[Centennial of the "germ theory and its applications to medicine and surgery", presented by Louis Pasteur in April of 1878].
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Biomedical subjects
Publications and source records attributed to A Delaunay.
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The tension developed in Rat skin by hydrothermal shrinkage is modified with ageing of the animals: the temperature of maximum tension decreases from birth to 1 month, then very slowly increases with age. At higher temperatures than that of maximum tension a relaxation occurs very rapidly in young Rats and in not yet senescent adult skins. These modifications appeared to be related to those of the nature of the intermolecular collagen cross-links with ageing.
In granulation tissue produced in the rat by subcutaneous injection of turpentine oil or polyvynile sponge implantation, the great majority of fibroblasts (myofibroblasts) possess a contractile apparatus which makes them similar to smooth-muscle cells. Chemical analysis shows that these granulation tissues contain a high proportion of Type III collagen, a genetically distinct collagen normally associated with embryonic dermal tissue. Type III collagen may persist up to 9 months after sponge implantation and myofibroblasts are seen in granulation tissue by means of electron microscopy and immunofluorescence. When granulation tissue is resorbed 50 days after turpentine oil injection, myofibroblasts disappear and the dermis contains Type I collagen. The concurrent presence of myofibroblasts and Type III collagen suggests that myofibroblasts, in addition to their contractile activity, synthetize, at least in part, type III collagen.
Collagen is abundantly synthesized in granulation tissues and reaches a concentration higher than in normal neighbouring tissues. Such newly formed collagen is characterized by an abnormally low solubility and an easy degradation by collagenases and collagenolytic cathepsins. The activities of these two types of enzymes are high (especially collagenases) in tissues of acute inflammations when the granuloma is resorbing. These activities are lower in sub-acute inflammation and the collagen content of the persistent granuloma remains high. The collagen synthesized in granulation tissues is cross linked by hydroxylysino-5-keto-norleucine, the stable cross-link of collagen in embryonic skin. It is progressively replaced by the two aldimine cross links of normal adult skin when the granuloma is resorbed (acute inflammations induced in rats; human normal scars). The cross link of embryonic skin, on the contrary, is permanently present in collagen of tissues of subacute, chronic inflammations (sponge implants in rats, human hypertrophic scars and keloids. Studies of the structure of alpha-chains revealed that type III collagen (embryonic collagen) is present in granulation tissues.
Collagen similar to the collagen found in embryonic skin (same intermolecular cross-links and same structure of the polypeptide chains) is synthesized in young human scars. Later on, in normal scars, this collagen is replaced by the collagen of adult skin progressively. In contrast, in hypertrophic scars, a high proportion of collagen of "embryonic" type is present permanently. In granulation tissues of chronic inflammation, experimentally developed in rats, similar "embryonic" collagen has been found ; these granuloma are proposed as a model in laboratory animals of human hypertrophic scars.
The collagen produced in response to an injury of human skin is initially stabilized by a cross-link derived from hydroxyallysine, and characteristic of embryonic skin. In normal healing there is a change over with time to the cross-link derived from allysine, which is typical of young skin collagen. In contrast, hypertrophic scars fail to follow the time-related changes of normal skin, but retain the characteristics of embryonic collagen, indicating a continued rapid turnover of the collagen. This is further supported by the high proportion of the embryonic Type III collagen present in hypertrophic scars.
Specific collagenases are activated rapidly in inflamed tissues. This activity reaches a higher level in acute inflammation than in chronic inflammation. It appears to be related to an increased metabolic activity of the local fibroblasts.
Incubated in vitro at 37 degrees C, granulation tissues release glycosaminoglycans into the incubation medium. Such release is inhibited if pepstatine is present in the medium. From this result, it can be inferred that the protien moiety of the proteioglycans is degraded by cathepsin D. Therefore a role of this enzyme in granulation tissues appears, especially in the late reparative phase.
The collagen, abundantly accumulated in the liver of carbon tetrachloride treated rats, is highly resistant to dissociative agents, indicating a stron cross-linkage. However, even after a very long treatment, such collagen can be resorbed.
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