Life Sciences Commons^™

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

Andrew Knight, PhD

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 …

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

Andrew Knight, Ph.D.

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 …

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 …

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

Jonathan Balcombe, PhD

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 …

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

Jonathan Balcombe, PhD

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 …

What It Is To Be A Dog: A Qualitative Method For The Study Of Animals Other Than Humans, Kenneth J. Shapiro

Kenneth J. Shapiro, PhD

No abstract provided.

A New Invasiveness Scale: Its Role In Reducing Animal Distress, Kenneth J. Shapiro, Peter B. Field

Kenneth J. Shapiro, PhD

No abstract provided.

Animal Model Research: The Apples And Oranges Quandary, Kenneth J. Shapiro

Kenneth J. Shapiro, PhD

In this paper, I explore the premises underlying the problem of the evaluation of animal models. I argue that the presence of similarities and differences between the model and the modelled, although historically and currently a dominant antinomy framing evaluation, is not a bottom-line consideration. What is critical is 1) whether we learn and 2) whether we improve treatment through the animal model research. Similarity between model and modelled and the closely related concept of validity are not coterminus with these critical evaluative measures. In fact, differences between the model and modelled also can provide impetus to new understanding and …

Clinical Methods To Quantify Trunk Mobility In An Elite Male Surfing Population, James Furness, Michael Climstein, Jeremy Sheppard, Allan Abbott, Wayne Hing

Allan D. Abbott

Background

Thoracic mobility in the sagittal and horizontal planes are key requirements in the sport of surfing; however to date the normal values of these movements have not yet been quantified in a surfing population.

Objectives

To develop a reliable method to quantify thoracic mobility in the sagittal plane; to assess the reliability of an existing thoracic rotation method, and quantify thoracic mobility in an elite male surfing population.

Design

Clinical Measurement, reliability and comparative study.

Methods

A total of 30 subjects were used to determine the reliability component. 15 elite surfers were used as part of a comparative analysis …

Clinical Methods To Quantify Trunk Mobility In An Elite Male Surfing Population, James Furness, Michael Climstein, Jeremy Sheppard, Allan Abbott, Wayne Hing

Wayne Hing

Background Thoracic mobility in the sagittal and horizontal planes are key requirements in the sport of surfing; however to date the normal values of these movements have not yet been quantified in a surfing population. Objectives To develop a reliable method to quantify thoracic mobility in the sagittal plane; to assess the reliability of an existing thoracic rotation method, and quantify thoracic mobility in an elite male surfing population. Design Clinical Measurement, reliability and comparative study. Methods A total of 30 subjects were used to determine the reliability component. 15 elite surfers were used as part of a comparative analysis …

Antiretroviral Drugs-Loaded Nanoparticles Fabricated By Dispersion Polymerization With Potential For Hiv/Aids Treatment, Winston A. Anderson

Winston Anderson

Elucidation Of The Anatomy Of A Satiety Network: Focus On Connectivity Of The Parabrachial Nucleus In The Adult Rat, Györgyi Zséli, Barbara Vida, Anais Martinez, Ronald M. Lechan, Arshad M. Khan, Csaba Fekete

Arshad M. Khan, Ph.D.

Β-Thujaplicin: A Soil Antifungal, Dennis J. Baumgardner

Dennis J. Baumgardner, MD

Background: β-thujaplicin (β-Th), also known as hinokitiol, naturally occurs in cedar mulch, is found in personal care products and has in vitro antitumor activities. It is antibacterial and antifungal, but has not been tested on soil. Scedosporium apiospermum (Sce) is an emerging “extremophile” fungal pathogen found in built outdoor environments. Purpose: Pilot β-Th as “natural” soil antimicrobial or for isolation of extremophiles, and to explore β-Th resistance as selective advantage to Sce in mulched landscape. Methods: A variety of outdoor and indoor environments were used for 2 sets of 24 paired soil samples. Soil/H20 slurry (0.1 ml) was spread on …

Clinical Light Exposure, Photoreceptor Degeneration, And Ap-1 Activation: A Cell Death Or Cell Survival Signal In The Rhodopsin Mutant Retina?, Danian Gu, William Beltran, Zexiao Li, Gregory M. Acland, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

PURPOSE. The T4R RHO mutant dog retina shows retinal degeneration with exposures to light comparable to those used in clinical eye examinations of patients. To define the molecular mechanisms of the degeneration, AP-1 DNA-binding activity, composition, posttranslational modification of the protein complex, and modulation of ERK/MAPK signaling pathways were examined in light-exposed mutant retinas. METHODS. Dark-adapted retinas were exposed to short-duration light flashes from a retinal camera used clinically for retinal photography and were collected at different time points after exposure. Electrophoretic mobility shift assay (EMSA), supershift EMSA, Western blot analysis, and immunocytochemistry were used to examine AP-1 signaling. RESULTS. …

Bestrophin Gene Mutations Cause Canine Multifocal Retinopathy: A Novel Animal Model For Best Disease, Karina E. Guziewicz, Barbara Zangerl, Sarah J. Lindauer, Robert F. Mullins, Lynne S. Sandmeyer, Bruce H. Grahn, Edwin M. Stone, Gregory M. Acland, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

PURPOSE. Canine multifocal retinopathy (cmr) is an autosomal recessive disorder of multiple dog breeds. The disease shares a number of clinical and pathologic similarities with Best macular dystrophy (BMD), and cmr is proposed as a new large animal model for Best disease. METHODS. cmr was characterized by ophthalmoscopy and histopathology and compared with BMD-affected patients. BEST1 (alias VMD2), the bestrophin gene causally associated with BMD, was evaluated in the dog. Canine ortholog cDNA sequence was cloned and verified using RPE/choroid 5′- and 3′-RACE. Expression of the canine gene transcripts and protein was analyzed by Northern and Western blotting and immunocytochemistry. …

Recombinant Aav-Mediated Best1 Transfer To The Retinal Pigment Epithelium: Analysis Of Serotype-Dependent Retinal Effects, Karina E. Guziewicz, Barbara Zangerl, András M. Komáromy, Simone Iwabe, Vincent A. Chiodo, Sanford L. Boye, William W. Hauswirth, William Beltran, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

Mutations in the BEST1 gene constitute an underlying cause of juvenile macular dystrophies, a group of retinal disorders commonly referred to as bestrophinopathies and usually diagnosed in early childhood or adolescence. The disease primarily affects macular and paramacular regions of the eye leading to major declines in central vision later in life. Currently, there is no cure or surgical management for BEST1-associated disorders. The recently characterized human disease counterpart, canine multifocal retinopathy (cmr), recapitulates a full spectrum of clinical and molecular features observed in human bestrophinopathies and offers a valuable model system for development and testing of therapeutic strategies. In …

The Shellfish Corner -- Water Quality And Culture Of Shellfish In Prohibited Waters, Michael A. Rice

Michael A Rice

Interleukin 10 Restores Gastric Emptying, Electrical Activity, And Interstitial Cells Of Cajal Networks In Diabetic Mice, Anthony J. Bauer

Anthony Bauer

Antagonism Of Triazolam Self-Administration In Rhesus Monkeys Responding Under A Progressive-Ratio Schedule: In Vivo Apparent Pa2 Analysis, Bradford D. Fischer Phd, Donna M. Platt, Sundari K. Rallapalli, Ojas A. Namjoshi, James M. Cook, James K. Rowlett

Bradford Fischer

No abstract provided.

Inga Khachaturova V. Shaun Rourke - Dismissal Of Injunction.Pdf

Khachaturova V. Rourke - Dismissal of Injunction

The Relationship Of Body Composition To Countermovement Vertical Jump Characteristics Across Loaded Conditions, C. J. Macdonald, H. S. Lamont, J. C. Smith, J. C. Cholewa, A. M. Suppe, Jeremy A. Gentles, L. D. Hurlbert

Jeremy A. Gentles

No abstract provided.