Mario Cañas Navarro - Academia.edu (original) (raw)

Papers by Mario Cañas Navarro

Research paper thumbnail of La estructura de competencia partidaria Argentina: análisis y evaluación de la imagen analítica de la «territorialización» del sistema de partidos

Revista Chilena de Derecho y Ciencia Política

Este ensayo analiza la tesis de la “territorialización” de la política en Argentina a través del ... more Este ensayo analiza la tesis de la “territorialización” de la política en Argentina a través del examen detallado de una de sus principales hipótesis: la imagen de una fragmentación partidaria regionalmente desequilibrada. Establecidas las principales apuestas empíricas de la tesis de la FRD -fragmentación regionalmente desequilibrada-, se procede a examinar su validez empírica y se concluye que la hipótesis de la “territorialización” tiene sólo un apoyo parcial en los datos. Se finaliza interpretando estos resultados como la necesidad de explorar más detenidamente una previa imagen del funcionamiento del sistema de partidos del país, imagen aquí denominada “clásica”.

Research paper thumbnail of Manual: Elementos verticales interiores (III), Tipos Constructivos

Research paper thumbnail of Proceedings of the VII Nereus International Workshop : "Clitic Doubling and other issues of the syntax/semantic interface in Romance DPs

The aim of this paper is to highlight the relation between Clitic Doubling constructions (CLD) an... more The aim of this paper is to highlight the relation between Clitic Doubling constructions (CLD) and leísmo in Spanish. In order to do this, we show that whether a language allows CLD or not does not depend on whether a dialect allows leísmo or not, but on the kind of features encoded in the clitic itself. More specifically, CLD of object DPs depends on the number and internal organization of the features that the dative clitic encodes. Thus, we will argue that there is a strong correlation between the markedness of the clitic pronoun and the restrictions clitic doubling underlies. In this paper, we will propose a Feature Geometry (cf. Harley & Ritter 1998 and Heap 2005) representing the hierarchical organization of the features which is able to account for the restrictions that are attested concerning the occurrence of CLD in these varieties.

Research paper thumbnail of Caspase selective reagents for diagnosing apoptotic mechanisms

Cell death and differentiation, Jan 10, 2018

Apical caspases initiate and effector caspases execute apoptosis. Reagents that can distinguish b... more Apical caspases initiate and effector caspases execute apoptosis. Reagents that can distinguish between caspases, particularly apical caspases-8, 9, and 10 are scarce and generally nonspecific. Based upon a previously described large-scale screen of peptide-based caspase substrates termed HyCoSuL, we sought to develop reagents to distinguish between apical caspases in order to reveal their function in apoptotic cell death paradigms. To this end, we selected tetrapeptide-based sequences that deliver optimal substrate selectivity and converted them to inhibitors equipped with a detectable tag (activity-based probes-ABPs). We demonstrate a strong relationship between substrate kinetics and ABP kinetics. To evaluate the utility of selective substrates and ABPs, we examined distinct apoptosis pathways in Jurkat T lymphocyte and MDA-MB-231 breast cancer lines triggered to undergo cell death via extrinsic or intrinsic apoptosis. We report the first highly selective substrate appropriate fo...

Research paper thumbnail of Reparación del cistocele por vía vaginal con malla subvesical sin tensión: técnica y resultados

Research paper thumbnail of Análisis de los proteomas de dos micoplasmas: Mycoplasma penetrans y Mycoplasma genitalium

Research paper thumbnail of Propuesta para la sistematización de la atención en el síndrome doloroso subacromial

Revista Mexicana De Ortopedia Y Traumatologia, Aug 1, 1999

Research paper thumbnail of Luxación posterior glenohumeral. Informe de tres casos

Revista Mexicana De Ortopedia Y Traumatologia, 1999

Research paper thumbnail of Tratamiento quirúrgico de la inestabilidad glenohumeral multidireccional

Revista Mexicana De Ortopedia Y Traumatologia, Aug 1, 1999

Research paper thumbnail of Iatrogenia negativa en cirugía del hombro

Revista Mexicana De Ortopedia Y Traumatologia, 1999

Research paper thumbnail of The caspase-8 inhibitor emricasan combines with the SMAC mimetic birinapant to induce necroptosis and treat acute myeloid leukemia

Science translational medicine, May 18, 2016

Resistance to chemotherapy is a major problem in cancer treatment, and it is frequently associate... more Resistance to chemotherapy is a major problem in cancer treatment, and it is frequently associated with failure of tumor cells to undergo apoptosis. Birinapant, a clinical SMAC mimetic, had been designed to mimic the interaction between inhibitor of apoptosis proteins (IAPs) and SMAC/Diablo, thereby relieving IAP-mediated caspase inhibition and promoting apoptosis of cancer cells. We show that acute myeloid leukemia (AML) cells are sensitive to birinapant-induced death and that the clinical caspase inhibitor emricasan/IDN-6556 augments, rather than prevents, killing by birinapant. Deletion of caspase-8 sensitized AML to birinapant, whereas combined loss of caspase-8 and the necroptosis effector MLKL (mixed lineage kinase domain-like) prevented birinapant/IDN-6556-induced death, showing that inhibition of caspase-8 sensitizes AML cells to birinapant-induced necroptosis. However, loss of MLKL alone did not prevent a caspase-dependent birinapant/IDN-6556-induced death, implying that AM...

Research paper thumbnail of La imagen de una fragmentación partidaria con desequilibrio regional en la política argentina. Una revisión analítica

Ciencia Politica, Nov 15, 2012

El presente artículo se propone revisar analíticamente una imagen sumamente influyente para expli... more El presente artículo se propone revisar analíticamente una imagen sumamente influyente para explicar el proceso político-partidario argentino, imagen que denominamos "fragmentación partidaria con desequilibrio regional" (FDR). La FDR evoca un proceso de "territorialización", entendido como una suerte de descentramiento de las fuerzas partidarias que multiplica centros de gravitación política en áreas subnacionales. De acuerdo a esta imagen, el sistema de partidos argentino sufre de un desajuste en su estructura de competencia puesto que, junto a una creciente fragmentación partidaria en áreas centrales, tendría lugar una compresión de la competencia partidaria en las demás áreas o provincias periféricas. En el presente trabajo se testean las principales teorías que sostienen esta imagen, a saber: la descentralización del gasto, la devaluación de etiquetas partidarias, la transfiguración de la cultura política y un efecto mecánico provocado por la magnitud de los distritos. Una revisión detallada a estas explicaciones demuestra que, si bien se trata de procesos gravitantes y con una clara tendencia a tomar mayor intensidad, no explican el carácter y trayectoria de la "territorialización" de la política en Argentina.

Research paper thumbnail of Cervicoartrosis: efectividad de un tratamiento fisioterápico convencional

Revista De Fisioterapia, Jul 1, 2005

espanolEl objetivo de este estudio consiste en valorar la efectividad de un tratamiento de fisiot... more espanolEl objetivo de este estudio consiste en valorar la efectividad de un tratamiento de fisioterapia convencional para la cervicoartrosis (microondas, traccion cervical, movilizacion activa, masaje e higiene postural). Para su realizacion, se han seleccionado 32 pacientes (26 mujeres y 6 hombres) diagnosticados de cervicoartrosis. Se han valorado factores como el dolor y el balance articular. Tras analizar los resultados, concluimos que el tratamiento planteado es efectivo en la patologia de artrosis cervical. EnglishThe aim of this study is to see the effectiveness of a classic physiotherapy treatment for the cervical joint degeneration (microwaves, cervical traction, active mobilisation, massage and ergonomy). For the study 32 patients was selectioned (26 women and 6 men), all with cervical joint degeneration diagnosis. Pain and cervical mobility is evaluated. After results analysis, the conclusion of the study is that the physiotherapy treatment proposed is effective.

Research paper thumbnail of Apoptosis Activation in Human Lung Cancer Cell Lines by a Novel Synthetic Peptide Derived from Conus californicus Venom

Toxins, 2016

Lung cancer is one of the most common types of cancer in men and women and a leading cause of dea... more Lung cancer is one of the most common types of cancer in men and women and a leading cause of death worldwide resulting in more than one million deaths per year. The venom of marine snails Conus contains up to 200 pharmacologically active compounds that target several receptors in the cell membrane. Due to their diversity and specific binding properties, Conus toxins hold great potential as source of new drugs against cancer. We analyzed the cytotoxic effect of a 17-amino acid synthetic peptide (s-cal14.1a) that is based on a native toxin (cal14.1a) isolated from the sea snail Conus californicus. Cytotoxicity studies in four lung cancer cell lines were complemented with measurement of gene expression of apoptosis-related proteins Bcl-2, BAX and the pro-survival proteins NFκB-1 and COX-2, as well as quantification of caspase activity. Our results showed that H1299 and H1437 cell lines treated with s-call4.1a had decreased cell viability, activated caspases, and reduced expression of the pro-survival protein NFκB-1. To our knowledge, this is the first report describing activation of apoptosis in human lung cancer cell lines by s-cal14.1a and we offer insight into the possible mechanism of action.

Research paper thumbnail of ¿Por qué es única la Península de BC?

Research paper thumbnail of Niveles aumentados de estrés oxidativo se asocian a disfunción endotelial periférica y respuesta vascular pulmonar disminuida frente a vasodilatadores en pacientes con hipertensión pulmonar

Revista chilena de cardiología, 2010

Research paper thumbnail of Metabolismo energético del corazón y sus proyecciones en el tratamiento de la insuficiencia cardíaca

Revista médica de Chile, 2010

Heart energy metabolism and its role in the treatment of heart failure It is unknown why heart fa... more Heart energy metabolism and its role in the treatment of heart failure It is unknown why heart failure progresses even when patients are treated with the best therapy available. Evidences suggest that heart failure progression is due to loss of neurohumoral blockade in advanced stages of the disease and to alterations in myocardial metabolism induced, in part, by this neurohumoral activation. Alterations in cardiac energy metabolism, especially those related to substrate utilization and insulin resistance, reduce the efficiency of energy production, causing a heart energy reserve deficit. These events play a basic role in heart failure progression. Therefore, modulation of cardiac metabolism has arisen as a promissory therapy in the treatment of heart failure. This review describes myocardial energy metabolism, evaluates the role of impaired energy metabolism in heart failure progression and describes new therapies for heart failure involving metabolic intervention.

Research paper thumbnail of EsiB, a Novel Pathogenic Escherichia coli Secretory Immunoglobulin A-Binding Protein Impairing Neutrophil Activation

mBio, 2013

In this study, we have characterized the functional properties of a novel Escherichia coli antige... more In this study, we have characterized the functional properties of a novel Escherichia coli antigen named EsiB ( E . coli s ecretory i mmunoglobulin A- b inding protein), recently reported to protect mice from sepsis. Gene distribution analysis of a panel of 267 strains representative of different E. coli pathotypes revealed that esiB is preferentially associated with extraintestinal strains, while the gene is rarely found in either intestinal or nonpathogenic strains. These findings were supported by the presence of anti-EsiB antibodies in the sera of patients affected by urinary tract infections (UTIs). By solving its crystal structure, we observed that EsiB adopts a superhelical fold composed of Sel1-like repeats (SLRs), a feature often associated with bacterial proteins possessing immunomodulatory functions. Indeed, we found that EsiB interacts with secretory immunoglobulin A (SIgA) through a specific motif identified by an immunocapturing approach. Functional assays showed that ...

Research paper thumbnail of Xanthine-oxidase inhibitors and statins in chronic heart failure: Effects on vascular and functional parameters

The Journal of Heart and Lung Transplantation, 2011

BACKGROUND: Increased oxidative stress in heart failure (HF) leads to inflammation and endothelia... more BACKGROUND: Increased oxidative stress in heart failure (HF) leads to inflammation and endothelial dysfunction (ED). Both statins and allopurinol have known anti-oxidant properties, but their utility in HF has not been fully assessed. METHODS: This investigation was a prospective, double-blind, double-dummy study, performed between March 2007 and June 2009. Seventy-four HF patients, with New York Heart Association (NYHA) Class II or III status and left ventricular ejection fraction (LVEF) Ͻ40%, were included. Patients received placebo during 4 weeks and were then randomized to receive 4 weeks of either atorvastatin 20 mg/day plus placebo (ATVϩPLA group) or atorvastatin 20 mg/day orally plus allopurinol 300 mg/day orally (ATVϩALLO group). Malondialdehyde (MDA), extracellular superoxide dismutase (ecSOD) activity and uric acid (UA) levels, among others, were determined at baseline and after 4 weeks of treatment. ED was assessed by flow-dependent endothelial-mediated vasodilation (FDD), and functional capacity by 6-minute walk test (6MWT). RESULTS: Thirty-two patients were randomized to ATVϩPLA and 38 to ATVϩALLO. Mean age was 59 Ϯ 2 years, 82% were male, and 22% had an ischemic etiology. Hypertension was present in 60% and diabetes in 15% of those studied. No significant differences were observed between baseline measurements and after placebo. After 4 weeks of treatment, both groups showed a significant decrease on MDA (0.9 Ϯ 0.1 to 0.8 Ϯ 0.1 and 1.0 Ϯ 0.5 to 0.9 Ϯ 0.1 mol/liter, p ϭ 0.88), UA (7.4 Ϯ 0.4 to 6.8 Ϯ 0.3 and 7.2 Ϯ 0.4 to 5.0 Ϯ 0.3 mg/dl, p Ͻ 0.01) and FDD (3.9 Ϯ 0.2% to 5.6 Ϯ 0.4% and 4.6 Ϯ 0.3% to 7.1 Ϯ 0.5%, p ϭ 0.07) with increased ecSOD activity (109 Ϯ 11 to 173 Ϯ 13 and 98 Ϯ 10 to 202 Ϯ 16, U/ml/min, p ϭ 0.41) and improved 6MWT (447 Ϯ 18 to 487 Ϯ 19 and 438 Ϯ 17 to 481 Ϯ 21 m, p ϭ 0.83), with all values for ATVϩPLA and ATVϩALLO, respectively; p-values are for comparison between groups after treatment. CONCLUSION: Short-term ATV treatment in heart failure (HF) patients reduces oxidative stress and improves FDD and functional capacity. These beneficial effects are not strenghthened by the addition of alopurinol.

Research paper thumbnail of Systemic Oxidative Stress and Endothelial Dysfunction is Associated With an Attenuated Acute Vascular Response to Inhaled Prostanoid in Pulmonary Artery Hypertension Patients

Journal of Cardiac Failure, 2011

Systemic endothelial dysfunction and increased oxidative stress have been observed in pulmonary a... more Systemic endothelial dysfunction and increased oxidative stress have been observed in pulmonary arterial hypertension (PAH). We evaluate whether oxidative stress and endothelial dysfunction are associated with acute pulmonary vascular bed response to an inhaled prostanoid in PAH patients. Fourteen idiopathic PAH patients and 14 controls were included. Oxidative stress was assessed through plasma malondialdehyde (MDA) levels and xanthine oxidase (XO) and endothelial-bound superoxide dismutase (eSOD) activity. Brachial artery endothelial-dependent flow-mediated vasodilation (FMD) was used to evaluate endothelial function. Hemodynamic response to inhaled iloprost was assessed with transthoracic echocardiography. PAH patients showed impaired FMD (2.8 ± 0.6 vs. 10.7 ± 0.6%, P < .01), increased MDA levels and XO activity (0.6 ± 0.2 vs. 0.3 ± 0.2 μM, P < .01 and 0.04 ± 0.01 vs. 0.03 ± 0.01 U/mL, P = .02, respectively) and decreased eSOD activity (235 ± 23 vs. 461 ± 33 AUC, P…

Research paper thumbnail of La estructura de competencia partidaria Argentina: análisis y evaluación de la imagen analítica de la «territorialización» del sistema de partidos

Revista Chilena de Derecho y Ciencia Política

Este ensayo analiza la tesis de la “territorialización” de la política en Argentina a través del ... more Este ensayo analiza la tesis de la “territorialización” de la política en Argentina a través del examen detallado de una de sus principales hipótesis: la imagen de una fragmentación partidaria regionalmente desequilibrada. Establecidas las principales apuestas empíricas de la tesis de la FRD -fragmentación regionalmente desequilibrada-, se procede a examinar su validez empírica y se concluye que la hipótesis de la “territorialización” tiene sólo un apoyo parcial en los datos. Se finaliza interpretando estos resultados como la necesidad de explorar más detenidamente una previa imagen del funcionamiento del sistema de partidos del país, imagen aquí denominada “clásica”.

Research paper thumbnail of Manual: Elementos verticales interiores (III), Tipos Constructivos

Research paper thumbnail of Proceedings of the VII Nereus International Workshop : "Clitic Doubling and other issues of the syntax/semantic interface in Romance DPs

The aim of this paper is to highlight the relation between Clitic Doubling constructions (CLD) an... more The aim of this paper is to highlight the relation between Clitic Doubling constructions (CLD) and leísmo in Spanish. In order to do this, we show that whether a language allows CLD or not does not depend on whether a dialect allows leísmo or not, but on the kind of features encoded in the clitic itself. More specifically, CLD of object DPs depends on the number and internal organization of the features that the dative clitic encodes. Thus, we will argue that there is a strong correlation between the markedness of the clitic pronoun and the restrictions clitic doubling underlies. In this paper, we will propose a Feature Geometry (cf. Harley & Ritter 1998 and Heap 2005) representing the hierarchical organization of the features which is able to account for the restrictions that are attested concerning the occurrence of CLD in these varieties.

Research paper thumbnail of Caspase selective reagents for diagnosing apoptotic mechanisms

Cell death and differentiation, Jan 10, 2018

Apical caspases initiate and effector caspases execute apoptosis. Reagents that can distinguish b... more Apical caspases initiate and effector caspases execute apoptosis. Reagents that can distinguish between caspases, particularly apical caspases-8, 9, and 10 are scarce and generally nonspecific. Based upon a previously described large-scale screen of peptide-based caspase substrates termed HyCoSuL, we sought to develop reagents to distinguish between apical caspases in order to reveal their function in apoptotic cell death paradigms. To this end, we selected tetrapeptide-based sequences that deliver optimal substrate selectivity and converted them to inhibitors equipped with a detectable tag (activity-based probes-ABPs). We demonstrate a strong relationship between substrate kinetics and ABP kinetics. To evaluate the utility of selective substrates and ABPs, we examined distinct apoptosis pathways in Jurkat T lymphocyte and MDA-MB-231 breast cancer lines triggered to undergo cell death via extrinsic or intrinsic apoptosis. We report the first highly selective substrate appropriate fo...

Research paper thumbnail of Reparación del cistocele por vía vaginal con malla subvesical sin tensión: técnica y resultados

Research paper thumbnail of Análisis de los proteomas de dos micoplasmas: Mycoplasma penetrans y Mycoplasma genitalium

Research paper thumbnail of Propuesta para la sistematización de la atención en el síndrome doloroso subacromial

Revista Mexicana De Ortopedia Y Traumatologia, Aug 1, 1999

Research paper thumbnail of Luxación posterior glenohumeral. Informe de tres casos

Revista Mexicana De Ortopedia Y Traumatologia, 1999

Research paper thumbnail of Tratamiento quirúrgico de la inestabilidad glenohumeral multidireccional

Revista Mexicana De Ortopedia Y Traumatologia, Aug 1, 1999

Research paper thumbnail of Iatrogenia negativa en cirugía del hombro

Revista Mexicana De Ortopedia Y Traumatologia, 1999

Research paper thumbnail of The caspase-8 inhibitor emricasan combines with the SMAC mimetic birinapant to induce necroptosis and treat acute myeloid leukemia

Science translational medicine, May 18, 2016

Resistance to chemotherapy is a major problem in cancer treatment, and it is frequently associate... more Resistance to chemotherapy is a major problem in cancer treatment, and it is frequently associated with failure of tumor cells to undergo apoptosis. Birinapant, a clinical SMAC mimetic, had been designed to mimic the interaction between inhibitor of apoptosis proteins (IAPs) and SMAC/Diablo, thereby relieving IAP-mediated caspase inhibition and promoting apoptosis of cancer cells. We show that acute myeloid leukemia (AML) cells are sensitive to birinapant-induced death and that the clinical caspase inhibitor emricasan/IDN-6556 augments, rather than prevents, killing by birinapant. Deletion of caspase-8 sensitized AML to birinapant, whereas combined loss of caspase-8 and the necroptosis effector MLKL (mixed lineage kinase domain-like) prevented birinapant/IDN-6556-induced death, showing that inhibition of caspase-8 sensitizes AML cells to birinapant-induced necroptosis. However, loss of MLKL alone did not prevent a caspase-dependent birinapant/IDN-6556-induced death, implying that AM...

Research paper thumbnail of La imagen de una fragmentación partidaria con desequilibrio regional en la política argentina. Una revisión analítica

Ciencia Politica, Nov 15, 2012

El presente artículo se propone revisar analíticamente una imagen sumamente influyente para expli... more El presente artículo se propone revisar analíticamente una imagen sumamente influyente para explicar el proceso político-partidario argentino, imagen que denominamos "fragmentación partidaria con desequilibrio regional" (FDR). La FDR evoca un proceso de "territorialización", entendido como una suerte de descentramiento de las fuerzas partidarias que multiplica centros de gravitación política en áreas subnacionales. De acuerdo a esta imagen, el sistema de partidos argentino sufre de un desajuste en su estructura de competencia puesto que, junto a una creciente fragmentación partidaria en áreas centrales, tendría lugar una compresión de la competencia partidaria en las demás áreas o provincias periféricas. En el presente trabajo se testean las principales teorías que sostienen esta imagen, a saber: la descentralización del gasto, la devaluación de etiquetas partidarias, la transfiguración de la cultura política y un efecto mecánico provocado por la magnitud de los distritos. Una revisión detallada a estas explicaciones demuestra que, si bien se trata de procesos gravitantes y con una clara tendencia a tomar mayor intensidad, no explican el carácter y trayectoria de la "territorialización" de la política en Argentina.

Research paper thumbnail of Cervicoartrosis: efectividad de un tratamiento fisioterápico convencional

Revista De Fisioterapia, Jul 1, 2005

espanolEl objetivo de este estudio consiste en valorar la efectividad de un tratamiento de fisiot... more espanolEl objetivo de este estudio consiste en valorar la efectividad de un tratamiento de fisioterapia convencional para la cervicoartrosis (microondas, traccion cervical, movilizacion activa, masaje e higiene postural). Para su realizacion, se han seleccionado 32 pacientes (26 mujeres y 6 hombres) diagnosticados de cervicoartrosis. Se han valorado factores como el dolor y el balance articular. Tras analizar los resultados, concluimos que el tratamiento planteado es efectivo en la patologia de artrosis cervical. EnglishThe aim of this study is to see the effectiveness of a classic physiotherapy treatment for the cervical joint degeneration (microwaves, cervical traction, active mobilisation, massage and ergonomy). For the study 32 patients was selectioned (26 women and 6 men), all with cervical joint degeneration diagnosis. Pain and cervical mobility is evaluated. After results analysis, the conclusion of the study is that the physiotherapy treatment proposed is effective.

Research paper thumbnail of Apoptosis Activation in Human Lung Cancer Cell Lines by a Novel Synthetic Peptide Derived from Conus californicus Venom

Toxins, 2016

Lung cancer is one of the most common types of cancer in men and women and a leading cause of dea... more Lung cancer is one of the most common types of cancer in men and women and a leading cause of death worldwide resulting in more than one million deaths per year. The venom of marine snails Conus contains up to 200 pharmacologically active compounds that target several receptors in the cell membrane. Due to their diversity and specific binding properties, Conus toxins hold great potential as source of new drugs against cancer. We analyzed the cytotoxic effect of a 17-amino acid synthetic peptide (s-cal14.1a) that is based on a native toxin (cal14.1a) isolated from the sea snail Conus californicus. Cytotoxicity studies in four lung cancer cell lines were complemented with measurement of gene expression of apoptosis-related proteins Bcl-2, BAX and the pro-survival proteins NFκB-1 and COX-2, as well as quantification of caspase activity. Our results showed that H1299 and H1437 cell lines treated with s-call4.1a had decreased cell viability, activated caspases, and reduced expression of the pro-survival protein NFκB-1. To our knowledge, this is the first report describing activation of apoptosis in human lung cancer cell lines by s-cal14.1a and we offer insight into the possible mechanism of action.

Research paper thumbnail of ¿Por qué es única la Península de BC?

Research paper thumbnail of Niveles aumentados de estrés oxidativo se asocian a disfunción endotelial periférica y respuesta vascular pulmonar disminuida frente a vasodilatadores en pacientes con hipertensión pulmonar

Revista chilena de cardiología, 2010

Research paper thumbnail of Metabolismo energético del corazón y sus proyecciones en el tratamiento de la insuficiencia cardíaca

Revista médica de Chile, 2010

Heart energy metabolism and its role in the treatment of heart failure It is unknown why heart fa... more Heart energy metabolism and its role in the treatment of heart failure It is unknown why heart failure progresses even when patients are treated with the best therapy available. Evidences suggest that heart failure progression is due to loss of neurohumoral blockade in advanced stages of the disease and to alterations in myocardial metabolism induced, in part, by this neurohumoral activation. Alterations in cardiac energy metabolism, especially those related to substrate utilization and insulin resistance, reduce the efficiency of energy production, causing a heart energy reserve deficit. These events play a basic role in heart failure progression. Therefore, modulation of cardiac metabolism has arisen as a promissory therapy in the treatment of heart failure. This review describes myocardial energy metabolism, evaluates the role of impaired energy metabolism in heart failure progression and describes new therapies for heart failure involving metabolic intervention.

Research paper thumbnail of EsiB, a Novel Pathogenic Escherichia coli Secretory Immunoglobulin A-Binding Protein Impairing Neutrophil Activation

mBio, 2013

In this study, we have characterized the functional properties of a novel Escherichia coli antige... more In this study, we have characterized the functional properties of a novel Escherichia coli antigen named EsiB ( E . coli s ecretory i mmunoglobulin A- b inding protein), recently reported to protect mice from sepsis. Gene distribution analysis of a panel of 267 strains representative of different E. coli pathotypes revealed that esiB is preferentially associated with extraintestinal strains, while the gene is rarely found in either intestinal or nonpathogenic strains. These findings were supported by the presence of anti-EsiB antibodies in the sera of patients affected by urinary tract infections (UTIs). By solving its crystal structure, we observed that EsiB adopts a superhelical fold composed of Sel1-like repeats (SLRs), a feature often associated with bacterial proteins possessing immunomodulatory functions. Indeed, we found that EsiB interacts with secretory immunoglobulin A (SIgA) through a specific motif identified by an immunocapturing approach. Functional assays showed that ...

Research paper thumbnail of Xanthine-oxidase inhibitors and statins in chronic heart failure: Effects on vascular and functional parameters

The Journal of Heart and Lung Transplantation, 2011

BACKGROUND: Increased oxidative stress in heart failure (HF) leads to inflammation and endothelia... more BACKGROUND: Increased oxidative stress in heart failure (HF) leads to inflammation and endothelial dysfunction (ED). Both statins and allopurinol have known anti-oxidant properties, but their utility in HF has not been fully assessed. METHODS: This investigation was a prospective, double-blind, double-dummy study, performed between March 2007 and June 2009. Seventy-four HF patients, with New York Heart Association (NYHA) Class II or III status and left ventricular ejection fraction (LVEF) Ͻ40%, were included. Patients received placebo during 4 weeks and were then randomized to receive 4 weeks of either atorvastatin 20 mg/day plus placebo (ATVϩPLA group) or atorvastatin 20 mg/day orally plus allopurinol 300 mg/day orally (ATVϩALLO group). Malondialdehyde (MDA), extracellular superoxide dismutase (ecSOD) activity and uric acid (UA) levels, among others, were determined at baseline and after 4 weeks of treatment. ED was assessed by flow-dependent endothelial-mediated vasodilation (FDD), and functional capacity by 6-minute walk test (6MWT). RESULTS: Thirty-two patients were randomized to ATVϩPLA and 38 to ATVϩALLO. Mean age was 59 Ϯ 2 years, 82% were male, and 22% had an ischemic etiology. Hypertension was present in 60% and diabetes in 15% of those studied. No significant differences were observed between baseline measurements and after placebo. After 4 weeks of treatment, both groups showed a significant decrease on MDA (0.9 Ϯ 0.1 to 0.8 Ϯ 0.1 and 1.0 Ϯ 0.5 to 0.9 Ϯ 0.1 mol/liter, p ϭ 0.88), UA (7.4 Ϯ 0.4 to 6.8 Ϯ 0.3 and 7.2 Ϯ 0.4 to 5.0 Ϯ 0.3 mg/dl, p Ͻ 0.01) and FDD (3.9 Ϯ 0.2% to 5.6 Ϯ 0.4% and 4.6 Ϯ 0.3% to 7.1 Ϯ 0.5%, p ϭ 0.07) with increased ecSOD activity (109 Ϯ 11 to 173 Ϯ 13 and 98 Ϯ 10 to 202 Ϯ 16, U/ml/min, p ϭ 0.41) and improved 6MWT (447 Ϯ 18 to 487 Ϯ 19 and 438 Ϯ 17 to 481 Ϯ 21 m, p ϭ 0.83), with all values for ATVϩPLA and ATVϩALLO, respectively; p-values are for comparison between groups after treatment. CONCLUSION: Short-term ATV treatment in heart failure (HF) patients reduces oxidative stress and improves FDD and functional capacity. These beneficial effects are not strenghthened by the addition of alopurinol.

Research paper thumbnail of Systemic Oxidative Stress and Endothelial Dysfunction is Associated With an Attenuated Acute Vascular Response to Inhaled Prostanoid in Pulmonary Artery Hypertension Patients

Journal of Cardiac Failure, 2011

Systemic endothelial dysfunction and increased oxidative stress have been observed in pulmonary a... more Systemic endothelial dysfunction and increased oxidative stress have been observed in pulmonary arterial hypertension (PAH). We evaluate whether oxidative stress and endothelial dysfunction are associated with acute pulmonary vascular bed response to an inhaled prostanoid in PAH patients. Fourteen idiopathic PAH patients and 14 controls were included. Oxidative stress was assessed through plasma malondialdehyde (MDA) levels and xanthine oxidase (XO) and endothelial-bound superoxide dismutase (eSOD) activity. Brachial artery endothelial-dependent flow-mediated vasodilation (FMD) was used to evaluate endothelial function. Hemodynamic response to inhaled iloprost was assessed with transthoracic echocardiography. PAH patients showed impaired FMD (2.8 ± 0.6 vs. 10.7 ± 0.6%, P < .01), increased MDA levels and XO activity (0.6 ± 0.2 vs. 0.3 ± 0.2 μM, P < .01 and 0.04 ± 0.01 vs. 0.03 ± 0.01 U/mL, P = .02, respectively) and decreased eSOD activity (235 ± 23 vs. 461 ± 33 AUC, P…