[Rengalin, a New Efficacious and Safe Antitussive Agent. Results of a Randomized, Comparative, Multicenter Clinical Trial in Patients with Acute Respiratory Tract Infections].

UNLABELLED: Rengalin is a release-active combination antitussive drug based on antibodies to bradykinin, to histamine and morphine. It acts at various mechanisms of cough reflex by modifying endogenous target molecules and their interaction with receptors. The drug's efficacy, as demonstrated previously in experimental and clinical studies, is mediated by specific release-activity obtained as a result of the production process. METHODS: Efficacy and safety assessment of rengalin in the treatment of cough induced by acute upper respiratory tract infections (URIs) in comparison with a complex codeine-containing drug (codelac) was performed as part of a multicenter, randomized clinical trial involving 143 patients. All the participants presented with dry/non-productive cough caused by URIs (pharyngitis, laryngitis, tracheitis, tracheobronchitis, bronchitis). The duration of cough varied between 12 hours and 7 days. Rengalin was administered in 73 patients receiving 2 tablets 3 times daily for initial three days, and half reduced doses--for the subsequent four days; codelac was administered in 70 patients who were given 1 tablet 3 times daily for the entire treatment period (7 days). Primary efficacy endpoints were time to cough resolution and reduction in the severity of the cough (scored using a Cough Severity Scale). One patient in Rengalin group and three patients in Codelac group were withdrawn from the study. The article presents treatment outcomes obtained for 139 participants who completed the study in accordance with the protocol (Per Protokol-analysis). The data analysis was based on a non-inferiority (or comparability) statistical design for efficacy endpoints. RESULTS: The antitussive effect of rengalin was significantly comparable (p < 0.025) with that of codelac; the time to complete resolution of cough (both daytime and nocturnal) was 7.2 ± 1.0 days (versus 7.0 ± 1.1 in the group of codelac). Rengalin's efficacy was evidenced by a sufficiently reduced cough severity in the initial few days after treatment onset. As a result of the entire 7-day treatment, the severity score was reduced by 3.1 ± 09 (versus 3.1 ± 1.0 in the group of codelac; p < 0.05), totaling 0.2 ± 0.5 point in both groups at the end of the administration period. The frequent non-productive/dry cough was fully resolved in 76% of patients. All the participants in Rengalin group achieved either convalescent outcomes or significant improvement; none of the patients developed secondary bacterial complications. Positive changes in the patients' state over the week were finally confirmed by evaluating the total quality of life scores, including physical and mental component scores (SF-36 questionnaire), and total sleep quality scores, which were comparative between patients treated with rengalin and codelac (p < 0.025). At the end of the administration period, the effect of rengalin was rated by the physician investigators as 'pronounced'. The Clinical Global Impression Scale-Efficacy Indices (CGI-EI) in the groups of rengalin and codelac were comparable, equating a score of 3.7 ± 0.5 (p < 0.025). The safety outcomes of rengalin treatment were assessed across all 143 randomized patients. The drug's high safety profile was confirmed by the absence of adverse events that could be reliably related to the study treatment, and by monitoring of laboratory variables. Rengalin demonstrated good tolerability and favorable compatibility with other medications for URIs with concomitant pathology. The patients showed 100% treatment compliance. CONCLUSIONS: Rengalin is a new efficacious and safe drug indicated for the treatment of URI-induced cough. The severity of daytime and nocturnal cough begins to decrease as soon as on the first day after rengalin administration, with severity reduction observed throughout the whole treatment period. At the completion of the 7-day administration, cough severity is reduced by almost 100% and its changes are comparable with the outcomes of treatment with codelac. By targeting various cough reflex mediators, rengalin enables achieving an antitussive effect in the early days after URI onset (in dry, irritative cough episodes), and a protussive effect at later points of treatment. Rengalin promotes resolution of URI-induced cough without development of secondary bacterial complications.

[The directions and experiences of integration of clinical laboratory diagnostic and branch medicine].

The article considers the actual issues of teaching laboratory medicine to students of medical faculty and to physicians getting trained in different programs of postgraduate education. The major models of interaction between clinical physicians and specialists of laboratory diagnostic are considered. The proposed model of teaching of laboratory medicine is developed in collaboration with clinical chairs and is based on the principle of "clinical laboratory council of physicians". The analysis of clinical cases of specific patients and clinical analytical critiques are in the basement of the given system. The algorithm of considering one of situation tasks used in teaching is presented as example.

[Clinical, laboratory, and functional characteristic of patients with bronchial asthma and chronic obstructive pulmonary disease with disturbances of oxalic acid metabolism].

We studied the role of oxalate release through the airways as a potential injurious factor in the development of inflammation, bronchial obstruction and cough syndrome (respiratory oxalosis). Detection of oxalates in bronhcoalveolar lavage fluid and daily urine is the most valuable method for diagnostics of oxalates. Systemic effects, such as cholelithiasis, urolithiasis, and spinal osteochondrosis are characteristic clinical signs of respiratory oxalosis, besides purely respiratory symptoms.

[The treatment of patients with broncho-pulmonary pathology and concomitant disturbances of oxalic acid metabolism].

This work was aimed at estimating the role of special therapy of patients with bronchial asthma, COPD and hyperoxaluria designed to restrict the delivery or eliminate excess of oxalates and producing well apparent beneficial effect confirmed by the disappearance or decrease of clinical and functional manifestations of obstruction, reduction of requirements for broncholytic and anti-inflammatory agents.

[Consideration of the psychosomatic status as one of the conditions for effective treatment and controlled asthma].

The lecture is dedicated to the idea of a role of psychosomatic disorders in the occurrence and development of asthma, on the diagnosis and treatment of the neuropsychic type of its course, and on possibilities for psychotherapeutic correction.

[Bronchial asthma and obesity: common mechanisms].

The prevalence of bronchial asthma and obesity has grown in the recent decades. The mechanisms of these pathologies remain unclear despite a number of publications on the relationship between the two diseases. Analysis of the association of BA with obesity should take into account that both diseases develop in young children undergoing effects of breast milk and specific nutrients, intestinal colonization pattern (neonatal and early childhood), body mass at birth and it growth rate, sedentary lifestyle, and adipokine level in early ontogenesis. The available data suggest that the phenotype of BA associated with obesity is characterized by a number of clear-cut peculiarities (more severe clinical manifestations with frequent exacerbaions and impaired control of the disease). Moreover; such patients show no signs of cellular inflammation. There are several distinct mechanisms characterizing obesity-associated BA, viz. co-morbid conditions such as gastroduodenal reflux disease, sleep apnea, obesity-associated systemic inflammation (elevated cytokine (IL-6, TNF-alpha) levels), oxidative stress, production of obesity hormones (leptin. adiponektin, resistin). Thus, BA and obesity have some common potential mechanisms, including genetic factors, systemic inflammation, mechanical factors, and concomitant diseases. Understanding the common mechanisms of these diseases will promote the development of new therapeutic strategies.

[Evaluating the activity of the apoptosis-regulating genes from Bcl-2, Bax expression, and caspase-3 activity in bronchial epithelial cells in patients with asthma].

The specific features of bronchial epithelial cell apoptosis in asthma were studied, by evaluating the activity of the apoptosis-regulating genes Bcl-2, Bax, and caspase-3. Fibrobronchoscopy with target biopsy of the bronchial mucosa was carried out in 21 asthmatic patients (the latter had given informed consent). The expression of Bcl-2, Bax, and CPP32 (caspase-3 activity) was determined in the bronchial epithelial cells by the immunohistochemical technique using the DAKO kits. Allergic asthma is characterized by higher Bcl-2 and lower Bax expression than non-allergic asthma and in patients receiving systemic glucocorticosteroids. The similar nature of changes was found in the analysis of the Bcl2/Bax ratio. Regardless of the type of asthma, the expression of caspase-3 was rather high. The specific features of impaired bronchial epithelial cell apoptosis in different types of asthma can determine the pathogenetic value of apoptotic disorders in the persistence of allergic inflammation.

[Effect of pneumo 23 vaccine administration in patients with chronic obstructive pulmonary disease of intermediate severity].

AIM: To study dynamics ofclinico-immunological parameters in patients with chronic obstructive pulmonary disease (COPD) of intermediate severity after administration of Pbeumo 23 vaccine. MATERIALS AND METHODS: Forty-five patients with COPD of intermediate severity comparable to sex, age, duration of smoking and COPD history were divided on two groups: main group (I)--20 patients vaccinated with Pneumo 23 vaccine, and control group (II)--25 patients, which received only standard treatment. Complete blood count, sputum cytology, expiratory function as well as immunological parameters (levels of CD4+, CD8+, CD20+, CD25+, and IFN-gamma) were studied at baseline as well as 21 days, 3 months, and 6 months after vaccination. RESULTS: Stable remission of the disease (during 6 months) was noted in all patients in group I and in 20% of patients in group II. In group I, levels of CD4+ and CD8+ lymphocytes did not change significantly, whereas number of activated T-lymphocytes (CD25+) significantly increased. There were substantial increase of IFN-gamma level and decrease of IgE level in serum in group I that could point to predominance of Thl-dependent immune response and activation of cellular immunity. There were no such changes in group II. CONCLUSION: Administration of Pneumo 23 resulted in decrease of intensity of local inflammation and prolonged remission of COPD that allowed to recommend inclusion of vaccination to standard protocols of treatment for such patients.

[Radiation sterilization of units of a Mars descent module--a miniature meteorological station].

Subject of the test was a procedure of electron sterilization of Mars descent module units. As a result, data on distribution of absorbed dose field across the surface and by the entire volume of the mockup of a miniature meteorological station (MMS) were obtained In addition, electron sterilization technology was developed and the range of absorbed dose from electron radiation that will sterilize reliably packaged MMS hardware were defined in the interval from 30 to 40 kGy.

[Disturbance of apoptosis of peripheral blood lymphocytes in different variants of bronchial asthma].

AIM: To reveal disturbances of peripheral blood lymphocytes apoptosis in different variants of bronchial asthma (BA). MATERIAL AND METHODS: Apoptosis was studied in 20 healthy subjects, 70 BA patients: 32 patients with allergic BA (ABA) and 26 patients with non-allergic (NABA), 12 patients with BA treated with oral glucocorticosteroids. The following parameters of apoptosis were assessed: cell readiness for apoptosis (expression of CD95/Fas/APO-1 receptors), an early reversible stage of apoptosis (expression of phosphatidylserine on outer leaflet of lymphocyte membrane) and a late stage of apoptosis (the key effector caspase 3 activity). RESULTS: ABA is characterized by increased peripheral blood lymphocytes resistance to apoptosis: a decrease in expression of CD95/Fas/APO-1 receptors and phosphatidylserine on lymphocyte surface and caspase 3 activity. NABA is characterized by peripheral blood lymphocyte apoptosis activation at all stages: high expression of CD95/Fas/APO-1 receptors, expression of phosphatidylserine and caspase 3 activity. BA patients on systemic glucocorticosteroids are characterized by maximal expression of CD95/Fas/APO-1 receptors and phosphatidylserine on lymphocyte surface and the highest caspase 3 activity. CONCLUSION: The findings allow more accurate definition of the features of peripheral blood lymphocytes apoptosis in different variants of bronchial asthma and characteristics of relations between disturbed apoptosis and inflammation. Disturbances of apoptosis may be of pathogenetic importance in persistence ofallergic inflammation.

[Efficacy of vaccine therapy with ribomunil in patients with chronic obstructive pulmonary disease].

AIM: To assess efficacy of vaccine therapy with ribomunil in prevention of exacerbations and prolongation of remission in patients with obstructive pulmonary disease (COPD). MATERIAL AND METHODS: Fifty three COPD patients were divided into two groups: 28 patients of the study group received ribomunil plus standard therapy; 25 controls received only standard treatment. The examination of the patients included blood count, sputum cytology, external respiration function test, immunological investigation (CD4+, CD8+, CD20+, CD25+ and CD95+; IL-4, IFN-gamma, complement). The examination was made before the treatment, 21 days, 3 and 6 months after its beginning. Ribomunil was given 3 tablets in the morning before meal for 4 days in a week for 3 weeks, 4 days each month for the following 5 months. RESULTS: As a result of ribomunil treatment lymphocyte subpopulation normalized, immune response shifted to Th-1 dependent immune response, external respiration flow indices improved, remission prolonged. CONCLUSION: Ribomunil is recommended for wide application in the practice of COPD treatment

[Radiation sterilization of concentrated salt solutions]. / Radiatsionnaia sterilizatsiia kontsentrirovannykh rastvorov solei.

Purpose of the investigation was to develop a technique of irradiation sterilization of batch syringes with concentrated salt solutions (CaCl2 solution and a mixed solution of MgSO4, NaHCO3 and K2SO4). The syringes are used for mineralization of water produced by orbital systems of electrochemical regeneration of air humidity condensate, and deionized or distilled water from other sources. The paper describes composition of resultant potable water and analyzes quality of irradiation sterilization and stability of concentrated salts inside the syringes irradiated on gamma-source RTs-100M.

[The body's adaptation and responsiveness and their impact on the outcome of exudative pleuritis]. / Adaptatsiia, reaktivnost' organizma i ikh vliianie na iskhod éksudativnogo plevrita.

The authors studied homeostasis in 182 patients, including 126 patients with exudative pleuritis of tuberculous etiology and 56 with parapneumonic pleuritis. They determined the adaptive reactions of the body by the leukograms and the types of its responsiveness, established their relationship with other homeostatic parameters. Impaired responsiveness in patients with exudative pleuritis substantially affected the efficiency of etiotropic treatment. At the end of the basic course of therapy, the rate of marked residual pleural changes was 84.6% in patients with tuberculous pleuritis (Subgroup 1). Activation pathogenetic therapy with methyluracil promoted a reduction in the number of patients with significant residual pleural changes (32.8% in Subgroup 2).

[Epifamine efficacy in aspirin bronchial asthma]. / Effektivnost' lecheniia épifaminom aspirinovoi bronkhial'noi astmy.

Nine patients with moderate and severe aspirin bronchial asthma (ABA) received epifamine (a course dose 400 mg) in addition to continuous antiasthmatic therapy. Matched 12 ABA patients received placebo. Epifamine was found to improve the patients' clinical condition, response of distal bronchi to berotek; to promote achievement of long remission and increased production of melatonin. Thus, epifamine is effective and can be used in pathogenetic strategic therapy of ABA.

[Role of biological defects in formation and development of bronchial asthma and potentialities of premorbid diagnosis]. / Rol' biologicheskikh defektov v formirovanii i razvitii bronkhial'noi atmy i vozmozhnosti premorbidnoi diagnostiki.

The paper considers bronchial asthma as a polygenic disease. It presents some data available in the literature on the role of genetic disorders in the development of atopic states and the authors' own findings of various biological defects detected in apparently healthy blood relatives of patients with bronchial asthma. It is concluded that premorbid diagnosis is of importance in high risk persons.

[The study of biocide effectiveness of ultraviolet treatment in media stimulating space station environment]. / Izuchenie biotsidnoi éffektivnosti ul'trafioletovoi obrabotki sred, modeliruiushchikh ob''ekty kosmicheskikh stantsii.

An experiment was performed to study the biocide effect of ultraviolet treatment of simulated space station milieu. UV generated by low and moderately power-intensive sources (from 10 W to 1 kW) showed a good promise for decontaminating, within the reach, solid structural materials, and the air and water in the cabin. For instance, within 10 minutes of the UV-treatment aerial bacteria in 20 m3 were reduced in 12 to 30 times while fungal microflora was fully suppressed. Water containing spores and vegetative cells of both pathogenic and nonpathogenic microorganisms became essentially sterile after 4 to 10 minutes of treatment with low UV (in the order of 0.01 W/cm2). Different UV modalities can lay the basis for development of specific technologies of microbial decontamination of various spacecraft.

[Model study of ozone microbial decontamination effectiveness of space station environment]. / Model'noe izuchenie éffektivnosti ozonirovaniia dlia mikrobnoi dekontaminatsii sred v kosmicheskikh stantsiiakh.

Modeling experiments were performed to evaluate bactericide and fungicide effects of small ozone concentrations (0.3 mg/l of water and 47 mg/m3 of air) that can be generated onboard spacecraft following one hour after treatment. Over the period of treatment, reduction in aquatic microorganisms made up, depending on biotest in use, hundred and more times; concentration of atmospheric microorganisms showed a 5- to 10-fold reduction. The demonstrated effectiveness of ozone shows that it may advantage sterilization and cleaning from microorganisms a number of life support systems aboard manned space vehicles and stations.

Selection of sterilization methods for planetary return missions.

Two tasks must be accomplished to provide planetary protection for Mars return missions: (1) sterilization of the scientific module to be landed on Mars and (2) reliable sterilization of all material returned to Earth, while ensuring the scientific integrity of martian samples. This paper examines similarity and differences between these two tasks, and includes a discussion of technological implementation conditions and the nature of terrestrial and hypothesized martian microflora. The feasibility of a number of chemical and physical (ultraviolet and ionizing radiation and heating) methods of sterilization for use on the ground and onboard are discussed and compared. A combination of different methods will probably be selected as the most appropriate for ensuring planetary protection on the return mission.