N-aryltetrahydroisoquinoline derivatives as HA-CD44 interaction inhibitors: Design, synthesis, computational studies, and antitumor effect

Hyaluronic acid (HA) plays a crucial role in tumor growth and invasion through its interaction with cluster of differentiation 44 (CD44), a non-kinase transmembrane glycoprotein, among other hyaladherins. CD44 expression is elevated in many solid tumors, and its interaction with HA is associated with cancer and angiogenesis. Despite efforts to inhibit HA-CD44 interaction, there has been limited progress in the development of small molecule inhibitors. As a contribution to this endeavour, we designed and synthesized a series of N-aryltetrahydroisoquinoline derivatives based on existing crystallographic data available for CD44 and HA. Hit 2e was identified within these structures for its antiproliferative effect against two CD44+ cancer cell lines, and two new analogs (5 and 6) were then synthesized and evaluated as CD44-HA inhibitors by applying computational and cell-based CD44 binding studies. Compound 2-(3,4,5-trimethoxybenzyl)-1,2,3,4-tetrahydroisoquinolin-5-ol (5) has an EC50 value of 0.59 μM against MDA-MB-231 cells and is effective to disrupt the integrity of cancer spheroids and reduce the viability of MDA-MB-231 cells in a dose-dependent manner. These results suggest lead 5 as a promising candidate for further investigation in cancer treatment

Design and implementation of a mobile app for the pharmacotherapeutic follow-up of patients diagnosed with immune-mediated inflammatory diseases: eMidCare

BackgroundPharmacotherapeutic management of immune-mediated inflammatory diseases (IMID) has become more complex due to the development of new treatments, such as biological therapies. Mobile health, especially apps, can provide IMID patients with greater autonomy and facilitate communication with healthcare professionals. Our objective was to design and implement an app for remote monitoring and communication with IMID patients.MethodsA multidisciplinary group was created to design and develop an app for IMID patients in a tertiary hospital. The app functionalities were identified through a focus group with IMID patients and through an observational, descriptive study of available apps for IMID patients at App Store and Play Store platforms. Once the app was designed and developed, we offered the app to IMID patients who initiated a new biological therapy. The inclusion period was from December 2020 to August 2021. We performed an observational, longitudinal study to assess the app’s impact on medication safety, communication, satisfaction, and usability.ResultsWe designed an app (eMidCare®) with the following modules: My Medication, My Questionnaires, Adverse Events, Useful Information, Messages, and Patient Profile. A total of 85 patients were installed with the app. The median (range) follow-up time for app use was 123 (5-270) days. In the My Medication module, 100% of patients registered their biological therapy and 25.9% also used this module to record each dose of medication administered. A total of 82 adverse events (AEs) were registered. Thirty-two percent of the patients registered at least 1 AE. The most frequent AEs were fatigue, injection site reaction, headache, and nausea. Fifty-two percent of patients used the Messages module to communicate with healthcare professionals. The most frequent messages concerned doubts about managing AEs (26.2%) and drug interactions (18.9%). The satisfaction survey yielded a median (range) score of 9.1 (7-10) out of 10.ConclusionsWe developed an app, eMidCare®, which reminds patients to take their medication, enables them to record AEs, and helps them communicate with healthcare professionals. Approximately one-third of the patients registered the administration of the biological therapies and registered at least 1 AE. The most used and most satisfactory functionality was communication with health professionals

Social wasps in Spain: the who and where.

The objective of this study was to list the social vespids occurring in Spain, determine their presence in each region, and correlate the data with the vespids responsible for allergic reactions and their progression over time. Insects distribution data were collected in two phases: from the southern half of Spain (2008-2012), and from the northern half of Spain (2016-2019). Data for the vespids were collected from the prescriptions of Hymenoptera venom immunotherapy (HVIT) at six Spanish hospitals in the years 2009 and 2019. Polistes dominula and Vespula germanica were the most widely distributed species. Vespa velutina was found to be present in a large part of northern Spain. During the 10 year period, the prescriptions of vespid VIT increased by 42.63%. The north of Spain saw a 3.61 fold greater predominance of prescriptions for Vespula (to some extent influenced by Vespa velutina allergy) whereas in central and southern Spain, there was a 3.97 fold greater predominance of prescriptions for Polistes. It is the first study that compares the vespid distribution maps with VIT prescription. A noteworthy finding is the wide presence of Polistes dominula and Vespula germanica in Spain and the appearance of Vespa velutina allergy in the northern part of the country. Data of HVIT prescriptions reflect inter-regional variability with the predominance of Vespula (due to Vespula and Vespa) in the north and that of Polistes in the center and south of Spain

Allergy to stings and bites from rare or locally important arthropods: Worldwide distribution, available diagnostics and treatment

: Insect venom allergy is the most frequent cause of anaphylaxis in Europe and possibly worldwide. The majority of systemic allergic reactions after insect stings are caused by Hymenoptera, and among these, vespid genera induce most of the systemic sting reactions (SSR). Honey bees are the second leading cause of SSR. Depending on the global region, other Hymenoptera such as different ant genera are responsible for SSR. Widely distributed hornets and bumblebees or local vespid or bee genera rarely induce SSR. Hematophagous insects such as mosquitoes and horse flies usually cause (large) local reactions while SSR occasionally occur. This position paper aimed to identify either rare or locally important insects causing SSR as well as rarely occurring SSR after stings or bites of widely distributed insects. We summarized relevant venom or saliva allergens and intended to identify possible cross-reactivities between the insect allergens. Moreover, we aimed to locate diagnostic tests for research and routine diagnosis, which are sometimes only regionally available. Finally, we gathered information on available immunotherapies. Major allergens of most insects were identified, and cross-reactivity between insects was frequently observed. While some diagnostics and immunotherapies are locally available, standardized skin tests and immunotherapies are generally lacking in rare insect allergy

Search for modulators of VEGF-KDR interaction: Hydrocarbon-bridged VEGF derived peptides

Trabajo presentado en el 30th European Peptide Symposium, celebrado en Helsinki (Finlandia) del 31 de agosto al 05 de septiembre de 2008

Frequency of clonal mast cell diseases among patients presenting with anaphylaxis: A prospective study in 178 patients from 5 tertiary centers in Spain

This work was supported by grants from the Fundación Sociedad Española Alergología e Inmunología Clínica (SEAIC) 2014

Anchuelo. Propuestas bioclimáticas en el espacio público

Anchuelo. Propuestas bioclimáticas en el espacio público. Publicación digital de los trabajos elaborados por los estudiantes del curso 2021/22 de la asignatura La Ciudad y el Medio de la Escuela Técnica Superior de Arquitectura de Madrid de la Universidad Politécnica de Madrid. Muestra una serie de propuestas elaboradas en la asignatura para mejorar bioclimáticamente diferentes espacios públicos municipales en el marco del acuerdo realizado entre el Departamento de Urbanística y Ordenación del Territorio y el Excmo. Ayuntamiento de Anchuelo (Madrid)