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OBJECTIVE: The nerve growth factor (NGF) is the main neurotrophin, which, besides being an important growth factor for nerves, plays an important role as a mediator of inflammation. Nerve growth factor has been shown to increase in relation to stress stimuli and in allergic diseases in humans as well as after physical exercise in animal models. This study aims at evaluating NGF serum levels in top athletes, a population sample in which allergic and neuro-immune diseases are reported with a significantly increased prevalence. DESIGN: Observational, cross-sectional, multicenter study. SETTING: Institutional, tertiary care. PARTICIPANTS: Ninety-six Italian pre-Olympic athletes (44 allergic and 52 nonallergic) and 49 matched controls selected within the Italian National Olympic delegation (n = 435). INDEPENDENT VARIABLES: Nerve growth factor serum levels determined through an enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: Parametric or nonparametric tests were used for comparing NGF serum levels among different study groups depending on value distributions. RESULTS: Nerve growth factor serum levels were significantly higher in athletes than in controls independently from the presence of allergy. Nerve growth factor mean values were 368.3 ± 776.3 pg/mL in the sample of athletes and 174.1 ± 483.7 pg/mL in the control group (P < 0.001). CONCLUSIONS: This is the first study showing that intense and prolonged physical exercise is associated with an increase of NGF serum levels in athletes. Whether the increased NGF production might be linked to the prevalent Th2 response observed in allergic diseases and after physical exercise and whether it might be related to the patophysiology of neuro-immune disorders as such amyotrophic lateral sclerosis, reported with a higher prevalence in athletes, should deserve further investigations.

Purpose: Salmeterol is a s2-adrenergic receptor agonist widely used for the treatment of asthma and chronic obstructive pulmonary disease. It has been shown that salmeterol is also used at supratherapeutic doses as performance-enhancing substance in sport practice. Although the abuse of s-agonists might determine some adverse effects, the molecular effects of salmeterol on skeletal muscle cells remain unclear. Methods: We evaluated the effects of salmeterol (0.1�10 µM) on both proliferative and differentiated rat L6C5 and mouse C2C12 skeletal muscle cell lines. The metabolic effects were evaluated by glyceraldehyde phosphate dehydrogenase, lactate dehydrogenase, citrate synthase, 3-OH acyl-CoA dehydrogenase, and alanine transglutaminase activities. Cytotoxic and apoptotic effects were analyzed by 3-(4,5-dimethylthiazol-1)-5-(3-carboxymeth-oxyphenyl)-2H-tetrazolium, trypan blue exclusion assay, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, Western blot analysis, and immunofluorescence staining. Results: We showed that salmeterol reduced the growth rate of proliferating cells in a dose- and time-dependent manner (6�48 h). An increase in oxidative metabolism was found after 6 h in C2C12 and L6C5 myoblasts and in C2C12 myotubes with respect to control cells, while in L6C5 myotubes, anaerobic metabolism prevailed. Exposure of myoblasts and myotubes for 48 and 72 h at high salmeterol concentrations induced apoptosis by the activation of the intrinsic apoptotic pathway, as confirmed by the modulation of the apoptotic proteins Bcl-xL, caspase-9, and poly (ADP-ribose) polymerase and by the cytoplasmic release of Smac/DIABLO. Conclusions: Altogether, our results demonstrate that short-term supratherapeutic salmeterol exposure increased oxidative metabolic pathways on skeletal muscle cells, whereas prolonged treatment inhibits cell growth and exerts either a cytostatic or a proapoptotic effect in a time- and dose-dependent way

Purpose of review Multiple action drugs, such as azelastine, epinastine, ketotifen and olopatadine, have recently been suggested to combine antihistaminic effect, mast cell stabilization and anti-inflammatory action. This pharmaceutical class is, therefore, rapidly becoming the first choice for prevention and treatment for allergic conjunctivitis. Recent findings Increasing in-vitro studies have been performed to investigate the mast-cell-stabilizing effect of multiple action drugs. Most of the study results agree that these drugs are able to inhibit histamine and several neoformed mediators, including cytokines and arachidonic acid-derived products, from mast cells. However, the mechanisms of action have not yet fully been elucidated. Most of the results from clinical trials as well as the in-vivo experimental studies, including the conjunctival provocation model, support the evidence of a stabilizing effect of these drugs. Summary Evidence of a different inhibitory effect of multiple action compounds on the pro-inflammatory mediators released from the mast cells suggests the possibility to target different phases of the allergic reaction, leading to a potential improvement in the management of allergic patients.

Purpose:Despite the high and increasing prevalence of allergic diseases in athletes, allergy diagnostics is not part of the routine medical examination in sports medicine. This study reports the development and validation of an easy and reliable questionnaire for screening allergy in athlete

Purpose of review This article intends to be a systematic review of papers published during 2003-2004 quoted in a Medline search for 'hygiene hypothesis'. The worldwide perspective of the article does not refer just to a geographical concept, but tries also to address the question of whether the consensus on the hypothesis is global or whether it applies to all types of allergic or immunologic disease, to any age sample or infectious agent. Furthermore, the article outlines those clinical and experimental studies which, in the authors' opinion, may represent significant contributions to a better understanding of the hygiene hypothesis and may guide further investigations on the subject. Recent findings The association between a reduced exposure to infectious agents (as a part of a changed lifestyle) and a higher prevalence of atopy seems now to be confirmed by consistent evidence. Mechanisms underlying this association, however, are not yet completely clear (immune deviation or immune regulation). Summary Further experimental and clinical studies are needed, with special reference to the time, duration and intensity of exposure to any specific infectious agent which is related to well-defined allergy outcomes. The background information for using microbial products in allergy prevention and treatment is still limited.

This editorial comments on the paper of Pedersen et al. focusing, in particular, on the criteria set by the IOC-MC for documenting exercise-induced asthma and exercise-induced bronchoconstriction (and therefore permitting the use of beta-2 adrenergic drugs) in athletes participating in the Beijing Olympic Games.