Triptolide, a novel immunosuppressive and anti-inflammatory agent purified from a Chinese herb Tripterygium wilfordii Hook F.

Triptolide is a diterpenoid triepoxide purified from a Chinese herb Tripterygium Wilfordii Hook F (TWHF). TWHF has been used in traditional Chinese medicine for more than two thousand years. However, its potential value was recognized by the western medicine only after investigators observed the effectiveness of TWHF in the treatment of leprosy and rheumatoid arthritis. Triptolide has been identified as the major component responsible for the immunosuppressive and anti-inflammatory effects of TWHF. Triptolide inhibits both Ca(2+)-dependent and Ca(2+)-independent pathways and affects T cell activation through inhibition of interleukin-2 transcription at a site different from the target of cyclosporin A. Triptolide also has inhibitory effects on a variety of proinflammatory cytokines and mediators and on the expression of adhesion molecules by endothelial cells. Triptolide is effective for the treatment of a variety of autoimmune diseases and in prevention of allograft rejection and graft-versus-host disease in both animals and humans. Moreover, triptolide possesses antitumor and male anti-fertility effect. However, the toxicities of triptolide may be associated with renal, cardiac, hematopoietic and reproductive systems. Currently available data suggest that triptolide is a promising immunosuppressive and anti-inflammatory agent and should be explored further in autoimmune diseases and transplantation.

Heel ulcer in leprosy treated with fasciocutaneous island flap from the instep of the sole.

Twenty-four leprous patients with longstanding ulcer of the weight bearing area of the heel underwent reconstruction by use of fasciocutaneous island flap from the instep. One flap was lost because the vascular pedicle was accidentally severed during the dissection. Infection delayed healing in three cases, and one patient developed minor necrosis of the edge of the flap without any adverse consequences. The remaining 18 cases healed without complications. Follow-up of 14 patients 3 to 10 months after the operation showed excellent results in all but the one whose flap was lost. The operation is recommended for difficult reconstructions of the heel.

Adrenal medullary autografts into the basal ganglia of Cebus monkeys: graft viability and fine structure.

Based largely upon studies done in rats, a number of medical centers are now performing autografts of adrenal medullary tissue in consenting patients with Parkinson's disease. However, a systematic experimental evaluation of adrenal medullary autografts in nonhuman primates is necessary. This study provides a detailed analysis of the implant site at the fine structural level 30 days post-transplantation in the Cebus monkey. Five normal and two 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP)-treated Cebus monkeys received adrenal medullary autografts using an open microsurgical approach (n = 3) or via stereotactic placement with a tissue carrier (n = 4). Analysis of preimplant samples of the adrenal medulla confirmed that viable chromaffin cells were implanted into the basal ganglia. However, 30 days later, the implant site resembled a chronic inflammatory focus, with grafted chromaffin cells identified ultrastructurally in only two of the seven transplanted monkeys. The grafted cells showed overt signs of cellular degeneration and were surrounded by phagocytic macrophages. All of the implant sites, regardless of the surgical approach, were filled with macrophages, cells of hematogenous origin, and fibrous astrocytes. The vasculature of the implant site was of the nonfenestrated type, characteristic of the host striatum. Despite the poor survival of implanted chromaffin cells, robust sprouting of tyrosine hydroxylase-like immunoreactive fibers was evident in the striatum adjacent to the implant site (see accompanying manuscript, M.S. Fiandaca, J. H. Kordower, J.T. Hansen, S.-S. Jiao, and D.M. Gash, 1988, Exp. Neurol. 102: 76-91), suggesting that implantation may have precipitated a host response that was beneficial to the transplanted animal. Additional studies that provide a better understanding of the cellular elements residing in the implant site and their potential for trophic influence seem warranted.

Impairment of cell-mediated immune responses by infection with Mycobacterium lepraemurium.

The effect of chronic infection with Mycobacterium lepraemurium upon cell-mediated immune responses was studied in Lewis rats. Rats infected for 40 to 175 days were completely protected from attempted induction of experimental adjuvant disease, and the severity of experimental allergic encephalomyelitis in leprous rats was markedly attenuated. Full manifestations of each autoimmune disease were expressed in littermate control groups. Skin homograft rejection by infected rats was significantly impaired (P less than 0.001) as was the delayed-type hypersensitivity response to sheep erythrocytes (P less than 0.02). It is suggested that chronic infection with M. lepraemurium exerts a nonspecific inhibitory effect on cell-mediated immunity by perturbation of normal lymphocyte recirculation and by induction of immuno-suppressor cell activity.