Research Methods in Life Sciences Commons^™

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

Experimentation Collection

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 …

International Regulatory Definitions Of Animal Distress In Animal Research And Animal Production – An Overview., Jon Richmond

Laws and Legislation Collection

Various systems already exist to judge animal welfare - of which distress can be one component - in the laboratory setting (see Hendriksen and Morton 1998). Many rely on nonspecific measures; that is they may be manifestations of a number of states, not all of them necessarily indicative of poor welfare. Certainly, there is already good provision for methods to recognise some of the commoner manifestations of distress, arguably they are sufficiently meaningful to categorise various distress states, though to my mind they are for the present still not suited for use as means of strictly quantifying the negative impact/suffering …

Measurement And Mitigation Of Laboratory Animal Distress Sources Of Distress In The Animal Laboratory, Larry Carbone

Laboratory Experiments Collection

Pain and distress differ, but overlap. For the purposes of this discussion, we will consider pain to involve nociceptive input of stimuli that are potentially tissue damaging, and that further include an unpleasant emotional component (Merskey and Bogduk 1994). Pain need not necessarily induce distress, as when an animal or human willingly undergoes some painful situation in order to achieve a desired reward. In that case, while the pain may be unpleasant, it is not so severe as to be intolerable. Likewise, there are many potential causes of distress that do not involve physical pain.

The Role Of Clinical Veterinary Medicine In The Assessment And Treatment Of Laboratory Animal Distress, V. Hampshire

Veterinary Science and Medicine Collection

It is doubtful that the scientific community will ever arrive at a consensus definition for distress as it may be attempted for the purposes of improving animal welfare in and across the myriad of research, testing and teaching facilities in the United States and throughout the minuet of protocols that exist for animals. The stakeholders in this attempt can however address most causes of physiologic distress by instituting time-honored veterinary and agrarian approaches to animal surveillance. In this manner, the majority of individuals who participate in responsible and humane animal care might be assuaged in that a condition of maximum …

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

Laboratory Experiments Collection

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 …

Trichostatin A Inhibits Corneal Haze In Vitro And In Vivo, Ajay Sharma, Maneesh M. Mehan, Sunilima Sinha, John W. Cowden, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

PURPOSE. Trichostatin A (TSA), a histone deacetylase inhibitor, has been shown to suppress TGF- –induced fibrogenesis in many nonocular tissues. The authors evaluated TSA cytotoxicity and its antifibrogenic activity on TGF- –driven fibrosis in the cornea with the use of in vitro and in vivo models.

METHODS. Human corneal fibroblasts (HSFs) were used for in vitro studies, and New Zealand White rabbits were used for in vivo studies. Haze in the rabbit cornea was produced with photorefractive keratectomy (PRK) using excimer laser. Trypan blue exclusion and MTT assays evaluated TSA cytotoxicity to the cornea. Density of haze in the rabbit …

Letter From The Dean, Lalit Verma

Discovery, The Student Journal of Dale Bumpers College of Agricultural, Food and Life Sciences

No abstract provided.

Unintended Facilitation Between Marine Consumers Generates Enhanced Mortality For Their Shared Prey, F. Joel Fodrie, Matthew D. Kenworthy, Sean P. Powers

University Faculty and Staff Publications

We manipulated predator densities and prey vulnerability to explore how interactions between two predators affect overall mortality of their shared prey. Our threemember study system included eastern oysters (Crassostrea virginica) and two of its major consumers: southern oyster drills (Stramonita haemastoma) and stone crabs (Menippe adina). Field experiments demonstrated that drills and crabs foraging together generated higher than expected oyster mortality based on each species operating independently, even though crabs also killed some drills. In subsequent laboratory trials, we experimentally mimicked the handling of oysters by foraging crabs and confirmed that crabs facilitated drills by breeching oyster valves, thereby granting …

Reviewing Existing Knowledge Prior To Conducting Animal Studies, Andrew Knight

Experimentation Collection

Highly polarised viewpoints about animal experimentation have often prevented agreement. However, important common ground between advocates and opponents was demonstrated within a discussion forum hosted at www.research-methodology.org.uk in July–August 2008, by the independent charity, SABRE Research UK. Agreement existed that many animal studies have methodological flaws — such as inappropriate sample sizes, lack of randomised treatments, and unblinded outcome assessments — that may introduce bias and limit statistical validity. There was also agreement that systematic reviews of the human utility of animal models yield the highest quality of evidence, as their reliance on methodical and impartial methods to select significant …

Developmental Toxicity Testing: Protecting Future Generations?, Jarrod Bailey

Experimentation Collection

A recent editorial is discussed, which implied that animal-based developmental and reproductive toxicology tests will continue to be crucial, that the thalidomide disaster could have been prevented by more animal testing, and that tests on juvenile animals would help to protect children (as developing adults) from the adverse effects of pharmaceuticals. It is argued that animal tests in these scientific areas do not provide reliable data that are predictive for human responses and, even if they did, the tests are too expensive and time-consuming for application to the very large number of substances that need to be tested. It is …

Arkansas Animal Science Department Report 2008, Zelpha B. Johnson, D. Wayne Kellogg

Arkansas Agricultural Experiment Station Research Series

No abstract provided.

An Assessment Of The Role Of Chimpanzees In Aids Vaccine Research, Jarrod Bailey

Laboratory Experiments Collection

Prior to Simian Immunodeficiency Virus (SIV)-infected macaques becoming the ‘model of choice’ in the 1990s, chimpanzees were widely used in AIDS vaccine research and testing. Faced with the continued failure to develop an effective human vaccine, some scientists are calling for a return to their widespread use. To assess the past and potential future contribution of chimpanzees to AIDS vaccine development, databases and published literature were systematically searched to compare the results of AIDS vaccine trials in chimpanzees with those of human clinical trials, and to determine whether the chimpanzee trials were predictive of the human response. Protective and/or therapeutic …

Anti-Inflammatory Effects Of Ppar-Gamma In Surgical Brain Injury (Sbi), Amy Hyong

Loma Linda University Electronic Theses, Dissertations & Projects

Introduction: Brain injury can be caused by neurosurgical procedures themselves, due to direct trauma, retractor stretch, intraoperative hemorrhage and electrocautery damage. As a result of this surgical brain injury (SBI) postoperative complications such as inflammation, brain edema, and cell death can occur in the susceptible brain areas. Cerebral inflammation is a known contributor to the pathophysiology of brain injury. Following brain injury, the release of inflammatory mediators facilitates the development of BBB breakdown, cerebral edema, oxidative stress and neuronal death, resulting in further tissue damage in the brain and poor neurological outcomes. This study evaluates whether the use of a …

Estimates For Worldwide Laboratory Animal Use In 2005, Katy Taylor, Nicky Gordon, Gill Langley, Wendy Higgins

Laboratory Experiments Collection

Animal experimentation continues to generate public and political concern worldwide. Relatively few countries collate and publish animal use statistics, yet this is a first and essential step toward public accountability and an informed debate, as well as being important for effective policy-making and regulation. The implementation of the Three Rs (replacement, reduction and refinement of animal experiments) should be expected to result in a decline in animal use, but without regular, accurate statistics, this cannot be monitored. Recent estimates of worldwide annual laboratory animal use are imprecise and unsubstantiated, ranging from 28–100 million. We collated data for 37 countries that …

The Beginning Of The End For Chimpanzee Experiments?, Andrew Knight

Experimentation Collection

The advanced sensory, psychological and social abilities of chimpanzees confer upon them a profound ability to suffer when born into unnatural captive environments, or captured from the wild – as many older research chimpanzees once were – and when subsequently subjected to confinement, social disruption, and involuntary participation in potentially harmful biomedical research. Justifications for such research depend primarily on the important contributions advocates claim it has made toward medical advancements. However, a recent large-scale systematic review indicates that invasive chimpanzee experiments rarely provide benefits in excess of their profound animal welfare, bioethical and financial costs. The approval of large …

Neuronal Connections From The Cervix To The Spinal Cord Before Parturition, Mary Medina Groves

Loma Linda University Electronic Theses, Dissertations & Projects

By the day before birth, the density of nerve fibers in the cervix has increased compared to earlier in pregnancy or in nonpregnant mice. Similar findings are reported in parturient women. To test the hypothesis that connections between the cervix and spinal cord are enhanced by term, the cervix of nonpregnant and time-dated pregnant mice (day 15 or 18 post-breeding) was injected with pseudorabies virus (PRV), a trans-synaptic retrograde neural tract tracer. Mice were euthanized and perfused 5 days later. The spinal cord and cervix were removed and postfixed overnight, immersed in sucrose, and cryostat sections through the thoracic to …

Mechanisms Of T Helper Cell Modulation In A Simulated Space Radiation Environment, Asma Rizvi

Loma Linda University Electronic Theses, Dissertations & Projects

Exposure to solar particle events (SPEs) poses the most serious threat to astronaut health. Due to this radiation environment, exploration of the solar system beyond Earth’s orbit entails many risks for the crew on these deep space missions. Depression or dysfunction of the immune system is a major concern due to its high radio-sensitivity; potential consequences include overwhelming infection, development of cancer, fibrosis, and poor wound healing. Astronauts are also exposed to low dose/low dose rate (LDR) radiation. A three month stay at the international space station exposes them to ~ 0.05 Gy of radiation.

C57BL/6 mice received LDR gamma-radiation …

Systematic Reviews Of Animal Experiments Demonstrate Poor Contributions To Human Healthcare, Andrew Knight

Experimentation Collection

Widespread reliance on animal models during preclinical research and toxicity testing assumes their reasonable predictivity for human outcomes. However, of 20 published systematic reviews examining human clinical utility located during a comprehensive literature search, animal models demonstrated significant potential to contribute toward clinical interventions in only two cases, one of which was contentious. Included were experiments expected by ethics committees to lead to medical advances, highly-cited experiments published in major journals, and chimpanzee experiments—the species most generally predictive of human outcomes. Seven additional reviews failed to demonstrate utility in reliably predicting human toxicological outcomes such as carcinogenicity and teratogenicity. Results …

Medical Progress Depends On Animal Models - Doesn't It?, Robert A. J. Matthews

Validation of Animal Experimentation Collection

Animal models are widely recognized as being essential to the progress of medical science. In countering the critics’ arguments of the use of animals in medicine, one statement has acquired almost talismanic importance:

‘Virtually every medical achievement of the last century has depended directly or indirectly on research with animals.’

In this essay, the origins and justification of this oft-repeated statement are examined. Despite its endorsement by leading academic bodies, it is far from clear that the statement has been, or even could be, formally validated.

Mammals Of Nebraska: Checklist, Key, And Bibliography, Hugh H. Genoways, Justin D. Hoffman, Patricia Freeman, Kenneth N. Geluso, Russell A. Benedict, Jeffrey J Huebschman

University of Nebraska State Museum: Staff and Affiliates, Publications

The Recent mammalian fauna of Nebraska is composed of 89 native species, 8 domestic species that can have feral populations, and 4 wild species introduced by humans, but not by intentional action. Thus, the included checklist and dichotomous key contain 101 species of mammals. Of the native species, 36 are rodents, 20 carnivores, 13 bats, 7 shrews and mole, 7 even-toed ungulates, 4 rabbits and hares, 1 armadillo, and 1 opossum. Another 8 species are identified as potentially occurring in peripheral areas of Nebraska. The bibliography includes 1693 entries that each contain data concerning one or more species of mammals …

Non-Animal Methodologies Within Biomedical Research And Toxicity Testing, Andrew Knight

Experimentation Collection

Laboratory animal models are limited by scientific constraints on human applicability, and increasing regulatory restrictions, driven by social concerns. Reliance on laboratory animals also incurs marked – and in some cases, prohibitive – logistical challenges, within high-throughput chemical testing programmes, such as those currently underway within Europe and the US. However, a range of non-animal methodologies is available within biomedical research and toxicity testing. These include: mechanisms to enhance the sharing and assessment of existing data prior to conducting further studies, and physicochemical evaluation and computerised modelling, including the use of structure-activity relationships and expert systems. Minimally-sentient animals from lower …

Impact Of Stressing A Pen Mate On Physiological Responses Of Growing Pigs, Brent Koonce, Elizabeth B. Kegley, Doug Galloway, Jason Apple

Discovery, The Student Journal of Dale Bumpers College of Agricultural, Food and Life Sciences

Crossbred barrows and gilts (n = 36), weighing 16.59 ± 2.1 kg, were used to test the effects of stressing a pen mate on the physiological responses of growing pigs. Pigs were randomly allotted to 6 groups after stratifying according to gender, litter origin, and body weight. Dominance order was determined within each group, and 1 to 3 d prior to the stress treatment the most- and least-dominant pigs within a group were fitted with indwelling catheters in their vena cavas. Over 3 d, groups were either: 1) isolated from audile and visual contact with stressed pigs in a separate …

Investigating Current Efficacies Of Several Nematocides For Use In Cattle According To The Fecal Egg Count Reduction Test, Tifanie Silver, Chris Tucker, Jeremy Powell, Jana Reynolds, Zelpha Johnson, Bill Lindsey, Pete Hornsby, T. A. Yazwinski

Discovery, The Student Journal of Dale Bumpers College of Agricultural, Food and Life Sciences

Utilizing small groups of naturally infected replacement heifers, fecal egg count reduction tests (FECRT) were conducted in the later months of 2007 at the University of Arkansas Savoy Research Station. Each test was 28 d in length, consisting of individual fecal nematode egg counts (EPG) and coprocultures. For the first test, the calves were ranked by beginning EPG, blocked, and randomly assigned treatment within each block. Nine to ten animals were in each treatment group. In this test, neither IVOMEC (® Merial) or IVERMECTIN (® Durvet), both delivered as an injectable at the rate of 0.2 mg of ivermectin kg-1 …

Systematic Reviews Of Animal Experiments Demonstrate Poor Human Clinical And Toxicological Utility, Andrew Knight

Experimentation Collection

The assumption that animal models are reasonably predictive of human outcomes provides the basis for their widespread use in toxicity testing and in biomedical research aimed at developing cures for human diseases. To investigate the validity of this assumption, the comprehensive Scopus biomedical bibliographic databases were searched for published systematic reviews of the human clinical or toxicological utility of animal experiments. In 20 reviews in which clinical utility was examined, the authors concluded that animal models were either significantly useful in contributing to the development of clinical interventions, or were substantially consistent with clinical outcomes, in only two cases, one …

Considerations For Determining Optimal Mouse Caging Density, Charmaine Foltz, Larry Carbone, David Delong, Bernard E. Rollin, Pascalle Van Loo, Julia Whitaker, Axel Wolff

Laboratory Research and Animal Welfare Collection

At the 2006 National Meeting of the American Association of Laboratory Animal Science, a panel discussed the question of what constitutes optimal or acceptable housing density for mice. Though there is a consensus that present guidelines are somewhat arbitrarily defined, scientific research has not yet been able to provide clear recommendations for amending them. Speakers explored the many factors that influence decisions on mouse housing, including regulatory requirements, scientific data and their interpretation, financial considerations and ethical concerns. The panel largely agreed that animal well-being should be the measure of interest in evaluating housing density and that well-being includes not …

The Development Of New Concepts For Assessing Reproductive Toxicity Applicable To Large Scale Toxicological Programmes, S. Bremer, C. Pellizzer, S. Hoffmann, T. Seidle, T. Hartung

Experimentation Collection

Large scale toxicological testing programmes which are currently ongoing such as the new European chemical legislation REACH require the development of new integrated testing strategies rather than applying traditional testing schemes to thousands of chemicals. The current practice of requiring in vivo testing for every possible adverse effect endanger the success of these programmes due (i) to limited testing facilities and sufficient capacity of scientific/technical knowledge for reproductive toxicity; (ii) an unacceptable number of laboratory animals involved (iii) an intolerable number of chemicals classified as false positive.

A key aspect of the implementation of new testing strategies is the determination …

Animal Research: A Moral Science, Bernard E. Rollin

Experimentation Collection

No abstract provided.

The Effect Of Radiation And Repeated Sub-Culturing On Tgf-Β1 Signaling In Frtl-5 Cells, Cheryl G. Burrell

Loma Linda University Electronic Theses, Dissertations & Projects

From our ongoing in vitro studies using the Fisher Rat Thyroid cell line-5 (FRTL-5) we recorded accelerated growth, reduced follicularization and reduction in thyroxin release that occurred as the cells were repeatedly sub-cultured. We also recorded that these changes occurred earlier and more rapidly following radiation exposure. We determined that TGF-β1 production increased under both conditions. We hypothesized that alteration in the TGF-β1 signaling pathway contributed to the changes observed in the cellular properties of FRTL-5 cells. Our objective was to examine some of the players in the TGF-β1 signaling pathway to determine whether radiation and/or repeated subculturing promoted changes …

Radiation-Induced Increases In Pkc Modulate Integrin Expression And Contribute To Fibrotic Changes, Pinal Rushikesh Pandya

Loma Linda University Electronic Theses, Dissertations & Projects

The sequences of events in fibrosis are similar to those in wound healing; however, the normal termination and resolution stages do not take place. The initial cellular response following ionizing radiation involves accumulation of the ECM (extracellular matrix) including collagen, fibronectin and the interaction of many growth factors (cytokines) with their receptors. There are a number of unanswered questions regarding many aspects of radiation-induced fibrosis, including the initial triggers and physical changes that initiate the process. We have confirmed that elevated pKC and other cellular changes following radiation are similar to those found at sites of inflammation. This information leads …

Maturational Changes In Cerebrovascular Thick- And Thin-Filament Regulation, Renan Joel Sandoval

Loma Linda University Electronic Theses, Dissertations & Projects

The present study focused on the main hypothesis that age-related changes in myofilament Ca²⁺ sensitivity involve simultaneous changes in the relations between cytosolic Ca²⁺ transients, myosin phosphorylation, and force development. To define the effects of late fetal and early postnatal maturation, parallel experiments were carried out using cerebral arteries from both term lamb fetuses (140-141 days of gestation) and nonpregnant adult sheep. Fetal and adult cerebral arteries were stimulated by either mechanically, electromechanically, and/or pharmacomechanically-induced contractions, and the relations of cytosolic Ca²⁺, MLC phosphorylation, and contractile tensions were measured. These measurements allowed for stimulus and age-dependent …