Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036474 (scurvy)
 685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In scorbutic patients, fractures are slow to heal because of impaired collagen synthesis. To investigate the influence of impaired collagen synthesis on the differentiation and proliferation of osteogenic and chondrogenic cells, we examined the expression of genes encoding bone matrix proteins, including osteonectin (ON), osteopontin (OPN), osteocalcin (OC), and matrix Gla protein (MGP), as differentiation markers for osteogenic and chondrogenic cells during fracture healing in Osteogenic Disorder Shionogi (ODS) rats, which have a hereditary defect in the ability to synthesize ascorbic acid (Asc). In ODS rats without Asc supplementation, intramembranous ossification was completely inhibited. Although a few fibroblast-like cells expressing ON mRNA were observed, no OPN mRNA-expressing cells were detected. During endochondral ossification, a small amount of metachromatic staining cartilage appeared at the fracture site, but there was no provisional calcification zone in the cartilage. Chondrocytes expressed ON and MGP mRNAs, but not OPN mRNA. When Asc was given to these rats, callus formation was soon detected around the fracture site, while OPN mRNA was expressed by differentiated osteoblasts and hypertrophic chondrocytes. Our data indicate that impaired collagen synthesis due to Asc deficiency inhibited the increase of ON and MGP mRNA-expressing cells as well as the appearance of OPN mRNA-expressing cells. Since OPN is considered to play an important role in normal and pathological mineralization, lack of OPN mRNA expression accompanying impaired collagen synthesis may have a role in defective mineralization and delayed fracture healing in scurvy.
 ...
PMID:Impaired expression of noncollagenous bone matrix protein mRNAs during fracture healing in ascorbic acid-deficient rats. 949 21

Vitamin C deficiency causes morphologic changes in the endothelial and smooth muscle compartments of guinea pig blood vessels. Endothelial cells synthesize the basement membrane components, type IV collagen and laminin, and smooth muscle cells synthesize elastin in blood vessels. Therefore, we examined the possibility that vitamin C deficiency affects the expression of these proteins. Decreased expression of types I and II collagens in other tissues of vitamin C-deficient guinea pigs is associated with weight loss and the consequent induction of insulin-like growth factor binding proteins; thus we also used food deprivation to induce weight loss. Female guinea pigs received a vitamin C-free diet, supplemented orally with ascorbate. Vitamin C-deficient guinea pigs received the same diet but no ascorbate, and the food-deprived group received no food, but were supplemented with vitamin C. Concentrations of mRNAs for basement membrane components and elastin in blood vessels were measured by Northern blotting; overall basement membrane metabolism was assessed by measuring immunoreactive laminin and type IV 7S collagen in serum. Laminin mRNA in blood vessels and serum laminin concentrations were unaffected by vitamin C deficiency. Concentrations of type IV collagen and elastin mRNAs in blood vessels were not significantly affected in moderately scorbutic guinea pigs (0-7% weight loss), but with increased weight loss, type IV collagen mRNA was 57% (P < 0.05) and elastin mRNA was 3% (P < 0. 01) of normal values. In food-deprived guinea pigs, type IV collagen mRNA was 51% (P < 0.05) and elastin mRNA was 35% (P < 0.05) of normal. Serum type IV 7S collagen concentrations were 25% of normal in scorbutic guinea pigs with extensive weight loss. The lower expression of type IV collagen and elastin mRNAs in blood vessels may contribute to defects observed in blood vessels during scurvy.
 ...
PMID:Vitamin C deficiency in guinea pigs differentially affects the expression of type IV collagen, laminin, and elastin in blood vessels. 991 80

Ascorbic acid (vitamin C) is a cofactor required for the function of several hydroxylases and monooxygenases. It is not synthesized in humans and some other animal species and has to be provided by diet or pharmacologic means. Its absence is responsible for scurvy, a condition related in its initial phases to a defective synthesis of collagen by the reduced function of prolylhydroxylase and production of collagen polypeptides lacking hydroxyproline, therefore, they are unable to assemble into stable triple-helical collagen molecules. In fibroblast cultures, vitamin C also stimulates collagen production by increasing the steady-state level of mRNA of collagen types I and III through enhanced transcription and prolonged half-life of the transcripts. The aim of the experimental work has been to evaluate the effect on dermal cells of a preparation of vitamin C topically applied on one side vs placebo on the other side of the dorsal face of the upper forearm of postmenopausal women. Biopsies were collected on both sides and the level of mRNA measured by non competitive reverse transcription-polymerase chain reaction made quantitative by the simultaneous transcription and amplification of synthetic RNA used as internal standards. The mRNA of collagen type I and type III were increased to a similar extent by vitamin C and that of three post-translational enzymes, the carboxy- and amino-procollagen proteinases and lysyloxidase similarly increased. The mRNA of decorin was also stimulated, but elastin, and fibrillin 1 and 2 were not modified by the vitamin. The expression of matrix metalloproteinases 1, 2, and 9 was not significantly changed, but an increased level of tissue inhibitor of matrix metalloproteinase 1 mRNA was observed without modification of tissue inhibitor of matrix metalloproteinase 2 mRNA. The stimulating activity of topical vitamin C was most conspicuous in the women with the lowest dietary intake of the vitamin and unrelated to the level of actinic damage. The results indicate that the functional activity of the dermal cells is not maximal in postmenopausal women and can be increased.
 ...
PMID:Topically applied vitamin C enhances the mRNA level of collagens I and III, their processing enzymes and tissue inhibitor of matrix metalloproteinase 1 in the human dermis. 1140 71

Vitamin C deficiency or scurvy is a disease now rarely seen except for certain populations at risk. When it occurs, diagnosis can be difficult as it can mimic other disorders. Its manifestations are primarily due to an abnormality in collagen formation causing bleeding in the skin, joints, muscles, or gastrointestinal tract and dystrophic hair deformities. We describe a case of scurvy in a 43-year-old man who presented with new onset hemarthrosis with no history of bleeding disorder. He was found to have perifollicular hyperpigmentation and corkscrew hairs, highly suggestive of scurvy. He admitted to completely eliminating fruits and vegetables from his diet and his serum vitamin C level was markedly decreased. Treatment with daily vitamin C supplement led to relief of symptoms and resolution of skin changes.
 ...
PMID:Hemarthrosis as initial presentation of scurvy. 1218 Jul 58

Iron (II)/2-oxoglutarate (2-OG)-dependent oxygenases catalyse oxidative reactions in a range of metabolic processes including the hydroxylation of proline and lysine residues during the post-translational modification of collagen. 2-OG oxygenases commonly require ascorbate for full activity. In the vitamin C deficient disease, scurvy, reduced activity of 2-OG oxygenases results in impaired formation of collagen. Here we report the crystal structure of bacterial proline 3-hydroxylase from Streptomyces sp., an enzyme which hydroxylates proline at position 3, the first of a 2-OG oxygenase catalysing oxidation of a free alpha-amino acid. Structures were obtained for the enzyme in the absence of iron (to 2.3A resolution, R=20.2%, Rfree=25.3%) and that complexed to iron (II) (to 2.4A resolution, R=19.8%, Rfree=22.6%). The structure contains conserved motifs present in other 2-OG oxygenases including a 'jelly roll' beta strand core and residues binding iron and 2-oxoglutarate, consistent with divergent evolution within the extended family. The structure differs significantly from many other 2-OG oxygenases in possessing a discrete C-terminal helical domain. Analysis of the structure suggests a model for proline binding and a mechanism for uncoupling of proline and 2-OG turnover.
 ...
PMID:Structure of proline 3-hydroxylase. Evolution of the family of 2-oxoglutarate dependent oxygenases. 1173 17

Scurvy is the nutritional deficiency state associated with lowered levels of ascorbic acid (vitamin C). Lack of ascorbic acid leads to suppression of collagen synthesis and the synthesis of defective collagen among other metabolic derangements. Weakening of vascular walls results in signs and symptoms mimicking other diseases such as bleeding diatheses and deep vein thrombosis. Scurvy is rarely encountered in Western countries where there is a broad community understanding of the importance of nutritional requirements and where foods containing ascorbic acid are readily available. As a result of these factors early diagnosis may be hampered where it is not considered in the differential diagnosis, and consequently, prolonged suffering of the patient. Scurvy is easily treated with high doses of oral ascorbic acid, although recurrences may occur. Education of health care providers in recognizing the signs and symptoms of scurvy therefore cannot be over emphasized, particularly in societies in which nutritional deficiencies are considered uncommon. A case of scurvy presenting primarily with oral manifestations is reported here.
 ...
PMID:Oral lesions in scurvy. 1203 65

The only proven requirement for ascorbic acid (vitamin C) is in preventing scurvy, presumably because it is a cofactor for hydroxylases required for post-translational modifications that stabilize collagen. We have created mice deficient in the mouse ortholog (solute carrier family 23 member 1 or Slc23a1) of a rat ascorbic-acid transporter, Svct2 (ref. 4). Cultured embryonic fibroblasts from homozygous Slc23a1(-/-) mice had less than 5% of normal ascorbic-acid uptake. Ascorbic-acid levels were undetectable or markedly reduced in the blood and tissues of Slc23a1(-/-) mice. Prenatal supplementation of pregnant females did not elevate blood ascorbic acid in Slc23a1(-/-) fetuses, suggesting Slc23a1 is important in placental ascorbic-acid transport. Slc23a1(-/-) mice died within a few minutes of birth with respiratory failure and intraparenchymal brain hemorrhage. Lungs showed no postnatal expansion but had normal surfactant protein B levels. Brain hemorrhage was unlikely to be simply a form of scurvy since Slc23a1(-/-) mice showed no hemorrhage in any other tissues and their skin had normal skin 4-hydroxyproline levels despite low ascorbic-acid content. We conclude that Slc23a1 is required for transport of ascorbic acid into many tissues and across the placenta. Deficiency of the transporter is lethal in newborn mice, thereby revealing a previously unrecognized requirement for ascorbic acid in the perinatal period.
 ...
PMID:Ascorbic-acid transporter Slc23a1 is essential for vitamin C transport into the brain and for perinatal survival. 1198 80

The amino acid composition of collagen is described and the status of knowledge about the synthesis of its unique amino acids, hydroxyproline and hydroxylysine, presented. This is followed by a schematic overview of collagen metabolism. Scurvy and lathyrism, the only two abnormalities of collagen metabolism which can now be reasonably elucidated at a molecular level, are then discussed in some detail. The paper concludes by stressing the importance of recognizing the role of histoarchitecture and of interactions of collagen with other compounds when studying collagen or its metabolism in the whole animal.
 ...
PMID:METABOLISM OF COLLAGEN IN MAMMALIAN TISSUES. 1410 82

The changes in scorbutic wounds following the administration of ascorbic acid have been investigated using the techniques of electron microscopy, histochemistry, and autoradioggraphy. Particular attention has been paid to the changes seen in the endoplasmic reticulum of the fibroblasts and to the identity of the extracellular filamentous material characteristic of scorbutic wounds. Seven-day-old wounds in scorbutic guinea pigs were examined prior to and from one to 72 hours following the administration of vitamin C. Fibroblasts from wounds of normal animals demonstrate a characteristic configuration of the ribosomes of the endoplasmic reticulum which is suggested to be analogous to polyribosomes described in cells synthesizing protein such as the reticulocyte. Tangential views of the membranes of the ergastoplasm show the ribosomes to be grouped in paired rows which take both straight and curved paths. This configuration is lost in scurvy and can be seen to begin to reappear as early as 4 hours after giving ascorbic acid. With increasing time, the morphology of the ribosomal aggregates approximates that seen in normal cells, so that by 24 hours their reorientation is complete. It is suggested that one of the disturbances in scurvy may relate to an alteration either in messenger RNA, in the ability of the ribosomes to relate to the messenger, or in the membranes of the ergastoplasm. In addition, the lack of formation of hydroxyamino acids necessary for completing collagen synthesis may be related to the architecture of the ribosomal aggregates. Extracellular collagen fibrils appear concomitant with the restoration of ribosomal and ergastoplasmic morphology as early as 12 hours after administration of ascorbic acid, with complete disappearance of the scorbutic extracellular material within 24 hours. Observations of this scorbutic material do not support the concept that it is a collagen precursor.
 ...
PMID:WOUND HEALING AND COLLAGEN FORMATION. IV. DISTORTION OF RIBOSOMAL PATTERNS OF FIBROBLASTS IN SCURVY. 1420 86

Vitamin C is an essential micronutrient. Absence from the diet will result in the deficiency disease scurvy, typically characterised by weakening of collagenous structures. High intakes of vitamin C have been associated with decreased incidence or severity of a number of diseases, including cancer and cardiovascular disease. These beneficial effects may be attributed to its antioxidant properties, although the exact mechanisms of action remain elusive. It is also unclear what intake levels are required for optimal health benefits. The task of defining optimal intakes is hindered by the lack of a reliable functional marker of tissue vitamin C status in man. Many different pathways have been investigated, but none of them have measurable outcome variables relating directly to scorbutic changes. The bone-collagen formation pathway has the potential to provide a functional index of tissue vitamin C adequacy. Vitamin C acts as a cofactor for the enzyme lysyl hydroxylase, which is required for the hydroxylation of lysine residues in procollagen chains. Pyridinoline is a mature collagen cross-link formed from three hydroxylysine residues, deoxypyridinoline is formed from two hydroxylysine and one lysine residue. Guinea-pig studies have shown an alteration in the pyridinium cross-link ratios in response to graded vitamin C intakes (Tsuchiya & Bates, 1998). In order to investigate whether these changes can be seen in a human population group, a study was carried out in rural Gambia, where there is a marked seasonal variation in dietary vitamin C. The present review discusses the rationale behind the study and presents some preliminary results.
 ...
PMID:Vitamin C and bone markers: investigations in a Gambian population. 1450 91


<< Previous 1 2 3 4 5 6 7 8 9 Next >>