Incidence of zygomycosis in transplant recipients

AbstractRecently, a remarkable increase in the incidence of zygomycosis has been reported from institutions in the USA and Europe. The use of voriconazole for the treatment of aspergillosis and, less frequently, the use of echinocandins as empirical treatment for invasive fungal infections are thought to be responsible for the increase. In addition, an increased incidence of this infection has been observed in transplant recipients, including both haematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) patients. There are no global surveys on the prevalence or incidence of zygomycosis, but data from individual institutions and countries show that zygomycosis is an emerging infection. The increased incidence of zygomycosis most probably reflects a greater frequency of predisposing factors, such as higher numbers of patients undergoing HSCT and immunosuppressive chemotherapy. In addition, the emergence of rare pathogens as a result of the rise in the use of antifungal therapy against common species can be postulated. Further, the availability of antifungal agents with activity profiles that are more specific for selected fungi increases the necessity of identifying pathogenic fungi; the frequency of Zygomycetes infections may have been underestimated until now because therapeutic decisions did not depend on the precise identification of pathogenic fungi

The influence of lung microbiota on lung carcinogenesis, immunity and immunotherapy

Microbiota have emerged as key modulators of both the carcinogenic process and the immune response against cancer cells, and, thus, it seems to influence the efficacy of immunotherapy. While most studies have focused on analyzing the influence of gut microbiota, its composition substantially differs from that in the lung. Here, we describe how microbial life in the lungs is associated with host immune status in the lungs and, thus, how the identification of the microbial populations in the lower respiratory tract rather than in the gut might be key to understanding the lung carcinogenic process and to predict the efficacy of different treatments. Understanding the influence of lung microbiota on host immunity may identify new therapeutic targets and help to design new immunotherapy approaches to treat lung cancer

Cryptococcus neoformans complex: actividad in vitro de antifúngicos frente a cepas aisladas de pacientes VIH/SIDA

Cryptococcus neoformans complex (Cn) es el agente más frecuente de meningitis en individuos infectados por el virus de la inmunodeficiencia humana (VIH). El 90 % de los pacientes con VIH/SIDA en todo el mundo son infectados por el serotipo A (var. grubii), mientras que el serotipo D (var. neoformans) se reporta principalmente en Europa, y se lo relaciona con menor sensibilidad a los antifúngicos. En Argentina la tasa de mortalidad alcanza un 35 % dentro del mes de diagnosticada la enfermedad y la sobrevida no supera 1-2 años pos diagnóstico. El tratamiento de elección es con anfotericina B (AB) sola o en combinación con 5-Fluorocitosina (5FC) en la fase aguda, seguida de fluconazol (FZ) durante la fase de mantenimiento. No obstante, la respuesta a la terapéutica convencional es errática y la recidiva es frecuente, con un 20-30 % de fallas en el tratamiento, motivos éstos que hacen necesario el conocimiento de la sensibilidad in vitro de Cn frente a distintos antifúngicos. Objetivos: conocer la actividad in vitro de 5 antifúngicos frente a cepas de Cn aisladas de pacientes VIH/SIDA con criptococosis meníngea (CM).Facultad de Ciencias Veterinaria

Cryptococcus neoformans complex: actividad in vitro de antifúngicos frente a cepas aisladas de pacientes VIH/SIDA

Cryptococcus neoformans complex (Cn) es el agente más frecuente de meningitis en individuos infectados por el virus de la inmunodeficiencia humana (VIH). El 90 % de los pacientes con VIH/SIDA en todo el mundo son infectados por el serotipo A (var. grubii), mientras que el serotipo D (var. neoformans) se reporta principalmente en Europa, y se lo relaciona con menor sensibilidad a los antifúngicos. En Argentina la tasa de mortalidad alcanza un 35 % dentro del mes de diagnosticada la enfermedad y la sobrevida no supera 1-2 años pos diagnóstico. El tratamiento de elección es con anfotericina B (AB) sola o en combinación con 5-Fluorocitosina (5FC) en la fase aguda, seguida de fluconazol (FZ) durante la fase de mantenimiento. No obstante, la respuesta a la terapéutica convencional es errática y la recidiva es frecuente, con un 20-30 % de fallas en el tratamiento, motivos éstos que hacen necesario el conocimiento de la sensibilidad in vitro de Cn frente a distintos antifúngicos. Objetivos: conocer la actividad in vitro de 5 antifúngicos frente a cepas de Cn aisladas de pacientes VIH/SIDA con criptococosis meníngea (CM).Facultad de Ciencias Veterinaria

Rhomboid domain containing 2 (RHBDD2): A novel cancer-related gene over-expressed in breast cancer

In the course of breast cancer global gene expression studies, we identified an uncharacterized gene known as RHBDD2 (Rhomboid domain containing 2) to be markedly over-expressed in primary tumors from patients with recurrent disease. In this study, we identified RHBDD2 mRNA and protein expression significantly elevated in breast carcinomas compared with normal breast samples as analyzed by SAGE (n=46) and immunohistochemistry (n=213). Interestingly, specimens displaying RHBDD2 over-expression were predominantly advanced stage III breast carcinomas (p=0.001). Western-blot, RT-PCR and cDNA sequencing analyses allowed us to identify two RHBDD2 alternatively spliced mRNA isoforms expressed in breast cancer cell lines. We further investigated the occurrence and frequency of gene amplification and over-expression affecting RHBDD2 in 131 breast samples. RHBDD2 gene amplification was detected in 21% of 98 invasive breast carcinomas analyzed. However, no RHBDD2 amplification was detected in normal breast tissues (n=17) or breast benign lesions (n=16) (p=0.014). Interestingly, siRNA mediated silencing of RHBDD2 expression results in a decrease of MCF7 breast cancer cells proliferation compared with the corresponding controls (p=0.001). In addition, analysis of publicly available gene expression data showed a strong association between high RHBDD2 expression and decreased overall survival (p=0.0023), relapsefree survival (p= 0.0013), and metastasis-free interval (p=0.006) in patients with primary ERnegative breast carcinomas. In conclusion, our findings suggest that RHBDD2 over-expression behaves as an indicator of poor prognosis and may play a role facilitating breast cancer progression

Changes of energy fluxes in marine animal forests of the anthropocene: Factors shaping the future seascape

Climate change is already transforming the seascapes of our oceans by changing the energy availability and the metabolic rates of the organisms. Among the ecosystem-engineering species that structure the seascape, marine animal forests (MAFs) are the most widespread. These habitats, mainly composed of suspension feeding organisms, provide structural complexity to the sea floor, analogous to terrestrial forests. Because primary and secondary productivity is responding to different impacts, in particular to the rapid ongoing environmental changes driven by climate change, this paper presents some directions about what could happen to different MAFs depending on these fast changes. Climate change could modify the resistance or resilience of MAFs, potentially making them more sensitive to impacts from anthropic activities (i.e. fisheries and coastal management), and vice versa, direct impacts may amplify climate change constraints in MAFs. Such changes will have knock-on effects on the energy budgets of active and passive suspension feeding organisms, as well as on their phenology, larval nutritional condition, and population viability. How the future seascape will be shaped by the new energy fluxes is a crucial question that has to be urgently addressed to mitigate and adapt to the diverse impacts on natural systems

Sensibilidad in vitro de Fusarium solani complex y F. oxysporum complex de origen clínico y ambiental

Introducción: las especies de Fusarium pueden causar infecciones severas en pacientes transplantados o con cáncer de origen sanguíneo. Asimismo, son causa de onicomicosis en pacientes normoinmunes. La biota endógena del ambiente hospitalario es casi siempre la fuente de infección en los pacientes hospitalizados. El tratamiento se basa en el uso de anfotericina B (AB) y voriconazol (VZ), no obstante, la respuesta suele no ser eficaz y el desenlace fatal es cada vez más frecuente, no solo por la resistencia de Fusarium spp., a los antifúngicos, sino también por las limitadas opciones terapéuticas. Si bien la terbinafina (TB) y el itraconazol (IZ) son de elección para el tratamiento de las dermatoficias muestran potente actividad in vitro frente a un amplio espectro de hongos miceliales. En ciertas infecciones bacterianas y virales se recomienda la asociación de antimicrobianos para optimizar el manejo terapéutico, sin embargo, no existe aún suficiente experiencia ni evidencia con las infecciones fúngicas. La actual disponibilidad de nuevos antifúngicos, y la posibilidad de realizar distintas combinaciones, hacen necesario el conocimiento de la sensibilidad in vitro de Fusarium spp, independientemente del origen del aislado.Facultad de Ciencias Veterinaria

Sensibilidad in vitro de Fusarium solani complex y F. oxysporum complex de origen clínico y ambiental

Introducción: las especies de Fusarium pueden causar infecciones severas en pacientes transplantados o con cáncer de origen sanguíneo. Asimismo, son causa de onicomicosis en pacientes normoinmunes. La biota endógena del ambiente hospitalario es casi siempre la fuente de infección en los pacientes hospitalizados. El tratamiento se basa en el uso de anfotericina B (AB) y voriconazol (VZ), no obstante, la respuesta suele no ser eficaz y el desenlace fatal es cada vez más frecuente, no solo por la resistencia de Fusarium spp., a los antifúngicos, sino también por las limitadas opciones terapéuticas. Si bien la terbinafina (TB) y el itraconazol (IZ) son de elección para el tratamiento de las dermatoficias muestran potente actividad in vitro frente a un amplio espectro de hongos miceliales. En ciertas infecciones bacterianas y virales se recomienda la asociación de antimicrobianos para optimizar el manejo terapéutico, sin embargo, no existe aún suficiente experiencia ni evidencia con las infecciones fúngicas. La actual disponibilidad de nuevos antifúngicos, y la posibilidad de realizar distintas combinaciones, hacen necesario el conocimiento de la sensibilidad in vitro de Fusarium spp, independientemente del origen del aislado.Facultad de Ciencias Veterinaria

Early astrocytic atrophy in the entorhinal cortex of a triple transgenic animal model of Alzheimer's disease

The EC (entorhinal cortex) is fundamental for cognitive and mnesic functions. Thus damage to this area appears as a key element in the progression of AD (Alzheimer's disease), resulting in memory deficits arising from neuronal and synaptic alterations as well as glial malfunction. In this paper, we have performed an in-depth analysis of astroglial morphology in the EC by measuring the surface and volume of the GFAP (glial fibrillary acidic protein) profiles in a triple transgenic mouse model of AD [3xTg-AD (triple transgenic mice of AD)]. We found significant reduction in both the surface and volume of GFAP-labelled profiles in 3xTg-AD animals from very early ages (1 month) when compared with non-Tg (non-transgenic) controls (48 and 54%, reduction respectively), which was sustained for up to 12 months (33 and 45% reduction respectively). The appearance of Aβ (amyloid β-peptide) depositions at 12 months of age did not trigger astroglial hypertrophy; nor did it result in the close association of astrocytes with senile plaques. Our results suggest that the AD progressive cognitive deterioration can be associated with an early reduction of astrocytic arborization and shrinkage of the astroglial domain, which may affect synaptic connectivity within the EC and between the EC and other brain regions. In addition, the EC seems to be particularly vulnerable to AD pathology because of the absence of evident astrogliosis in response to Aβ accumulation. Thus we can consider that targeting astroglial atrophy may represent a therapeutic strategy which might slow down the progression of AD