International Journal of Endocrinology The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Stability of miR-126 in Urine and Its Potential as a Biomarker for Renal Endothelial Injury with Diabetic Nephropathy Thu, 17 Apr 2014 16:48:53 +0000 Background. The purpose of the present study was to assess the feasibility of using miR-126 in the urine as a biomarker for diabetic nephropathy. Methods. miRNAs were extracted from the urine samples of T2DM patients with diabetic nephropathy (DN; ), T2DM without DN (), and 85 healthy volunteers using quantitative reverse transcriptase polymerase chain reaction (real-time polymerase chain reaction) analysis. Stability of urinary miR-126 and factors that affected the stability were assessed. A subgroup analysis was also carried out to compare the urinary miR-126 level in T2DM patients well controlled by the treatment versus those who were not well controlled. Results. Urinary miR-126 was stable when the urine samples were kept at room temperature for extended period of time, 4°C, −20°C, and −80°C for up to 12 hours or subjected to 10 freeze-and-thaw cycle. Urinary miR-126 was significantly higher in T2DM patients with DN ( versus in T2DM patients without DN). Successful treatment significantly reduced urinary miR-126 in T2DM patients with DN to (). Conclusion. miR-126 in the urine is stable and it could be used as a biomarker of DN and to monitor the treatment response. Yang Liu, Guangqiang Gao, Chun Yang, Kun Zhou, Baozhong Shen, Hongyan Liang, and Xiaofeng Jiang Copyright © 2014 Yang Liu et al. All rights reserved. Visceral Adiposity Index: An Indicator of Adipose Tissue Dysfunction Mon, 14 Apr 2014 14:14:31 +0000 The Visceral Adiposity Index (VAI) has recently proven to be an indicator of adipose distribution and function that indirectly expresses cardiometabolic risk. In addition, VAI has been proposed as a useful tool for early detection of a condition of cardiometabolic risk before it develops into an overt metabolic syndrome. The application of the VAI in particular populations of patients (women with polycystic ovary syndrome, patients with acromegaly, patients with NAFLD/NASH, patients with HCV hepatitis, patients with type 2 diabetes, and general population) has produced interesting results, which have led to the hypothesis that the VAI could be considered a marker of adipose tissue dysfunction. Unfortunately, in some cases, on the same patient population, there is conflicting evidence. We think that this could be mainly due to a lack of knowledge of the application limits of the index, on the part of various authors, and to having applied the VAI in non-Caucasian populations. Future prospective studies could certainly better define the possible usefulness of the VAI as a predictor of cardiometabolic risk. Marco Calogero Amato and Carla Giordano Copyright © 2014 Marco Calogero Amato and Carla Giordano. All rights reserved. Hip Osteoarthritis and Osteoporosis: Clinical and Histomorphometric Considerations Mon, 14 Apr 2014 11:38:41 +0000 Although an inverse relationship between osteoarthritis (OA) and osteoporosis (OP) has been shown by some studies, other reports supported their coexistence. To clarify this relationship, we analyzed the interplay between clinical and histomorphometric features. Bone mineral density (BMD) and histomorphometric structure were assessed in 80 patients of four different age-matched groups undergoing hip arthroplasty for severe OA or OP-related femoral fracture. Harris Hip Score was also performed. Surgical double osteotomy of the femoral head was performed and microscopic bone slice samples analysis was performed by using a BioQuant Osteo software. Bone volume fraction (BV/TV) was lower () in subjects with femoral neck fracture (%) than in subjects with nonosteopenic OA (%) or osteopenic OA (%), whereas no difference was detected between subjects with femoral neck fractures and those with combined OA and OP (%). Worse Harris Hip Score was found in those patients with the lowest BMD and BV/TV values. Our data support recent evidences indicating the possibility of impaired bone volume fraction in OA patients, with a high risk of developing OP, likely for their decreased mobility. Further studies are needed in order to investigate biomolecular pathway and/or growth factors involved in bone volume impairment in OA patients. Umberto Tarantino, Monica Celi, Cecilia Rao, Maurizio Feola, Irene Cerocchi, Elena Gasbarra, Amedeo Ferlosio, and Augusto Orlandi Copyright © 2014 Umberto Tarantino et al. All rights reserved. Coordinating Care Aspects Related to Sexual Health in the Aging Male Mon, 14 Apr 2014 11:23:51 +0000 Antonio Aversa, Lorenzo Maria Donini, Roberto Bruzziches, Roberto LaCava, Francesco Mattace Raso, and Alan Sinclair Copyright © 2014 Antonio Aversa et al. All rights reserved. Functional Analysis of Thyroid Peroxidase Gene Mutations Detected in Patients with Thyroid Dyshormonogenesis Sun, 13 Apr 2014 15:01:44 +0000 Thyroid peroxidase (TPO) is the key enzyme in the biosynthesis of thyroid hormones. We aimed to identify the spectrum of mutations in the TPO gene leading to hypothyroidism in the population of West Bengal to establish the genetic etiology of the disease. 200 hypothyroid patients (case) and their corresponding sex and age matched 200 normal individuals (control) were screened depending on their clinical manifestations. Genomic DNA was isolated from peripheral blood samples and TPO gene (Exon 7 to Exon 14) was amplified by PCR. The PCR products were subjected to sequencing to identify mutations. Single nucleotide changes such as Glu 641 Lys, Asp 668 Asn, Thr 725 Pro, Asp 620 Asn, Ser 398 Thr, and Ala 373 Ser were found. Changes in the TPO were assayed in vitro to compare mutant and wild-type activities. Five mutants were enzymatically inactive in the guaiacol and iodide assays. This is a strong indication that the mutations are present at crucial positions of the TPO gene, resulting in inactivated TPO. The results of this study may help to develop a genetic screening protocol for goiter and hypothyroidism in the population of West Bengal. Srikanta Guria, Biswabandhu Bankura, Nisha Balmiki, Arup Kumar Pattanayak, Tapas Kumar Das, Anirban Sinha, Sudipta Chakrabarti, Subhankar Chowdhury, and Madhusudan Das Copyright © 2014 Srikanta Guria et al. All rights reserved. Vitamin D Binding Protein Affects the Correlation of 25(OH)D and Frailty in the Older Men Sun, 13 Apr 2014 00:00:00 +0000 Vitamin D binding protein (DBP) may alter the biologic activity of 25-hydroxyvitamin D [25(OH)D]. The objective of our present study was to determine the joint effect of serum 25(OH)D and DBP on the risk of frailty. Five hundred sixteen male participants aged 70 years or older were recruited in Changsha city and its surrounding area in Hunan province of China. Frailty was defined as the presence of at least three of the five following criteria: weakness, low physical activity, slow walking speed, exhaustion, and weight loss. Multivariate linear regression analysis was performed to assess the relationship between 25(OH)D and DBP levels. Odds ratios (ORs) for frailty were evaluated across quartiles of 25(OH)D and DBP levels, adjusted age, education, and body mass index. The results showed that participants in the lowest quartile of 25(OH)D and the highest quartile of DBP levels, the lowest quartile of 25(OH)D and the lowest quartile of DBP levels, and those in the the lower quartile of 25(OH)D and lowest quartile of DBP levels had significantly higher OR of being frail compared with those in the highest quartile of 25(OH)D and lowest quartile of DBP, with OR of 3.18 (95% CI: 1.46–4.56, ), 2.63 (95% CI: 1.31–3.68, ), and 2.52 (95% CI: 1.22–3.52, ), respectively. The results indicate that the joint effect of serum 25(OH)D and DBP levels is associated with the risk of frailty, and serum DBP levels affects 25(OH)D-frailty relationship in the older men. Yi Wang, Yan-Jiao Wang, Jun-Kun Zhan, Zhi-Yong Tang, Wu Huang, Pan Tan, Shan Gao, Cai-Li Ma, Zai-Jin Jian, and You-Shuo Liu Copyright © 2014 Yi Wang et al. All rights reserved. Role of Serum Fibrinogen Levels in Patients with Rotator Cuff Tears Thu, 10 Apr 2014 12:13:25 +0000 Although rotator cuff (RC) tendinopathy is a frequent pathology of the shoulder, the real understanding of its aetiopathogenesis is still unclear. Several studies showed that RC tendinopathy is more frequent in patients with hyperglycemia, diabetes, obesity, or metabolic syndrome. This paper aims to evaluate the serum concentration of fibrinogen in patients with RC tears. Metabolic disorders have been related to high concentration of serum fibrinogen and the activity of fibrinogen has been proven to be crucial in the development of microvascular damage. Thus, it may produce progression of RC degeneration by reducing the vascular supply of tendons. We report the results of a cross-sectional frequency-matched case-control study comparing the serum concentration of fibrinogen of patients with RC tears with that of a control group of patients without history of RC tears who underwent arthroscopic meniscectomy. We choose to enrol in the control group patients with pathology of the lower limb with a likely mechanic, not metabolic, cause, different from tendon pathology. We found no statistically significant differences in serum concentration of fibrinogen when comparing patients with RC tears and patients who underwent arthroscopic meniscectomy (P = 0.5). Further studies are necessary to clarify the role of fibrinogen in RC disease. Umile Giuseppe Longo, Stefano Petrillo, Alessandra Berton, Filippo Spiezia, Mattia Loppini, Nicola Maffulli, and Vincenzo Denaro Copyright © 2014 Umile Giuseppe Longo et al. All rights reserved. Etiopathogenesis of Sheehan’s Syndrome: Roles of Coagulation Factors and TNF-Alpha Thu, 10 Apr 2014 11:45:17 +0000 Sheehan’s Syndrome (SS) is defined as pituitary hormone deficiency due to ischemic infarction of the pituitary gland as a result of massive postpartum uterine hemorrhage. Herein, we aimed to investigate the roles of Factor II (G20210A), Factor V (G1691A), MTHFR (C677T and A1298C), PAI-1 4G/5G, and TNF-α () gene polymorphisms in the etiopathogenesis of SS. Venous blood samples were obtained from 53 cases with SS and 43 healthy women. Standard methods were used to extract the genomic DNAs. Factor II (G20210A), Factor V (G1691A), and MTHFR (C677T and A1298C) polymorphisms were identified by real-time PCR. PAI-1 4G/5G and TNF-α () gene polymorphisms were detected with polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods. According to statistical analysis, none of the polymorphisms were found to be significantly higher in the SS group compared to the control group. Hence, we suggest that genetic factors other than Factor II, Factor V, MTHFR, PAI-1, and TNF-α gene polymorphisms should be researched in the etiopathogenesis of SS. Halit Diri, Elif Funda Sener, Fahri Bayram, Nazife Tascioglu, Yasin Simsek, and Munis Dundar Copyright © 2014 Halit Diri et al. All rights reserved. Adrenal Incidentalomas: Should We Operate on Small Tumors in the Era of Laparoscopy? Thu, 10 Apr 2014 09:14:12 +0000 Tumor size smaller than 4 cm as an indication for surgical treatment of incidentaloma is still a subject of discussion. Our aim was the estimation of the incidence of malignancy and analysis of treatment outcomes in patients with incidentaloma smaller than 4 cm in comparison to bigger lesions. 132 patients who underwent laparoscopic adrenalectomy for nonsecreting tumors were divided into two groups: group 1 (55 pts., size < = 40 mm) and group 2 (77 pts., size > 40 mm). Operation parameters and histopathological results were analyzed. No differences in group characteristics, mean operation time, and estimated blood loss were noted. Complications in groups 1 and 2 occurred in 3.6% and 5.2% of patients, respectively (). Malignancy in groups 1 and 2 was present in 1 and 6 patients, respectively (). Potentially malignant lesions were identified in 4 patients in group 1 and 4 patients in group 2 (). The results do not allow for straightforward recommendations for surgical treatment of smaller adrenal tumors. The safety of laparoscopy and minimal, but impossible to omit, risk of malignancy support decisions for surgery. On the other hand, the risk of malignancy in smaller adrenal tumors is lower than surgical complications, which provides an important argument against surgery. Michał Pędziwiatr, Michał Natkaniec, Mikhail Kisialeuski, Piotr Major, Maciej Matłok, Damian Kołodziej, Anna Zub-Pokrowiecka, Piotr Budzyński, and Andrzej Budzyński Copyright © 2014 Michał Pędziwiatr et al. All rights reserved. Efficacy and Safety of Sitagliptin for the Treatment of New-Onset Diabetes after Renal Transplantation Thu, 10 Apr 2014 08:34:29 +0000 New-onset diabetes after transplantation (NODAT) is a common comorbidity after renal transplantation. Though metformin is the first-line agent for the treatment of type 2 diabetes, in renal transplant recipients, metformin is frequently avoided due to concerns about renal dysfunction and risk for lactic acidosis. Therefore, alternative first-line agents for the treatment of NODAT in renal transplant recipients are needed. Sitagliptin, a dipeptidyl-peptidase-4 (DPP-4) inhibitor, has a low incidence of hypoglycemia, is weight neutral, and, in a small study, did not affect immunosuppressant levels. However, long-term sitagliptin use for the treatment of NODAT in kidney transplant recipients has not been studied. We retrospectively analyzed renal transplant recipients diagnosed with NODAT and treated with sitagliptin to assess safety and efficacy. Twenty-two patients were started on sitagliptin alone. After 12 months of followup, 19/22 patients remained on sitagliptin alone with a significant improvement in hemoglobin A1c. Renal function and immunosuppressant levels remained stable. Analysis of long-term followup (32.5 17.8 months) revealed that 17/22 patients remained on sitagliptin (mean hemoglobin A1c < 7%) with 9/17 patients remaining on sitagliptin alone. Transplant-specific adverse events were rare. Sitagliptin appears safe and efficacious for the treatment of NODAT in kidney transplant recipients. Brian P. Boerner, Clifford D. Miles, and Vijay Shivaswamy Copyright © 2014 Brian P. Boerner et al. All rights reserved. Testosterone Deficiency, Cardiac Health, and Older Men Thu, 10 Apr 2014 07:16:06 +0000 Low levels of testosterone are manifested by erectile dysfunction, reduced sexual desire, and loss of morning erections with increasing numbers of men are being diagnosed and require treatment. The prevalence rates of testosterone deficiency vary according to different studies but may be as high as 40% in populations of patients with type 2 diabetes. There is increasing evidence that testosterone deficiency is associated with increased cardiovascular and all-cause mortality. Screening for low testosterone is recommended in a number of high risk groups including those with type 2 diabetes and metabolic syndrome. There are recent data to suggest that testosterone replacement therapy may reduce cardiovascular mortality as well as improving multiple surrogate markers for cardiovascular events. Specific clinical trials of testosterone replacement therapy are needed in selected populations but in the meantime we must treat patients based on the best current evidence. G. Hackett, M. Kirby, and A. J. Sinclair Copyright © 2014 G. Hackett et al. All rights reserved. Repeat FNA Significantly Lowers Number of False Negative Results in Patients with Benign Nodular Thyroid Disease and Features of Chronic Thyroiditis Wed, 09 Apr 2014 09:11:19 +0000 Purpose. The aim of the study was to compare the risk of thyroid malignancy and efficacy of repeat FNA in patients with thyroid nodules diagnosed cytologically as benign lesion (BL) with features of chronic thyroiditis (BL-CT) and BL without CT features (BL-nCT). Methods. The analysis included 917 patients with BL-CT and 7046 with BL-nCT in the first FNA. Repeat biopsy was carried out in 787 patients of BL-CT and 5147 of BL-nCT; 218 patients of BL-CT and 2462 of BL-nCT were operated; in 88 cases of BL-CT and 563 of BL-nCT both ways of follow-up were available. Results. Outcome of repeat cytology implied surgery more frequently in patients with BL-CT than with BL-nCT—3.2% versus 1.9%, < 0.05. Incidence of cancer (including incidentalomas) was higher in patients with BL-CT operated after one benign cytology than in patients with two benign FNA outcomes: 10.8% versus 1.6%, < 0.05. In patients with BL-nCT that difference was not significant: 3.2% versus 2.6%. Conclusions. Patients with thyroid nodules diagnosed as BL with CT features have higher risk of malignancy than patients with BL without CT features. Repeat biopsy significantly lowers percentage of FN results in patients with BL-CT in the first FNA. Dorota Słowińska-Klencka, Ewa Woźniak-Oseła, Bożena Popowicz, Stanisław Sporny, and Mariusz Klencki Copyright © 2014 Dorota Słowińska-Klencka et al. All rights reserved. Acute One-Cigarette Smoking Decreases Ghrelin Hormone in Saliva: A Pilot Study Mon, 07 Apr 2014 13:58:15 +0000 Cigarette smoking is commonly associated with weight loss and mechanisms for these weight changes are still elusive. Ghrelin is a peptide hormone that works in a neuroendocrine fashion to stimulate hunger and the desire for food intake. Ghrelin is also secreted in saliva, probably to enhance food taste. In the current study, we tested the direct impact of acute cigarette smoking on total ghrelin found in saliva. Methods. Blood and saliva samples were collected from 30 healthy nonsmoker male volunteers before and after one-cigarette smoke. Total ghrelin in serum and saliva was measured by ELISA based method. Results. Data showed a statistically significant reduction in salivary ghrelin after smoking . In serum, total ghrelin levels were not affected before and after smoking . Additionally, positive correlation was observed between serum and salivary ghrelin before smoking and ; however, this correlation was lost after smoking and . Conclusion. Acute one-cigarette smoking can negatively affect ghrelin levels in saliva that might contribute to the dull food taste in smokers. Yahia A. Kaabi and Mohiealdeen A. Khalifa Copyright © 2014 Yahia A. Kaabi and Mohiealdeen A. Khalifa. All rights reserved. Diabetic Renal Disease Mon, 07 Apr 2014 09:34:29 +0000 Stephen Fava, Samy Hadjadj, and James Walker Copyright © 2014 Stephen Fava et al. All rights reserved. Bone and Mineral Metabolism in Patients with Primary Aldosteronism Thu, 03 Apr 2014 06:34:42 +0000 Primary aldosteronism represents major cause of secondary hypertension, strongly associated with high cardiovascular morbidity and mortality. Aldosterone excess may influence mineral homeostasis, through higher urinary calcium excretion inducing secondary increase of parathyroid hormone. Recently, in a cohort of PA patients a significant increase of primary hyperparathyroidism was found, suggesting a bidirectional functional link between the adrenal and parathyroid glands. The aim of this study was to evaluate the impact of aldosterone excess on mineral metabolism and bone mass density. In 73 PA patients we evaluated anthropometric and biochemical parameters, renin-angiotensin-aldosterone system, calcium-phosphorus metabolism, and bone mineral density; control groups were 73 essential hypertension (EH) subjects and 40 healthy subjects. Compared to HS and EH, PA subjects had significantly lower serum calcium levels and higher urinary calcium excretion. Moreover, PA patients showed higher plasma PTH, lower serum 25(OH)-vitamin D levels, higher prevalence of vitamin D deficiency (65% versus 25% and 25%; ), and higher prevalence of osteopenia/osteoporosis (38.5 and 10.5%) than EH (28% and 4%) and NS (25% and 5%), respectively. This study supports the hypothesis that bone loss and fracture risk in PA patients are potentially the result of aldosterone mediated hypercalciuria and the consecutive secondary hyperparathyroidism. Luigi Petramala, Laura Zinnamosca, Amina Settevendemmie, Cristiano Marinelli, Matteo Nardi, Antonio Concistrè, Francesco Corpaci, Gianfranco Tonnarini, Giorgio De Toma, and Claudio Letizia Copyright © 2014 Luigi Petramala et al. All rights reserved. Subacute Thyroiditis: Clinical Presentation and Long Term Outcome Thu, 03 Apr 2014 00:00:00 +0000 Few studies have been reported from the Kingdom of Saudi Arabia (SA) to describe the clinical presentation and long term outcomes of subacute thyroiditis (SAT). Our aim was to review the demographic, anthropometric, clinical presentation, laboratory results, treatment, and disease outcome in Riyadh region and to compare those with results from different regions of the Kingdom and different parts of the world. We reviewed the medical files of patients who underwent thyroid uptake scan during an 8-year period in King Khalid University Hospital. Only 25 patients had confirmed diagnosis of thyroiditis. Age and gender distribution were similar to other studies. Most patients presented with palpitation, goiter, and weight change. Elevated thyroid hormones, suppressed thyroid-stimulating hormone, and elevated ESR were reported. Among those, 7 cases of SAT were recorded. β-Blockers were prescribed to 57% and nonsteroidal anti-inflammatory drugs to 29% of SAT. Long follow-up demonstrated that 85.7% of SAT cases recovered, while 14.3% developed permanent hypothyroidism. In conclusion, SAT is uncommon in the central region of SA. Compared to the western region, corticosteroid is not commonly prescribed, and permanent hypothyroidism is not uncommon. A nation-wide epidemiological study to explain these interprovincial differences is warranted. Assim A. Alfadda, Reem M. Sallam, Ghadi E. Elawad, Hisham AlDhukair, and Mossaed M. Alyahya Copyright © 2014 Assim A. Alfadda et al. All rights reserved. Neuropeptides and Control of Food Intake Wed, 02 Apr 2014 12:57:15 +0000 Paolo de Girolamo and Carlos Dieguez Copyright © 2014 Paolo de Girolamo and Carlos Dieguez. All rights reserved. Behavioural Outcome in Children with Congenital Adrenal Hyperplasia: Experience of a Single Centre Tue, 01 Apr 2014 07:36:52 +0000 The aim of this study was to determine the behavioral outcome in children with CAH and to identify the risk factors that may influence it. Participants (aged 6–18 years) included 29 girls and 20 boys with CAH and unaffected siblings (25 girls and 17 boys). Psychological adjustment was assessed with parent reports on the Child Behavior Checklist (CBCL). Information about disease characteristics was obtained from medical records. Our study reveals that there was higher incidence of parent-reported problem of anxious/depressed and withdrawn/depressed behaviours, somatic complaints, social, thought, and attention problems, and rule-breaking, aggressive, internalizing, and externalizing behaviour among children with CAH compared to controls. The prevalence of internalizing behaviour problems was higher in CAH boys compared with that of controls. Psychosocial adjustment of girls with CAH was found to be similar to unaffected female controls and was within the normal population range. Family income may be associated with behavioral outcome. Glucocorticoid dose may reflect disease severity which may be associated with behavioral outcome. We conclude that internalizing behavioral problem was prevalent among boys with CAH reflecting maladaptive adjustment in coping with chronic illness. This highlighted the importance of psychological and social support for the patients and their families. Arini Nuran Idris, Viji Chandran, Syed Zulkifli Syed Zakaria, and Rahmah Rasat Copyright © 2014 Arini Nuran Idris et al. All rights reserved. Plasma Antimicrobial Peptide LL-37 Level Is Inversely Associated with HDL Cholesterol Level in Patients with Type 2 Diabetes Mellitus Wed, 26 Mar 2014 13:46:08 +0000 Introduction. Relation between atherosclerosis and innate immunity has attracted attention. As the antimicrobial peptide, LL-37, could have an important role in atherosclerosis, we supposed that there could be a meaningful association of plasma LL-37 level with risk factors for cardiovascular disease in subjects with type 2 diabetes mellitus. Materials and Methods. We evaluated plasma LL-37 level and other clinical markers in Japanese subjects with type 2 diabetes mellitus (, 115 men and 18 women; age years; HbA1c %). Plasma level of LL-37 was measured by ELISA. Results. Mean plasma LL-37 level was  ng/mL. Plasma LL-37 level showed significant correlations with HDL cholesterol (, ), triglyceride (, ), and high sensitive C-reactive protein (, ) but no significant correlation with age, body mass index, HbA1c, estimated glomerular filtration rate, 25-hydroxyvitamin D, or vitamin D binding protein. Multiple linear regression analysis showed significant correlations of plasma LL-37 level with HDL cholesterol (, ) and high sensitive C-reactive protein (, ). Conclusion. Plasma LL-37 level was positively correlated with inflammatory markers and negatively correlated with HDL cholesterol in patients with type 2 diabetes mellitus. Shu Meguro, Masuomi Tomita, Takeshi Katsuki, Kiyoe Kato, Henpiru Oh, Akira Ainai, Ryo Ito, Toshihide Kawai, Hiroshi Itoh, and Hideki Hasegawa Copyright © 2014 Shu Meguro et al. All rights reserved. Gene Expression Profiling of the Paracrine Effects of Uterine Natural Killer Cells on Human Endometrial Epithelial Cells Wed, 26 Mar 2014 12:44:14 +0000 The endometrium contains a population of immune cells that undergo changes during implantation and pregnancy. The majority of these cells are uterine natural killer (uNK) cells; however, it is unclear how these cells interact with endometrial epithelial cells. Therefore, we investigated the paracrine effects of the uNK cell-secretion medium on the gene expression profile of endometrial epithelial cells in vitro through microarray analysis. Our results, which were verified by qRT-PCR and western blot, revealed that soluble factors from uNK cells alter the gene expression profiles of epithelial cells. The upregulated genes included interleukin-15 (IL-15) and interleukin-15 receptor alpha (IL-15RA), which result in a loop that stimulates uNK cell proliferation. In addition, vascular endothelial growth factor C (VEGF-C) and chemokine (C-X-C motif) ligand 10 (CXCL-10) were also determined to be upregulated in epithelial cells, which suggests that uNK cells work synergistically with epithelial cells to support implantation and pregnancy. In addition, oriental herbal medicines have been used to treat infertility since ancient times; however, we failed to find that Zi Dan Yin can regulate these endometrial paracrine effects. Xin Gong, Zhenzhen Chen, Yanxia Liu, Qiudan Lu, and Zhe Jin Copyright © 2014 Xin Gong et al. All rights reserved. Vitamin D Status in Central Europe Wed, 26 Mar 2014 11:36:36 +0000 Little published information is available regarding epidemiological data on vitamin D status in the large geographical region of Central Europe (CE). We searched the journal literature with regard to 25(OH)D concentrations among community-dwelling or healthy people living in CE. 25(OH)D concentrations varied by age, season, study sample size, and methodological approach [i.e., 25(OH)D assay used]. Concentrations of 25(OH)D in CE appeared lower than 30 ng/mL, and the magnitude of hypovitaminosis D was similar to that reported in Western Europe. While most of the studies reviewed were cross-sectional studies, a longitudinal study was also included to obtain information on seasonal variability. The longitudinal study reported wintertime 25(OH)D values close to 21–23 ng/mL for all studied age groups, with a significant increase of 25(OH)D in August reaching 42 ng/mL for those aged 0–9 years, but only 21 ng/mL for the elderly aged 80–89 years. The decrease in 25(OH)D with respect to age was attributed to decreased time spent in the sun and decreased vitamin D production efficiency. Based on the literature review on vitamin D status in the CE populations, it can be concluded that 25(OH)vitamin D levels are on average below the 30 ng/mL level. Pawel Pludowski, William B. Grant, Harjit Pal Bhattoa, Milan Bayer, Vladyslav Povoroznyuk, Ema Rudenka, Heorhi Ramanau, Szabolcs Varbiro, Alena Rudenka, Elzbieta Karczmarewicz, Roman Lorenc, Justyna Czech-Kowalska, and Jerzy Konstantynowicz Copyright © 2014 Pawel Pludowski et al. All rights reserved. Adiponectin Expression in the Porcine Ovary during the Oestrous Cycle and Its Effect on Ovarian Steroidogenesis Wed, 26 Mar 2014 09:49:10 +0000 Adiponectin is an adipose-secreted hormone that regulates energy homeostasis and is also involved in the control of the reproductive system. The goal of the present study was to investigate changes in adiponectin gene and protein expression in porcine ovarian structures during the oestrous cycle and to examine the effects of in vitro administration of adiponectin on basal and gonadotrophin- and/or insulin-induced secretion of ovarian steroid hormones. Both gene and protein expression of adiponectin were enhanced during the luteal phase of the cycle. Adiponectin affected basal secretion of progesterone by luteal cells, oestradiol by granulosa cells, and testosterone by theca interna cells. The gonadotrophin/insulin-induced release of progesterone from granulosa and theca interna cells and the release of oestradiol and androstenedione from theca cells was also modified by adiponectin. In conclusion, the presence of adiponectin mRNA and protein in the porcine ovary coupled with our previous results indicating adiponectin receptors expression suggest that adiponectin may locally affect ovarian functions. The changes in adiponectin expression throughout the oestrous cycle seem to be dependent on the hormonal status of pigs related to the stage of the oestrous cycle. The effect of adiponectin on ovarian steroidogenesis suggests that this adipokine influences reproductive functions in pigs. Anna Maleszka, Nina Smolinska, Anna Nitkiewicz, Marta Kiezun, Katarzyna Chojnowska, Kamil Dobrzyn, Hubert Szwaczek, and Tadeusz Kaminski Copyright © 2014 Anna Maleszka et al. All rights reserved. Effect of Bile Acid on Fetal Lung in Rat Model of Intrahepatic Cholestasis of Pregnancy Sun, 23 Mar 2014 11:53:57 +0000 Objective. To determine the correlation between maternal bile acid (BA) level and fetal pulmonary surfactant in rats and study the effects of BA on fetal lung in rat model of intrahepatic cholestasis of pregnancy. Methods. Forty pregnant rats were treated with (A) 5.5 mg/kg BA, (B) 1.4 mg/kg BA, and (C) 1 ml physiological saline. Levels of total bile acid (TBA), ALT, AST, TBIL, DBIL, and SP-A were determined and the lungs of fetal rats were analyzed for pathological changes. Results. Groups A and B intervened with BA showed significant higher level of TBA in both maternal and fetal serum, more mortality rate of fetal rats, more concentration of SP-A in fetal serum, and wider alveolus mesenchyme of fetal rats than the control Group C. Higher level of BA associated with increased fetal risk and lower numerical density of mitochondria in type II alveolar epithelial cells. The levels of TBA in maternal serum were found to have significant positive correlation with those in fetal serum and SP-A level but negatively with the area of alveolus and the numerical density of lamellar body. Conclusions. The TBA level in maternal serum showed significant association with lung pathological changes in fetal rats. Ling Yu, Yiling Ding, Ting Huang, and Xiaoxia Huang Copyright © 2014 Ling Yu et al. All rights reserved. Prevalence of Nonclassic Congenital Adrenal Hyperplasia in Turkish Children Presenting with Premature Pubarche, Hirsutism, or Oligomenorrhoea Sun, 23 Mar 2014 08:14:10 +0000 Background. Nonclassic congenital adrenal hyperplasia (NCAH), caused by mutations in the gene encoding 21-hydroxylase, is a common autosomal recessive disorder. In the present work, our aim was to determine the prevalence of NCAH presenting as premature pubarche (PP), hirsutism, or polycystic ovarian syndrome (PCOS) and to evaluate the molecular spectrum of CYP21A2 mutations in NCAH patients. Methods. A total of 126 patients (122 females, 4 males) with PP, hirsutism, or PCOS were included in the present study. All patients underwent an ACTH stimulation test. NCAH was considered to be present when the stimulated 17-hydroxyprogesterone plasma level was >10 ng/mL. Results. Seventy-one of the 126 patients (56%) presented with PP, 29 (23%) with PCOS, and 26 (21%) with hirsutism. Six patients (4,7%) were diagnosed with NCAH based on mutational analysis. Four different mutations (Q318X, P30L, V281L, and P453S) were found in six NCAH patients. One patient with NCAH was a compound heterozygote for this mutation, and five were heterozygous. Conclusion. NCAH should be considered as a differential diagnosis in patients presenting with PP, hirsutism, and PCOS, especially in countries in which consanguineous marriages are prevalent. Cigdem Binay, Enver Simsek, Oguz Cilingir, Zafer Yuksel, Ozden Kutlay, and Sevilhan Artan Copyright © 2014 Cigdem Binay et al. All rights reserved. High Risk First Degree Relatives of Type 1 Diabetics: An Association with Increases in CXCR3+ T Memory Cells Reflecting an Enhanced Activity of Th1 Autoimmune Response Sun, 23 Mar 2014 00:00:00 +0000 We analyzed the level of (a) CXCR3+ (Th1) and CCR4+ (Th2) T memory cells (b) interferon-γ inducible chemokine (IP-10)(Th1) and thymus and activation-regulated chemokine (TARC)(Th2), in 51 first degree relatives (FDRs) of type 1 diabetics (T1D) (17 high risk FDRs (GADA+, IA-2+) and 34 low risk FDRs (GADA−, IA-2−)), 24 recent-onset T1D (R-T1D), and 18 healthy subjects. T memory subsets were analyzed by using four-color immunofluorescence staining and flowcytometry. IP-10 and TARC were determined by ELISA. High risk FDRs showed higher levels of CXCR3+ and lower level of CCR4+ T memory cells compared to low risk FDRs (64.98 ± 5.19 versus 42.13 ± 11.11; 29.46 ± 2.83 versus 41.90 ± 8.58%, resp., ). Simultaneously, both IP-10 and TARC levels were increased in high risk versus low risk FDRs (160.12 ± 73.40 versus 105.39 ± 71.30; 438.83 ± 120.62 versus 312.04 ± 151.14 pg/mL, ). Binary logistic regression analysis identified the level of CXCR3+ T memory cells as predictors for high risk FDRs, together with high levels of IP-10. The results imply that, in FDRs, the risk for T1D might be strongly influenced by enhanced activity of Th1 and diminished activity of Th2 autoimmune response. Tanja Milicic, Aleksandra Jotic, Ivanka Markovic, Katarina Lalic, Veljko Jeremic, Ljiljana Lukic, Natasa Rajkovic, Dušan Popadic, Marija Macesic, Jelena P. Seferovic, Sandra Aleksic, Jelena Stanarcic, Milorad Civcic, and Nebojsa M. Lalic Copyright © 2014 Tanja Milicic et al. All rights reserved. Recombinant Human Leptin Does Not Alter Gut Hormone Levels after Gastric Bypass but May Attenuate Sweet Cravings Thu, 20 Mar 2014 12:51:09 +0000 Bariatric surgery improves glucose homeostasis and alters gut hormones partly independent of weight loss. Leptin plays a role in these processes; levels are decreased following bariatric surgery, creating a relative leptin insufficiency. We previously showed that leptin administration in a weight-reduced state after Roux-en-Y gastric bypass (RYGB) caused no further weight loss. Here, we discuss the impact of leptin administration on gut hormones, glucostasis, and appetite. Weight stable women after RYGB were randomized to receive placebo or recombinant human metreleptin (0.05 mg/kg twice daily). At weeks 0 and 16, a liquid meal challenge was performed. Glucose, insulin, C-peptide, GLP-1, PYY, glucagon, and ghrelin (total, acyl, and desacyl) were measured fasting and postprandially. Appetite was assessed using a visual analog scale. Mean post-op period was months; mean BMI was  kg/m2. At 16 weeks, there was no significant change in weight within or between groups. Fasting PYY was significantly different between groups and the leptin group had lower sweets craving at week 16 than the placebo group (). No other differences were observed. Leptin replacement does not alter gut hormones or glucostasis but may diminish sweet cravings compared to placebo in this population of post-RYGB women. Rushika Conroy, Gerardo Febres, Donald J. McMahon, Michael O. Thorner, Bruce D. Gaylinn, Irene Conwell, Louis Aronne, and Judith Korner Copyright © 2014 Rushika Conroy et al. All rights reserved. Erectile Dysfunction in the Elderly: An Old Widespread Issue with Novel Treatment Perspectives Mon, 17 Mar 2014 10:18:00 +0000 Erectile dysfunction (ED) is one of the most common chronic diseases affecting men and its prevalence increases with aging. It is also the most frequently diagnosed sexual dysfunction in the older male population. A number of different diseases potentially worsening sexual function may occur in elderly people, together with polypharmacy. Related causes of ED are variable and can include arterial, neurogenic, hormonal, cavernosal, iatrogenic, and psychogenic causes. The aim of the present review was to examine the main aspects of erectile dysfunction going through epidemiology and pathophysiology and revise most of ED in elderly disabled men and in those affected with psychiatric disorders. Lastly we tried to focus on the main aspects of nonpharmacological and pharmacological treatments of ED and the recreational use in the elderly. Phosphodiesterase-5 inhibitors (PDE5-I) are commonly used for on-demand or chronic treatment of ED. It is widely known that PDE5-I have lower response rates in older men than in younger patients, but they have the advantages of ease of use and excellent safety profile, also in the elderly. The old and new PDE5-I as well as the alternative treatments for ED are extensively discussed. Pietro Gareri, Alberto Castagna, Davide Francomano, Gregorio Cerminara, and Pasquale De Fazio Copyright © 2014 Pietro Gareri et al. All rights reserved. Quality of Life and Sexual Health in the Aging of PCa Survivors Mon, 17 Mar 2014 06:40:08 +0000 Prostate cancer (PCa) is the most common malignancy in elderly men. The progressive ageing of the world male population will further increase the need for tailored assessment and treatment of PCa patients. The determinant role of androgens and sexual hormones for PCa growth and progression has been established. However, several trials on androgens and PCa are recently focused on urinary continence, quality of life, and sexual function, suggesting a new point of view on the whole endocrinological aspect of PCa. During aging, metabolic syndrome, including diabetes, hypertension, dyslipidemia, and central obesity, can be associated with a chronic, low-grade inflammation of the prostate and with changes in the sex steroid pathways. These factors may affect both the carcinogenesis processes and treatment outcomes of PCa. Any treatment for PCa can have a long-lasting negative impact on quality of life and sexual health, which should be assessed by validated self-reported questionnaires. In particular, sexual health, urinary continence, and bowel function can be worsened after prostatectomy, radiotherapy, or hormone treatment, mostly in the elderly population. In the present review we summarized the current knowledge on the role of hormones, metabolic features, and primary treatments for PCa on the quality of life and sexual health of elderly Pca survivors. Mauro Gacci, Elisabetta Baldi, Lara Tamburrino, Beatrice Detti, Lorenzo Livi, Cosimo De Nunzio, Andrea Tubaro, Stavros Gravas, Marco Carini, and Sergio Serni Copyright © 2014 Mauro Gacci et al. All rights reserved. Appetite Response among Those Susceptible or Resistant to Obesity Sun, 16 Mar 2014 00:00:00 +0000 An alternative approach in determining cause, treatment, and prevention of obesity is to study those who appear resistant to the obesogenic environment. We examined appetite responses in 33 obesity resistant individuals (ORI) versus 28 obesity susceptible individuals (OSI). Fingerprick blood samples to measure ghrelin, total peptide YY (PYY), leptin, glucose, and insulin along with appetite ratings were collected at baseline and 15, 30, 60, 120, and 180 min following consumption of a standardized meal. Fasting, area under the curve (AUC), peak/nadir, and time to peak/nadir were compared. Participants completed the three factor eating questionnaire (TFEQ). No significant differences were observed for ghrelin or PYY. Higher leptin concentrations in the OSI disappeared after controlling for percent body fat (%BF). Significant differences in appetite ratings included a lower hunger nadir among OSI compared with ORI (). Dietary restraint () and disinhibition () were lower in ORI compared with OSI, with and without adjustment for %BF. Given the differential body weight of the study groups, similar observed ghrelin concentrations were unexpected, perhaps indicating OSI and ORI respond differently to the same ghrelin concentration. Also ORI response to hunger appears different as they exhibit lower levels of dietary restraint and disinhibition compared with OSI. Rachel C. Brown, Rebecca T. McLay-Cooke, Sara L. Richardson, Sheila M. Williams, David R. Grattan, and Alexandra W.-A. H. Chisholm Copyright © 2014 Rachel C. Brown et al. All rights reserved. The Architecture of Risk for Type 2 Diabetes: Understanding Asia in the Context of Global Findings Thu, 13 Mar 2014 09:31:06 +0000 The prevalence of Type 2 diabetes is rising rapidly in both developed and developing countries. Asia is developing as the epicentre of the escalating pandemic, reflecting rapid transitions in demography, migration, diet, and lifestyle patterns. The effective management of Type 2 diabetes in Asia may be complicated by differences in prevalence, risk factor profiles, genetic risk allele frequencies, and gene-environment interactions between different Asian countries, and between Asian and other continental populations. To reduce the worldwide burden of T2D, it will be important to understand the architecture of T2D susceptibility both within and between populations. This review will provide an overview of known genetic and nongenetic risk factors for T2D, placing the results from Asian studies in the context of broader global research. Given recent evidence from large-scale genetic studies of T2D, we place special emphasis on emerging knowledge about the genetic architecture of T2D and the potential contribution of genetic effects to population differences in risk. Noraidatulakma Abdullah, John Attia, Christopher Oldmeadow, Rodney J. Scott, and Elizabeth G. Holliday Copyright © 2014 Noraidatulakma Abdullah et al. All rights reserved.