chondroitin-sulfates and Skin-Diseases

The loss of skin has been one of the oldest, yet most frequent and costly problems in our health care system. To restore functional and esthetic integrity in patients with unstable or hypertrophic scars, in burn patients and after skin loss for hereditary, traumatic or oncological reasons, an armamentarium of reconstructive surgical procedures including autogenous, allogenous and xenogenous tissue transfer as well as implantation of alloplastic materials has been favored. For several decades there has been increasing interest focused on 'tissue engineering' of dermal, epidermal and full thickness skin substitutes by both biological and synthetic matrices. At our institution (Hannover Medical School), a collagen/glycosaminoglycan dermal regeneration matrix has been used for immediate dermal coverage after escharectomy in burn injuries as well as for dermal replacement in chronically unstable scars. This article gives an overview on the current state of the art in bioartificial skin as well as our personal experience with the collagen/glycosaminoglycan matrix for dermal replacement in different clinical situations.

Topics: Adolescent; Adult; Biocompatible Materials; Burns; Chondroitin Sulfates; Cicatrix; Collagen; Dermis; Epidermis; Extracellular Matrix; Female; Follow-Up Studies; Glycosaminoglycans; Humans; Middle Aged; Silicones; Skin Diseases; Skin Transplantation; Skin, Artificial

There are three distinct syndromes of heparin-induced thrombocytopenia: an acute reversible from seen immediately after intravenous bolus injection, a delayed-onset antibody-mediated form seen several days after the initiation of therapy, and an intermediate type characterized by mild thrombocytopenia developing just a few days after starting therapy. Delayed-onset heparin-induced thrombocytopenia, clinically the most important form, results from the formation of heparin-dependent antibodies that are directed against the platelet membrane. In the presence of heparin, these antibodies may induce in vitro or in vivo platelet aggregation. Consequently, the course may be complicated by arterial thromboses. Treatment of this syndrome includes the prompt cessation of heparin. Since continued or future anticoagulation is usually necessary, alternative means of anticoagulation have been explored. Oral anticoagulation is often started but requires several days to take effect. Other options include low-molecular-weight heparins, antiplatelet agents, prostacyclin analogues, and low-molecular-weight dextran. In vitro laboratory tests may be helpful in guiding alternative therapy in some, but not all cases. Unfortunately, none of these agents have proved to be uniformly effective and additional agents and clinical investigation are needed before a definitive option becomes available.

Topics: Aspirin; Cardiopulmonary Bypass; Chondroitin Sulfates; Dermatan Sulfate; Epoprostenol; Fibrinolytic Agents; Glycosaminoglycans; Heparin; Heparinoids; Heparitin Sulfate; Humans; Iloprost; Necrosis; Platelet Aggregation Inhibitors; Skin; Skin Diseases; Thrombocytopenia; Thrombosis

Xeroderma pigmentosum is a rare and severe photodermatitis without cure. Skin cancers are inevitable and give rise to iterative skin resections often mutilating especially in the face. We report the case of two sisters suffering from severe forms of xeroderma pigmentosum. Given the rapid emergence of multicancerous lesions, we opted for a radical approach entailing successively all aesthetic sub-units of the face. The reconstruction uses an original method used initially in the great burned: the artificial dermis. This simple method, providing a quality sub-soil, has helped us in these two complex cases to ensure coverage of a large defect providing a tissue recovery of excellent trophic and aesthetics quality. Thanks to this treatment strategy, we were able to significantly delay the development of this disease. With a retreat of 35 months, the quality of reconstruction by artificial dermis is considered to be satisfactory for its elasticity and its trophicity.

Topics: Child; Chondroitin Sulfates; Collagen; Face; Female; Follow-Up Studies; Humans; Plastic Surgery Procedures; Siblings; Skin Diseases; Treatment Outcome; Xeroderma Pigmentosum

Keloid is a fibrotic disease characterized by abnormal accumulation of extracellular matrix in the dermis. The keloid matrix contains excess collagen and glycosaminoglycans (GAGs), but lacks elastic fiber. However, the roles of these matrix components in the pathogenesis of keloid are largely unknown. Here, we show that elastin and DANCE (also known as fibulin-5), a protein required for elastic fiber formation, are not deposited in the extracellular matrix of keloids, due to excess accumulation of chondoitin sulfate (CS), although the expression of elastin and DANCE is not affected. Amount of CS accumulated in the keloid legion was 6.9-fold higher than in normal skin. Fibrillin-1, a scaffold protein for elastic fiber assembly, was abnormally distributed in the keloid matrix. Addition of purified CS to keloid fibroblast culture resulted in abnormal deposition of fibrillin-1, concomitant with significantly decreased accumulation of elastin and DANCE in the extracellular matrix. We propose that CS plays a crucial role in the development of keloid lesions through inhibition of elastic fiber assembly.

Topics: Adolescent; Adult; Aged; Child; Chondroitin Sulfates; Elastic Tissue; Female; Humans; Keloid; Male; Middle Aged; Skin Diseases; Young Adult

Topics: Administration, Cutaneous; Biopsy; Chondroitin Sulfates; Collagen; Granuloma, Pyogenic; Humans; Male; Melanoma; Middle Aged; Postoperative Care; Silver Nitrate; Skin Care; Skin Diseases; Skin Neoplasms; Skin Transplantation; Wound Healing

Topics: Anticoagulants; Blood Coagulation Factors; Chondroitin Sulfates; Dermatan Sulfate; Dose-Response Relationship, Drug; Drug Combinations; Drug Hypersensitivity; Drug Monitoring; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Humans; Injections, Subcutaneous; Risk Factors; Skin Diseases; Thromboembolism

A 52-year-old man had been in terminal renal failure for 6 years. On haemodialysis under heparin without complications, acral skin necroses occurred. Even with low-molecular heparin anticoagulation further lesions developed. Within 12 weeks of haemodialysis being performed without heparin the necroses healed, but they recurred when heparin was again added for dialysis. On admission the patient was in poor general condition, with a weight of 55 kg (height 175 cm). LABORATORY INVESTIGATIONS: The heparin-induced platelet aggregation (HIPA) test was positive in the absence of thrombocytopenia. Na-heparin reacted positively in three out of four tests, but Danaparoid did not react.. The skin necroses once again healed after the heparinoid Danaparoid, which had not reacted in the HIPA test, had been substituted for heparin.. This case illustrates that skin necroses, thrombocytopenia and thromboembolism can be independent signs of immunologically induced platelet aggregation.

Topics: Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Foot Dermatoses; Heparin; Heparinoids; Heparitin Sulfate; Humans; Kidney Failure, Chronic; Male; Middle Aged; Necrosis; Platelet Aggregation; Renal Dialysis; Skin; Skin Diseases

From three patients with pretibial myxedema (PTM) of Graves' disease, a portion of the skin involved was biopsied, analyzed for proteoglycans and the results were compared with those obtained with euthyroid and hyperthyroid subjects without PTM. The tissue specimen was extracted with 4 M guanidine HCl and subjected to subsequent CsCl density gradient centrifugation. Glycosaminoglycan and protein were recovered in the heaviest density fraction in the three specimens obtained from patients with PTM and not from subjects without PTM. From the analysis by Sepharose CL-6B column, glycosaminoglycan was present as a form of proteoglycan because alkaline borohydride treatment released single chain glycosaminoglycan with a molecular weight of 77,000 or 66,000. The digestion with chondroitin ABC lyase revealed that the majority of proteoglycan in the skin tissue was chondroitin sulfate or dermatan sulfate, and heparan sulfate comprised the minor component (14-34%). The rate of proteoglycan biosynthesis was examined by 35S incorporation into glycosaminoglycan's by cultured fibroblasts from PTM and normal skin. Incorporation of 35S into both proteoglycan and single chain glycosaminoglycan was observed in the fibroblasts of PTM patients as well as of those of subjects without PTM, although the rate of synthesis was more pronounced in the former. The rate of synthesis was influenced neither by normal serum or serum from a pretibial myxedema patient. Since proteoglycan accumulation was detected only in the affected skin of PTM patients, the impairment of local degradation and the proteoglycan clearance mechanism may also be involved.

Topics: Centrifugation, Isopycnic; Chondroitin Sulfates; Graves Disease; Heparitin Sulfate; Humans; Molecular Weight; Myxedema; Proteoglycans; Skin Diseases