Stereoselective distribution of tiaprofenic acid in synovium and cartilage in osteoarthritic patients

Objective: In order to document the stereoselective distribution in joints of a chiral nonsteroidal anti-inflammatory drug, the relative affinities of the enantiomers of tiaprofenic acid in synovium and for cartilage were compared. Methods: The distribution of tiaprofenic acid in synovium and in cartilage was studied 25 h after administering the racemic drug for 2 days (600 mg of a sustained-release preparation, once daily), in 12 inpatients with osteoarthritis of the hip requiring arthroplasty. Enantiomers were quantified in plasma and freeze-ground tissues by a chiral HPLC assay. Results: Plasma concentrations of the dextrorotatory (R) enantiomer (0.40 μg/ml) were higher than those of its antipode. The concentration of racemate in synovium (in dried and fresh tissues, 150% and 40%, respectively, of the concentration in plasma) was much higher than that in cartilage (in dried tissues 32% of the plasma concentration). The ratio of the active, dextrorotatory (R) enantiomer to its antipode was higher in synovial tissue than in plasma. Conclusion: Tiaprofenic acid is distributed stereoselectively in plasma and synovium, which contain a higher concentration of the active, dextrorotatory (R) enantiomer. In cartilage, it reaches only a very low concentration. Received: 26 June 1995/Accepted in revised form: 7 November 1995     

雷公藤单体T4对IL-1刺激引起的类风湿患者关节滑膜成纤维细胞增殖和产生IL-6的影响

目的　探讨雷公藤单体 T4对经 IL- 1刺激的体外培养的类风湿关节炎 (RA)患者的关节滑膜成纤维细胞增殖和产生 IL- 6的影响。方法　关节滑膜组织来自行关节置换术或滑膜切除术的类风湿患者。滑膜组织经体外消化使细胞分散后 ,传代培养。以培养 3代后的滑膜成纤维细胞为对象 ,先给予 IL- 1刺激 ,再加入雷公藤 T4单体。结果　 T4可抑制由 IL- 1刺激的滑膜成纤维增殖 ,但不影响 IL- 6的产生。结论　 T4的上述作用可能是其治疗RA的机制之一 ,本研究结果为 T4早日应用于临床治疗 RA提供了一定的理论依据     

Tubulin polymerization‐promoting protein family member 3, Tppp3, is a specific marker of the differentiating tendon sheath and synovial joints

Tppp3, a member of the Tubulin polymerization‐promoting protein family, is an intrinsically unstructured protein that induces tubulin polymerization. We show that Tppp3 is a distinct marker in the developing musculoskeletal system. In tendons, Tppp3 is expressed in cells at the circumference of the developing tendons, likely the progenitors of connective tissues that surround tendons: the tendon sheath, epitenon, and paratenon. These tissues form an elastic sleeve around tendons and provide lubrication to minimize friction between tendons and surrounding tissues. Tppp3 is the first molecular marker of the tendon sheath, opening the door for direct examination of these tissues. Tppp3 is also expressed in forming synovial joints. The onset of Tppp3 expression in joints coincides with cavitation, representing a molecular marker that can be used to indicate this stage in joint transition in joint differentiation. In late embryonic stages, Tppp3 expression highlights other demarcation lines that surround differentiating tissues in the forelimb. Developmental Dynamics 238:685–692, 2009. © 2009 Wiley‐Liss, Inc.     

内镜下手术治疗腕管综合征的应用分析

目的探讨内镜下手术治疗伴有滑膜增生腕管综合征(CTS)的临床疗效。方法回顾性分析在该院手术治疗的37例(41腕)伴有腱周滑膜组织增生的CTS患者,术中均在内镜下切断腕横韧带,同时经内镜入口切除指浅屈肌腱周围增生的滑膜。比较患者手术前后临床症状、体征改变,统计术后优良率。结果按Kelly分级,术后整体优良率为95.12%。夜间麻醒症状均消失,Tinel征、Phalen征阳性率降低至2.44%(P0.05),两点辨别觉平均值低至(3.5±0.9)mm(P0.05),无严重并发症。结论对于伴有腕管内滑膜轻度增生的特发性CTS患者,内镜下腕横韧带切开联合滑膜组织切除,是一种新的、可行的、近期疗效显著的治疗方式,值得临床推广。     

The peridural membrane of the spine has characteristics of synovium

The peridural membrane (PDM) is a well-defined structure between dura mater and the wall of the spinal canal. The spine may be viewed as a multi-segmented joint, with the epidural cavity and neural foramina as joint spaces and PDM as synovial lining. The objective of this investigation was to determine if PDM has histological characteristics of synovium. Samples of the PDM of the thoraco-lumbar spine were taken from 23 human cadavers and analyzed with conventional light microscopy and confocal microscopy. Results were compared to reports on similar analyses of synovium in the literature. Histological distribution of areolar, fibrous, and adipose connective tissue in PDM was similar to synovium. The PDM has an intima and sub-intima. No basement membrane was identified. CD68, a marker for macrophage-like-synoviocytes, and CD55, a marker for fibroblast-like synoviocytes, were seen in the lining and sub-lining of the PDM. Multifunctional hyaluronan receptor CD44 and hyaluronic acid synthetase 2 marker HAS2 were abundantly present throughout the membrane. Marked presence of CD44, CD55, and HAS2 in the well-developed tunica muscularis of blood vessels and in the body of the PDM suggests a role in the maintenance and lubrication of the epidural cavity and neural foramina. Presence of CD68, CD55, and CD44 suggests a scavenging function and a role in the inflammatory response to noxious stimuli. Thus, the human PDM has histological and immunohistochemical characteristics of synovium. This suggests that the PDM may be important for the homeostasis of the flexible spine and the neural structures it contains.     

Fibronectin splice variation in human knee cartilage,meniscus and synovial membrane: Observations in osteoarthritic knee

Fibronectin (FN) is a widely expressed molecule that can participate in development of osteoarthritis (OA) affecting cartilage, meniscus, and synovial membrane (SM). The alternatively spliced isoforms of FN in joint tissues other than cartilage have not been extensively studied previously. The present study compares FN splice variation in patients with varying degrees of osteoarthritic change. Joint tissues were collected from asymptomatic donors and patients undergoing arthroscopic procedures. Total RNA was amplified by PCR using primers flanking alternatively spliced Extra Domain A (EDA), Extra Domain B (EDB) and Variable (V) regions. EDB⁺, EDB^? and EDA^? and V⁺ variants were present in all joint tissues, while the EDA⁺ variant was rarely detected. Expression levels of EDB⁺ and EDV⁺ variants were similar in cartilage, synovium, and meniscal tissues. Synovial expression of V⁺ FN in arthroscopy patients varied with degree of cartilage degeneration. Two V^? isoforms, previously identified in cartilage, were also present in SM and meniscus. Fibronectin splicing in meniscus and SM bears striking resemblance to that of cartilage. Expression levels of synovial V⁺ FN varied with degree of cartilage degeneration. V⁺ FN should be investigated as a potential biomarker of disease stage or progression in larger populations. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:556–562, 2015.

     

A comparative phenotypical analysis of rheumatoid nodules and rheumatoid synovium with special reference to adhesion molecules and activation markers

OBJECTIVES—(1)To analyse the in situ expression of adhesion molecules in rheumatoid nodules. (2) To compare the endothelial expression of adhesion molecules in synovial tissue and subcutaneous nodules obtained from the same patients. (3) To compare the expression of adhesion molecules and activation markers on T cell lines from nodules and synovium.
METHODS—(1) Immunohistochemical analysis by APAAP technique of E selectin, CD44, ICAM-1, PECAM-1, and VCAM-1 was performed on 10 rheumatoid nodules from seven patients with rheumatoid arthritis (RA); nodules and synovium were simultaneously analysed from three patients. (2) T cell lines were generated from RA nodules (n=7) and synovium (n=7) by interleukin 2 expansion, and subsequently characterised by flow cytometry for surface expression of αEβ7, α4β7, CD44, L selectin, LFA-1a, PECAM-1, and CD30.
RESULTS—(1) In rheumatoid nodules, the palisading layer strongly stains for ICAM-1 and PECAM-1, but less pronounced for CD44. VCAM-1 staining was usually negative. ICAM-1 is upregulated in the vessels surrounding the central zone of fibrinoid necrosis. The immunohistological picture in different nodules derived from the same patient was similar. (2) The endothelial expression of adhesion molecules is comparable in RA nodules and synovium on an individual level, except for E selectin, which is overexpressed in nodule endothelium. (3) T cell lines from nodules and synovium display similar adhesion molecule profiles. However, the expression of CD30, a T cell activation marker linked with Th2 subsets, is higher in nodules compared with synovium.
CONCLUSION—These data support a recirculation hypothesis of T cells between articular and extra-articular manifestations in RA, although the activation state of the T cells in each of these localisations may differ.

Keywords: T cells; adhesion molecules; rheumatoid nodules; rheumatoid synovium     

Exploration of the pathogenesis of haemophilic joint arthropathy: understanding implications for optimal clinical management

Haemophilia is an inherited disorder of clotting factor deficiencies resulting in musculoskeletal bleeding, including haemarthroses, leading to orthopaedic complications. The pathogenesis of haemophilic joint arthropathy continues to be explored and there is evidence to suggest that iron, cytokines, and neo angiogenesis can initiate synovial and early cartilage damage resulting in molecular changes and the perpetuation of a chronic inflammatory state. This joint arthropathy has long term consequences for bone health resulting in chronic pain and quality of life issues in the individual with haemophilia. Haemarthroses can be prevented by the administration of clotting factor concentrates (prophylaxis). However, high costs and the need for venous access devices in younger children continue to complicate recommendations for universal prophylaxis. In patients who fail or refuse prophylaxis, procedures, such as synovectomy and arthroplasty, can provide relief from repeated haemarthroses. The optimal timing of these, however, is not well defined. Prevention of joint arthropathy needs to focus on prevention of haemarthroses through prophylaxis, identifying early joint disease through the optimal use of cost effective imaging modalities and the validation of serological markers of joint arthropathy. Screening for effects on bone health and optimal management of pain to improve quality of life are, likewise, important issues.     

高频超声对膝关节半月板急慢性损伤的诊断价值分析

目的分析探讨高频超声对膝关节半月板急慢性损伤的诊断价值。方法选取2017年1月至2018年2月牡丹江医学院第二附属医院收治的50例膝关节半月板急慢性损伤患者(设为研究组)及50例健康体检者(设为对照组)作为研究对象,应用高频超声检测其膝关节滑膜厚度、髌上囊积液深度及滑膜血流状况,并予以对比。结果研究组患者膝关节半月板在基线外侧较为突出且可见点状或条状强回声区,内侧副韧带变形,部分患者伴有不同程度的水肿,滑膜厚度为(6.25±2.20) mm,髌上囊积液深度为(7.35±1.45) mm,滑膜血流为0级者23例、Ⅰ级者12例、Ⅱ级者12例、Ⅲ级者3例;对照组研究对象膝关节半月板回声强度中等且均匀,边缘清晰,滑膜厚度为(1. 10±0.46) mm,髌上囊积液深度为(2. 12±0.43) mm,滑膜血流为0级者38例、Ⅰ级者12例。两组研究对象膝关节滑膜厚度、髌上囊积液深度及滑膜血流状况对比,P均0.01,差异具有统计学意义。结论高频超声对膝关节滑膜厚度、髌上囊积液及滑膜血流均较敏感,在膝关节半月板急慢性损伤的诊断中特异性较高,且操作简便,可作为膝关节半月板急慢性损伤的首选诊断方法予以推广、普及。