Actividad y eficacia experimental de fármacos antifúngicos frente a levaduras causantes de micosis sistémicas

Tot i que les teràpies per les infeccions fúngiques han millorat molt en els últims 10 anys, les infeccions per fongs oportunistes segueixen sent una greu amenaça, especialment pels pacients inmunocompromesos. La baixa incidéncia d’aquestes infeccions ha dificultat l’adopció d’estratègies terapeútiques eficaces pel que, estàn associades a una elevada mortalitat. L’objectiu d’aquesta tesi ha estat contribuir al desenvolupament d’alternatives terapeútiques experimentals per les micosis oportunistes causades pels patògens emergents Saprochaete capitata, Cryptococcus albidus, Cryptococcus laurentii, Rhodotorula mucilaginosa i Saccharomyces cerevisiae. Avaluacions in vitro i in vivo es van portar a terme i han permès proposar noves alternatives terapeútiques per les infeccions causades per aquests patògens.Aunque las terapias para las infecciones fúngicas han mejorado mucho en los últimos 10 años, las infecciones por hongos oportunistas siguen siendo una grave amenaza, especialmente para los pacientes inmunocomprometidos. La baja incidencia de estas infecciones ha dificultado la adopción de estrategias terapéuticas eficaces por lo que, están asociadas a una elevada mortalidad El objetivo de esta tesis ha sido contribuir al desarrollo de alternativas terapéuticas experimentales para las micosis oportunistas causadas por los patógenos emergentes Saprochaete capitata, Cryptococcus albidus, Cryptococcus laurentii, Rhodotorula mucilaginosa y Saccharomyces cerevisiae. Evaluaciones in vitro e in vivo se llevaron a cabo y han permitido proponer nuevas alternativas terapéuticas para las infecciones causadas por estos patógenos.Although therapies for fungal infections have improved much during last 10 years, infections by opportunistic fungus still are a serious threat, especially for immune-compromised patients. The low influence of these infections have complicated the adoption of effective therapeutic strategies, hence they’re associated with a high mortality rate. The goal of this thesis has been to contribute the development of experimental therapies alternative for opportunistic mycoses originated by emerging pathogens Saprochaete capitata, Cryptococcus albidus, Cryptococcus laurentii, Rhodotorula mucilaginosa and Saccharomyces cerevisiae. In vitro and in vivo evaluations were carried out and they have led us to propose new therapeutic alternatives for the infections caused by these pathogens

Colonización por dermatofitos en conejos mantenidos en tiendas de mascotas de Santiago de Chile

Objective: The dermatophytes are keratinophilic fungi, of importance in public health because of their anthropozoophilic nature. Given the increasing acquisition of exotic animals as pets and the scarce studies on the state of colonization by dermatophytes on these animals; we raised the objective of determine the presence of dermatophytes in clinically healthy rabbits (Oryctolagus cuniculus) from pet stores in Santiago, Chile. Materials and Methods: 42 clinically healthy rabbits were studied. Clinical specimens were obtained from the hairy mantle and cultivated on Sabouraud glucose agar and dermatophyte test medium (DTM™); the identification of the fungal isolates was performed using classic mycological procedures that included direct microscopic examination and the analysis of micromorphological features on culture. Results: of the total number of rabbits studied, three (7.1%) presented colonization by dermatophytes, being more frequent in males and in those animals that coexisted with Guinea Pigs. The species identified in all three cases was Trichophyton mentagrophytes. Conclusions: This study evidence colonization by dermatophytes in domestic rabbits, important information for veterinarians and owners of pets, at the time of being in contact with this animal species.Objetivo: Los dermatofitos son hongos queratinofílicos, de importancia en salud pública por su rol antropozoofílico. Dado el aumento en la adquisición de animales exóticos como mascotas y los escasos estudios sobre el estado de colonización por dermatofitos en estos animales, nos planteamos el objetivo de determinar la presencia de dermatofitos en conejos (Oryctolagus cuniculus) clínicamente sanos procedentes de tiendas de mascotas en Santiago de Chile. Materiales y Métodos: Se estudiaron 42 conejos clínicamente sanos fueron estudiados. Las muestras clínicas se obtuvieron fueron obtenidas desde el manto piloso y cultivadas en agar Sabouraud glucosado y dermatophyte test medium (DTM®). La identificación del agente aislado fue realizada por procedimientos micológicos clásicos que incluyeron examen microscópico directo y cultivo. Resultados: Del total de conejos estudiados, tres (7,1%) presentaron colonización por dermatofitos, siendo más frecuente en machos y en aquellos animales que convivían con cuyes. La especie identificada en los tres casos fue Trichophyton mentagrophytes. Conclusiones: Este estudio evidencia la colonización por dermatofitos en conejos domésticos, información importante para médicos veterinarios y propietarios de mascotas, al momento de estar en contacto con esta especie animal.

Successful Completion of the JWST OGSE2 Cryogenic Test at JSC Chamber-A While Managing Numerous Challenges

The James Webb Space Telescope (JWST) Optical Telescope Element (OTE) assembly is the largest optically stable infrared-optimized telescope currently being manufactured and assembled, and scheduled for launch in 2018. The JWST OTE, including the primary mirrors, secondary mirror, and the Aft Optics Subsystems (AOS) are designed to be passively cooled and operate at near 45 degrees Kelvin. Due to the size of its large sunshield in relation to existing test facilities, JWST cannot be optically or thermally tested as a complete observatory-level system at flight temperatures. As a result, the telescope portion along with its instrument complement will be tested as a single unit very late in the program, and on the program schedule critical path. To mitigate schedule risks, a set of 'pathfinder' cryogenic tests will be performed to reduce program risks by demonstrating the optical testing capabilities of the facility, characterizing telescope thermal performance, and allowing project personnel to learn valuable testing lessons off-line. This paper describes the 'pathfinder' cryogenic test program, focusing on the recently completed second test in the series called the Optical Ground Support Equipment 2 (OGSE2) test. The JWST OGSE2 was successfully completed within the allocated project schedule while faced with numerous conflicting thermal requirements during cool-down to the final cryogenic operational temperatures, and during warm-up after the cryo-stable optical tests. The challenges include developing a pre-test cool-down and warm-up profiles without a reliable method to predict the thermal behaviors in a rarified helium environment, and managing the test article hardware safety driven by the project Limits and Constraints (L&C's). Furthermore, OGSE2 test included the time critical Aft Optics Subsystem (AOS), a part of the flight Optical Telescope Element that would need to be placed back in the overall telescope assembly integrations. The OGSE2 test requirements included the strict adherence of the project contamination controls due to the presence of the contamination sensitive flight optical elements. The test operations required close coordination of numerous personnel while they being exposed and trained for the 'final' combined OTE and instrument cryo-test in 2017. This paper will also encompass the OGSE2 thermal data look-back review

Dermatofitosis en gatos domésticos (Felis catus) positivos a retrovirus

The aim of this study was to isolate dermatophyte fungi from dermal lesions present in domestic cats (Felis catus) positive to immunodeficiency virus (FIV) and feline leukemia virus (FelLeF) retrovirals. Thirty-five felines were studied: 9 positives to FIV, 24 to VLeF and 2 to both viruses, patients of the veterinary clinic of the Santo Tomás University of Santiago de Chile. Hair and skin scale samples were obtained from skin lesions suspected of dermatophytosis, which were analyzed by direct microscopic examination and culture to identify mycotic agents. Results showed that 68.6% of the cats were diagnosed with dermatophytosis, Microsporum canis being the main isolated agent. The results indicate a significant association between the presence of dermatophytosis and the immunological compromise of the patients.El objetivo de este estudio fue aislar hongos dermatofitos desde lesiones dérmicas presentes en gatos domésticos (Felis catus) positivos a los retrovirus virus de la inmunodeficiencia felina (VIF) y virus de la leucemia felina (VLeF). Fueron estudiados 35 felinos: 9 positivos a VIF, 24 a VLeF y 2 a ambos virus, atendidos en la clínica veterinaria de la Universidad Santo Tomás de Santiago de Chile. Las muestras de pelos y escamas fueron obtenidas desde las lesiones dérmicas sospechosas de dermatofitosis, las cuales fueron analizadas mediante examen microscópico directo y cultivo para identificar a los agentes micóticos. El 68.6% de los felinos fueron diagnosticados con dermatofitosis, siendo Microsporum canis el principal agente aislado. Los resultados indican una asociación significativa entre la presencia de dermatofitosis y el compromiso inmunológico de los pacientes

Detección de Helicobacter spp en la mucosa gástrica de felinos domésticos clínicamente sanos mediante la prueba rápida de ureasa e histopatología

The aim of this study was to detect Helicobacter spp through the rapid urease test and histopathology in clinically healthy domestic felines (Felis silvestris catus) and to establish the degree of concordance between both methods. Fifteen cats without clinical signs of gastrointestinal disease, between 2 and 7 years old, without distinction of breed and sex, without dietary changes and without having undergone antibiotic or proton pump inhibitor therapy in the last 90 days were included. Endoscopy was performed to macroscopically evaluate the gastric mucosa and obtain biopsies of the gastric fundus and body. It was determined, with both tests, that 86.6% of the samples were positive for the presence of Helicobacter spp, finding 100% concordance between the two tests. In 40% (6/15) of the felines macroscopic lesions were observed in the gastric mucosa, but no association was found between the lesions with the presence of Helicobacter spp. It is concluded that 86.6% of the felines presented colonization by Helicobacter spp, and that the rapid urease test constitutes a reliable method for the diagnosis of infection by Helicobacter spp.El objetivo del estudio fue detectar Helicobacter spp a través de la prueba rápida de ureasa e histopatología en felinos domésticos (Felis silvestris catus) clínicamente sanos y establecer el grado de concordancia entre ambos métodos. Se incluyeron 15 gatos sin signos clínicos de enfermedad gastrointestinal, entre 2 y 7 años, sin distinción de raza y sexo, sin cambios dietarios y sin haber sido sometidos a terapias con antibióticos o inhibidores de la bomba de protones en los últimos 90 días. Se realizó la endoscopia para evaluar macroscópicamente la mucosa gástrica y obtener biopsias del fondo y cuerpo gástrico. Se determinó, con ambas pruebas, que 86.6% de las muestras fueron positivas a la presencia de Helicobacter spp, encontrándose 100% de concordancia entre las dos pruebas. En el 40% (6/15) de los felinos se observaron lesiones macroscópicas en mucosa gástrica, pero no se encontró asociación entre las lesiones con la presencia de Helicobacter spp. Se concluye que 86.6% de los felinos presentaron colonización por Helicobacter spp, y que la prueba rápida de ureasa constituye un método confiable para el diagnóstico de infección por Helicobacter spp

Integration of prevention and control measures for female genital schistosomiasis, HIV and cervical cancer

Female genital schistosomiasis as a result of chronic infection with Schistosoma haematobium (commonly known as bilharzia) continues to be largely ignored by national and global health policy-makers. International attention for large-scale action against the disease focuses on whether it is a risk factor for the transmission of human immunodeficiency virus (HIV). Yet female genital schistosomiasis itself is linked to pain, bleeding and sub- or infertility, leading to social stigma, and is a common issue for women in schistosomiasis-endemic areas in sub-Saharan Africa. The disease should therefore be recognized as another component of a comprehensive health and human rights agenda for women and girls in Africa, alongside HIV and cervical cancer. Each of these three diseases has a targeted and proven preventive intervention: antiretroviral therapy and pre-exposure prophylaxis for HIV; human papilloma virus vaccine for cervical cancer; and praziquantel treatment for female genital schistosomiasis. We discuss how female genital schistosomiasis control can be integrated with HIV and cervical cancer care. Such a programme will be part of a broader framework of sexual and reproductive health and rights, women’s empowerment and social justice in Africa. Integrated approaches that join up multiple public health programmes have the potential to expand or create opportunities to reach more girls and women throughout their life course. We outline a pragmatic operational research agenda that has the potential to optimize joint implementation of a package of measures responding to the specific needs of girls and wome