Baseline vWF factor predicts the development of elevated pulmonary artery pressure in systemic sclerosis

Objectives. This study aims to examine the utility of von Willebrand factor (vWF) as a biomarker in lcSSc, in particular the ability of vWF to predict the future development of disease manifestations in this disease. Methods. vWFAg concentrations were measured in the serum of patients with lcSSc at baseline and at 3 years, during the QUINs trial [Prevention of Vascular Damage in Scleroderma with Angiotensin-Converting Enzyme (ACE) Inhibition]. %DL(CO), %KCO, %FVC, pulmonary artery pressure (PAP) estimation by echocardiography, Raynaud's attack frequency, Raynaud's severity, digital ulcer frequency, urinary protein excretion, estimated glomerular filtration rate (eGFR), modified Rodnan skin score and Medsger disease activity score were also measured at baseline and 3 years. Results. Baseline serum vWF concentrations were related to concurrent Medsger disease activity score, %DL(CO), %FVC, urinary protein excretion, eGFR and PAP >30?mmHg. In logistic regression models, baseline serum vWF concentrations were able to predict the future development of elevated PAP by echocardiography (PAP >40?mmHg, P?=?0.001). Conclusions. Pulmonary artery hypertension is a life-threatening complication of lcSSc. vWF is a marker of endothelial cell activation. Raised serum concentrations of vWF in lcSSc increase the risk of developing subsequent elevation in PAP. Therefore screening patients with lcSSc for vWF may identify a group at risk of developing PAH. These patients could potentially be targeted with agents that stabilize the endothelium, e.g. statins.     

明胶改性壳聚糖纤维表征及其体内降解特点

目的：采用明胶处理壳聚糖纤维,考察其表征及在大鼠肌袋内的生物相容性.方法：实验于2006-09/2007-01在解放军第八十九医院全军创伤骨科研究所实验室完成.①实验分组：分别以磷酸盐缓冲液、50,100 g/L明胶处理壳聚糖纤维.②实验评估：测定壳聚糖纤维膨胀率、拉伸强度;扫描电镜、红外光谱观察壳聚糖纤维的形态及结构;分离大鼠脊柱两侧椎旁肌肉形成3个肌袋,分别植入经γ射线灭菌的3种纤维20 mg.术后1周,1,3个月将纤维连同包膜完整取出,计算体内降解率.另取标本连同周围肌肉行苏木精-伊红染色. 结果：①壳聚糖纤维的膨胀率及拉伸强度：磷酸盐缓冲液组纤维膨胀率最高,拉伸强度最小;100 g/L明胶组膨胀率最低,拉伸强度最大.100 g/L明胶组拉伸强度与磷酸盐缓冲液组和50 g/L明胶组间差异有显著性意义（P＜0.05）,3组壳聚糖纤维膨胀率差异无显著性意义.②壳聚糖纤维的形态和结构：扫描电镜下磷酸盐缓冲液组纤维束交织,结构略显松散,50、100 g/L明胶改性后纤维结构更为致密.红外光谱分析显示明胶和壳聚糖间有相互作用.③体内降解率：磷酸盐缓冲液组体内平均降解率65%,50,100 g/L明胶组平均降解率分别为78%和81%,3组间差异无显著性意义.④壳聚糖纤维植入肌袋后的组织相容性：改性后壳聚糖纤维植入后与大鼠周围肌肉连接紧密,表面包膜薄,细胞主要为淋巴细胞,植入12周后3组纤维大部分吸收. 结论：明胶改性可进一步提高壳聚糖纤维的强度和生物相容性.     

外源性一氧化氮对创伤愈合过程中一氧化氮合酶表达及瘢痕形成的影响

目的:应用组织化学、免疫组织化学及计算机辅助图像分析方法,观察外源性一氧化氮在创伤愈合过程不同时间,对一氧化氮合酶表达和胶原形成的影响,探讨其在促进创伤愈合和抑制病理性瘢痕形成中的机制。方法:实验于2004-09/2006-03在河北省人民医院整形烧伤外科及河北省人民医院临床医学研究中心完成。以硝普钠为一氧化氮供体,将60只大鼠随机分为对照组及硝普钠0.5,1,2,4mmol/L组,每组12只,通过建立大鼠创伤模型,并分别在创面局部应用50g/L葡萄糖溶液、0.5,1,2,4mmol/L硝普钠,观察及测量创伤后3,7,10,14d的肉芽组织生长情况、一氧化氮合酶的表达情况和肉芽组织中羟脯氨酸含量。结果:60只大鼠全部进入结果分析。①形态学观察:对照组于创伤后14d可完全愈合;硝普钠0.5mmoL/L组及1mmoL/L组肉芽组织生长良好,且愈合时间较对照组提前三四天;硝普钠2mmoL/L组及4mmoL/L组愈合情况不良,完全愈合时间延迟,皮肤张力较低,炎症反应明显。②一氧化氮合酶蛋白表达:大鼠皮肤创伤后角质形成细胞、汗腺、毛囊和骨骼肌细胞以及创伤后肉芽组织的炎症细胞、成纤维细胞、血管内皮细胞均不同程度的表达一氧化氮合酶蛋白。对照组在第3天和第14天分别呈现一氧化氮合酶阳性颗粒表达高峰,而硝普钠各组仅在第7～10天出现表达一氧化氮合酶阳性高峰,呈先增加后减少的趋势。③羟脯氨酸含量:对照组从创伤后第3,7,10,14天羟脯氨酸含量进行性增加[依次为(1.637±0.127),(2.250±0.169),(2.420±0.201),(2.908±0.241)mg/g];硝普钠0.5mmol/L组在创伤后第3,7天羟脯氨酸含量低于对照组[(1.435±0.147),(1.766±0.211)mg/g,P<0.05或P<0.01],而在第10天和第14天羟脯氨酸含量均高于对照组[(3.128±0.240),(3.437±0.239)mg/g,P<0.01];硝普钠1mmol/L组和2mmol/L组在第10天和第14天的羟脯氨酸含量明显高于对照组[(1mmol/L组:(3.244±0.245)(3.582±0.282)mg/g,P<0.01;硝普钠2mmol/L组:(3.666±0.263),(4.301±0.268)mg/g,P<0.01);硝普钠4mmol/L组仅在创伤后第3天表现比对照组多[(1.912±0.139)mg/g,P<0.01),其余均与对照组水平相近。结论:局部应用外源性一氧化氮具有显著的促修复作用,主要体现在伤后第7～10天,小剂量的一氧化氮促进创面愈合的作用远远大于大剂量一氧化氮。     

Steroids, non-steroidal anti-inflammatory drugs, and sigmoid diverticular abscess perforation in rheumatic conditions

BACKGROUND: Corticosteroids and non-steroidal anti-inflammatory drugs are widely used for the treatment of rheumatic conditions, but their gastrointestinal damage significantly limits their use. Sigmoid diverticular abscess perforation (SDAP) is a very serious complication of diverticular disease. OBJECTIVE: To determine the aetiology of large bowel SDAP in rheumatic conditions. METHODS: 64 patients with SPAD and 320 controls from a similar geographical area and of similar socioeconomic status were studied. RESULTS: The results showed that independently of rheumatic diagnosis corticosteroid treatment is strongly associated with SDAP (OR 31.9 (95% CI 6.4 to 159.2; p<0.001), and non-steroidal anti-inflammatory drugs only weakly associated (OR 1.8 (95% CI 0.96 to 3.4); p = 0.069). A rheumatic diagnosis is also strongly associated with the development of SDAP (OR 3.5 (95% CI 1.9 to 6.7); p<0.001). CONCLUSIONS: SDAP has serious implications for patients and consumes many healthcare resources. Patients and physicians should be warned of this potential complication.     

Microalbuminuria: is it a predictor of ischaemic heart disease in rheumatoid arthritis?

SIR, We read with interest the article by Kitas and Erb [1],where an interesting parallel is drawn between rheumatoid arthritis(RA) and type-2 diabetes (T2D) with respect to ischaemic heartdisease (IHD). The association between RA and IHD, as with T2D,is clearly important, yet in the     

Methotrexate reduces inflammatory cell numbers, expression of monokines and of adhesion molecules in synovial tissue of patients with rheumatoid arthritis

Methotrexate (MTX) is one of the most widely prescribed drugs in the treatment of rheumatoid arthritis (RA). The mechanism by which MTX exerts its anti-rheumatic effect has not yet been defined. The aim of the present study was to investigate the effect of MTX treatment (7.5- 15 mg/week) on synovial tissue in RA. For this purpose, synovial biopsies were taken from 11 RA patients before and 16 weeks after initiation of MTX therapy. Immunohistochemistry was performed using monoclonal antibodies (MAb) specific for CD3, CD4, CD8, CD22, CD25, CD38, CD68, MAb67, Ki67, interferon gamma (IFN-gamma), interleukin (IL)- 1alpha, IL-1beta, tumour necrosis factor alpha (TNF-alpha), E-selectin, ICAM-1 and VCAM-1. All parameters for disease activity improved during the period of treatment. Immunohistochemical analysis revealed a statistically significant decrease in scores for CD3, CD8, CD38, CD68, Ki67, IL-1beta, TNF-alpha and the adhesion molecules E-selectin and VCAM-1. The observed decrease in synovial scores for inflammatory cells, monokines and adhesion molecules suggests that the anti- inflammatory effect of MTX is, in part, dependent on a reduction in monokine-inducible vascular adhesion molecules and subsequent reduction of cell traffic into joints.