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Conjunctival vaccination against Brucella ovis in mice with mannosylated nanoparticles

Sat, 31 Dec 2011 23:00:00 GMT

Title: Conjunctival vaccination against Brucella ovis in mice with mannosylated nanoparticles Author(s) : Costa-Martins, R. (Raquel) da; Gamazo, C. (Carlos); Sanchez-Martinez, M. (María); Barberan, M. (Montserrat); Peñuelas, I. (Iván); Irache, J.M. (Juan Manuel) Abstract: The use of sub-unit vaccines can solve some drawbacks associated with traditional attenuated or inactivated ones. However, in order to improve their immunogenicity, these vaccines needs to be associated to an appropriate adjuvant which, adequately selected, may also offer an alternative pathway for administration. The aim of this work was to evaluate the protection offered by the hot saline complex extracted from Brucella ovis (HS) encapsulated in mannosylated nanoparticles (MAN-NP-HS) when instilled conjunctivally in mice. Nanoparticles displayed a size of 300 nm and the antigen loading was close to 30 μg per mg nanoparticle. Importantly, encapsulated HS maintained its protein profile, structural integrity and antigenicity during and after the preparative process of nanoparticles. The ocular immunization was performed on BALB/c mice. Eight weeks after vaccination animals were challenged with B. ovis, and 3 weeks later, were slaughtered for bacteriological examinations. Animals immunized with MAN-NP-HS displayed a 3-log reduction in spleen CFU compared with unvaccinated animals. This degree of protection was significantly higher than that observed for the commercial vaccine (Rev1) subcutaneously administered. Interestingly, the mucosal IgA response induced by MAN-NP-HS was found to be much more intense than that offered by Rev1 and prolonged in time. Furthermore, the elicited IL-2, IL-4 and γ-IFN levels showed good correlation with the degree of protection. On the other hand, biodistribution studies in animals were performed with nanoparticles labelled with either 99mtechnetium or rhodamine B isothiocyanate. The biodistribution revealed that, after instillation, MAN-NP-HS moved from the palpebral area to the nasal region and, the gastrointestinal tract. This profile of distribution was different to that observed for free 99mTcO4− colloids, which remained for at least 24 h in the site of administration. In summary, mannosylated nanoparticles appear to be a safe and suitable adjuvant for conjunctival vaccination.

Radiomarcaje y estudios de biodistribución de nanopartículas poliméricas como adyuvantes para la vacunación oftálmica frente a la brucelosis

Mon, 31 Dec 2012 23:00:00 GMT

Title: Radiomarcaje y estudios de biodistribución de nanopartículas poliméricas como adyuvantes para la vacunación oftálmica frente a la brucelosis Author(s) : Sanchez-Martinez, M. (María); Costa-Martins, R. (Raquel) da; Quincoces, G. (Gemma); Gamazo, C. (Carlos); Caicedo, C. (Carlos); Irache, J.M. (Juan Manuel); Peñuelas, I. (Iván) Abstract: Objetivos: Optimizar el radiomarcaje con 99mTc de nanopartículas de Gantrez® manosiladas y cargadas con el antígeno de Brucella Ovis (Man-NP-HS) y llevar a cabo estudios de biodistribución en ratón tras la administración de las nanopartículas por vía ocular. Metodología: Las Man-NP-HS se obtuvieron por el método de desplazamiento de disolvente. Se purificaron, liofilizaron y caracterizaron. A continuación, se marcaron con 74 MBq de 99mTcO4 - previamente reducido con una disolución ácida de cloruro de estaño, trabajando en ausencia de oxígeno y con un pH final de 4. El rendimiento del marcaje se evaluó mediante TLC. Los estudios de biodistribución se llevaron a cabo en ratones tras la administración oftálmica de la formulación y de un control de 99mTcO4 - libre. Para ello, se sacrificaron los animales a las 2 y a las 24 horas tras la administración ocular y se contaron los órganos en un contador gamma. Resultados: Se obtuvo un rendimiento de marcaje superior al 90%. Los estudios de biodistribución de 99mTc-Man-NP-HS permitieron detectar la actividad concentrada en mucosa nasal y ocular y tracto gastrointestinal tanto a las 2 como a las 24 horas, frente a la biodistribución de 99mTcO4 - libre que permaneció concentrado en la piel alrededor del ojo y en tracto gastrointestinal. Conclusión: Los estudios de biodistribución de 99mTc-Man-NP-HS tras administración oftálmica han permitido demostrar su biodistribución en mucosas y tracto gastrointestinal, característica indispensable como sistema de liberación de antígenos a través de mucosa ocular. Esto, junto con su elevada respuesta inmune, efectiva protección y no virulencia, convierte a estas nanopartículas en una vacuna ideal anti Brucelosis.

Valor de la PET en la recurrencia del cáncer de próstata con PSA < 5 ng/ml

Wed, 31 Dec 2008 23:00:00 GMT

Title: Valor de la PET en la recurrencia del cáncer de próstata con PSA < 5 ng/ml Author(s) : Rioja-Zuazu, J. (Jorge); Rodriguez, M. (Macarena); Rincon-Mayans, A. (Aníbal); Sainz-Sansi, A. (Abel); Zudaire, J.J. (Juan Javier); Martinez-Monge, R. (Rafael); Richter, J.A. (José Ángel); Berian-Polo, J.M. (José María) Abstract: We intend to evaluate the usefulness of PET scans in diagnosing recurrent prostate cancer after a curative attempt using radical treatment. MATERIAL AND METHODS: 92 consecutive prostate cancer patients in biochemical progression following radical surgery (63) or radiation treatment (29) were studied with positron emission tomography (PET). In all cases two scans were performed in the same day (11C-choline and 18F-FDG). PET efficacy was evaluated both globally (by employing the results achieved with both 11C-choline and 18F-FDG) and using both radiotracers independently to detect recurrence in patients with biochemical progression. For this purpose, we used comparison of means for k-independent samples, 2 x 2 and 2 x X contingency tables and ROC curves. RESULTS: 1. Global PET: there is evidence of PET alteration regarding the PSA level (P=.003): the clinical stage (P=.01). There are no statistically significant PET alterations regarding the affected biopsy (uni or bilateral), surgical margins, pathological stage and time to progression. ROC curve PET-PSA is statistically significant (P< .0001) permitting calculation of different cut-off points, with a specificity of 91% (highest) for a PSA of 4.3 ng/ml. 2. PET 18FDG: the area under the ROC curve is statistically significant (P< .0001) with a specificity of 91% for a PSA of 6.51 ng/ml. 3. PET 11choline: the area under the ROC curve is statistically significant (P< .0001) with a specificity of 91% for a PSA of 5.15 ng/ml. CONCLUSIONS: PET is a useful tool for diagnosing prostate cancer recurrence after a curative attempt using radical treatment.

Estudio PET-TC con 18F-fluoro-L-DOPA combinado con el análisis genético para la optimización de la clasificación y tratamiento de un niño con hiperinsulinismo congénito grave

Wed, 31 Dec 2008 23:00:00 GMT

Title: Estudio PET-TC con 18F-fluoro-L-DOPA combinado con el análisis genético para la optimización de la clasificación y tratamiento de un niño con hiperinsulinismo congénito grave Author(s) : Arbizu, J. (J.); Fernandez-Marmiesse, A. (A.); Garrastachu, P. (P.); Martino, E. (E.); Azcona-Sanjulian, M.C. (M.C.); Carracedo, A. (A.); Richter, J.A. (José Ángel) Abstract: Abstract BACKGROUND: Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycaemia in infancy. The differential diagnosis between focal and diffuse forms of CHI is of great importance when planning surgery. The aim of this article is to show the first case of focal CHI diagnosed in Spain using PET-CT imaging combined with genetic analysis. METHODS: A 13 month child with CHI and normal conventional radiological investigations treated with diazoxide, diet control and feeding by gastrostomy is presented. Genetic analysis of ABCC8 and KCNJ11 genes and PET-TAC using 18F-fluoro-L-DOPA were performed. RESULTS: A pathological mutation (G111R) in the paternal allele of ABCC8 was detected. PET-CT scanning using 18F-fluoro-L-DOPA showed a focus of high uptake in the body of the pancreas compatible with adenoma that was hystopathologically confirmed. After surgical resection the patient is asymptomatic without needing either pharmacological treatment or dietetic control. CONCLUSIONS: The combination of genetic analysis and 18F-fluoro-L-DOPA PET-TAC shows a great potential for the identification, location and guideline for surgery in CHI.