儿童铁缺乏对血清IgG亚类及PnPs特异性IgG亚类抗体的影响

本文测定铁缺乏症患儿血清IgG亚类(47例)和PnPs特异性IgG_1、IgG_2抗体(18例)。发现47例缺铁儿童中28例伴IgG亚类缺陷,各亚类缺陷检出率依次为:IgG_4 27.66％(13/47)、IgG_1 21.28％(10/47)、IgG_2 14.89％(7/47)、IgG_2 2.13％(1/47)。与同龄正常儿童比较,缺铁组血清IgG_4和IgG_1均值以及PnPs特异性IgG_1、IgG_2抗体水平明显降低;缺铁患儿外周血CD~+_4细胞百分率及CD~+_4/CD~+_8细胞比值降低,IL-6活性、T淋巴细胞增殖反应减低。缺铁时反复呼吸道感染率(占63.83％)亦明显增高。提示缺铁不仅致T细胞功能受损,B细胞功能亦明显障碍。     

Extra- and intracellular free iron and the carotid body responses

The hypothesis that chelation of free iron, by decreasing reactive oxygen species (ROS), might mimic hypoxia and stimulate the carotid body was tested. We used the iron chelators, desferrioxamine (DFO, 200-400 microM) initially, and later ciclopirox olamine (CPX, 2.5-5.0 microM), on rat carotid body in vitro and measured chemosensory activity and [Ca2+]i in isolated cultured glomus cell clusters during normoxia and hypoxia. Although acute treatment of DFO might not penetrate the cell, and extracellular DFO would not influence these activities whereas CPX significantly increased chemosensory activities as well as increased [Ca2+]i in normoxia. We concluded that chelation of extracellular free iron did not alter ROS formation and oxygen sensing. Chelation of intracellular free iron and, therefore, a decrease in intracellular ROS appears to influence oxygen sensing in the carotid body.     

Central nervous system inflammatory response after cerebral infarction as detected by magnetic resonance imaging

Brain inflammation contributes to the tissue injury caused by ischemic stroke. Macrophages as the most abundant inflammatory cell population in stroke lesions can be visualized using ultrasmall superparamagnetic iron oxide (USPIO) as a cell-specific contrast agent for magnetic resonance imaging (MRI). The aim of our present study was to delineate the inflammatory response during experimental cerebral infarction by means of USPIO-enhanced MRI and to correlate the spatial distribution of USPIO-induced MR signal alterations with cellular infiltration and iron deposition. To this end USPIOs were administered to Wistar rats 5 days after photothrombotic cerebral infarction. MR imaging at 7 T performed 24 h later displayed a rim-like signal loss around the infarction in the USPIO treated animals. On histological brain sections obtained from the same animals after MRI the distribution of iron and ED1+ phagocytes was in full spatial agreement with the signal loss seen on T2*-weighted images. Our study validates USPIO-enhanced MRI as an important tool for the noninvasive visualization of brain inflammation in stroke and other CNS pathologies.     

The Lipofuscin-Iron Association in Pigmentosis Tubae

Pigmentosis tubae (PT) is a rare condition characterized by the presence of numerous lipofuscin-laden macrophages in the lamina propria of the fallopian tube. Two women, who also had endometriotic ovarian cysts, showed polypoid pigmented tubal mucosae. In addition to lipofuscin, occasional cells showed spotty positivity for iron. Ultrastructural examination of the tubal mucosa showed the lipofuscin-containing bodies, which were similar to lipofuscin-containing lysosomes found in other pigmented conditions. Cytoplasmatic ferritin and hemosiderin in siderosomes were observed in macrophages and endothelial cells of the lamina propria. The present study is the first to demonstrate the presence of iron-containing particles and lipofuscin in the residual bodies of PT. The origin of the excess iron is not clear, but erythrophagocytosis and an abnormal tubal environment could play a role. Iron-promoted lipid peroxidation may alter the lysosomal membranes and contribute to the excessive accumulation of lipofuscin in these cells.     

Copper and iron-induced oxidative damage in non-tumor bearing LEC rats

The copper and Iron status in the liver of non-tumor bearing Long-Evans Cinnamon (LEC) rats (average age 17 months) was investigated. A direct quantitation of loosely-bound copper and iron was also investigated by using a chelating agent, nitrilotriacetic acid (NTA-chelatable free copper and iron). Besides the total copper and iron contents, the level of NTA-chelatable free copper was also higher in LEC rats than In LEA rats (P<0.05). But for the free iron level there was no signiflcant difference between the two rat groups (P>0.05). The formation of thiobarbituric acid-reactive substances was higher In LEC rats than In LEA rats (P<0.01). The 4–hydroxy-2–nonenal (HNE)-modified proteins were also clearly demonstrated in LEC rat liver. The copper and iron which produced the most important effect In the process of oxidative damage in LEC rats could not be distinguished. Even though free copper, which could induce free radical injuries, was increased in LEC rats, neither tumor-induction nor preneo-plastic lesions in the experimental LEC rats were observed. Therefore it is speculated that the elevation of a free iron is another important factor. Copper and iron, both important translation metals In the body, may participate In the Induction of DNA damage and oncogenesls     

Biological functions of ceruloplasmin and their deficiency caused by mutation in genes regulating copper and iron metabolism

Ceruloplasmin, a multicopper ferroxidase, is involved in iron and copper homeostasis and integrates these metabolic pathways. Impaired biosynthesis of ceruloplasmin caused by gene mutations disturbs iron metabolism with iron deposition in different organs, especially in the basal ganglia, and severe neuronal damage. Dysfunction of ATP7B, a copper-transporting ATPase leads to the development of Wilson’s disease,i.e., multiple abnormalities in copper metabolism associated with reduced synthesis of holoceruloplasmin and biliary copper excretion controlled by both proteins. The lowest content of serum ceruloplasmin is observed in the most grave early neurological form of Wilson’s disease (according to N. V. Konovalov’s classification), which confirms the important role of ceruloplasmin in the striatal metabolism of catecholamines. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 130, No. 8, pp. 124–133, August, 2000     

Iron down-regulates macrophage anti-tumour activity by blocking nitric oxide production

Although the inhibitory effect of iron on macrophage production of tumoricidal free radical nitric oxide (NO) has been reported, its possible influence on macrophage anti-tumour activity has not been established. In the present study, FeSO4 markedly reduced IFN-gamma + LPS-induced NO synthesis in mouse and rat macrophages. The effect of iron coincided with the loss of macrophage cytotoxic activity against NO-sensitive C6 rat astrocytoma and L929 mouse fibrosarcoma cell lines, as measured by MTT assay for cellular respiration and the crystal violet test for cell viability. Tumour cell survival did not improve further in the presence of FeSO4 if macrophage NO release and cytotoxicity were already blocked by aminoguanidine. In accordance with the results obtained with exogenous iron, cell membrane permeable iron chelator o-phenanthroline enhanced both macrophage NO release and anti-tumour activity. Iron also down-regulated NO production and increased the viability of L929 fibrosarcoma cells stimulated with IFN-gamma + LPS in the absence of macrophages. However, neither NO release nor cell viability was affected by iron addition to cultures of the C6 astrocytoma cell line. Iron was unable to prevent L929 and C6 cell death induced by the NO releasing chemicals SNP and SIN-1, indicating that iron-mediated inhibition of NO synthesis, rather than interference with its cytotoxic action, was responsible for the protection of tumour cells. Collectively, these results indicate that iron might protect tumour cells by reducing both macrophage and tumour cell-derived NO release.     

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.     

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.