Gender differences and protective effects of testosterone in collagen induced arthritis in rats.

To understand the gender differences noticed in autoimmune disorders, particularly rheumatoid arthritis, we used a rat model of collagen induced arthritis (CIA). This study was carried out in two parts. In the first study, severity of inflammation was compared between male and female rats with respect to radiology, histology, activities of lysosomal enzymes, lipid peroxidation, immune response to type II collagen and the level of prostaglandin, a major inflammatory mediator. Since female rats developed severe inflammation, this study was extended to confirm if testosterone at physiological concentration had protective effect against CIA. Hence, studies were carried out on the effect of testosterone application on castrated arthritic rats. Female arthritic rats were also treated with testosterone to find out the effectiveness of the androgen in the presence of female hormones. Results of this study conclusively showed that testosterone possessed significant anti-inflammatory effects at physiological concentration and exerted its action in a gender nonspecific manner.

Optimization of pulsed electromagnetic field therapy for management of arthritis in rats.

Studies were undertaken to find out the effects of low frequency pulsed electromagnetic field (PEMF) in adjuvant induced arthritis (AIA) in rats, a widely used model for screening potential therapies for rheumatoid arthritis (RA). AIA was induced by an intradermal injection of a suspension of heat killed Mycobacterium tuberculosis (500 mug/0.1 ml) into the right hind paw of male Wistar rats. This resulted in swelling, loss of body weight, increase in paw volume as well as the activity of lysosomal enzymes viz., acid phosphatase, cathepsin D, and beta-glucuronidase and significant radiological and histological changes. PEMF therapy for arthritis involved optimization of three significant factors, viz., frequency, intensity, and duration; and the waveform used is sinusoidal. The use of factorial design in lieu of conventional method resulted in the development of an ideal combination of these factors. PEMF was applied using a Fransleau-Braunbeck coil system. A magnetic field of 5 Hz x 4 muT x 90 min was found to be optimal in lowering the paw edema volume and decreasing the activity of lysosomal enzymes. Soft tissue swelling was shown to be reduced as evidenced by radiology. Histological studies confirmed reduction in inflammatory cells infiltration, hyperplasia, and hypertrophy of cells lining synovial membrane. PEMF was also shown to have a membrane stabilizing action by significantly inhibiting the rate of release of beta-glucuronidase from lysosomal rich and sub-cellular fractions. The results indicated that PEMF could be developed as a potential therapy in the treatment of arthritis in humans.