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- Jerning, C., et al.
(författare)
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Asthma and physical activity - A population based study results from the Swedish GA(2)LEN survey
- 2013
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Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 107:11, s. 1651-1658
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Tidskriftsartikel (refereegranskat)abstract
- Background: Having asthma has in previous reports been related to a lower physical activity level. At the same time the prevalence of asthma among elite athletes is high. The aim of this study was to investigate the association between physical activity level and asthma. Methods: A postal questionnaire was completed by 25,610 individuals in Sweden. Current asthma was defined as having had an asthma attack during the last 12 months or current use of asthma medication. The participants were asked how often and for how many hours a week they were physically active. Results: In the population 1830 subjects (7.1%) had current asthma. There was no significant difference in the proportion of subjects that reported being inactive or slightly physically active between asthmatic and non-asthmatics (57 vs. 58%) while the proportion of subjects that were vigorously physically active (>= 2 times a week and >= 7 h per week) was higher among the subjects with asthma (6.7 vs. 4.8%, p < 0.0001). Being vigorously physically active was independently related to current asthma (OR (95% CI)) 1.40 (1.11-1.77)), wheeze (1.39 (1.17-1.65)), wheeze and breathlessness (1.68 (1.38-2.04)), and wheezing without having a cold (1.39 (1.13-1.71)). The association between being vigorously physically active and wheeze was significantly stronger in women compared to men. Conclusions: There was no difference in the proportion of subjects with a reported low level of physical activity between asthmatics and non-asthmatics. Health care professionals should, however, be aware of the increased prevalence of asthma and asthma-related symptoms in vigorously physically active subjects. (C) 2013 Elsevier Ltd. All rights reserved.
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- Varnäs, K., et al.
(författare)
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Integrated strategy for use of positron emission tomography in nonhuman primates to confirm multitarget occupancy of novel psychotropic drugs : An example with AZD3676
- 2016
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Ingår i: Journal of Pharmacology and Experimental Therapeutics. - : American Society for Pharmacology and Experimental Therapy. - 0022-3565 .- 1521-0103. ; 358:3, s. 464-471
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Tidskriftsartikel (refereegranskat)abstract
- Positron emission tomography (PET) is widely applied in central nervous system (CNS) drug development for assessment of target engagement in vivo. As the majority of PET investigations have addressed drug interaction at a single binding site, findings of multitarget engagement have been less frequently reported and have often been inconsistent with results obtained in vitro. AZD3676 [N,N-dimethyl-7-(4-(2-(pyridin-2-yl)ethyl)piperazin-1-yl) benzofuran-2-carboxamide] is a novel combined serotonin (5- hydroxytryptamine) 5-HT1A and 5-HT1B receptor antagonist that was developed for the treatment of cognitive impairment in Alzheimer's disease. Here, we evaluated the properties of AZD3676 as a CNS drug by combining in vitro and ex vivo radioligand binding techniques, behavioral pharmacology in rodents, and PET imaging in nonhuman primates. Target engagement in the nonhuman primate brain was assessed in PET studies by determination of drug-induced occupancy using receptorselective radioligands. AZD3676 showed preclinical properties consistent with CNS drug potential, including nanomolar receptor affinity and efficacy in rodent models of learning and memory. In PET studies of the monkey brain, AZD3676 inhibited radioligand binding in a dose-dependent manner with similar affinity at both receptors. The equally high affinity at 5-HT1A and 5-HT1B receptors as determined in vivo was not predicted from corresponding estimates obtained in vitro, suggestingmore than 10-fold selectivity for 5-HT1A versus 5-HT1B receptors. These findings support the further integrated use of PET for confirmation of multitarget occupancy of CNS drugs. Importantly, earlier introduction of PET studies in nonhuman primates may reduce future development costs and the requirement for animal experiments in preclinical CNS drug development programs.
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