1.
Lind, Simon, et al.
(författare)
Functional selective FPR1 signaling in favor of an activation of the neutrophil superoxide generating NOX2 complex
2020
Ingår i: Journal of Leukocyte Biology. - : Oxford University Press (OUP). - 0741-5400 .- 1938-3673. ; 109:6, s. 1105-1120
Tidskriftsartikel (refereegranskat) abstract
The formyl peptide receptors FPR1 and FPR2 are abundantly expressed by neutrophils, in which they regulate proinflammatory tissue recruitment of inflammatory cells, the production of reactive oxygen species (ROS), and resolution of inflammatory reactions. The unique dual functionality of the FPRs makes them attractive targets to develop FPR-based therapeutics as novel anti-inflammatory treatments. The small compound RE-04-001 has earlier been identified as an inducer of ROS in differentiated HL60 cells but the precise target and the mechanism of action of the compound was has until now not been elucidated. In this study, we reveal that RE-04-001 specifically targets and activates FPR1, and the concentrations needed to activate the neutrophil NADPH-oxidase was very low (EC50 ∼1 nM). RE-04-001 was also found to be a neutrophil chemoattractant, but when compared to the prototype FPR1 agonist N-formyl-Met-Leu-Phe (fMLF), the concentrations required were comparably high, suggesting that signaling downstream of the RE-04-001-activated-FPR1 is functionally selective. In addition, the RE-04-001-induced response was strongly biased toward the PLC-PIP2 -Ca2+ pathway and ERK1/2 activation but away from β-arrestin recruitment. Compared to the peptide agonist fMLF, RE-04-001 is more resistant to inactivation by the MPO-H2 O2 -halide system. In summary, this study describes RE-04-001 as a novel small molecule agonist specific for FPR1, which displays a biased signaling profile that leads to a functional selective activating of human neutrophils. RE-04-001 is, therefore, a useful tool, not only for further mechanistic studies of the regulatory role of FPR1 in inflammation in vitro and in vivo, but also for developing FPR1-specific drug therapeutics.
2.
Axelsson, Malin, 1964-, et al.
(författare)
Personality, adherence, asthma control and health-related quality of life in young adult asthmatics
2009
Ingår i: Respiratory Medicine. - : Elsevier. - 0954-6111 .- 1532-3064. ; 103:7, s. 1033-1040
Tidskriftsartikel (refereegranskat) abstract
BackgroundStriving for improved adherence and asthma control is of vital concern in today's asthma management. Several influential factors have been identified, but the importance of personality traits has been insufficiently explored. The aim was first to determine whether personality traits in young adult asthmatics are related to asthma control and health-related quality of life (HRQL), and second to examine the influences of personality traits on adherence to regular asthma medication treatment.MethodsYoung adult asthmatics, 22 years of age (n = 268) completed questionnaires. Statistical analyses were performed.ResultsThe personality traits Negative Affectivity and Impulsivity correlated negatively with asthma control, whereas in women Hedonic Capacity correlated positively with asthma control. Negative Affectivity, Impulsivity, Hedonic Capacity, Alexithymia and asthma control predicted the mental dimension of HRQL. Asthma control and physical activity predicted the physical dimension of HRQL. Among respondents with regular asthma medication (n = 109), Impulsivity correlated negatively with adherence. In men, Antagonism and Alexithymia were associated with low adherence. Additionally, Alexithymia, Hedonic Capacity and Negative Affectivity showed non-linear relationships with adherence, meaning that initially increased scores on these personality traits scales were associated with increased adherence but higher scores did not increase adherence. Respondents who were prescribed a single inhaler combining ICS and LABA reported higher adherence than those with monotherapies.ConclusionThese data suggest that personality can influence how asthma patients adhere to asthma medication treatment, and report their control and HRQL. Tools determining personality traits may be useful in the future in individualizing management of asthma patients.
3.
Emilsson, Maria, 1966-, et al.
(författare)
The Influence of personality traits and beliefs about medicines on adherence to asthma treatment
2011
Ingår i: Primary Care Respiratory Journal. - : Strategic Medical Pub. - 1471-4418 .- 1475-1534. ; 20:2, s. 141-147
Forskningsöversikt (refereegranskat) abstract
Aim:To explore the influence of personality traits and beliefs about medicines on adherence to treatment with asthma medication.Methods:Respondents were 35 asthmatic adults prescribed controller medication. They answered questionnaires about medication adherence, personality traits, and beliefs about medicines.Results:In gender comparisons, the personality traits “Neuroticism” in men and “adherence to medication” were associated with lower adherent behaviour. Associations between personality traits and beliefs in the necessity of medication for controlling the illness were identified. Beliefs about the necessity of medication were positively associated with adherent behaviour in women. In the total sample, a positive “necessity-concern” differential predicted adherent behaviour.Conclusion:The results imply that personality and beliefs about medicines may influence how well adults with asthma adhere to treatment with asthma medication.
4.
Gellerstedt, Martin, 1966-, et al.
(författare)
Methodological issues in the diagnostic work-up of food allergy : a real challenge.
2007
Ingår i: Journal of investigational allergology & clinical immunology. - Barcelona : J.R. Prous, S.A. - 1018-9068 .- 1698-0808. ; 17:6, s. 350-356
Tidskriftsartikel (refereegranskat) abstract
The standard of reporting in diagnostic studies has generally been low. Fortunately, this issue has begun to be addressed in recent years through the discussion of important methodological issues in educational series, textbooks, and checklists. Double-blind, placebo-controlled, oral food challenges (DBPCFC) are considered to be the gold standard for diagnosis of food allergy. However, there is no consensus regarding how to interpret the outcome and how to define positive and negative provocations in DBPCFC. Furthermore, since most theories on the diagnosis of food allergy rely on the assumption that the DBPCFC has a high accuracy, this accuracy must be formally statistically evaluated. In this review, we discuss essential methodological issues for diagnostic accuracy studies in general and for oral food challenges in particular and discuss the importance of methodological issues as a guide for forthcoming studies of diagnostic procedures.
