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)

Free amino acid (AA) concentrations in plasma and quadriceps femoris muscle were determined in 19 healthy volunteers and in 16 patients with hepatic cirrhosis and portal hypertension. Nutritional state was impaired as judged by overt muscle wasting (9/16), triceps skinfold thickness less than 70% of normal in 8/14 (57%), and creatinine-height index below 70% in 5/12 (42%). In the plasma of patients the typical amino acid pattern of cirrhosis was to be observed: Elevation of tyrosine and methionine (p less than 0.01), uniform reduction of branched chain amino acids (p less than 0.001) resulting in a decreased molar ratio of BCAA/AAA from 2.85 +/- 0.05 in normal individuals to 1.35 +/- 0.12 in cirrhotics (p less than 0.001). Levels of the gluconeogenic AA glutamine, glutamate, aspartate, alanine, glycine, threonine, serine and lysine were lowered (p less than 0.05). In muscle of cirrhotics, intracellular AA concentrations exhibited a similar pattern with two major exceptions: Tyrosine and phenylalanine were augmented (p less than 0.001). Surprisingly, BCAA levels were altered heterogeneously; those of gluconeogenic BCAA decreased: Valine from 0.34 +/- 0.03 to 0.20 +/- 0.03 mmol/l (p less than 0.001), isoleucine 0.09 +/- 0.01 to 0.05 +/- 0.02 mmol/l. However, the concentration of ketogenic leucine remained unaltered in muscle. Nevertheless, the molar ratio of BCAA/AAA was considerably reduced from 3.70 +/- 0.04 to 0.81 +/- 0.08 (p less than 0.001). Most of the gluconeogenic AA exhibited reduced intramuscular concentrations, but glutamine levels were normal. The pattern of plasma and muscle free AA in hepatic cirrhosis is thus characterized by accumulation of aromatic AA and by depletion of gluconeogenic AA, especially BCAA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characteristic pattern of free amino acids in plasma and skeletal muscle in stable hepatic cirrhosis. 231 39

The goal of this study was to evaluate the presence of extrahepatic damage and the uniformity and reversibility of the histological findings in CCl4-induced liver cirrhosis in the rat. To verify these findings rats were sacrificed 2 and 10 weeks after a treatment consisting of ten intragastric doses of CCl4, administered weekly. All treated rats developed an irreversible micronodular cirrhosis with no damage to the brain, kidney and pancreas. Moreover, rats sacrificed 2 weeks after the last CCl4 dose showed a number of functional alterations usually observed in man. In particular, low branched chain/aromatic amino acids (BCAA/AAA) plasma ratio, high ammonia, low zinc and high insulin with normal blood glucose were obtained.
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PMID:Carbon tetrachloride-induced experimental cirrhosis in the rat: a reappraisal of the model. 262 82

To clarify the clinical significance of specific plasma amino acid abnormalities occurring in liver disorders with portal-systemic shunting, plasma amino acids and insulin levels were measured in idiopathic portal hypertension (IPH), extrahepatic portal occulusion (EHPO), and liver cirrhosis (LC). Three branched chain amino acids (BCAA: valine + leucine + isoleucine) were decreased in all three diseases in comparison with controls. Since plasma insulin measured during oral glucose tolerance tests did not specifically rise in LC, reduction of BCAA is not merely ascribed to hyperinsulinemia. Either portal-systemic shunting or some extent of liver damage may contribute to a fall in BCAA. Two aromatic amino acids (AAA: phenylalanine + tyrosine), which were within the normal range in EHPO and IPH, showed a marked increase in LC. Thus, changes of AAA probably mainly reflect the severity of the liver disease. The molar ratio of BCAA/AAA (MR) significantly correlated with ICG k, ICG R15, PT and the sum of blood ammonia in an oral ammonia tolerance test which may reflect the degree of hepatic disorder. MR diminished in the following decreasing order: controls, EHPO, IPH and LC.
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PMID:Plasma amino acid abnormalities in liver disease: comparative analysis of idiopathic portal hypertension, extrahepatic portal occlusion and liver cirrhosis. 277 20

Ninety-five patients with liver cancer and cirrhosis who had undergone hepatic lobectomy or partial hepatectomy were studied. According to nutritional protocol based on experimental results, a large quantity of fresh frozen plasma (FFP), and BCAA-enriched amino acids at 30 kcal/kg/d as an energy source were administered postoperatively for 7-10 days with strict restriction of sodium and total fluid volume. An elemental diet for liver dysfunction (ED-H) was given to 13 patients at more than 1,500 kcal/d via a naso-duodenal feeding tube for 7-14 days. Six patients were given 15 g/d of BCAA granules after discharge for as long as possible. Serum levels of TP, Alb, T.Bil and PT were kept moderately high in the IVH and ED-H group. Although BCAA/AAA molar ratio was kept high when IVH or ED-H was provided, it gradually fell if nutritional management was discontinued. This ratio was maintained within normal limits by oral administration of BCAA granules. According to the Child classification, 1,2,3 and 5-year cumulative survival rates were 80.9, 62.9, 44.1 and 25.5% for Child A, 70.0, 43.1, 43.1 and 0% for Child B, and 50.0, 25.0, 0 and 0% for Child C, respectively. These data indicate the importance of nutritional support for improvement of nutritional status and for obtaining a better prognosis. Oral BCAA supplementation should be useful for the performance of long-term nutritional management for cancer patients with liver cirrhosis.
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PMID:[Evaluation of the nutritional management of patients with liver cancer and cirrhosis]. 338 29

Toxic protein metabolites are assumed to play an important role in the multifactorial pathogenesis of hepatic encephalopathy (HE). To investigate this, we examined the serum levels of free amino acids, free phenols and indoles in 100 healthy adults, and in 124 liver cirrhotics with HE and 80 without HE. We found a significant increase in free serum phenols and indican already in liver cirrhosis without portal hypertension (PH) and HE. In stage III and IV HE large amounts of p-hydroxy-phenyl lactic acid were detected, which was not the case in cirrhotics without HE. In HE the increase in free serum phenols and indican was much higher than that of the mother substances tyrosine and tryptophan. The quotient BCAA/AAA was decreased significantly already in PH without HE. In addition to the increased formation by intestinal bacteria, a diminished oxidative capacity of the cirrhotic liver seems to be one of the main causes of the increased serum levels of toxic protein metabolites in HE.
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PMID:The role of protein metabolism in 204 liver cirrhotics with and without hepatic encephalopathy. II. Amino acids, free phenols and indoles. 372 89

Changes in amino acid concentrations in plasma during a 100 g oral glucose tolerance test were investigated in patients with liver cirrhosis and in healthy controls. In the controls, almost all amino acid concentrations reached a nadir about 3 hours after glucose loading, then returned to initial levels after 6 hours. Immunoreactive insulin levels reached a peak about 30 minutes after loading, then decreased gradually, reaching initial levels after 6 hours. In the controls, the decrease ratios, defined as maximum decrease during the 3 hours after loading/initial concentration in plasma, were 0.607 and 0.554 for isoleucine (Ile) and leucine (Leu) respectively and 0.382 for valine (Val) which is significantly lower than for Ile or Leu. A similar tendency was recognized in patients with liver cirrhosis. The initial concentration of tyrosine (Tyr) and phenylalanine (Phe) in liver cirrhosis was significantly higher and their decrease ratios were significantly lower than in controls. Though no difference was observed between initial concentrations of tryptophan (Trp) in controls and liver cirrhosis patients, the decrease ratio of Trp in liver cirrhosis was lower (0.061) than that of controls (0.279) (p less than 0.001). The value, t-Trp/BCAA + AAA, i.e. total Trp concentration (mmol/l)/concentration (mmol/l) of branched chain amino acids (BCAA, Ile + Leu + Val) plus aromatic amino acids (AAA, Tyr + Phe), which is known to correlate with the brain Trp concentration of rats (Fernstrom, J. D. & Wurtman, R. J. (1972) Science 178, 414-416), changed significantly from 9.6 +/- 2.4 (mean +/- 1 SD) at the initiation to 12.9 +/- 3.3 at 3 hours after loading in controls (p less than 0.001), and in liver cirrhosis it changed from 10.3 +/- 1.9 to 15.8 +/- 3.1 (p less than 0.001).
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PMID:Changes in plasma amino acids during the oral glucose tolerance test and the effect of these changes on hepatic encephalopathy. 389 65

Acute hepatic encephalopathy in 70 cirrhotic patients was monitored during parenteral administration of amino acids between January 1979 and January 1984. The diagnosis of cirrhosis was confirmed by needle biopsy, and HE by conventional clinical and EEG parameters. The infusion of AA solutions was initiated 48 h after admission and during a 5-day period: 34 patients received a control aminoacid solution, a commercially available AA mixture (Azonutril), and 36 patients a modified solution enriched in BAA prepared from crystallized AA dissolved in distilled water. The calorie intake for both groups was 1600 calories per day from glucose and lipid emulsion. No significant difference was noted based on clinical evolution, even though the plasma AAA/BAA ratio was corrected using the modified AA solution. Of the 34 patients in Group 1: 10 improved, 14 were unchanged, 10 deteriorated and 7 died. Of the 36 patients in Group 2: 12 improved, 14 were unchanged, 10 deteriorated and 7 died. EEG tracing evolved in parallel fashion. The authors conclude that modified AA solutions are ineffective in the treatment of acute hepatic encephalopathy in cirrhotic patients.
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PMID:Treatment of acute hepatic encephalopathy in cirrhotics with a branched-chain amino acids enriched versus a conventional amino acids mixture. A controlled study of 70 patients. 407 69

The aims of this study were: 1. the assessment of the nitrogen balance (NB) in both compensated and encephalopathic cirrhotics, 2. the evaluation of the efficacy of a new therapeutic approach: amino acid solutions enriched with branched chain (BCAA) but poor in aromatic (AAA) amino acids. Solutions containing only BCAA were also employed: 42 cirrhotics were divided into the following groups: 1st group (26 cases), cirrhosis without hepatic encephalopathy (HE); 2nd group (16 cases), cirrhosis with HE. Six patients (23%) in the 1st group showed a positive NB at the beginning; 20 (77%) were negative; 18 of them were fed an oral diet (0.8 g protein/kg/day; 35 cal/kg/day) as a result of which they were brought into a positive NB within 5 days (from - 7.38 +/- 0.95 to + 3.67 +/- 0.46 g N/24 h). In two cases the diet failed to give a positive NB, so it was replaced by a BCAA enriched solution infusion (NB raised from - 1.0 +/- 5.4 g N/24 h). Patients in the 2nd group were put on total parenteral nutrition (TPN); two cases receiving glucose alone achieved a positive NB only when BCAA enriched solutions were added (from - 4.0 to + 3.0 g N/24 h). Four patients treated for 3 days with BCAA alone did not achieve a positive NB; in these cases likewise, BCAA enriched solutions were added in order to achieve a positive NB (from - 0.8 to + 4.2 g N/24 h); all 14 cases treated from the beginning with glucose + BCAA enriched solutions became positive, on average, within 5 days (from - 4.82 +/- 0.89 to + 3.15 +/- 0.61 g N/24 h). In addition to the NB, other parameters (blood ammonia, BCAA/AAA ratio, blood urea, electroencephalograms) and clinical symptoms were beneficially influenced by these solutions.
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PMID:Negative nitrogen balance in cirrhotics. (A correct therapeutic approach). 729 72

The portacaval anastomosis (PCA) rat model and human cirrhosis have many metabolic and nutritional abnormalities in common, such as growth retardation, hepatic and gonadal atrophy, and hyperammonemia. The severity of these abnormalities is variable and may be related to a number of factors, including portal pressure, portosystemic shunting, dietary intake, and how efficiently food is used. Therefore, this rat model was used to study these variables with the intent of gaining insights for improving the management of portal hypertension and malnutrition in human cirrhosis. A nonsuture end-to-side PCA (N = 100) or sham surgery (N = 71) was performed in 100 male rats. Four weeks after surgery, body and organ weights, food intake, serum ammonia, and serum amino acids were measured at death. In a subgroup of rats, (sham 7; PCA 34) portal venous pressure, degree of portosystemic shunting, and organ and body weights were obtained at death. Growth, liver weight, and testes weight were decreased, ammonia levels were higher, and the ratios of branched chain to aromatic amino acid (BCAA/AAA) were lower in the PCA group compared to the sham animals (P < 0.05). Since spleen weights correlated with portal pressure (P = 0.01), the PCA animals were then divided into those with preserved and those with low portal pressures based on spleen weight. The PCA group with preserved portal pressure had better growth, larger livers and testes, lower serum ammonia, and higher BCAA/AAA levels than the PCA group with low portal pressure; improvements associated with normal amounts of food intake and better food efficiency than the low pressure animals (P < 0.05 or better). Sham animals had no portosystemic shunting, while 100% shunting occurred in both PCA groups regardless of the portal pressure. In conclusion, preservation of portal pressure after portacaval anastomosis provides metabolic and nutritional benefits, which are independent of portosystemic shunting and associated with normal dietary intake and better preserved food efficiency.
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PMID:Preservation of portal pressure improves growth and metabolic profile in the male portacaval-shunted rat. 1235 33

Alpha1-antitrypsin deficiency (AATD) is a common hereditary disorder associated with high risk of developing pulmonary emphysema early in life and, to a lesser extent, chronic liver disease and cirrhosis. Among Northern Europeans and Northern Americans, more than 95% of individuals with emphysema associated with AATD carry the most frequent AAT deficient gene variants, PI*Z and PI*S. Rare AAT deficient variants account for 2-4% of AATD individuals. We extend the sequence data on AAT by characterizing a novel Null allele detected in 3 subjects: a carrier belonging to an Italian/Egyptian family and 2 members of a family originating from Southern Italy. The mutation raised on a M1 (Ala213) base allele and it is characterized by an A-->T transversion at exon III, nt 218, codon 259 (AAA-->TAA) (GeneBank accession number AY 256958). The transversion results in a premature stop codon (Lys259AAA-->Stop259TAA). The proposed nomenclature of Q0cairo is from the birthplace of the father of first recognized subject. Serum levels and isoelectric focusing of AAT were consistent with the presence of the Null variant.
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PMID:Identification of a novel alpha1-antitrypsin null variant (Q0Cairo). 1590 97


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