Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ammonia clearance, portal blood ammonia, and amino acid concentrations were studied during induction of cirrhosis by carbon tetrachloride in rats. Exposure to CCl4 vapors twice weekly for 7-16 weeks doubled orotic acid excretion. If exposure was discontinued for 7 days, the orotic acid excretion decreased despite the presence of cirrhosis proven histologically. Replacement of dietary casein with soybean protein eliminated the CCl4-induced orotic aciduria in growing rats but not in adults. Supplementation of casein with 1.5% arginine did not prevent CCl4-induced orotic aciduria. [14C]Orotate uptake into RNA and DNA of liver was not impaired. Perfusion of livers of cirrhotic animals with ammonia concentrations between 0.2 and 3.0 mM revealed no significant decreases in urea synthesis rates due to cirrhosis and no increase in the tendency to make orotic acid at a given ammonia concentration. However, ammonia uptake by cirrhotic livers was significantly reduced, resulting in higher ammonia concentrations in the effluent when there was moderate-to-severe cirrhosis. Portal blood samples taken from rats exposed to CCl4 had higher ammonia concentrations as cirrhosis worsened. The results lend support to the "intact hepatocyte" hypothesis of cirrhosis which attributes metabolic abnormalities to intrahepatic shunts.
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PMID:Orotic acid overproduction in experimental cirrhosis of rats. 272 54

Cerebral blood flow (CBF), measured by the non-invasive 133-Xenon inhalation method, plasma levels of ammonia (NH3) and free tryptophan (fTRP) were determined in 30 cirrhotic patients without overt encephalopathy. Psychometric evaluation detected subclinical hepatic encephalopathy (SHE) in 20 of them, and was normal in the other 10. A significant CBF difference (p less than 0.05) was found between the SHE and the non-SHE patients. fTRP levels were significantly (p less than 0.05) higher in patients with SHE than in those without SHE, and a significant negative correlation (p = 0.003) was found between CBF values and fTRP in the whole group of patients. NH3 did not differ in the two subgroups and did not correlate with CBF values. It is concluded that CBF could have some implications in SHE, although its relevance is still unclear. The negative correlation between CBF and fTRP prompts further investigation concerning the relationships between plasma fTRP, brain serotonin, cerebral metabolism and blood flow in the development of brain derangement during cirrhosis.
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PMID:Cerebral blood flow and plasma free tryptophan in cirrhotics with and without hepatic encephalopathy. 279 14

The aim of this study was to evaluate the contribution of gluconeogenesis from amino acids in the development of fasting and absorptive hyperammonemia in cirrhosis. Somatostatin (SRIF), which is known to inhibit the hepatic disposal of gluconeogenic amino acids, was administered in a continuous infusion (500 micrograms/h) for 90 min before and 5 h after a protein meal (240 g of meat) in 11 overnight fasting patients. Plasma glucagon, insulin, gluconeogenic amino acids (GAA: alanine, serine, glycine, and threonine) and ammonia (NH3) were evaluated before the infusion, immediately before, and at 1, 3, and 5 h after the meal. As control study, the same protocol was randomly repeated in a different day with saline infusion. During the latter, a direct correlation was found between fasting glucagon and ammonia (r = 0.68; p less than 0.05). Fasting glucagon, insulin, and NH3 did not change, whereas alanine (p less than 0.05) and the GAA sum decreased (p less than 0.01). When SRIF was infused, fasting glucagon (p less than 0.05), insulin (p less than 0.05), and NH3 (p less than 0.05) decreased. Alanine did not change, and GAA sum increased (p less than 0.02). No correlations were found by plotting changes in glucagon or GAA sum and NH3. After the meal, SRIF infusion abolished the plasma response of glucagon and markedly reduced that of insulin, so that their area under the curve (AUC0-5) were reduced (p less than 0.005, for both), with respect to control study. Moreover, the AUC0-5 of alanine (p less than 0.005) and GAA sum (p less than 0.005) were increased, suggesting a reduced disposal of these compounds. In spite of this, the meal-induced early increase and the AUC0-5 of plasma NH3 observed during SRIF and saline infusion did not differ. Our results do not confirm the importance of gluconeogenesis from alpha-amino-nitrogens in determining the fasting ammonemia of cirrhosis, and suggest that this metabolic pathway does not significantly influence the protein meal-induced exacerbation of plasma ammonia.
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PMID:Role of gluconeogenesis from amino acids in determining fasting and absorptive levels of plasma ammonia in cirrhosis. 289 85

The activity of the lysosomal enzyme, beta-hexosaminidase, is increased in plasma of patients with various forms of liver disease as well as in plasma from rats with experimental cholestasis or cirrhosis. In this experimental study in the rat, the effect of porta-caval shunt, ammonia infusion and ethanol feeding on plasma beta-hexosaminidase activity was studied. Porta-caval shunted animals had significantly increased plasma beta-hexosaminidase activity compared to sham-operated animals. Ammonia infusion in porta-caval shunted rats resulted in a further increase of plasma enzyme activity. Ethanol feeding for different periods of time (1 day to 4 weeks) did not have any influence on plasma beta-hexosaminidase activity.
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PMID:The effect of porta-caval shunt, ammonia infusion and alcohol administration on rat plasma beta-hexosaminidase. 296 73

Ammonia and glutamine metabolism was studied in slices from normal, fatty and cirrhotic human livers. The liver disease was evaluated by histological examination. With respect to ammonia removal, urea and glutamine synthesis in human liver represent low and high affinity systems with k0.5(NH4+) values of 3.6 and 0.11 mM, respectively. Compared with normal control livers, cirrhotic livers showed a decreased glutamine synthesis from NH4Cl by about 80%. The same was true for urea synthesis. Conversely, flux through hepatic glutaminase was increased in cirrhosis 4-6-fold. These changes in hepatic glutamine and ammonia metabolism were observed regardless of whether reference was made to liver wet weight, DNA or protein content. Acetazolamide inhibited urea synthesis in cirrhotic liver slices by about 50%, indicating that mitochondrial carbonic anhydrase is required for urea synthesis also in cirrhosis. There was a significant correlation between the in-vitro determined capacity for urea synthesis from NH4Cl and the in-vivo determined plasma bicarbonate concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ammonia and glutamine metabolism in human liver slices: new aspects on the pathogenesis of hyperammonaemia in chronic liver disease. 314 7

Elevated plasma ammonia level in hepatic cirrhosis has been attributed to a lack of conversion of enteric ammonia into urea or to its entry into systemic circulation via portasystemic shunting, or to both. It is exaggerated by excessive protein intake. Because hyperglucagonemia is well documented in cirrhosis and a protein meal is an effective glucagon secretagogue, plasma glucose, insulin, glucagon, and ammonia levels were determined in 50 cirrhotic patients after an overnight fast. Effects of a protein meal were also assessed in 20 of these patients. Plasma glucose was normal and remained unaltered after a protein meal. Insulin, glucagon, and ammonia levels were elevated, but only in patients with advanced liver dysfunction. Ammonia levels correlated significantly with glucagon (r = 0.61, p less than 0.001), but not with insulin or glucose levels. Insulin and glucagon levels rose after a protein meal in all patients and controls; whereas a significant rise in the ammonia level occurred only in decompensated cirrhotics. Elevation of the ammonia level was significantly correlated with fasting glucagon (r = 0.54, p less than 0.05), as well as with glucagon response (r = 0.65, p less than 0.01), but not with basal insulin or insulin response. Furthermore, the rise in ammonia level occurred too early to be accounted for by enteric generation. Finally, direct effects of glucagon administration on plasma glucose and serum ammonia were examined in 15 cirrhotic patients. Glucose response was significantly blunted in cirrhotic patients as compared with normal subjects, whereas serum ammonia rose promptly but only in cirrhotics, with maximum rise being noted in cirrhotic patients with advanced liver dysfunction. This study, therefore, suggests that hyperglucagonemia may contribute significantly to hyperammonemia in hepatic cirrhosis.
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PMID:Elevated plasma ammonia level in hepatic cirrhosis: role of glucagon. 388 8

The effects of branched-chain amino acid (BCAA)-enriched nutrient mixture (nutrient-mixture) on the nitrogen metabolism and nutritional state were clinically investigated in 10 patients with liver cirrhosis. Nutrient-mixture-supplemented diet was prepared by adding 150 g nutrient-mixture daily to low-protein diet, and comparisons were made with a regular diet (control diet). Each diet supplied 2,100 kcal energy and 80 g protein per day. Patients were given control diet for 2 weeks and thereafter treated successively with nutrient-mixture-supplemented and control diet each for 2 weeks. Nitrogen balance improvement and positive balance were observed during the feeding of nutrient-mixture-supplemented diet. The composition of nitrogen compounds in urine and the fecal nitrogen excretion did not alter during the test period. Plasma aromatic amino acid (AAA) concentrations decreased and BCAA/AAA molar ratios increased significantly during the 1st and 2nd week of nutrient-mixture-supplemented diet administration. Plasma methionine concentration also decreased in the 1st week. Plasma pre-albumin levels rose significantly during the 1st and 2nd week of nutrient-mixture-supplemented diet administration, and the number connection test improved significantly following the supplemented diet. These results suggest that the use of nutrient-mixture in the nutritional treatment of liver cirrhosis had no deleterious effects on nitrogen metabolism and is useful for the improvement of plasma amino acid imbalance and protein-energy malnutrition.
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PMID:Nutritional treatment of liver cirrhosis by branched-chain amino acid-enriched nutrient mixture. 406 64

The Number Connection Test (NCT) by Harold O. Conn was tested for its usefulness for diagnosis and treatment control of portasystemic encephalopathy in out-patients. For this purpose in 30 patients with liver cirrhosis the time in the NCT was determined and the serum ammonia level (NH3) was measured before the treatment with lactulose and neomycin was started. Moreover, 12 clinical symptoms and 10 laboratory parameters were tested for correlation with the NCT-time. We found a positive correlation between the NCT-time and NH3 serum level. For the prediction of the NCT-time the multiple linear regression yielded the combination of NH3 with the proof of ascites and palmar erythema as the best subset of predictor variables. By means of the NCT the effectiveness of the treatment with lactulose and neomycin was demonstrated. We recommend the NCT for the clinical routine in particular for the early diagnosis and for treatment control of portasystemic encephalopathy in patients with liver cirrhosis.
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PMID:[Ambulatory diagnosis and therapy control of portasystemic encephalopathy in patients with liver cirrhosis]. 409 54

Hospitalized patients with hepatic insufficiency often suffer from severe catabolic states and are in urgent need of nutritional support during their acute illness. Protein intolerence, however, remains a significant problem with respect to the provision of adequate nutrition, either enterally or parenterally. The following report is an anecdotal series of 63 consecutive patients in a large urban hospital treated prospectively with nutritional support using a prototype high branched-chain amino acid solution (FO80) given by technique of total parenteral nutrition by the subclavian or internal jugular route with hypertonic dextrose. Sixty-three patients, of which 42 had chronic liver disease (cirrhosis) with acute decompensation and 17 with acute hepatic injury as well as four with hepatorenal syndrome, are the subject of this report. All required intravenous nutritional support and were either intolerant to commercially available parenteral nutrition solutions or were in hepatic encephalopathy at the time they were initially seen. The cirrhotic patients had been hospitalized for a mean of 14.5 +/- 1.9 days before therapy, had a mean bilirubin of 13 mg/100 ml, and had been in coma for 4.8 +/- 0.7 days despite standard therapy. Patients with acute hepatitis had been in the hospital for 16.2 +/- 4.1 days before therapy, had a mean bilirubin of 25 mg/100 ml, and had been in coma 5.2 +/- 1.6 days before therapy. Routine tests of liver function, blood chemistries, amino acids, EEGs, and complex neurological testing including Reitan trailmaking tests were used in the evaluation of these patients. Up to 120 grams of synthetic amino acid solution with hypertonic dextrose was tolerated in these patients with improvement noted in encephalopathy of at least one grade in 87% of the patients with cirrhosis and 75% of the patients with hepatitis. Nitrogen balance was achieved when 75 to 80 grams of synthetic amino acids were administered. Survival was 45% in the cirrhotic group and 47% in the acute hepatitis group. Encephalopathy appeared to correlate with individual amino acids differentially in the various groups and with the ratio between the aromatic and the branched-chain amino acids. Ammonia did not correlate with either the degree of encephalopathy or improvement therefrom. In 24 Patients therapy for hepatic encephalopathy was limited to infusion of the branched-chain enriched amino acid solution only, with wake-up in 66% of this group. The results strongly suggest that in protein intolerant patients requiring nutritional support, infusion with branchedchain enriched amino acid solutions is well tolerated with either no worsening of or improvement in hepatic encephalopathy coincident with the achievement of nitrogen equilibrium and adequate nutritional support.
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PMID:Infusion of branched-chain enriched amino acid solution in patients with hepatic encephalopathy. 628 73

The altered plasma amino acid pattern (i.e. increased levels of aromatic amino acids and decreased levels of branched chain amino acids) is a characteristic feature of cirrhotic patients. Recently it has been proved that an increased net degradation of BCAA is positively correlated to the plasma NH3 level, strongly suggesting that these amino acids are molecularly involved in glutamine synthesis to detoxify ammonia in skeletal muscle. Lactulose, a synthetic, nonabsorbable disaccharide, is believed to actively promote excretion of ammonia from the body by causing it to be trapped in the acidified fecal stream and making it unavailable for absorption. Therefore therapy with lactulose could determine an increase of BCAA. The present study was undertaken to examine plasma amino acid pattern of ten patients with liver cirrhosis before and after lactulose therapy. No statistically significant changes of amino acids were observed.
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PMID:[Plasma amino acids in patients with liver cirrhosis treated with lactulose]. 652 9


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