[Correlation among measures of stress, indicators of biohumoral nature and medico-legal considerations]. / Correlazione fra misure di stress, indicatori di natura bioumorale e considerazioni medico-legali.

INTRODUCTION: Man devotes most of the daily time to work, and also a large part of physical and mental resources. Depression and many other morbid conditions can be related etiopathologically to the performance of a dangerous occupation in terms of quality (hazardous work activities, lack of motivation for deficient career opportunities) or merely quantitative (duration of work shifts, frequency shifts work). The medical legal ascertainment is limited because stress cannot be valued by objective nature, but only through precious elements collected directly by workers by questionnaires. This is in response to legal requirements in terms of civil liability, occupational disease and disability. AIM AND METHODS: The objective of this study is to analyze the change of cytokines (IL-6, IL-12, TNF-α) and stress-related hormones (prolactin and cortisol) in a sample of 314 individuals working at the University Hospital Umberto I in Rome without acute diseases but only with the "feeling stressed" for at least a month and to analyze if there is a correlation between some of these biochemical variables and stress values measured by questionnaire. RESULTS: The results of this study confirm the usefulness to associate laboratory analysis, such as the study of inflammatory cytokines and the hormonal profile, to psychometric tests, precious for the lower cost and in some cases also for the high diagnostic sensitivity, to reach a probative value which satisfies even the most demanding application of accuracy.

Stress and obesity as risk factors in cardiovascular diseases: a neuroimmune perspective.

Obesity is now growing at an alarming rate reaching epidemic proportions worldwide thus increasing morbidity and mortality rates for chronic disease. But although we have ample information on the complications associated with obesity, precisely what causes obesity remains poorly understood. Some evidence attributes a major role to a low-grade chronic inflammatory state (neurogenic inflammation) induced in obesity by inflammatory mediators produced and secreted within the expanded activated adipocyte pool. Adipose tissue is an endocrine organ that secretes numerous adipose tissue-specific or enriched hormones, known as adipokines, cytokine-like molecules thought to play a pathogenic role in cardiovascular diseases. The imbalance between increased inflammatory stimuli and decreased anti-inflammatory mechanisms may depend on chronic stress. Hence the positive correlation found between stress, obesity and cardiovascular diseases. The chronic inflammatory state associated with insulin resistance and endothelial dysfunction is highly deleterious for vascular function. This review focuses on the proposed neuroimmunodulatory mechanisms linking chronic (psychological) stress, obesity and cardiovascular diseases.

Alzheimer's disease promotion by obesity: induced mechanisms-molecular links and perspectives.

The incidence of AD is increasing in parallel with the increase in life expectancy. At the same time the prevalence of metabolic syndrome and obesity is reaching epidemic proportions in western populations. Stress is one of the major inducers of visceral fat and obesity development, underlying accelerated aging processes. Adipose tissue is at present considered as an active endocrine organ, producing important mediators involved in metabolism regulation as well as in inflammatory mechanisms. Insulin and leptin resistance has been related to the dysregulation of energy balance and to the induction of a chronic inflammatory status which have been recognized as important cofactors in cognitive impairment and AD initiation and progression. The aim of this paper is to disclose the correlation between the onset and progression of AD and the stress-induced changes in lifestyle, leading to overnutrition and reduced physical activity, ending with metabolic syndrome and obesity. The involved molecular mechanisms will be briefly discussed, and advisable guide lines for the prevention of AD through lifestyle modifications will be proposed.

Montelukast therapy and psychological distress in chronic obstructive pulmonary disease (COPD): a preliminary report.

Chronic obstructive pulmonary disease (COPD) is an alteration in which ventilatory function, exercise capacity and health status of patients progressively decline and it is characterized by an increase of inflammatory cytokines such as TNF-α, LTB4, IL-8, etc. In this study we considered twenty patients (15 males and 5 females; mean age: 72.8 ± 6.3) with stable COPD. All patients were performed evaluation of psychological stress at enrollment and were treated with leukotriene receptor antagonists (montelukast tablets) 10mg/day for 12 months. After 12 months we observed a significant decrease of serum levels of LTB4, IL-8 and also a decrease of the number of outpatient clinic visits, of the number of hospitalizations and of the duration of hospitalization.

Inflammation is the main determinant of low bone mineral density in pediatric inflammatory bowel disease.

AIMS: To assess bone mineral density (BMD) in children with Crohn's disease (CD) and ulcerative colitis (UC) and to investigate the role of inflammation and steroids on BMD. METHODS: Lumbar spine areal BMD was measured by DXA, and volumetric BMD was then estimated (BMAD); inflammatory cytokines (TNF-alpha, IL-6, IL-10, and IL-12) were dosed in peripheral blood; and cumulative and daily doses of steroids were calculated. Therapy with infliximab (IFX) was considered for CD patients. RESULTS: Fifty-six patients with IBD (35 CD, 21 UC) were studied. An inverse correlation was found between BMAD and IL-6 in patients with UC (r = -0.65); no correlation was found between BMAD and serum levels of TNF-alpha, IL-10, and IL-12 in all patients. Disease activity indexes use inversely correlated with BMAD (r = -0.62 in patients with CD and r = -0.64 in patients with UC). Cumulative dose of corticosteroids and duration of therapy did not correlate with BMAD. The 10 patients with CD who were treated with IFX had higher BMAD (-1 +/- 0.8) than those never treated with IFX (-1.8 +/- 0.8). Mean Pediatric Crohn's Disease Activity Index and body mass index in patients with CD (R(2) = 0.48) and IL-6 level in patients with UC (R(2) = 0.43) were found to be independent and significant predictors of BMAD. CONCLUSIONS: In children with IBD, inflammation is an important determinant of bone loss, as shown by the correlation of BMAD with serum IL-6 and with disease activity indexes as well as by the beneficial effect of IFX on bone density. Corticosteroids seem to be a less important variable in pediatric IBD-related BMD reduction than previously believed.

Psychological stress affects response to sublingual immunotherapy in asthmatic children allergic to house dust mite.

While the clinical and immunologic efficacy of sublingual immunotherapy (SLIT) in allergic diseases has been extensively demonstrated, some patients display a poor clinical response. Psychological stress has been shown to play a role in atopy and also to affect response to immunomodulating therapies such as vaccination with microbial antigens. This study addresses the possibility of response to SLIT being affected by psychological stress. Forty children with mild asthma caused by allergy to Dermatophagoides pteronyssinus and farinae were subjected to SLIT and then divided after 6 months into two groups based on the results of the stress integrated measure (SIM) test: group 1 (24 stressed patients, mean SIM value of 60.1) and group 2 (16 non-stressed patients, mean SIM value of 7.6). There was also a higher prevalence of psychosocial stressing factors (divorced/absent parents, low income households, non-working parents) among stressed patients. The symptom score, peak expiratory flow (PEF), forced expiratory volume in 1 s (FEV(1)) and serum eosinophie cationic protein (ECP) concentration were evaluated at both times. The serum concentration of neuroendocrine parameters [prolactin, cortisol, adrenocorticotropic hormone (ACTH)] was also measured after 6 months of therapy. While all the clinical parameters and ECP concentration improved after SLIT, symptom score, PEF and ECP showed a significantly greater improvement in non-stressed patients. The concentration of neuroendocrine parameters was significantly increased in stressed patients. Our findings show that psychological stress can affect response to SLIT also in allergic subjects and are consistent with data recently reported showing a correlation between stress and poor response to antimicrobial vaccines. Our data also suggest that stress evaluation may become a useful prognostic factor in immunotherapy.

[Biomonitoring of nurses occupationally exposed to antineoplastic drugs: the IMEPA Project]. / Identificazione di marcatori specifici di esposizione professionale a farmaci antiblastici usati in polichemioterapia: Progetto IMEPA.

OBJECTIVE: To develop a multiple-endpoint monitoring system in order to assess and minimize long term risks in hospital nurses exposed to antiblastic drugs. DESIGN: Molecular epidemiology study. SETTING: S. Orsola-Malpighi Hospital in Bologna, Italy: nurses exposed to antiblastic drugs. PARTICIPANTS: 50 exposed subjects (8 males and 42 females) and 50 unexposed individuals (8 males and 42 females) matched for age and smoking habits. MAIN OUTCOME MEASURES: Urinary markers of exposure, Heat Shock Proteins (HSPs) 27, 70, 90, 110, immunologic biomarkers in peripheral blood lymphocytes: apoptosis, cell-cycle analysis G1-S-G, typization of Natural Killer cells (NK) and receptors micronuclei; frequency in peripheral blood lymphocytes and in exfoliated buccal mucosa cells; activation ofspecific oncogenes (bax, bcl2). RESULTS: 19/50 subjects showed urinary antiblastic drug levels (3 subjects MTX, 11 subjects CP, 5 subjects MTX and CP). No statistically significant differences were observed in all the considered biomarkers between the exposed and control groups. CONCLUSION: This biomonitoring study doesn't evidence any early significant effect associated to the exposure to antiblastic drugs.

Immunomodulation during sublingual therapy in allergic children.

The clinical efficacy of sublingual immunotherapy (SLIT) has been demonstrated, but its mechanism of action is still controversial. The most recent experimental observations suggest that a critical role in the modulation of immune response is sustained by Th2 cytokines, such as interleukin-4 (IL-4), IL-5 and IL-13, by co-stimulatory molecules, such as CD40 on B cells, and by hormones and neuropeptides. To better understand whether SLIT affects immune responses we used a double-blind placebo-controlled design. Eighty-six children with mild asthma due to allergy to Dermatophagoides pteronyssinus (33 of whom also had rhinoconjunctivitis) were randomly assigned SLIT (n = 47) or placebo (n = 39). We assessed symptom scores using diary cards of each patient and determined the expression of CD40 on B cells and the serum concentration of ECP, IL-13, prolactin (PRL) and ACTH at enrolment and after 6 months of therapy. We observed a significant reduction in asthma and rhinitis scores in the immunotherapy group compared with the placebo group, no variation in CD40 and ACTH, but a significant decrease in ECP, IL-13 and PRL after 6 months of therapy (p <0.01). Our results confirm the efficacy and safety of SLIT, and lead us to believe that it could modulate the synthesis of Th2 cytokines, as revealed from the decrease of IL-13. In addition, the reduction of PRL might be a signal of reduced activation of T lymphocytes.