A promising camptothecin derivative: Semisynthesis, antitumor activity and intestinal permeability

Oral administration of camptothecin (Cm) derivatives and other antitumoral agents is being actively developed in order to improve the quality of life of patients with cancer. Though several lipophilic derivatives of CPT have shown interesting oral bioavailability in preclinical and clinical studies, only Topotecan has been approved for this route of administration. Semisynthesis, antitumor activity, biological inhibition mechanism, and in situ intestinal permeability of 9, 10-[1,3]-Dioxinocamptothecin (CDiox), an unexplored CPT derivative, have been studied in this paper. The hexacyclic analog was as effective as Topotecan and CPT in different tumor cell lines, showing an expected similar apoptosis cell mechanism and high ability to inhibit DNA synthesis in HeLa, Caco-2, A375 and MDA-MB-231 cell lines. Furthermore, in vitro and in situ pharmacokinetics transport values obtained for CDiox displayed more favorable absorption profile than CPT and Topotecan. (C) 2014 Elsevier Masson SAS. All rights reserved.G.R.-B. acknowledges Instituto de Tecnologia Quimica for a scholarship; Consolider-Ingenio 2010 (proyecto MULTICAT), Sub-programa de Apoyo a Centros de Excelencia Severo Ochoa, and Agencia de Gestico, d'Ajuts Universiteris i de Recerca (2009 SGR 758, to S.S.) I.G.-A., V.M.-S., M.G.-A. and M. B. acknowledge financial support from the European Financial Commission (Red bioFarma DCI-ALA/19.09.01/10/21526/245-297/ALFA III (2010)). J.L.G.-G. acknowledges the financial support of the CIBERER (Biomedical Network Research Center for Rare Diseases) ISCIII.Rodríguez Berna, G.; Mangas Sanjuan, V.; Gonzalez Alvarez, M.; Gonzalez Álvarez, I.; Garcia Gimenez, JL.; Díaz Cabañas, MJ.; Bermejo, M.... (2014). A promising camptothecin derivative: Semisynthesis, antitumor activity and intestinal permeability. European Journal of Medicinal Chemistry. 83:366-373. doi:10.1016/j.ejmech.2014.06.050S3663738

Role of age and comorbidities in mortality of patients with infective endocarditis

[Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

ZIF-8 and Its Magnetic Functionalization as Vehicle for the Transport and Release of Ciprofloxacin

The use of nanomaterials for the controlled release of drugs aims to enhance their effectiveness, especially when poorly soluble in water, and achieve their rapid, localized, and effective administration. The present study focuses on the use of a Zeolitic Imidazolate Framework-8 (ZIF-8) as vehicle for the transport and controlled release of the antibiotic ciprofloxacin (CIP) as model due to its favorable physicochemical characteristics. The objective is to synthesize the ZIF-8 material loaded with CIP through encapsulation for subsequent release of the drug in neutral and acid physiological media. In addition, functionalization of the CIP/ZIF compound with magnetic nanoparticles (NP) was sought to increase its traceability through the possible use of magnetic fields. Characterizations by XRD, FT-IR, SEM-EDX, and TGA showed a satisfactory synthesis of both pure ZIF-8 and ciprofloxacin-loaded ZIF-8, with high crystallinity and thermal stability. The release profiles showed an abrupt initial release that stabilized over time. A much higher release (20–80% greater) was obtained in acid versus neutral pH in all cases, attributable to the collapse of the ZIF-8 structure in acid media. In addition, functionalization of the material with iron NPs did not affect the behavior of the system during drug release. Antimicrobial activity tests against E. coli and S. aureus showed that ZIF-8 per se exerts antimicrobial activity, while the compounds CIP/ZIF and magnetic CIP/ZIF increased the antimicrobial capacity of pure CIP by 10–20%. The ZIF-8 system has high potential as a drug carrier and release agent for the treatment of diseases, especially those that cause acidification of the cellular environment, achieving a rapid, localized, and targeted action with the possibility of achieving traceability of the system after its magnetic functionalization.P18-RT-419

Anales de Edafología y Agrobiología Tomo 38 Número 5-6

Suelos. Estudio genético del suelo tipo del Alto de los Leones (Madrid) por A. Hoyos de Castro, Mª L. Palomar G. Villamil y J. Hernando Costa.-- Desarrollo del suelo sobre material silícico en función del tiempo, clima y vegetación, por A. Hoyos de Castro, Mª L. Palomar, Gª. Villamil y C. Fernández Bermejo.-- Estqdio de materiales caoliníticos de Sierra Morena occidental. I. Propiedades y proceso de génesis de caolines de Cerro Colora (Riotinto, Huelva), por J. Poyata Ferrera, F. González García, G. García Ramos y J. L. Pérez Rodríguez.-- Estudio de materiales caoliníticos de Sierra Morena occidental. II. Propiedades y proceso de génesis de caolines de Traslasierra (Huelva), por J. Poyato Ferrera. F. González García, J. L. Pérez Rodríguez y G. García Ramos.-- Estudio edáfico del sector Jabalcuz-Los Villares. IV. Mineralogía de la fracción arcilla, por C. Dorronsoro. J. Aguilar y C. Antolín.-- Estudio del Cambisol «Los Labrados» sobre granito de El Pedroso (Sevilla). I. Datos del medio, morfología y propiedades generales, por L. Corral Mora, N. Bellinjante Crocci, M. Medina Carnicer y G. Paneque Guerrero.-- Meteorización de sedimentos carbonatados blandos bajo clima mediterráneo, por Juan L. de Olmedo Pujol.-- Contenido en fósforo total y su relación con otros parámetros en una cronosecuencia de Andepts de las Islas Canarias, por E. Fernández Caldas, J. A. Pérez Méndez, F. Gutiérrez Jerez y A. Borges Pérez .-- Influencia del pH en la génesis de gibsita-clorit.a-vermiculita y caolinita en suelos de Navarra, por Elisa Barragán Landa y Jaime Iñíguez Herrero.-- Evaluación para riegos de los suelos de la Estación Experimental La Mayora, por Juan de Olmedo Pujol y Roque Romero Díaz.-- Cambios sinecológicos de la microflora telúrica asociados a las repoblaciones forestales con especies exóticas, por F. Velasco de Pedro y J. M. Lozano Calle.-- Propiedades físicas y químicas en relación con la porosidad de los suelos: Influencia del ciclo natural de humectación-desecación. II. Porosidad total y diferencial, por J. L. Arrúe Ugarte y J. Martín Aranda.-- Propiedades físicas y químicas en relación con la porosidad de los suelos : Influencia del ciclo natural de humectación-desecación. III. Porosidad y fracción arcilla, por J: L. Arrúe Ugarte, F. Moreno, J. L. Pérez Rodríguez y J. Martín Aranda.-- Influjo del ion Mg++ en la evolución del ortofosfato dicálcico dihidrato en contacto con suspensiones de minerales de la arcilla, por J. García de Leániz, F. González García y J. A. Pinilla Barrau.—Fertilidad de Suelos. Ahijamiento y producción del trigo de primavera. II. Respuesta al calcio y manganeso e interacciones de los nutrientes, por V. J. Mangas Martín y L. Sanchez de la Puente.-- Respuesta de la asociación trigo-avena loca a la fertilización potásica, por R. González Ponce.-- Respuesta de la asociación trigo-avena loca a la fertilización nitrogenada, por R. González Ponce.-- Efectos del tamaño de grano de fertilizantes PK en la producción de praderas, por R. Fábregas, E. Vieitez y J. Ariñes.--Aplicación de los espectros de diversidad al estudio de la heterogeneidad en comunidades de pastizal, por A. Puerto Martín, A. Escudero Berián y J. M. Gómez Gtrrez.-- Correlaciones entre bioelementos en especies pratenses bajo los efectos de la madurez. II. Gramíneas, por A. Valdés Amado, B. García Criado y J. M. Gómez Gutiérrez.-- Estudio comparativo de métodos para la determinación de fósforo orgánico total en andosoles, por F. Gutiérrez Jeres, E. Fernández Caldas, J. A. Pérez Méndez e l. Trujillo Jacinto del Castillo.—Nutrición y Fisiología Vegetal.-- Efectos fisiológicos de la interacción boro-manganeso en plantas de tomate. II. Absorción y distribución de macroelementos, por M. C. Alvarez-Tinaut, A. Leal, l. Agüi y L. Recalde.-- Efectos fisiológicos de la interacción boro-manganeso en plantas de tomate. III. Absorción y distribución de los microelementos Mn, Cu y Zn, por M. C. Alvarez.-Tinaut, A. Leal, M. Gómez y. L. Recalde.-- Relaciones fisiológicas de bioelementos durante el crecimiento y desarrollo de la hoja y el brote de limoneros cultivados en suelos salinos, por A. H ernansáez, M.a Parra y A. Ortuño.-- Los macronutrientes catiónicos en el maíz (Zea mays L.). I. Variaciones de la composición con el desarrollo, por Benito Sánchez y Gerardo Dios.-- Los macronutrientes catiónicos en el maíz (Zea mays L.). II. Evolución de la acumulación de K. Ca y Mg, y de sus relaciones durante el cultivo, por Benito Sánchez y Gerardo Dios.-- Empleo de unidades térmicas y capa negra en la clasificación de híbridos de maíz para Galicia, por A. Ordás.-- Evolución de los equilibrios fisiológicos y sus relaciones con el metabolismo de macro y micronutrientes en cultivos de olivar, por C Mazuelos Vela, J. Prieto Alcántara J. Liñán Benjunzea y E. Esteban Velasco.-- Influencia de compuestos fenólicos sobre la destrucción auxínica, por M. C. Mato.-- Notas.Peer reviewed2019-08.- CopyBook.- Libnova.- Biblioteca IC

Role of age and comorbidities in mortality of patients with infective endocarditis.

The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups: A total of 3120 patients with IE (1327  There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in th

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