Seed oil of Joannesia princeps improves cutaneous wound closure in experimental mice.

Joannesia princeps (Cotieira) is a well known medicinal plant in Brazil, however, the therapeutic effects of oil obtained from its seeds have still not been demonstrated. The beneficial effects of J. princeps seed oil on cutaneous wound healing on the back of experimental mice were investigated. An excisional lesion in male Swiss mice (n=20 per group) was topically treated with mineral oil or J. princeps seed oil once a day beginning on the day of lesion until the third day after wounding. Animals were killed and lesions collected after 14 days. Murine skin fibroblast cultures were treated with J. princeps seed oil and fibroblast activity was evaluated. In the in vivo assay, J. princeps seed oil increased wound contraction and migratory tongue length, but reduced neutrophil and macrophage number when compared with the control group. Blood vessel number, collagen deposition, and VEGF levels were increased in treated lesions when compared with control lesions. However, J. princeps seed oil reduced myofibroblast density and carbonyl protein levels when compared with the control group. In the in vitro assay, treatment with J. princeps seed oil increased fibroblast migration and proliferation, but reduced myofibroblastic differentiation in vitro. In conclusion, J. princeps seed oil accelerates wound closure increasing angiogenesis, keratinocyte migration, and fibroblast activity while reducing inflammatory response and oxidative damage.

Cyclosporine A delays wound healing and apoptosis and suppresses activin beta-A expression in rats.

Cyclosporine A is a powerful immunosuppressive agent which is widely used for the prevention of allograft rejection and for the treatment of autoimmune diseases. Clinical and experimental data show that it may also act on connective tissue. We investigated the influence of cyclosporine A on granulation tissue formation and wound healing. Using an in vitro approach, we followed the time course of rat dermal fibroblasts during wound repair. Granulation fibroblasts were compared to dermal fibroblasts flow cytometrically and by mRNA analysis with respect to the expression of procollagen alpha1(I), integrin beta1, interleukin-6, transforming growth factor beta1, keratinocyte growth factor and activin betaA. The most pronounced effect in cyclosporine-treated rats was the strong down-regulation of activin beta expression. In cryo-sections of granulation tissue from the same rats, the distribution and expression intensity of intercellular adhesion molecule and its receptors were investigated by immunohistology. Clearly, a time course was detectable. Tissue from CsA-treated animals showed a delay of three days compared to untreated animals. Apoptosis was also delayed in CsA-treated rats by around three days. Furthermore, we investigated the effect of CsA on the expression of collagen alpha1(I), fibronectin and matrix metalloprotease 1 genes in dermal fibroblasts from untreated donors. No changes in the mRNA steady state levels of these genes were revealed after direct addition of different doses of CsA to fibroblast cultures. Our data suggest that CsA may interfere with the complicated net of interactions between connective tissue and the immune system by down-regulation of the inflammatory phase by modulation of cytokines and a subsequent delay of tissue repair.

Changes in immunostaining of inner ears after antigen challenge into the scala tympani.

To study the mechanisms of immune responses and immune injuries in inner ears, labyrinthitis was induced by inoculation of keyhole limpet hemocyanin (KLH) into the scala tympani of systemically sensitized guinea pigs. Inner ears were then immunostained for KLH, immunoglobulin G (IgG), albumin, connexin26 (Cx26), and sodium-potassium adenosine triphosphate (Na,K-ATPase). Inflammatory cells containing KLH were observed in the scala tympani and in the collecting venule of the spiral modiolar vein (SMV). Spiral ligament, spiral limbus, and blood vessels including the SMV were diffusely positive for IgG and albumin. Immunoreactivity for Cx26 and Na,K-ATPase was decreased compared with the normal ears in the fibrocytes of the spiral ligament. These results suggest that inflammatory cells and blood constituents could extravasate into the cochlea from blood vessels and that fibrocyte damage in the spiral ligament could cause cochlear dysfunction.