ACTA ENDOCRINOLOGICA (BUC)

In response to increasing interest of the European Commission on large-scale\r\ngenotyping for complex diseases, including variability in ethnic minorities in\r\nEurope (HEALTH-2009-4.3.3-1), at the end of 2008 we composed the\r\nHAPLOGENDIS consortium with partners from Russia and European countries. A\r\nfirst program (SICA) was proposed in cooperation with Russian Federal Agency for\r\nScience and Innovation, focusing on comparative population genetics on diseases\r\naccompanied by insulin resistance. Beside the specificity in analyzing the human\r\ngenome with SNP (single nucleotide polymorphism) and defining haplotype\r\nstructure of genes, the program rises new hypotheses which directly link\r\ncolonization of Europe at the Neolithic period from Eastern Ukraine or Anatolia\r\nwith the development of agriculture and major dietary and life style changes that\r\nmay have an impact on the genome. Although there will be many occasions to\r\nreview both genetic and clinical detailed aspects, this short note will expose some\r\nunifying ideas that joint these partners.

Context. The expression of TSHR-C on the serum tetraiodothyronine (T4) and TSH receptor antibody (TRAb) levels are rarely studied. Objective. The effect of TSHR-c on T4 and TRAb levels and concomitant thyroid histological changes in mice was investigated. Design. Animal experimental study. Subjects and methods. Female BALB/c mice at 6-8 weeks of age were immunized with the thyroid stimulating hormone receptor antigen C-terminus (TSHR-C), and randomly divided into control group (treated with the corresponding concentrations of normal saline) and four experimental subgroups: TSHR-c1 subgroup (4 μg), TSHR-c2 subgroup (6 μg), TSHR-c3 subgroup (8 μg) and TSHR-c4 subgroup (10 μg). Serum T4 and TRAb levels were determined. Results. The serum T4 level decreased significantly in the experimental mice as the concentration increased. All the experimental mice were positive for serum TRAb (experimental groups: 40 positive/40, 100% vs. control group: 3 positive/10, 30%) compared to the control group (P =0.000). HE staining showed that the follicles in the control mice were composed of small to medium-sized round follicles, whereas the follicles in the experimental mice were irregularly enlarged under light microscope. Conclusions. TSHR-c immunization resulted in thyroid hormone changes like those observed in hypothyroidism, probably due to the induction of TRAb generation.

The aim of this study was to examine the highglucose and high fatty acid status effect on the development of atherosclerosis. Materials and Methods. We used rat thoracic aorta smooth muscle cell line A7r5. We investigated mechanisms underlying high-glucose and high fatty acid (oleic acid) conditions on vascular smooth muscle cell (VSMC) mimicking concurrent status of diabetes and dyslipidemia. Results. Glucose-oleic acid stimulated cell proliferation and migration while the proliferating cell nuclear antigen (PCNA) level and matrix metalloproteinase (MMP)-2 were activated. In addition, the expressions of connective tissue growth factor (CTGF) and fatty acid synthase (FASN) enhanced by glucose-oleic acid were increased. The proliferation signal mediated by glucoseoleic acid condition was demonstrated via CTGF/FASN, while MMP-2 was regulated by CTGF but not FASN. Conclusion. Oleic acid in the presence of high glucose level can induce VSMC proliferation and migration leading to diabetes-associated vascular atherosclerosis. Furthermore, via activation of CTGF, increased expression of FASN suggested a possibility of lipogenesis in VSMC which may also contribute to diabetes-associated vascular atherosclerosis.

Objective. To observe the effect of adiponectin on osteogenesis in type 2 diabetic rats. Methods. The 4th-week-old male SD rats were divided into normal control group (n=18) and diabetic model group (n = 42). Type 2 diabetes was induced by high-fat and high-sugar diet and intraperitoneal injection of a low dose of streptozotocin (STZ). The successfully-induced diabetic rats were divided into diabetic group (DM=18) and adiponectin intervention group (APN=18). APN group was injected with APN 10 μg/kg*d. The rats were separately sacrificed at the 4th, 8th and 12th week after the intervention. Bone microstructure and adipose tissue were observed via HE staining. Bone marrow was extracted from one side of the femur, and the supernatant was achieved by centrifugation. After BMD assessed by DXA, the other side of the femur was for further HE staining. Runx-2 expression in the bone marrow cells was detected by RT-PCR. BALP and AOPPs in bone marrow supernatant were assayed by ELISA. AGEs were detected by immunohistochemical staining. Results. With the feeding time over, blood glucose, AOPP, and AGEs were increased, and Runx-2 mRNA, BALP, BMD were decreased in diabetic rat group(P<0.05). Oxidative stress (OS) maker (AOPP) was decreased and osteogenesis makers (Runx2 mRNA, BALP) were increased after intervention with exogenous adiponectin (P<0.05). At the 8th and 12th week, the trabecular bone became thinner and broken, and the fat cell number increased in all 3 groups, especially in the DM group. The adiponectin intervention group showed that the trabecular bone structure was moderately restored. Conclusions. OS is obvious in bone microenvironment in diabetic rats. OS may have an inhibitory effect on regulation of osteogenic differentiation factor Runx2, causing down regulation of osteoblast differentiation and bone formation. Adiponectin may improve OS response and protect the bone structure.

Background. Osteoporosis has a high incidence after menopause, and at the same time the relationship between menopausal oestrogen deprivation and proinflammatory status is considered to be involved in postmenopausal bone turnover. Objective. The aim of this study was to evaluate the serum levels of IL-1β and of the TNFα in pre and postmenopausal women, as well as to investigate the relationship between these cytokines and bone mineral density. Design. A case-control study was performed during a period of 12 months. Subjects and Methods. The study included 150 women divided into 4 study groups. Serum levels of IL-1β and TNFα were determined using multiplex cytokine kits. BMD was measured by DXA at the level of the hip and lumbar spine. Results. Serum concentration of IL-1β is significantly higher in natural and surgically induced menopausal women, compared to women in the control group. Serum levels of TNFα in postmenopausal women and with surgically induced menopause are significantly higher than in fertile and premenopausal women. Serum levels of IL-1β are significantly higher in patients with osteopenia and osteoporosis compared to patients with normal BMD values. We found a negative correlation between serum levels of IL-1β, TNFα and BMD in pre and postmenopausal women, and in women with surgically induced menopause. Conclusions. Serum levels of IL- 1β and TNFα are significantly higher in menopausal women compared to fertile women. IL-1β is significantly higher in patients with osteopenia and osteoporosis than in women with normal BMD values, and IL-1β and TNFα associate negatively with BMD in pre and postmenopausal women, as well as in women with surgically induced menopause.

Context. Incidentally discovered solid adrenal tumors must be evaluated from two points of view: the risk of malignancy and the secretory feature. Objective. Our aim was to evaluate the surgical technique option in relation with clinical and histopathologic features. Design. We performed a retrospective study that included patients with adrenal gland tumors. Subjects and methods. All patients were operated between 2012 and 2019 by the same surgical team in a single center. Results. The batch included 102 patients with adrenal tumors operated through open surgery (OS, n=41) and laparoscopic surgery (LS, n=61). Tumor localization was especially on the right adrenal gland (n=52, 50.98%). Primary origin of the adrenal gland tumors was in 82 cases (80.39%) and a metastatic origin in 16 cases. Average dimension for surgical resected tumors was 4.02 cm (0.9-12 cm) for the LS group as compared to 7.22 cm (1.3-19 cm) for OS group with a predominant type of surgery represented by adrenalectomy and a conversion rate of 2.94%. The hospital stay was 7.22 days (5-12 days) in the LS group versus 12.72 days (6-57 days) in OS group with significant differences (p<0.01). Also, the postoperative recovery was significantly different (6.5 days versus 2.62 days, p<0.01). Conclusion. Laparoscopic approach represents the gold standard in adrenal gland tumors less than five centimeters in size. Adrenalectomy is mostly performed by LS and adenoma is the most frequent histopathologic type, while pheochromocytoma is operated through OS. LS has a significantly reduced hospitalization and postoperative stay compared to OS.

The objective of this study is to investigate the relationship between paraoxonase 1 (PON1) activity and dyslipidaemia in Northern Chinese diabetic patients with chronic renal failure (DM-CRF). For this purpose, 45 diabetic patients with CRF, 63 non-diabetic patients with CRF, 90 type 2 diabetic patients without CRF were investigated, as well as 70 subjects without diabetes and CRF. The serum PON1 activity and serum lipids, high-density lipoprotein cholesterol (HDLc) were determined. The results showed that, as compared to control subjects, serum ArE1/PON1 activities were significantly decreased in patients with diabetes, CRF and DM-CRF. In a further investigation of the relationship among ArE/PON1 and lipid parameters in all groups, not only serum ArE/PON1 activity, but also ratios of serum ArE/TC and ArE/HDL3c were found to be significantly decreased in the three groups, and the degree of decrement was DM-CRF>CRF>diabetes. In DM-CRF group, multiple regression analysis showed that ArE/PON1 was closely related to HDL2C, Apo A1 and HDLC. ArE/TC was also related to HDL2C, Apo A1, HDLC/TC and HDLC. In conclusion, serum ArE/PON1 can be one of the signals reflecting the disorder of lipid metabolism of CRF, especially in DM-CRF patients.

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Purpose. Short chain fatty acids (SCFAs) play a major regulatory role in adipocyte function and metabolism. The aim of this study was to investigate the effects of SCFAs on adiponectin and leptin expression in adipocytes, and also to determine whether the effects of SCFA treatment in visceral adipocytes obtained from healthy subjects are different relative to the effects in adipocytes from patients with type 2 diabetes. Materials and Methods. Human pericardiac preadipocytes and human pericardiac preadipocytes type 2 diabetes were differentiated into adipocytes for 21 days in 48-well plates. After differentiation, two kinds of mature adipocytes, human pericardiac adipocytes (HPAd) and human pericardiac adipocytes-type 2 diabetes (HPAd-T2D) were incubated with or without 1 mM of acetic acid (AA), butyrate acid (BA), and propionic acid (PA). After 48 hours of incubation, intracellular lipid accumulation was measured using oil red staining. In addition, mRNA levels of adiponectin, leptin and Peroxisome Proliferator-Activated Receptor γ (PPARγ) were determined by Real-Time PCR system. Results. In HPAd, SCFA supplementation did not inhibit lipid accumulation. By contrast, both AA (p<0.01) and PA (p<0.01) significantly inhibited lipid accumulation in HPAd-T2D. Regarding mRNA levels of adiponectin, no significant changes were found in HPAd, while all three types of SCFAs significantly increased (p<0.05) adiponectin expression in HPAd-T2D. Leptin mRNA expression levels were significantly increased by treatment with all three types of SCFAs in both HPAd (p<0.05) and HPAd-T2D (p<0.05). Conclusion. SCFAs inhibited lipid droplet accumulation and increased mRNA expression of adiponectin and leptin in T2D-derived adipocytes.

Despite several attempts to establish the role of QUS in clinical practice, issues such as definition of osteoporosis based on QUS, screening strategy and therapy efficacy for patients identified by QUS as having high risk of fracture remain a matter of debate. The present study aimed to evaluate the diagnostic agreement between two QUS techniques (heel QUS and proximal phalanges QUS) and DXA in an unselected population of Romanian women aged 24- 80 years, as well as to offer cut-off levels for QUS to distinct between women with or without osteoporosis identified by DXA. In women measured by both DXA and calcaneus QUS (c- QUS), bone mineral density (BMD) moderately correlated with stiffness index (SI) (L1-L4: r=+0.51, p<0.001; femoral neck: r=+0.53, p<0.001; hip: r=+0.57, p<0.001), while in women examined by both DXA and phalanx QUS (ph-QUS), BMD was positively related to amplitude-dependent speed of sound (Ad-SoS) (L1-L4: r=+0.47, p<0.001; femoral neck: r=+0.50, p<0.001; hip: r=+0.38, p<0.001) and ultrasound bone profile index (UBPI) (L1-L4: r=+0.44, p<0.001; femoral neck: r=+0.50, p<0.001; hip: r=+0.38, p<0.001). At a T-score cutoff level of -2.5SD, the high specificity but low sensitivity suggests a low false positive rate of c-QUS as a diagnostic test; still, several patients with the disease may not be correctly diagnosed. At the same cut-off level, ph-QUS showed higher sensitivity and lower specificity. Diagnostic agreement between DXA and QUS was poor, with k-scores ranging from 0.33 to 0.39 for c-QUS and from 0.14 to 0.29 for ph-QUS, respectively. Lowering c-QUS T-score cutoff for lumbar spine osteoporosis screening to -1.5SD and ph-QUS T-score cut-off to -1.9SD, respectively, improved sensitivity and had a minor effect on diagnostic agreement. Regardless of the evaluated site, neither c-QUS nor ph-QUS does represent an adequate predictor of BMD in Romanian women. Changing the diagnostic T-score threshold from -2.5 SD to -1.5 SD and -1.9 SD in subjects examined by c-QUS or ph-QUS, respectively, is followed by improved sensitivity and diagnostic agreement in the identification of patients with vertebral osteoporosis. Cut-off values may allow QUS to be used as a screening tool for spine and femur osteoporosis.