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ILAR Journal

J M Wallace, R L Trundy
Animal research pathology encompasses a wide array of procedures and may involve work with a variety of animal species and hazards. To protect laboratory personnel and ensure data integrity, pathologists must be familiar with the activities performed in their laboratories and the applicable regulatory and safety requirements. Failure to address issues proactively may result in exposure of personnel to hazardous materials and/or collection of data in a manner that does not conform to animal welfare or quality control standards...
February 4, 2019: ILAR Journal
David K Meyerholz, Amanda P Beck
Failure to reproduce results from some scientific studies has raised awareness of the critical need for reproducibility in translational studies. Macroscopic and microscopic examination is a common approach to determine changes in tissues, but text descriptions and visual images have limitations for group comparisons. Semiquantitative scoring is a way of transforming qualitative tissue data into numerical data that allow more robust group comparisons. Semiquantitative scoring has broad uses in preclinical and clinical studies for evaluation of tissue lesions...
January 31, 2019: ILAR Journal
Lon V Kendall, James R Owiny, Erik D Dohm, Katie J Knapek, Erin S Lee, Jennifer H Kopanke, Michael Fink, Sarah A Hansen, Jessica D Ayers
Animal models are critical to the advancement of our knowledge of infectious disease pathogenesis, diagnostics, therapeutics, and prevention strategies. The use of animal models requires thoughtful consideration for their well-being, as infections can significantly impact the general health of an animal and impair their welfare. Application of the 3Rs-replacement, refinement, and reduction-to animal models using biohazardous agents can improve the scientific merit and animal welfare. Replacement of animal models can use in vitro techniques such as cell culture systems, mathematical models, and engineered tissues or invertebrate animal hosts such as amoeba, worms, fruit flies, and cockroaches...
January 22, 2019: ILAR Journal
Daniel Regan, Kelly Garcia, Douglas Thamm
The role of comparative oncology in translational research is receiving increasing attention from drug developers and the greater biomedical research community. Pet dogs with spontaneous cancer are important and underutilized translational models, owing to dogs' large size and relative outbreeding, combined with their high incidence of certain tumor histotypes with significant biological, genetic, and histological similarities to their human tumor counterparts. Dogs with spontaneous tumors naturally develop therapy resistance and spontaneous metastasis, all in the context of an intact immune system...
January 22, 2019: ILAR Journal
Jeffrey I Everitt, Piper M Treuting, Cheryl Scudamore, Rani Sellers, Patricia V Turner, Jerrold M Ward, Caroline J Zeiss
In translational research, animal models are an important tool to aid in decision-making when taking potential therapies into human clinical trials. Recently, there have been a number of papers that have suggested limited concordance of preclinical animal experiments with subsequent human clinical experience. Assessments of preclinical animal studies have led to concerns about the reproducibility of data and have highlighted the need for an emphasis on rigor and quality in the planning, conduct, analysis, and reporting of such studies...
January 9, 2019: ILAR Journal
James R Swearengen
The 8th edition of the Guide for the Care and Use of Laboratory Animals (Guide) is clear in its requirement for each institution to establish and maintain an occupational health and safety (OHS) program as an essential part of the overall program of animal care and use. For over 30 years, AAALAC International has utilized a variety of methods to evaluate this component of OHS programs as part of the accreditation process. AAALAC International began collecting data on site visit findings over 20 years ago using the Guide as a template for establishing the categories and subcategories to which findings are assigned...
January 9, 2019: ILAR Journal
Signe Tandrup Schmidt, Gabriel Kristian Pedersen, Dennis Christensen
Many different adjuvants are currently being developed for subunit vaccines against a number of pathogens and diseases. Rational design is increasingly used to develop novel vaccine adjuvants, which requires extensive knowledge of, for example, the desired immune responses, target antigen-presenting cell subsets, their localization, and expression of relevant pattern-recognition receptors. The adjuvant mechanism of action and efficacy are usually evaluated in animal models, where mice are by far the most used...
January 9, 2019: ILAR Journal
Kathryn Bayne, Patricia V Turner
Globalization of the biomedical research enterprise is occurring at an accelerating pace. Increasingly, scientific collaborations and contracts cross national borders. Assurance that the caliber of animal research and animal welfare are consistent among countries and that such animal use is done in a humane and conscientious manner is of significant concern to the scientific community, the general public, and other stakeholders. Bridging these international collaborations is a clear scientific imperative for statistical validity of the data and reproducibility of results to ensure the animal use is both meaningful and impactful...
January 8, 2019: ILAR Journal
Yohannes G Asfaw, Randall Reynolds, Scott Alderman, John N Norton
The procedures necessary to perform testing in a veterinary diagnostic laboratory have inherent associated risks to personnel in regard to exposure to infectious agents. In research institutions animals can be experimentally infected, acquire naturally occurring infections and can also be exposed to other hazards such as toxic chemicals or radiologic entities. A critical component of the use of animals in a research environment is the collaboration between the responsible researcher and the veterinary diagnostic laboratory with the institutional health and safety professionals to ensure that the proper engineering controls, personal protective equipment, laboratory procedures and training are in place for personnel working with the animals or their specimens...
December 22, 2018: ILAR Journal
Brad Bolon, Wallace Baze, Christopher J Shilling, Kendy L Keatley, Daniel J Patrick, Kenneth A Schafer
Development of new biomedical products necessitates nonclinical safety assessment in animals as a means of assessing potential risk to human patients. Pivotal nonclinical safety studies that support human clinical trials are performed according to Good Laboratory Practice (GLP) guidelines, which are designed to ensure that the study was conducted under carefully controlled conditions using standardized and validated procedures that will yield a reliable, reproducible, and traceable data set. The GLP guidelines established by different regulatory agencies address organizational structure, personnel responsibilities, personnel training practices, quality assurance (ensuring compliance), facilities, equipment, standard operating procedures, study documentation (record keeping), and record and sample retention...
December 19, 2018: ILAR Journal
Jeffrey L Platt, Marilia Cascalho, Jorge A Piedrahita
For more than a century, transplantation of tissues and organs from animals into man, xenotransplantation, has been viewed as a potential way to treat disease. Ironically, interest in xenotransplantation was fueled especially by successful application of allotransplantation, that is, transplantation of human tissue and organs, as a treatment for a variety of diseases, especially organ failure because scarcity of human tissues limited allotransplantation to a fraction of those who could benefit. In principle, use of animals such as pigs as a source of transplants would allow transplantation to exert a vastly greater impact than allotransplantation on medicine and public health...
December 12, 2018: ILAR Journal
Lesley A Colby, Lois Zitzow
Zoonoses, diseases transmitted between animals and humans, have been a concern in laboratory animal medicine for decades. Exposure to zoonotic organisms not only poses health risks to personnel and research animals but may also affect research integrity. Early laboratory animal programs were ineffective at excluding and preventing transmission of zoonotic diseases: the health status of the animals were often unknown, endemic diseases occurred frequently, housing conditions were less controlled, and veterinary care programs were decentralized...
December 12, 2018: ILAR Journal
Kathleen Gabrielson, Robert Maronpot, Sébastien Monette, Coraline Mlynarczyk, Yuval Ramot, Abraham Nyska, Polina Sysa-Shah
Preclinical noninvasive imaging can be an indispensable tool for studying animal models of disease. In vivo imaging to assess anatomical, functional, and molecular features requires verification by a comparison to the macroscopic and microscopic morphological features, since all noninvasive in vivo imaging methods have much lower resolution than standard histopathology. Comprehensive pathological evaluation of the animal model is underutilized; yet, many institutions have veterinary or human pathologists with necessary comparative pathology expertise...
December 12, 2018: ILAR Journal
Jason S Villano, Susan E Vleck, Stephen A Felt, Daniel D Myers, Patrick A Lester
Research using laboratory animals has been revolutionized by the creation of humanized animal models, which are immunodeficient animals engrafted with human cells, tissues, or organs. These animal models provide the research community a unique and promising opportunity to mimic a wide variety of disease conditions in humans, from infectious disease to cancer. A vast majority of these models are humanized mice like those injected with human CD34+ hematopoietic stem cells and patient-derived xenografts. With this technology comes the need for the animal research enterprise to understand the inherent and potential risks, such as exposure to bloodborne pathogens, associated with the model development and research applications...
December 12, 2018: ILAR Journal
Famke Aeffner, Hibret A Adissu, Michael C Boyle, Robert D Cardiff, Erik Hagendorn, Mark J Hoenerhoff, Robert Klopfleisch, Susan Newbigging, Dirk Schaudien, Oliver Turner, Kristin Wilson
Advancements in technology and digitization have ushered in novel ways of enhancing tissue-based research via digital microscopy and image analysis. Whole slide imaging scanners enable digitization of histology slides to be stored in virtual slide repositories and to be viewed via computers instead of microscopes. Easier and faster sharing of histologic images for teaching and consultation, improved storage and preservation of quality of stained slides, and annotation of features of interest in the digital slides are just a few of the advantages of this technology...
December 7, 2018: ILAR Journal
Nana H Overgaard, Timothy M Fan, Kyle M Schachtschneider, Daniel R Principe, Lawrence B Schook, Gregers Jungersen
The immune system plays dual roles in response to cancer. The host immune system protects against tumor formation via immunosurveillance; however, recognition of the tumor by immune cells also induces sculpting mechanisms leading to a Darwinian selection of tumor cell variants with reduced immunogenicity. Cancer immunoediting is the concept used to describe the complex interplay between tumor cells and the immune system. This concept, commonly referred to as the three E's, is encompassed by 3 distinct phases of elimination, equilibrium, and escape...
November 22, 2018: ILAR Journal
Susan A Elmore, Robert Cardiff, Mark F Cesta, Georgios V Gkoutos, Robert Hoehndorf, Charlotte M Keenan, Colin McKerlie, Paul N Schofield, John P Sundberg, Jerrold M Ward
The need for international collaboration in rodent pathology has evolved since the 1970s and was initially driven by the new field of toxicologic pathology. First initiated by the World Health Organization's International Agency for Research on Cancer for rodents, it has evolved to include pathology of the major species (rats, mice, guinea pigs, nonhuman primates, pigs, dogs, fish, rabbits) used in medical research, safety assessment, and mouse pathology. The collaborative effort today is driven by the needs of the regulatory agencies in multiple countries, and by needs of research involving genetically engineered animals, for "basic" research and for more translational preclinical models of human disease...
November 22, 2018: ILAR Journal
Gaylen L Edwards, Michael J Azain, Andrew Parks
The use of agricultural animals in biomedical research is increasing. Their overall size and metabolic rate, organ size, longer gestation period, and other physiological similarities make them good candidates for animal models of human disease. There are a number of special considerations for use of traditional farm animals for biomedical research. Differences in physical plant infrastructure, handling equipment, training of personnel, and potential zoonoses are some of the important considerations when traditional farm animals are used in biomedical research...
November 22, 2018: ILAR Journal
Sofie M R Starbæk, Louise Brogaard, Harry D Dawson, Allen D Smith, Peter M H Heegaard, Lars E Larsen, Gregers Jungersen, Kerstin Skovgaard
Influenza is a viral respiratory disease having a major impact on public health. Influenza A virus (IAV) usually causes mild transitory disease in humans. However, in specific groups of individuals such as severely obese, the elderly, and individuals with underlying inflammatory conditions, IAV can cause severe illness or death. In this review, relevant small and large animal models for human IAV infection, including the pig, ferret, and mouse, are discussed. The focus is on the pig as a large animal model for human IAV infection as well as on the associated innate immune response...
November 22, 2018: ILAR Journal
Dorcas P O'Rourke, Cecile L Baccanale, Michael K Stoskopf
Aquatic vertebrates and cephalopods, amphibians, reptiles, and birds offer unique safety and occupational health challenges for laboratory animal personnel. This paper discusses environmental, handling, and zoonotic concerns associated with these species.
November 21, 2018: ILAR Journal
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