Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Because peroxidative damage to red cell membranes may contribute to the pathophysiology of sickle cell disease, deficiency of fat- and water-soluble antioxidants could be a determinant in the pathogenesis of this disease. We have previously reported a deficiency of vitamin E in sickle cell disease. The present study was undertaken to see if a deficiency in vitamin C might also be detected. Leukocyte vitamin C, which reflects total body vitamin C reserve, was measured by a modified 2,4-dinitrophenylhydrazine method. Sickle cell patients (N = 18) had lower leukocyte vitamin C levels (18.3 +/- 9.4 micrograms/10(8) cells) than normal controls (N = 12; 30.3 +/- 7.5 micrograms/10(8) cells; p less than 0.01). Furthermore, 50% of the patients had vitamin C levels below 15 micrograms/10(8) cells, a value consistent with vitamin C deficiency. A statistically significant correlation (r = -0.62 with 0.01 less than p less than or equal to 0.025) was found between leukocyte vitamin C levels and serum ferritin concentration. Because dietary vitamin C intake appeared to be adequate, increased vitamin C utilization may account for this deficiency. However, the mechanisms for this deficiency as well as its pathophysiologic consequences remain to be established.
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PMID:Vitamin C deficiency in patients with sickle cell anemia. 224 Apr 72

Two physicochemically and metabolically separate pools of ferritin, namely cytosolic ferritin and lipid-associated ferritin, are present in the livers of guinea pigs. In this paper we establish that the iron content of cytosolic ferritin is dependent on and linearly related to ascorbic acid concentration, whereas changes in concentration of this vitamin do not affect the iron content of lipid-associated ferritin. In livers of ascorbic acid-deficient guinea pigs both synthesis and degradation of cytosolic ferritin are diminished equally. Consequently cytosolic ferritin is metabolized more slowly without changes in its pool size. In contrast with cytosolic ferritin, the metabolism of lipid-associated ferritin is unaffected by ascorbic acid deficiency. The differential effects of ascorbic acid deficiency on the physicochemical characteristics as well as on the metabolism of cytosolic ferritin and lipid-associated ferritin suggest that the two forms of ferritin have different functional roles.
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PMID:Ascorbic acid deficiency affects the metabolism of cytosolic ferritin but not lipid-associated ferritin in livers of guinea pigs. 233 6

When highly purified hepatic 59Fe-ferritin was injected intravenously into normal guinea-pigs more than half of it was taken up by red cell precursors and the iron was used for haem formation. This was studied in more detail in animals in which a reticulocytosis had been induced either by phenylhydrazine or by repeated venescetions. 55% of the injected ferritin iron was found in reticulocytes at 1 h. Experiments using ferritin doubly labelled with 59Fe and 125I indicated that the whole molecule was taken up, with two-thirds of the radioactivity being associated with the membrane at 1 h and one third being already within the cell. There was a progressive loss of 125I activity over the ensuing hours, while most of the 59Fe was slowly internalized and incorporated into haem between 1 and 24 h. In contrast, 90% of the activity taken up by red cell precursors from 59Fe-transferrin was present as haem at all times. The liver and spleen were the two other major sites of 59Fe-ferritin uptake in phenylhydrazine treated animals. While there was an early uptake of 59Fe into haem in these organs, some redistribution occurred with time, since most of the 59Fe was in a non-haem fraction by 24 h. In a final experiment the distribution and fate of 59Fe-ferritin was studied in scorbutic animals treated with phenylhydrazine. The findings were similar to those in normals similarly treated, which suggests that ferritin iron was being effectively mobilized for haem formation despite the ascorbic acid depletion.
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PMID:The fate of intravenously administered hepatic ferritin in normal, phenylhydrazine-treated and scorbutic guinea-pigs. 382 33

Tissue ferritin metabolism was compared in control and ascorbic acid (AA) deficient guinea-pigs. Concentrations of ferritin protein in the liver (0.98 +/- 0.61 mg/g wet weight) and spleen (0.48 +/- 0.23 mg/g) of control animals did not change after tissue depletion of AA. Iron dextran (75 mg/kg weight, i.m.) caused a 4-5-fold increase in tissue ferritin concentrations in controls whereas no increase in tissue ferritin occurred in scorbutic animals. The rise in tissue total iron concentration was similar in the two groups. Liver ferritin synthesis was similar in control and scorbutic animals. After stimulation with iron (8 mg/kg iron dextran i.v.), ferritin synthesis rose in both groups of animals. However, the pattern of response differed. At 24 h after iron dextran, ferritin synthesis in controls was still significantly elevated (P less than 0.001) and liver ferritin protein continued to rise, whereas in scorbutic animals, ferritin synthesis had declined to pre-iron injection levels, and no rise in ferritin protein values occurred. It is concluded that the ferritin synthetic apparatus in AA deficient tissues remained intact and capable of responding to added iron. The absence of a sustained elevation in tissue ferritin protein after an iron load appeared to be due to inadequate stimulation of ferritin synthesis by intracellular iron. It is suggested that AA has a physiological role in the reduction of intracellular iron and that it is the reduced form of iron which stimulates ferritin synthesis. Abnormalities of iron metabolism occur in AA depleted tissues when the quantity of Fe3+ entering cells exceeds the residual reducing capacity of those cells.
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PMID:Tissue ferritin in scorbutic guinea-pigs. 661 28

Liver and spleen iron concentrations, serum ferritin level and binding of S-ferritin to concanavalin A (Con A) were measured in 12 patients with thalassaemia major or intermedia at the time of splenectomy. All these subjects had increased liver iron concentration, most of them had hepatic fibrosis but none of them had histological evidence of chronic hepatitis. No patient had ascorbic acid deficiency. Serum ferritin concentration was increased in all cases, ranging from 266 to 5504 micrograms/l. In all but 2 subjects most of the protein did not bind to Con A, thus behaving as tissue ferritin. There were highly significant correlations between serum ferritin concentration, amount of blood transfused and liver iron concentration. On the average, iron concentration in the liver was about 3 times that in the spleen. The findings obtained suggest that in patients with thalassaemia major or intermedia most of the iron is deposited in parenchymal tissues and most of the S-ferritin derives by leakage from the cytosol of iron-loaded parenchymal cells. S-ferritin is a valid index of liver iron overload in thalassaemic patients without complications such as viral hepatitis and/or ascorbic acid deficiency.
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PMID:Internal distribution of excess iron and sources of serum ferritin in patients with thalassemia. 685 45

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

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

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

The prevalence of oral candidiasis and its association with malnutrition in terms of protein-energy malnutrition and mineral and vitamin depletion were evaluated in ninety-seven hospitalised older adults aged 82.1 (SD 8.6) years. Patients underwent a complete oral examination with microbiological investigation on admission to our geriatric rehabilitation unit. Patients were assessed nutritionally by evaluation of dietary intake and measurement of anthropometric variables, serum nutritional proteins, ferritin, Zn, folate, vitamins B12 and C. The prevalence of oral candidiasis was 37% (n 36); the proportion of patients with BMI <20 kg/m(2) was 32% (n 31). The nutritional status of the population was studied by comparing two groups defined according to the absence (group I; n 61) or presence (group II; n 36) of oral candidiasis. The two groups did not differ on the basis of BMI and mid-arm circumference. However, group II had a smaller leg circumference, lower daily energy and protein intakes, lower albumin and transthyretin levels. Patients successfully treated with fluconazole increased their intake on day 30. The proportion of patients with hypozincaemia (<12.5 micromol/l) and vitamin C deficiency (<0.7 mg/l) was higher in group II. Treatment with antibiotics, poor oral hygiene, denture wearing, and vitamin C deficiency appeared as the most significant independent risk factors associated with oral candidiasis. The present findings show that oral candidiasis appears to be related to malnutrition and results in mucosal lesions that have a negative impact on energy intake, which may subsequently worsen nutritional status.
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PMID:Oral candidiasis and nutritional deficiencies in elderly hospitalised patients. 1553 76

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


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