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.

Mecanismos inmunológicos e infertilidad femenina / Immune mechanisms and female infertility

Introducción: la infertilidad es un problema de salud mundial en aumento. Sus factores causales relacionados con el sexo femenino son mayoritarios. Recientemente se ha planteado una fuerte asociación entre los trastornos de la fertilidad y las alteraciones funcionales del sistema inmune, que contribuyen al origen y mantenimiento de la infertilidad.Objetivo: identificar en la literatura científica actualizada la contribución de los mecanismos inmunológicos en el desarrollo de la infertilidad femenina.Desarrollo: los mismos componentes inmunitarios que garantizan el éxito de la reproducción, pueden generar un entorno inflamatorio perpetuado, ante un estímulo antigénico, que produce lesión tisular. La inflamación desregulada repercute en reacciones autoinmunes contra las estructuras del aparato reproductor, y afectan su funcionalidad. La presencia de autoanticuerpos y citocinas proinflamatorias, como marcadores biológicos de estos fenómenos, ha sido reportada en entidades como la endometriosis y el síndrome de ovario poliquístico.Conclusiones: aunque se ha señalado que el sistema inmune desempeña un importante rol en el desarrollo de la reproducción femenina normal y patológica, el conocimiento obtenido en esta área sigue siendo exiguo. La subestimación de los factores inmunitarios en el escenario clínico muchas veces omite posibles alternativas diagnósticas y terapéuticas, que pudieran contribuir a incrementar la calidad del enfoque asistencial a las mujeres infértiles. La complejidad de los sistemas inmune y endocrino, y el corto alcance de las herramientas diagnósticas disponibles, son factores que contribuyen a esta insuficiencia(AU)

Introduction: infertility is a growing worldwide health problem whose causal factors are mostly associated to the female sex. A close relationship has recently been suggested between fertility disorders and functional alterations of the immune system contributing to and maintaining infertility.Objective: review updated scientific literature about the subject to identify the role of immune mechanisms in the development of female infertility.Development: the very immune components ensuring the success of reproduction may create a perpetuated inflammatory environment in the presence of an antigenic stimulus, resulting in the development of a tissular lesion. Dysregulated inflammation triggers autoimmune reactions against reproductive structures, affecting their operation. The presence of autoantibodies and proinflammatory cytokines as biological markers of these phenomena has been reported for conditions such as endometriosis and polycystic ovary syndrome.Conclusions: the immune system is known to play an important role in both normal and pathological female reproduction. However, information about the subject continues to be scant. Underestimation of the immune factors present in the clinical environment often blocks the way for diagnostic and therapeutic alternatives which could otherwise improve the quality of the care of infertile women. The complexity of the immune and endocrine systems, as well as the limited reach of the available diagnostic tools, are factors contributing to such insufficiency.

Mecanismos inmunológicos e infertilidad femenina / Immune mechanisms and female infertility

Introducción: La infertilidad es un problema de salud mundial en aumento. Sus factores causales relacionados con el sexo femenino son mayoritarios. Recientemente se ha planteado una fuerte asociación entre los trastornos de la fertilidad y las alteraciones funcionales del sistema inmune, que contribuyen al origen y mantenimiento de la infertilidad.Objetivo: identificar en la literatura científica actualizada la contribución de los mecanismos inmunológicos en el desarrollo de la infertilidad femenina.Desarrollo: los mismos componentes inmunitarios que garantizan el éxito de la reproducción, pueden generar un entorno inflamatorio perpetuado, ante un estímulo antigénico, que produce lesión tisular. La inflamación desregulada repercute en reacciones autoinmunes contra las estructuras del aparato reproductor, y afectan su funcionalidad. La presencia de autoanticuerpos y citocinas proinflamatorias, como marcadores biológicos de estos fenómenos, ha sido reportada en entidades como la endometriosis y el síndrome de ovario poliquístico.Conclusiones: aunque se ha señalado que el sistema inmune desempeña un importante rol en el desarrollo de la reproducción femenina normal y patológica, el conocimiento obtenido en esta área sigue siendo exiguo. La subestimación de los factores inmunitarios en el escenario clínico muchas veces omite posibles alternativas diagnósticas y terapéuticas, que pudieran contribuir a incrementar la calidad del enfoque asistencial a las mujeres infértiles. La complejidad de los sistemas inmune y endocrino, y el corto alcance de las herramientas diagnósticas disponibles, son factores que contribuyen a esta insuficiência(AU)

Introduction: Infertility is a growing worldwide health problem whose causal factors are mostly associated to the female sex. A close relationship has recently been suggested between fertility disorders and functional alterations of the immune system contributing to and maintaining infertility.Objective: review updated scientific literature about the subject to identify the role of immune mechanisms in the development of female infertility.Development: the very immune components ensuring the success of reproduction may create a perpetuated inflammatory environment in the presence of an antigenic stimulus, resulting in the development of a tissular lesion. Dysregulated inflammation triggers autoimmune reactions against reproductive structures, affecting their operation. The presence of autoantibodies and proinflammatory cytokines as biological markers of these phenomena has been reported for conditions such as endometriosis and polycystic ovary syndrome.Conclusions: the immune system is known to play an important role in both normal and pathological female reproduction. However, information about the subject continues to be scant. Underestimation of the immune factors present in the clinical environment often blocks the way for diagnostic and therapeutic alternatives which could otherwise improve the quality of the care of infertile women. The complexity of the immune and endocrine systems, as well as the limited reach of the available diagnostic tools, are factors contributing to such insufficiency(AU)

Safety of the production process of SURFACEN(®) to inactivate and remove virus.

SURFACEN(®) is a biological product produced from pig lungs. Since these animals can be potential sources of microbial pathogens such as viruses, the manufacturing process of this product should guarantee safety from health hazards. The SURFACEN(®) production procedure is capable of effective viral clearance (inactivation/removal) by involving two stages of organic solvent extraction followed by acetone precipitation and heat treatment. In this study, we evaluated the clearance capacity of these four stages for a wide range of viruses by performing spiking experiments. Residual contamination was assessed using a Tissue Culture Infectious Dose assay (log10 TCID50). The validation study demonstrated that, for all viruses tested, the TCID50 titers were reduced by more than 2 log10 in each stage. Total log reduction values achieved were between ≥17.82 log10 and ≥27.93 log10, depending on the virus physical properties, titer, and the number of processing stages applied. Results indicated that the production procedure of SURFACEN(®) can inactivate or remove contaminant viruses from the raw material.

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®.