Peter M H Heegaard

Technical University of Denmark, Lyngby, Capital Region, Denmark

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Publications (105)283.24 Total impact

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    ABSTRACT: The IPEC-J2 cell line was studied as a simple model for investigating responses of the newborn intestinal epithelium to diets. Especially, the small intestine of immature newborns is sensitive to diet-induced inflammation. We investigated gene expression of epithelial- and immune response-related genes in IPEC-J2 cells stimulated for 2 h with milk formula (CELL-FORM), colostrum (CELL-COLOS), or growth medium (CELL-CONTR) and in distal small intestinal tissue samples from preterm pigs fed milk formula (PIG-FORM) or colostrum (PIG-COLOS). High throughput quantitative PCR analysis of 48 genes revealed the expression of 22 genes in IPEC-J2 cells and 31 genes in intestinal samples. Principal component analysis (PCA) discriminated the gene expression profile of IPEC-J2 cells from that of intestinal samples. The expression profile of intestinal tissue was separated by PCA into 2 groups according to diet, whereas no diet-dependent grouping was seen for IPEC-J2 cells. Expression differences between PIG-FORM and PIG-COLOS were found for DEFB1, CXCL10, IL1RN, and ALPI, while IL8 was upregulated in CELL-FORM compared with CELL-CONTR. These differences, between IPEC-J2 cells and intestinal tissue from preterm pigs, both used as models for the newborn intestine, underline that caution must be exercised prior to analysis and interpretation of diet-induced effects on gene expression.
    04/2013; 2013(4). DOI:10.1155/2013/980651
  • K L Proudfoot · M B Jensen · P M H Heegaard · M A G von Keyserlingk ·
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    ABSTRACT: Cows are often moved from a group to an individual maternity pen just before calving. However, it is unclear whether moving cows during labor may alter their behavior or affect the progress of labor. The aim of this study was to determine if moving cows to a maternity pen at different stages of labor would influence calving behavior or the length of the second stage of labor. Seventy-nine multiparous Holstein dairy cows were moved from 1 of 2 group pens to 1 of 10 maternity pens adjacent to each group pen either 3 d before expected calving date or when one or more behavioral or physical signs of labor were observed. These signs were noted, and were used to retrospectively categorize cows into 1 of 3 movement categories: (1) moved before labor, (2) moved during early stage I labor (signs of suddenly tense and enlarged udder, raised tail or relaxed pelvic ligaments; could also be immediately prelabor), or (3) moved during late stage I labor (signs of viscous, bloody mucus or abdominal contractions; could also be transitioning to stage II labor). Calves were weighed within 12 h of birth and remained with their dam for 3 d. The length of the second stage of labor (the time between first abdominal contractions to the delivery the calf) and the total time of abdominal contractions, lying time, and number of position changes from standing to lying made by the cow in the hour before calving were recorded. A single blood sample was taken from the jugular vein of cows 3 to 27 h after calving to determine content of haptoglobin, a marker of systemic inflammation. The effect of movement category on length of the second stage of labor and behavioral variables was tested with ANOVA; category was a fixed effect and calf body weight (BW) and cow parity were covariates. The relationship between haptoglobin and the length of the second stage of labor was tested in a model with time of sampling relative to calving as a covariate. Cows moved during late stage I had the longest labor, but did not have longer contractions compared with cows in the other categories. These same cows spent half as much time lying in the 1 h before calving compared with cows in the other categories, but did not differ in the number of position changes from standing to lying. We did not have the power to test the effect of movement category on haptoglobin, but cows with longer stage II labor had higher haptoglobin postcalving. Moving cows to a maternity pen during the late part of the first stage of labor caused a delay in the second stage of labor, and this was likely driven by altered lying behavior.
    Journal of Dairy Science 01/2013; 96(3). DOI:10.3168/jds.2012-6000 · 2.57 Impact Factor
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    ABSTRACT: The acute phase protein orosomucoid (ORM) has anti-inflammatory and immunomodulatory effects, and may play an important role in the maintenance of metabolic homeostasis in obesity-induced low-grade inflammation. Even though the pig is a widely used model for obesity related metabolic symptoms, the expression of ORM has not yet been characterized in such pig models. The objective of this study was to investigate the expression of ORM1 mRNA in liver, visceral adipose tissue, subcutaneous adipose tissue (SAT) from the abdomen or retroperitoneal abdominal adipose tissue (RPAT) and SAT from the neck, as well as the serum concentration of ORM protein in three porcine obesity models; the domestic pig, Göttingen minipigs and Ossabaw minipigs. No changes in ORM1 mRNA expression were observed in obese pigs compared to lean pigs in the four types of tissues. However, obese Ossabaw minipigs, but none of the other breeds, showed significantly elevated ORM serum concentrations compared to their lean counterparts. Studies in humans have shown that the expression of ORM was unchanged in adipose tissue depots in obese humans with an increased serum concentration of ORM. Thus in this respect, obese Ossabaw minipigs behave more similarly to obese humans than the other two pig breeds investigated.
    Veterinary Immunology and Immunopathology 11/2012; 151(3). DOI:10.1016/j.vetimm.2012.11.002 · 1.54 Impact Factor
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    ABSTRACT: The human sequential organ failure assessment (SOFA) scoring system is used worldwide in intensive care units for assessing the extent of organ dysfunction/failure in patients with severe sepsis. An increasing number of septic cases are caused by Gram-positive bacteria as Staphylococcus aureus. The aim of the current study was to apply the human SOFA parameters in an awake, porcine model of severe S. aureus sepsis. Five pigs were inoculated intravenously with S. aureus and two control animals were sham-inoculated. Extensive clinical monitoring and sequential blood sampling was obtained and analysed for SOFA parameters. Dysfunction/failure was observed in the respiratory, haemostatic and hepatic system of all infected animals, together with initial cardiovascular dysfunction. The pulmonary system was the first to fail clinically, which corresponds with similar human findings, whereas the liver was affected earlier in pigs compared to humans. The use of human SOFA parameters was valuable in identifying dysfunctional/failing organs and showed consistency between this porcine model and human severe sepsis. Applying SOFA parameters in this model increased the relevance for comparison to clinical methods of evaluating human severe sepsis. Changes in SOFA parameters may in future porcine studies serve as a target for monitoring the effect of therapeutic intervention.
    Apmis 11/2012; 120(11):909-21. DOI:10.1111/j.1600-0463.2012.02917.x · 2.04 Impact Factor
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    Tina Rødgaard · Kerstin Skovgaard · Jan Stagsted · Peter M H Heegaard ·
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    ABSTRACT: Abstract The pig has been proposed as a relevant model for human obesity-induced inflammation, and cloning may improve the applicability of this model. We tested the assumptions that cloning would reduce interindividual variation in gene expression of innate immune factors and that their expression would remain unaffected by the cloning process. We investigated the expression of 40 innate immune factors by high-throughput quantitative real-time PCR in samples from liver, abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and neck SAT in cloned pigs compared to normal outbred pigs. The variation in gene expression was found to be similar for the two groups, and the expression of a small number of genes was significantly affected by cloning. In the VAT and abdominal SAT, six out of seven significantly differentially expressed genes were downregulated in the clones. In contrast, most differently expressed genes in both liver and neck SAT were upregulated (seven out of eight). Remarkably, acute phase proteins (APPs) dominated the upregulated genes in the liver, whereas APP expression was either unchanged or downregulated in abdominal SAT and VAT. The general conclusion from this work is that cloning leads to subtle changes in specific subsets of innate immune genes. Such changes, even if minor, may have phenotypic effects over time, e.g., in models of long-term inflammation related to obesity.
    08/2012; 14(5):407-17. DOI:10.1089/cell.2012.0026
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    ABSTRACT: The single nucleotide polymorphism (SNP) G949T in the mannose-binding lectin ( MBL ) 1 gene has been associated with low MBL-A concentration in serum and detected at different frequencies in various European pig populations. However, the origin of this SNP is not known. Part of the MBL1 gene was sequenced in 12 wild boar/Large White crossbred pigs from the second backcross (BC (2) ) generation in a family material originating from two wild boar x Large White intercrosses. Also, MBL-A serum concentration was measured in the entire BC (2) generation (n = 45). Furthermore, the genotypes of 68 wild boars from Sweden, Austria, the Czech Republic, and Japan were determined in regard to five previously described SNPs in MBL1 . The T allele of G949T was present among the BC (2) animals. MBL-A serum concentration in the BC (2) animals showed a bimodal distribution, with one-third of the animals at levels between 0.7 and 1.6 μg mL(-1) and the remaining pigs at levels around 13 μg mL(-1) . There was a co-variation between the presence of the T allele and low MBL-A concentration in serum. The genotyping of the wild boars revealed differences between populations. The T allele of G949T was not detected in the Austrian and Japanese samples and is thus unlikely to be an original feature of wild boars. In contrast, it was present at high frequency (0.35) among the Swedish wild boars, probably representing a founder effect. Five MBL1 haplotypes were resolved. Only two of these were present among the Japanese wild boars compared to four in each of the European populations. This difference may reflect differences in selection pressure and population history.
    International Journal of Immunogenetics 06/2012; 40(2). DOI:10.1111/j.1744-313X.2012.01132.x · 1.25 Impact Factor
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    ABSTRACT: Acute respiratory distress syndrome is a common complication in severe sepsis. In pigs, the lungs play an important role in clearing systemic bacterial infections due to pulmonary intravascular macrophages found specifically in pigs. However, this increases the exposure of the porcine lungs to pathogens and potential injury. The authors propose that increasing the concentration of the inoculum without changing the bacterial dose will lead to severe sepsis with pronounced pulmonary lesions. This could potentially create a risk of cytokine spillover to the circulation, leading to an increased systemic response. Eight Danish Landrace pigs, approximately 10 weeks old, were inoculated twice with a low or once with a high concentration of Staphylococcus aureus. Three pigs were sham-inoculated. The animals were grouped based on macro- and microscopic lung lesions. The mRNA expression of local pulmonary inflammatory markers was compared to protein levels of systemic inflammatory markers. The most severe pulmonary lesions were observed in animals receiving the high S. aureus concentration, indicating that severity of lesions is dependent on inoculum concentration rather than total numbers of bacteria. Furthermore, local mRNA expression of inflammatory cytokines appeared to be dependent on the magnitude and severity of tissue destruction, including the ability to confine the lesions. Increasing mRNA levels of serum amyloid A could be a confident marker of severity of pulmonary lesions. Since no correlation was observed between local and systemic levels of inflammatory cytokines, this finding could indicate an ability of the porcine lung to compartmentalize the local inflammatory response and thus restrict systemic contribution.
    Veterinary Pathology 03/2012; 49(6). DOI:10.1177/0300985812439726 · 1.87 Impact Factor
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    ABSTRACT: It is suggested that cyclooxygenase 2 (COX-2) derived prostaglandins contributes to the progressive bone loss seen in osteomyelitis lesions. In the present study we examined the expression of COX-2 in bones from 23 pigs with experimental osteomyelitis. Osteomyelitis was induced with Staphylococcus aureus and groups of animals were euthanized following 6 h, 12 h, 24 h, 2 days, 5 days, 11 days and 15 days, respectively. Expression of COX-2 was evaluated immunohistochemically and combined with characterization of morphological changes in bone tissue. Furthermore, the serum concentrations of alkaline phosphatase and haptoglobin were measured. Extensive COX-2 expression by osteoblasts was present 2 days after inoculation together with many activated osteoclasts. Simultaneously, the serum concentration of alkaline phosphatase decreased whereas the haptoglobin concentration increased. This is the first in vivo study showing an early wave of COX-2 mediated bone resorption during osteomyelitis. Therefore, treatment aiming to reduce the break down of bone tissue directed by the COX-2 pathway might be suggested early in the course of the disease.
    Prostaglandins & other lipid mediators 01/2012; 97(3-4):103-8. DOI:10.1016/j.prostaglandins.2012.01.002 · 2.38 Impact Factor
  • Nanna S Sorensen · Ulrik Boas · Peter M H Heegaard ·
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    ABSTRACT: Peptidoglycan is a widespread bacterial PAMP molecule and a powerful initiator of innate immune responses. It consists of repeating units of MDP, which as a monomer is only weakly immunostimulatory. Here, MDP-coupled dendrimers were prepared and investigated for stimulation of pig blood mononuclear cells. Compared to monomeric MDP, MDP-dendrimers induced a markedly enhanced production of IL-12 p40, IL-1β and IL-6 and completely down-regulated surface expression of B7 and MHC class II. These results suggest a possible novel strategy based on controlled multimerization of minimal PAMP motifs on dendrimers for preparing molecularly defined immunostimulators with predictable bioactivities.
    Macromolecular Bioscience 08/2011; 11(11):1484-90. DOI:10.1002/mabi.201100105 · 3.85 Impact Factor
  • C Stenfeldt · P.M.H. Heegaard · A Stockmarr · G.J. Belsham ·
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    ABSTRACT: A novel technique of endoscopical collection of small tissue samples was used to obtain sequential tissue samples from the dorsal soft palate (DSP) of individual cattle infected with foot-and-mouth disease virus (FMDV) at different phases of the infection. Levels of mRNA encoding interferon (IFN)-α and IFN-β as well as tumour necrosis factor (TNF)-α were measured in these samples by quantitative reverse transcriptase polymerase chain reaction. Expression of IFN-β mRNA was significantly down-regulated in the biopsy samples harvested during the acute phase of infection, while there was no statistically significant effect on the expression of IFN-α mRNA compared with baseline levels. In contrast, the mRNA encoding TNF-α was significantly up-regulated in samples collected during both acute and late (>28 days post infection) phases of infection. There were also significantly higher levels of TNF-α mRNA expressed in samples derived from animals that were identified subsequently as persistently infected FMDV-carriers. It was concluded that there was a significant difference in the host-response in the DSP of calves that were identified as persistently infected, subclinical carriers of FMDV.
    Journal of comparative pathology 08/2011; 146(2-3):243-52. DOI:10.1016/j.jcpa.2011.06.005 · 1.14 Impact Factor
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    ABSTRACT: Mannose-binding lectin (MBL) is a collagenous lectin that kills a wide range of pathogenic microbes through complement activation. The MBL1 and MBL2 genes encode MBL-A and MBL-C, respectively. MBL deficiency in humans is associated with higher susceptibility to viral as well as bacterial infections. A number of single nucleotide polymorphisms (SNP) have been identified in the collagen-like domain of the human MBL gene, of which several are strongly associated with decreased concentrations of MBL in serum. In this study, we have identified a number of SNPs in the porcine MBL-A gene. Sequence comparisons identified a total of 14 SNPs, eight of which were found in exons and six in introns. Four of the eight exon-located SNPs were non-synonymous. Sequence data from several Duroc and Landrace pigs identified four different haplotypes. One haplotype was found in Duroc pigs only, and three haplotypes were found in the Landrace pigs. One of the identified haplotypes was associated with low concentration of MBL-A in serum. The concentration of MBL-A in serum was further assessed in a large number of Duroc and Landrace boars to address its correlation with disease frequency. The MBL-A concentration in Duroc boars showed one single population, whereas Landrace boars showed four distinct populations for MBL-A concentration. The Landrace boars were finally assessed for disease incidence, and the association with the concentration of MBL-A in serum was investigated. No association between MBL and disease incidence was found in this study.
    Immunogenetics 05/2011; 63(5):309-17. DOI:10.1007/s00251-011-0512-1 · 2.23 Impact Factor
  • L.K. Isling · B Aalbæk · M.M. Birck · P.M.H. Heegaard · P.S. Leifsson ·
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    ABSTRACT: The initial pathology and pathogenesis of pyelonephritis and the influence of different strains of Escherichia coli were investigated in a novel porcine model. Nine female pigs were divided into three groups (A, B and C) and inoculated repeatedly into one renal pelvis with porcine pyelonephritis E. coli strain LK67 (P fimbriae PapG(I)), LK76 (type 1 fimbriae) or LK82 (type 1 fimbriae and P fimbriae PapG(II/III)), respectively. The contralateral kidneys were inoculated with saline and served as controls. Pigs were killed 6h post-inoculation (hpi). Differential leucocyte counts, serum biochemical analyses and measurement of serum concentrations of proinflammatory cytokines and acute phase proteins were carried out at 0, 3 and 6 hpi. Bacteriological evaluation of urine, kidneys, spleen, liver, abdominal swabs and blood samples and gross and histopathological evaluation of kidneys, renal lymph nodes, liver and spleen were performed by quantitative, semiquantitative and/or descriptive methods. Immunohistochemistry was used to identify cells expressing L1 antigen, CD3ɛ, CD4, CD8, CD79αcy and lysozyme, and to identify E. coli and Tamm-Horsfall protein (THP). E. coli was re-isolated from all inoculated kidneys. Gross and microscopical lesions of acute pyelonephritis were demonstrated in all but one kidney inoculated with E. coli, but in none of the control kidneys. Renal parenchymal infiltration with both neutrophils and mononuclear cells, primarily CD3+ T lymphocytes, was observed at 6 hpi. Most T lymphocytes were CD8+. Pigs in group C had the highest mean pathology scores. Neutrophils were the dominant renal leucocyte in this group, while the number of mononuclear cells was at least equal to the number of neutrophils in the lesions of pigs from groups A and B. Kidneys with a high number of E. coli had severe lesions. Systemic spread of E. coli was observed in five pigs. THP was observed interstitially in 89% of the E. coli-inoculated kidneys. In all groups, increased numbers of neutrophils and decreased numbers of lymphocytes and monocytes were shown by differential leucocyte count at 6 hpi, and from 3 to 6 hpi there was a significant increase in C-reactive protein concentration.
    Journal of comparative pathology 05/2011; 144(4):257-68. DOI:10.1016/j.jcpa.2010.10.002 · 1.14 Impact Factor
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    ABSTRACT: Pasteurella multocida is a major cause of porcine pneumonia, but the pathogenesis of the disease is poorly defined. The aim of this study was to further understand the host response to infection by use of a mouse model of P. multocida pneumonia. Twenty female mice were divided into four groups (n=5). Three groups were infected with one of three isolates of P. multocida isolated from clinical cases of chronic porcine pneumonia with necrotizing, suppurative and non-suppurative lesions, respectively. The fourth group served as uninfected controls. Mice were killed 24 h postinfection and samples were collected for bacteriology, histopathology and in-situ hybridization for detection of P. multocida. Measurements of expression of genes encoding matrix metalloproteinase 9 (MMP9) and tissue inhibitor of metalloproteinase 1 (TIMP1) in lung tissue and quantification of serum haptoglobin concentration were performed. P. multocida was found in the lung and spleen. Lung lesions were characterized by deposition of fibrin in alveoli and bronchioles, perivascular oedema, suppuration and necrosis. The cellular infiltration was mainly of neutrophils. Splenic neutrophilic infiltration was also evident. Minor differences in the severity and nature of lesions were seen according to the isolate of P. multocida used for infection. Intranasal infection of mice can therefore be used to evaluate the host response and lesions caused by P. multocida obtained from porcine pneumonic infections. The inflammatory response in this model is associated with increased tissue expression of genes encoding MMP9, TIMP1 and serum haptoglobin concentration.
    Journal of comparative pathology 03/2011; 145(2-3):251-60. DOI:10.1016/j.jcpa.2011.01.002 · 1.14 Impact Factor
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    ABSTRACT: The synergism of infection with conventional cardiovascular risk factors in atherosclerosis is much debated. We hypothesized that coronary arterial injury correlates with infection recurrence and pathogen burden and is further aggravated by hypercholesterolemia. Forty-two Göttingen minipigs were assigned to repeated intratracheal inoculation of PBS, Chlamydia pneumoniae (Cpn), or both Cpn and influenza virus at 8, 11, and 14 wk of age. Animals were fed either standard or 2% cholesterol diet (chol-diet). At 19 wk of age coronary vasomotor responses to acetylcholine (ACh) and adenosine were assessed in vivo and blood and tissue samples were collected. Nonparametric tests were used to compare the groups. In cholesterol-fed animals, total cholesterol/HDL was significantly increased in infected animals compared with noninfected animals [3.13 (2.17-3.38) vs. 2.03 (1.53-2.41), respectively; P = 0.01]. C-reactive protein (CRP) rose in infected animals [10.60 (4.96-18.00) vs. 2.47 (1.44-3.01) μg/ml in noninfected; P < 0.01] without significant difference between the mono- and coinfected groups. Among coinfected animals, both CRP and haptoglobin were lower in those fed chol-diet than in those fed standard diet (P < 0.05). The vasoconstricting response to ACh was most prominent in coinfected animals {769.3 (594-1,129) cm; P = 0.03 vs. noninfected [342 (309-455) cm] and P = 0.07 vs. monoinfected [415 (252.5-971.8) cm]}. Among monoinfected animals, similar to CRP, a trend for less vasoconstriction was observed in those fed chol-diet (P = 0.08). Coinfection of piglets appears to be associated with more pronounced coronary muscarinic vasomotor dysfunction. In monoinfected animals, use of chol-diet seems to dampen both coronary dysfunction and systemic inflammation induced by infection.
    AJP Heart and Circulatory Physiology 02/2011; 300(5):H1595-601. DOI:10.1152/ajpheart.01253.2010 · 3.84 Impact Factor
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    ABSTRACT: Modern adjuvants should induce strong and balanced immune responses, and it is often desirable to induce specific types of immunity. As an example, efficient Th1-immunity-inducing adjuvants are highly in demand. Such adjuvants promote good cell-mediated immunity against subunit vaccines that have low immunogenicity themselves. The development of such adjuvants may take advantage of the increased knowledge of the molecular mechanisms and factors controlling these responses. However, knowledge of such molecular details of immune mechanisms is relatively scarce for species other than humans and laboratory rodents, and in addition, there are special considerations pertaining to the use of adjuvants in veterinary animals, such as production and companion animals. With a focus on veterinary animals, this review highlights a number of approaches being pursued, including cytokines, CpG oligonucleotides, microparticles and liposomes.
    Archives of Virology 02/2011; 156(2):183-202. DOI:10.1007/s00705-010-0863-1 · 2.39 Impact Factor
  • A. M. Danscher · M. B. Thoefner · P. M. H. Heegaard · C. T. Ekstrøm · S. Jacobsen ·
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    ABSTRACT: The aim of the study was to describe the acute phase protein and leukocyte responses in dairy heifers during acute, oligofructose-induced ruminal acidosis. The study included 2 trials involving oral oligofructose overload (17g/kg BW) to nonpregnant Danish Holstein heifers. Trial 1 included 12 heifers all receiving oligofructose, and the experiment consisted of a 3 day control period prior to overload and 9 days surveillance afterwards. Eight heifers were fed grass hay and 4 were fed barley silage. Trial 2 included 10 heifers receiving oligofructose, 4 were euthanized 24h after overload and 6 were euthanized 72h after overload. Six heifers received tap water as control treatment and were euthanized 72 or 96h later. Sampling of blood was performed at 6–48 hour intervals. Samples were analyzed for serum amyloid A (SAA), haptoglobin, and fibrinogen, and total white blood cell counts (WBC) were performed.Heifers receiving oligofructose developed a profound ruminal and systemic acidosis (in Trial 1 and 2 lowest ruminal pH was 4.3±0.2 and 3.8±0.02, respectively, and minimum SBE was −9.3±4.1 and −8.9±2.8, respectively). In Trial 1, SAA concentrations were higher than baseline concentrations on all time points from 6 to 216hours after overload, and heifers fed hay had higher SAA levels (max. 290±151mg/L) than heifers fed silage (max. 225±137mg/L). In Trial 2, SAA concentrations in heifers receiving oligofructose were higher than control heifers at all time points from 12 to 72h after overload (max. 325±149mg/L). In Trial 1, haptoglobin concentrations for hay-fed heifers were higher than baseline concentrations at all time points from 36 to 168h after overload (max. 3449±1702mg/L). Heifers fed silage had lower haptoglobin concentrations than heifers fed hay at 60, 72 and 120h (max. 1802±950mg/L). In Trial 2, haptoglobin concentrations in heifers receiving oligofructose were higher than control heifers at all time points from 18 to 72h after overload (max. 4226±924mg/L). In Trial 1, fibrinogen concentrations did not differ from baseline concentrations at any time points. In Trial 2, fibrinogen concentrations in heifers receiving oligofructose were higher than control heifers at all time points from 36 to 72h after overload (max. 12.2±3.3g/L). In Trial 1, WBC did not differ from baseline concentrations at any time points. In Trial 2, WBC in heifers receiving oligofructose were higher than control heifers at 18 and 24h after overload (max. 13.7±4.3 billions/L). Feeding had no effect on plasma fibrinogen concentrations or WBC in Trial 1.Acute ruminal and systemic acidosis caused by oligofructose overload resulted in distinct acute phase protein and leukocyte responses in dairy heifers. The increased levels of serum acute phase proteins and leukocytes might be a result of ruminitis caused by the ruminal acidosis, of systemic effects of pro-inflammatory molecules translocating across the damaged ruminal epithelium, or a result of the systemic acidosis and accumulation of organic acids. In humans, inflammation has been linked to metabolic diseases. In cattle, studies into the possible links between acid-base changes, inflammation/innate immunity and metabolic disease are warranted as this might improve our understanding of the production disease complexes occurring in particular in the transition period.
    Livestock Science 01/2011; 135(1):62-69. DOI:10.1016/j.livsci.2010.06.009 · 1.17 Impact Factor
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    ABSTRACT: Aortic vascular prosthetic graft infection (AVPGI) with Staphylococcus aureus is a feared post-operative complication. This study was conducted to evaluate the clinical signs and potential biomarkers of infection in a porcine AVPGI model. The biomarkers evaluated were: C-reactive protein (CRP), fibrinogen, white blood cells (WBC), major histocompatibility complex II (MHC II) density, lymphocyte CD4:CD8 ratio and tumour necrosis factor-alpha (TNF-α) in vitro responsiveness. Sixteen pigs were included in the study, and randomly assigned into four groups (n = 4): "SHAM" pigs had their infra-renal aorta exposed by laparotomy; "CLEAN" pigs had an aortic graft inserted; "LOW" and "HIGH" pigs had an aortic graft inserted and, subsequently, S. aureus were inoculated on the graft material (5 × 10(4) colony-forming units [CFU] and 1 × 10(6) CFU, respectively). Biomarkers were evaluated prior to surgery and on day 2, 5, 7, and 14 post-operatively in blood samples. Of all biomarkers evaluated, CRP was superior for diagnosing S. aureus AVPGI in pigs, with a sensitivity of 0.86 and a specificity of 0.75.
    European Journal of Clinical Microbiology 11/2010; 29(11):1453-6. DOI:10.1007/s10096-010-1008-x · 2.67 Impact Factor
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    ABSTRACT: In two separate trials pigs were experimentally infected with Lawsonia intracellularis at 5-6 weeks of age followed by antibiotic treatment and resolution of the primary infection and then re-inoculated at 12-13 weeks of age. A treatment-control group of pigs received the primary infection and antibiotic treatment only, and served as control for the antibiotic treatment of the primary infection. A challenge-control group of pigs received the second inoculation dose only at 12-13 weeks of age to control infectivity of the challenge-dose and susceptibility of pigs to L. intracellularis at this age. Pigs were monitored for shedding of L. intracellularis in faeces by PCR, and for the development of antibodies and responses of acute phase proteins in serum. The presence of L. intracellularis antigen in the intestinal mucosa was examined in post mortem samples by immunohistochemistry.
    Veterinary Microbiology 11/2010; 149(3-4):406-14. DOI:10.1016/j.vetmic.2010.11.028 · 2.51 Impact Factor
  • Nanna S Sorensen · Kerstin Skovgaard · Peter M.H. Heegaard ·
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    ABSTRACT: Pathogen-associated molecular patterns (PAMPs) are conserved molecules of microorganisms inducing innate immune cells to secrete distinct patterns of cytokines. In veterinary species, due to a lack of specific antibodies, cytokines are often monitored as expressed mRNA only. This study investigated the induction of IFN-α, IL-12 p40, IL-1β, TNF-α, IL-6 and IL-10 by PAMP-molecules [CpG oligonucleotide D19 (CpG), peptidoglycan (PGN), lipopolysaccharide (LPS), Pam(3)Cys and poly-U] in porcine blood mononuclear cells (BMC) within a 24 h period. As expected, cytokine responses were PAMP-specific, CpG inducing IFN-α and IL-12 p40, and PGN, LPS and Pam(3)Cys inducing varying amounts of IL-12 p40, IL-1β, TNF-α, IL-6 and IL-10. Surprisingly, the ssRNA-mimic poly-U induced IL-6 and IL-1β only. Using CpG, PGN and LPS, the kinetics of cytokine production measured as mRNA (reverse transcription (RT)-qPCR) and protein (ELISA), respectively, correlated well, mRNA responses preceding protein responses. With the exception of IL-1β and IL-6, mRNA-responses were transient, whereas protein responses, except for TNF-α, followed saturation kinetics. Remarkably, LPS-induced TNF-α mRNA was not followed by a protein response. These results provide guidelines concerning the timing and use of protein and mRNA determinations for the characterization of porcine cytokine responses to PAMPs, although given the low number of animals used here results are preliminary and need confirmation in a larger study.
    Veterinary Immunology and Immunopathology 10/2010; 139(2-4):296-302. DOI:10.1016/j.vetimm.2010.10.016 · 1.54 Impact Factor
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    ABSTRACT: Nine pigs were inoculated intravenously once or twice with 10(8) Staphylococcus aureus per kilogram body weight and sacrificed 12, 24 and 48 h after inoculation. Three sham-infected pigs served as controls. Blood samples were taken for bacteriology, haematology and clinical chemistry. A necropsy was carried out and tissue samples were collected for bacteriology and histology. The onset of clinical disease was seen at 7-8 h after inoculation. The blood bacterial counts remained low throughout the study. All infected pigs developed sepsis characterized by fever, neutrophilia, increased levels of C-reactive protein (CRP) and IL-6, and decreased levels of serum iron. The CRP and IL-6 levels peaked at 36 h, whereas IL-1beta and tumour necrosis factor-alpha showed no obvious changes. Thromboelastography showed increasing hypercoagulability from 12 h and onwards, whereas the platelet numbers declined slightly throughout the experiment. The levels of serum aspartate aminotransferase and bilirubin were elevated at 24 and 36 h. In conclusion, sepsis and severe sepsis were induced as evidenced by dysfunction of the blood clotting system and the liver.
    FEMS Microbiology Letters 08/2010; 309(2):208-16. DOI:10.1111/j.1574-6968.2010.02042.x · 2.12 Impact Factor

Publication Stats

3k Citations
283.24 Total Impact Points


  • 2007-2014
    • Technical University of Denmark
      Lyngby, Capital Region, Denmark
  • 2009-2011
    • National Veterinary Laboratory
      Franklin Lakes, New Jersey, United States
  • 2004-2006
    • Danish Veterinary and Food Administration
      Glostrup, Capital Region, Denmark
  • 2005
    • University of Zaragoza
      • Department of Biochemistry and Molecular and Cellular Biology
      Caesaraugusta, Aragon, Spain