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

Female guinea pigs were fed a scorbutigenic diet supplemented with either L-ascorbic acid or D-isoascorbic acid or combinations of these. Their responses were judged by changes in body weight, serum alkaline phosphatase levels, wound healing, and tooth structure. Large additions (100 mg daily) of D-isoascorbic acid to the scorbutigenic diet resulted in normal growth over a 7-wk period and normal serum alkaline phosphatase levels, tooth structure development, and collagen formation after wounding. The addition of 0.5 or 5.0 mg of L-ascorbic acid to this high D-isoascorbic diet improved neither growth rate nor collagen deposition during wound healing. On the basis of changes in tooth structure, D-isoascorbic acid has 1/20 the potency of L-ascorbic acid. Its effect is additive to subminimal maintenance levels of L-ascorbic acid implying that there is no competitive inhibition in the utilization of the two compounds. The relatively weak activity of D-isoascorbic acid is probably due to poor transport to the tissues and ineffective binding to functional sites. This explains why the onset of scurvy is much more rapid after withdrawal of D-isoascorbic acid from the diet when it had been the sole antiscorbutic dietary constituent. It is concluded that D-isoascorbic acid is a "weakly" antiscorbutic agent on the basis that it is both poorly absorbed and retained by the tissue; that in fact it may, to the degree that it is taken up by the tissues and retained, be equal in antiscorbutic potency to L-ascorbic acid.
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PMID:The antiscorbutic action of L-ascorbic acid and D-isoascorbic acid (erythorbic acid) in the guinea pig. 744 56

Acutely scorbutic and fasted (vitamin C-supplemented) guinea pigs exhibit decreased collagen gene expression associated with weight loss. We recently demonstrated that circulating insulin-like growth factor-binding protein-1 and -2 (IGFBP-1 and -2) are induced in these deficiencies, and that removal of IGFBP-1 and -2 from serum of such animals by specific antibodies reverses inhibition of cellular IGF-I-dependent functions, including collagen and DNA synthesis. Here we investigated the kinetics of induction of IGFBP-1 and -2 relative to suppression of collagen gene expression. Guinea pigs were fasted for 10-96 h, with 3-24% weight loss, or received an ascorbate-free diet for up to 4 weeks, with 5-28% weight loss during the third and fourth weeks (phase II of scurvy). In both deficiencies, there was noncoordinate regulation of collagen mRNA expression in tissues. Type I collagen mRNA concentrations in skin decreased rapidly after 5-10% weight loss and reached about 10% of normal levels, whereas in bone, there was a later, and not as extensive, decrease. The concentration of cartilage type II collagen mRNA decreased rapidly initially, but then remained at 40-50% of normal. Circulating IGF-I concentrations remained normal during the period when collagen gene expression was initially suppressed, although there was a later decrease. In contrast, mRNAs for IGFBP-1 and -2 and the circulating proteins were induced before or concomitantly with the suppression of collagen gene expression. The ability of fasted or scorbutic guinea pig sera to inhibit IGF-I action in cells increased in parallel with IGFBP activity ([125I]IGF-I binding), which, in turn, mainly reflected the concentration of IGFBP-1 in sera. Serum insulin may be the primary regulator of the IGFBPs. Its levels were decreased to 10-13% of normal when weight loss commenced, whereas cortisol levels, although increased, did not correlate with the induction of IGFBPs. The overall results taken together with our recent findings from cell culture experiments are compatible with circulating IGFBP-1 and -2 acting as inhibitors of collagen gene expression by blocking IGF-I action during fasting and phase II of vitamin C deficiency.
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PMID:Evidence for an in vivo role of insulin-like growth factor-binding protein-1 and -2 as inhibitors of collagen gene expression in vitamin C-deficient and fasted guinea pigs. 750 38

A better understanding of the functions of ascorbic acid would help clarify the magnitude of the influence of this vitamin on health-related conditions. Many of the purported benefits require confirmation as well as a knowledge of the mechanism of action. The majority of investigations of the association of vitamin C with various types of cancer, with cardiovascular risk, and with cataract formation were epidemiologic studies. Often it was not possible to discern whether the apparent protective effect was due to vitamin C, vitamin E, or carotene, or to a combined effect of these nutrients or of additional factors. Human intervention trials may provide definitive and quantitative assessments of the role of vitamin C in health maintenance. We need to gain a more thorough understanding of the interactions of vitamin C with other nutrients, such as vitamin E and carotenoids, in order to appreciate the role of vitamin C in disease prevention. Investigators are increasingly recognizing the diverse functions of vitamin C in the body in addition to its role in collagen synthesis. However, the functional consequences of these many important roles of vitamin C remain essentially unknown. Excluding scurvy, the health consequences of inadequate vitamin C status are not well characterized. Nonetheless, epidemiologic evidence suggests a role for vitamin C in cancer and heart disease as well as in a number of other diseases.
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PMID:Pharmacology of vitamin C. 794 25

There is an enormous amount of literature on vitamin C intake and health in animals, cell cultures, and humans. Beyond its function in collagen formation, ascorbic acid is known to increase absorption of inorganic iron, to have essential roles in the metabolism of folic acid and of some amino acids and hormones, and to act as an antioxidant. In recent years, research has increasingly focused on this latter function, stimulated by suggestions that "oxidative stress" may be a causal factor in the etiology of such diverse and important disorders of aging as cancer, cardiovascular disease, and cataract formation. The present evidence is strong enough to have convinced nutritionists that daily vitamin C intake should be many times higher than the amount needed to protect against scurvy, and this is reflected in the present Recommended Dietary Allowances. Suggestions that the recommended levels should be higher still are largely based on extrapolations from results of animal and tissue culture studies. How much ascorbic acid is necessary to achieve in humans the effects seen in animal studies is not clear. In general, the limited human studies have not been persuasive. The data are incomplete, and many of the studies have serious flaws. There are no toxicity studies of the type done for new compounds being considered for approval as therapy for major disease conditions. Intervention studies will be difficult, but are essential, and methods for tissue saturation measurement must be defined before new recommendations for the public are designed.
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PMID:Vitamin C (ascorbic acid): new roles, new requirements? 805 61

Muscle may suffer from a number of diseases or disorders, some being fatal to humans and animals. Their management or treatment depends on correct diagnosis. Although no single method may be used to identify all diseases, recognition depends on the following diagnostic procedures: (1) history and clinical examination, (2) blood biochemistry, (3) electromyography, (4) muscle biopsy, (5) nuclear magnetic resonance, (6) measurement of muscle cross-sectional area, (7) tests of muscle function, (8) provocation tests, and (9) studies on protein turnover. One or all of these procedures may prove helpful in diagnosis, but even then identification of the disorder may not be possible. Nevertheless, each of these procedures can provide useful information. Among the most common diseases in muscle are the muscular dystrophies, in which the newly identified muscle protein dystrophin is either absent or present at less than normal amounts in both Duchenne and Becker's muscular dystrophy. Although the identification of dystrophin represents a major breakthrough, treatment has not progressed to the experimental stage. Other major diseases of muscle include the inflammatory myopathies and neuropathies. Atrophy and hypertrophy of muscle and the relationship of aging, exercise, and fatigue all add to our understanding of the behavior of normal and abnormal muscle. Some other interesting related diseases and disorders of muscle include myasthenia gravis, muscular dysgenesis, and myclonus. Disorders of energy metabolism include those caused by abnormal glycolysis (Von Gierke's, Pompe's, Cori-Forbes, Andersen's, McArdle's, Hers', and Tauri's diseases) and by the acquired diseases of glycolysis (disorders of mitochondrial oxidation). Still other diseases associated with abnormal energy metabolism include lipid-related disorders (carnitine and carnitine palmitoyl-transferase deficiencies) and myotonic syndromes (myotonia congenita, paramyotonia congenita, hypokalemic and hyperkalemic periodic paralysis, and malignant hyperexia). Diseases of the connective tissues discussed include those of nutritional origin (scurvy, lathyrism, starvation, and protein deficiency), the genetic diseases (dermatosparaxis, Ehlers-Danlos syndrome, osteogenesis imperfecta, Marfan syndrome, homocystinuria, alcaptonuria, epidermolysis bullosa, rheumatoid arthritis in humans, polyarthritis in swine, Aleutian disease of mink, and the several types of systemic lupus erythematosus) and the acquired diseases of connective tissues (abnormal calcification, systemic sclerosis, interstitial lung disease, hepatic fibrosis, and carcinomas of the connective tissues). Several of the diseases of connective tissues may prove to be useful models for determining the relationship of collagen to meat tenderness and its other physical properties. Several other promising models for studying the nutrition-related disorders and the quality-related characteristics of meat are also reviewed.
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PMID:Diseases and disorders of muscle. 839 47

The regulation of expression of hepatic iron-related proteins was examined during iron deficiency caused by scurvy in guinea pigs. Previous studies showed that some effects of scurvy, such as suppression of collagen gene expression, result from events associated with weight loss. During the initial phase of scurvy when vitamin C is depleted but animals grow normally, serum iron levels decreased to 50% of normal. During the second phase of scurvy when animals lose weight, there was a further decrease in iron levels to 10-15% of normal. Serum transferrin levels increased during scurvy, but this increase was related neither to the rate of weight loss nor to hepatic transferrin mRNA expression, which decreased. Serum ferritin levels of diminished early in scurvy with a preferential loss of the L subunit. In liver, however, both ferritin animals gaining weight. Ferritin gene expression during vitamin C deficiency was correlated with serum ferritin levels in that the level of mRNA for the H subunit remained relatively constant while that of the L subunit decreased early. Transferrin receptor mRNA expression in liver was induced as soon as iron levels decreased early in scurvy, which is similar to results reported for iron-depleted cultured cells. In contrast to results in cell culture, expression of iron regulatory protein 1 mRNA was decreased to approximately 50% of normal early in scurvy with a concomitant decrease in hepatic cytosolic aconitase activity. Our data indicate that iron deficiency occurs early during vitamin C deficiency and leads to changes in expression of iron-related proteins that differ in some aspects from regulation by iron in cell culture. Other events associated with weight loss in late scurvy may play a further role in this regulation.
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PMID:Gene expression of iron-related proteins during iron deficiency caused by scurvy in guinea pigs. 856 10

Latent scurvy is characterized by a reversible atherosclerosis that closely resembles the clinical form of this disease. Acute scurvy is characterized by microvascular complications such as widespread capillary hemorrhaging. Vitamin C (ascorbate) is required for the synthesis of collagen, the protein most critical in the maintenance of vascular integrity. We suggest that in latent scurvy, large blood vessels use modified LDL--in particular lipoprotein(a)--in addition to collagen to maintain macrovascular integrity. By this mechanism, collagen is spared for the maintenance of capillaries, the sites of gas and nutrient exchange. The foam-cell phenotype of atherosclerosis is identified as a mesenchymal genetic program, regulated by the availability of ascorbate. When vitamin C is limited, foam cells develop and induce oxidative modification of LDL, thereby stabilizing large blood vessels via the deposition of LDL. The structural similarity between vitamin C and glucose suggests that hyperglycemia will inhibit cellular uptake of ascorbate, inducing local vitamin C deficiency.
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PMID:Hyperglycemia-induced latent scurvy and atherosclerosis: the scorbutic-metaplasia hypothesis. 869 35

The effect of severe ascorbic acid deficiency on bone remodeling and collagen synthesis was evaluated in a 21 day experiment, using the scorbutic guinea pig model. Animals (n = 6-7/group) were assigned to one of three groups: scorbutic, pair-fed ascorbic acid-replete, or ad libitum ascorbic acid-replete groups. After 2 weeks, scorbutic animals started voluntarily decreasing food intake and losing weight. By day 19-21, at which time bone and tissue samples were collected and analyzed, scorbutic animals decreased food intake to 46% of usual and lost 9% body weight. Serum 25OHD3, 1,25(OH)2D3, calcium, and albumin were significantly lower (p < 0.05) in the scorbutic animals than in the other groups. Bone mineral density and bone mineral content of the proximal and central femur were significantly lower in the scorbutic group than in the other groups (p < 0.05). Morphometric analysis of tibia indicated significantly lower bone volume, fewer and thinner trabeculae, and a thinner growth plate in the scorbutic group, compared to the pair-fed and ad libitum groups (p < 0.05). Osteoclast surface was about 60% higher in the scorbutic group than in the pair-fed and ad libitum control groups (0.05 < p < 0.10). Mechanical strength of the femur and lumbar vertebral body tended to be lower when bone mass was altered in the same group. Collagen synthesis of articular cartilage and tendons was lower in the scorbutic group than in the pair-fed or ad libitum groups (p < 0.05). In conclusion, scurvy but not food restriction, per se, results in alterations in bone mass and tissue collagen synthesis.
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PMID:Scurvy results in decreased collagen synthesis and bone density in the guinea pig animal model. 870 85

The precise physiological role of alkaline phosphatase is unknown, although evidence suggests it is involved in bone mineralization. Previous studies showed that serum and bone alkaline phosphatase activity is decreased during vitamin C deficiency. Some effects of scurvy, such as inhibition of collagen synthesis, are related to weight loss and subsequent induction of insulin-like growth factor binding proteins and they can be duplicated in fasted guinea pigs receiving vitamin C. We found that decreased alkaline phosphatase activity in bone and serum during scurvy was not completely due to the "fasting effect" and that the decrease in serum was due to loss of bone isoenzyme activity. There also was a decrease in immunoreactive enzyme protein and alkaline phosphatase mRNA concentrations in bone of scorbutic animals, indicating that synthesis of the enzyme was inhibited. Sialylation and addition of the glycosylphosphatidylinositol anchor to the enzyme in bone tissue were not affected by scurvy. The concentration of mRNA for osteocalcin, a bone-specific marker, also fell during scurvy and to a much greater extent than either alkaline phosphatase or type I collagen mRNAs, while osteopontin mRNA concentrations increased. These results differ from the reported role of ascorbic acid on the pattern of expression of these proteins during differentiation of osteoblasts in culture. The decreased expression of collagen, alkaline phosphatase, and osteocalcin could explain the defects in bone caused by scurvy.
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PMID:Regulation and properties of bone alkaline phosphatase during vitamin C deficiency in guinea pigs. 895 Oct 38

Although gingival bleeding is a manifestation of both scurvy and inflammatory periodontal disease, the two conditions are distinctly separate entities. The defective collagen synthesis associated with scurvy also manifests many of the same symptoms as deficient vitamin C physiology, but neither condition is associated with periodontal disease. Unlike scurvy, the various periodontal diseases are caused by oral plaque microorganisms. The body's reaction to these microorganisms is strongly influenced by the compromised functioning of leucocytes and monocytes. Although certain infections and systemic diseases cause gingival bleeding, avitaminosis-C does not cause commonly encountered periodontitis. Vitamin C should not be used for the prophylaxis or cure of periodontal disease in otherwise healthy, well-nourished individuals. A patient with bleeding gingivae warrants referral to a periodontist, oral medicine specialist, or appropriately qualified dentist for examination and treatment.
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PMID:Oral scurvy and periodontal disease. 943 25


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