TNF-α Plus IL-1ß Induces Opposite Regulation of Cx43 Hemichannels and Gap Junctions in Mesangial Cells through a RhoA/ROCK-Dependent Pathway.

Connexin 43 (Cx43) is expressed in kidney tissue where it forms hemichannels and gap junction channels. However, the possible functional relationship between these membrane channels and their role in damaged renal cells remains unknown. Here, analysis of ethidium uptake and thiobarbituric acid reactive species revealed that treatment with TNF-α plus IL-1ß increases Cx43 hemichannel activity and oxidative stress in MES-13 cells (a cell line derived from mesangial cells), and in primary mesangial cells. The latter was also accompanied by a reduction in gap junctional communication, whereas Western blotting assays showed a progressive increase in phosphorylated MYPT (a target of RhoA/ROCK) and Cx43 upon TNF-α/IL-1ß treatment. Additionally, inhibition of RhoA/ROCK strongly antagonized the TNF-α/IL-1ß-induced activation of Cx43 hemichannels and reduction in gap junctional coupling. We propose that activation of Cx43 hemichannels and inhibition of cell-cell coupling during pro-inflammatory conditions could contribute to oxidative stress and damage of mesangial cells via the RhoA/ROCK pathway.

Conocimiento de los médicos generales sobre complicaciones obstétricas asociadas a riesgo cardiovascular subsecuente / General practitioners’ knowledge about pregnancy complications associated with long-term cardiovascular risk

Resumen Introducción: La enfermedad cardiovascular (ECV) constituye la principal causa de mortalidad en mujeres; la preeclampsia (PE) y la diabetes mellitus gestacional (DMG) están asociadas a incremento en el riesgo de ECV. Objetivo: Evaluar el conocimiento de los médicos generales (MG) sobre complicaciones obstétricas asociadas a ECV. Métodos: Se envió a los MG un cuestionario electrónico anónimo basado en casos, diseñado para evaluar el entendimiento de la influencia de la historia obstétrica en el riesgo cardiovascular a largo plazo y el conocimiento general sobre riesgo de ECV. Resultados: La tasa de respuesta fue de 35 % (161/465). Los participantes reconocieron que la PE y la DMG son factores de riesgo para ECV (98 y 83 %, respectivamente) y reportaron las siguientes estrategias de tamizaje de ECV en mujeres con historial de PE y DMG: monitoreo de presión arterial (PE 100 %, DMG 46 %), cálculo de índice de masa corporal (PE 68 %, DMG 57 %), evaluación del perfil de lípidos (PE 71 %, DMG 57 %), hemoglobina glucosilada (PE 26 %, DMG 92 %) y glucosa en ayuno (PE 28 %, DMG 91 %). Conclusión: Las estrategias de tamizaje para identificar ECV en mujeres con antecedentes de PE y DMG reportadas por los MG fueron variables.

Abstract Introduction: Cardiovascular disease (CVD) is the leading cause of mortality in women; preeclampsia (PE) and gestational diabetes mellitus (GDM) are associated with an increased risk of CVD. Objective: To evaluate general practitioners (GP) knowledge about complicated pregnancies and their association with CVD. Methods: An anonymous case-based electronic questionnaire designed to assess the level of understanding on the influence of a history of pregnancy complications on long-term cardiovascular risk and general knowledge about CVD risk was sent to GPs. Results: The response rate was 35 % (161/465). The participants recognized that PE and GDM are risk factors for CVD (98 and 83 %, respectively), and reported the following CVD screening strategies in women with a history of PE and GDM: blood pressure monitoring (PE 100 %, GDM 46 %), body mass index calculation (PE 68 %, GDM 57 %), lipid profile evaluation (PE 71 %, GDM 57 %), glycated hemoglobin (PE 26 %, GDM 92 %), and fasting glucose (PE 28 %, GDM 91 %). Conclusion: GP-reported screening strategies to identify CVD in women with a history of PE and GDM were variable.

Pharmacological inhibition of the F1 -ATPase/P2Y1 pathway suppresses the effect of apolipoprotein A1 on endothelial nitric oxide synthesis and vasorelaxation.

AIM: The contribution of apolipoprotein A1 (APOA1), the major apolipoprotein of high-density lipoprotein (HDL), to endothelium-dependent vasodilatation is unclear, and there is little information regarding endothelial receptors involved in this effect. Ecto-F1 -ATPase is a receptor for APOA1, and its activity in endothelial cells is coupled to adenosine diphosphate (ADP)-sensitive P2Y receptors (P2Y ADP receptors). Ecto-F1 -ATPase is involved in APOA1-mediated cell proliferation and HDL transcytosis. Here, we investigated the effect of lipid-free APOA1 and the involvement of ecto-F1 -ATPase and P2Y ADP receptors on nitric oxide (NO) synthesis and the regulation of vascular tone. METHOD: Nitric oxide synthesis was assessed in human endothelial cells from umbilical veins (HUVECs) and isolated mouse aortas. Changes in vascular tone were evaluated by isometric force measurements in isolated human umbilical and placental veins and by assessing femoral artery blood flow in conscious mice. RESULTS: Physiological concentrations of lipid-free APOA1 enhanced endothelial NO synthesis, which was abolished by inhibitors of endothelial nitric oxide synthase (eNOS) and of the ecto-F1 -ATPase/P2Y1 axis. Accordingly, APOA1 inhibited vasoconstriction induced by thromboxane A2 receptor agonist and increased femoral artery blood flow in mice. These effects were blunted by inhibitors of eNOS, ecto-F1 -ATPase and P2Y1 receptor. CONCLUSIONS: Using a pharmacological approach, we thus found that APOA1 promotes endothelial NO production and thereby controls vascular tone in a process that requires activation of the ecto-F1 -ATPase/P2Y1 pathway by APOA1. Pharmacological targeting of this pathway with respect to vascular diseases should be explored.

Encefalopatía posterior reversible durante el puerperio, secundaria a eclampsia. Reporte de dos casos / Reversible posterior encephalopathy during puerperium secondary to eclampsia. Report of two cases

Resumen ANTECEDENTES: El síndrome de encefalopatía posterior reversible es una alteración rara, que aparece en el tercer trimestre del embarazo y en el puerperio, asociada con preeclampsia-eclampsia y síndrome de Hellp. Los estudios de radioimagen son decisivos para establecer el diagnóstico y diferenciarlo de otros trastornos neurológicos, por su tratamiento y pronóstico diferentes. CASOS CLÍNICOS: Reporte de dos casos de encefalopatía posterior reversible con factores de riesgo diferentes para su manifestación (choque séptico, insuficiencia orgánica múltiple y síndrome de preeclampsia-eclampsia). El diagnóstico se estableció con base en la enfermedad subyacente, la sospecha clínica y los hallazgos en la resonancia magnética. En ambos casos coincidió la mayor parte de los síntomas relacionados con eclampsia. El tratamiento oportuno y la corrección del desequilibrio hidroelectrolítico, ácido-base, sepsis y sobrecarga de volumen fueron decisivos para revertir el cuadro y prevenir la evolución del síndrome. El diagnóstico de encefalopatía posterior reversible se corroboró por estudios radiológicos. Las pacientes egresaron de cuidados intensivos con remisión completa del cuadro neurológico. CONCLUSIONES: La prevalencia de encefalopatía posterior reversible en pacientes embarazadas es desconocida, su manifestación obedece a diferentes causas y las mujeres suelen recuperarse completamente; sin embargo, el diagnóstico y tratamiento deben individualizarse en cada caso.

Abstract BACKGROUND: Reversible posterior encephalopathy syndrome is a rare entity. It occurs most frequently in the third trimester and puerperium, associated with cases of preeclampsia-eclampsia and Hellp's syndrome. Radioimage studies are basic for its diagnosis and must be differentiated from other neurological pathologies, due to its different treatment and prognosis. CASES REPORT: This study presents two cases of reversible posterior encephalopathy syndrome with different risk factors for its presentation (septic shock, multiple organ failure and preeclampsia-eclampsia syndrome). The diagnosis is based on the underlying disease, clinical suspicion and magnetic resonance findings. In both cases, most of the symptoms related to eclampsia. The timely treatment and correction of fluid-electrolyte imbalance, acid-base, sepsis and volume overload are decisive in reversing the condition and preventing the evolution of the syndrome. The diagnosis of reversible posterior encephalopathy was corroborated by radiological studies. The patients withdrew from the care unit with complete remission of the neurological symptoms. CONCLUSIONS: Reversible posterior encephalopathy is a rare entity, of unknown prevalence in the pregnant patient, which occurs for different reasons, with full recovery, but which requires a specific diagnosis and treatment.

Endothelium trans differentiated from Wharton's jelly mesenchymal cells promote tissue regeneration: potential role of soluble pro-angiogenic factors.

BACKGROUND: Mesenchymal stem cells have a high capacity for trans-differentiation toward many adult cell types, including endothelial cells. Feto-placental tissue, such as Wharton's jelly is a potential source of mesenchymal stem cells with low immunogenic capacity; make them an excellent source of progenitor cells with a potential use for tissue repair. We evaluated whether administration of endothelial cells derived from mesenchymal stem cells isolated from Wharton's jelly (hWMSCs) can accelerate tissue repair in vivo. METHODS: Mesenchymal stem cells were isolated from human Wharton's jelly by digestion with collagenase type I. Endothelial trans-differentiation was induced for 14 (hWMSC-End14d) and 30 (hWMSC-End30d) days. Cell phenotyping was performed using mesenchymal (CD90, CD73, CD105) and endothelial (Tie-2, KDR, eNOS, ICAM-1) markers. Endothelial trans-differentiation was demonstrated by the expression of endothelial markers and their ability to synthesize nitric oxide (NO). RESULTS: hWMSCs can be differentiated into adipocytes, osteocytes, chondrocytes and endothelial cells. Moreover, these cells show high expression of CD73, CD90 and CD105 but low expression of endothelial markers prior to differentiation. hWMSCs-End express high levels of endothelial markers at 14 and 30 days of culture, and also they can synthesize NO. Injection of hWMSC-End30d in a mouse model of skin injury significantly accelerated wound healing compared with animals injected with undifferentiated hWMSC or injected with vehicle alone. These effects were also observed in animals that received conditioned media from hWMSC-End30d cultures. CONCLUSION: These results demonstrate that mesenchymal stem cells isolated from Wharton's jelly can be cultured in vitro and trans-differentiated into endothelial cells. Differentiated hWMSC-End may promote neovascularization and tissue repair in vivo through the secretion of soluble pro-angiogenic factors.

Participación de las madres en el cuidado de los recién nacidos internados en un servicio de neonatología que aplica el modelo de maternidad centrada en la familia / Participation of mothers in the care of newborns admitted to a neonatal model applying family-centered maternity

La participación activa de las madres en las unidades de terapia intensiva neonatales es beneficiosa para sus recién nacidos, mejora su crecimiento, disminuye el riesgo de infecciones y se asocia con mayor producción de leche humana. El objetivo de este estudio fue cuantificar las actividades que desarrollan las madres dentro de la unidad y estimar la reducción del tiempo de enfermería atribuible a su presencia. Diseño: Transversal, descriptivo. Resultados: Durante una semana las madres realizaron 798 prácticas a las que se les podrían atribuir 75 horas y 23 minutos (percentilos 10-90: 16 -123 hs) de trabajo de enfermería. Conclusión: Este estudio permitió conocer y cuantificar las principales actividades asociadas al cuidado de las madres de los niños internados y se logró una reducción en la carga de trabajo de enfermería equivalente a más de 12 turnos de enfermería de 6 hs en una semana.

Active mothers participation in the neonatal intensive care units (NICU) is beneficial for their babies, improving body growth, reducing the risk of infections and is associated with increased production of human milk. The objective of this study was to quantify the activities that mothers do within the unit in the care of their babies and to estimate the reduction of nursing time attributable to their presence. Design: Descriptive, cross section. Results: During a week, mothers conducted 798 practices with an estimate of 75 hours and 23 minutes (Percentiles 10-90: 16 -123 hours) of nursing work. Conclusion: This study allowed us to know and quantify the main activities that mothers perform in the care of their own babies staying in the NICU, This activities represent a reduction in nursing workload equivalent to more than 12 nursing shifts of 6 hours in a week.