Cigarette smoke condensate extracts augment collagen-induced arthritis in mice

Although cigarette smoking is a solid environmental risk factor for rheumatoid arthritis (RA) as revealed by epidemiological studies, the scientific basis has not been provided. Proinflammatory cytokines produced by synoviocytes are implicated in the pathogenesis of RA. As cigarette smoke condensate (CSC) is able to up-regulate the production of proinflammatory cytokines from human fibroblast-like synoviocytes, we studied the effect of CSC on induction of arthritis in the mouse model of collagen type II-induced arthritis (CIA). When mainstream CSC or sidestream CSC was administered into DBA/1J mice at the time of immunization with collagen and complete Freund adjuvant, CSC dose-dependently augmented the induction and clinical development of arthritis at both young and older mice. Peritoneal injected mainstream CSC one day before immunization also exhibited the augmenting effect, suggesting the systemic effect of CSC. These results support the etiological role of cigarette smoking in RA.     

Role of cyclooxygenase-2, but not cyclooxygenase-1, on type II collagen-induced arthritis in DBA/1J mice

The purpose of this paper is to explore the contribution of isoforms of cyclooxygenase (COX) to chronic inflammation in DBA/1J mice with type II collagen-induced arthritis (CIA). To address this question pharmacologically, we tested the effects of selective inhibitors of COX-1 and COX-2 on paw edema and the formation of arachidonic acid metabolites in the inflamed paws immunized with type II collagen (CII). Oral administration of FR140423 (3-(difluoromethyl)-1-(4-methoxyphenyl)-5-[4-(methylsulfinyl)phenyl]pyrazole), a selective inhibitor of COX-2, showed a dose-dependent anti-inflammatory effect in mouse CIA with ED(50) value of 0.20mg/kg. Indomethacin, a non-selective inhibitor of COX, also inhibited paw edema in this arthritic model. In contrast, the selective COX-1 inhibitors, FR122047 (1-[(4,5-bis(4-methoxyphenyl)-2-thiazoyl)carbonyl]-4-methylpiperazine hydrochloride) and SC-560 (5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethylpyrazole), had no effect in mouse CIA model. The increase of prostaglandin (PG) E(2) and thromboxane (TX) B(2) in the mouse inflamed paws was associated with the development of paw edema induced by CII. FR140423 dose dependently inhibited the levels of PGE(2) and TXB(2) in the CIA mouse paws with ED(50) values of 0.20 and 0.12 mg/kg, respectively, similar to indomethacin. In contrast, FR122047 and SC-560 had no effect. These results suggest that COX-2, but not COX-1, contributes to the edema and the formation of PGE(2) and TXB(2) in mouse CIA model.     

胶原诱导性关节炎大鼠滑膜组织中磷酸化p38与JNK通路及痹肿消汤的影响***

背景：有研究报道滑膜细胞信号传导异常是类风湿关节炎发病的重要机制之一。 目的：观察胶原诱导性关节炎大鼠中丝裂原活化蛋白激酶通路中磷酸化p38和磷酸化JNK的活化及痹肿消汤的影响。方法：将72只SD大鼠随机分为正常组、模型组、痹肿消汤组。模型组及痹肿消汤组大鼠足趾注射胶原蛋白乳剂制备胶原诱导性关节炎模型大鼠,10 d后加强免疫,初次免疫后第14天开始给痹肿消汤组大鼠每天痹肿消汤灌胃,模型组蒸馏水灌胃,正常组自由饮水。 结果与结论：Western blot 检测结果显示,胶原诱导性关节炎大鼠中磷酸化p38及JNK的表达较正常组显著增高(P < 0.05)。与模型组相比,痹肿消汤组能下调磷酸化p38及JNK蛋白的表达(P < 0.05)。说明痹肿消汤可抑制类风湿关节炎中磷酸化p38及JNK的高表达。     

A Decade of Outcomes and Predictors of Sac Enlargement after Endovascular Abdominal Aortic Aneurysm Repair Using Zenith Endografts in a Japanese Population

PurposeTo present 10-year outcomes and risk factors for sac enlargement after endovascular aneurysm repair (EVAR) using the Zenith AAA Endovascular Graft (Cook, Inc, Bloomington, Indiana) in a Japanese population.Material and MethodsDuring the period 1999–2011, 127 patients underwent elective EVAR using Zenith endografts at a single institution. A retrospective investigation looked at initial rates of technical success and complications, 10-year rate of freedom from all-cause and aneurysm-related mortality, freedom from secondary intervention and sac enlargement, and risk factors for second intervention and sac enlargement.ResultsThe median age of the patients was 78 years, and the median follow-up time was 43 months. The initial technical success rate was 98.4% (125 of 127 patients). Major adverse events occurred in 7 of 127 (5.5%) patients. Rates of freedom from all-cause and aneurysm-related mortality at 1, 3, 5, and 10 years were 95%, 87%, 77%, and 39% (all-cause mortality) and 100%, 100%, 99%, and 93% (aneurysm-related mortality). Rates of freedom from secondary intervention at 1, 3, 5, and 10 years were 97%, 91%, 88%, and 70%. Rates of primary freedom from sac enlargement at 1, 3, 5, and 10 years were 99%, 87%, 75%, and 67%. Multivariate analysis revealed aneurysm sac diameter as an independent risk factor for a secondary intervention. Preoperative sac diameter combined with an angulated short (AS) proximal neck was a risk factor for sac enlargement.ConclusionsThe 10-year results of EVAR using Zenith endografts in a Japanese population were comparable to results from Western countries. Larger aneurysms and AS neck were predictors of sac enlargement after EVAR.     

丙酮酸乙酯对胶原诱导性关节炎大鼠的治疗作用

目的探讨丙酮酸乙酯（EP）在胶原诱导关节炎（CIA）大鼠模型中的治疗作用和安全性。方法利用牛Ⅱ型胶原建立Wistar大鼠CIA模型,随机分为CIA对照组和EP干预组,并设立正常对照组。每周观察各组大鼠的一般情况变化,并对双后足进行关节炎指数（AI）评分及测量后足容积;在实验第42、63天分别对各组大鼠的右后足进行放射学及病理学观察。结果 CIA对照组大鼠与正常对照组大鼠比较,有脱毛、精神萎靡,摄食及其他活动减少;EP干预组大鼠精神食欲尚可。体重变化,与正常对照组大鼠比较,CIA对照组大鼠从造模第28天开始,体重增加缓慢;EP干预组从造模第35天开始体重增加程度也有所下降,差异均有统计学意义（P〈0.05）;从造模第56天开始EP干预组体重增加明显,与正常组比较差异无统计学意义（P〉0.05）。关节炎症,EP干预组大鼠造模第28、42、63天AI值分别为3.83±0.71、3.42±0.79、1.50±0.54,明显低于同期CIA对照组AI值4.58±1.08、5.17±1.19、3.67±0.81,差异均有统计学意义（P〈0.05）。足肿胀度,EP干预组大鼠足肿胀度在造模第42、63天分别为（1.58±0.11）、（1.51±0.09）ml,低于CIA对照组足肿胀度（1.97±0.10）、（1.81±0.10）ml,差异均有统计学意义（P〈0.05）。影象学表现,CIA对照组X线示关节间隙消失,严重的可出现骨质破坏、融合;与CIA对照组相比,EP干预组仅可见部分关节有关节间隙模糊、骨质疏松,很少见关节破坏融合。病理学表现,CIA对照组滑膜肥厚,大量炎性细胞浸润,并有骨结构破坏;与CIA对照组相比,EP干预组滑膜细胞增生不明显,有少量炎性细胞浸润,关节软骨和骨组织破坏不明显。EP干预过程中未见明显不良反应。结论 EP能改善CIA大鼠关节炎症状、放射学及滑膜组织病理变化,起到抑制炎症的作用,且安全性好。     

加味犀角地黄汤对大鼠CIA急性关节肿胀与滑膜组织中VEGF表达的影响

目的 通过测定大鼠关节滑膜组织中血管内皮生长因子(VEGF)在大鼠胶原诱导性关节炎(CIA)模型形成及应用加味犀角地黄汤(XDD)治疗过程中的表达水平,探讨加味XDD对类风湿关节炎(RA)的治疗作用.方法 用SD大鼠制作Ⅱ型胶原蛋白诱导的CIA大鼠模型,实时荧光定量PCR法检测正常组、模型组和实验组大鼠在第42 d关节...     

Genetic heterogeneity in rheumatoid arthritis mouse models induced by extrinsic and intrinsic factors

A cumulative effect of the susceptibility genes with polymorphic alleles may be responsible for rheumatoid arthritis (RA). The objective of this study was to clarify whether susceptibility to RA is under the control of common allelic loci between two different RA models induced by extrinsic and intrinsic factors, collagen‐induced arthritis (CIA) in DBA/1 mice and arthritis in MRL/Mp (MRL) mice associated with the Fas deficient mutant gene, Fas^lpr, respectively. CIA was examined in mice of parental DBA/1 and MRL, (MRL × DBA/1) F1 and (MRL × DBA/1) F2 progenies. In genome‐wide screening of the severity in the F2 using microsatellite markers, significant linkage was observed on chromosomes 5 and 17 at map position of D5Mit259 and H‐2, respectively, associated with DBA/1 alleles, while there was no loci associated with arthritis of MRL‐Fas^lpr mice previously identified. In a quantitative trait locus (QTL) analysis, the locus on chromosome 5 showed the highest peak at map position 35 cM (LOD score 6.0). This study may indicate that the arthritis induced by extrinsic and intrinsic factors is under the control of a different combination of susceptibility genes with common and different alleles, possibly simulating the genetic heterogeneity of RA.     

Primary Endovascular Elective Repair and Repair of Ruptured Isolated Iliac Artery Aneurysms Is Durable—Results of 72 Consecutive Patients

Purpose

To evaluate outcome of endovascular elective repair and repair of ruptured isolated iliac artery aneurysms (IIAAs) as a primary treatment strategy.

Deacetylase inhibition increases regulatory T cell function and decreases incidence and severity of collagen-induced arthritis

Collagen-induced arthritis (CIA) is an established mouse model of disease with hallmarks of clinical rheumatoid arthritis. Histone/protein deacetylase inhibitors (HDACi) are known to inhibit the pathogenesis of CIA and other models of autoimmune disease, although the mechanisms responsible are unclear. Regulatory T cell (Treg) function is defective in rheumatoid arthritis. FOXP3 proteins in Tregs are present in a dynamic protein complex containing histone acetyltransferase and HDAC enzymes, and FOXP3 itself is acetylated on lysine residues. We therefore investigated the effects of HDACi therapy on regulatory T cell function in the CIA model. Administration of an HDACi, valproic acid (VPA), significantly decreased disease incidence (p < 0.005) and severity (p < 0.03) in CIA. In addition, VPA treatment increased both the suppressive function of CD4⁺CD25⁺ Tregs (p < 0.04) and the numbers of CD25⁺FOXP3⁺ Tregs in vivo. Hence, clinically approved HDACi such as VPA may limit autoimmune disease in vivo through effects on the production and function of FOXP3⁺ Treg cells.