| 1. |
- Örtqvist, M., et al.
(författare)
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Knee muscle strength-A challenge to measure
- 2014
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Ingår i: European Journal of Physiotherapy. - : Informa UK Limited. - 2167-9169 .- 2167-9177. ; 16:1, s. 33-40
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Tidskriftsartikel (refereegranskat)abstract
- The aims were to assess the reliability of knee extensor and flexor muscle strength measurements using the Strength Measuring Chair (SMC) in children and adults, and to assess agreement between the SMC and an isokinetic dynamometer (ID). 20 healthy children (10/10 boys/girls, 5-13 years) and 23 adults (10/13 men/women, 23-60 years) were included. Muscle strength tests were performed in the SMC and in the ID. The intra-subject reliability was shown to be excellent in both instruments (ICC 0.93-0.99) and an excellent test-retest reliability of measurements in the SMC was found (ICC 0.87-0.93). Agreement between instruments was evaluated with ICC, paired t-test and Bland-Altman 95% limits of agreement plots. In both adults' and children's groups, disagreements were found between the two instruments, with more in the children's group. The SMC, which has previously shown to be valid and reliable for measuring plantarflexor muscle strength, reliably measured knee muscle strength in healthy children and adults. However, the large disagreement found between the instruments, especially in the children's group, warrants care in standardizing measuring positions for different body size and warrants caution in comparing one's muscle strength measured using different assessment methods.
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| 2. |
- Örtqvist, Pernilla, et al.
(författare)
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Structure-activity relationships of HCV NS3 protease inhibitors evaluated on the drug-resistant variants A156T and D168V
- 2010
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Ingår i: Antiviral Therapy. - 1359-6535 .- 2040-2058. ; 15:6, s. 841-852
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: HCV infections are a serious threat to public health. An important drug target is the NS3 protease, for which several inhibitors are in clinical trials. Because of the high mutation rate of the virus, resistance against any HCV-specific drug is likely to become a substantial problem. Structure-activity data for the major resistant variants are therefore needed to guide future designs of protease inhibitors. METHODS: The inhibitory potency of tripeptide NS3 protease inhibitors, with either a P2 proline or phenylglycine, in combination with different P3 and P1-P1' groups, was assessed in enzyme activity assays using the full-length NS3 protein with known resistance-conferring substitutions A156T or D168V. The results obtained from these variants were compared with the inhibition of the wild-type enzyme. Molecular modelling was used to rationalize the biochemical results. RESULTS: Inhibitors combining the P2 proline and P1 (1R,2S)-1-amino-2-vinylcyclopropyl-carboxylic acid (vinylACCA) lost much of their potency on the resistant variants. Exchange of the P2 proline for phenylglycine yielded inhibitors that were equipotent on the wild-type and on the A156T and D168V variants. The same result was obtained from the combination of either the P2 residue with a norvaline or an aromatic scaffold in the P1 position. CONCLUSIONS: The combination of a substituted P2 proline and P1 vinylACCA appears to be the main problem behind the observed resistance. Molecular modelling suggests an enforced change in binding conformation for the P2 proline-based inhibitors, whereas the phenylglycine-based inhibitors retained their wild-type binding conformation in the substituted forms of the enzyme.
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