[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 One patient in Rengalin group and three patients in Codelac group were withdrawn from the study.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 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.

[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 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.

[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

On the correlation of S-S and C-S raman bands frequencies and intensities with conformations of disulfide bridges in proteins.

We have studied dependence of the S-S and C-S raman bands frequencies and intensities on the conformation of disulfide bridges. These correlations have been analyzed on the basis of the normal coordinates treatment in the valence force field and from comparison of the raman and X-ray data for the model compounds and proteins. The found regularity of the intensity variations with conformation make it possible to distinguish these spectral perturbations from those associated with the change in the number of disulfide bridges in proteins. Particularly, this was demonstrated on the gamma-irradiated insulin solutions spectra. We also present some data appropriate for estimation of the content of disulfide bridges in proteins using internal intensity standards.

The experimental study of microbial contamination of the space hardware.

The role of potential contaminants of design materials and products of space technology--aerobic and anaerobic prokaryotes (myxobacteria, eubacteria, corinebacteria, actinomyces), and eukaryotes (micromyces), psychrophilic, mesophilic and thermophilic forms, chemolythotrophic microorganisms is discussed in this paper. The methods of analysis of microbial contamination in the solution of problem of the planetary protection are considered. The necessity of the use of ultrasound at the evaluation of surface and subsurface contamination of specimens is demonstrated; methods of determination of buried contamination (with the use of organic solvents and mechanical pulverization) are discussed. The data on buried and subsurface contamination for some materials and electronic parts together with microflora resistivity to sterilizing treatment are given.

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.

Radiation and thermal stabilities of adenine nucleotides.

We have investigated in detail radiation and thermal stabilities and transformations of adenosine mono- and triphosphates in liquid and frozen solid aqueous solutions within a wide range of absorbed radiation dose (up to 75 kGy) and temperature (up to 160 degrees C). Dephosphorylation is the main pathway of high temperature hydrolysis of adenine nucleotides. Basic thermodynamic and kinetic parameters of this process have been determined. Radiolysis of investigated compounds at room temperature results in scission of N-glycosidic bond with a radiation yield about of 1 mol/100 eV. Solution freezing significantly enhances radiation stability of nucleotides as well as other biomolecules. This circumstance is essential in the discussion of panspermia concepts.

Modern aspects of planetary protection and requirements to sterilization of space hardware.

The viewpoint of working group of Russian experts on the problem of planetary protection for future manned and unmanned Mars mission is presented. Recent data of Martian environment and on survival of terrestrial microorganisms in extreme conditions were used for detailed analysis and overview of planetary protection measures in regard to all possible flight situations including accidental landing. The special emphasis on "Mars-94" mission was done. This analysis resulted in revised formulation of spacecraft sterilization requirements and possible measures for their best implementation. New general combined approach to spacecraft sterilization was proposed. It includes penetrating radiation and heat treatment of spacecraft parts and components which is to be carried out before the final assembly of spacecraft and gaseous radiation sterilization of the whole spacecraft during the flight to Mars (or from Mars for return missions).

[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.

[Disorders of the mechanisms of hormonal regulation in patients with bronchial asthma]. / O nekotorykh narusheniiakh mekhanizmov gormonal'noi reguliatsii u bol'nykh bronkhial'noi astmoi.

A total of 31 patients with bronchial asthma were examined with the use of the brief dexamethasone test. Some patients with bronchial asthma seemed to have impaired glucocorticoid function of the adrenals. Based on the own investigations and the reported data it is concluded that patients with bronchial asthma may have different types of glucocorticoid deficiency, particularly at the expense of the impairment of the central mechanism of the regulation of glucocorticoid hormones. It has been demonstrated that the brief dexamethasone test can be used for studying the disorders of glucocorticoid function of the adrenals.

[The effect of glucocorticoids on mineral metabolism in bronchial asthma patients]. / Vliianie gliukokortikoidov na mineral'nyi obmen u bol'nykh bronkhial'noi astmoi.

Nuclear-absorption spectrophotometry (AAC-508, Hitachi, Japan) and selective ionometry (microlyte, Kone, Finland) were employed to measure magnesium and calcium concentrations in the serum, red cells, lymphocytes, 24-h urine and exhaled air moisture in 40 patients with hormone-dependent asthma (BA) and 15 BA patients given beclomet, becotid in inhalations and injections of hydrocortisone, prednisolone and dexason. Intravenous infusions and steroid inhalations in moderate doses for 10-14 days induce only insignificant changes in bivalent cation homeostasis. Complications associated with deranged mineral metabolism occurred more frequently in BA patients on long-term (at least 4 years) courses of oral glucocorticoids. Increased renal and bronchial excretion of magnesium and calcium in patients with hormone-dependent BA with complications of glucocorticoid therapy shows its significant contribution to development of steroid osteopathy and myopathy.

[Features of absorption of cortisol by peripheral blood cells in patients with bronchial asthma]. / Osobennosti pogloshcheniia kortizola kletami perifericheskoi krovi u bol'nykh bronkhial'nu astmoi.

Hydrocortisone absorption by lymphocytes and red blood cells was reduced in patients with bronchial asthma (BA). Adrenaline produced the stimulatory effect on hydrocortisone absorption by lymphocytes and red blood cells in practically normal subjects and in BA patients in whom that effect was decreased. In patients with the steroid-dependent clinico-pathogenetic pattern of BA, hydrocortisone absorption by lymphocytes was reduced to a considerable degree. It is stressed that cellular mechanisms of glucocorticoid insufficiency are implicated in the BA pathogenesis.