Knut A Eliassen

Norwegian School of Veterinary Science, Kristiania (historical), Oslo, Norway

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Publications (19)42.14 Total impact

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    ABSTRACT: Objective-To compare pharmacokinetics and clearances of creatinine and iohexol as estimates of glomerular filtration rate (GFR) in dogs with various degrees of renal function. Animals-50 Great Anglo-Francais Tricolor Hounds with various degrees of renal function. Procedures-Boluses of iohexol (40 mg/kg) and creatinine (647 mg/kg) were injected IV. Blood samples were collected before administration and 5 and 10 minutes and 1, 2, 4, 6, and 8 hours after administration. Plasma creatinine and iohexol concentrations were assayed via an enzymatic method and high-performance liquid chromatography, respectively. A noncompartmental approach was used for pharmacokinetic analysis. Pharmacokinetic variables were compared via a Bland-Altman plot and an ANOVA. Results-Compared with results for creatinine, iohexol had a significantly higher mean ± SD plasma clearance (3.4 ± 0.8 mL/min/kg vs 3.0 ± 0.7 mL/min/kg) and a significantly lower mean volume of distribution at steady state (250 ± 37 mL/kg vs 539 ± 73 mL/kg), mean residence time (80 ± 31 minutes vs 195 ± 73 minutes), and mean elimination half-life (74 ± 20 minutes vs 173 ± 53 minutes). Despite discrepancies between clearances, especially for high values, the difference was < 0.6 mL/min/kg for 34 (68%) dogs. Three dogs with a low GFR (< 2 mL/min/kg) were classified similarly by both methods. Conclusions and Clinical Relevance-Plasma iohexol and creatinine clearances can be used interchangeably for screening patients suspected of having chronic kidney disease (ie, low GFR), but large differences may exist for dogs with a GFR within or above the reference range.
    No preview · Article · Nov 2012 · American Journal of Veterinary Research
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    ABSTRACT: To compare plasma clearance of inulin and iohexol determined by use of 9 plasma samples for evaluation of glomerular filtration rate in dogs and to evaluate limited-sample approaches for evaluation of plasma clearance of these markers. 43 dogs of various breeds that weighed between 5.5 and 63 kg and that had various degrees of renal function. 9 plasma samples were obtained from each dog at 5 minutes to 6 hours after IV bolus injection of iohexol and inulin. Clearance was calculated by use of results for all 9 samples (ie, reference method). Results for 3 limited-sample strategies for determination of plasma clearance of iohexol and inulin were compared with results for the reference method. Mean clearance of inulin and iohexol for the reference method was 2.72 and 2.48 mL/min/kg, respectively. The mean difference between clearance of these 2 markers for the reference method was 0.24 mL/min/kg. In general, use of the limited-sample strategies yielded clearance values similar to those for the reference method. More accurate estimates of clearance were obtained for iohexol than for inulin by use of the limited-sample methods. Use of iohexol and inulin yielded similar but not identical results for plasma clearance. Accuracy for limited-sample methods would be acceptable for many clinical and research situations.
    No preview · Article · Sep 2010 · American Journal of Veterinary Research
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    ABSTRACT: Glomerular filtration rate (GFR) decreases in the aging human kidney, but limited data exist in dogs. There is an effect of age and body size on estimated GFR in healthy dogs. One hundred and eighteen healthy dogs of various breeds, ages, and body weights presenting to 3 referral centers. GFR was estimated in clinically healthy dogs between 1 and 14 years of age. GFR was estimated from the plasma clearance of iohexol, by a compartmental model and an empirical correction formula, normalized to body weight in kilograms or liters of extracellular fluid volume (ECFV). For data analysis, dogs were divided into body weight quartiles 1.8-12.4, 13.2-25.5, 25.7-31.6, and 32.0-70.3 kg. In the complete data set, there was no trend toward lower estimated GFR/kg or GFR/ECFV with increasing age. GFR decreased with age in dogs in the smallest weight quartile only. A significant negative linear relationship was detected between body weight and estimated GFR/kg and GFR/ECFV. Reference ranges in different weight quartiles were 1.54-4.25, 1.29-3.50, 0.95-3.36, and 1.12-3.39 mL/min/kg, respectively. Standardization to ECFV rather than kilogram body weight did not produce substantial changes in the relationships between GFR estimates and age or weight. Interpretation of GFR results for early diagnosis of renal failure should take into account the weight and the age of the patient for small dogs.
    No preview · Article · Jan 2008 · Journal of Veterinary Internal Medicine

  • No preview · Article · Jun 2006 · Atherosclerosis Supplements
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    ABSTRACT: Apolipoprotein(a) (apo(a)), which is part of the atherogenic lipoprotein Lp(a), shares structural homology with plasminogen (plg). Genes coding for plasminogen (PLG) and apo(a) (LPA) are linked and situated 40 kb apart in the telomeric region of the long arm of chromosome 6. LPA is naturally expressed only in primates and hedgehogs. Thus, access to knowledge regarding the mechanism by which LPA expression is regulated is limited due to shortage of appropriate animal models. However, mice transgenic for the human LPA gene have been produced. Lp(a) levels in man are genetically determined and not altered significantly by dietary changes. In contrast, mice transgenic for LPA-yeast artificial chromosome (LPA-YAC) have markedly reduced apo(a) levels after maintenance on a high-fat diet. LPA-YAC carries the 40 kb LPA–PLG intergenic region, which includes a putative binding site for peroxisome proliferator-activated receptor alpha (PPARα). Therefore, we examined if fibrates, which exert their effect via PPARα, could alter LPA expression in transgenic mice.
    Full-text · Article · Jun 2005 · Pathophysiology
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    ABSTRACT: In man, elevated levels of plasma plipoprotein (a) (Lp(a)) is a cardiovascular risk factor, and oxidized phospholipids are believed to play a role as modulators of inflammatory processes such as atherosclerosis. Polyamines are potent antioxidants and anti-inflammatory agents. It was therefore of interest to examine polyamines and their metabolism in LPA transgenic mice. Concentration of the polyamines putrescine, spermidine and spermine as well as the activity of peroxisomal polyamine oxidase and two other peroxisomal enzymes, acyl-CoA oxidase and catalase were measured. The mice were fed either a standard diet or a diet high in fat and cholesterol (HFHC). Some of the mice in each feeding group were in addition given aminoguanidine (AG), a specific inhibitor of diamine oxidase, which catalyses degradation of putrescine, and also inhibits non-enzymatic glycosylation of protein which is implicated in the aetiology of atherosclerosis in diabetic patients. Non-transgenic mice were used as controls. Intestinal peroxisomal polyamine oxidase activity was significantly higher in LPA transgenic mice than in the non-transgenic mice, while intestinal peroxisomal catalase activity was significantly lower. Hepatic beta-oxidation increased in Lp(a) transgenic mice fed the HFHC diet, but not in those on standard diet. Hepatic spermidine concentration was increased in all mice fed the HFHC diet compared to those fed a standard diet, while spermine concentration was decreased. With exception of the group fed only standard diet, transgenic mice showed a lower degree of hepatic steatosis than non-transgenic mice. AG had no significant effect on hepatic steatosis. The present results indicate a connection between peroxisomal enzyme activity and the presence of the human LPA gene in the murine genome. The effect may be a result of changes in oxidative processes in lipid metabolism rather than resulting from a direct effect of the LPA construct on the peroximal gene expression.
    Full-text · Article · Feb 2005 · Lipids in Health and Disease
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    ABSTRACT: Background: Lp(a) lipoprotein (Lp(a)) contains polymorphic glycoprotein, apolipoprotein(a) (apo(a)) and low density lipoprotein (LDL). The extensive homology between apo(a) and plasminogen is believed to contribute to the pathogenicity of apo(a), but the precise mechanisms by which Lp(a) participates in atherogenesis is still unknown. We used LPA-yeast artificial chromosome (LPA-YAC) transgenic mice with or without the human APOB (hAPOB) gene to study pathogenicity of apo(a)/Lp(a) and illucidate its role in regulation of serum lipid levels. Methods: Middle-aged (1-year-old) mice were fed a control (AIN-76), a high-cholesterol (HC) or a high-cholesterol/high-fat (HCHF) diet for 7 weeks. For the study of serum total apo(a) and lipid levels, mice were sampled prior to the experiment, at 2 weeks and at 7 weeks when the animals were sacrificed. Hearts with ascending aorta were fixed in formalin, embedded in gelatine and prepared for sections on a cryostat. Livers were washed in ice cold saline and submerged in RNAlater trade mark buffer and stored at -70 degrees C until mRNA analysis. Results: Wild type mice fed the control diet did not develop aortic lesions. Presence of the LPA gene was sufficient to induce development of aortic lesions, but neither coexpression of the hAPOB gene nor feeding the HC diet or the HCHF diet augmented the development of aortic lesions in LPA-YAC transgenic mice. On the control diet transgenic females had larger aortic lesion size than transgenic males. Furthermore, aortic lesions in transgenic females were associated with calcification more often than in transgenic males. Serum total cholesterol levels were higher both in wild type and LPA-YAC transgenic males than in females mainly because of higher serum high-density lipoprotein cholesterol levels. HC and HCHF feeding had more pronounced effect on total cholesterol levels in LPA-YAC/hAPOB transgenic mice than in either wild type or LPA-YAC transgenic mice, due to increased low density lipoprotein cholesterol levels. Furthermore, these diets reduced serum total apo(a) levels in both transgenic mouse lines. Conclusion: Expression of the human LPA gene in mice is sufficient to trigger development of aortic lesions. Similar frequency of calcified lesions in LPA-YAC transgenic mice with or without hAPOB gene may suggest that apo(a) is the part of the Lp(a) molecule that causes aortic calcification. The basis for reduced serum total apo(a) level in response to cholesterol feeding is not clear, but interplay between LPA and factors involved in cholesterol or bile acid homeostasis is worth of future studies.
    No preview · Article · Nov 2004 · Pathophysiology
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    ABSTRACT: The Lp(a) lipoprotein (Lp(a)) consists of the polymorphic glycoprotein apolipoprotein(a) (apo(a)), which is attached by a disulfide bond to apolipoprotein B (apoB). Apo(a), which has high homology with plasminogen, is present only in primates and hedgehogs. However, transgenic mice and rabbits with high serum apo(a) levels exist. Liver is the main site for apo(a) synthesis, but the site of removal is uncertain. To examine differences between transgenic mice expressing the LPA gene and mice capable of forming Lp(a) particles, LPA-YAC transgenic mice and hAPOB transgenic mice were crossed and their offspring examined. Comparison of LPA-YAC with LPA-YAC/hAPOB transgenic mice showed that LPA-YAC/hAPOB transgenic mice have higher serum total apo(a) and total cholesterol level than mice lacking the hAPOB gene. However, hepatic apo(a) mRNA level was higher in LPA-YAC transgenic mice than in LPA-YAC/hAPOB transgenic mice. Feeding of a high-cholesterol/high-fat diet to male LPA-YAC transgenic mice with or without the hAPOB gene resulted in reduced serum total apo(a) and hepatic apo(a) mRNA level. In conclusion, the higher serum total apo(a) level in LPA-YAC/hAPOB transgenic mice than in LPA-YAC transgenic mice is not caused by increased apo(a) synthesis. Lower hepatic apo(a) mRNA level in LPA-YAC/hAPOB than in LPA-YAC transgenic mice may suggest that the increase in total apo(a) level is a result of apo(a) accumulation in serum. Furthermore, observed higher serum total cholesterol level in LPA-YAC/hAPOB transgenic mice than either in wild type or LPA-YAC transgenic mice may further suggest that human APOB transgenicity is a factor that contributes to increased serum total apo(a) and cholesterol levels. Our results on reduced serum total apo(a) and hepatic apo(a) mRNA levels in HCHF fed male LPA-YAC transgenic mice confirm earlier findings in females, and show that there are no sex difference in mechanisms for lowering apo(a) level in response to HCHF feeding.
    Full-text · Article · Jun 2004 · Lipids in Health and Disease
  • P. Teivainen · K. Eliassen · S. Djurovic · K. Berg

    No preview · Article · Sep 2003 · Atherosclerosis Supplements
  • Knut A. Eliassen · Ragnhild Reistad · Unni Risøen · Helle F. Rønning
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    ABSTRACT: Dietary polyamines contribute to the total body polyamine pool. As polyamines are important in health and disease, it is of interest to obtain information on the food polyamine content, making it possible to calculate and manipulate the polyamine intake. In this study, meat was found to contain considerably higher amounts of polyamines than fresh fish, though the levels in fish increased rapidly upon storage and processing. Whereas some cheeses were generally high in polyamines, the content in other dairy products was low. Most fruits and vegetables normally contained low levels of polyamines, although spermidine was high in broccoli and cauliflower, and putrescine in citrus fruits. Cooking did not significantly alter the polyamine concentration. From a sensory and a nutritious point of view, these results provide a means to compose a diet high or low in polyamines.
    No preview · Article · Aug 2002 · Food Chemistry
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    ABSTRACT: Serum levels of Lp(a) lipoprotein are under genetic control and a high level is a risk factor for atherosclerotic disease. We have examined the aorta of LPA transgenic mice and their non-transgenic litter mates who had all been given a regular, not lipid fortified diet. When sacrificed, the animals had an average age of 66 weeks. Lipid lesions were observed in the aorta of 13 out of 18 LPA transgenic mice and in five out of 21 non-transgenic animals. The difference is statistically significant. We conclude that LPA transgenic mice develop lipid lesions in aorta more frequently than non-transgenic animals, even on a diet with a low fat content. LPA transgenic mice on a normal diet could be a useful animal model for the study of spontaneous human atherosclerosis, its treatment and prevention.
    No preview · Article · Aug 2002 · Atherosclerosis
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    A Svindland · K Berg · K Eliassen · R M Lawn · S Djurovic · P Aleström · T Noren · A Smith
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    ABSTRACT: The aortic root from 21 LPA transgenic mice and 18 control litter mates on cholesterol enriched chow were studied histologically for the presence of atherosclerotic lesions. Serial sections were cut and the total area of the lesions was measured by use of computerised image analysis. Lipid staining lesions were found in 17 aortas of the transgenic mice and were five times more common than in the controls. Foam cell lesions were the only type of lesion in 12 of the aortas from transgenic animals, while five animals had developed fibrofatty lesions. Immunostaining revealed monocytes/macrophages on the endothelial surface, and in the subendothelial space of foam cell lesions. In fibrofatty lesions, spindle shaped cells formed a cap around the lipid core. This study supports the view that transgenic mice expressing human apolipoprotein (a) on a high fat and cholesterol diet, are more susceptible to aortic lesions than control mice and develop early atherosclerotic lesions comparable to lesions in man. Aminoguanidin in the drinking water had no effect on the aortic lesions, but lesion size was significantly, negatively correlated with plasma glucose concentration.
    Full-text · Article · Jan 2001 · Atherosclerosis
  • K A Eliassen · O.V. Sjaastad
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    ABSTRACT: The aim of the present study was to investigate whether temporal changes in polyamine concentration and synthesis could be found in the luminal content and wall tissue of the rumen and abomasum, two organs which have entirely different growth patterns during the first month of life. In the abomasal mucosa there was a marked gradual decrease in the ornithine decarboxylase (ODC) activity during the first month of life, while the ODC activity in the ruminal mucosa was low during the whole experimental period. However, injury of the rumen wall was followed by increased ODC activity. The ODC activity in duodenal mucosa was about 10 times higher than in the ileal mucosa and the ruminal epithelium. In ruminal liquid a clear peak in ODC activity was observed during the period 51-70 days after birth. The polyamine concentration did not parallel the ODC activity, in either the ruminal epithelium or the ruminal liquid. Of the polyamines, the spermine concentration was always highest, and with the exception of duodenal mucosa, the putrescine concentration was lowest. In liver a clear decrease in spermidine concentration from day 1 to about day 60 after birth was observed. Otherwise no marked temporal changes in tissue polyamine concentrations were observed. Two and a half hours after oral administration of 14C-labelled spermine, nearly all of the radioactivity was found in the lumen of the gastrointestinal tract. On the other hand, 1 h after intravenous injection of polyamines the walls of the gastrointestinal tract were strongly labelled. In conclusion, the polyamines needed for ruminal epithelial development seem to come from sources other than the ruminal epithelium itself or the ruminal lumen.
    No preview · Article · Jul 2000 · Journal of Veterinary Medicine Series A
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    ABSTRACT: The activities of catalase, polyamine oxidase, diamine oxidase, ornithine decarboxylase, and peroxisomal beta-oxidation were assayed in homogenates from liver and small intestinal mucosa of rats which had been fed either a diet very low in polyamines or a diet containing five times the levels of dietary polyamines (putrescine, spermine, and spermidine) found in a standard rat diet. In rats fed the high polyamine diet, hepatic activities of catalase and polyamine oxidase were significantly decreased. Levels of the other activities were unchanged, except that intestinal ornithine decarboxylase was decreased. In rats treated simultaneously with clofibrate, the high polyamine diet restored activities of catalase, ornithine decarboxylase, and polyamine oxidase back to levels found in rats fed the low polyamine diet. The expected increase in activity of peroxisomal beta-oxidation was observed, although this was somewhat diminished in rats fed the high polyamine diet. Intestinal diamine oxidase activity was stimulated by clofibrate, particularly in rats fed the high polyamine diet. For the duration of the experiment (20 days), levels of putrescine, spermine, and spermidine in blood remained remarkably constant irrespective of treatment, suggesting that polyamine homeostasis is essentially independent of dietary supply of polyamines. It is suggested that intestinal absorption/metabolism of polyamines is of significance in this respect. Treatment with clofibrate appeared to alter polyamine homeostasis.
    No preview · Article · Dec 1999 · The Journal of Nutritional Biochemistry
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    J E Paulsen · R Reistad · K A Eliassen · O V Sjaastad · J Alexander
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    ABSTRACT: We have examined whether dietary polyamines influence the formation and initial growth of azoxymethane (AOM)-induced aberrant crypt foci (ACF) in rat colon. Effects of a combination of dietary polyamines at three dose levels (putrescine: 50, 280, 740 nmol/g; spermidine: 10, 261, 763 nmol/g; spermine: 1, 31, 91 nmol/g) in the polyamine-poor AIN-76A diet were studied in animals in two different experimental situations: animals treated with AOM alone and animals treated with AOM + difluoromethylornithine (DFMO), a specific inhibitor of endogenous polyamine synthesis. In both experimental situations, dietary polyamines enhanced the growth of ACF, expressed as the number of large ACF (foci with three or more aberrant crypts, ACF > or = 3), whereas the formation of ACF, expressed as the number of ACF, was apparently not altered. In animals treated with AOM alone, maximal growth enhancing effect on ACF was nearly obtained with the median level of dietary polyamine. In rats fed a low polyamine diet, basic AIN-76A, DFMO reduced the growth of AOM-induced ACF by 83%. This inhibitory effect of DFMO was counteracted by dietary polyamines in a dose-dependent manner, and it was abolished at the highest level of polyamines. In conclusion, it was demonstrated that dietary polyamines are able to enhance the growth of AOM-induced ACF. Further, dietary polyamines reversed the DFMO-caused inhibition of ACF growth, probably by compensating for the DFMO-reduced endogenous polyamine synthesis.
    Full-text · Article · Oct 1997 · Carcinogenesis
  • Harald Osmundsen · Knut Eliassen
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    ABSTRACT: Intraperitoneal injection of partially hydrogenated marine oil into rats is shown to cause marked stimulation of hepatic polyamine metabolism, as characterized by increased activity of ornithine decarboxylase (EC, and corresponding increase in tissue levels of putrescine. A maximal effect was observed about 5 hours after injection. An effect on the hepatic activity of S-adenosyl-methionine decarboxylase (EC was also observed. Of the various dietary oils examined only partially hydrogenated marine oil gave significant stimulation of polyamine metabolism. A single oral dose of partially hydrogenated marine oil gave a small increase in hepatic ornithine decarboxylase activity.
    No preview · Article · Feb 1986 · Acta pharmacologica et toxicologica
  • Knut Eliassen · Harald Osmundsen
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    ABSTRACT: The stimulation of hepatic polyamine metabolism observed 5 hr following intraperitoneal injection of clofibrate to rats was completely abolished following prior treatment with alpha-difluoromethylornithine. No induction of peroxisomal beta-oxidation could be observed 5 hr after injection of clofibrate, although appreciable induction occurred 10 hr after injection. Prior treatment with difluoromethylornithine partially inhibited this induction. On chronic treatment with clofibrate together with difluoro-methylornithine, clofibrate-dependent induction of peroxisomal beta-oxidation, as well as of the hepatomegaly, was partially inhibited. In hypophysectomized rats, no stimulation of polyamine metabolism was found following acute administration of a single dose of clofibrate. In thyroidectomized and in adrenalectomized animals, this stimulation was apparent, although the levels of activity were only some 10% of control levels. In hypophysectomized, in thyroidectomized and in adrenalectomized rats, appreciable induction of peroxisomal beta-oxidation occurred on chronic treatment with clofibrate. However, no hepatomegaly was observed in these animals.
    No preview · Article · May 1984 · Biochemical Pharmacology
  • Erik Norgaard · Reidun Sirevåg · Knut A. Eliassen

    No preview · Article · Oct 1983 · FEMS Microbiology Letters
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    ABSTRACT: When exposing rats to drinking water containing 100 p.p.m. fluoride for 8 weeks, no effect could be detected in biochemical parameters of the liver, such as the concentrations of the polyamines putrescine, spermidine and spermine; the levels of microsomal protein and cytochrome P-450; or the activities of two associated monooxygenases, aryl hydrocarbon hydroxylase and ethylmorphine N-demethylase. Neither was there any increase in plasma glutamic-oxalacetic transaminase indicative of liver damage.
    No preview · Article · Oct 1983 · Acta pharmacologica et toxicologica

Publication Stats

180 Citations
42.14 Total Impact Points


  • 2000-2012
    • Norwegian School of Veterinary Science
      • • Department of Basic Sciences and Aquatic Medicine
      • • Department of Companion Animal Clinical Sciences
      Kristiania (historical), Oslo, Norway
  • 2006
    • University of Oslo
      Kristiania (historical), Oslo, Norway
  • 1983
    • Industrial Research Institute
      Central, Louisiana, United States