Dynamics of Structural Parameters and Accumulation of Collagen Fibrils in Rat Lung after Inhalations of Surfactant-BL at Various Terms of Bleomycin-Induced Alveolitis.

Rats were subjected to surfactant-BL inhalations at the early and late phases of bleomycininduced alveolitis. In both regimens, the drug reduced the severity of inflammation. In the acute phase of alveolitis, the therapeutic effect of inhalation was accompanied by activation of the synthesis of fine lose collagen fibrils. In the late phase of alveolitis, inhalation of surfactant-BL thickened the fibrils and diminished their population in alveolar walls.

Effectiveness of correction of bleomycin-induced lung injury by early and late administration of surfactant-BL.

Rats were exposed to inhalation of surfactant-BL starting from the first or eighth day after intratracheal administration of bleomycin. At the early stages, the preparation effectively attenuated damage to ultrastructural components of the lung tissue and reduced the severity and extent of subsequent pulmonary pathology.

Therapeutic efficiency of early and late administration of surfactant-BL during bleomycin-induced damage to rat lungs.

Surfactant-BL was administered to rats via the inhalation route from day 1 or day 8 after intratracheal injection of bleomycin. Bronchoalveolar lavage and morphological characteristics of the lungs were compared. Administration of surfactant-BL at the early terms efficiently reduced the severity of bleomycin-induced alveolitis and atelectases.

[Specific features of the macrophage formula of bronchoalveolar lavage in patients with destructive pulmonary tuberculosis]. / Osobennosti makrofagal'noi formuly bronkhoal'veoliarnogo smyva u bol'nykh destruktivnym tuberkulezom legkikh.

The macrophageal elements (ME) of bronchoalveolar lavage were cytologically and electron microscopically studied in 11 patients with active pulmonary tuberculosis who took antituberculous drugs during 3-6 months, which did not yield a significant clinical effect (Group 1) and in 24 patients with the disease who received inhaled C-BL during chemotherapy (Group 2). The drug was administered in a dose of 20 mg by a nebulizer every second day during 4-9 weeks. In Group 1, the high levels of young biosynthesizing (32.08 +/- 0.10) and mature secreting (11.50 +/- 0.70) ME were combined with the lower counts of phagocytizing macrophages (11.50 +/- 0.90). In Group 2, the specific features depended on the duration of C-BL use and after 20-28 inhalations their composition tended to normalize: biosynthesizing (18.30 +/- 1.05), secreting (5.80 +/- 0.95), and phagocytizing (47.20 +/- 1.05). In 19 patients from Group 2, the therapeutic effect was clinically regarded as positive.

[Critical state medicine. Surfactant therapy of adult respiratory distress syndrome (results of multicenter studies)]. / Meditsina kriticheskikh sostoianii. Surfaktant-terapiia respiratornogo distress-sindroma vzroslykh (rezul'taty mnogotsentrovykh ispytanii).

The paper provides evidence for the pathogenetic approach to treating acute lung lesion (ALL) and adult respiratory distress syndrome (ARDS). An algorithm of the use of Russian lung surfactant preparations: CT-HL and CT-BL has been developed. In involves earlier (the first days following the onset of respiratory failure) use of surfactant, its combined bolus intratracheal or intrabronchial administration in doses of 200-400 mg/m2, followed by continuous (5-day) aerosol inhalation in doses of 20-30 mg/h for children and 30-75 mg/h for adults until pronounced clinical and X-ray effects are shown. Fifty three patients were found to develop ALL and ARDS in the presence of severe pneumonia, postperfusion lung disorders, reperfusion syndrome, pulmonary embolism, long-term artificial ventilation, combined car accident injury and gunshot wounds of the chest, heroine intoxication, septic shock, sepsis, postoperative sequels in cancer patients, and after hepatic transplantation or massive aspiration of gastric contents. Fifty patients were overcome their critical status, 44 survived. The duration of artificial ventilation (AV) ranged from 1 to 6 days. Earlier use of the drugs made it possible to transfer patients to safe AV regimens and to eliminate ALL and ARDS rapidly and to significantly reduce mortality due to critical states.

[Continuous inhalation administration of surfactant-BL for control of adult respiratory distress syndrome after reconstruction of the abdominal aorta]. / Dlitel'noe ingaliatsionnoe vvedenie surfaktanta-BL dlia kupirovaniia respiratornogo distress-sindroma vzroslykh razvivshegosia posle rekonstruktivnogo vmeshatel'stva na briushnoiaorte.

A 62-year-old patient with Leriche's syndrome and critical ischemia of the low extremities has undergone the surgery of aortofemoral grafting. A patient has developed the severe ARDS on the second day of reperfusion (bilateral diffuse infiltrates, PO2/FiO2 < 100, lung injury score was 3). Different ways of administration of bovine surfactant (SURFACTANT BL, Russia) were used during the treatment. Total application time was 84 hours, total dose was 4000 mg (50 mg/kg). Considerable improvement of lung function occurred after start of the continuous inhalation of surfactant with a constant rate of 63 mg/h. Two hours after this step PO2/FiO2 reached 400 mm Hg and remained stable 12 hours more, up to the end of surfactant administration. The patient was soon successfully extubated and discharged on the 25th day after surgery. It is supposed that in spite of a small total dose of bovine surfactant the success was achieved due to an early start of the surfactant replacement, continuous inhalation and its definite rate.

[Our experience in the use of a Russian preparation of pulmonary surfactant in the treatment of acute respiratory distress syndrome and severe pneumonia in children]. / Nash opyt primeneniia otechestvennogo preparata legochnogo surfaktanta dlia lecheniia sindroma ostrogo povrezhdeniia legkikh i tiazhelykh pnevmonii u detei.

Six critical patients aged 2 months to 13 years with lung diseases were treated by pulmonary surfactant preparation. Three of these children developed the acute respiratory distress syndrome in the presence of grave pneumonia (1 case), asphyxial drowing (1 case), and small-small intestinal invagination (1 case), three others developed acute bilateral large focal pneumonia with or without repeated atelectases. The drug Surfactant-BL was administered in a dose of 400 micrograms/m2 by instillations (2 cases) or by inhalation aerosols. The drug improved blood gases, lung compliance, x-ray picture, and clinical status of all patients, permitting a decrease in IMV/SIMV parameters within 12-48 h after the last administration and discontinuation of IMV/SIMV in 3 patients within 24 h after 1 or two administrations. Five children survived, 1 (with asphyxial drowning) died with brain edema and wedging syndrome. Surfactant-BL is a safe and effective drug; administration through alveolar nebulisers should be preferred.

[Radiation protective properties of a synthetic antagonist of glucocorticoids RU 38486]. / Issledovanie radiozashchitnogo deistviia sinteticheskogo antagonista gliukokortikoidov RU 38 486.

Radioprotective properties of synthetic antiglucocorticoid RU 38,486 were investigated. It was demonstrated that this antagonist of glucocorticoids possesses radioprotective effect in vitro and in vivo systems. Radioprotective properties at molecular level exhibited in inhibition of postirradiation endonuclease activation and in prevention of internucleosome chromatin degradation. Involvement of cytosol glucocorticoid receptors in initiation of radiation-induced programmed cell death is discussed.

Determination of some nuclear deoxyribonucleases in X-irradiated rat thymocytes.

The spectrum of nuclear nucleases in control and irradiated (4 Gy) thymocytes has been investigated. Using the method of SDS electrophoresis of nuclear proteins in 3H-DNA-polyacrylamide gels a number of polypeptides of MW. 35, 32, 17.7, 17.2 and 16.4 kDa possessing nuclease activity were found. The 35 kDa enzyme is only active in the presence of Ca2+ and Mg2+ ions. In response to cycloheximide injection (3 mg/100 g body weight) and irradiation, we did not detect the 35 kDa nuclease activity. Nucleases of 32, 17.7, 17.2 and 16.4 kDa are active in the presence of Ca2+ ions. The activities of these nucleases increases 60 min after irradiation. These nucleases were also found in the fraction of polydeoxyribonucleotide (PDN).

[The identification of Ca2+-dependent nucleases activated in the nuclei of rat thymocytes under the action of glucocorticoids]. / Identifikatsiia Ca2+-zavisimykh nukleaz, aktiviziruiushchikhsia v iadrakh timotsitov krys pod deistviem gliukokortikoidov.

Spectra of thymocyte's nuclear nucleases of control and glucocorticoid treated (5 mg/kg body weight) adrenalectomized rats have been investigated. Using the method of SDS-electrophoresis of nuclear proteins in 3H-DNA-polyacrylamide gel (PAAG) the authors managed to discover a number of polypeptides of 35, 32, 17.7, 17.0, 16.4 kDa molecular mass possessing a nuclease activity. The enzyme of 35 kDa is only active in the presence of Ca2+ and Mg2+ ions and inhibited by cycloheximide. Nucleases of 32, 17.7, 17.0, 16.4 kDa are active in the presence of Ca2+ ions. The enzymic activity of these nucleases increases 60 min after steroid treatment. Nuclease of 17.7, 17.0, 16.4 kDa are poly(ADP-ribosylated). Glucocorticoid mediated activation don't blocked by poly(ADP-ribosylation). Possible role and mechanism of discovered nucleases are discussed.

[The nuclear desoxyribonuclease (DNAse) spectrum of normal rat thymus cells and after whole-body x-ray irradiation]. / Izuchenie spektra iadernykh dezoksiribonukleaz (DNKaz) kletok timusa krys v norme i posle obshchego rentgenovskogo oblucheniia.

Spectra of thymocyte nuclear DNAases of control and irradiated (4 Gy) rats have been investigated. Using the method of SDS-electrophoresis of nuclear proteins in DNA-polyacrylamide gel (PAAG) the authors managed to discover a number of polypeptides of 35, 32, 17.7, 17.2, and 16.4 kDA molecular mass possessing a DNAase activity. The enzyme of 35 kDA is only active in the presence of Ca2+ and Mg2+ ions. Nucleases of 32, 17.7, 17.2, and 16.4 kDA are active in the presence of Ca2+ ions and inactive in the presence of Mg2+ ions or in the absence of divalent cations. A simultaneous addition of Ca2+ and Mg2+ ions to the incubation medium causes a synergistic effect with respect to the manifestation of these DNAase activities. Nucleases of 32, 17.7, 17.2, and 16.4 kDa only emerge after the preliminary removal of histones by ion exchange chromatography on a column with CM-sephadex C-50. The enzymic activity of 32 kDA protein increases 60 min after irradiation and drops to the control value in 4 h. At the same time, the postirradiation increase in DNAase activity of a low-molecular weight enzyme group remains invariable throughout the entire period of observation (1-4 h). The preinjection of cycloheximide (CHI) prevents the postirradiation degradation of chromatin and, simultaneously, makes the enzymic activity, corresponding to 35 kDA protein, disappear at the electrophoregrams. The experiments with CHI permit to identify the given enzymic fraction as Ca/Mg-dependent endonuclease. This indicates the participation of normally pre-existing Ca/Mg-dependent endonuclease in implementing the process of chromatin enzymic degradation in the irradiated thymocytes.

[Mechanism of thymocyte death in exposure to ultrahigh doses of gamma radiation]. / Issledovanie mekhanizma gibeli timotsitov pri vozdeistvii sverkhvysokikh doz gamma-izlucheniia.

A comparative study was made of the morphological and biochemical indices of rat thymus cells after gamma-irradiation with doses of 4-10 Gy (median), 20 Gy (high), and 200-400 Gy (superhigh). It was shown that 4 h after irradiation with superhigh doses the yield of polydeoxynucleotides (PDN) was twice as low as that observed after doses of 4-10 Gy. 24 h after irradiation the amount of the extracted PDN in thymocytes exposed to superhigh doses was markedly larger than that after 4 hours. After all doses applied chromatin degradation occurred at the internucleosome sites in a strict order, the activity of acid and alkaline nucleases being unchanged. A large number of cells have normal nuclear structure 4 h after irradiation (200-400 Gy), as was demonstrated by the electron microscopy data, while in 24 h no intact cells were virtually found in the thymus which correlated with the changes in the PDN yield. The mechanisms of the lymphoid cell death under the effect of different radiation doses are discussed.

Degree of chromatin fragmentation and frequency of nuclear pyknosis in Percoll-fractionated thymocytes of irradiated rats.

The relationship between nuclear chromatin degradation to polydeoxyribonucleotides (PDN) and other features of interphase death were studied using thymocytes of normal and X-irradiated rats. Fractionation of the thymic cells in Percoll gradients was performed in order to separate dead from intact cells. The degree of radiation-induced chromatin fragmentation, as assessed by electrophoresis, was similar for PDN from all Percoll bands. Following irradiation 87-98 per cent of 'heavy' thymocytes were pyknotic and almost devoid of receptors to autologous erythrocytes thus comprising a dead cell population. A direct relationship between PDN content and nuclear pyknosis was noted throughout the gradient. The loss of autologous rosette-forming ability was directly related to other indices of interphase death. The possibility of PDN originating from pyknosis-prone cells and the capacity of radiosensitive thymocytes to form autologous rosettes are discussed.