International Journal of Endocrinology The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. The Importance of the Prenyl Group in the Activities of Osthole in Enhancing Bone Formation and Inhibiting Bone Resorption In Vitro Thu, 24 Jul 2014 08:35:34 +0000 Osteoporosis treatment always aimed at keeping the balance of bone formation and bone resorption. Recently, prenyl group in natural products has been proposed as an active group to enhance the osteogenesis process. Osthole has both the prenyl group and bone-protective activities, but the relationship is still unknown. In this study we found that osthole exerted a potent ability to promote proliferation and osteogenic function of rat bone marrow stromal cells and osteoblasts, including improved cell viability, alkaline phosphatase activity, enhanced secretion of collagen-I, bone morphogenetic protein-2, osteocalcin and osteopontin, stimulated mRNA expression of insulin-like growth factor-1, runt-related transcription factor-2, osterix, OPG (osteoprotegerin), RANKL (receptor activator for nuclear factor-B ligand), and the ratio of OPG/RANKL, as well as increasing the formation of mineralized nodules. However, 7-methoxycoumarin had no obvious effects. Osthole also inhibited osteoclastic bone resorption to a greater extent than 7-methoxycoumarin, as shown by a lower tartrate-resistant acid phosphatase activity and lower number and smaller area of resorption pits. Our findings demonstrate that osthole could be a potential agent to stimulate bone formation and inhibit bone resorption, and the prenyl group plays an important role in these bone-protective effects. Yuan-Kun Zhai, Ya-Lei Pan, Yin-Bo Niu, Chen-Rui Li, Xiang-Long Wu, Wu-Tu Fan, Ting-Li Lu, Qi-Bing Mei, and Cory J. Xian Copyright © 2014 Yuan-Kun Zhai et al. All rights reserved. Baicalein Protects against Type 2 Diabetes via Promoting Islet β-Cell Function in Obese Diabetic Mice Wed, 23 Jul 2014 09:48:22 +0000 In both type 1 (T1D) and type 2 diabetes (T2D), the deterioration of glycemic control over time is primarily caused by an inadequate mass and progressive dysfunction of β-cell, leading to the impaired insulin secretion. Here, we show that dietary supplementation of baicalein, a flavone isolated from the roots of Chinese herb Scutellaria baicalensis, improved glucose tolerance and enhanced glucose-stimulated insulin secretion (GSIS) in high-fat diet (HFD-) induced middle-aged obese mice. Baicalein had no effect on food intake, body weight gain, circulating lipid profile, and insulin sensitivity in obese mice. Using another mouse model of type 2 diabetes generated by high-fat diet (HFD) feeding and low doses of streptozotocin injection, we found that baicalein treatment significantly improved hyperglycemia, glucose tolerance, and blood insulin levels in these middle-aged obese diabetic mice, which are associated with the improved islet β-cell survival and mass. In the in vitro studies, baicalein significantly augmented GSIS and promoted viability of insulin-secreting cells and human islets cultured either in the basal medium or under chronic hyperlipidemic condition. These results demonstrate that baicalein may be a naturally occurring antidiabetic agent by directly modulating pancreatic β-cell function. Yu Fu, Jing Luo, Zhenquan Jia, Wei Zhen, Kequan Zhou, Elizabeth Gilbert, and Dongmin Liu Copyright © 2014 Yu Fu et al. All rights reserved. Effect of GH/IGF-1 on Bone Metabolism and Osteoporsosis Wed, 23 Jul 2014 08:15:01 +0000 Background. Growth hormone (GH) and insulin-like growth factor (IGF-1) are fundamental in skeletal growth during puberty and bone health throughout life. GH increases tissue formation by acting directly and indirectly on target cells; IGF-1 is a critical mediator of bone growth. Clinical studies reporting the use of GH and IGF-1 in osteoporosis and fracture healing are outlined. Methods. A Pubmed search revealed 39 clinical studies reporting the effects of GH and IGF-1 administration on bone metabolism in osteopenic and osteoporotic human subjects and on bone healing in operated patients with normal GH secretion. Eighteen clinical studies considered the effect with GH treatment, fourteen studies reported the clinical effects with IGF-1 administration, and seven related to the GH/IGF-1 effect on bone healing. Results. Both GH and IGF-1 administration significantly increased bone resorption and bone formation in the most studies. GH/IGF-1 administration in patients with hip or tibial fractures resulted in increased bone healing, rapid clinical improvements. Some conflicting results were evidenced. Conclusions. GH and IGF-1 therapy has a significant anabolic effect. GH administration for the treatment of osteoporosis and bone fractures may greatly improve clinical outcome. GH interacts with sex steroids in the anabolic process. GH resistance process is considered. Vittorio Locatelli and Vittorio E. Bianchi Copyright © 2014 Vittorio Locatelli and Vittorio E. Bianchi. All rights reserved. Association between Serum Uric Acid Level and Metabolic Syndrome and Its Sex Difference in a Chinese Community Elderly Population Wed, 23 Jul 2014 00:00:00 +0000 Objective. This study aimed to evaluate the association between serum uric acid (SUA) levels within a normal to high range and the risk of metabolic syndrome (MetS) among community elderly and explore the sex difference. Design and Methods. A cross-sectional study was conducted in a representative urban area of Beijing between 2009 and 2010. A two-stage stratified clustering sampling method was used and 2102 elderly participants were included. Results. The prevalence of hyperuricemia and MetS was 16.7% and 59.1%, respectively. There was a strong association between hyperuricemia and four components of MetS in women and three components in men. Multiple logistic regression analysis showed ORs of hyperuricemia for MetS were 1.67 (95% CI: 1.11–2.50) in men and 2.73 (95% CI: 1.81–4.11) in women. Even in the normal range, the ORs for MetS increased gradually according to SUA levels. MetS component number also showed an increasing trend across SUA quartile in both sexes (P for trend < 0.01). Conclusion. This study suggests that higher SUA levels, even in the normal range, are positively associated with MetS among Chinese community elderly, and the association is stronger in women than men. Physicians should recognize MetS as a frequent comorbidity of hyperuricemia and take early action to prevent subsequent disease burden. Miao Liu, Yao He, Bin Jiang, Lei Wu, Shanshan Yang, Yiyan Wang, and Xiaoying Li Copyright © 2014 Miao Liu et al. All rights reserved. Leptin Effects on the Regenerative Capacity of Human Periodontal Cells Tue, 22 Jul 2014 12:01:52 +0000 Obesity is increasing throughout the globe and characterized by excess adipose tissue, which represents a complex endocrine organ. Adipose tissue secrets bioactive molecules called adipokines, which act at endocrine, paracrine, and autocrine levels. Obesity has recently been shown to be associated with periodontitis, a disease characterized by the irreversible destruction of the tooth-supporting tissues, that is, periodontium, and also with compromised periodontal healing. Although the underlying mechanisms for these associations are not clear yet, increased levels of proinflammatory adipokines, such as leptin, as found in obese individuals, might be a critical pathomechanistic link. The objective of this study was to examine the impact of leptin on the regenerative capacity of human periodontal ligament (PDL) cells and also to study the local leptin production by these cells. Leptin caused a significant downregulation of growth (TGFβ1, and VEGFA) and transcription (RUNX2) factors as well as matrix molecules (collagen, and periostin) and inhibited SMAD signaling under regenerative conditions. Moreover, the local expression of leptin and its full-length receptor was significantly downregulated by inflammatory, microbial, and biomechanical signals. This study demonstrates that the hormone leptin negatively interferes with the regenerative capacity of PDL cells, suggesting leptin as a pathomechanistic link between obesity and compromised periodontal healing. Marjan Nokhbehsaim, Sema Keser, Andressa Vilas Boas Nogueira, Andreas Jäger, Søren Jepsen, Joni Augusto Cirelli, Christoph Bourauel, Sigrun Eick, and James Deschner Copyright © 2014 Marjan Nokhbehsaim et al. All rights reserved. The TG/HDL-C Ratio Might Be a Surrogate for Insulin Resistance in Chinese Nonobese Women Mon, 21 Jul 2014 06:56:33 +0000 Obejective. To examine the discriminatory power of triglyceride (TG) and triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) for insulin resistance (IR) in a normoglycaemic Chinese population. Methods. The data were collected from 711 individuals. The normoglycaemic individuals were eventually included in the study (n = 533, age: 62.8 ± 6.6 years, male: 56.8%), who were with a fasting plasma glucose < 6.1 mmol/L and without a history of diabetes. IR was defined as the upper quintile (≥1.6) of homeostasis model assessment of IR. Area under the receiver operating characteristic curve (AROC) was used to examine the discriminatory power. Results. The discriminatory power of TG/HDL-C for IR was acceptable in women with a BMI < 24 kg/m2 or waist circumference < 80 cm (AROCs: 0.718 and 0.713, resp.); however, the discriminatory power was not acceptable in the obese women. TG/HDL-C was not an acceptable marker of IR in men. The discriminatory power of TG for IR was not acceptable in both men and women. Conclusions. The discriminatory power of TG/HDL-C for IR differs by gender and obesity index in the normoglycaemic Chinese population, and TG/HDL-C could discriminate IR in the nonobese and normoglycaemic women. Jiyun He, Sen He, Kai Liu, Yong Wang, Di Shi, and Xiaoping Chen Copyright © 2014 Jiyun He et al. All rights reserved. Increased Incidence of Thyroid Dysfunction and Autoimmunity in Patients with Vernal Keratoconjunctivitis Sun, 20 Jul 2014 12:15:05 +0000 Hormones may play a role in the pathophysiology of vernal keratoconjunctivitis (VKC). An increased incidence of thyroid autoantibodies was recently observed in VKC, although there were no data on thyroid function. Two hundred and eighty-eight patients (202 males, 86 females; range 5.5 to 16.9 years) with VKC were evaluated and compared with 188 normal age- and sex-matched subjects. In all subjects, serum concentrations of free T4, TSH, thyroperoxidase, thyroglobulin, and TSHr autoantibodies were evaluated. In VKC, the family history of thyroid diseases showed no significant differences compared to the controls (9.4 versus 8.6%), whereas the family history of autoimmune diseases was significantly higher (13.2% versus 6.3%; ). Subclinical hypothyroidism was diagnosed in 6.6% (versus 1.6% of the controls; ) and overt hypothyroidism in 0.7% (versus 0.0% of the controls; ). Finally, 5.2% of patients were positive for thyroid autoantibodies, which were significantly higher with respect to the controls (0.5%, ). In the patients positive for thyroid autoantibodies, 80% showed a sonography pattern that suggested autoimmune thyroiditis. Thyroid function and autoimmunity abnormalities are frequently present in children with VKC. Children with VKC should be screened for thyroid function and evaluated for thyroid autoimmunity. Stefano Stagi, Neri Pucci, Laura Di Grande, Cinzia de Libero, Roberto Caputo, Stefano Pantano, Ivan Mattei, Francesca Mori, Maurizio de Martino, and Elio Novembre Copyright © 2014 Stefano Stagi et al. All rights reserved. Cannabinoid Receptor 1 Gene Polymorphisms and Nonalcoholic Fatty Liver Disease in Women with Polycystic Ovary Syndrome and in Healthy Controls Thu, 17 Jul 2014 10:08:48 +0000 Context. Polycystic ovary syndrome (PCOS) is frequently associated with nonalcoholic fatty liver disease (NAFLD). The endocannabinoid system may play a crucial role in the pathogenesis of NAFLD. Polymorphism of the cannabinoid receptor 1 gene (CNR1) may be responsible for individual susceptibility to obesity and related conditions. Objective. To determine the role of genetic variants of CNR1 in the etiopathology of NAFLD in women with PCOS. Design and Setting. Our department (a tertiary referral center) conducted a cross-sectional, case-controlled study. Subjects. 173 women with PCOS (aged 20–35) and 125 healthy, age- and weight-matched controls were studied. Methods. Hepatic steatosis was assessed by ultrasound evaluation. Single nucleotide polymorphisms of CNR1 (rs806368, rs12720071, rs1049353, rs806381, rs10485170, rs6454674) were genotyped. Results. Frequency of the G allele of rs806381 () and the GG genotype of rs10485170 () was significantly higher in women with PCOS and NAFLD than in PCOS women without NAFLD. Frequency of the TT genotype of rs6454674 was higher in PCOS women with NAFLD (not significantly, ). In multivariate stepwise regression, allele G of rs806381 was associated with PCOS + NAFLD phenotype. Conclusion. Our preliminary results suggest the potential role of CNR1 polymorphisms in the etiology of NAFLD, especially in PCOS women. Justyna Kuliczkowska Plaksej, Lukasz Laczmanski, Andrzej Milewicz, A. Lenarcik-Kabza, Anna Trzmiel-Bira, Urszula Zaleska-Dorobisz, Felicja Lwow, and Lidia Hirnle Copyright © 2014 Justyna Kuliczkowska Plaksej et al. All rights reserved. Coronary Heart Disease in Postmenopausal Women with Type II Diabetes Mellitus and the Impact of Estrogen Replacement Therapy: A Narrative Review Thu, 17 Jul 2014 06:31:11 +0000 Coronary heart disease is the main cause of death in postmenopausal women (PMW); moreover its mortality exceeds those for breast cancer in women at all ages. Type II diabetes mellitus is a major cardiovascular risk factor and there is some evidence that the risk conferred by diabetes is greater in women than in men. It was established that the deficiency of endogenous estrogens promotes the atherosclerosis process. However, the impact of estrogen replacement therapy (ERT) on cardiovascular prevention remains controversial. Some authors strongly recommend it, whereas others revealed a concerning trend toward harm. This review tries to underlines the different components of cardiovascular risk in diabetic PMW and to define the place of ERT. Marouane Boukhris, Salvatore Davide Tomasello, Francesco Marzà, Sonia Bregante, Francesca Romana Pluchinotta, and Alfredo Ruggero Galassi Copyright © 2014 Marouane Boukhris et al. All rights reserved. The Alliance of Mesenchymal Stem Cells, Bone, and Diabetes Wed, 16 Jul 2014 16:26:07 +0000 Bone fragility has emerged as a new complication of diabetes. Several mechanisms in diabetes may influence bone homeostasis by impairing the action between osteoblasts, osteoclasts, and osteocytes and/or changing the structural properties of the bone tissue. Some of these mechanisms can potentially alter the fate of mesenchymal stem cells, the initial precursor of the osteoblast. In this review, we describe the main factors that impair bone health in diabetic patients and their clinical impact. Nicola Napoli, Rocky Strollo, Angela Paladini, Silvia I. Briganti, Paolo Pozzilli, and Sol Epstein Copyright © 2014 Nicola Napoli et al. All rights reserved. MTNR1B Genetic Variability Is Associated with Gestational Diabetes in Czech Women Tue, 15 Jul 2014 06:50:55 +0000 The gene MTNR1B encodes a receptor for melatonin. Melatonin receptors are expressed in human β-cells, which implies that genetic variants might affect glucose tolerance. Meta-analysis confirmed that the rs10830963 shows the most robust association. The aim of the study was to assess the rs10830963 in Czech GDM patients and controls and to study relations between the SNP and biochemical as well as anthropometric characteristics. Our cohort consisted of 880 women; 458 were diagnosed with GDM, and 422 were normoglycemic controls without history of GDM. Despite similar BMI, the GDM group showed higher WHR, waist circumference, abdominal circumference, and total body fat content. The risk allele G was more frequent in the GDM group (38.3 versus 29.4% in controls, OR 1.49 CI95% [1.22; 1.82]; ). In spite of higher frequency, the G allele in the GDM group was not associated with any markers of glucose metabolism. In contrast, controls showed significant association of the allele G with FPG and with postchallenge glycemia during the oGTT. Frequency analysis indicates that rs10830963 is involved in gestational diabetes in Czech women. However, the association of the SNP with glucose metabolism, which is obvious in controls, is covert in women who have experienced GDM. Daniela Vejrazkova, Petra Lukasova, Marketa Vankova, Josef Vcelak, Olga Bradnova, Veronika Cirmanova, Katerina Andelova, Hana Krejci, and Bela Bendlova Copyright © 2014 Daniela Vejrazkova et al. All rights reserved. Laparoscopic Adrenalectomy for Adrenal Tumors Tue, 15 Jul 2014 00:00:00 +0000 Objective. To evaluate the indication and the clinical value of laparoscopic adrenalectomy of different types of adrenal tumor. Methods. From 2009 to 2014, a total of 110 patients were diagnosed with adrenal benign tumor by CT scan and we performed laparoscopic adrenalectomy. The laparoscopic approach has been the procedure of choice for surgery of benign adrenal tumors, and the upper limit of tumor size was thought to be 6 cm. Results. 109 of 110 cases were successful; only one was converted to open surgery due to bleeding. The average operating time and intraoperative blood loss of pheochromocytoma were significantly more than the benign tumors (). After 3 months of follow-up, the preoperative symptoms were relieved and there was no recurrence. Conclusions. Laparoscopic adrenalectomy has the advantages of minimal invasion, less blood loss, fewer complications, quicker recovery, and shorter hospital stay. The full preparation before operation can decrease the average operating time and intraoperative blood loss of pheochromocytomas. Laparoscopic adrenalectomy should be considered as the first choice treatment for the resection of adrenal benign tumor. Sun Chuan-yu, Ho Yat-faat, Ding Wei-hong, Gou Yuan-cheng, Hu Qing-feng, Xu Ke, Gu Bin, and Xia Guo-wei Copyright © 2014 Sun Chuan-yu et al. All rights reserved. FBP1 Is an Interacting Partner of Menin Mon, 14 Jul 2014 12:34:19 +0000 Multiple endocrine neoplasia type 1 (MEN1) is a syndrome characterized by tumors in multiple endocrine tissues such as the parathyroid glands, the pituitary gland, and the enteropancreatic neuroendocrine tissues. MEN1 is usually caused by mutations in the MEN1 gene that codes for the protein menin. Menin interacts with proteins that regulate transcription, DNA repair and processing, and maintenance of cytoskeletal structure. We describe the identification of FBP1 as an interacting partner of menin in a large-scale pull-down assay that also immunoprecipitated RBBP5, ASH2, and LEDGF, which are members of complex proteins associated with SET1 (COMPASS), a protein complex that methylates histone H3. This interaction was confirmed by coimmunoprecipitation and Flag-pull-down assays. Furthermore, menin localized to the FUSE site on the MYC promoter, a site that is transactivated by FBP1. This investigation therefore places menin in a pathway that regulates MYC gene expression and has important implications for the biological function of menin. Shadia Zaman, Karen Sukhodolets, Patricia Wang, Jun Qin, David Levens, Sunita K. Agarwal, and Stephen J. Marx Copyright © 2014 Shadia Zaman et al. All rights reserved. Fasting Hyperglycemia Increases In-Hospital Mortality Risk in Nondiabetic Female Patients with Acute Myocardial Infarction: A Retrospective Study Mon, 14 Jul 2014 10:19:24 +0000 Previous studies had shown that elevated admission plasma glucose (APG) could increase mortality rate and serious complications of acute myocardial infarction (AMI), but whether fasting plasma glucose (FPG) had the same role remains controversial. In this retrospective study, 253 cases of AMI patients were divided into diabetic () and nondiabetic group (). Our results showed that: compared with the nondiabetic patients, diabetic patients had higher APG, FPG, higher plasma triglyceride, higher rates of painless AMI (), non-ST-segment elevation myocardial infarction (NSTEMI), and reinfraction (). They also had lower high density lipoprotein cholesterol and rate of malignant arrhythmia, but in-hospital mortality rate did not differ significantly (). While nondiabetic patients were subgrouped in terms of APG and FPG (cut points were 11.1 mmol/L and 7.0 mmol/L, resp.), the mortality rate had significant difference (), whereas glucose level lost significance in diabetic group. Multivariate logistic regression analysis showed that FPG (OR: 2.014; 95% confidence interval: 1.296–3.131; ) but not APG was independent predictor of in-hospital mortality for nondiabetic patients. These results indicate that FPG can be an independent predictor for mortality in nondiabetic female patients with AMI. Guojing Luo, Hong Liu, Shunkui Luo, Fang Li, Minhong Su, and Hongyun Lu Copyright © 2014 Guojing Luo et al. All rights reserved. ATP Synthase β-Chain Overexpression in SR-BI Knockout Mice Increases HDL Uptake and Reduces Plasma HDL Level Thu, 10 Jul 2014 09:55:42 +0000 HDL cholesterol is known to be inversely correlated with cardiovascular disease due to its diverse antiatherogenic functions. SR-BI mediates the selective uptake of HDL-C. SR-BI knockout diminishes but does not completely block the transport of HDL; other receptors may be involved. Ectopic ATP synthase β-chain in hepatocytes has been previously characterized as an apoA-I receptor, triggering HDL internalization. This study was undertaken to identify the overexpression of ectopic ATP synthase β-chain on DIL-HDL uptake in primary hepatocytes in vitro and on plasma HDL levels in SR-BI knockout mice. Human ATP synthase β-chain cDNA was delivered to the mouse liver by adenovirus and GFP adenovirus as control. The adenovirus-mediated overexpression of β-chain was identified at both mRNA and protein levels on mice liver and validated by its increasing of DiL-HDL uptake in primary hepatocytes. In response to hepatic overexpression of β-chain, plasma HDL-C levels and cholesterol were reduced in SR-BI knockout mice, compared with the control. The present data suggest that ATP synthase β-chain can serve as the endocytic receptor of HDL, and its overexpression can reduce plasma HDL-C. Kexiu Song, Yingchun Han, Linhua Zhang, Guoqing Liu, Peng Yang, Xiaoyun Cheng, Le Bu, Hui Sheng, and Shen Qu Copyright © 2014 Kexiu Song et al. All rights reserved. The Association between IGF-1 Polymorphisms, IGF-1 Serum Levels, and Cognitive Functions in Healthy Adults: The Amsterdam Growth and Health Longitudinal Study Thu, 10 Jul 2014 08:03:01 +0000 Several studies have demonstrated an association between polymorphisms in the insulin-like growth factor-1 (IGF-1) gene and IGF-1 serum levels. IGF-1 levels have been associated with cognitive functioning in older persons and growth hormone deficient patients. The present study investigates whether IGF-1 polymorphisms, IGF-1 levels, and cognition are interconnected in healthy adults. Data of 277 participants (mean age: 42.4 years) of the Amsterdam Growth and Health Longitudinal Study on IGF-1 promoter polymorphisms, IGF-1 serum level, spatial working memory (SWM), paired associate learning (PAL), and IQ tests were analyzed. (M)ANOVAs were applied to confirm the associations between IGF-1 polymorphisms and IGF-1 levels and between IGF-1 levels and cognition. Three groups were distinguished based on specific IGF-1 polymorphism alleles: a homozygote 192 bp/192 bp genotype, a heterozygote 192 bp/x genotype, and a noncarrier x/x genotype. Although different IGF-1 levels were found for the three genotypes, performance on all cognitive tasks and IQ measures was similar. Despite the associations between IGF-1 polymorphisms and IGF-1 levels, no association was found between cognition and IGF-1 levels. It seems that IGF-1 does not play a role in the cognitive performance of healthy middle-aged adults. Possible, IGF-1 fulfills a more developmental and protective role in cognition which becomes apparent during childhood, old-age, or disease. Carmilla M. M. Licht, Lise C. van Turenhout, Jan Berend Deijen, Lando L. J. Koppes, Willem van Mechelen, Jos W. R. Twisk, and Madeleine L. Drent Copyright © 2014 Carmilla M. M. Licht et al. All rights reserved. Body Mass Index Is Associated with Hypercholesterolemia following Thyroid Hormone Withdrawal in Thyroidectomized Patients Wed, 09 Jul 2014 09:33:05 +0000 Thyroid hormone withdrawal (THW) for postoperative radioiodine adjuvant therapy or diagnostic radioiodine whole body scan in patients with differentiated thyroid cancers results in acute thyroid hormone deficiency and abnormal lipid profiles. To better clarify the clinical pattern of dyslipidemia occurring after THW, we retrospectively analyzed the association between serum total cholesterol level after THW and various clinical factors in a total of 61 patients who underwent total thyroidectomy due to papillary thyroid cancers from January 2010 to March 2012, in Severance Hospital, Seoul, Korea. Preoperative baseline total cholesterol was significantly correlated with post-THW total cholesterol level; however, age, gender, or elevated TSH level after THW itself was not correlated with post-THW total cholesterol level. A significant correlation between preoperative measured BMI and post-THW total cholesterol level was found (). In multiple logistic analysis, BMI was an independent determining factor of post-THW total cholesterol level (). Dong Yeob Shin, Kwang Joon Kim, Yongin Cho, Kyeong Hye Park, Sena Hwang, Woong Youn Chung, and Eun Jig Lee Copyright © 2014 Dong Yeob Shin et al. All rights reserved. Response to Initial Therapy of Differentiated Thyroid Cancer Predicts the Long-Term Outcome Better than Classical Risk Stratification Systems Tue, 08 Jul 2014 00:00:00 +0000 Objective. Although differentiated thyroid cancer (DTC) usually has an indolent course, some cases show a poor prognosis; therefore, risk stratification is required. The objective of this study is to compare the predictive ability of classical risk stratification systems proposed by the European Thyroid Association (ETA) and American Thyroid Association (ATA) with the system proposed by Tuttle et al. in 2010, based on the response to initial therapy (RIT). Methods. We retrospectively reviewed 176 cases of DTC with a median follow-up period of 7.0 years. Each patient was stratified using ETA, ATA, and RIT systems. Negative predictive value (NPV) and positive predictive value (PPV) were determined. The area under receiver operating characteristic (ROC) curve was calculated in order to compare the predictive ability. Results. RIT showed a NPV of 97.7%, better than NPV of ETA and ATA systems (93.9% and 94.9%, resp.). ETA and ATA systems showed poor PPV (40.3% and 41%, resp.), while RIT showed a PPV of 70.8%. The area under ROC curve was 0.7535 for ETA, 0.7876 for ATA, and 0.9112 for RIT, showing statistical significant differences . Conclusions. RIT predicts the long-term outcome of DTC better than ETA/ATA systems, becoming a useful system to adapt management strategies. Albert Cano-Palomares, Ignasi Castells, Ismael Capel, Maria Rosa Bella, Santi Barcons, Angel Serrano, Xavier Guirao, and Mercedes Rigla Copyright © 2014 Albert Cano-Palomares et al. All rights reserved. Serum 25-OH Vitamin D in relation to Bone Mineral Density and Bone Turnover Mon, 07 Jul 2014 12:16:18 +0000 It is unclear which vitamin D status is optimal for bone health. In this study, we aimed to assess cutoffs of 25-hydroxyvitamin D (25OHD) derived by the literature (20, 25, or 30 ng/mL) in relation to bone turnover and bone mineral density (BMD). Serum 25OHD, PTH, osteocalcin, bone alkaline phosphatase, and C-telopeptide were measured in 274 consecutive postmenopausal women. BMD of the lumbar spine (L1–L4) and of femoral neck were also evaluated. 50 patients had normal BMD, while 124 had osteopenia and 100 had osteoporosis. 37.6%, 56.2%, and 70.8% subjects had serum 25OHD lower than 20, 25, or 30 ng/mL, respectively. No differences in bone turnover markers were found when comparing patients with low 25OHD defined according to the different cutoffs. However, a cutoff of 25 ng/mL appeared to differentiate better than a cutoff of 30 ng/mL in those subjects with reduced femoral neck BMD. The PTH plateau occurred at 25OHD levels of 26–30 ng/mL. In conclusion, vitamin D deficiency is common in Sicilian postmenopausal women and it may be associated with low BMD and increased bone turnover markers. Further studies are needed to better define the right cutoff for normal vitamin D levels in postmenopausal women. Nicola Napoli, Rocky Strollo, Delia Sprini, Ernesto Maddaloni, Giovam Battista Rini, and Enrico Carmina Copyright © 2014 Nicola Napoli et al. All rights reserved. High Glucose Aggravates the Detrimental Effects of Pancreatic Stellate Cells on Beta-Cell Function Thu, 03 Jul 2014 00:00:00 +0000 Background and Aims. We here assess the effects of PSCs on β-cell function and apoptosis in vivo and in vitro. Materials and Methods. PSCs were transplanted into Wistar and Goto-Kakizaki (GK) rats. Sixteen weeks after transplantation, β-cell function, apoptosis, and islet fibrosis were assessed. In vitro the effects of PSCs conditioned medium (PSCs-CM) and/or high concentration of glucose on INS-1 cell function was assessed by measuring insulin secretion, INS-1 cell survival, apoptosis, and endoplasmic reticulum stress (ER stress) associated CHOP expression. Results. PSCs transplantation exacerbated the impaired β-cell function in GK rats, but had no significant effects in Wistar rats. In vitro, PSCs-CM caused impaired INS-1 cell viability and insulin secretion and increased apoptosis, which were more pronounced in the presence of high glucose. Conclusion. Our study demonstrates that PSCs induce β-cell failure in vitro and in vivo. Min Zha, Wei Xu, Qing Zhai, Fengfei Li, Bijun Chen, and Zilin Sun Copyright © 2014 Min Zha et al. All rights reserved. Testosterone and Adipokines are Determinants of Physical Performance, Strength, and Aerobic Fitness in Frail, Obese, Older Adults Wed, 02 Jul 2014 11:51:38 +0000 In this study, we evaluated the independent and combined effects of baseline circulating gonadal, anabolic hormones and adipokines on physical function in 107 frail, obese (BMI ≥ 30 kg/m2), and older (≥65 yr) subjects. Our results showed significant positive correlations between circulating testosterone and insulin growth factor-1 (IGF-1) with knee flexion, knee extension, one-repetition maximum (1-RM), and peak oxygen consumption (VO2 peak), while no correlation was observed with estradiol. Among the adipokines, high sensitivity C-reactive protein (Hs-CRP) and leptin negatively correlated with the modified physical performance testing (PPT), knee flexion, knee extension, 1-RM, and VO2 peak. Interleukin-6 ( Il-6) negatively correlated with knee flexion and VO2 peak and soluble tumor necrosis factors receptor-1 (sTNFr1) correlated with PPT, 1-RM, and VO2 peak. Adiponectin correlated negatively with 1-RM. Multiple regression analysis revealed that, for PPT, sTNFr1 was the only independent predictor. Independent predictors included adiponectin, leptin, and testosterone for knee flexion; leptin and testosterone for knee extension; adiponectin, leptin, and testosterone for 1-RM; and IGF-1, IL-6, leptin, and testosterone for VO2 peak. In conclusion, in frail obese older adults, circulating levels of testosterone, adiponectin, and leptin appear to be important predictors of physical strength and fitness, while inflammation appears to be a major determinant of physical frailty. Lina E. Aguirre, Irum Zeb Jan, Kenneth Fowler, Debra L. Waters, Dennis T. Villareal, and Reina Armamento-Villareal Copyright © 2014 Lina E. Aguirre et al. All rights reserved. Anaplastic Thyroid Carcinoma: Current Treatments and Potential New Therapeutic Options with Emphasis on TfR1/CD71 Tue, 01 Jul 2014 13:34:23 +0000 Anaplastic thyroid carcinoma (ATC) is one of the most aggressive human cancers. Actually, ATC is refractory to conventional therapies, including surgery, chemotherapy, radiotherapy, and radioiodine (131I) therapy. Accordingly, genetic and molecular characterizations of ATC have been frequently and periodically reviewed in order to identify potential biological markers exploitable for target therapy. This review briefly focuses on main molecular events that characterize ATC and provides an update about preclinical studies. In addition, the overexpression of transferrin receptor 1 (TfR1/CD71) by neoplastic cells of ATC is emphasized in that it could represent a potential therapeutic target. In this regard, new therapeutic approaches based on the use of monoclonal or recombinant antibodies, or transferrin-gallium-TfR1/CD71 molecular complexes, or lastly small interfering RNAs (siRNAs) are proposed. Rosalba Parenti, Lucia Salvatorelli, and Gaetano Magro Copyright © 2014 Rosalba Parenti et al. All rights reserved. A New Aurora in Anaplastic Thyroid Cancer Therapy Tue, 01 Jul 2014 12:07:21 +0000 Anaplastic thyroid cancers (ATC) are among the most aggressive human neoplasms with a dire prognosis and a median survival time of few months from the diagnosis. The complete absence of effective therapies for ATC renders the identification of novel therapeutic approaches sorely needed. Chromosomal instability, a feature of all human cancers, is thought to represent a major driving force in thyroid cancer progression and a number of mitotic kinases showing a deregulated expression in malignant thyroid tissues are now held responsible for thyroid tumor aneuploidy. These include the three members of the Aurora family (Aurora-A, Aurora-B, and Aurora-C), serine/threonine kinases that regulate multiple aspects of chromosome segregation and cytokinesis. Over the last few years, several small molecule inhibitors targeting Aurora kinases were developed, which showed promising antitumor effects against a variety of human cancers, including ATC, in preclinical studies. Several of these molecules are now being evaluated in phase I/II clinical trials against advanced solid and hematological malignancies. In the present review we will describe the structure, expression, and mitotic functions of the Aurora kinases, their implications in human cancer progression, with particular regard to ATC, and the effects of their functional inhibition on malignant cell proliferation. Enke Baldini, Massimino D’Armiento, and Salvatore Ulisse Copyright © 2014 Enke Baldini et al. All rights reserved. CHADS2 Scores in the Prediction of Major Adverse Cardiovascular Events in Patients with Cushing’s Syndrome Tue, 01 Jul 2014 12:06:13 +0000 Vascular events are one of the major causes of death in case of Cushing’s syndrome (CS). However, due to the relative low frequency of CS, it is hard to perform a risk assessment for these events. As represented congestive heart failure (C), hypertension (H), age (A), diabetes (D), and stroke (S), the CHADS2 score is now accepted to classify the risk of major adverse cardiovascular events (MACEs) in patients with atrial fibrillation. In this study, participants were enrolled from the National Health Research Institute Database (NHIRD) of Taiwan, and we reviewed 551 patients with their sequential clinically diagnosed CS data between 2002 and 2009 in relation to MACEs risk using CHADS2 score. Good correlation could be identified between the CS and CHADS2 score . Our results show that patients with CS show significantly higher risk of vascular events and the CHADS2 score could be applied for MACEs evaluation. Adequate lifestyle modifications and aggressive cardiovascular risks treatment are suggested for CS patients with higher CHADS2 score. Yuh-Feng Wang, Mei-Hua Chuang, Tzyy-Ling Chuang, Kung-Yung Huang, Shaw-Ruey Lyu, Chih-Yuan Huang, and Ching-Chih Lee Copyright © 2014 Yuh-Feng Wang et al. All rights reserved. The Effect of Renal Dysfunction on Circulating Sclerostin Level in Patients with Type 2 Diabetes Thu, 26 Jun 2014 00:00:00 +0000 Objective. Sclerostin is a Wnt inhibitor produced specifically by osteocytes. However, it is not currently clear whether renal dysfunction has an effect on circulating sclerostin level in patients with type 2 diabetes. The aim of the study was to evaluate this relationship. Design and Patients. We conducted a cross-sectional observational study of 302 type 2 diabetic patients with or without chronic kidney disease. Serum sclerostin level was analyzed by ELISA, and renal function was assessed by estimated glomerular filtration rate (eGFR) using chronic kidney disease epidemiology collaboration (CKD-EPI) equation. Results. There was a strong correlation between sclerostin level with renal function presented as serum creatinine (, ) and eGFR (, ). Serum sclerostin level was significantly higher in patients with CKD-G3 stage than those with CKD-G1/2 stages after adjusting for age, sex, and BMI (). Patients with CKD-G4/5 stages had dramatically increased level of circulating sclerostin. Multiple regression analyses found that age, sex, and eGFR were independent determining factors for circulating sclerostin level. Conclusion. Our data showed that serum sclerostin levels start to increase in diabetic patients with CKD-G3 stage. Further studies are needed to establish the potential role of elevated sclerostin in diabetic patients with CKD. Se Hwa Kim, Soo Young Yoon, Sung-Kil Lim, and Yumie Rhee Copyright © 2014 Se Hwa Kim et al. All rights reserved. Prevalence of Amiodarone-Induced Thyrotoxicosis and Associated Risk Factors in Japanese Patients Wed, 25 Jun 2014 11:39:48 +0000 Amiodarone is a widely used agent for life-threatening arrhythmias. Although amiodarone-induced thyrotoxicosis (AIT) is a major adverse effect that can cause recurrence of arrhythmias and exacerbation of heart failure, risk factors for AIT among amiodarone-treated Japanese patients have not been elucidated. Here, we investigated the prevalence and predictive factors for AIT. The study subjects were 225 patients treated with amiodarone between 2008 and 2012, who were euthyroid before amiodarone therapy. All patients with AIT were diagnosed by measurement of thyroid hormones and ultrasonography. Among the 225 subjects, 13 patients (5.8%) developed AIT and all the patients were classified as Type 2 AIT. Baseline features of patients with AIT were not different from those who did not develop AIT, except for age (AIT, 55.1 ± 13.8, non-AIT, 68.1 ± 12.0 years, ). Multivariate analyses using the Cox proportional hazard model identified age as the sole determinant of AIT (hazard ratio: 0.927, 95% confidence interval: 0.891–0.964). Receiver operating characteristic curve analysis identified age of 63.5 years as the cutoff value for AIT with sensitivity of 70.3% and specificity of 69.2%. In summary, this study showed that the prevalence of AIT is 5.8% in Japanese patients treated with amiodarone and that young age is a risk factor for AIT. Toyoyoshi Uchida, Takatoshi Kasai, Atsutoshi Takagi, Gaku Sekita, Koji Komiya, Kageumi Takeno, Nayumi Shigihara, Kazunori Shimada, Katsumi Miyauchi, Yoshio Fujitani, Hiroyuki Daida, and Hirotaka Watada Copyright © 2014 Toyoyoshi Uchida et al. All rights reserved. Vitamin D Binding Protein and Vitamin D Levels Wed, 25 Jun 2014 09:09:47 +0000 Zhongjian Xie, Arthur C. Santora, Sue A. Shapses, and Xiangbing Wang Copyright © 2014 Zhongjian Xie et al. All rights reserved. Erratum to “Meta-Analysis: Overweight, Obesity, and Parkinson’s Disease” Wed, 25 Jun 2014 05:53:52 +0000 Jinhu Chen, Zhenlong Guan, Liqin Wang, Guangyao Song, Boqing Ma, and Yanqin Wang Copyright © 2014 Jinhu Chen et al. All rights reserved. Influence of the A3669G Glucocorticoid Receptor Gene Polymorphism on the Metabolic Profile of Pediatric Patients with Congenital Adrenal Hyperplasia Mon, 23 Jun 2014 07:58:49 +0000 Background. Pediatric CAH patients have an increased risk of cardiovascular disease, and it remains unknown if genetic predisposition is a contributing factor. Glucocorticoid receptor gene (NR3C1) polymorphisms are associated with an adverse metabolic profile. Our aim was to analyze the association between the NR3C1 polymorphisms and the metabolic profile of pediatric CAH patients. Methods. Forty-one patients (26SW/15SV) received glucocorticoid (GC) replacement therapy to achieve normal androgen levels. Obesity was defined by th percentile. NR3C1 alleles were genotyped, and association analyses with phenotype were done with Chi-square, t-test, and multivariate and regression analysis. Results. Obesity was observed in 31.7% of patients and was not correlated with GC doses and treatment duration. Z-score BMI was positively correlated with blood pressure, triglycerides, LDL-c levels, and HOMA-IR. NR3C1 polymorphisms, BclI and A3669G, were found in 23.1% and 9.7% of alleles, respectively. A3669G carriers presented higher LDL-c levels compared to wild-type subjects. BclI-carriers and noncarriers did not differ. Conclusion. Our results suggest that A3669G-polymorphism could be involved with a susceptibility to adverse lipid profile in pediatric CAH patients. This study provides new insight into the GR screening during CAH treatment, which could help to identify the subgroup of at-risk patients who would most benefit from preventive therapeutic action. Ricardo P. P. Moreira, Larissa G. Gomes, Guiomar Madureira, Berenice B. Mendonca, and Tânia A. S. S. Bachega Copyright © 2014 Ricardo P. P. Moreira et al. All rights reserved. Osteoporosis, Fractures, and Diabetes Mon, 23 Jun 2014 07:52:28 +0000 It is well established that osteoporosis and diabetes are prevalent diseases with significant associated morbidity and mortality. Patients with diabetes mellitus have an increased risk of bone fractures. In type 1 diabetes, the risk is increased by ∼6 times and is due to low bone mass. Despite increased bone mineral density (BMD), in patients with type 2 diabetes the risk is increased (which is about twice the risk in the general population) due to the inferior quality of bone. Bone fragility in type 2 diabetes, which is not reflected by bone mineral density, depends on bone quality deterioration rather than bone mass reduction. Thus, surrogate markers and examination methods are needed to replace the insensitivity of BMD in assessing fracture risks of T2DM patients. One of these methods can be trabecular bone score. The aim of the paper is to present the present state of scientific knowledge about the osteoporosis risk in diabetic patient. The review also discusses the possibility of problematic using the study conclusions in real clinical practice. Peter Jackuliak and Juraj Payer Copyright © 2014 Peter Jackuliak and Juraj Payer. All rights reserved.