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I Sayers J Hawley CE Stewart CK Billington A Henry JR Leighton-Davies SJ Charlton IP Hall 《British journal of pharmacology》2009,158(1):277-286
Background and purpose:
Indacaterol is a novel β2-adrenoceptor agonist in development for the treatment of chronic obstructive pulmonary disease. The aim of this study was to investigate the comparative pharmacology of indacaterol in recombinant cells expressing the common polymorphic variants of the human β2-adrenoceptor and in human primary airway smooth muscle (ASM) cells.Experimental approach:
Chinese hamster ovarian-K1 cell lines expressing high and low levels of the common human β2-adrenoceptor variants were generated [Gly16-Glu27-Val34-Thr164(GEVT), RQVT, GQVT] and also the rare GQVI variant. Human primary ASM cells were isolated from explants of trachealis muscle. Adenosine-3′,5′-cyclic-monophosphate production was used as an outcome measure.Key results:
In both the low- and high-expression recombinant GEVT ‘wild type’ cell lines indacaterol is a high-efficacy agonist. Salmeterol and formoterol were identified as low- and high-efficacy agonists, respectively, and showed similar potencies to indacaterol irrespective of the β2-adrenoceptor genotype. The I164 variant cell line was associated with a reduced capacity to generate adenosine-3′,5′-cyclic-monophosphate in response to β2-adrenoceptor agonist. In the human primary ASM cells indacaterol gave a maximal response intermediate between that of salmeterol and formoterol.Conclusions and implications:
These data demonstrate that indacaterol is a high-efficacy agonist in recombinant cell systems but acts with lower efficacy in human primary ASM cells. No marked genotype-dependent effects were observed for common variants; however, changes in I164 receptor activity were identified, which were dependent on the level of expression of β2-adrenoceptors. 相似文献93.
SB Cho SJ Lee S Cho SH Oh WS Chung JM Kang YK Kim DH Kim 《Journal of the European Academy of Dermatology and Venereology》2010,24(8):921-925
Background Non‐ablative 1550‐nm erbium‐doped fractional photothermolysis systems (FPS) and 10 600‐nm carbon dioxide fractional laser systems (CO2 FS) have been effectively used to treat scars. Objective We compared the efficacy and safety of single‐session treatments of FPS and CO2 FS for acne scars through a randomized, split‐face, evaluator‐blinded study. Methods Eight patients with acne scars were enrolled in this study. Half of each subject’s face was treated with FPS and the other half was treated with CO2 FS. We used a quartile grading scale for evaluations. Results At 3 months after the treatment, the mean grade of improvement based on clinical assessment was 2.0 ± 0.5 for FPS and 2.5 ± 0.8 for CO2 FS. On each side treated by FPS and CO2 FS, the mean duration of post‐therapy crusting and scaling was 2.3 and 7.4 days respectively and that of post‐therapy erythema was 7.5 and 11.5 days respectively. The mean VAS pain score was 3.9 ± 2.0 with the FPS and 7.0 ± 2.0 with the CO2 FS. Conclusion We demonstrated the efficacy and safety of single‐session acne scar treatment using FPS and CO2 FS in East Asian patients. We believe that our study could be used as an essential reference when choosing laser modalities for scar treatment. 相似文献
94.
Scales for the measurement of attitudes toward blood donation 总被引:1,自引:0,他引:1
Attitudes toward blood donation are frequently assumed to vary along a single dimension from unfavorable to favorable. In contrast, theories of attitude structure specify three distinct attitude components: affect, cognition, and behavior. This article describes the development of three new scales for the measurement of affective, cognitive, and behavioral components of attitudes toward blood donation. The scales were developed using the method of equal-appearing intervals and were administered to both donors of blood and nondonors. Correlations among the scales were relatively small and supported the three-component distinction. Affect was more strongly correlated with the number of prior donations than was cognition, which suggested an important role for emotional factors in blood donation. Scores on all three scales showed the attitudes of blood donors to be more favorable than those of nondonors. 相似文献
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SJ Mundell A-L Matharu S Nisar TM Palmer JL Benovic E Kelly 《British journal of pharmacology》2010,159(3):518-533
Background and purpose:
We have investigated the effect of deletions of a postsynaptic density, disc large and zo-1 protein (PDZ) motif at the end of the COOH-terminus of the rat A2B adenosine receptor on intracellular trafficking following long-term exposure to the agonist 5′-(N-ethylcarboxamido)-adenosine.Experimental approach:
The trafficking of the wild type A2B adenosine receptor and deletion mutants expressed in Chinese hamster ovary cells was studied using an enzyme-linked immunosorbent assay in combination with immunofluorescence microscopy.Key results:
The wild type A2B adenosine receptor and deletion mutants were all extensively internalized following prolonged treatment with NECA. The intracellular compartment through which the Gln325-stop receptor mutant, which lacks the Type II PDZ motif found in the wild type receptor initially trafficked was not the same as the wild type receptor. Expression of dominant negative mutants of arrestin-2, dynamin or Eps-15 inhibited internalization of wild type and Leu330-stop receptors, whereas only dominant negative mutant dynamin inhibited agonist-induced internalization of Gln325-stop, Ser326-stop and Phe328-stop receptors. Following internalization, the wild type A2B adenosine receptor recycled rapidly to the cell surface, whereas the Gln325-stop receptor did not recycle.Conclusions and implications:
Deletion of the COOH-terminus of the A2B adenosine receptor beyond Leu330 switches internalization from an arrestin- and clathrin-dependent pathway to one that is dynamin dependent but arrestin and clathrin independent. The presence of a Type II PDZ motif appears to be essential for arrestin- and clathrin-dependent internalization, as well as recycling of the A2B adenosine receptor following prolonged agonist addition. 相似文献100.
Summary The purpose of this study was to evaluate the occurrence of superficial flaws after machining and to identify fracture initiation and propagation in three‐unit heat‐treated machined fixed partial dentures (FPDs) substructures made of hot isostatic pressed (HIPed) yttria‐stabilized tetragonal zirconia polycrystal (Y‐TZP) after loaded to fracture. Four three‐unit HIPed Y‐TZP‐based FPDs substructures were examined. To evaluate the occurrence of superficial flaws after machining, the surfaces were studied utilizing a fluorescent penetrant method. After static loading to fracture, characteristic fracture features on both mating halves of the fractured specimens were studied using a stereomicroscope and a scanning electron microscope. Grinding grooves were clearly visible on the surfaces of the machined FPDs substructures, but no other flaws could be seen with the fluorescent penetrant method. After loading to fracture, the characteristic fracture features of arrest lines, compression curl, fracture mirror, fracture origin, hackle and twist hackle were detected. These findings indicated that the decisive fracture was initiated at the gingival embrasure of the pontic in association with a grinding groove. Thus, in three‐unit heat‐treated machined HIPed Y‐TZP FPDs substructures, with the shape studied in this study, the gingival embrasure of the pontic seems to be a weak area providing a location for tensile stresses when they are occlusally loaded. In this area, fracture initiation may be located to a grinding groove. 相似文献