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Theodorsson, Elvar
Publications (10 of 180) Show all publications
Lund, M. L., Egerod, K. L., Engelstoft, M. S., Dmytriyeva, O., Theodorsson, E., Patel, B. A. & Schwartz, T. W. (2018). Enterochromaffin 5-HT cells: A major target for GLP-1 and gut microbial metabolites. MOLECULAR METABOLISM, 11, 70-83
Open this publication in new window or tab >>Enterochromaffin 5-HT cells: A major target for GLP-1 and gut microbial metabolites
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2018 (English)In: MOLECULAR METABOLISM, ISSN 2212-8778, Vol. 11, p. 70-83Article in journal (Refereed) Published
Abstract [en]

Objectives

5-HT storing enterochromaffin (EC) cells are believed to respond to nutrient and gut microbial components, and 5-HT receptor-expressing afferent vagal neurons have been described to be the major sensors of nutrients in the GI-tract. However, the molecular mechanism through which EC cells sense nutrients and gut microbiota is still unclear.

Methods and results

TPH1, the 5-HT generating enzyme, and chromogranin A, an acidic protein responsible for secretory granule storage of 5-HT, were highly enriched in FACS-purified EC cells from both small intestine and colon using a 5-HT antibody-based method. Surprisingly, EC cells from the small intestine did not express GPCRsensors for lipid and protein metabolites, such as FFAR1, GPR119, GPBAR1(TGR5), CaSR, and GPR142, in contrast to the neighboring GLP-1 storing enteroendocrine cell. However, the GLP-1 receptor was particularly highly expressed and enriched in EC cells as judged both by qPCR and by immunohistochemistryusing a receptor antibody. GLP-1 receptor agonists robustly stimulated 5-HT secretion from intestinal preparations using both HPLC and a specific amperometricmethod. Colonic EC cells expressed many different types of known and potential GPCR sensors of microbial metabolites including three receptors for SCFAs, i.e. FFAR2, OLF78, and OLF558 and receptors for aromatic acids, GPR35; secondary bile acids GPBAR1; and acyl-amides and lactate, GPR132.

Conclusion

Nutrient metabolites apparently do not stimulate EC cells of the small intestine directly but through a paracrine mechanism involving GLP-1 secreted from neighboring enteroendocrine cells. In contrast, colonic EC cells are able to sense a multitude of different metabolites generated by the gut microbiota as well as gut hormones, including GLP-1.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Metabolite GPCR; Nutrient sensing; Gut microbiota; Gut hormone; Enteroendocrine; Afferent vagal nerves
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-150300 (URN)10.1016/j.molmet.2018.03.004 (DOI)000439548700006 ()29576437 (PubMedID)2-s2.0-85044298641 (Scopus ID)
Note

Funding Agencies|Novo Nordisk Foundation [NNF10CC1016515, NNF15CC0018346, NNF15OC0016798, NNF14OC0016798]; Danish Council for Independent Research [7016-00389A]

Available from: 2018-08-16 Created: 2018-08-16 Last updated: 2018-09-07Bibliographically approved
Sinkvist, D., Theodorsson, A., Ledin, T. & Theodorsson, E. (2017). Five Year Data and Results of Continuous Quality Improvement Using SKURT. Educational Research Applications, 2017(05), Article ID ERCA-125.
Open this publication in new window or tab >>Five Year Data and Results of Continuous Quality Improvement Using SKURT
2017 (English)In: Educational Research Applications, E-ISSN 2575-7032, Vol. 2017, no 05, article id ERCA-125Article in journal (Refereed) Published
Abstract [en]

Student rating of teaching isessentialfor attaining and maintaining higheducational quality.A quality improvement system, SKURT,based on digital online weekly combined quantitative, ten-graded scale, and qualitative, open-ended free text, group feedback from medical students was developed. Students rated all educational, non-clerkship, items throughout the entire medical program, spanning eleven terms. The results were semi-publicly available for students and faculty at a Swedish university. This study describes datafrom five-year use of the system,focusing on how the use of SKURT influenced educational items found to be in the most substantial need for improvements.

Statistically but hardly practically significant improvement in average feedback grade was found during the observation period (average 7.07 in 2009 to 7.24 in 2013 (p<0.001)).The medical program was already in 2007recognized ascenter of excellent quality in higher education. When analyzing the 18 lectures with lowest outcome in the spring 2009 compared to the fall 2013, five were discontinued. The remaining 13 lectures improved significantly (p<0.001) 116% from 2.94 (SD 0.92) to 6.34 (SD 2.58). 

A weekly group feedback system employing the principles used in SKURTis useful forimproving the quality of medical education particularlyby improvingthe items with the lowest ratings.

Place, publisher, year, edition, pages
IL, USA: Gavin Publishers, 2017
Keywords
Medical Education; Online Evaluation; Problem-based Learning; Quality Improvement; Rating of Teachers; Student Evaluation
National Category
Other Health Sciences
Identifiers
urn:nbn:se:liu:diva-145230 (URN)10.29011/2575-7032/100025 (DOI)
Available from: 2018-02-19 Created: 2018-02-19 Last updated: 2018-02-27Bibliographically approved
Sörbo, A., Eiving, I., Theodorsson, E. & Rydenhag, B. (2017). Hair Cortisol as a Biomarker of Stress before and after Subarachnoid Hemorrhage: A Case Report. Remedy Open Access, 2, Article ID 1062.
Open this publication in new window or tab >>Hair Cortisol as a Biomarker of Stress before and after Subarachnoid Hemorrhage: A Case Report
2017 (English)In: Remedy Open Access, E-ISSN 2573-6078, Vol. 2, article id 1062Article in journal (Refereed) Published
Abstract [en]

The aim was to study stress in the acute and post-acute phase in patients with severe traumaticbrain injury (TBI) or non-traumatic subarachnoid hemorrhage (SAH) who were treated at theneurointensive care unit (NICU). Hair cortisol is a biomarker of stress via alterations in hypothalamuspituitary-adrenal axis activity, where cortisol from plasma is continuously incorporated intogrowing hairs at their roots. As hair grows at an average of 1 cm/month, concentrations of haircortisol can also be used to measure stress levels retrospectively.

Hair samples were collected at an interval of one month until three months, with the first cut atadmission to the NICU. The patients (or their relatives, if the patient was unable to communicate)were interviewed about psychological or physical stressors during the previous months.

We present a 28-year-old woman suffering from a subarachnoid hemorrhage (SAH), studied withrepeated haircuts. She experienced the sudden onset of a severe headache. The general practitionersdiagnosed it as migraine or wry neck. Three weeks later, she experienced another attack ofsevere headache. A CT scan showed an SAH. Six months after the SAH, the patient developedhydrocephalus and was successfully treated with a VP shunt. In this case, hair cortisol was elevatedduring the pre-hospital month (probably because of pain and stress due to a sentinel or “warning”leak), during the intensive care period and until two months after the SAH. It then normalized, butit was elevated again at the time at which the patient developed hydrocephalus. At the nine-monthhaircut, her hair cortisol had again normalized.

This case indicates that hair cortisol measurement is a promising method for studying stress,retrospectively and during recovery, in patients suffering from SAH.

Place, publisher, year, edition, pages
Remedy Publications, 2017
Keywords
Traumatic brain injury; Subarachnoid hemorrhage; Hair cortisol
National Category
Neurology Clinical Laboratory Medicine
Identifiers
urn:nbn:se:liu:diva-145275 (URN)
Available from: 2018-02-20 Created: 2018-02-20 Last updated: 2018-02-27Bibliographically approved
Sinkvist, D., Theodorsson, A., Ledin, T. & Theodorsson, E. (2017). SKURT: Quality Improvement System with Comprehensive Weekly Digital Student Group Feedback. Educational Research Applications, 2017(5), Article ID RCA-124.
Open this publication in new window or tab >>SKURT: Quality Improvement System with Comprehensive Weekly Digital Student Group Feedback
2017 (English)In: Educational Research Applications, E-ISSN 2575-7032, Vol. 2017, no 5, article id RCA-124Article in journal (Refereed) Published
Abstract [en]

Students’ role in evaluation and rating of teachers and education has been extensively researched for nearly a century. Applied worldwide, students’ ratings account for the majority of the available data.We created a new quality improvement system, SKURT, using digital online weekly combined quantitative, ten-graded scale, and qualitative, open-ended free text, group feedback from medical students. Students rated all educational, non-clerkship, items throughout the entire medical program, spanning eleven terms. The rating process is since 2008 an integral part of a medical program at a Swedish university. The results are, after a screening process, semi-publicly available on-demand, for students and faculty, creating a feedback loop enabling continuous improvement of quality.A thorough literature search of students rating of teaching found no other corresponding weekly group rating system spanning all educational items. Quality improvement systems based on similar principles as SKURT can uncover problem areas that are difficult to find using other rating systems and has the potential to circumvent several biases, risks and shortcomings of traditional rating systems in current use.

Place, publisher, year, edition, pages
Gavin Publishers, 2017
Keywords
Medical Education; Online Evaluation; Problem-Based Learning; Quality Improvement; Rating of Teachers; Student Evaluation
National Category
Other Health Sciences
Identifiers
urn:nbn:se:liu:diva-145282 (URN)
Available from: 2018-02-20 Created: 2018-02-20 Last updated: 2018-03-08Bibliographically approved
Theodorsson, E. (2017). Validation and verification in clinical chemistry. Klinisk biokemi i Norden, 1(29), 8-16
Open this publication in new window or tab >>Validation and verification in clinical chemistry
2017 (English)In: Klinisk biokemi i Norden, ISSN 1101-2013, Vol. 1, no 29, p. 8-16Article, review/survey (Other academic) Published
Abstract [en]

Measurement systems used inclinical chemistry are usuallymanufactured by internationalcompanies working according toin vitro directive (IVD) – regulations.This means that medicallaboratories do not need to validatecommercially available measurement systems,but are obliged to verify that their properties foundduring the producers validation can be reproducedin the users laboratories. Developments in healthcareand accreditation standards including ISO 15189focus increasingly on customer needs which maycall for the validation of entire conglomerates oflaboratories and measurement systems catering forthe needs for the same patient population. Such validationpractices are, however, still in their infancy.The purpose of the present paper is to offer practicaldetails on the common practice of verificationof single measurement systems and add perspectiveson the validation of conglomerates of laboratoriesand measurement systems. Method validation acrossconglomerates of laboratories using verified commerciallyavailable measurement systems can only beperformed by the laboratories – users themselves intheir own circumstances. The use of patient samplesin split- sample techniques is especially valuable inthis contexts in order to avoid compatibility issues.

Place, publisher, year, edition, pages
Nordisk Forening for Klinisk Kemi, 2017
National Category
Clinical Laboratory Medicine
Identifiers
urn:nbn:se:liu:diva-134921 (URN)
Available from: 2017-03-02 Created: 2017-03-02 Last updated: 2017-03-02
Ivars, K., Nelson Follin, N., Theodorsson, A., Theodorsson, E., Ström, J. & Mörelius, E. (2016). Correction: Development of Salivary Cortisol Circadian Rhythm and Reference Intervals in Full-Term Infants. PLoS ONE, 11(3), Article ID e0151888.
Open this publication in new window or tab >>Correction: Development of Salivary Cortisol Circadian Rhythm and Reference Intervals in Full-Term Infants
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2016 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 3, article id e0151888Article in journal, Editorial material (Other academic) Published
Abstract [en]

BACKGROUND:

Cortisol concentrations in plasma display a circadian rhythm in adults and children older than one year. Earlier studies report divergent results regarding when cortisol circadian rhythm is established. The present study aims to investigate at what age infants develop a circadian rhythm, as well as the possible influences of behavioral regularity and daily life trauma on when the rhythm is established. Furthermore, we determine age-related reference intervals for cortisol concentrations in saliva during the first year of life.

METHODS:

130 healthy full-term infants were included in a prospective, longitudinal study with saliva sampling on two consecutive days, in the morning (07:30-09:30), noon (10:00-12:00) and evening (19:30-21:30), each month from birth until the infant was twelve months old. Information about development of behavioral regularity and potential exposure to trauma was obtained from the parents through the Baby Behavior Questionnaire and the Life Incidence of Traumatic Events checklist.

RESULTS:

A significant group-level circadian rhythm of salivary cortisol secretion was established at one month, and remained throughout the first year of life, although there was considerable individual variability. No correlation was found between development of cortisol circadian rhythm and the results from either the Baby Behavior Questionnaire or the Life Incidence of Traumatic Events checklist. The study presents salivary cortisol reference intervals for infants during the first twelve months of life.

CONCLUSIONS:

Cortisol circadian rhythm in infants is already established by one month of age, earlier than previous studies have shown. The current study also provides first year age-related reference intervals for salivary cortisol levels in healthy, full-term infants.

Place, publisher, year, edition, pages
Public Library of Science, 2016
National Category
Pediatrics Psychology (excluding Applied Psychology)
Identifiers
urn:nbn:se:liu:diva-127497 (URN)10.1371/journal.pone.0151888 (DOI)26086734 (PubMedID)
Available from: 2016-04-28 Created: 2016-04-28 Last updated: 2017-11-30Bibliographically approved
Ingberg, E., Theodorsson, E., Theodorsson, A. & Ström, J. (2016). Effects of high and low 17 beta-estradiol doses on focal cerebral ischemia in rats. Scientific Reports, 6(20228)
Open this publication in new window or tab >>Effects of high and low 17 beta-estradiol doses on focal cerebral ischemia in rats
2016 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, no 20228Article in journal (Refereed) Published
Abstract [en]

The majority of the numerous animal studies of the effects of estrogens on cerebral ischemia have reported neuroprotective results, but a few have shown increased damage. Differences in hormone administration methods, resulting in highly different 17 beta-estradiol levels, may explain the discrepancies in previously reported effects. The objective of the present study was to test the hypothesis that it is the delivered dose per se, and not the route and method of administration, that determines the effect, and that high doses are damaging while lower doses are protective. One hundred and twenty ovariectomized female Wistar rats (n = 40 per group) were randomized into three groups, subcutaneously administered different doses of 17 beta-estradiol and subjected to transient middle cerebral artery occlusion. The modified sticky tape test was performed after 24 h and the rats were subsequently sacrificed for infarct size measurements. In contrast to our hypothesis, a significant negative correlation between 17 beta-estradiol dose and infarct size was found (p = 0.018). Thus, no support was found for the hypothesis that 17 beta-estradiol can be both neuroprotective and neurotoxic merely depending on dose. In fact, on the contrary, the findings indicate that the higher the dose of 17 beta-estradiol, the smaller the infarct.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2016
National Category
Other Biological Topics
Identifiers
urn:nbn:se:liu:diva-125674 (URN)10.1038/srep20228 (DOI)000369323500001 ()26839007 (PubMedID)
Note

Funding Agencies|County Council of Ostergotland, Sweden

Available from: 2016-03-02 Created: 2016-02-29 Last updated: 2017-05-03
Ingberg, E., Theodorsson, E., Theodorsson, A. & Ström, J. O. (2016). Effects of high and low 17β-estradiol doses on focal cerebral ischemia in rats.
Open this publication in new window or tab >>Effects of high and low 17β-estradiol doses on focal cerebral ischemia in rats
2016 (English)Manuscript (preprint) (Other academic)
Abstract [en]

The majority of the numerous animal studies of the effects of estrogens on cerebral ischemia have reported neuroprotective results, but a few have shown increased damage. Differences in hormone administration methods, resulting in highly different 17β-estradiol levels, may explain the discrepancies in previously reported effects. The objective of the present study was to test the hypothesis that it is the delivered dose per se, and not the route and method of administration, that determines the effect, and that high doses are damaging while lower doses are protective. One hundred and twenty ovariectomized female Wistar rats (n=40 per group) were randomized into three groups, subcutaneously administered different doses of 17β-estradiol and subjected to transient middle cerebral artery occlusion. The modifi ed sticky tape test was performed after 24 h and the rats were subsequently sacrifi ced for infarct size measurements. In contrast to our hypothesis, a signifi cant negative correlation between 17β-estradiol dose and infarct size was found (p=0.018). Thus, no support was found for the hypothesis that 17β-estradiol can be both neuroprotective and neurotoxic merely depending on dose. In fact, on the contrary, the fi ndings indicate that the higher the dose of 17β-estradiol, the smaller the infarct.

National Category
Clinical Medicine Microbiology in the medical area
Identifiers
urn:nbn:se:liu:diva-123890 (URN)
Available from: 2016-01-13 Created: 2016-01-13 Last updated: 2018-01-10Bibliographically approved
Kawa, L., Barde, S., Arborelius, U. P., Theodorsson, E., Agoston, D., Risling, M. & Hokfelt, T. (2016). Expression of galanin and its receptors are perturbed in a rodent model of mild, blast-induced traumatic brain injury. Experimental Neurology, 279, 159-167
Open this publication in new window or tab >>Expression of galanin and its receptors are perturbed in a rodent model of mild, blast-induced traumatic brain injury
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2016 (English)In: Experimental Neurology, ISSN 0014-4886, E-ISSN 1090-2430, Vol. 279, p. 159-167Article in journal (Refereed) Published
Abstract [en]

The symptomatology, mood and cognitive disturbances seen in post-traumatic stress disorder (PTSD) and mild blast-induced traumatic brain injury (mbTBI) overlap considerably. However the pathological mechanisms underlying the two conditions are currently unknown. The neuropeptide galanin has been suggested to play a role in the development of stress and mood disorders. Here we applied bio- and histochemical methods with the aim to elucidate the nature of any changes in the expression of galanin and its receptors in a rodent model of mbTBI. In situ hybridization and quantitative polymerase chain reaction studies revealed significant, injury induced changes, in some cases lasting at least for one week, in the mRNA levels of galanin and/or its three receptors, galanin receptor 1-3 (GalR1-3). Such changes were seen in several forebrain regions, and the locus coeruleus. In the ventral periaqueductal gray GalR1 mRNA levels were increased, while GalR2 were decreased. Analysis of galanin peptide levels using radioimmunoassay demonstrated an increase in several brain regions including the locus coeruleus, dorsal hippocampal formation and amygdala. These findings suggest a role for the galanin system in the endogenous response to mbTBI, and that pharmacological studies of the effects of activation or inhibition of different galanin receptors in combination with functional assays of behavioral recovery may reveal promising targets for new therapeutic strategies in mbTBI. (C) 2016 Elsevier Inc. All rights reserved.

Place, publisher, year, edition, pages
ACADEMIC PRESS INC ELSEVIER SCIENCE, 2016
Keywords
Anxiety; Cholecystokinin (CCK); Depression; Neuropeptide; Periaqueductal gray; Receptor; Transcriptional regulation; Translational regulation; Transmitter coexistence
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-128142 (URN)10.1016/j.expneurol.2016.02.019 (DOI)000374612900014 ()26928087 (PubMedID)
Note

Funding Agencies|Swedish Armed Forces RD [AF.9221006]; Swedish Research Council [04X-2887]; Karolinska Institutet Funds

Available from: 2016-05-19 Created: 2016-05-19 Last updated: 2017-11-30
Roth, L., Olsen Faresjö, Å., Theodorsson, E. & Jensen, P. (2016). Hair cortisol varies with season and lifestyle and relates to human interactions in German shepherd dogs. Scientific Reports, 6(19631)
Open this publication in new window or tab >>Hair cortisol varies with season and lifestyle and relates to human interactions in German shepherd dogs
2016 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, no 19631Article in journal (Refereed) Published
Abstract [en]

It is challenging to measure long-term endocrine stress responses in animals. We investigated whether cortisol extracted from dog hair reflected the levels of activity and stress long-term, during weeks and months. Hair samples from in total 59 German shepherds were analysed. Samples for measuring cortisol concentrations were collected at three occasions and we complemented the data with individual scores from the Canine Behavioural Assessment and Research Questionnaire (C-BARQ). Generalised linear mixed model (GLMM) results showed that hair cortisol varied with season and lifestyle: competition dogs had higher levels than companion, and professional working dogs, and levels were higher in January than in May and September. In addition, a positive correlation was found between the cortisol levels and the C-BARQ score for stranger-directed aggression (r = 0.31, P = 0.036). Interestingly, the factor "playing often with the dog" (r = -0.34, P = 0.019) and "reward with a treat/toy when the dog behaves correctly" (r = -0.37, P = 0.010) correlated negatively with cortisol levels, suggesting that positive human interactions reduce stress. In conclusion, hair cortisol is a promising method for revealing the activity of the HPA-axis over a longer period of time, and human interactions influence the cortisol level in dogs.

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP, 2016
National Category
Biological Sciences Basic Medicine Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-125147 (URN)10.1038/srep19631 (DOI)000368778700002 ()26791276 (PubMedID)
Note

Funding Agencies|Formas; European Research Council (ERC) [322206]; County Council of Ostergtland, Sweden

Available from: 2016-02-15 Created: 2016-02-15 Last updated: 2018-01-10
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