scholarly journals Animal models in bicompatibility assessments of implants in soft and hard tissues

2021 ◽  
pp. 5-5
Author(s):  
Bogomir Prokic ◽  
Tijana Luzajic-Bozinovski ◽  
Vladimir Gajdov ◽  
Ivan Milosevic ◽  
Vera Todorovic ◽  
...  
Keyword(s):  
Cost Effective ◽  
Screening Tests ◽  
Laboratory Animals ◽  
In Vivo Models ◽  
Technological Advances ◽  
Hard Tissues ◽  
In Vivo Testing ◽  
Tissue Recovery ◽  
Eukaryotic Organisms

The ethical dilemmas of using animals as in vivo models in preclinical and clinical examinations have been increasingly present in recent decades. Small laboratory animals (rats, rabbits) will continue to be used because they are cost-effective and permit the formation of statistically testable cohort groups; a task that, for financial, maintenance and care reasons, is almost prohibitive for larger animals. Technological advances in the production of new biomaterials for clinical use are enormous, but screening tests and methods used to assess biocompatibility lag behind these advances. The assessment of biological responses is slow and based on millennial recovery mechanisms in eukaryotic organisms. Therefore, the goal of researchers in this field is to re-evaluate old methods of biocompatibility assessment and introduce new methods of evaluation, especially for in vivo testing. In that sense, a revision of the ISO standards was planned and conducted in 2017, which insisted on cytotoxicity testing in cell lines and produced concrete proposals on how biocompatibility should be quantified. In vivo biocompatibility evaluation of biomaterials used for soft tissue recovery commonly utilises rats. Rabbits are recommended for implants used for hard tissues, because of the rabbit?s size, the possibility of implanting the biomaterials on a larger bone surface, and because of the peculiarities of rabbit bone tissue that favours rapid recovery after bone defects and enables easy reading of the results.

scholarly journals THE ROLE OF IN VIVO MODELS IN PREDICTING TRANSDERMAL PERMEABILITY

2021 ◽  
Vol 91 (1) ◽  
pp. 86-98
Author(s):  
S. S. Malchenkova ◽  
◽  
N. S. Golyak ◽  
V. M. Tsarenkov ◽  
◽  
...  
Keyword(s):  
Structural Features ◽  
World Health ◽  
Laboratory Animals ◽  
Tape Stripping ◽  
In Vivo Models ◽  
Advantages And Disadvantages ◽  
Health Organization ◽  
Transdermal Permeability

The article presents the main types of laboratory animals that are used to study the transdermal permeability of chemical compounds. We described the structural features of epidermis, derma and skin appendages in humans and laboratory animals (small rodents, pigs, monkeys). We also emphasized advantages and disadvantages of various laboratory animals as objects for in vivo transdermal modeling. A method of extrapolation called “The parallelogram method” or «Triple Pack» has been singled out to predict the permeability of the human skin in the presence of experimental data on the permeability of the skin of animals in vivo and humans in vitro. The article describes the experimental design (including preparation of animals, premises and the substance applied) to determine transdermal permeability of substances in vivo under the guidelines of the World Health Organization and the Organization for Economic Cooperation and Development. Tissue microdialysis in volunteers has been identified as the most perfect and safest ways to promptly detect substances in the derma and tape stripping has been made in the cells of the stratum corneum.

scholarly journals Sea Buckthorn and Rosehip Oils with Chokeberry Extract to Prevent Hypercholesterolemia in Mice Caused by a High-Fat Diet In Vivo

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2941
Author(s):  
Lubov Tereshchuk ◽  
Kseniya Starovoytova ◽  
Olga Babich ◽  
Lyubov Dyshlyuk ◽  
Irina Sergeeva ◽  
...  
Keyword(s):  
Blood Serum ◽  
Dietary Supplement ◽  
Full Range ◽  
Antioxidant Properties ◽  
Hepatoprotective Activity ◽  
Sea Buckthorn ◽  
Biologically Active ◽  
Laboratory Animals ◽  
In Vivo Models

Dietary supplementation based on sea buckthorn and rosehip oils with added chokeberry extract was studied. We added the dietary supplement to the feed mixtures for laboratory animals. The possible toxicological effects and hypocholesterolemic, hepatoprotective activity of the dietary supplement in vivo were studied. After the observation period (6 weeks), no significant changes were found in the mass of organs and blood serum of laboratory animals (p > 0.05). However, there was a decrease in hypercholesterolemic indicators. Regular consumption of sea buckthorn and rosehip oils with added chokeberry extract (dietary supplement “ESB-1”) by laboratory animals inhibited the activity of liver enzymes and increased the antioxidant activity of blood serum (after the subcutaneous injection of sunflower oil/oil solution of carbon tetrachloride) but was not sufficient to bring them to physiological standards. The hypocholesterolemic and antioxidant properties of our dietary supplement already allow us to consider it a component of functional food products or a dietary supplement base. However, the full range of its biologically active properties, including the hepatoprotective function and regulation of metabolic disorders, has not been studied yet, which sets the direction of further research in vivo models and clinical practice to confirm its effectiveness in humans.

Synthetic Peptide Libraries: From Random Mixtures to In Vivo Testing

2020 ◽  
Vol 27 (6) ◽  
pp. 997-1016 ◽  
Author(s):  
Annamaria Sandomenico ◽  
Andrea Caporale ◽  
Nunzianna Doti ◽  
Simon Cross ◽  
Gabriele Cruciani ◽  
...  
Keyword(s):  
Synthetic Peptide ◽  
Peptide Libraries ◽  
Chemical Diversity ◽  
Bioactive Molecules ◽  
In Vivo Models ◽  
Lead Compounds ◽  
In Vivo Testing ◽  
Speed Up ◽  
New Compounds

Combinatorially generated molecular repertoires have been largely used to identify novel bioactive compounds. Ever more sophisticated technological solutions have been proposed to simplify and speed up such process, expanding the chemical diversity space and increasing the prospect to select new molecular entities with specific and potent activities against targets of therapeutic relevance. In this context, random mixtures of oligomeric peptides were originally used and since 25 years they represent a continuous source of bioactive molecules with potencies ranging from the sub-nM to microM concentration. Synthetic peptide libraries are still employed as starting “synthetic broths” of structurally and chemically diversified molecular fragments from which lead compounds can be extracted and further modified. Thousands of studies have been reported describing the application of combinatorial mixtures of synthetic peptides with different complexity and engrafted on diverse structural scaffolds for the identification of new compounds which have been further developed and also tested in in vivo models of relevant diseases. We briefly review some of the most used methodologies for library preparation and screening and the most recent case studies appeared in the literature where compounds have reached at least in vivo testing in animal or similar models. Recent technological advancements in biotechnology, engineering and computer science have suggested new options to facilitate the discovery of new bioactive peptides. In this instance, we anticipate here a new approach for the design of simple but focused tripeptide libraries against druggable cavities of therapeutic targets and its complementation with existing approaches.

scholarly journals Selective Eradication of Staphylococcus aureus by the Designer Genetically Programmed Yeast Biocontrol Agent

Antibiotics ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 527
Author(s):  
Sofiya O. Pipiya ◽  
Yuliana A. Mokrushina ◽  
Alexander G. Gabibov ◽  
Ivan V. Smirnov ◽  
Stanislav S. Terekhov
Keyword(s):  
Staphylococcus Aureus ◽  
Biocontrol Agent ◽  
Infectious Agent ◽  
Cost Effective ◽  
Biocontrol Agents ◽  
Alternative View ◽  
Ecological Niches ◽  
In Vivo Models ◽  
Conventional Antibiotics

Staphylococcus aureus is a common human pathogen that is particularly often associated with antibiotic resistance. The eradication of this ubiquitous infectious agent from its ecological niches and contaminated surfaces is especially complicated by excessive biofilm formation and persisting cells, which evade the antibacterial activity of conventional antibiotics. Here, we present an alternative view of the problem of specific S. aureus eradication. The constitutive heterologous production of highly specific bacteriolytic protease lysostaphin in yeast Pichia pastoris provides an efficient biocontrol agent, specifically killing S. aureus in coculture. A yeast-based anti-S. aureus probiotic was efficient in a high range of temperatures and target-to-effector ratios, indicating its robustness and versatility in eliminating S. aureus cells. The efficient eradication of S. aureus by live lysostaphin-producing P. pastoris was achieved at high scales, providing a simple, biocompatible and cost-effective strategy for S. aureus lysis in bioproduction and surface decontamination. Future biomedical applications based on designer yeast biocontrol agents require evaluation in in vivo models. However, we believe that this strategy is very promising since it provides highly safe, efficient and selective genetically programmed probiotics and targeted biocontrol agents.

scholarly journals Repurposing Licensed Drugs for Use Against Alzheimer’s Disease

2021 ◽  
pp. 1-12
Author(s):  
Leslie C. Norins
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Life Expectancy ◽  
Cost Effective ◽  
Epidemiological Data ◽  
Health Concern ◽  
Effective Manner ◽  
In Vivo Testing ◽  
Approved Drugs

Substantial evidence, composed of drug mechanisms of action, in vivo testing, and epidemiological data, exists to support clinical testing of FDA-approved drugs for repurposing to the treatment of Alzheimer’s disease (AD). Licensed compound investigation can often proceed at a faster and more cost-effective manner than un-approved compounds moving through the drug pipeline. As the prevalence of AD increases with life expectancy, the current rise in life expectancy amalgamated with the lack of an effective drug for the treatment of AD unnecessarily burdens our medical system and is an urgent public health concern. The unfounded reluctance to examine repurposing existing drugs for possible AD therapy further impedes the possibility of improving the quality of patient lives with a terminal disease. This review summarizes some evidence which exists to suggest certain already-approved drugs may be considered for the treatment of AD and will perhaps encourage physicians to off-label prescribe these safe therapeutics.

scholarly journals Comprehensive Evaluation of the Toxicity and Biosafety of Plasma Polymerized Nanoparticles

Nanomaterials ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1176
Author(s):  
Praveesuda L. Michael ◽  
Yuen Ting Lam ◽  
Juichien Hung ◽  
Richard P. Tan ◽  
Miguel Santos ◽  
...  
Keyword(s):  
Comprehensive Evaluation ◽  
Cost Effective ◽  
Cell Types ◽  
Repeated Injection ◽  
In Vivo Models ◽  
Intravenous Injections ◽  
Cost Effective Alternative ◽  
High Doses

The rapid growth of nanoparticle-based therapeutics has underpinned significant developments in nanomedicine, which aim to overcome the limitations imposed by conventional therapies. Establishing the safety of new nanoparticle formulations is the first important step on the pathway to clinical translation. We have recently shown that plasma-polymerized nanoparticles (PPNs) are highly efficient nanocarriers and a viable, cost-effective alternative to conventional chemically synthesized nanoparticles. Here, we present the first comprehensive toxicity and biosafety study of PPNs using both established in vitro cell models and in vivo models. Overall, we show that PPNs were extremely well tolerated by all the cell types tested, significantly outperforming commercially available lipid-based nanoparticles (lipofectamine) used at the manufacturer’s recommended dosage. Supporting the in vitro data, the systemic toxicity of PPNs was negligible in BALB/c mice following acute and repeated tail-vein intravenous injections. PPNs were remarkably well tolerated in mice without any evidence of behavioral changes, weight loss, significant changes to the hematological profile, or signs of histological damage in tissues. PPNs were tolerated at extremely high doses without animal mortality observed at 6000 mg/kg and 48,000 mg/kg for acute and repeated-injection regimens, respectively. Our findings demonstrate the safety of PPNs in biological systems, adding to their future potential in biomedical applications.

Establishment of a chordoma xenograft and in vivo testing of compounds identified by high-throughput screening.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10025-10025
Author(s):  
Matteo Maria Trucco ◽  
Breelyn A. Wilky ◽  
Ola Awad ◽  
Preeti Shah ◽  
Naheed Gul ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Cell Lines ◽  
High Throughput ◽  
High Throughput Screening ◽  
Xenograft Model ◽  
Dramatic Reduction ◽  
In Vivo Models ◽  
Drug Concentrations ◽  
In Vivo Testing

10025 Background: Chordoma is a rare primary bone malignancy that arises in the skull base, spine and sacrum and originates from remnants of the notochord. Therapy primarily consists of surgical resection and radiation. These tumors are typically resistant to conventional chemotherapy, and to date there are no FDA-approved agents for chordoma. The lack of in vivo models of chordoma has impeded the development of new therapies for this tumor. Methods: Primary tumor from a classic sacral chordoma was obtained, immediately processed into a single cell suspension and injected in to the parasacral area of a NOD/SCID/IL-2R gamma-null mouse, and tumor grew after 3 months. The NIH Chemical Genomics Center performed high-throughput screening of 2,816 compounds. Two established chordoma cell lines, U-CH1 and UCH2B, were treated and cell viability measured by CellTiter-Glo assay. Cells were incubated for 48 hours with drug concentrations ranging from 0.5nM to 46uM. The screen yielded several compounds that showed activity and two were tested in the xenograft. Results: We have established a xenograft model of dedifferentiated chordoma. High-throughput screening of compounds identified compounds that show activity against chordoma cell lines. In vivo testing of two identified compounds showed a dramatic reduction of tumor growth. Conclusions: We have established a xenograft model of dedifferentiated chordoma. High-throughput screening of compounds identified compounds that show activity against chordoma cell lines. In vivo testing of two identified compounds showed a dramatic reduction of tumor growth.

scholarly journals Biogenic Ferrihydrite Nanoparticles: Synthesis, Properties In Vitro and In Vivo Testing and the Concentration Effect

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 323
Author(s):  
Sergey V. Stolyar ◽  
Oksana A. Kolenchukova ◽  
Anna V. Boldyreva ◽  
Nadezda S. Kudryasheva ◽  
Yulia V. Gerasimova ◽  
...  
Keyword(s):  
Klebsiella Oxytoca ◽  
The Body ◽  
Blocking Temperature ◽  
Laboratory Animals ◽  
High Dispersion ◽  
Intracellular Regeneration ◽  
Minimum Concentration ◽  
In Vivo Testing

Biogenic ferrihydrite nanoparticles were synthesized as a result of the cultivation of Klebsiella oxytoca microorganisms. The distribution of nanoparticles in the body of laboratory animals and the physical properties of the nanoparticles were studied. The synthesized ferrihydrite nanoparticles are superparamagnetic at room temperature, and the characteristic blocking temperature is 23–25 K. The uncompensated moment of ferrihydrite particles was determined to be approximately 200 Bohr magnetons. In vitro testing of different concentrations of ferrihydrite nanoparticles for the functional activity of neutrophilic granulocytes by the chemiluminescence method showed an increase in the release of primary oxygen radicals by blood phagocytes when exposed to a minimum concentration and a decrease in secondary radicals when exposed to a maximum concentration. In vivo testing of ferrihydrite nanoparticles on Wister rats showed that a suspension of ferrihydrite nanoparticles has chronic toxicity, since it causes morphological changes in organs, mainly in the spleen, which are characterized by the accumulation of hemosiderin nanoparticles (stained blue according to Perls). Ferrihydrite can also directly or indirectly stimulate the proliferation and intracellular regeneration of hepatocytes. The partial detection of Perls-positive cells in the liver and kidneys can be explained by the rapid elimination from organs and the high dispersion of the nanomaterial. Thus, it is necessary to carry out studies of these processes at the systemic level, since the introduction of nanoparticles into the body is characterized by adaptive-proliferative processes, accompanied by the development of cell dystrophy and tension of the phagocytic system.

scholarly journals TopoDB: a novel multifunctional management system for laboratory animal colonies

Database ◽  
2020 ◽  
Vol 2020 ◽  
Author(s):  
Adam Renschen ◽  
Atsuko Matsunaga ◽  
Jorge R Oksenberg ◽  
Adam Santaniello ◽  
Alessandro Didonna
Keyword(s):  
Therapeutic Potential ◽  
Basic Research ◽  
Inbred Strains ◽  
Laboratory Animals ◽  
Phenotypic Data ◽  
In Vivo Models ◽  
Web Based ◽  
Rational Management ◽  
Biological Environment

Abstract Animal models are widely employed in basic research to test mechanistic hypotheses in a complex biological environment as well as to evaluate the therapeutic potential of candidate compounds in preclinical settings. Rodents, and in particular mice, represent the most common in vivo models for their small size, short lifespan and possibility to manipulate their genome. Over time, a typical laboratory will develop a substantial number of inbred strains and transgenic mouse lines, requiring a substantial effort, in both logistic and economic terms, to maintain an animal colony for research purposes and to safeguard the integrity of results. To meet this need, here we present TopoDB, a robust and extensible web-based platform for the rational management of laboratory animals. TopoDB allows an easy tracking of individual animals within the colony and breeding protocols as well as the convenient storage of both genetic and phenotypic data generated in the different experiments. Altogether, these features facilitate and enhance the design of in vivo research, thus reducing the number of necessary animals and the housing costs. In summary, TopoDB represents a novel valuable tool in modern biomedical research. Database URL: https://github.com/UCSF-MS-DCC/TopoDB

scholarly journals Compared Anatomy and Histology between Mus musculus Mice (Swiss) and Rattus norvegicus Rats (Wistar)

2019 ◽  
Author(s):  
Giorgio Silva-Santana ◽  
Fábio Aguiar-Alves ◽  
Licínio Esmeraldo Silva ◽  
Maria Lúcia Barreto ◽  
Jemima Fuentes Ribeiro Silva ◽  
...  
Keyword(s):  
Mus Musculus ◽  
Rattus Norvegicus ◽  
Experimental Studies ◽  
Alternative Methods ◽  
Laboratory Animals ◽  
Surgical Interventions ◽  
Technological Advances ◽  
Prophylactic Measures

The evolution of knowledge in biological and medical areas which made possible scientific and technological advances are attributed to anatomical studies, physiology and immunology in animals, contributing to the discovery of prophylactic measures and treatments of diseases that affect humans and animals. Currently, substitution is suggested by alternative methods that do not use laboratory animals, however in vitro methods may never be able to provide similar results to in vivo methods. Mice and rats are the most used animals in experimental researches, the anatomical, histological and genetic differences between species should be carefully evaluated, to better apply the study model and avoid unnecessary waste avoid. This study, aimed at an anatomical comparative and histological relationship between a rat´s and a mouse´s organs, is of great importance in experimental studies. For such, 30 Mus musculus (Swiss) mice and 15 Rattus norvegicus (Wistar) male and heterogenic rats, were used. All animals were kept free of pathogenic microorganisms, with the absence of surgical interventions that could cause anatomical and physiological changes. It was possible to observe significant anatomical and histological differences between spleens, brains, hearts, stomachs and intestines, livers, eyes, lungs and kidneys among species, which will serve as a basis to assist in choosing the most satisfactory research model. Few studies relate specific characteristics among laboratory animals, being restricted to a few veterinary and zoology books. The greater the organic, physiological and anatomical similarities are with the human being, the greater is the applicability of the animals in studies. However, it is not possible to lay down general rules to validate the extrapolation from one species to another.

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