[35th anniversary of the Chair of Orthopaedics and Traumatology of the Dnepropetrovsk Medical Institute].
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Biomedical subjects
Publications and source records attributed to L A Smirnova.
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Changes in the blood clotting system and rheology were studied in 39 patients during reconstructive operations making use of microsurgical methods. Effects of various doses of water soluble acelysine, an acetylsalicylic acid preparations (DL-lysine acetylsalicylate and glycine) have been evaluated during surgery and the immediate postoperative period. Clinical and laboratory changes in blood coagulation were determined at different doses (1000, 500, and 250 mg). Even in low doses (3.94 +/- 0.25 mg/kg) acelysine ensured chronometric and structural hypocoagulation as early as 1 h after dosed infusion and throughout the entire intervention, preventing thrombosis of microvascular anastomoses. Administration of acelysine in doses higher than 250 mg is not recommended, because higher doses involve the risk of hypocoagulation complications.
The mycelial pigment os Asp. niger VP has been fractionated into four fractions ehose solubility is similar to melanin pigments obtained from other sources. The addition of pyrocatechol, L-aspartic, benzoic, kojic and salicylic acids to the liquid Capek medium stimulates the fungal growth but diminishes the yield of fractions of the melanin pigment from the mycelium. Cinnamic acid does not influence the growth but also decreases the yield of the pigment. DL-tyrosine stimulates the fungal growth and produces no influence on the total yield of fractions 2, 3 and 4 from the mycelial pigment. All the cyclic compounds enhance the pigmentation of the culture liquid and give rise to the formation of fractions 2 and 3 of the melanin pigment. This latter constitutes a substantial portion of the dry matter of the fungal cell. The pigment content in the mycelium is much higher than that in the culture liquid of the corresponding culture.
HpaII/MspI blot-hybridization analysis of the 5'-end region of the calcitonin (CT) gene methylation in cells of bone marrow and peripheral blood of patients with acute lymphoblastic leukemias (ALL) has been carried out. ALLs are accompanied by hypermethylation of the inner cytosine in the CCGG sequences of this region of the CT gene. The level of hypermethylation of the CT gene corresponded to the degree of disease progression and malignancy. At a long-term remission, hypermethylation of the CT gene is not observed. In case of primary resistance or if the complete remission has not been achieved the CT gene remained hypermethylated. It has been shown that in relapse the normal CT gene methylation pattern reversed to hypermethylation. This phenomenon was detected 1-8 months before the obvious clinical and laboratory signs of the disease progression (relapse). The large size of abnormal HpaII-fragments of the 5'-end region of the calcitonin gene had a direct correlation with the malignancy status of ALL.
The kinetics of rithmidazole (an imidazobenzimiodazole derivative possessing the properties of I, III, and IV class antiarrhythmics) was studied upon a single intravenous introduction in rats (in a dose of 10 mg/kg) and in healthy male volunteers (300 mg/kg). The drug pharmacokinetics in rat blood plasma was characterized by rapid elimination from the systemic blood flow (drug detected by HPLC only within 6 h); the total plasma clearance was 1.43 liter/(h kg), the terminal half-elimination time was 1.76 h, and the equilibrium distribution volume (2.42 liter/kg) exceeded the total volume of water in the animal organism, which is indicative of a high level of absorption in tissues. The drug is characterized by a low level of binding to blood proteins and erythrocytes. Investigation of the drug distribution between tissues showed evidence of extensive, blood-flow-dependent penetration, with the drug concentration in most tissues exceeding that in the blood plasma. The maximum amounts of rithmidazole were found in the lungs, spleen, liver, and kidneys. The major excretion route for the unchanged drug is via urine and bile, amounting to 10% and approximately 1% of the dose introduced, respectively, determined within 72 h. The results are indicative of a low probability of the hepatoduodenal circulation of the unchanged substance: about 90% of the drug undergo metabolic transformation. The pharmacokinetics of rithmidazole in volunteers was also characterized by rapid elimination from the systemic blood flow; the total plasma clearance was 0.89 liter/(h kg), the terminal half-elimination time was 2.12 h, and the equilibrium distribution volume was 1.66 liter/kg. The obtained results show that the pharmacokinetic profiles of rithmidazole in rats and humans exhibit a similar character, with a high intensity of distribution and elimination processes.
Pharmacokinetic properties of benzimidazole derivatives drug possessing antipsychotic, actoprotector, antiarrhythmic, antiulcerogenic, antiallergic, uricosuric, anthelmintic activities have been summarized. Pharmacokinetics of benzimidazole derivatives used in veterinary practice as anthelmintic drugs is also considered. Benzimidazoles derivatives are characterised by multicompartment and ambiguous pharmacokinetic models. The derivatives of benzimidazoles are subjected to the first pass metabolism in the liver, and, therefore, they are converted to both active, and inactive metabolites. It is necessary to take into account for coadministration of benzimidazoles with other drugs. Hepatoduodenal circulation and repeated adsorption of unchanged drug and its metabolites in the gut is observed for benzimidazole. Many derivatives of benzimidazoles are characterised by rather low absolute bioavailability during peroral intake (from 2 up to 60%). Benzimidazsole derivative may bind to proteins and cell elements of blood. More often pharmacokinetic profile of benzimidazoles is linear for low doses, however, at high doses the linearity is lost. For animals and men pharmacokinetic models are always nearly identical.
Various methods of drug atomization and future prospects for their application in medical practice are considered. On the ground of a research into the influence produced by the administered doses and the density of the aerosol on the therapeutic activity the expediency of employing aerosol generators based upon pneumatic atomization by using the principle of ejecting an additional volume of air, as units yielding a substantial curative effect, is demonstrated. Data which bear proof to economic advantages of the units under review are given.
The introduction of principles of bloodless surgery into different areas of practical medicine is favoured by not only risks from donor blood transfusion, but also by the results of the researches dealing with the body's adaptation to acute anemia, with the determination of its allowable limits, and with much experience with bloodless operations used in Jehovah's Witnesses. The present study was undertaken to make a scientific-and-practical assessment of actual own blood funds and their introduction in order to decrease or refuse to use donor blood at cardiac surgery under extracorporeal circulation (EC). A retrospective analysis of hemotransfusion policy in 1993-2001 was conducted in over 2000 patients operated on under EC for coronary heart disease, acquired and congenital cardiac diseases at the Open Cardiac Surgery Department, Russian Surgery Research Center, Russian Academy of Medical Sciences. Own blood saving methods, such as intraoperative autohemotransfusion as two modalities, washed autoerythrocytic reinfusion, autoplasma reinfusion, as well as the use of different pharmaceuticals effective in reducing hemorrhage after EC were evaluated. The introduction of the above own blood saving methods may decrease the use of donor erythrocytes and freshly frozen plasma by 2.6 and 1.8 times, respectively, may completely refuse transfusing thromboplasma, assure adequate hemostasis, reduce the incidence of adverse reactions associated with donor blood transfusion in cardiac surgical patients. A complex use of the developed saving donor blood methods and pharmaceuticals aimed at improving hemostasis allowed donor blood transfusion to be completely refused in more than 70% of patients at aortocoronary bypass surgery under EC.
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Prostacyclin-thromboxane system and platelet hemostasis have been studied in 56 patients upon aortocoronary bypass surgery with uncomplicated early postoperative period. It has been established that cardiopulmonary bypass surgery leads to a considerable increase in 6-keto-PGF1 alpha and TXB2 levels per platelet, as compared to preoperative values. By hour 18 postoperatively 6-keto-PGF1 alpha to platelet number ratio returns to baseline, while TXB2 to platelet number ratio remains higher than preoperative values, which determines a shift in 6-keto-PGF1 alpha to TXB2 ratio towards TXB2, thus ensuring, probably, enhanced platelet aggregation properties. Thrombocytopenia, a decrease in platelet aggregation properties and elevated blood plasma level of beta-thromboglobulin were observed upon aortocoronary bypass surgery. By hour 18 postoperatively the number of platelets increased significantly, their aggregation properties were enhanced, beta-thromboglobulin blood plasma level was reduced, however, the parameters under study did not reach normal values at that time. Increased levels of 6-keto-PGF1 alpha and TXB2 per platelet in the early postoperative period are considered an important component of compensatory-adaptive body reactions directed to normalization of the damaged body functions, namely hemostasis and microcirculation.
Prostacyclin-thromboxane system (PTS) and platelet-vascular hemostasis have been studied in the preoperative period in 35 ischemic patients. A marked PTS disbalance with predominance of plasma thromboxane has been found. It has been established that in patients with postinfarction cardiosclerosis plasma prostacyclin content was significantly higher than in patients without myocardial infarction. The study of platelet function has demonstrated normal platelet aggregation rate and an increased level of beta-thromboglobulin in the blood of ischemic patients. Acetylsalicylic acid (250 mg/daily) was used for the correction of the disturbances observed, it reduced platelet aggregation, but had no effect on PTS and platelet release.
Female rats were treated with bemithyl (20 and 100 mg/kg) via a gastric tube during a 16-day period of lactation. It was found that the drug is transferred with breast milk to the organism of newborns, which leads to nonuniformities in their development. Among the early effects of bemithyl, most pronounced is the stimulating action upon maturation (muscle strength) and the development of sensor-locomotor reflexes; in the spectrum of long-term effects, the drug influence upon pubescence processes was manifested.
Blood heparinization was assessed, using two techniques (activated coagulation time--ACT and heparin concentration) in 31 patients during cardiopulmonary bypass surgery. It has been shown that ACT-technique, not always revealing heparin concentration, may serve as a criterion for blood heparinization adequacy during cardiopulmonary bypass, as in every case it reflects individual changes in anticoagulant blood activity.
The observations involved 1082 children ranging in ages from 11 to 14 years who had been annually given from one to four injections of inactivated chromatographic influenza vaccine. An additional group consisted of 242 children who after three years of vaccination with the inactivated vaccine were given a live influenza vaccine type A (H1N1) and A (H3N2) for children. The studies showed that the highest immunological effect in children was achieved after two years of vaccination with the inactivated influenza vaccine. No positive effect on the immune response in children was demonstrated by the addition of a live vaccine into the immunization schedule against the background of multiple immunizations with the inactivated one. Different types of responses in children to immunization against influenza were observed.
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