However, whether IL6R blockade also reduces risk of coronary heart disease is unknown.
Methods Applying the mendelian
randomisation principle, we used single nucleotide polymorphisms (SNPs) in the gene IL6R to evaluate the likely efficacy and safety of IL6R inhibition for primary prevention of coronary heart disease. We compared genetic findings with the effects of tocilizumab reported in randomised trials in patients with rheumatoid arthritis.
Findings In 40 studies including up to 133 449 individuals, selleck inhibitor an IL6R SNP (rs7529229) marking a non-synonymous IL6R variant (rs8192284; p.Asp358Ala) was associated with increased circulating log interleukin-6 concentration (increase per allele 9.45%, 95% CI 8.34-10.57) as well as reduced C-reactive protein (decrease per allele 8.35%, 95% CI 7.31-9.38) and fibrinogen concentrations (decrease per allele 0.85%, 95% CI 0.60-1.10). This pattern of effects was consistent with IL6R blockade from infusions of tocilizumab (4-8 mg/kg see more every 4 weeks) in patients with rheumatoid arthritis studied in randomised trials. In 25 458 coronary heart disease cases and 100 740 controls, the IL6R rs7529229 SNP was associated with a decreased odds of coronary heart disease events (per allele odds ratio 0.95, 95% CI 0.93-0.97, p=1.53×10(-5)).
Interpretation On the basis of genetic evidence
in human beings, IL6R signalling seems to have a causal role in development of coronary PRN1371 cost heart disease. IL6R blockade could provide a novel therapeutic approach to prevention of coronary heart disease that warrants testing in suitably powered randomised trials. Genetic studies in populations could be used more widely
to help to validate and prioritise novel drug targets or to repurpose existing agents and targets for new therapeutic uses.”
“Illicit gamma-hydroxybutyrate (GHB) has received attention as a “”date rape drug”" that produces robust amnesia; however, there is little experimental evidence in support of GHB’s amnestic effects.
This study compared the cognitive effects of GHB (sodium oxybate) with those of triazolam in healthy volunteers.
Doses of sodium oxybate (1.125, 2.25, and 4.5 g/70 kg), triazolam (0.125, 0.25, and 0.5 mg/70 kg), and placebo were administered to 15 volunteers under repeated measures, counterbalanced, double-blind, double-dummy conditions. The time course and peak physiological, psychomotor, subjective, and cognitive effects were examined.
Sodium oxybate and triazolam produced similar increases in participant ratings of drug effects. Performance on psychomotor, working memory, and episodic memory tasks was impaired to a greater extent after triazolam than sodium oxybate.
Together, these data suggest that sodium oxybate produces less psychomotor and cognitive impairment than triazolam at doses that produce equivalent participant-rated subjective effects in healthy volunteers.