[Topical therapy of acute nociceptive pain: results of an open randomized clinical trial of the domestic drug Alental cream]. / Topicheskaya terapiya ostroi notsitseptivnoi boli: rezul'taty otkrytogo randomizirovannogo klinicheskogo issledovaniya otechestvennogo preparata Alental' krem.

OBJECTIVE: Evaluation of the therapeutic efficacy, safety and tolerability of the drug Alental cream for external use (VERTEX, LLS, Russia) compared with the original drug - Aertal cream for external use (Gedeon Richter, LLS, Hungary) for local therapy of acute nociceptive pain syndrome in patients who have suffered traumatic ankle injury. MATERIAL AND METHODS: The study included 131 patients who had suffered an injury to the soft tissues of the ankle joint. The 1st comparison group received the drug Alental cream, the 2nd group - Aertal cream. The duration of therapy was 7 days. The effectiveness of the drugs was evaluated during treatment based on the dynamics of the intensity of pain syndrome and other symptoms of trauma, as well as the assessment of these changes by the doctor and the patient. The safety analysis included the registration of adverse events according to clinical and laboratory studies. RESULTS: Alental cream in terms of therapeutic efficacy was equivalent to the registered original preparation Aertal cream. The analysis of the assessment of the dynamics of clinical and laboratory parameters, the safety of treatment, including the frequency of adverse events, did not reveal significant differences between the two drugs. CONCLUSIONS: Alental cream can be used as a means for local therapy of acute nociceptive pain syndrome in traumatic soft tissue injuries.

Morphological aspect of crystal nucleation in wall-confined supercooled metallic film.

In this paper, we simulate the nucleation and growth of crystalline nuclei in a molybdenum film cooled at different rates confined between two amorphous walls. We also compare the results for the wall-confined and wall-free systems. We apply the same methodology as in the work (Kirova and Pisarev 2019 J. Cryst. Growth 528 125266) which is based on reconstructing the probability density function for the largest crystalline nucleus in the system. The size of the nucleus and the asphericity parameter are considered as the reaction coordinates. We demonstrate that in both the free and confined systems there are two mechanisms of crystal growth: the attachment of atoms to the biggest crystal from the amorphous phase and the merging of the biggest crystal cluster with small ones (coalescence). We show that the attachment mechanism is dominant in the melt cooled down at a slower rate, and the mechanism gradually shifts to coalescence as cooling rate increases. We also observe the formation of long-lived crystal clusters and demonstrate that amorphous walls do not affect their geometric characteristics. However, system confined between walls demonstrates higher glass-forming ability.

Collective behaviour of a glass-forming film of pure aluminium.

The previously discovered features of the temperature behaviour of four-point spatial correlators allow us to study transitions to metastable states. Similar integral characteristics simultaneously study microscopic effects (vortex formation and clustering) and the effect of these phenomena on the thermodynamics of the whole system. It is shown that spatial and temporal behaviour of correlators in supercooled liquid samples determine the signs of the glass transition in a system before its relaxation. After the liquid sample is supercooled below a certain boundary, particle motion correlations on the coordination spheres sharply increase, similar to the situation in a crystal. The study was carried out using the embedded atom method model of aluminium using the molecular dynamics method.

[Results of an open, randomized, actively controlled study of the efficacy and safety of the new drug Freinozole nasal spray (Phenylephrine + Cetyrizine) in patients with acute respiratory infection]. / Rezul'taty otkrytogo randomizirovannogo aktivno-kontroliruemogo issledovaniia éffektivnosti i bezopasnosti novogo lekarstvennogo preparata Frinozol sprei nazal'nyi (Feniléfrin + Tsetirizin) u patsientov s ostroi respiratornoi infektsiei.

The aim of the study was proof of efficacy and safety of the drug Frinozol nasal spray in patients with acute respiratory infection (acute rhinitis). PATIENTS AND METHODS: A randomized open-label study with active control included 134 ambulatory patients: men and women aged 18 to 65 years with acute upper respiratory tract infection (acute rhinitis) lasting no more than 48 hours before inclusion into the study. Patients were randomized in two groups: group 1 took Frinozol nasal spray 2 sprays per each nostril three times a day for 7 days, subjects randomized to the group 2 took Vibrocil at the same dose and treatment regimen. The primary efficacy endpoint in the study was assessment of the dynamics of symptoms such as nasal congestion, rhinorrhea, itching in the nose and hyposmia using 10 cm VAS in 1 day after the start of treatment compared to the baseline. Secondary endpoints included assessment of the dynamics of nasal symptoms after 7 days of treatment, changes in the values of the Congestion Quantifier 5, CQ-5 questionnaire and evaluation of the effectiveness by the investigator. Safety analysis was carried out throughout the study and included the assessment of adverse events, laboratory data, vital signs, ECG assessment. RESULTS: According to the results of the study and comparative analysis of the primary (assessment of the dynamics of nasal symptoms on a 10 cm visual analogue scale 1 day after the start of treatment) and secondary efficacy endpoints as well as a comprehensive safety analysis, it can be concluded that the study drug is not inferior to the reference drug. Thus, the new combination Frinozol nasal spray is an effective and safe treatment for patients with acute respiratory infections.

Fluorescence Polarization Immunoassay, for Express Control of Antibiotic Levels: Design and Characteristics for Chloramphenicol, as an Example.

Characteristics of the fluorescence polarization immunoassay (FPIA) as a mean for express control of antibiotic levels in various specimens and its advantages vs. other analytical tests are described. The developmental stages of the analytical procedure and its parameters are considered for chlorampnenicol as an example. The analysis is based on competitive interaction of anti-chloramphenicol antibodies with the chloramphenicol-fluorophore conjugate and the potential free chloramphenicol in the specimen. The experimental results of the comparison of the chloramphenicol FPIA with the use of two conjugates differing in the length of the bridge length between the antibiotic functional groups and fluorophore (fluorescein) are presented. The requirements to the choice of the antibody and conjugate concentrations providing highly sensitive detection are characterized. The detection limit of chloramphenicol in the FPIA was 10 ng/ml and the determination of the concentrations ranged from 20 ng/mI to 10 mcg/ml. The time of the assay was 10 min.

Atomistic simulation of ion track formation in UO2.

The atomistic simulation of track formation due to the moving of swift heavy ion is performed for uranium dioxide. The two-temperature atomistic model with an explicit account of electron pressure and electron thermal conductivity is used. This two-temperature model describes a ionic subsystem by means of molecular dynamics while the electron subsystem is considered in the continuum approach. The various mechanisms of track formation are examined. It is shown that the mechanism of surface track formation differs from the mechanism of track formation in the bulk. The threshold values of the stopping power for track formation are estimated.

[Comparison of antibacterial activities of Tobramycin inhalation solutions].

Antibacterial spectra of Tobramycin-Gobby(solution for inhalation 60 mg/ml, "GobbyNovag C.A.", Argentina) and Toby (solution for inhalation 60 mg/ml, "Cardinal Health Inc.", USA) were estimated comparatively. The estimation involved 75 clinical isolates of microorganisms from the Culture Collection of the National Research Centre of Antibiotics and standard strains of Staphylococcus aureus ATCC 29213, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853.It was shown that Tobramycin-Gobby (solution for inhalation 60 mg/ml, "GobbyNovag C.A.", Argentina) and Toby (solution for inhalation 60 mg/ml, "Cardinal Health Inc.", USA) were identical by their antibacterial spectra.

[Omeprazol and ezomeprazol pharmacokinetics, duration of antisecretory effect, and reasons for their probable changes in duodenal ulcer].

There were authentic distinctions between the groups of healthy volunteers and patients with a peptic ulcer disease in Cmax, Tmax, AUC(0-t), AUC(0-infinity), CIt, Vd of omeprazole and Cmax of esomeprazole (Nexium, AstraZeneca). When the pharmacokinetics of omeprazole and ezomeprazole were compared in both groups, there were authentic distinctions in Cmax, AU(0-t), AUC(0-infinity), CIt, T1/2. The patients who had taken omeprazole the time of hypoacide condition was much shorter than in other groups. Disintegration test modeling pHmax for pH oscillation with large amplitude, that is typical for ulcer disease, demonstrated a possibility of early partial release of omeprazole, its acid-depended degradation and reduction of its bioavailability.

[Determination of cefixime blood plasma levels by HPLC].

For comparative study of the pharmacokinetics of Cemidexor (capsules of 100 mg) and Suprax (capsules of 400 mg), a method of HPLC with quantitative determination of cefixime (the active substance in the drugs) in the blood plasma of patients with UV detection was developed. The data teproducibility with an account of the admissibility criterion was observed within the interval of all the concentrations (0.06-10 mcg/ml). The accuracy and correctness of the method also corresponded to the admissibility criteria. The lower limit of the quantitative determimation of the cefexime blood plasma levels was 0.06 mcg/ml. The pharmacokinetics was studied with the open crossed randomized method. The results were used for calculation of the pharmacokinetic parameters required for estimation of the bioequivalence of the drugs. The statistical analysis of the pharmacokinetic parameters showed that Cemidoxor and Suprax were bioequivalent.

[Comparative estimation of pharmacokinetics of generic ribavirin-containing drugs].

Bioequivalence of the new Russian oral ribavirin-containing agents was estimated by the pharmacokinetic and bioavailability parameters vs. the original agent Rebetol. The agents were administered orally in single doses. The ribavirin blood levels were determined by HPLH. It was shown that the main pharmacokinetic parameters did not significantly differ. The agents proved to be bioequivalent.

[Comparative clinical and epidemiological evaluation of beta-lactam antibiotics in the treatment of intraabdominal infections]. / Sravnitel'naia kliniko-ékonomicheskaia otsenka betalaktamnykh antibiotikov pri lechenii intraabdominal'nykh infektsii.

We performed a retrospective, comparative study to evaluate efficacy, safety and economic outcomes of empiric cefoperazone/sulbactam monotherapy compared with the meropenem, imipenem/cilastatine and combination of cefepime plus metroindazol in patients with intra-abdominal infection. A total of 468 patients diagnosed with intra-abdominal abscess, peritonitis, pancreatitis were included in the study (the severity of infection according to scale APACHE II was less than 15). Patients were randomized to be treated with either 500 mg meropemen i.v. every 8 hours or 500 mg imipenem/cilastatine i.v. every 8 hours or 2 g cefepime i.v. every 12 hours plus 500 mg metronidazol twice daily or cefoperazone/sulbactam 2 g daily administered every 12 hours. Overall positive clinical responses (cure or improvement) were achieved at the end of treatment for 87.5 patients in meropenem group, 86.6% in the imipenem/cilastatin group, 85.3% in the cefepime group and 86.8% in cefoperazone/sulbactam group. Total cost of the treatment per 100 patients with intra-abdominal infections for cefoperazone/sulbactam was 1957031 roubles, for combinations of cefepime with metronidazol--2497815 roubles. For carbapenem group cost achieved for meropenem--3085291 rub., for imipenem/cilastatin--2653388 roubles. Rate "cost-effectiveness" in total: 784.47$ for cefepime, and 834.39$ for imipenem/cilastatine, 970.21$ for meropenem and 615.4$ for cefoperazone/sulbactam. The most expensive treatment was considered to be with meropenem and imipenem/cilastatine, main share is determined by initial cost of preparations. Less expensive was treatment by cefoperazone/sulbactam with cefepime and by metronidazol.

[Comparative study of azithromycin pharmacokinetics in healthy volunteers in open cross randomized procedure]. / Izuchenie sravnitel'noi farmakokinetiki preparatov azitromitsina u zdorovykh dobrovol'tsev otkrytym randomizirovannym perekrestnym metodom.

A method of quantitative determination of azithromycin in HPLC with mass spectrometric detection was developed. The detection limit is 0.5 ng/ml. The method was used in the study of pharmacokinetics and bioequivalence of Zi-Factor (capsules of 250 mg of azithromycin made by Veropharm, Russia) vs. reference-drug. The pharmacokinetic study was performed by the open cross randomized procedure in 18 volunteers. The pharmacokinetic parameters required for estimation of the drug bioequivalence were calculated. The statistical analysis of the pharmacokinetic parameters revealed bioequivalence of Zi-Factor and the reference-drug.

[Chemiluminescent immunoenzyme method for determining gidazepam]. / Khemiliuminestsentnyi immunofermentnyi metod opredeleniia gidazepama.

Competitive solid-phase enzyme immunoassay of gidasepam (a benzodiazepine) in the urine with chemiluminescent detection has been developed. The sensitivity of analysis for gidasepam is 10 ng/ml. Comparative measurements of benzodiazepines in the urine of patients abusing these agents by polarization fluorescence and the proposed method showed good coincidence of the results. The results demonstrate the possibility of using this method in medicine and narcology in combination with other instrumental methods.

[The effect of monoclonal and polyclonal antibodies to peroxidase on combined peroxidase oxidation of 4-iodophenol with luminol and 4-aminoantipyrine]. / Vliianie monoklonal'nykh i poliklonal'nykh antitel k peroksidaze na sopriazhennoe pereoksidaznoe okislenie 4-iodfenola s liuminolom i 4-aminoantipirinom.

The kinetics of peroxidase-dependent cooxidation for two substrate pairs [p-iodophenol + 4-aminoantipyrine (AAP) and p-iodophenol + luminol was studied both in the absence and presence of polyclonal antibodies (polyAB), three types of peroxidase-specific monoclonal antibodies (monoAB) and their double or triple mixtures in a wide range of H2O2 concentrations (0.01-10.0 mM). MonoAB 2C, 3E and 9D at concentrations of 0.05-500 nM inhibited the cooxidation of p-iodophenol + AAP at H2O2 concentration above 1.0 mM but activated the cooxidation of p-iodophenol + luminol. The double and triple mixtures of monoAB activated the cooxidation of p-iodophenol + AAP at the same H2O2 concentrations without any effect on the p-iodophenol + luminol cooxidation. PolyAB activated the cooxidation of p-iodophenol + AAP more effectively and only slightly activated (or inhibited) that of p-iodophenol + luminol. PolyAB diminished the values of rate constants for the interaction of the peroxidase active intermediates, E1 and E2, with p-iodophenol, AAP or luminol. Possible modes of monoAB and polyAB effects on the two substrate pair cooxidation are discussed.

A comparative study of peroxidases from horse radish and Arthromyces ramosus as labels in luminol-mediated chemiluminescent assays.

The properties of a peroxidase from Arthromyces ramosus (ARP) in the chemiluminescent reaction of luminol oxidation have been studied. These were compared with the properties of horse radish peroxidase (HRP) in the cooxidation of luminol and p-iodophenol, the enhanced chemiluminescence (ECL) reaction. By means of the stop-flow technique, ARP was shown to have an enzymatic activity toward luminol higher than that toward HRP. ARP can efficiently catalyze luminol oxidation in the absence of substrate enhancer. pH and substrate concentrations were optimized to determine ARP with the highest sensitivity. The detection limit of ARP was 5 x 10(-13) M, the same as that for HRP in the ECL reaction. The data on the use of ARP as a label in enzyme immunoassay of human IgG are presented. ARP was shown to have all the advantages of HRP as a label in chemiluminescent enzyme immunoassays: (i) high signal intensity, (ii) slow decay of luminescence, (iii) high signal/noise ratio, and (iv) as a consequence of (i)-(iii), high detection sensitivity. However, the low thermostability of ARP can limit the potential fields of its application.

[Study and immunoanalytical applications for peroxidase from Arthromyces ramosus]. / Issledovanie i immunoanaliticheskoe primenenie peroksidazy iz Arthromyces ramosus.

Some biochemical and catalytic properties of peroxidase from Arthromyces ramosus (EC 1.11.7.1) in chemiluminescent reaction of luminol oxidation by hydrogen peroxide were investigated. The second order rate constants were determined by the stopped-flow technique. Optimal conditions to quantity the enzyme were found, the detection limit being 5.10(-13) M. The peroxidase was used as a marker in the human IgG immunoassay.