T-cell recognition of chemicals, protein allergens and drugs: towards the development of in vitro assays

Chemicals can elicit T-cell-mediated diseases such as allergic contact dermatitis and adverse drug reactions. Therefore, testing of chemicals, drugs and protein allergens for hazard identification and risk assessment is essential in regulatory toxicology. The seventh amendment of the EU Cosmetics Directive now prohibits the testing of cosmetic ingredients in mice, guinea pigs and other animal species to assess their sensitizing potential. In addition, the EU Chemicals Directive REACh requires the retesting of more than 30,000 chemicals for different toxicological endpoints, including sensitization, requiring vast numbers of animals. Therefore, alternative methods are urgently needed to eventually replace animal testing. Here, we summarize the outcome of an expert meeting in Rome on 7 November 2009 on the development of T-cell-based in vitro assays as tools in immunotoxicology to identify hazardous chemicals and drugs. In addition, we provide an overview of the development of the field over the last two decades

Effects of walking on heart rate recovery, endothelium modulators and quality of life in patients with heart failure

Background: Few studies have addressed the impact of moderate unsupervised everyday physical activity in patients with chronic heart failure (CHF). Design: We investigated the effects of a 12-week walking programme as the sole exercise intervention on heart rate recovery (HRR), index of the autonomic system equilibrium, serum modulators of endothelial function (i.e. asymmetric dimethylarginine (ADMA) and homocysteine), markers of inflammation and oxidative stress and quality of life measures (i.e. SF-36 and the Zung depression scale) in CHF patients. Methods: Twenty-eight stabilized CHF patients of NYHA class II and III volunteered to participate either in the exercise (n=18) or in the non-exercise (n=10) groups. Ten age-matched healthy volunteers provided reference values. The exercise programme consisted of unsupervised 40-minute walking for five days per week. Results: Repeated measures ANOVA revealed significant improvements in HRR (p < 0.001) in the exercise patients compared to their non-exercise counterparts. ADMA levels in CHF patients at baseline were found higher than the healthy reference volunteers (p < 0.03), while a decrease in ADMA levels after walking was associated with HRR changes (r=0.74, p=0.007). Homocysteine levels both at baseline and at the end of the walking intervention decreased in the exercise group, but were still higher than in the healthy individuals. Average walking distance positively correlated with homocysteine decrease (p < 0.05). Total SF-36 score significantly improved (p < 0.02) mainly due to enhancements in the physical component score (p < 0.026). Conclusion: A 12-week unsupervised walking programme exhibits a pronounced HRR amelioration, possibly attenuates endothelial damage and induces a concomitant improvement in perceived quality of life in CHF patients