Compuestos ciclopentenonas, procedimiento de obtención y su uso en la preparación de un medicamento útil para el tratamiento de enfermedades inflamatorias que cursan con procesos apoptómicos y fibróticos celulares

La invención describe unos compuestos ciclopentenonas, su procedimiento de obtención y su uso en la preparación de un medicamento útil para el tratamiento de una enfermedad que cursa con procesos inflamatorios, apoptóticos y fibróticos celularesPeer reviewedCIBER de Enfermedades Respiratorias, Universidad de La Laguna, Servicio Canario de Salud, Consejo Superior de Investigaciones CientíficasA1 Solicitud de patente con informe sobre el estado de la técnic

Compuestos ciclopentenonas, procedimiento de obtención y su uso en la preparación de un medicamento útil para el tratamiento de enfermedades inflamatorias que cursan con procesos apoptómicos y fibróticos celulares

La invención describe unos compuestos ciclopentenonas, su procedimiento de obtención y su uso en la preparación de un medicamento útil para el tratamiento de una enfermedad que cursa con procesos inflamatorios, apoptóticos y fibróticos celularesPeer reviewedCIBER de Enfermedades Respiratorias, Universidad de La Laguna, Servicio Canario de Salud, Consejo Superior de Investigaciones CientíficasB1 Patente sin examen previ

Compuestos ciclopentenonas, procedimiento de obtención y su uso en la preparación de un medicamento útil para el tratamiento de enfermedades inflamatorias que cursan con procesos apoptómicos y fibróticos celulares

[EN] The invention concerns cyclopentenone compounds, the method for obtaining them, and their use in the preparation of a drug used for treating diseases associated with cellular fibrotic, inflammatory and apoptotic processes.[FR] L'invention concerne des composés cyclopenténone, leur procédé d'obtention et leur utilisation pour la préparation d'un médicament utile pour le traitement d'une maladie associée à des processus inflammatoires, apoptotiques et fibrotiques cellulaires.[ES] La invención describe unos compuestos ciclopentenonas, su procedimiento de obtención y su uso en la preparación de un medicamento útil para el tratamiento de una enfermedad que cursa con procesos inflamatorios, apoptóticos y fibróticos celulares.Peer reviewedCiber de Enfermedades Respiratorioas, Universidad de La Laguna, Servicio Canario de Salud, Consejo Superior de Investigaciones CientíficasA1 Solicitud de patente con informe sobre el estado de la técnic

Compuestos ciclopentenonas, procedimiento de obtención y su uso en la preparación de un medicamento útil para el tratamiento de enfermedades inflamatorias que cursan con procesos apoptómicos y fibróticos celulares

[EN] The invention concerns cyclopentenone compounds, the method for obtaining them, and their use in the preparation of a drug used for treating diseases associated with cellular fibrotic, inflammatory and apoptotic processes.[FR] L'invention concerne des composés cyclopenténone, leur procédé d'obtention et leur utilisation pour la préparation d'un médicament utile pour le traitement d'une maladie associée à des processus inflammatoires, apoptotiques et fibrotiques cellulaires.[ES] La invención describe unos compuestos ciclopentenonas, su procedimiento de obtención y su uso en la preparación de un medicamento útil para el tratamiento de una enfermedad que cursa con procesos inflamatorios, apoptóticos y fibróticos celulares.Peer reviewedCiber de Enfermedades Respiratorioas, Universidad de La Laguna, Servicio Canario de Salud, Consejo Superior de Investigaciones CientíficasA1 Solicitud de patente con informe sobre el estado de la técnic

Tryptase is involved in the development of early ventilator-induced pulmonary fibrosis in sepsis-induced lung injury

Introduction: Most patients with sepsis and acute lung injury require mechanical ventilation to improve oxygenation and facilitate organ repair. Mast cells are important in response to infection and resolution of tissue injury. Since tryptase secreted from mast cells has been associated with tissue fibrosis, we hypothesized that tryptase would be involved in the early development of ventilator-induced pulmonary fibrosis in a clinically relevant model of sepsis-induced lung injury. Methods: Prospective, randomized, controlled animal study using Sprague-Dawley rats. Sepsis was induced by cecal ligation and perforation. Animals were randomized to spontaneous breathing or two ventilatory strategies for 4 h: protective ventilation with tidal volume (VT) = 6 ml/kg plus 10 cmH2O positive end-expiratory pressure (PEEP) or injurious ventilation with VT = 20 ml/kg plus 2 cmH2O PEEP. Healthy, non-ventilated animals served as non-septic controls. We studied the following end points: histology, serum cytokine levels, hydroxyproline content, tryptase and proteinase-activated receptor-2 (PAR-2) protein level in lung homogenates, and tryptase and PAR-2 immunohistochemical localization in the lungs. Results: All septic animals developed acute lung injury. Animals ventilated with high VT had a significant increase of pulmonary fibrosis, hydroxyproline content, tryptase and PAR-2 protein levels compared to septic controls (P <0.0001). However, protective ventilation attenuated sepsis-induced lung injury and decreased lung tryptase and PAR-2 protein levels. Immunohistochemical staining confirmed the presence of tryptase and PAR-2 in the lungs. Conclusions: Mechanical ventilation modified tryptase and PAR-2 in injured lungs. Increased levels of these proteins were associated with development of sepsis and ventilator-induced pulmonary fibrosis early in the course of sepsis-induced lung injury

Tryptase is involved in the development of early ventilator-induced pulmonary fibrosis in sepsis-induced lung injury

Abstract Introduction Most patients with sepsis and acute lung injury require mechanical ventilation to improve oxygenation and facilitate organ repair. Mast cells are important in response to infection and resolution of tissue injury. Since tryptase secreted from mast cells has been associated with tissue fibrosis, we hypothesized that tryptase would be involved in the early development of ventilator-induced pulmonary fibrosis in a clinically relevant model of sepsis-induced lung injury. Methods Prospective, randomized, controlled animal study using Sprague-Dawley rats. Sepsis was induced by cecal ligation and perforation. Animals were randomized to spontaneous breathing or two ventilatory strategies for 4 h: protective ventilation with tidal volume (VT) = 6 ml/kg plus 10 cmH2O positive end-expiratory pressure (PEEP) or injurious ventilation with VT = 20 ml/kg plus 2 cmH2O PEEP. Healthy, non-ventilated animals served as non-septic controls. We studied the following end points: histology, serum cytokine levels, hydroxyproline content, tryptase and proteinase-activated receptor-2 (PAR-2) protein level in lung homogenates, and tryptase and PAR-2 immunohistochemical localization in the lungs. Results All septic animals developed acute lung injury. Animals ventilated with high VT had a significant increase of pulmonary fibrosis, hydroxyproline content, tryptase and PAR-2 protein levels compared to septic controls (P <0.0001). However, protective ventilation attenuated sepsis-induced lung injury and decreased lung tryptase and PAR-2 protein levels. Immunohistochemical staining confirmed the presence of tryptase and PAR-2 in the lungs. Conclusions Mechanical ventilation modified tryptase and PAR-2 in injured lungs. Increased levels of these proteins were associated with development of sepsis and ventilator-induced pulmonary fibrosis early in the course of sepsis-induced lung injury

An aqueous pomegranate peel extract (Punica granatum) protect against Elastase-induced pulmonary emphysema in Sprague Dawley rats model

We investigated the effect of Punica granatum peel aqueous extract (PGE), on pulmonary inflammation and alveolar degradation induced by intratracheal administration of Elastase in Sprague Dawley rats. Lung inflammation was induced in rats by intratracheal instillation of Elastase. On day 1 and 2, animals received an intraperitoneal injection of PGE (200 mg/mL), three hours later, they were intratracheally instilled with 25U/kg pancreatic porcine Elastase. Animals were sacrificed 7 days later. Bronchoalveolar lavage (BAL) were collected and cellularity, histology and mRNA expression of Monocyte chemotactic protein 1(MCP-1), Tumor Necrosis Factor-Alpha (TNF-α), Interleukin 6 (IL-6), and Matrix Metalloproteinase-2 (MMP-2) were studied. In addition, activity of TNF- α, IL-6 and MCP-1 on BAL were also analyzed byELISA Kit. Elastase administration increased: BAL cellularity, neutrophils recruitment and BAL MCP1, IL-6 expressions. It also increased lung TNF-α, MCP-1, MMP-2 expressions, platelets recruitment, histological parameters at 7th day of elastase treatment. Intraperitoneal injection of 200 mg/kg of PGE reduced, significantly, BAL cellularity, and neutrophils recruitment. However, in animal treated with PGE, MCP-1, MMP-2 and IL-6 on day 7, were similar to the Sham group. Treatment with PGE (200 mg/kg) also significantly reduced lung TNF-α, and MCP-1 expression. This study reveals that PGE Punica granatum protects against elastase lung inflammation and alveolar degradation induced in rats

Systemic Effects Induced by Hyperoxia in a Preclinical Model of Intra-abdominal Sepsis

Supplemental oxygen is a supportive treatment in patients with sepsis to balance tissue oxygen delivery and demand in the tissues. However, hyperoxia may induce some pathological effects. We sought to assess organ damage associated with hyperoxia and its correlation with the production of reactive oxygen species (ROS) in a preclinical model of intra-abdominal sepsis. For this purpose, sepsis was induced in male, Sprague-Dawley rats by cecal ligation and puncture (CLP). We randomly assigned experimental animals to three groups: control (healthy animals), septic (CLP), and sham-septic (surgical intervention without CLP). At 18 h after CLP, septic (n=39), sham-septic (n=16), and healthy (n=24) animals were placed within a sealed Plexiglas cage and randomly distributed into four groups for continuous treatment with 21%, 40%, 60%, or 100% oxygen for 24 h. At the end of the experimental period, we evaluated serum levels of cytokines, organ damage biomarkers, histological examination of brain and lung tissue, and ROS production in each surviving animal. We found that high oxygen concentrations increased IL-6 and biomarkers of organ damage levels in septic animals, although no relevant histopathological lung or brain damage was observed. Healthy rats had an increase in IL-6 and aspartate aminotransferase at high oxygen concentration. IL-6 levels, but not ROS levels, are correlated with markers of organ damage. In our study, the use of high oxygen concentrations in a clinically relevant model of intra-abdominal sepsis was associated with enhanced inflammation and organ damage. These findings were unrelated to ROS release into circulation. Hyperoxia could exacerbate sepsis-induced inflammation, and it could be by itself detrimental. Our study highlights the need of developing safer thresholds for oxygen therapy