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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Peptides are of potential interest in the field of gene therapy but require modification by genetic engineering to facilitate their secretion. Amino terminal addition of a signal peptide is not always sufficient to achieve this goal, as found in this study for β-endorphin. To overcome this problem, addition of the pre-pro-sequence of mouse nerve growth factor to β-endorphin was tested. Retrovirus-mediated expression of a hybrid construct of the pre-pro-sequence of nerve growth factor and human β-endorphin in primary fibroblasts resulted in the secretion of β-endorphin immunoreactivity at a rate of 620 pg/h/106 cells. Analysis of the secreted β-endorphin immunoreactivity with reverse-phase HPLC, immunoassays using three different antibodies, and an assay for the specific displacement of [3H][d-Ala2,N-MePhe4,Gly-ol5]enkephalin from μ-opioid receptors suggests that the pre-pro-sequence is cleaved off from the pre-pro-sequence/β-endorphin construct prior to secretion, resulting in bona fide β-endorphin. Transplantation of β-endorphin-secreting cells into brain or spinal cord may provide a gene therapy approach for the treatment of chronic, opioid-sensitive pain states.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1439-6327
    Keywords: Catecholamines ; Insulin ; Growth hormone ; ACTH ; Erythropoietin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To establish whether or not hypoxia influences the training-induced adaptation of hormonal responses to exercise, 21 healthy, untrained subjects [26 (2) years, mean (SE)] were studied in three groups before and after 5 weeks' training (cycle ergometer, 45 min· day−1, 5 days· week−1). Group 1 trained at sea level at 70% maximal oxygen uptake ( $$\dot V$$ O2max), group 2 in a hypobaric chamber at a simulated altitude of 2500 m at 70% of altitude $$\dot V$$ O2max, and group 3 at a simulated altitude of 2500 m at the same absolute work rate as group 1. Arterial blood was sampled before, during and at the end of exhaustive cycling at sea level (85% of pretraining of $$\dot V$$ O2max). $$\dot V$$ O2 increased by 12 (2)% with no significant difference between groups, whereas endurance improved most in group 1 (P 〈 0.05). Training-induced changes in response to exercise of noradrenaline, adrenaline, growth hormone, β-endorphin, glucagon, and insulin were similar in the three groups. Concentrations of erythropoietin and 2,3-diphosphoglycerate at rest did not change over the training period. In conclusion, within 5 weeks of training, no further adaptation of hormonal exercise responses takes place if intensity is increased above 70% $$\dot V$$ O2max. Furthermore, hypoxia per se does not add to the training-induced hormonal responses to exercise.
    Type of Medium: Electronic Resource
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