Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders) - Volume 17, Issue 3, 2017

Background and Objective: Chronic Arsenic (As) exposure continued to be a cause of major problem associated with different kind of diseases including skin problem and different types of cancer. As exposure leads to numerous other pathological conditions that affect millions of people worldwide on a regular basis. It was recently established that As toxicity affects immune system and modulates the function and survival of cells involved in immune regulation. Arsenic trioxide (As2O3) was reported to be an effective apoptosis inducer in a variety of cell types. Despite intensive research, the exact immune-modulatory role of As is poorly understood till now. Methods: We reviewed the immunological imbalance caused due to As exposure and focused on regulatory T cells (Tregs cells). In this review, we mainly focused on role of As and its potential mechanisms in the induction and modulation of Tregs cells. Conclusion: The multiple effects of As on immune system tend to decrease the immune surveillance system and increase the rate of infection, autoimmune disease, cancer and other immune mediated problems. As exposed individuals showed induction of oxidative stress, inflammation and impaired lymphocytes activation. The effect of As on T cell population is mainly attributed to altered expression of key immune regulator molecules impaired T cell functions, cytokines production, induction of apoptosis, and oxidative stress induction in T cells.

Background and Objective: Glycolytic activity during Crabtree effect is similar to that in tumor cells. Research regarding Crabtree effect is very much crucial. Methods: The mechanism of metabolic activities in glycolysis pathway and oxidative phosphorylation pathway in regards to Crabtree effect in Saccharomyces cerevisiae was studied in this paper. We also explored the effects of hexose phosphates in the activities of respiratory chain complexes (III and IV) in inhibition of respiration. Besides, the enhancement of fermentation in response to excess glucose concentration was studied. We discussed the significance of Crabtree effect in mammalian cancer in terms of Crabtree effect in a Crabtree positive organism, as it is similar to cancer metabolism in mammalian cells. We developed an in silico model of Crabtree effect. Results: A comparative study was performed with laboratory experiments regarding inhibitory role of fructose 1,6-bisphosphate on metabolic respiration. The model was simulated for different concentration levels of glucose and hexose phosphates using COPASI and SNOOPY tools. Conclusion: We have shown that a hike in glucose concentration increases ethanol concentration and leads glycolytic activity towards fermentation. This phenomenon occurs during Crabtree effect.

Background and Objective: Psoriasis is a chronic and complex autoimmune inflammatory skin disease that affects over 125 million people worldwide. It can exhibit at any age, in spite of the fact that children are less normally influenced than adults. It is characterized by distinct erythematous plaques shielded with conspicuous silvery scales that shows up in different areas of the skin. Knowledge of pathophysiology, especially the pathogenesis of psoriasis, has significantly progressed in the recent decade. Advancement in molecular knowledge leads to better understanding of the disease, thus influencing the development of efficient treatment modalities. However, even with the availability of various options of treatment most of the efficient treatment modalities are costly. Expenses of health care bring about major financial weight to the patients as well as to health care systems. Thus, it was important to review the available current treatment options and those which are under development, in terms of efficacy, safety and cost to assist in selecting the most appropriate treatment for psoriasis patients. Methods: Literatures were searched by using key words psoriasis, topical treatment, systemic treatment, biologics and phototherapies, on Embase, Medline, Jstor, Cochrane and Merck Index databases. Results: Life-style choices such as smoking, alcohol consumption, obesity and stress are recognised as risk factors and triggers associated with psoriasis. Psoriasis poses psycho-social and economic burden on affected patients that sometimes leads to depression, reduced social interaction and suicidal tendencies in patients. Depending on the type, severity and extent of the disease, comorbidities, patient preference, efficacy and safety profile, numerous treatment modalities and therapeutic agents are available such as topical, systemic, biologic and phototherapeutic treatments. However, it was found that among all the current available treatments for psoriasis, biologic agents and phototherapeutic modalities are the most commonly employed treatment modalities for moderate to severe psoriasis. Conclusion: Evaluation of present-day available treatment alternatives will surely help physician to select a suitable module for each patient while keeping in mind the financial status of the patient. Future research should aim to develop therapies which are efficient, safe and cost-effective.

Background and Objective: T-cadherin is a unique member of the cadherin family and is primarily expressed in the cardiovascular system. T-cadherin has not been abundantly studied, but the studies conducted to date have explored the impact of this protein on health and the function of organs involved in metabolic regulation. Methods: This article examines the recent knowledge of the ligand partners for T-cadherin and the potential contribution(s) of T-cadherin to cardio-metabolic function. Result and Discussion: One significant role for T-cadherin is its ability to bind high molecular weight adiponectin in cardiovascular tissue, thereby mediating the cardio-protective benefits of adiponectin. It also has the ability to bind low-density lipoprotein via its glycosylphosphatidylinositol anchor; however, the exact physiological consequence of this ligand-receptor relationship is not known. T-cadherin appears to affect multiple conditions of cardio-metabolic disease, including atherosclerosis and insulin resistance. Research into T-cadherin has suggested that it may be useful as a diagnostic marker for the early stages of cardiovascular disease. However, with regard to insulin, T-cadherin is necessary for pancreatic insulin secretion, but overexpression of T-cadherin on vascular cells may promote endothelial insulin resistance. Conclusion: This review provides evidence that T-cadherin has an influential role on key cardiometabolic molecules and warrants further investigation.

Background: It is generally accepted that serum osteocalcin (OC) is a reliable marker of bone formation, while the role of serum uric acid (UA) in bone metabolism is still debated. However, recent studies have shown that endogenous UA within the normal range may exert a positive effect in bone formation by means of its antioxidant role in both sexes. To date, no studies have been carried out in obese subjects aiming to study the relationship between serum OC and UA, given that obesity is considered as a risk factor for osteoporosis and fracture and, at the same time, for cardiovascular events. Objectives: Our search purpose was to verify the relationship between endogenous levels of OC and serum UA in a cohort of obese subjects without any metabolic or chronic diseases (i.e. hypertension, renal failure, diabetes mellitus, etc.). Materials and Methods: One hundred and twenty one obese subjects (93 women and 28 men) were enrolled for this study. Serum OC and UA were assessed and compared with demographic characteristics, clinical and biochemical parameters (age, body mass index (BMI), blood pressure, waist circumference, serum lipids and glycaemia). Results: Serum OC was directly and independently correlated with circulating UA in our population of obese subjects, while neither BMI, age, serum lipids, fasting glycaemia nor gender showed a statistically significant correlation with endogenous plasma levels of OC. Conclusion: The positive effect determined by serum OC in bone metabolism of our obese subjects might be partly due to the antioxidant properties that normal plasma UA levels exert at bone tissue level.

Background: Differentiated thyroid carcinomas (DTCs) account for about 1% of all human malignancies. Cervical lymph nodes metastases and recurrences in the thyroid bed frequently occur. Furthermore, ++about 10-15% of patients develop distant metastases. Therefore, patients must undergo life-long follow-up. Objective: The aim of this study was to evaluate the usefulness of Thyroglobulin measurement in FNAB washout (FNAB-Tg) in the detection of local metastasis in patients affected by or evaluated for thyroid cancer. Materials and Methods: In a 3-year period, a total of 83 consecutive patients coming to our attention at the Ear-Nose-Throat (ENT) Outpatients Service of the National Cancer Research Center "Istituto Tumori Giovanni Paolo II" of Bari, Italy, because of the finding of one or more cervical lymph node(s), were enrolled in the study. After collection of the cytological specimen, the needle used for performing FNAB was then washed in 1 ml of normal saline. 89 FNAB washouts were collected from the same number of lymph nodes and subsequently investigated for Thyroglobulin levels using a sequential chemiluminescent-immunometric assay. Results: Comparing the cytological or, when performed, histological diagnoses with the results of FNAB-Tg, we found that in 24 cases of lymph node metastases from PTC (19 lymph nodes from patients at the first diagnoses and 5 lymph nodes from PTC patients in follow up) the mean level of Thyroglobulin was 1840.11 ng/ml; range: <0,2 to 11440 ng/ml. In the group of PTC patients (27 lymph nodes) with lymph nodes negative for metastatic involvement at cytology (i.e. no lymph node recurrence at follow-up), as well as in the cases of subjects without PTC and submitted to FNAB because of the appearance of lymph node(s) classified as reactive at cytology (37 lymph nodes), FNAB-Tg was lower than or equal to 0.2 ng/ml. As expected, the Thyroglobulin level was not detectable (< 0.2 ng/ml) also in a lymph node FNAB from a case of anaplastic thyroid carcinoma. detectable in all node negative patients showing, when considering together all the lymph node m Conclusion: In our study, FNAB-Tg was notetastases, a 96% sensitivity and 100% specificity.

Objective: The present research explored the relationship of vitamin D status with prolactin levels and adenoma size in female patients with newly diagnosed prolactinoma and determination of hypovitaminosis D prevalence among female patients with prolactinoma. Patients and Methods: We enrolled 67 female patients with newly diagnosed prolactinoma (41 with micro adenoma and 26 with macro adenoma) in this case-control study at the time of presentation. We selected 45 female subjects as a control group who were matched according to age, weight, height, body mass index and waist circumference. We investigated 25-hydroxyvitamin D, the major circulating form of vitamin D. Results: Prolactinoma patients had significantly lower 25-hydroxyvitamin D levels in comparison with control subjects. Also, macroadenoma patients showed significantly lower 25-hydroxyvitamin D levels as compared to microadenomoa patients. By contrast, microadenoma patients had nonsignificant lower 25-hydroxyvitamin D levels in comparison with control subjects. Furthermore, we found prolactinoma patients with 25-hydroxyvitamin D >20.00 ng/ml showing significant differences in the prolactin levels and adenoma size when compared with those who had 25- hydroxyvitamin D <20.00 ng/ml. In regression analysis, 25-hydroxyvitamin D level was a significant predictor of adenoma size in patients diagnosed with prolactinoma. Conclusion: Female patients with prolactinoma have lower vitamin D levels and have higher prevalence of vitamin D insufficiency and deficiency among prolactinoma patients when compared with normal subjects. Also vitamin D deficiency in prolactinoma patients associated with larger adenoma size and higher prolactin level. Finally, 25-hydroxyvitamin D level was a statistically significant predictor of prolactinoma size but not prolactin levels.

Background and Aim: Current data show that 1h oral glucose tolerance test (OGTT) blood glucose (1h-BG) might identify persons at increased risk of developing type 2 diabetes and cardiovascular diseases more precisely than fasting blood glucose (FBG) and 2h OGTT blood glucose (2h-BG). The aim of study was to determine whether is justified to use 1h-BG over traditional blood glucose measurements, in cardiometabolic profiling of obese individuals. Method: Cross-sectional study enrolled 60 obese individuals without previous history of diabetes and other cardiometabolic disorders. Anthropometrical, ultrasound and laboratory examinations were conducted. Results: All three parameters significantly directly correlated with age, body mass index, waist circumference, erythrocyte sedimentation rate, C-reactive protein, triglycerides and glycated hemoglobin. FBG and 1h-BG significantly directly correlated with alanine transaminase, gammaglutamyltransferase and total cholesterol. FBG significantly directly correlated with fibrinogen and aspartate transaminase, 1h-BG with systolic blood pressure and 2h-BG with diastolic blood pressure. None of parameters significantly correlated with gender, total white blood cell count, uric acid, 25-hydroxyvitamin D, high density lipoprotein cholesterol, low density lipoprotein cholesterol, serum adiponectin and albuminuria. Differences in correlation coefficients were not statistically significant. Individuals with 1h-BG >8.6 mmol/l had much more proatherogenic cardiometabolic profile, as well as higher incidence of dysglycemia, metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD) than ones with 1h-BG <8.6 mmol/l, but all differences were driven by the average value of glycemia. There were no statistically significant differences in ability of predicting MetS, NAFLD and pathologically increased carotid artery intima media thickness among analyzed glucose metabolism parameters. Conclusion: 1h-BG is not superior to FBG and 2h-BG in the identification of proatherogenic cardiometabolic profile in obesity.

Background: Type 1 diabetes mellitus is described as a chronic metabolic disorder characterized by aggressive immune β-cell destruction. There are a number of varied immune mechanisms for sustaining self-tolerance in opposition to the autoimmune disorders. A recessive tolerance is accomplished by thymic gland via a negative assortment of different clones, while a dominant tolerance is accomplished by the regulatory T cells (Treg) in the periphery. Treg (CD4+ CD25+FOXP3+) are subsets of T cells which have an essential role in maintaining tolerance. Objective: To evaluate peripheral Treg (CD4+; CD25+; FOXP3+) in children cohort with T1DM. Methods: This study included 64 children diagnosed with T1DM and 35 age- and sex-matched healthy children as controls. All children were clinically evaluated and subjected to assessment of complete blood count (CBC), glycated hemoglobin, surface and cytoplasmic detection of Treg by flow cytometry. Results: This study showed that the frequency of Treg (CD4+; CD25+; FOXP3+) was significantly lower in diabetic children than with normal controls (P<0.001). There was a significant (P <0.001) reduction in the Treg (CD4+; CD25+; FOXP3+) in T1DM children with uncontrolled (Hemoglobin A1c>7%) as compared to those with controlled (Hemoglobin A1c<7%) disease. Conclusion: Diminished Treg in T1DM proved that auto-reactivation of T-cell as a result of the breakdown of immune tolerance takes part in the elaboration of autoimmune disorders as T1DM. Treg may be used in immunotherapy, thus preventing T1DM development due to its pivotal role in immune tolerance.

Background: Gestational diabetes mellitus (GDM) is a major health concern that seems to be influenced by seasonality. Objective: To assess the impact of seasonality on the incidence of GDM in an Italian population. Method: This is a retrospective cohort study of 5,473 pregnant women attending the Operative Unit of Diabetes, who underwent GDM screening by means of the 75-g oral glucose tolerance test (OGTT), during the period from August 2011 to December 2016. Screening was performed at 16-18 or 24-28 weeks' gestation, following the Health Italian Minister guidelines. All blood samples were undertaken in the Hospital itself, under the same temperature conditions, and analyzed in the nearby biochemical laboratory. Statistical analysis was performed by SPSS software. Results: 1,559 of 5,473 enrolled women (28.5%) were affected by GDM. The incidence of GDM was significantly higher during the summer season (33.7%) (P<0.001), and significantly lower during the winter (23.3%), compared with spring (P=0.035) and fall seasons (P=0.002). When the year was divided on a 24-hr temperature basis into two parts only, the warm half and the cold half, GDM was considerably lower in cold months compared to warm ones (P<0.0001). No difference was observed between the medians of fasting glycemia throughout the four seasons; instead, serum glucose levels at 1-h and 2-h after OGTT were higher in summer than in spring, autumn and winter. Results from multiple linear regression analysis supported the hypothesis that glucose levels at 1-h and 2-h following OGTT could be influenced by ambient temperature. Conclusion: Our data indicate that seasonal changes may influence variations in glucose tolerance during pregnancy, with GDM incidence increasing during the summer and declining during cold months.