Opinion on the Use of Animal Models in Nonclinical Safety Assessment: Pros and Cons

2021 ◽  
pp. 019262332110034
Author(s):  
Radhakrishna Sura ◽  
Julie Hutt ◽  
Sherry Morgan
Keyword(s):  
Animal Models ◽  
Safety Assessment ◽  
Critical Role ◽  
Human Health Risks ◽  
Safety Risks ◽  
New Chemical Entities ◽  
Impact Risk ◽  
Potential Benefits ◽  
Pros And Cons ◽  
Human Specific

Nonclinical evaluation of human safety risks for new chemical entities (NCEs) is primarily conducted in conventional healthy animals (CHAs); however, in certain instances, animal models of diseases (AMDs) can play a critical role in the understanding of human health risks. Animal models of diseases may be especially important when there is a need to understand how disease conditions associated with the intended indication might impact risk assessment of NCEs or when CHAs lack the human-specific target of interest (receptor, etc). Although AMDs have potential benefits over CHAs, they also have limitations. Understanding these limitations and optimizing the AMDs of interest should be done prior to proceeding with studies that will guide development of NCE. The purpose of this manuscript is to provide an overview of the major pros and cons of utilization of AMDs in nonclinical safety assessment.

Healthcare supply chain management: literature review and some issues

2018 ◽  
Vol 15 (3) ◽  
pp. 265-287 ◽  
Author(s):  
Bhavana Mathur ◽  
Sumit Gupta ◽  
Makhan Lal Meena ◽  
G.S. Dangayach
Keyword(s):  
Supply Chain ◽  
Supply Chain Management ◽  
Literature Review ◽  
Organizational Performance ◽  
Critical Role ◽  
Sample Survey ◽  
Future Research ◽  
Chain Management ◽  
Content Type ◽  
Potential Benefits

PurposeThe purpose of this paper is to examine the causal linkages among supply chain practices, effectiveness of supply chain performance (SCP) and organizational performance (OP) in Indian healthcare industries.Design/methodology/approachThis paper is helpful in developing a framework for linking a healthcare supply chain practice to its OP, and thus identifies how such a linkage can be connected to the effectiveness of SCP. Such effort also enables the authors to derive a set of recommended supply chain practices for SC performance.FindingsFrom the literature review, this paper finds that, in the context of Indian healthcare industries, efficient SC performance may play a critical role for overall OP improvement, as there is a close interrelationship between supply chain management (SCM) practices and SCP that may have a more significant effect on OP improvement.Research limitations/implicationsThe principle limitation of the paper is that it is performed only in a particular industry and with a questionnaire survey which could be extended in future for other industries also. Another limitation of the paper is that it is focused only on the SCP of medical device and equipment supply chain which is a small portion of the whole healthcare supply chain, and therefore requires further research covering various other domains of healthcare supply chain. Another limitation of the study is that the sample survey has been taken from only one respondent per company at one point of time which may create biasness in the results. Thus, future research should collect data through multiple members from the organization.Practical implicationsThis study contributes to know the effect of SCM practices on healthcare SCP and provides a practical and useful tool to evaluate the extent of effectiveness of SCP and finally their impact on the healthcare OP. Finally, this study provides conceptual and descriptive literature regarding SCM practices that leads to improvement in healthcare performance.Social implicationsThis study adds to the knowledge on healthcare SCM performance by exploring the relationship between supply chain practices, healthcare SCP and healthcare OP and by developing and testing a research framework thus help in improving patient satisfaction.Originality/valueThis study attempts to show how the potential benefits of supply chain practices can no longer be ignored in healthcare supply chain.

scholarly journals A review of Waste Tyre Rubber as an Alternative Concrete Consituent Material

2018 ◽  
Vol 199 ◽  
pp. 11003 ◽  
Author(s):  
Kudzai Mushunje ◽  
Mike Otieno ◽  
Yunus Ballim
Keyword(s):  
Health And Safety ◽  
Engineering Properties ◽  
Future Research ◽  
Rubber Material ◽  
Safety Risks ◽  
Concrete Production ◽  
Potential Benefits ◽  
Waste Tyre ◽  
Health And Safety Risks ◽  
Published Research

The current global waste tyre generation far exceeds its consumption in terms of recycling and re-use. The traditional recycling and re-use methods like thermal incineration have proven ineffective, costly and in some cases environmentally unsustainable. Particularly, in developing countries where some of the sophisticated techniques required to process tyres to allow them to be utilised are either too costly or have not yet been developed. The situation has resulted in accumulation of large waste tyre stockpiles that pose health and safety risks. To combat the problem, the use of waste tyre rubber in concrete construction has been proposed. Several studies have been conducted to assess the effects of the inclusion of waste tyre rubber in its different forms (fibres, particles), for concrete production and the results are promising. Although there are some apparent demerits to the inclusion of tyre rubber in concrete, the potential benefits seem to overshadow the negatives. This paper reviews published research on the scientific and technical viability of using waste tyre rubber in concrete production. It discusses the production and properties of waste tyre particles. It highlights advances made with regards to the incorporation of tyre rubber material in concrete, focusing on the engineering properties of the tyre rubber modified concrete. In conclusion, recommendations for future research and possible application for the material will be discussed.

MDAPlatform: a Component-based Platform for Constructing and Assessing miRNA-disease association Prediction Methods

2021 ◽  
Vol 16 ◽  
Author(s):  
Yayan Zhang ◽  
Guihua Duan ◽  
Cheng Yan ◽  
Haolun Yi ◽  
Fang-Xiang Wu ◽  
...  
Keyword(s):  
Computational Models ◽  
Critical Role ◽  
Prediction Method ◽  
Disease Association ◽  
Prediction Methods ◽  
Comparison Results ◽  
Disease Associations ◽  
Pros And Cons ◽  
Clinical Drugs ◽  
Validation Experiments

Background: Increasing evidence has indicated that miRNA-disease association prediction plays a critical role in the study of clinical drugs. Researchers have proposed many computational models for miRNA-disease prediction. However, there is no unified platform to compare and analyze the pros and cons or share the code and data of these models. Objective: In this study, we develop an easy-to-use platform (MDAPlatform) to construct and assess miRNA-disease association prediction method. Methods: MDAPlatform integrates the relevant data of miRNA, disease and miRNA-disease associations that are used in previous miRNA-disease association prediction studies. Based on the componentized model, it develops differet components of previous computational methods. Results: Users can conduct cross validation experiments and compare their methods with other methods, and the visualized comparison results are also provided. Conclusion: Based on the componentized model, MDAPlatform provides easy-to-operate interfaces to construct the miRNA-disease association method, which is beneficial to develop new miRNA-disease association prediction methods in the future.

scholarly journals Pathology Study Design, Conduct, and Reporting to Achieve Rigor and Reproducibility in Translational Research Using Animal Models

ILAR Journal ◽  
2018 ◽  
Vol 59 (1) ◽  
pp. 4-12 ◽  
Author(s):  
Jeffrey I Everitt ◽  
Piper M Treuting ◽  
Cheryl Scudamore ◽  
Rani Sellers ◽  
Patricia V Turner ◽  
...  
Keyword(s):  
Animal Models ◽  
Best Practices ◽  
Translational Research ◽  
Safety Assessment ◽  
Animal Studies ◽  
Animal Experiments ◽  
Study Data ◽  
Track Record ◽  
Preclinical Animal Models

AbstractIn translational research, animal models are an important tool to aid in decision-making when taking potential therapies into human clinical trials. Recently, there have been a number of papers that have suggested limited concordance of preclinical animal experiments with subsequent human clinical experience. Assessments of preclinical animal studies have led to concerns about the reproducibility of data and have highlighted the need for an emphasis on rigor and quality in the planning, conduct, analysis, and reporting of such studies. The incorporation of a wider role for the comparative pathologist using pathology best practices in the planning and conduct of animal model-based research is one way to increase the quality and reproducibility of data. The use of optimal design and planning of tissue collection, incorporation of pathology methods into written protocols, conduct of pathology procedures using accepted best practices, and the use of optimal pathology analysis and reporting methods enhance the quality of the data acquired from many types of preclinical animal models and studies. Many of these pathology practices are well established in the discipline of toxicologic pathology and have a proven and useful track record in enhancing the data from animal-based studies used in safety assessment of human therapeutics. Some of this experience can be adopted by the wider community of preclinical investigators to increase the reproducibility of animal study data.

The pros and cons of vertebrate animal models for functional and therapeutic research on inherited retinal dystrophies

2015 ◽  
Vol 48 ◽  
pp. 137-159 ◽  
Author(s):  
Ralph W.N. Slijkerman ◽  
Fei Song ◽  
Galuh D.N. Astuti ◽  
Martijn A. Huynen ◽  
Erwin van Wijk ◽  
...  
Keyword(s):  
Animal Models ◽  
Inherited Retinal Dystrophies ◽  
Retinal Dystrophies ◽  
Pros And Cons ◽  
Therapeutic Research

Presynaptic dysfunction in Parkinson's disease: a focus on LRRK2

2012 ◽  
Vol 40 (5) ◽  
pp. 1111-1116 ◽  
Author(s):  
Elisa Belluzzi ◽  
Elisa Greggio ◽  
Giovanni Piccoli
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Models ◽  
Critical Role ◽  
Dopamine Turnover ◽  
Presynaptic Neuron ◽  
Presynaptic Site ◽  
Promising Target ◽  
Key Factor ◽  
Trafficking Defects

PD (Parkinson's disease) is a common neurodegenerative disease clinically characterized by bradykinesia, rigidity and resting tremor. Recent studies have proposed that synaptic dysfunction, implicated in numerous studies of animal models of PD, might be a key factor in PD. The molecular defects that lead to PD progression might be hidden at the presynaptic neuron: in fact accumulating evidence has shown that the majority of the genes linked to PD play a critical role at the presynaptic site. In the present paper, we focus on the presynaptic function of LRRK2 (leucine-rich repeat kinase 2), a protein that mutated represents the main genetic cause of familial PD described to date. Neurotransmission relies on proper presynaptic vesicle trafficking; defects in this process, variation in dopamine flow and alteration of presynaptic plasticity have been reported in several animal models of LRRK2 mutations. Furthermore, impaired dopamine turnover has been described in presymptomatic LRRK2 PD patients. Thus, given the pathological events occurring at the synapses of PD patients, the presynaptic site may represent a promising target for early diagnostic therapeutic intervention.

scholarly journals The Role of PPARs in Lung Fibrosis

PPAR Research ◽  
2007 ◽  
Vol 2007 ◽  
pp. 1-10 ◽  
Author(s):  
Heather F. Lakatos ◽  
Thomas H. Thatcher ◽  
R. Matthew Kottmann ◽  
Tatiana M. Garcia ◽  
Richard P. Phipps ◽  
...  
Keyword(s):  
Wound Healing ◽  
Animal Models ◽  
Pulmonary Fibrosis ◽  
Lung Fibrosis ◽  
Cardiac Fibrosis ◽  
Rapid Development ◽  
Critical Role ◽  
Normal Lung ◽  
Peroxisome Proliferator ◽  
Ongoing Research

Pulmonary fibrosis is a group of disorders characterized by accumulation of scar tissue in the lung interstitium, resulting in loss of alveolar function, destruction of normal lung architecture, and respiratory distress. Some types of fibrosis respond to corticosteroids, but for many there are no effective treatments. Prognosis varies but can be poor. For example, patients with idiopathic pulmonary fibrosis (IPF) have a median survival of only 2.9 years. Prognosis may be better in patients with some other types of pulmonary fibrosis, and there is variability in survival even among individuals with biopsy-proven IPF. Evidence is accumulating that the peroxisome proliferator-activated receptors (PPARs) play important roles in regulating processes related to fibrogenesis, including cellular differentiation, inflammation, and wound healing. PPARαagonists, including the hypolidipemic fibrate drugs, inhibit the production of collagen by hepatic stellate cells and inhibit liver, kidney, and cardiac fibrosis in animal models. In the mouse model of lung fibrosis induced by bleomycin, a PPARαagonist significantly inhibited the fibrotic response, while PPARαknockout mice developed more serious fibrosis. PPARβ/δappears to play a critical role in regulating the transition from inflammation to wound healing. PPARβ/δagonists inhibit lung fibroblast proliferation and enhance the antifibrotic properties of PPARγagonists. PPARγligands oppose the profibrotic effect of TGF-β, which induces differentiation of fibroblasts to myofibroblasts, a critical effector cell in fibrosis. PPARγligands, including the thiazolidinedione class of antidiabetic drugs, effectively inhibit lung fibrosis in vitro and in animal models. The clinical availability of potent and selective PPARαand PPARγagonists should facilitate rapid development of successful treatment strategies based on current and ongoing research.

scholarly journals The critical role of advanced sustainability assessment tools in enhancing the real-world application of biofuels

2020 ◽  
pp. 67-73
Author(s):  
Meisam Tabatabaei ◽  
Mortaza Aghbashlo
Keyword(s):  
Sustainability Assessment ◽  
Critical Role ◽  
Assessment Tools ◽  
Biofuel Production ◽  
Real World Application ◽  
Production And Consumption ◽  
Energy Accounting ◽  
Pros And Cons ◽  
Sustainability Assessment Tools

Sustainability has become of paramount importance in the biofuel industry. Accordingly, various ‎sustainability assessment schemes such as emergy analysis, techno-economic analysis, life ‎cycle ‎assessment, energy accounting, and exergy analysis and its extensions (exergoeconomic, ‎exergoenvironmental, and ‎exergoeconoenvironmental analyses) are being employed increasingly for decision-‎making on biofuel production and consumption systems. In this opinion paper, after classifying ‎and describing biofuel generations, the developed sustainability assessment tools are critically ‎explained, and their pros and cons are discussed. Overall, among the various sustainability assessment approaches introduced so far, exergy-based methods appear to be ‎the most promising tools for developing ‎sustainable biofuel systems. This can be attributed to the fact that the exergy ‎concept is deeply ‎rooted in the well-defined principles of thermodynamics.‎

scholarly journals A Bottom-Up Review of Image Analysis Methods for Suspicious Region Detection in Mammograms

2021 ◽  
Vol 7 (9) ◽  
pp. 190
Author(s):  
Parita Oza ◽  
Paawan Sharma ◽  
Samir Patel ◽  
Alessandro Bruno
Keyword(s):  
Breast Cancer ◽  
Biomedical Imaging ◽  
Critical Role ◽  
Breast Mri ◽  
Image Features ◽  
Mass Detection ◽  
Bottom Up ◽  
Region Detection ◽  
Suspicious Region ◽  
Pros And Cons

Breast cancer is one of the most common death causes amongst women all over the world. Early detection of breast cancer plays a critical role in increasing the survival rate. Various imaging modalities, such as mammography, breast MRI, ultrasound and thermography, are used to detect breast cancer. Though there is a considerable success with mammography in biomedical imaging, detecting suspicious areas remains a challenge because, due to the manual examination and variations in shape, size, other mass morphological features, mammography accuracy changes with the density of the breast. Furthermore, going through the analysis of many mammograms per day can be a tedious task for radiologists and practitioners. One of the main objectives of biomedical imaging is to provide radiologists and practitioners with tools to help them identify all suspicious regions in a given image. Computer-aided mass detection in mammograms can serve as a second opinion tool to help radiologists avoid running into oversight errors. The scientific community has made much progress in this topic, and several approaches have been proposed along the way. Following a bottom-up narrative, this paper surveys different scientific methodologies and techniques to detect suspicious regions in mammograms spanning from methods based on low-level image features to the most recent novelties in AI-based approaches. Both theoretical and practical grounds are provided across the paper sections to highlight the pros and cons of different methodologies. The paper’s main scope is to let readers embark on a journey through a fully comprehensive description of techniques, strategies and datasets on the topic.

scholarly journals Antinociceptive Effects of Sinomenine Combined With Ligustrazine or Paracetamol in Animal Models of Incisional and Inflammatory Pain

2021 ◽  
Vol 11 ◽  
Author(s):  
Tianle Gao ◽  
Tao Li ◽  
Wei Jiang ◽  
Weiming Fan ◽  
Xiao-Jun Xu ◽  
...  
Keyword(s):  
Animal Models ◽  
Inflammatory Pain ◽  
Extracellular Fluid ◽  
Postoperative Pain Management ◽  
Assay Method ◽  
Pharmacokinetic Studies ◽  
Analgesic Effects ◽  
Pain Models ◽  
Potential Benefits ◽  
Incisional Pain

The management of postoperative and inflammatory pain has been a pressing challenge in clinical settings. Sinomenine (SN) is a morphinan derived alkaloid with remarkable analgesic properties in various kinds of pain models. The aim of the current study is to investigate if SN can enhance the effect of ligustrazine hydrochloride (LGZ) or paracetamol (PCM) in animal models of postoperative and inflammatory pain. And to determine if the combined therapeutic efficacies can be explained by pharmacokinetics changes. Pharmacological studies were performed using a rat model of incisional pain, and a mouse model of carrageenan induced inflammatory pain. Pharmacokinetic studies were performed using a microdialysis sampling and HPLC-MS/MS assay method to quantify SN, LGZ, and PCM levels in blood and extracellular fluid in brain. We found that SN plus LGZ or SN plus PCM produced marked synergistic analgesic effects. However, such synergy was subjected to pain modalities, and differed among pain models. Pharmacological discoveries could be partially linked to pharmacokinetic alterations in SN combinations. Though further evaluation is needed, our findings advocate the potential benefits of SN plus LGZ for postoperative pain management, and SN plus PCM for controlling inflammatory pain.

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