Bases moleculares de la resistencia a daptomicina en staphylococcus aureus

[ES]Daptomicina es una de las alternativas antimicrobianas disponibles en la actualidad para tratar infecciones causadas por patógenos Gram positivos multiresistentes, incluyendo SARM y VISA. Aunque el aislamiento de cepas no sensibles al antimicrobiano es infrecuente, se han propuesto varios mecanismos para explicar dicho fenómeno. En esta memoria se desarrolló y ejecutó un método de selección in vitro de cepas con alto nivel de resistencia a daptomicina, donde se seleccionaron 12 mutantes a partir de 9 aislados clínicos previamente insensibles a daptomicina. Tanto los aislados clínicos utilizados en este estudio como los mutantes obtenidos in vitro, se estudiaron genéticamente y se determinó que los principales genes involucrados en la resistencia a daptomicina son mprF, la familia rpo, cls1, cls2, y podría estar también relacionado el gen mw1109. Asimismo, se evaluó la capacidad de supervivencia en presencia y ausencia de competidor, además de la capacidad formadora de biofilm, la cual apenas se vio afectada, a diferencia del fitness que fue en general pésimo. Finalmente, se llevó acabo un estudio de los componentes de lípidos y ácidos grasos que conforman la pared bacteriana, que reafirmó la estrecha relación de los cambios en ella con la insensibilidad a daptomicina

Acute pancreatitis-associated pancreatic panniculitis

A 52-year-old male with a past history of acute pancreatitis four years before, and now he entered with a 30-day disease duration with painful violaceous tumors on the lower limbs. The skin biopsy study was compatible with pancreatic panniculitis. During hospitalization the patient had a new episode of mild pancreatitis with positive response to the standard treatment, with resolution of the skin lesions.Varón de 52 años con antecedente de pancreatitis aguda cuatro años antes de su ingreso; acudió con tiempo de enfermedad de 30 días caracterizado por tumoraciones dolorosas de color violáceo en miembros inferiores. La biopsia de piel mostró signos compatibles con paniculitis pancreática. Durante su hospitalización el paciente cursó con un nuevo cuadro de pancreatitis aguda con respuesta favorable a tratamiento de soporte con lo que las lesiones en miembros inferiores evolucionaron favorablemente

Essential hypertension: which antihypertensive agent to choose?

Introduction: Systemic arterial hypertension (HT) constitutes the main risk factor for cardiovascular morbidityand mortality at a global level, affecting all ages regardless of gender and ethnicity. Its treatment continues to be a challenge, given the persistence of poor control, especially in countries like Colombia. Objective: To showthe available evidence regarding the updated treatments of HT and the correct choice of antihypertensive agents according to the individual needs of each patient. Likewise, to consolidate and compare the hypotensive effect of the most used antihypertensive agents. Methodology: An advanced search was carried out with the terms DeCS and MeSH: Hypertension, antihypertensive agents, Essential Hypertension and Combination Therapy through the search engines PubMed, Clinical Key, Lilacs, Scielo. A total of 109 articles were selected to prepare the present literature review. Conclusions: An individualized hypertension treatment plan leads to the recognition of the different phenotypes, the presence of complications, the gender, and race, which are fundamental aspects to consider when choosing the appropriate antihypertensive agents. These findings allow for the achievement of the desiredblood pressure target and leads to reduction and prevention of complications derived from suboptimal control.Introducción: la hipertensión arterial sistémica (HTA) constituye el principal factor de riesgo para morbilidad y mortalidad cardiovascular a nivel global, afecta a todas las edades, sin distinción de género y etnicidad. Su tratamiento continúa constituyendo un reto, dada la persistencia del pobre control, especialmente en países como Colombia. Objetivo: mostrar la evidencia disponible respecto al tratamiento actualizado de la HTA y la elección certera delos agentes antihipertensivos acorde con la individualidad de cada paciente. Asimismo, consolidar y comparar el efecto hipotensor de cada agente antihipertensivo más usado. Metodología: se realizó una búsqueda avanzada con los términos DeCS y MeSH: hipertensión, agentes antihipertensivos, hipertensión esencial y terapia combinada,en los motores de búsqueda PubMed, Clinical Key, Lilacs, Scielo. Un total de 109 artículos se seleccionaron paraelaborar en la presente revisión de la literatura. Conclusiones: la individualización del manejo de la HTA lleva al reconocimiento de los distintos fenotipos, la presencia de complicaciones, el examen físico, el género y la raza como puntos fundamentales para elegir el agente antihipertensivo más adecuado que permita alcanzar las metas de control y propenda por la reducción y prevención de las complicaciones derivadas de un control no óptimo.Introducción: la hipertensión arterial sistémica (HTA) constituye el principal factor de riesgo para morbilidad y mortalidad cardiovascular a nivel global, afecta a todas las edades, sin distinción de género y etnicidad. Su tratamiento continúa constituyendo un reto, dada la persistencia del pobre control, especialmente en países como Colombia. Objetivo: mostrar la evidencia disponible respecto al tratamiento actualizado de la HTA y la elección certera delos agentes antihipertensivos acorde con la individualidad de cada paciente. Asimismo, consolidar y comparar el efecto hipotensor de cada agente antihipertensivo más usado. Metodología: se realizó una búsqueda avanzada con los términos DeCS y MeSH: hipertensión, agentes antihipertensivos, hipertensión esencial y terapia combinada,en los motores de búsqueda PubMed, Clinical Key, Lilacs, Scielo. Un total de 109 artículos se seleccionaron paraelaborar en la presente revisión de la literatura. Conclusiones: la individualización del manejo de la HTA lleva al reconocimiento de los distintos fenotipos, la presencia de complicaciones, el examen físico, el género y la raza como puntos fundamentales para elegir el agente antihipertensivo más adecuado que permita alcanzar las metas de control y propenda por la reducción y prevención de las complicaciones derivadas de un control no óptimo

Amoebicidal activity of cationic carbosilane dendrons derived with 4-phenylbutyric acid against Acanthamoeba griffini and Acanthamoeba polyphaga trophozoites and cysts

Amoebae from the genus Acanthamoeba are important pathogens responsible for severe illnesses in humans such as Acanthamoeba keratitis and granulomatous amoebic encephalitis. In the last few decades, AK diagnoses have steadily increased. Most patients suffering from AK were contact lens users and the infection was related to poor hygiene. However, therapy is not yet well established, and treatments may last for several months due to resistance. Moreover, these treatments have been described to generate cytotoxicity. Therefore, there is an urgent need to develop new therapeutic strategies against AK. In this study, the amoebicidal activity of different generation cationic carbosilane dendrons derived with 4-phenylbutyric acid was demonstrated against Acanthamoeba polyphaga and Acanthamoeba griffini trophozoites and cysts. In addition, the combination of chlorhexidine digluconate and the most effective dendron (ArCO(2)G(2)(SNMe3I)(4)) showed an in vitro effect against Acanthamoeba trophozoites and cysts, reducing the minimal trophozoite amoebicidal concentration as well as concentrations with cysticidal activity.Ministerio de Economía y CompetitividadUniversidad de AlcaláComunidad de Madri

Potential anti-adhesion activity of novel carbosilane zwitterionic dendrimers against eukaryotic and prokaryotic pathogenic microorganisms

The development of biofilms on different surfaces continues to be a major public health problem. The antimicrobial resistance and the difficulty of finding drugs capable of combating these established biofilms generates the urgent need to find compounds that prevent cells from settling and establishing of these complex communities of microorganisms. Zwitterionic modification of nanomaterials allows the formation of a hydration layer, and this highly hydrophilic surface provides antifouling properties as well as a good biocompatibility by preventing non-specific interactions. Thus, they are appropriate candidates to prevent microbial adhesion to different surfaces and, in consequence, avoid biofilm formation. For this reason, we have incorporated zwitterionic moieties in multivalent systems, as are carbosilane dendrimers. Characterization of these systems was performed using nuclear magnetic resonance and mass spectrometry. It has been analysed if the new molecules have capacity to inhibit the biofilm formation in Candida albicans, Staphylococcus aureus and Pseudomonas aeruginosa. The results showed that they were more effective against S. aureus, observing a biofilm reduction of 81.5% treating with 32 mg/L of G2SiZWsf dendrimer and by 72.5% using 32 mg/L of the G3SiZWsf dendrimer. Finally, the absence of cytotoxicity was verified by haemolysis and cytotoxicity studies in human cells lines.Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), SpainMinisterio de Economía, Comercio y EmpresaComunidad de Madri

In Vitro Activity of Carbosilane Cationic Dendritic Molecules on Prevention and Treatment of Candida albicans Biofilms

Candida spp. are one of the most common fungal pathogens. Biofilms formed by Candida albicans offer resistance mechanisms against most antifungal agents. Therefore, development of new molecules effective against these microorganisms, alone or in combination with antifungal drugs, is extremely necessary. In the present work, we carried out a screening process of different cationic carbosilane dendritic molecules against C. albicans. In vitro activity against biofilm formation and biofilms was tested in both Coleccion Espanola de Cultivos Tipo (CECT) 1002 and clinical C. albicans strains. Cytotoxicity was studied in human cell lines, and biofilm alterations were observed by scanning electron microscopy (SEM). Antifungal activity of the carbosilane dendritic molecules was assessed by monitoring cell viability using both established and novel cell viability assays. One out of 14 dendritic molecules tested, named BDSQ024, showed the highest activity with a minimum biofilm inhibitory concentration (MBIC) for biofilm formation and a minimum biofilm damaging concentration (MBDC) for existing biofilm of 16-32 and 16 mg/L, respectively. Synergy with amphotericin (AmB) and caspofungin (CSF) at non-cytotoxic concentrations was found. Therefore, dendritic compounds are exciting new antifungals effective at preventing Candida biofilm formation and represent a potential novel therapeutic agent for treatment of C. albicans infection in combination with existing clinical antifungals.Ministerio de Economía, Industria y CompetitividadComunidad de MadridUniversidad de Alcal

Relatoría III jornadas en tecnologías de la información, telecomunicaciones y el ecosistema digital - Relatoría conferencias magistrales

47 página

Conversatorio: “25 años de las Comisiones de Regulación. Su importancia para Colombia, para la creación de mercados de servicios públicos y telecomunicaciones"

27 página

Novel Treatment Approach against <em>Candida</em> spp.: Evaluation of Antifungal and Antibiofilm <em>In Vitro</em> Activity of Dendritic Molecules

Infections caused by the genus Candida are a serious threat, especially in the sanitary field. These pathogens are able to generate biofilms, which is one of the main problems because they are difficult to eradicate and are associated with a high mortality rate. These biofilms provide Candida species with increased resistance to health care drugs and disinfectants. Currently, the resistance to antifungals is increasing gradually and there are few drugs accepted for clinical use capable of combating them, and, unfortunately, these substances are sometimes toxic at the effective doses required. Therefore, finding new molecules capable of preventing the formation of biofilms or eradicating them once generated is of vital importance. In addition, it is essential to know the appropriate techniques to evaluate a new compound, guaranteeing reliable and precise data. Studies with dendritic systems of cationic nature are recently being carried out, presenting interesting and encouraging results as antimicrobials, against cells cancer cells, surface activating agents, and encapsulation of antibiotic, among others. In this chapter, we will focus on its antifungal capacity, especially its antibiofilm activity against Candida spp

Eradication of Candida albicans Biofilm Viability: In Vitro Combination Therapy of Cationic Carbosilane Dendrons Derived from 4-Phenylbutyric Acid with AgNO3 and EDTA

Candida albicans is a human pathogen of significant clinical relevance. This pathogen is resistant to different drugs, and most clinical antifungals are not effective against the prevention and treatment of C. albicans infections. As with other microorganisms, it can produce biofilms that serve as a barrier against antifungal agents and other substances, contributing to infection in humans and environmental tolerance of this microorganism. Thus, resistances and biofilm formation make treatment difficult. In addition, the complete eradication of biofilms in implants, catheters and other medical devices, is challenging and necessary to prevent relapses of candidemia. Therefore, it is a priority to find new molecules or combinations of compounds with anti-Candida biofilm activity. Due to the difficulty of treating and removing biofilms, the aim of this study was to evaluate the in vitro ability of different generation of cationic carbosilane dendrons derived from 4-phenylbutyric acid, ArCO2Gn(SNMe3I)m, to eradicate C. albicans biofilms. Here, we assessed the antifungal activity of the second generation dendron ArCO2G2(SNMe3I)4 against C. albicans cells and established biofilms since it managed to seriously damage the membrane. In addition, the combinations of the second generation dendron with AgNO3 or EDTA eradicated the viability of biofilm cells. Alterations were observed by scanning electron microscopy and cytotoxicity was assessed on HeLa cells. Our data suggest that the dendritic compound ArCO2G2(SNMe3I)4 could represent an alternative to control the infections caused by this pathogen