hydroxylysine and Fibrosis

Changes in the process of cross-linking of collagen molecules are associated with defects in the biomechanical stability of the extracellular matrix. Fibrosis of skin is characterized by an increase in pyridinolines, which are hydroxylysine aldehyde derived cross-links usually absent in healthy skin. In this study, we analyzed cross-links in lipodermatosclerosis and localized scleroderma to address the question whether all the mature cross-links currently characterized are increased in fibrosis in addition to the increase in pyridinolines. As psoralen plus ultraviolet A treatment leads to clinical improvement of fibrotic plaques in localized scleroderma we analyzed the cross-link content in lesional skin after bath psoralen plus ultraviolet A therapy. In skin from patients with localized scleroderma an increase in the total number of mature cross-links was found to be due to an increase in both pyridinolines and dehydro-histidinohydroxymerodesmosine. The concentration of histidinohydroxylysinonorleucine was unchanged. By contrast, the total number of mature cross-links was decreased in lipodermatosclerosis. This decrease was caused by a decrease of lysine aldehyde derived cross-links (dehydro-histidinohydroxymerodesmosine and histidinohydroxylysinonorleucine), whereas the concentration of pyridinolines increased. A decrease in the content of pyridinolines after bath psoralen plus ultraviolet A treatment was found in six out of nine patients with localized scleroderma, which might reflect a remodeling of the extracellular matrix. Our data provide evidence that sclerosis of skin is associated with either an increase in the number of cross-links per molecule of collagen or a change in the molecular nature of the cross-links formed.

Topics: Amino Acids; Collagen; Cross-Linking Reagents; Desmosine; Fibrosis; Humans; Hydroxylation; Hydroxylysine; PUVA Therapy; Pyridones; Scleroderma, Localized; Ultraviolet Rays

Gross morphology of healthy and degenerated intervertebral discs (IVDs) is largely similar in horses as in dogs and humans. For further comparison, the biochemical composition and the histological and biochemical changes with age and degeneration were analyzed in 41 warmblood horses. From 33 horses, 139 discs and 2 fetal vertebral columns were evaluated and scored histologically. From 13 horses, 73 IVDs were assessed for hydration, DNA, glycosaminoglycans, total collagen, hydroxyl-lysyl-pyridinoline, hydroxylysine, and advanced glycation end-product (AGE) content. From 7 horses, 20 discs were assessed for aggrecan, fibronectin, and collagen type 1 and 2 content. Histologically, tearing of the nucleus pulposus (NP) and cervical annulus fibrosus (AF), and total histological score (tearing and vascular proliferation of the AF, and chondroid metaplasia, chondrocyte-like cell proliferation, presence of notochordal cells, matrix staining, and tearing of the NP) correlated with gross degeneration. Notochordal cells were not seen in IVDs of horses. Age and gross degeneration were positively correlated with AGEs and a fibrotic phenotype, explaining gross degenerative changes. In contrast to dogs and humans, there was no consistent difference in glycosaminoglycan content and hydration between AF and NP, nor decrease of these variables with age or degeneration. Hydroxylysine decrease and collagen 1 and AGEs increase were most prominent in the NP, suggesting degeneration started in the AP. In caudal cervical NPs, AGE deposition was significantly increased in grossly normal IVDs and total collagen significantly increased with age, suggesting increased biomechanical stress and likelihood for spinal disease in this part of the vertebral column.

Topics: Animals; Collagen; Dog Diseases; Dogs; Fibrosis; Horse Diseases; Horses; Hydroxylysine; Intervertebral Disc; Intervertebral Disc Degeneration

Laser therapy is today considered the treatment of choice for vascular skin lesions, which commonly are located on the face and, therefore, frequently are exposed to sunlight. The purpose of this study was to examine whether preoperative and postoperative ultraviolet irradiation influences the development of laser-induced side effects. We laser-treated hairless mice with a copper vapor laser; three different intensities were used at a constant pulse duration. Simulated solar ultraviolet radiation was administered either before the laser treatment (3 consecutive days, daily doses of 2.48 J/cm2) or after the laser treatment (four times weekly in 4 weeks, daily doses of 1.66 J/cm2). Laser-induced wounds, scars, and hyperpigmentation were evaluated by macroscopic, histologic, and biochemical examinations. Preoperative ultraviolet exposure enlarged the laser-induced wounds and the areas with texture change at some of the laser intensities used. However, the most pronounced effect was seen for postoperative ultraviolet-irradiated mice. These mice developed, at some of the laser intensities, a higher incidence of bulging infiltration as well as higher degrees of fibrosis and hyperpigmentation, thus developing a poor cosmetic appearance. Furthermore, ultraviolet irradiation after laser treatment resulted in slowly healing wounds of reduced size, indicating deep, constricted skin damage. We conclude that ultraviolet exposure before and after copper vapor laser treatment increases the risk of inducing side effects from dermatological laser treatment.

Topics: Animals; Cicatrix; Contracture; Copper; Dermatologic Surgical Procedures; Esthetics; Facial Dermatoses; Female; Fibrosis; Hydroxylysine; Hydroxyproline; Hyperpigmentation; Incidence; Laser Coagulation; Mice; Mice, Hairless; Mice, Inbred C3H; Mice, Inbred Strains; Proline; Radiation Dosage; Risk Factors; Skin; Skin Diseases; Skin Diseases, Vascular; Skin Pigmentation; Sunlight; Ultraviolet Rays; Wound Healing

Scarring is a well-known side effect to cutaneous laser treatment. Therefore we investigated if wounds and scarring could be decreased by pharmacological interference in the acute inflammatory reaction following laser therapy. A copper vapor laser operating at 578 nm was used at three different intensities and doses. The antiinflammatory drugs methylprednisolone (1 mg/kg/24 h) and indomethacin (2 mg/kg/24 h) were administered through the drinking water. The laser induced wounds were evaluated daily and histologic and biochemical analyses were used to estimate scarring. The administration of antiinflammatory drugs resulted at some laser intensities in increased scores of maximum wound area, healing time, cumulated wound area, fibrosis, hydroxyproline, and hydroxylysine, being mostly pronounced for indomethacin at 0.8 W/spot. The maximum wound area and the wound healing time could be used as a predictor of scarring. A dose response was shown between the laser intensities and the mentioned parameters. We recommend carefulness in the laser treatment of patients receiving indomethacin and disrecommend use of the drug in the prophylaxis against laser induced scarring.

Topics: Administration, Oral; Animals; Burns; Cicatrix; Dose-Response Relationship, Radiation; Female; Fibrosis; Hydroxylysine; Hydroxyproline; Indomethacin; Laser Therapy; Methylprednisolone; Mice; Mice, Inbred C3H; Mice, Nude; Proline; Skin; Wound Healing

Scarring is a well-known side-effect of cutaneous laser treatment and exposure to solar ultraviolet radiation is suspected to increase scar formation. We investigated how wounds and scarring were modified by interfering in the laser-induced inflammation using ultraviolet radiation and para-aminobenzoic acid. A copper vapour laser operating at 578 nm was used at three different intensities and doses. The ultraviolet radiation was administered three times weekly prior to and four times weekly after the laser treatment. The daily dose was 21.5 kJ/m2 equivalent to 3.5 Basic-MED. The laser-induced wounds were evaluated daily and histological and biochemical analyses were used to estimate scarring. Ultraviolet irradiation resulted at some of the used laser intensities in decreased scores of maximum wound area, wound healing time, cumulated wound area, and a decreased skin content of hydroxyproline, whereas the degree of the chronic fibrosis tended to increase. Application of para-aminobenzoic acid before the solar ultraviolet irradiation did not change the acute wound scores but reduced, although not significantly, the degree of fibrosis.

Topics: 4-Aminobenzoic Acid; Animals; Cicatrix; Female; Fibrosis; Hydroxylysine; Hydroxyproline; Laser Therapy; Lasers; Mice; Mice, Hairless; Skin; Ultraviolet Rays; Wound Healing