Protective effects of Surfacen® in allergen-induced asthma mice model.

Airway obstruction with increased airway resistance in asthma, commonly caused by smooth muscle constriction, mucosal edema and fluid secretion into the airway lumen, may partly be due to a poor function of pulmonary surfactant. Surfacen®, a clinical pulmonary surfactant, has anti-inflammatory action, but its effect on asthma has not been studied. This work aimed to evaluate the effect of Surfacen® in a murine allergen-induced acute asthma model, using house dust mite allergens. In a therapeutic experimental setting, mice were first sensitized by being administered with two doses (sc) of Dermatophagoides siboney allergen in aluminum hydroxide followed by one intranasal administration of the allergen. Then, sensitized mice were administered with aerosol of hypertonic 3% NaCl, Salbutamol 0.15 mg/kg, or Surfacen® 16 mg in a whole-body chamber on days 22, 23, and 24. Further, mice were subjected to aerosol allergen challenge on day 25. Surfacen® showed bronchial dilation and inhibition of Th2 inflammation (lower levels of IL-5 and IL-13 in broncoalveolar lavage) which increased IFN-γ and unchanged IL-10 in BAL. Moreover, Sufacen® administration was associated with a marked inhibition of the serum specific IgE burst upon allergen exposure, as well as, IgG2a antibody increase, suggesting potential anti-allergy effects with inclination towards Th1. These results support also the effectiveness of the aerosol administration method to deliver the drug into lungs. Surfacen® induced a favorable pharmacological effect, with a bronchodilator outcome comparable to Salbutamol, consistent with its action as a lung surfactant, and with an advantageous anti-inflammatory and anti-allergic immunomodulatory effect.

Inhibition and counterinhibition of Surfacen, a clinical lung surfactant of natural origin.

Inactivation of pulmonary surfactant by different components such as serum, cholesterol or meconium contributes to severe respiratory pathologies through destabilization and collapse of airspaces. Recent studies have analyzed in detail how the interfacial properties of natural surfactant purified from animal lungs are altered as a consequence of its exposure to serum proteins or meconium-mobilized cholesterol. It has been also demonstrated that pre-exposure of surfactant to polymers such as hyaluronic acid provides resistance to inactivation by multiple inhibitory agents. In the current work, we have extended these studies to the analysis of Surfacen, a clinical surfactant currently in use to rescue premature babies suffering or at risk of respiratory distress due to congenital lack of surfactant. This surfactant is also strongly inhibited by both meconium and serum when tested in the captive bubble surfactometer (CBS) under conditions mimicking respiratory dynamics. As it occurs with native surfactant, Surfacen is markedly protected from inhibition by pre-exposure to hyaluronic acid, confirming that clinical surfactants can be improved to treat pathologies associated with strongly deactivating contexts, such as those associated with lung injury and inflammation. Remarkably, we found that, under physiologically-mimicking conditions, a cholesterol-free clinical surfactant such as Surfacen is less susceptible to inhibition by cholesterol-mobilizing environments than cholesterol-containing natural surfactant, as a consequence of a markedly reduced susceptibility to incorporation of exogenous cholesterol.

Interfacial behavior and structural properties of a clinical lung surfactant from porcine source.

Surfacen® is a clinical surfactant preparation of porcine origin, partly depleted of cholesterol, which is widely used in Cuba to treat pre-term babies at risk or already suffering neonatal respiratory distress. In the present study we have characterized the interfacial behavior of Surfacen in several in vitro functional models, including spreading and compression-expansion cycling isotherms in surface balances and in a captive bubble surfactometer, in comparison with the functional properties of whole native surfactant purified from porcine lungs and its reconstituted organic extract, the material from which Surfacen is derived. Surfacen exhibited similar properties to native porcine surfactant or its organic extract to efficiently form stable surface active films at the air-liquid interface, able to consistently reach surface tensions below 5mN/m upon repetitive compression-expansion cycling. Surfacen films, however, showed a substantially larger and stable compression-driven segregation of condensed lipid phases than exhibited by films formed by native surfactant or its organic extract. In spite of structural differences observed at microscopic level, Surfacen membranes showed a similar thermotropic behavior to membranes from native surfactant or its organic extract, characterized by calorimetry or fluorescence spectroscopy of samples doped with the Laurdan probe. On the other hand, analysis by atomic force microscopy of films formed by Surfacen or by the organic extract of native porcine surfactant revealed a similar network of interconnected condensed nanostructures, suggesting that the organization of the films at the submicroscopic level is the essential feature to support the proper stability and mechanical properties permitting the interfacial surfactant films to facilitate the work of breathing.

In vitro activity of the clinical pulmonary surfactant Surfacen® against Leishmania amazonensis.

Surfacen® is an exogenous natural lung surfactant, composed by phospholipids and hydrophobic proteins, which is applied successfully in Newborn Respiratory Distress Syndrome. In this paper, in vitro activity of Surfacen® against Leishmania amazonensis is described. The product showed activity against the amastigote form found in peritoneal macrophages from BALB/c mice, with an IC50 value of 17.9 ± 3.0 µg/mL; while no toxic effect on host cell was observed up to 200 µg/mL. This is the first report about the antileishmanial activity of Surfacen®.

In vitro activity of the clinical pulmonary surfactant Surfacen® against Leishmania amazonensis / Actividad in vitro de surfactante pulmonar clínico Surfacen® frente a Leishmania amazonensis

Surfacen® is an exogenous natural lung surfactant, composed by phospholipids and hydrophobic proteins, which is applied successfully in Newborn Respiratory Distress Syndrome. In this paper, in vitro activity of Surfacen® against Leishmania amazonensis is described. The product showed activity against the amastigote form found in peritoneal macrophages from BALB/c mice, with an IC50 value of 17.9 ± 3.0 µg/mL; while no toxic effect on host cell was observed up to 200 µg/mL. This is the first report about the antileishmanial activity of Surfacen®.

Surfacen® es un surfactante natural exógeno extraído del pulmón, formado por fosfolípidos y proteínas hidrofóbicas, el cual es aplicado con éxito en el Síndrome de Distrés Respiratorio en Niños Recién Nacidos. En este trabajo, se describe la actividad in vitro del Surfacen® contra Leishmania amazonensis. El producto mostró actividad frente a amastigotes que se encuentran en macrófagos peritoneales de ratón BALB/c, con una CI50 de 17.9 ± 3.0 µg/mL, mientras no se observaron efectos tóxicos sobre la célula hospedera hasta 200 µg/mL. Este estudio constituye el primer reporte sobre la actividad antileishmania del Surfacen®.

Caracterización de neonatos con peso inferior a 2000 g / Characterization of newborns with a birth weight under 2000 g

Introducción. Los niños con bajo peso al nacer son 20 veces más propensos a morir y presentan mayor morbilidad que los nacidos con buen peso. El objetivo de la presente investigación fue caracterizar a los recién nacidos con peso inferior a 2000 g, nacidos entre el 1ro. de enero del 2005 y el 31 de diciembre del 2006 en el Hospital Universitario América Arias. Métodos. Se realizó un estudio observacional, descriptivo-analítico, longitudinal y prospectivo, cuyo universo fueron los neonatos con peso inferior a 2000 g, nacidos en este período. En el análisis estadístico se utilizó la distribución de frecuencias, la media y la desviación estándar de la ganancia de peso, la talla, y las circunferencias cefálica y braquial. Resultados. El 96,16 por ciento de los pacientes estudiados nacieron con peso entre 1000 y 1999 g. El 93,27 por ciento estuvo por debajo de las 36,6 semanas de gestación y en el 75,96 por ciento de los casos el parto fue distócico. El 61,54 por ciento de los neonatos tuvo peso adecuado para su edad gestacional. Predominaron los pacientes con factores de riesgo asociados. Más de la mitad presentó morbilidad asociada, principalmente por sepsis (25,96 por ciento). Falleció el 10,58 por ciento de los recién nacidos. Conclusiones. Las principales causas del bajo peso de los recién nacidos fueron el embarazo múltiple y la enfermedad hipertensiva de la gestación. Las defunciones se comportaron por debajo de lo esperado. En los pacientes con crecimiento intrauterino retardado simétricos, la ganancia de peso y talla al alta fue significativamente mayor que en los asimétricos y adecuados para su edad gestacional.

Introduction. Children with low birth weight are 20 times more prone to die and to have a greater morbidity than those with an adequate weight. The objective of this research was to characterize the newborn infants with a weight lower than 2000 g that were born between January 1st, 2005 and December 31st , 2006 in America Arias Children Hospital. Methods: An observational, descriptive, analytic, longitudinal and prospective study was carried out among newborn infants with a birth weight under 2000 g that were born during this period. In the statistical analysis, frequency distribution, mean and standard deviation of weight gain, height, and cephalic and brachial circunferences were used. Results. 96.16 percent of the studied patients were born with a birth weight between 1000 and 1999 g. 93.27 percentpercentwere below the 36.6 weeks of pregnancy, and in 75.96 percent of the cases, delivery was dystocic. 61.54 percent of the newborn infants had a weight according to its gestational age. There was a predominance of patients with associated risk factors. More than half had an associated morbidity, due mainly to sepsis (25.96 percent). 10.58 percent of the newborn died. Conclusions. The main causes of the low weight of newborns were multiple pregnancy and hipertensive disease during gestation. Deaths were lower than expected. In patients with a symmetric retarded intrauaterine growth, weigh gain and height on discharge were significantly higher than in the asymmetric and they proved to be adequate for their gestational age.

Biochemical and pharmacological differences between preparations of exogenous natural surfactant used to treat Respiratory Distress Syndrome: role of the different components in an efficient pulmonary surfactant.

The pharmaceutical application of exogenous natural pulmonary surfactant preparations has shown its efficiency in the therapeutical treatment of infants with Respiratory Distress Syndrome. At the same time, the use of these preparations in patients with Acute Respiratory Distress Syndrome, although not still an effective therapy, shows promising results. The analysis of composition, structure and surface activity of some of the different natural surfactant preparations available today for clinical use reveals important differences, a fact that opens horizons in the optimization of new effective formulations in the treatment of the Acute Respiratory Distress Syndrome. The purpose of this review is to carry out an updating of the current models interpreting the role of the main components of pulmonary surfactant as a reference to evaluate the biochemical composition of the preparations of exogenous natural pulmonary surfactant currently in use and their apparent pharmacological effect.