36 results on '"Nievas S"'
Search Results
2. Datathons: fostering equitability in data reuse in ecology
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Datathon 2022 Consortium, Jurburg, Stephanie, Álvarez Blanco, Maria Jose, Chatzinotas, Antonis, Kazem, A., König-Ries, B., Babin, D., Smalla, K., Cerecetto, V., Fernandez-Gnecco, G., Covacevich, F., Viruel, E., Bernaschina, Y., Leoni, C., Garaycochea, S., Terra, J.A., Fresia, P., Figuerola, E.L.M., Wall, L.G., Covelli, J.M., Agnello, A.C., Nieto, E.E., Festa, S., Dominici, L.E., Allegrini, M., Zabaloy, M.C., Morales, M.E., Erijman, L., Coniglio, A., Cassán, F.D., Nievas, S., Roldán, D.M., Menes, R., Jauri, P.V., Marrero, C.S., Massa, A.M., Morel Revetria, M.A., Fernández-Scavino, A., Pereira-Mora, L., Martínez, S., Frene, J.P., Datathon 2022 Consortium, Jurburg, Stephanie, Álvarez Blanco, Maria Jose, Chatzinotas, Antonis, Kazem, A., König-Ries, B., Babin, D., Smalla, K., Cerecetto, V., Fernandez-Gnecco, G., Covacevich, F., Viruel, E., Bernaschina, Y., Leoni, C., Garaycochea, S., Terra, J.A., Fresia, P., Figuerola, E.L.M., Wall, L.G., Covelli, J.M., Agnello, A.C., Nieto, E.E., Festa, S., Dominici, L.E., Allegrini, M., Zabaloy, M.C., Morales, M.E., Erijman, L., Coniglio, A., Cassán, F.D., Nievas, S., Roldán, D.M., Menes, R., Jauri, P.V., Marrero, C.S., Massa, A.M., Morel Revetria, M.A., Fernández-Scavino, A., Pereira-Mora, L., Martínez, S., and Frene, J.P.
- Abstract
Approaches to rapidly collecting global biodiversity data are increasingly important, but biodiversity blind spots persist. We organized a three-day Datathon event to improve the openness of local biodiversity data and facilitate data reuse by local researchers. The first Datathon, organized among microbial ecologists in Uruguay and Argentina assembled the largest microbiome dataset in the region to date and formed collaborative consortia for microbiome data synthesis.
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- 2024
3. Beta Enhancers: towards a local dose enhancer device for Boron Neutron Capture Therapy (BNCT) on superficial tumors
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Boggio, E. F., Longhino, J., Provenzano, L., Farias, R., González, S., Nievas, S., Dagrosa, A., MAGJAREVIC, Ratko, Editor-in-chief, Ladyzynsk, Piotr, Series editor, Ibrahim, Fatimah, Series editor, Lacković, Igor, Series editor, Rock, Emilio Sacristan, Series editor, and Jaffray, David A., editor
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- 2015
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4. UnravelingAzospirillum’s colonization ability through microbiological and molecular evidence
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Nievas, S, primary, Coniglio, A, additional, Takahashi, W Y, additional, López, G A, additional, Larama, G, additional, Torres, D, additional, Rosas, S, additional, Etto, R M, additional, Galvão, C W, additional, Mora, V, additional, and Cassán, F, additional
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- 2023
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5. Unraveling Azospirillum's colonization ability through microbiological and molecular evidence.
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Nievas, S, Coniglio, A, Takahashi, W Y, López, G A, Larama, G, Torres, D, Rosas, S, Etto, R M, Galvão, C W, Mora, V, and Cassán, F
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COLONIZATION (Ecology) , *AZOSPIRILLUM , *QUORUM sensing , *CELL aggregation , *BACTERIAL metabolism , *CULTIVARS - Abstract
It is known that members of the bacterial genus Azospirillum can promote the growth of a great variety of plants, an ability harnessed by the industry to create bioproducts aimed to enhance the yield of economically relevant crops. Its versatile metabolism allows this bacterium to adapt to numerous environments, from optimal to extreme or highly polluted. The fact of having been isolated from soil and rhizosphere samples collected worldwide and many other habitats proves its remarkable ubiquity. Azospirillum rhizospheric and endophytic lifestyles are governed by several mechanisms, leading to efficient niche colonization. These mechanisms include cell aggregation and biofilm formation, motility, chemotaxis, phytohormone and other signaling molecules production, and cell-to-cell communication, in turn, involved in regulating Azospirillum interactions with the surrounding microbial community. Despite being infrequently mentioned in metagenomics studies after its introduction as an inoculant, an increasing number of studies detected Azospirillum through molecular tools (mostly 16S rRNA sequencing) as part of diverse, even unexpected, microbiomes. This review focuses on Azospirillum traceability and the performance of the available methods, both classical and molecular. An overview of Azospirillum occurrence in diverse microbiomes and the less-known features explaining its notorious ability to colonize niches and prevail in multiple environments is provided. [ABSTRACT FROM AUTHOR]
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- 2023
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6. Measurement of 10B concentration through autoradiography images in polycarbonate nuclear track detectors
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Portu, A., Bernaola, O.A., Nievas, S., Liberman, S., and Saint Martin, G.
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- 2011
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7. Reference systems for the determination of 10B through autoradiography images: Application to a melanoma experimental model
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Portu, A., Carpano, M., Dagrosa, A., Nievas, S., Pozzi, E., Thorp, S., Cabrini, R., Liberman, S., and Saint Martin, G.
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- 2011
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8. Studies for the application of boron neutron capture therapy to the treatment of differentiated thyroid cancer
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Dagrosa, A., Carpano, M., Perona, M., Thomasz, L., Nievas, S., Cabrini, R., Juvenal, G., and Pisarev, M.
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- 2011
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9. Tumor control and normal tissue complications in BNCT treatment of nodular melanoma: A search for predictive quantities
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González, S.J., Casal, M., Pereira, M.D., Santa Cruz, G.A., Carando, D.G., Blaumann, H., Bonomi, M., Calzetta Larrieu, O., Feld, D., Fernández, C., Gossio, S., Jiménez Rebagliatti, R., Kessler, J., Longhino, J., Menéndez, P., Nievas, S., Roth, B.M.C, and Liberman, S.J.
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- 2009
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10. Boron biodistribution study in colorectal liver metastases patients in Argentina
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Cardoso, J., Nievas, S., Pereira, M., Schwint, A., Trivillin, V., Pozzi, E., Heber, E., Monti Hughes, A., Sanchez, P., Bumaschny, E., Itoiz, M., and Liberman, S.
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- 2009
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11. Improvement of the boron neutron capture therapy (BNCT) by the previous administration of the histone deacetylase inhibitor sodium butyrate for the treatment of thyroid carcinoma
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Perona, M., Rodríguez, C., Carpano, M., Thomasz, L., Nievas, S., Olivera, M., Thorp, S., Curotto, P., Pozzi, E., Kahl, S., Pisarev, M., Juvenal, G., and Dagrosa, A.
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- 2013
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12. Experimental studies of boron neutron capture therapy (BNCT) using histone deacetylase inhibitor (HDACI) sodium butyrate, as a complementary drug for the treatment of poorly differentiated thyroid cancer (PDTC)
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Perona, M., primary, Majdalani, M.E., additional, Rodríguez, C., additional, Nievas, S., additional, Carpano, M., additional, Rossini, A., additional, Longhino, J.M., additional, Cabrini, R., additional, Pisarev, M.A., additional, Juvenal, G.J., additional, and Dagrosa, M.A., additional
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- 2020
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13. Azospirillum brasilense Az39, a model rhizobacterium with AHL quorum quenching capacity
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Gualpa, J., Lopez, G., Nievas, S., Coniglio, A., and Halliday, N.
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Bioproducts ,Quorum sensing ,Microbial physiology ,food and beverages ,Genomics ,biochemical phenomena, metabolism, and nutrition ,Mechanism of action - Abstract
AimsThe aim of this research was to analyze the Quorum sensing (QS) and Quorum quenching (QQ) mechanisms based on N?acyl?L?homoserine lactones (AHLs) in A. brasilense Az39, a strain with remarkable capacity to benefit a wide range of crops under agronomic conditions. Methods and ResultsWe performed an in silico and in vitro analysis of the quorum mechanisms in A. brasilense Az39. The results obtained in vitro using the reporter strains C. violaceum and A. tumefaciens and Liquid Chromatography coupled to Mass?Mass Spectrometry (LC?MS/MS) analysis showed that although Az39 does not produce AHL molecules, it is capable of degrading them by at least two hypothetical enzymes identified by bioinformatics approach, associated to the bacterial cell. In Az39 cultures supplemented with 500 nmol l?1 of the C3 unsubstituted AHLs (C4, C6, C8, C10, C12, C14), AHL levels were lower than in non?inoculated LB media controls. Similar results were observed upon addition of AHLs with hydroxy (OH?) and keto (oxo?) substitutions in carbon 3. These results not only demonstrate the ability of Az39 to degrade AHLs. They also show the wide spectrum of molecules that can be degraded by this bacterium. ConclusionsAlthough A.brasilense Az39 is a silent bacterium unable to produce AHL signals, it is able to interrupt the communications between other bacteria and/or plants by a quorum quenching activity.
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- 2019
14. Azospirillum brasilenseAz39, a model rhizobacterium withAHLquorum‐quenchingcapacity
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Gualpa, J., primary, Lopez, G., additional, Nievas, S., additional, Coniglio, A., additional, Halliday, N., additional, Cámara, M., additional, and Cassán, F., additional
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- 2019
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15. Efecto de la aplicación exógena de fitohormonas sobre la germinación y el desarrollo temprano de semillas de rúcula (Eruca sativa Mill.).
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Oberti, G., Salusso, F., Nievas, S., Torres, D., Mora, V., and Cassán, F.
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- 2022
16. Relevamiento del estado sanitario del cultivo de higuera (Ficus carica) en Puesto Viejo, Colonia Caroya, Córdoba. Situación actual y perspectivas.
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Cargnelutti, M., Vargas, L., Ontivero Urquiza, M., Hiza, L., Barcenilla, M., Haniewicz, G., Ramírez, F., Ortega, J., Díaz, C., Zumelzu, G., Blengini, C., and Nievas, S.
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- 2022
17. Measurement of 10 B concentration through autoradiography images in polycarbonate nuclear track detectors
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Portu, A., primary, Bernaola, O.A., additional, Nievas, S., additional, Liberman, S., additional, and Saint Martin, G., additional
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- 2011
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18. Efecto de la inoculación con Azospirillum brasilense y Bradyrhizobium japonicum sobre la germinación, desarrollo temprano y tardío de rúcula (Eruca sativa Mill.).
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Sargioto, A., Ganum Gorriz, M. J., Nievas, S., Torres, D., Mora, V., and Cassán, F.
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- 2022
19. Enfermedad de Whipple en paciente con fiebre de origen desconocido
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Valdés Álvarez Karen and Nievas Sánchez Marianne
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enfermedad de Whipple ,Tropheryma whippleii ,fiebre de origen desconocido ,Medicine - Abstract
La enfermedad de Whipple es una entidad multisistémica de origen infeccioso causada por una bacteria Gram positiva perteneciente a la familia de los actinomicetos denominada Tropheryma whippleii. Constituye una causa infecciosa infrecuente de fiebre de origen desconocido. Se presenta el caso de un paciente masculino de 65 años con cuadro febril de 3 años de evolución, poliartralgias, edema en miembros inferiores, adenopatías periféricas y diarreas ocasionales. Se describen la evolución clínica, los estudios de laboratorio, imagenológicos e histológicos que permitieron hacer el diagnóstico de enfermedad de Whipple. Se considera que la publicación de este caso es importante pues contribuye a mantener presente esta enfermedad entre las posibilidades diagnósticas de los pacientes con fiebre de origen desconocido, aún por lo atípico de esta forma de presentación.
20. Measurement of 10B concentration through autoradiography images in polycarbonate nuclear track detectors
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Portu, A., Bernaola, O.A., Nievas, S., Liberman, S., and Saint Martin, G.
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NUCLEAR track detectors , *BORON isotopes , *BORON-neutron capture therapy , *AUTORADIOGRAPHY , *EXPERIMENTS , *POLYCARBONATES , *MICROSTRUCTURE - Abstract
Abstract: The determination of the local concentration of boron in the different regions of tissue samples treated by Boron Neutron Capture Therapy (BNCT) could be made through the evaluation of the number of tracks forming autoradiography images. It is necessary to get a “standard” material containing a known amount of 10B, to correlate the number of tracks and boron concentration, i.e. to be used as a reference. Different systems were tested in order to find a suitable standard. Films made of 2% agarose in boron solutions showed a homogeneous distribution of the 10B atoms in the material structure. This system is easy handled and its physical properties are satisfactory. On the other hand, a small volume polycarbonate box was designed to contain 10B solutions of known concentration. This system showed a reduced number of background tracks and a promising behavior in many aspects. There is proportionality between track numbers per surface unit and 10B concentration, and between track numbers per surface unit and neutron fluence. Experimental results were compared to calculated values through formulas developed for thick samples autoradiography. [Copyright &y& Elsevier]
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- 2011
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21. Closo-Carboranyl- and Metallacarboranyl [1,2,3]triazolyl-Decorated Lapatinib-Scaffold for Cancer Therapy Combining Tyrosine Kinase Inhibition and Boron Neutron Capture Therapy
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Mariángeles Kovacs, P. Curotto, S. Nievas, Emiliano Trias, Emiliano C. C. Pozzi, Francesc Teixidor, Hugo Cerecetto, María Fernanda García, Catalina Alamón, S. Thorp, Clara Viñas, Maria Alejandra Dagrosa, Marcos Couto, Agencia Nacional de Investigación e Innovación (Uruguay), Consejo Superior de Investigaciones Científicas (España), Universidad de la República (Uruguay), Ministerio de Economía y Competitividad (España), Couto Marcos, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Química Biológica., Alamón Catalina, Universidad de la República (Uruguay). Facultad de Ciencias. Instituto de Química Biológica., García Melián María Fernanda, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares, Kovacs Mariángeles, Institut Pasteur (Montevideo)., Trias Emiliano, Institut Pasteur (Montevideo)., Nievas S., Pozzi E., Curotto P., Thorp S., Dagrosa M. A., Teixidor Francesc, Viñas Clara, and Cerecetto Hugo, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares
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Boron clusters ,010402 general chemistry ,Lapatinib ,medicine.disease_cause ,01 natural sciences ,Article ,Receptor tyrosine kinase ,03 medical and health sciences ,0302 clinical medicine ,[1,2,3]triazolyl linker ,tyrosine kinase inhibitors ,medicine ,In vitro BNCT effect ,lapatinib ,Receptor ,lcsh:QH301-705.5 ,Tyrosine kinase inhibitors ,biology ,Cell growth ,Chemistry ,General Medicine ,0104 chemical sciences ,boron clusters ,lcsh:Biology (General) ,Apoptosis ,Cell culture ,in vitro BNCT effect ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,Carcinogenesis ,Tyrosine kinase ,medicine.drug - Abstract
© 2020 by the authors., One of the driving forces of carcinogenesis in humans is the aberrant activation of receptors; consequently, one of the most promising mechanisms for cancer treatment is receptor inhibition by chemotherapy. Although a variety of cancers are initially susceptible to chemotherapy, they eventually develop multi-drug resistance. Anti-tumor agents overcoming resistance and acting through two or more ways offer greater therapeutic benefits over single-mechanism entities. In this study, we report on a new family of bifunctional compounds that, offering the possibility of dual action (drug + radiotherapy combinations), may result in significant clinical benefits. This new family of compounds combines two fragments: the drug fragment is a lapatinib group, which inhibits the tyrosine kinase receptor activity, and an icosahedral boron cluster used as agents for neutron capture therapy (BNCT). The developed compounds were evaluated in vitro against different tyrosine kinase receptors (TKRs)-expressing tumoral cells, and in vitro–BNCT experiments were performed for two of the most promising hybrids, 19 and 22. We identified hybrid 19 with excellent selectivity to inhibit cell proliferation and ability to induce necrosis/apoptosis of glioblastoma U87 MG cell line. Furthermore, derivative 22, bearing a water-solubility-enhancing moiety, showed moderate inhibition of cell proliferation in both U87 MG and colorectal HT-29 cell lines. Additionally, the HT-29 cells accumulated adequate levels of boron after hybrids 19 and 22 incubations rendering, and after neutron irradiation, higher BNCT-effects than BPA. The attractive profile of developed hybrids makes them interesting agents for combined therapy., This research was funded by FCE-ANII (FCE_3_2018_1_148288), Institut Pasteur de Montevideo— FOCEM. M.C., M.F.G., E.T., and H.C. are Sistema Nacional de Investigadores- Agencia Nacional de Investigación e Innovación (ANII) researchers. M.C. thanks CSIC-Universidad de la República (UdelaR) (Grupo I + D, CSIC-421) for his scholarships. M.C. thanks funding from ANII for his doctoral-scholarship (POS_NAC_2015_1_110068). C.V. and F.T. thanks MINECO (CTQ2016-75150-R) for financial support.
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- 2020
22. Reference systems for the determination of 10B through autoradiography images: Application to a melanoma experimental model
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Portu, A., Carpano, M., Dagrosa, A., Nievas, S., Pozzi, E., Thorp, S., Cabrini, R., Liberman, S., and Saint Martin, G.
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BORON isotopes , *AUTORADIOGRAPHY , *MELANOMA , *PHYSICS experiments , *NUCLEAR track detectors , *LABORATORY mice - Abstract
Abstract: The amount of 10B in tissue samples may be determined by measuring the track density in the autoradiography image produced on a nuclear track detector. Different systems were evaluated as reference standards to be used for a quantitative evaluation of boron concentration. The obtained calibration curves were applied to evaluate the concentration of 10B in melanoma tumour of NIH nude mice after a biodistribution study. The histological features observed in the tissue sections were accurately reproduced by the autoradiography images. [Copyright &y& Elsevier]
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- 2011
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23. Quality improvement collaborative for improving patient care delivery in Argentine public health sector intensive care units.
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Loudet CI, Jorro Barón F, Reina R, Arias López MDP, Alegría SL, Barrios CDV, Buffa R, Cabana ML, Cunto ER, Fernández Nievas S, García MA, Gibbons L, Izzo G, Llanos MN, Meregalli C, Joaquín Mira J, Ratto ME, Rivet ML, Roberti J, Silvestri AM, Tévez A, Uranga LJ, Zakalik G, Rodríguez V, and García-Elorrio E
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- Humans, Argentina, Male, Female, Personal Protective Equipment statistics & numerical data, Middle Aged, Pandemics prevention & control, Delivery of Health Care standards, Adult, Public Health methods, Health Personnel statistics & numerical data, Health Personnel psychology, Interrupted Time Series Analysis methods, Quality Improvement, COVID-19 prevention & control, COVID-19 epidemiology, Intensive Care Units organization & administration, Intensive Care Units statistics & numerical data, SARS-CoV-2
- Abstract
Background: The demand for healthcare services during the COVID-19 pandemic was excessive for less-resourced settings, with intensive care units (ICUs) taking the heaviest toll., Objective: The aim was to achieve adequate personal protective equipment (PPE) use in 90% of patient encounters, to reach 90% compliance with objectives of patient flow (OPF) and to provide emotional support tools to 90% of healthcare workers (HCWs)., Methods: We conducted a quasi-experimental study with an interrupted time-series design in 14 ICUs in Argentina. We randomly selected adult critically ill patients admitted from July 2020 to July 2021 and active HCWs in the same period. We implemented a quality improvement collaborative (QIC) with a baseline phase (BP) and an intervention phase (IP). The QIC included learning sessions, periods of action and improvement cycles (plan-do-study-act) virtually coached by experts via platform web-based activities. The main study outcomes encompassed the following elements: proper utilisation of PPE, compliance with nine specific OPF using daily goal sheets through direct observations and utilisation of a web-based tool for tracking emotional well-being among HCWs., Results: We collected 7341 observations of PPE use (977 in BP and 6364 in IP) with an improvement in adequate use from 58.4% to 71.9% (RR 1.2, 95% CI 1.17 to 1.29, p<0.001). We observed 7428 patient encounters to evaluate compliance with 9 OPF (879 in BP and 6549 in IP) with an improvement in compliance from 53.9% to 67% (RR 1.24, 95% CI 1.17 to 1.32, p<0.001). The results showed that HCWs did not use the support tool for self-mental health evaluation as much as expected., Conclusion: A QIC was effective in improving healthcare processes and adequate PPE use, even in the context of a pandemic, indicating the possibility of expanding QIC networks nationwide to improve overall healthcare delivery. The limited reception of emotional support tools requires further analyses., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2024
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24. Datathons: fostering equitability in data reuse in ecology.
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Jurburg SD, Álvarez Blanco MJ, Chatzinotas A, Kazem A, König-Ries B, Babin D, Smalla K, Cerecetto V, Fernandez-Gnecco G, Covacevich F, Viruel E, Bernaschina Y, Leoni C, Garaycochea S, Terra JA, Fresia P, Figuerola ELM, Wall LG, Covelli JM, Agnello AC, Nieto EE, Festa S, Dominici LE, Allegrini M, Zabaloy MC, Morales ME, Erijman L, Coniglio A, Cassán FD, Nievas S, Roldán DM, Menes R, Jauri PV, Marrero CS, Massa AM, Revetria MAM, Fernández-Scavino A, Pereira-Mora L, Martínez S, and Frene JP
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- Argentina, Uruguay, Biodiversity, Ecology, Microbiota
- Abstract
Approaches to rapidly collecting global biodiversity data are increasingly important, but biodiversity blind spots persist. We organized a three-day Datathon event to improve the openness of local biodiversity data and facilitate data reuse by local researchers. The first Datathon, organized among microbial ecologists in Uruguay and Argentina assembled the largest microbiome dataset in the region to date and formed collaborative consortia for microbiome data synthesis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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25. Quality improvement collaborative to optimize heart failure care in patients from a network of clinics in Argentina during the COVID-19 pandemic.
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Jorro-Barón F, Suárez-Anzorena I, Roberti J, Mazzoni A, Vita T, Alonso JP, Villarejo A, de la Vega B, Ditata F, Facta Á, Flores D, Mastantuono C, Saa R, San-Dámaso E, Vega G, Renedo F, Fernández A, Fernández-Nievas S, and García-Elorrio E
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- Humans, Pandemics, Quality Improvement, Argentina epidemiology, Patient Readmission, COVID-19 epidemiology, COVID-19 therapy, Heart Failure therapy
- Abstract
Heart failure (HF) is a major clinical and public health problem associated with significant mortality, morbidity, and health-care costs. Despite the existence of evidence-based guidelines for the optimal treatment of HF, the quality of care remains suboptimal. Our aim was to increase the use a care bundle in 50% of enrolled subjects during their hospitalization and discharge and to reduce their readmission for HF causes by 10%. We conducted an uncontrolled before-after study in eight hospitals in Argentina to evaluate the effect of a quality improvement intervention on the use of an HF care bundle in patients with HF New York Heart Association (NYHA) Class II-III. The HF bundle of care included medication, continuum of care, lifestyle habits, and predischarge examinations. Training and follow-up of multidisciplinary teams in each center were performed through learning sessions and plan-do-study-act improvement cycles. Data collectors reviewed bundle compliance in the health records of recruited patients after their hospital discharge and verified readmissions through phone calls to patients within 30-40 days after discharge. We recruited 200 patients (83 before and 127 during the intervention phase), and bundle compliance increased from 9.6% to 28.3% [odds ratio 3.71, 95% confidence interval (8.46; 1.63); P = .002]. Despite a slow improvement during the first months, bundle compliance gained momentum near the end of the intervention surpassing 80%. We observed a non-significant decreased readmission rate within 30 days of discharge due to HF in the postintervention period [8.4% vs. 5.5%, odds ratio 0.63, 95% CI (1.88; 0.21); P = .410]. Qualitative analysis showed that members of the intervention teams acknowledged the improvement of work organization and standardization of care, teamwork, shared mental model, and health record completeness as well as the utility of training fellows. Despite the challenges related to the pandemic, better care of patients with HF NYHA Class II-III was possible through simple interventions and collaborative work. Graphical abstract., (© The Author(s) 2023. Published by Oxford University Press on behalf of International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2023
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26. A Potential Boron Neutron Capture Therapy Agent Selectively Suppresses High-Grade Glioma: In Vitro and in Vivo Exploration.
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Alamón C, Dávila B, García MF, Nievas S, Dagrosa MA, Thorp S, Kovacs M, Trias E, Faccio R, Gabay M, Zeineh N, Weizman A, Teixidor F, Viñas C, Gavish M, Cerecetto H, and Couto M
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- Mice, Humans, Animals, Boron, Boron Compounds pharmacology, Boron Compounds therapeutic use, Brain Neoplasms drug therapy, Brain Neoplasms radiotherapy, Brain Neoplasms metabolism, Boron Neutron Capture Therapy, Glioma drug therapy, Glioma radiotherapy, Glioma metabolism, Glioblastoma drug therapy
- Abstract
Glioblastoma (GBM), as the most central nervous system (CNS) intractable disease, has spoiled millions of lives due to its high mortality. Even though several efforts have been made, the existing treatments have had limited success. In this sense, we studied a lead compound, the boron-rich selective epidermal growth factor receptor (EGFR)-inhibitor hybrid 1 , as a potential drug for GBM treatment. For this end, we analyzed the in vitro activity of hybrid 1 in a glioma/primary astrocytes coculture, studying cellular death types triggered by treatment with this compound and its cellular localizations. Additionally, hybrid 1 concentrated boron in glioma cells selectively and more effectively than the boron neutron capture therapy (BNCT)-clinical agent
10 B-l-boronophenylalanine and thus displayed a better in vitro -BNCT effect. This encouraged us to analyze hybrid 1 in vivo . Therefore, immunosuppressed mice bearing U87 MG human GBM were treated with both 1 and 1 encapsulated in a modified liposome (recognized by brain-blood barrier peptide transporters), and we observed a potent in vivo per se antitumor activity (tumor size decrease and animal survival increase). These data demonstrate that 1 could be a promising new targeted therapy for GBM.- Published
- 2023
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27. Genome-based reclassification of Azospirillum brasilense Az39 as the type strain of Azospirillum argentinense sp. nov.
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Dos Santos Ferreira N, Coniglio A, Puente M, Sant'Anna FH, Maroniche G, García J, Molina R, Nievas S, Volpiano CG, Ambrosini A, Passaglia LMP, Pedraza RO, Reis VM, Zilli JÉ, and Cassan F
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- Bacterial Typing Techniques, Base Composition, DNA, Bacterial genetics, Fatty Acids chemistry, Nucleic Acid Hybridization, Phospholipids analysis, Phylogeny, RNA, Ribosomal, 16S genetics, Sequence Analysis, DNA, Ubiquinone analysis, Azospirillum brasilense genetics
- Abstract
Strain Az39
T of Azospirillum is a diazotrophic plant growth-promoting bacterium isolated in 1982 from the roots of wheat plants growing in Marcos Juárez, Córdoba, Argentina. It produces indole-3-acetic acid in the presence of l-tryptophan as a precursor, grows at 20-38 °C (optimal 38 °C), and the cells are curved or spiral-shaped, with diameters ranging from 0.5-0.9 to 1.8-2.2 µm. They contain C16 : 0 , C18 : 0 and C18 : 1 ω 7 c / ω 6 c as the main fatty acids. Phylogenetic analysis of its 16S rRNA gene sequence confirmed that this strain belongs to the genus Azospirillum , showing a close relationship with Azospirillum baldaniorum Sp245T , Azospirillum brasilense Sp7T and Azospirillum formosense CC-Nfb-7T . Housekeeping gene analysis revealed that Az39T , together with five strains of the genus (Az19, REC3, BR 11975, MTCC4035 and MTCC4036), form a cluster apart from A. baldaniorum Sp245T , A. brasilense Sp7T and A. formosense CC-Nfb-7T . Average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) between Az39T and the aforementioned type strains revealed values below 96 %, the circumscription limit for the species delineation (ANI: 95.3, 94.1 and 94.0 %; dDDH: 62.9, 56.3 and 55.6 %). Furthermore, a phylogeny evaluation of the core proteome, including 809 common shared proteins, showed an independent grouping of Az39T , Az19, REC3, BR 11975, MTCC4035 and MTCC4036. The G+C content in the genomic DNA of these six strains varied from 68.3 to 68.5 %. Based on the combined phylogenetic, genomic and phenotypic characterization presented here, we consider that strain Az39T , along with strains Az19, REC3, BR 11975, MTCC4035 and MTCC4036, are members of a new Azospirillum species, for which the name Azospirillum argentinense sp. nov. is proposed. The type strain is Az39T (=LBPCV39T =BR 148428T =CCCT 22.01T ).- Published
- 2022
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28. What Do We Know About the Publications Related with Azospirillum? A Metadata Analysis.
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Cassán F, López G, Nievas S, Coniglio A, Torres D, Donadio F, Molina R, and Mora V
- Subjects
- Azospirillum classification, Plant Development, Plant Roots microbiology, Azospirillum metabolism, Host Microbial Interactions physiology, Plant Growth Regulators, Plants microbiology
- Abstract
Azospirillum is one of the most successful plant growth-promoting bacteria (PGPB) genera and it is considered a study model for plant-bacteria interactions. Because of that, a wide broad of topics has been boarded and discussed in a significant number of publications in the last four decades. Using the Scopus® database, we conducted a bibliographic search in order to analyze the number and type of publications, the authors responsible of these contributions, and the origin of the researchers, as well as the keywords and journals selected by the authors, among other related characteristics, with the aim to understand some less addressed details about the work done with Azospirillum worldwide since its discovery in 1925. Despite that the largest numbers of publications about this bacterium were obtained between the 1970 and 1980s, there is still a linear increase tendency in the number of published works. Understanding the mechanisms involved in the ability of these bacteria to promote growth in a wide broad of plant species under both laboratory and field conditions has been a preferential target for these published articles. This tendency could be considered a cause or consequence of the current increase in the number of commercial products formulated with Azospirillum around the world and a catalyzer for the increase of published articles along time.
- Published
- 2021
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29. Bimodal Therapeutic Agents Against Glioblastoma, One of the Most Lethal Forms of Cancer.
- Author
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Couto M, Alamón C, Nievas S, Perona M, Dagrosa MA, Teixidor F, Cabral P, Viñas C, and Cerecetto H
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- Animals, Boron Compounds, Cell Line, Tumor, Humans, Mice, Phenylalanine, Antineoplastic Agents pharmacology, Antineoplastic Agents therapeutic use, Boron Neutron Capture Therapy, Brain Neoplasms drug therapy, Brain Neoplasms radiotherapy, Cell Survival drug effects, Glioblastoma drug therapy, Glioblastoma radiotherapy, Pharmaceutical Preparations
- Abstract
About 95 % of people diagnosed with glioblastoma die within five years. Glioblastoma is the most aggressive central nervous system tumour. It is necessary to make progress in the glioblastoma treatment so that advanced chemotherapy drugs or radiation therapy or, ideally, two-in-one hybrid systems should be implemented. Tyrosine kinase receptors-inhibitors and boron neutron capture therapy (BNCT), together, could provide a therapeutic strategy. In this work, sunitinib decorated-carborane hybrids were prepared and biologically evaluated identifying excellent antitumoral- and BNCT-agents. One of the selected hybrids was studied against glioma-cells and found to be 4 times more cytotoxic than sunitinib and 1.7 times more effective than
10 B-boronophenylalanine fructose complex when the cells were irradiated with neutrons., (© 2020 Wiley-VCH GmbH.)- Published
- 2020
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30. Closo -Carboranyl- and Metallacarboranyl [1,2,3]triazolyl-Decorated Lapatinib-Scaffold for Cancer Therapy Combining Tyrosine Kinase Inhibition and Boron Neutron Capture Therapy.
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Couto M, Alamón C, García MF, Kovacs M, Trias E, Nievas S, Pozzi E, Curotto P, Thorp S, Dagrosa MA, Teixidor F, Viñas C, and Cerecetto H
- Subjects
- Animals, Animals, Newborn, Boron Compounds chemical synthesis, Boron Compounds chemistry, Cell Line, Tumor, Cell Survival drug effects, Cell Survival radiation effects, Humans, Inhibitory Concentration 50, Lapatinib chemistry, Lapatinib pharmacology, Mice, Protein Kinase Inhibitors pharmacology, Triazines chemical synthesis, Triazines chemistry, Boron Neutron Capture Therapy, Lapatinib therapeutic use, Neoplasms drug therapy, Protein Kinase Inhibitors therapeutic use
- Abstract
One of the driving forces of carcinogenesis in humans is the aberrant activation of receptors; consequently, one of the most promising mechanisms for cancer treatment is receptor inhibition by chemotherapy. Although a variety of cancers are initially susceptible to chemotherapy, they eventually develop multi-drug resistance. Anti-tumor agents overcoming resistance and acting through two or more ways offer greater therapeutic benefits over single-mechanism entities. In this study, we report on a new family of bifunctional compounds that, offering the possibility of dual action (drug + radiotherapy combinations), may result in significant clinical benefits. This new family of compounds combines two fragments: the drug fragment is a lapatinib group, which inhibits the tyrosine kinase receptor activity, and an icosahedral boron cluster used as agents for neutron capture therapy (BNCT). The developed compounds were evaluated in vitro against different tyrosine kinase receptors (TKRs)-expressing tumoral cells, and in vitro-BNCT experiments were performed for two of the most promising hybrids, 19 and 22 . We identified hybrid 19 with excellent selectivity to inhibit cell proliferation and ability to induce necrosis/apoptosis of glioblastoma U87 MG cell line. Furthermore, derivative 22 , bearing a water-solubility-enhancing moiety, showed moderate inhibition of cell proliferation in both U87 MG and colorectal HT-29 cell lines. Additionally, the HT-29 cells accumulated adequate levels of boron after hybrids 19 and 22 incubations rendering, and after neutron irradiation, higher BNCT-effects than BPA . The attractive profile of developed hybrids makes them interesting agents for combined therapy.
- Published
- 2020
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31. Azospirillum brasilense Az39, a model rhizobacterium with AHL quorum-quenching capacity.
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Gualpa J, Lopez G, Nievas S, Coniglio A, Halliday N, Cámara M, and Cassán F
- Subjects
- Agrobacterium tumefaciens metabolism, Azospirillum brasilense genetics, Azospirillum brasilense metabolism, Bacterial Proteins genetics, Bacterial Proteins metabolism, Chromatography, Liquid, Chromobacterium metabolism, Mass Spectrometry, Quorum Sensing genetics, Acyl-Butyrolactones metabolism, Azospirillum brasilense physiology, Quorum Sensing physiology
- Abstract
Aims: The aim of this research was to analyse the quorum-sensing (QS) and quorum-quenching (QQ) mechanisms based on N-acyl-l-homoserine lactones (AHLs) in Azospirillum brasilense Az39, a strain with remarkable capacity to benefit a wide range of crops under agronomic conditions., Methods and Results: We performed an in silico and in vitro analysis of the quorum mechanisms in A. brasilense Az39. The results obtained in vitro using the reporter strains Chromobacterium violaceum and Agrobacterium tumefaciens and liquid chromatography coupled with mass-mass spectrometry analysis showed that although Az39 does not produce AHL molecules, it is capable of degrading them by at least two hypothetical enzymes identified by bioinformatics approach, associated with the bacterial cell. In Az39 cultures supplemented with 500 nmol l
-1 of the C3 unsubstituted AHLs (C4, C6, C8, C10, C12, C14), AHL levels were lower than in noninoculated LB media controls. Similar results were observed upon the addition of AHLs with hydroxy (OH-) and keto (oxo-) substitutions in C3. These results not only demonstrate the ability of Az39 to degrade AHLs. They also show the wide spectrum of molecules that can be degraded by this bacterium., Conclusions: Although A. brasilense Az39 is a silent bacterium unable to produce AHL signals, it is able to interrupt the communications between other bacteria and/or plants by a QQ activity., Significance and Impact of the Study: This is the first report confirming by unequivocal methodology the ability of A. brasilense, one of the most agriculturally used benefic bacteria around the world, to degrade AHLs by a QQ mechanism., (© 2019 The Society for Applied Microbiology.)- Published
- 2019
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32. Experimental Studies of Boronophenylalanine ((10)BPA) Biodistribution for the Individual Application of Boron Neutron Capture Therapy (BNCT) for Malignant Melanoma Treatment.
- Author
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Carpano M, Perona M, Rodriguez C, Nievas S, Olivera M, Santa Cruz GA, Brandizzi D, Cabrini R, Pisarev M, Juvenal GJ, and Dagrosa MA
- Subjects
- Animals, Body Temperature physiology, Cell Line, Tumor, Humans, Ki-67 Antigen analysis, Melanoma pathology, Melanoma radiotherapy, Mice, Mice, Nude, Platelet Endothelial Cell Adhesion Molecule-1 analysis, Radioisotopes pharmacokinetics, Skin Neoplasms, Tissue Distribution, Tumor Burden, Melanoma, Cutaneous Malignant, Boron pharmacokinetics, Boron Compounds pharmacokinetics, Boron Neutron Capture Therapy, Melanoma metabolism, Phenylalanine pharmacokinetics
- Abstract
Purpose: Patients with the same histopathologic diagnosis of cutaneous melanoma treated with identical protocols of boron neutron capture therapy (BNCT) have shown different clinical outcomes. The objective of the present studies was to evaluate the biodistribution of boronophenilalanina ((10)BPA) for the potential application of BNCT for the treatment of melanoma on an individual basis., Methods and Materials: The boronophenilalanine (BPA) uptake was evaluated in 3 human melanoma cell lines: MEL-J, A375, and M8. NIH nude mice were implanted with 4 10(6) MEL-J cells, and biodistribution studies of BPA (350 mg/kg intraperitoneally) were performed. Static infrared imaging using a specially modified infrared camera adapted to measure the body infrared radiance of small animals was used. Proliferation marker, Ki-67, and endothelial marker, CD31, were analyzed in tumor samples., Results: The in vitro studies demonstrated different patterns of BPA uptake for each analyzed cell line (P<.001 for MEL-J and A375 vs M8 cells). The in vivo studies showed a maximum average boron concentration of 25.9 ± 2.6 μg/g in tumor, with individual values ranging between 11.7 and 52.0 μg/g of (10)B 2 hours after the injection of BPA. Tumor temperature always decreased as the tumors increased in size, with values ranging between 37 °C and 23 °C. A significant correlation between tumor temperature and tumor-to-blood boron concentration ratio was found (R(2) = 0.7, rational function fit). The immunohistochemical studies revealed, in tumors with extensive areas of viability, a high number of positive cells for Ki-67, blood vessels of large diameter evidenced by the marker CD31, and a direct logistic correlation between proliferative status and boron concentration difference between tumor and blood (R(2) = 0.81, logistic function fit)., Conclusion: We propose that these methods could be suitable for designing new screening protocols applied before melanoma BNCT treatment for each individual patient and lesion., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
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33. Biodistribution of sodium borocaptate (BSH) for boron neutron capture therapy (BNCT) in an oral cancer model.
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Garabalino MA, Heber EM, Monti Hughes A, González SJ, Molinari AJ, Pozzi EC, Nievas S, Itoiz ME, Aromando RF, Nigg DW, Bauer W, Trivillin VA, and Schwint AE
- Subjects
- 9,10-Dimethyl-1,2-benzanthracene, Animals, Carcinogens, Cricetinae, Disease Models, Animal, Mesocricetus, Mouth Neoplasms chemically induced, Tissue Distribution, Borohydrides pharmacokinetics, Boron Neutron Capture Therapy, Mouth Neoplasms metabolism, Sulfhydryl Compounds pharmacokinetics
- Abstract
Boron neutron capture therapy (BNCT) is based on selective accumulation of ¹⁰B carriers in tumor followed by neutron irradiation. We previously proved the therapeutic success of BNCT mediated by the boron compounds boronophenylalanine and sodium decahydrodecaborate (GB-10) in the hamster cheek pouch oral cancer model. Based on the clinical relevance of the boron carrier sodium borocaptate (BSH) and the knowledge that the most effective way to optimize BNCT is to improve tumor boron targeting, the specific aim of this study was to perform biodistribution studies of BSH in the hamster cheek pouch oral cancer model and evaluate the feasibility of BNCT mediated by BSH at nuclear reactor RA-3. The general aim of these studies is to contribute to the knowledge of BNCT radiobiology and optimize BNCT for head and neck cancer. Sodium borocaptate (50 mg ¹⁰B/kg) was administered to tumor-bearing hamsters. Groups of 3-5 animals were killed humanely at nine time-points, 3-12 h post-administration. Samples of blood, tumor, precancerous pouch tissue, normal pouch tissue and other clinically relevant normal tissues were processed for boron measurement by optic emission spectroscopy. Tumor boron concentration peaked to therapeutically useful boron concentration values of 24-35 ppm. The boron concentration ratio tumor/normal pouch tissue ranged from 1.1 to 1.8. Pharmacokinetic curves showed that the optimum interval between BSH administration and neutron irradiation was 7-11 h. It is concluded that BNCT mediated by BSH at nuclear reactor RA-3 would be feasible.
- Published
- 2013
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34. Boron neutron capture therapy (BNCT) for the treatment of liver metastases: biodistribution studies of boron compounds in an experimental model.
- Author
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Garabalino MA, Monti Hughes A, Molinari AJ, Heber EM, Pozzi EC, Cardoso JE, Colombo LL, Nievas S, Nigg DW, Aromando RF, Itoiz ME, Trivillin VA, and Schwint AE
- Subjects
- Animals, Disease Models, Animal, Female, Liver Neoplasms secondary, Male, Rats, Boron Compounds pharmacokinetics, Boron Compounds therapeutic use, Boron Neutron Capture Therapy, Liver Neoplasms metabolism, Liver Neoplasms radiotherapy
- Abstract
We previously demonstrated the therapeutic efficacy of different boron neutron capture therapy (BNCT) protocols in an experimental model of oral cancer. BNCT is based on the selective accumulation of (10)B carriers in a tumor followed by neutron irradiation. Within the context of exploring the potential therapeutic efficacy of BNCT for the treatment of liver metastases, the aim of the present study was to perform boron biodistribution studies in an experimental model of liver metastases in rats. Different boron compounds and administration conditions were assayed to determine which administration protocols would potentially be therapeutically useful in in vivo BNCT studies at the RA-3 nuclear reactor. A total of 70 BDIX rats were inoculated in the liver with syngeneic colon cancer cells DHD/K12/TRb to induce the development of subcapsular tumor nodules. Fourteen days post-inoculation, the animals were used for biodistribution studies. We evaluated a total of 11 administration protocols for the boron compounds boronophenylalanine (BPA) and GB-10 (Na(2)(10)B(10)H(10)), alone or combined at different dose levels and employing different administration routes. Tumor, normal tissue, and blood samples were processed for boron measurement by atomic emission spectroscopy. Six protocols proved potentially useful for BNCT studies in terms of absolute boron concentration in tumor and preferential uptake of boron by tumor tissue. Boron concentration values in tumor and normal tissues in the liver metastases model show it would be feasible to reach therapeutic BNCT doses in tumor without exceeding radiotolerance in normal tissue at the thermal neutron facility at RA-3., (© Springer-Verlag 2010)
- Published
- 2011
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35. Boron neutron capture therapy (BNCT) inhibits tumor development from precancerous tissue: an experimental study that supports a potential new application of BNCT.
- Author
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Monti Hughes A, Heber EM, Pozzi E, Nigg DW, Calzetta O, Blaumann H, Longhino J, Nievas SI, Aromando RF, Itoiz ME, Trivillin VA, and Schwint AE
- Subjects
- 9,10-Dimethyl-1,2-benzanthracene toxicity, Animals, Borohydrides pharmacokinetics, Borohydrides therapeutic use, Boron Compounds pharmacokinetics, Boron Compounds therapeutic use, Cricetinae, Mouth Neoplasms radiotherapy, Neoplasm Recurrence, Local radiotherapy, Neoplasms, Second Primary radiotherapy, Phenylalanine analogs & derivatives, Phenylalanine pharmacokinetics, Phenylalanine therapeutic use, Precancerous Conditions chemically induced, Precancerous Conditions metabolism, Precancerous Conditions pathology, Radiation-Sensitizing Agents pharmacokinetics, Radiation-Sensitizing Agents therapeutic use, Sulfhydryl Compounds pharmacokinetics, Sulfhydryl Compounds therapeutic use, Tissue Distribution, Boron Neutron Capture Therapy methods, Precancerous Conditions radiotherapy
- Abstract
We previously demonstrated the efficacy of boron neutron capture therapy (BNCT) mediated by boronophenylalanine (BPA), GB-10 (Na(2)(10)B(10)H(10)) and (GB-10+BPA) to control tumors, with no normal tissue radiotoxicity, in the hamster cheek pouch oral cancer model. Herein we developed a novel experimental model of field-cancerization and precancerous lesions (globally termed herein precancerous tissue) in the hamster cheek pouch to explore the long-term potential inhibitory effect of the same BNCT protocols on the development of second primary tumors from precancerous tissue. Clinically, second primary tumor recurrences occur in field-cancerized tissue, causing therapeutic failure. We performed boron biodistribution studies followed by in vivo BNCT studies, with 8 months follow-up. All 3 BNCT protocols induced a statistically significant reduction in tumor development from precancerous tissue, reaching a maximum inhibition of 77-100%. The inhibitory effect of BPA-BNCT and (GB-10+BPA)-BNCT persisted at 51% at the end of follow-up (8 months), whereas for GB-10-BNCT it faded after 2 months. Likewise, beam-only elicited a significant but transient reduction in tumor development. No normal tissue radiotoxicity was observed. At 8 months post-treatment with BPA-BNCT or (GB-10+BPA)-BNCT, the precancerous pouches that did not develop tumors had regained the macroscopic and histological appearance of normal (non-cancerized) pouches. A potential new clinical application of BNCT would lie in its capacity to inhibit local regional recurrences.
- Published
- 2009
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36. BNCT for skin melanoma in extremities: updated Argentine clinical results.
- Author
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Menéndez PR, Roth BM, Pereira MD, Casal MR, González SJ, Feld DB, Santa Cruz GA, Kessler J, Longhino J, Blaumann H, Jiménez Rebagliati R, Calzetta Larrieu OA, Fernández C, Nievas SI, and Liberman SJ
- Subjects
- Aged, Argentina, Boron Compounds therapeutic use, Female, Humans, Leg, Male, Middle Aged, Phenylalanine analogs & derivatives, Phenylalanine therapeutic use, Radiation-Sensitizing Agents therapeutic use, Radiotherapy Dosage, Radiotherapy Planning, Computer-Assisted, Boron Neutron Capture Therapy methods, Melanoma radiotherapy, Skin Neoplasms radiotherapy
- Abstract
As part of phase I/II melanoma BNCT clinical trial conducted in Argentina in a cooperative effort of the Argentine Atomic Energy Commission (CNEA) and the Oncology Institute Angel H. Roffo (IOAHR), 7 patients (6 female-1 male) received eight treatment sessions covering ten anatomical areas located in extremities. Mean age of the patients was 64 years (51-74). The treatments were performed between October 2003 and June 2007. All patients presented multiple subcutaneous skin metastases of melanoma and received an infusion containing approximately 14 gr/m(2) of (10)borophenyl-alanine (BPA) followed by the exposition of the area to a mixed thermal-epithermal neutron beam at the RA-6 reactor. The maximum prescribed dose to normal skin ranged from 16.5 to 24 Gy-Eq and normal tissue administered dose varied from 15.8 to 27.5 Gy-Eq. Considering evaluable nodules, 69.3% of overall response and 30.7% of no changes were seen. The toxicity was acceptable, with 3 out of 10 evaluable areas showing ulceration (30% toxicity grade 3).
- Published
- 2009
- Full Text
- View/download PDF
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