Transferrin receptor distribution and iron deposition in the hepatic fobufe of iron-overloaded rats

Under the condition of obvious iron-overload, there is a zonal hernoeiderin (iron) deposition in hepatic lobules. The deposition is heavtest in the periporfal (zone 1) and lightest in the perivenws (zone 3) hepatocytes. However, the mechanism for this pattern of iron deposition is obscure. Hepatic tissues from control, iron-deficlent or ironoverloaded Wistar rats me used to study its pathogenesis. iron-deficiency was Induced by a low Iron regimen. Ironoverload was produced by repeated intraperitoneal injections of ferric nitrilotriace-We (Fe³⁺-NTA) for 1–4 months. Liver tissues of the rats were lmmunohistochemically and histochemically stained for tmnaferrin receptor (TfR), transferrin (Tf), ferritin (Ft), and iron. The staining intensity of TfR, Tf and Ft increased in hepatocytes of iron-deflctent rats and decreased in that of the iromverloaded in comparison with the control rats. TfR atalning was strong in zone 1, with gradual transition into weak staining in zone 3 hepatocytes of the rat liver. TfR located primarily on the hepatocyte membrane. Tf had both membranous and cytoplasmic distribution. Many hepatocytes in group B had strong cytoplasmic Tf staining. Conversely, only a few hepatocytes had weakly stained cytoplasmic Tf in group C. Hepatocytes and Kupffer cells were Ft positive in control rats. Ft was distributed only in the cytoplasm. The staining intensity of Ft was stronger in zone 3 than in zone 1 hepatocytes of iron-deficient rats. In iron-overloaded rats, the iron deposition was severe in zone 1 and mild in zone 3 hepatocytes. These findings suggest that uptake of iron into hepatocytes in vivo is regulated and mediated by TfR and Tf. Gradient TfR distribution from zone 1 to 3 hepatocytes and active TfR-Tf mediated iron uptake resuited in the zonal iron deposition in the hepatic lobule of iron-overloaded rats.     

Isolation and partial characterisation of neuronal growth cones from neonatal rat forebrain

We have devised a method for the isolation of viable neuronal growth cones from neonatal rat forebrain. The method involves differential and density gradient centrifugation and exploits the relatively low buoyant density (approximately 1.018 g/cm3) of growth cones. There are no known biochemical markers for growth cones and it was necessary therefore to monitor for their presence during the isolation using transmission electron microscopy. Several criteria were used to identify isolated growth cones including the presence of filopodia, an extensive system of branching, tubular smooth endoplasmic reticulum and a region rich in microfilaments subjacent to the plasma membrane. These morphological features are similar to those of growth cones identified unequivocally in intact developing brain and in tissue culture. Electron microscopical analysis showed that greater than 90% of membrane-bound, identifiable objects in one fraction were growth cones by these criteria. The major contaminant consisted of membrane sacs and vesicles of unidentified origin. There were only small amounts of isolated rough endoplasmic reticulum and mitochondria. Isolated growth cones were roughly spherical in shape with a diameter of 1.9 +/- 0.5 micron (mean +/- 1 SD). They usually contained mitochondria, large granular vesicles and small vesicles, and occasionally contained coated vesicles, lysosomes, lamellar bodies and multivesicular bodies, and only very rarely, intermediate filaments. Occasionally, growth cones had rudimentary synapses on them. The viability of isolated growth cones was investigated by observing their behaviour in short-term culture. After a few hours in culture on poly-D-lysine-coated coverslips, growth cones flattened down and extended filopodia-like processes. This behaviour was inhibited by cytochalasin B and reversibly by cold (4 degrees C). We conclude that physiologically active growth cones can be isolated rapidly and in large numbers by the method described here.     

Maternal Vitamin C and Iron Intake during Pregnancy and the Risk of Islet Autoimmunity and Type 1 Diabetes in Children: A Birth Cohort Study

Our aim was to study the associations between maternal vitamin C and iron intake during pregnancy and the offspring’s risk of developing islet autoimmunity and type 1 diabetes. The study was a part of the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) prospective birth cohort including children genetically at risk of type 1 diabetes born between 1997–2004. The diets of 4879 mothers in late pregnancy were assessed with a validated food frequency questionnaire. The outcomes were islet autoimmunity and type 1 diabetes. Cox proportional hazards regression analysis adjusted for energy, family history of diabetes, human leukocyte antigen (HLA) genotype and sex was used for statistical analyses. Total intake of vitamin C or iron from food and supplements was not associated with the risk of islet autoimmunity (vitamin C: HR 0.91: 95% CI (0.80, 1.03), iron: 0.98 (0.87, 1.10)) or type 1 diabetes (vitamin C: 1.01 (0.87, 1.17), iron: 0.92 (0.78, 1.08)), neither was the use of vitamin C or iron supplements associated with the outcomes. In conclusion, no association was found between maternal vitamin C or iron intake during pregnancy and the risk of islet autoimmunity or type 1 diabetes in the offspring.     

Determination of an Acceptable Portion Size of Daal for a Bangladeshi Community-Based Iron Intervention in Adolescent Girls: A Feasibility Study

Widely consumed daal (lentils) in Bangladesh are an ideal vehicle for iron (Fe) fortification; however, an acceptable portion size in meals needs to be determined to carry out a community feeding study in at-risk adolescent girls. A non-randomized crossover trial was conducted with n = 100 Bangladeshi girls (12.9 ± 2.0 years of age). Two recipes (thin and thick) and three portion sizes (25 g, 37.5 g, 50 g of raw lentil) of daal were served with 250 g of cooked white rice in a counter-balanced manner over 12 weeks. Each meal was fed to participants 5 days/week for two weeks. Ratings of hunger, satiety, and palatability were measured before and after each meal using Visual Analog Scales (VAS). The thick preparation in the 37.5 g portion (~200 g cooked) elicited higher VAS ratings of hunger, satiety, and palatability compared to all other meals. The 50 g portion of the thin preparation had VAS ratings similar to those of the 37.5 g thick preparation. Consuming the 37.5 g portion of fortified daal would provide 6.9 mg Fe/day to girls in a community-based effectiveness study. This would meet ~86% and ~46% of the Recommended Dietary Allowance (RDA) for Fe for girls aged 9–13 and 14–18 years, respectively.     

The IHAT-GUT Iron Supplementation Trial in Rural Gambia: Barriers,Facilitators, and Benefits

Introduction: In most sub-Saharan African countries iron deficiency anaemia remains highly prevalent in children and this has not changed in the last 25 years. Supplementation with iron hydroxide adipate tartrate (IHAT) was being investigated in anaemic children in a phase two clinical trial (termed IHAT-GUT), conducted at the Medical Research Council Unit the Gambia at the London School of Hygiene and Tropical Medicine (LSHTM) (abbreviated as MRCG hereof). This qualitative study aimed to explore the personal perceptions of the trial staff in relation to conducting a clinical trial in such settings in order to highlight the health system specific needs and strengths in the rural, resource-poor setting of the Upper River Region in the Gambia. Methods: Individual interviews (n = 17) were conducted with local trial staff of the IHAT-GUT trial. Data were analysed using inductive thematic analysis. Results: Potential barriers and facilitators to conducting this clinical trial were identified at the patient, staff, and trial management levels. Several challenges, such as the rural location and cultural context, were identified but noted as not being long-term inhibitors. Participants believed the facilitators and benefits outnumbered the barriers, and included the impact on education and healthcare, the ambitious and knowledgeable locally recruited staff, and the local partnership. Conclusions: While facilitators and barriers were identified to conducting this clinical trial in a rural, resource-poor setting, the overall impact was perceived as beneficial, and this study is a useful example of community involvement and partnership for further health improvement programs. To effectively implement a nutrition intervention, the local health systems and context must be carefully considered through qualitative research beforehand.     

Multiple Micronutrients,Including Zinc,Selenium and Iron,Are Positively Associated with Anemia in New Zealand Aged Care Residents

Anemia is a significant comorbidity for older adults not fully attributable to iron deficiency. Low-grade inflammation and other micronutrient deficiencies also contribute. This cross-sectional study examined the relationships between nutrient and non-nutrient factors with hemoglobin and anemia in 285 residents (>65 years) of 16 New Zealand aged-care facilities. Blood samples were analyzed for hemoglobin, ferritin, sTfR, hepcidin, zinc, selenium, and interleukin-6 (IL-6), (with ferritin, sTfR, zinc and selenium adjusted for inflammation). Linear regression models examined the relationships between micronutrient biomarkers (iron, zinc, selenium, vitamin B-12 and D), age, sex, and health factors with hemoglobin. Thirty-two percent of participants exhibited anemia, although <2% had either depleted iron stores or iron deficiency. Plasma zinc and selenium deficiencies were present in 72% and 38% of participants, respectively. Plasma zinc and total body iron (TBI) were positively associated (p < 0.05) with hemoglobin, while gastric acid suppressing medications, hepcidin, and interleukin-6 were inversely associated. These relationships were maintained after the application of anemia cut-offs. These findings emphasize the importance of considering multiple micronutrient deficiencies as risk factors for anemia.     

Zinc Nutritional Status in a Series of Children with Chronic Diseases: A Cross-Sectional Study

Background: Zinc is an essential trace element for the normal growth and development of human beings. The main objective was to evaluate the nutritional status of zinc and its association with nutritional indicators in a series of children with chronic diseases. Methods: The prevalence of patients with dietary zinc deficiency or deficit zinc intake (<80% DRI: dietary reference intake) was analyzed through prospective 72 h dietary surveys, and serum zinc deficiency or hypozincemia (≤70 µg/dL in children under 10 years of age in both sexes and in females older than 10 years and <74 μg/dL in males older than 10 years) was measured through atomic absorption spectrophotometry. The participants were classified according to their nutritional status by body mass index (BMI). Results: Mean serum zinc level in obese (87 µg/dL), undernourished (85 µg/dL), and eutrophic children (88 µg/dL) were normal, but in the undernutrition (60% DRI) and eutrophic (67% DRI) groups the mean dietary zinc intake was low compared to that in the obesity group (81% DRI). There were different associations between nutritional parameters, dietary zinc intake, and serum zinc. All patients with hypozincemia had dietary zinc deficiency. Conclusions: In the whole series, 69% of participants showed a zinc intake lower than recommended and might be at high risk of zinc deficiency.     

Postnatal Iron Supplementation with Ferrous Sulfate vs. Ferrous Bis-Glycinate Chelate: Effects on Iron Metabolism,Growth, and Central Nervous System Development in Sprague Dawley Rat Pups

Iron-fortified formulas and iron drops (both usually ferrous sulfate, FS) prevent early life iron deficiency, but may delay growth and adversely affect neurodevelopment by providing excess iron. We used a rat pup model to investigate iron status, growth, and development outcomes following daily iron supplementation (10 mg iron/kg body weight, representative of iron-fortified formula levels) with FS or an alternative, bioavailable form of iron, ferrous bis-glycinate chelate (FC). On postnatal day (PD) 2, sex-matched rat litters (n = 3 litters, 10 pups each) were randomly assigned to receive FS, FC, or vehicle control until PD 14. On PD 15, we evaluated systemic iron regulation and CNS mineral interactions and we interrogated iron loading outcomes in the hippocampus, in search of mechanisms by which iron may influence neurodevelopment. Body iron stores were elevated substantially in iron-supplemented pups. All pups gained weight normally, but brain size on PD 15 was dependent on iron source. This may have been associated with reduced hippocampal oxidative stress but was not associated with CNS mineral interactions, iron regulation, or myelination, as these were unchanged with iron supplementation. Additional studies are warranted to investigate iron form effects on neurodevelopment so that iron recommendations can be optimized for all infants.     

Multi-Nutrient Fortified Dairy-Based Drink Reduces Anaemia without Observed Adverse Effects on Gut Microbiota in Anaemic Malnourished Nigerian Toddlers: A Randomised Dose–Response Study

Prevalence of anaemia among Nigerian toddlers is reported to be high, and may cause significant morbidity, affects brain development and function, and results in weakness and fatigue. Although, iron fortification can reduce anaemia, yet the effect on gut microbiota is unclear. This open-label randomised study in anaemic malnourished Nigerian toddlers aimed to decrease anaemia without affecting pathogenic gut bacteria using a multi-nutrient fortified dairy-based drink. The test product was provided daily in different amounts (200, 400 or 600 mL, supplying 2.24, 4.48 and 6.72 mg of elemental iron, respectively) for 6 months. Haemoglobin, ferritin, and C-reactive protein concentrations were measured to determine anaemia, iron deficiency (ID) and iron deficiency anaemia (IDA) prevalence. Faecal samples were collected to analyse gut microbiota composition. All three dosages reduced anaemia prevalence, to 47%, 27% and 18%, respectively. ID and IDA prevalence was low and did not significantly decrease over time. Regarding gut microbiota, Enterobacteriaceae decreased over time without differences between groups, whereas Bifidobacteriaceae and pathogenic E. coli were not affected. In conclusion, the multi-nutrient fortified dairy-based drink reduced anaemia in a dose-dependent way, without stimulating intestinal potential pathogenic bacteria, and thus appears to be safe and effective in treating anaemia in Nigerian toddlers.     

High Prevalence of Stunting and Anaemia Is Associated with Multiple Micronutrient Deficiencies in School Children of Small-Scale Farmers from Chamwino and Kilosa Districts,Tanzania

Inadequate macro- and micronutrient nutrition and its consequences, such as anaemia, iron and vitamin deficiency, and growth retardation, could particularly affect children of small-scale farmers. In the present cross-sectional study, 666 school children aged 5–10 years from villages of Chamwino and Kilosa districts were studied for associations between nutritional and micronutrient status and dietary intake. The overall prevalence of stunting, underweight, and overweight was 28.1, 14.4, and 5%, while that of anaemia and deficiency of iron (ID), vitamin A (VAD), and zinc (ZnD) was 42.9, 29.3, 24.9, and 26.4%, respectively. Dietary recalls (24h) revealed that, except of iron (74%), only small proportions of children reached the recommended daily micronutrient intakes: 4% for zinc, 19% for vitamin A, and 14–46% for B vitamins. Stunting was highly associated with wasting in both districts and with VAD in Chamwino. Anaemia was predicted by ID, VAD, and ZnD in Chamwino and by elevated infection markers, C-reactive protein (CRP) and α-1 glycoprotein (AGP), in Kilosa. Overall, elevated CRP and/or AGP increased the risk while higher serum carotenoids indicating a diet of more fruit and vegetables reduced the risk of VAD. The significantly lower prevalence of anaemia and ID in Chamwino was related to higher iron and vitamin A intake and the consumption of mainly bulrush millet with dark green leafy vegetables compared to maize or rice with legumes in Kilosa. Nutrition and hygiene education integrated with home and school garden programmes could reduce the multiple burdens of anaemia; micronutrient deficiencies and infections; and, in the long term, the prevalence of stunting.