International Journal of Endocrinology The latest articles from Hindawi Publishing Corporation © 2015 , Hindawi Publishing Corporation . All rights reserved. Influence of CAG Repeat Polymorphism on the Targets of Testosterone Action Wed, 02 Sep 2015 09:51:44 +0000 In the last decade, ample evidence has demonstrated the growing importance of androgen receptor (AR) CAG repeat polymorphism in andrology. This genetic parameter is able to condition the peripheral effects of testosterone and therefore to influence male sexual function and fertility, cardiovascular risk, body composition, bone metabolism, the risk of prostate and testicular cancer, the psychiatric status, and the onset of neurodegenerative disorders. In this review, we extensively discuss the literature data and identify a role for AR CAG repeat polymorphism in conditioning the systemic testosterone effects. In particular, our main purpose was to provide an updated text able to shed light on the many and often contradictory findings reporting an influence of CAG repeat polymorphism on the targets of testosterone action. Giacomo Tirabassi, Angelo Cignarelli, Sebastio Perrini, Nicola delli Muti, Giorgio Furlani, Mariagrazia Gallo, Francesco Pallotti, Donatella Paoli, Francesco Giorgino, Francesco Lombardo, Loredana Gandini, Andrea Lenzi, and Giancarlo Balercia Copyright © 2015 Giacomo Tirabassi et al. All rights reserved. Low Growth Hormone Levels in Short-Stature Children with Pituitary Hyperplasia Secondary to Primary Hypothyroidism Wed, 02 Sep 2015 08:19:08 +0000 Objective. The follow-up of GH levels in short-stature children with pituitary hyperplasia secondary to primary hypothyroidism (PPH) is reported in a few cases. We aimed to observe changes in GH secretion in short-stature children with PPH. Methods. A total of 11 short-stature children with PPH accompanied by low GH levels were included. They received levothyroxine therapy after diagnosis. Their thyroid hormones, IGF-1, PRL, and pituitary height were measured at baseline and 3 months after therapy. GH stimulation tests were performed at baseline and after regression of thyroid hormones and pituitary. Results. At baseline, they had decreased GH peak and FT3 and FT4 levels and elevated TSH levels. Decreased IGF-1 levels were found in seven children. Elevated PRL levels and positive thyroid antibodies were found in 10 children. The mean pituitary height was  mm. After 3 months, FT3, FT4, and IGF-1 levels were significantly increased (all ), and values of TSH, PRL, and pituitary height were significantly decreased (all ). After 6 months, pituitary hyperplasia completely regressed. GH levels returned to normal in nine children and were still low in two children. Conclusion. GH secretion can be resolved in most short-stature children with PPH. Minghua Liu, Yanyan Hu, Guimei Li, and Wenwen Hu Copyright © 2015 Minghua Liu et al. All rights reserved. Changes in Bone Mineral Density and Metabolic Parameters after Pulsatile Gonadorelin Treatment in Young Men with Hypogonadotropic Hypogonadism Mon, 31 Aug 2015 06:03:58 +0000 To assess the prevalence of osteoporosis in young men with hypogonadotropic hypogonadism (HH) and to investigate the changes of BMD and metabolic parameters, a total of 22 young male patients with HH and 20 healthy controls were enrolled in the study. BMD, biochemical, and hormonal parameters were measured in two groups. Osteoporosis was more prevalent in HH patients (45.45%) than the control subjects (10.00%) (). The patients with HH had lower BMD in lumbar spine 2–4, femoral neck, and total hip (, for all) and higher fasting insulin (), HOMA-IR (), and SHBG () compared to the controls. After 6 months of pulsatile gonadorelin treatment, BMI () and BMD in lumbar spine 2–4, femoral neck, and total hip (, , and , resp.) increased dramatically and total cholesterol (), fasting insulin (), HOMA-IR (), and SHBG () decreased significantly in HH patients. The study shows a higher prevalence of osteoporosis in young men with HH. Long-term pulsatile gonadorelin treatment indicates a positive effect on BMD and metabolic parameters of HH patients. Chen-Xi Li, Song-Tao Tang, and Qiu Zhang Copyright © 2015 Chen-Xi Li et al. All rights reserved. Comparison of Conventional Open Thyroidectomy and Endoscopic Thyroidectomy via Breast Approach for Papillary Thyroid Carcinoma Wed, 26 Aug 2015 07:24:47 +0000 Purpose. The aim of this study was to evaluate the feasibility of endoscopic thyroidectomy via breast approach for papillary thyroid carcinoma (PTC). Methods. Between March 2008 and March 2013, 34 patients with PTC received endoscopic thyroidectomy (endo group) and 30 patients received conventional open thyroidectomy (open group). Patients in two groups underwent ipsilateral central compartment node dissection. The two groups were compared in terms of patient characteristics, perioperative clinical results, and postoperative complication. Results. The rates of lymph node metastasis in endo group and open group were 23.5% (8/34) and 13.3% (4/30), respectively, without statistically significant difference (). The mean number of lymph nodes dissected was 2.4 ± 2.9 in endoscopic group and 2.2 ± 1.9 in open group (). During the follow-up period, there was no recurrence or metastatic patients in two groups. All patients received the excellent cosmetic results in endo group, while 25 patients were satisfied with the cosmetic result and 5 were unsatisfied in the open group. Conclusions. The efficacy of endoscopic thyroidectomy via breast approach could be comparable to conventional open thyroidectomy in selected patients with PTC. Zhuo Tan, JiaLei Gu, QianBo Han, WenDong Wang, KeJing Wang, MingHua Ge, and JinBiao Shang Copyright © 2015 Zhuo Tan et al. All rights reserved. Tumor-Associated Mast Cells in Thyroid Cancer Wed, 26 Aug 2015 07:11:41 +0000 There is compelling evidence that the tumor microenvironment plays a major role in mediating aggressive features of cancer cells, including invasive capacity and resistance to conventional and novel therapies. Among the different cell populations that infiltrate cancer stroma, mast cells (MCs) can influence several aspects of tumor biology, including tumor development and progression, angiogenesis, lymphangiogenesis, and tissue remodelling. Thyroid cancer (TC), the most frequent neoplasia of the endocrine system, is characterized by a MC infiltrate, whose density correlates with extrathyroidal extension and invasiveness. Recent evidence suggests the occurrence of epithelial-to-mesenchymal transition (EMT) and stemness in human TC. The precise role of immune cells and their mediators responsible for these features in TC remains unknown. Here, we review the relevance of MC-derived mediators (e.g., the chemokines CXCL1/GRO-α, CXCL10/IP-10, and CXCL8/IL-8) in the context of TC. CXCL1/GRO-α and CXCL10/IP-10 appear to be involved in the stimulation of cell proliferation, while CXCL8/IL-8 participates in the acquisition of TC malignant traits through its ability to induce/enhance the EMT and stem-like features of TC cells. The inhibition of chemokine signaling may offer novel therapeutic approaches for the treatment of refractory forms of TC. Carla Visciano, Nella Prevete, Federica Liotti, and Gianni Marone Copyright © 2015 Carla Visciano et al. All rights reserved. Mechanisms of Normalisation of Bone Metabolism during Recovery from Hyperthyroidism: Potential Role for Sclerostin and Parathyroid Hormone Sun, 23 Aug 2015 12:12:22 +0000 Sclerostin, a protein expressed by osteocytes, is a negative regulator of bone formation. The aim of the study was to investigate the relationship between parathyroid hormone (PTH) and markers of bone metabolism and changes of sclerostin concentrations before and after treatment of hyperthyroidism. Patients and Methods. The study involved 33 patients (26 women), age (mean ± SD) 48 ± 15 years, with hyperthyroidism. Serum sclerostin, PTH, calcium, and bone markers [osteocalcin (OC) and collagen type I cross-linked C-telopeptide I (CTX)] were measured at diagnosis of hyperthyroidism and after treatment with thiamazole. Results. After treatment of hyperthyroidism a significant decrease in free T3 (FT3) and free T4 (FT4) concentrations was accompanied by marked decrease of serum sclerostin (from 43.7 ± 29.3 to 28.1 ± 18.4 pmol/L; ), OC (from 35.6 ± 22.0 to 27.0 ± 14.3 ng/mL; ), and CTX (from 0.49 ± 0.35 to 0.35 ± 0.23 ng/dL; ), accompanied by an increase of PTH (from 29.3 ± 14.9 to 39.8 ± 19.8; ). During hyperthyroidism there was a positive correlation between sclerostin and CTX (, ) and between OC and thyroid hormones (with FT3  , with FT4  , ). Conclusions. Successful treatment of hyperthyroidism results in a significant decrease in serum sclerostin and bone markers concentrations, accompanied by an increase of PTH. Elżbieta Skowrońska-Jóźwiak, Krzysztof C. Lewandowski, Zbigniew Adamczewski, Kinga Krawczyk-Rusiecka, and Andrzej Lewiński Copyright © 2015 Elżbieta Skowrońska-Jóźwiak et al. All rights reserved. Effect of Repetitive Glucose Spike and Hypoglycaemia on Atherosclerosis and Death Rate in Apo E-Deficient Mice Thu, 20 Aug 2015 12:51:49 +0000 Epidemiological data suggest that postprandial hyperglycaemia and hypoglycaemia are potential risk factors for cardiovascular disease. However, the effects of repetitive postprandial glucose spikes, repetitive hypoglycaemia, and their combination on the progression of atherosclerosis remain largely unknown. The present study investigated the effects of rapid rises and falls in glucose, and their combination, on the progression of atherosclerosis in apolipoprotein (apo) E-deficient mice. In this study, apo E-deficient mice with forced oral administration of glucose twice daily for 15 weeks were used as a model of repetitive postprandial glucose spikes, and apo E-deficient mice given an intraperitoneal injection of insulin once a week for 15 weeks were used as a model of repetitive hypoglycaemia. In addition, we established a model of both repetitive postprandial glucose spikes and hypoglycaemia by combining the above interventions. Atherosclerosis was evaluated in all mice by oil red O staining. Administration of ipragliflozin, a selective inhibitor of sodium-glucose cotransporter 2, in the mouse model of repetitive glucose spikes inhibited the progression of atherosclerosis, whereas long-term repetitive glucose spikes, repetitive hypoglycaemia, and their combination had no significant impact on atherosclerosis. However, repetitive hypoglycaemia was associated with poor survival rate. The results showed that repetitive hypoglycaemia reduces the survival rate without associated progression of atherosclerosis in apo E-deficient mice. Kenichi Nakajima, Tomoya Mita, Yusuke Osonoi, Kosuke Azuma, Toshiyuki Takasu, Yoshio Fujitani, and Hirotaka Watada Copyright © 2015 Kenichi Nakajima et al. All rights reserved. Multiple Factors Related to the Secretion of Glucagon-Like Peptide-1 Thu, 20 Aug 2015 11:53:08 +0000 The glucagon-like peptide-1 is secreted by intestinal L cells in response to nutrient ingestion. It regulates the secretion and sensitivity of insulin while suppressing glucagon secretion and decreasing postprandial glucose levels. It also improves beta-cell proliferation and prevents beta-cell apoptosis induced by cytotoxic agents. Additionally, glucagon-like peptide-1 delays gastric emptying and suppresses appetite. The impaired secretion of glucagon-like peptide-1 has negative influence on diabetes, hyperlipidemia, and insulin resistance related diseases. Thus, glucagon-like peptide-1-based therapies (glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors) are now well accepted in the management of type 2 diabetes. The levels of glucagon-like peptide-1 are influenced by multiple factors including a variety of nutrients. The component of a meal acts as potent stimulants of glucagon-like peptide-1 secretion. The levels of its secretion change with the intake of different nutrients. Some drugs also have influence on GLP-1 secretion. Bariatric surgery may improve metabolism through the action on GLP-1 levels. In recent years, there has been a great interest in developing effective methods to regulate glucagon-like peptide-1 secretion. This review summarizes the literature on glucagon-like peptide-1 and related factors affecting its levels. XingChun Wang, Huan Liu, Jiaqi Chen, Yan Li, and Shen Qu Copyright © 2015 XingChun Wang et al. All rights reserved. The Relationship between Serum Ferritin and Insulin Resistance in Different Glucose Metabolism in Nonobese Han Adults Wed, 19 Aug 2015 13:24:37 +0000 The exact mechanism through which elevated serum ferritin promotes the development of type 2 diabetes is unknown. This study showed that ferritin concentration in impaired glucose regulation and newly diagnosed diabetes mellitus subjects of nonobesity already significantly increased when compared with normal glucose tolerant subjects of nonobesity. Elevated serum ferritin levels are associated with insulin resistance and may be not associated with the decline of insulin beta cells in different status of glucose tolerance in nonobese Han adults. Bo-wei Liu, Xu-min Xuan, Jun-ru Liu, Fang-ning Li, and Fu-Zai Yin Copyright © 2015 Bo-wei Liu et al. All rights reserved. Waist-to-Hip Ratio, but Not Body Mass Index, Is Associated with Testosterone and Estradiol Concentrations in Young Women Mon, 17 Aug 2015 13:52:44 +0000 We studied if testosterone and estradiol concentrations are associated with specific female waist-to-hip ratios (WHRs) and body mass indices (BMIs). Participants were 187 young women from which waist, hips, weight, and height were measured. In addition, participants informed on which day of their menstrual cycle they were and provided a 6 mL saliva sample. Ninety-one of them were in the follicular phase and 96 in the luteal phase. Only in the fertile phase of the menstrual cycle we found a significant interaction between testosterone and estradiol affecting WHR (, adjusted ). Women with the highest levels of both hormones had the lowest WHRs, while women with low estradiol and high testosterone showed the highest WHRs. BMI significantly increased as testosterone increased in female in their nonfertile days. Ricardo Mondragón-Ceballos, Mónica Dafne García Granados, Ana Lilia Cerda-Molina, Roberto Chavira-Ramírez, and Leonor Estela Hernández-López Copyright © 2015 Ricardo Mondragón-Ceballos et al. All rights reserved. Ferritin as a Risk Factor for Glucose Intolerance amongst Men and Women Originating from the Indian Subcontinent Wed, 12 Aug 2015 12:15:12 +0000 Background. Serum ferritin predicts the onset of diabetes; however, this relationship is not clear amongst South Asians, a population susceptible to glucose intolerance and anaemia. Objective. This study tests whether ferritin levels reflect glucose tolerance in South Asians, independent of lifestyle exposures associated with Indian or British residence. Methods. We randomly sampled 227 Gujaratis in Britain (49.8 (14.4) years, 50% men) and 277 contemporaries living in Gujarati villages (47.6 (11.8) years, 41% men). Both groups underwent a 75 g oral-glucose-tolerance test. We evaluated lifestyle parameters with standardised questionnaires and conducted comprehensive clinical and lab measurements. Results. Across sites, the age-adjusted prevalence of diabetes was 9.8%. Serum ferritin was higher amongst diabetics (), irrespective of site, gender, and central obesity (), and was associated with fasting and postchallenge glucose, anthropometry, blood pressure, triglycerides, and nonesterified fatty acids (). Diabetes was less in those with low ferritin (<20 mg/mL), , and risk estimate = 0.35 (95% CI 0.15–0.81), as were blood pressure and metabolic risk factors. On multivariate analysis, diabetes was independently associated with ferritin () and age (). Conclusion. Ferritin levels are positively associated with glucose intolerance in our test groups, independent of gender and Indian or UK lifestyle factors. Elizabeth A. Hughes, Jeetesh V. Patel, Zosia Bredow, Paramjit S. Gill, Julia Chackathayil, Elif S. Agaoglu, Paul Flinders, and Rebecca Mirrielees Copyright © 2015 Elizabeth A. Hughes et al. All rights reserved. Involvement of the Androgen and Glucocorticoid Receptors in Bladder Cancer Mon, 10 Aug 2015 12:46:24 +0000 Bladder cancer is encountered worldwide having been associated with a host of environmental and lifestyle risk factors. The disease has a male to female prevalence of 3 : 1. This disparity has raised the possibility of the androgen receptor (AR) pathway being involved in the genesis of the disease; indeed, research has shown that AR is involved in and is likely a driver of bladder cancer. Similarly, an inflammatory response has been implicated as a major player in bladder carcinogenesis. Consistent with this concept, recent work on anti-inflammatory glucocorticoid signaling points to a pathway that may impact bladder cancer. The glucocorticoid receptor- (GR-) α isoform has an important role in suppressing inflammatory processes, which may be attenuated by AR in the development of bladder cancer. In addition, a GR isoform that is inhibitory to GRα, GRβ, is proinflammatory and has been shown to induce cancer growth. In this paper, we review the evidence of inflammatory mediators and the relationship of AR and GR isoforms as they relate to the propensity for bladder cancer. Lucien McBeth, Maria Grabnar, Steven Selman, and Terry D. Hinds Jr. Copyright © 2015 Lucien McBeth et al. All rights reserved. Improvement in Depressive Symptoms Is Associated with Reduced Oxidative Damage and Inflammatory Response in Type 2 Diabetic Patients with Subsyndromal Depression: The Results of a Randomized Controlled Trial Comparing Psychoeducation, Physical Exercise, and Enhanced Treatment as Usual Mon, 10 Aug 2015 11:36:37 +0000 Aims. To examine one-year changes in oxidative damage and inflammation level in type 2 diabetic patients undergoing behavioral treatment for subsyndromal depression. Materials and Methods. A randomized controlled comparison of psychoeducation (A), physical exercise (B), and enhanced treatment as usual (C) was performed in 209 eligible subjects in a tertiary diabetes care setting. Depressive symptoms (primary outcome) and selected biomarkers of oxidative damage and inflammation (secondary outcomes) were assessed at baseline and six- and twelve-month follow-up. Results. Out of the 74, 67, and 68 patients randomised into groups A, B, and C, respectively, 201 completed the interventions, and 179 were analysed. Participants in all three groups equally improved in depressive symptoms from baseline to one-year follow-up (repeated measures ANOVA; , , ). Urinary 8-oxo-deoxyguanosine (u-8-oxodG) decreased (, , ), as did sialic acid and leukocytes (, and , , resp.; ), while uric acid increased (, , ) in all subjects during one year. Improvement of depressive symptoms at 6 months significantly predicted one-year reduction in u-8-oxodG (, ). Conclusion. Simple behavioral interventions are capable not only of alleviating depressive symptoms, but also of reducing the intensity of damaging oxidative/inflammatory processes in type 2 diabetic patients with subsyndromal depression. This trial is registered with ISRCTN05673017. Marijana Vučić Lovrenčić, Mirjana Pibernik-Okanović, Mario Šekerija, Manja Prašek, Dea Ajduković, Jadranka Kos, and Norbert Hermanns Copyright © 2015 Marijana Vučić Lovrenčić et al. All rights reserved. Is Stimulated Thyroglobulin Necessary after Ablation in All Patients with Papillary Thyroid Carcinoma and Basal Thyroglobulin Detectable by a Second-Generation Assay? Sun, 09 Aug 2015 13:49:15 +0000 Objective. To evaluate the percentage of elevated stimulated thyroglobulin (sTg) and persistent or recurrent disease (PRD) in patients with detectable basal Tg < 0.3 ng/mL. Methods. The sample consisted of 130 patients with papillary thyroid carcinoma (PTC) who were at low risk of PRD and who had neck ultrasound (US) without abnormalities, negative anti-Tg antibodies (TgAb), and detectable basal Tg < 0.3 ng/mL about 6 months after ablation. Results. sTg was <1 ng/mL in 88 patients (67.7%), between 1 and 2 ng/mL in 26 (20%), and ≥2 ng/mL in 16 (12.3%). Imaging methods revealed the absence of tumors in 16 patients with elevated sTg. During follow-up, Tg increased to 0.58 ng/mL in one patient and lymph node metastases were detected. Sixty-nine patients continued to have detectable Tg < 0.3 ng/mL and US revealed recurrence in only one patient. Sixty patients progressed to persistently undetectable Tg without apparent disease on US. Conclusions. In low-risk patients with PTC who have detectable basal Tg < 0.3 ng/mL after ablation, negative TgAb, and US, persistent disease is rare and eventual recurrences can be detected by basal Tg elevation and/or subsequent US assessments, with follow-up without sTg being an “alternative” to Tg stimulation. Pedro Weslley Rosario, Gabriela Franco Mourão, and Maria Regina Calsolari Copyright © 2015 Pedro Weslley Rosario et al. All rights reserved. Usefulness of an Image Fusion Model Using Three-Dimensional CT and MRI with Indocyanine Green Fluorescence Endoscopy as a Multimodal Assistant System in Endoscopic Transsphenoidal Surgery Mon, 03 Aug 2015 07:24:55 +0000 Purpose. We investigate the usefulness of multimodal assistant systems using a fusion model of preoperative three-dimensional (3D) computed tomography (CT) and magnetic resonance imaging (MRI) along with endoscopy with indocyanine green (ICG) fluorescence in establishing endoscopic endonasal transsphenoidal surgery (ETSS) as a more effective treatment procedure. Methods. Thirty-five consecutive patients undergoing ETSS in our hospital between April 2014 and March 2015 were enrolled in the study. In all patients, fusion models of 3D-CT and MRI were created by reconstructing preoperative images. In addition, in 10 patients, 12.5 mg of ICG was intravenously administered, allowing visualization of surrounding structures. We evaluated the accuracy and utility of these combined modalities in ETSS. Results. The fusion model of 3D-CT and MRI clearly demonstrated the complicated structures in the sphenoidal sinus and the position of the internal carotid arteries (ICAs), even with extensive tumor infiltration. ICG endoscopy enabled us to visualize the surrounding structures by the phasic appearance of fluorescent signals emitted at specific consecutive elapsed times. Conclusions. Preoperative 3D-CT and MRI fusion models with intraoperative ICG endoscopy allowed distinct visualization of vital structures in cases where tumors had extensively infiltrated the sphenoidal sinus. Additionally, the ICG endoscope was a useful real-time monitoring tool for ETSS. Akihiro Inoue, Takanori Ohnishi, Shohei Kohno, Naoya Nishida, Yawara Nakamura, Yoshihiro Ohtsuka, Shirabe Matsumoto, and Shiro Ohue Copyright © 2015 Akihiro Inoue et al. All rights reserved. Succinate Dehydrogenase Loss in Familial Paraganglioma: Biochemistry, Genetics, and Epigenetics Wed, 29 Jul 2015 09:04:57 +0000 It is counterintuitive that metabolic defects reducing ATP production can cause, rather than protect from, cancer. Yet this is precisely the case for familial paraganglioma, a form of neuroendocrine malignancy caused by loss of succinate dehydrogenase in the tricarboxylic acid cycle. Here we review biochemical, genetic, and epigenetic considerations in succinate dehydrogenase loss and present leading models and mysteries associated with this fascinating and important tumor. Yeng F. Her and L. James Maher III Copyright © 2015 Yeng F. Her and L. James Maher III. All rights reserved. Beneficial Effects of the mTOR Inhibitor Everolimus in Patients with Advanced Medullary Thyroid Carcinoma: Subgroup Results of a Phase II Trial Wed, 29 Jul 2015 07:10:38 +0000 Objective. Until recently, advanced medullary thyroid cancer (MTC) had few treatment options except surgery. The mTOR inhibitor everolimus has shown encouraging results in neuroendocrine tumors. As part of a prospective phase II study, we analyzed the safety and efficacy of everolimus in advanced MTC. Methods. Seven patients with per RECIST 1.1 documented advanced MTC were included and received everolimus 10 mg daily. The primary objective was determining treatment efficacy. Secondary endpoints included progression-free survival (PFS), overall survival (OS), toxicity, and pharmacokinetics (PK). Results. Median follow-up duration was 28 weeks (17–147). Five patients (71%) showed SD, of which 4 (57%) showed SD >24 weeks. Median PFS and OS were 33 (95%CI: 8–56) and 30 (95%CI: 15–45) weeks, respectively. Toxicity was predominantly grade 1/2 and included mucositis (43%), fatigue (43%), and hypertriglyceridemia (43%). Four MTCs harbored the somatic RET mutation c.2753T>C, p.Met918Thr. The best clinical response was seen in a MEN2A patient. PK characteristics were consistent with phase I data. One patient exhibited extensive toxicity accompanying elevated everolimus plasma concentrations. Conclusions. This study suggests that everolimus exerts clinically relevant antitumor activity in patients with advanced MTC. Given the high level of clinical benefit and the relatively low toxicity profile, further investigation of everolimus in these patients is warranted. T. C. Schneider, D. de Wit, T. P. Links, N. P. van Erp, J. J. M. van der Hoeven, H. Gelderblom, T. van Wezel, R. van Eijk, H. Morreau, H. J. Guchelaar, and E. Kapiteijn Copyright © 2015 T. C. Schneider et al. All rights reserved. Alpha-Lipoic Acid Attenuates Cerebral Ischemia and Reperfusion Injury via Insulin Receptor and PI3K/Akt-Dependent Inhibition of NADPH Oxidase Wed, 29 Jul 2015 06:38:35 +0000 Alpha-lipoic acid (ALA) has various pharmacological effects such as antioxidative, anti-inflammatory, and antiapoptotic properties. In the present study, administration of ALA (40 mg/kg, i.p.) for 3 days resulted in a significant decrease in neuronal deficit score and infarct volume and a significant increase in grip time and latency time in Morris water maze at 48 h after middle cerebral artery occlusion and reperfusion (MCAO/R) in rats. ALA also reduced the increased TUNEL-positive cells rate and the enhanced caspase-3 activity induced by MCAO/R. However, the underlying mechanisms remain poorly understood. In this study, we found that ALA could activate insulin receptor and PI3K/Akt signaling pathways, inhibit the expression and activity of NADPH oxidase, and subsequently suppress the generation of superoxide and the augment of oxidative stress indicators including MDA, protein carbonylation, and 8-OHdG. In conclusion, ALA attenuates cerebral ischemia and reperfusion injury via insulin receptor and PI3K/Akt-dependent inhibition of NADPH oxidase. Yinhua Dong, Hongxin Wang, and Zefeng Chen Copyright © 2015 Yinhua Dong et al. All rights reserved. Osteoporosis 2014 Tue, 28 Jul 2015 13:27:28 +0000 Ling-Qing Yuan, Hong W. Ouyang, Thomas Levin Andersen, Yebin Jiang, Francesco Pantano, and Peng-Fei Shan Copyright © 2015 Ling-Qing Yuan et al. All rights reserved. Lactoferrin Induces Osteoblast Growth through IGF-1R Tue, 28 Jul 2015 11:20:08 +0000 Objectives. To investigate the role of the IGF-1R by which lactoferrin induces osteoblast growth. Methods. Osteoblast received 5 d lactoferrin intervention at a concentration of 0.1, 1, 10, 100, and 1000 μg/mL, and the IGF-1 and IGF-1R were detected using RT-PCR and western blot. The osteoblast into the control, 100 μg/mL lactoferrin, Neo-scramble (NS, empty vector), NS + 100 μg/mL lactoferrin, shIGF-1R and shIGF-1R + 100 μg/mL lactoferrin group. We test the apoptosis and proliferation and the level of PI3K and RAS in osteoblasts after 5 d intervention. Results. (1) 1, 10, 100, and 1000 μg/mL lactoferrin induced the expression of IGF-1 mRNA and protein. 10 μg/mL and 100 μg/mL lactoferrin induced the expression of IGF-1R mRNA and protein. (2) Lactoferrin (100 μg/mL) induced osteoblast proliferation while inhibiting apoptosis. Osteoblasts with silenced IGF-1R exhibited decreased proliferation but increased apoptosis. MMT staining and flow cytometry both indicated that there was no significant difference between the shIGF-1R group and the shIGF-1R + 100 μg/mL lactoferrin group. (3) Lactoferrin (100 μg/mL) induced PI3K and RAS phosphorylation and silence of IGF-1R resulted in decreased p-PI3K and p-RAS expression. Lactoferrin-treated shIGF-1R cells showed significantly higher level of p-PI3K and p-RAS when compared with shIGF-1R. Conclusion. Lactoferrin induced IGF-1/IGF-1R in a concentration-dependent manner. Lactoferrin promoted osteoblast proliferation while inhibiting apoptosis through IGF-1R. Lactoferrin activated PI3K and RAS phosphorylation via an IGF-1R independent pathway. Jian-Ming Hou, En-Yu Chen, Fan Lin, Qing-Ming Lin, Ying Xue, Xu-Hua Lan, and Man Wu Copyright © 2015 Jian-Ming Hou et al. All rights reserved. Addressing Inpatient Glycaemic Control with an Inpatient Glucometry Alert System Tue, 28 Jul 2015 10:11:31 +0000 Background. Poor inpatient glycaemic control has a prevalence exceeding 30% and results in increased length of stay and higher rates of hospital complications and inpatient mortality. The aim of this study was to improve inpatient glycaemic control by developing an alert system to process point-of-care blood glucose (POC-BG) results. Methods. Microsoft Excel Macros were developed for the processing of daily glucometry data downloaded from the Cobas IT database. Alerts were generated according to ward location for any value less than 4 mmol/L (hypoglycaemia) or greater than 15 mmol/L (moderate-severe hyperglycaemia). The Diabetes Team provided a weekday consult service for patients flagged on the daily reports. This system was implemented for a 60-day period. Results. There was a statistically significant 20% reduction in the percentage of hyperglycaemic patient-day weighted values >15 mmol/L compared to the preimplementation period without a significant change in the percentage of hypoglycaemic values. The time-to-next-reading after a dysglycaemic POC-BG result was reduced by 14% and the time-to-normalization of a dysglycaemic result was reduced from 10.2 hours to 8.4 hours. Conclusion. The alert system reduced the percentage of hyperglycaemic patient-day weighted glucose values and the time-to-normalization of blood glucose. J. N. Seheult, A. Pazderska, P. Gaffney, J. Fogarty, M. Sherlock, J. Gibney, and G. Boran Copyright © 2015 J. N. Seheult et al. All rights reserved. The Clinicopathological Features of BRAF Mutated Papillary Thyroid Cancers in Chinese Patients Mon, 27 Jul 2015 13:36:24 +0000 The mutation is commonly found in papillary thyroid cancers (PTCs) at different frequencies in different regions. However, the association between the mutation and clinicopathological features in Chinese PTC patients is unknown. A total of 543 Chinese patients with histologically confirmed PTC were enrolled in this study. For the BRAF mutation assay, the target fragments were amplified and sequenced with an ABI 3500 gene analyzer. In 170 of 543 samples (31.3%), the mutation was detected. In the bivariate analysis, the mutation showed an association with bilaterality, tumor size, extrathyroidal invasion, and lymph node metastases (LNM). However, in the multivariate analysis, the mutation was positively related to only tumor size (>1 cm) and extrathyroidal invasion. In addition, the multivariate analysis also showed that the age at diagnosis (<45 y) and tumor size (>1 cm) were independent predictors for LNM. In this study, the mutation is positively associated with worse prognostic factors, including larger tumor size and the tumor extending to the thyroid capsule or extrathyroidal region; however, it is not an independent predictor for LNM. Li-Bo Yang, Lin-Yong Sun, Yong Jiang, Ying Tang, Zhi-Hui Li, Hong-Ying Zhang, Hong Bu, and Feng Ye Copyright © 2015 Li-Bo Yang et al. All rights reserved. Comparison of the Spine and Hip BMD Assessments Derived from Quantitative Computed Tomography Mon, 27 Jul 2015 13:23:00 +0000 Quantification of bone mineral density (BMD) is being used as the main method to diagnose osteoporosis. Dual-energy X-ray absorptiometry (DXA) is the most common tools for measuring BMD. Compared to DXA, quantitative computed tomography (QCT) can determine in three dimensions the true volumetric BMD (vBMD) at any skeletal site. In addition to the spine, the hip is an important site for axial BMD measurement. This study examines lumbar spine and hip BMD of Chinese adults by QCT. Age related changes in bone mass derived by QCT measurements were determined. The osteoporosis QCT detection rates at the spine and hip are assessed in both female and male, and agreement of skeletal status category between the spine and hip in older adults is also assessed. Xiao-Hui Ma, Wei Zhang, Yan Wang, Peng Xue, and Yu-Kun Li Copyright © 2015 Xiao-Hui Ma et al. All rights reserved. Micro/Nanostructures and Mechanical Properties of Trabecular Bone in Ovariectomized Rats Mon, 27 Jul 2015 13:17:41 +0000 Bone mechanical properties encompass both geometric and material factors, while the effects of estrogen deficiency on the material and structural characteristics of bone at micro- to nanoscales are still obscure. We performed a series of combined methodological experiments, including nanoindentation assessment of intrinsic material properties, atomic force microscopy (AFM) characterization of trabecular (Tb) nanostructure, and Tb microarchitecture and 2D BMD. At 15 weeks after surgery, we found significantly less Tb bone mineral density (BMD) at organ (−27%) and at tissue level (−12%), Tb bone volume fraction (−29%), Tb thickness (−14%), and Tb number (−17%) in ovariectomy (OVX) rats than in sham operated (SHAM) rats, while the structure model index (+91%) and Tb separation (+19%) became significantly greater. AFM images showed lower roughness Tb surfaces with loosely packed large nodular structures and less compacted interfibrillar space in OVX than in SHAM. However, no statistically significant changes were in the Tb intrinsic material properties—nanoindentation hardness, elastic modulus, and plastic deformation—nanoindentation depths, and residual areas. Therefore, estrogen deprivation results in a dramatic deterioration in Tb micro/nanoarchitectures, 3D volumetric BMD at both organ and tissue levels, and 2D BMD, but not in the nanomechanical properties of the trabeculae per se. Shidi Hu, Jin Li, Lu Liu, Ruchun Dai, Zhifeng Sheng, Xianping Wu, Xiqiao Feng, Xuefeng Yao, Eryuan Liao, Evan Keller, and Yebin Jiang Copyright © 2015 Shidi Hu et al. All rights reserved. Mechanism and Treatment Strategy of Osteoporosis after Transplantation Mon, 27 Jul 2015 13:11:33 +0000 Osteoporosis (OP) has emerged as a frequent and devastating complication of organ solid transplantation process. Bone loss after organ transplant is related to adverse effects of immunosuppressants on bone remodeling and bone quality. Many factors contribute to the pathogenesis of OP in transplanted patients. Many mechanisms of OP have been deeply approached. Drugs for OP can be generally divided into “bone resorption inhibitors” and “bone formation accelerators,” the former hindering bone resorption by osteoclasts and the latter increasing bone formation by osteoblasts. Currently, bisphosphonates, which are bone resorption inhibitors drugs, are more commonly used clinically than others. Using the signaling pathway or implantation bone marrow stem cell provides a novel direction for the treatment of OP, especially OP after transplantation. This review addresses the mechanism of OP and its correlation with organ transplantation, lists prevention and management of bone loss in the transplant recipient, and discusses the recipients of different age and gender. Lei Song, Xu-Biao Xie, Long-Kai Peng, Shao-Jie Yu, and Ya-Ting Peng Copyright © 2015 Lei Song et al. All rights reserved. Validity of 12-Month Falls Recall in Community-Dwelling Older Women Participating in a Clinical Trial Mon, 27 Jul 2015 12:54:50 +0000 Objectives. To compare 12-month falls recall with falls reported prospectively on daily falls calendars in a clinical trial of women aged ≥70 years. Methods. 2,096 community-dwelling women at high risk of falls and/or fracture completed a daily falls calendar and standardised interviews when falls were recorded, for 12 months. Data were compared to a 12-month falls recall question that categorised falls status as “no falls,” “a few times,” “several,” and “regular” falls. Results. 898 (43%) participants reported a fall on daily falls calendars of whom 692 (77%) recalled fall(s) at 12 months. Participants who did not recall a fall were older (median 79.3 years versus 77.8 years, ). Smaller proportions of fallers who sustained an injury or accessed health care failed to recall a fall (all ). Among participants who recalled “no fall,” 85% reported zero falls on daily calendars. Few women selected falls categories of “several times” or “regular” (4.1% and 0.4%, resp.) and the sensitivity of these categories was low (30% to 33%). Simply categorising participants into fallers or nonfallers had 77% sensitivity and 94% specificity. Conclusion. For studies where intensive ascertainment of falls is not feasible, 12-month falls recall questions with fewer responses may be an acceptable alternative. Kerrie M. Sanders, Amanda L. Stuart, David Scott, Mark A. Kotowicz, and Geoff C. Nicholson Copyright © 2015 Kerrie M. Sanders et al. All rights reserved. Effects of Alendronate Sodium Content on the Interface Strengths of Composite Acrylic Bone Cement Mon, 27 Jul 2015 12:25:42 +0000 Objective. Aim to study how the content of alendronate affected shear strengths at bone-bone cement-metal interfaces. Methods. All samples were divided into 6 groups, G0–G5. On the 1st and 60th day after surgery, bone-bone cement interface shear strengths and bone densities were examined. Interface strengths of metal-bone cement specimens were studied before immersion and 4 weeks after immersion. Results. On the 60th day, bone-bone cement interface shear strengths and bone densities showed significant differences (), and compared with G0, G2–G5 values increased significantly (), and the peak value was met in G3. Compared with the 1st day, on the 60th postoperative day both factors decreased significantly in G0 and G1 (). Four weeks after immersion, with the increasing dose of alendronate, the shear strengths decreased gradually and in G5 decreased significantly (). Compared with before immersion, the metal-bone cement interface strengths decreased significantly 4 weeks after immersion (). Conclusions. 50–500 mg alendronate in 50 g cement powders could prevent the decrease of shear strengths at bone-bone cement interfaces and had no effect on metal-bone cement interface strengths. While the addition dose was 100 mg, bone cement showed the best strengths. De-Ye Song, Xin-Zhan Mao, Mu-liang Ding, and Jiang-Dong Ni Copyright © 2015 De-Ye Song et al. All rights reserved. Low Magnesium Exacerbates Osteoporosis in Chronic Kidney Disease Patients with Diabetes Mon, 27 Jul 2015 11:06:13 +0000 The aim of this study is to investigate the impact of serum Mg on bone mineral metabolism in chronic kidney disease (CKD) patients with or without diabetes. A total of 56 CKD patients not receiving dialysis were recruited and divided into two groups, one group of 27 CKD patients with diabetes and another group of 29 CKD patients without diabetes. Biochemical determinations were made, and the estimated glomerular filtration rate (eGFR) was measured. Bone mineral density was measured by dual-energy X-ray absorptiometry. Serum Mg was inversely correlated with serum Ca and positively correlated with serum parathyroid hormone (PTH) , alkaline phosphatase , and phosphate in the CKD patients with diabetes. The CKD patients with diabetes had lower serum albumin and a higher proportion of hypomagnesemia and osteoporosis than the nondiabetic patients did . Serum Mg was inversely correlated with eGFR in the CKD patients with or without diabetes . Serum Mg showed an inverse correlation with 25-hydroxyvitamin D in CKD patients without diabetes . Furthermore, the diabetic CKD patients with low serum Mg had a lower iPTH and a higher serum Ca/Mg ratio than the other CKD patients. The lower serum Mg subgroup showed a higher incidence of osteoporosis than the moderate and higher serum Mg subgroups did (66.7%, 39.4%, and 29.4%, resp.). In conclusion, low serum Mg may impact iPTH and exacerbates osteoporosis in CKD patients, particularly with diabetes. Jui-Hua Huang, Fu-Chou Cheng, and Hsu-Chen Wu Copyright © 2015 Jui-Hua Huang et al. All rights reserved. The Inhibitory Effect of Alisol A 24-Acetate from Alisma canaliculatum on Osteoclastogenesis Mon, 27 Jul 2015 10:36:24 +0000 Osteoporosis is a disease that decreases bone mass. The number of patients with osteoporosis has been increasing, including an increase in patients with bone fractures, which lead to higher medical costs. Osteoporosis treatment is all-important in preventing bone loss. One strategy for osteoporosis treatment is to inhibit osteoclastogenesis. Osteoclasts are bone-resorbing multinucleated cells, and overactive osteoclasts and/or their increased number are observed in bone disorders including osteoporosis and rheumatoid arthritis. Bioactivity-guided fractionations led to the isolation of alisol A 24-acetate from the dried tuber of Alisma canaliculatum. Alisol A 24-acetate inhibited RANKL-mediated osteoclast differentiation by downregulating NFATc1, which plays an essential role in osteoclast differentiation. Furthermore, it inhibited the expression of DC-STAMP and cathepsin K, which are related to cell-cell fusion of osteoclasts and bone resorption, respectively. Therefore, alisol A 24-acetate could be developed as a new structural scaffold for inhibitors of osteoclast differentiation in order to develop new drugs against osteoporosis. Kwang-Jin Kim, Alain Simplice Leutou, Jeong-Tae Yeon, Sik-Won Choi, Seong Hwan Kim, Sung-Tae Yee, Kyung Hee Choi, Sang-Jip Nam, and Young-Jin Son Copyright © 2015 Kwang-Jin Kim et al. All rights reserved. Vitamin D and Osteoporosis in HIV/HCV Coinfected Patients: A Literature Review Mon, 27 Jul 2015 10:34:52 +0000 Vitamin D deficiency further increases the risk of osteoporosis in HIV-positive patients coinfected with hepatitis C virus (HCV); however, it is still unclear whether HCV-related increased fracture risk is a function of the severity of liver disease. The aim of this review was to identify studies on associative vitamin D deficiency patterns in high-risk populations such as HIV/HCV coinfected patients. We did this by searching MEDLINE and EMBASE databases, from inception to August 2014, and included bibliographies. The final 12 articles selected are homogeneous in terms of age but heterogeneous in terms of sample size, participant recruitment, and data source. Most of the HIV/HCV coinfected patients have less than adequate levels of vitamin D. After reviewing the selected articles, we concluded that vitamin D deficiency should be regarded as a continuum and that the lower limit of the ideal range is debatable. We found that vitamin D deficiency might influence liver disease progression in HIV/HCV coinfected patients. Methodological issues in evaluating vitamin D supplementation as a relatively inexpensive therapeutic option are discussed, as well as the need for future research, above all on its role in reducing the risk of HCV-related fracture by modifying liver fibrosis progression. Paola Di Carlo, Lucia Siracusa, Giovanni Mazzola, Piero Colletti, Maurizio Soresi, Lydia Giannitrapani, Valentina Li Vecchi, and Giuseppe Montalto Copyright © 2015 Paola Di Carlo et al. All rights reserved.