Study of antifungal agent caspofungin adsorption to laboratory materials

[EN] Treatment of invasive fungal infections with Caspofungin is used as the first-line antifungal agents. The minimum inhibitory concentration value is a test which indicates the degree of sensitivity of a strain regarding a drug. However, no value of minimum inhibitory concentration for caspofungin is available because very variable value is obtained. In this work, we study the link with the adsorption phenomenon of CSF previously described in literature and the lack of minimum inhibitory concentration value. A systematic study of the impact of different parameters on CSF adsorption is reported. The effect of the nature of container material, the aqueous solution pH and the organic solvent proportion was studied. In addition, the possibility of using a coating agent to minimize the adsorption was assayed and evaluated. Results obtained showed the importance of the material used during the manipulation of CSF. The use of acidic pH aqueous solution or the addition of acetonitrile or methanol proportions (50 % and 70 %, respectively) were found efficient to avoid adsorption of CSF on glassware material, which is the relevant strategy for analytical samples of caspofungin. The treatment of HPLC glass vials and 96-well plates with N-(2-aminoethyl)-3-aminopropyltrimethoxysilane reduced the adsorption. The significant adsorption observed in this work especially with plastic materials, questions the results obtained before in different assays and explained the absence of MIC value.The authors thank University of the Basque Country (UPV/EHU) (Project GIU19/068 and Project COLAB20/11) and Basque Government (grant number IT1362-19) for financial support. B. Uribe thanks UPV/EHU for the pre-doctoral fellowship in co-supervision with the University of Bordeaux. X. Guruceaga thanks the Basque Government for his predoctoral grant

Kaspofungina ekinokandinaren in vitro azterlanen ikuspegi analitikoa

226 p.It is known that invasive fungal infections have become a concern around the world due to the morbidity and mortality shown. The main responsible of these infections are aspergillus, cryptococcus and candida genus. However, candida has gained the attention of specialists due to the mortality shown in some population groups, where it can arrived to 40 %. Invasive candidiasis is treated with four antifungal drug families: azoles, polyenes, pirimidine analogues and echinocandins. Because of their use, fungi have developed different resistance mechanisms to ensure their proliferation even in presence of the drugs.As resistance mechanisms to echinocandin family remain, low specialists use them as a first-line therapy for invasive candidiasis. Unfortunately, in the last decade resistance of C. glabrata species to echinocandins has risen, especially to caspofungin (CSF).In this context, this work presents a deep sight of how to work with CSF in in vitro studies. First, an analytical methodology for the quantification of CSF in RPMI-1640 cell culture media has been developed and validated successfully. Secondly, the attempt of studying C. glabrata¿s resistance to CSF has been done, by means of two compartment pharmacokinetic/pharmacodynamic in vitro model. Finally, a stability study of CSF has been carried out checking degradation and adsorption possibilities. Results obtained shown the difficulties of working with CSF in human body conditions (pH around 7 and in aqueous solution) due to the adsorption phenomenon. This research provides a new perspective to assess the results obtained previously in microbiological and therapeutic fields and, supports researchers to go deeper in the evaluation of the reliability of the methodologies used for resistance determination and drug administration

Kaspofungina ekinokandinaren in vitro azterlanen ikuspegi analitikoa

226 p.It is known that invasive fungal infections have become a concern around the world due to the morbidity and mortality shown. The main responsible of these infections are aspergillus, cryptococcus and candida genus. However, candida has gained the attention of specialists due to the mortality shown in some population groups, where it can arrived to 40 %. Invasive candidiasis is treated with four antifungal drug families: azoles, polyenes, pirimidine analogues and echinocandins. Because of their use, fungi have developed different resistance mechanisms to ensure their proliferation even in presence of the drugs.As resistance mechanisms to echinocandin family remain, low specialists use them as a first-line therapy for invasive candidiasis. Unfortunately, in the last decade resistance of C. glabrata species to echinocandins has risen, especially to caspofungin (CSF).In this context, this work presents a deep sight of how to work with CSF in in vitro studies. First, an analytical methodology for the quantification of CSF in RPMI-1640 cell culture media has been developed and validated successfully. Secondly, the attempt of studying C. glabrata¿s resistance to CSF has been done, by means of two compartment pharmacokinetic/pharmacodynamic in vitro model. Finally, a stability study of CSF has been carried out checking degradation and adsorption possibilities. Results obtained shown the difficulties of working with CSF in human body conditions (pH around 7 and in aqueous solution) due to the adsorption phenomenon. This research provides a new perspective to assess the results obtained previously in microbiological and therapeutic fields and, supports researchers to go deeper in the evaluation of the reliability of the methodologies used for resistance determination and drug administration

Odol Tanta Lehorraren fidagarritasunaren azterketa farmakoen analisi kuantitatiborako UHPLC-PDA-FLDren bidez

Lan honetan Odol Tanta Lehorraren (OTLa) laginketa-teknikaren fidagarritasuna ikertu da farmakoen analisirako fotodiodo- eta fluoreszentzia-detektagailuei akoplatutako bereizmen oso altuko likido-kromatografiaren (UHPLC-PDA-FLD) bidez. OTLak, odol-tanta bat kotoi-paperezko euskarri batean jartzean eta lehortzen uztean datzan teknikak, azken urteotan erabileraren handipen garrantzitsua antzeman du bioanalisian. OTLak ohiko odol-analisiekiko hainbat abantaila erakutsi arren, analisi kuantitatiboaren ikuspuntutik hainbat faktorerekiko mendekotasuna duela antzeman da. Ikerketa honetan faktore batzuek (hematokritoa, odol-bolumena eta laginketa-puntua) farmakoen determinazioan duten eragina aztertu da, horretarako amilorida, propranolola eta valsartan farmakoak eredu gisa erabiliz. Emaitzetan oinarrituta, zuloaren kokapenak eta hematokritoak analisien zehaztasunean eta doitasunean eragina dutela ondorioztatu da, teknika honen aplikazio kuantitatiboa mugatuz. Bestalde, analitoen sakabanaketa odol-tantan zehar analitoen propietate fisiko-kimikoen mendekoa dela ikusi da, metodo analitikoaren garapenean analito bakoitzaren sakabanaketa aztertu behar dela ondorioztatuz.; In this work, the reliability of Dried Blood Spot (DBS) as a sampling technique for drug analysis was studied by Ultra High Performance Liquid Chromatography coupled to Photodiode-Array and Fluorescence Detection (UHPLC-PDA-FLD). DBS microsampling, a technique based on placing a drop of blood in a cotton support that is allowed to air dry, has lately noticed an increase in use in bioanalysis.Even though it offers several advantages compared to common blood sampling methods, it also shows some limitations for quantitative analysis due to the dependence on different factors. In this study, the influence of some of them (hematocrit, blood volume and sampling position) has been investigated, using amiloride, propranolol and valsartan drugs as model compounds. According to the results, it has been concluded that the sampling position and the hematocrit have influence in the accuracy and precision of the quantitative results, therefore limiting the use of this technique for quantitative analysis. On the other hand, dispersion of the analytes in the blood drop depends on their physicochemical properties which implies that the distribution of each analyte must be carefully studied during method development

Informe del taller de 2012 de la Sociedad Latinoamericana de Espondiloartritis para la Educación y la Investigación en Inmunología y Medicina

3 páginasThe first annual meeting of the Latin American Spondyloarthritis Society for Education and Research in Immunology and Medicine (LASSERIM) was held in Bogotá, Colombia, in September 2012 and was attended by key opinion leaders, researchers, and rheumatologists. The meeting included presentations and discussions from renowned speakers during 2 days and a coaching leadership exercise led by an expert in the field followed by an open forum. Two groups defined a priori discussed the establishment of a professional network and organization to be involved in the identification, assessment, and effective resolution of health care issues in Latin America. A broad spectrum of topics were discussed but focused on the following: pharmacoeconomics in general rheumatology, spondyloarthritis and chronic back pain, therapeutic interventions in rheumatoid arthritis, ultrasonography in spondyloarthritis, impact of social media in medicine and global trends in leadership, quality of life, and innovation. A special workshop on coaching in health care and coaching as a tool to implement LASSERIM goals was part of the 2-day conference. LASSERIM will be working in the future on education, research, and innovation in the field of rheumatology and immunology. A special focus will be on spondyloarthritis, by promoting research, open discussions, and by conducting carefully planned research studies to impact on the quality of life of patients and doctors from Latin American countries.La primera reunión anual de la Sociedad Latinoamericana de Espondiloartritis para la Educación e Investigación en Inmunología y Medicina (LASSERIM) se celebró en Bogotá, Colombia, en septiembre de 2012 y contó con la presencia de líderes de opinión, investigadores y reumatólogos clave. La reunión incluyó presentaciones y debates de renombrados oradores durante 2 días y un ejercicio de liderazgo de coaching dirigido por un experto en el campo seguido de un foro abierto. Dos grupos definidos a priori discutieron el establecimiento de una red y organización profesional que participe en la identificación, evaluación y resolución efectiva de problemas de atención de salud en América Latina. Se discutió un amplio espectro de temas pero se centró en los siguientes: farmacoeconomía en reumatología general, espondiloartritis y dolor de espalda crónico, intervenciones terapéuticas en artritis reumatoide, ecografía en espondiloartritis, impacto de las redes sociales en medicina y tendencias globales en liderazgo, calidad de vida, e innovación. Como parte de la conferencia de dos días, se celebró un taller especial sobre coaching en el cuidado de la salud y coaching como herramienta para implementar los objetivos de LASSERIM. LASSERIM trabajará en el futuro en educación, investigación e innovación en el campo de la reumatología y la inmunología. Se prestará especial atención a la espondiloartritis, promoviendo la investigación, los debates abiertos y realizando estudios de investigación cuidadosamente planificados para impactar la calidad de vida de los pacientes y médicos de los países latinoamericanos

Divulgación Científica No.4

En las instituciones encargadas de adelantar proyectos de investigación, como es el caso de la universidad, debemos reflexionar sobre lo que hacemos y sus implicaciones, de tal forma que encontremos claves para propiciar, desde nuestros saberes, agentes dinamizadores que animen la discusión, el debate y la comparación. Lo anterior con el enfoque de proponer caminos y soluciones para problemas actuales que nos aquejan como individuos. Las distintas búsquedas que hacemos apuntan a contribuir a la construcción de mejores sociedades, y la investigación es una valiosa herramienta con a que contamos para lograrlo. Es necesario entender la investigación como un agente que permite y propicia cambios.In the institutions in charge of carrying out research projects, such as the university, we must reflect on what we do and its implications, in such a way that we find keys to promote, from our knowledge, dynamic agents that encourage discussion, debate and the comparison. The above with the focus of proposing paths and solutions for current problems that afflict us as individuals. The different searches that we do aim to contribute to the construction of better societies, and research is a valuable tool that we have to achieve it. It is necessary to understand research as an agent that allows and promotes changes