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  • Key words Erythropoietin  (1)
  • angiogenesis  (1)
  • 2000-2004  (2)
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  • 2000-2004  (2)
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  • 1
    ISSN: 1439-6327
    Keywords: Key words Erythropoietin ; Erythropoiesis ; Hypoxia ; Hypobaric chamber ; Altitude
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study aimed to determine whether brief hypoxic stimuli in a hypobaric chamber are able to elicit erythropoietin (EPO) secretion, and to effectively stimulate erythropoiesis in the short term. In two different experiments, a set of haematological, biochemical, haemorheological, aerobic performance, and medical tests were performed in two groups of healthy subjects. In the first experiment, the mean plasma concentration of EPO ([EPO]) increased from 8.7 to 13.5 mU · ml−1 (55.2%; P 〈 0.01) after 90 min of acute exposure at 540 hPa, and continued to rise until a peak was attained 3 h after the termination of hypoxia. In the second experiment, in which subjects were exposed to a simulated altitude of up to 5500 m (504 hPa) for 90 min, three times a week for 3 weeks, all haematological indicators of red cell mass increased significantly, reaching the highest mean values at the end of the programme or during the subsequent 2 weeks, including packed cell volume (from 42.5 to 45.1%; P 〈 0.01), red blood cell count (from 4.55 × 106 to 4.86 × 106 · l−1; P 〈 0.01), reticulocytes (from 0.5 to 1.4%; P 〈 0.01), and haemoglobin concentration (from 14.3 to 16.2 g · dl−1; P 〈 0.01), without an increase in blood viscosity. Arterial blood oxygen saturation during hypoxia was improved (from 60% to 78%; P 〈 0.05). Our most relevant finding is the ability to effectively stimulate erythropoiesis through brief intermittent hypoxic stimuli (90 min), in a short period of time (3 weeks), leading to a lower arterial blood desaturation in hypoxia. The proposed mechanism for these haematological and functional adaptations is the repeated triggering effect of EPO production caused by the intermittent hypoxic stimuli.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Cancer and metastasis reviews 19 (2000), S. 139-145 
    ISSN: 1573-7233
    Keywords: VEGF ; MAP kinases ; hypoxia ; angiogenesis ; growth control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Vascular endothelial growth factor (VEGF), a potent cytokine secreted by virtually all cells plays a key role in tumor angiogenesis. Disruption of one VEGF allele in mice has revealed a dramatic lethal effect in early embryogenesis, suggesting a very tight regulation of this gene. This commentary reviews the mechanisms whereby VEGF mRNA is controlled within the tumor environment by hypoxia and the MAP kinase signaling cascades. Using hamster fibroblasts as a cellular model, we demonstrated that the Ras-mediated activation of p42/p44 MAP kinases exerts a prominent action at the transcriptional level. In normoxic conditions, p42/p44 MAPKs activate the VEGF promoter at the proximal (−88/−66) region where Sp1/AP-2 transcriptional factor complexes are recruited. At low O2 tension, the stabilized and nuclear hypoxia inducible factor-1α (HIF-1α) is directly phosphorylated by p42/p44 MAPKs, an action which enhances HIF-1-dependent transcriptional activition of VEGF. In addition, MAPKs activated under various cellular stresses (p38MAPK and JNK), contribute to the increased expression of this angiogenic growth and survival factor by stabilizing the VEGF mRNA.
    Type of Medium: Electronic Resource
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