Malabsorption of protein bound vitamin B12.

Patients with subnormal serum vitamin B12 concentrations were tested for absorption of protein bound vitamin B12 and compared with controls. Absorption of the protein bound vitamin appeared to decrease with increasing age in healthy subjects. Differences between the result of this test and the result of the Schilling test in patients who had undergone gastric surgery were confirmed; such differences were also seen in some patients who had iron deficiency anaemia, an excessive alcohol intake, or folate deficiency. Defective absorption was also found in six patients with an adequate dietary intake of vitamin B12, normal Schilling test results, low serum vitamin concentrations, and tissue changes responding to treatment with vitamin B12. Malabsorption of the vitamin from protein bound sources, which is not detected by the Schilling test, may produce vitamin B12 deficiency of clinical importance.     

Experimental iron deficiency in Syrian hamsters (Mesocricetus auratus)

An animal model was developed in which the effect of iron deficiency on the oral mucosa could be studied. Iron deficiency was induced by feeding hamsters a low-iron powdered diet together with withdrawal of 0.5 ml of blood weekly, for a period of 9 weeks. At the end of this period the mean haematological values for control animals were, Hb 15.9 g/dl, plasma iron 40.3 mumol/l, TIBC 90.5 mumol/l and transferrin saturation 44.5%, compared with 7.4, 7.2, 111.4 and 6.5 respectively for experimental animals. These results were reproducible in successive groups of animals and indicate that this is a useful model for the study of iron deficiency anaemia.     

Disparity between dietary iron intake and iron status of children aged 10-12 years

Iron status was assessed in a representative sample of 188 adolescents living in a medium-sized city in Poland. Dietary intakes were evaluated using records of diet over a period of seven consecutive days. Subjects were considered to be iron deficient when two or more of the following parameters were abnormal: serum ferritin, transferrin saturation or mean corpuscular haemoglobin concentration. Based on this definition, the prevalence of iron deficiency in the investigated sample of children aged from ten to twelve years was 12.7%. Iron deficiency anaemia was defined using the following criteria: haemoglobin values less than 12.0 g. dl (-1) in girls or less than 12.2 g. dl(-1) in boys, combined with an iron deficiency. With such a definition, the prevalence of iron deficiency anaemia in all subjects was 6.3%. Four boys (3.9%) and six girls (6.8%) were diagnosed as anaemic. The values for Hb in the anaemic boys ranged from 10.9 to 12.2 g. dl (-1) and in anaemic girls from 8.7 to 12.0 g. (-1). It was found that the majority of the individuals studied had a dietary haem-iron intake lower than that recommended. No relationship was found between the level of serum ferritin and total iron and vitamin C dietary intake, but there was positive correlation between serum ferritin and intake of haem iron. A seven-day dietary history questionnaire correctly identified children at risk of iron deficiency anaemia.     

Increased Gastric IL-1β Concentration and Iron Deficiency Parameters in H. pylori Infected Children

Association between H. pylori infection, iron deficiency and iron deficiency anaemia has been described, but the mechanisms involved have not been established. We hypothesized that in H. pylori infected children increased gastric concentrations of IL-1β and/or TNF-α, both potent inhibitors of gastric acid secretion that is essential for iron absorption, are predictors for low blood concentrations of ferritin and haemoglobin, markers of early depletion of iron stores and anaemia, respectively. We evaluated 125 children undergoing endoscopy to clarify the origin of gastrointestinal symptoms. Gastric specimens were obtained for H. pylori status and cytokine evaluation and blood samples for determination of iron deficiency/iron deficiency anaemia parameters and IL1 cluster and TNFA polymorphisms that are associated with increased cytokine secretions. Higher IL-1β and TNF-α gastric concentrations were observed in H. pylori-positive (n = 47) than in -negative (n = 78) children. Multiple linear regression models revealed gastric IL-1β, but not TNF-α, as a significant predictor of low ferritin and haemoglobin concentrations; results were reproduced in young children in whom IL1RN polymorphic genotypes associated with higher gastric IL-1β expression and lower blood ferritin and haemoglobin concentrations. In conclusion, high gastric levels of IL-1β can be the link between H. pylori infection and iron deficiency/iron deficiency anaemia in childhood.     

Absorption of non-haem iron from food during normal pregnancy.

OBJECTIVE--To determine whether the increased iron demands of pregnancy could be met by increased absorption from dietary sources. DESIGN AND SETTING--Longitudinal prospective study in the research unit of a maternity hospital. SUBJECTS--12 normal pregnant women. INTERVENTIONS--At 12, 24, and 36 weeks'' gestation (within one week) and 16-24 weeks after delivery women ate a breakfast of meat, bread, and orange juice (3.2 mg iron), extrinsically labelled with the stable isotope iron-54 (2.8 mg); the stable isotope iron-57 (200 micrograms) was given intravenously. MAIN OUTCOME MEASURES--Serum samples were taken for 10 hours after administration of the isotopes; ratios of the isotopes were measured by inductively coupled plasma mass spectrometry, and the absorption of oral iron was calculated. RESULTS--The geometric mean (95% confidence interval) absorption of iron at 12, 24, and 36 weeks'' gestation was 7% (5% to 11%), 36% (28% to 47%), and 66% (57% to 76%) respectively. At 16-24 weeks after delivery the absorption was 11% (6% to 21%). The mean increase in absorption at 36 weeks (compared with that at 12 weeks) was 9.1 times (6.0 to 13.7). One pregnant woman developed iron deficiency anaemia but was otherwise indistinguishable from the others. CONCLUSIONS--An increase in the absorption of iron from food is a physiological consequence of normal pregnancy, not the result of developing anaemia during pregnancy, and such an increase is large enough to meet the increased requirements of pregnancy provided that the dietary intake is adequate.     

The effect of changing living standards on iron status in pregnancy in Calabar urban.

Reduced meat intake is often associated with iron deficiency anaemia. Reduced meat intake that arose from the frugality associated with a prolonged period of national economic reorientation policy, known as the "structural adjustment programme" (SAP), may have placed iron-stress on pregnancy in particular. Iron status of pre-SAP and SAP pregnancies were established from measurement of the haematological values of subjects. Indices such as haemoglobin (Hb), packed cell volume, serum Fe were lower in pregnancy especially during SAP. However, SAP pregnancy serum ferritin did not respond significantly to iron depletion. Unlike PCV, Total Iron Binding Capacity (TIBC) and serum transferrin values showed a reverse behaviour. The level of these values, however, portends a toll exerted on body iron status in pregnancy associated with reduced haem iron intake. The changes in these values did not, however, lead to any over symptoms of iron deficiency probably because increased sea food (molluscs) consumption ameliorates the iron-toll from low absorbed non-haem iron. For lower income rural women in non-coastal areas, the absence of seafood in their diets exacerbates the low iron status in Pregnancy.     

Intrinsic-factor Antibody and Absorption of Vitamin B12 in Pernicious Anaemia

The mean urinary excretion in a vitamin-B₁₂ absorption (Schilling) test in control subjects was 19·2% and in pernicious anaemia when given with additional intrinsic factor was as follows: no intrinsic-factor antibodies demonstrable 19·3%, antibodies in serum only 14·4%, antibodies in gastric juice only 11·1%, and antibodies in both serum and gastric juice 8·4%. It is concluded that intrinsic-factor antibody exerts an adverse effect on vitamin-B₁₂ absorption in most patients with pernicious anaemia.     

Anemia in female adolescents]

Investigations for exploring the frequency and pathogenesis of anaemia were carried out in 164 female pupils of a minicipal grammar school for girls aged from 14 to 20 years. There were lowered haematocrit values below 37% in 81 cases (49%), which were due to iron deficiency in 31 girls. Only in one case a lowered vitamin B12 level was detected and in 8 girls there was a lowered folic acid content in the serum. The frequency of anaemia in girls of school age mainly caused by iron deficiency is emphasized.     

Ferritin in bone marrow and serum in iron deficiency and iron overload

Nonheme iron and ferritin in the bone marrow and serum ferritin was investigated in patients with iron deficiency anaemia or iron overload. As controls served patients without any disturbance of the iron metabolism. There is a precise correlation between the nonheme iron and ferritin in the bone marrow of patients with and without disturbance of iron metabolism. A correlation was also found between the ferritin in the bone marrow and the serum. Nonheme iron and ferritin in the bone marrow and serum ferritin was decreased in patients with iron deficiency anaemia. Conversely, the same parameters were increased in patients with iron overload.     

Gastric Helicobacter Infection Induces Iron Deficiency in the INS-GAS Mouse

There is increasing evidence from clinical and population studies for a role of H. pylori infection in the aetiology of iron deficiency. Rodent models of Helicobacter infection are helpful for investigating any causal links and mechanisms of iron deficiency in the host. The aim of this study was to investigate the effects of gastric Helicobacter infection on iron deficiency and host iron metabolism/transport gene expression in hypergastrinemic INS-GAS mice. INS-GAS mice were infected with Helicobacter felis for 3, 6 and 9 months. At post mortem, blood was taken for assessment of iron status and gastric mucosa for pathology, immunohistology and analysis of gene expression. Chronic Helicobacter infection of INS- GAS mice resulted in decreased serum iron, transferrin saturation and hypoferritinemia and increased Total iron binding capacity (TIBC). Decreased serum iron concentrations were associated with a concomitant reduction in the number of parietal cells, strengthening the association between hypochlorhydria and gastric Helicobacter-induced iron deficiency. Infection with H. felis for nine months was associated with decreased gastric expression of iron metabolism regulators hepcidin, Bmp4 and Bmp6 but increased expression of Ferroportin 1, the iron efflux protein, iron absorption genes such as Divalent metal transporter 1, Transferrin receptor 1 and also Lcn2 a siderophore-binding protein. The INS-GAS mouse is therefore a useful model for studying Helicobacter-induced iron deficiency. Furthermore, the marked changes in expression of gastric iron transporters following Helicobacter infection may be relevant to the more rapid development of carcinogenesis in the Helicobacter infected INS-GAS model.     

Effect of Helicobacter pylori Infection on Iron Absorption in Asymptomatic Adults Consuming Wheat Flour Fortified with Iron and Zinc

Helicobacter pylori infection could impair iron absorption from fortified products. The objective of the study was to determine the effect of H. pylori infection on iron absorption from asymptomatic adults consuming wheat flour fortified with iron and zinc. The (13)C urea breath test was used to assess H. pylori infection. Twenty-four H. pylori-positive and 26 H. pylori-negative volunteers completed the study. On day?1, the subjects were randomized to receive for breakfast bread fortified with either ferrous sulfate and zinc sulfate or ferrous fumarate and zinc oxide. Bread fortified with ferrous sulfate was labeled with (59)Fe as sulfate, and bread fortified with ferrous fumarate was labeled with (55)Fe as fumarate. On day?3, they received the other type of bread, with the respective tracers. On days?18-23, a proton pump inhibitor was administered to all subjects. On day?24, all subjects received bread fortified with ferrous fumarate and zinc oxide labeled with (55)Fe as fumarate. H. pylori prevalence was 77.6%. The geometric mean (±1?SD) of iron absorption was significantly higher for ferrous sulfate than fumarate (6.9?±?2.9% vs. 0.5?±?3.5%, p?相似文献   

Non-transferrin-bound iron in plasma following administration of oral iron drugs

Non-transferrin-bound iron (NTBI) was detected in serum samples from volunteers with normal iron stores or from patients with iron deficiency anaemia after oral application of pharmaceutical iron preparations. Following a 100 mg ferrous iron dosage, NTBI values up to 9 μM were found within the time period of 1–4 h after administration whereas transferrin saturation was clearly below 100%. Smaller iron dosages (10 and 30 mg) gave lower but still measurable NTBI values. The physiological relevance of this finding for patients under iron medication has to be elucidated.     

Absorption of Slow-release Iron and Effects of Ascorbic Acid in Normal Subjects and after Partial Gastrectomy

Radiolabelled tablets of slow-release iron and ferrous sulphate containing 50 mg of elemental iron were given to 28 patients, and iron absorption was studied using a whole body counter.There was no significant difference between the absorption of ferrous sulphate and that of slow-release iron in normal subjects, anaemic patients, anaemic and non-anaemic post-gastrectomy patients, or those with coeliac disease. Ascorbic acid potentiated iron absorption, especially in anaemic post-gastrectomy patients.The indications and hazards of slow release iron preparations are discussed.     

Red cell ferritin content: a re-evaluation of indices for iron deficiency in the anaemia of rheumatoid arthritis.

In iron deficiency anaemia basic red cell content of ferritin is appreciably reduced. This variable was determined in 62 patients with rheumatoid arthritis to evaluate conventional laboratory indices for iron deficiency in the anaemia of rheumatoid arthritis. For 23 patients with rheumatoid arthritis and normocytic anaemia irrespective of plasma ferritin concentration, red cell ferritin content did not differ significantly from that for non-anaemic patients with rheumatoid arthritis. For 27 patients with rheumatoid arthritis and microcytic anaemia, the mean red cell ferritin content for patients with a plasma ferritin concentration in the 13-110 micrograms/l range was appreciably reduced. It was indistinguishable from that for patients with rheumatoid arthritis and classical iron deficiency anaemia, indicated by plasma ferritin concentrations of less than 12 micrograms/l. In contrast, the mean red cell ferritin content for patients with rheumatoid arthritis, microcytic anaemia, and plasma ferritin concentrations above 110 micrograms/l did not differ from that for patients with rheumatoid arthritis and normocytic anaemia. Oral treatment with iron in patients with rheumatoid arthritis, microcytic anaemia, and appreciably reduced red cell ferritin concentrations was accompanied by significant increases in haemoglobin concentration (p less than 0.01), mean corpuscular volume (p less than 0.01), and red cell ferritin contents (p less than 0.05). This treatment, however, did not produce any appreciable change in haemoglobin concentration in patients with rheumatoid arthritis, normocytic anaemia, and normal red cell ferritin contents. These findings suggest that the indices for iron deficiency in patients with rheumatoid arthritis and anaemia should include peripheral blood microcytosis together with a plasma ferritin concentration of less than 110 micrograms/l.     

Iron in bone marrow

In the bone-marrow, non-haemoglobin iron can predominantly be found in the reticulum. Slight granules containing iron can also be observed in parts of erythroblasts by means of the Berlin blue reaction. These cells are called sideroblasts. In chemical respect, non-haemoglobin iron consists of ferritin soluble in water and haemosiderin insoluble in water. Erythroblasts will only take their iron from plasma transferrin. For the most part, this iron uptake is being regulated by erythropoietin adapting erythropoiesis to the oxygen requirements of the tissue. The iron contained in erythroblasts is predominantly utilized for haemoglobin synthesis in these cells. A slight part is being taken up by ferritin. The bone-marrow reticulum will phagocytise aged erythrocytes and store liberated iron as ferritin and haemosiderin. Part of the iron is being delivered again to plasma transferrin. With constant serum iron level the liberation of iron from the reticulo-endothelial tissue must correspond to the iron uptake by erythropoiesis. The absence of iron capable of being coloured in the bone-marrow reticulum is considered to be a reliable parameter of iron deficiency. It enables the diagnosis of iron deficiency anaemia to be made even in those patients with serum iron level and a total iron binding capacity lying within the normal range and no hypochromia of erythrocytes being present. It enables iron deficiency anaemia to be separated from sideropenic anaemia with reticulo-endothelial siderosis in differential-diagnostic manner. Even in patients with sideroblastic anaemia, iron colouring of bone-marrow smears is required for ensuring the diagnosis. Recently, a separation has also been made for idiopathic anaemia with abnormal sideroblasts. In these patients there is an increased risk for acute leukemia to develop.     

Further Observations on the Relation between Iron and Folate Status in Pregnancy

This study was planned to determine whether iron deficiency in pregnancy predisposed to the development of folate deficiency and also the smallest daily iron supplement that maintained haemoglobin levels in pregnancy.Three groups of women were given oral ferrous fumarate supplying 30, 60, and 120 mg of iron; a fourth group was given 1 g of parenteral iron in early pregnancy followed by oral iron (60 mg); a fifth group received a placebo. Tablets were taken once daily.Oral iron 30 mg once daily maintained haemoglobin levels throughout pregnancy. Women whose marrows lacked demonstrable iron at the 37th week had a significantly higher incidence of megaloblastic haemopoiesis (28·7%) than those with demonstrable iron stores (15·3%); women taking oral iron did not have a lower frequency of megaloblastosis than those given a placebo. We concluded that iron does not have a direct effect on folate status in pregnancy, that the association of iron deficiency and megaloblastic anaemia in pregnancy is the result of poor nutrition, and that there is no cause-and-effect relation between them.     

Serum ferritin in patients with various haemolytic disorders.

174 serum ferritin assays in 121 patients with various haemolytic disorders have been performed. The mean serum ferritin levels were significantly increased in all these disorders in contrast to healthy controls. The highest serum ferritin levels were found in pyruvate kinase (PK) deficiency, moderate increase was observed in hereditary sphaerocytosis (HS) and in autoimmune haemolytic anaemia (AIHA) with massive haemolysis and in glucose-6-phosphate dehydrogenase (G-6-PD) deficiency. Mild elevation of serum ferritin levels was depicted in paroxysmal nocturnal haemoglobinuria (PNH), in beta thalassaemia minor and in other types of haemoglobinopathies. The range of values was associated with a degree of haemolysis and its relation to duration of the disease was not apparent in most cases. Highly significant differences between serum ferritin levels in splenectomized and non-splenectomized patients with HS and between serum ferritin levels in patients with AIHA with massive haemolysis or in remission were found. As compared to normal controls, significant increase of serum ferritin levels was observed even in patients with AIHA in remission or in splenectomized patients with HS. In two patients with PK deficiency the levels exceeding 2,000 micrograms/l indicated manifest iron overload. A reliability of serum ferritin assay as an index of iron stores in haemolytic disorders has been discussed.     

Complex genesis of anemia in chronic liver diseases]

36% of a total of chronic liver patients suffered from anaemia and 50.5% of patients affected with liver cirrhosis. In most cases the anaemias were normochrome and hypochrome or hyperchrome only in some cases. In analyzing possible single factors the reductions of vitamin B12 absorption could be made probable by means of the Schilling test and sometimes a folic acid deficiency in macrocyte anaemia with normal vitamin B12 absorption by determining the folic acid content in the serum and by successes of test treatment 82% of patients with liver cirrhosis showed a latent or manifest haemolysis. However, it was only in 1/3 of the patients with liver cirrhosis that the spleen turned out to be the place of an increased degradation of erythrocytes. In some cases an increased erythrocytoclasia into the liver could be identified. Predominantly, however, an increased degradation of erythrocytes in the total RHS had to be assumed. Twice an ineffective erythropoiesis could be found by ferrokinetic examinations. As a whole ferrokinetic examinations cannot be interpreted easily, because their static and dynamic values of iron transport in the plasma volume of liver patients will undergo considerable changes. Patients with disturbances of haematopoiesis and with haemolysis remaining in the latent stage may develop a manifest anaemia because of the influence of additional factors, such as increase of the plasma volume at lowered haematocrit value or microbleedings. The cause of anaemia cannot be concluded with sufficient probability from the type of anaemia; in a single case all pathogenetic factors will rather have to be analyzed. Therapeutic possibilities for hepatogenous anaemia of complex genesis are discussed.     

Relationship between Hb and HbA2 concentrations in healthy and iron deficient subjects.

In 23 healthy subjects and in 115 patients with various degrees of chronic iron deficiency anaemia without congenital abnormalities of globin synthesis, Hb ranged from 3.4 to 16.3 g/100 ml. HbA2 ranged from 0.0550 to 0.5250 g/100 ml. Hb and HbA2 were statistically correlated, as shown by linear regression analysis (a equals --0.1387; b equals 0.0372; r equals 0.8198; P smaller than 0.001). The second degree parabola was not statistically different, but it gave a biologically preferable Figure for intercept (a equals --0.0006; b equals 0.0070; c equals 0.0015; r equals 0.8324; P smaller than 0.001). The second degree parabola was to be preferred also on the basis of previous literature results. Shortness of iron seems to reduce more the HbA2 than the Hb levels.