Biomedical subjects

T H Bothwell

Publications and source records attributed to T H Bothwell.

At least 37 records · Page 2Linked to original sources

PubMed1990

Dietary iron overload in southern African rural blacks.

A survey conducted in rural southern African black subjects indicated that dietary iron overload remains a major health problem. A full blood count, erythrocyte sedimentation rate, serum concentrations of iron, total iron-binding capacity, ferritin, C-reactive protein (CRP), gamma-glutamyltransferase (GGT) and serological screening for hepatitis B and human immunodeficiency virus (HIV) infections were carried out in 370 subjects (214 inpatients and 156 ambulatory Mozambican refugees). The fact that the geometric mean (SD range) serum ferritin concentration was much higher in the male hospital patients than in subjects living in the community [1,581 micrograms/l (421-5,944 micrograms/l) and 448 micrograms/l (103-1,945 micrograms/l) respectively] suggested that dietary iron overload was not the only factor raising the serum ferritin concentration. The major additional factor appeared to be inflammation, since the geometric mean (SD range) serum CRP was significantly higher in male hospital patients [21 mg/l (8-53 mg/l)] than in subjects in the community [3 mg/l (1-5 mg)]. Alcohol ingestion, as judged by history and by serum GGT concentrations, was also associated with significantly raised serum ferritin concentrations. This finding was ascribed to the fact that traditional brews are not only associated with alcohol-induced hepatic damage but are also a very rich source of highly bio-available iron. The role of iron overload in the genesis of the raised serum ferritin concentrations are confirmed in the diagnostic liver biopsy study. The majority of biopsies showed heavy siderosis, with varying degrees of hepatic damage.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1990

Effect of traditional oriental soy products on iron absorption.

The effect of a variety of traditional oriental unfermented and fermented soy products on iron absorption was evaluated in 242 Indian women. When compared with a soy-flour meal containing an equal amount of protein, iron absorption was found to be significantly improved with silken tofu, natto, tempeh, rice miso, barley miso, and soybean miso. This improvement could not be adequately explained except with reference to changes in the protein composition of the products. The protein fraction profiles of the soy products were obtained by size-exclusion high-performance liquid chromatography. An inverse relationship between food iron absorption and the high-molecular-weight fraction of the soy products was demonstrated (r = 0.66, p = 0.01). However, anomalous results obtained with three products (sufu, tempeh, and fully hydrolyzed isolated soy protein) did not make it possible to reach firm conclusions concerning the effect of the protein fraction of soy on iron bioavailability.

Biological Availability↗

PubMed1990

Iron deficiency.

Explore the source record for details and available documents.

Anemia, Hypochromic↗

PubMed1990

Factors involved in the regulation of iron transport through reticuloendothelial cells.

The effects of various maneuvers on the handling of 59Fe-labeled heat-damaged red cells (59Fe HDRC) by the reticuloendothelial system were studied in rats. Raising the saturation of transferrin with oral carbonyl iron had little effect on splenic release of 59Fe but markedly inhibited hepatic release. Splenic 59Fe release was, however, inhibited by the prior administration of unlabeled HDRC or by the combination of carbonyl iron and unlabeled HDRC. When carbonyl iron was administered with unlabeled free hemoglobin, the pattern of 59Fe distribution was the same as that observed when carbonyl iron was given alone. 59Fe ferritin was identified in the serum after the administration of 59Fe HDRC but the size of the fraction was not affected by raising the saturation of transferrin. Sizing column analyses of tissue extracts from the spleen at various times after the administration of 59Fe HDRC revealed a progressive shift from hemoglobin to ferritin, with only small amounts present in a small molecular weight fraction. The small molecular weight fraction was greater in hepatic extracts, with the difference being marked in animals that had received prior carbonyl iron. The increased hepatic retention of 59Fe associated with a raised saturation of transferrin was reduced by a hydrophobic ferrous chelator (2,2'-bipyridine), a hydrophilic ferric chelator (desferrioxamine), and an extracellular hydrophilic ferric chelator (diethylene-triaminepentacetic acid). Transmembrane iron transport did not seem to be a rate-limiting factor in iron release, since no differences in 59Fe membrane fractions were noted in the different experimental settings. These findings are consistent with a model in which RE cells release iron from catabolized red cells at a relatively constant rate. When the saturation of transferrin is raised, a significant proportion of the iron is transported from the spleen to the liver either in small molecular weight complexes or in ferritin. Although a saturated transferrin had no effect on the release of iron from reticuloendothelial cells, prior loading with HDRC conditions them to release less iron.

2,2'-Dipyridyl↗

PubMed1990

The promotive effect of soy sauce on iron absorption in human subjects.

The effects on iron absorption of a traditionally fermented Japanese soy sauce added to soy and rice meals were assessed. The addition of soy sauce to a soy flour meal could not overcome the strong inhibition of iron absorption (geometric mean absorption 7.2 per cent with soy sauce vs. 8.7 per cent without, P = 0.5). However, soy sauce added to a rice meal instead of soy flour significantly improved the geometric mean iron absorption (13.9 per cent with soy sauce vs. 5.2 per cent with soy flour, P = 0.002) and had a promotory effect on absorption from a rice meal alone (11.4 per cent with soy sauce vs. 3.5 per cent without, P = 0.0002). Although soy sauce contains appreciable amounts of organic acids, the addition of 340 mg lactic acid to rice did not enhance iron absorption (3.1 per cent with lactic acid vs. 2.2 per cent without, P = 0.11). The promotory effect of soy sauce on iron absorption appears to be due not only to its lack of soy protein content but may also be due to the presence of fermentation products other than organic acids.

Biological Availability↗

PubMed1989

Iron metabolism in normal and hemochromatotic macrophages.

Certain metabolic pathways of iron were studied in macrophages (cultured human monocytes) obtained from normal and hemochromatotic subjects. The relative abilities of the hydrophobic ferrous chelator 2,2' bipyridine and the hydrophilic ferric chelators desferrioxamine (DFO) and diethylenetriaminepenta-acetic acid (DTPA) to release iron from normal and hemochromatotic macrophages which had previously been loaded with diferric transferrin were tested but there were no differences between the two groups. The relative affinity of the macrophages for diferric transferrin was next studied. Although the hemochromatic macrophages had a somewhat lower affinity for diferric transferrin iron than normal macrophages (Kd 4.7 x 10(-8) M vs. 3.0 x 10(-8)M) the difference did not reach statistical significance (t = 2.01013; P less than 0.07). In a further experiment there was no evidence that apotransferrin was directly involved in the release of iron from hemochromatotic macrophages. A clue to the nature of postendocytotic trans-membrane transport of iron was provided by the finding that it was inhibited by the hydrophobic ferrous chelator 2,2' bipyridine. However, the degree of inhibition was similar in both normal and hemochromatotic macrophages. In summary, none of the metabolic processes examined in the present study was abnormal in cultured human blood monocytes from hemochromatotic subjects.

Dose-Response Relationship, Drug↗

PubMed1989

Fortification of curry powder with NaFe(111)EDTA in an iron-deficient population: initial survey of iron status.

A survey of iron status was conducted in 984 volunteers (404 males and 580 females) from an Fe-deficient population before an Fe-fortification trial. Hemoglobin, percentage saturation of transferrin, and serum ferritin were used to assess Fe status and to calculate body Fe stores. Almost 30% of males and 60% of females had evidence of Fe deficiency. The distribution of body Fe stores for both males and females was shifted to the left compared with a population in the United States. In females 24% had Fe-deficiency anemia, 13% Fe-deficient erythropoiesis, and 16% depleted stores. Multiple regression analysis failed to show any relationship in women between age, parity, and duration of menses and measurements of Fe status. In males Fe deficiency was more frequent for those less than 18 y and alcohol abusers had increased serum ferritin and calculated body Fe compared with nondrinkers.

Adolescent↗

PubMed1989

Fortification of curry powder with NaFe(111)EDTA in an iron-deficient population: report of a controlled iron-fortification trial.

A targeted, double-blind controlled iron fortification trial using Fe(111)-EDTA in masala (curry powder) was directed towards an Fe-deficient Indian population for 2 y. The Fe status of the fortified group improved more than that of control subjects. Improvement reached significance over control subjects for females in hemoglobin (p = 0.0005), ferritin (p = 0.0002), and body Fe stores (p = 0.001) and for males in ferritin (p = 0.04). The prevalence of Fe-deficiency anemia (IDA) decreased from 22 to 5% in fortified females. Premenopausal women, multipara women, and women with prolonged menstruation or initial IDA benefitted most from fortification. The mean increase in body Fe stores in females with initial IDA was 9.0 +/- 1.3 mmol, representing an increased absorption of 12 mumol/d. Fortified subjects with normal Fe status did not accumulate excessive body Fe and there was no alteration in serum Zn concentrations. Targeted fortification is a safe and effective means of combatting Fe deficiency.

Adolescent↗

PubMed1989

Fortification of the diet as a strategy for preventing iron deficiency.

Progress in the fortification of food with iron is reviewed in the light of the different circumstances prevailing in the developed and developing world. Although fortification programmes are well established in developed countries many were not based on sound principles and there is no good evidence that they have proved effective. The important steps in establishing a fortification programme include accurate establishment of the need for iron fortification in a particular group or population, the choice of an appropriate combination of food vehicle and iron compound which is both stable and acceptable, and confirmation that the iron in the chosen blend is bioavailable and in different dietary settings. Only after the successful completion of controlled field trials using the chosen combination is the establishment of a regional or national fortification programme worthwhile. These points are illustrated by the success of field trials in the developing world, at least one of which has led to the implementation of a national programme directed to infants and children. Finally, a case study is described in which these principles were followed in the planning and execution of a successful field trial in an iron deficient Indian population in South Africa. The vehicle was curry powder and the iron compound Fe(111)EDTA.

Adolescent↗

PubMed1989

The fate of intravenously injected tissue ferritin in pregnant guinea-pigs.

The organ distribution of intravenously injected hepatic ferritin either labelled with 59Fe or with 59Fe and 125I, was studied in pregnant guinea-pigs. At 5 h 71.2% of injected 59Fe was present in the placenta and fetus. Transfer of 59Fe to the fetus was slow, with 11.2% present at 5 h and 38.6% at 21 h. Analysis of a placental cellular lysate for 59Fe and 125I revealed that the injected iron was present as intact ferritin at 2 h but by 21 h the ferritin had been catabolized, the 125I excreted and the 59Fe incorporated into endogenous ferritin. Most of the fetal 59Fe counts were detected in the liver, with 35.3% of the transferred 59Fe in ferritin, 30.4% in haemoglobin and 10.6% in a low molecular weight pool. The uptake of labelled ferritin by the placenta was inhibited by a 300-fold molar excess of unlabelled ferritin but not by albumin, asialofetuin or by the injection of carbon particles. A nonsignificant reduction in uptake was noted after injection of mannosylated bovine serum albumin. The mannosidase inhibitor swainsonine had no effect. Iron transfer to the fetus was not affected by various microtubular inhibitors. Presaturation of endogenous transferrin with oral carbonyl iron prevented iron release from the feto-placental unit back into the maternal circulation. In consequence, marrow 59Fe uptake by the maternal marrow was reduced. The ferrous chelator 2,2'-bipyridine significantly reduced 59Fe transfer to the fetus and this occurred irrespective of whether the chelator was given prior to or after 59Fe ferritin administration. The ferric chelator desferrioxamine had no such effect. Electron microscopy of placental tissues revealed endocytosis of ferritin molecules. These results indicate that the guinea-pig placenta takes up homologous tissue ferritin and transfers the iron slowly to the fetus after reductive mobilization. The process is compatible with a receptor-mediated pathway.

Animals↗

PubMed1989

Nutritional iron requirements and food iron absorption.

To prevent nutritional iron deficiency, sufficient iron must be absorbed from the diet to meet the normal physiological requirements. Daily iron losses in males are about 1 mg (14 micrograms kg-1), while the average additional requirements incurred in women include menstruation (0.6 mg), pregnancy (2.7 mg) and lactation (less than 0.3 mg). Requirements during pregnancy are not evenly distributed and increase to between 5-6 mg in the last trimester of pregnancy, which is more than can be absorbed from even an optimal diet. While the amounts absorbed are affected by the iron content of the diet, the composition of the latter is even more relevant. About one-quarter of the iron in haem proteins is absorbed regardless of the other components in the diet, while non-haem iron absorption is subject to the interplay of promoting and inhibiting substances in the diet. Thus diets rich in enhancers of non-haem iron absorption, chiefly meat and/or ascorbic acid, have high iron bioavailability (about 3 mg d-1) while diets in which inhibitors, such as polyphenols and phytates, predominate are poor sources of iron (less than 1 mg d-1). Examination of the relative proportions of promoters and inhibitors of iron absorption in individual foodstuffs and the measured iron absorption from them may be useful in predicting the overall iron bioavailability from mixed diets.

Anemia, Hypochromic↗

PubMed1989

A systematic evaluation of bathophenanthroline, ferrozine and ferene in an ICSH-based method for the measurement of serum iron.

The chromogenic substrates ferrozine and ferene were compared to bathophenanthroline disulphonic acid for the measurement of iron concentrations in aqueous and serum samples in an assay based on that of the Iron Panel of the International Committee for Standardisation in Haematology. Ferrozine and ferene were more sensitive than bathophenanthroline. Copper at physiological concentrations in plasma caused only minimal positive interference with all three chromogenic substrates when thioglycollic acid was used as the reducing agent, but when ascorbic acid was used significant positive interference occurred with ferrozine and ferene. Interference due to contaminating haem was comparable with all agents. Bilirubin and carotene produced no interference. Profound reductions in colour development were noted with EDTA plasma.

Chromogenic Compounds↗

PubMed1988

Anaemia in pregnant Indian women in Johannesburg.

A study was performed in 100 subjects to determine the prevalence and cause of anaemia in pregnant Indian women in the Johannesburg area. The geometric mean serum ferritin concentration in all three trimesters of pregnancy was below 12 micrograms/l, with 43.3% of women in the first, 48.6% in the second and 80.0% in the third trimester having concentrations below this value. Estimation of body iron stores revealed a mean deficit of 265 mg iron in subjects in the third trimester, 20% of whom had iron deficiency anaemia. No difference in iron status was demonstrable in subjects from different religious backgrounds. Folate and vitamin B12 nutrition was adequate. Three subjects were diagnosed as being beta-thalassaemia heterozygotes. The findings underline the need for routine iron supplementation of pregnant Indian women in the Johannesburg area.

Adolescent↗

PubMed1988

A screening test for detecting iron overload in population studies.

A simple, robust, inexpensive and reasonably accurate screening test, which involves colorimetric assessment of the unsaturated iron-binding capacity, was used to detect significant degrees of iron overload in a field setting. It was used in a survey of 152 men aged over 40 years who had previously been identified as having serum ferritin values above 400 micrograms/l and who were therefore potentially homozygous carriers of the HLA-linked iron-loading gene responsible for the clinical disorder idiopathic haemochromatosis (IHC). Such individuals almost always have a raised transferrin saturation and the screening test was compared with a standard method of measurement. The screening test accurately identified 7 out of 10 subjects with transferrin saturations above 62%. It also accurately identified 137 out of 142 subjects with saturation below 62%. There were 5 false-positive results; in all these subjects saturations were at the upper limit of normal or marginally raised. The test thus had a sensitivity of 77%, a specificity of 97%, an accuracy of 95% and a positive predictive accuracy of 67%. The test successfully identified a subgroup of subjects with serum ferritin values above 400 micrograms/l who appeared to have more severe degrees of iron overload. The screening test, which requires only 200 microliter serum and costs only 6.2 c, should not only be of potential value in identifying subjects at risk of developing the clinical manifestations of IHC but may prove even more useful in defining the prevalence of significant iron overload in the rural black population of South Africa.

Adult↗

PubMed1988

Nutritional anaemia in 11-year-old schoolchildren in the western Cape.

A nutritional anaemia survey was carried out on 610 11-year-old coloured, black and white schoolchildren in urban and rural communities in the western Cape. The mean (+/- 1 SD) haemoglobin concentration was 13.0 +/- 1.2 g/dl. The coloured and black subgroups considered together had a significantly lower mean haemoglobin concentration than the white subgroup (12.8 +/- 1.2 g/dl v. 13.4 +/- 1.0 g/dl) (F = 37.47; P less than 0.0001). The urban population as a whole had a significantly lower geometric mean (1 SD range) serum ferritin concentration than the rural population (25.6 (13.5-48.6) micrograms/l v. 34.1 (21.3-54.6) micrograms/l) (F = 42.94; P less than 0.0001). The lowest geometric mean serum ferritin values were found in the urban coloured (23.1 (11.5-46.4) micrograms/l) and urban black schoolchildren (23.7 (13.2-42.6) micrograms/l), with figures of less than 12 micrograms/l in 11.7% and 12.5% respectively. Although 28% of the children had red cell folate values below the recommended lower limit of normal (175 ng/ml), probability plot analysis of the data suggested that folate deficiency was not a major problem in the study population. The calculated daily iron and folate intakes were below the age-related recommended dietary allowance (RDA) in all the subgroups, yet anaemia was relatively uncommon. These findings suggest that the RDA values are too high. Overall the prevalence of nutritional anaemia was low and only the urban coloured subgroup showed significant second populations with low haemoglobin and serum ferritin measurements.

Black or African American↗

PubMed1988

Nutritional anaemia in pregnant coloured women in Johannesburg.

A nutritional anaemia survey was carried out in 224 pregnant coloured first-time attenders at Coronation Hospital antenatal clinic in Johannesburg during the second quarter of 1986. None had received any form of nutritional supplementation during pregnancy. Haemoglobin concentrations less than 11 g/dl were present in 18.9% of women in the third trimester of pregnancy, while 64% had a saturation of transferrin value of less than 16% and 68% a serum ferritin level less than 12 micrograms/l. Calculations suggested that mean iron stores in the first trimester were 228 mg, with 37.5% of women having absent stores. Comparable figures in the second and third trimesters were 74 mg and -92 mg respectively. The fact that many were iron deficient in the first trimester indicates a high frequency of iron deficiency in non-pregnant women in this population group. Although 20.8% of the women had red cell folate values below the normal range for non-pregnant subjects, folate deficiency did not appear to be a significant problem. Vitamin B12 deficiency was very uncommon.

Adolescent↗

PubMed1988

Phenotypic expression of the HLA-linked iron-loading gene in the Afrikaner population of the western Cape.

A previous study conducted on a group of Afrikaans-speaking subjects in the south-western Cape indicated a high frequency (0.115) of the HLA-linked iron-loading gene which causes idiopathic haemochromatosis. The results of phenotypic and genotypic studies on the first degree relatives of identified homozygotes and heterozygotes are now reported. There was considerable heterogeneity of phenotypic expression in the group of heterozygotes, with overlap between the homozygous and heterozygous subjects. The heterozygous relatives of heterozygous index cases, who had been identified on the basis of a serum ferritin concentration greater than 400 micrograms/l, appeared to have more frequent and more marked abnormalities of iron measurements than the heterozygote relatives of homozygous index cases (serum ferritin value greater than 400 micrograms/l, percentage transferrin saturation greater than 60). This suggests that the screening test was identifying a group of more significantly affected heterozygotes, with biochemical abnormalities that overlapped with the identified homozygotes. The index cases were followed up over a period of 5 years and during this time the 7 subjects diagnosed as heterozygotes showed a progressive increase in serum ferritin concentrations, which suggests some iron accumulation. Individual pedigrees included instances of gene recombination within the major histocompatibility complex, and of probable false-positive genotype assignment. The overall results confirm a high frequency of the gene in this particular community.

Adult↗

PubMed1988

Effect of ferrous and ferric chelators on transferrin-iron-macrophage interactions.

A study was done to evaluate the effect of ferrous and ferric chelators on the interaction between transferrin-iron and cultured human blood monocytes. This interaction has been previously shown to involve a specific receptor and vesicle protonation. Transferrin-iron uptake was significantly inhibited by the hydrophobic ferrous chelator 2,2' bipyridine, and the inhibition was shown not to be a consequence of the mobilisation of intracellular iron by the chelator. Chase experiments and prolonged incubation studies suggested that the chelator prevented the iron released from transferrin from negotiating the unit membrane. The iron and transferrin then appeared to be returned independently to the incubation medium. In contrast, a hydrophilic ferrin chelator, desferrioxamine, had only a very modest effect on the interaction. These findings are compatible with the hypothesis that transferrin-iron is reduced to the ferrous state during its uptake by the culture human blood monocyte.

2,2'-Dipyridyl↗