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

Hyperammonemia is a well-recognized metabolic abnormality which occurs in cirrhotic patients with advanced liver dysfunction. We recently documented that hyperglucagonemia that occurs as a result of hepatic glycogen depletion may be responsible for this hyperammonemia by promoting gluconeogenesis to provide glucose as a fuel for functioning of several organ systems. Thus, hepatic glycogen depletion may be the initial process responsible for hyperammonemia. Since the glucose rise following intravenous glucagon administration is a reflection of hepatic glycogen breakdown, we studied the effect of glucagon (1 mg) injection on plasma glucose, insulin and ammonia levels after an overnight fast in cirrhotic patients and normal subjects. Glucose rise was significantly stunted, and ammonia rise was significantly greater in patients with advanced liver dysfunction as compared to normal subjects. Furthermore, the smaller the glucose increment, the earlier the ammonia rise. The smallest glucose responses were seen in the patients with the highest basal plasma ammonia levels. Finally, significant negative relationships were noted between the glucose response to glucagon administration (delta glucose) and the degree of liver dysfunction as reflected by Composite Clinical Laboratory Index, as well as basal ammonia and ammonia responses (delta ammonia) on the other. Therefore, this study suggests that hepatic glycogen depletion may be the initial event leading to elevated plasma ammonia concentrations in hepatic cirrhosis.
 ...
PMID:The association of hepatic glycogen depletion with hyperammonemia in cirrhosis. 330 64

1. In patients with cirrhosis of the liver and in healthy control subjects, the rates of nitrogen flux, protein synthesis and protein breakdown were studied, using a single oral dose of 200 mg of [15N]glycine as a tracer. The nitrogen flux through the amino acid pool was measured separately with both urinary ammonia and urinary urea as end products; the average value was used for further calculations. 2. Subjects were studied in the fed state, both on an adequate and a protein-restricted diet, and also in the fasting state. 3. The rates of protein synthesis were markedly increased in the patients, not only in the fed but also in the fasting state. Protein breakdown rates were increased in the patients in the fed state. 4. The nitrogen balance in steady-state conditions in the fed state was more positive in the patients, while their nitrogen loss in the fasting state was no higher than that of control subjects. 5. A hypothesis is put forward that the high protein requirements of cirrhotic patients could be caused by small and inadequate liver glycogen stores; due to these small stores, gluconeogenesis from amino acids will take place and lead to an extra amino acid loss even during short-term fasting. This increased amino acid loss could explain the elevated protein requirements in cirrhotic patients.
 ...
PMID:Elevated protein requirements in cirrhosis of the liver investigated by whole body protein turnover studies. 340 20

In a doubleblind cross-over placebo-controlled trial the efficiency of oral treatment with branched chain amino acids was investigated in 22 inpatients with liver cirrhosis. In all patients evidence of latent (subclinical) portalsystemic encephalopathy was obtained by using an extensive psychometric test programme. Patients received a defined diet of 35 cal/kg/day containing 1 g of protein. In addition, branched chain amino acids or casein in a dosage of 0.25 g/kg/day was administered in a cross-over fashion, each for 1 week. Semiquantitative nitrogen balance increased during both treatments, with a tendency towards a larger increase during branched chain amino acid treatment. At the same time ammonia concentration tended to decrease during branched chain amino acid treatment. Taking into account the cross-over design, significant improvements attributable to branched chain amino acid treatment could be demonstrated in psychomotor functions (line tracing, tapping, steadiness, auditory reaction time), attention (digit table), and practical intelligence (digit symbol, number connection test).
 ...
PMID:[Branched-chain amino acids in the treatment of latent porto-systemic encephalopathy. A placebo-controlled double-blind cross-over study]. 352 38

Alcohol, hepatitis B, and Non A Non B hepatitis were the main aetiologies of 124 patients with hepatic encephalopathy (HE) due to histologically proven liver cirrhosis. All had severe portal hypertension (PH) and usually increased inflammatory activity of the liver. In stage I (n = 27) 7.4% died, in stage II (n = 28) 14.3%, in stage III (n = 32) 50% and in stage IV (n = 37) 94.6%. Even in cirrhotics without PH, serum albumin, cholinesterase activity and prothrombin time (PT) were significantly decreased. But only in the case of PT did the magnitude of the decrease parallel the stage of HE. Hyperammonaemia and serum creatinine were increased in parallel with the stage of HE. Therefore, in liver cirrhosis a quotient derived from decreased PT and increased serum creatinine has a good prognostic value. Early diagnosis of HE is possible on the basis of writing tests and the determination of free or toxic ammonia.
 ...
PMID:The role of protein metabolism in 204 liver cirrhotics with and without hepatic encephalopathy. I. Clinical and general biochemical findings. 372 88

Thirty-seven patients, all with histologic evidence of cirrhosis and with a normal neurological examination and normal mental status were evaluated by psychometric testing for subclinical hepatic encephalopathy. They were all regarded as having well compensated cirrhosis, not requiring any treatment or dietary restrictions and they were working, and many of them driving. A group of 19 patients with a history of alcoholism, or medical disorders, but without clinical or biochemical evidence of cirrhosis, served as controls. They were matched by age, sex, education, and alcohol consumption. Investigations performed were an EEG, fasting arterial ammonia, liver biochemical tests and a series of verbal and performance psychometric tests. The EEG was abnormal in 3 (8.3%) of patients, the ammonia elevated in 17 (45.9%) of patients and 26 patients (70.3%) failed 2 or more psychometric tests, as compared to 2 (10.5%) of the control group. It is concluded that 2 out of 3 patients with stable, well compensated cirrhosis were suffering from subclinical hepatic encephalopathy and that impairment of performance rather than verbal skills occurred. The digital symbol test, trail test (number connection test) and block design tests readily identified the patients with subclinical hepatic encephalopathy. The implication of these observations in patients with cirrhosis, especially those working in mechanical or skilled occupations, needs consideration.
 ...
PMID:The diagnosis and prevalence of subclinical hepatic encephalopathy in apparently healthy, ambulant, non-shunted patients with cirrhosis. 374 89

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.
 ...
PMID:Elevated plasma ammonia level in hepatic cirrhosis: role of glucagon. 388 8

Branched chain amino acids have been recommended for the treatment of portosystemic encephalopathy based on the false neurotransmitter hypothesis. This hypothesis implies that by correction of the deranged amino acid pattern in the blood of cirrhotics, false neurotransmission and then portosystemic encephalopathy is improved. We conducted a double-blind crossover placebo-controlled trial in 22 inpatients with liver cirrhosis and obtained evidence of latent (subclinical) portosystemic encephalopathy using an extensive psychometric test program. Patients received a defined diet of 35 cal/kg X day containing 1 g of protein. In addition, branched chain amino acids or casein in a dosage of 0.25 g/kg X day was administered in a crossover fashion, each for 1 wk. Semiquantitative nitrogen balance increased during both treatments, with a tendency of a larger increase during branched chain amino acid treatment. At the same time ammonia concentration tended to decrease during branched chain amino acid treatment. Taking into account the crossover design, significant improvements attributable to branched chain amino acid treatment could be demonstrated in psychomotor functions (line tracing, tapping, steadiness, auditory reaction time), attention (digit table), and practical intelligence (digit symbol, number connection test).
 ...
PMID:Branched chain amino acids in the treatment of latent portosystemic encephalopathy. A double-blind placebo-controlled crossover study. 388 9

Evidence from several sources suggest that blood-brain transport of the large neutral amino acids (NAA) is abnormal in animals with a portacaval anastomosis (PCA) and in patients with liver cirrhosis and portal-systemic shunting and encephalopathy, but the underlying mechanisms are unknown. After PCA, the concentration of glutamine (Gln) in brain is markedly increased as a by-product of cerebral ammonia detoxification, and the rate of efflux of Gln from brain is also increased. The following studies were undertaken to clarify the relationships among plasma and brain concentrations of NAA after PCA in rats and to examine the relationship of brain Gln concentration to plasma and brain NAA concentrations. After PCA plasma phenylalanine, tyrosine and histidine were elevated and leucine, isoleucine and valine were lowered. In brain, phenylalanine, tyrosine, histidine and methionine were markedly elevated after PCA and their concentrations in brain far exceeded the concentrations in plasma. Analyses of single, partial and multiple correlations of plasma NAA ratios expressed as plasma competitor function (PCF), brain NAA and brain Gln showed significant correlations between PCF nd brain NAA in shunted rats. A better correlation was found between brain NAA and brain Gln. Correlation coefficients obtained from multiple correlation analysis equalled or exceeded those obtained in the partial correlation or in the single correlation, suggesting that the effects of PCF and brain Gln on brain NAA were separate and additive. Gln was shown to compete with other NAA for blood brain transport by inhibiting brain 14C phenylalanine uptake.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Relationship of brain glutamine and brain neutral amino acid concentrations after portacaval anastomosis in rats. 393 Feb 56

Fourteen patients with biopsy-proven alcoholic liver cirrhosis in a clinically stable phase but with compromised liver function entered the study, together with 10 control persons. All had normal creatinine clearance, and none received antibiotics or hormones. They ingested a diet containing 1 g of protein/kg body weight daily during the study. The fractional intestinal loss of newly synthesized urea, determined by a 14C-urea tracer method, was increased from 0.17 +/- 0.08 in controls to 0.26 +/- 0.08 in cirrhotics (mean +/- SD, P less than 0.02). Urea nitrogen synthesis rate, determined as urinary excretion rate, corrected for accumulation in the total body water and for fractional intestinal loss, was the same in controls and cirrhotics (26.1 +/- 3.8 and 22.1 +/- 6.8 mmol/h, respectively). The patients with cirrhosis had a significantly greater nitrogen balance than the control group (12.5 +/- 7.0 mmol/h versus 7.0 +/- 5.9 mmol/h; P less than 0.05). Furthermore, there was a positive correlation between intestinal loss and blood urea nitrogen concentration (r = 0.68, P less than 0.01) in patients with cirrhosis but not in controls. The increased endogenous ammonia load of cirrhotics corresponds to an extra protein intake of 30-35 g/day. In patients with cirrhosis prophylactic treatment with, for example, lactulose is rational before reduction in dietary protein.
 ...
PMID:Increased intestinal hydrolysis of urea in patients with alcoholic cirrhosis. 400 43

The EEG, grades of hepatic encephalopathy, and biochemical indices of 16 beagles with portacaval anastomosis were recorded throughout their lives and correlations between these parameters were investigated. The degree of deterioration of some biochemical indices, such as the ammonia concentration, glutamate oxaloacetate transaminase and alkaline phosphatase activities in the plasma, and percentage loss of body weight showed a progressive increase parallel to the severity of the hepatic encephalopathy (HE) grade (grading scale O-IV), but other biochemical indices such as the concentrations of aromatic or branched-chain amino acids, the molar ratio of branched-chain to aromatic amino acids, or the total protein concentration in the plasma did not show such relationship. The SW ratio, an index of the incidence of slow-waves in the EEG, was calculated from frequency distribution histograms which were obtained by frequency analyses of EEG recordings. A slight but significant correlation was found between the SW ratio and the plasma ammonia concentration. In addition, the SW ratio consistently increased with increase in the HE grade, although the SW ratio in HE grade IV was below the normal range for beagles. These results show that only the ammonia concentration in the plasma correlates with deterioration of the HE grade and of the SW ratio, suggesting that changes in ammonia concentration in the plasma should be of diagnostic value in assessing changes in mental state and the EEG in patients with liver cirrhosis. The importance of ammonia in pathogenesis of HE is stressed.
 ...
PMID:Correlation between electroencephalogram, hepatic encephalopathy grade, and biochemical indices in beagles with portacaval anastomosis. 400 21


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>