José Jiménez Ortega - Academia.edu (original) (raw)
Uploads
Papers by José Jiménez Ortega
Biodrugs, 2010
Background: HIV infection of the CNS is the principle cause of HIV-associated dementia in adults ... more Background: HIV infection of the CNS is the principle cause of HIV-associated dementia in adults and encephalopathy in children. Gene therapy techniques such as small interfering RNA (siRNA) possess great potential in drug development, but first they must overcome the key obstacle of reaching the interior of the affected cells. A successful delivery vector for anti-HIV drugs that is capable of crossing the blood-brain barrier (BBB) could provide a way of addressing this issue. Non-viral vectors such as dendrimers offer a means for effectively delivering and transfecting siRNA to the target cells. Objective: To evaluate the application of gene therapy for reducing HIV replication in human astrocytes. Methods: We used the 2G-NN16 amino-terminated carbosilane dendrimer as a method for delivering siRNA to HIV-infected human astrocytes. We tested the cytotoxicity in human astrocytoma cells caused by 2G-NN16 and dendriplexes formed with siRNA (siRNA 2G-NN16) by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium-bromide (MTT) and lactate dehydrogenase assays. The ability to transfect human astrocytes with siRNA 2G-NN16 dendriplexes was tested by flow cytometry and immunofluorescence microscopy. To assess the potential capability of siRNA 2G-NN16 dendriplexes for crossing the BBB, we used an in vitro transcytosis assay with bovine brain microvascular endothelial cells. HIV-1 inhibition assays using 2G-NN16 and siRNA 2G-NN16 dendriplexes were determined by quantification of the viral load from culture supernatants of the astrocytes. Results: A gradual time-controlled degradation of the 2G-NN16 dendrimer and liberation of its siRNA cargo between 12 and 24 hours was observed via gel electrophoresis. There was no cytotoxicity in HIVinfected or non-infected human astrocytoma cells when treated with up to 24 mg mL of 2G-NN16 dendrimer or siRNA 2G-NN16 dendriplexes, and siRNA 2G-NN16 dendriplexes were seen to successfully transfect human astrocytes even after crossing an in vitro BBB model. More interestingly, transfected siRNA was observed to exert a biologic effect, as dendriplexes were shown to down-regulate the housekeeping gene GAPDH and to reduce replication of HIV-1 strains X4-HIV NL4-3 and R5-HIV BaL in human astrocytes. Conclusions: The 2G-NN16 dendrimer successfully delivers and transfects siRNA to HIV-infected human astrocytes and achieves gene silencing without causing cytotoxicity.
Pharmaceutical Research, 2009
Purpose To study the effect of a non-viral vector (carbosilane dendrimer) to efficiently deliver ... more Purpose To study the effect of a non-viral vector (carbosilane dendrimer) to efficiently deliver small interfering RNA to postmitotic neurons to study the function of hypoxia-inducible factor-1α (HIF1-α) during chemical hypoxia-mediated neurotoxicity. Methods Chemical hypoxia was induced in primary rat cortical neurons by exposure to CoCl2. HIF1-α levels were determined by Western Blot and toxicity was evaluated by both MTT and LDH assays. Neurons were incubated with dendriplexes containing anti-HIF1-α siRNA and both uptake and HIF1-α knockdown efficiency were evaluated. Results We report that a non-viral vector (carbosilane dendrimer) can deliver specific siRNA to neurons and selectively block HIF1-α synthesis with similar efficiency to that achieved by viral vectors. Using this method, we have found that this transcription factor plays a neuroprotective role during the early phase of chemical hypoxia-mediated neurotoxicity. Conclusion This work represents a proof-of-concept for the use of carbosilane dendrimers to deliver specific siRNA to postmitotic neurons to block selected protein synthesis. This indicates that this type of vector is a good alternative to viral vectors to achieve very high transfection levels in neurons. This also suggests that carbosilane dendrimers might be very useful for gene therapy.
Journal of Cultural Heritage
Nowadays, some virtual museums include 3D room scenes to show the models of its pieces, just like... more Nowadays, some virtual museums include 3D room scenes to show the models of its pieces, just like in real museums. Nevertheless, the generation and maintenance of this kind of scenes is generally difficult and should be done by an expert. For example, any change such as including a new piece or modifying the position of an existing fragment usually requires
Journal of Micromechanics and Microengineering, 2005
... 08034 Barcelona, Spain 2 Laboratorio de Optoelectrónica, ´Area de Cargas ´Utiles e Instrument... more ... 08034 Barcelona, Spain 2 Laboratorio de Optoelectrónica, ´Area de Cargas ´Utiles e Instrumentación, Departamento de Ciencias del Espacio y Tecnologıas Electrónicas, Instituto de Técnica Aeroespacial (INTA) 28850 Torrejón de Ardoz, Madrid, Spain E-mail: sandra@eel. ...
Gastroenterology, 2010
Recibido el 11 de mayo de 2010; aceptado el 5 de agosto de 2010 Disponible en Internet el 3 de no... more Recibido el 11 de mayo de 2010; aceptado el 5 de agosto de 2010 Disponible en Internet el 3 de noviembre de 2010 PALABRAS CLAVE Enfermedad inflamatoria intestinal; Incidencia; Epidemiología; Inmigración
Journal of Critical Care, 2006
Purpose: The aim of the study was to identify early risk factors for development of acute respira... more Purpose: The aim of the study was to identify early risk factors for development of acute respiratory distress syndrome (ARDS) in severe trauma patients. Materials and Methods: This was a prospective observational study of 693 severe trauma patients (Injury Severity Score z16 and/or Revised Trauma Score V11) in 17 hospitals in a Spanish region of 8 million inhabitants from July 2002 to December 2002. Results: Acute respiratory distress syndrome developed in 6.9% of patients who were more severely ill with higher APACHE II ( P b .001) and Injury Severity Score ( P = .002) scores vs patients not developing ARDS. Acute respiratory distress syndrome development was associated ( P b .001) with fractures of femur (International Classification of Diseases, Ninth Revision [ICD-9] codes 820, 821), tibia (ICD-9 code 823), humerus, and pelvis, with a number (z2) of long bone fractures, and with chest injuries (rib/sternal fracture [ICD-9 code 807] and hemo/pneumothorax [ICD-9 code 860/861]). Patients with ARDS required more colloids ( P = .005) and red blood cell units ( P = .02) than patients without ARDS during the first 24 hours. Multivariate analysis showed that ARDS was related to chest trauma diagnosis (ICD-9 code 807) (odds ratio [OR], 3.85), femoral fracture (OR, 3.16), APACHE II score (OR, 1.05), and blood transfusion during resuscitation (OR, 1.32). Conclusions: Risk of ARDS development is related to the first 24-hour admission variables, including severe physiologic derangements and specific ICD-9-classified injuries. Blood transfusion may play an independent role. D
OBJETIVO: Determinar la utilidad de la ecografía con contraste en la detección de hipervasculariz... more OBJETIVO: Determinar la utilidad de la ecografía con contraste en la detección de hipervascularización arterial como criterio diagnóstico de carcinoma hepatocelular (CHC) en lesiones ocupantes de espacio (LOE) de pacientes con hepatopatía. PACIENTES Y MÉTODOS: Estudio prospectivo en el que se incluyen pacientes con hepatopatía crónica a los que se detectó alguna LOE mediante ecografía. Como potenciador se administró un contraste de segunda generación (SonoVue ® ). Se utilizó un ecógrafo Hitachi EUB 6500 con un programa específico para potenciadores, y se empleó un índice mecánico inferior a 0,14. Se analizó el patrón de captación en fase arterial, clasificándose en patrón difuso (homogéneo o heterogéneo), periférico, captación similar al parénquima circundante y ausencia de captación. El diagnóstico definitivo se confirmó mediante el estudio combinado de tomografía computarizada, resonancia magnética y análisis histológico, junto con la evolución clínica. RESULTADOS: Se incluyen 23 lesiones en 22 pacientes (uno presentó 2 lesiones de características ecográficas diferentes). El diagnóstico final fue: CHC en 12 casos, lesiones benignas en 9, metástasis en uno y colangiocarcinoma en otro caso. Todos los casos que presentaron un patrón difuso con el contraste tenían una lesión maligna, y los 8 casos con patrón difuso homogéneo tenían un CHC. El 75% de los pacientes con CHC presentó una hipervascularización arterial con un patrón difuso tras el contraste. Este patrón difuso presentó una sensibilidad del 71,4%, especificidad del 100%, valor predictivo positivo (VPP) del 100%, valor predictivo negativo (VPN) del 69,2% y exactitud del 82,6% para el diagnóstico de malignidad. El patrón difuso homogéneo presentó una sensibilidad del 66,7%, una especificidad del 100%, un VPP del 100%, un VPN del 73,3% y una exactitud del 82,6% para el diagnóstico de CHC. CONCLUSIONES: La utilización de la ecografía con contraste de segunda generación facilita una caracterización vascular inmediata de la lesión. En nuestro estudio se detecta una hipervascularización arterial en el 75% de los pacientes con CHC. Un patrón de realce difuso homogéneo es muy específico de CHC. Creemos que la detección de este tipo de patrón en un paciente con cirrosis haría innecesaria la utilización de más pruebas de imagen para el diagnóstico, si bien el estudio de extensión debe completarse con otra técnica.
Atmospheric Chemistry and Physics, 2006
A Markov Chain Monte Carlo model for integrating the observations of inorganic species with a the... more A Markov Chain Monte Carlo model for integrating the observations of inorganic species with a thermodynamic equilibrium model was presented in Part I of this series. Using observations taken at three ground sites, i.e. a residential, industrial and rural site, during the MCMA-2003 campaign in Mexico City, the model is used to an-5 alyze the inorganic aerosol and ammonia data and predict gas phase concentrations of nitric and hydrochloric acid. In general the model is able to accurately predict the observed inorganic aerosol concentrations at all three sites. The agreement between the predicted and observed gas phase ammonia concentration is excellent. The NO z concentration calculated from the NO y , NO and NO 2 observations is of limited use in 10 constraining the gas phase nitric acid concentration given the large uncertainties in this measure of nitric acid and additional reactive nitrogen species. Focusing on the acidic period of 9-11 April identified by Salcedo et al. (2006), the model accurately predicts the aerosol phase observations during this period with the exception of the nitrate predictions after 10:00 a.m. (CDT) on 9 April, where the model underpredicts 15 the observations by, on average, 20%. For periods when the aerosol chloride observations are consistently above the detection limit, the model is able to both accurately predict the aerosol chloride predictions and provide well-constrained HCl(g) concentrations. When the aerosols are aqueous, the most likely concentrations of HCl(g) are in the sub-ppbv range. The most likely predicted concentration of HCl(g) was found to 20 reach concentrations of order 10 ppbv if the aerosols are dry. Finally, the atmospheric relevance of HCl(g) is discussed in terms of its indicator properties for the possible influence of chlorine-mediated photochemistry in Mexico City.
Un tema que debe interesar al profesorado de Matemáticas de todos los niveles educativos es cómo ... more Un tema que debe interesar al profesorado de Matemáticas de todos los niveles educativos es cómo hacer comprender a nuestros alumnos la utilidad de los conceptos matemáticos que están estudiando en nuestras asignaturas. Si se les presenta aplicaciones de las Matemáticas en temas atractivos e interesantes conseguiremos motivar a nuestros alumnos. Una de estas aplicaciones es el cifrado de la información.
Biodrugs, 2010
Background: HIV infection of the CNS is the principle cause of HIV-associated dementia in adults ... more Background: HIV infection of the CNS is the principle cause of HIV-associated dementia in adults and encephalopathy in children. Gene therapy techniques such as small interfering RNA (siRNA) possess great potential in drug development, but first they must overcome the key obstacle of reaching the interior of the affected cells. A successful delivery vector for anti-HIV drugs that is capable of crossing the blood-brain barrier (BBB) could provide a way of addressing this issue. Non-viral vectors such as dendrimers offer a means for effectively delivering and transfecting siRNA to the target cells. Objective: To evaluate the application of gene therapy for reducing HIV replication in human astrocytes. Methods: We used the 2G-NN16 amino-terminated carbosilane dendrimer as a method for delivering siRNA to HIV-infected human astrocytes. We tested the cytotoxicity in human astrocytoma cells caused by 2G-NN16 and dendriplexes formed with siRNA (siRNA 2G-NN16) by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium-bromide (MTT) and lactate dehydrogenase assays. The ability to transfect human astrocytes with siRNA 2G-NN16 dendriplexes was tested by flow cytometry and immunofluorescence microscopy. To assess the potential capability of siRNA 2G-NN16 dendriplexes for crossing the BBB, we used an in vitro transcytosis assay with bovine brain microvascular endothelial cells. HIV-1 inhibition assays using 2G-NN16 and siRNA 2G-NN16 dendriplexes were determined by quantification of the viral load from culture supernatants of the astrocytes. Results: A gradual time-controlled degradation of the 2G-NN16 dendrimer and liberation of its siRNA cargo between 12 and 24 hours was observed via gel electrophoresis. There was no cytotoxicity in HIVinfected or non-infected human astrocytoma cells when treated with up to 24 mg mL of 2G-NN16 dendrimer or siRNA 2G-NN16 dendriplexes, and siRNA 2G-NN16 dendriplexes were seen to successfully transfect human astrocytes even after crossing an in vitro BBB model. More interestingly, transfected siRNA was observed to exert a biologic effect, as dendriplexes were shown to down-regulate the housekeeping gene GAPDH and to reduce replication of HIV-1 strains X4-HIV NL4-3 and R5-HIV BaL in human astrocytes. Conclusions: The 2G-NN16 dendrimer successfully delivers and transfects siRNA to HIV-infected human astrocytes and achieves gene silencing without causing cytotoxicity.
Pharmaceutical Research, 2009
Purpose To study the effect of a non-viral vector (carbosilane dendrimer) to efficiently deliver ... more Purpose To study the effect of a non-viral vector (carbosilane dendrimer) to efficiently deliver small interfering RNA to postmitotic neurons to study the function of hypoxia-inducible factor-1α (HIF1-α) during chemical hypoxia-mediated neurotoxicity. Methods Chemical hypoxia was induced in primary rat cortical neurons by exposure to CoCl2. HIF1-α levels were determined by Western Blot and toxicity was evaluated by both MTT and LDH assays. Neurons were incubated with dendriplexes containing anti-HIF1-α siRNA and both uptake and HIF1-α knockdown efficiency were evaluated. Results We report that a non-viral vector (carbosilane dendrimer) can deliver specific siRNA to neurons and selectively block HIF1-α synthesis with similar efficiency to that achieved by viral vectors. Using this method, we have found that this transcription factor plays a neuroprotective role during the early phase of chemical hypoxia-mediated neurotoxicity. Conclusion This work represents a proof-of-concept for the use of carbosilane dendrimers to deliver specific siRNA to postmitotic neurons to block selected protein synthesis. This indicates that this type of vector is a good alternative to viral vectors to achieve very high transfection levels in neurons. This also suggests that carbosilane dendrimers might be very useful for gene therapy.
Journal of Cultural Heritage
Nowadays, some virtual museums include 3D room scenes to show the models of its pieces, just like... more Nowadays, some virtual museums include 3D room scenes to show the models of its pieces, just like in real museums. Nevertheless, the generation and maintenance of this kind of scenes is generally difficult and should be done by an expert. For example, any change such as including a new piece or modifying the position of an existing fragment usually requires
Journal of Micromechanics and Microengineering, 2005
... 08034 Barcelona, Spain 2 Laboratorio de Optoelectrónica, ´Area de Cargas ´Utiles e Instrument... more ... 08034 Barcelona, Spain 2 Laboratorio de Optoelectrónica, ´Area de Cargas ´Utiles e Instrumentación, Departamento de Ciencias del Espacio y Tecnologıas Electrónicas, Instituto de Técnica Aeroespacial (INTA) 28850 Torrejón de Ardoz, Madrid, Spain E-mail: sandra@eel. ...
Gastroenterology, 2010
Recibido el 11 de mayo de 2010; aceptado el 5 de agosto de 2010 Disponible en Internet el 3 de no... more Recibido el 11 de mayo de 2010; aceptado el 5 de agosto de 2010 Disponible en Internet el 3 de noviembre de 2010 PALABRAS CLAVE Enfermedad inflamatoria intestinal; Incidencia; Epidemiología; Inmigración
Journal of Critical Care, 2006
Purpose: The aim of the study was to identify early risk factors for development of acute respira... more Purpose: The aim of the study was to identify early risk factors for development of acute respiratory distress syndrome (ARDS) in severe trauma patients. Materials and Methods: This was a prospective observational study of 693 severe trauma patients (Injury Severity Score z16 and/or Revised Trauma Score V11) in 17 hospitals in a Spanish region of 8 million inhabitants from July 2002 to December 2002. Results: Acute respiratory distress syndrome developed in 6.9% of patients who were more severely ill with higher APACHE II ( P b .001) and Injury Severity Score ( P = .002) scores vs patients not developing ARDS. Acute respiratory distress syndrome development was associated ( P b .001) with fractures of femur (International Classification of Diseases, Ninth Revision [ICD-9] codes 820, 821), tibia (ICD-9 code 823), humerus, and pelvis, with a number (z2) of long bone fractures, and with chest injuries (rib/sternal fracture [ICD-9 code 807] and hemo/pneumothorax [ICD-9 code 860/861]). Patients with ARDS required more colloids ( P = .005) and red blood cell units ( P = .02) than patients without ARDS during the first 24 hours. Multivariate analysis showed that ARDS was related to chest trauma diagnosis (ICD-9 code 807) (odds ratio [OR], 3.85), femoral fracture (OR, 3.16), APACHE II score (OR, 1.05), and blood transfusion during resuscitation (OR, 1.32). Conclusions: Risk of ARDS development is related to the first 24-hour admission variables, including severe physiologic derangements and specific ICD-9-classified injuries. Blood transfusion may play an independent role. D
OBJETIVO: Determinar la utilidad de la ecografía con contraste en la detección de hipervasculariz... more OBJETIVO: Determinar la utilidad de la ecografía con contraste en la detección de hipervascularización arterial como criterio diagnóstico de carcinoma hepatocelular (CHC) en lesiones ocupantes de espacio (LOE) de pacientes con hepatopatía. PACIENTES Y MÉTODOS: Estudio prospectivo en el que se incluyen pacientes con hepatopatía crónica a los que se detectó alguna LOE mediante ecografía. Como potenciador se administró un contraste de segunda generación (SonoVue ® ). Se utilizó un ecógrafo Hitachi EUB 6500 con un programa específico para potenciadores, y se empleó un índice mecánico inferior a 0,14. Se analizó el patrón de captación en fase arterial, clasificándose en patrón difuso (homogéneo o heterogéneo), periférico, captación similar al parénquima circundante y ausencia de captación. El diagnóstico definitivo se confirmó mediante el estudio combinado de tomografía computarizada, resonancia magnética y análisis histológico, junto con la evolución clínica. RESULTADOS: Se incluyen 23 lesiones en 22 pacientes (uno presentó 2 lesiones de características ecográficas diferentes). El diagnóstico final fue: CHC en 12 casos, lesiones benignas en 9, metástasis en uno y colangiocarcinoma en otro caso. Todos los casos que presentaron un patrón difuso con el contraste tenían una lesión maligna, y los 8 casos con patrón difuso homogéneo tenían un CHC. El 75% de los pacientes con CHC presentó una hipervascularización arterial con un patrón difuso tras el contraste. Este patrón difuso presentó una sensibilidad del 71,4%, especificidad del 100%, valor predictivo positivo (VPP) del 100%, valor predictivo negativo (VPN) del 69,2% y exactitud del 82,6% para el diagnóstico de malignidad. El patrón difuso homogéneo presentó una sensibilidad del 66,7%, una especificidad del 100%, un VPP del 100%, un VPN del 73,3% y una exactitud del 82,6% para el diagnóstico de CHC. CONCLUSIONES: La utilización de la ecografía con contraste de segunda generación facilita una caracterización vascular inmediata de la lesión. En nuestro estudio se detecta una hipervascularización arterial en el 75% de los pacientes con CHC. Un patrón de realce difuso homogéneo es muy específico de CHC. Creemos que la detección de este tipo de patrón en un paciente con cirrosis haría innecesaria la utilización de más pruebas de imagen para el diagnóstico, si bien el estudio de extensión debe completarse con otra técnica.
Atmospheric Chemistry and Physics, 2006
A Markov Chain Monte Carlo model for integrating the observations of inorganic species with a the... more A Markov Chain Monte Carlo model for integrating the observations of inorganic species with a thermodynamic equilibrium model was presented in Part I of this series. Using observations taken at three ground sites, i.e. a residential, industrial and rural site, during the MCMA-2003 campaign in Mexico City, the model is used to an-5 alyze the inorganic aerosol and ammonia data and predict gas phase concentrations of nitric and hydrochloric acid. In general the model is able to accurately predict the observed inorganic aerosol concentrations at all three sites. The agreement between the predicted and observed gas phase ammonia concentration is excellent. The NO z concentration calculated from the NO y , NO and NO 2 observations is of limited use in 10 constraining the gas phase nitric acid concentration given the large uncertainties in this measure of nitric acid and additional reactive nitrogen species. Focusing on the acidic period of 9-11 April identified by Salcedo et al. (2006), the model accurately predicts the aerosol phase observations during this period with the exception of the nitrate predictions after 10:00 a.m. (CDT) on 9 April, where the model underpredicts 15 the observations by, on average, 20%. For periods when the aerosol chloride observations are consistently above the detection limit, the model is able to both accurately predict the aerosol chloride predictions and provide well-constrained HCl(g) concentrations. When the aerosols are aqueous, the most likely concentrations of HCl(g) are in the sub-ppbv range. The most likely predicted concentration of HCl(g) was found to 20 reach concentrations of order 10 ppbv if the aerosols are dry. Finally, the atmospheric relevance of HCl(g) is discussed in terms of its indicator properties for the possible influence of chlorine-mediated photochemistry in Mexico City.
Un tema que debe interesar al profesorado de Matemáticas de todos los niveles educativos es cómo ... more Un tema que debe interesar al profesorado de Matemáticas de todos los niveles educativos es cómo hacer comprender a nuestros alumnos la utilidad de los conceptos matemáticos que están estudiando en nuestras asignaturas. Si se les presenta aplicaciones de las Matemáticas en temas atractivos e interesantes conseguiremos motivar a nuestros alumnos. Una de estas aplicaciones es el cifrado de la información.