ascorbic-acid and Siderosis

Topics: Adult; Ascorbic Acid; Clinical Trials as Topic; Humans; Iron; Male; Oxalates; Oxidation-Reduction; Scurvy; Siderosis; South Africa

Topics: Ascorbic Acid; Folic Acid; Humans; Magnetic Resonance Imaging; Phenylketonurias; Siderosis

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.

Topics: Adult; Aged; Aged, 80 and over; Alcoholism; Ascorbic Acid; Ascorbic Acid Deficiency; Biomarkers; Black People; Bone Marrow; Female; Femoral Neck Fractures; Humans; Ilium; Iron Overload; Leukocytes; Male; Middle Aged; Osteoporosis; Siderosis

Ascorbic acid (AA) metabolism was studied in control and iron-loaded guinea pigs. All animals were fed an AA-deficient diet and given a daily intraperitoneal (ip) dose of 10 mg sodium ascorbate. The control-diet formula contained 0.10 g Fe/kg diet; the experimental diet contained an additional 3.33 g Fe/kg diet as FeSO4. After 14 wk animals were injected (ip) with 9.25 x 10(3) Bq [1-14C]L-ascorbic acid. Blood was collected for 10 d and plasma specific activity of AA was determined. All animals were subsequently killed and selected tissues were analyzed for AA and iron concentrations. In spite of marked elevation of iron concentrations in plasma, spleen, and liver in experimental animals compared with controls, no differences in AA metabolism as determined by tissue AA concentrations and AA half-life, turnover rate, and body-pool size were evident. These results demonstrate that iron loading has no effect on the rate of AA catabolism in guinea pigs.

Topics: Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Diet; Guinea Pigs; Half-Life; Iron; Liver; Male; Models, Biological; Siderosis; Spleen

Siderosis of rabbit articular chondrocytes was produced in vitro as a model for the cartilage damage of hemophilic arthropathy. Both FeSO4 0.1-2.5 mM and rabbit hemoglobin (as hemolyzed serum, 14 mg/ml) caused iron storage in cell and organ culture. FeSO4 was far more effective. The fine structure of the siderosomes resulting from both iron sources was comparable to that observed in hemophilic and other forms of hemosiderosis. Particles resembling ferric oxyhydroxide were included in the FeSO4 but not the hemoglobin derived siderin. Iron storage following FeSO4 was enhanced 5-fold by culturing with rabbit rather than fetal calf serum. Despite repeated washing of the cultures and detachment with trypsin, an extracellular pool of Fe3+ persisted in the cell pellets. Cytotoxicity of Fe was manifested by formation of myelin bodies and a dose-dependent reduction of cell number. There was an inverse relationship between cytotoxicity and iron storage following administration of FeSO4 to five other cell types. Ascorbate 40 micrograms/ml stimulated DNA synthesis but had no protective effect against the cytotoxicity of FeSO4. Little erythrophagocytosis was showen by the chondrocytes. Desferrioxamine (0.01--2.5 mM) was markedly toxic for dividing but not for stationary chondrocytes. Administered after iron storage had been induced with FeSO4, 1.0--2.5 mM desferrioxamine removed stainable siderin granules over the course of 4 days.

Topics: Animals; Ascorbic Acid; Cartilage, Articular; Cattle; Cells, Cultured; Deferoxamine; Disease Models, Animal; Erythrocytes; Ferrous Compounds; Iron; Organ Culture Techniques; Phagocytes; Rabbits; Siderosis

Topics: Adolescent; Adult; Ascorbic Acid; Deferoxamine; Drug Synergism; Humans; Siderosis

Since deferoxamine B, when administered as a single daily intramuscular injection of 0.75 g, is unable to promote sufficient urinary iron excretion to achieve net negative iron balance in siderosis, we evaluated its administration as a constant infusion over 24 hours. We compared intravenous and subcutaneous routes in 24 siderotic patients who had excreted 420 to 630 mg (mean, 480 mg) of iron per month on intramuscular therapy. With the intravenous route urinary iron excretions increased to 570 to 3690 mg (mean, 1595 mg) per month. Constant subcutaneous delivery was 90 per cent as effective as intravenous administration on a dose-for-dose basis. Noteworthy net cumulative urinary iron excretions (urinary iron excretions minus transfused iron), often in excess of 1 g per month, have been maintained in all patients. Constant subcutaneous deferoxamine administration may prove to be an effective and practical means of eliminating large quantities of iron in siderosis.

Topics: Administration, Oral; Adolescent; Adult; Aged; Ascorbic Acid; Child; Child, Preschool; Deferoxamine; Humans; Injections, Intramuscular; Injections, Subcutaneous; Iron; Middle Aged; Siderosis; Thalassemia; Time Factors

Topics: Adult; Ascorbic Acid; Humans; Liver; Male; Middle Aged; Siderosis; Silicotuberculosis

Topics: Adult; Age Factors; Animals; Ascorbic Acid; Ascorbic Acid Deficiency; Black or African American; Black People; Bone and Bones; Bone Resorption; Humans; Iron; Liver; Male; Middle Aged; Minerals; Osteoporosis; Siderosis; South Africa

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Black or African American; Bone Marrow; Humans; Iron; Leukocytes; Siderosis

Topics: Ascorbic Acid; Ascorbic Acid Deficiency; Deferoxamine; Hemochromatosis; Humans; Iron; Leukocytes; Male; Siderosis; Transfusion Reaction

Studies of the ascorbic acid status in two subjects with idiopathic haemochromatosis and in 12 with transfusional siderosis showed that all had decreased levels of white cell ascorbic acid. The urinary excretion of ascorbic acid was also diminished in those subjects in whom such measurements were made. The administration of ascorbic acid was followed by only a small rise in the urinary ascorbic acid output, while the oxalic acid levels (measured in two subjects) showed a significant rise. These findings resemble those described in siderotic Bantu, and support the thesis that increased iron stores lead to irreversible oxidation of some of the available ascorbic acid.

Topics: Adolescent; Adult; Ascorbic Acid; Blood Platelets; Blood Transfusion; Child; Diet; Hemochromatosis; Humans; Iron; Leukocytes; Middle Aged; Oxalates; Siderosis; Thalassemia

Topics: Adult; Ascorbic Acid; Ascorbic Acid Deficiency; Beer; Black or African American; Black People; Diet; Humans; Iron; Male; Middle Aged; Osteoporosis; Siderosis; South Africa