scholarly journals Refinement of a mouse cardiovascular model: Development, application and dissemination

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 593
Author(s):  
Kirk A. Taylor ◽  
Michael Emerson

European and UK legislation requires all animal procedures to be conducted with consideration to reduction, refinement and replacement. In this review, 3Rs developments are discussed in the field of platelet biology and thromboembolism. Platelet research requires the use of animal models, and mice are widely used in the field. When working in vitro, conventional light transmission techniques have been scaled down allowing reduction in animal numbers. In vivo, vascular injury models are widely used and work is ongoing to develop ex vivo approaches that use fewer animals. Thromboembolic mortality models, which inflict considerable pain and suffering, have also been used widely. A published and characterised refinement of this mortality model allows real-time monitoring of radiolabelled platelets under general anaesthesia and reduces both the severity level and the numbers of mice used in a typical experiment. This technique is more sensitive than the mortality approach and has opened up new avenues of research, which would not have been feasible by using death as an end-point. To drive uptake of real-time monitoring, a more simplistic approach has been developed involving micro-sampling and cell counting. Thromboembolic mortality models should therefore be considered obsolete due to the emergence of 3Rs models with improved scientific outcomes and that can be implemented relatively easily.

2021 ◽  
Vol 900 ◽  
pp. 115674
Author(s):  
Muthaiah Annalakshmi ◽  
Sakthivel Kumaravel ◽  
T.S.T. Balamurugan ◽  
Shen-Ming Chen ◽  
Ju-Liang He

2015 ◽  
Vol 51 (32) ◽  
pp. 6948-6951 ◽  
Author(s):  
Yanfeng Zhang ◽  
Qian Yin ◽  
Jonathan Yen ◽  
Joanne Li ◽  
Hanze Ying ◽  
...  

Anin vitroandin vivodrug-reporting system is developed for real-time monitoring of drug release via the analysis of the concurrently released near-infrared fluorescence dye.


Sensors ◽  
2020 ◽  
Vol 20 (16) ◽  
pp. 4591 ◽  
Author(s):  
Pablo Blázquez-Carmona ◽  
Manuel Sanchez-Raya ◽  
Juan Mora-Macías ◽  
Juan Antonio Gómez-Galán ◽  
Jaime Domínguez ◽  
...  

For the monitoring of bone regeneration processes, the instrumentation of the fixation is an increasingly common technique to indirectly measure the evolution of bone formation instead of ex vivo measurements or traditional in vivo techniques, such as X-ray or visual review. A versatile instrumented external fixator capable of adapting to multiple bone regeneration processes was designed, as well as a wireless acquisition system for the data collection. The design and implementation of the overall architecture of such a system is described in this work, including the hardware, firmware, and mechanical components. The measurements are conditioned and subsequently sent to a PC via wireless communication to be in vivo displayed and analyzed using a developed real-time monitoring application. Moreover, a model for the in vivo estimation of the bone callus stiffness from collected data was defined. This model was validated in vitro using elastic springs, reporting promising results with respect to previous equipment, with average errors and uncertainties below 6.7% and 14.04%. The devices were also validated in vivo performing a bone lengthening treatment on a sheep metatarsus. The resulting system allowed the in vivo mechanical characterization of the bone callus during experimentation, providing a low-cost, simple, and highly reliable solution.


2019 ◽  
Vol 43 (47) ◽  
pp. 18673-18684 ◽  
Author(s):  
Dan Zhang ◽  
Le Li ◽  
Xiaohui Ji ◽  
Yanhong Gao

Smart GSH-responsive camptothecin delivery systems for treatment of tumors and real-time monitoring in vivo and in vitro were described.


Talanta ◽  
2012 ◽  
Vol 88 ◽  
pp. 631-637 ◽  
Author(s):  
Mira Kim ◽  
Ji Hye Seo ◽  
Won Il Jeon ◽  
Mi-Yeon Kim ◽  
Keunchang Cho ◽  
...  

2015 ◽  
Vol 23 ◽  
pp. S72
Author(s):  
Juliette M.K.M. Delhove ◽  
Dany Perocheau ◽  
Suzanne M.K. Buckley ◽  
Rajvinder Karda ◽  
Simon N. Waddington ◽  
...  

2020 ◽  
Vol 21 (18) ◽  
pp. 6478
Author(s):  
Daniel T. Doty ◽  
Julia Schueler ◽  
Vienna L. Mott ◽  
Cassie M. Bryan ◽  
Nathan F. Moore ◽  
...  

The immune checkpoint blockade represents a revolution in cancer therapy, with the potential to increase survival for many patients for whom current treatments are not effective. However, response rates to current immune checkpoint inhibitors vary widely between patients and different types of cancer, and the mechanisms underlying these varied responses are poorly understood. Insights into the antitumor activities of checkpoint inhibitors are often obtained using syngeneic mouse models, which provide an in vivo preclinical basis for predicting efficacy in human clinical trials. Efforts to establish in vitro syngeneic mouse equivalents, which could increase throughput and permit real-time evaluation of lymphocyte infiltration and tumor killing, have been hampered by difficulties in recapitulating the tumor microenvironment in laboratory systems. Here, we describe a multiplex in vitro system that overcomes many of the deficiencies seen in current static histocultures, which we applied to the evaluation of checkpoint blockade in tumors derived from syngeneic mouse models. Our system enables both precision-controlled perfusion across biopsied tumor fragments and the introduction of checkpoint-inhibited tumor-infiltrating lymphocytes in a single experiment. Through real-time high-resolution confocal imaging and analytics, we demonstrated excellent correlations between in vivo syngeneic mouse and in vitro tumor biopsy responses to checkpoint inhibitors, suggesting the use of this platform for higher throughput evaluation of checkpoint efficacy as a tool for drug development.


2013 ◽  
Vol 110 (08) ◽  
pp. 349-357 ◽  
Author(s):  
Barbara Belfiori ◽  
Eleonora Petito ◽  
Giuseppe Guglielmini ◽  
Lisa Malincarne ◽  
AnnaMaria Mezzasoma ◽  
...  

SummaryAbacavir (ABC) has been associated with ischaemic cardiovascular events in HIV-infected patients, but the pathogenic mechanisms are unknown. Aim of our study was to assess whether ABC induces in vivo platelet activation and ex vivo platelet hyper-reactivity. In a retrospective, case-control study, in vivo platelet activation markers were measured in 69 HIV-infected patients, before starting therapy and after 6–12 months of either ABC (n=35) or tenofovir (TDF) (n=34), and compared with those from 20 untreated HIV-infected patients. A subgroup of patients was restudied after 28–34 months for ex vivo platelet reactivity. In vivo platelet activation markers were assessed by ELISA or flow cytometry, ex vivo platelet reactivity by light transmission aggregometry (LTA) and PFA-100®. The in vitro effects of the ABC metabolite, carbovir triphosphate, on aggregation and intra-platelet cGMP were also studied. sPLA2, sPsel and sGPV increased significantly 6–12 months after the beginning of ABC, but not of TDF or of no treatment. Ex vivo platelet function studies showed enhanced LTA, shorter PFA-100® C/ADP closure time and enhanced platelet expression of P-sel and CD40L in the ABC group. The intake of ABC blunted the increase of intraplatelet cGMP induced by nitric oxide (NO) and acutely enhanced collagen-induced aggregation. Preincubation of control platelets with carbovir triphosphate in vitro enhanced platelet aggregation and blunted NO-induced cGMP elevation. In conclusion, treatment with ABC enhances in vivo platelet activation and induces platelet hyperreactivity by blunting the inhibitory effects of NO on platelets. These effects may lead to an increase of ischaemic cardiovascular events.


Author(s):  
Cedric Jimenez ◽  
Igor Polyakov ◽  
Leigh Kleinert ◽  
André Nelson ◽  
Mark Smith

Abstract Neurothrombectomy devices are commonly evaluated for potential clinical success in porcine models of neurothromboembolism. The majority of preclinical evaluations for these devices are performed in the vasculature of swine or dog utilizing clots created ex vivo. This investigation was conducted to develop a faster, more reliable method for creating clots ex vivo for model development. Neurothrombectomy devices are designed to perform recanalization of arterial occlusions that cause acute ischemic stroke [1]. Recanalization can be achieved via clot disruption, aspiration, or retrieval using one or more mechanical devices. In order to evaluate these devices in vivo, a fast and reliable method for creating and delivering clots to a desired artery, thereby simulating a target site for neurothrombectomy, is essential. Two types of clot analogs (soft or firm) were created using two different methods in order to compare both their mechanical properties and their ability to reliably occlude selected arteries. Utilizing both methods, pre-formed clots were qualitatively compared in vitro to evaluate elasticity, stiffness, and functionality of delivery through a catheter. These evaluations were performed prior to in vivo assessment of the effectiveness of the analogs occlusion of selected arterial vasculature.


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