Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders) - Volume 14, Issue 3, 2014

Obesity is associated with an oxidative stress status, defined as an excessive production of reactive oxygen species (ROS) compared to the level of antioxidants acting in the natural defence systems. Several sources of ROS can be identified in obesity (e.g., mitochondrial respiratory chain, or NADPH oxidase) and could contribute to the pathogenesis of obesity. Indeed, these conditions favour the development of insulin resistance and metabolic syndrome through deregulation of adipokines and pro-inflammatory cytokines, so that it could be of interest to associate antioxidant therapeutic strategies with strategies of weight loss. Among antioxidants, melatonin holds a special place, on the one hand for its antioxidant and anti-inflammatory properties, and on the other hand for its role as a metabolic regulator. As melatonin modulates several processes involved in obesity and its related metabolic alterations, it could have a therapeutic interest in the treatment of obesity.

Acromegaly is a chronic systemic disorder caused by a GH-secreting pituitary adenoma. Active acromegaly results in a poor quality of life due to symptoms such as headache, fatigue, arthralgia, depression, sexual dysfunction and hyperhidrosis; an increased prevalence of co-morbidities like diabetes, hypertension as well as cancer risk and a reduced life expectancy. Appropriate, modern, multimodal treatment of acromegaly has led to a significant improvement in quality of life, an adequate control of co-morbidities and a drastic reduction in the mortality rates that used to prevail in the past. This multimodal strategy includes an adequate selection of patients who are likely to benefit from surgical treatment (which has to be performed by a skilled pituitary neurosurgeon), the use of pharmacological interventions such as somatostatin analogs and dopamine agonists, which target the pituitary adenoma; and pegvisomant, a GH mutant acting as a competitive antagonist of the GH receptor. Radiation therapy is an important tool, particularly in parts of the World where resources are limited. The ultimate outcome of the individual patient depends on the judicious use of all these treatment options, which are critically analyzed in this mini-review.

We investigated whether there was a significant increase in thyroid autoimmunity, and disorders in patients with rheumatic diseases (RDs). We enrolled 201 patients with RDs (41 with ankylosing spondylitis, 15 with systemic lupus erythematosus, 80 with rheumatoid arthritis [RA], 65 with familial Mediterranean fever), and 122 healthy controls. Serum levels of thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), C-reactive protein, and thyroid autoantibodies (anti-thyroglobulin and anti-thyroid peroxidase) were measured in all participants. There were no significant differences between the ages of the patients and controls. The mean TSH values of the patients with RDs and the controls were 3.1±2.68mIU/L and 1.9±0.83mIU/L, respectively (P = 0.004). The mean fT4 value of the patients with RDs was 1.43±0.67ng/dL whereas that of the controls was 1.58±0.68ng/dL (P <0.001). Subclinical hypothyroidism was detected in 24 patients with RDs. Thyroid antibodies were detected in 16 of 201 (8%) patients with RDs. Three of these patients had subclinical hypothyroidism, while the others were euthyroid. Thyroid autoantibodies were significantly higher in patients with RDs (P <0.001). Additionally, thyroid disorders were observed more frequently in patients with RDs than in the healthy controls. Based on our findings, we recommend that thyroid function tests should better be included in the clinical evaluation of patients with RDs.

Asthma and obesity are two common disorders often associated in children and characterized by an inflammatory status. Growing evidences support a connection between obesity and asthma since weight reduction can improve asthmatic symptoms. In this study, we have enrolled eighty children: 17 non asthmatics and non obese, 19 obese, 28 asthmatics-obese and, 16 asthmatics non-obese, respectively. In all participants, respiratory functional tests and body mass index (BMI) were calculated. Moreover, systemic inflammation of biomarkers such as T helper (h)1-type, Th2-type and T regulatory-type serum cytokines along with major adipokines was determined. Data will show that the association between asthma and obesity leads to a predominant Th1-type response with an increase in pro-inflammatory cytokines. This inflammatory profile in asthmatics-obese children is sustained by elevated serum levels of leptin and visfatin, while adiponectin concentration is rather diminished. Finally, levels of systemic inflammatory biomarkers positively correlate with the increase in BMI values in all population subgroups.

This paper reviews puerperal metritis in the cow, particularly the complex and multi-factorial pathogenesis characterized by an altered cross-talk among infectious agents, endocrine and immune systems. Uterine infections impair fertility and is one of the main causes of economic losses in dairy production. The early postpartum is a period characterized by an increased exposition to infectious agents and the disruption of the metabolic homeostasis, leading to endocrine and immunologic disorders. Dysregulation of uterine defence mechanisms results in the development of metritis. Because there is a complex interaction between infectious, endocrine and immune factors during metritis, there is need to use safer and cheaper drugs which are able to strengthen the anti-infective actions of the routine therapies.

We report the case of a young woman affected by hypothyroidism due to Hashimoto’s thyroiditis, previously well compensated with a full replacement therapy (150 mcg/day of levothyroxine), presenting a clinical picture of myxedema, with a TSH=650 mU/L. Two years earlier she had started a dialysis treatment because of a chronic renal failure and had been under treatment for the last 18 months with sevelamer carbonate, a phosphate binder. No improvement of clinical conditions nor reduction in TSH serum levels was observed even on increasing the dose of levothyroxine up to 300 mcg/day, whereas euthyroidism finally restored by administering the first morning dose of sevelamer carbonate at least 4 hours after levothyroxine administration. This case shows that sevelamer carbonate, in analogy with what has been already reported for sevelamer hydrochloride, can interfere with levothyroxine absorption leading to a condition of hypothyroidism in patients previously well compensated with a given replacement dose.

In response to infection and trauma, exquisite control of the innate inflammatory response is necessary to promote an anti-microbial response and minimize tissue injury. Over the course of the host response, activated leukocytes are essential for the initial response and can later become unresponsive or undergo apoptosis. Leukocytes, along the continuum of activation to apoptosis, have been shown to generate microvesicles. These vesicles can range in size from 0.1 to 1.0 μm and can retain proteins, RNA and DNA of their parent cells. Importantly, neutrophil-derived microvesicles (NDMV) are robustly increased under inflammatory conditions. The aim of this review is to summarize the research to date upon NDMVs. This will include describing under which disease states NDMVs are increased, mechanisms underlying formation, and the impact of these vesicles upon cellular targets. Altogether, increased awareness of NDMVs during the host innate response may allow for diagnostic tools as well as potential novel therapies during infection and trauma.

This study documents that mumps virus shares several peptide sequences with human proteins that, when altered, may be involved in oligospermia/azoospermia, sterility and testicular atrophy. Examples are sperm flagellar protein 2 and spermatogenesis and centriole-associated protein 1. The data invite to further investigate crossreactivity as a potential mechanism linking anti-mumps immune responses, alterations of spermatogenesis–associated antigens and male fertility disorders.

Objective: To investigate the role of the Mediterranean diet and physical activity with relation to living environment and childhood asthma. Methods: 1125 children (529 boys), 10 to 12 years old were recruited either in an urban environment (Athens, n = 700) or rural environment (n = 425) in Greece. A path analytic model was developed to assess the causal relation between urban environment and asthma prevalence (standardized ISAAC questionnaire), through the mediation of the Mediterranean diet (evaluated by the KIDMED food frequency questionnaire) and physical activity (evaluated by the PALQ physical activity questionnaire). Results: The proposed model had a very good fit (χ2/df ratio =1.05, RMSEA=0.007, 90% confidence interval: 0.01 to 0.046, p=0.97, CFI = 0.98). A significant total positive effect was found between urban environment and asthma symptoms (standardized beta= 0.09, p<0.001). Adherence to the Mediterranean diet was related negatively with asthma symptoms (standardized beta = -0.224, p<0.001). An inverse mediating effect of the Mediterranean diet was observed for the urban environment – asthma relation (standardized beta=-0.029, p<0.001) while physical activity had no significant contribution (p=0.62), adjusted for several confounders. Conclusions: The Mediterranean diet may protect against the harmful effect of urban environment on childhood asthma.