News Article | April 26, 2017
Amsterdam, The Netherlands, April 26, 2017 - The use of animals in biomedical research has long been the focus of campaigns by animal rights activists. Two leading scientists writing in the European Journal of Internal Medicine give their expert view of the importance of animal testing to medical progress and present ways it could be further improved to yield more useful clinical results. "It cannot be stressed enough that animal studies have led to the production of drugs that have affected the epidemiology of human pathology, contributing to prolonging life. There is no magic formula at present to predict - at the preclinical level - the therapeutic value of a drug for people with a disease. Preclinical studies are needed in order to formulate hypotheses that justify clinical trials. Without these preliminary in vitro and in vivo studies in selected animal species, it would be unethical to test still unproven chemicals in humans," explains Silvio Garattini, MD, Founder and Director of the Mario Negri Institute for Pharmacological Research, Milan, Italy. His co-author, Giuliano Grignaschi, PhD, head of the Animal Care Unit at the Mario Negri Institute and vice president of the Basel Declaration Society in Switzerland, which promotes information about animal testing, adds that "the pressure of public opinion, particularly of organized groups of 'animalists,' obliges preclinical and clinical scientists to come out of their 'ivory tower' to explain the complexity of translating research results from animals to man." Vaccines against poliomyelitis, meningitis, and rotaviruses are excellent examples in which animal testing, and the translation from animals to man, have proved effective, as are a number of antibiotics and the recent agents against HIV and hepatitis C viruses. However, the authors acknowledge that at the other extreme, there have been poor correlations between results in animals and man in several diseases such as stroke, amyotrophic lateral sclerosis (ALS), and Alzheimer's disease, and they summarize several analyses that have set out to understand why results in animals and man differ in these cases. The authors present four ways in which animal experiments could be improved in order to increase their probability of predicting useful clinical results. First, studies need to be intensified and techniques developed to improve and reduce the use of animals following the 3R rule (Replace, Reduce, and Refine). These guiding principles underpin the humane use of animals in scientific research and any researcher planning to use animals in their research must first show why there is no alternative and what will be done to minimize numbers and suffering, Second, rules developed to improve clinical trials should be incorporated into animal testing to minimize bias. Third, research is needed to improve the translation of animal research to patients, they argue, pointing out that the National Institutes of Health (NIH) in the U.S. has recently launched a program to train preclinical scientists to plan their experimental trials better by applying the same rules as for clinical trials. "There is, however, a pressing need for responsibility in the scientific community, not only among scientists, but also in the editorial boards of journals and funding bodies to focus more on the quality of articles and research proposals dealing with animal investigation," they note. Fourth, once bias has been taken care of, difficulties remain for each specific demand for therapy - symptomatic, preventive, or curative - of finding the animal species that best mimics the human condition. Animals with specific pathology such as diabetes, high cholesterol, and hypertension have helped scientists develop antidiabetic, hypocholesterolemic, and antihypertensive drugs, which have been effective in man and are widely used. More studies are needed in aged animals to mimic the condition of elderly people with co-morbidities that require several drugs. Different chemical mediators may be important tools for discovering new drugs once they have been found to exert similar effects in a given animal species and man. "Limitations to the use of animals, particularly other than rodents, are an obstacle to obtaining a wider spectrum of activity across species which may help in deciding when a treatment is suitable for patients," says Dr Grignaschi. "Nevertheless, there is room for substantial improvement in the protocols of animal tests to boost their credibility and reproducibility. "For the time being, animal models remain the best alternative given the limited usefulness of computer and in vitro models, and their use must continue, considering that patients cannot just wait for better tests to cure their suffering," concludes Prof. Garattini.
Brunelli R.L.,Mind and Behavior Unit |
Brunelli R.L.,Animal Behavior Graduate Group |
Blake J.,Animal Care Unit |
Willits N.,University of California at Davis |
And 2 more authors.
Journal of the American Association for Laboratory Animal Science | Year: 2014
Nursery-reared infants have several behavioral and physiologic differences from their mother-reared counterparts. We investigated whether a response-contingent surrogate mitigated some of those differences by decreasing fearfulness and partner-clinging and increasing environmental exploration in nursery-reared infants continuously paired with a peer. Six nursery-reared infant rhesus macaques (in pairs) were given a mechanical responsive surrogate (RS), and 6 (in pairs) were given an identical but nonresponsive surrogate (NRS). The 2 treatment groups were compared and then combined into a single group of all 12 of surrogate-exposed animals (CS) that was compared with a nonsurrogate control group (NS) of 10 nursery-reared infants. Results showed significant differences between CS and NS infants but no significant differences between the RS and NRS infants. As compared with NS infants, CS infants showed less partner-clinging, less affiliation directed toward only partner, and more foraging and tactile-oral exploration of the environment. These advantageous effects support additional research to develop improved surrogate and the implementation of surrogate programs for nursery-reared infants. Copyright 2014 by the American Association for Laboratory Animal Science
Capolla S.,University of Trieste |
Garrovo C.,Institute for Maternal and Child Health IRCCS Burlo Garofolo |
Zorzet S.,University of Trieste |
Lorenzon A.,Animal care Unit |
And 8 more authors.
International Journal of Nanomedicine | Year: 2015
The expectations of nanoparticle (NP)-based targeted drug delivery systems in cancer, when compared with convectional therapeutic methods, are greater efficacy and reduced drug side effects due to specific cellular-level interactions. However, there are conficting literature reports on enhanced tumor accumulation of targeted NPs, which is essential for translating their applications as improved drug-delivery systems and contrast agents in cancer imaging. In this study, we characterized biodegradable NPs conjugated with an anti-CD20 antibody for in vivo imaging and drug delivery onto tumor cells. NPs’ binding specificity mediated by anti-CD20 antibody was evaluated on MEC1 cells and chronic lymphocytic leukemia patients’ cells. The whole-body distribution of untargeted NPs and anti-CD20 NPs were compared by time-domain optical imaging in a localized human/mouse model of B-cell malignancy. These studies provided evidence that NPs’ functionalization by an anti-CD20 antibody improves tumor pharmacoki-netic profiles in vivo after systemic administration and increases in vivo imaging of tumor mass compared to non-targeted NPs. Together, drug delivery and imaging probe represents a promising theranostics tool for targeting B-cell malignancies. © 2015 Capolla et al.
PubMed | Mind and Behavior Unit, Animal Care Unit and University of California at Davis
Type: Journal Article | Journal: Journal of the American Association for Laboratory Animal Science : JAALAS | Year: 2014
Nursery-reared infants have several behavioral and physiologic differences from their mother-reared counterparts. We investigated whether a response-contingent surrogate mitigated some of those differences by decreasing fearfulness and partner-clinging and increasing environmental exploration in nursery-reared infants continuously paired with a peer. Six nursery-reared infant rhesus macaques (in pairs) were given a mechanical responsive surrogate (RS), and 6 (in pairs) were given an identical but nonresponsive surrogate (NRS). The 2 treatment groups were compared and then combined into a single group of all 12 of surrogate-exposed animals (CS) that was compared with a nonsurrogate control group (NS) of 10 nursery-reared infants. Results showed significant differences between CS and NS infants but no significant differences between the RS and NRS infants. As compared with NS infants, CS infants showed less partner-clinging, less affiliation directed toward only partner, and more foraging and tactile-oral exploration of the environment. These advantageous effects support additional research to develop improved surrogate and the implementation of surrogate programs for nursery-reared infants.
Zuniga-Toala A.,National Autonomous University of Mexico |
Zatarain-Barron Z.L.,National Institute of Medical science and Nutrition Salvador Zubiran |
Hernandez-Pando R.,National Institute of Medical science and Nutrition Salvador Zubiran |
Negrette-Guzman M.,National Autonomous University of Mexico |
And 5 more authors.
Phytomedicine | Year: 2013
It has been shown that the pretreatment with nordihydroguaiaretic acid (NDGA), a lignan with direct and indirect antioxidant properties, protects against the ischemia-reperfusion (I/R)-induced renal oxidant damage. Although it has been shown that NDGA induces Nrf2 nuclear translocation in renal epithelial LLC-PK1 cells in culture, it is unknown if NDGA may induce Nrf2 translocation in vivo. In this work was explored if NDGA is able to induce in vivo Nrf2 nuclear translocation in kidneys of rats submitted to uni-nephrectomy (U-NX) or I/R injury. Four groups of male Wistar rats were used: U-NX, NDGA, I/R, and I/R + NDGA. NDGA was injected i.p. (10 mg/kg/day) starting 48 h before I/R. Kidney samples were obtained at 3 h of reperfusion after to measure Nrf2 translocation. Additional groups of rats were studied at 24 h of reperfusion to measure histological damage and apoptosis. NDGA was able to induce Nrf2 translocation in vivo in kidneys of rats submitted to both U-NX and I/R injury and to protect against renal histological damage and apoptosis. It is concluded that the pretreatment of NDGA is able to induce in vivo nuclear Nrf2 translocation in kidney of rats suggesting that this may be involved in the renoprotection against I/R. © 2013 Elsevier GmbH.
A novel fusion protein-based vaccine comprising a cell penetrating and immunostimulatory peptide linked to human papillomavirus (HPV) type 16 E7 antigen generates potent immunologic and anti-tumor responses in mice
Granadillo M.,Center for Genetic Engineering and Biotechnology |
Vallespi M.G.,Center for Genetic Engineering and Biotechnology |
Batte A.,Center for Genetic Engineering and Biotechnology |
Mendoza O.,Animal Care Unit |
And 3 more authors.
Vaccine | Year: 2011
The ultimate success of cancer vaccination is dependent upon the generation of tumor-specific CTLs. In this study, we designed and evaluated a novel fusion protein comprising a cell penetrating and immunostimulatory peptide corresponding to residues 32-51 of the Limulus polyphemus protein (LALF32-51) linked to human papillomavirus (HPV) 16 E7 antigen (LALF32-51-E7). We demonstrated that LALF32-51 penetrates the cell membrane and delivers E7 into cells. In a preclinical model of HPV16-induced cervical carcinoma we showed that vaccination with adjuvant-free LALF32-51-E7 fusion protein significantly improves the presentation of E7-derived peptides to T-cells in vitro and induces suppression of tumor growth. © 2010 Elsevier Ltd.