Transepithelial transport of glucose and mRNA of glucose transporters in the small intestine of rats with iron-deficiency anemia

Objective: To evaluate the transepithelial transport of sodium, glucose, potassium, and water and the mRNA level of the sodium-glucose cotransporter (SGLT1) and the facilitated sugar transporter (GLUT2) in the small intestine of iron-deficient rats. Methods: After 6 wk of receiving diets with low or normal iron content, rats (Wistar-EPM) were subjected to two experiments: 1) evaluation of the transepithelial transport of sodium, glucose, potassium, and water by an ""in vivo"" experimental model of intestinal perfusion and 2) determination of relative SGLT1 and GLUT2 mRNA levels in the proximal, intermediate, and distal portions of the small intestine by the northern blotting technique. Results: Hemoglobin and hepatic iron levels were statistically lower in the anemic rats. The mean transepithelial transports of sodium (-33.0 mu Eq . min(-1) . cm(-1)), glucose (426.0 mu M . min(-1) . cm(-1)), and water (0.4 mu L . min(-1) . cm(-1)) in the small intestine of the anemic rats were significantly lower than in the control group (349.1 mu Eq . min(-1) cm(-1), 842.6 mu M . min(-1) . cm(-1), and 4.3 mu l . min(-1) cm(-1), respectively, P < 0.05). The transepithelial transport of potassium was similar for both groups. The relative SGLT1 mRNA levels of the anemic rats in the intermediate (1.796 +/- 0.659 AU) and distal (1.901 +/- 0.766 AU) segments were significantly higher than the values for the control rats (intermediate 1.262 +/- 0.450 AU, distal 1.244 +/- 0.407 AU). No significant difference was observed for the relative SLGT1 mRNA levels in the proximal segment or for the GLUT2 mRNA levels in all segments. Conclusion: Iron deficiency decreases the absorption of glucose, sodium, and water and increases SGLT1 mRNA in the intermediate and distal segments of the small intestine of rats. (C) 2011 Elsevier Inc. All rights reserved.

Helicobacter pylori and Iron-deficiency Anemia in Adolescents in Brazil

Aim: The aim of the study was to evaluate the association between Helicobacter pylori infection and iron deficiency (ID) in adolescents attending a public school. Patients and Methods: From March to June 2001, a cross-sectional study was conducted among adolescents (10-16 years) enrolled in a single public school in Sao Paulo, Brazil. Of 400 eligible students, 195 agreed to participate, but 1 was excluded due to sickle cell disease. A blood sample was collected from each subject to measure hemoglobin and ferritin. H pylori status was investigated with the 13 C-urea breath test. All of the subjects with either anemia or ID were given iron therapy. Results: H pylori prevalence was 40.7% (79/194), being higher in male subjects (45/90 vs 34/104, P = 0.014). There was no relation between infection and nutritional status. Abnormally low serum ferritin was observed in 12 subjects, half of whom were positive for H pylori (odds ratio [OR] 1.49, 95% confidence interval [CI] 0.38-5.81). The median serum ferritin was 33.6 ng/mL (interquartile range 23.9-50.9) in infected subjects and 35.1 ng/mL (interquartile range 23.7-53.9) in uninfected subjects. Anemia was detected in 2% (4/194) of the students, half of whom were infected (OR 1.47, 95% CI 0.1-20.6). The mean hemoglobin value in infected subjects was 13.83 g/dL +/- 1.02 versus 14 g/dL +/- 1.06 in uninfected subjects. Conclusions: The study was not able to find a relation between H pylori infection and ID or anemia.

[A young child with acute abdomen and iron deficiency anemia]

The case of a 20 month-old girl that was admitted to the emergency ward because of worsening of her general condition in the setting of acute non-bloody gastroenteritis is reported. The clinical examination revealed signs of severe dehydration and a prominent tender abdomen. Laboratory evaluation showed leucocytosis, elevated C-reactive protein and severe hypochromic microcytic anemia. Abdominal X-ray revealed diffuse meteorism. The child underwent laparascopic evaluation. A perforated Meckel's diverticulum was found. Perforation and anemia due to occult bleeding are unusual presentations of Meckel's diverticulum. The differential diagnosis of children presenting with an acute abdomen with special focus on Meckel's diverticulum is discussed.

Treatment of iron deficiency with intravenous ferric carboxymaltose in general practice: a retrospective database study.

BACKGROUND Iron deficiency is a frequent problem in general practice. Oral supplementation may in some cases not be well tolerated or not be efficient. Intravenous ferric carboxymaltose may be an alternative for iron supplementation in general practice. The aim of the present study was to analyze the indications for and the efficacy of intravenous ferric carboxymaltose in a primary care center. METHODS We retropectively analyzed electronic data from 173 patients given intravenous ferric carboxymaltose between 2011 and 2013 in primary care center with 18 GPs in Bern, Switzerland. RESULTS Of all patients, 34% were treated intravenously due to an inappropriate increase in ferritin levels after oral therapy, 24% had side effects from oral treatment, 10% were treated intravenously due to the patients explicit wish, and in 39% of all cases, no obvious reason of intravenous instead of oral treatment could be found. Intravenous ferric carboxymaltose led to a significant increase in hemoglobin and serum ferritin levels. Side effects of intravenous treatment were found in 2% of all cases. CONCLUSION We conclude that treatment with intravenous ferric carboxymaltose is an efficient alternative for patients with iron deficiency in general practice, when oral products are not well tolarated or effective. As treatment with iron carboxymaltose is more expensive and potentially dangerous due to side effects, the indication should be placed with (more) care.

SOCIAL AND BIOLOGICAL DETERMINANTS OF SHORT-TERM GROWTH VELOCITY AMONG PRESCHOOLERS OF RURAL GUATEMALA: A PATH ANALYSIS APPROACH (WEIGHT-GAIN, IRON DEFICIENCY, GASTROINTESTINAL SYMPTOMS)

This dissertation develops and tests through path analysis a theoretical model to explain how socioeconomic, socioenvironmental, and biologic risk factors simultaneously influence each other to further produce short-term, depressed growth in preschoolers. Three areas of risk factors were identified: child's proximal environment, maturational stage, and biological vulnerability. The theoretical model represented both the conceptual framework and the nature and direction of the hypotheses. Original research completed in 1978-80 and in 1982 provided the background data. It was analyzed first by nested-analysis of variance, followed by path analysis. The study provided evidence of mild iron deficiency and gastrointestinal symptomatology in the etiology of depressed, short-term weight gain. Also, there was evidence suggesting that family resources for material and social survival significantly contribute to the variability of short-term, age-adjusted growth velocity. These results challenge current views of unifocal intervention, whether for prevention or control. For policy formulations, though, the mechanisms underlying any set of interlaced relationships must be decoded. Theoretical formulations here proposed should be reassessed under a more extensive research design. It is suggested that studies should be undertaken where social changes are actually in progress; otherwise, nutritional epidemiology in developing countries operates somewhere between social reality and research concepts, with little grasp of its real potential. The study stresses that there is a connection between substantive theory, empirical observation, and policy issues. ^

SEVERITY OF IRON DEFICIENCY ANEMIA AND ITS RELATIONSHIP TO GROWTH AND MORBIDITY IN A POPULATION OF PRE-SCHOOLERS IN RURAL GUATEMALA (IRON DEFICIENCY, MORBIDITY, GROWTH)

The objectives of this study were to determine the nature of the relationship between severity of iron deficiency anemia, response to iron treatment, respiratory and gastrointestinal illness and weight change. Seventy-five pre-school children from rural Guatemala received daily oral iron therapy for an eleven week period, and were classified into one of three groups having different degrees of iron deficiency anemia. Anthropometric and biochemical data were collected prior and after iron treatment; morbidity data were collected throughout the period of treatment. The outcome variables were percentage weight change, percentage of total days ill with any type of symptom, percentage of total days ill with gastrointestinal symptoms, percentage of total days ill with respiratory symptoms, percentage of total days ill with combination syndrome symptoms. Age, sex and socio-economic status, were independent of any of the independent or outcome variables used. On the other hand, the level of hemoglobin covaried with the height of the children, the smallest children were the most severely anemic. The relationships between hemoglobin levels and weight change, frequency of morbidity (gastrointestinal, respiratory and combination syndrome) and total number of days ill with any symptomatology were investigated. No statistical significance was found in these analyses except when contrasting children with normal hemoglobin levels to iron deficient children, where the findings indicated the normal children experienced more gastrointestinal morbidity. The same relationship were again analyzed but including delta hemoglobin as covariate in the analysis, this latter one was found to be significant at 7% when the percentage of days ill from gastrointestinal morbidity was tested against the hemoglobin groups. The relationship found indicates that, all other covariates accounted for, the percentage of days ill from gastrointestinal morbidity will decrease approximately 1% for each 1% increase in delta of hemoglobin. ^

The Role of Iron-Deficiency Stress Responses in Stimulating Heavy-Metal Transport in Plants1

Plant accumulation of Fe and other metals can be enhanced under Fe deficiency. We investigated the influence of Fe status on heavy-metal and divalent-cation uptake in roots of pea (Pisum sativum L. cv Sparkle) seedlings using Cd2+ uptake as a model system. Radiotracer techniques were used to quantify unidirectional 109Cd influx into roots of Fe-deficient and Fe-sufficient pea seedlings. The concentration-dependent kinetics for 109Cd influx were graphically complex and nonsaturating but could be resolved into a linear component and a saturable component exhibiting Michaelis-Menten kinetics. We demonstrated that the linear component was apoplastically bound Cd2+ remaining in the root cell wall after desorption, whereas the saturable component was transporter-mediated Cd2+ influx across the root-cell plasma membrane. The Cd2+ transport system in roots of both Fe-deficient and Fe-sufficient seedlings exhibited similar Michaelis constant values, 1.5 and 0.6 μm, respectively, for saturable Cd2+ influx, whereas the maximum initial velocity for Cd2+ uptake in Fe-deficient seedlings was nearly 7-fold higher than that in Fe-grown seedlings. Investigations into the mechanistic basis for this response demonstrated that Fe-deficiency-induced stimulation of the plasma membrane H+-ATPase did not play a role in the enhanced Cd2+ uptake. Expression studies with the Fe2+ transporter cloned from Arabidopsis, IRT1, indicated that Fe deficiency induced the expression of this transporter, which might facilitate the transport of heavy-metal divalent cations such as Cd2+ and Zn2+, in addition to Fe2+.

Formate Dehydrogenase, an Enzyme of Anaerobic Metabolism, Is Induced by Iron Deficiency in Barley Roots1

To identify the proteins induced by Fe deficiency, we have compared the proteins of Fe-sufficient and Fe-deficient barley (Hordeum vulgare L.) roots by two-dimensional polyacrylamide gel electrophoresis. Peptide sequence analysis of induced proteins revealed that formate dehydrogenase (FDH), adenine phosphoribosyltransferase, and the Ids3 gene product (for Fe deficiency-specific) increased in Fe-deficient roots. FDH enzyme activity was detected in Fe-deficient roots but not in Fe-sufficient roots. A cDNA encoding FDH (Fdh) was cloned and sequenced. Fdh expression was induced by Fe deficiency. Fdh was also expressed under anaerobic stress and its expression was more rapid than that induced by Fe deficiency. Thus, the expression of Fdh observed in Fe-deficient barley roots appeared to be a secondary effect caused by oxygen deficiency in Fe-deficient plants.

Effect of commercial amino acids on iron nutrition of tomato plants grown under lime-induced iron deficiency

The objective of this work was to study the effect of root and foliar application of two commercial products containing amino acids from plant and animal origin on iron (Fe) nutrition of tomato seedlings cultivated in two nutrient media: lime and normal nutrient solutions. In the foliar-application experiment, each product was sprayed with 0.5 and 0.7 mL L–1 2, 7, 12, and 17 d after transplanting. In the root application experiment, 0.1 and 0.2 mL L–1 of amino acids products were added to the nutrient solutions. In both experiments, untreated control plants were included as well. Foliar and root application of the product containing amino acids from animal origin caused severe plant-growth depression and nonpositive effects on Fe nutrition were found. In contrast, the application of the product from plant origin stimulated plant growth. Furthermore, significantly enhanced root and leaf FeIII-chelate reductase activity, chlorophyll concentration, leaf Fe concentration, and FeII : Fe ratio were found in tomato seedlings treated with the product from plant origin, especially when the amino acids were directly applied to the roots. These effects were more evident in plants developed under lime-induced Fe deficiency. The positive results on Fe uptake may be related to the action of glutamic acid, the most abundant amino acid in the formulation of the product from plant origin.

Knock-out of Arabidopsis metal transporter gene IRT1 results in iron deficiency accompanied by cell differentiation defects

IRT1 and IRT2 are members of the Arabidopsis ZIP metal transporter family that are specifically induced by iron deprivation in roots and act as heterologous suppressors of yeast mutations inhibiting iron and zinc uptake. Although IRT1 and IRT2 are thought to perform redundant functions as root-specific metal transporters, insertional inactivation of the IRT1 gene alone results in typical symptoms of iron deficiency causing severe leaf chlorosis and lethality in soil. The irt1 mutation is characterized by specific developmental defects, including a drastic reduction of chloroplast thylakoid stacking into grana and lack of palisade parenchyma differentiation in leaves, reduced number of vascular bundles in stems, and irregular patterns of enlarged endodermal and cortex cells in roots. Pulse labeling with 59Fe through the root system shows that the irt1 mutation reduces iron accumulation in the shoots. Short-term labeling with 65Zn reveals no alteration in spatial distribution of zinc, but indicates a lower level of zinc accumulation. In comparison to wild-type, the irt1 mutant responds to iron and zinc deprivation by altered expression of certain zinc and iron transporter genes, which results in the activation of ZIP1 in shoots, reduction of ZIP2 transcript levels in roots, and enhanced expression of IRT2 in roots. These data support the conclusion that IRT1 is an essential metal transporter required for proper development and regulation of iron and zinc homeostasis in Arabidopsis.

Decreased hephaestin activity in the intestine of copper-deficient mice causes systemic iron deficiency

Copper and iron metabolism intersect in mammals. Copper deficiency simultaneously leads to decreased iron levels in some tissues and iron deficiency anemia, whereas it results in iron overload in other tissues such as the intestine and liver. The copper requirement of the multicopper ferroxidases hephaestin and ceruloplasmin likely explains this link between copper and iron homeostasis in mammals. We investigated the effect of in vivo and in vitro copper deficiency on hephaestin (Heph) expression and activity. C57BL/6J mice were separated into 2 groups on the day of parturition. One group was fed a copper-deficient diet and another was fed a control diet for 6 wk. Copper-deficient mice had significantly lower hephaestin and ceruloplasmin (~50% of controls) ferroxidase activity. Liver hepcidin expression was significantly downregulated by copper deficiency (~60% of controls), and enterocyte mRNA and protein levels of ferroportin1 were increased to 2.5 and 10 times, respectively, relative to controls, by copper deficiency, indicating a systemic iron deficiency in the copper-deficient mice. Interestingly, hephaestin protein levels were significantly decreased to ~40% of control, suggesting that decreased enterocyte copper content leads to decreased hephaestin synthesis and/or stability. We also examined the effect of copper deficiency on hephaestin in vitro in the HT29 cell line and found dramatically decreased hephaestin synthesis and activity. Both in vivo and in vitro studies indicate that copper is required for the proper processing and/or stability of hephaestin.