Radiative corrections to the polarizability tensor of an electrically small anisotropic dielectric particle

Radiative corrections to the polarizability tensor of isotropic particles are fundamental to understand the energy balance between absorption and scattering processes. Equivalent radiative corrections for anisotropic particles are not well known. Assuming that the polarization within the particle is uniform, we derived a closed-form expression for the polarizability tensor which includes radiative corrections. In the absence of absorption, this expression of the polarizability tensor is consistent with the optical theorem. An analogous result for infinitely long cylinders was also derived. Magneto optical Kerr effects in non-absorbing nanoparticles with magneto-optical activity arise as a consequence of radiative corrections to the electrostatic polarizability tensor.This work has been supported by the EU NMP3-SL-2008-214107-Nanomagma, the Spanish MICINN Consolider NanoLight (CSD2007-00046), FIS2006-11170-C02-02 and by the Comunidad de Madrid Microseres-CM Program. R.G.-M. acknowledges support from the EU COST-MP0803. Work by R.G.-M. and L.S.F.-P. was supported by the MICINN “Juan de la Cierva” Program.Peer reviewe

Microbiological, histological, immunological, and toxin response to antibiotic treatment in the mouse model of Mycobacterium ulcerans disease.

Mycobacterium ulcerans infection causes a neglected tropical disease known as Buruli ulcer that is now found in poor rural areas of West Africa in numbers that sometimes exceed those reported for another significant mycobacterial disease, leprosy, caused by M. leprae. Unique among mycobacterial diseases, M. ulcerans produces a plasmid-encoded toxin called mycolactone (ML), which is the principal virulence factor and destroys fat cells in subcutaneous tissue. Disease is typically first manifested by the appearance of a nodule that eventually ulcerates and the lesions may continue to spread over limbs or occasionally the trunk. The current standard treatment is 8 weeks of daily rifampin and injections of streptomycin (RS). The treatment kills bacilli and wounds gradually heal. Whether RS treatment actually stops mycolactone production before killing bacilli has been suggested by histopathological analyses of patient lesions. Using a mouse footpad model of M. ulcerans infection where the time of infection and development of lesions can be followed in a controlled manner before and after antibiotic treatment, we have evaluated the progress of infection by assessing bacterial numbers, mycolactone production, the immune response, and lesion histopathology at regular intervals after infection and after antibiotic therapy. We found that RS treatment rapidly reduced gross lesions, bacterial numbers, and ML production as assessed by cytotoxicity assays and mass spectrometric analysis. Histopathological analysis revealed that RS treatment maintained the association of the bacilli with (or within) host cells where they were destroyed whereas lack of treatment resulted in extracellular infection, destruction of host cells, and ultimately lesion ulceration. We propose that RS treatment promotes healing in the host by blocking mycolactone production, which favors the survival of host cells, and by killing M. ulcerans bacilli

Evaluación de la respuesta serológica contra IBR a partir de la utilización de vacunas polivalentes disponibles en el mercado.

La Rinotraqueítis infecciosa bovina (IBR) es una enfermedad de distribución mundial que provoca grandes pérdidas económicas en nuestro país y el mundo. En la provincia de La Pampa se ha reportado su presencia y amplia distribución territorial. En general la prevención de IBR ha estado centrada en la utilización de vacunas polivalentes. El objetivo del presente trabajo fue evaluar la respuesta serológica a través de los niveles de anticuerpos presentes. Para ello se utilizaron 3 vacunas comerciales polivalentes que contenían en su formulación Herpesvirus bovino tipo 1 (BVH1) inactivado. Se utilizaron 4 grupos de terneros. G1 estuvo integrado por 14 animales, G2 y G3 por 13 animales y G4 o control (-) por 9 animales. Los animales fueron vacunados en dos oportunidades con un intervalo de 21 días. Para la detección de anticuerpos se utilizó un kit de ELISA. Al finalizar el ensayo al día 42 el porcentaje de animales que presentaron anticuerpos vacunales contra IBR fue del 42,8%, 61,5% y 38,4% para los grupos G1, G2 y G3 respectivamente y de 0% para los animales de G4 o grupo control (-). Las medias geométricas del IRPC (Índice Relativo x 100) en la misma fecha fueron de 16,31; 27,7 y 15,12 para los grupos G1, G2 y G3 respectivamente. Las vacunas utilizadas desarrollaron anticuerpos contra IBR en todos los grupos inoculados existiendo diferencias en el porcentaje de animales positivos de cada grupo. Los niveles de anticuerpos generados por las diferentes vacunas no presentaron diferencias significativas entre sí. Por último, se encontraron diferencias significativas entre el nivel de anticuerpos generado por las vacunas y los niveles obtenidos por pasaje viral

Magnetic Resonance-Based Attenuation Correction and Scatter Correction in Neurological Positron Emission Tomography/Magnetic Resonance Imaging—Current Status With Emerging Applications

In this review, we will summarize the past and current state-of-the-art developments in attenuation and scatter correction approaches for hybrid positron emission tomography (PET) and magnetic resonance (MR) imaging. The current status of the methodological advances for producing accurate attenuation and scatter corrections on PET/MR systems are described, in addition to emerging clinical and research applications. Future prospects and potential applications that benefit from accurate data corrections to improve the quantitative accuracy and clinical applicability of PET/MR are also discussed. Novel clinical and research applications where improved attenuation and scatter correction methods are beneficial are highlighted

Detection of Mycolactone A/B in Mycobacterium ulcerans–Infected Human Tissue

Skin infection with bacteria called Mycobacterium ulcerans causes Buruli ulcer, a disease common in West Africa and mainly affecting children. M. ulcerans is the only mycobacterium to cause disease by production of a toxin. This lipid molecule called mycolactone diffuses from the site of infection, killing surrounding cells and, at low concentration, suppressing the immune response. The aim of this study was to show that mycolactone can be detected among lipids extracted from human M. ulcerans lesions in order to study its role in the pathogenesis of M. ulcerans disease. Lipids were extracted from skin biopsies and tested for the presence of mycolactone using thin layer chromatography and mass spectrometry. The extracts were shown to kill cultured cells in a cytotoxicity assay. Mycolactone was detected in both pre-ulcerative and ulcerative forms of the disease and also in lesions during antibiotic treatment but with reduced bioactivity, suggesting a lower concentration compared to untreated lesions. These findings indicate that there is mycolactone in affected skin at all stages of M. ulcerans disease and it could be used as a biomarker for monitoring the clinical response to antibiotic treatment

Cellular Immunity Confers Transient Protection in Experimental Buruli Ulcer following BCG or Mycolactone-Negative Mycobacterium ulcerans Vaccination

BACKGROUND: Buruli ulcer (BU) is an emerging infectious disease caused by Mycobacterium ulcerans that can result in extensive necrotizing cutaneous lesions due to the cytotoxic exotoxin mycolactone. There is no specific vaccine against BU but reports show some degree of cross-reactive protection conferred by M. bovis BCG immunization. Alternatively, an M. ulcerans-specific immunization could be a better preventive strategy. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we used the mouse model to characterize the histological and cytokine profiles triggered by vaccination with either BCG or mycolactone-negative M. ulcerans, followed by footpad infection with virulent M. ulcerans. We observed that BCG vaccination significantly delayed the onset of M. ulcerans growth and footpad swelling through the induction of an earlier and sustained IFN-gamma T cell response in the draining lymph node (DLN). BCG vaccination also resulted in cell-mediated immunity (CMI) in M. ulcerans-infected footpads, given the predominance of a chronic mononuclear infiltrate positive for iNOS, as well as increased and sustained levels of IFN-gamma and TNF. No significant IL-4, IL-17 or IL-10 responses were detected in the footpad or the DLN, in either infected or vaccinated mice. Despite this protective Th1 response, BCG vaccination did not avoid the later progression of M. ulcerans infection, regardless of challenge dose. Immunization with mycolactone-deficient M. ulcerans also significantly delayed the progression of footpad infection, swelling and ulceration, but ultimately M. ulcerans pathogenic mechanisms prevailed. CONCLUSIONS/SIGNIFICANCE: The delay in the emergence of pathology observed in vaccinated mice emphasizes the relevance of protective Th1 recall responses against M. ulcerans. In future studies it will be important to determine how the transient CMI induced by vaccination is compromised

Corticosteroid-Induced Immunosuppression ultimately does not compromise the efficacy of antibiotherapy in murine mycobacterium ulcerans Infection

Buruli ulcer (BU) is a necrotizing disease of the skin, subcutaneous tissue and bone caused by Mycobacterium ulcerans. It has been suggested that the immune response developed during the recommended rifampicin/streptomycin (RS) antibiotherapy is protective, contributing to bacterial clearance. On the other hand, paradoxical reactions have been described during or after antibiotherapy, characterized by pathological inflammatory responses. This exacerbated inflammation could be circumvented by immunosuppressive drugs. Therefore, it is important to clarify if the immune system contributes to bacterial clearance during RS antibiotherapy and if immunosuppression hampers the efficacy of the antibiotic regimen. METHODOLOGY/PRINCIPAL FINDINGS: We used the M. ulcerans infection footpad mouse model. Corticosteroid-induced immunosuppression was achieved before experimental infection and maintained during combined RS antibiotherapy by the administration of dexamethasone (DEX). Time-lapsed analyses of macroscopic lesions, bacterial burdens, histology and immunohistochemistry were performed in M. ulcerans-infected footpads. We show here that corticosteroid-immunosuppressed mice are more susceptible to M. ulcerans, with higher bacterial burdens and earlier ulceration. Despite this, macroscopic lesions remised during combined antibiotic/DEX treatment and no viable bacteria were detected in the footpads after RS administration. This was observed despite a delayed kinetics in bacterial clearance, associated with a local reduction of T cell and neutrophil numbers, when compared with immunocompetent RS-treated mice. In addition, no relapse was observed following an additional 3 month period of DEX administration. CONCLUSIONS/SIGNIFICANCE: These findings reveal a major role of the RS bactericidal activity for the resolution of M. ulcerans experimental infections even during immunosuppression, and support clinical investigation on the potential use of corticosteroids or other immunosuppressive/anti-inflammatory drugs for the management of BU patients undergoing paradoxical reactions.This work was supported by a grant from the Health Services of Fundação Calouste Gulbenkian, and the Portuguese Science and Technology Foundation (FCT) fellowships SFRH/BD/41598/2007, SFRH/BPD/64032/2009, SFRH/BPD/68547/2010 and SFRH/BD/33573/2009 to TGM, GT, AGF, and JBG, respectively. MS is a Ciência 2007 fello