guanosine-monophosphate and Ascites

Nucleic acid reactive antibodies have been reported to inhibit various nucleic acid mediated functions in cell free systems. These antibodies were also shown to inhibit the growth of transformed cells in culture due to the high rate of endocytosis in transformed cells as compared to normal cells. In this report, we have tested the possibility of nucleic acid reactive antibodies inhibiting the growth of tumor cells in vivo. The life span of mice bearing Dalton's lymphoma ascites tumor cells was increased, when they were immunized with conjugates of guanosine-BSA, GMP-BSA and tRNA-MBSA complex before transplanting the tumor cells. A similar effect was also observed when mice were injected intraperitoneally with antibodies to guanosine or GMP along with the tumor cells. The specificity was ascertained, as immunization with non-specific antigens did not show any significant effect on tumor bearing mice. The results shows that nucleic acid reactive antibodies inhibit the growth of tumor cells in vivo.

Topics: Animals; Antibodies, Antinuclear; Ascites; Cell Division; Guanosine; Guanosine Monophosphate; Lymphoma, T-Cell; Mice; Mice, Inbred BALB C; Nucleic Acids; RNA, Transfer; Thymus Neoplasms; Tumor Cells, Cultured

Transjugular intrahepatic portosystemic stent-shunt (TIPSS) reduces the portal pressure gradient and leads to better control of ascites. The aim of this study was to evaluate (1) changes in renal handling of sodium following TIPSS and (2) the mechanism of these changes.. Prospective study.. Tertiary referral centre for liver diseases.. Eighteen patients with ascites undergoing TIPSS for recurrent variceal haemorrhage (16) (3 or more hospital admissions because of variceal haemorrhage whilst being treated endoscopically) or refractory ascites (2) were studied. Urinary sodium (UNa), creatinine clearance (CrCl), plasma renin activity (PRA), atrial natriuretic peptide (ANP), cyclic guanosine monophosphate (cGMP), Angiotensin II (AII) and lithium clearance (LiCl) were measured before and 3 months after TIPSS when portography was performed and the portal pressure gradient (PPG) also measured. All patients were haemodynamically stable and had received no diuretics for at least 1 week before blood sampling.. Improvement in ascites was achieved in all patients in whom TIPSS was inserted successfully (reduction in PPG to < 12 mmHg). PPG was reduced from a mean of 19 (+/-6) to 8.8 (+/-3.4) mmHg (P < 0.001). Urinary sodium and creatinine clearance improved significantly following TIPSS (P < 0.001, P < 0.001, respectively). PRA, All, cGMP and LiCl were abnormal before TIPSS and improved significantly following TIPSS (P < 0.007, P < 0.001, P < 0.001 and P < 0.01, respectively). ANP was not significantly different from normal controls and did not change significantly following TIPSS. Changes in UNa did not correlate with the Pugh score or the change in PPG.. The results of this study show that TIPSS is associated with significant improvement in UNa, CrCl, PRA, AII, cGMP and LiCl. The change in UNa following TIPSS was independent of the severity of underlying liver disease or the change in PPG.

Topics: Adult; Angiotensin II; Ascites; Female; Guanosine Monophosphate; Humans; Kidney Function Tests; Lithium; Liver Cirrhosis; Male; Middle Aged; Portasystemic Shunt, Transjugular Intrahepatic; Prognosis; Prospective Studies; Radioimmunoassay; Reference Values; Renin; Severity of Illness Index; Sodium

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)

Topics: Adult; Aged; Arginine; Ascites; Blood Platelets; Citrulline; Enzyme Inhibitors; Female; Guanosine Monophosphate; Heart Rate; Humans; Lipopolysaccharides; Liver Cirrhosis; Male; Middle Aged; Monocytes; Neutrophils; Nitric Oxide; Nitric Oxide Synthase; Platelet Aggregation; Platelet Aggregation Inhibitors; Stroke Volume; Tritium