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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aluminium has recently been considered as a causative agent in dialysis encephalopathy, osteodystrophy, and anemia occuring in hemodialysis patients. The aim of this study is to prepare magnetic poly(2-hydroxyethylmethacrylate) (mPHEMA) adsorbent and to investigate it's useability for the removal of Al(III) ions from drinking and dialysis water. Magnetic PHEMA beads in a size range 80-120 microm were produced by a dispersion polymerization technique. Then Alizarin Red was covalenlty attached onto the mPHEMA beads. Al(III) adsorption from aqueous solutions was examined by batch system. mPHEMA beads were characterized by swelling tests, electron spin resonance (ESR), scanning electron microscopy (SEM), and elemental analysis. Important results obtained in this study are as follows: the swelling ratio of mPHEMA beads was 34%. The presence of magnetite in the polymeric structure was confirmed by ESR. The mPHEMA beads have a spherical shape and porous structure. Alizarin Red loading was 135.8 micromol g(-1) polymer. The maximum Al(III) adsorption was 722 micromol g(-1) polymer at pH 5.0. Non-specific Al(III) adsorption was about 23 micromol g(-1) polymer under the same conditions. High desorption ratios (98%) were achieved by using 0.1 M HNO3. It was possible to reuse the beads without significant loss of Al(III) adsorption capacity.
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PMID:Preparation of magnetic dye affinity adsorbent and its use in the removal of aluminium ions. 1185 78

The effect of asphyxia on iron metabolism and lipid peroxidation in newborn infants with hypoxic-ischemic encephalopathy (HIE) was investigated. Non-protein-bound iron (NPBI) and lipid peroxidation (thiobarbituric-acid-reactive species; TBARS) in plasma and hematological iron indices were measured in 15 healthy newborn infants (mean gestational age 39 04 weeks, SD 1); 15 asphyxiated infants without neurological abnormalities (AS-HIE; mean gestational age 38.8 weeks, SD 0.9); and 15 asphyxiated infants with neurological abnormalities (AS+HIE; mean gestational age 39.75 weeks, SD 1.4). Follow-up was performed at the age of 5 months. It was found that the detectable rates of NPBI in 10 of 15 of the AS-HIE group and 13 of 15 of the AS+HIE group were significantly higher than that of the control group (5 of 15; both p < 0.01). Plasma levels of TBARS in the control (9.20 micromol/L, SD 1.9) and AS-HIE infants (10.13 micromol/L, SD 2.7) were significantly lower than those of the AS+HIE group (13.42 micromol/L, SD 2.8). Serum iron, total iron binding capacity, and transferrin saturation in the AS+HIE group was higher than the corresponding values of the control and AS-HIE groups, although no statistical difference was found among them. At 5 months of age, all control and AS-HIE infants were neurologically normal, whether or not their NPBI was detectable. Of the 12 AS+HIE infants, four (all of whom had detectable NPBI) were neurologically impaired. The average Gross Development Quotient of AS+HIE infants was significantly lower than that of the control or AS-HIE groups (p < 0.01). Results showed that asphyxia could affect iron metabolism and lead to a significant increase in NPBI and lipid peroxidation in newborn infants with HIE, indicating that iron delocalization induced by asphyxia plays a role in the brain injury of asphyxiated infants.
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PMID:Effect of asphyxia on non-protein-bound iron and lipid peroxidation in newborn infants. 1254 51

Among various hypothetical mechanisms for the in vivo production of reactive oxygen species, transition metal-catalyzed reactions in cooperation with a biologic reducing agent like ascorbic acid or superoxide may be some of the most important. In the present study, we retrospectively examined the existence of non-protein-bound metal ions, an essentially hazardous pro-oxidant form of various transition metals, and the occurrence of metal-catalyzed reactive oxygen species production in cerebrospinal fluid (CSF) of 10 infants with hypoxic ischemic encephalopathy (HIE) subsequent to perinatal asphyxia and 12 control infants within 72 h of birth. Non-protein-bound iron was detected in eight out of 10 CSF samples from the HIE infants and its level was significantly correlated with Sarnat's clinical stage, whereas none of the control infants had detectable non-protein-bound iron levels. Non-protein-bound copper was below the detection limit in all CSF samples from both groups. Ascorbic acid was significantly increased in the CSF of HIE infants when compared with that of controls (means, 664.9 versus 449.4 microM, p = 0.008). ortho-Tyrosine and meta-tyrosine, which are highly specific and sensitive markers of protein oxidation induced by hydroxyl radicals, were significantly higher in HIE infants than in controls when evaluated by the ratio relative to their source amino acid, phenylalanine [means, 110.5 versus 75.4, p = 0.018 for ortho-tyrosine/phenylalanine; 104.6 versus 67.7 (nM/microM x 10(2)), p = 0.048 for meta-tyrosine/phenylalanine]. Both ratios were significantly correlated with non-protein-bound iron, but not with ascorbic acid. Our preliminary observations provide direct evidence that hydroxyl radicals are generated in the CNS during asphyxiation. Iron chelation therapy could be worth developing as a neuroprotective strategy for perinatal asphyxia.
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PMID:Non-protein-bound transition metals and hydroxyl radical generation in cerebrospinal fluid of newborn infants with hypoxic ischemic encephalopathy. 1261 9

The trace metal copper is an essential cofactor for a number of biological processes, including mitochondrial oxidative phosphorylation, free-radical eradication, neurotransmitter synthesis and maturation, and iron metabolism. Consequently, copper transport at the cell surface and the delivery of copper to intracellular proteins are critical events in normal cellular homeostasis. Four genes have been reported to influence the cellular uptake and the delivery of copper to specific cell compartments and proteins. These include hCTR1, which regulates cellular copper uptake; HAH1, which mediates the transfer of copper to the Menkes and Wilson disease transporters; CCS, which is related to the transfer of copper to superoxide dismutase; and hCOX17, which directs trafficking of copper to mitochondrial cytochrome-c oxidase. At present, no genetic disorders have been associated with defects in these four copper transporter genes. In this study, we test the possibility that defective copper uptake or intracellular translocation represents the basic defect in three categories of candidate phenotypes among 22 patients: ethylmalonic encephalopathy; mitochondriopathies of unknown aetiology; and neurodevelopmental abnormalities with clinical and chemical evidence of copper deficiency. Mutation analyses of the copper uptake protein, hCTR1, and the three copper chaperones were performed by direct sequencing of the whole coding regions. No causative mutations were identified for the four copper transporter genes in 22 patients. A heterozygous polymorphism (847G>A) for CCS was detected in 7 patients. For the distinct disease entity ethylmalonic encephalopathy, we additionally show normal mRNA levels for each of the four genes. The negative results notwithstanding, we encourage ongoing study of additional patients with candidate phenotypes. Further, our results are consistent with the notion that other unknown copper-related transporters could be involved in diseases.
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PMID:Mutation analysis of copper transporter genes in patients with ethylmalonic encephalopathy, mitochondriopathies and copper deficiency phenotypes. 1287 41

Phosphate (Pi) retention is a common problem in patients with chronic kidney disease, particularly in those who have reached end-stage renal disease (ESRD). In addition to causing secondary hyperparathyroidism and renal osteodystrophy, recent evidence suggests that, in ESRD patients, high serum phosphorus concentration and increased calcium and phosphorous (Ca x P) product are associated with vascular and cardiac calcifications and increased mortality. Dietary phosphorus restriction and Pi removal by dialysis are not sufficient to restore Pi homeostasis. Reduction of intestinal Pi absorption with the use of Pi binders is currently the primary treatment for Pi retention in patients with ESRD. The use of large doses of calcium-containing Pi binders along with calcitriol administration may contribute to over-suppression of parathyroid hormone secretion and adynamic bone disease as well as to a high incidence of vascular calcifications. When used in patients with impaired renal function, aluminium salts were found to accumulate in bone and other tissues, resulting in osteomalacia and encephalopathy.Sevelamer, an aluminium- and calcium-free Pi binder can reduce serum phosphorus concentration and is associated with a significantly lower incidence of hypercalcaemia, while maintaining the ability to suppress parathyroid hormone production. An additional benefit of sevelamer is its ability to lower low density lipoprotein-cholesterol and total cholesterol levels. Sevelamer attenuates the progression of vascular calcifications in haemodialysis patients, which may lead to lower mortality. The use of sevelamer in non-dialysed patients might aggravate metabolic acidosis, common in these patients. Several other calcium-free Pi binders are in development. Lanthanum carbonate has shown significant promise in clinical trials in ESRD patients. Magnesium salts do not offer a significant advantage over currently available Pi binders. Their use is restricted to patients receiving dialysis since excess magnesium must be removed by dialysis. Iron-based compounds have shown variable efficacy in short-term clinical trials in small numbers of haemodialysis patients. Mixed metal hydroxyl carbonate compounds have shown efficacy in animals but have not been studied in humans. Major safety issues include absorption of the metal component with possible tissue accumulation and toxicity.
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PMID:Safety of new phosphate binders for chronic renal failure. 1464 Jul 73

BACKGROUND: Aluminum has recently been recognized as a causative agent in dialysis encephalopathy, osteodystrophy, and microcytic anemia occurring in patients with chronic renal failure who undergo long-term hemodialysis. Only a small amount of Al(III) in dialysis solutions may give rise to these disorders. METHODS: Magnetic poly(2-hydroxyethyl methacrylate) (mPHEMA) beads in the size range of 80-120 microm were produced by free radical co-polymerization of HEMA and ethylene dimethacrylate (EDMA) in the presence of magnetite particles (Fe3O4). Then, metal complexing ligand alizarin yellow was covalently attached onto mPHEMA beads. Alizarin yellow loading was 208 micromol/g. These beads were used for the removal of Al(III) ions from tap and dialysis water in a magnetically stabilized fluidized bed. RESULTS: Al(III) adsorption capacity of the beads decreased with an increase in the flow-rate. The maximum Al(III) adsorption was observed at pH 5.0. Comparison of batch and magnetically stabilized fluidized bed (MSFB) maximum capacities determined using Langmuir isotherms showed that dynamic capacity (17.5 mg/g) was somewhat higher than the batch capacity (11.8 mg/g). The dissociation constants for Al(III) were determined using the Langmuir isotherm equation to be 27.3 mM (MSFB) and 6.7 mM (batch system), indicating medium affinity, which was typical for pseudospecific affinity ligands. Al(III) ions could be repeatedly adsorbed and desorbed with these beads without noticeable loss in their Al(III) adsorption capacity. CONCLUSIONS: Adsorption of Al(III) demonstrate the affinity of magnetic dye-affinity beads. The MSFB experiments allowed us to conclude that this inexpensive sorbent system may be an important alternative to the existing adsorbents in the removal of aluminium.
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PMID:Performance of dye-affinity beads for aluminium removal in magnetically stabilized fluidized bed. 1532 49

Alexander disease is a fatal neurodegenerative disorder resulting from missense mutations of the intermediate filament protein, GFAP. The pathological hallmark of this disease is the formation of cytoplasmic protein aggregates within astrocytes known as Rosenthal fibers. Transgenic mice engineered to over-express wild-type human GFAP develop an encephalopathy with identical aggregates, suggesting that elevated levels of GFAP in addition to mutant protein contribute to the pathogenesis of this disorder. To study further the effects of elevated GFAP and Rosenthal fibers per se, independent of mutations, we performed gene expression analysis on olfactory bulbs of transgenic mice at two different ages to follow the progression of pathology. The expression profiles reveal a stress response that includes genes involved in glutathione metabolism, peroxide detoxification and iron homeostasis. Many of these genes are regulated by the transcription factor Nfe2l2, which is also increased in expression at 3 weeks. An immune-related response occurs with activation of cytokine and cytokine receptor genes, complement components and acute phase response genes. These transcripts are further elevated with age, with additional induction of macrophage-specific markers such as Mac1 and CD68, suggesting activation of microglia. At 4 months, decreased expression of genes for microtubule-associated proteins, vesicular trafficking proteins and neurotransmitter receptors becomes apparent. Interneuron-specific transcription factors including Dlx family members and Pax6 are downregulated as well as Gad1 and Gad2, suggesting impairment of GABAergic granule cells. Together, these data implicate an initial stress response by astrocytes, which results in the activation of microglia and compromised neuronal function.
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PMID:Gene expression analysis in mice with elevated glial fibrillary acidic protein and Rosenthal fibers reveals a stress response followed by glial activation and neuronal dysfunction. 1601 34

Aluminum is environmentally abundant, but not an essential element. Aluminum has been associated with several neurodegenerative diseases, such as dialysis encephalopathy, amyotrophic lateral sclerosis and Parkinsonism dementia in the Kii peninsula and Guam, and in particular, Alzheimer's disease. Although this association remains controversial, there is increasing evidence which suggests the implication of metal homeostasis in the pathogenesis of Alzheimer's disease. Aluminum, zinc, copper, and iron cause the conformational changes of Alzheimer's amyloid-beta protein. Al causes the accumulation of tau protein and amyloid-beta protein in experimental animals. Aluminum induces neuronal apoptosis in vivo as well as in vitro. Furthermore, a relationship between aluminum and the iron-homeostasis or calcium-homeostasis has been suggested. Based on these findings, the characteristics of aluminum neurotoxicity are reviewed, and the potential link between aluminum and neurodegenerative diseases is reconsidered.
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PMID:Effects of aluminum on the nervous system and its possible link with neurodegenerative diseases. 1630 86

Infants and children may undergo severe oxidative stress due to disease state, pre-existing nutritional status, frequent use of oxygen, and lower levels of antioxidant defenses. Antioxidant defenses, made up of intracellular and extra-cellular components, work synergistically to prevent oxidative damage. Total antioxidant activity (TAA) was analyzed by method of ferric reducing antioxidant power assay (FRAP). Patients admitted in Pediatric Dept, RNT Medical College, Udaipur, India were selected for these studies. TAA level in neonates with hypoxic-ischemic-encephalopathy (HIE) stage III and in poor outcome cases was significantly low. Erythrocyte SOD activity level was low in pre-term neonates. TAA level in severely malnourished children at the time of hospital admission was low. This low antioxidant level in severely malnourished children could be multi-factorial viz. low zinc, selenium, vitamin A & C deficiency, recurrent infections, elevated free iron and chronic starvation stage. Delayed recovery of oxidant injury may lead to delayed incomplete recovery at cellular level. In a study of 29 tuberculosis patients TAA level was found to be low in tubercular patients compared with control. TAA level decreased more in CNS tuberculosis compared with other system tuberculosis. In a study of nutritional tremor syndrome TAA, ascorbic acid and alpha-tocopherol levels were low during pre-tremor phase compared with tremor phase (ATS). Pre-term neonates have incompletely developed antioxidant defenses and are deficient in vitamin E, which is normally derived from maternal circulation at the end of 3rd trimester. Therefore, decreased TAA level in HIE with poor outcome indicates addition of antioxidants in therapeutic strategy. Since rise in TAA in antioxidant supplemented group of severely malnutrition children was higher with good outcome compared with nonsupplemented group it would be prudent to supplement antioxidant during nutritional management. These studies have shown that health benefits can be obtained by children with a reduced risk of disease from supplements of antioxidant nutrients. The amounts of optimal supplements in these disorders, whether pharmacologic or large, are to be determined. Further work is needed to show whether modest increases in nutrient intakes in children with these disorders will delay or prevent the complications and improve the outcome. Therefore, available evidence regarding health benefits to be achieved by supplementing antioxidant nutrients is encouraging. Free radical injury and antioxidant deficiency is more common than what we think. Severely malnourished children and children suffering from chronic infections and diseases are at several fold increased risk of antioxidant deficiency and likely to suffer from free radical injury. Appropriate interventions are required in reducing the risk associated with these observations.
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PMID:Free radicals: emerging challenge in environmental health research in childhood and neonatal disorders. 1696 76

Inflammatory leukocytes infiltrate the CNS parenchyma in neuroinflammation. This involves cellular migration across various structures associated with the blood-brain barrier: the vascular endothelium, the glia limitans, and the perivascular space between them. Leukocytes accumulate spontaneously in the perivascular space in brains of transgenic (Tg) mice that overexpress CCL2 under control of a CNS-specific promoter. The Tg mice show no clinical symptoms, even though leukocytes have crossed the endothelial basement membrane. Pertussis toxin (PTx) given i.p. induced encephalopathy and weight loss in Tg mice. We used flow cytometry, ultra-small superparamagnetic iron oxide-enhanced magnetic resonance imaging, and immunofluorescent staining to show that encephalopathy involved leukocyte migration across the glia limitans into the brain parenchyma, identifying this as the critical step in inducing clinical symptoms. Metalloproteinase (MPs) enzymes are implicated in leukocyte infiltration in neuroinflammation. Unmanipulated Tg mice had elevated expression of tissue inhibitor of metalloproteinase-1, matrix metalloproteinase (MMP)-10, and -12 mRNA in the brain. PTx further induced expression of tissue inhibitor of metalloproteinase-1, metalloproteinase disintegrins-12, MMP-8, and -10 in brains of Tg mice. Levels of the microglial-associated MP MMP-15 were not affected in control or PTx-treated Tg mice. PTx also up-regulated expression of proinflammatory cytokines IL-1beta and TNF-alpha mRNA in Tg CNS. Weight loss and parenchymal infiltration, but not perivascular accumulation, were significantly inhibited by the broad-spectrum MP inhibitor BB-94/Batimastat. Our finding that MPs mediate PTx-induced parenchymal infiltration to the chemokine-overexpressing CNS has relevance for the pathogenesis of human diseases involving CNS inflammation, such as multiple sclerosis.
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PMID:Metalloproteinases control brain inflammation induced by pertussis toxin in mice overexpressing the chemokine CCL2 in the central nervous system. 1708 42


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