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)

Thirty-seven patients with volume-retaining disorders (liver cirrhosis with ascites, n = 8; heart failure NYHA III-IV, n = 12; endstage renal failure, n = 17) and twelve healthy age-matched controls were given a small dose (33 micrograms) of hANF (human atrial natriuretic factor). We tested the resulting hemodynamic and renal effects as well as the effect on plasma cyclic GMP levels and compared them with the properties of platelet ANF receptors. The ANF injection evoked an increase in cyclic GMP plasma levels of 19.3 +/- 2.2 nM in healthy controls. This increase tended to be smaller in the cirrhosis group (15.5 +/- 3.3 nM) and in the heart failure group (16.8 +/- 2.3 nM) than in the dialysis group (20.5 +/- 2.5 nM). The invasion rates of cyclic GMP were comparable in all groups, but the evasion rates increased more in the heart failure and endstage renal failure groups (27.9 +/- 7.7 min and 26.1 +/- 3.4 min, respectively) than in the cirrhosis and control groups (14.9 +/- 1.9 min and 14.2 +/- 1.9 min, respectively). Patients with endstage renal failure and congestive heart failure showed a smaller decrease in diastolic blood pressure than controls and patients with liver cirrhosis. Renal actions of ANF were diminished in cirrhosis and heart failure patients. Binding capacities of platelet ANF receptors were higher in the control group (12.2 +/- 1.5 receptors/cell) than in the patient groups (cirrhosis, 7.8 +/- 1.2; endstage renal failure, 8.0 +/- 0.9; heart insufficiency, 8.0 +/- 1.0 receptors/cell), with no differences among the patient groups. Binding affinities were not significantly different. Correlation analysis showed that the relationship between the actions of ANF and the increases in plasma cyclic GMP levels is loose and cannot predict the hemodynamic or renal effects of exogenous ANF in a given patient. Although the behavior of plasma cyclic GMP levels fails to predict the responsiveness of the body to ANF in a given patient, it does reflect the differences between the patient groups and the control group. In contrast, we found no correlation between the properties of platelet ANF receptors and ANF action.
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PMID:Effects of a small bolus dose of ANF in healthy volunteers and in patients with volume retaining disorders. 216 5

To clarify the factor(s) responsible for changes in the plasma cyclic GMP concentration in liver diseases, we measured the plasma levels of cyclic GMP, along with cyclic AMP, in various clinical stages of chronic liver diseases and acute hepatitis. The level of cyclic GMP was found to increase significantly in the early stage of acute hepatitis, in the decompensated stage of liver cirrhosis, and in malignant diseases. In the former two states, it is postulated that decreased hepatic mass is responsible for the changes in the plasma cyclic GMP concentration. The retention rate of indocyanin green (ICGR15) was highly correlated with the plasma cyclic GMP level. The result suggests that the determination of plasma cyclic GMP is useful as an index of the reserve function of the liver in disease states.
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PMID:Deranged metabolism of cyclic nucleotides in liver diseases. 299 Nov 1

A study was made of the indices of lipid peroxidation (LPO)--conjugated dienes (CD) and diene ketones (D), cyclic nucleotides (CN)--cAMP and cGMP, prostaglandins (PG) E and F2 alpha in biopsy tissue of the liver in 55 patients with chronic hepatitis (CH) and liver cirrhosis (LC). LPO was determined by spectrophotometry, CH and LC--by a radioimmunoassay. In patients with CPH and CAH the indices of LPO and cGMP were normal, cAMP, PG and PGE/PGF2 alpha were raised. In a severe fast progressive liver lesion disorder of coordination activity of the cell membranous systems was characterized by a high LPO activity, a decrease in cAMP and relative deficit of liver PG.
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PMID:[Lipid peroxidation and the mechanisms of hepatocyte damage and protection in chronic hepatitis and cirrhosis]. 336 64

To investigate the prediction that urinary cGMP (UcGMP) and cAMP (UcAMP) excretion is altered in a manner consistent with unregulated cell growth in hepatocellular carcinoma (HCC), we studied 31 patients with this disease, 25 without apparent disease, 16 with various hepatic diseases, and 16 with nonhepatic neoplasms. Results were expressed as UcGMP excretion per 100 ml glomerular filtration because reduced creatinine excretion in patients with muscle wasting or renal dysfunction may spuriously elevate UcGMP. UcGMP excretion was elevated in 80% of patients with HCC, 75% of patients with hepatic disease and 68% of patients with other neoplasms. Mean values for UcAMP excretion did not differ significantly from normal values. Plasma and ascitic fluid cGMP concentrations in HCC and hepatic diseases were raised. These results support the hypothesis of a shift in cyclic nucleotide metabolism toward cGMP in malignant diseases. However, UcGMP measurement does not detect progression of cirrhosis to HCC.
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PMID:Cyclic nucleotides in biological fluids in hepatocellular carcinoma. 625 69

Urinary excretion of cyclic GMP (cGMP) and the plasma level of cyclic AMP (cAMP) were determined in patients with liver diseases. The urinary excretion of cGMP, expressed on the basis of creatinine excreted per day, was at significantly higher levels not only in primary hepatoma but also in liver cirrhosis, while the plasma level of cAMP was higher only in liver cirrhosis. Thus, the ratio of urinary cGMP excretion to plasma cAMP level in primary hepatoma was significantly higher than that in liver cirrhosis. In cirrhotic patients studied by catheterization, the level of cGMP in the hepatic vein was significantly lower than that in the superior mesenteric or portal vein, indicating the uptake of cGMP by the liver. Since cGMP excretion correlated with KICG both in liver cirrhosis and primary hepatoma, the increased cGMP excretion appeared to be explained by a reduced uptake of cGMP by the liver.
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PMID:Increased excretion of urinary cyclic GMP in primary hepatoma and preneoplastic liver. 629 71

Patients with cirrhosis and ascites have high plasma levels of atrial (ANP) and brain (BNP) natriuretic peptides, two cardiac hormones released by the atria and ventricles, respectively. We evaluated renal hemodynamics, sodium excretion, and intrarenal sodium handling (lithium clearance method) in seven cirrhotic patients with ascites and avid sodium retention before, during, and after the infusion of synthetic human BNP, at the dose of 4 pmol/kg.min for 1 hour, which has been shown to increase renal plasma flow, glomerular filtration rate (GFR), and sodium excretion in healthy subjects without affecting systemic hemodynamics. Plasma BNP levels were 7.31 +/- 0.85 pmol/L in baseline conditions, and increased to 33.60 +/- 2.96 pmol/L at the end of the infusion (P < .01 vs. baseline). Urinary excretion of guanosine 3',5'-cyclic monophosphate (cGMP) also significantly increased during the infusion, indicating stimulation of natriuretic peptide receptors by BNP. BNP administration did not modify renal plasma flow, GFR, sodium excretion or tubular sodium reabsorption to any appreciable extent. Arterial pressure heart rate, plasma norepinephrine, and plasma renin activity (PRA) where also unchanged, whereas plasma aldosterone concentration showed a significant, 35% reduction at the end of the postinfusion period, ruling out the possibility that BNP-induced vasodilation might be responsible for failure of the peptide to induce a natriuretic response. Overactivity of antinatriuretic factors is probably the main determinant of the blunted natriuretic effect of BNP in these patients.
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PMID:Blunted natriuretic response to low-dose brain natriuretic peptide infusion in nonazotemic cirrhotic patients with ascites and avid sodium retention. 748 83

To elucidate and to try to reverse the antinatriuretic mechanisms in liver cirrhosis, atrial natriuretic peptide (ANP) was given as a pharmacological bolus dose (2 micrograms per kg body weight) to 14 cirrhotic patients, and as a control to 14 healthy subjects. The nine patients with ascites had baseline values of glomerular filtration rate (GFR), effective renal plasma flow (ERPF) and blood pressure (BP) similar to controls. Their distal tubular fractional reabsorption of sodium (DFRNa), estimated by the lithium clearance technique, was higher than in controls, and so were plasma values of aldosterone (564 vs. 119 pmol l-1 medians), endothelin (1.23 vs. 0.63 pmol l-1), ANP (7.5 vs. 3.6 pmol l-1) and cyclic GMP (8.8 vs. 4.6 nmol l-1); p < 0.01 for all. The five patients without ascites had higher GFR and ERPF, and lower plasma angiotensin II than controls. After ANP injection, similar plasma levels of ANP and cyclic GMP were reached in all groups. Urinary sodium excretion rate increased in controls (0.23 to 0.52 mmol min-1, p < 0.01), while GFR increased (108 to 117 ml min-1, p < 0.05), and DFRNa decreased (93 to 89%, p < 0.01). In cirrhotics with ascites sodium excretion was unaltered (0.12 to 0.11 mmol min-1), and so was GFR (84 to 83 ml min-1). Proximal tubular fractional reabsorption of sodium increased after 90 min, whereas DFRNa decreased immediately (97 to 96%, p < 0.01) though less markedly than in controls. Sodium excretion increased in four of five patients without ascites (0.23 to 0.27 mmol min-1, medians). In patients with ascites, endothelin in plasma decreased after ANP (p < 0.05). Plasma levels of angiotensin II, aldosterone and vasopressin were unchanged in all groups. In conclusion, although hyper-reabsorption of sodium occurred in the distal rather than the proximal part of the nephron in cirrhotic patients with ascites, ANP had no natriuretic effect. This was most probably due primarily to the lack of increase of GFR and blunted inhibition of DFRNa, attributed to high aldosterone. The effect of ANP in suppressing the high endothelin did not seem to improve sodium excretion.
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PMID:Effects of high dose atrial natriuretic peptide on renal haemodynamics, sodium handling and hormones in cirrhotic patients with and without ascites. 756 29

Superoxide (O2-) and nitric oxide (NO) production by polymorphonuclear leukocyte (PMNs) and monocytes in patients with liver cirrhosis were evaluated. PMNs obtained from cirrhotic patients were less effective than those from controls in producing O2- after stimulation with opsonized zymosan, while they were more effective in producing NO, as shown by the inhibition of platelet aggregation and by the increase in cGMP content. NO synthase activity was higher in leukocytes from cirrhotic patients than in controls. A correlation was found between the cardiac index and the observed changes in the inflammatory cells.
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PMID:Changes in the production of nitric oxide and superoxide by inflammatory cells in liver cirrhosis. 761 30

In this work we analyze the renal and systemic factors involved in the sodium retention in two conditions: in extracellular volume depletion and in edema forming states, particularly liver cirrhosis with ascitis. In this paper we accept that the volume loss of body fluids stimulates the "effective arterial blood volume" (VAE). This term results from a decrease in the arterial blood volume secondary to a fall in cardiac output or a peripheral arterial vasodilatation. The reduction in the VAE stimulates: the high pressure baroreceptors (carotid sinus and aortic arch); the intrarrenal mechanisms, such as the yuxtaglomerular apparatus and the renin angiotensin aldosterone system; the sympathetic adrenergic system; the non osmotic release of antidiuretic hormone; prostaglandins (PGE1, Tromboxane) and endothelin; and inhibits the atrial natriuretic peptide. We also describe the sodium transport mechanisms along the nephron during physiological conditions and after volume depletion, and in edema formation states, specially hepatic cirrhosis with ascitis. We speculate that the intrarenal mechanisms are more important and persistent than the systemic mechanisms. It is possible that the sodium retention of these states might be the result of direct stimuli of the tubular sodium transport mechanisms in the different segments of the nephron, mediated by the co and counter transports, ATPase activity or by the second messengers cyclic AMP and cyclic GMP. The clonation and structural characterization of the different sodium transports may help us to establish, more precisely, the intracellular tubular mechanisms responsible for the tendency of the body to retain sodium. The amount of information generated in the future may help us to demonstrate, with more precision, the mechanisms responsible for the sodium retention and excretion in normal and pathological conditions, particularly the edema forming states such as cardiac failure, nephrotic syndrome and hepatic cirrhosis with ascitis.
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PMID:[Renal and extra-renal mechanisms of sodium and water retention in cirrhosis with ascites]. 777 18

Indirect evidence exists implicating vascular nitric oxide in the pathogenesis of arterial vasodilation in cirrhosis. In the current study, a coincubation assay to estimate the vascular nitric oxide production was developed and the nitric oxide production by arterial segments of cirrhotic and control rats was assessed. In the assay, measurement of reporter monolayer cell-associated cGMP levels allows the influence of nitric oxide released by arterial segments to be determined. RFL-6 cells served as reporter cells. Nitric oxide production was determined in thoracic aorta and mesenteric arteries of 22 control rats, 10 cirrhotic rats without ascites, and 12 cirrhotic rats with ascites. Basal and bradykinin-stimulated (10(-6) mol/L) intracellular content of nitric oxide-dependent cGMP was significantly higher in RFL-6 cells coincubated with aortic segments of cirrhotic rats with (21.3 +/- 3.6 pmol/10(5) cells, P < .05 and 44.7 +/- 7.0 pmol/10(5) cells, P < .025) and without ascites (15.3 +/- 3.0 pmol/10(5) cells, P < .05 and 43.2 +/- 7.6 pmol/10(5) cells, P < .05) than in those incubated with aortic segments of control rats (9.7 +/- 1.3 and 19.5 +/- 2.5 pmol/10(5) cells). RFL-6 cells exposed to bradykinin-stimulated mesenteric arterial segments of cirrhotic rats also showed increased cGMP content (ascitic: 2.73 +/- 0.31 pmol/10(5) cells, P < .005; nonascitic: 2.58 +/- 0.51 pmol/10(5) cells, P < .025) compared with cells exposed to control mesenteric arterial segments (1.28 +/- 0.15 pmol/10(5) cells). No differences between cirrhotic and control vessels were observed after endothelium denudation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nitric oxide production in arterial vessels of cirrhotic rats. 784 30


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