Medicine and Health Sciences Commons^™

Autonomic Nervous System Reactivity In A Free-Ranging Mammal: Effects Of Dominance Rank And Personality, Elodie F. Briefer, James A. Oxley, Alan G. Mcelligott

Elodie Briefer, PhD

Modulation of the autonomic nervous system (ANS) activity allows animals to effectively respond to internal and external stimuli in everyday challenges via changes in, for example, heart and respiration rate. Various factors, ranging from social such as dominance rank to internal such as personality or affective states can impact animal physiology. Our knowledge of the combinatory effects of social and internal factors on ANS basal activity and reactivity, and of the importance that each factor has in determining physiological parameters, is limited, particularly in nonhuman, free-ranging animals. In this study, we tested the effects of dominance rank and personality (assessed …

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

Jarrod Bailey, PhD

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 …

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

Jarrod Bailey, PhD

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 of the …

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

Jarrod Bailey, PhD

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 128 chemicals with human or …

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

Jarrod Bailey, PhD

Animal tests yield misleading results.

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

Jarrod Bailey, PhD

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 (p

Long-Term Effects Of Early Social Isolation In Macaca Mulatta: Changes In Dopamine Receptor Function Following Apomorphine Challenge, Mark H. Lewis, John P. Gluck, Tom L. Beauchamp, Michael F. Keresztury, Richard B. Mailman

John P. Gluck, PhD

The hypothesis that early social isolation results in long-term alterations in dopamine receptor sensitivity was tested using older adult rhesus monkeys. Isolated and control monkeys were challenged with apomorphine (0.1 and 0.3 mg/kg), and the drug effects on spontaneous blink rate, stereotyped behavior, and self-injurious behavior were quantified using observational measures. Monoamine metabolites were quantified from cisternal CSF by HPLC-EC, prior to pharmacological challenge. Isolated and control monkeys did not differ in CSF concentrations of HVA, 5-HIAA, or MHPG. At the higher dose, apomorphine significantly increased the rate of blinking, the occurrence of whole-body stereotypies, and the intensity of stereotyped …

Social Deprivation Of Infant Rhesus Monkeys Alters The Chemoarchitecture Of The Brain: I. Subcortical Regions, Lee J. Martin, Dawn M. Spicer, Mark H. Lewis, John P. Gluck, Linda C. Cork

John P. Gluck, PhD

Rhesus monkeys (Macaca mulatta) reared during the first year of life without social contact develop persistent stereotyped movements, self-directed behaviors, and psychosocial abnormalities, but neurobiological mechanisms underlying the behaviors of socially deprived (SD) monkeys are unknown. Monkeys were reared in total social deprivation for the first 9 months of life; control monkeys were reared socially (SR) with mothers and peers. Subjects were killed at 19-24 yr of age. Because the behaviors of SD monkeys are reminiscent of changes in striatal or amygdalar function, we used immunocytochemistry for substance P (SP), leutine-enkephalin (LENK), somatostatin, calbindin, and tyrosine hydroxylase (TH) to evaluate …

Noncompliance With Public Health Service (Phs) Policy On Humane Care And Use Of Laboratory Animals: An Exploratory Analysis, Leah M. Gomez, Kathleen Conlee, Martin Stephens

Martin Stephens, PhD

The National Institutes of Health (NIH) is a major biomedical research-funding body in the United States. Approximately 40% of NIH-funded research involves experimentation on nonhuman animals (Monastersky, 2008). Institutions that conduct animal research with NIH funds must adhere to the Public Health Service (PHS) care and use standards of the Office of Laboratory Animal Welfare (OLAW, 2002a). Institutions deviating significantly from the PHS’s animal care and use standards must report these incidents to the NIH’s OLAW. This study is an exploratory analysis of all the significant deviations reported by animal-research facilities to OLAW during a 3-month period. The study identifies …

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, PhD

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 …

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

Martin Stephens, PhD

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 …

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, PhD

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 Science Of Sentience Is Reshaping How We Think About Animals, Debra Durham

Debra Durham, PhD

Broom’s Sentience and Animal Welfare (2014) provides its readers with an excellent overview of the evolving role of sentience in our understanding animal welfare as well as insights into why sentience matters for practice and policy.

Recognition Of Distress In Animals – A Philosophical Prolegomenon, Bernard E. Rollin

Bernard Rollin, PhD

For those who continue to doubt the studiability of distress or suffering or misery in all of its forms in animals, consider the following thought experiment: If the government were to come up with a billion dollars in research funding for animal distress, would that money go a-begging? We can study these states just as we studied pain—excellent work on boredom by Franciose Wemelsfelder in a volume on laboratory animal welfare I co-edited made the methodology for such study quite explicit. (Wemelsfelder, 1990) And when the ideological scales fall from our eyes, we realize that the work of scientists like …

Ethics And Euthanasia, Bernard E. Rollin

Bernard Rollin, PhD

No abstract provided.

Microhabitat Use Affects Brain Size And Structure In Intertidal Gobies, Gemma E. White, Culum Brown

Culum Brown, PhD

The ecological cognition hypothesis poses that the brains and behaviours of individuals are largely shaped by the environments in which they live and the associated challenges they must overcome during their lives. Here we examine the effect of environmental complexity on relative brain size in 4 species of intertidal gobies from differing habitats. Two species were rock pool specialists that lived on spatially complex rocky shores, while the remainder lived on dynamic, but structurally simple, sandy shores. We found that rock pool-dwelling species had relatively larger brains and telencephalons in particular, while sand-dwelling species had a larger optic tectum and …

Variation In Brain Morphology Of Intertidal Gobies: A Comparison Of Methodologies Used To Quantitatively Assess Brain Volumes In Fish, Gemma E. White, Culum Brown

Culum Brown, PhD

When correlating brain size and structure with behavioural and environmental characteristics, a range of techniques can be utilised. This study used gobiid fishes to quantitatively compare brain volumes obtained via three different methods; these included the commonly used techniques of histology and approximating brain volume to an idealised ellipsoid, and the recently established technique of X-ray micro-computed tomography (micro-CT). It was found that all three methods differed significantly from one another in their volume estimates for most brain lobes. The ellipsoid method was prone to over- or under-estimation of lobe size, histology caused shrinkage in the telencephalon, and although micro-CT …

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

Andrew Knight, 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

Andrew Knight, PhD

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 (p

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

Andrew Knight, PhD

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 …

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

Andrew Knight, PhD

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 of the …

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

Andrew Knight, 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 128 chemicals with human or …

Variation In Avian Pathogenic Escherichia Coli Colonization Levels In Chickens, Melissa Monson, Michael Kaiser, Susan Lamont

Melissa Monson

Colonization levels in five tissues after avian pathogenic Escherichia coli (APEC) inoculation were investigated in chickens to generate phenotypic data for a genome wide association study (GWAS). Bacterial loads were measured in 370 birds and varied among individuals and tissues. Mean bacterial levels were significantly different between tissues (right lung > spleen > left lung and liver > blood). There were also significant correlations in bacterial load between tissues. These data suggest that colonization levels could be used as phenotypes in GWAS and could help identify markers associated with poultry resistance to APEC infections. After verification, these markers could be used for genetic …

Association Of Different Iowa Livestock Truck Wash Stations Service Levels With Enterobacteriaceae Counts, Amber Danielson, Samaneh Azarpajouh, Anna Johnson, James Dickson, Locke Karriker, Rodney Baker, Christopher Rademacher, Troy Bigelow, Kenneth Stalder

Samaneh Azarpajouh

Data from eighteen different truck washes were used to compare the association of different service levels with Enterobacteriaceae counts. Service levels were classified into three different categories; prewash (n=78), post wash with disinfectant (n=78), and post wash without disinfectant (n=12). A total of 168 drag swabs were used for collection for the purpose of this study. Prewash services were defined as trailers before they were scraped out and washed. Post wash with or without disinfectant services were defined as after the trailers were washed and disinfectant was or was not applied. Prewash trailers tended to have higher Enterobacteriaceae counts of …

Investigation Of Swine Dysentery Associated With "Brachyspira Hampsonii" Strain Eb107 And Comparison Of Diagnostic Methods, Bailey Lauren Wilberts

Bailey (Wilberts) Arruda

Swine dysentery (SD) is an important cause of mucohemorrhagic diarrhea in pigs. Swine dysentery is associated with infection by Brachyspira hyodysenteriae which has historically been the only recognized strongly beta-hemolytic Brachyspira sp. However, in recent years, not all strongly beta-hemolytic isolates have been identified as B. hyodysenteriae using PCR assays specific for this species. Several reports have described putatively novel strongly beta-hemolytic Brachyspira spp. including "Brachyspira hampsonii" associated with SD. A pig inoculation study was used to compare lesions and colonic mucin expression associated with infection by B. hyodysenteriae or "B. hampsonii." Diagnosis of SD commonly …

Raav2/5 Gene-Targeting To Rods: Dose-Dependent Efficiency And Complications Associated With Different Promoters, William Beltran, Sanford L. Boye, Shannon E. Boye, Vince A. Chiodo, Alfred S. Lewin, William W. Hauswirth, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

A prerequisite for using corrective gene therapy to treat humans with inherited retinal degenerative diseases that primarily affect rods is to develop viral vectors that target specifically this population of photoreceptors. The delivery of a viral vector with photoreceptor tropism coupled with a rod-specific promoter is likely to be the safest and most efficient approach to target expression of the therapeutic gene to rods. Three promoters that included a fragment of the proximal mouse opsin promoter (mOP), the human G-protein-coupled receptor protein kinase 1 promoter (hGRK1), or the cytomegalovirus immediate early enhancer combined with the chicken β actin proximal promoter …

Window Into Retinal Studies, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

Professor Gustavo Aguirre discusses the context of his research studies at the University of Pennsylvania, which are currently concentrating on the degenerative disease, retinitis pigmentosa.

Photoreceptor Dysplasia: An Inherited Progressive Retinal Atrophy Of Miniature Schnauzer Dogs, Charles J. Parshall, Milton Wyman, Susan Nitroy, Gregory M. Acland, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

A progressive retinal atrophy (PRA) affecting Miniature Schnauzer dogs is reported. Of the 287 individuals (148 female, 139 male) comprising the study population, 66 (23 percent) were affected (33 female, 33 male) and 221 animals (115 female, 106 male) were phenotypically normal. There was no sex predilection for the disease. Results of histologic and electroretinographic studies indicate that the disease is a new and different type of PRA, characterized by unique morphologic and functional deficits during rod and cone development. Accordingly, the disease has been termed photoreceptor dysplasia. Clinically, and particularly ophthalmoscopically, diagnosis is only practicable in very late stages …

Drug Delivery To Posterior Intraocular Tissues: Third Annual Arvo/Pfizer Ophthalmics Research Institute Conference, Henry F. Edelhauser, Jeffrey H. Boatright, John M. Nickerson, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

The third Annual ARVO/Pfizer Ophthalmic Research Institute Conference was held Friday and Saturday, May 4 and 5, 2007 at the Fort Lauderdale Grande Hotel and Yacht Club, Fort Lauderdale, Florida. The conference, funded by the ARVO Foundation for Eye Research through a grant from Pfizer Ophthalmics, provided an opportunity to gather experts from within and outside ophthalmology to develop strategies to address drug delivery to posterior intraocular tissues—a topic of great interest, as the major route of drug delivery is via intravitreous injection.

Identification Of Genetic Variation And Haplotype Structure Of The Canine Abca4 Gene For Retinal Disease Association Studies, Barbara Zangerl, Sarah J. Lindauer, Gregory M. Acland, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

Over 200 mutations in the retina specific member of the ATP-binding cassette transporter superfamily (ABCA4) have been associated with a diverse group of human retinal diseases. The disease mechanisms, and genotype–phenotype associations, nonetheless, remain elusive in many cases. As orthologous genes are commonly mutated in canine models of human blinding disorders, canine ABCA4 appears to be an ideal candidate gene to identify and study sequence changes in dogs affected by various forms of inherited retinal degeneration. However, the size of the gene and lack of haplotype assignment significantly limit targeted association and/or linkage approaches. This study assessed the naturally observed …