Objetivo: Determinar el valor predictivo del Índice Cerebro Placentario y del flujo anormal del Ductus Venoso de Aranzio, medido por velocimetría Doppler, en pacientes con preeclampsia, en relación a un resultado perinatal adverso. Materiales y métodos: Estudio prospectivo, no experimental, longitudinal, de tipo correlacional. Se realizaron exámenes ultrasonográficos Doppler para determinar el Índice Cerebro Placentario y el flujo anormal del Ductus Venoso de Aranzio, en los 7 días previos al parto, en 160 pacientes con diagnóstico de preeclampsia severa admitidas en la Unidad de Medicina Fetal y Diagnóstico Prenatal del Servicio de Obstetricia de Alto Riesgo del Hospital Guillermo Almenara Irigoyen – EsSalud. El resultado perinatal adverso fue definido por los siguientes parámetros: Cesárea por SFA, APGAR menor 7 a los 5´, Líquido amniótico meconial, Oligohidramnios, pH de la arteria umbilical menor 7,2, Admisión en UCI neonatal, RCIU. Se utilizó estadística descriptiva para la variable dependiente y estadística inferencial mediante el estadístico chi cuadrado (x²) y prueba exacta de Fisher, con un nivel de significancia de 0,05; confiabilidad del 95%. Además se calculó la sensibilidad, especificidad y valores predictivos positivo y negativo de la variable independiente. Conclusiones: Se ha demostrado que la alteración del Índice Cerebro Placentario y del Flujo del Ductus Venoso de Aranzio medido por flujometría Doppler fetal, detecta a más del 65% de los recién nacidos con resultado perinatal adverso e hipoxia fetal y se asocia a la ocurrencia del mismo. Además esta es una prueba predictiva, estadísticamente significativa, de RCIU y de oligohidramnios, en pacientes con preeclampsia severa. El presente estudio se realizó con un muestreo no aleatorio, por ende, este hecho de no aleatoriedad, pudiera plantear problemas de validez externa. / Objective: To ascertain the value of cerebral-placental ratio and the abnormal fluxo of Aranzio´s Ductus Venous and for identifying newborns with neonatal morbidity in pregnancies complicated by severe preeclampsia. Study Design: A longitudinal and correlational study of 160 patients with severe preeclampsia (PA > 160/110, proteinuria 3+) was performed Doppler study done by one operador within 7 days before delivery. An abnormal cerebral-placental ratio and abnormal resistance and pulsabilility index of ductus venous were used to identificate fetal asphixia (cardiac insuficiency). The results belong 5 percentile were considered abnormal. These results were matched with perinatal results considered as abnormal. Results: Maternal characteristic were: age 33, parity 1, primigravid 45%, prenatal care 85%, gestational age at enrollment 35,1 weeks. The probability of detection IUGR is 65% and oligohydramnios 61,2%. Conclusion: The cerebral-placental ratio and abnormal fluxo of Aranzio´s Ductus venous identifies 65 % or more of the newborns with severe neonatal morbidity in pregnancies with severe preeclampsia.

published_or_final_version / abstract / toc / Physiology / Master / Master of Philosophy

Insulin and cellular stressors both activate p38 MAPK. Insulin protects cardiac tissue in a p38 MAPK-dependent manner. Paradoxically, inhibiting p38 MAPK is also protective. Hsp27 phosphorylation is regulated by p38 MAPK. Insulin was tested in H9c2 cardiomyocytes subjected to media exchange, 6 hours of oxygen-glucose deprivation, and reoxygenation. Insulin suppressed stress-induced phosphorylation of Hsp27 due to media-exchange or oxygen-glucose deprivation. Surprisingly, insulin increased Hsp27 phosphorylation during reoxygenation. Insulin also reduced total p38 MAPK levels. Insulin before oxygen-glucose deprivation prevented both localization of Hsp27 to the nucleus and localization of phospho-p38 MAPK to the cytoplasm. Insulin during oxygen-glucose deprivation caused the localization of phospho-p38 MAPK in the cytoplasm, but did not increase Hsp27 phosphorylation until reoxygenation. In conclusion, insulin may protect before oxygen-glucose deprivation by redirecting phospho-p38 MAPK to the nucleus away from damaging pathways in the cytoplasm and protects during oxygen-glucose deprivation by priming phospho-p38 MAPK to phosphorylate Hsp27. / Insulin was used on a model on H9c2 myotubes to determine the effect of oxygen-glucose deprivation and reoxygenation on the localization and phosphorylation of Hsp27 and p38 MAPK

Spreading depression (SD) is an interesting and important phenomenon due to its role in mammalian pathologies such as migraine, seizures, and stroke. Until recently investigations of the mechanisms involved in SD have mostly utilized mammalian cortical tissue, however in my thesis I demonstrated that SD-like events occur in the CNS of an invertebrate model, Locusta migratoria. Locusts enter comas in response to stress during which neural and muscular systems shut down until the stress is removed, and this is believed to be an adaptive strategy to survive extreme environmental conditions. Using the ventilatory central pattern generator (vCPG) as a model circuit I was able to show that stress-induced arrest of vCPG function is associated with SD-like events in the locust metathoracic ganglion (MTG) that closely resemble cortical SD (CSD) in many respects, including mechanism of induction, extracellular potassium ion ([K+]o) changes, and propagation in areas equivalent to mammalian grey matter. SD-like events in the locust were characterized as abrupt [K+]o increases associated with electrical activity silence in the locust CNS that propagate to other areas within the MTG. In this thesis I described the generation of comas by several cellular stressors (hyperthermia, metabolic stressors, Na+/K+-ATPase inhibition, and KCl) and the associated SD-like events in the locust, provide a description of the similarities to CSD, and show how they can be manipulated both by stress preconditioning and pharmacologically. I showed that hyperthermic vCPG arrest can be preconditioned by prior heat shock (HS) treatment and induced-thermotolerance was associated with an increased rate of [K+]o clearance associated with vCPG recovery that was not linked to changes in ATP levels or total Na+/K+-ATPase activity. I also provided evidence for the involvement of the stress-sensor AMP-activated protein kinase (AMPK) in stress-induced comas in the locust. AMPK activation was linked to a switch in motor pattern behavior following recovery from anoxia-induced vCPG arrest and exacerbated repetitive SD-like events induced by ouabain (Na+/K+-ATPase inhibitor). I suggested that locust SD-like events are adaptive by conserving energy and preventing cellular damage, and I provided a model for the mechanism of SD onset and recovery in the locust nervous system. / Thesis (Ph.D, Biology) -- Queen's University, 2010-08-05 16:08:19.905

Transient Receptor Potential Melastatin 7 (TRPM7) is a ubiquitously expressed divalent cation channel implicated as a key regulator of neuronal cell death in stroke. Our research group has previously shown that TRPM7 dependent cytoskeletal regulation particularly via cofilin mediates neuronal death in oxygen glucose deprivation (in vitro stroke model). LIMK1 phosphorylation was also shown to decrease downstream of TRPM7 activation during anoxia. In the present study we investigated the effects of TRPM7 activation during anoxia, on three regulators of LIMK and cofilin; Rho-associated kinase 2 (ROCK2), P-21 activated kinase 3 (PAK3) and Slingshot family phosphatase 1 (SSH1). Our findings suggest that PAK3 activity is downregulated during OGD through TRPM7 independent mechanisms. However, SSH1 activity appears to be regulated downstream of TRPM7 in a manner that is consistent with LIMK and cofilin regulation. Overall, our work suggests that SSH1 is a new link between anoxia-induced TRPM7activity and cofilin hyperactivation.

Transient Receptor Potential Melastatin 7 (TRPM7) is a ubiquitously expressed divalent cation channel implicated as a key regulator of neuronal cell death in stroke. Our research group has previously shown that TRPM7 dependent cytoskeletal regulation particularly via cofilin mediates neuronal death in oxygen glucose deprivation (in vitro stroke model). LIMK1 phosphorylation was also shown to decrease downstream of TRPM7 activation during anoxia. In the present study we investigated the effects of TRPM7 activation during anoxia, on three regulators of LIMK and cofilin; Rho-associated kinase 2 (ROCK2), P-21 activated kinase 3 (PAK3) and Slingshot family phosphatase 1 (SSH1). Our findings suggest that PAK3 activity is downregulated during OGD through TRPM7 independent mechanisms. However, SSH1 activity appears to be regulated downstream of TRPM7 in a manner that is consistent with LIMK and cofilin regulation. Overall, our work suggests that SSH1 is a new link between anoxia-induced TRPM7activity and cofilin hyperactivation.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Univ., 2004. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Sydney, 2003. / Title from title screen (viewed 7 May 2008). Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the Dept. of Medicine, Faculty of Medicine. Includes bibliographical references. Also available in print form.