RESUMO
This systematic review and meta-analysis assesses the effectiveness of no or low-dose versus high-dose aspirin on the incidence of coronary artery aneurysms (CAAs), intravenous immunoglobulin (IVIG) resistance, hospital stay length, and fever duration during the acute phase of Kawasaki disease. Our review adheres to the Preferred Reporting Items for Systematic Reviews guidelines. The PubMed and Google Scholar databases were comprehensively searched to identify relevant studies in the literature, including observational studies and randomized controlled trials (RCTs). The primary outcome was the incidence of CAAs. The secondary outcomes were the hospital stay length, fever duration, and IVIG resistance. The risk of bias was assessed using the Newcastle-Ottawa scale for cohort studies and Cochrane's Risk of Bias Tool for RCTs. The data were analyzed using the Review Manager software. Twelve studies with a total of 68,495 participants met the inclusion criteria. The incidences of CAAs (odds ratio [OR] = 0.93; 95% confidence interval [CI] = 0.64-1.34) and IVIG resistance (OR = 1.46; 95% CI = 1.00-2.12) did not differ significantly between no or low-dose versus high-dose aspirin in treating acute KD. Moreover, the fever durations (mean difference [MD] = 3.55 h; 95% CI = -7.99-15.10) and hospital stay lengths (MD = -0.54 days; 95% CI = -2.50-1.41) were similar in the no and low-dose aspirin group compared to the high-dose aspirin group. Our review indicates that there are no significant differences in the incidences of CAA and IVIG resistance, fever durations, and hospital stay lengths between no or low-dose versus high-dose aspirin in treating the acute phase of KD.
RESUMO
Glycine receptors (GlyR) belong to the pentameric ligand-gated ion channel (pLGIC) superfamily and mediate fast inhibitory transmission in the vertebrate CNS. Disruption of glycinergic transmission by inherited mutations produces startle disease in man. Many startle mutations are in GlyRs and provide useful clues to the function of the channel domains. E103K is one of few startle mutations found in the extracellular agonist binding site of the channel, in loop A of the principal side of the subunit interface. Homology modeling shows that the side chain of Glu-103 is close to that of Arg-131, in loop E of the complementary side of the binding site, and may form a salt bridge at the back of the binding site, constraining its size. We investigated this hypothesis in recombinant human α1 GlyR by site-directed mutagenesis and functional measurements of agonist efficacy and potency by whole cell patch clamp and single channel recording. Despite its position near the binding site, E103K causes hyperekplexia by impairing the efficacy of glycine, its ability to gate the channel once bound, which is very high in wild type GlyR. Mutating Glu-103 and Arg-131 caused various degrees of loss-of-function in the action of glycine, whereas mutations in Arg-131 enhanced the efficacy of the slightly bigger partial agonist sarcosine (N-methylglycine). The effects of the single charge-swapping mutations of these two residues were largely rescued in the double mutant, supporting the possibility that they interact via a salt bridge that normally constrains the efficacy of larger agonist molecules.
