Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003969 (vitamin C deficiency)
 625 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitochondrial glycerol 3-phosphate dehydrogenase (mGPDH) from control and scorbutic guinea pig brain, liver and skeletal muscle and from normal rat liver was stimulated several fold by l-ascorbic acid (AA). The amount of AA that gave half-maximal stimulation of guinea pig brain mGPDH was 7.1 microM. At concentrations of AA higher than 500 microM, mGPDH activity decreased to nearly the same activity as in the absence of AA. D-Ascorbic acid, erythorbic acid, was equally potent in the activation of washed mitochondrial mGPDH activity. The AA activation of mGPDH was completely inhibited by 50 microM EGTA, but could be fully restored by the sequential addition of 100 microM Ca2+. The AA activation of mGPDH was likewise completely inhibited by iron specific chelators, bathophenanthrolinedisulfonic acid, desferrioxamine, and 1,10-phenanthroline, but the activation could not be restored by the addition of excess Ca2+. In the absence of AA, mGPDH activity was not inhibited by either EGTA or the iron chelators and Ca2+ addition had no effect on the activity. The iron-sulfur protein, succinic dehydrogenase (complex II), was not significantly different in brain mitochondria from control or scorbutic guinea pigs, and was not activated by the subsequent addition of AA. In the presence of AA, succinic dehydrogenase activity was not affected by either bathophenanthrolinedisulfonic acid or EGTA. The results suggest that mGPDH is a probable site of action of AA in the related glucose-coupled insulin release from pancreatic islets.
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PMID:Ascorbic acid is a stimulatory cofactor for mitochondrial glycerol-3-phosphate dehydrogenase. 934 51

Data suggest a large variability in the effectiveness of the orally active iron chelator, deferiprone, in inducing a sustained decrease in body iron to concentrations compatible with the avoidance of complications from iron overload. We analyzed 19 patients with thalassemia major who were undergoing long-term therapy with deferiprone (75 mg/kg/day every 8 hours). In seven of the 19 patients, hepatic iron concentration had been reduced or maintained at less than 7 mg/g of dry weight liver tissue, associated with no evidence of iron-induced toxicity (group A). In the remaining 12, hepatic iron concentration had either stabilized at higher than 7 mg/g of dry weight liver tissue, or increased to such concentrations during therapy with deferiprone (group B). We studied in these patients determinants that may explain such variability, including initial hepatic iron concentrations, compliance, transfusion index, pharmacokinetic characteristics of deferiprone, and plasma vitamin C status. Patients in group B showed significantly decreased plasma vitamin C concentrations compared with those in group A, who demonstrated normal levels (0.04 mg/dl [0.04-0.19 mg/dl] and 0.62 mg/day [0.44-1.05 mg/day], respectively; p = 0.02). A significant difference in apparent volume of distribution (Vd/F) had developed between the groups over time, with a higher Vd/F in group B (1.66 [0.681, group A] and 3.16 [0.811, group B]; p = 0.006). Group B had started with hepatic iron concentrations that were significantly higher than those of group A, a difference that became more pronounced over time. In the initial analysis, serum ferritin concentrations were also higher in group B. The two groups did not differ in the remaining factors. The initial hepatic iron concentrations predicted the slope of change in this value. Regression analysis suggested that patients with initial hepatic iron concentration of less than or equal to 7.22 mg/g of dry weight liver tissue are unlikely to further decrease while taking deferiprone 75 mg/kg/day. Vitamin C deficiency developed in patients in group B over time. Vitamin C is an important biologic cofactor that plays a role in the distribution of iron. The trend of increase in Vd/F of deferiprone over time may imply a compartment shift of iron stores to one less accessed by deferiprone. This study confirmed the effectiveness of deferiprone in heavily iron-loaded patients and provided evidence that its effectiveness decreases in proportion to liver iron load.
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PMID:An investigation into variability in the therapeutic response to deferiprone in patients with thalassemia major. 3076 96

Adjuvant therapy may allow patients being treated with epoetin to derive greater clinical benefits. Iron supplementation is currently the most widely used form of adjuvant therapy; intravenous (i.v.) iron is required by the majority of haemodialysis patients receiving epoetin. Measurement of hypochromic red blood cells is the most direct way of assessing iron supply to the bone marrow. During the correction phase, a dose of i.v. iron equivalent to 50 mg/day is recommended, with the total dose not exceeding 3 g. When subclinical vitamin C deficiency is suspected, ascorbic acid may be given orally (1-1.5 g/week) or i.v. (300 mg three times weekly at the end of dialysis). The active vitamin D metabolites alfacalcidol and calcitriol may, under some circumstances, improve anaemia and reduce epoetin dosage requirements. Vitamin B6 requirements are increased during epoetin therapy, and supplementation at a dose of 100-150 mg/week is recommended. Supplementation of vitamin B12 is optional. Folic acid is supplemented routinely in haemodialysis patients, though evidence that it increases the efficacy of epoetin is limited. Low doses (2-3 mg/week) should normally be sufficient to maintain optimal folic acid stores in epoetin-treated patients, although higher doses are necessary for patients with hyperhomocysteinaemia. L-Carnitine supplementation may be appropriate in some patients with anaemia of chronic renal failure (CRF) unresponsive to, or requiring large doses of, epoetin. Androgens potentially could reduce epoetin costs in countries with limited resources, but should only be used in men older than 50 years with a remnant kidney. Recent animal studies indicate that the combination of epoetin and insulin-like growth factor 1 might be beneficial in CRF patients. High doses of angiotensin-converting enzyme (ACE) inhibitors should be reserved for dialysis patients who have hypertension that cannot be controlled by other agents, or who require an ACE inhibitor for treatment of heart failure.
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PMID:Is there a role for adjuvant therapy in patients being treated with epoetin? 1057 78

Effects of deficiency of vitamins on early development of brain have been reviewed. Unusual developmental problems in neurogenesis specific for the brain and impairment of its functional capacities due to vitamin deficiency have been discussed. The species-specific "critical periods" in development of various systems have been mentioned. Indices such as reflex activity, locomotion, special senses, cognition and adaptive behavior were used for assessing brain maturation in experimental models and humans. Significant examples include brain anomalies in humans and other mammals caused by retinoid excess or deficit; increase in calbindin D28K, a vitamin D dependent calcium-binding protein during postnatal period in rat; hydrocephalus and exencephaly in prenatal rats and subarachnoidal or intracerebral hemorrhage in infants caused by vitamin E deficiency. Peripheral neuropathic lesions leading to infantile beriberi is caused by thiamine deficiency. Impaired growth in retinal layers leading to delay in maturation of electroretinogram and depth-perception in postnatal rats occur due to pyridoxine deficiency. Infants of severely vitamin B12 deficient mothers show abnormalities in behavior involving basal ganglia and pyramidal tract. Folic acid deficiency results in delayed maturation of the basic electroencepalographic patterns. In addition, vitamin-interactions leading to developmental errors have been pointed out. Vitamin B6 deficiency impairs vitamin B12 absorption and biotin deficiency may be aggravated by pantothenic acid deficiency. Vitamin C deficiency resulting in impaired metabolism may produce symptoms of deficiency of folic acid. Another characteristic examples is that iron absorption from dietary sources is dependent on ascorbic acid.
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PMID:Vitamins and brain development. 1052 53

I.v. ascorbic acid has been used in an effort to mobilize ferritin stores in hyporesponsive HD patients receiving Epoetin alfa. However, not all patients who respond to i.v. ascorbic acid therapy will have subsequent decline in feritin stores (Gastaldello et al., 1995; Tarng & Huang, 1998). Additionally, predicting those patients who will overcome their Epoetin alfa hyporesponsiveness remains unclear. Ascorbic acid's effect on hemosiderin deposits may be another possible mechanism to the increased Epoetin alfa response observed in some HD patients (Hemosiderin is a pathologic deposition of iron in tissues including the spleen, small intestine, and bone marrow). Although there are no well-controlled studies evaluating hemosiderin and i.v. ascorbic acid, it should be noted that subjects with scurvy often present with excessive iron deposits in the tissues, indicating the possible effects of ascorbic acid on hemosiderin metabolism (Bothwell et al., 1964). Ascorbic acid deficiency is often present in many HD patients due to its removal during dialysis and lack of dietary intake (Ponka & Kuhlback, 1983). It remains controversial whether oral ascorbic acid supplementation is indicated in patients receiving HD. Therefore, the Recommended Daily Allowance (RDA) of 60 mg/day should be advised (Makoff, 1999). I.v. ascorbic acid should be considered as a possible adjuvant to therapy in patients who are "iron-overloaded" and hyporesponsive to Epoetin alfa. Although the long-term effects of i.v. ascorbic acid on HD patients is unknown, the potential risk of secondary oxalosis should be considered (Costello, 1991; Pru, Eaton, & Kjellstrand, 1985). It may be necessary to monitor plasma oxalate levels if long-term therapy with i.v. ascorbic acid is used. Clinical studies have examined i.v. ascorbic acid doses from 300 mg-500 mg given up to TIW for a maximum duration of 12 weeks without any significant deleterious effects (Gastaldello et al., 1995; Tarng & Huang, 1998; Tarng et al., 1999). However, large-scale, prospective, and controlled trails are needed to determine the long-term safety and efficacy of i.v. ascorbic acid therapy in iron overloaded HD patients receiving Epoetin alfa.
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PMID:Ascorbic acid use in hyporesponders to Epoetin alfa. 1127 34

Osteoporosis and femoral neck fractures (FNF) are uncommon in black Africans although osteoporosis accompanying iron overload (from traditional beer brewed in iron containers) associated with ascorbic acid deficiency (oxidative catabolism by iron) has been described from sub-Saharan Africa. This study describes histomorphometric findings of iliac crest bone biopsies and serum biochemical markers of iron overload and of alcohol abuse and ascorbic acid levels in 50 black patients with FNFs (29 M, 21 F), age 62 years (40-95) years (median [min-max]), and in age- and gender-matched black controls. We found evidence of iron overload in 88% of patients and elevated markers of alcohol abuse in 72%. Significant correlations between markers of iron overload and of alcohol abuse reflect a close association between the two toxins. Patients had higher levels of iron markers, i.e., siderin deposits in bone marrow (P < 0.0001), chemical non-heme bone iron (P = 0.012), and serum ferritin (P = 0.017) than controls did. Leukocyte ascorbic acid levels were lower (P = 0.0008) than in controls. The alcohol marker mean red blood cell volume was elevated (P = 0.002) but not liver enzymes or uric acid. Bone volume, trabecular thickness, and trabecular number were lower, and trabecular separation was greater in patients than in controls, all at P < 0.0005; volume, surface, and thickness of osteoid were lower and eroded surface was greater, all at P < 0.0001. There was no osteomalacia. Ascorbic acid deficiency accounted significantly for decrease in bone volume and trabecular number, and increase in trabecular separation, osteoid surface, and eroded surface; iron overload accounted for a reduction in mineral apposition rate. Alcohol markers correlated negatively with osteoblast surface and positively with eroded surface. Relative to reported data in white FNF patients, the osteoporosis was more severe, showed lower osteoid variables and greater eroded surface; FNFs occurred 12 years earlier and were more common among men. We conclude that the osteoporosis underlying FNFs in black Africans is severe, with marked uncoupling of resorption and formation in favor of resorption. All three factors--ascorbic acid deficiency, iron overload, and alcohol abuse--contributed to the osteoporosis, in that order.
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PMID:Ascorbic acid deficiency, iron overload and alcohol abuse underlie the severe osteoporosis in black African patients with hip fractures--a bone histomorphometric study. 1554 37

One tablet of Sorbifer Durules contains 100 mg Fe2+ and 60 mg vitamin C. The authors examined in a short-term study 24 haemodialyzed patients with chronic renal failure of different etiology. The investigation was divided into three parts. During the first 4 weeks the patients did not receive Fe2+ nor vitamin C. During the subsequent four weeks the patients had Sorbifer Durules, one tablet/24 hours. This period was followed by another four weeks when the patients went again without Fe2+ and vitamin C treatment. At regular intervals, i.e. on days 0, 28, 56 and 84 the authors assessed the packed cell volume, blood haemoglobin and serum iron level, the total iron binding capacity, transferrin saturation, ferritin, and vitamin C in serum as well as the plasma oxalic acid level. Four weeks treatment using Sorbifer Durules led to a significant rise of the packed cell volume and haemoglobin in blood, iron and vitamin C in serum. This treatment did not affect the oxalic acid plasma level. Oral treatment with Sorbifer Durules, one tablet/24 hours, was adequate for maintaining the serum iron concentration in haemodialyzed patients during treatment with recombinant human erythropoietin. This treatment prevented at the same time the development of vitamin C deficiency in serum and a further rise of plasma oxalic acid in these patients.
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PMID:[Oral administration of iron with vitamin C in haemodialyzed patients]. 1563 85

We report a 10-month-old boy with inflammatory and necrotic gingival lesions, fever, irritability, and pseudoparalysis of the legs. Laboratory examinations revealed moderate anemia and skeletal X-rays showed osteopenia, scorbutic rosary at the costochondral junctions, and "corner sign" on the proximal metaphyses of the femora. The boy had been fed only with diluted cow's milk. He had never taken solid food, vitamin C, or iron complement. Seventy-two hours after starting oral vitamin C supplementation, there was significant improvement in the patient's gingival lesions and general health. The clinical presentation and laboratory and imaging findings, together with the dramatic response to ascorbic acid intake, allowed us to confirm the diagnosis of infantile scurvy. Scurvy, a dietary disease due to the deficient intake of vitamin C, is uncommon in the pediatric population. In an infant who has never received vitamin C, the combination of gingival lesions, pseudoparalysis, and irritability strongly suggests a diagnosis of scurvy. The clinical picture, together with the laboratory data, radiological studies, and therapeutic response to vitamin C administration, confirmed the diagnosis.
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PMID:Scurvy in a 10-month-old boy. 1726 76

Ascorbic acid (vitamin C) is necessary for the formation of collagen, reducing free radicals, and aiding in iron absorption. Scurvy, a disease of dietary ascorbic acid deficiency, is uncommon today. Indeed, implementation of dietary recommendations largely eradicated infantile scurvy in the US in the early 1900s. We present a case of an otherwise healthy 2-year-old Caucasian girl who presented with refusal to walk secondary to pain in her lower extremities, generalized irritability, sleep disturbance, and malaise. The girl's parents described feeding the patient an organic diet recommended by the Church of Scientology that included a boiled mixture of organic whole milk, barley, and corn syrup devoid of fruits and vegetables. Physical examination revealed pale, bloated skin with edematous, violaceous gums and loosening of a few of her teeth. Dermatologic findings included xerosis, multiple scattered ecchymoses of the extremities, and perifollicular hemorrhage. Laboratory and radiographic evaluation confirmed the diagnosis of scurvy. The patient showed dramatic improvement after only 3 days of treatment with oral ascorbic acid and significant dietary modification. In this case report, we revisit the old diagnosis of scurvy with a modern dietary twist secondary to religious practices. This case highlights the importance of taking a detailed dietary history when evaluating diseases involving the skin.
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PMID:Infantile scurvy: an old diagnosis revisited with a modern dietary twist. 1742 15

Background. Ascorbic acid (vitamin C) is necessary for the formation of collagen, reducing free radicals, and aiding in iron absorption. SCURVY, a disease of dietary ascorbic acid deficiency, is uncommon today. It still exists in high risk groups including economically disadvantaged populations with poor nutrition. The incidence of SCURVY in the pediatric population is very low. Cases Report. Here we report two cases of SCURVY revealed by subperiosteal hematoma in children with cerebral palsy and developmental delay. Conclusion. SCURVY is extremely rare in children. Musculoskeletal manifestations are prominent in pediatric SCURVY. Multiple subperiosteal hematomas are an important indicator for diagnosis.
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PMID:Infantile scurvy: two case reports. 2097 62


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