Upregulation of the angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas receptor axis in the heart and the kidney of growth hormone receptor knock-out mice

Objective: Growth hormone (GH) resistance leads to enhanced insulin sensitivity, decreased systolic blood pressure and increased lifespan. The aim of this study was to determine if there is a shift in the balance of the renin-angiotensin system (RAS) towards the ACE2/Ang-(1-7)/Mas receptor axis in the heart and the kidney of a model of GH resistance and retarded aging, the GH receptor knockout (GHR. -/-) mouse. Design: RAS components were evaluated in the heart and the kidney of GHR -/- and control mice by immunohistochemistry and Western blotting (n = 12 for both groups). Results: The immunostaining of Ang-(1-7) was increased in both the heart and the kidney of GHR. -/- mice. These changes were concomitant with an increased immunostaining of the Mas receptor and ACE2 in both tissues. The immunostaining of AT1 receptor was reduced in heart and kidney of GHR -/- mice while that of AT2 receptor was increased in the heart and unaltered in the kidney. Ang II, ACE and angiotensinogen levels remained unaltered in the heart and the kidney of GH resistant mice. These results were confirmed by Western blotting and correlated with a significant increase in the abundance of the endothelial nitric oxide synthase in both tissues. Conclusions: The shift within the RAS towards an exacerbation of the ACE2/Ang-(1-7)/Mas receptor axis observed in GHR. -/- mice could be related to a protective role in cardiac and renal function; and thus, possibly contribute to the decreased incidence of cardiovascular diseases displayed by this animal model of longevity.Fil: Giani, Jorge Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Miquet, Johanna Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Muñoz, Marina Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Burghi, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Toblli, Jorge Eduardo. Hospital Aleman. Laboratorio de Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Masternak, Michal M.. University of Central Florida; Estados Unidos. Polish Academy of Sciences; ArgentinaFil: Kopchick, John J.. Ohio University; Estados UnidosFil: Bartke, Andrzej. Southern Illinois University; Estados UnidosFil: Turyn, Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Dominici, Fernando Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentin

Long-lived hypopituitary Ames dwarf mice are resistant to the detrimental effects of high-fat diet on metabolic function and energy expenditure

Growth hormone (GH) signaling stimulates the production of IGF-1; however, increased GH signaling may induce insulin resistance and can reduce life expectancy in both mice and humans. Interestingly, disruption of GH signaling by reducing plasma GH levels significantly improves health span and extends lifespan in mice, as observed in Ames dwarf mice. In addition, these mice have increased adiposity, yet are more insulin sensitive compared to control mice. Metabolic stressors such as high-fat diet (HFD) promote obesity and may alter longevity through the GH signaling pathway. Therefore, our objective was to investigate the effects of a HFD (metabolic stressor) on genetic mechanisms that regulate metabolism during aging. We show that Ames dwarf mice fed HFD for 12 weeks had an increase in subcutaneous and visceral adiposity as a result of diet-induced obesity, yet are more insulin sensitive and have higher levels of adiponectin compared to control mice fed HFD. Furthermore, energy expenditure was higher in Ames dwarf mice fed HFD than in control mice fed HFD. Additionally, we show that transplant of epididymal white adipose tissue (eWAT) from Ames dwarf mice fed HFD into control mice fed HFD improves their insulin sensitivity. We conclude that Ames dwarf mice are resistant to the detrimental metabolic effects of HFD and that visceral adipose tissue of Ames dwarf mice improves insulin sensitivity in control mice fed HFD.Fil: Hill, Cristal M.. Southern Illinois University; Estados UnidosFil: Fang, Yimin. Southern Illinois University; Estados UnidosFil: Miquet, Johanna Gabriela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Sun, Liou Y.. University of Alabama at Birmingahm; Estados UnidosFil: Masternak, Michal M.. University of Central Florida; Estados UnidosFil: Bartke, Andrzej. Southern Illinois University; Estados Unido

Toward Spin–Orbit Coupled Diabatic Potential Energy Surfaces for Methyl Iodide Using Effective Relativistic Coupling by Asymptotic Representation

The theoretical treatment of state–state interactions and the development of coupled multidimensional potential energy surfaces (PESs) is of fundamental importance for the theoretical investigation of nonadiabatic processes. Usually, only derivative or vibronic coupling is considered, but the presence of heavy atoms in a system can render spin–orbit (SO) coupling important as well. In the present study, we apply a new method recently developed by us (<i>J. Chem. Phys.</i> <b>2012</b>, <i>136</i>, 034103, and <i>J. Chem. Phys.</i> <b>2012</b>, <i>137</i>, 064101) to generate SO coupled diabatic PESs along the C–I dissociation coordinate for methyl iodide (CH₃I). This is the first and mandatory step toward the development of fully coupled full-dimensional PESs to describe the multistate photodynamics of this benchmark system. The method we use here is based on the diabatic asymptotic representation of the molecular fine structure states and an effective relativistic coupling operator. It therefore is called effective relativistic coupling by asymptotic representation (ERCAR). This approach allows the efficient and accurate generation of fully coupled PESs including derivative and SO coupling based on high-level <i>ab initio</i> calculations. In this study we develop a specific ERCAR model for CH₃I that so far accounts only for the C–I bond cleavage. Details of the diabatization and the accuracy of the results are investigated in comparison to reference <i>ab initio</i> calculations and experiments. The energies of the adiabatic fine structure states are reproduced in excellent agreement with <i>ab initio</i> SO–CI data. The model is also compared to available literature data, and its performance is evaluated critically. This shows that the new method is very promising for the construction of fully coupled full-dimensional PESs for CH₃I to be used in future quantum dynamics studies

Long-Lived Hypopituitary Ames Dwarf Mice Are Resistant To The Detrimental Effects Of High-Fat Diet On Metabolic Function And Energy Expenditure

Growth hormone (GH) signaling stimulates the production of IGF-1; however, increased GH signaling may induce insulin resistance and can reduce life expectancy in both mice and humans. Interestingly, disruption of GH signaling by reducing plasma GH levels significantly improves health span and extends lifespan in mice, as observed in Ames dwarf mice. In addition, these mice have increased adiposity, yet are more insulin sensitive compared to control mice. Metabolic stressors such as high-fat diet (HFD) promote obesity and may alter longevity through the GH signaling pathway. Therefore, our objective was to investigate the effects of a HFD (metabolic stressor) on genetic mechanisms that regulate metabolism during aging. We show that Ames dwarf mice fed HFD for 12 weeks had an increase in subcutaneous and visceral adiposity as a result of diet-induced obesity, yet are more insulin sensitive and have higher levels of adiponectin compared to control mice fed HFD. Furthermore, energy expenditure was higher in Ames dwarf mice fed HFD than in control mice fed HFD. Additionally, we show that transplant of epididymal white adipose tissue (eWAT) from Ames dwarf mice fed HFD into control mice fed HFD improves their insulin sensitivity. We conclude that Ames dwarf mice are resistant to the detrimental metabolic effects of HFD and that visceral adipose tissue of Ames dwarf mice improves insulin sensitivity in control mice fed HFD

Resistance To The Beneficial Metabolic Effects And Hepatic Antioxidant Defense Actions Of Fibroblast Growth Factor 21 Treatment In Growth Hormone-Overexpressing Transgenic Mice

Fibroblast growth factor 21 (FGF21) modulates a diverse range of biological functions, including glucose and lipid metabolism, adaptive starvation response, and energy homeostasis, but with limited mechanistic insight. FGF21 treatment has been shown to inhibit hepatic growth hormone (GH) intracellular signaling. To evaluate GH axis involvement in FGF21 actions, transgenic mice overexpressing bovine GH were used. Expectedly, in response to FGF21 treatment control littermates showed metabolic improvements whereas GH transgenic mice resisted most of the beneficial effects of FGF21, except an attenuation of the innate hyperinsulinemia. Since FGF21 is believed to exert its effects mostly at the transcriptional level, we analyzed and observed significant upregulation in expression of various genes involved in carbohydrate and lipid metabolism, energy homeostasis, and antioxidant defense in FGF21-treated controls, but not in GH transgenics. The resistance of GH transgenic mice to FGF21-induced changes underlines the necessity of normal GH signaling for the beneficial effects of FGF21

Estado de la provisión de cuidados nutricionales al paciente quemado: Auditoría de procesos en un Servicio de Quemados de un hospital terciario Current status of nutritional care provision to burnt patients: Processes audit of a burnt patients department from a tertiary hospital

Justificación: La respuesta al tratamiento médico-quirúrgico del paciente quemado pudiera depender tanto de los estragos provocados por la agresión térmica, a saber las demandas metabólicas incrementadas, la aparición del Síndrome de Respuesta Inflamatoria Sistémica, y las infecciones microbianas; como de las prácticas culturales incluidas dentro de los procesos institucionales de cuidados nutricionales. Objetivo: Evaluar cómo la conducción de los procesos nutricionales de evaluación e intervención influye sobre los indicadores de la efectividad terapéutica de los Servicios de Quemados. Serie de estudio: Cuarenta y dos pacientes atendidos con una superficie corporal quemada (SCQ) > 10%, entre enero del 2001-diciembre del 2003, en el Servicio de Quemados del Hospital Clínico Quirúrgico "Hermanos Ameijeiras" (Ciudad La Habana, Cuba). Métodos: Los procesos nutricionales de evaluación e intervención conducidos en el paciente quemado se auditaron mediante revisión de las historias clínicas. Los procesos auditados se declararon como Completados (o no). El grado de completamiento del proceso se relacionó con las tasas de complicaciones y mortalidad, y el índice de hospitalización predicho de la SCQ. Resultados: Los procesos nutricionales de evaluación e intervención se completaron en el 49,4% y 22,6% de las historias auditadas, respectivamente. El registro evolutivo del peso corporal se asoció con una menor mortalidad. La evaluación nutricional temprana y un aporte energético suficiente en lesionados con SCQ > 20% se asociaron con menores tasas de complicaciones y un mejor cumplimiento del índice de hospitalización. Conclusiones: Este trabajo constituye la primera aproximación al comportamiento del Servicio de Quemados de la institución, como antesala del diseño e implementación de un programa de mejoría continua de la calidad en la atención médica. Se pudo comprobar que, a pesar del estado actual de completamiento de los procesos nutricionales, la observancia de los mismos puede influir favorablemente sobre los indicadores de efectividad del Servicio.Rationale: Response of the burned patient to surgical medical treatment might depend not only upon the damages brought about by thermal agression, namely, increased metabolic requirements, onset of the Systemic Inflamatory Response Syndrome, and microbial infections, but also the cultural practices embedded within nutritional care institutional processes. Goal: To assess how conduction of nutritional care processes of assessment and intervention may influence therapeutical effectiveness indicators of hospital Burn Services. Study serie: Forty-two patients with a Burn Body Surface Area (BBSA) > 10% assisted at the Burn Service of the "Hermanos Ameijeiras" Clinical Surgical Hospital (La Habana, Cuba), between January 2001-December 2003. Methods: Nutritional care of assessment and intervention conducted upon the burn patient were audited after reviewing clinical charts. The audited processes were declared as Completed (or not). Completeness of the process was related to complications and mortality rates, and length of hospital stay predicted from BBSA. Results: Nutritional care processes of assessment and intervention were completed in 49.4% and 22.6% of the audited charts, respectively. Prospective recording of patient's body weight was associated with lower mortality. Early nutritional assessment and sufficient energy supply to patients with BBSA > 20% were associated with lower complications rates and better compliance with BBSA-predicted length of stay. Conclusions: This work is the first enquiry into the behaviour of the institution's Burn Service, in anticipation of the design and implementation of a medical care Continuous Quality Improvement Program. In spite of the current state of nutritional care processes completeness, their observance might favorably influence the Service's effectiveness indicators

High fidelity simulation and ECMO in intensive care unit. A multi profesionnal training program to improve skills and self efficacy

International audienc

Resistance to the Beneficial Metabolic Effects and Hepatic Antioxidant Defense Actions of Fibroblast Growth Factor 21 Treatment in Growth Hormone-Overexpressing Transgenic Mice

Fibroblast growth factor 21 (FGF21) modulates a diverse range of biological functions, including glucose and lipid metabolism, adaptive starvation response, and energy homeostasis, but with limited mechanistic insight. FGF21 treatment has been shown to inhibit hepatic growth hormone (GH) intracellular signaling. To evaluate GH axis involvement in FGF21 actions, transgenic mice overexpressing bovine GH were used. Expectedly, in response to FGF21 treatment control littermates showed metabolic improvements whereas GH transgenic mice resisted most of the beneficial effects of FGF21, except an attenuation of the innate hyperinsulinemia. Since FGF21 is believed to exert its effects mostly at the transcriptional level, we analyzed and observed significant upregulation in expression of various genes involved in carbohydrate and lipid metabolism, energy homeostasis, and antioxidant defense in FGF21-treated controls, but not in GH transgenics. The resistance of GH transgenic mice to FGF21-induced changes underlines the necessity of normal GH signaling for the beneficial effects of FGF21