International Journal of Endocrinology The latest articles from Hindawi Publishing Corporation © 2016 , Hindawi Publishing Corporation . All rights reserved. Circulating CTRP1 Levels in Type 2 Diabetes and Their Association with FGF21 Mon, 23 May 2016 09:28:52 +0000 The goal of this study was to investigate whether circulating C1q/TNF-α-related protein 1 (CTRP1) levels are associated with diabetes. In addition, relationships between CTRP1 and other diabetes-related cytokines were elucidated, including adiponectin and fibroblast growth factor 21 (FGF21). A total of 178 subjects (78 men and 100 women) aged 29–70 years (mean age, 46.1 years) were randomly selected. The sera from a normal glucose tolerance group () and a prediabetes/type 2 diabetes group () were collected; then, circulating levels of CTRP1, adiponectin, and FGF21 were determined via enzyme-linked immunosorbent assay in all sera. Subjects with either prediabetes or diabetes exhibited higher circulating CTRP1 levels than healthy subjects. Sera analysis revealed that CTRP1 was positively correlated with age, body mass index, fasting blood glucose, and circulating FGF21 levels. However, CTRP1 was negatively correlated with total cholesterol and total circulating adiponectin levels in univariate analysis. In addition, multivariate analysis found that CTRP1 was independently associated with age, fasting blood glucose, and circulating FGF21 levels. CTRP1 was correlated with homeostasis model assessment-β (HOMA-β), but no correlation was observed with HOMA-insulin resistance. In conclusion, circulating CTRP1 levels are increased in subjects with type 2 diabetes and are positively associated with circulating FGF21 levels. Sora Han, Jong Dai Kim, Sunyi Lee, Ae Lee Jeong, Jeong Su Park, Hyo Jeong Yong, Ariundavaa Boldbaatar, Hye In Ka, Eun-Jung Rhee, Won-Young Lee, and Young Yang Copyright © 2016 Sora Han et al. All rights reserved. Evidences of Polymorphism Associated with Circadian System and Risk of Pathologies: A Review of the Literature Sun, 22 May 2016 11:07:53 +0000 The circadian system is a supraphysiological system that modulates different biological functions such as metabolism, sleep-wake, cellular proliferation, and body temperature. Different chronodisruptors have been identified, such as shift work, feeding time, long days, and stress. The environmental changes and our modern lifestyle can alter the circadian system and increase the risk of developing pathologies such as cancer, preeclampsia, diabetes, and mood disorder. This system is organized by transcriptional/tranductional feedback loops of clock genes Clock, Bmal1, Per1–3, and Cry1-2. How molecular components of the clock are able to influence the development of diseases and their risk relation with genetic components of polymorphism of clock genes is unknown. This research describes different genetic variations in the population and how these are associated with risk of cancer, metabolic diseases such as diabetes, obesity, and dyslipidemias, and also mood disorders such as depression, bipolar disease, excessive alcohol intake, and infertility. Finally, these findings will need to be implemented and evaluated at the level of genetic interaction and how the environment factors trigger the expression of these pathologies will be examined. F. J. Valenzuela, J. Vera, C. Venegas, S. Muñoz, S. Oyarce, K. Muñoz, and C. Lagunas Copyright © 2016 F. J. Valenzuela et al. All rights reserved. Thyroid Hormones, Autoantibodies, Ultrasonography, and Clinical Parameters for Predicting Thyroid Cancer Sun, 22 May 2016 10:02:58 +0000 Our objective was to evaluate thyroid nodule malignancy prediction using thyroid function tests, autoantibodies, ultrasonographic imaging, and clinical data. We conducted a retrospective cohort study in 1400 patients with nodular thyroid disease (NTD). The thyroid stimulating hormone (TSH) concentration was significantly higher in patients with differentiated thyroid cancer (DTC) versus benign thyroid nodular disease (BTND) (). The receiver operating characteristic curve of TSH showed an AUC of 0.58 (95% CI 0.53–0.62, ), sensitivity of 74%, and specificity of 57% at a cut-off of 1.59 mIU/L. There was an incremental increase in TSH concentration along with the increasing tumor size (). Thyroglobulin antibody (TgAb) concentration was associated with an increased risk of malignancy (), but this association was lost when the effect of TSH was taken into account (). Thyroid ultrasonographic characteristics, including fewer than three nodules, hypoechoic appearance, solid component, poorly defined margin, intranodular or peripheral-intranodular flow, and punctate calcification, can be used to predict the risk of thyroid cancer. In conclusion, our study suggests that preoperative serum TSH concentration, age, and ultrasonographic features can be used to predict the risk of malignancy in patients with NTD. Lin-zheng He, Tian-shu Zeng, Lin Pu, Shi-xiu Pan, Wen-fang Xia, and Lu-lu Chen Copyright © 2016 Lin-zheng He et al. All rights reserved. Regulation of Lipid Metabolism and Beyond Thu, 12 May 2016 17:24:57 +0000 Youngah Jo, Hiroaki Okazaki, Young-Ah Moon, and TongJin Zhao Copyright © 2016 Youngah Jo et al. All rights reserved. Interaction between Angiotensin II and Insulin/IGF-1 Exerted a Synergistic Stimulatory Effect on ERK1/2 Activation in Adrenocortical Carcinoma H295R Cells Thu, 12 May 2016 10:48:15 +0000 The cross talk between angiotensin II (Ang II) and insulin has been described mainly in cardiovascular cells, hepatocytes, adipocytes, and so forth, and to date no such cross talk was reported in adrenal. In this study, we examined the interaction between Ang II and insulin/IGF-1 in ERK and AKT signaling pathways and expression of steroidogenic enzymes in H295R cells. Compared to the control, 100 nM Ang II increased phospho-ERK1/2 approximately 3-fold. Insulin (100 nM) or IGF-1 (10 nM) alone raised phospho-ERK1/2 1.8- and 1.5-fold, respectively, while, after pretreatment with 100 nM Ang II for 30 min, insulin (100 nM) or IGF-1 (10 nM) elevated phospho-ERK1/2 level 8- and 7-fold, respectively. The synergistic effect of Ang II and insulin/IGF-1 on ERK1/2 activation was inhibited by selective AT1 receptor blocker, PKC inhibitor, and MEK1/2 inhibitor. Ang II marginally suppressed AKT activation under the basal condition, while it had no effect on phospho-AKT induced by insulin/IGF-1. Ang II significantly stimulated mRNA expression of CYP11B1 and CYP11B2, and such stimulatory effects were enhanced when cells were cotreated with insulin/IGF-1. We are led to conclude that Ang II in combination with insulin/IGF-1 had an evident synergistic stimulatory effect on ERK1/2 activation in H295R cells and the effect may be responsible for the enhanced steroid hormone production induced by Ang II plus insulin/IGF-1. An-li Tong, Fen Wang, Yun-ying Cui, Chun-yan Li, and Yu-xiu Li Copyright © 2016 An-li Tong et al. All rights reserved. The Effect of Levothyroxine Discontinuation Timing on Postoperative Hypothyroidism after Hemithyroidectomy for Papillary Thyroid Microcarcinoma Wed, 11 May 2016 11:31:08 +0000 Objective. No previous studies regarding the appropriate timing of thyroid hormone discontinuation after hemithyroidectomy have been published. This study aimed to identify the appropriate timing for levothyroxine discontinuation after hemithyroidectomy among patients with papillary thyroid microcarcinoma (PTMC). Methods. This study retrospectively evaluated 304 patients who underwent ≥1 attempt to discontinue levothyroxine after hemithyroidectomy for treating PTMC between January 2008 and December 2013. Fifty-three patients were excluded because of preoperative hypothyroidism or hyperthyroidism, a history of thyroid hormone or antithyroid therapy, no available serological data, or a postoperative follow-up of <24 months. We evaluated the associations of successful levothyroxine discontinuation with patient age, sex, preoperative serological data, underlying thyroid gland histopathology, anteroposterior diameter of the residual thyroid gland, number of discontinuation attempts, and initial discontinuation timing. Results. Among the 251 included patients, 125 patients (49.8%) achieved successful levothyroxine discontinuation during the follow-up period after hemithyroidectomy. There was a significant difference in the outcomes for patients who underwent an initial discontinuation attempt at ≤3 months and ≥4 months after hemithyroidectomy (p < 0.001). There were significant differences in the discontinuation outcomes according to underlying thyroid histopathology (p = 0.001), preoperative thyroid-stimulating hormone levels (p < 0.001), and number of discontinuation attempts (p < 0.001). Conclusions. Among patients with PTMC, the initial levothyroxine discontinuation attempt is recommended at ≥4 months after hemithyroidectomy. Tae Kwun Ha, Dong Wook Kim, Ha Kyoung Park, Jin Wook Baek, Yoo Jin Lee, Young Mi Park, Do Hun Kim, Soo Jin Jung, and Ki Jung Ahn Copyright © 2016 Tae Kwun Ha et al. All rights reserved. Human Papilloma Virus Infection in Patients with Male Accessory Gland Infection: Usefulness of the Ultrasound Evaluation Tue, 03 May 2016 15:21:15 +0000 This study evaluated the ultrasound (US) features of 20 patients with MAGI and concomitant papilloma virus (HPV) infection compared to 20 patients with microbial (presence of Chlamydia trachomatis alone) MAGI and 20 patients with amicrobial (inflammatory) MAGI. Patients with HPV infection showed significantly () higher total prostate, seminal vesicles, and epididymal US signs (18.0 ± 2.0) compared to the other 2 groups (12.0 ± 4.0 versus 10.0 ± 3.0, resp.). In addition, patients with MAGI and HPV had a higher prevalence of complicated forms of MAGI [prostatovesiculitis (PV) and prostate-vesiculo-epididymitis (PVE)] and a higher frequency of the fibrosclerotic variant compared to the other groups (70.0 ± 10.0% versus 48.0 ± 5.0% versus 15.0 ± 10.0%). Moreover, HPV infected patients had a higher number of US criteria suggestive for MAGI in the periurethral region of the prostate compared to the other groups. In particular, the patients showed a higher ratio between periurethral and lobar US criteria distribution (5.0 versus 0.5). Finally, the seminal fluid concentration of leukocytes (2.0 ± 0.2 versus 1.3 ± 0.3 versus 1.0 ± 0.3 mil/mL) was significantly higher and sperm progressive motility was significantly lower in these patients compared to other groups. Rosita A. Condorelli, Enzo Vicari, Laura M. Mongioi, Giorgio I. Russo, Giuseppe Morgia, Sandro La Vignera, and Aldo E. Calogero Copyright © 2016 Rosita A. Condorelli et al. All rights reserved. Lipid Profile in Adolescent Girls with Type 1 Diabetes Mellitus and Hyperandrogenemia Wed, 27 Apr 2016 13:08:48 +0000 Study Objectives. The study aim was to evaluate whether hyperandrogenemia in adolescent girls with type 1 diabetes mellitus (T1DM) may adversely influence lipid profile. Design and Participants. Lipid levels in 16 diabetic girls with biochemical hyperandrogenemia (T1DM-H) aged 16.3 ± 1.2 years were compared to 38 diabetic girls with normal androgen levels (T1DM-N) aged 15.8 ± 1.2 years. 15 healthy girls served as controls (CG). In all patients, anthropometric measurements were done, and androgens and SHBG were assessed. Results. In T1DM-H, total cholesterol (TC) and low density cholesterol (LDL-ch) were significantly higher than in CG (196.1 ± 41.2 versus 162.7 ± 31.7 mg/dL, ; 117.3 ± 33.1 versus 91.3 ± 27.8 mg/dL, , resp.). Their LDL-ch, non-high density cholesterol (non-HDL-ch) concentrations, and LDL/HDL ratio were also significantly higher than in T1DM-N (117.3 ± 33.1 versus 97.7 ± 26.7 mg/dL, ; 137.3 ± 42.9 versus 113.3 ± 40.4 mg/dL, ; 2.8 ± 3.7 versus 1.6 ± 0.5, , resp.). In stepwise multiple linear regression, free androgen index (FAI) and waist-to-hip ratio (WHR) were associated with TC (, ), non-HDL-ch (, ), and LDL-ch (, ). Triglycerides and LDL/HDL ratio were (, , , resp.) related to testosterone, FAI, WHR, and mean HbA1c. Conclusion. Lipid profile in diabetic adolescent girls is adversely influenced by the androgens level, particularly in the group with higher WHR and poorer glycemic control. Agnieszka Zachurzok, Grazyna Deja, Aneta Gawlik, Agnieszka Drosdzol-Cop, Katarzyna Klimek, and Ewa Malecka-Tendera Copyright © 2016 Agnieszka Zachurzok et al. All rights reserved. Adipokines and Insulin Resistance in Young Adult Survivors of Childhood Cancer Sun, 24 Apr 2016 15:35:50 +0000 We examined the association between adipokines (leptin, adiponectin, and resistin), radiotherapy, measurement of body fat, and insulin resistance among young adult survivors of childhood cancer (CCS). Materials and Methods. Seventy-six survivors were included (mean age years). Insulin resistance (IR) was calculated using the homeostasis model assessment (HOMA-IR). The serum levels of adipokines were assayed by immunoassays. Fat mass was evaluated by DXA. Results. Mean adiponectin level and mean body FAT were higher in the examined females than in males ( ng/mL versus  ng/mL, ; % versus %, ). Among CCS, one of 75 patients met the criteria of insulin resistance, and in 14 patients there was impaired fasting glucose. The multiple regression model for females showed that leptin/adiponectin ratio (LA ratio) significantly affected HOMA-IR (increase of 0.024 per each unit of LA ratio; ). Radiotherapy had no effect on serum adipokines and IR. Conclusion. The observed results support the hypothesis that adiponectin might be associated with insulin resistance and it can not be ruled out that changes in the mean level of adiponectin per FAT mass or leptin/adiponectin ratio may precede the occurrence of insulin resistance in the future. Eryk Latoch, Katarzyna Muszynska-Roslan, Agata Panas, Anna Panasiuk, Malgorzata Sawicka-Zukowska, Beata Zelazowska-Rutkowska, Ewa Zabrocka, and Maryna Krawczuk-Rybak Copyright © 2016 Eryk Latoch et al. All rights reserved. The Protective Effect of Beraprost Sodium on Diabetic Nephropathy by Inhibiting Inflammation and p38 MAPK Signaling Pathway in High-Fat Diet/Streptozotocin-Induced Diabetic Rats Sun, 24 Apr 2016 13:53:21 +0000 Background. p38 mitogen-activated protein kinase (MAPK) plays a crucial role in regulating signaling pathways implicated in inflammatory processes leading to diabetic nephropathy (DN). This study aimed to examine p38 MAPK activation in DN and determine whether beraprost sodium (BPS) ameliorates DN by inhibiting inflammation and p38 MAPK signaling pathway in diabetic rats. Methods. Forty male Sprague Dawley (SD) rats were randomly divided into the normal control group, type 2 diabetic group, and BPS treatment group. At the end of the 8-week experiment, we measured renal pathological changes and the activation of the p38 MAPK signaling pathway and inflammation. Result. After BPS treatment, renal function, 24-hour urine protein, lipid profiles, and blood glucose level were improved significantly; meanwhile, inflammation and the expression of p38 MAPK signaling pathway in the diabetic kidney were attenuated. Conclusions. BPS significantly prevented type 2 diabetes induced kidney injury characterized by renal dysfunction and pathological changes. The protective mechanisms are complicated but may be mainly attributed to the inhibition of the p38 MAPK signaling pathway and inflammation in the diabetic kidney. Li Peng, Jie Li, Yixing Xu, Yangtian Wang, Hong Du, Jiaqing Shao, and Zhimin Liu Copyright © 2016 Li Peng et al. All rights reserved. 11β-Hydroxysteroid Dehydrogenase 2 in Preeclampsia Thu, 21 Apr 2016 12:38:05 +0000 Preeclampsia is a serious medical problem affecting the mother and her child and influences their health not only during the pregnancy, but also many years after. Although preeclampsia is a subject of many research projects, the etiology of the condition remains unclear. One of the hypotheses related to the etiology of preeclampsia is the deficiency in placental 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2), the enzyme which in normal pregnancy protects the fetus from the excess of maternal cortisol. The reduced activity of the enzyme was observed in placentas from pregnancies complicated with preeclampsia. That suggests the overexposure of the developing child to maternal cortisol, which in high levels exerts proapoptotic effects and reduces fetal growth. The fetal growth restriction due to the diminished placental 11β-HSD2 function may be supported by the fact that preeclampsia is often accompanied with fetal hypotrophy. The causes of the reduced function of 11β-HSD2 in placental tissue are still discussed. This paper summarizes the phenomena that may affect the activity of the enzyme at various steps on the way from the gene to the protein. Katarzyna Kosicka, Anna Siemiątkowska, and Franciszek K. Główka Copyright © 2016 Katarzyna Kosicka et al. All rights reserved. FGF21 Is Associated with Acanthosis Nigricans in Obese Patients Wed, 13 Apr 2016 13:54:46 +0000 Objective. We aimed to investigate the relationship between FGF21 and obesity-related acanthosis nigricans (AN). Methods. 40 obese patients without AN (OB group), 40 obese patients with AN (AN group), and 40 healthy volunteers (control group, CON) were included in this study. Weight, BMI, lipid profile, FFA, UA, and CRP were measured in all participants. Oral glucose tolerance tests (OGTT) were performed and serum glucose and plasma insulin were measured. Serum FGF21 was measured by ELISA. Results. Compared with OB group, AN group had higher levels of fasting insulin and homeostasis model of assessment for insulin resistance (HOMA-IR) (), but lower serum levels of blood glucose. The difference of FGF21 among three groups was significant and AN group showed the highest serum level of FGF21 (). Serum FGF21 was most positively correlated with fasting insulin and HOMA-IR. Multiple logistic analysis showed that FGF21 was the independent risk factor for AN (OR 4.550; 95% CI 1.054–19.635; ). Conclusion. AN patients had more serious hyperinsulinemia but better serum levels of blood glucose than OB. Increased FGF21 is associated with AN in obese patients and may be considered as compensatory response to the decreased insulin sensitivity. Yueye Huang, Jie Yang, Yan Li, Jiaqi Chen, Kexiu Song, Xingchun Wang, Le Bu, Xiaoyun Cheng, Jiying Wang, and Shen Qu Copyright © 2016 Yueye Huang et al. All rights reserved. Growth Hormone Therapy Benefits Pituitary Stalk Interruption Syndrome Patients with Short Stature: A Retrospective Study of 75 Han Chinese Wed, 13 Apr 2016 12:04:05 +0000 Objective. We aim to investigate the long-term benefits of growth hormone (GH) therapy in short stature adolescents and adults with pituitary stalk interruption syndrome (PSIS), which would be beneficial for future clinical applications. Design and Methods. In this study, initial height, final height, total height gain, and GH treatment history were retrospectively investigated in 75 Chinese PSIS patients. We compared height gain between the GH treated cohort and untreated cohort and explored the impact of different GH therapy duration on height gain. Results. For GH treated patients, their final height (SDS) increased from (−6.93~2.80) at bone age (BA) of 11.2 (5.0~17.0) years to (−7.82~1.05) at BA of 16.6 (8.0~18.0) years (). And GH treated patients had more height gain than the untreated patients (). There was a significant difference between the different GH therapy duration groups (): GH 0 versus GH 3, ; GH 1 versus GH 3, ; GH 2 versus GH 3, . Conclusion. Adult Chinese PSIS patients with short stature benefited the most from at least 12 months of GH therapy. Although patient diagnosis age was lagged behind in the developing countries, GH treatment was still effective for them and resulted in a higher final height and more height gain. Cheng-Zhi Wang, Ling-Ling Guo, Bai-Yu Han, An-Ping Wang, Hong-Yan Liu, Xing Su, Qing-Hua Guo, and Yi-Ming Mu Copyright © 2016 Cheng-Zhi Wang et al. All rights reserved. Ghrelin Protects against Dexamethasone-Induced INS-1 Cell Apoptosis via ERK and p38MAPK Signaling Tue, 12 Apr 2016 11:52:05 +0000 Glucocorticoid excess induces apoptosis of islet cells, which may result in diabetes. In this study, we investigated the protective effect of ghrelin on dexamethasone-induced INS-1 cell apoptosis. Our data showed that ghrelin (0.1 μM) inhibited dexamethasone-induced (0.1 μM) apoptosis of INS-1 cells and facilitated cell proliferation. Moreover, ghrelin upregulated Bcl-2 expression, downregulated Bax expression, and decreased caspase-3 activity. The protective effect of ghrelin against dexamethasone-induced INS-1 cell apoptosis was mediated via growth hormone secretagogue receptor 1a. Further studies revealed that ghrelin increased ERK activation and decreased p38MAPK expression after dexamethasone treatment. Ghrelin-mediated protection of dexamethasone-induced apoptosis of INS-1 cells was attenuated using the ERK inhibitor U0126 (10 μM), and cell viability increased using the p38MAPK inhibitor SB203580 (10 μM). In conclusion, ghrelin could protect against dexamethasone-induced INS-1 cell apoptosis, at least partially via GHS-R1a and the signaling pathway of ERK and p38MAPK. Chengshuo Zhang, Le Li, Bochao Zhao, Ao Jiao, Xin Li, Ning Sun, and Jialin Zhang Copyright © 2016 Chengshuo Zhang et al. All rights reserved. Tetrahydro-iso-alpha Acids Antagonize Estrogen Receptor Alpha Activity in MCF-7 Breast Cancer Cells Tue, 12 Apr 2016 11:25:47 +0000 Tetrahydro-iso-alpha acids commonly called THIAA or Tetra are modified hop acids extracted from hop (Humulus lupulus L.) which are frequently used in brewing industry mainly in order to provide beer bitterness and foam stability. Interestingly, molecular structure of tetrahydro-iso-alpha acids is close to a new type of estrogen receptor alpha (ERα) antagonists aimed at disrupting the binding of coactivators containing an LxxLL motif (NR-box). In this work we show that THIAA decreases estradiol-stimulated proliferation of MCF-7 (ERα-positive breast cancer cells). Besides, we show that it inhibits ERα transcriptional activity. Interestingly, this extract fails to compete with estradiol for ERα binding and does not significantly impact the receptor turnover rate in MCF-7 cells, suggesting that it does not act like classical antiestrogens. Hence, we demonstrate that THIAA is able to antagonize ERα estradiol-induced recruitment of the LxxLL binding motif. Maëlle Lempereur, Claire Majewska, Amandine Brunquers, Sumalee Wongpramud, Bénédicte Valet, Philippe Janssens, Monique Dillemans, Laurence Van Nedervelde, and Dominique Gallo Copyright © 2016 Maëlle Lempereur et al. All rights reserved. Maternal and Fetal Lipid and Adipokine Profiles and Their Association with Obesity Tue, 12 Apr 2016 11:16:44 +0000 Background. Maternal metabolic changes impact fetal metabolism resulting in a higher risk for developing chronic diseases later in life. The aim of this study was to assess the association between maternal and fetal adipokine and lipid profiles, as well as the influence of maternal weight on this association. Methods. Healthy pregnant women at term who delivered by C-section were enrolled. Maternal and fetal glucose, lipid profile, adiponectin, leptin, and resistin levels were analyzed by obesity and maternal weight gain. Statistics included descriptives, correlations, and mean differences (SPSS v20.0). Results. Adiponectin and resistin concentrations were higher in fetal blood, while leptin was lower (). A significant inverse association between maternal resistin and fetal LDL-cholesterol (LDL-C) (; ) was observed. A positive correlation was found between maternal and fetal resistin (; ). Women with excessive weight gain had higher leptin levels and their fetuses showed higher LDL-C levels (). Conclusions. Maternal resistin showed an inverse association with fetal LDL-C, suggesting that maternal adiposity status may play an active role in the regulation of fetal lipid profile and consequently, in fetal programming. Excessive maternal weight gain during pregnancy may exert an effect over metabolic mediators in both mother and newborn. Mario Solis-Paredes, Salvador Espino y Sosa, Guadalupe Estrada-Gutierrez, Sonia Nava-Salazar, Veronica Ortega-Castillo, Mario Rodriguez-Bosch, Eyerahi Bravo-Flores, Aurora Espejel-Nuñez, Maricruz Tolentino-Dolores, Rubí Gaona-Estudillo, Nancy Martinez-Bautista, and Otilia Perichart-Perera Copyright © 2016 Mario Solis-Paredes et al. All rights reserved. Histopathologic Evaluation of Nonalcoholic Fatty Liver Disease in Hypothyroidism-Induced Rats Thu, 07 Apr 2016 14:05:29 +0000 It is speculated that thyroid hormones may be involved in nonalcoholic fatty liver disease (NAFLD) pathogenesis. A literature scan, however, demonstrated conflicting results from studies investigating the relationship between hypothyroidism and NAFLD. Therefore, our study aims to evaluate NAFLD, from the histopathologic perspective, in hypothyroidism-induced rats. Wistar rats were divided into 2 groups: the experimental group consumed water containing methimazole 0.025% (MMI, Sigma, USA) for 12 weeks and the control group consumed tap water. At the end of week 12, serum glucose, ALT, AST, triglyceride, HDL, LDL, TSH, fT4, fT3, visfatin, and insulin assays were performed. Sections were stained with hematoxylin-eosin and “Oil Red-O” for histopathologic examination of the livers. In our study, we detected mild hepatosteatosis in all hypothyroidism-induced rats. There was statistically significant difference with respect to obesity between the two groups (). The mean fasting blood glucose was 126.25 ± 23.4 mg/dL in hypothyroidism-induced group and 102.63 ± 15.51 mg/dL in the control group, with a statistically significant difference between the groups (). The two groups did not differ statistically significantly with respect to visfatin levels (). In conclusion, we found that hypothyroidism-induced rats had mild hepatosteatosis as opposed to the control group histopathologically. Our study indicates that hypothyroidism can cause NAFLD. Şule Demir, Mustafa Ünübol, Serap Ünübol Aypak, Emrah İpek, Serdar Aktaş, Gamze Sevri Ekren, Murat Yılmaz, Recai Tunca, and Engin Güney Copyright © 2016 Şule Demir et al. All rights reserved. Investigation of Vitamin D-Binding Protein Polymorphism Impact on Coronary Artery Disease and Relationship with Longevity: Own Data and a Review Wed, 06 Apr 2016 09:38:50 +0000 The aim of the study was to assess the effect of vitamin D-binding protein (DBP) polymorphism on coronary artery disease (CAD). DBP phenotypes were identified in the groups: control (), men suffering from CAD (), and long-lived individuals (). Isoelectric focusing of DBP phenotypes in serum was performed on polyacrylamide gel. Distribution of DBP phenotypes in the study groups was found to be in Hardy-Weinberg equilibrium. Gc1s-1s phenotype and Gc1s allele frequency in CAD groups were significantly higher than in control, and Gc1s allele frequency was found significantly more often in CAD compared with long-lived group (). The Gc2 allele frequency in control was higher as compared with Gc2 frequency in CAD group (). The Gc2-2 phenotype was more frequent in long-lived survivors than in the CAD group (). It was found that the Gc1s allele significantly increased the risk of CAD with the odds ratio (OR) equal to 1.45 () and showed Gc2 to be related with a decreased risk of CAD (OR = 0.69; ). Authors review the role of DBP in resistance to atherosclerosis and cancer as the main longevity determinants. Donatas Stakisaitis, Vita Lesauskaitė, Milda Girdauskaitė, Ernestas Janulionis, Albertas Ulys, and Rimantas Benetis Copyright © 2016 Donatas Stakisaitis et al. All rights reserved. Extending the Impact of RAC1b Overexpression to Follicular Thyroid Carcinomas Tue, 05 Apr 2016 14:13:41 +0000 RAC1b is a hyperactive variant of the small GTPase RAC1 known to be a relevant molecular player in different cancers. Previous studies from our group lead to the evidence that its overexpression in papillary thyroid carcinoma (PTC) is associated with an unfavorable prognosis. In the present study, we intended to extend the analysis of RAC1b expression to thyroid follicular neoplasms and to seek for clinical correlations. RAC1b expression levels were determined by RT-qPCR in thyroid follicular tumor samples comprising 23 follicular thyroid carcinomas (FTCs) and 33 follicular thyroid adenomas (FTAs). RAC1b was found to be overexpressed in 33% of carcinomas while no RAC1b overexpression was documented among follicular adenomas. Patients with a diagnosis of FTC were divided into two groups based on longitudinal evolution and final outcome. RAC1b overexpression was significantly associated with both the presence of distant metastases ( = 0.01) and poorer clinical outcome ( = 0.01) suggesting that, similarly to that previously found in PTCs, RAC1b overexpression in FTCs is also associated with worse outcomes. Furthermore, the absence of RAC1b overexpression in follicular adenomas hints its potential as a molecular marker likely to contribute, in conjunction with other putative markers, to the preoperative differential diagnosis of thyroid follicular lesions. Márcia Faria, Liliana Capinha, Joana Simões-Pereira, Maria João Bugalho, and Ana Luísa Silva Copyright © 2016 Márcia Faria et al. All rights reserved. A Study on Central Lymph Node Metastasis in 543 cN0 Papillary Thyroid Carcinoma Patients Sun, 03 Apr 2016 13:38:29 +0000 Background. Papillary thyroid carcinoma (PTC) with central lymph node metastases (CLNMs) is common. The objective of this study was to investigate the incidence and risk factors of lymph node metastasis patients with PTC. Patients and Methods. Between January 2013 and February 2015, a retrospective study of 543 patients with PTC undergoing hemithyroidectomy or total thyroidectomy with routine central lymph node dissection (CLND) was analyzed. Clinicopathologic risk factors for CLNM were studied using univariate and multivariate analysis by SPSS 22.0 software. Results. The incidence of CLNMs in PTC patients was 38.1% (207/543). In the multivariate analysis, male gender (, OR: 1.984), age <45 years (, OR: 1.934), bilaterality (, OR: 1.585), tumor size ≥0.25 cm (, OR: 7.655), and external extension (, OR: 7.579) were independent risk factors of CLNMs. Furthermore, in PTC patients with tumor size <0.25 cm, all 7 males and 21 patients with unilaterality were not found to have CLNMs. Conclusions. CLNMs are prevalent in the PTC patients with the following risk factors: male gender, age <45 years, bilaterality, tumor size ≥0.25 cm, and external extension. PTC patients with tumor size <0.25 cm, male patients, and patients with unilateral lesion could be considered safe from CLNMs. Huanhuan Yan, Xiaoqian Zhou, Hui Jin, Xiang Li, Miao Zheng, Xu Ming, Ruitao Wang, and Jun Liu Copyright © 2016 Huanhuan Yan et al. All rights reserved. Maternal High-Fat Diet during Pregnancy and Lactation Influences Obestatin and Ghrelin Concentrations in Milk and Plasma of Wistar Rat Dams and Their Offspring Thu, 31 Mar 2016 06:23:19 +0000 The study aims to establish the effect of a maternal high-fat diet on obestatin concentration, total ghrelin, and ghrelin/obestatin ratio during pregnancy and lactation of Wistar rats and their offspring in the first 21 days of life. On the mating day, females were randomly allocated and fed either a high-fat diet (30% of fat; HF) or breeding diet (5% fat; BD) till the 21st day of lactation. Hormones were analyzed in the blood plasma and milk of rat dams as well as in the blood plasma of their offspring. HF resulted in a significant decrease in obestatin level on the 14th day of lactation and elevation on the 21st day. Plasma obestatin in HFD offspring was significantly higher than in BD ones. HF diet did not significantly affect dam plasma ghrelin until the 21st day of lactation. The ghrelin concentrations in milk after both diets were significantly lower than in blood plasma. Milk ghrelin in HF dams was significantly higher than in the BD ones. Plasma ghrelin from HF offspring was significantly higher than that from BD dams. Our results demonstrate that a maternal HF diet during pregnancy and lactation influences ghrelin and obestatin level in both dams and their offspring. Monika Słupecka, Katarzyna Romanowicz, and Jarosław Woliński Copyright © 2016 Monika Słupecka et al. All rights reserved. A Comparison of Tissue versus Swab Culturing of Infected Diabetic Foot Wounds Wed, 30 Mar 2016 16:21:36 +0000 Objective. To compare the efficacy of swabbing versus tissue biopsy for microbiological diagnosis of diabetic foot infection. Methods. This was a prospective trial. Fifty-six patients with diabetic foot infection were divided into the following 3 groups according to the PEDIS grading system: grade 2 (), grade 3 (), and grade 4 (). Two specimens were collected from each wound for microbial culturing after debridement, including a superficial swab and a deep tissue punch biopsy specimen. Results. Swab culturing identified all of the microorganisms isolated from the corresponding deep tissue specimens in 9/10 of grade 2 wounds (90.0%), and this proportion decreased to 12/29 (41.4%) and 7/17 (41.2%) for grades 3 and 4 wounds, respectively (). Moreover, the sensitivity for identifying Gram-negative bacteria, such as E. coli and Citrobacter, by swabbing was low (33.3%). In addition, some Gram-negative bacteria, such as Serratia and Ralstonia pickettii, were isolated from deep tissues but not from swabs. Conclusions. Swab culturing may be reliable for identification of pathogens in diabetic foot wounds classified as grade 2. However, it is advisable to culture deep tissue specimens for wounds of grade ≥3 because swab culturing is associated with a high risk of missing pathogens, especially Gram-negative bacteria. Ying Huang, Ying Cao, Mengchen Zou, Xiangrong Luo, Ya Jiang, Yaoming Xue, and Fang Gao Copyright © 2016 Ying Huang et al. All rights reserved. Therapeutic Outcome of Second Primary Malignancies in Patients with Well-Differentiated Thyroid Cancer Tue, 29 Mar 2016 13:52:02 +0000 Background. The aims of this study were to analyze the clinical characteristics of SPM in patients with well-differentiated thyroid cancer and to determine the long-term prognosis in patients with double malignancies. Materials and Methods. We retrospectively analyzed 2,864 patients with well-differentiated thyroid cancer and a mean age of years. Of these, 200 (7.0%) were diagnosed with SPM, 115 of which were diagnosed with metachronous SPM. Results. Of 2,864 patients, 163 (5.7%) patients died of thyroid cancer and 301 (10.5%) died of any cause by the end of the follow-up period. Multivariate analysis identified age, SPM, external radiotherapy, TNM stage, and postoperative serum Tg level to be factors independently associated with decreased survival. Of 200 patients with SPM, 74 (37.0%) died. In comparison to the anachronous and synchronous groups, the metachronous SPM group had a higher mean age; more advanced tumor, node, and metastasis stage; lower remission rate; higher postoperative radioactive iodide (131I) accumulated dose; a higher proportion of patients who underwent external radiotherapy; and higher thyroid cancer and total mortality rates. Conclusions. Patients with well-differentiated thyroid carcinoma and metachronous SPM had worse prognoses compared to patients without SPM. Miaw-Jene Liou, Ngan-Ming Tsang, Chuen Hsueh, Tzu-Chieh Chao, and Jen-Der Lin Copyright © 2016 Miaw-Jene Liou et al. All rights reserved. Pituitary Morphology and Function in 43 Children with Central Diabetes Insipidus Tue, 29 Mar 2016 07:38:20 +0000 Objective. In pediatric central diabetes insipidus (CDI), etiology diagnosis and pituitary function monitoring are usually delayed. This study aimed to illustrate the importance of regular follow-up and pituitary function monitoring in pediatric CDI. Methods. The clinical, hormonal, and neuroradiological characteristics of children with CDI at diagnosis and during 1.5–2-year follow-up were collected and analyzed. Results. The study included 43 CDI patients. The mean interval between initial manifestation and diagnosis was 22.29 ± 3.67 months (range: 2–108 months). The most common complaint was polyuria/polydipsia. Causes included Langerhans cell histiocytosis, germinoma, and craniopharyngioma in 2, 5, and 4 patients; the remaining were idiopathic. No significant changes were found during the 1.5–2 years after CDI diagnosis. Twenty-three of the 43 cases (53.5%) had ≥1 anterior pituitary hormone deficiency. Isolated growth hormone deficiency was the most frequent abnormality (37.5%) and was not associated with pituitary stalk diameter. Multiple pituitary hormone deficiencies were found in 8 cases with pituitary stalk diameter > 4.5 mm. Conclusion. Diagnosis of CDI is usually delayed. CDI with a pituitary stalk diameter > 4.5 mm carries a higher risk of multiple pituitary hormone deficiencies. Long-term MRI and pituitary function follow-ups are necessary for children with idiopathic CDI. Wendong Liu, Limin Wang, Minghua Liu, and Guimei Li Copyright © 2016 Wendong Liu et al. All rights reserved. Sexual Dimorphism in the Regulation of Estrogen, Progesterone, and Androgen Receptors by Sex Steroids in the Rat Airway Smooth Muscle Cells Thu, 24 Mar 2016 15:55:16 +0000 The role of sex hormones in lung is known. The three main sex steroid receptors, estrogen, progesterone, and androgen, have not been sufficiently studied in airway smooth muscle cells (ASMC), and the sex hormone regulation on these receptors is unknown. We examined the presence and regulation of sex hormone receptors in female and male rat ASMC by Western blotting and flow cytometry. Gonadectomized rats were treated with 17β-estradiol, progesterone, 17β-estradiol + progesterone, or testosterone. ASMC were enzymatically isolated from tracheas and bronchi. The experiments were performed with double staining flow cytometry (anti-α-actin smooth muscle and antibodies to each hormone receptor). ERα, ERβ, tPR, and AR were detected in females or males. ERα was upregulated by E2 and T and downregulated by P4 in females; in males, ERα was downregulated by P4, E + P, and T. ERβ was downregulated by each treatment in females, and only by E + P and T in males. tPR was downregulated by P4, E + P, and T in females. No hormonal regulation was observed in male receptors. AR was downregulated in males treated with E + P and T. We have shown the occurrence of sex hormone receptors in ASMC and their regulation by the sex hormones in female and male rats. Abraham Zarazúa, Aliesha González-Arenas, Gabriela Ramírez-Vélez, Blanca Bazán-Perkins, Christian Guerra-Araiza, and María G. Campos-Lara Copyright © 2016 Abraham Zarazúa et al. All rights reserved. Assessment of Bone Mineral Density in Male Patients with Chronic Obstructive Pulmonary Disease by DXA and Quantitative Computed Tomography Mon, 21 Mar 2016 12:52:42 +0000 The purpose of this study is to identify the prevalence of osteoporosis in male patients with chronic obstructive pulmonary disease (COPD) by dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT) and to compare the diagnostic abilities of the above methods. Thirty-seven male patients with established COPD were examined with DXA and standard QCT in lumbar spine, including L1, L2, and L3 vertebrae. -scores and bone mineral density values were calculated by DXA and QCT method, respectively. Comparative assessment of the findings was performed and statistical analysis was applied. QCT measurements found more COPD patients with impaired bone mineral density compared to DXA, namely, 13 (35.1%) versus 12 (32.4%) patients with osteopenia and 16 (43.2%) versus 9 (16.2%) patients with osteoporosis (). More vertebrae were found with osteoporosis by QCT compared to DXA (). The prevalence of osteoporosis among male patients with COPD is increased and DXA may underestimate this risk. QCT measurements have an improved discriminating ability to identify low BMD compared to DXA measurements because QCT is able to overcome diagnostic pitfalls including aortic calcifications and degenerative spinal osteophytes. George Fountoulis, Theodora Kerenidi, Constantinos Kokkinis, Panagiotis Georgoulias, Paschal Thriskos, Konstantinos Gourgoulianis, Ioannis Fezoulidis, Katerina Vassiou, and Marianna Vlychou Copyright © 2016 George Fountoulis et al. All rights reserved. Trimester- and Assay-Specific Thyroid Reference Intervals for Pregnant Women in China Mon, 21 Mar 2016 09:50:14 +0000 Objective. The guidelines of the American Thyroid Association (ATA) recommend an upper limit reference interval (RI) of thyroid stimulating hormone (TSH) of 2.5 mIU/L in the first trimester of pregnancy and 3.0 mIU/L in subsequent trimesters, but some reported ranges in China are significantly higher. Our study aimed to establish trimester- and assay-specific RIs for thyroid hormones in normal pregnant Chinese women. Methods. In this cross-sectional study, 2540 women with normal pregnancies (first trimester, ; second trimester, ; third trimester, ) and 237 healthy nonpregnant control subjects were recruited. Serum TSH, free thyroxin (FT4), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TgAb) levels were determined by automated chemiluminescence with an Immulite 2000 system (Siemens, Erlangen, Germany). After outliers were excluded, the 2.5–97.5th percentiles were used to define the RIs. Results. The RIs of thyroid function in the first, second, and third trimesters of pregnancy and in nonpregnant controls were 0.07–3.96, 0.27–4.53, 0.48–5.40, and 0.69–5.78 mIU/L for TSH and 9.16–18.12, 8.67–16.21, 7.80–13.90, and 8.24–16.61 pmol/L for FT4, respectively. Conclusion. The trimester- and assay-specific RIs of thyroid function during pregnancy differed between trimesters, which suggests that it is advisable to detect and avoid misclassification of thyroid dysfunction during pregnancy for women in Henan, China. Jinfang Xing, Enwu Yuan, Jing Li, Yuchao Zhang, Xiangying Meng, Xia Zhang, Shouhua Rong, Zhongxing Lv, Yuan Tian, and Liting Jia Copyright © 2016 Jinfang Xing et al. All rights reserved. The Clinical and Pathological Presentation of Thyroid Nodules in Children and the Comparison with Adult Population: Experience of a Single Institution Sun, 20 Mar 2016 09:50:40 +0000 The clinical and pathological presentation of thyroid nodules among younger and adult patients was compared in an iodine-deficient (ID) region. Data of 3,010 consecutive patients younger than 20 years and 3,010 patients older than 20 years were compared. The proportion of nodular goiters (22.8% versus 39.3%), the ratio of surgically treated nodules (33.2% versus 15.2%), and the proportion of malignant nodules (4.3% versus 2.1%) among diseased patients differed significantly between the two groups (younger versus adult). Nine papillary and 1 medullary carcinoma were found among children, while 15 papillary, 2 follicular, 1 insular, 1 anaplastic, and 1 medullary carcinomas occurred among adults. The ratio of follicular adenoma to hyperplastic nodules (3 : 1 to 1 : 1.67), the proportion of follicular variant (77.8% versus 26.7%), T4 tumors (77.8% versus 33.3%), and tumors with lymph node metastasis (88.9% versus 66.7%) were significantly higher among younger papillary carcinoma patients. No malignancies occurred among spongiform and central type cysts. Similarly to iodine-sufficient regions, more nodules are malignant and carcinomas have a clinically more aggressive presentation in children in comparison with adult patients in ID. Taking the significantly greater proportion of adenomas and the lack of follicular carcinoma into account, a conservative approach has to be considered in follicular tumors among children. Tamas Solymosi, Gyula Lukacs Toth, Laszlo Budai, and Istvan Gal Copyright © 2016 Tamas Solymosi et al. All rights reserved. The Influence of Alcohol Consumption in Conjunction with Sex Hormone Deficiency on Ca/P Ratio in Rats Thu, 17 Mar 2016 14:12:29 +0000 Deficiency of sex hormones and excessive alcohol consumption are factors that have been related to alterations in the pattern of bone mineralization and osteoporosis. The aim of this study was to evaluate possible alterations in the calcium/phosphorus (Ca/P) ratio in the femur of rats subjected to sex hormone deficiency and/or alcohol consumption. Methods. Female and male Wistar rats () were divided into ovariectomized (Ovx), orchiectomized (Orx), or sham-operated groups and subdivided according to diet: alcoholic diet (20% alcohol solution), isocaloric diet, and ad libitum diet. The diets were administered for 8 weeks. The Ca/P ratio in the femur was analyzed by energy dispersive micro-X-ray spectrometer (μEDX). Results. Consumption of alcohol reduced the Ca/P ratio in both females and males. The isocaloric diet reduced the Ca/P ratio in females. In groups with the ad libitum diet, the deficiency of sex hormones did not change the Ca/P ratio in females or males. However, the combination of sex hormone deficiency and alcoholic diet presented the lowest values for the Ca/P ratio in both females and males. Conclusions. There was a reduced Ca/P ratio in the femur of rats that consumed alcohol, which was exacerbated when combined with a deficiency of sex hormones. Karina Bortolin Lodi, Adriana Mathias Pereira da Silva Marchini, Ana Maria do Espírito Santo, Sigmar de Mello Rode, Leonardo Marchini, and Rosilene Fernandes da Rocha Copyright © 2016 Karina Bortolin Lodi et al. All rights reserved. Robotic versus Open Thyroidectomy for Differentiated Thyroid Cancer: An Evidence-Based Review Wed, 16 Mar 2016 07:38:54 +0000 While open thyroidectomy (OT) is advocated as the gold standard treatment for differentiated thyroid cancer, the contemporary use of robotic thyroidectomy (RT) is often controversial. Although RT combines the unique benefits of the surgical robot and remote access thyroidectomy, its applicability on cancer patients is challenged by the questionable oncological benefits and safety. This review aims to analyze the current literature evidence in comparing RT to OT on thyroid cancers for their perioperative and oncological outcomes. To date, no randomized controlled trial is available in comparing RT to OT. All published studies are nonrandomized or retrospective comparisons. Current data suggests that RT compares less favorably than OT for longer operative time, higher cost, and possibly inferior oncological control with lower number of central lymph nodes retrieved. In terms of morbidity, quality of life outcomes, and short-term recurrence rates, RT and OT are comparable. While conventional OT continues to be appropriate for most thyroid cancers, RT should better be continued by expert surgeons on selected patients who have low-risk thyroid cancers and have high expectations on cosmetic outcomes. Future research should embark on prospective randomized studies for unbiased comparisons. Long-term follow-up studies are also needed to evaluate outcomes on recurrence and survival. Shirley Yuk Wah Liu and Enders Kwok Wai Ng Copyright © 2016 Shirley Yuk Wah Liu and Enders Kwok Wai Ng. All rights reserved.