ABSTRACT
Pulmonary arterial hypertension (PAH) is a life-threatening disease that is characterized by an increase in pulmonary vascular pressure, leading to ventricular failure and high morbidity and mortality. Resveratrol, a phenolic compound and a sirtuin 1 pathway activator, has known dietary benefits and is used as a treatment for anti-inflammatory and cardiovascular diseases. Its therapeutic effects have been published in the scientific literature; however, its benefits in PAH are yet to be precisely elucidated. Using a murine model of PAH induced by monocrotaline, the macroscopic and microscopic effects of a daily oral dose of resveratrol in rats with PAH were evaluated by determining its impact on the lungs and the right and left ventricular function. While most literature has focused on smooth muscle cell mechanisms and lung pathology, our results highlight the relevance of therapy-mediated improvement of right ventricle and isolated cardiomyocyte physiology in both ventricles. Although significant differences in the pulmonary architecture were not identified either micro- or macroscopically, the effects of resveratrol on right ventricular function and remodeling were observed to be beneficial. The values for the volume, diameter, and contractility of the right ventricular cardiomyocytes returned to those of the control group, suggesting that resveratrol has a protective effect against ventricular dysfunction and pathological remodeling changes in PAH. The effect of resveratrol in the right ventricle delayed the progression of findings associated with right heart failure and had a limited positive effect on the architecture of the lungs. The use of resveratrol could be considered a future potential adjunct therapy, especially when the challenges to making a diagnosis and the current therapy limitations for PAH are taken into consideration.
Subject(s)
Antioxidants/therapeutic use , Echocardiography/methods , Lung/pathology , Pulmonary Arterial Hypertension/prevention & control , Resveratrol/therapeutic use , Ventricular Remodeling/drug effects , Animals , Antioxidants/pharmacology , Disease Models, Animal , Male , Rats , Rats, Sprague-Dawley , Resveratrol/pharmacologyABSTRACT
Background: Thyroid hormone status in hypothyroidism (HT) downregulates key elements in Ca2+ handling within the heart, reducing contractility, impairing the basal energetic balance, and increasing the risk of cardiovascular disease. Mitochondrial Ca2+ transport is reduced in HT, and tolerance to reperfusion damage has been documented, but the precise mechanism is not well understood. Therefore, we aimed to determine the stoichiometry and activity of the mitochondrial Ca2+ uniporter or uniplex in an HT model and the relevance to the opening of the mitochondrial permeability transition pores (mPTP) during ischemia/reperfusion (I/R) injury. Methods: An HT model was established in Wistar rats by treatment with 6-propylthiouracil for 28 days. Uniplex composition and activity were determined in cardiac mitochondria. Hearts were perfused ex vivo to induce I/R injury, and functional parameters related to contractility and tissue viability were evaluated. Results: The cardiac stoichiometry between two subunits of the uniplex (MICU1/MCU) increased by 25% in animals with HT. The intramitochondrial Ca2+ content was reduced by 40% and was less prone to the mPTP opening. After I/R injury, ischemic contracture and the onset of ventricular fibrillation were delayed in animals with HT, concomitant with a reduction in oxidative damage and mitochondrial dysfunction. Conclusions: Our results suggest that HT is associated with an increase in the cardiac MICU1/MCU ratio, thereby changing the stoichiometry between these subunits to increase the threshold to cytosolic Ca2+ and reduce mitochondrial Ca2+ overload. Our results also demonstrate that this HT model can be used to explore the role of mitochondrial Ca2+ transport in cardiac diseases due to its induced tolerance to cardiac damage.
Subject(s)
Calcium/metabolism , Hypothyroidism/metabolism , Hypothyroidism/physiopathology , Mitochondria, Heart/metabolism , Myocardial Reperfusion Injury/physiopathology , Animals , Antithyroid Agents , Cytosol/metabolism , Hypothyroidism/chemically induced , Male , Mitochondrial Membrane Transport Proteins , Mitochondrial Permeability Transition Pore , Oxidative Stress , Propylthiouracil , Rats , Rats, Wistar , Ventricular Fibrillation/etiology , Ventricular Fibrillation/physiopathologyABSTRACT
O livro reúne os trabalhos do encontro Jornadas Temáticas, ocorrido na França em março de 1998. Organizada e dirigida por Edgar Morin, tem como tema os desafios que o conhecimento irá enfrentar no novo milênio: conjugar os conhecimentos em torno dos problemas essenciais da humanidade e lidar com a fragmentação dos saberes, compartimentados em disciplinas diversas e inseridos em múltiplas realidades.
Subject(s)
Humans , Education , Philosophy , Adolescent , Art , DNA , Earth, Planet , Environmental Imbalance , Environment , Heredity , LongevityABSTRACT
Este libro presenta algunas de las conjunciones, descentramientos, coincidencias y disyunciones entre paradigmas científicos, estéticos, culturales y terapéuticos con los que nos acercamos al siglo XXI. Propone entender estos desarrollos de la cultura contemporánea como procesos generativos inmersos en una historia sociocultural y una subjetividad transversal a las que, a su vez, ellos configuran. Aspira a contribuir a la apertura de futuros científicos, culturales y terapéuticos y al reconocimiento de los procesos emergentes, de la multiplicidad y la diversidad
ABSTRACT
Este libro presenta algunas de las conjunciones, descentramientos, coincidencias y disyunciones entre paradigmas científicos, estéticos, culturales y terapéuticos con los que nos acercamos al siglo XXI. Propone entender estos desarrollos de la cultura contemporánea como procesos generativos inmersos en una historia sociocultural y una subjetividad transversal a las que, a su vez, ellos configuran. Aspira a contribuir a la apertura de futuros científicos, culturales y terapéuticos y al reconocimiento de los procesos emergentes, de la multiplicidad y la diversidad
ABSTRACT
Preocupa y alarma el poderío potencial de los medios de comunicación. Pero hay otra base, probablemente más realista para la generalizada preocupación por la función social, una base que se vincula con los cambiantes tipos de control social ejercitados por poderosos grupos de interés. Los trabajos incluídos en la presente obra fueron seleccionados por er especialmente representativos de las diversas tendencias, amén de inteligentes, perspicaces, desprejuiciados y audaces
ABSTRACT
Preocupa y alarma el poderío potencial de los medios de comunicación. Pero hay otra base, probablemente más realista para la generalizada preocupación por la función social, una base que se vincula con los cambiantes tipos de control social ejercitados por poderosos grupos de interés. Los trabajos incluídos en la presente obra fueron seleccionados por er especialmente representativos de las diversas tendencias, amén de inteligentes, perspicaces, desprejuiciados y audaces
