scholarly journals Approaching 3R teaching in biomedical engineering

2020 ◽  
Author(s):  
Valeria Chiono
Keyword(s):  
Animal Models ◽  
Biomedical Engineering ◽  
Experimental Models ◽  
Preclinical Testing ◽  
Preclinical Trials ◽  
European Standards ◽  
Preclinical Animal Models ◽  
In Silico Models

Since its adhesion to Centro3R, Politecnico di Torino has approached 3R teaching through a new Master course, entitled “New advances in alternative preclinical trials”. This is a multidisciplinary optional course for Master students in Biomedical Engineering, with the contribution of different teachers, who are experts on different aspects of preclinical testing of biomedical devices: European Standards for preclinical experimentation; preclinical animal models; protection of animal welfare in the European legislation; the role of statistics on the application of the 3R principle; preclinical experimental models in vitro; in silico models. This contribution describes the subjects faced by the course and their importance in the context of the 3R Principle.

scholarly journals Septopremaxillary ligament traction system: a review

2019 ◽  
Vol 6 (4) ◽  
pp. 1363
Author(s):  
Rajani R. Elayadath ◽  
Biswas P. Palakunnu
Keyword(s):  
Systematic Review ◽  
Animal Models ◽  
Animal Studies ◽  
Experimental Models ◽  
Human Condition ◽  
System A ◽  
Biomechanical Force ◽  
Traction System

Over the years, several animal studies have been conducted concerning the role of cartilaginous nasal septum, septopremaxillary ligament in midfacial growth. Most of the studies utilized non primate animal models at first and then more recently in primates such as chimpanzee. Proper choice of animal model to extrapolate from is critical for successful experimental design. Although nonhuman primates are phylogenetically closer to humans than other mammalian groups for better extrapolation to human condition, not all the craniofacial experiments require primate models. Renewed interests in understanding the influence of septopremaxillary ligament resection on midfacial growth led to many in vitro experiments on animal models. Recently systematic review of relevant animal experiment is regarded as a prerequisite for the conduct of the new clinical trials. Despite this fact, the literature addressing this topic in humans and systematic review on the effect of the septopremaxillary ligament is scarce. The more recent studies show that the maxillary labial frenum encloses the septopremaxillary ligament and forms an important constituent of septopremaxillary traction system. The biomechanical force mediating through the septopremaxillary ligament, maxillary labial frenum and nasolabial muscles results in stimulating their effects on sagital growth of the maxilla. The main purpose of this review is to update and extend the knowledge of the role of septopremaxillary traction system on the midfacial growth by synthesizing the available literature involving the septopremaxillary ligament resection in experimental models. If this review could synthesize the results of relevant research, a change in the therapeutic notions can also be expected.

Bioengineered in vitro Vascular Models for Applications in Interventional Radiology

2019 ◽  
Vol 24 (45) ◽  
pp. 5367-5374 ◽  
Author(s):  
Xiaoyun Li ◽  
Seyed M. Moosavi-Basri ◽  
Rahul Sheth ◽  
Xiaoying Wang ◽  
Yu S. Zhang
Keyword(s):  
Interventional Radiology ◽  
Animal Models ◽  
Blood Vessels ◽  
In Vitro Models ◽  
The Past ◽  
Endovascular Interventions ◽  
Conventional Animal ◽  
Vascular Structures

The role of endovascular interventions has progressed rapidly over the past several decades. While animal models have long-served as the mainstay for the advancement of this field, the use of in vitro models has become increasingly widely adopted with recent advances in engineering technologies. Here, we review the strategies, mainly including bioprinting and microfabrication, which allow for fabrication of biomimetic vascular models that will potentially serve to supplement the conventional animal models for convenient investigations of endovascular interventions. Besides normal blood vessels, those in diseased states, such as thrombosis, may also be modeled by integrating cues that simulate the microenvironment of vascular disorders. These novel engineering strategies for the development of biomimetic in vitro vascular structures will possibly enable unconventional means of studying complex endovascular intervention problems that are otherwise hard to address using existing models.

scholarly journals Role of the C5a-C5a receptor axis in the inflammatory responses of the lungs after experimental polytrauma and hemorrhagic shock

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shinjini Chakraborty ◽  
Veronika Eva Winkelmann ◽  
Sonja Braumüller ◽  
Annette Palmer ◽  
Anke Schultze ◽  
...  
Keyword(s):  
Hemorrhagic Shock ◽  
Inflammatory Responses ◽  
Experimental Models ◽  
Lung Damage ◽  
C5a Receptor ◽  
Cytokine Levels ◽  
Vitro Model

AbstractSingular blockade of C5a in experimental models of sepsis is known to confer protection by rescuing lethality and decreasing pro-inflammatory responses. However, the role of inhibiting C5a has not been evaluated in the context of sterile systemic inflammatory responses, like polytrauma and hemorrhagic shock (PT + HS). In our presented study, a novel and highly specific C5a L-aptamer, NoxD21, was used to block C5a activity in an experimental murine model of PT + HS. The aim of the study was to assess early modulation of inflammatory responses and lung damage 4 h after PT + HS induction. NoxD21-treated PT + HS mice displayed greater polymorphonuclear cell recruitment in the lung, increased pro-inflammatory cytokine levels in the bronchoalveolar lavage fluids (BALF) and reduced myeloperoxidase levels within the lung tissue. An in vitro model of the alveolar-capillary barrier was established to confirm these in vivo observations. Treatment with a polytrauma cocktail induced barrier damage only after 16 h, and NoxD21 treatment in vitro did not rescue this effect. Furthermore, to test the exact role of both the cognate receptors of C5a (C5aR1 and C5aR2), experimental PT + HS was induced in C5aR1 knockout (C5aR1 KO) and C5aR2 KO mice. Following 4 h of PT + HS, C5aR2 KO mice had significantly reduced IL-6 and IL-17 levels in the BALF without significant lung damage, and both, C5aR1 KO and C5aR2 KO PT + HS animals displayed reduced MPO levels within the lungs. In conclusion, the C5aR2 could be a putative driver of early local inflammatory responses in the lung after PT + HS.

scholarly journals From animal models to patients: the role of placental microRNAs, miR-210, miR-126, and miR-148a/152 in preeclampsia

2020 ◽  
Vol 134 (8) ◽  
pp. 1001-1025 ◽  
Author(s):  
Sonya Frazier ◽  
Martin W. McBride ◽  
Helen Mulvana ◽  
Delyth Graham
Keyword(s):  
Animal Models ◽  
Cell Types ◽  
Rodent Model ◽  
Hypertensive Disorder ◽  
Model Studies ◽  
Genetic Components ◽  
Immune Mediated ◽  
Hypertensive Disorder Of Pregnancy

Abstract Placental microRNAs (miRNAs) regulate the placental transcriptome and play a pathological role in preeclampsia (PE), a hypertensive disorder of pregnancy. Three PE rodent model studies explored the role of placental miRNAs, miR-210, miR-126, and miR-148/152 respectively, by examining expression of the miRNAs, their inducers, and potential gene targets. This review evaluates the role of miR-210, miR-126, and miR-148/152 in PE by comparing findings from the three rodent model studies with in vitro studies, other animal models, and preeclamptic patients to provide comprehensive insight into genetic components and pathological processes in the placenta contributing to PE. The majority of studies demonstrate miR-210 is upregulated in PE in part driven by HIF-1α and NF-κBp50, stimulated by hypoxia and/or immune-mediated processes. Elevated miR-210 may contribute to PE via inhibiting anti-inflammatory Th2-cytokines. Studies report an up- and downregulation of miR-126, arguably reflecting differences in expression between cell types and its multifunctional capacity. MiR-126 may play a pro-angiogenic role by mediating the PI3K-Akt pathway. Most studies report miR-148/152 family members are upregulated in PE. Evidence suggests they may inhibit DNA methylation of genes involved in metabolic and inflammatory pathways. Given the genetic heterogeneity of PE, it is unlikely that a single placental miRNA is a suitable therapeutic target for all patients. Investigating miRNAs in PE subtypes in patients and animal models may represent a more appropriate approach going forward. Developing methods for targeting placental miRNAs and specific placental cell types remains crucial for research seeking to target placental miRNAs as a novel treatment for PE.

scholarly journals The Role of Carrageenan in Inflammatory Bowel Diseases and Allergic Reactions: Where Do We Stand?

Nutrients ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 3402
Author(s):  
Barbara Borsani ◽  
Raffaella De Santis ◽  
Veronica Perico ◽  
Francesca Penagini ◽  
Erica Pendezza ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Experimental Models ◽  
Gelling Agent ◽  
Current Evidence ◽  
Allergic Reactions ◽  
Processed Foods ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Carrageenan (CGN) is a high molecular weight polysaccharide extracted from red seaweeds, composed of D-galactose residues linked in β-1,4 and α-1,3 galactose-galactose bond, widely used as a food additive in processed foods for its properties as a thickener, gelling agent, emulsifier, and stabilizer. In recent years, with the spread of the Western diet (WD), its consumption has increased. Nonetheless, there is a debate on its safety. CGN is extensively used as an inflammatory and adjuvant agent in vitro and in animal experimental models for the investigation of immune processes or to assess the activity of anti-inflammatory drugs. CGN can activate the innate immune pathways of inflammation, alter the gut microbiota composition and the thickness of the mucus barrier. Clinical evidence suggests that CGN is involved in the pathogenesis and clinical management of inflammatory bowel diseases (IBD), indeed food-exclusion diets can be an effective therapy for disease remission. Moreover, specific IgE to the oligosaccharide α-Gal has been associated with allergic reactions commonly referred to as the “α-Gal syndrome”. This review aims to discuss the role of carrageenan in inflammatory bowel diseases and allergic reactions following the current evidence. Furthermore, as no definitive data are available on the safety and the effects of CGN, we suggest gaps to be filled and advise to limit the human exposure to CGN by reducing the consumption of ultra-processed foods.

scholarly journals Integrating Animal Models and In Vitro Tissue Models to Elucidate the Role of Desmosomal Proteins in Diseases

2014 ◽  
Vol 21 (1) ◽  
pp. 55-63 ◽  
Author(s):  
Maranke I. Koster ◽  
Jason Dinella ◽  
Jiangli Chen ◽  
Charlene O’Shea ◽  
Peter J. Koch
Keyword(s):  
Animal Models ◽  
Tissue Models

scholarly journals The evolution of strategies to minimise the risk of human drug-induced liver injury (DILI) in drug discovery and development

2020 ◽  
Vol 94 (8) ◽  
pp. 2559-2585 ◽  
Author(s):  
Paul A. Walker ◽  
Stephanie Ryder ◽  
Andrea Lavado ◽  
Clive Dilworth ◽  
Robert J. Riley
Keyword(s):  
Drug Discovery ◽  
Liver Injury ◽  
Drug Uptake ◽  
Drug Induced ◽  
Drug Induced Liver Injury ◽  
New Chemical Entities ◽  
Preclinical Animal Models ◽  
Uptake Transporters

Abstract Early identification of toxicity associated with new chemical entities (NCEs) is critical in preventing late-stage drug development attrition. Liver injury remains a leading cause of drug failures in clinical trials and post-approval withdrawals reflecting the poor translation between traditional preclinical animal models and human clinical outcomes. For this reason, preclinical strategies have evolved over recent years to incorporate more sophisticated human in vitro cell-based models with multi-parametric endpoints. This review aims to highlight the evolution of the strategies adopted to improve human hepatotoxicity prediction in drug discovery and compares/contrasts these with recent activities in our lab. The key role of human exposure and hepatic drug uptake transporters (e.g. OATPs, OAT2) is also elaborated.

Evidence for the Usefulness of in vitro Dialyzability, Caco-2 Cell Models, Animal Models, and Algorithms to Predict Zinc Bioavailability in Humans

2005 ◽  
Vol 75 (6) ◽  
pp. 423-435 ◽  
Author(s):  
Christine Hotz
Keyword(s):  
Animal Models ◽  
Experimental Models ◽  
Dietary Factors ◽  
Human Organism ◽  
Zinc Absorption ◽  
In Vitro Methods ◽  
Zinc Bioavailability ◽  
Zinc Retention ◽  
The Impact

Low bioavailability of zinc in certain diet types may contribute to zinc deficiency and its consequences in populations. As a result, several experimental models including animal models, in vitro dialyzability models, and Caco-2 cells, have been used to study these factors and estimate their impact on human zinc absorption. For the most part, consistency has been observed between the latter models and human absorption studies to identify factors that enhance or inhibit zinc bioavailability. However, dialyzability methods are limited to modeling luminal interactions among the factors as they affect zinc availability while Caco-2 cells can model luminal effects and uptake by intestinal cells. Neither animal nor in vitro methods can predict the magnitude of zinc absorption at the level of the human organism. Caco-2 cells will be useful models for understanding the mechanisms of intestinal zinc absorption. The in vitro methods are also limited to modeling absorption and the interactions that occur. Algorithms to estimate zinc absorption, based on dietary content of zinc absorption modifiers, have been derived from human studies. An algorithm derived from studies of zinc retention from radioactive zinc-labeled test meals underestimates zinc absorption compared to that derived from measurement of true zinc absorption from total diets using isotopic tracer methods. Based on the latter, phytate appears to be the only major inhibitor of zinc absorption from typical diets. Ultimately, population-based studies are needed to determine the impact of dietary factors that modulate zinc absorption on the adequacy of zinc status.

Protein degradation: a validated therapeutic strategy with exciting prospects

2017 ◽  
Vol 61 (5) ◽  
pp. 517-527 ◽  
Author(s):  
Honorine Lebraud ◽  
Tom D. Heightman
Keyword(s):  
Animal Models ◽  
Protein Degradation ◽  
Small Molecules ◽  
Cancer Patients ◽  
Clinical Efficacy ◽  
Therapeutic Strategy ◽  
Substrate Recognition ◽  
Pharmacological Targets ◽  
Preclinical Animal Models

In a time of unprecedented challenges in developing potent, selective and well-tolerated protein inhibitors as therapeutics, drug hunters are increasingly seeking alternative modalities to modulate pharmacological targets. Selective inhibitors are achievable for only a fraction of the proteome, and are not guaranteed to elicit the desired response in patients, especially when pursuing targets identified through genetic knockdown. Targeted protein degradation holds the potential to expand the range of proteins that can be effectively modulated. Drugs inducing protein degradation through misfolding or by modulating cereblon (CRBN) substrate recognition are already approved for treatment of cancer patients. The last decade has seen the development of proteolysis targeting chimeras (PROTACs), small molecules that elicit proteasomal degradation by causing protein polyubiquitination. These have been used to degrade a range of disease-relevant proteins in cells, and some show promising efficacy in preclinical animal models, although their clinical efficacy and tolerability is yet to be proven. This review introduces current strategies for protein degradation with an emphasis on PROTACs and the role of click chemistry in PROTAC research through the formation of libraries of preclicked PROTACs or in-cell click-formed PROTACs (CLIPTACs).

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