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)

We have developed a convenient method combining fast protein liquid chromatography (FPLC) with sensitive radioimmunoassay (RIA) for thyrotropin-releasing hormone (TRH) to separate and identify TRH and its metabolite histidyl-proline diketopiperazine (CHP) and applied this to study inactivation of TRH by blood extracts from patients with liver cirrhosis (LC) and acute edematous pancreatitis (AP). Blood samples spiked with TRH and CHP were extracted by cold methanol and injected on a reverse-phase FPLC column. A linear gradient was applied for separation. Subsequent analyses of fractions by RIA for TRH revealed that only fractions 9-10 contained TRH. Separation by retention time (9.9 +/- 0.8 min for TRH, 10.5 +/- 0.6 min for CHP, mean +/- SEM) was highly reproducible. For degradation studies, pooled sera from patients with LC and AP were incubated with TRH and CHP for 60 min. Inactivation of TRH was less rapid in the presence of blood extract from LC patients than that from normal subjects or AP patients. CHP was more stable than TRH. These data suggest that activity of TRH-degrading enzymes is reduced in liver disease, whereas it does not appear to be altered in AP. Degradation of CHP does not closely reflect metabolic processing of its major precursor. This rapid and sensitive method may be applicable for further investigations on the metabolism of TRH in organic fluids.
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PMID:A fast protein liquid chromatography (FPLC) method for study of thyrotropin-releasing hormone (TRH) and its metabolite histidyl-proline diketopiperazine (CHP) in human blood: degradation in liver and pancreatic diseases. 812 15

Zinc treatment in liver cirrhosis is known to prevent a number of clinical symptoms. Previous studies have also indicated that Zn has a protective effect on the development of the clinical, biochemical and morphological manifestations of hepatic injury if administered simultaneously with the noxious agent. In this study, the protective effects of zinc treatment against the development of liver cirrhosis have been tested in cirrhotic rats treated by intragastric administration of CCl4. The development of morphological lesions has been investigated by means of standardized and comparable techniques, LM, TEM, SEM, microvascular casts and measurements of liver collagen content by colorimetric determination in paraffin embedded sections. LM and EM observations showed typical morphological features of cirrhosis in all CCl4 treated rats. In the same group of animals, the microvascular casts showed the development of the typical 'perinodular' branching and the various anastomoses of pre and post-sinusoidal vessels. Colorimetric evaluation has shown a significant increase in collagen content after CCl4 treatment. Qualitative and quantitative data of livers of CCl4 treated rats supplemented or not with zinc were significantly similar. In conclusion, zinc treatment influences biochemical parameters, but not the morphology of liver cirrhosis.
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PMID:Zinc supplementation in experimental liver cirrhosis: a morphological, structural and ultrastructural study. 821 81

Pharmacokinetic profile and urinary excretion of digitoxin and 4 metabolites were investigated in 9 patients with biopsy confirmed liver cirrhosis (median antipyrine clearance 20.0 +/- 5.4 ml/min; X +/- SEM) and were compared with that of 8 healthy volunteers (antipyrine clearance 36.9 +/- 4.9 ml/min) following intravenous and p.o. administration of 1 mg digitoxin. The kinetic parameters derived from the digotoxin plasma concentration time curve and from urinary recovery including total clearance of unchanged digitoxin did not differ significantly between both groups investigated. Renal clearance of digitoxin was 0.017 +/- 0.005 ml/min/kg in the patient group and 0.011 +/- 0.002 ml/min/kg in the volunteers (NS); it was 0.00340 +/- 0.00047 ml/min/kg and 0.00223 +/- 0.00039 ml/min/kg, respectively for digitoxigenin-bis-digitoxoside (NS), 0.00006 +/- 0.00001 ml/min/kg and 0.00016 +/- 0.00005 ml/min/kg for digitoxigenin-mono-digitoxoside (P < 0.05), 0.00041 +/- 0.00013 ml/min/kg and 0.00088 +/- 0.00032 ml/min/kg for digitoxigenin (P < 0.05), 0.00135 +/- 0.00049 ml/min/kg and 0.00113 +/- 0.00042 ml/min/kg for digoxin (NS). In conclusion, hydrolysis of digitoxin is altered in liver cirrhosis, whereby a significant reduction in the renal clearance and urinary recovery of digitoxigenin-mono-digitoxoside and digitoxigenin was seen in the present study.
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PMID:Digitoxin and its metabolites in patients with liver cirrhosis. 824 5

In patients with cirrhosis and ascites decreased renal blood flow might be related to the severity of liver disease but the relationship between the severity of cirrhosis and renal perfusion has not yet been established. Thus we measured renal, systemic and splanchnic hemodynamics in 63 patients with ascites and in 28 without ascites. When compared to patients without ascites, patients with ascites had lower renal blood flow (1,170 +/- 100 vs. 935 +/- 55 ml/min/1.73 m2; mean +/- SEM, p < 0.05) and renal perfusion pressure (78 +/- 2 vs. 72 +/- 1 mm Hg, p < 0.05 and higher inferior vena cava pressure (6.5 +/- 0.7 vs. 10.7 +/- 0.7 mm Hg, p < 0.05). Patients with ascites had significantly higher serum bilirubin concentrations, hepatic venous pressure gradient and lower serum albumin concentrations, indocyanine green (ICG) extraction than patients without ascites. Renal vascular resistance, glomerular filtration rate, mean arterial pressure, cardiac index and systemic vascular resistance were not significantly different between the two groups. By multiple regression analysis no significant correlation was found between liver tests (i.e., prothrombin time, serum bilirubin and albumin concentrations, ICG extraction), hepatic venous pressure gradient, cardiac index and systemic vascular resistance on the one hand and renal blood flow on the other. No significant correlation was found between glomerular filtration rate and liver tests. In conclusion, in patients with cirrhosis and ascites, renal hypoperfusion is not related to the severity of liver disease.
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PMID:Renal hemodynamics in patients with cirrhosis: relationship with ascites and liver failure. 828 84

Nocturnal glucose administration might prevent gluconeogenesis and concomitant protein loss due to hepatic glycogen depletion. In this study the effects of nocturnal oral glucose supplements on nitrogen metabolism were investigated in 8 cirrhotic patients and in 8 healthy controls. During the night, either polymeric glucose was given or water as placebo. In the patients with cirrhosis on placebo, nitrogen balance was not different from controls: -63 +/- 8 vs. -55 +/- 4 mg N/kg b.wt./9 h (mean +/- SEM). Cirrhotic patients had increased nocturnal protein turnover rates (measured with 15N-glycine) and increased early morning levels of free fatty acids (FFA), lactate, insulin, glucagon and growth hormone. After glucose, nitrogen balance improved by 36% in the cirrhotic group, with a decrease in protein turnover rates and a decrease in plasma levels of beta-hydroxybutyrate, urea and glucagon. In the controls, glucose had no effects on nitrogen balance, on protein turnover or on the hormone levels, except for reduced FFA and ketone body levels. These data show that nocturnal calorie supplements improve nitrogen balance during the night in cirrhotic patients but not in healthy controls. Long interprandial intervals should be avoided in cirrhotic patients.
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PMID:Nocturnal oral glucose supplementation. The effects on protein metabolism in cirrhotic patients and in healthy controls. 831 66

In an attempt to improve the prognostic capacity of Child-Pugh score in nonbleeding cirrhotics, 110 consecutive in-patients without gastrointestinal hemorrhage at admission were studied and followed up for 24 months or until death. Fifty-five of the 110 patients (50%) died during this period. Mean survival time was 18.8 +/- 1.4 months (mean +/- SEM). In addition to Child-Pugh score, eight variables, including anthropometric nutritional parameters, routine renal function tests, and alcoholism markers, were recorded at admission. The ability of these variables to improve the prognostic capacity of the Child-Pugh score was assessed with the proportional hazard Cox's regression procedure, using a stepwise method for covariate selection, after including the Child-Pugh score at the first step. Thus, in addition to Child-Pugh score (beta = 0.302), three variables were included in the final model: serum urea (beta = 0.113), MCV (beta = 0.027), and mid-arm muscle circumference (beta = -0.025). According to the contribution of each of these factors to the model, a prognostic index was obtained to estimate survival in the individual patient. An assessment of the predictive power of the model was made by means of a split-sample technique. The prognostic index described in this study may contribute to improve the selection of nonbleeding patients with advanced cirrhosis to receive specific therapies such as transplantation. However, its true clinical relevance will be established only by prospectively comparing its prognostic value with that of the Child-Pugh score in a new sample of patients.
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PMID:Routine tests of renal function, alcoholism, and nutrition improve the prognostic accuracy of Child-Pugh score in nonbleeding advanced cirrhotics. 843 45

Total plasma fatty acids were measured in 101 cirrhotic inpatients (64 men, 37 women, aged 64.3 +/- 1.2 (SEM) yr; range, 34-80) who were subsequently followed for survival for a mean of 14.8 +/- 1.0 months. Data on plasma fatty acids have been published elsewhere. Individual values of these variables were categorized in a binary fashion using the 5th or the 95th percentiles of a group of 44 well-nourished healthy controls (24 men, 20 women, aged 51.3 +/- 2.1 yr; range, 32-76) as the cutoff limit. Forty-nine patients died during follow-up (2-yr cumulative probability of survival, 52%). Deficiency of palmitate, dihomo-tau-linolenate, and arachidonate (values below the 5th percentile) were univariately associated with death (long-rank test). However, after a multivariate analysis (Cox's proportional hazards regression), only the existence of plasma arachidonate deficiency was included in the final model (beta, 0.62; relative risk, 1.86; 95% CI, 1.06-3.25; p < 0.05). We conclude that arachidonic acid deficiency significantly increases the mortality risk in patients with advanced liver cirrhosis.
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PMID:The relationship of plasma polyunsaturated fatty acid deficiency with survival in advanced liver cirrhosis: multivariate analysis. 848 Jul 37

Glutathione and amino acid concentrations were measured in arterial and hepatic vein plasma in four healthy volunteers and two patients with cirrhosis. There was no significant splanchnic efflux of glutathione (95% confidence limits, -0.501 to 0.405 mumol/min). After infusion of N-acetylcysteine (NAC) in a high dose (150 mg/kg body weight primer plus 15 mg/(h x kg BW), corresponding to treatment of acetaminophen overdose, there was no change in the splanchnic glutathione efflux (95% confidence limits, -0.531 to 0.375 mumol/min). NAC increased hepatic plasma flow rate from 0.90 +/- 0.531 min-1 to 0.97 +/- 0.11 (mean +/- SEM; p < 0.05). The effects of NAC treatment on plasma amino acids corresponded to an increased load on hepatic metabolic N conversion and transamination among nonessential amino acids. Splanchnic uptake of serine, alanine, cystine, isoleucine, and phenylalanine increased after NAC compatible with stimulated hepatic glutathione synthesis. In contrast to the rat, plasma glutathione in man probably originates mainly from extrahepatic tissues.
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PMID:No net splanchnic release of glutathione in man during N-acetylcysteine infusion. 851 1

To investigate the clinical significance of endothelin (ET), natriuretic peptides, and the renin-angiotensin-aldosterone system in pediatric liver transplantation, we measured plasma levels of ET, atrial and brain natriuretic peptides (ANP, BNP), aldosterone, and plasma renin activity in 18 patients (aged 0.5-12 yr; median 1 yr) undergoing living-related liver transplantation due to congenital biliary atresia and severe liver cirrhosis. Before transplantation, the plasma ET level (28.9 +/- 2.5 [mean +/- SEM] pg/mL) was increased compared with that of healthy children (10-18 pg/mL), but decreased during the anhepatic phase (22.5 +/- 1.6 pg/mL). It increased again after reperfusion and remained at high levels in the early postoperative period (postoperative day 3, 27.8 +/- 3.0 pg/mL). Plasma levels of ANP and BNP and aldosterone and plasma renin activity were also high before surgery. Plasma ANP and BNP did not change significantly during surgery. After transplantation, plasma BNP significantly increased, and plasma ANP tended to increase. Plasma aldosterone increased markedly during the anhepatic phase, although plasma renin activity decreased. After transplantation, plasma aldosterone and plasma renin activity both decreased to within normal levels. Mean arterial blood pressure increased gradually after reperfusion and surgery (postoperative day 3, 35.7 +/- 5.2% increase). No substantial differences in these variables occurred between the younger (< or = 1.0 yr, n = 9) and older patients (> 1.0 yr, n = 9). These results suggest that ET production in the cirrhotic liver is augmented and ET, natriuretic peptides, and the renin-angiotensin-aldosterone system all play some role in the circulatory regulation during perioperative periods of pediatric liver transplantation.
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PMID:Perioperative plasma concentrations of endothelin and natriuretic peptides in children undergoing living-related liver transplantation. 856 19

Intake of thioacetamide in drinking water causes liver cirrhosis in rats, which exhibit many changes similar to human disease. Nucleotides play an important part in major cellular functions, and recent studies suggest that dietary nucleotides may be considered 'semi-essential' nutrients in situations when an inadequate dietary supply may affect the growth of tissues with a rapid turnover rate. The aim of this study was to assess the effect of dietary nucleotides on lesions in thioacetamide-cirrhotic rats, and to calculate the proportion of mono and binucleated hepatocytes in different experimental groups. Rats were given cirrhosis by oral intake of thioacetamide in the drinking water (300 mg/l) for four months. One group was treated with a standard nucleotide free diet, and another group was treated with the same diet supplemented with 250 mg of nucleotides per 100 g of diet for one and two weeks. A striking reduction (mean (SEM)) in the proportion of binucleated cells was seen in thioacetamide-cirrhotic rats (4.8 (1.3) v 21.4 (1.0)), showing a change in the mitotic mechanism in focal lesions. Cirrhotic rats that consumed a semipurified diet supplemented with nucleotides during two weeks showed considerable histological regeneration of the injured liver. These animals had significantly higher proportion of binucleated cells than did animals at the beginning of the recovery period (8.2 (1.2) v 4.8 (1.3)). In the second week of recovery, both types of diet (F = 5.54, p < 0.05) and the previous administration of thioacetamide (F = 142.82, p < 0.001) had significant effects on the percentage of binucleated hepatocytes.
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PMID:Influence of dietary nucleotides on liver structural recovery and hepatocyte binuclearity in cirrhosis induced by thioacetamide. 880 Dec 8


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