RESUMEN
Candida spp. are one of the most common fungal pathogens. Biofilms formed by Candidaalbicans 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 Colección Española 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.
RESUMEN
A family of heterofunctional Schiff base carbosilane metallodendrons with [Ru(η5-C5H5)(PTA)Cl] (PTA = 1,3,5-triaza-7-phosphatricyclo-[3.3.1.1]decane) at the focal point and dimethylamino groups on the periphery are described. The new systems have proved their ability to interact with biological molecules such as Human Serum Albumin (HSA) without affecting its secondary structure and erythrocytes membranes, causing haemolysis in a dose and generation dependent way. The combination of two active functional groups in one single dendritic platform has shown a cooperative effect in the viability of HeLa and PC-3 cells, with the second generation derivative standing out as the most promising with the lowest IC50. Experiments focused on advanced prostate cancer have shown an antimetastasic activity for those metallodendrons, hindering the adhesion of cells in one of the main targets of metastasis, bones, and inhibiting cell migration. Finally, the second generation metallodendron with one single metal centre and four dimethylamino groups on the dendritic wedge, was selected for an ex vivo experiment in nude mice with advanced prostate cancer inhibiting the tumour growth in a 40% compared to control mice.
Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Neoplasias de la Próstata/tratamiento farmacológico , Rutenio/química , Rutenio/farmacología , Silanos/química , Silanos/farmacología , Animales , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Dendrímeros/química , Dendrímeros/farmacología , Dendrímeros/uso terapéutico , Células HeLa , Humanos , Masculino , Ratones , Ratones Desnudos , Compuestos Organometálicos/química , Compuestos Organometálicos/farmacología , Compuestos Organometálicos/uso terapéutico , Células PC-3 , Neoplasias de la Próstata/patología , Rutenio/uso terapéutico , Silanos/uso terapéuticoRESUMEN
Antimicrobial proteins, like lysozymes produced by animals or bacteriophage lysins, enable the degradation of bacterial peptidoglycan (PG) and, consequently, lead to bacterial cell lysis. However, the activity of those enzymes is not satisfactory against gram-negative bacteria because of the presence of an outer membrane (OM) barrier. Lytic enzymes can therefore be combined with membrane-disrupting agents, such as dendritic silver nanoparticles. Nevertheless, a lipopolysaccharide (LPS), especially the smooth type, could be the main hindrance for highly charged nanoparticles to get direct access to the bacterial OM and to help lytic enzymes to reach their target PG. Herein, we have investigated the interactions of PEGylated carbosilane dendritic nanoparticles with P. aeruginosa 010 LPS in the presence of lysozymes and KP27 endolysin to find out the main aspects of the OM destabilization process. Our results showed that PEGylated dendronized AgNPs overcame the LPS barrier and enhanced the antibacterial effect of endolysin more efficiently than unPEGylated nanoparticles.
RESUMEN
Fibromatosis is the most frequent benign uterine pathology of fertile women, rarely causing anomalous enlargement of the uterus. Traditionally the surgical treatment has been abdominal hysterectomy. However, development of minimally invasive techniques has led to major safeness of the laparoscopic route. We report a case of total laparoscopic hysterectomy performed on a uterus weighting more than 3,000 g and present a review of the literature about the laparoscopic approach to very enlarged uteri.
RESUMEN
Se realizó una encuesta a algunos estomatólogos de la provincia de Villa Clara para comprobar el tratamiento prescrito a los pacientes que asisten a consulta por procesos inflamatorios sépticos, los cuales, casi en su totalidad indicaban un antininflamatorio, sin tener en cuenta que la inflamación es una reacción de defensa del organismos donde los tejidos reaccionan con mayor actividad, produciendo en una fase una serie de cambios que tienden a anular y a eliminar las causas que los irrita. Tales cambios son: hiperemia, leucocitosis, polimorfonucleosis, exudación, diapédesis y fagocitosis, lo que trae como consecuencia que se inhiba esta reacción
Asunto(s)
Proceso Alveolar , Celulitis (Flemón)/terapia , Pulpitis/terapiaRESUMEN
Se realizó una encuesta a algunos estomatólogos de la provincia de Villa Clara para comprobar el tratamiento prescrito a los pacientes que asisten a consulta por procesos inflamatorios sépticos, los cuales, casi en su totalidad indicaban un antininflamatorio, sin tener en cuenta que la inflamación es una reacción de defensa del organismos donde los tejidos reaccionan con mayor actividad, produciendo en una fase una serie de cambios que tienden a anular y a eliminar las causas que los irrita. Tales cambios son: hiperemia, leucocitosis, polimorfonucleosis, exudación, diapédesis y fagocitosis, lo que trae como consecuencia que se inhiba esta reacción