- Posts: 213
- Karma: 4
- Thank you received: 0
Please Log in to join the conversation.
Please Log in to join the conversation.
The subject invention additionally provides a method of promoting cartilage repair in a patient which comprises administering an oxandrolone to the patient.
EXAMPLE 1: The effect of oxandrolone on inflammation
The rat model of carrageenan-induced paw edema is used to assay the anti-inflammatory activity of oxandrolone. In this model, rats are given a sub-plantar injection of carrageenan into the left hind paw. The paw volume is measured by a Hg-displacement volumeter before and at hourly intervals after paw injection. Rats are divided into three groups. One group receives a subcutaneous injection of oxandrolone long before carrageenan administration. A second group receives a subcutaneous injection of oxandrolone closer to carrageenan administration. The other group does not receive any pretreatment and serves as a control.
The swelling response is reduced indicating efficacy of oxandrolone as an anti-inflammatory agent.
EXAMPLE 2 : The effect of oxandrolone on Synovial Inflammation
As a model for synovial inflammation and the ability of oxandrolone to inhibit such inflammation, the knee-joint (synovial) inflammation model in rats is utilized. (Ginsburg et al . , in "Bayer-Symposium VI: Experimental Models of Chronic Inflammatory Diseases", 256-299, 1977, Springer-Verlag) .
In this model, inflammation is induced by intraarticular injection of bacterial lipopolysaccharide endotoxin (LPS) . The degree of inflammation is reflected by the swelling of the synovial tissue and is measured as the increase in weight postadministration. The LPS toxin and oxandrolone are co-administered.
The LPS-induced synovial inflammation is inhibited which indicates efficacy of oxandrolone as an inhibitor of synovial inflammation.
EXAMPLE 3: The effect of Oxandrolone on Adjuvant-Induced Arthritis
The induction of joint inflammation in rats by administration of Freund's adjuvant is considered to be the model of choice for experimental rheumatoid arthritis (Newbould (1963), Brit. J. Pharmacol. 21: 127). An injection of the adjuvant (Freund's adjuvant with killed Mycobacterium Tuberculosis) into the foot pad results in an initial swelling of the paw, reaching a plateau after 3 days, followed after 14 days by a second increase in,paw and joint swelling, which persists for another 7-10 days. The second phase is regarded as the phase of immunologically- induced chronic arthritis. To examine the efficacy of oxandrolone as an anti-arthritic drug, oxandrolone is given subcutaneously (in doses expressed as mg per kg body weight) to adjuvant-treated rats during 14-21 days after adjuvant administration. Oxandrolone is given daily or on alternating days. As a negative control, saline is given subcutaneously to a second group of adjuvant-treated rats.
Joint inflammation is reduced which indicates efficacy of oxandrolone as an inhibitor of arthritis.
Androgens have been shown to inhibit IL-6 production by stromal and osteoblastic cells as well as stimulation of osteoclastogenesis by marrow osteoclast precursors [125, 126].
CONCLUSION: This followup study showed that individuals were more likely to be diagnosed as having RKOA if they had a higher BMI and increased circulating levels of IL-6. These results should stimulate more work on IL-6 as a potential therapeutic target.
DISCUSSION
This study demonstrates the increased presence of IL-6 in the synovial fluid of patients with symptomatic cartilage lesions and OA donors when compared to healthy donors. Furthermore, we demonstrated for the first time that chondrocytes produce high concentrations of IL-6 during regeneration, especially osteoarthritic chondrocytes. However, IL-6 does not seem to play a direct role in cartilage matrix turnover. Furthermore, only in OA chondrocytes, IL-6 does seem to play a role in proliferation, although the effect was
different in explants in the presence of synovial fluid compared to 3D differentiation by expanded chondrocytes.
SIGNIFICANCE
Soluble mediators, including IL-6, in the synovial fluid of knees with symptomatic cartilage defects are thought to cause progression to osteoarthritis and also hamper cartilage regeneration after cartilage surgeries such as autologous chondrocyte implantation. Identifying and targeting those soluble mediators will increase the success of cartilage
repair surgery and prevent the progression to early osteoarthritis.
Please Log in to join the conversation.
Please Log in to join the conversation.