Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sepsis is a major catabolic insult resulting in a peripheral energy deficit which is made up in part by increased breakdown of lean body mass and oxidation of amino acids, principally the branched chain amino acids. The prognosis in any given case of sepsis is difficult to predict, but should theoretically be related to the degree of disturbance in peripheral energy deficit, which may in turn, be related to plasma amino acid pattern. In order to study whether this hypothesis was correct, plasma amino acids and some of their metabolic byproducts, the beta-hydroxyphenylethanolamines, were studied in 25 septic patients, and were used as discriminant variables in a series of computer performed discriminant analyses and multiple regressions. The two functions tested were the degree of metabolic septic encephalopathy as a determinant of the severity of sepsis and the final outcome in the septic patient. Plasma amino acid patterns exhibited elevated levels of the aromatic and sulfur containing amino acids, phenylalanine, tryosine, tryptophan, methionine, cysteine, and taurine, normal concentrations of alanine, and low normal concentrations of the branched chain amino acids, valine, leucine and isoleucine. Arginine levels, as previously noted, were very low. Patients not surviving the septic episode exhibited higher concentrations of aromatic and sulfur containing amino acids, while patients surviving sepsis had higher concentrations of the branched chain amino acids and arginine. When the degree of encephalopathy as a determinant of the severity of sepsis and step wise discriminant analysis with multiple crescent techniques were used, the best discriminant function between patients with and without encephalopathy was found to result from the interaction of cysteine, methionine, phenylalanine, isoleucine, leucine, and valine. These amino acids gave a correct classification in 82% of patients with no encephalopathy, and 80% of patients with septic encephalopathy. When the same amino acids were used for the discriminant analysis for patients dying of sepsis and patients surviving, the best discriminant function was achieved by using plasma concentrations of alanine, cysteine, methionine, isoleucine, arginine, tyrosine and phenylalanine resulting in 91% of the nonsurvivors, and 79% of the survivors correctly classified. The results suggest a close and significant relationship between the deranged energy metabolism and muscle protein breakdown in sepsis, and the outcome. This further suggests a central role for certain amino acids in perhaps predicting the severity of sepsis and its outcome.
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PMID:Plasma amino acids as predictors of the severity and outcome of sepsis. 38 83

Twenty patients with paracetamol(acetaminophen)-induced acute liver damage of varying severity were studied longitudinally with assessment of clinical state, standard liver function tests and radiometric hyaluronate (HYA) assay (Pharmacia). In patients (n = 6) who developed coma, HYA rose rapidly with clinical deterioration to reach a median value of 27,510 micrograms/l, 7 days post-ingestion, which was significantly higher (p less than 0.005) than in patients (n = 7) who exhibited only marked derangement of liver function tests without evidence of encephalopathy, HYA median value of 3240 micrograms/l. These peak values showed no correlation to the peak values of serum alanine aminotransferase (ALT). A third group of patients (n = 7) who were treated with N-acetyl cysteine, did not exhibit any evidence of liver failure and showed no significant rise in levels of HYA or ALT. The data demonstrate that HYA is a rapidly changing marker of liver derangement which appears to follow the clinical course of the patient. The increase to extremely high levels in patients with hepatic encephalopathy, suggests that there is a reversible defect in the hepatic endothelial cell HYA receptor, possibly due to endothelial cell damage or release of toxins from the necrotic liver.
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PMID:Serum hyaluronate as a marker of hepatic derangement in acute liver damage. 191 80

A large Queensland family has an extreme form of Leber hereditary optic neuropathy (LHON) in which several neurological abnormalities and an infantile encephalopathy are present in addition to the characteristic ophthalmological changes. Sequence analysis of the seven mitochondrial genes encoding subunits of respiratory chain complex I (NADH-ubiquinone oxidoreductase) reveals two novel features of the etiology of this mitochondrial genetic disease. The first conclusion from these studies is that the ophthalmological and neurological deficits in this family are produced by a mutation at nucleotide 4160 of the ND1 gene. This nucleotide alteration results in the substitution of proline for the highly conserved leucine residue at position 285 of the ND1 protein. Secondary-structure analysis predicts that the proline replacement disrupts a small alpha helix in a hydrophilic loop. All nine family members analyzed were homoplasmic for this mutation. The second major result from these studies is that the members of one branch of this family carry, at nucleotide 4136 of the same gene, a second mutation, also homoplasmic, which produces a cysteine-for-tyrosine replacement at position 277. The clinical and biochemical phenotypes of the family members indicate that this second nucleotide substitution may function as an intragenic suppressor mutation which ameliorates the neurological abnormalities and complex I deficiency.
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PMID:Leber hereditary optic neuropathy: involvement of the mitochondrial ND1 gene and evidence for an intragenic suppressor mutation. 173 27

Taurine is an important age- and compartment-specific part of the pool of free amino acids in all human tissues and fluids examined. Besides an active taurine transport system, the mechanisms to assure compartment-specific taurine-homeostasis in humans is presumably due to a compartment-specific taurine synthesis. By the identity of cysteine-sulfinic acid - and glutamate-oxalate transaminase as well as of cysteine-sulfinic acid - and glutamic acid decarboxylase taurine biosynthesis via cysteine-sulfinic acid shows direct metabolic relationship between biochemical pathway of cysteine-sulfinic acid and taurine on one side, and of the dicarbonic acid and their biological decarboxylates on the other side. In the parenteral and enteral nutrition of premature babies as well as of adults with portosystemic encephalopathy or with extreme thiamine deficiency, there is - besides an inconstant parallel of exogenous taurine supply and plasma taurine homeostasis - a constant parallel between definitely lowered plasma taurine concentrations and comparably distinct disturbance of the homeostasis of the dicarbonic acids and/or their biosynthetic products. A metabolic connection seems likely. The hypothesis of Sturman et al. in 1976 that taurine is an essential part of the human nutrition at least in the premature or full-term newborn phase of life could not be supported in the subsequent studies of different groups of authors - neither in relation to the nitrogen balance, childhood-development, hepatic cellular function, biliary-acid metabolism, intestinal fat absorption nor any organ-specific function. The nutritional value of taurine in humans still remains unclear in regard to specific physiologic as well as specific pathophysiologic phase of metabolism.
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PMID:[Taurine--recent views and importance for artificial feeding]. 313 85

Development of metabolic acidosis (pH < 7.30) or the combination of encephalopathy grade III-IV, coagulopathy (PT > 100s) and oliguric renal failure are associated with a poor prognosis in paracetamol-induced fulminant liver failure. It is important to administer N-acetylcysteine as soon as possible after the overdose, but N-acetyl-cysteine also seems to improve survival when given 36-80h following ingestion. Liver transplantation has been performed in some patients with paracetamol-induced fulminant liver failure, but convincing evidence that transplantation improves survival in this group of patients is still lacking. We discuss the difficulties met in deciding if and when to perform liver transplantation. Renal failure may develop some days after paracetamol poisoning, even in the absence of severe liver damage, and haemofiltration and haemodialysis may be necessary.
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PMID:[Treatment of paracetamol poisoning. An indication for liver transplantation?]. 820 19

The HIV1-PAR strain, isolated from the cerebrospinal fluid of an HIV1-seropositive man suffering from encephalopathy, replicated well in cord blood lymphocytes, poorly in peripheral blood mononuclear cells, and to different levels in blood-derived macrophage (BDM) cultures prepared from different blood donors. In marked contrast to its replication in primocultures, it did not grow in CEM and U937 cell lines. HIV1-PAR production in BDM was inhibited by more than 90% after treatment with OKT4A or 13B8.2 monoclonal antibodies (mAb) binding to adjacent epitopes of the D1 domain of the CD4 molecules. A lower but significant inhibitory effect was observed after BDM treatment with BL4 and OKT4 mAb, directed to the D2 and D3 domain of the CD4 molecule, respectively. The entire HIV1-PAR envelope glycoprotein gene was amplified by polymerase chain reaction and sequenced. The deduced amino acid sequence of HIV1-PAR gp160 revealed the presence of 847 amino acids and 86% homology with the HIV1 LAV virus prototype. An alignment of the amino acid sequence of the envelope glycoprotein of HIV1-PAR and HIV1-LAV showed that the differences were mostly clustered within the five variable regions. Five CD4-binding domains, the gp120/gp41 cleavage site, the putative gp41 fusion domain and 21 out of the 22 cysteine residues were conserved in both isolates. The results further confirm the macrophage-tropic character of the HIV1-PAR virus.
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PMID:Characterization of HIV1-PAR, a macrophage-tropic strain: cell tropism, virus/cell entry and nucleotide sequence of the envelope glycoprotein. 844 73

We report three infants with the diagnosis of molybdenum cofactor deficiency. The key findings leading to diagnosis were neonatal seizures unresponsive to treatment, craniofacial dysmorphic features, hyperexcitability, low blood uric acid levels, and neuroimaging findings. The parents were consanguineous in two of these patients. The diagnosis was established by the presence of low blood uric acid levels, positive urine sulfite reaction, quantitative aminoacid analysis, and high-voltage electrophoresis of the urine sample showing a typical increase of S-sulfo-L-cysteine. Skin fibroblast cultures confirmed the diagnosis. Magnetic resonance imaging findings were suggestive of encephalomalacia with cystic changes due to hypoxic-ischemic encephalopathy. We conclude that molybdenum cofactor deficiency must be included in the differential diagnosis of patients presenting with intractable seizures in the newborn period who have computed tomography and magnetic resonance imaging findings reminiscent of those of hypoxic-ischemic encephalopathy, and the urine sulfite dipstick test can be a part of the evaluation of these infants in neonatal intensive care units.
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PMID:Molybdenum cofactor deficiency: report of three cases presenting as hypoxic-ischemic encephalopathy. 1133 61

Chloroacetaldehyde, a metabolite of the anticancer drug ifosfamide, may be responsible for serious adverse effects like encephalopathy in ifosfamide chemotherapy. In this study, we demonstrate that chloroacetaldehyde, but not ifosfamide, induces cell death in human osteosarcoma Saos-2 cells and we investigated the mechanism by which this occurs. Chloroacetaldehyde above 30 micromol/l induced significant cell death in a time-dependent manner. Thiol compounds such as N-acetyl cysteine, glutathione and dithiothreitol protected the cells against chloroacetaldehyde-induced cell death, although other nonthiol compounds and the antioxidative enzymes superoxide dismutase and catalase did not, suggesting that reactive oxygen species might not mediate cell death. In cells exposed to chloroacetaldehyde, levels of both total thiols and glutathione were significantly reduced. Chloroacetaldehyde also collapsed the mitochondrial membrane potential of these cells, induced the release of cytochrome c from mitochondria to the cytosol and significantly reduced cellular ATP levels during the course of death. The mitochondrial potential collapse was also prevented by thiol compounds. Flow cytometric analyses by means of annexin-V and propidium iodide double staining and immunofluorescence staining of active caspase-3 revealed that cells subjected to a lethal dose of chloroacetaldehyde displayed features characteristic of necrosis and that caspase-3 was not activated in response to chloroacetaldehyde. Taken together, these findings suggest that Saos-2 cells exposed to chloroacetaldehyde die by necrosis resulting from a decrease in intracellular thiols, disruption of the mitochondrial membrane potential and the depletion of cellular ATP.
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PMID:Necrotic pathway in human osteosarcoma Saos-2 cell death induced by chloroacetaldehyde. 1741 23

Human health in the past and presently is influenced by the amounts and proportion of chemical elements to which humans have been exposed. Arsenic, as a therapeutic agent was known to ancient Greeks and Romans. Ehrlick introduced organic arsenicals as anti linetic agents but with advent of penicillin these have nearly become obsolete. Once considered toxic, harmful to humans, arsenic is now considered an essential ultra trace element at least in animals. Now the impact of arsenic on health is more from industrial and environmental than medicinal exposure. This article reviews human exposure to arsenic in non occupational population, mostly through drinking water which is a worldwide problem, more so in south East Asia. Sources of arsenic, normal and abnormal levels in blood and tissues levels, old and new methods of estimation of arsenic, mechanism of action of arsenic in experimental animal is briefly reviewed. Old described clinical manifestation of arsenic in humans is briefly reviewed and newly described clinical manifestations in human with special emphasis on atherosclerosis, liver and diabetes are discussed. Proposed biological mechanisms in experimental animals included up regulation of inflammatory signals like cytokines and TNF-alpha, oxidative stress, hypomethylation, decreased DNA repair and apoptosis, cell proliferation, angiogenesis, activation of several enzymes like methyl transferase which converts inorganic arsenic to MMA and DMA, and GSH in in-vivo and in-vitro in experimental rat liver slices. Experimentally NAC (N-Acetyl Cysteine) treatment attenuates oxidative stress in atherosclerosis apoptosis and liver injury. GSH probably plays an important role in deactivation of the intermediate products of arsenic metabolism and prevents peroxidation of membrane lipids. Chronic human exposure has been linked to several systems in the human body: dermal (exfoliative dermatitis, keratosis, vitiligo, skin cancer), peripheral neuropathy, encephalopathy, bronchitis, pulmonary fibrosis, hepatosplenomegaly resembling NCPF, portal hypertension, peripheral vascular disease and BFD, arteriosclerosis and cancers of lung, urinary bladder, other internal organs and diabetes. Experimental and epidemiological evidence support diabetes effect of high level arsenic exposure. Low and moderate exposure to arsenic in drinking water is widely prevalent and may play a role in diabetes prevalence and needs to be studied further. Role of arsenic in Indian arteriosclerosis, diabetes and liver diseases, (cirrhosis, NCPF), need to be studied further. Study of mechanisms and enzymes mentioned need to be studied in humans exposed to arsenic and other xenobiotics. Measuring arsenic exposure, metabolic and biologic effects by newly described and simpler urine proteomics may accelerate our understanding of arsenic on health consequences.
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PMID:Arsenicosis: review of recent advances. 2175 19

A compromised intrauterine environment that delivers low levels of oxygen and/or nutrients, or is infected or inflammatory, can result in fetal brain injury, abnormal brain development and in cases of chronic compromise, intrauterine growth restriction. Preterm birth can also be associated with injury to the developing brain and affect the normal trajectory of brain growth. This review will focus on the effects that episodes of perinatal hypoxia (acute, chronic, associated with inflammation or as an antecedent of preterm birth) can have on the developing brain. In animal models of these conditions we have found that relatively brief (acute) periods of fetal hypoxemia can have significant effects on the fetal brain, for example death of susceptible neuronal populations (cerebellum, hippocampus, cortex) and cerebral white matter damage. Chronic placental insufficiency which includes fetal hypoxemia, nutrient restriction and altered endocrine status can result in fetal growth restriction and long-term deficits in neural connectivity in addition to altered postnatal function, for example in the auditory and visual systems. Maternal/fetal inflammation can result in fetal brain damage, particularly but not exclusively in the white matter; injury is more pronounced when associated with fetal hypoxemia. In the baboon, in which the normal trajectory of growth is affected by preterm birth, there is a direct correlation between a higher flux in oxygen saturation and a greater extent of neuropathological damage. Currently, the only established therapy for neonatal encephalopathy in full term neonates is moderate hypothermia although this only offers some protection to moderately but not severely affected brains. There is no accepted therapy for injured preterm brains. Consequently the search for more efficacious treatments continues; we discuss neuroprotective agents (erythropoietin, N-acetyl cysteine, melatonin, creatine, neurosteroids) which we have trialed in appropriate animal models. The possibility of combining hypothermia with such agents or growth factors is now being considered. A deeper understanding of causal pathways in brain injury is essential for the development of efficacious strategies for neuroprotection.
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PMID:The biological basis of injury and neuroprotection in the fetal and neonatal brain. 2152 38


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