International Journal of Endocrinology The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Retrospective Analysis of Cushing’s Disease with or without Hyperprolactinemia Sun, 23 Nov 2014 08:15:53 +0000 Objective. We compared the characteristics of patients with Cushing’s disease alone with those of patients with Cushing’s disease and hyperprolactinemia. Methods. Eighty-four patients were enrolled between 2002 and 2011, in a hospital in China. Clinical, endocrinological, and histopathological data, MRI scans, and surgical outcomes were reviewed throughout the follow-up period. Results. Patients with Cushing’s disease and hyperprolactinemia had a younger age at diagnosis (30.28 ± 14.23 versus 36.08 ± 10.91 years; ) and a larger adenoma maximal diameter (2.44 ± 1.32 versus 1.44 ± 1.05 cm; ) than patients with Cushing’s disease alone. Menstrual disorders () and visual field defects () were more common and progressive obesity () and hypertension () were less common in patients with Cushing’s disease and hyperprolactinemia. The rate of normalization of hormonal levels was lower (41.7% versus 91.7%; ) and the recurrence rate was higher (36.1% versus 8.3%; ) in patients with Cushing’s disease and hyperprolactinemia. Conclusions. Careful long-term follow-up is needed of patients with Cushing’s disease and hyperprolactinemia. Cheng Huan, Chao Lu, Guang-ming Xu, Xin Qu, and Yuan-ming Qu Copyright © 2014 Cheng Huan et al. All rights reserved. Ovarian and Adrenal Androgens and Their Link to High Human Chorionic Gonadotropin Levels: A Prospective Controlled Study Sun, 23 Nov 2014 00:00:00 +0000 Background. Although the association between human chorionic gonadotropin (hCG) and hyperandrogenism was identified more than 40 years ago, relevant questions remain unanswered. Design and Methods. We conducted a prospective, longitudinal, and controlled study in 23 women with a diagnosis of a complete hydatidiform mole (HM). Results. All participants completed the study. Before HM evacuation mean hCG was markedly higher in the cases than in the control group (). Free testosterone (T) and dehydroepiandrosterone sulfate (DHEA-S) were found to be higher in the cases (2.78 ± 1.24 pg/mL and 231.50 ± 127.20 μ/dL) when compared to the control group (1.50 ± 0.75 pg/mL and 133.59 ± 60.69 μ/dL) ( and 0.001), respectively. There was a strong correlation between hCG and free T/total T/DHEA-S concentrations (; , ;  , and ;  ), respectively. In the cases group 48 hours after HM evacuation, hCG levels were found to be significantly lower when compared to initial levels () and free T and DHEA-S declined significantly ( and 0.009). Conclusion. Before uterus evacuation, hCG, free T, and DHEA-S levels were significantly higher when compared with controls finding a strong correlation between hCG and free T/DHEA-S levels. Forty-eight hours after HM treatment hCG levels declined and the difference was lost. A novel finding of our study is that in cases, besides free T, DHEA-S was also found to be significantly higher and both the ovaries and adrenal glands appear to be the sites of this androgen overproduction. René Rodríguez-Gutiérrez, Jesús Zacarías Villarreal-Pérez, Felipe Arturo Morales-Martinez, René Rodríguez-Guajardo, Gloria González-Saldivar, Leonardo G. Mancillas-Adame, Neri Alejandro Alvarez-Villalobos, Fernando Javier Lavalle-Gonzalez, and José Gerardo González-González Copyright © 2014 René Rodríguez-Gutiérrez et al. All rights reserved. Coexistence of Histologically Confirmed Hashimoto’s Thyroiditis with Different Stages of Papillary Thyroid Carcinoma in a Consecutive Chinese Cohort Tue, 18 Nov 2014 12:42:03 +0000 Purpose. To determine the relationship between Hashimoto’s thyroiditis (HT) and all stages of papillary thyroid carcinoma (PTC) with or without local lymph node metastasis (LNM). Methods. We conducted a retrospective study of thyroidectomies from 2008–2013 in First Affiliated Hospital of Nanjing Medical University. We categorized patients according to the presence of histopathologically proven HT. The prevalence of mPTC (maximum diameter ≤ 10 mm) and crPTC (clinical relevant PTC) and local LNM rates were compared. Results. We evaluated 6,432 consecutive thyroidectomies. In total, 1,328 specimens were confirmed as HT. The prevalence of PTC in this HT cohort was 43.8%, significantly higher than non-HT group. After adjustment of gender and age, the prevalence of PTC was still higher in HT group. HT was a risk factor for PTC in multivariate analysis with odds ratio 2.725 (95% CI, 2.390–3.109) (). However, no correlation was found between HT and LNM of PTC. Conclusion. HT was associated with an increased prevalence of all stages of PTC, independent of tumor size, gender, and age. In contrast, locally advanced disease defined by LNM was unrelated to HT. These data suggest an association of HT with low risk PTC and a potential protective immunologic effect from further disease progression. Xiaoyun Liu, Lijun Zhu, Dai Cui, Zhixiao Wang, Huanhuan Chen, Yu Duan, Meiping Shen, Yunsong Wu, Rong Rong, Zhihong Zhang, Xiaodong Wang, Jiawei Chen, Erik K. Alexander, and Tao Yang Copyright © 2014 Xiaoyun Liu et al. All rights reserved. Angiogenesis in Pituitary Adenomas: Human Studies and New Mutant Mouse Models Tue, 18 Nov 2014 09:04:53 +0000 The role of angiogenesis in pituitary tumor development has been questioned, as pituitary tumors have been usually found to be less vascularized than the normal pituitary tissue. Nevertheless, a significantly higher degree of vasculature has been shown in invasive or macropituitary prolactinomas when compared to noninvasive and microprolactinomas. Many growth factors and their receptors are involved in pituitary tumor development. For example, VEGF, FGF-2, FGFR1, and PTTG, which give a particular vascular phenotype, are modified in human and experimental pituitary adenomas of different histotypes. In particular, vascular endothelial growth factor, VEGF, the central mediator of angiogenesis in endocrine glands, was encountered in experimental and human pituitary tumors at different levels of expression and, in particular, was higher in dopamine agonist resistant prolactinomas. Furthermore, several anti-VEGF techniques lowered tumor burden in human and experimental pituitary adenomas. Therefore, even though the role of angiogenesis in pituitary adenomas is contentious, VEGF, making permeable pituitary endothelia, might contribute to adequate temporal vascular supply and mechanisms other than endothelial cell proliferation. The study of angiogenic factor expression in aggressive prolactinomas with resistance to dopamine agonists will yield important data in the search of therapeutical alternatives. Carolina Cristina, Guillermina María Luque, Gianina Demarchi, Felicitas Lopez Vicchi, Lautaro Zubeldia-Brenner, Maria Ines Perez Millan, Sofia Perrone, Ana Maria Ornstein, Isabel M. Lacau-Mengido, Silvia Inés Berner, and Damasia Becu-Villalobos Copyright © 2014 Carolina Cristina et al. All rights reserved. Acute Exposure to a Precursor of Advanced Glycation End Products Induces a Dual Effect on the Rat Pancreatic Islet Function Mon, 17 Nov 2014 00:00:00 +0000 Aim. Chronic diseases are the leading cause of death worldwide. Advanced glycation end products, known as AGEs, are a major risk factor for diabetes onset and maintenance. Methylglyoxal (MG), a highly reactive metabolite of glucose, is a precursor for the generation of endogenous AGEs. Methods. In this current study we incubated in vitro pancreatic islets from adult rats in absence or presence of MG (10 μmol/l) with different concentrations of glucose and different metabolic components (acetylcholine, epinephrine, potassium, forskolin, and leucine). Results. Different effects of MG on insulin secretion were evidenced. In basal glucose stimulation (5.6 mM), MG induced a significant () increase of insulin secretion. By contrast, in higher glucose concentrations (8.3 mM and 16.7 mM), MG significantly inhibited insulin secretion (). In the presence of potassium, forskolin, and epinephrine, MG enhanced insulin secretion (), while when it was incubated with acetylcholine and leucine, MG resulted in a decrease of insulin secretion (). Conclusion. We suggest that MG modulates the secretion activity of beta-cell depending on its level of stimulation by other metabolic factors. These results provide insights on a dual acute effect of MG on the pancreatic cells. Ghada Elmhiri, Luiz Felipe Barella, Didier Vieau, Sylvaine Camous, Paulo C. F. Mathias, and Latifa Abdennebi-Najar Copyright © 2014 Ghada Elmhiri et al. All rights reserved. Emerging Targets in Pituitary Adenomas: Role of the CXCL12/CXCR4-R7 System Mon, 17 Nov 2014 00:00:00 +0000 Chemokines are chemotactic regulators of immune surveillance in physiological and pathological conditions such as inflammation, infection, and cancer. Several chemokines and cognate receptors are constitutively expressed in the central nervous system, not only in glial and endothelial cells but also in neurons, controlling neurogenesis, neurite outgrowth, and axonal guidance during development. In particular, the chemokine CXCL12 and its receptors, CXCR4 and CXCR7, form a functional network that controls plasticity in different brain areas, influencing neurotransmission, neuromodulation, and cell migration, and the dysregulation of this chemokinergic axis is involved in several neurodegenerative, neuroinflammatory, and malignant diseases. CXCR4 primarily mediates the transduction of proliferative signals, while CXCR7 seems to be mainly responsible for scavenging CXCL12. Importantly, the multiple intracellular signalling generated by CXCL12 interaction with its receptors influences hypothalamic modulation of neuroendocrine functions, although a direct modulation of pituitary functioning via autocrine/paracrine mechanisms was also reported. Both CXCL12 and CXCR4 are constitutively overexpressed in pituitary adenomas and their signalling induces cell survival and proliferation, as well as hormonal hypersecretion. In this review we focus on the physiological and pathological functions of immune-related cyto- and chemokines, mainly focusing on the CXCL12/CXCR4-7 axis, and their role in pituitary tumorigenesis. Accordingly, we discuss the potential targeting of CXCR4 as novel pharmacological approach for pituitary adenomas. Federica Barbieri, Stefano Thellung, Roberto Würth, Federico Gatto, Alessandro Corsaro, Valentina Villa, Mario Nizzari, Manuela Albertelli, Diego Ferone, and Tullio Florio Copyright © 2014 Federica Barbieri et al. All rights reserved. Free Triiodothyronine Concentrations Are Inversely Associated with Microalbuminuria Sun, 16 Nov 2014 13:23:06 +0000 Thyroid function and microalbuminuria are both associated with vascular disease and endothelial damage. However, whether thyroid function is associated with microalbuminuria is not well established. The objective was to explore the relationship between thyroid hormones and microalbuminuria in Chinese population. A community-based cross-sectional study was performed among 3,346 Chinese adults (aged ≥ 40 years). Serum free triiodothyronine (FT3), free thyroxine (FT4), and TSH (thyroid stimulating hormone) were determined by chemiluminescent microparticle immunoassay. A single-void first morning urine sample was obtained for urinary albumin-creatinine ratio measurement. The prevalence of microalbuminuria decreased according to FT3 quartiles (13.2, 9.5, 8.6, and 8.2%, P for trend = 0.0005). A fully adjusted logistic regression analysis showed that high FT3 levels were associated with low prevalent microalbuminuria. The adjusted odds ratios for microalbuminuria were 0.61 (95% CI, 0.43–0.87, P = 0.007) when comparing the highest with the lowest quartile of FT3. The exclusion of participants with abnormal FT3 did not appreciably change the results (OR = 0.69, 95% CI, 0.49–0.98, P = 0.02). We concluded that serum FT3 levels, even within the normal range, were inversely associated with microalbuminuria in middle-aged and elderly Chinese adults. FT3 concentrations might play a role in the pathogenesis of microalbuminuria. Yulin Zhou, Lei Ye, Tiange Wang, Jie Hong, Yufang Bi, Jie Zhang, Baihui Xu, Jichao Sun, Xiaolin Huang, and Min Xu Copyright © 2014 Yulin Zhou et al. All rights reserved. Ethynilestradiol 20 mcg plus Levonorgestrel 100 mcg: Clinical Pharmacology Sun, 16 Nov 2014 00:00:00 +0000 Estroprogestins (EPs) are combinations of estrogen and progestin with several actions on women’s health. The different pharmacological composition of EPs is responsible for different clinical effects. One of the most used low-dose EP associations is ethinylestradiol 20 mcg plus levonorgestrel 100 mcg in monophasic regimen (EE20/LNG100). This review summarizes clinical pharmacology, cycle control, and effects on lipid and glucose metabolism, coagulation, body weight/body composition, acne, and sexuality of EE20/LNG100. Overall, EE20/LNG100 combination is safe and well tolerated, and in several studies the incidence of adverse events in the treated group was comparable to that of the placebo group. Cycle control was effective and body weight/body composition did not vary among treated and untreated groups in most studies. The EE20/LNG100 combination shows mild or no effect on lipid and glucose metabolism. Lastly, EE20/LNG100 is associated with a low risk of venous thromboembolism (VTE). In conclusion, in the process of decision making for the individualization of EPs choice, EE20/LNG100 should be considered for its favorable clinical profile. Stefano Lello and Andrea Cavani Copyright © 2014 Stefano Lello and Andrea Cavani. All rights reserved. Evaluating the Effect of Ramadan Fasting on Muslim Patients with Diabetes in relation to Use of Medication and Lifestyle Patterns: A Prospective Study Tue, 11 Nov 2014 11:47:07 +0000 Objectives. This study aimed to examine the effect of Ramadan fasting on HbA1c in Muslim patients with type 2 diabetes. The incidence of hypoglycemia and glycemic changes in relation to the adjustment of doses of antidiabetic agents, diet, and physical activity during Ramadan was also evaluated. Methods. This was a prospective study conducted in an outpatient endocrine clinic. A set of questionnaires was administered to Muslim patients with diabetes who fasted for 10 days. Those who were hospitalized for diabetic ketoacidosis or severe hypoglycemia a month prior to Ramadan or were given short-term corticosteroid therapy were excluded. The patients’ responses and clinical outcomes from the clinic database were collected before, during, and after Ramadan. Results. A total of 153 participants completed the study. The mean HbA1c improved from 8.9% before Ramadan to 8.6% during Ramadan (). Although diet and physical activity did not contribute to changes in glycemia, a significant improvement in HbA1c was observed in patients who had adjustments made to their doses of antidiabetic agents during Ramadan (). In addition, their rate of hypoglycemia was minimal. Conclusions. Ramadan fasting appeared to improve glycemic control, especially in those whose doses of antidiabetic agents were adjusted during Ramadan. Melanie Yee Lee Siaw, Daniel Ek Kwang Chew, Rinkoo Dalan, Shaikh Abdul Kader Kamaldeen Abdul Shakoor, Noorani Othman, Chor Hui Choo, Nur Hidayah Shamsuri, Siti Nurhana Abdul Karim, Sui Yung Chan, and Joyce Yu-Chia Lee Copyright © 2014 Melanie Yee Lee Siaw et al. All rights reserved. Determinants of Vitamin D Levels in Italian Children and Adolescents: A Longitudinal Evaluation of Cholecalciferol Supplementation versus the Improvement of Factors Influencing 25(OH)D Status Tue, 11 Nov 2014 07:52:27 +0000 Objective. This paper aims to assess 25(OH)D levels in Italian children and adolescents identifying risk factors for 25(OH)D deficiency and to evaluate whether a normal 25(OH)D value can be restored in 25(OH)D-deficient patients. Methods. We evaluated 25(OH)D levels in 679 Italian children and adolescents (≤10, 11–20, 21–30, and >30 ng/mL were defined as severe deficiency, deficiency, insufficiency, and sufficiency, resp.). Of these, 365 25(OH)D-deficient were followed up for 1 year; 205 were treated with cholecalciferol (Arm A: 400 I.U.) and 160 by improving the environmental variables influencing 25(OH)D levels (Arm B). Results. At cross-sectional evaluation, 11.3% showed sufficiency, 30.0% insufficiency, and 58.7% 25(OH)D deficiency. Mean 25(OH)D was  ng/mL. At the enrollment time (), no difference was found between Arms A and B with respect to distribution and 25(OH)D levels. At end time () 26.0% (29.7% in Arm A versus 20.6% in Arm B) showed sufficiency, 38.4% (42.0% versus 34.4%) insufficiency, and 35.6% (28.3% versus 45.0%) 25(OH)D deficiency. Mean 25(OH)D level was  ng/mL. Conclusions. Neither changes of lifestyle nor 400 I.U. cholecalciferol supplementation alone appears to be sufficient to restore adequate 25(OH)D levels. Stefano Stagi, Paola Pelosi, Massimo Strano, Giovanni Poggi, Cristina Manoni, Maurizio de Martino, and Salvatore Seminara Copyright © 2014 Stefano Stagi et al. All rights reserved. The Protective Effect of Beraprost Sodium on Diabetic Cardiomyopathy through the Inhibition of the p38 MAPK Signaling Pathway in High-Fat-Induced SD Rats Tue, 11 Nov 2014 00:00:00 +0000 Objective. To investigate the effect of beraprost sodium (BPS) on diabetic cardiomyopathy and the underlying mechanism. Methods. A total of 40 Sprague Dawley rats were randomly divided into the normal control group () and the model group (). The model group was fed a high-fat diet followed by a one-time dose of streptozotocin (STZ) to establish the diabetes mellitus model. After that, rats were randomly divided into two groups with or without BPS intervention. After 8 weeks, we explored the role of the p38 MAPK signaling pathway in inflammation, oxidative stress, cardiac morphology, and myocardial apoptosis. Results. Compared with control, the ratio of heart-weight to body-weight and the serum levels of SOD and GSH in the BPS group significantly increased, the expression of p38 MAPK, the serum levels of MDA, TGF-β1, TNF-α, HIF-1α, MMP-9, caspase-3, BNP, ANP, and heart Bax expression significantly decreased, and heart Bcl-2 expression significantly increased. H&E staining in diabetic rats showed the cardiac muscle fibers derangement, the widening gap, the pyknotic and fragmented nuclei, and more apoptosis. Conclusions. BPS effectively showed protective effects on diabetic myocardial cells, possibly through the inhibition of p38 MAPK signaling pathway. Jie Li, Li Peng, Hong Du, Yangtian Wang, Bin Lu, Yixin Xu, Xiaozhen Ye, and Jiaqing Shao Copyright © 2014 Jie Li et al. All rights reserved. Erratum to “Growth Retardation in Children with Kidney Disease” Mon, 10 Nov 2014 11:29:55 +0000 Paulina Salas, Viola Pinto, Josefina Rodriguez, Maria Jose Zambrano, and Veronica Mericq Copyright © 2014 Paulina Salas et al. All rights reserved. Correlations of Vascular Architecture and Angiogenesis with Pituitary Adenoma Histotype Sun, 09 Nov 2014 12:22:37 +0000 Vascular endothelial growth factor (VEGF) is a potent angiogenic factor in solid tumors. However, its role in angiogenesis in pituitary adenoma is controversial. Angiogenesis in solid tumors including pituitary adenoma is commonly evaluated by microvascular density (MVD). Here, we evaluated MVD and the role of VEGF in vascular architecture in 51 pituitary adenomas (24 nonfunctioning, 13 prolactin-secreting, 10 growth hormone-secreting, 3 adrenocorticotropic hormone-secreting, and 1 thyroid-stimulating hormone-secreting). Paraffin sections were stained with CD34 and VEGF. MVD and vascular architecture parameters (vessel area, diameter, perimeter, and roundness) were evaluated in CD34-stained sections. Immunohistochemistry showed 27/51 tumors (53%) were VEGF-positive. There were no significant differences in MVD, any vascular parameter, or adenoma volume between VEGF-positive and VEGF-negative tumors. VEGF mRNA expression was significantly higher in VEGF-positive tumors. There were no significant correlations between VEGF mRNA expression and MVD or vascular parameters. However, vessel diameter and perimeter were significantly larger in prolactin-secreting than nonfunctioning and growth hormone-secreting macroadenomas. The difference in vessel diameter was observed among both VEGF-positive and all adenomas (micro- and macroadenoma). Thus, VEGF may have limited roles in the development of vascular architecture and tumor angiogenesis in pituitary adenomas, but the differences in vessel architecture by histotype (i.e., larger vessel diameter and perimeter in prolactin-secreting adenomas) suggest the hormonal regulation of vessel architecture rather than angiogenesis Shingo Takano, Hiroyoshi Akutsu, Takuma Hara, Tetsuya Yamamoto, and Akira Matsumura Copyright © 2014 Shingo Takano et al. All rights reserved. Enucleation-Induced Rat Adrenal Gland Regeneration: Expression Profile of Selected Genes Involved in Control of Adrenocortical Cell Proliferation Thu, 06 Nov 2014 12:45:08 +0000 Enucleation-induced adrenal regeneration is a highly controlled process; however, only some elements involved in this process have been recognized. Therefore, we performed studies on regenerating rat adrenals. Microarray RNA analysis and QPCR revealed that enucleation resulted in a rapid elevation of expression of genes involved in response to wounding, defense response, and in immunological processes. Factors encoded by these genes obscure possible priming effects of various cytokines on initiation of regeneration. In regenerating adrenals we identified over 100 up- or downregulated genes involved in adrenocortical cell proliferation. The changes were most significant at days 2-3 after enucleation and their number decreased during regeneration. For example, expression analysis revealed a notable upregulation of the growth arrest gene, Gadd45, only 24 hours after surgery while expression of cyclin B1 and Cdk1 genes was notably elevated between days 1–8 of regeneration. These changes were accompanied by changes in expression levels of numerous growth factors and immediate-early transcription factors genes. Despite notable differences in mechanisms of adrenal and liver regeneration, in regenerating adrenals we identified genes, the expression of which is well recognized in regenerating liver. Thus, it seems legitimate to suggest that, in the rat, the general model of liver and adrenal regeneration demonstrate some degree of similarity. Marianna Tyczewska, Marcin Rucinski, Agnieszka Ziolkowska, Marta Szyszka, Marcin Trejter, Anna Hochol-Molenda, Krzysztof W. Nowak, and Ludwik K. Malendowicz Copyright © 2014 Marianna Tyczewska et al. All rights reserved. The Association between the Epicardial Adipose Tissue Thickness and Oxidative Stress Parameters in Isolated Metabolic Syndrome Patients: A Multimarker Approach Sun, 02 Nov 2014 14:28:34 +0000 The risk for cardiovascular diseases and type 2 diabetes mellitus significantly increases in the patient population with metabolic syndrome (MeS). The present study aimed to investigate the association between the epicardial adipose tissue thickness (EATT) and the oxidative stress parameters in MeS patients. The study included 181 patients as a patient group of 92 consecutive patients with MeS and a control group of 89 consecutive patients with similar age and gender. EATT was evaluated by transthoracic echocardiography. Serum levels of total oxidant status (TOS), total antioxidative capacity (TAS), paraoxonase-1 (PON-1), and arylesterase activities were measured. EATT was higher in the MeS group compared to the control group ( mm and  mm, resp.; ). The level of TOS was higher in the MeS group compared to the control group (). Additionally, the TAS level was higher in the MeS group compared to the control group (). Furthermore, the serum levels of PON-1 and arylesterase were lower in the MeS group compared to the control group (). EAT may cause an increased risk of cardiovascular diseases by leading to increased oxidative stress in patients with MeS. Bulent Demir, Esra Demir, Gonul Acıksarı, Turgut Uygun, Irem Kırac Utku, Asuman Gedikbasi, Ilker Murat Caglar, Osman Pirhan, Hande Oktay Tureli, Ersan Oflar, İsmail Ungan, Serkan Ciftci, and Osman Karakaya Copyright © 2014 Bulent Demir et al. All rights reserved. Erratum to “Influence of Vitamin D Binding Protein on Accuracy of 25-Hydroxyvitamin D Measurement Using the ADVIA Centaur Vitamin D Total Assay” Thu, 30 Oct 2014 06:56:13 +0000 James Freeman, Kimberly Wilson, Ryan Spears, Victoria Shalhoub, and Paul Sibley Copyright © 2014 James Freeman et al. All rights reserved. Alpha Lipoic Acid Modulated High Glucose-Induced Rat Mesangial Cell Dysfunction via mTOR/p70S6K/4E-BP1 Pathway Thu, 30 Oct 2014 00:00:00 +0000 The aim of this study was to investigate whether alpha lipoic acid (LA) regulates high glucose-induced mesangial cell proliferation and extracellular matrix production via mTOR/p70S6K/4E-BP1 signaling. The effect of LA on high glucose-induced cell proliferation, fibronectin (FN), and collagen type I (collagen-I) expression and its mechanisms were examined in cultured rat mesangial cells by methylthiazol tetrazolium (MTT) assay, flow cytometry, ELISA assay, and western blot, respectively. LA at a relatively low concentration (0.25 mmol/L) acted as a growth factor in rat mesangial cells, promoted entry of cell cycle into S phase, extracellular matrix formation, and phosphorylated AKT, mTOR, p70S6K, and 4E-BP1. These effects disappeared when AKT expression was downregulated with PI3K/AKT inhibitor LY294002. Conversely, LA at a higher concentration (1.0 mmol/L) inhibited high glucose-induced rat mesangial cell proliferation, entry of cell cycle into S phase, and extracellular matrix exertion, as well as phosphorylation of mTOR, p70S6K, and 4E-BP1 but enhanced the activity of AMPK. However, these effects disappeared when AMPK activity was inhibited with CaMKK inhibitor STO-609. These results suggest that LA dose-dependently regulates mesangial cell proliferation and matrix protein secretion by mTOR/p70S6K/4E-BP1 signaling pathway under high glucose conditions. Chuan Lv, Can Wu, Yue-hong Zhou, Ying Shao, Guan Wang, and Qiu-yue Wang Copyright © 2014 Chuan Lv et al. All rights reserved. Effect of High-Fat Diet on Peripheral Neuropathy in C57BL/6 Mice Mon, 27 Oct 2014 08:45:28 +0000 Objective. Dyslipidemia may contribute to the development of peripheral neuropathy, even in prediabetics; however, few studies have evaluated vascular dysfunction and oxidative stress in patients with peripheral neuropathy. Methods. Using high-fat diet- (HFD-) induced prediabetic C57BL/6 mice, we assessed motor and sensory nerve conduction velocity (NCV) using a BIOPAC System and thermal algesia with a Plantar Test (Hargreaves’ method) Analgesia Meter. Intraepidermal nerve fiber density and mean dendrite length were tested following standard protocols. Vascular endothelial growth factor-A (VEGF-A) and 12/15-lipoxygenase (12/15-LOX) were evaluated by immunohistochemistry and Western blot, respectively. Results. HFD-fed mice showed deficits in motor and sensory NCV, thermal hyperalgesia, reduced mean dendrite length, and VEGF-A expression in the plantar skin and increased 12/15-LOX in the sciatic nerve ( compared with controls). Conclusion. HFD may cause large myelinated nerve and small sensory nerve fiber damage, thus leading to neuropathy. The mean dendrite length may be a more sensitive marker for early detection of peripheral neuropathy. Reduced blood supply to the nerves and increased oxidative stress may contribute to the development and severity of peripheral neuropathy. Lingling Xu, Dou Tang, Meiping Guan, Cuihua Xie, and Yaoming Xue Copyright © 2014 Lingling Xu et al. All rights reserved. The Effects of Lycopene on the Methylation of the GSTP1 Promoter and Global Methylation in Prostatic Cancer Cell Lines PC3 and LNCaP Mon, 20 Oct 2014 06:59:41 +0000 DNA (cytosine-5-) methylation silencing of GSTP1 function occurs in prostate adenocarcinoma (PCa). Previous studies have shown that there is an inverse relationship between dietary lycopene intake and the risk of PCa. However, it is unknown whether lycopene reactivates the tumor suppressor gene glutathioneS-transferase-π (GSTP1) by demethylation of the hypermethylated CpGs that act to silence the GSTP1 promoter. Here, we demonstrated that lycopene treatment significantly decreased the methylation levels of the GSTP1 promoter and increased the mRNA and protein levels of GSTP1 in an androgen-independent PC-3 cell line. In contrast, lycopene treatment did not demethylate the GSTP1 promoter or increase GSTP1 expression in the androgen-dependent LNCaP cell line. DNA methyltransferase (DNMT) 3A protein levels were downregulated in PC-3 cells following lycopene treatment; however, DNMT1 and DNMT3B levels were unchanged. Furthermore, the long interspersed element (LINE-1) and short interspersed element ALU were not demethylated when treated by lycopene. In LNCaP cells, lycopene treatment did not affect any detected DNMT protein expression, and the methylation levels of LINE-1 and ALU were decreased. These results indicated that the protective effect of lycopene on the prostate is different between androgen-dependent and androgen-independent derived PCa cells. Further, in vivo studies should be conducted to confirm these promising results and to evaluate the potential role of lycopene in the protection of the prostate. Li-Juan Fu, Yu-Bin Ding, Lan-Xiang Wu, Chun-Jie Wen, Qiang Qu, Xue Zhang, and Hong-Hao Zhou Copyright © 2014 Li-Juan Fu et al. All rights reserved. Association of ATM Gene Polymorphism with PTC Metastasis in Female Patients Thu, 16 Oct 2014 13:02:01 +0000 Ataxia telangiectasia mutated (ATM) gene is critical in the process of recognizing and repairing DNA lesions and is related to invasion and metastasis of malignancy. The incidence rate of papillary thyroid cancer (PTC) has increased for several decades and is higher in females than males. In this study, we want to investigate whether ATM polymorphisms are associated with gender-specific metastasis of PTC. 358 PTC patients in Northern China, including 109 males and 249 females, were included in our study. Four ATM single nucleotide polymorphisms (SNPs) were genotyped using Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF-MS). Association between genotypes and the gender-specific risk of metastasis was assessed by odds ratios (OR) and 95% confidence intervals (CI) under the unconditional logistic regression analysis. Significant associations were observed between rs189037 and metastasis of PTC in females under different models of inheritance (codominant model: , 95% CI 0.04–0.56, for GA versus GG and , 95% CI 0.01–0.74, for AA versus GG, resp.; dominant model: , 95% CI 0.25–0.98, ; overdominant model: , 95% CI 0.25–0.89, ). However, no association remained significant after Bonferroni correction. Our findings suggest a possible association between ATM rs189037 polymorphisms and metastasis in female PTCs. Yulu Gu, Xiaoli Liu, Yaqin Yu, Jieping Shi, Lizhe Ai, Hui Sun, Joseph Sam Kanu, Chong Wang, and Yawen Liu Copyright © 2014 Yulu Gu et al. All rights reserved. Pretransplant HbA1c Is a Useful Predictor for the Development of New-Onset Diabetes in Renal Transplant Recipients Receiving No or Low-Dose Erythropoietin Thu, 16 Oct 2014 11:40:49 +0000 Aims. To evaluate the predictive power of pretransplant HbA1c for new-onset diabetes after transplantation (NODAT) in kidney transplant candidates, who had several predispositions for fluctuated HbA1c levels. Methods. We performed a retrospective study of 119 patients without diabetes who received kidney transplantation between March 2000 and January 2012. Univariate and multivariate logistic regression analyses were used to investigate the association of several parameters with NODAT. Predictive discrimination of HbA1c was assessed using a receiver-operating characteristic curve. Results. Seventeen patients (14.3%) developed NODAT within 1 year of transplantation. Univariate logistic regression analysis revealed that recipient age, gender, and HbA1c were predictors of NODAT. In the multivariate analysis, the association between pretransplant HbA1c and NODAT development did not reach statistical significance (). To avoid the strong influence of high-dose erythropoietin on HbA1c levels, we performed subgroup analyses on 85 patients receiving no or low-dose (≤6000 IU/week) erythropoietin. HbA1c was again an independent predictor for NODAT. Receiver-operating characteristic analysis revealed a cut-off value of 5.2% with an optimal sensitivity of 64% and specificity of 78% for predicting NODAT. Conclusions. Our results reveal that the pretransplant HbA1c level is a useful predictor for NODAT in patients receiving no or low-dose erythropoietin. Kazuaki Tokodai, Noritoshi Amada, Izumi Haga, Atsushi Nakamura, Toshiaki Kashiwadate, Naoki Kawagishi, and Noriaki Ohuchi Copyright © 2014 Kazuaki Tokodai et al. All rights reserved. Imaging-Cytology Correlation of Thyroid Nodules with Initially Benign Cytology Mon, 13 Oct 2014 12:51:16 +0000 Objective. To determine the role of imaging-cytology correlation in reducing false negative results of fine-needle aspiration (FNA) at thyroid nodules. Methods. This retrospective study included 667 nodules 1 cm or larger in 649 patients diagnosed as benign at initial cytologic evaluation and that underwent follow-up ultrasound (US) or FNA following a radiologist’s opinion on concordance between imaging and cytologic results. We compared the risk of malignancy of nodules classified into subgroups according to the initial US features and imaging-cytology correlation. Results. Among included nodules, 11 nodules were proven to be malignant (1.6%) in follow-up FNA or surgery. The malignancy rate was higher in nodules with suspicious US features (11.4%) than in nodules without suspicious US features (0.5%, ). When a thyroid nodule had discordant US findings on image review after having benign FNA results, malignancy rate increased to 23.3%, significantly higher than that of nodules with suspicious US features (). However, no significant difference was found in the risk of malignancy between the nodules without suspicious US features (0.5%) and imaging-cytology concordant nodules (0.6%, ). Conclusions. Repeat FNA can be effectively limited to patients with cytologically benign thyroid nodules showing discordance in imaging-cytology correlation after initial biopsy, which reduces unnecessary repeat aspirations. Shin Hye Hwang, Ji Min Sung, Eun-Kyung Kim, Hee Jung Moon, and Jin Young Kwak Copyright © 2014 Shin Hye Hwang et al. All rights reserved. Current Iodine Nutrition Status and Awareness of Iodine Deficiency in Tuguegarao, Philippines Mon, 13 Oct 2014 10:07:56 +0000 The Philippines is one of the countries where adequate iodine status has been achieved. However, iodine deficiency still remains an important public health problem in this country. In this study, we evaluated iodine nutrition status and investigated an awareness status of iodine deficiency targeting high school students of Tuguegarao, Philippines. A total of 260 students provided samples for urinary iodine analysis, among which 146 students completed thyroid volume measurement by ultrasonography and answering the questionnaires. The median urinary iodine level was 355.3 µg/L and only 3.8% of the students were in the range of iodine deficiency status according to the ICCIDD criteria. Although 62.3% of students answered that they can list problems resulting from iodine deficiency, a majority of students (70.5%) were unable to identify problems other than goiter. They did not appreciate that adequate iodine levels are important during pregnancy and for development of children. 33.6% of students answered that they did not use iodized salt and the biggest reason was that they did not find it necessary. Based on these results, we suggest that a future strategy should be focused on vulnerable groups to completely eliminate iodine deficiency, including women at their reproductive ages and during pregnancy. Bu Kyung Kim, Jee-Yeong Jeong, Kwang-Hyuk Seok, Andrew S. Lee, Chul Ho Oak, Ghi Chan Kim, Chae-Kyeong Jeong, Sung In Choi, Pablo M. Afidchao, and Young Sik Choi Copyright © 2014 Bu Kyung Kim et al. All rights reserved. Changes in Coagulation and Fibrinolytic Indices in Women with Polycystic Ovarian Syndrome Undergoing Controlled Ovarian Hyperstimulation Mon, 13 Oct 2014 08:38:15 +0000 Background. Polycystic ovarian syndrome (PCOS) women undergoing in vitro fertilization and embryo transfer (IVF-ET) treatment always attain a low cumulative pregnancy rate disaccording with the satisfactory number of oocytes. Objective. We aim to evaluate the status of coagulation and fibrinolytic system in PCOS patients undergoing controlled ovarian hyperstimulation (COH) process. Method. Of the 97 women, 30 patients with PCOS composed the study group; 67 women of child-bearing age with normal endocrine function composed the control group. All participants underwent GnRH agonist standard long protocol, and plasma HCY, FVIII, FX, and D-dimer levels as well as hormone parameters were measured at day of full downregulation, hCG priming, and embryos transfer. Results. On day of full downregulation, FX levels were significantly higher in PCOS group (). On hCG priming day, FX and estrogen levels in PCOS group were higher than in the control group and FVIII levels were significantly lower on day of embryos transfer whereas FX and E2 levels were significantly higher in PCOS group. Conclusion. Hypercoagulable state during peri-implantation phase would probably lead to poor microcirculation of endometrium and be one of the most important disadvantages of successful implantation and subsequent clinical pregnancy. Ying Huang, Yong Zhao, Ling Yan, Yun-Hai Chuai, Ling-Ling Liu, Yi Chen, Min Li, and Ai-Ming Wang Copyright © 2014 Ying Huang et al. All rights reserved. Autoimmune and Neoplastic Thyroid Diseases Associated with Hepatitis C Chronic Infection Mon, 13 Oct 2014 07:33:23 +0000 Frequently, patients with hepatitis C virus (HCV) chronic infection have high levels of serum anti-thyroperoxidase and/or anti-thyroglobulin autoantibodies, ultrasonographic signs of chronic autoimmune thyroiditis, and subclinical hypothyroidism, in female gender versus healthy controls, or hepatitis B virus infected patients. In patients with “HCV-associated mixed cryoglobulinemia” (MC + HCV), a higher prevalence of thyroid autoimmune disorders was shown not only compared to controls, but also versus HCV patients without cryoglobulinemia. Patients with MC + HCV or HCV chronic infection show a higher prevalence of papillary thyroid cancer than controls, in particular in patients with autoimmune thyroiditis. Patients with HCV chronic infection, or with MC + HCV, in presence of autoimmune thyroiditis, show higher serum levels of T-helper (Th)1 (C-X-C motif) ligand 10 (CXCL10) chemokine, but normal levels of Th2 (C-C motif) ligand 2 chemokine, than patients without thyroiditis. HCV thyroid infection could act by upregulating CXCL10 gene expression and secretion in thyrocytes recruiting Th1 lymphocytes that secrete interferon-γ and tumor necrosis factor-α. These cytokines might induce a further CXCL10 secretion by thyrocytes, thus perpetuating the immune cascade, which may lead to the appearance of autoimmune thyroid disorders in genetically predisposed subjects. A careful monitoring of thyroid function, particularly where nodules occur, is recommended in HCV patients. Poupak Fallahi, Silvia Martina Ferrari, Ugo Politti, Dilia Giuggioli, Clodoveo Ferri, and Alessandro Antonelli Copyright © 2014 Poupak Fallahi et al. All rights reserved. Correlation of High-Molecular-Weight Adiponectin and Leptin Concentrations with Anthropometric Parameters and Insulin Sensitivity in Newborns Sun, 12 Oct 2014 08:50:39 +0000 Objective. High-molecular-weight adiponectin (HMW-adiponectin) and leptin are two important adipokines. The aim of this study was to examine the association between the two adipokines and anthropometric measurements of neonates at birth. Furthermore, we would like to explore whether HMW-adiponectin and leptin correlate with insulin sensitivity in neonates. Methods. Venous cord blood samples were obtained from 266 full-term healthy neonates consecutively born at Peking Union Medical College Hospital. HMW-adiponectin, leptin, blood glucose, and insulin concentrations were measured. Results. HMW-adiponectin and leptin were significantly higher in females compared with males ( and , resp.). Univariate correlation analysis showed that leptin concentrations in cord blood were positively associated with gestational age, birth weight, body length, ponderal index, placenta weight, insulin, and insulin sensitivity (all ). However, there was no correlation between cord blood HMW-adiponectin levels and foetal anthropometric measurements or foetal insulin sensitivity indicators (all ). Multivariate linear regression analysis indicated that leptin (, ) in cord blood was independently associated with insulin sensitivity. Conclusions. Leptin concentrations, but not HMW-adiponectin, were positively associated with foetal anthropometric measurements. Leptin concentrations are significantly associated with foetal insulin sensitivity, and there were no significant correlations between HMW-adiponectin levels and foetal insulin sensitivity. Jia Zheng, Xinhua Xiao, Qian Zhang, Lili Mao, Ming Li, Miao Yu, Jianping Xu, and Ying Wang Copyright © 2014 Jia Zheng et al. All rights reserved. Genetic Variations in the Kir6.2 Subunit (KCNJ11) of Pancreatic ATP-Sensitive Potassium Channel Gene Are Associated with Insulin Response to Glucose Loading and Early Onset of Type 2 Diabetes in Childhood and Adolescence in Taiwan Sun, 21 Sep 2014 09:31:58 +0000 To investigate the role of E23K polymorphism of the KCNJ11 gene on early onset of type 2 diabetes in school-aged children/adolescents in Taiwan, we recruited 38 subjects with type 2 diabetes (ages 18.6 ± 6.6 years; body mass index percentiles 83.3 ± 15.4) and 69 normal controls (ages 17.3 ± 3.8 years; body mass index percentiles 56.7 ± 29.0) from a national surveillance for childhood/adolescent diabetes in Taiwan. We searched for the E23K polymorphism of the KCNJ11 gene. We found that type 2 diabetic subjects had higher carrier rate of E23K polymorphism of KCNJ11 gene than control subjects (P = 0.044). After adjusting for age, gender, body mass index percentiles, and fasting plasma insulin, the E23K polymorphism contributed to an increased risk for type 2 diabetes (P = 0.047). K23-allele-containing genotypes conferring increased plasma insulin level during OGTT in normal subjects. However, the diabetic subjects with the K23-allele-containing genotypes had lower fasting plasma insulin levels after adjustment of age and BMI percentiles. In conclusion, the E23K variant of the KCNJ11 gene conferred higher susceptibility to type 2 diabetes in children/adolescents. Furthermore, in normal glucose-tolerant children/adolescents, K23 allele carriers had a higher insulin response to oral glucose loading. Yi-Der Jiang, Lee-Ming Chuang, Dee Pei, Yann-Jinn Lee, Jun-Nan Wei, Fung-Chang Sung, and Tien-Jyun Chang Copyright © 2014 Yi-Der Jiang et al. All rights reserved. Differences in the Cardiometabolic Control in Type 2 Diabetes according to Gender and the Presence of Cardiovascular Disease: Results from the eControl Study Sun, 21 Sep 2014 05:40:40 +0000 The objective of this cross-sectional study was to assess differences in the control and treatment of modifiable cardiovascular risk factors (CVRF: HbA1c, blood pressure [BP], LDL-cholesterol, body mass index, and smoking habit) according to gender and the presence of cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM) in Catalonia, Spain. The study included available data from electronic medical records for a total of 286,791 patients. After controlling for sex, age, diabetes duration, and treatment received, both men and women with prior CVD had worse cardiometabolic control than patients without previous CVD; women with prior CVD had worse overall control of CVRFs than men except for smoking; and women without prior CVD were only better than men at controlling smoking and BP, with no significant differences in glycemic control. Finally, although the proportion of women treated with lipid-lowering medications was similar to (with prior CVD) or even higher (without CVD) than men, LDL-cholesterol levels were remarkably uncontrolled in both women with and women without CVD. The results stress the need to implement measures to better prevent and treat CVRF in the subgroup of diabetic women, specifically with more intensive statin treatment in those with CVD. Josep Franch-Nadal, Manel Mata-Cases, Irene Vinagre, Flor Patitucci, Eduard Hermosilla, Aina Casellas, Bonaventura Bolivar, and Dídac Mauricio Copyright © 2014 Josep Franch-Nadal et al. All rights reserved. Better Understanding in the Differentiation of Thyroid Follicular Adenoma, Follicular Carcinoma, and Follicular Variant of Papillary Carcinoma: A Retrospective Study Thu, 18 Sep 2014 07:43:40 +0000 Background. To evaluate the role of ultrasonography (US), US-guided fine-needle aspiration (USFNA) and intraoperative frozen section (FS) in follicular neoplasm. Methods. US features, USFNA cytology, and FS results were compared based on the pathology results of patients with follicular adenoma (FA), follicular carcinoma (FC), and follicular variant of papillary thyroid carcinoma (FVPTC). Results. FC and FVPTC showed significantly higher rates of suspicious US features () and positive findings on either US or cytology, 80.0% and 90.7%, compared to FA, 64.5% (). Intraoperative FS showed higher malignant rates in FVPTC and FC (81.8% and 75.0%, resp.), compared to FA (3.8%, ). Conclusion. Suspicious US features were more significantly seen in FC and FVPTC compared to FA. Intraoperative FS is useful in the differential diagnosis of these lesions and supplements cytology results of USFNA. Jung Hyun Yoon, Eun-Kyung Kim, Ji Hyun Youk, Hee Jung Moon, and Jin Young Kwak Copyright © 2014 Jung Hyun Yoon et al. All rights reserved. Augmented β-Cell Function and Mass in Glucocorticoid-Treated Rodents Are Associated with Increased Islet Ir-β/AKT/mTOR and Decreased AMPK/ACC and AS160 Signaling Wed, 17 Sep 2014 09:37:33 +0000 Glucocorticoid (GC) therapies may adversely cause insulin resistance (IR) that lead to a compensatory hyperinsulinemia due to insulin hypersecretion. The increased β-cell function is associated with increased insulin signaling that has the protein kinase B (AKT) substrate with 160 kDa (AS160) as an important downstream AKT effector. In muscle, both insulin and AMP-activated protein kinase (AMPK) signaling phosphorylate and inactivate AS160, which favors the glucose transporter (GLUT)-4 translocation to plasma membrane. Whether AS160 phosphorylation is modulated in islets from GC-treated subjects is unknown. For this, two animal models, Swiss mice and Wistar rats, were treated with dexamethasone (DEX) (1 mg/kg body weight) for 5 consecutive days. DEX treatment induced IR, hyperinsulinemia, and dyslipidemia in both species, but glucose intolerance and hyperglycemia only in rats. DEX treatment caused increased insulin secretion in response to glucose and augmented β-cell mass in both species that were associated with increased islet content and increased phosphorylation of the AS160 protein. Protein AKT phosphorylation, but not AMPK phosphorylation, was found significantly enhanced in islets from DEX-treated animals. We conclude that the augmented β-cell function developed in response to the GC-induced IR involves inhibition of the islet AS160 protein activity. André O. P. Protzek, José M. Costa-Júnior, Luiz F. Rezende, Gustavo J. Santos, Tiago Gomes Araújo, Jean F. Vettorazzi, Fernanda Ortis, Everardo M. Carneiro, Alex Rafacho, and Antonio C. Boschero Copyright © 2014 André O. P. Protzek et al. All rights reserved.