Conocimientos de puérperas de un servicio de alojamiento conjunto sobre los signos y síntomas de alarma de las enfermedades en el recién nacido / Knowledge of puerperal women from a rooming-in on the warning signs and symptoms of diseases in the newborn

Introducción. La identificación de signos y síntomas de alarma en los recién nacidos permite la prevención de futuras complicaciones gracias a una rápida actuación médica. Objetivo. Describir los conocimientos de signos y síntomas de alarma de enfermedades del recién nacido en puérperas en el Servicio de Alojamiento Conjunto del Hospital Central de IPS. Metodología. Estudio observacional, descriptivo, prospectivo de corte transversal. Se encuestaron previo consentimiento informado a puérperas de sala de alojamiento conjunto, entre septiembre y octubre de 2021. Se analizaron las variables, edad, escolaridad, procedencia, número de hijos, 12 signos de alarma en recién nacidos. Los datos fueron analizados con SPSS v23, utilizando estadística descriptiva. Resultados. Participaron 125 puérperas entre 19 a 42 años (edad media: 28,9± 6 años) con escolaridad secundaria en el 54%. La paridad osciló entre 1 a 5 (mediana: 2) Los signos y síntomas de alarma más reconocidos fueron: las deposiciones sanguinolentas en un 90,4% (n=113), hipertonía de extremidades 89,6% (n=112), llanto persistente 81,6% (n=102), inapetencias tras 5 horas de alimentación 75,2% (n=94). En cuanto al desconocimiento el 72,8% (n=91) no conoce el valor de temperatura considerado como fiebre y el 56% (n=70) no reconoció la somnolencia como un signo de alarma inmediato. El 48% de las puérperas reconoció entre 7 a 8 signos y síntomas de alarmas. Conclusión. Las puérperas encuestadas tuvieron un nivel adecuado en el reconocimiento de los signos de alarma.

Introduction. The identification of alarm signs and symptoms in newborns allows the prevention of future complications thanks to rapid medical action. Objective. To describe the knowledge of warning signs and symptoms of diseases of the newborn in puerperal women in the rooming-in of the IPS Central Hospital. Methodology. An observational, descriptive, prospective cross-sectional study. After informed consent, puerperal women in a rooming-in between September and October 2021 were surveyed. The following variables were analyzed; age, education, residence, number of children, identification of 12 alarm signs in their newborns. The data were analyzed with SPSS v23, using descriptive statistics. Results. 125 puerperal women between 19 to 42 years (mean age: 28.9 ± 6 years) participated, with 54% secondary education. Parity ranged from 1 to 5 (median: 2) The most recognized alarm signs and symptoms were: bloody stools in 90.4% (n = 113), hypertonia of the extremities 89.6% (n = 112), persistent crying 81.6% (n = 102), loss of appetite after 5 hours of feeding 75.2% (n = 94). Regarding lack of knowledge, 72.8% (n = 91) did not know the temperature value considered as fever and 56% (n = 70) did not recognize drowsiness as an immediate alarm sign. 48% of the puerperal women recognized between 7 to 8 signs and symptoms of alarms Conclusion. The puerperal women surveyed had an adequate level of recognition of alarm signs.

Conocimientos de puérperas del servicio de alojamiento conjunto de un hospital de alta complejidad sobre los cuidados del recién nacido en el hogar / Knowledge of puerperal in a rooming-in of a hospital of high complexity about the care of the newborn in the home

Introducción: Los cuidados del recién nacido en el hogar son fundamentales para lograr un adecuado crecimiento y desarrollo y prevenir la morbimortalidad de los mismos. Objetivo: Describir el nivel de conocimiento sobre los cuidados del recién nacido en el hogar en puérperas del servicio de alojamiento conjunto de un hospital de referencia. Metodología: Estudio observacional, descriptivo, prospectivo, transversal en puérperas de la sala de alojamiento conjunto del Hospital Central del Instituto de Previsión Social de septiembre-octubre del 2021. Para la recolección de datos se utilizó encuestas con preguntas cerradas. Se analizaron la edad, escolaridad, paridad, conocimiento sobre la alimentación e higiene del recién nacido, cuidados del cordón umbilical, sueño, vestimenta y termorregulación. El análisis de datos se realizó en Spss v.23, utilizando estadística descriptiva. Se solicitó consentimiento informado verbal. Resultados: Participaron 125 puérperas entre 19 a 42 años (edad media: 28,9 ± 6,03), paridad mediana de 2, con escolaridad universitaria 41,6 % (52/125), se encontró que el 32,2 % (40/125) de las puérperas tenían un alto nivel de conocimiento sobre los cuidados del recién nacido en el hogar, el 48,8% (61/125) tenían un nivel medio de conocimiento, mientras que el 19% (24/125) presentaba un bajo nivel de conocimiento. Conclusión: Un elevado porcentaje de puérperas del servicio de alojamiento conjunto tienen un óptimo conocimiento sobre los cuidados del recién nacido en el hogar.

Introduction: Newborn care at home is essential to achieve adequate growth and development and prevent morbidity and mortality. Objective: To describe the level of knowledge about newborn care at home in puerperal women in at rooming-in of a referral hospital. Methodology: Observational, descriptive, prospective, crosssectional study in puerperal women in at rooming-in of the Central Hospital of the Social Security Institute from September-October 2021. Surveys with closed questions were used for data collection. Age, schooling, parity, knowledge of newborn feeding and hygiene, umbilical cord care, sleep, clothing and thermoregulation were analyzed. The data analysis was carried out in Spss v.23, using descriptive statistics. Verbal informed consent was requested. Results: 125 puerperal women between 19 to 42 years old participated (mean age: 28.9 ± 6.03), median parity of 2, with university education 41.6% (52/125), it was found that 32.2% (40/125) of the puerperal women had a high level of knowledge about newborn care at home, 48.8% (61/125) had a medium level of knowledge, while 19% (24/125) had a low level of knowledge. Conclusion: A high percentage of puerperal women in at rooming-in have an optimal knowledge about the care of the newborn at home.

Infecciones asociadas a catéter venoso central en pacientes internados en el servicio de pediatría del Hospital Central del Instituto de Previsión Social de abril del 2020 a abril de 2021 / Central venous catheter-associated infections in patients admitted to the pediatric service of the Central Hospital of the Social Security Institute from April 2020 to April 2021

Introducción: Los catéteres venosos centrales (CVC) son de gran utilidad para el diagnóstico y tratamiento en varias enfermedades; las infecciones asociadas al mismo es una de las complicaciones más frecuentes. Objetivo: Describir las características de las infecciones asociadas al uso de catéter venoso central en el servicio de pediatría del Hospital Central del Instituto de Previsión Social de abril del 2020 a abril de 2021. Metodología: Estudio observacional, descriptivo, retrospectivo de corte transversal de pacientes del servicio de pediatría del Hospital Central de IPS que requirieron la colocación de catéter venoso central entre abril de 2020 a abril del 2021. Las variables analizadas fueron la edad, sexo, comorbilidades, sitio de inserción, intervalo de tiempo hasta la infección y gérmenes aislados. Los datos se analizaron en SPSS v.23, utilizando estadística descriptiva. Resultados: Se incluyeron 198 pacientes con CVC (edad media: 64,3 ± 58,8 meses), 53% de sexo masculino (n=105), 41,4% con patologías quirúrgicas (n=82), 26,8% hematoncológicas (n=53), infecciosas 21,7% (n=43). La frecuencia de infecciones asociadas fue del 16,2 % (n=32), el tiempo para las infecciones fue 11,5 ± 3,3 días, los gérmenes asociados fueron el Staphylococcus coagulasa negativo (n=9) y Klebsiella pneumoniae (n=6). El 12 % (4/32) de los pacientes presentó bacteremia concomitante con aislamiento en hemocultivos del mismo gérmen encontrado en el CVC, los cuales fueron en mayor frecuencia Staphylococcus aureus. Conclusión: Las infecciones asociadas a CVC se presentaron en alrededor de la cuarta parte de los pacientes. El germen responsable con más frecuencia fue el S. coagulasa negativo.

Introduction: Central venous catheters (CVC) are very useful for the diagnosis and use of treatment in various diseases, infections associated with it are one of the most frequent complications. Objective: To describe the characteristics of the infections associated with the use of a CVC in the pediatric service of the Central Hospital of the Social Security Institute from April 2020 to April 2021. Methodology: Observational, descriptive, retrospective cross-sectional study in patients from the pediatric service of the IPS Central Hospital who required the placement of a central venous catheter during the period from April 2020 to April 2021. The variables analyzed were age, sex, comorbidities, insertion site, interval of time, isolated germs. SPSS v.23 was used for data analysis, using descriptive statistics. Results: 198 patients with CVC were included with a mean age of 64.3 ± 58.8 months, 53% male (n = 105), 41.4% with surgical pathologies (n = 82), 26. 8% hematological (n = 53), infectious 21.7% (n = 43). The frequency of associated associates was 16.2% (n = 32), the mean time for infections was 11.5 ± 3.3 days, the germs most frequently associated were negative-coagulase Staphylococcus (n = 9) and Klebsiella pneumoniae (n = 6). 12% (4/32) of the patients presented concomitant bacteremia with isolation in blood cultures of the same germs that were found in the central venous catheter, which were Staphylococcus aureus more frequently. Conclusion: The frequency of infections associated with CVC occurs in around a quarter of the population studied. The most frequently responsible germ was negative-coagulase Staphylococcus.

Duration of the Presence of Infectious Zika Virus in Semen and Serum.

Zika virus (ZIKV) has recently caused a large epidemic in the Americas that is associated with birth defects. Although ZIKV is primarily transmitted by Aedes mosquitoes, ZIKV RNA is detectable in blood and semen of infected individuals for weeks or months, during which sexual and other modes of transmission are possible. However, viral RNA is usually detectable longer than infectious virus is present. We determined the frequency of isolation of infectious virus from semen and serum samples prospectively obtained from a cohort of patients in Puerto Rico. We confirmed isolation of infectious virus on the basis of a tissue culture cytopathic effect, an increase in virus genome copy equivalents (GCE), and positive results of immunofluorescence analysis; virus in infected cells was quantitated by flow cytometry. These criteria confirmed the presence of infectious virus in semen specimens from 8 of 97 patients for up to 38 days after initial detection when virus loads are >1.4 × 106 genome copy equivalents/mL. Two serum isolates were obtained from 296 patients. These findings can help guide important prevention guidelines for persons that may potentially be infectious and transmit ZIKV sexually.

Novel junctophilin-2 mutation A405S is associated with basal septal hypertrophy and diastolic dysfunction.

BACKGROUND: Hypertrophic cardiomyopathy (HCM), defined as asymmetric left ventricular hypertrophy, is a leading cause of cardiac death in the young. Perturbations in calcium (Ca2+) handling proteins have been implicated in the pathogenesis of HCM. JPH2-encoded junctophilin 2 is a major component of the junctional membrane complex, the subcellular microdomain involved in excitation-contraction coupling. We hypothesized that a novel JPH2 mutation identified in patients with HCM is causally linked to HCM, and alters intracellular Ca2+ signaling in a pro-hypertrophic manner. OBJECTIVES: To determine using a transgenic mouse model whether a JPH2 mutation found in a HCM patient is responsible for disease development. METHODS: Genetic interrogation of a large cohort of HCM cases was conducted for all coding exons of JPH2. Pseudo-knock-in (PKI) mice containing a novel JPH2 variant were subjected to echocardiography, cardiac MRI, hemodynamic analysis, and histology. RESULTS: A novel JPH2 mutation, A405S, was identified in a genotype-negative proband with significant basal septal hypertrophy. Although initially underappreciated by traditional echocardiographic imaging, PKI mice with this JPH2 mutation (residue A399S in mice) were found to exhibit similar basal hypertrophy using a newly developed echo imaging plane, and this was confirmed using cardiac MRI. Histological analysis demonstrated cardiomyocyte hypertrophy and disarray consistent with HCM. CONCLUSIONS: Variant A405S is a novel HCM-associated mutation in JPH2 found in a proband negative for mutations in the canonical HCM-associated genes. Studies in the analogous mouse model demonstrated for the first time a causal link between a JPH2 defect and HCM. Moreover, novel imaging approaches identified subvalvular septal hypertrophy, specific findings also reported in the human JPH2 mutation carrier.

SPEG (Striated Muscle Preferentially Expressed Protein Kinase) Is Essential for Cardiac Function by Regulating Junctional Membrane Complex Activity.

RATIONALE: Junctional membrane complexes (JMCs) in myocytes are critical microdomains, in which excitation-contraction coupling occurs. Structural and functional disruption of JMCs underlies contractile dysfunction in failing hearts. However, the role of newly identified JMC protein SPEG (striated muscle preferentially expressed protein kinase) remains unclear. OBJECTIVE: To determine the role of SPEG in healthy and failing adult hearts. METHODS AND RESULTS: Proteomic analysis of immunoprecipitated JMC proteins ryanodine receptor type 2 and junctophilin-2 (JPH2) followed by mass spectrometry identified the serine-threonine kinase SPEG as the only novel binding partner for both proteins. Real-time polymerase chain reaction revealed the downregulation of SPEG mRNA levels in failing human hearts. A novel cardiac myocyte-specific Speg conditional knockout (MCM-Spegfl/fl) model revealed that adult-onset SPEG deficiency results in heart failure (HF). Calcium (Ca2+) and transverse-tubule imaging of ventricular myocytes from MCM-Spegfl/fl mice post HF revealed both increased sarcoplasmic reticulum Ca2+ spark frequency and disrupted JMC integrity. Additional studies revealed that transverse-tubule disruption precedes the development of HF development in MCM-Spegfl/fl mice. Although total JPH2 levels were unaltered, JPH2 phosphorylation levels were found to be reduced in MCM-Spegfl/fl mice, suggesting that loss of SPEG phosphorylation of JPH2 led to transverse-tubule disruption, a precursor of HF development in SPEG-deficient mice. CONCLUSIONS: The novel JMC protein SPEG is downregulated in human failing hearts. Acute loss of SPEG in mouse hearts causes JPH2 dephosphorylation and transverse-tubule loss associated with downstream Ca2+ mishandling leading to HF. Our study suggests that SPEG could be a novel target for the treatment of HF.

Junctophilin-2 gene therapy rescues heart failure by normalizing RyR2-mediated Ca2+ release.

BACKGROUND: Junctophilin-2 (JPH2) is the primary structural protein for the coupling of transverse (T)-tubule associated cardiac L-type Ca channels and type-2 ryanodine receptors on the sarcoplasmic reticulum within junctional membrane complexes (JMCs) in cardiomyocytes. Effective signaling between these channels ensures adequate Ca-induced Ca release required for normal cardiac contractility. Disruption of JMC subcellular domains, a common feature of failing hearts, has been attributed to JPH2 downregulation. Here, we tested the hypothesis that adeno-associated virus type 9 (AAV9) mediated overexpression of JPH2 could halt the development of heart failure in a mouse model of transverse aortic constriction (TAC). METHODS AND RESULTS: Following TAC, a progressive decrease in ejection fraction was paralleled by a progressive decrease of cardiac JPH2 levels. AAV9-mediated expression of JPH2 rescued cardiac contractility in mice subjected to TAC. AAV9-JPH2 also preserved T-tubule structure. Moreover, the Ca2+ spark frequency was reduced and the Ca2+ transient amplitude was increased in AAV9-JPH2 mice following TAC, consistent with JPH2-mediated normalization of SR Ca2+ handling. CONCLUSIONS: This study demonstrates that AAV9-mediated JPH2 gene therapy maintained cardiac function in mice with early stage heart failure. Moreover, restoration of JPH2 levels prevented loss of T-tubules and suppressed abnormal SR Ca2+ leak associated with contractile failure following TAC. These findings suggest that targeting JPH2 might be an attractive therapeutic approach for treating pathological cardiac remodeling during heart failure.

Possible Role of Interaction between PPARα and Cyclophilin D in Cardioprotection of AMPK against In Vivo Ischemia-Reperfusion in Rats.

Activated AMPK protects the heart from cardiac ischemia-reperfusion (IR) injury and is associated with inhibition of mitochondrial permeability transition pore (PTP) opening. On the other hand, pharmacological inhibition of the PTP reduces infarct size and improves cardiac function. However, it is unclear whether beneficial effects of AMPK are mediated through the PTP and, if they are not, whether simultaneous activation of AMPK and inhibition of the PTP exert synergistic protective effects against cardiac IR injury. Here, we examined the effects of the AMPK activator, A-769662 in combination with the PTP inhibitor, sanglifehrin A (SfA) on in vivo cardiac IR. Cardiac dysfunction following IR injury was associated with decreased activity of the mitochondrial electron transport chain (ETC) and increased mitochondrial ROS and PTP opening. Administration of A-769662 or SfA individually upon reperfusion improved cardiac function, reduced infarction size, and inhibited ROS production and PTP opening. However, simultaneous administration of SfA and A-769662 did not provide synergistic improvement of postischemic recovery of cardiac and mitochondrial function, though both compounds disrupted IR-induced interaction between PPARα and CyP-D. In conclusion, A-769662 or SfA prevents PPARα interaction with CyP-D, improving cardiac outcomes and increasing mitochondrial function, and simultaneous administration of the drugs does not provide synergistic effects.

Obesidad y perfil lipídico en trabajadores del Centro Nacional de Genética Médica / Obesity and lipid profile in employees of the National Center of Medical Genetics

Introducción: El aumento en la prevalencia del sobrepeso y obesidad se ha convertido un importante problema de salud a nivel mundial. La obesidad general y visceral se asocia con mayor riesgo para diferentes enfermedades. Objetivo: Analizar la asociación independiente de índices de adiposidad central con parámetros de la bioquímica sanguínea en sujetos adultos. Método: Se efectuó un estudio antropométrico en una muestra de 52 adultos de ambos sexos, trabajadores de Centro Nacional de Genética Médica, entre 20 y 76 años. Se obtuvo el peso, la talla, circunferencia cintura, circunferencia cadera y de determinó el Índice de Masa Corporal, Índice Cintura/Cadera, Índice Cintura/Talla. A partir de 5ml de sangre venosa, se realizó la determinación de las concentraciones de colesterol total y triglicéridos. Resultados: Existe un alto número de trabajadores con elevada grasa corporal, obesidad abdominal y altos niveles de triglicéridos en sangre. Al evaluar el riesgo a partir de la clasificación de cada índice antropométrico estudiado, solamente el índice Cintura/Talla detectó diferencias en la concentración de triglicéridos en sangre, entre sujetos con y sin obesidad abdominal. Conclusiones: Se pone de manifiesto la relación entre el sobrepeso/ obesidad y en especial de la obesidad abdominal, evaluada por el Índice Cintura Talla, con alteraciones metabólicas, específicamente con niveles elevados de triglicéridos en sangre…(AU)

Resultados del Programa de Prevención de Anemia Falciforme en el Centro Nacional de Genética Médica de Cuba (2008-2014) / Results of program for the prevention of sickle cell anemia in the National Center of Medical Genetics of Cuba (2008-2014)

La hemoglobina (Hb) es una proteína globular, se encuentra presente en altas concentraciones en los glóbulos rojos y transporta oxígeno a los tejidos. Las variantes de Hb son formas mutadas de la Hb, con una sustitución puntual de un aminoácido por otro. Las variantes estructurales más frecuentes en Cuba son HbS, HbC, HbD, HbE; y los tipos más frecuentes de anemia falciforme son SS y SC. El programa cubano de pesquisa de anemia por hematíes falciformes (AHF) comenzó en 1982, permitiendo la identificación precoz de portadores y la posibilidad de diagnóstico prenatal. El objetivo de este trabajo es describir los resultados obtenidos en el programa de AHF utilizando la tecnología Hydrasys. En el período 2008 2014 se realizó la pesquisa en las embarazadas de Artemisa, La Habana e Isla de la Juventud. Se analizaron muestras de sangre total con el gel de agarosa en medio alcalino y en medio ácido por la tecnología HYDRASYS. En estos años se han pesquisado 25137 gestantes, y se detectó el rasgo falciforme en 889. Los resultados de la pesquisa manifiesta la importancia de continuar y optimizar este programa en Cuba para brindar una mejor calidad y esperanza de vida…(AU)

Resultados del Programa de deficiencia de Biotinidasa en el Centro Nacional de Genética Médica: 2006-2014 / Results of Biotinidase deficiency Program in National Center of Medical Genetic: 2006-2014

El programa de pesquisa neonatal de deficiencia de biotinidasa se inició en Cuba en el 2005. Un año después se comienza a realizar la confirmación bioquímica en el Centro Nacional de Genética Médica. En el departamento de Genética Bioquímica de esta institución fueron estudiados 1016 neonatos con resultado de pesquisa positivo para la enfermedad, durante el período 2006-2014. Se confirmaron bioquímicamente 10 casos positivos, con igual distribución por sexo. De ellos, el 80 (percent) presentó deficiencia parcial, en tanto el 20(percent) restante se correspondió con la deficiencia profunda. Los pacientes estuvieron distribuidos entre las provincias de Artemisa, La Habana, Matanzas, Cienfuegos, Villa Clara, Holguín, Santiago de Cuba y Guantánamo. La incidencia estimada para esta enfermedad en Cuba fue de 1/110 032 nacidos vivos…(AU)

The beneficial effects of AMP kinase activation against oxidative stress are associated with prevention of PPARα-cyclophilin D interaction in cardiomyocytes.

AMP kinase (AMPK) plays an important role in the regulation of energy metabolism in cardiac cells. Furthermore, activation of AMPK protects the heart from myocardial infarction and heart failure. The present study examines whether or not AMPK affects the peroxisome proliferator-activated receptor-α (PPARα)/mitochondria pathway in response to acute oxidative stress in cultured cardiomyocytes. Cultured H9c2 rat embryonic cardioblasts were exposed to H2O2-induced acute oxidative stress in the presence or absence of metformin, compound C (AMPK inhibitor), GW6471 (PPARα inhibitor), or A-769662 (AMPK activator). Results showed that AMPK activation by metformin reverted oxidative stress-induced inactivation of AMPK and prevented oxidative stress-induced cell death. In addition, metformin attenuated reactive oxygen species generation and depolarization of the inner mitochondrial membrane. The antioxidative effects of metformin were associated with the prevention of mitochondrial DNA damage in cardiomyocytes. Coimmunoprecipitation studies revealed that metformin abolished oxidative stress-induced physical interactions between PPARα and cyclophilin D (CypD), and the abolishment of these interactions was associated with inhibition of permeability transition pore formation. The beneficial effects of metformin were not due to acetylation or phosphorylation of PPARα in response to oxidative stress. In conclusion, this study demonstrates that the protective effects of metformin-induced AMPK activation against oxidative stress converge on mitochondria and are mediated, at least in part, through the dissociation of PPARα-CypD interactions, independent of phosphorylation and acetylation of PPARα and CypD.

Crosstalk between AMPK activation and angiotensin II-induced hypertrophy in cardiomyocytes: the role of mitochondria.

AMP-kinase (AMPK) activation reduces cardiac hypertrophy, although underlying molecular mechanisms remain unclear. In this study, we elucidated the anti-hypertrophic action of metformin, specifically, the role of the AMPK/eNOS/p53 pathway. H9c2 rat cardiomyocytes were treated with angiotensin II (AngII) for 24 hrs in the presence or absence of metformin (AMPK agonist), losartan [AngII type 1 receptor (AT1R) blocker], Nω-nitro-L-arginine methyl ester (L-NAME, pan-NOS inhibitor), splitomicin (SIRT1 inhibitor) or pifithrin-α (p53 inhibitor). Results showed that treatment with metformin significantly attenuated AngII-induced cell hypertrophy and death. Metformin attenuated AngII-induced activation (cleavage) of caspase 3, Bcl-2 down-regulation and p53 up-regulation. It also reduced AngII-induced AT1R up-regulation by 30% (P < 0.05) and enhanced AMPK phosphorylation by 99% (P < 0.01) and P-eNOS levels by 3.3-fold (P < 0.01). Likewise, losartan reduced AT1R up-regulation and enhanced AMPK phosphorylation by 54% (P < 0.05). The AMPK inhibitor, compound C, prevented AT1R down-regulation, indicating that metformin mediated its effects via AMPK activation. Beneficial effects of metformin and losartan converged on mitochondria that demonstrated high membrane potential (Δψm ) and low permeability transition pore opening. Thus, this study demonstrates that the anti-hypertrophic effects of metformin are associated with AMPK-induced AT1R down-regulation and prevention of mitochondrial dysfunction through the SIRT1/eNOS/p53 pathway.

The role of PPARα in metformin-induced attenuation of mitochondrial dysfunction in acute cardiac ischemia/reperfusion in rats.

Metformin, an anti-diabetic drug, exerts cardioprotection against ischemia-reperfusion (IR) through the activation of AMPK. However, the molecular mechanisms underlying these beneficial effects remain elusive. In this study, we examined the role of PPARα in mediating cardioprotective effects of metformin on mitochondria. Hearts of male Sprague-Dawley rats perfused by Langendorff were subjected to IR in the presence or absence of metformin and the PPARß inhibitor, GW6471. IR reduced cardiac function and compromised the structural integrity of cardiac cells evidenced by increased LDH release from the hearts. In addition, IR induced mitochondrial dysfunction as evidenced by reduced respiration and increased mitochondrial permeability transition pore (PTP) opening. However, metformin-treated hearts demonstrated improved post-ischemic recovery of cardiac function and reduced cell death that were associated with increased state 3 respiration at complexes I and II (by 27% and 32%, respectively, both p < 0.05) and decreased PTP opening (by 27%, p < 0.05) compared to untreated hearts. The protective effects of metformin on cardiac function and mitochondria were blocked by GW6471. Thus, our results demonstrate that inhibition of PPARα attenuates the beneficial effects of metformin on mitochondria in acute IR.

Direct renin inhibition exerts an anti-hypertrophic effect associated with improved mitochondrial function in post-infarction heart failure in diabetic rats.

BACKGROUND: In addition to hypertension control, direct renin inhibition has been shown to exert direct beneficial effects on the heart in post-infarction cardiac remodeling. This study elucidates the possible contribution of mitochondria to the anti-hypertrophic effects of the direct renin inhibitor aliskiren in post-infarction heart failure complicated with diabetes in rats. METHODS: Diabetes was induced in male Sprague-Dawley rats by a single injection of streptozotocin (IP, 65 mg/kg body weight). After 7 days, the animals were randomly assigned to 4 groups: sham, heart failure, sham+aliskiren, and heart failure+aliskiren. Post-infarction HF was induced by coronary artery ligation for 4 weeks. RESULTS: showed that heart failure reduced ejection fraction and cardiac output by 41% (P<0.01) and 42% (P<0.05), respectively, compared to sham-operated hearts. Cardiac dysfunction was associated with suppressed state 3 respiration rates and respiratory control index in mitochondria, and increased mitochondrial permeability transition pore (PTP) opening. In addition, heart failure reduced expression of the major mitochondrial sirtuin, SIRT3 and increased acetylation of cyclophilin D, a regulatory component of the PTP. Aliskiren significantly improved cardiac function and abrogated mitochondrial perturbations. CONCLUSION: Our results demonstrate that aliskiren attenuates post-infarction remodeling which is associated with its beneficial effects on mitochondria.

Targeting the mitochondrial permeability transition: cardiac ischemia-reperfusion versus carcinogenesis.

Cardiovascular diseases and cancer continue to be major causes of death worldwide, and despite intensive research only modest progress has been reached in reducing the morbidity and mortality of these awful diseases. Mitochondria are broadly accepted as the key organelles that play a crucial role in cell life and death. They provide cells with ATP produced via oxidative phosphorylation under physiological conditions, and initiate cell death through both apoptosis and necrosis in response to severe stress. Oxidative stress accompanied by calcium overload and ATP depletion induces the mitochondrial permeability transition (mPT) with formation of pathological, non-specific mPT pores (mPTP) in the mitochondrial inner membrane. Opening of the mPTP with a high conductance results in matrix swelling ultimately inducing rupture of the mitochondrial outer membrane and releasing pro-apoptotic proteins into the cytoplasm. The ATP level is the determining factor in deciding whether cells die through apoptosis or necrosis. Cardiac cells undergoing ischemia followed by reperfusion (IR) possess exactly the same conditions mentioned above to induce mPTP opening. Due to its critical role in cell death, inhibition of mPTP opening has been accepted as a major therapeutic approach to protect the heart against IR. In contrast to cardiac IR, cancer cells exhibit less sensitivity to pore opening which can be in part explained by increased expression of mPTP compounds/modulators and metabolic remodeling. Since the main goal of chemotherapy is to provoke apoptosis, mPT induction may represent an attractive approach for the development of new cancer therapeutics to induce mitochondria-mediated cell death and prevent cell differentiation in carcinogenesis. This review focuses on the role of the mPTP in cardiac IR and cancer, and pharmacological agents to prevent or initiate mPT-mediated cell death, respectively in these diseases.