Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders) - Volume 15, Issue 4, 2015

Weight gain and metabolic disturbances are common side effects during psychopharmacological treatment with specific antipsychotics and antidepressants. The antipsychotics clozapine and olanzapine, and antidepressants tricyclics and mirtazapine have a high risk of inducing weight gain. Recently discovered pathophysiological mechanisms include antihistaminergic effects, activation of hypothalamic adenosine monophosphate-activated protein kinase (AMPK), modulation of hormonal signaling of ghrelin and leptin, changes in the production of cytokines such as tumor necrosis factor-alpha (TNF)-alpha and adipokines such as adiponektin, and the impact of genes, in particular the melanocortin 4 receptor (MC4R), serotonin 2C receptor (HTR2C), leptin, neuropeptide Y (NPY) and cannabinoid receptor 1 (CNR1) genes. Metabolic changes associated with weight gain include disturbances of glucose and lipid metabolism. Clozapine and olanzapine may, in addition to mechanisms resulting from weight gain, impair glucose metabolism by blockade of the muscarinic M3 receptor (M3R). Antidepressants associated with weight gain appear to have fewer unfavourable effects on glucose and lipid metabolism than the second-generation antipsychotics clozapine and olanzapine. To assess the risk of weight gain and its consequences for the patient’s health, assessing body weight changes and metabolic monitoring in the first week of treatment as well as in long-term treatment is recommended.

Common risk markers for periodontitis and prevalent systemic comorbidities indicate similarities in their progression and molecular mechanisms involved. Resultant pro-oxidant disease profiles provide scope for attenuating their pathogeneses with appropriate adjunctive antioxidants. Levels of oxidative stress markers 8-hydroxy-deoxguanosine (8-HOdG) and malondialdehyde (MDA) are significantly higher in periodontitis and other chronic inflammatory conditions. There is a clear link between periodontitis and diseases associated with significant systemic inflammatory loading, such as metabolic syndrome. Micro- and macro-nutrients have proven to be effective in curbing molecular mechanisms that generate reactive oxygen and nitrogen species. A Mediterranean diet rich in fruits, vegetables, legumes, whole grain, nuts, fish, olive oil and red wine in moderation, could be attributed to the lower occurrence of cardiovascular disease, insulin resistance and other inflammatory diseases in this region. A significant number of naturally occurring flavonoids have been identified in these products. Flavonoids comprising flavonols, flavones and isoflavones are potent free radical scavengers, effective in inhibiting lipid peroxidation, with anti-atherosclerotic and antihypertensive effects.The phenolic compound oleocanthal isolated in virgin olive oil has similar anti-inflammatory actions to that of ibuprofen. The anti-atherogenic effects of MUFA and PUFA in nuts, enhance endothelial function by reducing total cholesterol, oxidized LDL, hs-CRP, sVCAM-1 levels, lipids, lipoproteins and inflammatory markers. Epigenetics influenced by environmental factors and interactions between genes and nutrients, are important considerations in influencing these effects. Using antioxidants as therapeutic adjuncts could enhance the antioxidant capacity of an inherent glutathione system and overcome oxidative effects, thereby mitigating therapeutic side-effects.

Vitamin D and its active form 1α,25(OH)2D3 has been recently indicated to have a fundamental role in immune regulation. An interplay between gut and white adipose tissue (WAT), mainly mediated by enterogastric hormones and adipokines, such as leptin, adiponectin and ghrelin, actively participate in the immune homeostasis and modulation both of the innate/acquired immune response and between T-cell effector/T-cell regulatory skewing. Particularly for leptin, this action promotes and enhances immune tolerance at the gut level and pro-inflammatory effect at WAT level, while calcitriol participates in promoting and increasing an M2 macrophage-like skewing, a T-reg activity at WAT level and a iNKT function at gut level. The role of active vitamin D3 therefore is fundamental in the immune homeostasis of the WAT immune microenvironment and to support the role of WAT as an endocrine, tolerogenic organ.

Selenium and iodine are essential for thyroid hormone synthesis and function. Selenium, in form of selenocysteine, is found either in the catalytic center of enzymes involved in the protection of the thyroid gland from free radicals originating during thyroid hormone synthesis, and in three different iodothyronine deiodinases catalyzing the activation and the inactivation of thyroid hormones. Iodine is an essential constituent of thyroid hormones and its deficiency causes different disorders that include goiter, hypothyroidism, reduced fertility and alteration in growth, physical and neurological development. These two micronutrients could be involved in the pathogenesis of autoimmune thyroid diseases, a spectrum of pathological conditions including Hashimoto’s thryoiditis, post-partum thyroiditis, the so-called painless thyroiditis, Graves’ disease and Graves’ ophtalmopathy. Aim of this paper is to review the role played by selenium and iodine in autoimmune thyroiditis.

Spasticity is a motor disorder with an increased muscle tone, typically associated with spasms, weakness and lack of coordination. It is an invalidating and debilitating pathology, characterized by pain, limited autonomy in activities of daily living, development of severe lesions. Spasticity can be adequately treated with physiotherapy, muscle relaxants drugs or topical treatment with botulinic toxin type A. Intrathecal baclofen therapy is very effective in the treatment of severe and generalized spasticity. Sometimes, soft tissues adjacent to the implant intrathecal infusion become infected; removing intrathecal infusion and systemic antibiotic therapy are best solution for clinical cure. However, removing intrathecal baclofen therapy could increase muscle spasticity with enhancement of pain and clonus that can worsen quality of life. In this study, we evaluated clinical improvement after complete healing of the septic focus and implantation of a new infuser.

Hypertensive patients are at higher risk of pre-diabetes (impaired fasting glucose IFG and impaired glucose tolerance IGT) and type 2 DM. This study was done to examine whether some general, anthropometric, hormone, and metabolic parameters are different between subjects with normal and impaired glucose metabolism (IGM) in hypertensive subjects, thus possibly identifying some variable characterizing glucose metabolism derangement in these patients. A cohort of 134 hypertensive patients, 55 women and 79 men, aged 37-70 years, were examined. IGM patients were considered those showing IFG and/or IGT or type 2 DM after an oral glucose tolerance test (OGTT), and/or HbA1c > 48 mmol/l (6.5%) and/or glucose levels >155 mg/dL after 1 hour of the OGTT. Body mass index (BMI), waist circumference, and fasting insulin, TSH, FT3, FT4, glucose, and lipid (cholesterol, HDL-cholesterol and triglycerides) plasma concentrations were measured. Insulin resistance was also assessed by the homeostasis model assessment (HOMAIR). Results: Waist circumference (p < 0.05), fasting glucose (p < 0.05) and insulin levels (p < 0.05) and HOMAIR (p < 0.05) were significantly higher in patients with IGM than in control group. All other investigated parameters, as well as the number of antihypertensive drugs per single patient, were not different between the two groups. Conclusions: The present study, performed in a selected population of hypertensive subjects, shows that derangement of glucose metabolism is associated to central fat accumulation, hyperinsulinemia and insulin resistance

In the last decades, there have been many reports of HIV infection and abnormalities in lipid metabolism and cardiovascular disease (CVD). This study aims at describing the nutritional status of HIV-infected adults and its relation to lipid profile through traditional [total cholesterol (TC), HDL cholesterol (HDL), triglycerides (TG), non-HDL cholesterol and LDL cholesterol (LDL)] and other parameters [Apolipoprotein B (ApoB), fibrinogen, and high sensitive-C-reactive protein (hs-CRP)]. A cross-sectional descriptive study was performed. Body mass index (BMI) was calculated and references were taken from WHO. TC, HDL, TG and glucose were determined and non-HDL cholesterol and LDL were calculated. ApoB and fibrinogen were determined by quantitative radial immunodiffusion on agar plates (Diffuplate,Biocientífica SA,Argentina) and hs-CRP by immunoturbidimetric test. Qualitative variables were compared with the Chi-square test or Fisher's exact test. Quantitative variables were compared applying parametrics or nonparametric tests. Pearson test for correlations. Software SPSS 17.0. 97 patients were analyzed: 69.1% were men. 80% were on antiretroviral treatment. Average (SD) BMI was 24.3 (4.1) kg/m2. 29.4% were overweight and 5.9% obese. Patients with a BMI ≥25.0 kg/m2 presented significantly higher levels of TG, ApoB and glycemia than well-nourished people [246.1(169.0) vs. 142.9(78.4) mg/dL;p=0.029, 198.6(69.3) vs. 126.4(50.6) mg/dL;p=0.01 and 100 (3.2) vs. 90.2 (6.9) mg/dL;p=0.008 resp.] and a significantly decreased HDL [37.2(1.5) vs. 49.8(10.4) mg/dL;p<0.01]. No statistically significant correlation was found between ApoB and non-HDL (p=0,063). There was no evidence that there is a direct relation between Apo B and the other lipid parameters. The potential increase in CVD in this group of patients, would be related to the higher levels of TG, ApoB and overweight/obesity. Nutritional education is needed to promote a healthy weight to warn against the risk of cardiovascular disease.

Extensive exercise induces inflammatory reactions together with high production of free radicals and subsequent liver and kidney tissues damage. This study was designed to investigate for effects of melatonin on liver and kidney tissues in the extensive exercise exposed rats and non-exercised rats. In this research, 24-male Sprague-Dawley rats were divided into four groups. For exercise rat model, the rats were exposed to slow pace running with the velocity of 10 m/min for 5 minutes for five days just before the study. And for last ten days after adaptation period, the exercise was improved as 15 min with the speed of 20 m/min and intra-peritoneal melatonin injection has been performed to the melatonin treated groups with the dose of 10 mg/kg. Biochemical results revealed a decrease in the parameters of kidney and liver enzymes in exercise-group and an increase in the parameters of serum, liver and kidney enzymes in the group that melatonin-exercise-group. As for histological analysis, while it is observed that there are cellular degenerations in the liver and kidney tissues with exercise application, a decrease has been observed in these degenerations in the group that melatonin was applied. At the end of the research, it has been determined that exercise application causes some damages on liver and kidney, and these damages were ameliorated with melatonin treatment.

We reported a conversion assay in which thyroid blocking antibody (TBAb) function as thyroid stimulating antibody (TSAb). TBAb-bound porcine thyroid cells (PTC) were made by incubating TBAb(+) serum and PTC for 1 hour. When these TBAb-bound PTC were incubated 4 h with rabbit anti-human (h) IgG antibody (Ab), cAMP production was high, but when incubated with normal rabbit serum (NRS) cAMP production was low. TBAb-Mnoclonal Ab (MoAb) (KI-70) showed similar conversion. However, when TSAb-MoAb(M22) was assayed, anti-hIgG Ab-produced cAMP was lower than NRS-produced cAMP. When a mixture of M22 and KI-70 was assayed, anti-hIgG Ab-produced cAMP was higher than NRS. Thus, it is possible to determine existence of TBAb in TSAb(+)serum when anti-IgG Ab-produced cAMP is higher than NRS-produced cAMP. In this assay TBAb activity in TSAb(+)serum was scored as positive, gray zone and negative when the difference [anti-hIgG Ab-produced cAMP(%)128;•NRS-produced cAMP(%)] was >100%, 50-100% and <±50%, respectively. In TSAb(+)sera of Graves’ patients with no treatment or anti-thyroid therapy, positive TBAb was 9% (3/33 )and 6.9% (5/72), and gray zone was 18 % (6/33) and 25% (18/72), respectively. A low prevelance of TBAb and low TBAb activity (<200% as cAMP) was found in these Graves’ patients. A radioisotope treated Graves’ patient showed existence of both TSAb and TBAb at 5 months (NRS, 800% cAMP and anti-IgGAb,1,350% cAMP), and highly positive TBAb (NRS, 180% cAMP and anti-hIgG Ab, 3,200% cAMP) at 30 months. This conversion assay is useful principally for TBAb determination but is also useful for TBAb determination in TSAb(+)serum.

Background:- Steroid resistant nephrotic syndrome (SRNS) has a chronic and progressive course. Limited data is available evaluating thyroid function parameters in SRNS patients. The aim of the present study was to evaluate the thyroid hormone status in Indian children with SRNS. Materials & Methods: - The present cross-sectional study included 50 patients aged 1-12 years with SRNS. As per Up:Uc ratio divided into three groups: Group A) 16 patients of SRNS in complete remission Group B) 14 patients of SRNS in partial remission Group C) 20 patients of SRNS in relapse. Serum levels of FT3, FT4 and TSH were measured in all. Results:- 20% of the children (n=10) with SRNS had hypothyroidism (7 subclinical hypothyroidism and 3 with overt hypothyroidism). One child was found to be in complete remission, 4 in partial remission and 5 in relapse phase. TSH levels were found to be significantly elevated in children with relapse (p = 0.042). Serum albumin showed a significant negative correlation with Up:Uc ratio ( p < 0.0001) whereas total cholesterol showed a significant positive correlation (p < 0.001). On correlating TSH level with Up:Uc ratio a significant positive correlation ( p = 0.0098) was observed. Conclusion:- Subclinical hypothyroidism in SRNS is temporary and may improve with remission. However prolonged proteinuria in SRNS patients may lead to progressive damage of the renal tubules and impaired absorption of Low Molecular Weight (LMW) proteins which may further exhaust the thyroid reserve and lead to overt hypothyroidism. Therefore thyroid examination should be routinely advocated in these children.