Effect of FUT-175 (nafamstat mesilate) on platelets in canine acute experimental pancreatitis.

In 1981, a new low-molecular-weight protease inhibitor, FUT-175 (nafamstat mesilate), was synthesized. Its preventive action against acute experimental pancreatitis (AEP) was detected. We studied the effect of FUT-175 on the blood count and aggregability of platelets in AEP in dogs. At 30 min after induction of AEP, the sensitivity to ADP increased more than two times in untreated animals. An evident decrease in platelet count of about 37% was noted in these dogs at 6 h after AEP induction. Treatment of AEP with FUT-175 prevented these changes. We assume that the positive effect of FUT-175 against AEP depends at least in part on its influence on platelet aggregation.

Effects of 1 gram oral or intravenous aspirin on urinary excretion of thromboxane B2 and 6-keto-PGF1 alpha in healthy subjects.

Aspirin inhibits cyclo-oxygenase, thus preventing prostanoids formation. After oral administration aspirin is hydrolysed to inactive salicylate partly within the gastrointestinal tract, partly during first pass in the liver, partly in the circulation by plasma esterases. Intravenous aspirin, in contrast, mainly undergoes plasma esterase-catalysed deacetylation. Six healthy male subjects were given 1 g aspirin orally and intravenously two weeks apart according to a cross-over randomized design. Whereas serum TxB2 generation reflecting platelet cyclo-oxygenase activity was suppressed by aspirin by both routes, urinary excretion of TxB2 and 6-keto-PGF1 alpha was not affected by oral aspirin, but was partially though significantly reduced by the i.v. drug. Drug disposition seems therefore to be essential in determining the "biochemical selectivity" of aspirin as related to platelet and renal prostanoids generation.

Clinical investigations on long-term activation of fibrinolysis by anabolic steroids.

The influence of anabolic steroids plus phenformin on the course of disease was studied in patients suffering from occlusive vascular diseases. In arteriosclerosis obliterans of the lower limbs the combined therapy led to a higher percentage of improvement than the control group showed. In coronary heart disease there was also a beneficial effect of this treatment. The drugs were found to exert beneficial clinical effects especially in patients with thrombophlebitis migrans and superficial thrombophlebitis. From the results of this study it is concluded that this therapy may be of clinical value in the treatment of patients with occlusive vascular diseases.

Plasma thromboxane B2 in haemodialysed patients.

Plasma thromboxane B2 (TXB2) concentration was measured in 7 cases of terminal renal failure before and after haemodialysis. The TXB2 levels were higher in the investigated group than in the control group (p less than 0.05). Haemodialysis induced a further increase in the TXB2 concentration. Increased thromboxane production may play a part in the pathogenesis of accelerated atherosclerosis in uraemic patients treated with chronic haemodialysis.

The effect of HR (O-Beta-Hydroxyethylo-Rutoside, Venoruton) on the deformability of erythrocytes in patients with arteriosclerosis obliterans of lower limbs.

Deformability of red cells and plasma levels of cAMP and cGMP were studied in patients with arteriosclerosis obliterans of lower limbs. Deformability of red cells and plasma levels of cAMP were found to be decreased in these patients. Venous injection of HR (Venoruton) in one dose (1,000 mg) to patients, led to an increase of red cell deformability and normalisation of cAMP plasma level. The plasma level of cGMP was not changed. The beneficial effect of HR in arteriosclerosis obliterans depends, first of all, on improving the deformability of red cells. The decreased deformability observed in arteriosclerosis seems to be a result of disturbances in the rate of spectrin phosphorylation of the erythrocyte membrane. By normalising the plasma level of cAMP HR had a considerable influence on the appropriate state of elasticity of the red cell membrane.

Platelet malondialdehyde and plasma thromboxane B2 formation in patients with obliterative arteriosclerosis of the lower limbs.

The platelet MDA and plasma TXB2 formation was studied in normal subjects and in patients with obliterative arteriosclerosis of the lower limbs. The increase in platelet MDA and plasma TXB2 formation could be found in these patients. It is concluded that these factors as well as the decrease in plasma cAMP level previously reported may play decisive role in the pathogenesis of occlusive arterial disease.

Prostacyclin-like, and kallikrein activity of amniotic fluid in pre-eclampsia.

Amniotic fluid from patients with pre-eclampsia was compared with samples obtained from normotensive controls with respect to the inhibiting effect on platelet aggregation (PGI2-like activity) and activating effect on the plasma kallikrein assay and Russell's viper venom test. After 39 weeks gestation, amniotic fluid from pre-eclamptic patients showed significantly less PGI2-like activity ( p less than 0.01) and significantly lower kallikrein levels (p less than 0.01) than that from normotensive controls. The study suggests that the biosynthesis and release of PGI2-like activity and kallikrein may be impaired in pre-eclampsia. In view of the association of pre-eclampsia with intravascular clotting, the highly significant reduction of PGI2-like activity seems important and appears to warrant a clinical trial of prostacyclin administration in this disorder.

An assessment of an amidolytic assay for factor VII in the laboratory control of oral anticoagulants.

A comparison has been made between the prothrombin time test using British Comparative Thromboplastin (BCT) and a chromogenic substrate assay for factor VII in the assessment of laboratory control of oral anticoagulants in short-term and long-term patients. Opportunity was also taken to compare the findings with parallel results obtained with the venous Thrombotest technique and a specific clotting assay for factor VII. There was good agreement between the amidolytic factor VII assay, using a method modified from Seligsohn et al (1978) with the Quick test using BCT and Thrombotest in 60 long-term patients. Tests in 53 patients within the first 3 weeks of starting oral anticoagulant administration gave less satisfactory agreement between the above amidolytic method and the conventional tests. In contrast, there was a good correlation between the two conventional tests in both groups and also between the clotting and amidolytic factor VII method. Although the results are an improvement on previous, less satisfactory correlations between the BCT prothrombin time method and amidolytic assays for factor II and X, the present study indicates the limitations of a specific clotting assay versus a broad spectrum extrinsic clotting test in oral anticoagulant control. While not warranting the routine use of the chromogenic assay for factor VII in place of the prothrombin time using BCT, the factor VII amidolytic assay offers a limited but dependable guide to dosage in long-term patients. The complexity of the technique in its present form militates against its adoption for routine anticoagulant control in hospital laboratories.

[Treatment of acute leukemias in adults. IV. Treatment results on 375 patients at 9 hematology centers]. / Leczenie ostrych bialaczek u doroslych. IV. Wyniki leczenia 375 chorych z 9 osrodków hematologicznych.

On the basis of standardized protocols of the therapeutic results of acute non-lymphoblastic leukaemias in adults sent to the Institute of Haematology in Warsaw from 8 haematological centres in Poland it was demonstrated that complete remission occurred in 34.4% of patients (129 out of 375 cases). The mean survival time of the patients treated intensively according to programmes I, II, III and IV 8.6 months, those of patients with complete remission - 13.5 months, patients without complete remission - 3.7 months. The most frequent cause of death (82.5%) were infections and/or haemarrhagic diathesis.

The effect of kallikrein on central effects of acetylcholine in rats receiving indomethacin and prostaglandin E1.

Kallikrein given in combination with acetylcholine (ACh) increased the central inhibitory action of ACh as measured in the Lat's test, duration of thiopental sleep and inhibition of electrogenic convulsions. Indomethacin aboished the potentiating effect of kallikrein on these actions of ACh, PGE1 did not play a significant role in the influence of kallikrein on the central action of ACh. However, inhibition of prostaglandin synthesis with indomethacin plays an important role in the interaction of kallilkrein and ACh.

The effect of prostaglandin E1 on central cholinergic mechanisms.

The influence of PGE1 and its precursor dihomo-gamma-linolenic acid on the central action of acetylcholine was studied. PGE, and dikomo-gamma-linolenic acid increased the depressive action of acetylcholine as evaluated with Lat's and thiopental sleeping time tests. PGE1 and its precursor diminished or eliminated the influence of acetylcholine on pentetrazol convulsions. Endogenous acetylcholine in excess inhibited hyperthermic effect of PGE1. The results show that PGE1 and its precursor may change the action of acetylcholine in the central nervous system.