Prediction of Antileishmanial Compounds: General Model, Preparation, and Evaluation of 2‑Acylpyrrole Derivatives

In this work, the SOFT.PTML tool has been used to pre-process a ChEMBL dataset of pre-clinical assays of antileishmanial compound candidates. A comparative study of different ML algorithms, such as logistic regression (LOGR), support vector machine (SVM), and random forests (RF), has shown that the IFPTML-LOGR model presents excellent values of specificity and sensitivity (81−98%) in training and validation series. The use of this software has been illustrated with a practical case study focused on a series of 28 derivatives of 2-acylpyrroles 5a,b, obtained through a Pd(II)-catalyzed C−H radical acylation of pyrroles. Their in vitro leishmanicidal activity against visceral (L. donovani) and cutaneous (L. amazonensis) leishmaniasis was evaluated finding that compounds 5bc (IC50 = 30.87 μM, SI > 10.17) and 5bd (IC50 = 16.87 μM, SI > 10.67) were approximately 6-fold more selective than the drug of reference (miltefosine) in in vitro assays against L. amazonensis promastigotes. In addition, most of the compounds showed low cytotoxicity, CC50 > 100 μg/ mL in J774 cells. Interestingly, the IFPMTL-LOGR model predicts correctly the relative biological activity of these series of acylpyrroles. A computational high-throughput screening (cHTS) study of 2-acylpyrroles 5a,b has been performed calculating >20,700 activity scores vs a large space of 647 assays involving multiple Leishmania species, cell lines, and potential target proteins. Overall, the study demonstrates that the SOFT.PTML all-in-one strategy is useful to obtain IFPTML models in a friendly interface making the work easier and faster than before. The present work also points to 2-acylpyrroles as new lead compounds worthy of further optimization as antileishmanial hits.Ministerio de Ciencia e Innovación (PID2019-104148GB-I00), Gobierno Vasco (IT1558-22

Molecular Characterization of Cryptosporidium spp. in Cultivated and Wild Marine Fishes from Western Mediterranean with the First Detection of Zoonotic Cryptosporidium ubiquitum

Altres ajuts: Ministerio para la transición ecológica y el reto demográfico 2019/1476 i 2020/792Cryptosporidium is a widespread pathogen that infects a broad range of vertebrates, including humans, in which it is one of the main causes of diarrhea worldwide. Marine fishes also harbor Cryptosporidium species, including zoonotic ones. The goal of this study is to evaluate the presence of Cryptosporidium species in edible marine fishes using molecular tools. The area of study, located in the Western Mediterranean, is an important area for marine fish production and capture. The following three groups were studied: cultivated fish, wild fish that aggregate in the surroundings of marine fish farms and wild fish from extractive fisheries. Results show that the most affected group is the group of wild fish from the vicinity of fish farms. Two species were mainly identified, C. molnari (fish specific) and zoonotic C. ubiquitum. The presence of zoonotic C. ubiquitum in two European sea bass (Dicentrarchus labrax) highlights a potential risk for fish consumers. Fish not only harbor host-specific species/genotypes of Cryptosporidium, but also species like zoonotic C. parvum or anthroponotic C. hominis, which can pose a risk for fish consumers. This study aims to investigate fish cryptosporidiosis in an important aquaculture and fishery area of the Western Mediterranean (Comunidad Valenciana, Spain). We analyzed 404 specimens belonging to the following three groups: cultivated fish (N = 147), wild synanthropic fish (N = 147) and wild fish from extractive fisheries (N = 110). Nested PCR targeting the 18S rRNA gene, followed by sequencing and phylogenetic analysis, were performed. Positive isolates were also amplified at the actin gene locus. An overall prevalence of 4.2% was detected, with the highest prevalence in the synanthropic group (6.1%). C. molnari was identified in thirteen specimens from seven different host species. Zoonotic C. ubiquitum was detected in two European sea bass (Dicentrarchus labrax). One isolate similar to C. scophthalmi was detected in a cultivated meagre (Argyrosomus regius), and one isolate, highly divergent from all the Cryptosporidium species/genotypes described, was identified from a synanthropic round sardinella (Sardinella aurita). This study contributes to increasing the molecular data on fish cryptosporidiosis, expanding the range of known hosts for C. molnari and identifying, for the first time, zoonotic C. ubiquitum in edible marine fishes, pointing out a potential health risk

Amphotericin B ocular films for fungal keratitis and a novel 3D printed microfluidic ocular lens infection model

Fungal keratitis (FK), a severe eye infection that leads to vision impairment and blindness, poses a high risk to contact lens users, and Candida albicans remains the most common underpinning fungal pathogen in temperate climates. Patients are initially treated empirically (econazole 1% drops hourly for 24–48 h), and if there is no response, amphotericin B (AmB) 0.15% eye drops (extemporaneously manufactured to be stable for a week) are the gold-standard treatment. Here, we aim to develop a sustained-release AmB ocular film to treat FK with an enhanced corneal retention time. As there is a paucity of reliable in vitro models to evaluate ocular drug release and antifungal efficacy under flow, we developed a 3D-printed microfluidic device based on four chambers stacked in parallel, in which lenses previously inoculated with a C. albicans suspension were placed. Under the flow of a physiological fluid over 24 h, the release from the AmB-loaded film that was placed dry onto the surface of the wetted contact lenses was quantified, and their antifungal activity was assessed. AmB sodium deoxycholate micelle (dimeric form) was mixed with sodium alginate and hyaluronic acid (3:1 w/w) and cast into films (0.48 or 2.4%), which showed sustained release over 24 h and resulted in a 1.23-fold reduction and a 5.7-fold reduction in CFU/mL of C. albicans, respectively. This study demonstrates that the sustained delivery of dimeric AmB can be used for the treatment of FK and provides a facile in vitro microfluidic model for the development and testing of ophthalmic antimicrobial therapies

The effect of an anti-inflammatory diet on chronic pain: a pilot study

ObjectiveRheumatic diseases result in chronic pain (CP) and require treatment with drugs whose prolonged administration is associated with side effects. However, publications in the academic literature have suggested that diet modification and food supplementation can play a crucial role in alleviating the symptoms of inflammatory disease. Thus, it is hoped that the use of an anti-inflammatory diet for pain management might result in improved quality of life. Hence, here we aimed to investigate the effect of anti-inflammatory foods in patients with CP caused by rheumatic diseases.MethodsAfter an exhaustive bibliography search, we designed a 13-item anti-inflammatory dietary guide based on a Mediterranean diet without red meat, gluten, or cow’s milk (the AnMeD-S). We then conducted a pilot study to evaluate the efficacy of this anti-inflammatory diet in patients with CP. A food consumption score (with a maximum of 156 points) was then applied to evaluate patient adhesion to the proposed diet. Forty-five patients with CP were followed-up for 4 months. Variables related with quality of life (including pain perception, depression status, and sleep satisfaction) were measured using 9 validated questionnaires and anthropometric measurements were recorded before and after the participants followed the anti-inflammatory diet.ResultsWe found a correlation between increased anti-inflammatory food intake and improved physical characteristics, stress, and pain in the patients we assessed. Moreover, decreased consumption of pro-inflammatory foods was positively correlated with sleep satisfaction. Following the AnMeD-S was associated with improved physical characteristics and quality-of-life in patients with CP.ConclusionThe AnMeD-S, includes anti-inflammatory foods and restricts the consumption of certain pro-inflammatory foods (such as those containing gluten). This dietary pattern could provide relief from CP and improve the symptoms of stress and depression, as well as reducing sleep disturbances

Targeting lung macrophages for fungal and parasitic pulmonary infections with innovative amphotericin B dry powder inhalers

The incidence of fungal pulmonary infections is known to be on the increase, and yet there is an alarming gap in terms of marketed antifungal therapies that are available for pulmonary administration. Amphotericin B (AmB) is a highly efficient broad-spectrum antifungal only marketed as an intravenous formulation. Based on the lack of effective antifungal and antiparasitic pulmonary treatments, the aim of this study was to develop a carbohydrate-based AmB dry powder inhaler (DPI) formulation, prepared by spray drying. Amorphous AmB microparticles were developed by combining 39.7% AmB with 39.7% γ-cyclodextrin, 8.1% mannose and 12.5% leucine. An increase in the mannose concentration from 8.1 to 29.8%, led to partial drug crystallisation. Both formulations showed good in vitro lung deposition characteristics (80% FPF< 5 µm and MMAD < 3 µm) at different air flow rates (60 and 30 L/min) when used with a DPI, but also during nebulisation upon reconstitution in water

Aprender a emprender entre los estudiantes universitarios de posgrado

Depto. de Farmacia Galénica y Tecnología AlimentariaFac. de FarmaciaFALSEsubmitte

Experiencia docente en el nuevo sistema de evaluación continua en la asignatura de Parasitología en la titulación de Farmacia

La asignatura de Parasitología en la titulación de Farmacia tiene como objeto que el alumno, como futuro profesional sanitario, sea capaz de asesorar adecuadamente en el tratamiento y control de las enfermedades parasitarias así como de diagnosticarlas y de preparar métodos diagnósticos adecuados. En el proceso de adaptación al EEES, la Universidad Cardenal-Herrera CEU ha empezado a aplicar un Sistema de Evaluación Continua (EC), en el cual se pretende valorar tanto los conocimientos (mediante exámenes tradicionales) como las habilidades y/o destrezas adquiridas durante el curso (trabajos, exposiciones, prácticas de laboratorio, participación activa en clase). La Parasitología se imparte en el segundo cuatrimestre de 2º curso, la dureza de la materia y la poca utilidad que el alumno percibe de ella en su futuro laboral, obliga al docente universitario en esta asignatura a modificar las estrategias en cuanto a la forma de impartirla y de captar “el interés” de sus alumnos. Por otro lado, el sistema de Evaluación Continua se aplica en todas las asignaturas, lo que supone un esfuerzo considerable para los alumnos, y es necesario por tanto aumentar su motivación y demostrarle que el sobre-esfuerzo que está realizando se refleje en su nota final. En el presente trabajo se pretende exponer la experiencia del profesor de esta materia en una Universidad privada en la aplicación de este sistema de evaluación así como la valoración que los alumnos hacen del mismoSIN FINANCIACIÓNNo data 200

Caracterización inmunobiológica de las especies quísticas de "trichinella"

Tesis de la Universidad Complutense de Madrid, Facultad de Farmacia, Departamento de Parasitología, leída el 28-05-1999Depto. de Microbiología y ParasitologíaFac. de FarmaciaTRUEpu

Objetivo Bolonia

Desde el curso 2006/07, la Universidad Cardenal Herrera-CEU ha iniciado un proceso de adaptación al EEES en todas sus titulaciones. Las directrices marcadas desde Bolonia buscan potenciar el aprendizaje autónomo, el desarrollo de competencias (y no sólo de contenidos), la evaluación práctica y continuada y la adecuación de los conocimientos a la realidad de la sociedad del siglo XXI. No existen sin embargo “metodologías docentes estándar” que el profesor pueda utilizar para conseguir todos esos objetivos, labor que se complica aún más en el caso de determinadas materias que resultan “poco atractivas para el alumno” como es la Parasitología en la Titulación de Farmacia. Para facilitar el estudio el profesor ha diseñado diversas estrategias para motivar a los alumnos: material didáctico (apuntes, ejercicios, esquemas de autoevaluación), tutoralización y seguimiento de los conocimientos impartidos, evaluación, presentación de trabajos experimentales en el congreso de estudiantes, simulación de atención farmacéutica en el aula de Oficina de Farmacia, etc. En el presente trabajo se pretende exponer la experiencia personal del profesor y la valoración que han hecho los alumnos mediante una encuesta sobre la metodología aplicada.SIN FINANCIACIÓNNo data 200