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  • 1.
    Ganda Mall, John Peter
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Löfvendahl, Lisa
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Lindqvist, Carl Mårten
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Brummer, Robert Jan
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Keita, Å. V.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Schoultz, Ida
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Differential effects of dietary fibres on colonic barrier function in elderly individuals with gastrointestinal symptoms2018Ingår i: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, nr 1, artikel-id 13404Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Gastrointestinal problems are common in elderly and often associated with psychological distress and increased levels of corticotrophin-releasing hormone, a hormone known to cause mast cell (MC) degranulation and perturbed intestinal barrier function. We investigated if dietary fibres (non-digestible polysaccharides [NPS]) could attenuate MC-induced colonic hyperpermeability in elderly with gastrointestinal (GI) symptoms. Colonic biopsies from elderly with diarrhoea and/or constipation (n = 18) and healthy controls (n = 19) were mounted in Ussing chambers and pre-stimulated with a yeast-derived beta (β)-glucan (0.5 mg/ml) or wheat-derived arabinoxylan (0.1 mg/ml) before the addition of the MC-degranulator Compound (C) 48/80 (10 ng/ml). Permeability markers were compared pre and post exposure to C48/80 in both groups and revealed higher baseline permeability in elderly with GI symptoms. β-glucan significantly attenuated C48/80-induced hyperpermeability in elderly with GI symptoms but not in healthy controls. Arabinoxylan reduced MC-induced paracellular and transcellular hyperpermeability across the colonic mucosa of healthy controls, but did only attenuate transcellular permeability in elderly with GI symptoms. Our novel findings indicate that NPS affect the intestinal barrier differently depending on the presence of GI symptoms and could be important in the treatment of moderate constipation and/or diarrhoea in elderly.

  • 2.
    Ganda Mall, John-Peter
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Non-digestible Polysaccharides and Intestinal Barrier Function: specific focus on its efficacy in elderly and patients with Crohn’s disease2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    A large number of elderly suffer from gastrointestinal (GI) symptoms such as constipation and diarrhoea. The underlying mechanisms of age-acquired GI symptoms are not well studied but are necessary to clarify in order to recommend the right treatment. Non-digestible polysaccharides (NPS) are dietary fibres that could have beneficial effects on the intestinal immune system and barrier function, although their efficacy needs to be evaluated. Paper I showed that elderly with GI symptoms have significantly higher small intestinal permeability than a general elderly population, along with a stronger association to psychological distress. In Paper II we performed a randomised controlled trial with a general population of elderly that consumed either placebo, the NPS’s arabinoxylan or oat β-glucan for a period of 6 weeks. No protective effects were observed related to indomethacin-induced intestinal hyperpermeability, inflammatory markers, or self-reported health if compared to placebo. Paper III showed that stimulation with a yeast-derived β-glucan significantly attenuated Compound (C) 48/80-induced hyperpermeability in colonic biopsies from elderly with GI symptoms mounted in Ussing chambers, but not in young healthy adults. Arabinoxylan attenuated only C48/80-induced transcellular permeability in elderly but both paracellular and transcellular permeability in young healthy adults. Paper IV showed that the same yeast-derived β-glucan from paper III could cross the epithelium of ileal tissues from patients with Crohn’s disease (CD) and non-CD controls, mounted in Ussing chambers, and attenuate C48/80-induced hyperpermeability. In conclusion, we found that elderly with GI symptoms display a deteriorated barrier function and that administration of selective NPS can have beneficial effect on intestinal permeability in selective populations.

    Delarbeten
    1. Are self-reported gastrointestinal symptoms among older adults associated with increased intestinal permeability and psychological distress?
    Öppna denna publikation i ny flik eller fönster >>Are self-reported gastrointestinal symptoms among older adults associated with increased intestinal permeability and psychological distress?
    Visa övriga...
    2018 (Engelska)Ingår i: BMC Geriatrics, ISSN 1471-2318, E-ISSN 1471-2318, Vol. 18, nr 1, artikel-id 75Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    BACKGROUND: Despite the substantial number of older adults suffering from gastrointestinal (GI) symptoms little is known regarding the character of these complaints and whether they are associated with an altered intestinal barrier function and psychological distress. Our aim was to explore the relationship between self-reported gut health, intestinal permeability and psychological distress among older adults.

    METHODS: Three study populations were included: 1) older adults with GI symptoms (n = 24), 2) a group of older adults representing the general elderly population in Sweden (n = 22) and 3) senior orienteering athletes as a potential model of healthy ageing (n = 27). Questionnaire data on gut-health, psychological distress and level of physical activity were collected. Intestinal permeability was measured by quantifying zonulin in plasma. The level of systemic and local inflammation was monitored by measuring C-reactive protein (CRP), hydrogen peroxide in plasma and calprotectin in stool samples. The relationship between biomarkers and questionnaire data in the different study populations was illustrated using a Principal Component Analysis (PCA).

    RESULTS: Older adults with GI symptoms displayed significantly higher levels of both zonulin and psychological distress than both general older adults and senior orienteering athletes. The PCA analysis revealed a separation between senior orienteering athletes and older adults with GI symptoms and showed an association between GI symptoms, psychological distress and zonulin.

    CONCLUSIONS: Older adults with GI symptoms express increased plasma levels of zonulin, which might reflect an augmented intestinal permeability. In addition, this group suffer from higher psychological distress compared to general older adults and senior orienteering athletes. This relationship was further confirmed by a PCA plot, which illustrated an association between GI symptoms, psychological distress and intestinal permeability.

    Ort, förlag, år, upplaga, sidor
    BioMed Central, 2018
    Nyckelord
    Older adults; Gastrointestinal symptoms; Intestinal barrier function; Psychological distress
    Nationell ämneskategori
    Geriatrik
    Identifikatorer
    urn:nbn:se:oru:diva-66053 (URN)10.1186/s12877-018-0767-6 (DOI)000428260300001 ()29554871 (PubMedID)2-s2.0-85044174344 (Scopus ID)
    Forskningsfinansiär
    KK-stiftelsen, 20110225
    Anmärkning

    Funding Agencies:

    Bo Rydins stiftelse  F0514 

    Faculty of Medicine and Health at Örebro University  

    Diarrheal Disease Research Centre, Linköping University  

    Tillgänglig från: 2018-03-27 Skapad: 2018-03-27 Senast uppdaterad: 2019-12-20Bibliografiskt granskad
    2. Effects of dietary fibres on indomethacin-induced intestinal permeability in elderly: A randomised placebo controlled parallel clinical trial
    Öppna denna publikation i ny flik eller fönster >>Effects of dietary fibres on indomethacin-induced intestinal permeability in elderly: A randomised placebo controlled parallel clinical trial
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Annan medicinsk grundvetenskap
    Identifikatorer
    urn:nbn:se:oru:diva-66863 (URN)
    Tillgänglig från: 2018-05-04 Skapad: 2018-05-04 Senast uppdaterad: 2019-12-20Bibliografiskt granskad
    3. Differential effects of dietary fibres on colonic barrier function in elderly individuals with gastrointestinal symptoms
    Öppna denna publikation i ny flik eller fönster >>Differential effects of dietary fibres on colonic barrier function in elderly individuals with gastrointestinal symptoms
    Visa övriga...
    (Engelska)Manuskript (preprint) (Övrigt vetenskapligt)
    Nationell ämneskategori
    Annan medicinsk grundvetenskap
    Identifikatorer
    urn:nbn:se:oru:diva-66866 (URN)
    Tillgänglig från: 2018-05-04 Skapad: 2018-05-04 Senast uppdaterad: 2018-05-04Bibliografiskt granskad
    4. A β-Glucan-Based Dietary Fiber Reduces Mast Cell-Induced Hyperpermeability in Ileum From Patients With Crohn's Disease and Control Subjects
    Öppna denna publikation i ny flik eller fönster >>A β-Glucan-Based Dietary Fiber Reduces Mast Cell-Induced Hyperpermeability in Ileum From Patients With Crohn's Disease and Control Subjects
    Visa övriga...
    2017 (Engelska)Ingår i: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 24, nr 1, s. 166-178Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Background: Administration of β-glucan has shown immune-enhancing effects. Our aim was to investigate whether β-glucan could attenuate mast cell (MC)-induced hyperpermeability in follicle-associated epithelium (FAE) and villus epithelium (VE) of patients with Crohn's disease (CD) and in noninflammatory bowel disease (IBD)-controls. Further, we studied mechanisms of β-glucan uptake and effects on MCs in vitro.

    Methods: Segments of FAE and VE from 8 CD patients and 9 controls were mounted in Ussing chambers. Effects of the MC-degranulator compound 48/80 (C48/80) and yeast-derived β-1,3/1,6 glucan on hyperpermeability were investigated. Translocation of β-glucan and colocalization with immune cells were studied by immunofluorescence. Caco-2-cl1- and FAE-cultures were used to investigate β-glucan-uptake using endocytosis inhibitors and HMC-1.1 to study effects on MCs.

    Results: β-glucan significantly attenuated MC-induced paracellular hyperpermeability in CD and controls. Transcellular hyperpermeability was only significantly attenuated in VE. Baseline paracellular permeability was higher in FAE than VE in both groups, P<0.05, and exhibited a more pronounced effect by C48/80 and β-glucan P<0.05. No difference was observed between CD and controls. In vitro studies showed increased passage, P<0.05, of β-glucan through FAE-culture compared to Caco-2-cl1. Passage was mildly attenuated by the inhibitor methyl-β-cyclodextrin. HMC-1.1 experiments showed a trend to decreasing MC-degranulation and levels of TNF-α but not IL-6 by β-glucan. Immunofluorescence revealed more β-glucan-uptake and higher percentage of macrophages and dendritic cells close to β-glucan in VE of CD compared to controls.

    Conclusions: We demonstrated beneficial effects of β-glucan on intestinal barrier function and increased β-glucan-passage through FAE model. Our results provide important and novel knowledge on possible applications of β-glucan in health disorders and diseases characterized by intestinal barrier dysfunction.

    Ort, förlag, år, upplaga, sidor
    Lippincott-Raven Publishers, 2017
    Nyckelord
    Crohn’s disease, intestinal permeability, β-glucan
    Nationell ämneskategori
    Gastroenterologi
    Identifikatorer
    urn:nbn:se:oru:diva-63994 (URN)10.1093/ibd/izx002 (DOI)000427524400018 ()29272475 (PubMedID)
    Forskningsfinansiär
    Stiftelsen för strategisk forskning (SSF), RB13-016Vetenskapsrådet, 2014-02537
    Anmärkning

    Funding Agency:

    LIONS research foundation

    Tillgänglig från: 2018-01-09 Skapad: 2018-01-09 Senast uppdaterad: 2018-08-13Bibliografiskt granskad
  • 3.
    Ganda Mall, John-Peter
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Casado-Bedmar, Maite
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Winberg, Martin E.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Brummer, Robert Jan
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Schoultz, Ida
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Keita, Åsa V.
    A β-Glucan-Based Dietary Fiber Reduces Mast Cell-Induced Hyperpermeability in Ileum From Patients With Crohn's Disease and Control Subjects2017Ingår i: Inflammatory Bowel Diseases, ISSN 1078-0998, E-ISSN 1536-4844, Vol. 24, nr 1, s. 166-178Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Administration of β-glucan has shown immune-enhancing effects. Our aim was to investigate whether β-glucan could attenuate mast cell (MC)-induced hyperpermeability in follicle-associated epithelium (FAE) and villus epithelium (VE) of patients with Crohn's disease (CD) and in noninflammatory bowel disease (IBD)-controls. Further, we studied mechanisms of β-glucan uptake and effects on MCs in vitro.

    Methods: Segments of FAE and VE from 8 CD patients and 9 controls were mounted in Ussing chambers. Effects of the MC-degranulator compound 48/80 (C48/80) and yeast-derived β-1,3/1,6 glucan on hyperpermeability were investigated. Translocation of β-glucan and colocalization with immune cells were studied by immunofluorescence. Caco-2-cl1- and FAE-cultures were used to investigate β-glucan-uptake using endocytosis inhibitors and HMC-1.1 to study effects on MCs.

    Results: β-glucan significantly attenuated MC-induced paracellular hyperpermeability in CD and controls. Transcellular hyperpermeability was only significantly attenuated in VE. Baseline paracellular permeability was higher in FAE than VE in both groups, P<0.05, and exhibited a more pronounced effect by C48/80 and β-glucan P<0.05. No difference was observed between CD and controls. In vitro studies showed increased passage, P<0.05, of β-glucan through FAE-culture compared to Caco-2-cl1. Passage was mildly attenuated by the inhibitor methyl-β-cyclodextrin. HMC-1.1 experiments showed a trend to decreasing MC-degranulation and levels of TNF-α but not IL-6 by β-glucan. Immunofluorescence revealed more β-glucan-uptake and higher percentage of macrophages and dendritic cells close to β-glucan in VE of CD compared to controls.

    Conclusions: We demonstrated beneficial effects of β-glucan on intestinal barrier function and increased β-glucan-passage through FAE model. Our results provide important and novel knowledge on possible applications of β-glucan in health disorders and diseases characterized by intestinal barrier dysfunction.

  • 4.
    Ganda Mall, John-Peter
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Fart, Frida
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Sabet, Julia
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Lindqvist, Carl-Mårten
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Keita, Åsa V.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Brummer, Robert J.
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Schoultz, Ida
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Effects of dietary fibres on indomethacin-induced intestinal permeability in elderly: A randomised placebo controlled parallel clinical trialManuskript (preprint) (Övrigt vetenskapligt)
  • 5.
    Ganda Mall, John-Peter
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Löfvendahl, Lisa
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Brummer, Robert Jan
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Keita, Åsa V.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Schoultz, Ida
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Differential effects of dietary fibres on colonic barrier function in elderly individuals with gastrointestinal symptomsManuskript (preprint) (Övrigt vetenskapligt)
  • 6.
    Ganda Mall, John-Peter
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Östlund-Lagerström, Lina
    Department of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; Nutrition and Physical Activity Research Centre, Department of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Lindqvist, Carl Mårten
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Algilani, Samal
    Örebro universitet, Institutionen för hälsovetenskaper.
    Rasoal, Dara
    Örebro universitet, Institutionen för hälsovetenskaper.
    Repsilber, Dirk
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Brummer, Robert Jan
    Örebro universitet, Institutionen för medicinska vetenskaper.
    V. Keita, Åsa
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Schoultz, Ida
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Are self-reported gastrointestinal symptoms among older adults associated with increased intestinal permeability and psychological distress?2018Ingår i: BMC Geriatrics, ISSN 1471-2318, E-ISSN 1471-2318, Vol. 18, nr 1, artikel-id 75Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Despite the substantial number of older adults suffering from gastrointestinal (GI) symptoms little is known regarding the character of these complaints and whether they are associated with an altered intestinal barrier function and psychological distress. Our aim was to explore the relationship between self-reported gut health, intestinal permeability and psychological distress among older adults.

    METHODS: Three study populations were included: 1) older adults with GI symptoms (n = 24), 2) a group of older adults representing the general elderly population in Sweden (n = 22) and 3) senior orienteering athletes as a potential model of healthy ageing (n = 27). Questionnaire data on gut-health, psychological distress and level of physical activity were collected. Intestinal permeability was measured by quantifying zonulin in plasma. The level of systemic and local inflammation was monitored by measuring C-reactive protein (CRP), hydrogen peroxide in plasma and calprotectin in stool samples. The relationship between biomarkers and questionnaire data in the different study populations was illustrated using a Principal Component Analysis (PCA).

    RESULTS: Older adults with GI symptoms displayed significantly higher levels of both zonulin and psychological distress than both general older adults and senior orienteering athletes. The PCA analysis revealed a separation between senior orienteering athletes and older adults with GI symptoms and showed an association between GI symptoms, psychological distress and zonulin.

    CONCLUSIONS: Older adults with GI symptoms express increased plasma levels of zonulin, which might reflect an augmented intestinal permeability. In addition, this group suffer from higher psychological distress compared to general older adults and senior orienteering athletes. This relationship was further confirmed by a PCA plot, which illustrated an association between GI symptoms, psychological distress and intestinal permeability.

  • 7.
    König, Julia
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Ganda-Mall, John-Peter
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Rangel, Ignacio
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Edebol-Carlman, Hanna
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Brummer, Robert Jan
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    The Role of the Gut Microbiota in Brain Function2015Ingår i: Probiotics and Prebiotics: Current Research and Future Trends / [ed] Koen Venema & Ana Paula do Carmo, Poole, UK: Caister Academic Press, 2015Kapitel i bok, del av antologi (Refereegranskat)
  • 8.
    Rangel, Ignacio
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Ganda Mall, John Peter
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Roger, Willén
    Department of Pathology and Cytology, Uppsala University Hospital, Uppsala, Sweden.
    Sjöberg, Fei
    Department of Infectious Diseases, Institute of Biomedicine, University of Gothenburg, Göteborg, Sweden.
    Hultgren-Hörnquist, Elisabeth
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Degree of colitis correlates with microbial composition and cytokine responses in colon and caecum of Gαi2-deficient mice2016Ingår i: FEMS Microbiology Ecology, ISSN 0168-6496, E-ISSN 1574-6941, Vol. 92, nr 7, artikel-id fiw098Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    An altered immune response and gut microbiota have been associated with the pathology of Inflammatory Bowel Diseases (IBD). However, there is limited knowledge of how inflammation is associated with changes in the microbiota. We studied the microbiota in the intestine and faeces as well as the cytokine gene expressions in caecum and colon of a mouse model (Gαi2(-/-)) of colitis, and analysed them in relation to the degrees of inflammation in the colon. The degree of colitis was associated with general changes in the complexity of the microbiota and was corroborated by quantitative analyses of the Bacteroides and Lactobacillus High gene expression levels of IL-17 and IFN-γ in colon and caecum were detected in Gαi2(-/-) mice with moderate and severe colitis. High IL-27 gene expression in the colon of mice with moderate and severe colitis and in the caecum of mice with moderate colitis was also detected. Negative correlations between IL-27 and Bacteroides and Lactobacillus and between IFN-γ and Lactobacillus were detected in caecum. This research indicates that the degree of colitis in IBD correlates with the gene expression of cytokines and with disturbances in the gut microbiota. Furthermore, the caecum could have an important role in the pathology of IBD.

  • 9.
    Rangel, Ignacio
    et al.
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Ganda-Mall, John-Peter
    Örebro universitet, Institutionen för hälsovetenskap och medicin.
    Sjöberg, F.
    University of Gothenburg, Gothenburg, Sweden.
    Willen, R.
    Univ Uppsala Hosp, Uppsala, Sweden.
    Hultgren-Hörnquist, Elisabeth
    Örebro universitet, Institutionen för läkarutbildning.
    Alterations in gut microbiota composition in tissues and feces of G alpha i2(-/-) mice with colitis in parallel with enhanced cytokine secretion2013Ingår i: Immunology, ISSN 0019-2805, E-ISSN 1365-2567, Vol. 140, s. 168-169Artikel i tidskrift (Övrigt vetenskapligt)
  • 10.
    Östlund-Lagerström, Lina
    et al.
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Ganda Mall, John-Peter
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Algilani, Samal
    Örebro universitet, Institutionen för hälsovetenskaper.
    Rasoal, Dara
    Örebro universitet, Institutionen för hälsovetenskaper.
    Brummer, Robert Jan
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Schoultz, Ida
    Örebro universitet, Institutionen för medicinska vetenskaper.
    Low levels of inflammation and oxidative stress in senior orienteering athletesManuskript (preprint) (Övrigt vetenskapligt)
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