Biomedical subjects

K Møller

Publications and source records attributed to K Møller.

At least 19 recordsLinked to original sources

PubMed2005

Naturally acquired Lawsonia intracellularis infection in pigs studied from weaning to slaughter by indirect immunofluorescence antibody test and polymerase chain reaction on faeces.

The course of naturally acquired Lawsonia intracellularis infection was studied in 41 pigs by testing blood and faeces samples collected four to seven times from before weaning to slaughter 5 months old. At slaughter, a sample of ileum was taken for histopathology. In the first sampling when the pigs were 2-4 weeks old maternally derived IgG against L. intracellularis was demonstrated by immunofluorescence antibody test in nine pigs whereas the bacterium was detected by PCR in faeces from six pigs. The maternally derived antibodies did not prevent pigs from becoming infected as seven pigs later on shed and/or were seropositive for L. intracellularis. The lowest prevalence of L. intracellularis was observed in 6-13 weeks old pigs and it seemed as though L. intracellularis in early infected pigs only activates a minor antibody response. At slaughter 66% of the pigs were found positive by immunofluorescence antibody test compared to 24% by immunohistochemistry on ileal samples. Thus, applied at the time of slaughter the antibody test appeared to be a highly sensitive ante-mortem diagnostic tool for identifying L. intracellularis exposed pigs with or without current proliferative enteropathy.

Aging↗

PubMed2005

Interleukin-6 infusion during human endotoxaemia inhibits in vitro release of the urokinase receptor from peripheral blood mononuclear cells.

Leucocyte expression of the urokinase receptor [urokinase-type plasminogen activator receptor (uPAR)] is regulated by inflammatory mediators. This study investigated the in vivo effect of endotoxin, interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha on uPAR-release in vivo and in vitro in humans. Healthy subjects received intravenous endotoxin injection [high-dose, 2 ng/kg (n=8) and low-dose, 0.06 ng/kg (n=7)], coadministration of 0.06 ng/kg endotoxin and 3 h recombinant human (rh)IL-6 infusion (n=7) or 3 h infusion of rhIL-6 (n=6), rhTNF-alpha (n=6) or NaCl (n=5). Soluble uPAR (suPAR) was measured by enzyme-linked immunosorbent assay in plasma and supernatants from unstimulated and phytohaemagglutinin and lipopolysaccharide-stimulated peripheral blood mononuclear cell (PBMC) cultures incubated for 24 h. The spontaneous and stimulated uPAR-release from PBMC cultures was enhanced 5 h after low-dose endotoxin (both P <0.05), but coadministration of rhIL-6 during low-dose endotoxaemia abolished this enhanced uPAR release. High-dose endotoxin increased plasma suPAR levels (P <0.001) whereas low-dose endotoxin, rhIL-6 or TNF-alpha did not influence uPAR release in vivo to such degree that a systemic effect on the plasma suPAR level was detectable. Even subclinical doses of endotoxin in vivo enhance the capacity of PBMC to release uPAR after incubation in vitro. The inhibitory effect of IL-6 on endotoxin-mediated uPAR-release in vitro suggests that IL-6 has anti-inflammatory effects on endotoxin-mediated inflammation.

Adult↗

PubMed2005

Effect of carbohydrate ingestion on brain exchange of amino acids during sustained exercise in human subjects.

AIM: This study investigated the effect of prolonged exercise with and without carbohydrate intake on the brain exchange of amino acids, especially focussing on tryptophan and branched-chain amino acids (BCAA). METHODS: Five male subjects exercised for 3 h on a cycle ergometer at 200 +/- 7 W on two occasions; either supplemented with a 6% carbohydrate solution or with flavoured water (placebo). Catheters were inserted into the right internal jugular vein and the radial artery of the non-dominant arm. The brain exchange of amino acids during exercise was calculated from the arterial-jugular venous concentration difference multiplied by plasma flow. RESULTS: About 106 micromol (22 mg) of tryptophan was taken up by the brain during exercise in the placebo trial, whereas no significant uptake was observed in the carbohydrate trial. In accordance, the arterial concentration of free tryptophan increased from 12 +/- 1 to 20 +/- 2 micromol L(-1) during the placebo trial and was significantly higher compared with the glucose trial (14 +/- 1 micromol L(-1) at the end of exercise). Also, the arterial concentration of total tryptophan (free and albumin-bound) increased during the first 30 min of exercise in both trials, but returned to the basal level at 180 min of exercise. In both trials, BCAA were taken up by the brain while glutamine was released. CONCLUSION: The present data show that both tryptophan and BCAA are taken up by the brain during prolonged exercise, and we suggest that the cerebral uptake of tryptophan may relate to increased synthesis of serotonin (5-HT) in the brain.

Adult↗

PubMed2005

Circulating YKL-40 levels during human endotoxaemia.

YKL-40 is secreted by macrophages and neutrophils and patients with bacterial infections have elevated circulating YKL-40. The aim was to evaluate changes in plasma YKL-40 (determined by enzyme-linked immunosorbent assay (ELISA) at 0, 2, 4, 8, 24 and 32 h) in eight healthy volunteers after injection with Esherichia coli endotoxin or saline. Plasma YKL-40 increased after endotoxin injection from 31 microg/l (range 19-39 microg/l) to a maximum of 159 microg/l (61-552 microg/l, P < 0.01) at 24 h. The finding that plasma YKL-40 increased after endotoxin injection compared with saline (P < 0.001) suggests that YKL-40 has a functional role in infections.

Adipokines↗

PubMed2004

Infection dynamics of Lawsonia intracellularis in pig herds.

Little information is known about the natural course and within-herd prevalence of porcine proliferative enteropathy caused by Lawsonia intracellularis. The objective of the study was to investigate the within-herd dynamics of naturally acquired L. intracellularis infection in pigs from weaning to slaughter. The study was designed as a longitudinal survey where 100 pigs from five herds were randomly selected at weaning (approximately 4 weeks of age). Every second week until slaughter (10-12 times, i.e. 20-24 weeks) the pigs were weighed and faecal as well as blood samples were collected. Faecal shedding of L. intracellularis was assessed by real time-PCR and sero-conversion by an indirect immunofluorescence antibody test (IFAT). Clinical disease was not reported but infection was present in all herds and the PCR assay indicated infection in 75% of pigs examined. Most L. intracellularis infected pigs were shedding at 10-12 weeks of age (22-29 kg) and shed for 2-6 successive weeks. After 18 weeks of age all shedding had ceased and re-infection at PCR detectable level was not seen. Variable L. intracellularis associated impact on growth rate was observed. Immediately before bacterial shedding and during early infection the average growth rate declined whereas a compensatory impact was observed during later infection and after bacterial shedding had ceased. The performance of the IFAT resembled the bacteriological test almost perfectly. Sero-conversion was first detected at 12-14 weeks of age. Relative to the bacterial shedding, the onset of sero-conversion was a little delayed, in general, most pigs had sero-converted 2 weeks after the first shedding. Once sero-converted, 92% of the pigs remained sero-positive over the entire survey period.

Animals↗

PubMed2004

Horizontal gene transfer promoted evolution of the ability to propagate under anaerobic conditions in yeasts.

The ability to propagate under anaerobic conditions is an essential and unique trait of brewer's or baker's yeast ( Saccharomyces cervisiae). To understand the evolution of facultative anaerobiosis we studied the dependence of de novo pyrimidine biosynthesis, more precisely the fourth enzymic activity catalysed by dihydroorotate dehydrogenase (DHODase), on the enzymes of the respiratory chain in several yeast species. While the majority of yeasts possess a mitochondrial DHODase, Saccharomyces cerevisiae has a cytoplasmatic enzyme, whose activity is independent of the presence of oxygen. From the phylogenetic point of view, this enzyme is closely related to a bacterial DHODase from Lactococcus lactis. Here we show that S. kluyveri, which separated from the S. cerevisiae lineage more than 100 million years ago, represents an evolutionary intermediate, having both cytoplasmic and mitochondrial DHODases. We show that these two S. kluyveri enzymes, and their coding genes, differ in their dependence on the presence of oxygen. Only the cytoplasmic DHODase promotes growth in the absence of oxygen. Apparently a Saccharomyces yeast progenitor which had a eukaryotic-like mitochondrial DHODase acquired a bacterial gene for DHODase, which subsequently allowed cell growth gradually to become independent of oxygen.

Anaerobiosis↗

PubMed2004

Influence of diet on the experimental infection of pigs with Brachyspira pilosicoli.

The effects of five different diets on the experimental infection of pigs with a Danish field isolate of Brachyspira pilosicoli were investigated. The diets tested were a pelleted and a non-pelleted standard diet based on wheat and barley, the standard diet supplemented with 2 per cent lactic acid, a fermented liquid feed and a diet based on cooked rice. Two trials were conducted, each with six groups of six pigs; in each, two of the groups were fed the standard diet. One of these groups and the other four groups were challenged after two weeks on the diets and euthanased four weeks later. The clinical signs of B pilosicoli infection varied from loose stools to watery, mucoid diarrhoea. The group fed the rice diet excreted B pilosicoli in their faeces for a significantly shorter period than the group fed the standard diet (P < 0.01), and fewer of them excreted the organism (P < 0.05). All the pigs fed the pelleted diet excreted B pilosicoli in their faeces, and significantly more of them showed clinical signs of disease than the pigs fed the standard diet (P < 0.05). The fermented liquid feed and the diet containing lactic acid had no significant effect on the excretion of B pilosicoli or on the numbers of pigs showing clinical signs of disease.

Animals↗

PubMed2004

Exercise induces the release of heat shock protein 72 from the human brain in vivo.

The present study tested the hypothesis that in response to physical stress the human brain has the capacity to release heat shock protein 72 (Hsp72) in vivo. Therefore, 6 humans (males) cycled for 180 minutes at 60% of their maximal oxygen uptake, and the cerebral Hsp72 response was determined on the basis of the internal jugular venous to arterial difference and global cerebral blood flow. At rest, there was a net balance of Hsp72 across the brain, but after 180 minutes of exercise, we were able to detect the release of Hsp72 from the brain (335 +/- 182 ng/min). However, large individual differences were observed as 3 of the 6 subjects had a marked increase in the release of Hsp72, whereas exercise had little effect on the cerebral Hsp72 balance in the remaining 3 subjects. Given that cerebral blood flow was unchanged during exercise compared with values obtained at rest, it is unlikely that the cerebral Hsp72 release relates to necrosis of specific cells within the brain. These data demonstrate that the human brain is able to release Hsp72 in vivo in response to a physical stressor such as exercise. Further study is required to determine the biological significance of these observations.

Adult↗

PubMed2003

Pyruvate decarboxylases from the petite-negative yeast Saccharomyces kluyveri.

Saccharomyces kluyveri is a petite-negative yeast, which is less prone to form ethanol under aerobic conditions than is S. cerevisiae. The first reaction on the route from pyruvate to ethanol is catalysed by pyruvate decarboxylase, and the differences observed between S. kluyveri and S. cerevisiae with respect to ethanol formation under aerobic conditions could be caused by differences in the regulation of this enzyme activity. We have identified and cloned three genes encoding functional pyruvate decarboxylase enzymes (PDCgenes) from the type strain of S. kluyveri (Sk- PDC11, Sk- PDC12 and Sk- PDC13). The regulation of pyruvate decarboxylase in S. kluyveri was studied by measuring the total level of Sk- PDC mRNA and the overall enzyme activity under various growth conditions. It was found that the level of Sk- PDC mRNA was enhanced by glucose and oxygen limitation, and that the level of enzyme activity was controlled by variations in the amount of mRNA. The mRNA level and the pyruvate decarboxylase activity responded to anaerobiosis and growth on different carbon sources in essentially the same fashion as in S. cerevisiae. This indicates that the difference in ethanol formation between these two yeasts is not due to differences in the regulation of pyruvate decarboxylase(s), but rather to differences in the regulation of the TCA cycle and the respiratory machinery. However, the PDC genes of Saccharomyces/ Kluyveromyces yeasts differ in their genetic organization and phylogenetic origin. While S. cerevisiae and S. kluyveri each have three PDC genes, these have apparently arisen by independent duplications and specializations in each of the two yeast lineages.

Aerobiosis↗

PubMed2003

Association between fatigue and failure to preserve cerebral energy turnover during prolonged exercise.

AIM: This study evaluated if the fatigue and apathy arising during exercise with hypoglycaemia could relate to a lowering of the cerebral metabolic rates of glucose and oxygen. METHODS AND RESULTS: Six males completed 3 h of cycling with or without glucose supplementation in random order. Cerebral blood flow, metabolism and interleukin-6 (IL-6) release were evaluated with the Kety-Schmidt technique. Blood glucose was maintained during the glucose trial, while it decreased from 5.2 +/- 0.1 to 2.9 +/- 0.3 mmol L-1 (mean +/- SE) after 180 min of exercise in the placebo trial with a concomitant increase in perceived exertion (P < 0.05). During hypoglycaemia, the cerebral glucose uptake was reduced from 0.34 +/- 0.05 to 0.28 +/- 0.04 micromol g(-1) min(-1), while the cerebral uptake of beta-hydroxybutyrate increased to 5 +/- 1 pmol g(-1) min(-1) (P < 0.05). The reduced glucose uptake was accompanied by a lowering of the cerebral metabolic rate of oxygen from 1.84 +/- 0.19 mmol g(-1) min(-)1 during exercise with glucose supplementation to 1.60 +/- 0.16 mmol g(-1) min(-1) during hypoglycaemia (P < 0.05). In addition, the cerebral IL-6 release was reduced from 0.4 +/- 0.1 to 0.0 +/- 0.1 pg g(-1) min(-1) (P < 0.05). CONCLUSIONS: Exercise-induced hypoglycaemia limits the cerebral uptake of glucose, exacerbates exercise, reduces the cerebral metabolic rate of oxygen and attenuates the release of IL-6 from the brain.

3-Hydroxybutyric Acid↗

PubMed2003

Circulating adiponectin levels during human endotoxaemia.

Adiponectin, an adipocytokine secreted by fat tissue, may prevent development of diabetes type II, as high adiponectin levels are linked with insulin sensitivity. In contrast, tumour necrosis factor (TNF)-alpha, which is also produced by fat tissue, leads to insulin resistance and furthermore inhibits adiponectin mRNA production and secretion of the protein. However, adiponectin also negatively regulates TNF-alpha levels. Therefore, we set out to test whether an infusion of endotoxin would influence circulating adiponectin levels in healthy human subjects. Twenty-three healthy human subjects were injected with endotoxin (2 ng/kg body weight); eight of these subjects were also injected with saline and served as controls. Plasma levels of adiponectin, TNF-alpha and interleukin-6 were measured at 0, 1.5, 2, 4, 8 and 24 h. TNF-alpha and interleukin-6 levels peaked at 1.5 h and 2 h, respectively. Control subjects injected with saline showed a decrease in adiponectin plasma levels with time (P < 0.05) presumably owing to the effect of fasting or physical inactivity. However, there was no change in adiponectin plasma levels in endotoxin injected subjects, thus the effect of fasting was opposed. In conclusion, circulating adiponectin levels are reduced during a resting and fasting state, an effect reversed by endotoxin injection.

Adiponectin↗

PubMed2002

Cerebral blood flow, oxidative metabolism and cerebrovascular carbon dioxide reactivity in patients with acute bacterial meningitis.

BACKGROUND: The optimal arterial carbon dioxide tension (P(a)CO(2)) in patients with acute bacterial meningitis (ABM) is unknown and controversial. The objective of this study was to measure global cerebral blood flow (CBF), cerebrovascular CO(2) reactivity (CO(2)R), and cerebral metabolic rates (CMR) of oxygen (O(2)), glucose (glu), and lactate (lac), in patients with ABM and compare the results to those obtained in healthy volunteers. METHODS: We studied 19 patients (17 of whom were sedated) with ABM and eight healthy volunteers (controls). CBF was measured during baseline ventilation and hyperventilation with single-photon emission computed tomography (SPECT) (14 patients) and/or the Kety-Schmidt technique (KS) (11 patients and all controls). In KS studies, CMR was measured by multiplying the arterial to jugular venous concentration difference (a-v D) by CBF. RESULTS: CBF did not differ significantly among groups, although a larger variation was seen in patients than in controls. CO(2)R was not significantly different among groups. At baseline, patients had significantly lower a-v DO(2), CMR(O(2)), CMR(glu), and CMR(lac) than controls. CMR(O(2)) did not change between hyperventilation compared to baseline ventilation, whereas CMR(glu) increased. CONCLUSION: In patients with acute bacterial meningitis, we found variable levels of CBF and cerebrovascular CO(2) reactivity, a low a-v DO(2), low cerebral metabolic rates of oxygen and glucose, and a cerebral lactate efflux. In these patients, a ventilation strategy guided by jugular bulb oximetry and/or repeated CBF measurements may be more optimal in terms of cerebral oxygenation than a strategy aiming at identical levels of P(a)CO(2) for all patients.

Adult↗

PubMed2002

Effects of finasteride on vascular endothelial growth factor.

OBJECTIVE: Finasteride has been shown to reduce prostate bleeding in patients with benign prostatic hyperplasia (BPH). The mechanisms behind this are not known, but it has been suggested that finasteride reduces bleeding by inhibiting angiogenesis in the prostate. Studies in animals have shown that castration rapidly induces involution of the prostate vasculature, and androgen-stimulated prostate growth may be angiogenesis dependent. The objective of this study was to explore the response to finasteride on the vasculature and the expression of vascular endothelial growth factor (VEGF), a potent regulatory factor of angiogenesis in human prostate tissue. MATERIAL AND METHODS: Patients with BPH were randomly assigned to 3 months of treatment either with finasteride (5 mg/day) or placebo before undergoing transurethral resection of the prostate (TURP). Prostate tissue VEGF expression was quantified by Western blot and the vascular density determined in Factor VIII immunostained tissue sections. Serum concentrations of VEGF were measured with ELISA technique. RESULTS: Patients treated with finasteride (n = 15) showed a decrease in prostate tissue VEGF(165) expression compared with placebo (n = 13) treated patients (p < 0.05), but the vascular density and the serum VEGF levels were unaffected. CONCLUSIONS: This study shows that finasteride treatment decreases VEGF expression in the human prostate.

5-alpha Reductase Inhibitors↗

PubMed2002

Activated T lymphocytes disappear from circulation during endotoxemia in humans.

Seventeen volunteers received an intravenous bolus of endotoxin (2 ng/kg of body weight). Endotoxin-induced lymphopenia was constituted mainly by cells with an immature phenotype (CD45RA(+) CD45RO(-)) that were less likely to undergo apoptosis (CD28(+)), whereas cells with the highest rates of disappearance were characterized by an activated phenotype (CD45RA(-) CD45RO(+)) as well as a phenotype linked to apoptosis (CD95(+) CD28(-)). In conclusion, endotoxin-induced lymphopenia reflects the disappearance from the circulation of activated lymphocytes prone to undergo apoptosis.

Adult↗

PubMed2002

Application of a 5' nuclease assay for detection of Lawsonia intracellularis in fecal samples from pigs.

A 5' nuclease assay was developed to detect Lawsonia intracellularis in porcine fecal samples. The specific probe and primers were chosen by using the 16S ribosomal DNA gene as a target. The 5' nuclease assay was used with a total of 204 clinical samples, and the results were compared to those of immunohistochemistry (IM) on ileal sections of the same animals. There was 91% agreement between the results of IM and the 5' nuclease assay. In the 5' nuclease assay, 111 (54%) of the pigs tested positive for L. intracellularis infection, with a mean cycle threshold (Ct) value of 27.2, whereas 98 (48%) of the pigs tested positive by IM. On average, the Ct and DeltaRn values for the positive samples were 27.2 (standard deviation [SD], 3.7) and 1.6 (SD, 0.7), respectively. A Ct value of 27.2 corresponds to a fecal excretion of approximately 10(7) L. intracellularis cells per g of feces. Furthermore, a total of 40 fecal samples derived from a herd known to be free from infection with L. intracellularis all tested negative, with a Ct value of 40. By using a Ct value of 36 as the cutoff limit, the detection limit of the assay was 1 L. intracellularis cell per PCR tube. In conclusion, the 5' nuclease assay that has been developed represents an applicable fast method for detection of L. intracellularis in fecal samples, with a sensitivity and specificity comparable to those of IM.

Animals↗

PubMed2001

[Is polysaccharide pneumococcal vaccine effective in adults?].

Pneumococcal (PC) infections are common and dangerous. Polysaccharide PC vaccine is recommended in some countries for use in adults who have an increased risk of PC infection. Randomised studies of the clinical effect of polysaccharide PC vaccine in healthy adults reported a protective effect, which, in general, was not reproduced in subsequent studies of risk groups. Case-control studies showed a protective effect, but were potentially biased. Two meta-analyses found that the vaccine had an effect on the incidence of PC bacteraemia and pneumonia in healthy adults, but had no effect in risk groups; one meta-analysis found no evidence of less effect in risk groups. There is insufficient evidence to support mass vaccination of risk groups, including elderly people, with polysaccharide PC vaccine.

Adult↗

PubMed2001

[Sample size and number needed to treat--a statistical case study].

The sample size necessary in each group to detect a significant effect of a vaccine on a given disease in a randomised clinical trial (RCT) can be calculated from the observed disease incidence without vaccine, the expected incidence with vaccine, and the desired level of significance and statistical power of the study. In this example, sample size is calculated for an RCT of the effect of pneumococcal vaccine on the incidence of pneumococcal sepsis. The number of persons needed to be vaccinated to prevent one episode of pneumococcal sepsis can be similarly calculated from the observed incidences with and without vaccine.

Humans↗

PubMed2001

Risk factors for intestinal pathogens in Danish finishing pig herds.

The objective of this investigation was to identify risk factors for infection with the intestinal bacteria: Lawsonia intracellularis, Brachyspira hyodysenteriae, Serpulina intermedia, Brachyspira innocens, Brachyspira pilosicoli and swine-pathogenic Escherichia coli (serogroups O138, O139, O141 and O149) in Danish finishing pig herds.A total of 79 herds was randomly selected and visited during 1998. From each herd, 20 faecal samples were collected from individual pigs weighing 30-50 kg. In total, 1580 faecal samples were collected and examined by polymerase chain reaction (L. intracellularis) or culture (all other agents). Information on feed and management procedures was collected by filling in questionnaires at the herd visits. The questionnaires included information on 29 dichotomous variables and three continuous variables. Variables with P<0.25 in a preliminary screening (chi2- or t-test) were selected for the statistical modelling. Our conclusions, based on the results of multifactorial logistic regression (cut-off: P=0.05), were the following: 1. Consistent batch production was associated with reduced prevalences of L. intracellularis and weakly -haemolytic spirochetes (S. intermedia, B. innocens, B. pilosicoli) (OR's=0.43 and 0.06, respectively). 2. Home-mixed (and/or non-pelleted) feed was associated with reduced prevalences of L. intracellularis and weakly -haemolytic spirochetes (OR's=0.6 and 0.4, respectively). 3. Providing straw to finishers was associated with a reduced prevalence of weakly -haemolytic spirochetes (OR=0.28-0.32). 4. Not using antimicrobial growth promoters for piglets was associated with an increased prevalence of S. intermedia (OR=11.11). 5. Rare occurrence of post-weaning diarrhoea (as opposed to common) was associated with an increased prevalence of weakly -haemolytic spirochetes (OR=8.3-13.7).

Animals↗