Research Methods in Life Sciences Commons^™

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 …

Iron Dysregulation And Inflammation In Alzheimer’S Disease, Shino D. Magaki

Loma Linda University Electronic Theses, Dissertations & Projects

Alzheimer’s disease (AD) is the most common form of senile dementia in the US and worldwide but the causes of its pathogenesis are currently unknown. In this study, we examined two processes that have been implicated in the early stages of AD and other forms of neurodegeneration, iron dysregulation and inflammation, both of which can promote the increased production of amyloid precursor protein (APP). We have measured different pools of brain iron in transgenic iron regulatory protein 2 knockout (IRP2-/-) mice in the early stages of neurodegeneration and in affected brain regions from AD patients at different stages of the …

A Holistic Approach To Taking Research Animal Suffering Seriously, Martin Stephens, Kathleen Conlee

Experimentation Collection

It is widely agreed, and often legally required, that distress and pain in research animals should be minimized--for the sake of animal welfare, ethical obligation, and public concern, as well as scientific quality. As testimony to the importance of distress and pain to stakeholders interested in research animals, many countries compile and publish annual statistics documenting overall patterns and trends on distress and pain in research animals.

We argue for a holistic approach to minimizing research animal suffering, with all relevant parties sharing in this responsibility. Researchers, laboratory personnel, oversight committees, and facility administrators are central to day-to-day animal care. …

Of Mice And Men, Bernard E. Rollin

Experimentation Collection

No abstract provided.

Chimpanzee Research: An Examination Of Its Contribution To Biomedical Knowledge And Efficacy In Combating Human Diseases, Jarrod Bailey, Jonathan Balcombe, Theodora Capaldo

Experimentation Collection

Research on captive chimpanzees incurs considerable animal welfare, ethical and financial costs. Advocates of such research claim these costs are outweighed by substantial advancements in biomedical knowledge, and that the genetic similarity of chimpanzees to humans enables the former to make critical contributions to preventing, diagnosing and combating human diseases. To assess these claims, we examined the disciplines investigated in 749 studies of captive chimpanzees published from 1995-2004 inclusive, and subjected 95 randomly selected papers to a detailed citation analysis:

49.5% (47/95) of papers had not been cited at the time of this study; 38.5% (34/95) were cited by 116 …

Arkansas Animal Science Department Report 2006, Zelpha B. Johnson, D. Wayne Kellogg

Arkansas Agricultural Experiment Station Research Series

No abstract provided.

Report Of The Working Group On Animal Distress In The Laboratory, Marilyn Brown, Larry Carbone, Kathleen Conlee, Marian Dawkins, Ian J. Duncan, David Fraser, Gilly Griffin, Victoria A. Hampshire, Lesley A. Lambert, Joy A. Mench, David Morton, Jon Richmond, Bernard E. Rollin, Andrew N. Rowan, Martin L. Stephens, Hanno Würbel

Laboratory Experiments Collection

Finding ways to minimize pain and distress in research animals is a continuing goal in the laboratory animal research field. Pain and distress, however, are not synonymous, and often measures that alleviate one do not affect the other. Here, the authors provide a summary of a meeting held in February 2004 that focused on distress in laboratory animals. They discuss the difficulties associated with defining ‘distress,’ propose methods to aid in recognizing and alleviating distressful conditions, and provide recommendations for animal research conduct and oversight that would minimize distress experienced by laboratory animals.

In Vitro Antimicrobial Efficacy Of Calcium Hydroxides In Root Dentin, Josef W. Lubisich

Loma Linda University Electronic Theses, Dissertations & Projects

Enterococcus faecalis is the most commonly isolated bacteria in failed root canal treatment. Endodontic intracanal medicaments are commonly tested using standardized bovine cylinders infected with bacteria. The literature is not clear on whether calcium hydroxides are able to remove E. faecalis from the dentinal tubules. One reason for this is that there are several varying forms of calcium hydroxide commonly used. The purpose of the present experiment was to determine whether four commonly used calcium hydroxide products were able to reduce E. faecalis from four incremental samples of dentin and to determine if there was a statistically significant difference between …

Effects Of Diabetes Mellitus On The Healing Of The Dental Pulp, Stuart Evan Garber

Loma Linda University Electronic Theses, Dissertations & Projects

Diabetes Mellitus (DM) has been implicated as a factor affecting healing. The purpose of this study was to use the healing of experimentally exposed pulps subsequent to pulp capping as a model to determine the effect of DM on healing.

Twenty-two Sprague-Dawley rats were divided into two groups of eleven animals each. In one group, DM was induced by injection of 70 mg/KG of streptozotocin. In the other group, the animals were injected with sterile saline. Under anesthesia with Ketamine and Xylazine, the pulps of the maxillary first molars of all rats were exposed using a 1/16 round bur under …

The Effect Of Calcium Hydroxide Pastes On Root Dentin Fracture Resistance, Kurt W. Sturz

Loma Linda University Electronic Theses, Dissertations & Projects

Calcium hydroxide is a common intracanal medicament used in the treatment of immature teeth that have been subjected to trauma or decay prior to root canal therapy. The effect of calcium hydroxide on immature root dentin is important. One area of concern is the effect that calcium hydroxide has on the fracture resistance of an immature tooth. It is the aim of this study to compare the effect of four different commercially available calcium hydroxide pastes on the fracture resistance of bovine teeth. Seventy-five freshly extracted, intact bovine incisors were prepared according to a modified Haapasalo and Orstavik technique. Each …

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

Experimentation Collection

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

Experimentation Collection

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 …

Animal Carcinogenicity Studies: 2. Obstacles To Extrapolation Of Data To Humans, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Experimentation Collection

Due to limited human exposure data, risk classification and the consequent regulation of exposure to potential carcinogens has conventionally relied mainly upon animal tests. However, several investigations have revealed animal carcinogenicity data to be lacking in human predictivity. To investigate the reasons for this, we surveyed 160 chemicals possessing animal but not human exposure data within the US Environmental Protection Agency chemicals database, but which had received human carcinogenicity assessments by 1 January 2004. We discovered the use of a wide variety of species, with rodents predominating, and of a wide variety of routes of administration, and that there were …

Animal Carcinogenicity Studies: 3. Alternatives To The Bioassay, Andrew Knight, Jarrod Bailey, Jonathan Balcombe

Experimentation Collection

Conventional animal carcinogenicity tests take around three years to design, conduct and interpret. Consequently, only a tiny fraction of the thousands of industrial chemicals currently in use have been tested for carcinogenicity. Despite the costs of hundreds of millions of dollars and millions of skilled personnel hours, as well as millions of animal lives, several investigations have revealed that animal carcinogenicity data lack human specificity (i.e. the ability to identify human non-carcinogens), which severely limits the human predictivity of the bioassay. This is due to the scientific inadequacies of many carcinogenicity bioassays, and numerous serious biological obstacles, which render profoundly …

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

Experimentation Collection

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

Stromal Haze, Myofibroblasts, And Surface Irregularity After Prk, Marcelo V. Netto, Rajiv R. Mohan, Sunilima Sinha, Ajay Sharma, William Dupps, Steven E. Wilson

Pharmacy Faculty Articles and Research

The aim of this study was to investigate the relationship between the level of stromal surface irregularity after photorefractive keratectomy (PRK) and myofibroblast generation along with the development of corneal haze.

Variable levels of stromal surface irregularity were generated in rabbit corneas by positioning a fine mesh screen in the path of excimer laser during ablation for a variable percentage of the terminal pulses of the treatment for myopia that does not otherwise generate significant opacity. Ninety-six rabbits were divided into eight groups[.]

Slit lamp analysis and haze grading were performed in all groups. Rabbits were sacrificed at 4 hr …

Effect Of Prophylactic And Therapeutic Mitomycin C On Corneal Apoptosis, Cellular Proliferation, Haze, And Long-Term Keratocyte Density In Rabbits, Marcelo V. Netto, Rajiv R. Mohan, Sunilima Sinha, Ajay Sharma, Pankaj C. Gupta, Steven E. Wilson

Pharmacy Faculty Articles and Research

PURPOSE—To determine the mechanism through which topical mitomycin C prevents and treats corneal haze after photorefractive keratectomy (PRK) and to examine the effects of dosage and duration of exposure.

METHODS—In 224 New Zealand rabbits, −9.0 diopter PRK with mitomycin C or balanced salt solution was performed. Haze level was graded at the slit-lamp. Rabbits were sacrificed at 4 hours, 24 hours, 4 weeks, or 6 months after surgery and immunohistochemistry was performed with TUNEL assay, Ki67 and α-SMA.

RESULTS—TUNEL-positive apoptotic cells marginally increased in all mitomycin C groups whereas Ki67-positive mitotic cells decreased significantly following mitomycin C application. A greater …

Mechanisms Of Hbo-Induced Neuroprotection In A Neonatal Hypoxia-Ischemia Model, John Winter Calvert

Loma Linda University Electronic Theses, Dissertations & Projects

With an incidence approaching 1/4000 live births and as high as 60% in low birth weight infants, cerebral hypoxia-ischemia during the perinatal period is the single most important cause of acute mortality and chronic disability in newborns. Herein, we tested the hypothesis that following a hypoxic-ischemic insult hyperbaric oxygen (HBO) treatment can restore high energy metabolite levels in the affected regions of the brain and through this increase in energy levels ameliorate the spread of cell death following the insult. We also investigated if an additional mechanism by which HBO affords its neuroprotection is by altering the expression of the …

Stability Of The Miniscrew-Bone Interface: Reverse Torque Values In Rabbits, Daniel John Drye

Loma Linda University Electronic Theses, Dissertations & Projects

Introduction: Miniscrews are used in orthodontics as practical temporary anchorage devices (TAD's). The purpose of this animal study was to measure reverse torque values for Absoanchor 1.2 mm and Micerium 1.5mm miniscrews at 0, 2, and 12 weeks under loaded and unloaded conditions.

Methods: Ninety-six miniscrews were placed in the femora of twelve rabbits and allowed to heal for either two or twelve weeks. Half of the fixtures were loaded immediately with NiTi open coil springs producing a force of 150-200g and the other half served as unloaded controls. For each of the healing times, two and twelve weeks, …

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

Experimentation Collection

Animal tests yield misleading results.

Animal Models Of Head Trauma, Ibolja Cernak

Biomedicine and Animal Models in Research Collection

Animal models of traumatic brain injury (TBI) are used to elucidate primary and secondary sequelae underlying human head injury in an effort to identify potential neuroprotective therapies for developing and adult brains. The choice of experimental model depends upon both the research goal and underlying objectives. The intrinsic ability to study injuryinduced changes in behavior, physiology, metabolism, the blood/tissue interface, the blood brain barrier, and/or inflammatory- and immune-mediated responses, makes in vivo TBI models essential for neurotrauma research. Whereas human TBI is a highly complex multifactorial disorder, animal trauma models tend to replicate only single factors involved in the pathobiology …

Histological Comparison Of White And Gray Mta In Repair Of Furcation Perforations, Miguel Elias Mego

Loma Linda University Electronic Theses, Dissertations & Projects

Mineral trioxide aggregate (MTA) has been shown to promote regeneration of the periodontal apparatus when used as a repair material in furcation perforations. Two variations of MTA (Gray and White) have been introduced to the dental market. The purpose of this study was to histologically compare the in vivo response to immediate furcation perforation repair using gray or white MTA in beagle dogs.

Under general anesthesia, non-surgical root canal therapy and furcal perforations were performed on sixteen mandibular premolars of eight 2-year old beagle dogs. The perforations were immediately repaired with either white (n=8) or gray (n=8) MTA. The animals …

Chimpanzees In Research: Past, Present, And Future, Kathleen Conlee, Sarah T. Boysen

State of the Animals 2005

Although the welfare of chimpanzees encompasses many issues, this chapter addresses their use in research, including their historical and current use in the United States, ethical and scientific concerns, public opinion, international legislation, and future directions.

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

Experimentation Collection

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 …

Ld50 Testing Of Botulinum Toxin For Use As A Cosmetic, Martin L. Stephens, Michael Balls

Experimentation Collection

In 2003, the Fund for the Replacement of Animals in Medical Experiments (FRAME) revealed that the potency of botulinum toxin for use as a popular wrinkle treatment is assessed by using the LD50 Test. The endpoint in this mouse-based testing is death through suffocation. In 2004, The Humane Society of the United States (HSUS) sought to work with Allergan, the US-based manufacturer of Botox® Cosmetic, and the U.S. Food and Drug Administration (FDA), on ways to refine, reduce, and replace this LD50 testing. This article summarises The HSUS’s campaign in the United States and provides an update on FRAME’s continuing …

Non-Human Primates In Medical Research And Drug Development: A Critical Review, Jarrod Bailey

Laboratory Experiments Collection

There is much current debate surrounding the use of non-human primates (NHPs) in medical research and drug development. This review, stimulated by calls for evidence from UK-based inquiries into NHP research, takes a critical view in order to provide some important balance against papers supporting NHP research and calling for it to be expanded. We show that there is a paucity of evidence to demonstrate the positive contribution or successful translation of NHP research to human medicine, that there is a great deal of often overlooked data showing NHP research to be irrelevant, unnecessary, even hazardous to human health and …

Arkansas Animal Science Department Report 2004, Zelpha B. Johnson, D. Wayne Kellogg

Arkansas Agricultural Experiment Station Research Series

No abstract provided.