Clinical Immunology, Endocrine & Metabolic Drugs (Discontinued) - Current Issue

Background: Interferons (IFNs) are functional proteins of vertebrate cells that have been conserved throughout evolution. Antiviral response in cells and uncontrolled cell proliferation of lymphocytes and macrophages are influenced by IFNs. B and T cell functions are influenced by these molecules in vitro and in vivo. These facts are confirmed by the effects on different conditions: antibodies production, T cells' cytotoxicity, allograft survival, delayed-type hypersensitivity reactions. Some IFNs are produced as a result of antigen recognition by T cells, and in turn, they modulate Natural Killer (NK) cell and phagocyte activities and functions. On the other hand, there are viral infections without immunological specificity, which involve IFNs and interfere in immune reactions. Some clinical applications of IFNs have been implemented in the recent years, for example for hepatitis B and C treatment. Conclusion: However, in this review, emphasis will be placed on the use of IFNs for the possible treatment of seasonal influenza viruses that have specificity with the upper respiratory tract. IFNs prevent highly pathogenic influenza viruses to disseminate to the lung, assuming their use as an emergency drug against pandemic forms of influenza.

Background: Polyethylene Glycols (PEGs) or macrogols are reputed to be inert and nonimmunogenic substances, however they are reported to induce immediate type hypersensitivity reactions. Due to their widespread use in extensively consumed products as cosmetics and drugs, the attention towards these substances is still low. Conclusion: Therefore, it may be useful to focus clinician's attention on possible adverse reactions caused by these polymers.

Background: Green tea has been consumed for thousands of years, and has been known to have many medicinal properties such as, anti-cancerous, anti-atherogenic, anti-oxidative, antiinflammatory and anti-bacterial. With the increasing prevalence of Cardiovascular Disease (CVD), and its major risk factor, obesity, there has been increasing interest in green tea as a potential antiobesity therapy. Evidence has demonstrated that green tea decreases body weight. However, it remains unclear through which pathway and mechanism green tea exerts its anti-obesity properties. The metabolic adipose tissue hormones, adipocytokines, leptin and adiponectin have been studied extensively as a potential target for green tea and its main catechin, Epigallacatechin Gallate (EGCG). Conclusion: It has been demonstrated that green tea consumption decreases leptin levels which may directly decrease body weight through increasing energy expenditure and fat oxidation. Furthermore, ingestion of green tea or its catechins has been associated with increased adiponectin levels which may indirectly reduce body weight through insulin sensitivity.

Background: Coffee intake represents an essential tradition in many people's lives all around the world: the success of this beverage is mainly due to its unique flavour and its well-known characteristic of reducing sleep. Coffee is usually associated with caffeine, nevertheless, hundreds of other molecules are involved in the very heterogeneous composition of the beans. Many studies revealed that several of these compounds can influence our health, because of their bioactive activities. Coffee appears as an antioxidant, antidiabetic, anticancer, and antidepressant agent and the data about these properties have been already reviewed. Conclusion: In the present work, the antimicrobial and the antiviral activities will be discussed. Attention will also be focused on single compounds present in beans: some coffee constituents appear as valid candidates to develop new efficient drugs and the available data show that more efforts are needed to fully investigate the potential of coffee against pathogens.

Background: In the 20th century, cancer metabolism has been studied from different aspects. In the last decade, the interest in this issue has been renewed and many studies have been carried out on tumor and endothelial metabolism. Although tumor metabolism is well recognized, there are some discrepancies between what we knew and what has been studied lately about the metabolism of endothelial cells. Moreover, cancer and endothelial cells are not alone in their microenvironment. Immune cells and fibroblasts are also present and have a crucial role in tumor-associated inflammation, as well as in tumor progression, metastasis and angiogenesis. Nevertheless, metabolism of these cells is poorly understood. Conclusion: In the present mini-review, information about metabolic characteristics of these cells is summarized and compared with our knowledge about cancer and endothelial cell metabolism. This knowledge could contribute to open up innovative approaches to the treatment of cancer.

Background: Previous experimental and clinical studies have shown that lactate concentrations of 10 mM and more in solid malignant tumors may inactivate cytotoxic T cells as a major component of the immune defense of the tumor host. Additionally, it has been demonstrated recently that glucose depletion within cancerous tissue to concentrations of 1 mM and less may inhibit the T cellmediated immune response, as well. To evaluate the significance of lactate accumulation compared to glucose depletion in cancers, we have revisited previous data using the technique of induced metabolic Bioluminescence Imaging (imBI) in various entities of human tumor xenografts and tumors in the clinic. These tumor entities comprise squamous cell carcinomas of the cervix and of the head and neck, ovarian cancer metastases, rectal adenocarcinomas, glioblastomas, and melanomas. Tissue lactate levels in metastatic primary tumors were 1.5- to 2-times higher than those in non-metastatic primaries, and this was true for both patient cancers and corresponding tumor xenografts. Immunologically relevant lactate accumulation (≥ 10 mM) occurred in a large majority of all tumors investigated. In contrast, tumors with average glucose concentrations of 1 mM and less were rarely found in general with the striking exception of rectal adenocarcinomas, where 67 % of all tumors were low glucose malignancies. Conclusion: lactate accumulation in malignant tissue may be quantitatively more relevant for the immune escape compared to glucose depletion. However, in rectal adenocarcinomas both high lactate and low glucose concentrations may substantially contribute to the inhibition of the immune defense.

Background: The discovery of fullerene by the end of 20th century has revolutionized nanoscience and nanotechnology. Since the inception of fullerene it has been one of the most attractive natural carbon molecules for the researchers from biological, biomedical fields and other varied industries. Fullerene is one of the allotropic forms of carbon. The physical and photo-electro-chemical properties of fullerene make nanomaterials suitable for biological and biomedical applications. Observations: Fullerene and its related compounds exhibit quite intense interaction with free radicals and it is considered as “radical sponge”. Fullerene molecules have the capacity to undergo chemical reactions and most of the interactions are related to either donate and/or accept the electron. Pristine fullerene is hydrophobic in nature and it gets agglomerated in aqueous medium resulting in the formation of its suspension. The interaction between fullerene and water is basically related to their specific properties like spatial, orientational dynamics, surface properties etc. Its utility is enhanced by its ability of forming water soluble derivatives. The existing derivatives of fullerene have become a significant research tool in the current scenario due to the enhanced multifaceted properties. Result: In almost all cases there exists correlation between the physicochemical properties of the product and the interacting biosystem. The impact or effect of the product may be toxic, neutral or good in nature to the organism. Fullerene and its derivatives exhibit various efficacies as generator and scavenger of ROS, RNS, antimicrobial, imaging agent, antiviral, toxic, drug delivery agents, etc. Fullerene and its derivatives interact with various biomolecules. These interactions may interfere with cell signaling process and cell functioning. This natural carbon allotropic form exhibits dual behavior that is related to the degree of efficacy of ‘covalently functionalized’ water soluble form of fullerene. Conclusion: In this article, an effort is made to survey the impact of this multifaceted allotropic form of carbon with reference to biosystem.

Background and Objective: Thalassemia is one of the most common hereditary disorders in the world, Beta thalassemia is much more diverse than the alpha type; it was estimated that about 4% to 7% of the world's population are carriers of beta thalassemia. In thalassemia, oxidative damage is increased, which causes damage to cellular components and functional disorders in the body. Oxidative injuries and stress are important factors for accelerating the aging process and the immune system response. Such frequent problems may cause local and systemic infections in the patients and financial damages to the society. Therefore, this study was performed to evaluate the strength of the immune response in patients diagnosed with thalassemia. Materials and Methods: This descriptive cross-sectional study was conducted in the Shafa Hospital Ahvaz. Peripheral blood samples were collected from patients with the beta-thalassemia minor (test group) and healthy individuals (control group) have been investigated. Results: Overall, 100 patients (48% female and 52% male) were enrolled and compared with the 100 healthy volunteers (56% femal and 44% male). There was no significant differences in the number of WBC between the case and control groups (P>0.05). In the case group, 94% and 6% of the patients had normal and high WBC, respectively. Conclusion: It can be concluded that patients with thalassemia may be at risk for local and systemic infections due to many resaons, which include increased oxidative stress and decreased antigen presentation by dendritic cells, defects in chemotaxis or phagocytosis, neutrophil and monocytes, impaired natural killer cells activity and the immune response, increasing the dose of iron, lymphocytes, and other immune cells functions.

Background: Abdominal obesity in adolescents has been identified as a risk factor for occurrence of cardiovascular and metabolic diseases. Objective: To monitor abdominal obesity in Roman adolescents through a five years-period. Method: A total of 410 adolescents aged 14.5-17.9 years, living in the city of Rome, were selected from two cross-sectional studies conducted during 2006-2007 (HELENA Study) (n=198) and 2011-2012 (ALIADO Study) (n=212). Anthropometric measurements such as weight, height and Waist Circumference (WC) were taken in both surveys using the same methodology and trained staff. Overweight and obesity were defined by both the latest IOTF (International Obesity Task Force) and WHO (World Health Organization) references, abdominal obesity as a Waist-to-Height Ratio (WtHR) ≥0.5. Smoking data were collected by questionnaire and socio-economic status was assessed using the education level of both parents. Results: A significant decrease in the mean value of WC in males (p=0.001) and of WtHR in females (p=0.002) was observed from 2006-2007 to 2011-2012. A decrease of abdominal obesity proportion was observed in female. Lower proportions of overweight and obese females were observed in 2011-12 than in 2006-07 using both criteria, IOTF and WHO. It was not found that smokers were more likely to have abdominal obesity. Conclusion: There is a decrease of abdominal obesity and a significant trend towards lower WtHR values in female adolescents from Rome (Italy). In males, despite a trend towards lower waist circumference values, the prevalence of abdominal obesity leveled- off.

Objective: Recent studies have demonstrated the importance of Endoplasmic Reticulum Aminopeptidase 1 (ERAP1) gene variants in inflammatory conditions, including Type 1 diabetes mellitus. However, to date, no large prospective, genetic-epidemiological data are available on the relevance of ERAP1 genetic variation in the risk of non-insulin dependent diabetes. Methods: The association between 33 tag-SNPs (tSNPs) of ERAP1 and incident Type 2 Diabetes mellitus (T2D) was investigated in 22,718 Caucasian female participants of the prospective Women's Genome Health Study. All were free of known cancer, cardiovascular disease, and diabetes mellitus at baseline. During an 18-year follow-up period, 1,927 newly diagnosed first ever T2D were identified. Multivariable Cox regression analysis was performed to investigate the relationship between genotypes and T2D risk assuming an additive genetic model. Results: None of the gene variants evaluated were associated with T2D risk. Conclusions: If corroborated in other large prospective studies, the present findings suggest that genetic variation within the ERAP1 gene locus may not be useful prognostic indicators for risk assessment of type 2 diabetes mellitus.