Search results for "ngos"
showing 10 items of 115 documents
Synthesis and biological evaluation of sphingosine kinase 2 inhibitors with anti-inflammatory activity.
2019
The synthesis of inhibitors of SphK2 with novel structural scaffolds is reported. These compounds were designed from a molecular modeling study, in which the molecular interactions stabilizing the different complexes were taken into account. Particularly interesting is that 7‐bromo‐2‐(2‐phenylethyl)‐2,3,4,5‐tetrahydro‐1,4‐epoxynaphtho[1,2‐b]azepine, which is a selective inhibitor of SphK2, does not exert any cytotoxic effects and has a potent anti‐inflammatory effect. It was found to inhibit mononuclear cell adhesion to the dysfunctional endothelium with minimal impact on neutrophil–endothelial cell interactions. The information obtained from our theoretical and experimental study can be us…
Fingolimod as a Treatment in Neurologic Disorders Beyond Multiple Sclerosis
2020
Abstract Fingolimod is an approved treatment for relapsing–remitting multiple sclerosis (MS), and its properties in different pathways have raised interest in therapy research for other neurodegenerative diseases. Fingolimod is an agonist of sphingosine-1-phosphate (S1P) receptors. Its main pharmacologic effect is immunomodulation by lymphocyte homing, thereby reducing the numbers of T and B cells in circulation. Because of the ubiquitous expression of S1P receptors, other effects have also been described. Here, we review preclinical experiments evaluating the effects of treatment with fingolimod in neurodegenerative diseases other than MS, such as Alzheimer’s disease or epilepsy. Fingolimo…
A sphingosine kinase inhibitor combined with temozolomide induces glioblastoma cell death through accumulation of dihydrosphingosine and dihydroceram…
2014
AbstractGlioblastomas (GBMs) are very aggressive tumors with low chemosensitivity. The DNA-alkylating agent temozolomide (TMZ) is currently the most efficient chemotoxic drug for GBM therapy; however, many patients develop resistance to TMZ. Combining TMZ with another agent could present an improved treatment option if it could overcome TMZ resistance and avoid side effects. Sphingosine kinase inhibitors (SKIs) have emerged as anticancer agents. Sphingosine kinases are often overexpressed in tumors where their activity of phosphorylating sphingosine (Sph) contributes to tumor growth and migration. They control the levels of the pro-apoptotic ceramide (Cer) and Sph and of the pro-survival sp…
Non-governmental organizations in regional conflict prevention : a case study of the African Union's Continental Early Warning System
2007
NGO Legitimacy as a Continuous Negotiation Process : Fostering ‘Good Citizenship’ in Western Uganda
2022
The article draws on and contributes to debates on the legitimacy of non-governmental organizations (NGOs) engaged in development, defining organizational legitimacy as a social construct that is continually negotiated in relationships with diverse audiences. To explore the negotiated nature of NGO legitimacy, the article examines the efforts of a Ugandan NGO, Kabarole Research and Resource Centre (KRC), to foster citizens’ capacities in rural communities in the western part of the country. Drawing on interviews and participant observation, we scrutinize the ways in which KRC balances between different and even contrasting legitimacy expectations stemming from three types of encounters sign…
Reproductive outcomes after expectant and surgical management for tubal pregnancy: a retrospective study
2023
Background: The management of ectopic pregnancy is widely debated. Salpingectomy, salpingostomy, and expectant management are widely performed, but the best approach in terms of keeping good future spontaneous fertility chances is yet to be determined. Material and methods: We performed a retrospective analysis (Clinical Trial ID: NCT05479786) of the medical records of patients with an ultrasonographic or surgical diagnosis of tubal ectopic pregnancy that were admitted to the University of Debrecen Clinical Centre between 2012 and 2020. Results: A total of 312 patients were included in the analysis. Patients managed expectantly and patients treated with salpingostomy had significantly highe…
The sphingosine kinase 1 activator, K6PC-5, attenuates Ebola virus infection
2021
Summary Ebola virus (EBOV) is responsible for outbreaks with case fatality rates of up to 90% and for an epidemic in West Africa with more than ten thousand deaths. EBOV glycoprotein (EBOV-GP) is the only viral surface protein and is responsible for viral entry into cells. Here, by employing pseudotyped EBOV-GP viral particles, we uncover a critical role for sphingolipids in inhibiting viral entry. Sphingosine kinase 1 (SphK1) catalyzes the phosphorylation of sphingosine to sphingosine 1-phosphate (S1P). The administration of the SphK1 activator, K6PC-5, or S1P, or the overexpression of SphK1 consistently exhibited striking inhibitory effects in EBOV-GP-driven entry in diverse cell lines. F…
Difficult tracheal intubation in neonates and infants. NEonate and Children audiT of Anaesthesia pRactice IN Europe (NECTARINE)
2021
Background: Neonates and infants are susceptible to hypoxaemia in the perioperative period. The aim of this study was to analyse interventions related to anaesthesia tracheal intubations in this European cohort and identify their clinical consequences. Methods: We performed a secondary analysis of tracheal intubations of the European multicentre observational trial (NEonate and Children audiT of Anaesthesia pRactice IN Europe [NECTARINE]) in neonates and small infants with difficult tracheal intubation. The primary endpoint was the incidence of difficult intubation and the related complications. The secondary endpoints were the risk factors for severe hypoxaemia attributed to difficult airw…
Heterotheca subaxilaris (Compositae), nuevo xenófito para la flora ibérica
2017
Heterotheca subaxillaris (Compositae), a new xenophyte for the iberian flora. A first reference on the presence of Heterotheca subaxillaris (Lam.) Britton & Rusby (Compositae), native of North America, in the iberian flora is provided. This species has been located at the CV-10 highway, in la Pobla Tornesa, Castellón province (Spain).
Sphingosine-1-phosphate increases human alveolar epithelial IL-8 secretion, proliferation and neutrophil chemotaxis
2009
Sphingosine-1-phosphate (S1P) has been presented recently as a pro-inflammatory agent in the airway epithelium since S1P levels are increased in bronchoalveolar lavage fluid of human asthmatics. However, the effects of S1P over the alveolar epithelium and neutrophil interactions are poorly understood. Here, we show that S1P increased interleukin 8 (IL-8) gene expression and protein secretion and proliferation in alveolar epithelial cells A549 at physiological concentrations (1 microM). At the same time, S1P increased intracellular Ca2+ concentration (potency 17.91 microM, measured by epifluorescence microscopy), phospholipase D (PLD) activity (measured by chemiluminiscence method) and extra…