[[Cyclosporin forever?].

The author presents a summarized review concerning the use of cyclosporine in the control of graft rejection. He insists on the need to reduce as far as possible the cyclosporine dosage applied. This can be achieved in association with other drugs, such as azathioprine and/or steroids.

The mode of action of immunosuppressive drugs.

The immunosuppression first introduced in the 1950s acted indiscriminately, blocking or damaging all the cells that happened to be in mytosis. The toxic side effects were usually so severe that the overall results were not considered satisfactory. The major drawback to the commonly used combination of steroids and cytotoxic drugs is the high risk of overwhelming infections.

[Lack of transformation of the collagen substratum in collagen lattice cultures].

Human dermal fibroblasts were seeded into collagen lattices (tridimensional meshwork) of two preparations: (1) acid-extracted, (2) pepsin-digested-calf skin collagens. Lattices prepared with pepsin-digested collagen retracted faster during the first 2 days, then the two preparations gave the same contraction pattern. Lattices of both preparations were contracted for up to 23 days and their collagens submitted to CNBr treatment.

Fibronectin dependence of the contraction of collagen lattices by human skin fibroblasts.

The role of fibronectin in the contraction of collagen lattices by human skin fibroblasts has been investigated. Incubation of lattice cultures in Dulbecco's modified Eagle's medium supplemented with increasing concentrations of non-dialysed or dialysed fetal calf serum demonstrated that the rate of contraction was dependent on non-dialysable serum components. The suppression of contraction observed when fibronectin was eliminated from serum, either by affinity chromatography on gelatin-agarose columns or by precipitation with anti-fibronectin antibodies, showed that fibronectin is critical for the contraction.

Effects of isaxonine phosphate and analogs on fibroblast metabolism in culture.

Human skin fibroblasts in confluent cultures were incubated for 24 h in the presence of isaxonine phosphate (Nerfactor) and several related factors. The incorporation of 14C-proline into secreted proteins and the release of collagen into the medium were inhibited. When the cells were incubated for an additional period of 24 h after thorough washing, protein and collagen syntheses were found to be identical to those of controls, demonstrating that the inhibition of protein synthesis was independent of any toxic effect.

[Effect of oxygen free radicals on collagen in inflammation].

Oxygen derived free radicals are able to degrade collagen fibrils and to participate with the collagenases to collagen degradation in the inflammatory phenomena. This effect was experimentally demonstrated in vitro by the use of chemical or physical systems of oxygen free radicals production. In addition certain free radicals increase the cross-linking of collagen.

A comparison of the effectiveness of cyclosporine A, D, and G in the treatment of experimental autoimmune uveitis in rats.

Cyclosporine A (CsA), one compound in the family of cyclosporines, has effectively modulated the course of S-antigen induced experimental autoimmune uveitis (EAU). Cyclosporines G (CsG) and D (CsD), related to CsA in structure, were evaluated in their ability to prevent or modulate EAU in Lewis rats. 10 mg/kg/day IM of CsA effectively prevented the expression of EAU when therapy began on the day of immunization, while the same dosage of CsG prevented EAU in 81% of animals, and CsD only in 33%.

[Increased retraction of collagen lattices by fibroblasts from patients with scleroderma].

Skin fibroblasts from eight scleroderma patients were seeded in collagen lattices, and their capacity of retraction was compared to that of fibroblasts from normal volunteers. In all cases, pathological fibroblasts retracted collagen lattices earlier and more intensively than controls. This in vitro feature may be related to the cutaneous retraction which characterizes scleroderma lesions in vivo.

A study of collagen metabolism in cell cultures by fluorometric determination of proline and hydroxyproline.

A technique of derivatization of proline (Pro) and 4-hydroxyproline (Hyp) by 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole permitted the measurement of Pro and Hyp radioactivities, concentrations, and specific activities in the main fractions separated from cultures of fibroblast cells (extracellular collagen and non-collagen proteins, intracellular free Pro and Hyp, Pro- and Hyp-containing peptides, procollagen, and non-collagen proteins). The evaluation of collagen in the medium was obtained from as few as 10(4) cells. The method might advantageously replace [14C] Pro or [3H] Pro incorporation studies.

Inhibition of collagen production in scleroderma fibroblast cultures by a connective tissue glycoprotein extracted from normal dermis.

It was shown in a previous paper that a connective tissue glycoprotein (CTGP) extracted from normal rabbit dermis was able to inhibit total protein and collagen syntheses by normal dermis fibroblast cultures. In the present study, the effects of CTGP on scleroderma fibroblasts were investigated. [14C]Proline incorporation into total proteins of the supernatant was not significantly different from that found in controls.

Modifications of collagens in the course of inflammatory tracheal stenoses.

A comparison was made between the biochemical and histological properties of collagens contained in samples of normal tracheas obtained at autopsy or of stenosed tracheas obtained during surgery. The amounts of total collagen solubilized by pepsin was increased seven times in the pathological samples, and the proportion of cartilage type II collagen decreased by about one half, being replaced by type I collagen, whose ratio was increased five times. Microscopic studies confirmed that cartilage underwent a degenerative process and was progressively infiltrated by fibrils of interstitial collagen.