[The formation of bio-films by opportunistic microorganisms isolated from patients with rheumatic diseases].

The study was carried out concerning capability of 194 strains of opportunistic microorganisms to form bio-films. It is established that bacteria ecizing organism of patients with rheumatic diseases have capacity to form microbial bio-films. The formation of bio-films is manifested with the same rate as in agents of inflammatory processes. At that, Escherichia coli, Staphylococcus haemolyticus and bacteria of genus Proteus isolated under rheumatic diseases have significantly higher capability to form biofilms that matters for development of comorbide infections.

[Strategy for the use of chondroprotectors in osteoarthrosis].

Symptomatic slow-acting drugs (chondroprotectors) as different dosage forms have widespread application in the treatment of osteoarthrosis (OA) at different locations. The literature review considers their possible effect on carbohydrate metabolism, which is particularly important due to the high prevalence of diabetes mellitus in patients with OA. Current clinical recommendations for the use of chondroprotectors in the therapy of OA are given.

[Relationship of subclinical atherosclerosis indicators to exercise tolerance in patients with coronary heart disease].

AIM: To study the spread of a number of indicators of subclinical atherosclerosis in patients with coronary heart disease (CHD) and the pattern of their relationship to their functional state and muscle mass. SUBJECTS AND METHODS: Twenty patients with chronic forms of CHD were examined. Vascular wall stiffness was judged from pulse wave velocity (PWV) along elastic-type vessels, by calculating the carotid-femoral index (CFI). Endothelial function was estimated by endothelium-dependent vasodilation (EDV) in a reactive hyperemia test. Ultrasound scanning of the common carotid artery was used to estimate intima-media thickness. All the patients underwent bicycle ergometry; their exercise tolerance (ET) was determined by the amount of consumed oxygen when the metabolic equivalent (MET) was calculated; the percentages of active cell mass (ACM%) and lean mass (LM%) of total body weight were determined; the levels of total cholesterol, high- and low-density lipoprotein cholesterol, and triglycerides were estimated. A control group comprised 20 matched persons without CHD. RESULTS: A prognostically unfavorable increase of >12 m/sec in CFI was revealed in 20% of the patients with CHD and in 10% of the controls; endothelial vasomotor dysfunction (EDV < 10%) in 65 and 50%; a more than 0.9-mm increase in 55 and 15%, respectively. A low ET was stated in the majority of patients with abnormal vascular stiffness and endothelial vasomotor dysfunction. The CHD patients with a low ET were found to have significant correlations of CFI with ACM% and LM%, EDV and ACM% and LM%, CFI and EDV. The control patients with a low ET also showed correlations of EDV and ACM% and LM%. There was a correlation of ACM% and LM% with MET in both groups. CONCLUSION: EDV and PWV reflect a more decrease in physical activity and dysadapted functional status than in the degree of subclinical atherosclerosis.

[Efficiency of use of autologous activated serum in coxarthrosis].

AIM: To evaluate the clinical efficiency of using autologous conditioned (activated) serum (ACS) versus hyaluronic acid (HA) in coxarthrosis (CA). SUBJECTS AND METHODS: Two groups of patients (n = 54) who were matched for age, sex, and disease duration and had a valid diagnosis of CA were examined. During 3 weeks, Groups 1 and 2 patients received intra-articular therapy with ACS or synocrome forte (Croma Pharma, Sotex), respectively, for 3 weeks. A 12-month follow-up evaluated the magnitude of pain, by using the visual analog scale (VAS, mm), the functional index WOMAC and general health, by applying the EQ-VAS scale. RESULTS: The only benefit of HA was found to be more functional improvement as detected by the WOMAC index (-21.8%; t = 2.56) at an early (1-month) follow-up. After 3 months, the patients in the ACS group were recorded to have the maximum VAS pain intensity reduction that was 76.5% greater than that (t = 4.31) in the HA group. The clearest advantages of ACS therapy were traced 6 months after treatment. CONCLUSION: The use of ACS may be a real alternative to that of HA derivatives in achieving good clinical outcomes in patients with CA. After ACS administration, there was a long-term preservation of achieved positive results.

[Effect of local therapy of autolgous platelet-enriched plasma on pain syndrome in patients with knee osteoarthritis].

The influence ofplatelet-enriched plasma (PEP) ofpain intensity was estimated using a visual-analogous scale and the Wormac questionnaire in patients with knee osteoarthrosis (KOA). Beneficial effect on all variables studied was documented within I month after the onset of therapy. It was totally absent after 3 months in severe KOA but was apparent in typical KOA. Positive dynamics throughout months 1 and 3 was observed only in patients with early manifestations of KOA. It persisted during all 12 months of the study.

[Colonic microbial biocenosis in rheumatoid arthritis].

The aim of the work was to study colonic microbial biocenosis and colonizing ability of opportunistic bacteria in 32 patients with rheumatoid arthritis (RA) and 30 healthy subjects. RA was diagnosed based on the American Rheumatism Association criteria (1987). Qualitative and quantitative composition of the microflora was detected by a bacteriological method. StatSoft Statistics 6.0 was used to treat the data obtained. RA was associated with significant modification of the intestinal flora, viz. decrease in lactobacteria and significant increase of enterococci, clostridia, colibacteria showing reduced enzymatic activity, and opportunistic species. Also, symbiotic relationships between microorganisms altered. The fraction of bifidobacteria, bacteroids, and lactopositive colibacteria reduced while the abundance of opportunistic enterobacteria and staphylococci was elevated. Opportunistic Enterobacteriaceae were present in urine and nasal mucosa which suggested their translocation from the intestines. It is concluded that changes in intestinal microflora and colonization by opportunistic bacteria enhance the risk of development of co-morbid conditions in patients with RA.

[Effect of buried bound water in protein-ligand association processes].

The role of water molecules on the protein-ligand interface during macromolecular association has been determined. The free energy of association of insulin has been calculated by the molecular mechanics method using the continuum Poisson-Boltzman models. The previously developed scheme of the decomposition of association free energy onto contributions from individual interactions has been used to calculate intermolecular interactions, the solvation free energy, and the entropies of the process of macromolecular association. An analysis of the calculated oscillation spectra indicated that the presence of water molecules on the protein-protein interface promotes an increase in the contribution of vibration entropy to the free energy of association due to the enhancement of the flexibility of the complex. It was shown that water molecules involved in the formation of protein-water-ligand hydrogen bond change the balance of forces in the system.

[The influence of ration with different content of fat the pain syndrome in osteoarthrosis with the knee joint].

Study the influence of ration different content of fat the pain syndrome in osteoarthrosis with the knee joint. We examined 112 women at the age 59 (54-63) with osteoarthrosis the knee joint. Elicit what plenty in ration of fat (more than 45% caloric intake) promote the aggravation pain syndrome in the knee joint in osteoarthrosis patients.

[Alflutop in local therapy of shoulder periarthritis].

AIM: To study efficacy of a compound biological preparation alflutop in local therapy of shoulder periarthritis (SP), to compare its efficacy with that of periarticular diprospan. MATERIAL AND METHODS: The trial included 54 patients with SP. Clinical SP forms consisted of subacromial and subdeltoid bursitis (SSB) (42.6%), tendinitis (57.4%). Acute disease was diagnosed in 35.2% patients, chronic one--in 64.8%. Alflutop and diprospan were injected periarticularly. The patients were divided into three groups. Patients of group 1 (n = 15) received alflutop monotherapy (2 ml, 5 injections). Group 2 (n = 24) received a single injection of diprospan (7 mg). Group 3 (n = 15) patients were given combined treatment: a single injection (7 mg) of diprospan followed by alflutop infiltrations (2 mg, 5 injections). The efficacy of the treatment was judged by some score clinical parameters, dynamometrical findings, SDQ score set, thermographic and ultrasonic signs of periarticular inflammation. RESULTS: A course of periarticular alflutop infiltrations in SP demonstrated the same efficacy as a single dose diprospan. However, in acute SP with bursitis diprospan produced a significantly better results while alflutop was better in chronic SP with tendinitis. Diprospan combination with alflutop produced the highest therapeutic effect irrespective of the disease course and clinical SP course. CONCLUSION: Local administration of alflutop in SP as monotherapy alternative to glucocorticosteroids or in combination with diprospan is effective. A differentiated approach allowing for a clinical form and course of SP raises therapeutic efficacy noticeably.

The study of hydrophobic hydration in supercritical water-methanol mixtures.

We investigated hydrophobic hydration and heat capacity (CV) of diluted aqueous solutions of methanol at supercritical region using molecular dynamics method. We performed simulations for several concentrations of methanol and densities of mixtures. Similar to that observed for ambient conditions, the 600 K solution containing 0.12 mole fraction of methanol at the density of 0.98 gm.cm-3 yields the highest CV. The intermolecular structure between water and methanol molecules at this concentration was also found to be enhanced. Hydrophobic hydration, relative to ambient conditions, is diminished slightly at the concentration of Cv maximum and diminishes drastically for the other concentrations.

The use of homeopathic preparation Vozraston in the therapy of patients with rheumatoid arthritis.

We studied clinical and psychosomatic characteristics in 34 patients with rheumatoid arthritis. Sixteen patients received Vozraston (without considering the individual sensitivity) in addition to standard therapy. No changes in clinical and psychoemotional parameters were revealed. Vozraston reduced pain syndrome and increased the tone of the sympathetic nervous system.

[Negative consequences of enterosorption in rheumatoid arthritis]. / Negativnye posledstviia énterosorbtsii pri revmatoidnom artrite.

Aggravation of the patients with rheumatoid arthritis after enterosorption was apparently related to an increase in the rate of lipid peroxidation and to decrease in the antioxidation activity, which was expressed as a decrease in cholesterol and tocopherol content and an increase in ferrum and cuprum concentration in blood plasma. After-effect of alterations in phospholipid composition in blood plasma, erythrocytes, neutrophils and thrombocytes are also considered.

[Megaloblastic pancytopenia in a female patient with rheumatoid arthritis given methotrexate and amidopyrine simultaneously]. / Megaloblasticheskaia pantsitopeniia u bol'noi revmatoidnym artritom pri odnovremennom primeneniem metotreksata i amidopirina.

The paper is concerned with the development of megaloblastic pancytopenia in a female patient with grave rheumatoid arthritis. The patient had been given methotrexate (15 mg per week) for a long time, supplemented by amidopyrine (1.0 to 1.5 g/day). The author holds that the development of the above-indicated complication is provoked by both drugs interference into folate metabolism. It is concluded that caution should be taken as to the combined use of methotrexate with non-narcotic analgesic drugs, nonsteroidal anti-inflammatory agents and sulfanilamides.

[Lipid peroxidation and anti-oxidative systems of an organism in experimental streptococcal myocarditis and rheumocarditis]. / Perekisnoe okislenie lipidov i antioksidantnye sistemy organizma pri éksperimental'nom streptokokkovom miokardite i revmokardite.

Lipid peroxidation rate and activity of glutathione and tocopherol antioxidant systems were studied in rats with experimental streptococcal myocarditis and in patients with rheumatic carditis. During the acute period of inflammation content of diene conjugates and activity of glutathione reductase were increased in myocardium and erythrocytes of rats simultaneously with a decrease in tocopherol concentration in blood plasma. In the patients with rheumatic carditis activation of lipid peroxidation and the glutathione reductase was found in erythrocytes as well as a decrease of the tocopherol content--in blood plasma. Interrelationship between alterations in these patterns and their functions in rheumatic carditis pathogenesis are discussed.

[Antioxidant systems of erythrocytes in rheumatism]. / Antioksidantnye sistemy éritrotsitov pri revmatizme.

Patients with inactive and active rheumatic fever were examined for the intensity of lipid peroxidation of red blood cell membranes, lipid antioxidant system of tocopherol, non-lipid system of glutathione and related total activity of the pentosophosphate pathway of carbohydrate metabolism in red blood cells. It was established that activation of rheumatic process is accompanied by a increase in the content of diene conjugates in lipids of red blood cell membranes, a reduction of the tocopherol content in blood plasma, activation of glutathione reductase and glucose-6-phosphate dehydrogenase with the lowering of the total activity of the pentose cycle in red blood cells. The characteristics under study depended to a lesser degree on circulation insufficiency. The interrelationship between the shifts revealed is discussed, the mechanism by which they develop is suggested.

[System design of computerized devices for artificial cleansing of blood]. / Sistemnoe postroenie kompíuterizirovannoi apparatury iskusstvennogo ochishcheniia krovi.

The clinical efficiency, safety and accessibility of a lot of artificial blood clearance procedures are provided by the versatility of equipment operational capacities, computerization, automatization, expendable blood-conducting elements, higher independence through the electrochemical regeneration of a dialyzing solution, a reduced range of the hardwares used and their simplified designing implementation. A clearance technique-invariant pattern of polyblock of technical equipment with a universal perfusion unit wherein perfusion is accompanied by centralized equipment control has been proposed and introduced into practice.

[State of the art and outlook for promoting Russian-made hemodialysis equipment with regeneration of dialyzing solution]. / Sovremennoe sostoianie i perspektivy razvitiia otechestvennoi gemodializnoi apparatury s regeneratsiei dializiruiushchego rastvora.

Radical improvements in the physiological features and self-sufficiency of hemodialysis equipment, an essential reduction of the volume of dialyzate contacting with patient's body and elimination of dependence of the equipment operation on the availability of a water-supply network can be ensured by applying a regime of circulation of a relatively small volume (3-5 l) of dialyzate through the regenerating device. The regeneration unit must eliminate the organic products of dialysis from the dialyzate and stabilize the ionic composition of the purified dialyzate according to the preset parameters. Modern methods and technical means for regenerating the used dialyzate are discussed; a regeneration unit, which ensures an electrochemical oxidation (in the used dialyzate) of nitrogen-containing organic metabolites with a subsequent sorption-type additional purification of electrochemically-processed dialyzate, is offered. The regeneration unit is made up of an electrolyser, a sorption-type additional-purification device and a gas utilizer; it eliminates organic metabolites, phosphorus, calcium and potassium from the used dialyzate and stabilizes the pH solution.

Atomistic models for free energy evaluation of drug binding to membrane proteins.

The binding of various molecules to integral membrane proteins with optimal affinity and specificity is central to normal function of cell. While membrane proteins represent about one third of the whole cell proteome, they are a majority of common drug targets. The quest for the development of computational models capable of accurate evaluation of binding affinities, decomposition of the binding into its principal components and thus mapping molecular mechanisms of binding remains one of the main goals of modern computational biophysics and related drug development. The primary scope of this review will be on the recent extension of computational methods for the study of drug binding to membrane proteins. Several examples of such applications will be provided ranging from secondary transporters to voltage gated channels. In this mini-review, we will provide a short summary on the breadth of different methods for binding affinity evaluation. These methods include molecular docking with docking scoring functions, molecular dynamics (MD) simulations combined with post-processing analysis using Molecular Mechanics/Poisson Boltzmann (Generalized Born) Surface Area (MM/PB(GB)SA), as well as direct evaluation of free energies from Free Energy Perturbation (FEP) with constraining schemes, and Potential of Mean Force (PMF) computations. We will compare advantages and shortcomings of popular techniques and provide discussion on the integrative strategies for drug development aimed at targeting membrane proteins.

Insights into the molecular mechanism of hERG1 channel activation and blockade by drugs.

Blockade of the human ether-a-go-go related gene 1 (hERG1) channel has been associated with an increased duration of ventricular repolarization, causing prolongation of the time interval between Q and T waves (long QT syndrome, or LQTS). LQTS may result in serious cardiovascular disorders such as tachyarrhythmia and sudden cardiac death. Diverse types of organic compounds bind to the wide intracellular cavity in the pore domain of hERG channels, leading to a full or partial blockade of ion current through the pore. The drug-induced blockade of the hERG-related component of the potassium current is thought to be a major reason for drug-induced arrhythmias in humans. Identification of specific interactions governing the high-affinity blockade of cardiac potassium (K-) channels is crucial both for the prevention of unintended ion channel block and for the design of ion channel modulators. A plethora of ligand- and receptor-based models of K-channels have been created to address these challenges. In this paper, we review the current state of knowledge regarding the structure-function relationship of hERG and discuss progress in the use of molecular modeling for developing both blockers and activators of hERG.