The use of cytochrome P450 inhibitors in sport. A new generation of doping masking agents?

The activity of the CYP450 enzymes responsible for the phase I metabolism of most of the compounds included in the World Anti-Doping Agency (WADA) list of prohibited substances and methods could be strongly modified by the combined administration of other drugs such as, for example, the antidepressant, the antifungal and the H2 receptor antagonist agents. These compounds act as inhibitors of the CYP450 isoforms and it has been demonstrated that their co-administration with a drug that is also a CYP450 substrate may lead to a substantial alteration of the latter drug bioavailability, metabolism and excretion kinetics. In sports some classes of non-banned drugs, and primarily among them antidepressants, antifungals and the H2 receptor antagonists are extensively used, according to the information available on the doping control forms. Athletes may intentionally combine the CYP450 inhibitors with doping agents to modify in urine the time window of detection of the selected marker(s) of drug abuse, especially in those cases where the parent drugs are extensively metabolized

High levels of osteopontin associated with polymorphisms in its gene are a risk factor for development of autoimmunity/lymphoproliferation

The autoimmune/lymphoproliferative syndrome (ALPS) displays defective function of Fas, autoimmunities, lymphadenopathy/splenomegaly, and expansion of CD4/CD8 double-negative (DN) T cells. Dianzani autoimmune/lymphoproliferative disease (DALD) is an ALPS variant lacking DN cells. Both forms have been ascribed to inherited mutations hitting the Fas system but other factors may be involved. A pilot cDNA array analysis on a DALD patient detected overexpression of the cytokine osteopontin (OPN). This observation was confirmed by enzyme-linked immunosorbent assay (ELISA) detection of higher OPN serum levels in DALD patients (n = 25) than in controls (n = 50). Analysis of the OPN cDNA identified 4 polymorphisms forming 3 haplotypes (A, B, and C). Their overall distribution and genotypic combinations were different in patients (N = 26) and controls (N = 158) (P <.01). Subjects carrying haplotype B and/or C had an 8-fold higher risk of developing DALD than haplotype A homozygotes. Several data suggest that these haplotypes influence OPN levels: (1) in DALD families, high levels cosegregated with haplotype B or C; (2) in healthy controls, haplotype B or C carriers displayed higher levels than haplotype A homozygotes; and (3) in AB and AC heterozygotes, mRNA for haplotype B or C was more abundant than that for haplotype A. In vitro, exogenous OPN decreased activation-induced T-cell death, which suggests that high OPN levels are involved in the apoptosis defect

Part 2. Comparison of emergency washing solutions in 70% hydrofluoric acid-burned human skin in an established ex vivo explants model

Background: Hydrofluoric acid (HF) is a small and partially dissociated acid (pKa 3.2), able to deeply penetrate into human skin in addition to the corrosiveness of the hydrogen ion (H+) and the toxicity of the fluoride ion (F-). However, there has been a lack of experimental studies to objectively characterize the results of human HF skin exposure decontamination