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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
1995-10-25
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pubmed:abstractText |
The peptide hormone calcitonin (CT) is a potent drug for the therapy of different bone diseases. Salmon CT (sCT) is reported to be more active than human CT (hCT). Human CT, but not sCT, has a strong tendency to aggregate and fibrillate in aqueous solutions. Recent investigations of the fibrillation mechanisms contributed to the development of hCT solutions in which fibrillation is inhibited. Taking into consideration these new findings, we tested the relative activities of hCT handled so as to avoid aggregation/fibrillation, sCT handled in exactly the same way, and hCT handled carefully but without regard to possible fibrillation (denoted R-hCT). The effect of the CTs on bone resorption by isolated osteoclasts was measured. This assay measures the activity of interest (bone resorption) by the cell (the osteoclast) at which therapy is directed. The concentration that inhibits 50% of resorption (EC50) for hCT is 10(-5)-10(-4) pg/mL, compared with 10(-2)-1 pg/mL for R-hCT and 10(-3)-10(-1) pg/mL for sCT. The results show that when aggregation and fibrillation are avoided, hCT at the EC50 is 2-4 orders of magnitude more active than R-hCT. Thus, earlier reports of lower potency of hCT compared with sCT may have been based on inadvertent use of partially aggregated/fibrillated samples of hCT. This finding may have implications for the dose and dosage forms advised for human therapy.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Analgesics,
http://linkedlifedata.com/resource/pubmed/chemical/Calcitonin,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Solutions,
http://linkedlifedata.com/resource/pubmed/chemical/salmon calcitonin
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0022-3549
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
84
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
717-9
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:7562410-Analgesics,
pubmed-meshheading:7562410-Animals,
pubmed-meshheading:7562410-Bone Resorption,
pubmed-meshheading:7562410-Bone and Bones,
pubmed-meshheading:7562410-Calcitonin,
pubmed-meshheading:7562410-Culture Techniques,
pubmed-meshheading:7562410-Humans,
pubmed-meshheading:7562410-Osteoclasts,
pubmed-meshheading:7562410-Rats,
pubmed-meshheading:7562410-Rats, Sprague-Dawley,
pubmed-meshheading:7562410-Recombinant Proteins,
pubmed-meshheading:7562410-Solutions
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pubmed:year |
1995
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pubmed:articleTitle |
Enhanced potency of human calcitonin when fibrillation is avoided.
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pubmed:affiliation |
William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London, U.K.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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