ascorbic-acid and Hemosiderosis

Parenteral ascorbic acid has been frequently used to overcome problems of vitamin C deficiency in haemodialysis patients. The benefits of vitamin C supplementation in clinical studies have been controversial and did not consider toxicological aspects. The review summarizes recent findings of the effects of parenteral ascorbic acid and discusses toxicological effects.. Vitamin C deficiency in haemodialysis patients, which has been frequently described, cannot be improved with oral supplementation due to limited absorption of high dosages. To avoid consequences of vitamin C deficiency, parenteral vitamin C solutions should be administered because this intervention is the only way to guarantee a sufficient supply to the cells. A beneficial consequence of parenteral vitamin C on the recombinant human erythropoietin resistance is an additional therapeutic effect, which contributes to the prevention of iron deficiency anaemia in haemodialysis patients. Thus, large amount of supplemental vitamin C are required for extended periods of time (up to 500 mg 3 times a week). To avoid hyperoxaluria, plasma oxalate levels should be monitored on a regular basis, for example, once a week.. Parenteral administration of ascorbic acid may be an approach that can overcome problems of vitamin C deficiency in haemodialysis patients - in particular problems of iron overload, erythropoetin resistance, and chronic inflammation.

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Drug Resistance; Erythropoietin; Hemosiderosis; Humans; Inflammation; Infusions, Parenteral; Renal Dialysis

Topics: Adolescent; Adult; Ascorbic Acid; Blood Transfusion; Cardiomyopathies; Deferoxamine; Dose-Response Relationship, Drug; Ferritins; Growth Disorders; Heart Diseases; Hemosiderosis; Humans; Iron; Iron Chelating Agents; Liver; Liver Diseases; Pancreatic Diseases; Parathyroid Diseases; Pituitary Diseases; Thyroid Function Tests

Haemosiderosis is the most common cause of death in patients with thalassaemia major because of haemolysis and the necessary repeated transfusions. It is possible to reduce the lethal iron burden by means of iron-chelating agents. We combine a two-day-high-transfusion-regimen of packed cells with the application of high doses of desferrioxamine (500 mg/kg body weight) intravenously. This way we achieve good iron elimination with minimal psychological stress situations.

Topics: Ascorbic Acid; Blood Transfusion; Child; Deferoxamine; Female; Germany, West; Greece; Hemosiderosis; Humans; Male; Thalassemia; Trace Elements; Turkey

Topics: Ascorbic Acid; Blood Transfusion; Chelating Agents; Deferoxamine; Diet; Gentisates; Hemochromatosis; Hemosiderosis; Hydroxamic Acids; Hydroxybenzoates; Iron; Piperazines; Syndrome

Haemodialysis patients with iron overload sometimes develop resistance to erythropoietin therapy due to 'functional iron deficiency'. It is known that this resistance may be overcome by iron supplementation; however, the latter could worsen haemosiderosis. Therefore, we treated four iron-overloaded haemodialysis patients who had developed relative resistance to erythropoietin (among whom three had features of 'functional iron deficiency') with ascorbic acid (500 mg intravenously after haemodialysis, 1-3 times a week). The erythropoietin doses were voluntarily kept unchanged during the study. After a latency of 2-4 weeks, haematocrit and haemoglobin had increased respectively from 26.5 +/- 0.7 to 32.7 +/- 0.4 vol% and from 8.8 +/- 0.3 to 10.8 +/- 0.2 g/dl (means +/- SEM, P < 0.001). While serum ferritin remained unchanged, transferrin saturation increased from 27 +/- 7 to 54 +/- 12% (P < 0.05), suggesting that ascorbic acid supplementation had allowed mobilization of iron from tissue burdens. In one patient, haematocrit declined after withdrawal of vitamin C and increased again after rechallenge. Also, ascorbate supplementation was continued after the study in two patients and allowed the erythropoietin doses to be decreased, 8 and 11 weeks, respectively, after the start of the trial. When a control group of seven patients with normal iron status and without resistance to erythropoietin were challenged in the same manner with ascorbate, no elevation of haematocrit or transferrin saturation was noted. We conclude that ascorbate supplementation may circumvent resistance to erythropoietin that sometimes occurs in iron-overloaded patients, in particular, in the setting of 'functional iron deficiency'.

Topics: Adult; Ascorbic Acid; Drug Resistance; Erythropoietin; Hematocrit; Hemoglobins; Hemosiderosis; Humans; Iron Deficiencies; Middle Aged; Renal Dialysis

The aim of this study was to optimize reverse iontophoretic (RI) extraction of ferric/ferrous ions from the cornea.. Group I consisted of the right eye corneas from 20 normal rabbits. Corneal blood staining was induced in 60 right eyes. The corneal depths from the endothelium to the epithelium layers were divided into three groups by slit-lamp examination: Group II, one-third corneal thickness; Group III, one-half corneal thickness; Group IV, full corneal thickness. RI was performed using vertical diffusion cells. The lower chamber was loaded with glutathione bicarbonate Ringer's buffer (GBR; pH 7.0) or vitamin C (12.5 mg/mL) and GBR (pH 7.0), while the upper chamber was filled with 1 mL GBR. Progress of corneal blood staining removal was evaluated.. Application of 1.5 mA to the cornea increased flux by 1.72- and 2.19-fold in Groups III and IV, respectively, but not in Groups I or II, compared to the control. When vitamin C was included, we observed significant flux increases in the controls (1.5-, 2.06-, 2.60-, and 4.59-fold) for Groups I, II, III, and IV, and under RI conditions for Groups III and IV. Following RI, the corneal endothelia appeared similar to corneas from untreated control rabbits, while Draize scores were zero.. These results suggested that extracellular ferric/ferrous ions could be extracted from the cornea in vitro by RI, and that vitamin C reduced Fe(3+) to Fe(2+) in the cornea and altered its permselectivity, thus increasing the RI contribution to iron extraction.

Topics: Animals; Antioxidants; Ascorbic Acid; Cornea; Corneal Diseases; Disease Models, Animal; Female; Hemosiderosis; Iontophoresis; Iron Compounds; Male; Rabbits; Spectrophotometry, Atomic

Topics: Aging; Ascorbic Acid; Beverages; Bone Diseases; Citrates; Citric Acid; Diabetes Mellitus; Drug Synergism; Fruit; Hemosiderosis; Humans; Iron; Neoplasms; Oxidative Stress

This paper aims to examine the relative contributions made by alcohol and iron overload and hypovitaminosis C to the osteoporosis associated with African hemosiderosis. To characterize this bone disorder, we examined double-tetracycline-labeled iliac crest bone biopsies and serum biochemistry in 53 black male drinkers, 38 with (Fe+) and 15 without (Fe-) iron overload, and in controls. We reasoned that abnormalities found in both patient groups were likely to be caused by alcohol abuse and those found only in the Fe+ group to be caused by iron overload and hypovitaminosis C (iron/C-). The patient groups differed only with respect to greater erosion depth (p < 0.05) and abnormal markers of iron overload in the Fe+ group. Ascorbic acid levels were lower in the Fe+ group than in controls (p < 0.001). Bone volume and trabecular thickness were significantly lower in both patient groups compared with controls and therefore likely caused by alcohol. There were no positive correlations between formation and erosion variables in either patient group, which suggests uncoupling of formation from erosion, possibly as a result of alcohol abuse. Prolonged mineralization lag time associated with thin osteoid seams was found in 32% of patients, affecting both groups. This rules out osteomalacia and suggests osteoblast dysfunction, probably caused by alcohol. The number of iron granules in the marrow correlated with erosion depth (r = 0.373, p < 0.01), trabecular number (r = -0.295, p < 0.05), and trabecular separation (r = 0.347, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Africa; Aged; Alcoholism; Ascorbic Acid; Bone Density; Hemosiderosis; Humans; Ilium; Iron; Male; Middle Aged; Osteoporosis; Primary Myelofibrosis

Topics: Adult; Ascorbic Acid; Deferoxamine; Dose-Response Relationship, Drug; Feces; Hemosiderosis; Humans; Intestinal Absorption; Iron; Thalassemia; Transfusion Reaction

Chronic refractory anemia associated with congenital hypoplastic anemia (CHA, Blackfan-Diamond syndrome) and with the 5q-syndrome may require chronic transfusion therapy to sustain life. Hemosiderosis and death from chronic iron overload may result from such a program. The effect of subcutaneous (SC) deferoxamine (DF) and supplemental oral vitamin C (vit. C) on urinary iron excretion was studied in two patients with congenital hypoplastic anemia and one patient with 5q-syndrome. In the two patients with CHA, urinary iron excretion in response to DF given SC over 24 hours was comparable to the results following intravenous (I.V.) administration. Both of these cases had low levels of plasma ascorbate on initial evaluation and excreted more iron in response to two different doses of DF after they had received supplemental vit C and their stores were repleted. Significant iron excretion occurred in all three patients for 12 hours during the SC infusion of DF and for 12 hours after the end of the infusion. In all three patients, increasing the dose of DF up to 3-4 g given SC over 12 hours resulted in a linear increase in iron excretion. Once normal body stores of ascorbate were achieved by oral supplementation, increasing doses of vit C did not appear to cause a further increment in iron excretion. DF administered by a slow SC infusion appears to be an effective approach to iron overload in patients with refractory anemia and hemosiderosis secondary to chronic transfusions. Only small amounts of supplemental vit. C necessary to sustain adequate body stores are required for optimal iron excretion.

Topics: Administration, Oral; Anemia, Aplastic; Ascorbic Acid; Blood Transfusion; Child; Chromosome Aberrations; Chromosome Disorders; Chromosomes, Human, 4-5; Deferoxamine; Female; Hemosiderosis; Humans; Injections, Subcutaneous; Iron; Male; Middle Aged; Syndrome

Topics: Administration, Oral; Adult; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Deferoxamine; Female; Guinea Pigs; Hemosiderosis; Humans; Injections, Subcutaneous; Iron; Male; Scurvy; Thalassemia; Transfusion Reaction

Topics: Adolescent; Adult; Aged; Ascorbic Acid; Deferoxamine; Drug Evaluation; Female; Hemochromatosis; Hemosiderosis; Humans; Iron; Male; Middle Aged; Thalassemia

Topics: Anemia, Sideroblastic; Animals; Ascorbic Acid; Chelating Agents; Deferoxamine; Hemosiderosis; Humans; Iron; Metabolic Diseases; Thalassemia

The effect of 12 and 24 h continuous subcutaneous infusion of desferrioxamine (D.F.) on urinary iron excretion was compared in 13 patients with beta-thalassaemia major and 1 with congenital sideroblastic anaemia, all of whom were receiving regular blood-transfusions. 750 mg D.F. given over a 12 h period, gave a mean total (30 h) iron excretion of 17-5 mg, which was not statistically different from the mean iron excretion of 21-5 mg when the same dose was delivered over 24 h. 1500 mg D.F. gave a mean urinary iron excretion of 28-1 mg with a 12 h infusion, which was significantly less than the mean iron excretion of 39-6 mg with 24 h infusion. The 1500 mg dose gave a significant increase in iron excretion compared with the 750 mg dose when given by either 12 h or 24 h infusion. 7 of 8 patients, given D.F. over a 12 h period, had increased iron excretion when the dose was increased from 750 to 2000 mg. When the dose was increased to 4000 mg, however, the effect on iron excretion was variable. On the other hand, ascorbic-acid therapy was invariably associated with increased iron excretion after subcutaneous D.F. In twelve studies at different dose levels of D.F., ascorbate therapy was associated with increased iron excretion ranging from 24 to 245%. It is concluded that in most patients with transfusional iron overload subcutaneous D.F over a 12 h period, at a dose ranging from 2 to 4 g daily with ascorbic-acid saturation, is at present the most satisfactory method of removing excess iron.

Topics: Administration, Oral; Adolescent; Adult; Anemia, Sideroblastic; Ascorbic Acid; Child; Deferoxamine; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Female; Hemosiderosis; Humans; Infusions, Parenteral; Iron; Male; Skin; Thalassemia; Transfusion Reaction

Adult patients with transfusional hemosiderosis were given ascorbic acid and treated with the iron chelator, desferrioxamine B. The drug was administered by continuous subcutaneous or intravenous infusions using a light weight portable constant infusion device. On this regimen, four of the five patients studied were able to excrete significant amounts of iron (greater than 35 mg/da) when receiving a daily desferrioxamine dose of 1.5 to 2.2 g. Continuous subcutaneous infusion was well tolerated and about 80 per cent as effective as intravenous therapy in chelating iron. The number of prior transfusions, the hepatic iron content and the serum ferritin levels appear to be useful in predicting which patients will respond to iron chelation therapy, especially if there is little bone marrow erythropoietic activity. One patient with ineffective erythropoiesis did not have significantly increased hepatic iron stores but responded to the administration of desferrioxamine. Continuous subcutaneously administered desferrioxamine may prove to be adaptable for long-term outpatient therapy, allowing patients with ongoing transfusion requirements to go into negative iron balance. Long-term studies will be needed to demonstrate reversal of endocrine, hepatic and cardiac dysfunction secondary to iron deposition in these patients.

Topics: Adult; Aged; Ascorbic Acid; Biopsy, Needle; Deferoxamine; Female; Ferritins; Hemosiderosis; Humans; Infusions, Parenteral; Iron; Liver; Liver Cirrhosis; Male; Middle Aged; Primary Myelofibrosis; Transfusion Reaction

Topics: Adult; Anemia, Sideroblastic; Ascorbic Acid; Deferoxamine; Drug Administration Schedule; Female; Hemosiderosis; Humans; Injections, Intravenous; Injections, Subcutaneous; Iron; Male; Middle Aged; Primary Myelofibrosis; Thalassemia; Transfusion Reaction

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Black People; Child; Disease Models, Animal; Guinea Pigs; Hemosiderosis; Humans; Iron; Leukocytes; Liver; Oxalates; South Africa; Thalassemia

South African Bantu patients with a scurvy-type skin, which developed after a prolonged, iron-induced hemosiderosis, were studied with ascorbic acid-1-C14 and the 2 gm tryptophan load test. The metabolism of the two compounds was found to be abnormal in these patients. The data suggested that ascorbic acid was rapidly (iron accelerated) metabolized to monodehydroascorbate, a compound that rapidly reacts with tissue DPNH to form DPN. This mechanism could reduce tissue levels of DPNH such that the feed-back control of tryptophan pyrolase enzyme was depressed. The change in control level of the pyrrolase enzyme permitted large quantities of tryptophan to be converted into the kynurenine pathway products, and a smaller quantity for the serotonin pathway. This mechanism could contribute to the abnormal tryptophan metabolism found in chronic pellagrins with dementia.

Topics: Ascorbic Acid; Female; Hemosiderosis; Humans; Iron; Male; Middle Aged; Scurvy; Tryptophan

Topics: Adult; Ascorbic Acid; Black People; Carbon Dioxide; Carbon Radioisotopes; Chromatography, Paper; Hemosiderosis; Humans; Male; Middle Aged; Oxalates; Scurvy; South Africa; Time Factors

Topics: Africa; Ascorbic Acid; Black People; Ethnicity; Female; Hemosiderosis; Humans; Male; Models, Chemical; Pellagra; Scurvy; Tryptophan

Topics: Adult; Ascorbic Acid; Blindness; Diabetes Complications; Female; Hemosiderosis; Humans; Male; Middle Aged; Oxalates; Retina; Retinal Detachment; Retinal Diseases

Topics: Arsenic; Ascorbic Acid; Diagnosis, Differential; Drug Therapy; Eczema; Egypt; Hemosiderosis; Histamine H1 Antagonists; Humans; Pathology; Pruritus; Purpura