ascorbic-acid and Marfan-Syndrome

It is apparent that significant progress has been made in our understanding of the biosynthesis, modifications, and maturation of collagen and elastin. We now recognize and partially understand special reactions involved in hydroxylations within the cell and complex cross-linking processes occurring outside the cell. Recent experiments (191) have shown that in human diploid fibroblast cultures of limited doubling potential (191) the hydroxylation of collagen prolyl residues appears to be "age" or passage-level dependent. With increasing passage level of these cultures, both the ascorbate requirements and the extent of collagen hydroxylation decrease. "Young" cell cultures have a strong requirement for complete hydroxylation and without ascorbate there is only about 50% of the normal level. "Middle-aged" cultures show higher hydroxylation without and full hydroxylation with ascorbate, whereas "old" (or cultures close to "senescence") are incapable of full hydroxylation with or without ascorbic acid. Although the overall system may show some deterioration with increasing passage levels, it appears that with increasing passage levels other components in the cell replace the ascorbate dependence of the hydroxylase system to a greater exten. In some ways, aging WI-38 cultures begin to resemble some transformed cells in their biochemical reactions, although they continue to remain diploid and eventually lose the ability to replicate. It is not yet known whether old animals can produce collagen, which may now be underhydroxylated, perhaps contributing to certain senescent changes. Careful examination of the hydroxylation index of collagen produced in organoid cultures of tissue biopsies as a function of donor age might be informative, particularly if one looks at the quality of collagen by employing collagenase and other proteolytic digests with collagen (191). One could comare the levels of frequent and characteristic peptide triplet sequences such as Gly-Pro-Hyp to Gly-Pro-Pro, Gly-Ala-Hyp to Gly-Ala-Pro, or Gly-Pro-Hyl to Gly-Pro-Lys and others for evaluation of hydroxylation throughout the entire molecule or at selected sequences.

Topics: Amino Acid Sequence; Animals; Antibody Specificity; Ascorbic Acid; Collagen; Connective Tissue; Copper; Ehlers-Danlos Syndrome; Elastin; Epitopes; Homocystinuria; Humans; Hydralazine; Lathyrism; Marfan Syndrome; Molecular Conformation; Platelet Aggregation; Procollagen-Proline Dioxygenase; Skin Diseases; Syndrome

Topics: Adenocarcinoma, Scirrhous; Adult; Amino Acids; Animals; Ascorbic Acid; Cattle; Child; Collagen; Collagen Diseases; Female; Humans; Hydroxyproline; Lung; Marfan Syndrome; Mice; Procollagen-Proline Dioxygenase; Skin Diseases; Stomach Neoplasms

Marfan syndrome (MFS) is associated with progressive aortic dilatation, endothelial dysfunction, and oxidative stress that contribute to the early acute dissection of the vessel and can end up in rupture of the aorta and sudden death. Many studies have described that the organic acids from Hibiscus sabdariffa Linne (HSL) calyces increase cellular antioxidant capacity and decrease oxidative stress. Here we evaluate if the antioxidant properties of HSL infusion improve oxidative stress in MFS patients. Activities of extra cellular super oxide dismutase (ECSOD), glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GSSG-R), glutathione (GSH), lipid peroxidation (LPO) index, total antioxidant capacity (TAC), and ascorbic acid were determined in plasma from MFS patients. Values before and after 3 months of the treatment with 2% HSL infusion were compared in control and MFS subjects. After treatment, there was a significant decrease in ECSOD (p = 0.03), EGPx (p = 0.04), GST (p = 0.03), GSH (p = 0.01), and TAC and ascorbic acid (p = 0.02) but GSSG-R activity (p = 0.04) and LPO (p = 0.02) were increased in MFS patients in comparison to patients receiving the HSL treatment and C subjects. Therefore, the infusion of HSL calyces has antioxidant properties that allow an increase in antioxidant capacity of both the enzymatic and nonenzymatic systems, in the plasma of the MSF patients.

Topics: Adolescent; Adult; Antioxidants; Ascorbic Acid; Child; Female; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Glutathione Transferase; Hibiscus; Humans; Infusion Pumps; Lipid Peroxidation; Male; Marfan Syndrome; Middle Aged; Oxidative Stress; Prospective Studies; Superoxide Dismutase; Young Adult

A female newborn infant with Marfan-like habitus experienced lethargy and hypothermia associated with tyrosinemia that was not corrected by the administration of ascorbic acid at 50 mg/day but that subsequently responded to ascorbic acid at 500 mg/day. Cerebrospinal fluid analysis for neurotransmitter metabolites showed elevated concentrations of homovanillic acid and 5-hydroxyindoleacetic acid when the child was symptomatic and normal concentrations after successful ascrobic acid therapy. These observations suggest that a high level of tyrosine in serum can affect the metabolism in the brain of dopamine and serotonin.

Topics: Ascorbic Acid; Female; Glycols; Homovanillic Acid; Humans; Hydroxyindoleacetic Acid; Infant, Newborn; Infant, Premature; Marfan Syndrome; Methoxyhydroxyphenylglycol; Phenylacetates; Tyrosine