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Pathogenicity Of An Emergent, Ovine Abortifacient Campylobacter Jejuni Clone Orally Inoculated Into Pregnant Guinea Pigs, Eric R. Burrough, Orhan Sahin, Paul J. Plummer, Qijing Zhang, Michael J. Yaeger 2017 Iowa State University

Pathogenicity Of An Emergent, Ovine Abortifacient Campylobacter Jejuni Clone Orally Inoculated Into Pregnant Guinea Pigs, Eric R. Burrough, Orhan Sahin, Paul J. Plummer, Qijing Zhang, Michael J. Yaeger

Paul Plummer

Objective—To compare pathogenicity of an emergent abortifacient Campylobacter jejuni (IA 3902) with that of reference strains after oral inoculation in pregnant guinea pigs. Animals—58 pregnant guinea pigs. Procedures—12 animals were challenged IP with C jejuni IA 3902 along with 5 sham-inoculated control animals to confirm abortifacient potential. Once pathogenicity was confirmed, challenge via oral inoculation was performed whereby 12 guinea pigs received IA 3902, 12 received C jejuni isolated from ovine feces (OF48), 12 received a fully sequenced human C jejuni isolate (NCTC 11168), and 5 were sham-inoculated control animals. After abortions, guinea pigs were euthanized; samples ...


Comparison Of Two Commercial Ovine Campylobacter Vaccines And An Experimental Bacterin In Guinea Pigs Inoculated With Campylobacter Jejuni, Eric R. Burrough, Orhan Sahin, Paul J. Plummer, Kevin D. DiVerde, Qijing Zhang, Michael J. Yaeger 2017 Iowa State University

Comparison Of Two Commercial Ovine Campylobacter Vaccines And An Experimental Bacterin In Guinea Pigs Inoculated With Campylobacter Jejuni, Eric R. Burrough, Orhan Sahin, Paul J. Plummer, Kevin D. Diverde, Qijing Zhang, Michael J. Yaeger

Paul Plummer

Objective—To compare efficacy of 2 commercial ovine Campylobacter vaccines and an experimental bacterin in guinea pigs following IP inoculation with Campylobacter jejuni IA3902. Animals—51 female guinea pigs. Procedures—Pregnant and nonpregnant animals were randomly assigned to 1 of 4 treatment groups and administered a commercial Campylobacter vaccine labeled for prevention of campylobacteriosis in sheep via two 5-mL doses 14 days apart (vaccine A; n = 13), another labeled for prevention of campylobacteriosis via two 2-mL doses (vaccine B; 12), an experimental bacterin prepared from the challenge strain (12), or a sham vaccine (14). Ten days later, animals were challenged ...


Altered Electroretinogram B-Wave In A Suffolk Sheep Experimentally Infected With Scrapie, J. D. Smith, J. J. Greenlee, A. N. Hamir, M. H. West Greenlee 2017 U.S. Department of Agriculture

Altered Electroretinogram B-Wave In A Suffolk Sheep Experimentally Infected With Scrapie, J. D. Smith, J. J. Greenlee, A. N. Hamir, M. H. West Greenlee

Jodi Smith

TRANSMISSIBLE spongiform encephalopathies (TSEs) are a group of fatal neurodegenerative diseases in which an abnormal isoform of the cellular prion protein (PrPSc) accumulates in tissues of the central nervous system. Accumulation of PrPSc occurs in the retina, a rostral projection of the central nervous system, of both natural and nonnatural host species with TSEs (Foster and others 1999, Spraker and others 2002, Head and others 2003, 2005, Hamir and others 2004, 2005, Kercher and others 2004, Greenlee and others 2006, Hortells and others 2006). In retinas from scrapie-affected sheep, PrPSc accumulation is primarily observed in the inner and outer plexiform ...


Temporal Resolution Of Misfolded Prion Protein Transport, Accumulation, Glial Activation, And Neuronal Death In The Retinas Of Mice Inoculated With Scrapie, M. Heather West Greenlee, Melissa Lind, Robyn Kokemuller, Najiba Mammadova, Naveen Kondru, Sireesha Manne, Jodi Smith, Anumantha Kanthasamy, Justin Greenlee 2017 Iowa State University

Temporal Resolution Of Misfolded Prion Protein Transport, Accumulation, Glial Activation, And Neuronal Death In The Retinas Of Mice Inoculated With Scrapie, M. Heather West Greenlee, Melissa Lind, Robyn Kokemuller, Najiba Mammadova, Naveen Kondru, Sireesha Manne, Jodi Smith, Anumantha Kanthasamy, Justin Greenlee

Jodi Smith

Currently, there is a lack of pathological landmarks to describe the progression of prion disease in vivo. Our goal was to use an experimental model to determine the temporal relationship between the transport of misfolded prion protein (PrPSc) from the brain to the retina, the accumulation of PrPSc in the retina, the response of the surrounding retinal tissue, and loss of neurons. Retinal samples from mice inoculated with RML scrapie were collected at 30, 60, 90, 105, and 120 days post inoculation (dpi) or at the onset of clinical signs of disease (153 dpi). Retinal homogenates were tested ...


Comparison Of Humoral And T-Cell-Mediated Immune Responses To A Single Dose Of Bovela® Live Double Deleted Bvdv Vaccine Or To A Field Bvdv Strain, Ratree Platt, Lyle Kesl, Christian Guidarini, Chong Wang, James A. Roth 2017 Iowa State University

Comparison Of Humoral And T-Cell-Mediated Immune Responses To A Single Dose Of Bovela® Live Double Deleted Bvdv Vaccine Or To A Field Bvdv Strain, Ratree Platt, Lyle Kesl, Christian Guidarini, Chong Wang, James A. Roth

Chong Wang

The objective of this study was to determine and compare the humoral and cellular immune responses of calves exposed to a single dose of Bovela® bovine viral diarrhea virus (BVDV) live double deleted vaccine or a field strain virus (FSV) of BVDV type 2 (strain 890). Thirty seronegative, colostrum-deprived 5 month-old Holstein steer calves that tested negative for persistent BVDV by ear notch immunohistochemistry and seronegative to BVDV types 1 and 2 were used. Calves were screened by multi-parameter flow cytometry (MP-FCM) 1 week before vaccination to ensure that they were negative for T cell responses to the BVDV types ...


Comparison Of Humoral And T-Cell-Mediated Immune Responses To A Single Dose Of Bovela® Live Double Deleted Bvdv Vaccine Or To A Field Bvdv Strain, Ratree Platt, Lyle Kesl, Christian Guidarini, Chong Wang, James A. Roth 2017 Iowa State University

Comparison Of Humoral And T-Cell-Mediated Immune Responses To A Single Dose Of Bovela® Live Double Deleted Bvdv Vaccine Or To A Field Bvdv Strain, Ratree Platt, Lyle Kesl, Christian Guidarini, Chong Wang, James A. Roth

Veterinary Microbiology and Preventive Medicine Publications

The objective of this study was to determine and compare the humoral and cellular immune responses of calves exposed to a single dose of Bovela® bovine viral diarrhea virus (BVDV) live double deleted vaccine or a field strain virus (FSV) of BVDV type 2 (strain 890). Thirty seronegative, colostrum-deprived 5 month-old Holstein steer calves that tested negative for persistent BVDV by ear notch immunohistochemistry and seronegative to BVDV types 1 and 2 were used. Calves were screened by multi-parameter flow cytometry (MP-FCM) 1 week before vaccination to ensure that they were negative for T cell responses to the BVDV types ...


The Effects Of Methamphetamine Exposure On Cardiovascular Development In Combination With Hypoxia In Danio Rerio, Sarah Donaldson 2017 University of Akron

The Effects Of Methamphetamine Exposure On Cardiovascular Development In Combination With Hypoxia In Danio Rerio, Sarah Donaldson

Honors Research Projects

The purpose of this study was to determine the effects of methamphetamine combined with hypoxia on the development and function of the cardiovascular system in Danio rerio embryos. It was hypothesized that the combined effect of the drug and decreased oxygen concentration would result in decreased cardiac parameters due to underdevelopment of the ventricle and vessels resulting from cardiomyopathy and lack of blood flow to tissues. It was found that methamphetamine exposure correlated to an increase in stroke volume, caudal artery and vein diameters and RBC velocities alone, while having a multiplicative effect of increasing arterial RBC velocity when combined ...


Animal Carcinogenicity Studies: 1. Poor Human Predictivity, Andrew Knight, Jarrod Bailey, Jonathan Balcombe 2016 Animal Consultants International

Animal Carcinogenicity Studies: 1. Poor Human Predictivity, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jarrod Bailey, Ph.D.

The regulation of human exposure to potentially carcinogenic chemicals constitutes society’s most important use of animal carcinogenicity data. Environmental contaminants of greatest concern within the USA are listed in the Environmental Protection Agency’s (EPA’s) Integrated Risk Information System (IRIS) chemicals database. However, of the 160 IRIS chemicals lacking even limited human exposure data but possessing animal data that had received a human carcinogenicity assessment by 1 January 2004, we found that in most cases (58.1%; 93/160), the EPA considered animal carcinogenicity data inadequate to support a classification of probable human carcinogen or non-carcinogen. For the ...


Animal Carcinogenicity Studies: Implications For The Reach System, Andrew Knight, Jarrod Bailey, Jonathan Balcombe 2016 Animal Consultants International

Animal Carcinogenicity Studies: Implications For The Reach System, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jarrod Bailey, Ph.D.

The 2001 European Commission proposal for the Registration, Evaluation and Authorisation of Chemicals (REACH) aims to improve public and environmental health by assessing the toxicity of, and restricting exposure to, potentially toxic chemicals. The greatest benefits are expected to accrue from decreased cancer incidences. Hence the accurate identification of chemical carcinogens must be a top priority for the REACH system. Due to a paucity of human clinical data, the identification of potential human carcinogens has conventionally relied on animal tests. However, our survey of the US Environmental Protection Agency’s (EPA’s) toxic chemicals database revealed that, for a majority ...


Which Drugs Cause Cancer?, Andrew Knight, Jarrod Bailey, Jonathan Balcombe 2016 Animal Consultants International

Which Drugs Cause Cancer?, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jarrod Bailey, Ph.D.

Animal tests yield misleading results.


Cancerous Contradictions: The Mis-Regulation Of Human Carcinogens Based On Animal Data, Andrew Knight, Jarrod Bailey, Jonathan Balcombe 2016 Animal Consultants International

Cancerous Contradictions: The Mis-Regulation Of Human Carcinogens Based On Animal Data, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Jarrod Bailey, Ph.D.

The regulation of human exposures to potential carcinogens constitutes society’s most important use of animal carcinogenicity data. However, for environmental contaminants of greatest U.S. concern, we found that in most cases (58.1%; 93/160) the U.S. Environmental Protection Agency (EPA) considered the animal data inadequate to support a classification of probable human carcinogen or noncarcinogen.

The World Health Organisation’s International Agency for Research on Cancer (IARC) is a leading international authority on carcinogenicity assessments. For chemicals lacking human exposure data (the great majority), IARC classifications of identical chemicals were significantly more conservative than EPA classifications ...


The Future Of Teratology Research Is In Vitro, Jarrod Bailey, Andrew Knight, Jonathan Balcombe 2016 University of Newcastle-upon-Tyne

The Future Of Teratology Research Is In Vitro, Jarrod Bailey, Andrew Knight, Jonathan Balcombe

Jarrod Bailey, Ph.D.

Birth defects induced by maternal exposure to exogenous agents during pregnancy are preventable, if the agents themselves can be identified and avoided. Billions of dollars and manhours have been dedicated to animal-based discovery and characterisation methods over decades. We show here, via a comprehensive systematic review and analysis of this data, that these methods constitute questionable science and pose a hazard to humans. Mean positive and negative predictivities barely exceed 50%; discordance among the species used is substantial; reliable extrapolation from animal data to humans is impossible, and virtually all known human teratogens have so far been identified in spite ...


Temporal Resolution Of Misfolded Prion Protein Transport, Accumulation, Glial Activation, And Neuronal Death In The Retinas Of Mice Inoculated With Scrapie, M. Heather West Greenlee, Melissa Lind, Robyn Kokemuller, Najiba Mammadova, Naveen Kondru, Sireesha Manne, Jodi Smith, Anumantha Kanthasamy, Justin Greenlee 2016 Iowa State University

Temporal Resolution Of Misfolded Prion Protein Transport, Accumulation, Glial Activation, And Neuronal Death In The Retinas Of Mice Inoculated With Scrapie, M. Heather West Greenlee, Melissa Lind, Robyn Kokemuller, Najiba Mammadova, Naveen Kondru, Sireesha Manne, Jodi Smith, Anumantha Kanthasamy, Justin Greenlee

Biomedical Sciences Publications

Currently, there is a lack of pathological landmarks to describe the progression of prion disease in vivo. Our goal was to use an experimental model to determine the temporal relationship between the transport of misfolded prion protein (PrPSc) from the brain to the retina, the accumulation of PrPSc in the retina, the response of the surrounding retinal tissue, and loss of neurons. Retinal samples from mice inoculated with RML scrapie were collected at 30, 60, 90, 105, and 120 days post inoculation (dpi) or at the onset of clinical signs of disease (153 dpi). Retinal homogenates were tested ...


Carbon Dioxide For Euthanasia: Concerns Regarding Pain And Distress, With Special Reference To Mice And Rats, Kathleen Conlee, Martin Stephens, Andrew N. Rowan, Lesley A. King 2016 The Humane Society of the United States

Carbon Dioxide For Euthanasia: Concerns Regarding Pain And Distress, With Special Reference To Mice And Rats, Kathleen Conlee, Martin Stephens, Andrew N. Rowan, Lesley A. King

Martin Stephens, Ph.D.

Carbon dioxide (CO2) is the most commonly used agent for euthanasia of laboratory rodents, used on an estimated tens of millions of laboratory rodents per year worldwide, yet there is a growing body of evidence indicating that exposure to CO2 causes more than momentary pain and distress in these and other animals. We reviewed the available literature on the use of CO2 for euthanasia (as well as anaesthesia) and also informally canvassed laboratory animal personnel for their opinions regarding this topic. Our review addresses key issues such as CO2 flow rate and final concentration, presence of oxygen, and prefilled chambers ...


Addressing Distress And Pain In Animal Research: The Veterinary, Research, Societal, Regulatory And Ethical Contexts For Moving Forward, Kathleen Conlee, Martin Stephens, Andrew N. Rowan 2016 The Humane Society of the United States

Addressing Distress And Pain In Animal Research: The Veterinary, Research, Societal, Regulatory And Ethical Contexts For Moving Forward, Kathleen Conlee, Martin Stephens, Andrew N. Rowan

Martin Stephens, Ph.D.

While most people recognize that biomedical scientists are searching for knowledge that will improve the health of humans and animals, the image of someone deliberately causing harm to an animal in order to produce data that may lead to some future benefit has always prompted an uncomfortable reaction outside the laboratory. However, proponents of animal research have usually justified the practice by reference to greater benefits (new knowledge and medical treatments) over lesser costs (in animal suffering and death). Given that one of the costs of animal research is the suffering experienced by the animals, the goal of eliminating distress ...


Possibilities For Refinement And Reduction: Future Improvements Within Regulatory Testing, Martin L. Stephens, Kathleen Conlee, Gina Alvino, Andrew N. Rowan 2016 The Humane Society of the United States

Possibilities For Refinement And Reduction: Future Improvements Within Regulatory Testing, Martin L. Stephens, Kathleen Conlee, Gina Alvino, Andrew N. Rowan

Martin Stephens, Ph.D.

Approaches and challenges to refining and reducing animal use in regulatory testing are reviewed. Regulatory testing accounts for the majority of animals reported in the most painful and/or distressful categories in the United States and Canada. Refinements in testing, including the use of humane endpoints, are of increasing concern. Traditional approaches to reduction (e.g., improving experimental design) are being supplemented with complementary approaches, such as the use of tier testing to eliminate some chemicals prior to in vivo testing. Technological advances in telemetry and noninvasive techniques will help decrease either the demand for animals in testing or animal ...


Resolving Animal Distress And Pain: Principles And Examples Of Good Practice In Various Fields Of Research, Alicia Karas, Matthew C. Leach, Karl A. Andrutis, Kathleen Conlee, John P. Gluck, Andrew N. Rowan, Martin L. Stephens 2016 Tufts University

Resolving Animal Distress And Pain: Principles And Examples Of Good Practice In Various Fields Of Research, Alicia Karas, Matthew C. Leach, Karl A. Andrutis, Kathleen Conlee, John P. Gluck, Andrew N. Rowan, Martin L. Stephens

Martin Stephens, Ph.D.

Pain and distress are central topics in legislation, regulations, and standards regarding the use of animals in research. However, in practice, pain has received greatly increased attention in recent years, while attention to distress has lagged far behind, especially for distress that is not induced by pain. A contributing factor is that there is less information readily available on distress, including practical information on its recognition, assessment and alleviation. This chapter attempts to help fill that void by reversing the usual pattern and giving greater attention to distress than to pain. In addition, we also bypass the pain versus distress ...


The Three Rs: The Way Forward, Michael Balls, Alan M. Goldberg, Julia H. Fentem, Caren L. Broadhead, Rex L. Burch, Michael F.W. Festing, John M. Frazier, Coenraad F.M. Hendriksen, Margaret Jennings, Margot D.O. van der Kamp, David B. Morton, Andrew N. Rowan, Claire Russell, William M.S. Russell, Horst Spielman, Martin Stephens, William S. Stokes, Donald W. Straughan, James D. Yager, Joanne Zurlo, Bert F.M. van Zutphen 2016 European Centre for the Validation of Alternative Methods

The Three Rs: The Way Forward, Michael Balls, Alan M. Goldberg, Julia H. Fentem, Caren L. Broadhead, Rex L. Burch, Michael F.W. Festing, John M. Frazier, Coenraad F.M. Hendriksen, Margaret Jennings, Margot D.O. Van Der Kamp, David B. Morton, Andrew N. Rowan, Claire Russell, William M.S. Russell, Horst Spielman, Martin Stephens, William S. Stokes, Donald W. Straughan, James D. Yager, Joanne Zurlo, Bert F.M. Van Zutphen

Martin Stephens, Ph.D.

This is the report of the eleventh of a series of workshops organised by the European Centre for the Validation of Alternative Methods (ECVAM), which was established in 1991 by the European Commission. ECVAM's main goal, as defined in 1993 by its Scientific Advisory Committee, is to promote the scientific and regulatory acceptance of alternative methods which are of importance to the biosciences and which reduce, refine or replace the use of laboratory animals. One of the first priorities set by ECVAM was the implementation of procedures which would enable it to become well-informed about the state-of-the-art of non-animal ...


Unrelieved Pain And Distress In Animals: An Analysis Of Usda Data On Experimental Procedures, Martin Stephens, Philip Mendoza, Adrianna Weaver, Tamara Hamilton 2016 The Humane Society of the United States

Unrelieved Pain And Distress In Animals: An Analysis Of Usda Data On Experimental Procedures, Martin Stephens, Philip Mendoza, Adrianna Weaver, Tamara Hamilton

Martin Stephens, Ph.D.

Pain and distress are core issues in the field of animal experimentation and in the controversy that surrounds it. We sought to add to the empirical base of the literature on pain and distress by examining government data on experimental procedures that caused unrelieved pain and distress (UPAD) in animals. Of the species regulated by the U.S. Department of Agriculture (USDA), most of the approximately 100,000 animals subjected to UP AD during the year analyzed (1992) were guinea pigs and hamsters. Most of these animals were used in industry laboratories for various testing procedures, primarily vaccine potency testing ...


The Minimization Of Research Animal Distress And Pain: Conclusions And Recommendations, Kathleen Conlee, Martin Stephens, Andrew N. Rowan 2016 The Humane Society of the United States

The Minimization Of Research Animal Distress And Pain: Conclusions And Recommendations, Kathleen Conlee, Martin Stephens, Andrew N. Rowan

Martin Stephens, Ph.D.

While the attention given to preventing, assessing, and alleviating pain in research animals has increased noticeably in recent decades, much remains to be done both in terms of implementing best practices and conducting studies to answer outstanding questions. In contrast, the attention to distress (particularly non-pain induced distress) has shown no comparable increase. There are many reasons for this discrepancy, including the conceptual untidiness of the distress concept, the paucity of pharmacological treatments for distress, and perceived lack of regulatory emphasis on distress. These are challenges that need to be addressed and overcome. This book is intended to help meet ...


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