Publications by authors named "Karsten Feige"

50 Publications

CT myelographic diagnosis of ligamentum flavum hypertrophy in a Warmblood Gelding with progressive ataxia.

Vet Radiol Ultrasound 2021 Apr 5. Epub 2021 Apr 5.

Clinic for Horses, University of Veterinary Medicine, Hannover, Germany.

An 8-year-old Warmblood gelding presented with a history of progressive ataxia for 6 weeks. Intra- and intervertebral ratios measured from lateral radiographs of the cervical spine were within normal limits. Computed tomographic myelography of the cervical spine revealed focal compression of the dorsal and the ventral contrast column as well as a ventral displacement of the spinal cord within the spinal canal due to a bulging of soft tissue attenuating material in the dorsal half of the intervertebral junction of C6 and C7. Post-mortem histopathological examination confirmed chondroid metaplasia of the ligamentum flavum at C6-C7.
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http://dx.doi.org/10.1111/vru.12971DOI Listing
April 2021

Metabolic impact of weight variations in Icelandic horses.

PeerJ 2021 28;9:e10764. Epub 2021 Jan 28.

Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany.

Background: Insulin dysregulation (ID) is an equine endocrine disorder, which is often accompanied by obesity and various metabolic perturbations. The relationship between weight variations and fluctuations of the insulin response to oral glucose tests (OGT) as well as the metabolic impact of ID have been described previously. The present study seeks to characterize the concomitant metabolic impact of variations in the insulin response and bodyweight during repeated OGTs using a metabolomics approach.

Methods: Nineteen Icelandic horses were subjected to five OGTs over one year and their bodyweight, insulin and metabolic response were monitored. Analysis of metabolite concentrations depending on time (during the OGT), relative bodyweight (rWeight; defined as the bodyweight at one OGT divided by the mean bodyweight across all OGTs) and relative insulin response (rAUC; defined accordingly from the area under the insulin curve during OGT) was performed using linear models. Additionally, the pathways significantly associated with time, rWeight and rAUC were identified by rotation set testing.

Results: The results suggested that weight gain and worsening of ID activate distinct metabolic pathways. The metabolic profile associated with weight gain indicated an increased activation of arginase, while the pathways associated with time and rAUC were consistent with the expected effect of glucose and insulin, respectively. Overall, more metabolites were significantly associated with rWeight than with rAUC.
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http://dx.doi.org/10.7717/peerj.10764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847705PMC
January 2021

Metabolic profile distinguishes laminitis-susceptible and -resistant ponies before and after feeding a high sugar diet.

BMC Vet Res 2021 Jan 28;17(1):56. Epub 2021 Jan 28.

Biology and Environmental Science School, Queensland University of Technology, Brisbane, Queensland, 4000, Australia.

Background: Insulin dysregulation (ID) is a key risk factor for equine endocrinopathic laminitis, but in many cases ID can only be assessed accurately using dynamic tests. The identification of other biomarkers could provide an alternative or adjunct diagnostic method, to allow early intervention before laminitis develops. The present study characterised the metabolome of ponies with varying degrees of ID using basal and postprandial plasma samples obtained during a previous study, which examined the predictive power of blood insulin levels for the development of laminitis, in ponies fed a high-sugar diet. Samples from 10 pre-laminitic (PL - subsequently developed laminitis) and 10 non-laminitic (NL - did not develop laminitis) ponies were used in a targeted metabolomic assay. Differential concentration and pathway analysis were performed using linear models and global tests.

Results: Significant changes in the concentration of six glycerophospholipids (adj. P ≤ 0.024) and a global enrichment of the glucose-alanine cycle (adj. P = 0.048) were found to characterise the response of PL ponies to the high-sugar diet. In contrast, the metabolites showed no significant association with the presence or absence of pituitary pars intermedia dysfunction in all ponies.

Conclusions: The present results suggest that ID and laminitis risk are associated with alterations in the glycerophospholipid and glucose metabolism, which may help understand and explain some molecular processes causing or resulting from these conditions. The prognostic value of the identified biomarkers for laminitis remains to be investigated in further metabolomic trials in horses and ponies.
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http://dx.doi.org/10.1186/s12917-021-02763-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841998PMC
January 2021

Metabolic changes induced by oral glucose tests in horses and their diagnostic use.

J Vet Intern Med 2021 Jan 5;35(1):597-605. Epub 2020 Dec 5.

Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Hanover, Germany.

Background: Little is known about the implications of hyperinsulinemia on energy metabolism, and such knowledge might help understand the pathophysiology of insulin dysregulation.

Objectives: Describe differences in the metabolic response to an oral glucose test, depending on the magnitude of the insulin response.

Animals: Twelve Icelandic horses in various metabolic states.

Methods: Horses were subjected to 3 oral glucose tests (OGT; 0.5 g/kg body weight glucose). Basal, 120 and 180 minutes samples were analyzed using a combined liquid chromatography tandem mass spectrometry and flow injection analysis tandem mass spectrometry metabolomic assay. Insulin concentrations were measured using an ELISA. Analysis was performed using linear models and partial least-squares regression.

Results: The kynurenine : tryptophan ratio increased over time during the OGT (adjusted P-value = .001). A high insulin response was associated with lower arginine (adjusted P-value = .02) and carnitine (adjusted P-value = .03) concentrations. A predictive model using only baseline samples performed well with as few as 7 distinct metabolites (sensitivity, 86%; 95% confidence interval [CI], 81%-90%; specificity, 88%; 95% CI, 84%-92%).

Conclusions And Clinical Importance: Our results suggest induction of low-grade inflammation during the OGT. Plasma arginine and carnitine concentrations were lower in horses with high insulin response and could constitute potential therapeutic targets. Development of screening tools to identify insulin-dysregulated horses using only baseline blood sample appears promising.
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http://dx.doi.org/10.1111/jvim.15992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7848347PMC
January 2021

In vitro assessment of triterpenoids NVX-207 and betulinyl-bis-sulfamate as a topical treatment for equine skin cancer.

PLoS One 2020 5;15(11):e0241448. Epub 2020 Nov 5.

Equine Internal Medicine, University Equine Clinic, University of Veterinary Medicine Vienna, Vienna, Austria.

Equine sarcoid (ES) is the most prevalent skin tumor in equids worldwide. Additionally, aging grey horses frequently suffer from equine malignant melanoma (EMM). Current local therapies targeting these skin tumors remain challenging. Therefore, more feasible topical treatment options should be considered. In order to develop a topical therapy against ES and EMM, betulinyl-bis-sulfamate and NVX-207, derivatives of the naturally occurring betulin and betulinic acid, respectively, were evaluated for their antiproliferative (crystal violet staining assay), cytotoxic (MTS assay) and apoptotic (AnnexinV staining, cell cycle investigations) effects on primary ES cells, EMM cells and equine dermal fibroblasts in vitro. The more potent derivative was assessed for its in vitro penetration and permeation on isolated equine skin within 30 min and 24 h using Franz-type diffusion cells and HPLC analysis. Betulinyl-bis-sulfamate and NVX-207 inhibited the proliferation and metabolism in ES cells, EMM cells and fibroblasts significantly (p < 0.001) in a time- and dose-dependent manner. NVX-207 had superior anticancer effects compared to betulinyl-bis-sulfamate. Both compounds led to the externalization of phosphatidylserines on the cell membrane and DNA fragmentation, demonstrating that the effective mode of action was apoptosis. After 48 h of treatment with NVX-207, the number of necrotic cells was less than 2% in all cell types. Detected amounts of NVX-207 in the different skin layers exceeded the half-maximal inhibitory concentrations calculated by far. Even though data obtained in vitro are auspicious, the results are not unconditionally applicable to the clinical situation. Consequently, in vivo studies are required to address the antitumoral effects of topically applied NVX-207 in ES and EMM patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241448PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643960PMC
December 2020

Concentration profiles and safety of topically applied betulinic acid and NVX-207 in eight healthy horses-A randomized, blinded, placebo-controlled, crossover pilot study.

J Vet Pharmacol Ther 2021 Jan 26;44(1):47-57. Epub 2020 Aug 26.

University Equine Clinic, University of Veterinary Medicine Vienna, Vienna, Austria.

The naturally occurring betulinic acid (BA) and its derivative NVX-207 show anticancer effects against equine malignant melanoma (EMM) cells and a potent permeation in isolated equine skin in vitro. The aim of the study was to determine the in vivo concentration profiles of BA and NVX-207 in equine skin and assess the compounds' local and systemic tolerability with the intent of developing a topical therapy against EMM. Eight horses were treated percutaneously in a crossover design with 1% BA, 1% NVX-207 or a placebo in a respective vehicle twice a day for seven consecutive days with a seven-day washout period between each formulation. Horses were treated at the neck and underneath the tail. Concentration profiles of the compounds were assessed by high-performance liquid chromatography in the cervical skin. Clinical and histopathological examinations and blood analyses were performed. Higher concentrations of NVX-207 were found in the skin compared to BA. Good systemic tolerability and only mild local adverse effects were observed in all three groups. This study substantiates the topical application of BA and NVX-207 in further clinical trials with horses suffering from EMM; however, penetration and permeation of the compounds may be altered in skin affected by tumors.
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http://dx.doi.org/10.1111/jvp.12903DOI Listing
January 2021

Weight loss is linearly associated with a reduction of the insulin response to an oral glucose test in Icelandic horses.

BMC Vet Res 2020 May 24;16(1):151. Epub 2020 May 24.

Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Bünteweg 9, 30559, Hanover, Germany.

Background: Insulin dysregulation (ID) goes along with lasting or transient hyperinsulinemia able to trigger equine laminitis, a painful and crippling foot condition. Promoting weight loss through dietary changes and physical activity is currently the main option to prevent this disease. This study aimed at describing the relationship between weight variations and the level of ID as determined by oral glucose tests (OGT). Therefore, the insulin response of 19 Icelandic horses to repeated OGTs was retrospectively analysed considering the variations in their body weight.

Results: There was a strong linear relationship between variations in body weight and variations in the total insulin response to OGT as approximated by the area under the curve of insulin (p < 0.001). As indicated by a weighted least squares model, the insulin response decreased by 22% for 5% weight loss on average. However some horses did not respond to weight loss with a reduction of their insulin response to OGT. Additionally, a high correlation between 120 min serum insulin concentration and total insulin response was observed (r = 0.96, p < 0.001).

Conclusions: The results corroborate that weight loss is effective against ID and allow for a better quantification of the expected improvement of the insulin response after weight loss. However, it is unclear why some horses did not respond as expected. The high correlation between the 120 min insulin concentration and total insulin response suggests that insulin status can be accurately determined and monitored with only few samples in a practical setting.
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http://dx.doi.org/10.1186/s12917-020-02356-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7245939PMC
May 2020

Antimicrobial Usage in Horses: The Use of Electronic Data, Data Curation, and First Results.

Front Vet Sci 2020 29;7:216. Epub 2020 Apr 29.

Department of Biometry, Epidemiology and Information Processing, WHO Collaborating Centre for Research and Training for Health in the Human-Animal-Environment Interface, University for Veterinary Medicine Hannover, Hanover, Germany.

The usage of antimicrobial drugs (AMs) leads to an increase in antimicrobial resistance (AMR). Although different antimicrobial usage (AMU) monitoring programs exist for livestock animals in Germany, there is no such system for horses. However, with the increasing usage of electronic practice management software (EPMS), it is possible to analyze electronic field data generated for routine purposes. The aim of this study was to generate AMU data for German horses with data from the Clinic for Horses (CfH), University of Veterinary Medicine Hannover (TiHo), and in addition to show that different processes of data curation are necessary to provide results, especially considering quantitative indices. In this investigation, the number of antimicrobial doses used and the amount and percentage of active ingredients applied were calculated. Data contained all drugs administered between the 1st of January and the 31st of December 2017. A total of 2,168 horses were presented for veterinary care to the CfH and 34,432 drug applications were documented for 1,773 horses. Of these, 6,489 (18.85%) AM applications were documented for 837 (47.21%) horses. In 2017, 162.33 kg of active ingredients were documented. The most commonly used antibiotic classes were sulfonamides (84.32 kg; 51.95 %), penicillins (30.11 kg; 18.55%) and nitroimidazoles (24.84 kg; 15.30%). In 2017, the proportion of Critically Important Antibiotics (CIA)-Highest Priority used was 0.15% (0.24 kg) and the proportion of CIA-High Priority used was 20.85% (33.85 kg). Of the total 9,402 entries of antimicrobial active ingredients, the three with the largest number used were sulfonamides [ = 2,798 (29.76%)], trimethoprim [ = 2,757 (29.76%)] and aminoglycosides [ = 1,381 (14.69%)]. Comparison between Administered Daily Dose (ADA) and Recommended Daily Dose of CfH (RDD), showed that 3.26% of ADA were below RDD, 3.18% exceeded RDD and 93.55% were within the range around RDD. This study shows that data generated by an EPMS can be evaluated once the method is set up and validated. The method can be transferred to evaluate data from the EPMS of other clinics or animal species, but the transferability depends on the quality of AMU documentation and close cooperation with respective veterinarians is essential.
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http://dx.doi.org/10.3389/fvets.2020.00216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200993PMC
April 2020

Betulinic acid shows anticancer activity against equine melanoma cells and permeates isolated equine skin in vitro.

BMC Vet Res 2020 Feb 5;16(1):44. Epub 2020 Feb 5.

University Equine Clinic, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210, Vienna, Austria.

Background: Equine malignant melanoma (EMM) is a frequently occurring dermoepidermal tumor in grey horses. Currently available therapies are either challenging or inefficient. Betulinic acid (BA), a naturally occurring triterpenoid, is a promising compound for cancer treatment. To evaluate the potential of BA as a topical therapy for EMM, its anticancer effects on primary equine melanoma cells and dermal fibroblasts and its percutaneous permeation through isolated equine skin were assessed in vitro.

Results: BA showed antiproliferative and cytotoxic effects on both primary equine melanoma cells and fibroblasts in a time- and dose-dependent manner. The lowest half-maximal inhibitory concentrations were obtained 96 h after the beginning of drug exposure (12.7 μmol/L and 23.6 μmol/L for melanoma cells eRGO1 and MelDuWi, respectively, in cytotoxicity assay). High concentrations of the compound were reached in the required skin layers in vitro.

Conclusion: BA is a promising substance for topical EMM treatment. Further clinical studies in horses are necessary to assess safety and antitumoral effects in vivo.
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http://dx.doi.org/10.1186/s12917-020-2262-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003431PMC
February 2020

Characterization of Equine Parvovirus in Thoroughbred Breeding Horses from Germany.

Viruses 2019 10 18;11(10). Epub 2019 Oct 18.

Department of Molecular and Medical Virology, Faculty of Medicine, Ruhr-University Bochum, 44801 Bochum, Germany.

An equine parvovirus-hepatitis (EqPV-H) has been recently identified in association with equine serum hepatitis, also known as Theiler's disease. The disease was first described by Arnold Theiler in 1918 and is often observed with parenteral use of blood products in equines. However, natural ways of viral circulation and potential risk factors for transmission still remain unknown. In this study, we investigated the occurrence of EqPV-H infections in Thoroughbred horses in northern and western Germany and aimed to identify potential risk factors associated with viral infections. A total of 392 Thoroughbreds broodmares and stallions were evaluated cross-sectionally for the presence of anti-EqPV-H antibodies and EqPV-H DNA using a luciferase immunoprecipitation assay (LIPS) and a quantitative PCR, respectively. In addition, data regarding age, stud farm, breeding history, and international transportation history of each horse were collected and analysed. An occurrence of 7% EqPV-H DNA positive and 35% seropositive horses was observed in this study cohort. The systematic analysis of risk factors revealed that age, especially in the group of 11-15-year-old horses, and breeding history were potential risk factors that can influence the rate of EqPV-H infections. Subsequent phylogenetic analysis showed a high similarity on nucleotide level within the sequenced Thoroughbred samples. In conclusion, this study demonstrates circulating EqPV-H infections in Thoroughbred horses from central Europe and revealed age and breeding history as risk factors for EqPV-H infections.
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http://dx.doi.org/10.3390/v11100965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6833105PMC
October 2019

Chronic equine hepacivirus infection in an adult gelding with severe hepatopathy.

Vet Med Sci 2019 08 3;5(3):372-378. Epub 2019 Jul 3.

Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany.

Background: Equine hepacivirus (EqHV) in equids represents the closest homologue to hepatitis C virus (HCV) infecting humans. A majority of HCV infected patients develop a chronic course of infection leading to liver fibrosis, cirrhosis and liver failure. However, in horses mostly transient mild subclinical infections are reported for EqHV to date.

Objectives: EqHV can be involved in chronic liver diseases of horses.

Methods: Biochemical parameters in serum samples were measured. Viral load was determined using qPCR. Next generation sequencing (NGS) of serum was performed. Liver tissue was stained with haematoxylin and eosin and analysed for viral RNA with fluorescent in situ-hybridization.

Results: The horse showed symptoms of severe hepatopathy and was chronically infected with EqHV. Viral RNA was detectable in the liver during disease. To rule out other infectious agents NGS was performed and showed the highest abundance for EqHV. The identified virus sequence was similar to other circulating equine hepaciviruses.

Conclusions: EqHV can be associated with liver disease in horses. Whether it causes the disease or contributes in a multifactorial manner needs further investigation.
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http://dx.doi.org/10.1002/vms3.181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682795PMC
August 2019

Response to letter to editor regarding ECEIM consensus statement on equine metabolic syndrome.

J Vet Intern Med 2019 05 16;33(3):1125-1126. Epub 2019 Apr 16.

Equine Clinic, Internal Medicine, Faculty of Veterinary Medicine, Justus-Liebig-University of Giessen, Giessen, Germany.

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http://dx.doi.org/10.1111/jvim.15503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6524088PMC
May 2019

ECEIM consensus statement on equine metabolic syndrome.

J Vet Intern Med 2019 Mar 6;33(2):335-349. Epub 2019 Feb 6.

Equine Clinic, Internal Medicine, Faculty of Veterinary Medicine, Justus-Liebig-University of Giessen, Giessen, Germany.

Equine metabolic syndrome (EMS) is a widely recognized collection of risk factors for endocrinopathic laminitis. The most important of these risk factors is insulin dysregulation (ID). Clinicians and horse owners must recognize the presence of these risk factors so that they can be targeted and controlled to reduce the risk of laminitis attacks. Diagnosis of EMS is based partly on the horse's history and clinical examination findings, and partly on laboratory testing. Several choices of test exist which examine different facets of ID and other related metabolic disturbances. EMS is controlled mainly by dietary strategies and exercise programs that aim to improve insulin regulation and decrease obesity where present. In some cases, pharmacologic aids might be useful. Management of an EMS case is a long-term strategy requiring diligence and discipline by the horse's carer and support and guidance from their veterinarians.
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http://dx.doi.org/10.1111/jvim.15423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6430910PMC
March 2019

First detection and frequent occurrence of Equine Hepacivirus in horses on the African continent.

Vet Microbiol 2018 Sep 21;223:51-58. Epub 2018 Jul 21.

Department of Companion Animal Clinical Studies, Faculty of Veterinary Science, University of Pretoria, Private Bag X04, Onderstepoort, 0110, Pretoria, South Africa; Department for Companion Animals and Horses, University of Veterinary Medicine, Vienna, Veterinärplatz 1, 1210, Vienna, Austria; Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Bünteweg 9, 30559, Hannover, Germany. Electronic address:

Since the discovery of equine hepacivirus (EqHV) in 2011, the virus has been detected in horse populations from more than twelve countries across five continents. EqHV seroprevalence has been reported to be as high as 61.8% and EqHV ribonucleic acid (RNA) prevalence to range between 0.9% and 34.1%. Molecular and serological indications of EqHV infection have never been reported in equids on the African continent. Therefore, investigation of EqHV prevalence in South African horses and subsequent viral genetic characterization contribute to a better understanding of the global epidemiology of this virus. In a cross-sectional study, serum samples from 454 Thoroughbred foals (aged 58-183 days) were analysed for anti-EqHV non-structural protein 3 (NS3)-specific antibodies (abs) with a luciferase immunoprecipitation system (LIPS) and for EqHV RNA by quantitative real-time polymerase chain reaction (qRT-PCR). Farms of origin (n = 26) were situated in South Africa's Western Cape Province. The associations between EqHV infection state and farm of origin, foal gender and foal age were subsequently described. Furthermore, nested PCRs were performed on parts of the 5'UTR, NS3 and NS5B genes of 17 samples. Samples were sequenced and phylogenetic analyses were conducted. The population's seroprevalence was 83.70% and RNA was detected in 7.93% of samples. Increasing foal age was associated with decreasing ab prevalence and increasing prevalence of EqHV RNA. Sequences from South African EqHV strains did not show in-depth clustering with published sequences of EqHV isolates from particular continents. In conclusion, EqHV is present in the South African Thoroughbred population and appears more prevalent than reported in other horse populations worldwide.
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http://dx.doi.org/10.1016/j.vetmic.2018.07.015DOI Listing
September 2018

Lower plasma trans-4-hydroxyproline and methionine sulfoxide levels are associated with insulin dysregulation in horses.

BMC Vet Res 2018 May 2;14(1):146. Epub 2018 May 2.

Institute of Animal Science, Faculty of Agricultural Sciences, University of Hohenheim, Fruwirthstraße 35, 70593, Stuttgart, Germany.

Background: Insulin dysregulation in horses is a metabolic condition defined by high insulin concentrations in the blood and peripheral insulin resistance. This hyperinsulinemia is often associated with severe damage in the hooves, resulting in laminitis. However, we currently lack detailed information regarding the potential involvement of particular metabolic pathways in pathophysiological causes and consequences of equine insulin dysregulation. This study aimed to assess the dynamic metabolic responses given to an oral glucose test (OGT) in insulin-sensitive and insulin-dysregulated horses by a targeted metabolomics approach to identify novel metabolites associated with insulin dysregulation.

Results: Oral glucose testing triggered alterations in serum insulin (26.28 ± 4.20 vs. 422.84 ± 88.86 μIU/mL, p < 0.001) and plasma glucose concentrations (5.00 ± 0.08 vs. 9.43 ± 0.44 mmol/L, p < 0.001) comparing basal and stimulated conditions after 180 min. Metabolome analyses indicated OGT-induced changes in short-chain acylcarnitines (6.00 ± 0.53 vs. 3.99 ± 0.23 μmol/L, p < 0.001), long-chain acylcarnitines (0.13 ± 0.004 vs. 0.11 ± 0.002 μmol/L, p < 0.001) and amino acids (2.18 ± 0.11 vs. 1.87 ± 0.08 μmol/L, p < 0.05). Kynurenine concentrations increased (2.88 ± 0.18 vs. 3.50 ± 0.19 μmol/L, p < 0.01), whereas spermidine concentrations decreased during OGT (0.09 ± 0.004 vs. 0.08 ± 0.002 μmol/L, p < 0.01), indicating proinflammatory conditions after oral glucose load. Insulin dysregulation was associated with lower concentrations of trans-4-hydroxyproline (4.41 ± 0.29 vs. 6.37 ± 0.71 μmol/L, p < 0.05) and methionine sulfoxide (0.40 ± 0.06 vs. 0.87 ± 0.13 μmol/L, p < 0.01; mean ± SEM in insulin-dysregulated vs. insulin-sensitive basal samples, respectively), two metabolites which are related to antioxidant defense mechanisms.

Conclusion: Oral glucose application during OGT resulted in profound metabolic and proinflammatory changes in horses. Furthermore, insulin dysregulation was predicted in basal samples (without OGT) by pathways associated with trans-4-hydroxyproline and methionine sulfoxide, suggesting that oxidative stress and oxidant-antioxidant disequilibrium are contributing factors to insulin dysregulation. The present findings provide new hypotheses for future research to better understand the underlying pathophysiology of insulin dysregulation in horses.
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http://dx.doi.org/10.1186/s12917-018-1479-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5930486PMC
May 2018

Retrospective analysis of insulin responses to standard dosed oral glucose tests (OGTs) via naso-gastric tubing towards definition of an objective cut-off value.

Acta Vet Scand 2018 Jan 19;60(1). Epub 2018 Jan 19.

Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Bünteweg 9, 30559, Hannover, Germany.

Background: Insulin dysregulation (ID) with basal or postprandial hyperinsulinemia is one of the key findings in horses and ponies suffering from the equine metabolic syndrome (EMS). Assessment of ID can easily be performed in clinical settings by the use of oral glucose challenge tests. Oral glucose test (OGT) performed with 1 g/kg bodyweight (BW) glucose administered via naso-gastric tube allows the exact administration of a defined glucose dosage in a short time. However, reliable cut-off values have not been available so far. Therefore, the aim of the study was to describe variations in insulin response to OGT via naso-gastric tubing and to provide a clinical useful cut-off value for ID when using the insulin quantification performed with an equine-optimized insulin enzyme-linked immunosorbent assay.

Results: Data visualization revealed no clear separation in the serum insulin concentration of insulin sensitive and insulin dysregulated horses during OGT. Therefore, a model based clustering method was used to circumvent the use of an arbitrary limit for categorization. This method considered all data-points for the classification, taking into account the individual insulin trajectory during the OGT. With this method two clusters were differentiated, one with low and one with high insulin responses during OGT. The cluster of individuals with low insulin response was consistently detected, independently of the initialization parameters of the algorithm. In this cluster the 97.5% quantile of insulin is 110 µLU/mL at 120 min. We suggest using this insulin concentration of 110 µLU/mL as a cut-off value for samples obtained at 120 min in OGT.

Conclusion: OGT performed with 1 g/kg BW glucose and administration via naso-gastric tubing can easily be performed under clinical settings. Application of the cut-off value of 110 µLU/mL at 120 min allows assessment of ID in horses.
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http://dx.doi.org/10.1186/s13028-018-0358-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5775575PMC
January 2018

Germline mutation within COL2A1 associated with lethal chondrodysplasia in a polled Holstein family.

BMC Genomics 2017 Oct 10;18(1):762. Epub 2017 Oct 10.

Institute for Animal Breeding and Genetics, University of Veterinary Medicine Hannover, Hannover, Germany.

Background: The bulldog calf syndrome is a lethal form of the inherited congenital chondrodysplasias. Among the progeny of the polled Holstein bull Energy P cases of lethal chondrodysplasia were observed. Pedigrees of the cases and the frequency of 3/8 cases among the offspring of Energy P at our teaching and experimental farm Ruthe (LuFG Ruthe) supported the assumption of a germline mutation with a mosaic of normal and defective sperm.

Results: All three malformed calves were examined using necropsy, histopathology and computed tomography scanning. The phenotypic appearance of the affected calves was highly similar; they presented with severe disproportionate dwarfism and reduced body weight. The syndrome was characterized by brachygnathia superior, bilateral palatoschisis, shortening and compression of the body due to malformed vertebrae, in their size reduced and malformed ribs and reduced length of the long bones of the limbs. The bones had small irregular diaphyses and enlarged epiphyses. Whole genome sequencing of one bulldog calf, sperm of its sire Energy P and a normal progeny of Energy P identified a deleterious missense mutation (g.32476082G > A, c.2986G > A, ss2019324576) within COL2A1 on bovine chromosome (BTA) 5. Sanger sequencing confirmed the ss2019324576 variant in the affected calves and sperm of Energy P. This mutation is located within the collagen triple helix repeat and causes an exchange of glycine to serine (p.996G > S) in COL2A1. This private single nucleotide variant (SNV) was present as a gonadal mosaic in sperm of the bull. All affected calves were in a heterozygous state whereas normal half-siblings and all dams of the progeny from Energy P were missing this SNV. Validation in polled Holstein bulls and normal Holstein calves randomly sampled from several herds and from the LuFG Ruthe confirmed this SNV as private.

Conclusions: The identified spontaneous missense mutation within COL2A1 is most likely the cause of lethal chondrodysplasia in the progeny of Energy P through a dominant negative effect. This example suggests that it would be beneficial to conduct whole genome sequencing of sperm from bulls widely used in artificial insemination in order to detect germline mosaicism.
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http://dx.doi.org/10.1186/s12864-017-4153-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5633883PMC
October 2017

Frequent occurrence of nonprimate hepacivirus infections in Thoroughbred breeding horses - A cross-sectional study for the occurrence of infections and potential risk factors.

Vet Microbiol 2017 May 4;203:315-322. Epub 2017 Apr 4.

Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Bünteweg 9, 30559 Hannover, Germany. Electronic address:

Recently, several new hepaciviruses have been identified of which the nonprimate hepacivirus (NPHV) - the closest relative to hepatitis C virus (HCV) discovered to date - is highly prevalent in horses. However, potential risk factors for the transmission of NPHV among horses remain still unknown. Therefore, the objective of this study was to investigate the occurrence of NPHV infections in Thoroughbreds in northern and western Germany and to identify potential risk factors associated with NPHV infections. Using a cross-sectional study design, a total of 733 serum samples from Thoroughbred broodmares and stallions from northern and western Germany were analyzed for the presence of anti-NPHV nonstructural protein 3 (NS3) antibodies and NPHV RNA using the luciferase immunoprecipitation system (LIPS) and a quantitative real-time PCR, respectively. Information regarding signalment, stud farm, breeding history and international transportation history of each horse were collected and evaluated. A frequent occurrence of NPHV was found in the study population with 453 seropositive horses (61.8%) and 134 horses (18.3%) carrying NPHV RNA. Furthermore, statistical analysis revealed that the probability of being infected decreased for horses with a transportation history with increasing age by 20% each year. For horses that stayed in Germany no association between age and infection could be observed. In conclusion, the high occurrence of NPHV infections in breeding Thoroughbreds suggests circulating NPHV infections, endemic herds or persistent shedding in these animals and revealed the association of age and international transportation as risk factor for NPHV infections.
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http://dx.doi.org/10.1016/j.vetmic.2017.03.030DOI Listing
May 2017

Insulin signaling in various equine tissues under basal conditions and acute stimulation by intravenously injected insulin.

Domest Anim Endocrinol 2017 10 12;61:17-26. Epub 2017 May 12.

Institute of Animal Science, Faculty of Agricultural Sciences, University of Hohenheim, Fruwirthstraße 35, 70599 Stuttgart, Germany.

The aim of the study was to analyze key proteins of the equine insulin signaling cascade and their extent of phosphorylation in biopsies from muscle tissue (MT), liver tissue (LT), and nuchal AT, subcutaneous AT, and retroperitoneal adipose tissues. This was investigated under unstimulated (B1) and intravenously insulin stimulated (B2) conditions, which were achieved by injection of insulin (0.1 IU/kg bodyweight) and glucose (150 mg/kg bodyweight). Twelve warmblood horses aged 15 ± 6.8 yr (yr), weighing 559 ± 79 kg, and with a mean body condition score of 4.7 ± 1.5 were included in the study. Key proteins of the insulin signaling cascade were semiquantitatively determined using Western blotting. Furthermore, modulation of the cascade was assessed. The basal expression of the proteins was only slightly influenced during the experimental period. Insulin induced a high extent of phosphorylation of insulin receptor in LT (P < 0.01) but not in MT. Protein kinase B and mechanistic target of rapamycin expressed a higher extent of phosphorylation in all tissues in B2 biopsies. Adenosine monophosphate protein kinase, as a component related to insulin signaling, expressed enhanced phosphorylation in MT (P < 0.05) and adipose tissues (nuchal AT P < 0.05; SCAT P < 0.01; retroperitoneal adipose tissue P < 0.05), but not in LT at B2. Tissue-specific variations in the acute response of insulin signaling to intravenously injected insulin were observed. In conclusion, insulin sensitivity in healthy horses is based on a complex concerted action of different tissues by their variations in the molecular response to insulin.
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http://dx.doi.org/10.1016/j.domaniend.2017.04.003DOI Listing
October 2017

Immune protection against reinfection with nonprimate hepacivirus.

Proc Natl Acad Sci U S A 2017 03 8;114(12):E2430-E2439. Epub 2017 Mar 8.

Institute for Experimental Virology, Twincore Centre for Experimental and Clinical Infection Research, Medical School Hannover (MHH)-Helmholtz Centre for Infection Research (HZI), 30625 Hannover, Germany;

Hepatitis C virus (HCV) displays a restricted host species tropism and only humans and chimpanzees are susceptible to infection. A robust immunocompetent animal model is still lacking, hampering mechanistic analysis of virus pathogenesis, immune control, and prophylactic vaccine development. The closest homolog of HCV is the equine nonprimate hepacivirus (NPHV), which shares similar features with HCV and thus represents an animal model to study hepacivirus infections in their natural hosts. We aimed to dissect equine immune responses after experimental NPHV infection and conducted challenge experiments to investigate immune protection against secondary NPHV infections. Horses were i.v. injected with NPHV containing plasma. Flow cytometric analysis was used to monitor immune cell frequencies and activation status. All infected horses became viremic after 1 or 2 wk and viremia could be detected in two horses for several weeks followed by a delayed seroconversion and viral clearance. Histopathological examinations of liver biopsies revealed mild, periportally accentuated infiltrations of lymphocytes, macrophages, and plasma cells with some horses displaying subclinical signs of hepatitis. Following viral challenge, an activation of equine immune responses was observed. Importantly, after a primary NPHV infection, horses were protected against rechallenge with the homologous as well as a distinct isolate with only minute amounts of circulating virus being detectable.
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http://dx.doi.org/10.1073/pnas.1619380114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5373355PMC
March 2017

Acute and chronic infections with nonprimate hepacivirus in young horses.

Vet Res 2016 Sep 22;47(1):97. Epub 2016 Sep 22.

Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Bünteweg 9, 30559, Hannover, Germany.

The recently discovered nonprimate hepacivirus (NPHV) naturally infects horses and is the closest known homolog of hepatitis C virus to date. Within a follow-up study acute field infections were monitored in four young Thoroughbred horses until the ages of 12-13 months. Serum samples were analyzed for the presence of NPHV RNA and anti-NPHV NS3 antibodies and liver specific parameters were evaluated. The four young horses were not able to clear infection, but remained chronically infected for the entire monitored time period despite the presence of NPHV specific antibodies.
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http://dx.doi.org/10.1186/s13567-016-0381-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5034468PMC
September 2016

Vertical transmission of hepatitis C virus-like non-primate hepacivirus in horses.

J Gen Virol 2016 10 26;97(10):2540-2551. Epub 2016 Jul 26.

Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Bünteweg 9, 30559 Hannover, Germany.

Non-primate hepacivirus (NPHV), a recently discovered hepatotropic virus infecting horses, is phylogenetically the closest known homologue of hepatitis C virus (HCV). The main route for acquiring HCV infection in childhood is vertical transmission. However, nothing is known about the natural mode of transmission for NPHV. To investigate the possibility of vertically transmitted NPHV infection in horses, 20 Thoroughbred broodmares and their foals were monitored during foaling season 2015 until 6 months post-partum. Prepartal serum was taken from the mares, and during foaling umbilical cord blood and colostrum samples were collected. Postnatal serum samples were taken from the foals after delivery. In addition, serum was taken at 3 and 6 months after foaling from all mares and foals. Samples were analysed for the presence of NPHV RNA by quantitative real-time PCR and for the presence of anti-NPHV NS3 antibodies by luciferase immunoprecipitation system. Identified NPHV isolates were sequenced and phylogenetic analysis of the viral glycoproteins was used to track the course of naturally occurring infections and the circulation of distinct isolates within the herd. At parturition, 16 mares were seropositive, including four viraemic mares. Vertical transmission occurred in one of these four mare-foal pairs. Interestingly, NPHV isolates of newly infected foals and mares after 3 and 6 months cluster in their respective pasture herds suggesting another horizontal route of transmission.
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http://dx.doi.org/10.1099/jgv.0.000561DOI Listing
October 2016

Frequent presence of hepaci and pegiviruses in commercial equine serum pools.

Vet Microbiol 2016 1;182:8-14. Epub 2015 Nov 1.

Institute for Virology, Department of Infectious Diseases, University of Veterinary Medicine Hannover, Germany. Electronic address:

Novel viruses belonging to the genera Hepacivirus and Pegivirus have recently been discovered in horses and other animal species. Viral genomes of non-primate hepaciviruses (NPHV), equine pegivirus 1 (EPgV 1) and Theiler's disease associated virus (TDAV) were detected in a horse serum routinely used for cell culture propagation in our laboratory. Therefore, a study was carried out to further investigate the presence of these human Hepatitis C virus (HCV) related viruses in equine serum based products used in veterinary medicine and for research and to characterize the viral genomes. Without exception all commercially available equine sera purchased for cell culture propagation (n=6) were tested positive for NPHV, EPgV 1 or TDAV genomes by qRT-PCR. Molecular analyses of one single commercial horse serum from Europe confirmed multiple viral genomes, including two TDAV genomes significantly different from the only published TDAV sequence. Furthermore, multiple batches of horse serum pools (n=35) collected for manufacturing of biological products turned out to be positive for NPHV and EPgV 1 genomes. Nevertheless, the final commercial products (n=9) were exclusively tested qRT-PCR negative. Field samples (n=119) obtained from two premises located in the same region as the donor horses were analyzed, demonstrating the frequent presence of NPHV and EPgV 1, but the absence of TDAV genomes. The presence of NPHV, EPgV 1 and TDAV in commercial equine sera and serum based products could have considerable consequences for biosecurity and may also bias the outcome of research studies conducted with related viruses.
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http://dx.doi.org/10.1016/j.vetmic.2015.10.032DOI Listing
September 2016

Phenotypic classification of variability of non-syndromic congenital cleft lip and jaw in Vorderwald × Montbéliarde cattle.

Acta Vet Scand 2015 Dec 15;57:87. Epub 2015 Dec 15.

University of Veterinary Medicine Hannover, Foundation, Institute for Animal Breeding and Genetics, Bünteweg 17p, 30559, Hannover, Germany.

Background: Non-syndromic congenital cleft lip and jaw (CLJ) is a condition reported in several cattle breeds, but a detailed classification system does not exist for cattle. The objective of the present study was to describe the phenotypic variability of this orofacial malformation in Vorderwald × Montbéliarde cattle. For this purpose, a classification system of CLJ was developed on examination of five orofacial structures: (1) lips, (2) the processus (proc.) nasalis of the os incisivum, (3) the dental plate with adjacent segments of the hard palate, (4) the facial bones (os incisivum, os maxillare, os nasale and os palatinum) and (5) the mandibles. Each structure was given a score reflecting the degree of the lesion from absent (score 0) to severe.

Results: Nine cases were included in the study and they shared absence of the abaxial rostral part of the processus (proc.) nasalis of the os incisivum, partial loss of the rugae palatinae and the dental plate. A sigmoid curvature of the rostral lower jaw as well as a lateral deviation of the face and rostral lower jaw was highly variable in their expression. These deformations were present in eight of nine cases. In addition to the complete CLJ, three animals had an incomplete CLJ on the contralateral site with variable defects of the rostral part of the proc. nasalis of the os incisivum.

Conclusions: A complete CLJ is obviously accompanied by a loss of parts of the proc. nasalis of the os incisivum. Extent and localization of the missing parts of the proc. nasalis were similar in all cases. A precise classification of the various CLJ forms is necessary.
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http://dx.doi.org/10.1186/s13028-015-0177-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4678477PMC
December 2015

Local and systemic effect of transfection-reagent formulated DNA vectors on equine melanoma.

BMC Vet Res 2015 Jun 11;11:132. Epub 2015 Jun 11.

Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany.

Background: Equine melanoma has a high incidence in grey horses. Xenogenic DNA vaccination may represent a promising therapeutic approach against equine melanoma as it successfully induced an immunological response in other species suffering from melanoma and in healthy horses. In a clinical study, twenty-seven, grey, melanoma-bearing, horses were assigned to three groups (n = 9) and vaccinated on days 1, 22, and 78 with DNA vectors encoding for equine (eq) IL-12 and IL-18 alone or in combination with either human glycoprotein (hgp) 100 or human tyrosinase (htyr). Horses were vaccinated intramuscularly, and one selected melanoma was locally treated by intradermal peritumoral injection. Prior to each injection and on day 120, the sizes of up to nine melanoma lesions per horse were measured by caliper and ultrasound. Specific serum antibodies against hgp100 and htyr were measured using cell based flow-cytometric assays. An Analysis of Variance (ANOVA) for repeated measurements was performed to identify statistically significant influences on the relative tumor volume. For post-hoc testing a Tukey-Kramer Multiple-Comparison Test was performed to compare the relative volumes on the different examination days. An ANOVA for repeated measurements was performed to analyse changes in body temperature over time. A one-way ANOVA was used to evaluate differences in body temperature between the groups. A p-value < 0.05 was considered significant for all statistical tests applied.

Results: In all groups, the relative tumor volume decreased significantly to 79.1 ± 26.91% by day 120 (p < 0.0001, Tukey-Kramer Multiple-Comparison Test). Affiliation to treatment group, local treatment and examination modality had no significant influence on the results (ANOVA for repeated measurements). Neither a cellular nor a humoral immune response directed against htyr or hgp100 was detected. Horses had an increased body temperature on the day after vaccination.

Conclusions: This is the first clinical report on a systemic effect against equine melanoma following treatment with DNA vectors encoding eqIL12 and eqIL18 and formulated with a transfection reagent. Addition of DNA vectors encoding hgp100 respectively htyr did not potentiate this effect.
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http://dx.doi.org/10.1186/s12917-015-0422-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4464139PMC
June 2015

Assessment of cross-species transmission of hepatitis C virus-related non-primate hepacivirus in a population of humans at high risk of exposure.

J Gen Virol 2015 Sep 3;96(9):2636-2642. Epub 2015 Jun 3.

Institute of Experimental Virology, Twincore - Centre of Experimental and Clinical Infection Research, Feodor-Lynen-Str. 7, 30625 Hannover, Germany.

The recent discovery of hepatitis C virus (HCV)-related viruses in different animal species has raised new speculations regarding the origin of HCV and the possibility of a zoonotic source responsible for the endemic HCV transmission. As a consequence, these new findings prompt questions regarding the potential for cross-species transmissions of hepaciviruses. The closest relatives to HCV discovered to date are the non-primate hepaciviruses (NPHVs), which have been described to infect horses. To evaluate the risk of a potential zoonotic transmission, we analysed NPHV RNA and antibodies in humans with occupational exposure to horses in comparison with a low-risk group. Both groups were negative for NPHV RNA, even though low seroreactivities against various NPHV antigens could be detected irrespective of the group. In conclusion, we did not observe evidence of NPHV transmission between horses and humans.
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http://dx.doi.org/10.1099/vir.0.000208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4857452PMC
September 2015

Local and systemic effect of transfection-reagent formulated DNA vectors on equine melanoma.

BMC Vet Res 2015 May 14;11:107. Epub 2015 May 14.

Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany.

Background: Equine melanoma has a high incidence in grey horses. Xenogenic DNA vaccination may represent a promising therapeutic approach against equine melanoma as it successfully induced an immunological response in other species suffering from melanoma and in healthy horses. In a clinical study, twenty-seven, grey, melanoma-bearing, horses were assigned to three groups (n = 9) and vaccinated on days 1, 22, and 78 with DNA vectors encoding for equine (eq) IL-12 and IL-18 alone or in combination with either human glycoprotein (hgp) 100 or human tyrosinase (htyr). Horses were vaccinated intramuscularly, and one selected melanoma was locally treated by intradermal peritumoral injection. Prior to each injection and on day 120, the sizes of up to nine melanoma lesions per horse were measured by caliper and ultrasound. Specific serum antibodies against hgp100 and htyr were measured using cell based flow-cytometric assays. An Analysis of Variance (ANOVA) for repeated measurements was performed to identify statistically significant influences on the relative tumor volume. For post-hoc testing a Tukey-Kramer Multiple-Comparison Test was performed to compare the relative volumes on the different examination days. An ANOVA for repeated measurements was performed to analyse changes in body temperature over time. A one-way ANOVA was used to evaluate differences in body temperature between the groups. A p-value < 0.05 was considered significant for all statistical tests applied.

Results: In all groups, the relative tumor volume decreased significantly to 79.1 ± 26.91% by day 120 (p < 0.0001, Tukey-Kramer Multiple-Comparison Test). Affiliation to treatment group, local treatment and examination modality had no significant influence on the results (ANOVA for repeated measurements). Neither a cellular nor a humoral immune response directed against htyr or hgp100 was detected. Horses had an increased body temperature on the day after vaccination.

Conclusions: This is the first clinical report on a systemic effect against equine melanoma following treatment with DNA vectors encoding eqIL12 and eqIL18 and formulated with a transfection reagent. Addition of DNA vectors encoding hgp100 respectively htyr did not potentiate this effect.
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http://dx.doi.org/10.1186/s12917-015-0414-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4429833PMC
May 2015

Clinical course of infection and viral tissue tropism of hepatitis C virus-like nonprimate hepaciviruses in horses.

Hepatology 2015 Feb 5;61(2):447-59. Epub 2015 Jan 5.

Institute for Experimental Virology, TWINCORE Center for Experimental and Clinical Infection Research Hannover, Germany.

Unlabelled: Hepatitis C virus (HCV) has a very narrow species and tissue tropism and efficiently replicates only in humans and the chimpanzee. Recently, several studies identified close relatives to HCV in different animal species. Among these novel viruses, the nonprimate hepaciviruses (NPHV) that infect horses are the closest relatives of HCV described to date. In this study, we analyzed the NPHV prevalence in northern Germany and characterized the clinical course of infection and viral tissue tropism to explore the relevance of HCV-related horse viruses as a model for HCV infection. We found that approximately 31.4% of 433 horses were seropositive for antibodies (Abs) against NPHV and approximately 2.5% carried viral RNA. Liver function analyses revealed no indication for hepatic impairment in 7 of 11 horses. However, serum gamma-glutamyl transferase (GGT) concentrations were mildly elevated in 3 horses, and 1 horse displayed even highly elevated GGT levels. Furthermore, we observed that NPHV infection could be cleared in individual horses with a simultaneous emergence of nonstructural (NS)3-specific Abs and transient elevation of serum levels of liver-specific enzymes indicative for a hepatic inflammation. In other individual horses, chronic infections could be observed with the copresence of viral RNA and NS3-specific Abs for over 6 months. For the determination of viral tissue tropism, we analyzed different organs and tissues of 1 NPHV-positive horse using quantitative real-time polymerase chain reaction and fluorescent in situ hydridization and detected NPHV RNA mainly in the liver and at lower amounts in other organs.

Conclusion: Similar to HCV infections in humans, this work demonstrates acute and chronic stages of NPHV infection in horses with viral RNA detectable predominantly within the liver.
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http://dx.doi.org/10.1002/hep.27440DOI Listing
February 2015

Agreement of high definition oscillometry with direct arterial blood pressure measurement at different blood pressure ranges in horses under general anaesthesia.

Vet Anaesth Analg 2015 May 23;42(3):286-91. Epub 2014 Jul 23.

Small Animal Clinic, University of Veterinary Medicine Hannover Foundation, Hannover, Germany.

Objective: To determine the agreement of high definition oscillometry (HDO) with direct arterial blood pressure measurements in normotensive, hypotensive and hypertensive horses during general anaesthesia.

Study Design: Experimental study.

Animals: Seven healthy warmblood horses, aged 3-11 years, weighing 470-565 kg.

Methods: Measurements from a HDO device with the cuff placed around the base of the tail were compared with pressures measured invasively from the facial artery. High blood pressures were induced by intravenous (IV) administration of dobutamine (5 μg kg(-1) minute(-1)) over ten minutes followed by norepinephrine (0.1 mg kg(-1) IV) and low pressures by increasing the inspired fraction of isoflurane and administration of nitroglycerine (0.05 mg kg(-1) IV). For analysis three pressure levels were determined: high (MAP>110 mmHg), normal (60 mmHg
Results: A total of 245 paired measurements of systolic (SAP), mean (MAP) and diastolic (DAP) pressures were obtained. The HDO device underestimated blood pressure at hypertensive and normotensive levels and overestimated blood pressure at hypotensive levels. Best agreement was obtained for SAP and MAP within normotensive limits. At normotension, bias ± standard deviation for SAP, MAP and DAP were 0.1 ± 19.4 mmHg, 0.5 ± 14.0, 4.7 ± 15.6, respectively. At high pressure levels bias and SD were 26.1 ± 37.3 (SAP), 4.2 ± 19.4 (MAP), 1.5 ± 16.8 (DAP) and at low pressures -20.0 ± 20.9 (SAP), -11.4 ± 19.6 (MAP), -4.7 ± 20.1 (DAP), with HDO measurements at a MAP <50 mmHg often failing.

Conclusion And Clinical Relevance: Good agreement with invasive arterial blood pressures was obtained with HDO at normotensive levels in horses. At high and low pressure ranges HDO was unreliable. Therefore, if haemodynamic instability is expected, invasive measurement remains preferable.
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http://dx.doi.org/10.1111/vaa.12203DOI Listing
May 2015

Development of a method for analysis of ketamine and norketamine enantiomers in equine brain and cerebrospinal fluid by capillary electrophoresis.

Electrophoresis 2014 Oct 10;35(19):2863-9. Epub 2014 Jul 10.

Clinical Pharmacology Laboratory, University of Bern, Bern, Switzerland.

Ketamine and norketamine are being transported across the blood brain barrier and are also entering from blood into cerebrospinal fluid (CSF). Enantioselective distributions of these compounds in brain and CSF have never been determined. The enantioselective CE based assay previously developed for equine plasma was adapted to the analysis of these compounds in equine brain via use of an acidic pre-extraction of interferences prior to liquid/liquid extraction at alkaline pH. CSF can be treated as plasma. With 100 mg of brain tissue and 0.5 mL of CSF or plasma, assay conditions for up to 30 nmol/g and 6 μM, respectively, of each enantiomer with LOQs of 0.5 nmol/g and 0.1 μM, respectively, were established and the assays were applied to equine samples. CSF and plasma samples analyzed stemmed from anesthetized patient horses and brain, CSF and plasma were obtained from anesthetized horses that were euthanized with an overdose of pentobarbital. Data obtained indicate that ketamine and norketamine enantiomers are penetrating into brain and CSF with those of ketamine being more favorably transported than norketamine, whereas metabolites of norketamine are hindered. More work is required to properly investigate possible stereoselectivities of the ketamine metabolism and transport of metabolites from blood into brain tissue and CSF.
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http://dx.doi.org/10.1002/elps.201400093DOI Listing
October 2014