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Papers by Guillermo Morales

Research paper thumbnail of La evaluación clínica de la terapia salina en el shock por quemaduras

Anales de la Facultad de Medicina, 2014

Este trabajo presenta algunos de los datos obtenidos durante los pasados tres años en el "Pe... more Este trabajo presenta algunos de los datos obtenidos durante los pasados tres años en el "Perú Project" sostenido por el Institute of Orthritis and Metabolic Diseases de los National Institutes of Health en Bethseda, Maryland, y algunos hospitales de caridad de Lima. El proyecto ha tenido como principal objetivo evaluar la eficacia de las soluciones ha tenido como principal objetivo evaluar la eficacia de las soluciones salinas administradas en grandes cantidades, principalmente por vía oral, como tratamiento de emergencia del shock en las quemaduras.

Research paper thumbnail of Association of high microvessel αvβ3 and low PTEN with poor outcome in stage 3 neuroblastoma: rationale for using first in class dual PI3K/BRD4 inhibitor, SF1126

Oncotarget, Jan 16, 2016

Neuroblastoma (NB) is the most common extracranial solid tumor in children. Our previous studies ... more Neuroblastoma (NB) is the most common extracranial solid tumor in children. Our previous studies showed that the angiogenic integrin αvβ3 was increased in high-risk metastatic (stage 4) NB compared with localized neuroblastomas. Herein, we show that integrin αvβ3 was expressed on 68% of microvessels in MYCN-amplified stage 3 neuroblastomas, but only on 34% (means) in MYCN-non-amplified tumors (p < 0.001; n = 54). PTEN, a tumor suppressor involved in αvβ3 signaling, was expressed in neuroblastomas either diffusely, focally or not at all (immunohistochemistry). Integrin αvβ3 was expressed on 60% of tumor microvessels when PTEN was negative or focal, as compared to 32% of microvessels in tumors with diffuse PTEN expression (p < 0.001). In a MYCN transgenic mouse model, loss of one allele of PTEN promoted tumor growth, illustrating the potential role of PTEN in neuroblastoma pathogenesis. Interestingly, we report the novel dual PI-3K/BRD4 activity of SF1126 (originally developed a...

Research paper thumbnail of An analog of camptothecin inactive against Topoisomerase I is broadly neutralizing of HIV-1 through inhibition of Vif-dependent APOBEC3G degradation

Antiviral Research, 2016

Camptothecin (CPT) is a natural product discovered to be active against various cancers through i... more Camptothecin (CPT) is a natural product discovered to be active against various cancers through its ability to inhibit Topoisomerase I (TOP1). CPT analogs also have anti-HIV-1 (HIV) activity that was previously shown to be independent of TOP1 inhibition. We show that a cancer inactive CPT analog (O2-16) inhibits HIV infection by disrupting multimerization of the HIV protein Vif. Antiviral activity depended on the expression of the cellular viral restriction factor APOBEC3G (A3G) that, in the absence of functional Vif, has the ability to hypermutate HIV proviral DNA during reverse transcription. Our studies demonstrate that O2-16 has low cytotoxicity and inhibits Vif-dependent A3G degradation, enabling A3G packaging into HIV viral particles that results in A3G signature hypermutations in viral genomes. This antiviral activity was A3G-dependent and broadly neutralizing against sixteen HIV clinical isolates from groups M (subtypes A-G), N, and O as well as seven single and multi-drug resistant strains of HIV. Molecular modeling predicted binding near the PPLP motif crucial for Vif multimerization and activity. O2-16 also was active in blocking Vif degradation of APOBEC3F (A3F). We propose that CPT analogs not active against TOP1 have novel therapeutic potential as Vif antagonists that enable A3G-dependent hypermutation of HIV.

Research paper thumbnail of Single agent and synergistic activity of the "first in class" dual PI3K/BRD4 inhibitor SF1126 with Sorafenib in hepatocellular carcinoma

Molecular cancer therapeutics, Nov 5, 2016

Deregulated PI3K/AKT/mTOR, Ras/Raf/MAPK and c-Myc signaling pathways are of prognostic significan... more Deregulated PI3K/AKT/mTOR, Ras/Raf/MAPK and c-Myc signaling pathways are of prognostic significance in hepatocellular carcinoma (HCC). Sorafenib, the only drug clinically approved for patients with advanced HCC, blocks the Ras/Raf/MAPK pathway but it does not inhibit the PI3K/AKT/mTOR pathway or c-Myc activation. Hence, there is an unmet medical need to identify potent PI-3K/BRD4 inhibitors which can be used either alone or in combination with Sorafenib to treat patients with advanced HCC. Herein we show that SF1126 (pan PI3K/BRD4 inhibitor) as single agent or in combination with Sorafenib inhibited proliferation, cell cycle, apoptosis and multiple key enzymes in PI3K/AKT/mTOR and Ras/Raf/MAPK pathway in Hep 3B, Hep G2, SK-Hep1 and Huh7 HCC cell lines. We demonstrate that the active moiety of the SF1126 prodrug, LY294002, binds to and blocks BRD4 interaction with the acetylated histone-H4 chromatin mark protein and displaced BRD4 co-activator protein from the transcriptional start s...

Research paper thumbnail of Abstract LB-211: A novel dual epigenetic/kinase inhibitory platform: SF2523 and analogues as first-in-class PI3K/BRD4 inhibitors

Cancer Research, 2016

The transcription factor MYC (c-MYC and MYCN) plays a key role in cancer but small molecule inhib... more The transcription factor MYC (c-MYC and MYCN) plays a key role in cancer but small molecule inhibitors of it have been elusive. A new series of PI3K inhibitors has been under investigation and through molecular modeling compounds have been designed to also inhibit the bromodomain protein BRD4. We used structure-based drug design to create a series of anticancer compounds based on a thieno-pyranone core that potently inhibit both the epigenetic regulator bromodomain protein BRD4 and the key nodal survival signaling kinase PI3K. Two lead dual PI3K/BRD4 inhibitors from our research are: pan-PI3K inhibitor SF2523 (PI3K alpha, beta, delta, gamma IC50 values in nM: 17, 214, 27, 232) inhibiting BRD4-1 and BRD4-2 (IC50 = 318 nM and 1660 nM), and delta-PI3K selective inhibitor SF2535 (PI3K alpha, beta, delta, gamma IC50 values in nM: 714, 1750, 27, 1170) inhibiting BRD4-1 and BRD4-2 (IC50 = 277 nM and 628 nM). Our results indicate that SF2523 blocks BRD4 binding to MYCN promoter PS1/PS2 using chromatin precipitation experiments. This approach provides for the first time access to inhibit the activity of MYC by enhancing its degradation (PI3K inhibition) and blocking MYC production via the inhibition of MYC transcription (BRD4 inhibition). Our studies demonstrate that SF2523 blocks M1-M2 transition and decreases levels of p-AKT, N-MYC in several neuroblastoma cell lines as well as in vivo simultaneous pharmacodynamic knockdown. Other in vivo studies show SF2523 blocks spontaneous metastasis and tumor growth. To date, SF2523 has demonstrated animal efficacy results without toxicity in the following 4 animal models: orthotopic pancreatic model, multiple myeloma model, renal cell carcinoma model, neuroblastoma xenograft model. The crystal structure of the dual PI3K/BRD4 inhibitor SF2523 with BRD4 has been determined providing key insights towards the design of more potent analogs. Our studies provide evidence that inhibition of PI3K-gamma and PI3K-delta by our thieno-pyranone chemotypes function as checkpoint inhibitors and enhance immune-therapeutics while BRD4 inhibition has been shown to block tumor-specific super-enhancers activating the innate and adaptive immune response providing a novel strategy to treat cancer. These dual inhibitors represent a new therapeutic approach inhibiting two key anticancer orthogonal mechanisms, BRD4 and PI3K, showing significant efficacy justifying further development efforts towards clinical evaluation. Citation Format: Alok Singh, Shweta Joshi, Joseph R. Garlich, Guillermo Morales, Tatiana Kutateladze, Forest Andrews, Donald Durden. A novel dual epigenetic/kinase inhibitory platform: SF2523 and analogues as first-in-class PI3K/BRD4 inhibitors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-211.

Research paper thumbnail of Control de mastitis bovina

Agricultura Revista Agropecuaria, 1998

Research paper thumbnail of Otitis media crónica superada en niños

Arch Argent Pediatr, Jun 1, 2004

Research paper thumbnail of Reporte de 5 casos de Edema Pulmonar Post-obstructivo, secundario a Laringoespasmo Post Extubación Anestésica, en el Hospital San Rafael de Alajuela

Revista Costarricense De Cardiologia, Apr 1, 2003

Research paper thumbnail of Determinación De Un Programa De Rehabilitación Social Orientado Al Desarrollo De Las Capacidades De Los Sentenciados Penalmente en El Centro De Rehabilitación Social De Varones De Guayaquil (CRSV-G), Como Una Iniciativa Para La Rehabilitación Integral

Research paper thumbnail of La poesía vanguardista en el aula de ELE

Research paper thumbnail of Analisis y Diseno De La Transmision Para Un Go Kart

Research paper thumbnail of A computational study of the structure of Dwork matrices

Eaca 2001 7 Encuentro De Algebra Computacional Y Aplicaciones Del 12 Al 14 De Septiembre De 2001 Ezcaray La Rioja 2001 Isbn 84 95301 52 0 Pags 149 153, 2001

Research paper thumbnail of Diabetes mellitus gestacional : análisis de incidencia, factores de riesgo y complicaciones, Hospital Militar Central, 2000-2005

Aim: To determine how has evolved the incidence of gestacional diabetes mellitus (GDM) at the Hos... more Aim: To determine how has evolved the incidence of gestacional diabetes mellitus (GDM) at the Hospital Militar central “Luis Arias Schreiber” (HMC) during the period 2000 - 2005, which are their risk factors and to determine the risk of complications. Method: A observational, descriptive, transversal, retrospective study design was used, in which all GDM new cases diagnosed between years 2000 and 2005 at the HMC were identified, soon to evaluate the magnitude of the associated risk to the knew risk factors as well as to evaluate the tendency and frequency distribution according to the year of study.

Research paper thumbnail of Cumplimiento del tratamiento farmacológico y control de la presión arterial en pacientes del programa de hipertensión: Hospital Víctor Lazarte Echegaray- EsSALUD, Trujillo

Revista Medica Herediana, 2013

Objetivo: Determinar si el tratamiento farmacologico es optimo en cumplimiento y en el control de... more Objetivo: Determinar si el tratamiento farmacologico es optimo en cumplimiento y en el control de los valores de presion arterial en los pacientes del Programa de Hipertension del Hospital Victor Lazarte Echegaray. Material y metodos: Se realizo un estudio transversal aleatorio en 81 pacientes en consultorio externo del programa. Resultados: 47 (58%) de los pacientes cumplen con las indicaciones y 58 (71.6%) de los pacientes acude regularmente a las citas. No encontramos relacion significativa entre cumplimiento y variables como grado de instruccion y el uso de monoterapia o asociaciones de antihipertensivos. Las razones para el incumplimiento senaladas por los pacientes fueron: No supo u olvido las recomendaciones (55.9%), se le agotaron los medicamentos que le suministra el programa (38.2%), sensacion de mejoria experimentada (2.9%) y efectos colaterales (2.9%). Cuarentaitres pacientes (53.8%) tuvieron controles de presion arterial adecuadas. Se encontro relacion significativa entre un control adecuado de presion arterial y el cumplimiento del tratamiento farmacologico antihipertensivo asi como con estadios I o II de hipertension arterial. Conclusiones: La principal razon senalada por los pacientes del incumplimiento del tratamiento fue el olvido de las indicaciones del medico. Se encontro relacion directa entre control adecuado de los niveles de presion arterial y cumplimiento del tratamiento asi como con estadios I o II de hipertension arterial. ( Rev Med Hered 2001; 12:120- 126).

Research paper thumbnail of Medidas cautelares: especial referencia a los centros de internamiento de extranjeros

Research paper thumbnail of Aplicación de los servicios de cobranza y asesoría prestados en la práctica mercantil salvadoreña a través del factoraje

Research paper thumbnail of Gerard Pierre-Carles: una semblanza

Revista Mexicana De Sociologia Vol 2005 No 002, Sep 14, 2011

Research paper thumbnail of Álgebra Para Ingeniería Química

Research paper thumbnail of Asymmetric syntheses and intermediates for preparing enantiomer-enriched hydroxyphosphinyl derivatives

Research paper thumbnail of Nuevos instrumentos para los nuevos desafíos del Ministerio Fiscal

Diario La Ley, 2013

El autor pretende contribuir al analisis de algunas de las propuestas de reforma que actualmente ... more El autor pretende contribuir al analisis de algunas de las propuestas de reforma que actualmente estan en marcha en el ambito de la Administracion de Justicia en general, y del Ministerio Fiscal en particular, y que seran objeto de estudio y debate en el proximo congreso de la Asociacion de Fiscales a celebrar los dias 26 y 27 de abril en Palma de Mallorca. En concreto, el Libro Blanco del Ministerio Fiscal y sus propuestas de redimensionamiento funcional de la institucion, un nuevo Estatuto Organico que refuerce su autonomia, y el Codigo Procesal Penal que apuesta decididamente por la atribucion de la investigacion penal al Ministerio Fiscal.

Research paper thumbnail of La evaluación clínica de la terapia salina en el shock por quemaduras

Anales de la Facultad de Medicina, 2014

Este trabajo presenta algunos de los datos obtenidos durante los pasados tres años en el "Pe... more Este trabajo presenta algunos de los datos obtenidos durante los pasados tres años en el "Perú Project" sostenido por el Institute of Orthritis and Metabolic Diseases de los National Institutes of Health en Bethseda, Maryland, y algunos hospitales de caridad de Lima. El proyecto ha tenido como principal objetivo evaluar la eficacia de las soluciones ha tenido como principal objetivo evaluar la eficacia de las soluciones salinas administradas en grandes cantidades, principalmente por vía oral, como tratamiento de emergencia del shock en las quemaduras.

Research paper thumbnail of Association of high microvessel αvβ3 and low PTEN with poor outcome in stage 3 neuroblastoma: rationale for using first in class dual PI3K/BRD4 inhibitor, SF1126

Oncotarget, Jan 16, 2016

Neuroblastoma (NB) is the most common extracranial solid tumor in children. Our previous studies ... more Neuroblastoma (NB) is the most common extracranial solid tumor in children. Our previous studies showed that the angiogenic integrin αvβ3 was increased in high-risk metastatic (stage 4) NB compared with localized neuroblastomas. Herein, we show that integrin αvβ3 was expressed on 68% of microvessels in MYCN-amplified stage 3 neuroblastomas, but only on 34% (means) in MYCN-non-amplified tumors (p < 0.001; n = 54). PTEN, a tumor suppressor involved in αvβ3 signaling, was expressed in neuroblastomas either diffusely, focally or not at all (immunohistochemistry). Integrin αvβ3 was expressed on 60% of tumor microvessels when PTEN was negative or focal, as compared to 32% of microvessels in tumors with diffuse PTEN expression (p < 0.001). In a MYCN transgenic mouse model, loss of one allele of PTEN promoted tumor growth, illustrating the potential role of PTEN in neuroblastoma pathogenesis. Interestingly, we report the novel dual PI-3K/BRD4 activity of SF1126 (originally developed a...

Research paper thumbnail of An analog of camptothecin inactive against Topoisomerase I is broadly neutralizing of HIV-1 through inhibition of Vif-dependent APOBEC3G degradation

Antiviral Research, 2016

Camptothecin (CPT) is a natural product discovered to be active against various cancers through i... more Camptothecin (CPT) is a natural product discovered to be active against various cancers through its ability to inhibit Topoisomerase I (TOP1). CPT analogs also have anti-HIV-1 (HIV) activity that was previously shown to be independent of TOP1 inhibition. We show that a cancer inactive CPT analog (O2-16) inhibits HIV infection by disrupting multimerization of the HIV protein Vif. Antiviral activity depended on the expression of the cellular viral restriction factor APOBEC3G (A3G) that, in the absence of functional Vif, has the ability to hypermutate HIV proviral DNA during reverse transcription. Our studies demonstrate that O2-16 has low cytotoxicity and inhibits Vif-dependent A3G degradation, enabling A3G packaging into HIV viral particles that results in A3G signature hypermutations in viral genomes. This antiviral activity was A3G-dependent and broadly neutralizing against sixteen HIV clinical isolates from groups M (subtypes A-G), N, and O as well as seven single and multi-drug resistant strains of HIV. Molecular modeling predicted binding near the PPLP motif crucial for Vif multimerization and activity. O2-16 also was active in blocking Vif degradation of APOBEC3F (A3F). We propose that CPT analogs not active against TOP1 have novel therapeutic potential as Vif antagonists that enable A3G-dependent hypermutation of HIV.

Research paper thumbnail of Single agent and synergistic activity of the "first in class" dual PI3K/BRD4 inhibitor SF1126 with Sorafenib in hepatocellular carcinoma

Molecular cancer therapeutics, Nov 5, 2016

Deregulated PI3K/AKT/mTOR, Ras/Raf/MAPK and c-Myc signaling pathways are of prognostic significan... more Deregulated PI3K/AKT/mTOR, Ras/Raf/MAPK and c-Myc signaling pathways are of prognostic significance in hepatocellular carcinoma (HCC). Sorafenib, the only drug clinically approved for patients with advanced HCC, blocks the Ras/Raf/MAPK pathway but it does not inhibit the PI3K/AKT/mTOR pathway or c-Myc activation. Hence, there is an unmet medical need to identify potent PI-3K/BRD4 inhibitors which can be used either alone or in combination with Sorafenib to treat patients with advanced HCC. Herein we show that SF1126 (pan PI3K/BRD4 inhibitor) as single agent or in combination with Sorafenib inhibited proliferation, cell cycle, apoptosis and multiple key enzymes in PI3K/AKT/mTOR and Ras/Raf/MAPK pathway in Hep 3B, Hep G2, SK-Hep1 and Huh7 HCC cell lines. We demonstrate that the active moiety of the SF1126 prodrug, LY294002, binds to and blocks BRD4 interaction with the acetylated histone-H4 chromatin mark protein and displaced BRD4 co-activator protein from the transcriptional start s...

Research paper thumbnail of Abstract LB-211: A novel dual epigenetic/kinase inhibitory platform: SF2523 and analogues as first-in-class PI3K/BRD4 inhibitors

Cancer Research, 2016

The transcription factor MYC (c-MYC and MYCN) plays a key role in cancer but small molecule inhib... more The transcription factor MYC (c-MYC and MYCN) plays a key role in cancer but small molecule inhibitors of it have been elusive. A new series of PI3K inhibitors has been under investigation and through molecular modeling compounds have been designed to also inhibit the bromodomain protein BRD4. We used structure-based drug design to create a series of anticancer compounds based on a thieno-pyranone core that potently inhibit both the epigenetic regulator bromodomain protein BRD4 and the key nodal survival signaling kinase PI3K. Two lead dual PI3K/BRD4 inhibitors from our research are: pan-PI3K inhibitor SF2523 (PI3K alpha, beta, delta, gamma IC50 values in nM: 17, 214, 27, 232) inhibiting BRD4-1 and BRD4-2 (IC50 = 318 nM and 1660 nM), and delta-PI3K selective inhibitor SF2535 (PI3K alpha, beta, delta, gamma IC50 values in nM: 714, 1750, 27, 1170) inhibiting BRD4-1 and BRD4-2 (IC50 = 277 nM and 628 nM). Our results indicate that SF2523 blocks BRD4 binding to MYCN promoter PS1/PS2 using chromatin precipitation experiments. This approach provides for the first time access to inhibit the activity of MYC by enhancing its degradation (PI3K inhibition) and blocking MYC production via the inhibition of MYC transcription (BRD4 inhibition). Our studies demonstrate that SF2523 blocks M1-M2 transition and decreases levels of p-AKT, N-MYC in several neuroblastoma cell lines as well as in vivo simultaneous pharmacodynamic knockdown. Other in vivo studies show SF2523 blocks spontaneous metastasis and tumor growth. To date, SF2523 has demonstrated animal efficacy results without toxicity in the following 4 animal models: orthotopic pancreatic model, multiple myeloma model, renal cell carcinoma model, neuroblastoma xenograft model. The crystal structure of the dual PI3K/BRD4 inhibitor SF2523 with BRD4 has been determined providing key insights towards the design of more potent analogs. Our studies provide evidence that inhibition of PI3K-gamma and PI3K-delta by our thieno-pyranone chemotypes function as checkpoint inhibitors and enhance immune-therapeutics while BRD4 inhibition has been shown to block tumor-specific super-enhancers activating the innate and adaptive immune response providing a novel strategy to treat cancer. These dual inhibitors represent a new therapeutic approach inhibiting two key anticancer orthogonal mechanisms, BRD4 and PI3K, showing significant efficacy justifying further development efforts towards clinical evaluation. Citation Format: Alok Singh, Shweta Joshi, Joseph R. Garlich, Guillermo Morales, Tatiana Kutateladze, Forest Andrews, Donald Durden. A novel dual epigenetic/kinase inhibitory platform: SF2523 and analogues as first-in-class PI3K/BRD4 inhibitors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-211.

Research paper thumbnail of Control de mastitis bovina

Agricultura Revista Agropecuaria, 1998

Research paper thumbnail of Otitis media crónica superada en niños

Arch Argent Pediatr, Jun 1, 2004

Research paper thumbnail of Reporte de 5 casos de Edema Pulmonar Post-obstructivo, secundario a Laringoespasmo Post Extubación Anestésica, en el Hospital San Rafael de Alajuela

Revista Costarricense De Cardiologia, Apr 1, 2003

Research paper thumbnail of Determinación De Un Programa De Rehabilitación Social Orientado Al Desarrollo De Las Capacidades De Los Sentenciados Penalmente en El Centro De Rehabilitación Social De Varones De Guayaquil (CRSV-G), Como Una Iniciativa Para La Rehabilitación Integral

Research paper thumbnail of La poesía vanguardista en el aula de ELE

Research paper thumbnail of Analisis y Diseno De La Transmision Para Un Go Kart

Research paper thumbnail of A computational study of the structure of Dwork matrices

Eaca 2001 7 Encuentro De Algebra Computacional Y Aplicaciones Del 12 Al 14 De Septiembre De 2001 Ezcaray La Rioja 2001 Isbn 84 95301 52 0 Pags 149 153, 2001

Research paper thumbnail of Diabetes mellitus gestacional : análisis de incidencia, factores de riesgo y complicaciones, Hospital Militar Central, 2000-2005

Aim: To determine how has evolved the incidence of gestacional diabetes mellitus (GDM) at the Hos... more Aim: To determine how has evolved the incidence of gestacional diabetes mellitus (GDM) at the Hospital Militar central “Luis Arias Schreiber” (HMC) during the period 2000 - 2005, which are their risk factors and to determine the risk of complications. Method: A observational, descriptive, transversal, retrospective study design was used, in which all GDM new cases diagnosed between years 2000 and 2005 at the HMC were identified, soon to evaluate the magnitude of the associated risk to the knew risk factors as well as to evaluate the tendency and frequency distribution according to the year of study.

Research paper thumbnail of Cumplimiento del tratamiento farmacológico y control de la presión arterial en pacientes del programa de hipertensión: Hospital Víctor Lazarte Echegaray- EsSALUD, Trujillo

Revista Medica Herediana, 2013

Objetivo: Determinar si el tratamiento farmacologico es optimo en cumplimiento y en el control de... more Objetivo: Determinar si el tratamiento farmacologico es optimo en cumplimiento y en el control de los valores de presion arterial en los pacientes del Programa de Hipertension del Hospital Victor Lazarte Echegaray. Material y metodos: Se realizo un estudio transversal aleatorio en 81 pacientes en consultorio externo del programa. Resultados: 47 (58%) de los pacientes cumplen con las indicaciones y 58 (71.6%) de los pacientes acude regularmente a las citas. No encontramos relacion significativa entre cumplimiento y variables como grado de instruccion y el uso de monoterapia o asociaciones de antihipertensivos. Las razones para el incumplimiento senaladas por los pacientes fueron: No supo u olvido las recomendaciones (55.9%), se le agotaron los medicamentos que le suministra el programa (38.2%), sensacion de mejoria experimentada (2.9%) y efectos colaterales (2.9%). Cuarentaitres pacientes (53.8%) tuvieron controles de presion arterial adecuadas. Se encontro relacion significativa entre un control adecuado de presion arterial y el cumplimiento del tratamiento farmacologico antihipertensivo asi como con estadios I o II de hipertension arterial. Conclusiones: La principal razon senalada por los pacientes del incumplimiento del tratamiento fue el olvido de las indicaciones del medico. Se encontro relacion directa entre control adecuado de los niveles de presion arterial y cumplimiento del tratamiento asi como con estadios I o II de hipertension arterial. ( Rev Med Hered 2001; 12:120- 126).

Research paper thumbnail of Medidas cautelares: especial referencia a los centros de internamiento de extranjeros

Research paper thumbnail of Aplicación de los servicios de cobranza y asesoría prestados en la práctica mercantil salvadoreña a través del factoraje

Research paper thumbnail of Gerard Pierre-Carles: una semblanza

Revista Mexicana De Sociologia Vol 2005 No 002, Sep 14, 2011

Research paper thumbnail of Álgebra Para Ingeniería Química

Research paper thumbnail of Asymmetric syntheses and intermediates for preparing enantiomer-enriched hydroxyphosphinyl derivatives

Research paper thumbnail of Nuevos instrumentos para los nuevos desafíos del Ministerio Fiscal

Diario La Ley, 2013

El autor pretende contribuir al analisis de algunas de las propuestas de reforma que actualmente ... more El autor pretende contribuir al analisis de algunas de las propuestas de reforma que actualmente estan en marcha en el ambito de la Administracion de Justicia en general, y del Ministerio Fiscal en particular, y que seran objeto de estudio y debate en el proximo congreso de la Asociacion de Fiscales a celebrar los dias 26 y 27 de abril en Palma de Mallorca. En concreto, el Libro Blanco del Ministerio Fiscal y sus propuestas de redimensionamiento funcional de la institucion, un nuevo Estatuto Organico que refuerce su autonomia, y el Codigo Procesal Penal que apuesta decididamente por la atribucion de la investigacion penal al Ministerio Fiscal.