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Sample records for experimental rabbit atherosclerotic

  1. Lipidome of Atherosclerotic Plaques from Hypercholesterolemic Rabbits

    PubMed Central

    Bojic, Lazar A.; McLaren, David G.; Shah, Vinit; Previs, Stephen F.; Johns, Douglas G.; Castro-Perez, Jose M.

    2014-01-01

    The cellular, macromolecular and neutral lipid composition of the atherosclerotic plaque has been extensively characterized. However, a comprehensive lipidomic analysis of the major lipid classes within atherosclerotic lesions has not been reported. The objective of this study was to produce a detailed framework of the lipids that comprise the atherosclerotic lesion of a widely used pre-clinical model of plaque progression. Male New Zealand White rabbits were administered regular chow supplemented with 0.5% cholesterol (HC) for 12 weeks to induce hypercholesterolemia and atherosclerosis. Our lipidomic analyses of plaques isolated from rabbits fed the HC diet, using ultra-performance liquid chromatography (UPLC) and high-resolution mass spectrometry, detected most of the major lipid classes including: Cholesteryl esters, triacylglycerols, phosphatidylcholines, sphingomyelins, diacylglycerols, fatty acids, phosphatidylserines, lysophosphatidylcholines, ceramides, phosphatidylglycerols, phosphatidylinositols and phosphatidylethanolamines. Given that cholesteryl esters, triacylglycerols and phosphatidylcholines comprise greater than 75% of total plasma lipids, we directed particular attention towards the qualitative and quantitative assessment of the fatty acid composition of these lipids. We additionally found that sphingomyelins were relatively abundant lipid class within lesions, and compared the abundance of sphingomyelins to their precursor phosphatidylcholines. The studies presented here are the first approach to a comprehensive characterization of the atherosclerotic plaque lipidome. PMID:25517033

  2. Lipidome of atherosclerotic plaques from hypercholesterolemic rabbits.

    PubMed

    Bojic, Lazar A; McLaren, David G; Shah, Vinit; Previs, Stephen F; Johns, Douglas G; Castro-Perez, Jose M

    2014-12-15

    The cellular, macromolecular and neutral lipid composition of the atherosclerotic plaque has been extensively characterized. However, a comprehensive lipidomic analysis of the major lipid classes within atherosclerotic lesions has not been reported. The objective of this study was to produce a detailed framework of the lipids that comprise the atherosclerotic lesion of a widely used pre-clinical model of plaque progression. Male New Zealand White rabbits were administered regular chow supplemented with 0.5% cholesterol (HC) for 12 weeks to induce hypercholesterolemia and atherosclerosis. Our lipidomic analyses of plaques isolated from rabbits fed the HC diet, using ultra-performance liquid chromatography (UPLC) and high-resolution mass spectrometry, detected most of the major lipid classes including: Cholesteryl esters, triacylglycerols, phosphatidylcholines, sphingomyelins, diacylglycerols, fatty acids, phosphatidylserines, lysophosphatidylcholines, ceramides, phosphatidylglycerols, phosphatidylinositols and phosphatidylethanolamines. Given that cholesteryl esters, triacylglycerols and phosphatidylcholines comprise greater than 75% of total plasma lipids, we directed particular attention towards the qualitative and quantitative assessment of the fatty acid composition of these lipids. We additionally found that sphingomyelins were relatively abundant lipid class within lesions, and compared the abundance of sphingomyelins to their precursor phosphatidylcholines. The studies presented here are the first approach to a comprehensive characterization of the atherosclerotic plaque lipidome.

  3. Paclitaxel-Coated Balloons: Investigation of Drug Transfer in Healthy and Atherosclerotic Arteries - First Experimental Results in Rabbits at Low Inflation Pressure.

    PubMed

    Stolzenburg, Nicola; Breinl, Janni; Bienek, Stephanie; Jaguszewski, Milosz; Löchel, Melanie; Taupitz, Matthias; Speck, Ulrich; Wagner, Susanne; Schnorr, Jörg

    2016-06-01

    Beyond antiproliferative properties, paclitaxel exhibits anti-inflammatory activity, which might be beneficial in the local treatment of nonocclusive coronary artery disease. Paclitaxel release and tissue concentrations after paclitaxel-coated balloon treatment using different pressures have not been investigated so far. The aim of the study was to investigate in an atherosclerotic rabbit model whether drug transfer from paclitaxel-coated balloons into the vessel wall is affected by the presence of atherosclerotic lesions and to which extent it depends on the inflation pressure used. Paclitaxel-coated balloons (3.5 μg/mm(2) paclitaxel) were inflated with pressures of 1, 2, or 6 atm (60s) in healthy (n = 39) and atherosclerotic (n = 22) arteries of New Zealand White Rabbits. Paclitaxel content in arterial walls (10 min after interventions) and paclitaxel remaining on balloons after treatment were analyzed using high-performance liquid chromatography. Median paclitaxel tissue concentrations were 829.3 μg/g (IQR 636.5-1487 μg/g) in healthy and 375.7 μg/g (IQR 169.8-771.6 μg/g) in atherosclerotic arteries (p = 0.0002). The paclitaxel tissue concentration was dependent on inflation pressure (1 atm vs. 2 atm vs. 6 atm) in atherosclerotic arteries (p = 0.0106) but not in healthy arteries (p ≥ 0.05). Atherosclerotic lesions impede the transfer of paclitaxel into arterial walls. Higher inflation pressures resulted in an increased paclitaxel transfer in atherosclerotic but not in healthy arteries. However, it is assumed that the tissue concentrations achieved with an inflation pressure of 2 atm are potentially effective in this model.

  4. Gingival vascular damage in atherosclerotic rabbits: hydroxytyrosol and squalene benefits.

    PubMed

    Bullon, Pedro; Quiles, Jose L; Morillo, Juan M; Rubini, Corrado; Goteri, Gaia; Granados-Principal, Sergio; Battino, Maurizio; Ramirez-Tortosa, McArmen

    2009-09-01

    Cardiovascular alterations and periodontal disease have been associated, although cardiovascular disease treatments have not yet been tested against periodontal alterations. We investigated effects of squalene, hydroxytyrosol and coenzyme Q(10) on gingival tissues of rabbits fed on an atherosclerotic diet. Forty-eight rabbits were distributed in six groups. Control group was fed on standard chow for 80 days. The rest were fed with an atherogenic diet for 50 days. After that, a group was sacrificed and the rest were subjected for another extra 30 days on commercial chow alone or supplemented with coenzyme Q(10), squalene or hydroxytyrosol. Atherosclerotic rabbits had higher fibrosis and endothelial activation and lower cellularity in gingival mucosa than controls (P<0.05). Hydroxytyrosol reduced endothelial activation (P<0.05) and squalene additionally decreased fibrosis (P<0.05). Results suggest that gingival vascular changes after the atherosclerotic diet have been reversed by hydroxytyrosol and squalene, natural products from the minor fraction of virgin olive oil.

  5. In vivo determination of arterial collagen synthesis in atherosclerotic rabbits

    SciTech Connect

    Opsahl, W.P.; DeLuca, D.J.; Ehrhart, L.A.

    1986-03-01

    Collagen and non-collagen protein synthesis rates were determined in vivo in tissues from rabbits fed a control or atherogenic diet supplemented with 2% peanut oil and 0.25% cholesterol for 4 months. Rabbits received a bolus intravenous injection of L-(/sup 3/H)-proline (1.0 mCi/kg) and unlabeled L-proline (7 mmoles/kg) in 0.9% NaCl. Plasma proline specific activity decreased only 20% over 5 hr and was similar to the specific activity of free proline in tissues. Thoracic aortas from atherosclerotic rabbits exhibited raised plaques covering at least 75% of the surface. Thoracic intima plus a portion of the media (TIM) was separated from the remaining media plus adventitia (TMA). Dry delipidated weight, total collagen content, and collagen as a percent of dry weight were increased significantly in the TIM of atherosclerotic rabbits. Collagen synthesis rates and collagen synthesis as a percent of total protein synthesis were likewise increased both in the TIM and in the abdominal aortas. No differences from controls either in collagen content or collagen synthesis rates were observed in the TMA, lung or skin. These results demonstrate for the first time in vivo that formation of atherosclerotic plaques is associated with increased rates of collagen synthesis. Furthermore, as previously observed with incubations in vitro, collagen synthesis was elevated to a greater extent than noncollagen protein synthesis in atherosclerotic aortas from rabbits fed cholesterol plus peanut oil.

  6. Cryotherapy increases features of plaque stability in atherosclerotic rabbits.

    PubMed

    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.

  7. Photodynamic diagnostic in atherosclerotic artery wall of rabbits

    NASA Astrophysics Data System (ADS)

    Corbani, Elaine A.; Rodrigues, Katia C.; Hage, Raduan; Duarte, Janaina; Silveira, Landulfo, Jr.; Villaverde, Antonio G. J. B.; Zangaro, Renato A.; Pacheco, Marcos T. T.

    2001-05-01

    A growing number of studies have demonstrated that autofluorescence and induced fluorescence spectroscopy can be used to distinguish normal and abnormal tissues in vivo. Through photochemical accumulation in atherosclerotic lesions it is possible to obtain induced fluorescence, this accumulation has been demonstrated in many researches. The aim of this study was to diagnose, by aluminum phthalocyanine transadventitial fluorescence, atherosclerotic plaques in artery wall of rabbits. Five male Norfolk rabbits were submitted to a high level cholesterol diet for 9 weeks. When the blood cholesterol level reached around 1000 mg/dl three of these animals were injected intravenously 50(M/50(l of aluminum phthalocyanine (AlPc). After 24 hours these animals were submitted to a surgery to expose the iliac artery. The transadventitial fluorescence spectra were acquired in several points over the artery. Characteristic peaks of the collagen, the porphyrin and the induced by AlPc were observed.

  8. Inadequate dietary magnesium intake increases atherosclerotic plaque development in rabbits

    PubMed Central

    King, Jennifer L.; Miller, Rita J.; Blue, James P.; O'Brien, William D.; Erdman, John W.

    2012-01-01

    Epidemiological studies have shown dietary magnesium (Mg) intake and serum Mg levels to be inversely correlated with the development of atherosclerosis. We hypothesized that low levels of Mg would promote atherosclerotic plaque development in rabbits. New Zealand white rabbits (4 months old, n = 22) were fed an atherogenic diet containing 0.12% (−Mg), 0.27% (control), or 0.43% (+Mg) Mg for 8 weeks. Blood samples were obtained at baseline, 2, 4, 6, and 8 weeks and were assayed for total cholesterol, high-density lipoprotein (HDL), non-HDL, triglycerides (TG), C-reactive protein, serum Mg, and erythrocyte Mg. Aortas from −Mg had significantly more plaque, with an intima thickness 42% greater than control and 36% greater than +Mg. Serum cholesterol levels rose over time, and at 8 weeks, −Mg had the highest and +Mg the lowest total and non-HDL cholesterol and TG levels, although these results did not reach significance. Over time, serum Mg levels increased, and erythrocyte Mg levels decreased. C-reactive protein significantly increased in all groups at 4 and 6 weeks but returned to baseline levels by 8 weeks. This study supports the hypothesis that inadequate intake of Mg results in an increase in atherosclerotic plaque development in rabbits. PMID:19555816

  9. Effect of Si-Miao-Yong-An on the stability of atherosclerotic plaque in a diet-induced rabbit model.

    PubMed

    Peng, Li; Li, Ming; Xu, Ying-Zhi; Zhang, Guang-Yin; Yang, Cui; Zhou, Ya-Nan; Li, Liang-Jun; Zhang, Jun-Ping

    2012-08-30

    Si-Miao-Yong-An (Trade name: Mai-Luo-Ning), a Chinese herbal formulation comprising Flos Lonicerae Japonicae, Radix Scrophulariae Ningpoensis, Radix Angelicae Sinensis and Radix Glycyrrhizae Uralensis, has been used in treating ischemic cardiovascular and cerebrovascular diseases for many years. Clinical and experimental studies have shown that Si-Miao-Yong-An can inhibit the inflammatory response and antagonize the blood clotting process. To investigate the effect of Si-Miao-Yong-An on atherosclerotic plaque stability in rabbit model. Seventy male rabbits were divided into four groups. Rabbits in the normal group were fed with normal diet, while rabbits in model group and drug treatment groups were fed with high cholesterol diet, underwent BSA-induced immunologic injury and balloon-induced mechanical injury. After atherosclerotic rabbits were treated with simvastatin or Si-Miao-Yong-An for 16 weeks, blood and aorta in four groups were collected for analysis. Si-Miao-Yong-An reduced the level of triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) in blood after treatment for 16 weeks. Compared with model group, Si-Miao-Yong-An decreased the content of many inflammatory cytokines in blood and plaque. Morphological analysis of abdominal aorta showed that Si-Miao-Yong-An increased fibrous cap thickness and smooth muscle cells, reduced lipid core area and macrophages, and contributed to inhibit matrix degradation and inflammatory response. In this study, we provided evidence for that Si-Miao-Yong-An could promote the stability of atherosclerotic plaque in the rabbit model, indicating that this medicine was a reasonable drug treating cardiovascular diseases in clinical. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  10. Regulation of cellular proliferation and intimal formation following balloon injury in atherosclerotic rabbit arteries.

    PubMed Central

    Simari, R D; San, H; Rekhter, M; Ohno, T; Gordon, D; Nabel, G J; Nabel, E G

    1996-01-01

    Injury to atherosclerotic arteries induces the expression of growth regulatory genes that stimulate cellular proliferation and intimal formation. Intimal expansion has been reduced in vivo in nonatherosclerotic balloon-injured arteries by transfer of genes that inhibit cell proliferation. It is not known, however, whether vascular cell proliferation can be inhibited after injury in more extensively diseased atherosclerotic arteries. Accordingly, the purpose of this study was to investigate whether expression of recombinant genes in atherosclerotic arteries after balloon injury could inhibit intimal cell proliferation. To test this hypothesis, we examined the response to balloon injury in atherosclerotic rabbit arteries after gene transfer of herpesvirus thymidine kinase gene (tk) and administration of ganciclovir. Smooth muscle cells from hyperlipidemic rabbit arteries infected with adenoviral vectors encoding tk were sensitive to ganciclovir, and bystander killing was observed in vitro. In atherosclerotic arteries, a human placental alkaline phosphatase reporter gene was expressed in intimal and medial smooth muscle cells and macrophages, identifying these cells as targets for gene transfer. Expression of tk in balloon-injured hyperlipidemic rabbit arteries followed by ganciclovir treatment resulted in a 64% reduction in intimal cell proliferation 7 d after gene transfer (P = 0.004), and a 35-49% reduction in internal area 21 d after gene transfer, compared with five different control groups (P < 0.05). Replication of smooth muscle cells and macrophages was inhibited by tk expression and ganciclovir treatment. These findings indicate that transfer of a gene that inhibits cellular proliferation limits the intimal area in balloon-injured atherosclerotic arteries. Molecular approaches to the inhibition of cell proliferation in atherosclerotic arteries constitute a possible treatment for vascular proliferative diseases. PMID:8690797

  11. Increased expression of heat shock protein 65 coincides with a population of infiltrating T lymphocytes in atherosclerotic lesions of rabbits specifically responding to heat shock protein 65.

    PubMed Central

    Xu, Q; Kleindienst, R; Waitz, W; Dietrich, H; Wick, G

    1993-01-01

    We have shown previously that atherosclerotic lesions can be induced in normocholesterolemic rabbits by immunization with mycobacterial heat shock protein 65 (hsp65), which has a high degree of sequence homology with mammalian hsp60. To investigate a possible relationship between hsp60 expression and the antigenic specificities of infiltrating T cells in the lesion, 38 New Zealand White rabbits were treated either by immunization with recombinant mycobacterial hsp65 or by administration of a 0.2% cholesterol diet. Atherosclerotic lesions were observed after 16 wk, particularly in the aortic arch and arterial bifurcations of rabbits immunized with hsp65 or fed with a cholesterol-rich diet. Hsp65 staining of aortas showed a heterogeneous distribution, and significantly increased staining intensity in atherosclerotic lesions compared to aortic media or adventitia. This abundantly expressed hsp65 was observed in atherosclerotic lesions induced by hsp65 immunization as well as those induced by cholesterol-rich diet alone. Interestingly, a population of the T lymphocytes isolated from all forms of atherosclerotic lesions specifically responded to hsp65 in vitro. IL-2-expanded T cell lines derived from atherosclerotic lesions showed a significantly higher hsp65 reactivity than those developed from peripheral blood of the same donor. Furthermore, levels of circulating antibodies and numbers of spleen cells specifically reacting against hsp65 were elevated in all experimental animals. Flow cytometric analysis of spleen cells showed elevated immune response-associated antigen expression in treated animals. In conclusion, increased hsp65 expression in intimal cells and the presence of hsp65-specific T cells in blood and in atherosclerotic lesions may be important in initiating the development of atherosclerosis and perpetuating the lesions. Images PMID:8514876

  12. Overexpression of ABCG1 protein attenuates arteriosclerosis and endothelial dysfunction in atherosclerotic rabbits

    PubMed Central

    Münch, Götz; Bültmann, Andreas; Li, Zhongmin; Holthoff, Hans-Peter; Ullrich, Julia; Wagner, Silvia; Ungerer, Martin

    2012-01-01

    The ABCG1 protein is centrally involved in reverse cholesterol transport from the vessel wall. Investigation of the effects of ABCG1 overexpression or knockdown in vivo has produced controversial results and strongly depended on the gene intervention model in which it was studied. Therefore, we investigated the effect of local overexpression of human ABCG1 in a novel model of vessel wall-directed adenoviral gene transfer in atherosclerotic rabbits. We conducted local, vascular-specific gene transfer by adenoviral delivery of human ABCG1 (Ad-ABCG1-GFP) in cholesterol-fed atherosclerotic rabbits in vivo. Endothelial overexpression of ABCG1 markedly reduced atheroprogression (plaque size) and almost blunted vascular inflammation, as shown by markedly reduced macrophage and smooth muscle cell invasion into the vascular wall. Also endothelial function, as determined by vascular ultrasound in vivo, was improved in rabbits after gene transfer with Ad-ABCG1-GFP. Therefore, both earlier and later stages of atherosclerosis were improved in this model of somatic gene transfer into the vessel wall. In contrast to results in transgenic mice, over-expression of ABCG1 by somatic gene transfer to the atherosclerotic vessel wall results in a significant improvement of plaque morphology and composition, and of vascular function in vivo. PMID:23185679

  13. Increased activity of guanylate cyclase in the atherosclerotic rabbit aorta: role of non-endothelial nitric oxide synthases.

    PubMed Central

    Rupin, A.; Behr, D.; Verbeuren, T. J.

    1996-01-01

    1. Experiments were performed to examine the effects of putative non-endothelial nitric oxide on the soluble guanylate cyclase activity of severe atherosclerotic aortae from hypercholesterolaemic rabbits fed a cholesterol rich diet for 45 weeks. 2. The guanosine 3':5'-cyclic monophosphate (cyclic GMP) content of aortae from rabbits fed either a control diet or a diet containing 0.3% cholesterol for 45 weeks was quantified in saline extracts or in trichloracetic acid/either extracts by use of a competitive immunoenzymatic assay. Rabbit anti-cyclic GMP immunoglobulin G was covalently linked to the solid phase, in order to avoid false positive results due to high rabbit immunoglobulin G concentrations in the atherosclerotic saline extracts. 3. Saline extracts of atherosclerotic aortae which were harvested immediately after death (intact aortae) contained about 6 fold more cyclic GMP than control aortae when expressed in pmol cyclic GMP mg-1 protein. The cyclic GMP concentrations in trichloracetic acid/ether extracts of atherosclerotic and control aortae expressed in pmol mg-1 fresh tissue were not significantly different. 4. Neointimal-medial explants from atherosclerotic and control aortae were placed in a physiological saline solution and incubated at 37 degrees C for six hours in an incubator gassed with 5% CO2. Before the incubation, the cyclic GMP concentrations in saline extracts of atherosclerotic explants (0.74 +/- 0.27 pmol mg-1) were found to be 17 fold higher than those of control explants (0.043 +/- 0.008 pmol mg-1). The cyclic GMP content of control explants decreased significantly after 6 h of incubation, while that of atherosclerotic explants remained elevated. 5. Chronic administration of NG-nitro-L-arginine methyl ester, a non selective inhibitor of nitric oxide synthases, at 12 mg kg-1 day-1 subcutaneously for one month did not reduce the cyclic GMP concentration of intact atherosclerotic aortae, while that of intact aortae from control rabbits

  14. Selepressin and Arginine Vasopressin Do Not Display Cardiovascular Risk in Atherosclerotic Rabbit

    PubMed Central

    Boucheix, Olivier; Blakytny, Robert; Haroutunian, Gerard; Henriksson, Marie; Laporte, Regent; Milano, Stephane; Reinheimer, Torsten M.

    2016-01-01

    Background Septic shock remains associated with significant mortality rates. Arginine vasopressin (AVP) and analogs with V1A receptor agonist activity are increasingly used to treat fluid-resistant vasodilatory hypotension, including catecholamine-refractory septic shock. Clinical studies have been restricted to healthy volunteers and catecholamine-refractory septic shock patients excluding subjects with cardiac co-morbidities because of presumed safety issues. The novel selective V1A receptor agonist selepressin, with short half-life, has been designed to avoid V2 receptor-related complications and long-term V1A receptor activation. Cardiovascular safety of selepressin, AVP, and the septic shock standard of care norepinephrine was investigated in a rabbit model of early-stage atherosclerosis. Methods Atherosclerosis was established in New Zealand White rabbits using a 1% cholesterol-containing diet. Selepressin, AVP, or norepinephrine was administered as cumulative intravenous infusion rates to atherosclerotic and non-atherosclerotic animals. Results Selepressin and AVP induced a slight dose-dependent increase in arterial pressure (AP) associated with a moderate decrease in heart rate, no change in stroke volume, and a moderate decrease in aortic blood flow (ABF). In contrast, norepinephrine induced a marked dose-dependent increase in AP associated with a lesser decrease in the heart rate, an increase in stroke volume, and a moderate increase in ABF. For all three vasopressors, there was no difference in responses between atherosclerotic and non-atherosclerotic animals. Conclusion Further studies should be considered using more advanced atherosclerosis models, including with septic shock, before considering septic shock clinical trials of patients with comorbidities. Here, selepressin and AVP treatments did not display relevant cardiovascular risk in early-stage rabbit atherosclerosis. PMID:27788216

  15. Regression of atherosclerotic lesions by high density lipoprotein plasma fraction in the cholesterol-fed rabbit.

    PubMed

    Badimon, J J; Badimon, L; Fuster, V

    1990-04-01

    The effects of homologous plasma HDL and VHDL fractions on established atherosclerotic lesions were studied in cholesterol-fed rabbits. Atherosclerosis was induced by feeding the animals a 0.5% cholesterol-rich diet for 60 d (group 1). Another group of animals were maintained on the same diet for 90 d (group 2). A third group was also fed the same diet for 90 d but received 50 mg HDL-VHDL protein per wk (isolated from normolipemic rabbit plasma) during the last 30 d (group 3). Aortic atherosclerotic involvement at the completion of the study was 34 +/- 4% in group 1, 38.8 +/- 5% in group 2, and 17.8 +/- 4% in group 3 (P less than 0.005). Aortic lipid deposition was also significantly reduced in group 3 compared with group 1 (studied at only 60 d) and group 2. This is the first in vivo, prospective evidence of the antiatherogenic effect of HDL-VHDL against preexisting atherosclerosis. Our results showed that HDL plasma fractions were able to induce regression of established aortic fatty streaks and lipid deposits. Our results suggest that it may be possible not only to inhibit progression but even to reduce established atherosclerotic lesions by HDL administration.

  16. MRI study of atherosclerotic plaque progression using ultrasmall superparamagnetic iron oxide in Watanabe heritable hyperlipidemic rabbits.

    PubMed

    Kaneko, C; Nitta, N; Tsuchiya, K; Watanabe, S; Nitta-Seko, A; Ohta, S; Otani, H; Sonoda, A; Murata, K; Shiomi, M

    2015-09-01

    The purpose of this study was to evaluate plaque progression by using MRI with ultrasmall superparamagnetic iron oxide (USPIO) and by histopathological studies. We divided 12 Watanabe heritable hyperlipidemic (WHHL) rabbits into 4 groups based on their age (3, 9, 14 and 26 months) and injected them intravenously with 0.8 mmol (Fe) kg(-1) of USPIO (size, 32 nm; concentration, 15 mg dl(-1)). On the fifth post-injection day, they were again given an intravenous injection with 40 μmol kg(-1) of the same USPIO, and MR angiography (MRA) was performed. The signal-to-noise ratio (SNR) in regions of interest in the wall of the upper abdominal aorta was calculated on coronal images. Specimens from the same level of the aorta were subjected to iron staining and RAM-11 immunostaining and used for histopathological study. For statistical analysis of the MRA and histopathological findings, we used analysis of variance [Tukey's honest significant difference (HSD) test]. In 9-month-old rabbits, the SNR was significantly lower than in rabbits of the other ages (p < 0.01), and the area of RAM-11 (DAKO Corporation, Glostrup, Denmark) and iron uptake in the aortic wall was significantly larger (RAM-11, p < 0.01; iron, p < 0.05). These areas were the smallest in 3-month-old rabbits. Histopathologically, the number of macrophages was the greatest in 9-month-old rabbits. Our findings indicate that the SNR on MRI scans reflects the number of macrophages in the aortic wall of WHHL rabbits. USPIO-enhanced MRI visualized the accumulation of macrophages in early atherosclerotic plaques of WHHL rabbits in the course of natural progression.

  17. Antioxidants attenuate atherosclerotic plaque development in a balloon-denuded and -radiated hypercholesterolemic rabbit

    SciTech Connect

    Leborgne, Laurent; Fournadjiev, Jana; Pakala, Rajbabu; Dilcher, Christian; Cheneau, Edouard; Wolfram, Roswitha; Hellinga, David; Seaborn, Rufus; O'Tio, Fermin; Waksman, Ron

    2003-03-01

    Background: Oxidation of lipoproteins is considered to be a key contributor to atherogenesis. Antioxidants are potential antiatherogenic agents because they can inhibit lipoprotein oxidation. Radiation has been shown to increase oxidative stress leading to increased atherogenesis. This study is designed to test the potential of antioxidants to inhibit atherosclerotic plaque progression in balloon-denuded and -radiated rabbits. Methods and Results: Two groups of New Zealand white rabbits (n=36) were fed with 1% cholesterol diet (control diet) or with 1% cholesterol diet containing a mixture of various antioxidants for 1 week. Iliac arteries in all the animals were balloon denuded and continued to fed with 0.15% cholesterol diet or 0.15% cholesterol diet containing antioxidants (antioxidant diet). Four weeks after balloon denudation one iliac artery in 12 animals from each group was radiated and all the animals were continued to be fed with the same diet. Four weeks after radiation animals were sacrificed and morphometric analysis of iliac arteries (n=12) in nonradiated and radiated animals were performed. Plaque area (PA) in the rabbits that were fed with cholesterol diet is 0.2{+-}0.12 mm{sup 2}, and it is increased by 2.75-fold (P<.05) in the radiated arteries of animals fed with cholesterol diet. Plaque area in the animals fed with antioxidant diet is 50% less then the one in the animals fed with cholesterol diet. Similarly, plaque area in radiated arteries of the animals fed with antioxidant diet is 50% less then the animals fed with cholesterol diet. Conclusion: Antioxidants significantly attenuate atherosclerotic plaque progression in balloon-injured and -radiated hypercholesterolemic rabbits.

  18. Lipofundin-Induced Hyperlipidemia Promotes Oxidative Stress and Atherosclerotic Lesions in New Zealand White Rabbits

    PubMed Central

    Delgado Roche, Livan; Acosta Medina, Emilio; Fraga Pérez, Ángela; Bécquer Viart, María A.; Soto López, Yosdel; Falcón Cama, Viviana; Vázquez López, Ana M.; Martínez-Sánchez, Gregorio; Fernández-Sánchez, Eduardo

    2012-01-01

    Atherosclerosis represents a major cause of death in the world. It is known that Lipofundin 20% induces atherosclerotic lesions in rabbits, but its effects on serum lipids behaviour and redox environment have not been addressed. In this study, New Zealand rabbits were treated with 2 mL/kg of Lipofundin for 8 days. Then, redox biomarkers and serum lipids were determined spectrophotometrically. On the other hand, the development of atherosclerotic lesions was confirmed by eosin/hematoxylin staining and electron microscopy. At the end of the experiment, total cholesterol, triglycerides, cholesterol-LDL, and cholesterol-HDL levels were significantly increased. Also, a high index of biomolecules damage, a disruption of both enzymatic and nonenzymatic defenses, and a reduction of nitric oxide were observed. Our data demonstrated that Lipofundin 20% induces hyperlipidemia, which promotes an oxidative stress state. Due to the importance of these phenomena as risk factors for atherogenesis, we suggest that Lipofundin induces atherosclerosis mainly through these mechanisms. PMID:21977325

  19. Cervical Rotatory Manipulation Decreases Uniaxial Tensile Properties of Rabbit Atherosclerotic Internal Carotid Artery

    PubMed Central

    Qi, Ji; Zhang, Lei; Chen, Chao; Mondal, Shubhro; Ping, Kaike; Chen, Yili

    2017-01-01

    Objective. To investigate the effects of one of the Chinese massage therapies, cervical rotatory manipulation (CRM), on uniaxial tensile properties of rabbit atherosclerotic internal carotid artery (ICA). Methods. 40 male purebred New Zealand white rabbits were randomly divided into CRM-Model group, Non-CRM-Model group, CRM-Normal group, and Non-CRM-Normal group. After modeling (atherosclerotic model) and intervention (CRM or Non-CRM), uniaxial tensile tests were performed on the ICAs to assess the differences in tensile mechanical properties between the four groups. Results. Both CRM and modeling were the main effects affecting physiological elastic modulus (PEM) of ICA. PEM in CRM-Model group was 1.81 times as much as Non-CRM-Model group, while the value in CRM-Model group was 1.34 times as much as CRM-Normal group. Maximum elastic modulus in CRM-Model group was 1.80 times as much as CRM-Normal group. Max strains in CRM-Model group and Non-CRM-Model group were 30.98% and 28.71% lower than CRM-Normal group and Non-CRM-Normal group, respectively. However, whether treated with CRM or not, the uniaxial tensile properties of healthy ICAs were not statistically different. Conclusion. CRM may decrease the uniaxial tensile properties of rabbit arteriosclerotic ICA, but with no effect on normal group. The study will aid in the meaningful explanation of the controversy about the harmfulness of CRM and the suitable population of CRM. PMID:28303160

  20. Macrophages and smooth muscle cells express lipoprotein lipase in human and rabbit atherosclerotic lesions.

    PubMed Central

    Ylä-Herttuala, S; Lipton, B A; Rosenfeld, M E; Goldberg, I J; Steinberg, D; Witztum, J L

    1991-01-01

    Lipoprotein lipase (LPL; EC 3.1.1.34) may promote atherogenesis by producing remnant lipoproteins on the endothelial surface and by acting on lipoproteins in the artery wall. In vitro, smooth muscle cells and macrophages synthesize LPL, but in human carotid lesions only a few smooth muscle cells were reported to contain LPL protein. Endothelial cells do not synthesize LPL in vitro, but in normal arteries intense immunostaining for LPL is present on the endothelium. We used Northern blot analysis, in situ hybridization, and immunocytochemistry of human and rabbit arteries to determine cellular distribution and the site of the synthesis of LPL in atherosclerotic lesions. Northern blot analysis showed that LPL mRNA was detectable in macrophage-derived foam cells isolated from arterial lesions of "ballooned" cholesterol-fed rabbits. In situ hybridization studies of atherosclerotic lesions with an antisense riboprobe showed a strong hybridization signal for LPL mRNA in some, but not all, lesion macrophages, which were mostly located in the subendothelial and edge areas of the lesions. Also, some smooth muscle cells in lesion areas also expressed LPL mRNA. Immunocytochemistry of frozen sections of rabbit lesions with a monoclonal antibody to human milk LPL showed intense staining for LPL protein in macrophage-rich intimal lesions. The results suggest that lesion macrophages and macrophage-derived foam cells express LPL mRNA and protein. Some smooth muscle cells in the lesion areas also synthesize LPL. These data are consistent with an important role for LPL in atherogenesis. Images PMID:1719546

  1. Tibolone inhibits aortic atherosclerotic lesionformation in oophorectomized cholesterol-fed rabbits

    PubMed Central

    Castelo-Branco, Camil; Sanjuán, Alex; Ascaso, Carles; Colodrón, Marta; Blümel, Juan Enrique; Casals, Elena; Ordi, Jaume; Vanrell, Juan Antonio

    2003-01-01

    BACKGROUND: Tibolone is a synthetic steroid effective for the treatment of climacteric symptoms and osteoporosis. Long term treatment with tibolone is associated with a significant decrease in cholesterol levels due to a parallel decrease in high-density lipoprotein. However, the effect of these changes on atherogenesis is not known. OBJECTIVE: To investigate the effect of tibolone therapy on aorta atherogenesis. MATERIAL AND METHODS: Thirty-two New Zealand white rabbits were fed cholesterol-rich feed and studied for four months. The rabbits underwent laparotomy and were randomly assigned to four groups. Twenty-four rabbits underwent bilateral ovariectomy; of these, eight received tibolone (group T), eight received estradiol valerate (group E), eight received placebo after sterilization (group C), and eight were sham operated (group S). RESULTS: After receiving the cholesterol-rich diet, total levels of cholesterol increased in group C from 3.17±0.72 mmol/L to 35.36±9.01 mmol/L, in group S from 2.88±0.9 mmol/L to 28.76±9.442 mmol/L, in group E from 1.69±0.44 mmol/L to 1.69±0.44 mmol/L and in group T from 2.03±0.22 mmol/L to 26.33±13.45 mmol/L (no significant differences were observed among the groups at the end of the study). At four months, the cholesterol- rich diet caused atherosclerotic lesions in both treated and untreated rabbits, affecting 30.47±12.2%, 24.51±16.1%, 17.91±10.19% and 10.21±6.8% of the aortic surface for groups C, S, E and T, respectively (P<0.01 for treated groups). CONCLUSION: The principal result from this study was that treatment with tibolone in cholesterol-fed ovariectomized rabbits reduces aortic atherosclerotic lesion formation and that this reduction is not related to plasma lipid levels. PMID:19644583

  2. Ultrastructural changes in atherosclerotic plaques following the instillation of airborne particulate matter into the lungs of rabbits

    PubMed Central

    Tranfield, Erin M; van Eeden, Stephan F; Yatera, Kazuhiro; Hogg, James C; Walker, David C

    2010-01-01

    BACKGROUND: Epidemiological studies have established that cardiovascular events account for the greatest number of air pollution-related deaths. However, the underlying structural changes are still unknown. OBJECTIVE: To investigate changes in the ultrastructure of atherosclerotic plaques in Watanabe heritable hyperlipidemic (WHHL) rabbits following the instillation of ambient particulate matter air pollution (particles smaller than 10 μm in diameter) into the lungs. METHODS: WHHL rabbits (n=8) exposed to 5 mg of ambient particles (Environmental Health Centre – 1993 [EHC-93]; suspended in saline and instilled in the airway) twice per week for four weeks were compared with control WHHL rabbits (n=8) treated with saline alone. RESULTS: All abdominal aortic plaques were examined using light and electron microscopy, which showed the following: increased accumulation of macrophage-derived foam cells immediately below the endothelial plaque surface (P=0.04); increased contact between these foam cells and the dense subendothelial extracellular matrix (P<0.005) with reduction (P<0.0001) and fragmentation (P<0.0001) of this matrix; and emigration of macrophage-derived foam cells from the plaques in exposed rabbits. In addition, immunohistochemistry verified the presence of type IV collagen in the thickened extracellular matrix material subtending the endothelium. CONCLUSIONS: The ultrastructure of atherosclerotic plaques in EHC-93-instilled rabbits differed from the ultrastructure observed in rabbits that did not receive EHC-93. These ultrastructural differences are consistent with greater endothelial instability in the plaques of atherosclerosis-prone rabbits. PMID:20847974

  3. [Effect of vitamin E on myosin light chain kinase activity and endothelial permeability of the artery in atherosclerotic rabbit].

    PubMed

    Zhu, Hua-qing; Ren, Bin; Xiong, Jiang-xia; Hu, Ruo-lei; Liu, Xiao-ying; Wang, Xue; Zhang, Su-mei; Liu, Hui-lan; Jiang, Zhi-kui; Zhou, Qing; Gui, Shu-yu; Wang, Yuan

    2003-08-01

    To study the effect of vitamin E (Vit E) on the myosin light chain kinase(MLCK) activity and the endothelial permeability of the artery in atherosclerotic rabbits. The MLCK activity of rabbit artery was measured by incorporation of gamma-(32)P. The endothelial permeability was accessed by immunofluorescence. The model of atherosclerosis was established after rabbits were fed with cholesterol for four weeks. The activity of MLCK increased markedly, and there was significantly statistical difference compared with the normal control (P<0.05). When the rabbits were fed with cholesterol for twelve weeks or with cholesterol and Vit E for twelve weeks, the activity of MLCK did not change markedly, and there was no statistical difference compared with the normal control, respectively (P>0.05). The permeability of arterial wall was increased after the rabbits were fed with cholesterol for four weeks, and the permeability increased even more obviously after the rabbits were fed with cholesterol for twelve weeks. The permeability appeared to be decreased when Vit E was added into the cholesterol feeding. The change in integrity of arterial wall may be associated with the increase of the activity of MLCK. Vit E may decrease the MLCK activity. Vit E may decrease the endothelial permeability of atherosclerotic rabbits.

  4. Expression of monocyte chemoattractant protein 1 in macrophage-rich areas of human and rabbit atherosclerotic lesions.

    PubMed Central

    Ylä-Herttuala, S; Lipton, B A; Rosenfeld, M E; Särkioja, T; Yoshimura, T; Leonard, E J; Witztum, J L; Steinberg, D

    1991-01-01

    The recruitment of monocyte-macrophages into the artery wall is one of the earliest events in the pathogenesis of atherosclerosis. Monocyte chemoattractant protein 1 (MCP-1) is a potent monocyte chemoattractant secreted by many cells in vitro, including vascular smooth muscle and endothelial cells. To test whether it is expressed in the artery in vivo, we used Northern blot analysis, in situ hybridization, and immunocytochemistry to study the expression of MCP-1 in normal and atherosclerotic human and rabbit arteries. Northern blot analysis showed that MCP-1 mRNA could be isolated from rabbit atherosclerotic lesions but not from the intima media of normal animals. Furthermore, MCP-1 mRNA was extracted from macrophage-derived foam cells isolated from arterial lesions of ballooned cholesterol-fed rabbits, whereas alveolar macrophages isolated simultaneously from the same rabbits did not express MCP-1 mRNA. MCP-1 mRNA was detected by in situ hybridization in macrophage-rich regions of both human and rabbit atherosclerotic lesions. No MCP-1 mRNA was found in sublesional medial smooth muscle cells or in normal arteries. By using immunocytochemistry, MCP-1 protein was demonstrated in human lesions, again only in macrophage-rich regions. Immunostaining of the serial sections with an antiserum against malondialdehyde-modified low density lipoprotein indicated the presence of oxidized low density lipoprotein indicated the presence of oxidized low density lipoprotein and/or other oxidation-specific lipid-protein adducts in the same areas that contained macrophages and MCP-1. We conclude that (i) MCP-1 is strongly expressed in a small subset of cells in macrophage-rich regions of human and rabbit atherosclerotic lesions and (ii) MCP-1 may, therefore, play an important role in the ongoing recruitment of monocyte-macrophages into developing lesions in vivo. Images PMID:2052604

  5. Macrophage colony-stimulating factor mRNA and protein in atherosclerotic lesions of rabbits and humans.

    PubMed Central

    Rosenfeld, M. E.; Ylä-Herttuala, S.; Lipton, B. A.; Ord, V. A.; Witztum, J. L.; Steinberg, D.

    1992-01-01

    In this study, the authors demonstrate the expression of mRNA and the presence of protein for macrophage colony-stimulating factor (MCSF) in atherosclerotic lesions from humans and rabbits. In situ hybridization of serial sections of human fatty streaks demonstrated expression of MCSF mRNA by cells dispersed throughout the lesions. Immunocytochemical staining with a panel of MCSF-specific antibodies showed extensive cell-associated staining of all of the cell types in the lesions. Immunocytochemical studies of atherosclerotic lesions from Watanabe heritable hyperlipidemic (WHHL) and cholesterol-fed rabbits demonstrated a similar cell-associated pattern of staining. There was no MCSF-specific staining of aortas from normal rabbits or of cultured aortic smooth muscle cells from either humans or rabbits. Macrophage-derived foam cells (MFC) were isolated from the aortas of ballooned, cholesterol-fed rabbits. A Northern blot demonstrated that RNA isolated from the MFC hybridized with a human cDNA probe for MCSF. RNA from alveolar macrophages isolated simultaneously from the same rabbits did not hybridize with the MCSF probe. Conditioned media from an 18- to 24-hour incubation of the MFC contained colony-stimulating activity as demonstrated in a mouse bone marrow culture assay. Most of this colony-stimulating activity was neutralized by preincubating the conditioned media with an MCSF-specific antibody. Images Figure 2 Figure 1 Figure 1 Figure 3 PMID:1739123

  6. Validating a bimodal intravascular ultrasound (IVUS) and near-infrared fluorescence (NIRF) catheter for atherosclerotic plaque detection in rabbits

    PubMed Central

    Abran, Maxime; Stähli, Barbara E.; Merlet, Nolwenn; Mihalache-Avram, Teodora; Mecteau, Mélanie; Rhéaume, Eric; Busseuil, David; Tardif, Jean-Claude; Lesage, Frédéric

    2015-01-01

    Coronary artery disease is characterized by atherosclerotic plaque formation. Despite impressive advances in intravascular imaging modalities, in vivo molecular plaque characterization remains challenging, and different multimodality imaging systems have been proposed. We validated an engineered bimodal intravascular ultrasound imaging (IVUS) / near-infrared fluorescence (NIRF) imaging catheter in vivo using a balloon injury atherosclerosis rabbit model. Rabbit aortas and right iliac arteries were scanned in vivo after indocyanine green (ICG) injection, and compared to corresponding ex vivo fluorescence and white light images. Areas of ICG accumulation were colocalized with macroscopic atherosclerotic plaque formation. In vivo imaging was performed with the bimodal catheter integrating ICG-induced fluorescence signals into cross-sectional IVUS imaging. In vivo ICG accumulation corresponded to ex vivo fluorescence signal intensity and IVUS identified plaques. PMID:26504648

  7. Validating a bimodal intravascular ultrasound (IVUS) and near-infrared fluorescence (NIRF) catheter for atherosclerotic plaque detection in rabbits.

    PubMed

    Abran, Maxime; Stähli, Barbara E; Merlet, Nolwenn; Mihalache-Avram, Teodora; Mecteau, Mélanie; Rhéaume, Eric; Busseuil, David; Tardif, Jean-Claude; Lesage, Frédéric

    2015-10-01

    Coronary artery disease is characterized by atherosclerotic plaque formation. Despite impressive advances in intravascular imaging modalities, in vivo molecular plaque characterization remains challenging, and different multimodality imaging systems have been proposed. We validated an engineered bimodal intravascular ultrasound imaging (IVUS) / near-infrared fluorescence (NIRF) imaging catheter in vivo using a balloon injury atherosclerosis rabbit model. Rabbit aortas and right iliac arteries were scanned in vivo after indocyanine green (ICG) injection, and compared to corresponding ex vivo fluorescence and white light images. Areas of ICG accumulation were colocalized with macroscopic atherosclerotic plaque formation. In vivo imaging was performed with the bimodal catheter integrating ICG-induced fluorescence signals into cross-sectional IVUS imaging. In vivo ICG accumulation corresponded to ex vivo fluorescence signal intensity and IVUS identified plaques.

  8. [Ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance angiography combined with inflammatory factors for detecting atherosclerotic plaques in rabbits].

    PubMed

    Li, Gongxin; Wang, Luzhao; Liu, Peng; Wen, Zhibo; Huang, Fanheng; Chen, Liheng; Zhao, Xin; Lin, Lin; Zhou, Yijun

    2014-08-01

    To investigate the feasibility of Ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance angiography (USPIO-MRA) combined with interleukin-6 (IL-6) and IL-10 detection for detecting atherosclerotic plaques in rabbits. Twenty-four normal male rabbits were randomly assigned (n=8) into group A with atherosclerosis induced by damaging the aortic tunica intima with Foley's tube in combination with a high fat diet, group B with a high fat diet, and group C without any intervention. At week 12, plain and USPIO-MRA was performed in all the 24 rabbits and the results were compared with pathological examinations; blood samples were collected from the ear vein to examine blood lipids and levels of IL-6 and IL-10. The rabbits in groups A and B showed significantly different IL-6 levels (167 ± 21.3 vs 116 ± 14.3 pg/ml, P<0.05) but comparable blood lipids and IL-10 levels (P>0.05). The levels of IL-6, IL-10, TC, TG, and LDL, but not HDL, differed significantly between groups A and C and between groups B and C (P<0.01). Continuous MRA scan showed significantly different signal-to-noise ratios (SNR) between the 3 groups. USPIO-MRA combined with IL-6 and IL-10 detection is feasible in detecting atherosclerotic plaques in rabbits.

  9. Lipoprotein(a) Promotes Smooth Muscle Cell Proliferation and Dedifferentiation in Atherosclerotic Lesions of Human Apo(a) Transgenic Rabbits

    PubMed Central

    Ichikawa, Tomonaga; Unoki, Hiroyuki; Sun, Huijun; Shimoyamada, Hiroaki; Marcovina, Santica; Shikama, Hisataka; Watanabe, Teruo; Fan, Jianglin

    2002-01-01

    Elevated plasma lipoprotein(a) [Lp(a)] levels constitute an independent risk factor for the development of atherosclerosis. However, the mechanism underlying Lp(a) atherogenicity is unclear. Recently, we demonstrated that Lp(a) may potentially be proatherogenic in transgenic rabbits expressing human apolipoprotein(a) [apo(a)]. In this study, we further investigated atherosclerotic lesions of transgenic rabbits by morphometry and immunohistochemistry. On a cholesterol diet, human apo(a) transgenic rabbits had more extensive atherosclerotic lesions of the aorta, carotid artery, iliac artery, and coronary artery than did nontransgenic littermate rabbits as defined by increased intimal lesion area. Enhanced lesion development in transgenic rabbits was characterized by increased accumulation of smooth muscle cells, that was often associated with the Lp(a) deposition. To explore the possibility that Lp(a) may be involved in the smooth-muscle cell phenotypic modulation, we stained the lesions using a panel of monoclonal antibodies against smooth-muscle myosin heavy-chain isoforms (SM1, SM2, and SMemb) and basic transcriptional element binding protein-2 (BTEB2). We found that a large number of smooth muscle cells located in the apo(a)-containing areas of transgenic rabbits were positive for SMemb and BTEB2, suggesting that these smooth muscle cells were either immature or in the state of activation. In addition, transgenic rabbits showed delayed fibrinolytic activity accompanied by increased plasma plasminogen activator inhibitor-1. We conclude that Lp(a) may enhance the lesion development by mediating smooth muscle cell proliferation and dedifferentiation possibly because of impaired fibrinolytic activity. PMID:11786416

  10. Effects of linseed consumption for a short period of time on lipid profile and atherosclerotic lesions in rabbits fed a hypercholesterolaemic diet.

    PubMed

    Prim, Camila Rodrigues; Baroncini, Liz Andréa Villela; Précoma, Leonardo Brandão; Caron, Pedro Henrique Lamach; Winter, Guilherme; Poletti, Mônica Olímpia Dall'Oglio; Précoma, Dalton Bertolim

    2012-03-01

    Linseed contains biologically active substances, such as lignans, fibres and linoleic acid, which are believed to provide cardioprotective effects. The objective of the present study was to assess the potential hypolipaemic, anti-atherogenic and anti-inflammatory effects of linseed consumption using an experimental animal model, with rabbits fed a hypercholesterolaemic diet (1 % cholesterol extracted from lyophilised egg). A total of twenty white male rabbits were selected and divided into two groups: group I (GI), control group, ten rabbits; group II (GII), ten rabbits. The animals were fed a hypercholesterolaemic diet for 56 d. For the GII diet, ground linseed was added from day 29 through to day 56. Animals underwent aortic arch and descending aorta dissection on day 56 for histological, morphometric and immunohistochemical analysis. At the end of the experiment, GII animals presented with lower levels of total cholesterol (TC, 10 068·3 v. 16 767·0 mg/l; P < 0·05) and lower levels of LDL-cholesterol (LDL-C; 10 743·2 v. 15 961·2 mg/l; P < 0·05) when compared with the GI control group. There was no significant difference in serum HDL-cholesterol and TAG between the two groups. Almost all animals exhibited type III atherosclerotic lesions in the descending aorta. There was no statistically significant difference between the intima area and the intima:media layer area ratio in both groups. There was no difference between the positive areas for vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 molecules between the groups. Linseed consumption showed hypolipaemic action by reducing LDL-C and TC levels; however, this cholesterol-lowering effect did not reduce the atherosclerotic lesions induced by a hypercholesterolaemic diet (1 % cholesterol) for a short period of time.

  11. Intravascular photoacoustic imaging of atherosclerotic plaques: ex-vivo study using a rabbit model of atherosclerosis

    NASA Astrophysics Data System (ADS)

    Sethuraman, S.; Mallidi, S.; Aglyamov, S. R.; Amirian, J. H.; Litovsky, S.; Smalling, R. W.; Emelianov, S. Y.

    2007-02-01

    Diagnosis and treatment of atherosclerosis necessitates the detection and differentiation of rupture prone plaques. In principle, intravascular photoacoustic (IVPA) imaging has the ability to simultaneously visualize the structure and composition of atherosclerotic plaques by utilizing the difference in optical absorption. Extensive studies are required to validate the utility of IVPA imaging in detecting vulnerable plaques and address issues associated with the clinical implementation of the technique. In this work, we performed ex vivo imaging studies using a rabbit model of atherosclerosis. The intravascular photoacoustic (IVPA) and ultrasound (IVUS) images of the normal aorta and aorta with plaque were obtained and compared with histological slices of the tissue. The results indicate that IVPA imaging is capable of detecting plaques and showed potential in determining the composition. Furthermore, we initially addressed several aspects of clinical implementation of the IVPA imaging. Specifically, the configuration of combined IVPA and IVUS catheter was investigated and the effect of the optical absorption of the luminal blood on the IVPA image quality was evaluated. Overall, this study suggests that IVPA imaging can become a unique and important clinical tool.

  12. Preferential influx and decreased fractional loss of lipoprotein(a) in atherosclerotic compared with nonlesioned rabbit aorta.

    PubMed Central

    Nielsen, L B; Stender, S; Jauhiainen, M; Nordestgaard, B G

    1996-01-01

    The aim was to investigate the atherogenic potential of lipoprotein(a) (Lp(a)) and to further our understanding of the atherogenic process by measuring rates of transfer into the intima-inner media (i.e., intimal clearance) and rates of loss from the intima-inner media (i.e., fractional loss) of Lp(a) and LDL using cholesterol-fed rabbits with nonlesioned (n = 13) or atherosclerotic aortas (n = 12). In each rabbit, 131I-Lp(a) (or 131I-LDL) was injected intravenously 26 h before and 125I-Lp(a) (or 125I-LDL) 3 h before the aorta was removed and divided into six consecutive segments of similar size. The intimal clearance of Lp(a) and LDL was similar and markedly increased in atherosclerotic compared with nonlesioned aortas (ANOVA, effect of atherosclerosis: P < 0.0001). Fractional losses of labeled Lp(a) and labeled LDL in atherosclerotic aorta were on average 25 and 43%, respectively, of that in nonlesioned aortas (ANOVA, effect of atherosclerosis: P < 0.0001). Fractional loss of Lp(a) was 73% of that of LDL (ANOVA, effect of type of lipoprotein: P = 0.07). These data suggest that the development of atherosclerosis is associated with increased influx as well as decreased fractional loss of Lp(a) and LDL from the intima. Accordingly, Lp(a) may share with LDL the potential for causing atherosclerosis. PMID:8755669

  13. Selective ablation of WHHLMI rabbit atherosclerotic plaque by quantum cascade laser in the 5.7 μm wavelength range for less-invasive laser angioplasty

    NASA Astrophysics Data System (ADS)

    Hashimura, Keisuke; Ishii, Katsunori; Akikusa, Naota; Edamura, Tadataka; Yoshida, Harumasa; Awazu, Kunio

    2013-06-01

    We investigated the potential of a compact and high-power quantum cascade laser (QCL) in the 5.7 μm wavelength range for less-invasive laser angioplasty. Atherosclerotic plaques consist mainly of cholesteryl esters. Radiation at a wavelength of 5.75 μm is strongly absorbed in C=O stretching vibration mode of cholesteryl esters. Our previous study achieved to make cutting differences between a normal artery and an atherosclerotic lesions using nanosecond pulsed laser by difference-frequency generation (DFG laser) at the wavelength of 5.75 μm. For applying this technique to clinical treatment, a compact laser device is required. In this study, QCL irradiation effects to a porcine normal aorta were compared with DFG laser. Subsequently, QCL irradiation effects on an atherosclerotic aorta of myocardial infarction-prone Watanabe heritable hyperlipidemic rabbit (WHHLMI rabbit) and a normal rabbit aorta were observed. As a result, the QCL could make cutting differences between the rabbit atherosclerotic and normal aortas. On the other hand, the QCL induced more thermal damage to porcine normal aorta than the DFG laser at the irradiation condition of comparable ablation depths. In conclusion, the possibility of less-invasive and selective treatment of atherosclerotic plaques using the QCL in the 5.7 μm wavelength range was revealed, although improvement of QCL was required to prevent the thermal damage of a normal artery.

  14. Experimental Toxoplasmic Lymphadenopathy in Rabbits

    PubMed Central

    Henry, L.; Beverley, J. K. A.; Shortland, J. R.; Coup, A. J.

    1973-01-01

    The pathogenesis of toxoplasmic lymphadenopathy was studied in rabbits. Sixteen were infected with a high virulence strain of Toxoplasma gondii and 32 with one of low virulence. The former group were killed and examined at intervals up to 9 days and the latter up to 129 days. The high virulence strain quickly caused paracortical hyperplasia but only moderate follicular reaction. Later, lymphoid depletion occurred. The low virulence strain caused follicular reaction so that at 16 days germinal centres had developed with evidence of cellular phagocytosis. Histiocytes were present and plasma cells were found in the medullary cords. These appearances were seen up to 51 days. At 86 days the follicular reaction was no longer present but had returned at 129 days. These results were supplemented by serological, parasitological, immunofluorescence and electron microscopic data. The histological changes seen in the low virulence infections up to 51 days are unlike those caused by the high virulence strain but closely parallel those found in acquired infections in man, which are usually caused by strains of the low virulence type. These findings may help to elucidate the nature of the complex immune responses and the pathogenesis of toxoplasma infections. ImagesFigs. 14-15Figs. 16, 18 and 19Figs. 12-13Figs. 7-11Figs. 1-6 PMID:4577945

  15. Impaired muscarinic endothelium-dependent relaxation and cyclic guanosine 5'-monophosphate formation in atherosclerotic human coronary artery and rabbit aorta.

    PubMed Central

    Bossaller, C; Habib, G B; Yamamoto, H; Williams, C; Wells, S; Henry, P D

    1987-01-01

    The dependence of vascular relaxation on an intact endothelium and the relationship between relaxation and cyclic GMP accumulation were determined in coronary arteries isolated from cardiac transplantation patients with or without coronary atherosclerosis. In nonatherosclerotic arteries, the endothelium-dependent agent acetylcholine produced concentration-related relaxations. In atherosclerotic arteries, endothelium-dependent relaxations were abolished with acetylcholine, partly suppressed with substance P and histamine, and completely preserved with the ionophore A23187. In these arteries, the endothelium-independent agent nitroglycerin remained fully active. Accumulation of cyclic GMP in atherosclerotic strips was suppressed with acetylcholine but unattenuated with A23187 and nitroglycerin. In aortas from rabbits with diet-induced atherosclerosis, there was likewise an impaired cholinergic relaxation and cyclic GMP accumulation in the presence of preserved responses to A23187 and nitroglycerin. The results demonstrate that impaired cholinergic responses in atherosclerotic arteries reflect a muscarinic defect and not an inability of endothelium to release endothelial factor or smooth muscle to respond to it. PMID:2432088

  16. EXPERIMENTAL SYPHILIS IN THE RABBIT

    PubMed Central

    Brown, Wade H.; Pearce, Louise

    1920-01-01

    From the study of a large series of rabbits with outspoken manifestations of generalized syphilis, lesions of the skin and appendages were found to constitute one of the largest and most varied groups of such affections. The conditions noted consisted of alopecias, onychia and paronychia, and lesions of the skin proper. It was found to be a matter of some difficulty to make a positive diagnosis of syphilitic alopecia, but there were three and possibly four conditions which appeared to be attributable to such an infection. The first of these took the form of a general or local roughening of the coat with falling of the hair which produced the typical moth-eaten appearance associated with syphilitic alopecia in the human subject. A second form of alopecia was essentially an abnormal looseness of the hair which permitted large areas of the body to be completely denuded. The third type of alopecia was associated with definite skin changes, and the hair was readily removable together with an adherent mass of epithelial scales. Paronychia was comparatively rare but was readily recognized by a characteristic infiltration and exfoliation of the skin about the base of the nails. The incidence of onychia is uncertain. Late in the course of the investigation it was found that alterations in the nails which were not entirely characteristic in themselves might occur in consequence of a syphilitic involvement of the nail beds which could not be detected by ordinary methods of examination. The cases which were recognized as syphilitic were those which showed an associated paronychia. Lesions of the skin were found to be one of the most frequent manifestations of a generalized infection in the rabbit. These lesions were divided into three classes: first, granulomatous lesions, second, infiltrations, and third, erythemata. The granulomata were lesions of a fleshy character which tended to grow to a very large size and presented all the characteristics of circumscribed primary

  17. Evidence for the presence of oxidatively modified low density lipoprotein in atherosclerotic lesions of rabbit and man.

    PubMed Central

    Ylä-Herttuala, S; Palinski, W; Rosenfeld, M E; Parthasarathy, S; Carew, T E; Butler, S; Witztum, J L; Steinberg, D

    1989-01-01

    Three lines of evidence are presented that low density lipoproteins gently extracted from human and rabbit atherosclerotic lesions (lesion LDL) greatly resembles LDL that has been oxidatively modified in vitro. First, lesion LDL showed many of the physical and chemical properties of oxidized LDL, properties that differ from those of plasma LDL: higher electrophoretic mobility, a higher density, higher free cholesterol content, and a higher proportion of sphingomyelin and lysophosphatidylcholine in the phospholipid fraction. A number of lower molecular weight fragments of apo B were found in lesion LDL, similar to in vitro oxidized LDL. Second, both the intact apo B and some of the apo B fragments of lesion LDL reacted in Western blots with antisera that recognize malondialdehyde-conjugated lysine and 4-hydroxynonenal lysine adducts, both of which are found in oxidized LDL; plasma LDL and LDL from normal human intima showed no such reactivity. Third, lesion LDL shared biological properties with oxidized LDL: compared with plasma LDL, lesion LDL produced much greater stimulation of cholesterol esterification and was degraded more rapidly by macrophages. Degradation of radiolabeled lesion LDL was competitively inhibited by unlabeled lesion LDL, by LDL oxidized with copper, by polyinosinic acid and by malondialdehyde-LDL, but not by native LDL, indicating uptake by the scavenger receptor(s). Finally, lesion LDL (but not normal intimal LDL or plasma LDL) was chemotactic for monocytes, as is oxidized LDL. These studies provide strong evidence that atherosclerotic lesions, both in man and in rabbit, contain oxidatively modified LDL. Images PMID:2794046

  18. SCM-198 attenuates early atherosclerotic lesions in hypercholesterolemic rabbits via modulation of the inflammatory and oxidative stress pathways.

    PubMed

    Zhang, Yanfei; Guo, Wei; Wen, Yadan; Xiong, Qinghui; Liu, Hongrui; Wu, Jian; Zou, Yunzeng; Zhu, Yizhun

    2012-09-01

    GPx in the aorta. In a rabbit atherosclerotic model, SCM-198 dose-dependently ameliorated the progression of atherosclerotic lesions and vascular dysfunction accompanied by the suppression of inflammatory factors and oxidative stress. These findings suggested that SCM-198 might be a potential agent for the treatment of atherosclerosis. Crown Copyright © 2012. Published by Elsevier Ireland Ltd. All rights reserved.

  19. Monitoring plaque inflammation in atherosclerotic rabbits with an iron oxide (P904) and 18F-FDG using a combined PET/MR scanner

    PubMed Central

    Millon, A.; Dickson, S.D.; Klink, A.; Izquierdo-Garcia, D.; Bini, J.; Lancelot, E.; Ballet, S.; Robert, P.; de Castro, J. Mateo; Corot, C.; Fayad, Z.A.

    2014-01-01

    Purpose The aim of this study was to compare the ability of 18F-FDG PET and iron contrast-enhanced MRI with a novel USPIO (P904) to assess change in plaque inflammation induced by atorvastatin and dietary change in a rabbit model of atherosclerosis using a combined PET/MR scanner. Materials and methods Atherosclerotic rabbits underwent USPIO-enhanced MRI and 18F-FDG PET in PET/ MR hybrid system at baseline and were then randomly divided into a progression group (high cholesterol diet) and a regression group (chow diet and atorvastatin). Each group was scanned again 6 months after baseline imaging. R2* (i.e. 1/T2*) values were calculated pre/post P904 injection. 18F-FDG PET data were analyzed by averaging the mean Standard Uptake Value (SUVmean) over the abdominal aorta. The in vivo imaging was then correlated with matched histological sections stained for macrophages. Results 18F-FDG PET showed strong FDG uptake in the abdominal aorta and P904 injection revealed an increase in R2* values in the aortic wall at baseline. At 6 months, SUVmean values measured in the regression group showed a significant decrease from baseline (p =0.015). In comparison, progression group values remained constant (p =0.681). R2* values showed a similar decreasing trend in the regression group suggesting less USPIO uptake in the aortic wall. Correlations between SUVmean or Change in R2* value and macrophages density (RAM-11 staining) were good (R2 =0.778 and 0.707 respectively). Conclusion This experimental study confirms the possibility to combine two functional imaging modalities to assess changes in the inflammation of atherosclerotic plaques. 18F-FDG-PET seems to be more sensitive than USPIO P904 to detect early changes in plaque inflammation. PMID:23582588

  20. Monitoring plaque inflammation in atherosclerotic rabbits with an iron oxide (P904) and (18)F-FDG using a combined PET/MR scanner.

    PubMed

    Millon, A; Dickson, S D; Klink, A; Izquierdo-Garcia, D; Bini, J; Lancelot, E; Ballet, S; Robert, P; Mateo de Castro, J; Corot, C; Fayad, Z A

    2013-06-01

    The aim of this study was to compare the ability of (18)F-FDG PET and iron contrast-enhanced MRI with a novel USPIO (P904) to assess change in plaque inflammation induced by atorvastatin and dietary change in a rabbit model of atherosclerosis using a combined PET/MR scanner. Atherosclerotic rabbits underwent USPIO-enhanced MRI and (18)F-FDG PET in PET/MR hybrid system at baseline and were then randomly divided into a progression group (high cholesterol diet) and a regression group (chow diet and atorvastatin). Each group was scanned again 6 months after baseline imaging. R2* (i.e. 1/T2*) values were calculated pre/post P904 injection. (18)F-FDG PET data were analyzed by averaging the mean Standard Uptake Value (SUVmean) over the abdominal aorta. The in vivo imaging was then correlated with matched histological sections stained for macrophages. (18)F-FDG PET showed strong FDG uptake in the abdominal aorta and P904 injection revealed an increase in R2* values in the aortic wall at baseline. At 6 months, SUVmean values measured in the regression group showed a significant decrease from baseline (p = 0.015). In comparison, progression group values remained constant (p = 0.681). R2* values showed a similar decreasing trend in the regression group suggesting less USPIO uptake in the aortic wall. Correlations between SUVmean or Change in R2* value and macrophages density (RAM-11 staining) were good (R(2) = 0.778 and 0.707 respectively). This experimental study confirms the possibility to combine two functional imaging modalities to assess changes in the inflammation of atherosclerotic plaques. (18)F-FDG-PET seems to be more sensitive than USPIO P904 to detect early changes in plaque inflammation. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  1. Identifying Vulnerable Atherosclerotic Plaque in Rabbits Using DMSA-USPIO Enhanced Magnetic Resonance Imaging to Investigate the Effect of Atorvastatin.

    PubMed

    Qi, Chunmei; Deng, Liangrong; Li, Dongye; Wu, Weiheng; Gong, Lei; Li, Yong; Zhang, Qingdui; Zhang, Tao; Zhang, Chao; Zhang, Yu

    2015-01-01

    Rupture of an atherosclerotic plaque is the primary cause of acute cardiovascular and cerebrovascular syndromes. Early and non-invasive detection of vulnerable atherosclerotic plaques (VP) would be significant in preventing some aspects of these syndromes. As a new contrast agent, dimercaptosuccinic acid (DMSA) modified ultra-small super paramagnetic iron oxide (USPIO) was synthesized and used to identify VP and rupture plaque by magnetic resonance imaging (MRI). Atherosclerosis was induced in male New Zealand White rabbits by feeding a high cholesterol diet (n = 30). Group A with atherosclerosis plaque (n = 10) were controls. VP was established in groups B (n = 10) and C (n = 10) using balloon-induced endothelial injury of the abdominal aorta. Adenovirus-carrying p53 genes were injected into the aortic segments rich in plaques after 8 weeks. Group C was treated with atorvastatin for 8 weeks. Sixteen weeks later, all rabbits underwent pharmacological triggering, and imaging were taken daily for 5 d after DMSA-USPIO infusion. At the first day and before being killed, serum MMP-9, sCD40L, and other lipid indicators were measured. DMSA-USPIO particles accumulated in VP and rupture plaques. Rupture plaques appeared as areas of hyper-intensity on DMSA-USPIO enhanced MRI, especially T2*-weighted sequences, with a signal strength peaking at 96 h. The group given atorvastatin showed few DMSA-USPIO particles and had lower levels of serum indicators. MMP-9 and sCD40L levels in group B were significantly higher than in the other 2 groups (P <0.05). After successfully establishing a VP model in rabbits, DMSA-USPIO was used to enhance MRI for clear identification of plaque inflammation and rupture. Rupture plaques were detectable in this way probably due to an activating inflammatory process. Atorvastatin reduced the inflammatory response and stabilizing VP possibly by decreasing MMP-9 and sCD40L levels.

  2. Identifying Vulnerable Atherosclerotic Plaque in Rabbits Using DMSA-USPIO Enhanced Magnetic Resonance Imaging to Investigate the Effect of Atorvastatin

    PubMed Central

    Li, Dongye; Wu, Weiheng; Gong, Lei; Li, Yong; Zhang, Qingdui; Zhang, Tao; Zhang, Chao; Zhang, Yu

    2015-01-01

    Background Rupture of an atherosclerotic plaque is the primary cause of acute cardiovascular and cerebrovascular syndromes. Early and non-invasive detection of vulnerable atherosclerotic plaques (VP) would be significant in preventing some aspects of these syndromes. As a new contrast agent, dimercaptosuccinic acid (DMSA) modified ultra-small super paramagnetic iron oxide (USPIO) was synthesized and used to identify VP and rupture plaque by magnetic resonance imaging (MRI). Methods Atherosclerosis was induced in male New Zealand White rabbits by feeding a high cholesterol diet (n = 30). Group A with atherosclerosis plaque (n = 10) were controls. VP was established in groups B (n = 10) and C (n = 10) using balloon-induced endothelial injury of the abdominal aorta. Adenovirus-carrying p53 genes were injected into the aortic segments rich in plaques after 8 weeks. Group C was treated with atorvastatin for 8 weeks. Sixteen weeks later, all rabbits underwent pharmacological triggering, and imaging were taken daily for 5 d after DMSA-USPIO infusion. At the first day and before being killed, serum MMP-9, sCD40L, and other lipid indicators were measured. Results DMSA-USPIO particles accumulated in VP and rupture plaques. Rupture plaques appeared as areas of hyper-intensity on DMSA-USPIO enhanced MRI, especially T2*-weighted sequences, with a signal strength peaking at 96 h. The group given atorvastatin showed few DMSA-USPIO particles and had lower levels of serum indicators. MMP-9 and sCD40L levels in group B were significantly higher than in the other 2 groups (P <0.05). Conclusion After successfully establishing a VP model in rabbits, DMSA-USPIO was used to enhance MRI for clear identification of plaque inflammation and rupture. Rupture plaques were detectable in this way probably due to an activating inflammatory process. Atorvastatin reduced the inflammatory response and stabilizing VP possibly by decreasing MMP-9 and sCD40L levels. PMID:25973795

  3. Effect of Quercus infectoria and Rosa damascena on lipid profile and atherosclerotic plaque formation in rabbit model of hyperlipidemia.

    PubMed

    Gholamhoseinian, A; Shahouzehi, B; Joukar, S; Iranpoor, M

    2012-01-01

    Hyperlipidemia is the cause of many complications in the human societies. In this study, the effect of methanol extracts of Quercus infectoria (QI) galls and Rosa damascena (RD) Mill flower were studied on lipid profile and atherosclerotic plaques formation in hyperlipidemic rabbits. Thirty-six New Zeland white rabbits randomly divided into 6 groups as control (I), hyperlipidemic (II), hyperlipidemic+QI (III), hyperlipidemic+RD (IV), +Atorvastolin (V) and hyperlipidemic+Orlistat (VI) and were fed with high fat diet (0.5% cholesterol and 16% hydrogenated vegetable oil) for 45 days. At the end of the study period, lipid profile and plaque formation were assessed. Total Cholesterol (TC), Low Density Lipoprotein (LDL) and Triglyceride (TG) levels were significantly increased in hyperlipidemic group compared with control group (p < 0.001). Methanol extract consumption of Quercus infectoria significantly decreased plasma levels of TC, TG and LDL (p < 0.001). It also decreased plaques formation in semi lunar valve and thoracic aorta. Rosa damascena mill flower methanol extract moderately decreased the levels of TC, TG, LDL and plaques formation but it was not significant. HDL levels and weight of animals did not show significant difference among groups. Based on the doses used in this study, our finding indicated that QI but no RD methanol extract has anti atherogenic and hypolipidemic activities.

  4. High susceptibility of atherosclerotic coronary arteries to the onset of vasospasm and angina pectoris-like symptoms due to coronary spasm in WHHLMI rabbits

    PubMed Central

    Koike, Tomonari; Tamura, Shiori; Yu, Ying; Kuniyoshi, Nobue; Shiomi, Masashi

    2016-01-01

    We examined the relationship between atherosclerosis and the provocation of coronary spasm as well as the influence of coronary spasm on the onset of acute ischemic myocardial disease. Coronary spasm was provoked in anesthetized normal Japanese white (JW) rabbits and myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits, an animal model for coronary atherosclerosis and myocardial infarction, by injecting ergonovine during the infusion of norepinephrine through a marginal ear vein. A decrease in contrast flow in the left circumflex artery was observed on coronary angiograms. Ischemic changes were observed on the electrocardiograms of 29% (2/7) of JW and 79% (27/34, P=0.007) of WHHLMI rabbits. The frequency of coronary spasm was significantly high in rabbits with severe coronary plaques showing diffuse lesions. Left ventricle motility in vasospasm-positive rabbits, which was evaluated with echocardiograms, was decreased by 29% following the ergonovine injection (P<0.001), and every serum ischemic marker markedly increased 4 h after the provocation of vasospasm. These results demonstrate that atherosclerotic coronary arteries are positively related to the provocation of vasospasm, and vasospasm in severe atherosclerotic coronary segments evokes angina pectoris-like findings and/or non-fatal myocardial infarction. WHHLMI rabbits may be a novel animal model for angina pectoris and acute ischemic heart disease. PMID:27301847

  5. Experimental Studies of Two Replicated Atherosclerotic Carotid Bifurcations

    NASA Astrophysics Data System (ADS)

    Bale-Glickman, Jocelyn; Selby, Kathy; Saloner, David; Savas, Omer

    2004-11-01

    Detailed flow visualization and particle image velocimetry (PIV) studies are carried out at the stenosis in two atherosclerotic carotid bifurcation models under physiological flow conditions. Companion experiments are also carried out with sinusoidal and steady input flows. The complex internal geometry of the diseased artery combined with pulsatile input flows gives complex, model-specific flow patterns, with details that vary from cycle to cycle. Both models show a jet leaving the stenosis, with an associated recirculation zone on one side. Other flow features include separation points, recirculation zones, internal jets, three-dimensional shear layers, and stagnation lines. The wall shear stresses (WSS) are estimated from the PIV data. The profile WSS along the arterial lumen is unique for each artery, but similar profiles are observed for both physiological and steady flow for each artery. The WSS at the narrowest point in the stenotic neck varies chaotically from cycle to cycle, but typically ranges from 5 Pa to -40 Pa. The peak WSS values are found at peak systole.

  6. Experimental Infection of Rabbits with Rabbit and Genotypes 1 and 4 Hepatitis E Viruses

    PubMed Central

    Ma, Hongxia; Zheng, Lin; Liu, Yunbo; Zhao, Chenyan; Harrison, Tim J.; Ma, Yuyuan; Sun, Shuhua; Zhang, Jingang; Wang, Youchun

    2010-01-01

    Background A recent study provided evidence that farmed rabbits in China harbor a novel hepatitis E virus (HEV) genotype. Although the rabbit HEV isolate had 77–79% nucleotide identity to the mammalian HEV genotypes 1 to 4, their genomic organization is very similar. Since rabbits are used widely experimentally, including as models of infection, we investigated whether they constitute an appropriate animal model for human HEV infection. Methods Forty-two SPF rabbits were divided randomly into eleven groups and inoculated with six different isolates of rabbit HEV, two different doses of a second-passage rabbit HEV, and with genotype 1 and 4 HEV. Sera and feces were collected weekly after inoculation. HEV antigen, RNA, antibody and alanine aminotransferase in sera and HEV RNA in feces were detected. The liver samples were collected during necropsy subject to histopathological examination. Findings Rabbits inoculated with rabbit HEV became infected with HEV, with viremia, fecal virus shedding and high serum levels of viral antigens, and developed hepatitis, with elevation of the liver enzyme, ALT. The severity of disease corresponded to the infectious dose (genome equivalents), with the most severe hepatic disease caused by strain GDC54-18. However, only two of nine rabbits infected with HEV genotype 4, and none infected with genotype 1, developed hepatitis although six of nine rabbits inoculated with the genotype 1 HEV and in all rabbits inoculated with the genotype 4 HEV seroconverted to be positive for anti-HEV IgG antibody by 14 weeks post-inoculation. Conclusions These data indicate that rabbits are an appropriate model for rabbit HEV infection but are not likely to be useful for the study of human HEV. The rabbit HEV infection of rabbits may provide an appropriate parallel animal model to study HEV pathogenesis. PMID:20161794

  7. Effect of pollen extract on the development of experimental atherosclerosis in rabbits.

    PubMed

    Wójcicki, J; Samochowiec, L; Bartłomowicz, B; Hinek, A; Jaworska, M; Gawrońska-Szklarz, B

    1986-10-01

    Our previous studies have shown that the pollen extract, Cernitin, reveals lipid-lowering properties in animals and humans. The present study was designed to investigate the influence of Cernitin on the development of experimental atherosclerosis in rabbits over a period of 12 weeks. Forty male mongrel rabbits were divided into 4 equal groups: (1) controls, (2) animals receiving high-fat diet (HFD) containing cholesterol and coconut oil, (3) HFD + pollen extract, and (4) HFD + clofibrate. The most pronounced reduction in lipid metabolism and in the severity of plaque formation occurred after the pollen extract had been applied. The total cholesterol content in serum and liver homogenate was depressed by 67% and 45%, respectively, while the serum HDL cholesterol and alpha-lipoproteins level was increased by 19% and from 7.73% to 21.73% respectively. The cytochrome P-450 content in the liver microsomes was elevated by 98% (nmol/g liver). Atherosclerotic plaque intensity at 12 weeks, measured planimetrically, averaged 85.5% in HFD-fed animals vs 33.7% in pollen extract-treated rabbits. These findings suggest that Cernitin, in addition to significantly lowering serum lipid levels in rabbits on an experimental diet, may modify lipid deposition in major arteries.

  8. Effect of garlic supplementation on erythrocytes antioxidant parameters, lipid peroxidation, and atherosclerotic plaque formation process in oxidized oil-fed rabbits.

    PubMed

    Zalejska-Fiolka, Jolanta; Kasperczyk, Aleksandra; Kasperczyk, Sławomir; Błaszczyk, Urszula; Birkner, Ewa

    2007-01-01

    Effect of garlic supplementation on blood antioxidant status, lipid peroxidation, and coronary plaque formation process was investigated in oxidized oil-fed rabbits. Eighteen adult male mixed European rabbits were given a balanced diet (21 g% protein, 34 g% fat, 45 g% carbohydrate), which contained isocaloristic addition of nonoxidized or oxidized rapeseed oil in the presence and absence of garlic. The experiment lasted 24 weeks. At the beginning and every 6 weeks, rabbits were weighed, and blood was taken. To evaluate the antioxidant status of the rabbits, erythrocytes malondialdehyde (MDA) concentration, total superoxide dismutase (t-SOD), and glutathione peroxidase (GPX) activations were determined. After the experiment was completed, aortas were dissected for histological examinations. Changes in the contents of the above parameters and histological examinations showed that oxidized rapeseed, oil administered to rabbits, caused the development of atherosclerotic changes and disturbed antioxidant status. The addition of garlic in such diets inhibited atherosclerotic changes in the aorta wall, and it is related to the homeostatic activity of antioxidative enzymes and lipid peroxidation.

  9. The Arginine/ADMA Ratio Is Related to the Prevention of Atherosclerotic Plaques in Hypercholesterolemic Rabbits When Giving a Combined Therapy with Atorvastatine and Arginine

    PubMed Central

    Brinkmann, Saskia J. H.; Wörner, Elisabeth A.; Buijs, Nikki; Richir, Milan; Cynober, Luc; van Leeuwen, Paul A. M.; Couderc, Rémy

    2015-01-01

    Supplementation with arginine in combination with atorvastatin is more efficient in reducing the size of an atherosclerotic plaque than treatment with a statin or arginine alone in homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits. We evaluated the mechanism behind this feature by exploring the role of the arginine/asymmetric dimethylarginine (ADMA) ratio, which is the substrate and inhibitor of nitric oxide synthase (NOS) and thereby nitric oxide (NO), respectively. Methods: Rabbits were fed either an arginine diet (group A, n = 9), standard rabbit chow plus atorvastatin (group S, n = 8), standard rabbit chow plus an arginine diet with atorvastatin (group SA, n = 8) or standard rabbit chow (group C, n = 9) as control. Blood was sampled and the aorta was harvested for topographic and histological analysis. Plasma levels of arginine, ADMA, cholesterol and nitric oxide were determined and the arginine/ADMA ratio was calculated. Results: The decrease in ADMA levels over time was significantly correlated to fewer aortic lesions in the distal aorta and total aorta. The arginine/ADMA ratio was correlated to cholesterol levels and decrease in cholesterol levels over time in the SA group. A lower arginine/ADMA ratio was significantly correlated to lower NO levels in the S and C group. Discussion: A balance between arginine and ADMA is an important indicator in the prevention of the development of atherosclerotic plaques. PMID:26035753

  10. Anti-atherosclerotic effects of perilla oil in rabbits fed a high-cholesterol diet

    PubMed Central

    Cha, Yeseul; Jang, Ja Young; Ban, Young-Hwan; Guo, Haiyu; Shin, Kyungha; Kim, Tae-Su; Lee, Sung-Pyo; Choi, Jieun; An, Eun-Suk; Seo, Da-Woom; Yon, Jung-Min

    2016-01-01

    Anti-atherosclerosis effects of perilla oil were investigated, in comparison with lovastatin, in rabbits fed a high-cholesterol diet (HCD). Hypercholesterolemia was induced in rabbits by feeding the HCD containing 0.5% cholesterol and 1% corn oil, and perilla oil (0.1 or 0.3%) was added to the diet containing 0.5% cholesterol for 10 weeks. HCD greatly increased blood total cholesterol and low-density lipoproteins, and caused thick atheromatous plaques, covering 74% of the aortic wall. Hyper-cholesterolemia also induced lipid accumulation in the liver and kidneys, leading to lipid peroxidation. Perilla oil not only attenuated hypercholesterolemia and atheroma formation, but also reduced fat accumulation and lipid peroxidation in hepatic and renal tissues. The results indicate that perilla oil prevents atherosclerosis and fatty liver by controlling lipid metabolism, and that it could be the first choice oil to improve diet-induced metabolic syndrome. PMID:27729934

  11. In vivo detection of macrophages in a rabbit atherosclerotic model by time-resolved laser-induced fluorescence spectroscopy

    PubMed Central

    Marcu, Laura; Fang, Qiyin; Jo, Javier A.; Papaioannou, Thanassis; Dorafshar, Amir; Reil, Todd; Qiao, Jian-Hua; Baker, J. Dennis; Freischlag, Julie A.; Fishbein, Michael C.

    2007-01-01

    Accumulation of numerous macrophages in the fibrous cap is a key identifying feature of plaque inflammation and vulnerability. This study investigates the use of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) as a potential tool for detection of macrophage foam cells in the intima of atherosclerotic plaques. Experiments were conducted in vivo on 14 New Zealand rabbits (6 control, 8 hypercholesterolemic) following aortotomy to expose the intimal luminal surface of the aorta. Tissue autofluorescence was induced with a nitrogen pulse laser (337 nm, 1 ns). Lesions were histologically classified by the percent of collagen or macrophage foam cells as well as thickness of the intima. Using parameters derived from the time-resolved fluorescence emission of plaques, we determined that intima rich in macrophage foam cells can be distinguished from intima rich in collagen with high sensitivity (>85%) and specificity (>95%). This study demonstrates, for the first time, that a time-resolved fluorescence-based technique can differentiate and demark macrophage content versus collagen content in vivo. Our results suggest that TR-LIFS technique can be used in clinical applications for identification of inflammatory cells important in plaque formation and rupture. PMID:16039283

  12. Anti-atherosclerotic effects of garlic preparation in freeze injury model of atherosclerosis in cholesterol-fed rabbits.

    PubMed

    Sobenin, Igor A; Andrianova, Irina V; Lakunin, Konstantin Y; Karagodin, Vasilii P; Bobryshev, Yuri V; Orekhov, Alexander N

    2016-10-15

    Garlic (Allium sativum L.) is one of the most popular substances used to reduce various risks associated with cardiovascular disease. However, little is known on the direct effects of garlic on atherosclerosis. In the present study we have examined the effect of per oral administration of the time-released garlic herbal preparation on serum atherogenicity and formation of intimal thickening after freeze injury in cholesterol-fed rabbits. Group 1 rabbits maintained on the standard cholesterol-rich diet served as the control. Group 2 rabbits were fed the cholesterol-rich diet and treated with garlic preparation containing 300 mg garlic powder. Local thickening of the aortic media (i.e., the neointima formation) in the freeze injury zone was observed in all the rabbits. Regular garlic preparation therapy prevented the neointima formation and the accumulation of free and esterified cholesterol, triglycerides, phospholipids and collagen in the neointima, the effects being statistically significant. Garlic preparation also decreased serum lipid content by 1.5-fold and lowered atherogenic activity of blood serum (ability to induce lipid accumulation in cultured cells) induced by cholesterol-rich diet. The results obtained indicate that garlic preparation prevents the development of cholesterol-induced experimental atherosclerosis and possesses the direct anti-atherogenic activity. Copyright © 2015 Elsevier GmbH. All rights reserved.

  13. Experimental rabbit models of Chlamydia pneumoniae infection.

    PubMed Central

    Moazed, T. C.; Kuo, C.; Patton, D. L.; Grayston, J. T.; Campbell, L. A.

    1996-01-01

    Chlamydia pneumoniae (TWAR), a common cause of acute respiratory disease in humans, has recently been associated with coronary and aortic atherosclerosis. In this study, we evaluated rabbit models of chlamydial infection to investigate the pathogenesis of C. pneumoniae infection. New Zealand White rabbits were inoculated intranasally and intratracheally with C. pneumoniae, strain AR-39, and primary and repeated infection were assessed. After a single inoculation, lung pathology was characterized by a moderate self-resolving interstitial pneumonia with bronchiolitis of 21 days in duration. Chlamydial DNA was detected by polymerase chain reaction (PCR) intermittently in the upper respiratory tract and lung tissue through day 21 postinoculation, spleen tissue at day 14, and peripheral blood mononuclear cells at days 3 and 21. After repeated inoculations, chlamydial DNA was detected by PCR in the upper respiratory tract and lung tissue through day 42. Lung lesions consisted of multifocal interstitial mononuclear cell aggregates that persisted up to day 42. Watanabe heritable hyperlipidemic rabbits were less susceptible to C. pneumoniae infection. After multiple inoculations of Watanabe rabbits, C. pneumoniae was detected by PCR and/or immunocytochemistry until day 21. In conclusion, C. pneumoniae induced a moderate respiratory infection in these rabbit models. Images Figure 1 Figure 2 Figure 3 PMID:8579129

  14. Comedogenicity of sunscreens. Experimental observations in rabbits.

    PubMed

    Mills, O H; Kligman, A M

    1982-06-01

    Fourteen of 29 proprietary sunscreen formulations, including suntan promoters, were found to be comedogenic when applied to the external ear canal of albino rabbits. Ultraviolet exposures enhanced the comedogenic effect. The vehicles, rather than the UV-absorbing compounds, seemed to be responsible. accordingly, sunscreen acne may be a subtype of acne cosmetica. A sampling of UV absorbers showed these agents to be noncomedogenic.

  15. Pharmacological modulation by celecoxib of cachexia associated with experimental arthritis and atherosclerosis in rabbits

    PubMed Central

    Romero, FI; Martínez-Calatrava, MJ; Sánchez-Pernaute, O; Gualillo, O; Largo, R; Herrero-Beaumont, G

    2010-01-01

    BACKGROUND AND PURPOSE Non-steroidal anti-inflammatory drugs improve inflammatory cachexia in several conditions. Thus, we have explored inhibition of cyclooxygenase-2 (COX-2) in an experimental model of rheumatoid cachexia in rabbits. EXPERIMENTAL APPROACH Chronic arthritis was induced in immunized rabbits by repeated intra-articular injections of ovalbumin. To increase the degree of systemic inflammation and also to induce atherosclerotic lesions, the animals were fed a hyperlipidaemic diet (2% cholesterol and 6% peanut oil) and were given an endothelial injury of the femoral artery. Rabbits were randomized to receive the COX-2 inhibitor celecoxib (10 mg·kg−1·day−1) or no treatment. After 4 weeks, sera, peripheral mononuclear cells and vessel specimens were collected. KEY RESULTS Inhibition of COX-2 by celecoxib modulated the systemic inflammatory response and increased total cholesterol and triglyceride levels. Celecoxib also minimized weight loss and prevented serum albumin fall. At a vascular level, celecoxib reduced COX-2 protein in the femoral arterial wall, but did not modify size or the macrophage infiltration of femoral lesions nor the percentage of rabbits with spontaneous aortic plaques. CONCLUSIONS AND IMPLICATIONS Our animal model induced a severe inflammatory cachexia, comparable to that of persistently active rheumatoid arthritis. The inhibition of COX-2 by celecoxib improves this state, suggesting that COX products play an important role in its development, without affecting the development or the progression of vascular lesions. Overall, these results suggest that celecoxib might be considered as a new therapeutic tool for the treatment of rheumatoid cachexia. PMID:20633016

  16. Rabbit as an animal model for experimental research.

    PubMed

    Mapara, Manjeet; Thomas, Betsy Sara; Bhat, K M

    2012-01-01

    Animal experimentation is carried out in consultation with the veterinary wing but it is essential that be familiar with experimental protocols of animal model to be able to design an approriate study. This is more so in place where the veterinary facilities are not easily available.Span Rabbits are commonly used as subjects for screening implant material. They have gained favour for their numerous advantages even though they should be ideally used prior to testing in a larger animal model. Though experimentation on rabbits seems to be easy there are many pitfalls. Our endeavor in this article is to integrate all the data about maintaining rabbits as a model and to critically analyze it on the basis of our experimentation.

  17. Neurogenic cardiomyopathy in rabbits with experimentally induced rabies.

    PubMed

    Kesdangsakonwut, S; Sunden, Y; Yamada, K; Nishizono, A; Sawa, H; Umemura, T

    2015-05-01

    Cardiomyopathies have been rarely described in rabbits. Here we report myocardial necrosis of the ventricular wall in rabbits with experimentally induced rabies. Myocardial lesions were found only in rabbits with brain lesions, and the severity of the cardiac lesions was proportional to that of the brain lesions. Neither the frequency nor the cumulative dose of anesthesia was related to the incidence or the severity of the myocardial lesions. The myocardial lesions were characterized by degeneration and/or necrosis of myocardial cells and were accompanied by contraction band necrosis, interstitial fibrosis, and infiltration of inflammatory cells. The brain lesions due to rabies virus infection were most prominent in the cerebral cortex, thalamus, hypothalamus, brainstem, and medulla. Rabies virus antigen was not found in the hearts of any rabbits. Based on these findings, the myocardial lesions were classified as neurogenic cardiomyopathy.

  18. Persistence of rabbit haemorrhagic disease virus genome in vaccinated rabbits after experimental infection.

    PubMed

    Gall, A; Schirrmeier, H

    2006-10-01

    Rabbit haemorrhagic disease (RHD) is usually a fatal disease in rabbits which has spread rapidly across the continents. While previous studies suggested persistence in rabbits to be an important factor in the epidemiology, the relevance of field virus infection of immune rabbits has not been investigated in experimentally infected animals before. This report describes for the first time the persistence of rabbit haemorrhagic disease virus (RHDV) genome for at least 15 weeks in rabbits immunized with an inactivated vaccine as well as a subunit vaccine and subsequently challenged with virulent RHDV. The viral RNA loads were determined by real-time reverse transcription-polymerase chain reaction. No conspicuous association of the detectable amount of RHDV RNA with the type of vaccine, the time after infection and--with one exception--the level of RHDV-specific antibodies in the immunized animals was observed. The results presented in this study are an urgent evidence for the existence of carrier animals as an important factor in the epidemiology of RHD.

  19. Effects of positive acceleration on the metabolism of endogenous carbon monoxide and serum lipid in atherosclerotic rabbits

    PubMed Central

    Luo, Huilan; Chen, Yongsheng; Wang, Junhua

    2010-01-01

    Background: Atherosclerosis (AS) is caused mainly due to the increase in the serum lipid, thrombosis, and injuries of the endothelial cells. During aviation, the incremental load of positive acceleration that leads to dramatic stress reactions and hemodynamic changes may predispose pilots to functional disorders and even pathological changes of organs. However, much less is known on the correlation between aviation and AS pathogenesis. Methods and Results: A total of 32 rabbits were randomly divided into 4 groups with 8 rabbits in each group. The control group was given a high cholesterol diet but no acceleration exposure, whereas the other 3 experimental groups were treated with a high cholesterol diet and acceleration exposure for 4, 8, and 12 weeks, respectively. In each group, samples of celiac vein blood and the aorta were collected after the last exposure for the measurement of endogenous CO and HO-1 activities, as well as the levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). As compared with the control group, the endocardial CO content and the HO-1 activity in aortic endothelial cells were significantly elevated at the 4th, 8th, and 12th weekend, respectively (P < 0.05 or <0.01). And these measures tended upward as the exposure time was prolonged. Levels of TC and LDL-C in the experimental groups were significantly higher than those in the control group, presenting an upward tendency. Levels of TG were found significantly increased in the 8-week-exposure group, but significantly declined in the 12-week-exposure group (still higher than those in the control group). Levels of the HDL-C were increased in the 4-week-exposure group, declined in the 8-week-exposure group, and once more increased in the 12-week-exposure group, without significant differences with the control group. Conclusions: Positive acceleration exposure may lead to a significant increase of

  20. Hypolipidemic effect of arborium plus in experimentally induced hypercholestermic rabbits.

    PubMed

    Murty, Devarakonda; Rajesh, Enjamoori; Raghava, Doonaboina; Raghavan, Tangaraj Vijaya; Surulivel, Mukanthan Karupiah Munirajan

    2010-06-01

    Hypercholesteremia is one of the risk factors for coronary artery disease. The present study highlights the efficacy of the ayurvedic herbal formulation Arborium Plus [Hyppophae ramnoides L. fruit juice (S) and Rhododendron arboreum Sm. Linn flower juice (R) in a 1:4 ratio] on triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), atherogenic index (AI), high-density lipoprotein (HDL), and high-sensitivity c-reactive protein (hs CRP) in experimentally induced hypercholesterolemic rabbits. Four groups of rabbits were subjected to different treatments for 8 weeks: control group, CHOL group (1% w/w cholesterol for 8 weeks), S+R group (1% w/w cholesterol and Arborium Plus for 8 weeks), and A group (1% w/w cholesterol and atorvastatin for 8 weeks). The results showed significant increases in TG, TC, LDL, AI, and hs CRP in hypercholesterolemic rabbits which was significantly reduced in Arborium Plus-treated hypercholesterolemic rabbits. The data demonstrated that the Arborium Plus formulation was associated with hypolipidemic effects in experimentally induced hypercholesterolemic rabbits.

  1. Different effects of estrogen and progesterone on experimental atherosclerosis in female versus male rabbits. Quantification of cellular proliferation by bromodeoxyuridine.

    PubMed

    Hanke, H; Hanke, S; Finking, G; Muhic-Lohrer, A; Mück, A O; Schmahl, F W; Haasis, R; Hombach, V

    1996-07-15

    The aim of the present study was to compare the effect of estrogen and progesterone on the development of experimental atherosclerosis in female versus male rabbits to assess possible sex-specific differences. A total of 32 female and 32 male New Zealand White rabbits were ovariectomized or castrated. In addition to a 0.5% cholesterol diet, the rabbits received estradiol alone (1 mg/kg body wt [BW] per week), progesterone alone (25 mg/kg BW per week), or combined estradiol-progesterone in these dosages during 12 weeks. Ovariectomized female and castrated male rabbits served as control groups without hormone treatment. Before excision of the vessels, bromodeoxyuridine labeling was performed to determine the extent of cellular proliferation in the atherosclerotic lesions. The aortic arch was analyzed immunohistologically and morphometrically. An inhibitory effect of estrogen on intimal plaque size was found in female rabbits compared with the ovariectomized control group (0.7 +/- 0.5 versus 3.7 +/- 2.5 mm2, P < .002; proliferating cells, 3.1 +/- 1.8% versus 8.5 +/- 2.6%, P < .002). In combination with progesterone, however, estrogen was not able to reduce intimal plaque size or cellular proliferation. In contrast, estradiol in castrated male rabbits was not associated with an inhibitory effect on cellular proliferation or intimal thickening compared with controls (estrogen treatment, 7.6 +/- 2.1% proliferating cells and 2.8 +/- 1.0 mm2 neointima; control group, 7.2 +/- 2.1% cellular proliferation and 2.9 +/- 1.2 mm2 intimal thickening). Our data suggest that the atheroprotective effect of estrogen is probably due to a mechanism that is present in female rabbits only.

  2. Experimental infection of wild-caught European rabbits (Oryctolagus cuniculus) with Sarcoptes scabiei from a naturally infected wild rabbit.

    PubMed

    Millán, J; Casais, R; Colomar, V; Bach, E; Prieto, J M; Velarde, R

    2013-06-01

    Scabies was recently reported for the first time in the European wild rabbit, Oryctolagus cuniculus (Lagomorpha: Leporidae). We experimentally exposed 10 seronegative wild-caught rabbits to skin from a mangy wild rabbit. Serological, physiological, parasitological and histopathological changes were recorded. Three rabbits developed antibodies at 2-5 weeks post-infection (w.p.i.), two of which then developed lesions at 7 w.p.i. One of these had a small area of alopecia on the hind limb that healed naturally within 1 week; the other developed more extensive lesions restricted to the hind limbs (as typically observed in wild rabbits) that lasted until the rabbit died (12.5 w.p.i.). The third rabbit died of trauma 5 w.p.i. before developing any lesions. Antibodies in the healed rabbit disappeared from serum at 8 w.p.i., whereas antibody levels in the sick rabbit increased until its death. Disseminated intravascular coagulation and hepatic necrosis, probably arising from a concomitant infection with rabbit haemorrhagic disease virus, were the likely final cause of death in this rabbit. The mangy rabbit that served as a donor died of a multifocal fibrinosuppurative pneumonia that may have been secondary to the skin bacterial pyoderma.

  3. Experimental infections with Fasciola in snails, mice and rabbits.

    PubMed

    Hussein, Abdel-Nasser A; Khalifa, R M A

    2008-05-01

    Experimental infection trails of Lymnaea (cailliaudi) natalensis snails with miracidia of Fasciola hepatica revealed neither cercariae nor larval stages shed. Infection of white mice with metacercariae from field-collected snails proved to be negative for Fasciola eggs and immature juveniles or adults after 84 days post infection. The infection of eight rabbits (Oryctolagus cuniculus) has succeeded; two rabbits were infected, with a very low infection rate. Faeces of rabbits were negative for eggs. The worm burden was one and three worms from 40 fed metacercariae. The obtained fluke measures 23 mm in length by 4 mm in width. The tegument is covered with sharp-ending spines. The uterus contains few eggs. The intrauterine eggs measured 158 microm x 80 microm. According to the morphological characters of these flukes, they belong to F. gigantica.

  4. Detection and localization of rabbit hepatitis e virus and antigen in systemic tissues from experimentally intraperitoneally infected rabbits.

    PubMed

    Mao, Jingjing; Zhao, Yue; She, Ruiping; Cao, Binbin; Xiao, Peng; Wu, Qiaoxing; Guo, Zhaojie; Ma, Longhuan; Soomro, Majid Hussain

    2014-01-01

    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.

  5. Overexpression of Mitofusin 2 inhibited oxidized low-density lipoprotein induced vascular smooth muscle cell proliferation and reduced atherosclerotic lesion formation in rabbit

    SciTech Connect

    Guo Yanhong; Chen Kuanghueih; Gao Wei; Li Qian; Chen Li; Wang Guisong Tang Jian

    2007-11-16

    Our previous studies have implies that Mitofusin 2 (Mfn2), which was progressively reduced in arteries from ApoE{sup -/-} mice during the development of atherosclerosis, may take part in pathogenesis of atherosclerosis. In this study, we found that overexpression of Mfn2 inhibited oxidized low-density lipoprotein or serum induced vascular smooth muscle cell proliferation by down-regulation of Akt and ERK phosphorylation. Then we investigated the in vivo role of Mfn2 on the development of atherosclerosis in rabbits using adenovirus expressing Mitofusin 2 gene (AdMfn2). By morphometric analysis we found overexpression of Mfn2 inhibited atherosclerotic lesion formation and intima/media ratio by 66.7% and 74.6%, respectively, compared with control group. These results suggest that local Mfn2 treatment suppresses the development of atherosclerosis in vivo in part by attenuating the smooth muscle cell proliferation induced by lipid deposition and vascular injury.

  6. MEMS thermal sensors to detect changes in heat transfer in the pre-atherosclerotic regions of fat-fed New Zealand white rabbits.

    PubMed

    Yu, Fei; Ai, Lisong; Dai, Wangde; Rozengurt, Nora; Yu, Hongyu; Hsiai, Tzung K

    2011-06-01

    Real-time detection of pre-atherosclerotic regions remains an unmet clinical challenge. We previously demonstrated the application of micro-electro-mechanical systems (MEMS) to detect changes in convective heat transfer in terms of sensor output voltages in the zone of flow reversal in an in vitro stenotic model. We hereby demonstrated changes in sensor output voltages in the pre-atherosclerotic regions in the New Zealand White rabbits fed on hypercholesterolemic diet (HD). After 8 weeks, we observed that mean output voltages (V(ave)) were similar in the distal aortic arch, thoracic, and abdominal aortas in the normal standard diet (ND) group, consistent with an absence of atherosclerosis. In HD group, V(ave) increased in the distal aortic arch (HD: V(ave) = 1.05 ± 0.04 V; ND: V(ave) = 0.12 ± 0.01 V, n = 3, p < 0.05) and in the thoracic aortas (HD: V(ave) = 0.72 ± 0.06 V; ND: V(ave) = 0.13 ± 0.024 V, n = 3, p < 0.05), consistent with the histological presence of pre-atherosclerosis. Despite HD diet, V (ave) magnitudes were similar to ND group in the abdominal aortas (HD: V(ave) = 0.14 ± 0.003 V; ND: V(ave) = 0.14 ± 0.004 V, n = 3), corroborating histological absence of pre-atherosclerosis. Hence, MEMS thermal sensors provide a new approach to detect changes in convective heat transfer in the pre-atherosclerotic regions.

  7. In vitro and in vivo investigations on the effects of low-density lipoprotein concentration polarization and haemodynamics on atherosclerotic localization in rabbit and zebrafish

    PubMed Central

    Xie, Xiang; Tan, Ju; Wei, Dangheng; Lei, Daoxi; Yin, Tieying; Huang, Junli; Zhang, Xiaojuan; Qiu, Juhui; Tang, Chaojun; Wang, Guixue

    2013-01-01

    Atherosclerosis (AS) commonly occurs in the regions of the arterial tree with haemodynamic peculiarities, including local flow field disturbances, and formation of swirling flow and vortices. The aim of our study was to confirm low-density lipoprotein (LDL) concentration polarization in the vascular system in vitro and in vivo, and investigate the effects of LDL concentration polarization and flow field alterations on atherosclerotic localization. Red fluorescent LDL was injected into optically transparent Flk1: GFP zebrafish embryos, and the LDL distribution in the vascular lumen was investigated in vivo using laser scanning confocal microscopy. LDL concentration at the vascular luminal surface was found to be higher than that in the bulk. The flow field conditions in blood vessel segments were simulated and measured, and obvious flow field disturbances were found in the regions of vascular geometry change. The LDL concentration at the luminal surface of bifurcation was significantly higher than that in the straight segment, possibly owing to the atherogenic effect of disturbed flow. Additionally, a stenosis model of rabbit carotid arteries was generated. Atherosclerotic plaques were found to have occurred in the stenosis group and were more severe in the stenosis group on a high-fat diet. Our findings provide the first ever definite proof that LDL concentration polarization occurs in the vascular system in vivo. Both lipoprotein concentration polarization and flow field changes are involved in the infiltration/accumulation of atherogenic lipids within the location of arterial luminal surface and promote the development of AS. PMID:23449959

  8. Effect of pioglitazone on inflammation and calcification in atherosclerotic rabbits : An (18)F-FDG-PET/CT in vivo imaging study.

    PubMed

    Xu, J; Nie, M; Li, J; Xu, Z; Zhang, M; Yan, Y; Feng, T; Zhao, X; Zhao, Q

    2017-09-27

    We developed an atherosclerotic rabbit model and tested pioglitazone as a drug intervention for early vascular calcification. Positron emission tomography/computed tomography (PET/CT) was used to evaluate inflammation and therapeutic effects. We randomly divided 20 male New Zealand white rabbits into a pioglitazone-treated group (n = 10) and a control group (n = 10). Atherosclerosis was induced via a high-cholesterol diet and endothelial denudation. The animals were maintained on a hyperlipidemic diet for 16 weeks after surgery, and the treatment group received pioglitazone daily. Serum samples were obtained at 8 and 18 weeks postoperatively to assess high-sensitivity C‑reactive protein (hs-CRP) and matrix metalloproteinase-9 (MMP-9) concentrations. Sixteen rabbits underwent a mid-stage PET/CT scan at week 8, and 11 rabbits underwent an end-stage PET/CT scan at week 18. PET/CT parameters, including the mean standardized uptake value (SUVmean) and maximum standardized uptake value (SUVmax), were measured and documented. There were significantly lower hs-CRP and MMP-9 levels in the pioglitazone group at week 18 (p < 0.01). At the end of the 8th week, no significant between-group differences in SUVmean and SUVmax were observed. From week 8 to week 18, the SUVmean and SUVmax decreased in the pioglitazone group but the SUVmean increased in the control group, with significant between-group differences at the end of the 18th week (p < 0.01). Histopathological examination of aortas in the control and pioglitazone groups revealed significantly smaller plaque area, macrophage density, and tissue calcification area in the latter group. Pioglitazone affects early vascular microcalcification, and pioglitazone-induced changes can be assessed using (18)F-FDG-PET/CT.

  9. Reported analgesic administration to rabbits undergoing experimental surgical procedures.

    PubMed

    Coulter, Claire A; Flecknell, Paul A; Leach, Matthew C; Richardson, Claire A

    2011-02-21

    It has become widely accepted that whenever animals are used in scientific procedures, the 3Rs principle of replacement, reduction and refinement described by William Russell and Rex Burch should be adhered to. Animals should be replaced with non-sentient alternatives if possible, the number of animals used should be reduced and experimental procedures should be refined to minimise pain, suffering and distress. Administration of analgesic agents to animals undergoing surgical procedures is a refinement used to alleviate pain. In this study, a structured literature review was carried out to examine current trends in analgesic administration to rabbits undergoing experimental surgical procedures. 128 papers from 51 peer-reviewed journals were selected for inclusion in this review. Reporting administration of systemic analgesia to rabbits in peer-reviewed scientific papers increased significantly from 16% to 50% between 1995-1997 and 2005-2007 (P < 0.001). Papers that reported ethical approval were more likely than papers that did not specify approval to report systemic analgesic administration (P < 0.001). When systemic analgesics were administered, buprenorphine was the most frequently used agent and non-steroidal anti-inflammatory drugs were used less frequently than opioids in both time periods. Although this review provides evidence that systemic analgesic administration to rabbits undergoing surgical procedures is increasing, rabbits do not always receive analgesia when they undergo experimental surgery. Other practices in rabbit perioperative care that could be improved, highlighted by this survey include: 1) changing the timing of analgesic administration by giving systemic analgesics pre- or perioperatively rather than only postoperatively, 2) using multimodal analgesia when pain is likely to be moderate to severe and 3) increasing the use of non-steroidal anti-inflammatory drugs and use of other techniques such as epidural analgesia particularly for

  10. Selective ablation of rabbit atherosclerotic plaque with less thermal effect by the control of pulse structure of a quantum cascade laser in the 5.7 μm wavelength range

    NASA Astrophysics Data System (ADS)

    Hashimura, Keisuke; Ishii, Katsunori; Awazu, Kunio

    2016-03-01

    Cholesteryl esters are main components of atherosclerotic plaques and have an absorption peak at the wavelength of 5.75 μm originated from C=O stretching vibration mode of ester bond. Our group achieved the selective ablation of atherosclerotic lesions using a quantum cascade laser (QCL) in the 5.7 μm wavelength range. QCLs are relatively new types of semiconductor lasers that can emit mid-infrared range. They are sufficiently compact and considered to be useful for clinical application. However, large thermal effects were observed because the QCL worked as quasicontinuous wave (CW) lasers due to its short pulse interval. Then we tried macro pulse irradiation (irradiation of pulses at intervals) of the QCL and achieved effective ablation with less-thermal effects than conventional quasi-CW irradiation. However, lesion selectivity might be changed by changing pulse structure. Therefore, in this study, irradiation effects of the macro pulse irradiation to rabbit atherosclerotic plaque and normal vessel were compared. The macro pulse width and the macro pulse interval were set to 0.5 and 12 ms, respectively, because the thermal relaxation time of rabbit normal and atherosclerotic aortas in the oscillation wavelength of the QCL was 0.5-12 ms. As a result, cutting difference was achieved between rabbit atherosclerotic and normal aortas by the macro pulse irradiation. Therefore, macro pulse irradiation of a QCL in the 5.7 μm wavelength range is effective for reducing thermal effects and selective ablation of the atherosclerotic plaque. QCLs have the potential of realizing less-invasive laser angioplasty.

  11. COMPLEMENT-FIXATION TITERS IN EXPERIMENTAL COCCIDIOIDOMYCOSIS IN RABBITS1

    PubMed Central

    Brosbe, Edwin A.; Kietzman, Jewell N.; Kurnick, Nathaniel B.

    1964-01-01

    Brosbe, Edwin A. (Veterans Administration Hospital, Long Beach, Calif.), Jewell N. Kietzman, and Nathaniel B. Kurnick. Complement-fixation titers in experimental coccidioidomycosis. J. Bacteriol. 88:233–241. 1964.—The course of experimental coccicioidomycosis in rabbits was followed with complement-fixation (CF) tests. Uniformity of complement-fixing antibody response to large infective doses was observed, and levels as high as 1:4,096 in the New Zealand albino and 1:16,384 in the Dutch rabbit were attained. Mortality reflected the size of the inoculum rather than the level of CF titer. Animals receiving additional challenges displayed no marked elevation in titer, although high titers persisted. Nitrogen mustard, for the most part, did not influence the CF titer. Images PMID:14197893

  12. Effect of local heating on restenosis and in-stent neointimal hyperplasia in the atherosclerotic rabbit model: a dose-ranging study.

    PubMed

    Brasselet, Camille; Durand, Eric; Addad, Faouzi; Vitry, Fabien; Chatellier, Gilles; Demerens, Corinne; Lemitre, Mathilde; Garnotel, Roselyne; Urbain, Dominique; Bruneval, Patrick; Lafont, Antoine

    2008-02-01

    In-stent restenosis is related to neointimal hyperplasia. Heating reduces neointimal hyperplasia but promotes constrictive remodeling after balloon angioplasty. We aimed to assess the ability of local heating in inhibiting restenosis and in-stent neointimal hyperplasia and its potential side effects on arterial thrombosis. Atherosclerotic-like lesions were induced in iliac rabbit arteries. One month later, both iliac rabbit arteries were stented. In each animal, one artery was randomized to local heating at four temperatures (50, 60, 80, and 100 degrees C). The contra lateral artery was used as control. Angiographic and histomorphometric analysis were performed 42 days after angioplasty. Immunohistochemistry was performed 3, 15, and 42 days after angioplasty. Angiographic significant reduction of in-stent restenosis after moderate heating (50 degrees C) was related to in-stent neointimal hyperplasia trend to be lower after moderate local heating when compared with controls. In contrast, in-stent thrombosis was similar to controls. Higher temperatures (i.e. 80 and 100 degrees C) also reduced in-stent neointimal hyperplasia but were most frequently associated with severe in-stent thrombosis. Local heating was associated with decreased cell proliferation, collagen density, and increased smooth muscle cell apoptosis and heat shock protein expression. Moderate heating represents a promising approach to prevent in-stent restenosis via the limitation of the proliferative response without thrombosis induction.

  13. In vivo distribution of single chain variable fragment (scFv) against atherothrombotic oxidized LDL/β2-glycoprotein I complexes into atherosclerotic plaques of WHHL rabbits: Implication for clinical PET imaging.

    PubMed

    Sasaki, Takanori; Kobayashi, Kazuko; Kita, Shoichi; Kojima, Kazuo; Hirano, Hiroyuki; Shen, Lianhua; Takenaka, Fumiaki; Kumon, Hiromi; Matsuura, Eiji

    2017-02-01

    Oxidized LDL (oxLDL) can exist as a complex with β2-glycoprotein I (β2GPI) in plasma/serum of patients with non-autoimmune atherosclerotic disease or antiphospholipid syndrome (APS). Nonetheless, direct in vivo evidence supporting the pathophysiological involvement of oxLDL/β2GPI complexes and specific autoantibody against the complexes in developing atherothrombosis has yet been established. In the present study, we demonstrated in vivo distribution of single chain variable fragment of IgG anti-oxLDL/β2GPI complexes (3H3-scFv) in Watanabe heritable hyperlipidemic (WHHL) rabbits by PET/CT imaging. An antibody-based PET probe, (64)Cu-3H3-scFv, was established, and WHHL rabbits were applied for a non-autoimmune atherosclerotic model to demonstrate in vivo distribution of the probe. 3H3-scFv has exhibits specificity towards β2GPI complexed with oxLDL but neither a free form of β2GPI nor oxLDL alone. Post-intravenous administration of (64)Cu-3H3-scFv into WHHL rabbits has demonstrated a non-invasive approach for in vivo visualization of atherosclerotic lesion. The imaging probe achieved ideal blood clearance and distribution for optimal imaging capacity in 24h, significantly shorter than that of an intact IgG-based imaging probe. (64)Cu-3H3-scFv targeted on atherosclerotic plaques in aortas of WHHL rabbits where extensive accumulation of lipid deposits was observed by lipid staining and autoradiography. The accumulation of (64)Cu-3H3-scFv in aortic segments of WHHL rabbits was 2.8-folds higher than that of controls (p=0.0045). The present in vivo evidence supports the pathophysiological involvement of oxLDL/β2GPI complexes in atherosclerotic complications of WHHL rabbits. (64)Cu-3H3-scFv represents a novel PET imaging probe for non-invasive pathophysiological assessment of oxLDL/β2GPI complexes accumulated in atherosclerotic plaques. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Experimental model of cutaneous radiation injury in rabbits.

    PubMed

    Meirelles, Rafael Panisi de Campos; Hochman, Bernardo; Helene Junior, Americo; Lellis, Rute; Fraga, Murillo Francisco Pires; Ferreira, Lydia Masako

    2013-11-01

    To describe an experimental model of cutaneous radiation injury in rabbits. On this study eight six-month-old New Zealand male rabbits, with an average weight of 2.5 kg 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. 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 3000 cGy 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. The proposed experimental model is reproductable. This study suggests that the dosage 4500 cGy is excessive and the 3000 cGy is the most effective for this experimental model of cutaneous radiation injury in rabbits.

  15. [Experimental study regarding the ureteral cicatrization pattern in rabbit].

    PubMed

    Pintilie, R A; Grigorovici, Mirela

    2008-01-01

    This study aimed to elaborate an experimental model for ureteral cicatrization following surgical lesion, with direct involvement in urological therapy. The study was realized on a group of 9 female rabbits on which we have performed ureteral surgery. First surgical event consisted in partial cut of the left ureter following transperitoneal approach, ureteral stent insertion and the suture of the ureteral wound. The second surgical event has accomplished the harvesting of the ureteral fragment during cicatrisation process and was performed at various times from the first surgical event, accordingly at 1, 2, 3...6 days--on different rabbits. 3 rabbits composed the witness group. Fragments were fixed in formol 4%, and histologically stained with hematoxilin-eosin and van Gieson. In the first two days we have observed an obvious inflammatory process on the postoperative ureteral scar. In days 3 and 4, the limited fibrosis appeared in the 2nd day engaged a peak in the 4th day when appeared a sketch of ureteral lumen constriction. In the 5th and 6th day the fibrosis process underwent a moderate resolution, simultaneously with a local diffuse congestion, marker for the remodeling processes of the connective matrix. Animal cicatrisation model follows the same pattern as in human but at different timing so as extrapolation requires considering these facts.

  16. Carob pod insoluble fiber exerts anti-atherosclerotic effects in rabbits through sirtuin-1 and peroxisome proliferator-activated receptor-γ coactivator-1α.

    PubMed

    Valero-Muñoz, María; Martín-Fernández, Beatriz; Ballesteros, Sandra; Lahera, Vicente; de las Heras, Natalia

    2014-09-01

    The aim of this study was to evaluate the potential effects of an insoluble dietary fiber from carob pod (IFC) (1 g ⋅ kg(-1) ⋅ d(-1) in the diet) on alterations associated with atherosclerosis in rabbits with dyslipidemia. Male New Zealand rabbits (n = 30) were fed the following diets for 8 wk: 1) a control diet (SF412; Panlab) as a control group representing normal conditions; 2) a control supplemented with 0.5% cholesterol + 14% coconut oil (DL) (SF302; Panlab) for 8 wk as a dyslipidemic group; and 3) a control containing 0.5% cholesterol + 14% coconut oil plus IFC (1 g ⋅ kg(-1) ⋅ d(-1)) (DL+IFC) for 8 wk. IFC was administered in a pellet mixed with the DL diet. The DL-fed group developed mixed dyslipidemia and atherosclerotic lesions, which were associated with endothelial dysfunction, inflammation, and fibrosis. Furthermore, sirtuin-1 (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) protein expression in the aorta were reduced to 77% and 63% of the control group, respectively (P < 0.05), in these rabbits. Administration of IFC to DL-fed rabbits reduced the size of the aortic lesion significantly (DL, 15.2% and DL+IFC, 2.6%) and normalized acetylcholine-induced relaxation (maximal response: control, 89.3%; DL, 61.6%; DL+IFC, 87.1%; P < 0.05) and endothelial nitric oxide synthase expression (DL, 52% and DL+IFC, 104% of the control group). IFC administration to DL-fed rabbits also reduced cluster of differentiation 36 (DL, 148% and DL+IFC, 104% of the control group; P < 0.05), plasminogen activator inhibitor-1 (DL, 141% and DL+IFC, 107% of the control group), tumor necrosis factor-α (DL, 166% and DL+IFC, 120% of the control group), vascular cell adhesion molecule-1 (DL, 153% and DL+IFC, 110% of the control group), transforming growth factor-β (DL, 173% and DL+IFC, 99% of the control group), and collagen I (DL, 157% and DL+IFC, 112% of the control group) in the aorta. These effects were accompanied by an enhancement of

  17. Experimental magnesium depletion in adult rabbits caused by blast overpressure.

    PubMed

    Cernak, I; Radosevic, P; Malicevic, Z; Savic, J

    1995-09-01

    The complex pressure wave (blast) generated by some explosions causes pulmonary pathological changes which resemble the histological findings of the adult respiratory distress syndrome (ARDS). The development of indirect neurotrauma following experimental pulmonary blast injury has been shown previously. The purpose of this study was to evaluate lung and brainstem total tissue magnesium concentrations in adult rabbits following pulmonary blast injury. In order to assess the interrelationship between magnesium and other secondary injury factors, total calcium and high energy phosphate (phosphocreatine, PCr; adenosine triphosphate, ATP) contents were simultaneously measured. Twenty adult male rabbits were divided into two groups. Group C (n = 10) served as control, while group B (n = 10) was subjected to a focused blast wave, generated in laboratory conditions using an air-driven shock tube. Moderate pulmonary blast injury was verified by histological examination in group B. Total tissue magnesium and calcium contents were measured by atomic absorption spectrophotometry in the lungs and brainstem of adult rabbits 30 min following blast overpressure and in their uninjured controls. Simultaneously, PCr and ATP contents were measured by fluorimetric enzymatic analyses in same structures. Lung and brainstem water contents were determined by wet weight to dry weight ratio. Blast overpressure to the lungs induced significant magnesium depletion, increased calcium and decreased the Mg/Ca ratio in lung tissue of injured animals. Increases in water content and PCr/ATP ratio were also observed. Significant correlations between these Mg/Ca and PCr/ATP and between Mg and ATP parameters confirmed the functional relationship between magnesium depletion and impaired bioenergetic state in indirect neurotrauma in adult rabbits through blast overpressure.

  18. Experimental intracameral injection of vancomycin microparticles in rabbits.

    PubMed

    Kodjikian, Laurent; Couprie, Jérémy; Hachicha, Walid; Timour, Quadiri; Devouassoux, Mojgan; Builles, Nicolas; Hartmann, Daniel; Fessi, Hatem

    2010-08-01

    To evaluate the in vivo toxicity and efficacy of previously developed poly-(lactide-co-glycolide)-vancomycin-based microparticles (V-MPLs) for eventual use for endophthalmitis prophylaxis during cataract surgery. The intraocular vancomycin concentration profile was evaluated after V-MPL injection into the anterior chamber of rabbit eyes. The toxicology of V-MPLs versus MPLs alone was tested by corneal cellular counting and retinal histology. The prophylactic efficacy of the V-MPLs was evaluated by bacterial counts after introducing contaminated intraocular lenses (IOLs) together with the V-MPLs into one anterior chamber of phakic rabbit eyes or without V-MPLs in control rabbit eyes. Intraocular V-MPLs produced effective vancomycin concentrations over at least 6 hours. Corneal counts revealed no significant increase in dead cells. Retinal toxicity manifested as inflammation 3 hours after injection, reaching its maximum between 12 hours and 24 hours, decreasing by 48 hours, and completely disappearing at 72 hours. Inflammation was similar between V-MPLs and MPLs. Untreated eyes implanted with highly infected IOLs showed severe, reproducible endophthalmitis. No sign of infection was observed with infected IOLs and concomitant V-MPL treatment, supported by bacterial counts showing a significant decrease in colony-forming Staphylococcus epidermidis units in the anterior chamber and on the implant surfaces within 6 hours. The present study demonstrated the release and toxicologic properties of the authors' newly developed V-MPLs in vivo. In addition, the rabbit model shows that V-MPLs are effective in reducing the risk of experimental endophthalmitis.

  19. Effects of apple juice on risk factors of lipid profile, inflammation and coagulation, endothelial markers and atherosclerotic lesions in high cholesterolemic rabbits

    PubMed Central

    Setorki, Mahbubeh; Asgary, Sedighe; Eidi, Akram; rohani, Ali Haeri; Esmaeil, Nafiseh

    2009-01-01

    Background Atherosclerosis which results from gradual deposition of lipids in medium and large arteries is a leading cause of mortality worldwide. The objective of this study was to determine the effect of apple juice on some risk factors of atherosclerosis and on the development of atherosclerosis in rabbits fed a high-cholesterol diet. Methods Thirty two male rabbits were randomly divided into four groups: normal diet, high cholesterol diet (%1 cholesterol), 1% cholesterol supplemented with 5 ml apple juice (low dose) and 1% cholesterol supplemented with 10 ml apple juice (high dose) for 2 month. The C-reactive protein (CRP), nitrite, nitrate, fibrinogen, total cholesterol(TC) and factor VII were measured before the experiment and by the end of period. At the end of study, fatty streak formation in right and left coronary arteries were determined using Chekanov method in all groups. Results Both doses of apple juice significantly were decreased TC, TG, CRP, fibrinogen, factor VII levels, atherosclerotic lesion in right and left coronary arteries and increased nitrite and nitrate compared to cholesterolemic diet. Also using 10 ml apple juice caused significant reduce in LDL-C and increase HDL-C, but 5 ml apple juice did not change these factors. Significant differences were observed between 5 and 10 ml apple juice groups by LDL-C. No significant difference was found between 5 and 10 ml apple juice groups with regard to CRP, nitrite, nitrate, fibrinogen, factor VII, TG, HDL-C and TC concentrations. Conclusion Apple juice can effectively prevent the progress of atherosclerosis. This is likely due to antioxidant and anti-inflammatory effect of apple juice. PMID:19804641

  20. Contrast-enhanced B-mode US angiography in the assessment of experimental in vivo and in vitro atherosclerotic disease.

    PubMed

    Sirlin, C B; Lee, Y Z; Girard, M S; Peterson, T M; Steinbach, G C; Baker, K G; Mattrey, R F

    2001-02-01

    This study was performed to (a) test the hypothesis that filling the arterial lumen with echoes at B-mode ultrasound (US) enables the assessment of wall and luminal abnormalities and (b) compare contrast material-enhanced B-mode US with color and power Doppler US angiography. Atherosclerotic lesions were created in 14 rabbit aortas and imaged with color Doppler and B-mode US before and after the intravenous administration of 0.3 mL of AF0150, a US contrast agent. In addition, four replicas of diseased human carotid arteries were immersed in a tissue-mimicking phantom and imaged with B-mode and color and power Doppler US before and after the administration of 1 mL of AF0150 per liter of porcine blood. Radiopaque plastic casts of the rabbit aortas and contact radiographs of the plastic replicas served as standards. Although color and power Doppler US allowed immediate localization of the lumen, precise estimation of stenoses and reliable visualization of surface irregularities were not possible. After AF0150 administration, angiogram-like images of the lumen were created with B-mode US, allowing rapid assessment of the entire vessel lumen and wall. Consequently, luminal stenoses were more accurately measured than with unenhanced B-mode US (r2 = 0.94, P < .0001 vs r2 = 0.21, P = .25) or Doppler (r2 = 0.42, P < .03). In addition, plaques and ulcerations were visible only with contrast-enhanced B-mode US. Microbubbles fill the arterial lumen with echoes at B-mode US, creating an angiogram-like image. The ability to visualize the inner and outer surfaces of the vascular wall improved the evaluation of luminal and wall abnormalities.

  1. Macrophage-derived foam cells freshly isolated from rabbit atherosclerotic lesions degrade modified lipoproteins, promote oxidation of low-density lipoproteins, and contain oxidation-specific lipid-protein adducts.

    PubMed Central

    Rosenfeld, M E; Khoo, J C; Miller, E; Parthasarathy, S; Palinski, W; Witztum, J L

    1991-01-01

    Pure macrophage-derived foam cells (MFC) were isolated from the aortas of rabbits made atherosclerotic by balloon deendothelialization followed by diet-induced hypercholesterolemia. The MFC were isolated under sterile conditions using an enzymatic digestion procedure and discontinuous density gradient centrifugation. The purity of the MFC preparations was verified immunocytochemically with the macrophage specific monoclonal antibody RAM-11. MFC plated in medium containing 0.5% FCS for 24 h contained approximately 600 micrograms cholesterol per mg cell protein, 80% of which was esterified cholesterol. The MFC specifically degraded low density lipoprotein (LDL), acetyl-LDL, copper oxidized LDL, and beta-very low density lipoprotein (beta-VLDL) at rates comparable to mouse peritoneal macrophages (MPM) in 5-h assays. MFC within sections of the atherosclerotic lesions from the ballooned rabbits as well as the MFC isolated from the same lesions in the presence of antioxidants, exhibited positive immunoreactivity with polyclonal guinea pig antisera and mouse monoclonal antibodies directed against malondialdehyde-LDL, and 4-hydroxynonal-LDL. The MFC also exhibited the capacity to induce the oxidation of LDL at rates comparable to those exhibited by MPM and rabbit aortic endothelial cells. These data provide direct evidence that arterial wall macrophages express modified LDL receptors in vivo, contain epitopes found in oxidized-LDL and are capable of oxidizing LDL even when maximally loaded with cholesterol. Images PMID:1985115

  2. SPF rabbits infected with rabbit hepatitis E virus isolate experimentally showing the chronicity of hepatitis.

    PubMed

    Han, Jian; Lei, Yaxin; Liu, Lin; Liu, Peng; Xia, Junke; Zhang, Yulin; Zeng, Hang; Wang, Lin; Wang, Ling; Zhuang, Hui

    2014-01-01

    This study focused on investigating the pathogenesis seen in specific-pathogen-free (SPF) rabbits following infection with a homologous rabbit HEV isolate (CHN-BJ-rb14) and comparing it to that seen following infection with a heterologous swine genotype 4 HEV isolate (CHN-XJ-SW13). Three of the four animals inoculated with the homologous rabbit HEV became infected, exhibiting an intermittent viremia, obvious fluctuations of liver function biomarkers alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and persistent fecal virus shedding throughout the nine month study. In addition, liver histopathology showed both chronic inflammation and some degree of fibrosis. Both positive and negative-stranded HEV RNA and HEV antigen expression were detected in liver, brain, stomach, duodenum and kidney from the necropsied rabbits. Inflammation of extrahepatic tissue (duodenum and kidney) was also observed. Three of the four rabbits inoculated with the heterologous genotype 4 swine HEV also became infected, showing similar levels of anti-HEV antibody to that generated following infection with the homologous virus isolate. The duration of both viremia and fecal shedding of virus was however shorter following infection with the heterologous virus and there was no significant elevation of liver function biomarkers. These results suggest that rabbit HEV infection may cause more severe hepatitis and prolong the course of the disease, with a possible chronic trend of hepatitis in SPF rabbits.

  3. SPF Rabbits Infected with Rabbit Hepatitis E Virus Isolate Experimentally Showing the Chronicity of Hepatitis

    PubMed Central

    Han, Jian; Lei, Yaxin; Liu, Lin; Liu, Peng; Xia, Junke; Zhang, Yulin; Zeng, Hang; Wang, Lin; Wang, Ling; Zhuang, Hui

    2014-01-01

    This study focused on investigating the pathogenesis seen in specific-pathogen-free (SPF) rabbits following infection with a homologous rabbit HEV isolate (CHN-BJ-rb14) and comparing it to that seen following infection with a heterologous swine genotype 4 HEV isolate (CHN-XJ-SW13). Three of the four animals inoculated with the homologous rabbit HEV became infected, exhibiting an intermittent viremia, obvious fluctuations of liver function biomarkers alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and persistent fecal virus shedding throughout the nine month study. In addition, liver histopathology showed both chronic inflammation and some degree of fibrosis. Both positive and negative-stranded HEV RNA and HEV antigen expression were detected in liver, brain, stomach, duodenum and kidney from the necropsied rabbits. Inflammation of extrahepatic tissue (duodenum and kidney) was also observed. Three of the four rabbits inoculated with the heterologous genotype 4 swine HEV also became infected, showing similar levels of anti-HEV antibody to that generated following infection with the homologous virus isolate. The duration of both viremia and fecal shedding of virus was however shorter following infection with the heterologous virus and there was no significant elevation of liver function biomarkers. These results suggest that rabbit HEV infection may cause more severe hepatitis and prolong the course of the disease, with a possible chronic trend of hepatitis in SPF rabbits. PMID:24937350

  4. An experimental model of urethral stricture in rabbits using holmium laser under urethroscopic direct visualization.

    PubMed

    Hu, Wei-Feng; Li, Cui-Ling; Zhang, Hui-Ping; Li, Ting-Ting; Zeng, Xiao-Yong

    2014-01-01

    To establish an experimental rabbit model of urethral stricture using holmium laser under direct urethroscopic visualization. Sixteen adult male New Zealand rabbits were divided into equally-sized control and experimental groups. All rabbits underwent retrograde urethrography and transurethral endoscopy with a 7.5 F urethroscope after intramuscular anesthetic injection. We used a holmium:YAG laser to injure the distal urethra in all rabbits in the experimental group under direct visualization. Thirty days after surgery, all animals were evaluated with retrograde urethrography and urethroscopy. The flow rate of the isolated urethras was measured to evaluate urethral stricture formation. One rabbit in the experimental group (12.5%) died of infection 4 days after surgery. Thirty days after surgery, retrograde urethrography and urethroscopy revealed strictures in all seven surviving rabbits (87.5%) in the experimental group. The mean flow rate of the isolated urethras was significantly lower in the experimental group than in the control group. A rabbit model of urethral stricture can be successfully established using holmium laser under direct urethroscopic visualization, providing an ideal object for research concerning the pathogenesis and molecular biology of urethral strictures. © 2014 S. Karger AG, Basel.

  5. An experimental model of ischemia in rabbit hindlimb.

    PubMed Central

    Hong, J. H.; Bahk, Y. W.; Suh, J. S.; Kwak, B. K.; Shim, H. J.; Kim, J. S.; Kim, H. S.; Moon, Y. H.; Kim, S. J.; Chung, J. W.; Park, J. H.

    2001-01-01

    This study was performed to establish an experimental model of ischemia for the investigation of new treatment modality of limb-threatening ischemia. We produced ischemia in the hindlimbs of 8 New Zealand white rabbits. Under general anesthesia, the left femoral artery was exposed, freed, and excised from distal external iliac artery to proximal popliteal and saphenous arteries. And then both hindlimbs were serially examined to assess the ischemia according to the time table until postoperative 6 weeks. We assessed clinical observation, blood pressure, radioisotopic perfusion scan, and angiography. Clinical ischemic changes of the operated feet were observed in 63%. The blood pressure of left calves was measurable on postoperative day 3 (p<0.05, vs preoperative day 2) and then gradually increased to reach a plateau in postoperative week 6. Radioisotopic arterial perfusion showed similar profiles as in blood pressure. Angiography of ischemic hindlimbs demonstrated a few collateral vessels arising from the internal iliac artery with the reconstitution of the posterior tibial artery in postoperative week 2. In postoperative week 6, collaterals remained the same in number. However, these became dilated and tortuous and showed reconstitution in distal hindleg. In conclusion, this is a reproducible, measurable, and economical animal model of hind limb ischemia. PMID:11641535

  6. Transcatheter Arterial Embolization for Malignant Osseous and Soft-Tissue Sarcomas. I. A Rabbit Experimental Model

    SciTech Connect

    Nagata, Yasushi; Fujiwara, Kazuhisa; Okajima, Kaoru; Mitsumori, Michihide; Mizowaki, Takashi; Ohya, Natsuo; Hiraoka, Masahiro; Abe, Mitsuyuki; Ohura, Koitirou; Wataya, Shigeki

    1998-05-15

    Purpose: To evaluate the effect of transcatheter arterial embolization (TAE) on metastatic bone tumors in an experimental study. Methods: Fifteen Japanese white rabbits were transplanted with VX2 sarcoma cells into the iliac crest. In 10 rabbits, the arterial supply to the iliac bone tumors, internal iliac artery and iliolumbar artery were then embolized with particles of gelatin sponge. The therapeutic effect was evaluated by comparison with the natural course of control tumors in the other five rabbits. Results: After TAE, extensive necrosis, fibrosis, and vacuolization within the tumors were confirmed histologically. In the control rabbits, 19% {+-} 7% of the entire tumor was found to be spontaneous tumor necrosis; in contrast, the tumors of the TAE group showed necrosis as 62% {+-} 22% of the entire tumor. In one TAE group rabbit, no active tumor cell could be detected in the residual tumor. Conclusion: TAE was found to be an effective treatment for bone tumors in an experimental model.

  7. PSITTACOSIS : III. EXPERIMENTALLY INDUCED INFECTIONS IN RABBITS AND GUINEA PIGS.

    PubMed

    Rivers, T M; Berry, G P

    1931-06-30

    1. Rabbits and guinea pigs are susceptible to psittacosis virus introduced intracerebrally. By means of brain to brain passages in these animals the active agent is capable of propagation indefinitely. 2. Serial passages of the virus through rabbits and guinea pigs do not cause the active agent to lose its pathogenicity for parrots and mice. 3. The chief clinical evidences of infection in rabbits and guinea pigs following intracranial inoculation of the virus are fever and loss of weight. The pathological changes are characterized by a mild meningo-encephalitis, and fatty degeneration, focal necrosis, and infarction of the liver. 4. Rabbits upon recovery from an attack of psittacosis are actively immune. 5. Two strains of virus, human and parrot, were found to be immunologically similar. 6. No evidence was obtained to show that human convalescent serum possesses an appreciable amount of neutralizing substances.

  8. An Experimental Fluid dynamics Study of Exact-Replica Atherosclerotic Carotid Bifurcations

    NASA Astrophysics Data System (ADS)

    Bale-Glickman, Jocelyn; Selby, Kathy; Saloner, David; Savas, Omer

    2003-11-01

    Physiological flow studies are carried out in two different models of atherosclerotic carotid bifurcations using flow visualization and particle image velocimetry (PIV). The flow models exactly replicate the lumen of plaques excised intact from patients with severe atherosclerosis. A boundary treatment technique is employed in PIV processing to estimate the flow strain rate near the wall, hence to estimate the wall shear stresses (WSS) to a first order accuracy. The systolic and diastolic Reynolds numbers are about 900 and 300, respectively, which match Doppler Ultrasound scans done on the patients just before surgery. The complex internal geometry of the diseased artery combined with the pulsatile input flows gives exceedingly complex flow patterns. The flows are highly three-dimensional and chaotic in which the details vary from cycle to cycle. The flow patterns include internal jets, three-dimensional shear layers, stagnation lines, separation zones and recirculation zones. The vorticity and streamline maps confirm the highly complex and three-dimensional nature of the flow. WSS are estimated to range from -7 Pa to 30 Pa at the stenotic neck over time. Companion experiments are also carried out with sinusoidal and steady CCA input flows for comparison.

  9. [Experimental syringomyelia in rabbits and rats after localized spinal arachnoiditis].

    PubMed

    Tatara, N

    1992-12-01

    In order to produce syringomyelia, localized arachnoiditis was created in adult New Zealand albino rabbits and Wistar rats by the injection of kaolin into the thoracic spinal subarachnoid space and incision of the dura mater of the thoracic spinal cord. The rabbits and rats were divided into 3 groups; the control group, dural incision group (DG) and kaolin injection group (KG). Each rabbit was sacrificed at 4, 8, 12 and 16 weeks after the operation. Each rat was sacrificed at 8 and 16 weeks after the operation. Cavity formation in the cord of all rabbits was examined by ultrasound. All animals were perfused with 10% neutral beffered formalin at 150 cm H2O pressure, and histological examination was performed with Luxol fast blue (LFB) and hematoxylin and eosin (H&E) stains. Results obtained: (1) Cavity formation was noted in 6 of 16 DG of rabbit (37.5%), 5 of 16 KG of rabbit (31.2%) and 2 of 9 KG of rat (22.2%) with histological verification. With use of ultrasound, cavity was noted in 3 of 16 DG rabbits (12.5%) and 2 of 16 KG rabbits (18.8%). (2) Cavity formation was present in the cord adjacent to the marked adhesive arachnoiditis both in rabbits and in rats. (3) Cavity was noted in the ischemic area. (4) In 2 rabbits in which kaolin encircled whole surface of the spinal cord, hydromyelia was formed communicating with enlarged central canal caudad from the kaolin subarachnoid block. (5) Histological examination showed obliteration or narrowing of lumen of the small pial vessels involved in the adhesive arachnoiditis. In the cord parenchyma adjacent to the arachnoiditis, multiple spots of demyelination due secondary to ischemia demonstrated by LFB stain were noted. On the other hand, in the cord with the pia-arachnoid remained uninvolved, no demyelination was observed. (6) Localized adhesive arachnoiditis consisted of proliferation of fibrous tissue, lymphocytic infiltration and obliterating processes of small pial vessels involved in it. These data suggest that

  10. Flagella-induced immunity against experimental cholera in adult rabbits.

    PubMed Central

    Yancey, R J; Willis, D L; Berry, L J

    1979-01-01

    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. PMID:478635

  11. THE REACTION OF STANDARD BREEDS OF RABBITS TO EXPERIMENTAL SYPHILIS.

    PubMed

    Rosahn, P D

    1933-05-31

    A comparative study was made of the character and severity of the infection produced by Tr. pallidum in groups of standard bred Havana, Dutch, English, Himalayan, and Rex rabbits. All known variables that might influence the course of the disease were common to the different breed groups. On the basis of certain clinical data selected as criteria for the determination of variations in the response to syphilitic infection, it was found that the Havana and Dutch animals were resistant while the English, Himalayan, and Rex rabbits were susceptible. From these results, it appears that breed, race, or family is a factor which significantly influences the response to infection with Tr. pallidum.

  12. [The inhibitory effects of antioxidant vitamins on serum oxLDL and experimental atherosclerosis of rabbits].

    PubMed

    Chen, D; Yang, T; Song, F; Ruan, G; Liu, S

    1997-12-01

    In order to study the inhibitory effects of antioxidant vitamins on serum (low oxidative density lipoproteins, oxLDL) and experimental atherosclerosis in rabbits, 20 rabbits were fed on cholesterol rich diet and antioxidant vitamins (vitamin E, vitamin C and beta carotene) for 12 weeks. oxLDL were tested by ELISA at the beginning of experiment and after 4 weeks 8 weeks. The results showed that supplement of antioxidant vitamins can decrease the oxLDL level significantly and inhibited development of atherosclerosis lesion around aorta in rabbits.

  13. Prevention of experimental autoimmune cardiomyopathy in rabbits by receptor blockers.

    PubMed

    Matsui, S; Fu, M L

    2001-01-01

    We investigated the effects of beta1-adrenoceptor blockade and M2-muscarinic receptor antagonist in rabbits which have developed dilated cardiomyopathy-like changes after immunization with the peptides from the second extracellular loop of human beta1-adrenoceptor (beta1-peptide) and M2-muscarinic receptor (M2-peptide). Ten rabbits, which were immunized with beta1-peptide once a month for one year, were treated with bisoprolol and 10 rabbits, which were immunized with M2-peptide, were treated with otenzepad. Although both groups treated with receptor blockade or antagonist showed an increased titer of anti-beta1-adrenoceptor or anti-M2-muscarinic receptor antibodies, myocardial damages were markedly less than those in beta1-peptide- or M2-peptide-immunized rabbits. This study indicates that anti-beta1-adrenoceptor and anti-M2-muscarinic receptor antibodies are of pathogenic importance in the development of human dilated cardiomyopathy, and that beta-adrenoceptor blockade, bisoprolol, and M2-muscarinic receptor antagonist, otenzepad, might be clinically useful for treatment of dilated cardiomyopathy.

  14. An Experimental Study on the Ultimate Strength of the Adventitia and Media of Human Atherosclerotic Carotid Arteries in Circumferential and Axial Directions

    PubMed Central

    Teng, Zhongzhao; Tang, Dalin; Zheng, Jie; Woodard, Pamela K.; Hoffman, Allen H.

    2009-01-01

    Atherosclerotic plaque may rupture without warning causing heart attack or stroke. Knowledge of the ultimate strength of human atherosclerotic tissues is essential for understanding the rupture mechanism and predicting cardiovascular events. Despite its great importance, experimental data on ultimate strength of human atherosclerotic carotid artery remains very sparse. This study determined the uniaxial tensile strength of human carotid artery sections containing type II and III lesions (AHA classifications). Axial and circumferential oriented adventitia, media and intact specimens (total=73) were prepared from 6 arteries. The ultimate strength in uniaxial tension was taken as the peak stress recorded when the specimen showed the first evidence of failure and the extensibility was taken as the stretch ratio at failure. The mean adventitia strength values calculated using the 1st Piola-Kirchoff stress were 1996±867kPa and 1802±703kPa in the axial and circumferential directions respectively, while the corresponding values for the media sections were 519±270kPa and 1230±533kPa. The intact specimens showed ultimate strengths similar to media in circumferential direction but were twice as strong as the media in the axial direction. Results also indicated that adventitia, media and intact specimens exhibited similar extensibility at failure, in both the axial and circumferential directions (stretch ratio 1.50 +/−0.22). These measurements of the material strength limits for human atherosclerotic carotid arteries could be useful in improving computational models that assess plaque vulnerability. PMID:19665126

  15. Effects of dietary flaxseed on atherosclerotic plaque regression.

    PubMed

    Francis, Andrew A; Deniset, Justin F; Austria, Jose A; LaValleé, Renee K; Maddaford, Graham G; Hedley, Thomas E; Dibrov, Elena; Pierce, Grant N

    2013-06-15

    Dietary flaxseed can retard the progression of atherosclerotic plaques. However, it remains unclear whether these antiatherogenic effects extend to plaque regression. In the present study, the therapeutic potential of dietary flaxseed on atherosclerotic plaque regression and vascular contractile function was evaluated using a novel rabbit model. Rabbits were randomly assigned to receive either a regular diet for 12 wk (group I) or a 1% cholesterol-supplemented diet for 4 wk followed by a regular diet for 8 wk (group II). The remaining experimental animals were treated as in group II but were fed for an additional 14 wk with either a regular diet (group III) or a 10% flaxseed-supplemented diet (group IV). Animals in group II showed clear evidence of plaque growth stabilization. Their vessels also exhibited significantly lower norepinephrine-induced contraction and an impaired relaxation response to acetylcholine compared with animals in group I. Dietary flaxseed supplementation resulted in a significant ≈40% reduction in plaque formation (P = 0.033). Animals in both groups II and III displayed improved contraction and endothelium-dependent vessel relaxation. Dietary flaxseed is a valuable strategy to accelerate the regression of atherosclerotic plaques; however, flaxseed intervention did not demonstrate a clear beneficial effect on the vessel contractile response and endothelium-dependent vasorelaxation.

  16. RADIOLOGICAL ANALYSIS OF EXPERIMENTAL DISC DEGENERATION IN RABBITS

    PubMed Central

    Vialle, Emiliano; Vialle, Luiz Roberto; Arruda, André de Oliveira; Riet, Ricardo Nascimento; Krieger, Antônio Bernardo de Queiroz

    2015-01-01

    Objective: To validate radiographic evaluation of a rabbit model for disc degeneration. Methods: Lumbar intervertebral discs of New Zealand rabbits were stabbed three times with a 18G needle at a limited depth of 5mm, through lateral approach. Serial radiographic images were taken on the early pre-and postoperative periods, and after four, eight and 12 weeks of the procedure, with subsequent analysis of disc height, osteophyte formation, endplate sclerosis, and presence of disc degeneration. The statistical analysis of data was validated by the Kappa coefficient, with a confidence interval (CI) of 95%. Results: A significant reduction of disc space was found on AP X-ray images after 12 postoperative weeks, with Kappa = 0.489 for CI 95% (0.25-0.72) with p < 0.001. X-ray signs of disc degeneration also presented Kappa = 0.63 for CI 95% (0.39-0.86) with p < 0.001. The remaining assessed criteria showed positive results, but with a lower Kappa value. Conclusion: The disc degeneration model using rabbits as proposed in this study was shown to be feasible, with positive X-ray correlation between pre- and postoperative images, validating the potential to induce disc degeneration in this animal model for future studies. PMID:27022512

  17. Experimental infections of rabbits with proliferative and latent stages of Besnoitia besnoiti.

    PubMed

    Liénard, Emmanuel; Pop, Loredana; Prevot, Françoise; Grisez, Christelle; Mallet, Virginie; Raymond-Letron, Isabelle; Bouhsira, Émilie; Franc, Michel; Jacquiet, Philippe

    2015-10-01

    Cattle besnoitiosis due to Besnoitia besnoiti is spreading across Europe and is responsible for severe economic losses in newly infected herds. Experimentally speaking, rabbits have been found to be susceptible to this parasite. The adaptation of B. besnoiti to rabbits may offer a new, easier and cheaper model of investigation for this disease. This study compared the virulence between tachyzoites and bradyzoites of B. besnoiti in rabbits. Eighteen New Zealand rabbits were allocated into three groups of six animals each. The rabbits from the control (group C), "tachyzoite" (group T) and "bradyzoite" (group B) groups were subcutaneously injected in the right flank with 66 μg of ovalbumin, 6.10(6) tachyzoites (125th passage on Vero cells) and 6.10(6) bradyzoites (collected from a natural infected cow) of B. besnoiti, respectively. Clinical follow-up and blood sampling for serological survey and qPCR were performed during 10 weeks until euthanasia. Molecular and immunohistochemistry examination was achieved on 25 samples of tissue per rabbit. Seroconversion occurred in group T without any clinical signs. Rabbits of group B exhibited a febrile condition (temperature above 40 °C from day 8 to day 11 following injection) with positive qPCR in blood. Cysts of B. besnoiti were found on skin samples and organs of rabbits from group B in tissue explored with threshold cycle (Ct) values below 30. These results suggest a higher virulence of bradyzoites in rabbits than Vero cell-cultivated tachyzoites. The proposed model could be used to assess the in vivo effectiveness of vaccine or drugs against cattle besnoitiosis.

  18. Immunization with viruslike particles from cottontail rabbit papillomavirus (CRPV) can protect against experimental CRPV infection.

    PubMed Central

    Breitburd, F; Kirnbauer, R; Hubbert, N L; Nonnenmacher, B; Trin-Dinh-Desmarquet, C; Orth, G; Schiller, J T; Lowy, D R

    1995-01-01

    We tested the ability of vaccination with virus-like particles (VLPs) to protect domestic rabbits against papillomas induced by the cottontail rabbit papillomavirus (CRPV). A recombinant baculovirus system that expressed only the L1 major papillomavirus structural protein or L1 plus the minor L2 protein was used in insect cells as the source of VLPs. Groups of 10 rabbits were immunized with native or denatured VLPs from CRPV or type 1 bovine papillomavirus by using Freund's adjuvant. Alum was used as the adjuvant for an additional group immunized with CRPV L1-L2 VLPs. Animals were challenged with 5 x 10(10) and 2 x 10(11) particles on opposing flanks. No protection was seen in rabbits immunized with native or denatured bovine papillomavirus L1-L2 or with denatured CRPV L1-L2. In these groups, the lower and higher challenge doses resulted in 27 of 30 animals with extensive papillomas, with each of the remaining animals having a smaller number of persistent papillomas. Progression to carcinoma developed in 20 rabbits. Animals inoculated with native CRPV VLPs composed of L1 alone or L1-L2 developed many fewer lesions; the lower and higher challenge doses resulted in 17 of 29 and 5 of 29 rabbits, respectively, with no lesions, and the remainder developed only one to eight papillomas, which all regressed except for those on 1 rabbit. None developed cancer within 1 year of infection. Rabbits vaccinated with native CRPV VLPs developed high-titer antibodies in an enzyme-linked immunosorbent assay based on native VLPs, and passive transfer of serum or immunoglobulin G from rabbits immunized with CRPV VLPs protected against CRPV challenge. We conclude that native VLPs can induce antibody-mediated, type-specific protection against experimental papillomavirus infection. PMID:7745754

  19. Immunization with viruslike particles from cottontail rabbit papillomavirus (CRPV) can protect against experimental CRPV infection.

    PubMed

    Breitburd, F; Kirnbauer, R; Hubbert, N L; Nonnenmacher, B; Trin-Dinh-Desmarquet, C; Orth, G; Schiller, J T; Lowy, D R

    1995-06-01

    We tested the ability of vaccination with virus-like particles (VLPs) to protect domestic rabbits against papillomas induced by the cottontail rabbit papillomavirus (CRPV). A recombinant baculovirus system that expressed only the L1 major papillomavirus structural protein or L1 plus the minor L2 protein was used in insect cells as the source of VLPs. Groups of 10 rabbits were immunized with native or denatured VLPs from CRPV or type 1 bovine papillomavirus by using Freund's adjuvant. Alum was used as the adjuvant for an additional group immunized with CRPV L1-L2 VLPs. Animals were challenged with 5 x 10(10) and 2 x 10(11) particles on opposing flanks. No protection was seen in rabbits immunized with native or denatured bovine papillomavirus L1-L2 or with denatured CRPV L1-L2. In these groups, the lower and higher challenge doses resulted in 27 of 30 animals with extensive papillomas, with each of the remaining animals having a smaller number of persistent papillomas. Progression to carcinoma developed in 20 rabbits. Animals inoculated with native CRPV VLPs composed of L1 alone or L1-L2 developed many fewer lesions; the lower and higher challenge doses resulted in 17 of 29 and 5 of 29 rabbits, respectively, with no lesions, and the remainder developed only one to eight papillomas, which all regressed except for those on 1 rabbit. None developed cancer within 1 year of infection. Rabbits vaccinated with native CRPV VLPs developed high-titer antibodies in an enzyme-linked immunosorbent assay based on native VLPs, and passive transfer of serum or immunoglobulin G from rabbits immunized with CRPV VLPs protected against CRPV challenge. We conclude that native VLPs can induce antibody-mediated, type-specific protection against experimental papillomavirus infection.

  20. Renal injury is a consistent finding in Dutch Belted rabbits experimentally infected with enterohemorrhagic Escherichia coli.

    PubMed

    Garcia, Alexis; Bosques, Carlos J; Wishnok, John S; Feng, Yan; Karalius, Brad J; Butterton, Joan R; Schauer, David B; Rogers, Arlin B; Fox, James G

    2006-04-15

    Enterohemorrhagic Escherichia coli (EHEC) produces Shiga toxin (Stx) and causes renal disease in humans. Dutch Belted (DB) rabbits naturally infected with EHEC O153 develop hemolytic-uremic syndrome-like disease. The aims of this study were to experimentally reproduce O153-induced renal disease in DB rabbits and investigate bacterial and host factors involved in pathogenesis. The pathogenicity of E. coli O157:H7 was also investigated in rabbits. The stx1AB region of O153 was sequenced. By use of liquid chromatography-tandem mass spectrometry, we identified homologs of the Stx receptor, globotriaosylceramide (Gb3), in rabbit kidney extracts. Infected rabbits developed clinical signs and intestinal and kidney lesions. Renal pathological changes consisted of intimal swelling, perivascular edema, erythrocyte fragmentation, capillary thickening, luminal constriction, leukocytic infiltration, mesangial deposits, and changes in Bowman's capsule and space. Sequence analysis of a approximately 7-kb region of the O153 chromosome indicated homology to the Stx1-producing bacteriophage H19B. Our findings indicate that DB rabbits are suitable for the study of the renal manifestations of EHEC infection in humans.

  1. Experimental acute pancreatitis induced by platelet activating factor in rabbits.

    PubMed Central

    Emanuelli, G.; Montrucchio, G.; Gaia, E.; Dughera, L.; Corvetti, G.; Gubetta, L.

    1989-01-01

    This study indicates that a single injection of platelet activating factor (PAF, 50-500 ng) into the superior pancreaticoduodenal artery of rabbits induces dose-dependent morphologic alterations of pancreatic tissue and increases serum amylase levels, both consistent with the development of an acute pancreatitis. The main histologic findings observed by light microscopy 24-72 hours after the injection of PAF were edema, polymorphonuclear neutrophil infiltration, cell vacuolization, and acinar cell necrosis. Fat cell necrosis was present in 30% of animals. By electron microscopy an increase of the number of zymogen granules in the apical region of acinar cells was observed 3 hours after PAF challenge. At 24-72 hours, many acinar cells showed vacuoles containing myelinlike figures, zymogen granules, and cellular debris. Pancreatic lesions developed in the area supplied by the artery injected with PAF and they were completely antagonized by the pretreatment of rabbits with CV 3988, a specific antagonist of PAF. In addition, the significant protective effect of atropine suggests a potential role for cholinergic mechanisms in the pancreatic alterations induced by PAF. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:2464939

  2. A new minimally invasive experimental spinal cord injury model in rabbits.

    PubMed

    Baydin, A; Cokluk, C; Aydin, K

    2007-06-01

    The aim of this experimental study was to evaluate the effectivity of epidural microballoon inflation into the unroofed spinal column for the creation of a new experimental spinal cord injury model in rabbits. 10 New Zealand white rabbits were used for this study. Before operation and after anasthesia with 50 mg/kg ketamine and 8 mg/kg xylazine, spinal evoked potentials (SEP) were recorded in all rabbits. A midline skin incision was done on the lomber skin at the level of L1-L4. Paravertebral muscles were dissected bilaterally. A microhemilaminotomy was done in the right L3 lamina close to the midline by using Midas-rex micro-diamond drill instruments. The ligamentum flavum was opened and removed with microscissors. A microballoon was inserted into the spinal column between the bone and dura mater to the level of T12. The microballoon was inflated by using a pressure- and volume-controlled microballoon inflation device. Pre-injury and post-injury SEPs were recorded. The microballoon was deflated 15 minutes later and removed completely from the epidural space. 24 hours later the SEP study was repeated. Following microballoon inflation the SEP waves dropped to the basal level. All rabbits were paraplegic after the operation. In conclusion, this experimental study demonstrated that the microballoon inflation technique is a very successful method for the evaluation of spinal cord injury in rabbits. Unroofing of the spinal column is extremely important because decompression may be an effective treatment in spinal cord injury. Also the traumatic effect of aneurysm clips represents a different type of injury to the spinal cord. This new model may be used in experimental studies of spinal cord injury in rabbits.

  3. [Autologous grafting of extraocular muscles: experimental study in rabbits].

    PubMed

    Meireles-Teixeira, Jorge; Bicas, Harley E A

    2005-01-01

    To evaluate the feasibility of autologous extraocular muscle grafting as a type of muscle expansion surgery. The left superior rectus muscle of twenty-nine rabbits was resected and this fragment was attached to the endpoint of the respective right superior rectus (test group). Thereafter, the superior rectus of the left eye was reattached to the sclera (control group). Both groups were examined during different postoperative periods in order to assess their outcomes. The presence of hyperemia was slightly more frequent in the grafted group. Secretion and muscle atrophy were negligible in both groups. Fibrosis was greater in grafted animals. These muscles were weaker than the control muscles, although the force required to split muscular parts was always greater than the physiological one. This surgical technique was reliable and useful if one intends to achieve muscle expansion without the intrinsic risks of dealing with heterologous/artificial materials.

  4. Experimental investigations in hamsters and rabbits with DNA extracted from human uterine tumors.

    PubMed

    Nastac, E; Athanasiu, P; Predescu, E; Stoian, M; Hozoc, M; Perju, A

    1980-01-01

    Experimental inoculation of a DNA preparation extracted from a fragment of non-irradiated human uterine cervix carcinoma was followed by the appearance of neoplasia in four hamsters and of lymphosarcoma in one rabbit. Similar DNA preparations obtained from three cases of irradiated human uterine cervix carcinoma and from a human uterine fibroma proved to have no biological activity.

  5. Experimental coronary sclerosis induced by immobilization of rabbits: A new model of arteriosclerosis

    NASA Technical Reports Server (NTRS)

    Tyavokin, V. V.; Tjawokin, W. W.

    1980-01-01

    A new method for producing arteriosclerosis with coronary insufficiency in rabbits by means of immobilization is described and discussed. The experimentally induced atherosclerosis develops due to hypodynamics imposed by the reduced muscular activity without overloading with exogenous cholesterol. The atherosclerosis and coronary insufficiency are associated. With variations in the duration and extent of immobilization, coronary insufficiency alone or with atherosclerosis can be produced.

  6. Quantification of HTLV-I proviral load in experimentally infected rabbits.

    PubMed

    Zhao, Tong-Mao; Hague, Bishop; Caudell, David L; Simpson, R Mark; Kindt, Thomas J

    2005-05-23

    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. 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. 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.

  7. Primary and secondary experimental infestation of rabbits (Oryctolagus cuniculus) with Sarcoptes scabiei from a wild rabbit: factors determining resistance to reinfestation.

    PubMed

    Casais, Rosa; Dalton, Kevin P; Millán, Javier; Balseiro, Ana; Oleaga, Alvaro; Solano, Paloma; Goyache, Félix; Prieto, José Miguel; Parra, Francisco

    2014-06-16

    Studies of sarcoptic mange and immunity are hampered by lack of mite sources and natural infestation models. We have investigated the clinical and pathological signs, specific IgG response and acquired immunity in naïve New Zealand White rabbits (Oryctolagus cuniculus) experimentally infested with Sarcoptes scabiei originally isolated from a clinically affected free-living European wild rabbit. Twenty rabbits were infested using two methods, direct contact for a 24 h period with a seeder rabbit simulating the natural process of infestation and application of a dressing holding approximately 1800 live mites on each hind limb (foot area) for a 24h period. Eight weeks post infestation, rabbits were treated with ivermectin and infestation cleared. Eight weeks later seventeen previously infested and four uninfested naïve controls were then re-exposed to the same S. scabiei variety using the same methods and followed for another 8 weeks. The progress of the disease was markedly more virulent in the animals infested by contact, indicating that the effective dose of mites managing to thrive and infest each rabbit by this method was higher. Nevertheless, infestation by contact resulted in partial protection to reexposure, rabbits developed high non-protective antibody titres upon reinfestation and presented severe clinical signs. However, rabbits reinfested by dressing developed lower IgG titres, and presented high levels of resistance to reinfestation, which might be due to induction of a strong local cellular response in the inoculation point that killed the mites and resulted in a lower mite effective dose, with subsequent reduced lesion development. Statistical analysis showed that sex, method of infestation and previous exposure are key factors determining the ability of rabbits to develop immunity to this disease. The rabbit-mange model developed will allow the further study of immunity and resistance to this neglected pathogen using a natural host system.

  8. Experimental infection of rabbits with bovine viral diarrhoea virus by a natural route of exposure

    PubMed Central

    2014-01-01

    Bovine viral diarrhoea virus (BVDV) is an important pathogen of cattle that can naturally infect a wide range of even-toed ungulates. Non-bovine hosts may represent reservoirs for the virus that have the potential to hamper BVDV eradication programs usually focused on cattle. Rabbits are very abundant in countries such as the United Kingdom or Australia and are often living on or near livestock pastures. Earlier reports indicated that rabbits can propagate BVDV upon intravenous exposure and that natural infection of rabbits with BVDV may occur but experimental proof of infection of rabbits by a natural route is lacking. Therefore, New Zealand White rabbits were exposed to a Scottish BVDV field strain intravenously, oro-nasally and by contaminating their hay with virus. None of the animals showed any clinical signs. However, the lymphoid organs from animals sacrificed at day five after exposure showed histological changes typical of transient infection with pestivirus. Most organ samples and some buffy coat samples were virus positive at day five but saliva samples remained negative. Development of antibodies was observed in all intravenously challenged animals, in all of the nebulised group and in four of six animals exposed to contaminated hay. To our knowledge this is the first report of BVDV propagation in a species other than ruminants or pigs after exposure to the virus by a natural route. However, to assess the role of rabbits as a potential reservoir for BVDV it remains to be determined whether persistent infection caused by intra-uterine infection is possible and whether BVDV is circulating in wild rabbit populations. PMID:24690167

  9. Preparation of platelet-rich plasma as a tissue adhesive for experimental transplantation in rabbits

    PubMed Central

    Luengo Gimeno, Federico; Gatto, Silvia; Ferro, José; Croxatto, Juan Oscar; Gallo, Juan Eduardo

    2006-01-01

    Purpose Platelet-rich plasma (PRP) is an autologous substance with adhesive properties. We aimed at developing and testing the efficacy of a method for PRP preparation in rabbits. Materials and methods An in vitro study was carried out to obtain PRP from forty rabbits and to analyze the number of platelets and type of substance needed to trigger platelet activation. To induce platelet activation, 5%, 10%, 25% and 50% CaCl solutions were used. Then, an in vivo study was performed in twelve rabbits to test PRP adhesiveness in lamellar corneal graft. A control group made up of six rabbits underwent corneal transplantation without using PRP. Results 5% CaCl was the most effective concentration in activating PRP, with a mean time of 19 minutes. An attached corneal flap was seen 3 months after surgery. A detached corneal button was seen in all controls. Conclusion Our method was able to produce rabbit-derived PRP with suitable properties for soft tissue adhesion. These results could be useful for researchers of the growing fields of tissue repair and experimental transplantation. PMID:17005053

  10. EXPERIMENTAL OBSERVATIONS ON THE "CURE" OF SYPHILIS IN THE RABBIT WITH ARSPHENAMINE

    PubMed Central

    Chesney, Alan M.; Kemp, Jarold E.

    1924-01-01

    1. The intravenous administration of six doses of arsphenamine to syphilitic rabbits in amounts of 10 mg. per kilo, 127 days after inoculation is sufficient to render the popliteal nodes of such animals incapable of transmitting the infection to normal animals. 2. Syphilitic rabbits that have been treated in this manner and whose popliteal nodes 32 to 38 days after treatment have been shown to be incapable of transmitting the infection to normal animals are, as far as can be judged by the absence of a local lesion, refractory to a second inoculation of active virus of the same strain, if the inoculation be made intradermally at the base of the ear and carried out 209 days after the first inoculation. 3. Untreated syphilitic rabbits are also refractory toward a second inoculation made in a similar manner and at a similar interval following the first inoculation. 4. Evidence is offered in favor of the view that the most satisfactory method of evaluation of antisyphilitic agents in experimental syphilis of the rabbit is that of lymph node transfer. 5. Evidence is offered in support of the view that the state of refractoriness toward a second inoculation exhibited by syphilitic rabbits may be explainable upon the basis of either an acquired immunity or persistence of a focus of living treponemata in the body. PMID:19868865

  11. EXPERIMENTAL OBSERVATIONS ON THE "CURE" OF SYPHILIS IN THE RABBIT WITH ARSPHENAMINE.

    PubMed

    Chesney, A M; Kemp, J E

    1924-03-31

    1. The intravenous administration of six doses of arsphenamine to syphilitic rabbits in amounts of 10 mg. per kilo, 127 days after inoculation is sufficient to render the popliteal nodes of such animals incapable of transmitting the infection to normal animals. 2. Syphilitic rabbits that have been treated in this manner and whose popliteal nodes 32 to 38 days after treatment have been shown to be incapable of transmitting the infection to normal animals are, as far as can be judged by the absence of a local lesion, refractory to a second inoculation of active virus of the same strain, if the inoculation be made intradermally at the base of the ear and carried out 209 days after the first inoculation. 3. Untreated syphilitic rabbits are also refractory toward a second inoculation made in a similar manner and at a similar interval following the first inoculation. 4. Evidence is offered in favor of the view that the most satisfactory method of evaluation of antisyphilitic agents in experimental syphilis of the rabbit is that of lymph node transfer. 5. Evidence is offered in support of the view that the state of refractoriness toward a second inoculation exhibited by syphilitic rabbits may be explainable upon the basis of either an acquired immunity or persistence of a focus of living treponemata in the body.

  12. Differential effect of Pistacia vera extracts on experimental atherosclerosis in the rabbit animal model: an experimental study

    PubMed Central

    2010-01-01

    Background Lipid-enriched diets and oxidative stress are risk factors for the development of atherosclerosis. The effects of the methanolic (ME) and cyclohexane (CHE) extracts of the Pistacia vera nut, often included in the Mediterranean diet, were studied in the rabbit model of atherosclerosis. Methods and results Twenty-four New Zealand White rabbits received atherogenic diet (Control Group), supplemented with ME (Group ME) or CHE (Group CHE) for 3 months. Previously, a GC-MS and a UHPLC LC-DAD-ESI(-)-HRMS/MS method were developed to investigate the extracts' chemical profiles. Blood samples at baseline and monthly determined lipid profile, lipid peroxidation and liver function. The aorta, myocardium and liver were examined histologically at 3 months. Groups ME and CHE had significantly higher HDL- and non-significantly lower LDL-cholesterol median % changes from baseline than the Control Group. Triacylglycerol was significantly higher in Group CHE vs. Control. MDA values were significantly lower in Group ME vs. Control and CHE. ALT and AST were significantly higher in Group CHE vs. Control. γ-GT was lower in Group ME vs. Control. Aortic intimal thickness was significantly less in Groups ME and CHE vs. Control; Group ME atherosclerotic lesions were significantly less extensive vs. Groups Control and CHE. Only Group CHE had significant liver fatty infiltration. Conclusions During short-term administration concomitantly with atherogenic diet, both P. vera extracts were beneficial on HDL-, LDL-cholesterol and aortic intimal thickness. The ME additionally presented an antioxidant effect and significant decrease of aortic surface lesions. These results indicate that P. vera dietary inclusion, in particular its ME, is potentially beneficial in atherosclerosis management. PMID:20633299

  13. Respiratory and neurological disease in rabbits experimentally infected with equid herpesvirus 1.

    PubMed

    Kanitz, Fábio A; Cargnelutti, Juliana F; Anziliero, Deniz; Gonçalves, Kelley V; Masuda, Eduardo K; Weiblen, Rudi; Flores, Eduardo F

    2015-10-01

    Equid herpesvirus type 1 (EHV-1) is an important pathogen of horses worldwide, associated with respiratory, reproductive and/or neurological disease. A mouse model for EHV-1 infection has been established but fails to reproduce some important aspects of the viral pathogenesis. Then, we investigated the susceptibility of rabbits to EHV-1 aiming at proposing this species as an alternative model for EHV-1 infection. Weanling rabbits inoculated intranasal with EHV-1 Kentucky D (10(7) TCID50/animal) shed virus in nasal secretions up to day 8-10 post-inoculation (pi), presented viremia up to day 14 pi and seroconverted to EHV-1 (virus neutralizing titers 4 to 64). Most rabbits (75%) developed respiratory disease, characterized by serous to hemorrhagic nasal discharge and mild to severe dyspnea. Some animals (20%) presented neurological signs as circling, bruxism and opisthotonus. Six animals died during acute disease (days 3-6); infectious virus and/or viral DNA were detected in the lungs, trigeminal ganglia (TG), olfactory bulbs (OBs) and cerebral cortex/brain (CC). Histological examination showed necrohemorrhagic, multifocal to coalescent bronchointerstitial pneumonia and diffuse alveolar edema. In two rabbits euthanized at day 50 pi, latent EHV-1 DNA was detected in the OBs. Dexamethasone administration at day 50 pi resulted in virus reactivation, demonstrated by virus shedding, viremia, clinical signs, and increase in VN titers and/or by detection of virus DNA in lungs, OBs, TGs and/or CC. These results demonstrate that rabbits are susceptible to EHV-1 infection and develop respiratory and neurological signs upon experimental inoculation. Thus, rabbits may be used to study selected aspects of EHV-1 biology and pathogenesis, extending and complementing the mouse model.

  14. Use of Ligated Segments of Rabbit Small Intestine in Experimental Shigellosis1

    PubMed Central

    Arm, H. G.; Floyd, T. M.; Faber, J. E.; Hayes, J. R.

    1965-01-01

    Arm, H. G. (Naval Medical Research Institute, Bethesda, Md.), T. M. Floyd, J. E. Faber, and J. R. Hayes. Use of ligated segments of rabbit small intestine in experimental shigellosis. J. Bacteriol. 89:803–809. 1965.—Inoculation of ligated segments of small intestine in living rabbits with broth cultures or resting-cell suspensions of recently isolated strains of Shigella caused distension of the segments by accumulation of exudate within 12 hr. Histological changes characteristic of an inflammatory response were similar to those of human bacillary dysentery. Tissue response and accumulation of exudate preceded demonstrable increase in numbers of shigellae inoculated as 2 × 1010 resting cells. Capability of shigellae to provoke intestinal response was not related to any particular serological group. The active principles concerned with eliciting intestinal response were associated only with preparations containing living organisms. Ability of recently isolated strains to elicit response diminished rapidly during culture on artificial media. The capability was preserved indefinitely by lyophilization soon after isolation from acute bacillary dysentery infections of man. Advantages of using shigellae recently isolated for investigating possible mechanisms of pathogenesis were indicated. During the summer months, the rabbit small intestine was refractory to the activity of shigellae, and positive responses were not observed. Use of ligated segments of rabbit small intestine qualified as an indicator of virulence for the rabbit; and, virulence for the rabbit showed a high degree of correlation with a short period of culture of shigellae on artificial media after isolation from human bacillary dysentery infections. Images PMID:14273664

  15. THE EFFECT OF CORTISONE ON THE SERUM LIPIDS AND ON THE DEVELOPMENT OF EXPERIMENTAL CHOLESTEROL ATHEROSCLEROSIS IN THE RABBIT

    PubMed Central

    Gordon, Dina; Kobernick, Sidney D.; McMillan, Gardner C.; Duff, G. Lyman

    1954-01-01

    An experiment was performed to determine the effect of cortisone on the serum lipids and on the development of experimental cholesterol atherosclerosis in the rabbit. Litter mate rabbits of the same sex were employed; both sexes were represented in the experiment. The report is based upon four experimental groups comprising (1) 12 rabbits fed cholesterol and treated with cortisone vehicle; (2) 12 rabbits fed cholesterol and treated daily with cortisone; (3) 11 rabbits treated with cortisone; and (4) 7 rabbits that received cortisone vehicle. It was observed that: (1) There was less aortic atherosclerosis in the cholesterol-fed cortisone-treated rabbits as judged by both morphological and chemical means than in the rabbits fed cholesterol without cortisone treatment. (2) Cortisone depressed appreciably the hypercholesterolemia resulting from the feeding of cholesterol to rabbits. (3) Cortisone treatment caused a moderate hypercholesterolemia in normal rabbits. (4) Cortisone caused a moderate increase in serum lipid phosphorus equal to that produced by cholesterol feeding alone. (5) The combination of cholesterol feeding and cortisone did not result in a higher phospholipidemia than either one of these agents alone. (6) Cortisone caused a great increase in serum-neutral fat; it was not apparent whether cholesterol feeding affected the neutral fat lipemia due to cortisone treatment alone. (7) The total cholesterol to lipid phosphorus ratio was about normal in the rabbits that received cortisone only. It was doubled in the animals receiving both cholesterol and cortisone, and it was increased about four times in those that received only cholesterol. The significance of the alterations in the serum lipids induced by cortisone is discussed in relation to the inhibition of the development of aortic atherosclerosis that occurred in the cholesterol-fed rabbits treated with cortisone. PMID:13152282

  16. Nuclear microscopy of atherosclerotic tissue

    NASA Astrophysics Data System (ADS)

    Watt, F.; Selley, M.; Thong, P. S. P.; Tang, S. M.

    1995-09-01

    Of the many proposed coronary disease risk factors, the link between heart disease and stored iron has been the subject of recent interest. Samples of proximal thoracic aorta were taken from rabbits fed with 1% cholesterol for 12 weeks, and also from control animals. Unstained freeze dried sections were scanned using the nuclear microscope at the National University of Singapore (NUS) and results indicate that there is an eightfold increase in iron (from 12 ppm to 90 ppm) within the atherosclerotic lesion compared with normal tissue. This result adds weight to the theory that iron may act as a factor in the oxidative modification of low-density lipoprotein (LDL), which induces the formation of foam cells, characteristic of early atherosclerotic lesions.

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

    PubMed

    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.

  18. Anti-hypercholesterolemic and anti-atherosclerotic effects of polarized-light therapy in rabbits fed a high-cholesterol diet.

    PubMed

    Park, Dongsun; Kyung, Jangbeen; Kim, Dajeong; Hwang, Seock-Yeon; Choi, Ehn-Kyoung; Kim, Yun-Bae

    2012-03-01

    The effects of polarized-light therapy (PLT) on high-cholesterol diet (HCD)-induced hypercholesterolemia and atherosclerosis were investigated in comparison with that of lovastatin in rabbits. Hypercholesterolemia was induced by feeding male New Zealand white rabbits with 1% cholesterol in diet for 2 weeks and maintained with 0.5% cholesterol for 6 weeks, followed by normal diet for 2 weeks for recovery. Lovastatin (0.002% in diet) or daily 5-min or 20-min PLT on the outside surface of ears was started 2 weeks after induction of hypercholesterolemia. Hypercholesterolemic rabbits exhibited great increases in serum cholesterol and low-density lipoproteins (LDL) levels, and finally severe atheromatous plaques formation covering 57.5% of the arterial walls. Lovastatin markedly reduced both the cholesterol and LDL, but the reducing effect (47.5%) on atheroma formation was relatively low. By comparison, 5-min PLT preferentially decreased LDL, rather than cholesterol, and thereby potentially reduced the atheroma area to 42.2%. Notably, 20-min PLT was superior to lovastatin in reducing both the cholesterol and LDL levels as well as the atheromatous plaque formation (26.4%). In contrast to the increases in blood alanine transaminase and aspartate transaminase following lovastatin treatment, PLT did not cause hepatotoxicity. In addition, PLT decreased platelets and hematocrit level. The results indicate that PLT attenuates atherosclerosis not only by lowering blood cholesterol and LDL levels, but also by improving blood flow without adverse effects. Therefore, it is suggested that PLT could be a safe alternative therapy for the improvement of hypercholesterolemia and atherosclerosis.

  19. Anti-hypercholesterolemic and anti-atherosclerotic effects of polarized-light therapy in rabbits fed a high-cholesterol diet

    PubMed Central

    Park, Dongsun; Kyung, Jangbeen; Kim, Dajeong; Hwang, Seock-Yeon; Choi, Ehn-Kyoung

    2012-01-01

    The effects of polarized-light therapy (PLT) on high-cholesterol diet (HCD)-induced hypercholesterolemia and atherosclerosis were investigated in comparison with that of lovastatin in rabbits. Hypercholesterolemia was induced by feeding male New Zealand white rabbits with 1% cholesterol in diet for 2 weeks and maintained with 0.5% cholesterol for 6 weeks, followed by normal diet for 2 weeks for recovery. Lovastatin (0.002% in diet) or daily 5-min or 20-min PLT on the outside surface of ears was started 2 weeks after induction of hypercholesterolemia. Hypercholesterolemic rabbits exhibited great increases in serum cholesterol and low-density lipoproteins (LDL) levels, and finally severe atheromatous plaques formation covering 57.5% of the arterial walls. Lovastatin markedly reduced both the cholesterol and LDL, but the reducing effect (47.5%) on atheroma formation was relatively low. By comparison, 5-min PLT preferentially decreased LDL, rather than cholesterol, and thereby potentially reduced the atheroma area to 42.2%. Notably, 20-min PLT was superior to lovastatin in reducing both the cholesterol and LDL levels as well as the atheromatous plaque formation (26.4%). In contrast to the increases in blood alanine transaminase and aspartate transaminase following lovastatin treatment, PLT did not cause hepatotoxicity. In addition, PLT decreased platelets and hematocrit level. The results indicate that PLT attenuates atherosclerosis not only by lowering blood cholesterol and LDL levels, but also by improving blood flow without adverse effects. Therefore, it is suggested that PLT could be a safe alternative therapy for the improvement of hypercholesterolemia and atherosclerosis. PMID:22474473

  20. Imaging the Cytokine Receptor CXCR4 in Atherosclerotic Plaques with the Radiotracer (68)Ga-Pentixafor for PET.

    PubMed

    Hyafil, Fabien; Pelisek, Jaroslav; Laitinen, Iina; Schottelius, Margret; Mohring, Miriam; Döring, Yvonne; van der Vorst, Emiel P C; Kallmayer, Michael; Steiger, Katja; Poschenrieder, Andreas; Notni, Johannes; Fischer, Johannes; Baumgartner, Christine; Rischpler, Christoph; Nekolla, Stephan G; Weber, Christian; Eckstein, Hans-Henning; Wester, Hans-Jürgen; Schwaiger, Markus

    2017-03-01

    (68)Ga-pentixafor is a radiotracer for PET that binds with nanomolar affinity to CXCR4. The CXCR4 receptor is expressed at the surface of inflammatory cells. The objective of the study was to analyze the ability of radiolabeled pentixafor to detect CXCR4 expression on inflammatory cells present in atherosclerotic plaques of an experimental rabbit model. Methods: Atherosclerotic plaques were induced by endothelial abrasion of the right carotid artery and abdominal aorta of 7 rabbits fed an atherogenic diet. Five noninjured rabbits fed a chow diet were used as controls. Rabbits were imaged on a PET/MR system after injection of (68)Ga-pentixafor (15 MBq/kg). Vascular signal was quantified as tissue-to-background ratio (TBR). Biodistribution and autoradiographic studies were performed 1 h after injection of (125)I-pentixafor (7.5 MBq/kg). In addition, blocking studies were performed in 2 atherosclerotic rabbits with preinjection of the CXCR4 inhibitor AMD3100. Tracer uptake was quantified on arterial cryosections using autoradiography and compared with CXCR4 and RAM-11 (macrophage) expression on adjacent histologic sections. Results: One hour after injection of (68)Ga-pentixafor, strong signals were detected in vivo with PET/MR imaging in atherosclerotic plaques of the abdominal aorta and right carotid artery as compared with normal control arteries (mean TBR = 1.95 ± 0.51 vs. 1.22 ± 0.25 and mean TBR = 1.24 ± 0.38 vs. 0.96 ± 0.37, respectively; P < 0.05 for both). Blocking studies with preinjection of a CXCR4 inhibitor reduced (125)I-pentixafor uptake in atherosclerotic plaques by approximately 40%. (125)I-pentixafor uptake in the vessel wall on autoradiographies was located in macrophage-rich regions of atherosclerotic plaques and correlated with the intensity of CXCR4 expression on corresponding cryosections (r(2) = 0.61; P < 0.05). Conclusion:(68)Ga-pentixafor allows for the noninvasive detection of CXCR4 expression in the vessel wall with PET and emerges as a

  1. Rabbit retinal neovascularization induced by latex angiogenic-derived fraction: an experimental model.

    PubMed

    Sampaio, R B; Mendonca, R J; Simioni, A R; Costa, R A; Siqueira, R C; Correa, V M; Tedesco, A C; Haddad, A; Coutinho Netto, J; Jorge, R

    2010-01-01

    To create a retinal neovascularization experimental model using intravitreal injection of microspheres loaded with latex-derived angiogenic fraction. Thirty-two albino New Zealand rabbits, divided in 4 groups of 8 animals, were enrolled in this study. Rabbits in groups I, II, and III received one intravitreal injection of PLGA (L-lactide-co-glycolide) microspheres with 10, 30, and 50 microg of latex-derived angiogenic fraction into their right eyes, respectively, and group IV received 0.1 ml of microspheres without the angiogenic fraction. Weekly follow-up with ophthalmoscopy and fluorescein angiography was performed; the rabbits were sacrificed in the 4th week and their eyes processed for light microscopy. All eyes from group I demonstrated increased retinal vascular tortuosity, observed from 14 days after injection and maintained for 28 days, otherwise without new vessels detection. All group II eyes showed vascular changes similar to group I. Fifty percent of the eyes from group II rabbits developed retinal neovascularization 21 days after injection. All eyes from group III demonstrated significant vascular tortuosity and retinal new vessels 2 weeks after injection, progressing to fibrovascular proliferation and tractional retinal detachment. No vascular changes or retinal new vessels were observed in group IV eyes. Light microscopy confirmed the existence of new vessels previously seen on fluorescein angiography, in retinal sections adjacent to the optic disc, not observed in sections at the same area in the control group. Thirty- and 50-microg microspheres containing latex-derived angiogenic fraction injected into the vitreous cavity induced retinal neovascularization in rabbits.

  2. An in vivo system for directed experimental evolution of rabbit haemorrhagic disease virus

    PubMed Central

    Hall, Robyn N.; Capucci, Lorenzo; Matthaei, Markus; Esposito, Simona; Kerr, Peter J.; Frese, Michael; Strive, Tanja

    2017-01-01

    The calicivirus Rabbit haemorrhagic disease virus (RHDV) is widely used in Australia as a biocontrol agent to manage wild European rabbit (Oryctolagus cuniculus) populations. However, widespread herd immunity limits the effectiveness of the currently used strain, CAPM V-351. To overcome this, we developed an experimental platform for the selection and characterisation of novel RHDV strains. As RHDV does not replicate in cell culture, variant viruses were selected by serially passaging a highly virulent RHDV field isolate in immunologically naïve laboratory rabbits that were passively immunised 18–24 hours post-challenge with a neutralising monoclonal antibody. After seven passages, two amino acid substitutions in the P2 domain of the capsid protein became fixed within the virus population. Furthermore, a synonymous substitution within the coding sequence of the viral polymerase appeared and was also maintained in all subsequent passages. These findings demonstrate proof-of-concept that RHDV evolution can be experimentally manipulated to select for virus variants with altered phenotypes, in this case partial immune escape. PMID:28288206

  3. An in vivo system for directed experimental evolution of rabbit haemorrhagic disease virus.

    PubMed

    Hall, Robyn N; Capucci, Lorenzo; Matthaei, Markus; Esposito, Simona; Kerr, Peter J; Frese, Michael; Strive, Tanja

    2017-01-01

    The calicivirus Rabbit haemorrhagic disease virus (RHDV) is widely used in Australia as a biocontrol agent to manage wild European rabbit (Oryctolagus cuniculus) populations. However, widespread herd immunity limits the effectiveness of the currently used strain, CAPM V-351. To overcome this, we developed an experimental platform for the selection and characterisation of novel RHDV strains. As RHDV does not replicate in cell culture, variant viruses were selected by serially passaging a highly virulent RHDV field isolate in immunologically naïve laboratory rabbits that were passively immunised 18-24 hours post-challenge with a neutralising monoclonal antibody. After seven passages, two amino acid substitutions in the P2 domain of the capsid protein became fixed within the virus population. Furthermore, a synonymous substitution within the coding sequence of the viral polymerase appeared and was also maintained in all subsequent passages. These findings demonstrate proof-of-concept that RHDV evolution can be experimentally manipulated to select for virus variants with altered phenotypes, in this case partial immune escape.

  4. Epiphyseal distraction and centrally located bone bar: an experimental study in the rabbit.

    PubMed

    Cottalorda, J; Jouve, J L; Bollini, G; Panuel, M; Guisiano, B; Jimeno, M T

    1996-01-01

    The purpose of this study was to analyze the force required for an epiphysiolysis in vitro in the distal femoral growth plate of rabbits with different sized central physeal bone bars. The bars were operatively induced by drilling through the physis. An epiphyseal distraction was then performed, and the response was evaluated. Forty rabbits (67 femurs) divided into five groups were used for experimentation. Group A had not been operated on and manifested no physeal bone bridge. Groups B, C, D, and E manifested some bone bridges obtained surgically by drills 2, 2.5, 3.5, and 4.5 mm in diameter, respectively. The average force required to obtain an epiphysiolysis is not statistically significant in the different groups. However, we noted that the epiphysiolysis differed depending on the diameter of the surgically performed bridge. Group E was Salter-Harris type II fractures, whereas groups A, B, and C were type I fractures. Group D comprised both types.

  5. Current radiological techniques used to evaluate unilateral partial ureteral obstruction: an experimental rabbit study.

    PubMed

    Yazıcı, Mehmet; Celebi, Suleyman; Kuzdan, Özgür; Koçan, Hüseyin; Ayyıldız, Halil Suat; Bayrak, İlkay Koray; Bilgici, Meltem Ceyhan; Yapıcı, Oktay; Kefeli, Mehmet; Arıtürk, Ender

    2015-07-01

    The aim of this study was to evaluate functional and prognostic benefits of Doppler ultrasonography (DU), diuretic renal scintigraphy (DRS), and magnetic resonance urography (MRU) during diagnosis and follow-up of ureteropelvic junction obstruction (UPJO) and to examine apoptosis rates caused by UPJO in an experimental rabbit model. Twenty-four rabbits were divided randomly into two groups. The left kidneys of 15 rabbits from the first group underwent Ulm-Miller surgery to create UPJO, whereas the left kidneys of nine rabbits from the second group underwent sham surgery. A pressure flow study (Whitaker's test) was done during postoperative week 6. Based on the Whitaker test, the DU, DRS, and MRU findings were compared. The number of apoptotic renal cells was counted after death. The Whitaker test run during postoperative week 6 revealed obstructions in 15 rabbits from group 1; the nine rabbits of the sham group had no obstructions. Sensitivity and specificity of DRS were 93.3 and 88.8 %, respectively, and those of MRU were 93.3 and 88.8 %, respectively. The postoperative mean RI values were significantly higher than the preoperative values, associated with sensitivity of 86.6 % and specificity of 77.5 % for detecting UPJO. DRS, MRU, and RI could not predict UPJO in one (8 %), one (8 %), and two (16 %) kidneys, respectively. Likelihood ratio (LR) was 8.4 for MRU and scintigraphy, while for RI, LR was 3.9. Pathology specimens revealed that all kidneys with UPJO underwent apoptosis, and the number of apoptotic cells was significantly higher on the UPJO-created side than on the contralateral and in the sham group (p < 0.05). No test predicted all apoptosis related to UPJO. The RI, DRS, and DMRU results correlated with the pressure flow results for detecting UPJO. No single radiological technique predicted all initial UPJO-created kidneys that concluded with apoptosis. Further studies are required to seek with better methods for diagnosing an obstruction or to define a

  6. [Experimental study on the option of antispasmodic drugs for radial artery in elderly patients with coronary atherosclerotic heart disease].

    PubMed

    Shen, Liu-zhong; Chen, Xu-jun; Chen, Xin; Xu, Ming; Wang, Li-ming; Jiang, Ying-shuo

    2010-10-01

    To compare the relief effect of diltiazem, papaverine and nitroglycerin on radial artery spasm in elderly patients with coronary atherosclerotic heart disease. Sixty patients aged beyond 70 years underwent coronary artery bypass grafting (CABG) with autologous radial artery from July 2009 to March 2010. Redundant radial artery was collected and the relief function of different drugs was evaluated through "organ bath" technique in vitro. All the patients were randomly divided into 3 groups based on different antispasmodic drugs: diltiazem, papaverine and nitroglycerin. Thirty seconds free blood flow of radial artery and hemodynamic parameters (heart rate, mean arterial pressure and central venous pressure) were assessed before and after intra-radial administration of diltiazem, papaverine and nitroglycerin in vivo. All three drugs could relieve radial artery spasm in different levels and the eventual relief rate was over 80%. Only nitroglycerin could relax radial artery completely, the relief capacity of nitroglycerin, diltiazem and papaverine decreased in order. There was no significant difference in the hemodynamic parameters before and after the injection. Blood flow of radial artery increased in nitroglycerin group [(42 ± 10) ml/30 s vs. (28 ± 7) ml/30 s, P < 0.05] while there was no significant difference in diltiazem [(23 ± 10) ml/30 s vs. (25 ± 8) ml/30 s, P > 0.05] and papaverine group [(25 ± 10) ml/30 s vs. (24 ± 9), P > 0.05]. Nitroglycerin could relieve vasospasm of radial artery effectively and increased blood flow. Nitroglycerin is the suitable antispasmodic drug for radial artery in the elderly patients with coronary atherosclerotic heart disease compare with diltiazem and papaverine.

  7. Doppler sonography in experimentally induced acute renal failure in rabbits. Resistive index versus serum creatinine levels.

    PubMed

    Yoon, D Y; Kim, S H; Kim, H D; Na, D G; Goo, J M; Choi, H J; Yeon, K M; Han, M C

    1995-03-01

    The purpose of this study is to investigate the temporal relation between the change in the resistive index (RI) from renal Doppler sonography and that of serum creatinine values in the course of experimentally induced reversible acute renal failure (ARF) in rabbits. Reversible ARF was induced in 10 New Zealand white rabbits by injecting a glycerol solution (6.0 mL/kg) into the thigh muscle. Doppler sonography was performed before injection, and 6, 12, and 24 hours, and 3, 5, 7, and 14 days after injection of glycerol. Blood samples for measuring serum creatinine levels were obtained in the same time sequence. Three rabbits, which died during the course of the experiment, were excluded from the study group. The RI elevated rapidly after glycerol injection, peaked at 12 hours, and then decreased to normal values by 7 days. Conversely, serum creatinine values were elevated and peaked at 1 day and then decreased to normal by 14 days. The change in the RI preceded the change in serum creatinine levels in the course of reversible ARF. There was a weak linear correlation between RI and serum creatinine levels, with a correlation coefficient of 0.33. Doppler sonography with measurement of resistive index may be useful in predicting the course of ARF.

  8. Atypical myxomatosis--virus isolation, experimental infection of rabbits and restriction endonuclease analysis of the isolate.

    PubMed

    Psikal, I; Smíd, B; Rodák, L; Valícek, L; Bendová, J

    2003-08-01

    Atypical form of myxomatosis, which caused non-lethal and clinically mild disease in domestic rabbits 1 month after immunization with a commercially available vaccine MXT, is described. The isolated myxoma virus designated as Litovel 2 (Li-2) did not induce systemic disease following subcutaneous and intradermal applications in susceptible experimental rabbits but led to the immune response demonstrated by ELISA. No severe disease was induced in those Li-2 inoculated rabbits by challenge with the virulent strains Lausanne (Lu) or Sanar (SA), while the control animals showed nodular form of myxomatosis with lethal course of the illness. Restriction fragment length polymorphism (RFLP) of genomic DNA with KpnI and BamHI endonucleases was used for genetic characterization of the Li-2 isolate, the vaccine strain MXT and both virulent strains Lu and SA, respectively. In general, RFLP analysis has shown to be informative for inferring genetic relatedness between myxoma viruses. Based on restriction endonuclease DNA fragment size distribution, it was evident that the pathogenic strain SA is genetically related to the reference strain Lu and the isolate Li-2 is more related, but not identical, to the vaccination strain MXT.

  9. Effect of subcutaneously administered diclazuril on the output of Eimeria species oocysts by experimentally infected rabbits.

    PubMed

    Pan, B L; Zhang, Y F; Suo, X; Xue, Y

    2008-02-02

    The effect of subcutaneously injected diclazuril on the output of Eimeria species oocysts was studied in experimentally infected rabbits. Diclazuril was administered either prophylactically at 0.5, 1 or 2 mg/kg bodyweight two days before each rabbit was inoculated with 20,000 oocysts of a mixed-species field isolate of Eimeria or therapeutically at 1, 2 or 4 mg/kg bodyweight five days after they were inoculated. The prophylactic treatments significantly reduced (P<0.05) the output of oocysts in faeces and the numbers in the rabbits' livers at all doses. The therapeutic treatment at 4 mg/kg also caused a significant reduction (P<0.05) in oocyst shedding, but the lower doses resulted in only a moderate reduction. The shedding of the pathogenic species Eimeria stiedae, Eimeria magna, Eimeria irresidua, Eimeria flavescens, Eimeria piriformis and Eimeria intestinalis was significantly reduced (P<0.05) in all the treated groups. The burden of oocysts in the livers of the therapeutic groups (4000 to 9000) were significantly lower (P<0.05) than in the inoculated but untreated control group (23,000), but higher than in the prophylactic groups (around 1000).

  10. EFFECT OF USE OF BONE-MARROW CENTRIFUGATE ON MUSCLE INJURY TREATMENT: EXPERIMENTAL STUDY ON RABBITS

    PubMed Central

    Vieira, Daniel Ferreira Fernandes; Guarniero, Roberto; Vaz, Carlos Eduardo Sanches; de Santana, Paulo José

    2015-01-01

    Objective: The objective of this study was to evaluate the effect of bone-marrow centrifugate on the healing of muscle injuries in rabbits. Methods: This experimental study involved use of fifteen adult male New Zealand White rabbits. Each animal received a transverse lesion in the middle of the right tibialis anterior muscle, to which an absorbable collagen sponge, soaked in a centrifugate of bone marrow aspirate from the ipsilateral iliac bone, was added. The left hind limb was used as a control and underwent the same injury, but in this case only the absorbable collagen sponge. Thirty days later, the animals were sacrificed to study the muscle healing. These muscle areas were subjected to histological analysis with histomorphometry, with the aim of measuring the number of muscle cells per square micrometer undergoing regeneration and the proportion of resultant fibrosis. Results: The centrifugation method used in this study resulted in an average concentration of nucleated cells greater than the number of these cells in original aspirates, without causing significant cell destruction. Addition of the bone marrow centrifugate did not result in any significant increase in the number of muscle cells undergoing regeneration, in relation to the control group. There was also no significant difference in the proportion of resultant fibrosis, compared with the control group. Conclusion: Administration of the bone marrow centrifugate used in this study did not favor healing of muscle injuries in rabbits. PMID:27047832

  11. Ginkgo biloba extract inhibits the development of experimental atherosclerosis in rabbits.

    PubMed

    Wójcicki, J; Samochowiec, L; Juźwiak, S; Gonet, B; Syryński, W; Barcew-Wiszniewska, B; Roźewicka, L; Tustanowski, S; Ceglecka, M; Juzyszyn, Z; Myśliwlec, Z; Kałdonska, M; Górnik, W; Kadłubowska, D

    1994-06-01

    Forty male mongrel rabbits were divided into 4 equal groups: (1) controls, (2) animals receiving a high-fat diet (HFD) containing cholesterol and coconut oil, (3) HFD + standardized. Ginkgo biloba extract (GB), and (4) HFD + rutin (as a well known substance it was used for comparison of pure single flavonol diglycoside activity with total extract). The experiment lasted 12 weeks. The most pronounced reduction in lipid metabolism disturbances and in the severity of plaque formation occurred after the GB had been administered. Lipid content in serum, liver homogenate and liver microsomes was depressed. HDL-cholesterol concentration was increased. Diminution of the malondialdehyde level in plasma was accompanied by an increase in the concentration of ascorbate free radicals in the liver in vitro. Testosterone concentrations in serum were normalized whilst the cytochrome P-450 content in liver microsomes was increased. Surface area of the lipid deposits at 12 weeks measured planimetrically averaged 85.5 % in HFD-fed animals vs 54.7 % in GB-treated rabbits. Quite distinct superiority of GB in antiatherosclerotic activity, as compared with rutin, was shown. These findings suggest that GB, in addition to lowering serum lipid level and possessing antioxidant properties in rabbits on an experimental diet, also affects metabolic processes in the liver and may modify lipid deposition in major arteries. Copyright © 1994 Gustav Fischer Verlag, Stuttgart · Jena · New York. Published by Elsevier GmbH.. All rights reserved.

  12. Histopathological findings in rabbits after experimental acute exposure to the Loxosceles intermedia (brown spider) venom

    PubMed Central

    Ospedal, Katia Zoghbi; Appel, Marcia Helena; Neto, José Fillus; Mangili, Oldemir Carlos; Veiga, Silvio Sanches; Gremski, Waldemiro

    2002-01-01

    Loxoscelism, the term used to describe envenomation with brown spiders, is characterized by a dermonecrotic lesion at the bite site. In the present investigation we submitted albino rabbits to an acute experimental envenomation protocol using Loxosceles intermedia (brown spider) venom, with in order to determine the pathogenesic features of the lesion induced by this spider, which is the cause of several accidents throughout the world. Rabbits received intradermal injections of the venom and were monitored over the first 4 h, and then at 12 h and 1, 2 and 5 days after envenomation. Histological specimens from 3 rabbits per time point were collected from euthanized animals and processed for histological examination by light microscopy. Major findings observed during the first 4 h were oedema, haemorrhage, degeneration of blood vessel walls, plasma exudation, thrombosis, neutrophil accumulation in and around blood vessels with an intensive diapedesis, a diffuse collection of inflammatory cells (polymorphonuclear leucocytes) in the dermis, and subcutaneous muscular oedema. Over the following hours and up to 5 days after envenomation the changes progressed to massive neutrophil infiltration (with no other leucocytes) into the dermis and even into subcutaneous muscle tissue, destruction of blood vessels, thrombosis, haemorrhage, myonecrosis, and coagulative necrosis on the 5th day. PMID:12657137

  13. Histopathological findings in rabbits after experimental acute exposure to the Loxosceles intermedia (brown spider) venom.

    PubMed

    Ospedal, Katia Zoghbi; Appel, Marcia Helena; Fillus Neto, José; Mangili, Oldemir Carlos; Sanches Veiga, Silvio; Gremski, Waldemiro

    2002-12-01

    Loxoscelism, the term used to describe envenomation with brown spiders, is characterized by a dermonecrotic lesion at the bite site. In the present investigation we submitted albino rabbits to an acute experimental envenomation protocol using Loxosceles intermedia (brown spider) venom, with in order to determine the pathogenesic features of the lesion induced by this spider, which is the cause of several accidents throughout the world. Rabbits received intradermal injections of the venom and were monitored over the first 4 h, and then at 12 h and 1, 2 and 5 days after envenomation. Histological specimens from 3 rabbits per time point were collected from euthanized animals and processed for histological examination by light microscopy. Major findings observed during the first 4 h were oedema, haemorrhage, degeneration of blood vessel walls, plasma exudation, thrombosis, neutrophil accumulation in and around blood vessels with an intensive diapedesis, a diffuse collection of inflammatory cells (polymorphonuclear leucocytes) in the dermis, and subcutaneous muscular oedema. Over the following hours and up to 5 days after envenomation the changes progressed to massive neutrophil infiltration (with no other leucocytes) into the dermis and even into subcutaneous muscle tissue, destruction of blood vessels, thrombosis, haemorrhage, myonecrosis, and coagulative necrosis on the 5th day.

  14. Immunoelectrophoretic Studies of Sera from Rabbits Experimentally Infected with Histoplasma capsulatum

    PubMed Central

    Adamson, David M.; Cozad, George C.

    1966-01-01

    Adamson, David M. (University of Oklahoma, Norman), and George C. Cozad. Immunoelectrophoretic studies of sera from rabbits experimentally infected with Histoplasma capsulatum. J. Bacteriol. 92:887–891. 1966.—In a study involving 24 mature Dutch rabbits inoculated intravenously with 2.6 × 108Histoplasma capsulatum yeast cells per kg of body weight, all rabbits were shown to develop precipitins by the end of the 5th week. Precipitins were demonstrated both by the micro-Ouchterlony method and microimmunoelectrophoresis with the use of concentrated histoplasmin as the antigen. The latter technique proved to be the more sensitive. The 10 × concentrate of histoplasmin gave better precipitin patterns than did the 5 × concentrate. Agglutinins were formed by 90% of the rabbits by the end of the 4th week, as shown by the capillary tube agglutination test. Three precipitin bands, arbitrarily designated A, B, and C, were demonstrated by immunoelectrophoresis with use of the sera of the test animals. Band A occurred between the 1st and 2nd weeks after inoculation and was, for a period, present in 100% of the sera of the test animals. Band A occurred separately or in conjunction with band B or B and C, and it persisted longer than these other two bands. Bands B and C appeared between the 3rd and 4th weeks and were found, by the end of the 5th week, in 35 and 15%, respectively, of the sera tested. They were never seen separately or together without the presence of band A. Band C disappeared by the end of the 6th week, and band B, by the 10th week, but band A was still present in 19% of the sera at the end of 10 weeks. PMID:5926755

  15. STUDIES ON THE ETIOLOGY OF RABBIT POX : II. CLINICAL CHARACTERISTICS OF THE EXPERIMENTALLY INDUCED DISEASE.

    PubMed

    Rosahn, P D; Hu, C K; Pearce, L

    1936-01-31

    The clinical manifestations and course of disease observed in experimental rabbit pox have been described and analyzed. The condition differed from the acute fulminating and rapidly fatal type of experimental infection (1) in that the period of survival was longer, a variety of clinical manifestations developed and a considerable proportion of the cases recovered. The most conspicuous symptom was a generalized papular eruption on the skin and mucocutaneous borders. The production of the disease was associated with routes of inoculation other than the intratesticular or with a small dosage. The majority of cases were inoculated with Berkefeld V filtrates of tissue-virus emulsions and not with the more potent unfiltered emulsions. The local reactions resulting from various routes of inoculation were described. Of special interest were the pronounced cutaneous reactions induced by intradermal injection, the high instance of marked clinical manifestations after intravenous inoculation, the failure of lesions to localize in the lines of scarification of skin and cornea even in cases with a profuse cutaneous eruption, and the development of cytoplasmic inclusion bodies in the epithelial cells of the cornea following scarification and conjunctival instillation of virus. In the character of its clinical manifestations and course of disease, experimental rabbit pox was indistinguishable from cases of the spontaneous pox.

  16. Experimental allergic neuritis-like disease in rabbits after injection with influenza vaccines mixed with gangliosides and adjuvants.

    PubMed Central

    Ziegler, D W; Gardner, J J; Warfield, D T; Walls, H H

    1983-01-01

    An experimental allergic neuritis-like disease was induced in rabbits 3 to 8 weeks after injection with large doses of influenza vaccines mixed with gangliosides, cholesterol, and Freund complete adjuvant. The inclusion of gangliosides was essential to induce the experimental allergic neuritis-like disease. In trials with six different lots of vaccine, both swine influenza and non-swine influenza vaccines produced by four different manufacturers induced experimental allergic neuritis-like disease in 26 of 43 inoculated rabbits. Images PMID:6642653

  17. Radiographic assessment of the femorotibial joint of the CCLT rabbit experimental model of osteoarthritis

    PubMed Central

    2010-01-01

    osteophytes (rs = 0.64, p < 0.001). Conclusion Non-invasive in vivo radiography of the rabbit femorotibial joint is feasible, relevant and allows a reproducible grading of experimentally induced OA lesion. The radiographic grading scale and atlas presented could be used as a template for in vivo non invasive grading of ROA in preclinical studies and could allow future comparisons between studies. PMID:20089151

  18. An experimental model for studies on delayed tooth replantation and ankylosis in rabbits.

    PubMed

    Maslamani, Manal; Almusawi, Ala; Joseph, Bobby; Gabato, Severino; Andersson, Lars

    2016-12-01

    To develop an experimental in vivo model to study dentoalveolar ankylosis and osseous replacement resorption after delayed replantation. The maxillary right incisors of eight rabbits were extracted and replanted, while the maxillary left incisors served as controls. A special technique for extraction was used, luxating the incisor laterally prior to extraction. Extra-oral root canal treatment was performed. In four of the eight replanted teeth, periodontal ligament was removed using gauze. All teeth were replanted after one-hour dry storage. A horizontal line was drilled on the labial enamel surface of the incisors to enable registration of possible subsequent infraposition. The rabbits were sacrificed after 1 week or 4 weeks, respectively. Percussion test of the teeth was carried out and infraposition was registered. Histological processing and evaluation were performed. Percussion sound was normal after 1 week and high in the 4 week group; infraposition was noted in all replanted teeth in the 4-week group. Fusion between the bone and dentin was seen in some areas on the root already after 1 week, but there was little or no osseous replacement. Larger areas of ankylosis were seen in the 4-week group although not significant, but deeper progressive osseous replacement was noted in this group. There was no significant difference in ankylosis with regard to periodontal ligament removal or not. Pulp and periodontal tissues were normal in all control teeth. The rabbit tooth model may be useful for experimental in-vivo studies on delayed replantation, subsequent ankylosis, osseous replacement and infraposition. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Quantitative SEM analysis of injury to the endothelium of rabbit aorta and carotid artery during experimental atherosclerosis.

    PubMed

    Zaikina, O E; Dolgov, V V; Ivanov, V N; Bondarenko, M F; Repin, V S

    1982-02-01

    The luminal surface of the aorta and the carotid artery in normal and cholesterol-fed rabbits (3 weeks, 6 weeks, and 8 months of alimentary hypercholesterolemia) was studied by scanning electron microscopy (SEM). To study endothelial injury the vessels were perfused and stained under physiological pressure. The frequency of large and small endothelial defects was determined per surface unit of endothelium in the normal and experimental groups of rabbits. Loss of endothelial cells was regarded as a large defect, argyrophilic cells, craters, and stomata were regarded as small ones. It was found that the percentage of regions without endothelial cells was similar in both control rabbits and in rabbits with experimental atherosclerosis (0.005--0.04% of the total surface examined). The frequency of small endothelial defects increased in rabbits after 3 weeks of hypercholesterolemia but decreased to the control level after 6 weeks of hypercholesterolemia. In rabbits with 8 months of hypercholesterolemia the frequency and area of defects outside plaques did not differ from the control group. In the group with hypercholesterolemia for 8 months 39.2% of the plaque surface contained endothelial cells in which there were no distinct silver-stained cell borders. Kevex X-ray spectrometric data of silver topography indicated that the plaque surface without distinct cell borders was not an area devoid of cells. The data obtained do not support the assumption that morphological endothelial injury is the structural precursor of plaque formation.

  20. Molecular diagnosis of Eimeria stiedae in hepatic tissue of experimentally infected rabbits.

    PubMed

    Hassan, Khaled M; Arafa, Waleed M; Mousa, Waheed M; Shokier, Khaled A M; Shany, Salama A; Aboelhadid, Shawky M

    2016-10-01

    The early detection of Eimeria stiedae in the hepatic tissue of experimentally infected rabbits was investigated using molecular assay. Forty 6-week-old male New Zealand rabbits were divided into two groups. Group A (30 animals) was infected with 2.5 × 10(4) sporulated oocysts of E. stiedae per animal on Day 0 and Group B (10 animals) was used as the uninfected controls. Three animals from Group A and one from Group B were sacrificed at 0, 3, 6, 9, 12, 15, 18, 21, 24 and 27 days post infection (PI). Gross and microscopic post-mortem findings were recorded. Polymerase chain reaction (PCR) of the E. stiedae internal transcribed spacer 1 genomic region was conducted on blood, liver tissue, and feces from the Group A experimentally infected animals. Macroscopically, the liver showed irregular yellowish white nodules pathognomonic to E. stiedae infection beginning on Day 15 PI. Hepatomegaly and ascites were obvious from Day 21-24 PI. The presence of different E. stiedae schizonts and gametocytes in the histopathological sections of the biliary epithelium were evident on Day 15 PI. The E. stiedae PCR was first positive in liver tissues on Day 12 and in fecal samples on Day 18 PI, but the blood samples were negative. In conclusion, the PCR can be used for early diagnosis and control of E. stiedae schizonts before shedding of the oocysts in feces.

  1. Fursultiamine, a vitamin B1 derivative, enhances chondroprotective effects of glucosamine hydrochloride and chondroitin sulfate in rabbit experimental osteoarthritis.

    PubMed

    Kobayashi, T; Notoya, K; Nakamura, A; Akimoto, K

    2005-06-01

    The therapeutic effect of glucosamine hydrochloride (GH) and chondroitin sulfate (CS) in combination with fursultiamine, a vitamin B1 derivative, on the development of cartilage lesions was investigated in an animal model of osteoarthritis (OA). The OA model was created by partial medial meniscectomy of the right knee joint (day 0). The rabbits were placed into three experimental groups: operated (OA) rabbits that received placebo treatment, OA rabbits that received GH (1000 mg/kg) + CS (800 mg/kg), and OA rabbits that received GH + CS + fursultiamine (100 mg/kg). Each treatment was initiated on day 3 and continued for 8 weeks. Macroscopic and histologic analyses were performed on the cartilage. The level of MMP-1 in OA cartilage chondrocytes was evaluated by immunohistochemistry. Only the group receiving combined treatment with GH + CS + fursultiamine showed a significant reduction in the severity of macroscopic and histologic lesions on tibial plateau, which is the weight bearing cartilage surface of the tibia, compared with placebo-treated OA rabbits. This treatment group also revealed a small, but significant, decrease in the body weight gain of the rabbits. In cartilage from placebo-treated OA rabbits, a significantly higher percentage of chondrocytes in superficial layer stained positive for MMP-1 compared with unoperated control. Rabbits treated with the GH + CS + fursultiamine revealed a significant reduction in the level of MMP-1. These results suggest that the chondroprotective effect of GH + CS is enhanced by the addition of fursultiamine in experimental OA. This effect was associated with a reduction in the level of MMP-1, which are known to play an important role in the pathophysiology of OA lesions.

  2. An evaluation of biocompatibility of indigenously produced pure titanium: an experimental study in rabbits.

    PubMed

    Chittaranjan, Bhogisetty; Murthy, Late Bhamidipati Sreerama; Ravindranath, Turaga

    2012-10-01

    The indigenously produced pure titanium dental implants are economical and useful for common human use in India. The aim of this study is to test the biocompatibility of the indigenously produced pure titanium dental implant material obtained from the Defense Metallurgical Research Laboratory, Hyderabad, India, and the Institute of Nuclear Medicine and Allied Science, Delhi, India. An experimental study in rabbits was done to study the amount of ordered bone formation around the screw and cylinder type of indigenously produced pure titanium metal implant specimens. The experimental animals were killed at 4, 6, 8, 12, and 16 weeks from the date of implantation. The histopathological examination of the animals killed at 16 weeks demonstrates the presence of osteoblastic cell proliferation and early ordered bone formation toward the implant site, indicating signs of osseointegration of both screw- and cylinder-type indigenously produced pure titanium specimens.

  3. Healing pattern of experimental soft tissue lacerations after application of novel topical anesthetic agents - an experimental study in rabbits.

    PubMed

    Al-Asfour, Adel; Al-Melh, Manal; Andersson, Lars; Joseph, Bobby

    2008-02-01

    Topical anesthetics based on a combination of 2.5% lidocaine and 2.5% prilocaine are efficient in eliminating pain from needle stick when placed on skin and oral mucosa. This suggests their application in soft tissue lacerations before suturing to enable pain-free exploration and suturing of traumatic lacerations without prior injection needle stick. The aim of the present study was to study the healing of experimental oral lacerations after topical anesthetic substances were placed in the lacerations. Thirty-six standardized incisions were made bilaterally in the lower and the upper labial mucosa of nine white New Zealand rabbits. All wounds were intentionally contaminated with saliva to simulate laceration wounds in trauma situation. EMLA cream and Oraqix thermosetting gel were applied into 30 lacerations and six lacerations were left untreated as control. In some lacerations the topical anesthetic agent was left in the wound, while in others they were rinsed off by saline before suturing the laceration wound. The rabbits were then killed after 3 days, 2 weeks and 4 weeks of healing and the lips were processed for histological evaluation. Similar normal histological healing patterns were seen in wounds in which EMLA and Oraqix were applied compared with control lacerations at all stages of healing. No adverse tissue or foreign body reactions were seen in any of the lacerations. We conclude that EMLA and Oraqix can be used in oral mucosal lacerations prior to suturing without the risk of adverse tissue reaction.

  4. Experimental retinal detachment causes widespread and multilayered degeneration in rabbit retina.

    PubMed

    Faude, F; Francke, M; Makarov, F; Schuck, J; Gärtner, U; Reichelt, W; Wiedemann, P; Wolburg, H; Reichenbach, A

    2001-05-01

    Retinal detachment remains one of the most frequent causes of visual impairment in humans, even after ophthalmoscopically successful retinal reattachment. This study was aimed at monitoring (ultra-) structural alterations of retinae of rabbits after experimental detachment. A surgical procedure was used to produce local retinal detachments in rabbit eyes similar to the typical lesions in human patients. At various periods after detachment, the detached retinal area as well as neighbouring attached regions were studied by light and electron microscopy. In addition to the well-known degeneration of photoreceptor cells in the detached retina, the following progressive alterations were observed, (i) in both the detached and the attached regions, an incomplete but severe loss of ganglion cell axons occurs; (ii) there is considerable ganglion cell death, particularly in the detached area; (iii) even in the attached retina distant from the detachment, small adherent groups of photoreceptor cells degenerate; (iv) these photoreceptor cells degenerate in an atypical sequence, with severely destructed somata and inner segments but well-maintained outer segments; and (v) the severe loss of retinal neurons is not accompanied by any significant loss of Müller (glial) cells. It is noteworthy that the described progressive (and probably irreparable) retinal destructions occur also in the attached retina, and may account for visual impairment in strikingly large areas of the visual field, even after retinal reattachment.

  5. Experimentally infected human body lice (pediculus humanus humanus) as vectors of Rickettsia rickettsii and Rickettsia conorii in a rabbit model.

    PubMed

    Houhamdi, Linda; Raoult, Didier

    2006-04-01

    The human body louse, the natural vector of Rickettsia prowazekii, is able to experimentally transmit the normally flea-borne rickettsia R. typhi, suggesting that the relationships between the body louse and rickettsiae are not specific. We used our experimental infection model to test the ability of body lice to transmit two prevalent tick-borne rickettsiae. Each of two rabbits was made bacteremic by injecting intravenously 2 x 10(6) plaque-forming units of either R. rickettsii or R. conorii. Four hundred body lice were infected by feeding on the bacteremic rabbit and were compared with 400 uninfected lice. Each louse group was fed once a day on a separate seronegative rabbit. The survival of infected lice was not different from that of uninfected controls. Lice remained infected for their lifespan, excreted R. rickettsii and R. conorii in their feces, but did not transmit the infection to their progeny. The nurse rabbit of uninfected lice remained asymptomatic and seronegative. Those rabbits used to feed infected lice developed bacteremia and seroconverted. Although the body louse is not a known vector of spotted fevers, it was able in our study to acquire, maintain, and transmit both R. rickettsii and R. conorii.

  6. Intravascular electric impedance spectroscopy of atherosclerotic lesions using a new impedance catheter system.

    PubMed

    Süselbeck, T; Thielecke, H; Köchlin, J; Cho, S; Weinschenk, I; Metz, J; Borggrefe, M; Haase, K K

    2005-09-01

    Newer techniques are required to identify atherosclerotic lesions that are prone to rupture. Electric impedance spectroscopy (EIS) can characterize biological tissues by measuring the electrical impedance over a frequency range. We tested a newly designed intravascular impedance catheter (IC) by measuring the impedance of different stages of atherosclerosis induced in an animal rabbit model. Six female New Zealand White rabbits were fed for 17 weeks with a 5% cholesterol-enriched diet to induce early forms of atherosclerotic plaques. All aortas were prepared from the aortic arch to the renal arteries and segments of 5-10 mm were marked by ink spots. A balloon catheter system with an integrated polyimide-based microelectrode structure was introduced into the aorta and the impedance was measured at each spot by using an impedance analyzer. The impedance was measured at frequencies of 1 kHz and 10 kHz and compared with the corresponding histomorphometric data of each aortic segment.Forty-four aortic segments without plaques and 48 segments with evolving atherosclerotic lesions could be exactly matched by the histomorphometric analysis. In normal aortic segments (P0) the change of the magnitude of impedance at 1 kHz and at 10 kHz (|Z|(1 kHz) - |Z|(10 kHz), = ICF) was 208.5 +/- 357.6 Omega. In the area of aortic segments with a plaque smaller than that of the aortic wall diameter (PI), the ICF was 137.7 +/- 192.8 Omega. (P 0 vs. P I; p = 0.52), whereas in aortic segments with plaque formations larger than the aortic wall (PII) the ICF was significantly lower -22.2 +/- 259.9 Omega. (P0 vs. PII; p = 0.002). Intravascular EIS could be successfully performed by using a newly designed microelectrode integrated onto a conventional coronary balloon catheter. In this experimental animal model atherosclerotic aortic lesions showed significantly higher ICF in comparison to the normal aortic tissue.

  7. Studies on the Pathogenesis of Experimental Chronic Active Hepatitis in Rabbits

    PubMed Central

    Hopf, U.; Meyer zum Büschenfelde, K.-H.

    1974-01-01

    Isolated hepatocytes of rabbits with experimentally induced chronic active hepatitis (CAH) in different stages and liver cirrhosis, respectively, and of animals without liver lesions were studied by immunofluorescence with regard to surface bound immunoglobulin. In 8 of 9 animals with CAH immunoglobulin could be demonstrated on the membranes of the hepatocytes. One animal with liver cirrhosis did not show fixed gammaglobulin; 8 animals without liver lesions which had been immunized with xenogeneic (human) together with allogeneic liver specific proteins (RLP) had no immunoglobulin bound to their hepatocytes, with one exception. The antibody titres in the serum of these animals against liver specific proteins (passive haemagglutination and gel diffusion) were not different from those in animals with liver lesions. The skin test reactivity with RLP as antigen corresponded largely to the development of liver lesions. The pathogenic importance of an antibody mediated lymphocytic cytotoxicity for the induction of CAH is discussed. ImagesFig. PMID:4217635

  8. Pharmacokinetics of phenazone (antipyrine) in rabbits with experimental common bile duct obstruction.

    PubMed

    Wójcicki, J; Sulikowski, T; Wójcicki, M; Droździk, M; Gawrońska-Szklarz, B; Barcew-Wiszniewska, B; Skowron, J; Rózewicka, L

    1996-01-01

    1. An altered functional state of liver due to experimental cholestasis could result in a change in the biotransformation of drugs. The aim of this study was to evaluate an influence of obstructive cholestasis on the pharmacokinetics of phenazone (antipyrine). 2. The investigation was carried out on male rabbits, randomly allocated into two groups: shamoperated and animals with biliary ducts ligation. Phenazone was administered intragastrically as a probe of drug metabolism. 3. Measurements, i.e. laboratory and pharmacodynamic tests, as well as pharmacokinetic assays, were performed before the operation as well as 10-12 days after the bile duct ligation. At the end of the study livers were examined macro- and microscopically and biochemical analysis of the liver microsomes was performed. 4. The measured pharmacokinetic parameters suggested an impaired biotransformation of phenazone in animals with obstructive cholestasis, leading to a slower drug elimination.

  9. Stem cells from the fat tissue of rabbits: an easy-to-find experimental source.

    PubMed

    Torres, Fabrício Carvalho; Rodrigues, Consuelo Junqueira; Stocchero, Ithamar Nogueira; Ferreira, Marcus Castro

    2007-01-01

    Stem cells, because of their pluripotentiality and unlimited capacity for self-renewal, project great promise for tissue engineering and are expected to allow significant advances for distinct reconstructive procedures. This study aimed to establish a versatile experimental model with potential application to distinct lines of research in plastic surgery. The search was guided by the need for mesenchymal stem cells that can be easily obtained for laboratory research. The authors studied the anatomy of a number of animals as potential donors and indicated the white New Zealand rabbit (Oryctolagus cuniculus) for this purpose. The animals of this species present definite areas of lipid tissue on their back, allowing easy access to the tissue by either exeresis or liposuction.

  10. Experimental chronic active hepatits in rabbits following immunization with human liver proteins

    PubMed Central

    Büschenfelde, K. H. Meyer Zum; Kössling, F. K.; Miescher, P. A.

    1972-01-01

    Two liver-specific antigens are known: a water soluble protein (LP-2) and a water insoluble macromolecular low density lipoprotein (LP-1). In this paper the relative role of the two antigens in the development of experimental immune hepatitis has been investigated. Immunization of rabbits with a human preparation containing both antigens, led in all animals to lesions characteristic of an immune hepatitis. Immunization of the animals with a purified water soluble liver protein proved less efficient: only two out of six animals developed characteristic lesions which were less severe than those in the first group. It was deduced that although not a prerequisite, the liver-specific lipoprotein plays an important supportive role in the development of immune hepatitis. ImagesFig. 2Fig. 1Fig. 3 PMID:4338952

  11. Bioactive glass in cavitary bone defects: a comparative experimental study in rabbits

    PubMed Central

    Camargo, André Ferrari de França; Baptista, André Mathias; Natalino, Renato; de Camargo, Olavo Pires

    2015-01-01

    OBJECTIVES: To compare bioactive glass and autograft regarding their histomorphometric characteristics. METHODS: The authors conducted a prospective case-control experimental study on animals in order to compare the histomorphometric characteristics of bioactive glass versus autograft. Eight rabbits underwent surgery in which a cavitary defect was created in both proximal femurs. One side was filled with bioactive glass granules and the other, with autograft grafted from the contralateral side. The sides were randomized. Fourteen days after surgery, the animals were euthanized. RESULTS: Histologic analysis revealed that bone neoformation was equivalent among the two groups and the osteoblasts cell-count was higher in the femurs treated with bioactive glass. The osteocytes cell-count, however, was lower. The similarity in bone formation between both groups was consistent to literature findings. CONCLUSION: Bioactive glass is similar to autograft regarding bone neoformation in this animal model of cavitary bone defects. Level of Evidence III, Case-Control Study. PMID:26327802

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

    PubMed Central

    Arias-Mutis, Oscar Julián; Marrachelli, Vannina G.; Ruiz-Saurí, Amparo; Alberola, Antonio; Morales, Jose Manuel; Such-Miquel, Luis; Monleon, Daniel; Chorro, Francisco J.; Such, Luis

    2017-01-01

    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 problems related to Met

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

    PubMed

    Arias-Mutis, Oscar Julián; Marrachelli, Vannina G; Ruiz-Saurí, Amparo; Alberola, Antonio; Morales, Jose Manuel; Such-Miquel, Luis; Monleon, Daniel; Chorro, Francisco J; Such, Luis; Zarzoso, Manuel

    2017-01-01

    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 problems related to Met

  14. White and red blood cell picture in rabbits experimentally infected with strains of the rabbit haemorrhagic disease (RHD) virus without or with variable haemagglutination capacity.

    PubMed

    Niedźwiedzka-Rystwej, P; Tokarz-Deptuła, B; Deptuła, W

    2016-12-01

    The aim of the study was to establish if haemagglutination of rabbit haemorrhagic disease virus (RHDV) affects haematological picture of peripheral blood in rabbits and the pathogenicity of the virus. The study analyzed white and red blood cell picture in rabbits experimentally infected with two non-haemagglutinating (HA-) RHDV strains (Frankfurt and Asturias) and one strain with variable haemagglutination capacity (HA+/-) (Hagenow). Studies with HA- and HA +/- are rare and relate only to 4 HA- strains (2 RHDV: BLA and Rainham; 2 RHDVa: Pv97 and 9905) and 1 HA+/- RHDV strain: ŻD, where less changes in haematological indices and less pathogenicity were observed. We found that changes caused by HA- Frankfurt strain were related to the number of neutrophils and thrombocytes, while in HA- strain Asturias, in thrombocytes and leukocytes. Changes evoked by HA+/- Hagenow strain pertained to the number of eosinophils, thrombocytes, leukocytes, monocytes, and concentration of hemoglobin. Mortality caused by the Frankfurt strain was 100% between 36 and 48 h post infection (p.i.), while that caused by Asturias strain was 100% between 24 and 36 h p.i., and that observed in case of Hagenow strain was 90% between 36 and 48 h p.i. The changes in haematological picture caused by the HA- and HA+/- RHDV strains were less intensive than those found in case of the HA+ RHDV strains, which cannot be confirmed for pathogenicity, and is not in line with the existing hypothesis suggesting higher pathogenicity in HA+ viruses.

  15. Experimental study of pathogenicity of Pasteurella multocida serogroup F in rabbits.

    PubMed

    Jaglic, Zoran; Jeklova, Edita; Leva, Lenka; Kummer, Vladimir; Kucerova, Zdenka; Faldyna, Martin; Maskova, Jarmila; Nedbalcova, Katerina; Alexa, Pavel

    2008-01-01

    The role of Pasteurella multocida serogroup F in inducing disease in rabbits was investigated in this study. Three groups of 12 Pasteurella-free rabbits each were intranasally (i.n.), subcutaneously (s.c.), and perorally (p.o.) challenged, respectively. Six rabbits of each group were immunosuppressed using dexamethasone. Eight rabbits (four of them immunosuppressed) inoculated i.n. showed symptoms of respiratory distress resulting in respiratory failure and died or were euthanized in the terminal stage of the disease 3-6 days post-infection (p.i.). The main pathological findings were fibrinopurulent pleuropneumonia (immunocompetent rabbits) or diffuse haemorrhagic pneumonia (immunosuppressed rabbits). Septicemic syndrome ending with shock occurred in 11 rabbits (6 of them immunosuppressed) inoculated s.c., which died or were euthanized in the terminal stage of the disease 2-3 days p.i. The most significant pathological findings were extensive cutaneous and subcutaneous lesions. All of the p.o. inoculated rabbits survived the challenge showing no clinical signs of the disease and no macroscopic lesions. The observations in this study indicate that in addition to serogroups A and D of P. multocida, serogroup F also can be highly pathogenic for rabbits and therefore might be a cause of considerable economic loss in commercial rabbit production.

  16. Cerebrospinal fluid outflow resistance in rabbits with experimental meningitis. Alterations with penicillin and methylprednisolone.

    PubMed Central

    Scheld, W M; Dacey, R G; Winn, H R; Welsh, J E; Jane, J A; Sande, M A

    1980-01-01

    Acute bacterial meningitis may be associated with increased intracranial pressure, neurological sequelae such as communicating hydrocephalus, and a slow response to antibiotic therapy. Alterations in cerebrospinal hydrodynamics are at least partially responsible for these complications. Constant, low-flow short-duration manometric infusion studies through a hollow-bore pressure monitoring device in direct continuity with the supracortical subarachnoid space were performed in rabbits with experimental meningitis. Maximal resistance to cerebrospinal fluid (CSF) outflow from the subarachnoid to vascular space was markedly increaed in acute pneumococcal meningitis when compared to control, uninfected animals (6.77 +/- 3.52 vs. 0.26 +/- 0.04 mm Hg/microliter per min, P less than 0.001). Similar elevations (8.93 +/- 4.15 mm Hg/microliter per min were found in experimental Escherichia coli meningitis. Despite eradication of viable bacteria from the CSF by penicillin therapy during the acute stage of pneumococcal meningitis, resistance remained elevated (6.07 +/- 4.68 mm Hg/microliter per min) and had not returned to normal up to 15 d later. Administration of methylprednisolone during the early stages of acute pneumococcal meningitis reduced mean peak outflow resistance towards control values (0.59 mm Hg/microliter per min) and no "rebound" effect was apparent 24 h later. These hydrodynamic alterations in experimental meningitis prevent normal CSF absorption and decrease the ability of the bran to compensate for changes in intracranial volume and pressure. PMID:6995482

  17. Atherosclerotic changes of vessels caused by restriction of movement

    NASA Technical Reports Server (NTRS)

    Gvishiani, G. S.; Kobakhidze, N. G.; Mchedlishvili, M. G.; Dekanosidze, T. I.

    1980-01-01

    The effect of restriction of movement on the development of atheroscelerosis was studied in rabbits. Drastic restriction of movement for 20 and 30 days causes atherosclerotic alterations of the aorta and shifts in ECG which are characteristic of coronary atherosclerosis. At the same time, shortening of the duration of blood coagulation and an increase in the content of catecholamines and beta-lipoproteids occur.

  18. Experimental West Nile Virus Infection in Rabbits: An Alternative Model for Studying Induction of Disease and Virus Control

    PubMed Central

    Suen, Willy W.; Uddin, Muhammad J.; Wang, Wenqi; Brown, Vienna; Adney, Danielle R.; Broad, Nicole; Prow, Natalie A.; Bowen, Richard A.; Hall, Roy A.; Bielefeldt-Ohmann, Helle

    2015-01-01

    The economic impact of non-lethal human and equine West Nile virus (WNV) disease is substantial, since it is the most common presentation of the infection. Experimental infection with virulent WNV strains in the mouse and hamster models frequently results in severe neural infection and moderate to high mortality, both of which are not representative features of most human and equine infections. We have established a rabbit model for investigating pathogenesis and immune response of non-lethal WNV infection. Two species of rabbits, New Zealand White (Oryctolagus cuniculus) and North American cottontail (Sylvilagus sp.), were experimentally infected with virulent WNV and Murray Valley encephalitis virus strains. Infected rabbits exhibited a consistently resistant phenotype, with evidence of low viremia, minimal-absent neural infection, mild-moderate neuropathology, and the lack of mortality, even though productive virus replication occurred in the draining lymph node. The kinetics of anti-WNV neutralizing antibody response was comparable to that commonly seen in infected horses and humans. This may be explained by the early IFNα/β and/or γ response evident in the draining popliteal lymph node. Given this similarity to the human and equine disease, immunocompetent rabbits are, therefore, a valuable animal model for investigating various aspects of non-lethal WNV infections. PMID:26184326

  19. THE INFLUENCE OF INTRAVENOUSLY ADMINISTERED SURFACE-ACTIVE AGENTS ON THE DEVELOPMENT OF EXPERIMENTAL ATHEROSCLEROSIS IN RABBITS

    PubMed Central

    Kellner, Aaron; Correll, James W.; Ladd, Anthony T.

    1951-01-01

    A study was made of the relationship of blood lipids to the development of experimental atherosclerosis. Rabbits fed a diet containing cholesterol were found to develop hyperlipemia characterized by a great increase in blood cholesterol and a much lesser increase in blood phospholipids; after several weeks they manifested conspicuous atherosclerosis of the aorta, as has often been observed by others. Comparable rabbits fed the same diets containing added cholesterol were given in addition repeated intravenous injections of the surface-active agents Tween 80 and Triton A20; these animals developed hyperlipemia which was characterized by a great increase in blood cholesterol and an equivalent or even greater increase in phospholipids, and they had much less atherosclerosis than did the control rabbits fed cholesterol alone. In further experiments it was observed that repeated intravenous injections of Tween 80 did not result in resorption of previously induced atherosclerosis in rabbits. The findings are discussed in relation to the pathogenesis of natural and experimental atherosclerosis. PMID:14824410

  20. Intravascular photoacoustic imaging of gold nanorod-labeled atherosclerotic plaques

    NASA Astrophysics Data System (ADS)

    Yeager, Doug; Karpiouk, Andrei; Wang, Bo; Amirian, James; Sokolov, Konstantin; Smalling, Richard; Emelianov, Stanislav

    2012-02-01

    Combined intravascular photoacoustic (IVPA) and intravascular ultrasound (IVUS) imaging has been previously established as a viable means for imaging atherosclerotic plaques using both endogenous and exogenous contrast. In this study, IVUS/IVPA imaging of an atherosclerotic rabbit aorta following injection of gold nanorods (AuNR) with peak absorbance within the tissue optical window was performed. Ex-vivo imaging results revealed high photoacoustic signal from localized AuNR. Corresponding histological cross-sections and digital photographs of the artery lumen confirmed the presence of AuNR preferentially located at atherosclerotic regions and in agreement with IVPA signal. Furthermore, an integrated IVUS/IVPA imaging catheter was used to image the AuNR in the presence of luminal blood. The results suggest that AuNR allow for IVPA imaging of exogenously labeled atherosclerotic plaques with a comparatively low background signal and without the need for arterial flushing.

  1. New Zealand white rabbit as a nonsurgical experimental model for Salmonella enterica gastroenteritis.

    PubMed

    Hanes, D E; Robl, M G; Schneider, C M; Burr, D H

    2001-10-01

    Rabbits orally challenged with Salmonella enterica developed a dose-dependent diarrheal disease comparable to human salmonellosis. Viable Salmonella organisms recovered from the intestine and deep tissues indicate local and systemic infections. Therefore, results show that the rabbit can be used as a model for diarrheal disease and sequelae associated with salmonellosis.

  2. Efficacy of temperature-sensitive Guardix-SG for adhesiolysis in experimentally induced eyelid adhesion in rabbits.

    PubMed

    Sohn, Eun Jung; Ahn, Hee Bae; Roh, Mi Sook; Ryu, Won Yeol; Kwon, Yoon Hyung

    2013-01-01

    To determine the efficacy of a temperature-sensitive poloxamer/alginate mixture (Guardix-SG) for reducing adhesions after blepharoplasty in rabbit models. Thirty-six intact eyes of 18 rabbits were randomly designated to 2 groups, and primary blepharoplasty was performed on both the upper eyelids of the 18 rabbits. Sterile cotton soaked in 1 N NaOH was used to produce chemical tissue damage to experimentally induce eyelid adhesion, which was followed by adhesiolysis in 2 weeks. During adhesiolysis, Guardix-SG was applied to the OD of rabbits in the experimental group, while adhesiolysis alone was performed on the OS of rabbits in the control group. Both sides were compared by gross examination 1 day, 1 week, and 4 weeks after surgery, and the degrees of inflammation and fibrosis were examined with hematoxylin-eosin (H&E) and Masson's trichrome (MT) stains. The expression of α-smooth muscle actin (α-SMA) antibody was also immunohistochemically examined. The gross examinations performed after adhesiolysis yielded results that were not significantly different between the experimental and the control groups, and no prevalent complications, such as eyelid traction or distorted eyelids, were observed. One day (p = 0.028), 1 week (p = 0.028), and 4 weeks (p = 0.028) after surgery, the experimental group had a lower infiltration rate of inflammatory cells than the control group, as shown by H&E staining. The MT staining and α-SMA staining also showed that the collagen deposition and fibrosis (1 week, p = 0.059; 4 weeks, p = 0.034) and the degree of myofibroblast differentiation were significantly lower in the experimental group than in the controls (1 week, p = 0.027; 4 weeks, p = 0.024). The temperature-sensitive poloxamer/alginate mixture (Guardix-SG) decreased inflammation and fibrosis after blepharoplasty and histopathologically prevented the readhesion of secondary blepharoplasty in rabbit models. Therefore, additional clinical studies are needed for other

  3. Olive leaf extract facilitates healing of experimental cartilaginous injuries in rabbits.

    PubMed

    Gong, Dezheng; Geng, Chengyan; Jiang, Liping; Wang, Lihui; Yoshimuram, Hiroyuki; Zhong, Laifu

    2011-03-01

    We investigated the restorative effect of orally administered olive leaf extract (OLE) on experimentally produced cartilaginous injuries in rabbits. In total, three holes in the left stifle joint, including one in the medial trochlear ridge and two in the trochlear sulcus (proximal and distal) of articular cartilage, were prepared surgically using a drill. For the control group only tap water alone was administered daily, and for the OLE group a water-based solution of OLE (500 mg/kg/day) was administered daily. The injured areas were observed macroscopically and histologically at 3 weeks after the operation. The results indicate that OLE facilitated healing of the three holes and increased the weight of the biceps femoris muscle. Histological examination revealed that in the OLE group, matured cartilage tissues and connective tissues were mixed with regenerated or maturing cartilage tissues with massive proliferation in the injured parts, around which the proliferation of undifferentiated blast cells and the tissue with cartilage substrates were observed. The histological score of the OLE group was significantly lower than that of the control group. The percentage of proliferating cell nuclear antigen-positive cartilage cells in the OLE group was higher than in the control group. Mean density of the restored area observed with Safranin O staining was higher in the OLE group than in the control group. Therefore, OLE is effective for enhancing the healing of cartilaginous injuries. OLE may also have a beneficial effect of slowing and reducing the pathogenesis of degenerative joint diseases in humans.

  4. Diverse types of epineural conduits for bridging short nerve defects. An experimental study in the rabbit.

    PubMed

    Ignatiadis, Ioannis A; Yiannakopoulos, Christos K; Barbitsioti, Antonia D; Avram, Adrian M; Patralexis, Haralambos G; Tsolakis, Charilaos K; Papalois, Apostolos E; Xenakis, Theodoros H; Beris, Alexandros E; Soucacos, Panayiotis N

    2007-01-01

    In this study the process of peripheral nerve regeneration through an epineural flap conduit was examined using four groups of 126 New Zealand rabbits. There were three study groups (A, B, and C) and 1 control group (D). A 10-mm long sciatic nerve defect was bridged either with 3 variations of an epineural flap (Groups A, B, and C) or with a nerve autograft (Group D). Animals from all groups were examined 21, 42, and 91 days postoperatively to evaluate nerve regeneration employing light microscopy and immunocytochemistry. Nerve regeneration was studied in transverse sections at 3, 6, and 9 mm from the proximal stump. The gastrocnemius muscle contractility was also examined prior to euthanasia at 91 days postsurgery in all groups using electromyography. Immunohistochemical, histochemical and functional evaluation showed the presence of nerve regeneration resembling the control group D, especially in group A, where an advancement epineural flap was used. In this experimental model an epineural flap can be used to bridge a nerve defect successfully.

  5. Effects of flunixin meglumine on experimental tendon wound healing: A histopathological and mechanical study in rabbits.

    PubMed

    Behfar, Mehdi; Hobbenaghi, Rahim; Sarrafzadeh-Rezaei, Farshid

    2013-01-01

    Tendons are frequently targets of injury in sports and work. Whether nonsteroidal anti-inflammatory drugs (NSAIDs) have beneficial effects on tendon healing is still a matter of debate. This study was conducted to evaluate effects of flunixin meglumine (FM) on tendon healing after experimentally induced acute trauma. Twenty eight adult male New Zealand White rabbits were subjected to complete transection of deep digital flexor tendons followed by suture placement. Treatment group received intramuscular injection of FM for three days, and controls received placebo. Subsequently, cast immobilization was continued for two weeks. Animals were sacrificed four weeks after surgery and tissue samples were taken. The histological evaluations revealed improved structural characteristics of neotendon formation including fibrillar linearity, fibrillar continuity and neovascularization in treatment group compared to those of controls (p < 0.05). However, no significant differences were found between two groups in terms of epitenon thickness (p > 0.05). Mechanical evaluation revealed significant increase in load-related material properties including ultimate load, yield load, energy absorption and ultimate stress in treatment group compared to those of control group (p < 0.05). However, no statistically significant differences in terms of stiffness and ultimate strain were found (p > 0.05). The present study showed that intramuscular injection of FM resulted in improved structural and mechanical properties of tendon repairs and it could be an effective treatment for acute tendon injuries like severance and laceration.

  6. Effects of flunixin meglumine on experimental tendon wound healing: A histopathological and mechanical study in rabbits

    PubMed Central

    Behfar, Mehdi; Hobbenaghi, Rahim; Sarrafzadeh-Rezaei, Farshid

    2013-01-01

    Tendons are frequently targets of injury in sports and work. Whether nonsteroidal anti-inflammatory drugs (NSAIDs) have beneficial effects on tendon healing is still a matter of debate. This study was conducted to evaluate effects of flunixin meglumine (FM) on tendon healing after experimentally induced acute trauma. Twenty eight adult male New Zealand White rabbits were subjected to complete transection of deep digital flexor tendons followed by suture placement. Treatment group received intramuscular injection of FM for three days, and controls received placebo. Subsequently, cast immobilization was continued for two weeks. Animals were sacrificed four weeks after surgery and tissue samples were taken. The histological evaluations revealed improved structural characteristics of neotendon formation including fibrillar linearity, fibrillar continuity and neovascularization in treatment group compared to those of controls (p < 0.05). However, no significant differences were found between two groups in terms of epitenon thickness (p > 0.05). Mechanical evaluation revealed significant increase in load-related material properties including ultimate load, yield load, energy absorption and ultimate stress in treatment group compared to those of control group (p < 0.05). However, no statistically significant differences in terms of stiffness and ultimate strain were found (p > 0.05). The present study showed that intramuscular injection of FM resulted in improved structural and mechanical properties of tendon repairs and it could be an effective treatment for acute tendon injuries like severance and laceration. PMID:25568677

  7. The rabbit as an experimental and production animal: from genomics to proteomics.

    PubMed

    Miller, Ingrid; Rogel-Gaillard, Claire; Spina, Domenico; Fontanesi, Luca; de Almeida, Andre M

    2014-03-01

    The rabbit (Oryctolagus cuniculus) is an important animal species widely used for biomedical research purposes, meat production and as a pet animal. There are numerous biomedical and scientific applications that include important areas such as antibody production, muscle, eye and circulatory physiology. The use of proteomics has been limited when considering this species. The aim of this article is to provide a review on applications of proteomics to the rabbit species, including those that are most relevant and where rabbit is a key species: muscle and circulatory system physiology.

  8. Effects of glucosamine and risedronate alone or in combination in an experimental rabbit model of osteoarthritis

    PubMed Central

    2014-01-01

    Background The osteoarthritis (OA) treatment in humans and in animals is a major orthopaedic challenge because there is not an ideal drug for preserving the joint structure and function. The aim of this study was to assess the effects of the treatment with oral glucosamine and risedronate alone or in combination on articular cartilage, synovial membrane and subchondral bone in an experimental rabbit model of OA. Osteoarthritis was surgically induced on one knee of 32 New Zealand White rabbits using the contralateral as healthy controls. Three weeks later treatments were started and lasted 8 weeks. Animal were divided in four groups of oral treatment: the first group received only saline, the second 21.5 mg/kg/day of glucosamine sulfate, the third 0.07 mg/kg/day of risedronate; and the fourth group both drugs simultaneously at the same dosages. Following sacrifice femurs were removed and osteochondral cylinders and synovial membrane were obtained for its histological and micro-CT evaluation. Results Sample analysis revealed that the model induced osteoarthritic changes in operated knees. OA placebo group showed a significant increase in cartilage thickness respect to the control and inflammatory changes in synovial membrane; whereas subchondral bone structure and volumetric bone mineral density remained unchanged. All the treated animals showed an improvement of the cartilage swelling independent of the drug used. Treatment with glucosamine alone seemed to have no effect in the progression of cartilage pathology while risedronate treatment had better results in superficial fibrillation and in resolving the inflammatory changes of the tissues, as well as modifying the orientation of trabecular lattice. The combination of both compounds seemed to have additive effects showing better results than those treated with only one drug. Conclusions The results of this animal study suggested that glucosamine sulfate and risedronate treatment alone or in combination may be

  9. Effect of fish and krill oil supplementation on glucose tolerance in rabbits with experimentally induced obesity.

    PubMed

    Ivanova, Zhenya; Bjørndal, Bodil; Grigorova, Natalia; Roussenov, Anton; Vachkova, Ekaterina; Berge, Kjetil; Burri, Lena; Berge, Rolf; Stanilova, Spaska; Milanova, Anelia; Penchev, Georgi; Vik, Rita; Petrov, Vladimir; Georgieva, Teodora Mircheva; Bivolraski, Boycho; Georgiev, Ivan Penchev

    2015-10-01

    This study was conducted to investigate the effect of fish oil (FO) and krill oil (KO) supplementation on glucose tolerance in obese New Zealand white rabbits. The experiments were carried out with 24 male rabbits randomly divided into four groups: KO-castrated, treated with KO; FO-castrated, treated with FO; C-castrated, non-treated; NC-non-castrated, non-treated. At the end of treatment period (2 months), an intravenous glucose tolerance test (IVGTT) was performed in all rabbits. Fasting blood glucose concentrations in FO and KO animals were significantly lower than in group C. The blood glucose concentrations in FO- and KO-treated animals returned to initial values after 30 and 60 min of IVGTT, respectively. In liver, carnitine palmitoyltransferase 2 (Cpt2) and 3-hydroxy-3-methyl-glutaryl-CoA synthase 2 (Hmgcs2) genes were significantly increased in FO-fed rabbits compared with the C group. Acetyl-CoA carboxylase alpha (Acaca) expression was significantly reduced in both KO- and FO-fed rabbits. In skeletal muscle, Hmgcs2 and Cd36 were significantly higher in KO-fed rabbits compared with the C group. Acaca expression was significantly lower in KO- and FO-fed rabbits compared with the C group. The present results indicate that FO and KO supplementation decreases fasting blood glucose and improves glucose tolerance in obese New Zealand white rabbits. This could be ascribed to the ameliorated insulin sensitivity and insulin secretion and modified gene expressions of some key enzymes involved in β-oxidation and lipogenesis in liver and skeletal muscle.

  10. Experimental study on the toxicity of povidone-iodine solution in brain tissues of rabbits

    PubMed Central

    Li, Shu-Hua; Wang, Yu; Gao, Hai-Bin; Zhao, Kun; Hou, Yu-Chen; Sun, Wei

    2015-01-01

    Objective: To determine whether Povidone-iodine was toxic to brain tissues by rinsing the cerebral cortex of New Zealand rabbits with Povidone-iodine Solution of different concentrations. Methods: 12 New Zealand rabbits were randomly divided into 4 groups (Group A, B, C and D, 3 rabbits each group). In each group, the left cerebral cortex of rabbits was rinsed with physiological saline after the craniotomy; in Group A and B, the right cerebral cortex of rabbits was also locally rinsed with Povidone-iodine Solution (0.01%), in Group C and D, the right cerebral cortex of rabbits was also locally rinsed with Povidone-iodine Solution (0.05%). In Group A and C, the rabbits were sacrificed at D3 after the operation, and the brain was taken out; and in Group B and D, the rabbits were sacrificed at D7 after the operation, and the brain was taken out. Under the optical and electron microscope, the change in micro-structure of brain tissues was observed in each group. Results: In each group, there was no epilepsy or paralysis during and after the operation. At the treatment side of physiological saline, there was no significant cell damage in the local brain tissues. At the treatment side of Povidone-iodine Solution, there was no cell apoptosis or degeneration in the local brain tissues. Conclusion: The Povidone-iodine Solution (0.05% and 0.01%) was toxic to brain tissues, with a more obvious damage of brain tissues for the former concentration. The histological sign was more serious at D7 than that at D3. PMID:26628968

  11. [Experimental study of TGF-β2 antisense oligonucleotide on inhibiting corneal scar hyperplasia in rabbits].

    PubMed

    Zheng, Guang-ying; Hao, Li-li; Wang, Rui-na; Lian, Yuan-jun; Tan, Nan

    2013-02-01

    To investigate the influence of TGF-β2 antisense oligonucleotide (ASON) on preventing corneal scar hyperplasia in rabbits and to provide experimental evidence for its clinical application. It was an experimental study. One hundred and ninety two New Zealand white rabbits were randomly divided into 4 groups (groups A, B, C and D). Corneal injury models were established in all groups. There were 48 experimental animals in each group. TGF-β2 ASON was dropped into right eyes in group A, dexamethasone was dropped into right eyes in group B, deionized water was dropped into right eyes in group C and nothing was dropped into right eyes in group D after the operation. The corneas were surgically removed and assessed by hematoxylin eosin (HE) staining, immunohistochemical study and real time PCR at four different time points (4 d, 7 d, 14 d and 28 d) after surgery. HE staining: at the same time point, fibroblasts in the groups A and B were significantly fewer than that in the groups C and D, the difference was statistically significant (P < 0.05), but there was no significant difference between groups A and B or groups C and D. Immunohistochemical observation found that the expression of α-smooth muscle actin (α-SMA) positive fibroblasts could be observed by the 4th day (9.44 ± 0.47/HP), reached a climax by the 7th day (12.50 ± 0.81/HP), and returned to the baseline levels by the 14th day (0.85 ± 0.43/HP) in the group A, which was similar to that in the group B (9.49 ± 0.95, 12.42 ± 0.70, 0.86 ± 0.79/HP) at the same time point (P > 0.05), but it was significantly fewer than that in the group C(20.14 ± 0.78, 18.19 ± 1.28, 4.87 ± 0.58/HP) and group D(20.21 ± 0.92, 18.25 ± 1.39, 5.00 ± 2.217/HP), which was statistical significant (P < 0.05). The staining intensity of fibronectin (FN) in groups A and B was significantly weaker than that in groups C and D. Real time PCR analysis showed that at each time point, the expression of TGF-β2 mRNAs in groups A and B was

  12. Lymphatic vessels: an emerging actor in atherosclerotic plaque development.

    PubMed

    Kutkut, Issa; Meens, Merlijn J; McKee, Thomas A; Bochaton-Piallat, Marie-Luce; Kwak, Brenda R

    2015-01-01

    Atherosclerosis is a chronic inflammatory disease of large- to medium-sized arteries and is the main underlying cause of death worldwide. The lymphatic vasculature is critical for processes that are intimately linked to atherogenesis such as the immune response and cholesterol metabolism. However, whether lymphatic vessels truly contribute to the pathogenesis of atherosclerosis is less clear despite increasing research efforts in this field. PubMed and Ovid MEDLINE databases were searched. In addition, key review articles were screened for relevant original publications. Current knowledge about lymphatic vessels in the arterial wall came from studies that examined the presence and location of such vessels in human atherosclerotic plaque specimens, as well as in a variety of arteries in animal models for atherosclerosis (e.g. rabbits, dogs, rats and mice). Generally, three experimental approaches have been used to investigate the functional role of plaque-associated lymphatic vessels; experimental lymphostasis was used to investigate lymphatic drainage of the arterial wall, and more recently, studies with genetic interventions and/or surgical transplantation have been performed. Lymphatic vessels seem to be mostly present in the adventitial layer of the arterial walls of animals and humans. They are involved in reverse cholesterol transport from atherosclerotic lesions, and arteries with a dense lymphatic network seem naturally protected against atherosclerosis. Lymphangiogenesis is a process that is an important part of the inflammatory loop in atherosclerosis. However, how augmenting or impeding the distribution of lymphatic vessels impacts disease progression remains to be investigated in future studies. © 2014 Stichting European Society for Clinical Investigation Journal Foundation.

  13. Can a graft be placed over a flap in complex hypospadias surgery? An experimental study in rabbits

    PubMed Central

    de Mattos, Ricardo Marcondes; de Araújo, Sérgio R.R.; Quitzan, Juliany Gomes; Leslie, Bruno; Bacelar, Herick; Parizi, João Luiz Gomes; Caetano Martins, Gustavo Marconi; da Cruz, Marcela Leal; Macedo, Antonio

    2016-01-01

    ABSTRACT Purpose: To develop a rabbit experimental study to test the hypothesis that surgical repair of hypospadias with severe ventral curvatures might be completed in one stage, if a graft, such as buccal mucosa, could be placed over the tunica vaginalis flap used in corporoplasty for ventral lengthening, with the addition of an onlay preputial island flap to complete the urethroplasty. Materials and methods: The experimental procedure with rabbits included a tunica vaginalis flap for reconstruction of the corpora after corporotomy, simulating a ventral lengthening operation. A buccal mucosa graft was placed directly on top of the flap, and the urethroplasty was completed with an onlay preputial island flap. Eight rabbits were divided into 4 groups, sacrificed at 2, 4, 8 and 12 weeks postoperatively, and submitted to histological evaluation. Results: We observed a large number of complications, such as fistula (75%), urinary retention (50%) and stenosis (50%). There were two deaths related to the procedure. Histological evaluation demonstrated a severe and persistent inflammatory reaction. No viable tunica vaginalis or buccal mucosa was identified. Conclusions: In this animal model, the association of a buccal mucosa graft over the tunica vaginalis flap was not successful, and resulted in complete loss of both tissues. PMID:27649106

  14. [Experimental research on the prevention of rabbit postoperative abdominal cavity adhesion with PLGA membrane].

    PubMed

    Pang, Xiubing; Pan, Yongming; Hua, Fei; Sun, Chaoying; Chen, Liang; Chen, Fangming; Zhu, Keyan; Xu, Jianqin; Chen, Minli

    2015-02-01

    The aim of this paper is to explore the prevention of rabbit postoperative abdominal cavity adhesion with poly (lactic-co-glycotic acid) (PLGA) membrane and the mechanism of this prevention function. Sixty-six Japanese white rabbits were randomly divided into normal control group, model control group and PLGA membrane group. The rabbits were treated with multifactor methods to establish the postoperative abdominal cavity adhesion models except for those in the normal control group. PLGA membrane was used to cover the wounds of rabbits in the PLGA membrane group and nothing covered the wounds of rabbits in the model control group. The hematologic parameters, liver and kidney functions and fibrinogen contents were detected at different time. The rabbit were sacrificed 1, 2, 4, 6, 12 weeks after the operations, respectively. The adhesions were graded blindly, and Masson staining and immunohistochemistry methods were used to observe the proliferation of collagen fiber and the expression of transforming growth factor β1 (TGF-β1) on the cecal tissues, respectively. The grade of abdominal cavity adhesion showed that the PLGA membrane-treated group was significant lower than that in the model control group, and it has no influence on liver and kidney function and hematologic parameters. But the fibrinogen content and the number of white blood cell in the PLGA membrane group were significant lower than those of model control group 1 week and 2 weeks after operation, respectively. The density of collagen fiber and optical density of TGF-β1 in the PLGA membrane group were significant lower than those of model control group. The results demonstrated that PLGA membrane could be effective in preventing the abdominal adhesions in rabbits, and it was mostly involved in the reducing of fibrinogen exudation, and inhibited the proliferation of collagen fiber and over-expression of TGF-β1.

  15. Epitope-focused peptide immunogens in human use adjuvants protect rabbits from experimental inhalation anthrax.

    PubMed

    Oscherwitz, Jon; Feldman, Daniel; Yu, Fen; Cease, Kemp B

    2015-01-09

    Anthrax represents a formidable bioterrorism threat for which new, optimized vaccines are required. We previously demonstrated that epitope-focused multiple antigenic peptides or a recombinant protein in Freund's adjuvant can elicit Ab against the loop neutralizing determinant (LND), a cryptic linear neutralizing epitope in the 2ß2-2ß3 loop of protective antigen from Bacillus anthracis, which mediated protection of rabbits from inhalation challenge with B. anthracis Ames strain. However, demonstration of efficacy using human-use adjuvants is required before proceeding with further development of an LND vaccine for testing in non-human primates and humans. To optimize the LND immunogen, we first evaluated the protective efficacy and immune correlates associated with immunization of rabbits with mixtures containing two molecular variants of multiple antigenic peptides in Freunds adjuvant, termed BT-LND(2) and TB-LND(2). TB-LND(2) was then further evaluated for protective efficacy in rabbits employing human-use adjuvants. Immunization of rabbits with TB-LND(2) in human-use adjuvants elicited protection from Ames strain spore challenge which was statistically indistinguishable from that elicited through immunization with protective antigen. All TB-LND(2) rabbits with any detectable serum neutralization prior to challenge were protected from aerosolized spore exposure. Remarkably, rabbits immunized with TB-LND(2) in Alhydrogel/CpG had significant anamnestic increases in post-challenge LND-specific Ab and neutralization titers despite little evidence of spore germination in these rabbits. An LND-specific epitope-focused vaccine may complement PA-based vaccines and may represent a complementary stand-alone vaccine for anthrax. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Cell death during the postnatal morphogenesis of the normal rabbit kidney and in experimental renal polycystosis.

    PubMed Central

    García-Porrero, J A; Ojeda, J L; Hurlé, J M

    1978-01-01

    We have studied, by means of optic and electron microscopy, the normal and abnormal cell death that takes place during the postnatal morphogenesis of rabbit kidney, and in the experimental renal polycystosis produced by methylprednisolone acetate. In the normal kidney intertubular cell death can be observed during the first 20 days of the postnatal development. However, cell death in the normal metanephric blastema is a very rare event. In the polycystic kidney numerous dead cells can be seen between the third and forty eighth days after injection. The topography and morphology of the dead cells depend on the stage in the evolution of the disease. In the 'stage of renal immaturity', dying and dead cells are present in the nephrogenic tissue, in the dilating collecting tubules and in the intertubular spaces. In this stage the cellular pathology is essentially nuclear. In the stage of tubular cysts, the dead cells are mostly located in the walls of cysts, with some dead cells, but mostly cellular debris in their lumina. At this stage the cellular pathology is basically cytoplasmic. The dead cells are eventually digested by what appear to be phagocytes of tubular epithelial origin. It is suggested that cell death is an important factor in the evolution of the lesions of renal polycystosis induced by corticosteroids, and probably in the initiation of the pathological process as well. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 Fig. 15 Fig. 16 Fig. 17 Fig. 18 Fig. 19 PMID:670065

  17. The effect of butyric acid with autogenous omental graft on healing of experimental Achilles tendon injury in rabbits

    PubMed Central

    Jahani, S; Moslemi, H. R.; Dehghan, M. M.; Sedaghat, R; Mazaheri Nezhad, R; Rezaee Moghaddam, D

    2015-01-01

    In this study, the role of local injection of butyric acid (BA) with autogenous omental graft was evaluated in healing of experimental Achilles tendon injury in rabbits. Nine adult male New Zealand rabbits were anesthetized and a partial thickness tenotomy was created on both hindlimbs. In treated group, omental graft was secured in place using BA soaked polygalactin 910 suture. In control group, the graft was sutured without BA. Butyric acid and normal saline were injected daily to treatment and control groups for three days, respectively. Based on the findings, on day 15 after injury, the tendon sections showed that healing rate in BA treated group was higher than that in control group. Furthermore, at days 28 and 45, comparison between BA treated and control groups demonstrated that BA increased the healing rate but with no significance. In summary, results of this study show that application of BA with autogenous omental graft can improve healing process of damaged Achilles tendon. PMID:27175160

  18. Experimental infection of rabbits (Oryctolagus cuniculus) with Brucella suis biovar 1 isolated from wild hares (Lepus europaeus).

    PubMed

    Fort, Marcelo; Baldone, Valeria; Fuchs, Lumila; Giménez, Hugo; Rojas, María; Breccia, Javier D; Oyhenart, Jorge

    2012-05-04

    Brucella suis biovar 1 is the causative agent of brucellosis in several domestic and wild animals and it is a common agent of human brucellosis. European hares (Lepus europaeus) have been shown to be infected by B. suis biovar 1 and the transmission to other animals has been suggested. In this work, experimental rabbits (Cuniculus orictolagus) were infected with B. suis biovar 1 isolated from wild hares. Infected rabbits showed high serological response in 2 weeks after discharge and typical granulomatous lesions (2mm diameter) were found in liver, spleen and kidneys after 50 days. B. suis biovar 1 was cultured from the lesion of the organs mentioned above as well as from urine, placenta and fetuses. These data suggest that hares are a potential source for horizontal transmission of B. suis biovar 1 to other mammalians.

  19. MR-Guided PTA in Experimental Bilateral Rabbit Renal Artery Stenosis and MR Angiography Follow-Up Versus Histomorphometry

    SciTech Connect

    Le Blanche, Alain-Ferdinand; Rossert, Jerome; Wassef, Michel; Levy, Bernard; Bigot, Jean-Michel; Boudghene, Frank

    2000-09-15

    Purpose: To assess in vivo 1) MR-guided percutaneous transluminal renal angioplasty (PTRA) in experimental bilateral rabbit renal artery stenosis (RAS); 2) postprocedural follow-up by gadolinium-enhanced MR angiography versus histomorphometry.Methods: Fifteen male NZW rabbits of mean weight 4.0 kg (range 3.5-4.2 kg) underwent bilateral RAS induction by combined overdilation-deendothelialization with a gadolinium-filled balloon, passively MR-guided by the artifact of a 0.014-inch guidewire. After 4 weeks the rabbits were randomized into two groups: group A (n = 8) underwent right-sided PTRA for treatment of RAS, group B (n = 7) underwent left-sided PTRA. After another 4 weeks the rabbits were killed to assess by histomorphometry recurrent stenosis and contralateral induction injury stenosis lesions. Each step was preceded by gadolinium-enhanced three-dimensional MR angiography, and the cortex-to-aorta (C/A) signal intensity ratio was calculated.Results: RAS induction was successful in all cases. Fourteen arteries developed restenosis and 13 only initial stenosis. MR-guided PTRAs were feasible in 22 arteries (73%). For a successful catheterization of the ostium (20 arteries, 66% success rate), 10-25 steps were required. Five to eight steps were required for balloon localization and inflation for each PTRA. The restenosis effect was reflected by a 16% (12%-27%) decrease in C/A values on MR angiograms (p < 0.05).Conclusion: MR guidance and MR angiography represent a feasible, less invasive alternative for performing and assessing experimental PTRA in RAS.

  20. Experimental Infection of New Zealand White Rabbits (Oryctolagus cuniculi) with Leporid herpesvirus 4

    PubMed Central

    Sunohara-Neilson, Janet R; Brash, Marina; Carman, Susy; Nagy, Éva; Turner, Patricia V

    2013-01-01

    Leporid herpesvirus 4 (LHV4) is a novel alphaherpesvirus recently identified in domestic rabbits (Oryctolagus cuniculi). Little is known about the pathogenesis or time course of disease induced by this virus. We therefore intranasally inoculated 22 female New Zealand white rabbits with 8.4 × 104 CCID50 of a clinical viral isolate. Rabbits were monitored for clinical signs, viral shedding in oculonasal secretions, and development and persistence of serum antibodies. Rabbits were euthanized at 3, 5, 7, 14, and 22 d postinfection (dpi) to evaluate gross and microscopic changes. Clinical signs were apparent between 3 to 8 dpi, and included oculonasal discharge, respiratory distress, and reduced appetite, and viral shedding occurred between 2 and 8 dpi. Seroconversion was seen at 11 dpi and persisted to the end of the study (day 22). Severe necrohemorrhagic bronchopneumonia and marked pulmonary edema were noted by 5 dpi and were most severe at 7 dpi. Pulmonary changes largely resolved by 22 dpi. In addition, multifocal splenic necrosis was present at 5 dpi and progressed to submassive necrosis by 7 dpi. Eosinophilic herpesviral intranuclear inclusion bodies were detected in the nasal mucosa, skin, spleen, and lung between 3 to 14 dpi. LHV4 is a pathogen that should be considered for rabbits that present with acute respiratory disease. LHV4 infection can be diagnosed based on characteristic microscopic changes in the lungs and spleen and by virus isolation. Serum antibody levels may be used to monitor viral prevalence in colonies. PMID:24210019

  1. Experimental infection of New Zealand white rabbits (Oryctolagus cuniculi) with Leporid herpesvirus 4.

    PubMed

    Sunohara-Neilson, Janet R; Brash, Marina; Carman, Susy; Nagy, Eva; Turner, Patricia V

    2013-10-01

    Leporid herpesvirus 4 (LHV4) is a novel alphaherpesvirus recently identified in domestic rabbits (Oryctolagus cuniculi). Little is known about the pathogenesis or time course of disease induced by this virus. We therefore intranasally inoculated 22 female New Zealand white rabbits with 8.4 × 10(4) CCID50 of a clinical viral isolate. Rabbits were monitored for clinical signs, viral shedding in oculonasal secretions, and development and persistence of serum antibodies. Rabbits were euthanized at 3, 5, 7, 14, and 22 d postinfection (dpi) to evaluate gross and microscopic changes. Clinical signs were apparent between 3 to 8 dpi, and included oculonasal discharge, respiratory distress, and reduced appetite, and viral shedding occurred between 2 and 8 dpi. Seroconversion was seen at 11 dpi and persisted to the end of the study (day 22). Severe necrohemorrhagic bronchopneumonia and marked pulmonary edema were noted by 5 dpi and were most severe at 7 dpi. Pulmonary changes largely resolved by 22 dpi. In addition, multifocal splenic necrosis was present at 5 dpi and progressed to submassive necrosis by 7 dpi. Eosinophilic herpesviral intranuclear inclusion bodies were detected in the nasal mucosa, skin, spleen, and lung between 3 to 14 dpi. LHV4 is a pathogen that should be considered for rabbits that present with acute respiratory disease. LHV4 infection can be diagnosed based on characteristic microscopic changes in the lungs and spleen and by virus isolation. Serum antibody levels may be used to monitor viral prevalence in colonies.

  2. Atheroprotective effects of pure tocotrienol supplementation in the treatment of rabbits with experimentally induced early and established atherosclerosis

    PubMed Central

    Rahman, Thuhairah Abdul; Hassim, Noor Faezah; Zulkafli, Nurmazni; Muid, Suhaila; Kornain, Noor Kaslina; Nawawi, Hapizah

    2016-01-01

    Background Atherosclerosis is the main cause of coronary artery disease -related deaths worldwide. The atheroprotective properties of pure tocotrienols (T3) in the absence of alpha-tocopherol (α-TCP) in vitamin E has not been extensively examined. Aim To determine the atheroprotective properties of T3 in early and established atherosclerosis rabbits. Methods Thirty New Zealand white rabbits were divided into two groups, B1 and B2 which represent early [fed 1% high cholesterol diet (HCD) for 2 weeks] and established (fed 1% HCD for 8 weeks) atherosclerosis. Each group was subdivided into three intervention arms: 1) T3–4 mg/kg, 2) T3–15 mg/kg and 3) vehicle without T3 (T3 negative) for 8 weeks. Serial fasting blood samples were obtained for lipid profile, and whole lengths of aorta were used to determine tissue markers of endothelial activation, inflammation and plaque stability. Results In B1, atherosclerotic lesion in T3–4 mg/kg group was significantly reduced (p=0.008), while aortic tissue expression of vascular cellular adhesion molecule 1 (VCAM-1), interleukin-6 (IL-6) and matrix metalloproteinase (MMP-12) was reduced in T3–4 mg/kg compared to T3-negative rabbits group (0.2±0.1 vs. 28.5±3.1%; 3.0±1.6 vs. 14.0±1.7%; and 5.2±2.2 vs. 27.7±0.8%, respectively, p<0.05). T3–15 mg/kg group showed reduction in VCAM-1, E-selectin, IL-6 and MMP-12 (3.9±1.9 vs. 28.5±3.1%; 10.3±0.5 vs. 59.8±8.5%; 2.6±1.7 vs. 14.0±1.7%; and 16.2±3.2 vs. 27.7 0.8%, respectively, p<0.05). In B2, T3–4 mg/kg group reduced aortic tissue expression of intercellular adhesion molecule 1 (ICAM-1), E-selectin, IL-6, MMP-12 and MMP-9 compared to T3-negative rabbits group (29.9±2.4 vs. 55.3±1.3%; 26.7±1.5 vs. 60.5±7.6%; 15.7±0.7 vs. 27.7±4.8%; 34.8±2.7 vs. 46.5±3.4%; and 25.89±3.9 vs. 45.9±1.7%, respectively, p<0.05). T3–15 mg/kg group showed reduced VCAM-1, ICAM-1, E-selectin, IL-6, MMP-12 and MMP-9 (20.5±3.3 vs. 35.6±2.5%; 24.9±1.3 vs. 55.3±1.3%; 29.9±6.7 vs

  3. Pharmacokinetics of norethisterone and levonorgestrel in experimental iron deficiency anemia in rabbits.

    PubMed

    Sivakumar, B; Nair, K M; Prasad, K V; Rao, B S

    1985-11-01

    Mild-moderate anemia (hemoglobin, 10-12 g/100 ml) was induced in eight female rabbits by feeding a purified diet with low iron content over a period of 4 months and it could be maintained for a further period of 7 months. Nine control animals received the same diet supplemented with iron. Pharmacokinetics of intravenously administered contraceptive steriods, norethindrone and levonorgestrel, were determined in both control and anemic rabbits at the end of 150 and 171 days, respectively. No significant alterations were observed in the disposition of these steroids in deficient rabbits as compared to controls, indicating that mild-moderate forms of iron deficiency anemia may not influence the metabolic handling of either norethindrone or levonogestrel.

  4. The effects of low-dose radiotherapy on fresh osteochondral allografts: An experimental study in rabbits.

    PubMed

    Gönç, Uğur; Çetinkaya, Mehmet; Atabek, Mesut

    2016-10-01

    The aim of this study was to investigate the effects of low-dose fractionated radiotherapy on cartilage degeneration after distal femoral fresh massive osteochondral allograft transplantation. Twenty-four New Zealand White rabbits were divided into three groups of 8 rabbits each. All rabbits underwent distal femoral medial condyle fresh massive osteochondral allograft transplantation from California rabbits. The group 1 underwent transplantation without any preliminary process. The group 2 underwent fractionated local radiotherapy of 100 cGy for five days starting on the transplantation day. The group 3 included the rabbits to which the grafts transplanted after radiating in vitro by a single dose radiation of 1500 cGy. The hosts were sacrificed twelve weeks later. Anteroposterior and lateral radiographs were taken. Synovial tissue, cartilaginous tissue, and subchondral bone were assessed histopathologically. Nonunion was present in three cases of group 2 and one of group 3 in which cartilage degeneration was more severe. Synovial hypertrophy and pannus formation were more obvious in non-radiated rabbits. Hypocellularity and necrosis of the subchondral bone were rare in group 2. More cartilage tissue impairment was present in group 3 compared to group 1. In osteochondral massive allograft transplantations, the immune reaction of the host could be precluded with radiotherapy, and the side-effects can be prevented by low-dose fractionated regimen. The total dose of fractionated radiotherapy for an immune suppression should be adjusted not to damage the cartilage tissue, but to avoid articular degeneration in the long term. Copyright © 2016 Turkish Association of Orthopaedics and Traumatology. Production and hosting by Elsevier B.V. All rights reserved.

  5. [The effect of low molecular heparin and urokinase on MCP-1 of acute experimental pulmonary embolism in rabbits].

    PubMed

    Yu, Hongzhi; Wu, Qi; Wu, Junping; Sun, Xin; Du, Zhongzhen; Li, Li; Wu, Qian

    2014-06-01

    To evaluate effect the of thrombolytic (urokinase, UK) and anticoagulant agent (low-molecular-weight heparin, LMWH) on the pulmonary injury of rabbits with acute pulmonary embolism (PE) by assaying monocyte chemoattractant protein-1 (MCP-1). Rabbit models with PE were established by transfusing autologous blood clots on 60 healthy male Japanese white rabbits. Experimental PE rabbits were randomly divided into 3 groups:normal saline (NS) group (n = 18) , LMWH group (n = 18) and UK group (n = 18), and other 18 rabbits underwent sham operations as SHAM group (n = 18). Each group was divided into 3 subgroups based on 2 days (day 2), 4 days (day 4), and 14 days (day 14) after therapies. Arterial blood gas analysis was measured. MCP-1 levels in lung tissue and blood were assayed with ELISA at various times (day 2, day 4 and day 14 ). Fixed sections were stained with trichrome for intimal hyperplasia determination. The overall rate of success for making PE rabbit models was 90% (54/60), which was not affected by treatment. Compared with NS group, P(A-a)O2 significantly decreased in UK group. Compared with NS group, MCP-1 levels in lung tissue significantly decreased in LMWH group on day 4 [(33 ± 9) ng/L vs (48 ± 5) ng/L, P < 0.05] and day 14 [(30 ± 11) ng/L vs (41 ± 4) ng/L, P < 0.05]; MCP-1 levels in serum on day 14 also significantly decreased in LMWH group [(36 ± 10) ng/L vs (51 ± 5) ng/L, P < 0.05]. Compared with NS group, MCP-1 levels in lung tissue significantly decreased in UK group on day 2 and 4 [Day 2: (34 ± 8) ng/L vs (50 ± 4) ng/L, P < 0.05; Day 4: (29 ± 7) ng/L vs (48 ± 5) ng/L, P < 0.05]; MCP-1 levels in serum on day 2 and day 4 also significantly decreased in UK group [Day 2: (44 ± 3) ng/L vs (48 ± 3) ng/L, P < 0.05; Day 4: (44 ± 4) ng/L vs (53 ± 1)ng/L, P < 0.05]. UK treatment may rapidly improve V/Q ratio and decrease MCP-1 levels in lung tissue or serum, but it can not inhibit persistent inflammation. LMWH can decrease MCP-1 levels in lung

  6. Comparison between two different experimental models of osteoarthritis in rabbits. Intra-articular collagenase injection and anterior cruciate ligament transection.

    PubMed

    Hermeto, Larissa Correa; Rossi, Rafael De; Jardim, Paulo Henrique de Affonseca; Santana, Aureo Evangelista; Rinaldi, Jaqueline de Carvalho; Justulin, Luis Antonio

    2016-09-01

    To compare two different experimental models of osteoarthritis in rabbits: intra-articular collagenase injection and anterior cruciate ligament transection. Ten adult rabbits were randomly divided in two groups: COLL (collagenase group) and ACLT (anterior cruciate ligament transection). The COLL group was treated with 0.5 ml collagenase solution (2mg collagenase/0.5 ml sterile PBS), and the ACTL group was subjected to anterior cruciate ligament. After six and twelve weeks, respectively, the animals in the COLL and ACTL groups were euthanized. The gross appearance and histological examinations conducted in the cartilage articular surface was blindly scored according to the criteria developed by Yoshimi et al. (1994) and Mankin et al. (1971), respectively. The gross morphologic observation, macroscopic score and histological examinations have demonstrated that the ACTL group presented the highest scores, and lesions more severe than those in the COLL group. Both methods, anterior cruciate ligament transection and collagenase, applied to the stifle joint of the rabbits have effectively induced degenerative changes in the cartilage tissue, through statistically significant analysis (p≤0.05). The ACTL method has presented more severe lesions.

  7. An Experimental Study on Botulinum Toxin Type A for the Treatment of Excessive Secretion after Submandibular Gland Transplantation in Rabbits

    PubMed Central

    Lin, Bo; Wang, Kan

    2016-01-01

    Objectives. To investigate whether botulinum toxin type A (BTXA) could control excessive secretion after submandibular gland (SMG) transplantation in rabbits and its possible mechanisms. Methods. A new SMG transplantation model was established in rabbit. 30 successfully constructed models were randomly assigned to five groups including control group and four experimental groups. Secretion outputs were used to analyze the effect of BTXA injection on excessive secretion. Hematoxylin and eosin (HE) staining, transmission electron microscopy (TEM), Western blot, and immunofluorescence were performed to analyze its possible mechanisms. Results. After BTXA injection, a significant decrease of excessive secretion after SMG transplantation was found in 2 and 4 weeks groups, but no significant effect on 12 and 24 weeks groups. HE and TEM results showed that BTXA led to morphological and ultrastructural changes of acinar cells of transplanted SMG. Western blot results suggested that BTXA decreased the aquaporin-5 (AQP5) protein expression after BTXA injection for 2 and 4 weeks. Immunofluorescence results showed that AQP5 protein was mainly expressed in the cytoplasm after BTXA injection for 2 and 4 weeks, which might indicate that BTXA promoted AQP5 expression from the cell membrane to cytoplasm. Conclusion. BTXA could effectively control excessive secretion after SMG transplantation in rabbits. PMID:27840738

  8. Effect of captopril on serum lipid levels and cardiac mitochondrial oxygen consumption in experimentally-induced hypercholesterolemia in rabbits.

    PubMed

    Kojic, Z; Gopcevic, K; Marinkovic, D; Tasic, G

    2011-01-01

    Angiotensin converting enzyme inhibitors are widely used in therapy of cardiovascular diseases. However, the consensus on effects of these inhibitors in control of myocardial oxygen consumption during the process of experimental hypercholesterolemia and under the condition of endothelial dysfunction has not been reached. Here we examined effects of captopril, an angiotensin converting enzyme inhibitor, on serum lipid levels and oxygen consumption rate in mitochondria isolated from heart of rabbits treated by hypercholesterolemic diet. During the twelve-week period, the Chinchilla male rabbits were daily treated by saline (controls); 1 % cholesterol diet; 5 mg/kg/day captopril or 1 % cholesterol + 5 mg/kg/day captopril. Total- and high-density lipoprotein cholesterol and triglyceride in serum were measured spectrophotometrically. The left ventricle mitochondrial fraction was isolated and myocardial oxygen consumption was measured by Biological Oxygen Monitor. Mitochondria isolated from hearts of rabbits exposed to hypercholesterolemic diet showed significantly reduced respiration rates (state 3 and state 4) with altering adenosine diphosphate/oxygen ratio, whereas the respiratory control ratio was not affected when compared to controls. Mitochondria from cholesterol/captopril-treated animals showed significantly reduced respiration rates without altering adenosine diphosphate/oxygen ratio index or respiratory control ratio. Although captopril did not exert the favorable effect on serum lipid levels in cholesterol-treated animals, it restored the mitochondrial oxygen consumption. Further studies should be performed to define the underlying physiological and/or pathophysiological mechanisms and clinical implications.

  9. [Experimental study on treatment of rabbits optic nerve injury with Caspase-3 inhibitor z-DEVD-fmk].

    PubMed

    Zhang, Wei; Yu, Jin-guo; Wang, Xing; Shen, Zhan-sheng; Zhang, Jing-kai; Yan, Hua

    2010-12-01

    To observe the effects of caspase-3 inhibitor z-DEVD-fmk on optic nerve injury of rabbits. It was an experimental study. Two to three month-old rabbits were used in this study. The rabbit model of optic nerve injury was created by fluid percussion brain injury device (FPI). DMSO (5 µl 2% solution) was injected intravitreally to the left eyes (control group). Caspase-3 inhibitor z-DEVD-fmk (5 µl) was injected intravitreally to the right eyes (experimental group). Flash-visual evoked potential (F-VEP) and histopathological examination of the retina were used to check the variations in optic nerve injury at 1, 4, 7, 10, 14, and 21 days after the treatment. Immunohistochemistry was used to detect the expression of caspase-3 in the retina. T-test, variance analysis, q-test and linear correlation analysis were used to analyze these data. At the 7th day after treatment, the latency of F-VEP P1 in experimental group was shorter than that in the control group [(90.50±7.61) ms vs (113.59±12.92) ms, t=4.060, P<0.05] and the number of retinal ganglion cells (RGC) in the experimental group was greater than that in the control group (237.62±8.50 vs 207.03±11.04, t=-5.843, P<0.05). Both of these trends continued to the 21st day after treatment [(67.97±7.93) ms vs. (134.22±8.50) ms, t=13.950, P<0.05; 156.32±8.45 vs. 207.13±12.21, t=-10.307, P<0.05]. The absorbency (A) of caspase-3 in the experimental group (0.396±0.023) was lower than that in the control group (0.458±0.024) and this difference was statistically significant (t=6.200, P<0.05) at the 7th day after treatment. The latency of F-VEP P1 and the absorbency of caspase-3 in the retina were positively correlated with each other (r=0.95, P<0.05). z-DEVD-fmk is effective in treating rabbit optic nerve injury by inhibiting the expression of caspase-3 in the retina. It can promote the recovery of optic nerve function.

  10. Role of mechanical compression on bone regeneration around a particulate bone graft material: an experimental study in rabbit calvaria.

    PubMed

    Romanos, Georgios E; Delgado-Ruiz, Rafael A; Gómez-Moreno, Gerardo; López-López, Patricia J; Mate Sanchez de Val, Jose E; Calvo-Guirado, Jose Luis

    2015-04-12

    This experimental study was designed to analyze the effect of different compressive forces on the bone regeneration around a particulate bone graft material. Eighty 6-mm-diameter defects were created in the calvaria of 20 New Zealand rabbits (4 defects per rabbit calvaria). All the defects were filled with particles of synthetic bone. Two standardized compressive forces were then applied, 4.1 g to half the defects (Test A) and 8.2 g to the other half (Test B), all for 1 min. The graft sites were allowed to heal for 6 weeks, after which the rabbits were euthanized. The calvarium vault of each animal was extracted, radiographed, and prepared for histomorphometric analysis. The percentage of defect fill, bone density, new bone formation, and residual bone graft material were recorded, and the results were subjected to statistical analysis. Histological evaluation found that defect closure among the Test A (lower compression) group ranged from 38.34 (95% lower CI) to 55.8 (95% upper CI) (mean 47 ± 8.5%), while among the Test B group (higher compression), it ranged from 81.26 (95% lower CI) to 95.32 (mean 88 ± 7.3%). Significantly more closure was achieved for the Test B group (P < 0.05). Histomorphometric comparison of the two groups found significantly more new bone formation, higher bone density, and a higher percentage of defect fill in the defects subjected to the higher compression level (P < 0.05). Increasing the compressive force applied to bone graft particulate used to fill small defects created in rabbit calvaria appears to be beneficial. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. [The effects of a benzopyrone derivative in experimental brain edema due to cold in the rabbit].

    PubMed

    Góngora Castillo, C; Gómez de Segura, I A; López Bravo, A; de Miguel del Campo, E

    1993-01-01

    On this study, parenchymal changes during a cerebral edema caused by thermic injury (cool) on the rabbit, are analyzed. The work was based on the ultrastructural findings obtained by transmission electronic microscopy and on the effects produced by a benzopironic derived (F-117 Hydrosmina). The injury was produced with solid CO2, previous a craniectomy, on the dura mater of the left hemisphere. Forty rabbits were included into the study, the animals were distributed into five groups (n = 8): a control group and 4 treatment groups. One of the groups received treatment without previous cerebral injury. The group of rabbits with doses of 50 mg/Kg of weight showed focal and diffuse areas of edema alternating with less damaged areas, the edema was evident on the white substance. This group also showed a dissociation of the myelinic fibers and an intracytoplasmatic tumefaction into the glial cells. These findings contrast with the histopathological findings obtained from the rabbits (V), the extracellular edema was poor, the myelinic fiber disorganization was minimal with no vacuolar degeneration and no structural mitochondrial changes had been showed. The discontinuance of the hematoencephalic barrier caused by the cool could be a possible mechanism that causes the opening of the endothelial unions from the capillary vessels, changing their membranes and resulting in a free penetration of the molecule into the cerebral parenchyma.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Antibodies to calmodulin during experimental Trypanosoma brucei rhodesiense infections in rabbits.

    PubMed Central

    Ruben, L; Patton, C L

    1985-01-01

    Calmodulin is an intracellular Ca2+ receptor protein which regulates a wide variety of enzymatic processes in eukaryotic cells examined in detail. Native calmodulin is not antigenic in rabbits because of its small size, high degree of amino acid sequence conservation and hydrophobicity. African trypanosomes contain a novel calmodulin which is structurally distinct from bovine brain and Tetrahymena calmodulins. In the present study, we examine the antibody response towards these calmodulins during chronic Trypanosoma brucei rhodesiense infections. Injection of purified trypanosome calmodulin into rabbits stimulates the production of specific IgG antibodies which recognize trypanosome, but not bovine brain or Tetrahymena calmodulins. By contrast, during chronic T. brucei infections in rabbits, antibodies (IgG + IgM + IgA) that recognize trypanosome, Tetrahymena and mammalian calmodulins arise. When only IgG antibodies are evaluated from infection sera, the major response is against mammalian and Tetrahymena calmodulins. Significantly fewer IgG antibodies are measured in the infection sera which recognize trypanosome calmodulin, while the non-specific control protein, chicken ovalbumin, is not recognized. Peak IgG antibody responses against calmodulin occur between Days 30-34 post-infection. Competition assays indicate that Tetrahymena and mammalian calmodulins are recognized at identical epitopes which are distinct from epitopes on trypanosome calmodulin. We conclude that, in the context of chronic T. brucei infections in rabbits, antibodies arise which are able to recognize mammalian host calmodulin. Images Figure 1 PMID:2414212

  13. Combination therapy with terbinafine and amphotericin B in a rabbit model of experimental invasive aspergillosis.

    PubMed

    Kirkpatrick, William R; Vallor, Ana C; McAtee, Robert K; Ryder, Neil S; Fothergill, Annette W; Rinaldi, Michael G; Patterson, Thomas F

    2005-11-01

    Antagonistic effects of combination therapy using amphotericin B (AmB) with agents which block ergosterol synthesis are a concern. Terbinafine was evaluated with AmB to assess antagonism or synergy in a rabbit model of invasive aspergillosis. Terbinafine had relatively little activity but did not demonstrate antagonism against AmB in our model.

  14. Efficacy of ceftaroline fosamil against penicillin-sensitive and -resistant streptococcus pneumoniae in an experimental rabbit meningitis model.

    PubMed

    Cottagnoud, P; Cottagnoud, M; Acosta, F; Stucki, A

    2013-10-01

    Ceftaroline is a new cephalosporin with bactericidal activity against resistant Gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae, as well as common Gram-negative organisms. This study tested the prodrug, ceftaroline fosamil, against a penicillin-sensitive and a penicillin-resistant strain of S. pneumoniae in an experimental rabbit meningitis model. The penetration of ceftaroline into inflamed meninges was approximately 14%. Ceftaroline fosamil was slightly superior to ceftriaxone against the penicillin-sensitive strain and significantly superior to the combination of ceftriaxone and vancomycin against the penicillin-resistant strain.

  15. Laser-induced hyperthemia in the treatment of ocular tumors: experimental evaluation of temperature rise in rabbits' eyes

    NASA Astrophysics Data System (ADS)

    Svaasand, Lars O.; Morinelli, Elisa; Gomer, Charles J.

    1990-08-01

    Experimental results for the optical properties of ocular tumors in the red to near infrared region from 600-900 nm and at the near infrared wavelength of 1064 nm are presented. The tumor models have been human retinoblastoma heterotransplanted in athyinic mice and B16 melanotic melanoma in athymic mice. The steady state retinal and tumor temperature rise during 1064 nm laser irradiation have been examined in vivo in normal albino and pigmented rabbits eye and in Greene''s melanoma inoculated in the retinachoroidal layers. 2.

  16. Experimental transmission of rabbit haemorrhagic disease virus (RHDV) from rabbit to wild mice (Mus spretus and Apodemus sylvaticus) under laboratory conditions.

    PubMed

    Rocha, Gregorio; Alda, Fernando; Pagés, Albert; Merchán, Tomás

    2017-01-01

    Rabbit haemorrhagic disease (RHD) is a highly lethal and contagious viral disease that produces haemorrhagic lesions in liver and lungs of domestic and wild rabbits (Oryctolagus cuniculus). This study investigates the transmission of RHDV from infected rabbits to mice, based on the detection of viral RNA. Sixteen wild mice (Mus spretus, n=12 and Apodemus sylvaticus, n=4) were put in contact with nine rabbits inoculated with RHDV. No mice died following exposure to RHDV-infected rabbits or developed macroscopic haemorrhagic lesions. On the fourth day of contact, RHDV was detected by RT-PCR in the faeces of three of the four mice killed and in the livers of two of them. Three days after contact period with the inoculated rabbits (7th day of the experiment), RHDV was detected by RT-PCR in 100% (n=4) of the faeces and 50% (n=2) of the livers of euthanized animals. Ten days after contact period (14th day of the experiment), RHDV was not detected in the faeces or liver from any of the mice euthanized. However, 64days after contact period, RHDV was detected in the faeces of one mouse (1 of 4). We demonstrate cross-species transmission of RHDV-RNA from rabbit to rodent and the capability of RHDV-RNA to persist in mice for at least 10days after contact, and potentially up to two months, although viral replication within the rodent and/or infectivity was not evaluated in the present study.

  17. [Rabbit facial nerve damager after Nd: YAG laser irradiation: an experimental study

    PubMed

    Yu, Y C; Zhang, Z Y; Zhou, G Y; Zhu, H G

    1999-12-01

    OBJECTIVE:To investigate the change effects of rabbit facial nerve after Nd:YAG laser irradiation.METHODS: According to therapeutic laser energy density,the facial nerves of 28 rabbits were irradiated by Nd:YAG laser with 5 different laser dosages.RESULTS: The facial nerves were functionally intact with mild degeneration histologically at three weeks postoperatively,when the energy density of Nd: YAG laserlaser lower than 70J/cm(2).In the group with energy density of 140J/cm(2),facial nerve density functionally impaired with moderate degeneration which rehabilitated within six weeks. While the laser power increaseed to more than 240J/cm(2),irreversible nerve damages happened.CONCLUSION: laser thermal effect is the main cause of nerve damage,there is a positive correlation between laser dosage and nerve impairment.

  18. Macrophage-targeted photodynamic detection of vulnerable atherosclerotic plaque

    NASA Astrophysics Data System (ADS)

    Hamblin, Michael R.; Tawakol, Ahmed; Castano, Ana P.; Gad, Faten; Zahra, Touqir; Ahmadi, Atosa; Stern, Jeremy; Ortel, Bernhard; Chirico, Stephanie; Shirazi, Azadeh; Syed, Sakeena; Muller, James E.

    2003-06-01

    Rupture of a vulnerable atherosclerotic plaque (VP) leading to coronary thrombosis is the chief cause of sudden cardiac death. VPs are angiographically insignificant lesions, which are excessively inflamed and characterized by dense macrophage infiltration, large necrotic lipid cores, thin fibrous caps, and paucity of smooth muscle cells. We have recently shown that chlorin(e6) conjugated with maleylated albumin can target macrophages with high selectivity via the scavenger receptor. We report the potential of this macrophage-targeted fluorescent probe to localize in VPs in a rabbit model of atherosclerosis, and allow detection and/or diagnosis by fluorescence spectroscopy or imaging. Atherosclerotic lesions were induced in New Zealand White rabbit aortas by balloon injury followed by administration of a high-fat diet. 24-hours after IV injection of the conjugate into atherosclerotic or normal rabbits, the animals were sacrificed, and aortas were removed, dissected and examined for fluorescence localization in plaques by fiber-based spectrofluorimetry and confocal microscopy. Dye uptake within the aortas was also quantified by fluorescence extraction of samples from aorta segments. Biodistribution of the dye was studied in many organs of the rabbits. Surface spectrofluorimetry after conjugate injection was able to distinguish between plaque and adjacent aorta, between atherosclerotic and normal aorta, and balloon-injured and normal iliac arteries with high significance. Discrete areas of high fluorescence (up to 20 times control were detected in the balloon-injured segments, presumably corresponding to macrophage-rich plaques. Confocal microscopy showed red ce6 fluorescence localized in plaques that showed abundant foam cells and macrophages by histology. Extraction data on aortic tissue corroborated the selectivity of the conjugate for plaques. These data support the strategy of employing macrophage-targeted fluorescent dyes to detect VP by intravascular

  19. Cartilage repair of experimentally 11 induced osteochondral defects in New Zealand White rabbits.

    PubMed

    Aulin, C; Jensen-Waern, M; Ekman, S; Hägglund, M; Engstrand, T; Hilborn, J; Hedenqvist, P

    2013-01-01

    Articular cartilage has a limited capacity for self-repair in adult humans, and methods used to stimulate regeneration often result in re-growth of fibrous cartilage, which has lower durability. No current treatment option can provide complete repair. The possibility of growth factor delivery into the joint for cartilage regeneration after injury would be an attractive treatment option. A full thickness osteochondral defect of 4 mm in diameter and 2 mm deep was created by mechanical drilling in the medial femoral condyle in 20 female adult New Zealand White rabbits. In an attempt to improve regeneration a hyaluronic hydrogel system, with or without bone morphogenetic protein-2 (BMP-2) was delivered intraarticularly. The contralateral joint defect was treated with saline as control. Throughout the study, rabbits were clinically examined and after 12 (n = 6) or 24 (n = 9) weeks, the rabbits were euthanized and the joints evaluated by histology. The defects healed with fibrocartilage like tissue, and the filling of the defects ranged from less than 25% to complete. The healing of the defects varied both inter- and intra-group wise. Treatment with hyaluronan gel with or without BMP-2 had no effect on cartilage regeneration compared with controls. Instead, severe ectopic bone formation was found in seven joints treated with BMP-2. In conclusion, the present study shows that neither treatment with hyaluronic gel alone, nor in combination with BMP-2, improves the healing of an induced cartilage defect in rabbits. It further shows that BMP-2 can induce ectopic bone formation, which severely affects the functionality of the joint.

  20. Eimeria stiedae: experimental infection in rabbits and the effect of treatment with toltrazuril and ivermectin.

    PubMed

    Cam, Yücel; Atasever, Ayhan; Eraslan, Gökhan; Kibar, Murat; Atalay, Oznur; Beyaz, Latife; Inci, Abdullah; Liman, Bilal Cem

    2008-05-01

    The aim of this study was to investigate the clinical, haematological, biochemical, lipid peroxidation, ultrasonographic and pathologic findings in hepatic coccidiosis induced by Eimeria stiedae in rabbits, and also to compare the treatment effects of both toltrazuril and ivermectin separately and in combination. In this study, 56 rabbits were divided into eight groups. The first group was designated as healthy control group. Rabbits were infected with 40.000 sporulated oocysts of E. stiedae. Groups 2, 3, 4, 5, 6, 7 and 8 were allocated as the infected control group, infected+toltrazuril-treated group, infected+ivermectin-treated group, infected+toltrazuril+ivermectin-treated group, non-infected+toltrazuril-treated group, non-infected+ivermectin-treated group, non-infected+toltrazuril+ivermectin-treated group, respectively. Haematocrit, Haemoglobin and MCV values as well as percentage of lymphocyte decreased in Groups 2 and 4 whereas leucocyte counts and percentage of granulocyte leucocyte increased. Serum GGT, ALT and AST activities increased but albumin value decreased. Plasma MDA concentrations increased whereas erythrocyte CAT, GSH-Px, and SOD activities decreased. Mean oocyst numbers in per gram faeces (epg values) increased in both groups during the study. Ultrasonographic examination revealed that the liver was enlarged and had hyperechogenic parenchyma. Bile ducts were dilated and hyperechogenic and the gall bladder was dilated. The livers of these animals were enlarged and typical macroscopic and microscopic findings of coccidiosis were present. Treatment with toltrazuril and toltrazuril+ivermectin combination were highly effective in reducing faecal oocyst output in infected rabbits. Haematological, biochemical and lipid peroxidation parameters and, ultrasonographic findings of the liver were close to control values for Groups 3 and 5. Necropsy of these animals showed no visible lesions related to hepatic coccidiosis although a few oocysts were detected

  1. Capsular bag opacification after experimental implantation of a new accommodating intraocular lens in rabbit eyes.

    PubMed

    Werner, Liliana; Pandey, Suresh K; Izak, Andrea M; Vargas, Luis G; Trivedi, Rupal H; Apple, David J; Mamalis, Nick

    2004-05-01

    To evaluate the development of capsular bag opacification in rabbit eyes after implantation of an intraocular lens (IOL) designed to minimize contact between the anterior capsule and the IOL and ensure expansion of the capsular bag. David J. Apple, MD Laboratories for Ophthalmic Devices Research, John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, USA. Ten New Zealand white rabbits had a study IOL (new accommodating silicone IOL [Synchrony, Visiogen, Inc.]) implanted in 1 eye and a control IOL (1-piece plate silicone IOL with large fixation holes) implanted in the other eye. Intraocular lens position, anterior capsule opacification (ACO), and posterior capsule opacification (PCO) were qualitatively assessed using slitlamp retroillumination photographs of the dilated eyes. Anterior capsule opacification and PCO were graded on a 0 to 4 scale after the eyes were enucleated (Miyake-Apple posterior and anterior views after excision of the cornea and iris). The eyes were also evaluated histopathologically. The rate of ACO and PCO was significantly higher in the control group. Fibrosis and ACO were almost absent in the study group; the control group exhibited extensive capsulorhexis contraction, including capsulorhexis occlusion. Postoperative IOL dislocation into the anterior chamber and pupillary block syndrome were observed in some eyes in the study group. The special design features associated with the study IOL appeared to help prevent PCO. Complications in the study group were probably caused by the increased posterior vitreous pressure in rabbit eyes compared to human eyes and the relatively large size of the study IOL relative to the anterior segment of rabbit eyes.

  2. Experimental study of sutureless vascular anastomosis with use of glued prosthesis in rabbits.

    PubMed

    Vokrri, Lulzim; Qavdarbasha, Arsim; Rudari, Hajriz; Ahmetaj, Halil; Manxhuka-Kërliu, Suzana; Hyseni, Nexhmi; Porcu, Paolo; Cinquin, Philippe; Sessa, Carmine

    2015-01-01

    The objective of this study is to explore the feasibility and efficacy of a new technique for sutureless vascular anastomosis, using glued prosthesis, as a sole anastomosis fixation method in rabbits. Ten rabbits were randomly selected to conduct the experiment. Five rabbits underwent direct anastomosis of infrarenal abdominal aorta, with glued prosthesis. In five other rabbits, reconstruction was done by sutured anastomosis. All animals were immediately examined by echo-Doppler for patency of anastomosis. The burst pressure of the glued anastomosis was measured and compared with that of a sutured artery. The animals were euthanized, and tissue samples were taken for histological examination immediately after the experiment. Compared to conventional anastomoses, sutureless vascular anastomoses required shorter time of creation and significantly reduced blood loss (P<5%). There was no significant difference on the average blood flow through the anastomosis between two groups at the end of surgery. All anastomoses with glued prosthesis, examined by echo-Doppler, were patent at the anastomotic site, except one, which was stenosed immediately after surgery. In the control group, except one with stenosis, all conventional anastomoses were patent. Mean burst pressure at the anastomotic site for sutureless anastomoses was lower than in control group. Macroscopically, the BioGlue did not demonstrate any adhesion to the surrounding tissue as it was covered by the vascular prosthesis. Histological examination showed low-grade inflammatory reaction in glued anastomoses versus no inflammatory reaction at the sutured anastomoses. This technique may provide a feasible and successful alternative in vascular surgery. However, further long-term studies are necessary to elucidate the break pressure and degree of inflammation at the anastomotic site.

  3. Neurologic Evaluation of Acute Lacrimomimetic Effect of Cyclosporine in an Experimental Rabbit Dry Eye Model

    PubMed Central

    Toshida, Hiroshi; Nguyen, Doan H.; Beuerman, Roger W.; Murakami, Akira

    2010-01-01

    PURPOSE To evaluate neurologically acute lacrimation caused by cyclosporine (CsA) eyedrops in rabbit. METHODS Normal adult male New Zealand White rabbits and those that underwent parasympathectomy each received a single instillation of 0.1% CsA or vehicle eyedrops. Schirmer tear test (STT) results, flow rate of lacrimal gland (LG) fluid from the excretory lacrimal duct of the main LG, and blink rate (over a 3-minute period) were measured before and after instillation of CsA or vehicle. Light microscopy was performed to examine the main LG in vitro. Protein release from LG fragments was assessed after incubation with CsA for 30 minutes. RESULTS In normal rabbits, the STT value and the flow rate of LG fluid were significantly increased after treatment with CsA compared with vehicle (P < 0.05). In contrast, no changes were found in denervated eyes. The blink rate of CsA-treated eyes was significantly higher than that of vehicle- treated eyes in normal rabbits (P < 0.005), whereas that of denervated eyes decreased significantly after CsA instillation compared with before administration (P < 0.005). Light microscopy showed that the cytoplasm of acinar cells was packed with secretory granules in denervated LG tissue 7 days after parasympathectomy. The same finding was observed 3 hours after CsA instillation. CsA had no stimulatory effect on protein release by acinar cells in LG fragments at all concentrations tested. CONCLUSIONS These results suggest that CsA has no direct effect on tear fluid secretion from the LG in an acute model. Instead, CsA increases reflex tear flow. PMID:19218606

  4. Experimental study of sutureless vascular anastomosis with use of glued prosthesis in rabbits

    PubMed Central

    Vokrri, Lulzim; Qavdarbasha, Arsim; Rudari, Hajriz; Ahmetaj, Halil; Manxhuka-Kërliu, Suzana; Hyseni, Nexhmi; Porcu, Paolo; Cinquin, Philippe; Sessa, Carmine

    2015-01-01

    Objective The objective of this study is to explore the feasibility and efficacy of a new technique for sutureless vascular anastomosis, using glued prosthesis, as a sole anastomosis fixation method in rabbits. Methods Ten rabbits were randomly selected to conduct the experiment. Five rabbits underwent direct anastomosis of infrarenal abdominal aorta, with glued prosthesis. In five other rabbits, reconstruction was done by sutured anastomosis. All animals were immediately examined by echo-Doppler for patency of anastomosis. The burst pressure of the glued anastomosis was measured and compared with that of a sutured artery. The animals were euthanized, and tissue samples were taken for histological examination immediately after the experiment. Results Compared to conventional anastomoses, sutureless vascular anastomoses required shorter time of creation and significantly reduced blood loss (P<5%). There was no significant difference on the average blood flow through the anastomosis between two groups at the end of surgery. All anastomoses with glued prosthesis, examined by echo-Doppler, were patent at the anastomotic site, except one, which was stenosed immediately after surgery. In the control group, except one with stenosis, all conventional anastomoses were patent. Mean burst pressure at the anastomotic site for sutureless anastomoses was lower than in control group. Macroscopically, the BioGlue did not demonstrate any adhesion to the surrounding tissue as it was covered by the vascular prosthesis. Histological examination showed low-grade inflammatory reaction in glued anastomoses versus no inflammatory reaction at the sutured anastomoses. Conclusion This technique may provide a feasible and successful alternative in vascular surgery. However, further long-term studies are necessary to elucidate the break pressure and degree of inflammation at the anastomotic site. PMID:25848302

  5. Experimental observation of human bone marrow mesenchymal stem cell transplantation into rabbit intervertebral discs

    PubMed Central

    Tao, Hao; Lin, Yazhou; Zhang, Guoqing; Gu, Rui; Chen, Bohua

    2016-01-01

    Allogeneic bone marrow mesenchymal stem cell (BMSC) transplantation has been investigated worldwide. However, few reports have addressed the survival status of human BMSCs in the intervertebral discs (IVDs) in vivo following transplantation. The current study aimed to observe the survival status of human BMSCs in rabbit IVDs. The IVDs of 15 New Zealand white rabbits were divided into three groups: Punctured blank control group (L1-2); punctured physiological saline control group (L2-3); and punctured human BMSCs transfected with green fluorescent protein (GFP) group (L3-4, L4-5 and L5-6). One, 2, 4, 6 and 8 weeks after transplantation the IVDs were removed and a fluorescence microscope was used to observe the density of GFP-positive human BMSCs. The results indicated that in the sections of specimens removed at 1, 2, 4, 6 and 8 weeks post-transplantation, no GFP-positive cells were observed in the control groups, whereas GFP-positive cells were apparent in the nucleus pulposus at all periods in the GFP-labeled human BMSCs group, and the cell density at 6 and 8 weeks was significantly less than that at 1, 2 and 4 weeks post-transplantation (P<0.001). Thus, it was identified that human BMSCs were able to survive in the rabbit IVDs for 8 weeks. PMID:27588177

  6. Apoptosis and electroretinogram after intravitreal injection of methotrexate in an experimental rabbit model.

    PubMed

    Aly, Eman; Ebrahim, Amal

    2016-04-01

    The aim of this study was to explore the changes in electroretinogram of rabbit retina and apoptosis in methotrexate-induced toxicity. Rabbits were divided into 5 groups. Group I served as control in which saline solutions was injected intravitreally. Methotrexate (800 μg, 1.76 μmol) was injected into the vitreous of both eyes of rabbits groups II, III, IV and V by an insulin injector with a 26 gauge needle under general anesthesia. Retinal function was assessed by electroretinogram (ERG) after 2, 4, 10 days and one month then animals were decapitated. The eyes were enucleated and processed for DNA fragmentation studies by gel electrophoresis to retinae and measurement of caspase-3 activities. The results indicated a significant reduction (p ˂ 0.05) in a- and b-wave, a time-dependent appearance of the typical ladder pattern of internucleosomal fragmentation, a characteristic of apoptosis and increase of relative caspase-3 activity after methotrexate intravitreal injection. Methotrexate lead to apoptosis, increase of caspase-3 and affect retinal function.

  7. Effects of postoperative immobilization on the reconstructed anterior cruciate ligament. An experimental study in rabbits.

    PubMed

    Muneta, T; Yamamoto, H; Takakuda, K; Sakai, H; Furuya, K

    1993-01-01

    To investigate the effects of postoperative immobilization and limited motion on reconstructed anterior cruciate ligaments, 28 rabbits received an anterior cruciate ligament reconstruction using autogenous Achilles tendon and were then divided into three groups: fully immobilized, 4 weeks immobilized, and limited motion. Two rabbits from each group were evaluated macroscopically, histologically and microangiographically at 4-week intervals until 12 weeks postoperatively. An additional six rabbits in the 4 weeks immobilized and limited motion groups were studied biomechanically at 12 weeks postoperatively. Macroscopically, both immobilized groups showed more proliferation of the infrapatellar fat pad, which was adherent to the reconstructed anterior cruciate ligament. Histology revealed more rapid regeneration of reconstructed anterior cruciate ligaments in the limited motion group, with no findings of necrosis in the mid-substance. Microangiography indicated faster normalization of vascularity in the limited motion group. The biomechanical study showed no significant difference in laxity between the 4 weeks immobilized and limited motion groups. The graft stiffness and maximum load to failure were greater for the limited motion group, although the increase was not statistically significant. The histologic and microangiographic results from the limited number of animals in this study support limited postoperative motion in the anterior cruciate ligament reconstructed knee. However, there were no differences in terms of the biomechanical parameters at 12 weeks postoperatively between the immobilized and limited motion treatment modes.

  8. Effects of cortical bone perforation on periosteal distraction: an experimental study in the rabbit mandible.

    PubMed

    Oda, Tomoo; Kinoshita, Kazuhiko; Ueda, Minoru

    2009-07-01

    To investigate tissue reactions using periosteal distraction with decorticating holes in a rabbit model. Twenty-five Japanese white rabbits weighing 3.2 to 3.7 kg were used. The periosteum was carefully detached, and the buccal cortical bone was porously perforated by drilling in the decortication group. Titanium mesh was placed between the periosteum and the cortical bone, with or without holes. A distraction screw was placed rigidly under the center of the mesh. After a 7-day latency period, the periosteum was distracted 0.5 mm per day for 8 consecutive days. Rabbits were sacrificed after consolidation periods of 4 and 8 weeks. Cross-sectional radiographs were evaluated with densitometry. Specimens were fixed, decalcified, and stained with hematoxylin and eosin. At 8 weeks after periosteal distraction, the area of new bone formation averaged 25.7 +/- 5.1 mm2 and 12.9 +/- 3.2 mm2 (mean +/- SD) with and without decortication, respectively. In this study, periosteal distraction showed better bone regeneration on the lateral aspect of mandibles with rather than without decorticating holes. Periosteal distraction with decorticating holes can be effective in augmenting atrophic bone.

  9. Evaluation of bee venom and hyaluronic acid in the intra-articular treatment of osteoarthritis in an experimental rabbit model.

    PubMed

    Ozlem Nisbet, H; Ozak, Ahmet; Yardimci, Cenk; Nisbet, Cevat; Yarim, Murat; Bayrak, I Koray; Sirin, Y Sinan

    2012-08-01

    The aim of this study was to investigate bee venom and hyaluronic acid in the intra-articular treatment of osteoarthritis in an experimental rabbit model. Forty-five rabbits were used and they were randomly divided into three groups (BVI, BVII, and HA) and each group was divided to two subgroups to evaluate the radiologic, magnetic resonance imaging, histopathologic, and biochemical evaluation in post treatment second week (a) and twelfth week (b). Radiologically, a significant difference was observed in the HA group (P<0.05). The MRI evaluation of at any time in group BVI(b) was found to be different. No significant differences were seen between the groups, biochemically. Histopathologically, cellularity, and orthochromasia was evident with Safranin-O in the BVI(b) and BVII(a); adhesions were seen in the BVII(a) group and clustering of chondrocyte in the HA(b) group were found to be different. Consequently, intra-articular application of HA and BV for experimental model of osteoarthritis has no significant influence upon recovery after therapy. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Effects of local administration of growth hormone in peri-implant bone: an experimental study with implants in rabbit tibiae.

    PubMed

    Tresguerres, Isabel F; Blanco, Luis; Clemente, Celia; Tresguerres, Jesús A F

    2003-01-01

    The objective of this study was to evaluate the qualitative and quantitative differences that could appear in newly formed peri-implant bone around Screw-Vent implants placed in rabbit tibiae when treated with local administration of growth hormone (GH). Eight New Zealand rabbits were randomly divided into 2 groups: the experimental group, which received 4 IU of GH in the form of lyophilized powder added to the ostectomy site before implant placement, and the control group, which did not receive GH before implant placement. Animals were sacrificed 2 weeks later, and histologic sections were obtained for histomorphometry and observation under light microscopy. The sections in the GH-treated group presented enhanced growth of new trabeculae from the periosteal tissue, and the bone-to-implant contact in the experimental group was significantly greater (P < .05). Local administration of GH stimulated a more dramatic effect than that seen previously with systemic GH administration, prompting growth from both the periosteum and endosteum. Local administration of GH at the time of implant placement could enhance peri-implant bone reaction.

  11. [Experimental study on vascular bundle implantation combined with cellular transplantation in treating rabbit femoral head necrosis].

    PubMed

    Chen, Shuang-Tao; Zhang, Wei-Ping; Liu, Chang-An; Wang, Jun-Jiang; Song, Heng-Yi; Chai, Zhi-wen

    2013-03-01

    To discuss the feasibility of vascular bundle implantation combined with allogeneic bone marrow stromal cells (BMSCs) transplantation in treating rabbit femoral head osteonecrosis and bone defect, in order to explore a new method for the treatment of femoral head necrosis. Thirty-six New Zealand rabbits were randomly divided into three groups,with 12 rabbits in each group. Bilateral femoral heads of the rabbits were studied in the experiment. The models were made by liquid nitrogen frozen, and the femoral heads were drilled to cause bone defect. Group A was the control group,group B was stem cells transplantaion group of allograft marrow stromal,and group C was stem cells transplantation group of allograft marrow stromal combined with vascular bundle implantation. Three rabbits of each group were sacrificed respectively at 2, 4, 8, 12 weeks after operation. All specimens of the femoral heads were sliced for HE staining. Furthermore ,vascular density and the percentage of new bone trabecula of femoral head coronary section in defect area were measured and analyzed statistically. In group C,new bone trabecula and original micrangium formed at the 2nd week after operation; new bone trabecula was lamellar and interlaced with abundant micrangium at the 8th week;at the 12th week,the broadened,coarsened bone trabecula lined up regularly,and the mature bone trabecula and new marrow were visible. At the 2nd week after operation,there was no statistical significance in the percentage of new bone trabecula of femoral head coronary section in defect area between group B and C. While at 4, 8, 12 week after operation, vascular density and the percentage of new bone trabecula of femoral head coronary section in defect area of group C was higher than that of group B. Allogeneic bone marrow stromal cells cultured in vivo can form new bone trabecula, and can be applied to allotransplant. Vascular bundle implanted into the bone defect area of femoral head necrosis could improve blood

  12. [Impacts of early metoprolol intervention on connexin 43 and phosphorylated connexin 43 expression in rabbits with experimental myocardial infarction].

    PubMed

    Zhou, M; Lu, Q; Jiang, J Q; Chen, Z N; Gong, Z G; Li, Z G; Fu, W W; Ding, S F

    2017-04-24

    P<0.05). (3) Immunofluorescence analyses showed that Cx43 was mainly localized in the intercalated disk, which was perpendicular to the cell long axis with linear arrangement, and less lateral distribution in sham group, early treatment group and routine treatment group, which was significantly different as the case in the myocardial infarction group. The expression of p-Cx43 in myocardial infarction group was less than in sham group, which was significantly upregulated in in early treatment group and routine treatment group when compared with myocardial infarction group, and expression of p-Cx43 was significantly higher in early treatment group than in routine treatment group. (4)The p-Cx43/Cx43 ratio of protein was significantly lower in myocardial infarction group than in sham group (0.165±0.011 vs. 0.363±0.046, P<0.05), and significantly higher in early treatment group (0.720±0.063) and routine treatment group (0.364±0.030) than in myocardial infarction group (both P<0.05), and this ratio was significantly higher in early treatment group than in routine treatment group (P<0.05). Conclusion: Metoprolol treatment, especially the early metoprolol treatment (within 24 hours after LAD ligation), could significantly improve VFT by ameliorating the distribution and dephosphorylation of myocardial Cx43 in rabbits with experimental myocardial infarction.

  13. Atherosclerosis induced by chronic inhibition of the synthesis of nitric oxide in moderately hypercholesterolaemic rabbits is suppressed by pitavastatin

    PubMed Central

    Kitahara, Masaki; Kanaki, Tatsuro; Ishii, Itsuko; Saito, Yasushi

    2010-01-01

    Background and purpose: It is not clear if the new 3-hydroxyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor pitavastatin prevents atherogenesis by a direct effect. Statins have a cholesterol-lowering effect, so an accessible animal model of atherosclerosis showing only moderate hypercholesterolaemia as in humans, is needed. The effects of pitavastatin were evaluated on atherosclerotic lesions accumulating foam cells derived from macrophages, produced in rabbits with moderate hypercholesterolaemia by chronic inhibition of nitric oxide synthase (NOS). Experimental approach: White New Zealand rabbits were fed a 0.2% cholesterol diet with the NOS inhibitor Nω-nitro-L-arginine methyl ester (L-NAME) in the same diet. Pitavastatin (0.1 and 0.3 mg·kg−1) was given orally once a day for 8 weeks. The aortic arch and thoracic aorta were analysed by histochemistry and atherosclerotic lesions were quantified. The effect of pitavastatin on adhesion of THP-1 cells to endothelial cells, and cholesterol content in RAW264.7 cells incubated with oxidized or acetylated LDL were also investigated. Key results: Atherosclerotic lesions containing foam cells were induced in a model of atherosclerosis in rabbits with moderate hypercholesterolaemia by chronic inhibition of NOS. The area of atherosclerotic lesions was diminished by pitavastatin administration. The adhesion of THP-1 cells and cholesteryl ester content in RAW macrophages were decreased by pitavastatin treatment. Conclusion: Atherosclerosis induced by chronic inhibition of NOS in moderately hypercholesterolaemic rabbits was suppressed by pitavastatin via inhibition of macrophage accumulation and macrophage foam cell formation. PMID:20233214

  14. CD44 targeting magnetic glyconanoparticles for atherosclerotic plaque imaging.

    PubMed

    El-Dakdouki, Mohammad H; El-Boubbou, Kheireddine; Kamat, Medha; Huang, Ruiping; Abela, George S; Kiupel, Matti; Zhu, David C; Huang, Xuefei

    2014-06-01

    The cell surface adhesion molecule CD44 plays important roles in the initiation and development of atherosclerotic plaques. We aim to develop nanoparticles that can selectively target CD44 for the non-invasive detection of atherosclerotic plaques by magnetic resonance imaging. Magnetic glyconanoparticles with hyaluronan immobilized on the surface have been prepared. The binding of these nanoparticles with CD44 was evaluated in vitro by enzyme linked immunosorbent assay, flow cytometry and confocal microscopy. In vivo magnetic resonance imaging of plaques was performed on an atherosclerotic rabbit model. The magnetic glyconanoparticles can selectively bind CD44. In T2* weighted magnetic resonance images acquired in vivo, significant contrast changes in aorta walls were observed with a very low dose of the magnetic nanoparticles, allowing the detection of atherosclerotic plaques. Furthermore, imaging could be performed without significant delay after probe administration. The selectivity of hyaluronan nanoparticles in plaque imaging was established by several control experiments. Magnetic nanoparticles bearing surface hyaluronan enabled the imaging of atherosclerotic plaques in vivo by magnetic resonance imaging. The low dose of nanoparticles required, the possibility to image without much delay and the high biocompatibility are the advantages of these nanoparticles as contrast agents for plaque imaging.

  15. CD44 Targeting Magnetic Glyconanoparticles for Atherosclerotic Plaque Imaging

    PubMed Central

    El-Dakdouki, Mohammad H.; El-Boubbou, Kheireddine; Kamat, Medha; Huang, Ruiping; Abela, George S.; Kiupel, Matti; Zhu, David C.; Huang, Xuefei

    2013-01-01

    Purpose The cell surface adhesion molecule CD44 plays important roles in the initiation and development of atherosclerotic plaques. We aim to develop nanoparticles that can selectively target CD44 for the non-invasive detection of atherosclerotic plaques by magnetic resonance imaging. Methods Magnetic glyco-nanoparticles with hyaluronan immobilized on the surface have been prepared. The binding of these nanoparticles with CD44 in vitro was evaluated by enzyme linked immunosorbent assay, flow cytometry and confocal microscopy. In vivo magnetic resonance imaging of plaques was performed on an atherosclerotic rabbit model. Results The magnetic glyconanoparticles can selectively bind CD44. In T2* weighted magnetic resonance images acquired in vivo, significant contrast changes in aorta walls were observed with a very low dose of the magnetic nanoparticles, allowing the detection of atherosclerotic plaques. Furthermore, imaging could be performed without significant delay after probe administration. The selectivity of hyaluronan nanoparticles in plaque imaging was established by several control experiments. Conclusions Magnetic nanoparticles bearing surface hyaluronan enabled the imaging of atherosclerotic plaques in vivo by magnetic resonance imaging. The low dose of nanoparticles required, the possibility to image without much delay and the high biocompatibility are the advantages of these nanoparticles as contrast agents for plaque imaging. PMID:23568520

  16. Assessment of tissue viability after frostbite injury by technetium-99m-sestamibi scintigraphy in an experimental rabbit model.

    PubMed

    Sarikaya, I; Aygit, A C; Candan, L; Sarikaya, A; Türkyilmaz, M; Berkarda, S

    2000-01-01

    Frostbite causes injury to the tissue by direct ice-crystal formation at the cellular level with cellular dehydration and microvascular occlusion. Muscle that initially appears viable on reperfusion may subsequently become necrotic because of microcirculatory collapse. Since muscle is a sensitive tissue in frostbite injury, we used technetium-99m-sestamibi limb scintigraphy to assess tissue viability in an experimental rabbit model. Twelve rabbits were used for this investigation. The right hind limb of the rabbits was immersed to the ankle joint in a container filled with 90% ethanol at -25 degrees C for 10 min. Frostbitten limbs were allowed to thaw in air at room temperature. Imaging and pathological examination of the affected limbs were performed 2 h, 24 h, 48 h and 72 h after freezing. In 2-h images, initial hypoperfusion was seen that corresponded to circulatory collapse. In 24-h images, there was hyperperfusion (so-called period of temporary reperfusion), corresponding to circulatory restoration. In 48-h images, a second hypoperfusion corresponded to viable but ischaemic tissue. In 72-h images, there was non-perfusion of the limb that correlated with the pathologically determined diagnosis of necrosis. All scintigraphic patterns correlated with pathological findings. We suggest that these scintigraphic patterns in soft tissue may be helpful in distinguishing between frank infarction and reversible ischemia and therefore may be useful in selecting early therapeutic or surgical interventions to salvage bone and soft tissue. Further studies are needed to show the usefulness of 99mTc sestamibi scintigraphy in clinical frostbite cases.

  17. Experimental erbium: YAG laser photoablation of trabecular meshwork in rabbits: an in-vivo study.

    PubMed

    Dietlein, T S; Jacobi, P C; Schröder, R; Krieglstein, G K

    1997-05-01

    Photoablative laser trabecular surgery has been proposed as an outflow-enhancing treatment for open-angle glaucoma. The aim of the study was to investigate the time course of repair response following low-thermal Erbium: YAG laser trabecular ablation. In 20 anaesthetized rabbits gonioscopically controlled ab-interno photoablation of the ligamenta pectinata and underlying trabecular meshwork (TM) was performed with a single-pulsed (200 microseconds) Erbium: YAG (2.94 microns) laser. The right eye received 12-15 single laser pulses (2 mJ) delivered through an articulated zirconium fluoride fiberoptic and a 200 microns (core diameter) quartz fiber tip, the left unoperated eye served as control. At time intervals of 30 minutes, 2, 10, 30, and 60 days after laser treatment, eyes were processed for light- and scanning electron microscopy. The applied energy density of 6-4 J cm-2 resulted in visible dissection of the ligamenta pectinata and reproducible microperforations of the TM exposing scleral tissue accompanied by blood reflux from the aqueous plexus. The initial ablation zones measured 154 +/- 36 microns in depth and 45 +/- 6 microns in width. Collateral thermal damage zones were 22 +/- 8 microns. At two days post-operative, ablation craters were still blood- and fibrin-filled. The inner surface of the craters were covered with granulocytes. No cellular infiltration of the collateral thermal damage zone was observed. At 10 days post-operative, progressive fibroblastic proliferation was observed, resulting in dense scar tissue formation with anterior synechiae, proliferating capillaries and loss of intertrabecular spaces inside the range of former laser treatment at 60 days post-operative. Trabecular microperforations were closed 60 days after laser treatment in all rabbits. IOP in treated and contralateral eyes did not significantly change its level during whole period of observation. Low-thermal infrared laser energy with minimal thermal damage to collateral

  18. Efficacy of five human melanocytic cell lines in experimental rabbit choroidal melanoma.

    PubMed

    López-Velasco, Rosario; Morilla-Grasa, Antonio; Saornil-Alvarez, María A; Ordóñez, José L; Blanco, Gonzalo; Rábano, Guillermo; Fernández, Nieves; Almaraz, Ana

    2005-02-01

    This study was undertaken to compare the ability of five uveal melanocytic cell lines to produce primary and metastatic uveal melanomas in immunosuppressed rabbits and to determine whether animal survival was improved by antibiotic administration. One hundred albino rabbit eyes, five groups of 20, were implanted in the suprachoroidal space with four melanoma cell lines (MKT-BR, OCM-1, 92-1 and SP 6.5) and one melanocytic line (UW-1). Rabbits were immunosuppressed with cyclosporin A (CsA) at a dosage of 15 mg/kg/day, decreased to 10 mg/kg/day after the fourth week. Prophylactic penicillin G, 10 to 2 x 10 IU, was administered intramuscularly at 5-day intervals. Animals were followed for 12 weeks and the ophthalmoscopic findings, weight and general well-being were recorded weekly. Autopsies were performed to study the eyes, liver and lungs under light microscopy. The mean global survival time in the groups was 43+/-4 days. Ophthalmoscopic intraocular tumours developed in 37% of the MKT-BR group, 50% of the OCM-1 group, 100% of the 92-1 group, 23% of the UW-1 group and 75% of the SP 6.5 group; histologically, tumours appeared in 36.8%, 45%, 100%, 58.8% and 100%, respectively. The 92-1 and SP 6.5 cell lines were associated with the most aggressive local behaviour. Lung metastases developed in the OCM-1 group (5%), 92-1 group (61.1%), UW-1 group (7.1%) and SP 6.5 group (42.1%), but were not present in the MKT-BR group. The 92-1 and SP 6.5 cell lines were the most efficient in local and metastatic tumour production. Prophylactic antibiotic administration did not improve animal survival.

  19. Periodic knee injections of collagen tripeptide delay cartilage degeneration in rabbit experimental osteoarthritis

    PubMed Central

    2013-01-01

    Introduction Collagen peptides have been reported to possess various biological activities for various cell types. The purposes of this study were, first, to examine the therapeutic effects of collagen tripeptide (Ctp) in rabbit osteoarthritis and, second, to explore a synergetic effect with hyaluronan (HA). Methods Osteoarthritis was induced by anterior cruciate ligament transection of the right knee in 72 Japanese white rabbits and they were divided into four groups (control, Ctp, HA and Ctp/HA). Each material was injected weekly into the knee, and knee joint samples were collected 5, 10 and 15 weeks after surgery. Macroscopic and histomorphological analyses of cartilage were conducted. Expression of type II collagen and matrix metalloproteinase-13 was also analyzed immunohistochemically. A Tukey's honestly significant difference test was used to evaluate the statistical significance of difference in the macroscopic, histological and immnohistochemical results. Results All treatment groups exhibited slightly higher resistance to the progression of osteoarthritis than the control group macroscopically 15 weeks after surgery. Histologically, intra-articular injection of Ctp significantly reduced cartilage degradation 10 weeks after surgery, and Ctp/HA significantly reduced it 5 weeks after surgery in comparison with the control. Immunohistochemically, both Ctp-treated and Ctp/HA-treated groups had significantly increased type II collagen-positive chondrocytes at the fifth week after the surgery, although the numbers of matrix metalloproteinase-13-positive chondrocytes were not affected. Conclusion Periodical injections of Ctp and Ctp/HA delayed progression of cartilage degeneration of early osteoarthritis induced by anterior cruciate ligament transection in rabbits. This effect appears to be exerted by promotion of type II collagen synthesis predominantly. PMID:23433227

  20. Drilling k-wires, what about the osteocytes? An experimental study in rabbits

    PubMed Central

    van Diest, Paul J.; Schuurman, Arnold H.; Kon, Moshe

    2007-01-01

    Introduction The function of osteocytes regarding osteonecrosis has been underestimated for a long time. Recently it has been suggested that apoptosis of osteocytes results in strong osteoclastic bone resorption. Death of osteocytes due to drilling may therefore increase the risk of K-wire loosening. The purposes of our in vivo study were to assess the minimal drill time needed to notice disappearance of osteocytes and to measure the distance of the empty osteocyte lacunae surrounding the drill tract in relation with the insertion time, directly and 4 weeks after drilling Kirschner (K-) wires into the femur and tibia of rabbits. Materials and methods Trocar tipped K-wires (70 mm length and 0.6 mm thickness) were drilled into the femur and tibia of 14 New Zealand white rabbits [mean body weight 2.81 kg (2.66–3.09 kg)]. Six rabbits were terminated following surgery (t = 0) and eight rabbits were terminated 4 weeks (t = 4) after surgery. Following termination, hematoxylin and eosin stained sections were cut from femur and tibia until the drill hole was visible. The sections were evaluated under a light microscope for the presence or absence of osteocytes in osteocyte lacunae surrounding the drill holes. Results All osteocyte lacunae were empty around the K-wires in 50 and 87% of the cases, directly and 4 weeks after the surgery, respectively. The osteocytes disappeared especially beyond a drilling time of 37 s (P = 0.011) and 27 s (P = 0.008) at t = 0 and t = 4, respectively. Furthermore, a significantly positive correlation was seen between the distances of the empty osteocyte lacunae surrounding the drill holes in relation with time at t = 0 (P = 0.008) and t = 4 (P = 0.000). Conclusion Although only drilling without cooling was studied, short drilling times may prevent the disappearance of osteocytes in case cooling is not used in clinical practice as is the case in percutaneous K-wire insertion. PMID:17598116

  1. Indium-111-labeled LDL: A potential agent for imaging atherosclerotic disease and lipoprotein biodistribution

    SciTech Connect

    Rosen, J.M.; Butler, S.P.; Meinken, G.E.; Wang, T.S.; Ramakrishnan, R.; Srivastava, S.C.; Alderson, P.O.; Ginsberg, H.N. )

    1990-03-01

    Radiolabeling of low-density lipoprotein (LDL) and external imaging with a gamma camera would offer a means of taking advantage of the metabolic activity of developing atherosclerotic lesions in order to noninvasively detect and determine the extent of atherosclerotic cardiovascular disease. Indium-111-({sup 111}In) labeled LDL was prepared and its purity demonstrated by agarose electrophoresis and ultracentrifugation. In vitro studies with cultured human fibroblasts demonstrated significant inhibition of iodine-125-({sup 125}I) LDL binding to LDL receptors by {sup 111}In-LDL, although this was less than the inhibition produced by unlabeled LDL. Adrenal gland uptake of {sup 111}In-LDL by hypercholesterolemic rabbits was reduced by 86% compared to the level of uptake observed in normal rabbits. These results were compatible with downregulation of adrenal LDL receptors in the hypercholesterolemic rabbits. Uptake of {sup 111}In-LDL in the atherosclerotic proximal aorta of hypercholesterolemic rabbits was 2.5 times higher than in normal rabbits. These results suggest that {sup 111}In-LDL has the potential to be a useful agent for external imaging of atherosclerotic lesions and lipoprotein biodistribution.

  2. Cyclic Bending Contributes to High Stress in a Human Coronary Atherosclerotic Plaque and Rupture Risk: In Vitro Experimental Modeling and Ex Vivo MRI-Based Computational Modeling Approach.

    PubMed

    Yang, Chun; Tang, Dalin; Kobayashi, Shunichi; Zheng, Jie; Woodard, Pamela K; Teng, Zhongzhao; Bach, Richard; Ku, David N

    2008-01-01

    Many acute cardiovascular syndromes such as heart attack and stroke are caused by atherosclerotic plaque ruptures which often happen without warning. MRI-based models with fluid-structure interactions (FSI) have been introduced to perform flow and stress/strain analysis for atherosclerotic plaques and identify possible mechanical and morphological indices for accurate plaque vulnerability assessment. In this paper, cyclic bending was added to 3D FSI coronary plaque models for more accurate mechanical predictions. Curvature variation was prescribed using the data of a human left anterior descending (LAD) coronary artery. Five computational models were constructed based on ex vivo MRI human coronary plaque data to assess the effects of cyclic bending, pulsating pressure, plaque structure, and axial stretch on plaque stress/strain distributions. In vitro experiments using a hydrogel stenosis model with cyclical bending were performed to observe effect of cyclical bending on flow conditions. Our results indicate that cyclical bending may cause more than 100% or even up to more than 1000% increase in maximum principal stress values at locations where the plaque is bent most. Stress increase is higher when bending is coupled with axial stretch, non-smooth plaque structure, or resonant pressure conditions (zero phase angle shift). Effects of cyclic bending on flow behaviors are more modest (21.6% decrease in maximum velocity, 10.8% decrease in flow rate, maximum flow shear stress changes were < 5%). Computational FSI models including cyclic bending, plaque components and structure, axial stretch, accurate in vivo measurements of pressure, curvature, and material properties should lead to significant improvement on stress-based plaque mechanical analysis and more accurate coronary plaque vulnerability assessment.

  3. Injectable hyaluronic-acid-doxycycline hydrogel therapy in experimental rabbit osteoarthritis

    PubMed Central

    2013-01-01

    Background Osteoarthritis (OA) is a common joint disease that causes disabilities in elderly adults. However, few long-lasting pharmacotherapeutic agents with low side effects have been developed to treat OA. We evaluated the therapeutic effects of intra-articular injections of hydrogels containing hyaluronic acid (HA) and doxycycline (DOX) in a rabbit OA model. Results Thirteen week old New Zealand White rabbits undergone a partial meniscectomy and unilateral fibular ligament transection were administered with either normal saline (NT), HA, DOX or HA-DOX hydrogels on day 0, 3, 6, 9 and 12; animals were also examined the pain assessment in every three days. The joint samples were taken at day 14 post-surgery for further histopathological evaluation. The degree of pain was significantly attenuated after day 7 post-treatment with both HA and HA-DOX hydrogels. In macroscopic appearance, HA-DOX hydrogel group showed a smoother cartilage surface, no or minimal signs of ulceration, smaller osteophytes, and less fissure formation in compare to HA or DOX treatment alone. In the areas with slight OA changes, HA-DOX hydrogel group exhibited normal distribution of chondrocytes, indicating the existence of cartilage regeneration. In addition, HA-DOX hydrogels also ameliorated the progression of OA by protecting the injury of articular cartilage layer and restoring the elastoviscosity. Conclusion Overall, from both macroscopic and microscopic data of this study indicate the injectable HA-DOX hydrogels presented as a long-lasting pharmacotherapeutic agent to apply for OA therapy. PMID:23574696

  4. Remote Subcutaneous Needling to Suppress the Irritability of Myofascial Trigger Spots: An Experimental Study in Rabbits

    PubMed Central

    Fu, Zhonghua; Hsieh, Yueh-Ling; Hong, Chang-Zern; Kao, Mu-Jung; Lin, Jaung-Geng; Chou, Li-Wei

    2012-01-01

    Objective. To obtain electrophysiological effects of Fu's subcutaneous needling (FSN) on needling distance by assessment of endplate noise (EPN) recorded from the myofascial trigger spots (MTrSs) in rabbit skeletal muscle. Method. Eighteen New Zealand rabbits weighing 2.5–3.0 kg were randomly divided into two groups as follows: proximal needling (PN) group and distal needling (DN) group. The needling procedure followed the instructions described by the inventor of FSN, including needling insertion and swaying movement. The amplitudes of EPN on the MTrS region of BF muscle were recorded as an index of MTrS irritability. Random sampling of EPN tracings were taken for further analyses before, during, and after FSN treatment. Results. In PN and DN groups, the trends of EPN amplitude alterations were similar at conditions before, during, and after FSN treatment. The degree of reduction in the EPN amplitude in PN group was significantly higher than that in DN group. There were no significant changes in EPN amplitudes in the MTrS of contralateral BF without FSN intervention either in DN or PN group. Conclusion. The irritability of proximal MTrSs could be modulated after ipsilateral FSNs. The placement of FSN may affect the effectiveness of suppression of irritability of MTrSs. PMID:23346200

  5. [The adrenergic mechanisms are involved in the pulmonary hemodynamics changes following experimental myocardial ischemia in rabbits].

    PubMed

    Evlakhov, V I; Poiasov, I Z

    2012-05-01

    In acute experiments in anesthetized rabbits the changes of the pulmonary hemodynamics following myocardial ischemia in the region of the descendent left coronary artery were studied in control animals and after the blockade of alpha-adrenoreceptors by phentolamine or N-cholinoreceptors of autonomic ganglia by hexamethonium. Following myocardial ischemia in control animals the pulmonary artery pressure and flow decreased, the pulmonary vascular resistance was elevated not significantly, the cardiac output decreased more than pulmonary artery flow. Following myocardial ischemia after the blockade of alpha-adrenoreceptors the pulmonary artery flow and cardiac output decreased in the same level and the pulmonary vascular resistance was decreased. In these conditions the pulmonary artery pressure decreased more than in control animals, meanwhile the pulmonary artery flow was decreased in the same level as in the last case. Following myocardial ischemia after the blockade of N-cholinoreceptors the pulmonary hemodynamics changes were the same as they were following myocardial ischemia in the control rabbits, the cardiac output decreased more than pulmonary artery flow. The disbalance of the cardiac output and pulmonary artery flow changes in the case of myocardial ischemia was caused by the pulmonary vessel reactions following activations of the humoral adrenergic mechanisms.

  6. Novel use of botulinum toxin to ameliorate arthrofibrosis: an experimental study in rabbits.

    PubMed

    Namazi, Hamid; Torabi, Simin

    2007-08-01

    This study aimed to investigate the effects of intra-articular botulinum toxin in preventing arthrofibrosis. Arthrofibrosis was induced in both stifle joints of 20 rabbits by transecting the anterior cruciate ligament under intramuscular anesthesia with ketamine and xylazine. Intra-articular toxin at a dose of 0.6 ml (50 unit) and physiologic saline solution (0.6 ml) were injected into the right and left stifle joints, respectively, 3 times with a 1-week interval between each injection. The rabbits were euthanized in the 12th week via high dose anesthesia to remove the stifle joint. The severity of adhesions was assessed, applying a universal scoring system. Also the stifle joints were histologically evaluated for fibrosis. With regards to severity of adhesion a significant reduction in the adhesion score was observed in the toxin-treated group in comparison to untreated controls with mean +/- SE values of 0.2 +/- 0.1 and 2.4 +/- 0.2, respectively (p < 0.01). The histological evaluation showed no significant fibroblast in the toxin-treated group versus dense fibers with mature fibroblasts in the control group. Our results suggest that botulinum toxin demonstrated efficacy in preventing adhesion after knee surgery and all the parameters monitored showed consistent statistically significant improvement.

  7. Treatment of endometriosis with local acetylsalicylic acid injection: experimental study in rabbits.

    PubMed

    Siqueira, Juliana Menezes; Barreto, Adriana Beatriz; Saad-Hossne, Rogério

    2011-01-01

    The objective of the present study was to estimate the effects of introduction of acetylsalicylic acid solution into peritoneal implants in autologous endometrium as a method for treating endometriosis. Forty adult female rabbits were subdivided into 4 groups of 10 rabbits each, and endometriosis was induced via autotransplantation of endometrial fragments into the peritoneal cavity. At 30 days after induction of endometriosis, all animals were randomly assigned to 1 of 2 protocols. In protocol 1, animals were evaluated at 24 hours after treatment; group 1 (control) received physiologic solution, and group 2 received acetylsalicylic acid. In protocol 2, animals were evaluated at 10 days after treatment, group 3 (control) and group 4 received acetylsalicylic acid. After measuring the lesion, the endometriotic focus was removed and prepared for mounting on slides for histologic analysis. Imaging software was used for analysis of the total remaining area of endometrial tissue. The affected area in acetylsalicylic acid-treated animals was smaller than that in control animals at 24 hours and 10 days after treatment; a significant difference was found between control and treated groups (p < .001). Statistical analysis comparing protocols 1 and 2 demonstrated no differences between controls groups or acetylsalicylic acid groups (p = .30), and no differences between times (p = .75). Acetylsalicylic acid solution led to less growth (or higher involution) of endometrial implants. Acetylsalicylic acid injected directly into endometriotic foci was effective in their destruction. This presents new perspectives for treatment of endometriosis and for clinical applications based on further clinical studies.

  8. Pathomorphological pattern of paravertebral muscles of rabbits after long-term experimental electrostimulation.

    PubMed

    Szarek, Józef; Kowalski, Ireneusz M; van Dam, Floris; Zarzycki, Daniel; Pawlicki, Roman; Fabczak, Jacek

    2003-01-01

    The objective of this study was to identify the histopathological features of paravertebral muscles after long-term Lateral Electrical Surface Stimulation (LESS). LESS has been applied for the treatment of idiopathic scoliosis in children and adolescents. Former studies reported the negative effect on the mental state of treated patients, as well as functional disturbances of organs, endocrine glands, and muscle metabolism. The experiment was performed on rabbits (aged 3.5 months), (n = 5 in treated, n = 5 in non-treated group). Stimulation was performed using electrical stimulator SCOL-2. The rabbits were stimulated with the traditional long-term lateral electrical surface stimulation (LESS) method as in clinical applications for children and adolescents. After microscopic examination, atrophy of fibers and cross striation of paravertebral muscles were seen, as well as degenerative lesions, necrosis, and hyperemia. Furthermore, proliferation of nuclei and infiltration of monocytogenic phagocytes mononuclear cells were observed, as well as a wide differentiation of glycosoaminoglycanes in muscle fibers on the stimulated side. However, within the tissue undergoing regression, this resulted in a clear decrease in glycosoaminoglycane levels. The observed lesions may indicate that the damage to the neuromuscular system is an effect of long-term LESS application. Thus, standard LESS therapy may deepen idiopathic scoliosis.

  9. Effect of virgin fatty oil of Pistacia lentiscus on experimental burn wound's healing in rabbits.

    PubMed

    Djerrou, Zouhir; Maameri, Z; Hamdi-Pacha, Y; Serakta, M; Riachi, F; Djaalab, H; Boukeloua, A

    2010-04-03

    This study aimed to assess the efficiency of the virgin fatty oil of Pistacia lentiscus (PLVFO) for burn wounds healing. It was carried out on 6 adult male New Zealand rabbits. Four burn wounds of deep third degree were made on the back of each animal. The first was not treated and served as control (CRL group); the others were covered immediately after burning procedure by 0.5g of one of the following products: Vaseline gel (VAS group), Madecassol(®) cream 1% (MAD group) or 1ml of PLVFO (PLVFO group). The treatments were repeated once daily until complete healing. For four days post burns, the percentage of wound contraction was assessed. Also, the different healing times were noted. The results showed that both PLVFO and Madecassol(®) significantly accelerated wound healing activity compared to wounds dressed with Vaseline and the untreated wounds. However, the level of wound contraction was significantly higher and the healing time was faster in PLVFO group than those of the MAD group, VAS group and CRL group. The different epithelization periods obtained in days were respectively: 30±3.94 (PLVFO group), 33.5±3.78 (MAD group), 34.66±3.88 (VAS group) and 37.16±3.54 (CRL group). We conclude that Pistacia lentiscus virgin fatty oil promotes significantly (p< 0.05) wound contraction and reduces epithelization period in rabbit model.

  10. Influence of soft tissue contamination on the integration of titanium implants. An experimental study in rabbits.

    PubMed

    Ivanoff, C J; Sennerby, L; Lekholm, U

    1996-06-01

    In the present study, the influence of peroperative soft tissue contamination on the healing of titanium implants was studied in 9 lop-eared rabbits. Titanium implants (Brånemark System) were inserted in the tibiae, a location with cortical bone only, in such a way that one group was inserted the standard way (control), and another group was contaminated for 30 s in the adjacent soft tissues, prior to insertion. The implants were allowed to heal for 12 weeks and were then retrieved together with surrounding bone, fixed, dehydrated and embedded in plastic resin. About 10 micron thick ground sections were prepared for light microscopic morphometry. The mineralized bone-to-titanium contact, and the amount of bone occupying the threads, were calculated for each implant, and the results of the two groups were compared. All retrieved implants were clinically stable at the end of the experiment. Regarding bone-to-titanium contact and bone area within the threads, a statistically nonsignificant difference was observed between the 2 groups. This study indicated that peroperative soft tissue contamination of c.p. titanium implants does not prevent osseointegration from occurring, when studied in the rabbit tibia.

  11. Influence of implant diameters on the integration of screw implants. An experimental study in rabbits.

    PubMed

    Ivanoff, C J; Sennerby, L; Johansson, C; Rangert, B; Lekholm, U

    1997-04-01

    The influence of diameter on the integration of titanium screw-shaped implants was studied in the rabbit tibia by means of removal torque measurements and histomorphometry. Implants 3.0, 3.75, 5.0, and 6.0 mm in diameter and 6.0 mm long were inserted through one cortical layer in the tibial metaphyses of nine rabbits and allowed to heal for 12 weeks. The implants were then unscrewed with a torque gauge, and the peak torque required to shear off the implants was recorded. The histologic analysis in undemineralized ground sections comprised (1) a gross description of the implant sites and assessments of (2) the total implant length in bone and (3) in the cortical passage, as well as (4) the thickness of the cortical bone adjacent to the implants. From the removal torque values obtained and morphometric measurements, a mean shear stress value was calculated for each implant type. The biomechanical tests showed a statistically significant increase of removal torque with increasing implant diameter. The resistance to shear seemed to be determined by the implant surface in supportive cortical bone, whereas the newly formed bone at the periosteal and endosteal surfaces did not seem to have any supportive properties after 12 weeks. It is suggested that wide diameter implants may be used clinically to increase implant stability.

  12. Experimental infection of the rabbit tick, Haemaphysalis leporispalustris, with the bacterium Rickettsia rickettsii, and comparative biology of infected and uninfected tick lineages.

    PubMed

    Freitas, Luciana Helena T; Faccini, João Luiz H; Labruna, Marcelo B

    2009-04-01

    The present study consisted of two experiments that evaluated experimental infections of Haemaphysalis leporispalustris ticks by a Brazilian strain of Rickettsia rickettsii, and their effect on tick biology. In experiment I, ticks were exposed to R. rickettsii during the larval, nymphal or adult stages by feeding on rabbits (Oryctolagus cuniculus) needle-inoculated with R. rickettsii, and thereafter reared on uninfected rabbits for the entire next tick generation. Regardless of the tick stage that acquired the infection, all subsequent tick stages were shown to be infected by PCR (infection rates varying from 1.3 to 41.7%), and were able to transmit R. rickettsii to uninfected rabbits, as demonstrated by rabbit seroconversion, guinea pig inoculation with rabbit blood, and PCR on rabbit blood. In Experiment II, ticks were exposed to R. rickettsii during the larval stage by feeding on rabbits co-infested with R. rickettsii-infected adult ticks, and thereafter reared on uninfected rabbits until the next generation of larvae. Again, all subsequent tick stages were shown to be infected by PCR (infection rates varying from 3.0 to 40.0%), and were able to transmit R. rickettsii to uninfected rabbits. Thus, it was demonstrated that larvae, nymphs, and adults of H. leporispalustris were able to acquire and maintain the R. rickettsii infection by transstadial and transovarial transmissions within the tick population, with active transmission of the bacterium to susceptible rabbits by all parasitic stages. Analyses of biological parameters of uninfected and R. rickettsii-infected tick lineages were performed in order to evaluate possible deleterious effects of R. rickettsii to the infected tick lineages. Surprisingly, all but one of the four R. rickettsii-experimental groups of the present study showed overall better biological performance than their sibling uninfected control ticks. Results of the present study showed that H. leporispalustris could support infection by a

  13. Efficacy, plasma pharmacokinetics, and safety of icofungipen, an inhibitor of Candida isoleucyl-tRNA synthetase, in treatment of experimental disseminated candidiasis in persistently neutropenic rabbits.

    PubMed

    Petraitiene, Ruta; Petraitis, Vidmantas; Kelaher, Amy M; Sarafandi, Alia A; Mickiene, Diana; Groll, Andreas H; Sein, Tin; Bacher, John; Walsh, Thomas J

    2005-05-01

    Icofungipen (formerly PLD-118) is a synthetic derivative of the naturally occurring beta-amino acid cispentacin that blocks isoleucyl-tRNA synthetase, resulting in the inhibition of protein synthesis and growth of fungal cells. We investigated the efficacy, plasma pharmacokinetics, and safety of icofungipen in escalating dosages for the treatment of experimental subacute disseminated candidiasis in persistently neutropenic rabbits. Icofungipen was administered for 10 days starting 24 h after the intravenous inoculation of 10(3) Candida albicans blastoconidia. Study groups consisted of rabbits treated with icofungipen at 4 (ICO-4), 10 (ICO-10), and 25 (ICO-25) mg/kg of body weight/day in two divided dosages, rabbits treated with fluconazole at 10 mg/kg/day, rabbits treated with amphotericin B at 1 mg/kg/day, and untreated controls. Levels of icofungipen in plasma were derivatized by phthaldialdehyde and quantified by high-performance liquid chromatography with fluorescence detection. Rabbits treated with ICO-10 (P < 0.01) and ICO-25 (P < 0.001) showed significant dosage-dependent tissue clearance of C. albicans from the liver, spleen, kidney, brain, vitreous, vena cava, and lung in comparison to untreated controls. ICO-25 cleared C. albicans from all tissues and had activity comparable to that of amphotericin B versus untreated controls (P < 0.001). Pharmacokinetics of icofungipen in plasma approximated a dose-dependent relationship of the maximum concentration of drug in serum and the area under the concentration-time curve. There was no significant elevation of the levels of hepatic transaminases, alkaline phosphatase, bilirubin, urea nitrogen, or creatinine in icofungipen-treated rabbits. Icofungipen followed dose-dependent pharmacokinetics and was effective in the treatment of experimental disseminated candidiasis, including central nervous system infection, in persistently neutropenic rabbits.

  14. Pectin nanocoating of titanium implant surfaces - an experimental study in rabbits.

    PubMed

    Gurzawska, Katarzyna; Dirscherl, Kai; Jørgensen, Bodil; Berglundh, Tord; Jørgensen, Niklas Rye; Gotfredsen, Klaus

    2017-03-01

    A major determinant of successful osseointegration of endosseous implants is the surface of the implant, which influences the cellular response of the surrounding tissues. A new strategy to improve osseointegration and bone healing is biochemical stimulation by surface nanocoatings that may increase adhesion of bone proteins, and bone cells at the implant surface. Nanocoating with pectins, plant cell wall-derived polysaccharides, is frequently done using rhamnogalacturonan-I (RG-I). The aim of the study was to evaluate the effect of nanocoating titanium implants with plant cell wall-derived rhamnogalacturonan-I, on bone healing and osseointegration. Machined titanium implants were coated with three modifications of rhamnogalacturonan-I (RG-I). Chemical and physical surface properties were examined before insertion of nanocoated implants (n = 96) into the left and right tibia of rabbits. Machined titanium implants without RG-I nanocoating were used as controls (n = 32). Total number of 128 implants was placed in tibias of 16 rabbits. Fluorochrome bone labels, calcein green and alizarin red S were given intravenously after 9 and 12 days, respectively. The bone response to the nanocoated implants was analyzed qualitatively and quantitatively after 2, 4, 6, and 8 weeks of healing using light microscopy and histomorphometric methods. The RG-I coating influenced the surface chemical composition; wettability and roughness, making the surface more hydrophilic without any major effect on surface micro roughness compared to control implant surfaces. The different modifications of pectin RG-I did not significantly enhance bone healing and osseointegration analyzed after 2, 4, 6, and 8 weeks of healing compared to control implants. Although the qualitative analyses of the fluorochromes indicated a higher activity of bone formation in the mineralization front at the early stage, after 9 and 12 days at the RG-I nanocoated implants compared to the control implants

  15. New bone formation in bone defects after melatonin and porcine bone grafts: experimental study in rabbits.

    PubMed

    Calvo-Guirado, José-Luis; Gómez-Moreno, Gerardo; Maté-Sánchez, José-Eduardo; López-Marí, Laura; Delgado-Ruiz, Rafael; Romanos, Georgios E

    2015-04-01

    The aim of this study was to evaluate the effect of the topical application of melatonin compared with collagenized porcine bone grafts to accelerate bone formation 2 months after their insertion in tibiae rabbits. Twenty New Zealand rabbits weighing 3,900-4,500 g were used. Twenty collagenized porcine bone (MP3) grafts, twenty melatonin-impregnated bone grafts, and twenty control areas were placed in the proximal metaphyseal area of both rear tibias. Four groups were formed according to the moment in which animal killing was carried out: Group I (15 days), Group II (30 days), Group III (45 days) and Group IV (60 days). Cortical width and cortical length of bone formation was measured. Following implantation, an anteroposterior and lateral radiological study was carried out. Samples were sectioned at 5 μm and stained using hematoxylin-Eeosin, Masson's trichromic, and Gordon-Switt reticulin stains. After 60 days of treatment period, melatonin increased the length of cortical bone formation 99.03 ± 0.61% like control 98.90 ± 3.82% compared with porcine bone 92.73 ± 1.08%. Related to perimeter of cortical bone of the tibiae melatonin new bone was 98.35 ± 1.14% like control 98.0 ± 1.43% more than porcine bone 92.05 ± 1.03%. Histomorphometric values related to porcine bone were connective tissue 49.16 ± 2.4%, graft material (MP3) 23.52 ± 2.3%, and new bone formation 27.32 ± 1.4% compared with test group with melatonin 24.5 ± 1.2%, connective tissue 45.1 ± 1.2%, and new bone formation of 30.4 ± 1.0%. Melatonin has proven to regenerate the width and length of cortical bone in tibiae rabbits more quickly than collagenized porcine bone. Melatonin acts as a bone stimulator compared with porcine bone and control sites. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Experimental urethane anaesthesia prevents digoxin intoxication: electrocardiographic and histological study in rabbit.

    PubMed

    Princi, T; Delbello, G; Grill, V

    2000-10-01

    An electrocardiographic and histological study was performed in rabbit to detect the effects of urethane (ethyl carbamate) intraperitoneal (i.p.) anaesthesia in digoxin intoxication, since it has been previously shown that this anaesthetic and digitalis glycosides exert specific peripheral effects on the cardiovascular system involving central structures of the autonomic nervous system. We observed that i.p. urethane anaesthesia prevented the onset of the electrocardiographic signs of digitalis intoxication, as well as inhibiting the appearance of histological myocardial alterations after treatment with toxic digoxin doses. On the other hand, lethal arrhythmias and severe myocardial damage were observed in animals that had not undergone preliminary urethane anaesthesia. These results indicate that the effect exerted by urethane in preventing the toxic action of digoxin is probably due to a decrease of sympathetic activity in anaesthetized animals by centrally mediated sympathetic inhibition. Copyright 2000 Academic Press.

  17. Miragel versus silastic used as episcleral implants in rabbits. An experimental and histopathologic comparative study.

    PubMed

    D'Hermies, F; Korobelnik, J F; Savoldelli, M; Chauvaud, D; Pouliquen, Y

    1995-01-01

    Tissue reactions to two different biomaterials implanted on the sclera of rabbit eyes, a silicone implant (Silastic; Dow Corning) and a hydrogel (Miragel; Mira Inc.), were evaluated. Both materials were implanted on the scleral surface under the superior rectus to obtain a focal scleral buckling. Histopathologic examination of the 32 eyes was performed with transmission electron microscopy 5 to 8 months after implantation. During the follow-up period, 6 silicone implants were extruded, compared with only one hydrogel implant. Histopathologically, both types of implants were surrounded by a newly formed fibrous capsule. Only the hydrogel implant gave rise to a granulomatous foreign body reaction against its own fragments, however. The main difference between the two types of material was a superficial fragmentation of the hydrogel implants. The reason for this fragmentation is unknown. To our knowledge, this is the first reported case of foreign body giant cell granuloma that developed against a hydrogel implant.

  18. Experimental aluminum pathology in rabbits: effects of hydrophilic and lipophilic compounds.

    PubMed Central

    Bombi, G G; Corain, B; Favarato, M; Giordano, R; Nicolini, M; Perazzolo, M; Tapparo, A; Zatta, P

    1990-01-01

    Aluminum lactate [Al(lact)3] (hydrophilic, hydrolytically unstable) and aluminum acetylacetonate [Al(acae)3] (lipophilic, hydrolytically stable) were tested as potential toxicants to rabbits upon IV administration both as aqueous solutions and as liposome suspensions. Both chemicals behaved as cardiotoxic agents when administered as aqueous solutions, but Al(acae)3 was at least two orders of magnitude more active than Al(lact)3. Al(acae)3, but not Al(lact)3, caused myocardial infarcts resembling those in humans (with contraction bands) at doses as low as 0.24 mg/kg body weight, as well as a prominent acanthocytosis. Al(lact)3, when administered as a liposome suspension, was about 300 times more toxic than in aqueous solution, although cardiac damage was not infarctual in character. Both chemical and physical speciation of aluminum(III) thus play an essential role in determining the toxicity of the metal. Images FIGURE 2. FIGURE 3. PMID:2088750

  19. Experimental chronic obstructive lung disease. I. Bronchopulmonary changes induced in rabbits by prolonged exposure to formaldehyde.

    PubMed

    Ionescu, J; Marinescu, D; Tapu, V; Eskenasy, A

    1978-01-01

    The prolonged exposure to formaldehyde induces in the rabbit lung reactional and dystrophic changes involving the intrapulmonary bronchi, the bronchioli and the lung tissue. These changes are represented by bronchial cell hyperplasia with hypermucigenesis, extrusion of bronchial cells, bronchiolar hypermucigenesis, parcellary squamous metaplasia or necrobiosis of epithelia, thickening of bronchial and bronchiolar walls by subepithelial cell accumulations, destruction of musculo-elastic structures with stenosis or ectasia; the vascular reactions are hyperhaemic and proliferative with an obstructive and fibrous tendency; the parenchymal lesions are atelectasias, intralobular emphysema, and cellular thickening of alveolar walls and interlobular areas. The acid phosphatase, Tween-60-esterase, naphthol-AS-D-acetate-esterase, proline-oxidase and hydroxyproline-2-epimerase activities are increasing, while the leucyl-aminopeptidase and beta-glucuronidase ones are decreasing. The qualitative observations are completed and sustained by quanitative studies of mucous cell kinetics, of cell accumulations and differentiations.

  20. Repair of experimentally produced defects in rabbit articular cartilage by autologous chondrocyte transplantation

    SciTech Connect

    Grande, D.A.; Pitman, M.I.; Peterson, L.; Menche, D.; Klein, M.

    1989-01-01

    Using the knee joints of New Zealand White rabbits, a baseline study was made to determine the intrinsic capability of cartilage for healing defects that do not fracture the subchondral plate. A second experiment examined the effect of autologous chondrocytes grown in vitro on the healing rate of these defects. To determine whether any of the reconstituted cartilage resulted from the chondrocyte graft, a third experiment was conducted involving grafts with chondrocytes that had been labeled prior to grafting with a nuclear tracer. Results were evaluated using both qualitative and quantitative light microscopy. Macroscopic results from grafted specimens displayed a marked decrease in synovitis and other degenerative changes. In defects that had received transplants, a significant amount of cartilage was reconstituted (82%) compared to ungrafted controls (18%). Autoradiography on reconstituted cartilage showed that there were labeled cells incorporated into the repair matrix.

  1. Leukocyte and /sup 67/Ga-citrate dynamics in experimental subcutaneous Streptococcus faecalis infections. [Rabbits

    SciTech Connect

    Tight, R.R.; Siddiqui, A.R.

    1981-07-01

    The dynamics of white blood cell (WBC) and /sup 67/Ga-citrate accumulation were studied in rabbits with subcutaneous polyethylene chambers. Uninfected chamber fluid (CF) contained <1000 WBCs/mm/sup 3/, most of which were mononuclear. After /sup 67/Ga injection, radioactivity increased slowly in uninfected fluid, peaked between 24 and 48 hours, and then gradually decreased. /sup 67/Ga scans showed no uptake in excess of background levels around the uninfected chambers. After injection of Streptococcus faecalis directly into the chambers, bacterial concentrations initially decreased, increased by 4 to 24 hours, and then decreased slightly. WBCs began to increase 4 hours after infection due to influx of polymorphonuclear leukocytes. /sup 67/Ga localized in infected chambers before the increase in WBCs. Use of the subcutaneous chamber model could help elucidate the mechanism(s) of /sup 67/Ga accumulation at sites of in flammation.

  2. Increased IL-37 in Atherosclerotic Disease could be Suppressed by Atorvastatin Therapy.

    PubMed

    Shaoyuan, C; Ming, D; Yulang, H; Hongcheng, F

    2015-10-01

    Recently, the evidence showed that interleukin-37 (IL-37) was expressed in the foam-like cells of atherosclerotic coronary and carotid artery plaques in IL-37-transgenic mice, suggesting that interleukin-37 is involved in atherosclerosis-related diseases. The purpose of this study was to determine the change of IL-37 in atherosclerotic plaque, the effect of atorvastatin on IL-37 and the association between IL-37 and Smad3 in atherosclerotic disease. Rabbits were subjected to atherosclerosis by the immunologic injury composite with balloon injury (BI). Some rabbits received atorvastatin treatment from 6 weeks to 12 weeks. Serum levels of IL-37 were assessed at baseline, 6 weeks and 12 weeks in normal, atherosclerotic and atorvastatin groups. Protein and RNA levels of IL-37 atherosclerotic plaque from abdominal aorta were processed at 12 weeks. Abdominal aorta including atherosclerotic plaque was immunostained with IL-37 and Smad3. Serum IL-37 significantly increased in atherosclerotic disease, and this increase could be reduced by the atorvastatin treatment. IL-37 and Smad3 were accumulated in the macrophage-derived foam cells in the plaque and significantly increased in protein and RNA levels. Atorvastatin treatment could significantly suppress the increase of both IL-37 and Smad3. Plasma level of IL-37 and the IL-37 expression of the plaque were significantly increased in atherosclerotic disease. This increase could be suppressed by the atorvastatin treatment. In addition, Smad3 might be required for IL-37 activity during the atherosclerotic physiologic process. © 2015 The Foundation for the Scandinavian Journal of Immunology.

  3. Trimethoprim-sulfamethoxazole therapy of experimental Escherichia coli meningitis in rabbits.

    PubMed Central

    Mylotte, J M; Bates, T R; Sergeant, K A; Matson, R E; Beam, T R

    1981-01-01

    We used two strains of ampicillin-susceptible Escherichia coli to produce meningitis in rabbits and utilized these models (i) to compare the killing effects of parenteral trimethoprim-sulfamethoxazole (TMP-SMZ) and ampicillin on E. coli in cerebrospinal fluid after 8 h of treatment and (ii) to measure the penetration of TMP-SMZ and ampicillin into cerebrospinal fluid and the brain. At 16 h after intracisternal inoculation with a test strain, rabbits were treated with TMP (6 mg/kg per h) and SMZ (30 mg/kg per h), ampicillin (40 mg/kg per h), or saline intravenously for 8 h. TMP-SMZ levels were measured by high-pressure liquid chromatography, and ampicillin levels were measured by microbiological assay. Mean +/- standard deviation concentrations of TMP, SMZ, and ampicillin in cerebrospinal fluid (mean percent penetration) at the completion of 8 h of therapy were 0.80 +/- 0.41 (18%), 15.7 +/- 21.1 (27.2%), and 2.6 +/- 1.7 (8.9%) microgram/ml, respectively. TMP, SMZ, and ampicillin levels in brain homogenate after 8 h of therapy were 0.23 +/- 0.07 (6.6%), 3.31 +/- 3.3 (5.5%), and 0.6 +/- 4.53 (1.9%) microgram/g, respectively. TMP-SMZ infusion for 8 h produced a significant reduction in mean bacterial counts in cerebrospinal fluid in both models of meningitis compared with saline controls. The decrease in mean bacterial counts with TMP-SMZ therapy was equivalent to that produced by ampicillin. PMID:7025751

  4. Survival of block and fascial-wrapped diced cartilage grafts: an experimental study in rabbits.

    PubMed

    Fatemi, Mohammad Javad; Hasani, Mohammad Esmaeel; Rahimian, Shahram; Bateni, Hamid; Pedram, Mirsepehr; Mousavi, Seyed Jaber

    2012-09-01

    Cartilage grafts have become an integral part in plastic surgery. Classic autogenous cartilage harvesting techniques are associated with significant donor- and recipient-site morbidity. The use of cartilage micrografts wrapped in a sleeve was first developed to decrease the complication rates of block cartilage grafts. The aim of this study was to compare the resorption rate of solid block cartilage graft and diced cartilage wrapped in fascia graft in rabbits. In 12 rabbits, 1 solid block cartilage and 1 diced graft wrapped in fascia were implanted in subcutaneous pockets. By the end of the fourth month, the cartilage implants were dissected free and photographed and weighed exactly. Then specimens were stained with hematoxylin and eosin to determine their architectural characteristics. In the solid block cartilage graft group, the means ± standard deviation preimplant weight values were 5.34 ± 1.68. The weight was changed to 7.74 ± 3.26. The change was not statistically significant. In diced cartilage grafts wrapped in fascia, the means ± standard deviation preimplanted weight values were 8.13 ± 1.83. These values were changed to 2.79 ± 1.97, meaning statistically significant resorption of diced cartilage grafts wrapped in fascia (P < 0.001). In histologic examination, block cartilage grafts showed viable cartilage but diced cartilage grafts wrapped in fascia yielded fibrosis and inflammatory cell infiltration. The amplitude of resorption of the diced cartilage wrapped in fascia is considerable compared with one-piece block grafts. It may be anticipated that the enthusiasm for this technique will decline once the long-term results of pertaining clinical studies are available.

  5. Detection of pulmonary fat embolism with dual-energy CT: an experimental study in rabbits.

    PubMed

    Tang, Chun Xiang; Zhou, Chang Sheng; Zhao, Yan E; Schoepf, U Joseph; Mangold, Stefanie; Ball, B Devon; Han, Zong Hong; Qi, Li; Zhang, Long Jiang; Lu, Guang Ming

    2017-04-01

    To evaluate the use of dual-energy CT imaging of the lung perfused blood volume (PBV) for the detection of pulmonary fat embolism (PFE). Dual-energy CT was performed in 24 rabbits before and 1 hour, 1 day, 4 days and 7 days after artificial induction of PFE via the right ear vein. CT pulmonary angiography (CTPA) and lung PBV images were evaluated by two radiologists, who recorded the presence, number, and location of PFE on a per-lobe basis. Sensitivity, specificity, and accuracy of CTPA and lung PBV for detecting PFE were calculated using histopathological evaluation as the reference standard. A total of 144 lung lobes in 24 rabbits were evaluated and 70 fat emboli were detected on histopathological analysis. The overall sensitivity, specificity and accuracy were 25.4 %, 98.6 %, and 62.5 % for CTPA, and 82.6 %, 76.0 %, and 79.2 % for lung PBV. Higher sensitivity (p < 0.001) and accuracy (p < 0.01), but lower specificity (p < 0.001), were found for lung PBV compared with CTPA. Dual-energy CT can detect PFE earlier than CTPA (all p < 0.01). Dual-energy CT provided higher sensitivity and accuracy in the detection of PFE as well as earlier detection compared with conventional CTPA in this animal model study. • Fat embolism occurs commonly in patients with traumatic bone injury. • Dual-energy CT improves diagnostic performance for pulmonary fat embolism detection. • Dual-energy CT can detect pulmonary fat embolism earlier than CTPA.

  6. [Experimental study of poly-DL-lactic acid membrane guided bone regeneration in rabbit radii bone defects].

    PubMed

    Duan, Hong; Fan, Yubo; Dou, Jun; Pei, Fuxing

    2004-10-01

    This study was conducted to observe bone regeneration guided by poly-DL-latic acid (PDLLA) membrane in rabbit radii bone defects and to explore the mechanism of the membrane guided bone regeneration (MGBR). The animal models of bony and periosteous defects were established in both radii of 40 adult New Zealand white rabbits. The left defect as the experimental side was bridged with PDLLA membrane tube, the right side as the controlled side was untreated. The specimens were collected at 2, 4, 8 and 12 weeks postoperatively. General observation, X-ray, histological observation and biomechanical examination were applied to the repair of the models of MGBR in both groups. Two weeks after operation, with much new bony callus formed outside the tube at both fragments, the membrane tube covered with connective tissues was filled with haematoma and fibrous callus. Twelve weeks after operation, the PDLLA membrane became white and its tube shape was still maintained. However, new bone callus outside the tube almost completely disappeared, and inside the tubes all radii bone defects were successfully repaired with bony union. On the controlled sides, bone defects were filled with connective tissues 2 weeks postoperatively. And 12 weeks after operation, the typical nonunion that had been formed after bone marrow canals were sealed with cortical bone. On the experimental side, the strength of the newly formed bone at the 12th week was higher than that at the 8th week (P<0.05), whereas the biomechanical examination could not be done on the controlled side. Therefore, these findings suggested that the bone regeneration could be successfully guided by PDLLA membrane, and this MGBR technique might be generally used in the treatment of bone defects and nonunion.

  7. Microbiologic, Pharmacokinetic, and Clinical Effects of Corneal Collagen Cross-Linking on Experimentally Induced Pseudomonas Keratitis in Rabbits.

    PubMed

    Cosar, C Banu; Kucuk, Mutlu; Celik, Ekrem; Gonen, Tansu; Akyar, Isin; Serteser, Mustafa; Tokat, Fatma; Ince, Umit

    2015-10-01

    To determine the effects of corneal collagen cross-linking (CXL) on the penetration of topical 0.5% moxifloxacin, on the number of colony-forming units (CFUs) in the cornea, and on the clinical course in a rabbit eye model of experimentally induced Pseudomonas aeruginosa keratitis. In this prospective animal study, experimental Pseudomonas corneal ulcers were induced in 56 corneas of 28 albino New Zealand rabbits. The corneas were randomly divided into the following 4 groups: the control group (14 eyes), the MOX group (moxifloxacin) (14 eyes), the MOX + CXL group (14 eyes), and the CXL group (14 eyes). On day 4 of the experiment, the eyes in the control group were enucleated and CFU counting was performed. On day 10 of the experiment, all eyes were enucleated and CFU counting was performed. In the MOX and MOX + CXL groups, the moxifloxacin level in the cornea, aqueous humor, iris, plasma, and serum was measured by reverse-phase high-performance liquid chromatography. The difference in the corneal CFU count between the MOX group and the MOX + CXL group was not significant (P = 0.317). Clinical improvement was greatest in the MOX + CXL group (P < 0.001). The mean corneal moxifloxacin level was 0.391 ± 0.09 μg·mg in the MOX group versus 0.291 ± 0.09 μg·mg in the MOX + CXL group; as such, CXL did not have a significant effect on antibiotic penetrance (P = 0.386). Clinical improvement was greatest in the MOX + CXL group. The synergistic effect of CXL on corneal ulcer treatment is not through antibiotic penetrance.

  8. Excimer laser "corneal shaping": a new technique for customized trephination in penetrating keratoplasty. First experimental results in rabbits.

    PubMed

    Schmitz, Klaus; Schreiber, Wolfram; Behrens-Baumann, Wolfgang

    2003-05-01

    The aim of the presented experimental work was to develop a technique for congruent trephination of donor and recipient corneas in free form using a 193-nm excimer laser and to study the clinical follow-up after the application of the technique in a rabbit model. In 12 New Zealand White rabbits homologous penetrating keratoplasty was performed. Trephination of donor buttons and recipient beds was achieved in six animals by conventional mechanical trephination and in six by excimer laser trephination with a guided laser beam in a non-circular geometry. The surgical procedure and its applicability to human subjects were evaluated and the postoperative clinical course was followed for 6 months. The surgical procedure of full-thickness excimer laser trephination could be performed reproducibly in the animal model both for dissection of the donor buttons and for preparation of the recipient beds. Keratoplasty was performed with kidney-shaped transplants after trephination in free form with the guided laser beam. Postoperative clinical follow-up did not show any differences between the two trephination groups that could be related to the applied trephination technique. After 6 months we observed well-adapted and clear corneal grafts, kidney-shaped in the excimer trephination group and circular in the mechanical trephination group. No side effects on the crystalline lens and the central retina could be clinically observed following excimer laser trephination. We present the first experimental study of keratoplasty with freely selected transplant geometry and perfect congruence of donor button and recipient bed. The application of this technique in certain corneal disorders in humans will offer improved treatment options in the future.

  9. Study of wound-healing activity of bioregulators isolated from eye tissues and bovine serum in the model of experimental corneal injury in rabbits in vivo.

    PubMed

    Konstantinovsky, A A; Krasnov, M S; Yamskova, V P; Rybakova, E Yu; Yamskov, I A

    2012-06-01

    We compared wound-healing activity of bioregulators isolated from cattle cornea, serum, and retinal pigment epithelium on in vivo model of experimental corneal injury in rabbits. Bioregulators were instilled into the eye as solutions at a concentration corresponding to 10(-12) mg protein/ml. The animals were sacrificed on day 21 after injury and the corneas were examined histologically. The best wound-healing effect was produced by bioregulators isolated from the cornea and serum and instilled successively into rabbit eyes with an interval of 15-20 min twice a day: multicellular epithelium was observed in the wound, and slight inflammation, in the stroma.

  10. Hormonal and behavioral changes induced by acute and chronic experimental infestation with Psoroptes cuniculi in the domestic rabbit Oryctolagus cuniculus

    PubMed Central

    2013-01-01

    Background Parasitic diseases are important in animal production because they cause high economic losses. Affected animals often exhibit stereotypical behavioral alterations such as anorexia and inactivity, among others. Among the diseases that commonly affect domestic rabbits is mange, which is caused by the mite Psoroptes cuniculi. Therefore, within the context of the host-parasite relationship, it is critical to understand the mechanisms involved in the alteration of host behavior, in order to better utilize sick animal behavior as a strategy for diagnosis and treatment of disease. Methods Rabbits were infested placing mites in the ear conduct. We characterized changes in exploratory behavior and scent marking evoked by acute (1-9 days) and chronic (25-33 days) experimental infestation. Behavior was recorded during ten minutes while the animals were in a 120 cm × 120 cm open field arena divided into 9 squares. Serum cortisol was measured individually using radioimmunoassay kits. Locomotor activity, chinning, rearing and body weight were compared using a Friedman test, the effect of treatment (infested versus non-infested) across time was analyzed using a repeated measures ANOVA, and the Pearson test was used to determine whether chinning and ambulation scores were significantly correlated. Serum cortisol levels and food consumption were analyzed with a Kruskal-Wallis test and body temperature was analyzed with an ANOVA test. Results We observed a significant decrease in rearing behavior as early as two days post-infestation, while chinning and locomotor activity were significantly decreased four days post-infestation. Chronic infestation was associated with decreased food intake, significant weight loss, and a trend toward increased serum cortisol levels, while no changes were observed in body temperature. Conclusions The presence of visible lesions within the ear canal is commonly used to detect mite infestation in rabbits, but this is possible only after

  11. Antirestenotic effects of a novel polymer-coated d-24851 eluting stent. Experimental data in a rabbit iliac artery model.

    PubMed

    Lysitsas, Dimitrios N; Katsouras, Christos S; Papakostas, John C; Toumpoulis, Ioannis K; Angelidis, Charalampos; Bozidis, Petros; Thomas, Christopher G; Seferiadis, Konstantin; Psychoyios, Nikolaos; Frillingos, Stathis; Pavlidis, Nikolaos; Marinos, Euaggelos; Khaldi, Lubna; Sideris, Dimitris A; Michalis, Lampros K

    2007-01-01

    Experimental and clinical data suggest that stents eluting antiproliferative agents can be used for the prevention of in-stent restenosis. Here we investigate in vitro the antiproliferative and apoptotic effect of D-24851 and evaluate the safety and efficacy of D-24851-eluting polymer-coated stents in a rabbit restenosis model (n = 53). Uncoated stents (n = 6), poly (DL: -lactide-co-glycolide) (PLGA)-coated stents (n = 7), and PLGA-coated stents loaded with 0.08 +/- 0.0025 microM (31 +/- 1 mug; low dose; n = 7), 0.55 +/- 0.02 microM (216 +/- 8 mug; high dose; n = 6), and 4.55 +/- 0.1 microM (1774 +/- 39 mug; extreme dose; n = 5) of D-24851 were randomly implanted in New Zealand rabbit right iliac arteries and the animals were sacrificed after 28 days for histomorphometric analysis. For the assessment of endothelial regrowth in 90 days, 12 rabbits were subjected to PLGA-coated (n = 3), low-dose (n = 3), high-dose (n = 3), and extreme-dose (n = 3) stent implantation. In vitro studies revealed that D-24851 exerts its growth inhibitory effects via inhibition of proliferation and induction of apoptosis without increasing the expression of heat shock protein-70, a cytoprotective and antiapoptotic protein. Treatment with low-dose D-24851 stents was associated with a significant reduction in neointimal area and percentage stenosis only compared with bare metal stents (38% [P = 0.029] and 35% [P = 0.003] reduction, respectively). Suboptimal healing, however, was observed in all groups of D-24851-loaded stents in 90 days in comparison with PLGA-coated stents. We conclude that low-dose D-24851-eluting polymer-coated stents significantly inhibit neointimal hyperplasia at 28 days through inhibition of proliferation and enhancement of apoptosis. In view of the suboptimal re-endothelialization, longer-term studies are needed in order to establish whether the inhibition of intimal growth is maintained.

  12. Antirestenotic Effects of a Novel Polymer-Coated D-24851 Eluting Stent. Experimental Data in a Rabbit Iliac Artery Model

    SciTech Connect

    Lysitsas, Dimitrios N.; Katsouras, Christos S.; Papakostas, John C.; Toumpoulis, Ioannis K.; Angelidis, Charalampos; Bozidis, Petros; Thomas, Christopher G.; Seferiadis, Konstantin; Psychoyios, Nikolaos; Frillingos, Stathis; Pavlidis, Nikolaos; Marinos, Euaggelos; Khaldi, Lubna; Sideris, Dimitris A.; Michalis, Lampros K.

    2007-11-15

    Experimental and clinical data suggest that stents eluting antiproliferative agents can be used for the prevention of in-stent restenosis. Here we investigate in vitro the antiproliferative and apoptotic effect of D-24851 and evaluate the safety and efficacy of D-24851-eluting polymer-coated stents in a rabbit restenosis model (n = 53). Uncoated stents (n = 6), poly (dl-lactide-co-glycolide) (PLGA)-coated stents (n = 7), and PLGA-coated stents loaded with 0.08 {+-} 0.0025 {mu}M (31 {+-} 1 {mu}g; low dose; n = 7), 0.55 {+-} 0.02 {mu}M (216 {+-} 8 {mu}g; high dose; n = 6), and 4.55 {+-} 0.1 {mu}M (1774 {+-} 39 {mu}g; extreme dose; n = 5) of D-24851 were randomly implanted in New Zealand rabbit right iliac arteries and the animals were sacrificed after 28 days for histomorphometric analysis. For the assessment of endothelial regrowth in 90 days, 12 rabbits were subjected to PLGA-coated (n = 3), low-dose (n = 3), high-dose (n = 3), and extreme-dose (n = 3) stent implantation. In vitro studies revealed that D-24851 exerts its growth inhibitory effects via inhibition of proliferation and induction of apoptosis without increasing the expression of heat shock protein-70, a cytoprotective and antiapoptotic protein. Treatment with low-dose D-24851 stents was associated with a significant reduction in neointimal area and percentage stenosis only compared with bare metal stents (38% [P = 0.029] and 35% [P = 0.003] reduction, respectively). Suboptimal healing, however, was observed in all groups of D-24851-loaded stents in 90 days in comparison with PLGA-coated stents. We conclude that low-dose D-24851-eluting polymer-coated stents significantly inhibit neointimal hyperplasia at 28 days through inhibition of proliferation and enhancement of apoptosis. In view of the suboptimal re-endothelialization, longer-term studies are needed in order to establish whether the inhibition of intimal growth is maintained.

  13. Therapeutic Effects of Intra-Articular Ultrapurified Low Endotoxin Alginate Administration on Experimental Osteoarthritis in Rabbits.

    PubMed

    Igarashi, Tatsuya; Iwasaki, Norimasa; Kawamura, Daisuke; Tsukuda, Yukinori; Kasahara, Yasuhiko; Todoh, Masahiro; Tadano, Shigeru; Minami, Akio

    2012-01-01

    We have developed an ultrapurified low endotoxin alginate (UPLE alginate), which can drastically reduce endotoxin levels. Our purposes were to examine the effects of UPLE alginate administration on osteoarthritis (OA) progression and to determine the adequate molecular weight of the UPLE alginate for therapeutic effects. To induce knee OA, 35 Japanese White rabbits underwent anterior cruciate ligament transection. Intra-articular injections of 0.3 mL solution of each material were started at 4 weeks postoperatively for a total of 5 weekly injections. Seventy knees were divided into the following groups: AL430 (430 kDa molecular weight UPLE alginate), AL1000 (1,000 kDa), AL1700 (1,700 kDa), HA (hyaluronan), and NS (normal saline). At 9 weeks postoperatively, all knees were assessed macroscopically, histologically, and mechanically. Macroscopically, the UPLE alginate groups exhibited milder cartilage degradation compared to that of the NS and HA groups. Histological findings of the UPLE alginate groups showed an obvious reduction in the severity of OA. The histological scores of Kikuchi et al. were superior in the alginate treatment groups compared to the NS group. The friction coefficient of the AL1000 group was significantly lower than that of the NS and HA groups. This study indicates that our UPLE alginates, especially AL1000, have promising potential as an effective agent in preventing OA progression.

  14. Therapeutic Effects of Intra-Articular Ultrapurified Low Endotoxin Alginate Administration on Experimental Osteoarthritis in Rabbits

    PubMed Central

    Igarashi, Tatsuya; Kawamura, Daisuke; Tsukuda, Yukinori; Kasahara, Yasuhiko; Todoh, Masahiro; Tadano, Shigeru; Minami, Akio

    2012-01-01

    Objective: We have developed an ultrapurified low endotoxin alginate (UPLE alginate), which can drastically reduce endotoxin levels. Our purposes were to examine the effects of UPLE alginate administration on osteoarthritis (OA) progression and to determine the adequate molecular weight of the UPLE alginate for therapeutic effects. Design: To induce knee OA, 35 Japanese White rabbits underwent anterior cruciate ligament transection. Intra-articular injections of 0.3 mL solution of each material were started at 4 weeks postoperatively for a total of 5 weekly injections. Seventy knees were divided into the following groups: AL430 (430 kDa molecular weight UPLE alginate), AL1000 (1,000 kDa), AL1700 (1,700 kDa), HA (hyaluronan), and NS (normal saline). At 9 weeks postoperatively, all knees were assessed macroscopically, histologically, and mechanically. Results: Macroscopically, the UPLE alginate groups exhibited milder cartilage degradation compared to that of the NS and HA groups. Histological findings of the UPLE alginate groups showed an obvious reduction in the severity of OA. The histological scores of Kikuchi et al. were superior in the alginate treatment groups compared to the NS group. The friction coefficient of the AL1000 group was significantly lower than that of the NS and HA groups. Conclusion: This study indicates that our UPLE alginates, especially AL1000, have promising potential as an effective agent in preventing OA progression. PMID:26069620

  15. Susceptibility of piglets to rabbit hemorrhagic disease virus following experimental infection.

    PubMed Central

    Shien, J H; Lee, L H

    2000-01-01

    The possibility exists that rabbit hemorrhagic disease virus (RHDV) can be transmitted to swine, through lapinized hog cholera virus (HCV) vaccine. To investigate the infectivity of RHDV in swine, 16 four- to six-week-old piglets were inoculated subcutaneously with RHDV, and samples of liver, lung, spleen, kidney, bile, adrenal gland, tonsil, mesenteric lymph node, thymus, urine, buffy coat, and feces were collected from each of 2 animals on Days 0, 1, 2, 3, 5, 7, 14, and 28 post infection. Using reverse transcription-polymerase chain reaction, viral RNA was detected in most tissues by Day 3 and was absent after Day 5, except in lung and liver tissues, in which viral RNA was detected up to Day 14. Viral RNA was not detected in kidney, urine, feces or bile. Antibody responses, as detected by hemagglutination inhibition, were of low titer and short duration, and were similar in animals inoculated with viable RHD and in those given formalin-inactivated RHDV (n = 2). Neither viral RNA nor antibody were detected in the negative control or in the uninfected, in-contact animals. Images Figure 2. PMID:10805254

  16. Detection and neutralization of cobra venom using rabbit antiserum in experimental envenomated mice.

    PubMed

    Venkatesan, C; Sarathi, M; Balasubramanian, G; Saravanan, A; Vimal, S; Madan, N; Majeed, S Abdul; Raj, N Sundar; Hameed, A S Sahul; Babu, V Sarath

    2014-07-01

    A sandwich enzyme-linked immunosorbent assay (ELISA) was developed to detect the venom of Indian cobra (Naja naja naja) in various tissues (brain, heart, lungs, liver, spleen, blood, kidneys, and tissue at the site of injection) of mice after cobra venom injected at different time intervals (0, 2, 4, 6, 8, and 12 h intervals up to 24 h). Whole venom antiserum or individual venom protein antiserum (14, 29, 65, 72, and 99 kDa) could recognize N. n. naja venom by Western blotting and ELISA, and antibody titer was also assayed by ELISA. Antiserum raised against cobra venom in rabbit significantly neutralized the toxicity of venom-injected mice at different time intervals after treatment. The assay could detect N. n. naja venom levels up to 2.5 ng/ml of tissue homogenate, and the venom was detected up to 24 h after venom injection. Venom was detected in brain, heart, lungs, liver, spleen, kidneys, tissue at the bite area, and blood. As observed in mice, tissue at the site of bite area showed the highest concentration of venom and the brain showed the least. Moderate amounts of venoms were found in liver, spleen, kidneys, heart, and lungs. Development of a simple, rapid, and species-specific diagnostic kit based on this ELISA technique useful to clinicians is discussed. © The Author(s) 2014.

  17. The Effect of Irreversible Electroporation on the Femur: Experimental Study in a Rabbit Model

    PubMed Central

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

    2015-01-01

    Irreversible electroporation (IRE) is a novel ablation method that has been tested in humans with lung, prostate, kidney, liver, lymph node and presacral cancers. As a new non-thermal treatment, the use of IRE to ablate tumors in the musculoskeletal system might reduce the incidence of fractures. We aimed to determine the ablation threshold of cortical bone and to evaluate the medium- and long-term healing process and mechanical properties of the femur in a rabbit model post-IRE ablation. The ablation threshold of cortical bone was between 1090 V/cm and 1310 V/cm (120 pulses). IRE-ablated femurs displayed no detectable fracture but did exhibit signs of recovery, including osteoblast regeneration, angiogenesis and bone remodeling. In the ablation area, revascularization appeared at 4 weeks post-IRE. Osteogenic activity peaked 8 weeks post-IRE and remained high at 12 weeks. The mechanical strength decreased briefly 4 weeks post-IRE but returned to normal levels within 8 weeks. Our experiment revealed that IRE ablation preserved the structural integrity of the bone cortex, and the ablated bone was able to regenerate rapidly. IRE may hold unique promise for in situ bone tissue ablation because rapid revascularization and active osteogenesis in the IRE ablation area are possible. PMID:26655843

  18. [The pulmonary hemodynamic changes under experimental myocardial ischemia in rabbits following beta-adrenoreceptors blockade].

    PubMed

    Evlakhov, V I; Poiasov, I Z

    2011-08-01

    In acute experiments in anesthetized rabbits, changes of the pulmonary hemodynamics following myocardial ischemia in the region of the descendent left coronary artery were studied as well as in control animals and after the blockade of beta-adrenoreceptors. The myocardial ischemia decreased the left ventricular myocardial contractility, cardiac output and arterial pressure, decreased the pulmonary artery pressure and flow. Following myocardial ischemia, the pulmonary artery pressure decreased less than pulmonary artery blood flow as the result of elevating of the left atrial pressure, meanwhile pulmonary vascular resistance was not changed. Following myocardial ischemia in animals after the blockade of the beta-adrenoreceptors, the pulmonary flow decreased the same as in control animals. However, the pulmonary artery pressure was decreased twofold more significantly than in control animals, and its diminishing was in the same degree as the pulmonary artery flow. Following myocardial ischemia after the blockade of the beta-adrenoreceptors, the pulmonary vascular resistance decreased whereas the left atrial pressure did not change significantly because the myocardial contractility decreased less than in control animals.

  19. Olfactory route for cerebrospinal fluid drainage into the cervical lymphatic system in a rabbit experimental model☆

    PubMed Central

    Liu, Haisheng; Ni, Zhili; Chen, Yetao; Wang, Dong; Qi, Yan; Zhang, Qiuhang; Wang, Shijie

    2012-01-01

    The present study analyzed the anatomical association between intracranial subarachnoid space and the cervical lymphatic system. X-ray contrast medium and Microfil® (Microfil compounds fill and opacify microvascular and other spaces of non-surviving animals and post-mortem tissue under physiological injection pressure) were injected into the cisterna magna of the rabbit, and perineural routes of cerebrospinal fluid outflow into the lymphatic system were visualized. Under a surgical operating microscope, Microfil was found within the subarachnoid space and along the olfactory nerves. At the nasal mucosa, a lymphatic network was identified near the olfactory nerves, which crossed the nasopharyngeal region and finally emptied into the superficial and deep cervical lymph nodes. Under a light microscope, Microfil was visible around the olfactory nerves and within lymphatic vessels. These results suggested that cerebrospinal fluid drained from the subarachnoid space along the olfactory nerves to nasal lymphatic vessels, which in turn, emptied into the cervical lymph nodes. This anatomical route, therefore, allowed connection between the central nervous system and the lymphatic system. PMID:25737700

  20. Changes in hematological, hemostatic and biochemical parameters induced experimentally in rabbits by Loxosceles gaucho spider venom.

    PubMed

    Tavares, Flávio Luiz; Sousa-e-Silva, Maria Cristina Cirillo; Santoro, Marcelo Larami; Barbaro, Kátia Cristina; Rebecchi, Ivanise Marina Moretti; Sano-Martins, Ida Sigueko

    2004-10-01

    Human accidents caused by Loxosceles spiders may result in local dermal necrosis and, in some cases, severe systemic reactions - such as intravascular hemolysis, disseminated intravascular coagulation (DIC), renal failure and death. Since many aspects of envenomation by Loxosceles spiders remain unclear, we studied the hematological and hemostatic responses induced by the i.d. injection of 10 microg/kg Loxosceles gaucho venom in rabbits. For this purpose, total blood cell count, platelet function, coagulation tests and biochemical parameters were analysed at 3, 24, 48, 72 and 120 hours after venom administration. Thrombocytopenia and leukopenia were noted at 3 and 24 hours. Histopathological analysis of the skin lesion, performed at 24 hours after venom administration, showed a massive presence of leukocytes and platelets, hemorrhage and thrombus formation at the injection site. At 72 and 120 hours, neutrophilic leukocytosis and thrombocytosis were observed. Platelet hyperaggregation was noticeable at 48 and 72 hours. Haptoglobin and fibrinogen levels were elevated early and remained in high levels over time. Significant increases in coagulation factors V, VII, VIII, IX, X and XI were noted at 120 hours. The results showed that neither intravascular hemolysis nor DIC occurred. However, the early onset of thrombocytopenia and leukopenia are important findings that may be related to dermal necrosis formation during loxoscelism.

  1. [Differential circulatory value of various femoral shaft areas--experimental studies in rabbits].

    PubMed

    Nutz, V

    1988-01-01

    15 rabbits underwent osteotomia of the left femur including lesion of the medullary vessels, 5 times in the proximal, 5 times in the middle, 5 times in the distal diaphysis. Changes in blood flow before and after osteotomia were measured by the "tracer microspheres" -method in the proximal, middle, and distal diaphysis of the femur and the tibia, in the marrow of femur and tibia, in the m. rectus femoris, and the m. tibialis anterior. After lesion of the femur diaphysis a significant reduction of blood flow was found in all tissues of the left leg which must have been caused by arterial spasm. In the diaphysis and marrow of femur, however, the reduction of blood flow was even greater and showed a characteristic pattern concerning the lesion of the medullary vessels. Osteotomia in the proximal diaphysis led to a greater reduction of blood flow in diaphysis and marrow than osteotomia in the middle and distal diaphysis did. The alteration of the diaphysis blood flow is different in the proximal, middle, and distal part in all cases of osteotomia. The characteristic pattern of diaphysis blood flow alteration by osteotomia can be explained by topography of the femur vessels. Their relations to clinical observations are discussed.

  2. Proteomic analysis of rabbit tear fluid: Defensin levels after an experimental corneal wound are correlated to wound closure.

    PubMed

    Zhou, Lei; Beuerman, Roger W; Huang, Liqun; Barathi, Amutha; Foo, Yong Hwee; Li, Sam F Y; Chew, Fook Tim; Tan, Donald

    2007-09-01

    The cornea is the major refracting optical element of the eye and therefore critical for forming a retinal image. The exposed surface of the eye is protected from pathogens by the innate immune system whose components include defensins, naturally occurring peptides with antimicrobial properties, and the physical barrier formed by the outer epithelial layer of the cornea. The proteomic approach has revealed that tear levels of defensins are correlated with the course of healing of an experimental corneal wound. Tears were collected from New Zealand White rabbits prior to (day 0) and daily for 5 days (days 1-5) following a standard unilateral 6 mm diameter corneal epithelial abrasion. Tear protein profiles obtained from wounded and contra-lateral control eyes were compared using SELDI ProteinChip technology. Peptides and proteins of interest were purified by RP-HPLC and characterized by nanoESI-MS/MS. Mass spectra of tears on post-wound day 1, revealed 13 peaks whose level decreased and five that increased. During wound healing the tear protein profile correlated with wound closure. An important finding was that the levels of rabbit defensins (NP-1 and NP-2), which were elevated after wounding returned to normal levels by the time the corneal abrasion healed. Relative quantification of NP-2 in tear fluid prior to (day 0) and after corneal wounding (days 1- 3) was determined using iTRAQ technology. A corneal wound eliminates the barrier function of innate immunity and puts the cornea at risk from microbial attack until the epithelial cells restore the surface barrier. The increased availability of defensins in the tears during healing suggests that these peptides could protect the cornea from microbial attack during a period of increased vulnerability.

  3. Evaluation of viscoelastic poly(ethylene glycol) sols as vitreous substitutes in an experimental vitrectomy model in rabbits

    PubMed Central

    Pritchard, Christopher D.; Crafoord, Sven; Andréasson, Sten; Arnér, Karin M.; O’Shea, Timothy M.; Langer, Robert; Ghosh, Fredrik K.

    2014-01-01

    The aim of this study was to employ an experimental protocol for in vivo evaluation of sols of 5 wt.% poly(ethylene glycol) (PEG) in phosphate-buffered saline as artificial vitreous substitutes. A 20 gauge pars plana vitrectomy and posterior vitreous detachment were performed in the right eye of eight pigmented rabbits. Approximately 1 ml of the viscoelastic PEG sols was then injected into the vitreous space of six eyes. PEG with an average molecular weight of 300,000 and 400,000 g mol−1 was used in two and four eyes, respectively. Two eyes received balanced salt solution and served as controls. Full-field electroretinography was carried out and intra-ocular pressure (IOP, palpation) measured pre- and post-operatively at regular intervals up to 41 days. The rabbits were killed and the eyes examined by retinal photography, gross macroscopic examination and histology. The viscoelastic sols were successfully injected and remained translucent throughout the post-operative period, with some inferior formation of precipitates. None of the eyes displayed IOP elevation post-operatively, but in three of the PEG sol injected eyes transient hypotony was noted. One eye sustained retinal detachment during surgery and another two in the post-operative period. ERG recordings confirmed preservation of retinal function in three out of four eyes injected with 400,000 g mol−1 PEG. Histological examination revealed up-regulation of glial acidic fibrillary protein in Müller cells in PEG sol injected eyes, but normal overall morphology in eyes with attached retinas. The viscosity of the sol was not retained throughout the post-operative period, indicating the demand for polymer cross-linking to increase residence time. The results provide promising preliminary results on the use of PEG hydrogels as a vitreous substitute. PMID:21081184

  4. Evaluation of viscoelastic poly(ethylene glycol) sols as vitreous substitutes in an experimental vitrectomy model in rabbits.

    PubMed

    Pritchard, Christopher D; Crafoord, Sven; Andréasson, Sten; Arnér, Karin M; O'Shea, Timothy M; Langer, Robert; Ghosh, Fredrik K

    2011-03-01

    The aim of this study was to employ an experimental protocol for in vivo evaluation of sols of 5 wt.% poly(ethylene glycol) (PEG) in phosphate-buffered saline as artificial vitreous substitutes. A 20 gauge pars plana vitrectomy and posterior vitreous detachment were performed in the right eye of eight pigmented rabbits. Approximately 1 ml of the viscoelastic PEG sols was then injected into the vitreous space of six eyes. PEG with an average molecular weight of 300,000 and 400,000 g mol(-1) was used in two and four eyes, respectively. Two eyes received balanced salt solution and served as controls. Full-field electroretinography was carried out and intra-ocular pressure (IOP, palpation) measured pre- and post-operatively at regular intervals up to 41 days. The rabbits were killed and the eyes examined by retinal photography, gross macroscopic examination and histology. The viscoelastic sols were successfully injected and remained translucent throughout the post-operative period, with some inferior formation of precipitates. None of the eyes displayed IOP elevation post-operatively, but in three of the PEG sol injected eyes transient hypotony was noted. One eye sustained retinal detachment during surgery and another two in the post-operative period. ERG recordings confirmed preservation of retinal function in three out of four eyes injected with 400,000 g mol(-1) PEG. Histological examination revealed up-regulation of glial acidic fibrillary protein in Müller cells in PEG sol injected eyes, but normal overall morphology in eyes with attached retinas. The viscosity of the sol was not retained throughout the post-operative period, indicating the demand for polymer cross-linking to increase residence time. The results provide promising preliminary results on the use of PEG hydrogels as a vitreous substitute. Copyright © 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  5. Intravascular photoacoustic imaging of exogenously labeled atherosclerotic plaque through luminal blood

    NASA Astrophysics Data System (ADS)

    Yeager, Doug; Karpiouk, Andrei; Wang, Bo; Amirian, James; Sokolov, Konstantin; Smalling, Richard; Emelianov, Stanislav

    2012-10-01

    Combined intravascular ultrasound and intravascular photoacoustic (IVUS/IVPA) imaging has been previously established as a viable means for assessing atherosclerotic plaque morphological and compositional characteristics using both endogenous and exogenous contrast. In this study, IVUS/IVPA imaging of atherosclerotic rabbit aortas following systemic injection of gold nanorods (AUNRs) with peak absorbance within the tissue optical window is performed. Ex vivo imaging results reveal a high photoacoustic signal from localized AUNRs in regions with atherosclerotic plaques. Corresponding histological staining further confirms the preferential extravasation of AUNRs in atherosclerotic regions with compromised luminal endothelium and acute inflammation. The ability to detect AUNRs using combined IVUS and photoacoustic imaging in the presence of luminal saline and luminal blood is evaluated using both spectroscopic and single wavelength IVPA imaging techniques. Results demonstrate that AUNR detection within the arterial wall can be achieved using both methods, even in the case of imaging through luminal blood.

  6. Experimental implantation and long-term testing of an intraocular vision aid in rabbits.

    PubMed

    Szurman, Peter; Warga, Max; Roters, Sigrid; Grisanti, Salvatore; Heimann, Uta; Aisenbrey, Sabine; Rohrbach, Jens M; Sellhaus, Bernd; Ziemssen, Focke; Bartz-Schmidt, Karl U

    2005-07-01

    To develop an intraocular vision aid to provide artificial vision in severely traumatized eyes, where neuroretinal function could be preserved but irreversible anterior segment opacification resulted in blindness. The basis of an intraocular vision aid is in principle a telemetric circuit to bridge the opaque cornea and to allow for artificial light stimulation of the retina. The visual prosthesis comprises an external high-dynamic range complementary metal oxide semiconductor camera and digital signal processing unit and an intraocular miniaturized light-emitting diode array to project the image onto the retina. For in vivo testing of long-term function and biocompatibility, silicone-encapsulated active photodiodes were implanted in 13 pigmented rabbits and were followed up for up to 21 months. Lens extraction and stable fixation of the device in the ciliary sulcus were successful in all cases. For up to 21 months inductive energy transmission and wireless stimulation of the implants could be maintained. Electrophysiologic data and histology demonstrated a good tissue biocompatibility in the long-term follow-up. The results demonstrate the general feasibility and biocompatibility to implant and fixate an intraocular light-emitting diode prosthesis. Inductive energy transmission to the intraocular device and wireless light stimulation are assured in the long term but depend on meticulous water-impermeable encapsulation of the delicate microelectronic components. Clinical Relevance An intraocular vision aid compound system with a high-resolution light-emitting diode matrix might be a future treatment option to restore vision in blind eyes with severe anterior segment disorders.

  7. Experimental femtosecond laser photodisruption of rabbit sclera for minimally invasive laser sclerostomy: An in vitro study

    NASA Astrophysics Data System (ADS)

    Yang, Xiaobo; Dai, Nengli; Long, Hua; Lu, Peixiang; Li, Wan; Jiang, Fagang

    2010-07-01

    Femtosecond laser technology, used as a minimally invasive tool in intrastromal refractive surgery, may also have potential as a useful instrument for glaucoma filtration surgery. The purpose of the present study was to evaluate the feasibility of minimally invasive laser sclerostomy by femtosecond laser photodisruption and seek the appropriate patterns of laser ablation and relevant laser parameters. A femtosecond laser (800 nm/50 fs/1 kHz), focused by a 0.1 numerical aperture (NA) objective lens, with different pulse energies and exposure times was applied to ablate hydrated rabbit sclera in vitro. The irradiated samples were examined by scanning electron microscopy (SEM). By moving a three-dimensional, computer-controlled translation stage to which the sample was attached, the femtosecond laser could produce three types of ablation patterns, including linear ablation, cylindrical aperture and rectangular cavity. With pulse energies ranging from 37.5 to 150 μJ, the linear lesions were consistently observed at the inner surface of sclera, whereas it failed to make any photodisruption if pulse energy was below the threshold value of 31.25 μJ, with the corresponding threshold intensity of 4.06×10 14 W/cm 2. The depths of the linear lesions increased linearly with both pulse energy (37.5-150 μJ) and exposure time (0.1-0.4 s). Histological examination showed the incisions produced by femtosecond laser photodisruption had precise geometry and the edges were sharp and smooth, with no evidence of collateral damage to the surrounding tissue. Our results predict the potential application of femtosecond laser pulses in minimally invasive laser sclerostomy for glaucoma treatment.

  8. Responses of noradrenergic nerves in rabbit ear-artery before and after experimental frost-bite.

    PubMed

    Aas, P

    1994-04-01

    Experiments were designed to determine the effects of sub-zero temperatures on the function of the noradrenergic innervation of a peripheral blood-vessel. The central ear-artery of the rabbit was used for this purpose. The ear was exposed to temperatures of -6, -9 or -18 degrees C in vivo for 15 min. After 1 day (24 h) or 6 days in vivo, the central ear-artery was dissected free, incubated in [3H]-noradrenaline (NA) and stimulated in vitro with high potassium (75 mM) for 5 min to evoke release of [3H]-NA. The release of [3H]-NA was Ca(2+)-dependent. One day after exposure to -6, -9 or -18 degrees C, increases of 45-57 and 44-72% and a reduction of 12-35% were observed, respectively, in three successive potassium-evoked NA-releases. After 6 days in vivo an increase of 30-34% was observed following exposure to -6 degrees C, while no alteration was observed after exposure to -9 degrees C. A reduction of 84-89% was recorded after exposure to -18 degrees C. Following this exposure to -18 degrees C, there was also a great reduction in the evoked release of [3H]-NA compared with the spontaneous release, whereas this correlation did not change after exposure to -6 and -9 degrees C. The total uptake of [3H]-NA was unchanged after freezing the tissue at -6 degrees C, but was substantially reduced after exposure to -9 and -18 degrees C. A short period of in vivo restoration (6 days, enhanced the uptake of [3H]-NA.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Influence of initial implant mobility on the integration of titanium implants. An experimental study in rabbits.

    PubMed

    Ivanoff, C J; Sennerby, L; Lekholm, U

    1996-06-01

    In the present study, the influence of initial instability on the healing of titanium implants was studied in 9 lop-eared rabbits. Titanium implants (Brånemark System) were inserted in the tibiae, a location with cortical bone only, in such a way that they were either stable (control), rotation-mobile, or totally mobile. Implants were also inserted in the distal femoral condyles, representing an implantation bed with mainly cancellous bone, so they either showed no initial mobility (control) or were rotation-mobile. After 12 weeks of healing, the implants were retrieved, together with surrounding bone, fixed, dehydrated, and embedded in plastic resin. About 10 micron thick ground sections were prepared for light microscopic morphometry. The mineralized bone to titanium contact, and the amount of bone occupying the threads, were calculated, whereafter the outcome of the different locations were compared. All retrieved implants were clinically stable at the of the experiment. For the tibia sites, a statistically significant less bone to titanium contact, and a less amount of bone in the threads, were found for the totally mobile implants, as compared to the corresponding initially stable controls. Moreover, a statistically significant higher amount of bone was found in the threads of the rotation-mobile implants inserted in the femoral condyle as compared to their initially stable controls. The study indicated that initial rotation-mobility, independent if it occurs in cortical or trabecular bone, does not necessarily lead to an inferior integration of unloaded implants. However, initial total implant mobility within the cortical layer results in a statistically significant less amount of bone around the implants, as compared to stable controls.

  10. Nuclear microscopy of atherosclerotic tissue: A review

    NASA Astrophysics Data System (ADS)

    Watt, Frank; Ren, M. Q.; Xie, J. P.; Tan, B. K. H.; Halliwell, B.

    2001-07-01

    This paper reviews the work carried out in the Research Centre for Nuclear Microscopy, NUS on the role of iron in coronary heart disease, using the technique of nuclear microscopy to determine the levels of iron and other trace elements in the artery wall and lesions. These investigations have indicated that iron may play a significant role in the development of atherosclerosis, probably through the promotion of cytotoxic free radicals leading to the oxidation of low-density lipoprotein (LDL). Using a rabbit model we have observed that early atherosclerotic lesions, induced by feeding the animals on a 1% cholesterol diet, contain increased levels of iron (up to 8 times) compared with the adjacent healthy artery wall. In a follow-up time sequence study, we have shown that iron accumulation occurs at the onset of lesion formation, which takes place around 4-6 weeks after exposure to the 1% cholesterol diet. As the lesions mature, they enlarge to occupy a significant fraction of the artery wall, and at about 16 weeks the lesions begin to show signs of calcification. In an additional experiment, where the cholesterol fed rabbits were kept anaemic through weekly bleeding, the iron content of the artery wall was reduced and the onset of atherogenesis was delayed. In a further investigation, rabbits were fed on a 1% cholesterol diet and after 6 weeks (corresponding to the period of early lesion formation) a test group was subjected to treatment using the iron chelator desferal. Preliminary results indicate that during the treatment with desferal, lesion development was slowed down.

  11. Image segmentation applied to atherosclerotic lesion

    NASA Astrophysics Data System (ADS)

    Morales, R. Rodríguez; Martínez, T. E. Alarcón; Cuello, L. Sánchez; Fernández-Britto, J. E.; Taylor, Charles

    2000-10-01

    The results obtained using two techniques: a supervised method and other unsupervised for image segmentation of atherosclerotic lesions of the thoracic aorta, are presented. Segmentation was used both with and without pre-processing. In this paper, the advantages of pre-processing prior to are shown for discriminating among the different atherosclerotic lesions (fatty streaks, fibrous plaque, complicated plaques and calcified plaques) and identifying them. The results using a supervised method were poor when searching vector consisted of two components, the mean and the variance. This digital image processing was done in order to use the automated atherometric system. This methodology has been considered to be suitable for the characterization of the atherosclerotic lesions in any artery and its organ-related damage in any vascular sector or group of patients. Final results were compared with manual segmentation realized by an expert, where difference errors less than 3% were observed. It is demonstrated by extensive experimentation, using real image data, that proposed strategy is fast and robust in the environment of a personal computer.

  12. INFECTIOUS PAPILLOMATOSIS OF RABBITS

    PubMed Central

    Shope, Richard E.; Hurst, E. Weston

    1933-01-01

    A papilloma has been observed in wild cottontail rabbits and has been found to be transmissible to both wild and domestic rabbits. The clinical and pathological pictures of the condition have been described. It has been found that the causative agent is readily filtrable through Berkefeld but not regularly through Seitz filters, that it stores well in glycerol, that it is still active after heating to 67°C. for 30 minutes, but not after heating to 70°C., and that it exhibits a marked tropism for cutaneous epithelium. The activities and properties of the papilloma-producing agent warrant its classification as a filtrable virus. Rabbits carrying experimentally produced papillomata are partially or completely immune to reinfection and, furthermore, their sera partially or completely neutralize the causative virus. The disease is transmissible in series through wild rabbits and virus of wild rabbit origin is readily transmissible to domestic rabbits, producing in this species papillomata identical in appearance with those found in wild rabbits. However, the condition is not transmissible in series through domestic rabbits. The possible significance of this observation has been discussed. The virus of infectious papillomatosis is not related immunologically to either the virus of infectious fibroma or to that of infectious myxoma of rabbits. PMID:19870219

  13. Pet rabbits.

    PubMed

    Hillyer, E V

    1994-01-01

    Pet rabbits are becoming more common, and rabbit owners are demanding quality veterinary care. This article provides a broad overview of pet rabbit medicine, which is a relatively new field compared to laboratory and farm rabbit medicine. The most common differential diagnoses for presenting complaints are summarized in table form. Disease conditions are reviewed individually in the text. Sources of further information on veterinary care of rabbits are listed throughout the text, in an appendix, and in the references.

  14. Evaluation of atherosclerotic lesions using dextran- and mannan–dextran-coated USPIO: MRI analysis and pathological findings

    PubMed Central

    Tsuchiya, Keiko; Nitta, Norihisa; Sonoda, Akinaga; Nitta-Seko, Ayumi; Ohta, Shinichi; Takahashi, Masashi; Murata, Kiyoshi; Mukaisho, Kenichi; Shiomi, Masashi; Tabata, Yasuhiko; Nohara, Satoshi

    2012-01-01

    Magnetic resonance imaging (MRI) can detect atherosclerotic lesions containing accumulations of ultrasmall superparamagnetic iron oxides (USPIO). Positing that improved USPIO with a higher affinity for atherosclerotic plaques would yield better plaque images, we performed MRI and histologic studies to compare the uptake of dextran- and mannan–dextran-coated USPIO (D-USPIO and DM-USPIO, respectively) by the atherosclerotic walls of rabbits. We intravenously injected atherosclerotic rabbits with DM-USPIO (n = 5) or D-USPIO (n = 5). Two rabbits were the controls. The doses delivered were 0.08 (dose 1) (n = 1), 0.4 (dose 2) (n = 1), or 0.8 (dose 3) (n = 3) mmol iron/Kg. The dose 3 rabbits underwent in vivo contrast-enhanced magnetic resonance angiography (MRA) before and 5 days after USPIO administration. Afterwards, all animals were euthanized, the aortae were removed and subjected to in vitro MRI study. The signal-to-noise ratio (SNR) of the aortic wall in the same region of interest (ROI) was calculated in both in vivo and in vitro studies. Histological assessment through measurement of iron-positive regions in Prussian blue-stained specimens showed that iron-positive regions were significantly larger in rabbits injected with DM- rather than D-USPIO (P < 0.05) for all doses. In vivo MRA showed that the SNR-reducing effect of DM- was greater than that of D-USPIO (P < 0.05). With in vitro MRI scans, SNR was significantly lower in rabbits treated with dose 2 of DM-USPIO compared with D-USPIO treatment (P < 0.05), and it tended to be lower at dose 3 (P < 0.1). In conclusion, we suggest that DM-USPIO is superior to D-USPIO for the study of atherosclerotic lesions in rabbits. PMID:22619561

  15. Application of infrared fiber optic imaging in atherosclerotic plaques

    NASA Astrophysics Data System (ADS)

    Guo, Bujin; Casscells, S. W.; Bearman, Gregory H.; McNatt, Janice; Naghevi, Morteza; Malik, Basit A.; Gul, Khawar; Willerson, James T.

    1999-07-01

    Rupture of atherosclerotic plaques - the main cause of heart attach and stokes - is not predictable. Hence even treadmill stress tests fail to detect many persons at risk. Fatal plaques are found at autopsies to be associated with active inflammatory cells. Classically, inflammation is detected by its swelling, red color, pain and heat. We have found that heat accurately locates the dangerous plaques that are significantly warmer then atherosclerotic plaques without the same inflammation. In order to develop a non-surgical method of locating these plaques, an IR fiber optic imaging system has been developed in our laboratory to evalute the causes and effect of heat in atherosclerotic plaques. The fiber optical imagin bundle consists of 900 individual As2S3 chalcogenide glass fibers which transmit IR radiation from 0.7 micrometers 7 micrometers with little energy loss. By combining that with a highly sensitive Indium Antimonide IR focal plane array detector, we are able to obtain thermal graphic images in situ. The temperature heterogeneity of atherosclerotic plaques developed in the arteral of the experimental animal models is under study with the new device. The preliminary experimental results from the animal model are encouraging. The potential of using this new technology in diagnostic evaluation of the vulnerable atherosclerotic plaques is considerable.

  16. Vigna unguiculata modulates cholesterol induced cardiac markers, genotoxicity and gene expressions profile in an experimental rabbit model.

    PubMed

    Janeesh, P A; Abraham, Annie

    2013-04-25

    Vigna unguiculata (VU) leaves are edible and used as a leafy vegetable in cuisine from traditional times in India. This study was designed to investigate the cardioprotective effect of VU in cholesterol fed rabbits. The animals were randomly divided into 4 groups of 6 animals each and the experimental period was 3 months. Group I-ND [normal diet 40 g feed], Group II-ND + FVU [flavanoid fraction of Vigna unguiculata (150 mg kg (-1) per body weight)], Group III-ND + CH [cholesterol (400 mg)] and Group IV-ND + CH (400 mg) +FVU (150 mg kg(-1) per body weight). After the experimental period, animals were sacrificed and the various parameters, such as cardiac markers, toxicity parameters, genotoxicity and gene expression, were investigated. Cholesterol feeding causes a significant increase in the levels of cardiac marker enzymes, namely lactate dehydrogenase (LDH) and creatine phospokinase (CPK), atherogenic index, toxicity parameters like serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) were elevated. Antioxidant enzyme levels were decreased, lipid peroxidation products in heart tissue and inflammatory markers, namely cyclooxygenase (COX2) and lipooxygenase (LOX15) in peripheral blood monocytes (PBMCs), were significantly increased. A genotoxicity study using a Comet assay and gene expression by reverse transcriptase-polymerase chain reaction (RT-PCR) of transforming growth factor-b1 (TGF-b1) and heme oxygenase-1 (HO-1) from heart tissue showed an altered expression in the disease group. The supplementation of the flavonoid fraction of Vigna unguiculata leaves (FVU) in the CH + FVU group caused the reversal of the above parameters and cardiotoxicity to near normal when compared with the CH group and FVU. This study revealed the cardioprotective nature of Vigna unguiculata in preventing cardiovascular diseases and this effect is attributed to the presence of antioxidants and the antihyperlipidemic properties of the

  17. Atherosclerotic Oxalosis in Coronary Arteries

    PubMed Central

    Fishbein, Gregory A.; Micheletti, Robert G.; Currier, Judith S.; Singer, Elyse; Fishbein, Michael C.

    2008-01-01

    Summary There are many forms of oxalosis, with deposition of oxalate crystals in various organs, including arteries. In this retrospective study we describe deposition of calcium oxalate crystals within atherosclerotic plaques in coronary arteries of 4 patients, a site of oxalate deposition not previously reported. We suggest the phrase “atherosclerotic oxalosis” for this finding. Background Systemic oxalosis may be hereditary or acquired. In these cases, calcium oxalate deposits have been reported in numerous tissues, including the media of arteries. In any category, calcium oxalate deposition has not been described within atherosclerotic plaques in any arteries. Methods As part of a retrospective clinicopathologic study, 80 hearts were obtained from the National Neurologic AIDS Bank in an effort to study coronary atherosclerosis in patients infected with HIV. The population consisted of 66 HIV-positive and 14 HIV-negative patients with an average age of 47 years; 79% were males. Proximal coronary arteries were serially-sectioned and processed routinely. Sections were studied by H&E staining, and in selected cases, von Kossa stain, and alizarin red S under different conditions, including polarized light, to allow distinction of calcium phosphate from calcium oxalate. Medical histories, autopsy reports, and general autopsy slides were reviewed. Results In 4 patients (3 with AIDS) calcium oxalate crystals were observed within atherosclerotic plaques in the coronary arteries. Similar deposits were seen in the thyroid gland and other organs, but not in the kidneys. None of the patients had chronic renal failure. Conclusion The calcium oxalate crystal deposits observed in the atherosclerotic plaques in coronary arteries of these 4 patients are unique in two ways: 1) these deposits have not previously been described in atherosclerotic plaques, 2) the patients did not demonstrate any of the recognized patterns of oxalosis. We suggest the phrase “atherosclerotic

  18. Autoantibody Production in Rabbits

    PubMed Central

    Asherson, G. L.; Rose, M. Elaine

    1963-01-01

    The finding that the serum of apparently healthy rabbits fixed complement with rabbit liver and kidney has been confirmed. Experimental infection of rabbits with Eimeria stiedae, the cause of hepatic coccidiosis, led to a rise in the titre of serum complement-fixing factors. The rise was statistically significant 14, 21 and 28 days after infection. The factors were regarded as antibodies because they behaved as macroglobulins on diethylaminoethyl—cellulose chromatography and sucrose gradient centrifugation, and as autoantibodies because they fixed complement with the kidney of the rabbits in which they occurred. The antibody reacted with widely distributed antigen(s) with high activity in brain and low activity in skeletal muscle. The possibility that coccidial infection may be responsible for the natural autoantibody of rabbits is discussed. PMID:13965167

  19. STUDIES IN EXPERIMENTAL SYPHILIS : III. FURTHER OBSERVATIONS ON THE POSSIBILITY OF CURE OF SYPHILIS IN THE RABBIT WITH ARSPHENAMINE.

    PubMed

    Chesney, A M; Kemp, J E

    1925-06-30

    Syphilitic rabbits can be treated with arsphenamine in such a manner as to render the lymph nodes incapable of transmitting the infection to normal rabbits. This can be accomplished if treatment is begun either early or comparatively late in the course of the disease. If treatment is begun early, the animals are almost uniformly susceptible to a second infection, whereas, if it is begun late, they are almost uniformly refractory to a second infection. It is suggested that this refractory state in rabbits may be explained by the existence of an acquired immunity which persists after the abolition of the disease, rather than to the persistence of the first infection. It would appear that it is possible under certain conditions to reinoculate rabbits and produce generalized infection without producing any lesion at the portal of entry.

  20. Nonalcoholic steatohepatitis as a novel player in metabolic syndrome-induced erectile dysfunction: an experimental study in the rabbit.

    PubMed

    Vignozzi, Linda; Filippi, Sandra; Comeglio, Paolo; Cellai, Ilaria; Sarchielli, Erica; Morelli, Annamaria; Rastrelli, Giulia; Maneschi, Elena; Galli, Andrea; Vannelli, Gabriella Barbara; Saad, Farid; Mannucci, Edoardo; Adorini, Luciano; Maggi, Mario

    2014-03-25

    A pathogenic link between erectile dysfunction (ED) and metabolic syndrome (MetS) is now well established. Nonalcoholic steatohepatitis (NASH), the hepatic hallmark of MetS, is regarded as an active player in the pathogenesis of MetS-associated cardiovascular disease (CVD). This study was aimed at evaluating the relationship between MetS-induced NASH and penile dysfunction. We used a non-genomic, high fat diet (HFD)-induced, rabbit model of MetS, and treated HFD rabbits with testosterone (T), with the selective farnesoid X receptor (FXR) agonist obeticholic acid (OCA), or with the anti-TNFα mAb infliximab. Rabbits fed a regular diet were used as controls. Liver histomorphological and gene expression analysis demonstrated NASH in HFD rabbits. Several genes related to inflammation (including TNFα), activation of stellate cells, fibrosis, and lipid metabolism parameters were negatively associated to maximal acetylcholine (Ach)-induced relaxation in penis. When all these putative liver determinants of penile Ach responsiveness were tested as covariates in a multivariate model, only the association between hepatic TNFα expression and Ach response was confirmed. Accordingly, circulating levels of TNFα were increased 15-fold in HFD rabbits. T and OCA dosing in HFD rabbits both reduced TNFα liver expression and plasma levels, with a parallel increase of penile eNOS expression and responsiveness to Ach. Also neutralization of TNFα with infliximab treatment fully normalized HFD-induced hypo-responsiveness to Ach, as well as responsiveness to vardenafil, a phosphodiesterase type 5 inhibitor. Thus, MetS-induced NASH in HFD rabbits plays an active role in the pathogenesis of ED, likely through TNFα, as indicated by treatments reducing liver and circulating TNFα levels (T or OCA), or neutralizing TNFα action (infliximab), which significantly improve penile responsiveness to Ach in HFD rabbits.

  1. Structural and biomechanical alterations in rabbit thoracic aortas are associated with the progression of atherosclerosis

    PubMed Central

    2011-01-01

    Background Atherosclerosis is a diffuse and highly variable disease of arteries that alters the mechanical properties of the vessel wall through highly variable changes in its cellular composition and histological structure. We have analyzed the effects of acute atherosclerotic changes on the mechanical properties of the descending thoracic aorta of rabbits fed a 4% cholesterol diet. Methods Two groups of eight male New Zealand White rabbits were randomly selected and fed for 8 weeks either an atherogenic diet (4% cholesterol plus regular rabbit chow), or regular chow. Animals were sacrificed after 8 weeks, and the descending thoracic aortas were excised for pressure-diameter tests and histological evaluation to examine the relationship between aortic elastic properties and atherosclerotic lesions. Results All rabbits fed the high-cholesterol diet developed either intermediate or advanced atherosclerotic lesions, particularly American Heart Association-type III and IV, which were fatty and contained abundant lipid-filled foam cells (RAM 11-positive cells) and fewer SMCs with solid-like actin staining (HHF-35-positive cells). In contrast, rabbits fed a normal diet had no visible atherosclerotic changes. The atherosclerotic lesions correlated with a statistically significant decrease in mean vessel wall stiffness in the cholesterol-fed rabbits (51.52 ± 8.76 kPa) compared to the control animals (68.98 ± 11.98 kPa), especially in rabbits with more progressive disease. Conclusions Notably, stiffness appears to decrease with the progression of atherosclerosis after the 8-week period. PMID:21791107

  2. Atherosclerotic oxalosis in coronary arteries.

    PubMed

    Fishbein, Gregory A; Micheletti, Robert G; Currier, Judith S; Singer, Elyse; Fishbein, Michael C

    2008-01-01

    Systemic oxalosis may be hereditary or acquired. In these cases, calcium oxalate deposits have been reported in numerous tissues, including the media of arteries. In any category, calcium oxalate deposition has not been described within atherosclerotic plaques in any arteries. As part of a retrospective clinicopathologic study, 80 hearts were obtained from the National Neurological AIDS Bank in an effort to study coronary atherosclerosis in patients infected with HIV. The population consisted of 66 HIV-positive and 14 HIV-negative patients with an average age of 47 years; 79% were males. Proximal coronary arteries were serially sectioned and processed routinely. Sections were studied by hematoxylin and eosin staining and, in selected cases, von Kossa stain and alizarin red S under different conditions, including polarized light, to allow distinction of calcium phosphate from calcium oxalate. Medical histories, autopsy reports, and general autopsy slides were reviewed. In four patients (three with AIDS), calcium oxalate crystals were observed within atherosclerotic plaques in the coronary arteries. Similar deposits were seen in the thyroid gland and other organs but not in the kidneys. None of the patients had chronic renal failure. The calcium oxalate crystal deposits observed in the atherosclerotic plaques in the coronary arteries of these four patients are unique in two ways: (a) these deposits have not previously been described in atherosclerotic plaques; (b) the patients did not demonstrate any of the recognized patterns of oxalosis. We suggest the phrase "atherosclerotic oxalosis" to describe this finding.

  3. Protective effect of exercise and alpha tocopherol on atherosclerosis promotion in hypercholesterolemic domestic rabbits

    NASA Astrophysics Data System (ADS)

    Shekh, Mudhir S.; Mahmud, Almas M. R.

    2017-09-01

    This study was designed to determine effects of exercise training (Moderate and severe) and alpha tocopherol on lipid profiles and organ weights in hypercholesterolemic domestic rabbits. Hypercholesterolemia (HC) and atherosclerotic lesions were induced by feeding the male rabbits the standard chow supplemented with 1% cholesterol (atherogenic diet) for 36 days. Experimental rabbits were divided into seven groups: normal (T1), HC control (T2), HC plus alpha tocopherol (0.5mg /animal/day) (T3), HC plus moderate exercise 40 minutes/day (0.5km/day) 5 days/week (T4), HC plus severe exercise 40 minutes/day (1km/day) 5 days/week (T5), HC plus alpha tocopherol plus moderate exercise (T6) and HC plus alpha tocopherol plus severe exercise (T7). After the treatment period of 36th day, blood samples were collected and total cholesterol (TC), Triglyceride (TG), Very low-density lipoprotein (VLDL)-cholesterol, High-density lipoproteins (HDL)-cholesterol, Low-density lipoprotein (LDL)-cholesterol, serum glucose, body and organ weights were assayed and compared with hypercholesterolemic control. Combination of moderate exercise with alpha tocopherol produced significant reduction (P<0.01) in TG and high significant decrement (P<0.001), in VLDL-cholesterol, TC and LDL-cholesterol compared with hypercholesterolemic rabbits. Serum TC, LDL and VLDL (P<0.001) and TG (P<0.01) significantly increased when compared with normal rabbits diet, while, HDL decreased (P<0.05) significantly. Severe exercise group showed no significant change in all lipid profiles. However, the decrement in the above parameters was comparable with hypercholesterolemic rabbits in combination of severe exercise with alpha tocopherol. The results suggest that the combination of moderate exercise with alpha tocopherol can be exploited for prevention of atherosclerosis in hypercholesterolemic rabbits.

  4. Antitoxic immunity in experimental cholera: protection, and serum and local antibody responses in rabbits after enteral and parenteral immunization.

    PubMed Central

    Holmgren, J; Svennerholm, A M; Ouchterlony, O; Anderson, A; Walletström, G; Westerberg-Berndtsson, U

    1975-01-01

    The protective effect of enternal and parenteral immunization with cholera toxin antigen against experimental cholera in rabbits was studied by using the small-bowel loop technique. Subcutaneous injection of crude toxin as well as purified toxin or toxoids gave rise to significant protection against toxin challenge. The enhanced resistance to toxin was found to correspond to a many-fold higher magnitude of protection against challenge with live vibrios. In the primary response the protection increased during the first month. Booster immunization gave rise to a further increased immunity which, however, declined rapidly. Multiple oral or repeated intraintestinal antigen administrations also induced protective antitoxic immunity although of less magnitude than that obtained by parenteral immunization. Enteral and, to a lesser extent, parenteral immunization gave rise to increased antitoxic antibody titers and immunoglobulin levels in intestinal washings and mucosa scraping. Immunoglobulin G (IgG) and IgG antitoxins predominated, but after enteral immunization total IgA and specific IgA antibodies occasionally reached levels similar to those for IgG. In serum, significantly increased antibody levels (IgG) were only recorded after parenteral immunization. Both the primary binding and the neutralizing antitoxin titers showed a stayistically significant correlation with the degree of protection against toxin challenge; however, for the neutralizing antibodies this correlation was not without exceptions. No relation to protection was found for intestinal antibodies. The results of the present study indicate that enternal as well as parenteral immunization with toxin antigen can give rise to effective cholera immunity. After enternal immunization, the protection appears to be medicated by locally synthesized antibodies. After parenteral vaccination both serum-derived and locally produced antibodies seem to be effective. PMID:54337

  5. Overexpression of CDKN1B inhibits fibroblast proliferation in a rabbit model of experimental glaucoma filtration surgery.

    PubMed

    Yang, Jian-gang; Deng, Ying; Zhou, Ling-xiao; Li, Xiao-yan; Sun, Peng-rui; Sun, Nai-xue

    2013-01-14

    To investigate the potential antiproliferative effect of cyclin-dependent kinase inhibitor 1B (CDKN1B) overexpression in a rabbit model of glaucoma filtration surgery (GFS). The recombinant adenovector expressing exogenous CDKN1B was delivered to Tenon's capsule by subconjunctival injection during unilateral filtration surgery. The time course of CDKN1B expression was monitored by immunohistochemistry and Western blot analysis. Evaluation of proliferating activity was performed by proliferating cell nuclear antigen (PCNA), argyrophilic nucleolar organizing region (AgNOR) staining, and fibroblast-specific protein 1 (FSP-1). Cyclin-dependent kinase 2 (Cdk2) and Cdk4 expression were detected with immunohistochemical analysis. The overexpression of CDKN1B in Tenon's capsule was monitored throughout the experimental period. Immunoreactivity to CDKN1B was mainly observed in the nucleus of fibroblasts. The increased expression of CDKN1B in sclera was detected up to 21 days after viral infection, whereas the level of CDKN1B protein in corneal stroma was not significantly increased. The overexpression of CDKN1B induced a significant decrease in AgNOR number/nucleus and area/nucleus, PCNA staining, FSP-1 positive cells, and the decreased expressions of Cdk2 and Cdk4, as evidenced by nuclear and cytoplasmic immunoreactivity to Cdk2 and Cdk4 antibodies in positive fibroblasts. The persistent overexpression of CDKN1B mediated by the recombinant adenovector expressing exogenous CDKN1B in Tenon's fibroblasts after GFS may lead to the inhibition of fibroblast proliferation and the downregulation of Cdk2 and Cdk4 activity, thereby reducing the severity of scar formation and the surgical outcome.

  6. Rabbit medicine.

    PubMed

    Jordan, Dinah G

    2007-01-01

    When filling prescriptions for a rabbit, it is important to know whether the rabbit is a pet or is being raised as a source of food for human consumption. Several drugs widely used for pet rabbits are prohibited from exralabel use in animals raised for food production. The list of banned drugs should always be perused prior to filling a prescription for a rabbit being raised for food production. Since no veterinary-approved products exist for rabbits and most medications must be compounded, pharmacists are likely to encounter prescriptions for rabbits in their practice. A basic understanding of rabbit anatomy, physiolgy and common diseases will assist pharmacists in distinguishing between safe and dangerous drugs for administration to rabbits.

  7. High speed intravascular photoacoustic imaging of atherosclerotic arteries (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Piao, Zhonglie; Ma, Teng; Qu, Yueqiao; Li, Jiawen; Yu, Mingyue; He, Youmin; Shung, K. Kirk; Zhou, Qifa; Kim, Chang-Seok; Chen, Zhongping

    2016-02-01

    Cardiovascular disease is the leading cause of death in the industrialized nations. Accurate quantification of both the morphology and composition of lipid-rich vulnerable atherosclerotic plaque are essential for early detection and optimal treatment in clinics. In previous works, intravascular photoacoustic (IVPA) imaging for detection of lipid-rich plaque within coronary artery walls has been demonstrated in ex vivo, but the imaging speed is still limited. In order to increase the imaging speed, a high repetition rate laser is needed. In this work, we present a high speed integrated IVPA/US imaging system with a 500 Hz optical parametric oscillator laser at 1725 nm. A miniature catheter with 1.0 mm outer diameter was designed with a 200 μm multimode fiber and an ultrasound transducer with 45 MHz center frequency. The fiber was polished at 38 degree and enclosed in a glass capillary for total internal reflection. An optical/electrical rotary junction and pull-back mechanism was applied for rotating and linearly scanning the catheter to obtain three-dimensional imaging. Atherosclerotic rabbit abdominal aorta was imaged as two frame/second at 1725 nm. Furthermore, by wide tuning range of the laser wavelength from 1680 nm to 1770 nm, spectroscopic photoacoustic analysis of lipid-mimicking phantom and an human atherosclerotic artery was performed ex vivo. The results demonstrated that the developed IVPA/US imaging system is capable for high speed intravascular imaging for plaque detection.

  8. [Clinical findings observed in rabbits, meat type, infected experimentally by Cystoisospora felis (Wenyon, 1923) Frenkel, 1977 (Apicomplexa: Cystoisosporinae)].

    PubMed

    da Costa, Paulo S; Munhoz, Alexandre D; Flausino, Walter; Lopes, Carlos Wilson G

    2006-01-01

    Twenty four rabbits type meat, cross-breed of White New Zealand and California, of both sexes, with age of 58 days old, and average weight of 1,586 g were used. Than, they were divided in three groups of eight rabbits each. The first group was inoculated orally, in two serial days, with 10(6) sporulated oocysts of Cystoisospora felis per animal, second group was considered per feed, and thirty group was left as control. Clinical signs as body weight, feed consumption, rectal temperature, and breathing frequency were taken daily. Carcasses weights were taking at 2, 4, 6, 8, 9, 16, 22 and 29 days after infection (DAI) when they were posted. In the first DAI, anorexia, slow movements, low percent of food consumption (85.76%), and of alimentary conversion were observed. Difference of 3.52% in the food consumption was observed between control and infected animals. The inoculated rabbits had high temperatures in the first DAI in comparison to controls and per fed animals (p<0.01) at 2nd and at 4th DAI. In relationship to the weight gain in the 1st week the carcasses of the infected rabbits had minimal difference in comparison to control animals. As conclusion, cystoisosporosis, beside clinical signs, can be interfered in the development of the rabbit.

  9. Disposable rabbit

    DOEpatents

    Lewis, Leroy C.; Trammell, David R.

    1986-01-01

    A disposable rabbit for transferring radioactive samples in a pneumatic transfer system comprises aerated plastic shaped in such a manner as to hold a radioactive sample and aerated such that dissolution of the rabbit in a solvent followed by evaporation of the solid yields solid waste material having a volume significantly smaller than the original volume of the rabbit.

  10. Disposal rabbit

    DOEpatents

    Lewis, L.C.; Trammell, D.R.

    1983-10-12

    A disposable rabbit for transferring radioactive samples in a pneumatic transfer system comprises aerated plastic shaped in such a manner as to hold a radioactive sample and aerated such that dissolution of the rabbit in a solvent followed by evaporation of the solid yields solid waste material having a volume significantly smaller than the original volume of the rabbit.

  11. Countercurrent transfer of dopamine from venous blood in the cavernous sinus to the arterial blood supplying the brain - the perfused rabbit head as an experimental model.

    PubMed

    Muszak, J; Krzymowski, T; Gilun, P; Stefanczyk-Krzymowska, S

    2014-10-01

    The objective of the current study was to check whether countercurrent transfer of dopamine occurs in the cavernous sinus of the rabbit and whether the rabbit can be used as an animal model to study cavernous sinus function. After exsanguination of the animal, oxygenated and warmed (37°C) Hanseneleit-Krebs buffer with autologous or homologous blood (in a 3:1 or 1:1 ratio) was pumped through both common carotid arteries into the head (60 ml/min; 80-100 mm Hg) and radiolabeled dopamine (3(H)-DA, 10 μCi) was infused into the cavernous sinus through the angular oculi vein. Cerebral blood from the basilar artery was collected from the cannulated vertebral artery during 3(H)-DA infusion and for 10 minutes after completion of infusion. Selected brain tissue samples were collected after completion of the head perfusion. It was demonstrated that dopamine can penetrate from the rabbit's cavernous sinus to the internal carotid artery supplying the brain. Dopamine permeation was greater when the rabbit head was perfused with buffer and blood in a 3:1 ratio than with 1:1 (P<0.01). When the head was perfused with buffer and blood in a 3:1 ratio, significant radioactivity was found in samples collected from the brain basilar artery during and after 3(H)-DA infusion (P<0.001). The radioactivity was identified as 34.13 ± 2.7% unmetabolized 3(H)-DA and 65.9 ± 2.7% its metabolites. Significant radioactivity was also found in some brain tissue samples in both groups (P<0.05). The concentration of free radiolabeled dopamine particles in the dialysate of blood plasma and plasma diluted with buffer did not differ significantly. Because the structures of the cavernous sinus and cavernous fragment of the internal carotid artery of the rabbit are similar to those in humans, it suggests that rabbits can serve as a model for experimental physiological studies of cavernous sinus function and retrograde dopamine transfer in the cavernous sinus should be considered as an important link in

  12. [Para-aminobenzoic acid in therapy of experimental keratitis caused by herpes simplex virus in rabbits: the therapeutic effect and decrease of infectious titer].

    PubMed

    Akberova, S I; Leont'eva, N A; Stroeva, O G; Galegov, G A

    1996-01-01

    Para-aminobenzoic acid (PABA) in low concentrations exerted an antiherpetic effect with a good therapeutic result in rabbits with experimental keratoconjunctivitis caused by herpes simplex virus (HSV) (experimental group). In group 2 (control) 0.9% NaCl solution was used as placebo. The animals were infected by instillation of HSV-1 on the cornea predissected with a bifurcation needle. The severity of keratitis was assessed in scores after A. A. Kasparov et al. PABA and placebo were administered starting from day 3 postinfection as subconjunctival injections and then instillations. In experimental group (5 rabbits, 10 eyes) the degree of keratitis reduced from 3.0 +/- 0.2 to 1.7 +/- 0.1 points within the first 4 days. Complete epithelialization was over by day 4.4 +/- 0.4, clinical cure was attained by days 12-13. In control group (6 rabbits, 12 eyes) erosion of the cornea and severity of keratitis increased from 2.9 +/- 0.07 to 3.8 +/- 0.2 points by day 4 postinoculation after placebo was started, after which it reduced; epithelialization was over by day 8.2 +/- 0.3, clinical cure by days 13-14. Infective titer in the cornea was determined in VERO cell culture from the degree of virus-induced cytopathogenic effect and expressed in lgTCE50. On day 13 this parameter was reliably higher in the control group in comparison with the experimental (3.2 vs. 1.8), this confirming the virucidal effect of PABA.

  13. An overview on development and application of an experimental platform for quantitative cardiac imaging research in rabbit models of myocardial infarction

    PubMed Central

    Feng, Yuanbo; Bogaert, Jan; Oyen, Raymond

    2014-01-01

    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. PMID:25392822

  14. Systemic Neutralization of Interleukin-8 Markedly Reduces Neutrophilic Pleocytosis during Experimental Lipopolysaccharide-Induced Meningitis in Rabbits

    PubMed Central

    Dumont, Rachel A.; Car, Bruce D.; Voitenok, Nikolai N.; Junker, Ursula; Moser, Bernhard; Zak, Oto; O'Reilly, Terence

    2000-01-01

    Interleukin-8 (IL-8) is elevated in the cerebrospinal fluid (CSF) of patients with meningitis and is proposed to participate in subarachnoid-space pleocytosis. However, intracisternal injection of IL-8 into rabbits failed to induce indices typical of meningitis (leukocyte, tumor necrosis factor, or protein accumulation in the CSF or histopathological changes), indicating that merely increasing the CSF level of this chemokine is insufficient to induce inflammation in this anatomical site. IL-8 treatment did not affect inflammatory responses to subsequently intracisternally administered lipopolysaccharide (LPS). IL-8 was chemotactic for rabbit neutrophils in vitro, and subcutaneous injection of IL-8 (diluted in buffer or CSF) proved the in vivo activity of this peptide and suggested the absence of an IL-8 inhibitor in normal rabbit CSF. LPS-dependent pleocytosis was only slightly diminished by intracisternally administered murine anti-rabbit IL-8 monoclonal antibody (MAb) WS-4 but was dramatically reduced by intravenously administered MAb. Therefore, elevated CSF IL-8 levels may contribute to, but cannot solely account for, neutrophil influx into the subarachnoid space during meningitis. However, inhibition of IL-8 activity of the bloodstream side of the blood-brain barrier effectively reduces pleocytosis, indicating a central role of IL-8 in neutrophil influx into CSF during bacterial meningitis. Thus, inhibition of IL-8 is a possible therapeutic target for adjunct treatment of meningitis. PMID:10992482

  15. [Experimental study of core binding factor a1 gene-modified rabbit skin fibroblasts enhance bone defect repair].

    PubMed

    Xiao, De-chang; Deng, Lian-fu; Yang, Qing-ming; Tan, Yan-bin; Lü, Xue-min; Zhang, Wei; Feng, Wei; He, Ya-feng; Liang, Jing; Zhu, Ya-ping; Qi, Jin; Zhou, Qi; Wang, Jun

    2007-11-15

    To investigate bone defect healing by true bone ceramic complex carrying core binding factor a1 (Cbfa1) gene modified rabbit skin fibroblasts. Transfect rabbit skin fibroblasts (RSF) with both eukaryotic expression vector pSG5 which could express Cbfa1 gene and pSG5. After being cultured for 48 h, the transfected RSF were seeded into true bone ceramic (TBC) of 2 cm in length and 4 mm in diameter to construct pSG5-Cbfa1/RSF/TBC complex and pSG5/RSF/TBC complex. Forty-eight bone defect model rabbits were randomized into four groups, each has 6 rabbits (12 radius), due to different treatment. group I: with pSG5-Cbfa1/RSF/TBC complex, group II: with pSG5/RSF/TBC complex, group III: with TBC, Group IV: empty control. After being seeded and cultured for about 24 h the complexes were implanted into 2 cm long bone defects in the middle of bilateral radius of rabbits. The radius were inspected by X-ray and then the specimens were collected at the end of the fourth and twelfth weeks after operation. Then, the specimens were decalcified and histologically investigated with Hematoxylin eosin staining and Masson staining methods. Newly synthesized trabecular bone was inspected by image analysis system and the strength of bone defect area treated with graft-implantation was tested with biomechanical method-three point bending test. In group I, trabecular bone was actively synthesized to generate a great amount of trabecular bone and osteon. Preliminary union and bone defect healing were completed with good biomechanical characteristics. There were no newly synthesized trabecular in the other three groups, and bone defect healing were not discovered. The amount of newly synthesized trabecular bone and the results of biomechanical testing differed significantly between group I and the other three (P < 0.01). The efficacy of group I was significantly better than that of the other three groups. True bone ceramic complex composed with Cbfa1 gene modified rabbit skin fibroblasts can

  16. Anti-inflammatory and antioxidant effects of Tualang honey in alkali injury on the eyes of rabbits: Experimental animal study

    PubMed Central

    2011-01-01

    Background Alkali injury is one of the most devastating injuries to the eye. It results in permanent unilateral or bilateral visual impairment. Chemical eye injury is accompanied by an increase in the oxidative stress. Anti-inflammatory and antioxidant agents play a major role in the treatment of chemical eye injuries. The purpose of this study is to evaluate the anti-inflammatory (clinical and histopathological) and antioxidant effects of Tualang honey versus conventional treatment in alkali injury on the eyes of rabbits. Methods A preliminary study was carried out prior to the actual study to establish the alkali chemical injury on rabbit's cornea and we found that alkali chemical injury with 2 N NaOH showed severe clinical inflammatory features. In actual study, alkali injury with 2 N NaOH was induced in the right eye of 10 New Zealand White rabbits' cornea. The rabbits were divided into two groups, Group A was given conventional treatment and Group B was treated with both topical and oral Tualang honey. Clinical inflammatory features of the right eye were recorded at 12 hours, 24 hours, 72 hours, 5th day and 7th day post induction of alkali burn on the cornea. The histopathological inflammatory features of the right corneas of all rabbits were also evaluated on day-7. The level of total antioxidant status and lipid peroxidation products in the aqueous humour, vitreous humour and serum at day-7 were estimated biochemically. Fisher's Exact, Chi-Square and Mann-Whitney test were used to analyse the data. Results There was no statistically significant difference in clinical inflammatory features (p > 0.05) between honey treated and the conventional treated group at different times of examination. Histopathological examination of the cornea showed the number of polymorphonuclear leucocytes was below 50 for both groups (mild grade). There was also no significant difference in the level of total antioxidant status as well as lipid peroxidation products in aqueous

  17. Enhanced Ablation of High Intensity Focused Ultrasound with Microbubbles: An Experimental Study on Rabbit Hepatic VX2 Tumors

    SciTech Connect

    He Wei; Wang Wei Zhou Ping; Wang, Yixiang J.; Zhou Peng; Li Ruizhen; Wang Jinsheng; Ahuja, Anil T.

    2011-10-15

    Purpose: This study was designed to assess the enhanced effect of high intensity focused ultrasound (HIFU) ablation with microbubbles on rabbit hepatic VX2 tumors and to compare the detection sensitivity of CEUS and CECT to determine the residual viable tissue after ablation of HIFU. Methods: Forty rabbits with hepatic VX2 tumors were randomly separated into two groups (20 animals per group) before HIFU ablation. A bolus of 0.2 mL of saline or a microbubble-based ultrasound (US) contrast agent was injected intravenously to group I rabbits and group II rabbits, respectively. The HIFU ablation procedure was started 15 s after the injection. Tumors were examined with grayscale contrast-enhanced ultrasound (CEUS) and contrast-enhanced computed tomography (CECT) immediately before and after HIFU ablation. Histopathologic assessment was performed immediately after treatment imaging. Results: Before ablation, intense contrast enhancement during arterial phase was observed at the whole tumors or the periphery of the tumors by CEUS and CECT. Lower HIFU energy was used in group II than in group I (P < 0.001). Histopathologic assessment revealed local residual viable tumor tissues due to incomplete ablation in 47.4% (9/19) of tumors in group I and 10% (2/20) of tumors in group II (P < 0.05). The concordance rate of CEUS (90.9%) with histopathology on residual tumor detection was higher than that of CECT (27.3%, P < 0.05). Conclusions: Introduction of the microbubble agent enhances HIFU therapeutic efficacy. CEUS proves to have high sensitivity in assessment of residual viable rabbit VX2 tumor after HIFU.

  18. Experimental scoliosis in the course of unilateral surface electrostimulation of the paravertebral muscles in rabbits: effects according to stimulation period.

    PubMed

    Kowalski, I M; Szarek, J; Zarzycki, D; Rymarczyk, A

    2001-12-01

    Scoliosis among children and adolescents is a persistent problem. Worldwide, it afflicts between 0.3 to 15.3% of the population. One of the treatment methods of this disorder is to administer lateral electrical surface stimulation (LESS) for 9 h/day; unfortunately, however, this results in side-effects. Improvements are therefore sought. The main aim of the study was to investigate the effects of the duration of LESS on scoliosis progression and to evaluate, qualitatively, any associated macroscopic effect on other internal organs. The length of the LESS period was based on the results of previous clinical trials in children. The experiment was performed on 13 developing rabbits (aged 3.5 months), divided into three groups: group 1, rabbits subsequently treated for 9 h/day (n=5); group 2, animals treated for 2 h/day (n=5); group 3, control rabbits without electrostimulation (n=3). Stimulation was carried out using an electric stimulator SCOL-2 according to the method modified by Kowalski. The animals were killed after 3 months and examined macroscopically, and their adrenal glands were dissected and weighed. The X-rays of the spine of the animals were taken to analyse spinal deformity. Macroscopic lesions in rabbits from groups 2 and 3 (control) were mostly absent. While there was considerable deviation in group 1, all the stress features were apparent. The enlargement of the adrenal glands observed in group 2 was significantly less marked than in group 1. The degree of scoliotic deformity (according to the Cobb method) ranged from 21 degrees to 410 degrees (mean, 31.2 degrees) and from 23 degrees to 330 degrees (mean, 30 degrees) in groups 1 and 2, respectively. LESS resulted in spinal deformity to a similar degree in the rabbits treated for either 9 or 2 h/day over a 3-month period. Short LESS therapy (2 h/day) significantly reduced detrimental effects associated with the treatment on internal organs of laboratory animals.

  19. Noninvasive detection of lipids in atherosclerotic plaque using ultrasound thermal strain imaging: in vivo animal study

    PubMed Central

    Mahmoud, Ahmed M.; Dutta, Debaditya; Lavery, Linda; Stephens, Douglas N.; Villanueva, Flordeliza S.; Kim, Kang

    2013-01-01

    Objectives This study examined the feasibility of in vivo detection of lipids in atherosclerotic plaque (AP) by ultrasound (US) thermal strain imaging (TSI). Background Intraplaque lipid content is thought to contribute to plaque stability. Lipid exhibits a distinctive physical characteristic of temperature-dependent US speed compared to water-bearing tissues. As tissue temperature changes, US radiofrequency (RF) echoes shift in time of flight which produces an apparent strain (temporal or thermal strain: TS). Methods US heating-imaging pulse sequences and transducers were designed and integrated into commercial US scanners for US-TSI of arterial segments. US-RF data were collected while gradually increasing tissue temperature. Phase-sensitive speckle tracking was applied to reconstruct TS maps co-registered to B-scans. Segments from injured atherosclerotic and uninjured non-atherosclerotic common femoral arteries (CFA) in cholesterol fed New Zealand rabbits, and segments from control normal diet fed rabbits (n=14 total) were scanned in vivo at different time points up to 12 weeks. Results Lipid-rich atherosclerotic lesions exhibited distinct positive TS (+0.19±0.08%) compared with that in non-atherosclerotic (−0.10±0.13%) and control (−0.09±0.09%) segments (p<0.001). US-TSI enabled serial monitoring of lipids during atherosclerosis development. The co-registered set of morphological and compositional information of US-TSI showed good agreement with histology. Conclusions US-TSI successfully detected and longitudinally monitored lipid progression in atherosclerotic CFA. US-TSI of relatively superficial arteries may be a modality that could be integrated into a commercial US system for noninvasive lipid detection in AP. PMID:23916926

  20. Effective protection induced by three different versions of the porcine S3Pvac anticysticercosis vaccine against rabbit experimental Taenia pisiformis cysticercosis.

    PubMed

    Betancourt, Miguel Angel; de Aluja, Aline S; Sciutto, Edda; Hernández, Marisela; Bobes, Raúl J; Rosas, Gabriela; Hernández, Beatriz; Fragoso, Gladis; Hallal-Calleros, Claudia; Aguilar, Liliana; Flores-Peréz, Iván

    2012-04-05

    In an effort to develop an effective and affordable oral vaccine against porcine Taenia solium cysticercosis, the S3Pvac anti-cysticercosis vaccine was expressed in papaya calli. Taenia pisiformis experimental rabbit cysticercosis was used as a model to compare the efficacy of the oral vaccine vs. the injectable S3Pvac-synthetic and S3Pvac-phage versions. Oral S3Pvac-papaya significantly reduced the expected number of hepatic lesions and peritoneal cysticerci to a similar extent than the injectable vaccines. This study reports for the first time an effective oral vaccine against T. pisiformis cysticercosis, possibly useful against porcine T. solium cysticercosis.

  1. Cap buckling as a potential mechanism of atherosclerotic plaque vulnerability.

    PubMed

    Abdelali, Maria; Reiter, Steven; Mongrain, Rosaire; Bertrand, Michel; L'Allier, Philippe L; Kritikou, Ekaterini A; Tardif, Jean-Claude

    2014-04-01

    Plaque rupture in atherosclerosis is the primary cause of potentially deadly coronary events, yet about 40% of ruptures occur away from the plaque cap shoulders and cannot be fully explained with the current biomechanical theories. Here, cap buckling is considered as a potential destabilizing factor which increases the propensity of the atherosclerotic plaque to rupture and which may also explain plaque failure away from the cap shoulders. To investigate this phenomenon, quasistatic 2D finite element simulations are performed, considering the salient geometrical and nonlinear material properties of diverse atherosclerotic plaques over the range of physiological loads. The numerical results indicate that buckling may displace the location of the peak von Mises stresses in the deflected caps. Plaque buckling, together with its deleterious effects is further observed experimentally in plaque caps using a physical model of deformable mock coronary arteries with fibroatheroma. Moreover, an analytical approach combining quasistatic equilibrium equations with the Navier-Bresse formulas is used to demonstrate the buckling potential of a simplified arched slender cap under intraluminal pressure and supported by foundations. This analysis shows that plaque caps - calcified, fibrotic or cellular - may buckle in specific undulated shapes once submitted to critical loads. Finally, a preliminary analysis of intravascular ultrasonography recordings of patients with atherosclerotic coronary arteries corroborates the numerical, experimental and theoretical findings and shows that various plaque caps buckle in vivo. By displacing the sites of high stresses in the plaque cap, buckling may explain the atherosclerotic plaque cap rupture at various locations, including cap shoulders.

  2. Effects of alpha-tocopherol and astaxanthin on LDL oxidation and atherosclerosis in WHHL rabbits.

    PubMed

    Jacobsson, Leif S; Yuan, Xi Ming; Ziedén, Bo; Olsson, Anders G

    2004-04-01

    The aim of this study was to evaluate the influence of -tocopherol and astaxanthin on low-density lipoprotein (LDL) oxidation lag time and atherosclerotic lesion formation in Watanabe heritable hyperlipidemic (WHHL) rabbits. Thirty-one, 3-month-old WHHL rabbits were divided into three experimental groups. One group (n=10) was fed standard rabbit feed alone and served as a control, a second group (n=11) was supplied with the same feed containing 500 mg alpha-tocopherol/kg and a third group (n=10) was given a feed containing 100 mg astaxanthin/kg. Plasma lipids, lipoproteins and LDL oxidation lag time were followed for 24 weeks. At the end of the treatment period, the animals were killed and the thoracic aorta was used for evaluation of the degree of atherosclerosis. Colour photographs of the intimal surface of the vessel were taken for determination of the atherosclerotic area. Cross-sections of the thoracic aorta were used for histological examination and for determination of intimal thickening. Specimens of the vessel were used for determination of the tissue cholesterol content. Plasma cholesterol remained at a high level during the time of the experiment and there were no differences between the experimental groups. After 24 weeks, the LDL oxidation lag time was 53.7+/-1.7 min, 109+/-4 min (P<0.001) and 56.4+/-3.4 min (P=0.47) in the control, alpha-tocopherol and astaxanthin groups, respectively. In the thoracic aorta, the atherosclerotic area was 80.7+/-5.1%, 67.1+/-6.7% (P=0.13) and 75.2+/-5.7% (P=0.49) in the control, alpha-tocopherol and astaxanthin groups, respectively. The intimal thickening was 45.6+/-3.2%, 44.0+/-4.1% (P=0.89) and 40.0+/-4.5% (P=0.33) in the control, alpha-tocopherol and astaxanthin groups, respectively. Finally, the cholesterol content was 107+/-9 mol/g, 95.7+/-11.5 mol/g (P=0.31) and 101+/-5 mol/g (P=0.33) in the control, alpha-tocopherol and astaxanthin groups, respectively. It can be concluded that alpha-tocopherol but not

  3. A combination of experimental and numerical methods to investigate the role of strain rate on the mechanical properties and collagen fiber orientations of the healthy and atherosclerotic human coronary arteries.

    PubMed

    Karimi, Alireza; Rahmati, Seyyed Mohammadali; Sera, Toshihiro; Kudo, Susumu; Navidbakhsh, Mahdi

    2017-03-04

    Atherosclerosis enables to alter not only the microstructural but also the physical properties of the arterial walls by plaque forming. Few studies so far have been conducted to calculate the isotropic or anisotropic mechanical properties of the healthy and atherosclerotic human coronary arteries. To date there is a paucity of knowledge on the mechanical response of the arteries under different strain rates. Therefore, the objective of the concurrent research was to comprehend whether the alteration in the strain rates of the human atherosclerotic arteries in comparison with the healthy ones contribute to the biomechanical behaviors. To do this, healthy and atherosclerotic human coronary arteries were removed from 18 individuals during autopsy. Histological analyses by both an expert histopathologist and an imaged-based recognizer software were performed to figure out the average angle of collagen fibers in the healthy and atherosclerotic arterial walls. Thereafter, the samples were subjected to 3 diverse strain rates, i.e., 5, 20, and 50 mm/min, until the material failure occurs. The stress-strain diagrams of the arterial tissues were calculated in order to capture their linear elastic and nonlinear hyperelastic mechanical properties. In addition, Artificial Neural Networks (ANNs) was employed to predict the alteration of mean angle of collagen fibers during load bearing up to failure. The findings suggest that strain rate has a significant (p < 0.05) role in the linear elastic and nonlinear hyperelastic mechanical properties as well as the mean angle of collagen fibers of the atherosclerotic arteries, whereas no specific impact on the healthy ones. Furthermore, the mean angle of collagen fibers during the load bearing up to the failure at each strain rate was well predicted by the proposed ANNs code.

  4. A combination of experimental and numerical methods to investigate the role of strain rate on the mechanical properties and collagen fiber orientations of the healthy and atherosclerotic human coronary arteries

    PubMed Central

    Karimi, Alireza; Rahmati, Seyyed Mohammadali; Sera, Toshihiro; Kudo, Susumu; Navidbakhsh, Mahdi

    2017-01-01

    ABSTRACT Atherosclerosis enables to alter not only the microstructural but also the physical properties of the arterial walls by plaque forming. Few studies so far have been conducted to calculate the isotropic or anisotropic mechanical properties of the healthy and atherosclerotic human coronary arteries. To date there is a paucity of knowledge on the mechanical response of the arteries under different strain rates. Therefore, the objective of the concurrent research was to comprehend whether the alteration in the strain rates of the human atherosclerotic arteries in comparison with the healthy ones contribute to the biomechanical behaviors. To do this, healthy and atherosclerotic human coronary arteries were removed from 18 individuals during autopsy. Histological analyses by both an expert histopathologist and an imaged-based recognizer software were performed to figure out the average angle of collagen fibers in the healthy and atherosclerotic arterial walls. Thereafter, the samples were subjected to 3 diverse strain rates, i.e., 5, 20, and 50 mm/min, until the material failure occurs. The stress-strain diagrams of the arterial tissues were calculated in order to capture their linear elastic and nonlinear hyperelastic mechanical properties. In addition, Artificial Neural Networks (ANNs) was employed to predict the alteration of mean angle of collagen fibers during load bearing up to failure. The findings suggest that strain rate has a significant (p < 0.05) role in the linear elastic and nonlinear hyperelastic mechanical properties as well as the mean angle of collagen fibers of the atherosclerotic arteries, whereas no specific impact on the healthy ones. Furthermore, the mean angle of collagen fibers during the load bearing up to the failure at each strain rate was well predicted by the proposed ANNs code. PMID:27588460

  5. Quantitative dynamic contrast enhanced MRI of experimental synovitis in the rabbit knee: comparison of macromolecular blood pool agents vs. Gadolinium-DOTA.

    PubMed

    Watrin-Pinzano, Astrid; Loeuille, Damien; Goebel, Jean-Christophe; Lapicque, Françoise; Walter, Fredéric; Robert, Philippe; Netter, Patrick; Corot, Claire; Gillet, Pierre; Blum, Alain

    2008-01-01

    The purpose of this study was to assess 2 Gd-based macromolecular intravascular contrast agents (P792, rapid clearance blood pool agent (rBPA) and P717, slow clearance blood pool agent (sBPA)) compared to Gd-DOTA (representative extracellular non specific agent) in MR imaging of knee rabbit experimental synovitis. Quantitative dynamic contrast enhanced MRI (qDCE-MRI) after intravascular injection of a low molecular weight contrast agent of 0.56 kDa (Gd-DOTA) and 2 high-molecular-weight contrast agents of 6.47 kDa (P792) and 52 kDa (P717) was performed in rabbits with carrageenan-induced synovitis of the right knee. P792 and P717 provided a progressive and persistent enhancement of arthritic synovial tissue while Gd-DOTA provided an early and rapidly declining enhancement with a concomitant diffusion in synovial fluid, thus limitating delineation of synovial pannus. P792 allowed acquisition of high-quality MR arthrograms, due to both a better diffusion in synovial pannus (vs. P717) and a concomitant restricted diffusion into the synovial fluid (vs. Gd-DOTA). In fact, experimental rabbit synovitis represent a specific entity that favors the T1 effect of high-molecular-weight agents, and especially rBPA P792, entrapped in synovial pannus, without diffusion in the synovial fluid. Due to this lack of arthrographic effect, P792 accumulation could be specifically sequentially analyzed by qDCE-MRI for detecting, characterizing and monitoring synovial vascular permeability changes during mono- or polysynovitis.

  6. The impact of orthopedic device associated with carbonated hydroxyapatite on the oxidative balance: experimental study of bone healing rabbit model.

    PubMed

    Jebahi, Samira; Nsiri, Riadh; Boujbiha, Mohammed; Bouroga, Ezedine; Rebai, Tarek; Keskes, Hassib; El Feki, Abdelfattah; Oudadesse, Hassane; El Feki, Hafed

    2013-10-01

    Orthopedic devices are used in pathologic disorder as an adjunct to bone grafts to provide immediate structural stability. Unfortunately, the use of metallic devices has some complications. This study aimed to characterize the oxidative stress biomarker and the antioxidant enzyme profiles during bone regeneration. New Zealand White rabbits were divided into 4 groups: Group (I) was used as control (T), Groups II, III, and IV were used, respectively, as implanted tissue with carbonated hydroxyapatite (CHA), carbonated hydroxyapatite associated with external fixator (CHA + EF), and presenting empty defects (ED). Grafted bone tissues were carefully removed to measure malondialdehyde (MDA) concentration, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase activities (GPx). Our results showed that 4 weeks after operation, treatment of rabbits with CHA + EF showed a significantly higher malondialdehyde (MDA) concentration when compared to that of control group. The SOD, CAT, and GPx in CHA + EF group showed significantly lower activities when compared to those in control group. Eight weeks after surgery, the CHA + EF group presented a lower concentration of MDA as compared to those seen after the first 4 weeks after surgery. On the other hand, the SOD, CAT, and GPx showed a higher activity when compared with the same group. Consequently, MDA concentration and the antioxidant enzyme activities were not significant (p > 0.05) when compared to those in control group rabbits. Histologic sampling has demonstrated successful time-patterned resorption accompanied by bone replacement and remodeling. These results suggest that there was a temporary increase in the oxidative marker level in CHA + EF healing bone and the 8-week period was sufficient to re-establish oxidant-antioxidant balance accompanied by bone repair in the tibia rabbit model.

  7. Modeling of transfer kinetics at the serum-cerebrospinal fluid barrier in rabbits with experimental meningitis: application to grepafloxacin.

    PubMed

    Pfister, Marc; Zhang, Liping; Hammarlund-Udenaes, Margareta; Sheiner, Lewis B; Gerber, Cynthia M; Täuber, Martin G; Cottagnoud, Philippe

    2003-01-01

    The goals of the present study were to model the population kinetics of in vivo influx and efflux processes of grepafloxacin at the serum-cerebrospinal fluid (CSF) barrier and to propose a simulation-based approach to optimize the design of dose-finding trials in the meningitis rabbit model. Twenty-nine rabbits with pneumococcal meningitis receiving grepafloxacin at 15 mg/kg of body weight (intravenous administration at 0 h), 30 mg/kg (at 0 h), or 50 mg/kg twice (at 0 and 4 h) were studied. A three-compartment population pharmacokinetic model was fit to the data with the program NONMEM (Nonlinear Mixed Effects Modeling). Passive diffusion clearance (CL(diff)) and active efflux clearance (CL(active)) are transfer kinetic modeling parameters. Influx clearance is assumed to be equal to CL(diff), and efflux clearance is the sum of CL(diff), CL(active), and bulk flow clearance (CL(bulk)). The average influx clearance for the population was 0.0055 ml/min (interindividual variability, 17%). Passive diffusion clearance was greater in rabbits receiving grepafloxacin at 15 mg/kg than in those treated with higher doses (0.0088 versus 0.0034 ml/min). Assuming a CL(bulk) of 0.01 ml/min, CL(active) was estimated to be 0.017 ml/min (11%), and clearance by total efflux was estimated to be 0.032 ml/min. The population kinetic model allows not only to quantify in vivo efflux and influx mechanisms at the serum-CSF barrier but also to analyze the effects of different dose regimens on transfer kinetic parameters in the rabbit meningitis model. The modeling-based approach also provides a tool for the simulation and prediction of various outcomes in which researchers might be interested, which is of great potential in designing dose-finding trials.

  8. Anatomical features for an adequate choice of experimental animal model in biomedicine: II. Small laboratory rodents, rabbit, and pig.

    PubMed

    Lossi, Laura; D'Angelo, Livia; De Girolamo, Paolo; Merighi, Adalberto

    2016-03-01

    The anatomical features distinctive to each of the very large array of species used in today's biomedical research must be born in mind when considering the correct choice of animal model(s), particularly when translational research is concerned. In this paper we take into consideration and discuss the most important anatomical and histological features of the commonest species of laboratory rodents (rat, mouse, guinea pig, hamster, and gerbil), rabbit, and pig related to their importance for applied research.

  9. Progress in atherosclerotic plaque imaging

    PubMed Central

    Soloperto, Giulia; Casciaro, Sergio

    2012-01-01

    Cardiovascular diseases are the primary cause of mortality in the industrialized world, and arterial obstruction, triggered by rupture-prone atherosclerotic plaques, lead to myocardial infarction and cerebral stroke. Vulnerable plaques do not necessarily occur with flow-limiting stenosis, thus conventional luminographic assessment of the pathology fails to identify unstable lesions. In this review we discuss the currently available imaging modalities used to investigate morphological features and biological characteristics of the atherosclerotic plaque. The different imaging modalities such as ultrasound, magnetic resonance imaging, computed tomography, nuclear imaging and their intravascular applications are illustrated, highlighting their specific diagnostic potential. Clinically available and upcoming methodologies are also reviewed along with the related challenges in their clinical translation, concerning the specific invasiveness, accuracy and cost-effectiveness of these methods. PMID:22937215

  10. Safety of medium-chain triglycerides used as an intraocular tamponading agent in an experimental vitrectomy model rabbit.

    PubMed

    Auriol, Sylvain; Mahieu, Laurence; Brousset, Pierre; Malecaze, François; Mathis, Véronique

    2013-01-01

    To evaluate safety of medium-chain triglycerides used as a possible intraocular tamponading agent. A 20-gauge pars plana vitrectomy was performed in the right eye of 28 rabbits. An ophthalmologic examination was performed every week until rabbits were killed. At days 7, 30, 60, and 90, rabbits were killed and the treated eyes were examined macroscopically and prepared for histologic examination. Principal outcome was retinal toxicity evaluated by light and electron microscopy, and secondary outcomes were the presence of medium-chain triglyceride emulsification, inflammatory reactions, and the development of cataract. Histologic examination did not reveal any retinal toxicity. Two cases of moderate emulsification were observed, but in these cases, emulsification was caused by the perioperative injection of the agent and did not increase during the postoperative period. We noted 13 cases of inflammatory reaction in vitreous cavity and no case of inflammatory reaction in anterior chamber. Two eyes developed cataract as a result of perioperative trauma to the lens with the vitreous cutter and not secondary to the presence of medium-chain triglycerides in the vitreous cavity. Medium-chain triglycerides did not induce morphologic evidence of retinal toxicity. The results suggest that medium-chain triglycerides could be a promising alternative intraocular tamponading agent for the treatment of retinal detachments.

  11. Urethral Reconstruction Using Mesothelial Cell-Seeded Autogenous Granulation Tissue Tube: An Experimental Study in Male Rabbits

    PubMed Central

    Jiang, Shiwei; Xu, Zhonghua; Zhao, Yuanyuan; Yan, Lei; Zhou, Zunlin

    2017-01-01

    Objective. This study was to evaluate the utility of the compound graft for tubularized urethroplasty by seeding mesothelial cells onto autogenous granulation tissue. Methods. Silastic tubes were implanted subcutaneously in 18 male rabbits, of which nine underwent omentum biopsies simultaneously for in vitro expansion of mesothelial cells. The granulation tissue covering the tubes was harvested 2 weeks after operation. Mesothelial cells were seeded onto and cocultured with the tissue for 7 days. A pendulous urethral segment of 1.5 cm was totally excised. Urethroplasty was performed with mesothelial cell-seeded tissue tubes in an end-to-end fashion in nine rabbits and with unseeded grafts in others as controls. Serial urethrograms were performed at 1, 2, and 6 months postoperatively. Meanwhile, the neourethra was harvested and analyzed grossly and histologically. Results. Urethrograms showed cell-seeded grafts maintained wide at each time point, while strictures formation was found in unseeded grafts. Histologically, layers of urothelium surrounded by increasingly organized smooth muscles were observed in seeded grafts. In contrast, myofibroblasts accumulation and extensive scarring occurred in unseeded grafts. Conclusions. Mesothelial cell-seeded granulation tissue tube can be successfully used for tubularized urethroplasty in male rabbits. PMID:28337443

  12. Intraocular transplantation of human adipose-derived mesenchymal stem cells in a rabbit model of experimental retinal holes.

    PubMed

    Xuqian, W; Kanghua, L; WeiHong, Y; Xi, Y; Rongping, D; Qin, H; Fangtian, D; Chunhua Zhao, Robert

    2011-10-01

    To investigate whether human adipose-derived mesenchymal stem cell (hAD-MSC) transplantation would ameliorate the healing process of a rabbit model of retinal holes. Retinal holes were made in the left eyes of 20 New Zealand white rabbits and randomly filled by hAD-MSCs (transplantation group) or phosphate-buffered saline (control group), respectively. Frequency-domain optical coherence tomography (OCT) scan was performed on days 2, 4, 12, 20 and 32 postoperatively, and immunofluorescence was performed on days 12 and 32 to further identify the cell types of the injured area. Frequency-domain OCT scan showed that the mean center thickness of the reconstructed tissue reached a normal level on day 12 in the transplantation group, while in the control group, the mean center thickness was normal on day 32. Furthermore, compared to the control group where only anti-glial fibrillary acidic protein-labeled glial-like cells were detected, donor-derived opsin-positive photoreceptor-like cells and protein kinase C-positive bipolar-like cells were sporadically found in the transplantation group. Transplanted hAD-MSCs could engraft in the retinal hole of a rabbit model, and clearly accelerated the healing process and ameliorated injury recovery. Copyright © 2011 S. Karger AG, Basel.

  13. [Results of the IOP decrease after application of some mixtures of amino acids and antiglaucomatics in rabbits (a review of experimental publications)].

    PubMed

    Oláh, Z; Veselovský, J

    2011-01-01

    To summarise of experimental results performed on rabbit eyes focused to influence the physiological intraocular pressure (lOP) after application of some amino acids mixture with some regularly used antiglaucomatics. The experiments were performed on adult rabbits (female of the New Zealand White species). The applicated substances were: 10% solution of amino acids (L-lysin.2HCl.2H2O, L-arginine.HCL or L-glycine.HCL) in antiglau-comatics 0.5% timolol (Timoptol) or 0.005% latanoprost (Xalatan). This mixture was applicated to the left eye; right eye was used as control. The measurement of IOP and pupil diameter was performed before instillation, in 15th, 30th, 60th, 180th, 240th minute and 24 hours after application. Functional bioactivity of the used antiglaucomatics in case of decreased lOP is rising after interaction with the relevant specific amino acid. Glycine in timolol showed the highest effect on average decrease of the lOP physiological values (lOP decrease reached - 5,5 torr) followed by arginine in timolol (lOP decrease reached - 3,3 torr). The lOP decrease after other combinations of amino acids and antiglaucomatics was in average lower or nonsignificant. Through interaction between in vitro prepared mixture free amino acids and antiglaucomatics a new, biologically active substance (metabolite) is created. After instillation in experimental condition achieving stronger and longer decrease of the lOP compared with a single antiglaucomatic or amino acid.

  14. Iodine-125 Seeds Strand for Treatment of Tumor Thrombus in Inferior Vena Cava: An Experimental Study in a Rabbit Model

    SciTech Connect

    Zhang, Wen Yan, Zhiping Luo, Jianjun Fang, Zhuting Wu, Linlin Liu, QingXin Qu, Xudong Liu, Lingxiao Wang, Jianhua

    2013-10-15

    Objective: The purpose of this study was to establish an animal model of implanted inferior vena cava tumor thrombus (IVCTT) and to evaluate the effect of linear iodine-125 seeds strand in treating implanted IVCTT. Methods: Tumor cell line VX{sub 2} was inoculated subcutaneously into New Zealand rabbit to develop the parent tumor. The tumor strip was inoculated into inferior vena cava (IVC) to establish the IVCTT model. The IVCTT was confirmed by multidetector computed tomography (MDCT) after 2 weeks. Twelve rabbits with IVCTT were randomly divided into two groups. Treatment group (group T; n = 6) underwent Iodine-125 seeds brachytherapy, and the control group (group C; n = 6) underwent blank seeds strand. The blood laboratory examination (including blood routine examination, hepatic and renal function), body weight, survival time, and IVCTT volume by MDCT were monitored. All rabbits were dissected postmortem, and the therapeutic effects were evaluated on the basis of histopathology. The proliferating cell nuclear antigen index (PI) and apoptosis index (AI) of IVCTT were compared between two groups. T test, Wilcoxon rank test, and Kaplan-Meier survival curve analysis were used. Results: The success rate of establishing IVCTT was 100 %. The body weight loss and cachexia of rabbits in group C appeared earlier than in group T. Body weight in the third week, the mean survival time, PI, AI in groups T and C were 2.23 {+-} 0.12 kg, 57.83 {+-} 8.68 days, (16.73 {+-} 5.18 %), (29.47 {+-} 7.18 %), and 2.03 {+-} 0.13 kg, 43.67 {+-} 5.28 days, (63.01 {+-} 2.01 %), (6.02 {+-} 2.93 %), respectively. There were statistically significant differences between group T and group C (P < 0.05). The IVCTT volume of group T was remarkably smaller than that of group C. Conclusions: Injecting and suspensory fixing VX2 tumor strip into IVC is a reliable method to establish IVCTT animal model. The linear Iodine-125 seeds strand brachytherapy was a safe and effective method for treating IVCTT

  15. Antithrombotic and Antiatherosclerotic Properties of Olive Oil and Olive Pomace Polar Extracts in Rabbits

    PubMed Central

    Tsantila, Nektaria; Karantonis, Haralabos C.; Perrea, Despina N.; Theocharis, Stamatios E.; Iliopoulos, Dimitrios G.; Antonopoulou, Smaragdi; Demopoulos, Constantinos A.

    2007-01-01

    Olive oil polar lipid (OOPL) extract has been reported to inhibit atherosclerosis development on rabbits. Olive pomace polar lipid (PPL) extract inhibits PAF activity in vitro and the most potent antagonist has been identified as a glycerylether-sn-2-acetyl glycolipid with common structural characteristics with the respective potent antagonist of OOPL. The aim of this study was to investigate the effect of PPL on early atherosclerosis development on rabbits and to compare it with the antiatherosclerotic effect of OOPL. OOPL and PPL inhibition potency, towards both PAF action and PAF binding, was tested in vitro on washed rabbit platelets. Consequently, rabbits were divided into three groups (A, B, and C). All groups were fed atherogenic diet for 22 days. Atherogenic diets in groups B and C were enriched with OOPL and PPL, respectively. At the end of the experimental time, rabbits were euthanized and aortic samples were examined histopathologically. OOPL and PPL inhibited PAF-induced aggregation, as well as specific PAF binding, with PPL being more potent. Free and bound PAF levels and PAF-AH activity were significantly elevated at the end of the experimental time. Plasma total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides levels were also found increased. Groups B and C exhibited significantly increased values of EC50 compared to group A. Histopathological examination revealed that the development of early atherosclerosis lesions in groups B and C were significantly inhibited compared to group A. Significant differences were noted in the early atherosclerosis lesions between groups B and C, thus indicating that PPL exhibit its anti-atherosclerotic activity by blocking PAF receptor. Specific PAF antagonists with similar in vitro and in vivo bioactivity to those that have been previously reported in OOPL exist in PPL. PMID:18253466

  16. Expression of IL-1β, IL-2, IL-10, TNF-β and GM-CSF in peripheral blood leukocytes of rabbits experimentally infected with rabbit haemorrhagic disease virus.

    PubMed

    Trzeciak-Ryczek, Alicja; Tokarz-Deptuła, Beata; Deptuła, Wiesław

    2016-04-15

    Rabbit haemorrhagic disease (RHD) is a highly morbid and mortal viral infection of European rabbits. This disease is one of the main causes of death in wild rabbits, and results in large economic losses in farms of rabbits worldwide. Although the first outbreak of this disease was noted in 1984, the pathogenesis of RHD and mechanisms of RHDV (rabbit haemorrhagic disease virus) pathogenecity have still not been fully elucidated. Recent studies indicate a role of the immune response, especially peripheral blood leukocytes (PBL), in the pathogenesis of this disease. Thus, in the present study we investigated the expression of IL-1β, IL-2, IL-10, TNF-β and GM-CSF genes in PBL of RHDV-infected rabbits. We also compared the expression of genes encoding these cytokines in rabbits with different course of RHDV infection (in animals that died 36h postinfection or survived until 60th h after infection). The study revealed that three (IL-10, TNF-β and GM-CSF) out of five investigated genes encoding cytokines showed increased expression in PBL of RHDV-infected rabbits, and the level of expression depended on the course of RHD. The results indicate the potential role of these cytokines in RHDV infection and their influence on the survival time of infected rabbits.

  17. The Reconstruction of Nasal Septal Perforation with High Density Porous Polyethylene Covered with Fascia Lata: An Experimental Study on Rabbit Model

    PubMed Central

    Onar, Vedat; Sayin, Ibrahim; Onol, Suzan Deniz; Aydin, Tamer

    2011-01-01

    Objectives Evaluation of a new material, high-density porous polyethylene (HDPP), which is covered with fascia lata, for experimental nasal septal perforation closure. Methods Twenty New Zealand albino rabbits were included and divided into study and control groups. A lateral incision was made from the lateral aspect of the left nares to the incisura nasomaxillaris. After exposure of the cavum nasi, the nasal mucoperichondrium was elevated bilaterally. A full-thickness 0.5×0.5-cm perforation was created over the septum nasi with a No. 11 surgical blade. A fascia lata graft was used for the study group. The HDPP was covered with fascia lata and placed under the elevated mucosa. HDPP without a fascial covering was used in the control group. Four months after the procedure, magnetic resonance imaging was performed to evaluate resorption of the material. The animals were sacrificed, and the nasal septum was completely removed. Macroscopic and histopathological examinations were performed on the nasal septum. Results All rabbits had survived after the 4-month period. Macroscopically, nine of 10 (90%) perforations were closed in the fascia lata-covered HDPP group. Histopathological examination of these nine rabbits revealed that the continuity of cartilage was disturbed in the perforation areas. Granulation tissue was inverted in areas in which the cartilage continuity was disturbed. The HDPP had remained intact at the edge of the perforation. In the HDPP group, six of 10 implants were still perforated (60%) and four (40%) were closed. The fascia lata-covered HDPP implant had a significantly higher perforation closure rate than that of the HDPP implant alone (P<0.05). Conclusion In cases of septal perforation, it is better to cover the HDPP implant with fascia lata. This covered implant can be used for the repair of nasal septal perforations. HDPP implants are easy to work with and avoid the increased operative time and morbidity associated with harvesting autografts

  18. Comparison of 1% cyclosporine eye drops in olive oil and in linseed oil to treat experimentally-induced keratoconjunctivitis sicca in rabbits.

    PubMed

    Parrilha, Leticia Rodrigues; Nai, Gisele Alborghetti; Giuffrida, Rogério; Barbero, Rafael Cabral; Padovani, Leticia Dias Fabris; Pereira, Ricardo Henrique Zaquir; Silva, Danielle Alves; Silva, Mariele Catherine Alves; Diniz, Miriely Stein; Andrade, Silvia Franco

    2015-01-01

    To evaluate the effectiveness of topical 1% cyclosporine eye drops diluted in either of the two vehicles-olive and linseed oil-and that of the oils themselves in treating experimentally-induced keratoconjunctivitis sicca (KCS) in rabbits. KCS was induced in 25 New Zealand rabbits using 1% atropine sulfate eye drops for 7 days before treatment and throughout the treatment period (12 weeks). The rabbits were divided into five groups: one control (C) group without KCS induction and four treatment groups in which KCS was induced and treated topically with olive oil (O), linseed oil (L), cyclosporine in olive oil (CO), and cyclosporine in linseed oil (CL). The animals were evaluated using Schirmer tear test 1 (STT), the fluorescein test (FT), tear-film break-up time (TBUT), the rose bengal test (RBT), and histopathological analysis. Values of STT and TBUT significantly decreased 1 week post-induction (p<0.05) and were similar to initial values after the 4th week of treatment, in all groups. After KCS induction, there was significantly less corneal damage in group L than in group CL, as assessed FT and RBT. Histopathology demonstrated that Groups L and CL presented less edema and corneal congestion. There was no significant difference in the goblet cell density (cells/mm2) between the groups (p=0.147). Cyclosporine diluted in olive oil or linseed oil was effective in the treatment of KCS, although it had better efficacy when diluted in linseed oil. Linseed oil presented better effectiveness, whether associated or not, than olive oil. These results may contribute to the creation of novel topical ophthalmic formulations for KCS treatment in future.

  19. Ezetimibe reduces plaque inflammation in a rabbit model of atherosclerosis and inhibits monocyte migration in addition to its lipid-lowering effect

    PubMed Central

    Gómez-Garre, D; Muñoz-Pacheco, P; González-Rubio, ML; Aragoncillo, P; Granados, R; Fernández-Cruz, A

    2009-01-01

    Background and purpose: Ezetimibe, a selective inhibitor of intestinal cholesterol absorption, might also suppress inflammatory components of atherogenesis. We have studied the effects of ezetimibe on two characteristics of atherosclerotic plaques (infiltrate and fibrosis) and on expression of inflammatory genes in a rabbit model of accelerated atherosclerosis. Experimental approach: Femoral atherosclerosis was induced by a combination of endothelial desiccation and atherogenic diet. Animals were randomized to ezetimibe (0.6 mg·kg−1·day−1), simvastatin (5 mg·kg−1·day−1), ezetimibe plus simvastatin or no treatment, still on atherogenic diet. A control group of rabbits received normolipidemic diet. Key results: Rabbits fed the normolipidemic diet showed normal plasma lipid levels. Either the normolipidemic diet or drug treatment reduced the intima/media ratio (normolipidemic diet: 22%, ezetimibe: 13%, simvastatin: 27%, ezetimibe + simvastatin: 28%), compared with rabbits with atherosclerosis. Ezetimibe also decreased macrophage content and monocyte chemoattractant protein-1 expression in atherosclerotic lesions. Furthermore, ezetimibe reduced the increased activity of nuclear factor κB in peripheral blood leucocytes and plasma C-reactive protein levels in rabbits with atherosclerosis. In THP-1 cells, ezetimibe decreased monocyte chemoattractant protein-1-induced monocyte migration. Importantly, the combination of ezetimibe with simvastatin was associated with a more significant reduction in plaque monocyte/macrophage content and some proinflammatory markers than observed with each drug alone. Conclusions and implications: Ezetimibe had beneficial effects both on atherosclerosis progression and plaque stabilization and showed additional anti-atherogenic benefits when combined with simvastatin. Its effect on monocyte migration provides a potentially beneficial action, in addition to its effects on lipids. PMID:19222481

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

    PubMed Central

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

    2014-01-01

    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. PMID:25277507

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

    PubMed

    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.

  2. [Quantitative analysis of lesions of the aortic and carotid artery endothelium in experimental diabetes in rabbits by scanning electron microscopy].

    PubMed

    Dolgov, V V; Zaikina, O E; Bondarenko, M F; Repin, V S

    1981-01-01

    A significant increase in the number and zone area of argyrophil cells, craters and stomata of the intracellular formations were seen in the aortic and carotid pectoral and peritoneal regions of rabbits with 5-week alloxan diabetes. The number and zone area of vascular de-endothelization did not increase. Cell polymorphism, apart from maintenance of pronounced argyrophilia and micro-injuries, occurred to diabetes of 5-month standing. Deranged properties of the macrovascular endothelial integument may be of great importance in the pathogenesis of atheromatosis in diabetes mellitus.

  3. [Morphometric measurements in the area of the epiphyseal groove of the parietal vertebra in experimentally-induced scoliosis in rabbits].

    PubMed

    Kneer, W; Mitzkat, K

    1986-01-01

    In 3 rabbits we provoked a short-curved dorsolumbal scoliosis by costo-lumbal cerclage. In order to quantify with morphometric methods the morphologically by various authors described effect of pressure parallel to the axis of epiphyseal growth under Hueter-Volkmann's law, we measured the height and area of different parts of the epiphyseal plate in frontal semi-thin sections (Alcian-blue) by means of a pictoral analysis system based on a mini-computer. On the concave side, the side of increased pressure, we found a relative atrophy of the epiphyseal plate of 40% and a diminished area of 49%.

  4. [Comparative analysis between sclera treated with glycerin and sclera treated with gamma irradiation, alkali and glycerin in the reconstruction of anophthalmic socket: experimental study in rabbits].

    PubMed

    Fernandes, José Byron Vicente Dias; Matayoshi, Suzana; Osaka, Junko Takano; Tolosa, Erasmo Castro Magalhães; Nunes, Tânia Pereira; Moura, Eurípedes da Mota

    2007-01-01

    To compare two sclera decontamination methods: treatment with glycerin versus treatment with gamma irradiation, alkali and glycerin, aiming to detect the clinical and histological alterations in rabbit anophthalmic sockets reconstructed with sclera-involved polymethylmethacrylate spheres. Thirty-nine New Zealand-breed rabbits were divided into two groups: group I, whose animals were submitted to enucleation of one eye and reconstruction with a polymethylmethacrylate sphere involved in glycerin-treated sclera; group II, where there was enucleation, and reconstruction performed with a polymethylmethacrylate sphere involved in sclera treated with gamma irradiation, alkali and glycerin. The two groups were observed at four moments, at 7, 21, 42 and 84 days after surgery. Preset times elapsed, the rabbits were euthanized, sockets were exenterated, the material was processed for embedment in paraffin, cut into 5 microm sections thick and stained with hematoxylin-eosin and Masson's trichrome techniques. The scleras were submitted to morphometric and semiquantitative analysis. Results were compared by Mann-Whitney's non-parametric test. Comparative analysis of vascularization of the surgical interface pointed out a significative difference in the evaluation done 21 days after the implant (P<0.001), with group II showing greater neovascularization. Comparison of the fibrous capsule thickness displayed a significative difference at moments corresponding to 21 days (P<0.001) and 42 days (P<0.001). At both moments, group II presented a thicker fibrous capsule than group I. Likewise, there was variation in sclera thickness, being thicker in group II, at the 21-day post-implant (P=0.003) moment, and at the 42-day moment (P=0.024), as well. Along the experimental period, when groups were analyzed we could observe statistically significative diminution of vascularization in the surgical interface, in group I, as well as in group II, at the moment of 7, 21, 42 and 84 days. When

  5. Morphological features of coronary plaques in WHHLMI rabbits (Oryctolagus cuniculus), an animal model for familial hypercholesterolemia

    PubMed Central

    Yamada, Satoshi; Koike, Tomonari; Nakagawa, Takayuki; Kuniyoshi, Nobue; Ying, Yu; Itabe, Hiroyuki; Yamashita, Atsushi; Asada, Yuji; Shiomi, Masashi

    2016-01-01

    In order to examine their suitability for studies on coronary atherosclerosis, we evaluated the features of coronary atherosclerotic plaques in myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits, a spontaneous animal model for coronary atherosclerosis and myocardial infarction. Coronary segments of the hearts of 187 WHHLMI rabbits (10–29 months old) were sectioned serially and stained histopathologically and immunohistologically. Progression of coronary lesions was prominent in rabbits that had died suddenly. The degree of coronary lesions of females was higher than that of males. Various types of atherosclerotic lesions were observed in the coronary arteries, such as plaques with a large lipid core covered by a thin fibrous cap, fatty streaks, early and advanced fibroatheromas, fibrous lesions, and advanced lesions with calcium accumulation and the vasa vasorum. In rabbits that had died suddenly, the frequencies of fibroatheromas or advanced lesions were higher than those of rabbits euthanized. Matrix metalloproteinase (MMP)-positive macrophages were detected in gaps among endothelial cells at the plaque surface, beneath the fibrous cap of thin-capped fibroatheromas, and at the bottom of the intimal plaques in which the tunica media was attenuated. Immunohistological results suggest that MMP-positive macrophages are involved in the initiation, progression, and destabilization of coronary plaques, in addition to vascular remodeling, even in WHHLMI rabbits. In conclusion, coronary lesions in WHHLMI rabbits resemble human atherosclerotic lesions, and thus, the WHHLMI rabbit is a suitable animal model for studies on human coronary plaques. PMID:28025424

  6. Morphological features of coronary plaques in WHHLMI rabbits (Oryctolagus cuniculus), an animal model for familial hypercholesterolemia.

    PubMed

    Yamada, Satoshi; Koike, Tomonari; Nakagawa, Takayuki; Kuniyoshi, Nobue; Ying, Yu; Itabe, Hiroyuki; Yamashita, Atsushi; Asada, Yuji; Shiomi, Masashi

    2017-05-03

    In order to examine their suitability for studies on coronary atherosclerosis, we evaluated the features of coronary atherosclerotic plaques in myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits, a spontaneous animal model for coronary atherosclerosis and myocardial infarction. Coronary segments of the hearts of 187 WHHLMI rabbits (10-29 months old) were sectioned serially and stained histopathologically and immunohistologically. Progression of coronary lesions was prominent in rabbits that had died suddenly. The degree of coronary lesions of females was higher than that of males. Various types of atherosclerotic lesions were observed in the coronary arteries, such as plaques with a large lipid core covered by a thin fibrous cap, fatty streaks, early and advanced fibroatheromas, fibrous lesions, and advanced lesions with calcium accumulation and the vasa vasorum. In rabbits that had died suddenly, the frequencies of fibroatheromas or advanced lesions were higher than those of rabbits euthanized. Matrix metalloproteinase (MMP)-positive macrophages were detected in gaps among endothelial cells at the plaque surface, beneath the fibrous cap of thin-capped fibroatheromas, and at the bottom of the intimal plaques in which the tunica media was attenuated. Immunohistological results suggest that MMP-positive macrophages are involved in the initiation, progression, and destabilization of coronary plaques, in addition to vascular remodeling, even in WHHLMI rabbits. In conclusion, coronary lesions in WHHLMI rabbits resemble human atherosclerotic lesions, and thus, the WHHLMI rabbit is a suitable animal model for studies on human coronary plaques.

  7. Expression of NF-E2-related factor 2 (Nrf2) in the basilar artery after experimental subarachnoid hemorrhage in rabbits: a preliminary study.

    PubMed

    Zhao, Xu-Dong; Zhou, Yi-Ting; Zhang, Xing; Wang, Xiao-Liang; Qi, Wu; Zhuang, Zong; Su, Xing-Fen; Shi, Ji-Xin

    2010-10-28

    It has been suggested that the pathogenesis of vasospasm is complex including endothelial damage, oxidative stress, inflammatory damage, and the accumulation of toxic metabolites. Recently, a growing body of evidence indicates that nuclear factor erythroid 2-related factor 2 (Nrf2) plays a unique role in many physiological stress processes. In this study, a total of 48 rabbits were assigned randomly to four groups: control group, SAH day 3, day 5, and day 7 groups. The animals in SAH day 3, day 5, and day 7 groups were subjected to injection of autologous blood into cisterna magna twice on day 0 and day 2 and were killed on days 3, 5, and 7, respectively. Cross-sectional area of basilar artery was measured and the Nrf2 expression was assessed by immunohistochemistry and Western blot analysis. The mRNA levels of Nrf2 were also determined by RT-PCR. The basilar arteries exhibited vasospasm after SAH and became more severe on days 3 and 5. The elevated expression of Nrf2 was detected after SAH and peaked on days 3 and 5. Nrf2 is increasingly expressed in a parallel time course to the development of cerebral vasospasm in a rabbit experimental model of SAH.

  8. Experimental syringohydromyelia induced by adhesive arachnoiditis in the rabbit: changes in the blood-spinal cord barrier, neuroinflammatory foci, and syrinx formation.

    PubMed

    Kobayashi, Shigeru; Kato, Katsura; Rodríguez Guerrero, Alexander; Baba, Hisatoshi; Yoshizawa, Hidezo

    2012-06-10

    There are many histological examinations of syringohydromyelia in the literature. However, there has been very little experimental work on blood permeability in the spinal cord vessels and ultrastructural changes. We prepared an animal model of spinal adhesive arachnoiditis by injecting kaolin into the subarachnoid space at the eighth thoracic vertebra of rabbits. The animals were evaluated 4 months later. Of the 30 rabbits given kaolin injection into the cerebrospinal fluid, 23 showed complete circumferential obstruction. In the 7 animals with partial obstruction of the subarachnoid space, intramedullary changes were not observed. However, among the 23 animals showing complete obstruction of the subarachnoid space, dilatation of the central canal (hydromyelia) occurred in 21, and intramedullary syrinx (syringomyelia) was observed in 11. In animals with complete obstruction, fluorescence microscopy revealed intramedullary edema around the central canal, extending to the posterior columns. Electron microscopy of hydromyelia revealed a marked reduction of villi on the ependymal cells, separation of the ependymal cells, and cavitation of the subependymal layer. The dilated perivascular spaces indicate alterations of fluid exchange between the subarachnoid and extracellular spaces. Syringomyelia revealed that nerve fibers and nerve cells were exposed on the surface of the syrinx, and necrotic tissue was removed by macrophages to leave a syrinx. Both pathologies differ in their mechanism of development: hydromyelia is attributed to disturbed reflux of cerebrospinal fluid, while tissue necrosis due to disturbed intramedullary blood flow is considered to be involved in formation of the syrinx in syringomyelia.

  9. Histological evaluation of Accell Connexus(®) and Bio-Oss(®) on quality and rate of bone healing: a single blind experimental study on rabbit's calvarium.

    PubMed

    Khorsand, A; Rasouli Ghahroudi, A A R; Motahhari, P; Rezaei Rad, M; Soleimani Shayesteh, Y

    2012-01-01

    The objective of this study was to evaluate the effect of Accell Connexus(®) on the quality and rate of healing in experimental defects of rabbit calvarium compared to Bio-Oss®. Twelve 2.5-3.5 kg weighing New Zealand white rabbits were used. Three defects (3×6 mm) were created in the cranium of the animals subsequently filled with Accell Connexus(®), Bio-Oss® or served as controls. The animals were sacrificed four, six and eight weeks postoperatively and the histology blocks were studied in terms of inflammation, trabeculation thickness, bone type regeneration, foreign body and remained biomaterial by light microscope. The data were subject to Mann-Whitney U test. Increased inflammatory reaction, foreign body reaction, delayed bone formation and lower rate of ossification were observed in DBM-filled defects compared to Bio-Oss® or controls. However, no significant differences were observed in bone formation between Bio-Oss®, Accell Connexus(®) and control specimens in the three time intervals. Furthermore, no significant differences were noted between Bio-Oss® and control groups. Accell Connexus(®) showeda lower rate of ossification and bone healing compared to Bio-Oss® or controlgroups. Other studies in this field seem necessary.

  10. The effects of early or late treatment of osteochondral defects on joint homoeostasis: an experimental study in rabbits.

    PubMed

    Ozsoy, Mehmet Hakan; Aydogdu, Semih; Taskiran, Dilek; Sezak, Murat; Hayran, Mutlu; Oztop, Fikri; Ozsoy, Arzu

    2009-06-01

    A 3.5 x 4 mm tubular osteochondral defect was created on the right medial femoral condyles of 51 adult rabbits. In the control group (CG), defects were left untreated. In the early-(ETG) and late-(LTG) treatment groups, defects were treated by an osteoperiosteal graft 1 and 12 weeks, respectively, after the index procedure. Synovial fluid (SF) samples were collected regularly and proteoglycan fragments (PF), total collagen (TC) and collagenase (MMP-1) levels were measured. Rabbits were killed at 4 (early period), 12 (intermediate period), or 24 (late period) weeks postoperatively. Histological examination indicated a more successful healing in both grafting groups than in the CG, but without any difference at any time period between the grafting groups. In the CG, PF, and TC levels in SF increased continuously until the late period, indicating an ongoing degenerative activity in the joints. In contrast, SF marker levels in both grafting groups indicated that normalization in joint metabolism could be achieved-at least partially-after treatment. However, PF levels in the SF showed that the treatment of defects in earlier stages might result in better outcomes since the negative effects were more prominent in chronic stages, presumably due to the more prolonged period of disturbed homeostasis. Thus, histological values and SF marker levels indicated that treatment of osteochondral defects at any time of the disease had a positive effect on healing when compared to no treatment. Early treatment might better assist the recovery of joint homeostasis than late treatment.

  11. Influence of material and microtopography on the development of local infection in vivo: experimental investigation in rabbits.

    PubMed

    Moriarty, Thomas F; Debefve, Laurence; Boure, Ludovic; Campoccia, Davide; Schlegel, Urs; Richards, Robert G

    2009-09-01

    Polishing the surface of internal fracture fixation (IFF) implant materials can ease implant removal and reduce irritation to gliding tissues by reducing soft tissue adhesion and bony overgrowth. Thus, polishing the surface of these implants is expected to have significant clinical benefit in certain situations. The aim of the present study was to determine if polishing the surface of an IFF device influences susceptibility to infection. The local infection rate associated with 4-hole 2.0 mm Synthes locking compression plates (LCPs) composed of clinically available commercially pure titanium (cpTi) and titanium aluminium niobium (TAN) in their standard microrough form was compared with that of their test polished equivalents and also to clinically available electropolished stainless steel (EPSS). The LCPs were fixed in locking mode onto the tibia of mature, female New Zealand White rabbits and a clinical strain of Staphylococcus aureus was added to the implantation site. Twenty eight days after surgery the rabbits were euthanized and assessed for infection. The rank order based on descending ID50 was; polished TAN, standard TAN, standard cpTi, EPSS and finally polished cpTi, however, the ID50 values did not differ greatly between the groups with the same material. Using the LCP model in locking mode, polishing the surface of both cpTi and TAN was not found to influence the susceptibility to infection in our animal model.

  12. Experimental infection of specific pathogen-free New Zealand White rabbits with five strains of amyxomatous myxoma virus.

    PubMed

    Marlier, D; Cassart, D; Boucraut-Baralon, C; Coignoul, F; Vindevogel, H

    1999-11-01

    Myxomatosis is a specific disease of the European rabbit (Oryctolagus cuniculus) due to a virus belonging to the genus Leporipoxvirus. Forty-seven years after its deliberate introduction into Europe, the clinical aspects and the epizootiology of myxomatosis have changed. Two forms (nodular and amyxomatous) of the disease have been identified to date. A comparative study was made of the clinical signs, pathogenesis and gross lesions observed in male specific pathogen-free New Zealand White rabbits inoculated with five strains of amyxomatous myxoma virus. All five strains induced the characteristic amyxomatous myxomatosis clinical syndrome with clinical signs that differed only in intensity. The varying clinical intensity, together with the results of virological examination question the virulence of at least three of the five strains. Genomic analysis confirmed that the five strains came from the Lausanne strain introduced in 1952 in France and not from an unnoticed introduction of a Californian strain of myxoma virus. No link was found between the amyxomatous myxoma virus strains and the SG33 vaccine strain. 1999 Harcourt Publishers Ltd.

  13. [Experimental study of ectopic bone formation of engineered bone constructs under the periosteum of New-Zealand rabbits].

    PubMed

    Zhou, Qiang; Wang, Yang; Yu, Jie; Yu, Ying-hao

    2011-10-01

    To study the feasibility of ectopic bone formation for engineered bone constructs with bone marrow stromal cells (BMSCs). BMSCs were obtained from 3-month female New-Zealand rabbits with weight of 3 kg, induced to osteogenitor cell, were expanded by culture and then seeded into the porous beta-tricalcium phosphate (beta-TCP) particles. Engineered bone constructs were implanted under the periostem of rabbit femur. Samples were retrieved and examed after 3 months. Blood vessels and osteoblast were examined through optical microscope. Twelve implanted engineered bone particles of 16 samples were fixed well under periosteum and rounded by periosteum. There were a lot of vessels and new bone in engineered bone. The structure of bone was disorder; the vessels arranged equally. Four cases found implanted bone freed outside of periosteum,lots of implanted material were absorbed,the volume of residual was less than osteogenesis, and lack of blood vessel. 80% engineered bone constructs attached to the femur under the periostem very well,osteogenesis was fine and vessels were growed into new bone. Engineered bone can obtained good ectopic bone under the periostem.

  14. The repair of critical-size defects with porous hydroxyapatite/polyamide nanocomposite: an experimental study in rabbit mandibles.

    PubMed

    Zhang, J C; Lu, H Y; Lv, G Y; Mo, A C; Yan, Y G; Huang, C

    2010-05-01

    This study was conducted to evaluate the healing of critical-size surgical defects after implantation of porous nano-hydroxyapatite/polyamide composite (nHA/PA) blocks based on a bilateral mandible model using adult New Zealand white rabbits. 15 rabbits were divided randomly into three groups according to the observation period: 4, 12 and 24 weeks. The defects on one side were implanted with nHA/PA blocks and the contralateral defects were kept empty as blank controls. A combination of macroscopic, radiographic, histological and histomorphometric studies were performed up to 24 weeks postoperatively and compared with normal healing. Large amounts of callus and active osteoblasts were found in the pore structure after 4 weeks of implantation, and the defects were completely occupied by neo-bone with density comparable with that of host bone at 24 weeks. Significant difference was found between nHA/PA groups and blank controls regarding X-ray opacity over the whole period and bone parameters at 4 weeks postoperation (P<0.05). The porous nHA/PA composite promotes bone formation over the extension of the defect, particularly in the early stage. Porous nHA/PA offers interesting potential for maxillofacial reconstructive procedures in load-free areas. Copyright 2010 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  15. Lipid and protein maps defining arterial layers in atherosclerotic aorta

    PubMed Central

    Martin-Lorenzo, Marta; Balluff, Benjamin; Maroto, Aroa S.; Carreira, Ricardo J.; van Zeijl, Rene J.M.; Gonzalez-Calero, Laura; de la Cuesta, Fernando; Barderas, Maria G; Lopez-Almodovar, Luis F; Padial, Luis R; McDonnell, Liam A.; Vivanco, Fernando; Alvarez-Llamas, Gloria

    2015-01-01

    Subclinical atherosclerosis cannot be predicted and novel therapeutic targets are needed. The molecular anatomy of healthy and atherosclerotic tissue is pursued to identify ongoing molecular changes in atherosclerosis development. Mass Spectrometry Imaging (MSI) accounts with the unique advantage of analyzing proteins and metabolites (lipids) while preserving their original localization; thus two dimensional maps can be obtained. Main molecular alterations were investigated in a rabbit model in response to early development of atherosclerosis. Aortic arterial layers (intima and media) and calcified regions were investigated in detail by MALDI-MSI and proteins and lipids specifically defining those areas of interest were identified. These data further complement main findings previously published in J Proteomics (M. Martin-Lorenzo et al., J. Proteomics. (In press); M. Martin-Lorenzo et al., J. Proteomics 108 (2014) 465–468.) [1,2]. PMID:26217810

  16. Noninvasive imaging of focal atherosclerotic lesions using fluorescence molecular tomography

    NASA Astrophysics Data System (ADS)

    Maji, Dolonchampa; Solomon, Metasebya; Nguyen, Annie; Pierce, Richard A.; Woodard, Pamela K.; Akers, Walter J.; Achilefu, Samuel; Culver, Joseph P.; Abendschein, Dana R.; Shokeen, Monica

    2014-11-01

    Insights into the etiology of stroke and myocardial infarction suggest that rupture of unstable atherosclerotic plaque is the precipitating event. Clinicians lack tools to detect lesion instability early enough to intervene, and are often left to manage patients empirically, or worse, after plaque rupture. Noninvasive imaging of the molecular events signaling prerupture plaque progression has the potential to reduce the morbidity and mortality associated with myocardial infarction and stroke by allowing early intervention. Here, we demonstrate proof-of-principle in vivo molecular imaging of C-type natriuretic peptide receptor in focal atherosclerotic lesions in the femoral arteries of New Zealand white rabbits using a custom built fiber-based, fluorescence molecular tomography (FMT) system. Longitudinal imaging showed changes in the fluorescence signal intensity as the plaque progressed in the air-desiccated vessel compared to the uninjured vessel, which was validated by ex vivo tissue studies. In summary, we demonstrate the potential of FMT for noninvasive detection of molecular events leading to unstable lesions heralding plaque rupture.

  17. Trace elemental distributions in induced atherosclerotic lesions using nuclear microscopy

    NASA Astrophysics Data System (ADS)

    Minqin, Ren; Watt, Frank; Tan Kwong Huat, Benny; Halliwell, B.

    2003-09-01

    Nuclear Microscopy, using the combination of scanning transmission ion microscopy, Rutherford backscattering spectrometry and proton induced X-ray emission has the ability to map and accurately quantify localised trace element levels in newly formed atherosclerotic lesions. In this study, New Zealand white rabbits fed on a high cholesterol diet were divided into two groups. One test group was treated with an iron chelating agent desferal, and the second group served as a control model. Tissue sections were taken from the aortic arch, flash frozen and air-dried, and scanned using the nuclear microscope of the Research Centre for Nuclear Microscopy, NUS. Results of this experiment, although not definitive ( p=0.07) indicated that during the treatment with desferal, there was a trend for lesion development to be slowed down. However, analysis of atherosclerotic lesions both from the test and control groups showed that iron concentrations within the lesions exhibit a high degree of correlation with the depth of the lesion in the artery wall, whereas zinc is observed to be anti-correlated to the size of the lesion area. This investigation implies that the observed high iron levels, which can lead to increased free radical damage, may cause premature or accelerated arterial damage.

  18. Photosensitizer delivery to vulnerable atherosclerotic plaque: comparison of macrophage-targeted conjugate versus free chlorin(e6).

    PubMed

    Tawakol, Ahmed; Castano, Ana P; Anatelli, Florencia; Bashian, Gregory; Stern, Jeremy; Zahra, Touqir; Gad, Faten; Chirico, Stephanie; Ahmadi, Atosa; Fischman, Alan J; Muller, James E; Hamblin, Michael R

    2006-01-01

    We have previously shown that a conjugate (MA-ce6) between maleylated serum albumin and the photosensitizer chlorin(e6) (ce6) is targeted in vitro to macrophages via class A scavenger receptors. We now report on the ability of this conjugate to localize in macrophage-rich atherosclerotic plaques in vivo. Both the conjugate and the free photosensitizer ce6 are studied after injection into New Zealand White rabbits that are rendered atherosclerotic by a combination of aortic endothelial injury and cholesterol feeding into normal rabbits. Rabbits are sacrificed at 6 and 24 h after injection and intravascular fluorescence spectroscopy is carried out by fiber-based fluorimetry in intact blood-filled arteries. Surface spectrofluorimetry of numbered excised aortic segments together with injured and normal iliac arteries is carried out, and quantified ce6 content by subsequent extraction and quantitative fluorescence determination of the arterial segments and also of nontarget organs. There is good agreement between the various techniques for quantifying ce6 localization, and high contrast between arteries from atherosclerotic and normal rabbits is obtained. Fluorescence correlates with the highest burden of plaque in the aorta and the injured iliac artery. The highest accumulation in plaques is obtained using MA-ce6 at 24 h. Free ce6 gives better accumulation at 6 h compared to 24 h. The liver, spleen, lung, and gall bladder have the highest uptake in nontarget organs. Macrophage-targeted photosensitizer conjugates may have applications in both detecting and treating inflamed vulnerable plaque.

  19. Photosensitizer delivery to vulnerable atherosclerotic plaque: comparison of macrophage-targeted conjugate versus free chlorine(e6)

    NASA Astrophysics Data System (ADS)

    Tawakol, Ahmed; Castano, Ana P.; Anatelli, Florencia; Bashian, Gregory; Stern, Jeremy; Zahra, Touqir; Gad, Faten; Chirico, Stephanie; Ahmadi, Atosa; Fischman, Alan J.; Muller, James E.; Hamblin, Michael R.

    2006-03-01

    We have previously shown that a conjugate (MA-ce6) between maleylated serum albumin and the photosensitizer chlorin(e6) (ce6) is targeted in vitro to macrophages via class A scavenger receptors. We now report on the ability of this conjugate to localize in macrophage-rich atherosclerotic plaques in vivo. Both the conjugate and the free photosensitizer ce6 are studied after injection into New Zealand White rabbits that are rendered atherosclerotic by a combination of aortic endothelial injury and cholesterol feeding into normal rabbits. Rabbits are sacrificed at 6 and 24 h after injection and intravascular fluorescence spectroscopy is carried out by fiber-based fluorimetry in intact blood-filled arteries. Surface spectrofluorimetry of numbered excised aortic segments together with injured and normal iliac arteries is carried out, and quantified ce6 content by subsequent extraction and quantitative fluorescence determination of the arterial segments and also of nontarget organs. There is good agreement between the various techniques for quantifying ce6 localization, and high contrast between arteries from atherosclerotic and normal rabbits is obtained. Fluorescence correlates with the highest burden of plaque in the aorta and the injured iliac artery. The highest accumulation in plaques is obtained using MA-ce6 at 24 h. Free ce6 gives better accumulation at 6 h compared to 24 h. The liver, spleen, lung, and gall bladder have the highest uptake in nontarget organs. Macrophage-targeted photosensitizer conjugates may have applications in both detecting and treating inflamed vulnerable plaque.

  20. Neovascularization and tumor growth in the rabbit brain. A model for experimental studies of angiogenesis and the blood-brain barrier.

    PubMed Central

    Zagzag, D.; Brem, S.; Robert, F.

    1988-01-01

    A model for the study of tumor angiogenesis within the rabbit brain is presented. Implantation of the VX2 carcinoma provides a reproducible tumor accompanied by angiogenesis. The authors report the sequential growth, histology, tumor neovascularization, and vascular permeability of this tumor following its intracerebral implantation. Tumor angiogenesis correlates with the rapid and logarithmic intracerebral tumor growth. The proliferation of blood vessels in the tumor and the organization of tumor cells around tumor vessels are described. Breakdown of the blood-brain barrier (detected by Evans blue leakage) starts in the early stages of tumor development and becomes prominent as the tumor vasculature and size increase. This model is useful for experimental studies of angiogenesis. Images Figure 2 Figure 3 Figure 6 Figure 4 Figure 5 Figure 7 Figure 8 Figure 10 Figure 12 Figure 13 Figure 15 PMID:2451889

  1. Experimental Design and Surgical Approach to Create a Spinal Fusion Model in a New Zealand White Rabbit (Oryctolagus cuniculus).

    PubMed

    Virk, Sohrab S; Coble, Dondrae; Bertone, Alicia L; Hussein, Hayam Hamaz; Khan, Safdar N

    2017-08-01

    There are several animal models routinely used for study of the spinal fusion process and animal selection largely depends on the scientific question to be answered. This review outlines the advantages and disadvantages of various animal models used to study spinal fusion and describes the New Zealand White (NSW) rabbit which is the most popular preclinical model to study spinal fusion. We outline critical steps required in planning and performing spinal fusion surgery in this model. This includes determination of the required animal number to obtain statistical significance, an outline of appropriate technique for posterolateral fusion and other components of completing a study. As advances in drug delivery move forward and our understanding of the cascade of gene expression occurring during the fusion process grows, performing and interpreting preclinical animal models will be vital to validating new therapies to enhance spinal fusion.

  2. [Quantitative study of experimental osteoarthritic lesions in the rabbit. Value for the study of anti-osteoarthritis drugs].

    PubMed

    Vignon, E; Bejui, J; Hartmann, D J; Ville, G; Vial, B; Mathieu, P

    1986-11-01

    Section of the anterior cruciate ligament of the right knee was performed in 20 rabbits which were sacrificed 3 months later. During that time, 10 animals were treated with a proteino-polysaccharide compound. The importance of cartilage destruction was evaluated by measuring the articular surfaces and the surface of the fissured areas using an automatic image analyzer; osteophytes were measured by a volumetric study. The percentage of the fissured areas appears to be without correlation with the osteophytosis, the increase of the water content or the decrease of glycosaminoglycans following the procedure. In animals which were treated, the extent of the fissure is significantly reduced but the biochemical and histometric modifications are not too different from those of the reference group.

  3. Preparation of porous PLA/DBM composite biomaterials and experimental research of repair rabbit radius segmental bone defect.

    PubMed

    Zhang, Yumin; Wang, Jianru; Wang, Jue; Niu, Xiaojun; Liu, Jianchun; Gao, Lan; Zhai, Xiaoyan; Chu, Kaibo

    2015-12-01

    Bone substitutes are used in wide range of orthopaedic application. An ideal bone substitute should exhibit superior osteoinductive and osteoconductive properties. Neither bio-derived materials nor synthetic materials can meet the needs of an ideal bone substitute. Preparation of composite materials is a promising way to improve properties of biomaterial. In this study, the porous poly lactic acid (PLA)/demineralized bone matrix (DBM) composite biomaterials prepared by supercritical CO2 technique were implanted to repair rabbit radius segmental bone defect. By comparing with PLA and bone autograft, the X-ray result and histological analysis showed the repair effect of PLA/DBM porous composite materials is significantly better than that of the PLA group and the blank control group, and is similar to autologous bone. The PLA/DBM can promote the healing of bone defects and can be used as a kind of ideal alternative materials to repair bone defects.

  4. Bone regeneration and infiltration of an anisotropic composite scaffold: an experimental study of rabbit cranial defect repair.

    PubMed

    Li, Jidong; You, Fu; Li, Yubao; Zuo, Yi; Li, Limei; Jiang, Jiaxing; Qu, Yili; Lu, Minpeng; Man, Yi; Zou, Qin

    2016-01-01

    Tissue formation on scaffold outer edges after implantation may restrict cell infiltration and mass transfer to/from the scaffold center due to insufficient interconnectivity, leading to incidence of a necrotic core. Herein, a nano-hydroxyapatite/polyamide66 (n-HA/PA66) anisotropic scaffold with axially aligned channels was prepared with the aim to enhance pore interconnectivity. Bone tissue regeneration and infiltration inside of scaffold were assessed by rabbit cranial defect repair experiments. The amount of newly formed bone inside of anisotropic scaffold was much higher than isotropic scaffold, e.g., after 12 weeks, the new bone volume in the inner pores was greater in the anisotropic scaffolds (>50%) than the isotropic scaffolds (<30%). The results suggested that anisotropic scaffolds could accelerate the inducement of bone ingrowth into the inner pores in the non-load-bearing bone defects compared to isotropic scaffolds. Thus, anisotropic scaffolds hold promise for the application in bone tissue engineering.

  5. Flow in Atherosclerotic Blood Vessels

    NASA Astrophysics Data System (ADS)

    Berger, Stanley A.; Stroud, Jenn S.

    2000-11-01

    Atherosclerotic lesions occur in arteries where there are major changes in flow structure, e.g. bifurcations and junctions. The reduction of vessel lumen alters the flow, including the mechanical forces on the walls. We have examined the flow in carotid artery bifurcations with realistic plaque contours. The unsteady, incompressible, Navier-Stokes equations are solved in finite-volume form. Steady and pulsatile flows have been analyzed for laminar and turbulent flows, using for the latter a low-Reynolds number k- ɛ model and a k-ω model. Non-Newtonian viscosity is also considered using a power-law model. In general the very irregular contours of the vessels lead to recirculating regions, strong spatial variations of wall shear stresses, and in some cases, vortex shedding. Even steady inlet flow exhibits fluctuating, unsteady behavior. Neither turbulence models captures all the physics of the flow. The flow, in fact, appears to be transitional and not fully turbulent. For unsteady flow, there are also strong temporal variations of normal and shear stresses, which together with the strong spatial variations, has important implications for the onset and progression of atherosclerotic disease.

  6. Lysophosphatidic acid in atherosclerotic diseases

    PubMed Central

    Schober, Andreas; Siess, Wolfgang

    2012-01-01

    Lysophosphatidic acid (LPA) is a potent bioactive phospholipid. As many other biological active lipids, LPA is an autacoid: it is formed locally on demand, and it acts locally near its site of synthesis. LPA has a plethora of biological activities on blood cells (platelets, monocytes) and cells of the vessel wall (endothelial cells, smooth muscle cells, macrophages) that are all key players in atherosclerotic and atherothrombotic processes. The specific cellular actions of LPA are determined by its multifaceted molecular structures, the expression of multiple G-protein coupled LPA receptors at the cell surface and their diverse coupling to intracellular signalling pathways. Numerous studies have now shown that LPA has thrombogenic and atherogenic actions. Here, we aim to provide a comprehensive, yet concise, thoughtful and critical review of this exciting research area and to pinpoint potential pharmacological targets for inhibiting thrombogenic and atherogenic activities of LPA. We hope that the review will serve to accelerate knowledge of basic and clinical science, and to foster drug development in the field of LPA and atherosclerotic/atherothrombotic diseases. PMID:22568609

  7. Hyperspectral characterization of atherosclerotic plaques

    NASA Astrophysics Data System (ADS)

    Randeberg, Lise L.; Larsen, Eivind L. P.; Aksnes, Astrid; Haugen, Olav A.; Svaasand, Lars O.

    2009-07-01

    Imaging modalities like hyperspectral imaging create large amounts of data. Time efficient, automated analytic techniques are therefore required to enjoy the power of such methods. In this study it was investigated if hyperspectral imaging followed by automated noise filtering and statistical image analysis is a suitable method for characterization of the macroscopic structure of atherosclerotic lesions. Ten human aorta samples (6×8 cm) were collected during autopsy. Hyperspectral white light and fluorescence images and 5 - 6 biopsies were collected from each sample. The biopsies were stained (HES, Sudan red), and grouped according to histology. All images were noise filtered and normalized. Fluorescence spectra were collected from all biopsied regions, and used to compute average spectra for each histological group. Supervised classification was performed using Spectral angle mapping (SAM) with the average spectra as endmembers. K-means- and ISO-data clustering was used for unsupervised classification. The results show that noise filtering and normalization is essential for reliable classification. Supervised classification was in general found to perform better than unsupervised classification. However, the SAM results strongly depend on the variation in the spectra used to compute the average endmember spectra. The analysis show that fatty deposits, calcifications, connective tissue and hemoglobin can be identified. The lesions were found to have a complex structure where vulnerable regions could be found next to stabile regions within the same lesion. In conclusion hyperspectral imaging, automated filtering and -analysis was found to be a suitable tool to classify advanced atherosclerotic lesions.

  8. Use of platelet-rich plasma solution applied with composite chondrocutaneous graft technique: an experimental study in rabbit model.

    PubMed

    Sevim, Kamuran Zeynep; Yazar, Memet; Irmak, Fatih; Tekkeşin, Merva Soluk; Yildiz, Kemalettin; Sirvan, Selami Serhat

    2014-07-01

    Composite chondrocutaneous grafts have been used widely for patients with cleft lip nasal deformity, alar defects, and septal perforations; however, the graft viability can be easily compromised. The aim of the present study was to extend the safe length of the composite chondrocutaneous grafts by enhancement of angiogenesis and re-epithelialization through platelet-rich plasma (PRP) and to investigate the changes that occur when PRP is administered to the graft and the recipient site. Composite grafts of critical sizes (1.5, 2.0, and 2.5 cm) were planned on the rabbit ears on 1 side. Group A consisted of grafts pretreated with PRP, group B consisted of recipient beds pretreated with PRP, and group C was the control group in which defects 1.5, 2.0, and 2.5 cm in size were formed on the right ears of the rabbits. On postoperative day 7, matching size chondrocutaneous grafts were adapted to the defect areas without PRP. In all groups, graft viability was evaluated 7 days after graft adaptation in group C and 14 days after PRP administration in groups A and B. Wound healing was scored histopathologically and immunohistologically using hematoxylin and eosin, CD34, and smooth muscle actin staining. The terminal transferase fluorescein-dUTP nick end labeling assay was performed to quantitatively demonstrate the apoptosis ratio among the groups. In groups A, B, and C, the mean graft survival of the 2.0-cm equilateral triangle-shaped composite grafts was 65.43% ± 15.7%, 78.12% ± 12.8%, and 41.31% ± 37.4%, respectively (P = .0364). PRP pretreatment accelerated composite graft survival in the 2.0-cm equilateral triangle grafts by increasing epithelial regeneration and fibrosis, inducing neovascularization, and ameliorating apoptosis rates. Copyright © 2014 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  9. Tissue Restoration After Implantation of Polyglycolide, Polydioxanone, Polylevolactide, and Metallic Pins in Cortical Bone: An Experimental Study in Rabbits

    PubMed Central

    Salminen, Sari T.; Tynninen, Olli; Böstman, Ole M.; Laitinen, Outi

    2010-01-01

    We performed qualitative and histoquantitative investigations of tissue restoration after implanting polyglycolide (PGA), polydioxanone (PDS), polylevolactide (PLLA), and stainless steel pins in the intramedullary canal of rabbit femurs. The effect of bioabsorbable devices on healing of a cortical bone defect was also assessed. The cortical bone defect was created in the right femur of 80 rabbits. Bioabsorbable and metallic pins in 60 and two metallic pins alone were implanted in 20 intramedullary canals; 80 left femurs served as intact controls. Follow-up times were 3, 6, 12, 24, and 52 weeks. At all time points, collagenous connective tissue, including bone trabeculae, surrounded the implant at the tissue–implant interface, replacing hematopoiesis and fat of the intramedullary canal. The groups did not differ in the area and trabecular bone area fraction of the resulting callus. Residual fragments of PGA and PDS were observed at 24 weeks, and complete degradation occurred within 52 weeks. PGA, PDS, PLLA, and metallic implants induced a bony and fibrous walling-off response in the intramedullary cavity. No inflammation was observed. Complete tissue restoration did not occur within the follow-up, even after complete degradation of PGA and PDS, which had shorter degradation times than PLLA. The cortical bone healing effect was not different between bioabsorbable pins and metallic wires. Thus, these polymers had no specific osteostimulatory or osteoinhibitory properties compared to stainless steel. Within the follow-up period, there were no significant differences in biocompatibility between the implants and no adverse inflammatory foreign-body reactions. PMID:20495791

  10. [Allograft of cultured chondrocytes into articular cartilage defects in rabbits--experimental study of the repair of articular cartilage injuries].

    PubMed

    Tsuge, H; Sasaki, T; Susuda, K; Abe, K

    1983-08-01

    Articular cartilage defects were created by dill holes, 2 mm wide and 3 mm deep, through the articular cartilage into the subchondral bone in the patellar groove of the femur in mature rabbits. The defects received graft of cultured chondrocytes and the matrix obtained from the primary culture of chondrocytes isolated from the articular cartilage or auricular cartilage in immature rabbits. The isolated cells were cultured for 10 to 14 days. For graft, the cultured chondrocytes together with the matrix were detached from the culture chamber using rubber policemen and centrifuged. The repair of the grafted defects or defects without graft (control) was histologically studied 2 to 12 weeks after operation. The defects without the graft were progressively filled with fibrous tissue containing spindle shaped cells, fibers perpendicular to the surface, and matrix showing weak metachromasia with toluidin blue at 8 weeks. The defects received articular cartilage cell graft were occupied by new cartilage tissue consisting colonylike crumps of chondrocytes 2 weeks after operation. The crumps showed strong metachromasia with toluidin blue and strong stainability for safranin-O. By 4-8 weeks, the defects were filled with homogeneous cartilage. At 12 weeks, arrangement of the chondrocytes of the superficial layer of the new cartilage became columnar as seen in the normal articular cartilage. The defects received elastic cartilage cell graft were filled by reformed cartilage with chondrocytes surrounded by elastic fibers 2-12 weeks after operation. The results indicate that allograft of cultured chondrocytes with matrix into the articular cartilage defects accerated the repair process of the defects by formation of the new cartilage derived from the grafted chondrocytes.

  11. Early bone healing around 2 different experimental, HA grit-blasted, and dual acid-etched titanium implant surfaces. A pilot study in rabbits.

    PubMed

    Gobbato, Luca; Arguello, Emilio; Martin, Ignacio Sanz; Hawley, Charles E; Griffin, Terrence J

    2012-12-01

    To compare early bone healing around different experimental titanium implant surfaces and to evaluate the role of a calcium phosphate-coated implant surface because it relates to bone-implant contact (BIC). An experimental hydroxyapatite (HA) grit-blasted and dual acid-etched titanium surface (BAE-1) was compared to an experimental HA grit-blasted and dual acid-etched surface treated with nanometer-scale crystals of HA (BAE-2). Both experimental implant surfaces were implanted onto the tibias of 4 New Zealand white rabbits. The animals were killed at 1,6, 21, and 90 days after the implant surgery. Descriptive histology was performed at the healing responses of both implant surfaces. Quantitative morphology assessment provided measurements of BIC, number of bone multicellular units (BMUs), average penetration of BMUs, and maximum penetration of BMUs that were manually made using imaging computer software. The overall BIC for the BAE-2 implant was higher than that for the BAE-1 implant at 21 days of healing. However, there was no significant difference at 90 days of healing. It is concluded from this animal pilot study that the bioactive BAE-2 implant surface provided a better BIC with healthy bone remodeling at 21 days of healing.

  12. Theoretical analysis of the neuraminidase epitope of the Mexican A H1N1 influenza strain, and experimental studies on its interaction with rabbit and human hosts.

    PubMed

    Loyola, Paola Kinara Reyes; Campos-Rodríguez, R; Bello, Martiniano; Rojas-Hernández, S; Zimic, Mirko; Quiliano, Miguel; Briz, Verónica; Muñoz-Fernández, M Angeles; Tolentino-López, Luis; Correa-Basurto, Jose

    2013-05-01

    The neuraminidase (NA) epitope from the Mexican AH1N1 influenza virus was identified by using sequences registered at the GenBank during the peak of a pandemic (from April 2009 to October 2010). First, NA protein sequences were submitted for multiple alignment analysis, and their three-dimensional models (3-D) were then built by using homology modeling. The most common sequence (denominated wild-type) and its mutants were submitted to linear and nonlinear epitope predictors, which included the major histocompatibility complex type II (MHC II) and B-cell peptides. The epitope prediction was in accordance with evolutionary behavior and some protein structural properties. The latter included a low NA mutation rate, NA 3-D surface exposure, and the presence of high hindrance side chain residues. After selecting the epitope, docking studies and molecular dynamics (MD) simulations were used to explore interactions between the epitope and MHC II. Afterward, several experimental assays were performed to validate the theoretical study by using antibodies from humans (infected by pandemic H1N1) and rabbits (epitope vaccination). The results show 119 complete sequences that were grouped into 28 protein sequences according to their identity (one wild-type and 27 representative mutants (1-5 mutations)). The predictors yielded several epitopes, with the best fit being the one located in the C-terminal region. Theoretical methods demonstrated that the selected epitope reached the P4, P6, P7, and P9 pockets of MHC II, whereas the experimental evidence indicates that the epitope is recognized by human antibodies and also by rabbit antibodies immunized with the peptide.

  13. Hyperlipoproteinaemia and atherosclerosis in rabbits fed low-level cholesterol and lecithin.

    PubMed Central

    Hunt, C. E.; Duncan, L. A.

    1985-01-01

    Dutch-Belted rabbits were fed for 18 months an atherogenic semipurified gel diet containing 14% hydrogenated coconut oil and 0.06% cholesterol (approximately 0.15 mg/kcal) or a non-atherogenic basal gel diet containing the same ingredients but with no coconut oil or cholesterol. Rabbits fed atherogenic diet developed hypercholesterolaemia (means 733 mg/dl at 16 months) and plasma lipoprotein (LP) distribution shifted from a pattern in which high-density lipoproteins (HDL) predominated to one in which very-low-density lipoproteins (VLDL) were predominant. Total cholesterol/triglyceride ratio in d less than 1.006 LP changed from 0.3 to 1.8. Plasma cholesterol and LP distribution returned to normal in rabbits fed atherogenic diet for 18 months followed by atherogenic diet plus 3% soya lecithin for an additional 4 months. Rabbits fed atherogenic diet for 18 months had extensive, usually full circumference fibromuscular plaques in main branches of coronary arteries and all portions of aorta which compromised lumen area by almost 50%. These lesions were modified in rabbits fed atherogenic diet plus lecithin. The plaques lacked foam cells and cholesterol clefts, were less cellular with a distinct fibrous surface and occupied less space. Animals fed basal diet did not develop hypercholesterolaemia (means 86 mg/dl at 16 months), although distribution of plasma LP shifted slightly in favour of increased low-density lipoproteins (LDL) and decreased HDL compared with rabbits fed standard commercial diet. Basal diet rabbits had no coronary atherosclerosis and only minimal focal foam cell lesions in proximal aorta. Liver injury including fatty change, cholangitis and portal fibrosis occurred in animals fed atherogenic diet. Thus, rabbits fed appropriate diets low in cholesterol accumulate cholesterol-enriched LP in their plasma and develop lesions in abdominal aorta and main branches of coronary arteries which are similar to those in man. Also, in this experimental model

  14. Fluorescence imaging of macrophages in atherosclerotic plaques using plasmonic gold nanorose

    NASA Astrophysics Data System (ADS)

    Wang, Tianyi; Sapozhnikova, Veronika; Mancuso, J. Jacob; Willsey, Brian; Qiu, Jinze; Ma, Li L.; Li, Xiankai; Johnston, Keith P.; Feldman, Marc D.; Milner, Thomas E.

    2011-03-01

    Macrophages are one of the most important cell types involved in the progression of atherosclerosis which can lead to myocardial infarction. To detect macrophages in atherosclerotic plaques, plasmonic gold nanorose is introduced as a nontoxic contrast agent for fluorescence imaging. We report macrophage cell culture and ex vivo tissue studies to visualize macrophages targeted by nanorose using scanning confocal microscopy. Atherosclerotic lesions were created in the aorta of a New Zealand white rabbit model subjected to a high cholesterol diet and double balloon injury. The rabbit was injected with nanoroses coated with dextran. A HeNe laser at 633 nm was used as an excitation light source and a acousto-optical beam splitter was utilized to collect fluorescence emission in 650-760 nm spectral range. Results of scanning confocal microscopy of macrophage cell culture and ex vivo tissue showed that nanoroses produce a strong fluorescence signal. The presence of nanorose in ex vivo tissue was further confirmed by photothermal wave imaging. These results suggest that scanning confocal microscopy can identify the presence and location of nanorose-loaded macrophages in atherosclerotic plaques.

  15. The effect of experimental ischaemia and excitatory amino acid agonists on the GABA and serotonin immunoreactivities in the rabbit retina.

    PubMed

    Osborne, N N; Herrera, A J

    1994-04-01

    The aim of the described experiments was to use immunohistochemistry to visualize the release of GABA from specific retinal amacrine cells following ischaemia and to establish the involvement of defined glutamatergic receptors. In initial experiments, rabbit retinas were exposed in vitro to excitatory amino acid agonists alone or in combination with a putative antagonist, or in physiological solution lacking oxygen and glucose, or in solution containing potassium cyanide for 45 min at 37 degrees C. The nature of the GABA immunoreactivity was then examined by immunohistochemistry. In other in vitro experiments, retinas were first allowed to accumulate exogenous serotonin before exposing the tissues to the combinations as described. These tissues were then processed immunohistochemically for the localization of serotonin. In yet other experiments, the intraocular pressure of a rabbit's eye was raised to about 110 mmHg for 60 min and a reperfusion time of 45 min allowed before dissecting the retina and processing for the localization of GABA immunoreactivity. The other eye served as a control. Of the excitatory amino acid agonists tested, only N-methyl-D-aspartate, kainate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid caused a change in the GABA immunoreactivity. The N-methyl-D-aspartate effect was specifically antagonized by dizocilpine maleate, dextromethorphan and memantine, and was characterized by a reduction in the number of GABA-immunoreactive perikarya. The GABA "staining" in the inner plexiform layer also appeared as four clear bands. The alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid- and kainate-induced effects were both antagonized by 6-cyano-2,3-dihydroxy-7-nitroquinoxaline-2,3-dione and partially by kynurenic acid at the concentrations used. Here, the amount of GABA-positive perikarya was greatly reduced and three immunoreactive bands appeared in the inner plexiform layer. However, for low concentrations of alpha-amino-3-hydroxy

  16. The NF-κB pathway: regulation of the instability of atherosclerotic plaques activated by Fg, Fb, and FDPs.

    PubMed

    Cao, Yongjun; Zhou, Xiaomei; Liu, Huihui; Zhang, Yanlin; Yu, Xiaoyan; Liu, Chunfeng

    2013-11-01

    Recently, the molecular mechanism responsible for the instability of atherosclerotic plaques has gradually become a hot topic among researchers and clinicians. Matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) play an important role in the processes of formation and development of atherosclerosis. In this study, we established and employed the transwell co-culture system of rabbit aortic endothelial cells and smooth muscle cells to explore the relationship between fibrin (Fb), fibrinogen (Fg), and/or their degradation products (FDPs) in relation to the instability of atherosclerotic plaques; meanwhile, we observed the effects of Fg, Fb, and FDPs on the mRNA levels of MMPs and VEGF as well as on the activation of nuclear factor-kappa B (NF-κB). We concluded that Fb, Fg, and FDPs are involved in the progression of the instability of atherosclerotic plaques via increasing the expression of MMPs and VEGF. This effect might be mediated by the NF-кB pathway.

  17. The use of methylene blue in the treatment of anaphylactic shock induced by compound 48/80: experimental studies in rabbits.

    PubMed

    Buzato, Marcelo A S; Viaro, Fernanda; Piccinato, Carlos E; Evora, Paulo R B

    2005-06-01

    In this study, the isolated use of methylene blue (MB) in the treatment of anaphylactic shock induced by Compound 48/80 (C48/80), a potent histamine releaser, was examined, and the study of the effects of MB on the function of the aorta artery endothelium was accomplished in vitro. MB was used in a single 3.0 mg/kg dose, and C48/80 was used in a single 4.5 mg/kg dose. The study protocol included the following experimental groups, containing six animals each: group I (control), animals in the absence of any drug action; group II (MB), MB infusion; Group III (C48/80), anaphylactic shock induced by using C48/80; group IV (C48/80 + MB), anaphylactic shock treated with MB infusion at the moment of major hypotension; and group V (MB + C48/80), prevention of anaphylactic shock with MB by means of MB infusion minutes before the 4.5 mg/kg C48/80 infusion. Nitric oxide plasma levels were measured in each of the experimental groups. After the in vivo studies were performed, an in vitro study was conducted using segments of the abdominal aortas of the rabbits to determine the effect of MB on the arterial endothelium. The results obtained in the present investigation have shown that MB intravenous infusion does not change the mean arterial pressure when compared with the control group (n = 6 in each group, P < 0.05); that C48/80 is effective in producing experimental anaphylactic shock (n = 6, P < 0.05); that the attempt to prevent anaphylactic shock with MB results in a mean prolongation of animal survival ranging from 17 to 34 min (n = 6 in each group, P < 0.05); that MB is effective in reversing anaphylactic shock in all the studied rabbits (n = 6, P < 0.05); that absolute and percentage plasma nitrate values obtained with the experimental groups do not differ (n = 6, each group, P < 0.05); and that the in vitro study of segments of abdominal aorta has shown that there has not been endothelial dysfunction in any of the groups (n = 6 in each group, P < 0.05). The good results

  18. An experimental study of postoperative monitoring for innervated free muscle graft by the compound muscle action potential in rabbits.

    PubMed

    Tan, Soo-Heong; Shigetomi, Mitsunori; Doi, Kazuteru

    2012-07-01

    This experiment establishes the principles of using the compound muscle action potential (CMAP) as a possible postoperative monitor for free muscle grafts. Twenty rabbits were divided into two groups of ten each to investigate the effects of ischemia on CMAP of the muscles. Rectus femoris model was used and contralateral muscle was used as control. In all muscles total normothermic ischemia of 1.5 hours to mimic the time needed for transfer and inset of the flap was followed by occlusion of the artery in one group and vein in another group after 3 hours. During this ischemia of 1 hour, the CMAP amplitudes decreased and the latencies were prolonged. Latency prolongation was detected within 10 minutes of total, arterial, or venous ischemia. During the revascularization, both amplitude and latency improved, but not to the original values at the start. The results show that CMAP monitoring can provide easily detectable, objective indication of vascular compromise to a muscle graft within as early as 10 minutes of total, arterial, and venous ischemia. Changes in latency are more constant and predictable compared with amplitude changes. This method can provide continuous monitoring and can be used in buried muscle grafts.

  19. Sinus mucosa elevation using Bio-Oss(®) or Gingistat(®) collagen sponge: an experimental study in rabbits.

    PubMed

    Caneva, Marco; Lang, Niklaus P; Garcia Rangel, Idelmo Junior; Ferreira, Sabrina; Caneva, Martina; De Santis, Enzo; Botticelli, Daniele

    2017-07-01

    To describe the sequential healing in augmented sinus cavities with deproteinized bovine bone mineral (DBBM) granules or collagen sponges. Twenty albino New Zealand rabbits were included in the study. An incision was performed along the midline of the nasal dorsum, and the nasal bone was exposed. Circular bony windows with a diameter of 5 mm were prepared bilaterally. After elevation of the mucosa, the two sites were randomly filled with either DBBM or a collagen sponge. Five animals each were randomly sacrificed after 7, 14, 21 and 40 days, respectively. At both sides, new bone was found forming from the resident pristine bone. During the first stage of healing, DBBM granules were surrounded by a denser connective tissue that was attached to the biomaterial surface and that was progressively mineralized. At the collagen sponge side, the biomaterial was almost completely resorbed and the space was reduced by to two-thirds already after 21 days. At both sides, after 40 days, mineralized bone and marrow spaces were occupying large areas of the elevated space. New bone was found forming from the pristine bony walls of the sinus and extending toward the most peripheral regions in both sites. While DBBM particles yielded osteoconductivity and were able to preserve over time the space within the elevated mucosa, the collagen sponge failed the goal of maintaining the space. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. THE MECHANISM OF ACTION OF 17-HYDROXY-11-DEHYDROCORTICOSTERONE (COMPOUND E) AND OF THE ADRENOCORTICOTROPIC HORMONE IN EXPERIMENTAL HYPERSENSITIVITY IN RABBITS

    PubMed Central

    Germuth, Frederick G.; Oyama, Jiro; Ottinger, Barbara

    1951-01-01

    The concurrent administration of compound E at a daily dosage of 2 mg. per kg. to rabbits receiving daily intracutaneous injections of crystalline egg albumin markedly inhibited the development of anaphylactic hypersensitivity of the Arthus type. ACTH, when given at a similar dosage, produced a much less marked effect. Both hormones suppressed circulating antibody and as with the Arthus reaction, the suppression produced by compound E was much greater than that obtained with ACTH. When treatment with compound E was started following sensitization, there was a rapid decline in circulating antibody and, if the pretreatment serum antibody was low, there was also a progressive decrease in skin reactivity, becoming negative after 5 days of treatment. When the pretreatment serum antibody concentration was great, so that by the termination of treatment the antibody concentration was still above the level ordinarily sufficient for a maximal skin response, the Arthus reaction was unaffected by treatment. These considerations as well as the failure of compound E to inhibit the systemic passive Arthus reaction suggest that the inhibitory effect of compound E and ACTH on the development of experimental hypersensitivity results from the hormonal reduction of circulating antibody. Treatment with compound E had no effect on the rate of disappearance of circulating antibody in the passively immunized rabbit. This finding suggests that ACTH and compound E reduce circulating antibody by inhibiting antibody formation rather than by promoting antibody destruction. The question is raised as to whether the marked lymphoid atrophy produced by these hormones may be related to the interference with antibody production. PMID:14861375

  1. Cilostazol Inhibits Accumulation of Triglyceride in Aorta and Platelet Aggregation in Cholesterol-Fed Rabbits

    PubMed Central

    Ito, Hideki; Uehara, Kenji; Matsumoto, Yutaka; Hashimoto, Ayako; Nagano, Chifumi; Niimi, Manabu; Miyakoda, Goro; Nagano, Keisuke

    2012-01-01

    Cilostazol is clinically used for the treatment of ischemic symptoms in patients with chronic peripheral arterial obstruction and for the secondary prevention of brain infarction. Recently, it has been reported that cilostazol has preventive effects on atherogenesis and decreased serum triglyceride in rodent models. There are, however, few reports on the evaluation of cilostazol using atherosclerotic rabbits, which have similar lipid metabolism to humans, and are used for investigating the lipid content in aorta and platelet aggregation under conditions of hyperlipidemia. Therefore, we evaluated the effect of cilostazol on the atherosclerosis and platelet aggregation in rabbits fed a normal diet or a cholesterol-containing diet supplemented with or without cilostazol. We evaluated the effects of cilostazol on the atherogenesis by measuring serum and aortic lipid content, and the lesion area after a 10-week treatment and the effect on platelet aggregation after 1- and 10-week treatment. From the lipid analyses, cilostazol significantly reduced the total cholesterol, triglyceride and phospholipids in serum, and moreover, the triglyceride content in the atherosclerotic aorta. Cilostazol significantly reduced the intimal atherosclerotic area. Platelet aggregation was enhanced in cholesterol-fed rabbits. Cilostazol significantly inhibited the platelet aggregation in rabbits fed both a normal diet and a high cholesterol diet. Cilostazol showed anti-atherosclerotic and anti-platelet effects in cholesterol-fed rabbits possibly due to the improvement of lipid metabolism and the attenuation of platelet activation. The results suggest that cilostazol is useful for prevention and treatment of atherothrombotic diseases with the lipid abnormalities. PMID:22761774

  2. Approach to atherosclerotic renovascular disease: 2016

    PubMed Central

    Daloul, Reem; Morrison, Aubrey R.

    2016-01-01

    The management of atherosclerotic renal artery stenosis in patients with hypertension or impaired renal function remains a clinical dilemma. The current general consensus, supported by the results of the Angioplasty and Stenting for Renal Atherosclerotic Lesions and Cardiovascular Outcomes for Renal Artery Lesions trials, argues strongly against endovascular intervention in favor of optimal medical management. We discuss the limitations and implications of the contemporary clinical trials and present our approach and formulate clear recommendations to help with the management of patients with atherosclerotic narrowing of the renal artery. PMID:27679718

  3. Oculoscopy in Rabbits and Rodents.

    PubMed

    Jekl, Vladimir; Hauptman, Karel; Knotek, Zdenek

    2015-09-01

    Ophthalmic diseases are common in rabbits and rodents. Fast and definitive diagnosis is imperative for successful treatment of ocular diseases. Ophthalmic examination in rabbits and rodents can be challenging. Oculoscopy offers great magnification for the examination of the ocular structures in such animals, including the evaluation of cornea, anterior eye chamber, limbus, iris, lens, and retina. To date, oculoscopy has been described only sporadically and/or under experimental conditions. This article describes the oculoscopy technique, normal and abnormal ocular findings, and the most common eye disorders diagnosed with the aid of endoscopy in rabbits and rodents.

  4. The immunology of experimental Chagas' disease. IV. Production of lesions in rabbits similar to those of chronic Chagas' disease in man.

    PubMed Central

    Teixeira, A. R.; Teixeira, M. L.; Santos-Buch, C. A.

    1975-01-01

    Eight rabbits that received a single inoculation of trypomastigotes of a virulent strain of Trypanosoma cruzi first developed a transient acute illness associated with parasitemia; later, 4 of these rabbits died with chronic myocarditis and/or with megacolon in the absence of demonstrable parasitemia or encysted parasites in tissues. Two of these rabbits with chronic myocarditis died unexpectedly. Three of the inoculated rabbits that survived the infection were sacrificed 18 months later and showed similar but less severe microscopic lesions. The remaining rabbit is alive and well at the time of writing (26 months) with negative blood cultures but high hemagglutinating antibody titers to T. cruzi antigens. The natural course of T. cruzi infection in rabbits and the lesions observed postmortem are similar to those recorded for humans with chronic Chagas' disease. Multiple injections of particulate subcellular antigens of T. cruzi in rabbits resulted in microscopic lesions similar to those observed in rabbits that survived protozoan infection. Sera of rabbits inoculated with T. cruzi have antibodies to striated and smooth muscle structures. However, evidence provided in this and in other experiments strongly suggest that the lesions of chronic Chagas' disease are produced by delayed hypersensitivity to T. cruzi antigens. Images Figure 1 Figure 2 Figures 3-4 Figure 5 Figure 6 Figure 7 PMID:808136

  5. Mucosal Administration of Collagen V Ameliorates the Atherosclerotic Plaque Burden by Inducing Interleukin 35-dependent Tolerance.

    PubMed

    Park, Arick C; Huang, Guorui; Jankowska-Gan, Ewa; Massoudi, Dawiyat; Kernien, John F; Vignali, Dario A; Sullivan, Jeremy A; Wilkes, David S; Burlingham, William J; Greenspan, Daniel S

    2016-02-12

    We have shown previously that collagen V (col(V)) autoimmunity is a consistent feature of atherosclerosis in human coronary artery disease and in the Apoe(-/-) mouse model. We have also shown sensitization of Apoe(-/-) mice with col(V) to markedly increase the atherosclerotic burden, providing evidence of a causative role for col(V) autoimmunity in atherosclerotic pathogenesis. Here we sought to determine whether induction of immune tolerance to col(V) might ameliorate atherosclerosis, providing further evidence for a causal role for col(V) autoimmunity in atherogenesis and providing insights into the potential for immunomodulatory therapeutic interventions. Mucosal inoculation successfully induced immune tolerance to col(V) with an accompanying reduction in plaque burden in Ldlr(-/-) mice on a high-cholesterol diet. The results therefore demonstrate that inoculation with col(V) can successfully ameliorate the atherosclerotic burden, suggesting novel approaches for therapeutic interventions. Surprisingly, tolerance and reduced atherosclerotic burden were both dependent on the recently described IL-35 and not on IL-10, the immunosuppressive cytokine usually studied in the context of induced tolerance and amelioration of atherosclerotic symptoms. In addition to the above, using recombinant protein fragments, we were able to localize two epitopes of the α1(V) chain involved in col(V) autoimmunity in atherosclerotic Ldlr(-/-) mice, suggesting future courses of experimentation for the characterization of such epitopes.

  6. Imaging the Efficacy of Anti-Inflammatory Liposomes in a Rabbit Model of Atherosclerosis by Non-Invasive Imaging

    PubMed Central

    Lobatto, Mark E.; Calcagno, Claudia; Metselaar, Josbert M.; Storm, Gert; Stroes, Erik S. G.; Fayad, Zahi A.; Mulder, Willem J. M.

    2013-01-01

    Nanomedicine can provide a potent alternative to current therapeutic strategies for atherosclerosis. For example, the encapsulation of anti-inflammatory drugs into liposomes improves their pharmacokinetics and biodistribution, thereby enhancing bioavailability to atherosclerotic plaques and improving therapeutic efficacy. The evaluation of this type of experimental therapeutics can greatly benefit from in vivo evaluation to assess biological changes, which can be performed by non-invasive imaging techniques, such as 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Here, we will illustrate the methods for inducing atherosclerosis in a rabbit model, the production of anti-inflammatory liposomes and monitoring of therapeutic efficacy of experimental therapeutics with the above-mentioned imaging techniques. PMID:22449928

  7. Imaging the efficacy of anti-inflammatory liposomes in a rabbit model of atherosclerosis by non-invasive imaging.

    PubMed

    Lobatto, Mark E; Calcagno, Claudia; Metselaar, Josbert M; Storm, Gert; Stroes, Erik S G; Fayad, Zahi A; Mulder, Willem J M

    2012-01-01

    Nanomedicine can provide a potent alternative to current therapeutic strategies for atherosclerosis. For example, the encapsulation of anti-inflammatory drugs into liposomes improves their pharmacokinetics and biodistribution, thereby enhancing bioavailability to atherosclerotic plaques and improving therapeutic efficacy. The evaluation of this type of experimental therapeutics can greatly benefit from in vivo evaluation to assess biological changes, which can be performed by non-invasive imaging techniques, such as ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Here, we will illustrate the methods for inducing atherosclerosis in a rabbit model, the production of anti-inflammatory liposomes and monitoring of therapeutic efficacy of experimental therapeutics with the above-mentioned imaging techniques.

  8. Transmission of Hepatitis E Virus from Rabbits to Cynomolgus Macaques

    PubMed Central

    Liu, Peng; Bu, Qiu-Ning; Han, Jian; Du, Ren-Jie; Lei, Ya-Xin; Ouyang, Yu-Qing; Li, Jie; Zhu, Yong-Hong; Lu, Feng-Min; Zhuang, Hui

    2013-01-01

    The recent discovery of hepatitis E virus (HEV) strains in rabbits in the People’s Republic of China and the United States revealed that rabbits are another noteworthy reservoir of HEV. However, whether HEV from rabbits can infect humans is unclear. To study the zoonotic potential for and pathogenesis of rabbit HEV, we infected 2 cynomolgus macaques and 2 rabbits with an HEV strain from rabbits in China. Typical hepatitis developed in both monkeys; they exhibited elevated liver enzymes, viremia, virus shedding in fecal specimens, and seroconversion. Comparison of the complete genome sequence of HEV passed in the macaques with that of the inoculum showed 99.8% nucleotide identity. Rabbit HEV RNA (positive- and negative-stranded) was detectable in various tissues from the experimentally infected rabbits, indicating that extrahepatic replication may be common. Thus, HEV is transmissible from rabbits to cynomolgus macaques, which suggests that rabbits may be a new source of human HEV infection. PMID:23628346

  9. [18F]FDG Uptake in the Aortic Wall Smooth Muscle of Atherosclerotic Plaques in the Simian Atherosclerosis Model

    PubMed Central

    Mizuma, Hiroshi; Hokamura, Kazuya; Onoe, Hirotaka; Umemura, Kazuo

    2016-01-01

    Atherosclerosis is a self-sustaining inflammatory fibroproliferative disease that progresses in discrete stages and involves a number of cell types and effector molecules. Recently, [18F]fluoro-2-deoxy-D-glucose- ([18F]FDG-) positron emission tomography (PET) has been suggested as a tool to evaluate atherosclerotic plaques by detecting accumulated macrophages associated with inflammation progress. However, at the cellular level, it remains unknown whether only macrophages exhibit high uptake of [18F]FDG. To identify the cellular origin of [18F]FDG uptake in atherosclerotic plaques, we developed a simian atherosclerosis model and performed PET and ex vivo macro- and micro-autoradiography (ARG). Increased [18F]FDG uptake in the aortic wall was observed in high-cholesterol diet-treated monkeys and WHHL rabbits. Macro-ARG of [18F]FDG in aortic sections showed that [18F]FDG was accumulated in the media and intima in the simian model as similar to that in WHHL rabbits. Combined analysis of micro-ARG with immunohistochemistry in the simian atherosclerosis model revealed that most cellular [18F]FDG uptake observed in the media was derived not only from the infiltrated macrophages in atherosclerotic plaques but also from the smooth muscle cells (SMCs) of the aortic wall in atherosclerotic lesions. PMID:28101514

  10. [(18)F]FDG Uptake in the Aortic Wall Smooth Muscle of Atherosclerotic Plaques in the Simian Atherosclerosis Model.

    PubMed

    Iwaki, Takayuki; Mizuma, Hiroshi; Hokamura, Kazuya; Onoe, Hirotaka; Umemura, Kazuo

    2016-01-01

    Atherosclerosis is a self-sustaining inflammatory fibroproliferative disease that progresses in discrete stages and involves a number of cell types and effector molecules. Recently, [(18)F]fluoro-2-deoxy-D-glucose- ([(18)F]FDG-) positron emission tomography (PET) has been suggested as a tool to evaluate atherosclerotic plaques by detecting accumulated macrophages associated with inflammation progress. However, at the cellular level, it remains unknown whether only macrophages exhibit high uptake of [(18)F]FDG. To identify the cellular origin of [(18)F]FDG uptake in atherosclerotic plaques, we developed a simian atherosclerosis model and performed PET and ex vivo macro- and micro-autoradiography (ARG). Increased [(18)F]FDG uptake in the aortic wall was observed in high-cholesterol diet-treated monkeys and WHHL rabbits. Macro-ARG of [(18)F]FDG in aortic sections showed that [(18)F]FDG was accumulated in the media and intima in the simian model as similar to that in WHHL rabbits. Combined analysis of micro-ARG with immunohistochemistry in the simian atherosclerosis model revealed that most cellular [(18)F]FDG uptake observed in the media was derived not only from the infiltrated macrophages in atherosclerotic plaques but also from the smooth muscle cells (SMCs) of the aortic wall in atherosclerotic lesions.

  11. Effectiveness of Two Methods for Preparation of Autologous Platelet-Rich Plasma: An Experimental Study in Rabbits

    PubMed Central

    Nagata, Maria J. H.; Messora, Michel R.; Furlaneto, Flávia A. C.; Fucini, Stephen E.; Bosco, Alvaro F.; Garcia, Valdir G.; Deliberador, Tatiana M.; de Melo, Luiz G. N.

    2010-01-01

    Objectives: The purpose of this study was to compare the quantity and quality of platelets in platelet-rich plasma (PRP) samples prepared using either the single- or the double-centrifugation protocol. Methods: Ten adult white New Zealand rabbits were used. Ten ml of blood were drawn from each animal via cardiac puncture. Each blood sample was divided into two equal parts for PRP preparation: 5 ml of blood were centrifuged according to a single-centrifugation protocol (Group I), and 5 ml were centrifuged according to a double-centrifugation protocol (Group II). Manual platelet counts were performed on the whole blood and PRP samples of each group. Smears were also done on all samples in order to see the morphology of the platelets. The data obtained in the manual platelet count were submitted to statistical analysis (repeated measures ANOVA, Tukey, P<.05). Results: The average whole blood platelet count was 446,389/μl. The PRP samples in Group II presented an average platelet amount significantly higher than that of Group I (1,986,875 ± 685,020/μl and 781,875 ± 217,693/μl, respectively). The PRP smears from Group II were the only one to present platelets with altered morphology (75% of the smears). A few lymphocytes with increased cytoplasm were observed in the PRP smears of both Groups I (25% of the smears) and II (62.5% of the smears). Conclusions: Within the limits of this study, it can be concluded that the double-centrifugation protocol resulted in higher platelet concentrations than did the single-centrifugation protocol. However, the double-centrifugation protocol caused alterations in platelet morphology and was more sensitive to small processing errors. PMID:20922159

  12. Combinatorial administration of insulin and vitamin C alleviates the cerebral vasospasm after experimental subarachnoid hemorrhage in rabbit

    PubMed Central

    2011-01-01

    Background Cerebral vasospasm (CVS) is a common serious complication after the spontaneous subarachnoid hemorrhage (SAH). Despite recent advances in medical and surgical treatments, the 30-day mortality rate of SAH remains high, and there is lack of especially effective clinical treatment to alleviate and improve CVS. The present study has investigated the therapeutic effect of insulin and vitamin C on CVS after SAH. Results Five days after SAH, there is obvious basilar artery spasm in SAH group, whose average vascular cross-sectional area (233,099 ± 16,750 μm2) is significantly smaller than that in control group (462,128 ± 74,756 μm2), which is also significantly different from those in SAH + insulin group (221,114 ± 43,457 μm2) and SAH + vitamin C group (237,820 ± 21,703 μm2). SAH + insulin + vitamin C group shows no evident vasospasm and maintains a vascular cross-sectional area of 425,530 ± 45,503 μm2, which is significantly different from that in SAH group. Insulin receptor α (InRα) expression is significantly downregulated in the vascular endothelial cells of SAH, SAH + insulin, and SAH + vitamin C groups (P < 0.01) but remains unchanged in vascular endothelial cells of SAH + insulin + vitamin C group (P > 0.05). Five days after SAH, serum and cerebrospinal fluid NO levels in SAH, SAH + insulin, and SAH + vitamin C groups decrease significantly (P < 0.01) compared to that in control group, whereas the reduction is not evident in SAH + insulin + vitamin C group (P > 0.05). Conclusion Combinatorial treatment with insulin and vitamin C has effectively relieved the CVS after SAH in rabbit, possibly through increasing the InRα expression and NO level, whereas treatment with insulin or vitamin C alone fails to do so. PMID:21801458

  13. Effect of surfactant on regional lung function in an experimental model of respiratory distress syndrome in rabbit.

    PubMed

    Bayat, Sam; Porra, Liisa; Broche, Ludovic; Albu, Gergely; Malaspinas, Iliona; Doras, Camille; Strengell, Satu; Peták, Ferenc; Habre, Walid

    2015-08-01

    We assessed the changes in regional lung function following instillation of surfactant in a model of respiratory distress syndrome (RDS) induced by whole lung lavage and mechanical ventilation in eight anaesthetized, paralyzed, and mechanically ventilated New Zealand White rabbits. Regional specific ventilation (sV̇) was measured by K-edge subtraction synchrotron computed tomography during xenon washin. Lung regions were classified as poorly aerated (PA), normally aerated (NA), or hyperinflated (HI) based on regional density. A functional category was defined within each class based on sV̇ distribution (High, Normal, and Low). Airway resistance (Raw), respiratory tissue damping (G), and elastance (H) were measured by forced oscillation technique at low frequencies before and after whole lung saline lavage-induced (100 ml/kg) RDS, and 5 and 45 min after intratracheal instillation of beractant (75 mg/kg). Surfactant instillation improved Raw, G, and H (P < 0.05 each), and gas exchange and decreased atelectasis (P < 0.001). It also significantly improved lung aeration and ventilation in atelectatic lung regions. However, in regions that had remained normally aerated after lavage, it decreased regional aeration and increased sV̇ (P < 0.001) and sV̇ heterogeneity. Although surfactant treatment improved both central airway and tissue mechanics and improved regional lung function of initially poorly aerated and atelectatic lung, it deteriorated regional lung function when local aeration was normal prior to administration. Local mechanical and functional heterogeneity can potentially contribute to the worsening of RDS and gas exchange. These data underscore the need for reassessing the benefits of routine prophylactic vs. continuous positive airway pressure and early "rescue" surfactant therapy in very immature infants.

  14. Pharmacokinetics of the toxic fraction of Centruroides limpidus limpidus venom in experimentally envenomed rabbits and effects of immunotherapy with specific F(ab')2.

    PubMed

    Calderón-Aranda, E S; Rivière, G; Choumet, V; Possani, L D; Bon, C

    1999-05-01

    Envenomations after scorpion stings are a major health problem throughout the world. Their specific treatment is immunotherapy which consists of the injection of specific antibody. In this article, we studied the pharmacokinetics of the toxic fraction of Centruroides limpidus limpidus venom (fraction II) in experimentally envenomed rabbits. After an intravenous injection, fraction II (FII) was rapidly distributed and eliminated from the body (terminal half-life of 1.9 h). When injected subcutaneously, high concentrations of FII were measured in the vascular space rapidly after the injection (Tmax = 1 h) and FII was eliminated with a terminal half-life of 1.8 h, close to that determined after intravenous injection. These observations go along with the rapid onset of clinical symptoms observed after accidental envenomations. To investigate the mechanism of action of antivenom, we examined the effects of the intravenous administration of antivenom (horse F(ab')2 directed against Centruroides venoms) on the pharmacokinetics of FII. Immunotherapy performed 2 h after the experimental envenomation largely increased the area under the concentration time curve of FII compared to that calculated in absence of immunotherapy (13,000 versus 170 ng h ml(-1), respectively). These observations agree with previous findings which showed that specific antibody fragments are able to remove drugs from their site of action and sequester them in the vascular space. These studies provide a powerful tool to determine an excellent procedure for further improvement of immunotherapy.

  15. LOX-1 in atherosclerotic disease.

    PubMed

    Sawamura, Tatsuya; Wakabayashi, Ichiro; Okamura, Tomonori

    2015-02-02

    Oxidized low-density lipoprotein (LDL) exhibits various biological activities and accumulates in atheromas. LOX-1 (lectin-like oxidized LDL receptor) is the receptor that mediates oxidized LDL activity in vascular endothelial cells. Activation of LOX-1 results in oxidized LDL-induced endothelial dysfunction and hyperlipidemia-induced vascular lipid deposition. We hypothesized that LOX-1 is a candidate risk factor beyond LDL cholesterol (LDLC) and developed a novel assay to quantify LOX-1 ligand containing apoB (LAB). In men from the United States, serum LAB showed a significant positive association with carotid intima-media thickness, independent of LDLC. LAB and the LOX index (obtained by multiplying LAB by sLOX-1) were significantly associated with the incidence of coronary artery disease and ischemic stroke after adjusting for confounding factors, including non-HDL cholesterol. sLOX-1 is thought to be a better biomarker for early diagnosis of acute coronary syndrome than traditional biomarkers, including troponin T. LAB was associated with various atherosclerotic risk factors such as smoking, obesity, diabetes, diastolic hypertension, hypertriglyceridemia, and metabolic syndrome. Measurement of the soluble form of LOX-1 (sLOX-1) and LAB seems to be useful for evaluating the state and risk of atherosclerosis and atherosclerosis-related diseases. Further prospective studies using large populations and randomized clinical trials on sLOX-1, LAB, and the LOX index are needed.

  16. Atherosclerotic plaque targeting mechanism of long-circulating nanoparticles established by multimodal imaging.

    PubMed

    Lobatto, Mark E; Calcagno, Claudia; Millon, Antoine; Senders, Max L; Fay, Francois; Robson, Philip M; Ramachandran, Sarayu; Binderup, Tina; Paridaans, Maarten P M; Sensarn, Steven; Rogalla, Stephan; Gordon, Ronald E; Cardoso, Luis; Storm, Gert; Metselaar, Josbert M; Contag, Christopher H; Stroes, Erik S G; Fayad, Zahi A; Mulder, Willem J M

    2015-02-24

    Atherosclerosis is a major cause of global morbidity and mortality that could benefit from novel targeted therapeutics. Recent studies have shown efficient and local drug delivery with nanoparticles, although the nanoparticle targeting mechanism for atherosclerosis has not yet been fully elucidated. Here we used in vivo and ex vivo multimodal imaging to examine permeability of the vessel wall and atherosclerotic plaque accumulation of fluorescently labeled liposomal nanoparticles in a rabbit model. We found a strong correlation between permeability as established by in vivo dynamic contrast enhanced magnetic resonance imaging and nanoparticle plaque accumulation with subsequent nanoparticle distribution throughout the vessel wall. These key observations will enable the development of nanotherapeutic strategies for atherosclerosis.

  17. Selective ablation of atherosclerotic lesions with less thermal damage by controlling the pulse structure of a quantum cascade laser in the 5.7-µm wavelength range

    NASA Astrophysics Data System (ADS)

    Hashimura, Keisuke; Ishii, Katsunori; Awazu, Kunio

    2016-04-01

    Cholesteryl esters are the main components of atherosclerotic plaques, and they have an absorption peak at the wavelength of 5.75 µm. To realize less-invasive ablation of the atherosclerotic plaques using a quasi-continuous wave (quasi-CW) quantum cascade laser (QCL), the thermal effects on normal vessels must be reduced. In this study, we attempted to reduce the thermal effects by controlling the pulse structure. The irradiation effects on rabbit atherosclerotic aortas using macro pulse irradiation (irradiation of pulses at intervals) and conventional quasi-CW irradiation were compared. The macro pulse width and the macro pulse interval were determined based on the thermal relaxation time of atherosclerotic and normal aortas in the oscillation wavelength of the QCL. The ablation depth increased and the coagulation width decreased using macro pulse irradiation. Moreover, difference in ablation depth between the atherosclerotic and normal rabbit aortas using macro pulse irradiation was confirmed. Therefore, the QCL in the 5.7-µm wavelength range with controlling the pulse structure was effective for less-invasive laser angioplasty.

  18. Vorapaxar in atherosclerotic disease management.

    PubMed

    Cheng, Judy W M; Colucci, Vincent; Howard, Patricia A; Nappi, Jean M; Spinler, Sarah A

    2015-05-01

    To review the pharmacology, efficacy, and safety of vorapaxar, a protease activator receptor-1 (PAR-1) antagonist, in the management of atherosclerotic diseases. Peer-reviewed clinical trials and review articles were identified from MEDLINE and Current Content database (both 1966 to December 31, 2014) using the search terms vorapaxar and protease activator receptor antagonist. A total of 30 clinical studies were identified (16 clinical trials, including subanalyses, 14 related to pharmacology, pharmacokinetics, and pharmacodynamics and drug interactions). Two phase III clinical trials with vorapaxar have been published. In patients with non-ST segment elevation myocardial infarction (MI), vorapaxar failed to significantly reduce the primary efficacy end point (composite of cardiovascular death, MI, stroke, recurrent ischemia with hospitalization, and urgent coronary revascularization). Conversely, in a study of secondary prevention for patients with cardiovascular disease, the composite end point of cardiovascular death, MI, or stroke was significantly reduced. In both trials, the safety end points of major/minor bleeding were increased compared with placebo. In the secondary prevention trial, an increased incidence of intracranial hemorrhage led to the exclusion of patients with a prior history of stroke. Vorapaxar is approved for use with aspirin and/or clopidogrel in the secondary prevention of cardiovascular events in stable patients with peripheral arterial disease or a history of MI. However, the addition of vorapaxar to other antiplatelets can significantly increase the risk of bleeding. It is, therefore, essential to balance the need for further reduction of risk of thrombotic event with patient's individual bleeding risk. © The Author(s) 2015.

  19. Increased platelet deposition on atherosclerotic coronary arteries.

    PubMed Central

    van Zanten, G H; de Graaf, S; Slootweg, P J; Heijnen, H F; Connolly, T M; de Groot, P G; Sixma, J J

    1994-01-01

    A ruptured atherosclerotic plaque leads to exposure of deeper layers of the plaque to flowing blood and subsequently to thrombus formation. In contrast to the wealth of data on the occurrence of thrombi, little is known about the reasons why an atherosclerotic plaque is thrombogenic. One of the reasons is the relative inaccessibility of the atherosclerotic plaque. We have circumvented this problem by using 6-microns cryostat cross sections of human coronary arteries. These sections were mounted on coverslips that were exposed to flowing blood in a rectangular perfusion chamber. In normal-appearing arteries, platelet deposition was seen on the luminal side of the intima and on the adventitia. In atherosclerotic arteries, strongly increased platelet deposition was seen on the connective tissue of specific parts of the atherosclerotic plaque. The central lipid core of an advanced plaque was not reactive towards platelets. The results indicate that the atherosclerotic plaque by itself is more thrombogenic than the normal vessel wall. To study the cause of the increased thrombus formation on the atherosclerotic plaque, perfusion studies were combined with immunohistochemical studies. Immunohistochemical studies of adhesive proteins showed enrichment of collagen types I, III, V, and VI, vitronectin, fibronectin, fibrinogen/fibrin, and thrombospondin in the atherosclerotic plaque. Laminin and collagen type IV were not enriched. von Willebrand Factor (vWF) was not present in the plaque. The pattern of increased platelet deposition in serial cross sections corresponded best with areas in which collagen types I and III were enriched, but there were also areas in the plaque where both collagens were enriched but no increased reactivity was seen. Inhibition of platelet adhesion with a large range of antibodies or specific inhibitors showed that vWF from plasma and collagen types I and/or III in the plaque were involved. Fibronectin from plasma and fibronectin, fibrinogen

  20. Rabbit hematology.

    PubMed

    Marshall, Kemba L

    2008-09-01

    Using laboratory animal medicine as an established resource, companion animal veterinarians have access to many physiologic and basic science studies that we can now merge with our clinical impressions. By working with reference laboratories, companion animal veterinarians are poised to accelerate our knowledge of the normal rabbit rapidly. The aim of this article is to discuss normal hematopoiesis and infectious and metabolic diseases that specifically target the hemolymphatic system. Additionally, photographic representation of cell types is provided.

  1. Experimental Plan for EDF Energy Creep Rabbit Graphite Irradiations- Rev. 2 (replaces Rev. 0 ORNL/TM/2013/49).

    SciTech Connect

    Burchell, Timothy D

    2014-07-01

    The experimental results obtained here will assist in the development and validation of future models of irradiation induced creep of graphite by providing the following data: Inert creep stain data from low to lifetime AGR fluence Inert creep-property data (especially CTE) from low to lifetime AGR fluence Effect of oxidation on creep modulus (by indirect comparison with experiment 1 and direct comparison with experiment 3 NB. Experiment 1 and 3 are not covered here) Data to develop a mechanistic understanding, including oAppropriate creep modulus (including pinning and high dose effects on structure) oInvestigation of CTE-creep strain behavior under inert conditions oInformation on the effect of applied stress/creep strain on crystallite orientation (requires XRD) oEffect of creep strain on micro-porosity (requires tomography & microscopy) This document describes the experimental work planned to meet the requirements of project technical specification [1] and EDF Energy requests for additional Pre-IE work. The PIE work is described in detail in this revision (Section 8 and 9).

  2. [Is regression of atherosclerotic plaque possible?

    PubMed

    Páramo, José A; Civeira, Fernando

    As it is well-known, a thrombus evolving into a disrupted/eroded atherosclerotic plaque causes most acute coronary syndromes. Plaque stabilization via reduction of the lipid core and/or thickening of the fibrous cap is one of the possible mechanisms accounted for the clinical benefits displayed by different anti-atherosclerotic strategies. The concept of plaque stabilization was developed to explain how lipid-lowering agents could decrease adverse coronary events without substantial modifications of the atherosclerotic lesion ('angiographic paradox'). A number of imaging modalities (vascular ultrasound and virtual histology, MRI, optical coherence tomography, positron tomography, etc.) are used for non-invasive assessment of atherosclerosis; most of them can identify plaque volume and composition beyond lumen stenosis. An 'aggressive' lipid-lowering strategy is able to reduce the plaque burden and the incidence of cardiovascular events; this may be attributable, at least in part, to plaque-stabilizing effects.

  3. Myeloperoxidase, a catalyst for lipoprotein oxidation, is expressed in human atherosclerotic lesions.

    PubMed

    Daugherty, A; Dunn, J L; Rateri, D L; Heinecke, J W

    1994-07-01

    Oxidatively modified lipoproteins have been implicated in atherogenesis, but the mechanisms that promote oxidation in vivo have not been identified. Myeloperoxidase, a heme protein secreted by activated macrophages, generates reactive intermediates that oxidize lipoproteins in vitro. To explore the potential role of myeloperoxidase in the development of atherosclerosis, we determined whether the enzyme was present in surgically excised human vascular tissue. In detergent extracts of atherosclerotic arteries subjected to Western blotting, a rabbit polyclonal antibody monospecific for myeloperoxidase detected a 56-kD protein, the predicted molecular mass of the heavy subunit. Both the immunoreactive protein and authentic myeloperoxidase bound to a lectin-affinity column; after elution with methyl mannoside their apparent molecular masses were indistinguishable by nondenaturing size-exclusion chromatography. Peroxidase activity in detergent extracts of atherosclerotic lesions likewise bound to a lectin column and eluted with methyl mannoside. Moreover, eluted peroxidase generated the cytotoxic oxidant hypochlorous acid (HOCl), indicating that enzymatically active myeloperoxidase was present in lesions. Patterns of immunostaining of arterial tissue with antihuman myeloperoxidase antibodies were similar to those produced by an antimacrophage antibody, and were especially prominent in the shoulder region of transitional lesions. Intense foci of myeloperoxidase immunostaining also appeared adjacent to cholesterol clefts in lipid-rich regions of advanced atherosclerotic lesions. These findings identify myeloperoxidase as a component of human vascular lesions. Because this heme protein can generate reactive species that damage lipids and proteins, myeloperoxidase may contribute to atherogenesis by catalyzing oxidative reactions in the vascular wall.

  4. Myeloperoxidase, a catalyst for lipoprotein oxidation, is expressed in human atherosclerotic lesions.

    PubMed Central

    Daugherty, A; Dunn, J L; Rateri, D L; Heinecke, J W

    1994-01-01

    Oxidatively modified lipoproteins have been implicated in atherogenesis, but the mechanisms that promote oxidation in vivo have not been identified. Myeloperoxidase, a heme protein secreted by activated macrophages, generates reactive intermediates that oxidize lipoproteins in vitro. To explore the potential role of myeloperoxidase in the development of atherosclerosis, we determined whether the enzyme was present in surgically excised human vascular tissue. In detergent extracts of atherosclerotic arteries subjected to Western blotting, a rabbit polyclonal antibody monospecific for myeloperoxidase detected a 56-kD protein, the predicted molecular mass of the heavy subunit. Both the immunoreactive protein and authentic myeloperoxidase bound to a lectin-affinity column; after elution with methyl mannoside their apparent molecular masses were indistinguishable by nondenaturing size-exclusion chromatography. Peroxidase activity in detergent extracts of atherosclerotic lesions likewise bound to a lectin column and eluted with methyl mannoside. Moreover, eluted peroxidase generated the cytotoxic oxidant hypochlorous acid (HOCl), indicating that enzymatically active myeloperoxidase was present in lesions. Patterns of immunostaining of arterial tissue with antihuman myeloperoxidase antibodies were similar to those produced by an antimacrophage antibody, and were especially prominent in the shoulder region of transitional lesions. Intense foci of myeloperoxidase immunostaining also appeared adjacent to cholesterol clefts in lipid-rich regions of advanced atherosclerotic lesions. These findings identify myeloperoxidase as a component of human vascular lesions. Because this heme protein can generate reactive species that damage lipids and proteins, myeloperoxidase may contribute to atherogenesis by catalyzing oxidative reactions in the vascular wall. Images PMID:8040285

  5. Relationship of MMP-14 and TIMP-3 Expression with Macrophage Activation and Human Atherosclerotic Plaque Vulnerability

    PubMed Central

    Johnson, Jason L.; Jenkins, Nicholas P.; Huang, Wei-Chun; Sala-Newby, Graciela B.; Scholtes, Vincent P. W.; Moll, Frans L.; Pasterkamp, Gerard; Newby, Andrew C.

    2014-01-01

    Matrix metalloproteinase-14 (MMP-14) promotes vulnerable plaque morphology in mice, whereas tissue inhibitor of metalloproteinases-3 (TIMP-3) overexpression is protective. MMP-14hi  TIMP-3lo rabbit foam cells are more invasive and more prone to apoptosis than MMP-14lo  TIMP-3hi cells. We investigated the implications of these findings for human atherosclerosis. In vitro generated macrophages and foam-cell macrophages, together with atherosclerotic plaques characterised as unstable or stable, were examined for expression of MMP-14, TIMP-3, and inflammatory markers. Proinflammatory stimuli increased MMP-14 and decreased TIMP-3 mRNA and protein expression in human macrophages. However, conversion to foam-cells with oxidized LDL increased MMP-14 and decreased TIMP-3 protein, independently of inflammatory mediators and partly through posttranscriptional mechanisms. Within atherosclerotic plaques, MMP-14 was prominent in foam-cells with either pro- or anti-inflammatory macrophage markers, whereas TIMP-3 was present in less foamy macrophages and colocalised with CD206. MMP-14 positive macrophages were more abundant whereas TIMP-3 positive macrophages were less abundant in plaques histologically designated as rupture prone. We conclude that foam-cells characterised by high MMP-14 and low TIMP-3 expression are prevalent in rupture-prone atherosclerotic plaques, independent of pro- or anti-inflammatory activation. Therefore reducing MMP-14 activity and increasing that of TIMP-3 could be valid therapeutic approaches to reduce plaque rupture and myocardial infarction. PMID:25301980

  6. The Effect of a Polyvalent Antivenom on the Serum Venom Antigen Levels of Naja sputatrix (Javan Spitting Cobra) Venom in Experimentally Envenomed Rabbits.

    PubMed

    Yap, Michelle Khai Khun; Tan, Nget Hong; Sim, Si Mui; Fung, Shin Yee; Tan, Choo Hock

    2015-10-01

    The treatment protocol of antivenom in snake envenomation remains largely empirical, partly due to the insufficient knowledge of the pharmacokinetics of snake venoms and the effects of antivenoms on the blood venom levels in victims. In this study, we investigated the effect of a polyvalent antivenom on the serum venom antigen levels of Naja sputatrix (Javan spitting cobra) venom in experimentally envenomed rabbits. Intravenous infusion of 4 ml of Neuro Polyvalent Snake Antivenom [NPAV, F(ab')2 ] at 1 hr after envenomation caused a sharp decline of the serum venom antigen levels, followed by transient resurgence an hour later. The venom antigen resurgence was unlikely to be due to the mismatch of pharmacokinetics between the F(ab')2 and venom antigens, as the terminal half-life and volume of distribution of the F(ab')2 in serum were comparable to that of venom antigens (p > 0.05). Infusion of an additional 2 ml of NPAV was able to prevent resurgence of the serum venom antigen level, resulting in a substantial decrease (67.1%) of the total amount of circulating venom antigens over time course of envenomation. Our results showed that the neutralization potency of NPAV determined by neutralization assay in mice may not be an adequate indicator of its capability to modulate venom kinetics in relation to its in vivo efficacy to neutralize venom toxicity. The findings also support the recommendation of giving high initial dose of NPAV in cobra envenomation, with repeated doses as clinically indicated in the presence of rebound antigenemia and symptom recurrence.

  7. The efficacy of N-2-butyl cyanoacrylate in the fixation of nasal septum to the anterior nasal spine in rabbits: experimental study.

    PubMed

    Alkan, Seyhan; Dadaş, Burhan; Celik, Deniz; Coskun, Berna Uslu; Yilmaz, Fahrettin; Başak, Tülay

    2007-12-01

    In nasal septal surgery, fixing the caudal portion of the nasal septum to the anterior nasal spine is difficult with the present techniques. N-2-butyl cyanoacrylate is a form of cyanoacrylate which is bioabsorbable and biocompatible. The feasibility and efficacy of the compound, which is easy to apply to the tissues, for the above purpose is investigated in this experimental study. Fourteen New Zealand rabbits were included in the study. The nasal septum was exposed with the open approach (transcolumellar). In the study group (n=10), the septum was detached from the nasal floor and attached to a point 3 mm lateral to the nasal spine on the right side, using 2-butyl cyanoacrylate. In control group (n=4) it was deviated 3 mm to the right side and left for spontaneous healing without using any fixation method. Beginning on the third postoperative week, one animal was sacrificed under general anesthesia, every week in the study group and every third week in the control group, and the septum was analysed. Foreign body reaction, histotoxicity, and the structure of the regenerative tissue in the junction of bone and cartilage were analysed with histopathology. The success of stabilization in the study group, where the septum was attached with N-2-butyl cyanoacrylate, was significantly superior to the control group where no fixation method was used (P<0.05). Histopathologically, there were no differences between the two groups with respect to foreign body reaction, histotoxicity, and the tissue that formed between the bone and cartilage (P>0.05). This study demonstrated that N-2-Butyl cyanoacrylate was successful in the fixation of the caudal edge of the nasal septum to the anterior nasal spine. No serious infections, foreign body reaction, necrosis or histotoxicity were observed.

  8. Mesenchymal Stem Cells Stabilize Atherosclerotic Vulnerable Plaque by Anti-Inflammatory Properties

    PubMed Central

    Wang, Shuang-shuang; Hu, Si-wang; Zhang, Qing-hua; Xia, Ai-xiang

    2015-01-01

    Background and objectives Formation and progression of atherosclerotic vulnerable plaque (VP) is the primary cause of many cardio-cerebrovascular diseases such as acute coronary syndrome and stroke. It has been reported that bone marrow mesenchymal stem cells (MSC) exhibit protective effects against many kinds of diseases including myocardial infarction. Here, we examined the effects of intravenous MSC infusion on a VP model and provide novel evidence of its influence as a therapy in this animal disease model. Subjects and methods Thirty healthy male New Zealand white rabbits were randomly divided into a MSC, VP or stable plaque (SP) group (n = 10/group) and received high fat diet and cold-induced common carotid artery intimal injury with liquid nitrogen to form atherosclerotic plaques. Serum hs-CRP, TNF-α, IL-6 and IL-10 levels were measured by ELISA at 1, 2, 3, 7, 14, 21 and 28 days after MSC transplantation. The animals were sacrificed at 4 weeks after MSC transplantation. Lesions in the right common carotid were observed using H&E and Masson staining, and the fibrous cap/lipid core ratio of atherosclerotic plaques were calculated. The expression of nuclear factor κB (NF-κB) and matrix metalloproteinase 1, 2, 9 (MMP-1,2,9) in the plaque were detected using immunohistochemistry, and apoptotic cells in the plaques were detected by TUNEL. In addition, the level of TNF-α stimulated gene/protein 6 (TSG-6) mRNA and protein were measured by quantitative Real-Time PCR and Western blotting, respectively. Results Two rabbits in the VP group died of lung infection and cerebral infarction respectively at 1 week after plaque injury by liquid nitrogen. Both H&E and Masson staining revealed that the plaques from the SP and MSC groups had more stable morphological structure and a larger fibrous cap/lipid core ratio than the VP group. Serum hs-CRP, TNF-α and IL-6 were significantly down-regulated, whereas IL-10 was significantly up-regulated in the MSC group compared with

  9. RABBIT POX

    PubMed Central

    Rosahn, Paul D.; Hu, Ch'uan-K'uei

    1935-01-01

    Observations on an epidemic of rabbit pox occurring in an isolated animal room during the winter of 1933–34 are reported. The clinical manifestations, consisting of a generalized papular eruption involving the skin and mucous membranes, together with blepharitis, ophthalmia, nasal discharge and lymphadenopathy were essentially similar to those noted in a pox epidemic of the previous year. This was true in general also of the pathological findings except that vacuolization, local necrosis and vesicle formation were seen in the epidermis, while in the previous year the microscopic pathology in the skin was confined to the corium. Evidence was presented indicating that the infection can be transmitted through the medium of a personal carrier, and that transmission in this manner can occur during the incubation period or before a definite diagnosis is possible. The findings also demonstrated that the etiological agents responsible for the disease reported here and that of the previous year were immunologically related, and that the immunity in recovered animals effectively persisted during the entire period for which data are available, 9 to 12 months. It appeared also that young animals suckling an immune doe were more refractory to the development of the lesions of rabbit pox than were the young of susceptible does. PMID:19870418

  10. Alteration of antibodies against the fifth-stage larvae and changes in brain magnetic resonance images in experimentally infected rabbits with Angiostrongylus cantonensis.

    PubMed

    Wang, Lian-Chen; Wan, Yung-Liang

    2004-10-01

    Magnetic resonance (MR) imaging has been suggested to be helpful in delineating the lesions during the acute phase of angiostrongyliasis caused by Angiostrongylus cantonensis. In this study, antibody titers in serum samples of 3 rabbits were determined by enzyme-linked immunosorbent assay, and brain MR images were obtained from 6 rabbits. The antibody titer elevated rapidly in the first 4 wk postinfection (PI) before reaching a plateau. However, suspicious changes in brain MR images near the left lateral ventricle and hippocampus were found only in 1 rabbit on day 28 PI. These findings indicate that immunologic responses in the central nervous system at the early stage of angiostrongyliasis are not sufficient to be observed by image studies.

  11. Pharmacokinetics and atherosclerotic lesions targeting effects of tanshinone IIA discoidal and spherical biomimetic high density lipoproteins.

    PubMed

    Zhang, Wenli; He, Hongliang; Liu, Jianping; Wang, Ji; Zhang, Suyang; Zhang, Shuangshuang; Wu, Zimei

    2013-01-01

    High density lipoproteins (HDL) have been successfully reconstructed to deliver a large number of lipophilic drugs. Here, discoidal and spherical recombinant HDL loaded with cardiovascular drug tanshinone IIA (TA) were constructed (TA-d-rHDL and TA-s-rHDL), respectively. And next their in vitro physiochemical and biomimetic properties were characterized. Furthermore, pharmacokinetics, atherosclerotic lesions targeting effects and antiatherogenic efficacies were elaborately performed and compared in atherosclerotic New Zealand White (NZW) rabbits. In vitro characterizations results showed that both TA-d-rHDL and TA-s-rHDL had nano-size diameter, high entrapment efficiency (EE) and drug-loading capacity (DL). Additionally, similar to their native counterparts, TA-d-rHDL maintained remodeling behaviors induced by lecithin cholesterol acyltransferase (LCAT), and TA leaked during remodeling behaviors. Pharmacokinetic studies manifested that both TA-d-rHDL and TA-s-rHDL markedly improved pharmacokinetic behaviors of TA in vivo. Ex vivo imaging demonstrated that both d-rHDL and s-rHDL bound more avidly to atherosclerotic lesions than to normal vessel walls, and s-rHDL had better targeting effect than d-rHDL. Pharmacodynamic tests illustrated that both TA-d-rHDL and TA-s-rHDL had much stronger antiatherogenic efficacies than conventional TA nanostructured lipid carriers (TA-NLC), TA liposomes (TA-L) and commercially available preparation Sulfotanshinone Sodium Injection (SSI). Moreover, TA-s-rHDL had more potent antiatherogenic efficacies than TA-d-rHDL. Collectively our studies indicated that rHDL could be exploited as potential delivery vehicles of TA targeting atherosclerotic lesions as well as synergistically improving efficacies, especially for s-rHDL. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. N-terminal telopeptides of type I collagen and bone mineral density for early diagnosis of nonunion: An experimental study in rabbits.

    PubMed

    Lin, Jian-Ping; Shi, Zhan-Jun; Shen, Ning-Jiang; Wang, Jian; Li, Zao-Min; Xiao, Jun

    2016-01-01

    The diagnosis and treatment of bone nonunion have been studied extensively. Diagnosis and treatment of nonunion are mainly performed based on the interpretation of clinico-radiographic findings, which depend on the clinician's experience and the degree of bone callus formation during the fracture-healing process. However, resolution may be compromised when the bone mineral content is <25%. A feasible method of monitoring bone-healing is therefore needed. We monitored a rabbit model of bone nonunion by regular radiographic examinations, QCT detection, and biomarker concentrations. Twenty purebred New Zealand rabbits (10 male and 10 female, 5-6 months of age, 2.5-3.0 kg) were divided into bone defect Group (I) that 10 left radius bones underwent resection of 1.5 cm of mid-radius bone and bone fracture Group (II) that another 10 left radius bones underwent only mid-radius fracture. Quantitative computed tomography detection of bone mineral density (BMD) and serum markers of bone formation (osteocalcin [OC], bone-specific alkaline phosphatase) and bone resorption (C- and N-terminal telopeptides of type I collagen (NTX) and tartrate-resistant acid phosphatase 5b) were assayed. There are twenty rabbits (10 male and 10 females). The age was 5-6 months weighing 2.5-3.0 kg). The defect was created in middle 1/3 radius in 10 rabbits and fracture was created in middle 1/3 radius of 10 rabbits. BMD and NTX concentrations were significantly lower at 5 weeks postoperatively compared to the preoperative values and were significantly different between the two groups. OC showed no significant difference before and after surgery. BMD and NTX concentrations may be useful for early detection of bone nonunion in rabbits.

  13. Icaritin Inhibits Collagen Degradation-Related Factors and Facilitates Collagen Accumulation in Atherosclerotic Lesions: A Potential Action for Plaque Stabilization.

    PubMed

    Zhang, Zong-Kang; Li, Jie; Yan, De-Xin; Leung, Wing-Nang; Zhang, Bao-Ting

    2016-01-28

    Most acute coronary syndromes result from rupture of vulnerable atherosclerotic plaques. The collagen content of plaques may critically affect plaque stability. This study tested whether Icaritin (ICT), an intestinal metabolite of Epimedium-derived flavonoids, could alter the collagen synthesis/degradation balance in atherosclerotic lesions. Rabbits were fed with an atherogenic diet for four months. Oral administration of ICT (10 mg·kg(-1)·day(-1)) was started after two months of an atherogenic diet and lasted for two months. The collagen degradation-related parameters, including macrophages accumulation, content and activity of interstitial collagenase-1 (MMP-1), and the collagen synthesis-related parameters, including amount and distribution of smooth muscle cells (SMC) and collagen mRNA/protein levels, were evaluated in the aorta. ICT reduced plasma lipid levels, inhibited macrophage accumulation, lowered MMP-1 mRNA and protein expression, and suppressed proteolytic activity of pro-MMP-1 and MMP-1 in the aorta. ICT changed the distribution of the SMCs towards the fibrous cap of lesions without increasing the amount of SMCs. Higher collagen protein content in lesions and aorta homogenates was observed with ICT treatment compared with the atherogenic diet only, without altered collagen mRNA level. These results suggest that ICT could inhibit the collagen degradation-related factors and facilitate collagen accumulation in atherosclerotic lesions, indicating a new potential of ICT in atherosclerotic plaques.

  14. Icaritin Inhibits Collagen Degradation-Related Factors and Facilitates Collagen Accumulation in Atherosclerotic Lesions: A Potential Action for Plaque Stabilization

    PubMed Central

    Zhang, Zong-Kang; Li, Jie; Yan, De-Xin; Leung, Wing-Nang; Zhang, Bao-Ting

    2016-01-01

    Most acute coronary syndromes result from rupture of vulnerable atherosclerotic plaques. The collagen content of plaques may critically affect plaque stability. This study tested whether Icaritin (ICT), an intestinal metabolite of Epimedium-derived flavonoids, could alter the collagen synthesis/degradation balance in atherosclerotic lesions. Rabbits were fed with an atherogenic diet for four months. Oral administration of ICT (10 mg·kg−1·day−1) was started after two months of an atherogenic diet and lasted for two months. The collagen degradation-related parameters, including macrophages accumulation, content and activity of interstitial collagenase-1 (MMP-1), and the collagen synthesis-related parameters, including amount and distribution of smooth muscle cells (SMC) and collagen mRNA/protein levels, were evaluated in the aorta. ICT reduced plasma lipid levels, inhibited macrophage accumulation, lowered MMP-1 mRNA and protein expression, and suppressed proteolytic activity of pro-MMP-1 and MMP-1 in the aorta. ICT changed the distribution of the SMCs towards the fibrous cap of lesions without increasing the amount of SMCs. Higher collagen protein content in lesions and aorta homogenates was observed with ICT treatment compared with the atherogenic diet only, without altered collagen mRNA level. These results suggest that ICT could inhibit the collagen degradation-related factors and facilitate collagen accumulation in atherosclerotic lesions, indicating a new potential of ICT in atherosclerotic plaques. PMID:26828485

  15. Mapping elasticity moduli of atherosclerotic plaque in situ via atomic force microscopy.

    PubMed

    Tracqui, Philippe; Broisat, Alexis; Toczek, Jackub; Mesnier, Nicolas; Ohayon, Jacques; Riou, Laurent

    2011-04-01

    Several studies have suggested that evolving mechanical stresses and strains drive atherosclerotic plaque development and vulnerability. Especially, stress distribution in the plaque fibrous capsule is an important determinant for the risk of vulnerable plaque rupture. Knowledge of the stiffness of atherosclerotic plaque components is therefore of critical importance. In this work, force mapping experiments using atomic force microscopy (AFM) were conducted in apolipoprotein E-deficient (ApoE(-/-)) mouse, which represents the most widely used experimental model for studying mechanisms underlying the development of atherosclerotic lesions. To obtain the elastic material properties of fibrous caps and lipidic cores of atherosclerotic plaques, serial cross-sections of aortic arch lesions were probed at different sites. Atherosclerotic plaque sub-structures were subdivided into cellular fibrotic, hypocellular fibrotic and lipidic rich areas according to histological staining. Hertz's contact mechanics were used to determine elasticity (Young's) moduli that were related to the underlying histological plaque structure. Cellular fibrotic regions exhibit a mean Young modulus of 10.4±5.7kPa. Hypocellular fibrous caps were almost six-times stiffer, with average modulus value of 59.4±47.4kPa, locally rising up to ∼250kPa. Lipid rich areas exhibit a rather large range of Young's moduli, with average value of 5.5±3.5kPa. Such precise quantification of plaque stiffness heterogeneity will allow investigators to have prospectively a better monitoring of atherosclerotic disease evolution, including arterial wall remodeling and plaque rupture, in response to mechanical constraints imposed by vascular shear stress and blood pressure.

  16. Functional Heterogeneity of Nadph Oxidases in Atherosclerotic and Aneurysmal Diseases

    PubMed Central

    Kigawa, Yasuyoshi; Lei, Xiao-Feng; Kim-Kaneyama, Joo-ri; Miyazaki, Akira

    2017-01-01

    NADPH oxidases (NOX) are enzymes that catalyze the production of reactive oxygen species (ROS). Four species of NOX catalytic homologs (NOX1, NOX2, NOX4, and NOX5) are reportedly expressed in vascular tissues. The pro-atherogenic roles of NOX1, NOX2, and their organizer protein p47phox were manifested, and it was noted that the hydrogen peroxide-generating enzyme NOX4 possesses atheroprotective effects. Loss of NOX1 or p47phox appears to ameliorate murine aortic dissection and subsequent aneurysmal diseases; in contrast, the ablation of NOX2 exacerbates the aneurysmal diseases. It is possible that the loss of NOX2 activates inflammatory cascades in macrophages in the lesions. Roles of NOX5 in vascular functions are currently undetermined, owing to the absence of this enzyme in rodents and the limitation of the experimental procedure. Thus, it is possible that the NOX family of enzymes exhibits heterogeneity in the atherosclerotic diseases. In this aspect, subtype-selective NOX inhibitor may be promising when NOX systems serve as a molecular target for atherosclerotic and aneurysmal diseases. PMID:27476665

  17. Is Limited Prehospital Resuscitation with Plasma More Beneficial than Using a Synthetic Colloid? An Experimental Study in Rabbits with Parenchymal Bleeding

    DTIC Science & Technology

    2015-04-01

    Holcomb JB. Effects of synthetic versus natural colloid resuscitation on inducing dilutional coagulopathy and increasing hemorrhage in rabbits. J Trauma...directly addressing the early coagulopathy of trauma. J Trauma. 2007;62(2):307Y310. 27. Shuja F, Shults C, Duggan M, Tabbara M, Butt MU, Fischer TH

  18. Altered glucose metabolism and hypoxic response in alloxan-induced diabetic atherosclerosis in rabbits.

    PubMed

    Matsuura, Yunosuke; Yamashita, Atsushi; Zhao, Yan; Iwakiri, Takashi; Yamasaki, Kazuaki; Sugita, Chihiro; Koshimoto, Chihiro; Kitamura, Kazuo; Kawai, Keiichi; Tamaki, Nagara; Zhao, Songji; Kuge, Yuji; Asada, Yujiro

    2017-01-01

    Diabetes mellitus accelerates atherosclerosis that causes most cardiovascular events. Several metabolic pathways are considered to contribute to the development of atherosclerosis, but comprehensive metabolic alterations to atherosclerotic arterial cells remain unknown. The present study investigated metabolic changes and their relationship to vascular histopathological changes in the atherosclerotic arteries of rabbits with alloxan-induced diabetes. Diabetic atherosclerosis was induced in rabbit ilio-femoral arteries by injecting alloxan (100 mg/kg), injuring the arteries using a balloon, and feeding with a 0.5% cholesterol diet. We histologically assessed the atherosclerotic lesion development, cellular content, pimonidazole positive-hypoxic area, the nuclear localization of hypoxia-inducible factor-1α, and apoptosis. We evaluated comprehensive arterial metabolism by performing metabolomic analyses using capillary electrophoresis-time of flight mass spectrometry. We evaluated glucose uptake and its relationship to vascular hypoxia using 18F-fluorodeoxyglucose and pimonidazole. Plaque burden, macrophage content, and hypoxic areas were more prevalent in arteries with diabetic, than non-diabetic atherosclerosis. Metabolomic analyses highlighted 12 metabolites that were significantly altered between diabetic and non-diabetic atherosclerosis. A half of them were associated with glycolysis metabolites, and their levels were decreased in diabetic atherosclerosis. The uptake of glucose evaluated as 18F-fluorodeoxyglucose in atherosclerotic lesions increased according to increased macrophage content or hypoxic areas in non-diabetic, but not diabetic rabbits. Despite profound hypoxic areas, the nuclear localization of hypoxia-inducible factor-1α decreased and the number of apoptotic cells increased in diabetic atherosclerotic lesions. Altered glycolysis metabolism and an impaired response to hypoxia in atherosclerotic lesions under conditions of insulin

  19. Evaluation of implant osseointegration with different regeneration techniques in the treatment of bone defects around implants: an experimental study in a rabbit model.

    PubMed

    Guerra, Isabel; Morais Branco, Fernando; Vasconcelos, Mário; Afonso, Américo; Figueiral, Helena; Zita, Raquel

    2011-03-01

    The aim of this study was to evaluate the osseointegration of implants placed in areas with artificially created bone defects, using three bone regeneration techniques. The experimental model was the rabbit femur (16), where bone defects were created and implants were placed. The peri-implant bone defects were filled with a deproteinized bovine bone mineral, NuOss™ (N), NuOss™ combined with plasma rich in growth factors (PRGF) (N+PRGF), NuOss™ covered by an RCM(6) membrane (N+M), or remained unfilled (control group [C]). After 4 and 8 weeks, the animals were euthanized and bone tissue blocks with the implants and the surrounding bone tissue were removed and processed according to a histological protocol for hard tissues on non-decalcified ground sections. The samples were studied by light and electron scanning microscopy, histometric analysis was performed to assess the percentage of bone in direct contact with the implant surface and a statistical analysis of the results was performed. In the samples analyzed 4 weeks after implantation, the percentage of bone tissue in direct contact with the implant surface for the four groups were 57.66±24.39% (N), 58.62±20.37% (N+PRGF), 70.82±20.34 % (N+M) and 33.07±5.49% (C). In the samples with 8 weeks of implantation time, the percentage of bone in direct contact was 63.35±27.69% (N), 58.42±24.77% (N+PRGF), 78.02±15.13% (N+M) and 40.28±27.32% (C). In terms of the percentage of bone contact, groups N and N+M presented statistically significant differences from group C in the 4-week trial test (P<0.05; ANOVA). For the 8-week results, only group N+M showed statistically significant differences when compared with group C (P<0.05; ANOVA). In conclusion, the NuOss™ granules/RCM(6) membrane combination presented a percentage of bone contact with the implant surface statistically greater than in the other groups. © 2010 John Wiley & Sons A/S.

  20. Intradiscal pressure measurements in normal discs, compressed discs and compressed discs treated with axial posterior disc distraction: an experimental study on the rabbit lumbar spine model.

    PubMed

    Guehring, Thorsten; Unglaub, Frank; Lorenz, Helga; Omlor, Georg; Wilke, Hans-Joachim; Kroeber, Markus W

    2006-05-01

    Intervertebral disc (IVD) pressure measurement is an appropriate method for characterizing spinal loading conditions. However, there is no human or animal model that provides sufficient IVD pressure data. The aim of our study was to establish physiological pressure values in the rabbit lumbar spine and to determine whether temporary external disc compression and distraction were associated with pressure changes. Measurements were done using a microstructure-based fibreoptic sensor. Data were collected in five control rabbits (N, measurement lying prone at segment L3/4 at day 28), five rabbits with 28 days of axial compression (C, measurement at day 28) and three rabbits with 28 days of axial compression and following 28 days of axial distraction (D, measurement at day 56). Disc compression and distraction was verified by disc height in lateral radiographs. The controls (N) showed a level-related range between 0.25 MPa-0.45 MPa. The IVD pressure was highest at level L3/4 (0.42 MPa; range 0.38-0.45) with a decrease in both cranial and caudal adjacent segments. The result for C was a significant decrease in IVD pressure (0.31 MPa) when compared with controls (P=0.009). D showed slightly higher median IVD pressure (0.32 MPa) compared to C, but significantly lower levels when compared with N (P=0.037). Our results indicate a high range of physiological IVD pressure at different levels of the lumbar rabbit spine. Temporary disc compression reduces pressure when compared with controls. These data support the hypothesis that temporary external compression leads to moderate disc degeneration as a result of degradation of water-binding disc matrix or affected active pumping mechanisms of nutrients into the disc. A stabilization of IVD pressure in discs treated with temporary distraction was observed.

  1. Novel Calicivirus Identified in Rabbits, Michigan, USA

    PubMed Central

    Wise, Annabel G.; Bolin, Steven R.; Mullaney, Thomas P.; Kiupel, Matti; Maes, Roger K.

    2009-01-01

    We report a disease outbreak in a Michigan rabbitry of a rabbit calicivirus distinct from the foreign animal disease agent, rabbit hemorrhagic disease virus (RHDV). The novel virus has been designated Michigan rabbit calicivirus (MRCV). Caliciviruses of the Lagovirus genus other than RHDV have not been described in US rabbit populations. The case-fatality rate was 32.5% (65/200). Clinical signs included hemorrhage and sudden death, with hepatic necrosis. Analysis of viral RNA sequence from >95% of the viral genome showed an average similarity of 79% with RHDV. Similarity of the predicted MRCV capsid amino acid sequence ranged from 89.8% to 91.3%, much lower than the 98% amino acid similarity between RHDV strains. Experimentally infected rabbits lacked clinical disease, but MRCV was detected in tissues by PCR. We propose that MRCV primarily causes subclinical infection but may induce overt RHD-like disease under certain field conditions. PMID:19961675

  2. Catalpol ameliorates diabetic atherosclerosis in diabetic rabbits

    PubMed Central

    Liu, Jiang-Yue; Zheng, Chen-Zhao; Hao, Xin-Ping; Zhang, Dai-Juan; Mao, An-Wei; Yuan, Ping

    2016-01-01

    Catalpol, isolated from the roots of Rehmanniaglutinosa, Chinese foxglove, is an iridoid glycoside with antioxidant, anti-inflammatory and anti-hyperglycemic agent. The present study was to investigate the effects of catalpol on diabetic atherosclerosis in alloxan-induced diabetic rabbits. Diabetes was induced in rabbits by a hyperlipidemic diet and intravenous injection of alloxan (100 mg/kg). Rabbits were treated for 12 weeks. The fasting blood glucose, insulin, homeostasis model of insulin resistance, total cholesterol and triglyceride were measured. The thoracic aorta was excised for histology. The plasma and vascular changes including some markers of oxidative stress, inflammatory cytokines and fibrosis factors were examined. Plasma levels of fasting blood glucose, insulin and homeostasis model of insulin resistance were significantly decreased in catalpol group. Catalpol treatment ameliorated diabetic atherosclerosis in diabetic rabbits as demonstrated by significantly inhibited neointimal hyperplasia and macrophages recruitment. Catalpol treatment also enhanced the activities of superoxide dismutase, glutathione peroxidase, and increased the plasma levels of total antioxidant status, meanwhile reduced the levels of malondialdehyde, protein carbonyl groups and advanced glycation end product. Furthermore, catalpol also reduced circulating levels of tumor necrosis factor-α, monocyte chemotactic protein-1 and vascular cell adhesion molecule-1. Catalpol also decreased transforming growth factor-β1 and collagen IV mRNA and protein expressions in the vessels. Catalpol exerts an ameliorative effect on atherosclerotic lesion in alloxan-induced diabetic rabbits. The possible mechanisms may be related to inhibition of oxidative stress inflammatory response and anti-fibrosis and reduced aggregation of extracellular matrix. PMID:27830011

  3. Inhibiting macrophage proliferation suppresses atherosclerotic plaque inflammation.

    PubMed

    Tang, Jun; Lobatto, Mark E; Hassing, Laurien; van der Staay, Susanne; van Rijs, Sarian M; Calcagno, Claudia; Braza, Mounia S; Baxter, Samantha; Fay, Francois; Sanchez-Gaytan, Brenda L; Duivenvoorden, Raphaël; Sager, Hendrik; Astudillo, Yaritzy M; Leong, Wei; Ramachandran, Sarayu; Storm, Gert; Pérez-Medina, Carlos; Reiner, Thomas; Cormode, David P; Strijkers, Gustav J; Stroes, Erik S G; Swirski, Filip K; Nahrendorf, Matthias; Fisher, Edward A; Fayad, Zahi A; Mulder, Willem J M

    2015-04-01

    Inflammation drives atherosclerotic plaque progression and rupture, and is a compelling therapeutic target. Consequently, attenuating inflammation by reducing local macrophage accumulation is an appealing approach. This can potentially be accomplished by either blocking blood monocyte recruitment to the plaque or increasing macrophage apoptosis and emigration. Because macrophage proliferation was recently shown to dominate macrophage accumulation in advanced plaques, locally inhibiting macrophage proliferation may reduce plaque inflammation and produce long-term therapeutic benefits. To test this hypothesis, we used nanoparticle-based delivery of simvastatin to inhibit plaque macrophage proliferation in apolipoprotein E deficient mice (Apoe(-/-) ) with advanced atherosclerotic plaques. This resulted in rapid reduction of plaque inflammation and favorable phenotype remodeling. We then combined this short-term nanoparticle intervention with an eight-week oral statin treatment, and this regimen rapidly reduced and continuously suppressed plaque inflammation. Our results demonstrate that pharmacologically inhibiting local macrophage proliferation can effectively treat inflammation in atherosclerosis.

  4. Inhibiting macrophage proliferation suppresses atherosclerotic plaque inflammation

    PubMed Central

    Tang, Jun; Lobatto, Mark E.; Hassing, Laurien; van der Staay, Susanne; van Rijs, Sarian M.; Calcagno, Claudia; Braza, Mounia S.; Baxter, Samantha; Fay, Francois; Sanchez-Gaytan, Brenda L.; Duivenvoorden, Raphaël; Sager, Hendrik B.; Astudillo, Yaritzy M.; Leong, Wei; Ramachandran, Sarayu; Storm, Gert; Pérez-Medina, Carlos; Reiner, Thomas; Cormode, David P.; Strijkers, Gustav J.; Stroes, Erik S. G.; Swirski, Filip K.; Nahrendorf, Matthias; Fisher, Edward A.; Fayad, Zahi A.; Mulder, Willem J. M.

    2015-01-01

    Inflammation drives atherosclerotic plaque progression and rupture, and is a compelling therapeutic target. Consequently, attenuating inflammation by reducing local macrophage accumulation is an appealing approach. This can potentially be accomplished by either blocking blood monocyte recruitment to the plaque or increasing macrophage apoptosis and emigration. Because macrophage proliferation was recently shown to dominate macrophage accumulation in advanced plaques, locally inhibiting macrophage proliferation may reduce plaque inflammation and produce long-term therapeutic benefits. To test this hypothesis, we used nanoparticle-based delivery of simvastatin to inhibit plaque macrophage proliferation in apolipoprotein E–deficient mice (Apoe−/−) with advanced atherosclerotic plaques. This resulted in the rapid reduction of plaque inflammation and favorable phenotype remodeling. We then combined this short-term nanoparticle intervention with an 8-week oral statin treatment, and this regimen rapidly reduced and continuously suppressed plaque inflammation. Our results demonstrate that pharmacologically inhibiting local macrophage proliferation can effectively treat inflammation in atherosclerosis. PMID:26295063

  5. Selective removal of cholesteryl ester in atherosclerotic plaque by nanosecond pulsed laser at 5.75 μm for less-invasive laser angioplasty

    NASA Astrophysics Data System (ADS)

    Ishii, Katsunori; Tsukimoto, Hideki; Hazama, Hisanao; Awazu, Kunio

    2009-02-01

    Laser angioplasty, for example XeCl excimer laser coronary angioplasty (ELCA), has gained more attention for the treatment of serious stenosis blocked by plaque. Low degrees of thermal damage after ablation of atherosclerotic plaques have been achieved by ELCA. However, the large number of risks associated with the procedure, for example, dissections or perforations of the coronary arteries limits its application. A laser treatment technique with high ablation efficiency but low arterial wall injury is desirable. Mid-infrared laser with a wavelength of 5.75 µm is selectively well absorbed in C=O stretching vibration mode of ester bonds in cholesteryl ester. The purpose of this study is to determine the effectiveness of nanosecond pulsed laser at 5.75 µm irradiation for atherosclerotic plaques. We made a study on the irradiation effect to atherosclerotic plaques in tunica intima in a wet condition. In this study, we used a mid-infrared tunable solid-state laser which is operated by difference-frequency generation, with a wavelength of 5.75 µm, a pulse width of 5 ns and a pulse duration of 10 Hz as a treatment light source, and a thoracic aorta of WHHLMI rabbit as an atherosclerosis model. As a result, less-invasive interaction parameters for removing atherosclerotic plaques were confirmed. This study shows that the nanosecond pulsed laser irradiation at 5.75 µm is a powerful tool for selective and less-invasive treatment of atherosclerotic plaques.

  6. Inelasticity of human carotid atherosclerotic plaque.

    PubMed

    Maher, Eoghan; Creane, Arthur; Sultan, Sherif; Hynes, Niamh; Lally, Caitríona; Kelly, Daniel J

    2011-09-01

    Little mechanical test data exists regarding the inelastic behavior of atherosclerotic plaques. As a result finite element (FE) models of stenting procedures commonly use hyperelastic material models to describe the soft tissue response thus limiting the accuracy of the model to the expansion stage of stent implantation and leave them unable to predict the lumen gain. In this study, cyclic mechanical tests were performed to characterize the inelastic behavior of fresh human carotid atherosclerotic plaque tissue due to radial compressive loading. Plaques were classified clinically as either mixed (M), calcified (Ca), or echolucent (E). An approximately linear increase in the plastic deformation was observed with increases in the peak applied strain for all plaque types. While calcified plaques generally appeared stiffest, it was observed that the clinical classification of plaques had no significant effect on the magnitude of permanent deformation on unloading. The test data was characterized using a constitutive model that accounts for both permanent deformation and stress softening to describe the compressive plaque behavior on unloading. Material constants are reported for individual plaques as well as mean values for each plaque classification. This data can be considered as a first step in characterizing the inelastic behavior of atherosclerotic plaques and could be used in combination with future mechanical data to improve the predictive capabilities of FE models of angioplasty and stenting procedures particularly in relation to lumen gain.

  7. Viral infections of rabbits.

    PubMed

    Kerr, Peter J; Donnelly, Thomas M

    2013-05-01

    Viral diseases of rabbits have been used historically to study oncogenesis (e.g. rabbit fibroma virus, cottontail rabbit papillomavirus) and biologically to control feral rabbit populations (e.g. myxoma virus). However, clinicians seeing pet rabbits in North America infrequently encounter viral diseases although myxomatosis may be seen occasionally. The situation is different in Europe and Australia, where myxomatosis and rabbit hemorrhagic disease are endemic. Advances in epidemiology and virology have led to detection of other lapine viruses that are now recognized as agents of emerging infectious diseases. Rabbit caliciviruses, related to rabbit hemorrhagic disease, are generally avirulent, but lethal variants are being identified in Europe and North America. Enteric viruses including lapine rotavirus, rabbit enteric coronavirus and rabbit astrovirus are being acknowledged as contributors to the multifactorial enteritis complex of juvenile rabbits. Three avirulent leporid herpesviruses are found in domestic rabbits. A fourth highly pathogenic virus designated leporid herpesvirus 4 has been described in Canada and Alaska. This review considers viruses affecting rabbits by their clinical significance. Viruses of major and minor clinical significance are described, and viruses of laboratory significance are mentioned. Copyright © 2013 Elsevier Inc. All rights reserved.

  8. Indocyanine green enables near-infrared fluorescence imaging of lipid-rich, inflamed atherosclerotic plaques.

    PubMed

    Vinegoni, Claudio; Botnaru, Ion; Aikawa, Elena; Calfon, Marcella A; Iwamoto, Yoshiko; Folco, Eduardo J; Ntziachristos, Vasilis; Weissleder, Ralph; Libby, Peter; Jaffer, Farouc A

    2011-05-25

    New high-resolution molecular and structural imaging strategies are needed to visualize high-risk plaques that are likely to cause acute myocardial infarction, because current diagnostic methods do not reliably identify at-risk subjects. Although molecular imaging agents are available for low-resolution detection of atherosclerosis in large arteries, a lack of imaging agents coupled to high-resolution modalities has limited molecular imaging of atherosclerosis in the smaller coronary arteries. Here, we have demonstrated that indocyanine green (ICG), a Food and Drug Administration-approved near-infrared fluorescence (NIRF)-emitting compound, targets atheromas within 20 min of injection and provides sufficient signal enhancement for in vivo detection of lipid-rich, inflamed, coronary-sized plaques in atherosclerotic rabbits. In vivo NIRF sensing was achieved with an intravascular wire in the aorta, a vessel of comparable caliber to human coronary arteries. Ex vivo fluorescence reflectance imaging showed high plaque target-to-background ratios in atheroma-bearing rabbits injected with ICG compared to atheroma-bearing rabbits injected with saline. In vitro studies using human macrophages established that ICG preferentially targets lipid-loaded macrophages. In an early clinical study of human atheroma specimens from four patients, we found that ICG colocalized with plaque macrophages and lipids. The atheroma-targeting capability of ICG has the potential to accelerate the clinical development of NIRF molecular imaging of high-risk plaques in humans.

  9. Converging Stereotactic Radiotherapy Using Kilovoltage X-Rays: Experimental Irradiation of Normal Rabbit Lung and Dose-Volume Analysis With Monte Carlo Simulation

    SciTech Connect

    Kawase, Takatsugu; Kunieda, Etsuo Deloar, Hossain M.; Tsunoo, Takanori; Seki, Satoshi; Oku, Yohei; Saitoh, Hidetoshi; Saito, Kimiaki; Ogawa, Eileen N.; Ishizaka, Akitoshi; Kameyama, Kaori; Kubo, Atsushi

    2009-10-01

    Purpose: To validate the feasibility of developing a radiotherapy unit with kilovoltage X-rays through actual irradiation of live rabbit lungs, and to explore the practical issues anticipated in future clinical application to humans through Monte Carlo dose simulation. Methods and Materials: A converging stereotactic irradiation unit was developed, consisting of a modified diagnostic computed tomography (CT) scanner. A tiny cylindrical volume in 13 normal rabbit lungs was individually irradiated with single fractional absorbed doses of 15, 30, 45, and 60 Gy. Observational CT scanning of the whole lung was performed every 2 weeks for 30 weeks after irradiation. After 30 weeks, histopathologic specimens of the lungs were examined. Dose distribution was simulated using the Monte Carlo method, and dose-volume histograms were calculated according to the data. A trial estimation of the effect of respiratory movement on dose distribution was made. Results: A localized hypodense change and subsequent reticular opacity around the planning target volume (PTV) were observed in CT images of rabbit lungs. Dose-volume histograms of the PTVs and organs at risk showed a focused dose distribution to the target and sufficient dose lowering in the organs at risk. Our estimate of the dose distribution, taking respiratory movement into account, revealed dose reduction in the PTV. Conclusions: A converging stereotactic irradiation unit using kilovoltage X-rays was able to generate a focused radiobiologic reaction in rabbit lungs. Dose-volume histogram analysis and estimated sagittal dose distribution, considering respiratory movement, clarified the characteristics of the irradiation received from this type of unit.

  10. Antihypercholesterolemic and antioxidant efficacies of zerumbone on the formation, development, and establishment of atherosclerosis in cholesterol-fed rabbits

    PubMed Central

    Hemn, Hassan Othman; Noordin, Muhammad Mustapha; Rahman, Heshu Sulaiman; Hazilawati, Hamza; Zuki, Abubakr; Chartrand, Max Stanley

    2015-01-01

    Owing to the high incidence of cholesterol-induced cardiovascular disease, particularly atherosclerosis, the current study was designed to investigate the preventive and therapeutic efficacies of dietary zerumbone (ZER) supplementation on the formation and development of atherosclerosis in rabbits fed with a high cholesterol diet. A total of 72 New Zealand white rabbits were divided randomly on two experimental studies carried out 8 weeks apart. The first experiment was designed to investigate the prophylactic efficacy of ZER in preventing early developed atheromatous lesion. The second experimental trial was aimed at investigating the therapeutic effect of ZER in reducing the atherosclerotic lesion progression and establishment. Sudanophilia, histopathological, and ultrastructural changes showed pronounced reduction in the plaque size in ZER-medicated aortas. On the other hand, dietary supplementation of ZER for almost 10 weeks as a prophylactic measure indicated substantially decreasing lipid profile values, and similarly, plaque size in comparison with high-cholesterol non-supplemented rabbits. Furthermore, the results of oxidative stress and antioxidant biomarker evaluation indicated that ZER is a potent antioxidant in suppressing the generation of free radicals in terms of atherosclerosis prevention and treatment. ZER significantly reduced the value of malondialdehyde and augmented the value of superoxide dismutase. In conclusion, our data indicated that dietary supplementation of ZER at doses of 8, 16, and 20 mg/kg alone as a prophylactic measure, and as a supplementary treatment with simvastatin, significantly reduced early plague formation, development, and establishment via significant reduction in serum lipid profile, together with suppression of oxidative damage, and therefore alleviated atherosclerosis lesions. PMID:26347047

  11. Does myxomatosis still regulate numbers of rabbits (Oryctolagus cuniculus Linnaeus, 1758) in the United Kingdom?

    PubMed

    Trout, R C; Ross, J; Fox, A P

    1993-03-01

    Myxomatosis now kills a much smaller proportion of rabbit populations than in the past, while remaining an important regulatory factor, as shown experimentally. On two separate occasions, experimental reduction of the prevalence of the disease (by reducing infestations of the main vector, the rabbit flea) led to significant increases in numbers of rabbits surviving the winter.

  12. Does artificial ascites induce the heat-sink phenomenon during percutaneous radiofrequency ablation of the hepatic subcapsular area?: an in vivo experimental study using a rabbit model.

    PubMed

    Kim, Young Sun; Rhim, Hyunchul; Choi, Dongil; Lim, Hyo K

    2009-01-01

    To evaluate the effect of the heat-sink phenomenon induced by artificial ascites on the size of the ablation zone during percutaneous radiofrequency (RF) ablation of the hepatic subcapsular area in an in vivo rabbit model. A total of 21 percutaneous rabbit liver RF ablations were performed with and without artificial ascites (5% dextrose aqueous solution). The rabbits were divided into three groups: a) control group (C, n = 7); b) room temperature ascites group (R, n = 7); and c) warmed ascites group (W, n = 7). The tip of a 1 cm, internally cooled electrode was placed on the subcapsular region of the hepatic dome via ultrasound guidance, and ablation was continued for 6 min. Changes in temperature of the ascites were monitored during the ablation. The size of the ablation zones of the excised livers and immediate complications rates were compared statistically between the groups (Mann-Whitney U test, Kruskal-Wallis test, linear-by-linear association, p = 0.05). One rabbit from the "W" group expired during the procedure. In all groups, the ascites temperatures approached their respective body temperatures as the ablations continued; however, a significant difference in ascites temperature was found between groups "W" and "R" throughout the procedures (39.2+/-0.4 degrees C in group W and 33.4+/-4.3 degrees C in group R at 6 min, p = 0.003). No significant difference was found between the size of the ablation zones (782.4+/-237.3 mL in group C, 1,172.0+/-468.9 mL in group R, and 1,030.6+/-665.1 mL in group W, p = 0.170) for the excised liver specimens. Diaphragmatic injury was identified in three of seven cases (42.9%) upon visual inspection of group "C" rabbits (p = 0.030). Artificial ascites are not likely to cause a significant heat-sink phenomenon in the percutaneous RF ablation of the hepatic subcapsular region.

  13. Macrophage heterogeneity in atherosclerotic plaques.

    PubMed

    Johnson, Jason L; Newby, Andrew C

    2009-10-01

    The varied behaviour of macrophages and foam cells during atherosclerosis and its clinical sequelae prompt the question whether all these activities can be the property of a single cell population. Subsets of monocytes with distinct patterns of surface markers and behaviours during inflammation have recently been characterized and shown to have complementary roles during progression of atherosclerosis. A variety of macrophage phenotypes derived from these monocyte subsets in response to mediators of innate and acquired immunity have also been found in plaques. Based on functional properties and genomic signatures, they may have different impacts on facets of plaque development, including fibrous cap and lipid core formation. Monocyte and macrophage phenotypic diversity is important in atherogenesis. More work is needed to define consistent marker sets for the different foam cell phenotypes in experimental animals and humans. Cell tracking studies are needed to establish their relationship with monocyte subtypes. In addition, genetic and pharmacological manipulation of phenotypes will be useful to define their functions and exploit the resulting therapeutic potential.

  14. Experimental bacterial pneumonia in rabbits: polymorphonuclear leukocyte margination and sequestration in rabbit lungs and quantitation and kinetics of /sup 51/Cr-labeled polymorphonuclear leukocytes in E. coli-induced lung lesions

    SciTech Connect

    Cybulsky, M.I.; Movat, H.Z.

    1982-12-01

    A relationship between the circulating and marginal polymorphonuclear leukocyte (PMN) pools was documented using /sup 51/Cr-labeled leukocytes as a marker. /sup 51/Cr-leukocytes marginating in the lungs were found to decrease following a first-order exponential decline, while /sup 51/Cr radioactivity accumulated in the liver and the spleen. Intravenously administered endotoxin caused a rapid selective disappearance of PMNs from the circulation. The percentage of infused /sup 51/Cr cells disappearing was equal to the percentage of disappearance of host cells. The PMNs were found to sequester in the lungs, with peak sequestration of labeled cells occurring 5 min after an endotoxin challenge. Over the next 25 min the /sup 51/Cr radioactivity in the lungs declined. Large numbers of PMNs, probably newly derived from the bone marrow, were observed histologically to be sequestered in the lung vasculature 90 min after an endotoxin dose, while the early sequestration of circulating leukocytes could not be assessed histologically. Pulmonary inflammatory lesions were induced selectively with Escherichia coli in the left lower lobes of rabbits, leaving the right lower lobes as intrinsic controls. PMN-accumulation into the lesions was quantitated using /sup 51/Cr-labeled blood leukocytes. With the aid of /sup 125/I-labeled E. coli, a logarithmic dose-response relationship was found between the number of E. coli and of PMNs. Over a 6-hr period circulating PMNs were found to accumulate in a lesion in the left lower lobe, whereas in the control right lower lobe, leukocyte radioactivity declined. These findings were confirmed with the aid of lavages of the right and left lungs. Two peaks of PMN-accumulation were found by studying leukocyte kinetics: a larger peak between 0 and 6 hr and a smaller peak 18-24 hr after instillation of the microorganisms. Histologic studies confirmed the accumulation of leukocytes, and by 3 weeks showed a complete resolution of the lesions.

  15. Tendon Tissue Engineering and Its Role on Healing of the Experimentally Induced Large Tendon Defect Model in Rabbits: A Comprehensive In Vivo Study

    PubMed Central

    Meimandi-Parizi, Abdolhamid; Oryan, Ahmad; Moshiri, Ali

    2013-01-01

    Healing of large tendon defects is challenging. We studied the role of collagen implant with or without polydioxanone (PDS) sheath on the healing of a large Achilles tendon defect model, in rabbits. Sixty rabbits were divided into three groups. A 2 cm gap was created in the left Achilles tendon of all rabbits. In the control lesions, no implant was used. The other two groups were reconstructed by collagen and collagen-PDS implants respectively. The animals were clinically examined at weekly intervals and their lesions were observed by ultrasonography. Blood samples were obtained from the animals and were assessed for hematological analysis and determination of serum PDGF level, at 60 days post injury (DPI). The animals were then euthanized and their lesions were assessed for gross and histopathology, scanning electron microscopy, biomechanical testing, dry matter and hydroxyproline content. Another 65 pilot animals were also studied grossly and histopathologically to define the host implant interaction and graft incorporation at serial time points. The treated animals gained significantly better clinical scoring compared to the controls. Treatment with collagen and collagen-PDS implants significantly increased the biomechanical properties of the lesions compared to the control tendons at 60DPI (P<0.05). The tissue engineered implants also reduced peritendinous adhesion, muscle fibrosis and atrophy, and increased ultrasonographical echogenicity and homogenicity, maturation and differentiation of the collagen fibrils and fibers, tissue alignment and volume of the regenerated tissue compared to those of the control lesions (P<0.05). The implants were gradually absorbed and substituted by the new tendon. Implantation of the bioimplants had a significant role in initiating tendon healing and the implants were biocompatible, biodegradable and safe for application in tendon reconstructive surgery. The results of the present study may be valuable in clinical practice. PMID

  16. Experimental evaluation of myocardial fibrosis in a rapid atrial pacing model in New Zealand rabbits using quantitative analysis of ultrasonic backscatter.

    PubMed

    Sun, Juan; Rong, Zhang; Wugeti, Najina; Azhati, Adila; GUo, Yujun; Liu, Haili; Qian, Ruping; Zhao, Long; Ma, Yitong

    2014-10-09

    The aim of this study was the establishment of a rapid atrial pacing (RAP)-induced atrial fibrillation (AF) model with electrophotoluminescence and the application of ultrasonic backscatter quantitative analysis of the degree of myocardial fibrosis in New Zealand white rabbits. Sixteen New Zealand white rabbits were randomly divided into 2 groups: 1) a sham operation group (n=8) with implanted electrodes and no rapid pacing and 2) a pacing group (n=8) with an AF model induced by short-term rapid right atrial pacing for 12 h. Establishment of an AF model, atrial myocardium of myocardial fibrosis was tested by Masson staining and expression of collagen I and collagen III protein was detected with pathologic immunohistochemistry integrated back-scatter (IBS). Back scattering integral cycle variation (CVIB) were detected in atrial septal and posterior wall of the right atrium. Rapid atrial pacing successfully induced the atrial fibrillation model in rabbits. Masson staining showed myocardial fibrosis significantly increased in the pacing group. Expression of collagen I and collagen III protein was strongly positive in the pacing group, and expression of collagen I and collagen III protein were weakly positive in the sham operation group. Compared with the sham operation group, AII was increased (8.24±0.85 vs. 15.56±1.30, P<0.05) and (7.58±0.56 vs. 16.60±2.45, P<0.05). CVIB was significantly decreased (2.78±0.86 vs. 1.08±0.13, P<0.05) and (3.12±0.65 vs. 1.56±0.15, P<0.05) in septal and posterior wall of the right atrium of the pacing group. Ultrasonic backscatter measurement technique can be used to evaluate degree of myocardial fibrosis in a right atrial pacing-induced atrial arrhythmia model.

  17. The effect of bone growth factor in the tendon to bone healing in anterior cruciate ligament reconstruction: An experimental study in rabbits

    PubMed Central

    Al-Bluwi, Mohammed T; Azam, Md Q; Sadat-Ali, Mir

    2016-01-01

    Background: Reconstruction of the anterior cruciate ligament (ACL) involves use of semintendinosis and gracilis tendons graft that is transplanted into bone tunnels at the femoral and tibial insertion sites and the sites and the bone tendon interface is a weak link in the early healing period due to slow rate of healing. We hypothesized that an addition of bone growth factor like Sadat-Habdan mesenchymal stimulating peptide (SHMSP) could enhance bone tendon healing rate so that re-rupture of the tendon does not take place. Methodology: Twenty skeletally mature rabbits underwent ACL reconstruction of the right knee. In 10 of the rabbits at the site of the tendon-graft 5 mg/kg body weight of SHMSP was put in the bone tunnel. In 10 other animals, nothing was added. At eight and 12 weeks 5 animals from each group were sacrificed. The tendon-graft site was harvested and sent for histopathological examination to assess the healing at the tendon-bone graft to the tibial tunnel. Results: There were no deaths in both the groups. One rabbit of the control group developed an infection. In all the animals of the study group from 4 weeks onward showed bone formation, wherein the control group only granulation tissue was observed. By 8 weeks in the study group, the canal was totally obliterated with the new bone formation which extended onto the periosteal area. In the control, there was minimal change in the formation of the new bone formation. Conclusion: Addition of a growth factor like SHMSP would enhance the osteo-integration of the tendon-graft in the bony tunnel after ACL reconstruction in vivo. PMID:26958518

  18. Effect of low-level laser therapy irradiation and Bio-Oss graft material on the osteogenesis process in rabbit calvarium defects: a double blind experimental study.

    PubMed

    Rasouli Ghahroudi, Amir Alireza; Rokn, Amir Reza; Kalhori, Katayoun A M; Khorsand, Afshin; Pournabi, Alireza; Pinheiro, A L B; Fekrazad, Reza

    2014-05-01

    This study aims to assess the effect of low-level laser therapy (LLLT) irradiation and Bio-Oss graft material on the osteogenesis process in the rabbit calvarium defects. Twelve white male New Zealand rabbits were included in this study. Four 8-mm diameter identical defects were prepared on each rabbit's calvarium. One site was left as an untreated control (C), the second site was filled with Bio-Oss (B), the third site was treated with laser irradiation (L), and the fourth site treated with Bio-Oss and laser irradiation (B + L). In the laser group, a diode laser (wavelength 810 nm, output power 300 mW, irradiation mode CW, energy density 4 J/cm2) was applied immediately after surgery and then one other day for the next 20 days. After 4 and 8 weeks, the animals were sacrificed and histological and histomorphometric examinations were performed and the data were subjected to Friedman and repeated measurements ANOVA tests. Significant differences were not found regarding inflammation severity, foreign body reactions, and vitality of newly formed bone on 4th and 8th week after operation. The mean amount of new bone was 15.83 and 18.5% in the controls on the 4th and 8th week; 27.66 and 25.16% in the laser-irradiated group; 35.0 and 41.83% in Bio-Oss and 41.83 and 47.0% in the laser + Bio-Oss treated specimens with significant statistical differences (p <0.05). Application of LLLT in combination with Bio-Oss® can promote bone healing. Therefore, LLLT may be clinically beneficial in promoting bone formation in skeletal defects.

  19. Simulation of human atherosclerotic femoral plaque tissue: the influence of plaque material model on numerical results

    PubMed Central

    2015-01-01

    Background Due to the limited number of experimental studies that mechanically characterise human atherosclerotic plaque tissue from the femoral arteries, a recent trend has emerged in current literature whereby one set of material data based on aortic plaque tissue is employed to numerically represent diseased femoral artery tissue. This study aims to generate novel vessel-appropriate material models for femoral plaque tissue and assess the influence of using material models based on experimental data generated from aortic plaque testing to represent diseased femoral arterial tissue. Methods Novel material models based on experimental data generated from testing of atherosclerotic femoral artery tissue are developed and a computational analysis of the revascularisation of a quarter model idealised diseased femoral artery from a 90% diameter stenosis to a 10% diameter stenosis is performed using these novel material models. The simulation is also performed using material models based on experimental data obtained from aortic plaque testing in order to examine the effect of employing vessel appropriate material models versus those currently employed in literature to represent femoral plaque tissue. Results Simulations that employ material models based on atherosclerotic aortic tissue exhibit much higher maximum principal stresses within the plaque than simulations that employ material models based on atherosclerotic femoral tissue. Specifically, employing a material model based on calcified aortic tissue, instead of one based on heavily calcified femoral tissue, to represent diseased femoral arterial vessels results in a 487 fold increase in maximum principal stress within the plaque at a depth of 0.8 mm from the lumen. Conclusions Large differences are induced on numerical results as a consequence of employing material models based on aortic plaque, in place of material models based on femoral plaque, to represent a diseased femoral vessel. Due to these large

  20. Delivery of antifibroblast agents as adjuncts to filtration surgery. Part I--Periocular clearance of cobalt-57 bleomycin in experimental drug delivery: pilot study in the rabbit

    SciTech Connect

    Kay, J.S.; Litin, B.S.; Woolfenden, J.M.; Chvapil, M.; Herschler, J.

    1986-10-01

    Antitumor and antifibroblast agents show promise as adjuncts after glaucoma filtration surgery in reducing postoperative scarring and failure. We used nuclear imaging in rabbits to investigate periocular clearance of one such agent (/sup 57/Co-bleomycin). Sub-Tenon injection was compared to other delivery techniques. Our results showed that a collagen sponge and a silastic disc implant with a microhole prolonged drug delivery when compared to sub-Tenon injection alone or injection with a viscosity enhancing agent (0.5% sodium hyaluronate). We theorize that if an antifibroblast agent can be delivered in small and sustained amounts after filtration surgery, this may prolong bleb longevity and avoid unnecessary drug toxicity.

  1. Is limited prehospital resuscitation with plasma more beneficial than using a synthetic colloid? An experimental study in rabbits with parenchymal bleeding.

    PubMed

    Kheirabadi, Bijan S; Valdez-Delgado, Krystal K; Terrazas, Irasema B; Miranda, Nahir; Dubick, Michael A

    2015-04-01

    Reports of survival benefits of early transfusion of plasma with red blood cells (1:1 ratio) in trauma patients suggest that plasma may be a better fluid to replace Hextend for battlefield resuscitation. We studied possible advantages of prehospital resuscitation with plasma compared with Hextend or albumin in a model of uncontrolled hemorrhage. Male New Zealand white rabbits (3.3 ± 0.1 kg) were anesthetized, instrumented, and subjected to a splenic injury with uncontrolled bleeding. Ten minutes after injury (mean arterial pressure [MAP] < 40 mm Hg), the rabbits received small and equal volumes (15 mL/kg) of rabbit plasma (n = 10), Hextend (n = 10), or 5% human albumin (n = 9) or no fluid. Fluids were administered in two bolus injections (20 minutes apart) and targeted to a MAP of 65 mm Hg. Animals were monitored for 2.5 hours or until death, and their blood losses were measured. Arterial blood samples were collected at different times and analyzed for ABG, CBC, and coagulation tests. There were no differences in baseline measures among groups. Splenic injury caused similar hemorrhages (9.1 ± 0.4 mL/kg at 10 minutes) and decreased MAP in all subjects. Subsequent resuscitation initiated additional bleeding. At 60 minutes after injury (20 minutes after resuscitation), longer activated partial thromboplastin time and lower fibrinogen concentrations were apparent compared with baseline values with differences among groups. Thrombelastography analysis indicated faster and stronger clot formation with plasma and albumin resuscitation than with Hextend use. Shock indices were increased in all groups, but smaller changes were measured in the albumin group. Total blood loss did not differ among resuscitated rabbits but was higher (p < 0.05) than among nonresuscitated animals. Survival rates were 11% (untreated), 40% (Hextend and plasma), and 89% (albumin, p < 0.05). Resuscitation with plasma or albumin better preserved coagulation function than did Hextend. However

  2. Local Administration of NF-{kappa} B Decoy Oligonucleotides to Prevent Restenosis after Balloon Angioplasty: An Experimental Study in New Zealand White Rabbits

    SciTech Connect

    Kalinowski, Marc Viehofer, Kerstin; Hamann, Christine; Barry, James J.; Kleb, Beate; Klose, Klaus Jochen; Wagner, Hans-Joachim; Alfke, Heiko

    2005-04-15

    Purpose. To evaluate the efficacy of NF-{kappa} B oligonucleotides (ODN) administered by local administration with the channeled balloon catheter to prevent restenosis after balloon angioplasty in restenotic iliac arteries of New Zealand white rabbits. Materials and Methods. In vitro, 8000 rabbit vascular smooth muscle cells (rVSMC) where transfected with a liposomal carrier (TfX50) with 100 ng of decoy and scrambled ODN. Inhibition of proliferation was measured using a MTT assay after 24 hours in comparison to control. In vivo, 22 male New Zealand White rabbits were fed a 1% cholesterol diet and received denudation of both common iliac arteries with a 3 mm balloon catheter to induce an arterial stenosis. Four weeks after stenosis induction, local application of NF-{kappa} B in two different concentrations (1 {mu}g: n = 14; 10 {mu}g: n = 8) was performed randomly on one common iliac artery. Scrambled oligonucleotides without specific binding capacities were injected into the contralateral side. The channeled balloon catheter allows simultaneous balloon dilation (8 atm) of the stenosis and local application of a drug solution (2 atm). Four weeks after local drug delivery the animals were killed and the vessels were excised and computerized morphometric measurements were performed. Results. NF-{kappa} B decoy ODN but not scrambled ODN inhibited proliferation of rVSMC in vitro. Following local ODN application in the animals, no acute vascular complications were seen. NF-{kappa} B ODN resulted in a statistically non significant reduction of neointimal area compared to the control group. The neointimal area was 0.97 mm{sup 2} using 1 {mu}g NF-{kappa} B ODN compared to 0.98 mm{sup 2} in the control group. The higher dose resulted in a neointimal area of 0.97 mm{sup 2} compared to 1.07mm{sup 2} at the control side. Conclusions. Local drug delivery of NF-{kappa} B ODN using the 'channeled balloon' catheter could not reduce neointimal hyperplasia in stenostic rabbit iliac

  3. Influence of type of medullary nail on the development of local infection. An experimental study of solid and slotted nails in rabbits.

    PubMed

    Melcher, G A; Claudi, B; Schlegel, U; Perren, S M; Printzen, G; Munzinger, J

    1994-11-01

    Any operation involving the implantation of a foreign body increases the risk of infection. The implant material and its surface, the dead space, and any necrosis or vascular changes play a significant role in susceptibility to infection. We investigated the effect of the dead space in an intramedullary nail on the rate of local infection. We inoculated the intramedullary cavities of rabbit tibiae with various concentrations of a human pathogen, of Staphylococcus aureus strain, and then inserted either a solid or a hollow slotted stainless-steel nail. We found a significantly higher rate of infection after use of the slotted nail (59%) than after the solid nail (27%) (p < 0.05).

  4. Experimental embolization of rabbit renal arteries to compare the effects of poly L-lactic acid microspheres with and without epirubicin release against ntraarterial injection of epirubicin

    SciTech Connect

    Fujiwara, Kazuhisa; Hayakawa, Katsumi; Nagata, Yasushi; Hiraoka, Masahiro; Nakamura, Tatsuo; Shimizu, Yoshihiko; Ikada, Yoshito

    2000-05-15

    Purpose: We performed a basic investigation using white rabbits of the sustained release and embolizing effects of poly L-lactic acid microspheres (PLA) to determine their usefulness for chemoembolization.Methods: Fifteen male Japanese white rabbits were used. Sustained release of an embolizing material, EPI-PLA was accomplished with l m g of PLA containing 0.03 mg of epirubicin hydrochloride (EPI). Embolization with 50 mg of PLA (total dose of EPI l.5 mg) was performed after the renal artery of the rabbits was selected (Chemo-TAE group). A group in which a bolus of 1.5 mg EPI alone was injected through the renal artery (TAI group) was established as a control group. Furthermore, a group in which embolization was performed with 50 mg of PLA alone (TAE group) was also established. These three groups, each consisting of five rabbits, were compared.Results: Blood EPI levels were serially measured. The blood EPI level in the TAI group rapidly reached a peak more than 30 min after injection, then decreased to almost zero 24 hr after injection. In the Chemo-TAE group, the blood EPI level was transiently increased 30 min after embolization, but remained low thereafter until 24 hr after embolization. EPI levels in kidney tissue isolated 24 hr after embolization were measured. In the Chemo-TAE group, the tissue EPI level was significantly higher than that in the TAI group. When isolated kidneys were macroscopically and histologically examined, atrophy of the entire embolized kidney, as well as infarction and necrosis in the renal cortex, were observed in both the TAE group and the Chemo-TAE group. However, there were no such findings in the TAI group. The area of the infarction in the renal cortex did not significantly differ between the Chemo-TAE group and the TAE group; however, there was vascular injury in the Chemo-TAE group and none in the TAE group.Conclusion: It was demonstrated that EPI-PLA, a chemo-embolizing material, maintained high local concentrations of the

  5. Experimental Embolization of Rabbit Renal Arteries to Compare the Effects of Poly L-Lactic Acid Microspheres With and Without Epirubicin Release Against Intraarterial Injection of Epirubicin

    SciTech Connect

    Fujiwara, Kazuhisa; Hayakawa, Katsumi; Nagata, Yasushi; Hiraoka, Masahiro; Nakamura, Tatsuo; Shimizu, Yoshihiko; Ikada, Yoshito

    2000-03-15

    Purpose: We performed a basic investigation using white rabbits of the sustained release and embolizing effects of poly L-lactic acid microspheres (PLA) to determine their usefulness for chemoembolization.Methods: Fifteen male Japanese white rabbits were used. Sustained release of an embolizing material, EPI-PLA was accomplished with 1 mg of PLA containing 0.03 mg of epirubicin hydrochloride (EPI). Embolization with 50 mg of PLA (total dose of EPI 1.5 mg) was performed after the renal artery of the rabbits was selected (Chemo-TAE group). A group in which a bolus of 1.5 mg EPI alone was injected through the renal artery (TAI group) was established as a control group. Furthermore, a group in which embolization was performed with 50 mg of PLA alone (TAE group) was also established. These three groups, each consisting of five rabbits, were compared.Results: Blood EPI levels were serially measured. The blood EPI level in the TAI group rapidly reached a peak more than 30 min after injection, then decreased to almost zero 24 hr after injection. In the Chemo-TAE group, the blood EPI level was transiently increased 30 min after embolization, but remained low thereafter until 24 hr after embolization. EPI levels in kidney tissue isolated 24 hr after embolization were measured. In the Chemo-TAE group, the tissue EPI level was significantly higher than that in the TAI group. When isolated kidneys were macroscopically and histologically examined, atrophy of the entire embolized kidney, as well as infarction and necrosis in the renal cortex, were observed in both the TAE group and the Chemo-TAE group. However, there were no such findings in the TAI group. The area of the infarction in the renal cortex did not significantly differ between the Chemo-TAE group and the TAE group; however, there was vascular injury in the Chemo-TAE group and none in the TAE group.Conclusion: It was demonstrated that EPI-PLA, a chemoembolizing material, maintained high local concentrations of the

  6. The influence of intravenous laser irradiation of blood on some metabolic and functional parameters in intact rabbits and experimental cerebral ischaemia

    NASA Astrophysics Data System (ADS)

    Nechipurenko, N.; Vasilevskaya, L.; Musienko, J.; Maslova, G.

    2007-07-01

    It has been studied the intravenous laser irradiation of blood (ILIB) influence with helium-neon laser (HNL) of 630 nm wavelength on some of lipid peroxidation (LPO) and antioxidant system (AOS) findings, aside-base status (ABS) and blood oxygen transport (BOT), state of dermal microhaemodynamics (MGD) in the intact rabbits and after modeling of local ischemia of brain (LIB). Depending on conditions of organism functioning (norm or brain ischaemia) ILIB has resulted in stimulating or normalizing effects on the whole metabolic and microhaemocirculation processes which had been studied during our investigation. It is discussed the mechanisms of pathogenetic directivity of ILIB influence in cerebral ischaemia

  7. Atherosclerotic Plaque Targeting Mechanism of Long-Circulating Nanoparticles Established by Multimodal Imaging

    PubMed Central

    Lobatto, Mark E.; Calcagno, Claudia; Millon, Antoine; Senders, Max L.; Fay, Francois; Robson, Philip M.; Ramachandran, Sarayu; Binderup, Tina; Paridaans, Maarten P.M.; Sensarn, Steven; Rogalla, Stephan; Gordon, Ronald E.; Cardoso, Luis; Storm, Gert; Metselaar, Josbert M.; Contag, Christopher H.; Stroes, Erik S. G.; Fayad, Zahi A.; Mulder, Willem J.M.

    2015-01-01

    Atherosclerosis is a major cause of global morbidity and mortality that could benefit from novel targeted therapeutics. Recent studies have shown efficient and local drug delivery with nanoparticles, although the nanoparticle targeting mechanism for atherosclerosis has not yet been fully elucidated. Here we used in vivo and ex vivo multimodal imaging to examine permeability of the vessel wall and atherosclerotic plaque accumulation of fluorescently labeled liposomal nanoparticles in a rabbit model. We found a strong correlation between permeability as established by in vivo dynamic contrast enhanced magnetic resonance imaging and nanoparticle plaque accumulation with subsequent nanoparticle distribution throughout the vessel wall. These key observations will enable the development of nanotherapeutic strategies for atherosclerosis. PMID:25619964

  8. Immunoelectron-microscopic localization of S-protein/vitronectin in human atherosclerotic wall.

    PubMed

    Niculescu, F; Rus, H G; Poruţiu, D; Ghiurca, V; Vlaicu, R

    1989-08-01

    S-protein/vitronectin is a multifunctional glycoprotein interacting with both complement activation and coagulation pathways. Its presence was investigated in 5 femoral and 5 iliac atherosclerotic human arteries, obtained at surgery, by immunoelectron microscopy using an affinity purified rabbit IgG specific for human S-protein/vitronectin. The immunoelectron dense specific deposits were found in both intimal thickenings and fibrous plaques in association with elastic fibers, collagen bundles and cell debris in the vicinity of elastin. Cell debris embedded in the collagen matrix were S-protein/vitronectin negative. S-protein/vitronectin was also absent on intact cells, lipid droplets and cholesterol clefts. All cell debris, however, was positive for C5b-9 deposits suggesting that complement activation had occurred at these sites with or without S-protein/vitronectin interaction. S-protein/vitronectin may play a role in the arterial wall defence by restricting the extent of complement activation.

  9. Cells carrying C5b-9 complement complexes in human atherosclerotic wall.

    PubMed

    Rus, H G; Niculescu, F; Poruţiu, D; Ghiurca, V; Vlaicu, R

    1989-03-01

    Fibrous plaques and intimal thickenings of 5 femoral and 5 iliac human arteries obtained at surgery were processed for indirect and double-labeling immunoelectron microscopy using an affinity purified rabbit IgG anti-C5b-9 neoantigen and the EBM 11 monoclonal antibody anti-human macrophages. The C5b-9 complexes were localized in intact cells, disintegrated cells and cell debris enmeshed in the connective tissue matrix. Some of the cell debris bearing C5b-9 deposits was found to be of macrophage origin. Endocyted or exocyted pieces of membrane with pore-forming C5b-9 complexes were also identified. Damage of cells by complement in atherosclerotic lesions may contribute to atherogenesis.

  10. On the photobleaching of native and exogenous (BPD-MA) fluorescence: Quantification of kinetics and its role in diagnostics in tumor and atherosclerotic animal models

    NASA Astrophysics Data System (ADS)

    Papaioannou, Thanassis

    Fluorescence photobleaching (Phbl) is a process via which molecules, gradually loose their ability to fluoresce. It is present, to a lesser or greater degree, in all fluorescent-based biomedical techniques and thus plays an important role in their reliability and implementation. The purpose of this work was to quantify the dynamics of fluorescence PhBl in two animal models and investigate its role in pertinent fluorescence diagnostics. To this end, we have used a tumor bearing rat model (Prostatic Adenocarcinoma, PA-III) and an atherosclerotic rabbit model. The former model was used to (a) quantify the PhBl dynamics of native and exogenous (BPD-MA) fluorescence, and (b) to examine the relationship of this dynamics with the histopathology. The native and exogenous fluorescence spectrum of four animal sites (primary tumor, mesenteric-I, right and left iliac lymph nodes) were simultaneously monitored during continuous laser irradiation (442 nm). PhBl dynamics were described by biexponential decays. The values of the fast/slow decay parameters differed by approximately an order of magnitude for both the native (˜1 sec/˜10 sec) and BPD-MA fluorescence (˜1.5 sec/˜15 sec). Strong correlation between the PhBl dynamics and histopathology allowed for discrimination between metastatic and normal or inflammatory lymph nodes. The atherosclerotic model was used to (a) quantify the PhBl of native fluorescence of normal and atherosclerotic rabbit arterial wall, and (b) to investigate its influence on the spectro-temporal parameters used for diagnosis of atherosclerotic lesions. PhBl was also characterized by second order kinetics and was influenced by both fluence and fluence rate. Within the range of fluences used in this study, the time-dependent characteristics of rabbit arterial fluorescence were unaffected by PhBl. Acceptable excitation levels for optimal tissue interrogation were established.

  11. Treatment of patients with aortic atherosclerotic disease with paclitaxel-associated lipid nanoparticles

    PubMed Central

    Shiozaki, Afonso A.; Senra, Tiago; Morikawa, Aleksandra T.; Deus, Débora F.; Paladino, Antonio T; Pinto, Ibraim M.F.; Maranhão, Raul C.

    2016-01-01

    OBJECTIVE: The toxicity of anti-cancer chemotherapeutic agents can be reduced by associating these compounds, such as the anti-proliferative agent paclitaxel, with a cholesterol-rich nanoemulsion (LDE) that mimics the lipid composition of low-density lipoprotein (LDL). When injected into circulation, the LDE concentrates the carried drugs in neoplastic tissues and atherosclerotic lesions. In rabbits, atherosclerotic lesion size was reduced by 65% following LDE-paclitaxel treatment. The current study aimed to test the effectiveness of LDE-paclitaxel on inpatients with aortic atherosclerosis. METHODS: This study tested a 175 mg/m2 body surface area dose of LDE-paclitaxel (intravenous administration, 3/3 weeks for 6 cycles) in patients with aortic atherosclerosis who were aged between 69 and 86 yrs. A control group of 9 untreated patients with aortic atherosclerosis (72-83 yrs) was also observed. RESULTS: The LDE-paclitaxel treatment elicited no important clinical or laboratory toxicities. Images were acquired via multiple detector computer tomography angiography (64-slice scanner) before treatment and at 1-2 months after treatment. The images showed that the mean plaque volume in the aortic artery wall was reduced in 4 of the 8 patients, while in 3 patients it remained unchanged and in one patient it increased. In the control group, images were acquired twice with an interval of 6-8 months. None of the patients in this group exhibited a reduction in plaque volume; in contrast, the plaque volume increased in three patients and remained stable in four patients. During t