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Ilbäck, Nils-Gunnar
Publications (10 of 24) Show all publications
Edvinsson, M., Tallkvist, J., Nyström-Rosander, C. & Ilbäck, N.-G. (2017). Cholesterol uptake in the mouse aorta increases during Chlamydia pneumoniae infection. Pathogens and Disease, 75(1), Article ID ftx004.
Open this publication in new window or tab >>Cholesterol uptake in the mouse aorta increases during Chlamydia pneumoniae infection
2017 (English)In: Pathogens and Disease, E-ISSN 2049-632X, Vol. 75, no 1, article id ftx004Article in journal (Refereed) Published
Abstract [en]

Chlamydia pneumoniae has been suggested as a stimulator of the atherosclerotic process. Mice fed a normal diet were infected intranasally with C. pneumoniae and given one intraperitoneal injection of C-14-cholesterol tracer per day for 12 days. Bacteria were demonstrated in the aorta in the early phase of infection and in lungs and liver throughout the study period of 20 days. C-14-cholesterol was not affected in the heart but increased in the blood, liver and aorta on day 4 when the infection was clinically most severe. Furthermore, on day 20 C-14-cholesterol tended to be increased in the aorta. Accordingly, copper-and zinc levels and expressions of the infection biomarkers Cxcl2 and Ifng increased in the liver on day 4 with a tendency of increased of copper, zinc and Ifng on day 20. In mice where bacteria could be cultivated from the lungs, expressions of cholesterol transporters Abca1 and Idol were both increased in the liver on day 4. The increased levels of C-14-cholesterol in blood and aorta together with increased Abca1 and Idol in the liver during C. pneumoniae infection in mice fed a normal diet suggest that this pathogen may have a role in the initiation of the atherosclerotic process.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2017
Keywords
Chlamydia pneumoniae, atherosclerosis, cholesterol, Idol, Abca1, Cxcl2, interferon gamma, mouse, copper, zinc
National Category
Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-320821 (URN)10.1093/femspd/ftx004 (DOI)000398086700008 ()28158541 (PubMedID)
Funder
Swedish Research Council Formas
Available from: 2017-04-26 Created: 2017-04-26 Last updated: 2019-03-11Bibliographically approved
Edvinsson, M., Tallkvist, J., Nyström-Rosander, C. & Ilbäck, N.-G. (2017). Iron Homeostasis in Tissues Is Affected during Persistent Chlamydia pneumoniae Infection in Mice. BioMed Research International, Article ID 3642301.
Open this publication in new window or tab >>Iron Homeostasis in Tissues Is Affected during Persistent Chlamydia pneumoniae Infection in Mice
2017 (English)In: BioMed Research International, ISSN 2314-6133, E-ISSN 2314-6141, article id 3642301Article in journal (Refereed) Published
Abstract [en]

Chlamydia pneumoniae (C. pneumoniae) may be a mediator in the pathogenesis of atherosclerosis. For its growth C. pneumoniae depends on iron (Fe), but how Fe changes in tissues during persistent infection or affects bacterial replication in tissues is unknown. C. pneumoniae-infected C57BL/6J mice were sacrificed on days 4, 8, 20, and 40. Mice had bacteria in the lungs and liver on all days. Inflammatory markers, chemokine Cxcl2 and interferon-gamma, were not affected in the liver on day 40. The copper (Cu)/zinc (Zn) ratio in serum, another marker of infection/inflammation, increased on day 4 and tended to increase again on day 40. The Fe markers, transferrin receptor (TfR), Hepcidin (Hamp1), and ferroportin 1 (Fpn1), increased in the liver on day 4 and then normalized except for TfR that tended to decrease. TfR responses were similar to Fe in serum that increased on day 4 but tended to decrease thereafter. In the liver, Fe was increased on day 4 and also on day 40. The reappearing increases in Cu/Zn on day 40 concomitant with the increase in liver Fe on day 40, even though TfR tended to decrease, and the fact that viable C. pneumoniae was present in the lungs and liver may indicate the early phase of activation of recurrent infection.

Place, publisher, year, edition, pages
Hindawi Publishing Corporation, 2017
Keywords
TRACE-ELEMENT CHANGES; REAL-TIME PCR; MYOCARDIAL-INFARCTION; ATHEROSCLEROSIS; DISEASE; RISK; PATHOGENESIS; INFLAMMATION; EXPRESSION; COPPER
National Category
Infectious Medicine
Identifiers
urn:nbn:se:uu:diva-328277 (URN)10.1155/2017/3642301 (DOI)000403369400001 ()
Funder
Swedish Research Council Formas
Available from: 2017-11-10 Created: 2017-11-10 Last updated: 2019-03-11Bibliographically approved
Hammerling, U., Laurila, J. B., Grafstrom, R. & Ilbäck, N.-G. (2016). Consumption of Red/Processed Meat and Colorectal Carcinoma: Possible Mechanisms Underlying the Significant Association. Critical reviews in food science and nutrition, 56(4), 614-634
Open this publication in new window or tab >>Consumption of Red/Processed Meat and Colorectal Carcinoma: Possible Mechanisms Underlying the Significant Association
2016 (English)In: Critical reviews in food science and nutrition, ISSN 1040-8398, E-ISSN 1549-7852, Vol. 56, no 4, p. 614-634Article, review/survey (Refereed) Published
Abstract [en]

Epidemiology and experimental studies provide an overwhelming support of the notion that diets high in red or processed meat accompany an elevated risk of developing pre-neoplastic colorectal adenoma and frank colorectal carcinoma (CRC). The underlying mechanisms are disputed; thus several hypotheses have been proposed. A large body of reports converges, however, on haem and nitrosyl haem as major contributors to the CRC development, presumably acting through various mechanisms. Apart from a potentially higher intestinal mutagenic load among consumers on a diet rich in red/processed meat, other mechanisms involving subtle interference with colorectal stem/progenitor cell survival or maturation are likewise at play. From an overarching perspective, suggested candidate mechanisms for red/processed meat-induced CRC appear as three partly overlapping tenets: (i) increased N-nitrosation/oxidative load leading to DNA adducts and lipid peroxidation in the intestinal epithelium, (ii) proliferative stimulation of the epithelium through haem or food-derived metabolites that either act directly or subsequent to conversion, and (iii) higher inflammatory response, which may trigger a wide cascade of pro-malignant processes. In this review, we summarize and discuss major findings of the area in the context of potentially pertinent mechanisms underlying the above-mentioned association between consumption of red/processed meat and increased risk of developing CRC.

Keywords
Dietary patterns, red/processed meat, intestinal carcinogenesis, morphogenetic pathways, haem, nitrosyl-haem, N-nitroso compounds, fat peroxidation
National Category
Nutrition and Dietetics Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-299091 (URN)10.1080/10408398.2014.972498 (DOI)000373125300005 ()25849747 (PubMedID)
Available from: 2016-07-14 Created: 2016-07-14 Last updated: 2017-11-28Bibliographically approved
Edvinsson, M., Ilbäck, N.-G., Frisk, P., Thelin, S. & Nyström-Rosander, C. (2016). Trace Element Changes in Thoracic Aortic Dissection. Biological Trace Element Research, 169(2), 159-163
Open this publication in new window or tab >>Trace Element Changes in Thoracic Aortic Dissection
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2016 (English)In: Biological Trace Element Research, ISSN 0163-4984, E-ISSN 1559-0720, Vol. 169, no 2, p. 159-163Article in journal (Refereed) Published
Abstract [en]

Thoracic aortic dissection is a life-threatening condition with an incompletely understood pathogenesis. Trace elements are essential for the functioning of different processes in the body, including the immune system and associated responses to infection/inflammation. Because inflammation may be part of the pathogenesis of thoracic aortic dissection, we investigated whether trace element changes associated with inflammation occur in serum and tissue samples during the disease. The study included 21 patients undergoing surgery for thoracic aortic dissection, 10 forensic autopsy specimens for tissue controls and 23 healthy blood donors for serum controls. Levels of magnesium (Mg), calcium (Ca), vanadium (V), manganese (Mn), iron (Fe), cobalt (Co), copper (Cu), zinc (Zn), arsenic (As), selenium (Se), cadmium (Cd) and mercury (Hg) were measured in the aortic tissue and serum by inductively coupled plasma-mass spectrometry (ICP-MS). In the serum, Ca, V, Cu and Zn decreased, whereas Fe increased. In the tissue, Cu and Zn decreased and Fe tended to increase. The Cu/Zn ratio in the serum, a marker of infection/inflammation, did not change in the patients. Concerning trace element changes in the serum and tissue, our data do not support the hypothesis that inflammation is involved in the pathogenesis of thoracic aortic dissection.

National Category
Endocrinology and Diabetes Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:uu:diva-266501 (URN)10.1007/s12011-015-0432-2 (DOI)000368366400002 ()26152852 (PubMedID)
Funder
Swedish Research Council Formas
Available from: 2015-11-10 Created: 2015-11-10 Last updated: 2019-03-11Bibliographically approved
Aspenstrom-Fagerlund, B., Tallkvist, J., Ilbäck, N.-G. & Glynn, A. W. (2015). Oleic acid increases intestinal absorption of the BCRP/ABCG2 substrate, mitoxantrone, in mice. Toxicology Letters, 237(2), 133-139
Open this publication in new window or tab >>Oleic acid increases intestinal absorption of the BCRP/ABCG2 substrate, mitoxantrone, in mice
2015 (English)In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 237, no 2, p. 133-139Article in journal (Refereed) Published
Abstract [en]

The efflux transporter breast cancer resistance protein (BCRP/ABCG2) decrease intestinal absorption of many food toxicants. Oleic acid increases absorption of the specific BCRP substrate mitoxantrone (MXR), and also BCRP gene expression in human intestinal Caco-2 cells, suggesting that oleic acid affect the BCRP function. Here, we investigated the effect of oleic acid on intestinal absorption of MXR in mice. Mice were orally dosed with 2.4 g oleic acid/kg b.w. and 1 mg MXR/kg b.w., and sacrificed 30, 60, 90 or 120 min after exposure, or were exposed to 0.6, 2.4 or 4.8 g oleic acid/kg b.w. and 1mg MXR/kg b.w., and sacrificed 90 min after exposure. Mice were also treated with Ko143 together with MXR and sacrificed after 60 min, as a positive control of BCRP-mediated effects on MXR absorption. Absorption of MXR increased after exposure to oleic acid at all doses, and also after exposure to Ko143. Intestinal BCRP gene expression tended to increase 120 min after oleic acid exposure. Our results in mice demonstrate that oleic acid decreases BCRP-mediated efflux, causing increased intestinal MXR absorption in mice. These findings may have implications in humans, concomitantly exposed to oleic acid and food contaminants that, similarly as MXR, are substrates of BCRP.

Keywords
Oleic acid, BCRP, Mitoxantrone, FVB mice, Intestinal absorption
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:uu:diva-259082 (URN)10.1016/j.toxlet.2015.06.009 (DOI)000357391500008 ()26071310 (PubMedID)
Available from: 2015-07-29 Created: 2015-07-27 Last updated: 2018-01-11Bibliographically approved
Lundgren, M., Darnerud, P. O. & Ilbäck, N.-G. (2013). The flame-retardant BDE-99 dose-dependently affects viral replication in CVB3-infected mice. Chemosphere, 91(10), 1434-1438
Open this publication in new window or tab >>The flame-retardant BDE-99 dose-dependently affects viral replication in CVB3-infected mice
2013 (English)In: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 91, no 10, p. 1434-1438Article in journal (Refereed) Published
Abstract [en]

The flame retardant component 2,2',4,4',5-penta-BDE (BDE-99) is found in the environment and in human tissues and fluids. In mice the common human coxsackievirus B3 (CVB3) infection has been shown to change the tissue distribution of BDE-99. We now investigate how CVB3 infection in mice affects liver uptake of C-14 at two doses of radiolabelled BDE-99, and whether increased tissue levels are related to changed virus replication and gene expression of the proinflammatory chemokine monocyte chemoattractant protein-1 (MCP-1). Mice were infected on day 0, orally treated either with 200 mu g or 20 mg C-14-BDE-99/kg bw on day 1, and euthanised on day 3. Serum and liver levels of C-14-BDE-99, as well as virus levels and gene expressions of MCP-1 in the liver, were measured. In non-infected mice, there was a dose-dependent uptake of BDE-99 in both liver and serum, and in infected animals the liver BDE-99 levels was further increased. When comparing infected mice exposed to the two BDE-99 doses, the higher BDE dose resulted in increased virus amounts in the liver, and decreased infection-induced expression of MCP-1. Consequently, a high enough dose/tissue concentration of BDE-99 may result in a disturbed mobilisation of immune cells into infected tissues that could explain higher virus titres and a possibly altered clinical course of the disease. Moreover, the fact that CVB3 infection increased the BDE-99 levels in liver but not in serum may impair the risk assessment of polybrominated diphenyl ethers (PBDEs) in subclinical and clinically infected individuals, as serum levels is the common marker of exposure. 

Keywords
PBDE, Coxsackievirus B3, Tissue distribution, Virus levels, MCP-1
National Category
Natural Sciences Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-202897 (URN)10.1016/j.chemosphere.2013.01.044 (DOI)000319094200008 ()
Available from: 2013-07-01 Created: 2013-07-01 Last updated: 2017-12-06Bibliographically approved
Abramsson-Zetterberg, L. & Ilbäck, N.-G. (2013). The synthetic food colouring agent Allura Red AC (E129) is not genotoxic in a flow cytometry-based micronucleus assay in vivo. Food and Chemical Toxicology, 59, 86-89
Open this publication in new window or tab >>The synthetic food colouring agent Allura Red AC (E129) is not genotoxic in a flow cytometry-based micronucleus assay in vivo
2013 (English)In: Food and Chemical Toxicology, ISSN 0278-6915, E-ISSN 1873-6351, Vol. 59, p. 86-89Article in journal (Refereed) Published
Abstract [en]

The safety of several azo colouring agents, used as food additives, has during the years been questioned. Allura Red AC (E129) has in some publications been classified as genotoxic. In fact, in the European Union, Allura Red is permitted as a food additive in human food, but, surprisingly, it was not acceptable as an additive for use in animal feed. In this study we have evaluated whether Allura Red is genotoxic using a flow cytometer-based micronucleus assay in peripheral blood of mice. Male FVB mice were given a single intra-peritoneal injection of various doses of Allura Red and sacrificed at 46 h after treatment. The tested doses were 0, 100, 200, 400, 600, 800, 1000, 1500, and 2000 mg/kg body weight (b.w.). Each dose group constituted three mice, except for in the dose group of 1000 mg/kg b.w., which constituted four mice. Blood samples were collected and the frequency of micronucleated polychromatic erythrocytes (fMNPCE) and the cell proliferation (%PCE) was determined. The analyses did not show any significant difference in the %PCE or in the fMNPCE. Consequently, under the testing circumstances one can conclude that Allura Red is not genotoxic.

Keywords
Allura Red, Azo dyes, E129, Micronucleus test, Chromosome aberration
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-209486 (URN)10.1016/j.fct.2013.05.047 (DOI)000324280000011 ()
Available from: 2013-10-21 Created: 2013-10-21 Last updated: 2017-12-06Bibliographically approved
Aspenström-Fagerlund, B., Tallkvist, J., Ilbäck, N.-G. & Glynn, A. W. (2012). Oleic acid decreases BCRP mediated efflux of mitoxantrone in Caco-2 cell monolayers. Food and Chemical Toxicology, 50(10), 3635-3645
Open this publication in new window or tab >>Oleic acid decreases BCRP mediated efflux of mitoxantrone in Caco-2 cell monolayers
2012 (English)In: Food and Chemical Toxicology, ISSN 0278-6915, E-ISSN 1873-6351, Vol. 50, no 10, p. 3635-3645Article in journal (Refereed) Published
Abstract [en]

Breast cancer resistance protein (BCRP) efflux restricts intestinal absorption of substances like heterocyclic amines, mycotoxins and certain human and veterinary drugs. Fat rich meals seem to increase absorption of drugs which are BCRP substrates or inhibitors. We therefore hypothesize that absorption of toxicants normally effluxed by BCRP are increased by fatty acids in food. Transport across and accumulation of H-3-Mitoxantrone (MXR) in Caco-2 cell monolayers were measured after 60 min exposure to emulsions of H-3-MXR (1 mu M) and oleic acid (0.5-5 mM). In addition, BCRP gene expression (RT-PCR) and the amount of BCRP protein (Western blot) were measured in oleic acid exposed Caco-2 cells. Oleic acid increased transport of MXR in a concentration dependent manner and 2 mM oleic acid or higher increased accumulation of MXR in cells, without any signs of cytotoxicity. Gene expression of BCRP was increased after exposure to oleic acid for 6 h, but the amount of BCRP protein was not increased. In conclusion, oleic acid clearly induced BCRP gene expression and reduced BCRP mediated efflux, although the amount of BCRP in cells was not affected. Consequently, effects of fatty acids on BCRP mediated efflux are important to consider in risk assessment of toxicants in food.

Keywords
Oleic acid, BCRP, Mitoxantrone, Ko143, Caco-2 cell monolayers
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-187721 (URN)10.1016/j.fct.2012.07.015 (DOI)000309897100035 ()
Available from: 2012-12-11 Created: 2012-12-10 Last updated: 2017-12-07Bibliographically approved
Ilbäck, N.-G., Siller, M. & Stålhandske, T. (2008). Effects of buprenorphine on body temperature, locomotor activity and cardiovascular function when assessed by telemetric monitoring in rats. Laboratory Animals. Journal of the Laboratory Animal Science Association, 42(2), 149-160
Open this publication in new window or tab >>Effects of buprenorphine on body temperature, locomotor activity and cardiovascular function when assessed by telemetric monitoring in rats
2008 (English)In: Laboratory Animals. Journal of the Laboratory Animal Science Association, ISSN 0023-6772, E-ISSN 1758-1117, Vol. 42, no 2, p. 149-160Article in journal (Refereed) Published
Abstract [en]

Buprenorphine is a potent analgesic commonly used clinically in humans and rodents experiencing severe pain. However, effects of therapeutic doses on locomotor activity and the cardiovascular system have not been studied in conscious animals. The effects of buprenorphine were therefore evaluated in this study using telemetric monitoring in conscious animals. Telemetry transmitters were implanted in the peritoneal cavity of Wistar rats with a pressure catheter in the aorta and electrodes for electrocardiogram (ECG) recording subcutaneously. After a single subcutaneous administration of saline, each rat was administered single subcutaneous doses of 0.006, 0.03 or 0.15 mg/kg body weight (bw) of buprenorphine. During a 10 h period after administration, buprenorphine induced a varying dose-dependent increase in body temperature, heart rate, dP/dt and systolic-diastolic blood pressure, as well as a corresponding decrease in QT time. At high dose, however, QT time was still decreased 24 h post-administration, but no arrhythmias or visual changes were observed in the ECG complex. Body temperature and heart rate increased at the high dose of buprenorphine, even at 20-24 h after administration. Moreover, the high dose of buprenorphine induced a biphasic response in diastolic blood pressure, with an early and pronounced increase that, at 14 h after administration, reversed to a decrease, failing to normalize within 24 h post-dosage. The results indicate that buprenorphine induces long-lasting effects (such as body temperature and cardiovascular effects) in the rat after a single subcutaneous dose at 0.15 mg/kg bw.

Keywords
Buprenorphine, cardiovascular function, telemetry
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-17561 (URN)10.1258/la.2007.06002e (DOI)000255979900004 ()18435873 (PubMedID)
Available from: 2008-07-10 Created: 2009-02-06 Last updated: 2017-12-08Bibliographically approved
Frisk, P., Molin, Y. & Ilbäck, N.-G. (2008). Tissue uptake of mercury is changed during the course of a common viral infection in mice. Environmental Research, 106(2), 178-184
Open this publication in new window or tab >>Tissue uptake of mercury is changed during the course of a common viral infection in mice
2008 (English)In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 106, no 2, p. 178-184Article in journal (Refereed) Published
Abstract [en]

Mercury (Hg) has been shown to have immunotoxic effects and to influence the severity of infection. However, the impact of infection on the normal Hg homeostasis in different target organs involved in the disease process has not been studied. In this study, Hg was measured through inductively coupled plasma-mass spectrometry (ICP-MS) in the intestine, serum, liver, and brain on days 3, 6, and 9 of coxsackievirus B3 (CVB3) infection in female Balb/c mice. The severity of the infection was assessed from clinical signs of disease and the number of virus particles in infected organs. CVB3 and gene expression of metallothionein 1 (MT1) was measured by reverse transcription-polymerase chain reaction (RT-PCR). Gene expression of MT1 increased and peaked on day 3 in the brain (93%, p<0.01) and liver (19-fold, p<0.01) and on day 6 in the intestine (seven-fold, p<0.01). This peak in MT1 in the liver and brain corresponded to the peak in virus numbers in these tissues. Hg in the intestine and serum tended to decrease on all days of infection. The maximum decrease, in comparison with non-infected mice, occurred in the intestine (78%, p<0.001) on day 9 and in serum (50%, p<0.05) on day 6. However, in the brain, Hg increased by 52% (p<0.05) on day 6. Hg went unchanged in the liver. An infection-induced increase of Hg in the brain but unchanged level in the liver may be due to the peak of virus replication and an associated infection-induced expression of MT1. Moreover, the decrease of Hg in serum and the intestine but a concomitant intestinal increase in MT1 on day 6 may reflect a flux and increased retention of Hg to infected organs such as the brain. The pathophysiological interpretation of these preliminary findings requires further research.

Keywords
brain, intestine, liver, serum, virus
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-17563 (URN)10.1016/j.envres.2007.08.002 (DOI)000253618800005 ()17888900 (PubMedID)
Available from: 2008-07-10 Created: 2009-02-06 Last updated: 2017-12-08Bibliographically approved
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