Metformin intervention prevents cardiac dysfunction in a murine model of adult congenital heart disease

OBJECTIVE: Congenital heart disease (CHD) is the most frequent birth defect worldwide. The number of adult patients with CHD, now referred to as ACHD, is increasing with improved surgical and treatment interventions. However the mechanisms whereby ACHD predisposes patients to heart dysfunction are still unclear. ACHD is strongly associated with metabolic syndrome, but how ACHD interacts with poor modern lifestyle choices and other comorbidities, such as hypertension, obesity, and diabetes, is mostly unknown. METHODS: We used a newly characterized mouse genetic model of ACHD to investigate the consequences and the mechanisms associated with combined obesity and ACHD predisposition. Metformin intervention was used to further evaluate potential therapeutic amelioration of cardiac dysfunction in this model. RESULTS: ACHD mice placed under metabolic stress (high fat diet) displayed decreased left ventricular ejection fraction. Comprehensive physiological, biochemical, and molecular analysis showed that ACHD hearts exhibited early changes in energy metabolism with increased glucose dependence as main cardiac energy source. These changes preceded cardiac dysfunction mediated by exposure to high fat diet and were associated with increased disease severity. Restoration of metabolic balance by metformin administration prevented the development of heart dysfunction in ACHD predisposed mice. CONCLUSIONS: This study reveals that early metabolic impairment reinforces heart dysfunction in ACHD predisposed individuals and diet or pharmacological interventions can be used to modulate heart function and attenuate heart failure. Our study suggests that interactions between genetic and metabolic disturbances ultimately lead to the clinical presentation of heart failure in patients with ACHD. Early manipulation of energy metabolism may be an important avenue for intervention in ACHD patients to prevent or delay onset of heart failure and secondary comorbidities. These interactions raise the prospect for a translational reassessment of ACHD presentation in the clinic

An item response theory model for students ability evaluation using computer-automated test results

The aim of this paper is to evaluate the student learning about Computer Science subjects. A questionnaire based on ordinal scored items has been submitted to the students through a computer automated system. The data collected have been analyzed by using a latent variable model for ordinal data within the Item Response Theory framework. The scores obtained from the model allow to classify the students according to the reached competence

Influencia de la enfermedad periodontal en la evaluación de los trastornos funcionales digestivos

Fil: LASA, J. S. Centro de Educación Médica e Investigación Clínica Norberto Quirno. Departamento de Medicina Interna. Sección de Gastroenterología; Argentina.Fil: DIMA, G. Centro de Educación Médica e Investigación Clínica Norberto Quirno. Departamento de Medicina Interna. Sección de Gastroenterología; Argentina.Fil: PERALTA, A. D. Centro de Educación Médica e Investigación Clínica Norberto Quirno. Departamento de Medicina Interna. Sección de Gastroenterología; Argentina.Fil: CAGNONE, G. Universidad de Buenos Aires. Facultad de Odontología. Cátedra de Clínica II de Operatoria y Prótesis; Argentina.Fil: SOIFER, L. O. Centro de Educación Médica e Investigación Clínica Norberto Quirno. Departamento de Medicina Interna. Sección de Gastroenterología; Argentina.Existe evidencias de una asociación entre las alteraciones de la flora bacteriana intestinal y el síndrome de intestino irritable (SII). Dichas alteraciones pueden ser medidas en forma indirecta mediante el test de hidrógeno en aire espirado con lactulosa (THAEL). La flora bacteriana puede verse también alterada en sujetos con enfermedad periodontal (EP). Objetivo: Evaluar la influencia de la EP sobre los resultados del THAEL

The adenosine salvage pathway as an alternative to mitochondrial production of ATP in maturing mammalian oocytes

Although the oocyte is the largest cell in the body and an unavoidable phase in life, its physiology is still poorly understood, and other cell types provide little insight into its unique nature. Even basic cellular functions in the oocyte such as energy metabolism are not yet fully understood. It is known that the mitochondria of the female gamete exhibit an immature form characterized by limited energy production from glucose and oxidative phosphorylation. We show that the bovine oocyte uses alternative means to maintain ATP production during maturation, namely, the adenosine salvage pathway. Meiosis resumption is triggered by destruction of cyclic AMP by phosphodiesterases producing adenosine monophosphate that is converted into ATP by adenylate kinases and creatine kinases. Inhibition of these enzymes decreased ATP production, and addition of their substrates restored ATP production in denuded oocytes. Addition of phosphocreatine to the oocyte maturation medium influenced the phenotype of the resulting blastocysts. We propose a model in which adenylate kinases and creatine kinases act as drivers of ATP production from added AMP during oocyte maturation

The adenosine salvage pathway as an alternative to mitochondrial production of ATP in maturing mammalian oocytes

Mitochondria in maturing oocytes and early embryos change shape from the usual mature form seen in other cells to an immature form that has very limited capacity for energy production from glucose and oxidative phosphorylation (OXPHOS). With the high demand for energy in these cells and limited capacity for OXPHOS, it is unclear how these cells meet their energy needs. This study provides evidence that a previously unexplored potential driver of ATP synthesis, the adenosine salvage pathway, can meet the energy needs of growing bovine oocytes. Considerable amounts of adenosine monophosphate (AMP) become available at the onset of maturation trough the destruction of cyclic AMP by phosphodiesterases which triggers resumption of meiosis. The conversion of AMP to ADP and then to ATP occurs through the action of 2 enzymes. The first of these, adenylate kinase, catalyzes the conversion of AMP to ADP; the second, creatine kinase, converts ADP to ATP. Adding inhibitors of these enzymes to the oocyte maturation medium decreased ATP production; adding their substrates to denuded oocytes restored ATP production. Adding phosphocreatine alone also restored ATP levels substantially and influenced the phenotype of the resulting blastocysts, improving embryo quality and yield. The use of the adenosine salvage pathway explains how growing oocytes with limited ability to generate ATP through traditional OXPHOS pathways can meet energy requirements