[Hemodynamic effects of the synthetic analogue of endogenous nitric oxide (II) donors a dinitrosyl iron complex in hypertensive patients with uncomplicated hypertensive crisis].

AIM: To examine the antihypertensive effect of the synthetic analogue of the endogenous nitric oxide donors in patients with grades 2-3 hypertension and uncomplicated hypertensive crisis (HC). SUBJECTS AND METHODS: The study included 30 male patients aged 35 to 73 years (mean age 55.5 ± 10.8 years). All the patients had grades 2-3 essential or secondary hypertension. Thirteen (43.3%) patients were observed to have signs of HC; 17 (56.7%) patients had persistent blood pressure (BP) elevation. A dinitrosyl iron complex was injected in a dose of 1.5 or 3 mg per kg of body weight. The purpose of its administration was to lower BP by at least 20% of its baseline level. RESULTS: No significant side effects associated with the administration of the test drug were recorded when the clinical trial protocol was implemented. All the patients reported fever and facial hyperemia during and 10-20 minutes after injection. They all (100%) showed efficient blood pressure reduction of at least 20% of the baseline level. Blood pressure changes were similar when the agent was administered in doses of 1.5 or 3 mg/kg. At 6-8 minutes after the drug was injected, there was a maximal decrease in blood pressure, then its gradual rise and stabilization at a lower level than the baseline one within the following 8 hours. There were no significant differences in the magnitude of a blood pressure reduction after administration of 1.5 and 3 mg/kg. CONCLUSION: The findings suggest that the dinitrosyl iron complex is highly effective in treating uncomplicated HC. The antihypertensive effect of the drug persists for 8 hours after its injection, which is very important during prehospital therapy. The drug is well tolerated by patients and causes an insignificant number of side effects.

[The study of hypotensive action of dinitrosyl-iron complex with glutathione containing drug oxacom in healthy volunteers].

On the basis of earlier executed studies of hypotensive effect of dinitrosyl iron complexes (DNIC) with glutathione, the drug has been created in industrial conditions named oxacom. Preliminary pharmacological studies of oxacom have not revealed negative qualities. The drug has been now tested in 14 healthy men in whom at single intravenous introduction it caused typical response - a decrease of diastolic as well as systolic arterial pressure on 24-27 mmHg through 3-4 min with subsequent very slow restoration in 8-10 hours. The heart rate after initial rise was quickly normalized. Echocardiography revealed unaltered cardiac output in spite of reduced cardiac filling by 28%. The multilateral analysis of clinical and biochemical data has revealed an absence of essential alterations which could lead to pathological consequences. The drug is recommended for carrying out of the second phase of clinical trial. The comparative study of the efficiency of hypotensive action of oxacom, S-nitrosoglutathione (GS-NO) and sodium nitrite (NO2) in rats has shown that the duration of effect was the greatest at oxacom action.

[Platelet activation and inflammation markers in patients with coronary heart disease and depression].

AIM: To study morphological features and functional activity of platelets, their relations with the level of inflammation markers in coronary heart disease (CHD) patients with depression. MATERIAL AND METHODS: The study group consisted of 33 CHD patients with stable effort angina (NY-HA FC I-III), 14 had depression, 19 were free of depression. Sixteen healthy volunteers comprised the control group. Platelet aggregation was registered by a mean size of aggregates and turbidometrically. Platelets shape, leukocytic-thrombocytic and erythrocytic-thrombocytic aggregates (LTA, ETA) in the whole blood were studied electron-microscopically. The levels of IL-2, IL-6, TNF-alpha, sVCAM, hsCRP were measured in the blood, serotonin--in platelets. RESULTS: Spontaneous aggregation enhanced in 52.6% CHD patients (p < 0.05). The blood contained reticular platelets, high number of prothrombocytes (p < 0.05), mean volume of thrombocytes was greater (p < 0.05). This reflected changes in megakaryocytopoiesis. Some of the patients had LTA and ETA. Out of inflammation markers, only IL-6 and sVCAM were elevated (p < 0.01), hsCRP concentration rose, but not above normal range. Serotonin in platelets was the same in the patients and controls. Depression aggravated the disorders and elevated other indices. Spontaneous aggregation was high in 71.4% of depressive CHD patients. The count of reticular platelets, prothrombocytes, mean volume platelets were also elevated. LTA and ETA were high in all the depressive patients. Elevated were also concentrations of IL-6, sVCAM, IL-2, hsCRP. Serotonin in platelets was low (p < 0.05). CONCLUSION: Depression stimulates functional activity of platelets, is a factor of risk of intravascular inflammation and contributes to development of thrombotic complications in CHD patients.

The University of Rochester model of breast cancer detection and survival.

This paper presents a biologically motivated model of breast cancer development and detection allowing for arbitrary screening schedules and the effects of clinical covariates recorded at the time of diagnosis on posttreatment survival. Biologically meaningful parameters of the model are estimated by the method of maximum likelihood from the data on age and tumor size at detection that resulted from two randomized trials known as the Canadian National Breast Screening Studies. When properly calibrated, the model provides a good description of the U.S. national trends in breast cancer incidence and mortality. The model was validated by predicting some quantitative characteristics obtained from the Surveillance, Epidemiology, and End Results data. In particular, the model provides an excellent prediction of the size-specific age-adjusted incidence of invasive breast cancer as a function of calendar time for 1975-1999. Predictive properties of the model are also illustrated with an application to the dynamics of age-specific incidence and stage-specific age-adjusted incidence over 1975-1999.

[Parametric survival analysis in patients with cervical cancer following fractionated radiotherapy: a new procedures and results]. / Parametricheskii analiz vyzhivaemosti bol'nykh rakom sheiki matki posle fraktsionirovannoi radioterapii. Novyi metod i rezul'taty ego primeneniia.

A recent theoretical result of Kendal (1998) enabled us to develop a survival model which allows for proliferation of tumor clonogenic cells in the course of fractionated radiotherapy. We explored this model during an analysis of clinical data on survival of 982 patients with cancer of the cervix uteri. The model provided a good description of survival patterns in different groups of patients. The estimated cure probability did not correlate with the rates of cell proliferation between exposures to radiation. Also, our results showed that this parameter cannot be estimated from survival data. Some light has been thrown on the relationship of cell proliferations taking place between exposures, on the one hand, and end-results of treatment for cancer of the cervix uteri, on the other.

[Defects in autonomic regulation in myocardial ischemia]. / Narusheniia vegetativnoi reguliatsii pri ishemii miokarda.

AIM: To evaluate cerebral and peripheral mechanisms of autonomic regulation of the cardiovascular system, their role in development of myocardial ischemia in coronary heart disease (CHD) patients with coronary atherosclerosis and X syndrome. MATERIALS AND METHODS: Psychometric testing, questionnaires, cardiovascular tests (by D. Y. Ewing), automatic spectral analysis of cardiac rhythm variability were used in investigation of psychovegetative regulation in 36 patients and 19 healthy subjects. Group 1 consisted of 26 CHD patients with coronary atherosclerosis and stable angina class I-II. Group 2 consisted of 10 patients with symptoms of myocardial ischemia and coronarographically intact coronary arteries. RESULTS: Patients of both groups demonstrated initial activation of cerebral sympathicoadrenal mechanisms manifesting with high anxiety, depression, vegetative defects in regulation of both initial autonomic tone and autonomic support of the orthostatic test. CHD patients with coronary atherosclerosis were characterized by persistent activation of cerebral sympathicoadrenal mechanisms and resistance of homeostatic baroreflex sympathetic systems. Vagal insufficiency was moderate and arose only at rest. In X syndrome patients with the same initial cerebral activation of the sympathicoadrenal mechanisms had dystonic trend in hemodynamic autonomic parameters: higher systolic blood pressure in subnormal heart rate, lability of baroreflex and cerebral mechanisms under the orthostatic test. The above features of psychovegetative relations make such patients very close to those with psychovegetative syndrome. CONCLUSION: CHD patients with coronary atherosclerosis and patients with X syndrome differ by mechanisms of maladaptation of autonomic regulation.

[Research on the factors determining cellular clonogenic capacity following fractional irradiation by the method of computer simulation modelling]. / Issledovanie faktorov, opredeliaiushchikh klonogennuiu sposobnost' kletok posle fraktsionirovannogo oblucheniia, metodami imitatsionnogo modelirovaniia na EVM.

Methods of multifactor dispersion analysis of variance of the results of imitation model tests were used to estimate the factors that influence the clonogenic capacity of cells after fractionated irradiation. The "interval between fractions" and "the share of cells at G0" were the major factors at different ratios between radioresistance and efficiency of repair of resting and proliferating cells.

[Correction of hemodynamics after peritoneoatrial shunt in liver cirrhosis with resistant ascites]. / Korrektsiia gemodinamiki posle peritoneoatrial'nogo shuntirovaniia pri tsirroze pecheni s rezistentnym astsitom.

Complex examination of hemodynamics was performed in 26 patients with cirrhosis of the liver with portal hypertension after operation of peritoneoatrial shunt using the methods of integral rheography, probing of heart cavities and pulmonary artery. Clinical results of the operations were analyzed. A conclusion was made of the absence of substantial alterations of gas exchange and hemodynamics of the lesser circulation. The alteration of the colloido-oncotic properties of blood are thought to be the leading factor in pathogenesis of the appearance of postoperative cardiopulmonary complications.

[Simulation modelling of cell systems in definitive and developing tissues]. / Imitatsionnoe modelirovanie kletochnykh sistem definitivnykh i razvivaiushchikhsia tkanei.

A review of simulation models of cells is provided, with a description of the basic methods of simulation. The deterministic and stochastic models of cell kinetics are considered on a few examples. A tendency has been revealed to applying the method computer reflection of the structure of heterogeneous cell systems. The utilization of specialized programmed languages of simulation is considered as promising.

[Study of factors determining the clonogenic capacity of irradiated cells by computer simulation]. / Issledovanie faktorov, opredeliaiushchikh klonogennuiu sposobnost' obluchennykh kletok, metodami imitatsionnogo modelirovaniia na EVM.

The methods of the multifactor disperse analysis of the results of studies of the simulation model of the effect of ionizing radiation on cell populations were used to study the role of some characteristics of the stationary culture in its response to a single radiation effect. The clonogenic capacity of cells was used as a criterion for assessing the biological effect of radiation. "The share of resting cells" was a predominant factor influencing the survival of irradiated cell populations.

[Modeling of the reliability of regenerating cell systems]. / O modelirovanii nadezhnosti obnovliaiushchikhsia kletochnykh sistem.

The paper deals with the mathematical model of reliability of simple renewal cell system consisting of two independently functioning populations of actively proliferating and differentiating (maturing) cells. The investigation of some properties of this model makes it possible to suppose that the mechanisms of tissue homeostasis may also participate in the maintenance of reliability of the relationship between cell proliferation and cell differentiation processes.

[Analysis of the kinetics of the transition of cells to DNA synthesis in systems with stimulated proliferation. II. Theoretical bases of the method]. / Analiz kinetiki perekhoda kletok k sintezu DNK v sistemakh so stimulirovannoi proliferatsiei. II. Teoreticheskie osnovy metoda

New kinetic criteria for analysis of the systems stimulated to proliferate were used for separate description of the initial and repeated entry of cells into the S period after the stimulation. An approach for estimation of temporal parameters of the S period of mitotic cycle is presented.

[Analysis of the kinetics of the transition of cells to DNA synthesis in systems with stimulated proliferation. III. Regenerating liver]. / Analiz kinetiki perekhoda kletok k sintezu DNK v sistemakh so stimulirovannoi proliferatsiei. III. Regeneriruiushchaia pechen'

The application of the previously reported methods of kinetic analysis to cell proliferation studies in the regenerating rat liver is under consideration. A fraction of hepatocytes (nearly 60% of the initial hepatocyte number) synchronously entering the mitotic cycle in response to partial hepatectomy has been discovered. The investigation of the temporal pattern of the kinetic criterium qS (t) allowed to make a detailed description of the main features of the transition of hepatocytes to DNA synthesis during the first 40 hours of liver regeneration. Using kinetic criteria of the initial and repeated entry of cells into S-period made it possible to reveal that the prereplicative period in the second mitotic cycle was shorter than that in the first one. Thus, the hypothesis about a special period which is necessary for the quiescent cell to acquire the competence to proliferation is additionally supported.

[Analysis of the kinetics of cell transition to DNA synthesis in systems with stimulated proliferation. I. Properties of a mathematical model of cell kinetics]. / Analiz kinetiki perekhoda kletok k sintezu DNK v sistemakh so stimulirovannoi proliferatsiei. I. Svoistva matematicheskoi modeli kletochnoi kinetiki

Some features of the mathematical model of cell kinetics in the systems stimulated or induced to proliferate are under consideration in this work. The proposed model serves as a basis of the kinetics analysis of the transition of cells to the DNA synthesis.