Bern, Switzerland
Bern, Switzerland

Time filter

Source Type

News Article | December 2, 2016
Site: www.eurekalert.org

The "reproducibility crisis" in biomedical research has led to questions about the scientific rigor in animal research, and thus the ethical justification of animal experiments. In research publishing in the Open Access journals PLOS Biology and PLOS ONE on December 2nd, 2016, researchers from the University of Bern have assessed scientific rigor in animal experimentation in Switzerland. The study, commissioned by the Swiss Federal Food Safety and Veterinary Office (FSVO), found widespread deficiencies in the reporting of experimental methodology. In a first step, PhD student Lucile Vogt and postdoc Thomas Reichlin from the Division of Animal Welfare at the Vetsuisse Faculty in Bern screened all 1,277 approved applications for animal experiments in Switzerland in 2008, 2010 and 2012, as well as a random sample of 50 scientific publications resulting from studies described in the applications. The materials were assessed to determine whether seven basic methods that can help combat experimental bias were reported (including randomization, blinding, and sample size calculation). Appropriate use and understanding of these methods is a prerequisite for unbiased, scientifically valid results, says lead author Prof. Hanno Würbel, director of the Division of Animal Welfare. As published in their PLOS Biology study, explicit evidence that these methods were used either in the applications for animal experiments or in the subsequent publications was scarce. For example, fewer than 20% of applications and publications mentioned whether a sample size calculation had been performed (8% in applications, 0% in publications), whether the animals had been assigned randomly to treatment groups (13% in applications, 17% in publications), and whether outcome assessment had been conducted blind to treatment (3% in applications, 11% in publications). Animal experiments are authorized based on the explicit understanding that they will provide significant new knowledge and that animals will suffer no unnecessary harm. Thus, scientific rigor is a fundamental prerequisite for the ethical justification of animal experiments. Based on this study, the current practice of authorizing animal experiments appears to rest on an assumption of scientific rigor, rather than on evidence that it is applied. The authors of this study recommend more education and training in good research practice and scientific integrity for all those involved in this process. Although the initial results found that fewer than 20 percent of applications and publications used methods to control for bias, that didn't necessarily mean that more than 80 percent of animal studies failed to include methods to combat bias, and therefore use animals for potentially inconclusive research. "It is possible that the researchers did use these methods but did not mention them in their applications and publications," says study director Hanno Würbel. "So we decided to ask the researchers." The researchers used an online survey for all 1,891 animal researchers registered in the central online information system of the FSVO who were involved with ongoing experiments. Among other questions, researchers were asked what bias-reducing methods they normally use when conducting animal experiments and which of these they had explicitly reported in their latest scientific publication. According to the researchers' responses, as published in their PLOS ONE study, the use of methods against bias is considerably higher than reported in the animal research applications and publications. 86% of the participants claimed to assign animals randomly to treatment groups, but only 44% answered that they had reported this in their latest publication. The same applies to the other measures, for example, for sample size calculation (69% claimed to be doing this, but only 18% say they reported it in their latest publication) and for blinded outcome assessment (47% vs. 27%). Taken together, the researchers draw two conclusions from these results: on the one hand, reporting in animal research applications or publications may underestimate the use of bias-reducing methods. On the other hand, the researchers may overestimate their use of appropriate methods. "We found considerably fewer publications with explicit evidence of the use of measures against risks of bias than claimed by the researchers", says Würbel. For example, 44% of the participants claimed to have reported randomization in their latest publication, but Würbel's team found evidence of randomization in only 17% of publications. In your coverage please use this URL to provide access to the freely available article in PLOS Biology: http://journals. and this URL to provide access to the freely available article in PLOS ONE: http://journals. Citations: Vogt L, Reichlin TS, Nathues C, Würbel H (2016) Authorization of Animal Experiments Is Based on Confidence Rather than Evidence of Scientific Rigor. PLoS Biol 14(12): e2000598. doi:10.1371/journal.pbio.2000598 Reichlin TS, Vogt L, Würbel H (2016) The Researchers' View of Scientific Rigor--Survey on the Conduct and Reporting of In Vivo Research. PLoS ONE 11(12): e0165999. doi:10.1371/journal.pone.0165999 Funding: Swiss Food Safety and Veterinary Office (FSVO) https:/ (grant number 2.13.01). LV and TSR were fully funded through this grant. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist.


Risberg A.,Norwegian University of Life Sciences | Spadavecchia C.,Vetsuisse Faculty | Ranheim B.,Norwegian University of Life Sciences | Krontveit R.,Norwegian University of Life Sciences | Haga H.A.,Norwegian University of Life Sciences
Veterinary Journal | Year: 2014

Dexmedetomidine and lignocaine IV are used clinically to provide analgesia in horses. The aims of this study were to investigate the antinociceptive effects, plasma concentrations and sedative effects of 2, 4 and 6-μg/kg/h dexmedetomidine IV, with a bolus of 0.96-μg/kg preceding each continuous rate infusion (CRI), and 20, 40 and 60-μg/kg/min lignocaine IV, with a bolus of 550-μg/kg preceding each CRI, in 10 Swiss Warmblood horses. Electrically elicited nociceptive withdrawal reflexes were evaluated by deltoid muscle electromyography. Nociceptive threshold and tolerance were determined by electromyography and behaviour following single and repeated stimulation. Plasma concentrations of drugs were determined by liquid chromatography and mass spectrometry. Sedation was scored on a visual analogue scale. Dexmedetomidine increased nociceptive threshold to single and repeated stimulation for all CRIs, except at 2-μg/kg/h, where no increase in single stimulation nociceptive threshold was observed. Dexmedetomidine increased nociceptive tolerance to single and repeated stimulation at all CRIs. There was large individual variability in dexmedetomidine plasma concentrations and levels of sedation; the median plasma concentration providing antinociceptive effects to all recorded parameters was 0.15-ng/mL, with a range from-<0.02-ng/mL (below the lower limit of quantification) to 0.25-ng/mL. Lignocaine increased nociceptive threshold and tolerance to single and repeated stimulation at CRIs of 40 and 60-μg/kg/min, corresponding to plasma lignocaine concentrations->600-ng/mL. Only nociceptive tolerance to repeated stimulation increased at 20-μg/kg/min lignocaine. Lignocaine at 40-μg/kg/min and dexmedetomidine at 4-μg/kg/h were the lowest CRIs resulting in consistent antinociception. Lignocaine did not induce significant sedation. © 2014 Elsevier Ltd.


Di Zenzo G.,Instituto Dermopatico Dellimmacolata | Amber K.T.,University of California at Irvine | Sayar B.S.,Institute of Animal Pathology | Sayar B.S.,University of Bern | And 4 more authors.
Seminars in Immunopathology | Year: 2016

Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are two severe autoimmune bullous diseases of the mucosae and/or skin associated with autoantibodies directed against desmoglein (Dsg) 3 and/or Dsg1. These two desmosomal cadherins, typifying stratified epithelia, are components of cell adhesion complexes called desmosomes and represent extra-desmosomal adhesion receptors. We herein review the advances in our understanding of the immune response underlying pemphigus, including human leucocyte antigen (HLA) class II-associated genetic susceptibility, characteristics of pathogenic anti-Dsg antibodies, antigenic mapping studies as well as findings about Dsg-specific B and T cells. The pathogenicity of anti-Dsg autoantibodies has been convincingly demonstrated. Disease activity and clinical phenotype correlate with anti-Dsg antibody titers and profile while passive transfer of anti-Dsg IgG from pemphigus patients’ results in pemphigus-like lesions in neonatal and adult mice. Finally, adoptive transfer of splenocytes from Dsg3-knockout mice immunized with murine Dsg3 into immunodeficient mice phenotypically recapitulates PV. Although the exact pathogenic mechanisms leading to blister formation have not been fully elucidated, intracellular signaling following antibody binding has been found to be necessary for inducing cell-cell dissociation, at least for PV. These new insights not only highlight the key role of Dsgs in maintenance of tissue homeostasis but are expected to progressively change pemphigus management, paving the way for novel targeted immunologic and pharmacologic therapies. © 2015, Springer-Verlag Berlin Heidelberg.


Reusch C.E.,Vetsuisse Faculty | Padrutt I.,Vetsuisse Faculty
Veterinary Clinics of North America - Small Animal Practice | Year: 2013

Incretins (gastric inhibitory polypeptide and glucagon-like peptide 1 [GLP-1]) are hormones released from the gastrointestinal tract during food intake that potentiate insulin secretion. Native GLP-1 is quickly degraded by the enzyme dipeptidylpeptidase-4 (DPP-4), which has led to the development of GLP-1 agonists with resistance to degradation and to inhibitors of DPP-4 activity as therapeutic agents in humans with type 2 diabetes. In healthy cats, GLP-1 agonists and DPP-4 inhibitors have produced a substantial increase in insulin secretion. Although results of clinical studies are not yet available, incretin-based therapy promises to become an important new research area in feline diabetes. © 2013 Elsevier Inc.


Benz K.,Reutlingen University | Stippich C.,Reutlingen University | Fischer L.,Harlan Laboratories Ltd | Mohl K.,Harlan Laboratories Ltd | And 9 more authors.
European Spine Journal | Year: 2012

Purpose Regenerative repair is a promising new approach in treating damaged intervertebral discs. An experimental scheme was established for autologous and/or allogenic repair after massive disc injury. Methods Disc healing was promoted in 11 animals by injecting in vitro expanded autologous/homologous disc cells 2 weeks after stab injury of lumbar discs L1-2. The following control discs were used in our sheep injury model: L2-3, vehicle only; L3-4, injury only; L4-5, undamaged; and lumbar discs from four non-experimental animals. Disc cells were suspended in a biologically supportive albumin/hyaluronan two-component hydrogel solution that polymerizes when inserted in order to anchor cells at the injection site. The parameters studied were MRI, DNA, glycosaminoglycan, collagen content, histology, immunohistology for collagens type I, II and aggrecan, and mRNA expression of GAPDH, β-actin, collagen type I, II, X, aggrecan, lubricin, and IL-1β. Results All parameters demonstrated almost complete healing of the injured discs after 6 months, when compared with data from both the endogenous non-injured controls as well as from the healthy animals. Conclusion Sheep experience spontaneous recovery from disc injury. The process of endogenous repair can be enhanced by means of hydrogel-supported cells. © Springer-Verlag 2012.


PubMed | Norwegian University of Life Sciences and Vetsuisse Faculty
Type: Clinical Trial | Journal: Veterinary journal (London, England : 1997) | Year: 2014

Dexmedetomidine and lignocaine IV are used clinically to provide analgesia in horses. The aims of this study were to investigate the antinociceptive effects, plasma concentrations and sedative effects of 2, 4 and 6g/kg/h dexmedetomidine IV, with a bolus of 0.96g/kg preceding each continuous rate infusion (CRI), and 20, 40 and 60g/kg/min lignocaine IV, with a bolus of 550g/kg preceding each CRI, in 10 Swiss Warmblood horses. Electrically elicited nociceptive withdrawal reflexes were evaluated by deltoid muscle electromyography. Nociceptive threshold and tolerance were determined by electromyography and behaviour following single and repeated stimulation. Plasma concentrations of drugs were determined by liquid chromatography and mass spectrometry. Sedation was scored on a visual analogue scale. Dexmedetomidine increased nociceptive threshold to single and repeated stimulation for all CRIs, except at 2g/kg/h, where no increase in single stimulation nociceptive threshold was observed. Dexmedetomidine increased nociceptive tolerance to single and repeated stimulation at all CRIs. There was large individual variability in dexmedetomidine plasma concentrations and levels of sedation; the median plasma concentration providing antinociceptive effects to all recorded parameters was 0.15ng/mL, with a range from<0.02ng/mL (below the lower limit of quantification) to 0.25ng/mL. Lignocaine increased nociceptive threshold and tolerance to single and repeated stimulation at CRIs of 40 and 60g/kg/min, corresponding to plasma lignocaine concentrations>600ng/mL. Only nociceptive tolerance to repeated stimulation increased at 20g/kg/min lignocaine. Lignocaine at 40g/kg/min and dexmedetomidine at 4g/kg/h were the lowest CRIs resulting in consistent antinociception. Lignocaine did not induce significant sedation.


PubMed | University of Veterinary Medicine Hannover, Besamungsvereins Neustadt Aisch, Sut Kardesler Animal Breeding Center, Vetsuisse Faculty and University of Calgary
Type: Journal Article | Journal: Theriogenology | Year: 2016

The objective was to examine if there are relationships between alterations in sperm viability, reactive oxygen species (ROS) synthesis, and DNA integrity induced by cryopreservation of bovine sperm. Four ejaculates were collected from each of six bulls. Each ejaculate was diluted and divided into two aliquots; one was incubated for 24hours at 37C, and the other frozen, thawed, and incubated for 24hours at 37C. Analyses of quality of sperm were performed after 0, 3, 6, 12, and 24hours of incubation. Progressive motile sperm was determined with computer assisted sperm analysis. Percentages of plasma membrane- and acrosome-intact sperm, sperm with a high mitochondrial membrane potential, sperm showing a high degree of DNA fragmentation (%DFI), and their reactive oxygen species content were assessed with dichlorofluorescein-diacetate, dihydrorhodamine, diaminofluorescein diacetate, and mitochondrial superoxide indicator using flow cytometry. Although all other sperm parameters showed alterations (P<0.05) during the 24-hour incubation time, %DFI stayed constant (P>0.05, 0.910.23) in nonfrozen sperm. Cryopreservation induced changes of all sperm parameters (P<0.05). In contrast to all other sperm parameters, dichlorofluorescein-diacetate-fluoroescence indicating the synthesis of H2O2 showed a similar exponential rise (P<0.05) like the %DFI values in frozen sperm. In conclusion, changes of DNA integrity in frozen sperm seem to be related to synthesis of H2O2 but not to sperm viability and synthesis of other reactive oxygen species.


PubMed | University of Bern, Institute of Veterinary Bacteriology, Institute of Parasitology, Vetsuisse Faculty and University of Leipzig
Type: Journal Article | Journal: Veterinary journal (London, England : 1997) | Year: 2014

This study aimed to examine the aetiology of acute diarrhoea and the relapse rate in 100 client-owned dogs presented to a first-opinion clinic. History, physical examination, faecal testing and owner questionnaire data were collected at initial presentation (T0) and at either the time of relapse or at a recheck performed within 3 months. All dogs received treatment according to their clinical signs. Of 96 dogs that completed the study, 37 (38.5%) relapsed during the study period, 21 (21.9%) relapsed within 3 months, and 16 others (16.6%) at 3 months to 1 year after initial examination. Dogs that had undergone a change in housing location within 1 month prior to presentation and dogs <1 year old were significantly more likely to have positive parasitological analyses (P=0.02 and P=0.001, respectively). Pica was a risk factor for relapse (P=0.0002).


PubMed | University of California at Irvine, Institute of Animal Pathology, Vetsuisse Faculty and Instituto Dermopatico dellImmacolata
Type: Journal Article | Journal: Seminars in immunopathology | Year: 2016

Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are two severe autoimmune bullous diseases of the mucosae and/or skin associated with autoantibodies directed against desmoglein (Dsg) 3 and/or Dsg1. These two desmosomal cadherins, typifying stratified epithelia, are components of cell adhesion complexes called desmosomes and represent extra-desmosomal adhesion receptors. We herein review the advances in our understanding of the immune response underlying pemphigus, including human leucocyte antigen (HLA) class II-associated genetic susceptibility, characteristics of pathogenic anti-Dsg antibodies, antigenic mapping studies as well as findings about Dsg-specific B and T cells. The pathogenicity of anti-Dsg autoantibodies has been convincingly demonstrated. Disease activity and clinical phenotype correlate with anti-Dsg antibody titers and profile while passive transfer of anti-Dsg IgG from pemphigus patients results in pemphigus-like lesions in neonatal and adult mice. Finally, adoptive transfer of splenocytes from Dsg3-knockout mice immunized with murine Dsg3 into immunodeficient mice phenotypically recapitulates PV. Although the exact pathogenic mechanisms leading to blister formation have not been fully elucidated, intracellular signaling following antibody binding has been found to be necessary for inducing cell-cell dissociation, at least for PV. These new insights not only highlight the key role of Dsgs in maintenance of tissue homeostasis but are expected to progressively change pemphigus management, paving the way for novel targeted immunologic and pharmacologic therapies.


News Article | December 5, 2016
Site: www.biosciencetechnology.com

The "reproducibility crisis" in biomedical research has led to questions about the scientific rigor in animal research, and thus the ethical justification of animal experiments. In research publishing in the Open Access journals PLOS Biology and PLOS ONE on December 2nd, 2016, researchers from the University of Bern have assessed scientific rigor in animal experimentation in Switzerland. The study, commissioned by the Swiss Federal Food Safety and Veterinary Office (FSVO), found widespread deficiencies in the reporting of experimental methodology. In a first step, Ph.D. student Lucile Vogt and postdoc Thomas Reichlin from the Division of Animal Welfare at the Vetsuisse Faculty in Bern screened all 1,277 approved applications for animal experiments in Switzerland in 2008, 2010 and 2012, as well as a random sample of 50 scientific publications resulting from studies described in the applications. The materials were assessed to determine whether seven basic methods that can help combat experimental bias were reported (including randomization, blinding, and sample size calculation). Appropriate use and understanding of these methods is a prerequisite for unbiased, scientifically valid results, says lead author Prof. Hanno Würbel, director of the Division of Animal Welfare. As published in their PLOS Biology study, explicit evidence that these methods were used either in the applications for animal experiments or in the subsequent publications was scarce. For example, fewer than 20 percent of applications and publications mentioned whether a sample size calculation had been performed (8 percent in applications, 0 percent in publications), whether the animals had been assigned randomly to treatment groups (13 percent in applications, 17 percent in publications), and whether outcome assessment had been conducted blind to treatment (3 percent in applications, 11 percent in publications). Animal experiments are authorized based on the explicit understanding that they will provide significant new knowledge and that animals will suffer no unnecessary harm. Thus, scientific rigor is a fundamental prerequisite for the ethical justification of animal experiments. Based on this study, the current practice of authorizing animal experiments appears to rest on an assumption of scientific rigor, rather than on evidence that it is applied. The authors of this study recommend more education and training in good research practice and scientific integrity for all those involved in this process. Although the initial results found that fewer than 20 percent of applications and publications used methods to control for bias, that didn't necessarily mean that more than 80 percent of animal studies failed to include methods to combat bias, and therefore use animals for potentially inconclusive research. "It is possible that the researchers did use these methods but did not mention them in their applications and publications," says study director Hanno Würbel. "So we decided to ask the researchers." The researchers used an online survey for all 1,891 animal researchers registered in the central online information system of the FSVO who were involved with ongoing experiments. Among other questions, researchers were asked what bias-reducing methods they normally use when conducting animal experiments and which of these they had explicitly reported in their latest scientific publication. According to the researchers' responses, as published in their PLOS ONE study, the use of methods against bias is considerably higher than reported in the animal research applications and publications. Eighty-six percent of the participants claimed to assign animals randomly to treatment groups, but only 44 percent answered that they had reported this in their latest publication. The same applies to the other measures, for example, for sample size calculation (69 percent claimed to be doing this, but only 18 percent say they reported it in their latest publication) and for blinded outcome assessment (47 percent vs. 27 percent). Taken together, the researchers draw two conclusions from these results: on the one hand, reporting in animal research applications or publications may underestimate the use of bias-reducing methods. On the other hand, the researchers may overestimate their use of appropriate methods. "We found considerably fewer publications with explicit evidence of the use of measures against risks of bias than claimed by the researchers", says Würbel. For example, 44 percent of the participants claimed to have reported randomization in their latest publication, but Würbel's team found evidence of randomization in only 17 percent of publications.

Loading Vetsuisse Faculty collaborators
Loading Vetsuisse Faculty collaborators