Genetic variation in CFH predicts phenytoin-induced maculopapular exanthema in European-descent patients

Objective To characterize, among European and Han Chinese populations, the genetic predictors of maculopapular exanthema (MPE), a cutaneous adverse drug reaction common to antiepileptic drugs. Methods We conducted a case-control genome-wide association study of autosomal genotypes, including Class I and II human leukocyte antigen (HLA) alleles, in 323 cases and 1,321 drug-tolerant controls from epilepsy cohorts of northern European and Han Chinese descent. Results from each cohort were meta-analyzed. Results We report an association between a rare variant in the complement factor H–related 4 (CFHR4) gene and phenytoin-induced MPE in Europeans (p = 4.5 × 10–11; odds ratio [95% confidence interval] 7 [3.2–16]). This variant is in complete linkage disequilibrium with a missense variant (N1050Y) in the complement factor H (CFH) gene. In addition, our results reinforce the association between HLA-A*31:01 and carbamazepine hypersensitivity. We did not identify significant genetic associations with MPE among Han Chinese patients. Conclusions The identification of genetic predictors of MPE in CFHR4 and CFH, members of the complement factor H–related protein family, suggest a new link between regulation of the complement system alternative pathway and phenytoin-induced hypersensitivity in European-ancestral patients

Heat acclimation improves intermittent sprinting in the heat but additional pre-cooling offers no further ergogenic effect

The aim of this study was to determine the effect of 10 days of heat acclimation with and without pre-cooling on intermittent sprint exercise performance in the heat. Eight males completed three intermittent cycling sprint protocols before and after 10 days of heat acclimation. Before acclimation, one sprint protocol was conducted in control conditions (21.8 ± 2.2°C, 42.8 ± 6.7% relative humidity) and two sprint protocols in hot, humid conditions (33.3 ± 0.6°C, 52.2 ± 6.8% relative humidity) in a randomized order. One hot, humid condition was preceded by 20 min of thigh pre-cooling with ice packs (−16.2 ± 4.5°C). After heat acclimation, the two hot, humid sprint protocols were repeated. Before heat acclimation, peak power output declined in the heat (P < 0.05) but pre-cooling prevented this. Ten days of heat acclimation reduced resting rectal temperature from 37.8 ± 0.3°C to 37.4 ± 0.3°C (P < 0.01). When acclimated, peak power output increased by 2% (P < 0.05, main effect) and no reductions in individual sprint peak power output were observed. Additional pre-cooling offered no further ergogenic effect. Unacclimated athletes competing in the heat should pre-cool to prevent reductions in peak power output, but heat acclimate for an increased peak power output

Intermittent exercise with and without hypoxia improves insulin sensitivity in individuals with type 2 diabetes

Context: Hypoxia and muscle contraction stimulate glucose transport activity in vitro. Exercise and hypoxia have additive effects on insulin sensitivity in type 2 diabetics (T2D). Objective: The objective of the study was to examine the effectiveness of intermittent exercise with and without hypoxia on acute- and moderate-term glucose kinetics and insulin sensitivity in T2D. Setting: The study was conducted at a university research center. Design, Participants, and Interventions: Eight male T2D patients completed the following: 1) 60 min of continuous exercise at 90% lactate threshold in hypoxia (HyEx60); 2) intermittent exercise at 120% lactate threshold, separated by periods of passive recovery (5:5 min) in hypoxia [Hy5:5; O2 ∼ 14.7 (0.2)%]; and 3) intermittent exercise (5:5 min) at 120% lactate threshold in normoxia (O2 ∼ 20.93%). Main Outcome Measures: Glucose appearance and glucose disappearance, using an adapted non-steady-state one-compartment model were measured. Homeostasis models of insulin resistance (HOMAIR), fasting insulin resistance index (FIRI), and β-cell function were calculated 24 and 48 h after exercise conditions. Results: Glucose disappearance increased from baseline (1.85 mg/kg · min−1) compared with 24 h (2.01 min/kg · min−1) after HyEx60 (P = 0.031). No difference was noted for both Hy5:5 (P = 0.064) and normoxia (P = 0.385). Hy5:5 demonstrated improvements in HOMAIR from baseline [d 1, 6.20 (0.40)] when comparisons were made with d 2 [4.83 (0.41)] (P = 0.0013). HOMAIR and FIRI improved in the 24 h (HOMAIR, P = 0.002; FIRI, P = 0.003), remaining reduced 48 h after HyEx60 (HOMAIR, P = 0.028; and FIRI, P = 0.034). Conclusion: HyEx60 offered the greatest improvements in acute and moderate-term glucose control in T2D. Intermittent exercise stimulated glucose disposal and improved after exercise insulin resistance, which was enhanced when exercise was combined with hypoxia (Hy5:5). The data suggest a use of hypoxic exercise in treatment of T2D