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)

The intrahepatic cholestasis is not an common syndrome, in particular way in people between 50 and 60 years of age. It is often unknown or confused, because of itching, with allergic or dermatologic diseases. The most frequent causes of intrahepatic cholestasis are primary sclerosing cholestasis, primary biliary cirrhosis and hepatic cirrhosis. The pathogenetic mechanism is the faulty secretion of bile and, more bile salts. The diagnosis is allowed by anamnesis, objective examination and, above all, biochemical markers of cholestasis, echography, TC, NMR and liver biopsy. Therapy consist of generic (hypolipidic diet, liposoluble vitamin and others) and specific (UDCA, SAMe) measures.
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PMID:[Intrahepatic cholestasis]. 926 12

NMR spectroscopy was used to examine hepatic metabolism in cirrhosis with a particular focus on markers of functional cellular hypoxia. (31)P and (1)H NMR spectra were obtained from liver extracts from control rats and from rats with carbon tetrachloride-induced cirrhosis. A decrease of 34% in total phosphorus content was observed in cirrhotic rats, parallelling a reduction of 40% in hepatocyte mass as determined by morphometric analysis. Hypoxia appeared to be present in cirrhotic rats, as evidenced by increased inorganic phosphate levels, decreased ATP levels, decreased ATP:ADP ratios (1.72 +/- 0.40 vs 2.48 +/- 0.50, p < 0.01), and increased inorganic phosphate:ATP ratios (2.77 +/- 0.48 vs 1.62 +/- 0.24, p < 0.00001). When expressed as a percentage of the total phosphorus content, higher levels of phosphoethanolamine and lower levels of NAD and glycerophosphoethanolamine were detected in cirrhotic rats. Cirrhotic rats also had increased phosphomonoester:phosphodiester ratios (5.73 +/- 2.88 vs 2.53 +/- 0.52, p < 0.01). These findings are indicative of extensive changes in cellular metabolism in the cirrhotic liver, with many findings attributable to the presence of intracellular hypoxia.
NMR Biomed 1999 Oct
PMID:31P and 1H NMR spectroscopic studies of liver extracts of carbon tetrachloride-treated rats. 1051 22

The oxygen limitation hypothesis states that hepatocyte hypoxia is the mechanism determining metabolic restriction in the cirrhotic liver. Therefore we studied markers of hepatocyte energy state and cellular hypoxia in livers of normal and cirrhotic rats before and after oxygen supplementation. Rats with carbon tetrachloride-induced cirrhosis and procedural control rats were exposed to either room air or a hyperoxic gas mixture for 1 h immediately before freeze clamping and perchloric acid extraction of liver tissue. Extracts were assessed by (31)P NMR and enzymatic assays. Livers from cirrhotic rats breathing room air showed a reduced ratio of ATP/ADP, an increased ratio of inorganic phosphate/ATP, and a trend toward an increased ratio of lactate/pyruvate compared with procedural control livers (ATP/ADP 1.73 +/- 0.35 versus 2.68 +/- 0.61, P <.05; P(i)/ATP 2.74 +/- 0.48 versus 1.56 +/- 0.26, P <.05; lactate/pyruvate 29.3 +/- 6.4 versus 22.5 +/- 7.4, P =.18). After supplementation with oxygen for 1 h, these ratios in cirrhotic livers approached control values. A variety of other metabolic markers affected by cirrhosis showed variable trends toward normal in response to oxygen supplementation, whereas minor trends toward an increase in ATP levels in control animals suggest the possibility of marginal oxygen limitation in normal livers. The data are consistent with the hypothesis that hepatocytes in cirrhotic livers have normal metabolic capacity but are constrained by a deficit in oxygen supply. Interventions aimed at increasing oxygen supply to the liver may have both short- and long-term therapeutic value in the management of cirrhosis.
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PMID:Acute oxygen supplementation restores markers of hepatocyte energy status and hypoxia in cirrhotic rats. 1077 39

Plasma glucose 2H enrichment was quantified by 2H NMR in patients with cirrhosis (n=6) and healthy subjects (n=5) fasted for 16 h and given 2H(2)O to approximately 0.5% body water. The percent contribution of glycogenolysis and gluconeogenesis to glucose production (GP) was estimated from the relative enrichments of hydrogen 5 and hydrogen 2 of plasma glucose. Fasting plasma glucose levels were normal in both groups (87+/-7 and 87+/-24 mg/dl for healthy and cirrhotic subjects, respectively). The percent contribution of glycogen to GP was smaller in cirrhotics than controls (22+/-7% versus 46+/-4%, P<0.001), while the contribution from gluconeogenesis was larger (78+/-7% versus 54+/-4%, P<0.001). In all subjects, glucose 6R and 6S hydrogens had similar enrichments, consistent with extensive exchange of 2H between body water and the hydrogens of gluconeogenic oxaloacetate (OAA). The difference in 2H-enrichment between hydrogen 5 and hydrogen 6S was significantly larger in cirrhotics, suggesting that the fractional contribution of glycerol to the glyceraldehyde-3-phosphate (G3P)-moiety of plasma glucose was higher compared to controls (19+/-6% versus 7+/-6%, P<0.01). In all subjects, hydrogens 4 and 5 of glucose had identical enrichments while hydrogen 3 enrichments were systematically lower. This reflects incomplete exchange between the hydrogen of water and that of 1-R-dihydroxyacetone phosphate (DHAP) or incomplete exchange of DHAP and G3P pools via triose phosphate isomerase.
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PMID:Sources of glucose production in cirrhosis by 2H2O ingestion and 2H NMR analysis of plasma glucose. 1263 4

The virally encoded NS3 protease is essential to the life cycle of the hepatitis C virus (HCV), an important human pathogen causing chronic hepatitis, cirrhosis of the liver, and hepatocellular carcinoma. The design and synthesis of 15-membered ring beta-strand mimics which are capable of inhibiting the interactions between the HCV NS3 protease enzyme and its polyprotein substrate will be described. The binding interactions between a macrocyclic ligand and the enzyme were explored by NMR and molecular dynamics, and a model of the ligand/enzyme complex was developed.
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PMID:Potent inhibitors of the hepatitis C virus NS3 protease: design and synthesis of macrocyclic substrate-based beta-strand mimics. 1535 76

In the absence of genetic hemochromatosis and systemic hemosiderosis, patients with cirrhosis can accumulate focal iron within regenerative or dysplastic hepatic nodules, commonly referred to as 'siderotic nodules'. Siderotic dysplastic nodules are premalignant lesions while siderotic regenerative nodules are a marker for severe viral or alcoholic cirrhosis. The relationship of hepatic iron deposition to hepatic cirrhosis and neoplasia has not been fully clarified. This article will review the current literature regarding selective iron accumulation in siderotic nodules in chronic liver disease, followed by a discussion of current MR imaging techniques for detection and characterization of these nodules.
NMR Biomed 2004 Nov
PMID:Iron-containing nodules of cirrhosis. 1552 93

The aim of this study was to assess the feasibility of using non-invasive MR elastography for determining the stage of liver fibrosis. Twenty-five consecutive patients who had liver biopsy for suspicion of chronic liver disease were included in the study. The stage of fibrosis on the biopsies was assessed according to the METAVIR scoring system from F0, no fibrosis, to F4, cirrhosis. MR elastography was performed by transmitting low-frequency (65 Hz) mechanical waves into the liver with a transducer placed at the back of the patients. The MR pulse sequence was a motion-sensitized spin-echo sequence, phase-locked to the mechanical excitation. The phase maps were processed to obtain shear elasticity and shear viscosity maps. The mean hepatic shear elasticity increased with increasing stage of fibrosis. The mean elasticity was 2.24 +/- 0.23 kPa in the 11 patients without substantial fibrosis (F0-F1 grades), 2.56 +/- 0.24 kPa in the four patients with substantial fibrosis (F2-F3) and 4.68 +/- 1.61 kPa in the 10 patients with cirrhosis (F4). The differences between groups were statistically significant (p <or= 0.05). The mean shear viscosity was significantly higher in the patients with cirrhosis (5.19 +/- 1.85 Pa x s) than in the patients without cirrhosis (2.39 +/- 0.86 Pa x s in F0-F1 and 2.27 +/- 0.38 Pa x s in F2-F3 patients). It is concluded that non-invasive MR elastography is a feasible method to assess the stage of liver fibrosis.
NMR Biomed 2006 Apr
PMID:Liver fibrosis: non-invasive assessment with MR elastography. 1652 Oct 91

Metabonomics has already been used to discriminate different pathological states in biological fields. The metabolic profiles of chronic experimental fibrosis and cirrhosis induction in rats were investigated using (1)H NMR spectroscopy of liver extracts and serum combined with pattern recognition techniques. Rats were continuously administered with thioacetamide (TAA) in the drinking water (300 mg TAA/L), and sacrificed on 1st, 2nd, and 3rd month of treatment. (1)H NMR spectra of aqueous and lipid liver extracts, together with serum were subjected to Principal Component Analysis (PCA). Liver portions were also subjected to histopathological examination and biochemical determination of malondialdehyde (MDA). Liver fibrosis and cirrhosis were progressively induced in TAA-treated rats, verified by the histopathological examination and the alterations of MDA levels. TAA administration revealed a number of changes in the (1)H NMR spectra compared to control samples. The performance of PCA in liver extracts and serum, discriminated the control samples from the fibrotic and cirrhotic ones. Metabolic alterations revealed in NMR spectra during experimental liver fibrosis and cirrhosis induction, characterize the stage of fibrosis and could be illustrated by subsequent PCA of the spectra. Additionally, the PCA plots of the serum samples presented marked clustering during fibrosis progression and could be extended in clinical diagnosis for the management of cirrhotic patients.
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PMID:Application of metabonomics on an experimental model of fibrosis and cirrhosis induced by thioacetamide in rats. 1711 14

It is often difficult to distinguish benign ascites from malignant ascites by conventional examination of ascitic fluid. Therefore, (1)H NMR spectroscopy of ascitic fluid specimens was explored as a one-shot experiment to identify potentially interesting metabolic indices that might help to differentiate between the two. Seventy ascitic fluid specimens (15 cytologically positive for malignant cells, eight cytologically negative for malignant cells but remaining suspicious for malignant ascites, and 47 due to liver cirrhosis) were subjected to (1)H NMR spectroscopy for quantitative estimation of 14 metabolites. Mean concentrations of the metabolites were compared with the Mann-Whitney U test. Multivariate discriminant function analysis was performed to determine important descriptors in the discrimination process. The sensitivity and specificity of the proposed model were compared with conventional methods using ascitic fluid protein and serum ascitic albumin gradient. Then, probable predictions for the doubtful cases were made using the proposed model. Patients with malignant ascites had significantly higher mean concentrations (microM) of beta-hydroxybutyrate (594 vs 61), lactate (5384 vs 2104), acetone (136 vs 69), and acetoacetate (122 vs 48) than patients with cirrhotic ascites, and significantly lower concentrations of glutamine (359 vs 615), citrate (62 vs 118), glucose (4933 vs 8411), tyrosine (44 vs 124), and phenylalanine (51 vs 93) (P < 0.05 for all). In the discriminant function analysis model, the best discrimination (P < 0.001) was achieved when beta-hydroxybutyrate, lactate, citrate and tyrosine were considered together as markers. Sensitivity and specificity of the proposed model, ascitic fluid protein and serum ascitic albumin gradient were found to be 100% and 97.9%, 53.3% and 76.6%, and 60% and 87.2%, respectively. The proposed model put five of the eight doubtful cases in the malignant group. This is encouraging and may provide useful information for clinical purposes.
NMR Biomed 2008 Jul
PMID:(1)H NMR spectroscopy of ascitic fluid: discrimination between malignant and benign ascites and comparison of the results with conventional methods. 1820 45

Chronic hepatitis B virus (HBV) infections may lead to severe diseases like liver cirrhosis or hepatocellular carcinoma (HCC). The HBV post-transcriptional regulatory element (HPRE) facilitates the nuclear export of unspliced viral mRNAs, contains a splicing regulatory element and resides in the 3'-region of all viral transcripts. The HPRE consists of three sub-elements alpha (nucleotides 1151-1346), beta1 (nucleotides 1347-1457) and beta2 (nucleotides 1458-1582), which confer together full export competence. Here, we present the NMR solution structure (pdb 2JYM) of the stem-loop alpha (SLalpha, nucleotides 1292-1321) located in the sub-element alpha. The SLalpha contains a CAGGC pentaloop highly conserved in hepatoviruses, which essentially adopts a CUNG-like tetraloop conformation. Furthermore, the SLalpha harbours a single bulged G residue flanked by A-helical regions. The structure is highly suggestive of serving two functions in the context of export of unspliced viral RNA: binding sterile alpha motif (SAM-) domain containing proteins and/or preventing the utilization of a 3'-splice site contained within SLalpha.
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PMID:Solution structure of stem-loop alpha of the hepatitis B virus post-transcriptional regulatory element. 1826 18


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