Abstract WP10: Evaluation of a Novel Liquid Embolic Material Using a Rabbit Model: A Hydrophilic Polymer Composite Activated by the Ca2+ in the Blood

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Ichiro Yuki ◽  
Kousaku Ohkawa ◽  
Frank P Hsu ◽  
Jordan C Xu ◽  
Shuichi Suzuki
Keyword(s):  
Organic Solvents ◽  
Hemorrhagic Stroke ◽  
Rabbit Model ◽  
Cerebrovascular Diseases ◽  
Embolic Material ◽  
Complete Occlusion ◽  
Injection Speed ◽  
Liquid Embolic ◽  
Technical Complication

Introduction: Liquid embolic material (LEM) plays an essential role in the treatment of hemorrhagic stroke caused by arteriovenous malformation or dural arteriovenous fistula. However, currently available non-adhesive LEMs has the problem of catheter entrapment, and also known to have a cytotoxic effect due to the organic solvents such as Dimethyl Sulfoxide (DMSO). The New Generation Liquid Embolic Material (NGLEM) is a clear liquid that immediately forms a solid hydrogel cast upon exposure to Ca2+ in the bloodstream, and organic solvents are not required (Figure1). The performance of this new liquid embolic material was evaluated using an in vivo experimental model using rabbit. Methods: Under general anesthesia, a renal artery of New Zealand rabbit (4.5-5.0kg) was catheterized under fluoroscopy using a microcatheter, and NGLEM was injected into the artery. Following factors were assessed; 1) the amount of LEM required for the complete occlusion, 2) injection speed, 3) duration of the injection, 4) radiopacity during the deployment and 5) incidence of catheter entrapment after the injection. Results: Five renal arteries in five rabbits were treated, and all arteries were completely occluded without technical complication. The injected materials immediately formed LEM cast in all vessels followed by the reflux over the microcatheter. All catheters were withdrawn without any sign of catheter entrapment. The NGLEM mixed with both iodine-based (3 animals) and tantalum based (2 animals) contrasts medium showed sufficient radiopacity under fluoroscopy. With the injection speed of 0.02ml/sec, the average volume required was 0.68ml. Average time for the complete occlusion was 237 seconds. No increased thrombogenicity or vasospasm near the treated lesion was observed during the procedure. Conclusions: NGLEM, which is a DMSO free, non-adhesive bio-polymer may be used as an embolic material for the treatment of hemorrhagic stroke caused by cerebrovascular diseases.

Abstract P495: Aqua Embolic System: Evaluating the Performance of a New Liquid Embolic System Using a Swine AVM Model

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Ichiro Yuki ◽  
Kousaku Ohkawa ◽  
Shiri Li ◽  
Earl Steward ◽  
Hsu Frank P.K. ◽  
...  
Keyword(s):  
Renal Artery ◽  
Organic Solvents ◽  
Hemorrhagic Stroke ◽  
Cerebrovascular Diseases ◽  
Left Renal Artery ◽  
Embolic Material ◽  
Injection Speed ◽  
Rete Mirabile ◽  
Brain Avm ◽  
Liquid Embolic

Introduction: Liquid embolic material (LEM) plays an essential role in the treatment of hemorrhagic stroke caused by vascular malformation such as arteriovenous malformations (AVMs). However, currently available non-adhesive LEMs has the problem of catheter entrapment, and also known to have cytotoxicity due to the organic solvents such as Dimethyl Sulfoxide (DMSO). Aqua Embolic System (AES) is a new liquid embolic material, which is mainly composed of multiple polysaccharides. AES, when injected via a microcatheter, immediately forms a solid and elastic hydrogel cast upon exposure to Ca2+ in the bloodstream. The use of organic solvents, e.g., DMSO, is not required. The performance of AES was evaluated using an established AVM model utilizing swine rete-mirabile. Methods: Under general anesthesia, the left ascending pharyngeal artery (APA) of Yorkshire swine (40 kg) was catheterized using a microcatheter (ID:0.013 inches), and AES was slowly injected into the rete-mirabile under fluoroscopy. The following parameters were assessed to evaluate the embolization performance of the AES; 1) the amount of AES required for the complete occlusion of the feeding artery, 2) injection speed, 3) radiopacity during the deployment, and 4) incidence of catheter entrapment after the injection. The same evaluation was performed on the contralateral rete-mirabile and the left renal artery as well. Results: 12 arteries in 4 swine were treated, and all arteries were completely occluded without technical complications. The injected materials immediately formed AES cast in all vessels, followed by the reflux over the tip of the microcatheter. All catheters were withdrawn without any sign of catheter entrapment. The AES mixed with tantalum based contrasts medium showed sufficient radiopacity under fluoroscopy. With the injection speed of 0.02ml/sec, the average volume required was 0.85mL for the APA and 2.9mL for the renal artery. No increased thrombogenicity or vasospasm near the treated lesion was observed during the procedure. Conclusions: AES, which is a DMSO free, non-adhesive polysaccharides-based LEM, may be used as an embolic material for the treatment of hemorrhagic stroke caused by cerebrovascular diseases, such as brain AVM.

scholarly journals In Vivo Assessment of Chitosan/β-Glycerophosphate as a New Liquid Embolic Agent

2011 ◽  
Vol 17 (1) ◽  
pp. 87-92 ◽  
Author(s):  
Y. Wang ◽  
N. Xu ◽  
Q. Luo ◽  
Y. Li ◽  
L. Sun ◽  
...  
Keyword(s):  
Renal Arteries ◽  
Embolic Agent ◽  
Inflammatory Reactions ◽  
Complete Occlusion ◽  
Liquid Embolic ◽  
Feasibility Evaluation ◽  
Liquid Embolic Agent ◽  
In Vivo Assessment

We sought to assess the feasibility of using thermosensitive chitosan/β-glycerophosphate for embolotherapy. The renal arteries in nine rabbits were embolized with chitosan/β-glycerophosphate. The animals were studied angiographically and sacrificed at one week (n = 3), four weeks (n = 3), and eight weeks (n = 3) after embolotherapy. Histology was obtained at these three time points. Delivery of chitosan/β-glycerophosphate was successful in all cases. Complete occlusion was achieved in all cases. No recanalization was observed in the follow-up angiograms. No untoward inflammatory reactions were observed in the target renal arteries and infarcted kidneys during the histological examinations. Our preliminary feasibility evaluation in rabbit renal arteries indicates that C/GP is a satisfactory embolization agent.

Acyl-Enzymes as Thrombolytic Agents in a Rabbit Model of Venous Thrombosis

1982 ◽  
Vol 47 (03) ◽  
pp. 269-274 ◽  
Author(s):  
R A G Smith ◽  
R J Dupe ◽  
P D English ◽  
J Green
Keyword(s):  
Venous Thrombosis ◽  
Active Site ◽  
Fibrinolytic Activity ◽  
Rabbit Model ◽  
Fibrinolytic Agent ◽  
Essential Nature ◽  
Thrombolytic Agents

SummaryA derivative of human lys-plasmin in which the active site has been reversibly acylated (BRL 26920; p-anisoyl human lys-plasmin) has been examined as a fibrinolytic agent in a previously described rabbit model of venous thrombosis and shown to be significantly more active and less fibrinogenolytic than free plasmin. A p-anisoylated derivative of a streptokinase (SK)-activated plasmin preparation was significantly less fibrinogenolytic in vivo than the non-acylated enzyme. Acylation increased the fibrinolytic activity of preparations of SK-plasmin activator complexes. BRL 26921, the active site anisoylated derivative of the primary 2-chain SK-plasminogen complex was the most potent fibrinolytic agent studied. SK-Val442-plasminogen complexes, free or acylated, were biologically inactive in this model and confirm the essential nature of fibrin binding processes for effective thrombolysis in vivo.

scholarly journals Unraveling the molecular pathobiology of vocal fold systemic dehydration using an in vivo rabbit model

PLoS ONE ◽  
2020 ◽  
Vol 15 (7) ◽  
pp. e0236348
Author(s):  
Naila Cannes do Nascimento ◽  
Andrea P. dos Santos ◽  
M. Preeti Sivasankar ◽  
Abigail Cox
Keyword(s):  
Vocal Fold ◽  
Rabbit Model

scholarly journals Evaluation of a bone filler scaffold for local antibiotic delivery to prevent Staphylococcus aureus infection in a contaminated bone defect

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Karen E. Beenken ◽  
Mara J. Campbell ◽  
Aura M. Ramirez ◽  
Karrar Alghazali ◽  
Christopher M. Walker ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bone Defect ◽  
Rabbit Model ◽  
In Vivo Studies ◽  
Bovine Bone ◽  
Bone Filler ◽  
Antibiotic Release ◽  
Local Antibiotic ◽  
Antibiotic Delivery

AbstractWe previously reported the development of an osteogenic bone filler scaffold consisting of degradable polyurethane, hydroxyapatite, and decellularized bovine bone particles. The current study was aimed at evaluating the use of this scaffold as a means of local antibiotic delivery to prevent infection in a bone defect contaminated with Staphylococcus aureus. We evaluated two scaffold formulations with the same component ratios but differing overall porosity and surface area. Studies with vancomycin, daptomycin, and gentamicin confirmed that antibiotic uptake was concentration dependent and that increased porosity correlated with increased uptake and prolonged antibiotic release. We also demonstrate that vancomycin can be passively loaded into either formulation in sufficient concentration to prevent infection in a rabbit model of a contaminated segmental bone defect. Moreover, even in those few cases in which complete eradication was not achieved, the number of viable bacteria in the bone was significantly reduced by treatment and there was no radiographic evidence of osteomyelitis. Radiographs and microcomputed tomography (µCT) analysis from the in vivo studies also suggested that the addition of vancomycin did not have any significant effect on the scaffold itself. These results demonstrate the potential utility of our bone regeneration scaffold for local antibiotic delivery to prevent infection in contaminated bone defects.

scholarly journals β-elemene alleviates airway stenosis via the ILK/Akt pathway modulated by MIR143HG sponging miR-1275

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Guoying Zhang ◽  
Cheng Xue ◽  
Yiming Zeng
Keyword(s):  
Cell Cycle ◽  
Cell Viability ◽  
Cell Model ◽  
Protective Efficacy ◽  
Rabbit Model ◽  
Akt Pathway ◽  
Loss Of Function ◽  
Airway Stenosis

Abstract Background We have previously found that β-elemene could inhibit the viability of airway granulation fibroblasts and prevent airway hyperplastic stenosis. This study aimed to elucidate the underlying mechanism and protective efficacy of β-elemene in vitro and in vivo. Methods Microarray and bioinformatic analysis were used to identify altered pathways related to cell viability in a β-elemene-treated primary cell model and to construct a β-elemene-altered ceRNA network modulating the target pathway. Loss of function and gain of function approaches were performed to examine the role of the ceRNA axis in β-elemene's regulation of the target pathway and cell viability. Additionally, in a β-elemene-treated rabbit model of airway stenosis, endoscopic and histological examinations were used to evaluate its therapeutic efficacy and further verify its mechanism of action. Results The hyperactive ILK/Akt pathway and dysregulated LncRNA-MIR143HG, which acted as a miR-1275 ceRNA to modulate ILK expression, were suppressed in β-elemene-treated airway granulation fibroblasts; β-elemene suppressed the ILK/Akt pathway via the MIR143HG/miR-1275/ILK axis. Additionally, the cell cycle and apoptotic phenotypes of granulation fibroblasts were altered, consistent with ILK/Akt pathway activity. In vivo application of β-elemene attenuated airway granulation hyperplasia and alleviated scar stricture, and histological detections suggested that β-elemene's effects on the MIR143HG/miR-1275/ILK axis and ILK/Akt pathway were in line with in vitro findings. Conclusions MIR143HG and ILK may act as ceRNA to sponge miR-1275. The MIR143HG/miR-1275/ILK axis mediates β-elemene-induced cell cycle arrest and apoptosis of airway granulation fibroblasts by modulating the ILK/Akt pathway, thereby inhibiting airway granulation proliferation and ultimately alleviating airway stenosis.

scholarly journals Development of a photochemical thrombosis investigation system to obtain a rabbit ischemic stroke model

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yoonhee Kim ◽  
Yoon Bum Lee ◽  
Seung Kuk Bae ◽  
Sung Suk Oh ◽  
Jong-ryul Choi
Keyword(s):  
Ischemic Stroke ◽  
Brain Damage ◽  
Rabbit Model ◽  
Specific Area ◽  
Brain Atlas ◽  
Rabbit Brain ◽  
Stroke Model ◽  
Triphenyltetrazolium Chloride ◽  
Induction System

AbstractPhotochemical thrombosis is a method for the induction of ischemic stroke in the cerebral cortex. It can generate localized ischemic infarcts in the desired region; therefore, it has been actively employed in establishing an ischemic stroke animal model and in vivo assays of diagnostic and therapeutic techniques for stroke. To establish a rabbit ischemic stroke model and overcome the shortcoming of previous studies that were difficult to build a standardized photothrombotic rabbit model, we developed a photochemical thrombosis induction system that can produce consistent brain damage on a specific area. To verify the generation of photothrombotic brain damage using the system, longitudinal magnetic resonance imaging, 2,3,5-triphenyltetrazolium chloride staining, and histological staining were applied. These analytical methods have a high correlation for ischemic infarction and are appropriate for analyzing photothrombotic brain damage in the rabbit brain. The results indicated that the photothrombosis induction system has a main advantage of being accurately controlled a targeted region of photothrombosis and can produce cerebral hemisphere lesions on the target region of the rabbit brain. In conjugation with brain atlas, it can induce photochemical ischemic stroke locally in the part of the brain that is responsible for a particular brain function and the system can be used to develop animal models with degraded specific functions. Also, the photochemical thrombosis induction system and a standardized rabbit ischemic stroke model that uses this system have the potential to be used for verifications of biomedical techniques for ischemic stroke at a preclinical stage in parallel with further performance improvements.

scholarly journals Development of Triamcinolone Acetonide-Loaded Microemulsion as a Prospective Ophthalmic Delivery System for Treatment of Uveitis: In Vitro and In Vivo Evaluation

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 444
Author(s):  
Alaa Mahran ◽  
Sayed Ismail ◽  
Ayat A. Allam
Keyword(s):  
Triamcinolone Acetonide ◽  
Delivery System ◽  
Histopathological Examination ◽  
Rabbit Model ◽  
Subconjunctival Injection ◽  
In Vivo Evaluation ◽  
Ternary Phase Diagrams ◽  
Ophthalmic Delivery

Treatment of uveitis (i.e., inflammation of the uvea) is challenging due to lack of convenient ophthalmic dosage forms. This work is aimed to determine the efficiency of triamcinolone acetonide (TA)-loaded microemulsion as an ophthalmic delivery system for the treatment of uveitis. Water titration method was used to construct different pseudo-ternary phase diagrams. Twelve microemulsion formulations were prepared using oleic acid, Cremophor EL, and propylene glycol. Among all tested formulations, Formulation F3, composed of oil: surfactant-co-surfactant (1:1): water (15:35:50% w/w, respectively), was found to be stable and showed acceptable pH, viscosity, conductivity, droplet size (211 ± 1.4 nm), and zeta potential (−25 ± 1.7 mV) and almost complete in vitro drug release within 24 h. The in vivo performance of the optimized formulation was evaluated in experimentally uveitis-induced rabbit model and compared with a commercial TA suspension (i.e., Kenacort®-A) either topically or by subconjunctival injection. Ocular inflammation was evaluated by clinical examination, white blood cell count, protein content measurement, and histopathological examination. The developed TA-loaded microemulsion showed superior therapeutic efficiency in the treatment of uveitis with high patient compliance compared to commercial suspension. Hence, it could be considered as a potential ocular treatment option in controlling of uveitis.

scholarly journals Silane-Coating Strategy for Titanium Functionalization Does Not Impair Osteogenesis In Vivo

Materials ◽  
2021 ◽  
Vol 14 (7) ◽  
pp. 1814
Author(s):  
Plinio Mendes Senna ◽  
Carlos Fernando de Almeida Barros Mourão ◽  
Rafael Coutinho Mello-Machado ◽  
Kayvon Javid ◽  
Pietro Montemezzi ◽  
...  
Keyword(s):  
Bone Formation ◽  
Photoelectron Spectroscopy ◽  
Titanium Surface ◽  
Rabbit Model ◽  
Biologically Active ◽  
Force Microscopy ◽  
Atomic Force ◽  
Silane Coating ◽  
Titanium Screws

Silane-coating strategy has been used to bind biological compounds to the titanium surface, thereby making implant devices biologically active. However, it has not been determined if the presence of the silane coating itself is biocompatible to osseointegration. The aim of the present study was to evaluate if silane-coating affects bone formation on titanium using a rabbit model. For this, titanium screw implants (3.75 by 6 mm) were hydroxylated in a solution of H2SO4/30% H2O2 for 4 h before silane-coating with 3-aminopropyltriethoxysilane (APTES). A parallel set of titanium screws underwent only the hydroxylation process to present similar acid-etched topography as a control. The presence of the silane on the surface was checked by x-ray photoelectron spectroscopy (XPS), with scanning electron microscopy (SEM) and atomic force microscopy (AFM). A total of 40 titanium screws were implanted in the tibia of ten New Zealand rabbits in order to evaluate bone-to-implant contact (BIC) after 3 weeks and 6 weeks of healing. Silane-coated surface presented higher nitrogen content in the XPS analysis, while micro- and nano-topography of the surface remained unaffected. No difference between the groups was observed after 3 and 6 weeks of healing (p > 0.05, independent t-test), although an increase in BIC occurred over time. These results indicate that silanization of a titanium surface with APTES did not impair the bone formation, indicating that this can be a reliable tool to anchor osteogenic molecules on the surface of implant devices.

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