Symposium on equine bone and joint diseases. Osteolysis in pathological material.
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IL-6 is a multifunctional cytokine produced by lymphoid and nonlymphoid cells; it regulates immune responses, acute-phase reactions, and inflammation. IL-6 signaling is mediated exclusively by the common signal-transducing component gp130, which is also essential for signal transduction of other cytokines of the leukemia inhibitory factor (LIF)/IL-6 family. M Ernst and colleagues generated and studied knock-in mice (gp130DeltaSTAT/DeltaSTAT), in which all STAT-binding sites (sites binding signal transducers and activators of transcription) were deleted from their gene encoding gp130 but binding sites for both Janus kinases (JAKs) and for the protein tyrosine phosphatase-2 (SHP-2) were preserved. They found that this mutant mouse displayed a blastocyst implantation defect, gastrointestinal ulceration, and, interestingly, severe joint disease with representative features of rheumatoid arthritis. Synovial cells from this mouse exhibited mitogenic hyper-responsiveness to cytokines of the LIF/IL-6 family, a phenomenon that was caused by sustained gp130-mediated SHP-2/Ras/Erk activation due to a defect in the induction of SOCS-1 (suppressor of cytokine signaling-1; also known as SSI or JAB). This suppressor, induced by STAT signaling, regulates cytokine signaling. It is, therefore, conceivable that the disturbance of the balanced activation between the STAT and SHP-2/Ras/Erk signal pathways causes the joint disease in the gp130DeltaSTAT/DeltaSTAT mouse. These findings may be beneficial in the elucidation of the cause and the treatment of rheumatoid arthritis in humans.
Ventrodorsal (VD) radiographs of cadaveric pelves of large and giant breeds (n = 40) and of the corresponding bone specimens were made. Gross changes seen in the specimens were marked with metal wire or radiopaque paint to relate radiographic changes to the postmortem appearance of degenerative sacroiliac (SI) joint lesions. Two positioning techniques were used, resulting in two radiographs for each specimen. The techniques used were: (1) pulling the pelvic limbs caudally, with gentle traction producing a view of the sacrum in almost parallel alignment between the sacrum and the X-ray film (we have termed this a "central SI view") and (2) pulling the pelvic limbs caudally with greater traction than above, resulting in maximal inclination of the sacrum with respect to the X-ray film (we have termed this an "angled SI view"). Lesions of the supportive soft connective tissue could be imaged on the central and angled SI views, whereas angled SI views allowed better identification of lesions of the synovial SI joint. The insights gained in the above study were then used in a retrospective examination of 145 routine ventrodorsal radiographs of the pelvis (i.e., 290 sacroiliac joints) to determine the incidence of degenerative changes of the SI joint in large dogs. The lesions most commonly observed were calcification of the supportive soft connective tissue (n = 184/290), whereas lesions of the synovial SI joint were less frequent (n = 86/290). The degree of central or angled projection obtained in standard ventrodorsal radiographs was noted to be significantly (P < 0.05) associated with age, body conformation, anesthetic status, and the presence of spondylosis deformans at the lumbosacral junction. In contrast, SI joint disease and the gender of the animal did not affect the SI view achieved in VD radiographs.
We evaluated the monoclonal antibody MAb, BW 250/183, which is easy to label with Tc-99m, with respect to its clinical application for the detection of inflammatory processes in bone and joint diseases. This monoclonal antibody is a murine immunoglobulin (IgG1 isotype), directed against NCA 95 (nonspecific cross-reacting antigen), which is also present on the surface of neutrophil granulocytes. We investigated patients with acute (n = 9) and chronic (n = 3) osteomyelitis, with coxitis (n = 3) and coxarthrosis (n = 2), with septic hip prosthesis (n = 8) and loosening hip prosthesis (n = 14), with low back pain (n = 4), with spondylitis (n = 5) and with postoperative spondylodiscitis (n = 9). With reference to the total number of patients examined in this study we found 29 true positive results, 22 true negative results, 4 false negative results and 2 false positive results. This gives a sensitivity of 88% and a specificity of 92%. The lesions were already visualized within 4 to 6 hours, but 24 hour pictures are desirable. SPECT pictures are mandatory in patients with diseases of the hip or of the spine because sensitivity is considerably improved thereby.
The principles of physical rehabilitation therapy can be applied to the horse to provide a reduction in discomfort and dysfunction associated with the various forms of joint disease. Physical agents,such as ice, heat, electricity, sound, light, magnetic fields, compression, and movement, can be used by the rehabilitation therapist to attempt to control pain, reduce swelling, and restore optimal movement and function in the affected joint. The equine therapist's attention is focused not only on the affected joint but on the body as a whole to manage secondary or compensatory problems.
A 17-year-old girl with temporomandibular joint disease who had been treated with the usual types of treatment for 8 1/2 years by multiple clinicians was treated using hypnosis as an adjunct. The treatment, which is described in detail, was successful for 6 months until the patient transferred to an urban college where additional academic and personal pressures caused her bruxism symptoms to reappear. Probable causes of the relapse are discussed.
Information on the structure and metabolism of a number of matrix constituents of cartilage has accumulated rapidly during the last decades. Altered dynamics of cartilage matrix in joint diseases results in increased release of macromolecules, which are now explored as potential markers of damage and severity. This article highlights some recent progress in this field with emphasis on cartilage derived proteoglycan. Disease and therapy related changes may be studied and prognostic information may be obtained by analysis of joint fluid. Future applications of this approach are promising.
Cathepsins play important roles in the development of joint and bone diseases such as osteoporosis, rheumatoid arthritis (RA) and osteoarthritis (OA). Cathepsin inhibitors are presently in development and clinical testing for use as novel disease-modifying drugs for the improved treatment of osteoporosis. They may also be applicable for the treatment of joint diseases. However, some barriers still hamper their clinical applications in these indications. Based on pathophysiological features of RA and OA, the authors discuss six potential drug delivery strategies for the effective delivery of cathepsin inhibitors or other antiarthritic drugs to the arthritic joint tissue. Successful application of these strategies may significantly contribute to a more effective and safe treatment of RA and OA.
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