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Mid-Term Preliminary Results for Safety and Patency of the Occlutech Atrial Flow Regulator in an animal model

Congenital Heart Disease 2022年第3期17卷 269-280页

作者： Kamel Shibbani Daniel McLennan Dunbar Ivy Gareth Morgan Division of Cardiology Department of PediatricsStead Family Children’s HospitalUniversity of Iowa Hospitals and ClinicsIowa CityUSA Division of Cardiology Department of PediatricsMedical College of WisconsinMilwaukeeUSA Division of Cardiology Heart InstituteChildren’s Hospital of ColoradoUniversity of Colorado at DenverAuroraUSA

Objective:The Atrial Flow Regulator(AFR)is a double disc device made of self-expanding Nitinol wire mesh,structured around a central lumen.Once deployed via the transfemoral route,the device stents the atrial septum leaving a preselected fixed diameter atrial communication.We sought to evaluate the mid-term performance of the AFR by implanting the device in 5 healthy porcine hearts to assess safety and patency of the device fenestration over a period of 150 days.Method:Five AFR devices were implanted in 5 female Yucatan adult minipigs.The animals were survived to 150 days with periodic assessments at days+3,+30,+60,+90,+120,and+150.These assessments consisted of transesophageal echocardiography and fluoroscopic evaluation.The animals were sacrificed at day+150.Histological and pathological assessments were carried out to characterize neointimal tissue growth,inflammation,thrombus formation,endothelial coverage,endothelial maturity,and the presence of any luminal thrombus.Result:There were no unscheduled deaths.Patency was maintained in all 5 animals across the 150-day study.There was no statistically significant difference in the lumen diameter over the study duration.Neointimal growth was mild to moderate in all specimens and occurred mostly on the surfaces of the device in direct contact with the atrial septum.There was no evidence of any significant inflammatory response on routine blood work or by imaging or histological assessment.Scanning electron microscope(SEM)examination showed nearly complete surface coverage with endothelial tissue.The animals were in a healthy condition for the duration of the study with no attributable pathology and no adverse effects noted on distant organs in any of the 5 animals.Conclusion:As a continuation of our earlier work,this 150-day midterm animal study provides important safety and feasibility information.Our preliminary results show that the AFR is both safe and effective in maintaining a sustainable atrial level communication for the duration of the study.

关键词： Atrial flow regulator animal model atrial septal defect interventional cardiology device

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Era of the 4D animal model

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animal models and Experimental Medicine 2023年第2期6卷 178-182页

作者： Lihong Zhang Jindan Guo Jiangning Liu NHC Key Laboratory of Human Disease Comparative Medicine Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious DiseasesInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijingChina

Revealing the entire dynamics of pathogenesis is critical for understanding,preventing and treating human disease but is limited by systematic clinical sampling.This drawback can be overcome with animal model studies.Recent advances in phenotyping,omics and bioinformatics technologies promote the development of the 4D animal model to simulate and digitally display the spatiotemporal landscapes of phenotypes and molecular dynamics in human diseases and reveal novel targets for diagnosis and therapy.In this commentary,the origin,supporting technologies,content,function and application,and advantages of 4D animal models over clinical studies and traditional animal models,as well as their limitations,are presented.

关键词： animal model database digitally display human diseases spatiotemporal landscapes

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Experimental models for cancer brain metastasis

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Cancer Pathogenesis and Therapy 2024年第1期2卷 15-23页

作者： Zihao Liu Shanshan Dong Mengjie Liu Yuqiang Liu Zhiming Ye Jianhao Zeng Maojin Yao Guangzhou Institute of Respiratory Disease The First Affiliated Hospital of Guangzhou Medical UniversityChina State Key Laboratory of Respiratory DiseaseGuangzhouGuangdong 510182China Department of Medical Genetics and Cell Biology GMU-GIBH Joint School of Life SciencesGuangzhou Medical UniversityGuangzhouGuangdong 511436China Department of Microbiology Immunologyand Cancer BiologyUniversity of Virginia Health SystemCharlottesvilleVA 22908USA

Brain metastases are a leading cause of cancer-related mortality.However,progress in their treatment has been limited over the past decade,due to an incomplete understanding of the underlying biological mechanisms.Employing accurate in vitro and in vivo models to recapitulate the complexities of brain metastasis offers the most promising approach to unravel the intricate cellular and physiological processes involved.Here,we present a comprehensive review of the currently accessible models for studying brain metastasis.We introduce a diverse array of in vitro and in vivo models,including cultured cells using the Transwell system,organoids,microfluidic models,syngeneic models,xenograft models,and genetically engineered models.We have also provided a concise summary of the merits and limitations inherent to each model while identifying the optimal contexts for their effective utilization.This review serves as a comprehensive resource,aiding researchers in making well-informed decisions regarding model selection that align with specific research questions.

关键词： Brain metastases Blood-brain barrier animal model In vitro model

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Current Situation and Progress of Pig model in Otology Research

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Journal of Biosciences and Medicines 2024年第2期12卷 326-339页

作者： Xiaoping Liu Maomao Ai[] Ying Lin[] Feng Yu Institute of Otolaryngology Head and Neck Surgery Affiliated to Jinan University Guangzhou Red Cross Hospital Affiliated to Jinan University Guangzhou China

Pig models are widely used in otological research. The establishment of common pig and miniature pig animal models has opened up new fields in otological research and is also an ideal large otological animal model. This article introduces the applications, current status, progress, advantages, and issues of using pigs as otologic animal models. It summarizes current research on pigs in the fields of hearing disorders, otitis, vertigo, cochlea, gene editing, and tissue engineering, among other otologic and audiological areas. These models are valuable for translating basic medical science into clinical applications. Based on this, platforms have been established for studying deafness and vertigo, cochlear implantation experiments, stem cell and gene therapy, and tissue engineering. These serve as ideal experimental models for the prevention and treatment of ear diseases, pointing toward new directions. This will bolster the promotion and application of pig models in the fields of tissue engineering and gene editing in the future.

关键词： Pig Miniature Pig animal model

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Effect of lymphotoxin blockage on different stages of Sjogren's syndrome in an animal model

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Rheumatology & Autoimmunity 2022年第2期2卷 76-81页

作者： Alexander Jacob Long Shen Jing He Kelly Nealon Jessy J.Alexander Julian L.Ambrus Jr Department of Medicine SUNY at Buffalo School of MedicineBuffaloNew YorkUSA Department of Rheumatology and Immunology Peking University People's HospitalBeijingChina

Background:Lymphotoxin(LT)is an important mediator in Sjogren's syndrome(SS),both in patients and in animal models.Deletion of the LT alpha gene prevented the development of disease manifestations in the interelukin alpha transgenic mouse(IL14αTG)mouse model of SS.Aims:The current study was designed to evaluate the use of LT inhibitors at different stages of the disease in IL14αTG mice.Materials and Methods:IL14αTG mice were treated with anti‐LTa monoclonal antibody,LTb receptor‐immunoglobulin fusion protein(LTBR‐Ig)or isotype control during different stages of disease and analysis of salivary gland function,immunoglobulins,autoantibodies and histology of internal organs performed.Results and Discussion:The inhibitors were very effective in maintaining salivary gland function and preventing infiltration of the glands with lymphocytes when used in the early stages of the disease.Blocking LT at later stages of the disease did not recover salivary gland function but was still effective in limiting extra glandular manifestations including eye disease and tumor development.Some differences were noted in the effectiveness of anti‐LTαversus LTBR‐Ig in limiting particular disease manifestations.Conclusion:LT inhibitors deserve further investigation in the management of SS at whatever stage is identified.

关键词： animal model lymphotoxin Sjogren's syndrome

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Guinea pigs as an animal model for sciatic nerve injury

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Neural Regeneration Research 2017年第3期12卷 452-457页

作者： Malik Abu Rafee Amarpal Prakash Kinjavdekar Hari Prasad Aithal Sajad Ahmad Wani Irfan Ahmad Bhat Division of Surgery Indian Veterinary Research InstituteIzatnagarBareillyUPIndia Division of Veterinary Biotechnology Indian Veterinary Research InstituteIzatnagarBareillyUPIndia Division of Veterinary Physiology Indian Veterinary Research InstituteIzatnagarBareillyUPIndia

The overwhelming use of rat models in nerve regeneration studies is likely to induce skewness in treatment outcomes.To address the problem,this study was conducted in 8 adult guinea pigs of either sex to investigate the suitability of guinea pig as an alternative model for nerve regeneration studies.A crush injury was inflicted to the sciatic nerve of the left limb,which led to significant decrease in the pain perception and neurorecovery up to the 4th weak.Lengthening of foot print and shortening of toe spread were observed in the paw after nerve injury.A 3.49 ± 0.35 fold increase in expression of neuropilin 1（NRP1） gene and 2.09 ± 0.51 fold increase in neuropilin 2（NRP2） gene were recorded 1 week after nerve injury as compared to the normal nerve.Ratios of gastrocnemius muscle weight and volume of the experimental limb to control limb showed more than 50% decrease on the 30 th day.Histopathologically,vacuolated appearance of the nerve was observed with presence of degenerated myelin debris in digestion chambers.Gastrocnemius muscle also showed degenerative changes.Scanning electron microscopy revealed loose and rough arrangement of connective tissue fibrils and presence of large spherical globules in crushed sciatic nerve.The findings suggest that guinea pigs could be used as an alternative animal model for nerve regeneration studies and might be preferred over rats due to their cooperative nature while recording different parameters.

关键词： nerve regeneration Guinea pigs animal model sciatic nerve injury foot print length neuropilin histopathology neural regeneration

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Tree shrew (Tupaia belangeri)as a novel laboratory disease animal model

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Zoological Research 2017年第3期38卷 127-137页

作者： Ji Xiao Rong Liu Ce-Shi Chen Medical Faculty of Kunming University of Science and Technology Kunming Yunnan 650500 China Key Laboratory of animal models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province Kunming Institute of Zoology Chinese Academy of Sciences Kunming Yunnan 650223 China

The tree shrew （Tupaia belangeri） is a promising laboratory animal that possesses a closer genetic relationship to primates than to rodents. In addition, advantages such as small size, easy breeding, and rapid reproduction make the tree shrew an ideal subject for the study of human disease. Numerous tree shrew disease models have been generated in biological and medical studies in recent years. Here we summarize current tree shrew disease models, including models of infectious diseases, cancers, depressive disorders, drug addiction, myopia, metabolic diseases, and immune-related diseases. With the success of tree shrew transgenic technology, this species will be increasingly used in biological and medical studies in the future.

关键词： Tree shrew （Tupaia belangeri） animal model Transgenic Disease

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Functional magnetic resonance imaging in an animal model of pancreatic cancer

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World Journal of Gastroenterology 2010年第26期16卷 3292-3298页

作者： Robert J Lewandowski Aaron C Eifler David J Bentrem Johnathan C Chung Gayle E Woloschak Robert Ryu Riad Salem Andrew C Larson Reed A Omary Department of Radiology Northwestern University Feinberg School of Medicine Chicago IL 60611 United States Department of Surgical Oncology Northwestern University Feinberg School of Medicine Chicago IL 60611 United States Department of Radiation Oncology Northwestern University Feinberg School of Medicine Chicago IL 60611 United States

AIM: To test the hypotheses that diffusion weighed (DW)and transcatheter intraarterial perfusion (TRIP)magnetic resonance imaging (MRI) can each be used to assess regional differences in tumor function in an animal pancreatic cancer model.METHODS: VX2 tumors were implanted in pancreata of 6 rabbits. MRI and digital subtraction angiography (DSA) were performed 3 wk following implantation. With a 2-French catheter secured in the rabbit's gastroduodenal artery, each rabbit was transferred to an adjacent 1.5T MRI scanner. DWand TRIP-MRI were performed to determine if necrotic tumor core could be differentiated from viable tumor periphery. For each, we compared mean differences between tumor core/ periphery using a 2-tailed paired t-test (α = 0.05). Imaging was correlated with histopathology. RESULTS: Tumors were successfully grown in all rabbits, confirmed by necropsy. On DW-MRI, mean apparent diffusion coeffi cient (ADC) value was higher in necrotic tumor core (2.1 ± 0.3 mm2/s) than in viable tumor periphery (1.4 ± 0.5 mm2/s) (P animal pancreatic cancer model using ADC (DW-MRI) and perfusion (TRIP-MRI) values.

关键词： animal model Functional magnetic resonance imaging Pancreatic cancer

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Lower respiratory tract samples are reliable for severe acute respiratory syndrome coronavirus 2 nucleic acid diagnosis and animal model study

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Zoological Research 2021年第2期42卷 161-169页

作者： Ren-Rong Tian Cui-Xian Yang Mi Zhang Xiao-Li Feng Rong-Hua Luo Zi-Lei Duan Jian-Jian Li Jia-Fa Liu Dan-Dan Yu Ling Xu Hong-Yi Zheng Ming-Hua Li Hong-Li Fan Jia-Li Wang Xing-Qi Dong Yong-Tang Zheng Key Laboratory of animal models and Human Disease Mechanisms of the Chinese Academy of Sciences KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common DiseasesKunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China Center for Biosafety Mega-Science Kunming Institute of ZoologyChinese Academy of SciencesKunmingYunnan 650223China Yunnan Infectious Diseases Hospital KunmingYunnan 650301China

Severe acute respiratory syndrome coronavirus 2(SARS-Co V-2) and coronavirus disease 2019(COVID-19) continue to impact countries worldwide.At present, inadequate diagnosis and unreliable evaluation systems hinder the implementation and development of effective prevention and treatment strategies. Here, we conducted a horizontal and longitudinal study comparing the detection rates of SARS-Co V-2 nucleic acid in different types of samples collected from COVID-19 patients and SARS-Co V-2-infected monkeys. We also detected anti-SARS-Co V-2 antibodies in the above clinical and animal model samples to identify a reliable approach for the accurate diagnosis of SARS-Co V-2 infection. Results showed that, regardless of clinical symptoms, the highest detection levels of viral nucleic acid were found in sputum and tracheal brush samples, resulting in a high and stable diagnosis rate. Anti-SARS-Co V-2 immunoglobulin M(Ig M) and G(Ig G) antibodies were not detected in6.90% of COVID-19 patients. Furthermore,integration of nucleic acid detection results from the various sample types did not improve the diagnosis rate. Moreover, dynamic changes in SARS-Co V-2 viral load were more obvious in sputum and tracheal brushes than in nasal and throat swabs. Thus,SARS-Co V-2 nucleic acid detection in sputum and tracheal brushes was the least affected by infection route, disease progression, and individual differences. Therefore, SARS-Co V-2 nucleic acid detection using lower respiratory tract samples alone is reliable for COVID-19 diagnosis and study.

关键词： COVID-19 SARS-CoV-2 Diagnosis animal model

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Dorsal root ganglion compression as an animal model of sciatica and low back pain

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Neuroscience Bulletin 2012年第5期28卷 618-630页

作者： Xiao-Yu Lin Jing Yang Hui-Ming Li San-Jue Hu Jun-Ling Xing Class 2008 School of Stomatology Department of Cardiology The 323 Military Hospital Xi'an 710054 China Institute of Neuroscience Fourth Military Medical University Xi'an 710032 China

As sciatica and low back pain are among the most common medical complaints, many studies have duplicated these conditions in animals. Chronic compression of the dorsal root ganglion （CCD） is one of these models. The surgery is simple： after exposing the L4/L5 intervertebral foramina, stainless steel rods are implanted unilaterally, one rod for each vertebra, to chronically compress the lumbar dorsal root ganglion （DRG）. Then, CCD can be used to simulate the clinical conditions caused by stenosis, such as a laterally herniated disc or foraminal stenosis. As the intraforaminal implantation of a rod results in neuronal somal hyperexcitability and spontaneous action potentials associated with hyperalgesia, spontaneous pain, and mechanical allodynia, CCD provides an animal model that mimics radicular pain in humans. This review concerns the mechanisms of neuronal hyperexcitability, focusing on various patterns of spontaneous discharge including one possible pain signal for mechanical allodynia - evoked bursting. Also, new data regarding its significant property of maintaining peripheral input are also discussed. Investigations using this animal model will enhance our un-derstanding of the neural mechanisms for low back pain and sciatica. Furthermore, the peripheral location of the DRG fa-cilitates its use as a locus for controlling pain with minimal central effects, in the hope of ultimately uncovering analgesics that block neuropathic pain without influencing physiological pain.

关键词： animal model sciatica low back pain dorsal root ganglion excitability cytokine analgesia

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