Adjuvants in Laboratory Animals: evaluation of immunostimulating properties and side effects of Freund's complete adjuvant and alternative adjuvants in immunization procedures

The body has a variety of defense mechanisms to protect it against invasion of potentially harmful agents such as viruses, bacteria, and parasites. The first line of defense Is a more physical barrier e.g. skin and mucosa. When organisms succeed in passing this first line of defense and enter the body, the immune system is activated and the ensuing immune response generally leads to elimination of the invaders and often results in resistance to the organism. The immune response involves the specific recognition of the organism which leads to humoral and/or cellular immunity and memory. Through the formation of memory cells the immune system is capable of responding to the same organism more rapid and effective upon subsequent encounter. In the humoral immune response, antibody producing B cells playa central role. Antibodies are secreted in body fluids and can bind to organisms with high specificity. Cellular immunity is primarily exerted by T cells, consisting of cytotoxic T cells, which kill virus-infected and tumor cells, or helper T cells which regulate the function of other cells via secreted cytokines. For different reasons, immune responses can be evoked in humans or animals via injection of an antigen (= substance to which an immune response is induced)

A search filter for increasing the retrieval of animal studies in Embase

Collecting and analysing all available literature before starting a new animal experiment is important and it is indispensable when writing systematic reviews of animal research. In practice, finding all animal studies relevant to a specific research question turns out to be anything but simple. In order to facilitate this search process, we previously developed a search filter for retrieving animal studies in the most often used biomedical database, PubMed. It is a general requirement for systematic reviews, however, that at least two databases are searched. In this report, we therefore present a similar search filter for a second important database, namely Embase. We show that our filter retrieves more animal studies than (a combination of) the options currently available in Embase. Our search filters for PubMed and Embase therefore represent valuable tools for improving the quality of (systematic) reviews and thereby of new animal experiments

Enhancing search efficiency by means of a search filter for finding all studies on animal experimentation in PubMed

Collecting and analysing all available literature before starting an animal experiment is important and it is indispensable when writing a systematic review (SR) of animal research. Writing such review prevents unnecessary duplication of animal studies and thus unnecessary animal use (Reduction). One of the factors currently impeding the production of ‘high-quality’ SRs in laboratory animal science is the fact that searching for all available literature concerning animal experimentation is rather difficult. In order to diminish these difficulties, we developed a search filter for PubMed to detect all publications concerning animal studies. This filter was compared with the method most frequently used, the PubMed Limit: Animals, and validated further by performing two PubMed topic searches. Our filter performs much better than the PubMed limit: it retrieves, on average, 7% more records. Other important advantages of our filter are that it also finds the most recent records and that it is easy to use. All in all, by using our search filter in PubMed, all available literature concerning animal studies on a specific topic can easily be found and assessed, which will help in increasing the scientific quality and thereby the ethical validity of animal experiments

A step-by-step guide to systematically identify all relevant animal studies

Before starting a new animal experiment, thorough analysis of previously performed experiments is essential from a scientific as well as from an ethical point of view. The method that is most suitable to carry out such a thorough analysis of the literature is a systematic review (SR). An essential first step in an SR is to search and find all potentially relevant studies. It is important to include all available evidence in an SR to minimize bias and reduce hampered interpretation of experimental outcomes. Despite the recent development of search filters to find animal studies in PubMed and EMBASE, searching for all available animal studies remains a challenge. Available guidelines from the clinical field cannot be copied directly to the situation within animal research, and although there are plenty of books and courses on searching the literature, there is no compact guide available to search and find relevant animal studies. Therefore, in order to facilitate a structured, thorough and transparent search for animal studies (in both preclinical and fundamental science), an easy-to-use, step-by-step guide was prepared and optimized using feedback from scientists in the field of animal experimentation. The step-by-step guide will assist scientists in performing a comprehensive literature search and, consequently, improve the scientific quality of the resulting review and prevent unnecessary animal use in the future

Publication Bias in Laboratory Animal Research: A Survey on Magnitude, Drivers, Consequences and Potential Solutions

Contains fulltext : 109229.pdf (publisher's version ) (Open Access)CONTEXT: Publication bias jeopardizes evidence-based medicine, mainly through biased literature syntheses. Publication bias may also affect laboratory animal research, but evidence is scarce. OBJECTIVES: To assess the opinion of laboratory animal researchers on the magnitude, drivers, consequences and potential solutions for publication bias. And to explore the impact of size of the animals used, seniority of the respondent, working in a for-profit organization and type of research (fundamental, pre-clinical, or both) on those opinions. DESIGN: Internet-based survey. SETTING: All animal laboratories in The Netherlands. PARTICIPANTS: Laboratory animal researchers. MAIN OUTCOME MEASURE(S): Median (interquartile ranges) strengths of beliefs on 5 and 10-point scales (1: totally unimportant to 5 or 10: extremely important). RESULTS: Overall, 454 researchers participated. They considered publication bias a problem in animal research (7 (5 to 8)) and thought that about 50% (32-70) of animal experiments are published. Employees (n = 21) of for-profit organizations estimated that 10% (5 to 50) are published. Lack of statistical significance (4 (4 to 5)), technical problems (4 (3 to 4)), supervisors (4 (3 to 5)) and peer reviewers (4 (3 to 5)) were considered important reasons for non-publication (all on 5-point scales). Respondents thought that mandatory publication of study protocols and results, or the reasons why no results were obtained, may increase scientific progress but expected increased bureaucracy. These opinions did not depend on size of the animal used, seniority of the respondent or type of research. CONCLUSIONS: Non-publication of "negative" results appears to be prevalent in laboratory animal research. If statistical significance is indeed a main driver of publication, the collective literature on animal experimentation will be biased. This will impede the performance of valid literature syntheses. Effective, yet efficient systems should be explored to counteract selective reporting of laboratory animal research

The Usefulness of Systematic Reviews of Animal Experiments for the Design of Preclinical and Clinical Studies

Abstract 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 a moral 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 reviews. In particular, we illustrate how these reviews can help improve the methodological quality of animal experiments, make the choice of an animal model and the translation of animal data to the clinic more evidence-based, and implement the 3Rs. Moreover, we discuss which measures are being taken and which need to be taken in the future to ensure that systematic reviews will actually contribute to optimizing experimental design and thereby to meeting a necessary condition for making the use of animals in these experiments justified