Cation influence on exciton localization in homologue scheelites.

Homologue scheelite crystals CaWO4, SrWO4, and BaWO4 possess similar crystal and electronic structure, but their luminescence exhibits drastically different thermal stabilities. By measuring the temperature dependence of the decay time of the intrinsic luminescence and fitting it to a three level model, we have qualitatively shown the effective exciton radius to increase in the order CaWO4 → SrWO4 → BaWO4, which explains the differences in the thermal stability. The origin of the variation in the exciton radii is suggested to be related to differences in the excited state dynamics in these crystals. From the decay kinetics measured under conditions of high excitation density, the efficiency of dipole-dipole interaction between excitons is shown to grow with exciton delocalization.

Role of cholesterol in the maintenance of endplate electrogenesis in rat diaphragm.

Methyl-ß-cyclodextrin (0.1 mM) reduced resting potential of muscle fibers and abolished local endplate membrane hyperpolarization in rat diaphragm. This effect was associated with selective reduction of electrogenic activity of α2-isoform of Na,K-ATPase without changes in the level of intracellular acetylcholine. Experiments with cholesterol marker filipin showed that methyl-ß-cyclodextrin in this dose induced cholesterol translocation from lipid rafts to liquid phase of the membrane without its release into extracellular space. This modification of lipid rafts by methyl-ß-cyclodextrin presumably impaired the mechanism maintaining electrogenesis in endplates mediated by modulation of Na,K-ATPase by non-quantum acetylcholine. Cholesterol can serve as a molecular component of this mechanism.

[GOOD PLANNING PRACTICE IN PRECLINICAL AND CLINICAL STUDIES OF UNFRACTIONATED AND FRACTIONATED HEPARINS IN RUSSIA AS THE BASIS OF SAFE AND EFFECTIVE ANTICOAGULATION THERAPY].

General principles of appropriate strategies for preclinical and clinical development of unfractionated and low-molecular-weight heparins and demonstration of their biosimilarity to corresponding reference medicinal products are provided. Demonstration of the biosimilarity of heparin-containing medicinal products constitutes the basis for their efficacy and safety during anticoagulation therapy. The main quality, safety, and efficacy characteristics of heparin products are described and the extent of non-clinical and clinical investigations necessary prior to drug marketing authorization are considered.

[Quality of life and cognitive functions in patients with end-stage renal failure on hemodialysis using a succinate-containing dialyzing solution].

AIM: To assess changes in quality of life (QL) and cognitive functions in patients with end-stage renal failure (ESRF) treated with hemodialysis using a succinate-containing dialyzing solution (SCDS). SUBJECTS AND METHODS: Sixty-seven patients with ESRF on hemodialysis using SCDS were examined. The investigators determined QL indicators using a Russianized variant of the Kidney Disease Quality of Life Short Form (KDQOL-SF) and the indicators of cognitive functions by the Benton visual retention test intended to evaluate visual short-term memory. The 6-minute walk test was used to evaluate exercise tolerance. The patients were examined before and 6 months after initiation of SCDS use. RESULTS: Following 6 months of SCDS treatment, the patients showed positive changes in a number of QL indicators. Their exercise capacity (p = 0.03) and the quality of sleep (p = 0.03), and social interaction (p = 0.02) were improved. The magnitude of the complaints related to disease and treatment decreased (p = 0.001). The level of patient frustration was reduced (p < 0.001). Different limitations associated with chronic kidney disease and dialysis therapy came to disturb the patients to a lesser degree (p = 0.02). The Bentoin visual retention test exhibited fewer errors (p = 0.04). CONCLUSION: Hemodialysis treatment with SCDS improved a number of QL indicators and cognitive functions in the patients.

[Our experience with tracheotomy in the hematological patients in need of prolonged artificial lung ventilation].

The objective of the present work was to study the possibility and technical peculiarities of planned tracheotomy in the hematological patients with thrombocytopenia and coagulopathy suffering severe concomitant pathology. A total of 45 tracheotomies were performed in hematological patients during the period from 2009 till July 2012. The case histories of 32 patients were available for the retrospective analysis. At the time of surgical intervention, 81% of the patients presented with grade IV thrombocytopenia. Five of the patients (15.6%) suffered bleeding from the tracheostomic canal in the early postoperative period. In four of them, hemorhage was stopped by the placement of the hemostatic sponge. One patient had to be managed by means of cauterization . Two (6.25%) patients developed inflammation around tracheotsoma. It is concluded that thrombocytopenia and probable coagulopathy do not constitute an absolute contraindication for planned tracheostomy. However, such operation may have a favourable outcome only after preliminary transfusion, the application of cauterization, and delicate surgical intervention.

[Clinical and laboratory evaluation of the efficiency of chronic hemodialysis treatment using acidosuccinate in patients with terminal renal failure].

AIM: To evaluate the efficiency of using a succinate-containing dialysis solution (SCDS) in terminal renal failure patients treated with chronic hemodialysis (CHD). SUBJECTS AND METHODS: Ninety patients from two hemodialysis units took part in the crossover study and were allocated to 2 groups. For 6 months, study group patients received CHD using SCDS and control group patients had CHD with a standard bicarbonate dialysis solution after 3-month washout period followed by decussation. The time course of changes in blood biochemical parameters, 24-hour ECG monitoring data, and quality of life indicators were estimated in the patients. RESULTS: After using acidosuccinate during hemodialysis, there was a significant reduction in the predialysis serum level of inorganic phosphate, a calcium phosphate product, gamma-glutamyl transpeptidase, urea, and aldosterone as compared to the control group. The blood concentration of total protein was also increased. After 6-month administration of acidosuccinate, the patients showed reductions in systolic blood pressure, heart rate, and the frequency and duration of ST-segment depression episodes. There were positive changes in the quality of life of patients according to the KDQOL-SF questionnaire. CONCLUSION: The use of SCDS in patients with CHD causes positive changes in a number of laboratory parameters and improves the physical and general status, and quality of life of patients.

[Demonstration of quality, safety and efficacy of biological products subject to changes in their manufacturing process].

Ensuring quality, safety and efficacy of the medicinal products placed on the market of the Russian Federation constitutes the area that requires strict regulation. When changes are made to the manufacturing process, the manufacturer generally needs to evaluate the relevant quality attributes of the product to demonstrate that modifications did not occur that would adversely impact the safety and efficacy of the drug. Where there is the lack of a sound legal basis, there is a need in harmonization of current Russian legislation with international and European rules governing medicinal product for human use to ensure quality, safety and efficacy thereof.

[The development of diagnostics of herpes viral infections].

The representatives of herpesviruses family (Herpesviridae--virus of herpes simplex and human cytomegalovirus) are largely widespread in human population. These herpesviruses bring on severe disorders of embryonic development up to fetal death, newborn diseases, neurologic disturbances, deafness, and blindness and in transplantation patients the severe internal organs affections and transplanted organs rejection. Both herpesviruses are able to affect the central nervous system and result in encephalitis with lethal outcome. The particular attention deserve the asymptomatic forms in case of which virus is excretee and can be transmitted both by horizontal line (sexual way included) and by vertical line (in the process of itrauterine development offtetus). The lacking of clear djfefrentiating clinical symtoms frequentyv observed under manifestations of herpesviruses infections brings another danger The comparison is made of fouur methods of detection of herpes simplex in urethra scrapes: the immunocytochemical method of detection of herpes simplex antigen in smears: the rapid cultural method; the immune-enzyme method of detection of herpes simplex antigen; the polymerase chain reaction. The results demonstrated that the rapid cultural method detected herpes simplex in infected samples on all stages of disease and in even more quantity at the stage of exacerbtion as compared with the polymerase chain reaction. The presented data testify the actuality of development of of laboratory diagnostics of herpesviruses injection to relevant diagnosis, determination of form and stage of disease, timely initiation of treatment and monitoring of therapy.

[Morphological and functional abnormalities in neuromuscular junctions of Drosophila melanogaster induced by the expression of human APP gene].

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the loss of neurocortical and hippocampal synapses that precedes amyloidosis and neurodegeneration and closely correlates with memory impairment. Mutations in the amyloid precursor protein (APP) cause familial AD and result in the increased production of amyloid-beta-protein (Abeta). To gain insights into synaptic effects of APP, we expressed APP, mutant form APP-Swedish and BACE in the motor neurons of fly larvae. We have shown that targeted expression of APP (APP-Swedish) in Drosophila larval motor neurons causes significant morphological and functional changes in neuromuscular junctions (NMJs): a dramatic increase in the number of synaptic buttons and changes in exocytosis as revealed by incorporation of the styryl dye FM4-64. Analysis of the number and distribution of mitochondria showed that motor neurons overexpressing APP (APP-Swedish) had a significant reduction of functional mitochondria in the presynaptic terminal. Significant synaptic abnormalities were observed for APP (APP-Swedish) and human beta-secretase (BACE) resulting in secretion of amyloid beta protein (Abeta). We suggest that APP participates in regulation of synaptic functions and its elevated expression leads to synaptic pathology independently from neurotoxic effects of Abeta.

[Good preclinical study, as an obligatory stage in design and clinical use of new medicinal preparations].

Preclinical studies are investigations, performed in vitro and in vivo (on animals) prior to clinical trials in men. They play the main role in design of medicinal preparations. Preclinical studies provide research of new compounds with useful biopharmaceutical and pharmacokinetic properties. In addition, they to make shorter the period between isolation of a novel active substance and its further development within the clinical trials, as well as to lower the time and materials expenditures for the clinical trials. There are three aspects of the preclinical study: investigation of the pharmacological activity of the main substance, investigation of the pharmacokinetic properties of the active substance and its medicinal preparation and investigation of the toxicological properties of the active substance. The requirements for preclinical studies on medicinal preparations and practical examples are presented.

Electronic structure and luminescence mechanisms in ZnMoO4 crystals.

Calculations of the band structure, partial densities of states and optical spectra of permittivity, reflectivity and absorption of perfect ZnMoO(4) crystal were performed using the full-potential linear-augmented-plane-wave method. It is shown that the calculated reflectivity spectra reproduce the main features of corresponding experimental spectra in the fundamental absorption region. The bandgap value of ZnMoO(4) is estimated as E(g) = 4.3 eV. Peculiarities of luminescence excitation spectra corrected for near-surface losses and losses on reflectivity are discussed, taking into account the results of the calculations. It is found that the energy structure of the lower part of conduction band is manifested in the excitation spectra of the intrinsic luminescence. The excitation spectra in the region 4.3-8.0 eV are formed by band-to-band electronic transitions mainly within the molybdate groups MoO(4)(2-), whereas electronic states of Zn(2+) cations are not directly involved into the excitation processes. It is shown that the structure of the intrinsic luminescence excitation spectrum depends on the temperature and mechanisms of the structure modification are discussed.

[Antiviral activity of recombinant interferon-alpha-2b in combination with certain antioxidant].

In vitro activity of interferon-alpha-2b in combination with various antioxidants against the influenza virus and Herpes simplex was studied. The standard strains and a clinical strain of Herpes simplex isolated from a patient with resistance to acyclovir were used. The in vitro studie showed that antioxidants, such as alpho-tocoferol acetate (vitamin E), Unithiol and ascorbic acid had a significant antiinfluenzae and antiherpetic action on the influenza virus A/H5N1 and Herpes simplex variants. They protected up to 100% of the cell monolayer from the virus cytopathic effect. The taurin solutions had no antiviral activity irrespective of the infection dose. Combinations of interferon-alpha-2b with alpha-tocopherol acetate (vitamin E), Unithiol or ascorbic acid showed a significant synergistic effect: the antiviral activity of interferon increased several times. The antiinfluenza activity of interferon-a-2b in the presence of various concentrations of taurin did not change.

[Effects of chronic nicotine exposure on electrogenic activity of the Na+, K(+)-ATPase and contractility in the rat diaphragm muscle].

Rats were chronically treated with nicotine via subcutaneous injections up to a dose 6 mg/kg/day during 2-3 weeks. After this period, resting membrane potential and action potentials of muscle fibres as well as isometric twitch and tetanic (20 s(-1) and 50(-1)) contractions of isolated rat diaphragm were studied. To estimate electrogenic contribution of the alpha2 isoform of the Na+, K(+)-ATPase ouabain in concentration 1 microM was used. Chronic nicotine exposure induced depolarization of resting membrane potential of 2.2 +/- 0.6 mV (p < 0.01). In rats chronically exposed to nicotine, electrogenic contribution of the Na+, K(+)-ATPase alpha2 isoform was twofold lesser than in control animals (3.7 +/- 0.6 mV and 6.4 +/- 0.6 mV, respectively, p < 0.01). Chronic nicotine exposure did not affect force of twitch and tetanic contractions in response to direct or indirect stimulation. A decrease in the twitch contraction time as well as in the rise time of tetanic contractions was observed. Fatigue dynamics was unchanged. The results suggest that chronic nicotine exposure leads to decrease of the Na+, K(+)-ATPase alpha2 isoform electrogenic activity, and as a consequence to damage of the rat diaphragm muscle electogenesis.

[Antioxidant impact on specific antiviral activity of human recombinant interferon alpha-2b with respect to Herpes simplex in cell culture].

In vitro synergistic antiviral effect of interferon alpha-2b in combination with unithiol (an antioxidant) on diverse variants of Herpes simplex, including the clinical acyclovir-resistant isolates, was demonstrated. Unithiol showed immediate antiherpes activity in the cell culture. However, its activity was lower than that of ascorbic acid, another highly active antioxidant. It was also observed that the specific antiherpes activity of interferon alpha-2b in the presence of unithiol increased several times. The data could be useful in the clinical practice, since the drugs combinations or complex formulations provide higher efficacy of the herpetic infection therapy with the use of the same concentrations of the available agents.

[Trigger regime of the functioning of a synaptic channel].

It has been shown using the linear model describing the dynamics of biochemical reactions occurring in a synapse that, as periodic step-like impulses pass through a synaptic channel, it operates in the triggering regime. The transmission of an impulse through the channel is associated with the change of the stationary point of the corresponding dynamic system compared with the unexcited state of the synapse. As a result, the system periodically evolves between two stable stationary states.

[Aggregative ability of thrombocytes and their receptor apparatus at a distant period after different operations on the injured spleen].

The aggregative ability of thrombocytes and the composition of the carbohydrate component of the thrombocyte glycoprotein receptors were studied in 126 patients after operations on the injured spleen within the terms of more than one year. It was found that organ-sparing operations and autolientransplantation in the injured spleen did not influence the changes of the thrombocyte aggregative properties at a remote postoperative period. Splenectomy results in an increased aggregative ability of thrombocytes at the expense of increased number of glycoprotein receptors containing D-mannose, N-acetyl-D-glucosamines, D-galactose, N-acetyl-D-glucosamines, N- acetylneuraminic acid and D-galactose.

Efficiency of anaferon in complex therapy of genital herpes.

We studied clinical efficiency and IFN-inducing activity of anaferon in chronic recurrent genital herpes with high incidence of relapses. The use of anaferon in complex therapy reduced the duration of intoxication symptoms and local symptoms, shortened the duration of the relapse, activated expression of IFN-gamma mRNA, and improved IFN-gamma-producing capacity of blood leukocytes.

[Viferon efficacy in influenza in adult patients].

The therapeutic efficacy of Viferon (suppositories of human recombinant interferon alfa-2) was investigated in a double-blind controlled study with the use of Arbidol as a reference drug in the treatment of patients with influenza. Viferon and Arbidol lowered the signs of the fever, intoxication, catarrh and the disease as the whole.

[Viferon suppositoria in therapy of relapsing herpesvirus infection in women].

The therapeutic efficacy of Viferon, a recombinant human interferon alpha-2b (rectal suppositoria) was studied in the therapy of relapsing herpesvirus infection in women. The clinical efficacy of the drug was recorded in 90% of the patients. The analysis of the remote results of the treatment made it possible to conclude that the Viferon suppositoria had an antirelapsing activity.