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

Patients with hepatic cirrhosis often are malnourished and wasted. If portal-systemic encephalopathy (PSE) develops, restriction of dietary protein in an attempt to treat encephalopathy may further promote negative nitrogen balance. There is considerable interest in providing nutritional supplements to patients with cirrhosis and PSE which would lead to improvement in nitrogen balance while improving or at least not worsening PSE. Amino acid supplements designed to correct the abnormal amino acid pattern characteristically found in patients with cirrhosis and PSE are under investigation as potential therapeutic agents. The levels of the branched chain amino acids (BCAAs) are decreased in almost all patients with cirrhosis and PSE. The exact mechanism for the reductions in BCAA concentrations is unknown. Furthermore, aromatic amino acids (AAA) and methionine (MET) concentrations are usually increased in these patients. It has been suggested that BCAAs and neutral amino acids compete for transport across the blood-brain barrier and that a decrease in BCAA concentrations promotes entrance of neutral amino acids into the brain. Aromatic amino acids, MET, and their derivatives may have a role in the production of PSE. These observations have increased interest in the potential therapeutic benefit of administering BCAAs to patients with cirrhosis and PSE in order to decrease the entrance of putative toxins into the brain. Treatment trials using BCAAs alone or in solutions containing other amino acids in patients with cirrhosis and PSE have given conflicting results. In one trial, there appeared to be less PSE induced by a BCAA-enriched solution when compared to equinitrogenous dietary protein. However, other controlled studies have not demonstrated any advantage to the addition of BCAAs as compared to placebo with regards to reducing mortality or improving cerebral function in patients with acute cirrhosis and PSE. Some of the differences in study outcomes may relate to the patient population evaluated; the type, amount, and duration of treatment; and whether other therapy was administered. BCAA supplements may also be useful in minimizing or reversing the catabolic state characteristic of patients with cirrhosis. A reduction of increased urinary 3-methylhistidine excretion by infusions of BCAAs in cirrhotic patients suggests an anticatabolic effect. These potential anticatabolic effects of BCAAs are most interesting and deserve further study.
 ...
PMID:Branched chain amino acid therapy in liver disease. 393 6

Patients with stupor or coma from fulminant hepatic failure were found to have high cerebrospinal fluid concentrations of homovanillic acid (HVA) and 5-hydroxyindole acetic acid (5-HIAA), metabolites of dopamine and serotonin respectively. Excessive amounts of their precursors-phenylalanine and tyrosine and free tryptophan-were found in the patients' plasma. Methionine, which participates in dopamine degradation, was also much increased. Similar disturbances were found in patients suffering an acute exacerbation of chronic encephalopathy. These abnormalities would be consistent with other evidence of an increased turnover of serotonin and possibly dopamine in the brain during hepatic encephalopathy.
 ...
PMID:Dopamine and serotonin metabolism in hepatic encephalopathy. 481 89

Serum methionine levels increased to a greater extent in patients with severe liver diseases such as fulminant hepatitis and liver cirrhosis with and without hepatic encephalopathy. However, the concentrations remained unchanged in non-encephalopathic cirrhotic cases associated with hepatocellular carcinoma, and their serum methionine levels increased only moderately even at the time of encephalopathy. At least two different mechanisms of serum methionine elevations, possibly due to release from injured hepatocytes or diminished catabolisms of this amino acid in the damaged liver, could be differentiated; the former would be involved mainly in fulminant hepatitis and the latter in liver cirrhosis. A methionine-loading test performed in cirrhotic patients supported the validity of these considerations. No significant increase of serum methionine levels in cirrhotic patients with hepatocellular carcinoma was observed, possibly by remarkable consumption of this amino acid in hepatoma tissues. During the clinical course of several patients, serial determinations of serum methionine concentrations indicated that the levels varied depending upon alterations in the pathophysiological state of the damaged liver; much higher levels were observed concomitantly with decompensated signs such as ascites, jaundice and hepatic encephalopathy. These results suggest that monitoring of serum methionine levels would be very valuable, especially for judging prognosis and predicting hepatic encephalopathy in severe liver disease.
 ...
PMID:Impaired metabolism of methionine in severe liver diseases. I. Clinical and pathophysiological significance of elevated serum methionine levels. 628

The influence of intravenous infusion of branched-chain amino acids (BCAAs) on brain function in patients with liver cirrhosis and acute hepatic encephalopathy was examined using a double-blind, randomized study design. Five medical centers in France and Sweden participated, and 50 patients were studied. The patients received either BCAAs (40 gm per day) in 5% glucose or 5% glucose alone (placebo) for 5 days or until "wake up". Nutritional support was provided with equal proportions of carbohydrate and fat. During BCAA administration, plasma concentrations of aromatic amino acids and methionine fell (20 to 40%, p less than 0.05 to 0.01), and the ratio of BCAAs to aromatic amino acid concentrations increased significantly. Clinical improvement was seen in 14 of 25 BCAA-treated patients and in 12 of 25 patients receiving placebo (N.S.). EEG responses were similar in the two groups during treatment. In the BCAA group, 10 of 25 patients died in the course of the study, compared to 5 of 25 in the placebo group (N.S.); six patients died from encephalopathy in the BCAA group as compared to three among placebo-treated patients. It is concluded that BCAA administration, in the dose and composition employed in the present study, reduces the concentrations of aromatic amino acids but neither improves cerebral function nor decreases mortality in patients with hepatic encephalopathy.
 ...
PMID:Is intravenous administration of branched chain amino acids effective in the treatment of hepatic encephalopathy? A multicenter study. 634 30

In order to define further the therapeutic role of hemodialytic procedures in acute hepatic failure, 20 pigs with ischemic hepatic necrosis underwent randomized hemodialysis against an electrolyte solution (n = 6), hemofiltration with re-infusion of an electrolyte solution (n = 5), control hemofiltration with re-infusion of autologous ultrafiltrate (n = 4) or no extracorporeal procedure at all (n = 5). Pigs on hemodialytic procedures survived significantly longer (51 +/- 11 hrs) than controls (36 +/- 8 hrs). There were no differences in the duration of survival between hemodialysis and hemofiltration, nor between controls undergoing and those not undergoing an extracorporeal procedure. Electroencephalograms showed more rapid (p less than 0.05) deterioration in control animals than in the treatment group. Putative toxins such as ammonia, glutamine, tyrosine, tryptophan, and methionine all decreased transiently in the treatment group; in the control group a continuous increase in the levels of the putative toxins was observed. Comparison of all pigs surviving 35 hrs or less (n = 6) and animals surviving more than 45 hrs (n = 7) showed that long-term survival was significantly associated with lower plasma ammonia and methionine concentrations and fewer abnormalities on the electroencephalogram 10 hrs after the start of extracorporeal procedures; moreover six of the 7 long-term survivors underwent hemodialysis or hemofiltration procedures. We conclude that hemodialytic procedures prolong survival in pigs with ischemic hepatic necrosis by slowing the development of encephalopathy; this effect of hemodialytic procedures may be mediated by the lowering of plasma ammonia and methionine levels.
 ...
PMID:Large-pore hemodialytic procedures in pigs with ischemic hepatic necrosis; a randomized study. 651 36

Twenty-two patients with cirrhosis and acute encephalopathy who were refractory to medical therapy were entered into a randomized, double-blind prospective trial. This trial consisted of either neomycin or a modified amino acid solution rich in branched chains and low in aromatic amino acids and methionine (F080) in the presence of isocaloric amounts of dextrose. The groups were indistinguishable from each other by clinical or laboratory criteria; they were primarily patients who had undergone operation and they would tolerate only 30 gm of oral protein or intravenous standard amino acids. The group receiving F080 had a faster and more complete improvement in encephalopathy. This improvement correlated with the plasma molar ratio and occurred with a lower mortality rate. In addition, the patients also tolerated twice the amino acid load without encephalopathy and were in positive nitrogen balance. Modified metabolic support is effective in the setting of acute liver failure in chronic cirrhosis, particularly in patients who have undergone operation.
 ...
PMID:Cirrhosis, encephalopathy, and improved results with metabolic support. 662 61

Amino acids and thiobarbituric acid reactive substances (TBARs) in the cerebrospinal fluid (CSF) and plasma were identified and assayed in 5 patients with septic encephalopathy. Levels of all the high molecular weight neutral amino acids (LNAAs) appeared to increase in the CSF. CSF levels of phenylalanine (PHE) and methionine (MET) increased significantly by factors of 20.9 and 9.5, respectively, and the plasma PHE level increased 7.5-fold. No significant changes in branched-chain amino acids were observed in either the CSF or plasma. The CSF/plasma ratios of valine (VAL), tyrosine (TYR), PHE, and MET significantly increased to 0.21, 0.46, 0.52, and 0.52, respectively. TBAR levels increased 4-fold in the CSF and also were slightly increased in the plasma, suggesting that lipid peroxidation in the central nervous tissues is markedly increased. We conclude that increases in LNAA levels and in lipid peroxidation in the central nervous tissues may play important roles in the development of septic encephalopathy.
 ...
PMID:Amino acids and thiobarbituric acid reactive substances in cerebrospinal fluid and plasma of patients with septic encephalopathy. 662 56

A controlled crossover clinical comparison of 40-g/day and 80-g/day vegetable protein diets vs a 40-g/day meat protein diet plus neomycin-milk of magnesia (as control therapy) was performed on 10 cirrhotic patients with mild chronic portal-systemic encephalopathy. The 40-g vegetable protein diet had a high fiber volume and contained low methionine and low aromatic amino acids. The 80-g vegetable protein diet was rich in branched-chain amino acids and fiber, with a similar content of sulfur-containing amino acids as compared to the 40-g meat protein diet. Serial semiquantitative assessments were done, including mental state, asterixis, number connection tests, electroencephalograms and blood ammonia levels. No patient developed deep coma while ingesting either vegetable protein diet or neomycin-milk of magnesia plus 40-g meat protein diet. A significant improvement in the number connection test times was observed during the 40-g vegetable protein diet (P less than 0.05) and during the 80-g vegetable protein diet (P less than 0.05) as compared to their previous 40-g meat protein--neomycin periods. In addition, during the period of 80-g vegetable protein diet, the patients showed a significant improvement in their electroencephalograms (P less than 0.05). The frequency of bowel movements significantly increased (P less than 0.05) during the 80-g vegetable protein diet period. During the 40-g vegetable protein diet, two cirrhotic--diabetic patients experienced hypoglycemia. Three patients complained of the voluminous 80-g vegetable protein diet. Patients with mild portal--systemic encephalopathy may be adequately controlled with vegetable protein diets as a single therapy.
 ...
PMID:Treatment of chronic portal--systemic encephalopathy with vegetable and animal protein diets. A controlled crossover study. 675 33

The amino acid solution, Aminofusin hepar, was evaluated for treatment of hepatic encephalopathy and for parenteral nutrition of patients with liver cirrhosis in correlation to changes in amino acid levels. In contrast to amino acid solutions used for the parenteral nutrition of patients without liver disease, this solution contains an increased proportion of branch chained amino acids and of arginine and ornithine, and a reduced proportion of phenylalanine, methionine, glycine and threonine. The changes in the plasma amino acid levels after infusion of this solution were measured in 4 cirrhotics. The concentration of leucine, isoleucine, valine, ornithine and arginine increased markedly, whereas phenylalanine, methionine, tyrosine, glycine and threonine decreased. The ammonia level in venous blood increased slightly. 4 cirrhotics with encephalopathy were treated for 7 days. In 3 of them the neuropsychiatric symptoms were completely reversed, whereas in the remaining 1 no clinical improvement was achieved in spite of normalization of the plasma aminogramm. In this patient a constant rise of blood ammonia was noted. The indications for special amino acid solutions in liver diseases are discussed.
 ...
PMID:[Parenteral feeding of patients with liver cirrhosis with hepatic encephalopathy]. 677 52

An inherited defect in the glycine cleavage enzyme results in the condition of neonatal glycine encephalopathy which has not responded to the current innovative methods of therapy. A re-examination of the enzyme structure and metabolic pathways, leads us to recommend future clinical evaluation of (1) vitamin-responsiveness, e.g., pyridoxine, folate and lipoic acid, (2) methionine, (3) N5, N10-methylene tetrahydrofolate and (4) alpha-methylserine therapy during the critical period of neonatal brain growth and development.
 ...
PMID:A strategy for glycine encephalopathy therapy. 680 51


<< Previous 1 2 3 4 5 6 7 Next >>