New Fluorescent Macrolide Derivatives for Studying Interactions of Antibiotics and Their Analogs with the Ribosomal Exit Tunnel.

Novel fluorescent derivatives of macrolide antibiotics related to tylosin bearing rhodamine, fluorescein, Alexa Fluor 488, BODIPY FL, and nitrobenzoxadiazole (NBD) residues were synthesized. The formation of complexes of these compounds with 70S E. coli ribosomes was studied by measuring the fluorescence polarization depending on the ribosome amount at constant concentration of the fluorescent substance. With the synthesized fluorescent tylosin derivatives, the dissociation constants for ribosome complexes with several known antibiotics and macrolide analogs previously obtained were determined. It was found that the fluorescent tylosin derivatives containing BODIPY FL and NBD groups could be used to screen the binding of novel antibiotics to bacterial ribosomes in the macrolide-binding site.

[Effect of hyperosmolar solutions on partial pressure of oxygen in arterial blood].

The study was undertaken to define the effect of hyperosmolar solutions on arterial blood oxygen levels. Analysis of arterial blood oxygenation after hyperosmolar solution infusions revealed a drop in partial pressure of oxygen (132.14 +/- 70.36, 120.0 +/- 66.48, and 119.24 +/- 70.10 mm Hg). At the same time there was a reduction in the extravascular lung water index (p < 0.05) as compared with the baseline values (7.93 +/- 2.17, 7.31 +/- 1.7), and Z62 +/- 1.99 ml/kg), respectively. This effect is particularly marked in a group of patients in whom the arterial blood content of oxygen is in the lower normal range. To evaluate and eliminate the above effect in reducing the arterial blood level, it is necessary to estimate respiratory indices during hyperosmolar solution infusion.

[Amino acid and peptide derivatives of the tylosin family of macrolide antibiotics modified at the aldehyde group].

Fourteen new functionally active amino acid and peptide derivatives of the antibiotics tylosin, desmycosin, and 5-O-mycaminosyltylonolide were synthesized in order to study the interaction of the growing polypeptide chain with the ribosomal tunnel. The conjugation of various amino acids and peptides with a macrolide aldehyde group was carried out by two methods: direct reductive amination with the isolation of the intermediate Schiff bases or through binding via oxime using the preliminarily obtained derivatives of 2-aminooxyacetic acid.

Ribosomal tunnel and translation regulation.

This review describes the results of recent studies of the ribosomal tunnel (RT), the major function of which is to allow the smooth passage of nascent polypeptides with different sequences from the peptidyl transferase center of the ribosome to the tunnel exit, where the folding of protein molecules begins. The features of structural organization of RT and their role in modulation and stabilization of the nascent chain conformation are discussed. Structural features of macrolide binding sites as well as application of macrolide antibiotics and their derivatives as tools to investigate ligand-tunnel wall interactions are also considered. Several examples of strong and specific interactions of regulatory polypeptides with nucleotide and amino acid residues of RT that lead to ribosome stalling and translational arrest are described in detail. The role of these events in regulation of expression of certain genes is discussed on the basis of recent high-resolution structural studies of nascent chains in the RT.

[The microcirculatory function and immune status indices of patients with rheumatic heart defects combined with pulmonary hypertension]. / Sostoianie mikrogemotsirkuliatsii i nekotorykh pokazatelei immunnogo statusa u bol'nykh revmaticheskimi porokami serdtsa v sochetanii s legochnoi gipertenziei.

Blood microcirculation and immunity were studied in 52 patients with rheumatic valve disease associated with pulmonary hypertension. The most pronounced changes were observed in patients with "active" pulmonary hypertension. Microcirculatory and immune disorders are likely to be pathogenetical factors aggravating prognosis of pulmonary hypertension.

[A comparative evaluation of the efficacy of quantum methods for treating hypertension patients]. / Porivnial'na otsinka efektyvnosti kvantovykh metodiv likuvannia khvorykh na hipertonichny khvorobu.

A study is presented of the effect of laser and microwave resonance therapy on the hemodynamics and hemorheology in 56 patients with hypertensive disease. The hypotensive effect of intravascular laser therapy is related to the positive changes, reduction of blood viscosity and general peripheral vascular resistance. The effect of low molecular electromagnetic radiation on acupuncture points favoured clear reduction of peripheral vessel resistance. Combination of laser and microwave resonance therapy produces a positive effect due to potentiation of these methods and, thus, influencing the systems of hemodynamics, hemostasis and hemorheology.

[The effect of the individual biorhythm on conjunctival microcirculation in hypertension patients]. / Vliianie individual'nogo bioritma na sostoianie kon''iunktival'noi mikrotsirkuliatsii u bol'nykh gipertonicheskoi bolezn'iu.

Deterioration of the condition in patients with arterial hypertension was found during the critical days of individual biorhythms and correlated with changes in the vascular and intravascular sector of the microcirculation. The peculiarities of individual biorhythms and state of microcirculation in patients with arterial hypertension allow to carry out timely and adequate drug correction of microcirculation disorders and central hemodynamics.

[The effect of the combined use of hemosorption and plasmapheresis on the blood rheological and hemodynamic indices of hypertension patients]. / Vliianie sochetannogo primeneniia gemosorbtsii i plazmafereza na gemoreologicheskie i gemodinamicheskie pokazateli u bol'nykh gipertonicheskoi bolezn'iu.

Basing on the response obtained in 46 patients with stage II essential hypertension, the conclusion is made on a positive action of hemosorption plus plasmapheresis on blood rheology, hemodynamics, clinical course of hypertension. The response persisted for up to 6 months.

[Hemodynamic changes in the greater and lesser circulations of patients with a mitral heart defect and primary pulmonary hypertension under the influence of differentiated treatment]. / Izmenenie gemodinamiki bol'shogo i malogo kruga krovoobrashcheniia u bol'nykh s mitral'nym porokom serdtsa i pervichnoi legochnoi gipertenziei pod vliianiem differentsirovannogo lecheniia.

The state of the greater and lesser hemodynamics in patients with rheumatic mitral heart disease complicated by pulmonary hypertension was analyzed after treatment with peripheral vasodilators and hemosorption. It is suggested that inclusion of hemosorption in the treatment complex favoured reduction of the degree of pulmonary hypertension, improvement of the central hemodynamics which may be directly related to improvement of the rheological properties of the blood.

[Plasmapheresis combined with hemosorption in the treatment of hypertension patients]. / Plazmaferez v sochetanii s gemosorbtsiei v lechenii bol'nykh gipertonicheskoi bolezn'iu.

It was established that use of plasmapheresis in association with hemosorption in 36 patients suffering of hypertensive disease improved the clinical course of the disease, reduced the resistance to drug treatment, increased the treatment efficacy, decreased the risk of complications. Simultaneously there was an improvement of the hemodynamics and hemorheological properties of the blood.

[New approaches to the treatment of primary pulmonary hypertension]. / Novye podkhody k lecheniiu pervichnoi legochnoi gipertonii.

A total of 43 patients with primary pulmonary hypertension were examined. The diagnosis was confirmed by invasive techniques and echocardiography. In addition to routine clinical studies, microcirculatory, central and pulmonary hemodynamic ones were used to examine the patients' status and to measure pulmonary pressure. Three groups of the patients were identified: (1) those who received UV-irradiated blood autotransfusion (n = 14); (2) those who underwent hemocarboperfusion with plasmapheresis (n = 15); (3) those who had their own drug therapy (n = 14). The immediate and long-term outcomes of the therapy were analysed. Indications were defined for the usage of extracorporeal techniques in the multimodality treatment of patients with primary pulmonary hypertension.

[Disorders of microcirculation and myocardial function in primary pulmonary hypertension and Eisenmenger's syndrome]. / Narusheniia mikrogemotsirkuliatsii i funktsional'nogo sostoianiia miokarda pri pervichnoi gipertonii i sindrome Eizenmengera.

Bulboangioscopy, aggregate state of the blood, ultrastructural examination of the microcirculatory bed of the skin, ultrasonic examination of the heart revealed that patients with primary pulmonary hypertension and Eisenmenger's syndrome did not show essential differences in the hemodynamics and blood microcirculation. In the treatment of these patients the stage of chronic circulatory insufficiency, vascular and intravascular disorders of the microcirculation should be considered.

Sorption therapy in psoriatic patients.

The results of psoriasis sorption therapy (hemosorption (HS), plasmosorption (PS), hemosorption with exchanged plasma transfusion) are presented in this work. Indices of immunity and clinical efficiency of sorption therapy in 89 examined patients are studied. It was determined that sorption therapy possessed therapeutic efficiency with clinical forms of dermatosis, it promotes the normalization of immunological status indices, blood aggregation condition and microcirculation.