High Altitude Pregnancies and Vascular Dysfunction: Observations From Latin American Studies.
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ABSTRACT:
SUBMITTER: Gonzalez-Candia A
PROVIDER: S-EPMC8688922 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundPeak inspiratory and expiratory flows (PIF, PEF) are parameters used to evaluate the mechanics of the respiratory system. These parameters can vary based on whether they are measured using mechanical devices vs. spirometry and based on the barometric pressure at which the measurements are obtained. Our objectives were (1) to report the normal values and variability of PEF and PIF of a Latin American population living at a moderate altitude (2240 m above sea level), (2) to analyze the adjustment of reference values obtained at sea level with those obtained in healthy subjects living at a moderate altitude, and (3) to assess the correlation between PEF obtained by spirometry (PEFs) and PEF obtained by mechanical devices (PEFm).MethodsIn this prospective and transversal study, men and women with good respiratory health aged between 2.8 and 68 years old were invited to participate. Randomly, they underwent spirometry (to measure PEFs and PIFs) and mechanical flowmetry (to measure PEFm).ResultsA total of 314 subjects participated, with an average age of 24.3 ± 16.4 years; 59% were Women. The main determinants for the reference equations were age, weight, height and sex at birth. The agreement of the PEFm, PEFs and PIFs values was inconsistent with that reported by other authors, even at the same barometric pressure. The association between PEFm and PEFs was r = 0.91 (p < 0.001), and the correlation coefficient of concordance was 0.84.ConclusionsThe PEFm, PEFs, and PIFs measurements in individuals living at moderate altitudes are different from those found by other authors in cities with different barometric pressures and ethnicities.
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Project description:We conducted a targeted genomic analysis using next-generation sequencing techniques in 70 Chilean patients with high-grade gliomas from a national single-center referral institution. We focused on relevant molecular markers such as mutations in isocitrate dehydrogenase 1/2 (IDH), telomerase reverse transcriptase promoter (TERTp), histone 3 (H3) gene family, TP53 and PTEN, epidermal growth factor receptor (EGFR) gene amplification, and cyclin-dependent kinase inhibitor 2A (CDKN2A) deletions. Survival analyses were performed to assess the clinical relevance and their impact on patient prognosis. Additionally, we explored the endoplasmic reticulum stress-related gene ERN1 due to its potential role in high-grade gliomas. This study underscores the importance of glioblastoma research in underrepresented populations, providing insights into high-grade gliomas molecular characteristics within Latin America. Our findings contribute to the growing evidence suggesting molecular diversity across glioblastoma populations, offering a foundation for future international comparative studies.
2024-06-30 | GSE252870 | GEO
Project description:Placental vascularization is a tightly regulated physiological process in which the maternal immune system plays a fundamental role. Vascularization of the maternal-placental interface involves a wide range of mechanisms primarily orchestrated by the fetal extravillous trophoblast and maternal immune cells. In a healthy pregnancy, an immune cross-talk between the mother and fetal cells results in the secretion of immunomodulatory mediators, apoptosis of specific cells, cellular differentiation/proliferation, angiogenesis, and vasculogenesis, altogether favoring a suitable microenvironment for the developing embryo. In the context of vasculopathy underlying common pregnancy disorders, it is believed that inefficient invasion of extravillous trophoblast cells in the endometrium leads to a poor placental blood supply, which, in turn, leads to decreased secretion of angiogenic factors, hypoxia, and inflammation commonly associated with preterm delivery, intrauterine growth restriction, and preeclampsia. In this review, we will focus on studies published by Latin American research groups, providing an extensive review of the role of genetic variants from candidate genes involved in a broad spectrum of biological processes underlying the pathophysiology of preeclampsia. In addition, we will discuss how these studies contribute to fill gaps in the current understanding of preeclampsia. Finally, we discuss some trending topics from important fields associated with pregnancy vascular disorders (e.g., epigenetics, transplantation biology, and non-coding RNAs) and underscore their possible implications in the pathophysiology of preeclampsia. As a result, these efforts are expected to give an overview of the extent of scientific research produced in Latin America and encourage multicentric collaborations by highlighted regional research groups involved in preeclampsia investigation.
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Project description:High-altitude (>2,500 m) residence increases the incidence of intrauterine growth restriction (IUGR) due, in part, to reduced uterine artery blood flow and impaired myometrial artery (MA) vasodilator response. A role for the AMP-activated protein kinase (AMPK) pathway in protecting against hypoxia-associated IUGR is suggested by genomic and transcriptomic studies in humans and functional studies in mice. AMPK is a hypoxia-sensitive metabolic sensor with vasodilatory properties. Here we hypothesized that AMPK-dependent vasodilation was increased in MAs from high versus low-altitude (<1,700 m) Colorado women with appropriate for gestational age (AGA) pregnancies and reduced in IUGR pregnancies regardless of altitude. Vasoreactivity studies showed that, in AGA pregnancies, MAs from high-altitude women were more sensitive to vasodilation by activation of AMPK with A769662 due chiefly to increased endothelial nitric oxide production, whereas MA responses to AMPK activation in the low-altitude women were endothelium independent. MAs from IUGR compared with AGA pregnancies had blunted vasodilator responses to acetylcholine at high altitude. We concluded that 1) blunted vasodilator responses in IUGR pregnancies confirm the importance of MA vasodilation for normal fetal growth and 2) the increased sensitivity to AMPK activation in AGA pregnancies at high altitude suggests that AMPK activation helped maintain MA vasodilation and fetal growth. These results highlight a novel mechanism for vasodilation of MAs under conditions of chronic hypoxia and suggest that AMPK activation could provide a therapy for increasing uteroplacental blood flow and improving fetal growth in IUGR pregnancies.NEW & NOTEWORTHY Intrauterine growth restriction (IUGR) impairs infant well- being and increases susceptibility to later-in-life diseases for mother and child. Our study reveals a novel role for AMPK in vasodilating the myometrial artery (MA) from women residing at high altitude (>2,500 m) with appropriate for gestational age pregnancies but not in IUGR pregnancies at any altitude.
| S-EPMC7474441 | biostudies-literature
Project description:Background Recent data about clinical features, triggers and management of anaphylaxis in Latin America is lacking. Objective To provide updated and extended data on anaphylaxis in this region. Method An online questionnaire was used, with 67 allergy units involved from 12 Latin-American countries and Spain. Among data recorded, demographic information, clinical features, severity, triggering agents, and treatment were received. Results Eight hundred and seventeen anaphylactic reactions were recorded. No difference in severity, regardless of pre-existing allergy or asthma history was found. Drug induced anaphylaxis (DIA) was most frequent (40.6%), followed by food induced anaphylaxis (FIA) (32.9%) and venom induced anaphylaxis (VIA) (12%). FIA and VIA were more common in children-adolescents. Non-steroidal anti-inflammatory drugs (NSAIDs) and beta-lactam antibiotics (BLA) were the most frequent drugs involved. Milk (61.1% of FIA) and egg (15.4% of FIA) in children, and shellfish (25.5% of FIA), fresh fruits (14.2% of FIA), and fish (11.3% of FIA) in adults were the most common FIA triggers. Fire ants were the most frequent insect triggers, and they induced more severe reactions than triggers of FIA and DIA (p < 0.0001). Epinephrine was used in 43.8% of anaphylaxis episodes. After Emergency Department treatment, epinephrine was prescribed to 13% of patients. Conclusions Drugs (NSAIDs and BLA), foods (milk and egg in children and shellfish, fruits and fish in adults) and fire ants were the most common inducers of anaphylaxis. Epinephrine was used in less than half of the episodes emphasizing the urgent need to improve dissemination and implementation of anaphylaxis guidelines.
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Project description:In the spring of 2017 an ER-2 aircraft campaign was undertaken over continental United States to observe energetic radiation from thunderstorms and lightning. The payload consisted of a suite of instruments designed to detect optical signals, electric fields, and gamma rays from lightning. Starting from Georgia, USA, 16 flights were performed, for a total of about 70 flight hours at a cruise altitude of 20 km. Of these, 45 flight hours were over thunderstorm regions. An analysis of two gamma ray glow events that were observed over Colorado at 21:47 UT on 8 May 2017 is presented. We explore the charge structure of the cloud system, as well as possible mechanisms that can produce the gamma ray glows. The thundercloud system we passed during the gamma ray glow observation had strong convection in the core of the cloud system. Electric field measurements combined with radar and radio measurements suggest an inverted charge structure, with an upper negative charge layer and a lower positive charge layer. Based on modeling results, we were not able to unambiguously determine the production mechanism. Possible mechanisms are either an enhancement of cosmic background locally (above or below 20 km) by an electric field below the local threshold or an enhancement of the cosmic background inside the cloud but then with normal polarity and an electric field well above the Relativistic Runaway Electron Avalanche threshold.
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Project description:Arbuscular mycorrhizal fungi (AMF) and dark septate endophytes (DSE) form symbiotic relationships with plants influencing their productivity, diversity and ecosystem functions. Only a few studies on these fungi, however, have been conducted in extreme elevations and none over 5500?m a.s.l., although vascular plants occur up to 6150?m a.s.l. in the Himalayas. We quantified AMF and DSE in roots of 62 plant species from contrasting habitats along an elevational gradient (3400-6150?m) in the Himalayas using a combination of optical microscopy and next generation sequencing. We linked AMF and DSE communities with host plant evolutionary history, ecological preferences (elevation and habitat type) and functional traits. We detected AMF in elevations up to 5800?m, indicating it is more constrained by extreme conditions than the host plants, which ascend up to 6150?m. In contrast, DSE were found across the entire gradient up to 6150?m. AMF diversity was unimodally related to elevation and positively related to the intensity of AMF colonization. Mid-elevation steppe and alpine plants hosted more diverse AMF communities than plants from deserts and the subnival zone. Our results bring novel insights to the abiotic and biotic filters structuring AMF and DSE communities in the Himalayas.
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Project description:The anti-inflammatory and antioxidant effects of exendin-4 (Ex-4) have been reported previously. However, whether (Ex-4) has anti-inflammatory and antioxidant effects on high-altitude cerebral edema (HACE) remains poorly understood. In this study, two rat models of HACE were established by placing rats in a hypoxic environment with a simulated altitude of either 6000- or 7000-m above sea level (MASL) for 72 hours. An altitude of 7000 MASL with 72-hours of hypoxia was found to be the optimized experimental paradigm for establishing HACE models. Then, in rats where a model of HACE was established by introducing them to a 7000 MASL environment with 72-hours of hypoxia treatment, 2, 10 and, 100 ?g of Ex-4 was intraperitoneally administrated. The open field test and tail suspension test were used to test animal behavior. Routine methods were used to detect change in inflammatory cells. Hematoxylin-eosin staining was performed to determine pathological changes to brain tissue. Wet/dry weight ratios were used to measure brain water content. Evans blue leakage was used to determine blood-brain barrier integrity. Enzyme-linked immunosorbent assay (ELISA) was performed to measure markers of inflammation and oxidative stress including superoxide dismutase, glutathione, and malonaldehyde values, as well as interleukin-6, tumor necrosis factor-alpha, cyclic adenosine monophosphate levels in the brain tissue. Western blot analysis was performed to determine the levels of occludin, ZO-1, SOCS-3, vascular endothelial growth factor, EPAC1, nuclear factor-kappa B, and aquaporin-4. Our results demonstrate that Ex-4 preconditioning decreased brain water content, inhibited inflammation and oxidative stress, alleviated brain tissue injury, maintain blood-brain barrier integrity, and effectively improved motor function in rat models of HACE. These findings suggest that Ex-4 exhibits therapeutic potential in the treatment of HACE.
| S-EPMC5950675 | biostudies-literature
Project description:BackgroundHigh-altitude cerebral edema (HACE) is a serious and potentially fatal brain injury that is caused by acute hypobaric hypoxia (HH) exposure. Vasogenic edema is the main pathological factor of this condition. Hypoxia-induced disruptions of tight junctions in the endothelium trigger blood‒brain barrier (BBB) damage and induce vasogenic edema. Nuclear respiratory factor 1 (NRF1) acts as a major regulator of hypoxia-induced endothelial cell injury, and caveolin-1 (CAV-1) is upregulated as its downstream gene in hypoxic endothelial cells. This study aimed to investigate whether CAV-1 is involved in HACE progression and the underlying mechanism.MethodsC57BL/6 mice were exposed to HH (7600 m above sea level) for 24 h, and BBB injury was assessed by brain water content, Evans blue staining and FITC-dextran leakage. Immunofluorescence, transmission electron microscope, transendothelial electrical resistance (TEER), transcytosis assays, and western blotting were performed to confirm the role and underlying mechanism of CAV-1 in the disruption of tight junctions and BBB permeability. Mice or bEnd.3 cells were pretreated with MβCD, a specific blocker of CAV-1, and the effect of CAV-1 on claudin-5 internalization under hypoxic conditions was detected by immunofluorescence, western blotting, and TEER. The expression of NRF1 was knocked down, and the regulation of CAV-1 by NRF1 under hypoxic conditions was examined by qPCR, western blotting, and immunofluorescence.ResultsThe BBB was severely damaged and was accompanied by a significant loss of vascular tight junction proteins in HACE mice. CAV-1 was significantly upregulated in endothelial cells, and claudin-5 explicitly colocalized with CAV-1. During the in vitro experiments, hypoxia increased cell permeability, CAV-1 expression, and claudin-5 internalization and downregulated tight junction proteins. Simultaneously, hypoxia induced the upregulation of CAV-1 by activating NRF1. Blocking CAV-1-mediated intracellular transport improved the integrity of TJs in hypoxic endothelial cells and effectively inhibited the increase in BBB permeability and brain water content in HH animals.ConclusionsHypoxia upregulated CAV-1 transcription via the activation of NRF1 in endothelial cells, thus inducing the internalization and autophagic degradation of claudin-5. These effects lead to the destruction of the BBB and trigger HACE. Therefore, CAV-1 may be a potential therapeutic target for HACE. Video abstract.
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Project description:High-altitude pulmonary edema occurs most frequently in non-acclimatized low landers on exposure to altitude ?2500?m. High-altitude pulmonary edema is a complex condition that involves perturbation of signaling pathways in vasoconstrictors, vasodilators, anti-diuretics, and vascular growth factors. Genetic variations are instrumental in regulating these pathways and evidence is accumulating for a role of epigenetic modification in hypoxic responses. This review focuses on the crosstalk between high-altitude pulmonary edema-associated genetic variants and transcription factors, comparing high-altitude adapted and high-altitude pulmonary edema-afflicted subjects. This approach might ultimately yield biomarker information both to understand and to design therapies for high-altitude adaptation.
| S-EPMC7682230 | biostudies-literature