ascorbic-acid and Osteogenesis-Imperfecta

Topics: Ascorbic Acid; Calcitonin; Calcium; Catechin; Cholecalciferol; Hormones; Humans; Magnesium Oxide; Osteogenesis Imperfecta; Sodium Fluoride

Vitamins are playing an increasingly important role in "malattie evolutive", both in the newer sense meaning diseases connected with general development and in the original sense of progressive diseases. Examples of the preventive use of vitamins in certain development phases are the prophylactic administration of vitamin E in premature and new-born babies as protection against retrolental fibroplasia, vitamin K against haemorrhage and vitamin D against bone deformation. Deficient ossification in osteogenesis imperfecta can be prevented by high doses of vitamin C. Recently, greater medical interest has centred around the preventive use of high vitamin dosage in "malattie evolutive" in the original sense. Here, the main interest has been in vitamins E and C which, as recent investigations show, are capable of retarding or preventing deleterious cardiovascular or oncological diseases.

Topics: Adolescent; Aorta; Ascorbic Acid; Blood Glucose; Cerebrovascular Disorders; Child; Child, Preschool; Cholesterol; Clinical Trials as Topic; Double-Blind Method; Female; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Lipids; Male; Osteogenesis Imperfecta; Vitamins

Various mutations of genes encoding type I procollagen chains have been linked to osteogenesis imperfecta (OI). The mutations yield abnormal procollagen molecules that fold improperly. HSP 47, a stress-inducible protein localized to the endoplasmic reticulum (ER) of collagen-producing cells, may participate in collagen processing as a procollagen-specific molecular chaperone. The intracellular transport of abnormal procollagen molecules and the expression of HSP 47 have been studied in fibroblasts from a patient with OI. Normal and OI fibroblasts cultured with or without ascorbate were analysed by immunofluorescent double labelling with monoclonal antibodies to C-propeptide of type I procollagen and HSP 47, as observed by confocal microscopy. Procollagen and HSP 47 were also quantified by immunoprecipitation of normal and OI fibroblasts radiolabelled with 35S-methionine. By confocal microscopy, procollagen molecules were retained in the ER of both fibroblast types cultured in the absence of ascorbate, and were co-localized with HSP 47. In normal fibroblasts, 2 h after the addition of ascorbate, most of the procollagen had disappeared from the cells, while in OI fibroblasts, abnormal procollagen molecules and HSP 47 were still retained in the ER. By immunoprecipitation, procollagen was negligible in normal fibroblasts cultured with ascorbate; much larger amounts of procollagen were immunoprecipitated from OI fibroblasts despite ascorbate. Increased HSP 47 in OI fibroblasts was demonstrated by immunoprecipitation with a specific monoclonal antibody. These results suggest the increase in HSP 47 in the ER of OI fibroblasts is related to its collagen-specific chaperone function.

Topics: Ascorbic Acid; Cell Culture Techniques; Fatal Outcome; Fibroblasts; Fluorescent Antibody Technique; Heat-Shock Proteins; HSP47 Heat-Shock Proteins; Humans; Infant; Microscopy, Confocal; Osteogenesis Imperfecta; Procollagen; Radiography; Radioimmunoprecipitation Assay

Of 20 fibroblast cell strains from patients with osteogenesis imperfecta (OI), a disease caused by mutations in the genes encoding type I procollagen, three had increased synthesis of BiP (GRP78), an hsp70-related, endoplasmic reticulum-resident protein. All three strains carry unique mutations in pro alpha 1(I) chains which impair type I procollagen chain association. Immunoprecipitation and pulse-chase experiments show that BiP (immunoglobulin heavy chain-binding protein) stably binds pro alpha 1(I) chains in these three cell strains after a brief lag. Ascorbate, which increases procollagen synthesis, increases BiP synthesis and content in these three strains and not in the others. In one of these three strains, BiP content is constitutively elevated prior to ascorbate treatment, and BiP is less inducible. This strain also has relatively high levels of synthesis and content of GRP94, another endoplasmic reticulum-resident stress protein. Pretreating each of the three cell strains to increase their BiP content reduces subsequent ascorbate-mediated BiP induction. BiP synthesis in the 17 other OI strains examined, which had a variety of type I procollagen mutations, was normal. These results suggest that BiP is induced by and binds procollagen with specific types of mutations: ones in the carboxyl-terminal propeptide that interfere with chain association. The recognition by BiP of such procollagen in OI cell strains shows that BiP plays a role in the physiological response to the production of some disease-producing abnormal proteins.

Topics: 2,2'-Dipyridyl; Amino Acid Sequence; Ascorbic Acid; Carrier Proteins; Cells, Cultured; Endoplasmic Reticulum Chaperone BiP; Female; Fetal Death; Fibroblasts; Heat-Shock Proteins; Humans; Infant, Newborn; Infant, Premature; Kinetics; Macromolecular Substances; Molecular Chaperones; Molecular Weight; Osteogenesis Imperfecta; Point Mutation; Procollagen; Protein Binding; Skin

Topics: Adolescent; Adult; Ascorbic Acid; Back Pain; Bone Diseases; Child; Fractures, Bone; Humans; Muscular Diseases; Neoplasms; Osteogenesis Imperfecta; Pain

Topics: Ascorbic Acid; Bone Nails; Child; Collagen; Dose-Response Relationship, Drug; Female; Femoral Fractures; Fracture Fixation, Internal; Fractures, Spontaneous; Humans; Osteogenesis Imperfecta

Topics: Ascorbic Acid; Calcitonin; Child; Child, Preschool; Female; Fluorides; Humans; Infant; Male; Osteogenesis Imperfecta; Sodium Fluoride

Topics: Ascorbic Acid; Calcitonin; Calcium; Child; Humans; Male; Osteogenesis Imperfecta; Vitamin D

The treatment of osteogenesis imperfecta with magnesium is theoreticaly sound, but usually works in a few individuals. There are greater expectations with calcitonin, which reduces the overall osteolysis. The treatment of fractures should, whenever possible, be concervative. Internal fixation by plates is not indicated, because the plate should span from metaphysis to metyphysis, which leads to a softeming of the underlying cortex. Because of the weak bone, srews do not hold well. For operative treatment of the lower limb, the Küntscher nail is the fixation of choice, as well as for treatment of deformity by multiple fragmentation. Rapidly progressive scoliosis should be treated operatively from 9 years of age on.

Topics: Age Factors; Ascorbic Acid; Bone Nails; Calcitonin; Child; Fracture Fixation; Fracture Fixation, Intramedullary; Fractures, Spontaneous; Humans; Infant; Magnesium; Osteogenesis Imperfecta; Osteolysis; Scoliosis

Topics: Ascorbic Acid; Calcitonin; Calcium; Calcium, Dietary; Humans; Osteogenesis Imperfecta; Vitamin D

Topics: Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Ascorbic Acid; Cat Diseases; Cats; Dietary Proteins; Meat; Nutrition Disorders; Nutritional Requirements; Osteogenesis Imperfecta; Plant Proteins, Dietary; Riboflavin Deficiency; Rickets; Thiamine Deficiency; Urinary Calculi; Vitamin A; Vitamin A Deficiency; Vitamin B 6 Deficiency; Vitamin D Deficiency; Vitamin E Deficiency

Topics: Administration, Oral; Adolescent; Ascorbic Acid; Child; Child, Preschool; Female; Fractures, Bone; Humans; Infant; Infant, Newborn; Male; Osteogenesis Imperfecta; Zinc

Topics: Adolescent; Adult; Ascorbic Acid; Child; Child, Preschool; Humans; Osteogenesis Imperfecta

Topics: Acid Phosphatase; Adolescent; Adult; Ascorbic Acid; Blood Protein Electrophoresis; Carotenoids; Child; Child, Preschool; Female; Glycoproteins; Humans; Immunoelectrophoresis; Male; Middle Aged; Osteogenesis Imperfecta; Oxalates; Vitamin A