chondroitin-sulfates and Cleft-Palate

Ankyloblepharon-ectodermal defect-cleft lip and/or palate (AEC syndrome, also known as Hay-Wells syndrome) is an autosomal dominant disease caused by mutation in the p63 gene that is primarily characterized by facial clefting, presence of ankyloblepharon, ectodermal dysplasia, and scalp erosion. Scalp erosion is perhaps the most debilitating manifestation of AEC due to its problematic treatment that is fraught with failure given the underlying pathology of the p63 mutation causing dysfunctional wound healing. Management is often targeted in a stepwise fashion, beginning with daily baths, light debridement, and emollients and progressing to extensive skin excision. Skin grafting has limited success and, inevitably, infections requiring aggressive debridement and antibiotic therapy result from dysfunctional healing. The use of acellular dermal matrix for treatment of scalp erosion is a novel approach attempted in a patient with severe scalp disease. Here we report her case and the failure of treatment, along with possible explanations and suggestions for future therapy.

Topics: Anti-Bacterial Agents; Bandages; Chondroitin Sulfates; Cleft Lip; Cleft Palate; Collagen; Debridement; Ectodermal Dysplasia; Emollients; Eye Abnormalities; Eyelids; Female; Glucocorticoids; Humans; Infant; Scalp; Therapeutic Irrigation

Our aim was to compare the dentoalveolar development in beagle dogs after palatal repair according to the Von Langenbeck technique with and without implantation of a dermal substitute.. Nineteen beagles (age, 12 weeks) were assigned to 2 experimental groups and an untreated control group. Palatal surgery was performed with the Von Langenbeck technique in the 2 experimental groups. The dermal substitute Integra (Plainsboro, NJ, USA) was implanted in 1 experimental group, and the other served as sham group. Dental casts were made before surgery and at several times in all groups to measure dentoalveolar development. Transversal distances, arch depth, tipping, and rotation were determined. Histologic evaluations were performed at 3, 7, and 15 weeks after surgery. The degrees of reepithelialization and tissue organization were evaluated microscopically.. All wounds healed without complications. Scar tissue attached to the bone was found in both experimental groups. Deposition of bone in the Integra occurred after implantation, indicating its osteoconductivity. Transversal dentoalveolar development was similar in both experimental groups, but it was significantly less than in the control group.. Implantation of Integra after the Von Langenbeck procedure for palatal repair does not improve dentoalveolar development.

Topics: Alveolar Process; Animals; Chondroitin Sulfates; Cleft Palate; Collagen; Dogs; Oral Surgical Procedures; Plastic Surgery Procedures; Random Allocation; Skin, Artificial; Surgical Flaps; Tooth; Treatment Outcome

During embryonic development, the proper production of extracellular matrix molecules mediates morphogenetic processes involved in palatogenesis. In the present study, we investigated whether any differences exist in glycosaminoglycan (GAG) and collagen synthesis between palate fibroblasts from infants, with or without cleft palate, in two age ranges. Subsequently, the effects of diphenylhydantoin (PHT), a teratogen known to induce cleft palate in human and mammalian newborns, on extracellular matrix (ECM) production were studied. We found that cleft palate fibroblasts (CPFs) synthesize greater amounts of GAG and collagen than normal fibroblasts (NFs). CPFs produced less cellular hyaluronic acid (HA) and more sulphated GAG. HA was the principal GAG species in the medium, and its percentage was lower in one- to three-year-old CPFs. Cleft palate fibroblasts produced more extracellular chondroitin 4- and 6-sulphate (CS) and dermatan sulphate (DS). Associated with a higher production of sulphated GAG, we observed a higher synthesis of type III and type I collagen with a normal ratio of alpha2(I) to alpha1(I) chains. PHT treatment of NFs reduced collagen and GAG synthesis, with a marked effect on sulphated GAG. The drug changed collagen synthesis, whereas it did not affect GAG production in CPFs whose phenotype may already be impaired. These findings indicate that, in CPFs, modifications in the pattern of ECM components, which are most likely responsible for the anomalous development, persist in infants. In addition, NFs and CPFs with a different phenotype respond differently to PHT treatment.

Topics: Cells, Cultured; Child; Child, Preschool; Chondroitin Sulfates; Cleft Palate; Collagen; Dermatan Sulfate; Extracellular Matrix Proteins; Fibroblasts; Glycosaminoglycans; Heparitin Sulfate; Humans; Hyaluronic Acid; Infant; Palate; Phenytoin

The biosynthesis and hydration of glycosaminoglycans (GAG) has been implicated in the generation of palatal shelf-elevating force(s) in mammals, although the nature of the palatal shelf extracellular matrices during cleft palate formation remains poorly understood. This study quantifies the GAG composition in the palatal shelves of Wistar rat fetuses at various periods of palatogenesis where clefts were induced experimentally using 5-fluoro-2-deoxyuridine (FUDR). For both normal and cleft palatal shelves, hyaluronan, heparan sulphate and chondroitin-4-sulphate were detected but not dermatan sulphate or chondroitin-6-sulphate. Throughout the period of cleft development studied, the total amount of GAG was significantly decreased (by approx. 30%) compared with normal development, this decrease being particularly marked at a time equivalent to post-elevation during normal development (approx. 75%). Furthermore, and unlike normal palatogenesis, no significant differences were recorded between the anterior and posterior parts of the palatal shelves during cleft formation. As for normal palatogenesis, however, the percentages of each GAG were not altered at any stage. The findings are consistent with the view that suppression of GAG biosynthesis is related to the development of cleft palate in FUDR-treated rat fetuses and can therefore be interpreted as providing evidence of a role for the mesenchymal glycoconjugates in shelf elevation during normal palatogenesis.

Topics: Animals; Chondroitin Sulfates; Cleft Palate; Densitometry; Dermatan Sulfate; Electrophoresis, Cellulose Acetate; Extracellular Matrix; Fetus; Floxuridine; Glycosaminoglycans; Heparitin Sulfate; Hyaluronic Acid; Mesoderm; Palate; Palate, Soft; Rats; Rats, Wistar

Administration of the cleft palate teratogen chlorcyclizine or norchlorcyclizine to pregnant rats causes an alteration in glycosaminoglycans (GAGs) in embryonic palatal shelves. Pulse-chase experiments in vitro indicate that norchlorcyclizine enhances the degradation of hyaluronic acid and chondroitin sulfate but has little or no effect on their synthesis. These changes in GAGs are caused by concentrations of norchlorcyclizine that have no appreciable effect on DNA or protein synthesis. These findings suggest that degradation of palatal GAGs may be the primary biochemical defect responsible for the inhibition of palatal shelf elevation by norchlorcyclizine.

Topics: Abnormalities, Drug-Induced; Animals; Chondroitin Sulfates; Cleft Palate; DNA; Female; Germ Layers; Glycosaminoglycans; Hyaluronic Acid; Palate; Piperazines; Pregnancy; Protein Biosynthesis; Rats