Cyclic guanosine 3 ',5 ' - monophospha-te [cGMP] in patients with different types of acute leukemia before and after chemotherapy

Plasma cyclic guanosine 3', 5'- monophosphate [cGMP] and urinary excretion of the nucleotide were measured in patients with acute leukemia. Ten patients with acute lymphoblastic leukemia [ALL], ten with acute myetoblastic leukemia [AML] as well as ten healthy controls were enrolled in the study. Samples were measured at presentation and after completion of inducttion chemotherapy. Statistically significant elevated levels of cGMP were found in leukemic patients compared to the controls. Highly significant difference was demonstrated in comparing pre-treatment to post-treatment levels of the nucleotide. A positive correlation was found between the level of plasma cGMP and the blast count in the bone marrow. There was no statistically significant difference between the levels of cGMP in different types of leukemia [ALL versus AML]. In patients who failed to attain complete remission, the level of cGMP remained high and it rised in those who relapsed even before blast invasion. It is concluded that cGMP is a good tumour marker in acute leukemia and it is useful in monitoring response to treatment or relapse

Kinins mediate the inhibition of atrial natriuretic peptide diuretic effect induced by pepsanurin

Pepsanurin is a peptidic fraction resulting from pepsin digestion of plasma globulins, that inhibits ANP renal excretory actions. We studied whether kinin-like peptides mediate the anti-ANP effect by testing if pepsanurin: 1) was blocked by the kinin B12 receptor antagonist HOE-140, 2) was produced from kininogen, and 3) was mimicked by bradykinin. Anti-ANP activity was assessed in anesthetized female rats by comparing the excretory response to two ANP boluses (0.5 mug iv) given before and after ip injection of test samples. Pepsanurin from human or rat plasma (1-5 mL/Kg), and bradykinin (5-20 mug/Kg), dose-relatedly inhibited ANP-induced water, sodium, potassium and cyclic GMP urinary excretion, without affecting arterial blood pressure. The same effect was exerted by pepsin hydrolysates of purified kininogen, whereas hydrolysates of kininogen-free plasma had no effect. HOE-140 (5 mug, iv) did not alter baseline, or ANP-induced excretion, but blocked the anti-ANP effects of pepsanurin. Histamine (15 mug/Kg) plus seroalbumin hydrolysates did not affect ANP response, despite inducing larger peritoneal fluid accumulation as compared with pepsanurin or bradykinin. We concluded that kinins cleaved from kininogen mediate the anti-ANP effects of pepsanurin by activation of kinin B2 receptors, independently of changes in systemic arterial pressure or peritoneal fluid sequestration.

approach to the role of nitric oxide in hyperdynamic circulation in liver cirrhosis

Circulatory abnormalities arising in cirrhosis increased cardiac output and, possibly, heart rate coupled with reduced systemic vascular resistance, and possibly arterial pressure could result from peripheral vasodilatation. The locally acting vasodilator nitric oxide has recently been implicated as a possible mediator in the vasodilatation observed in cirrhosis. To investigate this hypothesis, total of 51 patients with liver cirrhosis were recruited in the present investigation, 14 had hyperdynamic circulation [HDC] and 37 had no manifestations of HDC the study also included 20 completely healthy controls. In each participant, serum and urinary nitric oxide [NO], urinary cyclic guanosine monophosphate [cGMP] excretions, serum endotoxin and C-reactive protein were determined. The study revealed significantly increased levels of serum NO, endotoxin and C-reactive protein as well as urinary excretions of NO and cGMP in patients with cirrhosis compared with controls. Patients with HDC had significant increase of all bioindices expcept C-reactive protein. Significant positive correlation existed between urinary CGMP, urinary NO, serum NO, endotoxin C-reactive protein. These findings would indicate that bacterial endotoxin rather than cytokines induce NO synthase expression in vessel walls with sustained NO release. The released NO through activation of guanylate cyclase, leads to increased intracellular cGMP concentrations and induces vasodilatation and hypotension. Inhibition of NO synthesis in these patients could be achieved by reduction of endotoxaemia through sterilization of the intestine. This would result in restoration of sensitivity to vasoconstrictors and reverse the haemodynamic abnormalities in liver cirrhosis