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Paclitaxel Drug-eluting Tracheal Stent Could Reduce Granulation Tissue Formation in a Canine Model

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Chinese Medical Journal 2016年第22期129卷 2708-2713页

作者： Ting Wang Jie Zhang Juan Wang Ying-Hua Pei Xiao-Jian Qiu Yu-Ling Wang Department of Respiratory Beijing Tian Tan Hospital Capital Medical University Beijing 100069 China

Background：Currently available silicone and metallic stents for tracheal stenosis are associated with many problems.Granulation proliferation is one of the main complications.The present study aimed to evaluate the efficacy of paclitaxel drug-eluting tracheal stent in reducing granulation tissue formation in a Canine model,as well as the pharmacokinetic features and safety profiles of the coated drug.Methods：Eight beagles were randomly divided into a control group （bare-metal stent group,n =4） and an experimental group （paclitaxel-eluting stent group,n =4）.The observation period was 5 months.One beagle in both groups was sacrificed at the end of the 1st and 3rd months,respectively.The last two beagles in both groups were sacrificed at the end of 5th month.The proliferation of granulation tissue and changes in tracheal mucosa were compared between the two groups.Blood routine and liver and kidney function were monitored to evaluate the safety of the paclitaxel-eluting stent.The elution method and high-performance liquid chromatography were used to characterize the rate of in vivo release of paclitaxel from the stent.Results：Compared with the control group,the proliferation of granulation tissue in the experimental group was significantly reduced.The drug release of paclitaxel-eluting stent was the fastest in the 1st month after implantation （up to 70.9%）.Then,the release slowed down gradually.By the 54 month,the release reached up to 98.5%.During the observation period,a high concentration of the drug in the trachea （in the stented and adjacent unstented areas） and lung tissue was not noted,and the blood test showed no side effect.Conclusions：The paclitaxel-eluting stent could safely reduce the granulation tissue formation after stent implantation in vivo,suggesting that the paclitaxel-eluting tracheal stent might be considered for potential use in humans in the future.

关键词： Canine Drug-eluting Stent Paclitaxel Tracheal Stenosis

White matter regeneration induced by aligned fibrin nanofiber hydrogel contributes to motor functional recovery in Canine T12 spinal cord injury

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Regenerative Biomaterials 2022年第1期9卷 260-270页

作者： Zheng Cao Weitao Man Yuhui Xiong Yi Guo Shuhui Yang Dongkang Liu He Zhao Yongdong Yang Shenglian Yao Chuzhong Li Lingyun Zhao Xiaodan Sun Hua Guo Guihuai Wang Xiumei Wang State Key Laboratory of New Ceramics and Fine Processing Key Laboratory of Advanced MaterialsSchool of Materials Science and EngineeringTsinghua UniversityBeijing 100084China Department of Neurosurgery Beijing Tsinghua Changgung HospitalSchool of Clinical MedicineTsinghua UniversityBeijing 102218China Center for Biomedical Imaging Research Tsinghua UniversityBeijing 100084China Department of Orthopedics Dongzhimen HospitalBeijing 100007China School of Materials Science and Engineering University of Science and Technology BeijingBeijing 100083China Beijing Neurosurgical Institute Beijing Tiantan HospitalBeijing 100070China

A hierarchically aligned fibrin hydrogel(AFG)that possesses soft stiffness and aligned nanofiber structure has been successfully proven to facilitate neuroregeneration in vitro and in vivo.However,its potential in promoting nerve regeneration in large animal models that is critical for clinical translation has not been sufficiently specified.Here,the effects of AFG on directing neuroregeneration in Canine hemisected T12 spinal cord injuries were explored.Histologically obvious white matter regeneration consisting of a large area of consecutive,compact and aligned nerve fibers is induced by AFG,leading to a significant motor functional restoration.The Canines with AFG implantation start to stand well with their defective legs from 3 to 4 weeks postoperatively and even effortlessly climb the steps from 7 to 8 weeks.Moreover,high-resolution multi-shot diffusion tensor imaging illustrates the spatiotemporal dynamics of nerve regeneration rapidly crossing the lesion within 4 weeks in the AFG group.Our findings indicate that AFG could be a potential therapeutic vehicle for spinal cord injury by inducing rapid white matter regeneration and restoring locomotion,pointing out its promising prospect in clinic practice.

关键词： aligned fibrin hydrogel spinal cord injury white matter regeneration diffusion tensor imaging Canine

Stimulation of in vitro bone formation by Canine prostate cancer

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Journal of Cancer Metastasis and Treatment 2021年第1期7卷 511-523页

作者： Shiyu Yuan Noriko Kantake Daniel E.Hellmann Said M.Elshafae Thomas J.Rosol Department of Biomedical Sciences Heritage College of Osteopathic MedicineOhio UniversityAthensOH 45701USA Molecular and Cellular Biology Program Ohio UniversityAthensOH 45701USA Faculty of Veterinary Medicine Benha UniversityTukhQalyobiya 13736Egypt Ohio Musculoskeletal and Neurological Institute Ohio UniversityAthensOH 45701USA

Aim:Patients with prostate cancer frequently develop osteoblastic bone metastases.Canine models are important because dogs are the only mammal to develop spontaneous prostate cancer with osteoblastic bone metastases similar to men.The mechanism by which prostate cancer induces bone formation is unclear;however,it depends on the complex interaction between prostate cancer cells and bone microenvironment.This study investigated the effects of three Canine prostate cancer cell lines(Ace-1,LuMa,and Probasco)on bone formation and resorption in vitro.Methods:Mouse calvaria were treated with conditioned medium(CM)from cell lines.Calvaria were evaluated by histology,fluorescent calcein uptake at sites of bone mineralization,medium calcium assay,and alkaline phosphatase activity.The expression of bone-related genes was measured using quantitative reverse transcription PCR.Results:A novel calcein uptake assay was developed to measure bone formation and mineralization in vitro.Ace-1 CM induced predominantly bone resorption in calvaria,while Probasco CM induced marked bone formation,mineralization,and healing of calvaria defects.The expression of osteoblast-related genes in calvaria showed that Probasco CM stimulated the maturation and differentiation of osteoblasts and inhibited osteoclastogenesis.Both bone modeling and remodeling were involved in Probasco CM-induced bone formation and mineralization by inhibiting remodeling with zoledronic acid.Inhibition of WNT activity by DKK-1 decreased the osteoblastic activity of Probasco cells.Conclusion:Probasco cells induced bone formation and mineralization in vitro that depended on the WNT signaling pathway.Probasco cells will serve as a valuable model for studying the mechanisms of osteoblastic bone metastasis in prostate cancer.

关键词： Bone Canine dog metastasis osteoblast prostate cancer zoledronic acid DKK-1

Effect of continuous hypothermic machine perfusion transport system（AirdriveTM） on Canine kidney preservation

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Chinese Medical Journal 2014年第6期127卷 1105-1109页

作者： Hu Xiaopeng Xue Wenrui Zhang Qiang Wang Wei Zhang Jiqing Zhang Xiaodong Department of Urology Beijing Chao-Yang Hospital Capital Medical University Beijing 100020 China

Background Organ preservation keeps the quality of the organs under prolonged ischemia. Continuous machineperfusions are gaining an important position in clinical research and practice. The aim of this study was to evaluate theprotective effect of continuous hypothermic machine perfusion transport system （AirdriveTM） on cold ischemic injury ofCanine kidney.

关键词： continuous hypothermic machine perfusion organ preservation organ transplantation Canine kidney common cold preservation

Transcellular transport characteristics of huperzine alone or in combination with ginkgolide B across Caco-2 and Madin-Darby Canine kidney cell monolayer

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Asian Pacific Journal of Tropical Medicine 2014年第11期7卷 889-894页

作者： Wen-Cui Zhao Zhi-Hong Hou Qi Zhang Wei Zheng Pharmacy Department 208th Hospital of PLA. Hospital Office 208th Hospital of PLA. Infirmary 208th Hospital of PLA.

Objective:To study the various processes involved in transcellular transport(TT) of huperzine A alone or in combination with ginkgolide B in Caco-2 and Madin-Darby Canine renal(MDCK)cell monolayer.Methods:The transepithelial passage was assayed in the apical-to-basolateral(AP to BL) direction and opposite direction(BL to AP) in both cell lines.The determination of huperzine A and ginkgolide B were performed by high performance liquid chromatography(HPLC).The passage rates of huperzine A and ginkgolide B were calculated.Bi-directional TT(absorption and secretion) were taken in huperzine A and ginkgolide B in Caco-2 and MDCK cell monolayer.Results:TT absorption and secretion kinetics of huperzine A and ginkgolide B across two cells existed at the same time.The passage rates of huperzine A were increased significantly with adding different concentrations of ginkgolide B.Conclusions:The compound preparations of HA in combination with CB for dementia caused by cerebral ischemic have synergistic effects on the pharmacodynamics,and improve the bioavailability through BBB.

关键词： Caco-2 Huperzine A Ginkgolide B Madin-Darby Canine renal Transcellular Transport

Hyperpolarization activated cation current (If) in cardiac myocytes from pulmonary vein sleeves in the Canine with atrial fibrillation

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Journal of Geriatric Cardiology 2012年第4期9卷 366��-374页

作者： Jia-Yue Li Hong-Juan Wang Bin Xu Xue-Ping Wang Yi-Cheng Fu Mei-Yan Chen De-Xian Zhang Yan Liu Qiao Xue Yang Li Institute of Geriatric Cardiology Chinese PLA General Hospital 28 Fuxing Road Beijing 100853 China

Objective To investigate the characteristics of ectopic automaticity and cation current (If) of cardiac myocytes from pulmonary vein sleeves (PVs) in Canines with atrial fibrillation. Methods The Canines (8–10 years old) were subjected to long-term, rapid atrial pacing (RAP) for 10 weeks, which induced the atrial fibrillation model. Disassociation of PVs of Canines yielded single cardiac myocytes from a Landengorff column. Action potential, If and hyperpolarisation activated cyclic nucleotide-gated (HCN) currents were measured with the patch-clamp technique. Results Compared with the control group, cardiac myocytes from the RAP Canine PVs had spontaneous diastolic depolarization, shorter action potential duration, and larger If densities. In the group of RAP cells, the half maximal activation potential (V1/2) was found to be less negative (��105.5 ±5.2 mV) compared to control cells (��87.3 ±4.9 mV). Current densities of If were increased significantly by β-adrenergic receptor stimulation with isoproterenol and caused an acceleration of current activation. In contrast, If currents in the RAP were reduced by carvedilol, a selective beta-adrenergic receptor. Another important finding is that HCN4-based channels may make a significant contribution to If in PVs cells, but not HCN2. Meanwhile, HCN4 current significantly increases in Canine PVs cardiac myocytes with RAP. Conclusions The spontaneous action potential and larger If currentwere observed in the PVs cardiac myocytes using RAP, whichmay contribute tomore ectopic activity events to trigger and maintain atrial fibrillation.

关键词： Atrial fibrillation Canine Cardiac myocytes Cation current β-receptor

Prospects of diagnostic and prognostic biomarkers of pyometra in Canine

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Asian pacific Journal of Reproduction 2020年第4期9卷 166-173页

作者： Laishram Kipjen Singh Manas Kumar Patra Girish Kumar Mishra Abhishek Chandra Saxena Ujjwal Kumar De Sanjay Kumar Singh Harendra Kumar Krishnaswamy Narayanan Animal Reproduction Division Indian Veterinary Research InstituteIzatnagarU.P.243122India Animal Reproduction Gynaecology and Obstetrics Division ICAR-National Dairy Research InstituteKarnal-132001India Department of Veterinary Gynaecology andObstetrics College of Veterinary Sciences and Animal HusbandryAnjoraDurg(C.G.)India Referral Veterinary Polyclinic ICAR-Indian Veterinary Research InstituteIzatnagarU.P.243122India ICAR-Indian Veterinary Reseach Institute HebbalBangaluru 560024India

Pyometra is one of the most common uterine pathologies of intact bitch at middle to advanced age. In the early stages, the disease shows subtle changes, making diagnosis a challenge. In contrast, at later stages, it manifests as potentially life-threatening systemic inflammatory response syndrome. Ultrasonographic examination of the uterus aids in the diagnosis, although it has limitation in ascertaining the clinical severity of pyometra. Moreover, differentiation of cystic endometrial hyperplasia from pyometra could not be discerned with greater accuracy. Therefore, false negative diagnosis of pyometra patients leads to development of systemic inflammatory response, which delays administration of therapies and results in deaths during early course of treatment. Further, indiscriminate use of broad-spectrum antimicrobials at higher dose in false positive cases considerably contributes to the rising pool of drug resistant pathogens, thereby increasing the risk of case fatality due to sepsis in a long-term. Monitoring the circulating pro-inflammatory cytokines, acute phase proteins, endotoxin, growth factors and inflammatory mediators is the current trend in pyometra research, especially for developing diagnostic and prognostic biomarkers. The present review deals with the prospects of developing diagnostic and prognostic biomarkers in the Canine pyometra.

关键词： Pyometra Systemic inflammatory response Acute-phase proteins Prostaglandin F metabolite Canine

Antifertility effects of Azadirachta indica methanol seed extract on Canine spermatozoa in vitro

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Asian pacific Journal of Reproduction 2020年第3期9卷 135-141页

作者： Chike Fidelis Oguejiofor Ifeanyi Gabriel Eke Kenneth Orji Anya Department of Veterinary Obstetrics and Reproductive Diseases Faculty of Veterinary MedicineUniversity of NigeriaNsukka 410001Nigeria Department of Veterinary Physiology and Pharmacology Faculty of Veterinary MedicineUniversity of NigeriaNsukka 410001Nigeria

Objective:To investigate the effects of Azadirachta(A.)indica methanol seed extract on Canine male fertility in vitro.Methods:The effect of the A.indica methanol seed extract(2.5,5.0,10.0 and 20.0 mg/mL,respectively)on Canine spermatozoa was evaluated in vitro at 1.0,2.5,5.0 and 10.0 min post-treatment.The two controls were comprised of sperm sample in phosphate-buffered saline,and sperm sample in phosphate-buffered saline and 1%dimethyl sulfoxide,respectively.The experiment was repeated(n=3)in duplicates with semen collected from 3 adult Basenjis.The effect of A.indica methanol seed extract treatments on Canine spermatozoal total and progressive motility(phase-contrast microscopy),sperm vitality(eosin-nigrosin vital staining method)and total abnormalities(phase contrast microscopy,eosin-nigrosin staining and Papanicolaou staining methods)were determined.Results:A.indica methanol seed extract treatment caused a concentration and time-dependent decrease in sperm percentage total motility,progressive motility and vitality.The absence of sperm revival post-treatment provided evidence of a permanent or irreversible incapacitation of sperm by A.indica methanol seed extract.Conclusions:The inhibition of sperm motility and significant spermicidal effect observed post-treatment suggest that A.indica methanol seed extract may produce a potent antifertility or contraceptive effect in dogs if applied as an intra-vaginal cream pre-coitus.

关键词： Antifertility Azadirachta indica Canine Spermatozoa Contraceptive

Biotinylated dextran amine anterograde tracing of the Canine corticospinal tract

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Neural Regeneration Research 2012年第11期7卷 805-809页

作者： Xiao Han Guangming Lv Huiqun Wu Dafeng Ji Zhou Sun Yaofu Li Lemin Tang Department of Human Anatomy Institute of Neurobiology Jiangsu Key Laboratory of Neuroregeneration Medical School Nantong University Nantong 226001 Jiangsu Province China Department of Medical Informatics Institute of Digital Medicine Medical School Nantong University Nantong 226001 Jiangsu Province China Department of Medical Image Engineering Medical School Nantong University Nantong 226001 Jiangsu Province China

In this study, biotinylated dextran amine （BDA） was microinjected into the left cortical motor area of the Canine brain. Fluorescence microscopy results showed that a large amount of BDA-labeled pyramidal cells were visible in the left cortical motor area after injection. In the left medulla oblongata, the BDA-labeled corticospinal tract was evenly distributed, with green fluorescence that had a clear boundary with the surrounding tissue. The BDA-positive corticospinal tract entered into the right lateral funiculus of the spinal cord and descended into the posterior part of the right lateral funiculus, close to the posterior horn, from cervical to sacral segments. There was a small amount of green fluorescence in the sacral segment. The distribution of BDA labeling in the Canine central nervous system was consistent with the course of the corticospinal tract. Fluorescence labeling for BDA gradually diminished with time after injection. Our findings indicate that the BDA anterograde tracing technique can be used to visualize the localization and trajectory of the corticospinal tract in the Canine central nervous system.

关键词： biotinylated dextran amine corticospinal tract anterograde tracing fluorescence Canine