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

Evidence of a link between aluminium and Alzheimer's disease, parkinsonism-dementia of Guam, and dialysis encephalopathy raises questions regarding the role of this element in the pathogenesis of these conditions. Therefore, we have investigated the use of gallium-67 (67Ga) as a marker for brain uptake of aluminium. The binding of 67Ga to plasma proteins has been studied, and the blood-brain barrier permeability and autoradiographic distribution of this isotope in rat brain determined in vivo. The autoradiographic distribution of 125I-Fe-transferrin receptors in rat brain has also been determined in vitro. Results show that 67Ga was bound to plasma transferrin, entered the brain with a blood-brain barrier permeability of 2.48 x 10(-6) ml/min/g, and showed a marked regional distribution that was very similar to that of 125I-Fe-transferrin receptors. Our data suggest that the vulnerability of the hippocampus, amygdala, and cerebral cortex in conditions such as those mentioned above may be partly due to an increased uptake and deposition of aluminium in these regions by the iron transport system.
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PMID:Gallium-67 as a potential marker for aluminium transport in rat brain: implications for Alzheimer's disease. 235 20

Recent studies have emphasised the potential neurotoxicity of aluminium in dialysis encephalopathy and it has also been suggested that this element may have a role in the pathogenesis of Alzheimer's disease. Aluminium is known to be transported by the iron transport protein transferrin. In this study using receptor autoradiography we have demonstrated the presence of transferrin binding sites in the human forebrain and shown a pattern similar to that found in other species. Imaging secondary ion mass spectrometry has demonstrated the distribution of aluminium-containing cell-like profiles in the brains of chronic renal dialysis patients who have raised levels of brain aluminium (greater than 4 micrograms/g dry weight) and even in dialysis patients where the gross level of aluminium was within the normal range. The density of these profiles corresponded to the regions of high transferrin receptor density. In contrast, the distribution of iron in the brain showed an inverse correlation with transferrin receptor density with highest iron levels present in the globus pallidus, an area of low transferrin receptor density. These results suggest that the regional distribution of neuropathological changes seen in dialysis encephalopathy patients and also Alzheimer's disease may reflect the distribution of transferrin receptors. The discrepancy between iron distribution and transferrin receptor distribution suggests that further, as yet uncharacterized mechanisms, govern the distribution of brain iron.
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PMID:Comparison of the regional distribution of transferrin receptors and aluminium in the forebrain of chronic renal dialysis patients. 261 72

Reye's syndrome is an acute hepatopathy and encephalopathy affecting children during the convalescent period of a viral infection, frequently influenza B. The role of influenza B in the pathogenesis of Reye's syndrome is unknown. To investigate this relationship, an in vitro system was designed to examine the interaction of influenza B virus with a cell line of human hepatocytes (HepG2) which retains many specific hepatic synthetic characteristics. HepG2 was capable of supporting a productive infection by influenza B, although greater virus inputs were required than in fully permissive Madin-Darby canine kidney cells. Because of the recent association of Reye's syndrome with aspirin use, the kinetics of influenza B growth were studied in the presence of acetylsalicylic acid (25 and 100 micrograms/ml) and were not found to be altered. Protein synthesis by HepG2 cells was decreased by 80% in influenza B-infected cells when compared to uninfected controls. Acetylsalicylic acid, 100 micrograms/ml, did not affect the rate of 35S-methionine incorporation by infected or uninfected HepG2 cells. The rates of synthesis of specific proteins (albumin, transferrin, and apoprotein B) by HepG2 cells were determined by immunoprecipitation of 35S-methionine labeled cell lysates. After 12 h of infection, synthesis of all three plasma proteins was decreased by 40-60%. These studies describe a useful system for delineation of mechanisms by which influenza B virus interacts with host hepatocytes and the host-cell protein synthetic machinery. The studies could be pertinent to the pathogenesis of Reye's syndrome.
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PMID:Protein synthesis by HepG2 cells infected with influenza B virus. 283 18

Between March 1982 and September 1983, 40 inpatients (25 men and 15 women, mean age 53 years) with alcoholic cirrhosis and total serum bilirubin greater than or equal to 5 mg per dl were studied. Those with hepatocellular carcinoma, renal failure, hyponatremia, septicemia, spontaneous bacterial peritonitis, gastrointestinal bleeding, and hepatic coma were excluded. Patients were studied for 28 days. The two groups were offered an oral diet containing 40 kcal per kg per day. Patients in the supplementary parenteral nutrition group received 40 kcal per kg per day and 200 mg nitrogen per kg per day using a central catheter. The major endpoint was total serum bilirubin on Day 28. On admission, serum bilirubin was not significantly different in the two groups: oral group, 12.5 +/- 6.6 mg per dl; supplementary parenteral nutrition group, 12.3 +/- 8.5 mg per dl. On Day 28, serum bilirubin was lower in the supplementary parenteral nutrition group (2.5 +/- 1.4 mg per dl) than in the oral group (4.1 +/- 2.2 mg per dl) (p less than 0.02). Serum bilirubin was also lower in the supplementary parenteral nutrition group than in the oral group on Days 7, 14 and 21 (p less than 0.05). Analysis of covariance, considering serum bilirubin on admission and at randomization and time between admission and randomization, confirmed these results. On Day 28, anthropometric parameters, serum transferrin, prealbumin and retinol-binding protein were higher in the supplementary parenteral nutrition group, but the differences were not significant. Serum albumin was significantly lower in the supplementary parenteral nutrition group. The incidence of encephalopathy and sepsis was not significantly different between the two groups.
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PMID:A randomized clinical trial of supplementary parenteral nutrition in jaundiced alcoholic cirrhotic patients. 308 33

The effects of branched chain amino acid (BCAA)-enriched diets (fed for 7 days) on encephalopathy, plasma amino acid concentrations, aromatic amino acid turnover, and protein synthesis rates were determined in eight patients with alcoholic liver failure. Four patients were given the diet intravenously (iv group) (total amino acids, 60-80 g/day, BCAA content 51%, energy 2000 kcal/day) and four patients (NG group) were given a semi-elemental formulation via constant nasogastric (NG) infusion (amino acids 58 g, BCAA 43%, oligopeptides 19.5 g, energy 2000 kcal/day). The enteral diet was given at one-half strength for the first 3 days. A 10-hr constant infusion of [U-14C]phenylalanine tracer was used in four patients to measure aromatic amino acid (AA) turnover and rates of incorporation into various body proteins. Seven of the eight patients made a good clinical recovery, with reversal of encephalopathy within 3 days of dietary intervention. One became septicemic and deteriorated. While plasma bilirubin concentrations dropped, liver enzymes remained elevated. Mean nitrogen balance was negative at the beginning and positive at the end of the study, in both groups. Initial amino acid profiles demonstrated low plasma BCAA content and BCAA:AA ratios. Significant improvements occurred in the iv group by day 2 and in both groups by day 7. Isotope studies showed that, whereas aromatic amino acid oxidation remained unchanged, greater quantities were incorporated in whole body protein, albumin, transferrin, fibrinogen, and immunoglobulins.
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PMID:Enteral and parenteral branched chain amino acid-supplemented nutritional support in patients with encephalopathy due to alcoholic liver disease. 311 90

We performed a controlled trial of peripheral hyperalimentation in moderate and severe alcoholic hepatitis to determine whether improvement in survival and liver function could be obtained. Twelve patients with moderate and 22 with severe alcoholic hepatitis were randomized to 28 days of peripheral parenteral nutrition (PPN) or standard therapy (ST). In the moderate group, six were treated with each therapy. In the severe group, 10 were treated with PPN and 12 with ST. Routine liver tests, hepatocyte function (galactose elimination capacity), estimated hepatic blood flow (galactose clearance) and assessment of ascites and encephalopathy were performed at randomization and at 28 days. Groups were equally matched at randomization. In the moderate group PPN produced no improvement in morbidity (liver tests) and mortality (no deaths). In the severe group there were seven deaths (4 PPN, 3 ST). PPN produced greater improvement than ST in serum bilirubin and transferrin concentrations and a trend toward greater improvement in prothrombin time, serum albumin and galactose elimination capacity. PPN had no deleterious effect on encephalopathy or ascites as only ST patients developed ascites or encephalopathy after randomization. We conclude that PPN compared to ST (1) provides no benefit in moderate alcoholic hepatitis, but (2) did more rapidly improve morbidity (liver tests) and probably liver function in severe alcoholic hepatitis; (3) PPN did not improve early mortality, and (4) it had no deleterious effect on encephalopathy or ascites.
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PMID:A randomized controlled study of peripheral parenteral nutrition in moderate and severe alcoholic hepatitis. 314 49

One hundred and thirty-one patients underwent clinical and biological investigation with the following determinations performed on the same day; presence or absence of ascites, icterus and/or encephalopathy, coagulation study, biochemical determinations including albumin, transferrin and immunoglobulins immunoassays. The principal component analysis of biological data showed two sets of highly representative and inversely correlated data; one included coagulation tests, albumin and transferrin, and the other included immunoglobulin A/transferrin ratio, immunoglobulin A and total bilirubin. Clinical and biological data were computed using discriminant analysis between dead and survivors. Six parameters were then selected (total bilirubin, encephalopathy, factor V, AST, antithrombin III and transferrin) giving a correct prognosis in 81.6% (31/38) of cases in a test sample. Neither ascites nor immunoglobulins were useful for the estimation of the prognosis.
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PMID:Multivariate analysis of clinical and biological data in cirrhotic patients: application to prognosis. 679 41

In order that better therapeutic approaches to disorders in man characterized by aluminium (Al) overload might be developed it is essential to have an appropriate animal model. Chronic oral administration of Al citrate to male Wistar rats leads to an Al overload in a relatively short period of time when compared to previous published animal models. Liver and brain Al levels are increased by 25 and 30-fold respectively compared to control rats after 6 months of loading. Al tissue content was significantly greater when the Al citrate was administered in an iron-free diet. The distribution of Al in brain was similar to that in the Al encephalopathy of patients with chronic renal failure or Alzheimer's disease and is in accord with observations that areas of brain that accumulate greatest amounts of Al have highest concentrations of transferrin receptors. In the brain, the toxic effect of Al at the cellular level was characterized by an extensive cytoplasmic vacuolation in astrocytes (especially) and neurones. These changes are reminiscent of those observed in certain human neurodegenerative diseases.
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PMID:An experimental animal model of aluminium overload. 784 2

Aluminum (Al) accumulation in renal failure patients can result in encephalopathy, osteomalacia, and anemia. Since the cellular mechanisms of Al toxicity are not completely understood we used cultured Friend erythroleukemia cells (FEC) as a model system of Al-induced anemia. In this system Al accumulation leads to decreased cell growth and hemoglobin synthesis despite increased iron (Fe) uptake by transferrin (Tf) endocytosis. In FEC we evaluated the effect of Al on the cellular and subcellular accumulation of Fe, ferritin concentration, the uptake of Fe by ferritin, the exit of cellular Fe, and membrane lipid peroxidation. FEC were grown in media with or without the addition of Al-Tf and studies were done at 24, 48, 72, and 96 hours after plating. The highest concentration of intracellular Al was found in mitochondria with lesser amounts in the nucleus, and the least was in cytosol. The rate of Fe uptake was higher in Al-loaded FEC without a proportionally increased rate of exit. This resulted in higher concentrations of Fe in Al-loaded FEC. Subcellular fractionation following the uptake of 59Fe, 125I-Tf in Al-loaded FEC showed increased uptake of 59Fe in the nuclear and mitochondrial compartments with no increase in the cytosol. Al-loaded FEC showed decreased ferritin content and decreased uptake of 59Fe by ferritin. Increased membrane lipid peroxidation occurred in Al-loaded FEC at 96 hours as assessed by cellular malonyldialdehyde accumulation. These results indicate that Al disrupts Fe metabolism in FEC by increasing cellular Fe content with increased compartmentalization of Fe in the mitochondria and nuclei, decreased ferritin content, and decreased uptake of Fe by ferritin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Aluminum alters the compartmentalization of iron in Friend erythroleukemia cells. 819 64

Some recent proposals in management of alcoholic liver disease are discussed focusing on early diagnosis and treatment of alcohol abuse itself, alcoholic hepatitis early mortality, clinical meaning of nutritional therapy, serological approach and treatment of hepatic fibrosis, and problems in liver transplantation for end stage alcoholic liver cirrhosis. CAGE or similar systematized brief questionnaires, and desialylated transferrin/total transferrin ratio as serological marker, seems to be interesting contributions to "hidden" alcohol abuse diagnosis and abstinence control while psycho-social support and voluntary incorporation to self-aid groups are the best weapons to reach persistent abstinence. Corticosteroids seems to improve survival in a selected group of patients with severe alcoholic hepatitis, specially in those presenting encephalopathy but free of GI bleeding, decompensated diabetes, active infections, pancreatitis, and other contraindications or adverse effects of these drugs. Relationship between direct toxicity and nutritional deficiencies in pathogenesis of alcoholic liver injury are not clear enough, but malnutrition is generally present in patients requiring hospitalization, and related to clinical severity; oral, enteral or parenteral nutritional supplementation in this order of preference according to patients condition, associated or not with steroid anabolics, are useful in cases with moderate to severe alcoholic hepatitis or decompensated cirrhosis to eliminate the catabolic state, reaching a better nitrogen balance and liver function tests, without special adverse effects. A special role on liver regeneration is discussed. Antioxidants and supernutrients are special "modern" aspects of nutritional therapy in alcoholic liver disease generally related to the MEOS activation in chronic alcoholism, the excessive production of free radicals, and the depletion of glutathione, membrane phospholipids (specially phosphatidycholine), and vitamin A, E, and C. Natural supplements as soybean polyunsaturated lecithin, with high concentration of phosphatidycholine, or oral supplementation with natural metabolic products depleted from the liver of chronic heavy drinkers, such SAMe, have an interesting rationale based on experimental and clinical findings besides availability and costs. Carotenoids and tocopherols supplementation seems to be an useful tool, but are limited in the case of vitamin A because its special toxicity in chronic alcoholism. Serological markers of metabolism of liver connective tissue are clearly involved in fibrogenesis process and other inflammatory connected events; standardization of laboratory methods surely will result in new possibilities of non-invasive valuation of liver injury, evolution and therapeutic response; special histological damage such as sinusoidal "cappilarization" (type i.v. collagen and laminin), endothelial sinusoidal cell function (seric hyaluronate), or collagenase activity (TIMP-1 or tissue inhibitor of metalloproteinases-1) seems to be valuable by these new technologies.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[New suggestions for the management of alcoholic liver diseases]. 852 63


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