UMLS:C0023890 - FACTA Search

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Query: UMLS:C0023890 (cirrhosis)
42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The monoclonal antibody-defined CAR-3 antigen is a new carcinoma associated marker which is expressed on a mucin-like molecule. Serum concentrations of CAR-3 were assayed in 181 patients with carcinomas of different organs, 20 patients with non-carcinomatous malignancies, 123 patients with inflammatory diseases and 150 healthy controls. Serum levels of CAR-3 were significantly increased in 51% of the patients with pancreatic carcinomas, in 60% of patients with biliary tract carcinomas and in about 15% of the patients with carcinomas of the digestive apparatus. Sera from patients with breast carcinomas were negative, as well as sera from patients with melanomas or sarcomas. CAR-3 values in samples from patients with chronic pancreatitis were constantly negative, as were samples from healthy donors. Significant concentrations of CAR-3 were detected in 20% of the sera from patients with acute pancreatitis and in 15% of the sera from patients with cirrhosis. Because of its high specificity for pancreatic carcinomas compared to chronic pancreatitis, CAR-3 seems a promising marker for distinguishing between neoplastic and chronic inflammatory diseases of the pancreas, whose differential diagnosis is difficult.
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PMID:The monoclonal antibody-defined CAR-3 antigen is a serological marker associated with pancreatic carcinoma. 297 86

An increased release of nitric oxide (NO), a powerful vasodilating agent, has been proposed to play a role in the pathogenesis of vasodilation and hyperdynamic circulation associated with advanced cirrhosis. We evaluated NO synthase (NOS) activity in peripheral leukocytes of 12 cirrhotic patients and 9 healthy subjects together with plasma endotoxin levels and systemic hemodynamic (by a noninvasive echocardiographic method). NOS activity was evaluated by (1) measuring the capacity of isolated polymorphonuclear cells (PMNs) and monocytes to convert [3H]arginine to [3H]citrulline; (2) measuring the ability of neutrophils and monocytes to inhibit thrombin-induced platelet aggregation and to increase guanosine 3'-5'-cyclic monophosphate content in coincubated platelets, an expression of NO release from these cells. Both neutrophils and monocytes from cirrhotic patients produced significantly higher amounts of [3H]citrulline than cells obtained from healthy subjects (P < .001 and P < .02 for neutrophils and monocytes, respectively) and were more effective than control cells in inhibiting platelet aggregation (P < .05 and P < .001, respectively for 2 x 10(6) cells) and in increasing guanosine 3'-5'-cyclic monophosphate content in coincubated platelets (P < .05 and P < .001, respectively). The anti-aggregating activity expressed by leukocytes has a pharmacological profile similar to that described for NO, because it increased after addition of superoxide dismutase, a superoxide anion scavenger, and markedly decreased after inhibition of nitric oxide synthesis with NG-monomethyl-L-arginine (L-NMMA) and NG-nitro-L-arginine-methyl ester (L-NAME). Cirrhotic patients had significantly higher plasma endotoxin levels (P < .001) and cardiac index (P < .01) when compared with controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased production of nitric oxide by neutrophils and monocytes from cirrhotic patients with ascites and hyperdynamic circulation. 748 72

In the present study, we have characterized the renal response to inhibition of endogenous nitric oxide (NO) synthesis [intravenous NG-nitro-L-arginine methyl ester (L-NAME) for 3 h] in anesthetized cirrhotic rats, with (ASC) and without (CIR) ascites, at doses that do not change blood pressure (BP). Administration of L-NAME induced opposite effects on water (UV) and sodium (UNaV) excretion in cirrhotic and control animals. Infusion of 1 microgram.kg-1.min-1 of L-NAME in CIR (n = 5) decreased renal plasma flow (RPF) at the end of the 3-h period, whereas UV, UNaV, and glomerular filtration rate (GFR) were unaltered. In contrast, infusion of L-NAME at 10 micrograms.kg-1.min-1 in six more CIR increased UV and UNaV significantly by the 1st h, without changes in BP or GFR, and these parameters remained elevated throughout the experiment. Infusion of 1 microgram.kg-1.min-1 in ASC (n = 6) did not change BP or GFR but significantly enhanced UV and UNaV after the 1st h. These effects were prevented by pretreatment with L-arginine (0.1 mg.kg-1.min-1) in another group of ASC infused with 1 microgram.kg-1.min-1 of L-NAME. These results indicate that, in ASC and CIR cirrhotic rats, inhibition of NO synthesis at nonpressor does improves renal excretion of sodium and water via a decrease in tubular reabsorption. NO is an important mediator of the renal excretory and hemodynamic alterations of experimental liver cirrhosis.
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PMID:Renal effects of nitric oxide synthesis inhibition in cirrhotic rats. 752 2

Arterial vasodilation is considered to be the key factor in the development of sodium and water retention leading to ascites formation in cirrhosis. To determine if nitric oxide (NO) is involved in the pathogenesis of arterial vasodilation in cirrhosis, we measured the concentration of cyclic guanosine monophosphate (cGMP), the second messenger of NO, in arterial tissue from rats with carbon tetrachloride-induced cirrhosis. Aortic cGMP concentration was markedly increased in cirrhotic rats, particularly in those with ascites (ascites, 826 +/- 70; no ascites, 597 +/- 48; controls, 331 +/- 25 fmol/mg, ANOVA F = 23.1, P < .0001), and correlated inversely with arterial pressure (r = -.56, P < .0001) and systemic vascular resistance (r = -.69, P = .014) and directly with cardiac index (r = .74, P < .01). The chronic administration of the NO synthesis inhibitor NG-nitro-L-arginine-methyl-ester (L-NAME) (10 mg/kg/day for 7 days) induced a marked reduction in aortic cGMP concentration in cirrhotic rats with ascites to similar values obtained in L-NAME-treated control rats (86 +/- 14 vs. 89 +/- 8 fmol/mg, respectively, NS), indicating that the high-aortic cGMP content in cirrhotic rats was caused by an increased NO synthesis. Mean arterial pressure after L-NAME treatment increased to similar values in both groups of animals. These results suggest that in cirrhosis there is an increased vascular production of NO that may play a role in the pathogenesis of arterial vasodilation.
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PMID:Increased aortic cyclic guanosine monophosphate concentration in experimental cirrhosis in rats: evidence for a role of nitric oxide in the pathogenesis of arterial vasodilation in cirrhosis. 776 8

We have evaluated the renal blood flow (RBF) response of cirrhotic rats to endothelium-dependent [acetylcholine (ACh)] and -independent [sodium nitroprusside (NP)] vasodilators. In anesthetized rats, ACh dose dependently increased RBF, but the response of the cirrhotic rats (n = 6) was significantly higher than that of the controls (n = 6). NP also increased RBF in a dose-dependent manner, but there were no differences between both groups. NG-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg i.v.) significantly reduced the responses to ACh in both groups, but those of the cirrhotic rats were still higher than those of the controls. In experiments performed in isolated perfused kidneys, preconstricted with phenylephrine, dose-response curves for ACh and NP were obtained in the presence of indomethacin. Both ACh and NP decreased renal perfusion pressure dose dependently, but only the response of the cirrhotic rats (n = 5) to ACh was significantly higher than that of the controls (n = 5). L-NAME (100 microM) significantly reduced the responses to ACh and increased those of NP and abolished the differences between groups, except at the high dose of ACh. These results demonstrate an elevated endothelium-dependent vasodilator response in the cirrhotic kidney, which is eliminated by combined prostaglandin and nitric oxide (NO) synthesis inhibition and suggest that increased intrarenal activity of NO may be contributing to the renal alterations of liver cirrhosis.
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PMID:Increased endothelium-dependent renal vasodilation in cirrhotic rats. 806 67

The contribution of nitric oxide to mesenteric arterial vasodilator responses was investigated in the isolated perfused mesenteric arterial bed of cirrhotic rats (carbon tetrachloride/phenobarbitone; n = 6). Age-matched (n = 9) and phenobarbitone-treated rats (n = 9) served as controls. Responses to the endothelium-dependent dilators acetylcholine and adenosine 5'-triphosphate (ATP) and the smooth muscle dilator (NO donor) sodium nitroprusside were investigated after tone was raised by continuous infusion of methoxamine, before and during infusion of the NO synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 30 mumol/L) +/- L-arginine (1 mmol/L). A significant hyporesponsiveness to methoxamine infusion in cirrhotic preparations (P < .05) was not fully corrected by L-NAME. There was no difference in the percentage vasodilator response to acetylcholine in the cirrhotic group compared with controls; L-NAME significantly and reversibly inhibited the dilator response in all groups. ATP elicited dose-dependent vasodilation that, in the absence of L-NAME, did not differ between the groups. By contrast, in the presence of L-NAME, ATP (5 x 10(-8) mol) produced pronounced, reversible vasoconstriction only in cirrhotic animals (P < .02). Vasodilatation attributable to sodium nitroprusside (5 x 10(-8) mol) was significantly attenuated in cirrhotic rats. The methoxamine data support the concept of mesenteric hyposensitivity to vasoconstrictor agents in cirrhosis that may be at least partly NO mediated. Increased NO activity in smooth muscle leading to decreased guanylate cyclase availability may account for the diminished vasodilator responses to sodium nitroprusside in cirrhotic preparations. The unchanged responsiveness to vasodilatation by acetylcholine (ACh) and the vasoconstriction to ATP observed during NO blockade in cirrhotic animals indicate that mesenteric endothelial NO is unchanged or possibly diminished.
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PMID:Mesenteric vasodilator responses in cirrhotic rats: a role for nitric oxide? 855 32

1. The effects of cirrhosis on mesenteric vascular reactivity were assessed in constantly perfused mesenteric arterial beds isolated from cirrhotic rats (carbon tetrachloride with phenobarbitone, n = 6), and from phenobarbitone-treated and untreated age-matched controls (n = 4,5). 2. At a constant flow rate of 5 ml min-1 there was no difference in basal perfusion pressure between the groups. Electrical field stimulation (EFS; 4-32 Hz, 90V, 1 ms, 30 s) of perivascular nerves caused frequency-dependent increases in perfusion pressure which were not different between the groups. Dose-dependent vasoconstrictor responses to exogenous noradrenaline (NA), methoxamine (an alpha 1-adrenoceptor agonist), adenosine 5'-triphosphate (ATP) and vasopressin were also similar between the groups. 3. The nitric oxide (NO) synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 30 microM) augmented constrictor responses to NA, EFS, methoxamine and vasopressin in all groups, and as shown for EFS and NA, this was reversed by L-arginine (300 microM). However, the maximum constrictor responses of cirrhotic preparations in the presence of L-NAME were significantly lower than those of both groups of control animals at the highest frequency of EFS (32 Hz) and highest doses of NA (0.15 and 0.5 mumol) and, compared to phenobarbitone-treated controls, methoxamine (5 mumol). Responses to ATP were significantly augmented by L-NAME only in the cirrhotic group. 4. A step-wise increase in perfusate flow to 10, 15 and 20 ml min-1 produced a broadly similar increase in perfusion pressure within each group. At increased flow rates, cirrhotic preparations were hyporesponsive to NA (15 nmol) compared to the phenobarbitone-treated animals but not the untreated controls. Glibenclamide (5 microM) or L-NAME (30 microM) had no significant effect on the relationship between flow and perfusion pressure or on responses to NA at the different flow rates. 5. We conclude that sympathetic neurotransmission is unchanged in cirrhosis. Endogenous NO is important in modulation of constriction in both normal and cirrhotic states. Changes in NO may occur in cirrhosis, although the role of this in hyporesponsiveness of cirrhotic preparations to NA at higher flow rates and to the greater potentiation of ATP-mediated constriction in the presence of L-NAME, together with the impact of factors such as changes in calcium and potassium channels, is not entirely clear.
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PMID:Vasoconstrictor responsiveness of the rat mesenteric arterial bed in cirrhosis. 873 49

Normalization of the increased vascular nitric oxide (NO) generation with low doses of NG-nitro-L-arginine methyl ester (L-NAME) corrects the hemodynamic abnormalities of cirrhotic rats with ascites. We have undertaken this study to investigate the effect of the normalization of vascular NO production, as estimated by aortic cyclic guanosine monophosphate (cGMP) concentration and endothelial nitric oxide synthase (eNOS) protein expression in the aorta and mesenteric artery, on sodium and water excretion. Rats with carbon tetrachloride-induced cirrhosis and ascites were investigated using balance studies. The cirrhotic rats were separated into two groups, one receiving 0.5 mg/kg per day of L-NAME (CIR-NAME) during 7 d, whereas the other group (CIR) was administrated the same volume of vehicle. Two other groups of rats were used as controls, one group treated with L-NAME and another group receiving the same volume of vehicle. Sodium and water excretion was measured on days 0 and 7. On day 8, blood samples were collected for electrolyte and hormone measurements, and aorta and mesenteric arteries were harvested for cGMP determination and nitric oxide synthase (NOS) immunoblotting. Aortic cGMP and eNOS protein expression in the aorta and mesenteric artery were increased in CIR as compared with CIR-NAME. Both cirrhotic groups had a similar decrease in sodium excretion on day 0 (0.7 versus 0.6 mmol per day, NS) and a positive sodium balance (+0.9 versus +1.2 mmol per day, NS). On day 7, CIR-NAME rats had an increase in sodium excretion as compared with the CIR rats (sodium excretion: 2.4 versus 0.7 mmol per day, P < 0.001) and a negative sodium balance (-0.5 versus +0.8 mmol per day, P < 0.001). The excretion of a water load was also increased after L-NAME administration (from 28+/-5% to 65+/-7, P < 0.05). Plasma renin activity, aldosterone and arginine vasopressin were also significantly decreased in the CIR-NAME, as compared with the CIR rats. The results thus indicate that normalization of aortic cGMP and eNOS protein expression in vascular tissue is associated with increased sodium and water excretion in cirrhotic rats with ascites.
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PMID:Nitric oxide synthase (NOS) inhibition for one week improves renal sodium and water excretion in cirrhotic rats with ascites. 942 86

1. The synthesis and release of nitric oxide may play a role in the pathogenesis of peripheral vasodilatation and hyperdynamic circulation observed in liver cirrhosis. In this work, we analysed the synthesis of nitric oxide by the lympho-mononuclear cells of peripheral blood from patients with chronic alcoholic and non-alcoholic liver disease and we identified the isoform of nitric oxide synthase involved in the increased nitric oxide synthesis. 2. Patients were classified following clinical and histological criteria in non-alcoholic cirrhotic, alcoholic cirrhotic and non-cirrhotic chronic liver disease. We studied clinical and analytical characteristics, haemodynamic parameters and endotoxin levels in these patients. 3. Cirrhotic patients showed an increase of cardiac output and a decrease of peripheral vascular resistance. These patients had higher levels of plasma endotoxin than those observed in the control group. N omega-Nitro-L-arginine methyl ester (L-NAME)-inhibitable nitrite production from mononuclear lymphocyte cells was higher in patients than in the control group, the highest levels being in non-alcoholic cirrhotic patients, and the lowest levels in patients with non-cirrhotic alcoholic liver disease. 4. Immunocytochemistry studies revealed a positive immunoreactivity for the inducible isoform of nitric oxide synthase in lympho-mononuclear cells that was more evident in non-alcoholic than in alcoholic cirrhotic patients. By Northern blot, inducible nitric oxide synthase mRNA expression was observed only in lymphomononuclear cells from non-alcoholic cirrhotic patients. 5. Our patients show a correlation between nitric oxide synthesis, endotoxin levels and haemodynamic parameters. 6. These findings indicate that lympho-mononuclear cell stimulation may play a role in elevated nitric oxide production in hepatic cirrhosis. Thus, this increased nitric oxide synthesis could be implicated in the pathogenesis of the haemodynamic disturbances frequently found in cirrhotic patients. This increase seems to be induced, at least in part, by activation of an inducible isoform of nitric oxide synthase.
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PMID:Increased nitric oxide synthesis and inducible nitric oxide synthase expression in patients with alcoholic and non-alcoholic liver cirrhosis. 985 62

Hyposensitivity to vasopressin is a well documented phenomenon in animals with portal hypertension and patients with cirrhosis subject to haemorrhage. Haemorrhage is associated with the endogenous release of bradykinin, which may subsequently stimulate the formation of nitric oxide (NO). The present study investigated the relative contribution of NO synthase (NOS) isoforms and the role of bradykinin in the pathogenesis of splanchnic hyposensitivity to a long-acting vasopressin analogue, glypressin, in rats with portal hypertension induced by partial portal vein ligation (PVL). At 14 days after the operation, systemic and portal haemodynamics were measured in stable or bleeding PVL rats receiving an intravenous infusion of glypressin (0.07 mg/kg). In the treatment groups, N(G)-nitro-L-arginine methyl ester (L-NAME; a non-selective NOS inhibitor), L-canavanine (a specific inhibitor of inducible NOS) or HOE 140 (a bradykinin B(2) receptor antagonist) was administered 45 min before the infusion of glypressin. In rats with a hypotensive haemorrhage, 4.5 ml of blood was withdrawn and 50% of the withdrawn blood was re-infused before the administration of glypressin or various inhibitors. Splanchnic hyposensitivity to glypressin was demonstrated in the haemorrhage/transfused PVL rats. The infusion of L-NAME elevated the mean arterial pressure in the bleeding PVL rats without the modulation of portal pressure. The addition of L-NAME or HOE 140, but not L-canavanine, significantly and similarly potentiated the portal-hypotensive effects of glypressin. It is concluded that constitutive NOS and bradykinin are responsible, at least partly, for the splanchnic hyposensitivity to glypressin observed in the early stages of the haemorrhage/transfused rat model of portal hypertension.
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PMID:Splanchnic hyposensitivity to glypressin in a haemorrhage/transfused rat model of portal hypertension: role of nitric oxide and bradykinin. 1109 89

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