1. The thrombin receptor (the protease-activated receptor-1; PAR-1) is located on vascular cells as well as platelets and may play important roles in atherosclerotic disorders, such as coronary artery diseases (CAD). In the present study, we searched for genetic polymorphisms of the PAR-1 gene and evaluated their effects on CAD by association analysis. 2. We identified six polymorphisms in the 5'-untranslated region of the PAR-1 gene by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP); five single-nucleotide polymorphisms (SNP) at -2355 (A to G), -2333 (T to G), -1428 (G to A), -1071 (C to T) and -561 (A to G) and a simple sequence repeat (SSR) polymorphism between -1935 and -1841. Five SNP were in strong linkage disequilibrium with each other to make three major haplotypes, the frequency of which was over 90% of all possible haplotypes. 3. For association analysis, 150 patients who had CAD (CAD+), 58 subjects who had no stenosis on the coronary angiogram and 186 reference subjects who had no clinical evidence of CAD were used from the Korean population. The genotype frequencies of the SNP were in Hardy-Weinberg equilibrium, except A-561G in CAD+. The association of these SNP as well as of the SSR with CAD was not evident. This result suggests no major roles of the PAR-1 gene in CAD in Koreans.
OBJECTIVES: Compare costs associated with treatment for acute or degenerative medial meniscus tears. METHODS: Prospective, non-randomized, open-label, 24month observational surveillance study conducted between January 2011 and December 2014 at a single institution, approved by hospital Institutional Review Board, and with patient informed consent. Patients (n¼50) initiated into conservative (non-surgical) therapy or a surgical partial meniscectomy based on clinical assessment following physical examination and MRI analysis by the study investigator. Cumulative treatment costs were compared at 24 months for patients in three distinct treatment pathways during the observation time period: Group 1) conservative (non-surgical) therapy; Group 2) one or more surgical interventions without knee arthroplasty; Group 3) one or more surgical interventions with knee arthroplasty. Costs were calculated using billing record reimbursements for all services directly administered by the treating institution, and imputed for all services prescribed by investigator but provided external to the treating institution. RESULTS: At initiation, 33 patients (67%) were prescribed conservative care, and 17 patients (33%) were prescribed a partial meniscectomy. By 24 months, 26 patients (52%) remained in Group 1, 22 patients (44%) were in Group 2, and 2 patients (4%) transitioned to Group 3.
BackgroundInflammasomes are cytoplasmic multiprotein complexes that recognise various exogenous and endogenous danger signals in myeloid cells, particularly macrophages. Inflammasome activation eventually induces inflammatory responses in macrophages by activating gasdermin-d-mediated pyroptosis and the secretion of pro-inflammatory cytokines including interleukin (IL)−1β and IL-18 in a caspase-1-dependent manner. The production of IL-1 has been found to be highly induced in AS1 and caspase-1 level was significantly elevated in spondyloarthritis patients than in those with other arthritic diseases,2 suggesting the possibility that inflammasomes might be involved in pathogenesis of ankylosing spondylitis (AS). However, few studies have addressedd the roles of inflammasomes in AS.ObjectivesThis study was performed to investigate the role of NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome in the peripheral blood mononuclear cells (PBMCs) from AS patients.MethodsPBMCs from 11 patients and 9 healthy controls were isolated and mRNA expression levels of NLRP3 inflammasome, pro-IL-1β, IL-1β, pro-caspase-1, and caspase-1 were determined using quantitative real-time PCR. IL-17A (100 ng/mL) was added to the cell cultures, then, cytokine expression, signalling pathways, and inflammasome machinery are determined using real-time RT-PCR and Western blot. After transfection of siNLRP3 to AS PBMCs, mRNA and proteins levels of IL-1β and caspase-1 were determined using real time PCR and western blot.ResultsExpressions of NLRP3, IL-1β, and caspase-1 mRNAs, but not IL-18, were increased in PBMCs from AS patients compared to controls. Incubation of AS PBMCs with IL-17A significantly increased NLRP3, IL-1β, IL-18, and caspase-1 expressions in AS PBMCs. Western blot showed IL-17A treatment induced the phosphorylation of Akt, p38 MAPK, and NF-κB p65 in AS PBMCs. Down-regulation of NLRP3 by transfection of siRNA decreased mRNA expressions and productions of IL-1β and caspase-1 in AS PBMCs.ConclusionsActivity of NLRP3 inflammasome was increased in AS patients and IL-17A potentiated the activation of NLRP3 inflammasome. Our data suggest the possible role of NLRP3 inflammasome in inflammatory response in AS.References[1] Tan AL, Marzo-Ortega H, O’Connor P, Fraser A, Emery P, McGonagle D. Efficacy of anakinra in active ankylosing spondylitis: a clinical and magnetic resonance imaging study. Ann Rheum Dis. 2004;63:1041–1045.[2] Son CN, Bang SY, Kim JH, Choi CB, Kim TH, Jun JB. Caspase-1 level in synovial fluid is high in patients with spondyloarthropathy but not in patients with gout. J Korean Med Sci. 2013;28:1289–1292.Disclosure of InterestNone declared
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