[Adequate assessment of linear function of calibration according to GOST R ISO 11095-2007 for ethanol mass concentration measurement]. / Otsenka adekvatnosti lineinoi funktsii kalibrovki po GOST R ISO 11095-2007 dlya izmereniya massovoi kontsentratsii etanola.

OBJECTIVE: To assess the adequacy of linear function of calibration according to GOST R ISO 11095-2007 for ethanol mass concentration measurement using internal reference materials (RMs). MATERIAL AND METHODS: An experiment on calibration in accordance with the GOST R ISO 11095-2007 National standard of the RF was carried out using internal RMs, namely aqueous solutions of ethanol at different concentrations. Measurements were performed for two subbands of ethanol concentrations at RMs: 0.15-1.05 and 1.0-7.0 mg/ml - according to the certified methodology. RESULTS: The graphs of the calibration's functions based on experimental data are consistent with the assumption of the calibration function's linearity, as well as the assumption of the standard deviation's constance of residues is equitable for two subbands of RMs. CONCLUSION: Proven linear models in the calibration experiment may be recommended for use in the ethanol mass concentration measurement.

Synthesis of a Bioactive Composition of Chitosan-Selenium Nanoparticles.

A biologically active composition of chitosan-selenium nanoparticles has been developed. Selenium nanoparticles are characterized by a clear bimodal size distribution: 2-3 and ~37 nm. The main active centers of complexation with nanoparticles are the amino and hydroxyl groups of chitosan. In experiments on culturing fibroblasts of the hTERT BJ-5ta cell line on sample films, high biocompatibility of the composition was shown. It was shown that the composition of chitosan-selenium nanoparticles has a corrective effect on the oxidative processes of the body, reducing the activity of free-radical oxidation in the blood of animals. This opens up prospects for the use of this complex in the composition of antioxidant and adaptogenic drugs.

[Pharmacokinetic and analgesic properties of the injectable dosage form of a new imidazobenzimidazole derivative RU-1205 with kappa agonist activity].

Pharmacokinetic properties of imidazobenzimidazole derivative compound RU-1205 were investigated after subcutaneous administration to rabbits as a substance and a dosage form (lyophilisates for injection) at a dose of 25 mg/kg. The lyophilisate was characterized by high values of the relative bioavailability. In tests, the "hot plate" and "vinegar cramps" the dosage form and the substance exhibited the same analgesic effect.

Pharmacokinetic Properties of a New Glutamic Acid Derivative Glutaron.

Inhomogenous distribution of glutaron in organs and tissues was found after intravenous and peroral administration: the agent demonstrated high affinity to organs with high degree of vascularization (lungs and heart) and elimination (kidney). Glutaron easily penetrates through the blood-brain barrier, which is consistent with its concentration in the adipose tissue.

[ABSOLUTE AND RELATIVE BIOAVAILABILITY OF GLUTARON--A NEW DERIVATIVE OF GLUTAMIC ACID].

The pharmacokinetics of studies of 3-phenylglutamic acid hydrochloride (glutaron) has been studied in rats. The main pharmacokinetic parameters show low values of the half-life (T1/2 = 3.75 h), mean retention time in the body (MRT = 5.77 h). The medium rate of drug concentration decrease in the blood plasma leads to a low value of the area under pharmacokinetic curve (AUC = 41.18 mg · h/mL). The general volume of distribution (Vd = 3.42 L/kg) is 3.5 times greater than the volume of extracellular fluid in the rat body. These data indicate a high ability of the glutaron to be distributed and accumulated in animal tissues. The value of absolute bioavailability is 84%, and the relative bioavailabity is 100%.

[Pharmacokinetic and analgesic properties of tabletized dosage form of RU-1205-new imidazobenzimidazole derivative with kappa agonist activity].

The pharmacokinetic properties of a new imidazobenzimidazole derivative, compound RU-1205, were studied after peroral administration to rabbits at a dose of 50 mg/kg as a parent substance and in coated tablet dosage form. It was found that RU-1205 tablets are characterized by high values of the relative bioavailability (105.3 +/- 11.7%). The results of hot-plate and vinegar-cramp tests showed that both the dosage form and parent substance produced the same analgesic effect. Granulated RU-1205 produced maximum analgesic effect (138.8% relative to control) within 4-h investigation and retained higher analgesic activity compared to that of parent substance (on the average by 58%, p < 0.05) up to 12 h.

GABA derivatives citrocard and salifen reduce the intensity of experimental gestosis.

Substitution of drinking water with 1.8 % NaCl solution in pregnant female rats from day 1 of gestation until parturitions was followed by the development of experimental gestosis. Gestosis manifested in an increase in BP by 18.2 %, protein concentration in the urine by 6.2 times, and edema severity in muscles, brain, and omentum in comparison with the initial level. The concentration of homocysteine in blood plasma of rats with complicated pregnancy 4.4-fold surpassed that in pregnant rats without gestosis, which can probably in a cause for gestosis development. GABA derivatives citrocard (50 mg/kg) and salifen (15 mg/kg), and the reference substance sulodexide (30 U/kg) reduced the severity of gestosis manifestations, which was seen from the absence of BP rise, decrease in urinary protein concentration by 1.9, 2.0, and 1.3 times and blood level of homocysteine by 1.7, 1.5, and 2.6 times, respectively, and a decrease in edema degree in comparison with female rats with experimental gestosis receiving physiological saline.

Adaptogenic effects of dihydroquercetin-chitosan composition during modeling of acute hypoxia.

The course of preventive oral treatment with a dihydroquercetin-chitosan composition produced a strong antihypoxic effect under conditions of experimental hypobaric hypoxia (arbitrary altitude 12,000 m). The lactate/pyruvate ratio in composition-receiving rats was much lower than in hypoxic animals (by 83%), but higher than in intact specimens (by 29%). The composition of chitosan and dihydroquercetin also possessed a strong antioxidant activity.

[The absolute bioavailability of benzimidazole derivative RU-1205 in rats].

Pharmacokinetics of morpholinoethylimidazobenzimidazole derivative RU-1205 with kappa-agonist activity have been studied. The pharmacokinetic parameters were determined upon intravenous (10 mg/kg), peroral, and subcutaneous (50 mg/kg) administration. It is established that RU-1205 substance has high bioavailability (44.17 and 56.03% upon peroral and subcutaneous introduction, respectively).

Study of the absolute bioavailability of citrocard, a new GABA derivative.

The main pharmacokinetic parameters attest to short elimination half-life and mean retention time of a single citrocard molecule. The average rate of plasma concentration decrease of the compound determined small area under the pharmacokinetic curve. Steady-state distribution volume was low and only slightly surpassed the volume of extracellular body fluids in rat, which indicated moderate capacity of citrocard to distribution and accumulation in the tissues, which is seen from low systemic clearance (Cl) despite the quick elimination of the compound. Absolute bioavailability was 64%.

[Hepatoduodenal circulation and excretion of the new GABA derivative citrocard].

Pharmacokinetic investigation of a new gamma-aminobutyric acid (GABA) derivative cirtocard showed that, upon the intravenous introduction, the drug is determined in high concentrations in organs of elimination--the liver and kidneys. The tissue accessibility amounts to 1.341 for the liver and 4.053 for the kidneys and the separation factor is 1.041 for the liver and 4.486 for the kidneys. The study of drug excretion showed that cirtocard is determined in the urine for 48 h, its nephritic clearance being 0.047 L/h and extra-nephritic clearance, 0.33 L/h. For the unchanged substance, a large significance ofhepatoduodenal circulation is low probable, since no more than 1 - 2% of the introduced dose was isolated with bile over entire experiment. It is established that the removal of the unchanged substance does not exceed 10% of the introduced dose. There is high probability of hepatoduodenal circulation and excretion of the preparation in the form of metabolites.

[Absolute bioavailability of the adenine derivative VMA-99-82 possessing antiviral activity].

Investigation of the main pharmacokinetic parameters of adenine derivative VMA-99-82 in rats showed large values of the half-life (T1/2 = 11.03 h) and the mean retention time of drug molecules in the organism (MRT = 9.53 h). A high rate of the drug concentration decrease in the plasma determines a small value of the area under the pharmacokinetic curve (AUC = 74.96 mg h/ml). The total distribution volume (V(d) = 10.61 l/kg) is 15.8 times greater than the volume of extracellular fluid in the body of rat, which is indicative of a high ability of VMA-99-82 to be distributed and accumulated in the organs and tissues. The absolute bioavailability of VMA-99-82 is 66%.

[Effect of new derivatives of natural nitrogen-containing compounds on the level and metabolism of biogenic amines in brain structures and the life span of rats].

Effects of the analogs of transmitter amino acids on the level of biogenic amines and their metabolism in various structures of brain and on the life span of rats have been studied.

[Neurochemical mechanisms of antidepressant action of new adenine derivative].

We have studied the influence of the new adenine derivative VMA-99-82 on the exchange of monoamines and their metabolites in the brain of Wistar rats. In addition, the effect of VMA-99-82 on binding of 5-HT1A and 5-HT2A serotonin receptors and the system of 3H-serotonin reuptake in the brain synaptosomes has been studied in vitro. It is established that VMA-99-82 at a dose of 10 mg/kg has no affinity to 5-HT1A and 5-HT2A serotonin receptors and produces no effect on the reuptake of [3H]-5-HT. It is suggested that VMA-99-82 has a modulating effect on ion channel NMDA receptor complex of the glutamatergic system, which leads to the manifestation of antidepressant activity.

[Treatment of patients with movement and cognitive disorders in the residual period of stroke].

The efficacy and safety of axamon was studied in a trial with parallel groups in patients, aged 65-88 years, with movement and cognitive disorders in the residual period of stroke. Twenty-five patients received basic therapy and 25 patients were treated with axamon as an add-on drug in dosage of 20 mg 3 times a day during 12 weeks. Along with the neurological examination, a battery of neuropsychological scales and tests was used. The reduction of cognitive and movement deficits was observed. Axamon promotes the optimization of restoration potential of patients in the residual period of stroke.

Analysis of antioxidant properties of chitosan and its oligomers.

Oral treatment with chitosan with a molecular weight approximately 105, but not its oligomer, reduced plasma content of free-radical oxidation products in normal rats and animals treated for the bone marrow form of radiation sickness and stimulated the recovery processes in involved bone marrow and peripheral blood.

[The effect of bemithyl on the onthogenesis of rats].

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.

[Pharmacokinetic properties of rithmidazole upon single intravenous introduction]. / Farmakokineticheskie svoistva ritmidazola pri odnokratnom vnutrivennom vvedenii.

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.

[Pharmacokinetics of benzimidazole derivatives]. / Farmakokinetika nekotorykh proizvodnykh benzimidazola.

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.

[Currently available blood saving methods in a patient at cardiac surgery under extracorporeal circulation]. / Sovremennye metody sokhraneniia krovi bol'nogo pri operatsiiakh na serdtse v usloviiakh iskusstvennogo krovoobrashcheniia.

Different blood saving methods are analyzed in 2000 cardiac surgical patients undergoing coronary and vascular bypass surgery in 1993 to 2000. The basic blood saving methods are as follows: intraoperative autoreinfusion (normovolemic thermodilution), reinfusion of the patient's blood, preoperative autologous plasma donation in combination with aprotinine, aminocapronic acid, etc. An analysis revealed a decrease in homologous blood components intraoperatively. Red blood cell transfusion decreased from 100% in 1993 to 44% in 2000, fresh frozen plasma and platelet transfusions did from 98 to 39% and from 96 to 1%, respectively. Intraoperative homologous blood transfusion could be avoided in 70% of those undergone coronary bypass surgery.