biopsy (FNAB) is the most accurate diagnostic method to assess the malignancy risk of thyroid nodules. However, nondiagnostic results may delay diagnosis, cause unnecessary interventions, and distress patients. Aim. We aimed to determine whether a correlation exists between patients’ situational anxiety, pain perception and non-diagnostic cytology results. Methods. The prospective study included patients who underwent thyroid FNAB at the Endocrinology Clinic of Sultan Abdulhamid Training and Research Hospital between 11/2022 and 02/2023. The State-Trait Anxiety Inventory (STAI) questionnaire and visual analogue scale (VAS) assessed situational anxiety and pain in patients undergoing biopsy procedures. We evaluated whether the STAI-S and VAS score is related to non-diagnostic results. Results. Of the 119 patients included in the study, 98 were female, and 21 were male. 25 (21%) nodules were non-diagnostic. The patients' mean STAI-S score before the biopsy was 47.31±12.37, and the mean VAS score after the thyroid biopsy was 2.57±1.51. A statistically significant relation was found between the patient's STAI-S score and VAS score and the cytology result of non-diagnostic (p= 0.001 and p=0.008). In univariate logistic regression, high pre-procedural anxiety (OR:3.09, 95% CI:1.07-8.94, P =0.037) and VAS score (OR:1.57, 95% CI: 1.17-2.10, P =0.002) were associated with non-diagnostic cytology. In multivariate logistic regression analysis, VAS score (OR: 1.59, 95% CI: 1.07-2.34, p=0.019) was still an independent factor related to specimen adequacy. Conclusions. Anxiety level and pain perception during FNAB may be considered risk factors for nondiagnostic cytology. Thus, reducing anxiety and pain may decrease the incidence of non-diagnostic outcomes.

Purpose. In this study, we aimed to investigate the relationship between hypothyroidism and sterile inflammation in rat heart tissue. Methods. Groups; control group (fed with standard rat chow diet and tab water) and the hypothyroid group (fed with a standard rat chow diet and tap water containing 0.05% 6-n-propyl-2-thiouracil for 6-weeks). At the end of the experiment, histopathologic examination was performed. The T3, T4, TSH and myocardial malondialdehyde (MDA) measurements were performed with an ELISA kit. TUNEL assay was performed to demonstrate apoptosis. Sterile inflammation markers, caspase-1 and NLRP3, were investigated by immunohistochemistry and western blot. Results. In histopathological examination, we observed leukocyte infiltration, myocardial atrophy, pyknotic nucleated cells and cytoplasmic vacuolization in hypothyroid group whereas the control group showed normal structure. MDA levels in myocardial tissue were significantly high in hypothyroid group when compared to the control group (P<0.05). Myocardial apoptosis increased in hypothyroid group when compared to the control group. NLRP3 and caspase-1 immunoreactivity was higher in the hypothyroid group. In ELISA results, we found significantly higher level of TSH and lower levels of T3 and T4 in hypothyroid group when compared to the control group. Conclusion. Hypothyroidism increased oxidative stress, and caused inflammatory alterations in cardiac tissue. In addition, our study also suggested that thyroid hormone deficiency would increase the amounts of cardiac NLRP3 and caspase-1 protein, which indicates that hypothyroidism exerts its destructive effects through sterile inflammation. Elucidation of sterile inflammation-associated pathways may produce promising results in the treatment of hypothyroidism-induced cardiac damage.

Background. Early prediction of anticancer therapy cardiotoxicity is essential for applying proper preventive and supporting therapeutic strategies. Objective. To evaluate plasma N-terminal fragment of pro-brain natriuretic peptide(NT-proBNP) related to cardiac dysfunction assessed by transthoracic 2 D echocardiography (2D-TTE) in patients with cancer and early onset asymptomatic anthracycline-induced cardiomyopathy(AIC). Methods. Prospective study of 68 patients with cancer treated with anthracyclines, followed up for 6 months. Diagnosis of AIC was set at 6 months by decreasing of left ventricular ejection fraction(LVEF) below 50% or with more than 10 units or 20% from baseline. NT-proBNP and 2D-TTE were assessed at enrollment, and thereafter at 3 and 6 months. Results. Fifteen(22.1%) patients developed AIC at 6 months of anthracycline treatment (group 1), and 53(77.95%) patients did not evolve with AIC (group 2). At 3 months, in patients from group 1 NT pro-BNP was significantly higher compared to group 2 [121.0 (119.8;140.8) pg/mL vs. 97.7(75.5;111.7) pg/mL, P=0.0001, values expressed as median (25th; 75th percentiles)]. Left ventricular(LV) diastolic dysfunction was significantly more frequent in group 1(93.3%) vs. group 2(37.7%), P=0.0002. NT-proBNP at 3 months proved accurate in predicting asymptomatic AIC at 6 months [area under the receiver operating characteristic curve(AUC)=0.845, 95%Confidence Interval(CI): 0.735-0.954, P=0.0001]. Newinstalled diastolic dysfunction at 3 months had a sensitivity of 60 %, a specificity of 77% in predicting AIC at 6 months. NT-proBNP assessed at 3 months above a cut-off=118.5pg/ mL was an independent predictor of AIC at 6 months. Conclusions. Plasma NT-proBNP at 3 months of anthracycline therapy proved to be an early independent predictor of asymptomatic anthracycline-induced cardiomyopathy.

Though increased BMI represents a risk factor for developing heart failure, in heart failure (HF) patients it paradoxically increases survival. This effect was not\r\nstudied in relationship with BNP and ACE mutations. Objective. To investigate the relationship between BNP fragment (8-29) plasmatic level, ACE I/D polymorphism and BMI in patients with chronic congestive heart failure. Methods. We studied 50 patients with HF, NYHA III and IV, mean age 64.96?13.24 years, 21 patients with BMI &#8805;30 kg/m2 vs 29 patients with BMI<30 kg/m2. BMI, ACE polymorphism,\r\nthe plasmatic levels of BNP fragment (8-29) were determined.\r\nResults. Mean plasmatic BNP fragment (8-29) level was\r\n1891.02?1008.06 pg/mL, mean BMI value 29.09?7.59 kg/m?, with a negative correlation between the two parameters (r=-\r\n0.46), stronger in women (r=-0.79 vs. r=-0.32 in men). Significant greater value of BNP fragment (8-29) was registered in nonobese patients (2130.77?866.58 pg/mL vs. 1547.765?1135.744pg/mL, p<0.05). The distribution of ACE mutation was: DD allele 36%, II allele 24%, and ID allele 40%. In all three groups, the patients with BMI &#8805;\r\n30kg/m2 presented lower values of BNP fragment (8-29) levels.\r\nConclusion. In HF patients, there was an inverse correlation between BNP value and BMI, obese patients having lower BNP fragment (8-29) values, no matter the ACE\r\npolymorphism.

Context. The relationship between life changes and glycemic control in children with type 1 diabetes during the pandemic period was examined. Objective. We aimed to investigate the effect of the pandemic period on 66 children (aged 5-18 years) with type 1 diabetes using scales evaluating family functionality, nutritional habits, adherence to treatment and depression status. Design. It is a cross-sectional clinical and laboratory study using certain scales for its descriptive features. Subjects and Methods. Demographic characteristics, anthropometric measurements, laboratory investigations were evaluated. Family functionality of the patients were evaluated with Smilkstein’s family APGAR scale, motivation and knowledge levels were evaluated with the 6-item Morisky medication adherence scale (MMAS-6), nutritional habits were evaluated with the Mediterranean diet quality index (KIDMED), and depression status was evaluated with the children depression inventory (CDI). Results. The mean HbA1c level increased significantly in the first year of the pandemic compared to the onset of the pandemic period (8.5% vs. 8.9%, p: 0.003). In the responses to these scales, children with diabetes have high family functionality (89.4%), high motivation (90.9%) and high knowledge level about adherence to treatment (97%). Furthermore, healthy eating habits (high KIDMED index scores 92.4%), and low degree of depression score (95.5%) have been observed. We detected a statistically significant positive correlation between HbA1c and CDI scores (r: 0.27; p: 0.02), and a negative correlation between HbA1c and MMAS-6 motivation score (r: -0.30; p: 0.01). Conclusions. In this study, the effect of motivation and mood changes on glycemic control was more clearly demonstrated.

Context. Clinical research suggests that vitamin D deficiency correlates with mental illnesses. Objective. The aim was to prove that the patients from the psychiatric health care service in Serbia had higher vitamin D deficiency than patients from general practice. Design. The study had a cross-sectional design. Methods. The study included 47 patients aged 19 – 76 of both sexes with different mental disorders. We performed sample size calculation on available data for vitamin D deficiency in patients in health care facilities compared with the general population. The concentrations of vitamin D in serums were measured by HPLC (high performance/pressure liquid chromatography). Results. The mean value of vitamin D (standard deviation) in the whole group of study subjects was 16.27(10.62) ng/mL; 68.1% of the patients had a deficiency of vitamin D (25(OH)D<20 ng/mL). The difference is statistically significant from expected proportion of people with vitamin D deficiency in general practice (p=0.040). Serum concentrations of 25(OH)D were significantly correlated with serum concentrations of phosphorus (ϱ=0.336, p=0.024) and sodium (ϱ=0.304, p=0.038). Conclusions. The patients of psychiatry health care had significantly higher frequency of vitamin D deficiency than expected. There is a significant association between serum levels of vitamin D, and phosphate and sodium.

Aim. To evaluate the expression of Galectin-3, Fibronectin-1, Cytokeratin-19 and HBME1 in benign and malignant thyroid nodules and to assess their diagnostic value. Methods. Immunohistochemical analysis was performed on 59 surgically removed thyroid nodules, including 34 carcinomas (12 papillary, 2 tall cell variants, 3 lymph node metastases from papillary carcinoma, 5 follicular variants of papillary carcinoma (FVPTC), 3 anaplastic, 5 follicular and 4 Hürthle cell carcinomas), as well as 25 benign lesions (10 follicular adenomas, 4 Hürthle cell adenomas, 11 nodular goiters with surrounding normal thyroid tissue).3 expression in all malignant lesions except for one case of FVPTC and one follicular carcinoma. Normal thyrocytes and the majority of the benign lesions were negative for all markers. Statistical analysis of each protein confirmed that Galectin-3 was the most sensitive (94%), followed by Cytokeratin-19 (88%). Fibronectin-1 and HBME1 proved to be less sensitive (56% and 68%, respectively), but more specific (92% specificity for each of them). Coexpression of two or more proteins was restricted to carcinomas, while their concurrent absence was highly specific for benign lesions. Comparing the immunopositivity in follicular carcinoma versus adenoma we achieved 80% sensitivity for Galectin-3 and 100% specificity for HBME1. For distinguishing the Hürthle cell lesions, Fibronectin-1 turned out to be more sensitive than Galectin-3 and Cytokeratin- 19. Conclusion. Our findings suggest that immunohistochemical panel consisting of Galectin-3, Cytokeratin-19, HBME1 and Fibronectin-1 might contribute to differential diagnosis between malignant and benign thyroid nodules, including those with follicular architecture.

Objective. This study was to investigate RIP140 expression levels in the pancreas and islet β-cells in mice and rats and the role of RIP140 in cultured β-cells using the mouse pancreatic β-cell line MIN6. Methods. The MIN6 cell line stably overexpressing RIP140 was used. The effects of RIP140 on cell viability, cell cycle, apoptosis, insulin secretion, and its regulated genes were analyzed using flow cytometry, the MTT assay, Western blot analysis, reverse transcriptase (RT)-PCR, and enzyme-linked immunosorbent assay (ELISA). Results. Most of insulin-positive cells in islets expressed RIP140. In MIN6 cells, overexpression of RIP140 inhibited cell viability by reducing the number of cells in S phase and inhibiting proliferating cell nuclear antigen (PCNA) expression. We also found that overexpression of RIP140 inhibited Bcl-2 and mRNA expression of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and uncoupling protein 2 (UCP2) and increased levels of phosphorylated extracellular signalregulated protein kinases 1/2 (p-ERK1/2). However, apoptosis rate and levels of basal level of insulin secretion (BIS) and glucose-stimulated insulin (GSIS) were not significantly altered in MIN6 cells. Conclusions. RIP140 was expressed in the pancreas of mice and rats, particularly in β-cells, and participated in regulating β-cell function and proliferation.