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Selected Works

2016

Animal model

Articles 1 - 11 of 11

Full-Text Articles in Medicine and Health Sciences

The Future Of Teratology Research Is In Vitro, Jarrod Bailey, Andrew Knight, Jonathan Balcombe Sep 2016

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 …

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Monkey-Based Research On Human Disease: The Implications Of Genetic Differences, Jarrod Bailey Sep 2016

Monkey-Based Research On Human Disease: The Implications Of Genetic Differences, Jarrod Bailey

Jarrod Bailey, PhD

Assertions that the use of monkeys to investigate human diseases is valid scientifically are frequently based on a reported 90–93% genetic similarity between the species. Critical analyses of the relevance of monkey studies to human biology, however, indicate that this genetic similarity does not result in sufficient physiological similarity for monkeys to constitute good models for research, and that monkey data do not translate well to progress in clinical practice for humans. Salient examples include the failure of new drugs in clinical trials, the highly different infectivity and pathology of SIV/HIV, and poor extrapolation of research on Alzheimer’s disease, Parkinson’s …

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Lessons From Chimpanzee-Based Research On Human Disease: The Implications Of Genetic Differences, Jarrod Bailey Sep 2016

Lessons From Chimpanzee-Based Research On Human Disease: The Implications Of Genetic Differences, Jarrod Bailey

Jarrod Bailey, PhD

Assertions that the use of chimpanzees to investigate human diseases is valid scientifically are frequently based on a reported 98–99% genetic similarity between the species. Critical analyses of the relevance of chimpanzee studies to human biology, however, indicate that this genetic similarity does not result in sufficient physiological similarity for the chimpanzee to constitute a good model for research, and furthermore, that chimpanzee data do not translate well to progress in clinical practice for humans. Leading examples include the minimal citations of chimpanzee research that is relevant to human medicine, the highly different pathology of HIV/AIDS and hepatitis C virus …

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The Usefulness Of Systematic Reviews Of Animal Experiments For The Design Of Preclinical And Clinical Studies, Rob B.M. De Vries, Kimberley E. Weaver, Marc T. Avey, Martin Stephens, Emily S. Sena, Marlies Leenaars Jul 2016

The Usefulness Of Systematic Reviews Of Animal Experiments For The Design Of Preclinical And Clinical Studies, Rob B.M. De Vries, Kimberley E. Weaver, Marc T. Avey, Martin Stephens, Emily S. Sena, Marlies Leenaars

Martin Stephens, PhD

The question of how animal studies should be designed, conducted, and analyzed remains underexposed in societal debates on animal experimentation. This is not only a scientific but also amoral question. After all, if animal experiments are not appropriately designed, conducted, and analyzed, the results produced are unlikely to be reliable and the animals have in effect been wasted. In this article, we focus on one particular method to address this moral question, namely systematic reviews of previously performed animal experiments. We discuss how the design, conduct, and analysis of future (animal and human) experiments may be optimized through such systematic …

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Feasibility Of Atrial Delivery And Tracking Of Stem Cells In A Porcine Model, Nina Garlie, Timothy Hacker, Eric G. Schmuck, Jill Koch, Jayant Khitha, Amish Raval, Indrajit Choudhuri Jun 2016

Feasibility Of Atrial Delivery And Tracking Of Stem Cells In A Porcine Model, Nina Garlie, Timothy Hacker, Eric G. Schmuck, Jill Koch, Jayant Khitha, Amish Raval, Indrajit Choudhuri

Indrajit Choudhuri, MD

Background: Many patients undergoing open heart surgery have sinus node dysfunction and atrial fibrillation, leading to adverse outcomes. Mesenchymal stem cells (MSC) delivered at the time of surgery may have a reparative effect on atrial tissue, thereby improving sinus node function and reducing or preventing atrial fibrillation. Stem cell delivery to the atrium is entirely unstudied. This is a significant gap in medical research, as atrial disease contributes significantly to health care costs. Purpose: The purpose of this pilot study is to establish a technique to deliver MSC to the atria through an open-chest model, to assess the safety of …

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High Fat Diet-Induced Obesity Increases The Formation Of Colon Polyps Induced By Azoxymethane In Mice, Jiezhong Chen, Xu-Feng Huang Jun 2016

High Fat Diet-Induced Obesity Increases The Formation Of Colon Polyps Induced By Azoxymethane In Mice, Jiezhong Chen, Xu-Feng Huang

Xu-Feng Huang

Background: Obesity has been found to be associated with colon cancer. However, the mechanism of this relationship is unclear and thus a good animal model is required. Our previous research showed that some mice developed diet-induced obesity (DIO) whilst others were diet-resistant (DR) when fed a high-fat diet. Methods: In the present study, we have tested the effects of a high-fat diet on the formation of colon polyps induced by azoxymethane (AOM) in both DIO and DR mice. Results: We found that the DIO mice have developed 2.5 times of polyps compared to the DR mice (P<0.05) and 3.4 …

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Non-Animal Methodologies Within Biomedical Research And Toxicity Testing, Andrew Knight Apr 2016

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 …

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The Future Of Teratology Research Is In Vitro, Jarrod Bailey, Andrew Knight, Jonathan Balcombe Apr 2016

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 …

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Exonic Sine Insertion In Stk38l Causes Canine Early Retinal Degeneration (Erd), Orly Goldstein, Anna V. Kukekova, Gustavo D. Aguirre, Gregory M. Acland Feb 2016

Exonic Sine Insertion In Stk38l Causes Canine Early Retinal Degeneration (Erd), Orly Goldstein, Anna V. Kukekova, Gustavo D. Aguirre, Gregory M. Acland

Gustavo D. Aguirre, VMD, PhD

Fine mapping followed by candidate gene analysis of erd — a canine hereditary retinal degeneration characterized by aberrant photoreceptor development — established that the disease cosegregates with a SINE insertion in exon 4 of the canine STK38L/NDR2 gene. The mutation removes exon 4 from STK38L transcripts and is predicted to remove much of the N terminus from the translated protein, including binding sites for S100B and Mob proteins, part of the protein kinase domain, and a Thr-75 residue critical for autophosphorylation. Although known to have roles in neuronal cell function, the STK38L pathway has not previously been implicated in normal …

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Posterior Segment Approach For Subretinal Transplantation Or Injection In The Canine Model, Maria E. Verdugo, Julie Alling, Eliot Lazar, Manuel Del Cerro, Jharna Ray, Gustavo D. Aguirre Feb 2016

Posterior Segment Approach For Subretinal Transplantation Or Injection In The Canine Model, Maria E. Verdugo, Julie Alling, Eliot Lazar, Manuel Del Cerro, Jharna Ray, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

A posterior segment approach for cell transplantation or injection into the subretinal space of the dog has been developed. Controlled penetration to the subretinal space was achieved using a 29-gauge injection cannula, either blunted or with a 30° sharpened bevel, and partially ensheathed with moveable plastic tubing. Depending on the injection volume used, the retina detached, and the fluid was reabsorbed within 1–3 weeks, although for smaller volumes the retina reattached within a matter of days. The optimal injection volume used was between 100 and 150 μl, or two injections of 55 μl each. By ophthalmoscopy following the surgery, it …

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Application Of A New Subretinal Injection Device In The Dog, András M. Komáromy, Signe E. Varner, Eugene De Juan, Gregory M. Acland, Gustavo D. Aguirre Feb 2016

Application Of A New Subretinal Injection Device In The Dog, András M. Komáromy, Signe E. Varner, Eugene De Juan, Gregory M. Acland, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

The use of a new subretinal injection device (RetinaJect™ Subretinal Cannula, SurModics, Inc., Eden Prairie, MN) to access the subretinal space in the canine model was evaluated. Subretinal injections were performed in 33 mongrel dogs between 2 and 52 months of age (median = 9 months). In 5 normal dogs the injection of 150 μl saline or India ink occurred by using a conventional subretinal injection device (CSID) with a 30-gauge anterior chamber irrigating cannula. The sclera had to be surgically exposed and penetrated before the subretinal injection with the CSID could occur. After removing the CSID, the conjunctiva over …

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