Experimental osteodystrophy of chronic renal failure induced by aluminum- and ferric-nitrilotriacetate in Wistar rats

The aluminum (Al) and iron (Fe) chelate complexes of nitrilotriacetate (NTA) cause renal insufficiency when they are administered intraperitoneally to rats. Their effects on bone metabolism were studied in 4 week old Wistar rats. Daily intraperitoneal administration of Al-NTA (3 mg Al/kg for 11 weeks) induced osteomalacia, impaired bone growth, decreased bone mineral density, lower serum PTH levels than normal as well as renal insufficiency. Al staining showed diffuse deposition in the trabecula and a strong linear band of aluminum deposited at the mineralization front and along the cement line. The osteoid seen markedly within the trabecula was probably the decalcified portion of the bone, the calcium apatite of which was defectively fabricated because of diffuse Al deposition in the trabecula. Al deposition along the cement line would make it much more susceptible to external shear stress than normal. Although daily intraperitoneal administration of Fe-NTA (6 mg Fe/kg for 11 weeks) caused impaired bone growth, decreased bone mineral content and renal insufficiency, the osteoid volume did not increase. Fe staining showed that Fe was deposited diffusely in the cytoplasm of osteoblasts. The results of this study demonstrated that during renal insufficiency, different minerals exhibi different modes of action on bone metabolism, and that AI-NTA is useful for experimental animal models of Al-induced osteomalacia in renal insufficiency.     

Cardiac Myxoma: Histochemical and Ultrastructural Localization of Glycosaminoglycans and Proteoglycans

A recurrent cardiac myxoma is examined histochemical ly at the ultrastructural level. By routine electron microscopy the stellate “myxoma” cell exhibits features suggestive of a secretory function in synthesis of its myxoid stroma. Spicer's high iron diamine (HID), which stains specifically for sulfated glycoconjugates, is utilized for intracellular localization of glycosaminoglycans. HID-positive reactive sites are localized within the Golgi-derived vacuoles and secretory granules of the myxoma cells. No staining is obtained with other cytoplasmic organelles except rare secondary lyso-somes. Although colloidal iron is less specific, both intracellular and extracellular positive reactive sites are observed. With ruthenium red staining the proteoglycans in the extracellular stroma can be visualized as numerous positively stained, polygonal 250-500 A matrix granules with faint filamentous projections. Positive intracellular ruthenium red-stained granules are also observed within the Golgi-derived vacuoles. The alcianophilia of the myxoid stroma with Alcian blue is almost completely abolished by prior treatment with bovine testicular hyaluronidase but is unaffected by leech hyaluronidase, indicating chondroitin sulfates A and/or C, not hyaluronic acid, as the major biochemical constituents of the stroma and the observed extracellular matrix granules. The above findings provide cytochemical evidence of intracellular synthesis of sulfated glycosaminoglycans and proteoglycans of the myxoma cell and its active participation in production of its stroma.     

Third trimester iron status and pregnancy outcome in non-anaemic women; pregnancy unfavourably affected by maternal iron excess

A prospective observational study was performed on 488 women with haemoglobin >/=10 g/dl at booking to examine the relationship between serum ferritin concentration quartiles at 28-30 weeks gestation with maternal characteristics, pregnancy complications and infant outcome. While there was no difference in the maternal characteristics or gestational age, the infant size decreased significantly and progressively from the lowest to the highest quartile. Despite a significant difference in the incidence of multiparous women, there was no difference in the incidence of most complications except for prelabour rupture of the membranes and infant admission to the neonatal unit. Compared with the other three quartiles, the highest quartile was associated with increased risk for preterm delivery and neonatal asphyxia, while the lowest quartile was associated with decreased risk of pre-eclampsia, prelabour rupture of the membranes, and infant admission to the neonatal unit. Overall, ferritin quartiles were correlated with other parameters of iron status and red cell indices, and ferritin concentration was inversely correlated with infant birthweight. Our findings suggested that maternal ferritin concentration is primarily a reflection of maternal iron status, and a high level is associated with unfavourable outcome. The rationale of routine iron supplementation in non-anaemic women needs to be re-examined.     

缺铁性贫血对学龄儿童某些认知能力影响的研究

本文采用双盲法对 IDA 和 NIDA学龄儿童各61名进行了认知能力测验及铁治疗前后的动态比较。结果表明:IDA 儿童识记再认、字母匹配反应时、数字扫描记忆和一般推理能力测验成绩较 NIDA 儿童差。经铁治疗的IDA 儿童,注意、短时记忆和心理动作反应速度均有明显提高。但对较高级认知能力的改善不明显。     

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