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1.  Consequence of Menin Deficiency in Mouse Adipocytes Derived by In Vitro Differentiation 
Lipoma in patients with the multiple endocrine neoplasia type 1 (MEN1) syndrome is a type of benign fat-cell tumor that has biallelic inactivation of MEN1 that encodes menin and could serve as a model to investigate normal and pathologic fat-cell (adipocyte) proliferation and function. The role of menin and its target genes in adipocytes is not known. We used in vitro differentiation to derive matched normal and menin-deficient adipocytes from wild type (WT) and menin-null (Men1-KO) mouse embryonic stem cells (mESCs), respectively, or 3T3-L1 cells without or with menin knockdown to investigate cell size, lipid content, and gene expression changes. Adipocytes derived from Men1-KO mESCs or after menin knockdown in 3T3-L1 cells showed a 1.5–1.7-fold increase in fat-cell size. Global gene expression analysis of mESC-derived adipocytes showed that lack of menin downregulated the expression of many differentially methylated genes including the tumor suppressor long noncoding RNA Meg3 but upregulated gene expression from the prolactin gene family locus. Our results show that menin deficiency leads to fat-cell hypertrophy and provide model systems that could be used to study the regulation of fat-cell size.
PMCID: PMC4503551  PMID: 26229531
2.  Isolated Subclinical Hyperthyrotropinemia in Obese Children: Does Levothyroxine (LT4) Improve Weight Reduction during Combined Behavioral Therapy? 
Objective. The study aim was to analyze whether anthropometrical parameters and TSH values in obese children with isolated subclinical hypothyroidism (IsHT) treated with levothyroxine (LT4) and weight reduction program differ from those managed by dietary and behavior counselling only. Material and Methods. 51 obese children with IsHT, who were treated according to the same weight reduction program, were retrospectively analyzed. They were divided into two groups: Group 1, n = 26, and Group 2, n = 25, without or with LT4 therapy, respectively. Changes in anthropometrical (delta BMI z-score) and hormonal (delta TSH) status were analyzed at the first follow-up visit. Results. In both groups significant decrease of TSH and BMI z-score values were noted. TSH normalized in 80.9% of children from Group 1 versus 90.5% from Group 2, p = NS. Delta BMI z-score was insignificantly higher in Group 1 compared to Group 2. Delta TSH was significantly related to initial TSH level in children treated by lifestyle intervention program only. Conclusions. In obese children with sHT dietary-behavioral management intervention contributed to reduction of body mass index, irrespective of levothyroxine use. This finding suggests that moderately elevated levels of TSH are a consequence rather than cause of overweight and pharmacological treatment should be avoided.
PMCID: PMC4503571
3.  Effect of Advanced Glycation End Products on Human Thyroglobulin's Antigenicity as Identified by the Use of Sera from Patients with Hashimoto's Thyroiditis and Gestational Diabetes Mellitus 
Advanced glycation end products (AGEs) are formed on proteins after exposure to high concentrations of glucose and modify protein's immunogenicity. Herein, we investigated whether the modification of thyroglobulin (Tg) by AGEs influences its antigenicity and immunogenicity. Human Tg was incubated in vitro with increasing concentrations of D-glucose-6-phosphate in order to produce Tgs with different AGE content (AGE-Tg). Native Tg and AGE-Tgs were used in ELISA to assess the serum antibody reactivity of two patient groups, pregnant women with gestational diabetes (GDM), and patients with Hashimoto's thyroiditis (HT). We produced in vitro AGE-Tg with low and high AGE content, 13 and 49 AGE units/mg Tg, respectively. All HT patients' sera presented the same antibody reactivity profile against native Tg and AGE-Tgs, indicating that the modification of Tg by AGEs did not alter its antigenicity. Similarly, the GDM patients' sera did not discriminate among the two forms of Tg, native or artificially glycated, suggesting that the modification of Tg by AGEs might not alter its immunogenicity. The modification of Tg by AGEs has no obvious effect on neither its antigenicity nor, most likely, its immunogenicity. It seems that other Tg modifications might account for the production of aTgAbs in patients with GDM.
PMCID: PMC4503572  PMID: 26229534
4.  Role of Vitamin D in Osteoarthritis: Molecular, Cellular, and Clinical Perspectives 
Osteoarthritis is a debilitating and degenerative disease which affects millions of people worldwide. The causes and mechanisms of osteoarthritis remain to be fully understood. Vitamin D has been hypothesised to play essential roles in a number of diseases including osteoarthritis. Many cell types within osteoarthritic joints appear to experience negative effects often at increased sensitivity to vitamin D. These findings contrast clinical research which has identified vitamin D deficiency to have a worryingly high prevalence among osteoarthritis patients. Randomised-controlled trial is considered to be the most rigorous way of determining the effects of vitamin D supplementation on the development of osteoarthritis. Studies into the effects of low vitamin D levels on pain and joint function have to date yielded controversial results. Due to the apparent conflicting effects of vitamin D in knee osteoarthritis, further research is required to fully elucidate its role in the development and progression of the disease as well as assess the efficacy and safety of vitamin D supplementation as a therapeutic strategy.
PMCID: PMC4503574
5.  Efficacy of Subantimicrobial Dose Doxycycline for Moderate-to-Severe and Active Graves' Orbitopathy 
Aim. To study the efficacy and safety of subantimicrobial dose (SD) doxycycline(50 mg/d) in patients with active and moderate-to-severe Graves' orbitopathy (GO). Methods. Thirteen patients with active and moderate-to-severe GO received once daily oral doxycycline (50 mg/d) for 12 wk. Treatment response at 24 wk was used as the primary outcome, measured by a composite of improvement in Clinical Activity Score (CAS), diplopia, motility, soft tissue swelling, proptosis, and eyelid aperture. Secondary outcome was the change of quality of life score (QoL, including visual functioning subscale and appearance subscale). Adverse events were also recorded. Results. Overall improvement was noted in eight out of 13 patients (61.5%, 95% CI 31.6%–86.1%). Both CAS and soft tissue swelling significantly ameliorated in eight patients at 24 wk. Five patients (38.5%) had improvement in ocular motility of ≥8 degrees. Eyelid aperture (46.2%) also decreased remarkably. For QoL, a significant improvement in appearance subscale (P = 0.008) was noted during the study, whereas no difference was observed in visual functioning subscale (P = 0.21). Two patients reported mild stomachache at 12 wk. Conclusions. SD doxycycline appears to be effective and safe for the treatment of active and moderate-to-severe GO. It might serve as a new promising therapeutic strategy for GO. This trial is registered with NCT01727973.
PMCID: PMC4499606  PMID: 26221138
6.  Thyroid Stimulating but Not Blocking Autoantibodies Are Highly Prevalent in Severe and Active Thyroid-Associated Orbitopathy: A Prospective Study 
The clinical utility of the functional TSH receptor autoantibodies was prospectively evaluated in patients with thyroid-associated orbitopathy (TAO). Ophthalmic, endocrine, and serological investigations were performed in 101 consecutive patients with severe and active TAO. Serum thyroid stimulating (TSAb) and blocking (TBAb) antibody levels were measured with two bioassays using cells that express a chimeric TSH receptor and CRE-dependent luciferase. TSAb results are expressed as percentage of specimen-to-reference ratio (SRR %). Blocking activity is defined as percent inhibition of luciferase expression relative to induction with bovine TSH alone. All 101 consecutively followed-up patients with severe and active TAO were TBAb negative. In contrast, 91 (90%) were TSAb positive of whom 90 had Graves' disease. Serum TSAb levels correlated with the diplopia score (P = 0.016), total severity eye score (P = 0.009), proptosis (P = 0.007), lid aperture (P = 0.003), upper lid retraction (P = 0.006), keratopathy (P = 0.04), and thyroid binding inhibiting immunoglobulins (TBII, P < 0.001) and negatively with the duration of TAO (P = 0.002). Median serum values of TSAb were SRR% 418 (range 28% to 795%). TSAb, not TBAb, are highly prevalent in severe/active TAO and serum TSAb levels correlate with clinical disease severity.
PMCID: PMC4499387  PMID: 26221139
7.  Results after En Bloc Lateral Wall Decompression Surgery with Orbital Fat Resection in 111 Patients with Graves' Orbitopathy 
Purpose. To evaluate the effect of en bloc lateral wall decompression with additional orbital fat resection in terms of exophthalmos reduction and complications. Methods. A retrospective, noncomparative case series study from 1999 to 2011 (chart review) in Graves' orbitopathy (GO) patients. The standardized surgical technique involved removal of the lateral orbital wall including the orbital rim via a lid crease approach combined with additional orbital fat resection. Exophthalmos, diplopia, retrobulbar pressure sensation, and complications were analyzed pre- and postoperatively. Results. A total of 111 patients (164 orbits) with follow-up >3 months were analysed. Mean exophthalmos reduction was 3.05mm and preoperative orbital pressure sensation resolved or improved in all patients. Visual acuity improved significantly in patients undergoing surgery for rehabilitative or vision threatening purposes. Preoperative diplopia improved in 10 patients (9.0%) but worsened in 5 patients (4.5%), necessitating surgical correction in 3 patients. There were no significant complications; however, one patient had slight hollowing of the temporalis muscle around the scar that did not necessitate revision, and another patient with a circumscribed retraction of the scar itself underwent surgical correction. Conclusions. The study confirms the efficiency of en bloc lateral wall decompression in GO in a large series of patients, highlighting the low risk of disturbance of binocular functions and of cosmetic blemish in the temporal midface region.
PMCID: PMC4499402  PMID: 26221142
8.  Predictors of the Dose-Effect Relationship regarding Unilateral Inferior Rectus Muscle Recession in Patients with Thyroid Eye Disease 
Purpose. To evaluate whether inferior rectus muscle (IRM) thickness, the degree of adipose change in the IRM, smoking status, and the previous history of orbital radiotherapy can predict the dose-effect relationship regarding unilateral IRM recession in thyroid eye disease (TED). Methods. Twenty-five patients were retrospectively reviewed. We calculated the largest IRM cross-sectional area and evaluated the degree of adipose change in the IRM using magnetic resonance imaging. The degree of adipose change and smoking status were classified using grading scales (0–3); previous orbital radiotherapy was graded as 0 when a history was not available and 1 when it was available. The correlation between the dose-effect relationship and the hypothesized predictive factors was evaluated using stepwise multiple regression analysis. Results. The multiple regression model, with the exception of the history of the previous orbital radiotherapy, estimated a significant dose-effect relationship for the parameters evaluated (YDOSE-EFFECT = 0.013XIRM AREA  − 0.222XADIPOSE  − 0.102XSMOKING + 1.694; r = 0.668; adjusted r2 = 0.367; P = 0.005). Conclusions. The dose-effect relationship regarding unilateral IRM recession in TED could be predicted using IRM thickness, degree of intramuscular adipose change, and smoking status but could not be predicted using the previous orbital radiotherapy history.
PMCID: PMC4499406  PMID: 26221140
9.  Liver Dysfunction Associated with Intravenous Methylprednisolone Pulse Therapy in Patients with Graves' Orbitopathy 
Intravenous methylprednisolone (IVMP) pulse therapy is the first-line treatment for the active phase of moderate to severe Graves' orbitopathy (GO). However, acute and severe liver damage has been reported during and after IVMP therapy. In this retrospective study, we investigated risk factors for liver dysfunction during and after IVMP therapy based on 175 Japanese patients with moderate to severe GO and treated at our center between 2003 and 2011. The results showed that seven patients developed severe liver dysfunction with elevated serum alanine aminotransferase (ALT > 300 U/L). Mild (40–100 U/L) and moderate (100–300 U/L) increases of ALT occurred in 62 patients (35%) and 10 patients (6%), respectively. Liver dysfunction was more frequently observed in males, in patients receiving high-dose methylprednisolone, and patients aged over 50 years. Preexistent viral hepatitis was significantly associated with liver dysfunction (65% in patients positive for hepatitis B core antibody and patients positive for hepatitis C virus antibodies). Our study confirmed the association of liver dysfunction with IVMP during and after treatment. It suggests that, in patients with GO, evaluation of preexisting risk factors—including viral hepatitis—and careful weekly monitoring of liver function during IVMP therapy and monthly thereafter for 12 months are warranted.
PMCID: PMC4499413  PMID: 26221141
10.  Cushing's Disease: The Relevance of a Combined Dexamethasone Desmopressin Test as a Component of Postoperative Hormonal Evaluation 
Background. The risk of Cushing's disease (CD) recurring may persist for years, even after initially successful surgery. Objective. To prospectively assess the relevance of a combined dexamethasone desmopressin test (CDDT) as a component of postoperative hormonal evaluation, including the dynamics of ACTH and cortisol concentrations. Material and Methods. We included 28 patients after TSS for CD. Eighteen months after surgery the standard hormonal evaluation was performed, followed by a CDDT. Results. Fifteen patients (53.6%) were in remission whereas in 13 subjects (46.4%) hypercortisolemia was confirmed. Positive results of CDDT were observed in 12 noncured patients (92.3%) and in one subject in remission (6.7%). Negative results were obtained in 12 patients with remission (80%) and in one noncured patient (7.7%). With 2 patients in CD remission (13.3%) the test results were inconclusive. We confirmed a high compatibility between CDDT and standard hormonal assessment results (κ = 0.846; P < 0.001). Significant differences in ACTH and cortisol levels at each CDDT time point between the two studied subgroups were shown. Conclusions. A negative CDDT result can be regarded as one of the factors indicative of CD remission during follow-up. Additionally, CDDT can help distinguish persistent hypercortisolemia from naturally recurring adrenal function after TSS.
PMCID: PMC4491586  PMID: 26185496
11.  Vitamin D Status and VDR Genotype in NF1 Patients: A Case-Control Study from Southern Brazil 
Neurofibromatosis type 1 (NF1) patients are more likely to have vitamin D deficiency when compared to the general population. This study aimed to determine the levels of 25-OH-vitamin D [25(OH)D] in individuals with NF1 and disease-unaffected controls and analyze FokI and BsmI VDR gene polymorphisms in a case and in a control group. Vitamin D levels were compared between a group of 45 NF1 patients from Southern Brazil and 45 healthy controls matched by sex, skin type, and age. Genotypic and allelic frequencies of VDR gene polymorphisms were obtained from the same NF1 patients and 150 healthy controls. 25(OH)D deficiency or insufficiency was not more frequent in NF1 patients than in controls (p = 0.074). We also did not observe an association between FokI and BsmI VDR gene polymorphisms and vitamin D levels in NF1 patients, suggesting that their deficient or insufficient biochemical phenotypes are not associated with these genetic variants. The differences between the groups in genotypic and allelic frequencies for FokI and BsmI VDR gene polymorphisms were small and did not reach statistical significance. These polymorphisms are in partial linkage disequilibrium and the haplotype frequencies also did not differ in a significant way between the two groups (p = 0.613).
PMCID: PMC4487339  PMID: 26161090
12.  Analysis of Circulating MicroRNAs In Vivo following Administration of Dexamethasone and Adrenocorticotropin 
Purpose. The interaction of hormones of the pituitary-adrenal axis and adrenal cortex-associated circulating microRNAs is mostly unknown. We have studied the effects of dexamethasone and adrenocorticotropin on the expression of five circulating microRNAs (hsa-miR-27a, hsa-miR-200b, hsa-miR-214, hsa-miR-483-5p, and hsa-miR-503) reported to be related to the adrenal cortex in plasma samples. Methods. Expression of microRNAs was studied in plasma samples of 10 individuals examined by 1 mg dexamethasone suppression test and another 10 individuals stimulated by 250 μg tetracosactide (adrenocorticotropin). Total RNA was isolated and microRNA expression was analyzed by real-time reverse transcription quantitative polymerase chain reaction normalized to cel-miR-39 as reference. Results. Only circulating hsa-miR-27a proved to be significantly modulated in vivo by hormonal treatments: its expression was upregulated by dexamethasone whereas it was suppressed by adrenocorticotropin. Secreted hsa-miR-27a was significantly induced by dexamethasone in vitro in NCI-H295R cells, as well. The expression of hsa-miR-483-5p proposed as diagnostic marker for adrenocortical malignancy was not affected by dexamethasone or tetracosactide administration. Conclusions. hsa-miR-27a expression is modulated by hormones of the hypothalamic-pituitary-adrenal axis both in vitro and in vivo. The biological relevance of hsa-miR-27a modulation by hormones is unclear, but the responsiveness of circulating microRNAs to hormones of the pituitary-adrenal axis is noteworthy.
PMCID: PMC4487905  PMID: 26161091
13.  Gender-Specific Effect of -102G>A Polymorphism in Insulin Induced Gene 2 on Obesity in Chinese Children 
Background. Insulin induced gene 2 (INSIG2) encodes a protein that has a biological effect on regulation of adipocyte metabolism and body weight. This study aimed to investigate the association of INSIG2 gene -102G>A polymorphism with obesity related phenotypes in Chinese children and test gender-specific effects. Methods. The 2,030 independent individuals aged from 7 to 18 years, including 705 obese cases and 1,325 nonobese controls, were recruited from local schools. We measured the obesity-related phenotypes and detected the serum lipids. We genotype -102G>A polymorphism by using the matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Results. In all individuals, we found that the GG/GA genotype of INSIG2 -102G>A polymorphism was associated with risk of severe obesity (OR = 1.62, 95% CI: 1.11–2.36, and P = 0.012) under the dominant model. The association with severe obesity existed only in boys (OR = 1.91, 95% CI: 1.15–3.17, P = 0.012). The GG/GA genotype of -102G>A polymorphism was also associated with higher waist circumference (β = 2.61 cm, P = 0.031) in boys. No similar association was found in girls. The polymorphism was not associated with other obesity-related phenotypes, neither in all individuals nor in gender-specific population. Conclusions. This study identified a gender-specific effect of INSIG2 -102G>A polymorphism on risk of severe obesity and waist circumference in Chinese boys.
PMCID: PMC4487926  PMID: 26161092
14.  Hypothyroidism Affects Vascularization and Promotes Immune Cells Infiltration into Pancreatic Islets of Female Rabbits 
Thyroidectomy induces pancreatic edema and immune cells infiltration similarly to that observed in pancreatitis. In spite of the controverted effects of hypothyroidism on serum glucose and insulin concentrations, the number and proliferation of Langerhans islet cells as well as the presence of extracellular matrix are affected depending on the islet size. In this study, we evaluated the effect of methimazole-induced hypothyroidism on the vascularization and immune cells infiltration into islets. A general observation of pancreas was also done. Twelve Chinchilla-breed female adult rabbits were divided into control (n = 6) and hypothyroid groups (n = 6, methimazole, 0.02% in drinking water for 30 days). After the treatment, rabbits were sacrificed and their pancreas was excised, histologically processed, and stained with Periodic Acid-Schiff (PAS) or Masson's Trichrome techniques. Islets were arbitrarily classified into large, medium, and small ones. The external and internal portions of each islet were also identified. Student-t-test and Mann-Whitney-U test or two-way ANOVAs were used to compare variables between groups. In comparison with control rabbits, hypothyroidism induced a strong infiltration of immune cells and a major presence of collagen and proteoglycans in the interlobular septa. Large islets showed a high vascularization and immune cells infiltration. The present results show that hypothyroidism induces pancreatitis and insulitis.
PMCID: PMC4484561  PMID: 26175757
15.  Leptin as well as Free Leptin Receptor Is Associated with Polycystic Ovary Syndrome in Young Women 
Background and Aim. Leptin has two forms in the circulation: free and bound forms. The soluble leptin receptor (sOB-R) circulates in the blood and can bind to leptin. The aim of this study is to assess the concentrations of the leptin and the sOB-R in PCOS and its relation to adiposity, insulin resistance, and androgens. Methods. A cross-sectional study included 78 female students aged 17–25 years. Fasting serum leptin and sOB-R concentrations were measured. The anthropometric variables and the hormonal profile such as insulin, female and male sex hormones, and prolactin were assessed. Results. In PCOS, leptin level (ng/ml) and free leptin index (FLI) increased significantly while sOB-R (ng/ml) significantly decreased compared to control subjects. In age-matched subjects, obese PCOS had increased leptin level in ng/ml (median level with interquartile levels) of 45.67 (41.98–48.04) and decreased sOB-R in ng/ml 11.47 (7.59–16.44) compared to lean PCOS 16.97 (10.60–45.55) for leptin and 16.62 (11.61–17.96) for sOB-R with p values 0.013 and 0.042, respectively. However, body mass index (BMI) is significantly correlated with leptin and s-OBR, while no significant correlations with parameters of insulin resistance were detected. Conclusion. PCOS is associated with hyperleptinemia and increased free leptin index. Decreased sOB-R could be a compensatory mechanism for the defective action of leptin.
PMCID: PMC4477211  PMID: 26180527
16.  Changes in Serum TSH and T4 Levels after Switching the Levothyroxine Administration Time from before Breakfast to before Dinner 
Background. Levothyroxine is commonly used in the treatment of patients with hypothyroidism. Levothyroxine is most often administered in the morning, on an empty stomach, in order to increase its oral absorption. However, many patients have difficulties taking levothyroxine in the morning. Aim. The aim of this study was evaluating the effect of changing levothyroxine administration time from before breakfast to before dinner on the serum levels of TSH and T4. Subjects and Methods. Fifty patients between 18 and 75 years old with hypothyroidism were included in the study and were randomly divided into two groups. Each group received two tablets per day (one levothyroxine tablet and one placebo tablet) 30 minutes before breakfast and 1 hour before dinner. After two months, the administration time for the tablets was changed for each group, and the new schedule was continued for a further two-month period. The serum TSH and T4 levels were measured before and after treatment in each group. Results. Changing the levothyroxine administration time resulted in 1.47 ± 0.51 µIU/mL increase in TSH level (p = 0.001) and 0.35 ± 1.05 µg/dL decrease in T4 level (p = 0.3). Conclusions. Changing the levothyroxine administration time from before breakfast to before dinner reduced the therapeutic efficacy of levothyroxine.
PMCID: PMC4475535  PMID: 26136778
17.  Shear Wave Velocity: A New Quantitative Index to Estimate the Status of Thyroid in Diffuse Thyroid Disease 
Objective. The purpose of the study was to assess the application value of VTQ in DTD. Research Design and Methods. Thirty healthy subjects and 74 DTD patients were involved. The thyroid stiffness, which was expressed by SWV, was measured by VTQ and compared between the patients and healthy people. The relationship between SWV and thyroid serological indexes was also analyzed. Results. The thyroid SWVs of DTD patients were higher than those of the healthy (2.56 ± 1.33 m/s versus 1.74 ± 0.16 m/s, P = 0.011). There was no significant difference between the thyroid SWVs in GD and HT patients (P = 0.168). The SWVs in patients with GD and HT were both higher than those of the healthy (P < 0.05). The area under the ROC curve was 0.938 for SWV to distinguish between DTD and healthy thyroid. With a cutoff value of 2.02 m/s, the sensitivity and specificity were 81.12% and 100.00%, respectively. Additionally, we found a positive liner correlation between thyroid SWV and TSH in DTD patients (P < 0.001). Conclusion. SWV is a good indicator of the thyroid tissue stiffness, which might be considered helpful in screening DTD. What is more, SWV might have a potential in assessing the thyroid function.
PMCID: PMC4469789  PMID: 26146499
18.  Mechanisms Linking Inflammation to Insulin Resistance 
Obesity is now widespread around the world. Obesity-associated chronic low-grade inflammation is responsible for the decrease of insulin sensitivity, which makes obesity a major risk factor for insulin resistance and related diseases such as type 2 diabetes mellitus and metabolic syndromes. The state of low-grade inflammation is caused by overnutrition which leads to lipid accumulation in adipocytes. Obesity might increase the expression of some inflammatory cytokines and activate several signaling pathways, both of which are involved in the pathogenesis of insulin resistance by interfering with insulin signaling and action. It has been suggested that specific factors and signaling pathways are often correlated with each other; therefore, both of the fluctuation of cytokines and the status of relevant signaling pathways should be considered during studies analyzing inflammation-related insulin resistance. In this paper, we discuss how these factors and signaling pathways contribute to insulin resistance and the therapeutic promise targeting inflammation in insulin resistance based on the latest experimental studies.
PMCID: PMC4468292  PMID: 26136779
20.  The Prevalence and Associated Risk Factors of Impaired Glucose Regulation in Chinese Adults: A Population-Based Cross-Sectional Study 
The goal of this study was to determine the prevalence and associated risk factors of impaired glucose regulation (IGR) in the population of Tongzhou, China, and to provide scientific basis for preventive interventions. In the study, the overall age-standardized prevalence of IGR (16.0%) in Tongzhou residents was higher than that in the national population (15.0%). There was no significant geographic difference in prevalence of IGR between urban and rural males. Older age, elevated blood pressure, high serum lipids, overweight, and central obesity were significantly associated with increased risk of IGR.
PMCID: PMC4468349  PMID: 26136780
21.  The Effect of Long-Term Intranasal Serotonin Treatment on Metabolic Parameters and Hormonal Signaling in Rats with High-Fat Diet/Low-Dose Streptozotocin-Induced Type 2 Diabetes 
In the last years the treatment of type 2 diabetes mellitus (DM2) was carried out using regulators of the brain signaling systems. In DM2 the level of the brain serotonin is reduced. So far, the effect of the increase of the brain serotonin level on DM2-induced metabolic and hormonal abnormalities has been studied scarcely. The present work was undertaken with the aim of filling this gap. DM2 was induced in male rats by 150-day high-fat diet and the treatment with low dose of streptozotocin (25 mg/kg) on the 70th day of experiment. From the 90th day, diabetic rats received for two months intranasal serotonin (IS) at a daily dose of 20 μg/rat. The IS treatment of diabetic rats decreased the body weight, and improved glucose tolerance, insulin-induced glucose utilization, and lipid metabolism. Besides, it restored hormonal regulation of adenylyl cyclase (AC) activity in the hypothalamus and normalized AC stimulation by β-adrenergic agonists in the myocardium. In nondiabetic rats the same treatment induced metabolic and hormonal alterations, some of which were similar to those in DM2 but expressed to a lesser extent. In conclusion, the elevation of the brain serotonin level may be regarded as an effective approach to treat DM2 and its complications.
PMCID: PMC4466391  PMID: 26124826
22.  Optimizing Bone Health in Duchenne Muscular Dystrophy 
Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder characterized by progressive muscle weakness, with eventual loss of ambulation and premature death. The approved therapy with corticosteroids improves muscle strength, prolongs ambulation, and maintains pulmonary function. However, the osteoporotic impact of chronic corticosteroid use further impairs the underlying reduced bone mass seen in DMD, leading to increased fragility fractures of long bones and vertebrae. These serious sequelae adversely affect quality of life and can impact survival. The current clinical issues relating to bone health and bone health screening methods in DMD are presented in this review. Diagnostic studies, including biochemical markers of bone turnover and bone mineral density by dual energy X-ray absorptiometry (DXA), as well as spinal imaging using densitometric lateral spinal imaging, and treatment to optimize bone health in patients with DMD are discussed. Treatment with bisphosphonates offers a method to increase bone mass in these children; oral and intravenous bisphosphonates have been used successfully although treatment is typically reserved for children with fractures and/or bone pain with low bone mass by DXA.
PMCID: PMC4466394  PMID: 26124831
23.  Polycystic Ovary Syndrome: Important Underrecognised Cardiometabolic Risk Factor in Reproductive-Age Women 
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder amongst women of reproductive age. Although PCOS is diagnosed exclusively based on reproductive criteria, it is also a metabolic disorder. Insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, obesity, and dyslipidemia are more common in women with PCOS than in age-comparable women without PCOS. Many of the metabolic abnormalities that manifest in PCOS are worsened by the concurrent incidence of obesity. However, some of these metabolic perturbations occur even in lean women with PCOS and therefore are rightfully recognized as intrinsic to PCOS. The intrinsic factors that produce these metabolic disturbances are reviewed in this paper. The consequences of obesity and the other metabolic aberrations are also discussed. The metabolic perturbations in PCOS patients lead to chronic low-grade inflammation and to cardiovascular impairments that heighten the risk of having cardiovascular disease. Even though many studies have shown an elevation in surrogate biomarkers of cardiovascular disease in PCOS women, it is still not clear to what extent and magnitude the elevation precipitates more frequent and earlier events.
PMCID: PMC4466395  PMID: 26124830
24.  Adrenergic System Activation Mediates Changes in Cardiovascular and Psychomotoric Reactions in Young Individuals after Red Bull© Energy Drink Consumption 
Objectives. To assess the effect of Red Bull© on (1) blood glucose and catecholamine levels, (2) cardiovascular and respiratory function changes before, during, and after exercise, (3) reaction time, (4) cognitive functions, and (5) response to mental stress test and emotions in young healthy individuals (N=38). Methods. Heart rate (HR) and arterial blood pressure (ABP), blood glucose, adrenaline, and noradrenalin plasma levels were measured before and after Red Bull© intake. Participants were subjected to 4 different study protocols by randomized order, before and 30 minutes after consumption of 500 mL of Red Bull©. Results. Mean ABP and HR were significantly increased at rest after Red Bull© intake. Blood glucose level and plasma catecholamine levels significantly increased after Red Bull© consumption. Heart rate, respiration rate, and respiratory flow rate were significantly increased during exercise after Red Bull© consumption compared to control condition. Intake of Red Bull© significantly improved reaction time, performance in immediate memory test, verbal fluency, and subject's attention as well as performance in mental stress test. Conclusion. This study demonstrated that Red Bull© has beneficial effect on some cognitive functions and effect on cardiovascular and respiratory system at rest and during exercise by increasing activity of the sympathetic nervous system.
PMCID: PMC4466468  PMID: 26124829
25.  Coronary Microvascular Function and Beyond: The Crosstalk between Hormones, Cytokines, and Neurotransmitters 
Beyond its hemodynamic function, the heart also acts as a neuroendocrine and immunoregulatory organ. A dynamic communication between the heart and other organs takes place constantly to maintain cardiovascular homeostasis. The current understanding highlights the importance of the endocrine, immune, and nervous factors to fine-tune the crosstalk of the cardiovascular system with the entire body. Once disrupted, this complex interorgan communication may promote the onset and the progression of cardiovascular diseases. Thus, expanding our knowledge on how these factors influence the cardiovascular system can lead to novel therapeutic strategies to improve patient care. In the present paper, we review novel concepts on the role of endocrine, immune, and nervous factors in the modulation of microvascular coronary function.
PMCID: PMC4466475  PMID: 26124827

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