Publications by authors named "Satu Sankari"

37 Publications

Effects of a high-fat diet and global aryl hydrocarbon receptor deficiency on energy balance and liver retinoid status in male Sprague-Dawley rats.

J Nutr Biochem 2021 09 5;95:108762. Epub 2021 Jun 5.

FCLAP, Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Finland.

The physiological functions of the aryl hydrocarbon receptor (AHR) are only beginning to unfold. Studies in wildtype and AHR knockout (AHRKO) mice have recently disclosed that AHR activity is required for obesity and steatohepatitis to develop when mice are fed with a high-fat diet (HFD). In addition, a line of AHRKO mouse has been reported to accumulate retinoids in the liver. Whether these are universal manifestations across species related to AHR activity level is not known yet. Therefore, we here subjected wildtype and AHRKO male rats (on Sprague-Dawley background) to HFD feeding coupled with free access to 10% sucrose solution and water; controls received a standard diet and water. Although the HFD-fed rats consumed more energy throughout the 24-week feeding regimen, they did not get overweight. However, relative weights of the brown and epididymal adipose tissues were elevated in HFD-fed rats, while that of the liver was lower in AHRKO than wildtype rats. Moreover, the four groups exhibited diet- or genotype-dependent differences in biochemical variables, some of which suggested marked dissimilarities from AHRKO mice. Expression of pro- and anti-inflammatory genes was induced in livers of HFD-fed AHRKO rats, but histologically they did not differ from others. HFD reduced the hepatic concentrations of retinyl palmitate, 9-cis-4-oxo-13,14-dihydroretinoic acid and (suggestively) retinol, whereas AHR status had no effect. Hence, the background strain/line of AHRKO rat is resistant to diet-induced obesity, and AHR does not modulate this or liver retinoid concentrations. Yet, subtle AHR-dependent differences in energy balance-related factors exist despite similar weight development.
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http://dx.doi.org/10.1016/j.jnutbio.2021.108762DOI Listing
September 2021

The effect of a raw vs dry diet on serum biochemical, hematologic, blood iron, B , and folate levels in Staffordshire Bull Terriers.

Vet Clin Pathol 2020 Jun 23;49(2):258-269. Epub 2020 Apr 23.

Faculty of Veterinary Medicine, Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland.

Background: To date, very few studies have compared the effects of different types of feeding practices on canine physiology, such as feeding exclusively dry, raw, or homemade foods.

Objectives: We aimed to report the changes in hematologic, serum biochemical, plasma folate, B , and whole blood iron levels in dogs fed two different diets.

Methods: A pilot study was developed to compare the effects of a heat-processed high carbohydrate (HPHC) and nonprocessed high-fat (NPHF) diet. A total of 33 client-owned Staffordshire Bull Terriers were used; 18 had canine atopic dermatitis, seven were healthy, and eight were grouped as "borderline" dogs since they did not fulfill at least six of Favrot's criteria. The comparisons were made between the diet groups at the end visit of the diet intervention, as well as within the diet groups during the study.

Results: Significant differences between and within the diet groups were observed, although the majority of outcomes remained within the RIs. The median time of diet intervention was 140 days. Red blood cell counts, mean cell hemoglobin concentrations, and platelet counts were significantly higher, and mean cell hemoglobin, mean cell volume, alkaline phosphatase, inorganic phosphorus, and cholesterol were significantly lower in the dogs fed the NPHF diet compared with those fed the HPHC diet after the diet trial was completed. In addition, folate, B , and iron decreased significantly in the NPHF diet group.

Conclusions: This pilot study indicated that diet had an impact on blood values, although most remained within RIs, pointing out the need for further studies.
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http://dx.doi.org/10.1111/vcp.12852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383997PMC
June 2020

Diet is a main source of vitamin D in Finnish pet rabbits (Oryctolagus cuniculus).

J Anim Physiol Anim Nutr (Berl) 2019 Sep 31;103(5):1564-1570. Epub 2019 May 31.

Faculty of Veterinary Medicine, Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland.

During the winter time in Finland, sunlight is inadequate for vitamin D synthesis. Many pet rabbits live as house rabbits with limited outdoor access even during summer and may therefore be dependent on dietary sources of vitamin D. The aims of this study were to report the serum 25-hydroxyvitamin D concentrations in Finnish pet rabbits and to identify factors that influence vitamin D status. Serum 25-hydroxyvitamin D concentrations from 140 pet rabbits were determined using a vitamin D enzyme immunoassay (EIA) kit. Eleven rabbits were excluded from the statistical analysis because of unclear dietary data. The remaining 129 rabbits were divided into groups depending on outdoor access during summer (no access n = 26, periodic n = 57, regular n = 46) as well as daily diet: little or no hay and commercial rabbit food ≤1/2 dl (n = 12); a lot of hay and no commercial food daily (n = 23); a lot of hay and commercial food <1 dl (n = 59); a lot of hay and commercial food ≥1 dl (n = 35). The range of serum 25-hydroxyvitamin D concentration was from 4.5 to 67.5 ng/ml with a mean of 26.1 ng/ml. Statistical general linear model adjusted for weight, age and season indicated that diet was associated with vitamin D concentrations (p = 0.001), but outdoor access during summer was not (p = 0.41). Mean 25-hydroxyvitamin D concentration was significantly higher in the rabbits receiving a lot of hay and commercial food ≥1 dl (33.9 ± 13.2 ng/ml) than in rabbits in other diet groups (24.0 ± 8.5 ng/ml, 21.7 ± 8.1 ng/ml, and 22.2 ± 18.0 ng/ml, respectively). This investigation showed wide variation in 25-hydroxyvitamin D concentrations among Finnish pet rabbits. Diet remains a main source since outdoor access seems to be too limited to provide adequate vitamin D synthesis for most of them, and the use of vitamin D supplements is rare.
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http://dx.doi.org/10.1111/jpn.13120DOI Listing
September 2019

Changes in biomarkers in equine synovial fluid two weeks after intra-articular hyaluronan treatment: a randomised double-blind clinical trial.

BMC Vet Res 2018 Jun 15;14(1):186. Epub 2018 Jun 15.

Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 57, 00014, Helsinki, Finland.

Background: Inflammatory and degenerative activity inside the joint can be studied in vivo via analysis of synovial fluid (SF) biomarkers, which are molecular markers of inflammatory processes and tissue turnover. The aim of this study was to investigate the response of selected biomarkers in the SF after an intra-articular (IA) high-molecular-weight non-animal stabilized hyaluronic acid (NASHA) treatment. Our hypothesis was that prostaglandin E (PGE), substance P, aggrecan chondroitin sulfate 846 epitope (CS846), and carboxypeptide of type II collagen (CPII) concentrations in SF would decrease more in the NASHA than in the placebo group. Twenty-eight clinically lame horses with positive responses to diagnostic IA anaesthesia of the metacarpophalangeal or metatarsophalangeal joints were randomized into treatment (n = 15) and control (n = 13) groups. After collection of baseline SF samples followed by IA diagnostic anaesthesia, horses in the treatment group received 3 ml of a NASHA product IA. Those in the placebo group received an equivalent volume of sterile 0.9% saline solution. The horses were re-evaluated and a second SF sample was obtained after a 2-week period.

Results: CS846 concentration decreased in the NASHA group only (P = 0.010). Both PGE and CPII concentrations decreased within the groups (PGE, P = 0.010 for the NASHA group; P = 0.027 for the placebo group; CPII, P < 0.001 for NASHA group; P = 0.009 for placebo group). No significant treatment effect for any biomarker was found between groups. NASHA induced an increase in white blood cell count; this was significant compared with baseline (P = 0.021) and the placebo group (P = 0.045).

Conclusions: Although the SF concentration of the cartilage-derived biomarker CS846 decreased in the NASHA group, no statistically significant treatment effect of any of the biomarkers were observed between treatment groups. The significant increase in SF white blood cell count after IA NASHA may indicate a mild inflammatory response. However, as no clinical adverse effects were observed, we conclude that IA NASHA was well tolerated.
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http://dx.doi.org/10.1186/s12917-018-1512-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6003042PMC
June 2018

Changes in energy metabolism, and levels of stress-related hormones and electrolytes in horses after intravenous administration of romifidine and the peripheral α-2 adrenoceptor antagonist vatinoxan.

Acta Vet Scand 2018 May 9;60(1):27. Epub 2018 May 9.

Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 57, 00014, Helsinki, Finland.

Background: Romifidine, an α-2 adrenoceptor agonist, is a widely-used sedative in equine medicine. Besides the desired sedative and analgesic actions, α-2 adrenoceptor agonists have side effects like alterations of plasma concentrations of glucose and certain stress-related hormones and metabolites in various species. Vatinoxan (previously known as MK-467), in turn, is an antagonist of α-2 adrenoceptors. Because vatinoxan does not cross the blood brain barrier in significant amounts, it has only minor effect on sedation induced by α-2 adrenoceptor agonists. Previously, vatinoxan is shown to prevent the hyperglycaemia, increase of plasma lactate concentration and the decrease of insulin and non-esterified free fatty acids (FFAs) caused by α-2 adrenoceptor agonists in different species. The aim of our study was to investigate the effects of intravenous romifidine and vatinoxan, alone and combined, on plasma concentrations of glucose and some stress-related hormones and metabolites in horses.

Results: Plasma glucose concentration differed between all intravenous treatments: romifidine (80 μg/kg; ROM), vatinoxan (200 μg/kg; V) and the combination of these (ROM + V). Glucose concentration was the highest after ROM and the lowest after V. Serum FFA concentration was higher after V than after ROM or ROM + V. The baseline serum concentration of insulin varied widely between the individual horses. No differences were detected in serum insulin, cortisol or plasma adrenocorticotropic hormone (ACTH) concentrations between the treatments. Plasma lactate, serum triglyceride or blood sodium and chloride concentrations did not differ from baseline or between the treatments. Compared with baseline, plasma glucose concentration increased after ROM and ROM + V, serum cortisol, FFA and base excess increased after all treatments and plasma ACTH concentration increased after V. Serum insulin concentration decreased after V and blood potassium decreased after all treatments.

Conclusions: Romifidine induced hyperglycaemia, which vatinoxan partially prevented despite of the variations in baseline levels of serum insulin. The effects of romifidine and vatinoxan on the insulin concentration in horses need further investigation.
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http://dx.doi.org/10.1186/s13028-018-0380-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5944056PMC
May 2018

S100A12 concentrations and myeloperoxidase activities are increased in the intestinal mucosa of dogs with chronic enteropathies.

BMC Vet Res 2018 Apr 4;14(1):125. Epub 2018 Apr 4.

Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, PO Box 57, Viikintie 49, 00014, Helsinki, Finland.

Background: Intestinal mucosal S100A12 and myeloperoxidase (MPO) are inflammatory biomarkers in humans with inflammatory bowel disease (IBD). However, these biomarkers have not been studied in the intestinal mucosa of dogs with chronic enteropathies (CE), even though dogs with CE have increased S100A12 concentrations in feces and serum. This study investigated mucosal S100A12 concentrations and MPO activities in both dogs with CE and healthy Beagles. ELISA (S100A12 concentrations) and spectrophotometric methods (MPO activity) were used. The associations of both biomarkers with canine IBD activity index (CIBDAI), histopathologic findings, clinical outcome, and serum albumin concentrations were also investigated. We studied intestinal mucosal samples originating from different intestinal regions of 40 dogs with CE and 18 healthy Beagle dogs (duodenum, ileum, colon, and cecum).

Results: Compared with healthy Beagles, mucosal S100A12 concentrations in dogs with CE were significantly higher in the duodenum (p < 0.0001) and colon (p = 0.0011), but not in the ileum (p = 0.2725) and cecum (p = 0.2194). Mucosal MPO activity of dogs with CE was significantly higher in the duodenum (p < 0.0001), ileum (p = 0.0083), colon (p < 0.0001), and cecum (p = 0.0474). Mucosal S100A12 concentrations in the duodenum were significantly higher if the inflammatory infiltrate consisted mainly of neutrophils (p = 0.0439) or macrophages (p = 0.037). Mucosal S100A12 concentrations also showed a significant association with the severity of total histopathological injury and epithelial injury in the colon (p < 0.05). Mucosal MPO activity showed a significant association (p < 0.05) with the severity of total histopathological injury, epithelial injury, and eosinophil infiltration in the duodenum. There was no significant association of both biomarkers with CIBDAI or clinical outcome.

Conclusions: This study showed that both mucosal S100A12 concentrations and MPO activities are significantly increased in the duodenum and colon of dogs with CE; mucosal MPO was also increased in the ileum and cecum. Future research should focus on assessing the clinical utility of S100A12 and MPO as diagnostic markers in dogs with CE.
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http://dx.doi.org/10.1186/s12917-018-1441-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885293PMC
April 2018

A comparison of unheated loose housing with stables on the respiratory health of weaned-foals in cold winter conditions: an observational field-study.

Acta Vet Scand 2017 Oct 26;59(1):73. Epub 2017 Oct 26.

Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, 00014, Finland.

Background: Newly weaned horses in Finland are often moved to unheated loose housing systems in which the weanlings have free access to a paddock and a shelter. This practice is considered to be good for the development of young horses. The daily temperatures can stay below - 20 °C in Finland for several consecutive weeks during the winter season. However, the effect of unheated housing in a cold climatic environment on the respiratory health of weanlings under field conditions has not been studied before. This investigation was an observational field-study comprising 60 weanlings among 11 different voluntary participant rearing farms in Finland. Weanlings were either kept in unheated loose housing systems (n = 36) or in stables (n = 24) and were clinically examined on two separate occasions 58 days apart in cold winter conditions.

Results: The odds of clinical respiratory disease were lower in the older foals (log days); OR = 0.009, P = 0.044). The plasma fibrinogen concentration was higher when the available space (m/weanling) in the sleeping hall was smaller (P = 0.014) and it was lower when the sleeping hall was not insulated (P = 0.010). The plasma fibrinogen concentrations at the second examination were lower with a body condition score above 3 (P = 0.070). Standardbreds kept in loose housing systems had a lower body condition score than Finnhorses or Standardbreds kept in stables at both examinations (P = 0.026 and P = 0.007, respectively). Haemoglobin level was lower in weanlings in loose housing systems compared to their counterparts at the first examination (P = 0.037). Finnhorses had higher white blood cell count than Standardbreds at first (P = 0.002) and at the second examination (P = 0.001).

Conclusions: Keeping weanling horses in cold loose housing systems does not seem to increase the occurrence of respiratory disease, but special attention should be focused on ventilation, air quality and feeding-practices. Our field study data suggest it might be advantageous to keep Standardbred foals born late in the season in a stable over the Finnish winter.
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http://dx.doi.org/10.1186/s13028-017-0339-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5658990PMC
October 2017

Toxicological characterisation of two novel selective aryl hydrocarbon receptor modulators in Sprague-Dawley rats.

Toxicol Appl Pharmacol 2017 07 20;326:54-65. Epub 2017 Apr 20.

Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, Finland.

The aryl hydrocarbon receptor (AHR) mediates the toxicity of dioxins, but also plays important physiological roles. Selective AHR modulators, which elicit some effects imparted by this receptor without causing the marked toxicity of dioxins, are presently under intense scrutiny. Two novel such compounds are IMA-08401 (N-acetyl-N-phenyl-4-acetoxy-5-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide) and IMA-07101 (N-acetyl-N-(4-trifluoromethylphenyl)-4-acetoxy-1,2-dihydro-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide). They represent, as diacetyl prodrugs, AHR-active metabolites of the drug compounds laquinimod and tasquinimod, respectively, which are intended for the treatment of autoimmune diseases and cancer. Here, we toxicologically assessed the novel compounds in Sprague-Dawley rats, after a single dose (8.75-92.5mg/kg) and 5-day repeated dosing at the highest doses achievable (IMA-08401: 100mg/kg/day; and IMA-07101: 75mg/kg/day). There were no overt clinical signs of toxicity, but body weight gain was marginally retarded, and the treatments induced minimal hepatic extramedullary haematopoiesis. Further, both the absolute and relative weights of the thymus were significantly decreased. Cyp1a1 gene expression was substantially increased in all tissues examined. The hepatic induction profile of other AHR battery genes was distinct from that caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The only marked alterations in serum clinical chemistry variables were a reduction in triglycerides and an increase in 3-hydroxybutyrate. Liver and kidney retinol and retinyl palmitate concentrations were affected largely in the same manner as reported for TCDD. In vitro, the novel compounds activated CYP1A1 effectively in H4IIE cells. Altogether, these novel compounds appear to act as potent activators of the AHR, but lack some major characteristic toxicities of dioxins. They therefore represent promising new selective AHR modulators.
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http://dx.doi.org/10.1016/j.taap.2017.04.020DOI Listing
July 2017

Evaluating oxidative stress, serological- and haematological status of dogs suffering from osteoarthritis, after supplementing their diet with fish or corn oil.

Lipids Health Dis 2016 Aug 26;15(1):139. Epub 2016 Aug 26.

Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 57, 00014, Helsinki, Finland.

Background: Oxidative stress plays an important role in the pathogenesis of disease, and the antioxidant physiological effect of omega-3 from fish oil may lead to improvement of canine spontaneous osteoarthritis (OA).

Methods: In this prospective randomized, controlled, double-blinded study, we assessed haematological and biochemical parameters in dogs with OA following supplementation with either a concentrated omega-3 deep sea fish oil product or corn oil. Blood samples from 77 client-owned dogs diagnosed as having OA were taken before (baseline) and 16 weeks after having orally ingested 0.2 ml/Kg bodyweight/day of deep sea fish oil or corn oil. Circulating malondialdehyde (MDA), glutathione (GSH), non-transferrin bound iron (NTBI), free carnitine (Free-Car), 8-hydroxy-2-deoxyguanosine (8-OH-dG), and serum fatty acids, haemograms and serum biochemistry were evaluated. Differences within and between groups from baseline to end, were analysed using repeated samples T-test or Wilcoxon rank test and independent samples T-test or a Mann-Whitney test.

Results: Supplementation with fish oil resulted in a significant reduction from day 0 to day 112 in MDA (from 3.41 ± 1.34 to 2.43 ± 0.92 μmol/L; P < 0.001) and an elevation in Free-Car (from 18.18 ± 9.78 to 21.19 ± 9.58 μmol/L; P = 0.004) concentrations, whereas dogs receiving corn oil presented a reduction in MDA (from 3.41 ± 1.34 to 2.41 ± 1.01 μmol/L; P = 0.001) and NTBI (from -1.25 ± 2.17 to -2.31 ± 1.64 μmol/L; P = 0.002). Both groups showed increased (albeit not significantly) GSH and 8-OH-dG blood values. Dogs supplemented with fish oil had a significant reduction in the proportions of monocytes (from 3.84 ± 2.50 to 1.77 ± 1.92 %; P = 0.030) and basophils (from 1.47 ± 1.22 to 0.62 ± 0.62 %; P = 0.012), whereas a significant reduction in platelets counts (from 316.13 ± 93.83 to 288.41 ± 101.68 × 10(9)/L; P = 0.029), and an elevation in glucose (from 5.18 ± 0.37 to 5.32 ± 0.47 mmol/L; P = 0.041) and cholesterol (from 7.13 ± 1.62 to 7.73 ± 2.03 mmol/L; P = 0.011) measurements were observed in dogs receiving corn oil.

Conclusions: In canine OA, supplementation with deep sea fish oil improved diverse markers of oxidative status in the dogs studied. As corn oil also contributed to the reduction in certain oxidative markers, albeit to a lesser degree, there was no clear difference between the two oil groups. No clinical, haematological or biochemical evidence of side effects emerged related to supplementation of either oil. Although a shift in blood fatty acid values was apparent due to the type of nutraceutical product given to the dogs, corn oil seems not to be a good placebo.
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http://dx.doi.org/10.1186/s12944-016-0304-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5002171PMC
August 2016

Genetic Panel Screening of Nearly 100 Mutations Reveals New Insights into the Breed Distribution of Risk Variants for Canine Hereditary Disorders.

PLoS One 2016 15;11(8):e0161005. Epub 2016 Aug 15.

Genoscoper Laboratories Oy, Helsinki, Finland.

Background: The growing number of identified genetic disease risk variants across dog breeds challenges the current state-of-the-art of population screening, veterinary molecular diagnostics, and genetic counseling. Multiplex screening of such variants is now technologically feasible, but its practical potential as a supportive tool for canine breeding, disease diagnostics, pet care, and genetics research is still unexplored.

Results: To demonstrate the utility of comprehensive genetic panel screening, we tested nearly 7000 dogs representing around 230 breeds for 93 disease-associated variants using a custom-designed genotyping microarray (the MyDogDNA® panel test). In addition to known breed disease-associated mutations, we discovered 15 risk variants in a total of 34 breeds in which their presence was previously undocumented. We followed up on seven of these genetic findings to demonstrate their clinical relevance. We report additional breeds harboring variants causing factor VII deficiency, hyperuricosuria, lens luxation, von Willebrand's disease, multifocal retinopathy, multidrug resistance, and rod-cone dysplasia. Moreover, we provide plausible molecular explanations for chondrodysplasia in the Chinook, cerebellar ataxia in the Norrbottenspitz, and familiar nephropathy in the Welsh Springer Spaniel.

Conclusions: These practical examples illustrate how genetic panel screening represents a comprehensive, efficient and powerful diagnostic and research discovery tool with a range of applications in veterinary care, disease research, and breeding. We conclude that several known disease alleles are more widespread across different breeds than previously recognized. However, careful follow up studies of any unexpected discoveries are essential to establish genotype-phenotype correlations, as is readiness to provide genetic counseling on their implications for the dog and its breed.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0161005PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4985128PMC
July 2017

S100A12 concentrations and myeloperoxidase activity in the intestinal mucosa of healthy dogs.

BMC Vet Res 2015 Sep 14;11:234. Epub 2015 Sep 14.

Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, PO Box 57, Viikintie 49, 00014, Helsinki, Finland.

Background: Relatively few laboratory markers have been evaluated for the detection or monitoring of intestinal inflammation in canine chronic enteropathies, including inflammatory bowel disease (IBD). Previous research found that the intestinal mucosal levels of S100A12 and myeloperoxidase (MPO), as biomarkers of gut inflammation, were elevated in human patients with IBD. To date, the S100A12 and MPO levels in intestinal mucosal samples from either healthy dogs or from dogs suffering from IBD remain unreported. Therefore, this study aimed to evaluate the mucosal S100A12 and MPO levels in four different parts of the intestine (duodenum, jejunum, ileum and colon) in 12 healthy laboratory Beagle dogs using the ELISA and spectrophotometric methods, respectively.

Results: Based on histological examinations, the recorded findings for all the samples were considered normal. The mucosal concentration of S100A12 in the ileum was significantly higher than in all other segments of the intestine (p < 0.05). MPO activity was significantly higher in the ileal, jejunal and duodenal than in colonic mucosal samples (p < 0.05). Moreover, its concentration was higher in the jejunum than in the duodenum.

Conclusions: This study showed that S100A12 and MPO are reliably detectable in canine intestinal mucosa. The assays used appeared to be sufficient to further evaluate the role of S100A12 and MPO in the pathogenesis of canine chronic enteropathies, including IBD. These biomarkers may play a role in the initial detection of gut inflammation suggesting the need for further investigations to confirm IBD or to differentiate between IBD subtypes. Understanding the role of S100A12 and MPO in the pathogenesis of chronic intestinal inflammation in future may result in an improved understanding of canine chronic intestinal inflammation.
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http://dx.doi.org/10.1186/s12917-015-0551-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4570263PMC
September 2015

Determination of the unsaturated disaccharides of hyaluronic acid in equine synovial fluid by high-performance liquid chromatography and fluorescence detection.

Acta Vet Scand 2015 Mar 4;57:12. Epub 2015 Mar 4.

Department of Equine and Small Animal Medicine, University of Helsinki, P.O. Box 57, 00014, Helsinki, Finland.

Background: The purpose of this study was to develop and validate an analytical method to determine the presence of hyaluronic acid derived disaccharides in equine synovial fluid.

Findings: A high-performance liquid chromatography method for the determination of hyaluronic acid derived unsaturated disaccharides in equine synovial fluid was developed and validated. The method is based on the measurement of unsaturated disaccharides released by digestion of linear hyaluronic acid molecules. The method showed linearity (r(2) = 0.996) over the full working concentration range 0.89-30 mg/l. Relative standard deviation of intra- and inter-day precision ranged from of 4.3-6.7% and 7.1-7.8% respectively. The detection limit was 0.3 mg/l corresponding to 20 mg/l in synovial fluid. Accuracy of the assay was 97-103%. This method was evaluated by determining the concentration of unsaturated disaccharides from hyaluronic acid in synovial fluid of horses with lameness in the metacarpo-/metatarsophalangeal joint localized with positive response to intra-articular anesthesia.

Conclusions: The described method is valid for determination of hyaluronic acid derived disaccharides in equine synovial fluid. This method was applied to a larger research project dealing with a new form of intra-articular therapy in horses with arthritic diseases.
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http://dx.doi.org/10.1186/s13028-015-0098-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4350955PMC
March 2015

Toxicological profile of ultrapure 2,2',3,4,4',5,5'-heptachlorbiphenyl (PCB 180) in adult rats.

PLoS One 2014 19;9(8):e104639. Epub 2014 Aug 19.

Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

PCB 180 is a persistent non-dioxin-like polychlorinated biphenyl (NDL-PCB) abundantly present in food and the environment. Risk characterization of NDL-PCBs is confounded by the presence of highly potent dioxin-like impurities. We used ultrapure PCB 180 to characterize its toxicity profile in a 28-day repeat dose toxicity study in young adult rats extended to cover endocrine and behavioral effects. Using a loading dose/maintenance dose regimen, groups of 5 males and 5 females were given total doses of 0, 3, 10, 30, 100, 300, 1000 or 1700 mg PCB 180/kg body weight by gavage. Dose-responses were analyzed using benchmark dose modeling based on dose and adipose tissue PCB concentrations. Body weight gain was retarded at 1700 mg/kg during loading dosing, but recovered thereafter. The most sensitive endpoint of toxicity that was used for risk characterization was altered open field behavior in females; i.e. increased activity and distance moved in the inner zone of an open field suggesting altered emotional responses to unfamiliar environment and impaired behavioral inhibition. Other dose-dependent changes included decreased serum thyroid hormones with associated histopathological changes, altered tissue retinoid levels, decreased hematocrit and hemoglobin, decreased follicle stimulating hormone and luteinizing hormone levels in males and increased expression of DNA damage markers in liver of females. Dose-dependent hypertrophy of zona fasciculata cells was observed in adrenals suggesting activation of cortex. There were gender differences in sensitivity and toxicity profiles were partly different in males and females. PCB 180 adipose tissue concentrations were clearly above the general human population levels, but close to the levels in highly exposed populations. The results demonstrate a distinct toxicological profile of PCB 180 with lack of dioxin-like properties required for assignment of WHO toxic equivalency factor. However, PCB 180 shares several toxicological targets with dioxin-like compounds emphasizing the potential for interactions.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0104639PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4138103PMC
October 2015

Diagnostic evaluation and short-term outcome as indicators of long-term prognosis in horses with findings suggestive of inflammatory bowel disease treated with corticosteroids and anthelmintics.

Acta Vet Scand 2014 Jun 3;56:35. Epub 2014 Jun 3.

Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, P,O, Box 57, FI-00014 Helsinki, Finland.

Background: Recurrent colic and unexplained weight loss despite good appetite and adequate feeding and management practices are common conditions in the horse. However, little information has been published on the systematic diagnostic evaluation, response to treatment, prognostic factors or outcome of either presentation. The aims of this study were to 1) identify possible prognostic indicators and 2) report the short- and long-term response to treatment with corticosteroid therapy of a variety of horses with a presumptive diagnosis of inflammatory bowel disease (IBD). Thirty-six horses with a history of recurrent colic and/or unexplained weight loss were screened with a detailed clinical, clinicopathological and diagnostic imaging examination. Twenty horses were subsequently selected that had findings consistent with inflammatory bowel disease based on the fulfilment of one or more of the following additional inclusion criteria: hypoproteinaemia, hypoalbuminaemia, malabsorption, an increased intestinal wall thickness on ultrasonographic examination or histopathological changes in rectal biopsy. These 20 horses were treated with a standardized larvicidal anthelmintic regime and a minimum of three weeks of corticosteroid therapy.

Results: The initial response to treatment was good in 75% (15/20) of horses, with a 3-year survival rate of 65% (13/20). The overall 3-year survival in horses that responded to initial treatment (12/15) was significantly higher (P = 0.031) than in those that did not respond to initial treatment (1/5). The peak xylose concentration was significantly (P = 0.048) higher in survivors (1.36 ± 0.44 mmol/L) than non-survivors (0.94 ± 0.36 mmol/L).

Conclusions: The overall prognosis for long-term survival in horses with a presumptive diagnosis of IBD appears to be fair to moderate, and the initial response to anthelmintic and corticosteroid therapy could be a useful prognostic indicator. The findings of the present study suggest that a low peak xylose concentration in absorption testing is associated with a less favourable prognosis, supporting the use of this test.
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http://dx.doi.org/10.1186/1751-0147-56-35DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4055252PMC
June 2014

Identification of matrix metalloproteinase-2 and -9 activities within intestinal mucosa of clinically healthy beagle dogs.

J Vet Med Sci 2014 Aug 18;76(8):1079-85. Epub 2014 Apr 18.

Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 57 (Viikintie 49), 00014 Helsinki, Finland.

Matrix metalloproteinases (MMPs) 2 and 9 are zinc-dependent endopeptidases that contribute to the control of breakdown and reconstitution of extracellular matrix under both normal and pathological conditions. The main objective of this study was to identify the presence of MMP-2 and -9 in the mucosa of the small and large intestines of clinically healthy beagle dogs using gelatin zymography technique. Intestinal mucosa samples from four different parts of the intestine (duodenum, jejunum, ileum and colon) were taken from 12 healthy laboratory beagle dogs and examined histologically. Based on WSAVA histology standards, recorded findings of all samples were considered insignificant. Pro-MMP-2 and -9 activities were found in 17/48 (35%) and 25/48 (52%) of the samples, respectively. Among four different parts of the intestine of 12 dogs, the ileum had the highest positivity rates of 7/12 (58.3%) and 8/12 (66.7%) for pro-MMP-2 and -9 activities, respectively. However, statistical analysis showed no significant difference of pro-MMP-2 and -9 activities between the separate parts of the intestine (P>0.05). None of the intestinal samples showed gelatinolytic activity corresponding to the control bands of active MMP-2 and MMP-9. This study showed that pro-MMP-2 and -9 could be detected in the intestinal mucosa of healthy dogs using zymography, which seems to be a useful tool to evaluate the role of MMP-2 and -9 in the pathogenesis of canine chronic enteropathies, including inflammatory bowel diseases.
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http://dx.doi.org/10.1292/jvms.13-0578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4155186PMC
August 2014

Development and validation of a gas chromatography-flame ionization detection method for quantifying sucrose in equine serum.

J Vet Diagn Invest 2014 Mar 11;26(2):232-9. Epub 2014 Feb 11.

1Michael Hewetson, Faculty of Veterinary Medicine, PO Box 57, 00014, University of Helsinki, Finland.

A simple and accurate method for quantifying sucrose in equine serum that can be applied to sucrose permeability testing in the horse was developed and validated using gas chromatography with flame ionization detection. The assay provided an acceptable degree of linearity, accuracy, and precision at concentrations of sucrose as low as 2.34 μmol/l and as high as 20.45 μmol/l. Percentage recovery of sucrose from serum ranged from 89% to 102%; repeatability and intermediate precision (relative standard deviation) ranged from 3.6% to 6.7% and 4.1% to 9.3%, respectively. The limit of detection was 0.73 μmol/l. No interfering peaks were observed except lactose, which gave 2 peaks, one of which overlapped partially with sucrose. To evaluate the suitability of the method for quantifying sucrose in serum samples from horses with naturally occurring gastric ulceration, 10 horses with and without naturally occurring gastric ulceration were subjected to sucrose permeability testing. All horses demonstrated an increase in serum sucrose concentration over time following oral administration of sucrose; however, the increase from baseline was significant for horses with gastric ulceration at 45 min (P = 0.0082) and 90 min (P = 0.0082) when compared with healthy horses. It was concluded that gas chromatography with flame ionization detection is a valid method for quantifying sucrose in equine serum and can be applied directly to the analysis of sucrose in equine serum as part of a larger validation study aimed at developing a blood test for the diagnosis of gastric ulcers in horses.
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http://dx.doi.org/10.1177/1040638713519640DOI Listing
March 2014

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) increases bilirubin formation but hampers quantitative hepatic conversion of biliverdin to bilirubin in rats with wild-type AH receptor.

Basic Clin Pharmacol Toxicol 2014 Jun 15;114(6):497-509. Epub 2014 Feb 15.

Department of Environmental Health, National Institute for Health and Welfare, Kuopio, Finland.

In haem degradation, haem oxygenase-1 (HO-1) first cleaves haem to biliverdin, which is reduced to bilirubin by biliverdin IXα reductase (BVR-A). The environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes hepatic accumulation of biliverdin in moderately TCDD-resistant line B (Kuopio) rats. Using line B and two TCDD-sensitive rat strains, the present study set out to probe the dose-response and biochemical mechanisms of this accumulation. At 28 days after exposure to 3-300 μg/kg TCDD in line B rats, already the lowest dose of TCDD tested, 3 μg/kg, affected serum bilirubin conjugates, and after doses ≥100 μg/kg, the liver content of bilirubin, biliverdin and their conjugates (collectively 'bile pigments') as well as HO-1 was elevated. BVR-A activity and serum bile acids were increased only by the doses of 100 and 300 μg/kg TCDD, respectively. Biliverdin conjugates correlated best with biliverdin suggesting it to be their immediate precursor. TCDD (100 μg/kg, 10 days) increased hepatic bilirubin and biliverdin levels also in TCDD-sensitive Long-Evans (Turku/AB; L-E) rats. Hepatic bilirubin and bile acids, but not biliverdin, were increased in feed-restricted L-E control rats. In TCDD-sensitive line C (Kuopio) rats, 10 μg/kg of TCDD increased the body-weight-normalized biliary excretion of bilirubin. Altogether, the results suggest that at acutely toxic doses, TCDD induces the formation of bilirubin in rats. However, concurrently, TCDD seems to hamper the quantitative conversion of biliverdin to bilirubin in line B and L-E rats' liver. Biliverdin conjugates are most likely formed as secondary products of biliverdin.
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http://dx.doi.org/10.1111/bcpt.12191DOI Listing
June 2014

Impact of diets with a high content of greaves-meal protein or carbohydrates on faecal characteristics, volatile fatty acids and faecal calprotectin concentrations in healthy dogs.

BMC Vet Res 2013 Oct 9;9:201. Epub 2013 Oct 9.

Department of Equine and Small Animal Medicine, University of Helsinki, Helsinki, Finland.

Background: Research suggests that dietary composition influences gastrointestinal function and bacteria-derived metabolic products in the dog colon. We previously reported that dietary composition impacts upon the faecal microbiota of healthy dogs. This study aims at evaluating the dietary influences on bacteria-derived metabolic products associated with the changes in faecal microbiota that we had previously reported. We fed high-carbohydrate starch based (HCS), [crude protein: 194 g/kg, starch: 438 g/kg], high-protein greaves-meal (HPGM), [crude protein: 609 g/kg, starch: 54 g/kg] and dry commercial (DC), [crude protein: 264 g/kg, starch: 277 g/kg] diets, and studied their effects on the metabolism of the colonic microbiota and faecal calprotectin concentrations in five Beagle dogs, allocated according to the Graeco-Latin square design. Each dietary period lasted for three weeks and was crossed-over with washout periods. Food intake, body weight, and faecal consistency scores, dry matter, pH, ammonia, volatile fatty acids (VFAs), and faecal canine calprotectin concentrations were determined.

Results: Faecal ammonia concentrations decreased with the HCS diet. All dogs fed the HPGM diet developed diarrhoea, which led to differences in faecal consistency scores between the diets. Faecal pH was higher with the HPGM diet. Moreover, decreases in propionic and acetic acids coupled with increases in branched-chain fatty acids and valeric acid caused changes in faecal total VFAs in dogs on the HPGM diet. Faecal canine calprotectin concentration was higher with the HPGM diet and correlated positively with valeric acid concentration.

Conclusions: The HPGM diet led to diarrhoea in all dogs, and there were differences in faecal VFA profiles and faecal canine calprotectin concentrations.
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http://dx.doi.org/10.1186/1746-6148-9-201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3851871PMC
October 2013

Unexpected gender difference in sensitivity to the acute toxicity of dioxin in mice.

Toxicol Appl Pharmacol 2012 Jul 4;262(2):167-76. Epub 2012 May 4.

Department of Food Hygiene and Environmental Health, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 66, FI-00014 University of Helsinki, Finland.

The acute toxicity of the ubiquitous environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) varies widely among species and strains. Previous studies in rats have established that females are approximately 2-fold more sensitive to TCDD lethality than males. However, there is a surprising gap in the literature regarding possible gender-related sensitivity differences in mice. In the present study, by using three substrains of TCDD-sensitive C57BL/6 mice and transgenic mice on this background, we demonstrated that: 1) in contrast to the situation in rats, female mice are the more resistant gender; 2) the magnitude of the divergence between male and female mice depends on the substrain, but can amount to over 10-fold; 3) AH receptor protein expression levels or mutations in the primary structure of this receptor are not involved in the resistance of female mice of a C57BL/6 substrain, despite their acute LD₅₀ for TCDD being over 5000 μg/kg; 4) transgenic mice that globally express the rat wildtype AH receptor follow the mouse type of gender difference; 5) in gonadectomized mice, ovarian estrogens appear to enhance TCDD resistance, whereas testicular androgens seem to augment TCDD susceptibility; and 6) the gender difference correlates best with the severity of liver damage, which is also reflected in hepatic histopathology and the expression of pro-inflammatory cytokines, especially IL-6. Hence, the two closely related rodent species most often employed in toxicological risk characterization studies, rat and mouse, represent opposite examples of the influence of gender on dioxin sensitivity, further complicating the risk assessment of halogenated aromatic hydrocarbons.
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http://dx.doi.org/10.1016/j.taap.2012.04.032DOI Listing
July 2012

Urinary recovery of orally administered chromium 51-labeled EDTA, lactulose, rhamnose, d-xylose, 3-O-methyl-d-glucose, and sucrose in healthy adult male Beagles.

Am J Vet Res 2012 May;73(5):654-8

Central Animal Laboratory, University of Turku, Turku, Finland.

Objective-To provide values for gastrointestinal permeability and absorptive function tests (GIPFTs) with chromium 51 ((51)Cr)-labeled EDTA, lactulose, rhamnose, d-xylose, 3-O-methyl-d-glucose, and sucrose in Beagles and to evaluate potential correlations between markers. Animals-19 healthy adult male Beagles. Procedures-A test solution containing 3.7 MBq of (51)Cr-labeled EDTA, 2 g of lactulose, 2 g of rhamnose, 2 g of d-xylose, 1 g of 3-O-methyl-d-glucose, and 8 g of sucrose was administered intragastrically to each dog. Urinary recovery of each probe was determined 6 hours after administration. Results-Mean ± SD (range) percentage urinary recovery was 6.3 ± 1.6% (4.3% to 9.7%) for (51)Cr-labeled EDTA, 3.3 ± 1.1% (1.7% to 5.3%) for lactulose, 25.5 ± 5.0% (16.7% to 36.9%) for rhamnose, and 58.8% ± 11.0% (40.1% to 87.8%) for 3-O-methyl-d-glucose. Mean (range) recovery ratio was 0.25 ± 0.06 (0.17 to 0.37) for (51)Cr-labeled EDTA to rhamnose, 0.13 ± 0.04 (0.08 to 0.23) for lactulose to rhamnose, and 0.73 ± 0.09 (0.60 to 0.90) for d-xylose to 3-O-methyl-d-glucose. Median (range) percentage urinary recovery was 40.3% (31.6% to 62.7%) for d-xylose and 0% (0% to 0.8%) for sucrose. Conclusions and Clinical Relevance-Reference values in healthy adult male Beagles for 6 of the most commonly used GIPFT markers were determined. The correlation between results for (51)Cr-labeled EDTA and lactulose was not as prominent as that reported for humans and cats; thus, investigators should be cautious in the use and interpretation of GIPFTs performed with sugar probes in dogs with suspected intestinal dysbiosis.
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http://dx.doi.org/10.2460/ajvr.73.5.654DOI Listing
May 2012

Comparison of 51chromium-labeled ethylenediamine tetra-acetic acid and iohexol as blood markers for intestinal permeability testing in Beagle dogs.

Vet J 2012 Apr 8;192(1):123-5. Epub 2011 Jun 8.

Central Animal Laboratory, University of Turku, Kiinamyllynkatu 10, C6, FIN-20520 Turku, Finland.

(51)Chromium-labeled ethylenediamine tetra-acetic acid ((51)Cr-EDTA) is the gold standard probe for assessing intestinal permeability (IP) in dogs, but exposure to radioactivity is a disadvantage. Iohexol is a safe contrast medium commonly used for medical imaging purposes and has been successfully applied more recently for the assessment of IP in animal models and humans. This study aimed at comparing (51)Cr-EDTA and iohexol as IP blood markers in dogs. A test solution containing (51)Cr-EDTA and iohexol was administered intragastrically to seven healthy laboratory Beagle dogs, and percentage recoveries in serum were calculated. The strong linear association (correlation, r=0.76 and linear regression, y=0.03+5.04x) between (51)Cr-EDTA and iohexol supports the potential usefulness of iohexol as an IP blood marker in dogs.
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http://dx.doi.org/10.1016/j.tvjl.2011.04.024DOI Listing
April 2012

Hepatic effects of a highly purified 2,2',3,4,4',5,5'-heptachlorbiphenyl (PCB 180) in male and female rats.

Toxicology 2011 Jun 31;284(1-3):42-53. Epub 2011 Mar 31.

Food Chemistry and Toxicology, University of Kaiserslautern; Erwin Schrödinger Strasse 52, D-67663 Kaiserslautern, Germany.

PCB 180 (2,2',3,4,4',5,5'-heptachlorobiphenyl) is a persistent and accumulating polychlorinated biphenyl abundantly present in food and the environment. In this study, we used highly purified PCB 180 (dioxinlike impurities: 2.7 ng TEQ(WHO)/g PCB 180) in a 28-day toxicity study in young adult Sprague-Dawley rats. Male and female rats were given total doses of 3, 10, 30, 100, 300, 1000 or 1700 mg/kg b.w. PCB 180 by gavage. Increased liver weights were observed at ≥ 300 mg/kg b.w. in males and females. No increases in serum ALT or ALP activities were found. A significant increase in liver pentoxyresorufin O-dealkylase (PROD) activity was found in males at ≥ 10 mg/kg b.w. and in females at ≥ 30 mg/kg b.w. In both genders, a significant induction of hepatic 7-ethoxyresorufin O-deethylase (EROD) activity was also observed in males at ≥ 10 mg/kg b.w. and in females at ≥ 300 mg/kg b.w. Western blotting showed that mainly cytochromes P450 (CYPs) 2B1/2 and 3A1 were induced while slight effects were seen on CYP1A1, CYP1A2 and CYP1B1. However, no induction of CYP1A1, 1A2 and 1B1 was found on the mRNA level, except for a slight effect in females at 1000 mg/kg b.w. Furthermore, hepatic UDP-glucuronosyltransferases (UGTs) 1A1 and 1A6 were markedly induced in males and slightly induced in females. The hepatic concentrations of apolar retinoids were decreased in males at ≥ 30 mg/kg b.w. and in females at ≥ 300 mg/kg b.w. Taken together our findings show that pure PCB 180 leads to hepatic changes in a dose range which did not cause CYP1A1 induction but causes centrilobular liver hypertrophy, affects drug-metabolizing enzymes involved in the metabolism of exogenous and endogenous substrates and leads to changes in liver retinoid levels. A benchmark dose (BMD) approach is presented in order to model lowest effective dose levels for these effects. Comparison of PCB 180 liver level related to BMDL₅ for hepatic hypertrophy in rats with human data on 'total' hepatic PCB levels in individuals without history of specific exposure suggests a relatively small margin of tissue burden in the range of 37-fold. Our results show that the highly pure non dioxin-like PCB 180 exerted strong effects different to dioxin-like compounds and that the low TEQ contamination allowed a characterization of the PCB as non-dioxinlike.
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http://dx.doi.org/10.1016/j.tox.2011.03.013DOI Listing
June 2011

Ott's protein osmotic pressure of serum and interstitial fluid in chickens (Gallus gallus): effect of age and gender.

J Exp Biol 2011 Feb;214(Pt 4):599-606

Department of Biomedicine/Physiology, Biomedicum 1, University of Helsinki, Helsinki, Finland.

Protein, or colloid, osmotic pressure (COP) is of sufficient magnitude to exert a powerful effect on Starling forces across the capillary wall. Although avian skin lacks active mechanisms for fluid transmission, such as sweating, it is now hypothesized that passive oncotic forces may regulate fluid flow and distribution in the skin and related phenomena. In this study, serum protein profiles, as well as COP in serum (COP(s)) and in suction blister fluid (COP(sbf)), were determined in juvenile, young and adult female and male chickens. For assessing COP, the Ott-Ahlqvist equation was applied. This equation can formulate the effects of multiple serum proteins on COP, according to their molecular mass. The COP values determined in chickens were lower than those previously found in mammals. COP(s) increased with age in males, and was higher in adult males than in adult females. In contrast, COP(sbf) decreased with age in females, although it was better preserved in adult males. The age-dependent decrease in COP was associated with a parallel decrease in the concentration of α(1)-globulin and albumin, and a positive correlation between packed cell volume (PCV) and COP was found. It is concluded that ageing affects Ott's COP around the vessel wall, and that an oncotic mechanism preserves plasma volume. The preservation of COP(sbf) in males suggests better maintenance of the interstitial ground substance. Females seem to lose more of a tissue's COP(s) counteracting force than males, probably as a result of gender-specific changes in the composition of the interstitial matrix. Further studies are required to elucidate the structure and function of avian lymphatics and their role in skin rheology.
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http://dx.doi.org/10.1242/jeb.048769DOI Listing
February 2011

Small intestinal permeability and serum folate and cobalamin absorption after surgical construction of permanent jejunal fistulas in laboratory beagle dogs.

Comp Med 2010 Oct;60(5):369-73

Central Animal Laboratory, University of Turku, Turku, Finland.

Permanent jejunal fistulas enable easy, noninjurious, repeated and direct administration to and collection from the small intestines of conscious laboratory dogs. This study aimed at identifying potential alterations in the small intestinal morphology and function of this canine model after the surgery required to establish the fistulas. Assays of serum folate and cobalamin and (51)Cr-EDTA permeability tests were performed before and 4 wk after experimental jejunoplasties in 14 laboratory beagle dogs. Serum folate concentrations (mean ± SD) before (12.22 ± 1.80 μg/L) and after (14.14 ± 1.70 μg/L) jejunal surgery were within reference ranges for healthy dogs, although folate concentrations were higher after surgery. The cobalamin concentrations and the 6-h urinary excretion of (51)Cr-EDTA before (573.50 ± 150.04 ng/L and 6.75 ± 1.56%, respectively) and after (496.71 ± 164.22 ng/L and 6.41 ± 1.10%) were normal for healthy dogs, and no significant differences between pre- and postsurgical values were detected. The findings of the present study indicate that the small intestinal vitamin absorption and permeability of laboratory beagle dogs with jejunal fistulas remains unimpaired.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2958205PMC
October 2010

The 51-chromium-labeled ethylenediamine tetra-acetic acid intestinal permeability blood test in healthy Beagle dogs: a comparison between serum and plasma levels.

J Vet Diagn Invest 2010 Nov;22(6):949-53

Central Animal Laboratory, University of Turku, Kiinanmyllynkatu 10, C6, FIN-20520, Turku, Finland.

A 51-chromium-labeled ethylenediamine tetra-acetic acid ((51)Cr-EDTA) permeability blood test was validated as a method to assess damage to the small intestine in dogs. The test was performed by calculating various percentages from sera after an orally ingested dose solution. The aim of the current study was to determine whether the use of serum or plasma had any influence on the results of the test. A test solution with 3.7 megabecquerel (100 µCi) of (51)Cr-EDTA was delivered through an orogastric tube to 13 healthy laboratory Beagle dogs. From each dog, 2 concurrent blood samples were withdrawn from cephalic veins using clotting-factor activator tubes for serum and heparinized tubes for plasma. The samples (n  =  26) were taken at 3 and 5 hr after administration of the test solution. Percentages of the orally ingested dose were then calculated in serum and plasma, and their relationship was assessed using correlation analysis. The mean ± standard deviation percentages in serum and plasma after 3 hr were 0.85 ± 0.43% and 0.88 ± 0.49%, respectively, whereas respective percentages in serum and plasma after 5 hr were 0.78 ± 0.52% and 0.81 ± 0.51%. The combined correlation coefficient between the percentages from the sera and plasma samples was excellent (R  =  0.98). It was concluded that the (51)Cr-EDTA permeability test in blood may be performed using serum or plasma of dogs, and the choice between the 2 samples is one of convenience.
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http://dx.doi.org/10.1177/104063871002200616DOI Listing
November 2010

The effect of contrast-enhanced ultrasound on the kidneys in eight cats.

Vet J 2011 Oct 13;190(1):109-12. Epub 2010 Oct 13.

Department of Equine and Small Animal Medicine, University of Helsinki, Finland.

Contrast-enhanced ultrasound (CEUS) of the left kidney was performed on eight non-anesthetized, young, purpose bred, domestic shorthaired cats. Each cat underwent a physical examination before and 4h and 48h after CEUS. Complete blood count (CBC), serum biochemical analysis, urinalysis, including evaluation of the enzymatic activities of urinary N-acetyl-β-d-glucosaminidase (NAG) and gamma-glutamyl transferase (GGT), were also performed. No changes were observed in CBC or serum biochemical analyses, with the exception of a decrease in blood urea concentration at 48h post-contrast ultrasound. A small elevation in NAG (U/g creatinine) was observed with a mean (SD) increase from 0.53 (0.35) to 1.43 (0.59) U/g creatinine. The magnitude of the rise was less than the circadian variation reported earlier for healthy cats. These results suggest that CEUS can be safely used to assess kidney perfusion in cats. The changes observed in laboratory values after CEUS did not appear to be related to detrimental effects on the kidneys.
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http://dx.doi.org/10.1016/j.tvjl.2010.09.007DOI Listing
October 2011

Early detection of ketoprofen-induced acute kidney injury in sheep as determined by evaluation of urinary enzyme activities.

Am J Vet Res 2010 Oct;71(10):1246-52

Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, 00170 Helsinki, Finland.

Objective: To evaluate early indicators of renal tissue destruction and changes in urinary enzyme activities in sheep during the first hours after acute kidney injury induced by administration of an overdose of an NSAID.

Animals: 12 adult female sheep.

Procedures: Acute kidney injury was induced in 6 sheep by administration of ketoprofen (30 mg/kg, IV) and detected by evaluation of urinary protein concentration, iohexol clearance, and results of histologic examination. Six sheep served as control animals. Blood and urine samples were collected for up to 24 hours after administration of ketoprofen. Plasma concentrations of urea, creatinine, albumin, and total protein; plasma activities of alkaline phosphatase, acid phosphatase, γ-glutamyl transpeptidase (GGT), matrix metalloproteinase (MMP)-2, and MMP-9; and urinary creatinine and protein concentrations, specific gravity, and activities of alkaline phosphatase, acid phosphatase, GGT lactate dehydrogenase, N-acetyl-β-D-glucosaminidase (NAG), MMP-2, and MMP-9 were measured. Urinary protein concentration and enzyme activities were normalized on the basis of urinary creatinine concentrations and reported as ratios.

Results: Many urinary enzyme-to-creatinine ratios increased before the plasma creatinine concentration exceeded the reference value. Urine NAG, lactate dehydrogenase, and acid phosphatase activities were increased beginning at 2 hours after ketoprofen administration, and alkaline phosphatase, GGT, and MMP-2 activities were increased beginning at 4 hours after ketoprofen administration. Most peak urinary enzyme-to-creatinine ratios were detected earlier than were the highest plasma creatinine and urea concentrations.

Conclusions And Clinical Relevance: Urinary enzyme activities were sensitive early indicators of acute kidney injury induced by an overdose of an NSAID in sheep.
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http://dx.doi.org/10.2460/ajvr.71.10.1246DOI Listing
October 2010

A nonhealing ulcerative skin lesion associated with Trichinella nativa infection in a cat.

J Vet Diagn Invest 2008 Nov;20(6):839-43

Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, University of Helsinki, Finland.

Trichinella spp. can infect various domestic and wild species, including companion animals. Infection occurs because of the ingestion of raw meat (e.g., infected prey). In experimental studies, cats have been found to be a very susceptible host to infection by Trichinella spp.; naturally occurring feline infections have also been reported. However, clinically apparent disease seems to be a rare manifestation of this infection in cats. The skin biopsy of an 8-year-old, neutered, male, domestic cat revealed an inflammatory granulation tissue that surrounded a well-preserved cyst that contained a Trichinella sp. larva. Distinct seropositive reaction against Trichinella spp. antigens was demonstrated by enzyme-linked immunosorbent assay and Western blot. Immunohistochemistry, by using serum from the infected cat as the source of antibody, showed strong immunostaining of Trichinella spp. larvae. During a 1-year follow-up, a postexcisional local tissue reaction was observed. This manifested as a firm, poorly circumscribed subcutaneous mass adjacent to the eye, which demonstrated clinical features and histopathologic findings indicative of chronic inflammation associated with granulation tissue and fibrodysplasia. Digestion of the muscle biopsy revealed one Trichinella sp. larva, which was identified by multiplex polymerase chain reaction as Trichinella nativa. To the authors' knowledge, this is the first documented case of trichinellosis in a cat with a nonhealing ulcerative skin lesion as the main clinical manifestation of the infection.
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http://dx.doi.org/10.1177/104063870802000625DOI Listing
November 2008

Feeding sows with high fibre diet around farrowing and early lactation: impact on intestinal activity, energy balance related parameters and litter performance.

Res Vet Sci 2009 Apr 23;86(2):314-9. Epub 2008 Aug 23.

Department of Production Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Pohjoinen Pikatie 800, 04920 Saarentaus, Finland.

The effects of fibre in diets for periparturient sows are poorly documented. Three weeks before farrowing, 41 sows (LACT) were fed a diet containing 3.8% crude fibre. Other 40 sows (FIBRE) received a diet containing 7% crude fibre. We estimated the intestinal activity of the sows with a daily qualitative evaluation of their faeces. The FIBRE group had a qualitative faeces score value of 2.1+/-1.3 and the LACT group had a value of 1.2+/-1.1 (P<0.001). Individual daily water consumption was higher in the FIBRE group than in the LACT group (P<0.001). Piglet weight gain at day 5 was higher in the FIBRE group (P<0.05). The energy balance related parameters did not differ between the treatments. Concluding, diets containing more fibre can be successfully used around farrowing reducing prolonged constipation of sows with no negative effect on their energy balance related parameters.
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http://dx.doi.org/10.1016/j.rvsc.2008.07.007DOI Listing
April 2009

Teaching veterinary clinical pathology to undergraduate students: an integrated European project.

Vet Clin Pathol 2007 Dec;36(4):336-40

Department of Animal Medicine and Surgery, University of Murcia, Spain.

Background: Veterinary clinical pathology is a relatively new and emerging discipline in Europe that has gained momentum with the recent establishment of a specialty college. In this situation, veterinary faculties may face challenges in understanding and defining what clinical pathology is and how it can best be integrated into existing curricula. In addition, many schools in Europe may not yet have available a critical mass of suitably qualified faculty capable of teaching in all areas of clinical pathology.

Objective: The main purpose of this report is to describe the goals, procedures adopted, teaching material produced, and proposed future activities of a major European initiative designed to develop a veterinary clinical pathology curriculum.

Methods: Four working subgroups were formed to establish a list of course objectives and topics and prepare a series of lectures. These contents were reviewed and discussed several times at a series of general meetings.

Results: An undergraduate course on veterinary clinical pathology was designed with course objectives, a list of topics and a CD-ROM consisting of 24 lectures.

Conclusions: The results of this project could be useful in the establishment or improvement of training programs in veterinary clinical pathology at the undergraduate level in Europe and in other places around the world. The provision of teaching resources for faculty could help to instill in veterinary students a strong understanding of the discipline and promote development of advanced training programs and career opportunities in clinical pathology in Europe.
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http://dx.doi.org/10.1111/j.1939-165x.2007.tb00437.xDOI Listing
December 2007
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