[Comparative study of the effects of thymalin and vitamin E on certain indices for local pulmonary protection in rheumatoid arthritis]. / Sravnitel'noe izuchenie vliianiia timalina i tokoferola atsetat na nekotorye pokazateli mestnoi zashchity legkykh pri revmatoidnom artrite.

In experimental rheumatoid arthritis, certain indices for local defence of the lung were studied together with effects on these of preparations of vitamin E and thymalin. Noted in experimental rheumatoid arthritis are manifest changes in quantitative indices for cellular population of the bronchoalveolar space and disturbances in humoral mechanisms of defence of the lungs. The drugs employed for the treatment of the affliction have a positive effect on quantitative indices for the cell population of the lung local defence factors. But no significant effects could be demonstrated of thymalin on humoral factors of defence of the lungs. Unlike thymalin, tocopheroli acetas is noted to augment the secretion of lysozyme, to decrease the activity of phospholipase A2, to improve the surface-active properties of the lung surfactant. It is suggested that its antioxidant, membrane-stabilizing action may be responsible for the positive effect on indices for local defence of the lung.

Effects of eicosapentaenoic and gamma-linolenic acids (dietary lipids) on pulmonary surfactant composition and function during porcine endotoxemia.

STUDY OBJECTIVES: To investigate whether a diet enriched with fish and borage oils, with their high polyunsaturated fatty acid (PUFA) content, alters surfactant composition and function during endotoxemia. DESIGN: Prospective, randomized, blinded, controlled animal study. SETTING: Research laboratory at a medical center. PARTICIPANTS: Thirty-six 15- to 25-kg, disease-free, castrated male pigs. DIETS AND MEASUREMENTS: Three groups of pigs (n = 12 per group) were fed for 8 days diets containing either omega-6 fatty acids (FAs) (corn oil; diet A), or omega-3 FAs (fish oil; diet B), or a combination of omega-6 and omega-3 FAs (borage and fish oils; diet C). Eight of 12 pigs in each group received a 0.1-mg/kg bolus of Escherichia coli endotoxin followed by a continuous infusion (0. 075 mg/kg/h). One lung was subsequently isolated ex vivo, and pressure-volume curves were measured. The contralateral lung was lavaged, and surfactant was analyzed for total and individual phospholipids and FA composition. Minimum and maximum surface tension was measured by bubble surfactometry. RESULTS: Pigs fed either diet B or C had increased oleic acid (C(18:1) omega-9), eicosapentaenoic acid (EPA; C(20:5) omega-3), docosahexaenoic acid (C(22:6) omega-3), and total omega-3 and monounsaturated FAs in their surfactant PUFA pools. The relative percentage of linoleic acid (C(18:2) omega-6) and total omega-6 FAs were significantly lower from pigs fed diets B and C compared with diet A. Palmitic acid (C(16:0)) concentrations, the primary FA in surfactant, had a tendency to be lower in pigs fed diets B and C. There were no demonstrable effects on surfactant function or pulmonary compliance. CONCLUSIONS: Diets containing EPA or EPA and gamma-linolenic acid altered the PUFA composition of pulmonary surfactant, but without demonstrable effects on surfactant function during porcine endotoxemia.

Effect of thyroid hormone (T3)-responsive changes in surfactant apoproteins on surfactant function during sepsis.

BACKGROUND: Long surfactant phospholipids are altered during sepsis; the role of surfactant apoproteins is unknown. This study investigates the effect of cecal ligation and puncture (CLP) on surfactant functional effectiveness and apoprotein transcriptional activity with or without T3 replacement. METHODS: Male Sprague Dawley rats underwent sham laparotomy or CLP with or without T3 replacement. Lung compliance, surfactant adsorption, and surface tension were measured with a surfactometer. Surfactant apoproteins A, B, and C (SP-A, SP-B, SP-C) mRNA was quantified by Northern blot analysis. RESULTS: Lung compliance was significantly decreased by sepsis; initial surface tension and adsorption values in CLP animals reflected apoprotein dysfunction. Sepsis decreased SP-A mRNA levels and increased SP-B mRNA; SP-C mRNA were unchanged. T3 treatment improved compliance, adsorption, and ST isotherms in septic animals. CONCLUSION: T3 attenuated sepsis-induced surfactant dysfunction and SP-A and SP-B transcriptional changes during sepsis. This suggests an interaction between the thyroid, surfactant apoproteins, and lung surfactant functional effectiveness and requires further study.

[The correction of the status of the pulmonary surfactant system as a method for preventing experimental pneumoconiosis]. / Korrektsiia sostoianiia surfaktantnoi sistemy legkikh kak metod profilaktiki éksperimental'nogo pnevmokonioza.

Using a model of experimental pneumoconiosis in albino rats, induced by breathing in a rock dust, we attempted correction of the pulmonary surfactant system, for which purpose we tried choline chloride as a drug preparation. The action of the above drug was found out to be depended upon the moment of its administration and time during which it is being administered, and is that of influence on both the concentration and mechanism of absorbtion of surface-active fractions of the surfactant in the liquid-gas interface. Early administration of choline chloride (during the dust factor exposure) increases concentration of those surfactants notable for their surface-active properties being maintained, and improves the processes of diffusion of surface-active substances, which observation is accompanied by decrease in intensity of the processes of fibroformation in the lung tissue. Choline chlorid employed on the discontinuation of the dust exposure has adverse effects leading to changes in the lipid composition, impairing the surface-active properties and processes of diffusion of the pulmonary surfactant, which fact may contribute to aggravation of fibrosis in the lungs.

Ambroxol. Alternativas de uso en neonatología / Ambroxol. therapy use in newborn

El ambroxol es un medicamento útil en el tratamiento del síndrome de dificultad respiratoria neonatal, dada su capacidad de elevar la producción y liberación de surfactante y de mejorar los mecanismos pulmonares. Por otro lado, previene la atelectasia pulmonar postextubación, adicionándose a las características anteriores su efecto mucolítico y mucocinético. En el presente trabajo se hace una revisión para ofrecer al lector una visión amplia del medicamento y sus posibles aplicaciones en pediatría. No se pretende sugerir que el ambroxol desplace las otras posibilidades terapéuticas, sino presentarlo como un medicamento que ofrece nuevas alternativas

Triiodothyronine (T3) supplementation maintains surfactant biochemical integrity during sepsis.

Surfactant functional effectiveness is dependent on phospholipid compositional integrity: sepsis decreases this through an undefined mechanism. Sepsis-induced hypothyroidism is commensurate and may be related. This study examines the effect of triiodothyronine (T3) supplementation on surfactant function, metabolism, and composition during sepsis. Male Sprague-Dawley rats (n = 75) underwent sham laparotomy or cecal ligation and puncture (CLP) with or without T3 supplementation (CLP/T3; 3 ng/hr). Twenty-four hours later, surfactant was obtained by lavage. Total phospholipids were determined by chromatography. Choline phosphate cytidyltransferase (CT) activity was determined by the formation of cytidine diphosphate (CDP)-choline. In vivo lung compliance was determined by lung inflation; surfactant hysteresis plots were determined on a pulsating bubble surfactometer. Lung compliance and surfactant hysteresis plots were significantly affected by sepsis; T3 modulated this (dynamic compliance: sham = 0.66 +/- 0.02, CLP = 0.47 +/- 0.06, CLP/T3 = 0.56 +/- 0.02 mm Hg/mL; p < 0.05). Sepsis produced a decrease in phosphatidylglycerol, and phosphatidic acid, with an increase in lesser surface active lipids phosphatidylserine and phosphatidylinositol. Hormonal replacement prevented these alterations. Lung CT activity was increased by sepsis independent of T3 treatment. Thyroid hormone may have an active role in lung functional preservation during sepsis caused by maintenance of surfactant biophysical and compositional homeostasis.

[Biochemical composition of a surfactant and its free radical processes in hyperbaric oxygenation and in the post-hyperoxic period]. / Biokhimicheskii sostav surfaktanta i svobodnoradikal'nye protsessy v nem pri giperbarooksigenatsii i v postgiperoksicheskii period.

Monitoring was made to examine the lungs. With this mode of hyperbaric oxygenation (0.3 MPa for 5 hours), rats developed mild oxygen intoxication which alleviated on day 3 and ceased on day 7 after its exposure. At the same time there were profound changes in the surfactant levels of protein, phospholipids, and cholesterol, which became normal on day 7 of postexposure. Chemiluminescence analysis and measurements of lipid peroxidation (PLO) products indicated that PLO rates in the surfactant decreased during hyperbaric oxygenation and remained at low levels within 24 hours of postexposure, whose cause might be activated by the antioxidative systems, as considered by the authors. However, on day 3 PLO enhances and on day 7 a new level of free-radical processes established, which was characterized by higher concentrations of free radicals and enhanced the activity of the antiradical systems.

Effect of pentoxifylline on the inhibition of surfactant synthesis induced by TNF-alpha in human type II pneumocytes.

Tumor necrosis factor alpha (TNF-alpha) seems to play an important role in the pathogenesis of the adult respiratory distress syndrome (ARDS). This study was designed to determine the effect of TNF-alpha and pentoxifylline (PTXF) on surfactant synthesis by isolated human type II pneumocytes. In order to isolate the pneumocytes, lungs obtained from both previously healthy multiple organ donors (n = 11) and patients who underwent surgical excision for lung cancer (n = 8) were used. Surfactant synthesis was measured by the incorporation of labeled glucose into the two most important phospholipid components of surfactant: phosphatidylcholine (PC) and phosphatidylglycerol (PGL). The pneumocytes of the donor group showed a greater degree of PC synthesis than those from the cancer group (3.44 +/- 0.19 versus 2.15 +/- 01.5 pmol/micrograms protein, p < 0.001). The synthesis of PC by pneumocytes in both the donor (1.13 +/- 0.19 versus 3.44 +/- 0.19 pmol/micrograms protein, p < 0.01) and cancer (0.99 +/- 0.11 versus 2.15 +/- 0.15 pmol/micrograms protein, p < 0.01) groups was decreased by TNF-alpha (100 ng/ml). This effect was blocked by PTXF (100 micrograms/ml), a substance that also increased PC production in the control-group pneumocytes from cancer patients, the final PC levels being similar to those of the donors in the absence of TNF-alpha. These results suggest that one of the mechanisms of TNF-alpha participation in the pathophysiology of ARDS is inhibition of surfactant synthesis, and support the hypothesis of in vivo production of TNF-alpha in lung-cancer patients, with subsequent chronic exposure of the lung epithelial cells to this cytokine.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of endotracheal bleomycin administration on phospholipid composition of rat lung surfactant.

The influence of intratracheal bleomycin instillation (10 mg x kg-1) on lung surfactant phospholipids in rats after 7 and 14 days from drug administration was evaluated. It was stated that bleomycin causes a great fall in phosphatidylcholine, disaturated phosphatidylcholine and phosphatidylglycerol content, both in extra- and intracellular pool of surfactant. The data thus presented evidenced that intratracheal bleomycin administration caused a profound changes in the lipid composition of rat lung surfactant.

Vitamin E alters alveolar type II cell phospholipid synthesis in oxygen and air.

Newborn rats were injected with vitamin E or placebo daily until 6 days after birth. The effect of vitamin E pretreatment on in vitro surfactant phospholipid synthesis was examined in isolated type II cells exposed to oxygen or air form 24 h in vitro. Type II cells were also isolated from untreated 6-day-old rats and cultured for 24 h in oxygen or air with control medium or vitamin E supplemented medium. These cells were used to examine the effect of vitamin E exposure in vitro on type II cell phospholipid synthesis and ultrastructure. Phosphatidylcholine (PC) synthesis was reduced in cells cultured in oxygen as compared with air. This decrease was not prevented by in vivo pretreatment or in vitro supplementation with vitamin E. Vitamin E pretreatment increased the ratio of disaturated PC to total PC and increased phosphatidylglycerol synthesis. The volume density of lamellar bodies in type II cells was increased in cells maintained in oxygen. Vitamin E did not affect the volume density of lamellar bodies. We conclude that in vitro hyperoxia inhibits alveolar type II cell phosphatidylcholine synthesis without decreasing lamellar body volume density and that supplemental vitamin E does not prevent hyperoxia-induced decrease in phosphatidylcholine synthesis.