Disruption of the Mouse Blood-Brain Barrier by Small Extracellular Vesicles from Hypoxic Human Placentas.

Cerebrovascular complications, including cerebral edema and ischemic and hemorrhagic stroke, constitute the leading cause of maternal mortality associated with preeclampsia. The underlying mechanisms of these cerebrovascular complications remain unclear. However, they are linked to placental dysfunction and blood-brain barrier (BBB) disruption. Nevertheless, the connection between these two distant organs is still being determined. Increasing evidence suggests that the placenta releases signaling molecules, including extracellular vesicles, into maternal circulation. Extracellular vesicles are categorized according to their size, with small extracellular vesicles (sEVs smaller than 200 nm in diameter) considered critical signaling particles in both physiological and pathological conditions. In preeclampsia, there is an increased number of circulating sEVs in maternal circulation, the signaling function of which is not well understood. Placental sEVs released in preeclampsia or from normal pregnancy placentas exposed to hypoxia induce brain endothelial dysfunction and disruption of the BBB. In this protocol, we assess whether sEVs isolated from placental explants cultured under hypoxic conditions (modeling one aspect of preeclampsia) disrupt the BBB in vivo.

Efficacy of an Enterotoxigenic Escherichia coli (ETEC) Vaccine on the Incidence and Severity of Traveler's Diarrhea (TD): Evaluation of Alternative Endpoints and a TD Severity Score.

The efficacy of an Oral Whole Cell ETEC Vaccine (OEV) against Travelers' Diarrhea (TD) was reexamined using novel outcome and immunologic measures. More specifically, a recently developed disease severity score and alternative clinical endpoints were evaluated as part of an initial validation effort to access the efficacy of a vaccine intervention for the first time in travelers to an ETEC endemic area. A randomized, double-blind, placebo-controlled trial followed travelers to Guatemala or Mexico up to 28 days after arrival in the country following vaccination (two doses two weeks apart) with an ETEC vaccine. Fecal samples were collected upon arrival, departure, and during TD for pathogen identification. Serum was collected in a subset of subjects to determine IgA cholera toxin B subunit (CTB) antibody titers upon their arrival in the country. The ETEC vaccine's efficacy, utilizing a TD severity score and other alternative endpoints, including the relationship between antibody levels and TD risk, was assessed and compared to the per-protocol primary efficacy endpoint. A total of 1435 subjects completed 7-28 days of follow-up and had available data. Vaccine efficacy was higher against more severe (≥5 unformed stools/24 h) ETEC-attributable TD and when accounting for immunologic take (PE ≥ 50%; p < 0.05). The vaccine protected against less severe (3 and 4 unformed stools/24 h) ETEC-attributable TD when accounting for symptom severity or change in activity (PE = 76.3%, p = 0.01). Immunologic take of the vaccine was associated with a reduced risk of infection with ETEC and other enteric pathogens, and with lower TD severity. Clear efficacy was observed among vaccinees with a TD score of ≥4 or ≥5, regardless of immunologic take (PE = 72.0% and 79.0%, respectively, p ≤ 0.03). The vaccine reduced the incidence and severity of ETEC, and this warrants accelerated evaluation of the improved formulation (designated ETVAX), currently undergoing advanced field testing. Subjects with serum IgA titers to CTB had a lower risk of infection with ETEC and Campylobacter jejuni/coli. Furthermore, the TD severity score provided a more robust descriptor of disease severity and should be included as an endpoint in future studies.

Reduced Brain Cortex Angiogenesis in the Offspring of the Preeclampsia-Like Syndrome.

BACKGROUND: Children from pregnancies affected by preeclampsia have an increased risk of cognitive and behavioral alterations via unknown pathophysiology. We tested the hypothesis that preeclampsia generated reduced brain cortex angiogenesis in the offspring. METHODS: The preeclampsia-like syndrome (PELS) mouse model was generated by administering the nitric oxide inhibitor NG-nitroarginine methyl ester hydrochloride. Confirmatory experiments were done using 2 additional PELS models. While in vitro analysis used mice and human brain endothelial cells exposed to serum of postnatal day 5 pups or umbilical plasma from preeclamptic pregnancies, respectively. RESULTS: We report significant reduction in the area occupied by blood vessels in the motor and somatosensory brain cortex of offspring (postnatal day 5) from PELS compared with uncomplicated control offspring. These data were confirmed using 2 additional PELS models. Furthermore, circulating levels of critical proangiogenic factors, VEGF (vascular endothelial growth factor), and PlGF (placental growth factor) were lower in postnatal day 5 PELS. Also we found lower VEGF receptor 2 (KDR [kinase insert domain-containing receptor]) levels in mice and human endothelial cells exposed to the serum of postnatal day 5 PELS or fetal plasma of preeclamptic pregnancies, respectively. These changes were associated with lower in vitro angiogenic capacity, diminished cell migration, larger F-actin filaments, lower number of filopodia, and lower protein levels of F-actin polymerization regulators in brain endothelial cells exposed to serum or fetal plasma of offspring from preeclampsia. CONCLUSIONS: Offspring from preeclampsia exhibited diminished brain cortex angiogenesis, associated with lower circulating VEGF/PlGF/KDR protein levels, impaired brain endothelial migration, and dysfunctional assembly of F-actin filaments. These alterations may predispose to structural and functional alterations in long-term brain development.

Brain Vascular Dysfunction in Mothers and Their Children Exposed to Preeclampsia.

Preeclampsia is a maternal syndrome characterized by the new onset of hypertension and proteinuria after 20 weeks of gestation associated with multisystemic complications, including brain alterations. Indeed, brain complications associated with preeclampsia are the leading direct causes of fetal and maternal morbidity and mortality, especially in low- and middle-income countries. In addition to the well-recognized long-term adverse cardiovascular effects of preeclampsia, women who have had preeclampsia have higher risk of stroke, dementia, intracerebral white matter lesions, epilepsy, and perhaps also cognitive decline postpartum. Furthermore, increasing evidence has also associated preeclampsia with similar cognitive and cerebral disorders in the offspring. However, the mechanistic links between these associations remain unresolved. This article summarizes the current knowledge about the cerebrovascular complications elicited by preeclampsia and the potential pathophysiological mechanisms involved, emphasizing the impaired brain vascular function in the mother and their offspring.

Dysregulation of vascular endothelial growth factor receptor 2 phosphorylation is associated with disruption of the blood-brain barrier and brain endothelial cell apoptosis induced by plasma from women with preeclampsia.

Disruption of the blood-brain barrier (BBB) is central in the pathophysiology of acute cerebral complications in women who have preeclampsia. Underling mechanisms are unclear. Using female human brain endothelial cells as an in vitro model of BBB, we show that plasma of women with preeclampsia increases cell apoptosis and permeability via activation of the vascular endothelial growth factor receptor 2 (VEGFR2). Since plasma of women with preeclampsia also enhanced VEGFR2 phosphorylation in the tyrosine 951 but decreased phosphorylation at the tyrosine 1175, we propose the former would be the more likely active form of VEGFR2 responsible for BBB alterations.

Cerebral Biomarkers and Blood-Brain Barrier Integrity in Preeclampsia.

Cerebral complications in preeclampsia contribute substantially to maternal mortality and morbidity. There is a lack of reliable and accessible predictors for preeclampsia-related cerebral complications. In this study, plasma from women with preeclampsia (n = 28), women with normal pregnancies (n = 28) and non-pregnant women (n = 16) was analyzed for concentrations of the cerebral biomarkers neurofilament light (NfL), tau, neuron-specific enolase (NSE) and S100B. Then, an in vitro blood−brain barrier (BBB) model, based on the human cerebral microvascular endothelial cell line (hCMEC/D3), was employed to assess the effect of plasma from the three study groups. Transendothelial electrical resistance (TEER) was used as an estimation of BBB integrity. NfL and tau are proteins expressed in axons, NSE in neurons and S100B in glial cells and are used as biomarkers for neurological injury in other diseases such as dementia, traumatic brain injury and hypoxic brain injury. Plasma concentrations of NfL, tau, NSE and S100B were all higher in women with preeclampsia compared with women with normal pregnancies (8.85 vs. 5.25 ng/L, p < 0.001; 2.90 vs. 2.40 ng/L, p < 0.05; 3.50 vs. 2.37 µg/L, p < 0.001 and 0.08 vs. 0.05 µg/L, p < 0.01, respectively). Plasma concentrations of NfL were also higher in women with preeclampsia compared with non-pregnant women (p < 0.001). Higher plasma concentrations of the cerebral biomarker NfL were associated with decreased TEER (p = 0.002) in an in vitro model of the BBB, a finding which indicates that NfL could be a promising biomarker for BBB alterations in preeclampsia.

Disruption of the Blood-Brain Barrier by Extracellular Vesicles From Preeclampsia Plasma and Hypoxic Placentae: Attenuation by Magnesium Sulfate.

[Figure: see text].

SARS-CoV-2 (COVID-19) en gestación y placenta: una revisión narrativa sobre el estado del arte / SARS-CoV-2 (COVID-19) in pregnancy and placenta: a narrative review on state of the art

Resumen La crisis sanitaria por la pandemia de COVID-19, enfermedad generada por la infección con el SARS-CoV-2, ha llevado a la pérdida de más de 25,000 vidas en Chile, con más de 370,000 mujeres entre 15 y 44 años con infección confirmada. Se ha reportado una mayor vulnerabilidad de las mujeres gestantes en cuanto a desarrollar cuadros de COVID-19 graves o críticos, con un aumento de la incidencia de resultados obstétricos y perinatales adversos. Es relevante considerar que un alto porcentaje de las gestantes infectadas con SARS-CoV-2 son asintomáticas, lo cual nos pone en alerta en cuanto a que ciertos efectos del virus durante la gestación podrían no ser evidentes para la observación clínica. Se ha demostrado la presencia de SARS-CoV-2 en la placenta, asociándose la infección placentaria con alteraciones vasculares que podrían afectar el flujo útero-placentario. Por otro lado, la transmisión vertical al feto parece que es poco frecuente, pero factible. Se resumen las evidencias disponibles hasta el momento sobre los principales efectos de la COVID-19 en la gestación, con énfasis en los estudios sobre los efectos de la infección por SARS-CoV-2 en la placenta. El objetivo es relevar el tema, destacando que son diversas las preguntas que necesitan ser abordadas, considerando el impacto que esta pandemia podría tener sobre la salud gestacional.

Abstract In Chile, the COVID-19 pandemic, a disease induced by infection with SARS-CoV-2, has caused more than 25,000 deaths. More than 370,000 women between 15 and 44 years have been detected with the infection. The greater vulnerability of pregnant women has been reported, mainly related to a higher risk for severe or critical COVID-19, with an increased incidence of adverse obstetrics and perinatal outcomes. It is relevant to consider that a high percentage of pregnant women infected with SARS-CoV-2 are asymptomatic for COVID-19, which indicates that specific effects of the virus during pregnancy may not be evident from clinical observation. The presence of SARS-CoV-2 in the placenta has been demonstrated, associating placental infection with vascular alterations that could affect utero-placental flow. On the other hand, vertical transmission to the fetus is rare but feasible. This manuscript summarizes the evidence available to date on the main effects of COVID-19 in pregnancy, emphasizing studies about the impact of SARS-CoV-2 in the placenta. This review aims to promote this issue, highlighting that several questions need to be addressed, considering the effect this pandemic could have on gestational health.

Advantages in Wound Healing Process in Female Mice Require Upregulation A2A-Mediated Angiogenesis under the Stimulation of 17ß-Estradiol.

Estrogenic steroids and adenosine A2A receptors promote the wound healing and angiogenesis processes. However, so far, it is unclear whether estrogen may regulate the expression and pro-angiogenic activity of A2A receptors. Using in vivo analyses, we showed that female wild type (WT) mice have a more rapid wound healing process than female or male A2A-deficient mice (A2AKO) mice. We also found that pulmonary endothelial cells (mPEC) isolated from female WT mice showed higher expression of A2A receptor than mPEC from male WT mice. mPEC from female WT mice were more sensitive to A2A-mediated pro-angiogenic response, suggesting an ER and A2A crosstalk, which was confirmed using cells isolated from A2AKO. In those female cells, 17ß-estradiol potentiated A2A-mediated cell proliferation, an effect that was inhibited by selective antagonists of estrogen receptors (ER), ERα, and ERß. Therefore, estrogen regulates the expression and/or pro-angiogenic activity of A2A adenosine receptors, likely involving activation of ERα and ERß receptors. Sexual dimorphism in wound healing observed in the A2AKO mice process reinforces the functional crosstalk between ER and A2A receptors.

Deletion of the adenosine A2A receptor increases the survival rate in a mice model of polymicrobial sepsis.

We aim to investigate the role of A2A receptor in peritonitis-related sepsis by injection of a fecal solution (FS) as a model of polymicrobial infection. C57/black J6 wild-type (WT) and A2A-deficient mice (A2AKO) were exposed to sepsis induced by intraperitoneal injection of a FS (FS-induced peritonitis) or instead was injected with saline buffer (Sham). Survival rate and sepsis score were measured up to 48 h. The presence of bacteria in tissue homogenates was analyzed. Telemetry and speckle laser Doppler were used for systemic blood pressure and peripheral blood perfusion analysis, respectively. Histological analysis and identification of active caspase 3 were performed in selected organs, including the liver. The survival rate of A2AKO mice exposed to FS-induced peritonitis was significantly higher, and the sepsis score was lower than their respective WT counterpart. Injection of FS increases (50 to 150 folds) the number of colonies forming units in the liver, kidney, blood, and lung in WT mice, while these effects were significantly attenuated in A2AKO mice exposed to FS-induced peritonitis. A significant reduction in both systolic and diastolic blood pressure, as well as in the peripheral perfusion was observed in WT and A2AKO mice exposed to FS-induced peritonitis. Although, these last effects were significantly attenuated in A2AKO mice. Histological analysis showed a large perivascular infiltration of polymorphonuclear in the liver of WT and A2AKO mice exposed to FS-induced peritonitis, but again, this effect was attenuated in A2AKO mice. Finally, high expression of active caspase 3 was found only in the liver of WT mice exposed to FS-induced peritonitis. The absence of the A2A receptor increases the survival rate in mice exposed to polymicrobial sepsis. This outcome was associated with both hemodynamic compensation and enhanced anti-bacterial response.

Physiological response to eccentric and concentric cycling in patients with chronic obstructive pulmonary disease.

We aimed to compare the cardiorespiratory, metabolic, and perceptual responses to high- and moderate-intensity eccentric cycling versus moderate-intensity concentric cycling in chronic obstructive pulmonary disease (COPD) patients. Ten patients with moderate COPD (forced expiratory volume in 1 s (FEV1) = 68.6% ± 20.4% of predicted; 68.3 ± 9.1 years) performed 30 min of moderate-intensity concentric (CONC-M: 50% maximum workload; Wmax), moderate-intensity eccentric (ECC-M: 50% Wmax), and high-intensity eccentric (ECC-H: 100% Wmax) cycling. Average power output, oxygen consumption (V̇O2), minute ventilation (VE), respiratory frequency (fR), oxygen saturation (SpO2), heart rate (HR), systolic and diastolic blood pressure (SBP and DBP), rate of perceived exertion (RPE), and dyspnea were measured during cycling. Compared with CONC-M, lower V̇O2 (-52% ± 14%), VE (-47% ± 16%), fR (-21% ± 14%), HR (-14% ± 16%), SBP (-73% ± 54%), RPE (-36% ± 26%), and dyspnea (-41% ± 37%) were found during ECC-M. During ECC-H, a similar metabolic demand to CONC-M was found. However, average power output was 117% ± 79% higher during ECC-H. Eccentric cycling can be safely performed by COPD patients and induced lower cardiorespiratory, metabolic, and perceptual responses than concentric exercise when performed at the same workload. Novelty Moderate- and high-intensity eccentric cycling can be performed by COPD patients. Moderate-intensity eccentric cycling showed lower cardiorespiratory, metabolic, and perceptual demand than concentric cycling at the same workload in COPD patients. Even at double workload, eccentric cycling induces lower cardiorespiratory, metabolic, and perceptual demand than moderate-intensity concentric cycling.

Gestational diabetes mellitus is associated with increased pro-migratory activation of vascular endothelial growth factor receptor 2 and reduced expression of vascular endothelial growth factor receptor 1.

Placentas from gestational diabetes mellitus (GDM) are often hypervascularized; however, participation of vascular endothelial growth factor (VEGF) and its receptors in this placental adaptation is unclear. We aimed to test whether changes in phosphorylation of tyrosine 951 or tyrosine 1175 (pY951 or pY1175) of the vascular endothelial growth factor receptor 2 (KDR) are associated with the proangiogenic state observed in placentas from GDM. We obtained placental samples from women with normal pregnancies (n = 24) or GDM (n = 18). We measured the relative expression of markers for endothelial cell number (CD31, CD34), VEGF, vascular endothelial growth factor receptor 1 (Flt-1), KDR, pY951 and pY1175 of KDR in placental homogenate. Immunohistochemistry of placental blood vessels were performed using CD34. Proliferation and migration of human umbilical vein endothelial cells (HUVEC) obtained from normal pregnancy and GDM were determined in absence or presence of conditioned medium (CM) harvested from GDM or normoglycemic HUVEC cultures. GDM was associated with more CD31 and CD34 protein compared to normal pregnancy. High number, but reduced area of placental blood vessels was found in GDM. Reduced Flt-1 levels (mRNA and protein) are associated with reduced KDR mRNA, but higher KDR protein levels in placentas from GDM. No significant changes in Y951-or Y1175-phosphorylation of KDR in placentas from GDM were found. GDM did not alter proliferation of HUVECs, but enhanced migration. Conditioned medium harvested from GDM HUVEC cultures enhanced KDR protein amount, tube formation capacity and cell migration in HUVEC isolated from normoglycemic pregnancies. The data indicate that GDM is associated with reduced expression of Flt-1 but high pro-migratory activation of KDR reflecting a proangiogenic state in GDM.

Pro-angiogenic Role of Insulin: From Physiology to Pathology.

The underlying molecular mechanisms involve in the regulation of the angiogenic process by insulin are not well understood. In this review article, we aim to describe the role of insulin and insulin receptor activation on the control of angiogenesis and how these mechanisms can be deregulated in human diseases. Functional expression of insulin receptors and their signaling pathways has been described on endothelial cells and pericytes, both of the main cells involved in vessel formation and maturation. Consequently, insulin has been shown to regulate endothelial cell migration, proliferation, and in vitro tubular structure formation through binding to its receptors and activation of intracellular phosphorylation cascades. Furthermore, insulin-mediated pro-angiogenic state is potentiated by generation of vascular growth factors, such as the vascular endothelial growth factor, produced by endothelial cells. Additionally, diseases such as insulin resistance, obesity, diabetes, and cancer may be associated with the deregulation of insulin-mediated angiogenesis. Despite this knowledge, the underlying molecular mechanisms need to be elucidated in order to provide new insights into the role of insulin on angiogenesis.

Combinación de osteotecnia más conservación de músculos en montaje único de Canis lupus familiaris / Combination of osteotecnia and preservation of muscles in unique assembly of Canis lupus familiaris

Para la enseñanza de la Anatomía siempre se está en búsqueda de alternativas para la conservación y presentación de preparados anatómicos, realizando variaciones de diferentes técnicas, que permitan presentar especímenes con fines didácticos, para lograr un mejor aprendizaje, comprensión y motivación por la Morfología. El objetivo de este trabajo fue utilizar una combinación de osteotecnia más la conservación de músculos, en un montaje único que permite estudiar en una mitad el esqueleto, y en la otra, la musculatura superficial de un Canis lupus familiaris. Se utilizó un cadáver del especimen fijado por congelación, luego se realizó una limpieza general, extracción de vísceras y retiro de tegumentos previo al corte sagital. En la mitad derecha se realizó la limpieza de los huesos mediante ebullición combinada con métodos mecánicos y posteriormente, el desengrasado y blanqueado de ellos previo al ensamble del esqueleto. Para la conservación de músculos la mitad izquierda del cuerpo fue sumergida en "solución fijadora conservadora chilena" libre de formol, por 31 días, tras lo cual se realizó la disección de fascias y tejido graso para delimitar músculos superficiales. Una vez tratado cada segmento, se procedió al montaje combinado de las mitades en posición anatómica del espécimen, usando suturas desde craneal a caudal, sobre pedestales. La técnica utilizada de montaje combinado proporciona un material anatómico-didáctico flexible, de bajo costo y escasa toxicidad, con la potencialidad de permitir reforzar de manera interactiva el aprendizaje significativo de los estudiantes, facilitando la observación y estudio de la topografía de huesos y músculos.

The teaching of anatomy is always in search of alternatives for the preservation and presentation of anatomical preparations, doing variations of different techniques that allow to present specimens with didactic goals so as to get a better learning, comprehension and motivation for morphology. The purpose of this study was to use a combination of osteotecnia and the preservations of muscles in a unique assembly allowing to study half of the skeleton and, in the other, the superficial muscles of a Canis lupus familiaris. A corpse of the specimen was used, fixed by freezing; then, a general cleaning was carried out, extraction of viscera and removal of teguments before the sagittal cut. On the right half, using boiling combined with mechanical methods and, subsequently, their degreasing and bleaching, prior to the skeleton's assembly carried out the cleaning of the bones. For the preservation of muscles, the left half of the body was submerged in a "Chilean preserving and fixative solution" free from formaldehyde for 31 days, following the dissection of fascia and fatty tissue to delimit superficial muscles. Once each segment is treated, the combined assembly of the halves is made in anatomical position of the specimen, using stitches from cranial to caudal, over pedestals. The utilized technique of combined assembly provides a flexible didactic-anatomical material, of low-cost and low-toxicity, with the potentiality to allow reinforcing in an interactive way the meaningful learning of the students, making the observation easier as well as the study of topography of bones and muscles.

Adenosine A2A receptor regulates expression of vascular endothelial growth factor in feto-placental endothelium from normal and late-onset pre-eclamptic pregnancies.

We aim to investigate whether A2A/nitric oxide-mediated regulation of vascular endothelial growth factor (VEGF) expression is impaired in feto-placental endothelial cells from late-onset pre-eclampsia. Cultures of human umbilical vein endothelial cells (HUVECs) and human placental microvascular endothelial cells (hPMECs) from normal and pre-eclamptic pregnancies were used. Assays by using small interference RNA (siRNA) for A2A were performed, and transfected cells were used for estimation of messenger RNA (mRNA) levels of VEGF, as well as for cell proliferation and angiogenesis in vitro. CGS-21680 (A2A agonist, 24 h) increases HUVEC and hPMEC proliferation in a dose response manner. Furthermore, similar to CGS-21680, the nitric oxide donor, S-nitroso-N-acetyl-penicillamine oxide (SNAP), increased cell proliferation in a dose response manner (logEC50 10-9.2 M). In hPMEC, CGS-21680 increased VEGF protein levels in both normal (∼1.5-fold) and pre-eclamptic pregnancies (∼1.2-fold), an effect blocked by the A2A antagonist, ZM-241385 (10-5 M) and the inhibitor of NO synthase, N ω-nitro-L-arginine methyl ester hydrochloride (L-NAME). Subsequently, SNAP partially recovered cell proliferation and in vitro angiogenesis capacity of cells from normal pregnancies exposed to siRNA for A2A. CGS-21680 also increased (∼1.5-fold) the level of VEGF mRNA in HUVEC from normal pregnancies, but not in pre-eclampsia. Additionally, transfection with siRNA for A2A decrease (∼30 %) the level of mRNA for VEGF in normal pregnancy compared to untransfected cells, an effect partially reversed by co-incubation with SNAP. The A2A-NO-VEGF pathway is present in endothelium from microcirculation and macrocirculation in both normal and pre-eclamptic pregnancies. However, NO signaling pathway seems to be impaired in HUVEC from pre-eclampsia.

Role of Extracellular Vesicles and microRNAs on Dysfunctional Angiogenesis during Preeclamptic Pregnancies.

Preeclampsia is a syndrome characterized by hypertension during pregnancy, which is a leading cause of morbidity and mortality in both mother and newborn in developing countries. Some advances have increased the understanding of pathophysiology of this disease. For example, reduced utero-placental blood flow associated with impaired trophoblast invasion may lead to a hypoxic placenta that releases harmful materials into the maternal and feto-placental circulation and impairs endothelial function. Identification of these harmful materials is one of the hot topics in the literature, since these provide potential biomarkers. Certainty, such knowledge will help us to understand the miscommunication between mother and fetus. In this review we highlight how placental extracellular vesicles and their cargo, such as small RNAs (i.e., microRNAs), might be involved in endothelial dysfunction, and then in the angiogenesis process, during preeclampsia. Currently only a few reports have addressed the potential role of endothelial regulatory miRNA in the impaired angiogenesis in preeclampsia. One of the main limitations in this area is the variability of the analyses performed in the current literature. This includes variability in the size of the particles analyzed, and broad variation in the exosomes considered. The quantity of microRNA targets genes suggest that practically all endothelial cell metabolic functions might be impaired. More studies are required to investigate mechanisms underlying miRNA released from placenta upon endothelial function involved in the angiogenenic process.

Potential role of A2B adenosine receptors on proliferation/migration of fetal endothelium derived from preeclamptic pregnancies.

To investigate the functionality of A2B adenosine receptor (A2BAR) and the nitric oxide (NO) and vascular endothelial growth factor (VEGF) signaling pathway in the endothelial cell proliferation/migration during preeclampsia, we used human umbilical vein endothelial cells (HUVECs) isolated from normal pregnancies (n = 15) or pregnancies with preeclampsia (n = 15). Experiments were performed in presence or absence of the nonselective adenosine receptor agonist NECA, the A2BAR selective antagonist MRS-1754, and the nitric oxide synthase (NOS) inhibitor L-NAME. Results indicated that cells from preeclampsia exhibited a significant higher protein level of A2BAR and logEC50 for NECA-mediated proliferation than normotensive pregnancies. The stimulatory effect of NECA (10 µM, 24 h) on cell proliferation was prevented by MRS-1754 (5 nM) coincubation only in cells from normotensive pregnancies. Nevertheless, L-NAME (100 µM, 24 h) reduced the NECA-induced cell proliferation/migration in HUVEC from normal pregnancy; however in preeclampsia only NECA-induced cell proliferation was reduced by L-NAME. Moreover, NECA increased protein nitration and abundance of VEGF in cells from normal pregnancy and effect prevented by MRS-1754 coincubation. Nevertheless, in preeclampsia NECA did not affect the protein level of VEGF. In conclusion HUVECs from preeclampsia exhibit elevated protein level of A2BAR and impairment of A2BAR-mediated NO/VEGF signaling pathway.

Neurocitoma central: reporte de 2 casos / Central neurocytoma: report of 2 cases

El Neurocitoma Central (NC) es un tumor del SNC infrecuente, de estirpe neuronal, frecuentemente intraventricular, que generalmente afecta adultos jòvenes, tiene crecimiento lento y que al momento del diagnóstico tiene con frecuencia un volumen considerable. Su comportamiento es poco agresivo y una exéresis quirúrgica conservadora permite mejorar sustancialmente la calidad y espectativa vital. Presentamos aquí dos casos clínicos de pacientes con cuadros clínicos compatibles a los decritos en la literatura. Se realizaron estudios inmunohistoquímicos de las lesiones que confirman el diagnóstico.

Central Neurocytoma (CN) it's a rare Central Nervous System Tumor, derivated of the neuron, frequently intraventricular, it generally affects young adults, has a slow pattern of growth and at diagnosis is frequently voluminous. It's a less aggressive kind of tumor and a conservative surgery exeresis allows a better quality and expectative of life. We present two cases of patients with similar clinical presentation with the descriptions find in the literature and with histologyc and immunohistochemistry studies that confirms the diagnosis.