Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders) - Volume 16, Issue 3, 2016

Cigarette smoke (CS) accounts for the outcome of several pathologies, even including lung cancer, cardiovascular disease and chronic obstructive pulmonary disease (COPD). Under healthy conditions, lung immune system becomes tolerant in response to various external stimuli. CS exposure alters the pulmonary immune equilibrium, thus leading to a condition of hyper activation of the local innate and adaptive immunity. COPD is one of the major complications of chronic CS exposure where a pro-inflammatory profile of the pulmonary and systemic immunity is predominant. In this review, alternative treatments with natural products to mitigate CS-mediated pulmonary inflammation are proposed. In particular, polyphenols, a class of natural compounds largely present in fruits and vegetables, have been shown to act as anti-inflammatory agents. Accordingly, recent experimental and clinical evidences support polyphenol-mediated potential health benefits in smokers. For instance, pomegranate juice is able to attenuate the damage provoked by CS on cultured human alveolar macrophages. In addition, maqui beery extract has been proven to normalize H2O2 and interleukin-6 levels in exhaled breath condensate in healthy smokers. However, some limitations of alternative treatments are represented by a better knowledge of the mechanism(s) of action exerted by polyphenols and by the lack of animal models of COPD. In any case, the potential targets of polyphenols in the course of COPD will be outlined with special reference to the activation of T regulatory cells as well as to the inhibition of the polymorphonuclear cell and monocyte respiratory burst and of the NF-ΚB pathway, respectively.

Introduction: Methadone is the most common opioid in use for opioid substitution therapy. The relation of methadone and electrocardiographic findings is nearly well known while the relationship between its electrocardiographic indexes and hormonal changes is not well recognized. Objective: To evaluate the hormonal changes in patients who are taking methadone maintenance treatment (MMT) and its effects on electrocardiographic indexes, in comparison with healthy control groups. Patients and Methods: 40 patients receiving MMT therapy for at least last six months and 40 healthy subjects were enrolled in the study. Serum estradiol, testosterone, luteinizing hormone, follicle stimulating hormone and thyroid function tests were measured. Mean QT Interval, P-R Interval (PRi) and QRS duration were also documented in maximum. Results: There were no significant differences in hormonal parameters between MMT and control groups. No significant relation was found between hormonal parameters, dose and duration of methadone usage in patients group. QTc was significantly higher in methadone users than control groups. QTc had a significant negative correlation with Testosterone level (r=-0.581, P=0.007) in males. Significant difference was found between PRi in patients and control groups (P=0.007). Conclusion: Electrocardiographic changes are an important complication of methadone that seems to be related to low testosterone level in men.

Background: Sleep alterations can impair quality of life and contribute to disease progression but they, and their features and contributing factors, are rarely analysed in institutionalised older individuals. In this study, we investigated sleep alterations, the factors involved, and the role of cortisol in sleep-related problems in institutionalised individuals. Methods: We conducted a descriptive cross-sectional study in participants living in nursing homes in Valencia (Spain); sleep alterations were determined based on two validated tools: the Athens insomnia scale and Oviedo sleep questionnaire. Plasma cortisol was measured in the morning and determined by high performance liquid chromatography-mass spectroscopy, along with other blood analytical parameters. We also analysed any confounding factors (sleep duration, morning awakening time, intake of hypnotic and psychotropic medication, and cognitive function). Results: The mean age was 82.5 years (range: 65-99); approximately 80% were women and sleep alterations were present in 25-60% of the population, depending on the scale used or type of sleep disorder considered. There was no significant correlation between morning cortisol concentrations and sleep disorders, sex, age, or psychotropic drug ingestion (including hypnotic drugs). However, there was a significant correlation between cortisol and an Oviedo questionnaire subscale for evaluating insomniarelated adverse events, which remained significant after adjusting for multiple potentially confounding factors. Conclusion: Sleep disorders are common in institutionalised older individuals and are not related to sleep duration or decreased by ingestion of hypnotic medications. There is a significant relationship between morning cortisol levels in blood and insomnia-related sleep disorders (e.g. snoring with awakenings, nightmares, restless legs syndrome, etc.) but not directly with insomnia or hypersomnia.

Background: ‘Beta thalassemia is inherited hemoglobin disorder resulting in chronic hemolytic anemia that requires lifelong transfusion therapy’. ‘Repeated blood transfusions and RBCs hemolysis are the main causes of iron overload’, which in addition to immune abnormalities, are common predisposing factors to infections in patients with thalassemia. The Aim of this Work: The aim of this work was to study immune status including T lymphocyte subsets and serum immunoglobulin levels ‘in children with beta- thalassemia in correlation with iron overload’. Patients and Methods: The present ‘study was conducted on 40 children with beta thalassemia major under follow up at Hematology Unit, Pediatric Department, Tanta University’ ‘including 24 males and 16 females with mean’ age value of 9. 22 ± 3.9 years and 20 ‘healthy children of matched age and sex as a control group’. All children included in the study were subjected to; ‘complete blood count, Hb electrophoresis, serum iron status’, T cell subsets including CD3, CD4 and CD8 and serum immunoglobulin levels including IgM, IgA and IgG. Results: ‘Pallor and jaundice were the most common presenting’ clinical manifestations. Infective episodes ‘were significantly higher in patients’ compared with controls. There were significantly lower Hb, MCV and MCH levels and significantly higher WBCs and platelets counts, reticulocytes and lymphocytes percentage in patients than controls and no significant differences in MCHC between patients and controls. Serum ferritin and iron were ‘significantly higher but TIBC was significantly lower in’ patients than controls. CD3, CD4 and IgM were significantly lower but CD8, IgG, and IgA ‘were significantly higher in patients than controls’ with negative correlation between CD3, CD4, IgM and ferritin and positive correlation between CD8, IgG, IgA and ferritin. Conclusion: Iron overload can affect humeral and cell mediated immunity in patients with beta thalassemia with reduction of IgM, CD3 and CD4 and elevation of CD8, IgG, and IgA. Recommendations: Regular follow up of patients with beta thalassemia for detection of iron overload as it affects humeral and cell mediated immunity.

Background: Our recent findings have demonstrated that electromagnetic radiations (EMR) (1.8 GHz radiofrequency) are able to in vitro induce morphometrical and morphological modifications of human leukocytes from normal donors. Methods: In view of the evidence that polyphenols exert many beneficial effects on plants, animals and humans, leukocytes from human peripheral blood were pre-treated for 1 h with two polyphenol preparations from red grape before EMR exposure (1.8 GHz). Results: Our data will show that polyphenol pre-treatment reverts to normality the morphology of irradiated leukocytes in comparison to irradiated cells only. Conversely, leukocyte morphometry seems to be not affected by this treatment. Conclusion: Here, we demonstrate that polyphenols are also able to normalize leukocyte morphology per se altered before as well as after irradiation. Finally, a working hypothesis aimed at clarifying the protective mechanisms exerted by polyphenols on irradiated leukocytes will be illustrated.

Background: The study of fungal contamination in food and mycotoxicoses is a priority today, both internationally and nationally. The purpose of this study is to have a general view over the quality of the most common spices that are sold in Romanian markets, by assessing the degree of fungal, bacterial and mycotoxin contamination in pepper and chili powders. Methods: We tested four types of spices: white pepper, black pepper, sweet and hot chili powders from 12 different distributing companies, summing a total of 35 sample types. The fungal and bacterial load was assessed by Standard Plate Count, while the mycotoxin content by High-performance liquid chromatography. Environmental conditions (humidity, pH) and the selling price for each product were also followed. Results: Fungi were observed in 72.7% of black pepper samples, 33.3% in white pepper, 30% in sweet chili and 25% in hot chili products. The most common isolated fungus was Aspergillus spp., while Rhizopus, Mucor, Fusarium, Penicillium, Absidia species were found, in smaller percentage. Four producers (44.4%) presented fungal contamination of over 10^3 CFU/g and two producers (22.2%) presented no fungal contamination in their products. Bacterial contamination was found in 85.7% of the tested products, consisting mostly in Bacillus spp. Aflatoxin B1 was present in all the tested products, mostly in black pepper (mean value 126.3 ng/g); Ochratoxin A was present in sweet chili (mean value 328 ng/g) and Zearalenone in hot chili (mean value 604 ng/g) and sweet chili (mean value 382 ng/g). Conclusion: All spices presented either fungal contamination, mycotoxin contamination, or both. The high humidity and the high pH of spices represent favorable conditions for fungal growth. The selling price was partly related to the physic-chemical conditions and microbiological quality of the spices.

Background: Preventing liver damage that might lead to cirrhosis is very important in the early stages of injury to that organ. The role of mast cells (MCs) in liver injuries has been long debated, and vitamin E is a well-known antioxidant used to treat those injuries. This study aimed to determine the protective role of vitamin E on MCs in injury to the liver that is triggered by carbon tetrachloride (CCl4). There is a correlation between MC deposits and improvement in fibrosis tissues. Methods: To further examine this, 68 male Albino Wistar rats were divided randomly into five groups: the control group, the vitamin E group, the CCl4 group, the CCl4 + vitamin E group, and the vitamin E + CCl4 group. Malondialdehyde (MDA) analysis, MC counts, histopathological investigation, and statistical analyses were used to evaluate the findings. Results: The administration of CCl4 resulted in an increase in the accumulation of MCs, degenerative parenchyma cells, MDA level, steatosis and inflammation. Additionally, proliferation of the bile ducts in the portal area and porto-portal and porto-central fibrosis were observed in the CCl4 group. In contrast, in the vitamin E group and in the groups administered a combination of vitamin E and CCl4, vitamin E prevented these increases. Conclusion: It was concluded that the significant decrease in the MC counts, in the level of MDA and the number of degenerative cells, as well as a decrease in the steatosis and inflammation scores showed that vitamin E could prevent liver injuries by protecting the organ’s histological architecture. Finally, the results indicate that vitamin E has positive effects on liver injuries.

Background: Human autoimmune diseases are caused by a variety of factors, such as environmental chemicals, including para-nonylphenol. Macrophages play many critical roles in the regulation of immunity and the progression of autoimmune diseases. However, little information is available regarding the effects of para-nonylphenol on cellular signaling pathways and the death of these cells in vitro. Here, we show that very high concentrations of para-nonylphenol (50-100 μM) induce apoptosis in U937 human monocyte leukemia cells in a dose-dependent manner. Methods: Cell viability was judged using the trypan blue exclusion method. FACS analysis for DNA fragmentation was conducted, cellular signaling pathways were evaluated using western blot analysis, and caspase activity was measured by using substrates. U937 cells were differentiated by PMA. Results: Treatment with > 50 μM para-nonylphenol induced apoptosis in U937 monocyte cells and MCF- 7 and MDA-MB231 human breast cancer cells. We found cytochrome c release from the mitochondria to the cytoplasm, DNA fragmentation, and decreased expression of anti-apoptotic protein Bcl-XL. Caspase 3 and 9 were induced, but caspase 1 and 3-inhibitor treatment suppressed apoptosis. Para-nonylphenol decreased the levels of activated AKT and increased the levels of activated JNK/SAPK at 15 min after treatment. Furthermore, with PMA treatment, U937 cells were differentiated into a macrophage-like phenotype and showed attenuated cell death against para-nonylphenol. Conclusion: As this assay system is simple and rapid, it may represent a useful artificial tool to clarify the signaling pathways of apoptotic cell death in human monocytes in vitro.

Background: Studies have already shown that hyperglycemia and insulin resistance are significantly associated with the impairment of cerebral glucose metabolism that may secondary lead to cognitive disturbances. In this study, we aimed to evaluate the neurometabolic correlates of diabetes in a patient with Intermittent explosive disorder (IED). Methods: We have investigated the cerebral glucose metabolism via 2-[18F]-fluoro-2- deoxy-D-glucose positron emission tomography (FDG-PET) in a diabetic patient with aggressive outbursts. Results: We have found significantly reduced glucose uptake in left temporoparietal region, pontin area, and left nucleus lentiformis. Discussion: Our present results indicate decreased cerebral glucose metabolism in specific cerebral cortical and subcortical areas. The main limitation of this report is that, this is a single case study and that these findings need to be replicated in well- conducted randomized controlled studies by using additional neuroquantitative methods.