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)

ADP-induced aggregation of normal washed platelets was measured by nephelometry in the presence of plasma high density lipoprotein (HDL) from normal subjects and from 30 patients with hepatic cirrhosis. HDL, at one-eighth of its plasma concentration, inhibited platelet aggregation; the effect of cirrhotic HDL (40% [SD 29%] inhibition) was significantly greater than that of normal HDL (16% [11%]). The mean apolipoprotein E content of cirrhotic HDL was significantly higher than that of normal HDL, and strongly inhibitory HDL contained twice as many apolipoprotein-E-rich particles as weakly inhibitory HDL. Inhibition of platelet aggregation was correlated with the apolipoprotein E content of HDL from patients with cirrhosis.
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PMID:Inhibition of platelet aggregation by abnormal high density lipoprotein particles in plasma from patients with hepatic cirrhosis. 256 8

An investigation of ADP-induced aggregation of thrombocytes in 62 patients with the portal hypertension syndrome has revealed pronounced functional alterations of blood platelets characterized by a lower aggregation rate, lower rate and degree of thrombocyte deaggregation. More profound alterations were found in patients with cirrhosis of the liver. It was established that the decreased rate and degree of the thrombocyte deaggregation with the growing aggregation rate, change of the aggregation into the irreversible form is a very dangerous portent of gastrointestinal bleeding.
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PMID:[Characteristics of thrombocyte aggregation properties in portal hypertension syndrome complicated by esophagogastric hemorrhage]. 263 47

The toxicity of uremic fluorescent substances (F-ure) in hemofiltrates of a dialysis patient on the respiration of rat liver mitochondria was studied in comparison with some fluorescent substances (F-cir) in a cirrhosis urine. These substances found in both the body fluid of chronic disease were fractionated by hydrophobic HPLC. And the characteristic of (1) F-ure and (2) F-cir was as follows: the hydrophobicity based on Sasagawa's constant, (1) 1.1 approximately 1.3 & (2) 1.8; lambda max in UV spectrum, (1) 231, 356 nm & (2) 220 approximately 230, 290 nm; Em in fluorescence, (1) 461 nm & (2) 361 or 504 approximately 7 nm. When F-ure was added into mitochondrial respiratory medium, the respiration of succinate (State 4) decreased about a half in the presence of phosphate and succinate/ADP respiration (State 3) was much suppressed. And about a quarter of this suppression was released by an uncoupled (SF-6847), whereas F-cir on the state 3 respiration showed to be stimulative effect in like manner of uncoupler. The toxicity of uremic fluorescent substances on cellular energy generation could be demonstrated by decreased respiration of mitochondria.
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PMID:[Inhibitory effect of uremic fluorescent substances on the cellular energy generation]. 274 95

Energy-rich phosphagens, water, and electrolytes were determined in skeletal muscle biopsy specimens from five elderly women and five elderly men with moderate liver cirrhosis. At the time of the study the patients were in their usual condition without evidence of deterioration of the disease. When compared with findings in apparently healthy subjects of similar age, the distribution and level of electrolytes and water were within normal limits in the female patients. The male patients showed increased contents of muscle water, and Mg2+ was reduced. The values calculated for the intracellular concentration of K+ and Mg2+ were also below normal. The pattern and levels of energy-rich phosphagens were abnormal in all but one female patient. As a general finding, ATP and the total level of adenine nucleotides were markedly reduced, as were phosphocreatine, the ATP/ADP ratio, and the energy charge potential.
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PMID:Muscle biopsy studies in patients with moderate liver cirrhosis with special reference to energy-rich phosphagens and electrolytes. 671 37

Twenty eight patients affected by liver cirrhosis were studied in comparison with 44 control subjects, matched for age. The following parameters were carried out: a) platelet aggregation (by Born's method) induced by increasing concentrations of ADP and epinephrine; b) PF3 ( Spaet - Cintron method) and antithrombin III, aPTT, prothrombin ratio, fibrinogen, platelet count. Platelet aggregation and availability of PF3 are lower in cirrhotic patients, suggesting an intrinsic defect of platelets. Moreover prolongation of aPTT and prothrombin ratio, lower levels of antithrombin III, fibrinogen and platelet count were detected.
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PMID:[Platelet aggregation and various coagulation parameters in liver cirrhosis]. 672 55

To assess the nature of the hemostatic abnormalities associated with chronic liver disease, we have simultaneously evaluated the kinetic of radiolabeled platelets, fibrinogen, and plasminogen, together wit tests of platelet and fibrinogen function, and coagulation factors in 60 patients with documented, severe but stable cirrhosis of the liver. The mean platelet survival was substantially reduced (5.8 +/- 1.7 days compared with 9.5 +/- 0.6 days in normals, p less than 0.0001) and splenic sequestration of platelets was increased (mean recovery was 47% +/- 18 vs. 65% +/- 5 in normals, p less than 0.0001). Nevertheless the mean platelet count was nearly normal because platelet production was increased nearly twice normal values (mean turnover was 64,000 +/- 33,000 platelets/microliter/day; p less than 0.0001). The mean rate of fibrinogen removal was shortened (p less than 0.0001) and fibrinogen turnover increased about 20% (p = 0.008) while the mean fibrinogen concentration was not different from the results in normal control subjects (p = 0.212). Autologous and homologous fibrinogen disappeared from the circulation at equivalent rates (r = 0.751; p = 0.008), indicating that fibrinogen from cirrhotic patients was not kinetically different from normal fibrinogen. The mean plasminogen survival was significantly shortened (p less than 0.0001), but the mean plasminogen turnover was not increased (p = 0.388). Thus the plasminogen concentration was reduced (p less than 0.0001). For platelets, fibrinogen, and plasminogen, the production rate was the most important determinant of the concentration in the circulation. The administration of heparin to cirrhotic patients improved the survival of fibrinogen but not of platelets. LeVeen valve implantation generally resulted in parallel shortening of both the platelet and fibrinogen survivals and concentrations. Platelet function as assessed by template bleeding time, platelet retention by glass bead columns, and aggregation induced by ADP, epinephrine, and collagen was normal. Fibrinogen determinations by the Clauss and Jacobsson techniques were equivalent, indicating that the ability to polymerize fibrin monomer was not detectably altered. Sixty percent of patients had an abnormal prothrombin time and half that number had a prolonged partial thromboplastin time. Although most patients had a modest decrease in the prothrombin complex coagulation factors, fibrin degradation products were, in general, not elevated in the circulation. The wide range of values observed suggests that a number of different and complex processes may be ongoing in different patients. Overall, the kinetic data suggest that platelets are initially consumed, perhaps on incompletely endothelialized endovascular surfaces in the liver, and that fibrin subsequently forms secondary to local stasis. The absence of increased production of fibrinogen and plasminogen despite shortened survival times reflects the reduced capability of the cirrhotic liver to increase protein synthesis.
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PMID:Kinetic and functional studies of platelets, fibrinogen, and plasminogen in patients with hepatic cirrhosis. 706 18

To assess whether aortic vessels of rats with cirrhosis and ascites possess an enhanced vascular response to endothelium-derived, nitric oxide-dependent vasodilators, we performed relaxation studies in isolated aortic rings of 21 control rats and 24 rats with carbon tetrachloride-induced cirrhosis and ascites. We carried out studies after contracting the vessels with norepinephrine. We measured endothelium-dependent vasodilator response by administering increasing concentrations of acetylcholine (10(-6) to 10(-2) mol/L) and ADP (10(-7) to 10(-4) mol/L). We evaluated endothelium-independent response by giving increased concentration of sodium nitrite (10(-5) to 10(-2) mol/L). The maximal absolute tension developed in response to norepinephrine was significantly decreased in cirrhotic rings (816 +/- 72 mg, p < 0.025) compared with control (1,425 +/- 75 mg) rings. Dose-response curves for endothelium-dependent vasodilators were shifted to the left in aortic rings of cirrhotic rats, and EC50 for acetylcholine and ADP were significantly decreased in cirrhotic (0.8 +/- 0.15 mmol/L and 0.42 +/- 0.16 mumol/L, p < 0.025 and p < 0.01, respectively) than in control rings (1.91 +/- 0.33 mmol/L and 3.09 +/- 0.82 mumol/L). In both acetylcholine- and ADP-stimulated vessels, differences between cirrhotic and control rings disappeared after nitric oxide synthesis inhibition with N omega-nitro-L-arginine (10(-4) mol/L). No difference in the relaxing effect of sodium nitrite was observed between cirrhotic and control rings. These results therefore demonstrate for the first time enhanced in vitro vascular responsiveness to nitric oxide-dependent vasodilators in rats with cirrhosis and ascites, giving further support to the concept that nitric oxide activity is increased in cirrhosis.
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PMID:Increased nitric oxide-dependent vasorelaxation in aortic rings of cirrhotic rats with ascites. 765 70

8-epi-Prostaglandin (PG) F2alpha may be formed by cyclooxygenases 1 and 2 or by a free radical catalyzed process as an isoprostane. Concentrations of 8-epi-PGF2alpha in the range 1 nM to 1 microM induce a dose-dependent increase in platelet shape change, in calcium release from intracellular stores [Ca2+]iand in inositol phosphates; it also causes irreversible platelet aggregation, dependent on thromboxane generation, when incubated with subthreshold concentrations of ADP, thrombin, collagen, and arachidonic acid. Much higher concentrations of 8-epi-PGF2alpha (10-20 microM) alone induce weak, reversible aggregation. Although these effects are prevented by pharmacological thromboxane receptor antagonists, they are unlikely to be mediated by thromboxane receptors. Thus, 8-epi-PGF2alpha does not compete for binding at the stably expressed placental or endothelial isoforms of the thromboxane receptor or for binding of thromboxane ligands to human platelets. Furthermore, the response to 8-epi PGF2alpha exhibits structural specificity versus 8-epi PGF3alpha and PGF2alpha. Concentrations in the range that evoke its effects on platelets do not desensitize the aggregation response stimulated by thromboxane or PGH2 analogs. Unlike primary prostaglandins, which are rapidly metabolized to inactive products, 8-epi PGF2alpha circulates in plasma. However, the systemic concentrations found in healthy volunteers (median 48 pmol/liter) and in patients with hepatic cirrhosis (median 147 pmol/liter), a syndrome of oxidant stress in vivo, fall well below those which modulate platelet function. 8-Epi PGF2alpha may amplify the response to platelet agonists in syndromes where oxidant stress and platelet activation coincide. Despite blockade by thromboxane antagonists, 8-epi PGF2alpha does not activate either of the thromboxane receptor isoforms described in platelets. Activation of a distinct receptor would be consistent with the enzymatic formation of 8-epi PGF2alpha by cyclooxygenases. However, incidental activation of such a receptor by systemic concentrations of 8-epi PGF2alpha is unlikely to occur, even in syndromes of excessive free radical generation in vivo.
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PMID:Local amplification of platelet function by 8-Epi prostaglandin F2alpha is not mediated by thromboxane receptor isoforms. 866 15

A defect in hemostasis has been repeatedly reported in patients with cirrhosis. However, the nature of this defect has not been fully characterized. We explored adhesive and cohesive functions of platelets from cirrhotic patients at different stages of disease development. The response of platelets to standard activating agents was tested by aggregometric procedures. The interaction of platelets with subendothelial components was explored in a perfusion system in which blood was exposed (shear rate, 800/s; 10 minutes) to denuded segments of rabbit aorta. Platelet interactions in these perfusions were analyzed morphometrically. Results were always compared with those obtained in similar studies using blood obtained from healthy subjects. Aggregation studies showed abnormal responses for single or several agonists. Abnormalities in aggregation were more evident in patients with severe disease (Child-Pugh class C), although they occasionally were abnormal for single agonists (ADP or U46619) in patients with less severe disease (Child-Pugh classes A or B). All the patient classes showed impaired platelet-subendothelial interactions (P < .01 vs. healthy subjects) that were not justified by the relative thrombocytopenia present in the more severely affected patients. Experimental increases in hematocrit in patients at stages B and C did not improve platelet-subendothelial interactions. Platelets from cirrhotic patients interact defectively with subendothelial components under flow conditions. The adhesion defect is more evident and consistent than the aggregation defects and may already be present in patients with mild liver failure. This adhesion defect may contribute to the defective hemostasis observed in cirrhotic patients.
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PMID:Existence of a platelet-adhesion defect in patients with cirrhosis independent of hematocrit: studies under flow conditions. 890 88

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.
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PMID:31P and 1H NMR spectroscopic studies of liver extracts of carbon tetrachloride-treated rats. 1051 22


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