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- Gerdin, Linda, et al.
(författare)
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Acute psychological stress increases paracellular permeability and modulates immune activity in rectal mucosa of healthy volunteers
- 2023
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Ingår i: United European Gastroenterology journal. - : John Wiley & Sons Ltd. - 2050-6406 .- 2050-6414. ; 11:1, s. 31-41
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Tidskriftsartikel (refereegranskat)abstract
- Background Psychological stress and increased permeability are implicated as contributing factors in the initiation and worsening of gastrointestinal diseases. A link between stress and intestinal permeability has been shown in animal models as well as in human small intestine, but stress effects on the human colorectal mucosal barrier has not been reported. Objective To investigate the potential effects of acute psychological stress on colorectal mucosal barrier function and to explore stress-induced molecular events in the rectal mucosa under healthy conditions. Methods Endoscopic biopsies were taken from the rectosigmoid region of healthy volunteers, who had been subjected to dichotomous listening stress and after a control session, respectively. Paracellular and transcellular permeability were assessed in modified Ussing chambers. RNA expression (microarray technology confirmed by quantitative real-time polymerase chain reaction) and biological pathway analysis were used to investigate the local mucosal response to acute stress. Results Dichotomous listening stress induced a subjective and objective stress response, and significantly increased paracellular but not transcellular permeability. We also identified a stress-induced reduction in RNA expression of genes related to immune cell activation and maturation (CR2, CD20, TCLA1, BANK1, CD22, FDCSP), signaling molecules of homing of immune cells to the gut (chemokines: CCL21, CXCL13, and CCL19, and receptors: CCR7, CXCR5), and innate immunity (DUOX2). Eight of the 10 top down-regulated genes are directly involved in B cell activation, signaling and migration. The systemic stress response correlated positively with paracellular permeability and negatively with DUOX2 expression. Conclusion Dichotomous listening stress increases paracellular permeability and modulates immune cell activity in the rectal mucosa. Further studies are warranted to identify the primary mechanisms of stress-mediated reduction of mucosal defensive activity and barrier dysfunction, and their potential implications for gastrointestinal disorders.
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| 2. |
- Gerdin, Linda, et al.
(författare)
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The Swedish Crohn Trial: A Prematurely Terminated Randomized Controlled Trial of Thiopurines or Open Surgery for Primary Treatment of Ileocaecal Crohns Disease
- 2016
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Ingår i: Journal of Crohn's & Colitis. - : OXFORD UNIV PRESS. - 1873-9946 .- 1876-4479. ; 10:1, s. 50-54
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: The importance of efficient and safe treatment of Crohns disease is highlighted by its chronicity. Both medical and surgical treatments have shown good results in the symptomatic control of limited ileocaecal Crohns disease. The aim of this study was to compare medical treatment with surgical treatment of ileocaecal Crohns disease. Methods: Thirty-six patients from seven hospitals with primary ileocaecal Crohns disease were randomized to either medical or surgical treatment. The medical treatment was induction of remission with budesonide and thereafter maintenance treatment with azathioprine. The surgical treatment was open ileocaecal resection. Crohns disease activity index over time, expressed as area under the curve at 1, 3 and 5 years, was the primary endpoint. Subjective health measured with the 36-item Short Form Survey Instrument (SF36) and a visual analogue scale (VAS) were secondary endpoints. Results: There were no differences between the treatment groups in Crohns disease activity index over time. General health, measured as SF36 score, was higher in patients receiving surgical treatment than in those receiving medical treatment at 1 year, but there was no corresponding difference in VAS. Due to the slow inclusion rate and changes in clinical practice, the study was t = erminated prematurely. Conclusion: The study ended up being underpowered and should be interpreted with caution, but there was no clinically significant difference between the two treatment arms. Further studies are needed to address this important clinical question.
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| 3. |
- Linton, Gabriel, 1982-
(författare)
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Entrepreneurial orientation : reflections from a contingency perspective
- 2016
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Entrepreneurship has been argued to be a key driver of the economy by creating jobs, turning inventions to innovations, and also improving the overall standard of life. A firm’s entrepreneurial orientation (EO) indicates the degree to which a firm is entrepreneurial. However, there are several different approaches to conceptualizing the EO concept and its sub-dimensions, frequently described as innovativeness, risk taking, and proactiveness. The role of the sub-dimensions is not quite clear in the EO literature. Furthermore, many studies claim that firms can increase their performance simply by increasing their EO, while this thesis draws upon contingency theory to argue that EO needs to be aligned with—‘fit’ the internal and external context, if the firm is to perform well. Thus, this thesis aims to advance the conceptualization of EO by problematizing the core construct and also discussing how EO can fit with context. The thesis consists of four papers in which the EO concept is elaborated on and contingency theory is applied to construct conceptual models of the interaction between EO and different contexts, which are also empirically investigated. Furthermore, the sub-dimensions of EO are discussed in terms of their meanings and measurement to point out their individual impact on the EO.The overall findings indicate that EO is not as simple a concept as often portrayed in the EO literature. Rather, EO is more complex in the ways that it can fit with internal and external context and, on these bases, it is suggested that ideal types of EO and context is a way forward for research in the area. Additionally, it is argued that EO as a theoretical construct may not only be conceptualized as an overall entrepreneurial attribute (which is common in the extant literature), but also as a complex and granular attribute.
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