| 1. |
- Barmpatsalou, Vicky, et al.
(författare)
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Development and validation of a porcine artificial colonic mucus model reflecting the properties of native colonic mucus in pigs
- 2023
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier. - 0928-0987 .- 1879-0720. ; 181
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Tidskriftsartikel (refereegranskat)abstract
- Colonic mucus plays a key role in colonic drug absorption. Mucus permeation assays could therefore provide useful insights and support rational formulation development in the early stages of drug development. However, the collection of native colonic mucus from animal sources is labor-intensive, does not yield amounts that allow for routine experimentation, and raises ethical concerns. In the present study, we developed an in vitro porcine artificial colonic mucus model based on the characterization of native colonic mucus. The structural properties of the artificial colonic mucus were validated against the native secretion for their ability to capture key diffusion patterns of macromolecules in native mucus. Moreover, the artificial colonic mucus could be stored under common laboratory conditions, without compromising its barrier properties. In conclusion, the porcine artificial colonic mucus model can be considered a biorelevant way to study the diffusion behavior of drug candidates in colonic mucus. It is a cost-efficient screening tool easily incorporated into the early stages of drug development and it contributes to the implementation of the 3Rs (refinement, reduction, and replacement of animals) in the drug development process.
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| 2. |
- Barmpatsalou, Vicky, et al.
(författare)
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Physiological properties, composition and structural profiling of porcine gastrointestinal mucus
- 2021
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Ingår i: European journal of pharmaceutics and biopharmaceutics. - : Elsevier. - 0939-6411 .- 1873-3441. ; 169, s. 156-167
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Tidskriftsartikel (refereegranskat)abstract
- The gastrointestinal mucus is a hydrogel that lines the luminal side of the gastrointestinal epithelium, offering barrier protection from pathogens and lubrication of the intraluminal contents. These barrier properties likewise affect nutrients and drugs that need to penetrate the mucus to reach the epithelium prior to absorption. In order to assess the potential impact of the mucus on drug absorption, we need information about the nature of the gastrointestinal mucus. Today, most of the relevant available literature is mainly derived from rodent studies. In this work, we used a larger animal species, the pig model, to characterize the mucus throughout the length of the gastrointestinal tract. This is the first report of the physiological properties (physical appearance, pH and water content), composition (protein, lipid and metabolite content) and structural profiling (rheology and gel network) of the porcine gastrointestinal mucus. These findings allow for direct comparisons between the characteristics of mucus from various segments and can be further utilized to improve our understanding of the role of the mucus on region dependent drug absorption. Additionally, the present work is expected to contribute to the assessment of the porcine model as a preclinical species in the drug development process.
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| 3. |
- Dubbelboer, Ilse R, et al.
(författare)
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Gastrointestinal mucus in dog : Physiological characteristics, composition, and structural properties
- 2022
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Ingår i: European journal of pharmaceutics and biopharmaceutics. - : Elsevier. - 0939-6411 .- 1873-3441. ; 173, s. 92-102
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Tidskriftsartikel (refereegranskat)abstract
- Gastrointestinal (GI) mucus is continuously secreted and lines the entire length of the GI tract. Essential for health, it keeps the noxious luminal content away from the epithelium. Our aim was to characterize the composition and structure of mucus throughout the various GI segments in dog.Mucus was collected from the stomach, small intestine (duodenum, jejunum, ileum), and large intestine (cecum, proximal and distal colon) from dogs. Composition was determined by multi-omics. Structural properties were investigated using cryoSEM and rheology.GI mucus contained 74-95% water and maintained a pH around 6.5. The proteome was similar across the different GI segments. The highest abundant secreted gel-forming mucin in the gastric mucus was mucin 5AC, whether mucin 2 had highest abundance in the intestinal mucus. Lipid and metabolite abundance was generally higher in the jejunal mucus than the colonic mucus. CryoSEM microscopy revealed smaller pore size in small intestinal mucus, which increased in the large intestine. All mucus samples showed shear-thinning behavior and characteristics of gel-like structure.In conclusion, the mucus is a highly viscous and hydrated material. These data provide an important baseline for future studies on human and canine intestinal diseases and the dog model in drug absorption.
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| 4. |
- Karlson, Agnes M. L., et al.
(författare)
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Linking consumer physiological status to food-web structure and prey food value in the Baltic Sea
- 2020
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Ingår i: Ambio. - Stockholm : Springer Netherlands. - 0044-7447 .- 1654-7209. ; 49:2, s. 391-406
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Tidskriftsartikel (refereegranskat)abstract
- Declining physiological status in marine top consumers has been observed worldwide. We investigate changes in the physiological status and population/community traits of six consumer species/groups in the Baltic Sea (1993-2014), spanning four trophic levels and using metrics currently operational or proposed as indicators of food-web status. We ask whether the physiological status of consumers can be explained by food-web structure and prey food value. This was tested using partial least square regressions with status metrics for gray seal, cod, herring, sprat and the benthic predatory isopod Saduria as response variables, and abundance and food value of their prey, abundance of competitors and predators as predictors. We find evidence that the physiological status of cod, herring and sprat is influenced by competition, predation, and prey availability; herring and sprat status also by prey size. Our study highlights the need for management approaches that account for species interactions across multiple trophic levels.
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| 5. |
- Karlsson, Agnes
(författare)
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Jämförelser av olika kväveisotop-baserade metoder för att bestämma födovävsposition i torsk: betydelse för miljögiftsövervakning
- 2022
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Kväveisotoper (δ15N) kan ge information om var i födoväven en organism befinner sig. Detta eftersom den tyngre kväveisotopen anrikas likt miljögifter upp i födoväven. Inom miljögiftsövervakningen kan information om födovävsposition hjälpa till att förklara variationer i miljögiftshalter mellan år som inte nödvändigtvis reflekterar förändringar i belastningen. Födovävsposition används även i statusbedömningar av miljögiftshalter som baseras på miljökvalitetsnormer. Beräkningar av födovävsposition kan dock göras på flera sätt med hjälp av δ15N. Det vanligaste är bulk-analyser av δ15N från muskelvävnad i fisk som sedan normaliseras mot samma mätningar i en baslinjeorganism, vanligtvis blåmussla. En nyare metod är att analysera δ15N i enskilda aminosyror som extraheras från muskelvävnad i organismen av intresse, t.ex fisk och då behövs inte en baslinejorganism vilket är praktiskt eftersom dessa inte alltid är tillgängliga från samma plats och tid som fisken provtagits från. Det finns slutligen olika sätt att beräkna födovävsposition enligt aminosyrametoden beroende på vilka aminosyror som används. Denna studie jämför de estimat av födovävsposition som beräknas utifrån bulk-metoden med olika beräkningsvarianter av aminosyra-metoden (olika aminosyror som ingår) och jämför trenderna över tid. Metoderna skiljer sig i både absoluta värden och trender över tid och samtliga aminosyrametoder visar på ökningar över tid som inte nödvändigtvis reflekterar en reell ökning av födovävspositionen. Bulk-metoden underskattar istället födovävsposition jämfört med vad som är ekologiskt förväntat, men visar inte på ökning över tid. En av aminosyra-metoderna rekommenderas då de absoluta värdena är närmast födovävsposition 4 som är förväntat för torsk i denna storlek men anledningar till en ökning över tid behöver utredas vidare.
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| 6. |
- Sanchez Klose, Felix, 1989, et al.
(författare)
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The Pseudomonas aeruginosa lectin LecB modulates intracellular reactive oxygen species production in human neutrophils
- 2024
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Ingår i: European Journal of Immunology. - 0014-2980 .- 1521-4141. ; 54:2
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Tidskriftsartikel (refereegranskat)abstract
- Pseudomonas aeruginosa is a Gram-negative bacterium and an opportunistic pathogen ubiquitously present throughout nature. LecB, a fucose-, and mannose-binding lectin, is a prominent virulence factor of P. aeruginosa, which can be expressed on the bacterial surface but also be secreted. However, the LecB interaction with human immune cells remains to be characterized. Neutrophils comprise the first line of defense against infections and their production of reactive oxygen species (ROS) and release of extracellular traps (NETs) are critical antimicrobial mechanisms. When profiling the neutrophil glycome we found several glycoconjugates on granule and plasma membranes that could potentially act as LecB receptors. In line with this, we here show that soluble LecB can activate primed neutrophils to produce high levels of intracellular ROS (icROS), an effect that was inhibited by methyl fucoside. On the other hand, soluble LecB inhibits P. aeruginosa-induced icROS production. In support of that, during phagocytosis of wild-type and LecB-deficient P. aeruginosa, bacteria with LecB induced less icROS production as compared with bacteria lacking the lectin. Hence, LecB can either induce or inhibit icROS production in neutrophils depending on the circumstances, demonstrating a novel and potential role for LecB as an immunomodulator of neutrophil functional responses.
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| 7. |
- Sandvik, Ann-Helén, 1966-, et al.
(författare)
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Nursing students' experiences of peer learning in a dedicated educational unit in municipal home healthcare: A phenomenological study
- 2020
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Ingår i: Nordic journal of nursing research. - : SAGE Publications. - 2057-1585 .- 2057-1593.
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Tidskriftsartikel (refereegranskat)abstract
- The shift from hospital-based nursing care to municipal home healthcare has led to the provision of more diverse, complex and advanced nursing care in this context. This poses challenges for undergraduate nursing students’ clinical education. The aim of this study was to describe nursing students’ experiences of learning nursing care through peer learning in a dedicated educational unit in municipal home healthcare. Data were collected through interviews with seven nursing students. The analysis was based on a reflective lifeworld research approach. The study followed the COREQ checklist. Strong cooperation and feelings of safety were found to boost learning and encourage the students to challenge themselves. Alternating between an observational and an active role during independent home visits was beneficial for intertwining caring and learning. Further, being trusted to work independently increased their ethical orientation, knowledge, self-esteem and self-confidence.
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| 8. |
- Sundqvist, Martina, et al.
(författare)
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Severe chronic non-bacterial osteomyelitis in combination with total MPO deficiency and responsiveness to TNFα inhibition
- 2023
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Ingår i: Frontiers in Immunology. - : FRONTIERS MEDIA SA. - 1664-3224. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- We describe a female patient suffering from severe chronic non-bacterial osteomyelitis (CNO) with systemic inflammation and advanced malnutrition and complete deficiency of myeloperoxidase (MPO). CNO is a rare autoinflammatory bone disorder associated with dysregulation of the innate immune system. MPO deficiency is a genetic disorder with partial or complete absence of the phagocyte peroxidase MPO. MPO deficiency has no established clinical phenotype but reports indicate increased susceptibility to infection and chronic inflammation. The patient’s symptoms began at 10 years of age with pain in the thighs, systemic inflammation and malnutrition. She was diagnosed with CNO at 14 years of age. Treatment with nonsteroidal anti-inflammatory drugs, corticosteroids, bisphosphonates or IL1-receptor antagonists (anakinra) did not relieve the symptoms. However, the patient responded instantly and recovered from her clinical symptoms when treated with TNFα blockade (adalimumab). Three years after treatment initiation adalimumab was withdrawn, resulting in rapid symptom recurrence. When reintroducing adalimumab, the patient promptly responded and went into remission. In addition to clinical and laboratory profiles, neutrophil functions (reactive oxygen species, ROS; neutrophil extracellular traps, NETs; degranulation; apoptosis; elastase activity) were investigated both in a highly inflammatory state (without treatment) and in remission (on treatment). At diagnosis, neither IL1β, IL6, nor TNFα was significantly elevated in serum, but since TNFα blockade terminated the inflammatory symptoms, the disease was likely TNFα-driven. All neutrophil parameters were normal both during treatment and treatment withdrawal, except for MPO-dependent intracellular ROS- and NET formation. The role of total MPO deficiency for disease etiology and severity is discussed.
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