Clinical Immunology, Endocrine & Metabolic Drugs (Discontinued) - Volume 1, Issue 2, 2014

An analytical review of the articles published in the two issues of Clinical Immunology Endocrine Metabolic Drugs (volume 1, 2014) is reported. Various topics are covered in volume 1 of the journal. Clinical Immunology is represented in six articles related to nickel hypersensitivity (2 articles), therapeutic approaches in human tuberculosis, immune biomarkers in trauma patients, salivary cytokines in normal weight children and oral sensitization in rats. Endocrinology is the main topic of the two articles dealing with polycystic ovary syndrome and androgen receptor antagonists in prostate cancer. The vascular pathophysiology is the major theme of two papers dealing with the role of angiotensin II and post-prandial oxidative burst. Finally, a paper is devoted to antibiotics resistance of four probiotics.

Nickel is a chemical element found ubiquitously in the environment and is used with a high frequency worldwide. Nickel hypersensitivity could give rise both to contact dermatitis and to systemic contact dermatitis, the latter, as expression of ingestion or other systemic exposure to a contact allergen. The common clinical presentation of nickel allergic contact dermatitis (ACD) is more often a vesicular pruritic dermatitis in sites of prolonged skin contact with nickel-containing items. Patients can develop acute (bright red rash, edema and vesicle), subacute (less erythematous and edematous lesions, minimal vesiculation, and excoriation) and chronic manifestations (fissuring, scaling, excoriation and mild form of erythema). Systemic contact dermatitis is induced in sensitized individuals when they are exposed to a hapten systemically. In the detection of contact allergy, and in the diagnosis of ACD, patch test is the generally accepted method of choice and the “gold standard”. Their execution increases the probability of correct diagnosis, shortens the time lapse between first visit and final diagnosis, increases the chance for full remission, and reduces therapy costs. Management of nickel allergy is still complex for dermatologists. Between 1994 and 2009, nickel allergy showed a decreased in morbidity; however, after 2000, there was no significant decrease. Exposure to nickelcontaining products exceeding the permitted limit may explain the high persistence of nickel contact allergy in population. In 2001 the European Union, to reduce the exposure to nickel, introduced standards for the productions of tools intended for prolonged skin contact.

Nickel is the major cause of allergic contact dermatitis. It is a widely spread metal, being therefore very difficult to avoid. Nickel cutaneous allergy can occur in occupational and non-occupational contexts and can result from direct cutaneous contact, systemic as well as airborne exposure. Such allergy can manifest with typical lesions of allergic contact dermatitis or with peculiar features such as follicular erythemato-micropapularvescicular lesions. Diagnosis of allergic contact dermatitis to nickel is based on patch testing, employing nickel sulfate 5% in petroleum jelly. Reactions to patch test have to be assessed at 48-72 hours, and up to 6 days. Nickel contact dermatitis can be managed with the traditional therapeutic approach used in allergic contact dermatitis. As of today, hyposensitization therapy with oral nickel represents to be the only treatment acting on the pathogenetic mechanisms of nickel allergy.

In western societies, dietary habits are often characterized by hypercaloric food ingestion, and this seems to account for the outcome of chronic pathologies, even including obesity and diabetes. On these grounds, we enrolled 20 normal weight schoolchildren who received healthy eating recommendations. Then, over a period of one year body mass index (BMI), physical activity (PA), and salivary levels of interleukin (IL)-10 and IL-17 were measured at time 0 (baseline), at time 1 (after six months) and at time 2 (after one year, even including the summer pause). At T1, in children who followed dietary eating recommendations (group “a”) BMI decreased, while in children who did not follow dietary recommendations (group “b”), BMI significantly increased. Decrease in PA was associated to an increased BMI and viceversa. In terms of salivary cytokine levels, in group “b” children values of IL-17 augmented at T1 and at T2. On the other hand, in group “a” children values of IL-17 diminished both at T1 and at T2. Moreover, in group “b” children, IL-10 salivary levels decreased at T1 and at T2. Viceversa, in group “a” children IL-10 significantly increased at T2. Of note, BMI variations, even if statistically significant, fluctuated within normal ranges and no change of BMI cutoff points seems to be applicable. In conclusion, according to the present results, no adherence to healthy dietary recommendations with increase in BMI and reduction in PA seems to correspond to a more inflammatory profile (increase in IL-17). Conversely, adherence to healthy eating recommendations with higher PA and lower BMI seems to be associated to an anti-inflammatory profile (increase in IL-10).

Animal models of food allergy can provide advances in the aetiology, pathogenesis and therapeutic treatment of this disease. The aim of the present study was to set up a model of oral sensitization in rats by testing seven different procedures and using ovalbumin (OVA) as the antigen. Brown Norway and Lewis rats aged between three and eight weeks old received, orally, different doses of the OVA together with or without cholera toxin (CT) under several dosages. Isotypes of anti-OVA antibodies were determined weekly in serum and also in intestinal samples (faecal or gut lavage). In the most successful procedure, mesenteric lymph nodes (MLN) and intestine samples were excised to determine cytokines and gene expression related to allergic response, respectively. In both Brown Norway and Lewis rats, the quantification of specific antibodies revealed that CT was required to increase oral sensitization. In addition, OVA dosage, age and sex of animals are important in the oral sensitization of Lewis rats. Serum anti-OVA antibodies mainly belonged to IgG1 and IgG2a isotypes, and intestinal anti-OVA immune response was almost undetectable. Specific IgE was not found in the serum of any of the studied procedures, and cytokines from MLN did not clearly demonstrate a Th2 immune response. The gene expression study in small intestine samples of sensitized rats suggested changes in IL-10 and TLR-5 mRNA expression. In summary, oral sensitization in rat could be achieved in both young Brown Norway and young female Lewis rats.

Recently has been acknowledged the healthy use of Bacillus and related bacteria as probiotics. A mixture reported to contain four probiotic strains of Bacillus clausii is marketed as an OTC (Over The Counter) medicinal supplement for human use. Their poliantibiotic resistant property, useful for restoring the gut microbiota during antibiotic treatment, raises the question about the risk of resistance transfer. In order to better assess the risk-benefit ratio it is important to always monitoring the pattern and stability of resistance spectra in these bacteria. In this work, we have extensively redefined the antibiotic susceptibility profile of these four probiotic strains. Resistance phenotype has been determined by screening a large number of antibiotics, including natural products (such as penicillin, vancomycin and erythromycin), and completely synthetic molecules (such as fluoroquinolones). Extensive comparison with a wild type strain belonging to the normal intestinal microbiome was carried out. The molecular basis of some resistances was determined. Observed antibiotic resistances were correlated with previous and new data in safety evaluations of these strains for human use.

This study was performed to investigate the relationship between markers of inflammation in serum, severity of injury and clinical outcome and also to evaluate the predictive value of these markers for major complications and mortality. We recruited patients of either sex aged ≥16 years and upto eight hours after trauma with severe condition and SBP ≤90 mmHg at the time of admission in Emergency Department of the Trauma Centre. Blood samples were collected at different time points on day 0, 3, 7 and 14 to measure the serum level of cytokines and compared with severity scores of the patients. Baseline serum levels of IL-10 and TNF-α, together with the IL-10: TNF- α ratio had a significant prognostic value as these values were significantly higher in patients who died within 72 hours of injury. We noticed that among patients, serum levels of TNF-α significantly discriminate the survivors from the non-survivors. Serum levels of IL-6 and IL-10 were significantly (p<0.005) elevated in patients who died early (<72 hrs) from those who survived and it showed positive correlation with SOFA score and also discriminated the survivors from non-survivors. Serum levels of TNF-α, IL-10 and IL-6 on day 0 showed good accuracy for predicting the occurrence of early mortality (<72 hours). The present prospective study is the first largest series from India and provides an evidence of correlation between serum levels of IL- 6, IL-10 and TNF-α with injury severity and the incidence of MODS in THS patients.