Animal Experiments and their Alternatives in Psychiatry

1988 ◽  
Vol 15 (4) ◽  
pp. 313-318
Author(s):  
Anthony Stevens
Keyword(s):  
Animal Models ◽  
Human Study ◽  
Animal Experiments ◽  
Experimental Production ◽  
Potential Utility ◽  
Pharmacological Agents ◽  
Wide Range ◽  
Influential Paper ◽  
Adequate Data ◽  
Human Primate

During the last twenty years, the most enthusiastic advocates of the use of animal models in the study of human psychiatric dysfunction have been Harlow and Suomi. In an influential paper, Induced Depression in Monkeys (1974), they argued that more extensive use of non-human primates “would have great potential utility since many manipulations and measurements presently prohibited in human study by ethical and practical considerations could be readily performed on non-human primate subjects in well-controlled experimental environments.” Harlow & Suomi concluded this paper with the following statement: “The results obtained to date on induced depression in monkeys show that proper and profound depressions can be produced relatively easily by a variety of techniques. These induced depressions either bear a close resemblance to human depression or have such similarity as to suggest that closely correlated human and animal depressive patterns may be achieved with refined techniques. The results to date also provide adequate data for the conduct of meaningful researches on the effects of pharmacological agents which either enhance, inhibit or preclude the experimental production of depression. Further, the existence of firm and fast monkey depression syndromes offers vast opportunities for testing a wide range of therapeutic techniques, either behavioural or biochemical.”

scholarly journals Dynamics of salivary markers of kidney functions in acute and chronic kidney diseases

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Alexandra Gaál Kovalčíková ◽  
Kristína Pavlov ◽  
Róbert Lipták ◽  
Marianna Hladová ◽  
Emese Renczés ◽  
...  
Keyword(s):  
Renal Failure ◽  
Animal Models ◽  
Ischemia Reperfusion Injury ◽  
Kidney Diseases ◽  
Ischemia Reperfusion ◽  
Human Study ◽  
Animal Experiments ◽  
Kidney Injury ◽  
Plasma Urea ◽  
Non Invasive

AbstractSaliva can be used as an alternative diagnostic fluid enabling easy and non-invasive disease monitoring. Urea and creatinine can be measured in saliva and both were shown to be increased in renal failure. However, the dynamics of these markers during the development of kidney diseases is unknown. We aimed to describe the dynamics of salivary urea and creatinine in various animal models of acute kidney injury (AKI) and chronic kidney disease (CKD) and in patients with different stages AKI or CKD. Ninety Wistar rats underwent bilateral nephrectomy (BNX), ischemia–reperfusion injury (IRI) or glycerol-induced kidney injury to model AKI. CKD was modelled using 5/6 nephrectomy. In the clinical part 57 children aged 12.6 ± 4.9 years with AKI (n = 11) or CKD (n = 46) and 29 healthy controls (aged 10.2 ± 3.7 years) were enrolled. Saliva and blood samples were collected in both, animal experiments and the human study. In animal models of AKI, plasma urea and creatinine were higher than in controls. An increase of salivary urea and creatinine (twofold) was observed in BNX and IRI, but only after 12 h and 24 h, respectively. In glycerol nephropathy and 5/6 nephrectomy, salivary urea increased (by 100% and by 50%), while salivary creatinine did not change during the observation period. Salivary urea and creatinine were significantly higher in all patients compared to controls (threefold) and in both, AKI and CKD they were associated with the severity of renal failure. Plasma and salivary concentrations correlated only in children with renal failure (R = 0.72 for urea; R = 0.93 for creatinine), but not in controls (R = -0.007 for urea; R = 0.02 for creatinine). Our study indicates that during the development of renal impairment saliva could be used for non-invasive monitoring in higher stages of AKI or CKD, rather than for screening of early stages of kidney diseases.

scholarly journals Mesenchymal stromal cells: what have we learned so far about their therapeutic potential and mechanisms of action?

2021 ◽  
Author(s):  
Francesco Amadeo ◽  
Katherine Trivino Cepeda ◽  
James Littlewood ◽  
Bettina Wilm ◽  
Arthur Taylor ◽  
...  
Keyword(s):  
Animal Models ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Animal Studies ◽  
Therapeutic Potential ◽  
Animal Experiments ◽  
Mechanisms Of Action ◽  
Clinical Translation ◽  
Beneficial Effects ◽  
Wide Range

Mesenchymal stromal cells (MSCs) have been found to be safe and effective in a wide range of animal models of human disease. MSCs have been tested in thousands of clinical trials, but results show that while these cells appear to be safe, they tend to lack efficacy. This has raised questions about whether animal models are useful for predicting efficacy in patients. However, a problem with animal studies is that there is a lack of standardisation in the models and MSC therapy regimes used; there appears to be publication bias towards studies reporting positive outcomes; and the reproducibility of results from animal experiments tends not to be confirmed prior to clinical translation. A further problem is that while some progress has been made towards investigating the mechanisms of action (MoA) of MSCs, we still fail to understand how they work. To make progress, it is important to ensure that prior to clinical translation, the beneficial effects of MSCs in animal studies are real and can be repeated by independent research groups. We also need to understand the MoA of MSCs to assess whether their effects are likely to be beneficial across different species. In this review, we give an overview of the current clinical picture of MSC therapies and discuss what we have learned from animal studies. We also give a comprehensive update of what we know about the MoA of MSCs, particularly in relation to their role in immunomodulation.

scholarly journals COVID-19 Research: Lessons from Non-Human Primate Models

Vaccines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 886
Author(s):  
Laure Albrecht ◽  
Elodie Bishop ◽  
Basile Jay ◽  
Blaise Lafoux ◽  
Marie Minoves ◽  
...  
Keyword(s):  
Public Health ◽  
Animal Models ◽  
Severe Acute Respiratory Syndrome ◽  
Nonhuman Primates ◽  
Clinical Symptoms ◽  
Severe Pneumonia ◽  
Critical Importance ◽  
Vaccine Candidates ◽  
Wide Range ◽  
Human Primate

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19). It emerged from China in December 2019 and rapidly spread across the globe, causing a pandemic with unprecedented impacts on public health and economy. Therefore, there is an urgent need for the development of curative treatments and vaccines. In humans, COVID-19 pathogenesis shows a wide range of symptoms, from asymptomatic to severe pneumonia. Identifying animal models of SARS-CoV-2 infection that reflect the clinical symptoms of COVID-19 is of critical importance. Nonhuman primates (NHPss) correspond to relevant models to assess vaccine and antiviral effectiveness. This review discusses the use of NHPs as models for COVID-19 research, with focus on the pathogenesis of SARS-CoV-2 infection, drug discovery and pre-clinical evaluation of vaccine candidates.

scholarly journals Preclinical Testing of Radiopharmaceuticals for the Detection and Characterization of Osteomyelitis: Experiences from a Porcine Model

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4221
Author(s):  
Aage Kristian Olsen Alstrup ◽  
Svend Borup Jensen ◽  
Ole Lerberg Nielsen ◽  
Lars Jødal ◽  
Pia Afzelius
Keyword(s):  
Animal Model ◽  
Animal Models ◽  
Porcine Model ◽  
Animal Experiments ◽  
Radioactive Tracers ◽  
The Individual ◽  
Selection Of

The development of new and better radioactive tracers capable of detecting and characterizing osteomyelitis is an ongoing process, mainly because available tracers lack selectivity towards osteomyelitis. An integrated part of developing new tracers is the performance of in vivo tests using appropriate animal models. The available animal models for osteomyelitis are also far from ideal. Therefore, developing improved animal osteomyelitis models is as important as developing new radioactive tracers. We recently published a review on radioactive tracers. In this review, we only present and discuss osteomyelitis models. Three ethical aspects (3R) are essential when exposing experimental animals to infections. Thus, we should perform experiments in vitro rather than in vivo (Replacement), use as few animals as possible (Reduction), and impose as little pain on the animal as possible (Refinement). The gain for humans should by far exceed the disadvantages for the individual experimental animal. To this end, the translational value of animal experiments is crucial. We therefore need a robust and well-characterized animal model to evaluate new osteomyelitis tracers to be sure that unpredicted variation in the animal model does not lead to a misinterpretation of the tracer behavior. In this review, we focus on how the development of radioactive tracers relies heavily on the selection of a reliable animal model, and we base the discussions on our own experience with a porcine model.

scholarly journals Animal Models in the Evaluation of the Effectiveness of Phage Therapy for Infections Caused by Gram-Negative Bacteria from the ESKAPE Group and the Reliability of Its Use in Humans

2021 ◽  
Vol 9 (2) ◽  
pp. 206
Author(s):  
Martyna Cieślik ◽  
Natalia Bagińska ◽  
Andrzej Górski ◽  
Ewa Jończyk-Matysiak
Keyword(s):  
Animal Models ◽  
Phage Therapy ◽  
Animal Experiments ◽  
Species Group ◽  
Effectiveness Evaluation ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Enterobacter Species ◽  
The Individual

The authors emphasize how extremely important it is to highlight the role played by animal models in an attempt to determine possible phage interactions with the organism into which it was introduced as well as to determine the safety and effectiveness of phage therapy in vivo taking into account the individual conditions of a given organism and its physiology. Animal models in which phages are used make it possible, among other things, to evaluate the effective therapeutic dose and to choose the possible route of phage administration depending on the type of infection developed. These results cannot be applied in detail to the human body, but the knowledge gained from animal experiments is invaluable and very helpful. We would like to highlight how useful animal models may be for the possible effectiveness evaluation of phage therapy in the case of infections caused by gram-negative bacteria from the ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter species) group of pathogens. In this review, we focus specifically on the data from the last few years.

scholarly journals Methods Used and Application of the Mouse Grimace Scale in Biomedical Research 10 Years On: A Scoping Review

Animals ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 673
Author(s):  
Alexandra L. Whittaker ◽  
Yifan Liu ◽  
Timothy H. Barker
Keyword(s):  
Animal Models ◽  
Mouse Models ◽  
Biomedical Research ◽  
Scoping Review ◽  
Facial Features ◽  
Inclusion Criteria ◽  
Academic Literature ◽  
Research Fields ◽  
Neuroscience Research ◽  
Wide Range

The Mouse Grimace Scale (MGS) was developed 10 years ago as a method for assessing pain through the characterisation of changes in five facial features or action units. The strength of the technique is that it is proposed to be a measure of spontaneous or non-evoked pain. The time is opportune to map all of the research into the MGS, with a particular focus on the methods used and the technique’s utility across a range of mouse models. A comprehensive scoping review of the academic literature was performed. A total of 48 articles met our inclusion criteria and were included in this review. The MGS has been employed mainly in the evaluation of acute pain, particularly in the pain and neuroscience research fields. There has, however, been use of the technique in a wide range of fields, and based on limited study it does appear to have utility for pain assessment across a spectrum of animal models. Use of the method allows the detection of pain of a longer duration, up to a month post initial insult. There has been less use of the technique using real-time methods and this is an area in need of further research.

scholarly journals Bone Morphogenetic Proteins, Carriers, and Animal Models in the Development of Novel Bone Regenerative Therapies

Materials ◽  
2021 ◽  
Vol 14 (13) ◽  
pp. 3513
Author(s):  
Nikola Stokovic ◽  
Natalia Ivanjko ◽  
Drazen Maticic ◽  
Frank P. Luyten ◽  
Slobodan Vukicevic
Keyword(s):  
Animal Models ◽  
Bone Formation ◽  
Bone Morphogenetic Proteins ◽  
Animal Experiments ◽  
Inorganic Materials ◽  
New Bone Formation ◽  
Segmental Bone ◽  
Posterolateral Spinal Fusion ◽  
Regenerative Therapies ◽  
Observation Period

Bone morphogenetic proteins (BMPs) possess a unique ability to induce new bone formation. Numerous preclinical studies have been conducted to develop novel, BMP-based osteoinductive devices for the management of segmental bone defects and posterolateral spinal fusion (PLF). In these studies, BMPs were combined with a broad range of carriers (natural and synthetic polymers, inorganic materials, and their combinations) and tested in various models in mice, rats, rabbits, dogs, sheep, and non-human primates. In this review, we summarized bone regeneration strategies and animal models used for the initial, intermediate, and advanced evaluation of promising therapeutical solutions for new bone formation and repair. Moreover, in this review, we discuss basic aspects to be considered when planning animal experiments, including anatomical characteristics of the species used, appropriate BMP dosing, duration of the observation period, and sample size.

scholarly journals Pathogen Dose in Animal Models of Hemorrhagic Fever Virus Infections and the Potential Impact on Studies of the Immune Response

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 275
Author(s):  
Bryce M. Warner
Keyword(s):  
Immune Response ◽  
Animal Models ◽  
Hemorrhagic Fever ◽  
Virus Infections ◽  
Critical Determinant ◽  
Animal Models Of Disease ◽  
Hemorrhagic Fever Virus ◽  
Immune Correlates ◽  
Clinical Drug Development ◽  
Wide Range

Viral hemorrhagic fever viruses come from a wide range of virus families and are a significant cause of morbidity and mortality worldwide each year. Animal models of infection with a number of these viruses have contributed to our knowledge of their pathogenesis and have been crucial for the development of therapeutics and vaccines that have been approved for human use. Most of these models use artificially high doses of virus, ensuring lethality in pre-clinical drug development studies. However, this can have a significant effect on the immune response generated. Here I discuss how the dose of antigen or pathogen is a critical determinant of immune responses and suggest that the current study of viruses in animal models should take this into account when developing and studying animal models of disease. This can have implications for determination of immune correlates of protection against disease as well as informing relevant vaccination and therapeutic strategies.

scholarly journals Elucidating the Beneficial Role of PPAR Agonists in Cardiac Diseases

2018 ◽  
Vol 19 (11) ◽  
pp. 3464 ◽  
Author(s):  
Zaza Khuchua ◽  
Aleksandr I. Glukhov ◽  
Arnold W. Strauss ◽  
Sabzali Javadov
Keyword(s):  
Animal Models ◽  
Hormone Receptors ◽  
Lipid Lowering ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Pharmacological Agents ◽  
Beneficial Effects ◽  
Ppar Agonists ◽  
Energy Deprivation

Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that bind to DNA and regulate transcription of genes involved in lipid and glucose metabolism. A growing number of studies provide strong evidence that PPARs are the promising pharmacological targets for therapeutic intervention in various diseases including cardiovascular disorders caused by compromised energy metabolism. PPAR agonists have been widely used for decades as lipid-lowering and anti-inflammatory drugs. Existing studies are mainly focused on the anti-atherosclerotic effects of PPAR agonists; however, their role in the maintenance of cellular bioenergetics remains unclear. Recent studies on animal models and patients suggest that PPAR agonists can normalize lipid metabolism by stimulating fatty acid oxidation. These studies indicate the importance of elucidation of PPAR agonists as potential pharmacological agents for protection of the heart from energy deprivation. Here, we summarize and provide a comprehensive analysis of previous studies on the role of PPARs in the heart under normal and pathological conditions. In addition, the review discusses the PPARs as a therapeutic target and the beneficial effects of PPAR agonists, particularly bezafibrate, to attenuate cardiomyopathy and heart failure in patients and animal models.

scholarly journals Progress in Defining the Role of RSV in Allergy and Asthma: From Clinical Observations to Animal Models

2004 ◽  
Vol 11 (2) ◽  
pp. 113-119 ◽  
Author(s):  
W. V. Kalina ◽  
L. J. Gershwin
Keyword(s):  
Animal Models ◽  
Rna Virus ◽  
Allergic Sensitization ◽  
Upper Respiratory Tract ◽  
Young Infants ◽  
Wide Range ◽  
Similar Disease ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
The Impact

Respiratory syncytial virus (RSV), an RNA virus in the family Paramyxoviridae, causes respiratory disease in humans. A closely related bovine RSV is responsible for a remarkably similar disease syndrome in young cattle. Severe RSV disease is characterized by bronchiolitis. The impact of RSV on human health is demonstrated annually when infants are admitted to the hospital in large numbers. Nearly every child will have been infected with RSV by the age of 3 years. While the disease is most severe in young infants and elderly people, it can re-infect adults causing mild upper respiratory tract disease throughout life. In addition, there is growing evidence that RSV infection may also predispose some children to the development of asthma. This is based on the observation that children who wheeze with RSV-induced bronchiolitis are more likely to develop into allergic asthmatics. Recent studies describe attempts to create an RSV induced asthma model in mice and other species; these have shown some degree of success. Such reports of case studies and animal models have suggested a wide range of factors possibly contributing to RSV induced asthma, these include timing of RSV infection with respect to allergen exposure, prior allergic sensitization, environmental conditions, exposure to endotoxin, and the genetic background of the person or animal. Herein, we primarily focus on the influence of RSV infection and inhalation of extraneous substances (such as allergens or endotoxin) on development of allergic asthma.

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