Impacto de la modificación de la respuesta inmunitaria por la lisofosfatidilcolina en la eficacia de la terapia antibiótica en un modelo experimental de sepsis peritoneal y de neumonía por Pseudomonas aeruginosa

Introduction: Immune response stimulation may be an adjuvant to antimicrobial treatment. Here, we evaluated the impact of immune response modification by lysophosphatidylcholine (LPC), combined with imipenem or ceftazidime, in murine models of peritoneal sepsis (PS) and pneumonia induced by Pseudomonas aeruginosa. Methods: The imipenem and ceftazidime-susceptible strain (Pa39) and imipenem and ceftazidime- resistant strain (Pa238) were used. Ceftazidime pharmacokinetic and pharmacodynamic parameters were determined. The therapeutic efficacy and TNF- and IL-10 levels were determined in murine mod- els of PS and pneumonia induced by Pa39 and Pa238 and treated with LPC, imipenem or ceftazidime, alone or in combination. Results: In the PS model, LPC+ceftazidime reduced spleen and lung Pa238 concentrations (−3.45 and −3.56 log10 CFU/g; P < 0.05) to a greater extent than ceftazidime monotherapy, while LPC + imipenem maintained the imipenem efficacy (−1.66 and −1.45 log10 CFU/g; P > 0.05). In the pneumonia model, LPC + ceftazidime or LPC + imipenem reduced the lung Pa238 concentrations (−2.37 log10 CFU/g, P = 0.1, or −1.35 log10 CFU/g, P = 0.75). For Pa39, no statistically significant difference was observed in the PS and pneumonia models between combined therapy and monotherapy. Moreover, LPC + imipenem and LPC+ceftazidime significantly decreased and increased the TNF- and IL-10 levels, respectively, in com- parison with the untreated controls and monotherapies. Conclusions: These results demonstrate the impact of immune response modification by LPC plus antibiotics on the prognosis of infections induced by ceftazidime-resistant P. aeruginosa.introducción: La estimulación de la respuesta inmunitaria podría ser adyuvante al tratamiento antimi- crobiano. En este estudio, hemos evaluado el impacto de la modificación de la respuesta inmunitaria por la lisofosfatidilcolina (LPC), combinada con imipenem ó ceftazidima, en modelos murinos de sepsis peritoneal (SP) y de neumonía por Pseudomonas aeruginosa (P. aeruginosa).Métodos: La cepa sensible a imipenem y ceftazidima (Pa39) y la cepa resistente a ambos antibióticos (Pa238) fueron usadas. Los parámetros farmacocinéticos/farmacodinámicos de ceftazidima fueron deter- minados. La eficacia terapéutica y los niveles de TNF- and IL-10 fueron determinados en los modelos murinos de SP y de neumonía por Pa39 y Pa238 y tratados con LPC, imipenem o ceftazidima, en monoter- apia ó en combinación. Resultados: En el modelo de SP, LPC + ceftazidima redujo la concentración de Pa238 en el bazo y el pulmón (–3,45 y –3,56 log10 UFC/g; p < 0,05) en comparación con ceftazidima, mientras LPC + impenem mantuvo la eficacia de imipenem (–1,66 y –1,45 log10 UFC/g; p > 0,05). En el modelo de neumonía, LPC + ceftazidima o LPC + imipenem redujo la concentración de Pa238 en pulmón (–2,37 log10 UFC/g, p = 0,1 o –1,35 log10 UFC/g, p = 0,75). Para Pa39, no se observó diferencia estadística significativa entre la terapia combinada y la monoterapia en los modelos de SP y de neumonía. Además, LPC + imipenem y LPC + ceftazidime redujeron y aumentaron los niveles de TNF- y IL-10, respectivamente, en comparación con los controles no tratados y las monoterapias. Conclusiones: Estos resultados demuestran el impacto de la modificación de la respuesta inmunitaria por LPC en combinación con antibióticos en el pronóstico de las infecciones por P. aeruginosa ceftazidima- resistente

Clinical utility of urinary gluten immunogenic peptides in the follow-up of patients with coeliac disease

[Background] Gluten-free diet (GFD) is the only treatment for patients with coeliac disease (CD) and its compliance should be monitored to avoid cumulative damage.[Aims] To analyse gluten exposures of coeliac patients on GFD for at least 24 months using different monitoring tools and its impact on duodenal histology at 12-month follow-up and evaluate the interval of determination of urinary gluten immunogenic peptides (u-GIP) for the monitoring of GFD adherence.[Methods] Ninety-four patients with CD on a GFD for at least 24 months were prospectively included. Symptoms, serology, CDAT questionnaire, and u-GIP (three samples/visit) were analysed at inclusion, 3, 6, and 12 months. Duodenal biopsy was performed at inclusion and 12 months.[Results] At inclusion, 25.8% presented duodenal mucosal damage; at 12 months, this percentage reduced by half. This histological improvement was indicated by a reduction in u-GIP but did not correlate with the remaining tools. The determination of u-GIP detected a higher number of transgressions than serology, regardless of histological evolution type. The presence of >4 u-GIP-positive samples out of 12 collected during 12 months predicted histological lesion with a specificity of 93%. Most patients (94%) with negative u-GIP in ≥2 follow-up visits showed the absence of histological lesions (p < 0.05).[Conclusion] This study suggests that the frequency of recurrent gluten exposures, according to serial determination of u-GIP, could be related to the persistence of villous atrophy and that a more regular follow-up every 6 months, instead of annually, provides more useful data about the adequate adherence to GFD and mucosal healing.This study was funded in part by Fundación Progreso y Salud, Consejería de Salud, Junta de Andalucía (PI-0427-2017 and PI-0053-2018).Peer reviewe

GEODIVULGAR: Geología y Sociedad

Fac. de Ciencias GeológicasFALSEsubmitte

Impact of the immune response modification by lysophosphatidylcholine in the efficacy of antibiotic therapy of experimental models of peritoneal sepsis and pneumonia by Pseudomonas aeruginosa: LPC therapeutic effect in combined therapy.

Immune response stimulation may be an adjuvant to antimicrobial treatment. Here, we evaluated the impact of immune response modification by lysophosphatidylcholine (LPC), combined with imipenem or ceftazidime, in murine models of peritoneal sepsis (PS) and pneumonia induced by Pseudomonas aeruginosa. The imipenem and ceftazidime-susceptible strain (Pa39) and imipenem and ceftazidime-resistant strain (Pa238) were used. Ceftazidime pharmacokinetic and pharmacodynamic parameters were determined. The therapeutic efficacy and TNF-α and IL-10 levels were determined in murine models of PS and pneumonia induced by Pa39 and Pa238 and treated with LPC, imipenem or ceftazidime, alone or in combination. In the PS model, LPC+ceftazidime reduced spleen and lung Pa238 concentrations (-3.45 and -3.56log10CFU/g; P0.05). In the pneumonia model, LPC+ceftazidime or LPC+imipenem reduced the lung Pa238 concentrations (-2.37log10CFU/g, P=0.1, or -1.35log10CFU/g, P=0.75). For Pa39, no statistically significant difference was observed in the PS and pneumonia models between combined therapy and monotherapy. Moreover, LPC+imipenem and LPC+ceftazidime significantly decreased and increased the TNF-α and IL-10 levels, respectively, in comparison with the untreated controls and monotherapies. These results demonstrate the impact of immune response modification by LPC plus antibiotics on the prognosis of infections induced by ceftazidime-resistant P. aeruginosa

Long non-coding RNA H19 as a biomarker for hepatocellular carcinoma

[Background and Aims] Liver cancer stem cells (CSCs) could be involved in the carcinogenesis, recurrence, metastasis and chemoresistance of hepatocellular carcinoma (HCC). The aim of this study was to explore the role of lncRNA-H19 as a biomarker for liver cancer.[Methods] LncRNA-H19 expression levels and the functional assays were conducted in EpCAM+CD133+ CSCs and C57BL/6J mice fed with a high-fat high-cholesterol carbohydrate (HFHCC) or standard diet for 52 weeks. Liver tissue and plasma samples from patients with cirrhosis, with or without HCC, were used for the analyses of gene expression and circulating lncRNA-H19 levels in an estimation and validation cohort.[Results] EpCAM+CD133+ cells showed a stem cell-like phenotype, self-renewal capacity, upregulation of pluripotent gene expression and overexpressed lncRNA-H19 (p < .001). Suppression of lncRNA-H19 by antisense oligonucleotide treatment significantly reduced the self-renewal capacity (p < .001). EpCAM, CD133 and lncRNA-h19 expression increased accordingly with disease progression in HFHCC-fed mice (p < .05) and also in liver tissue from HCC patients (p = .0082). Circulating lncRNA-H19 levels were significantly increased in HCC patients in both cohorts (p = .013; p < .0001). In addition, lncRNA-H19 levels increased accordingly with BCLC staging (p < .0001) and decreased after a partial and complete therapeutic response (p < .05). In addition, patients with cirrhosis who developed HCC during follow-up showed higher lncRNA-H19 levels (p = .0025).[Conclusion] LncRNA-H19 expression was increased in CSCs, in liver tissue and plasma of patients with HCC and decreased after partial/complete therapeutic response. Those patients who developed HCC during the follow-up showed higher levels of lncRNA-H19. LncRNA-H19 could constitute a new biomarker of HCC.The research leading to these results has received funding from the Ministry of Health of the Government of Andalusia under grant agreement PC-0033-2017 and from the Instituto de Salud Carlos III under grant agreements PI16/01842, PI19/01404 and PI19/00589. Ángela Rojas has received the Sara Borrell postdoctoral fellowships from Instituto de Salud Carlos III CD18/00126 to support her postdoctoral contract.Peer reviewe

Desarrollo de la expresión oral en la ESO desde la participación activa del alumnado en las diferentes áreas

El dominio de la expresión oral influye en las bases de un buen aprendizaje. Por ello el objeto de este proyecto es fomentar el aprendizaje de los procedimientos relacionados con la exposición y familiarizarse con sus componentes: título, tema, introducción, desarrollo, documentación y conclusión. Otros objetivos son analizar los elementos de la comunicación no verbal, desarrollar la expresión oral y dotar de coherencia la creación de textos. Las estrategias que ponen en práctica para llevar a cabo el trabajo son el diálogo, la investigación bibliográfica, el coloquio, el debate, la declamación, la dramatización, el taller literario y el libro-forum. La metodología consiste en preparar una exposición, tanto individual, como por parejas, como en grupo, grabarla y evaluar el resultado. En la evaluación se hace especial hincapié en el control de la expresión oral. Incluye memoria de las actividades desarrolladas por los departamentos..Madrid (Comunidad Autónoma). Consejería de Educación. Dirección General de Mejora de la Calidad de la EnseñanzaMadridMadrid (Comunidad Autónoma). Subdirección General de Formación del Profesorado. CRIF Las Acacias; General Ricardos 179 - 28025 Madrid; Tel. + 34915250893ES

Guia de pràctica clínica sobre el maneig i tractament d’úlceres d’extremitats inferiors

Úlceres; Extremitats inferiors; Cures; EpidemiologiaÚlceras; Extremidades inferiores; Curas; EpidemiologíaUlcers; Lower extremities; Cures; EpidemiologyLes úlceres cròniques en les extremitats inferiors són un problema de salut amb importants repercussions socioeconòmiques a causa de la seva llarga evolució. Pot minvar la qualitat de vida del pacient i propiciar l’absentisme laboral, i constitueix un gran repte per als professionals sanitaris. L'objectiu d'aquest document és oferir al professional un coneixement actualitzat sobre les millors actuacions preventives i curatives en el maneig i tractament de les úlceres d’extremitat inferior. També facilitar informació sobre mesures diagnòstiques i terapèutiques per a cada situació clínica, per poder millorar la qualitat i eficiència de les cures proporcionades des d'una perspectiva holística i individualitzada

Guia de pràctica clínica sobre el maneig i tractament d’úlceres d’extremitats inferiors

Úlceres; Extremitats inferiors; Cures; EpidemiologiaÚlceras; Extremidades inferiores; Curas; EpidemiologíaUlcers; Lower extremities; Cures; EpidemiologyLes úlceres cròniques en les extremitats inferiors són un problema de salut amb importants repercussions socioeconòmiques a causa de la seva llarga evolució. Pot minvar la qualitat de vida del pacient i propiciar l’absentisme laboral, i constitueix un gran repte per als professionals sanitaris. L'objectiu d'aquest document és oferir al professional un coneixement actualitzat sobre les millors actuacions preventives i curatives en el maneig i tractament de les úlceres d’extremitat inferior. També facilitar informació sobre mesures diagnòstiques i terapèutiques per a cada situació clínica, per poder millorar la qualitat i eficiència de les cures proporcionades des d'una perspectiva holística i individualitzada

Contemporary use of cefazolin for MSSA infective endocarditis: analysis of a national prospective cohort

Objectives: This study aimed to assess the real use of cefazolin for methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis (IE) in the Spanish National Endocarditis Database (GAMES) and to compare it with antistaphylococcal penicillin (ASP). Methods: Prospective cohort study with retrospective analysis of a cohort of MSSA IE treated with cloxacillin and/or cefazolin. Outcomes assessed were relapse; intra-hospital, overall, and endocarditis-related mortality; and adverse events. Risk of renal toxicity with each treatment was evaluated separately. Results: We included 631 IE episodes caused by MSSA treated with cloxacillin and/or cefazolin. Antibiotic treatment was cloxacillin, cefazolin, or both in 537 (85%), 57 (9%), and 37 (6%) episodes, respectively. Patients treated with cefazolin had significantly higher rates of comorbidities (median Charlson Index 7, P <0.01) and previous renal failure (57.9%, P <0.01). Patients treated with cloxacillin presented higher rates of septic shock (25%, P = 0.033) and new-onset or worsening renal failure (47.3%, P = 0.024) with significantly higher rates of in-hospital mortality (38.5%, P = 0.017). One-year IE-related mortality and rate of relapses were similar between treatment groups. None of the treatments were identified as risk or protective factors. Conclusion: Our results suggest that cefazolin is a valuable option for the treatment of MSSA IE, without differences in 1-year mortality or relapses compared with cloxacillin, and might be considered equally effective