Levels of Small Extracellular Vesicles Containing hERG-1 and Hsp47 as Potential Biomarkers for Cardiovascular Diseases.

The diagnosis of cardiovascular disease (CVD) is still limited. Therefore, this study demonstrates the presence of human ether-a-go-go-related gene 1 (hERG1) and heat shock protein 47 (Hsp47) on the surface of small extracellular vesicles (sEVs) in human peripheral blood and their association with CVD. In this research, 20 individuals with heart failure and 26 participants subjected to cardiac stress tests were enrolled. The associations between hERG1 and/or Hsp47 in sEVs and CVD were established using Western blot, flow cytometry, electron microscopy, ELISA, and nanoparticle tracking analysis. The results show that hERG1 and Hsp47 were present in sEV membranes, extravesicularly exposing the sequences 430AFLLKETEEGPPATE445 for hERG1 and 169ALQSINEWAAQTT- DGKLPEVTKDVERTD196 for Hsp47. In addition, upon exposure to hypoxia, rat primary cardiomyocytes released sEVs into the media, and human cardiomyocytes in culture also released sEVs containing hERG1 (EV-hERG1) and/or Hsp47 (EV-Hsp47). Moreover, the levels of sEVs increased in the blood when cardiac ischemia was induced during the stress test, as well as the concentrations of EV-hERG1 and EV-Hsp47. Additionally, the plasma levels of EV-hERG1 and EV-Hsp47 decreased in patients with decompensated heart failure (DHF). Our data provide the first evidence that hERG1 and Hsp47 are present in the membranes of sEVs derived from the human cardiomyocyte cell line, and also in those isolated from human peripheral blood. Total sEVs, EV-hERG1, and EV-Hsp47 may be explored as biomarkers for heart diseases such as heart failure and cardiac ischemia.

Tratamiento endovascular de aneurisma disecante de la arteria basilar con dispositivo redireccionador de flujo FRED: primer reporte de caso en Colombia / Basilar dissecting aneurysm successfully treated by FRED Flow-Diverter device: first case report in Colombia

RESUMEN INTRODUCCIÓN: Los aneurismas disecantes de la arteria basilar tienen un curso clínico impredecible que, eventualmente, evoluciona a un accidente cerebrovascular hemorrágico o isquémico grave. Por otro lado, su abordaje terapéutico es controvertido y no existen líneas claras de tratamiento. CASO CLÍNICO: Presentamos el caso de una mujer de 28 años con un infarto del tallo cerebral secundario a aneurisma disecante de la arteria basilar, tratado exitosamente con dispositivo endoluminal redireccionador de flujo (FRED). CONCLUSIÓN: El tratamiento endovascular con FRED de los aneurismas disecantes parece ofrecer ventajas sobre las técnicas quirúrgicas abiertas y stents tradicionales, en casos seleccionados.

SUMMARY INTRODUCTION. Dissecting basilar artery aneurysms have an unpredictable course, eventually evolving to serious hemorrhagic or ischemic stroke; on the other hand, its therapeutic approach in controversial and there are no clear lines of treatment. CASE REPORT. We report a case of a 28-year-old female with brain stem infarction secondary to basilar dissecting aneurysm successfully treated by Flow-Redirection Endoluminal Device (FRED). CONCLUSION. Endovascular treatment of dissecting basilar artery aneurysms with FRED seems to offer advantages over traditional open surgical techniques and conventional stents in selected cases.

Características epidemiológica de la enfermedad de Chikungunya en Guazacapán, Santa Rosa en el período de marzo a diciembre 2015

Introducción. Esta enfermedad viral aguda transmitida por mosquitos Aedes y Albopictus que se puede manifestar desde formas de molestias leves hasta severas con fiebres altas y síntomas severos que afectan el sistema musculo esquelético con duración a veces por tiempos prolongados después del ataque agudo de la virosis. Objetivos. Describir las manifestaciones clínicas agudas y características epidemiológicas de pacientes sospechosos de Chikungunya, de acuerdo al Protocolo de Vigilancia Epidemiológica del Centro Nacional de Epidemiología (PVE), que fueron atendidos en el Centro de Salud del Distrito de Guazacapán (CSG), durante marzo a diciembre del 2015. Metodología. Estudio retrospectivo descriptivo. Se utilizó SIGSA 3 (sistema gerencial de salud) del CSG y Santa Rosa, Historias Clínicas de los pacientes y fichas del PVE. Estudio descriptivo con uso de proporciones y tabla de contingencia de 2x2 para obtención de sensibilidad y especificidad. Resultados. Se diagnosticaron 40% casos de Dengue y 60% de Chikungunya. Por Nexo epidemiológico (caso que cumple con los criterios de la definición clínica de caso y que está epidemiológicamente ligado en forma directa a un caso confirmado por laboratorio) 88% y 12% por pruebas confirmatorias para Chikungunya. Conclusión. La definición de caso establecida por el PVE tiene baja sensibilidad y una especificidad adecuada para el diagnóstico de la enfermedad de Chikungunya. La mayoría de diagnósticos de Chikungunya se hacen por Nexo Epidemiológico, los únicos con prueba confirmatoria son con fines de vigilancia epidemiológica. La fiebre está presente en todos los pacientes con Chikungunya. La Enfermedad de Chikungunya es más frecuente en mujeres dentro de la tercera década de la vida y está presente durante todo el año, en varios sectores y varía poco entre las semanas epidemiológicas. Palabras clave: Chikungunya, Ficha epidemiológica, Definición de caso, Diagnóstico, Nexo epidemiológico

Introduction: This acute viral disease transmitted by Aedes and Albopictus mosquitoes can manifest from forms of mild to severe discomfort with high fevers and severe symptoms that affect the skeletal muscle system with a prolonged duration of time after the acute attack. Objective: To describe the acute clinical and epidemiological characteristics of patients suspected of Chikungunya, according to the Protocol of Epidemiological Surveillance of the National Epidemiology Center. Subjects treated at the Health Center District of Guazacapán from March to December 2015. Methodology: Retrospective, descriptive. It was used the SIGSA 3 of CSG and Santa Rosa, Medical Records and Epidemiological Surveillance Protocol. Descriptive study using proportions and 2x2 contingency table for obtaining sensitivity and specificity. Results: 40% Dengue and 60%Chikungunya. 88% was diagnosed epidemiologically linked and 12% for confirmatory tests for Chikungunya. Sensitivity and specificity of clinical conditions as Surveillance Protocol for diagnosis of Chikungunya: 55.33% and 92% respectively. Common symptoms: fever 100%, cutaneous manifestations 83%, arthralgia 74%, myalgia 67% and back pain 59%. Most frequent age range: 30-39 years. Gender 1.1: 1 F: M. Frequently epidemiological weeks 13 and 18. Residencies predisposition: La Poza de agua, El Astillero, San Pedro y Platanares. Conclusion: The case definition established by the Epidemiological Surveillance Protocol of the National Epidemiological Center of Guatemala has low sensitivity and adequate specificity for diagnosis of Chikungunya disease. Most Chikungunya diagnoses are made by epidemiological nexus, the confirmatory tests are done only to know the surveillance. Fever is present in all patients with Chikungunya. Chikungunya disease is more common in women in the third decade of life and is present throughout the year, in various sectors and varies by small amount between epidemiological weeks. Key Words: Chikungunya, Epidemiological record, Case definition, Diagnosis

Oxidative damage and nitric oxide synthase induction by surgical uteroplacental circulation restriction in the rabbit fetal heart.

OBJECTIVE: This study investigated the role of oxidative damage and nitric oxide (NO) synthases in the fetal heart using a model of intrauterine growth restriction induced by uteroplacental circulation restriction (UCR). METHODS: New Zealand white rabbits kept under 12-h light cycles, with food and water provided ad libitum, were subjected at day 25 of pregnancy to 40-50% uteroplacental artery ligation. We analyzed the gene expression of enzymes linked to nitric oxide synthesis (iNOS, eNOS, HO-1, and ARG-2), hypoxia inducible factor 1 alpha (HIF-1α), and the state of oxidative stress (protein carbonyl levels) in fetal heart homogenates. Additionally, we studied the histological morphology of the fetal heart. RESULTS: We found that fetal growth restriction was associated with a significant reduction in heart weight but a normal heart/body weight ratio in UCR animals. Hematoxylin and eosin staining showed normal left and right ventricular thickness but increased vessel dilatation with hyperemia in the hearts of the UCR group. We observed HIF-1α, eNOS, p-eNOS, and iNOS induction concomitant with intensified protein carbonyl levels but observed no changes in HO-1 or ARG-2 expression, suggesting increased NO and oxidative stress in the hearts of UCR animals. CONCLUSION: Uteroplacental circulation restriction increased NO-linked enzymes, oxidative damage, and dilated coronary vessels in fetal hearts. © 2017 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd.

En el Infarto agudo al miocardio los niveles plasmáticos de microvesículas extracelulares se elevan más precozmente que el aumento de la Troponina-I / Plasma levels of extracellular macrovesicles are elevated earlier than troponin-I in patients with myocardial infarction

Introducción: La Troponina I (TnI) plasmática es el biomarcador "Gold" estándar utilizado en diagnóstico de Infarto Agudo al Miocardio (IAM), indicando necrosis cardíaca. Las microvesículas extracelulares (MVEC), participan en comunicación celular, por lo que estudiar su distribución entregaría información respecto del evento isquémico, antesala del infarto. Objetivo: Estudiar las MVECs plasmáticas en pacientes con Síndrome Coronario Agudo (SCA) y compararlas con los niveles de TnI. Métodos: Plasma de 22 pacientes controles se recolectó 0-2hrs post-ingreso a urgencia. Plasma de 45 pacientes SCA se recolectó 0-2, 6-8 y 10-14hrs post ingreso, junto con la toma de muestra para estudio de TnI. Las MVECs plasmáticas fueron enriquecidas mediante kit comercial. La determinación de la concentración y tamaño MVECs se realizó por NTA (Nanoparticles Tracking Assay) usando el equipo Nanosight. Resultados: La concentración promedio de MVECs 0-2 hrs post ingreso fue 7,2 veces superior en plasma de pacientes con SCA vs controles y la moda del tamaño disminuyó en pacientes con SCA. La TnI no mostró diferencias significativas en 0-2 hrs post ingreso en el grupo estudiado. La concentración de las MVEC disminuyó significativamente después de 10-14 hrs post ingreso, mientras que la concentración promedio TnI se mantuvo invariable demostrando el aumento de MVECs previo al incremento de TnI. Conclusión. El aumento de MVECs previo al incremento de la TnI en pacientes infartados, sugiere que las MVECs aumentan en la fase previa del IAM, como respuesta al daño tisular. Actualmente, estudiamos el contenido molecular de las MVECs, para establecer un método diagnóstico del Síndrome Coronario Agudo basado en MVECs.

Background: Troponin I (TnI) is the gold standard used to establish the diagnosis of myocardial infarction (AMI), indicating the presence of myocardial necrosis. Extracellular micro vesicles are involved in cellular communication. Their distribution may provide information relating to the development of AMI in patients with acute coronary syndromes (ACS) Aim: to study plasma levels of ECMV compared to those of TnI in patients with ACS. Methods: The plasma levels of TnI and ECMV from 22 control patients coming to the emergency units was compared to plasma from 45 patients with ACS. Levels of both parameters were determined 0-2, 6-8 and 10-14 hours post admission. ECMVs were enriched by means of a commercial kit. Concentration and size of ECMV was determined by NTA (Nanoparticles tracking assay) using the Nanosight equipment. Results: Plasma concentration of ECMV was 7.2 times higher than that of TnI 0-2 hrs post admission. The mode of ECMV size was lower in patients with ACS. Concentration of ECMV had decreased significantly 10-14 hrs post admission, whereas the TnI levees remained stable. Conclusion: The increase in ECMV earlier than TnI in AMI suggests that ECMV are elevated in the pre-AMI phase, as a response to early tissue damage. A study of cellular content of ECMV, being carried out, may lead to develop a method for the early diagnosis of AMI in patients with ACS.

Nitric oxide synthase and changes in oxidative stress levels in embryonic kidney observed in a rabbit model of intrauterine growth restriction.

OBJECTIVE: This work aimed to study the effect of uteroplacental circulation restriction on endothelial kidney damage in a fetal rabbit model. METHODS: New Zealand rabbits were subjected to 40% to 50% of uteroplacental artery ligation at day 25 of pregnancy. After 5 days, surviving fetuses were harvested by cesarean section. The gene and protein expressions of selected enzymes associated with nitric oxide production and oxidative stress were analyzed in fetal kidney homogenates. RESULTS: The placenta weight (6.06 ± 0.27, p < 0.0319) and fetal body (19.90 ± 1.03, p < 0.0001) were significantly reduced in the uteroplacental circulation restriction group. The kidneys from restricted fetuses presented a mild vascular congestion and glomerular capillary congestion, without inflammation or hypertrophy. We found endothelial nitric oxide synthase phosphorylation inhibition (0.23 ± 0.13, p < 0.012) and arginase-2 (0.29 ± 0.14, p < 0.023) protein induction in fetal kidneys of the circulation restriction group. Finally, the kidneys from circulation-restricted fetuses showed increased inducible nitric oxide synthase messenger RNA (mRNA) (2.68 ± 0.24, p < 0.01) and reduced heme oxygenase-1 mRNA (23 ± 1.3, p < 0.003), with increased reactive oxygen species (1.69 ± 0.09, p < 0.001) and nitrotyrosine protein (1.74 ± 0.28, p < 0.003) levels, without changes in Nox mRNA. CONCLUSION: We describe significant deregulation of vascular activity and oxidative damage in kidneys of fetal rabbits that have been exposed to restriction of the uterine circulation. © 2016 John Wiley & Sons, Ltd.

Trombosis de la arteria renal en un recién nacido: presentación de un caso y revisión / Thrombosis in renal artery in a newborn: presentation a review of a case

Se describe un neonato que presenta cifras tensionales elevadas y ausencia de pulsos en miembros inferiores en su cuarto día de vida después de la colocación de un catéter umbilical arterial, evidenciando trombosis en arteria aorta y renal izquierda. Se realizó gammagrafía con MAG 3 que mostró exclusión renal izquierda y angioresonancia de aorta y renal izquierda. Se inició manejo con heparina no fraccionada y estreptoquinasa durante 6 horas. Se recuperó totalmente el compromiso en miembros inferiores, mejorando cifras tensionales a los pocos días. Estudios de seguimiento de función renal y crecimiento evidencian flujo de arteria renal izquierda y algo de función. Se describe mejoría con tratamiento anticoagulante y trombolítico de un riñón neonatal a pesar de sufrir isquemia prolongada.

This report describes a newborn who presents high pressure values and absence of pulses in inferior extremities in his 4th day of life. Posterior to placement of umbilical arterial catheter, confirming diagnostic of thrombosis in aorta and left renal artery. A gamagraphy with MAG 3 was performed that gave evidence of left renal exclusion and aorta and left renal angioresonance. A management with no fractional heparin and streptokinase during 6 hours was initiated. The compromise in lower extremities was totally recovered, improving presure values in a few days. Following studies of renal function and growth give evidence of left renal artery flow and some function. This report describes an improvement with anticoagulant and thrombolitic treatment of a newborn kidney depite of a prolonged ischemia.

Epidemiología de Campo: FETP II Guatemala

Contiene: Investigación de campo (Brotes de Malaria, Enfermedad Diarreica, Intoxicación por Alimentos, Leptospirosis), Análisis de Vigilancia (Malaria, Virus respiratorio e Influenza, deshidratacion), Estudios Epidemiológicos (Vacunación, Infecciones respiratorias, lesiones, hipertensión arterial), Presentaciones en conferencias científicas internacionales.