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Involvement of the kinin-forming system in the physiopathology of rheumatoid inflammation

Sharma JN

Agents Actions Suppl., 1992;38 ( Pt 3):343-61.
PMID: 1334358

Kinins are potent mediators of rheumatoid inflammation. The components of the kinin-forming system are hyperactive in RA. Excessive release of kinins in the synovial fluid can produce oedema, pain and loss of functions due to activation of B1 and B2 receptors. These receptors could be stimulated via injury, trauma, coagulation pathways (Hageman factor and thrombin) and immune complexes. The activated B1 and B2 receptors might cause release of other powerful non-cytokines and cytokines mediators of inflammation, for example, PGE2, PGI2, LTs, histamine, PAF, IL-1 and TNF derived mainly from polymorphonuclear leukocytes, macrophages, endothelial cells and synovial tissue. These mediators are capable of inducing bone and cartilage damage, hypertrophic synovitis, vessels proliferation, inflammatory cells migration, and possibly angiogenesis in pannus formation. These pathological changes, however, are not yet defined in human model of chronic inflammation (RA). Hence, the role of kinin and its interacting inflammatory mediators would soon start to clarify the detailed questions they revealed in clinical and experimental models of chronic inflammatory joint diseases. Several B1 and B2 receptor antagonists are being synthesized in an attempt to study the molecular functions of kinins in inflammatory processes (RA, periodontitis and osteomyelitis), and they represent and important area for continued research in rheumatology. Future development of specific, potent and stable B1 and B2 receptor antagonists or combined B1 and B2 antagonists with y-IFN might serve as pharmacological basis of more effective rationally-based therapies for RA. This may lead to significant advances in our knowledge of the mechanisms and therapeutics of rheumatic diseases.

Matched MeSH terms: Joints/physiopathology*
The effect of leg length inequality on joint contact forces of lower limbs during walking

Fazreena Othman N, Salleh Basaruddin K, Hanafi Mat Som M, Shukry Abdul Majid M, Razak Sulaiman A

Acta Bioeng Biomech, 2019;21(1):55-62.
PMID: 31197285

PURPOSE: The aim of this study was to examine the joint contact forces (JCF) between each limb as the LLD magnitude increases during walking activity.
METHODS: Eighteen male healthy subjects volunteered to participate in the experiment. Walking gait analysis was conducted with eight different levels of insole to simulate the LLD, starting from 0 cm until 4.0 cm with 0.5 cm increment. Qualisys Track Manager System and C-motion Visual 3D biomechanical tools were used to analyse the results. Four joints (ankle, knee, hip, and pelvis) of lower limb of two legs were investigated. The increment of insoles was placed on the right leg to represent the long leg.
RESULTS: The results suggest that the mean contact forces for all joints in the short leg were increased as the increment level increased. On the contrary, the mean contact forces in the long leg decreased when the LLD level increased. Among these four joints, JCF in hip shows a positive increment based on the ASI value. Means that hip shows the most affected joint as the LLD level increase.
CONCLUSIONS: The result obtained in this study might help clinicians treat patients with a structural LLD for treatment plan including surgical intervention.

Matched MeSH terms: Joints/physiopathology*
Biomechanical evaluation of two commonly used external fixators in the treatment of open subtalar dislocation--a finite element analysis

Ramlee MH, Kadir MR, Murali MR, Kamarul T

Med Eng Phys, 2014 Oct;36(10):1358-66.
PMID: 25092623 DOI: 10.1016/j.medengphy.2014.07.001

Subtalar dislocation is a rare injury caused by high-energy trauma. Current treatment strategies include leg casts, internal fixation and external fixation. Among these, external fixators are the most commonly used as this method is believed to provide better stabilization. However, the biomechanical stability provided by these fixators has not been demonstrated. This biomechanical study compares two commonly used external fixators, i.e. Mitkovic and Delta. CT imaging data were used to reconstruct three-dimensional models of the tibia, fibula, talus, calcaneus, navicular, cuboid, three cuneiforms and five metatarsal bones. The 3D models of the bones and cartilages were then converted into four-noded linear tetrahedral elements, whilst the ligaments were modelled with linear spring elements. Bones and cartilage were idealized as homogeneous, isotropic and linear. To simulate loading during walking, axial loading (70 N during the swing and 350 N during the stance phase) was applied at the end of diaphyseal tibia. The results demonstrate that the Mitkovic fixator produced greater displacement (peak 3.0mm and 15.6mm) compared to the Delta fixator (peak 0.8mm and 3.9 mm), in both the swing and stance phase, respectively. This study demonstrates that the Delta external fixator provides superior stability over the Mitkovic fixator. The Delta fixator may be more effective in treating subtalar dislocation.

Matched MeSH terms: Foot Joints/physiopathology
Fulltext Domains of quality of life affecting elderly patients with hand osteoarthritis: a qualitative study in the Asian perspective

Thumboo J, Wu L, Leung YY

Int J Rheum Dis, 2017 Sep;20(9):1105-1119.
PMID: 26990791 DOI: 10.1111/1756-185X.12843

OBJECTIVES: Hand osteoarthritis (HOA) is common but little is known about how HOA has impact on disability and quality of life (QoL).We aim to identify important domains of concern among participants suffering from symptomatic HOA in Singapore, representing an Asian socio-cultural context.
METHODS: A qualitative study using a focus group technique was performed. We ran focus groups stratified by gender, ethnicity and language. Two independent, trained analysts identified relevant categories and assigned codes to text segments through open coding, with discrepancies resolved through consensus. The final lists of domains and subthemes descriptive of QoL were then compared to the following commonly used HOA specific instruments: Functional Index for Hand Osteoarthritis (FIHOA), Score for Assessment and quantification of Chronic Rheumatic Affections of the Hand (SACRAH), Australian/Canadian Hand Osteoarthritis Index (AUSCAN); and Health Assessment Questionnaire (HAQ).
RESULTS: Twenty-six patients (23 women, three men; 24 Chinese and two Malay; mean ± SD age 62.9 ± 7.5 years) with symptomatic HOA according to the American College of Rheumatology Classification Criteria participated in seven focus groups. Two and five focus groups were conducted in Chinese and English, respectively. The qualitative analysis revealed pain, stiffness and functional disability as the main domains. However, psychological consequences, aesthetic concerns, participation in leisure activities, participation in family roles were important concepts from the focus groups which were not covered by existing instruments. Impact on work productivity by HOA and the unmet health care need is revealed.
CONCLUSION: The domains of concepts important to people with HOA in an Asian socio-cultural context are not fully represented in the most commonly used instruments. Further studies on the selection of main domains relevant to HOA patients are necessary.
Study site: Rheumatology outpatient clinic, Singapore General Hospital

Matched MeSH terms: Hand Joints/physiopathology*