Tumor hepático experimental (VX-2 em coelho: implantação do modelo no Brasil Experimental liver tumor (VX-2 in rabbits: implantation of the model in Brazil

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Rogério Saad Hossne

2002-08-01

Full Text Available Os estudos para a investigação de novas modalidades terapêuticas em biologia tumoral, deveriam passar por estudos experimentais prévios. Neste sentido dispõem-se hoje de uma grande variedade de modelos tumorais experimentais; em determinadas investigações faz-se necessária a adequação do modelo tumoral às necessidades biológicas, patológicas e experimentais dos estudos. Desta forma, em nosso serviço, buscávamos um modelo tumoral hepático para estudos experimentais que se adequasse às seguintes características: fácil manipulação, crescimento controlável, evolução e agressividade semelhantes aos seres humanos. Os dados da literatura nos levaram a busca do tumor hepático VX-2, em coelhos. Neste artigo discutimos as vantagens da utilização deste modelo experimental e a sua introdução em nosso país.Studies for investigation of new therapeutic modalities in tumoral biology should be based on previous experimental studies. Then, there are a great variety of tumoral experimental models today. Some investigations have been done necessary an adaptation of the tumoral model to the needing of the studies biological and pathological. So, in our laboratory, we looked for a tumoral hepatic model for experimental studies with the following characteristics: easy manipulation, control of growing, evolution and aggressiveness like to humans. Data of the literature took us the search of the hepatic tumor VX-2, in rabbits. In this article we discussed the advantages of use this experimental model and its introduction in our country. Experimental hepatic tumor (VX-2 in rabbit. Implantation of the model in Brazil.

Necrosis targeted radiotherapy with iodine-131-labeled hypericin to improve anticancer efficacy of vascular disrupting treatment in rabbit VX2 tumor models.

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Shao, Haibo; Zhang, Jian; Sun, Ziping; Chen, Feng; Dai, Xu; Li, Yaming; Ni, Yicheng; Xu, Ke

2015-06-10

A viable rim of tumor cells surrounding central necrosis always exists and leads to tumor recurrence after vascular disrupting treatment (VDT). A novel necrosis targeted radiotherapy (NTRT) using iodine-131-labeled hypericin (131I-Hyp) was specifically designed to treat viable tumor rim and improve tumor control after VDT in rabbit models of multifocal VX2 tumors. NTRT was administered 24 hours after VDT. Tumor growth was significantly slowed down by NTRT with a smaller tumor volume and a prolonged tumor doubling time (14.4 vs. 5.7 days), as followed by in vivo magnetic resonance imaging over 12 days. The viable tumor rims were well inhibited in NTRT group compared with single VDT control group, as showed on tumor cross sections at day 12 (1 vs. 3.7 in area). High targetability of 131I-Hyp to tumor necrosis was demonstrated by in vivo SPECT as high uptake in tumor regions lasting over 9 days with 4.26 to 98 times higher radioactivity for necrosis versus the viable tumor and other organs by gamma counting, and with ratios of 7.7-11.7 and 10.5-13.7 for necrosis over peri-tumor tissue by autoradiography and fluorescence microscopy, respectively. In conclusion, NTRT improved the anticancer efficacy of VDT in rabbits with VX2 tumors.

FDG-PET for Evaluating the Antitumor Effect of Intraarterial 3-Bromopyruvate Administration in a Rabbit VX2 Liver Tumor Model

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Park, Hee Sun; Chung, Jin Wook; Jae, Hwan Jun

2007-01-01

We wanted to investigate the feasibility of using FDG-PET for evaluating the antitumor effect of intraarterial administration of a hexokinase II inhibitor, 3-bromopyruvate (3-BrPA), in a rabbit VX2 liver tumor model. VX2 carcinoma was grown in the livers of ten rabbits. Two weeks later, liver CT was performed to confirm appropriate tumor growth for the experiment. After tumor volume-matched grouping of the rabbits, transcatheter intraarterial administration of 3-BrPA was performed (1 mM and 5 mM in five animals each, respectively). FDG-PET scan was performed the day before, immediately after and a week after 3-BrPA administration. FDG uptake was semiquantified by measuring the standardized uptake value (SUV). A week after treatment, the experimental animals were sacrificed and the necrosis rates of the tumors were calculated based on the histopathology. The SUV of the VX2 tumors before treatment (3.87±1.51 [mean SD]) was significantly higher than that of nontumorous liver parenchyma (1.72±0.34) (p < 0.0001, Mann-Whitney U test). The SUV was significantly decreased immediately after 3-BrPA administration (2.05±1.21) (p = 0.002, Wilcoxon signed rank test). On the one-week follow up PET scan, the FDG uptake remained significantly lower (SUV 1.41±0.73) than that before treatment (p 0.002), although three out of ten animals showed a slightly increasing tendency for the FDG uptake. The tumor necrosis rate ranged from 50.00% to 99.90% (85.48%±15.87). There was no significant correlation between the SUV or the SUV decrease rate and the tumor necrosis rate in that range. Even though FDG-PET cannot exactly reflect the tumor necrosis rate, FDG-PET is a useful modality for the early assessment of the antitumor effect of intraarterial administration of 3-BrPA in VX2 liver tumor

FDG-PET for Evaluating the Antitumor Effect of Intraarterial 3-Bromopyruvate Administration in a Rabbit VX2 Liver Tumor Model

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Park, Hee Sun; Chung, Jin Wook; Jae, Hwan Jun [Seoul National University College of Medicine, Seoul (Korea, Republic of)] (and others)

2007-06-15

We wanted to investigate the feasibility of using FDG-PET for evaluating the antitumor effect of intraarterial administration of a hexokinase II inhibitor, 3-bromopyruvate (3-BrPA), in a rabbit VX2 liver tumor model. VX2 carcinoma was grown in the livers of ten rabbits. Two weeks later, liver CT was performed to confirm appropriate tumor growth for the experiment. After tumor volume-matched grouping of the rabbits, transcatheter intraarterial administration of 3-BrPA was performed (1 mM and 5 mM in five animals each, respectively). FDG-PET scan was performed the day before, immediately after and a week after 3-BrPA administration. FDG uptake was semiquantified by measuring the standardized uptake value (SUV). A week after treatment, the experimental animals were sacrificed and the necrosis rates of the tumors were calculated based on the histopathology. The SUV of the VX2 tumors before treatment (3.87{+-}1.51 [mean SD]) was significantly higher than that of nontumorous liver parenchyma (1.72{+-}0.34) (p < 0.0001, Mann-Whitney U test). The SUV was significantly decreased immediately after 3-BrPA administration (2.05{+-}1.21) (p = 0.002, Wilcoxon signed rank test). On the one-week follow up PET scan, the FDG uptake remained significantly lower (SUV 1.41{+-}0.73) than that before treatment (p 0.002), although three out of ten animals showed a slightly increasing tendency for the FDG uptake. The tumor necrosis rate ranged from 50.00% to 99.90% (85.48%{+-}15.87). There was no significant correlation between the SUV or the SUV decrease rate and the tumor necrosis rate in that range. Even though FDG-PET cannot exactly reflect the tumor necrosis rate, FDG-PET is a useful modality for the early assessment of the antitumor effect of intraarterial administration of 3-BrPA in VX2 liver tumor.

FDG-PET for Evaluating the Antitumor Effect of Intraarterial 3-Bromopyruvate Administration in a Rabbit VX2 Liver Tumor Model

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Park, Hee Sun; Jae, Hwan Jun; Kim, Young Il; Son, Kyu Ri; Lee, Min Jong; Park, Jae Hyung; Kang, Won Jun; Yoon, Jung Hwan; Chung, Hesson; Lee, Kichang

2007-01-01

Objective We wanted to investigate the feasibility of using FDG-PET for evaluating the antitumor effect of intraarterial administration of a hexokinase II inhibitor, 3-bromopyruvate (3-BrPA), in a rabbit VX2 liver tumor model. Materials and Methods VX2 carcinoma was grown in the livers of ten rabbits. Two weeks later, liver CT was performed to confirm appropriate tumor growth for the experiment. After tumor volume-matched grouping of the rabbits, transcatheter intraarterial administration of 3-BrPA was performed (1 mM and 5 mM in five animals each, respectively). FDG-PET scan was performed the day before, immediately after and a week after 3-BrPA administration. FDG uptake was semiquantified by measuring the standardized uptake value (SUV). A week after treatment, the experimental animals were sacrificed and the necrosis rates of the tumors were calculated based on the histopathology. Results The SUV of the VX2 tumors before treatment (3.87 ±1.51 [mean ±SD]) was significantly higher than that of nontumorous liver parenchyma (1.72 ±0.34) (p < 0.0001, Mann-Whitney U test). The SUV was significantly decreased immediately after 3-BrPA administration (2.05 ±1.21) (p = 0.002, Wilcoxon signed rank test). On the one-week follow up PET scan, the FDG uptake remained significantly lower (SUV 1.41 ±0.73) than that before treatment (p = 0.002), although three out of ten animals showed a slightly increasing tendency for the FDG uptake. The tumor necrosis rate ranged from 50.00% to 99.90% (85.48% ±15.87). There was no significant correlation between the SUV or the SUV decrease rate and the tumor necrosis rate in that range. Conclusion Even though FDG-PET cannot exactly reflect the tumor necrosis rate, FDG-PET is a useful modality for the early assessment of the antitumor effect of intraarterial administration of 3-BrPA in VX2 liver tumor. PMID:17554189

Hepatic VX2 tumor after portal vein occlusion in rabbits: evaluation with DSA

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Qi Yueyong; Zou Liguang; Dai Shuhua; Zhang Qichuan; Chen Lin; Huang Xiaobing; Huan Guangqiang

2006-01-01

Objective: To study the value of DSA for hepatic vascular anatomy, and to evaluate the efficacy of portal vein occlusion in rabbits with hepatic VX2 tumor. Methods: Twenty New Zealand white rabbits were randomly divided into two groups with 10 in each group, including test group A and positive control group B of ham operation. For the test group A, portal branch ligation (PBL) was performed for the left external branch after 3 weeks of the tumor implantation to the left external lobe. Two weeks later, the DSA of hepatic artery and portal vein were performed in all of the rabbits. Results: The total displaying effectiveness of the branches of hepatic artery by DSA was better than that by vascular perfusion. There was hypovascular blood supply to hepatic artery implantation of the tumor in the test group A, comparing with that of the group B. Conclusion: DSA can clearly display special details of the hepatic vascular anatomy in rabbits, and play an important role in post-procedural evaluation of the portal vein occlusion in rabbits. (authors)

Empirical study of 99Tcm-HYNIC-A(D) A(D) APRPG in rabbit model of inflammation and VX2 tumor xenografted

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Liu Ciyi; Song Shaoli; Xie Wenhui; Cai Xiaojia; Zhang Lihua; Huang Gang

2011-01-01

Objective: To investigate the uptake of 99 Tc m -hydrazinonicotinamide-D-alanine- D-alanine-alanine-proline-arginine-proline-glycine (HYNIC-A(D) A(D) APRPG) in rabbit models of inflammation and VX2 tumor xenografted, so as to evaluate its use as a new tracer for tumor angiogenesis. Methods: Ten rabbit models of xenoplanted VX2 tumor and inflammation were randomly divided into two groups which were injected with different injected tracers, 99 Tc m -HYNIC-A(D) A (D)APRPG 99 Tc m -RGD, followed by serial Gamma images at various time points. The first group underwent 18 F-FDG PET ahead of 99 Tc m -HYNICA(D)A (D) APRPG SPECT. Analysis of variance and t-test were performed with SPSS 10.0. Results: 99 Tc m -HYNIC-A(D) A (D)APRPG scan showed negative uptake at inflammation focus but positive uptake at tumor. Pathological examination confirmed high 99 Tc m -HYNIC-A(D)A(D) APRPG accumulation in tumor cells, with the highest tumor/inflammation ratio (3.25±0.171) at 2 h post-injection, which was significantly higher than that of 99 Tc m -RGD (2.37±0.076) (F = 15.63, P 99 Tc m -HYNIC-A(D)A(D)APRPG, 99 Tc m -RGD, 18 F-FDG were significantly different at 0.5, 1, 2, 3, 6 h (F=13.83∼26.41; t =23.84, 12.75; all P 99 Tc m -HYNIC-A (D) A (D)APRPG can be used as a potential tracer for tumor angiogenesis. (authors)

Hepatic parenchymal changes following transcatheter embolization and chemoembolization in a rabbit tumor model.

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Yong Wang

Full Text Available OBJECTIVE: To compare the effects of transcatheter arterial chemoembolization (TACE with transcatheter arterial embolization (TAE on liver function, hepatic damage, and hepatic fibrogenesis in a rabbit tumor model. MATERIALS AND METHODS: Thirty-nine New Zealand white rabbits implanted with VX2 tumors in the left liver lobes were randomly divided into three groups: TAE, TACE, and control group. In the TAE group (n = 15, polyvinyl alcohol particles (PVAs were used for left hepatic artery embolization. In the TACE group (n = 15, the tumors were treated with left hepatic arterial infusions of a suspension of 10-hydroxycamptothecin and lipiodol, followed by embolization with PVAs. In the control group (n = 9, the animals received sham treatment with distilled water. Serum and liver samples were collected at 6 hours, 3 days and 7 days after treatment. Liver damage was measured using a liver function test and histological analyses. Liver fibrogenesis and hepatic stellate cell (HSC activation were evaluated using Sirius Red and anti-alpha-smooth muscle actin (α-SMA immunohistochemical stains. RESULTS: TACE caused liver injury with greater increases in serum alanine aminotransferase and aspartate aminotransferase levels on day 3 (P<0.05. Histological analyses revealed increased hepatic necrosis in adjacent non-tumorous liver tissue from day 3 compared to the TAE group (Suzuki score of 2.33±1.29 versus 1.13±1.18, P = 0.001. HSC activation and proliferation were significantly increased in the TACE group compared to the control group at 3 and 7 days after treatment (0.074±0.014 vs. 0.010±0.006, and 0.088±0.023 vs. 0.017±0.009, P<0.05. Sirius Red staining demonstrated a statistically significant increase in collagen deposition in the livers in the TACE group 7 days after embolization compared to the control group (0.118±0.012 vs. 0.060±0.017, P = 0.05. CONCLUSION: The results of this animal study revealed that TACE induced

Effect of interventional treatment with p53 on the invasion and metastasis of VX2 liver tumor in experimental rabbits

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Li Caixia; Feng Yan; Gu Tao; Li Chunmei

2010-01-01

Objective: To investigate the effect of interventional treatment with p53 on the invasion and metastasis of VX2 liver tumor in experimental rabbits. Methods: VX2 carcinoma cells were surgically implanted into the left hepatic lobe in 48 New Zealand white rabbits, and the rabbit hepatic carcinoma models were thus established. The rabbits were randomly divided into 4 groups with 12 rabbits in each group. After hepatic arterial catheterization was completed physiological saline (control group), Lipiodol (Group A), Ad-p53 (Group B) and Lipiodol+Ad-p53 (Group C) were respectively infused into the rabbits of four groups via common hepatic artery. One week after the procedure the rabbits were sacrificed and the livers were removed for the determination of matrix metalloprotein-2 (MMP-2), proliferating cell nuclear antigen (PCNA) and vascular endothelial growth factor (VEGF) of the tumor with immunohistochemistry technique. Results: The tumor growth in study groups (group A, B and C) was markedly suppressed, which was significantly different in comparison with that in control group (P 0.05). The positive rates of MMP-2, PCNA and VEGF in group B and C were significantly lower than those in control group (P < 0.05). The positive rates of MMP-2, PCNA and VEGF of the rabbits with metastasis were markedly higher than those without metastasis(P < 0.05). MMP-2 bore a certain relationship with VEGF and PCNA (P < 0.05). Conclusion: The increase of the positive rates of MMP-2, PCNA and VEGF indicates that the tumor possesses higher possibility for developing metastasis, proliferation and vascular formation. The interventional treatment with Adp53 or Lipiodol+Ad-p53 can inhibit the growth, metastasis and vascular formation of VX2 liver tumor in experimental rabbits. (J Intervent Radiol, 2010, 19 : 800-804) (authors)

Measurement of pO2 in a Pre-clinical Model of Rabbit Tumor Using OxyChip, a Paramagnetic Oxygen Sensor.

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Hou, H; Khan, N; Kuppusamy, P

2017-01-01

The objective of this work was to establish a novel and robust technology, based on electron paramagnetic resonance (EPR) oximetry, as a practical tool for measurement of tumor oxygen. Previously, we have reported on the development of oxygen-sensing paramagnetic crystals (LiNc-BuO) encapsulated in a biocompatible polymer, called OxyChip. In this report we present our recent data on the use of OxyChip for pO 2 measurements in the tumor of a pre-clinical, large-animal rabbit model. The results establish that OxyChip is capable of noninvasive and repeated measurement of pO 2 in a large animal model.

Study of CT-guided iodine-125 implantation in the treatment of rabbit VX2 tumor

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He Kewu; Gao Bin; Li Jiajia

2008-01-01

Objective: To evaluate the effect of CT-guided iodine-125 seed( 125 I) implantation to rabbit model VX2 tumor cell apoptosis. Methods: VX2 tumor cells were implanted into muscle of 40 rabbits legs, 3 weeks later, as the diameter of tumor reached 2 cm available for test. Randomly selected the sampling tumor on one leg of rabbit as for the test team and tumor on the contralateral leg as for control team. Under CT guidance, 125 I seeds were implanted into 20 tumor lesions of the test team, and hollow seeds were implanted into 20 tumor lesions of the control team. Instantly, 72 h, 1, 2, 3 w after operation, percutaneous tumor tissue sampling was done 0.5-1.0 cm and 1.0-1.5 cm away from seed implanted site under CT guidance; and apoptosis was investigated by FCM. Results: Instantly, 72 h, 1, 2, 3 w after treatment with iodine-125 ( 125 I) implantation, the tissue sampling away from seed 0.5-1.0 cm showed the apoptosis rates of control team and test team were respectively as follows: (5.43±0.67)% and (5.48±0.66)%, (P>0.05), (5.45±0.58)% and (11.60±0.87)%, (P O.05)of the control team and test team. Conclusions: 125 I seeds implantation can induce tumor cell apoptosis, beginning at 72 h and reached peak at 2 w and kept the high level here afterword. The apoptosis rate descended rapidly along with the increase of distance away from the 125 I seedling. (authors)

LP-THAE induced tumor cell apoptosis of rabbit VX2 liver carcinoma

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Chen Shengli; Quan Yi; Huang Zicheng; Chen Guodong; Zhu Dongliang

2007-01-01

Objective: To research tumor cell apoptosis induced by Lp-THAE of rabbit VX2 liver implanted tumor. Methods: 27 New Zealand white rabbits implanted with VX2 tumor at left middle lobe of the liver divided into three groups: Group A(n= 9) Lp-THAE: treated through transhepatic artery catheterization; Group B(n=9) THAI and Group C(n=9) as control. The rabbits were executed at second to fifth day after treatment. HE dye microscopy was taken for counting the typical apoptosis cells and calculating apoptosis index (ApI). FITC-AnnexinV/PI assay was used for measuring apoptosis by flow cytometry. Results: The ApI of tumor central area and marginal area were (17.769±2.417)%, (4.129±1.172)%, P<0.01. The percentages of tumor cell apoptosis and tumor cell necrosis were (16.483±1.404)%, (9.478±0.964)%, P<0.01 and (43.559±5.053)%, (33.460±1.840)%, P=0.093. The total percentages of tumor cell apoptosis and necrosis were (60.042±13.979)%, (42.938±8.979)%, P< 0.01, at tumor center and marginal area in THAE group respectively. The ApI, percentages of tumor cell apoptosis and necrosis in THAE group were significantly higher than those of THAI group (P<0.01). The percentages of tumor cell apoptosis at tumor center area in THAE group were significantly higher than those of tumor marginal area(P<0.01). Conclusion: Induced tumor cell apoptosis and necrosis are two mechanisms of action for Lp-THAE treatment of liver carcinoma. (authors)

Modified model of VX2 tumor overexpressing vascular endothelial growth factor.

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Pascale, Florentina; Ghegediban, Saida-Homayra; Bonneau, Michel; Bedouet, Laurent; Namur, Julien; Verret, Valentin; Schwartz-Cornil, Isabelle; Wassef, Michel; Laurent, Alexandre

2012-06-01

To determine whether upregulated expression of vascular endothelial growth factor (VEGF) in VX2 cells can increase vessel density (VD) and reduce tumor necrosis. The VX2 cell line was transfected with expression vectors containing cDNA for rabbit VEGF. Stable clones producing rabbit VEGF (VEGF-VX2) were selected. VEGF-VX2 cells (n = 5 rabbits) or nontransfected VX2 cells (controls; n = 5 rabbits) were implanted into leg muscle of 10 rabbits. The animals were sacrificed at day 21. Tumor volume, percentage of necrosis, VD, and VEGF concentration in tumor protein extract were quantified. Overexpression of VEGF by VX2 cells augmented tumor implantation efficiency 100% and favored cyst formation. The tumor volume was significantly larger for VEGF-VX2 transfected tumors versus controls (P = .0143). Overexpression of VEGF in VX2 cells significantly increased the VD of the tumors (P = .0138). The percentage of necrosis was reduced in VEGF-VX2 tumors versus controls (19.5% vs 38.5 %; P = .002). VEGF concentration in VEGF-VX2 tumors was significantly higher than in control tumors (P = .041) and was correlated with tumor volume (ρ = .883, P = .012). The overexpression of VEGF increased tumor growth and vascularization, favored cyst formation, and reduced tumor necrosis. This new phenotype of the VX2 tumor may offer some advantages over classic models of VX2 tumor for evaluating anticancer therapies. Copyright © 2012 SIR. Published by Elsevier Inc. All rights reserved.

Diffusion-weighted MR imaging allows monitoring the effect of combretastatin A4 phosphate on rabbit implanted VX2 tumor model: 12-Day dynamic results

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Shao Haibo; Ni Yicheng; Dai Xu; Zhang Jian; Chen Feng; Fan, Guoguang; Sun Ziping; Li Yaming; Zhou Hongxu; Xu Ke

2012-01-01

Objectives: To investigate the 12-day dynamic characteristics of tumor response to intravenous administration of CA4P in rabbit VX2 tumor models. Methods: Study protocol was approved by local ethical committee for animal care and use. Sixteen rabbits with 32 tumors on bilateral legs were randomly divided into treated and control groups. Conventional and DWI images were acquired before and 24 h, 4 days, 8 days and 12 days after treatment. The dynamic changes of tumor on images were correlated with histological results. ADCs were compared among and between groups at different time points. Results: The tumors in treated group grew slower than those in control group. In treaded group, the mean ADC decreased slightly at 24 h point due to cell edema caused by ischemia. Then, it increased significantly at 4 days and 8 days because of progressive central necrosis. Finally, peripheral tumor proliferation caused a second decrease of ADC at 12 days. The significant difference of ΔADC% between the two groups at 24 h, 4 days and 8 days indicated that the change of ADC in treated group was really caused by CA4P. Conclusion: The dynamic histological changes of tumor caused by CA4P as reflected exactly by diffusion-weighted MR imaging indicate a noninvasive measure for monitoring tumor vascular targeting treatment.

Contrast-enhanced MR imaging of hematogenous metastases of the VX2 tumor to the rabbit eye

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Frank, J.A.; Girton, M.; Dwyer, A.J.

1986-01-01

The authors have developed a reproducible model of hematogenous spread of malignancy to the eye of the rabbit. VX2 tumor cells (10/sup 6/ cells) were infused into the internal carotid artery of 15 New Zealand white rabbits weighting 2.5-3.5 kg. Ocular metastases developed in more than 90% of animals within 3-11 days. MR images were obtained 6-12 days after tumor inoculation (Picker, 0.5 T, saddle-shaped surface coil, 15-cm FOV, 5-mm section thickness). Tl-weighted SE550/40 images obtained after administration of Gd-DPTA (0.1) mmol/kg, given intravenously) demonstrated enhancement of aqueous humor due to disruption of the blood-ocular barrier and delineated tumor within the choroid. Metastases were confirmed at autopsy. The findings suggest the potential use of gadolinium-enhanced MR imaging for detecting ocular metastases and monitoring their growth

Combination of vascular endothelial growth factor antisense oligonucleotide therapy and radiotherapy increases the curative effects against maxillofacial VX2 tumors in rabbits

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Zheng Linfeng, E-mail: zhenglinfeng04@yahoo.com.cn [Department of Radiology, Shanghai First People' s Hospital, Medical College, Shanghai Jiaotong University, Hanning Road, 100, 200080 Shanghai (China); Li Yujie, E-mail: yujieli01@yahoo.com.cn [Department of Radiology, Shanghai First People' s Hospital, Medical College, Shanghai Jiaotong University, Hanning Road, 100, 200080 Shanghai (China); Wang Han, E-mail: bingowh@hotmail.com [Department of Radiology, Shanghai First People' s Hospital, Medical College, Shanghai Jiaotong University, Hanning Road, 100, 200080 Shanghai (China); Zhao Jinglong, E-mail: jinglongz@yahoo.com [Department of Radiology, Shanghai First People' s Hospital, Medical College, Shanghai Jiaotong University, Hanning Road, 100, 200080 Shanghai (China); Wang Xifu, E-mail: wangxiechen001@163.com [Department of Radiology, Shanghai First People' s Hospital, Medical College, Shanghai Jiaotong University, Hanning Road, 100, 200080 Shanghai (China); Hu Yunsheng, E-mail: springmorninghu@163.com [Department of Radiology, Shanghai First People' s Hospital, Medical College, Shanghai Jiaotong University, Hanning Road, 100, 200080 Shanghai (China); Zhang Guixiang, E-mail: guixiangzhang@sina.com [Department of Radiology, Shanghai First People' s Hospital, Medical College, Shanghai Jiaotong University, Hanning Road, 100, 200080 Shanghai (China)

2011-05-15

Purpose: To study the effects of combination of vascular endothelial growth factor (VEGF) antisense oligonucleotide therapy and radiotherapy on maxillofacial VX2 tumors in rabbits. Methods: We used 24 New Zealand white rabbits as a model to induce maxillofacial VX2 tumor. The rabbits were randomly divided into the following 4 groups: radiotherapy group (group A), treated with 16 Gy of radiotherapy; VEGF antisense oligonucleotide treatment group (group B), treated with an injection of 150 {mu}g of VEGF antisense oligonucleotide into the local tumor; VEGF antisense oligonucleotide combined with radiotherapy group (group C), treated with an injection of 150 {mu}g of VEGF antisense oligonucleotide into the local tumor immediately after 16 Gy of radiotherapy; and control group (group D), treated with an injection of 300 {mu}l 5% aqueous glucose solution into the local tumor. On days 3 and 14 after treatment, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was performed to calculate maximal enhancement ratio (MER), slope of enhancement (SLE), and tumor volume change. Rabbits were killed on day 14 to obtain samples for pathological examination and immunohistochemical staining for VEGF. Results: In group C, tumor volume was significantly reduced on day 14 after treatment, and the difference was statistically different as compared to that before treatment, on day 3 after treatment and other groups (P < 0.01). Values of both MER and SLE after treatment were significantly lower than the values before treatment (P < 0.05). Pathological specimen revealed tumor cell edema, bleeding, necrosis, vascular wall thickening and occlusion, and decreased VEGF expression. The immunohistochemical score (IHS) of group C was significantly different from groups A and D respectively (P < 0.05). Conclusion: Injecting the tumor with VEGF antisense oligonucleotide immediately after radiotherapy can enhance the curative effect on rabbit maxillofacial VX2 tumor, and DCE-MRI can serve

Establishment and identification of a rabbit model of peritoneal carcinomatosis from gastric cancer

International Nuclear Information System (INIS)

Mei, Lie-Jun; Yang, Xiao-Jun; Tang, Li; Hassan, Alaa Hammed al-shammaa; Yonemura, Yutaka; Li, Yan

2010-01-01

Gastric cancer peritoneal carcinomatosis is a common clinical problem, but there are no suitable large animal models to study this problem. This study was to establish a stable rabbit peritoneal carcinomatosis model of gastric cancer using VX2 tumor, and analyze the clinico-pathological features. VX2 tumor was implanted into 36 New Zealand rabbits by 3 methods: laparotomic orthotopic injection of cancer cells into the submucosal layer of the stomach (Group A), laparotomic implantation of tumor tissue into the greater omentum immediately beneath the gastric antrum (Group B), and percutaneous injection of tumor cells directly into the peritoneal cavity (Group C), 12 rabbits in each group. The animals were closely observed and detailed clinico-pathological studies were conducted. The success rates of peritoneal carcinomatosis formation were 100% (12/12), 91.7% (11/12) and 58.3% (7/12), respectively, for Groups A, B and C (P = 0.019, A versus C; P = 0.077, B versus C; P = 0.500, A versus B, Fisher's exact test). Two weeks after submucosal cancer cells injection in Group A, ulcerative gastric cancer with peritoneal carcinomatosis showed typical VX2 tumor pathology, with widespread intraperitoneal metastatic nodules, bloody ascites and perspicuous pulmonary metastases. The clinico-pathological progression pattern was very similar to patients of advanced gastric cancer with peritoneal carcinomatosis. Groups B and C showed similar pattern of cancer progression, but less aggressive. First large animal model of peritoneal carcinomatosis from gastric cancer has been established by laparotomic orthotopic injection of VX2 cancer cells into the submucosal layer of the stomach, providing a more suitable model for surgical interventional studies. The clinico-pathological features of this model resemble human peritoneal carcinomatosis

Targeting of VX2 Rabbit Liver Tumor by Selective Delivery of 3-Bromopyruvate: A Biodistribution and Survival Study

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Vali, Mustafa; Vossen, Josephina A.; Buijs, Manon; Engles, James M.; Liapi, Eleni; Ventura, Veronica Prieto; Khwaja, Afsheen; Acha-Ngwodo, Obele; Shanmugasundaram, Ganapathy; Syed, Labiq; Wahl, Richard L.; Geschwind, Jean-Francois H.

2009-01-01

The aim of this study was to determine the biodistribution and tumor targeting ability of 14C-labeled 3-bromopyruvate ([14C]3-BrPA) after i.a. and i.v. delivery in the VX2 rabbit model. In addition, we evaluated the effects of [14C]3-BrPA on tumor and healthy tissue glucose metabolism by determining 18F-deoxyglucose (FDG) uptake. Last, we determined the survival benefit of i.a. administered 3-BrPA. In total, 60 rabbits with VX2 liver tumor received either 1.75 mM [14C]3-BrPA i.a., 1.75 mM [14C]3-BrPA i.v., 20 mM [14C]3-BrPA i.v., or 25 ml of phosphate-buffered saline (PBS). All rabbits (with the exception of the 20 mM i.v. group) received FDG 1 h before sacrifice. Next, we compared survival of animals treated with i.a. administered 1.75 mM [14C]3-BrPA in 25 ml of PBS (n = 22) with controls (n = 10). After i.a. infusion, tumor uptake of [14C]3-BrPA was 1.8 ± 0.2% percentage of injected dose per gram of tissue (%ID/g), whereas other tissues showed minimal uptake. After i.v. infusion (1.75 mM), tumor uptake of [14C]3-BrPA was 0.03 ± 0.01% ID/g. After i.a. administration of [14C]3-BrPA, tumor uptake of FDG was 26 times lower than in controls. After i.v. administration of [14C]3-BrPA, there was no significant difference in tumor FDG uptake. Survival analysis showed that rabbits treated with 1.75 mM 3-BrPA survived longer (55 days) than controls (18.6 days). Intra-arterially delivered 3-BrPA has a favorable biodistribution profile, combining a high tumor uptake resulting in blockage of FDG uptake with no effects on healthy tissue. The local control of the liver tumor by 3-BrPA resulted in a significant survival benefit. PMID:18591216

Synchrotron radiation microimaging in rabbit models of cancer for preclinical testing

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Umetani, Keiji [Japan Synchrotron Radiation Research Institute, SPring-8, Sayo-cho, Sayo-gun, Hyogo 679-5198 (Japan)], E-mail: umetani@spring8.or.jp; Uesugi, Kentaro [Japan Synchrotron Radiation Research Institute, SPring-8, Sayo-cho, Sayo-gun, Hyogo 679-5198 (Japan); Kobatake, Makito; Yamamoto, Akira; Yamashita, Takenori; Imai, Shigeki [Kawasaki Medical School, Matsushima, Kurashiki-shi, Okayama 701-0192 (Japan)

2009-10-01

Preclinical laboratory animal imaging modalities such as microangiography and micro-computed tomography (micro-CT) have been developed at the SPring-8 BL20B2 bending magnet beamline. The objective of this paper is to demonstrate the usefulness of microangiography systems for physiological examinations of live animals and micro-CT systems for postmortem morphological examinations. Synchrotron radiation microangiography and micro-CT with contrast agents present the main advantageous capability of depicting the anatomy of small blood vessels with tens of micrometers' diameter. This paper reports two imaging instrument types and their respective applications to preclinical imaging of tumor angiogenic blood vessels in tumor-bearing rabbits, where tumor angiogenesis is characterized morphologically by an increased number of blood vessels. A microangiography system with spatial resolution around 10 {mu}m has been used for therapeutically evaluating angiogenic vessels in a rabbit model of cancer for evaluating embolization materials in transcatheter arterial embolization and for radiation therapy. After an iodine contrast agent was injected into an artery, in vivo imaging was carried out using a high-resolution real-time detector incorporating an X-ray direct-conversion-type SATICON pickup tube. On the other hand, a micro-CT system capably performed three-dimensional visualization of tumor angiogenic blood vessels using tumor-transplanted rabbit specimens with a barium sulfate contrast agent injected into the blood vessels. For specimen imaging, a large-field high-resolution micro-CT system based on a 10-megapixel CCD camera was developed to study tumor-associated alterations in angioarchitecture. Evidence of increased vascularity by tumor angiogenesis and decreased vascularity by tumor treatments was achieved by physiological evaluation of angiogenic small blood vessels in microangiographic imaging and by morphological assessment in micro-CT imaging. These results

Synchrotron radiation microimaging in rabbit models of cancer for preclinical testing

International Nuclear Information System (INIS)

Umetani, Keiji; Uesugi, Kentaro; Kobatake, Makito; Yamamoto, Akira; Yamashita, Takenori; Imai, Shigeki

2009-01-01

Preclinical laboratory animal imaging modalities such as microangiography and micro-computed tomography (micro-CT) have been developed at the SPring-8 BL20B2 bending magnet beamline. The objective of this paper is to demonstrate the usefulness of microangiography systems for physiological examinations of live animals and micro-CT systems for postmortem morphological examinations. Synchrotron radiation microangiography and micro-CT with contrast agents present the main advantageous capability of depicting the anatomy of small blood vessels with tens of micrometers' diameter. This paper reports two imaging instrument types and their respective applications to preclinical imaging of tumor angiogenic blood vessels in tumor-bearing rabbits, where tumor angiogenesis is characterized morphologically by an increased number of blood vessels. A microangiography system with spatial resolution around 10 μm has been used for therapeutically evaluating angiogenic vessels in a rabbit model of cancer for evaluating embolization materials in transcatheter arterial embolization and for radiation therapy. After an iodine contrast agent was injected into an artery, in vivo imaging was carried out using a high-resolution real-time detector incorporating an X-ray direct-conversion-type SATICON pickup tube. On the other hand, a micro-CT system capably performed three-dimensional visualization of tumor angiogenic blood vessels using tumor-transplanted rabbit specimens with a barium sulfate contrast agent injected into the blood vessels. For specimen imaging, a large-field high-resolution micro-CT system based on a 10-megapixel CCD camera was developed to study tumor-associated alterations in angioarchitecture. Evidence of increased vascularity by tumor angiogenesis and decreased vascularity by tumor treatments was achieved by physiological evaluation of angiogenic small blood vessels in microangiographic imaging and by morphological assessment in micro-CT imaging. These results

Percutaneous radiofrequency thermal ablation of lung VX2 tumors in a rabbit model: evaluation with helical CT findings for the complete and partal ablation

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Jin, Gong Yong; Han, Young Min; Lim, Yeong Su; Jang, Kyu Yun; Lee, Sang Yong; Chung, Gyung Ho [School of Medicine, Chonbuk National Univ., Chonju (Korea, Republic of)

2004-05-01

To evaluate the radiologic findings for complete and partial ablation after percutaneous CT-guided transthoracic radiofrequency ablation (RFA) of lung VX2 tumor implanted in rabbits. Thirteen rabbits with successfully implanted lung VX2 were used. Three rabbits as controls did not receive RFA while the other ten rabbits underwent RFA; 5 complete and 5 partial. RFA was performed using an internally cooled, 17-gauge electrode (Radionics, Burlington, MA) with a 1-cm active tip under CT guidance. Postprocedural CT was performed within 3 days, and we analyzed the ablated size, enhancement pattern, shape, margin, and complications of the complete and partial ablation groups. Rabbits were sacrificed after postprocedural CT with an overdose of ketamine, and pathologic findings of the ablated groups were compared with those of the control group. The size of the ablated lesions and the enhancement pattern differed between the completely and partially ablated groups on chest CT. The size of the ablated lesions was increased by 47.1% in the completely ablated group and by 2.1% in the partially ablated group. In the completely ablated group, VX2 tumor showed absolutely no enhancement, whereas only ablated pulmonary parenchyma outside VX2 showed mild enhancement on enhanced CT. In the partial ablated group, a part of VX2 became strongly enhanced on enhanced CT. On microscopic examination, the completely ablated group demonstrated that a viable tumor cell was not visible. In the partially ablated group, however, a viable tumor cell within the surrounding fibrous capsule on the peripheral area of the VX2 was observed. The important CT findings for evaluation of complete and partial RFA are the ablated size and enhancement pattern of the ablated lesion.

Whole-liver MR perfusion imaging in rabbit liver VX2 tumors: early findings of coagulative necrosis after percutaneous ethanol injection therapy

International Nuclear Information System (INIS)

Zhang Wanshi; Wang Dong; Meng Limin; Shi Huiping; Song Yunlong; Wu Bing

2007-01-01

Objective: To investigate the value of whole-liver MR perfusion imaging (MRPI) for early detection of coagulative necrosis after percutaneous ethanol injection (PEI) in rabbit liver VX 2 tumors. Methods: VX 2 tumor cell suspension was inoculated into rabbit liver and liver VX 2 tumors [diameter of (2.6 ± 0.6) cm] were induced in 10 male rabbits. MR T 1 WI and T 2 WI were performed to monitor the development of the liver tumor on the 2 nd and 3 rd week after inoculation. Whole-liver MRPI was performed in the 10 rabbits with liver VX 2 tumors before and 6 days after PEI therapy (1.0 ml ethanol was injected into the most enhanced tumor region under CT guiding). Signal intensity (SI) values of untreated tumor parts and treated areas 6 days after PEI were recorded respectively. The steepest slope (SS) and bolus arrival time (T0) of SI-time curves were measured. The t-Student test was used in statistical analysis of the data. Results: There was significant difference in MRPI data between untreated tumor parts [T0: (16.0 ± 1.2) s and SS: 38.9 ± 2.2] and treated areas [T0: (50.8 ± 5.9) s and SS: 6.0 ± 1.2] 6 days after PEI(t was 15.8 and -39.6 respectively, P 1 WI and T 2 WI could not show any differences between untreated tumor parts and treated areas. Conclusion: Whole-liver MRPI could detect coagulative necrosis of rabbit liver VX 2 tumors after PEI early. Disappearance of early enhancement can be a potential marker for efficacy of PEI. (authors)

[Effect of vascular endothelial growth factor and tumor necrosis factor receptor for treatment of avascular necrosis of the femoral head in rabbits].

Science.gov (United States)

Hu, Zhi-ming; Zhou, Ming-qian; Gao, Ji-min

2008-12-01

To evaluate the therapeutic effect of vascular endothelial growth factor (VEGF) and tumor necrosis factor receptor (TNFR) on avascular necrosis of the femoral head in rabbits. Avascular necrosis of the femoral head was induced in 26 New Zealand white rabbits by injections of horse serum and prednisolone. The rabbits were then divided into VEGF/TNFR treatment group, VEGF treatment group, and untreated model group, with another 4 normal rabbits as the normal control group. In the two treatment groups, the therapeutic agents were injected percutaneously into the femoral head. Enzyme-linked immunosorbent assay was performed to determine the concentration of TNF-alpha in rabbit serum followed by pathological examination of the changes in the bone tissues, bone marrow hematopoietic tissue and the blood vessels in the femoral head. Compared with the model group, the rabbits with both VEGF and TNFR treatment showed decreased serum concentration of TNF-alpha with obvious new vessel formation, decreased empty bone lacunae in the femoral head and hematopoietic tissue proliferation in the bone marrow cavity. Percutaneous injection of VEGF and TNFR into the femoral head can significantly enhance bone tissue angiogenesis and ameliorate osteonecrosis in rabbits with experimental femoral head necrosis.

Heated lipiodol as an embolization agent for transhepatic arterial embolization in VX2 rabbit liver cancer model

International Nuclear Information System (INIS)

Cao Wei; Wan Yi; Liang Zhihui; Duan Yunyou; Liu Xi; Wang Zhimin; Liu Yiyong; Zhu Jia; Liu Xiongtao; Zhang Hongxin

2010-01-01

Purpose: To evaluate the therapeutic effect of heated (60 deg. C) lipiodol via hepatic artery administration in a rabbit model of VX2 liver cancer. Materials and methods: Thirty male New Zealand white rabbits were randomly divided into three groups with 10 rabbits assigned to each group. VX2 carcinoma cells were surgically implanted into the left hepatic lobe. The tumors were allowed to grow for 2 weeks, and studies were performed until the diameter of the tumors detected by ultrasonograph reached 2-3 cm. Under anesthesia, trans-catheter hepatic arterial embolization was performed and doxorubicin-lipiodol (37 deg. C) (1 mL), lipiodol (60 deg. C) (1 mL) or control (physiological saline (37 deg. C) (1 mL)) solution was injected into the hepatic arteries of animals in the three groups. One week later, the volume of the tumor was measured by ultrasonograph again. The serum of all rabbits was collected before injection and at 4 and 7 days after injection, and the level of aspartate aminotransferase (AST) was checked. The survival period of the three groups of rabbits after treatment was also recorded. During the last course of their disease, the rabbits were given analgesics to relieve suffering. Results: The tumor growth rate in the lipiodol (60 deg. C) group (0.92 ± 0.21, tumor volume from 1811 ± 435 to 1670 ± 564 mm 3 ) was significantly lower than that in the control group (3.48 ± 1.17, tumor volume from 1808 ± 756 to 5747 ± 1341 mm 3 ) (P 3 ) (P -1 ) and the doxorubicin-lipiodol (37 deg. C) group (139.7 ± 12.3 U L -1 ) (P > 0.05). However, the serum AST level in the lipiodol (60 deg. C) group was significantly higher at 4 days after injection (P -1 ). Conclusions: Treatment with lipiodol (60 deg. C) resulted in an effect on serum AST levels similar to that caused by treatment with doxorubicin-lipiodol (37 deg. C). Thus, lipiodol (60 deg. C) treatment could greatly prolong the survival period of rabbits with VX2 cancer by inhibiting tumor growth.

[Effects of intra-arterial infusion of 3-bromopyruvate on metastases and survival benefit of hepatic VX2 tumor in rabbits].

Science.gov (United States)

Jiang, Xiong-ying; Zhang, Xiao-ping; Huang, Jin-hua; Luo, Rong-guang; Miao, Bi-jian; Wang, Yan

2013-10-22

To evaluate the metastasis and survival of an intra-arterial infusion of 3-bromopyruvate (3-BrPA) on hepatic VX2 tumor in rabbits. VX2 tumor was implanted in left lateral lobe of liver of 18 white New Zealand rabbits. The animals were randomized into 3 groups (n = 6 each) and underwent an intra-arterial infusion of phosphate-buffered saline or 3-BrPA via hepatic artery at 14 days post-implantation. At 28 days post-implantation, 3 rabbits in each group were sacrificed. The abdomen of these rabbits was opened and inspected for metastases. Then the survival of the remaining rabbits was observed. At 28 days post-implantation, in PBS group, there were intrahepatic metastasis and abdominal cavity dissemination (n = 3), renal metastases (n = 2) and lung metastases (n = 2); in early 3-BrPA infusion group, intrahepatic metastasis (n = 2), abdominal cavity dissemination (n = 1) and lung metastases (n = 1); in late 3-BrPA infusion group, intrahepatic metastasis (n = 1) and lung metastases (n = 1). The survival of the remaining animals was observed. Rabbits in early 3-BrPA infusion group survived significantly longer than those in PBS group [(27 ± 5) vs (17 ± 3) days, P = 0.041]; rabbits in late 3-BrPA infusion group [(42 ± 6) days] survived significantly longer than those in early 3-BrPA infusion group (P = 0.007). An intra-arterial infusion of 3-BrPA could reduce metastasis and prolong survival in rabbits with hepatic VX2 tumor. The earlier the infusion, the better the outcome.

Quantitative dual energy CT measurements in rabbit VX2 liver tumors: Comparison to perfusion CT measurements and histopathological findings

International Nuclear Information System (INIS)

Zhang, Long Jiang; Wu, Shengyong; Wang, Mei; Lu, Li; Chen, Bo; Jin, Lixin; Wang, Jiandong; Larson, Andrew C.; Lu, Guang Ming

2012-01-01

Purpose: To evaluate the correlation between quantitative dual energy CT and perfusion CT measurements in rabbit VX2 liver tumors. Materials and methods: This study was approved by the institutional animal care and use committee at our institution. Nine rabbits with VX2 liver tumors underwent contrast-enhanced dual energy CT and perfusion CT. CT attenuation for the tumors and normal liver parenchyma and tumor-to-liver ratio were obtained at the 140 kVp, 80 kVp, average weighted images and dual energy CT iodine maps. Quantitative parameters for the viable tumor and adjacent liver were measured with perfusion CT. The correlation between the enhancement values of the tumor in iodine maps and perfusion CT parameters of each tumor was analyzed. Radiation dose from dual energy CT and perfusion CT was measured. Results: Enhancement values for the tumor were higher than that for normal liver parenchyma at the hepatic arterial phase (P < 0.05). The highest tumor-to-liver ratio was obtained in hepatic arterial phase iodine map. Hepatic blood flow of the tumor was higher than that for adjacent liver (P < 0.05). Enhancement values of hepatic tumors in the iodine maps positively correlated with permeability of capillary vessel surface (r = 0.913, P < 0.001), hepatic blood flow (r = 0.512, P = 0.010), and hepatic blood volume (r = 0.464, P = 0.022) at the hepatic arterial phases. The effective radiation dose from perfusion CT was higher than that from DECT (P < 0.001). Conclusions: The enhancement values for viable tumor tissues measured in iodine maps were well correlated to perfusion CT measurements in rabbit VX2 liver tumors. Compared with perfusion CT, dual energy CT of the liver required a lower radiation dose.

Heated lipiodol as an embolization agent for transhepatic arterial embolization in VX2 rabbit liver cancer model

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Cao Wei [Department of Interventional Radiology, Tangdu Hospital, Fourth Military Medical University, No.1 Xinshi Road, Shaanxi Province, Xi' an 710038 (China)], E-mail: zjfurong2008@126.com; Wan Yi [Department of Health Statistics, Fourth Military Medical University, No. 17 West Changle Road, Xi' an 710032 (China); Liang Zhihui [Department of Radiology, Bethune International Peace Hospital, Shijiazhuang, Hebei Province 050082 (China); Duan Yunyou; Liu Xi [Department of Ultrasonography, Tangdu Hospital, Fourth Military Medical University, No. 1 Xinshi Road, Xi' an 710038 (China); Wang Zhimin; Liu Yiyong; Zhu Jia; Liu Xiongtao [Department of Interventional Radiology, Tangdu Hospital, Fourth Military Medical University, No.1 Xinshi Road, Shaanxi Province, Xi' an 710038 (China); Zhang Hongxin [Department of Interventional Radiology, Tangdu Hospital, Fourth Military Medical University, No.1 Xinshi Road, Shaanxi Province, Xi' an 710038 (China)], E-mail: cawe-001@163.com

2010-02-15

Purpose: To evaluate the therapeutic effect of heated (60 deg. C) lipiodol via hepatic artery administration in a rabbit model of VX2 liver cancer. Materials and methods: Thirty male New Zealand white rabbits were randomly divided into three groups with 10 rabbits assigned to each group. VX2 carcinoma cells were surgically implanted into the left hepatic lobe. The tumors were allowed to grow for 2 weeks, and studies were performed until the diameter of the tumors detected by ultrasonograph reached 2-3 cm. Under anesthesia, trans-catheter hepatic arterial embolization was performed and doxorubicin-lipiodol (37 deg. C) (1 mL), lipiodol (60 deg. C) (1 mL) or control (physiological saline (37 deg. C) (1 mL)) solution was injected into the hepatic arteries of animals in the three groups. One week later, the volume of the tumor was measured by ultrasonograph again. The serum of all rabbits was collected before injection and at 4 and 7 days after injection, and the level of aspartate aminotransferase (AST) was checked. The survival period of the three groups of rabbits after treatment was also recorded. During the last course of their disease, the rabbits were given analgesics to relieve suffering. Results: The tumor growth rate in the lipiodol (60 deg. C) group (0.92 {+-} 0.21, tumor volume from 1811 {+-} 435 to 1670 {+-} 564 mm{sup 3}) was significantly lower than that in the control group (3.48 {+-} 1.17, tumor volume from 1808 {+-} 756 to 5747 {+-} 1341 mm{sup 3}) (P < 0.05) and in the doxorubicin-lipiodol (37 deg. C) group (1.69 {+-} 0.26, tumor volume from 1881 {+-} 641 to 2428 {+-} 752 mm{sup 3}) (P < 0.05). Consequently, the survival period of the animals in the lipiodol (60 deg. C) group (41.0 {+-} 3.0 days) was significantly greater than that in the doxorubicin-lipiodol (37 deg. C) group (38.0 {+-} 2.5 days) (P < 0.05). On the other hand, there was no statistically significant difference in serum AST levels between the lipiodol (60 deg. C) group (148.2 {+-} 11

The evaluation of anti-angiogenic treatment effects for implanted rabbit VX2 breast tumors using functional multi-slice spiral computed tomography (f-MSCT)

International Nuclear Information System (INIS)

Lei Zhen; Ma Heji; Xu Na; Xi Huanjiu

2011-01-01

Objective: Investigate the benefit of functional multi-slice spiral computed tomography (f-MSCT) perfusion imaging in the non-invasive assessment of targeted anti-angiogenesis therapy on an implanted rabbit VX2 breast tumor model. Method: 69 female pure New Zealand white rabbits were randomly assigned to one of the 4 groups and received treatment accordingly: control (saline), Endostar, neoadjuvant chemotherapy (Cyclophosphamide, Epirubicin and 5-Fluorouracil, CEF), combination therapy (Endostar and CEF). After 2 weeks of treatment, f-MSCT perfusion scannings were performed for all rabbits and information about blood flow (BF), blood volume (BV), mean transit time (MTT) and surface permeability (SP) was collected. After perfusion imaging, tumor tissues were sampled for immunohistochemistry and the Western blot test of VEGF protein expression. Results: (1) The VEGF expression level, measured by immunohistochemistry and Western blot, decreased by treatment group (control > Endostar > CEF > combination therapy). The same was true for the mean BF, BV, MTT and PS, which decreased from the control group to the combination therapy group gradually. The mean MTT level increased in reverse order from the control to the combination therapy group. The difference between any 2 groups on these measures was statistically significant (P < 0.05). (2) There was moderate positive correlation between VEGF expression and BE, BV, or PS level (P < 0.05) and a negative correlation between VEGF expression and MTT level for all 4 groups (P < 0.05). Conclusion: Therefore, f-MSCT can be used as a non-invasive approach to evaluate the effect of anti-angiogenic therapy for implanted rabbit VX2 breast tumors.

The evaluation of anti-angiogenic treatment effects for implanted rabbit VX2 breast tumors using functional multi-slice spiral computed tomography (f-MSCT)

Energy Technology Data Exchange (ETDEWEB)

Lei Zhen, E-mail: leizhen2004@163.com [Department of Anatomy, Chinese Medical University, No. 92, Beiermalu Road, Heping District, Shenyang, 110001 (China) and Department of Radiology, The First Hospital of Liaoning Medical College, No. 2, Wuduan, Renmin Street, Jinzhou, 121001 (China); Ma Heji, E-mail: maheji9831@sina.com [Department of Radiology, The First Hospital of Liaoning Medical College, No. 2, Wuduan, Renmin Street, Jinzhou, 121001 (China); Xu Na, E-mail: xuna821230@sohu.com [Department of Radiology, The First Hospital of Liaoning Medical College, No. 2, Wuduan, Renmin Street, Jinzhou, 121001 (China); Xi Huanjiu, E-mail: xihuanjiu2004@yahoo.cn [Anthropology Institute, Liaoning Medical College, No. 40, Sanduan, Songpo Rd, Jinzhou, 121001 (China)

2011-05-15

Objective: Investigate the benefit of functional multi-slice spiral computed tomography (f-MSCT) perfusion imaging in the non-invasive assessment of targeted anti-angiogenesis therapy on an implanted rabbit VX2 breast tumor model. Method: 69 female pure New Zealand white rabbits were randomly assigned to one of the 4 groups and received treatment accordingly: control (saline), Endostar, neoadjuvant chemotherapy (Cyclophosphamide, Epirubicin and 5-Fluorouracil, CEF), combination therapy (Endostar and CEF). After 2 weeks of treatment, f-MSCT perfusion scannings were performed for all rabbits and information about blood flow (BF), blood volume (BV), mean transit time (MTT) and surface permeability (SP) was collected. After perfusion imaging, tumor tissues were sampled for immunohistochemistry and the Western blot test of VEGF protein expression. Results: (1) The VEGF expression level, measured by immunohistochemistry and Western blot, decreased by treatment group (control > Endostar > CEF > combination therapy). The same was true for the mean BF, BV, MTT and PS, which decreased from the control group to the combination therapy group gradually. The mean MTT level increased in reverse order from the control to the combination therapy group. The difference between any 2 groups on these measures was statistically significant (P < 0.05). (2) There was moderate positive correlation between VEGF expression and BE, BV, or PS level (P < 0.05) and a negative correlation between VEGF expression and MTT level for all 4 groups (P < 0.05). Conclusion: Therefore, f-MSCT can be used as a non-invasive approach to evaluate the effect of anti-angiogenic therapy for implanted rabbit VX2 breast tumors.

Investigations of a rabbit (Oryctolagus cuniculus model of systemic lupus erythematosus (SLE, BAFF and its receptors.

Directory of Open Access Journals (Sweden)

Jiahui Yang

2009-12-01

Full Text Available B-cell activation factor belonging to the tumor necrosis factor family (BAFF is a major contributor to survival of B lymphocytes during development and maturation. A relationship between circulating BAFF levels and disease activity has been reported in patients with the autoimmune disease Systemic Lupus Erythematosus (SLE. Clinical trials targeting BAFF or its receptors are currently in progress. In order to further characterize a rabbit (Oryctolagus cuniculus model of SLE, we investigated the expression of BAFF and its receptors in non-inbred, pedigreed rabbits derived from breeding and selection based on autoantibody responses. We immunized rabbits related to previous groups that developed autoantibodies and inflammatory responses after immunizations with peptides synthesized on multiple antigen-branched polylysine backbones. Blood and sera collected before immunization and after boosts were used for health monitoring, analyses of serum autoantibody responses by ELISA and immunofluorescence. Peripheral blood mononuclear cells (PBMC were studied by flow cytometry and were the source of mRNA for quantitative PCR analyses. We hypothesized that BAFF mRNA expression and serum BAFF levels measured indirectly through BAFF receptor binding might increase in autoantibody-producing rabbits. Immunized rabbits developed elevated levels of leucocyte populations, anti-nuclear, anti-dsDNA and other autoantibodies. BR3 mRNA levels in total PBMC decreased and BAFF levels remained low and unchanged in most immunized rabbits. By flow cytometry, percentages of BAFF positive cells decreased. Percentages of transmembrane activator and CAML interactor (TACI decreased in most rabbits from all the immunized groups. The rabbit is an important model for human autoimmune and infectious diseases, and a high quality draft rabbit genome assembly was recently completed. Human disease models developed in non-inbred pedigreed animals are better able to reflect the complexities

Rabbit tissue model (RTM) harvesting technique.

Science.gov (United States)

Medina, Marelyn

2002-01-01

A method for creating a tissue model using a female rabbit for laparoscopic simulation exercises is described. The specimen is called a Rabbit Tissue Model (RTM). Dissection techniques are described for transforming the rabbit carcass into a small, compact unit that can be used for multiple training sessions. Preservation is accomplished by using saline and refrigeration. Only the animal trunk is used, with the rest of the animal carcass being discarded. Practice exercises are provided for using the preserved organs. Basic surgical skills, such as dissection, suturing, and knot tying, can be practiced on this model. In addition, the RTM can be used with any pelvic trainer that permits placement of larger practice specimens within its confines.

Dynamic contrast-enhanced MRI using a macromolecular MR contrast agent (P792): Evaluation of antivascular drug effect in a rabbit VX2 liver tumor model

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Park, Hee Sun [Dept. of Radiology, Konkuk University School of Medicine, Seoul (Korea, Republic of); Han, Joon Koo; Lee, Jeong Min; Woo, Sung Min; Choi, Byung Ihn [Seoul National University Hospital, Seoul (Korea, Republic of); Kim, Young Il [Dept. of Radiology, Sheikh Khalifa Specialty Hospital, Ras Al Khaimah (United Arab Emirates); Choi, Jin Young [Dept. of Radiology, Yonsei University College of Medicine, Seoul (Korea, Republic of)

2015-10-15

To evaluate the utility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using macromolecular contrast agent (P792) for assessment of vascular disrupting drug effect in rabbit VX2 liver tumor models. This study was approved by our Institutional Animal Care and Use Committee. DCE-MRI was performed with 3-T scanner in 13 VX2 liver tumor-bearing rabbits, before, 4 hours after, and 24 hours after administration of vascular disrupting agent (VDA), using gadomelitol (P792, n = 7) or low molecular weight contrast agent (gadoterate meglumine [Gd-DOTA], n = 6). P792 was injected at a of dose 0.05 mmol/kg, while that of Gd-DOTA was 0.2 mmol/kg. DCE-MRI parameters including volume transfer coefficient (Ktrans) and initial area under the gadolinium concentration-time curve until 60 seconds (iAUC) of tumors were compared between the 2 groups at each time point. DCE-MRI parameters were correlated with tumor histopathology. Reproducibility in measurement of DCE-MRI parameters and image quality of source MR were compared between groups. P792 group showed a more prominent decrease in Ktrans and iAUC at 4 hours and 24 hours, as compared to the Gd-DOTA group. Changes in DCE-MRI parameters showed a weak correlation with histologic parameters (necrotic fraction and microvessel density) in both groups. Reproducibility of DCE-MRI parameters and overall image quality was not significantly better in the P792 group, as compared to the Gd-DOTA group. Dynamic contrast-enhanced magnetic resonance imaging using a macromolecular contrast agent shows changes of hepatic perfusion more clearly after administration of the VDA. Gadolinium was required at smaller doses than a low molecular contrast agent.

Dynamic contrast-enhanced MRI using a macromolecular MR contrast agent (P792): Evaluation of antivascular drug effect in a rabbit VX2 liver tumor model

International Nuclear Information System (INIS)

Park, Hee Sun; Han, Joon Koo; Lee, Jeong Min; Woo, Sung Min; Choi, Byung Ihn; Kim, Young Il; Choi, Jin Young

2015-01-01

To evaluate the utility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using macromolecular contrast agent (P792) for assessment of vascular disrupting drug effect in rabbit VX2 liver tumor models. This study was approved by our Institutional Animal Care and Use Committee. DCE-MRI was performed with 3-T scanner in 13 VX2 liver tumor-bearing rabbits, before, 4 hours after, and 24 hours after administration of vascular disrupting agent (VDA), using gadomelitol (P792, n = 7) or low molecular weight contrast agent (gadoterate meglumine [Gd-DOTA], n = 6). P792 was injected at a of dose 0.05 mmol/kg, while that of Gd-DOTA was 0.2 mmol/kg. DCE-MRI parameters including volume transfer coefficient (Ktrans) and initial area under the gadolinium concentration-time curve until 60 seconds (iAUC) of tumors were compared between the 2 groups at each time point. DCE-MRI parameters were correlated with tumor histopathology. Reproducibility in measurement of DCE-MRI parameters and image quality of source MR were compared between groups. P792 group showed a more prominent decrease in Ktrans and iAUC at 4 hours and 24 hours, as compared to the Gd-DOTA group. Changes in DCE-MRI parameters showed a weak correlation with histologic parameters (necrotic fraction and microvessel density) in both groups. Reproducibility of DCE-MRI parameters and overall image quality was not significantly better in the P792 group, as compared to the Gd-DOTA group. Dynamic contrast-enhanced magnetic resonance imaging using a macromolecular contrast agent shows changes of hepatic perfusion more clearly after administration of the VDA. Gadolinium was required at smaller doses than a low molecular contrast agent

Novel fluorescence nanobubbles for contrast-enhanced ultrasound imaging in rabbit VX2 hepatocellular carcinoma model

Science.gov (United States)

Yu, Houqiang; Wang, Wei; He, Xiaoling; Zhou, Qibing; Ding, Mingyue

2017-03-01

Ultrasound contrast agents (UCAs) such as SonoVue or Optison have been used widely in clinic for contrast-enhanced vascular imaging. However, microbubbles UCAs display limitations in tumor-targeted imaging due to the large sizes, nanoscaled UCAs has consequently attracted increasing attentions. In this work, we synthesized nanobubbles (NBs) by ultrasonic cavitation method, then a fluorescent marker of Alexa Fluor 680 was conjugated to the shell in order to observe the localization of NBs in tumor tissue. Measurement of fundamental characteristics showed that the NBs had homogeneous distribution of mean diameter of 267.9 +/- 19.2 nm and polydispersity index of 0.410 +/- 0.056. To assess in vivo tumor-selectivity of NBs, we established the rabbits VX2 hepatocellular carcinoma model though surgical implantation method. After the rabbits were intravenous administered of NBs, contrast-enhanced sonograms was observed in the surrounding of VX2 tumor, which showed there are rich capillaries in the tumor periphery. We additionally investigated the toxic of the NBs by hematoxylin-eosin staining. The results indicated that the NBs is a biocompatible non-toxic lipid system. Furthermore, the VX2 tumors and major organs were analyzed using ex vivo fluorescence imaging to confirm the targeted selectivity of NBs, and the results verified that the NBs were capable of targeting VX2 tumor. Confocal laser scanning microscopy examination showed that the NBs can traverse the VX2 tumor capillaries and target to the hepatocellular carcinoma tumor cells. All these results suggested that the newly prepared NBs have a potential application in molecular imaging and tumor-targeting therapy.

Evaluation for intravenous, arterial and local infusion of a hypoxic cell radiosensitizer RK28 on rabbit VX2 tumor system

International Nuclear Information System (INIS)

Kuramitsu, Tatsuya

1993-01-01

We evaluated the radiosensitizing effect of intraarterial, intravenous and local infusion of a hypoxic cell radiosensitizer RK28 on rabbit VX2 tumor system. Six rabbits were treated in each infusion group. VX2 tumor was implanted in the left hind leg. Tumor grown up to 3 cm in diameter was treated with 15 Gy of X-ray irradiation just after infusion of radiosensitizer RK28 (80 mg/kg.b.w.). Intratumoral and serum mean concentration of RK28 and its metabolites were measured. Tumor regression curve and survival time were analyzed. The following results were obtained. Mean concentration of RK28 was about 2.5 times greater in local infusion and 1.5 times in intraarterial infusion than in intravenous infusion. Significant regression of tumor was obtained in intraarterial infusion (p<0.01). There was no significant difference in survival time. These data suggest that the usefulness of intraarterial infusion of RK28 for local control using intraoperative radiation therapy and brachytherapy. (author)

MR staging of malignant musculoskeletal tumors: An experimental study on MR and pathologic correlation of rabbit VX-2 carcinoma

International Nuclear Information System (INIS)

Kang, Heung Sik; Chung, Sung Hoon; KIm, Cheol Woo; Kim, Seong Moon; Im, Jung Gi; Han, Man Chung

1993-01-01

To evaluate the reliability of MR imaging in tissue characterization and depiction of tumor boundaries, we performed MR pathologic correlation using parosteally implanted VX-2 carcinoma in 17 rabbit thighs. T1-weighted, T2-weighted and Gd-DTPA enhanced T1-weighted axial images were obtained 10-30 days after tumor implantation. After the animals were killed, frozen and sectioned along the MR imaging planes, and histopathologic examination were done. For accurate MR pathologic correlation, rabbit were fixed on the cardboard plate to minimize position change during the procedure. Tumor boundaries depicted on MR images were larger than those depicted on the specimen. Small tumors were surrounded by capsule-like loose connective tissue. Loose connective tissue became compact with tumor growth. This connective tissue showed high signal intensity on both T2-weighted and Gd-DTPA enhanced T1-weighted images. Muscle atrophy with fatty tissue accumulation around the tumor also contributed to the high signal intensity on MR images. Peritumoral edema and inflammatory reaction were not remarkable. Six of 8 cases with bone marrow fibrosis were detected on MR images. We concluded that peritumoral loose connective tissue and muscle atrophy exaggerated the size of experimentally induced malignant musculoskeletal tumors on MR images

Effect of Angelica Sinensis on liver fibrosis after radiotherapy combined with transarterial chemoembolization for rabbits with VX 2 tumor

International Nuclear Information System (INIS)

Long Qingyun; Zhou Yunfeng; Hu Jinxiang; Zhou Jun; Le Tao

2008-01-01

Objective: To evaluate the effect of Angelica Sinensis on liver fibrosis after radiotherapy (RT) combined with transarterial chemoembolization(TACE) for rabbits with VX 2 tumor, and the mechanism of anti-hepatic fibrosis. Methods: Fifty New Zealand white rabbits were divided randomly into three groups: Control group (n=10) was given saline 2 ml by gastroduodenal artery, model group (n=10) was given pingyangmycin 1 mg and iodized oil 0.2 ml, and exposed to single fraction of 20 Gy, Angelica group (n=30) undergoing RT combined with TACE was given Angelica Sinensis injection. According to different doses of Angelica Sinensis, Angelica group was divided into low-dose group (4 ml/kg), middle dose group (6 ml/kg) and high-dose group (8 ml/kg), twice per week for 4 weeks. Serum levels of HA, LN, PCIII, CIV and liver specimens were obtained at the end of 6th week after RT combined with TACE. The histological changes were determined by HE, VG staining and TGF-β1 immunohistochemistry staining. Results: Stages of liver fibrosis in the model group were mostly stages II and III, and stages of liver fibrosis in the Angelica group were mostly stages I, there was significant difference between the model group and the Angelica group, and stages of liver fibrosis were associated with Angelica intercention treatment (r=0.7631, P<0.01). Serum HA, LN, PCIII and CIV in the model group were higher than those in the control group(P<0.01), TGF-β1 expression in the Angelica group was significantly reduced compared with the wodel group and different doses of Angelica group showed dose-effect (r=0.4427, P<0.01). Conclusions: Angelica Sinensis injection has inhibitive effect on liver fibrosis after RT combined with TACE for rabbits with VX 2 tumor, the mechanism of anti-hepatic fibrosis might possibly be associated with down-regulating TGF-β1. (authors)

Effect of hyperthermia on blood flow in VX2 tumor transplanted in rabbit

International Nuclear Information System (INIS)

Arita, Takeshi

1994-01-01

Effect of hyperthermia on blood flow was evaluated using VX 2 rabbit carcinoma in both legs. Microwave energy at 2450 MHz was used to heat tumors for 40 minutes. An outer canula of 18 G Erasta was implanted in the depth of 2 cm in tumor to measure the temperature and to maintain at 43.0degC-44.0degC. The blood flow in tumors was evaluated by color doppler flow imaging and dynamic MRI. Disturbance of blood flow in the depth of surface 0 cm to 2 cm in tumors was showed at 10 minutes starting 43.0degC heating and at almost all sites disappearance of blood flow was showed at 40 minutes using color doppler flow imaging. But the blood flow beyond the depth of 2 cm was not so disturbed at 40 minutes, relatively. After hyperthermia T1WI and T2WI in heated tumor were no difference comparing with those in control tumor, but heated tumor showed no enhancement using dynamic MRI with TURBO-FLASH technique and post-enhanced T1WI. Histologically, there was extensive tumor necrosis and thrombus formation in heated tumor after 3 days and 1 week. Therefore color doppler flow imaging and dynamic MRI were considered to be useful for evaluation of blood flow in tumor after and during hyperthermia. (author)

Rabbit Model for Human EBV-Associated Hemophagocytic Syndrome (HPS)

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Hayashi, Kazuhiko; Jin, Zaishun; Onoda, Sachiyo; Joko, Hiromasa; Teramoto, Norihiro; Ohara, Nobuya; Oda, Wakako; Tanaka, Takehiro; Liu, Yi-Xuan; Koirala, Tirtha Raj; Oka, Takashi; Kondo, Eisaku; Yoshino, Tadashi; Takahashi, Kiyoshi; Akagi, Tadaatsu

2003-01-01

Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS) is often associated with fatal infectious mononucleosis or T-cell lymphoproliferative diseases (LPD). To elucidate the true nature of fatal LPD observed in Herpesvirus papio (HVP)-induced rabbit hemophagocytosis, reactive or neoplastic, we analyzed sequential development of HVP-induced rabbit LPD and their cell lines. All of the seven Japanese White rabbits inoculated intravenously with HVP died of fatal LPD 18 to 27 days after inoculation. LPD was also accompanied by hemophagocytic syndrome (HPS) in five of these seven rabbits. Sequential autopsy revealed splenomegaly and swollen lymph nodes, often accompanied by bleeding, which developed in the last week. Atypical lymphoid cells infiltrated many organs with a “starry sky” pattern, frequently involving the spleen, lymph nodes, and liver. HVP-small RNA-1 expression in these lymphoid cells was clearly demonstrated by a newly developed in situ hybridization (ISH) system. HVP-ISH of immunomagnetically purified lymphoid cells from spleen or lymph nodes revealed HVP-EBER1+ cells in each CD4+, CD8+, or CD79a+ fraction. Hemophagocytic histiocytosis was observed in the lymph nodes, spleen, bone marrow, and thymus. HVP-DNA was detected in the tissues and peripheral blood from the infected rabbits by PCR or Southern blot analysis. Clonality analysis of HVP-induced LPD by Southern blotting with TCR gene probe revealed polyclonal bands, suggesting polyclonal proliferation. Six IL-2-dependent rabbit T-cell lines were established from transplanted scid mouse tumors from LPD. These showed latency type I/II HVP infection and had normal karyotypes except for one line, and three of them showed tumorigenicity in nude mice. These data suggest that HVP-induced fatal LPD in rabbits is reactive polyclonally in nature. PMID:12707056

Quantification of drug-loaded magnetic nanoparticles in rabbit liver and tumor after in vivo administration

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Tietze, Rainer; Jurgons, Roland; Lyer, Stefan; Schreiber, Eveline [Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich-Alexander-University Erlangen-Nuernberg, Waldstr. 1, 91054 Erlangen (Germany); Wiekhorst, Frank; Eberbeck, Dietmar; Richter, Heike; Steinhoff, Uwe; Trahms, Lutz [Physikalisch-Technische Bundesanstalt, Berlin (Germany); Alexiou, Christoph [Department of Otorhinolaryngology, Head and Neck Surgery, Friedrich-Alexander-University Erlangen-Nuernberg, Waldstr. 1, 91054 Erlangen (Germany)], E-mail: C.Alexiou@web.de

2009-05-15

Magnetic nanoparticles have been investigated for biomedical applications for more than 30 years. The development of biocompatible nanosized drug delivery systems for specific targeting of therapeutics is imminent in medical research, especially for treating cancer and vascular diseases. We used drug-labeled magnetic iron oxide nanoparticles, which were attracted to an experimental tumor in rabbits with an external magnetic field (magnetic drug targeting, MDT). Aim of this study was to detect and quantify the biodistribution of the magnetic nanoparticles by magnetorelaxometry. The study shows higher amount of nanoparticles in the tumor after intraarterial application and MDT compared to intravenous administration.

Comparative study of rabbit VX2 hepatic implantation tumor and normal liver tissue on magnetic resonance perfusion weighted imaging

International Nuclear Information System (INIS)

Jiao Zimei; Wang Xizhen; Wang Bin; Liu Feng; Li Haiqing; Sun Yequan; Dong Peng

2012-01-01

Objective: To investigate the value of magnetic resonance (MR) perfusion weighted imaging (PWI) in evaluating the blood perfusion of tumor by analyzing the features and indexes of PWI on rabbit VX2 hepatic implantation tumor and normal liver tissue. Methods: Twenty-four New Zealand White rabbits with VX2 carcinoma were established under direct surgical vision embedding tumor tissue. MR examination was performed at 21 days after the tumor implantation. The signal intensity -time curve of hepatic tumor and normal liver tissue were obtained. Mean time to enhance (MTE), negative enhancement integral (NEI), time to minimum (TM), maximum slope of decrease (MSD) and maximum slope of increase (MSI) were measured. Results: MTE, NEI, TM, MSD, and MSI of the normal liver tissue were 208.341±2.226 ms, 78.334±8.152, 24.059±1.927 ms, 38.221±2.443, and 15.389±2.526, respectively. MTE, NEI, TM, MSD, and MSI of the tumor tissue were 175.437±4.182 ms, 123.203±19.455, 17.061±1.834 ms, 125.740±4.842, and 67.832±2.882, respectively. The MTE and TM of tumor were shorter than those of normal hepatic tissue (P<0.05). NEI, MSD, and MSI of tumor were higher than those of normal hepatic tissue (P<0.05). Conclusion: PWI can distinguish the normal liver tissue from the tumor tissue, which is helpful in evaluating blood perfusion of different hepatic tissues. (authors)

Animal in vivo models of EBV-associated lymphoproliferative diseases: special references to rabbit models.

Science.gov (United States)

Hayashi, K; Teramoto, N; Akagi, T

2002-10-01

Animal models of human EBV-associated diseases are essential to elucidate the pathogenesis of EBV-associated diseases. Here we review those previous models using EBV or EBV-like herpesviruses and describe the details on our two newly-developed rabbit models of lymphoproliferative diseases (LPD) induced by simian EBV-like viruses. The first is Cynomolgus-EBV-induced T-cell lymphomas in rabbits inoculated intravenously (77-90%) and orally (82-89%) during 2-5 months. EBV-DNA was detected in peripheral blood by PCR from 2 days after oral inoculation, while anti-EBV-VCA IgG was raised 3 weeks later. Rabbit lymphomas and their cell lines contained EBV-DNA and expressed EBV-encoded RNA-1 (EBER-1). Rabbit lymphoma cell lines, most of which have specific chromosomal abnormality, showed tumorigenicity in nude mice. The second is the first animal model for EBV-infected T-cell LPD with virus-associated hemophagocytic syndrome (VAHS), using rabbits infected with an EBV-like herpesvirus, Herpesvirus papio (HVP). Rabbits inoculated intravenously with HVP-producing cells showed increased anti-EBV-VCA-IgG titers, and most (85%) subsequently died of fatal LPD and VAHS, with bleeding and hepatosplenomegaly, during 22-105 days. Peroral spray of cell-free HVP induced viral infection with seroconversion in 3 out of 5 rabbits, with 2 of the 3 infected rabbits dying of LPD with VAHS. Atypical T lymphocytes containing HVP-DNA and expressing EBER-1 were observed in many organs. Hemophagocytic histiocytosis was observed in the lymph nodes, spleen, bone marrow, and thymus. These rabbit models are also useful and inexpensive alternative experimental model systems for studying the biology and pathogenesis of EBV, and prophylactic and therapeutic regimens.

Pharmacokinetics and Histopathological Findings of Chemoembolization Using Cisplatin Powder Mixed with Degradable Starch Microspheres in a Rabbit Liver Tumor Model

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Sato, Takeshi; Tanaka, Toshihiro, E-mail: toshihir@bf6.so-net.ne.jp; Nishiofuku, Hideyuki; Fukuoka, Yasushi [IVR CenterNara Medical University, Department of Radiology (Japan); Sakaguchi, Hiroshi [South Nara General Medical Center, Department of Radiology (Japan); Masada, Tetsuya; Tatsumoto, Shota [IVR CenterNara Medical University, Department of Radiology (Japan); Marugami, Nagaaki [Diagnostic Imaging Center, Department of Radiology (Japan); Takano, Masato [Nara Medical University, Department of Diagnostic Pathology (Japan); Yamato, Ichiro; Sho, Masayuki [Nara Medical University, Department of Surgery (Japan); Ohbayashi, Chiho [Nara Medical University, Department of Diagnostic Pathology (Japan); Hirai, Toshiko [Diagnostic Imaging Center, Department of Radiology (Japan); Kichikawa, Kimihiko [IVR CenterNara Medical University, Department of Radiology (Japan)

2017-03-15

PurposeThe purpose of this study is to evaluate the pharmacokinetics and histopathological findings of transarterial chemoembolization (TACE) using cisplatin powder mixed with degradable starch microspheres (DSM) (Cis/DSM-TACE) compared with cisplatin arterial infusion (Cis-AI).Materials and MethodsEighteen rabbits with VX2 liver tumors were divided into two groups: Cis/DSM-TACE (n = 9) and Cis-AI (n = 9) groups. In the Cis/DSM-TACE group, a mixture of cisplatin powder and DSM was injected until stasis of hepatic arterial flow was achieved. In the Cis-AI group, cisplatin solution was infused.ResultsThe platinum concentrations in VX2 tumors in the Cis/DSM-TACE group at 24 and 72 h were significantly elevated compared with those in the Cis-AI group (P = .016 and .019, respectively). There were no significant differences in the platinum concentrations in plasma. Histopathological examination revealed the presence of several microspheres inside the tumors at 1 h, which completely disappeared at 24 h. Tumor cell apoptosis at 1 h in the Cis/DSM-TACE group was more frequently observed compared with that in the Cis-AI group (P = .006).ConclusionsTACE using cisplatin powder mixed with DSM provides a higher drug concentration in tumors, thereby achieving stronger antitumor effects compared with arterial infusion of cisplatin solution.

Pharmacokinetics and Histopathological Findings of Chemoembolization Using Cisplatin Powder Mixed with Degradable Starch Microspheres in a Rabbit Liver Tumor Model

International Nuclear Information System (INIS)

Sato, Takeshi; Tanaka, Toshihiro; Nishiofuku, Hideyuki; Fukuoka, Yasushi; Sakaguchi, Hiroshi; Masada, Tetsuya; Tatsumoto, Shota; Marugami, Nagaaki; Takano, Masato; Yamato, Ichiro; Sho, Masayuki; Ohbayashi, Chiho; Hirai, Toshiko; Kichikawa, Kimihiko

2017-01-01

PurposeThe purpose of this study is to evaluate the pharmacokinetics and histopathological findings of transarterial chemoembolization (TACE) using cisplatin powder mixed with degradable starch microspheres (DSM) (Cis/DSM-TACE) compared with cisplatin arterial infusion (Cis-AI).Materials and MethodsEighteen rabbits with VX2 liver tumors were divided into two groups: Cis/DSM-TACE (n = 9) and Cis-AI (n = 9) groups. In the Cis/DSM-TACE group, a mixture of cisplatin powder and DSM was injected until stasis of hepatic arterial flow was achieved. In the Cis-AI group, cisplatin solution was infused.ResultsThe platinum concentrations in VX2 tumors in the Cis/DSM-TACE group at 24 and 72 h were significantly elevated compared with those in the Cis-AI group (P = .016 and .019, respectively). There were no significant differences in the platinum concentrations in plasma. Histopathological examination revealed the presence of several microspheres inside the tumors at 1 h, which completely disappeared at 24 h. Tumor cell apoptosis at 1 h in the Cis/DSM-TACE group was more frequently observed compared with that in the Cis-AI group (P = .006).ConclusionsTACE using cisplatin powder mixed with DSM provides a higher drug concentration in tumors, thereby achieving stronger antitumor effects compared with arterial infusion of cisplatin solution.

Changes of serum IL-2, IL-4, IL-10 and IFN-γ levels after treatment with 131I-17-allylamino-17-demethoxygeldanamycin in VX2 rabbit models

International Nuclear Information System (INIS)

Gao Wen; Liu Lu; Zhou Yun

2007-01-01

Objective: To study the influence of 131 I-17-allylamino-17-demethoxygeldanamycin( 131 I-17-AAG) therapy on immune function in VX2 rabbit models with transplanted liver cancer. Methods: Serum IL-2, IL-4, IL-10 and IFN-γ levels were measured with RIA in 8 VX2 rabbit models with transplanted liver cancer 1-2 weeks after 10mCi 131 I-17-AAG treatment as well as in 8 controls rabbits (models with tumor but without treatment). Results: 1 week after 10mCi 131 I treatment, the serum IL - 2 and IFN-γ levels were significantly lower in the treated rabbits than those in controls (P 0.05). Serum IL-4 and IL-10 levels in the treated rabbits (both at 1 and 2 week) were not significantly different from those in controls (P>0.05). Conclusion: 131 I-17-AAG treatment had transient effects on cellular immunity with no influence on humoral immunity. As a whole, it is a safe to treat VX2 rabbit models with this preparation. (authors)

Brachytherapy Using Elastin-Like Polypeptides with (131)I Inhibit Tumor Growth in Rabbits with VX2 Liver Tumor.

Science.gov (United States)

Liu, Xinpei; Shen, Yiming; Zhang, Xuqian; Lin, Rui; Jia, Qiang; Chang, Yixiang; Liu, Wenge; Liu, Wentian

2016-10-01

Brachytherapy is a targeted type of radiotherapy utilized in the treatment of cancers. Elastin-like polypeptides are a unique class of genetically engineered peptide polymers that have several attractive properties for brachytherapy. To explore the feasibility and application of brachytherapy for VX2 liver tumor using elastin-like polypeptides with (131)I so as to provide reliable experimental evidence for a new promising treatment of liver cancer. Elastin-like polypeptide as carrier was labeled with (131)I using the iodogen method. Ten eligible rabbits with VX2 liver tumor were randomly divided into the treatment group (n = 5) and control group (n = 5). The treatment group received brachytherapy using elastin-like polypeptide with (131)I, and in the control group, elastin-like polypeptide was injected into the VX2 liver tumor as a control. Periodic biochemical and imaging surveillances were required to assess treatment efficacy. The stability of elastin-like polypeptide with (131)I in vitro was maintained at over 96.8 % for 96 h. Biochemistry and imaging indicated brachytherapy using elastin-like polypeptide with (131)I for liver tumor can improve liver function and inhibit tumor growth (P Elastin-like polypeptide can be an ideal carrier of (131)I and have high labeling efficiency, radiochemical purity and stability. Brachytherapy using elastin-like polypeptide with (131)I for liver tumor is a useful therapy that possesses high antitumor efficacy advantages.

Development of a Zealand white rabbit deposition model to study inhalation anthrax

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Asgharian, Bahman; Price, Owen; Kabilan, Senthil; Jacob, Richard E.; Einstein, Daniel R.; Kuprat, Andrew P.; Corley, Richard A.

2016-01-28

Despite using rabbits in several inhalation exposure experiments to study diseases such as anthrax, there is a lack of understanding regarding deposition characteristics and fate of inhaled particles (bio-aerosols and viruses) in the respiratory tracts of rabbits. Such information allows dosimetric extrapolation to humans to inform human outcomes. The lung geometry of the New Zealand white rabbit (referred to simply as rabbits throughout the article) was constructed using recently acquired scanned images of the conducting airways of rabbits and available information on its acinar region. In addition, functional relationships were developed for the lung and breathing parameters of rabbits as a function of body weight. The lung geometry and breathing parameters were used to extend the existing deposition model for humans and several other species to rabbits. Evaluation of the deposition model for rabbits was made by comparing predictions with available measurements in the literature. Deposition predictions in the lungs of rabbits indicated smaller deposition fractions compared to those found in humans across various particle diameter ranges. The application of the deposition model for rabbits was demonstrated by extrapolating deposition predictions in rabbits to find equivalent human exposure concentrations assuming the same dose-response relationship between the two species. Human equivalent exposure concentration levels were found to be much smaller than those for rabbits.

Intravascular application of electrocautery in a rabbit model of abdominal aortic endarterectomy.

Science.gov (United States)

Wang, Chuan; Xin, Yi; Li, Na; Li, Diankun; Li, Jingxing; Gu, Chengxiong

2017-07-01

Effective therapies for preventing perioperative complications such as thrombosis and inflammation after coronary endarterectomy (CE) are lacking. Electrocoagulation electrotomes have been routinely used in surgery for their cutting, clotting, and hemostatic properties. As strong flattening tools, their electrocautery function may prevent mechanical intimal-adventitial injury to arterial circulation and attenuate stenosis. The present study investigated the effects of intravascular application of electrocautery on ameliorating inflammation and thrombosis in a rabbit model of abdominal aortic endarterectomy. New Zealand rabbits were randomly divided into the sham, control (endarterectomy), and study (endarterectomy + electrocautery) groups with 10 in each group. Abdominal aortas were partially blocked and intima was removed. Electrocautery was performed with an electrocoagulation electrotome through the entire blocked vessel lumen. Vascular ultrasound parameters, molecular biological and histological characteristics of the abdominal aorta including vascular diameter, blood flow velocity, serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels, and apoptosis rate of vascular endothelial cells (ECs) were evaluated postoperatively by vascular Doppler ultrasound, ELISA, real-time RT-PCR, flow cytometry, and immunofluorescence at various time points. Compared with the endarterectomy + electrocautery group, the isolated endarterectomy group had significantly increased levels and gene expression of TNF-α and IL-6 (Pelectrocautery has favorable short-term effects on the abdominal aorta and can reduce inflammation in a rabbit model of abdominal aorta endarterectomy. Long-term anti-inflammatory and anti-thrombotic effects on arterial remodeling and the clinical value of electrocautery in CE remain to be determined.

Creating a Long-Term Diabetic Rabbit Model

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Jianpu Wang

2010-01-01

Full Text Available This study was to create a long-term rabbit model of diabetes mellitus for medical studies of up to one year or longer and to evaluate the effects of chronic hyperglycemia on damage of major organs. A single dose of alloxan monohydrate (100 mg/kg was given intravenously to 20 young New Zealand White rabbits. Another 12 age-matched normal rabbits were used as controls. Hyperglycemia developed within 48 hours after treatment with alloxan. Insulin was given daily after diabetes developed. All animals gained some body weight, but the gain was much less than the age-matched nondiabetic rabbits. Hyperlipidemia, higher blood urea nitrogen and creatinine were found in the diabetic animals. Histologically, the pancreas showed marked beta cell damage. The kidneys showed significantly thickened afferent glomerular arterioles with narrowed lumens along with glomerular atrophy. Lipid accumulation in the cytoplasm of hepatocytes appeared as vacuoles. Full-thickness skin wound healing was delayed. In summary, with careful management, alloxan-induced diabetic rabbits can be maintained for one year or longer in reasonably good health for diabetic studies.

Development of a Zealand White Rabbit Deposition Model to Study Inhalation Anthrax

Science.gov (United States)

Asgharian, Bahman; Price, Owen; Kabilan, Senthil; Jacob, Richard E.; Einstein, Daniel R.; Kuprat, A.P.; Corley, Richard A.

2016-01-01

Despite using rabbits in several inhalation exposure experiments to study diseases such as anthrax, there is a lack of understanding regarding deposition characteristics and fate of inhaled particles (bio-aerosols and viruses) in the respiratory tracts of rabbits. Such information allows dosimetric extrapolation to humans to inform human outcomes. The lung geometry of the New Zealand white rabbit (referred to simply as rabbits throughout the article) was constructed using recently acquired scanned images of the conducting airways of rabbits and available information on its acinar region. In addition, functional relationships were developed for the lung and breathing parameters of rabbits as a function of body weight. The lung geometry and breathing parameters were used to extend the existing deposition model for humans and several other species to rabbits. Evaluation of the deposition model for rabbits was made by comparing predictions with available measurements in the literature. Deposition predictions in the lungs of rabbits indicated smaller deposition fractions compared to those found in humans across various particle diameter ranges. The application of the deposition model for rabbits was demonstrated by extrapolating deposition predictions in rabbits to find equivalent human exposure concentrations assuming the same dose-response relationship between the two species. Human equivalent exposure concentration levels were found to be much smaller than those for rabbits. PMID:26895308

Investigation in clinical potential of polarization sensitive optical coherence tomography in laryngeal tumor model study

Science.gov (United States)

Zhou, Xin; Oak, Chulho; Ahn, Yeh-Chan; Kim, Sung Won; Tang, Shuo

2018-02-01

Polarization-sensitive optical coherence tomography (PS-OCT) is capable of measuring tissue birefringence. It has been widely applied to access the birefringence in tissues such as skin and cartilage. The vocal cord tissue consists of three anatomical layers from the surface to deep inside, the epithelium that contains almost no collagen, the lamina propria that is composed with abundant collagen, and the vocalis muscle layer. Due to the variation in the organization of collagen fibers, the different tissue layers show different tissue birefringence, which can be evaluated by PS-OCT phase retardation measurement. Furthermore, collagen fibers in healthy connective tissues are usually well organized, which provides relatively high birefringence. When the collagen organization is destroyed by diseases such as tumor, the birefringence of the tissue will decrease. In this study, a rabbit laryngeal tumor model with different stages of tumor progression is investigated ex-vivo by PS-OCT. The PS-OCT images show a gradual decrease in birefringence from normal tissue to severe tumor tissue. A phase retardation slope-based analysis is conducted to distinguish the epithelium, lamina propria, and muscle layers, respectively. The phase retardation slope quantifies the birefringence in different layers. The quantitative study provides a more detailed comparison among different stages of the rabbit laryngeal tumor model. The PS-OCT result is validated by the corresponding histology images of the same samples.

A dynamic study of correlation between the MR diffusion weighted imaging findings and the expression of proliferation-related and metastasis-related genes in rabbit models of liver VX2 tumor before and after chemoembolization

International Nuclear Information System (INIS)

Yuan Youhong; Liu Jianbin; Xiao Enhua; He Zhong; Ma Cong; Xiang Jun; Jin Ke; Chen Wenjian; Xiao Jiehua

2007-01-01

Objective: To investigate the correlation between the apparent diffusion coefficient (ADC) values and the expression of proliferating cell nuclear antigen (PCNA), Bax, non-metastasis 23(nm23) and E-cadherin (E-cad) genes in rabbit models of liver VX 2 tumor before and after chemoembolization. Methods: Forty rabbit models of liver VX 2 tumor were divided into four groups with 10 rabbits in each group. The first group was the control group which didn't undergo chemoembolization. The second, third and fourth groups underwent chemoembolization, and diffusion weighted imaging (DWI) was performed at 16 h, 32 h and 48 h after chemoembolization respectively. The pathological and immunohistological examinations were carried out right after DWI. The sampling areas included the normal liver parenchyma around the tumor, the outer- layer area, the peripheral area, and the central area. The expression indices of PCNA, Bax, nm23, E-cad in all the samples were recorded and their correlation with corresponding ADC value were analyzed. Results: (1) PCNA expression indices in the outer layer area, the peripheral area and central area of VX 2 tumors(65.1%, 74.7%, and 59.0% respectively) were higher than that in the area of normal parenchyma around tumor (8.3%) (X 2 =19.08, P 2 tumors (nm 23: 1.7%, 0.4% , and 6.2% respectively; Bax: 2. 0%, 1.2% , and 2. 2% respectively; E-cad:6.2%, 2.0%, and 1.6% respectively) were lower than that in the area of normal parenchyma around tumor (nm23 16.5%; Bax 40.0%; E-cad 78.0%. χ 2 =12.86, 20.17, and 22.20 respectively; P 2 tumor periphery were 83.0%, 92.6% and 85.7% in 16 h group, 32 h group and 48 h group respectively after chemoembolization and those of nm23 expression indices were 2.3%, 7.4%, 4.2% and those of Bax expression index were 0.8%, 0.5%, 0.9% and those of E-cad expression indices were 2.8%, 1.0%, 1.1%. The PCNA and nm23 expression in the area of VX 2 tumor periphery increased at the beginning and then decreased (χ 2 =14.37, 8.94; P 2

Early quantification of the therapeutic efficacy of the vascular disrupting agent, CKD-516, using dynamic contrast-enhanced ultrasonography in rabbit VX2 liver tumors

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Joo, Ijin; Kim, Jung Hoon; Lee, Jeong Min; Choi, Jin Woo; Han, Joon Koo; Choi, Byung Ihn [Dept. of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of)

2014-03-15

To evaluate the usefulness of dynamic contrast-enhanced ultrasonography (DCE-US) in the early quantification of hemodynamic change following administration of the vascular disrupting agent (VDA) CKD-516 using a rabbit VX2 liver tumor model. This study was approved by our institutional animal care and use committee. Eight VX2 liver-tumor-bearing rabbits were treated with intravenous CKD-516, and all underwent DCE-US using SonoVue before and again 2, 4, 6, and 24 hours following their treatment. The tumor perfusion parameters were obtained from the time-intensity curve of the DCE-US data. Repeated measures analysis of variance was performed to assess any significant change in tumor perfusion over time. Relative changes in the DCE-US parameters between the baseline and follow-up assessments were correlated with the relative changes in tumor size over the course of seven days using Pearson correlation. CKD-516 treatment resulted in significant changes in the DCE-US parameters, including the peak intensity, total area under the time-intensity curve (AUCtotal), and AUC during wash-out (AUCout) over time (P<0.05). Pairwise comparison tests revealed that the AUCtotal and AUC during wash-in (AUCin) seen on the two-hour follow-up were significantly lower than the baseline values (P<0.05). However, none of early changes in the DCE-US parameters until 24-hour follow-up showed a significant correlation with the relative changes in tumor size during seven days after CKD-516 treatment. Our results suggest that a novel VDA (CKD-516) can cause disruption of tumor perfusion as early as two hours after treatment and that the therapeutic effect of CKD-516 treatment can be effectively quantified using DCE-US.

A comparison of perfusion computed tomography and contrast enhanced computed tomography on radiation target volume delineation using rabbit VX2 brain tumor model

International Nuclear Information System (INIS)

Sun Changjin; Luo Yunxiu; Yu Jinming; Lu Haibo; Li Chao; Zhang Dekang; Huang Jianming; Wang Jie; Lang Jinyi

2010-01-01

Objective: To compare the accuracy of blood volume perfusion imaging (perfusion CT)with contrast enhanced 64-slice spiral computed tomography (CECT) in the evaluation of gross tumor volume (GTV) and clinical target volume (CTV) using rabbits with VX2 brain tumor. Methods: Perfusion CT and CECT were performed in 20 rabbits with VX2 brain tumor. The GTV and CTV calculated with the maximal and minimal diameter of each tumor in the blood volume (BV) maps and CECT were measured and compared to those in pathological specimens. Results: The mean value of the maximal and minimal diameter of GTV was (8.19 ± 2.29) mm and (4.83 ± 1.31) mm in pathological specimens, (11.98 ±3.29) mm and (7.03±1.82) mm in BV maps, while (6.36±3.85) mm and (3.17±1.93) mm in CECT images, which were significantly different (pathological specimen vs. BV map, t = 7.17, P =0.000;pathological specimen vs. CECT, t = 8.37, P = 0.000, respectively). The mean value of the maximal and minimal diameter of CTV in pathologic specimens was (12.87 ± 3.74) mm and (7.71 ± 2.15) mm, which was significantly different from that of GTV and CTV in CECT (t = - 3. 18, P = 0. 005 and t = - 4.24, P =0.000; t= -11.59,P=0.000 and t= -9.39, P=0.000), while similar with that of GTV in BV maps (t = - 1.95,P = 0. 067; t = - 2. 06, P = 0. 054). For CECT, the margin from GTV to CTV was 81.83% ±40.33% for the maximal diameter and 276.73% ± 131.46% for the minimal. While for BV maps, the margin was 7.93% ± 17. 84% and 12.52% ± 27. 83%, which was significant different from that for CECT images (t=7.36, P=0. 000 and t= -8.78, P=0.000). Conclusions: Compared with CECT, the BV map from 64-slice spiral CT perfusion imaging might have higher accuracy in target volume delineation for brain tumor. (authors)

A rabbit model of non-typhoidal Salmonella bacteremia.

Science.gov (United States)

Panda, Aruna; Tatarov, Ivan; Masek, Billie Jo; Hardick, Justin; Crusan, Annabelle; Wakefield, Teresa; Carroll, Karen; Yang, Samuel; Hsieh, Yu-Hsiang; Lipsky, Michael M; McLeod, Charles G; Levine, Myron M; Rothman, Richard E; Gaydos, Charlotte A; DeTolla, Louis J

2014-09-01

Bacteremia is an important cause of morbidity and mortality in humans. In this study, we focused on the development of an animal model of bacteremia induced by non-typhoidal Salmonella. New Zealand White rabbits were inoculated with a human isolate of non-typhoidal Salmonella strain CVD J73 via the intra-peritoneal route. Blood samples were collected at specific time points and at euthanasia from infected rabbits. Additionally, tissue samples from the heart, lungs, spleen, gastrointestinal tract, liver and kidneys were obtained at euthanasia. All experimentally infected rabbits displayed clinical signs of disease (fever, dehydration, weight loss and lethargy). Tissues collected at necropsy from the animals exhibited histopathological changes indicative of bacteremia. Non-typhoidal Salmonella bacteria were detected in the blood and tissue samples of infected rabbits by microbiological culture and real-time PCR assays. The development of this animal model of bacteremia could prove to be a useful tool for studying how non-typhoidal Salmonella infections disseminate and spread in humans. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Effects of Irreversible Electroporation on the Achilles Tendon: An Experimental Study in a Rabbit Model.

Directory of Open Access Journals (Sweden)

Yue Song

Full Text Available To evaluate the potential effects of irreversible electroporation ablation on the Achilles tendon in a rabbit model and to compare the histopathological and biomechanical changes between specimens following electroporation ablation and radiofrequency ablation.A total of 140 six-month-old male New Zealand rabbits were used. The animals were randomly divided into two groups, 70 in the radiofrequency ablation group and 70 in the electroporation group. In situ ablations were applied directly to the Achilles tendons of rabbits using typical electroporation (1800 V/cm, 90 pulses and radiofrequency ablation (power control mode protocols. Histopathological and biomechanical evaluations were performed to examine the effects of electroporation ablation and radiofrequency ablation over time.Both electroporation and radiofrequency ablation produced complete cell ablation in the target region. Thermal damage resulted in tendon rupture 3 days post radiofrequency ablation. In contrast, electroporation-ablated Achilles tendons preserved their biomechanical properties and showed no detectable rupture at this time point. The electroporation-ablated tendons exhibited signs of recovery, including tenoblast regeneration and angiogenesis within 2 weeks, and the restoration of their integral structure was evident within 12 weeks.When applying electroporation to ablate solid tumors, major advantage could be that collateral damage to adjacent tendons or ligaments is minimized due to the unique ability of electroporation ablation to target the cell membrane. This advantage could have a significant impact on the field of tumor ablation near vital tendons or ligaments.

The Effects of Irreversible Electroporation on the Achilles Tendon: An Experimental Study in a Rabbit Model.

Science.gov (United States)

Song, Yue; Zheng, Jingjing; Yan, Mingwei; Ding, Weidong; Xu, Kui; Fan, Qingyu; Li, Zhao

2015-01-01

To evaluate the potential effects of irreversible electroporation ablation on the Achilles tendon in a rabbit model and to compare the histopathological and biomechanical changes between specimens following electroporation ablation and radiofrequency ablation. A total of 140 six-month-old male New Zealand rabbits were used. The animals were randomly divided into two groups, 70 in the radiofrequency ablation group and 70 in the electroporation group. In situ ablations were applied directly to the Achilles tendons of rabbits using typical electroporation (1800 V/cm, 90 pulses) and radiofrequency ablation (power control mode) protocols. Histopathological and biomechanical evaluations were performed to examine the effects of electroporation ablation and radiofrequency ablation over time. Both electroporation and radiofrequency ablation produced complete cell ablation in the target region. Thermal damage resulted in tendon rupture 3 days post radiofrequency ablation. In contrast, electroporation-ablated Achilles tendons preserved their biomechanical properties and showed no detectable rupture at this time point. The electroporation-ablated tendons exhibited signs of recovery, including tenoblast regeneration and angiogenesis within 2 weeks, and the restoration of their integral structure was evident within 12 weeks. When applying electroporation to ablate solid tumors, major advantage could be that collateral damage to adjacent tendons or ligaments is minimized due to the unique ability of electroporation ablation to target the cell membrane. This advantage could have a significant impact on the field of tumor ablation near vital tendons or ligaments.

Assessing Anticalcification Treatments in Bioprosthetic Tissue by Using the New Zealand Rabbit Intramuscular Model

Science.gov (United States)

Wright, Gregory A; Faught, Joelle M; Olin, Jane M

2009-01-01

The objective of this work was to demonstrate that the New Zealand White (NZW) rabbit intramuscular model can be used for detecting calcification in bioprosthetic tissue and to compare the calcification in the rabbit to that of native human valves. The rabbit model was compared with the commonly used Sprague–Dawley rat subcutaneous model. Eighteen rabbits and 18 rats were used to assess calcification in bioprosthetic tissue over time (7, 14, 30, and 90 d). The explanted rabbit and rat tissue discs were measured for calcium by using atomic absorption and Raman spectroscopy. Calcium deposits on the human valve explants were assessed by using Raman spectroscopy. The results showed that the NZW rabbit model is robust for detecting calcification in a shorter duration (14 d), with less infection complications, more space to implant tissue groups (thereby reducing animal use numbers), and a more metabolically and mechanically dynamic environment than the rat subcutaneous model . The human explanted valves and rabbit explanted tissue both showed Raman peaks at 960 cm−1 which is representative of hydroxyapatite. Hydroxyapatite is the final calcium and phosphate species in the calcification of bioprosthetic heart valves and rabbit intramuscular implants. The NZW rabbit intramuscular model is an effective model for assessing calcification in bioprosthetic tissue. PMID:19619417

Rabbit models for the study of human atherosclerosis: from pathophysiological mechanisms to translational medicine.

Science.gov (United States)

Fan, Jianglin; Kitajima, Shuji; Watanabe, Teruo; Xu, Jie; Zhang, Jifeng; Liu, Enqi; Chen, Y Eugene

2015-02-01

Laboratory animal models play an important role in the study of human diseases. Using appropriate animals is critical not only for basic research but also for the development of therapeutics and diagnostic tools. Rabbits are widely used for the study of human atherosclerosis. Because rabbits have a unique feature of lipoprotein metabolism (like humans but unlike rodents) and are sensitive to a cholesterol diet, rabbit models have not only provided many insights into the pathogenesis and development of human atherosclerosis but also made a great contribution to translational research. In fact, rabbit was the first animal model used for studying human atherosclerosis, more than a century ago. Currently, three types of rabbit model are commonly used for the study of human atherosclerosis and lipid metabolism: (1) cholesterol-fed rabbits, (2) Watanabe heritable hyperlipidemic rabbits, analogous to human familial hypercholesterolemia due to genetic deficiency of LDL receptors, and (3) genetically modified (transgenic and knock-out) rabbits. Despite their importance, compared with the mouse, the most widely used laboratory animal model nowadays, the use of rabbit models is still limited. In this review, we focus on the features of rabbit lipoprotein metabolism and pathology of atherosclerotic lesions that make it the optimal model for human atherosclerotic disease, especially for the translational medicine. For the sake of clarity, the review is not an attempt to be completely inclusive, but instead attempts to summarize substantial information concisely and provide a guideline for experiments using rabbits. Copyright © 2014 Elsevier Inc. All rights reserved.

Validation of transport measurements in skeletal muscle with N-13 amino acids using a rabbit isolated hindlimb model

International Nuclear Information System (INIS)

Conlon, K.C.; Bading, J.R.; DiResta, G.R.; Corbally, M.T.; Gelbard, A.S.; Brennan, M.F.

1989-01-01

The authors are studying the transport of C-11 and N-13 labeled amino acids in tumor-bearing rabbits to determine the role of amino acid transport in the pathogenesis of muscle wasting in cancer. To validate a new, in vivo, method for measuring transport in skeletal muscle with these compounds, an isolated hindlimb model was developed in rabbits. The limb was perfused with a non-recirculating, normothermic, constant pressure system and a cell-free perfusate. Hemodynamic and metabolic parameters were measured during the first 75 min. of perfusion and found to remain normal and stable. Flow varied directly with perfusion pressure over the normal range of resting flows in the intact rabbit hindlimb. Time-activity curves (TAC's) were recorded from the medial thigh following bolus co-injection of L-[amide N-13] glutamine or N-13 L-glutamate with Tc-99m human serum albumin (HSA) into the femoral artery. Regional plasma flow was determined from the Tc-99m data

The use of rabbits in atherosclerosis research. Diet and drug intervention in different rabbit models exposed to selected dietary fats and the calcium antagonist (-)-anipamil

DEFF Research Database (Denmark)

Mortensen, Alicja

Laboratory animal models play an important role in atherosclerosis research. One of the most popular laboratory animal species in this field of research is the rabbit. The rabbit fulfils most of the criteria for an animal model for human atherosclerosis. Three rabbit models were established...

Role of interleukin 1 and tumor necrosis factor on energy metabolism in rabbits

International Nuclear Information System (INIS)

Tredget, E.E.; Yu, Y.M.; Zhong, S.; Burini, R.; Okusawa, S.; Gelfand, J.A.; Dinarello, C.A.; Young, V.R.; Burke, J.F.

1988-01-01

A study of the combined effects of intravenous infusion of the recombinant cytokines beta-interleukin 1 (IL-1) and alpha-tumor necrosis factor (TNF) on energy substrate metabolism in awake, conditioned, adult rabbits was performed. After a 2-h basal or control period, 48-h fasted rabbits were administered TNF and IL-1 as a bolus (5 micrograms/kg) followed by a continuous intravenous infusion (25 ng.kg-1.min-1) for 3 h. Significant increases in plasma lactate (P less than 0.01), glucose (P less than 0.01), and triglycerides (P less than 0.05) occurred during the combined infusion of IL-1 and TNF, whereas neither cytokine alone had no effect. There was a 33% increase in the rate of glucose appearance (P less than 0.05), but glucose clearance was not altered compared with the control period. Glucose oxidation increased during the combined cytokine infusion period and glucose recycling increased by 600% (P less than 0.002). Lactic acidosis and decreased oxygen consumption, as a result of the cytokine infusions, indicated development of anaerobic glycolytic metabolism. A reduction in the activity state of hepatic mitochondrial pyruvate dehydrogenase (65 vs. 82% in control animals, P less than 0.05) was consistent with the observed increase in anaerobic glycolysis. Thus the combined infusion of IL-1 and TNF in rabbits produces metabolic manifestations seen in severe injury and sepsis in human patients and, as such, may account for the profound alterations of energy metabolism seen in these conditions

Role of interleukin 1 and tumor necrosis factor on energy metabolism in rabbits

Energy Technology Data Exchange (ETDEWEB)

Tredget, E.E.; Yu, Y.M.; Zhong, S.; Burini, R.; Okusawa, S.; Gelfand, J.A.; Dinarello, C.A.; Young, V.R.; Burke, J.F.

1988-12-01

A study of the combined effects of intravenous infusion of the recombinant cytokines beta-interleukin 1 (IL-1) and alpha-tumor necrosis factor (TNF) on energy substrate metabolism in awake, conditioned, adult rabbits was performed. After a 2-h basal or control period, 48-h fasted rabbits were administered TNF and IL-1 as a bolus (5 micrograms/kg) followed by a continuous intravenous infusion (25 ng.kg-1.min-1) for 3 h. Significant increases in plasma lactate (P less than 0.01), glucose (P less than 0.01), and triglycerides (P less than 0.05) occurred during the combined infusion of IL-1 and TNF, whereas neither cytokine alone had no effect. There was a 33% increase in the rate of glucose appearance (P less than 0.05), but glucose clearance was not altered compared with the control period. Glucose oxidation increased during the combined cytokine infusion period and glucose recycling increased by 600% (P less than 0.002). Lactic acidosis and decreased oxygen consumption, as a result of the cytokine infusions, indicated development of anaerobic glycolytic metabolism. A reduction in the activity state of hepatic mitochondrial pyruvate dehydrogenase (65 vs. 82% in control animals, P less than 0.05) was consistent with the observed increase in anaerobic glycolysis. Thus the combined infusion of IL-1 and TNF in rabbits produces metabolic manifestations seen in severe injury and sepsis in human patients and, as such, may account for the profound alterations of energy metabolism seen in these conditions.

Experimental and finite element analysis of tibial stress fractures using a rabbit model.

Science.gov (United States)

Franklyn, Melanie; Field, Bruce

2013-01-01

To determine if rabbit models can be used to quantify the mechanical behaviour involved in tibial stress fracture (TSF) development. Fresh rabbit tibiae were loaded under compression using a specifically-designed test apparatus. Weights were incrementally added up to a load of 30 kg and the mechanical behaviour of the tibia was analysed using tests for buckling, bone strain and hysteresis. Structural mechanics equations were subsequently employed to verify that the results were within the range of values predicted by theory. A finite element (FE) model was developed using cross-sectional computer tomography (CT) images scanned from one of the rabbit bones, and a static load of 6 kg (1.5 times the rabbit's body weight) was applied to represent running. The model was validated using the experimental strain gauge data, then geometric and elemental convergence tests were performed in order to find the minimum number of cross-sectional scans and elements respectively required for convergence. The analysis was then performed using both the model and the experimental results to investigate the mechanical behaviour of the rabbit tibia under compressive load and to examine crack initiation. The experimental tests showed that under a compressive load of up to 12 kg, the rabbit tibia demonstrates linear behaviour with little hysteresis. Up to 30 kg, the bone does not fail by elastic buckling; however, there are low levels of tensile stress which predominately occur at and adjacent to the anterior border of the tibial midshaft: this suggests that fatigue failure occurs in these regions, since bone under cyclic loading initially fails in tension. The FE model predictions were consistent with both mechanics theory and the strain gauge results. The model was highly sensitive to small changes in the position of the applied load due to the high slenderness ratio of the rabbit's tibia. The modelling technique used in the current study could have applications in the development of

The model of pulmonary embolism caused by autologous thrombus in rabbits

OpenAIRE

Yu-Jiao Ding; Yang Chen

2017-01-01

Objective: To establish a model of pulmonary embolism in rabbits by using autologous thrombosis of rabbit ear vein, to study the method of establishing acute pulmonary embolism by using autologous thrombus and to explore the diagnostic value of oxygen partial pressure in acute pulmonary embolism. Methods: Twenty rabbits were randomly divided into normal group (n=5), 7 h group, 24h group, 1 week after model establishment Group. The arterial blood gas analysis was performed on th...

Comparison of lung protective ventilation strategies in a rabbit model of acute lung injury.

Science.gov (United States)

Rotta, A T; Gunnarsson, B; Fuhrman, B P; Hernan, L J; Steinhorn, D M

2001-11-01

To determine the impact of different protective and nonprotective mechanical ventilation strategies on the degree of pulmonary inflammation, oxidative damage, and hemodynamic stability in a saline lavage model of acute lung injury. A prospective, randomized, controlled, in vivo animal laboratory study. Animal research facility of a health sciences university. Forty-six New Zealand White rabbits. Mature rabbits were instrumented with a tracheostomy and vascular catheters. Lavage-injured rabbits were randomized to receive conventional ventilation with either a) low peak end-expiratory pressure (PEEP; tidal volume of 10 mL/kg, PEEP of 2 cm H2O); b) high PEEP (tidal volume of 10 mL/kg, PEEP of 10 cm H2O); c) low tidal volume with PEEP above Pflex (open lung strategy, tidal volume of 6 mL/kg, PEEP set 2 cm H2O > Pflex); or d) high-frequency oscillatory ventilation. Animals were ventilated for 4 hrs. Lung lavage fluid and tissue samples were obtained immediately after animals were killed. Lung lavage fluid was assayed for measurements of total protein, elastase activity, tumor necrosis factor-alpha, and malondialdehyde. Lung tissue homogenates were assayed for measurements of myeloperoxidase activity and malondialdehyde. The need for inotropic support was recorded. Animals that received a lung protective strategy (open lung or high-frequency oscillatory ventilation) exhibited more favorable oxygenation and lung mechanics compared with the low PEEP and high PEEP groups. Animals ventilated by a lung protective strategy also showed attenuation of inflammation (reduced tracheal fluid protein, tracheal fluid elastase, tracheal fluid tumor necrosis factor-alpha, and pulmonary leukostasis). Animals treated with high-frequency oscillatory ventilation had attenuated oxidative injury to the lung and greater hemodynamic stability compared with the other experimental groups. Both lung protective strategies were associated with improved oxygenation, attenuated inflammation, and

The Rabbit as a Model for Studying Lung Disease and Stem Cell Therapy

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Nurfatin Asyikhin Kamaruzaman

2013-01-01

Full Text Available No single animal model can reproduce all of the human features of both acute and chronic lung diseases. However, the rabbit is a reliable model and clinically relevant facsimile of human disease. The similarities between rabbits and humans in terms of airway anatomy and responses to inflammatory mediators highlight the value of this species in the investigation of lung disease pathophysiology and in the development of therapeutic agents. The inflammatory responses shown by the rabbit model, especially in the case of asthma, are comparable with those that occur in humans. The allergic rabbit model has been used extensively in drug screening tests, and this model and humans appear to be sensitive to similar drugs. In addition, recent studies have shown that the rabbit serves as a good platform for cell delivery for the purpose of stem-cell-based therapy.

Rabbit models of cerebral vasospasm established with endovascular puncture

International Nuclear Information System (INIS)

Tu Jianfei; Liu Yizhi; Ji Jiansong; Zhao Zhongwei

2008-01-01

Objective: To investigate the method of endovascular puncture to establish rabbit models of cerebral vasospasm. Methods: New Zealand white rabbits were divided into 5 groups (12 h, 1 d, 2 d, 3 d and 7 d) randomly, and each group was separated into subarachnoid hemorrhage (SAH) subgroup (n=5) and control subgroup (n=2). cerebral vascular spasm (CVS) models were established after SAH with endovascular puncture. CT scans before and after operation were performed. The internal diameters and the wall thicknesses of posterior communicans artery (PcoA) and basilar artery (BA) were measured with HE stain after the animals were executed. Results: CVS model was successfully eastblished in 35 rabbits (SAH subgroup 25, control subgroup 10), resulting a successful rate of 48.61%. Compared with control subgroup, PcoA and BA showed shrinkage of internal diameters of 43.60% and 51.82% 12 h after SAH, respectively, and the shrinkage appeared as biphasic patterns until the 7th study day with another peaks of 29.32% and 45.19%, respectively. Conclusions: Endovascular puncture is an effective method to establish rabbit of CVS. The death rate of animals can be decreased with the asage of new interventional material and perfection for the details of operation. (authors)

The Effect of Induced Antibodies with Respect to Neutralization, Clearance Rate and Functional Activity in a Rabbit/Infliximab Model

DEFF Research Database (Denmark)

Henriksen, Maiken Lumby; Søgaard Teisner, Ane; Kjeldsen, Jens

2016-01-01

BACKGROUND: Therapeutic antibodies are a developing field for treatment of an expanding number of inflammatory diseases, including Crohn's disease. Treatment with monoclonal antibodies is frequently hampered by development of anti-drug antibodies (ADAs) that may compromise the treatment. MATERIALS...... AND METHODS: We addressed this issue in a rabbit model of treatment with the anti-tumor-necrosis factor alpha (TNFα) antibody, infliximab (IFX). We developed an inhibition ELISA to selectively measure absolute concentrations of neutralizing antibodies and another ELISA for measuring the concentration...... of functional IFX in the circulation. RESULTS: We found that the concentration of functional IFX was inversely proportional to the concentration of neutralizing antibodies. CONCLUSION: Administration of IFX to rabbits showed diversity in immune responses/tolerance toward IFX, corresponding to responses observed...

Efficacy and safety of 32P-nanocolloid for treatment of distant lymph node metastasis in VX2 tumor-bearing rabbits

International Nuclear Information System (INIS)

Dong Shengxiang; Huang Gang; Liu Penan; Ma Yubo; Yan Weili; Wan Liangrong; Zhu Changqing

2008-01-01

Eradication of micrometastases present in lymph nodes of cancer patients improves their prognosis significantly. Radionuclide therapy possesses the potential to eliminate such metastases. This study was performed to evaluate the efficacy and safety of 32 P-nanocolloid therapy in the treatment of distant carcinoma cell metastases in lymph nodes of VX2 tumor-bearing rabbits. The Method of this study was to obtain VX2 tumor micrometastases in right armpit lymph nodes of 12 male New Zealand white rabbits, VX2 tumors were implanted by hypodermal inoculation into the right anterior limb. Animals were randomly divided into therapy (n=6) and control (n=6) groups. 32 P-nanocolloid (0.5 mCi), 95% of which was >50 nm in diameter, was administered to the therapy group, and saline was administered to the control group. Injections were given once weekly for 4 weeks. 2-Deoxy-2[ 18 F]-fluoro-D-glucose positron emission tomography revealed that the number of involved lymph nodes and the maximum standardized uptake value decreased in the 32 P-nanocolloid therapy group as compared with the baseline or saline control group (P 32 P-nanocolloid. These findings support treatment with 32 P-nanocolloid as a safe and effective approach for eradication of lymph node micrometastases. (author)

Hemocoagulase Combined with Microbubble-Enhanced Ultrasound Cavitation for Augmented Ablation of Microvasculature in Rabbit VX2 Liver Tumors.

Science.gov (United States)

Yang, Qian; Tang, Peng; He, Guangbin; Ge, Shuping; Liu, Liwen; Zhou, Xiaodong

2017-08-01

We investigated a new method for combining microbubble-enhanced ultrasound cavitation (MEUC) with hemocoagulase (HC) atrox. Our goal was to induce embolic effects in the vasculature and combine these with an anti-angiogenic treatment strategy. Fourteen days after being implanted with a single slice of the liver VX2 tumor, rabbits were randomly divided into five groups: (i) a control group injected intra-venously with saline using a micropump; (ii) a group given only an injection of HC; (iii) a group treated only with ultrasound cavitation; (iv) a group treated with MEUC; (v) a group treated with MEUC + HC. Contrast-enhanced ultrasound was performed before treatment and 1 h and 7 d post-treatment to measure tumor size, enhancement and necrosis range. QontraXt software was used to determine the time-intensity curve of tumor blood perfusion and microvascular changes. At 1 h and 7 d after treatment with MEUC + HC, the parameters of the time-intensity curve, which included peak value, regional blood volume, regional blood flow and area under the curve value and which were measured using contrast-enhanced ultrasound, were significantly lower than those of the other treatment groups. The MEUC + HC treatment group exhibited significant growth inhibition relative to the ultrasound cavitation only, HC and MEUC treatment groups. No damage was observed in the surrounding normal tissues. These results support the feasibility of reducing the blood perfusion of rabbit VX2 liver tumors using a new method that combines MEUC and HC. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. All rights reserved.

Tumor vascularity of experimentally induced VX2 carcinoma in the rabbit thigh: evaluation with enhanced power doppler sonography and DSA correlated with histopathologic findings

Energy Technology Data Exchange (ETDEWEB)

Kim, Young Hoon; Han, Joon Koo; Chung, Jin Wook; Lee, Kyoung Ho; Kim, Se Hyung; Kim, Seog Joon; Choi, Byung Ihn; Chang, Kee Hyun [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)

2002-05-01

To describe findings of enhanced power Doppler sonography and DSA in experimentally induced VX2 carcinomas in rabbit thigh and to correlate the imaging findings with the histopathologic features. A total of 30 VX2 carcinomas were implanted in rabbit thigh, and after conventional and enhanced power Doppler sonography and DSA, histopathologic examination was performed. Enhanced power Doppler sonography and DSA, were used to determine the distribution pattern of tumor vascularity; to assess its grade and the percentage of a tumor area occupied by vessels, conventional and enhanced power Doppler sonography, as well as DSA, were used. The grade of necrosis and the development of fibrovascular stroma and capsule were histopathologically determined. The findings of power Doppler sonography were compared with those of DSA and the imaging features were correlated with the histopathologic features. At enhanced power Doppler sonography, the signal was either avascular (n=9), peripheral (n=15) or diffuse (n=6), while at DSA, the corresponding totals were eight, fourteen and eight. There was statistically significant corelation between enhanced power Doppler sonogrpahy and DSA, both in their depiction of the distribution of patterns of tumor vascularity and as regards their findings of grade and percentage of vascular area. As determined by both conventional and enhanced power Doppler sonogrpahy, and by DSA, grade of necrosis and the development of fibrovascular stroma and a capsule correlated with grade and the percentage of vascular area. Experimentally induced VX2 carcinomas in rabbit thigh demonstrated various patterns of tumor vascularity, and the findings of enhanced power Doppler sonography correlated with those of DSA. Tumor vascularity, as demonstrated by two imaging modalities, correlated closely with grade of necrosis and the development of fibrovascular stroma and a capsule, as revealed by histopathologic examination.

Tumor vascularity of experimentally induced VX2 carcinoma in the rabbit thigh: evaluation with enhanced power doppler sonography and DSA correlated with histopathologic findings

International Nuclear Information System (INIS)

Kim, Young Hoon; Han, Joon Koo; Chung, Jin Wook; Lee, Kyoung Ho; Kim, Se Hyung; Kim, Seog Joon; Choi, Byung Ihn; Chang, Kee Hyun

2002-01-01

To describe findings of enhanced power Doppler sonography and DSA in experimentally induced VX2 carcinomas in rabbit thigh and to correlate the imaging findings with the histopathologic features. A total of 30 VX2 carcinomas were implanted in rabbit thigh, and after conventional and enhanced power Doppler sonography and DSA, histopathologic examination was performed. Enhanced power Doppler sonography and DSA, were used to determine the distribution pattern of tumor vascularity; to assess its grade and the percentage of a tumor area occupied by vessels, conventional and enhanced power Doppler sonography, as well as DSA, were used. The grade of necrosis and the development of fibrovascular stroma and capsule were histopathologically determined. The findings of power Doppler sonography were compared with those of DSA and the imaging features were correlated with the histopathologic features. At enhanced power Doppler sonography, the signal was either avascular (n=9), peripheral (n=15) or diffuse (n=6), while at DSA, the corresponding totals were eight, fourteen and eight. There was statistically significant corelation between enhanced power Doppler sonogrpahy and DSA, both in their depiction of the distribution of patterns of tumor vascularity and as regards their findings of grade and percentage of vascular area. As determined by both conventional and enhanced power Doppler sonogrpahy, and by DSA, grade of necrosis and the development of fibrovascular stroma and a capsule correlated with grade and the percentage of vascular area. Experimentally induced VX2 carcinomas in rabbit thigh demonstrated various patterns of tumor vascularity, and the findings of enhanced power Doppler sonography correlated with those of DSA. Tumor vascularity, as demonstrated by two imaging modalities, correlated closely with grade of necrosis and the development of fibrovascular stroma and a capsule, as revealed by histopathologic examination

The Rabbit as a Model for Studying Lung Disease and Stem Cell Therapy

OpenAIRE

Kamaruzaman, Nurfatin Asyikhin; Kardia, Egi; Kamaldin, Nurulain ‘Atikah; Latahir, Ahmad Zaeri; Yahaya, Badrul Hisham

2013-01-01

No single animal model can reproduce all of the human features of both acute and chronic lung diseases. However, the rabbit is a reliable model and clinically relevant facsimile of human disease. The similarities between rabbits and humans in terms of airway anatomy and responses to inflammatory mediators highlight the value of this species in the investigation of lung disease pathophysiology and in the development of therapeutic agents. The inflammatory responses shown by the rabbit model, e...

Quantification of HTLV-I proviral load in experimentally infected rabbits

Directory of Open Access Journals (Sweden)

Kindt Thomas J

2005-05-01

Full Text Available Abstract Background Levels of proviral load in HTLV-1 infected patients correlate with clinical outcome and are reasonably prognostic. Adaptation of proviral load measurement techniques is examined here for use in an experimental rabbit model of HTLV-1 infection. Initial efforts sought to correlate proviral load with route and dose of inoculation and with clinical outcome in this model. These methods contribute to our continuing goal of using the model to test treatments that alleviate virus infection. Results A real-time PCR assay was used to measure proviral load in blood and tissue samples from a series of rabbits infected using HTLV-1 inocula prepared as either cell-free virus particles, infected cells or blood, or by naked DNA injection. Proviral loads from asymptomatically infected rabbits showed levels corresponding to those reported for human patients with clinically silent HTLV-1 infections. Proviral load was comparably increased in 50% of experimentally infected rabbits that developed either spontaneous benign or malignant tumors while infected. Similarly elevated provirus was found in organs of rabbits with experimentally induced acute leukemia/lymphoma-like disease. Levels of provirus in organs taken at necropsy varied widely suggesting that reservoirs of infections exist in non-lymphoid organs not traditionally thought to be targets for HTLV-1. Conclusion Proviral load measurement is a valuable enhancement to the rabbit model for HTLV-1 infection providing a metric to monitor clinical status of the infected animals as well as a means for the testing of treatment to combat infection. In some cases proviral load in blood did not reflect organ proviral levels, revealing a limitation of this method for monitoring health status of HTLV-1 infected individuals.

Establishment of a new model for culturing rabbit osteoblasts in vitro

International Nuclear Information System (INIS)

Cao Xianying; Yin Meizhen; Zhang Lina; Li Shipu; Cao Yang

2006-01-01

To establish an experimental model for culturing rabbit osteoblasts in vitro, the osteoblasts were isolated from the calvarial bone of a 15-day old rabbit using a method of culturing the bone pieces in a medium after they had been digested by an enzyme for 15 min. The acquired cells were assayed by cell morphology, alkaline phosphatase activity and production of a mineralized matrix. The results showed that the cells had the morphologic characteristics and some biological behaviours of osteoblasts. Based on the primary isolation of osteoblasts from bone and combining digestion with explants, a novel model for culturing rabbit osteoblasts in vitro was established, which is easy, efficient and effective. This model can be used in many studies of osteogenesis mechanisms and bone replacement materials. (communication)

Detection of hepatic VX2 tumors in rabbits: comparison of conventional US and phase- inversion harmonic US during the liver- specific late phase of contrast enhancement

International Nuclear Information System (INIS)

Lee, Jeong Min; Youk, Ji Hyun; Lee, Young Hwan; Kim, Young Kon; Kim, Chong Soo; Li, Chun Ai

2003-01-01

To compare phase-inversion sonography during the liver-specific phase of contrast enhancement using a microbubble contrast agent with conventional B-mode sonography for the detection of VX2 liver tumors. Twenty-three rabbits, 18 of which had VX2 liver tumor implants, received a bolus injection of 0.6 g of Levovist (200 mg/ml). During the liver-specific phase of this agent, they were evaluated using both conventional sonography and contrast-enhanced phase-inversion harmonic imaging (CEPIHI). Following sacrifice of the animals, pathologic analysis was performed and the reference standard thus obtained. The conspicuity, size and number of the tumors before and after contrast administration, as determined by a sonographer, were compared between the two modes and with the pathologic findings. CE-PIHI demonstrated marked hepatic parenchymal enhancement in all rabbits. For VX2 tumors detected at both conventional US and CE- PIHI, conspicuity was improved by contrast-enhanced PIHI. On examination of gross specimens, 52 VX2 tumors were identified. Conventional US correctly detected 18 of the 52 (34.6%), while PIHI detected 35 (67.3%) (p < 0.05). In particular, conventional US detected only three (8.3%) of the 36 tumors less than 10 mm in diameter, but CE-PIHI detected 19 such tumors (52.8%) (p < 0.05). Compared to conventional sonography, PIHI performed during the liver-specific phase after intravenous injection of Levovist is markedly better at detecting VX2 liver tumors

The rabbit as an experimental model in laryngology

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Carneiro, Christiano de Giacomo

2009-06-01

Full Text Available Introduction: In the research in laryngology we normally use animal models. The animal experimentation may also contribute largely for this evolution, mainly for the easy access compared to human larynxes and for they are more easily controlled. Objective: The objective of this work is to analyze the laryngofissure with vocal cords graft as an experimental surgical technique in male adult rabbits. Method: We studied 46 New Zealand albino rabbits submitted to microsurgery in both vocal cords with autologous unilateral or bilateral graft of fat or fascia. Results: There were 4 losses of 3 animals until the first week of the postoperative period and another after 19 days after surgery. In the subsequent animals there were no infection, hematoma or sutures dehiscence. Conclusion: The study enables the conclusion that the experimental laryngofissure in rabbits is a safe method that may be used for laryngological studies.

Experimental model of cutaneous radiation injury in rabbits

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Meirelles, Rafael Panisi de Campos [Universidade Federal de Sao Paulo (EPM/UNIFESP), SP (Brazil). Escola Paulista de Medicina; Hochman, Bernardo [Universidade Federal de Sao Paulo (EPM/UNIFESP), SP (Brazil). Escola Paulista de Medicina. Dept. de Cirurgia; Helene Junior, Americo; Fraga, Murillo Francisco Pires [Faculdade de Ciencias Medicas da Santa Casa de Sao Paulo (FCMSCSP), SP (Brazil). Dept. de Cirurgia. Divisao de Cirurgia Plastica; Lellis, Rute [Faculdade de Ciencias Medicas da Santa Casa de Sao Paulo (FCMSCSP), SP (Brazil). Divisao de Patologia; Ferreira, Lydia Masako, E-mail: rpcmeirelles@yahoo.com.br, E-mail: lydia.dcir@epm.br [Universidade Federal de Sao Paulo (EPM/UNIFESP), SP (Brazil). Escola Paulista de Mediciana. Divisao de Cirugia Plastica

2013-07-01

Purpose: to describe an experimental model of cutaneous radiation injury in rabbits. Methods: on this study eight six-month-old New Zealand male rabbits, with an average weight of 2.5kg were used. They were distributed in four groups (n=2 per group). The control group did not receive radiotherapy and the others received one radiotherapy session of 2000, 3000 and 4500 cGy, respectively. Photographic analysis and histopathological evaluation of the irradiated areas were carried out. Results: after 30 days, the animals from the control group had all their hair grown. In spite of that, the animals from group 2000 cGy had a 60-day alopecia and from group 3000 cGy, a 90-day alopecia. After the 30th day, the 3000cGy group demonstrated 90-day cutaneous radiation injuries, graded 3 and 4. One of the animals from group 4500 cGy died on the 7th day with visceral necrosis. The other from the same group had total skin necrosis. A progressive reduction of glands and blood vessels count and an increase on collagen deposition was observed. Conclusion: The proposed experimental model is reproducible. This study suggests that the dosage 4500cGy is excessive and the 3000 cGy is the most effective for this experimental model of cutaneous radiation injury in rabbits. (author)

Effect of nano-silver hydrogel coating film on deep partial thickness scald model of rabbit.

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Xi, Peng; Li, Yan; Ge, Xiaojin; Liu, Dandan; Miao, Mingsan

2018-05-01

Observing the effect of nano-silver hydrogel coating film on deep partial thickness scald model of rabbit. We prepared boiling water scalded rabbits with deep II degree scald models and applied high, medium and low doses of nano-silver hydrogel coating film for different time and area. Then we compared the difference of burned paper weight before administration and after administration model burns, burn local skin irritation points infection, skin crusting and scabs from the time, and the impact of local skin tissue morphology. Rabbits deep II degree burn model successful modeling; on day 12, 18, high, medium and low doses of nano-silver hydrogel coating film significantly reduced skin irritation of rabbits infected with the integral value ( P  film group significantly decreased skin irritation, infection integral value ( P  film significantly reduced film rabbits' scalded skin crusting time ( P  film on the deep partial thickness burns has a significant therapeutic effect; external use has a significant role in wound healing.

Cavitation-enhanced MR-guided focused ultrasound ablation of rabbit tumors in vivo using phase shift nanoemulsions

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Kopechek, Jonathan A.; Park, Eun-Joo; Zhang, Yong-Zhi; Vykhodtseva, Natalia I.; McDannold, Nathan J.; Porter, Tyrone M.

2014-07-01

Advanced tumors are often inoperable due to their size and proximity to critical vascular structures. High intensity focused ultrasound (HIFU) has been developed to non-invasively thermally ablate inoperable solid tumors. However, the clinical feasibility of HIFU ablation therapy has been limited by the long treatment times (on the order of hours) and high acoustic intensities required. Studies have shown that inertial cavitation can enhance HIFU-mediated heating by generating broadband acoustic emissions that increase tissue absorption and accelerate HIFU-induced heating. Unfortunately, initiating inertial cavitation in tumors requires high intensities and can be unpredictable. To address this need, phase-shift nanoemulsions (PSNE) have been developed. PSNE consist of lipid-coated liquid perfluorocarbon droplets that are less than 200 nm in diameter, thereby allowing passive accumulation in tumors through leaky tumor vasculature. PSNE can be vaporized into microbubbles in tumors in order to nucleate cavitation activity and enhance HIFU-mediated heating. In this study, MR-guided HIFU treatments were performed on intramuscular rabbit VX2 tumors in vivo to assess the effect of vaporized PSNE on acoustic cavitation and HIFU-mediated heating. HIFU pulses were delivered for 30 s using a 1.5 MHz, MR-compatible transducer, and cavitation emissions were recorded with a 650 kHz ring hydrophone while temperature was monitored using MR thermometry. Cavitation emissions were significantly higher (P cavitation which correlates with enhanced HIFU-mediated heating in tumors. This suggests that PSNE could potentially be used to reduce the time and/or acoustic intensity required for HIFU-mediated heating, thereby increasing the feasibility and clinical efficacy of HIFU thermal ablation therapy.

Hierarchical spatial models for predicting pygmy rabbit distribution and relative abundance

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Wilson, T.L.; Odei, J.B.; Hooten, M.B.; Edwards, T.C.

2010-01-01

Conservationists routinely use species distribution models to plan conservation, restoration and development actions, while ecologists use them to infer process from pattern. These models tend to work well for common or easily observable species, but are of limited utility for rare and cryptic species. This may be because honest accounting of known observation bias and spatial autocorrelation are rarely included, thereby limiting statistical inference of resulting distribution maps. We specified and implemented a spatially explicit Bayesian hierarchical model for a cryptic mammal species (pygmy rabbit Brachylagus idahoensis). Our approach used two levels of indirect sign that are naturally hierarchical (burrows and faecal pellets) to build a model that allows for inference on regression coefficients as well as spatially explicit model parameters. We also produced maps of rabbit distribution (occupied burrows) and relative abundance (number of burrows expected to be occupied by pygmy rabbits). The model demonstrated statistically rigorous spatial prediction by including spatial autocorrelation and measurement uncertainty. We demonstrated flexibility of our modelling framework by depicting probabilistic distribution predictions using different assumptions of pygmy rabbit habitat requirements. Spatial representations of the variance of posterior predictive distributions were obtained to evaluate heterogeneity in model fit across the spatial domain. Leave-one-out cross-validation was conducted to evaluate the overall model fit. Synthesis and applications. Our method draws on the strengths of previous work, thereby bridging and extending two active areas of ecological research: species distribution models and multi-state occupancy modelling. Our framework can be extended to encompass both larger extents and other species for which direct estimation of abundance is difficult. ?? 2010 The Authors. Journal compilation ?? 2010 British Ecological Society.

Modeling Rabbit Responses to Single and Multiple Aerosol ...

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Journal Article Survival models are developed here to predict response and time-to-response for mortality in rabbits following exposures to single or multiple aerosol doses of Bacillus anthracis spores. Hazard function models were developed for a multiple dose dataset to predict the probability of death through specifying dose-response functions and the time between exposure and the time-to-death (TTD). Among the models developed, the best-fitting survival model (baseline model) has an exponential dose-response model with a Weibull TTD distribution. Alternative models assessed employ different underlying dose-response functions and use the assumption that, in a multiple dose scenario, earlier doses affect the hazard functions of each subsequent dose. In addition, published mechanistic models are analyzed and compared with models developed in this paper. None of the alternative models that were assessed provided a statistically significant improvement in fit over the baseline model. The general approach utilizes simple empirical data analysis to develop parsimonious models with limited reliance on mechanistic assumptions. The baseline model predicts TTDs consistent with reported results from three independent high-dose rabbit datasets. More accurate survival models depend upon future development of dose-response datasets specifically designed to assess potential multiple dose effects on response and time-to-response. The process used in this paper to dev

Effect of hepatic blood flow alteration on the therapeutic effect of cryoablation in VX2 hepatic tumor rabbit: an experimental study

International Nuclear Information System (INIS)

Guo Zhi; Ni Hong; Li Baoguo; Hu Yonghua; Xing Wenge; Liu Fang

2008-01-01

Objective: To investigate the effect of alteration of blood flow in the hepatic artery on the therapeutic effect of cryoablation in VX2 hepatic tumor rabbit model. Methods: Thirty rabbits with VX2 hepatic tumor were divided into three groups according to hepatic artery blood flow: complete occlusion of the hepatic artery(group A), partial occlusion of the hepatic artery (group B), and no occlusion of the hepatic artery (group C). With conventional CT scan and perfusion scan, the values of blood flow (BF) and blood volume(BV) of VX 2 tumor were computed and the differences among the three groups were analyzed. After cryoablation, the animals were euthanized and the livers were removed. The hepatic tissue from the cryoablation area and surrounding area underwent both methyl thiazolyl tetrazolium (MTY) diaphorase staining and triphenyl tetrazolium chloride (TTC) staining. The gross pathology and histopathological changes were observed. Results: (1)The BF and BV in the three groups were: (7.23 + 2. 15 ) ml·100 g -1 ·min -1 and (1.63±0.52) ml/100 g in group A; (32.65±6.12) ml·100 g -1 ·min -1 and (9.32±2.63) ml/100 g in group B; (61.34±12.15) ml·100 g -1 ·min -1 and (17.51± 3.14) ml/100 g in group C, respectively. There were significant differences among the three groups in the BF and BV (F value was 452.16 and 421.33 in the BF and BV, respectively, P <0.01); (2) The maximum diameter of cryoablation-induced necrosis was (2.3±0.3)cm in group A, (1.5±0.2) cm in group B, and (0.8±0.1) cm in group C, respectively. The difference was significant among the groups (F value was 315.32,P <0.01). (3) There were well-defined frozen areas, bordering areas and normal surrounding areas in MTT staining. In group C, positive staining around some blood vessels could be seen. Conclusion: Alteration of the blood flow in the hepatic artery can affect the cryoablation efficacy. With the decrease of hepatic artery blood flow, the efficacy of cryoablation on liver tumor

Tc-99m annexin V imaging and apoptosis staining in rabbit model of osteoarthritis

International Nuclear Information System (INIS)

Kang, Do Young; Jeong, Young Jin; Choi, Sun Mee; Lee, Sung Won; Chung, Won Tae; Yoo, Young Hyun

2004-01-01

Recent studies showed that, in osteoarthritis (OA), articular chondrocytes appeared to be eliminated by apoptosis. Tc-99mm Annexin V has been successfully used for non-invasive gamma imaging of apoptosis in tumor. myocardial infarction and transplantation. We studied Tc-99m Annexin V imaging and apoptosis staining in rabbit model of osteoarthritis. Osteoarthritis was induced in rabbits by intra-articular injection of 1.0 mg collagenase and surgical transection of leg ligament. Animals were dissected at 2, 4, 6 and 8 weeks after the initiation of the injections. For histological observation, the paraffin sections were stained with hematoxylin and eosin. To confirm that osteoarthritis was induced, immunohistochemistry to TRAIL was conducted on the sections and TRAIL positive cells was revealed by DAB. Tc-99m Annexin V was injected 16 ug/1 mCi/kg and regional images were acquired 10 and 60 min postinjection. A few days later Tc-99m MDP imaging was also acquired. Two weeks after injection, the surface layer of cartilage was lost, chondrocytes in the transitional zone have disappeared, and cleft in the transitional zone were shown. Four weeks after injection, moderate cell cloning in transitional and radial zone was appeared. Six weeks after injection, cell cloning was more apparent in the transitional and radial zones. Whereas TRAIL positive cells were not found in the chondrocytes from the control cartilage, most chondrocytes from the collagenase injected cartilage were TRAIL-positive. Tc-99m Annexin V imaging showed increase uptake in knee area of injuried side to normal side. And Tc-99m MDP imaging also had same findings. In rabbit model of osteoarthritis, apoptosis was detected by Tc-99m Annexin V imaging noninvasively and it was correlated by pathologic staining for apoptosis

Effects of GGCX overexpression on anterior cruciate ligament transection-induced osteoarthritis in rabbits.

Science.gov (United States)

Fu, Xiaoling; Qiu, Ruiyun; Tang, Chunfang; Wang, Xiaomei; Cheng, Xigao; Yin, Ming

2018-03-01

Effective therapeutic methods for osteoarthritis (OA) are lacking. γ‑glutamyl carboxylase (GGCX) is a key enzyme that regulates carboxylation of cartilage matrix Gla protein (MGP). Whether GGCX overexpression protects against OA remains unknown. The aim of the present study was to explore the effects of GGCX overexpression on anterior cruciate ligament transection (ACLT)‑induced OA and its mechanisms in Japanese white rabbits. ACLT surgery was used to establish an OA model in rabbits. A total of 48 rabbits were randomly divided into 4 groups: Sham, OA model + GGCX overexpression plasmid, OA model + saline and OA model + empty vector. The expression of uncarboxylated MGP (ucMGP), carboxylated MGP (cMGP), matrix metalloproteinase (MMP)‑13, collagen type X, collagen type II, tumor necrosis factor (TNF)‑α and interleukin (IL)‑1β were detected by ELISA, immunohistochemistry, reverse transcription‑quantitative polymerase chain reaction and western blotting. Morphological changes to tibial cartilage were assessed by Giemsa and safranin O‑fast green staining, respectively. Compared with the Sham control, GGCX expression was significantly decreased in the OA Model group. GGCX expression was increased by injection of a lentivirus‑carried overexpression plasmid that encoded GGCX. GGCX overexpression ameliorated ATLC‑induced damage in articular cartilage. OA Model rabbits exhibited significantly decreased expression levels of cMGP and collagen type II, and increased expression of ucMGP, collagen type X, MMP‑13, IL‑1β and TNF‑α. Notably, these expression levels were reversed by GGCX overexpression in OA Model rabbits. Results from the present study indicated that GGCX expression was decreased in OA Model rabbits, whereas overexpression of GGCX was able to promote carboxylation of MGP, reduce inflammation, decrease MMP‑13 expression and regulate collagen expression. The results also indicated that GGCX may serve as a therapeutic target for OA.

Effect of nano-silver hydrogel coating film on deep partial thickness scald model of rabbit

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Peng Xi

2018-05-01

Full Text Available Objective: Observing the effect of nano-silver hydrogel coating film on deep partial thickness scald model of rabbit. Method: We prepared boiling water scalded rabbits with deep II degree scald models and applied high, medium and low doses of nano-silver hydrogel coating film for different time and area. Then we compared the difference of burned paper weight before administration and after administration model burns, burn local skin irritation points infection, skin crusting and scabs from the time, and the impact of local skin tissue morphology. Result: Rabbits deep II degree burn model successful modeling; on day 12, 18, high, medium and low doses of nano-silver hydrogel coating film significantly reduced skin irritation of rabbits infected with the integral value (P < 0.01, P < 0.05; high, medium and low doses of nano-silver hydrogel coating film group significantly decreased skin irritation, infection integral value (P < 0.01, P < 0.05; high, medium and low doses of nano-silver hydrogel coating film significantly reduced film rabbits’ scalded skin crusting time (P < 0.01, significantly shortened the rabbit skin burns from the scab time (P < 0.01, and significantly improved the treatment of skin diseases in rabbits scald model change (P < 0.01, P < 0.05. Conclusion: The nano-silver hydrogel coating film on the deep partial thickness burns has a significant therapeutic effect; external use has a significant role in wound healing. Keywords: Nano-silver hydrogel coating film, Deep degree burns, Topical, Rabbits

Studies on uptake and distribution of chemotherapeutic agents to malignant tumors of the head and neck in rabbits, 2

International Nuclear Information System (INIS)

Yamada, Ryuichi

1981-01-01

Experiments were performed to investigate incorporation and distribution of chemotherapeutic agents into malignant tumors of the head and neck by microautoradiographic and electron microscopic-autoradiographic observations of VX2 carcinoma transplanted in the lower genial region of rabbits after injection of 3 H-Adriamycin as a tracer. The following findings were obtained. 1. On microautoradiograms, 3 H-Adriamycin was distributed predominantly in the nucleoplasm, rather than in the cytoplasm, of tumor tissues. 2. At the ultrastructural level, 3 H-Adriamycin was localized in the nuclear membrane and nucleoli within the nucleoplasm and in the rough endoplasmic reticulum and secretory granules within the cytoplasm. 3. These findings seem to indicate that Adriamycin may inhibit the synthesis of DNA and RNA in the nucleoplasm. (author)

Effects of morphine on the expression of cytokines and inflammatory mediators in a rabbit model of endotoxin-induced experimental uveitis

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Kethye P. Ortencio

2015-12-01

Full Text Available ABSTRACT Purpose: To evaluate the effects of 1% morphine instillation on clinical parameters, aqueous humor turbidity, and expression levels of tumor necrosis factor alpha (TNF-α, interleukin-1 beta (IL-1beta, prostaglandin E2 (PGE2, and myeloperoxidase (MPO in rabbits with endotoxin-induced experimental uveitis. Methods: Twenty four New Zealand white rabbits were divided into four groups (n=6 each: control (CG, morphine (MG, naloxone (NG, and morphine-naloxone (MNG groups. Under dissociative anesthesia, 0.1 mL of solution containing 0.2 µg of lipopolysaccharide (LPS endotoxin from the Salmonella typhimurium cell wall was injected in the vitreous chamber. Clinical evaluations (conjunctical hyperemia, chemosis blepharospasm, and ocular discharge and laser flaremetry were performed before (baseline, and 10 and 20 hours after induction of uveitis. Rabbits were subsequently euthanized and eyes were enucleated to quantify expression levels of TNF-α, IL-1 beta, PGE2, and MPO. Results: No significant differences in clinical parameters and flare values were observed between the study groups. TNF-α and IL-1 beta levels increased significantly in the CG, MG, NG, and MNG groups compared to baseline (P0.05. Conclusions: Morphine has no effect on clinical parameters, flare, or expression levels of inflammatory mediators in a rabbit model of uveitis induced by intravitreal injection of LPS.

MR and pathologic correlation of rabbit VX-2 carconoma

International Nuclear Information System (INIS)

Kang, H.S.; Kim, S.M.; Im, J.G.; Kim, C.W.; Han, M.C.

1991-01-01

This paper evaluates the reliability of MR imaging in tissue characterization and depiction of tumor boundaries. The authors performed MR-pathologic correlation using parosteally implanted VX-2 carcinoma in 17 rabbit thighs. T1-weighted, T2-weighted, and Gd-DTPA-enhanced T1-weighted axial images were obtained 10-20 days after tumor implantation. After the animals were killed, freezing, sectioning along the MR imaging planes, and histopathologic examination were done. For accurate MR-pathologic correlation, rabbits were fixed on the cardboard plate to minimize position change during the procedures. Tumor boundaries depicted on MR images were larger than those depicted on the specimen. Small tumors were surrounded by capsule-like, hypervascular (mainly lymphatics), loose connective tissue. Loose connective tissue became compact with tumor growth. This connective tissue showed high signal intensity on both T2-weighted and Gd-DTPA-enhanced T1-weighted images. Muscle atrophy with development of lymphatics around the tumor also contributed high signal intensity on MR images. Peritumoral edema and inflammatory reaction were not remarkable. Peritumoral lymphatics, rich connective tissue, and muscle atrophy exaggerated the size of experimentally induced malignant musculoskeletal tumors on MR images

Sinus Microanatomy and Microbiota in a Rabbit Model of Rhinosinusitis

Science.gov (United States)

Cho, Do-Yeon; Mackey, Calvin; Van Der Pol, William J.; Skinner, Daniel; Morrow, Casey D.; Schoeb, Trenton R.; Rowe, Steven M.; Swords, William E.; Tearney, Guillermo J.; Woodworth, Bradford A.

2018-01-01

Background: Rabbits are useful for preclinical studies of sinusitis because of similar physiologic features to humans. The objective of this study is to develop a rabbit model of sinusitis that permits assessment of microanatomy and sampling for evaluating shifts in the sinus microbiota during the development of sinusitis and to test how the mucociliary clearance (MCC) defect might lead to dysbiosis and chronic rhinosinusitis (CRS). Methods: Generation of CRS was accomplished with an insertion of a sterile sponge into the left middle meatus of New Zealand white rabbits (n = 9) for 2 weeks. After sponge removal, 4 rabbits were observed for another 10 weeks and evaluated for CRS using endoscopy, microCT, visualization of the functional micro-anatomy by micro-optical coherence tomography (μOCT), and histopathological analysis of the sinus mucosa. Samples were taken from the left middle meatus and submitted for microbiome analysis. Results: CT demonstrated opacification of all left sinuses at 2 weeks in all rabbits (n = 9), which persisted in animals followed for another 12 weeks (n = 4). Histology at week 2 showed mostly neutrophils. On week 14, significant infiltration of plasma cells and lymphocytes was noted with increased submucosal glands compared to controls (p = 0.02). Functional microanatomy at 2 weeks showed diminished periciliary layer (PCL) depth (p < 0.0001) and mucus transport (p = 0.0044) compared to controls despite a thick mucus layer. By 12 weeks, the thickened mucus layer was resolved but PCL depletion persisted in addition to decreased ciliary beat frequency (CBF; p < 0.0001). The mucin fermenting microbes (Lactobacillales, Bacteroidales) dominated on week 2 and there was a significant shift to potential pathogens (e.g., Pseudomonas, Burkholderia) by week 14 compared to both controls and the acute phase (p < 0.05). Conclusion: We anticipate this reproducible model will provide a means for identifying underlying mechanisms of airway-surface liquid

Sinus Microanatomy and Microbiota in a Rabbit Model of Rhinosinusitis

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Do-Yeon Cho

2018-01-01

Full Text Available Background: Rabbits are useful for preclinical studies of sinusitis because of similar physiologic features to humans. The objective of this study is to develop a rabbit model of sinusitis that permits assessment of microanatomy and sampling for evaluating shifts in the sinus microbiota during the development of sinusitis and to test how the mucociliary clearance (MCC defect might lead to dysbiosis and chronic rhinosinusitis (CRS.Methods: Generation of CRS was accomplished with an insertion of a sterile sponge into the left middle meatus of New Zealand white rabbits (n = 9 for 2 weeks. After sponge removal, 4 rabbits were observed for another 10 weeks and evaluated for CRS using endoscopy, microCT, visualization of the functional micro-anatomy by micro-optical coherence tomography (μOCT, and histopathological analysis of the sinus mucosa. Samples were taken from the left middle meatus and submitted for microbiome analysis.Results: CT demonstrated opacification of all left sinuses at 2 weeks in all rabbits (n = 9, which persisted in animals followed for another 12 weeks (n = 4. Histology at week 2 showed mostly neutrophils. On week 14, significant infiltration of plasma cells and lymphocytes was noted with increased submucosal glands compared to controls (p = 0.02. Functional microanatomy at 2 weeks showed diminished periciliary layer (PCL depth (p < 0.0001 and mucus transport (p = 0.0044 compared to controls despite a thick mucus layer. By 12 weeks, the thickened mucus layer was resolved but PCL depletion persisted in addition to decreased ciliary beat frequency (CBF; p < 0.0001. The mucin fermenting microbes (Lactobacillales, Bacteroidales dominated on week 2 and there was a significant shift to potential pathogens (e.g., Pseudomonas, Burkholderia by week 14 compared to both controls and the acute phase (p < 0.05.Conclusion: We anticipate this reproducible model will provide a means for identifying underlying mechanisms of airway

Implementation of the ISTH classification of non-overt DIC in a thromboplastin induced rabbit model

DEFF Research Database (Denmark)

Berthelsen, Line Olrik; Kristensen, Annemarie Thuri; Wiinberg, Bo

2009-01-01

, but the scoring systems have rarely been applied to animal models of DIC. In this study, we use rabbit brain thromboplastin (thromboplastin) to induce DIC in a rabbit model and test the applicability of the ISTH criteria for standardized diagnosis of DIC. Cardiovascular and haematological parameters from rabbits......, either saline-injected or administered 0.625, 1.25, 2.5 or 5 mg thromboplastin/kg as a single bolus, were collected at four timepoints over a 90 minute period. All groups of rabbits were scored at each time point according to the ISTH diagnostic criteria for non-overt DIC. Injection of 5 mg...... and number of thrombi in lung vasculature was seen. The administration of a bolus of 1.25 - 2.5 mg thromboplastin/kg to rabbits induced a reproducible dose dependent model of non-overt DIC according to the ISTH diagnostic criteria. We conclude that the non-overt ISTH score can be applied to evaluate severity...

Modelling landscape-level numerical responses of predators to prey: the case of cats and rabbits.

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Jennyffer Cruz

Full Text Available Predator-prey systems can extend over large geographical areas but empirical modelling of predator-prey dynamics has been largely limited to localised scales. This is due partly to difficulties in estimating predator and prey abundances over large areas. Collection of data at suitably large scales has been a major problem in previous studies of European rabbits (Oryctolagus cuniculus and their predators. This applies in Western Europe, where conserving rabbits and predators such as Iberian lynx (Lynx pardinus is important, and in other parts of the world where rabbits are an invasive species supporting populations of introduced, and sometimes native, predators. In pastoral regions of New Zealand, rabbits are the primary prey of feral cats (Felis catus that threaten native fauna. We estimate the seasonal numerical response of cats to fluctuations in rabbit numbers in grassland-shrubland habitat across the Otago and Mackenzie regions of the South Island of New Zealand. We use spotlight counts over 1645 km of transects to estimate rabbit and cat abundances with a novel modelling approach that accounts simultaneously for environmental stochasticity, density dependence and varying detection probability. Our model suggests that cat abundance is related consistently to rabbit abundance in spring and summer, possibly through increased rabbit numbers improving the fecundity and juvenile survival of cats. Maintaining rabbits at low abundance should therefore suppress cat numbers, relieving predation pressure on native prey. Our approach provided estimates of the abundance of cats and rabbits over a large geographical area. This was made possible by repeated sampling within each season, which allows estimation of detection probabilities. A similar approach could be applied to predator-prey systems elsewhere, and could be adapted to any method of direct observation in which there is no double-counting of individuals. Reliable estimates of numerical

Radiation-induced heart disease due to intrathonacic tumor radiotherapy of a single dose to the rabbits' heart

International Nuclear Information System (INIS)

Zhou Weibing; Feng Yan; Chen Jiayi; Luo Quanyong

2007-01-01

found in rabbits heart irradiated in clinical related single dose ranging from 0 to 18 Gy, which suggests that the incidence of acute RIHD is lower in thoracic tumor radiotherapy. Yet, we must bear in mind, if the dose is more than or equal to 22 Gy, severe heart damage may occur. The dose to the heart should be kept minimum. ECG is an useful method to detect the RIHD. Further research on the validity of heart SPECT( 99 Tc m -MIBI) is necessary, and important. There are no positive findings of the 99 Tc m -HL91 and 99m Tc-Annexin V used as SPECT agents to test the RIHD. (authors)

The Antitumor Effect and Hepatotoxicity of a Hexokinase II Inhibitor 3-Bromopyruvate: In Vivo Investigation of Intraarterial Administration in a Rabbit VX2 Hepatoma Model

International Nuclear Information System (INIS)

Jae, Hwan Jun; Chung, Jin Wook; Park, Hee Sun; Lee, Min Jong; Lee, Ki Chang; Kim, Hyo Cheol; Yoon, Jung Hwan; Park, Jae Hyung; Chung, He Son

2009-01-01

The purpose of this study was to compare the antitumor effect and hepatotoxicity of an intraarterial delivery of low-dose and high-dose 3-bromopyruvate (3-BrPA) and those of a conventional Lipiodol-doxorubicin emulsion in a rabbit VX2 hepatoma model. This experiment was approved by the animal care committee at our institution. VX2 carcinoma was implanted in the livers of 36 rabbits. Transcatheter intraarterial administration was performed using low dose 3- BrPA (25 mL in a 1 mM concentration, n = 10), high dose 3-BrPA (25 mL in a 5 mM concentration, n = 10) and Lipiodol-doxorubicin emulsion (1.6 mg doxorubicin/ 0.4 mL Lipiodol, n = 10), and six rabbits were treated with normal saline alone as a control group. One week later, the proportion of tumor necrosis was calculated based on histopathologic examination. The hepatotoxicity was evaluated by biochemical analysis. The differences between these groups were statistically assessed with using Mann-Whitney U tests and Kruskal-Wallis tests. The tumor necrosis rate was significantly higher in the high dose group (93% ± 7.6 [mean ± SD]) than that in the control group (48% ± 21.7) (p = 0.0002), but the tumor necrosis rate was not significantly higher in the low dose group (62% ± 20.0) (p = 0.2780). However, the tumor necrosis rate of the high dose group was significantly lower than that of the Lipiodol-doxorubicin treatment group (99% ± 2.7) (p = 0.0015). The hepatotoxicity observed in the 3-BrPA groups was comparable to that of the Lipiodol-doxorubicin group. Even though intraarterial delivery of 3-BrPA shows a dose-related antitumor effect, single session treatment seems to have limited efficacy when compared with the conventional method

The antitumor effect and hepatotoxicity of a hexokinase II inhibitor 3-bromopyruvate: in vivo investigation of intraarterial administration in a rabbit VX2 hepatoma model.

Science.gov (United States)

Jae, Hwan Jun; Chung, Jin Wook; Park, Hee Sun; Lee, Min Jong; Lee, Ki Chang; Kim, Hyo-Cheol; Yoon, Jung Hwan; Chung, Hesson; Park, Jae Hyung

2009-01-01

The purpose of this study was to compare the antitumor effect and hepatotoxicity of an intraarterial delivery of low-dose and high-dose 3-bromopyruvate (3-BrPA) and those of a conventional Lipiodol-doxorubicin emulsion in a rabbit VX2 hepatoma model. This experiment was approved by the animal care committee at our institution. VX2 carcinoma was implanted in the livers of 36 rabbits. Transcatheter intraarterial administration was performed using low dose 3-BrPA (25 mL in a 1 mM concentration, n = 10), high dose 3-BrPA (25 mL in a 5 mM concentration, n = 10) and Lipiodol-doxorubicin emulsion (1.6 mg doxorubicin/ 0.4 mL Lipiodol, n = 10), and six rabbits were treated with normal saline alone as a control group. One week later, the proportion of tumor necrosis was calculated based on histopathologic examination. The hepatotoxicity was evaluated by biochemical analysis. The differences between these groups were statistically assessed with using Mann-Whitney U tests and Kruskal-Wallis tests. The tumor necrosis rate was significantly higher in the high dose group (93% +/- 7.6 [mean +/- SD]) than that in the control group (48% +/- 21.7) (p = 0.0002), but the tumor necrosis rate was not significantly higher in the low dose group (62% +/- 20.0) (p = 0.2780). However, the tumor necrosis rate of the high dose group was significantly lower than that of the Lipiodol-doxorubicin treatment group (99% +/- 2.7) (p = 0.0015). The hepatotoxicity observed in the 3-BrPA groups was comparable to that of the Lipiodol-doxorubicin group. Even though intraarterial delivery of 3-BrPA shows a dose-related antitumor effect, single session treatment seems to have limited efficacy when compared with the conventional method.

The Antitumor Effect and Hepatotoxicity of a Hexokinase II Inhibitor 3-Bromopyruvate: In Vivo Investigation of Intraarterial Administration in a Rabbit VX2 Hepatoma Model

Energy Technology Data Exchange (ETDEWEB)

Jae, Hwan Jun; Chung, Jin Wook; Park, Hee Sun; Lee, Min Jong; Lee, Ki Chang; Kim, Hyo Cheol; Yoon, Jung Hwan; Park, Jae Hyung [Seoul National University Hospital, Seoul (Korea, Republic of); Chung, He Son [Korea Institute of Science and Technology, Seoul (Korea, Republic of)

2009-12-15

The purpose of this study was to compare the antitumor effect and hepatotoxicity of an intraarterial delivery of low-dose and high-dose 3-bromopyruvate (3-BrPA) and those of a conventional Lipiodol-doxorubicin emulsion in a rabbit VX2 hepatoma model. This experiment was approved by the animal care committee at our institution. VX2 carcinoma was implanted in the livers of 36 rabbits. Transcatheter intraarterial administration was performed using low dose 3- BrPA (25 mL in a 1 mM concentration, n = 10), high dose 3-BrPA (25 mL in a 5 mM concentration, n = 10) and Lipiodol-doxorubicin emulsion (1.6 mg doxorubicin/ 0.4 mL Lipiodol, n = 10), and six rabbits were treated with normal saline alone as a control group. One week later, the proportion of tumor necrosis was calculated based on histopathologic examination. The hepatotoxicity was evaluated by biochemical analysis. The differences between these groups were statistically assessed with using Mann-Whitney U tests and Kruskal-Wallis tests. The tumor necrosis rate was significantly higher in the high dose group (93% +- 7.6 [mean +- SD]) than that in the control group (48% +- 21.7) (p = 0.0002), but the tumor necrosis rate was not significantly higher in the low dose group (62% +- 20.0) (p = 0.2780). However, the tumor necrosis rate of the high dose group was significantly lower than that of the Lipiodol-doxorubicin treatment group (99% +- 2.7) (p = 0.0015). The hepatotoxicity observed in the 3-BrPA groups was comparable to that of the Lipiodol-doxorubicin group. Even though intraarterial delivery of 3-BrPA shows a dose-related antitumor effect, single session treatment seems to have limited efficacy when compared with the conventional method

3.0 T MR diffusion weighted imaging in the evaluation of radio-frequency ablation of the liver VX2 tumors

International Nuclear Information System (INIS)

Liu Yubao; Liang Changhong; Wang Qiushi; Xie Shufei; Yu Yuanxin; Liu Zaiyi; Zhang Zhonglin

2010-01-01

Objective: To evaluate 3.0 T MR DWI techniques in detecting the lesions of pre and post-radiofrequency ablation of the rabbit liver VX2 tumors. Methods: Twenty two New Zealand white rabbits were used in this experiment. Twenty tumor fragments were implanted into the livers of 20 rabbits respectively. Two normal rabbits were used as controls for radiofrequency ablation of the normal liver. 3. 0 T MR DWI was performed 14 to 21 days after tumor implantation (mean, 17 days) in the tumor-bearing animals. Radiofrequency ablation was performed in the 18 tumor-bearing animals and in the two healthy animals. 3.0 T MRI and DWI were performed 7 to 10 days after radiofrequency ablation (mean, 8 days). Pathology was obtained immediately after the completion of post radiofrequency ablation MR imaging. The MRI features and ADC values of pre- and post -radiofrequency ablation lesions in the livers with VX2 tumors and normal rabbits were analyzed and correlation was made with histopathologic findings. Analysis of variance repeated measures were performed in analyzing the differences among the ADC values of different tissues with the same b value. Results: All 20 rabbit liver models of VX2 tumors were constructed successfully. One rabbit died of anesthetic overdose, another one showed necrosis within the implanted tumor. All 18 untreated VX2 tumors had predominantly low or iso-signal intensity on T 1 WI and high signal intensity on T 2 WI. All 18 VX2 tumors and 2 normal rabbits were treated by radiofrequency ablation successfully. Lesions treated by Radiofrequency ablation displayed low signal intensity on T 1 WI, and high signal intensity on T 2 WI. Seven to 10 days after radiofrequency ablation, lesions varied from having low signal intensity to slightly increased signal intensity on T 1 WI, with areas of mixed (high, intermediate, and low) signal intensity. A peripheral rim of high signal intensity with varying thickness on T 2 WI correlated with granulation tissue, which

A new rabbit model of implant-related biofilm infection: development and evaluation

Science.gov (United States)

Chu, Cheng-Bing; Zeng, Hong; Shen, Ding-Xia; Wang, Hui; Wang, Ji-Fang; Cui, Fu-Zhai

2016-03-01

This study is to establish a rabbit model for human prosthetic joint infection and biofilm formation. Thirty-two healthy adult rabbits were randomly divided into four groups and implanted with stainless steel screws and ultra-high molecular weight polyethylene (UHMWPE) washers in the non-articular surface of the femoral lateral condyle of the right hind knees. The rabbit knee joints were inoculated with 1 mL saline containing 0, 102, 103, 104 CFU of Staphylococcus epidermidis ( S. epidermidis) isolated from the patient with total knee arthroplasty (TKA) infection, respectively. On the 14th postoperative day, the UHMWPE washers from the optimal 103 CFU group were further examined. The SEM examination showed a typical biofilm construction that circular S. epidermidis were embedded in a mucous-like matrix. In addition, the LCSM examination showed that the biofilm consisted of the polysaccharide stained bright green fluorescence and S. epidermidis radiating red fluorescence. Thus, we successfully create a rabbit model for prosthetic joint infection and biofilm formation, which should be valuable for biofilm studies.

[ESTABLISHMENT OF A NEW RADIUS DEFECT MODEL BASED ON ULNA ANATOMICAL MEASUREMENT IN RABBITS].

Science.gov (United States)

Liu, Hanjiang; Guo, Ying; Mei, Wei

2016-02-01

To introduce a new bone defect model based on the anatomical measurement of radius and ulna in rabbits for offering a standard model for further tissue engineering research. Fifteen healthy 4-month-old New Zealand rabbits were selected for anatomic measurement and radiological measurement of the radius and ulna. Another 30 healthy 4-month-old New Zealand rabbits were randomly divided into groups A, B, and C (n=10). The radius bone defect was created bilaterally in 3 groups. In group A, the periosteum and interosseous membranes were fully removed with jig-saw by approach between extensor carpi radialis muscle and musculus extensor digitorum. The periosteum and interosseous membranes were fully removed in group B, and only periosteum was removed in group C with electric-saw by approach between extensor carpi radialis muscle and flexor digitorum profundus based on anatomical analysis results of ulnar and radial measurement. The gross observation, X-ray, micro-CT three-dimensional reconstruction, bone mineral density (BMD), and bone mineral content (BMC) were observed and recorded at immediate and 15 weeks after operation. HE staining and Masson staining were performed to observe bone formation in the defect areas. Blood vessel injury (1 rabbit), tendon injury (2 rabbits), postoperative hematoma (1 rabbit), and infection (1 rabbit) occurred in group A, postoperative infection (1 rabbit) in group C, and no postoperative complications in group B; the complication rate of group A (50%) was significantly higher than that of groups B (0%) and C (10%) (P0.05). HE staining and Masson staining results showed bone formation in group A, with structure disturbance and sclerosis. New bone formed in groups B and C, cartilage cells were observed in the center of bone cells. The radius bone defect model established by approach between extensor carpi radialis muscle and flexor digitorum profundus is an ideal model because of better exposures, less intra-operative blood loss, less

Novel model for end-neuroma formation in the amputated rabbit forelimb

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Kuiken Todd A

2010-03-01

Full Text Available Abstract Background The forelimb amputee poses many reconstructive challenges in the clinical setting, and there is a paucity of established surgical models for study. To further elucidate the pathogenic process in amputation neuroma formation, we created a reproducible, well-tolerated rabbit forelimb amputation model. Methods Upon approval from the Institutional Animal Care and Use Committee, 5 New Zealand White rabbits underwent left forelimb amputation. During this initial surgery, the median, radial and ulnar nerves were transected 1.6-2.5 (mean 2.0 cm distal to the brachial plexus, transposed onto the anterior chest wall and preserved at length. Six weeks subsequent to the amputation, the distal 5 mm of each neuroma was excised, and the remaining stump underwent histomorphometric analysis. Results The nerve cross sectional areas increased by factors of 1.99, 3.17, and 2.59 in the median (p = 0.077, radial (p Conclusion Given that the surgical model appears well-tolerated by the rabbits and that patterns of morphologic change are consistent and reproducible, we are encouraged to further investigate the utility of this model in the pathogenesis of neuroma formation.

Cavitation-enhanced MR-guided focused ultrasound ablation of rabbit tumors in vivo using phase shift nanoemulsions

International Nuclear Information System (INIS)

Kopechek, Jonathan A; Porter, Tyrone M; Park, Eun-Joo; Zhang, Yong-Zhi; Vykhodtseva, Natalia I; McDannold, Nathan J

2014-01-01

Advanced tumors are often inoperable due to their size and proximity to critical vascular structures. High intensity focused ultrasound (HIFU) has been developed to non-invasively thermally ablate inoperable solid tumors. However, the clinical feasibility of HIFU ablation therapy has been limited by the long treatment times (on the order of hours) and high acoustic intensities required. Studies have shown that inertial cavitation can enhance HIFU-mediated heating by generating broadband acoustic emissions that increase tissue absorption and accelerate HIFU-induced heating. Unfortunately, initiating inertial cavitation in tumors requires high intensities and can be unpredictable. To address this need, phase-shift nanoemulsions (PSNE) have been developed. PSNE consist of lipid-coated liquid perfluorocarbon droplets that are less than 200 nm in diameter, thereby allowing passive accumulation in tumors through leaky tumor vasculature. PSNE can be vaporized into microbubbles in tumors in order to nucleate cavitation activity and enhance HIFU-mediated heating. In this study, MR-guided HIFU treatments were performed on intramuscular rabbit VX2 tumors in vivo to assess the effect of vaporized PSNE on acoustic cavitation and HIFU-mediated heating. HIFU pulses were delivered for 30 s using a 1.5 MHz, MR-compatible transducer, and cavitation emissions were recorded with a 650 kHz ring hydrophone while temperature was monitored using MR thermometry. Cavitation emissions were significantly higher (P < 0.05) after PSNE injection and this was well correlated with enhanced HIFU-mediated heating in tumors. The peak temperature rise induced by sonication was significantly higher (P < 0.05) after PSNE injection. For example, the mean per cent change in temperature achieved at 5.2 W of acoustic power was 46 ± 22% with PSNE injection. The results indicate that PSNE nucleates cavitation which correlates with enhanced HIFU-mediated heating in tumors. This suggests that PSNE could

ISSLS PRIZE IN BASIC SCIENCE 2018: Growth differentiation factor-6 attenuated pro-inflammatory molecular changes in the rabbit anular-puncture model and degenerated disc-induced pain generation in the rat xenograft radiculopathy model.

Science.gov (United States)

Miyazaki, Shingo; Diwan, Ashish D; Kato, Kenji; Cheng, Kevin; Bae, Won C; Sun, Yang; Yamada, Junichi; Muehleman, Carol; Lenz, Mary E; Inoue, Nozomu; Sah, Robert L; Kawakami, Mamoru; Masuda, Koichi

2018-04-01

To elucidate the effects of growth differentiation factor-6 (GDF6) on: (i) gene expression of inflammatory/pain-related molecules and structural integrity in the rabbit intervertebral disc (IVD) degeneration model, and (ii) sensory dysfunction and changes in pain-marker expression in dorsal nerve ganglia (DRGs) in the rat xenograft radiculopathy model. Forty-six adolescent rabbits received anular-puncture in two non-consecutive lumbar IVDs. Four weeks later, phosphate-buffered saline (PBS) or GDF6 (1, 10 or 100 µg) was injected into the nucleus pulposus (NP) of punctured discs and followed for 4 weeks for gene expression analysis and 12 weeks for structural analyses. For pain assessment, eight rabbits were sacrificed at 4 weeks post-injection and NP tissues of injected discs were transplanted onto L5 DRGs of 16 nude rats to examine mechanical allodynia. The rat DRGs were analyzed immunohistochemically. In GDF6-treated rabbit NPs, gene expressions of interleukin-6, tumor necrosis factor-α, vascular endothelial growth factor, prostaglandin-endoperoxide synthase 2, and nerve growth factor were significantly lower than those in the PBS group. GDF6 injections resulted in partial restoration of disc height and improvement of MRI disc degeneration grades with statistical significance in rabbit structural analyses. Allodynia induced by xenograft transplantation of rabbit degenerated NPs onto rat DRGs was significantly reduced by GDF6 injection. Staining intensities for ionized calcium-binding adaptor molecule-1 and calcitonin gene-related peptide in rat DRGs of the GDF6 group were significantly lower than those of the PBS group. GDF6 injection may change the pathological status of degenerative discs and attenuate degenerated IVD-induced pain.

Computational fluid dynamics modeling of Bacillus anthracis spore deposition in rabbit and human respiratory airways

Energy Technology Data Exchange (ETDEWEB)

Kabilan, S.; Suffield, S. R.; Recknagle, K. P.; Jacob, R. E.; Einstein, D. R.; Kuprat, A. P.; Carson, J. P.; Colby, S. M.; Saunders, J. H.; Hines, S. A.; Teeguarden, J. G.; Straub, T. M.; Moe, M.; Taft, S. C.; Corley, R. A.

2016-09-01

Three-dimensional computational fluid dynamics and Lagrangian particle deposition models were developed to compare the deposition of aerosolized Bacillus anthracis spores in the respiratory airways of a human with that of the rabbit, a species commonly used in the study of anthrax disease. The respiratory airway geometries for each species were derived respectively from computed tomography (CT) and µCT images. Both models encompassed airways that extended from the external nose to the lung with a total of 272 outlets in the human model and 2878 outlets in the rabbit model. All simulations of spore deposition were conducted under transient, inhalation–exhalation breathing conditions using average species-specific minute volumes. Two different exposure scenarios were modeled in the rabbit based upon experimental inhalation studies. For comparison, human simulations were conducted at the highest exposure concentration used during the rabbit experimental exposures. Results demonstrated that regional spore deposition patterns were sensitive to airway geometry and ventilation profiles. Due to the complex airway geometries in the rabbit nose, higher spore deposition efficiency was predicted in the nasal sinus compared to the human at the same air concentration of anthrax spores. In contrast, higher spore deposition was predicted in the lower conducting airways of the human compared to the rabbit lung due to differences in airway branching pattern. This information can be used to refine published and ongoing biokinetic models of inhalation anthrax spore exposures, which currently estimate deposited spore concentrations based solely upon exposure concentrations and inhaled doses that do not factor in species-specific anatomy and physiology for deposition.

Neuroprotective effect of curcumin on spinal cord in rabbit model with ischemia/reperfusion.

Science.gov (United States)

Liu, Zhi-Qiang; Xing, Shan-Shan; Zhang, Wei

2013-03-01

Ischemic/reperfusion (I/R) injury of the spinal cord is a serious complication that can result from thoracoabdominal aortic surgery. To investigate the neuroprotective effect of curcumin against I/R injury in a rabbit model. A total of 36 rabbits were randomly divided into three groups: sham, I/R, and curcumin-treated group. Rabbits were subject to 30-min aortic occlusion to induce transient spinal cord ischemia. Neurological function was observed after reperfusion and spinal cord segment (L3-L5) was collected for histopathological evaluation. Malondialdehyde (MDA) and total superoxide dismutase (SOD) activity were also assayed. Rabbits in I/R group were induced to paraplegia. While after 48-hour treatment, compared with I/R group, curcumin significantly improved neurological function, reduced cell apoptosis and MDA levels as well as increased SOD activity (P curcumin, at least in an animal model, can attenuate transient spinal cord ischemic injury potentially via reducing oxidative damage, which may provide a novel approach in the treatment of spinal cord ischemic injury.

Experimental treatment of the transplanted hepatoma in rabbit by hepatic arterial embolization using interleukin-2 dextran microsphere and iodized

International Nuclear Information System (INIS)

Zeng Xiaohua; Wang Songzhang; Jin Deqin; Tang Ying; Ding Jinya; Feng Gansheng

2006-01-01

Objective: To observe the degree of necrosis in the transplanted hepatic tumor and the changes in immunity of the rabbits after hepatic arterial embolization using interleukin-2 (IL-2) dextran microsphere and iodized oil. Methods: IL-2 dextran microsphere and iodized oil were infused into hepatic artery of 20 rabbits with transplanted hepatic tumor. Infusion of dextran microspheres and iodized oil were taken in another transplanted hepatic tumor group of rabbits as the control. The blood samples were acquired pre-and post-embolization to measure the changes of IL-2 and sIL-2R in both groups. The rabbits were killed one week after the performance to get tumor tissue for pathologic examination. The comparison between using IL-2 dextran microsphere and dextran microsphere was made through optic and electronic microscopy for pathologic analysis. Results: Obvious increase of IL-2 and apparent decrease of sIL-2R in blood were demonstrated after the performance. The transplanted tumors mass underwent complete necrosis with false membranous capsule formation. In controlled group, slight increase of IL-2 and slight decrease of sIL-2R in blood were shown with partial central necrosis without false membraneous capsule formation of the transplanted tumor. Conclusions: The afficacy of the group IL-2 dextran microsphere was superior to group of arterial infusion of dextran microsphere in outcoming with tumor necrosis and strengthening the immunity of the rabbits. (authors)

Establishment of atherosclerotic model and USPIO enhanced MRI techniques study in rabbits

International Nuclear Information System (INIS)

Li Yonggang; Zhu Mo; Dai Yinyu; Chen Jianhua; Guo Liang; Ni Jiankun

2010-01-01

Objective: To explore the methods of establishment of atherosclerotic model and USPIO enhanced MRI techniques in rabbits. Methods: Thirty New Zealand male rabbits were divided randomly into two groups: 20 animals in the experiment group, 10 animals in the control group. Animal model of atherosclerosis was induced with aortic balloon endothelial injury and high-fat diet feeding. There was no intervention with the rabbits in control group. MRI examination included plan scan, USPIO enhanced black-blood sequences and white-blood sequence. The features of the plaques was analyzed in the experimental group and the effection on the image quality of different coils, sequences and parameters and a statistical study was also analyzed. Results: Animal model of atherosclerosis was successfully made in 12 rabbits and most plaques located in the abdomen aorta. There were 86 plaques within the scanning scope among which 67 plaques were positive to the Prussian blue staining. The image quality of knee joint coil was better than that of other coils. Although there was no difference in the detection of numbers of AS plaques between USPIO enhanced black-blood sequences and white-blood sequence (P > 0.05), blackblood sequences was superior to white-blood sequence in the demonstration of the components of plaque. Conclusion: The method of aortic balloon endothelial injury and high-fat diet feeding can easily establish the AS model in rabbits with a shorter period and it may be used for controlling the location of the plaques. USPIO enhanced MRI sequences has high sensitivity in the detection of the AS plauqes and can reveal the component of AS plaques. The optimization of MRI techniques is very important in the improvement of the image quality and the detection of the plaques. (authors)

The rabbit as an animal model for post-natal vitreous matrix differentiation and degeneration

NARCIS (Netherlands)

Los, L. I.

2008-01-01

Purpose This study evaluates whether rabbits are a suitable animal model to study post-natal vitreous differentiation and degeneration. Methods Human and rabbit eyes of various ages were studied by complementary anatomical techniques, light microscopy, and transmission electron microscopy. Results

Establishment of a blunt impact-induced brain injury model in rabbits

OpenAIRE

LI Kui; CAO Yun-xing; YANG Yong-qiang; YIN Zhi-yong; ZHAO Hui; WANG Li-jun

2012-01-01

【Abstract】 Objective: To establish an animal model to replicate the blunt impact brain injury in forensic medicine. Methods: Twenty-four New Zealand white rabbits were randomly divided into control group (n=4), minor injury group (n=10) and severe injury group (n=10). Based on the BIM-Ⅱ Horizontal Bio-impact Machine, self-designed iron bar was used to produce blunt brain injury. Two rabbits from each injury group were randomly selected to monitor the change of in...

Rabbit Calvarial Defect Model for Customized 3D-Printed Bone Grafts.

Science.gov (United States)

Lee, Kang-Gon; Lee, Kang-Sik; Kang, Yu-Jeoung; Hwang, Jong-Hyun; Lee, Se-Hwan; Park, Sang-Hyug; Park, Yongdoo; Cho, Young-Sam; Lee, Bu-Kyu

2018-05-01

Bone graft materials are commonly used to regenerate various bone defects, but their application is often limited because of the complex defect shape in various clinical conditions. Hence, customized bone grafts using three-dimensional (3D) printing techniques have been developed. However, conventional simple bone defect models are limited for evaluating the benefits and manufacturing accuracy of 3D-printed customized bone grafts. Thus, the aim of the present study was to develop a complex-shaped bone defect model. We designed an 8-shaped bony defect that consists of two simple circles attached to the rabbit calvarium. To determine the critical-sized defect (CSD) of the 8-shaped defects, 5.6- and 7-mm-diameter trephine burs were tested, and the 7-mm-diameter bur could successfully create a CSD, which was easily reproducible on the rabbit calvarium. The rate of new bone formation was 28.65% ± 8.63% at 16 weeks following creation of the defect. To confirm its efficacy for clinical use, the 8-shaped defect was created on a rabbit calvarium and 3D computed tomography (CT) was performed. A stereolithography file was produced using the CT data, and a 3D-printed polycaprolactone graft was fabricated. Using our 8-shaped defect model, we were able to modify the tolerances of the bone graft and calvarial defect to fabricate a more precise bone graft. Customized characteristics of the bone graft were then used to improve the accuracy of the bone graft. In addition, we confirmed the fitting ability of the 3D-printed graft during implantation of the graft. Our 8-shaped defect model on the rabbit calvarium using a 7.0-mm trephine bur may be a useful CSD model for evaluating 3D-printed graft materials.

The model of pulmonary embolism caused by autologous thrombus in rabbits

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Yu-Jiao Ding

2017-05-01

Full Text Available Objective: To establish a model of pulmonary embolism in rabbits by using autologous thrombosis of rabbit ear vein, to study the method of establishing acute pulmonary embolism by using autologous thrombus and to explore the diagnostic value of oxygen partial pressure in acute pulmonary embolism. Methods: Twenty rabbits were randomly divided into normal group (n=5, 7 h group, 24h group, 1 week after model establishment Group. The arterial blood gas analysis was performed on the carotid arteries of rabbits at 7 h, 24 h and 1 W after modeling. Results: Normal group oxygen partial pressure (93.15 ± 2.26 mmHg, 7 h group oxygen partial pressure (81.98 ± 1.94 mmHg, 24 h group oxygen partial pressure (84.55 ± 2.18 mmHg, 1 W group oxygen partial pressure (92.66 ± 1.92 mmHg. Normal group oxygen partial pressure and 7 h group, 24 h group oxygen partial pressure, P value was less than 0.05 and less than 0.01, indicating that the difference was statistically significant. Normal group oxygen partial pressure and 1 week group oxygen partial pressure, P value greater than 0.05, indicating that the difference was not statistically significant. Conclusion: The oxygen partial pressure was reduced at 7 h after the establishment of the acute pulmonary embolism model and failed to return to normal within 24 h. After 1 week, the embolus began to dissolve, the respiratory and circulatory system was reestablished, and the oxygen partial pressure gradually Return to normal level. Indicating that there is a positive correlation between oxygen partial pressure and acute pulmonary embolism.

Experimental model of bladder instability in rabbits

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Balasteghin K.T.

2003-01-01

Full Text Available OBJECTIVE: Propose a new experimental model of bladder instability in rabbits after partial bladder obstruction. MATERIALS AND METHODS: Thirty North Folk male rabbits, weighting 1,700 to 2,820 g (mean: 2,162 g were studied. The animals were distributed in 2 experimental groups, formed by 15 rabbits each: Group 1 - clinical control. In this group there was no surgical intervention; Group 2 - bladder outlet obstruction. In this group, after anesthetizing the animal, urethral cannulation with Foley catheter 10F was performed and then an adjustable plastic bracelet was passed around the bladder neck. It was then adjusted in order to not constrict the urethra. The following parameters were studied in M1 - pre-operative period; M2 - 4 weeks post-operatively moments: 1- urine culture; 2- cystometric study; 3- serum creatinine and BUN. RESULTS: Bladder weight was 2.5 times larger in the group with obstruction than in the control group. Cystometric evaluation showed a significant increase in maximal vesical volume in the final moment at Group G2. However, there was no statistically significant difference among the groups studied. There was no statistically significant difference between maximal detrusor pressure and vesical compliance in the different moments or in the studied groups. There was an absence of uninhibited detrusor contractions in all the animals in group 1, and involuntary contractions were detected in 93% of group 2 animals. There was no significant variation in BUN and serum creatinine either among the groups or in the same group. CONCLUSIONS: We observed in the group with obstruction a bladder weight 2.5 higher than normal bladders. We detected involuntary contractions in 93% of the animals in group 2, establishing this experimental model as appropriate to secondary bladder instability and partial bladder outlet obstruction.

Ultrasound guided double injection of blood into cisterna magna: a rabbit model for treatment of cerebral vasospasm.

Science.gov (United States)

Chen, Yongchao; Zhu, Youzhi; Zhang, Yu; Zhang, Zixuan; Lian, Juan; Luo, Fucheng; Deng, Xuefei; Wong, Kelvin K L

2016-02-06

Double injection of blood into cisterna magna using a rabbit model results in cerebral vasospasm. An unacceptably high mortality rate tends to limit the application of model. Ultrasound guided puncture can provide real-time imaging guidance for operation. The aim of this paper is to establish a safe and effective rabbit model of cerebral vasospasm after subarachnoid hemorrhage with the assistance of ultrasound medical imaging. A total of 160 New Zealand white rabbits were randomly divided into four groups of 40 each: (1) manual control group, (2) manual model group, (3) ultrasound guided control group, and (4) ultrasound guided model group. The subarachnoid hemorrhage was intentionally caused by double injection of blood into their cisterna magna. Then, basilar artery diameters were measured using magnetic resonance angiography before modeling and 5 days after modeling. The depth of needle entering into cisterna magna was determined during the process of ultrasound guided puncture. The mortality rates in manual control group and model group were 15 and 23 %, respectively. No rabbits were sacrificed in those two ultrasound guided groups. We found that the mortality rate in ultrasound guided groups decreased significantly compared to manual groups. Compared with diameters before modeling, the basilar artery diameters after modeling were significantly lower in manual and ultrasound guided model groups. The vasospasm aggravated and the proportion of severe vasospasms was greater in ultrasound guided model group than that of manual group. In manual model group, no vasospasm was found in 8 % of rabbits. The ultrasound guided double injection of blood into cisterna magna is a safe and effective rabbit model for treatment of cerebral vasospasm.

Intravitreal docosahexaenoic acid in a rabbit model: preclinical safety assessment.

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Rosa Dolz-Marco

Full Text Available PURPOSE: The purpose of the present study was to evaluate the retinal toxicity of a single dose of intravitreal docosahexaenoic acid (DHA in rabbit eyes over a short-term period. METHODS: Sixteen New Zealand albino rabbits were selected for this pre-clinical study. Six concentrations of DHA (Brudy Laboratories, Barcelona, Spain were prepared: 10 mg/50 µl, 5 mg/50 µl, 2'5 mg/50 µl, 50 µg/50 µl, 25 µg/50 µl, and 5 µg/50 µl. Each concentration was injected intravitreally in the right eye of two rabbits. As a control, the vehicle solution was injected in one eye of four animals. Retinal safety was studied by slit-lamp examination, and electroretinography. All the rabbits were euthanized one week after the intravitreal injection of DHA and the eyeballs were processed to morphologic and morphometric histological examination by light microscopy. At the same time aqueous and vitreous humor samples were taken to quantify the concentration of omega-3 acids by gas chromatography. Statistical analysis was performed by SPSS 21.0. RESULTS: Slit-lamp examination revealed an important inflammatory reaction on the anterior chamber of the rabbits injected with the higher concentrations of DHA (10 mg/50 µl, 5 mg/50 µl, 2'5 mg/50 µ Lower concentrations showed no inflammation. Electroretinography and histological studies showed no significant difference between control and DHA-injected groups except for the group injected with 50 µg/50 µl. CONCLUSIONS: Our results indicate that administration of intravitreal DHA is safe in the albino rabbit model up to the maximum tolerated dose of 25 µg/50 µl. Further studies should be performed in order to evaluate the effect of intravitreal injection of DHA as a treatment, alone or in combination, of different retinal diseases.

Rabbit defensin (NP-1) genetic engineering of plant

African Journals Online (AJOL)

Jane

2011-08-22

Aug 22, 2011 ... rabbit defensin has a significant toxic effect on mouse tumor cells .... Disease is one of the important factors which lead to decrease of .... Transgenic Nitrate Reductase Deficient Mutant of Chlorella ellipsoide. J. Agric.

Malignant neoplasms of decidual origin (deciduosarcomas) induced by estrogen-progestin-releasing intravaginal devices in rabbits.

OpenAIRE

Zook, B. C.; Spiro, I.; Hertz, R.

1987-01-01

A combination of estrogen and levonorgestrel was continuously delivered to 23 adult rabbits for up to 2 years via a Silastic ring device sutured into the vagina. Twenty-one control rabbits were given similar rings devoid of drugs. A marked decidual reaction of the endometrium occurred in 16 of 23 test rabbits. In 14 test rabbits (61%) malignant tumors developed of decidual type cells not heretofore described. The deciduosarcomas were composed of anaplastic cells that invaded the uterine walls...

Combination of aspartic acid and glutamic acid inhibits tumor cell proliferation.

Science.gov (United States)

Yamaguchi, Yoshie; Yamamoto, Katsunori; Sato, Yoshinori; Inoue, Shinjiro; Morinaga, Tetsuo; Hirano, Eiichi

2016-01-01

Placental extract contains several biologically active compounds, and pharmacological induction of placental extract has therapeutic effects, such as improving liver function in patients with hepatitis or cirrhosis. Here, we searched for novel molecules with an anti-tumor activity in placental extracts. Active molecules were separated by chromatographic analysis, and their antiproliferative activities were determined by a colorimetric assay. We identified aspartic acid and glutamic acid to possess the antiproliferative activity against human hepatoma cells. Furthermore, we showed that the combination of aspartic acid and glutamic acid exhibited enhanced antiproliferative activity, and inhibited Akt phosphorylation. We also examined in vivo tumor inhibition activity using the rabbit VX2 liver tumor model. The treatment mixture (emulsion of the amino acids with Lipiodol) administered by hepatic artery injection inhibited tumor cell growth of the rabbit VX2 liver. These results suggest that the combination of aspartic acid and glutamic acid may be useful for induction of tumor cell death, and has the potential for clinical use as a cancer therapeutic agent.

Selective enhancement of boron accumulation with boron-entrapped water-in-oil-water emulsion in VX-2 rabbit hepatic cancer model for BNCT

International Nuclear Information System (INIS)

Yanagie, Hironobu; Higashi, Shushi; Ikushima, Ichiro

2006-01-01

Tumor cell destruction in boron neutron-capture therapy (BNCT) is due to the nuclear reaction between 10 B and thermal neutrons. It is necessary for effective BNCT therapy to accumulate 10 B atoms in the tumor cells without affecting adjacent healthy cells. Water-in-oil-water (WOW) emulsion was used as the carrier of anti-cancer agents on arterial injections in clinical cancer treatment. In this study, we prepared 10 BSH entrapped WOW emulsion for selective arterial infusion for the treatment of hepatocellular carcinoma. WOW emulsion was administrated by arterial injections via proper hepatic artery. The anti-tumor activity of the emulsion was compared with 10 BSH-Lipiodol mix emulsion or 10 BSH solutions on VX-2 rabbit hepatic tumor models. The 10 B concentrations in VX-2 tumor on delivery with WOW emulsion was superior to those by conventional lipiodol mix emulsion. Electro-microscopic figures of WOW emulsion delineated the accumulation of fat droplets of WOW emulsion in the tumor site, but there was no accumulation of fat droplets in lipiodol emulsion. These results indicate that 10 B entrapped WOW emulsion is most useful carrier for arterial delivery of boron agents on BNCT to cancer. (author)

Rabbit model for human EBV-associated hemophagocytic syndrome (HPS): sequential autopsy analysis and characterization of IL-2-dependent cell lines established from herpesvirus papio-induced fatal rabbit lymphoproliferative diseases with HPS.

Science.gov (United States)

Hayashi, Kazuhiko; Jin, Zaishun; Onoda, Sachiyo; Joko, Hiromasa; Teramoto, Norihiro; Ohara, Nobuya; Oda, Wakako; Tanaka, Takehiro; Liu, Yi-Xuan; Koirala, Tirtha Raj; Oka, Takashi; Kondo, Eisaku; Yoshino, Tadashi; Takahashi, Kiyoshi; Akagi, Tadaatsu

2003-05-01

Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS) is often associated with fatal infectious mononucleosis or T-cell lymphoproliferative diseases (LPD). To elucidate the true nature of fatal LPD observed in Herpesvirus papio (HVP)-induced rabbit hemophagocytosis, reactive or neoplastic, we analyzed sequential development of HVP-induced rabbit LPD and their cell lines. All of the seven Japanese White rabbits inoculated intravenously with HVP died of fatal LPD 18 to 27 days after inoculation. LPD was also accompanied by hemophagocytic syndrome (HPS) in five of these seven rabbits. Sequential autopsy revealed splenomegaly and swollen lymph nodes, often accompanied by bleeding, which developed in the last week. Atypical lymphoid cells infiltrated many organs with a "starry sky" pattern, frequently involving the spleen, lymph nodes, and liver. HVP-small RNA-1 expression in these lymphoid cells was clearly demonstrated by a newly developed in situ hybridization (ISH) system. HVP-ISH of immunomagnetically purified lymphoid cells from spleen or lymph nodes revealed HVP-EBER1+ cells in each CD4+, CD8+, or CD79a+ fraction. Hemophagocytic histiocytosis was observed in the lymph nodes, spleen, bone marrow, and thymus. HVP-DNA was detected in the tissues and peripheral blood from the infected rabbits by PCR or Southern blot analysis. Clonality analysis of HVP-induced LPD by Southern blotting with TCR gene probe revealed polyclonal bands, suggesting polyclonal proliferation. Six IL-2-dependent rabbit T-cell lines were established from transplanted scid mouse tumors from LPD. These showed latency type I/II HVP infection and had normal karyotypes except for one line, and three of them showed tumorigenicity in nude mice. These data suggest that HVP-induced fatal LPD in rabbits is reactive polyclonally in nature.

A novel method for right one-lung ventilation modeling in rabbits.

Science.gov (United States)

Xu, Ze-Ping; Gu, Lian-Bing; Bian, Qing-Ming; Li, Peng-Yi; Wang, Li-Jun; Chen, Xiao-Xiang; Zhang, Jing-Yuan

2016-08-01

There is no standard method by which to establish a right one-lung ventilation (OLV) model in rabbits. In the present study, a novel method is proposed to compare with two other methods. After 0.5 h of baseline two-lung ventilation (TLV), 40 rabbits were randomly divided into sham group (TLV for 3 h as a contrast) and three right-OLV groups (right OLV for 3 h with different methods): Deep intubation group, clamp group and blocker group (deeply intubate the self-made bronchial blocker into the left main bronchus, the novel method). These three methods were compared using a number of variables: Circulation by heart rate (HR), mean arterial pressure (MAP); oxygenation by arterial blood gas analysis; airway pressure; lung injury by histopathology; and time, blood loss, success rate of modeling. Following OLV, compared with the sham group, arterial partial pressure of oxygen and arterial hemoglobin oxygen saturation decreased, peak pressure increased and lung injury scores were higher in three OLV groups at 3 h of OLV. All these indexes showed no differences between the three OLV groups. During right-OLV modeling, less time was spent in the blocker group (6±2 min), compared with the other two OLV groups (13±4 min in deep intubation group, Pright-OLV model in rabbits.

Computational Fluid Dynamics Modeling of Bacillus anthracis Spore Deposition in Rabbit and Human Respiratory Airways

Energy Technology Data Exchange (ETDEWEB)

Kabilan, Senthil; Suffield, Sarah R.; Recknagle, Kurtis P.; Jacob, Rick E.; Einstein, Daniel R.; Kuprat, Andrew P.; Carson, James P.; Colby, Sean M.; Saunders, James H.; Hines, Stephanie; Teeguarden, Justin G.; Straub, Tim M.; Moe, M.; Taft, Sarah; Corley, Richard A.

2016-09-30

Three-dimensional computational fluid dynamics and Lagrangian particle deposition models were developed to compare the deposition of aerosolized Bacillus anthracis spores in the respiratory airways of a human with that of the rabbit, a species commonly used in the study of anthrax disease. The respiratory airway geometries for each species were derived from computed tomography (CT) or µCT images. Both models encompassed airways that extended from the external nose to the lung with a total of 272 outlets in the human model and 2878 outlets in the rabbit model. All simulations of spore deposition were conducted under transient, inhalation-exhalation breathing conditions using average species-specific minute volumes. The highest exposure concentration was modeled in the rabbit based upon prior acute inhalation studies. For comparison, human simulation was also conducted at the same concentration. Results demonstrated that regional spore deposition patterns were sensitive to airway geometry and ventilation profiles. Due to the complex airway geometries in the rabbit nose, higher spore deposition efficiency was predicted in the upper conducting airways compared to the human at the same air concentration of anthrax spores. As a result, higher particle deposition was predicted in the conducting airways and deep lung of the human compared to the rabbit lung due to differences in airway branching pattern. This information can be used to refine published and ongoing biokinetic models of inhalation anthrax spore exposures, which currently estimate deposited spore concentrations based solely upon exposure concentrations and inhaled doses that do not factor in species-specific anatomy and physiology.

Esophageal replacement by hydroxylated bacterial cellulose patch in a rabbit model.

Science.gov (United States)

Zhu, Changlai; Liu, Fang; Qian, Wenbo; Wang, Yingjie; You, Qingsheng; Zhang, Tianyi; Li, Feng

2015-01-01

To repair esophageal defects by hydroxylated and kombucha-synthesized bacterial cellulose (HKBC) patch in a rabbit model. Semicircular esophageal defects 1 cm in length of the cervical esophagus were initially created in 18 Japanese big-ear rabbits and then repaired with HKBC patch grafts. The clinical outcomes including survival rate, weight change, food intake, and hematological and radiologic evaluation were observed. After X-ray evaluation, the rabbits were sacrificed sequentially at 1, 3, and 6 months for histopathologic analysis with light microscopy and scanning electron microscopy. Survival rate during the first month was 88.9% (n = 16). Two rabbits died from anastomotic leakage during the entire follow-up. Postoperatively, feeding function and body weight were gradually restored in the surviving animals. No hematological abnormalities were found, and no obvious anastomotic leakage, stenosis, or obstruction was observed under X-ray examination. The histopathologic results showed a progressive regeneration of the esophagus in the graft area, where the neo-esophagus tissue had characteristics similar to native esophageal tissue after 3 months of surgery. HKBC is beneficial for esophageal tissue regeneration and may be a promising material for esophageal reconstruction.

Possible interaction between myxomatosis and calicivirosis related to rabbit haemorrhagic disease affecting the European rabbit.

Science.gov (United States)

Marchandeau, S; Bertagnoli, S; Peralta, B; Boucraut-Baralon, C; Letty, J; Reitz, F

2004-11-06

Serological data on myxoma virus, rabbit haemorrhagic disease (RHD) virus and RHD-like viruses in juvenile rabbits (Oryctolagus cuniculus) trapped in 1995, 1996 and 1997 in two areas of France were analysed. For each disease, the effects of bodyweight, year, month and seropositivity for the other disease were modelled by using logistic regressions. In one area, a model including RHD seropositivity was selected to explain the myxoma virus seropositivity. Models including myxoma virus seropositivity were selected to explain the RHD seropositivity in both areas, and the odds of a rabbit being seropositive to both viruses were 5.1 and 8.4 times higher than the odds of a rabbit being seronegative to myxoma virus and seropositive to RHD. The year and bodyweight had significant effects for myxomatosis in one area and for RHD in both areas.

Effect of nano-silver hydrogel coating film on deep partial thickness scald model of rabbit

OpenAIRE

Peng Xi; Yan Li; Xiaojin Ge; Dandan Liu; Mingsan Miao

2018-01-01

Objective: Observing the effect of nano-silver hydrogel coating film on deep partial thickness scald model of rabbit. Method: We prepared boiling water scalded rabbits with deep II degree scald models and applied high, medium and low doses of nano-silver hydrogel coating film for different time and area. Then we compared the difference of burned paper weight before administration and after administration model burns, burn local skin irritation points infection, skin crusting and scabs from th...

Mechanical Characterization and Material Modeling of Diabetic Aortas in a Rabbit Model.

Science.gov (United States)

Tong, Jianhua; Yang, F; Li, X; Xu, X; Wang, G X

2018-03-01

Diabetes has been recognized as a major risk factor to cause macrovascular diseases and plays a key role in aortic wall remodeling. However, the effects of diabetes on elastic properties of aortas remain largely unknown and quantitative mechanical data are lacking. Thirty adult rabbits (1.6-2.2 kg) were collected and the type 1 diabetic rabbit model was induced by injection of alloxan. A total of 15 control and 15 diabetic rabbit (abdominal) aortas were harvested. Uniaxial and biaxial tensile tests were performed to measure ultimate tensile strength and to characterize biaxial mechanical behaviors of the aortas. A material model was fitted to the biaxial experimental data to obtain constitutive parameters. Histological and mass fraction analyses were performed to investigate the underlying microstructure and dry weight percentages of elastin and collagen in the control and the diabetic aortas. No statistically significant difference was found in ultimate tensile strength between the control and the diabetic aortas. Regarding biaxial mechanical responses, the diabetic aortas exhibited significantly lower extensibility and significantly higher tissue stiffness than the control aortas. Notably, tissue stiffening occurred in both circumferential and axial directions for the diabetic aortas; however, mechanical anisotropy does not change significantly. The material model was able to fit biaxial experimental data very well. Histology showed that a number of isolated foam cells were embedded in the diabetic aortas and hyperplasia of collagen was identified. The dry weight percentages of collagen within the diabetic aortas increased significantly as compared to the control aortas, whereas no significant change was found for that of elastin. Our data suggest that the diabetes impairs elastic properties and alters microstructure of the aortas and consequently, these changes may further contribute to complex aortic wall remodeling.

A rabbit model of fatal hypothyroidism mimicking "myxedema coma" established by microscopic total thyroidectomy.

Science.gov (United States)

Ono, Yosuke; Fujita, Masanori; Ono, Sachiko; Ogata, Sho; Tachibana, Shoichi; Tanaka, Yuji

2016-06-30

Myxedema coma (MC) is a life-threatening endocrine crisis caused by severe hypothyroidism. However, validated diagnostic criteria and treatment guidelines for MC have not been established owing to its rarity. Therefore, a valid animal model is required to investigate the pathologic and therapeutic aspects of MC. The aim of the present study was to establish an animal model of MC induced by total thyroidectomy. We utilized 14 male New Zealand White rabbits anesthetized via intramuscular ketamine and xylazine administration. A total of 7 rabbits were completely thyroidectomized under a surgical microscope (thyroidectomized group) and the remainder underwent sham operations (control group). The animals in both groups were monitored without thyroid hormone replacement for 15 weeks. Pulse rate, blood pressure, body temperature, and electrocardiograms (ECG) were recorded and blood samples were taken from the jugular vein immediately prior to the thyroidectomy and 2 and 4 weeks after surgery. The thyroidectomized rabbits showed a marked reduction of serum thyroxine levels at 4 weeks after the surgical procedure vs. controls (0.50±0.10 vs. 3.32±0.68 μg/dL, pmyxedema heart. In summary, we have established a rabbit model of fatal hypothyroidism mimicking MC, which may facilitate pathophysiological and molecular investigations of MC and evaluations of new therapeutic interventions.

A novel rabbit anti-hepatocyte growth factor monoclonal neutralizing antibody inhibits tumor growth in prostate cancer cells and mouse xenografts

International Nuclear Information System (INIS)

Yu, Yanlan; Chen, Yicheng; Ding, Guoqing; Wang, Mingchao; Wu, Haiyang; Xu, Liwei; Rui, Xuefang; Zhang, Zhigen

2015-01-01

The hepatocyte growth factor and its receptor c-Met are correlated with castration-resistance in prostate cancer. Although HGF has been considered as an attractive target for therapeutic antibodies, the lack of cross-reactivity of monoclonal antibodies with human/mouse HGFs is a major obstacle in preclinical developments. We generated a panel of anti-HGF RabMAbs either blocking HGF/c-Met interaction or inhibiting c-Met phosphorylation. We selected one RabMAb with mouse cross-reactivity and demonstrated that it blocked HGF-stimulated downstream activation in PC-3 and DU145 cells. Anti-HGF RabMAb inhibited not only the growth of PC-3 cells but also HGF-dependent proliferation in HUVECs. We further demonstrated the efficacy and potency of the anti-HGF RabMAb in tumor xenograft mice models. Through these in vitro and in vivo experiments, we explored a novel therapeutic antibody for advanced prostate cancer. - Highlights: • HGF is an attractive target for castration-refractory prostate cancer. • We generated and characterized a panel of anti-HGF rabbit monoclonal antibodies. • More than half of these anti-HGF RabMAbs was cross-reactive with mouse HGF. • Anti-HGF RabMAb blocks HGF-stimulated phosphorylation and cell growth in vitro. • Anti-HGF RabMAb inhibits tumor growth and angiogenesis in xenograft mice

A novel rabbit anti-hepatocyte growth factor monoclonal neutralizing antibody inhibits tumor growth in prostate cancer cells and mouse xenografts

Energy Technology Data Exchange (ETDEWEB)

Yu, Yanlan; Chen, Yicheng; Ding, Guoqing; Wang, Mingchao; Wu, Haiyang; Xu, Liwei; Rui, Xuefang; Zhang, Zhigen, E-mail: srrshurology@163.com

2015-08-14

The hepatocyte growth factor and its receptor c-Met are correlated with castration-resistance in prostate cancer. Although HGF has been considered as an attractive target for therapeutic antibodies, the lack of cross-reactivity of monoclonal antibodies with human/mouse HGFs is a major obstacle in preclinical developments. We generated a panel of anti-HGF RabMAbs either blocking HGF/c-Met interaction or inhibiting c-Met phosphorylation. We selected one RabMAb with mouse cross-reactivity and demonstrated that it blocked HGF-stimulated downstream activation in PC-3 and DU145 cells. Anti-HGF RabMAb inhibited not only the growth of PC-3 cells but also HGF-dependent proliferation in HUVECs. We further demonstrated the efficacy and potency of the anti-HGF RabMAb in tumor xenograft mice models. Through these in vitro and in vivo experiments, we explored a novel therapeutic antibody for advanced prostate cancer. - Highlights: • HGF is an attractive target for castration-refractory prostate cancer. • We generated and characterized a panel of anti-HGF rabbit monoclonal antibodies. • More than half of these anti-HGF RabMAbs was cross-reactive with mouse HGF. • Anti-HGF RabMAb blocks HGF-stimulated phosphorylation and cell growth in vitro. • Anti-HGF RabMAb inhibits tumor growth and angiogenesis in xenograft mice.

Establishment of a head injury by club model in rabbits and experimental conditions

International Nuclear Information System (INIS)

Cao Yunxing; Xi Huanjiu; Zhang Jing; Li Hongwei; Yin Zhiyong; Zhao Hui

2013-01-01

Objective: To establish an animal model to replicate the injury by club in forensic medicine. Methods: Twenty-four New Zealand white rabbits were divided into control group (n=4), minor injury group (n=10), and severe injury group (n=10). Based on the BIM-Ⅱ Horizontal Bio-impact Machine, a self-designed iron bar was used to produce head injury by club. Six hours after injury, all the rabbits were subjected to a CT examination and dissected to observe the injury morphology and undergo routine pathological examination. Four control, six minor and severe rabbits were given moisture content examination. Results: Varying degrees of positive signs of the nervous system were observed in all the injured rabbits within 6 hours. The mortality rate was 1/10 in the minor injury group and 6/10 in the severe injury group. The morphological changes consisted of different levels of scalp hematoma, skull fracture, epidural hematoma, subdural hematoma, subarachnoid hemorrhage and brain injury. The difference in moisture content between the three groups was of statistical significance. Conclusion: Under the rigidly-controlled experimental condition, this animal model produces good reproducibility and stable results. Meanwhile, it can simulate the morphology of injury by club and be used to study the mechanism of injury by club in forensic medicine. (authors)

Autologous tenocyte therapy for experimental Achilles tendinopathy in a rabbit model.

Science.gov (United States)

Chen, Jimin; Yu, Qian; Wu, Bing; Lin, Zhen; Pavlos, Nathan J; Xu, Jiake; Ouyang, Hongwei; Wang, Allan; Zheng, Ming H

2011-08-01

Tendinopathy of the Achilles tendon is a chronic degenerative condition that frequently does not respond to treatment. In the current study, we propose that autologous tenocytes therapy (ATT) is effective in treating tendon degeneration in a collagenase-induced rabbit Achilles tendinopathy model. Chronic tendinopathy was created in the left Achilles tendon of 44 rabbits by an intratendonous injection of type I collagenase. Forty-two rabbits were randomly allocated into three groups of 14 and received control treatment; autologous tenocytes digested from tendon tissue; and autologous tenocytes digested from epitendineum tissue. For cell tracking in vivo, the remaining two animals were injected with autologous tenocytes labeled with a nano-scale super-paramagnetic iron oxide (Feridex). Rabbits were sacrificed at 4 and 8 weeks after the therapeutic injection, and tendon tissue was analyzed by histology, immunostaining, and biomechanical testing to evaluate tissue repair. Autologous tenocyte treatment improved tendon remodeling, histological outcomes, collagen content, and tensile strength of tendinopathic Achilles tendons. Injected tenocytes were integrated into tendon matrix and could be tracked up to 8 weeks in vivo. Immunohistochemistry showed that ATT improved type I collagen expression in repaired tendon but did not affect type III collagen and secreted protein, acidic and rich in cysteine expression. ATT may be a useful treatment of chronic Achilles tendinopathy.

Changes in Hepatic Blood Flow During Transcatheter Arterial Infusion with Heated Saline in Hepatic VX2 Tumor

International Nuclear Information System (INIS)

Cao Wei; Li Jing; Wu Zhiqun; Zhou Changxi; Liu Xi; Wan Yi; Duan Yunyou

2013-01-01

Purpose. This study evaluates the influence of transcatheter arterial infusion with heated saline on hepatic arterial and portal venous blood flows to tumor and normal hepatic tissues in a rabbit VX2 tumor model. Methods. All animal experiments were approved by the institutional animal care and use committee. Twenty rabbits with VX2 liver tumors were divided into the following two groups: (a) the treated group (n = 10), which received a 60 mL transarterial injection of 60 °C saline via the hepatic artery; (b) the control group (n = 10), which received a 60 mL injection of 37 °C saline via the hepatic artery. Using ultrasonography, the blood flows in both the portal vein and hepatic artery were measured, and the changes in the hemodynamic indices were recorded before and immediately after the injection. The changes in the tumor and normal liver tissues of the two groups were histopathologically examined by hematoxylin and eosin staining after the injection. Results. After the transcatheter arterial heated infusion, there was a decrease in the hepatic arterial blood flow to the tumor tissue, a significant decrease in the hepatic artery mean velocity (P < 0.05), and a significant increase in the resistance index (P < 0.05). On hematoxylin and eosin staining, there were no obvious signs of tissue destruction in the normal liver tissue or the tumor tissue after heated perfusion, and coagulated blood plasma was observed in the cavities of intratumoral blood vessels in the treated group. Conclusions. The changes in tumor blood flow in the rabbit VX2 tumor model were presumably caused by microthrombi in the tumor vessels, and the portal vein likely mediated the heat loss in normal liver tissue during the transarterial heated infusion.

Changes in Hepatic Blood Flow During Transcatheter Arterial Infusion with Heated Saline in Hepatic VX2 Tumor

Energy Technology Data Exchange (ETDEWEB)

Cao Wei, E-mail: cawe-001@163.com [Tangdu Hospital, The Fourth Military Medical University, Department of Interventional Radiology (China); Li Jing, E-mail: lijing02@fmmu.edu.cn [Tangdu Hospital, The Fourth Military Medical University, Department of Burn and Plastic Surgery (China); Wu Zhiqun, E-mail: zhiqunwu@fmmu.edu.cn [Tangdu Hospital, The Fourth Military Medical University, Department of Interventional Radiology (China); Zhou Changxi, E-mail: changxizhou@163.com [Chinese PLA General Hospital, Department of Respiratory Disease (China); Liu Xi, E-mail: xiliu@fmmu.edu.cn [Tangdu Hospital, The Fourth Military Medical University, Department of Ultrasound Diagnostics (China); Wan Yi, E-mail: yiwan@163.com [The Fourth Military Medical University, Department of Health Statistics, Institute for Health Informatics (China); Duan Yunyou, E-mail: yunyouduan@fmmu.edu.cn [Tangdu Hospital, The Fourth Military Medical University, Department of Ultrasound Diagnostics (China)

2013-06-15

Purpose. This study evaluates the influence of transcatheter arterial infusion with heated saline on hepatic arterial and portal venous blood flows to tumor and normal hepatic tissues in a rabbit VX2 tumor model. Methods. All animal experiments were approved by the institutional animal care and use committee. Twenty rabbits with VX2 liver tumors were divided into the following two groups: (a) the treated group (n = 10), which received a 60 mL transarterial injection of 60 Degree-Sign C saline via the hepatic artery; (b) the control group (n = 10), which received a 60 mL injection of 37 Degree-Sign C saline via the hepatic artery. Using ultrasonography, the blood flows in both the portal vein and hepatic artery were measured, and the changes in the hemodynamic indices were recorded before and immediately after the injection. The changes in the tumor and normal liver tissues of the two groups were histopathologically examined by hematoxylin and eosin staining after the injection. Results. After the transcatheter arterial heated infusion, there was a decrease in the hepatic arterial blood flow to the tumor tissue, a significant decrease in the hepatic artery mean velocity (P < 0.05), and a significant increase in the resistance index (P < 0.05). On hematoxylin and eosin staining, there were no obvious signs of tissue destruction in the normal liver tissue or the tumor tissue after heated perfusion, and coagulated blood plasma was observed in the cavities of intratumoral blood vessels in the treated group. Conclusions. The changes in tumor blood flow in the rabbit VX2 tumor model were presumably caused by microthrombi in the tumor vessels, and the portal vein likely mediated the heat loss in normal liver tissue during the transarterial heated infusion.

High rabbit abundance proves detrimental to the population growth rate in European rabbit (Oryctolagus cuniculus L. extensive breeding enclosures

Directory of Open Access Journals (Sweden)

L. Ruiz-Aizpurua

2014-09-01

Full Text Available The European rabbit (Oryctolagus cuniculus L. is a key prey species in Mediterranean ecosystems that has declined in its natural ranges as a result of diseases and loss of habitat. This situation has led to the production of wild rabbits in enclosures in which they can acclimate and breed. The efficiency of these enclosures as extensive breeding systems is defined by their population growth rate (PGR. The aim of this study is to analyse the effect of rabbit abundance on the PGR. This has been done by creating general linear models to explain autumn and spring PGR with the use of rabbit abundance estimates, enclosure size, aerial predation and previous PGR as possible explanatory variables. Rabbit abundance and enclosure size negatively affected the autumn PGR, while only rabbit abundance affected the spring PGR in the best-fit models. It is suggested that maintaining rabbit densities at fewer than 30 rabbits per hectare might help to optimise the efficiency inside enclosures.

Detection of thrombosis and plaque rupture in atherosclerotic rabbit model by using 3.0 T MR imaging

International Nuclear Information System (INIS)

Ma Xiaohai; Zhang Zhaoqi; Zhao Lei; Zhao Quanming; Shang Jianfeng; Feng Tingting; Zeng Conghe

2011-01-01

Objective: To explore the imaging of the thrombosis after pharmacological triggering of plaque rupture in atherosclerotic rabbit model by using 3.0 T high-resolution magnetic resonance imaging. Methods: Twenty male New Zealand white rabbits were divided into an experimental group (n=16) and a control group (n=4). The aortic wall injuries were induced by an intravascular balloon in experimental group rabbits after high cholesterol diet. The pharmacological triggering with Russell's viper venom and histamine was performed after 3 months of establishment of model. All of the animals underwent pre-trigger and post-trigger MR examinations including 3D time of fight (3D TOF), T 1 WI, T 2 WI and post contrast T 1 WI. Euthanasia was performed in all rabbits and gross anatomy and histological specimen of aorta were obtained. Comparing the location and length of the thrombus between MRI images and histopathology was used Pearson test. Comparing the calculated indexes of abdominal aorta between rabbits with and without thrombosis was used AVONA test and LSD-t test. Results: After triggering, 8 in 14 survived rabbits developed thrombosis in experimental group, meanwhile, no thrombus was found in control group. The accuracy of multi-sequences MRI for detecting of thrombus was 87.1% (27/31). MRI data correlated with the histopathology regarding thrombus length (r=0.85, P 2 vs. (8.93±5.36) mm 2 , P<0.01]. Conclusion: MRI is useful tool to determine the thrombosis and plaque rupture in atherosclerotic rabbit model. (authors)

Tissue engineered tumor models.

Science.gov (United States)

Ingram, M; Techy, G B; Ward, B R; Imam, S A; Atkinson, R; Ho, H; Taylor, C R

2010-08-01

Many research programs use well-characterized tumor cell lines as tumor models for in vitro studies. Because tumor cells grown as three-dimensional (3-D) structures have been shown to behave more like tumors in vivo than do cells growing in monolayer culture, a growing number of investigators now use tumor cell spheroids as models. Single cell type spheroids, however, do not model the stromal-epithelial interactions that have an important role in controlling tumor growth and development in vivo. We describe here a method for generating, reproducibly, more realistic 3-D tumor models that contain both stromal and malignant epithelial cells with an architecture that closely resembles that of tumor microlesions in vivo. Because they are so tissue-like we refer to them as tumor histoids. They can be generated reproducibly in substantial quantities. The bioreactor developed to generate histoid constructs is described and illustrated. It accommodates disposable culture chambers that have filled volumes of either 10 or 64 ml, each culture yielding on the order of 100 or 600 histoid particles, respectively. Each particle is a few tenths of a millimeter in diameter. Examples of histological sections of tumor histoids representing cancers of breast, prostate, colon, pancreas and urinary bladder are presented. Potential applications of tumor histoids include, but are not limited to, use as surrogate tumors for pre-screening anti-solid tumor pharmaceutical agents, as reference specimens for immunostaining in the surgical pathology laboratory and use in studies of invasive properties of cells or other aspects of tumor development and progression. Histoids containing nonmalignant cells also may have potential as "seeds" in tissue engineering. For drug testing, histoids probably will have to meet certain criteria of size and tumor cell content. Using a COPAS Plus flow cytometer, histoids containing fluorescent tumor cells were analyzed successfully and sorted using such criteria.

Antiarrhythmic properties of a rapid delayed-rectifier current activator in rabbit models of acquired long QT syndrome

DEFF Research Database (Denmark)

Diness, Thomas G; Yeh, Yung-Hsin; Qi, Xiao Yan

2008-01-01

effect of a novel compound (NS1643) that activates the rapid delayed-rectifier K+ current, I(Kr), in two rabbit models of acquired LQTS. METHODS AND RESULTS: We used two clinically relevant in vivo rabbit models of TdP in which we infused NS1643 or vehicle: (i) three-week atrioventricular block...

Studies on uptake and distribution of chemotherapeutic agents to malignant tumors of the head and neck in rabbits, 2. /sup 3/H-Adriamycin

Energy Technology Data Exchange (ETDEWEB)

Yamada, R. (Gifu Univ. (Japan). Faculty of Medicine)

1981-09-01

Experiments were performed to investigate incorporation and distribution of chemotherapeutic agents into malignant tumors of the head and neck by microautoradiographic and electron microscopic-autoradiographic observations of VX2 carcinoma transplanted in the lower genial region of rabbits after injection of /sup 3/H-Adriamycin as a tracer. The following findings were obtained. 1. On microautoradiograms, /sup 3/H-Adriamycin was distributed predominantly in the nucleoplasm, rather than in the cytoplasm, of tumor tissues. 2. At the ultrastructural level, /sup 3/H-Adriamycin was localized in the nuclear membrane and nucleoli within the nucleoplasm and in the rough endoplasmic reticulum and secretory granules within the cytoplasm. 3. These findings seem to indicate that Adriamycin may inhibit the synthesis of DNA and RNA in the nucleoplasm.

rhBMP-2 (ACS and CRM formulations) overcomes pseudarthrosis in a New Zealand white rabbit posterolateral fusion model.

Science.gov (United States)

Lawrence, James P; Waked, Walid; Gillon, Thomas J; White, Andrew P; Spock, Christopher R; Biswas, Debdut; Rosenberger, Patricia; Troiano, Nancy; Albert, Todd J; Grauer, Jonathan N

2007-05-15

The study design consisted of a New Zealand white rabbit model of pseudarthrosis repair. Study groups consisting of no graft, autograft, or recombinant human bone morphogenetic protein-2 (rhBMP-2) with absorbable collagen sponge (ACS) or compression resistant matrix (CRM) were evaluated. To evaluate the relative efficacy of bone graft materials (autograft, ACS, and CRM). rhBMP-2 has been shown to have a 100% fusion rate in a primary rabbit fusion model, even in the presence of nicotine, which is known to inhibit fusion. Seventy-two New Zealand white rabbits underwent posterolateral lumbar fusion with iliac crest autograft. To establish pseudarthroses, nicotine was administered to all animals. At 5 weeks, the spines were explored and all pseudarthroses were redecorticated and implanted with no graft, autograft, rhBMP-2/ACS, or rhBMP-2/CRM. At 10 weeks, fusions were assessed by manual palpation and histology. Eight rabbits (11%) were lost to complications. At 5 weeks, 66 (97%) had pseudarthroses. At 10 weeks, attempted pseudarthrosis repairs were fused in 1 of 16 of no graft rabbits (6%), 5 of 17 autograft rabbits (29%), and 31 of 31 rhBMP-2 rabbits (with ACS or CRM) (100%). Histologic analysis demonstrated more mature bone formation in the rhBMP-2 groups. The 2 rhBMP-2 formulations led to significantly higher fusion rates and histologic bone formation than no graft and autograft controls in this pseudarthrosis repair model.

VX2 Carcinoma in rabbit liver: Different radiologic features according to innoculation methods

International Nuclear Information System (INIS)

Lee, Joon Woo; Chung, Jin Wook; Choi, Guk Myeong; Kim, Chong Jai; Kim, Se Hyung; Choi, Joon Il; Lee, Kyoung Ho; Kim, Seung Hyup; Park, Jae Hyung

2000-01-01

To investigate radiologic features about hepatic VX2 carcinoma induced by two methods, direct intraparenchymal innoculation vs transpotal approach, focus on enhancement pattern and comparison of each imaging modalities and innoculation methods. VX2 carcinomas were induced in 11 rabbit livers by direct inoculation (n=7) or infusion into mesenteric vein (n=4). After two weeks, spiral CT, digital subtraction angiography (DSA), intravenous contrast-enhanced power Doppler sonography, intraarterial CO 2 sonography were done. The enhancement patterns were assessed independently and correlated with histopathologic features. With direct intraprenchymal innoculation, localized hepatic VX2 tumors were developed. Considering all imaging modalities, six of 7 tumors appeared peripheral hypervascularity, one hypovascularity. On pathologic and radiologic correlations, the enhancing portions of 4 tumors corresponded to viable tumor and pseudo-capsule portion, the other enhancing portions of 2 tumors corresponded to sinusoidal vascular spaces. With the transportal approaches, diffuse hepatic tumors were developed. Spiral CT and DSA revealed these tumors as marked peripheral hypervascular tumors with multiple A-P shunts. On pathologic findings, multiple thin walled sinusoidal spaces were seen at periphery of nodule. Spiral CT was superior to the other modalities in evaluation of enhancement characteristics. VX2 carcinomas in rabbit livers showed different radiologic and histopathologic features according to the innoculation methods.

Modeling Chronic Dacryocystitis in Rabbits by Nasolacrimal Duct Obstruction with Self-Curing Resin

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Kai Hou

2017-01-01

Full Text Available We established a chronic dacryocystitis model by injecting of 0.05, 0.1, and 0.15 ml self-curing resin via the lacrimal punctum in rabbits. Animals were randomized into four groups (n=11 animals/group. The control group received 0.15 ml normal saline. Within three months postinjection, epiphora and eye discharge were observed. At the 90th day postlacrimal passage irrigation, CT dacryocystography was performed to find changes in the lacrimal image, and hematoxylin and eosin staining was made to identify pathological changes of the lacrimal sac. Three months postinjection, the rabbits in control group and those who received 0.05 and 0.1 ml self-curing resin failed to develop chronic dacryocystitis. However, 8/11 (72.7% rabbits those received 0.15 ml self-curing resin were symptomatic and showed complete reflux in lacrimal passage irrigation, indicating the obstruction of the nasolacrimal duct. CT dacryocystography showed that the obstruction was present only in the animals with chronic dacryocystitis. Pathological examinations of chronic dacryocystitis also revealed significantly inflammatory changes, such as mucus epithelium thickening, irregular papillary proliferation, and submucosal fibrous deposition. Local injection of 0.15 ml self-curing resin can induce permanent obstruction of the nasolacrimal duct in rabbits and establish a model of chronic dacryocystitis.

The intervention research on treatment by Xianchen to rabbits model of chemotherapeutic phlebitis.

Science.gov (United States)

Zhang, Jing; Shen, Juan; Yin, Weiwei; Wei, Xiaoyu; Wu, Ligao; Liu, Hao

2016-08-01

To develop a chemotherapeutics induced phlebitis and explore the effects of Xianchen on the phlebitis treatment. Forty-eight rabbits were divided into two series. Phlebitis model induced by vincristine was established at each series. The first series had 24 rabbits, which were divided into four groups (6 hours, 12 hours, 18 hours, 24 hours) after vincristine infusion. The grades of phlebitis through visual observation and histopathological examination were observed. The second series had also 24 rabbits. Interventions were performed 12 hours after vincristine infusion. These rabbits were randomly divided into four groups, according to treatment: Hirudoid (bid), Xianchen (daily), Xianchen (tid), Xianchen (five times a day). Four days after intervention, the venous injury through visual observation and histopathological examination were evaluated. Series 1: Phlebitis appeared 12 hours after infusion of vincristine through visual observation. There was a significant difference (pphlebitis appeared early. Xianchen can treat vincristine induced phlebitis, as well as Hirudoid. It is particularly effective in the treatment of edema, and there is a remarkable dose-response relationship.

Radioprotection of salivary glands by S-2-(3-aminopropylamino)-ethylphosphorothioic (amifostine) obtained in a rabbit animal model

International Nuclear Information System (INIS)

Bohuslavizki, Karl H.; Klutmann, Susanne; Jenicke, Lars; Brenner, Winfried; Feyerabend, Bernd; Henze, Eberhard; Clausen, Malte

1999-01-01

Background: Impairment of salivary gland function following high-dose radioiodine treatment (HDRIT) is a well-recognized side effect of the treatment. Because differentiated thyroid cancer has an excellent prognosis, reduction of long-term side-effects is mandatory. Therefore, the aim of this study was to investigate the radioprotective effect of amifostine in a rabbit animal model. Methods: Salivary gland scintigraphy was performed in a total of 16 New Zealand White rabbits. Uptake of 99m Tc-pertechnetate was calculated in percentage of injected activity as a quantitative measure of both salivary gland and thyroid function. Reproducibility of salivary gland scintigraphy was evaluated in one rabbit without any intervention. Fifteen rabbits were studied prior to and up to 6 months after high-dose radioiodine treatment applying 2 GBq 131 I. Ten animals received 200 mg/kg amifostine prior to high-dose radioiodine therapy, and 5 served as controls. Salivary glands were examined histopathologically. Results: Variation coefficient of parenchymal function was less than 3.8% in salivary glands. Prior to HDRIT, thyroid uptake was 0.417 ± 0.373% and 0.421 ± 0.241% in control and amifostine-treated rabbits, respectively. Four weeks after HDRIT, complete ablation of the thyroid was achieved in both groups. Prior to HDRIT, uptake of 99m Tc-pertechnetate in salivary glands of five control rabbits was not significantly different from ten amifostine-treated rabbits. In control rabbits 6 months after HDRIT, parenchymal function was reduced significantly (p 0.05) in parotid and submandibular glands, respectively. Histopathologically, marked lipomatosis was observed in control animals but was negligible in amifostine-treated animals. Conclusion: Parenchymal damage in salivary glands induced by high-dose radioiodine treatment can be significantly reduced by amifostine in this rabbit animal model. This corresponds to data obtained in patients with differentiated thyroid cancer

Anatomic and histological study of the rabbit mandible as an experimental model for wound healing and surgical therapies.

Science.gov (United States)

Campillo, V-E; Langonnet, S; Pierrefeu, A; Chaux-Bodard, A-G

2014-10-01

The rabbit is one of the most widely used models for studying bone remodeling or dental implant osseointegration but very few data are available about the rabbit's mandible. The aim of this work was to describe the anatomy of the rabbit mandible and to estimate the available bone volume for experimental studies. First, with a dissection, the morphology of the mandible was described and the mental foramen, the position of the main salivary glands and muscular insertions were located. Then, by X-ray imaging, the position of the inferior alveolar canal, the dental root courses and volume and bone density were described. Finally, with frontal sections of the mandible body, the rabbit's dental and alveolar bone histological structure were assessed. Thus, the relevance of the rabbit mandible as an experimental model for wound healing or surgical therapies was discussed. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

A Parsimonious Model of the Rabbit Action Potential Elucidates the Minimal Physiological Requirements for Alternans and Spiral Wave Breakup.

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Gray, Richard A; Pathmanathan, Pras

2016-10-01

Elucidating the underlying mechanisms of fatal cardiac arrhythmias requires a tight integration of electrophysiological experiments, models, and theory. Existing models of transmembrane action potential (AP) are complex (resulting in over parameterization) and varied (leading to dissimilar predictions). Thus, simpler models are needed to elucidate the "minimal physiological requirements" to reproduce significant observable phenomena using as few parameters as possible. Moreover, models have been derived from experimental studies from a variety of species under a range of environmental conditions (for example, all existing rabbit AP models incorporate a formulation of the rapid sodium current, INa, based on 30 year old data from chick embryo cell aggregates). Here we develop a simple "parsimonious" rabbit AP model that is mathematically identifiable (i.e., not over parameterized) by combining a novel Hodgkin-Huxley formulation of INa with a phenomenological model of repolarization similar to the voltage dependent, time-independent rectifying outward potassium current (IK). The model was calibrated using the following experimental data sets measured from the same species (rabbit) under physiological conditions: dynamic current-voltage (I-V) relationships during the AP upstroke; rapid recovery of AP excitability during the relative refractory period; and steady-state INa inactivation via voltage clamp. Simulations reproduced several important "emergent" phenomena including cellular alternans at rates > 250 bpm as observed in rabbit myocytes, reentrant spiral waves as observed on the surface of the rabbit heart, and spiral wave breakup. Model variants were studied which elucidated the minimal requirements for alternans and spiral wave break up, namely the kinetics of INa inactivation and the non-linear rectification of IK.The simplicity of the model, and the fact that its parameters have physiological meaning, make it ideal for engendering generalizable mechanistic

Effect of Hydroxyapatite on Bone Integration in a Rabbit Tibial Defect Model

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Sohn, Sung-Keun; Kim, Kyung-Taek; Kim, Chul-Hong; Ahn, Hee-Bae; Rho, Mee-Sook; Jeong, Min-Ho; Sun, Sang-Kyu

2010-01-01

Background The aim of the present study was to prepare hydroxyapatite (HA) and then characterize its effect on bone integration in a rabbit tibial defect model. The bone formation with different designs of HA was compared and the bony integration of several graft materials was investigated qualitatively by radiologic and histologic study. Methods Ten rabbits were included in this study; two holes were drilled bilaterally across the near cortex and the four holes in each rabbit were divided into four treatment groups (HAP, hydroxyapatite powder; HAC, hydroxyapatite cylinder; HA/TCP, hydroxyapatite/tri-calcium phosphate cylinder, and titanium cylinder). The volume of bone ingrowth and the change of bone mineral density were statistically calculated by computed tomography five times for each treatment group at 0, 2, 4, 6, and 8 weeks after grafting. Histologic analysis was performed at 8 weeks after grafting. Results The HAP group showed the most pronounced effect on the bone ingrowth surface area, which seen at 4, 6, and 8 weeks after graft (p 0.05). On histological examination, the HAP group revealed well-recovered cortical bone, but the bone was irregularly thickened and haphazardly admixed with powder. The HAC group showed similar histological features to those of the HA/TCP group; the cortical surface of the newly developed bone was smooth and the bone matrix on the surface of the cylinder was regularly arranged. Conclusions We concluded that both the hydroxyapatite powder and cylinder models investigated in our study may be suitable as a bone substitute in the rabbit tibial defect model, but their characteristic properties are quite different. In contrast to hydroxyapatite powder, which showed better results for the bone ingrowth surface, the hydroxyapatite cylinder showed better results for the sustained morphology. PMID:20514266

Analysis of Host Range Restriction Determinants in the Rabbit Model: Comparison of Homologous and Heterologous Rotavirus Infections

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Ciarlet, Max; Estes, Mary K.; Barone, Christopher; Ramig, Robert F.; Conner, Margaret E.

1998-01-01

The main limitation of both the rabbit and mouse models of rotavirus infection is that human rotavirus (HRV) strains do not replicate efficiently in either animal. The identification of individual genes necessary for conferring replication competence in a heterologous host is important to an understanding of the host range restriction of rotavirus infections. We recently reported the identification of the P type of the spike protein VP4 of four lapine rotavirus strains as being P[14]. To determine whether VP4 is involved in host range restriction in rabbits, we evaluated infection in rotavirus antibody-free rabbits inoculated orally with two P[14] HRVs, PA169 (G6) and HAL1166 (G8), and with several other HRV strains and animal rotavirus strains of different P and G types. We also evaluated whether the parental rhesus rotavirus (RRV) (P5B[3], G3) and the derived RRV-HRV reassortant candidate vaccine strains RRV × D (G1), RRV × DS-1 (G2), and RRV × ST3 (G4) would productively infect rabbits. Based on virus shedding, limited replication was observed with the P[14] HRV strains and with the SA11 Cl3 (P[2], G3) and SA11 4F (P6[1], G3) animal rotavirus strains, compared to the homologous ALA strain (P[14], G3). However, even limited infection provided complete protection from rotavirus infection when rabbits were challenged orally 28 days postinoculation (DPI) with 103 50% infective doses of ALA rabbit rotavirus. Other HRVs did not productively infect rabbits and provided no significant protection from challenge, in spite of occasional seroconversion. Simian RRV replicated as efficiently as lapine ALA rotavirus in rabbits and provided complete protection from ALA challenge. Live attenuated RRV reassortant vaccine strains resulted in no, limited, or productive infection of rabbits, but all rabbits were completely protected from heterotypic ALA challenge. The altered replication efficiency of the reassortants in rabbits suggests a role for VP7 in host range restriction

Analysis of Long-Term Electrocardiographic Data in a Rabbit Model of Heart Failure

National Research Council Canada - National Science Library

Schuckers, Stephanie

2001-01-01

... was progressively induced with doxorubicin in a rabbit model, and electrocardiographic progressions from normal state to diseased state were continuously tracked, Automated methods for analyzing...

Radioprotection of salivary glands by S-2-(3-aminopropylamino)-ethylphosphorothioic (amifostine) obtained in a rabbit animal model

Energy Technology Data Exchange (ETDEWEB)

Bohuslavizki, Karl H; Klutmann, Susanne; Jenicke, Lars; Brenner, Winfried; Feyerabend, Bernd; Henze, Eberhard; Clausen, Malte

1999-08-01

Background: Impairment of salivary gland function following high-dose radioiodine treatment (HDRIT) is a well-recognized side effect of the treatment. Because differentiated thyroid cancer has an excellent prognosis, reduction of long-term side-effects is mandatory. Therefore, the aim of this study was to investigate the radioprotective effect of amifostine in a rabbit animal model. Methods: Salivary gland scintigraphy was performed in a total of 16 New Zealand White rabbits. Uptake of {sup 99m}Tc-pertechnetate was calculated in percentage of injected activity as a quantitative measure of both salivary gland and thyroid function. Reproducibility of salivary gland scintigraphy was evaluated in one rabbit without any intervention. Fifteen rabbits were studied prior to and up to 6 months after high-dose radioiodine treatment applying 2 GBq {sup 131}I. Ten animals received 200 mg/kg amifostine prior to high-dose radioiodine therapy, and 5 served as controls. Salivary glands were examined histopathologically. Results: Variation coefficient of parenchymal function was less than 3.8% in salivary glands. Prior to HDRIT, thyroid uptake was 0.417 {+-} 0.373% and 0.421 {+-} 0.241% in control and amifostine-treated rabbits, respectively. Four weeks after HDRIT, complete ablation of the thyroid was achieved in both groups. Prior to HDRIT, uptake of {sup 99m}Tc-pertechnetate in salivary glands of five control rabbits was not significantly different from ten amifostine-treated rabbits. In control rabbits 6 months after HDRIT, parenchymal function was reduced significantly (p < 0.0001) by 75.3 {+-} 5.3% and 53.6 {+-} 17.4% in parotid and submandibular glands, respectively. In contrast, in amifostine-treated rabbits, parenchymal function was reduced by 10.6 {+-} 3.4% and 6.5 {+-} 4.3% (p > 0.05) in parotid and submandibular glands, respectively. Histopathologically, marked lipomatosis was observed in control animals but was negligible in amifostine-treated animals. Conclusion

A hyperoxic lung injury model in premature rabbits: the influence of different gestational ages and oxygen concentrations.

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Roberta Munhoz Manzano

Full Text Available BACKGROUND: Many animal models have been developed to study bronchopulmonary dysplasia (BPD. The preterm rabbit is a low-cost, easy-to-handle model, but it has a high mortality rate in response to the high oxygen concentrations used to induce lung injury. The aim of this study was to compare the mortality rates of two models of hyperoxia-induced lung injury in preterm rabbits. METHODS: Pregnant New Zealand white rabbits were subjected to caesarean section on gestational day 28 or 29 (full term  = 31 days. The premature rabbits in the 28-day gestation group were exposed to room air or FiO₂ ≥95%, and the rabbits in the 29-day gestation group were exposed to room air or FiO₂  = 80% for 11 days. The mean linear intercept (Lm, internal surface area (ISA, number of alveoli, septal thickness and proportion of elastic and collagen fibers were quantified. RESULTS: The survival rates in the 29-day groups were improved compared with the 28-day groups. Hyperoxia impaired the normal development of the lung, as demonstrated by an increase in the Lm, the septal thickness and the proportion of elastic fibers. Hyperoxia also decreased the ISA, the number of alveoli and the proportion of collagen fibers in the 28-day oxygen-exposed group compared with the control 28-day group. A reduced number of alveoli was found in the 29-day oxygen exposed animals compared with the control 29-day group. CONCLUSIONS: The 29-day preterm rabbits had a reduced mortality rate compared with the 28-day preterm rabbits and maintained a reduction in the alveoli number, which is comparable to BPD in humans.

Solvent/Detergent Virally Inactivated Serum Eye Drops Restore Healthy Ocular Epithelium in a Rabbit Model of Dry-Eye Syndrome.

Science.gov (United States)

Tseng, Ching-Li; Chen, Zhi-Yu; Renn, Ting-Yi; Hsiao, Shun-Hung; Burnouf, Thierry

2016-01-01

Application of autologous serum eye drops (SEDs) is a recognized means to treat severe dry-eye syndrome (DES). Due to the inconvenience and difficulty of preparing SEDs from some patients, producing SEDs from allogeneic blood donations is gaining popularity. A major safety concern associated with allogeneic blood is virus transmission. We therefore herein evaluated the possibility of applying a solvent/detergent (S/D) treatment to inactivate viruses and studied the impacts of such treatment of SEDs to resolve DES in a rabbit model. Sera prepared from the blood of five rabbits were pooled and divided into two sub-pools. One was untreated (SEDs), while the other was virally-inactivated with 1% Tri-n-butyl phosphate/1% Triton X-45 at 31°C for 1 h (S/D-SEDs). DES was induced in rabbits using 0.1% benzalkonium chloride (BAC). Rabbits were divided into five groups of two rabbits each. One group was untreated (control), three were treated twice daily for 3 weeks using PBS, SEDs, or S/D-SEDs, and the last received an additional 0.1% BAC (as the negative control). The DES condition was determined by measuring aqueous tear secretion (Schirmer's test), corneal fluorescein staining, a corneal histologic examination, TUNEL stain apoptosis, and corneal inflammatory marker (tumor necrosis factor-α, interleukin (IL)-1β, IL-8, and IL-6) expressions. We first confirmed that SEDs and S/D-SEDs had similar protein profiles and transforming growth factor (TGF)-β contents. Animal experiments showed that tear secretion did not significantly differ between the SED and S/D-SED groups but was significantly higher than in the PBS group. Eye fluorescein staining revealed dramatic improvements in epithelial defects in groups treated with SEDs or S/D-SEDs, and hematoxylin/eosin staining revealed microscopic epithelial layers similar to those of the untreated controls. Inflammatory markers and TUNEL studies showed that healthy epithelium had been restored in groups treated with SEDs or S

Stochastic models for tumoral growth

Science.gov (United States)

Escudero, Carlos

2006-02-01

Strong experimental evidence has indicated that tumor growth belongs to the molecular beam epitaxy universality class. This type of growth is characterized by the constraint of cell proliferation to the tumor border and the surface diffusion of cells at the growing edge. Tumor growth is thus conceived as a competition for space between the tumor and the host, and cell diffusion at the tumor border is an optimal strategy adopted for minimizing the pressure and helping tumor development. Two stochastic partial differential equations are reported in this paper in order to correctly model the physical properties of tumoral growth in (1+1) and (2+1) dimensions. The advantage of these models is that they reproduce the correct geometry of the tumor and are defined in terms of polar variables. An analysis of these models allows us to quantitatively estimate the response of the tumor to an unfavorable perturbation during growth.

Atelocollagen Enhances the Healing of Rotator Cuff Tendon in Rabbit Model.

Science.gov (United States)

Suh, Dong-Sam; Lee, Jun-Keun; Yoo, Ji-Chul; Woo, Sang-Hun; Kim, Ga-Ram; Kim, Ju-Won; Choi, Nam-Yong; Kim, Yongdeok; Song, Hyun-Seok

2017-07-01

Failure of rotator cuff healing is a common complication despite the rapid development of surgical repair techniques for the torn rotator cuff. To verify the effect of atelocollagen on tendon-to-bone healing in the rabbit supraspinatus tendon compared with conventional cuff repair. Controlled laboratory study. A tear of the supraspinatus tendon was created and repaired in 46 New Zealand White rabbits. They were then randomly allocated into 2 groups (23 rabbits per group; 15 for histological and 8 for biomechanical test). In the experimental group, patch-type atelocollagen was implanted between bone and tendon during repair; in the control group, the torn tendon was repaired without atelocollagen. Each opposite shoulder served as a sham (tendon was exposed only). Histological evaluation was performed at 4, 8, and 12 weeks. Biomechanical tensile strength was tested 12 weeks after surgery. Histological evaluation scores of the experimental group (4.0 ± 1.0) were significantly superior to those of the control group (7.7 ± 2.7) at 12 weeks ( P = .005). The load to failure was significantly higher in the experimental group (51.4 ± 3.9 N) than in the control group (36.4 ± 5.9 N) ( P = .001). Histological and biomechanical studies demonstrated better results in the experimental group using atelocollagen in a rabbit model of the supraspinatus tendon tear. Atelocollagen patch could be used in the cuff repair site to enhance healing.

Ultrasonographic analysis versus histopathologic evaluation of carotid advanced atherosclerotic stenosis in an experimental rabbit model.

Science.gov (United States)

Mehrad, Hossein; Mokhtari-Dizaji, Manijhe; Ghanaati, Hossein; Shahbazfar, Amir-Ali; Salehnia, Mojdeh

2012-08-01

Advanced carotid atherosclerosis with severe stenosis (>70%) is a major clinical risk factor for ischemic stroke. Our ability to test new protocols for the treatment of atherosclerotic stenosis in humans is limited for obvious ethical reasons; therefore, a suitable animal model is required. The aim of this study was to generate an easily reproducible and inexpensive experimental rabbit carotid model of advanced atherosclerosis with morphological similarities to the human disease and the subsequent assessment of the reliability of B-mode ultrasound technology in the study of lumen area stenosis in this model. Briefly, New Zealand white rabbits underwent primary perivascular cold injury at the right common carotid artery followed by a 1.5% cholesterol-rich diet injury for eight weeks. All of the rabbits' arteries were imaged by B-mode ultrasound weekly, after which the rabbits were sacrificed, and their vessels were processed for histopathology. Ultrasound longitudinal view images from three cardiac cycles were processed by a new computerized analyzing method based on dynamic programming and maximum gradient algorithm for measurement of instantaneous changes in arterial wall thickness and lumen diameter in sequential ultrasound images. Histopathology results showed progressive changes, from the lipid-laden cells and fibrous connective tissue proliferation in neointimal layer, up to the fibro-lipid plaque formation, resulting in vessel wall thickening, remodeling and lumen stenosis. The B-mode ultrasound images and the histologic measurements showed an increase in the mean wall thickness and the lumen area stenosis within eight weeks. Quantitative and morphometric analysis of the mean wall thickness and the lumen area stenosis percentage showed a significant correlation between the B-mode ultrasound and the histological measurements at each time point (R = 0.989 and R = 0.995, p < 0.05, respectively). In conclusion, we successfully produced advanced atherosclerosis in

Effects of a topical hemostatic agent on an epistaxis model in rabbits.

Science.gov (United States)

Kurtaran, Hanifi; Ark, Nebil; Serife Ugur, K; Sert, Huseyin; Ozboduroglu, Akin Altug; Kosar, Ali; Gunduz, Mehmet

2010-04-01

Ankaferd BloodStopper (ABS) is a standardized herbal compound consisting of 5 different plant extracts. ABS, as a topical medicinal product, has been approved by the Turkish Ministry of Health for the management of dermal, external postsurgical and postdental surgery bleedings. The aim of this study was to assess the hemostatic effect of ABS in an experimental epistaxis model. Adult female New Zealand rabbits were used in this study. Standardized full-thickness mucosal wounds were created to provide bleeding on the right and left side of the nasal septum of rabbits with a 3-mm surgical punch. To stop bleeding, the wounds were treated with topical ABS on one side and with topical isotonic saline solution as a control on the other side of the nasal septum. Investigators were blinded to treatment. The duration of bleeding was measured in order to compare the hemo-static effect with ABS or topical isotonic saline solution. The wounds were observed for the duration of bleeding in order to compare the hemostatic effect of ABS with isotonic saline solution and acute adverse effects (AEs) for 30 minutes by a researcher blinded to treatment groups. Six rabbits (mean weight, 2.6 kg [range, 2.3-3.1 kg]) were used in this study. Mean (SD) bleeding time in the wounds administered ABS (98 [17] sec) was significantly less than that of the controls (266 [36] sec; P = 0.004). No AEs were observed up to 30 minutes after study initiation. This study suggests that ABS may be more effective in reducing time to hemostasis when compared with isotonic saline solution in this epistaxis model in rabbits.

A radioactive seed implant on a rabbit's liver following a voxel model representation for dosimetric proposals

Energy Technology Data Exchange (ETDEWEB)

Campos, Tarcisio P.R.; Andrade, Joao Paulo Lopes de; Costa, Igor Temponi; Teixeira, Cleuza H. [Minas Gerais Univ., Belo Horizonte, MG (Brazil). Programa de Pos-graduacao em Ciencias e Tecnicas Nucleares]. E-mail: campos@nuclear.ufmg

2005-07-01

Animal models have been used in experimentation with ionizing radiation. The evaluation of the energy absorbed per unit tissue mass in vivo transported by nuclear particles is a task to be performed before experimentation. Stochastic or deterministic methodology can be applied, however the dosimetric protocols applied in radiotherapy center cannot be applied directly due to the inherent small geometry and chemical composition of the animal distinct from human. The present article addresses a method in development that will predict the dose distribution into the rabbit thorax based on the solution of the transport phenomena in a voxel model. The model will be applied to simulate a seed implant experiment on a rabbit. Herein, the construction of the three-dimensional voxel model anthropomorphic -anthropometrics to the rabbit is presented. The model is assembling from a set of computer tomography of the rabbit. The computational phantom of the thorax starts at the digitalisation of the CT images, tissue definition, and color image representation of each tissue and organ. The chemical composition and mass density of each tissue is evaluated as similar date presented by ICRU-44. To treat the images, a code namely SISCODES, developed in house, was used. The in vivo experiment that will be simulated is also described. That is a implant of five seeds of 1.6x2 mm performed in a rabbit's liver. The perspective of this work is the application of the model in dosimetric studies predicting the dose distribution around the seed's implanted in vivo experiments. (author)

Development of 68Ga-Glycopeptide as an Imaging Probe for Tumor Angiogenesis

Directory of Open Access Journals (Sweden)

Ning Tsao

2011-01-01

Full Text Available Objective. This study was aimed to study tissue distribution and tumor imaging potential of 68Ga-glycopeptide (GP in tumor-bearing rodents by PET. Methods. GP was synthesized by conjugating glutamate peptide and chitosan. GP was labeled with 68Ga chloride for in vitro and in vivo studies. Computer outlined region of interest (counts per pixel of the tumor and muscle (at the symmetric site was used to determine tumor-to-muscle count density ratios. To ascertain the feasibility of 68Ga-GP in tumor imaging in large animals, PET/CT imaging of 68Ga-GP and 18F-FDG were conducted in New Zealand white rabbits bearing VX2 tumors. Standard uptake value of tumors were determined by PET up to 45 min. To determine blood clearance and half-life of 68Ga-GP, blood samples were collected from 10 seconds to 20 min. Results. Radiochemical purity of 68Ga-GP determined by instant thin-layer chromatography was >95%. Tumor uptake values (SUV for 68Ga-GP and 18F-FDG in New Zealand white rabbits bearing VX2 tumors were 3.25 versus 7.04. PET images in tumor-bearing rats and rabbits confirmed that 68Ga-GP could assess tumor uptake. From blood clearance curve, the half-life of 68Ga-GP was 1.84 hr. Conclusion Our data indicate that it is feasible to use 68Ga-GP to assess tumor angiogenesis.

[The effect of portal blood stasis on lung and renal injury induced by hepatic ischemia reperfusion in a rabbit model].

Science.gov (United States)

Wang, Ye; Yang, Jia-mei; Hou, Yuan-kai; Li, Dian-qi; Hu, Ming-hua; Liu, Peng

2008-04-15

To investigate the effect and mechanism of portal blood stasis on lung and renal injury induced by hepatic ischemia reperfusion. A rabbit hepatic ischemia reperfusion injury model was established by hepatic portal occlusion and in situ hypothermic irrigation for 30 min. Twenty-four New Zealand white rabbits were employed and randomly divided into 3 groups equally by different dosage of portal blood stasis removal: group A5 (5 ml blood removal), group A10 (10 ml blood removal),and group B (no blood removal). Eight rabbits were served as controls with no hepatic portal occlusion and hypothermic irrigation. After reperfusion 4 h serum endotoxin content, tumor necrosis factor-alpha (TNF-alpha), urea nitrogen (BUN), and creatinine (Cr) were examined respectively, meantime lung and kidney tissues were sampled to determine the content of malondialdehyde (MDA), superoxide dismutase (SOD), the pathology, and wet to dry weight ratio, broncho-alveolar lavage fluid protein content in lung tissues. Removing portal blood stasis ameliorated lung and renal injury as shown by decreasing the level of serum endotoxin, TNF-alpha, BUN, Cr, wet to dry weight ratio, broncho-alveolar lavage fluid protein content, MDA, SOD. TNF-alpha, Cr, broncho-alveolar lavage fluid protein content in lung tissues and MDA in kidney tissue in group A5 were significantly reduced compared with those in group B (P portal blood stasis before the resume of splanchnic circulation may ameliorate the lung and renal injury induced by hepatic ischemia reperfusion. The possible mechanism may be that portal blood stasis removal reduces endotoxin absorption, and further decreases production of serum TNF-alpha.

Use of routine clinical multimodality imaging in a rabbit model of osteoarthritis--part I.

Science.gov (United States)

Bouchgua, M; Alexander, K; d'Anjou, M André; Girard, C A; Carmel, E Norman; Beauchamp, G; Richard, H; Laverty, S

2009-02-01

To evaluate in vivo the evolution of osteoarthritis (OA) lesions temporally in a rabbit model of OA with clinically available imaging modalities: computed radiography (CR), helical single-slice computed tomography (CT), and 1.5 tesla (T) magnetic resonance imaging (MRI). Imaging was performed on knees of anesthetized rabbits [10 anterior cruciate ligament transection (ACLT) and contralateral sham joints and six control rabbits] at baseline and at intervals up to 12 weeks post-surgery. Osteophytosis, subchondral bone sclerosis, bone marrow lesions (BMLs), femoropatellar effusion and articular cartilage were assessed. CT had the highest sensitivity (90%) and specificity (91%) to detect osteophytes. A significant increase in total joint osteophyte score occurred at all time-points post-operatively in the ACLT group alone. BMLs were identified and occurred most commonly in the lateral femoral condyle of the ACLT joints and were not identified in the tibia. A significant increase in joint effusion was present in the ACLT joints until 8 weeks after surgery. Bone sclerosis or cartilage defects were not reliably assessed with the selected imaging modalities. Combined, clinically available CT and 1.5 T MRI allowed the assessment of most of the characteristic lesions of OA and at early time-points in the development of the disease. However, the selected 1.5 T MRI sequences and acquisition times did not permit the detection of cartilage lesions in this rabbit OA model.

Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques.

Science.gov (United States)

Borggren, Marie; Vinner, Lasse; Andresen, Betina Skovgaard; Grevstad, Berit; Repits, Johanna; Melchers, Mark; Elvang, Tara Laura; Sanders, Rogier W; Martinon, Frédéric; Dereuddre-Bosquet, Nathalie; Bowles, Emma Joanne; Stewart-Jones, Guillaume; Biswas, Priscilla; Scarlatti, Gabriella; Jansson, Marianne; Heyndrickx, Leo; Grand, Roger Le; Fomsgaard, Anders

2013-07-19

HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies (bNAb). We compared three different animal models: guinea pigs, rabbits and cynomolgus macaques. Envelope genes from the prototype isolate HIV-1 Bx08 and two elite neutralizers were included. Codon-optimized genes, encoded secreted gp140 or membrane bound gp150, were modified for expression of stabilized soluble trimer gene products, and delivered individually or mixed. Specific IgG after repeated i.d. inoculations with electroporation confirmed in vivo expression and immunogenicity. Evaluations of rabbits and guinea pigs displayed similar results. The superior DNA construct in rabbits was a trivalent mix of non-modified codon-optimized gp140 envelope genes. Despite NAb responses with some potency and breadth in guinea pigs and rabbits, the DNA vaccinated macaques displayed less bNAb activity. It was concluded that a trivalent mix of non-modified gp140 genes from rationally selected clinical isolates was, in this study, the best option to induce high and broad NAb in the rabbit model, but this optimization does not directly translate into similar responses in cynomolgus macaques.

Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques

Directory of Open Access Journals (Sweden)

Roger Le Grand

2013-07-01

Full Text Available HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies (bNAb. We compared three different animal models: guinea pigs, rabbits and cynomolgus macaques. Envelope genes from the prototype isolate HIV-1 Bx08 and two elite neutralizers were included. Codon-optimized genes, encoded secreted gp140 or membrane bound gp150, were modified for expression of stabilized soluble trimer gene products, and delivered individually or mixed. Specific IgG after repeated i.d. inoculations with electroporation confirmed in vivo expression and immunogenicity. Evaluations of rabbits and guinea pigs displayed similar results. The superior DNA construct in rabbits was a trivalent mix of non-modified codon-optimized gp140 envelope genes. Despite NAb responses with some potency and breadth in guinea pigs and rabbits, the DNA vaccinated macaques displayed less bNAb activity. It was concluded that a trivalent mix of non-modified gp140 genes from rationally selected clinical isolates was, in this study, the best option to induce high and broad NAb in the rabbit model, but this optimization does not directly translate into similar responses in cynomolgus macaques.

Development of a modified model of spinal cord ischemia injury by selective ligation of lumbar arteries in rabbits.

Science.gov (United States)

Xiao, W; Wen, J; Huang, Y-C; Yu, B-S

2017-11-01

Experimental study. The aim of this study is to develop a modified model of spinal cord ischemia in rabbits. Shenzhen Key Laboratory of Spine Surgery, Shenzhen, China. In total, 20 New Zealand rabbits were divided into the following four groups according to the level of ligation of bilateral lumbar arteries: (1) group A, sham group, no ligation, n=5; (2) group B, ligation of bilateral lumbar arteries at three levels (L2-L4, n=5); (3) group C, ligation of bilateral lumbar arteries at four levels (L2-L5, n=5); and (4) group D, ligation of bilateral lumbar arteries at five levels (L1-L5, n=5). The latency of motor-evoked potentials was measured intraoperatively and the modified Tarlov grades were scored, followed by a histological observation of spinal cord, on the seventh day after surgery. All 10 rabbits in Group A and Group B were electrophysiologically, neurologically and histologically normal. In Group C, moderate spinal cord ischemia injury was found in three of five rabbits: they had prolonged latency of motor-evoked potentials and neuronal karyopyknosis in the anterior horn of spinal cord, and the average Tarlov score was 4.2±0.8. In Group D, severe spinal cord ischemia injury was recorded in all the five rabbits: the latency of motor-evoked potential prolonged in one rabbit, whereas the waveform disappeared in four rabbits; loss of neurons and vacuolation of gray matter were seen in spinal cord sections, and the average Tarlov score was 0.6±0.9. Selective ligation of lumbar arteries was a modified method to induce feasible and reproducible model of spinal cord ischemia in rabbits.

Acute lung injury and persistent small airway disease in a rabbit model of chlorine inhalation

Energy Technology Data Exchange (ETDEWEB)

Musah, Sadiatu; Schlueter, Connie F.; Humphrey, David M. [Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY (United States); Powell, Karen S. [Research Resource Facilities, University of Louisville, Louisville, KY (United States); Roberts, Andrew M. [Department of Physiology, University of Louisville, Louisville, KY (United States); Hoyle, Gary W., E-mail: Gary.Hoyle@louisville.edu [Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY (United States)

2017-01-15

Chlorine is a pulmonary toxicant to which humans can be exposed through accidents or intentional releases. Acute effects of chlorine inhalation in humans and animal models have been well characterized, but less is known about persistent effects of acute, high-level chlorine exposures. In particular, animal models that reproduce the long-term effects suggested to occur in humans are lacking. Here, we report the development of a rabbit model in which both acute and persistent effects of chlorine inhalation can be assessed. Male New Zealand White rabbits were exposed to chlorine while the lungs were mechanically ventilated. After chlorine exposure, the rabbits were extubated and were allowed to survive for up to 24 h after exposure to 800 ppm chlorine for 4 min to study acute effects or up to 7 days after exposure to 400 ppm for 8 min to study longer term effects. Acute effects observed 6 or 24 h after inhalation of 800 ppm chlorine for 4 min included hypoxemia, pulmonary edema, airway epithelial injury, inflammation, altered baseline lung mechanics, and airway hyperreactivity to inhaled methacholine. Seven days after recovery from inhalation of 400 ppm chlorine for 8 min, rabbits exhibited mild hypoxemia, increased area of pressure–volume loops, and airway hyperreactivity. Lung histology 7 days after chlorine exposure revealed abnormalities in the small airways, including inflammation and sporadic bronchiolitis obliterans lesions. Immunostaining showed a paucity of club and ciliated cells in the epithelium at these sites. These results suggest that small airway disease may be an important component of persistent respiratory abnormalities that occur following acute chlorine exposure. This non-rodent chlorine exposure model should prove useful for studying persistent effects of acute chlorine exposure and for assessing efficacy of countermeasures for chlorine-induced lung injury. - Highlights: • A novel rabbit model of chlorine-induced lung disease was developed. �

Effects of head down tilt on episcleral venous pressure in a rabbit model.

Science.gov (United States)

Lavery, W J; Kiel, J W

2013-06-01

In humans, changing from upright to supine elicits an approximately 10 mmHg increase in cephalic venous pressure caused by the hydrostatic column effect, but episcleral venous pressure (EVP) and intraocular pressure (IOP) rise by only a few mmHg. The dissociation of the small increases in IOP and EVP compared to the larger increase in cephalic venous pressure suggests a regulatory mechanism controlling EVP. The aim of the present study was to determine if the rabbit model is suitable to study the effects of postural changes on EVP despite its short hydrostatic column. In anesthetized rabbits (n = 43), we measured arterial pressure (AP), IOP, and orbital venous pressure (OVP) by direct cannulation; carotid blood flow (BFcar) by transit time ultrasound, heart rate (HR) by digital cardiotachometer, and EVP with a servonull micropressure system. The goal of the protocol was to obtain measurement of supine EVP for ≈10 min, followed by ≈10 min of EVP measurement with the rabbit in a head down tilt. The data were analyzed by paired t-tests and the results reported as the mean ± standard error of the mean. In a separate group of animals (n = 35), aqueous flow was measured by fluorophotometry. This protocol entailed measurement of aqueous flow in the supine position for ≈60 min, followed by ≈60 min of aqueous flow measurement with the rabbit in a head down tilt. From supine to head down tilt, AP and BFcar were unchanged, IOP increased by 2.3 ± 0.4 mmHg (p measurements of the pressures and systemic parameters likely involved in the EVP responses to posture change. The present results indicate directionally similar EVP and IOP responses to tilt as occur in humans and, as in humans, the responses are smaller than would be expected from the change in the hydrostatic column height. Also, as in humans, the model reveals no change in aqueous flow during head down tilt. We conclude the rabbit model is appropriate for studying the mechanisms responsible for the relative

Joint distraction and movement for repair of articular cartilage in a rabbit model with subsequent weight-bearing.

Science.gov (United States)

Nishino, T; Chang, F; Ishii, T; Yanai, T; Mishima, H; Ochiai, N

2010-07-01

We have previously shown that joint distraction and movement with a hinged external fixation device for 12 weeks was useful for repairing a large articular cartilage defect in a rabbit model. We have now investigated the results after six months and one year. The device was applied to 16 rabbits who underwent resection of the articular cartilage and subchondral bone from the entire tibial plateau. In group A (nine rabbits) the device was applied for six months. In group B (seven rabbits) it was in place for six months, after which it was removed and the animals were allowed to move freely for an additional six months. The cartilage remained sound in all rabbits. The areas of type II collagen-positive staining and repaired soft tissue were larger in group B than in group A. These findings provide evidence of long-term persistence of repaired cartilage with this technique and that weight-bearing has a positive effect on the quality of the cartilage.

Biodegradable urethral stent in the treatment of post-traumatic urethral strictures in a war wound rabbit urethral model

International Nuclear Information System (INIS)

Fu Weijun; Zhang Binghong; Gao Jiangping; Hong Baofa; Zhang Lei; Yang Yong; Meng Bo; Zhu Ning; Cui Fuzhai

2007-01-01

To prevent terrorism during anti-terror war, we developed a reproducible animal model for the induction of a urethral stricture in a war wound rabbit, and to evaluate the feasibility and effect of using a biodegradable urethral stent in the prophylaxis and treatment of urethral strictures in a war wound (or traumatic) rabbit urethral model. The urethral stricture rabbit model was successfully performed by a self-control explosion destructor. New biodegradable urethral stents were placed in the urethras of 20 war wound (traumatic) rabbits, but no stent was used in the 8 rabbits which formed the control group. Follow-up investigation included assessment of procedure success, stent changes, urethrascopy and retrograde urethrography, and histological findings were obtained after sacrifice at 4, 6, 8 and 12 weeks after stent placement. The urethral stricture model owing to a war wound (trauma) was tested by tissue reactions and urethroscopy. The length of the urethral strictures was 5-10 mm; the coarctatetion of the urethral lumen was more than 50%. Biodegradable stent placement was technically successful in 20 rabbits. Urethral specimens obtained from the 4 week stent placement group showed diminished inflammatory cell infiltration and decreased thickness of the papillary projections of the epithelium. There was a strong tendency towards regression of the papillary projections and regeneration of urethral mucosa epithelium in the 8 week group. In particular, the injured urethra has recovered completely in the biodegradable stent groups compared with the control group at 12 weeks. The biodegradable urethral stent seems feasible for treating and preventing urethral strictures owing to a war wound (or traumatic) urethra. There are distinct advantages in terms of safe, effective and less-invasive treatment for the reconstruction of post-traumatic urethral strictures

Biodegradable urethral stent in the treatment of post-traumatic urethral strictures in a war wound rabbit urethral model

Energy Technology Data Exchange (ETDEWEB)

Fu Weijun [Department of Urology, Chinese People' s Liberation Army General Hospital, Military Postgraduate Medical College, No.28 Fuxing Road, Hai dian District, Beijing 100853 (China); Zhang Binghong [Department of Urology, Chinese People' s Liberation Army General Hospital, Military Postgraduate Medical College, No.28 Fuxing Road, Hai dian District, Beijing 100853 (China); Gao Jiangping [Department of Urology, Chinese People' s Liberation Army General Hospital, Military Postgraduate Medical College, No.28 Fuxing Road, Hai dian District, Beijing 100853 (China); Hong Baofa [Department of Urology, Chinese People' s Liberation Army General Hospital, Military Postgraduate Medical College, No.28 Fuxing Road, Hai dian District, Beijing 100853 (China); Zhang Lei [Department of Urology, Chinese People' s Liberation Army General Hospital, Military Postgraduate Medical College, No.28 Fuxing Road, Hai dian District, Beijing 100853 (China); Yang Yong [Department of Urology, Chinese People' s Liberation Army General Hospital, Military Postgraduate Medical College, No.28 Fuxing Road, Hai dian District, Beijing 100853 (China); Meng Bo [Biomaterials Lab, School of Materials Science and Engineering, Tsinghua University, Beijing (China); Zhu Ning [Biomaterials Lab, School of Materials Science and Engineering, Tsinghua University, Beijing (China); Cui Fuzhai [Biomaterials Lab, School of Materials Science and Engineering, Tsinghua University, Beijing (China)

2007-12-15

To prevent terrorism during anti-terror war, we developed a reproducible animal model for the induction of a urethral stricture in a war wound rabbit, and to evaluate the feasibility and effect of using a biodegradable urethral stent in the prophylaxis and treatment of urethral strictures in a war wound (or traumatic) rabbit urethral model. The urethral stricture rabbit model was successfully performed by a self-control explosion destructor. New biodegradable urethral stents were placed in the urethras of 20 war wound (traumatic) rabbits, but no stent was used in the 8 rabbits which formed the control group. Follow-up investigation included assessment of procedure success, stent changes, urethrascopy and retrograde urethrography, and histological findings were obtained after sacrifice at 4, 6, 8 and 12 weeks after stent placement. The urethral stricture model owing to a war wound (trauma) was tested by tissue reactions and urethroscopy. The length of the urethral strictures was 5-10 mm; the coarctatetion of the urethral lumen was more than 50%. Biodegradable stent placement was technically successful in 20 rabbits. Urethral specimens obtained from the 4 week stent placement group showed diminished inflammatory cell infiltration and decreased thickness of the papillary projections of the epithelium. There was a strong tendency towards regression of the papillary projections and regeneration of urethral mucosa epithelium in the 8 week group. In particular, the injured urethra has recovered completely in the biodegradable stent groups compared with the control group at 12 weeks. The biodegradable urethral stent seems feasible for treating and preventing urethral strictures owing to a war wound (or traumatic) urethra. There are distinct advantages in terms of safe, effective and less-invasive treatment for the reconstruction of post-traumatic urethral strictures.

Experimental rat lung tumor model with intrabronchial tumor cell implantation.

Science.gov (United States)

Gomes Neto, Antero; Simão, Antônio Felipe Leite; Miranda, Samuel de Paula; Mourão, Lívia Talita Cajaseiras; Bezerra, Nilfácio Prado; Almeida, Paulo Roberto Carvalho de; Ribeiro, Ronaldo de Albuquerque

2008-01-01

The objective of this study was to develop a rat lung tumor model for anticancer drug testing. Sixty-two female Wistar rats weighing 208 +/- 20 g were anesthetized intraperitoneally with 2.5% tribromoethanol (1 ml/100 g live weight), tracheotomized and intubated with an ultrafine catheter for inoculation with Walker's tumor cells. In the first step of the experiment, a technique was established for intrabronchial implantation of 10(5) to 5 x 10(5) tumor cells, and the tumor take rate was determined. The second stage consisted of determining tumor volume, correlating findings from high-resolution computed tomography (HRCT) with findings from necropsia and determining time of survival. The tumor take rate was 94.7% for implants with 4 x 10(5) tumor cells, HRCT and necropsia findings matched closely (r=0.953; p<0.0001), the median time of survival was 11 days, and surgical mortality was 4.8%. The present rat lung tumor model was shown to be feasible: the take rate was high, surgical mortality was negligible and the procedure was simple to perform and easily reproduced. HRCT was found to be a highly accurate tool for tumor diagnosis, localization and measurement and may be recommended for monitoring tumor growth in this model.

An animal model of necrotizing enterocolitis (NEC) in preterm rabbits.

Science.gov (United States)

Bozeman, Andrew P; Dassinger, Melvin S; Birusingh, Rhea J; Burford, Jeffrey M; Smith, Samuel D

2013-04-01

Creation of an animal model of necrotizing enterocolitis (NEC) allowing adjustment of severity and potential recoverability is needed to study effectiveness of prevention and treatment strategies. This study describes a novel model in preterm rabbits capable of adjusting severity of NEC-like histologic changes. Rabbit pups (n = 151) were delivered by cesarean section 2 days preterm. In the treatment groups, tissue adhesive was applied to anal openings to simulate the poor intestinal function and dysmotility of preterm neonates. Pups were placed into five groups: 3INT (3 day intermittent block), 4INT (4 day intermittent block), 3COM (3 day complete block), 4COM (4 day complete block), based on differences in type of anal blockage and day of life sacrificed. The fifth group, 4CON, was comprised of a control arm (n = 28) without anal block, with sacrifice of subjects on day 4. All pups were gavage fed with formula contaminated with Enterobacter cloacae, ranitidine, and indomethacin. Following sacrifice, the intestines were harvested for pathologic evidence of NEC. A blinded pathologist graded histologic changes consistent with NEC using a grading scale 0-4 with 4 being most severe. Fifty-seven pups (57/123) (46%) in the research arm survived to sacrifice, compared to 26/28 (93%) in the control arm of the investigation, p < 0.0001. The incidence and severity of NEC-like damage increased with the duration and completeness of the anal blockage. 44/57 (77%) of survivors revealed various degrees of NEC-like damage to large and small bowel, and 3/26 (12%) exhibited early NEC-like mucosal injury in the research and control arms, respectively. This animal model produces NEC-like pathologic changes in both small and large intestine in preterm rabbits. Because incidence and severity of damage increases with duration and completeness of intestinal dysmotility, this allows future effectiveness studies for nonsurgical treatment and prevention of NEC.

Dosimetric response of radioactive bio glass seeds implants on rabbit brain; Resposta radiodosimetrica de implantes de sementes de biovidros radioativos no cerebro de coelhos

Energy Technology Data Exchange (ETDEWEB)

Costa, I.T.; Campos, T.P.R., E-mail: itemponi@yahoo.com.br, E-mail: campos@nuclear.ufmg.br [Programa de Pos-Graduacao em Ciencias e Tecnicas Nucleares - Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil)

2007-07-01

Interstitial implants of radioactive seeds are used as an efficient way of treating brain tumors. Bio glasses is an interesting alternative to the metallic implanted materials, because they can be absorbed by the organism, reducing the possibilities of side effects. The present paper investigates the dosimetry by the implants performed on rabbit's brain on the NRI/UFMG research group. The spatial distribution of the specific ionizing energy deposited per unit of mass generated by Sm-153 seeds were evaluated. A computational model of the brain's region was built using the software SISCODES produced by the research group. The sections of the computer tomography of a rabbit, which was included on the experiment, were digitalized. Those were converted in a three dimensional voxel model, including the tissues, its chemical composition and density. A simulation of the particles transport is performed by the stochastic code MCNP5. The implants consist of 15 ceramic Ca-Si-Sm seeds enriched with Sm-153, with 1.1.6 mm of length and 0.3 mm diameter, implanted on the rabbit's brain. It was predicted on the model three ribbons of 5 seeds each, spaced by 1.1.2 mm, since the ribbons were in a triangular topology whose vertices were spaced by 8 mm. The activities were 120 MBq/seed. The results show isodose regions superposed over the rabbits' model, reproducing the spatial energy deposition on the brain region. The absorbed dose predicted was 3.2 Gy per 15 seed; however it was not enough to tumor control. The authors suggest to increase the number of seeds and activity, reduction of the space to 5-6 mm among ribbons, improving dose with the beta emitting. (author)

Technique Development Results for the Study of a Novel Dexamethasone Impregnated Bandage Contact Lens in a Rabbit Model After Photorefractive Keratectomy

Science.gov (United States)

2017-10-22

PRK Inflammation in a Rabbit Model Timothy A. Soekenl, Michael Merkley!, Wesley Brundridgel, Gary Legaultl, Matthew Caldwelll, Joseph Ciolino2...7 .0 Dexamethasone Impregnated Contact Lenses in the Treatment of Post- PRK Inflammation · in a Rabbit Model Timothy A. Soeken 1, Michael Merkley1

Age related changes in tumor vascularity

International Nuclear Information System (INIS)

Loerelius, L.E.; Stridbeck, H.

1984-01-01

VX 2 tumors in the rabbit hind leg were investigated at one, two and three weeks of age. Angiograms were compared with vascular casts. The tumors grew rapidly the first two weeks of age. Large variations in vascularity were noted between tumors of different ages. With increasing age arteriovenous shunts at the tumor periphery and areas of avascularity of necrosis in the tumor center increased in size. Possible reasons for tumor necrosis are increased tissue pressure, anoxia caused by arteriovenous shunts and elevation in venous pressure. The natural history of the VX 2 tumor must be considered in every experimental study of the effect of any treatment. (orig.)

Trichostatin A (TSA) improves the development of rabbit-rabbit intraspecies cloned embryos, but not rabbit-human interspecies cloned embryos.

Science.gov (United States)

Shi, Li-Hong; Miao, Yi-Liang; Ouyang, Ying-Chun; Huang, Jun-Cheng; Lei, Zi-Li; Yang, Ji-Wen; Han, Zhi-Ming; Song, Xiang-Fen; Sun, Qing-Yuan; Chen, Da-Yuan

2008-03-01

The interspecies somatic cell nuclear transfer (iSCNT) technique for therapeutic cloning gives great promise for treatment of many human diseases. However, the incomplete nuclear reprogramming and the low blastocyst rate of iSCNT are still big problems. Herein, we observed the effect of TSA on the development of rabbit-rabbit intraspecies and rabbit-human interspecies cloned embryos. After treatment with TSA for 6 hr during activation, we found that the blastocyst rate of rabbit-rabbit cloned embryos was more than two times higher than that of untreated embryos; however, the blastocyst rate of TSA-treated rabbit-human interspecies cloned embryos decreased. We also found evident time-dependent histone deacetylation-reacetylation changes in rabbit-rabbit cloned embryos, but not in rabbit-human cloned embryos from fusion to 6 hr after activation. Our results suggest that TSA-treatment does not improve blastocyst development of rabbit-human iSCNT embryos and that abnormal histone deacetylation-reacetylation changes in iSCNT embryos may account for their poor blastocyst development. (c) 2008 Wiley-Liss, Inc.

Hepatitis E Virus in Farmed Rabbits, Wild Rabbits and Petting Farm Rabbits in the Netherlands

NARCIS (Netherlands)

Burt, S.A.; Veltman, Jorg; Hakze-van der Honing, Renate; Schmitt, Heike; van der Poel, Wim H.M.

2016-01-01

Rabbits have been suggested as a zoonotic source of Hepatitis E virus. Phylogenetic analysis of HEV isolates from farmed, wild and pet rabbits in the Netherlands (23, 0, and 60 % respectively) showed them to be grouped amongst published rabbit HEV sequences and distinct from most human isolates.

Development of a rabbit's urethral sphincter deficiency animal model for anatomical-functional evaluation

Directory of Open Access Journals (Sweden)

M. Skaff

2012-02-01

Full Text Available OBJECTIVE: The aim of the study was to develop a new durable animal model (using rabbits for anatomical-functional evaluation of urethral sphincter deficiency. MATERIALS AND METHODS: A total of 40 New Zealand male rabbits, weighting 2.500 kg to 3.100 kg, were evaluated to develop an incontinent animal model. Thirty-two animals underwent urethrolysis and 8 animals received sham operation. Before and at 2, 4, 8 and 12 weeks after urethrolysis or sham operation, it was performed cystometry and leak point pressure (LPP evaluation with different bladder distension volumes (10, 20, 30 mL. In each time point, 10 animals (8 from the study group and 2 from the sham group were sacrificed to harvest the bladder and urethra. The samples were evaluated by H&E and Masson's Trichrome to determine urethral morphology and collagen/smooth muscle density. RESULTS: Twelve weeks after urethrolysis, it was observed a significant decrease in LPP regardless the bladder volume (from 33.7 ± 6.6 to 12.8 ± 2.2 cmH2O. The histological analysis evidenced a decrease of 22% in smooth muscle density with a proportional increase in the collagen, vessels and elastin density (p < 0.01. CONCLUSIONS: Transabdominal urethrolysis develops urethral sphincter insufficiency in rabbits, with significant decrease in LPP associated with decrease of smooth muscle fibers and increase of collagen density. This animal model can be used to test autologous cell therapy for stress urinary incontinence treatment.

Hepatitis E Virus in Farmed Rabbits, Wild Rabbits and Petting Farm Rabbits in the Netherlands

NARCIS (Netherlands)

Burt, Sara A.; Veltman, Jorg; Hakze-van der Honing, Renate; Schmitt, Heike; Poel, van der Wim H.M.

2016-01-01

Rabbits have been suggested as a zoonotic source of Hepatitis E virus. Phylogenetic analysis of HEV isolates from farmed, wild and pet rabbits in the Netherlands (23, 0, and 60 % respectively) showed them to be grouped amongst published rabbit HEV sequences and distinct from most human isolates.

Technetium-99m-labeled annexin V imaging for detecting prosthetic joint infection in a rabbit model.

Science.gov (United States)

Tang, Cheng; Wang, Feng; Hou, Yanjie; Lu, Shanshan; Tian, Wei; Xu, Yan; Jin, Chengzhe; Wang, Liming

2015-05-01

Accurate and timely diagnosis of prosthetic joint infection is essential to initiate early treatment and achieve a favorable outcome. In this study, we used a rabbit model to assess the feasibility of technetium-99m-labeled annexin V for detecting prosthetic joint infection. Right knee arthroplasty was performed on 24 New Zealand rabbits. After surgery, methicillin-susceptible Staphylococcus aureus was intra-articularly injected to create a model of prosthetic joint infection (the infected group, n = 12). Rabbits in the control group were injected with sterile saline (n = 12). Seven and 21 days after surgery, technetium-99m-labeled annexin V imaging was performed in 6 rabbits of each group. Images were acquired 1 and 4 hours after injection of technetium-99m-labeled annexin V (150 MBq). The operated-to-normal-knee activity ratios were calculated for quantitative analysis. Seven days after surgery, increased technetium-99m-labeled annexin V uptake was observed in all cases. However, at 21 days a notable decrease was found in the control group, but not in the infected group. The operated-to-normal-knee activity ratios of the infected group were 1.84 ± 0.29 in the early phase and 2.19 ± 0.34 in the delay phase, both of which were significantly higher than those of the control group (P = 0.03 and P = 0.02). The receiver operator characteristic curve analysis showed that the operated-to-normal-knee activity ratios of the delay phase at 21 days was the best indicator, with an accuracy of 80%. In conclusion, technetium-99m-labeled annexin V imaging could effectively distinguish an infected prosthetic joint from an uninfected prosthetic joint in a rabbit model.

Retinitis-pigmentosa-like tapetoretinal degeneration in a rabbit breed.

Science.gov (United States)

Reichenbach, A; Baar, U

1985-08-15

By chance, we found a rabbit strain with retinal dystrophy. The eyes of these rabbits were examined by ophthalmoscopy, electroretinography, histology, and cytology--the latter after retina dissociation with papaine. The results suggest this rabbit strain to be a possible animal model for human retinitis pigmentosa.

Tumor cell culture on collagen–chitosan scaffolds as three-dimensional tumor model: A suitable model for tumor studies

Directory of Open Access Journals (Sweden)

Aziz Mahmoudzadeh

2016-07-01

Full Text Available Tumor cells naturally live in three-dimensional (3D microenvironments, while common laboratory tests and evaluations are done in two-dimensional (2D plates. This study examined the impact of cultured 4T1 cancer cells in a 3D collagen–chitosan scaffold compared with 2D plate cultures. Collagen–chitosan scaffolds were provided and passed confirmatory tests. 4T1 tumor cells were cultured on scaffolds and then tumor cells growth rate, resistance to X-ray radiation, and cyclophosphamide as a chemotherapy drug were analyzed. Furthermore, 4T1 cells were extracted from the scaffold model and were injected into the mice. Tumor growth rate, survival rate, and systemic immune responses were evaluated. Our results showed that 4T1 cells infiltrated the scaffolds pores and constructed a 3D microenvironment. Furthermore, 3D cultured tumor cells showed a slower proliferation rate, increased levels of survival to the X-ray irradiation, and enhanced resistance to chemotherapy drugs in comparison with 2D plate cultures. Transfer of extracted cells to the mice caused enhanced tumor volume and decreased life span. This study indicated that collagen–chitosan nanoscaffolds provide a suitable model of tumor that would be appropriate for tumor studies.

Tumor cell culture on collagen-chitosan scaffolds as three-dimensional tumor model: A suitable model for tumor studies.

Science.gov (United States)

Mahmoudzadeh, Aziz; Mohammadpour, Hemn

2016-07-01

Tumor cells naturally live in three-dimensional (3D) microenvironments, while common laboratory tests and evaluations are done in two-dimensional (2D) plates. This study examined the impact of cultured 4T1 cancer cells in a 3D collagen-chitosan scaffold compared with 2D plate cultures. Collagen-chitosan scaffolds were provided and passed confirmatory tests. 4T1 tumor cells were cultured on scaffolds and then tumor cells growth rate, resistance to X-ray radiation, and cyclophosphamide as a chemotherapy drug were analyzed. Furthermore, 4T1 cells were extracted from the scaffold model and were injected into the mice. Tumor growth rate, survival rate, and systemic immune responses were evaluated. Our results showed that 4T1 cells infiltrated the scaffolds pores and constructed a 3D microenvironment. Furthermore, 3D cultured tumor cells showed a slower proliferation rate, increased levels of survival to the X-ray irradiation, and enhanced resistance to chemotherapy drugs in comparison with 2D plate cultures. Transfer of extracted cells to the mice caused enhanced tumor volume and decreased life span. This study indicated that collagen-chitosan nanoscaffolds provide a suitable model of tumor that would be appropriate for tumor studies. Copyright © 2016. Published by Elsevier B.V.

Effect of calcium citrate on bone integration in a rabbit femur defect model.

Science.gov (United States)

Zhang, Wei; Wang, Wei; Chen, Qing-Yu; Lin, Zhong-Qin; Cheng, Shao-Wen; Kou, Dong-Quan; Ying, Xiao-Zhou; Shen, Yue; Cheng, Xiao-Jie; Nie, Peng-Fei; Li, Xiu-Cui; Rompis, Ferdinand An; Huang, Hang; Zhang, Hua; Mu, Zhong-Lin; Peng, Lei

2012-04-01

To explore effect of calcium citrate on bone integration in a rabbit femur defect model, and to compare the bone formation with different sizes by radiological and histological study. Twenty-four male Japanese white rabbits were randomly divided into three groups (Group A, B, C) in this study. Under anesthesia, defects of four sizes (1.2, 1.5, 2.0 and 2.5 mm) were created in each of the rabbits. Commercially pure calcium citrate powder was placed inside the medullary compartment of the femur (Experimental), while in the contralateral femur (Control) nothing was implanted. The defects were analyzed using radiography and histological analysis by using Imagepro-Plus 6.0 software after animal was sacrificed at 4th(Group A), 6th(Group B) and 8th(Group C) weeks postoperatively. Four samples were analyzed for each size of defect and each healing period. The histological and the radiologic evaluation were performed after sacrification of all rabbits on postoperative 4th and 6th weeks, It showed significant difference between the experimental group and the control group when these defects were less than or equal to 2.0 mm. No statistical difference was observed when these defects were larger than 2.0 mm at all healing periods except at the 4th week. Calcium citrate affects the early periods of bone defects healing mechanism in Japanese white rabbits positively, especially when the defect is not too large. We suggest further studies on calcium citrate to determine the effects of various dosages, administration ways and the experimental time on the bone defects. Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Dose dependency of outcomes of intrapleural fibrinolytic therapy in new rabbit empyema models

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Florova, Galina; Azghani, Ali O.; Buchanan, Ann; Boren, Jake; Allen, Timothy; Rahman, Najib M.; Koenig, Kathleen; Chamiso, Mignote; Karandashova, Sophia; Henry, James; Idell, Steven

2016-01-01

The incidence of empyema (EMP) is increasing worldwide; EMP generally occurs with pleural loculation and impaired drainage is often treated with intrapleural fibrinolytic therapy (IPFT) or surgery. A number of IPFT options are used clinically with empiric dosing and variable outcomes in adults. To evaluate mechanisms governing intrapleural fibrinolysis and disease outcomes, models of Pasteurella multocida and Streptococcus pneumoniae were generated in rabbits and the animals were treated with either human tissue (tPA) plasminogen activator or prourokinase (scuPA). Rabbit EMP was characterized by the development of pleural adhesions detectable by chest ultrasonography and fibrinous coating of the pleura. Similar to human EMP, rabbits with EMP accumulated sizable, 20- to 40-ml fibrinopurulent pleural effusions associated with extensive intrapleural organization, significantly increased pleural thickness, suppression of fibrinolytic and plasminogen-activating activities, and accumulation of high levels of plasminogen activator inhibitor 1, plasminogen, and extracellular DNA. IPFT with tPA (0.145 mg/kg) or scuPA (0.5 mg/kg) was ineffective in rabbit EMP (n = 9 and 3 for P. multocida and S. pneumoniae, respectively); 2 mg/kg tPA or scuPA IPFT (n = 5) effectively cleared S. pneumoniae-induced EMP collections in 24 h with no bleeding observed. Although intrapleural fibrinolytic activity for up to 40 min after IPFT was similar for effective and ineffective doses of fibrinolysin, it was lower for tPA than for scuPA treatments. These results demonstrate similarities between rabbit and human EMP, the importance of pleural fluid PAI-1 activity, and levels of plasminogen in the regulation of intrapleural fibrinolysis and illustrate the dose dependency of IPFT outcomes in EMP. PMID:27343192

Mechanical deformation and glycosaminoglycan content changes in a rabbit annular puncture disc degeneration model.

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Chan, Deva D; Khan, Safdar N; Ye, Xiaojing; Curtiss, Shane B; Gupta, Munish C; Klineberg, Eric O; Neu, Corey P

2011-08-15

Evaluation of degenerated intervertebral discs from a rabbit annular puncture model by using specialized magnetic resonance imaging (MRI) techniques, including displacement encoding with stimulated echoes and a fast-spin echo (DENSE-FSE) acquisition and delayed gadolinium-enhanced MRI of cartilage (dGEMRIC). To evaluate a rabbit disc degeneration model by using various MRI techniques. To determine the displacements and strains, spin-lattice relaxation time (T1), and glycosaminoglycan (GAG) distribution of degenerated discs as compared to normal and adjacent level discs. Annular puncture of the intervertebral disc produces disc degeneration in rabbits. DENSE-FSE has been previously demonstrated in articular cartilage for the measurement of soft tissue displacements and strains. MRI also can measure the T1 of tissue, and dGEMRIC can quantify GAG concentration in cartilage. METHODS.: In eight New Zealand white rabbits, the annulus fibrosis of a lumbar disc was punctured. After 4 weeks, the punctured and cranially adjacent motion segments were isolated for MRI and histology. MRI was used to estimate the disc volume and map T1. DENSE-FSE was used to determine displacements for the estimation of strains. dGEMRIC was then used to determine GAG distributions. Histology and standard MRI indicated degeneration in punctured discs. Disc volume increased significantly at 4 weeks after the puncture. Displacement of the nucleus pulposus was distinct from that of the annulus fibrosis in most untreated discs but not in punctured discs. T1 was significantly higher and GAG concentration significantly lower in punctured discs compared with untreated adjacent level discs. Noninvasive and quantitative MRI techniques can be used to evaluate the mechanical and biochemical changes that occur with animal models of disc degeneration. DENSE-FSE, dGEMRIC, and similar techniques have potential for evaluating the progression of disc degeneration and the efficacy of treatments.

Respiratory and oral vaccination improves protection conferred by the live vaccine strain against pneumonic tularemia in the rabbit model.

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Stinson, Elizabeth; Smith, Le'Kneitah P; Cole, Kelly Stefano; Barry, Eileen M; Reed, Douglas S

2016-10-01

Tularemia is a severe, zoonotic disease caused by a gram-negative bacterium, Francisella tularensis We have previously shown that rabbits are a good model of human pneumonic tularemia when exposed to aerosols containing a virulent, type A strain, SCHU S4. We further demonstrated that the live vaccine strain (LVS), an attenuated type B strain, extended time to death when given by scarification. Oral or aerosol vaccination has been previously shown in humans to offer superior protection to parenteral vaccination against respiratory tularemia challenge. Both oral and aerosol vaccination with LVS were well tolerated in the rabbit with only minimal fever and no weight loss after inoculation. Plasma antibody titers against F. tularensis were higher in rabbits that were vaccinated by either oral or aerosol routes compared to scarification. Thirty days after vaccination, all rabbits were challenged with aerosolized SCHU S4. LVS given by scarification extended time to death compared to mock-vaccinated controls. One orally vaccinated rabbit did survive aerosol challenge, however, only aerosol vaccination extended time to death significantly compared to scarification. These results further demonstrate the utility of the rabbit model of pneumonic tularemia in replicating what has been reported in humans and macaques as well as demonstrating the utility of vaccination by oral and respiratory routes against an aerosol tularemia challenge. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Percutaneous ultrasonic debridement of tendinopathy-a pilot Achilles rabbit model.

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Kamineni, Srinath; Butterfield, Timothy; Sinai, Anthony

2015-05-20

Tendinopathy is a common clinical pathology, with mixed treatment results, especially when chronic. In this study, we examine the effects of an ultrasonic debridement modality in a rabbit tendinopathy model. We asked four questions: (1) Was it possible to create and visualize with ultrasound a tendinopathy lesion in a rabbit Achilles tendon? (2) Was it possible to guide a 19-gauge ultrasonic probe into the tendinopathy lesion? (3) Following ultrasonic treatment, was tendinopathy debris histologically present? and (4) Was the collagen profile qualitatively and quantitatively normalized following treatment? Skeletally mature female New Zealand white rabbits (n = 12) were injected with, ultrasonography localization, 0.150 ml of collagenase into the Achilles tendon. The collagenase-induced Achilles tendinopathy (3 weeks) was treated with percutaneous ultrasonic debridement. The tendons were harvested, at 3 weeks after treatment, and were subjected to histological assessment (modified Movin score) and biochemical analysis (collagen isoform content). Histopathological examination revealed that all tendons injected with collagenase showed areas of hypercellularity and focal areas of tendon disorganization and degeneration. The treated tendons had lower (improved) histopathological scores than injured tendons (P tendon, to qualitative and semi-quantitative levels of a normal tendon. We were successfully able to create a collagenase-injected tendinopathy lesion in a rabbit Achilles tendon and visualize the lesion with an ultrasound probe. A 19-gauge ultrasonic probe was inserted into the tendinopathic lesion under direct ultrasound guidance, and minimal tendinopathic debris remained after treatment. The treated tendon demonstrated a normalized qualitative and semi-quantitative collagen profile and improved histological appearance in the short term. This technique demonstrates scientific merit with respect to the minimally invasive treatment of tendinopathy and warrants

Mathematical models of tumor growth: translating absorbed dose to tumor control probability

International Nuclear Information System (INIS)

Sgouros, G.

1996-01-01

Full text: The dose-rate in internal emitter therapy is low and time-dependent as compared to external beam radiotherapy. Once the total absorbed dose delivered to a target tissue is calculated, however, most dosimetric analyses of radiopharmaceuticals are considered complete. To translate absorbed dose estimates obtained for internal emitter therapy to biologic effect, the growth characteristics, repair capacity, and radiosensitivity of the tumor must be considered. Tumor growth may be represented by the Gompertz equation in which tumor cells increase at an exponential growth rate that is itself decreasing at an exponential rate; as the tumor increases in size, the growth rate diminishes. The empirical Gompertz expression for tumor growth may be derived from a mechanistic model in which growth is represented by a balance between tumor-cell birth and loss. The birth rate is assumed to be fixed, while the cell loss rate is time-dependent and increases with tumor size. The birth rate of the tumors may be related to their potential doubling time. Multiple biopsies of individual tumors have demonstrated a heterogeneity in the potential doubling time of tumors. By extending the mechanistic model described above to allow for sub-populations of tumor cells with different birth rates, the effect of kinetic heterogeneity within a tumor may be examined. Model simulations demonstrate that the cell kinetic parameters of a tumor are predicted to change over time and measurements obtained using a biopsy are unlikely to reflect the kinetics of the tumor throughout its growth history. A decrease in overall tumor mass, in which each sub-population is reduced in proportion to its cell number, i.e., the log-kill assumption, leads to re-growth of a tumor that has a greater proliferation rate. Therapy that is linked to the potential doubling time or to the effective proliferation rate of the tumor may lead to re-growth of a tumor that is kinetically unchanged. The simplest model of

[Correction of lipid peroxidation and antioxidant system disorders by bioflavonoids during modeling of cholesterol atherosclerosis in rabbits].

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Shysh, A M; Pashevin, D O; Dosenko, V Ie; Moĭbenko, O O

2011-01-01

We have studied the influence of bioflavonoids (quercetin, corvitin) on lipid peroxidation and antioxidant enzymes in the modeling of cholesterol atherosclerosis in rabbits. It has been shown that simultaneous administration of the quercetin derivative corvitin suppressed lipid peroxidation. We showed that under hypercholesterolemia, the concentration of malone dialdehyde in myocardial tissue in rabbits is significantly increased, while administration of bioflavonoids decreased the concentration of malone dialdehyde by 38.3%. Furthermore, corvitin caused activating effects on antioxidant enzymes superoxide dismutase and catalase in cardiac tissue. Our data suggest that bioflavonoids are able to suppress lipid peroxidation and prevent the decrease ofantioxidant enzymes activity in rabbits with cholesterol-rich diet induced atherosclerosis.

A rabbit model of atherosclerosis at carotid artery: MRI visualization and histopathological characterization

International Nuclear Information System (INIS)

Ma, Zhan-Long; Teng, Gao-Jun; Chen, Jun; Zhang, Hong-Ying; Cao, Ai-Hong; Ni, Yicheng

2008-01-01

To induce a rabbit model of atherosclerosis at carotid artery, to visualize the lesion evolution with magnetic resonance imaging (MRI), and to characterize the lesion types by histopathology. Atherosclerosis at the right common carotid artery (RCCA) was induced in 23 rabbits by high-lipid diet following balloon catheter injury to the endothelium. The rabbits were examined in vivo with a 1.5-T MRI and randomly divided into three groups of 6 weeks (n=6), 12 weeks (n=8) and 15 weeks (n=9) for postmortem histopathology. The lesions on both MRI and histology were categorized according to the American Heart Association (AHA) classifications of atherosclerosis. Type I and type II of atherosclerotic changes were detected at week 6, i.e., nearly normal signal intensity (SI) of the injured RCCA wall without stenosis on MRI, but with subendothelial inflammatory infiltration and proliferation of smooth muscle cells on histopathology. At week 12, 75.0% and 62.5% of type III changes were encountered on MRI and histopathology respectively with thicker injured RCCA wall of increased SI on T 1 -weighted and proton density (PD)-weighted MRI and microscopically a higher degree of plaque formation. At week 15, carotid atherosclerosis became more advanced, i.e., type IV and type V in 55.6% and 22.2% of the lesions with MRI and 55.6% and 33.3% of the lesions with histopathology, respectively. Statistical analysis revealed a significant agreement (p<0.05) between the MRI and histological findings for lesion classification (r=0.96). A rabbit model of carotid artery atherosclerosis has been successfully induced and noninvasively visualized. The atherosclerotic plaque formation evolved from type I to type V with time, which could be monitored with 1.5-T MRI and confirmed with histomorphology. This experimental setting can be applied in preclinical research on atherosclerosis. (orig.)

Late effects of low-energy gamma-emitting stents in a rabbit iliac artery model

International Nuclear Information System (INIS)

Strauss, Bradley H.; Li, Chris; Whittingham, Heather A.; Tio, Fermin O.; Kutryk, Michael J.B.; Janicki, Christian; Sparkes, John D.; Turnlund, Todd; Sweet, William L.

2002-01-01

Purpose: To determine the long-term dose response of novel low-dose γ-emitting stents in a rabbit iliac artery model. Methods and Materials: Control stents (n=24) and 103 Pd stents 1.0 to 4.0 mCi (n=36) were implanted in the iliac arteries of 30 New Zealand rabbits. Stents were evaluated by intravascular ultrasound (immediately post procedure and before killing) and by histomorphometry. Results: At 26 weeks, 28 rabbits were killed, with no evidence of stent thrombosis. In the body of the stent there was a dose-response relationship with 50% inhibition of intimal hyperplasia at the highest activity compared to control stents (p=0.07) and a significant increase in intimal hyperplasia at the lowest activity (p 103 Pd stents is feasible with reduction of in-stent hyperplasia in a dose-related manner. However, significant narrowing at the stent edges, increased in-stent hyperplasia at lower activities, and incomplete vascular healing with persistence of immature neointima at higher activities are significant limitations

Evaluation of Inhaled Versus Deposited Dose Using the Exponential Dose-Response Model for Inhalational Anthrax in Nonhuman Primate, Rabbit, and Guinea Pig.

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Gutting, Bradford W; Rukhin, Andrey; Mackie, Ryan S; Marchette, David; Thran, Brandolyn

2015-05-01

The application of the exponential model is extended by the inclusion of new nonhuman primate (NHP), rabbit, and guinea pig dose-lethality data for inhalation anthrax. Because deposition is a critical step in the initiation of inhalation anthrax, inhaled doses may not provide the most accurate cross-species comparison. For this reason, species-specific deposition factors were derived to translate inhaled dose to deposited dose. Four NHP, three rabbit, and two guinea pig data sets were utilized. Results from species-specific pooling analysis suggested all four NHP data sets could be pooled into a single NHP data set, which was also true for the rabbit and guinea pig data sets. The three species-specific pooled data sets could not be combined into a single generic mammalian data set. For inhaled dose, NHPs were the most sensitive (relative lowest LD50) species and rabbits the least. Improved inhaled LD50 s proposed for use in risk assessment are 50,600, 102,600, and 70,800 inhaled spores for NHP, rabbit, and guinea pig, respectively. Lung deposition factors were estimated for each species using published deposition data from Bacillus spore exposures, particle deposition studies, and computer modeling. Deposition was estimated at 22%, 9%, and 30% of the inhaled dose for NHP, rabbit, and guinea pig, respectively. When the inhaled dose was adjusted to reflect deposited dose, the rabbit animal model appears the most sensitive with the guinea pig the least sensitive species. © 2014 Society for Risk Analysis.

Characterization of New Zealand White Rabbit Gut-Associated Lymphoid Tissues and Use as Viral Oncology Animal Model.

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Haines, Robyn A; Urbiztondo, Rebeccah A; Haynes, Rashade A H; Simpson, Elaine; Niewiesk, Stefan; Lairmore, Michael D

2016-01-01

Rabbits have served as a valuable animal model for the pathogenesis of various human diseases, including those related to agents that gain entry through the gastrointestinal tract such as human T cell leukemia virus type 1. However, limited information is available regarding the spatial distribution and phenotypic characterization of major rabbit leukocyte populations in mucosa-associated lymphoid tissues. Herein, we describe the spatial distribution and phenotypic characterization of leukocytes from gut-associated lymphoid tissues (GALT) from 12-week-old New Zealand White rabbits. Our data indicate that rabbits have similar distribution of leukocyte subsets as humans, both in the GALT inductive and effector sites and in mesenteric lymph nodes, spleen, and peripheral blood. GALT inductive sites, including appendix, cecal tonsil, Peyer's patches, and ileocecal plaque, had variable B cell/T cell ratios (ranging from 4.0 to 0.8) with a predominance of CD4 T cells within the T cell population in all four tissues. Intraepithelial and lamina propria compartments contained mostly T cells, with CD4 T cells predominating in the lamina propria compartment and CD8 T cells predominating in the intraepithelial compartment. Mesenteric lymph node, peripheral blood, and splenic samples contained approximately equal percentages of B cells and T cells, with a high proportion of CD4 T cells compared with CD8 T cells. Collectively, our data indicate that New Zealand White rabbits are comparable with humans throughout their GALT and support future studies that use the rabbit model to study human gut-associated disease or infectious agents that gain entry by the oral route. © The Author 2016. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Comparison of mouse, guinea pig and rabbit models for evaluation of plague subunit vaccine F1+rV270.

Science.gov (United States)

Qi, Zhizhen; Zhou, Lei; Zhang, Qingwen; Ren, Lingling; Dai, Ruixia; Wu, Benchuan; Wang, Tang; Zhu, Ziwen; Yang, Yonghai; Cui, Baizhong; Wang, Zuyun; Wang, Hu; Qiu, Yefeng; Guo, Zhaobiao; Yang, Ruifu; Wang, Xiaoyi

2010-02-10

In this study, a new subunit vaccine that comprised native F1 and recombinant rV270 was evaluated for protective efficacy using mouse, guinea pig and rabbit models in comparison with the live attenuated vaccine EV76. Complete protection against challenging with 10(6) colony-forming units (CFU) of virulent Yersinia pestis strain 141 was observed for mice immunized with the subunit vaccines and EV76 vaccine. In contrast, the subunit vaccine recipes VII (F1-20 microg+rV270-10 microg) and IX (F1-40 microg+rV270-20 microg) and EV76 vaccine provided 86%, 79% and 93% protection against the same level of challenge in guinea pigs and 100%, 83% and 100% protection in rabbits, respectively. The immunized mice with the vaccines had significantly higher IgG titres than the guinea pigs and rabbits, and the immunized guinea pigs developed significantly higher IgG titres than the rabbits, but the anti-F1 response in guinea pigs was more variable than in the mice and rabbits, indicating that guinea pig is not an ideal model for evaluating protective efficacy of plague subunit vaccine, instead the rabbits could be used as an alternative model. All the immunized animals with EV76 developed a negligible IgG titre to rV270 antigen. Furthermore, analysis of IgG subclasses in the immunized animals showed a strong response for IgG1, whereas those receiving EV76 immunization demonstrated predominant production of IgG1 and IgG2a isotypes. The subunit vaccine and EV76 vaccine are able to provide protection for animals against Y. pestis challenge, but the subunit vaccines have obvious advantages over EV76 in terms of safety of use. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

An animal model for human EBV-associated hemophagocytic syndrome: herpesvirus papio frequently induces fatal lymphoproliferative disorders with hemophagocytic syndrome in rabbits.

Science.gov (United States)

Hayashi, K; Ohara, N; Teramoto, N; Onoda, S; Chen, H L; Oka, T; Kondo, E; Yoshino, T; Takahashi, K; Yates, J; Akagi, T

2001-04-01

Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS) is often associated with fatal infectious mononucleosis. However, the animal model for EBV-AHS has not been developed. We reported the first animal model for EBV-AHS using rabbits infected with EBV-related herpesvirus of baboon (HVP). Eleven of 13 (85%) rabbits inoculated intravenously with HVP-producing cells developed fatal lymphoproliferative disorders (LPD) between 22 and 105 days after inoculation. LPD was also accompanied by hemophagocytic syndrome (HPS) in nine of these 11 rabbits. The peroral spray of cell-free HVP induced the virus infection with increased anti-EBV-viral capsid antigen-IgG titers in three of five rabbits, and two of these three infected rabbits died of LPD with HPS. Autopsy revealed hepatosplenomegaly and swollen lymph nodes. Atypical lymphoid T cells expressing EBV-encoded small RNA-1 infiltrated diffusely in many organs, frequently involving the lymph nodes, spleen, and liver. Hemophagocytic histiocytosis was observed in the lymph nodes, spleen, bone marrow, and thymus. HVP-DNA was detected in the tissues and peripheral blood from the infected rabbits by polymerase chain reaction or Southern blot analysis. Reverse transcriptase-polymerase chain reaction revealed both HVP-EBNA1 and HVP-EBNA2 transcripts, suggesting latency type III infection. These data indicate that the high rate of rabbit LPD with HPS induction is caused by HVP. This system is useful for studying the pathogenesis, prevention, and treatment of human EBV-AHS.

Evaluation of polyethylene glycol/polylactic acid films in the prevention of adhesions in the rabbit adhesion formation and reformation sidewall models.

Science.gov (United States)

Rodgers, K; Cohn, D; Hotovely, A; Pines, E; Diamond, M P; diZerega, G

1998-03-01

To assess the efficacy of bioresorbable films consisting of various polyethylene glycol 6000 and polylactic acid block copolymers on the formation and reformation of adhesions in rabbit models of adhesion development between the sidewall to the adjacent cecum and bowel. The composition of the different polymers was expressed by the number of monomeric units in the block, namely, ethylene oxide (EO) and lactic acid (LA), respectively. Studies of the efficacy of EO/LA films were conducted in rabbit sidewall adhesion formation studies in the presence and absence of blood and in rabbit adhesion reformation studies. REPEL (Life Medical Sciences, Edison, NJ), a film of EO/LA ratio 3.0 manufactured under commercial conditions, was also tested in these animal models. University-based laboratory. New Zealand white rabbits. Placement of films of various EO/LA ratios at the site of injury to the parietal peritoneum. Adhesion formation and reformation. Films of various EO/LA ratios, Seprafilm (Genzyme, Cambridge, MA) and Interceed (Johnson and Johnson Medical, Arlington, TX) placed over an area of excised sidewall at the time of initial injury were highly efficacious in the prevention of adhesion formation. A film of EO/LA ratio 3.7, in contrast with Interceed, was also shown to maintain maximal efficacy in the reduction of adhesion formation in the presence of blood. Further, a film of EO/LA ratio 3.0 produced under commercial conditions, REPEL, was highly efficacious in reducing adhesion development in the rabbit models of adhesion and reformation. These studies suggest that bioresorbable EO/LA films reduced adhesion development in rabbit models of adhesion formation and reformation.

Thermochemical ablation therapy of VX2 tumor using a permeable oil-packed liquid alkali metal.

Directory of Open Access Journals (Sweden)

Ziyi Guo

Full Text Available Alkali metal appears to be a promising tool in thermochemical ablation, but, it requires additional data on safety is required. The objective of this study was to explore the effectiveness of permeable oil-packed liquid alkali metal in the thermochemical ablation of tumors.Permeable oil-packed sodium-potassium (NaK was prepared using ultrasonic mixing of different ratios of metal to oil. The thermal effect of the mixture during ablation of muscle tissue ex vivo was evaluated using the Fluke Ti400 Thermal Imager. The thermochemical effect of the NaK-oil mixture on VX2 tumors was evaluated by performing perfusion CT scans both before and after treatment in 10 VX2 rabbit model tumors. VX2 tumors were harvested from two rabbits immediately after treatment to assess their viability using trypan blue and hematoxylin and eosin (H.E. staining.The injection of the NaK-oil mixture resulted in significantly higher heat in the ablation areas. The permeable oil controlled the rate of heat released during the NaK reaction with water in the living tissue. Perfusion computed tomography and its parameter map confirmed that the NaK-oil mixture had curative effects on VX2 tumors. Both trypan blue and H.E. staining showed partial necrosis of the VX2 tumors.The NaK-oil mixture may be used successfully to ablate tumor tissue in vivo. With reference to the controlled thermal and chemical lethal injury to tumors, using a liquid alkali in ablation is potentially an effective and safe method to treat malignant tumors.

Comparative quantitative monitoring of rabbit haemorrhagic disease viruses in rabbit kittens.

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Matthaei, Markus; Kerr, Peter J; Read, Andrew J; Hick, Paul; Haboury, Stephanie; Wright, John D; Strive, Tanja

2014-06-09

Only one strain (the Czech CAPM-v351) of rabbit haemorrhagic disease virus (RHDV) has been released in Australia and New Zealand to control pest populations of the European rabbit O. cuniculus. Antigenic variants of RHDV known as RHDVa strains are reportedly replacing RHDV strains in other parts of the world, and Australia is currently investigating the usefulness of RHDVa to complement rabbit biocontrol efforts in Australia and New Zealand. RHDV efficiently kills adult rabbits but not rabbit kittens, which are more resistant to RHD the younger they are and which may carry the virus without signs of disease for prolonged periods. These different infection patterns in young rabbits may significantly influence RHDV epidemiology in the field and hence attempts to control rabbit numbers. We quantified RHDV replication and shedding in 4-5 week old rabbits using quantitative real time PCR to assess their potential to shape RHDV epidemiology by shedding and transmitting virus. We further compared RHDV-v351 with an antigenic variant strain of RHDVa in kittens that is currently being considered as a potential RHDV strain for future release to improve rabbit biocontrol in Australia. Kittens were susceptible to infection with virus doses as low as 10 ID50. Virus growth, shedding and transmission after RHDVa infection was found to be comparable or non-significantly lower compared to RHDV. Virus replication and shedding was observed in all kittens infected, but was low in comparison to adult rabbits. Both viruses were shed and transmitted to bystander rabbits. While blood titres indicated that 4-5 week old kittens mostly clear the infection even in the absence of maternal antibodies, virus titres in liver, spleen and mesenteric lymph node were still high on day 5 post infection. Rabbit kittens are susceptible to infection with very low doses of RHDV, and can transmit virus before they seroconvert. They may therefore play an important role in RHDV field epidemiology, in

Accumulation of 125I-factor XI in atheroma of rabbit with hereditary hyperlipidemia (WHHL-rabbit)

International Nuclear Information System (INIS)

Komiyama, Y.; Masuda, M.; Murakami, T.; Nishikado, H.; Egawa, H.; Nishimura, T.; Morii, S.; Murata, K.

1989-01-01

We have studied the turnover and accumulation of rabbit factor XI (F.XI) in atherosclerotic lesion in Watanabe-hereditable hyperlipidemic rabbit (WHHL rabbit) to reveal the participation of blood coagulation in atherosclerotic lesion. Rabbit F.XI was iodinated and administered intravenously to WHHL rabbits and Japanese white rabbits. The turnover of 125 I-rabbit F.XI was significantly faster in WHHL rabbits (T1/2 = 2.84 +/- 0.44 days) than in normal rabbits (T1/2 = 4.44 +/- 0.42 days). The thoracic aorta of WHHL rabbit was strongly labelled with 125 I-rabbit F.XI, in sections obtained after 5 days by en-face autoradiography, whereas no radioactivity was detected in normal aorta. By an immunohistochemical study of WHHL rabbit aorta, we confirmed that many F.XI- and fibrin-related compounds existed in the atheroma, whereas albumin did not in these area. These results suggest that the activation of F.XI proceeds on the atherosclerotic lesions of WHHL rabbits

Allergy to Rabbits. 1

International Nuclear Information System (INIS)

Price, J.A.; Longbottom, J.L.

1986-01-01

Investigations have been carried out into the presence of antibody light chains in rabbit allergenic extracts and the interference in RAST and crossed-radioimmunoelectrophoresis (XRIE) caused by antibodies directed against them. A ''non-specific'' uptake of radioactivity in XRIE has been demonstrated to be caused by direct cross-linking of the 125 I rabbit anti-human IgE by the sheep antibodies in the immunoprecipitate of rabbit light chains. Preincubation with normal rabbit serum blocked this direct uptake of the labelled antibody and enabled specific IgE uptake on the light chains to be demonstrated for rabbit allergic sera. Verification of the allergenicity of the light chains was obtained from a specific light chain RAST. Elution from a Sephacryl S-200 gel filtration column indicated a MW of approx. 50Kd and confirmation of the components as light chain dimers, not Fab fragments, was obtained by allotyping for loci present on heavy chains and light chains in the Fab region. Light chains were detected in urine from rabbits of all ages and in an extract of dust collected in a rabbit housing area. No background staining was observed in XRIE using rabbit antisera, either with rabbit allergic sera with specific IgE or with a human serum containing specific IgG antibodies to rabbit IgG. This latter serum also showed no evidence of uptake on all immunoprecipitates in systems using rabbit antisera, and did not give false positive RAST results when the labelled rabbit anti-human IgE contained unlabelled rabbit IgG. Those sera with specific IgE to light chains showed no uptake in XRIE using rabbit antisera, indicating that the IgE was possibly specific for epitopes revealed by the dissociation on the whole IgG molecule. (author)

The preparation of aneurysm model in rabbits by vessel ligation and elastase-induced technique

International Nuclear Information System (INIS)

Lu Chuan; Xie Qianyu; Liu Linxiang

2010-01-01

Objective: To establish an aneurysm model, which is quite similar to the human intracranial aneurysm in morphology, in rabbits by means of vessel ligation together with elastase-induced technique. Methods: Sixteen New Zealand white rabbits were used in this study. Distal carotid ligation and intraluminal elastase incubation was employed in ten rabbits (study group) to create aneurysm on the right common carotid artery. And surgical suture of a segment of the left carotid common artery was carried out in six rabbits (used as control group) to establish the aneurysm model. DSA exam of the created aneurysms by using catheterization via femoral artery was performed at one week and at one month after surgery. The patency, morphology and pathology of the aneurysms were observed. The results were statistically analyzed. Results: The aneurysms in both groups remained patent after they were created. Angiography one week after the surgery showed that all the aneurysms in study group were patent, while in control group only two aneurysms showed opacification with contrast medium and the remaining four aneurysms were all occluded. DSA at one month after the procedure demonstrated that all the aneurysms in study group remained patent, and the previous two patent aneurysms in control group became occluded. The mean width and length of the aneurysmal cavity in study group immediately after the procedure were (3.70 ± 0.16) mm and (6.53 ± 0.65) mm respectively, which enlarged to (5.06 ± 0.31) mm and (9.0 ± 0.52) mm respectively one month after the surgery. The difference in size changes was statistically significant (P < 0.05). Pathologically, almost complete absence of the internal elastic lamina and medial wall elastin of the aneurysms was observed. Conclusion: The aneurysm model prepared with vessel ligation together with elastase-induced technique carries high patent rate and possesses the feature of spontaneous growing, moreover, its morphology is quite similar to the

Extent of Spine Deformity Predicts Lung Growth and Function in Rabbit Model of Early Onset Scoliosis.

Directory of Open Access Journals (Sweden)

J Casey Olson

Full Text Available Early onset deformity of the spine and chest wall (initiated <8 years of age is associated with increased morbidity at adulthood relative to adolescent onset deformity of comparable severity. Presumably, inhibition of thoracic growth during late stage alveolarization leads to an irreversible loss of pulmonary growth and thoracic function; however the natural history of this disease from onset to adulthood has not been well characterized. In this study we establish a rabbit model of early onset scoliosis to establish the extent that thoracic deformity affects structural and functional respiratory development. Using a surgical right unilateral rib-tethering procedure, rib fusion with early onset scoliosis was induced in 10 young New Zealand white rabbits (3 weeks old. Progression of spine deformity, functional residual capacity, total lung capacity, and lung mass was tracked through longitudinal breath-hold computed tomography imaging up to skeletal maturity (28 weeks old. Additionally at maturity forced vital capacity and regional specific volume were calculated as functional measurements and histo-morphometry performed with the radial alveolar count as a measure of acinar complexity. Data from tethered rib rabbits were compared to age matched healthy control rabbits (N = 8. Results show unilateral rib-tethering created a progressive spinal deformity ranging from 30° to 120° curvature, the severity of which was strongly associated with pulmonary growth and functional outcomes. At maturity rabbits with deformity greater than the median (55° had decreased body weight (89%, right (59% and left (86% lung mass, right (74% and left (69% radial alveolar count, right lung volume at total lung capacity (60%, and forced vital capacity (75%. Early treatment of spinal deformity in children may prevent pulmonary complications in adulthood and these results provide a basis for the prediction of pulmonary development from thoracic structure. This model may

Study of 99Tcm-annexin V distribution in inferior vena cava thrombus models of rabbits

International Nuclear Information System (INIS)

Wu Dayong; Zhang Wenyan; Bian Yanzhu; Hu Yujing

2013-01-01

To study 99 Tc m -Annexin V distribution in inferior vena cava thrombus models of rabbits and uptake of 99 Tc m -Annexin V in fresh and old venous thrombus. Rabbits (n=15) were randomly grouped into 3 groups (the fresh thrombus group, old thrombus group, and control group). The rabbits of two thrombus groups developed inferior vena cava thrombus models by operations. The control group received sham operation. The fresh thrombus group and control group rabbits were injected 99 Tc m -Annexin V after operating 1 d; the old thrombus group 14 d. After 1 h all rabbits were killed by injecting overdose pentobarbital sodium. The thrombus (or the inferior vena cava about 3 cm below inferior pole of right kidney level in the control group rabbits), blood, thrombus area inferior vena cava, head lateral inferior vena cava (except the control group), thigh muscle, stomach, myocardium, pulmonary, liver, kidney, spleen, bone and small intestine were obtained from all group rabbits. The ex tissue and blood were weighed and measured by a Well-type detector. The percentage of the injected dose per gram of ex tissue (or blood) was calculated by the above data. The thrombus to blood, thrombus area inferior vena cava, head lateral inferior vena cava and thigh muscle ratios were calculated by percentage of the injected dose per gram of ex tissue (or blood). The test was used to compare the fresh thrombus group and old thrombus group by SPSS 17.0. The percentage of' the injected dose per gram of thrombi (0.01894± 0.002 16% ID/g) in the fresh thrombus group was higher than the old thrombus group (0.00473±0.001 28% ID/g), P<0.05. The thrombus to blood, thrombus area inferior vena cava, head lateral inferior vena cava and muscle ratios (3.42±1.06, 26.32±13.60, 31.23 ±16.00, 111.62±52.23) in the fresh thrombus group were higher than the old thrombus group (0.98±0.09, 5.12±2.01, 6.25±2.38, 21.82±5.93), P<0.05 for all. All the thrombi of the fresh thrombus group were confirmed

Rabbit analgesia.

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Barter, Linda S

2011-01-01

With the increasing popularity of rabbits as household pets, the complexity of diagnostic and surgical procedures performed on rabbits is increasing, along with the frequency of routine surgical procedures. More practitioners are faced with the need to provide adequate analgesia for this species. Preemptive analgesia prior to planned surgical interventions may reduce nervous system changes in response to noxious input, as well as reduce postoperative pain levels and analgesic drug requirements. Concurrent administration of analgesic drugs to anesthetized rabbits undergoing painful procedures is warranted both pre- and intraoperatively as well as postoperatively. This article discusses the neuropharmacologic and pharmacologic aspects of pain in rabbits, and reviews current protocols for the use of analgesic drugs. Published by Elsevier Inc.

Pure Ethiodized Oil-based Transcatheter Ablative Therapy in Normal Rabbit Kidneys and Kidneys Inoculated with VX-2 Carcinoma

International Nuclear Information System (INIS)

Kónya, András; Stephens, L. Clifton; Wright, Kenneth C.

2011-01-01

Purpose: To evaluate the efficacy of ablation with selective arterial injection of pure ethiodized oil followed by arterial occlusion with 9:1 ethanol–Ethiodol mixture (EEM) and coil placement in normal rabbit kidneys and kidneys inoculated with VX-2 carcinoma. Materials and Methods: All experiments were conducted with Animal Care and Use Committee approval. In six rabbits (group 1), one kidney was embolized with pure Ethiodol until capillary stasis, followed by injection of 9:1 EEM until arterial stasis and then coil placement into the main renal artery. In 12 other rabbits, one kidney was inoculated with VX-2 tumor. Ethiodol and EEM embolization and coil placement followed 7 days later (group 2, n = 6) or 11–14 days later (group 3, n = 6). Kidneys were evaluated (angiography, computed tomography, macro- and microscopy) 7 days after treatment. Results: Capillary stasis was achieved in groups 1, 2, and 3 with (mean ± standard deviation) 0.47 ± 0.03, 0.53 ± 0.02, and 0.56 ± 0.04 ml of pure Ethiodol, followed by 0.47 ± 0.05, 0.42 ± 0.03, and 0.38 ± 0.04 ml of EEM, respectively, which caused complete arterial occlusion in 17 of 18 kidneys. In group 1, all but one kidney showed at least 95% generalized coagulative necrosis. In group 2, all six kidneys exhibited 100% coagulative necrosis, with no viable tumor present. In group 3, 100% coagulative necrosis was present in all kidneys, with a small viable tumor in one. Conclusion: In the rabbit, selective arterial injection of pure Ethiodol can cause complete renal parenchyma and tumor ablation when it is followed by prompt, contiguous, and permanent occlusion of the arterial compartment.

Rabbit models for biomedical research revisited via genome editing approaches

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HONDA, Arata; OGURA, Atsuo

2017-01-01

Although the laboratory rabbit has long contributed to many paradigmatic studies in biology and medicine, it is often considered to be a “classical animal model” because in the last 30 years, the laboratory mouse has been more often used, thanks to the availability of embryonic stem cells that have allowed the generation of gene knockout (KO) animals. However, recent genome-editing strategies have changed this unrivaled condition; so far, more than 10 mammalian species have been added to the list of KO animals. Among them, the rabbit has distinct advantages for application of genome-editing systems, such as easy application of superovulation, consistency with fertile natural mating, well-optimized embryo manipulation techniques, and the short gestation period. The rabbit has now returned to the stage of advanced biomedical research. PMID:28579598

Expression of Neuropeptides and Cytokines in a Rabbit Model of Diabetic Neuroischemic Wound-Healing

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Nabzdyk, Leena Pradhan; Kuchibhotla, Sarada; Guthrie, Patrick; Chun, Maggie; Auster, Michael E; Nabzdyk, Christoph; Deso, Steven; Andersen, Nicholas; LoGerfo, Frank W.; Veves, Aristidis

2013-01-01

Objective The present study is designed to understand the contribution of peripheral vascular disease and peripheral neuropathy to the wound-healing impairment associated with diabetes. Using a rabbit model of diabetic neuroischemic wound-healing we investigated rate of healing, leukocyte infiltration and expression of cytokines, Interleukin (IL)-8 and IL-6, and, neuropeptides, Substance P (SP) and Neuropeptide Y (NPY). Design of study Diabetes was induced in White New Zealand rabbits by administering alloxan while control rabbits received saline. Ten days later animals in both groups underwent surgery. One ear served as a sham and the other was made ischemic (ligation of central+rostral arteries), or neuroischemic (ischemia+ resection of central+rostral nerves). Four, 6mm punch biopsy wounds were created in both ears and wound-healing was followed for ten days using computerized planimetry. Results Non-diabetic sham and ischemic wounds healed significantly more rapidly than diabetic sham and ischemic wounds. Healing was slowest in neuroischemic wounds, irrespective of diabetic status. A high M1/M2 macrophage ratio and a high pro-inflammatory cytokine expression, both indicators of chronic-proinflammatory state, and low neuropeptide expression were seen in pre-injury diabetic skin. Post-injury, in diabetic wounds M1/M2 ratio remained high, the reactive increase in cytokine expression was low and neuropeptide expression was further decreased in neuroischemic wounds. Conclusion This rabbit model illustrates how a combination of a high M1/M2 ratio, a failure to mount post-injury cytokine response as well as a diminished neuropeptide expression contribute to wound-healing impairment in diabetes. The addition of neuropathy to ischemia leads to equivalently severe impaired wound-healing irrespective of diabetes status, suggesting that in the presence of ischemia, loss of neuropeptide function contributes to the impaired healing associated with diabetes. PMID:23755976

Population of computational rabbit-specific ventricular action potential models for investigating sources of variability in cellular repolarisation.

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Philip Gemmell

Full Text Available Variability is observed at all levels of cardiac electrophysiology. Yet, the underlying causes and importance of this variability are generally unknown, and difficult to investigate with current experimental techniques. The aim of the present study was to generate populations of computational ventricular action potential models that reproduce experimentally observed intercellular variability of repolarisation (represented by action potential duration and to identify its potential causes. A systematic exploration of the effects of simultaneously varying the magnitude of six transmembrane current conductances (transient outward, rapid and slow delayed rectifier K(+, inward rectifying K(+, L-type Ca(2+, and Na(+/K(+ pump currents in two rabbit-specific ventricular action potential models (Shannon et al. and Mahajan et al. at multiple cycle lengths (400, 600, 1,000 ms was performed. This was accomplished with distributed computing software specialised for multi-dimensional parameter sweeps and grid execution. An initial population of 15,625 parameter sets was generated for both models at each cycle length. Action potential durations of these populations were compared to experimentally derived ranges for rabbit ventricular myocytes. 1,352 parameter sets for the Shannon model and 779 parameter sets for the Mahajan model yielded action potential duration within the experimental range, demonstrating that a wide array of ionic conductance values can be used to simulate a physiological rabbit ventricular action potential. Furthermore, by using clutter-based dimension reordering, a technique that allows visualisation of multi-dimensional spaces in two dimensions, the interaction of current conductances and their relative importance to the ventricular action potential at different cycle lengths were revealed. Overall, this work represents an important step towards a better understanding of the role that variability in current conductances may play in

Population of computational rabbit-specific ventricular action potential models for investigating sources of variability in cellular repolarisation.

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Gemmell, Philip; Burrage, Kevin; Rodriguez, Blanca; Quinn, T Alexander

2014-01-01

Variability is observed at all levels of cardiac electrophysiology. Yet, the underlying causes and importance of this variability are generally unknown, and difficult to investigate with current experimental techniques. The aim of the present study was to generate populations of computational ventricular action potential models that reproduce experimentally observed intercellular variability of repolarisation (represented by action potential duration) and to identify its potential causes. A systematic exploration of the effects of simultaneously varying the magnitude of six transmembrane current conductances (transient outward, rapid and slow delayed rectifier K(+), inward rectifying K(+), L-type Ca(2+), and Na(+)/K(+) pump currents) in two rabbit-specific ventricular action potential models (Shannon et al. and Mahajan et al.) at multiple cycle lengths (400, 600, 1,000 ms) was performed. This was accomplished with distributed computing software specialised for multi-dimensional parameter sweeps and grid execution. An initial population of 15,625 parameter sets was generated for both models at each cycle length. Action potential durations of these populations were compared to experimentally derived ranges for rabbit ventricular myocytes. 1,352 parameter sets for the Shannon model and 779 parameter sets for the Mahajan model yielded action potential duration within the experimental range, demonstrating that a wide array of ionic conductance values can be used to simulate a physiological rabbit ventricular action potential. Furthermore, by using clutter-based dimension reordering, a technique that allows visualisation of multi-dimensional spaces in two dimensions, the interaction of current conductances and their relative importance to the ventricular action potential at different cycle lengths were revealed. Overall, this work represents an important step towards a better understanding of the role that variability in current conductances may play in experimentally

Titanium and steel fracture fixation plates with different surface topographies: Influence on infection rate in a rabbit fracture model.

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Metsemakers, W J; Schmid, Tanja; Zeiter, Stephan; Ernst, Manuela; Keller, Iris; Cosmelli, Nicolo; Arens, Daniel; Moriarty, T Fintan; Richards, R Geoff

2016-03-01

Implant-related infection is a challenging complication in musculoskeletal trauma surgery. In the present study, we examined the role of implant material and surface topography as influencing factors on the development of infection in an experimental model of plating osteosynthesis in the rabbit. The implants included in this experimental study were composed of: standard Electropolished Stainless Steel (EPSS), standard titanium (Ti-S), roughened stainless steel (RSS) and surface polished titanium (Ti-P). Construct stability and load-to-failure of Ti-P implants was compared to that of Ti-S implants in a rabbit cadaveric model. In an in vivo study, a rabbit humeral fracture model was used. Each rabbit received one of three Staphylococcus aureus inocula, aimed at determining the infection rate at a low, medium and high dose of bacteria. Outcome measures were quantification of bacteria on the implant and in the surrounding tissues, and determination of the infectious dose 50 (ID50). No significant differences were observed between Ti-S and Ti-P regarding stiffness or failure load in the cadaver study. Of the 72 rabbits eventually included in the in vivo study, 50 developed an infection. The ID50 was found to be: EPSS 3.89×10(3) colony forming units (CFU); RSS 8.23×10(3) CFU; Ti-S 5.66×10(3) CFU; Ti-P 3.41×10(3) CFU. Significantly lower bacterial counts were found on the Ti-S implants samples compared with RSS implants (ptitanium and steel implants with conventional or modified topographies. Ti-P implants, which have previously been shown in preclinical studies to reduce complications associated with tissue adherence, do not affect infection rate in this preclinical fracture model. Therefore, Ti-P implants are not expected to affect the infection rate, or influence implant stability in the clinical situation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Magnetic resonance imaging of osteophytic, chondral, and subchondral structures in a surgically-induced osteoarthritis rabbit model.

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Lang Jia

Full Text Available OBJECTIVE: This study aimed to assess changes in osteophytic, chondral, and subchondral structures in a surgically-induced osteoarthritis (OA rabbit model in order to correlate MRI findings with the macroscopic progress of OA and to define the timepoint for disease status in this OA model. METHODS: The OA model was constructed by surgery in thirty rabbits with ten normal rabbits serving as controls (baseline. High-resolution three-dimensional MRI using a 1.5-T coil was performed at baseline, two, four, and eight weeks post-surgery. MRIs of cartilage lesions, subchondral bone lesions, and osteophyte formations were independently assessed by two blinded radiologists. Ten rabbits were sacrificed at baseline, two, four, and eight weeks post-surgery, and macroscopic evaluation was independently performed by two blinded orthopedic surgeons. RESULTS: The signal intensities and morphologies of chondral and subchondral structures by MRI accurately reflected the degree of OA. Cartilage defects progressed from a grade of 0.05-0.15 to 1.15-1.30 to 1.90-1.97 to 3.00-3.35 at each successive time point, respectively (p<0.05. Subchondral bone lesions progressed from a grade of 0.00 to 0.78-0.90 to 1.27-1.58 to 1.95-2.23 at each successive time point, respectively (p = 0.000. Osteophytes progressed from a size (mm of 0.00 to 0.87-1.06 to 1.24-1.87 to 2.21-3.21 at each successive time point, respectively (p = 0.000. CONCLUSIONS: Serial observations revealed that MRI can accurately detect the progression of cartilage lesions and subchondral bone edema over an eight-week period but may not be accurate in detecting osteophyte sizes. Week four post-surgery was considered the timepoint between OA-negative and OA-positive status in this OA model. The combination of this OA model with MRI evaluation should provide a promising tool for the pre-clinical evaluation of new disease-modifying osteoarthritis drugs.

Magnetic resonance imaging of osteophytic, chondral, and subchondral structures in a surgically-induced osteoarthritis rabbit model.

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Jia, Lang; Chen, Jinyun; Wang, Yan; Liu, Yingjiang; Zhang, Yu; Chen, Wenzhi

2014-01-01

This study aimed to assess changes in osteophytic, chondral, and subchondral structures in a surgically-induced osteoarthritis (OA) rabbit model in order to correlate MRI findings with the macroscopic progress of OA and to define the timepoint for disease status in this OA model. The OA model was constructed by surgery in thirty rabbits with ten normal rabbits serving as controls (baseline). High-resolution three-dimensional MRI using a 1.5-T coil was performed at baseline, two, four, and eight weeks post-surgery. MRIs of cartilage lesions, subchondral bone lesions, and osteophyte formations were independently assessed by two blinded radiologists. Ten rabbits were sacrificed at baseline, two, four, and eight weeks post-surgery, and macroscopic evaluation was independently performed by two blinded orthopedic surgeons. The signal intensities and morphologies of chondral and subchondral structures by MRI accurately reflected the degree of OA. Cartilage defects progressed from a grade of 0.05-0.15 to 1.15-1.30 to 1.90-1.97 to 3.00-3.35 at each successive time point, respectively (pSubchondral bone lesions progressed from a grade of 0.00 to 0.78-0.90 to 1.27-1.58 to 1.95-2.23 at each successive time point, respectively (p = 0.000). Osteophytes progressed from a size (mm) of 0.00 to 0.87-1.06 to 1.24-1.87 to 2.21-3.21 at each successive time point, respectively (p = 0.000). Serial observations revealed that MRI can accurately detect the progression of cartilage lesions and subchondral bone edema over an eight-week period but may not be accurate in detecting osteophyte sizes. Week four post-surgery was considered the timepoint between OA-negative and OA-positive status in this OA model. The combination of this OA model with MRI evaluation should provide a promising tool for the pre-clinical evaluation of new disease-modifying osteoarthritis drugs.

Anatomical relationship between the collecting system and the intrarenal arteries in the rabbit: contribution for an experimental model.

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Shalgum, A; Marques-Sampaio, B P S; Dafalla, A; Pereira-Sampaio, M A

2012-04-01

Intrarenal anatomy was studied in detail to evaluate how useful rabbits could be as a urologic model. Only one renal artery was observed, which was divided into dorsal and ventral branches in all cases. Three segmental arteries (cranial, mesorenal and caudal) was the most frequent branching pattern found in both the dorsal and ventral division. There was an important artery related to the ureteropelvic junction in both dorsal and ventral surfaces in all specimens. The cranial pole was supplied by both dorsal and ventral divisions of the renal artery in 23 of 41 casts (56%). Although the cranial pole of the rabbit kidney could be useful as a model because of the resemblances with human kidney, the different relationship between the intrarenal arteries and the kidney collecting system in other regions of the kidney must be taken into consideration by the urologists, when using rabbit kidney in urological research. © 2011 Blackwell Verlag GmbH.

Quantitative analysis of disc degeneration using axial T2 mapping in a percutaneous annular puncture model in rabbits

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Chai, Jee Won; Kim, Su Jin [Dept. of Radiology, SMG-SNU Boramae Medical Center, Seoul (Korea, Republic of); Kang, Heung Sik; Lee, Joon Woo [Dept. of Radiology, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of); Hong, Sung Hwan [Dept. of Radiology, Seoul National University Hospital, Seoul (Korea, Republic of)

2016-02-15

To evaluate T2 relaxation time change using axial T2 mapping in a rabbit degenerated disc model and determine the most correlated variable with histologic score among T2 relaxation time, disc height index, and Pfirrmann grade. Degenerated disc model was made in 4 lumbar discs of 11 rabbits (n = 44) by percutaneous annular puncture with various severities of an injury. Lumbar spine lateral radiograph, MR T2 sagittal scan and MR axial T2 mapping were obtained at baseline and 2 weeks and 4 weeks after the injury in 7 rabbits and at baseline and 2 weeks, 4 weeks, and 6 weeks after the injury in 4 rabbits. Generalized estimating equations were used for a longitudinal analysis of changes in T2 relaxation time in degenerated disc model. T2 relaxation time, disc height index and Pfirrmann grade were correlated with the histologic scoring of disc degeneration using Spearman's rho test. There was a significant difference in T2 relaxation time between uninjured and injured discs after annular puncture. Progressive decrease in T2 relaxation time was observed in injured discs throughout the study period. Lower T2 relaxation time was observed in the more severely injured discs. T2 relaxation time showed the strongest inverse correlation with the histologic score among the variables investigated (r = -0.811, p < 0.001). T2 relaxation time measured with axial T2 mapping in degenerated discs is a potential method to assess disc degeneration.

A new ODE tumor growth modeling based on tumor population dynamics

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Oroji, Amin; Omar, Mohd bin [Institute of Mathematical Sciences, Faculty of Science University of Malaya, 50603 Kuala Lumpur, Malaysia amin.oroji@siswa.um.edu.my, mohd@um.edu.my (Malaysia); Yarahmadian, Shantia [Mathematics Department Mississippi State University, USA Syarahmadian@math.msstate.edu (United States)

2015-10-22

In this paper a new mathematical model for the population of tumor growth treated by radiation is proposed. The cells dynamics population in each state and the dynamics of whole tumor population are studied. Furthermore, a new definition of tumor lifespan is presented. Finally, the effects of two main parameters, treatment parameter (q), and repair mechanism parameter (r) on tumor lifespan are probed, and it is showed that the change in treatment parameter (q) highly affects the tumor lifespan.

A new ODE tumor growth modeling based on tumor population dynamics

International Nuclear Information System (INIS)

Oroji, Amin; Omar, Mohd bin; Yarahmadian, Shantia

2015-01-01

In this paper a new mathematical model for the population of tumor growth treated by radiation is proposed. The cells dynamics population in each state and the dynamics of whole tumor population are studied. Furthermore, a new definition of tumor lifespan is presented. Finally, the effects of two main parameters, treatment parameter (q), and repair mechanism parameter (r) on tumor lifespan are probed, and it is showed that the change in treatment parameter (q) highly affects the tumor lifespan

AV-block and conduction slowing prevail over TdP arrhythmias in the methoxamine-sensitized pro-arrhythmic rabbit model.

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Varkevisser, Rosanne; Vos, Marc A; Beekman, Jet D; Tieland, Ralph G; Van Der Heyden, Marcel A

2015-01-01

The methoxamine-sensitized rabbit model is widely used to screen drugs for proarrhythmic properties, especially repolarization-dependent TdP arrhythmias. With the change of anesthesia and/or sensitizing agent, conduction disturbances have been reported as well. Therefore, we compared currently available in-house anesthetics in order to preserve arrhythmia sensitivity and preclude conduction disturbances. Rabbits were randomly assigned to 3 groups: (1) 35 mg/kg ketamine + 5 mg/kg xylazine; (2) 0.5 mL/kg hypnorm + 3 mg/kg midazolam; (3) 35 mg/kg ketamine + 20 mg/kg propofol. Anesthesia was maintained by 1.5% isoflurane. Concomitant infusion of methoxamine (17 μg/kg/min for 40 minutes) and dofetilide (10 μg/kg/min for 30 minutes) was used to induce arrhythmias. Sole methoxamine infusion exclusively decreased HR in groups 1 and 3. Dofetilide lengthened repolarization, followed in time by PQ/QRS prolongation, second-degree AV block, and subsequently TdP arrhythmias. TdP was seen in 80%, 0%, and 33% of the rabbits in groups 1, 2, and 3, respectively. Decreasing the dose of dofetilide to 5 μg/kg/min in ketamine/xylazine anesthetized rabbits resulted in a drop in TdP incidence (25%) while conduction disturbances persisted. Flunarizine (n = 6) suppressed all TdP arrhythmias while conduction disturbances remained present. TdP incidence in the methoxamine-sensitized rabbit could be dramatically influenced by anesthesia, drug dose, and flunarizine, while conduction slowing remained present. Thus, conduction slowing seems to be the integral outcome in this model. © 2014 Wiley Periodicals, Inc.

Environmental bacteria associated with an institutional rabbit house ...

African Journals Online (AJOL)

There is the need for regular microbiological surveillance to protect our growing rabbitaries and the rabbit models in biomedical research since these latent organisms may produce clinical conditions when the rabbits are exposed to stress conditions. Above all the importance of good hygiene and management in rabbitaries ...

Dose rate effect of 125I irradiation on normal rabbit eyes and experimental choroidal melanoma

International Nuclear Information System (INIS)

Yang, C.M.; Olsen, K.R.; Schwade, J.G.; Houdek, P.V.; Markoe, A.M.; Pisciotta, V.; Xiaodong Wu

1993-01-01

The dose rate effect of radiation by 125 I plaque on choroidal melanoma and normal intraocular tissue was studied. In the first part of the experiment, high activity plaques (HAP) and low activity plagues (LAP) were implanted on rabbit eyes with experimental Greene choroidal melanoma to deliver a total dose of 10 000 cGy to the tumor apex. The mean dose rate calculated at 0.5 mm from the inner sclera in eight eyes with high activity plaques was 3341.5 cGy hr -1 while that in ten eyes with low activity plaques was 239.9 cGy hr -1 . For tumors less than 1.0 mm in height, both groups showed complete tumor regression at the tumor implantation site after plaque treatment. For tumours more than 1.0 mm in height, two out of two eyes in the low activity plaque group and one of four eyes in the high activity plaque group failed to show complete tumor regression. In the second part of the experiment, 125 I plaques were implanted on the sclera of 12 normal rabbits' eyes. Six received high dose rate plaque treatment, while the other six received low dose rate plaque treatment. Clinical and histologic examinations demonstrated more damaging effects to the normal chorioretinal tissues at the plaque implantation site in the high dose rate plaque group. These results suggest that high dose rate plaques are more effective than low dose rate plaques when tumor height is statistically controlled. (Author)

[Surgical model of chronic renal failure: study in rabbits].

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Costa, Andrei Ferreira Nicolau da; Pereira, Lara de Paula Miranda; Ferreira, Manoel Luiz; Silva, Paulo Cesar; Chagar, Vera Lucia Antunes; Schanaider, Alberto

2009-02-01

To establish a model of chronic renal failure in rabbits, with perspectives of its use for therapeutic and repairing actions. Nineteen males, adults rabbits (New Zealand) randomly distributed into three groups were used: Group 1 - Control (n =5); Group 2-Sham (n =7); and Group 3 - Experimental (n =7). They were anaesthetized by using intramuscular Cetamine, Diazepam and Fentanyl followed by Sevorane with vaporizer device. In Group 3, a bipolar left nephrectomy was carried out and after four weeks, it was also done a right nephrectomy. All the samples of the renal tissue were weighed. The Group 2 was only submitted to both abdominal laparotomies, without nephrectomy. Biochemical evaluations, with urea, creatinina, sodium and potassium measurement; abdominal ultrasound scan; scintigraphy and histological analysis were performed in all animals. In group 3 there was a progressive increase of urea (p=0.0001), creatinine (p=0.0001), sodium (p = 0,0002) and potassium (p=0,0003). The comparison of these results with those one of the Groups 1 and 2, in all intervals, revealed blood rising with statistical significant level (p < 0,05). In Group 3, the ultrasound scan identified an increasing of the left kidney size, after 16 weeks and at the 4th week the scintigraphy confirmed the loss of 75% of the left renal mass. In the same group, the histological evaluation showed subcapsular and intersticial fibrosis and also tubular regeneration. The experimental model of IRC is feasible, with animal's survival in middle term which allows the use of this interval like a therapeutic window for testing different approaches in order to repair the kidney damages.

Liquid nitrogen-treated autogenous dentin as bone substitute: an experimental study in a rabbit model.

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Atiya, Basim K; Shanmuhasuntharam, Palasuntharam; Huat, Siar; Abdulrazzak, Shurooq; Oon, Ha

2014-01-01

Different forms of dentin, including untreated, undemineralized, demineralized, boiled, or mixed with other materials, have been evaluated for efficacy as bone substitutes. However, the effects of application of liquid nitrogen-treated dentin for bone grafting remain unknown. The objective of this study was to chronologically evaluate bone healing following grafting with liquid nitrogen-treated dentin in a rabbit model. Autogenous dentin treated with liquid nitrogen at -196°C for 20 minutes was used. In 16 New Zealand White rabbits, a bone defect (5 mm in diameter) was created in each femur and randomly grafted with either autogenous dentin (experimental group) or autogenous bone grafts (positive control). In another four rabbits (negative control), a similar defect in each femur was left empty. The rabbits were sacrificed at 2, 4, 8, and 12 weeks. Explants of grafted sites were harvested for histologic and histomorphometric analysis. At 2 and 4 weeks in both the experimental and positive control groups, accelerated formation of new bone was observed, which was undergoing remodeling at 8 and 12 weeks. The mean new bone score was higher in the experimental than in the negative control groups, but this was not statistically significant. The present results demonstrated that liquid nitrogen-treated autogenous dentin has both osteoconductive and osteoinductive properties and therefore has potential as a bone substitute.

Tumor heterogeneity and progression: conceptual foundations for modeling.

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Greller, L D; Tobin, F L; Poste, G

1996-01-01

A conceptual foundation for modeling tumor progression, growth, and heterogeneity is presented. The purpose of such models is to aid understanding, test ideas, formulate experiments, and to model cancer 'in machina' to address the dynamic features of tumor cell heterogeneity, progression, and growth. The descriptive capabilities of such an approach provides a consistent language for qualitatively reasoning about tumor behavior. This approach provides a schema for building conceptual models that combine three key phenomenological driving elements: growth, progression, and genetic instability. The growth element encompasses processes contributing to changes in tumor bulk and is distinct from progression per se. The progression element subsumes a broad collection of processes underlying phenotypic progression. The genetics elements represents heritable changes which potentially affect tumor character and behavior. Models, conceptual and mathematical, can be built for different tumor situations by drawing upon the interaction of these three distinct driving elements. These models can be used as tools to explore a diversity of hypotheses concerning dynamic changes in cellular populations during tumor progression, including the generation of intratumor heterogeneity. Such models can also serve to guide experimentation and to gain insight into dynamic aspects of complex tumor behavior.

Platelet-Rich Fibrin Improves the Viability of Diced Cartilage Grafts in a Rabbit Model.

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Göral, Ali; Aslan, Cem; Bolat Küçükzeybek, Betül; Işık, Dağhan; Hoşnuter, Mübin; Durgun, Mustafa

2016-04-01

Diced cartilage may be wrapped with synthetic or biological materials before grafting to a recipient site. These materials have unique advantages and disadvantages, and a gold standard is not available. The authors investigated the effects of platelet-rich fibrin (PRF) on the survival of cartilage grafts in a rabbit model. In this experimental study, diced cartilage pieces from the ears of 9 male rabbits were left unwrapped or were wrapped with PRF, oxidized regenerated cellulose, or fascia. Specimens then were placed into subcutaneous pockets prepared on the backs of the rabbits. The animals were sacrificed 2 months after the procedure, and the grafts were excised for macroscopic and histopathologic examination. The cartilage graft wrapped with PRF showed superior viability compared with the cartilage graft wrapped with oxidized regenerated cellulose. No significant differences were found among the other groups. The groups were not significantly different in terms of rates of inflammation, fibrosis, or vascularization. PRF enhances the viability of diced cartilage grafts and should be considered an appropriate biological wrapping material for cartilage grafting. © 2016 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

Assessment of intratumor hypoxia by integrated 18F-FDG PET / perfusion CT in a liver tumor model.

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Yong Wang

Full Text Available Hypoxia in solid tumors occurs when metabolic demands in tumor cells surpass the delivery of oxygenated blood. We hypothesize that the 18F-fluorodeoxyglucose (18F-FDG metabolism and tumor blood flow mismatch would correlate with tumor hypoxia.Liver perfusion computed tomography (CT and 18F-FDG positron emission tomography (PET imaging were performed in twelve rabbit livers implanted with VX2 carcinoma. Under CT guidance, a fiber optic probe was inserted into the tumor to measure the partial pressure of oxygen (pO2. Tumor blood flow (BF and standardized uptake value (SUV were measured to calculate flow-metabolism ratio (FMR. Tumor hypoxia was further identified using pimonidazole immunohistochemical staining. Pearson correlation analysis was performed to determine the correlation between the imaging parameters and pO2 and pimonidazole staining.Weak correlations were found between blood volume (BV and pO2 level (r = 0.425, P = 0.004, SUV and pO2 (r = -0.394, P = 0.007, FMR and pimonidazole staining score (r = -0.388, P = 0.031. However, there was stronger correlation between tumor FMR and pO2 level (r = 0.557, P < 0.001.FMR correlated with tumor oxygenation and pimonidazole staining suggesting it may be a potential hypoxic imaging marker in liver tumor.

An experimental model for measuring gastrointestinal bleeding rate using Tc-99m DTPA in rabbits

International Nuclear Information System (INIS)

Owunwanne, A.; Abdel-Dayem, H.M.; Sadek, S.; Yakoub, T.; Mahajan, K.K.; Ericsson, S.B.

1987-01-01

An animal experimental model to measure the rate of gastrointestinal bleeding rate in a rabbit using Tc-99m DTPA is described. It was possible to detect a bleeding rate of 0.1 ml/min. However, the model could not be used to calculate the minimum amount of radioactivity needed to detect the bleeding site. (orig.) [de

Tumor localization of 131I-labeled antibodies by radionuclide imaging

International Nuclear Information System (INIS)

Ghose, T.; Tai, J.; Aquino, J.; Guclu, A.; Norvell, S.; MacDondald, A.

1975-01-01

Intravenous injections of 131 I-labeled anti-EL4 lymphoma antibodies showed progressive localization of radioactivity in EL4 transplants but not in B16 melanoma in mice carrying both tumors. Normal rabbit globulin labeled with 131 I did not localize in either tumor and cleared more slowly from the internal organs. Metastatic localization of intravenous 131 I-labeled anti-tumor antibodies was also observed in two cancer patients. (U.S.)

The Ultrasonographic Findings of Trigger Points of Myofascial Pain Syndrome in a Rabbit Model

International Nuclear Information System (INIS)

Moon, Kyung Mi; Park, Seog Hee; Lee, Sang Heon; Kim, Joo Hyun; Kim, Han Kyum

2005-01-01

Myofascial pain syndrome (MPS) is a common cause of musculoskeletal pain. Myofascial trigger points (MTrPs) have been repeatedly described by numerous authors. However, there have been few studies in which their existence and behavior was supported and their location confirmed. The purpose of this study was to determine whether diagnostic ultrasonography is an objective diagnostic tool which is able to significantly identify or detect the soft tissue changes in the region of clinically identified active MTrPs by using a rabbit experimental model. Ten MPS model rabbits were used in this study. We made an MPS animal model by causing the rabbits to overuse one leg for 3 weeks by cutting the contralateral L4 spinal nerve root. We compared the ultrasonographic findings of the taut band at pre-OP with those at post-OP during the consecutive three week period. To find the taut bands of the muscle, after skin exposure, the muscles were gently rubbed or pinched with the thumb and index finger on the two opposing surfaces of the muscle across the direction of the fibers. Then, the muscle was held in the same way, but with a 5-8 MHz stick probe being used in place of the thumb. After the palpation of various muscles, we selected the hardest and largest myofascial trigger nodule, in order to observe the ultrasonographic and power Doppler findings of the MPS. The size, shape, echogenecity and vascularity of the MTrPs were observed. The analysis of the results of the ultrasonography revealed that all MTrPs have a hyperechoic area. The mean thickness of the hyperechoic lesion in the biceps was 0.96±0.14 cm in the MPS site (at pre-OP?), and 0.49±0.12 cm at post-OP 3weeks (p < 0.01). The hyperechoic lesions in all of the studied biceps femoris of the rabbits were observed by high resolution ultrasonography. No definitively decreased vascularity was observed within the hyperechoic area by power Doppler imaging. Until now, there has been no objective method for the diagnosis of MPS

Cyclophosphamide Enhances Human Tumor Growth in Nude Rat Xenografted Tumor Models

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Yingjen Jeffrey Wu

2009-02-01

Full Text Available The effect of the immunomodulatory chemotherapeutic agent cyclophosphamide (CTX on tumor growth was investigated in primary and metastatic intracerebral and subcutaneous rat xenograft models. Nude rats were treated with CTX (100 mg/kg, intraperitoneally 24 hours before human ovarian carcinoma (SKOV3, small cell lung carcinoma (LX-1 SCLC, and glioma (UW28, U87MG, and U251 tumor cells were inoculated subcutaneously, intraperitoneally, or in the right cerebral hemisphere or were infused into the right internal carotid artery. Tumor development was monitored and recorded. Potential mechanisms were further investigated. Only animals that received both CTX and Matrigel showed consistent growth of subcutaneous tumors. Cyclophosphamide pretreatment increased the percentage (83.3% vs 0% of animals showing intraperitoneal tumors. In intracerebral implantation tumor models, CTX pretreatment increased the tumor volume and the percentage of animals showing tumors. Cyclophosphamide increased lung carcinoma bone and facial metastases after intra-arterial injection, and 20% of animals showed brain metastases. Cyclophosphamide transiently decreased nude rat white blood cell counts and glutathione concentration, whereas serum vascular endothelial growth factor was significantly elevated. Cyclophosphamide also increased CD31 reactivity, a marker of vascular endothelium, and macrophage (CD68-positive infiltration into glioma cell-inoculated rat brains. Cyclophosphamide may enhance primary and metastatic tumor growth through multiple mechanisms, including immune modulation, decreased response to oxidative stress, increased tumor vascularization, and increased macrophage infiltration. These findings may be clinically relevant because chemotherapy may predispose human cancer subjects to tumor growth in the brain or other tissues.

PHARMACOKINETIC VARIATIONS OF OFLOXACIN IN NORMAL AND FEBRILE RABBITS

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M. AHMAD, H. RAZA, G. MURTAZA AND N. AKHTAR

2008-12-01

Full Text Available The influence of experimentally Escherichia coli-induced fever (EEIF on the pharmacokinetics of ofloxacin was evaluated. Ofloxacin was administered @ 20 mg.kg-1 body weight intravenously to a group of eight healthy rabbits and compared these results to values in same eight rabbits with EEIF. Pharmacokinetic parameters of ofloxacin in normal and febrile rabbits were determined by using two compartment open kinetic model. Peak plasma level (Cmax and area under the plasma concentration-time curve (AUC0-α in normal and febrile rabbits did not differ (P>0.05. However, area under first moment of plasma concentration-time curve (AUMC0-α in febrile rabbits was significantly (P<0.05 higher than that in normal rabbits. Mean values for elimination rate constant (Ke, elimination half life (t1/2β and apparent volume of distribution (Vd were significantly (P<0.05 lower in febrile rabbits compared to normal rabbits, while mean residence time (MRT and total body clearance (Cl of ofloxacin did not show any significant difference in the normal and febrile rabbits. Clinical significance of the above results can be related to the changes in the volume of distribution and elimination half life that illustrates an altered steady state in febrile condition; hence, the need for an adjustment of dosage regimen in EEIF is required.

Correlation of Hypoxia-Inducible Factor 1α with Angiogenesis in Liver Tumors After Transcatheter Arterial Embolization in an Animal Model

International Nuclear Information System (INIS)

Liang Bin; Zheng Chuansheng; Feng, Gan-Sheng; Wu Hanping; Wang Yong; Zhao Hui; Qian Jun; Liang Huimin

2010-01-01

This study sought to determine the expression of hypoxia-inducible factor 1α (HIF-1α) and its relation to angiogenesis in liver tumors after transcatheter arterial embolization (TAE) in an animal model. A total of 20 New Zealand White rabbits were implanted with VX2 tumor in liver. TAE-treated group animals (n = 10) received TAE with polyvinyl alcohol particles. Control group animals (n = 10) received sham embolization with distilled water. Six hours or 3 days after TAE, animals were humanely killed, and tumor samples were collected. Immunohistochemical staining was performed to evaluate HIF-1α and vascular endothelial growth factor (VEGF) protein expression and microvessel density (MVD). Real-time polymerase chain reaction was performed to examine VEGF mRNA levels. The levels of HIF-1α protein were significantly higher in TAE-treated tumors than those in the control tumors (P = 0.001). HIF-1α protein was expressed in viable tumor cells that were located predominantly at the periphery of necrotic tumor regions. The levels of VEGF protein and mRNA, and mean MVD were significantly increased in TAE-treated tumors compared with the control tumors (P = 0.001, 0.000, and 0.001, respectively). HIF-1α protein level was significantly correlated with VEGF mRNA (r = 0.612, P = 0.004) and protein (r = 0.554, P = 0.011), and MVD (r = 0.683, P = 0.001). We conclude that HIF-1α is overexpressed in VX2 tumors treated with TAE as a result of intratumoral hypoxia generated by the procedure and involved in activation of the TAE-associated tumor angiogenesis. HIF-1α might represent a promising therapeutic target for antiangiogenesis in combination with TAE against liver tumors.

Insulin versus Lipid Emulsion in a Rabbit Model of Severe Propranolol Toxicity: A Pilot Study

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Martyn Harvey

2011-01-01

Full Text Available Background and objective. Beta-blocker overdose may result in intractable cardiovascular collapse despite conventional antidotal treatments. High dose insulin/glucose (ING, and more recently intravenous lipid emulsion (ILE, have been proposed as potentially beneficial therapies in beta blocker intoxication. We compare efficacy of the novel antidotes ING, with ILE, in a rabbit model of combined enteric/intravenous propranolol toxicity. Methods. Sedated, mechanically ventilated and invasively monitored New Zealand White rabbits underwent mini-laparotomy and enterostomy formation with 40 mg/kg propranolol instilled into the proximal small bowel. At 30 minutes propranolol infusion was commenced at 4 mg/kg/hr and continued to a target mean arterial pressure (MAP of 50% baseline MAP. Animals were resuscitated with insulin at 3 U/kg plus 0.5 g/kg glucose (ING group, or 10 mL/kg 20% Intralipid (ILE group. Results. Rate pressure product (RPP; RPP = heart rate × mean arterial pressure was greatest in the ING group at 60 minutes (P<.05. A trend toward greater heart rate was observed in the ING group (P=.06. No difference was observed in survival between groups (4/5 ING versus 2/5 ILE; P=.524. Conclusions. High dose insulin resulted in greater rate pressure product compared with lipid emulsion in this rabbit model of severe enteric/intravenous propranolol toxicity.

Predicting occupancy for pygmy rabbits in Wyoming: an independent evaluation of two species distribution models

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Germaine, Stephen S.; Ignizio, Drew; Keinath, Doug; Copeland, Holly

2014-01-01

Species distribution models are an important component of natural-resource conservation planning efforts. Independent, external evaluation of their accuracy is important before they are used in management contexts. We evaluated the classification accuracy of two species distribution models designed to predict the distribution of pygmy rabbit Brachylagus idahoensis habitat in southwestern Wyoming, USA. The Nature Conservancy model was deductive and based on published information and expert opinion, whereas the Wyoming Natural Diversity Database model was statistically derived using historical observation data. We randomly selected 187 evaluation survey points throughout southwestern Wyoming in areas predicted to be habitat and areas predicted to be nonhabitat for each model. The Nature Conservancy model correctly classified 39 of 77 (50.6%) unoccupied evaluation plots and 65 of 88 (73.9%) occupied plots for an overall classification success of 63.3%. The Wyoming Natural Diversity Database model correctly classified 53 of 95 (55.8%) unoccupied plots and 59 of 88 (67.0%) occupied plots for an overall classification success of 61.2%. Based on 95% asymptotic confidence intervals, classification success of the two models did not differ. The models jointly classified 10.8% of the area as habitat and 47.4% of the area as nonhabitat, but were discordant in classifying the remaining 41.9% of the area. To evaluate how anthropogenic development affected model predictive success, we surveyed 120 additional plots among three density levels of gas-field road networks. Classification success declined sharply for both models as road-density level increased beyond 5 km of roads per km-squared area. Both models were more effective at predicting habitat than nonhabitat in relatively undeveloped areas, and neither was effective at accounting for the effects of gas-energy-development road networks. Resource managers who wish to know the amount of pygmy rabbit habitat present in an

The cooperative effect of p53 and Rb in local nanotherapy in a rabbit VX2 model of hepatocellular carcinoma

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Dong S

2013-10-01

Full Text Available Shengli Dong,1 Qibin Tang,2 Miaoyun Long,3 Jian Guan,4 Lu Ye,5 Gaopeng Li6 1Department of General Surgery, The Second Hospital of Shanxi Medical University, Shanxi Medical University, Taiyuan, Shanxi Province, 2Department of Hepatobiliopancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 3Department of Thyroid and Vascular Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 4Department of Radiology, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 5Infection Department, Guangzhou No 8 Hospital, Guangzhou, Guangdong Province, 6Department of Ultrasound, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, People's Republic of China Background/aim: A local nanotherapy (LNT combining the therapeutic efficacy of trans-arterial embolization, nanoparticles, and p53 gene therapy has been previously presented. The study presented here aimed to further improve the incomplete tumor eradication and limited survival enhancement and to elucidate the molecular mechanism of the LNT. Methods: In a tumor-targeting manner, recombinant expressing plasmids harboring wild-type p53 and Rb were either co-transferred or transferred separately to rabbit hepatic VX2 tumors in a poly-L-lysine-modified hydroxyapatite nanoparticle nanoplex and Lipiodol® (Guerbet, Villepinte, France emulsion via the hepatic artery. Subsequent co-expression of p53 and Rb proteins within the treated tumors was investigated by Western blotting and in situ analysis by laser-scanning confocal microscopy. The therapeutic effect was evaluated by the tumor growth velocity, apoptosis and necrosis rates, their sensitivity to Adriamycin® (ADM, mitomycin C, and fluorouracil, the microvessel density of tumor tissue, and the survival time of animals. Eventually, real-time polymerase chain reaction and enhanced chemiluminescence Western blotting

Oxidative Damage and Mitochondrial Injuries Are Induced by Various Irrigation Pressures in Rabbit Models of Mild and Severe Hydronephrosis

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Cao, Zhixiu; Yu, Weimin; Li, Wei; Cheng, Fan; Rao, Ting; Yao, Xiaobing; Zhang, Xiaobin; Larré, Stéphane

2015-01-01

Objective We aimed to study whether tolerance to irrigation pressure could be modified by evaluating the oxidative damage of obstructed kidneys based on rabbit models experiencing different degrees of hydronephrosis. Methods A total of 66 rabbits were randomly divided into two experimental groups and a control group. In the experimental groups, the rabbits underwent a surgical procedure inducing mild (group M, n=24) or severe (group S, n=24) hydronephrosis. In each experimental group, the rabbits were then randomly divided into 4 subgroups (M0-M3 and S0-S3) consisting of 6 rabbits each. Group 0 received no perfusion. Groups 1 through 3 were perfused with 20, 60 and 100 mmHg fluid, respectively. For the control group, after a sham operation was performed, the rabbits were divided into 4 subgroups and were perfused with fluid at 0, 20, 60 or 100 mmHg of pressure. Kidney injuries was evaluated by neutrophil gelatinase associated lipocalin (NGAL). Oxidative damage was assessed by analyzing superoxide dismutase (Mn-SOD) activity, malondialdehyde (MDA) levels, glutathione reductase (GR), catalase (CAT) and peroxide (H2O2) levels, mitochondrial injuries was assessed by mitochondrial membrane potential (MMP), the mitochondrial ultrastructure and tubular cell apoptosis. Results In the experimental groups, all results were similar for groups 0 and 1. In group 2, abnormalities were observed in the S group only, and the kidneys of rabbits in group 3 suffered oxidative damage and mitochondrial injuries with increased NGAL, decreased Mn-SOD, GR and CAT,increased MDA and H2O2, lower levels of MMP, mitochondrial vacuolization and an increased apoptotic index. Conclusion In rabbits, severely obstructed kidneys were more susceptible to oxidative damage and mitochondrial injury than mildly obstructed kidneys when subjected to higher degrees of kidney perfusion pressure. PMID:26090815

Oxidative Damage and Mitochondrial Injuries Are Induced by Various Irrigation Pressures in Rabbit Models of Mild and Severe Hydronephrosis.

Directory of Open Access Journals (Sweden)

Zhixiu Cao

Full Text Available We aimed to study whether tolerance to irrigation pressure could be modified by evaluating the oxidative damage of obstructed kidneys based on rabbit models experiencing different degrees of hydronephrosis.A total of 66 rabbits were randomly divided into two experimental groups and a control group. In the experimental groups, the rabbits underwent a surgical procedure inducing mild (group M, n=24 or severe (group S, n=24 hydronephrosis. In each experimental group, the rabbits were then randomly divided into 4 subgroups (M0-M3 and S0-S3 consisting of 6 rabbits each. Group 0 received no perfusion. Groups 1 through 3 were perfused with 20, 60 and 100 mmHg fluid, respectively. For the control group, after a sham operation was performed, the rabbits were divided into 4 subgroups and were perfused with fluid at 0, 20, 60 or 100 mmHg of pressure. Kidney injuries was evaluated by neutrophil gelatinase associated lipocalin (NGAL. Oxidative damage was assessed by analyzing superoxide dismutase (Mn-SOD activity, malondialdehyde (MDA levels, glutathione reductase (GR, catalase (CAT and peroxide (H2O2 levels, mitochondrial injuries was assessed by mitochondrial membrane potential (MMP, the mitochondrial ultrastructure and tubular cell apoptosis.In the experimental groups, all results were similar for groups 0 and 1. In group 2, abnormalities were observed in the S group only, and the kidneys of rabbits in group 3 suffered oxidative damage and mitochondrial injuries with increased NGAL, decreased Mn-SOD, GR and CAT,increased MDA and H2O2, lower levels of MMP, mitochondrial vacuolization and an increased apoptotic index.In rabbits, severely obstructed kidneys were more susceptible to oxidative damage and mitochondrial injury than mildly obstructed kidneys when subjected to higher degrees of kidney perfusion pressure.

Intrinsic connectivity of neural networks in the awake rabbit.

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Schroeder, Matthew P; Weiss, Craig; Procissi, Daniel; Disterhoft, John F; Wang, Lei

2016-04-01

The way in which the brain is functionally connected into different networks has emerged as an important research topic in order to understand normal neural processing and signaling. Since some experimental manipulations are difficult or unethical to perform in humans, animal models are better suited to investigate this topic. Rabbits are a species that can undergo MRI scanning in an awake and conscious state with minimal preparation and habituation. In this study, we characterized the intrinsic functional networks of the resting New Zealand White rabbit brain using BOLD fMRI data. Group independent component analysis revealed seven networks similar to those previously found in humans, non-human primates and/or rodents including the hippocampus, default mode, cerebellum, thalamus, and visual, somatosensory, and parietal cortices. For the first time, the intrinsic functional networks of the resting rabbit brain have been elucidated demonstrating the rabbit's applicability as a translational animal model. Without the confounding effects of anesthetics or sedatives, future experiments may employ rabbits to understand changes in neural connectivity and brain functioning as a result of experimental manipulation (e.g., temporary or permanent network disruption, learning-related changes, and drug administration). Copyright © 2016 Elsevier Inc. All rights reserved.

Assessment of tumoricidal efficacy and response to treatment with 18F-FDG PET/CT after intraarterial infusion with the antiglycolytic agent 3-bromopyruvate in the VX2 model of liver tumor.

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Liapi, Eleni; Geschwind, Jean-Francois H; Vali, Mustafa; Khwaja, Afsheen A; Prieto-Ventura, Veronica; Buijs, Manon; Vossen, Josephina A; Ganapathy-Kanniappan, Shanmugasudaram; Ganapathy, Shanmugasudaram; Wahl, Richard L

2011-02-01

The purpose of this study was to determine the effects of 3-bromopyruvate (3-BrPA) on tumor glucose metabolism as imaged with (18)F-FDG PET/CT at multiple time points after treatment and compare them with those after intraarterial control injections of saline. Twenty-three New Zealand White rabbits implanted intrahepatically with VX2 tumors were assigned to 1 of 2 groups: 14 rabbits were assigned to the treatment group (TG) and 9 to the saline control group (SG). All animals were infused with 25 mL of either 1.75 mM 3-BrPA or saline over 1 h via a 2-French catheter, which was secured in the hepatic artery. For PET/CT, the animals were injected with 37 MBq of (18)F-FDG at 1 d before treatment and 2 h, 24 h, and 1 wk after treatment. Tumor size, tumor and liver maximal standardized uptake value (SUV(max)), and tumor-to-background ratios were calculated for all studies. Seven TG and 5 SG animals were sacrificed at 1 wk after treatment for histopathologic analysis. Intense (18)F-FDG uptake was seen in untreated tumors. A significant reduction in tumor SUV(max) was noted in TG animals, when compared with SG animals, at 1 wk after treatment (P = 0.006). The tumor-to-liver background ratio in the TG animals, compared with the SG animals, was significantly reduced as early as 24 h after treatment (P = 0.01) and remained reduced at 1 wk (P = 0.003). Tumor SUV(max) increased from the baseline levels at 7 d in controls (P = 0.05). The histopathologic analysis of explanted livers revealed increased tumor necrosis in all TG samples. There was a significant inverse correlation (r(2) = 0.538, P = 0.005) between the percentage of tumor necrosis on histopathology and tumor SUV(max) on (18)F-FDG PET at 7 d after treatment with 3-BrPA. Intraarterial injection of 3-BrPA resulted in markedly decreased (18)F-FDG uptake as imaged by PET/CT and increased tumor necrosis on histopathology at 1 wk after treatment in the VX2 rabbit liver tumor. PET/CT appears to be a useful means to follow

Rabbit urethra replacement with a defined biomatrix or small intestinal submucosa.

NARCIS (Netherlands)

Nuininga, J.E.; Moerkerk, H.; Hanssen, A.; Hulsbergen-van de Kaa, C.A.; Oosterwijk-Wakka, J.C.; Oosterwijk, E.; Gier, R.P.E. de; Schalken, J.A.; Kuppevelt, A.H.M.S.M. van; Feitz, W.F.J.

2003-01-01

OBJECTIVE: The evaluation of collagen-based biomatrix (SIS COOK((R))) in comparison to a biochemically reconstructed biomatrix for replacement of the urethra in a rabbit model as a preclinical model. MATERIAL AND METHODS: Rabbits underwent partial urethra replacement (resection of 0.5 to 1.0 cm

Influence of olive oil on alveolar bone response during orthodontic retention period: rabbit model study.

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Al-Hamdany, Afrah K; Al-Khatib, Ali R; Al-Sadi, Hafidh I

2017-08-01

This study attempted to evaluate clinically and histologically the effects of olive oil (Ol) consumption on orthodontic relapse after the retention period. Thirty apparently healthy female albino rabbits, weight more than 1000 g each was used in this study. The animals were grouped randomly into six groups of five animals each: two control and four experimental groups. In control groups, the relapse was estimated either at zero day, or at the end of the fourth week after orthodontic retention period. In the experimental groups, the animals' groups received Ol, 7.7, or 15.4 ml/kg b.w. per day during the orthodontic retention period. The relapse was estimated either at zero day, or at the end of the fourth week after orthodontic retention period for each concentration. Modified fixed orthodontic appliances were attached to the rabbits' lower central incisors. Each rabbit received orthodontic intervention for one week, followed by six weeks retention period. At the end of the experiments, the clinical and histological investigations were conducted. Data analyses were performed at the level of p orthodontic retention period, especially at 15.4 ml/kg b.w. per day concentration, clinically reduced orthodontic relapse on rabbit model. Histologically, Ol increased osteoblasts and osteocytes counts and the relative amount of bone mineralization of connective tissue layer forming alveolar bone (AB) at the end of four weeks after the orthodontic retention period.

Derivation of Rabbit Embryonic Stem Cells from Vitrified–Thawed Embryos

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Chen, Chien-Hong; Li, Yi; Hu, Yeshu; An, Li-You; Yang, Lan; Zhang, Jifeng; Chen, Y. Eugene

2015-01-01

Abstract The rabbit is a useful animal model for regenerative medicine. We previously developed pluripotent rabbit embryonic stem cell (rbESC) lines using fresh embryos. We also successfully cryopreserved rabbit embryos by vitrification. In the present work, we combined these two technologies to derive rbESCs using vitrified–thawed (V/T) embryos. We demonstrate that V/T blastocysts (BLs) can be used to derive pluripotent rbESCs with efficiencies comparable to those using fresh BLs. These ESCs are undistinguishable from the ones derived from fresh embryos. We tested the developmental capacity of rbESCs derived from V/T embryos by BL injection experiments and produced chimeric kits. Our work adds cryopreservation to the toolbox of rabbit stem cell research and applications and will greatly expand the available research materials for regenerative medicine in a clinically relevant animal model. PMID:26579970

FDTD analysis of temperature elevation in the lens of human and rabbit models due to near-field and far-field exposures at 2.45 GHz

International Nuclear Information System (INIS)

Oizumi, T.; Laakso, I.; Hirata, A.; Fujiwara, O.; Watanabe, S.; Taki, M.; Kojima, M.; Sasaki, H.; Sasaki, K.

2013-01-01

The eye is said to be one of the most sensitive organs to microwave heating. According to previous studies, the possibility of microwave-induced cataract formation has been experimentally investigated in rabbit and monkey eyes, but not for the human eye due to ethical reasons. In the present study, the temperature elevation in the lens, the skin around the eye and the core temperature of numerical human and rabbit models for far-field and near-field exposures at 2.45 GHz are investigated. The temperature elevations in the human and rabbit models were compared with the threshold temperatures for inducing cataracts, thermal pain in the skin and reversible health effects such as heat exhaustion or heat stroke. For plane-wave exposure, the core temperature elevation is shown to be essential both in the human and in the rabbit models as suggested in the international guidelines and standards. For localised exposure of the human eye, the temperature elevation of the skin was essential, and the lens temperature did not reach its threshold for thermal pain. On the other hand, the lens temperature elevation was found to be dominant for the rabbit eye. (authors)

FDTD analysis of temperature elevation in the lens of human and rabbit models due to near-field and far-field exposures at 2.45 GHz.

Science.gov (United States)

Oizumi, Takuya; Laakso, Ilkka; Hirata, Akimasa; Fujiwara, Osamu; Watanabe, Soichi; Taki, Masao; Kojima, Masami; Sasaki, Hiroshi; Sasaki, Kazuyuki

2013-07-01

The eye is said to be one of the most sensitive organs to microwave heating. According to previous studies, the possibility of microwave-induced cataract formation has been experimentally investigated in rabbit and monkey eyes, but not for the human eye due to ethical reasons. In the present study, the temperature elevation in the lens, the skin around the eye and the core temperature of numerical human and rabbit models for far-field and near-field exposures at 2.45 GHz are investigated. The temperature elevations in the human and rabbit models were compared with the threshold temperatures for inducing cataracts, thermal pain in the skin and reversible health effects such as heat exhaustion or heat stroke. For plane-wave exposure, the core temperature elevation is shown to be essential both in the human and in the rabbit models as suggested in the international guidelines and standards. For localised exposure of the human eye, the temperature elevation of the skin was essential, and the lens temperature did not reach its threshold for thermal pain. On the other hand, the lens temperature elevation was found to be dominant for the rabbit eye.

Comparison of microporous polysaccharide hemospheres and Ankaferd Blood Stopper in a rabbit epistaxis model.

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Yurttas, Veysel; Sereflican, Murat; Terzi, Elçin Hakan; Ozyalvaçlı, Gulzade; Kazaz, Hasan

2016-04-01

The aim of this study was to evaluate the histopathological impact, effectiveness, and safety of two hemostatic agents, Ankaferd Blood Stopper (ABS) and microporous polysaccharide hemospheres (MPH), in an experimental rabbit epistaxis model. Rabbits were randomly assigned, using a computerized random number generator, to the following three groups of six animals: group 1 (control, irrigated with saline); group 2 (ABS-treated); and group 3 (MPH-treated). In all groups, a standardized rabbit epistaxis model was used. Hemostasis time and extent of nasal bleeding were measured to compare the hemostatic effect of ABS and MPH among groups. Septums were removed for histopathological analysis, 7 days after the procedure. ABS reduced hemostasis time to 104.2 s and amount of bleeding to 20.5 mg. MPH reduced hemostasis time to 71.7 s and amount of bleeding to 11.5 mg. Mean bleeding time in wounds administered ABS and MPH was significantly shorter compared with wounds administered isotonic saline solution (p = 0.004). ABS and MPH application decreased bleeding significantly compared with the control group (p = 0.004). Bleeding time and amount in the MPH group was significantly reduced compared with the ABS group (p = 0.013 and p = 0.004, respectively). There was no significant difference in the histopathological evaluation results between the ABS, MPH, and control groups. Our data indicate that both ABS and MPH represent safe, effective, and fast-acting hemostatic agents in the management of epistaxis. MPH was more effective than ABS in terms of hemostasis time and amount of bleeding.

STUDIES BASED ON A MALIGNANT TUMOR OF THE RABBIT

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Brown, Wade H.; Pearce, Louise

1923-01-01

Data bearing on the occurrence and distribution of metastases, as recorded in the preceding papers of the series, are analyzed with reference to the parts played by the tumor cell and by conditions which influence cell distribution and cell growth. It is shown that, while the tumor cell is an essential element in the production of metastases, its influence is relatively constant, and that the prime factors responsible for variations in the occurrence and distribution of metastatic growths are conditions that influence cell distribution or that affect the viability of the cell during transport, and conditions that affect the nutrition of the cell wherever it may become lodged. It is further shown that both the presence and the absence of metastases, as well as peculiarities of distribution and of growth, are susceptible of a comparatively simple explanation upon the basis of well recognized principles of pathological action. In brief, it was found that, while the tumor cells might be distributed by either the blood stream or the lymphatics, the mode of distribution and the fate of the cells were determined in accordance with the same general principles that are applicable to the distribution and disposal of foreign cells introduced into the animal body. It was pointed out, however, that in applying these principles to tumor metastasis, it was necessary to recognize the fact that tumor cells bear a definite relation to the tissues of the host and that they are living and agressive agents. Hence, the reaction that they arouse differs in some respects from that produced by inert or unorganized foreign material or by living cells of a foreign species. PMID:19868797

Evaluation of arterial impairment after experimental gelatin sponge embolization in a rabbit renal model

International Nuclear Information System (INIS)

Oh, Jung Suk; Lee, Hae Gi; Chun, Ho Jong; Choi, Byung Gil; Choi, Yeong Jin

2015-01-01

Arterial stenosis is a major obstacle for subsequent interventional procedures. We hypothesized that the stenosis is caused by gelatin sponge embolization and performed an experimental study in a rabbit renal model. A total of 24 rabbits were embolized with porcine gelatin sponge particles injected into the renal arteries. Four rabbits were sacrificed on 1 day, 4 days, 1 week, 2 weeks, 3 weeks, and 4 weeks after embolization. Microscopic evaluations were performed on hematoxylin-eosin and smooth muscle actin immunohistochemical stained sections. Gelatin sponge particles were mainly observed in the segmental and interlobar arteries. Transmural inflammation of the embolized arterial wall and mild thickening of the media were observed 1 week after embolization. Resorption of the gelatin sponge and organization of thrombus accompanied by foreign body reactions, were observed from 2 to 4 weeks after embolization. Microscopic images of the 3 weeks group showed vessel lumens filled mostly with organized thrombi, resulting in severe stenosis. Additionally, vessels showed a thickened intima that contained migrating smooth muscle cells and accompanying interruption of the internal elastic lamina. The migrating smooth muscle cells were distributed around the recanalized arterial lumen. Gelatin sponge embolization may induce arterial stenosis by causing organized thrombus and intimal hyperplasia, which consists of migrating smooth muscle cells and intimal collagen deposits.

Evaluation of arterial impairment after experimental gelatin sponge embolization in a rabbit renal model

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Oh, Jung Suk; Lee, Hae Gi; Chun, Ho Jong; Choi, Byung Gil; Choi, Yeong Jin [Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of)

2015-02-15

Arterial stenosis is a major obstacle for subsequent interventional procedures. We hypothesized that the stenosis is caused by gelatin sponge embolization and performed an experimental study in a rabbit renal model. A total of 24 rabbits were embolized with porcine gelatin sponge particles injected into the renal arteries. Four rabbits were sacrificed on 1 day, 4 days, 1 week, 2 weeks, 3 weeks, and 4 weeks after embolization. Microscopic evaluations were performed on hematoxylin-eosin and smooth muscle actin immunohistochemical stained sections. Gelatin sponge particles were mainly observed in the segmental and interlobar arteries. Transmural inflammation of the embolized arterial wall and mild thickening of the media were observed 1 week after embolization. Resorption of the gelatin sponge and organization of thrombus accompanied by foreign body reactions, were observed from 2 to 4 weeks after embolization. Microscopic images of the 3 weeks group showed vessel lumens filled mostly with organized thrombi, resulting in severe stenosis. Additionally, vessels showed a thickened intima that contained migrating smooth muscle cells and accompanying interruption of the internal elastic lamina. The migrating smooth muscle cells were distributed around the recanalized arterial lumen. Gelatin sponge embolization may induce arterial stenosis by causing organized thrombus and intimal hyperplasia, which consists of migrating smooth muscle cells and intimal collagen deposits.

Augmentation of tendon healing with butyric acid-impregnated sutures: biomechanical evaluation in a rabbit model.

Science.gov (United States)

Leek, Bryan T; Tasto, James P; Tibor, Lisa M; Healey, Robert M; Freemont, Anthony; Linn, Michael S; Chase, Derek E; Amiel, David

2012-08-01

Butyric acid (BA) has been shown to be angiogenic and to enhance transcriptional activity in tissue. These properties of BA have the potential to augment biological healing of a repaired tendon. To evaluate this possibility both biomechanically and histologically in an animal tendon repair model. Controlled laboratory study. A rabbit Achilles tendon healing model was used to evaluate the biomechanical strength and histological properties at 6 and 12 weeks after repair. Unilateral tendon defects were created in the middle bundle of the Achilles tendon of each rabbit, which were repaired equivalently with either Ultrabraid BA-impregnated sutures or control Ultrabraid sutures. After 6 weeks, BA-impregnated suture repairs had a significantly increased (P Tendons repaired with BA-impregnated sutures demonstrated improved biomechanical properties at 6 weeks relative to control sutures, suggesting a neoangiogenic mechanism of enhanced healing through an increased myofibroblast presence. These findings demonstrate that a relatively simple alteration of suture material may augment early tendon healing to create a stronger repair construct during this time.

SEMEN QUALITY ASSESSMENT OF NEW ZEALAND WHITE RABBIT BUCKS

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Martyna Błaszczyk

2013-02-01

Full Text Available Rabbits have been extensively used as a model for large animals and humans. All the reproduction techniques employed with farm animals can be performed with the low-cost rabbit model, and certain placental membrane characteristics make them especially relevant for studies of human teratology. The purpose of this study was to assess semen quality of New Zealand White rabbits. The material represents semen samples collected from adult rabbits (n=30. The semen was obtained by means of artificial vagina. All samples were analyzed using CASA Sperm VisionTM system. To assessed spermatozoa morphology (the length and the width of head and tail; presence of abnormal spermatozoa we used QuickPhoto Micro system. Received data were statistically analyzed. Our research showed decrease of semen parameters value after one hour storage in 37°C. Correlation analysis showed negative correlation between presence of spermatozoa with separated flagellum and CASA parameters value e.g. motility, progressive motility, DAP, DCL, DSL, VAP, VCL, VSL, ALH and BCF. From among 3000 analyzed spermatozoa 14.2% posed abnormal forms. We observed negative influence of semen storage on its quality. Also negative correlations between all types of tail defect and motility of spermatozoa were detectedRabbits have been extensively used as a model for large animals and humans. All the reproduction techniques employed with farm animals can be performed with the low-cost rabbit model, and certain placental membrane characteristics make them especially relevant for studies of human teratology. The purpose of this study was to assess semen quality of New Zealand White rabbits. The material represents semen samples collected from adult rabbits (n=30. The semen was obtained by means of artificial vagina. All samples were analyzed using CASA Sperm VisionTM system. To assessed spermatozoa morphology (the length and the width of head and tail; presence of abnormal spermatozoa we used Quick

Correction of rabbit model with mandibular ramus shortening by distraction osteogenesis at condylar neck.

Science.gov (United States)

Meng, Qinggong; Yang, Xuewen; Long, Xing; Li, Jian; Cai, Hengxing

2012-04-01

The rabbit model has been established to mimic the effect of temporomandibular joint (TMJ) arthroplasty of ankylosis, and distraction at the level of the condylar neck is used to elongate the ascending ramus. The histomorphologic changes of TMJ and distraction gap were investigated. The unilateral condyles and articular discs were extirpated, and the experimental mandibular rami were shortened by 5 mm. An embedded distracter was used to restore the height of the mandibular ramus by unilateral condylar neck distraction (0.8 mm daily for 7 days). A total of 12 adult white rabbits were used, 8 in the experimental group and 4 in the control group. Of the 8 rabbits in the experimental group, 4 each were killed at 4 and 8 weeks after completion of distraction. The TMJ and distracted calluses were harvested and processed for radiographic and histologic examination. An open bite was seen in all rabbits postoperatively that had diminished at the end of distraction. The newly formed condyles radiologically showed remodeling, flattening, and sclerosis. The bony transport disc had gradually remodeled to a new condyle that was similar to the original condyle in appearance and structure. The surface of the transport disc was covered with a fibrous tissue. Moreover, the bony regeneration was perfect in the distraction gap. These results suggest that distraction osteogenesis at the condylar neck using the traditional preauricular approach of TMJ surgery, without the additional incision, can be performed concurrently with arthroplasty of TMJ ankylosis at the same region. Copyright © 2012 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

Effects of genipin corneal crosslinking in rabbit corneas.

Science.gov (United States)

Avila, Marcel Y; Narvaez, Mauricio; Castañeda, Juan P

2016-07-01

To evaluate the effect of genipin, a natural crosslinking agent, in rabbit eyes. Department of Ophthalmology, Universidad Nacional de Colombia Centro de Tecnologia Oftalmica, Bogotá, Colombia. Experimental study. Ex vivo rabbit eyes (16; 8 rabbits) were treated with genipin 1.00%, 0.50%, and 0.25% for 5 minutes with a vacuum device to increase corneal permeability. Penetration was evaluated using Scheimpflug pachymetry (Pentacam). In the in vivo model (20 rabbits; 1 eye treated, 1 eye with vehicle), corneas were crosslinked with genipin as described. Corneal curvature, corneal pachymetry, and intraocular pressure (IOP) assessments as well as slitlamp examinations were performed 0, 7, 30, and 60 days after treatment. In the ex vivo model, Scheimpflug pachymetry showed deep penetration in the rabbit corneas with an increase in corneal density and a dose-dependent relationship. Corneal flattening was observed in treated eyes (mean 4.4 diopters ± 0.5 [SD]) compared with the control eyes. Pachymetry and IOP were stable in all evaluations. No eye showed toxicity in the anterior chamber or in the lens. Corneal crosslinking induced by genipin produced significant flattening of the cornea with no toxicity in rabbit eyes. This crosslinking could be useful in the treatment of corneal ectasia and in the modification of corneal curvature. None of the authors has a financial or proprietary interest in any material or method mentioned. Copyright © 2016 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Relationship between aneurysm occlusion and flow diverting device oversizing in a rabbit model.

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Hodis, Simona; Ding, Yong-Hong; Dai, Daying; Lingineni, Ravi; Mut, Fernando; Cebral, Juan; Kallmes, David; Kadirvel, Ramanathan

2016-01-01

Implanted, actual flow diverter pore density is thought to be strongly influenced by proper matching between the device size and parent artery diameter. The objective of this study was to characterize the correlation between device sizing, metal coverage, and the resultant occlusion of aneurysms following flow diverter treatment in a rabbit model. Rabbit saccular aneurysms were treated with flow diverters (iso-sized to proximal parent artery, 0.5 mm oversized, or 1.0 mm oversized, respectively, n=6 for each group). Eight weeks after implantation, the angiographic degree of aneurysm occlusion was graded (complete, near-complete, or incomplete). The ostium of the explanted aneurysm covered with the flow diverter struts was photographed. Based on gross anatomic findings, the metal coverage and pore density at the ostium of the aneurysm were calculated and correlated with the degree of aneurysm occlusion. Angiographic results showed there were no statistically significant differences in aneurysm geometry and occlusion among groups. The mean parent artery diameter to flow diverter diameter ratio was higher in the 1.0 mm oversized group than in the other groups. Neither the percentage metal coverage nor the pore density showed statistically significant differences among groups. Aneurysm occlusion was inversely correlated with the ostium diameter, irrespective of the size of the device implanted. Device sizing alone does not predict resultant pore density or metal coverage following flow diverter implantation in the rabbit aneurysm model. Aneurysm occlusion was not impacted by either metal coverage or pore density, but was inversely correlated with the diameter of the ostium. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Transgenic rabbits as a model organism for production of human clotting factor VIII

International Nuclear Information System (INIS)

Vasicek, D.; Chrenek, P.; Makarevich, A.; Bauer, M.; Jurcik, R.; Suvegova, K.; Rafay, J.; Bulla, J.; Hetenyi, L.; Erickson, J.; Paleyanda, R.K.

2005-01-01

Human clotting factor VIII (hFVIII) is a very complex and large protein whose expression is difficult, as hFVIII requires extensive post-translational modification to be biologically active. This paper reports the generation of transgenic rabbits as a model species for testing the expression of hFVIII in the mammary gland. For micro-injection, a fusion gene construct was used, consisting of 2.5 kb murine whey acidic protein (mWAP) promoter, 7.2 kb cDNA of hFVIII, and 4.6 kb of 3' flanking sequences of the mWAP gene. from 130 micro-injected zygotes transferred into recipients, 30 offspring were delivered. The pups were screened for the transgene by PCR, using DNA isolated from the ear, and results were confirmed by Southern blot analysis. The transgene was identified in one female founder animal, and it was transmitted to the offspring in a Mendelian fashion, thus demonstrating stable integration of the gene construct into the germline of the transgenic rabbits. (author)

Anatomy and Surgical Approaches to the Rabbit Nasal Septum.

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Badran, Karam W; Chang, John C; Kuan, Edward C; Wong, Brian J F

2017-09-01

The rabbit is the primary animal model used to investigate aspects of nasal surgery. Although several studies have used this model, none has provided a comprehensive analysis of the surgical anatomy and techniques used to gain access to the rabbit nasal fossae and septum. To describe and optimize the surgical anatomy and approach to the rabbit nasal vault and septal cartilage. In an ex vivo animal study conducted at an academic medical center, preliminary cadaveric dissections were performed on rabbit head specimens to establish familiarity with relevant anatomy and rehearse various approaches. Live Pasteurella-free New Zealand white rabbits (3.5-4.0 kg) were used to further develop this surgical technique developed here. Access of the nasal vault was gained through a midline nasal dorsum incision and creation of an osteoplastic flap with a drill. Submucosal resection was performed with preservation of the mucoperichondrium. All rabbits were monitored daily for 4 weeks in the postoperative period for signs of infection, pain, and complications. The study was conducted from June 1, 2014, to December 1, 2014. Surgical anatomy and techniques used to gain access to the rabbit nasal vault and harvest septal cartilage. Four Pasteurella-free New Zealand white rabbits (Western Organ Rabbit Co), ranging in age from 9 to 12 months and weighing between 3.5 and 4.0 kg, were used in this study. Initial dissections demonstrated the feasibility of harvesting septal cartilage while preserving the mucoperichondrial envelope. Access to the nasal vault through this 3-osteotomy approach allowed for maximal exposure to the nasal cavity bilaterally while maintaining the integrity of the mucoperichondrium following septal cartilage harvest. The maximum amount of bulk, en bloc, cartilage harvested was 1.0 × 2.5 cm. Following surgical dissection, all animals maintained adequate airway patency and support to midface structures. Furthermore, all specimens preserved the integrity of the

Development of a vivo rabbit ligated intestinal Loop Model for HCMV infection

OpenAIRE

Tang, Jin; Wu, Qiaoxing; Tang, Xinming; Shi, Ruihan; Suo, Jingxia; Huang, Guangping; An, Junqing; Wang, Jingyuan; Yang, Jinling; Hao, Wenzhuo; She, Ruiping; Suo, Xun

2016-01-01

Background Human Cytomegalovirus (HCMV) infections can be found throughout the body, especially in epithelial tissue. Animal model was established by inoculation of HCMV (strain AD-169) or coinoculation with Hepatitis E virus (HEV) into the ligated sacculus rotundus and vermiform appendix in living rabbits. The specimens were collected from animals sacrificed 1 and a half hours after infection. Results The virus was found to be capable of reproducing in these specimens through RT-PCR and West...

Development and characterization of an experimental model of diet-induced metabolic syndrome in rabbit.

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Oscar Julián Arias-Mutis

Full Text Available Metabolic syndrome (MetS has become one of the main concerns for public health because of its link to cardiovascular disease. Murine models have been used to study the effect of MetS on the cardiovascular system, but they have limitations for studying cardiac electrophysiology. In contrast, the rabbit cardiac electrophysiology is similar to human, but a detailed characterization of the different components of MetS in this animal is still needed. Our objective was to develop and characterize a diet-induced experimental model of MetS that allows the study of cardiovascular remodeling and arrhythmogenesis. Male NZW rabbits were assigned to control (n = 15 or MetS group (n = 16, fed during 28 weeks with high-fat, high-sucrose diet. We measured weight, morphological characteristics, blood pressure, glycaemia, standard plasma biochemistry and the metabolomic profile at weeks 14 and 28. Liver histological changes were evaluated using hematoxylin-eosin staining. A mixed model ANOVA or unpaired t-test were used for statistical analysis (P<0.05. Weight, abdominal contour, body mass index, systolic, diastolic and mean arterial pressure increased in the MetS group at weeks 14 and 28. Glucose, triglycerides, LDL, GOT-AST, GOT/GPT, bilirubin and bile acid increased, whereas HDL decreased in the MetS group at weeks 14 and 28. We found a 40% increase in hepatocyte area and lipid vacuoles infiltration in the liver from MetS rabbits. Metabolomic analysis revealed differences in metabolites related to fatty acids, energetic metabolism and microbiota, compounds linked with cardiovascular disease. Administration of high-fat and high-sucrose diet during 28 weeks induced obesity, glucose intolerance, hypertension, non-alcoholic hepatic steatosis and metabolic alterations, thus reproducing the main clinical manifestations of the metabolic syndrome in humans. This experimental model should provide a valuable tool for studies into the mechanisms of cardiovascular

Quantitative T2 mapping evaluation for articular cartilage lesions in a rabbit model of anterior cruciate ligament transection osteoarthritis.

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Wei, Zheng-mao; Du, Xiang-ke; Huo, Tian-long; Li, Xu-bin; Quan, Guang-nan; Li, Tian-ran; Cheng, Jin; Zhang, Wei-tao

2012-03-01

Quantitative T2 mapping has been a widely used method for the evaluation of pathological cartilage properties, and the histological assessment system of osteoarthritis in the rabbit has been published recently. The aim of the study was to investigate the effectiveness of quantitative T2 mapping evaluation for articular cartilage lesions of a rabbit model of anterior cruciate ligament transection (ACLT) osteoarthritis. Twenty New Zealand White (NZW) rabbits were divided into ACLT surgical group and sham operated group equally. The anterior cruciate ligaments of the rabbits in ACLT group were transected, while the joints were closed intactly in sham operated group. Magnetic resonance (MR) examinations were performed on 3.0T MR unit at week 0, week 6, and week 12. T2 values were computed on GE ADW4.3 workstation. All rabbits were killed at week 13, and left knees were stained with Haematoxylin and Eosin. Semiquantitative histological grading was obtained according to the osteoarthritis cartilage histopathology assessment system. Computerized image analysis was performed to quantitate the immunostained collagen type II. The average MR T2 value of whole left knee cartilage in ACLT surgical group ((29.05±12.01) ms) was significantly higher than that in sham operated group ((24.52±7.97) ms) (P=0.024) at week 6. The average T2 value increased to (32.18±12.79) ms in ACLT group at week 12, but remained near the baseline level ((27.66±8.08) ms) in the sham operated group (P=0.03). The cartilage lesion level of left knee in ACLT group was significantly increased at week 6 (P=0.005) and week 12 (PT2 values had positive correlation with histological grading scores, but inverse correlation with optical densities (OD) of type II collagen. This study demonstrated the reliability and practicability of quantitative T2 mapping for the cartilage injury of rabbit ACLT osteoarthritis model.

Pulse sequence optimization for superparamagnetic iron oxide-enhaced MR imaging in the detection of hepatic VX2 tumors in rabbits

International Nuclear Information System (INIS)

Jang, Hyun Jung; Han, Joon Koo; Lee, Kyoung Ho; Kim, Se Hyung; Choi, Byung Ihn; Kim, Tae Kyoung

2003-01-01

The purpose of this experimental study was to determine the optimal pulse sequences for SPIO-enhanced MR imaging in the evaluation of multiple hepatic tumors. Twelve rabbits with multiple VX2 liver tumors underwent SPOI-enhanced MRI using the following nine pulse sequences: TSE T2-weighted imaging (T2W1), TSE proton density-weighted imaging(PDWI), and GRE T2*-weighted imaging (T2*W1) with seven different echo times (TE). Liver-lesion contrast-to-noise ratios (CNRs) were calculated, and images were also assessed qualitatively by two radiologists, who reached a consensus as to lesion conspicuity and imaging artifacts using a four-level scale. By means of pathologic correlation, the sensitivity and positive predictive value of each sequence was calculated. TSE T2W1 and long-TE (35 msec) FLASH T2*W1 showed the highest liver-lesion CNR. The best lesion conspicuity was seen at TSE T2W1 and medium-TE (12 msec) GRE T2*W1. Short TE GRE T2*W1 showed the least imaging artifacts. The four sequences which demonstrated the best sensitivity were medium-TE (12 msec), GRE T2*W1 (FLASH, 84%; FISP, 82%), TSE W2T1 (79%), and TSE PDWI (76%). All nine sequences showed overall high positive predictive value (86-97%), with no statistically significant difference (p>0.05). In terms of image quality and the detection of sensitivity, TSE T2W1 and medium TE (12 msec) GRE T2*W1 were the top two pulse sequences among the various sequences used for no SPIO-enhanced MRI. They are thus considered to be optimal sequences for evaluating multiple malignant hepatic tumors

Autologous bone-marrow mesenchymal stem cell implantation and endothelial function in a rabbit ischemic limb model.

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Shinsuke Mikami

Full Text Available BACKGROUND: The purpose of this study was to determine whether autologous mesenchymal stem cells (MSCs implantation improves endothelial dysfunction in a rabbit ischemic limb model. METHODS: We evaluated the effect of MSC implantation on limb blood flow (LBF responses to acetylcholine (ACh, an endothelium-dependent vasodilator, and sodium nitroprusside (SNP, an endothelium-independent vasodilator, in rabbits with limb ischemia in which cultured MSCs were implanted (n = 20 or saline was injected as a control group (n = 20. LBF was measured using an electromagnetic flowmeter. A total of 10(6 MSCs were implanted into each ischemic limb. RESULTS: Histological sections of ischemic muscle showed that capillary index (capillary/muscle fiber was greater in the MSC implantation group than in the control group. Laser Doppler blood perfusion index was significantly increased in the MSC implantation group compared with that in the control group. LBF response to ACh was greater in the MSC group than in the control group. After administration of N(G-nitro-L-arginine, a nitric oxide synthase inhibitor, LBF response to ACh was similar in the MSC implantation group and control group. Vasodilatory effects of SNP in the two groups were similar. CONCLUSIONS: These findings suggest that MSC implantation induces angiogenesis and augments endothelium-dependent vasodilation in a rabbit ischemic model through an increase in nitric oxide production.

Variable effects of radiological contrast media on thrombus growth in a rabbit jugular vein thrombosis model

NARCIS (Netherlands)

Levi, M. [=Marcel M.; Biemond, B. J.; Sturk, A.; Hoek, J.; ten Cate, J. W.

1991-01-01

We studied the effect of an ionic high osmolar contrast medium (Ioxitalamate), an ionic low osmolar contrast medium (Ioxaglate) and various nonionic low osmolar contrast media (Iopamidol, Iopromide and Iohexol) on thrombus growth in a rabbit jugular vein thrombosis model. Thrombus growth was

Rabbit model of intervertebral disc degeneration by external compression device characterized by X-ray, MRI, histology, and cell viability

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Ismail Ismail

2006-12-01

Full Text Available Appropriate experimental animal models, which mimic the degenerative process occurring in human intervertebral disc (IVD breakdown and can be used for new treatment studies such as tissue engineering or disc distraction are lacking. We studied the external compression device that used by Kroeber et al to create intervertebral disc degeneration in rabbit model characterized by X-ray, MRI, Histology, and Cell Viability. Ten NZW rabbit were randomly assigned to one of five groups. Intervertebral disc VL4-L5 are compressed using an external loading device, 1.9 MPa. First group rabbit are loaded for 14 days, second loaded for 28 days, thirth group are loaded for 14 days, and unloaded for 14 days, fourth group loaded for 28 days and unloaded for 28 days. The fifth group, rabbits underwent a sham operation. Additional, rabbits were used as sample for cell viability study. In disc height : sample in group one have biggest decreasing of disc height, that is 23.9 unit. In MRI assessment, the worst grade is grade 3. In histological score, the worst group is group three (58.69, and the best is group 4 (45.69. Group one have the largest dead cell, that are 403.5, and the smallest is group four (124.75. Trypan blue staining showed that group four have better viable cell (91.1 compare than group three (86.4. The study conclude disc degeneration can be created by external axial loading for 14 days in rabbit intervertebral disc. Duration of 28 days unloading gave better result for cells to recover. (Med J Indones 2006; 15:199-207  Normal 0 false false false EN-US X-NONE X-NONE MicrosoftInternetExplorer4 Keywords: Rabbit model –intervertebral disc degeneration- external compression device-X-ray, MRI, Histology, and Cell viabilty /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso

Comparison of rat and rabbit embryo-fetal developmental ...

Science.gov (United States)

Regulatory non-clinical safety testing of human pharmaceutical compounds typically requires embryo fetal developmental toxicity (EFDT) testing in two species, (one rodent and one non-rodent, usually the rat and the rabbit). The question has been raised whether under some conditions EFDT testing could be limited to one species, or whether the need for testing in a second species could be decided on a case by case basis. As part of an RIVM/CBG-MEB/HESI/US EPA consortium initiative, we built and queried a database of 379 EFDT studies conducted for marketed and non-marketed pharmaceutical compounds. The animal models (rat and rabbit) were assessed for their potential for adverse developmental and maternal outcomes. The database was analyzed for the prevalence of EFDT incidence and the nature and severity of adverse findings in the two species. Some manifestation of EFDT in either one or both species (rat and rabbit) was demonstrated for 282 compounds (74%), and EFDT was detected in only one species (rat or rabbit) in almost a third (31%, 118 compounds), with approximately 58% rat and 42% rabbit studies identifying an EFDT signal among the 379 compounds tested. For 24 compounds (6%), fetal malformations were observed in one species (rat or rabbit) in the absence of any EFDT in the second species. In general, growth retardation, fetal variations, and malformations were more prominent in the rat, whereas embryo-fetal death was observed more often in the rabbit. Discor

Avaliação da área de melanomas amelanóticos de coróide em coelhos: modelo matemático An assessment of rabbit's choroidal amelanotic melanomas area: mathematical model

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Ayrton Roberto Branco Ramos

2002-09-01

Full Text Available Objetivo: Os métodos terapêuticos para o tratamento dos melanomas de coróide incluem a observação, a radioterapia, a cirurgia e a laserterapia. Para acompanhamento do crescimento tumoral, há necessidade de documentação e medida do tamanho desses tumores. O objetivo deste estudo é apresentar um modelo matemático simples e de baixo custo, para medida de áreas desses tumores do fundo de olho. Métodos: Utilizaram-se 25 olhos de coelhos pigmentados. Fragmentos de melanomas amelanóticos de hamster foram implantados cirurgicamente no espaço supracoroideo dos olhos dos animais. Quando os tumores atingiram 3 a 4 diâmetros papilares de tamanho realizaram-se as retinografias e angiografias fluorescentes com retinógrafo sem Imaginet, com foco fixo. Por meio de cálculos matemáticos verificaram-se as áreas reais dos tumores. Resultados: Foi possível verificar as áreas reais dos tumores e na análise da comparação dos valores das médias obtidas para os tumores, verificou-se que não existiu diferença estatisticamente significativa entre eles (p= 0,717. Conclusões: Concluiu-se neste estudo, que com o uso de retinógrafo sem Imaginet, foi possível medir com acurácia e segurança, por meio de cálculo matemático, a área de melanomas amelanóticos de hamster implantados no espaço supracoroídeo de coelhos.Purpose: Methods of management for choroidal melanomas include basically observation, radiotherapy, surgery, and laser therapy. A reliable measure of the size of the tumor is very important to follow tumor growth. The purpose of this experimental study is to verify the reliability of a low-cost mathematical model to measure areas of tumors of the fundus. Methods: Twenty-five eyes of pigmented rabbits were used in this study. Experimental Greene hamster amelanotic choroidal melanomas were implanted into the suprachoroidal space. When the tumors reached 3 to 4 papillary diameters, we performed retinography and fluorescein angiograms

Monochromatic Spectral Computed Tomography with Low Iodine Concentration Contrast Medium in a Rabbit VX2 Liver Model:: Investigation of Image Quality and Detection Rate.

Science.gov (United States)

Zhou, Yue; Xu, Han; Hou, Ping; Dong, Jun Q; Wang, Ming Y; Gao, Jian B

2016-04-01

This study aimed to validate the feasibility of using virtual monochromatic spectral computed tomography (CT) with isotonic low iodine concentration contrast medium for VX2 hepatic tumors. Sixty New Zealand white rabbits with implanted VX2 hepatic tumors underwent two-phase contrast-enhanced spectral CT imaging on the 14th day after tumor implantation. They were randomly divided into groups A, B, and C, with 20 rabbits each (group A: 270 mg I/mL, monochromatic spectral images; group B: 370 mg I/mL, conventional 120 kVp images, 100% filtered back projection [FBP]; group C: 270 mg I/mL, conventional 120 kVp images, 100% FBP). Group A was further divided into two subgroups (subgroup A1: 100% FBP; subgroup A2: 50% FBP + 50% adaptive statistical iterative reconstruction). Objective evaluation (signal-to-noise ratio [SNR], contrast-to-noise ratio [CNR], and image noise), subjective rating score (image noise score, anatomical details score, overall image quality score, and lesion conspicuity score), CT dose index volume, and dose length product were compared between groups during two-phase contrast enhancement. The detection rates of the four groups were calculated as percentages. Image noise (SNR and CNR) among the four groups was statistically significant (P noise in group A2 was lower than in group A1, but higher than that in groups B and C (P noise score of group A2 was higher than that of the other three groups. In terms of the anatomic details score, the overall image quality score, and the lesion conspicuity score, the images of group A2 were superior to that of groups A1 and C. For hepatic tumor diameters more than or equal to 1.0 cm and less than 3.0 cm, group A achieved a higher detection rate than groups B and C. The CT dose index volume, dose length product, and effective dose in group A were significantly lower than that in groups B and C (P noise, increase detection rate for small tumors, and decrease radiation dose and iodine load in

Osteochondral repair in the rabbit model utilizing bilayered, degradable oligo(poly(ethylene glycol) fumarate) hydrogel scaffolds.

NARCIS (Netherlands)

Holland, T.A.; Bodde, E.W.H.; Baggett, L.S.; Tabata, Y.; Mikos, A.G.; Jansen, J.A.

2005-01-01

In this study, hydrogel scaffolds, based on the polymer oligo(poly(ethylene glycol) fumarate) (OPF), were implanted into osteochondral defects in the rabbit model. Scaffolds consisted of two layers-a bottom, bone forming layer and a top, cartilage forming layer. Three scaffold formulations were

Experimental atheromatous plaque imaging with 99mTc labelled low density lipoproteins in rabbit

International Nuclear Information System (INIS)

Wang Quanshi; Chen Yu; Wu Chunshan; Zhang Yijin; Liu Dexuan

1996-01-01

Atheromatous plaque imaging with 99m Tc labeled low density lipoproteins ( 99m Tc-LDL) were evaluated in rabbits for its clinical prospect. The 99m Tc-LDL atheromatous plaque imaging were performed in 9 rabbit models of atherosclerosis and 4 controls. The imagings were compared with autoradiographic and pathological results. The rabbit models of atherosclerosis by high cholesterol and high fat diet were successful in 100%. The atheromatous plaques well visualized in 8 of 9 rabbit models 24 hours after injection. The site and density of radioactive accumulation was closely correlated in autoradiography also. There was no radioactive spot in 4 controls. 99m Tc-LDL imaging may have a significant value for the diagnosis of atherosclerosis

Selected HIV-1 Env trimeric formulations act as potent immunogens in a rabbit vaccination model.

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Leo Heyndrickx

Full Text Available BACKGROUND: Ten to 30% of HIV-1 infected subjects develop broadly neutralizing antibodies (bNAbs during chronic infection. We hypothesized that immunizing rabbits with viral envelope glycoproteins (Envs from these patients may induce bNAbs, when formulated as a trimeric protein and in the presence of an adjuvant. METHODS: Based on in vitro neutralizing activity in serum, patients with bNAbs were selected for cloning of their HIV-1 Env. Seven stable soluble trimeric gp140 proteins were generated from sequences derived from four adults and two children infected with either clade A or B HIV-1. From one of the clade A Envs both the monomeric and trimeric Env were produced for comparison. Rabbits were immunized with soluble gp120 or trimeric gp140 proteins in combination with the adjuvant dimethyl dioctadecyl ammonium/trehalose dibehenate (CAF01. Env binding in rabbit immune serum was determined using ELISAs based on gp120-IIIB protein. Neutralizing activity of IgG purified from rabbit immune sera was measured with the pseudovirus-TZMbl assay and a PBMC-based neutralization assay for selected experiments. RESULTS: It was initially established that gp140 trimers induce better antibody responses over gp120 monomers and that the adjuvant CAF01 was necessary for such strong responses. Gp140 trimers, based on HIV-1 variants from patients with bNAbs, were able to elicit both gp120IIIB specific IgG and NAbs to Tier 1 viruses of different subtypes. Potency of NAbs closely correlated with titers, and an gp120-binding IgG titer above a threshold of 100,000 was predictive of neutralization capability. Finally, peptide inhibition experiments showed that a large fraction of the neutralizing IgG was directed against the gp120 V3 region. CONCLUSIONS: Our results indicate that the strategy of reverse immunology based on selected Env sequences is promising when immunogens are delivered as stabilized trimers in CAF01 adjuvant and that the rabbit is a valuable model

Selected HIV-1 Env trimeric formulations act as potent immunogens in a rabbit vaccination model.

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Heyndrickx, Leo; Stewart-Jones, Guillaume; Jansson, Marianne; Schuitemaker, Hanneke; Bowles, Emma; Buonaguro, Luigi; Grevstad, Berit; Vinner, Lasse; Vereecken, Katleen; Parker, Joe; Ramaswamy, Meghna; Biswas, Priscilla; Vanham, Guido; Scarlatti, Gabriella; Fomsgaard, Anders

2013-01-01

Ten to 30% of HIV-1 infected subjects develop broadly neutralizing antibodies (bNAbs) during chronic infection. We hypothesized that immunizing rabbits with viral envelope glycoproteins (Envs) from these patients may induce bNAbs, when formulated as a trimeric protein and in the presence of an adjuvant. Based on in vitro neutralizing activity in serum, patients with bNAbs were selected for cloning of their HIV-1 Env. Seven stable soluble trimeric gp140 proteins were generated from sequences derived from four adults and two children infected with either clade A or B HIV-1. From one of the clade A Envs both the monomeric and trimeric Env were produced for comparison. Rabbits were immunized with soluble gp120 or trimeric gp140 proteins in combination with the adjuvant dimethyl dioctadecyl ammonium/trehalose dibehenate (CAF01). Env binding in rabbit immune serum was determined using ELISAs based on gp120-IIIB protein. Neutralizing activity of IgG purified from rabbit immune sera was measured with the pseudovirus-TZMbl assay and a PBMC-based neutralization assay for selected experiments. It was initially established that gp140 trimers induce better antibody responses over gp120 monomers and that the adjuvant CAF01 was necessary for such strong responses. Gp140 trimers, based on HIV-1 variants from patients with bNAbs, were able to elicit both gp120IIIB specific IgG and NAbs to Tier 1 viruses of different subtypes. Potency of NAbs closely correlated with titers, and an gp120-binding IgG titer above a threshold of 100,000 was predictive of neutralization capability. Finally, peptide inhibition experiments showed that a large fraction of the neutralizing IgG was directed against the gp120 V3 region. Our results indicate that the strategy of reverse immunology based on selected Env sequences is promising when immunogens are delivered as stabilized trimers in CAF01 adjuvant and that the rabbit is a valuable model for HIV vaccine studies.

Tumor-associated proteins in rat submandibular gland induced by DMBA and irradiation

International Nuclear Information System (INIS)

Oh, Sung Ook; Choi, Soon Chul; Park, Tae Won; You, Dong Soo

1997-01-01

This study was performed in order to identify changes of the plasma membrane proteins in rat submandibular gland tumors induced by 7,12-dimethylbenz[a]anthracene [DMBA] and X-irradiation. Two kinds of tumor associated membrane proteins (protein A and B) were isolated with 3 M KCl extraction from rat submandibular gland tumors induced by DMBA and X-irradiation. To identify their antigenicities, immunoelectrophoresis and double immunodiffusion was carried out with various proteins extracted from liver, heart, skin and pancreas of adult rats and from embryonic liver, heart and skin. The rabbit antisera against the protein A did not cross-react with any of the proteins extracted from the above mentioned tissues, suggesting that protein A might be tumor specific antigen. However, the rabbit antisera against protein B was precipitated with proteins extracted from the liver of adult and embryonic rats. Polyacrylamide gel electrophoresis of these two proteins (A and B) showed that protein A was a dimer with molecular weights of 69,000 and 35,000 dalton, whereas protein B was a monomer with molecular weight of 50,000 dalton.

Repair of Achilles tendon defect with autologous ASCs engineered tendon in a rabbit model.

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Deng, Dan; Wang, Wenbo; Wang, Bin; Zhang, Peihua; Zhou, Guangdong; Zhang, Wen Jie; Cao, Yilin; Liu, Wei

2014-10-01

Adipose derived stem cells (ASCs) are an important cell source for tissue regeneration and have been demonstrated the potential of tenogenic differentiation in vitro. This study explored the feasibility of using ASCs for engineered tendon repair in vivo in a rabbit Achilles tendon model. Total 30 rabbits were involved in this study. A composite tendon scaffold composed of an inner part of polyglycolic acid (PGA) unwoven fibers and an outer part of a net knitted with PGA/PLA (polylactic acid) fibers was used to provide mechanical strength. Autologous ASCs were harvested from nuchal subcutaneous adipose tissues and in vitro expanded. The expanded ASCs were harvested and resuspended in culture medium and evenly seeded onto the scaffold in the experimental group, whereas cell-free scaffolds served as the control group. The constructs of both groups were cultured inside a bioreactor under dynamic stretch for 5 weeks. In each of 30 rabbits, a 2 cm defect was created on right side of Achilles tendon followed by the transplantation of a 3 cm cell-seeded scaffold in the experimental group of 15 rabbits, or by the transplantation of a 3 cm cell-free scaffold in the control group of 15 rabbits. Animals were sacrificed at 12, 21 and 45 weeks post-surgery for gross view, histology, and mechanical analysis. The results showed that short term in vitro culture enabled ASCs to produce matrix on the PGA fibers and the constructs showed tensile strength around 50 MPa in both groups (p > 0.05). With the increase of implantation time, cell-seeded constructs gradually form neo-tendon and became more mature at 45 weeks with histological structure similar to that of native tendon and with the presence of bipolar pattern and D-periodic structure of formed collagen fibrils. Additionally, both collagen fibril diameters and tensile strength increased continuously with significant difference among different time points (p tendon tissue with fibril structure observable only at 45 weeks

Reflection on design and testing of pancreatic alpha-amylase inhibitors: an in silico comparison between rat and rabbit enzyme models

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Khalil-Moghaddam Shiva

2012-11-01

Full Text Available Abstract Background Inhibitors of pancreatic alpha-amylase are potential drugs to treat diabetes and obesity. In order to find compounds that would be effective amylase inhibitors, in vitro and in vivo models are usually used. The accuracy of models is limited, but these tools are nonetheless valuable. In vitro models could be used in large screenings involving thousands of chemicals that are tested to find potential lead compounds. In vivo models are still used as preliminary mean of testing compounds behavior in the whole organism. In the case of alpha-amylase inhibitors, both rats and rabbits could be chosen as in vivo models. The question was which animal could present more accuracy with regard to its pancreatic alpha-amylase. Results As there is no crystal structure of these enzymes, a molecular modeling study was done in order to compare the rabbit and rat enzymes with the human one. The overall result is that rabbit enzyme could probably be a better choice in this regard, but in the case of large ligands, which could make putative interactions with the −4 subsite of pancreatic alpha-amylase, interpretation of results should be made cautiously. Conclusion Molecular modeling tools could be used to choose the most suitable model enzyme that would help to identify new enzyme inhibitors. In the case of alpha-amylase, three-dimensional structures of animal enzymes show differences with the human one which should be taken into account when testing potential new drugs.

Brain Tumor Segmentation Using a Generative Model with an RBM Prior on Tumor Shape

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Agn, Mikael; Puonti, Oula; Rosenschöld, Per Munck af

2016-01-01

In this paper, we present a fully automated generative method for brain tumor segmentation in multi-modal magnetic resonance images. The method is based on the type of generative model often used for segmenting healthy brain tissues, where tissues are modeled by Gaussian mixture models combined...... the use of the intensity information in the training images. Experiments on public benchmark data of patients suffering from low- and high-grade gliomas show that the method performs well compared to current state-of-the-art methods, while not being tied to any specific imaging protocol....... with a spatial atlas-based tissue prior. We extend this basic model with a tumor prior, which uses convolutional restricted Boltzmann machines (cRBMs) to model the shape of both tumor core and complete tumor, which includes edema and core. The cRBMs are trained on expert segmentations of training images, without...

Spherical Cancer Models in Tumor Biology

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Louis-Bastien Weiswald

2015-01-01

Full Text Available Three-dimensional (3D in vitro models have been used in cancer research as an intermediate model between in vitro cancer cell line cultures and in vivo tumor. Spherical cancer models represent major 3D in vitro models that have been described over the past 4 decades. These models have gained popularity in cancer stem cell research using tumorospheres. Thus, it is crucial to define and clarify the different spherical cancer models thus far described. Here, we focus on in vitro multicellular spheres used in cancer research. All these spherelike structures are characterized by their well-rounded shape, the presence of cancer cells, and their capacity to be maintained as free-floating cultures. We propose a rational classification of the four most commonly used spherical cancer models in cancer research based on culture methods for obtaining them and on subsequent differences in sphere biology: the multicellular tumor spheroid model, first described in the early 70s and obtained by culture of cancer cell lines under nonadherent conditions; tumorospheres, a model of cancer stem cell expansion established in a serum-free medium supplemented with growth factors; tissue-derived tumor spheres and organotypic multicellular spheroids, obtained by tumor tissue mechanical dissociation and cutting. In addition, we describe their applications to and interest in cancer research; in particular, we describe their contribution to chemoresistance, radioresistance, tumorigenicity, and invasion and migration studies. Although these models share a common 3D conformation, each displays its own intrinsic properties. Therefore, the most relevant spherical cancer model must be carefully selected, as a function of the study aim and cancer type.

The Rabbit Stream Cipher

DEFF Research Database (Denmark)

Boesgaard, Martin; Vesterager, Mette; Zenner, Erik

2008-01-01

The stream cipher Rabbit was first presented at FSE 2003, and no attacks against it have been published until now. With a measured encryption/decryption speed of 3.7 clock cycles per byte on a Pentium III processor, Rabbit does also provide very high performance. This paper gives a concise...... description of the Rabbit design and some of the cryptanalytic results available....

Tyrosine-derived polycarbonate scaffolds for bone regeneration in a rabbit radius critical-size defect model

International Nuclear Information System (INIS)

Kim, Jinku; McBride, Sean; Donovan, Amy; Hollinger, Jeffrey O; Darr, Aniq; Magno, Maria Hanshella R

2015-01-01

The aim of the study was to determine bone regeneration in a rabbit radius critical-size defect (CSD) model using a specific polymer composition (E1001(1k)) from a library of tyrosine-derived polycarbonate scaffolds coated with a calcium phosphate (CP) formulation (E1001(1k) + CP) supplemented with recombinant human bone morphogenetic protein-2 (rhBMP-2). Specific doses of rhBMP-2 (0, 17, and 35 μg/scaffold) were used. E1001(1k) + CP scaffolds were implanted in unilateral segmental defects (15 mm length) in the radial diaphyses of New Zealand White rabbits. At 4 and 8 weeks post-implantation, bone regeneration was determined using micro-computed tomography (µCT), histology, and histomorphometry. The quantitative outcome data suggest that E1001(1k) + CP scaffolds with rhBMP-2 were biocompatible and promoted bone regeneration in segmental bone defects. Histological examination of the implant sites showed that scaffolds made of E1001(1k) + CP did not elicit adverse cellular or tissue responses throughout test periods up to 8 weeks. Noteworthy is that the incorporation of a very small amount of rhBMP-2 into the scaffolds (as low as 17 μg/defect site) promoted significant bone regeneration compared to scaffolds consisting of E1001(1k) + CP alone. This finding indicates that E1001(1k) + CP may be an effective platform for bone regeneration in a critical size rabbit radius segmental defect model, requiring only a minimal dose of rhBMP-2. (paper)

Bladder urine oxygen tension for assessing renal medullary oxygenation in rabbits: experimental and modeling studies

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Sgouralis, Ioannis; Kett, Michelle M.; Ow, Connie P. C.; Abdelkader, Amany; Layton, Anita T.; Gardiner, Bruce S.; Smith, David W.; Lankadeva, Yugeesh R.

2016-01-01

Oxygen tension (Po2) of urine in the bladder could be used to monitor risk of acute kidney injury if it varies with medullary Po2. Therefore, we examined this relationship and characterized oxygen diffusion across walls of the ureter and bladder in anesthetized rabbits. A computational model was then developed to predict medullary Po2 from bladder urine Po2. Both intravenous infusion of [Phe2,Ile3,Orn8]-vasopressin and infusion of NG-nitro-l-arginine reduced urinary Po2 and medullary Po2 (8–17%), yet had opposite effects on renal blood flow and urine flow. Changes in bladder urine Po2 during these stimuli correlated strongly with changes in medullary Po2 (within-rabbit r2 = 0.87–0.90). Differences in the Po2 of saline infused into the ureter close to the kidney could be detected in the bladder, although this was diminished at lesser ureteric flow. Diffusion of oxygen across the wall of the bladder was very slow, so it was not considered in the computational model. The model predicts Po2 in the pelvic ureter (presumed to reflect medullary Po2) from known values of bladder urine Po2, urine flow, and arterial Po2. Simulations suggest that, across a physiological range of urine flow in anesthetized rabbits (0.1–0.5 ml/min for a single kidney), a change in bladder urine Po2 explains 10–50% of the change in pelvic urine/medullary Po2. Thus, it is possible to infer changes in medullary Po2 from changes in urinary Po2, so urinary Po2 may have utility as a real-time biomarker of risk of acute kidney injury. PMID:27385734

Long-term reorganization of structural brain networks in a rabbit model of intrauterine growth restriction.

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Batalle, Dafnis; Muñoz-Moreno, Emma; Arbat-Plana, Ariadna; Illa, Miriam; Figueras, Francesc; Eixarch, Elisenda; Gratacos, Eduard

2014-10-15

Characterization of brain changes produced by intrauterine growth restriction (IUGR) is among the main challenges of modern fetal medicine and pediatrics. This condition affects 5-10% of all pregnancies and is associated with a wide range of neurodevelopmental disorders. Better understanding of the brain reorganization produced by IUGR opens a window of opportunity to find potential imaging biomarkers in order to identify the infants with a high risk of having neurodevelopmental problems and apply therapies to improve their outcomes. Structural brain networks obtained from diffusion magnetic resonance imaging (MRI) is a promising tool to study brain reorganization and to be used as a biomarker of neurodevelopmental alterations. In the present study this technique is applied to a rabbit animal model of IUGR, which presents some advantages including a controlled environment and the possibility to obtain high quality MRI with long acquisition times. Using a Q-Ball diffusion model, and a previously published rabbit brain MRI atlas, structural brain networks of 15 IUGR and 14 control rabbits at 70 days of age (equivalent to pre-adolescence human age) were obtained. The analysis of graph theory features showed a decreased network infrastructure (degree and binary global efficiency) associated with IUGR condition and a set of generalized fractional anisotropy (GFA) weighted measures associated with abnormal neurobehavior. Interestingly, when assessing the brain network organization independently of network infrastructure by means of normalized networks, IUGR showed increased global and local efficiencies. We hypothesize that this effect could reflect a compensatory response to reduced infrastructure in IUGR. These results present new evidence on the long-term persistence of the brain reorganization produced by IUGR that could underlie behavioral and developmental alterations previously described. The described changes in network organization have the potential to be used

Hemodynamic Changes Caused by Flow Diverters in Rabbit Aneurysm Models: Comparison of Virtual and Realistic FD Deployments Based on Micro-CT Reconstruction

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Fang, Yibin; Yu, Ying; Cheng, Jiyong; Wang, Shengzhang; Wang, Kuizhong; Liu, Jian-Min; Huang, Qinghai

2013-01-01

Adjusting hemodynamics via flow diverter (FD) implantation is emerging as a novel method of treating cerebral aneurysms. However, most previous FD-related hemodynamic studies were based on virtual FD deployment, which may produce different hemodynamic outcomes than realistic (in vivo) FD deployment. We compared hemodynamics between virtual FD and realistic FD deployments in rabbit aneurysm models using computational fluid dynamics (CFD) simulations. FDs were implanted for aneurysms in 14 rabbits. Vascular models based on rabbit-specific angiograms were reconstructed for CFD studies. Real FD configurations were reconstructed based on micro-CT scans after sacrifice, while virtual FD configurations were constructed with SolidWorks software. Hemodynamic parameters before and after FD deployment were analyzed. According to the metal coverage (MC) of implanted FDs calculated based on micro-CT reconstruction, 14 rabbits were divided into two groups (A, MC >35%; B, MC 0.05). The normalized mean WSS in Group A after realistic FD implantation was significantly lower than that of Group B. All parameters in Group B exhibited no significant difference between realistic and virtual FDs. This study confirmed MC-correlated differences in hemodynamic parameters between realistic and virtual FD deployment. PMID:23823503

In silico modeling for tumor growth visualization.

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Jeanquartier, Fleur; Jean-Quartier, Claire; Cemernek, David; Holzinger, Andreas

2016-08-08

Cancer is a complex disease. Fundamental cellular based studies as well as modeling provides insight into cancer biology and strategies to treatment of the disease. In silico models complement in vivo models. Research on tumor growth involves a plethora of models each emphasizing isolated aspects of benign and malignant neoplasms. Biologists and clinical scientists are often overwhelmed by the mathematical background knowledge necessary to grasp and to apply a model to their own research. We aim to provide a comprehensive and expandable simulation tool to visualizing tumor growth. This novel Web-based application offers the advantage of a user-friendly graphical interface with several manipulable input variables to correlate different aspects of tumor growth. By refining model parameters we highlight the significance of heterogeneous intercellular interactions on tumor progression. Within this paper we present the implementation of the Cellular Potts Model graphically presented through Cytoscape.js within a Web application. The tool is available under the MIT license at https://github.com/davcem/cpm-cytoscape and http://styx.cgv.tugraz.at:8080/cpm-cytoscape/ . In-silico methods overcome the lack of wet experimental possibilities and as dry method succeed in terms of reduction, refinement and replacement of animal experimentation, also known as the 3R principles. Our visualization approach to simulation allows for more flexible usage and easy extension to facilitate understanding and gain novel insight. We believe that biomedical research in general and research on tumor growth in particular will benefit from the systems biology perspective.

Effect of premedication with subcutaneous adrenaline on the pharmacokinetics and immunogenicity of equine whole IgG antivenom in a rabbit model.

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Herrera, María; Sánchez, Melvin; Machado, Anderson; Ramírez, Nils; Vargas, Mariángela; Villalta, Mauren; Sánchez, Andrés; Segura, Álvaro; Gómez, Aarón; Solano, Gabriela; Gutiérrez, José María; León, Guillermo

2017-06-01

Subcutaneous administration of a low dose of adrenaline is used to prevent the early adverse reactions (EARs) induced by snake antivenoms. We used a rabbit model to study the effect of premedication with adrenaline on the potential of antivenoms to exert therapeutic effects and to induce late adverse reactions. We found that premedication with adrenaline did not change the heart rate or blood pressure of normal rabbits, but reduced the rise in temperature in rabbits previously sensitized with antivenom. Pharmacokinetic studies suggest that premedication with adrenaline does not affect the ability of the antivenom to exert the initial control of envenomation nor the susceptibility of rabbits to develop recurrence of antigenemia and envenomation. Our results also indicate that it is unlikely that premedication with adrenaline decreases the incidence of late reactions induced by the antivenom administration, although it reduces the extent of early reactions. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Apoptosis of rabbit retinal cell after eyeball rupture.

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Tian, Xue-Min; Zhu, Yu

2013-04-13

To establish rabbit eyeball rupture model by air gun in order to observe and analyze the early injury condition and reasons of retinal cell after eyeball rupture. Forty eight healthy rabbits were randomly divided into control group and 1, 3, 6, 12 and 24 h after injury groups. After anesthesia, the rabbit eyeball rupture model was established by air gun. Then the early pathological changes of rabbit retina were observed, and apoptotic index (AI), oncosis index (OI), the relationship between the expression amounts of apoptosis-related genes and AI were analyzed. Obvious pathological lesion appeared in retina 6 h after injury. Irreversible damage occurred 12-24 h after injury. The results of AI and OI indicated that the OI peak appeared 6 h after injury and then gradually declined, while the AI increased with the prolongation of time, and the AI was higher than OI in 12 h after injury. Immunohistochemical results indicated that there was no obvious bcl-2 protein expression change. Compared with the control group and the 3, 6, 12 and 24 h after the injury groups, the expressions of p53 and Caspase-3 were significantly improved and peaked at 12 h (Peyeball rupture. Copyright © 2013 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Radiolabeling, biodistribution and tumor imaging of stealth liposomes containing methotrexate

International Nuclear Information System (INIS)

Subramanian, N; Arulsudar, N; Chuttani, K; Mishra, P; Sharma, R.K; Murthy, R.S.R

2003-01-01

To study the utility of sterically stabilized liposomes (stealth liposomes) in tumor scintigraphy by studying its biodistribution and accumulation in target tissue after radiolabeling with Technetium-99m (99mTC). Conventional and Stealth liposomes were prepared by lipid film hydration method using methotrexate as model anticancer drug. Radiolabeling of the liposomes was carried out by direct labeling using reduced 99mTc. Experimental conditions for maximum labeling yield were optimized. The stability studies were carried out to check binding strength of the radiolabeled complexes. The blood kinetic study was carried out in rabbits after giving the labeled complex by intravenous administration through ear vein. The biodistribution studies were carried out in the Ehrlich ascites tumor (EAT) bearing mice after intravenous administration through tail vein, showed prolonged circulation in blood and significant increase in the accumulation in tumor for the sterically stabilized liposomes compared to the conventional liposomes. The gamma scintigraphic image shows the distribution of the stealth liposomes in liver, spleen, kidney and tumor. The study gives precise idea about the use of stealth liposomes in tumor scintigraphy and organ distribution studies (Au)

The cytolethal distending toxin of Haemophilus ducreyi aggravates dermal lesions in a rabbit model of chancroid.

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Wising, Catharina; Mölne, Lena; Jonsson, Ing-Marie; Ahlman, Karin; Lagergård, Teresa

2005-05-01

Haemophilus ducreyi, the etiologic agent of the sexually transmitted disease chancroid, produces a cytolethal distending toxin (HdCDT) that inhibits cultured cell proliferation, leading to cell death. A rabbit model of dermal infection was used to investigate the roles of H. ducreyi bacteria and HdCDT in the development, clinical appearance, and persistence of infection. A non-toxin producing H. ducreyi strain, and for comparison purposes a non-capsulated Haemophilus influenzae strain, were inoculated intradermally, with and without co-administration of purified HdCDT. Co-administration of HdCDT resulted in significant aggravation of H. ducreyi-induced inflammatory lesions, and development of ulcers in rabbit skin. Less pronounced inflammatory lesions and lack of epithelial eruption were observed after inoculation with H. influenzae. Histopathological sections of the H. ducreyi-induced lesions, in both the presence and absence of HdCDT, showed dense infiltrates of the same type inflammatory cells, with the exception of a prominent endothelial cell proliferation noted in sections from lesions caused by H. ducreyi and toxin. Signs of chronic inflammation with involvement of T cells, macrophages, eosinophils, and granuloma formation were observed after H. ducreyi inoculation both with and without toxin. In conclusion, H. ducreyi causes a pronounced, chronic inflammation with involvement of T cells and macrophages, and in combination with HdCDT production of ulcers in the rabbit model. These pathogenic mechanisms may promote the development and persistence of chancroid ulcers.

Distribution and prevalence of the Australian non-pathogenic rabbit calicivirus is correlated with rainfall and temperature.

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June Liu

Full Text Available BACKGROUND: Australia relies heavily on rabbit haemorrhagic disease virus (RHDV for the biological control of introduced European wild rabbits Oryctolagus cuniculus, which are significant economic and environmental pests. An endemic non-pathogenic rabbit calicivirus termed RCV-A1 also occurs in wild rabbits in Australian and provides partial protection against lethal RHDV infection, thus interfering with effective rabbit control. Despite its obvious importance for rabbit population management, little is known about the epidemiology of this benign rabbit calicivirus. METHODS: We determined the continent-wide distribution and prevalence of RCV-A1 by analysing 1,805 serum samples from wild rabbit populations at 78 sites across Australia for the presence of antibodies to RCV-A1 using a serological test that specifically detects RCV-A1 antibodies and does not cross-react with co-occurring RHDV antibodies. We also investigated possible correlation between climate variables and prevalence of RCV-A1 by using generalised linear mixed effect models. RESULTS: Antibodies to RCV-A1 were predominantly detected in rabbit populations in cool, high rainfall areas of the south-east and south-west of the continent. There was strong support for modelling RCV-A1 prevalence as a function of average annual rainfall and minimum temperature. The best ranked model explained 26% of the model structural deviance. According to this model, distribution and prevalence of RCV-A1 is positively correlated with periods of above average rainfall and negatively correlated with periods of drought. IMPLICATIONS: Our statistical model of RCV-A1 prevalence will greatly increase our understanding of RCV-A1 epidemiology and its interaction with RHDV in Australia. By defining the environmental conditions associated with the prevalence of RCV-A1, it also contributes towards understanding the distribution of similar viruses in New Zealand and Europe.

Therapeutic effect of an injectable sustained-release sinomenine hydrochloride and sodium hyaluronate compound in a rabbit model of osteoarthritis.

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Liu, Wen-Guang; Ling, Pei-Xue; Lin, Xiu-Kun; Chen, Jian-Ying; Wang, Shao-Jin; Li, Peng; Wu, Xiao-Juan; Zhao, Dong-Mei; Liu, Sheng-Hou

2012-07-01

While intra-articular injection of sinomenine hydrochloride has a therapeutic effect on osteoarthritis, it has a short half-life, and is thermolabile and photolabile. The aim of this research was to evaluate the sustained-release of sinomenine hydrochloride from an injectable sinomenine hydrochloride and sodium hyaluronate compound (CSSSI) and its therapeutic effect in a rabbit model of osteoarthritis following intra-articular injection. An injectable compound consisting of 1% sodium hyaluronate and 2.5% sinomenine hydrochloride was prepared and kept as the experiment group, and 2.5% sinomenine hydrochloride was prepared and kept as the control group. The cumulative mass release was measured at different time points in each group in vitro. Sixty-five male Zelanian rabbits were randomly divided into five groups: 15 (30 knees) each for the control, sodium hyaluronate, sinomenine hydrochloride, and CSSSI groups respectively, and five (10 knees) for the modeling group. Papain was injected into both knees of each rabbit for model establishment. Subsequently, 0.2 ml of the corresponding drugs was injected into the articular cavities of the remaining experiment groups, while the control group was treated with 0.2 ml normal saline. All groups were treated once a week for 4 weeks. Seven days after the last treatment, knees were anatomized to perform pathological observations and Mankin's evaluation of the synovium. Four groups were compared using the SPSS 13.0 software package. In the in vitro sustained-release experiments, 90% of the drug was released in the experiment group 360 minutes following the injection. Comparison of the Mankin's evaluations of the four groups illustrated statistical discrepancies (P sodium hyaluronate/sinomenine hydrochloride groups, statistical significance was uniformly obtained. Moreover, sodium hyaluronate and sinomenine hydrochloride treatments showed significant improvement over the modeling control (P sodium hyaluronate vs. sinomenine

[Effects of herb cake-separated moxibustion on spleen in immunosuppressive rabbits:a morphology study].

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Tian, Yuefeng; Wu, Aihua; Wang, Jun; Shan, Zengtian

2016-10-12

To observe the influence of different methods of moxibustion on spleen morphology in cyclophosphamide-induced immunosuppressive rabbits. A total of 50 rabbits were randomly assigned into a blank group, a model group, a herbal cake-separated moxibustion group, a moxibustion group and a sham cake-separated moxibustion group, 10 rabbits in each group. Except the blank group, the rabbits in each group were treated with intraperitoneal injection of cyclophosphamide (60 mg/kg), once a day, for 7 consecutive days to establish immunosuppressive model. After the model establishment, the rabbits in the herbal cake-separated moxibustion group were treated with herbal cake-separated moxibustion at "Shenque" (CV 8), "Guanyuan" (CV 4), "Zusanli" (ST 36), "Pishu" (BL 20) and "Shenshu" (BL 23); the moxa cone was placed on the herbal cake which was made of Liuwei Dihuang decoction, three cones for each acupoint. The rabbits in the moxibustion group were treated with moxa stick moxibustion which contained equal moxa of three moxa cones. The rabbits in the sham cake-separated moxibustion group were treated with cake which was made of flour. The acupoint selection in the above three groups was identical, and the intervention was given once every other day for totally 10 times. The rabbits in the blank group and model group were immobilized for identical time without any intervention. After treatment, the rabbits were sacrificed to collect the spleen. With routine HE staining, the morphology changes of spleen were observed under microscope. In addition, the white pulp, splenic corpuscle and the counts of lymphatic cells of lymphatic sheath around the arteries were observed. Compared with the blank group, the average size of white pulp and the radius of splenic corpuscle were reduced (both P 0.05). Compared with the model group, the averagesize of white pulp and the radius of splenic corpuscle were significantly increased in the herbal cake-separated moxibustion group and moxibustion

Fate of bone marrow mesenchymal stromal cells following autologous transplantation in a rabbit model of osteonecrosis.

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Sugaya, Hisashi; Mishima, Hajime; Gao, Ran; Kaul, Sunil C; Wadhwa, Renu; Aoto, Katsuya; Li, Meihua; Yoshioka, Tomokazu; Ogawa, Takeshi; Ochiai, Naoyuki; Yamazaki, Masashi

2016-02-01

Internalizing quantum dots (i-QDs) are a useful tool for tracking cells in vivo in models of tissue regeneration. We previously synthesized i-QDs by conjugating QDs with a unique internalizing antibody against a heat shock protein 70 family stress chaperone. In the present study, i-QDs were used to label rabbit mesenchymal stromal cells (MSCs) that were then transplanted into rabbits to assess differentiation potential in an osteonecrosis model. The i-QDs were taken up by bone marrow-derived MSCs collected from the iliac of 12-week-old Japanese white rabbits that were positive for cluster of differentiation (CD)81 and negative for CD34 and human leukocyte antigen DR. The average rate of i-QD internalization was 93.3%. At 4, 8, 12, and 24 weeks after transplantation, tissue repair was evaluated histologically and by epifluorescence and electron microscopy. The i-QDs were detected at the margins of the drill holes and in the necrotized bone trabecular. There was significant colocalization of the i-QD signal in transplanted cells and markers of osteoblast and mineralization at 4, 8, and 12 weeks post-transplantation, while i-QDs were detected in areas of mineralization at 12 and 24 weeks post-transplantation. Moreover, i-QDs were observed in osteoblasts in regenerated tissue by electron microscopy, demonstrating that the tissue was derived from transplanted cells. These results indicate that transplanted MSCs can differentiate into osteoblasts and induce tissue repair in an osteonecrosis model and can be tracked over the long term by i-QD labeling. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Comparison of biological behavior of 99Tcm-ciprofloxacin (Infecton) and 99Tcm-HIgG in rabbit models of inflammation

International Nuclear Information System (INIS)

He Wei; Chen Shaoliang; Mao Jinlei; Jiang Maosong

2008-01-01

Objective: 99 Tc m -ciprofloxacin(Infecton) and 99 Tc m -HIgG are both radiopharmaceuticals for inflammation and infectious disease imaging. It was reported that 99 Tc m -ciprofloxacin (Infecton)was able to distinguish inflammation from infection, while 99 Tc m -HIgG was a nonspecific agent. The study was designed to compare the in vivo characteristics between 99 Tc m -ciprofloxacin(Infecton) and 99 Tc m -HIgC in rabbit model of inflammation. Methods: Eight rabbits were grouped as inflammation model (the first group), infection mod- el (the second group), concomitant inflammation and infection model (the third group), and control (the fourth group) groups. A total of 185 MBq (0.5 ml) 99 Tc m -ciprofloxacin (Infecton) was administered intravenously to each rabbit, a serious dynamic images were acquired till 24 h post-injection. Repeated examination with 99 Tc m -HIgG was carried out 2 d later. Results: 99 Tc m -ciprofloxacin (Infecton) scan was negative in the inflammation models and controls, and was positive in the infection models. In the third group 99 Tc m - ciprofloxacin (Infecton) showed infection focus in the left thigh but negative uptake at inflammation focus in the right thigh. 99 Tc m -HIgG scan were positive in all models. The optimal image time for 99 Tc m -ciproftoxacin (Infecton) was 3 h after administration, but positive image could still be observed 24 h later. Conclusion 99 Tc m -ciprofloxacin (Infecton) appears to specifically accumulate in the infective lesion. (authors)

RabbitMQ essentials

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Dossot, David

2014-01-01

This book is a quick and concise introduction to RabbitMQ. Follow the unique case study of Clever Coney Media as they progressively discover how to fully utilize RabbitMQ, containing clever examples and detailed explanations.Whether you are someone who develops enterprise messaging products professionally or a hobbyist who is already familiar with open source Message Queuing software and you are looking for a new challenge, then this is the book for you. Although you should be familiar with Java, Ruby, and Python to get the most out of the examples, RabbitMQ Essentials will give you the push y

Efficacy of silk fibroin–nano silver against Staphylococcus aureus biofilms in a rabbit model of sinusitis

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Jia M

2017-04-01

Full Text Available Minghui Jia,1,2 Zhongchun Chen,2 Yongwei Guo,2 Xin Chen,3 Xia Zhao2 1Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 2Department of Otolaryngology-Head and Neck Surgery, Huashan Hospital, Fudan University, 3State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Laboratory of Advanced Materials, Fudan University, Shanghai, China Background: Staphylococcus aureus biofilms contribute significantly to the recalcitrant nature of chronic rhinosinusitis. In previous studies, it has been shown that silk fibroin–nano silver solution can eliminate S. aureus biofilms in vitro, which suggests a potential role of this novel agent in the treatment of biofilm-associated diseases, such as sinusitis.Objective: The aim of this study was to investigate the efficacy of silk fibroin–nano silver solution as a topical anti-biofilm agent in a rabbit model of sinusitis.Methods: Biofilm-associated sinusitis models were established in 24 New Zealand White rabbits by gelatin sponge placement and S. aureus inoculation through a hole drilled into the anterolateral wall of the right maxillary sinus. After 4 weeks, indwelling catheters were placed into the maxillary sinus. Different concentrations of silk fibroin–nano silver solution or normal saline were irrigated slowly into the maxillary sinus via the indwelling catheters. After 7 days of irrigation, the rabbits were sacrificed. The sinus mucosa was harvested and examined for biofilm biomass as well as morphological integrity of the epithelium by scanning electron microscopy.Results: Silk fibroin–nano silver solution was found to be most effective in reducing the biomass of the S. aureus biofilms at a concentration of 384 mg/L, followed by the concentration of 153.6 mg/L, when compared with saline. After treatment with 384 mg/L silk fibroin–nano silver solution, the biofilms were completely

A new flow-diverter(the FloWise): In vivo evaluation in an elastase-induced rabbit aneurysm model

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Kim, Byung Moon; Kim, Dong Joon; Kim, Dong Ik [Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

2016-02-15

We aimed to evaluate the efficacy and safety of a newly developed, partially retrievable flow-diverter (the FloWise) in an elastase-induced rabbit aneurysm model. We developed a partially retrievable flow diverter composed of 48 strands of Nitinol and platinum wire. The FloWise is compatible with any microcatheter of 0.027-inch inner diameter, and is retrievable up to 70% deployment. The efficacy and safety of the FloWise were evaluated in the elastase-induced rabbit aneurysm model. The rate of technical success (full coverage of aneurysm neck) and assessment of aneurysm occlusion and stent patency was conducted by angiograms and histologic examinations at the 1-month, 3-month, and 6-month follow-up. The patency of small arterial branches (intercostal or lumbar arteries) covered by the FloWise were also assessed in the 5 subjects. We attempted FloWise insertion in a total of 32 aneurysm models. FloWise placement was successful in 31 subjects (96.9%). Two stents (6.2%) were occluded at the 3-month follow-up, but there was no evidence of in-stent stenosis in other subjects. All stented aneurysms showed progressive occlusion: grade I (complete aneurysm occlusion) in 44.4% and grade II (aneurysm occlusion > 90%) in 55.6% at 1 month; grade I in 90% and II in 10% at 3 months; and grade I in 90% and II in 10% at 6 months. All small arterial branches covered by the FloWise remained patent. A newly developed, partially retrievable flow-diverter seems to be a safe and effective tool of aneurysm occlusion, as evaluated in the rabbit aneurysm model.

Cryotherapy increases features of plaque stability in atherosclerotic rabbits.

Science.gov (United States)

Verheye, Stefan; Roth, Lynn; De Meyer, Inge; Van Hove, Cor E; Nahon, Daniel; Santoianni, Domenic; Yianni, John; Martinet, Wim; Buchbinder, Maurice; De Meyer, Guido R Y

2016-08-20

In the last 10 years, cryotherapy has been investigated as a new technology to treat vascular disease. The efficiency of cryotherapy in stabilising atherosclerotic plaques has never been described. The purpose of the present study was to evaluate the effect of catheter-based cryotherapy on atherosclerotic plaque composition in a rabbit model of atherosclerosis. Twenty-four New Zealand white rabbits were fed a 0.3% cholesterol-supplemented diet for 24 weeks. At two predefined sites of the atherosclerotic thoracic aorta, catheter-based cryotherapy, applying either single-dose, double-dose cryotherapy or control inflation, was performed after randomisation. Rabbits were continued on a cholesterol-supplemented diet for one day (acute) or four weeks (chronic). One day after cryotherapy, apoptotic cell death of smooth muscle cells (SMCs) and endothelial cells (ECs) was observed, whereas macrophages were unaffected. Four weeks later, the amount of SMCs was restored, the EC layer was regenerated, and a subendothelial macrophage-free layer was formed, indicative of a more stable plaque. In addition, both the thickness and the type I collagen content of the fibrous cap were increased. The present study demonstrated that cryotherapy is feasible and appears to stabilise atherosclerotic plaques in a rabbit model.

A comparison of scintigraphy with tumor-seeking radiopharmaceuticals to detect an experimental bone tumors in the rabbits

International Nuclear Information System (INIS)

Otsuka, Nobuaki; Sone, Teruki; Fukunaga, Masao

2003-01-01

A comparative study on the accumulation of 99m Tc-phosphorous compound, 99m Tc-hexakis-2-methoxy isobutyl-isonitrile (MIBI), and 99m Tc-tetrofosmin (TF) in the experimental bone tumors using the VX-2 cell was performed. In the group of the femoral metastatic bone tumor, 99m Tc-MIBI showed no accumulation in the femur at 12 days after the transplantation despite the presence of a bone marrow tumor. In the group of the iliac metastatic bone tumor, a bone scintigraphy showed decreased accumulation in the ileum at 16 days, but hot lesions were observed in same sites at 18 days after the transplantation on 99m Tc-MIBI and 99m Tc-TF scintigrams. The tumor to soft tissue accumulation ratio was higher for 99m Tc-MIBI (3.03±1.03) than for 99m Tc-TF (2.55±0.80) (P 99m Tc-MIBI is less satisfactory for the early diagnosis of tumors than bone scintigraphy, and a combined study with both 99m Tc-phosphorous compounds and 99m Tc-MIBI is useful for the evaluation and diagnosis of lesions. (author)

Roles of the WHHL Rabbit in Translational Research on Hypercholesterolemia and Cardiovascular Diseases

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Tsutomu Kobayashi

2011-01-01

Full Text Available Conquering cardiovascular diseases is one of the most important problems in human health. To overcome cardiovascular diseases, animal models have played important roles. Although the prevalence of genetically modified animals, particularly mice and rats, has contributed greatly to biomedical research, not all human diseases can be investigated in this way. In the study of cardiovascular diseases, mice and rats are inappropriate because of marked differences in lipoprotein metabolism, pathophysiological findings of atherosclerosis, and cardiac function. On the other hand, since lipoprotein metabolism and atherosclerotic lesions in rabbits closely resemble those in humans, several useful animal models for these diseases have been developed in rabbits. One of the most famous of these is the Watanabe heritable hyperlipidemic (WHHL rabbit, which develops hypercholesterolemia and atherosclerosis spontaneously due to genetic and functional deficiencies of the low-density lipoprotein (LDL receptor. The WHHL rabbit has been improved to develop myocardial infarction, and the new strain was designated the myocardial infarction-prone WHHL (WHHLMI rabbit. This review summarizes the importance of selecting animal species for translational research in biomedical science, the development of WHHL and WHHLMI rabbits, their application to the development of hypocholesterolemic and/or antiatherosclerotic drugs, and future prospects regarding WHHL and WHHLMI rabbits.

Assessment of contrast enhanced respiration managed cone-beam CT for image guided radiotherapy of intrahepatic tumors

International Nuclear Information System (INIS)

Jensen, Nikolaj K. G.; Stewart, Errol; Lock, Michael; Fisher, Barbara; Kozak, Roman; Chen, Jeff; Lee, Ting-Yim; Wong, Eugene

2014-01-01

Purpose: Contrast enhancement and respiration management are widely used during image acquisition for radiotherapy treatment planning of liver tumors along with respiration management at the treatment unit. However, neither respiration management nor intravenous contrast is commonly used during cone-beam CT (CBCT) image acquisition for alignment prior to radiotherapy. In this study, the authors investigate the potential gains of injecting an iodinated contrast agent in combination with respiration management during CBCT acquisition for liver tumor radiotherapy. Methods: Five rabbits with implanted liver tumors were subjected to CBCT with and without motion management and contrast injection. The acquired CBCT images were registered to the planning CT to determine alignment accuracy and dosimetric impact. The authors developed a simulation tool for simulating contrast-enhanced CBCT images from dynamic contrast enhanced CT imaging (DCE-CT) to determine optimal contrast injection protocols. The tool was validated against contrast-enhanced CBCT of the rabbit subjects and was used for five human patients diagnosed with hepatocellular carcinoma. Results: In the rabbit experiment, when neither motion management nor contrast was used, tumor centroid misalignment between planning image and CBCT was 9.2 mm. This was reduced to 2.8 mm when both techniques were employed. Tumors were not visualized in clinical CBCT images of human subjects. Simulated contrast-enhanced CBCT was found to improve tumor contrast in all subjects. Different patients were found to require different contrast injections to maximize tumor contrast. Conclusions: Based on the authors’ animal study, respiration managed contrast enhanced CBCT improves IGRT significantly. Contrast enhanced CBCT benefits from patient specific tracer kinetics determined from DCE-CT

Assessment of contrast enhanced respiration managed cone-beam CT for image guided radiotherapy of intrahepatic tumors

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Jensen, Nikolaj K. G., E-mail: nkyj@regionsjaelland.dk [Physics and Engineering, London Regional Cancer Program, London, Ontario N6A3K7 (Canada); Stewart, Errol [Radiology, St. Joseph' s Health Care, London, Ontario N6A 4V2 (Canada); Imaging Research Lab, Robarts Research Institute, London, Ontario N6A 5B7 (Canada); Imaging Program, Lawson Health Research Institute, London, Ontario N6C 2R5 (Canada); Lock, Michael; Fisher, Barbara [Radiation Oncology, London Regional Cancer Program, London, Ontario N6A3K7 (Canada); Department of Oncology, University of Western Ontario, London, Ontario N6A 4L6 (Canada); Kozak, Roman [Radiology, St. Joseph' s Health Care, London, Ontario N6A 4V2 (Canada); Chen, Jeff [Physics and Engineering, London Regional Cancer Program, London, Ontario N6A3K7 (Canada); Department of Oncology, University of Western Ontario, London, Ontario N6A 4L6 (Canada); Department of Medical Biophysics, University of Western Ontario, London, Ontario N6A 5C1 (Canada); Lee, Ting-Yim [Radiology, St. Joseph' s Health Care, London, Ontario N6A 4V2 (Canada); Imaging Research Lab, Robarts Research Institute, London, Ontario N6A 5B7 (Canada); Imaging Program, Lawson Health Research Institute, London, Ontario N6C 2R5 (Canada); Department of Oncology, University of Western Ontario, London, Ontario N6A 4L6 (Canada); Department of Medical Biophysics, University of Western Ontario, London, Ontario N6A 5C1 (Canada); Wong, Eugene [Physics and Engineering, London Regional Cancer Program, London, Ontario N6A3K7 (Canada); Department of Oncology, University of Western Ontario, London, Ontario N6A 4L6 (Canada); Department of Medical Biophysics, University of Western Ontario, London, Ontario N6A 5C1 (Canada); Department of Physics and Astronomy, University of Western Ontario, London, Ontario N6A 3K7 (Canada)

2014-05-15

Purpose: Contrast enhancement and respiration management are widely used during image acquisition for radiotherapy treatment planning of liver tumors along with respiration management at the treatment unit. However, neither respiration management nor intravenous contrast is commonly used during cone-beam CT (CBCT) image acquisition for alignment prior to radiotherapy. In this study, the authors investigate the potential gains of injecting an iodinated contrast agent in combination with respiration management during CBCT acquisition for liver tumor radiotherapy. Methods: Five rabbits with implanted liver tumors were subjected to CBCT with and without motion management and contrast injection. The acquired CBCT images were registered to the planning CT to determine alignment accuracy and dosimetric impact. The authors developed a simulation tool for simulating contrast-enhanced CBCT images from dynamic contrast enhanced CT imaging (DCE-CT) to determine optimal contrast injection protocols. The tool was validated against contrast-enhanced CBCT of the rabbit subjects and was used for five human patients diagnosed with hepatocellular carcinoma. Results: In the rabbit experiment, when neither motion management nor contrast was used, tumor centroid misalignment between planning image and CBCT was 9.2 mm. This was reduced to 2.8 mm when both techniques were employed. Tumors were not visualized in clinical CBCT images of human subjects. Simulated contrast-enhanced CBCT was found to improve tumor contrast in all subjects. Different patients were found to require different contrast injections to maximize tumor contrast. Conclusions: Based on the authors’ animal study, respiration managed contrast enhanced CBCT improves IGRT significantly. Contrast enhanced CBCT benefits from patient specific tracer kinetics determined from DCE-CT.

Serological Survey for RHD Antibodies in Rabbits from Two Types of Rabbit Breeding Farms.

Science.gov (United States)

Fitzner, A; Niedbalski, W

2016-09-01

Seroprevalence studies of RHDV antibodies in domestic rabbits were conducted between 2008-2014. A total of 12,169 sera from the provinces of central, southern and south-east Poland, including 7,570 samples collected from mixed-breed rabbits reared in smallholder farms and nearly 4,600 sera taken mainly from unvaccinated rabbits kept in industrial farms, were examined using ELISA tests. Additionally, cross-reactivity of selected tested and control archival sera using both classic RHDV and RHDVa antigens was determined by HI assay. The overall seroprevalence was 13.3%. In rabbits with unkown history of immunisation or RHD infection which came from small farms, RHDV antibodies were detected in 6.1% ranging between 1.0% to 17.2% of animals. In rabbits of the same group, but with a declared vaccination status, or confirmed exposure to an infectious virus, or coming from exposed females, the seroprevalence ranged from 83% to 100%. Among unvaccinated meat rabbits aged 71 to 90 days from industrial farms, low (1.85%, 4.17%, 11%), medium (34%, 54%) or high rates (98.7%) of seropositivity were detected. The seroconversion recorded in adult vaccinated females from industrial farms was 70% and 95%. Generally, the antibody levels examined by ELISAs and HI were comparable. However, a number of sera from the rabbits from small farms, as well as archival sera, showed clear differences. Several-fold differences in antibody titers, evidenced mainly in the postoutbreak sera, indictaed the contact of animals with RHDVa antigen. The overall results of the survey revealed a great proportion of seronegative rabbits potentially highly susceptible to RHD infection. In combination with the emergence of a novel pathogenic RHD virus type (RHDV2), it poses a severe risk of a next wave of fatal disease cases spreading in the native population of domestic rabbits, especially in farms with a traditional system of husbandry.

Gene Directed Enzyme Prodrug Therapy Using Rabbit Cytochrome P450 4B1 in Murine Colon Adenocarcinoma

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Kim, Sung Joo; Kang, Joo Hyun; Lee, Tae Sup; Kim, Kyeong Min; Woo, Kwang Sun; Chung, Wee Sup; Cheon, Gi Jeong; Choi, Chang Woon; Lim, Sang Moo [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

2007-07-01

The conventional cancer therapy is chemotherapy, surgical resection and/or radiotherapy. Chemotherapy using cytotoxic drug has some problems with lack of tumor selectivity resulting in toxicity to normal tissues. To enhance the tumor selectivity of cytotoxic drug, the application of suicidal gene therapy technology was designed. Suicidal gene therapy is based on the expression in tumor cells of a gene encoding an enzyme that converts a non-toxic prodrug into a cytotoxic product. Representative suicidal genes are Herpes simplex virus type 1 thymidine kinase (HSV1- tk) and cytosine deaminase (cd). Recently, a new prodrug-converting enzyme based on rabbit cytochrome P450 4B1 gene (cyp4B1) has been reported for therapy of experimental brain tumor. This enzyme activates the prodrugs such as 4-ipomeanol (4-IM) and 2- aminoanthracene (2-AA) to highly reactive furane epoxide and unsaturated dialdehyde intermediate, respectively. DNA alkylation seems to be the main mechanism of cytotoxicity of these activated drugs. In this study, we isolated cyp4B1 cDNA from rabbit lung, transduced cyp4B1 expression vector into murine colon cancer cell, and then analyzed the cytotoxic properties of cyp4b1-activated 2-AA in cyp4B1 transduced cells to verify the cyp4B1 enzyme system for gene directed enzyme prodrug therapy.

Gene Directed Enzyme Prodrug Therapy Using Rabbit Cytochrome P450 4B1 in Murine Colon Adenocarcinoma

International Nuclear Information System (INIS)

Kim, Sung Joo; Kang, Joo Hyun; Lee, Tae Sup; Kim, Kyeong Min; Woo, Kwang Sun; Chung, Wee Sup; Cheon, Gi Jeong; Choi, Chang Woon; Lim, Sang Moo

2007-01-01

The conventional cancer therapy is chemotherapy, surgical resection and/or radiotherapy. Chemotherapy using cytotoxic drug has some problems with lack of tumor selectivity resulting in toxicity to normal tissues. To enhance the tumor selectivity of cytotoxic drug, the application of suicidal gene therapy technology was designed. Suicidal gene therapy is based on the expression in tumor cells of a gene encoding an enzyme that converts a non-toxic prodrug into a cytotoxic product. Representative suicidal genes are Herpes simplex virus type 1 thymidine kinase (HSV1- tk) and cytosine deaminase (cd). Recently, a new prodrug-converting enzyme based on rabbit cytochrome P450 4B1 gene (cyp4B1) has been reported for therapy of experimental brain tumor. This enzyme activates the prodrugs such as 4-ipomeanol (4-IM) and 2- aminoanthracene (2-AA) to highly reactive furane epoxide and unsaturated dialdehyde intermediate, respectively. DNA alkylation seems to be the main mechanism of cytotoxicity of these activated drugs. In this study, we isolated cyp4B1 cDNA from rabbit lung, transduced cyp4B1 expression vector into murine colon cancer cell, and then analyzed the cytotoxic properties of cyp4b1-activated 2-AA in cyp4B1 transduced cells to verify the cyp4B1 enzyme system for gene directed enzyme prodrug therapy

Radioiodinated VEGF to image tumor angiogenesis in a LS180 tumor xenograft model

International Nuclear Information System (INIS)

Yoshimoto, Mitsuyoshi; Kinuya, Seigo; Kawashima, Atsuhiro; Nishii, Ryuichi; Yokoyama, Kunihiko; Kawai, Keiichi

2006-01-01

Introduction: Angiogenesis is essential for tumor growth or metastasis. A method involving noninvasive detection of angiogenic activity in vivo would provide diagnostic information regarding antiangiogenic therapy targeting vascular endothelial cells as well as important insight into the role of vascular endothelial growth factor (VEGF) and its receptor (flt-1 and KDR) system in tumor biology. We evaluated radioiodinated VEGF 121 , which displays high binding affinity for KDR, and VEGF 165 , which possesses high binding affinity for flt-1 and low affinity for KDR, as angiogenesis imaging agents using the LS180 tumor xenograft model. Methods: VEGF 121 and VEGF 165 were labeled with 125 I by the chloramine-T method. Biodistribution was observed in an LS180 human colon cancer xenograft model. Additionally, autoradiographic imaging and immunohistochemical staining of tumors were performed with 125 I-VEGF 121 . Results: 125 I-VEGF 121 and 125 I-VEGF 165 exhibited strong, continuous uptake by tumors and the uterus, an organ characterized by angiogenesis. 125 I-VEGF 121 uptake in tumors was twofold higher than that of 125 I-VEGF 165 (9.12±98 and 4.79±1.08 %ID/g at 2 h, respectively). 125 I-VEGF 121 displayed higher tumor to nontumor (T/N) ratios in most normal organs in comparison with 125 I-VEGF 165 . 125 I-VEGF 121 accumulation in tumors decreased with increasing tumor volume. Autoradiographic and immunohistochemical analyses confirmed that the difference in 125 I-VEGF 121 tumor accumulation correlated with degree of tumor vascularity. Conclusion: Radioiodinated VEGF 121 is a promising tracer for noninvasive delineation of angiogenesis in vivo

A Rabbit Model for Testing Helper-Dependent Adenovirus-Mediated Gene Therapy for Vein Graft Atherosclerosis.

Science.gov (United States)

Bi, Lianxiang; Wacker, Bradley K; Bueren, Emma; Ham, Ervin; Dronadula, Nagadhara; Dichek, David A

2017-12-15

Coronary artery bypass vein grafts are a mainstay of therapy for human atherosclerosis. Unfortunately, the long-term patency of vein grafts is limited by accelerated atherosclerosis. Gene therapy, directed at the vein graft wall, is a promising approach for preventing vein graft atherosclerosis. Because helper-dependent adenovirus (HDAd) efficiently transduces grafted veins and confers long-term transgene expression, HDAd is an excellent candidate for delivery of vein graft-targeted gene therapy. We developed a model of vein graft atherosclerosis in fat-fed rabbits and demonstrated long-term (≥20 weeks) persistence of HDAd genomes after graft transduction. This model enables quantitation of vein graft hemodynamics, wall structure, lipid accumulation, cellularity, vector persistence, and inflammatory markers on a single graft. Time-course experiments identified 12 weeks after transduction as an optimal time to measure efficacy of gene therapy on the critical variables of lipid and macrophage accumulation. We also used chow-fed rabbits to test whether HDAd infusion in vein grafts promotes intimal growth and inflammation. HDAd did not increase intimal growth, but had moderate-yet significant-pro-inflammatory effects. The vein graft atherosclerosis model will be useful for testing HDAd-mediated gene therapy; however, pro-inflammatory effects of HdAd remain a concern in developing HDAd as a therapy for vein graft disease.

Simple Additive Weighting to Diagnose Rabbit Disease

Science.gov (United States)

Ramadiani; Marissa, Dyna; Jundillah, Muhammad Labib; Azainil; Hatta, Heliza Rahmania

2018-02-01

Rabbit is one of the many pets maintained by the general public in Indonesia. Like other pet, rabbits are also susceptible to various diseases. Society in general does not understand correctly the type of rabbit disease and the way of treatment. To help care for sick rabbits it is necessary a decision support system recommendation diagnosis of rabbit disease. The purpose of this research is to make the application of rabbit disease diagnosis system so that can help user in taking care of rabbit. This application diagnoses the disease by tracing the symptoms and calculating the recommendation of the disease using Simple Additive Weighting method. This research produces a web-based decision support system that is used to help rabbit breeders and the general public.

Effect of Temperature-Sensitive Poloxamer Solution/Gel Material on Pericardial Adhesion Prevention: Supine Rabbit Model Study Mimicking Cardiac Surgery.

Directory of Open Access Journals (Sweden)

Hyun Kang

Full Text Available We investigated the mobility of a temperature-sensitive poloxamer/Alginate/CaCl2 mixture (PACM in relation to gravity and cardiac motion and the efficacy of PACM on the prevention of pericardial adhesion in a supine rabbit model.A total of 50 rabbits were randomly divided into two groups according to materials applied after epicardial abrasion: PACM and dye mixture (group PD; n = 25 and saline as the control group (group CO; n = 25. In group PD, rabbits were maintained in a supine position with appropriate sedation, and location of mixture of PACM and dye was assessed by CT scan at the immediate postoperative period and 12 hours after surgery. The grade of adhesions was evaluated macroscopically and microscopically two weeks after surgery.In group PD, enhancement was localized in the anterior pericardial space, where PACM and dye mixture was applied, on immediate post-surgical CT scans. However, the volume of the enhancement was significantly decreased at the anterior pericardial space 12 hours later (P < .001. Two weeks after surgery, group PD had significantly lower macroscopic adhesion score (P = .002 and fibrosis score (P = .018 than did group CO. Inflammation score and expression of anti-macrophage antibody in group PD were lower than those in group CO, although the differences were not significant.In a supine rabbit model study, the anti-adhesion effect was maintained at the area of PACM application, although PACM shifted with gravity and heart motion. For more potent pericardial adhesion prevention, further research and development on the maintenance of anti-adhesion material position are required.

Pseudogenization of the MCP-2/CCL8 chemokine gene in European rabbit (genus Oryctolagus, but not in species of Cottontail rabbit (Sylvilagus and Hare (Lepus

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van der Loo Wessel

2012-08-01

Full Text Available Abstract Background Recent studies in human have highlighted the importance of the monocyte chemotactic proteins (MCP in leukocyte trafficking and their effects in inflammatory processes, tumor progression, and HIV-1 infection. In European rabbit (Oryctolagus cuniculus one of the prime MCP targets, the chemokine receptor CCR5 underwent a unique structural alteration. Until now, no homologue of MCP-2/CCL8a, MCP-3/CCL7 or MCP-4/CCL13 genes have been reported for this species. This is interesting, because at least the first two genes are expressed in most, if not all, mammals studied, and appear to be implicated in a variety of important chemokine ligand-receptor interactions. By assessing the Rabbit Whole Genome Sequence (WGS data we have searched for orthologs of the mammalian genes of the MCP-Eotaxin cluster. Results We have localized the orthologs of these chemokine genes in the genome of European rabbit and compared them to those of leporid genera which do (i.e. Oryctolagus and Bunolagus or do not share the CCR5 alteration with European rabbit (i.e. Lepus and Sylvilagus. Of the Rabbit orthologs of the CCL8, CCL7, and CCL13 genes only the last two were potentially functional, although showing some structural anomalies at the protein level. The ortholog of MCP-2/CCL8 appeared to be pseudogenized by deleterious nucleotide substitutions affecting exon1 and exon2. By analyzing both genomic and cDNA products, these studies were extended to wild specimens of four genera of the Leporidae family: Oryctolagus, Bunolagus, Lepus, and Sylvilagus. It appeared that the anomalies of the MCP-3/CCL7 and MCP-4/CCL13 proteins are shared among the different species of leporids. In contrast, whereas MCP-2/CCL8 was pseudogenized in every studied specimen of the Oryctolagus - Bunolagus lineage, this gene was intact in species of the Lepus - Sylvilagus lineage, and was, at least in Lepus, correctly transcribed. Conclusion The biological function of a gene was often

The effect of TACE with endostatin on hemodynamics in hepatic implantation tumor using Doppler ultrasonography

International Nuclear Information System (INIS)

Zhou Guangli; Wu Yuanyuan; Wang Bin; Liu Yan; Zheng Chuanli; Sang Li; Liu Feng

2009-01-01

Objective: To investigate the hemodynamic changes in the rabbit liver and VX2 hepatic implantation tumor after treatment by transcatheter arterial chemoembolization (TACE)/endostatin using Doppler ultrasonography. Methods: Twenty rabbits with VX2 hepatic tumor were randomly distributed into the control group (n=10) and the anti- angiogenesis group (n=10). The rabbits were administered with endostatin and adriamycin-lipiodol in the anti-angiogenesis group and with 37℃ saline in the control group via hepatic artery. The hemodynamic changes of the tumors, hepatic artery, and portal vein were recorded with Doppler ultrasonography 1 week after the treatment. The results before and after the treatment were compared. Results: In the control group, the maximal hepatic artery blood flow velocity was significantly higher than that before the treatment (P<0.05). However, the resistance index and the portal vein blood flow velocities had no significantly change compared with those before the treatment (P>0.05). In the anti-angiogenesis group, the hepatic artery blood flow velocity was significantly lower than that before the treatment (P<0.05), and the resistance index was increased (P<0.05). However, the portal vein blood flow velocity had no significantly change (P>0.05). The blood flow signal in all tumors was rich before embolization. After TACE, the blood flow signal was significantly decreased, even partly disappeared in the anti-angiogenesis group. Conclusion: TACE with endostatin can effectively block the blood supplement of VX2 hepatic implantation tumor. Doppler ultrasonography can detected the blood flow changes and can be used in evaluating the therapeutic effect in hepatic implantation tumor. (authors)

Autologous leukocyte-reduced platelet-rich plasma therapy for Achilles tendinopathy induced by collagenase in a rabbit model.

Science.gov (United States)

González, Juan C; López, Catalina; Álvarez, María E; Pérez, Jorge E; Carmona, Jorge U

2016-01-19

Leukocyte-reduced platelet-rich plasma (LR-PRP) is a therapy for tendinopathy of the Achilles tendon (TAT); however, there is scarce information regarding LR-PRP effects in rabbit models of TAT. We compared, at 4 and 12 weeks (w), the LR-PRP and placebo (PBS) effects on ultrasonography, histology and relative gene expression of collagen types I (COL1A1) and III (COL3A1) and vascular endothelial growth factor (VEGF) in 24 rabbits with TAT induced by collagenase. The rabbits (treated with both treatments) were euthanatised after either 4 or 12 w. A healthy group (HG (n = 6)) was included. At 4 and 12 w, the LR-PRP group had a no statistically different histology score to the HG. At w 4, the COL1A1 expression was significantly higher in the LR-PRP group when compared to HG, and the expression of COL3A1 from both LR-PRP and PBS-treated tendons was significantly higher when compared to the HG. At w 12, the expression of COL3A1 remained significantly higher in the PBS group in comparison to the LR-PRP group and the HG. At w 4, the LR-PRP group presented a significantly higher expression of VEGF when compared to the PBS group and the HG. In conclusion, LR-PRP treatment showed regenerative properties in rabbits with TAT.

Therapeutic Implications from Sensitivity Analysis of Tumor Angiogenesis Models

Science.gov (United States)

Poleszczuk, Jan; Hahnfeldt, Philip; Enderling, Heiko

2015-01-01

Anti-angiogenic cancer treatments induce tumor starvation and regression by targeting the tumor vasculature that delivers oxygen and nutrients. Mathematical models prove valuable tools to study the proof-of-concept, efficacy and underlying mechanisms of such treatment approaches. The effects of parameter value uncertainties for two models of tumor development under angiogenic signaling and anti-angiogenic treatment are studied. Data fitting is performed to compare predictions of both models and to obtain nominal parameter values for sensitivity analysis. Sensitivity analysis reveals that the success of different cancer treatments depends on tumor size and tumor intrinsic parameters. In particular, we show that tumors with ample vascular support can be successfully targeted with conventional cytotoxic treatments. On the other hand, tumors with curtailed vascular support are not limited by their growth rate and therefore interruption of neovascularization emerges as the most promising treatment target. PMID:25785600

Optic nerve tolerance to single and fractionated radiation simulating radiosurgery: a rabbit model using visual evoked potentials, fundoscopy and histology

International Nuclear Information System (INIS)

Bastin, Kenneth; Mehta, Minesh

1997-01-01

Purpose/Objective: To develop a rabbit model enabling single or fractionated optic nerve irradiation, measure post-irradiation visual evoked potentials (VEP), fundoscopic and histopathologic changes, and relate different radiation dosing fractions to these measurable physiologic changes. Materials and Methods: Forty male New Zealand white rabbits underwent surgical right orbital prolapse with template-guided optic nerve irradiation using an iridium-192 high dose rate afterloader. Rabbits were randomized into single fraction groups (0 (control), 10, 12.5, 15, 20, and 30 Gy (3 per group); or two fraction groups of 0 (control) 5, 7.5, 10, 15, and 20 Gy (3 per group); or three fractions groups of 10 and 15 Gy (2 per group). Bilateral fundoscopy and pattern-reversal VEPs (0.5 and 1 c/deg, 1 hertz) were performed at 6 and 12 months (mos) following scheduled irradiation. VEP peaks (P1) were measured. Sacrifice and necropsy followed 12 month evaluation, allowing for histological changes. Results: Excluding deaths from anesthesia (2), CNS mite infection (2), sepsis, pyothorax, 'undetermined' and technically non-analyzable VEP recordings, 24 complete rabbit data sets were evaluated. Fundoscopy demonstrated no gross changes at any dose. Histopathology demonstrated generalized optic nerve atrophy without radiation dose correlation. Among single fraction groups, VEP showed a 6 mos post-irradiation P1 prolongation only in the 20 and 30 Gy groups (maximum 67%). At 12 mos lower dose single fraction groups had a prolonged P1 peak. All fractionated groups above 5 Gy x 2 had P1 prolongation times at 6 mos (maximum 46% in the 15 Gy x 3 data set) but by 12 mos these groups had non-measurable, deteriorated VEPs. Correlating VEP P1 latency with the calculated linear quadratic formula (LQM) biologically equivalent dose (BED,α/β=3) for each group demonstrated a general correlation (t-Test P<.001) as shown: Conclusion: Using a rabbit model for selective optic nerve irradiation we conclude

Self-expandable stent loaded with {sup 125}I seeds: Feasibility and safety in a rabbit model

Energy Technology Data Exchange (ETDEWEB)

Guo Jinhe [Department of Radiology, Zhong-Da Hospital, Southeast University, 87 Dingjiaqiao Road, Nanjing 210009 (China); Teng Gaojun [Department of Radiology, Zhong-Da Hospital, Southeast University, 87 Dingjiaqiao Road, Nanjing 210009 (China)]. E-mail: gjteng@vip.sina.com; Zhu Guangyu [Department of Radiology, Zhong-Da Hospital, Southeast University, 87 Dingjiaqiao Road, Nanjing 210009 (China); He Shicheng [Department of Radiology, Zhong-Da Hospital, Southeast University, 87 Dingjiaqiao Road, Nanjing 210009 (China); Deng Gang [Department of Radiology, Zhong-Da Hospital, Southeast University, 87 Dingjiaqiao Road, Nanjing 210009 (China); He Jie [Department of Radiology, Zhong-Da Hospital, Southeast University, 87 Dingjiaqiao Road, Nanjing 210009 (China)

2007-02-15

Objective: To evaluate technical feasibility and acute and subacute radiotolerance of a self-expandable stent loaded with {sup 125}I seeds in the rabbit esophagus. Methods: A self-expandable stent designed for esophageal application was made of 0.16 mm nitinol wire and loaded with {sup 125}I seeds (CIAE-6711). Twenty-seven stents with three different radioactive dosages (n = 9 in each dosage group) were implanted in the esophagus of healthy rabbits, while nine stents alone were used as controls. The stents were perorally deployed into the esophagus under fluoroscopic guidance. Radiological follow-up included plain chest film, CT scan, and barium esophagography which were undertaken in all rabbits of each group at 2, 4, and 8 weeks, respectively, which were correlated to histopathological findings. The stented esophageal segments along with their adjacent tissues were harvested for histopathological examinations. Results: The stent was successfully deployed into the targeted esophageal segment in all rabbits. Neither {sup 125}I seeds dislodged from the stent during the deployment, nor they did during the follow-up period. The greatest (16.2 Gy) absorbed dose was found in the tissue 10 mm from {sup 125}I seeds at 8 weeks. Slight epithelial hyperplasia on the stent surface and submucosal inflammatory process developed at 2 weeks, which reached the peak at 8 weeks after the procedure. Significant thickness of the esophageal muscular layer was found at 8 weeks only in the groups with {sup 125}I seeds. On radiologic follow-up, moderate strictures on both ends of the stents developed at 4 weeks and became severe at 8 weeks after the procedure in all groups. Conclusion: Deployment of a self-expandable stent loaded with {sup 125}I seeds is technically feasible and safe within the first 8 weeks. Acute and subacute radiotolerance of the treated esophagus and its adjacent tissues by {sup 125}I seeds is well preserved in a healthy rabbit model.

Simple Additive Weighting to Diagnose Rabbit Disease

Directory of Open Access Journals (Sweden)

Ramadiani

2018-01-01

Full Text Available Rabbit is one of the many pets maintained by the general public in Indonesia. Like other pet, rabbits are also susceptible to various diseases. Society in general does not understand correctly the type of rabbit disease and the way of treatment. To help care for sick rabbits it is necessary a decision support system recommendation diagnosis of rabbit disease. The purpose of this research is to make the application of rabbit disease diagnosis system so that can help user in taking care of rabbit. This application diagnoses the disease by tracing the symptoms and calculating the recommendation of the disease using Simple Additive Weighting method. This research produces a web-based decision support system that is used to help rabbit breeders and the general public.

A model of tumor architecture and spatial interactions with tumor microenvironment in breast carcinoma

Science.gov (United States)

Ben Cheikh, Bassem; Bor-Angelier, Catherine; Racoceanu, Daniel

2017-03-01

Breast carcinomas are cancers that arise from the epithelial cells of the breast, which are the cells that line the lobules and the lactiferous ducts. Breast carcinoma is the most common type of breast cancer and can be divided into different subtypes based on architectural features and growth patterns, recognized during a histopathological examination. Tumor microenvironment (TME) is the cellular environment in which tumor cells develop. Being composed of various cell types having different biological roles, TME is recognized as playing an important role in the progression of the disease. The architectural heterogeneity in breast carcinomas and the spatial interactions with TME are, to date, not well understood. Developing a spatial model of tumor architecture and spatial interactions with TME can advance our understanding of tumor heterogeneity. Furthermore, generating histological synthetic datasets can contribute to validating, and comparing analytical methods that are used in digital pathology. In this work, we propose a modeling method that applies to different breast carcinoma subtypes and TME spatial distributions based on mathematical morphology. The model is based on a few morphological parameters that give access to a large spectrum of breast tumor architectures and are able to differentiate in-situ ductal carcinomas (DCIS) and histological subtypes of invasive carcinomas such as ductal (IDC) and lobular carcinoma (ILC). In addition, a part of the parameters of the model controls the spatial distribution of TME relative to the tumor. The validation of the model has been performed by comparing morphological features between real and simulated images.

Mitigating Errors in External Respiratory Surrogate-Based Models of Tumor Position

Energy Technology Data Exchange (ETDEWEB)

Malinowski, Kathleen T. [Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD (United States); Fischell Department of Bioengineering, University of Maryland, College Park, MD (United States); McAvoy, Thomas J. [Fischell Department of Bioengineering, University of Maryland, College Park, MD (United States); Department of Chemical and Biomolecular Engineering and Institute of Systems Research, University of Maryland, College Park, MD (United States); George, Rohini [Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD (United States); Dieterich, Sonja [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA (United States); D' Souza, Warren D., E-mail: wdsou001@umaryland.edu [Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD (United States); Fischell Department of Bioengineering, University of Maryland, College Park, MD (United States)

2012-04-01

Purpose: To investigate the effect of tumor site, measurement precision, tumor-surrogate correlation, training data selection, model design, and interpatient and interfraction variations on the accuracy of external marker-based models of tumor position. Methods and Materials: Cyberknife Synchrony system log files comprising synchronously acquired positions of external markers and the tumor from 167 treatment fractions were analyzed. The accuracy of Synchrony, ordinary-least-squares regression, and partial-least-squares regression models for predicting the tumor position from the external markers was evaluated. The quantity and timing of the data used to build the predictive model were varied. The effects of tumor-surrogate correlation and the precision in both the tumor and the external surrogate position measurements were explored by adding noise to the data. Results: The tumor position prediction errors increased during the duration of a fraction. Increasing the training data quantities did not always lead to more accurate models. Adding uncorrelated noise to the external marker-based inputs degraded the tumor-surrogate correlation models by 16% for partial-least-squares and 57% for ordinary-least-squares. External marker and tumor position measurement errors led to tumor position prediction changes 0.3-3.6 times the magnitude of the measurement errors, varying widely with model algorithm. The tumor position prediction errors were significantly associated with the patient index but not with the fraction index or tumor site. Partial-least-squares was as accurate as Synchrony and more accurate than ordinary-least-squares. Conclusions: The accuracy of surrogate-based inferential models of tumor position was affected by all the investigated factors, except for the tumor site and fraction index.

Cloning and functional characterization of the rabbit C-C chemokine receptor 2

Directory of Open Access Journals (Sweden)

Hamdouchi Chafiq

2005-07-01

Full Text Available Abstract Background CC-family chemokine receptor 2 (CCR2 is implicated in the trafficking of blood-borne monocytes to sites of inflammation and is implicated in the pathogenesis of several inflammatory diseases such as rheumatoid arthritis, multiple sclerosis and atherosclerosis. The major challenge in the development of small molecule chemokine receptor antagonists is the lack of cross-species activity to the receptor in the preclinical species. Rabbit models have been widely used to study the role of various inflammatory molecules in the development of inflammatory processes. Therefore, in this study, we report the cloning and characterization of rabbit CCR2. Data regarding the activity of the CCR2 antagonist will provide valuable tools to perform toxicology and efficacy studies in the rabbit model. Results Sequence alignment indicated that rabbit CCR2 shares 80 % identity to human CCR2b. Tissue distribution indicated that rabbit CCR2 is abundantly expressed in spleen and lung. Recombinant rabbit CCR2 expressed as stable transfectants in U-937 cells binds radiolabeled 125I-mouse JE (murine MCP-1 with a calculated Kd of 0.1 nM. In competition binding assays, binding of radiolabeled mouse JE to rabbit CCR2 is differentially competed by human MCP-1, -2, -3 and -4, but not by RANTES, MIP-1α or MIP-1β. U-937/rabbit CCR2 stable transfectants undergo chemotaxis in response to both human MCP-1 and mouse JE with potencies comparable to those reported for human CCR2b. Finally, TAK-779, a dual CCR2/CCR5 antagonist effectively inhibits the binding of 125I-mouse JE (IC50 = 2.3 nM to rabbit CCR2 and effectively blocks CCR2-mediated chemotaxis. Conclusion In this study, we report the cloning of rabbit CCR2 and demonstrate that this receptor is a functional chemotactic receptor for MCP-1.

Anti-inflammatory effect of Heliotropium indicum Linn on lipopolysaccharide-induced uveitis in New Zealand white rabbits.

Science.gov (United States)

Kyei, Samuel; Koffuor, George Asumeng; Ramkissoon, Paul; Ameyaw, Elvis Ofori; Asiamah, Emmanuel Akomanin

2016-01-01

To investigate the anti-inflammatory effect of an aqueous whole plant extract of Heliotropium indicum (HIE) on endotoxin-induced uveitis in New Zealand white rabbits. Clinical signs of uveitis including flares, iris hyperemia and miosis, were sought for and scored in 1.0 mg/kg lipopolysaccharide (LPS) -induced uveitic rabbits treated orally with HIE (30-300 mg/kg), prednisolone (30 mg/kg), or normal saline (10 mL/kg). The number of polymorphonuclear neutrophils infiltrating, the protein concentration, as well as levels of tumor necrosis factor-α (TNF-α), prostaglandin E2 (PGE2), and monocyte chemmoattrant protein-1 (MCP-1) in the aqueous humor after the various treatments were also determined. A histopathological study of the anterior uveal was performed. The extract and prednisolone-treatment significantly reduced (P≤0.001) both the clinical scores of inflammation (1.0-1.8 compared to 4.40±0.40 in the normal saline-treated rabbits) and inflammatory cells infiltration. The level of protein, and the concentrations of TNF-α, PGE2 and MCP-1 in the aqueous humor were also significantly reduced (P≤0.001). Histopathological studies showed normal uveal morphology in the HIE and prednisolone-treated rabbits while normal saline-treated rabbits showed marked infiltration of inflammatory cells. The HIE exhibits anti-inflammatory effect on LPS-induced uveitis possibly by reducing the production of pro-inflammatory mediators.

AV-block and conduction slowing prevail over TdP arrhythmias in the methoxamine-sensitized pro-arrhythmic rabbit model

NARCIS (Netherlands)

Varkevisser, Rosanne; Vos, Marc A; Beekman, Jet; Tieland, Ralph G; Van Der Heyden, Marcel A

INTRODUCTION: The methoxamine-sensitized rabbit model is widely used to screen drugs for proarrhythmic properties, especially repolarization-dependent TdP arrhythmias. With the change of anesthesia and/or sensitizing agent, conduction disturbances have been reported as well. Therefore, we compared

Efficacy of peroxisome proliferator activated receptor agonist in the treatment of virus-associated haemophagocytic syndrome in a rabbit model.

Science.gov (United States)

Hsieh, Wen-Chuan; Lan, Bau-Shin; Chen, Yi-Ling; Chang, Yao; Chuang, Huai-Chia; Su, Ih-Jen

2010-01-01

Virus-associated haemophagocytic syndrome (VAHS) is a fatal complication of viral infections, such as Epstein-Barr virus and H5N1 influenza, that results from macrophage activation and pro inflammatory cytokine injuries. The high comorbidity and mortality of current therapy urgently demands an ideal agent based on VAHS pathogenesis. Peroxisome proliferator activated receptor (PPAR) agonists, regulators of metabolic syndrome, can exhibit immunomodulatory effects on macrophage activation and cytokine secretion. In this study, we adopted rosiglitazone, a PPAR-gamma agonist, for VAHS control in a Herpesvirus papio (HVP)-infected rabbit model. Various doses of rosiglitazone were orally administered to rabbits on day 7 or day 20 after intravenous challenge with 5 x 10(7) copies of HVP. The rabbits that received 4 mg/day rosiglitazone had significantly increased survival when treated at an early stage of infection (P<0.01), whereas a higher dose (8 mg/day) was required at the advanced stage of the disease (P<0.05). All rosiglitazone-treated rabbits had significantly improved laboratory parameters and plasma tumour necrosis factor-alpha levels. Importantly, rosiglitazone could also inhibit viral replication in vitro and in vivo. PPAR agonists could represent a potentially new agent for the therapy of VAHS.

Skull base tumor model.

Science.gov (United States)

Gragnaniello, Cristian; Nader, Remi; van Doormaal, Tristan; Kamel, Mahmoud; Voormolen, Eduard H J; Lasio, Giovanni; Aboud, Emad; Regli, Luca; Tulleken, Cornelius A F; Al-Mefty, Ossama

2010-11-01

Resident duty-hours restrictions have now been instituted in many countries worldwide. Shortened training times and increased public scrutiny of surgical competency have led to a move away from the traditional apprenticeship model of training. The development of educational models for brain anatomy is a fascinating innovation allowing neurosurgeons to train without the need to practice on real patients and it may be a solution to achieve competency within a shortened training period. The authors describe the use of Stratathane resin ST-504 polymer (SRSP), which is inserted at different intracranial locations to closely mimic meningiomas and other pathological entities of the skull base, in a cadaveric model, for use in neurosurgical training. Silicone-injected and pressurized cadaveric heads were used for studying the SRSP model. The SRSP presents unique intrinsic metamorphic characteristics: liquid at first, it expands and foams when injected into the desired area of the brain, forming a solid tumorlike structure. The authors injected SRSP via different passages that did not influence routes used for the surgical approach for resection of the simulated lesion. For example, SRSP injection routes included endonasal transsphenoidal or transoral approaches if lesions were to be removed through standard skull base approach, or, alternatively, SRSP was injected via a cranial approach if the removal was planned to be via the transsphenoidal or transoral route. The model was set in place in 3 countries (US, Italy, and The Netherlands), and a pool of 13 physicians from 4 different institutions (all surgeons and surgeons in training) participated in evaluating it and provided feedback. All 13 evaluating physicians had overall positive impressions of the model. The overall score on 9 components evaluated--including comparison between the tumor model and real tumor cases, perioperative requirements, general impression, and applicability--was 88% (100% being the best possible

X-Ray structure and biophysical properties of rabbit fibroblast growth factor 1

Energy Technology Data Exchange (ETDEWEB)

Lee, Jihun; Blaber, Sachiko I.; Irsigler, Andre; Aspinwall, Eric; Blaber, Michael; (FSU)

2010-01-14

The rabbit is an important and de facto animal model in the study of ischemic disease and angiogenic therapy. Additionally, fibroblast growth factor 1 (FGF-1) is emerging as one of the most important growth factors for novel pro-angiogenic and pro-arteriogenic therapy. However, despite its significance, the fundamental biophysical properties of rabbit FGF-1, including its X-ray structure, have never been reported. Here, the cloning, crystallization, X-ray structure and determination of the biophysical properties of rabbit FGF-1 are described. The X-ray structure shows that the amino-acid differences between human and rabbit FGF-1 are solvent-exposed and therefore potentially immunogenic, while the biophysical studies identify differences in thermostability and receptor-binding affinity that distinguish rabbit FGF-1 from human FGF-1.

Effect of cyclic training model on terminal structure of rabbit Achilles tendon: an experimental study

OpenAIRE

Chang-lin HUANG; Wang GAO; Tao HUANG; Zhen-hai GUO

2012-01-01

Objective 　To observe the effect of cyclic training on histomorphology of the terminal structure of rabbit Achilles tendon, and explore its preventive effect on training-based enthesiopathy. Methods 　Seventy-two Japanese white rabbits were randomly assigned to four groups: control group, jumping group, running group and cyclic training group, 18 for each. Three rabbits of each group were sacrificed at the 2nd, 3rd, 4th, 6th, 8th and 10th week. The terminal insertion tissues of bilateral Achil...

Flagella-induced immunity against experimental cholera in adult rabbits.

Science.gov (United States)

Yancey, R J; Willis, D L; Berry, L J

1979-07-01

The adult rabbit ligated ileal loop model was used to evaluate the prophylactic potential of a crude flagellar (CF) vaccine produced from the classical. Inaba strain CA401. A greater than 1,000-fold increase in the challenge inoculum was required to induce an intestinal fluid response in actively immunized adult rabbits equivalent to that produced in unimmunized animals. Similar protection was afforded against challenge with classical and El Tor biotypes of both Inaba and Ogawa serotypes. Highly virulent 35S-labeled vibrios were inhibited in their ability to associated with the intestinal mucosa of CF-immunized rabbits. The protection conferred by CF immunization was found to be superior to that of a commercial bivalent vaccine and also to that of glutaraldehyde-treated cholera toxoid. The critical immunogenic component of CF appears to be a flagella-derived protein. The immunogenicity of CF was destroyed by heat treatment, and absorption of CF-immune serum with aflagellated mutant vibrios did not diminish its ability to confer a high level of passive protection. The intestinal protection of CF-immunized rabbits was completely reversed by the introduction of both goat anti-rabbit immunoglobulins A and G, but by neither alone.

Attenuated ventricular β-adrenergic response and reduced repolarization reserve in a rabbit model of chronic heart failure

DEFF Research Database (Denmark)

Nissen, Jakob Dahl; Thomsen, Morten Bækgaard; Bentzen, Bo Hjorth

2012-01-01

Animal models of pacing-induced heart failure (HF) are often associated with high acute mortality secondary to high pacing frequencies. The present study therefore exploits lower-frequency left ventricular pacing (300 beats per minute) in rabbits for 11 weeks to produce chronic HF with low acute...... mortality but profound structural, functional, and electrical remodeling and compare with nonpaced controls. Pacing increased heart weight/body weight ratio and decreased left ventricular fractional shortening in tachypaced only. Electrocardiogram recordings during sinus rhythm revealed QTc prolongation...... in paced animals. Ventricular arrhythmias or sudden death was not observed. Isoproterenol increased heart rate similarly in both groups but showed a blunted QT-shortening effect in tachypaced rabbits compared with controls. Langendorff experiments revealed significant monophasic action potential duration...

The Streptococcus sanguinis competence regulon is not required for infective endocarditis virulence in a rabbit model.

Science.gov (United States)

Callahan, Jill E; Munro, Cindy L; Kitten, Todd

2011-01-01

Streptococcus sanguinis is an important component of dental plaque and a leading cause of infective endocarditis. Genetic competence in S. sanguinis requires a quorum sensing system encoded by the early comCDE genes, as well as late genes controlled by the alternative sigma factor, ComX. Previous studies of Streptococcus pneumoniae and Streptococcus mutans have identified functions for the >100-gene com regulon in addition to DNA uptake, including virulence. We investigated this possibility in S. sanguinis. Strains deleted for the comCDE or comX master regulatory genes were created. Using a rabbit endocarditis model in conjunction with a variety of virulence assays, we determined that both mutants possessed infectivity equivalent to that of a virulent control strain, and that measures of disease were similar in rabbits infected with each strain. These results suggest that the com regulon is not required for S. sanguinis infective endocarditis virulence in this model. We propose that the different roles of the S. sanguinis, S. pneumoniae, and S. mutans com regulons in virulence can be understood in relation to the pathogenic mechanisms employed by each species.

Coccidian and nematode infections influence prevalence of antibody to myxoma and rabbit hemorrhagic disease viruses in European rabbits.

Science.gov (United States)

Bertó-Moran, Alejandro; Pacios, Isabel; Serrano, Emmanuel; Moreno, Sacramento; Rouco, Carlos

2013-01-01

The interaction among several parasites in European rabbits (Oryctolagus cuniculus) is crucial to host fitness and to the epidemiology of myxomatosis and rabbit hemorrhagic disease. These diseases have caused significant reductions in rabbit populations on the Iberian Peninsula. Most studies have focused on the epidemiology and pathogenesis of these viruses individually, and little is known about interactions between these viruses and other parasites. Taking advantage of an experimental restocking program in Spain, the effects of coccidian and nematode infections on the probability of having detectable antibody to myxoma and rabbit hemorrhagic disease viruses were tested in European wild rabbits. For 14 mo, we monitored rabbit abundance and parasite loads (coccidia and nematodes) in three reintroduced rabbit populations. While coccidian and nematode loads explained seasonal antibody prevalences to myxoma virus, the pattern was less clear for rabbit hemorrhagic disease. Contrary to expectations, prevalence of antibody to myxoma virus was inversely proportional to coccidian load, while nematode load seemed to play a minor role. These results have implications for viral disease epidemiology and for disease management intended to increase rabbit populations in areas where they are important for ecosystem conservation.

Assessment of ABCG2-mediated transport of pesticides across the rabbit placenta barrier using a novel MDCKII in vitro model

International Nuclear Information System (INIS)

Halwachs, Sandra; Schäfer, Ingo; Kneuer, Carsten; Seibel, Peter; Honscha, Walther

2016-01-01

In humans, the ATP-binding cassette efflux transporter ABCG2 contributes to the fetoprotective barrier function of the placenta, potentially limiting the toxicity of transporter substrates to the fetus. During testing of chemicals including pesticides, developmental toxicity studies are performed in rabbit. Despite its toxicological relevance, ABCG2-mediated transport of pesticides in rabbit placenta has not been yet elucidated. We therefore generated polarized MDCK II cells expressing the ABCG2 transporter from rabbit placenta (rbABCG2) and evaluated interaction of the efflux transporter with selected insecticides, fungicides, and herbicides. The Hoechst H33342 accumulation assay indicated that 13 widely used pesticidal active substances including azoxystrobin, carbendazim, chlorpyrifos, chlormequat, diflufenican, dimethoate, dimethomorph, dithianon, ioxynil, methiocarb, propamocarb, rimsulfuron and toclofos-methyl may be rbABCG2 inhibitors and/or substrates. No such evidence was obtained for chlorpyrifos-methyl, epoxiconazole, glyphosate, imazalil and thiacloprid. Moreover, chlorpyrifos (CPF), dimethomorph, tolclofos-methyl and rimsulfuron showed concentration-dependent inhibition of H33342 excretion in rbABCG2-transduced MDCKII cells. To further evaluate the role of rbABCG2 in pesticide transport across the placenta barrier, we generated polarized MDCKII-rbABCG2 monolayers. Confocal microscopy confirmed correct localization of rbABCG2 protein in the apical plasma membrane. In transepithelial flux studies, we showed the time-dependent preferential basolateral to apical (B > A) directed transport of [ 14 C] CPF across polarized MDCKII-rbABCG2 monolayers which was significantly inhibited by the ABCG2 inhibitor fumitremorgin C (FTC). Using this novel in vitro cell culture model, we altogether showed functional secretory activity of the ABCG2 transporter from rabbit placenta and identified several pesticides like the insecticide CPF as potential rbABCG2 substrates

Assessment of ABCG2-mediated transport of pesticides across the rabbit placenta barrier using a novel MDCKII in vitro model

Energy Technology Data Exchange (ETDEWEB)

Halwachs, Sandra [Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, Universität Leipzig, Leipzig (Germany); Schäfer, Ingo [Molecular Cell Therapy, Center for Biotechnology and Biomedicine, Faculty of Medicine, Universität Leipzig, Leipzig (Germany); Kneuer, Carsten [Federal Institute for Risk Assessment (BfR), Pesticide Safety, Max-Dohrn-Straße 8-10, D-10589 Berlin (Germany); Seibel, Peter [Molecular Cell Therapy, Center for Biotechnology and Biomedicine, Faculty of Medicine, Universität Leipzig, Leipzig (Germany); Honscha, Walther, E-mail: honscha@vetmed.uni-leipzig.de [Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, Universität Leipzig, Leipzig (Germany)

2016-08-15

In humans, the ATP-binding cassette efflux transporter ABCG2 contributes to the fetoprotective barrier function of the placenta, potentially limiting the toxicity of transporter substrates to the fetus. During testing of chemicals including pesticides, developmental toxicity studies are performed in rabbit. Despite its toxicological relevance, ABCG2-mediated transport of pesticides in rabbit placenta has not been yet elucidated. We therefore generated polarized MDCK II cells expressing the ABCG2 transporter from rabbit placenta (rbABCG2) and evaluated interaction of the efflux transporter with selected insecticides, fungicides, and herbicides. The Hoechst H33342 accumulation assay indicated that 13 widely used pesticidal active substances including azoxystrobin, carbendazim, chlorpyrifos, chlormequat, diflufenican, dimethoate, dimethomorph, dithianon, ioxynil, methiocarb, propamocarb, rimsulfuron and toclofos-methyl may be rbABCG2 inhibitors and/or substrates. No such evidence was obtained for chlorpyrifos-methyl, epoxiconazole, glyphosate, imazalil and thiacloprid. Moreover, chlorpyrifos (CPF), dimethomorph, tolclofos-methyl and rimsulfuron showed concentration-dependent inhibition of H33342 excretion in rbABCG2-transduced MDCKII cells. To further evaluate the role of rbABCG2 in pesticide transport across the placenta barrier, we generated polarized MDCKII-rbABCG2 monolayers. Confocal microscopy confirmed correct localization of rbABCG2 protein in the apical plasma membrane. In transepithelial flux studies, we showed the time-dependent preferential basolateral to apical (B > A) directed transport of [{sup 14}C] CPF across polarized MDCKII-rbABCG2 monolayers which was significantly inhibited by the ABCG2 inhibitor fumitremorgin C (FTC). Using this novel in vitro cell culture model, we altogether showed functional secretory activity of the ABCG2 transporter from rabbit placenta and identified several pesticides like the insecticide CPF as potential rbABCG2

Enhanced Tendon-to-Bone Healing of Chronic Rotator Cuff Tears by Bone Marrow Aspirate Concentrate in a Rabbit Model

Science.gov (United States)

Liu, Xiao Ning; Yang, Cheol-Jung; Kim, Ji Eui; Du, Zhen Wu; Ren, Ming; Zhang, Wei; Zhao, Hong Yu; Kim, Kyung Ok

2018-01-01

Background To evaluate the influence of bone marrow aspirate concentrate (BMAC) on tendon-to-bone healing in a rabbit rotator cuff model and to characterize the composition of growth factors in BMAC. Methods In this in vivo study, 40 rabbits were allocated into five groups: control (C), repair + saline (RS), repair + platelet-rich plasma (PRP; RP), repair + BMAC (RB) and repair + PRP + BMAC (RPB). A tear model was created by supraspinatus tendon transection at the footprint. Six weeks after transection, the torn tendon was repaired along with BMAC or PRP administration. Six weeks after repair, shoulder samples were harvested for biomechanical and histological testing. Ten rabbits were used for processing PRP and BMAC, followed by analysis of blood cell composition and the levels of growth factors in vitro. Results The ultimate load-to-failure was significantly higher in RPB group compared to RS group (p = 0.025). BMAC-treated groups showed higher values of biomechanical properties than RS group. The histology of BMAC-treated samples showed better collagen fiber continuity and orientation than RS group. BMAC contained significantly higher levels of the several growth factors than PRP. Conclusions Locally administered BMAC enhanced tendon-to-bone healing and has potential for clinical applications. PMID:29564054

Expression of rabbit IL-4 by recombinant myxoma viruses enhances virulence and overcomes genetic resistance to myxomatosis.

Science.gov (United States)

Kerr, P J; Perkins, H D; Inglis, B; Stagg, R; McLaughlin, E; Collins, S V; Van Leeuwen, B H

2004-06-20

Rabbit IL-4 was expressed in the virulent standard laboratory strain (SLS) and the attenuated Uriarra (Ur) strain of myxoma virus with the aim of creating a Th2 cytokine environment and inhibiting the development of an antiviral cell-mediated response to myxomatosis in infected rabbits. This allowed testing of a model for genetic resistance to myxomatosis in wild rabbits that have undergone 50 years of natural selection for resistance to myxomatosis. Expression of IL-4 significantly enhanced virulence of both virulent and attenuated virus strains in susceptible (laboratory) and resistant (wild) rabbits. SLS-IL-4 completely overcame genetic resistance in wild rabbits. The pathogenesis of SLS-IL-4 was compared in susceptible and resistant rabbits. The results support a model for resistance to myxomatosis of an enhanced innate immune response controlling virus replication and allowing an effective antiviral cell-mediated immune response to develop in resistant rabbits. Expression of IL-4 did not overcome immunity to myxomatosis induced by immunization.

Prostaglandin synthesis and catabolism in the gastric mucosa: studies in normal rabbits and rabbits immunized with prostaglandin E2

International Nuclear Information System (INIS)

Redfern, J.S.

1988-01-01

Antral and fundic mucosal homogenates obtained from prostaglandin E2-immunized rabbits converted 14C-arachidonic acid to prostaglandin E2, 6-keto prostaglandin F1 alpha, prostaglandin F2 alpha, and prostaglandin D2. Percentage conversion of 14C-arachidonic acid to these prostaglandin products was not significantly different in prostaglandin E2-immunized rabbits compared with control rabbits (thyroglobulin-immunized and unimmunized rabbits combined). Synthesis of 6-keto prostaglandin F1 alpha, prostaglandin E2 and 13,14-dihydro 15-keto prostaglandin E2 from endogenous arachidonic acid after vortex mixing fundic mucosal homogenates was similar in prostaglandin E2 immunized rabbits and control rabbits. Both in prostaglandin E2-immunized rabbits and controls, 3H-prostaglandin E2 was catabolized extensively by the fundic mucosa, whereas 3H-6-keto prostaglandin F1 alpha, 3H-prostaglandin F2 alpha, and 3H-prostaglandin D2 were not catabolized to any appreciable extent. The rate of catabolism of PGs was not significantly different in prostaglandin E2-immunized rabbits and control rabbits, with the exception of prostaglandin F2 alpha which was catabolized slightly more rapidly in prostaglandin E2-immunized rabbits. These results indicate that development of gastric ulcers in prostaglandin E2-immunized rabbits is not associated with an alteration in the capacity of the gastric mucosa to synthesize or catabolize prostaglandins

Dermatophytes in pet Guinea pigs and rabbits.

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Kraemer, A; Mueller, R S; Werckenthin, C; Straubinger, R K; Hein, J

2012-05-25

The frequency of dermatophytes in pet Guinea pigs and rabbits. To determine the frequency and types of dermatophytes in pet Guinea pigs and rabbits. First, 2153 samples collected from pet Guinea pigs (n=1132) and rabbits (n=1021) with suspected dermatophytosis and submitted to three different laboratories for fungal culture were analysed. Subsequently, healthy Guinea pigs and rabbits, animals with skin lesions and with noncutaneous diseases were examined prospectively for dermatophytes. Trichophyton (T.) mentagrophytes was the most common fungal species isolated (91.6% and 72.3% of positive cultures from Guinea pigs (n=431) and rabbits (n=83), respectively). Animals with positive fungal culture did not show any gender predisposition, but affected animals were younger than those with negative fungal culture (PGuinea pigs and 0/140 healthy rabbits. In addition, fungal cultures of Guinea pigs with skin lesions (n=26) and other diseases (n=25) were positive in 7.7% and 8.0% respectively. Samples collected from 17 rabbits with skin lesions and 32 rabbits with noncutaneous disease were all negative in culture. T. mentagrophytes is the most common dermatophyte in pet Guinea pigs and rabbits, asymptomatic carriers are regularly seen in Guinea pigs, but not in rabbits. Copyright © 2011 Elsevier B.V. All rights reserved.

Classification of rabbit meat obtained with industrial and organic breeding by means of spectrocolorimetric technique

Science.gov (United States)

Menesatti, P.; D'Andrea, S.; Negretti, P.

2007-09-01

Rabbit meat is for its nutritional characteristics a food corresponding to new models of consumption. Quality improvement is possible integrating an extensive organic breeding with suitable rabbit genetic typologies. Aim of this work (financed by a Project of the Lazio Region, Italy) was the characterization of rabbit meat by a statistic model, able to distinguish rabbit meat obtained by organic breeding from that achieved industrially. This was pursued through the analysis of spectral data and colorimetric values. Two genetic typologies of rabbit, Leprino Viterbese and a commercial hybrid, were studied. The Leprino Viterbese has been breeded with two different systems, organic and industrial. The commercial hybrid has been bred only industrially because of its characteristics of high sensibility to diseases. The device used for opto-electronic analysis is a VIS-NIR image spectrometer (range: 400-970 nm). The instrument has a stabilized light, it works in accordance to standard CIE L*a*b* technique and it measures the spectral reflectance and the colorimetric coordinates values. The statistic data analysis has been performed by Partial Least Square technique (PLS). A part of measured data was used to create the statistic model and the remaining data were utilized in phase of test to verify the correct model classification. The results put in evidence a high percentage of correct classification (90%) of the model for the two rabbit meat classes, deriving from organic and industrial breeding. Moreover, concerning the different genetic typologies, the percentage of correct classification was 90%.

Evidence-Based Advances in Rabbit Medicine.

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Summa, Noémie M; Brandão, João

2017-09-01

Rabbit medicine has been continuously evolving over time with increasing popularity and demand. Tremendous advances have been made in rabbit medicine over the past 5 years, including the use of imaging tools for otitis and dental disease management, the development of laboratory testing for encephalitozoonosis, or determination of prognosis in rabbits. Recent pharmacokinetic studies have been published, providing additional information on commonly used antibiotics and motility-enhancer drugs, as well as benzimidazole toxicosis. This article presents a review of evidence-based advances for liver lobe torsions, thymoma, and dental disease in rabbits and controversial and new future promising areas in rabbit medicine. Copyright © 2017 Elsevier Inc. All rights reserved.

Investigation of the relationship between venticular fibrillation duration and cardiac/neurological damage in a rabbit model of electrically induced arrhythmia.

Science.gov (United States)

Hu, Chun-Lin; Wei, Hong-Yan; Liu, Zi-You; Li, Xing; Liao, Xiao-Xing; Li, Yu-Jie; Zhan, Hong; Jing, Xiao-Li; Xiong, Yan; Liu, Yan-Yan; Wu, Gui-Fu

2010-12-01

To establish a simple, economic, and reliable alternating current (AC)-induced cardiac arrest (ACCA) model in rabbits for cardiopulmonary cerebral resuscitation research. Ventricular fibrillation was induced in 27 New Zealand rabbits by external transthoracic AC, which were randomly divided into three groups according to the duration of untreated ACCA (ACCA-3 minutes, ACCA-5 minutes, and ACCA-8 minutes). After ACCA, all animals received cardiopulmonary resuscitation for 2 minutes and subsequent defibrillation until return of spontaneous circulation (ROSC). The troponin I levels were measured at 4 hours after ROSC. Animals died spontaneously or were killed at 72 hours after ROSC. The hippocampus were removed and fixed in 3% formalin. TdT-mediated dUTP-biotin nick end labeling and Nissl stainings were performed in 10-μm thickness coronal sections. Furthermore, two rabbits (without induction of ventricular fibrillation, cardiopulmonary resuscitation, and defibrillation) served as normal control group. Mean survival times after ROSC were 48.57 hours ± 24.70 hours, 18.0 hours ± 15.13 hours, and 3.88 hours ± 2.39 hours for groups ACCA-3 minutes, ACCA-5 minutes, and ACCA-8 minutes, respectively. Survival was significantly different between ACCA-3 minutes and other two groups (p = 0.002 and p = 0.01). Neuronal necrosis and apoptosis were found in the hippocampus CA1, CA2, and CA3 areas of group ACCA-3 minutes. In contrast, neuronal necrosis and TdT-mediated dUTP-biotin nick end labeling positive cells were fewer in control animals. The rabbits in group ACCA-3 minutes had significant neuronal damage with apoptosis in hippocampus CA1, CA2, and CA3 areas at 72 hours after ROSC and survived longer than those in other groups. The model we describe may be a simple, economic, and reliable model for experimental investigation on cardiopulmonary cerebral resuscitation.

Coupled Hybrid Continuum-Discrete Model of Tumor Angiogenesis and Growth.

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Jie Lyu

Full Text Available The processes governing tumor growth and angiogenesis are codependent. To study the relationship between them, we proposed a coupled hybrid continuum-discrete model. In this model, tumor cells, their microenvironment (extracellular matrixes, matrix-degrading enzymes, and tumor angiogenic factors, and their network of blood vessels, described by a series of discrete points, were considered. The results of numerical simulation reveal the process of tumor growth and the change in microenvironment from avascular to vascular stage, indicating that the network of blood vessels develops gradually as the tumor grows. Our findings also reveal that a tumor is divided into three regions: necrotic, semi-necrotic, and well-vascularized. The results agree well with the previous relevant studies and physiological facts, and this model represents a platform for further investigations of tumor therapy.

Cyclosporin safety in a simplified rat brain tumor implantation model

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Francisco H. C. Felix

2012-01-01

Full Text Available Brain cancer is the second neurological cause of death. A simplified animal brain tumor model using W256 (carcinoma 256, Walker cell line was developed to permit the testing of novel treatment modalities. Wistar rats had a cell tumor solution inoculated stereotactically in the basal ganglia (right subfrontal caudate. This model yielded tumor growth in 95% of the animals, and showed absence of extracranial metastasis and systemic infection. Survival median was 10 days. Estimated tumor volume was 17.08±6.7 mm³ on the 7th day and 67.25±19.8 mm³ on 9th day post-inoculation. Doubling time was 24.25 h. Tumor growth induced cachexia, but no hematological or biochemical alterations. This model behaved as an undifferentiated tumor and can be promising for studying tumor cell migration in the central nervous system. Dexamethasone 3.0 mg/kg/day diminished significantly survival in this model. Cyclosporine 10 mg/kg/day administration was safely tolerated.

Is there a difference between hare syphilis and rabbit syphilis? Cross infection experiments between rabbits and hares

NARCIS (Netherlands)

Lumeij, J.T.|info:eu-repo/dai/nl/073286826; Mikalová, L.; Smajs, D.

2013-01-01

Abstract Cross infection of rabbits and hares with Treponema paraluiscuniculi from rabbits and the related microorganism from hares, which was provisionally named "Treponema paraluisleporis", revealed that T. paraluiscuniculi affects rabbits clinically, but only causes seroconversion in hares

Preliminary study of rabbit model with corneal neovascularization after thermal burn under the constant temperature

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Yong Jia

2014-07-01

Full Text Available AIM:To explore the suitable conditions in rapid model of corneal neovascularization(CNVafter thermal burn under different constant temperature in rabbit. METHODS: Total 45 New Zealand white rabbits were divided randomly into five groups(A, B, C, D, E. A groups: 100℃(n=10, B groups: 200℃(n=10, C groups: 300℃(n=10, D groups: 400℃(n=10, and E groups: control group(n=5. All left eyes of rabbits in A,B,C,D groups were induced corneal neovascularization by constant temperature burning device. The growth of CNV was observed by slit lamp microscope and the area of CNV were recorded on 4 th, 7 th, 14th, 30th days postoperatively. SPSS 19.0 statistical package was used for data analysis, and the data was recorded by mean±standard deviation. Comparison by analysis of variance was made by repeated measures in the area of neovascularization at each time point in groups. Statistical tests were considered significantly when P values were less than 0.05. RESULTS: On postoperative 4th, 7th, 14th, 30th days: no neovascularization was found after corneal thermal burn in A group, but only a few nebula left(n=2; the area of CNV were(9.16±1.45mm2,(37.73±5.49mm2,(62.44±7.54mm2,(40.28±7.39mm2 in B group respectively; and(11.45±1.04mm2,(44.51±4.64mm2,(66.13±4.13mm2,(43.04±2.33mm2 in C group respectively; and(13.23±0.86mm2,(47.26±4.59mm2,(67.57±4.56mm2,(45.59±4.44mm2 in D group respectively, and part corneal carbide(n=4was observed as well as corneal perforation(n=6were found on 3d in D group. No neovascularization was found in normal control group. Comparison of the areas of CNV at each time point between groups was statistically different, PPCOCLUSION: In 4 to 7d, the higher the temperature is, the more the neovascularization area of CNV are. It has no significant difference in 14 to 30d. But corneal carbide and corneal perforation are often found in 400℃ group, so its modeling failure rate is high. It is between 200℃ and 300℃ that

Antioxidant and anti-inflammatory effects of cauliflower leaf powder-enriched diet against LPS induced toxicity in rabbits.

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Larocca, Marilena; Perna, Anna Maria; Simonetti, Amalia; Gambacorta, Emilio; Iannuzzi, Alessandra; Perucatti, Angela; Rossano, Rocco

2017-09-20

Brassica phytochemicals exert a broad spectrum of health-promoting activities. The aim of this study was to investigate the possible beneficial effects of a cauliflower leaf powder (CLP)-enriched diet to prevent inflammation and oxidative stress resulting from injection of lipopolysaccharide (LPS) into rabbits. Animals (24 rabbits) were randomly divided into two groups and fed with a standard diet (SD) or a standard diet supplemented with a 100 g kg -1 diet of CLP. After 60 days, six rabbits of both groups received a LPS injection (100 μg per kg body weight). Serum samples collected after 90 min of LPS injection were assessed for their content of both inflammatory biomarkers such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and matrix-metalloproteinases (MMP-2 and MMP-9) and oxidative stress biomarkers such as thiobarbituric acid reactive substances (TBARS), glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT). LPS increased the levels of TNF-α, IL-6, and TBARS as well as MMP-2 and MMP-9 activities, whereas it decreased the GSH levels and SOD and CAT activities. In conclusion, preventive supplementation with CLP can protect rabbits from the inflammation and oxidative stress induced by LPS.

Evaluation of 99mTc-Labeled Bevacizumab-N-HYNIC Conjugate in Human Ovarian Tumor Xenografts.

Science.gov (United States)

Shah, Syed Qaiser; Mahmood, Samia

2018-03-20

The aim of the present investigation was to examine the suitability of 99m Tc-N-HYNIC-BZMB as a specific vascular endothelial growth factor (VEGF)-targeting agent. Bevacizumab is a recombinant humanized monoclonal antibody that inhibits VEGF. N-hydroxysuccinimide-2-hydrazinonicotinic acid (N-HYNIC) was conjugated to BZMB, followed by labeling with 99m Tc using N-[Tris(hydroxymethyl)methyl] glycine (tricine), ethylenediamine-N,N'-diacetic acid (EDDA), and nicotinic acid as coligands. 99m Tc-labeled BZMB was characterized in terms of 99m TcO 4 , radiocolloids, and labeled N-HYNIC-BZMB using thin-layer chromatography and HPLC. Poor metastatic SKOV-3 and high metastatic SKOV-3.ip1 human ovarian cancer cell lines were used for in vitro binding uptake of 99m Tc-N-HYNIC-BZMB. Biodistribution and scintigraphy accuracy were examined in human ovarian tumor xenografts in rats and rabbits. 99m Tc-N-HYNIC-BZMB prepared by using a mixture of tricine and EDDA demonstrated relatively high radiochemical purity (more than 98%). In L-cysteine and serum, it exhibited a stable behavior up to 16 hours. In vitro binding uptake indicated that it targets high metastatic SKOV-3.ip1 tumors. Biodistribution in human ovarian tumor xenografts in rats confirmed a significant uptake in SKOV-3.ip1 tumors (5.69% ± 1.86%, 4 hours). Scintigraphic accuracy in human ovarian tumor xenografts in rabbits validated its suitability as a high metastatic SKOV-3.ip1 radiotracer. High radiochemical purity, stability in saline and serum, biodistribution, and scintigraphy of 99m Tc-N-HYNIC-BZMB in human ovarian tumor xenografts in rats and rabbits confirmed its suitability as a potential radiotracer for imaging high metastatic SKOV-3.ip1 sites.

A Rabbit Model for Testing Helper-Dependent Adenovirus-Mediated Gene Therapy for Vein Graft Atherosclerosis

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Lianxiang Bi

2017-12-01

Full Text Available Coronary artery bypass vein grafts are a mainstay of therapy for human atherosclerosis. Unfortunately, the long-term patency of vein grafts is limited by accelerated atherosclerosis. Gene therapy, directed at the vein graft wall, is a promising approach for preventing vein graft atherosclerosis. Because helper-dependent adenovirus (HDAd efficiently transduces grafted veins and confers long-term transgene expression, HDAd is an excellent candidate for delivery of vein graft-targeted gene therapy. We developed a model of vein graft atherosclerosis in fat-fed rabbits and demonstrated long-term (≥20 weeks persistence of HDAd genomes after graft transduction. This model enables quantitation of vein graft hemodynamics, wall structure, lipid accumulation, cellularity, vector persistence, and inflammatory markers on a single graft. Time-course experiments identified 12 weeks after transduction as an optimal time to measure efficacy of gene therapy on the critical variables of lipid and macrophage accumulation. We also used chow-fed rabbits to test whether HDAd infusion in vein grafts promotes intimal growth and inflammation. HDAd did not increase intimal growth, but had moderate—yet significant—pro-inflammatory effects. The vein graft atherosclerosis model will be useful for testing HDAd-mediated gene therapy; however, pro-inflammatory effects of HdAd remain a concern in developing HDAd as a therapy for vein graft disease.

Mitigating Errors in External Respiratory Surrogate-Based Models of Tumor Position

International Nuclear Information System (INIS)

Malinowski, Kathleen T.; McAvoy, Thomas J.; George, Rohini; Dieterich, Sonja; D'Souza, Warren D.

2012-01-01

Purpose: To investigate the effect of tumor site, measurement precision, tumor–surrogate correlation, training data selection, model design, and interpatient and interfraction variations on the accuracy of external marker-based models of tumor position. Methods and Materials: Cyberknife Synchrony system log files comprising synchronously acquired positions of external markers and the tumor from 167 treatment fractions were analyzed. The accuracy of Synchrony, ordinary-least-squares regression, and partial-least-squares regression models for predicting the tumor position from the external markers was evaluated. The quantity and timing of the data used to build the predictive model were varied. The effects of tumor–surrogate correlation and the precision in both the tumor and the external surrogate position measurements were explored by adding noise to the data. Results: The tumor position prediction errors increased during the duration of a fraction. Increasing the training data quantities did not always lead to more accurate models. Adding uncorrelated noise to the external marker-based inputs degraded the tumor–surrogate correlation models by 16% for partial-least-squares and 57% for ordinary-least-squares. External marker and tumor position measurement errors led to tumor position prediction changes 0.3–3.6 times the magnitude of the measurement errors, varying widely with model algorithm. The tumor position prediction errors were significantly associated with the patient index but not with the fraction index or tumor site. Partial-least-squares was as accurate as Synchrony and more accurate than ordinary-least-squares. Conclusions: The accuracy of surrogate-based inferential models of tumor position was affected by all the investigated factors, except for the tumor site and fraction index.

Subunit Rotavirus Vaccine Administered Parenterally to Rabbits Induces Active Protective Immunity

Science.gov (United States)

Ciarlet, Max; Crawford, Sue E.; Barone, Christopher; Bertolotti-Ciarlet, Andrea; Ramig, Robert F.; Estes, Mary K.; Conner, Margaret E.

1998-01-01

Virus-like particles (VLPs) are being evaluated as a candidate rotavirus vaccine. The immunogenicity and protective efficacy of different formulations of VLPs administered parenterally to rabbits were tested. Two doses of VLPs (2/6-, G3 2/6/7-, or P[2], G3 2/4/6/7-VLPs) or SA11 simian rotavirus in Freund’s adjuvants, QS-21 (saponin adjuvant), or aluminum phosphate (AlP) were administered. Serological and mucosal immune responses were evaluated in all vaccinated and control rabbits before and after oral challenge with 103 50% infective doses of live P[14], G3 ALA lapine rotavirus. All VLP- and SA11-vaccinated rabbits developed high levels of rotavirus-specific serum and intestinal immunoglobulin G (IgG) antibodies but not intestinal IgA antibodies. SA11 and 2/4/6/7-VLPs afforded similar but much higher mean levels of protection than 2/6/7- or 2/6-VLPs in QS-21. The presence of neutralizing antibodies to VP4 correlated (P < 0.001, r = 0.55; Pearson’s correlation coefficient) with enhanced protection rates, suggesting that these antibodies are important for protection. Although the inclusion of VP4 resulted in higher mean protection levels, high levels of protection (87 to 100%) from infection were observed in individual rabbits immunized with 2/6/7- or 2/6-VLPs in Freund’s adjuvants. Therefore, neither VP7 nor VP4 was absolutely required to achieve protection from infection in the rabbit model when Freund’s adjuvant was used. Our results show that VLPs are immunogenic when administered parenterally to rabbits and that Freund’s adjuvant is a better adjuvant than QS-21. The use of the rabbit model may help further our understanding of the critical rotavirus proteins needed to induce active protection. VLPs are a promising candidate for a parenterally administered subunit rotavirus vaccine. PMID:9765471

Study on phototherapeutic keratotomy for bacterial corneal lesions in rabbit

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Xin Zhou

2018-05-01

Full Text Available AIM: To study the effect of phototherapeutic keratectomy(PTKon rabbit bacterial corneal ulcer model and explore the clinical potential of this method. METHODS: Totally 48 eyes from all the 24 New Zealand rabbits were inoculated with Staphylococcus aureus and bacterial corneal ulcer model was established successfully. At 1d after inoculation, 48 eyes were given levofloxacin eye drops when corneal ulcer was confirmed. Then slit lamp inspection and optical coherence tomography(OCTwere performed to measure the central corneal ulcer depth. All the rabbits right eyes were treated with PTK, as an observation group, left eyes were not treated as a control group. The eye section were observed by slit lamp and central thickness of corneal ulcer was measured by OCT at 3 and 7d after this operation. Rabbits were sacrificed and the cornea was removed for pathological section 7d later. RESULTS: The corneal ulcers in both groups had a tendency to heal, showing a decrease in ulcer area and smoothness of the surface. There was no significant difference in the depth of corneal ulcer between the observation group and the control group before PTK(t=0.706, P=0.484. The difference between the two groups of eyes at 3 and 7d after PTK was obviously(PCONCLUSION: PTK can effectively cure rabbit Staphylococcus aureus corneal ulcer and promote ulcer wound healing, which may be used for clinical treatment of patients with bacterial corneal lesions.

A novel peptide derived from human apolipoprotein E is an inhibitor of tumor growth and ocular angiogenesis.

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Partha S Bhattacharjee

2011-01-01

Full Text Available Angiogenesis is a hallmark of tumor development and metastasis and now a validated target for cancer treatment. We previously reported that a novel dimer peptide (apoEdp derived from the receptor binding region of human apolipoprotein E (apoE inhibits virus-induced angiogenesis. However, its role in tumor anti-angiogenesis is unknown. This study demonstrates that apoEdp has anti-angiogenic property in vivo through reduction of tumor growth in a mouse model and ocular angiogenesis in a rabbit eye model. Our in vitro studies show that apoEdp inhibits human umbilical vein endothelial cell proliferation, migration, invasion and capillary tube formation. We document that apoEdp inhibits vascular endothelial growth factor-induced Flk-1 activation as well as downstream signaling pathways that involve c-Src, Akt, eNOS, FAK, and ERK1/2. These in vitro data suggest potential sites of the apoE dipeptide inhibition that could occur in vivo.This is the first evidence that a synthetic dimer peptide mimicking human apoE has anti-angiogenesis functions and could be an anti-tumor drug candidate.

Augmented reality in a tumor resection model.

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Chauvet, Pauline; Collins, Toby; Debize, Clement; Novais-Gameiro, Lorraine; Pereira, Bruno; Bartoli, Adrien; Canis, Michel; Bourdel, Nicolas

2018-03-01

Augmented Reality (AR) guidance is a technology that allows a surgeon to see sub-surface structures, by overlaying pre-operative imaging data on a live laparoscopic video. Our objectives were to evaluate a state-of-the-art AR guidance system in a tumor surgical resection model, comparing the accuracy of the resection with and without the system. Our system has three phases. Phase 1: using the MRI images, the kidney's and pseudotumor's surfaces are segmented to construct a 3D model. Phase 2: the intra-operative 3D model of the kidney is computed. Phase 3: the pre-operative and intra-operative models are registered, and the laparoscopic view is augmented with the pre-operative data. We performed a prospective experimental study on ex vivo porcine kidneys. Alginate was injected into the parenchyma to create pseudotumors measuring 4-10 mm. The kidneys were then analyzed by MRI. Next, the kidneys were placed into pelvictrainers, and the pseudotumors were laparoscopically resected. The AR guidance system allows the surgeon to see tumors and margins using classical laparoscopic instruments, and a classical screen. The resection margins were measured microscopically to evaluate the accuracy of resection. Ninety tumors were segmented: 28 were used to optimize the AR software, and 62 were used to randomly compare surgical resection: 29 tumors were resected using AR and 33 without AR. The analysis of our pathological results showed 4 failures (tumor with positive margins) (13.8%) in the AR group, and 10 (30.3%) in the Non-AR group. There was no complete miss in the AR group, while there were 4 complete misses in the non-AR group. In total, 14 (42.4%) tumors were completely missed or had a positive margin in the non-AR group. Our AR system enhances the accuracy of surgical resection, particularly for small tumors. Crucial information such as resection margins and vascularization could also be displayed.

Effect of hypothyroidism on the purinergic responses of corpus cavernosal smooth muscle in rabbits.

Science.gov (United States)

Yildirim, M K; Bagcivan, I; Sarac, B; Kilicarslan, H; Yildirim, S; Kaya, T

2008-01-01

Several studies have reported evidence of hormonal abnormalities in 25-35% of impotent men. Hypothyroidism has been reported to occur in 6% of impotent men. In the present study, we examined purinergic relaxation responses in hypothyroidism in an experimental rabbit model and compared them with controls to evaluate the possible involvement of the purinergic pathway. The study comprised 20 male New Zealand white rabbits. The rabbits were divided into two equal groups. We tested the effects of ATP, alpha beta ATP, and adenosine precontracted with phenylephrine on the isolated corpus cavernosum preparations from control and hypothyroid rabbits. We also evaluated the effects of ATP, alpha beta ATP, and adenosine on the cGMP levels in the isolated corpus cavernosum preparations from control and hypothyroid rabbits. T3, T4, and testosterone levels were significantly lower in hypothyroid rabbits. ATP, alpha beta ATP, carbachol, and electrical field stimulation (EFS)-induced frequency-dependent relaxation responses in the isolated rabbit corpus cavernosum strips precontracted with phenylephrine reduced significantly (Phypothyroid rabbits. Reduction of relaxation response in hypothyroid rabbits corpus cavernosum can depend on a decreased release of nitric oxide (NO) from nitrergic nerves and endothelium.

Chondromalacia induced by patellar subluxation in the rabbit

DEFF Research Database (Denmark)

Møller, B.N.; Møller-Larsen, F.; Frich, Lars Henrik

1989-01-01

A unilateral patellar malalignment was induced in 20 young and 20 mature rabbits by lateral displacement of the tibial tuberosity, the other knee serving as osteotomized in situ control. At 6 weeks, all the knees appeared macroscopically normal, but histologically definite cartilage degeneration...... was found on the experimental side. At 3 months, macroscopic changes occurred in 5 of 10 mature rabbits, and histologic cartilage degeneration was found in all the experimental knees, most pronounced in mature animals, and particularly in joint facets submitted to high pressure. This experimental model...

Detection and localization of rabbit hepatitis e virus and antigen in systemic tissues from experimentally intraperitoneally infected rabbits.

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Jingjing Mao

Full Text Available Rabbit hepatitis E virus (HEV is a novel genotype of HEV, and is considered to pose a risk of zoonotic transmission. Research into the systemic distribution of rabbit HEV in rabbits during different periods of infection has rarely been reported. To better understand this virus, we infected rabbits with second-passage rabbit HEV via an intraperitoneal route. After inoculation, the infection showed two types, temporary and constant infection. The detection of HEV RNA in the feces varied with time, and serum antigen correlated with fecal HEV RNA. Viremia only appeared 72 days after inoculation. The rabbits remained antibody negative throughout the experimental period. When HEV was localized, several organs besides the liver were HEV RNA positive. Tissue antigen was observed immunohistochemically in the different cells of various organs, especially in parts of the small intestine and the characteristic rabbit gut-associated lymphoid tissue. These data provide valuable information for future research into the pathogenesis of HEV.

Kazakh therapy on differential protein expression of Achilles tendon healing in a 7-day postoperative rabbit model.

Science.gov (United States)

Nuerai, Shawutali; Ainuer, Jialili; Jiasharete, Jielile; Darebai, Redati; Kayrat, Aldyarhan; Tang, Bin; Jiangannur, Zheyiken; Bai, Jingping; Makabel, Bolat

2011-12-01

To compare the effect of cast immobilization with that of early Kiymil arkili emdew (Kazakh exercise therapy) on the post-operative healing of Achilles tendon rupture in rabbits, and to observe the influence of early Kiymil arkili emdew on the differentially expressed proteins in the healing tendon. Forty-five New Zealand white rabbits were randomly divided into three groups (Arm A: control group; Arm B: postoperative immobilization group; and Arm C: postoperative early Kiymil arkili emdew group). After tenotomy, the rabbits of the two experimental groups received microsurgery to repair the ruptured tendons, and then received either cast immobilization or early Kiymil arkili emdew treatment. Achilles tendon tissue samples were collected 7 days after the surgery, and two-dimensional gel electrophoresis and MALDI-TOF-MS technique were used to analyze differentially expressed proteins in the tendon tissue of the three Arms. A total of 462.67 +/- 11.59, 532.33 +/- 27.79, and 515.33 +/- 6.56 protein spots were detected by the two-dimensional polyacrylamide gels in the Achilles tendon samples of the rabbits in Arms A, B, and C, respectively. Nineteen differentially expressed protein spots were randomly selected from Arm C. Among them, 7 were unique, and 15 had five times higher abundance than those in Arm B. These included annexin A2, gelsolin isoforms and alpha-1 Type III collagen. It was confirmed by western blot that gelsolin isoform b, annexin A2, etc. had specific and incremental expression in Arm C. The self-protective instincts of humans were overlooked in the classical postoperative treatment for Achilles tendon rupture with cast immobilization. Kiymil arkili emdew induced the specific and incremental expression of proteins in the repaired Achilles tendon in the early healing stage in a rabbit model, compared with those treated with postoperative cast immobilization. These differentially expressed proteins may contribute to the healing of the Achilles tendon via

Myxoma virus expressing human interleukin-12 does not induce myxomatosis in European rabbits.

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Stanford, Marianne M; Barrett, John W; Gilbert, Philippe-Alexandre; Bankert, Richard; McFadden, Grant

2007-11-01

Myxoma virus (MV) is a candidate for oncolytic virotherapy due to its ability to selectively infect and kill tumor cells, yet MV is a species-specific pathogen that causes disease only in European rabbits. To assess the ability of MV to deliver cytokines to tumors, we created an MV (vMyxIL-12) that expresses human interleukin-12 (IL-12). vMyxIL-12 replicates similarly to wild-type MV, and virus-infected cells secrete bioactive IL-12. Yet, vMyxIL-12 does not cause myxomatosis, despite expressing the complete repertoire of MV proteins. Thus, vMyxIL-12 exhibits promise as an oncolytic candidate and is safe in all known vertebrate hosts, including lagomorphs.

Scintigraphic imaging with 99mTc- exorphin C in rabbits

International Nuclear Information System (INIS)

Ertay, T.; Uenak, P.; Tasci, C.; Zihnioglu, F.; Durak, H.

2005-01-01

Exorphin C is a peptide with five amino acids [(Tyr-Pro-Ile-Ser-Leu) Trifluoroacetate salt] (Sigma) that has an affinity to opioid receptor-expressing tissues and tumors. Exorphin-C was labeled with 99m Tc using glucoheptonate (GH) as bifunctional chelating agent. Then, we investigated its radiopharmaceutical potential as opioid receptor-expressing tissue on rabbits. Quality controls were performed by ITLC, paper electrophoresis and HPLC. Labeling efficiency was higher than 98%. The compound was stable for at least 5 h at room temperature. Scintigraphic imaging with 99m Tc-GH-exorphin C ( 99m Tc-GE) was performed on male Albino rabbits. Static images were obtained from anterior projection using a Camstar XR/T gamma camera at several time intervals. Although a significant amount of activity was seen in the brain, less activity was seen on receptor saturation studies at 30 min. Slight hepatobiliary excretion was seen, though the main excretion route was renal. After saturating, the receptor hepatobiliary excretion was not seen; the only excretion route was renal

Rabbit haemorrhagic disease: are Australian rabbits (Oryctolagus cuniculus) evolving resistance to infection with Czech CAPM 351 RHDV?

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Elsworth, P G; Kovaliski, J; Cooke, B D

2012-11-01

Rabbit haemorrhagic disease is a major tool for the management of introduced, wild rabbits in Australia. However, new evidence suggests that rabbits may be developing resistance to the disease. Rabbits sourced from wild populations in central and southeastern Australia, and domestic rabbits for comparison, were experimentally challenged with a low 60 ID50 oral dose of commercially available Czech CAPM 351 virus - the original strain released in Australia. Levels of resistance to infection were generally higher than for unselected domestic rabbits and also differed (0-73% infection rates) between wild populations. Resistance was lower in populations from cooler, wetter regions and also low in arid regions with the highest resistance seen within zones of moderate rainfall. These findings suggest the external influences of non-pathogenic calicivirus in cooler, wetter areas and poor recruitment in arid populations may influence the development rate of resistance in Australia.

Gadolinium-DTPA enhancement of VX-2 carcinoma of the rabbit kidney on Tl weighted magnetic resonance images

International Nuclear Information System (INIS)

Yancey, J.M.; Ackerman, N.; Kaude, J.V.; Googe, R.E.; Fitzsimmons, J.R.; Scott, K.N.; Mancuso, A.A.; Hackett, R.L.; Hager, D.A.; Caballero, S.; Florida Univ., Gainesville

1987-01-01

Experimental renal carcinoma was induced by percutaneous injection of VX-2 carcinoma cells into the left kidney in New Zealand white rabbits. Magnetic resonance imaging (MRI) was performed at 0.15 T before and after intravenous injection of 0.3 mmol gadolinium-DTPA (Gd-DTPA) per kg body weight. Gd-DTPA enhanced the tumors by increasing the signal intensity on T1 weighted images. The enhancement was evident immediately after Gd-DTPA injection, increasing during the observation time of 30 minutes. Histologically the areas of enhancement corresponded well to the viable tumor tissue. (orig.)

Anti-inflammatory effect of Heliotropium indicum Linn on lipopolysaccharide-induced uveitis in New Zealand white rabbits

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Samuel Kyei

2016-04-01

Full Text Available AIM: To investigate the anti-inflammatory effect of an aqueous whole plant extract of Heliotropium indicum (HIE on endotoxin-induced uveitis in New Zealand white rabbits. METHODS: Clinical signs of uveitis including flares, iris hyperemia and miosis, were sought for and scored in 1.0 mg/kg lipopolysaccharide (LPS -induced uveitic rabbits treated orally with HIE (30-300 mg/kg, prednisolone (30 mg/kg, or normal saline (10 mL/kg. The number of polymorphonuclear neutrophils infiltrating, the protein concentration, as well as levels of tumor necrosis factor-α (TNF-α, prostaglandin E2 (PGE2, and monocyte chemmoattrant protein-1 (MCP-1 in the aqueous humor after the various treatments were also determined. A histopathological study of the anterior uveal was performed. RESULTS: The extract and prednisolone-treatment significantly reduced (P≤0.001 both the clinical scores of inflammation (1.0-1.8 compared to 4.40±0.40 in the normal saline-treated rabbits and inflammatory cells infiltration. The level of protein, and the concentrations of TNF-α, PGE2 and MCP-1 in the aqueous humor were also significantly reduced (P≤0.001. Histopathological studies showed normal uveal morphology in the HIE and prednisolone-treated rabbits while normal saline-treated rabbits showed marked infiltration of inflammatory cells. CONCLUSION: The HIE exhibits anti-inflammatory effect on LPS-induced uveitis possibly by reducing the production of pro-inflammatory mediators.

Intra-articular decorin influences the fibrosis genetic expression profile in a rabbit model of joint contracture.

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Abdel, M P; Morrey, M E; Barlow, J D; Grill, D E; Kolbert, C P; An, K N; Steinmann, S P; Morrey, B F; Sanchez-Sotelo, J

2014-01-01

The goal of this study was to determine whether intra-articular administration of the potentially anti-fibrotic agent decorin influences the expression of genes involved in the fibrotic cascade, and ultimately leads to less contracture, in an animal model. A total of 18 rabbits underwent an operation on their right knees to form contractures. Six limbs in group 1 received four intra-articular injections of decorin; six limbs in group 2 received four intra-articular injections of bovine serum albumin (BSA) over eight days; six limbs in group 3 received no injections. The contracted limbs of rabbits in group 1 were biomechanically and genetically compared with the contracted limbs of rabbits in groups 2 and 3, with the use of a calibrated joint measuring device and custom microarray, respectively. There was no statistical difference in the flexion contracture angles between those limbs that received intra-articular decorin versus those that received intra-articular BSA (66° vs 69°; p = 0.41). Likewise, there was no statistical difference between those limbs that received intra-articular decorin versus those who had no injection (66° vs 72°; p = 0.27). When compared with BSA, decorin led to a statistically significant increase in the mRNA expression of 12 genes (p Cite this article: Bone Joint Res 2014;3:82-8.

A new synthetic granular calcium phosphate compound induces new bone in a sinus lift rabbit model.

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Trbakovic, Amela; Hedenqvist, Patricia; Mellgren, Torbjörn; Ley, Cecilia; Hilborn, Jöns; Ossipov, Dmitri; Ekman, Stina; Johansson, Carina B; Jensen-Waern, Marianne; Thor, Andreas

2018-03-01

The aim of this study was to investigate if a synthetic granular calcium phosphate compound (CPC) and a composite bisphosphonate-linked hyaluronic acid-calcium phosphate hydrogel (HABP·CaP) induced similar or more amount of bone as bovine mineral in a modified sinus lift rabbit model. Eighteen adult male New Zeeland White rabbits, received randomly one of the two test materials on a random side of the face, and bovine mineral as control on the contralateral side. In a sinus lift, the sinus mucosa was elevated and a titanium mini-implant was placed in the alveolar bone. Augmentation material (CPC, HABP·CaP or bovine bone) was applied in the space around the implant. The rabbits were euthanized three months after surgery and qualitative and histomorphometric evaluation were conducted. Histomorphometric evaluation included three different regions of interest (ROIs) and the bone to implant contact on each installed implant. Qualitative assessment (p = <.05), histomorphometric evaluations (p = < .01), and implant incorporation (p = <.05) showed that CPC and bovine mineral induced similar amount of bone and more than the HABP·CaP hydrogel. CPC induced similar amount of bone as bovine mineral and both materials induced more bone than HABP·CaP hydrogel. The CPC is suggested as a synthetic alternative for augmentations in the maxillofacial area. Copyright © 2017 Elsevier Ltd. All rights reserved.

Rabbit haemorrhagic disease: advantages of cELISA in assessing immunity in wild rabbits (Oryctolagus cuniculus).

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Zheng, Tao; Parkes, John P

2011-12-15

Rabbit haemorrhagic disease (RHD) is an acute fatal disease of domestic and wild European rabbits (Oryctolagus cuniculus) caused by RHD virus (RHDV). Accurate assessment of immunity is of great importance for the conservation and control of wild rabbits. We evaluated a competitive ELISA (cELISA) against isotype ELISAs for assessing the protective immunity against the disease by challenging 50 wild-caught rabbits with a lethal dose of RHDV. Death or survival to the challenge was used as a criterion to determine the performance characteristics of the assay for the assessment of immunity in rabbits. At 1:10 dilution, a serum exhibiting ≥ 25% inhibition (1:10(25)) was regarded as the presence of RHDV-specific antibodies. Eleven of 16 (68.8%) rabbits with antibodies at 1:10(25) (<1:40) died of RHD. When the cut-off was moved from 25% to 50% inhibition (1:10(50)) at 1:10 serum dilution, the assay sensitivity, specificity and accuracy for the protective immunity were improved from 84%, 54.2% and 69.4% to 84%, 100% and 91.8%, respectively. We also demonstrated at the epitope amino acid sequence level why the presence of the RHDV-cross reactive benign rabbit calicivirus, which interfered with isotype ELISAs, had little impact on the specificity of the cELISA for the diagnosis of RHDV infection. The presence of RHDV-specific antibody at 1:10(50) by the cELISA is a reliable indicator for the protective immunity. In contrast to isotype ELISAs, the cELISA is a valuable specific tool for monitoring the herd immunity to RHD for the conservation and management of wild rabbits in the field. Copyright © 2011 Elsevier B.V. All rights reserved.

An overview on development and application of an experimental platform for quantitative cardiac imaging research in rabbit models of myocardial infarction.

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Feng, Yuanbo; Bogaert, Jan; Oyen, Raymond; Ni, Yicheng

2014-10-01

To exploit the advantages of using rabbits for cardiac imaging research and to tackle the technical obstacles, efforts have been made under the framework of a doctoral research program. In this overview article, by cross-referencing the current literature, we summarize how we have developed a preclinical cardiac research platform based on modified models of reperfused myocardial infarction (MI) in rabbits; how the in vivo manifestations of cardiac imaging could be closely matched with those ex vivo macro- and microscopic findings; how these imaging outcomes could be quantitatively analyzed, validated and demonstrated; and how we could apply this cardiac imaging platform to provide possible solutions to certain lingering diagnostic and therapeutic problems in experimental cardiology. In particular, tissue components in acute cardiac ischemia have been stratified and characterized, post-infarct lipomatous metaplasia (LM) as a common but hardly illuminated clinical pathology has been identified in rabbit models, and a necrosis avid tracer as well as an anti-ischemic drug have been successfully assessed for their potential utilities in clinical cardiology. These outcomes may interest the researchers in the related fields and help strengthen translational research in cardiovascular diseases.

Autogenous bone particle/titanium fiber composites for bone regeneration in a rabbit radius critical-size defect model.

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Xie, Huanxin; Ji, Ye; Tian, Qi; Wang, Xintao; Zhang, Nan; Zhang, Yicai; Xu, Jun; Wang, Nanxiang; Yan, Jinglong

2017-11-01

To explore the effects of autogenous bone particle/titanium fiber composites on repairing segmental bone defects in rabbits. A model of bilateral radial bone defect was established in 36 New Zealand white rabbits which were randomly divided into 3 groups according to filling materials used for bilaterally defect treatment: in group C, 9 animal bone defect areas were prepared into simple bilateral radius bone defect (empty sham) as the control group; 27 rabbits were used in groups ABP and ABP-Ti. In group ABP, left defects were simply implanted with autogenous bone particles; meanwhile, group ABP-Ti animals had right defects implanted with autogenous bone particle/titanium fiber composites. Animals were sacrificed at 4, 8, and 12 weeks, respectively, after operation. Micro-CT showed that group C could not complete bone regeneration. Bone volume to tissue volume values in group ABP-Ti were better than group ABP. From histology and histomorphometry Groups ABP and ABP-Ti achieved bone repair, the bone formation of group ABP-Ti was better. The mechanical strength of group ABP-Ti was superior to that of other groups. These results confirmed the effectiveness of autologous bone particle/titanium fiber composites for promoting bone regeneration and mechanical strength.