Angiopoietins Modulate Survival, Migration, and the Components of the Ang-Tie2 Pathway of Chronic Lymphocytic Leukaemia (CLL) Cells In Vitro

In actuality, chronic lymphocytic leukaemia (CLL) remains an incurable haematopoietic malignancy of high prevalence amongst elderly populations in the West. Malignant CLL cells characteristically accumulate in the peripheral blood, bone marrow, lymph nodes, and spleen of CLL patients. There is evidence that CLL cells express Ang2 and Tie1, two central components of the Ang-Tie2 pro-angiogenic pathway. Central to blood vessel development and maintenance, at present it remains unclear how the Ang-Tie2 pathway modulates CLL pathophysiology. Here we evaluate the status of the Ang-Tie2 pathway in CLL cells and assess Ang1 levels in plasma/cell medium from CLL samples. To understand how angiopoietins in the microenvironment regulate the components of Ang-Tie2 pathway, survival, migration, and metabolic fitness of CLL cells, we exposed CLL cells to recombinant angiopoietins. CLL plasma and CLL cells in culture present significant lower levels of Ang1. CLL cells simultaneously express Ang1, Ang2, and Tie1 mRNA, but lack that of Tie2 and its regulator, VE-PTP. Exposure to Ang1 confers survival advantage in the long-term, whereas Ang2 and trebananib, an angiopoietin blocker, proved detrimental. Angiopoietins differentially modulate expression of Ang1, Ang2, and Tie1 transcripts. Ang2, but not Ang1, induces the concomitant and transient expression of Tie2 and VE-PTP mRNA. Both angiopoietins, particularly Ang2, increase CLL-Tie1 expression and Ang1 clearly induces chemotaxis and transendothelial-like migration of CLL cells. Besides, changes in caspase and ATP content corroborate the sensitivity of CLL cells to angiopoietin exposure. Altogether, this work shows that angiopoietins regulate the fate of CLL cells in a Tie2-independent manner and highlights the potential of the Ang-Tie2 pathway as a therapeutic target in CLL research

Angiogenic factors in chronic lymphocytic leukaemia (CLL): Where do we stand?

The role of angiogenesis in haematological malignancies such as chronic lymphocytic leukaemia (CLL) is difficult to envision, because leukaemia cells are not dependent on a network of blood vessels to support basic physiological requirements. Regardless, CLL cells secrete high levels of major angiogenic factors, such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and platelet derived growth factor (PDGF). Nonetheless, it remains unclear how most angiogenic factors regulate accumulation and delayed apoptosis of CLL cells. Angiogenic factors such as leptin, granulocyte colony-stimulating factor (G-CSF), follistatin, angiopoietin-1 (Ang1), angiogenin (ANG), midkine (MK), pleiotrophin (PTN), progranulin (PGRN), proliferin (PLF), placental growth factor (PIGF), and endothelial locus-1 (Del-1), represent novel therapeutic targets of future CLL research but have remained widely overlooked. This review aims to outline our current understanding of angiogenic growth factors and their relationship with CLL, a still uncured haematopoietic malignancy. (C) 2014 Elsevier Ireland Ltd. All rights reserved

Libro de Proyectos Finales 2021 primer semestre

PregradoIngeniero CivilIngeniero de SistemasIngeniero ElectricistaIngeniero ElectrónicoIngeniero IndustrialIngeniero Mecánic

Neotropical freshwater fisheries : A dataset of occurrence and abundance of freshwater fishes in the Neotropics

The Neotropical region hosts 4225 freshwater fish species, ranking first among the world's most diverse regions for freshwater fishes. Our NEOTROPICAL FRESHWATER FISHES data set is the first to produce a large-scale Neotropical freshwater fish inventory, covering the entire Neotropical region from Mexico and the Caribbean in the north to the southern limits in Argentina, Paraguay, Chile, and Uruguay. We compiled 185,787 distribution records, with unique georeferenced coordinates, for the 4225 species, represented by occurrence and abundance data. The number of species for the most numerous orders are as follows: Characiformes (1289), Siluriformes (1384), Cichliformes (354), Cyprinodontiformes (245), and Gymnotiformes (135). The most recorded species was the characid Astyanax fasciatus (4696 records). We registered 116,802 distribution records for native species, compared to 1802 distribution records for nonnative species. The main aim of the NEOTROPICAL FRESHWATER FISHES data set was to make these occurrence and abundance data accessible for international researchers to develop ecological and macroecological studies, from local to regional scales, with focal fish species, families, or orders. We anticipate that the NEOTROPICAL FRESHWATER FISHES data set will be valuable for studies on a wide range of ecological processes, such as trophic cascades, fishery pressure, the effects of habitat loss and fragmentation, and the impacts of species invasion and climate change. There are no copyright restrictions on the data, and please cite this data paper when using the data in publications

Efficacy and adverse events profile of videolaryngoscopy in critically ill patients: subanalysis of the INTUBE study

Background: Tracheal intubation is a high-risk procedure in the critically ill, with increased intubation failure rates and a high risk of other adverse events. Videolaryngoscopy might improve intubation outcomes in this population, but evidence remains conflicting, and its impact on adverse event rates is debated.Methods: This is a subanalysis of a large international prospective cohort of critically ill patients (INTUBE Study) performed from 1 October 2018 to 31 July 2019 and involving 197 sites from 29 countries across five continents. Our primary aim was to determine the first-pass intubation success rates of videolaryngoscopy. Secondary aims were characterising (a) videolaryngoscopy use in the critically ill patient population and (b) the incidence of severe adverse effects compared with direct laryngoscopy.Results: Of 2916 patients, videolaryngoscopy was used in 500 patients (17.2%) and direct laryngoscopy in 2416 (82.8%). First-pass intubation success was higher with videolaryngoscopy compared with direct laryngoscopy (84% vs 79%, P1/40.02). Patients undergoing videolaryngoscopy had a higher frequency of difficult airway predictors (60% vs 40%, P<0.001). In adjusted analyses, videolaryngoscopy increased the probability of first-pass intubation success, with an OR of 1.40 (95% confidence interval [CI] 1.05-1.87). Videolaryngoscopy was not significantly associated with risk of major adverse events (odds ratio 1.24, 95% CI 0.95-1.62) or cardiovascular events (odds ratio 0.78, 95% CI 0.60-1.02).Conclusions: In critically ill patients, videolaryngoscopy was associated with higher first-pass intubation success rates, despite being used in a population at higher risk of difficult airway management. Videolaryngoscopy was not associated with overall risk of major adverse events

Intubation Practices and Adverse Peri-intubation Events in Critically Ill Patients from 29 Countries

Importance: Tracheal intubation is one of the most commonly performed and high-risk interventions in critically ill patients. Limited information is available on adverse peri-intubation events. Objective: To evaluate the incidence and nature of adverse peri-intubation events and to assess current practice of intubation in critically ill patients. Design, Setting, and Participants: The International Observational Study to Understand the Impact and Best Practices of Airway Management in Critically Ill Patients (INTUBE) study was an international, multicenter, prospective cohort study involving consecutive critically ill patients undergoing tracheal intubation in the intensive care units (ICUs), emergency departments, and wards, from October 1, 2018, to July 31, 2019 (August 28, 2019, was the final follow-up) in a convenience sample of 197 sites from 29 countries across 5 continents. Exposures: Tracheal intubation. Main Outcomes and Measures: The primary outcome was the incidence of major adverse peri-intubation events defined as at least 1 of the following events occurring within 30 minutes from the start of the intubation procedure: cardiovascular instability (either: systolic pressure <65 mm Hg at least once, <90 mm Hg for >30 minutes, new or increase need of vasopressors or fluid bolus >15 mL/kg), severe hypoxemia (peripheral oxygen saturation <80%) or cardiac arrest. The secondary outcomes included intensive care unit mortality. Results: Of 3659 patients screened, 2964 (median age, 63 years; interquartile range [IQR], 49-74 years; 62.6% men) from 197 sites across 5 continents were included. The main reason for intubation was respiratory failure in 52.3% of patients, followed by neurological impairment in 30.5%, and cardiovascular instability in 9.4%. Primary outcome data were available for all patients. Among the study patients, 45.2% experienced at least 1 major adverse peri-intubation event. The predominant event was cardiovascular instability, observed in 42.6% of all patients undergoing emergency intubation, followed by severe hypoxemia (9.3%) and cardiac arrest (3.1%). Overall ICU mortality was 32.8%. Conclusions and Relevance: In this observational study of intubation practices in critically ill patients from a convenience sample of 197 sites across 29 countries, major adverse peri-intubation events - in particular cardiovascular instability - were observed frequently