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Phenotype of urine sediment cells were studied in patients with bladder cancer depending on the cancer stage and recurrence prognosis. In T1N0M0 stage, the number of lymphocytes decreased, in T2N0M0 stage, the most pronounced shift was an increase in the number of erythrocytes. Irrespectively of the disease stage, we observed increased number of innate immunity cells and cells that inhibit antitumor immunity in the composition of the leukocyte fraction of urine sediment cells. At T1N0M0 stage, the epithelial-endothelial fraction was characterized by increased content of cells expressing CD13 marker (responsible for tumor growth and metastasis) and reduced number of cells expressing CD15 marker (responsible for intercellular adhesion). In patients developing relapse of bladder cancer, the number of lymphocytes was decreased in urine sediment cells and the number of epithelial and endothelial cells expressing CD13 marker was increased., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

Baseline density of intact lymphocyte beta2 adrenoreceptors (B max., 3H-DHA) was compared to dynamics of left ventricular hypertrophy (LVH) and frequency of essential hypertension (EH) complications within 7-9-year follow-up in 27 patients with EH stage II. No significant correlation was noted between B max and LVH changes. In a subgroup of 9 patients with initially very high B max overall number of complications reached 77.8% against 27.5%) (p<0.05) in control. These patients also developed acute myocardial infarctions more frequently (33.3% versus 0%, p<0.05). Such complications as strokes, coronary failure occurred with the same frequency. More extended trials are needed to infer on prognostic value of lymphocytic beta2-adrenoreceptor density.

Ethmozin (Moricizine HCl) and ethacizin are two class I antiarrhythmic drugs with different rate constants of interaction with the sodium channel. Computer simulation using the "guarded-receptor" model predicted that the combination of ethacizin and ethmozin should exert a greater decrease in excitability and conduction at short coupling intervals, but little effect at normal heart rates (HR). To test this prediction, we measured intraventricular conduction delay in canine hearts in vivo. In agreement with the model, the combination more potently prolonged the delay only at intervals < 600 ms as compared with ethacizin alone. Combination therapy was tested in 6 patients with idiopathic ventricular ectopic depolarizations (VEDs). Three patients were resistant to either ethmozin or ethacizin monotherapy, and three could not tolerate effective doses because of side effects. Quantitative continuous ECG monitoring showed that total VEDs in the resistant group decreased 0 and 17 +/- 13% for 400 and 800 mg/day ethmozin and 18 +/- 12 and 55 +/- 12% for 100 and 200 mg/day ethacizin, respectively. Combined therapy with ethmozin (400 mg/day) and ethacizin (100 mg/day) reduced the number of VEDs by 78 +/- 2% in these patients without side effects. In the "nonresistant" but intolerant group of patients, use of the combination allowed relief of symptomatic ectopy without side effects. A theoretical model correctly predicted an effective combination of class I antiarrhythmic drugs, one with "fast-off" and one with "slow-off" kinetics, which may provide a general rationale for choosing drug combinations.

Obsidan (propranolol) monotherapy was investigated for the effect on the density of lymphocytic beta2-adrenoreceptors (B max), the activity of lymphocytic homogenates adenylate cyclase (AC), plasma renin activity (PRA), aldosterone concentration (A) and plasma catecholamines (CA). Obsidan treatment brought about a 40% increase in B max without a significant changes in AC activity. Contrary to a significant fall in PRA, A and norepinephrine in plasma reduced insignificantly. Changes in B max correlated with its baseline level (r = -0.56, p < 0.01), PRA (r = 0.57, p < 0.01) and A level in plasma (r = 0.62, p < 0.01). No significant correlations appeared between hypotensive effect of the drug and drug-related changes in B max and AC activity, while PRA and A concentrations showed such dependence. B max and before treatment mass of the left ventricular myocardium correlated significantly (r = = 0.595, p < 0.01). A small decrease in the myocardial mass followed obsidan administration, being related to B max (r = = 0.497, p < 0.05). It is concluded that obsidan-induced changes in lymphocytic beta 2-adrenoreceptors correlate with alterations in the activity of renin-angiotensin-aldosterone system and myocardial hypertrophy dynamics.

The effects of prostaglandin E2 (PGE2) infusions on lymphocyte beta 2-adrenoceptor-dependent adenylate cyclase (beta 2ARAC) system were studied in 26 patients with resistant hypertension (RH). The density of beta 2-adrenoceptors and their affinity for 1-isoproterenol were measured with 125ICYP and adenylate cyclase activity was determined by alpha-[32P]AMP generation in mononuclear lymphocytes of RH patients before and 1, 7, and 14 days after the last PGE2 infusion. Plasma epinephrine and norepinephrine concentrations were analyzed by using HPLC. The resistance to the four-component drug therapy was overcome with PGE2 infusions in patients, leading to a decrease in lymphocyte beta 2-adrenoceptor density and an increase in beta 2-receptor affinity for catecholamines and in adenylate cyclase activation by stimulating agents. PGE2 infusions unchanged the sensitivity to antihypertensive drugs in patients resulting in an increase in lymphocyte beta 2-adrenoceptor density, a decrease in beta 2-receptor affinity for catecholamines and in adenylate cyclase activation.

Content of tocopherol and total antiradical activity of hydrophobic antioxidants were estimated in human blood platelets. Two hydrophobic antioxidants--tocopherol and ubiquinone were detected in hexane extracts of thrombocytes using thin-layer chromatography. After incubation of thrombocytes with N-ethyl maleimide content of malonyl dialdehyde was increased and of tocopherol--decreased, receptor-dependent increase of Ca2+ concentration in cytoplasm was potentiated, while the Ca(2+)-blocking effect of nitroglycerol was decreased. Nitroglycerol did not inhibit the N-ethyl maleimide effect on content of malonyl dialdehyde in blood platelets. Addition of exogenous vitamin E to thrombocytes did not affect the receptor-dependent increase of Ca2+ concentration. Ascorbic acid inhibited the receptor-dependent increase of Ca2+ concentration. The data obtained suggest that nitrates may be used more rationally in combination with antioxidants and/or inhibitors of cyclooxygenase.

During a prolonged (24-hour) intravenous administration in a dose of 126 mg, allapinine produced a stable pronounced antiarrhythmic effect in 90% of the patients with frequent premature ventricular contraction and adverse reactions in the central nervous system in 65% of the cases. However, the latter effect of allapinine is short-term and ceased independently without altering the infusion rate. More serious adverse effects (hypotensive reactions, proarhythmic effects) occurred in 4% of the cases.

The frequency-dependent effects on the intraventricular conduction through the dog heart in situ produced by two class 1 antiarrhythmic drugs, ethacizin and lidocaine, with different kinetic properties were investigated. Conduction delay was measured using stimulation of the His-bundle after pharmacologically induced atrioventricular (AV) block. Electrical events were derived from local epicardial bipolar electrograms at the base of the right ventricle. The stimulation program consisted of several 50-pulse trains with progressively shorter interstimulus intervals (ISI) separated by a l-s pause. Ethacizin (1.5 mg/kg) increased conduction delay by 30% at ISI of 1000 ms, and the effect was enhanced when ISI was shortened to 200 ms; l-s pauses did not significantly increase conduction velocity. Addition of lidocaine (12 mg/kg) strongly potentiated the ethacizin effect at ISI shorter than 300 ms without any noticeable increase in conduction delay at longer intervals. The major result was dramatic acceleration of conduction during the l-s pauses while both drugs were infused. With this combination, conduction delay after pause was shorter than with ethacizin alone, which is consistent with the competition of the drugs for the same binding site inside the sodium channel. Combination of two class 1 compounds in clinical practice may enhance their antiarrhythmic effects without adversely inhibiting normal impulse conduction in the heart. Computer-predicted data were in reasonable agreement with experimental results. The "guarded receptor" model, thus, can provide a simple method for predicting local anesthetic drug interactions in man.

Twenty eight males with dilated cardiomyopathy, 5 males with coronary heart disease concurrent with postinfarction cardiosclerosis, 4 males and 2 females with rheumatic heart disease were examined. The findings suggest desensitization of the cellular beta-adrenoreceptor complex in patients with circulatory failure, which appeared as lower beta-adrenoreceptor density with cardiac decompensation progression and impaired transmission of a hormonal signal in the cell, particularly in patients with dilated cardiomyopathy. Digoxin therapy let to an increase in beta-adrenoreceptor density with its initial decrease and to adenylate cyclase activity enhancement. The absence of a positive ++clinico-hemodynamic effect and time course of plasma catecholamine levels in some patients with severe circulatory failure during digoxin use, as well as no changes in the values of the beta-adrenoreceptor adenylate cyclase complex indicate that the abnormalities in beta-adrenergic regulation play an important role in the pathogenesis of refractoriness at the cellular level. Retention of forskolin's stimulant effect allows one to expect a significant positive therapeutic response to be shown with the usage of drugs whose load point is a catalytic subunit of adenylate cyclase.

Experiments with recording the time of intraventricular reentry of the canine heart by a special protocol of stimulation showed that the first-line antiarrhythmic agents having various kinetics, ethacizine and lidocaine, compete for their binding to the Na+ channels of cardiac fibers. As a result of this competition, additivity was not found in the effects of ethacizine, 1.5 mg/kg, and lidocaine, 12 mg/kg, on the rate of intraventricular conduction at heart rate under 180/min. At higher cardiac rhythm values, the total effects of the two agents on the conduction were observed. The experimental evidence confirm the results of mathematical modelling of the combined effects of ethacizine and lidocaine on the intraventricular conduction velocity, which were calculated on the basis of kinetic constants for binding and dissociation of the agents to Na+ channels. The findings show that when the two first-line antiarrhythmics having a substantially different kinetics were used in combination, their antiarrhythmic effect may be enhanced without their total effects on the rate of normal intraventricular conduction velocity reentry.

Nitroglycerin, isosorbide dinitrate and sodium nitroprusside, like nifedipine, were found to inhibit the receptor-provoked increase of cytosolic free calcium concentration in human platelets loaded with 2-[(2-amino-5-methylphenoxy)methyl]-6-methoxy-8-aminoquinoline-N,N,N',N' - tetraacetate. Sodium nitroprusside and nitroglycerin induced elevation of cyclic guanosine 3',5'-monophosphate content in platelets which correlated with their calcium-blocking activity. Methylene blue and epinephrine decreased the calcium-blocking effect and the influence of nitroglycerin on cyclic guanosine 3'-5'-monophosphate content, but failed to suppress the inhibitory effect of sodium nitroprusside. Ascorbic acid increased the calcium blocking effect of sodium nitroprusside and its influence on cyclic guanosine 3'-5'-monophosphate content, but did not alter the inhibitory effect of nitroglycerin. In order to evaluate the relationship between the mode of action of nitrates at cellular level and their vasodilatory effectiveness, we studied the circulatory response of the forearm to isosorbide dinitrate and the influence of nitroglycerin on free calcium concentration in the platelets in 10 patients with chronic heart failure. We established a significant positive correlation between the basal values for venous tone and its peak decrease after administration of the 10-mg dose of isosorbide dinitrate. A correlation was also found between the deviation of maximal decrease of venous tone by this dose of isosorbide dinitrate from the regression line (the relationship between the basal venous tone and its lowering by the drug) and mean inhibitory concentration values for nitroglycerin in blocking that proportion of the rise of calcium ion concentration in platelets due to blocking of the platelet-activating factor. Thus, nitrates, like calcium antagonists, inhibit the receptor-provoked calcium supply to the contractile system of the cells so neutralizing the effects of increased concentrations of vasoconstrictors. This suggests that the effectiveness of nitrates appears to be positively related to the contribution of receptor-induced increase of cytosolic free calcium concentration in vasoconstriction together with their capacity to raise cyclic guanosine 3',5'-monophosphate.

Ethacizine (2-carbethoxyamino-10 (3-diethylaminopropionyl) phenothiazine hydrochloride) has been administered in a daily dose of 150-200 mg for 8-10 weeks to 46 patients with diffuse psoriasis. The treatment has been effective in 84.8% of the patients. Late results, followed up over a year in 40 patients, are fine.

The effects of nitrates on Ca2+ increase and cyclic nucleotide content in human platelets were studied. Nitroglycerin, isosorbide dinitrate and sodium nitroprusside were found to inhibit the intracellular Ca2+ increase induced by the platelet activating factor, ADP and a stable thromboxane A2 analog--U46619. The inhibiting effect of sodium nitroprusside manifested itself at lower concentrations than those of nitroglycerin and isosorbide dinitrate. Nitroglycerin suppressed the Mn2+ entry into the cells and caused a 2-fold increase of the cGMP content which correlates with the calcium blocking activity. Methylene blue, a guanylate cyclase and glutathione reductase inhibitor, decreased the calcium blocking effect of nitroglycerin and its influence on the cyclic nucleotide content but failed to suppress the inhibitory effect of sodium nitroprusside. The data obtained suggest that the effects of nitrates on platelets are mediated by their influence on guanylate cyclase which leads to a cyclic nucleotide content increase and to a calcium blocking effect.

The article deals with the effect of the intravenous administration of streptodekase with heparin on the hemostatic system in patients with acute myocardial infarction. The data obtained are compared with the corresponding parameters in patients treated with native streptokinase. The advantages of the new thrombolytic drug over ordinary streptokinase are shown: a one-time administration of the whole therapeutic dose of streptodekase allows a significant simplification of the thrombolytic therapy scheme; streptodekase induces prolonged activation of fibrinolysis (up to 5-7 days) without any signs of its subsequent depression and with the minimum inhibition of blood coagulation. The specific selective influence of streptodekase on the fibrinolytic system helps to obviate hemorrhagic and thromboembolic complications characteristic of native streptokinase. In addition, low antigenicity and toxicity of streptodekase ensure the absence of any allergic and adverse side-effects in patients treated with the drug.

The effect of antiarrhythmic drugs on platelet calcium metabolism in peripheral blood has been examined. Anti-arrhythmic agents (ethmozine, ethacizine, quinidine, disopyramide, amiodarone), used extensively for the control of various heart rhythm disorders, as well as calcium antagonists (verapamil were shown to have a calcium-blocking property. It is demonstrated that the rate of reduction in the total number of extrasystoles in the presence of antiarrhythmic drugs is correlated to the magnitude of their in vitro calcium-blocking effect. It can be assumed that the action of antiarrhythmic drugs is in part mediated by their effect on calcium currents; at the same time, disorders of Ca2+ transport in myocardial cells are a cause of developing arrhythmias. The ability of antiarrhythmic drugs to affect platelet calcium ion currents may be used for preliminary assessment of the efficiency of antiarrhythmic drugs, used clinically to control heart rhythm disorders.

Allapinin after i.v. bolus infusion in a dose of 30 mg is relatively quickly eliminated from blood (in patients without congestive heart failure half-elimination period is 2.4 +/- 0.5 h and clearance is 79.0 +/- 8.9 l/h) which makes a good reason for its intravenous infusion according to the scheme "load dose + drop infusion". Marked heart failure in patients with acute myocardial infarction compared to patients without heart failure results in reduced elimination rate, decreased clearance, significantly increased plasma allapinin concentration which should be taken in account when choosing the regime of drug infusion. The elimination of allapinin is mainly metabolic and not renal (only about 17% of the drug is excreted with urine).

Epinephrine (E) and norepinephrine (NE) alone did not increase free intracellular Ca2+ ([Ca2+]i) in human platelets loaded with Quin-2 or Fura-2; however, they did potentiate the effects of vasopressin (VP), serotonin (S) and platelet activating factor (PAF). The synergism in [Ca2+]i increase was also obtained in the presence of VP together with PAF, S with PAF as well as VP with S. The effect of E or NE was blocked by yohimbine and phentolamine. Prazosin was less effective, while propranolol had no effect at all. Clonidine did not potentiate the effects of VP, S or PAF on [Ca2+]i; however, it did block the potentiation induced by E or NE. E potentiated the VP-induced 45Ca2+ uptake as well as VP-stimulated inositol 1,4,5-trisphosphate (IP3) formation. E alone did not change significantly the level of IP3 in platelets, nor did it influence the cyclic AMP level. The experimental results suggest that both Ca2+ influx and polyphosphoinositide breakdown underlie the mechanism of potentiation.

To study the process of dissolving polysaccharide carriers in the body used to prolong the action of drugs microspheric preparations of aldehyde-sephadexes of different degrees of oxidation containing I131-labelled covalently bound human serum albumin were synthesized. A radioisotope study of the rate of solution of the mentioned preparations injected by way of catheterization into the myocardial capillary network was conducted. The obtained carriers were shown to be harmless capable of prolonged retention of the bound protein at the site of injection, the rate of their solution in vivo and in vitro being nearly equal.

Extraction of 201TlCl3 diffusing into the heart tissue under conditions of its normal functioning and in the presence of ischemia was appraised on a model with isolated coronary perfusion of the myocardium by the dual-tracer method. From analysis of the discharge curve of the tracers used it is concluded whether or not microcirculation of the perfused area of the heart is uniform or heterogeneous. It was established that in myocardial ischemia, 201TlCl3 does not accumulate in the interstitium, which makes it possible to evaluate the zones with diminished inclusion of 201TlCl3 encountered in scanning of the heart as corresponding to diminished blood supply.

Clonidine-treated patients with essential hypertension demonstrated reliable positive correlations between echocardiographically determined signs of myocardial hypertrophy (thickness of left ventricular posterior wall and interventricular septum, left ventricular myocardial mass) and hormone-dependent increase in thrombocyte calcium concentration induced by ADP and TAF. Antihypertensive therapy was more effective in patients with relatively weak cellular effect of Ca-increasing hormone response having no signs of myocardial hypertrophy.

Loading of human platelets with quin2 considerably increases platelet activating factor (PAF)-induced 45Ca2+ uptake. 45Ca2+ binding in the absence of agonists remains unchanged. The data show that PAF stimulates calcium ion influx into platelets, since quin2 provides substantial additional buffer capacity for Ca2+ in the cytoplasm. PAF and prostaglandin endoperoxide H2 analogue, U46619, induce Ba2+ and Mn2+ entry. The entrance of these cations and the rise in [Ca2+]i are both blocked by cAMP elevation and activation of protein kinase C by phorbol ester which indicates a single mechanism for agonist-induced transport of all three cations into platelets. It is assumed that agonists stimulate Ca2+ entry through the receptor-operated channels.

We examine the heart's involvement in arterial hypertension, reporting on several studies of hypertensive patients showing that left ventricular myocardial mass is a significant prognostic indicator of essential hypertension and that left ventricular hypertrophy (LVH) correlates with an induced increase in Ca2+ concentration in platelets. We also consider the LVH variant of asymmetric hypertrophy and the role of the hypertensive heart in coronary insufficiency, and we speculate on the significance of the degree of LVH and asymmetric hypertrophy as risk factors for predicting cardiac complications of essential hypertension.

The authors analyze the efficacy of the treatment with combined streptodecase and heparin of patients with acute myocardial infarction as compared with the control receiving symptomatic therapy. The treatment contributed to rapid removal of pains, accelerated positive dynamics of the ECG, the recovery of the normal heart rhythm and conduction, and compensation for the symptoms of circulatory failure. In addition, the patients manifested less rarely the dissemination of the necrotic zone, the development of recurrent infarction, thromboembolism, heart aneurysm and rupture. Of great importance was the absence of hemorrhagic and allergic reactions, specific for therapy with native thromboembolic drugs. One-stage intravenous injection of all the therapeutic dose of streptodecase considerably simplifies the performance of thrombolytic therapy.

The usefulness of the thrombolytic therapy in diseases of the cardio-vascular system, complicated or caused by thromboses is beyond doubt. However, the existing medicinal forms of fibrinolytic enzymes possess a number of disadvantages which limit their use. To enhance the efficacy of thrombolytic therapy a streptokinase, named streptodekase, has been created and immobilized on a water-soluble matrix. Streptodekase was tested on the haemocoagulation system in 7 patients with thrombosis of the femoral artery or the branches of the pulmonary artery. It was seen that streptodekase causes a considerable and rapid increase of fibrinolysis without unwanted disorders in the blood coagulation and other side effects. The convenience in use and simplicity (the therapeutic dose of 3,000,000 units is administered in a single injection, intravenously and immediately), the safety and high specific activity permit one to think that the drug may be widely used.

The possibility of depositing in the myocardium drugs immobilized on modified Sephadex was studied. The method makes it possible to produce optimum local concentration of the drug with a predetermined rate of its detachment and has significant advantages over the commonly used methods for introducing drugs. Appraisal of a complex of data, including the findings of morphologic examination and analysis of the ECG and the curves of changes in the activity of CPK and hypoxanthine, has shown that intracoronary administration of 0.02 mg of Sephadex microspheres (approximately 20 000 microparticles) 20--40 mc in diameter per 1 g of dog myocardium has no harmful microembolic effect.

Comparative data of clinical, instrumental and coronarographic studies in 185 patients with ischaemic heart disease and stable angina pectoris are presented. It is concluded that in the evaluation of the severity of ischaemic heart disease along with the clinical data it behooves to give due consideration to the additional signs of chronic ischaemia of the myocardium: changes in repolarization on ECG at rest and after exercise, local disorders of the function of the left ventricle, disorders of lactic acid metabolism and cardiac rhythm.

It is shown that the diffusion capacity of the capillary channel diminishes in myocardial ischemia. In unchanged or increased capillary permeability this effect may only be explained by a functional shunt of the affected cardiac area. Intracoronary administration of a carrier of biologically active substances in the form of microspheres of modified Sephadex does not aggravate irregularity in the blood supply to the zone of ischemia, which is evidence of the adequacy of the organ reserves of the functional shunt in this situation.

Some methodical problems are discussed that are of practical importance for the performance of transvenous endocardial pacing of the heart in patients with acute myocardial infarction in whom the clinical course is complicated by an atrio-ventricular block. Some results of the employment of this method in 66 cases of acute myocardial infarction are presented. A set of criteria is suggested for controlling the proper position of the probe in the cardiac cavity, the most important approaches for the introduction of the probe are described, as well as the main reasons of ineffective cardiac pacing and its most common complications.