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Sample records for experimental rabbit atherosclerotic

  1. 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.

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. 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

  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. 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.

  4. 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.

  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. 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.

  7. [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

  8. 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

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. Effect of Fenugreek Seeds Powder (Trigonella foenum-graecum L.) on Experimental Induced Hyperlipidemia in Rabbits.

    PubMed

    Sharma, Megh Shyam; Choudhary, Prema Ram

    2016-04-12

    In the present experimental study, the effect of Trigonella foenum-graecum L. (TFG) seeds powder on experimentally induced hyperlipidemia in rabbits was investigated. Twenty albino rabbits were randomly, equally divided into two groups and fed pure cholesterol (0.5g/kg body weight/day) for the period of eight weeks to develop hyperlipidemia. Group-I (control) and Group-II received a normal diet with 2 mL normal saline and 2 mL aqueous emulsified TFG seeds powder (500 mg/kg body weight/day) for four weeks, respectively. Lipid profile and weight were measured at baseline after eight weeks and at the end of the study (12 weeks). Atherogenic indices were calculated by Friedewalds formula. Statistical analysis was performed using IBM: SPSS version 20, and student t test was used to compare variables between groups. After eight weeks of study period, cholesterol feeding was discontinued and hyperlipidemic value was compared with the initial baseline data. Significant increase in body weight and lipid profile variables were observed in the two groups, while there was a significant decrease in high-density lipoprotein cholesterol (HDL-C). After the end of the study (12 weeks), the aqueous emulsified fenugreek (TFG) seeds powder reduced significantly the serum total cholesterol, low-density lipoprotein cholesterol (LDL-C), and the atheriogenic index (P < 0.001), with significant increase in the HDL-C (P < 0.001) in experimentally hyperlipidemic rabbits (P < 0.001) as compared to control group, whereas no significant differences were observed in the triglyceride very low-density lipoprotein cholesterol (VLDL-C) and body weight (P > 0.05) of both groups. It was concluded that fenugreek seeds powder had a significant hypolipidemic effect in experimentally-induced hyperlipidemic rabbits.

  4. 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

  5. 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.

  6. 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

  7. 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).

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. 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.

  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. 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.

  7. 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

  8. 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

  9. 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

    Is limited prehospital resuscitation with plasma more beneficial than using a synthetic colloid ? An experimental study in rabbits with parenchymal...with plasma more beneficial than using a synthetic colloid ? An experimental study in rabbits with parenchymal bleeding 5a. CONTRACT NUMBER 5b...subjects with active bleeding compared with a single plasma protein solution (5% albumin) or the synthetic colloid (Hextend) that is currently used on the

  10. [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.

  11. 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

  12. 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

  13. 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.

  14. 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

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. 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

  2. [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)

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. [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.

  10. 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

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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.

  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. 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

  19. 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.

  20. 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.

  1. 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.

  2. [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.

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. 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

  8. [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.

  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. 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.

  11. 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.

  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. 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.

  14. 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

  15. 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

  16. 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

  17. 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

  18. Relation between mechanical stiffness and vibration transmission of fracture callus: an experimental study on rabbit tibia.

    PubMed

    Akkus, O; Korkusuz, F; Akin, S; Akkas, N

    1998-01-01

    It has been suggested that the vibration transmission across a fracture is affected by the stages of healing of the fracture callus. This study aims to correlate the change in vibration transmission with mechanical stiffness of the callus measured by three-point bending. The right tibiae of male, three-month old local albino rabbits were osteotomized and stabilized by intramedullary fixation following open reduction. The intramedullary rods were removed on the 15th, 28th, 42nd and 90th days postoperatively and the tibiae were excised for vibration, three-point bending and bone mineral density analysis by quantitative computerized tomography (QCT). Optimum time for clinical weight bearing was determined by checking the convergence of the vibration parameters of the fractured tibia to those of the unfractured contralateral. The conclusions obtained from curvature analysis, based on vibration experiments, were in considerable correlation (Spearman's rank correlation coefficient r = 0.93, p = 0.003) with the conclusions obtained from the three-point bending test data which reflected the mechanical condition of the bone by direct means. However, no correlation between bone mineral density change and vibration transmission was noted.

  19. [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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. [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.

  14. 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.

  15. 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

  16. [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.

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. [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%.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. [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.

  4. 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

  5. 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

  6. [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.

  7. 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.

  8. [(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.

  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. 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

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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

  3. [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.

  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. 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.

  7. 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

  8. 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).

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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 the study period, one death unrelated to the treatment occurred in the LDE-paclitaxel group and one death occurred in the control group. CONCLUSION: Treatment with LDE-paclitaxel was tolerated by patients with cardiovascular disease and showed the potential to reduce atherosclerotic lesion size. PMID:27626473

  6. 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

  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. Pulsatile Flow Studies in Atherosclerotic Carotid Bifurcations

    NASA Astrophysics Data System (ADS)

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

    2001-11-01

    Particle image velocimetry and flow visualization techniques are used to study flows in models of atherosclerotic carotid bifurcations. The flow models exactly replicate the interior geometry of plaque excised from patients. The input flows are physiological wave forms derived from Doppler Ultrasound scans done on patients before surgery. The systolic and diastolic Reynolds numbers are 300 and 900. The complex internal geometry of the diseased artery combined with the pulsatile input flow results in exceedingly complex flow patterns. These flow patterns include internal jets, three-dimensional shear layers, stagnation lines, and multiple recirculation and separation regions. The physiological input flows are compared to flows when the wave form is sinusoidal.

  9. Endovascular revascularization for aortoiliac atherosclerotic disease

    PubMed Central

    Aggarwal, Vikas; Waldo, Stephen W; Armstrong, Ehrin J

    2016-01-01

    Atherosclerotic iliac artery disease is increasingly being treated with endovascular techniques. A number of new stent technologies can be utilized with high long-term patency, including self-expanding stents, balloon-expandable stents, and covered stents, but comparative data on these stent types and in more complex lesions are lacking. This article provides a review of currently available iliac stent technologies, as well as complex procedural aspects of iliac artery interventions, including approaches to the treatment of iliac bifurcation disease, long segment occlusions, choice of stent type, and treatment of iliac artery in-stent restenosis. PMID:27099509

  10. Atherosclerotic renal artery stenosis: Current status

    PubMed Central

    Kwon, Soon Hyo; Lerman, Lilach O.

    2014-01-01

    Atherosclerotic renal artery stenosis (ARAS) remains a major cause of secondary hypertension and renal failure. Randomized, prospective trials show that medical treatment should constitute the main therapeutic approach in ARAS. Regardless of intensive treatment and adequate blood pressure control, however, renal and extra-renal complications are not uncommon. Yet, the precise mechanisms, accurate detection, and optimal treatment in ARAS remain elusive. Strategies oriented to early detection and targeting these pathogenic pathways might prevent development of clinical endpoints. Here, we review the results of recent clinical trials, current understanding of the pathogenic mechanisms, novel imaging techniques to assess renal damage in ARAS, and treatment options. PMID:25908472

  11. Ultrafast optical-ultrasonic system and miniaturized catheter for imaging and characterizing atherosclerotic plaques in vivo

    PubMed Central

    Li, Jiawen; Ma, Teng; Mohar, Dilbahar; Steward, Earl; Yu, Mingyue; Piao, Zhonglie; He, Youmin; Shung, K. Kirk; Zhou, Qifa; Patel, Pranav M.; Chen, Zhongping

    2015-01-01

    Atherosclerotic coronary artery disease (CAD) is the number one cause of death worldwide. The majority of CAD-induced deaths are due to the rupture of vulnerable plaques. Accurate assessment of plaques is crucial to optimize treatment and prevent death in patients with CAD. Current diagnostic techniques are often limited by either spatial resolution or penetration depth. Several studies have proved that the combined use of optical and ultrasonic imaging techniques increase diagnostic accuracy of vulnerable plaques. Here, we introduce an ultrafast optical-ultrasonic dual-modality imaging system and flexible miniaturized catheter, which enables the translation of this technology into clinical practice. This system can perform simultaneous optical coherence tomography (OCT)-intravascular ultrasound (IVUS) imaging at 72 frames per second safely in vivo, i.e., visualizing a 72 mm-long artery in 4 seconds. Results obtained in atherosclerotic rabbits in vivo and human coronary artery segments show that this ultrafast technique can rapidly provide volumetric mapping of plaques and clearly identify vulnerable plaques. By providing ultrafast imaging of arteries with high resolution and deep penetration depth simultaneously, this hybrid IVUS-OCT technology opens new and safe opportunities to evaluate in real-time the risk posed by plaques, detect vulnerable plaques, and optimize treatment decisions. PMID:26678300

  12. 13C MAS NMR studies of crystalline cholesterol and lipid mixtures modeling atherosclerotic plaques.

    PubMed Central

    Guo, W; Hamilton, J A

    1996-01-01

    Cholesterol and cholesteryl esters are the predominant lipids of atherosclerotic plaques. To provide fundamental data for the quantitative study of plaque lipids in situ, crystalline cholesterol (CHOL) and CHOL/cholesteryl ester (CE) mixtures with other lipids were studied by solid-state nuclear magnetic resonance with magic-angle-sample spinning. Highly distinctive spectra for three different crystalline structures of CHOL were obtained. When CHOL crystals were mixed with isotropic CE oil, solubilized CHOL (approximately 13 mol % CHOL) was detected by characteristic resonances such as C5, C6, and C3; the excess crystalline CHOL (either anhydrous or monohydrate) remained in its original crystalline structure, without being affected by the coexisting CE. By use of 13C-enriched CHOL, the solubility of CHOL in the CE liquid-crystalline phase (approximately 8 mol %) was measured. When phosphatidylcholine was hydrated in presence of CHOL and CE, magic-angle-sampling nuclear magnetic resonance revealed liquid-crystalline CHOL/phosphatidylcholine multilayers with approximately an equal molar ratio of CHOL/phosphatidylcholine. Excess CHOL existed in the monohydrate crystalline form, and CE in separate oil or crystalline phases, depending on the temperature. The magic-angle-sampling nuclear magnetic resonance protocol for identifying different lipid phases was applied to intact (ex vivo) atherosclerotic plaques of cholesterol-fed rabbits. Liquid, liquid-crystalline, and solid phases of CE were characterized. Images FIGURE 2 PMID:8913623

  13. The vulnerable and unstable atherosclerotic plaque.

    PubMed

    Fishbein, Michael C

    2010-01-01

    The lesion responsible for the overwhelming majority of acute coronary events is plaque disruption or erosion with superimposed thrombosis. The term "vulnerable plaque" has been used to describe those atherosclerotic plaques that are particularly susceptible to disruption. Vulnerable plaques are generally characterized as those having a thin inflamed fibrous cap over a very large lipid core. However, only a small percentage of such plaques rupture, and plaques with different characteristics may also rupture and thrombose. Most autopsy, intravascular ultrasound, and recent computed tomography angiographic studies of coronary arteries reveal large plaques at sites of rupture. While angiographic data are said to show less severe narrowing at sites of plaque rupture, actual review of data indicates that, even angiographically, more than 50% of plaques have greater than 75% cross-sectional area stenosis at sites of plaque rupture. If plaque rupture is more common at the shoulder region of a plaque, one could envision that this would be at a peripheral site of the plaque where the plaque may not be as large or occlusive. New knowledge about vulnerable plaques is emerging through the evolution of novel techniques used to study plaques in vivo. These methods combine sophisticated imaging techniques, often in conjunction with molecular biomarkers, that provide new insights into plaque biology. Since atherosclerotic coronary artery disease is such a widespread and fatal disease, it is important that we continue to strive for a greater understanding of the nature of the vulnerable plaque. Only then can rational interventions for this disorder be developed and implemented.

  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. Variant rabbit hemorrhagic disease virus in young rabbits, Spain.

    PubMed

    Dalton, Kevin P; Nicieza, Inés; Balseiro, Ana; Muguerza, María A; Rosell, Joan M; Casais, Rosa; Álvarez, Ángel L; Parra, Francisco

    2012-12-01

    Outbreaks of rabbit hemorrhagic disease have occurred recently in young rabbits on farms on the Iberian Peninsula where rabbits were previously vaccinated. Investigation identified a rabbit hemorrhagic disease virus variant genetically related to apathogenic rabbit caliciviruses. Improved antivirus strategies are needed to slow the spread of this pathogen.

  16. 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.

  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. 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.

  19. 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

  20. 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).

  1. 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

  2. [From myocardium to the atherosclerotic plaque: new perspectives in cardiologic imaging].

    PubMed

    Gargiulo, Paola; D'Amore, Carmen; Dellegrottaglie, Santo; Leosco, Dario; Rengo, Giuseppe; Musella, Francesca; Pirozzi, Elisabetta; Mosca, Susanna; Casaretti, Laura; Formisano, Roberto; Bologna, Ada; Parente, Antonio; Conte, Sirio; Perrone-Filardi, Pasquale

    2011-06-01

    Molecular imaging is an innovative and promising approach in cardiology for functional characterization of atherosclerosis. Nuclear, ultrasound and magnetic resonance imaging have been used for assessment of atherosclerosis of large and small arteries in several clinical and experimental studies. Positron Emission Tomography with fluorodeoxyglucose can measure metabolic activity and vulnerability of atherosclerotic plaques, identifying individuals at risk of future cardiovascular events. Magnetic resonance imaging can quantify carotid artery inflammation using iron oxide nanoparticles as contrast agent. In addition, macrophage accumulation of iron particles in atherosclerotic plaques may allow monitoring of inflammation during drug therapy, whereas contrast-enhanced ultrasound imaging may detect plaque neovascularization. Currently, technical factors, including cardiac and diaphragmatic motion and small size of coronary vessels, limit routine application of these techniques for coronary imaging. Purpose of this review is to describe state of the art and potential areas of clinical applications of molecular imaging of atherosclerosis.

  3. Gene expression in macrophage-rich human atherosclerotic lesions. 15-lipoxygenase and acetyl low density lipoprotein receptor messenger RNA colocalize with oxidation specific lipid-protein adducts.

    PubMed Central

    Ylä-Herttuala, S; Rosenfeld, M E; Parthasarathy, S; Sigal, E; Särkioja, T; Witztum, J L; Steinberg, D

    1991-01-01

    Oxidatively modified low density lipoprotein (LDL) exhibits several potentially atherogenic properties, and inhibition of LDL oxidation in rabbits decreases the rate of the development of atherosclerotic lesions. In vitro studies have suggested that cellular lipoxygenases may be involved in LDL oxidation, and we have shown previously that 15-lipoxygenase and oxidized LDL are present in rabbit atherosclerotic lesions. We now report that epitopes of oxidized LDL are also found in macrophage-rich areas of human fatty streaks as well as in more advanced human atherosclerotic lesions. Using in situ hybridization and immunostaining techniques, we also report that 15-lipoxygenase mRNA and protein colocalize to the same macrophage-rich areas. Moreover, these same lesions express abundant mRNA for the acetyl LDL receptor but no detectable mRNA for the LDL receptor. We suggest that atherogenesis in human arteries may be linked to macrophage-induced oxidative modification of LDL mediated by 15-lipoxygenase, leading to subsequent enhanced macrophage uptake, partly by way of the acetyl LDL receptor. Images PMID:2010531

  4. The European rabbit (Oryctolagus cuniculus), a source of zoonotic cryptosporidiosis.

    PubMed

    Robinson, G; Chalmers, R M

    2010-12-01

    Cryptosporidium spp. have been found in the faeces of over 150 mammalian host species, but the risks to public health from wildlife are poorly understood. In summer 2008, the Cryptosporidium sp. rabbit genotype was identified as the aetiological agent in an outbreak of waterborne human cryptosporidiosis. The source was a wild rabbit that had entered a treated water tank. To establish current knowledge about Cryptosporidium spp. infecting lagomorphs, especially the host range and biological characteristics of the rabbit genotype, and the potential risks to public health that rabbits may pose in the transmission of zoonotic cryptosporidiosis, we undertook a literature and data review. The literature returned demonstrates that although the European rabbit (Oryctolagus cuniculus) has been the most widely studied lagomorph, few large scale studies were found. The prevalence of Cryptosporidium spp. in wild rabbit populations in the two large scale studies was 0.9% (95%CI 0.2-5.0) and 0.0% (95%CI 0.0-1.6). Neither study provided age nor sex profiles nor typing of Cryptosporidium isolates. The infecting Cryptosporidium species was confirmed in just four other studies of rabbits, all of which showed the rabbit genotype. Human-infectious Cryptosporidium species including Cryptosporidium parvum have caused experimental infections in rabbits and it is likely that this may also occur naturally. No published studies of the host range and biological features of the Cryptosporidium rabbit genotype were identified, but information was generated on the identification and differentiation of the rabbit genotype at various genetic loci. Both pet and wild rabbits are a potential source of human cryptosporidiosis and as such, good hygiene practices are recommended during and after handling rabbits or exposure to their faeces, or potentially contaminated surfaces. Water supplies should be protected against access by wildlife, including rabbits.

  5. Micro-morphometrical assessment of the effect of Harpagophytum procumbens extract on articular cartilage in rabbits with experimental osteoarthritis using magnetic resonance imaging.

    PubMed

    Wachsmuth, L; Lindhorst, E; Wrubel, S; Hadzhiyski, H; Hudelmaier, M; Eckstein, F; Chrubasik, S

    2011-08-01

    In vitro effects indicate a putative beneficial effect of Harpagophytum procumbens on cartilage turnover, however, in vivo protective effects on cartilage have yet to be demonstrated. A 7.1T MRI scanner was used to derive measurements of thickness, surface area and volume of the tibial condylar cartilage and to assess their precision (in the case of volume also accuracy) against the volumes of dissected cartilage measured by water displacement. Quantitative measurements were made in 16 rabbits, 6 months after unilateral medial meniscectomy and transection of the anterior cruciate ligament, after which eight of these were given a proprietary extract of Harpagophytum procumbens (HP). A semiquantitative MRI-based grading of the tibial cartilage was also compared with a 'macroscopic' grading based on direct visual inspection of dissected joints. The test-retest precision for MRI-based measurement was ≤6.4%. MRI-based measurements correlated well with volumes of surgically resected cartilage (r =  0.97, pair-wise random difference 4.2%). The medial tibial cartilage thickness and volume were about 35% smaller in the operated knees than in the non-operated contralateral knees (p < 0.05). The findings suggest that MRI is a precise and accurate tool for evaluating cartilage in a rabbit model of OA. The difference between the intact and operated knee in thickness and volume of the medial tibial cartilage was slightly but not significantly smaller in the HP-treated group than in the non-treated group.

  6. Metabolic syndrome-associated sperm alterations in an experimental rabbit model: relation with metabolic profile, testis and epididymis gene expression and effect of tamoxifen treatment.

    PubMed

    Marchiani, Sara; Vignozzi, Linda; Filippi, Sandra; Gurrieri, Bruna; Comeglio, Paolo; Morelli, Annamaria; Danza, Giovanna; Bartolucci, Gianluca; Maggi, Mario; Baldi, Elisabetta

    2015-02-05

    The influence of metabolic syndrome (MetS) on sperm quality and function is debated. Using a well-established high fat diet (HFD) rabbit model resembling human MetS, including development of hypogonadism, we demonstrate that HFD decreased sperm motility, morphology and acrosome reaction in response to progesterone and increased sperm cholesterol content. All the above parameters were associated with most MetS features, its severity and plasma testosterone (T) at univariate analysis. After T adjustment, sperm morphology and motility retained a significant association, respectively, with mean arterial pressure and circulating cholesterol levels. MetS modified the expression of inflammatory and tissue remodelling genes in the testis and of aquaporins in the epididymis. In a multivariate analysis, sperm morphology resulted associated with testis expression of fibronectin and collagen type 1 genes, whereas motility with epididymis aquaporin 1 gene. Administration of tamoxifen, used in the treatment of idiopathic male infertility, to HFD rabbits partially restored motility, but further decreased morphology and increased spontaneous acrosome reaction, without restoring responsiveness to progesterone. Overall our results indicate that development of MetS produces detrimental effects on sperm quality and functionality by inducing metabolic disorders leading to alterations in testis and epididymis functions and evidence a role of hypertension as a new determinant of abnormal sperm morphology, in line with a previous human study from our group.

  7. Host tissue reactions of non-demineralized autogenic and xenogenic dentin blocks implanted in a non-osteogenic environment. An experimental study in rabbits.

    PubMed

    Al-Asfour, Adel; Farzad, Payam; Andersson, Lars; Joseph, Bobby; Dahlin, Christer

    2014-06-01

    Dentoalveolar ankylosis with osseous replacement is often seen after replantation of avulsed teeth, and this process may be used for preservation of alveolar crests after trauma. Its exact mechanisms with regard to osteoinductive properties are not yet fully understood and need to be systematically investigated. Dentin can possibly act as a slow-releasing carrier of bone morphogenic proteins (BMP), and this property of dentin has been proposed to be used as an alternative or supplement to bone grafting in the maxillofacial region. We aimed to initially asses host tissue reactions to dentin by implanting dentin blocks of autogenic and xenogenic human origin in rabbit connective tissue of the abdominal wall and femoral muscle. Animals were sacrificed after a period of 3 months, and histological processing, sectioning and examinations were carried out. Bone formation, cell counts and thickness of capsule surrounding the grafts were evaluated. Only minor signs of heterotopic bone formation were seen. There were no significant differences between autografts and xenografts or grafts implanted in connective tissue or muscle with regards to tissue reactions except for a significant difference (P = 0.018) in findings of more local inflammatory cells in relation to grafts placed in connective tissue in the autograft group. We conclude that during the time frame of this study, non-demineralized dentin, whether autogenous or xenogenic did not have the potential to induce bone formation when implanted in non-osteogenic areas such as the abdominal wall and abdominal muscle of rabbits.

  8. Role of guided bone regeneration principle in preventing fibrous healing in distraction osteogenesis at high speed: experimental study in rabbit mandibles.

    PubMed

    Elshahat, Ahmed; Inoue, Nozomu; Marti, Guy; Safe, Ikram; Manson, Paul; Vanderkolk, Craig

    2004-11-01

    The formation of fibrous tissues at the distraction gap may result from the accumulation of rapidly migrating fibroblasts at the site of an osteotomy, especially when distraction is rapid. Addition of osteopromotive membranes could theoretically prevent fibroblasts from entering the distraction gap, allowing the osteotomy site to be filled with only osteogenic cells. This study is an attempt to achieve a rapid successful distraction without fibrosis through the use of collagen membranes. Sixteen skeletally mature New Zealand white rabbits were used in this study. They were divided into two groups. One rabbit from each group was excluded from the study because of dislodgement of the distractors. In one group (n = 7), distraction was done as usual. In the other group (n = 7), a collagen membrane surrounded the osteotomy site to be distracted. After a 7-day latency period, distraction started at a rate 2 mm once per day for 5 days. The distractor was left in place for 4 weeks to allow consolidation. Results showed osteogenesis in both groups. Whereas addition of the membrane to distraction increased the quantity of bone formed, absence of the membrane allowed early mineralization (better quality of bone regarding the density). Neither of the two groups showed significant fibrosis or cartilage formation. The endosteum served as a source of blood supply when the periosteum was excluded. The periosteum served as a membrane for guided bone regeneration. Membranes for guided bone regeneration can be used with distraction when the periosteum is lost from trauma or is broken from fast distraction.

  9. Safety and Biocompatibility of a New High-Density Polyethylene-Based Spherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits

    PubMed Central

    Fernandez-Bueno, Ivan; Di Lauro, Salvatore; Alvarez, Ivan; Lopez, Jose Carlos; Garcia-Gutierrez, Maria Teresa; Fernandez, Itziar; Larra, Eva; Pastor, Jose Carlos

    2015-01-01

    Purpose. To evaluate clinically and histologically the safety and biocompatibility of a new HDPE-based spherical porous orbital implants in rabbits. Methods. MEDPOR (Porex Surgical, Inc., Fairburn, GA, USA), OCULFIT I, and OCULFIT II (AJL Ophthalmic S.A., Vitoria, Spain) implants were implanted in eviscerated rabbis. Animals were randomly divided into 6 groups (n = 4 each) according to the 3 implant materials tested and 2 follow-up times of 90 or 180 days. Signs of regional pain and presence of eyelid swelling, conjunctival hyperemia, and amount of exudate were semiquantitatively evaluated. After animals sacrifice, the implants and surrounding ocular tissues were processed for histological staining and polarized light evaluation. Statistical study was performed by ANOVA and Kaplan-Meier analysis. Results. No statistically significant differences in regional pain, eyelid swelling, or conjunctival hyperemia were shown between implants and/or time points evaluated. However, amount of exudate differed, with OCULFIT I causing the smallest amount. No remarkable clinical complications were observed. Histological findings were similar in all three types of implants and agree with minor inflammatory response. Conclusions. OCULFIT ophthalmic tolerance and biocompatibility in rabbits were comparable to the clinically used MEDPOR. Clinical studies are needed to determine if OCULFIT is superior to the orbital implants commercially available. PMID:26689343

  10. Atherosclerotic plaque regression: fact or fiction?

    PubMed

    Shanmugam, Nesan; Román-Rego, Ana; Ong, Peter; Kaski, Juan Carlos

    2010-08-01

    Coronary artery disease is the major cause of death in the western world. The formation and rapid progression of atheromatous plaques can lead to serious cardiovascular events in patients with atherosclerosis. The better understanding, in recent years, of the mechanisms leading to atheromatous plaque growth and disruption and the availability of powerful HMG CoA-reductase inhibitors (statins) has permitted the consideration of plaque regression as a realistic therapeutic goal. This article reviews the existing evidence underpinning current therapeutic strategies aimed at achieving atherosclerotic plaque regression. In this review we also discuss imaging modalities for the assessment of plaque regression, predictors of regression and whether plaque regression is associated with a survival benefit.

  11. Pulsatile Flow Studies in Atherosclerotic Carotid Bifurcation

    NASA Astrophysics Data System (ADS)

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

    2002-11-01

    Particle image velocimetry and flow visualization techniques are used to study flow in models of atherosclerotic carotid bifurcations. The models exactly replicate the interior geometry of plaque excised from patients. The input flow is a physiological waveform derived from Doppler Ultrasound scans done on the patients before surgery. The systolic and diastolic Reynolds numbers are 200 and 900 respectively. The complex internal geometry of the diseased artery combined with the pulsatile input flows give exceedingly complex flow patterns. These flow patterns include internal jets, three-dimensional shear layers, stagnation lines, and multiple recirculation and separation regions. Ensemble averaged and instantaneous flow fields are compared. Wall shear stresses at the stenoses are estimated to be on the order of 10 PA. The physiological input flows are also compared to flows when the waveform is sinusoidal.

  12. Potential Anti-Atherosclerotic Properties of Astaxanthin

    PubMed Central

    Kishimoto, Yoshimi; Yoshida, Hiroshi; Kondo, Kazuo

    2016-01-01

    Astaxanthin is a naturally occurring red carotenoid pigment classified as a xanthophyll, found in microalgae and seafood such as salmon, trout, and shrimp. This review focuses on astaxanthin as a bioactive compound and outlines the evidence associated with its potential role in the prevention of atherosclerosis. Astaxanthin has a unique molecular structure that is responsible for its powerful antioxidant activities by quenching singlet oxygen and scavenging free radicals. Astaxanthin has been reported to inhibit low-density lipoprotein (LDL) oxidation and to increase high-density lipoprotein (HDL)-cholesterol and adiponectin levels in clinical studies. Accumulating evidence suggests that astaxanthin could exert preventive actions against atherosclerotic cardiovascular disease (CVD) via its potential to improve oxidative stress, inflammation, lipid metabolism, and glucose metabolism. In addition to identifying mechanisms of astaxanthin bioactivity by basic research, much more epidemiological and clinical evidence linking reduced CVD risk with dietary astaxanthin intake is needed. PMID:26861359

  13. Nuclear Molecular Imaging for Vulnerable Atherosclerotic Plaques

    PubMed Central

    Lee, Soo Jin

    2015-01-01

    Atherosclerosis is an inflammatory disease as well as a lipid disorder. Atherosclerotic plaque formed in vessel walls may cause ischemia, and the rupture of vulnerable plaque may result in fatal events, like myocardial infarction or stroke. Because morphological imaging has limitations in diagnosing vulnerable plaque, molecular imaging has been developed, in particular, the use of nuclear imaging probes. Molecular imaging targets various aspects of vulnerable plaque, such as inflammatory cell accumulation, endothelial activation, proteolysis, neoangiogenesis, hypoxia, apoptosis, and calcification. Many preclinical and clinical studies have been conducted with various imaging probes and some of them have exhibited promising results. Despite some limitations in imaging technology, molecular imaging is expected to be used both in the research and clinical fields as imaging instruments become more advanced. PMID:26357491

  14. Ophthalmic masquerades of the atherosclerotic carotids

    PubMed Central

    Arthur, Anupriya; Alexander, Anika; Bal, Simerpreet; Sivadasan, Ajith; Aaron, Sanjith

    2014-01-01

    Patients with carotid atherosclerosis can present with ophthalmic symptoms. These symptoms and signs can be due to retinal emboli, hypoperfusion of the retina and choroid, opening up of collateral channels, or chronic hypoperfusion of the globe (ocular ischemic syndrome). These pathological mechanisms can produce many interesting signs and a careful history can bring out important past symptoms pointing toward the carotid as the source of the patient's presenting symptom. Such patients are at high risk for an ischemic stroke, especially in the subsequent few days following their first acute symptom. It is important for clinicians to be familiar with these ophthalmic symptoms and signs caused by carotid atherosclerosis for making an early diagnosis and to take appropriate measures to prevent a stroke. This review elaborates the clinical features, importance, and implications of various ophthalmic symptoms and signs resulting from atherosclerotic carotid artery disease. PMID:24817748

  15. Subsurface ablation of atherosclerotic plaque using ultrafast laser pulses

    PubMed Central

    Lanvin, Thomas; Conkey, Donald B.; Frobert, Aurelien; Valentin, Jeremy; Goy, Jean-Jacques; Cook, Stéphane; Giraud, Marie-Noelle; Psaltis, Demetri

    2015-01-01

    We perform subsurface ablation of atherosclerotic plaque using ultrafast pulses. Excised mouse aortas containing atherosclerotic plaque were ablated with ultrafast near-infrared (NIR) laser pulses. Optical coherence tomography (OCT) was used to observe the ablation result, while the physical damage was inspected in histological sections. We characterize the effects of incident pulse energy on surface damage, ablation hole size, and filament propagation. We find that it is possible to ablate plaque just below the surface without causing surface damage, which motivates further investigation of ultrafast ablation for subsurface atherosclerotic plaque removal. PMID:26203381

  16. Subsurface ablation of atherosclerotic plaque using ultrafast laser pulses.

    PubMed

    Lanvin, Thomas; Conkey, Donald B; Frobert, Aurelien; Valentin, Jeremy; Goy, Jean-Jacques; Cook, Stéphane; Giraud, Marie-Noelle; Psaltis, Demetri

    2015-07-01

    We perform subsurface ablation of atherosclerotic plaque using ultrafast pulses. Excised mouse aortas containing atherosclerotic plaque were ablated with ultrafast near-infrared (NIR) laser pulses. Optical coherence tomography (OCT) was used to observe the ablation result, while the physical damage was inspected in histological sections. We characterize the effects of incident pulse energy on surface damage, ablation hole size, and filament propagation. We find that it is possible to ablate plaque just below the surface without causing surface damage, which motivates further investigation of ultrafast ablation for subsurface atherosclerotic plaque removal.

  17. The relative proportions of IgG-, IgA- and IgM-containing cells in rabbit tissues during experimental trichinosis

    PubMed Central

    Crandall, R. B.; Cebra, J. J.; Crandall, C. A.

    1967-01-01

    The relative proportions of IgG, IgM and IgA immunoglobulin-containing cells were determined in the intestinal mucosa, spleen, popliteal lymph nodes and diaphragm of rabbits after a single infection and after hyperinfection with Trichinella spiralis. Staining with pairs of immunofluorescent reagents, specifically reactive with γ, μ or α immunoglobulin heavy chains and labelled with contrasting fluorochromes, permitted direct counting of cells containing two different immunoglobulin classes in a single tissue section. By employing two different pairs of reagents on adjacent sections the relative numbers of cells containing IgG, IgM and IgA were calculated. The observed cellular distribution of γ, μ and α heavy chains in the rabbit intestinal mucosa corresponded with the reported distribution in the human intestine. A relative increase in IgM-containing cells in the mucosa was observed after early infection with Trichinella, followed by an apparent increase in cells with IgG late in infection and after hyperinfection. The proportion of cells staining for IgA remained uniformly high in the intestine throughout the course of infection. The proportions of cells containing different immunoglobulin classes in the spleen contrasted with those observed in the intestinal mucosa, particularly with respect to cells containing α chain. IgA cells made up 2–10 per cent of the immunoglobulin-containing cells in the spleen as compared to 80–90 per cent in the intestinal mucosa. Most spleen sections showed an increase in IgM cells late in infection with Trichinella and after hyperinfection. The proportions of immunoglobulin-containing cells in the popliteal lymph nodes generally paralleled those observed in the spleen. Local cellular infiltration of the diaphragm occurred at the time of larval encystment. Immunoglobulin-containing cells were often prominent and the cellular distribution of immunoglobulin classes resembled that found in the spleen. The indirect fluorescent

  18. On Studying the Interaction Between Different Stent Models and Rabbit Tracheal Tissue: Numerical, Endoscopic and Histological Comparison.

    PubMed

    Chaure, J; Serrano, C; Fernández-Parra, R; Peña, E; Lostalé, F; De Gregorio, M A; Martínez, M A; Malvè, M

    2016-02-01

    Stenting technique is employed worldwide for treating atherosclerotic vessel and tracheal stenosis. Both diseases can be treated by means of metallic stents which present advantages but are affected by the main problem of restenosis of the stented area. In this study we have built a rabbit trachea numerical model and we have analyzed it before and after insertion and opening of two types of commercial stent: a Zilver(®) Flex™ Stent and a WallStent™. In experimental parallel work, two types of stent were implanted in 30 New Zealand rabbits divided in two groups of 10 animals corresponding to each stent type and a third group made up of 10 animals without stent. The tracheal wall response was assessed by means of computerized tomography by endoscopy, macroscopic findings and histopathological study 90 days after stent deployment. Three idealized trachea models, one model for each group, were created in order to perform the computational study. The animal model was used to validate the numerical findings and to attempt to find qualitative correlations between numerical and experimental results. Experimental findings such as inflammation, granuloma and abnormal tissue growth, assessed from histomorphometric analyses were compared with derived numerical parameters such as wall shear stress (WSS) and maximum principal stress. The direct comparison of these parameters and the biological response supports the hypothesis that WSS and tensile stresses may lead to a greater tracheal epithelium response within the stented region, with the latter seeming to have the dominant role. This study may be helpful for improving stent design and demonstrates the feasibility offered by in-silico investigated tracheal structural and fluid dynamics.

  19. The role of stainless steel wire mesh and cement in bone allograft incorporation in impaction grafting technique: an experimental study in rabbits.

    PubMed

    Roidis, Nikolaos; Karachalios, Theofilos; Khaldi, Lubna; Stamos, Konstantinos; Lyritis, George P

    2003-06-01

    Cages of flexible stainless steel wire mesh were filled with impacted morcellized cancellous allograft. Bone defects were created in both tibial metaphyseal regions of 10 adult white New Zealand rabbits. The base of both defects was plugged with a small amount of bone cement. The cages were implanted in the right tibia while the left tibia was filled with impacted bone allograft. Histologic and histomorphometric evaluation of the retrieved specimens at 3 months showed a statistically significant difference in active bone formation parameters between the 2 groups. Active bone formation was more prominent away from the bone cement. The biological process of bone graft incorporation in the "impaction grafting" technique seems to be adversely affected by stainless steel wire mesh and in areas adjacent to bone cement.

  20. A New Safety Concern for Glaucoma Treatment Demonstrated by Mass Spectrometry Imaging of Benzalkonium Chloride Distribution in the Eye, an Experimental Study in Rabbits

    PubMed Central

    Brignole-Baudouin, Françoise; Desbenoit, Nicolas; Hamm, Gregory; Liang, Hong; Both, Jean-Pierre; Brunelle, Alain; Fournier, Isabelle; Guerineau, Vincent; Legouffe, Raphael; Stauber, Jonathan; Touboul, David; Wisztorski, Maxence; Salzet, Michel; Laprevote, Olivier; Baudouin, Christophe

    2012-01-01

    We investigated in a rabbit model, the eye distribution of topically instilled benzalkonium_(BAK) chloride a commonly used preservative in eye drops using mass spectrometry imaging. Three groups of three New Zealand rabbits each were used: a control one without instillation, one receiving 0.01%BAK twice a day for 5 months and one with 0.2%BAK one drop a day for 1 month. After sacrifice, eyes were embedded and frozen in tragacanth gum. Serial cryosections were alternately deposited on glass slides for histological (hematoxylin-eosin staining) and immunohistological controls (CD45, RLA-DR and vimentin for inflammatory cell infiltration as well as vimentin for Müller glial cell activation) and ITO or stainless steel plates for MSI experiments using Matrix-assisted laser desorption ionization time-of-flight. The MSI results were confirmed by a round-robin study on several adjacent sections conducted in two different laboratories using different sample preparation methods, mass spectrometers and data analysis softwares. BAK was shown to penetrate healthy eyes even after a short duration and was not only detected on the ocular surface structures, but also in deeper tissues, especially in sensitive areas involved in glaucoma pathophysiology, such as the trabecular meshwork and the optic nerve areas, as confirmed by images with histological stainings. CD45-, RLA-DR- and vimentin-positive cells increased in treated eyes. Vimentin was found only in the inner layer of retina in normal eyes and increased in all retinal layers in treated eyes, confirming an activation response to a cell stress. This ocular toxicological study confirms the presence of BAK preservative in ocular surface structures as well as in deeper structures involved in glaucoma disease. The inflammatory cell infiltration and Müller glial cell activation confirmed the deleterious effect of BAK. Although these results were obtained in animals, they highlight the importance of the safety-first principle for

  1. A new safety concern for glaucoma treatment demonstrated by mass spectrometry imaging of benzalkonium chloride distribution in the eye, an experimental study in rabbits.

    PubMed

    Brignole-Baudouin, Françoise; Desbenoit, Nicolas; Hamm, Gregory; Liang, Hong; Both, Jean-Pierre; Brunelle, Alain; Fournier, Isabelle; Guerineau, Vincent; Legouffe, Raphael; Stauber, Jonathan; Touboul, David; Wisztorski, Maxence; Salzet, Michel; Laprevote, Olivier; Baudouin, Christophe

    2012-01-01

    We investigated in a rabbit model, the eye distribution of topically instilled benzalkonium_(BAK) chloride a commonly used preservative in eye drops using mass spectrometry imaging. Three groups of three New Zealand rabbits each were used: a control one without instillation, one receiving 0.01%BAK twice a day for 5 months and one with 0.2%BAK one drop a day for 1 month. After sacrifice, eyes were embedded and frozen in tragacanth gum. Serial cryosections were alternately deposited on glass slides for histological (hematoxylin-eosin staining) and immunohistological controls (CD45, RLA-DR and vimentin for inflammatory cell infiltration as well as vimentin for Müller glial cell activation) and ITO or stainless steel plates for MSI experiments using Matrix-assisted laser desorption ionization time-of-flight. The MSI results were confirmed by a round-robin study on several adjacent sections conducted in two different laboratories using different sample preparation methods, mass spectrometers and data analysis softwares. BAK was shown to penetrate healthy eyes even after a short duration and was not only detected on the ocular surface structures, but also in deeper tissues, especially in sensitive areas involved in glaucoma pathophysiology, such as the trabecular meshwork and the optic nerve areas, as confirmed by images with histological stainings. CD45-, RLA-DR- and vimentin-positive cells increased in treated eyes. Vimentin was found only in the inner layer of retina in normal eyes and increased in all retinal layers in treated eyes, confirming an activation response to a cell stress. This ocular toxicological study confirms the presence of BAK preservative in ocular surface structures as well as in deeper structures involved in glaucoma disease. The inflammatory cell infiltration and Müller glial cell activation confirmed the deleterious effect of BAK. Although these results were obtained in animals, they highlight the importance of the safety-first principle for

  2. Post-traumatic avascular necrosis of the femoral head predicted by preoperative technetium-99m antimony-colloid scan: an experimental and clinical study. [Rabbits; patients

    SciTech Connect

    Turner, J.H.

    1983-07-01

    Technetium-99m antimony colloid was used to visualize the bone marrow of the head of the femur within twenty-four hours after interruption of the blood supply by subcapital osteotomy and section of the ligamentum teres in thirteen rabbits and within twenty-four hours after a subcapital fracture in thirty patients. Of the rabbits, all showed loss of marrow radioactivity over the affected femoral head. Bone-imaging with technetium-99m methylene diphosphonate, in contrast, failed to demonstrate any abnormality in the avascular head of the femur for as long as forty-eight hours after osteotomy. This difference between the marrow scan and the bone scan was attributed to earlier loss of function in the marrow cells than in the osteocytes. The thirty patients who had a preoperative scan within twenty-four hours after sustaining a subcapital fracture were treated by internal fixation with a Richards screw and plate and were followed for as long as two years, or until the patient died or radiographs showed evidence of avascular necrosis. The preoperative technetium-99m antimony-colloid activity in the head of the fractured femur was normal in sixteen patients and absent in fourteen; two of the fourteen had no activity in either hip, which precluded assessment of the fractured hip in these patients. In fifteen of the sixteen hips, preservation of the uptake in the marrow of the head of the fractured femur preoperatively predicted normal healing. Late segmental collapse developed in the remaining hip. In eleven of the twelve patients who had loss of marrow activity in the femoral head preoperatively, avascular necrosis developed within two years.

  3. Hypocholesterolemic and antiatherosclerotic effect of artemisia aucheri in hypercholesterolemic rabbits.

    PubMed

    Dinani, N Jafari; Asgary, Asgary; Madani, H; Naderi, Gh; Mahzoni, P

    2010-07-01

    Atherosclerosis which results from gradual deposition of lipids in arteries is a leading cause of mortality worldwide. Diet is one of the most important factors underlying atherosclerosis. High-cholesterol diets enhance atherosclerosis and vegetarian diets are known to slow down the process. Artemisia aucheri is an herb of the Composite family. Many species of Artemisia have proven hypolipidemic and antioxidant properties. This study determine the effects of Artemisia aucheri on lipoproteins and atherosclerosis in hypercholesterolemic rabbits. Fifteen male rabbits were randomly divided into three groups. Normal diet group, high-cholesterol diet group (1% cholesterol) and Artemisia aucheri group (1% cholesterol diet supplemented with 100 mg/kg body weight the Artemisi aucheri every other day). Biochemical factors were measured at the start, end of the first and second months of the study. At the end of the study, the aorta were removed for assessment of atherosclerotic plaques. The results indicate that Artemisia aucheri significantly reduced the level of total cholesterol, LDL cholesterol and triglycerids and increased HDL cholesterol. The degree of atherosclerotic thickness was significantly reduced in the treated group. Therefore, Artemisia aucheri is one of the useful herbal medicine for preventation of atherosclerosis and more studies in this regard is recommended.

  4. The combined therapy with chondroitin sulfate plus glucosamine sulfate or chondroitin sulfate plus glucosamine hydrochloride does not improve joint damage in an experimental model of knee osteoarthritis in rabbits.

    PubMed

    Roman-Blas, Jorge A; Mediero, Aránzazu; Tardío, Lidia; Portal-Nuñez, Sergio; Gratal, Paula; Herrero-Beaumont, Gabriel; Largo, Raquel

    2017-01-05

    Osteoarthritis is the most common chronic joint disorder especially during aging. Although with controversies, glucosamine, both in its forms of sulfate and hydrochloride, and chondroitin sulfate are commonly employed to treat osteoarthritis. Due to the modest improve in the symptoms observed in patients treated with these drugs alone, a formulation combining both agents has been considered. The discrepant results achieved for pain control or structural improvement in osteoarthritis patients has been attributed to the quality of chemical formulations or different bias in clinical studies. The current study has been designed to test the effects of two different combined formulations with adequate pharmaceutical grade of these drugs in osteoarthritic joints, and to explore the underlying mechanisms modulated by both formulations in different osteoarthritis target tissues. Knee osteoarthritis was surgically induced in experimental rabbits. Some animals received the combined therapy (CT)1, (chondroitin sulfate 1200mg/day + glucosamine sulfate 1500mg/day), or the CT2 ((chondroitin sulfate 1200mg/day + glucosamine hydrochloride 1500mg/day). Neither CT1 nor CT2 significantly modified the cartilage damage or the synovial inflammation observed in osteoarthritic animals. Treatments were also unable to modify the presence of pro-inflammatory mediators, and the synthesis of metalloproteinases in the cartilage or in the synovium of osteoarthritic animals. Combined therapies did not modify the decrease in the subchondral bone mineral density observed in osteoarthritic rabbits. Therapies of chondroitin sulfate plus glucosamine sulfate or chondroitin sulfate plus glucosamine hydrochloride failed to improve structural damage or to ameliorate the inflammatory profile of joint tissues during experimental osteoarthritis.

  5. Rabbit haemorrhagic disease: are Australian rabbits (Oryctolagus cuniculus) evolving resistance to infection with Czech CAPM 351 RHDV?

    PubMed

    Elsworth, P G; Kovaliski, J; Cooke, B D

    2012-11-01

    Rabbit haemorrhagic disease is a major tool for the management of introduced, wild rabbits in Australia. However, new evidence suggests that rabbits may be developing resistance to the disease. Rabbits sourced from wild populations in central and southeastern Australia, and domestic rabbits for comparison, were experimentally challenged with a low 60 ID50 oral dose of commercially available Czech CAPM 351 virus - the original strain released in Australia. Levels of resistance to infection were generally higher than for unselected domestic rabbits and also differed (0-73% infection rates) between wild populations. Resistance was lower in populations from cooler, wetter regions and also low in arid regions with the highest resistance seen within zones of moderate rainfall. These findings suggest the external influences of non-pathogenic calicivirus in cooler, wetter areas and poor recruitment in arid populations may influence the development rate of resistance in Australia.

  6. How to manage hypertension with atherosclerotic renal artery stenosis?

    PubMed

    Ricco, Jean-Baptiste; Belmonte, Romain; Illuminati, Guilio; Barral, Xavier; Schneider, Fabrice; Chavent, Bertrand

    2017-04-01

    The management of atherosclerotic renal artery stenosis (ARAS) in patients with hypertension has been the topic of great controversy. Major contemporary clinical trials such as the Cardiovascular Outcomes for Renal Artery lesions (CORAL) and Angioplasty and Stenting for Renal Atherosclerotic lesions (ASTRAL) have failed to show significant benefit of revascularization over medical management in controlling blood pressure and preserving renal function. We present here the implications and limitations of these trials and formulate recommendations for management of ARAS.

  7. Targeting arterial wall sulfated glycosaminoglycans in rabbit atherosclerosis with a mouse/human chimeric antibody.

    PubMed

    Soto, Yosdel; Mesa, Niurka; Alfonso, Yumisley; Pérez, Arlenis; Batlle, Fernando; Griñán, Tania; Pino, Adonis; Viera, Justo; Frómeta, Milagros; Brito, Victor; Olivera, Armando; Zayas, Francisco; Vázquez, Ana M

    2014-01-01

    The progression of atherosclerosis is favored by increasing amounts of chondroitin sulfate proteoglycans in the artery wall. We previously reported the reactivity of chP3R99 monoclonal antibody (mAb) with sulfated glycosaminoglycans and its association with the anti-atherogenic properties displayed. Now, we evaluated the accumulation of this mAb in atherosclerotic lesions and its potential use as a probe for specific in vivo detection of the disease. Atherosclerosis was induced in NZW rabbits (n = 14) by the administration of Lipofundin 20% using PBS-receiving animals as control (n = 8). Accumulation of chP3R99 mAb in atherosclerotic lesions was assessed either by immunofluorescence detection of human IgG in fresh-frozen sections of aorta, or by immunoscintigraphy followed by biodistribution of the radiotracer upon administration of (99m)Tc-chP3R99 mAb. Immunofluorescence studies revealed the presence of chP3R99 mAb in atherosclerotic lesions 24 h after intravenous administration, whereas planar images showed an evident accumulation of (99m)Tc-chP3R99 mAb in atherosclerotic rabbit carotids. Accordingly, (99m)Tc-chP3R99 mAb uptake by lesioned aortic arch and thoracic segment was increased 5.6-fold over controls and it was 3.9-folds higher in carotids, in agreement with immunoscintigrams. Moreover, the deposition of (99m)Tc-chP3R99 mAb in the artery wall was associated both with the presence and size of the lesions in the different portions of evaluated arteries and was greater than in non-targeted organs. In conclusion, chP3R99 mAb preferentially accumulates in arterial atherosclerotic lesions supporting the potential use of this anti-glycosaminoglycans antibody for diagnosis and treatment of atherosclerosis.

  8. Aldehyde dehydrogenase 2 inhibits inflammatory response and regulates atherosclerotic plaque

    PubMed Central

    Wei, Shu-jian; Zhang, Ming-xiang; Wang, Xu-ping; Yuan, Qiu-huan; Xue, Li; Wang, Jia-li; Cui, Zhao-qiang; Zhang, Yun; Xu, Feng; Chen, Yu-guo

    2016-01-01

    Previous studies demonstrated that aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism, which eliminates ALDH2 activity down to 1%-6%, is a susceptibility gene for coronary disease. Here we investigated the underlying mechanisms based on our prior clinical and experimental studies. Male apoE−/− mice were transfected with GFP, ALDH2-overexpression and ALDH2-RNAi lentivirus respectively (n=20 each) after constrictive collars were placed around the right common carotid arteries. Consequently, ALDH2 gene silencing led to an increased en face plaque area, more unstable plaque with heavier accumulation of lipids, more macrophages, less smooth muscle cells and collagen, which were associated with aggravated inflammation. However, ALDH2 overexpression displayed opposing effects. We also found that ALDH2 activity decreased in atherosclerotic plaques of human and aged apoE−/− mice. Moreover, in vitro experiments with human umbilical vein endothelial cells further illustrated that, inhibition of ALDH2 activity resulted in elevating inflammatory molecules, an increase of nuclear translocation of NF-κB, and enhanced phosphorylation of NF-κB p65, AP-1 c-Jun, Jun-N terminal kinase and p38 MAPK, while ALDH2 activation could trigger contrary effects. These findings suggested that ALDH2 can influence plaque development and vulnerability, and inflammation via MAPK, NF-κB and AP-1 signaling pathways. PMID:27191745

  9. Reduction of Intimal Hyperplasia with Re-188-labeled Stents in a Rabbit Model at 7 and 26 Weeks: An Experimental Study

    SciTech Connect

    Tepe, Gunnar Dietrich, Tobias; Grafen, Franziska; Brehme, Ute; Muschick, Peter; Dinkelborg, Ludger M.; Greschniok, Annette; Claussen, Claus D.; Duda, Stephan H.

    2005-06-15

    The aim of this study was to analyze the feasibility of {sup 188}Re-labeled stents to reduce neointimal formation in a rabbit atherosclerosis model and to test the long-term effects at 7 and 26 weeks. Fifty-nine male New Zealand White rabbits were fed a 0.5% cholesterol diet for 4 weeks before balloon angioplasty and insertion of Palmaz stents in the infrarenal aorta. The animals were sacrificed 7 and 26 weeks after stent implantation. Control stents were compared with {sup 188}Re stents: (dose 1) 11.3 {+-} 1.8 MBq; (dose 2) 37.3 {+-} 4.2 MBq, and (dose 3) 80.1 {+-} 7.8 MBq. Each activity group consisted of a short-term (7 weeks) and a long-term group (26 weeks), resulting in a total of eight study groups. No thrombotic occlusion was observed. The neointimal formation in the control group was 2.11 [95% confidence interval (CI): 0.68-6.52] mm{sup 2} at 7 weeks and 2.10 (0.62-7.11) at 26 weeks. In the treatment groups, neointima reduction was detectable at 7 weeks [dose 1: 0.33 (0.09-1.22) mm{sup 2}; dose 2: 0.17 (0.05-0.57) mm{sup 2}; dose 3: 0.03 (0.01-0.13) mm{sup 2}]. After 26 weeks, a catch-up of neointimal formation in the radioactive groups was most obvious in the low-dose group [dose 1: 0.80 (0.28-2.29) mm{sup 2}; dose 2: 0.18([0.06-0.52) mm{sup 2}; dose 3: 0.50 (0.17-1.42) mm{sup 2}]. Compared to the long-term control group, neointimal reduction was still >60%. No induction of neointimal formation was observed at the edges of the stents. Radiation resulted in delayed re-endothelialization. {sup 188}Re stents were capable to reduce intimal hyperplasia and did not cause thrombosis. The edge effect, which was the major limitation of {sup 32}P stents, was not observed in {sup 188}Re stents.

  10. The Rabbit Corneal Pocket Assay.

    PubMed

    Morbidelli, Lucia; Ziche, Marina

    2016-01-01

    The rabbit corneal micropocket angiogenesis assay uses the avascular cornea as a substrate canvas to study angiogenesis in vivo. Through the use of standardized slow-release pellets, a predictable angiogenic response is generated over the course of 1-2 weeks and then quantified. Uniform slow-release pellets are prepared by mixing purified angiogenic growth factors such as basic fibroblast growth factor or vascular endothelial growth factor and a synthetic polymer to allow slow release. A micropocket is surgically created in the rabbit cornea under anesthesia and a pellet implanted. On the days later, the angiogenic response is measured and qualified using a slit lamp, as well as the concomitant vascular phenotype or inflammatory features. The results of the assay are used to assess the ability of potential therapeutic molecules to modulate angiogenesis in vivo, both when released locally or given by ocular formulations or through systemic treatment. In this chapter, the experimental details of the rabbit cornea assay and technical implementations to the original protocol are described.

  11. Endovascular Treatment of Symptomatic Intracranial Atherosclerotic Disease

    PubMed Central

    Short, Jody L.; Majid, Arshad; Hussain, Syed I.

    2011-01-01

    Symptomatic intracranial atherosclerotic disease (ICAD) is responsible for approximately 10% of all ischemic strokes in the United States. The risk of recurrent stroke may be as high as 35% in patient with critical stenosis >70% in diameter narrowing. Recent advances in medical and endovascular therapy have placed ICAD at the forefront of clinical stroke research to optimize the best medical and endovascular approach to treat this important underlying stroke etiology. Analysis of symptomatic ICAD studies lead to the question that whether angioplasty and/or stenting is a safe, suitable, and efficacious therapeutic strategy in patients with critical stenoses that are deemed refractory to medical management. Most of the currently available data in support of angioplasty and/or stenting in high risk patients with severe symptomatic ICAD is in the form of case series and randomized trial results of endovascular therapy versus medical treatment are awaited. This is a comprehensive review of the state of the art in the endovascular approach with angioplasty and/or stenting of symptomatic ICAD. PMID:21359195

  12. Primary Stenting of Intracranial Atherosclerotic Stenoses

    SciTech Connect

    Straube, T. Stingele, Robert; Jansen, Olav

    2005-04-15

    Purpose: To determine the feasibility and safety of stenting intracranial atherosclerotic stenoses.Methods: In 12 patients the results of primary intracranial stenting were evaluated retrospectively. Patient ages ranged from 49 to 79 years (mean 64 years). Six patients presented with stenoses in the anterior circulation, and six had stenosis in the posterior circulation. One patient presented with extra- and intracranial tandem stenosis of the left internal carotid artery. Three patients presented with acute basilar thrombosis, caused by high-grade basilar stenoses.Results: Intracranial stenoses were successfully stented in 11 of 12 patients. In one patient the stent could not be advanced over the carotid siphon to reach the stenosis of the ophthalmic internal carotid artery. Follow-up digital subtraction angiographic studies were obtained in two patients who had presented with new neurologic signs or symptoms. In both cases the angiogram did not show any relevant stenotic endothelial hyperplasia. In one patient, after local thrombolysis the stenosis turned out to be so narrow that balloon angioplasty had to be performed before stent deployment. All three patients treated for stenosis-related basilar thrombosis died due to brainstem infarction that had ensued before the intervention.Conclusions: Prophylactic primary stenting of intracranial stenoses of the anterior or posterior cerebral circulation can be performed with a low complication rate; technical problems such as stent flexibility must still be solved. Local thrombolysis followed by stenting in stenosis-related thrombotic occlusion is technically possible.

  13. Heat Shock Proteins: Mediators of Atherosclerotic Development.

    PubMed

    Deniset, Justin F; Pierce, Grant N

    2015-01-01

    Heat shock proteins play important housekeeping roles in a variety of cells within the body during normal control conditions. The many different functions for heat shock proteins in the cell depend upon the specific heat shock protein involved. Each protein is nominally differentiated based upon its molecular size. However, in addition to their role in normal cell function, heat shock proteins may play an even more important role as pro-survival proteins conserved through evolution to protect the cell from a variety of stresses. The ability of a cell to withstand these environmental stresses is critical to its capacity to adapt and remain viable. Loss of this ability may lead to pathological states. Abnormal localization, structure or function of the heat shock proteins has been associated with many pathologies, including those involving heart disease. Heat shock proteins like HSP60 and HSP70 in particular have been identified as playing important roles in inflammation and immune reactions. Inflammation has been identified recently as an important pathological risk factor for heart disease. It is perhaps not surprising therefore, that heat shock protein family has been increasingly identified as an important intracellular pathway associated with inflammatory-mediated heart conditions including atherosclerosis. This paper reviews the evidence in support of a role for heat shock proteins in cardiovascular disease and the potential to target these proteins to alter the progression of atherosclerotic disease.

  14. Comparison of new bone formation, implant integration, and biocompatibility between RGD-hydroxyapatite and pure hydroxyapatite coating for cementless joint prostheses--an experimental study in rabbits.

    PubMed

    Bitschnau, Achim; Alt, Volker; Böhner, Felicitas; Heerich, Katharina Elisabeth; Margesin, Erika; Hartmann, Sonja; Sewing, Andreas; Meyer, Christof; Wenisch, Sabine; Schnettler, Reinhard

    2009-01-01

    This is the first work to report on additional Arginin-Glycin-Aspartat (RGD) coating on precoated hydroxyapatite (HA) surfaces regarding new bone formation, implant bone contact, and biocompatibility compared to pure HA coating and uncoated stainless K-wires. There were 39 rabbits in total with 6 animals for the RGD-HA and HA group for the 4 week time period and 9 animals for each of the 3 implant groups for the 12 week observation. A 2.0 K-wire either with RGD-HA or with pure HA coating or uncoated was placed into the intramedullary canal of the tibia. After 4 and 12 weeks, the tibiae were harvested and three different areas of the tibia were assessed for quantitative and qualitative histology for new bone formation, direct implant bone contact, and formation of multinucleated giant cells. Both RGD-HA and pure HA coating showed statistically higher new bone formation and implant bone contact after 12 weeks than the uncoated K-wire. There were no significant differences between the RGD-HA and the pure HA coating in new bone formation and direct implant bone contact after 4 and 12 weeks. The number of multinucleated giant did not differ significantly between the RGD-HA and HA group after both time points. Overall, no significant effects of an additional RGD coating on HA surfaces were detected in this model after 12 weeks.

  15. Early bone response to sandblasted, dual acid-etched and H2O2/HCl treated titanium implants: an experimental study in the rabbit.

    PubMed

    He, F M; Yang, G L; Li, Y N; Wang, X X; Zhao, S F

    2009-06-01

    The aim of this study was to evaluate the influence of a roughened H(2)O(2)/HCl heat-treated titanium surface on peri-implant bone formation at an early stage in vivo. 24 Ti(6)Al(4)V alloy implants were used; half were treated by sandblasted and dual acid-etched treatments (control group), while the others were treated by sandblasted, dual acid-etched and H(2)O(2)/HCl heat treatments (test group). The morphology and roughness were analyzed by field emission SEM and atomic force microscopy. The implants were inserted into the femora of 12 adult white rabbits. After 2 and 4 weeks, femora block specimens were prepared for histological and histomorphometric analysis. SEM micrographs showed that multilevel and different sized pits were formed on both surfaces. New bone formation was observed on both implant surfaces. Test implants demonstrated a greater mean percentage of bone-implant contact as compared with controls at 2 (46.84 vs. 41.81, p=0.000) and 4 weeks (49.43 vs. 44.87, p=0.006) of healing. It is concluded that the H(2)O(2)/HCl heat-treated rough titanium surface promoted enhanced bone apposition during the early stages of new bone formation around the implant.

  16. The effect of a cartilage bone marrow extract on experimentally induced osteoarthrosis in the knee joints of rabbits. A scanning electron microscopic study.

    PubMed

    Neumüller, J; Partsch, G; Adamiker, D; Eberl, R

    1981-03-01

    The development of osteoarthrosis following a partial meniscectomy on the knee cartilage of rabbits (Chinchilla hybrids) was monitored with a scanning electron microscope. Simultaneously, a study was made of the effect of the cartilage bone marrow extract Rumalon trademark on the development of the osteoarthrotic changes. Twelve days after the operation, osteoarthrotic changes were evident in the untreated operated joints. After 36 days the damage caused to the cartilage was already radical. The immobility of the operated joint also gave rise to obvious changes in the cartilage of the knee joints which had not undergone an operation. The irregular weight distribution due to the fixation of one joint was apparently enough to provoke degenerative processes on the other side. When the cartilage bone marrow extract Rumalon trademark was administered three times weekly (0.5 mg/kg body weight i.m.) a distinct retardation of the osteoarthrotic development in the early stages was observed. Where the changes had penetrated to the inner cartilage layers, no difference could be established compared to the untreated animals.

  17. Reconstruction of irradiated bone segmental defects with a biomaterial associating MBCP+(R), microstructured collagen membrane and total bone marrow grafting: an experimental study in rabbits.

    PubMed

    Jégoux, Franck; Goyenvalle, Eric; Cognet, Ronan; Malard, Olivier; Moreau, Francoise; Daculsi, Guy; Aguado, Eric

    2009-12-15

    The bone tissue engineering models used today are still a long way from any oncologic application as immediate postimplantation irradiation would decrease their osteoinductive potential. The aim of this study was to reconstruct a segmental critical size defect in a weight-bearing bone irradiated after implantation. Six white New Zealand rabbits were immediately implanted with a biomaterial associating resorbable collagen membrane EZ(R) filled and micro-macroporous biphasic calcium phosphate granules (MBCP+(R)). After a daily schedule of radiation delivery, and within 4 weeks, a total autologous bone marrow (BM) graft was injected percutaneously into the center of the implant. All the animals were sacrificed at 16 weeks. Successful osseous colonization was found to have bridged the entire length of the defects. Identical distribution of bone ingrowth and residual ceramics at the different levels of the implant suggests that the BM graft plays an osteoinductive role in the center of the defect. Periosteum-like formation was observed at the periphery, with the collagen membrane most likely playing a role. This model succeeded in bridging a large segmental defect in weight-bearing bone with immediate postimplantation fractionated radiation delivery. This has significant implications for the bone tissue engineering approach to patients with cancer-related bone defects.

  18. Does the method of expression of venous blood affect ischaemia/reperfusion damage in tourniquet use? An experimental study on rabbits.

    PubMed

    Iltar, Serkan; Kılınç, Cem Yalın; Alemdaroğlu, Kadir Bahadır; Ozcan, Selahattin; Aydoğan, Nevres Hürriyet; Sürer, Hatice; Kılınç, Aytün Şadan

    2013-11-01

    The aim of this study was to compare the ischaemia and reperfusion phases of two tourniquet application models (Group 1: expressing the blood by a sterile rubber bandage and Group 2: elevation of the limb for several minutes) using an analysis of ischaemia/reperfusion parameters and blood pH. Sixteen New Zealand rabbits were used. Muscle samples were extracted from the triceps surae; at phase A (baseline: just before tourniquet application), phase B (ischaemia: 3h after tourniquet inflation) and phase C (2h after tourniquet deflation). Nitrite, nitrate, reduced glutathione, myeloperoxidase, malondyaldehyde were measured in the samples. Blood pH was also measured at each phase. Group 2 had significantly decreased nitrite (p=0.007) and nitrate (p=0.01) levels compared to Group 1 while passing from phase A to phase B. The pH decrease through the phases was significant within Group 1 (p=0.006) and was not significant within Group 2 (p=0.052). Lower levels of NO metabolites nitrate and nitrite, result from tourniquet use with incomplete venous blood expression by elevation. Also, with this technique severe acidosis is less likely to occur than when a tourniquet is used with expression of the venous blood by rubber bandage. These findings may help in the decision of which tourniquet technique is to be used for potentially long operations which may exceed 2h.

  19. Pre-treatment with simvastatin prevents the induction of diet-induced atherosclerosis in a rabbit model

    PubMed Central

    Oikonomidis, Nikolaos; Kavantzas, Nikolaos; Korou, Laskarina-Maria; Konstantopoulos, Panagiotis; Pergialiotis, Vasilios; Misiakos, Evangelos; Rizos, Ioannis; Verikokos, Christos; Perrea, Despina N.

    2016-01-01

    The aim of the present study was to investigate the potential antiatherosclerotic activities of simvastatin in rabbits. Twenty-two, male, New Zealand rabbits were divided into the following groups: Control group (group C); cholesterol group (group A), in which the rabbits were fed a commercial rabbit chow supplemented with 0.5% w/w cholesterol for 8 weeks and then fed with normal chow for an additional 8 weeks; and a treatment group (group B), in which the rabbits initially received standard commercial rabbit chow along with being administered simvastatin for 8 weeks, following which they consumed a high-cholesterol diet for a further 8 weeks. The rabbits pre-treated with simvastatin presented significantly lower serum cholesterol and low-density lipoprotein cholesterol levels when compared with the non simvastatin-treated cholesterol-fed animals. Furthermore, none of the rabbits in the simvastatin group presented with atherosclerotic lesions in the aorta. Thus, simvastatin was demonstrated to exhibit preventive properties against the formation of atherosclerosis in the atherosclerosis model in the current study, predominantly via its hypolipidemic activity. PMID:28101339

  20. Anti-Atherogenic Properties of Allium ursinum Liophylisate: Impact on Lipoprotein Homeostasis and Cardiac Biomarkers in Hypercholesterolemic Rabbits.

    PubMed

    Bombicz, Mariann; Priksz, Daniel; Varga, Balazs; Gesztelyi, Rudolf; Kertesz, Attila; Lengyel, Peter; Balogh, Peter; Csupor, Dezso; Hohmann, Judit; Bhattoa, Harjit Pal; Haines, David D; Juhasz, Bela

    2016-08-10

    The present investigation evaluates the capacity of Allium ursinum (wild garlic) leaf lyophilisate (WGLL; alliin content: 0.261%) to mitigate cardiovascular damage in hypercholesterolemic rabbits. New Zealand rabbits were divided into three groups: (i) cholesterol-free rabbit chow (control); (ii) rabbit chow containing 2% cholesterol (hypercholesterolemic, HC); (iii) rabbit chow containing 2% cholesterol + 2% WGLL (hypercholesterolemic treated, HCT); for eight weeks. At the zero- and eight-week time points, echocardiographic measurements were made, along with the determination of basic serum parameters. Following the treatment period, after ischemia-reperfusion injury, hemodynamic parameters were measured using an isolated working heart model. Western blot analyses of heart tissue followed for evaluating protein expression and histochemical study for the atheroma status determination. WGLL treatment mediated increases in fractional shortening; right ventricular function; peak systolic velocity; tricuspidal annular systolic velocity in live animals; along with improved aortic and coronary flow. Western blot analysis revealed WGLL-associated increases in HO-1 protein and decreases in SOD-1 protein production. WGLL-associated decreases were observed in aortic atherosclerotic plaque coverage, plasma ApoB and the activity of LDH and CK (creatine kinase) in plasma. Plasma LDL was also significantly reduced. The results clearly demonstrate that WGLL has complex cardioprotective effects, suggesting future strategies for its use in prevention and therapy for atherosclerotic disorders.

  1. Promotion of atherosclerosis in high cholesterol diet-fed rabbits by immunization with the P277 peptide.

    PubMed

    Xiong, Qiyan; Feng, Jiao; Zhang, Yu; Sun, Yunxiao; Lu, Yong; Li, Taiming; Zhang, Xiaohong; Cao, Rongyue; Jin, Liang; Wu, Jie

    2016-02-01

    Previous evidence has proved the ability of immunization with heat shock protein (HSP) 60/65 to induce atherosclerosis. P277, a 24-residue peptide of human HSP60, is a promising peptide vaccine against autoimmune diabetes. But as a fragment of HSP60, its potential ability of promoting atherosclerosis has never been investigated yet. In the present study, the rabbits fed with normal standard diet or high cholesterol diet were immunized with P277 or PBS emulsified in incomplete Freund's adjuvant 4 times at 4-week intervals. Atherosclerotic lesions of the rabbits receiving P277 treatment and fed with high cholesterol diet increased significantly compared with those of the rabbits receiving PBS treatment and the same diet. However, no obvious lesions were found in the two groups of rabbits fed with the normal standard diet. Significant expression of P277 was detected in the high cholesterol diet-induced atherosclerotic lesions and heat-stressed endothelial cells. Surface exposure of P277 was also observed in the stressed cells. In the subsequent assay of endothelial cells in vitro, the purified anti-P277 antibodies mediated a noticeable cytotoxicity to the stressed cells with the participation of complement. In conclusion, subcutaneous immunization with P277 emulsified in IFA can aggravate the atherosclerosis in high cholesterol diet-fed rabbits. Surface expression of P277 was observed on stressed endothelial cells, and were suggested to mediate the autoimmune attack and promote the disease.

  2. Anti-Atherogenic Properties of Allium ursinum Liophylisate: Impact on Lipoprotein Homeostasis and Cardiac Biomarkers in Hypercholesterolemic Rabbits

    PubMed Central

    Bombicz, Mariann; Priksz, Daniel; Varga, Balazs; Gesztelyi, Rudolf; Kertesz, Attila; Lengyel, Peter; Balogh, Peter; Csupor, Dezso; Hohmann, Judit; Bhattoa, Harjit Pal; Haines, David D.; Juhasz, Bela

    2016-01-01

    The present investigation evaluates the capacity of Allium ursinum (wild garlic) leaf lyophilisate (WGLL; alliin content: 0.261%) to mitigate cardiovascular damage in hypercholesterolemic rabbits. New Zealand rabbits were divided into three groups: (i) cholesterol-free rabbit chow (control); (ii) rabbit chow containing 2% cholesterol (hypercholesterolemic, HC); (iii) rabbit chow containing 2% cholesterol + 2% WGLL (hypercholesterolemic treated, HCT); for eight weeks. At the zero- and eight-week time points, echocardiographic measurements were made, along with the determination of basic serum parameters. Following the treatment period, after ischemia-reperfusion injury, hemodynamic parameters were measured using an isolated working heart model. Western blot analyses of heart tissue followed for evaluating protein expression and histochemical study for the atheroma status determination. WGLL treatment mediated increases in fractional shortening; right ventricular function; peak systolic velocity; tricuspidal annular systolic velocity in live animals; along with improved aortic and coronary flow. Western blot analysis revealed WGLL-associated increases in HO-1 protein and decreases in SOD-1 protein production. WGLL-associated decreases were observed in aortic atherosclerotic plaque coverage, plasma ApoB and the activity of LDH and CK (creatine kinase) in plasma. Plasma LDL was also significantly reduced. The results clearly demonstrate that WGLL has complex cardioprotective effects, suggesting future strategies for its use in prevention and therapy for atherosclerotic disorders. PMID:27517918

  3. Coccidian and nematode infections influence prevalence of antibody to myxoma and rabbit hemorrhagic disease viruses in European rabbits.

    PubMed

    Bertó-Moran, Alejandro; Pacios, Isabel; Serrano, Emmanuel; Moreno, Sacramento; Rouco, Carlos

    2013-01-01

    The interaction among several parasites in European rabbits (Oryctolagus cuniculus) is crucial to host fitness and to the epidemiology of myxomatosis and rabbit hemorrhagic disease. These diseases have caused significant reductions in rabbit populations on the Iberian Peninsula. Most studies have focused on the epidemiology and pathogenesis of these viruses individually, and little is known about interactions between these viruses and other parasites. Taking advantage of an experimental restocking program in Spain, the effects of coccidian and nematode infections on the probability of having detectable antibody to myxoma and rabbit hemorrhagic disease viruses were tested in European wild rabbits. For 14 mo, we monitored rabbit abundance and parasite loads (coccidia and nematodes) in three reintroduced rabbit populations. While coccidian and nematode loads explained seasonal antibody prevalences to myxoma virus, the pattern was less clear for rabbit hemorrhagic disease. Contrary to expectations, prevalence of antibody to myxoma virus was inversely proportional to coccidian load, while nematode load seemed to play a minor role. These results have implications for viral disease epidemiology and for disease management intended to increase rabbit populations in areas where they are important for ecosystem conservation.

  4. Detection of a Molecular Biomarker for Zygomycetes by Quantitative PCR Assays of Plasma, Bronchoalveolar Lavage, and Lung Tissue in a Rabbit Model of Experimental Pulmonary Zygomycosis▿

    PubMed Central

    Kasai, Miki; Harrington, Susan M.; Francesconi, Andrea; Petraitis, Vidmantas; Petraitiene, Ruta; Beveridge, Mara G.; Knudsen, Tena; Milanovich, Jeffery; Cotton, Margaret P.; Hughes, Johanna; Schaufele, Robert L.; Sein, Tin; Bacher, John; Murray, Patrick R.; Kontoyiannis, Dimitrios P.; Walsh, Thomas J.

    2008-01-01

    We developed two real-time quantitative PCR (qPCR) assays, targeting the 28S rRNA gene, for the diagnosis of zygomycosis caused by the most common, clinically significant Zygomycetes. The amplicons of the first qPCR assay (qPCR-1) from Rhizopus, Mucor, and Rhizomucor species were distinguished through melt curve analysis. The second qPCR assay (qPCR-2) detected Cunninghamella species using a different primer/probe set. For both assays, the analytic sensitivity for the detection of hyphal elements from germinating sporangiospores in bronchoalveolar lavage (BAL) fluid and lung tissue homogenates from rabbits was 1 to 10 sporangiospores/ml. Four unique and clinically applicable models of invasive pulmonary zygomycosis served as surrogates of human infections, facilitating the validation of these assays for potential diagnostic utility. For qPCR-1, 5 of 98 infarcted lung specimens were positive by qPCR and negative by quantitative culture (qCx). None were qCx positive only. Among 23 BAL fluid samples, all were positive by qPCR, while 22 were positive by qCx. qPCR-1 detected Rhizopus and Mucor DNA in 20 (39%) of 51 serial plasma samples as early as day 1 postinoculation. Similar properties were observed for qPCR-2, which showed greater sensitivity than qCx for BAL fluid (100% versus 67%; P = 0.04; n = 15). The assay detected Cunninghamella DNA in 18 (58%) of 31 serial plasma samples as early as day 1 postinoculation. These qPCR assays are sensitive and specific for the detection of Rhizopus, Mucor, Rhizomucor, and Cunninghamella species and can be used for the study and detection of infections caused by these life-threatening pathogens. PMID:18845827

  5. Genotoxicity effect, antioxidant and biomechanical correlation: experimental study of agarose-chitosan bone graft substitute in New Zealand white rabbit model.

    PubMed

    Jebahi, Samira; Ben Saleh, Ghada; Saoudi, Mongi; Besaleh, Salma; Oudadesse, Hassane; Mhadbi, Moufida; Rebai, Tarek; Keskes, Hassib; El Feki, Abdelfattah

    2014-08-01

    Bone loss associated with skeletal trauma or metabolic diseases often requires bone grafting. In such situations, a biomaterial is necessary for migrated cells to produce new tissue. In this study, agarose-chitosan was implanted in the femoral condyle of New Zealand White rabbits that were divided into three groups: Group I was used as control; Groups II and III were used as implanted tissue with agarose-chitosan and presenting empty defects, respectively. This study evaluated the agarose-chitosan biocompatibility by determining the in vivo genotoxicity, oxidative stress balance that correlated with the hardness mechanical property. Moreover, the histopathological and quantitative elements analyzed by using inductively coupled plasma optical emission spectrometry were determined. After 30 days of implantation, the in vivo analysis of genotoxicity showed that agarose-chitosan did not induce chromosome aberration or micronucleus damage. A significant decrease in thiobarbituric and acid-reactive substance was observed after agarose-chitosan implantation in the bone tissue. Superoxide dismutase, catalase and glutathione peroxidase were significantly enhanced in agarose-chitosan-treated group compared with that of control group. A negative correlation coefficient of the mechanical property with malonyldialdehyde level was detected (R = -0.998). The histological study exhibited a significantly increased angiogenesis and newly formed tissue. No presence of inflammatory process, necrotic or fibrous tissue was detected. Major and trace elements such as Ca, P, Zn, Mg and Fe were increased significantly in the newly formed bone. These findings show that agarose-chitosan biomaterial implantation might be effective for treating trauma and bone regeneration.

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

    PubMed

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

    2016-09-01

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

  7. SERUM SICKNESS IN RABBITS

    PubMed Central

    Fleisher, Mover S.; Jones, Lloyd

    1931-01-01

    1. The injection of a single large dose of normal horse serum into rabbits results in the appearance 3 to 8 days later of erythematous and edematous reactions on the ears in 68.9 per cent of the animals. 2. The injections may be given by any of several routes and reactions appear when the site of injection is definitely distant from the ears. 3. Injections of various antisera into rabbits cause the appearance of similar reactions. 4. These reactions can be considered as manifestations of serum sickness in rabbits. PMID:19869943

  8. Rabbit orthopedic surgery.

    PubMed

    Rich, Gregory A

    2002-01-01

    Orthopedic surgery in rabbits poses several unique parameters for the veterinary surgeon. It is imperative for the veterinarian to be knowledgeable about the anatomic features of the surgical repair site and to become familiar with a rabbit's pain and discomfort often associated with orthopedic injuries. Handling the perioperative and postoperative pain and potential GI disturbances are crucial for a successful outcome of the surgical case. This article is designed to help the veterinary surgeon prepare for the orthopedic surgical procedure and the peripheral physiologic needs of the rabbit from presentation through recovery.

  9. Targeting macrophage Histone deacetylase 3 stabilizes atherosclerotic lesions

    PubMed Central

    Hoeksema, Marten A; Gijbels, Marion JJ; Van den Bossche, Jan; van der Velden, Saskia; Sijm, Ayestha; Neele, Annette E; Seijkens, Tom; Stöger, J Lauran; Meiler, Svenja; Boshuizen, Marieke CS; Dallinga-Thie, Geesje M; Levels, Johannes HM; Boon, Louis; Mullican, Shannon E; Spann, Nathanael J; Cleutjens, Jack P; Glass, Chris K; Lazar, Mitchell A; de Vries, Carlie JM; Biessen, Erik AL; Daemen, Mat JAP; Lutgens, Esther; de Winther, Menno PJ

    2014-01-01

    Macrophages are key immune cells found in atherosclerotic plaques and critically shape atherosclerotic disease development. Targeting the functional repertoire of macrophages may hold novel approaches for future atherosclerosis management. Here, we describe a previously unrecognized role of the epigenomic enzyme Histone deacetylase 3 (Hdac3) in regulating the atherosclerotic phenotype of macrophages. Using conditional knockout mice, we found that myeloid Hdac3 deficiency promotes collagen deposition in atherosclerotic lesions and thus induces a stable plaque phenotype. Also, macrophages presented a switch to anti-inflammatory wound healing characteristics and showed improved lipid handling. The pro-fibrotic phenotype was directly linked to epigenetic regulation of the Tgfb1 locus upon Hdac3 deletion, driving smooth muscle cells to increased collagen production. Moreover, in humans, HDAC3 was the sole Hdac upregulated in ruptured atherosclerotic lesions, Hdac3 associated with inflammatory macrophages, and HDAC3 expression inversely correlated with pro-fibrotic TGFB1 expression. Collectively, we show that targeting the macrophage epigenome can improve atherosclerosis outcome and we identify Hdac3 as a potential novel therapeutic target in cardiovascular disease. PMID:25007801

  10. Ultrafast laser ablation for targeted atherosclerotic plaque removal

    NASA Astrophysics Data System (ADS)

    Lanvin, Thomas; Conkey, Donald B.; Descloux, Laurent; Frobert, Aurelien; Valentin, Jeremy; Goy, Jean-Jacques; Cook, Stéphane; Giraud, Marie-Noelle; Psaltis, Demetri

    2015-07-01

    Coronary artery disease, the main cause of heart disease, develops as immune cells and lipids accumulate into plaques within the coronary arterial wall. As a plaque grows, the tissue layer (fibrous cap) separating it from the blood flow becomes thinner and increasingly susceptible to rupturing and causing a potentially lethal thrombosis. The stabilization and/or treatment of atherosclerotic plaque is required to prevent rupturing and remains an unsolved medical problem. Here we show for the first time targeted, subsurface ablation of atherosclerotic plaque using ultrafast laser pulses. Excised atherosclerotic mouse aortas were ablated with ultrafast near-infrared (NIR) laser pulses. The physical damage was characterized with histological sections of the ablated atherosclerotic arteries from six different mice. The ultrafast ablation system was integrated with optical coherence tomography (OCT) imaging for plaque-specific targeting and monitoring of the resulting ablation volume. We find that ultrafast ablation of plaque just below the surface is possible without causing damage to the fibrous cap, which indicates the potential use of ultrafast ablation for subsurface atherosclerotic plaque removal. We further demonstrate ex vivo subsurface ablation of a plaque volume through a catheter device with the high-energy ultrafast pulse delivered via hollow-core photonic crystal fiber.

  11. High shear stress induces atherosclerotic vulnerable plaque formation through angiogenesis

    PubMed Central

    Wang, Yi; Qiu, Juhui; Luo, Shisui; Xie, Xiang; Zheng, Yiming; Zhang, Kang; Ye, Zhiyi; Liu, Wanqian; Gregersen, Hans; Wang, Guixue

    2016-01-01

    Rupture of atherosclerotic plaques causing thrombosis is the main cause of acute coronary syndrome and ischemic strokes. Inhibition of thrombosis is one of the important tasks developing biomedical materials such as intravascular stents and vascular grafts. Shear stress (SS) influences the formation and development of atherosclerosis. The current review focuses on the vulnerable plaques observed in the high shear stress (HSS) regions, which localizes at the proximal region of the plaque intruding into the lumen. The vascular outward remodelling occurs in the HSS region for vascular compensation and that angiogenesis is a critical factor for HSS which induces atherosclerotic vulnerable plaque formation. These results greatly challenge the established belief that low shear stress is important for expansive remodelling, which provides a new perspective for preventing the transition of stable plaques to high-risk atherosclerotic lesions. PMID:27482467

  12. Besnoitia oryctofelisi n. sp. (Protozoa: Apicomplexa) from domestic rabbits.

    PubMed

    Dubey, J P; Sreekumar, C; Lindsay, D S; Hill, D; Rosenthal, B M; Venturini, L; Venturini, M C; Greiner, E C

    2003-06-01

    A species of Besnoitia from naturally infected rabbits from Argentina was propagated experimentally in mice, gerbils, rabbits, cats, and cell cultures. Cats fed tissue cysts from rabbits shed oocysts with a prepatent period of nine to 13 days. Sporulated oocysts were infective to gerbils, rabbits, outbred Swiss Webster and interferon gamma gene knockout mice. Bradyzoites were infective orally to gerbils and cats. Tachyzoites were successfully cultivated and maintained in vitro in bovine monocytes and African green monkey kidney cells. Schizonts were seen in the lamina propria of the small intestine of cats fed tissue cysts; the largest ones measured 52 x 45 microm. Schizonts were also present in mesenteric lymph nodes, livers, and other extra-intestinal organs of cats fed tissue cysts. Oocysts were 10-14 x 10-13 microm in size. This rabbit-derived species of Besnoitia resembled B. darlingi of the North American opossum, Didelphis virginiana with an opossum-cat cycle, but it was not transmissible to D. virginiana, and B. darlingi of opossums was not transmissible to rabbits. Based on biological, serological, antigenic, and molecular differences between the rabbit and the opossum Besnoitia, a new name, B. oryctofelisi is proposed for the parasite from domestic rabbits from Argentina.

  13. Localization to atherosclerotic plaque and biodistribution of biochemically derivatized superparamagnetic iron oxide nanoparticles (SPIONs) contrast particles for magnetic resonance imaging (MRI).

    PubMed

    Smith, Bryan R; Heverhagen, Johannes; Knopp, Michael; Schmalbrock, Petra; Shapiro, John; Shiomi, Masashi; Moldovan, Nicanor I; Ferrari, Mauro; Lee, Stephen C

    2007-10-01

    Annexin V recognizes apoptotic cells by specific molecular interaction with phosphatidyl serine, a lipid that is normally sequestered in the inner leaflet of the cell membrane, but is translocated to the outer leaflet in apoptotic cells, such as foam cells of atherosclerotic plaque. Annexin V could potentially deliver carried materials (such as superparamagnetic contrast agents for magnetic resonance imaging) to sites containing apoptotic cells, such as high grade atherosclerotic lesions, so we administered biochemically-derivatized (annexin V) superparmagnetic iron oxide particles (SPIONs) parenterally to two related rabbit models of human atherosclerosis. We observe development of negative magnetic resonance imaging (MRI) contrast in atheromatous lesions and but not in healthy artery. Vascular targeting by annexin V SPIONs is atheroma-specific (i.e., does not occur in healthy control rabbits) and requires active annexin V decorating the SPION surface. Targeted SPIONs produce negative contrast at doses that are 2,000-fold lower than reported for non-specific atheroma uptake of untargeted superparamagnetic nanoparticles in plaque in the same animal model. Occlusive and mural plaques are differentiable. While most of the dose accumulates in liver, spleen, kidneys and bladder, annexin V SPIONs also partition rapidly and deeply into early apoptotic foamy macrophages in plaque. Contrast in plaque decays within 2 months, allowing MRI images to be replicated with a subsequent, identical dose of annexin V SPIONs. Thus, biologically targeted superparamagnetic contrast agents can contribute to non-invasive evaluation of cardiovascular lesions by simultaneously extracting morphological and biochemical data from them.

  14. Spontaneous fatal Human herpesvirus 1 encephalitis in two domestic rabbits (Oryctolagus cuniculus).

    PubMed

    de Matos, Ricardo; Russell, Duncan; Van Alstine, William; Miller, Andrew

    2014-09-01

    Despite the particular susceptibility of the rabbit to experimental infection with Human herpesvirus 1 (HHV-1) and the high seroprevalence of HHV-1 in human beings, reports of natural infection in pet rabbits are rare. The current report describes 2 cases of HHV encephalitis in pet rabbits in North America. Antemortem clinical signs included seizures, ptyalism, and muscle tremors. Results of complete blood cell count and plasma biochemistry panel were unremarkable except for a mild leukocytosis in both cases. Both rabbits died after a short period of hospitalization. Rabbit 1 presented mild optic chiasm hemorrhage on gross examination, while rabbit 2 had no gross lesions. Histologic findings for both cases included lymphocytic and/or lymphoplasmacytic encephalitis with necrosis and the presence of intranuclear inclusion bodies in neurons and glial cells. Polymerase chain reaction (PCR) analysis of affected brain tissue using primers specific for Human herpesvirus 1 and 2 confirmed diagnosis of HHV encephalitis for rabbit 1. Immunohistochemical staining (poly- and monoclonal) and PCR analysis using primers specific to HHV-1 confirmed the diagnosis of HHV-1 encephalitis for rabbit 2. The owner of rabbit 2 was suspected to be the source of infection due to close contact during an episode of herpes labialis. Given the high susceptibility of rabbits to experimental HHV-1, high seroprevalence of HHV-1 in human beings, and severity of clinical disease in this species, clinician awareness and client education is important for disease prevention. Human herpesvirus 1 encephalitis should be considered as a differential diagnosis for rabbits with neurologic disease.

  15. Antiatherosclerotic and Cardioprotective Potential of Acacia senegal Seeds in Diet-Induced Atherosclerosis in Rabbits

    PubMed Central

    Ram, Heera; Jatwa, Rameshwar; Purohit, Ashok

    2014-01-01

    Acacia senegal L. (Fabaceae) seeds are essential ingredient of “Pachkutta,” a specific Rajasthani traditional food. The present study explored antiatherosclerotic and cardioprotective potential of Acacia senegal seed extract, if any, in hypercholesterolemic diet-induced atherosclerosis in rabbits. Atherosclerosis in rabbits was induced by feeding normal diet supplemented with oral administration of cholesterol (500 mg/kg body weight/day mixed with coconut oil) for 15 days. Circulating total cholesterol (TC), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), triglycerides, and VLDL-cholesterol (VLDL-C) levels; atherogenic index (AI); cardiac lipid peroxidation (LPO); planimetric studies of aortal wall; and histopathological studies of heart, aorta, kidney, and liver were performed. Apart from reduced atherosclerotic plaques in aorta (6.34 ± 0.72) and increased lumen volume (51.65 ± 3.66), administration with ethanolic extract of Acacia senegal seeds (500 mg/kg/day, p.o.) for 45 days to atherosclerotic rabbits significantly lowered serum TC, LDL-C, triglyceride, and VLDL-C levels and atherogenic index as compared to control. Atherogenic diet-induced cardiac LPO and histopathological abnormalities in aorta wall, heart, kidney, and liver were reverted to normalcy by Acacia senegal seed extract administration. The findings of the present study reveal that Acacia senegal seed extract ameliorated diet-induced atherosclerosis and could be considered as lead in the development of novel therapeutics. PMID:25544897

  16. Effect of aqueous extract of Vernonia amygdalina on atherosclerosis in rabbits

    PubMed Central

    Abdulmalik, Omotola; Oladapo, Olulola Olutoyin; Bolaji, Modupeola Oluwabunmi

    2016-01-01

    BACKGROUND Extracts of Vernonia amygdalina (V. amygdalina) have been shown to affect the serum lipid profile of some laboratory animals in previous studies. Its impact on serum lipid profile and the histological changes in atherosclerosis has not been studied. Our aim was to determine the effects of V. amygdalina on atherosclerotic lesions induced in rabbits on high-cholesterol diet. METHODS 18 male rabbits were randomly divided into three groups of control, atherogenic diet, and atherogenic diet + 200 mg/kg of V. amygdalina. The rabbits were fed a normal diet (control group) or a diet supplemented by 0.5% cholesterol and 1% methionine (second and third groups, respectively) for 12 weeks. The fasting sera of all animals were collected at baseline and at the end of the 12 weeks, to determine the levels of lipid profile and the aortas underwent pathomorphological examination. RESULTS The two groups on the atherogenic diet had significantly increased serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) compared to the control group. The serum triglyceride (TG) was not statistically different in all three groups. High-density lipoprotein cholesterol (HDL-C) was significantly increased in the V. amygdalina group, compared to the control group but there was no statistically significant difference between the two groups on atherogenic diet. The two groups of rabbits that were on high-cholesterol diet (atherogenic diet group, as well as the atherogenic diet + 200 mg/kg of V. amygdalina) developed histological evidence of atherosclerosis. However, there was no histological difference between the lesions observed in these two groups. CONCLUSION The use of 200 mg/kg of aqueous extract of V. amygdalina in rabbits did not appear to exert a significant effect on the serum lipid profile. It also did not appear to have any beneficial effect on the development of atherosclerotic lesions. PMID:27114735

  17. Fluorescence lifetime imaging microscopy for the characterization of atherosclerotic plaques

    NASA Astrophysics Data System (ADS)

    Phipps, Jennifer; Sun, Yinghua; Saroufeem, Ramez; Hatami, Nisa; Marcu, Laura

    2009-02-01

    Atherosclerotic plaque composition has been associated with plaque instability and rupture. This study investigates the use of fluorescence lifetime imaging microscopy (FLIM) for mapping plaque composition and assessing features of vulnerability. Measurements were conducted in atherosclerotic human aortic samples using an endoscopic FLIM system (spatial resolution of 35 µm temporal resolution 200 ps) developed in our lab which allows mapping in one measurement the composition within a volume of 4 mm diameter x 250 µm depth. Each pixel in the image represents a corresponding fluorescence lifetime value; images are formed through a flexible 0.6 mm side-viewing imaging bundle which allows for further intravascular applications. Based on previously recorded spectra of human atherosclerotic plaque, fluorescence emission was collected through two filters: f1: 377/50 and f2: 460/60 (center wavelength/bandwidth), which together provides the greatest discrimination between intrinsic fluorophores related to plaque vulnerability. We have imaged nine aortas and lifetime images were retrieved using a Laguerre expansion deconvolution technique and correlated with histopathology. Early results demonstrate discrimination using fluorescence lifetime between early, lipid-rich, and collagen-rich lesions which are consistent with previously reported time-resolved atherosclerotic plaque measurements.

  18. Antiinflammatory actions of inorganic nitrate stabilize the atherosclerotic plaque

    PubMed Central

    Khambata, Rayomand S.; Ghosh, Suborno M.; Rathod, Krishnaraj S.; Thevathasan, Tharssana; Filomena, Federica; Xiao, Qingzhong; Ahluwalia, Amrita

    2017-01-01

    Reduced bioavailable nitric oxide (NO) plays a key role in the enhanced leukocyte recruitment reflective of systemic inflammation thought to precede and underlie atherosclerotic plaque formation and instability. Recent evidence demonstrates that inorganic nitrate (NO3−) through sequential chemical reduction in vivo provides a source of NO that exerts beneficial effects upon the cardiovascular system, including reductions in inflammatory responses. We tested whether the antiinflammatory effects of inorganic nitrate might prove useful in ameliorating atherosclerotic disease in Apolipoprotein (Apo)E knockout (KO) mice. We show that dietary nitrate treatment, although having no effect upon total plaque area, caused a reduction in macrophage accumulation and an elevation in smooth muscle accumulation within atherosclerotic plaques of ApoE KO mice, suggesting plaque stabilization. We also show that in nitrate-fed mice there is reduced systemic leukocyte rolling and adherence, circulating neutrophil numbers, neutrophil CD11b expression, and myeloperoxidase activity compared with wild-type littermates. Moreover, we show in both the ApoE KO mice and using an acute model of inflammation that this effect upon neutrophils results in consequent reductions in inflammatory monocyte expression that is associated with elevations of the antiinflammatory cytokine interleukin (IL)-10. In summary, we demonstrate that inorganic nitrate suppresses acute and chronic inflammation by targeting neutrophil recruitment and that this effect, at least in part, results in consequent reductions in the inflammatory status of atheromatous plaque, and suggest that this effect may have clinical utility in the prophylaxis of inflammatory atherosclerotic disease. PMID:28057862

  19. Effect of a hypercholesterolemia as a starting factor on spinal degeneration in rabbits and role of Vitamin E (α-tocopherol)

    PubMed Central

    Sasani, Mehdi; Aydın, Ahmet Levent; Aytan, Nurgul; Yapicier, Ozlem; Oktenoglu, Tunc; Ozer, Nesrin Kartal; Ozer, Ali Fahir

    2016-01-01

    Background: To identify the role of the hypercholesterolemia as a starting factor in discovertebral degeneration that ultimately causes lower back pain, and investigate the role of Vitamin E in this process. Methods: The rabbits (n = 32) were divided into two broad experimental groups: A control group, and a hypercholesterolemia group, namely cholesterol, and cholesterol plus Vitamin E groups and they were fed sequentially for 4 or 8 weeks. Serum cholesterol and Vitamin E (α-tocopherol) levels were determined; vascular tissue was prepared for histopathological analyses and vertebra was decalcified for the study. Results: Cholesterol diet group resulted approximately 44-fold of increase plasma cholesterol levels over the 4-week control values. Additional supplementation with Vitamin E group induced a plasma cholesterol level increase of only 37-fold as compared to the control group. In the cholesterol groups, light microscope examination revealed atherosclerotic plaque in major arteries. However, in the cholesterol plus Vitamin E treatment groups, no lipid accumulation or foam cell formation was visible in the abdominal aorta and vertebral segmental artery. In histopathological examination, we found degenerative changes in the discovertebral unit in cholesterol treated groups. Conclusion: Hypercholesterolemia causes fat accumulation in the disc endplate and vertebral body that causes blood supply disturbances which might be a starting factor of discovertebral degeneration. This event was not reversed by the elimination of cholesterol from the diet. Vitamin E supplementation was not effective in reducing fat accumulation in vertebral bone marrow. As a result, we conclude that degeneration of the discovertebral unit is not related to atherosclerotic changes in the major blood vessels. PMID:27127701

  20. Prolonged oral cyanide effects on feed intake, growth rate and blood parameters in rabbits.

    PubMed

    Avais, Muhammad; Khan, Muhammad Sarwar; Khan, Muhammad Arif; Ashraf, Kamran; Khan, Jawaria Ali; Hameed, Sajid

    2014-07-01

    Twelve adult rabbits bred locally were divided into two equal groups of 6; experimental and control groups. Rabbits in the experimental group were orally dosed with KCN at 3mg/kg body weight for 40 consecutive days. Members in control group were given placebo (distilled water) for the same period. Animals in both groups were offered feed at 90gm/kg/day while ample drinking water was available ad lib. Feed consumption and body weight of rabbits in both the groups were recorded. Blood samples were also drawn to determine various hematological parameters. Statistical analysis revealed a non-significant difference of total and daily feed intakes in rabbits of experimental and control groups. Whereas the feed efficiency of rabbits in the experimental group were significantly reduced (P<0.05) compared to controls. Likewise a significant decrease in body weight gain of rabbits in experimental group (P<0.05) was observed. A non-significant difference (P>0.05) was observed in leukocyte count, differential leukocyte count and platelets of rabbits in both the groups. Erythrocyte count, hemoglobin concentration, packed cell volume and mean corpuscular hemoglobin were significantly decreased in treated rabbits. It was concluded that chronic cyanide intake had a deleterious effect on feed efficiency, growth rate and blood components of rabbits.

  1. Assessment of a Novel Vaccine Against Rabbit Hemorrhagic Disease Virus in Young Rabbits.

    PubMed

    Pacho, Sonsoles; Dahdouh, Elias; Merino, Javier; Suárez, Monica

    2016-12-01

    Rabbit hemorrhagic disease virus (RHDVb) is the new variant of the classical RHDV, a virulent pathogen responsible for an acute disease in young rabbits. The virus invades internal organs, especially the liver, spleen, kidneys, and gut; prevents coagulation; and causes liver necrosis. This eventually leads to quick death of the animal because of hemorrhage. In this study, we evaluated the effects of a new vaccine against RHDVb in rabbits at a young age, after experimental infection using four different viral isolates. Our findings show that the vaccine had a protective effect with survival rates reaching 80-100% against the different isolates. These results suggest that this vaccine, when applied to young animals, is an effective tool to protect against the disease caused by RHDVb in rabbitries.

  2. The Cutaneous Rabbit Revisited

    ERIC Educational Resources Information Center

    Flach, Rudiger; Haggard, Patrick

    2006-01-01

    In the cutaneous rabbit effect (CRE), a tactile event (so-called attractee tap) is mislocalized toward an adjacent attractor tap. The effect depends on the time interval between the taps. The authors delivered sequences of taps to the forearm and asked participants to report the location of one of the taps. The authors replicated the original CRE…

  3. Autoantibody Production in Rabbits

    PubMed Central

    Asherson, G. L.; Dumonde, D. C.

    1963-01-01

    The sera of rabbits injected with rat liver, kidney, heart, muscle, spleen and brain in Freund's complete adjuvant fixed complement with rabbit tissue. This complement-fixing activity was attributed to autoantibodies which were able to fix complement in vitro with the tissue of the rabbit in which they occurred. Absorption, gel diffusion and antibody and antigen titrations indicated that some of the anti-liver, anti-kidney, anti-heart, anti-muscle and anti-brain sera contained organ-specific autoantibody. The sera also contained autoantibody reacting with widely distributed antigen(s), which was relatively labile at 65°. The anti-kidney and anti-brain sera reacted with distinct antigens which were extracted from rabbit kidney and brain with a mixture of chloroform and methanol. The natural autoantibody of Kidd and Friedewald was usually labile at 65° and behaved like a macroglobulin on sucrose gradient centrifugation. Sera taken 1 week after immunization with rat tissue contained heat-labile macroglobulin antibody. However, sera taken 1 month after immunization also contained small molecular weight antibody which was stable at 65°. PMID:13965166

  4. Effect of methanolic extract of Piper sarmentosum leaves on neointimal foam cell infiltration in rabbits fed with high cholesterol diet

    PubMed Central

    Amran, Adel A.; Zakaria, Zaiton; Othman, Faizah; Das, Srijit; Al-Mekhlafi, Hesham M.; Raj, Santhana; Nordin, Nor-Anita MM

    2012-01-01

    Previous research has shown the beneficial effects of aqueous extract of Piper sarmentosum (P.s) on atherosclerosis. The first stage in atherosclerosis is the formation of foam cell. The aim of this study was to investigate the effect of the methanol extract of P.s on fatty streaks by calculating neointimal foam cell infiltration in rabbits fed with high cholesterol diet. Thirty six male New Zealand white rabbits were divided equally into six groups: (i) C: control group fed normal rabbit chow; (ii) CH: cholesterol diet (1 % cholesterol); (iii) PM1: 1 % cholesterol with methanol extract of P.s (62.5 mg/kg); (iv) PM2: 1 % cholesterol with methanol extract of P.s (125 mg/kg); (v) PM3: 1 % cholesterol with methanol extract of P.s (250 mg/kg); (vi) SMV group fed 1 % cholesterol supplemented with Simvistatin drug (1.2 mg/kg). All animals were treated for 10 weeks. At the end of the treatment, the rabbits were fasted and sacrificed and the aortic tissues were collected for histological studies to measure the area of the neointimal foam cell infiltration using software. The thickening of intima ratio of atherosclerosis and morphological changes by scanning electron microscope were measured. The results showed that the atherosclerotic group had significantly bigger area of fatty streak compared to the control group. The area of fatty streak in the abdominal aorta was significantly reduced in the treatment groups which were similar with the SMV group. Similarly, there was a reduction in the number of foam cell in the treatment groups compared to the atherosclerotic group as seen under scanning microscope. In conclusion, histological study demonstrated that the methanol extract of the P.s could reduce the neointimal foam cell infiltration in the lumen of the aorta and the atherosclerotic lesion. PMID:27366140

  5. Autoantibody production in rabbits

    PubMed Central

    Asherson, G. L.; Holborow, E. J.

    1966-01-01

    Rabbits received two injections of dead bacteria in Freund's complete adjuvant. One month later the sera of the rabbits were examined for autoantibodies against gut by indirect immunofluorescence using the rabbit's own stomach, ileum and colon taken at post mortem. Autoantibodies against colon were found in three out of seven rabbits injected with one particular strain of Escherichia coli O64 and in a few animals injected with other E. coli, Salmonella arizona, Proteus mirabilis, Klebsiella pneumoniae and Streptococcus faecalis. The antigen, with which the autoantibodies reacted, behaved like mucus and was detected in the colon and sometimes in the ileum and the stomach. Three patterns of staining were observed: (a) staining of the superficial mucosa of the colon with sparing of the deep glands; (b) staining of scattered groups of glands in the deepest part of the colon with sparing of the superficial glands (this pattern of staining was associated with staining of the superficial mucosa of the body of the stomach); and (c) staining of both the superficial and deep glands of the colon. None of the sera tested reacted with the bronchial or salivary glands. Polysaccharide preparations of the colon, but not the stomach, inhibited the reaction of the autoantibodies with colon in the sera tested. The amount of antigen needed to inhibit the basal staining was much greater than that needed to inhibit the superficial staining. It was concluded that rabbits may produce autoantibodies to colon and in some cases to ileum and stomach following the injection of certain dead bacteria in Freund's complete adjuvant. ImagesFIGS. 1-2FIG. 3FIG. 4FIG. 5FIG. 6 PMID:4956607

  6. Research Progress on the Risk Factors and Outcomes of Human Carotid Atherosclerotic Plaques

    PubMed Central

    Xiong, Xiang-Dong; Xiong, Wei-Dong; Xiong, Shang-Shen; Chen, Gui-Hai

    2017-01-01

    Objective: Atherosclerosis is an inflammatory process that results in complex lesions or plaques that protrude into the arterial lumen. Carotid atherosclerotic plaque rupture, with distal atheromatous debris embolization, causes cerebrovascular events. This review aimed to explore research progress on the risk factors and outcomes of human carotid atherosclerotic plaques, and the molecular and cellular mechanisms of human carotid atherosclerotic plaque vulnerability for therapeutic intervention. Data Sources: We searched the PubMed database for recently published research articles up to June 2016, with the key words of “risk factors”, “outcomes”, “blood components”, “molecular mechanisms”, “cellular mechanisms”, and “human carotid atherosclerotic plaques”. Study Selection: The articles, regarding the latest developments related to the risk factors and outcomes, atherosclerotic plaque composition, blood components, and consequences of human carotid atherosclerotic plaques, and the molecular and cellular mechanisms of human carotid atherosclerotic plaque vulnerability for therapeutic intervention, were selected. Results: This review described the latest researches regarding the interactive effects of both traditional and novel risk factors for human carotid atherosclerotic plaques, novel insights into human carotid atherosclerotic plaque composition and blood components, and consequences of human carotid atherosclerotic plaque. Conclusion: Carotid plaque biology and serologic biomarkers of vulnerability can be used to predict the risk of cerebrovascular events. Furthermore, plaque composition, rather than lesion burden, seems to most predict rupture and subsequent thrombosis. PMID:28303857

  7. Imaging Modalities to Identity Inflammation in an Atherosclerotic Plaque

    PubMed Central

    Goel, Sunny; Miller, Avraham; Agarwal, Chirag; Zakin, Elina; Acholonu, Michael; Gidwani, Umesh; Sharma, Abhishek; Kulbak, Guy; Shani, Jacob; Chen, On

    2015-01-01

    Atherosclerosis is a chronic, progressive, multifocal arterial wall disease caused by local and systemic inflammation responsible for major cardiovascular complications such as myocardial infarction and stroke. With the recent understanding that vulnerable plaque erosion and rupture, with subsequent thrombosis, rather than luminal stenosis, is the underlying cause of acute ischemic events, there has been a shift of focus to understand the mechanisms that make an atherosclerotic plaque unstable or vulnerable to rupture. The presence of inflammation in the atherosclerotic plaque has been considered as one of the initial events which convert a stable plaque into an unstable and vulnerable plaque. This paper systemically reviews the noninvasive and invasive imaging modalities that are currently available to detect this inflammatory process, at least in the intermediate stages, and discusses the ongoing studies that will help us to better understand and identify it at the molecular level. PMID:26798515

  8. Automatic classification of atherosclerotic plaques imaged with intravascular OCT

    PubMed Central

    Rico-Jimenez, Jose J.; Campos-Delgado, Daniel U.; Villiger, Martin; Otsuka, Kenichiro; Bouma, Brett E.; Jo, Javier A.

    2016-01-01

    Intravascular optical coherence tomography (IV-OCT) allows evaluation of atherosclerotic plaques; however, plaque characterization is performed by visual assessment and requires a trained expert for interpretation of the large data sets. Here, we present a novel computational method for automated IV-OCT plaque characterization. This method is based on the modeling of each A-line of an IV-OCT data set as a linear combination of a number of depth profiles. After estimating these depth profiles by means of an alternating least square optimization strategy, they are automatically classified to predefined tissue types based on their morphological characteristics. The performance of our proposed method was evaluated with IV-OCT scans of cadaveric human coronary arteries and corresponding tissue histopathology. Our results suggest that this methodology allows automated identification of fibrotic and lipid-containing plaques. Moreover, this novel computational method has the potential to enable high throughput atherosclerotic plaque characterization. PMID:27867716

  9. Intravascular photoacoustic tomography for characterization of atherosclerotic lipid and inflammation

    NASA Astrophysics Data System (ADS)

    Zhang, Jian; Qin, Huan; Shi, Yujiao; Yang, Sihua; Xing, Da

    2014-09-01

    Photoacoustic imaging is a fast growing imaging technology depending on its high optical resolution of optics while taking the advantage of the high penetration depth of ultrasound. In this paper, we demonstrate the new progress in the photoacoustic imaging. Atherosclerosis is characterized by a progressive build-up of lipid in the arterial wall, which is known as plaque. Histological studies demonstrate that the primary cause of acute cardiovascular events is the rupture of atherosclerotic plaques. Lipid and inflammation within the plaque are related to influence the propensity of plaques to disrupt. Photoacoustic intravascular tomography (IVPAT) holds a great advantage in providing comprehensive morphological and functional information of plaques. Lipid relative concentration maps of atherosclerotic aorta were obtained and compared with histology. Furthermore, by selectively targeting the intravascular inflammatory cytokines, IVPAT is also capable of mapping the inflamed area and determining the degree of inflammation.

  10. Adventitial inflammation and its interaction with intimal atherosclerotic lesions

    PubMed Central

    Akhavanpoor, Mohammadreza; Wangler, Susanne; Gleissner, Christian A.; Korosoglou, Grigorios; Katus, Hugo A.; Erbel, Christian

    2014-01-01

    The presence of adventitial inflammation in correlation with atherosclerotic lesions has been recognized for decades. In the last years, several studies have investigated the relevance and impact of adventitial inflammation on atherogenesis. In the abdominal aorta of elderly Apoe−/− mice, adventitial inflammatory structures were characterized as organized ectopic lymphoid tissue, and therefore termed adventitial tertiary lymphoid organs (ATLOs). These ATLOs possess similarities in development, structure and function to secondary lymphoid organs. A crosstalk between intimal atherosclerotic lesions and ATLOs has been suggested, and several studies could demonstrate a potential role for medial vascular smooth muscle cells in this process. We here review the development, phenotypic characteristics, and function of ATLOs in atherosclerosis. Furthermore, we discuss the possible role of medial vascular smooth muscle cells and their interaction between plaque and ATLOs. PMID:25152736

  11. Iodine-125 cholesteryl iopanoate for measuring extent of atherosclerosis in rabbits.

    PubMed

    DeGalan, M R; Schwendner, S W; Skinner, R W; Longino, M A; Gross, M; Counsell, R E

    1988-04-01

    Rabbits rendered atherosclerotic by mechanical aortic de-endothelialization and 6 wk of cholesterol feeding were administered estradiol-17 beta-cypionate, an anti-atherogenic agent in rabbits. These animals were compared to a similar, untreated group and control animals fed a regular non-atherogenic diet. Iodine-125 cholesteryl iopanoate ([125I]Cl), a nonhydrolyzable cholesteryl ester derivative, was administered intravenously at regular intervals throughout the study. Six days after the last dose of [125I]Cl, the animals were scanned with a gamma camera. After animals were killed, tissue distribution of the 125I radioactivity showed a significant decrease of [125I]CI accumulation in the aorta of estrogen-treated as compared to untreated, cholesterol-fed animals. However, the accumulation of [125I]CI in the aortas was insufficient to accurately define the presence of atheroma by gamma camera scintigraphy.

  12. Molecular aspects of anti-atherosclerotic effects of short peptides.

    PubMed

    Khavinson, V Kh; Lin'kova, N S; Evlashkina, E V; Durnova, A O; Kozlov, K L; Gutop, O E

    2014-11-01

    We studied molecular mechanisms of the vasoprotective effects of tripeptide T-38 and dipeptide RR-1. Short peptides T-38 and the RR-1 activate the processes of cell renewal in organotypic and dissociated cultures of vascular cells during aging by increasing the expression of Ki-67 and reducing the synthesis of p53 protein. T-38 and RR-1 reduce the synthesis of E-selectin, adhesion molecule involved in the formation of atherosclerotic plaques.

  13. From Lipids to Inflammation: New Approaches to Reducing Atherosclerotic Risk.

    PubMed

    Shapiro, Michael D; Fazio, Sergio

    2016-02-19

    The introduction of statins ≈ 30 years ago ushered in the era of lipid lowering as the most effective way to reduce risk of atherosclerotic cardiovascular disease. Nonetheless, residual risk remains high, and statin intolerance is frequently encountered in clinical practice. After a long dry period, the field of therapeutics targeted to lipids and atherosclerosis has entered a renaissance. Moreover, the demonstration of clinical benefits from the addition of ezetimibe to statin therapy in subjects with acute coronary syndromes has renewed the enthusiasm for the cholesterol hypothesis and the hope that additional agents that lower low-density lipoprotein will decrease risk of atherosclerotic cardiovascular disease. Drugs in the orphan disease category are now available for patients with the most extreme hypercholesterolemia. Furthermore, discovery and rapid translation of a novel biological pathway has given rise to a new class of cholesterol-lowering drugs, the proprotein convertase subtilisin kexin-9 inhibitors. Trials of niacin added to statin have failed to demonstrate cardiac benefits, and 3 cholesterol ester transfer protein inhibitors have also failed to reduce atherosclerotic cardiovascular disease risk, despite producing substantial increases in HDL levels. Although the utility of triglyceride-lowering therapies remains uncertain, 2 large clinical trials are testing the influence of omega-3 polyunsaturated fatty acids on atherosclerotic events in hypertriglyceridemia. Novel antisense therapies targeting apolipoprotein C-III (for triglyceride reduction) and apo(a) (for lipoprotein(a) reduction) are showing a promising trajectory. Finally, 2 large clinical trials are formally putting the inflammatory hypothesis of atherosclerosis to the test and may open a new avenue for cardiovascular disease risk reduction.

  14. Vulnerable atherosclerotic plaque detection by resonance Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Liu, Cheng-hui; Boydston-White, Susie; Weisberg, Arel; Wang, Wubao; Sordillo, Laura A.; Perotte, Adler; Tomaselli, Vincent P.; Sordillo, Peter P.; Pei, Zhe; Shi, Lingyan; Alfano, Robert R.

    2016-12-01

    A clear correlation has been observed between the resonance Raman (RR) spectra of plaques in the aortic tunica intimal wall of a human corpse and three states of plaque evolution: fibrolipid plaques, calcified and ossified plaques, and vulnerable atherosclerotic plaques (VPs). These three states of atherosclerotic plaque lesions demonstrated unique RR molecular fingerprints from key molecules, rendering their spectra unique with respect to one another. The vibrational modes of lipids, cholesterol, carotenoids, tryptophan and heme proteins, the amide I, II, III bands, and methyl/methylene groups from the intrinsic atherosclerotic VPs in tissues were studied. The salient outcome of the investigation was demonstrating the correlation between RR measurements of VPs and the thickness measurements of fibrous caps on VPs using standard histopathology methods, an important metric in evaluating the stability of a VP. The RR results show that VPs undergo a structural change when their caps thin to 66 μm, very close to the 65-μm empirical medical definition of a thin cap fibroatheroma plaque, the most unstable type of VP.

  15. The NADPH oxidase Nox4 has anti-atherosclerotic functions

    PubMed Central

    Schürmann, Christoph; Rezende, Flavia; Kruse, Christoph; Yasar, Yakub; Löwe, Oliver; Fork, Christian; van de Sluis, Bart; Bremer, Rolf; Weissmann, Norbert; Shah, Ajay M.; Jo, Hanjoong; Brandes, Ralf P.; Schröder, Katrin

    2015-01-01

    Aims Oxidative stress is thought to be a risk for cardiovascular disease and NADPH oxidases of the Nox family are important producers of reactive oxygen species. Within the Nox family, the NADPH oxidase Nox4 has a unique position as it is constitutively active and produces H2O2 rather than O2− . Nox4 is therefore incapable of scavenging NO and its low constitutive H2O2 production might even be beneficial. We hypothesized that Nox4 acts as an endogenous anti-atherosclerotic enzyme. Methods and results Tamoxifen-induced Nox4-knockout mice were crossed with ApoE−/− mice and spontaneous atherosclerosis under regular chow as well as accelerated atherosclerosis in response to partial carotid artery ligation under high-fat diet were determined. Deletion of Nox4 resulted in increased atherosclerosis formation in both models. Mechanistically, pro-atherosclerotic and pro-inflammatory changes in gene expression were observed prior to plaque development. Moreover, inhibition of Nox4 or deletion of the enzyme in the endothelium but not in macrophages resulted in increased adhesion of macrophages to the endothelial surface. Conclusions The H2O2-producing NADPH oxidase Nox4 is an endogenous anti-atherosclerotic enzyme. Nox4 inhibitors, currently under clinical evaluation, should be carefully monitored for cardiovascular side-effects. PMID:26385958

  16. Uniaxial tensile testing approaches for characterisation of atherosclerotic plaques.

    PubMed

    Walsh, M T; Cunnane, E M; Mulvihill, J J; Akyildiz, A C; Gijsen, F J H; Holzapfel, G A

    2014-03-03

    The pathological changes associated with the development of atherosclerotic plaques within arterial vessels result in significant alterations to the mechanical properties of the diseased arterial wall. There are several methods available to characterise the mechanical behaviour of atherosclerotic plaque tissue, and it is the aim of this paper to review the use of uniaxial mechanical testing. In the case of atherosclerotic plaques, there are nine studies that employ uniaxial testing to characterise mechanical behaviour. A primary concern regarding this limited cohort of published studies is the wide range of testing techniques that are employed. These differing techniques have resulted in a large variance in the reported data making comparison of the mechanical behaviour of plaques from different vasculatures, and even the same vasculature, difficult and sometimes impossible. In order to address this issue, this paper proposes a more standardised protocol for uniaxial testing of diseased arterial tissue that allows for better comparisons and firmer conclusions to be drawn between studies. To develop such a protocol, this paper reviews the acquisition and storage of the tissue, the testing approaches, the post-processing techniques and the stress-strain measures employed by each of the nine studies. Future trends are also outlined to establish the role that uniaxial testing can play in the future of arterial plaque mechanical characterisation.

  17. Artery buckling affects the mechanical stress in atherosclerotic plaques

    PubMed Central

    2015-01-01

    Background Tortuous arteries are often seen in patients with hypertension and atherosclerosis. While the mechanical stress in atherosclerotic plaque under lumen pressure has been studied extensively, the mechanical stability of atherosclerotic arteries and subsequent effect on the plaque stress remain unknown. To this end, we investigated the buckling and post-buckling behavior of model stenotic coronary arteries with symmetric and asymmetric plaque. Methods Buckling analysis for a model coronary artery with symmetric and asymmetric plaque was conducted using finite element analysis based on the dimensions and nonlinear anisotropic materials properties reported in the literature. Results Artery with asymmetric plaque had lower critical buckling pressure compared to the artery with symmetric plaque and control artery. Buckling increased the peak stress in the plaque and led to the development of a high stress concentration in artery with asymmetric plaque. Stiffer calcified tissue and severe stenosis increased the critical buckling pressure of the artery with asymmetric plaque. Conclusions Arteries with atherosclerotic plaques are prone to mechanical buckling which leads to a high stress concentration in the plaques that can possibly make the plaques prone to rupture. PMID:25603490

  18. Stress analysis of fracture of atherosclerotic plaques: crack propagation modeling.

    PubMed

    Rezvani-Sharif, Alireza; Tafazzoli-Shadpour, Mohammad; Kazemi-Saleh, Davood; Sotoudeh-Anvari, Maryam

    2016-12-09

    Traditionally, the degree of luminal obstruction has been used to assess the vulnerability of atherosclerotic plaques. However, recent studies have revealed that other factors such as plaque morphology, material properties of lesion components and blood pressure may contribute to the fracture of atherosclerotic plaques. The aim of this study was to investigate the mechanism of fracture of atherosclerotic plaques based on the mechanical stress distribution and fatigue analysis by means of numerical simulation. Realistic models of type V plaques were reconstructed based on histological images. Finite element method was used to determine mechanical stress distribution within the plaque. Assuming that crack propagation initiated at the sites of stress concentration, crack propagation due to pulsatile blood pressure was modeled. Results showed that crack propagation considerably changed the stress field within the plaque and in some cases led to initiation of secondary cracks. The lipid pool stiffness affected the location of crack formation and the rate and direction of crack propagation. Moreover, increasing the mean or pulse pressure decreased the number of cycles to rupture. It is suggested that crack propagation analysis can lead to a better recognition of factors involved in plaque rupture and more accurate determination of vulnerable plaques.

  19. From rabbit antibody repertoires to rabbit monoclonal antibodies

    PubMed Central

    Weber, Justus; Peng, Haiyong; Rader, Christoph

    2017-01-01

    In this review, we explain why and how rabbit monoclonal antibodies have become outstanding reagents for laboratory research and increasingly for diagnostic and therapeutic applications. Starting with the unique ontogeny of rabbit B cells that affords highly distinctive antibody repertoires rich in in vivo pruned binders of high diversity, affinity and specificity, we describe the generation of rabbit monoclonal antibodies by hybridoma technology, phage display and alternative methods, along with an account of successful humanization strategies. PMID:28336958

  20. Endovascular Management of Atherosclerotic Renal Artery Stenosis: Post-Cardiovascular Outcomes in Renal Atherosclerotic Lesions Era Winner or False Alarm?

    PubMed Central

    Karanikola, Evridiki; Karaolanis, Georgios; Galyfos, George; Barbaressos, Emmanuel; Palla, Viktoria; Filis, Konstantinos

    2017-01-01

    Renal artery stenosis (RAS) is frequently associated with severe comorbidities such as reduced renal perfusion, hypertension, and end-stage renal failure. In approximately 90% of patients, renal artery atherosclerosis is the main cause for RAS, and it is associated with an increased risk for fatal and non-fatal cardiovascular and renal complications. Endovascular management of atherosclerotic RAS (ARAS) has been recently evaluated by several randomized controlled trials that failed to demonstrate benefit of stenting. Furthermore, the Cardiovascular Outcomes in Renal Atherosclerotic Lesions study did not demonstrate any benefit over the revascularization approach. In this review, we summarized the available data from retrospective, prospective and randomized trials on ARAS to provide clinicians with sufficient data in order to produce useful conclusions for everyday clinical practice. PMID:28377906

  1. [Anti-atherosclerotic effects of peptidic geroprotector].

    PubMed

    Ryzhak, A P; Kuznik, B I; Putkovskaia, V N; Ryzhak, G A

    2012-01-01

    The study of peptide geroprotector's biological activity was conducted on basis of calf aorta extract Slavinorm in experimental models of hiperlypidemia and acute myocardial infarction. The study results show that Slavinorm possesses the evident antiatherogenic effect. It appears in blood lipid spectrum parameters optimization, including atherogenic coefficient normalization at the expense of high density lipids level increase and other cholesterol fractions decrease. Slavinorm manifested antiischemic effects in the model of acute myocardial infarction, which was expressed in significant decrease of necrotic zone after 4-hours coronary artery occlusion in comparison with parameters in control animals and in low frequency of postobstructive arythmia.

  2. Rabbits killing birds revisited.

    PubMed

    Zhang, Jimin; Fan, Meng; Kuang, Yang

    2006-09-01

    We formulate and study a three-species population model consisting of an endemic prey (bird), an alien prey (rabbit) and an alien predator (cat). Our model overcomes several model construction problems in existing models. Moreover, our model generates richer, more reasonable and realistic dynamics. We explore the possible control strategies to save or restore the bird by controlling or eliminating the rabbit or the cat when the bird is endangered. We confirm the existence of the hyperpredation phenomenon, which is a big potential threat to most endemic prey. Specifically, we show that, in an endemic prey-alien prey-alien predator system, eradication of introduced predators such as the cat alone is not always the best solution to protect endemic insular prey since predator control may fail to protect the indigenous prey when the control of the introduced prey is not carried out simultaneously.

  3. Rabbit renotropic system

    SciTech Connect

    Areas, J.; Yun, G.C.; Rahmat, J.; Gersten, D.; Goel, R.; Preuss, H.G.

    1988-04-01

    Elevated levels of a specific renal growth factor, renotropin, have been associated with spontaneous hypertension. To examine this association more closely, we have undertaken the development of a better assay system to characterize and purify renotropin. Sera from rabbits prior to operation (control) and at a specified time after unilateral nephrectomy (uni) were examined for renotropic activity. Comparing the effects of uni to control sera in the same rabbit, significant stimulation of 3H-thymidine incorporation into the DNA of primary rabbit kidney cultures incubated in D-valine medium to eliminate fibroblast growth was noted: at 3 days postoperatively 73% (n = 13), at 7 days 103% (n = 39), at 10 days 130% (n = 31), at 21 days 101% (n = 24), at 42 days 89% (n = 13). All values were at least P less than 0.01. The stimulatory properties were dose-dependent but reached a plateau at high serum concentrations. Comparing CPM/mg protein in uni/control in different concentrations of sera 7 days postoperatively, uni versus control were 67/44 at 5% v/v, 139/72 at 10% v/v, 261/161 at 20% v/v, and 243/136 at 40% v/v. The renotropic effect of uni sera remained after dialysis in incubation medium and after sera were heated in boiling water for 5 minutes. Renal extracts obtained from growing kidneys 7 days postnephrectomy augmented renotropic activity. Atrial natriuretic factor, ouabain, PGF2 alpha, PGE1, and cAMP did not possess renotropic activity. We conclude that the primary rabbit kidney culture assay for renotropin is highly sensitive and will be an important tool to comprehend the role of renotropin in the pathogenesis of hypertension.

  4. Effect of vitamin E in the treatment of bovine-albumin-induced uveitis in rabbits.

    PubMed

    Yücel, I; Paksoy, N; Yücel, G; Aksu, G; Aksu, T A

    1992-01-01

    In order to assess the role of vitamin E, an antioxidant, in the treatment of uveitis, a controlled experimental study was carried out on 20 New Zealand albino rabbits with bovine-albumin-induced uveitis. In all vitamin-E-treated animals, clinical and histopathological study of the retina and uvea revealed no significant changes in comparison with those in untreated rabbits.

  5. Computational Hemodynamic Analysis for the Diagnosis of Atherosclerotic Changes in Intracranial Aneurysms: A Proof-of-Concept Study Using 3 Cases Harboring Atherosclerotic and Nonatherosclerotic Aneurysms Simultaneously

    PubMed Central

    Endo, Hidenori; Niizuma, Kuniyasu; Endo, Toshiki; Funamoto, Kenichi; Ohta, Makoto; Tominaga, Teiji

    2016-01-01

    This was a proof-of-concept computational fluid dynamics (CFD) study designed to identify atherosclerotic changes in intracranial aneurysms. We selected 3 patients with multiple unruptured aneurysms including at least one with atherosclerotic changes and investigated whether an image-based CFD study could provide useful information for discriminating the atherosclerotic aneurysms. Patient-specific geometries were constructed from three-dimensional data obtained using rotational angiography. Transient simulations were conducted under patient-specific inlet flow rates measured by phase-contrast magnetic resonance velocimetry. In the postanalyses, we calculated time-averaged wall shear stress (WSS), oscillatory shear index, and relative residence time (RRT). The volume of blood flow entering aneurysms through the neck and the mean velocity of blood flow inside aneurysms were examined. We applied the age-of-fluid method to quantitatively assess the residence of blood inside aneurysms. Atherosclerotic changes coincided with regions exposed to disturbed blood flow, as indicated by low WSS and long RRT. Blood entered aneurysms in phase with inlet flow rates. The mean velocities of blood inside atherosclerotic aneurysms were lower than those inside nonatherosclerotic aneurysms. Blood in atherosclerotic aneurysms was older than that in nonatherosclerotic aneurysms, especially near the wall. This proof-of-concept study demonstrated that CFD analysis provided detailed information on the exchange and residence of blood that is useful for the diagnosis of atherosclerotic changes in intracranial aneurysms. PMID:27703491

  6. Delineation of atherosclerotic plaque using subharmonic imaging filtering techniques and a commercial intravascular ultrasound system.

    PubMed

    Sridharan, Anush; Eisenbrey, John R; Machado, Priscilla; deMuinck, Ebo D; Doyley, Marvin M; Forsberg, Flemming

    2013-01-01

    The ability to delineate atherosclerotic plaque from the surrounding tissue using custom-developed subharmonic imaging (SHI) digital filtering techniques was investigated in vivo using a commercially available system. Atherosclerosis was induced in the aorta of two Watanabe Heritable Hyperlipidemic rabbits following which injections of an ultrasound contrast agent (UCA) Definity (Lantheus Medical Imaging, N Billerica, Massachusetts) were administered. Imaging was performed using a Galaxy intravascular ultrasound (IVUS) scanner (Boston Scientific, Natick, Massachusetts) equipped with an Atlantis® SR Pro Imaging Catheter (Boston Scientific). Four preliminary band-pass filters were designed to isolate the subharmonic signal (from surrounding tissue) and applied to the radio-frequency (RF) data. Preliminary filter performances were compared in terms of vessel-tissue contrast-to-tissue ratio (CTR) and visual examination. Based on preliminary results, a subharmonic adaptive filter and a stopband (SB) filter were designed and applied to the RF data. Images were classified as fundamental, SHI, and SB. Four readers performed qualitative analysis of 168 randomly selected images (across all three imaging modes). The images were scored for overall image quality, image noise, plaque visualization, and vessel lumen visualization. A Wilcoxon signed-rank test was used to compare the scores followed by intraclass correlation (ICC) evaluation. Quantitative analysis was performed by calculating the CTRs for the vessel-to-plaque and vessel-to-tissue (compared using a paired student's t test). Qualitative analysis showed SHI and SB to have significantly less image noise relative to the fundamental mode (p < 0.001). Fundamental mode scored significantly higher than SHI and SB for the remaining three categories. ICC showed mixed results among reader evaluation for delineation of plaque. However, quantitatively, SHI produced the best vessel-plaque CTR.

  7. Transgenic Rabbits Expressing Ovine PrP Are Susceptible to Scrapie.

    PubMed

    Sarradin, Pierre; Viglietta, Céline; Limouzin, Claude; Andréoletti, Olivier; Daniel-Carlier, Nathalie; Barc, Céline; Leroux-Coyau, Mathieu; Berthon, Patricia; Chapuis, Jérôme; Rossignol, Christelle; Gatti, Jean-Luc; Belghazi, Maya; Labas, Valérie; Vilotte, Jean-Luc; Béringue, Vincent; Lantier, Frédéric; Laude, Hubert; Houdebine, Louis-Marie

    2015-08-01

    Transmissible spongiform encephalopathies (TSEs) are a group of neurodegenerative diseases affecting a wide range of mammalian species. They are caused by prions, a proteinaceous pathogen essentially composed of PrPSc, an abnormal isoform of the host encoded cellular prion protein PrPC. Constrained steric interactions between PrPSc and PrPC are thought to provide prions with species specificity, and to control cross-species transmission into other host populations, including humans. Transgenetic expression of foreign PrP genes has been successfully and widely used to overcome the recognized resistance of mouse to foreign TSE sources. Rabbit is one of the species that exhibit a pronounced resistance to TSEs. Most attempts to infect experimentally rabbit have failed, except after inoculation with cell-free generated rabbit prions. To gain insights on the molecular determinants of the relative resistance of rabbits to prions, we generated transgenic rabbits expressing the susceptible V136R154Q171 allele of the ovine PRNP gene on a rabbit wild type PRNP New Zealand background and assessed their experimental susceptibility to scrapie prions. All transgenic animals developed a typical TSE 6-8 months after intracerebral inoculation, whereas wild type rabbits remained healthy more than 700 days after inoculation. Despite the endogenous presence of rabbit PrPC, only ovine PrPSc was detectable in the brains of diseased animals. Collectively these data indicate that the low susceptibility of rabbits to prion infection is not enciphered within their non-PrP genetic background.

  8. Fine structures around the orifice of the intercostal artery of the rabbit thoracic aorta.

    PubMed

    Emura, S; Masuko, S; Sunaga, T

    1992-03-01

    In hypercholesterolemic rabbits, atherosclerotic lesions easily occur in the thoracic aorta, especially at the distal and lateral sides of the walls around the orifices of the dorsal intercostal arteries. In order to examine whether some special structures that lead to atherosclerotic lesions are present even in normal conditions, the authors investigated the morphologic features around the orifice of the intercostal artery of 20 normal rabbit aortae under electron microscopy. The endothelial cells were generally fusiform but tended to be round and have a cobblestone-like appearance at the lateral side. There was intimal protrusion at the distal and lateral sides of the orifice, where the distribution and arrangement of elastic fibers and smooth muscle cells were different from those at the proximal side. At the proximal edge of the orifice, elastic fibers formed a thick plate-like internal elastic lamina beneath the endothelial cells. On the other hand, at the distal and lateral sides, elastic fibers formed close-meshed structures over the proper plate-like internal elastic lamina. These results indicate that the aortic walls at the distal and lateral sides of the orifice are structurally different from those at other regions even in normal conditions and suggest the involvement of special structures at the distal and lateral sides of the orifice in atherogenesis.

  9. Three-dimensional dynamic contrast-enhanced MRI for the accurate, extensive quantification of microvascular permeability in atherosclerotic plaques.

    PubMed

    Calcagno, Claudia; Lobatto, Mark E; Dyvorne, Hadrien; Robson, Philip M; Millon, Antoine; Senders, Max L; Lairez, Olivier; Ramachandran, Sarayu; Coolen, Bram F; Black, Alexandra; Mulder, Willem J M; Fayad, Zahi A

    2015-10-01

    Atherosclerotic plaques that cause stroke and myocardial infarction are characterized by increased microvascular permeability and inflammation. Dynamic contrast-enhanced MRI (DCE-MRI) has been proposed as a method to quantify vessel wall microvascular permeability in vivo. Until now, most DCE-MRI studies of atherosclerosis have been limited to two-dimensional (2D) multi-slice imaging. Although providing the high spatial resolution required to image the arterial vessel wall, these approaches do not allow the quantification of plaque permeability with extensive anatomical coverage, an essential feature when imaging heterogeneous diseases, such as atherosclerosis. To our knowledge, we present the first systematic evaluation of three-dimensional (3D), high-resolution, DCE-MRI for the extensive quantification of plaque permeability along an entire vascular bed, with validation in atherosclerotic rabbits. We compare two acquisitions: 3D turbo field echo (TFE) with motion-sensitized-driven equilibrium (MSDE) preparation and 3D turbo spin echo (TSE). We find 3D TFE DCE-MRI to be superior to 3D TSE DCE-MRI in terms of temporal stability metrics. Both sequences show good intra- and inter-observer reliability, and significant correlation with ex vivo permeability measurements by Evans Blue near-infrared fluorescence (NIRF). In addition, we explore the feasibility of using compressed sensing to accelerate 3D DCE-MRI of atherosclerosis, to improve its temporal resolution and therefore the accuracy of permeability quantification. Using retrospective under-sampling and reconstructions, we show that compressed sensing alone may allow the acceleration of 3D DCE-MRI by up to four-fold. We anticipate that the development of high-spatial-resolution 3D DCE-MRI with prospective compressed sensing acceleration may allow for the more accurate and extensive quantification of atherosclerotic plaque permeability along an entire vascular bed. We foresee that this approach may allow for

  10. Early extracellular and cellular lipid deposits in aorta of cholesterol-fed rabbits.

    PubMed Central

    Guyton, J. R.; Klemp, K. F.

    1992-01-01

    Subendothelial accumulation of extracellular liposomes rich in unesterified cholesterol has been described as an early feature of atherosclerosis induced by cholesterol feeding in rabbits. Beta-very-low-density lipoproteins, however, the presumed source of atherogenic lipid in this animal model, contain mostly esterified cholesterol. The purpose of this study was to test for the presence of extracellular neutral lipid deposits consistent with esterified cholesterol, by employing new electron microscopic techniques. Rabbits were fed 0.5% cholesterol, 5% butter for 0, 1, 2, and 4 weeks. The lipid-preserving ultrastructural techniques showed, in control and atherosclerotic rabbit arteries, neutral lipid droplets adherent to the endothelial luminal surface. After 1 to 2 weeks, subendothelial extracellular deposits of mostly membranous lipid appeared; these deposits contained variable amounts of neutral lipid. At the same time, cytoplasmic neutral lipid droplets appeared in smooth muscle cells and in a small number of subendothelial macrophagelike cells. After 4 weeks, monocytic infiltration and macrophage foam cell development were prominent, but abundant extracellular lipid deposits also were found. Therefore, in arteries of cholesterol-fed rabbits, deposition of membranous and neutral lipid in the extracellular space and neutral lipid accumulation in resident arterial cells are early and probably independent events, both occurring before monocytic infiltration of the arterial intima. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 PMID:1415485

  11. Recombinant Rabbit Leukemia Inhibitory Factor and Rabbit Embryonic Fibroblasts Support the Derivation and Maintenance of Rabbit Embryonic Stem Cells

    PubMed Central

    Xue, Fei; Ma, Yinghong; Chen, Y. Eugene; Zhang, Jifeng; Lin, Tzu-An; Chen, Chien-Hong; Lin, Wei-Wen; Roach, Marsha; Ju, Jyh-Cherng; Yang, Lan; Du, Fuliang

    2012-01-01

    Abstract The rabbit is a classical experimental animal species. A major limitation in using rabbits for biomedical research is the lack of germ-line-competent rabbit embryonic stem cells (rbESCs). We hypothesized that the use of homologous feeder cells and recombinant rabbit leukemia inhibitory factor (rbLIF) might improve the chance in deriving germ-line-competent rbES cells. In the present study, we established rabbit embryonic fibroblast (REF) feeder layers and synthesized recombinant rbLIF. We derived a total of seven putative rbESC lines, of which two lines (M5 and M23) were from culture Condition I using mouse embryonic fibroblasts (MEFs) as feeders supplemented with human LIF (hLIF) (MEF+hLIF). Another five lines (R4, R9, R15, R21, and R31) were derived from Condition II using REFs as feeder cells supplemented with rbLIF (REF+rbLIF). Similar derivation efficiency was observed between these two conditions (8.7% vs. 10.2%). In a separate experiment with 2×3 factorial design, we examined the effects of feeder cells (MEF vs. REF) and LIFs (mLIF, hLIF vs. rbLIF) on rbESC culture. Both Conditions I and II supported satisfactory rbESC culture, with similar or better population doubling time and colony-forming efficiency than other combinations of feeder cells with LIFs. Rabbit ESCs derived and maintained on both conditions displayed typical ESC characteristics, including ESC pluripotency marker expression (AP, Oct4, Sox2, Nanog, and SSEA4) and gene expression (Oct4, Sox2, Nanog, c-Myc, Klf4, and Dppa5), and the capacity to differentiate into three primary germ layers in vitro. The present work is the first attempt to establish rbESC lines using homologous feeder cells and recombinant rbLIF, by which the rbESCs were derived and maintained normally. These cell lines are unique resources and may facilitate the derivation of germ-line-competent rbESCs. PMID:22775411

  12. Apoptosis of peripheral blood leucocytes in rabbits infected with different strains of rabbit haemorrhagic disease virus.

    PubMed

    Niedźwiedzka-Rystwej, Paulina; Hukowska-Szematowicz, Beata; Tokarz-Deptuła, Beata; Trzeciak-Ryczek, Alicja; Działo, Joanna; Deptuła, Wiesław

    2013-01-01

    The pathogenicity of RHDV (rabbit haemorrhagic disease virus) is mainly associated with its affinity to blood vessels, with causing disseminated intravascular coagulations (DIC), and with the stimulation of the host immune system. Moreover, there are implications suggesting that apoptosis may be a pivotal process in understanding the basis of viral haemorrhagic disease in rabbits - a serious infectious disease causing mortality to wild and domestic rabbits. The aim of this study is to evaluate, by means of flow cytometry, the dynamics of apoptosis in peripheral blood granulocytes and lymphocytes in rabbits experimentally infected with seven different strains of RHDV and so-called antigenic variants of RHDV denominated as RHDVa, i.e.: Hungarian 24V/89, 1447V/96, 72V/2003; Austrian 01-04, 237/04, V-412 and French 05-01. The results showed that all of the RHDV and RHDVa strains cause an increase in the number of apoptotic cells throughout the infection, which might indicate the need for further analysis of the importance of this process.

  13. Presence of hypochlorite-modified proteins in human atherosclerotic lesions.

    PubMed Central

    Hazell, L J; Arnold, L; Flowers, D; Waeg, G; Malle, E; Stocker, R

    1996-01-01

    Oxidation of LDL may contribute to atherogenesis, though the nature of the in vivo oxidant(s) remains obscure. Myeloperoxidase, the enzyme responsible for hypochlorous acid/hypochlorite (HOCl) production in vivo, is present in active form in human atherosclerotic lesions, and HOCl aggregates and transforms LDL into a high-uptake form for macrophages in vitro. Here we demonstrate HOCl-modified proteins in human lesions using an mAb raised against HOCl-modified LDL that recognizes HOCl-oxidized proteins but does not cross-react with Cu2+-, malondialdehyde-, or 4-hydroxynonenal-modified LDL. This antibody detected significantly more material in advanced atherosclerotic lesions than normal arteries, even though azide and methionine were included during sample work-up to inhibit myeloperoxidase and to scavenge HOCl. The epitope(s) recognized was predominantly cell associated and present in monocyte/macrophages, smooth muscle, and endothelial cells. The intima and cholesterol clefts stained more heavily than the center of the thickened vessels; adventitial staining was apparent in some cases. Immunostaining was also detected in a very early lesion from an accident victim, beside healthy areas that were unreactive. LDL oxidized by HOCl in vitro, but not native LDL, effectively competed with the epitopes in lesions for antibody binding. Density centrifugation of plaque homogenates and Western blot analysis showed that, in the apo B-containing lipoprotein fraction, the mAb recognized protein(s) of molecular mass greater than apo B, similar to those produced during oxidation of LDL with HOCl in vitro. Three major proteins were recognized by the anti-HOCl-modified protein antibody but not by an anti-apo B antibody in the apo B-free fraction. Together, these results demonstrate HOCl-oxidized proteins in human atherosclerotic lesions, implicating this oxidant in LDL modification in vivo. PMID:8617887

  14. Identification of Atherosclerotic Plaques in Carotid Artery by Fluorescence Spectroscopy

    NASA Astrophysics Data System (ADS)

    Rocha, Rick; Villaverde, Antonio Balbin; Silveira, Landulfo; Costa, Maricília Silva; Alves, Leandro Procópio; Pasqualucci, Carlos Augusto; Brugnera, Aldo

    2008-04-01

    The aim of this work was to identify the presence of atherosclerotic plaques in carotid artery using the Fluorescence Spectroscopy. The most important pathogeny in the cardiovascular disorders is the atherosclerosis, which may affect even younger individuals. With approximately 1.2 million heart attacks and 750,000 strokes afflicting an aging American population each year, cardiovascular disease remains the number one cause of death. Carotid artery samples were obtained from the Autopsy Service at the University of São Paulo (São Paulo, SP, Brazil) taken from cadavers. After a histopathological analysis the 60 carotid artery samples were divided into two groups: normal (26) and atherosclerotic plaques (34). Samples were irradiated with the wavelength of 488 nm from an Argon laser. A 600 μm core optical fiber, coupled to the Argon laser, was used for excitation of the sample, whereas another 600 optical fiber, coupled to the spectrograph entrance slit, was used for collecting the fluorescence from the sample. Measurements were taken at different points on each sample and then averaged. Fluorescence spectra showed a single broad line centered at 549 nm. The fluorescence intensity for each sample was calculated by subtracting the intensity at the peak (550 nm) and at the bottom (510 nm) and then data were statistically analyzed, looking for differences between both groups of samples. ANOVA statistical test showed a significant difference (p<0,05) between both types of tissues, with regard to the fluorescence peak intensities. Our results indicate that this technique could be used to detect the presence of the atherosclerotic in carotid tissue.

  15. Apolipoprotein B-containing lipoproteins and atherosclerotic cardiovascular disease

    PubMed Central

    Shapiro, Michael D.; Fazio, Sergio

    2017-01-01

    Cholesterol-rich, apolipoprotein B (apoB)-containing lipoproteins are now widely accepted as the most important causal agents of atherosclerotic cardiovascular disease. Multiple unequivocal and orthogonal lines of evidence all converge on low-density lipoprotein and related particles as being the principal actors in the genesis of atherosclerosis. Here, we review the fundamental role of atherogenic apoB-containing lipoproteins in cardiovascular disease and several other humoral and parietal factors that are required to initiate and maintain arterial degeneration. The biology of foam cells and their interactions with high-density lipoproteins, including cholesterol efflux, are also briefly reviewed. PMID:28299190

  16. Management of hypertriglyceridemia for prevention of atherosclerotic cardiovascular disease.

    PubMed

    Brinton, Eliot A

    2015-05-01

    Mendelian randomization data strongly suggest that hypertriglyceridemia (HTG) causes atherosclerotic cardiovascular disease (ASCVD), and so triglyceride (TG) level-lowering treatment in HTG is now more strongly recommended to address the residual ASCVD risk than has been the case in (generally earlier) published guidelines. Fibrates are the best-established agents for TG level lowering and are generally used as first-line treatment of TG levels greater than 500 mg/dL. Statins are the best-established agents for ASCVD prevention, and so are usually used as first-line treatment of TG levels less than 500 mg/dL.

  17. A Combination of Constitutive Damage Model and Artificial Neural Networks to Characterize the Mechanical Properties of the Healthy and Atherosclerotic Human Coronary Arteries.

    PubMed

    Karimi, Alireza; Rahmati, Seyed Mohammadali; Sera, Toshihiro; Kudo, Susumu; Navidbakhsh, Mahdi

    2017-02-02

    It has been indicated that the content and structure of the elastin and collagen of the arterial wall can subject to a significant alteration due to the atherosclerosis. Consequently, a high tissue stiffness, stress, and even damage/rupture are triggered in the arterial wall. Although many studies so far have been conducted to quantify the mechanical properties of the coronary arteries, none of them consider the role of collagen damage of the healthy and atherosclerotic human coronary arterial walls. Recently, a fiber family-based constitutive equation was proposed to capture the anisotropic mechanical response of the healthy and atherosclerotic human coronary arteries via both the histostructural and uniaxial data. In this study, experimental mechanical measurements along with histological data of the healthy and atherosclerotic arterial walls were employed to determine the constitutive damage parameters and remodeling of the collagen fibers. To do this, the preconditioned arterial tissues were excised from human cadavers within 5-h postmortem, and the mean angle of their collagen fibers was precisely determined. Thereafter, a group of quasistatic axial and circumferential loadings were applied to the arterial walls, and the constrained nonlinear minimization method was employed to identify the arterial parameters according to the axial and circumferential extension data. The remodeling of the collagen fibers during the tensile test was also predicted via Artificial Neural Networks algorithm. Regardless of loading direction, the results presented a noteworthy load-bearing capability and stiffness of the atherosclerotic arteries compared to the healthy ones (P < 0.005). Theoretical fiber angles were found to be consistent with the experimental histological data with less than 2 and 5° difference for the healthy and atherosclerotic arterial walls, respectively. The pseudoelastic damage model data were also compared with that of the experimental data, and

  18. Effect of dietary cholesterol and cholesterol oxides on blood cholesterol, lipids, and the development of atherosclerosis in rabbits.

    PubMed

    Hur, Sun Jin; Min, Byungrok; Nam, Ki Chang; Lee, Eun Joo; Ahn, Dong Uk

    2013-06-17

    Two studies were conducted to determine the effects of dietary cholesterol (CHO) and cholesterol oxides (COPs) on the development of atherosclerosis and the changes in fatty acid and blood characteristics in rabbits. In the first study, forty male New Zealand white rabbits were divided into 5 groups and fed commercial rabbit chow with no added CHO or COPs, 1 g CHO, 0.9 g CHO + 0.1 g COPs, 0.8 g CHO + 0.2 g COPs, or 0.5 g CHO + 0.5 g COPs per kg diet. In the second study, 24 male New Zealand White rabbits were divided into 3 groups and fed a diet containing 2 g CHO, 1.6 g CHO + 0.4 g COPs, or 1.2 g CHO + 0.8 g COPs per kg diet. All diets induced atherosclerotic lesions in the rabbits' ascending thoracic aorta. The serum CHO and triglyceride levels (p < 0.05) increased significantly with the increased levels of CHO in the diets. Dietary CHO or COPs did not influence high-density lipoprotein CHO levels. The ratio of saturated fatty acid to unsaturated fatty acid increased as the level of dietary CHO and COPs increased.

  19. [Experimental study on application recombinant human bone morphogenetic protein 2(rhBMP-2)/poly-lactide-co-glycolic acid (PLGA)/fibrin sealant(FS) on repair of rabbit radial bone defect].

    PubMed

    Fan, Zhongkai; Cao, Yang; Zhang, Zhe; Zhang, Mingchao; Lu, Wei; Tang, Lei; Yao, Qi; Lu, Gang

    2012-10-01

    This paper is aimed to investigate the repair of rabbit radial bone defect by the recombinant human bone morphogenetic protein 2/poly-lactideco-glycolic acid microsphere with fibrin sealant (rhBMP-2/PLGA/FS). The radial bone defect models were prepared using New Zealand white rabbits, which were randomly divided into 3 groups, experiment group which were injected with eMP-2/PLGA/FS at bone defect location, control group which were injected with FS at bone defect location, and blank control group without treatment. The ability of repairing bone defect was evaluated with X-ray radiograph. Bone mineral density in the defect regions was analysed using the level of ossification. The osteogenetic ability of repairing bone defect, the degradation of the material, the morphologic change and the bone formation were assessed by HE staining and Masson staining. The result showed that rhBMP-2/PLGA/FS had overwhelming superiority in the osteogenetic ability and quality of bone defect over the control group, and it could promote the repair of bone defect and could especially repair the radial bone defect of rabbit well. It may be a promising and efficient synthetic bone graft.

  20. Orthodontic spring guidance of bilateral mandibular distraction in rabbits.

    PubMed

    Yen, S L; Shang, W; Shuler, C; Yamashita, D D

    2001-10-01

    Although distraction osteogenesis can lengthen congenitally small mandibles, the distraction procedure can be difficult to control. To study the efficacy and safety of orthodontic spring guidance on bilateral mandibular distraction, an 8-mm anterior open bite was experimentally produced and corrected during bilateral mandibular distraction in rabbits. Orthodontic springs were attached to the anterior maxilla and mandible to redirect an ongoing distraction procedure. Sixteen rabbits underwent mandibular distraction: 6 rabbits received heavy springs (8 oz), 6 rabbits received light force springs (2 oz), and 4 rabbits served as control animals with anterior open bites without spring guidance. Nickel-titanium springs were applied during the last week of osseous distraction and the first week of consolidation. Distractors were left in place throughout a 2-month consolidation period. None of the animals developed fibrous union as a result of spring guidance. The 8-mm open bite did not close in the control group or in the light spring group after 2 weeks of spring wear or during the consolidation period. Heavy springs completely closed the experimental open bites within 2 weeks (P <.01, analysis of variance). Bite corrections did not change during the consolidation period. This study indicated that the addition of an orthodontic spring to a mandibular distraction procedure did not impair bone healing. With the distraction device in place, heavy spring forces redirected an ongoing mandibular distraction procedure and corrected an open bite, distraction side effect. Direct measurements, radiographic measurements, and tissue histologic factors described changes in segment position and shape of the distraction site.

  1. Intrinsic connectivity of neural networks in the awake rabbit.

    PubMed

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

    2016-04-01

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

  2. Diagnosis and management of atherosclerotic cardiovascular disease in chronic kidney disease: a review.

    PubMed

    Mathew, Roy O; Bangalore, Sripal; Lavelle, Michael P; Pellikka, Patricia A; Sidhu, Mandeep S; Boden, William E; Asif, Arif

    2016-12-28

    Patients with chronic kidney disease (CKD) have a high prevalence of atherosclerotic cardiovascular disease, likely reflecting the presence of traditional risk factors. A greater distinguishing feature of atherosclerotic cardiovascular disease in CKD is the severity of the disease, which is reflective of an increase in inflammatory mediators and vascular calcification secondary to hyperparathyroidism of renal origin that are unique to patients with CKD. Additional components of atherosclerotic cardiovascular disease that are prominent in patients with CKD include microvascular disease and myocardial fibrosis. Therapeutic interventions that minimize cardiovascular events related to atherosclerotic cardiovascular disease in patients with CKD, as determined by well-designed clinical trials, are limited to statins. Data are lacking regarding other available therapeutic measures primarily due to exclusion of patients with CKD from major trials studying cardiovascular disease. Data from well-designed randomized controlled trials are needed to guide clinicians who care for this high-risk population in the management of atherosclerotic cardiovascular disease to improve clinical outcomes.

  3. Complications during renal artery stent placement for atherosclerotic ostial stenosis

    SciTech Connect

    Beek, Frederik J. A.; Kaatee, Robert; Beutler, Jaap J.; Ven, Peter J. van der; Mali, Willem P. T. M.

    1997-05-15

    Purpose. To describe short-term complications during stent placement for atherosclerotic renal artery ostial stenosis. Methods. Sixty-one arteries in 50 patients were treated with Palmaz stents. Nineteen patients had a single functioning kidney, 23 had a bilateral stenosis, which was stented bilaterally in 11, and 8 had a unilateral stenosis. The complications were grouped as those related to the catheterization procedure, those related to stent placement, and those possibly related to either category. The complications were divided into those with severe clinical significance (SCS), those with minor clinical significance (MCS), and radiological-technical complications (RTC). The stent placement procedures were ordered chronologically according to examination date and the complications were tabulated per group of 10 patients. Results. Five (10%) SCS, 5 (10%) MCS, and 8 (16%) RTC occurred in 50 patients. The catheterization procedure led to 2 SCS, 3 MCS, and 1 RTC. Stent placement gave rise to 7 RTC. Three SCS and 2 MCS could have been related to either catheterization or stent placement. More SCS occurred in the first group of 10 patients than in the following groups. Conclusion. Renal artery stent placement for atherosclerotic ostial stenosis has a considerable complication rate and a learning curve is present. The complications related to the actual stent placement were without clinical consequences.

  4. Imaging of the Fibrous Cap in Atherosclerotic Carotid Plaque

    SciTech Connect

    Saba, Luca; Potters, Fons; Lugt, Aad van der; Mallarini, Giorgio

    2010-08-15

    In the last two decades, a substantial number of articles have been published to provide diagnostic solutions for patients with carotid atherosclerotic disease. These articles have resulted in a shift of opinion regarding the identification of stroke risk in patients with carotid atherosclerotic disease. In the recent past, the degree of carotid artery stenosis was the sole determinant for performing carotid intervention (carotid endarterectomy or carotid stenting) in these patients. We now know that the degree of stenosis is only one marker for future cerebrovascular events. If one wants to determine the risk of these events more accurately, other parameters must be taken into account; among these parameters are plaque composition, presence and state of the fibrous cap (FC), intraplaque haemorrhage, plaque ulceration, and plaque location. In particular, the FC is an important structure for the stability of the plaque, and its rupture is highly associated with a recent history of transient ischaemic attack or stroke. The subject of this review is imaging of the FC.

  5. Pea-derived vaccines demonstrate high immunogenicity and protection in rabbits against rabbit haemorrhagic disease virus.

    PubMed

    Mikschofsky, Heike; Schirrmeier, Horst; Keil, Günther M; Lange, Bodo; Polowick, Patricia L; Keller, Wilf; Broer, Inge

    2009-08-01

    Vaccines against rabbit haemorrhagic disease virus (RHDV) are commercially produced in experimentally infected rabbits. A genetically engineered and manufactured version of the major structural protein of RHDV (VP60) is considered to be an alternative approach for vaccine production. Plants have the potential to become an excellent recombinant production system, but the low expression level and insufficient immunogenic potency of plant-derived VP60 still hamper its practical use. In this study, we analysed the expression of a novel multimeric VP60-based antigen in four different plant species, including Nicotiana tabacum L., Solanum tuberosum L., Brassica napus L. and Pisum sativum L. Significant differences were detected in the expression patterns of the novel fusion antigen cholera toxin B subunit (CTB)::VP60 (ctbvp60(SEKDEL)) at the mRNA and protein levels. Pentameric CTB::VP60 molecules were only detected in N. tabacum and P. sativum, and displayed equal levels of CTB, at approximately 0.01% of total soluble protein (TSP), and traces of detectable VP60. However, strong enhancement of the CTB protein content via self-fertilization was only observed in P. sativum, where it reached up to 0.7% of TSP. In rabbits, a strong decrease in the protective vaccine dose required from 48-400 microg potato-derived VP60 [Castanon, S., Marin, M.S., Martin-Alonso, J.M., Boga, J.A., Casais, R., Humara, J.M., Ordas, R.J. and Parra, F. (1999) Immunization with potato plants expressing VP60 protein protects against rabbit hemorrhagic disease virus. J. Virol. 73, 4452-4455; Castanon, S., Martin-Alonso, J.M., Marin, M.S., Boga, J.A., Alonso, P., Parra, F. and Ordas, R.J. (2002) The effect of the promoter on expression of VP60 gene from rabbit hemorrhagic disease virus in potato plants. Plant Sci. 162, 87-95] to 0.56-0.28 microg antigenic VP60 (measured with VP60 enzyme-linked immunosorbent assay) of crude CTB::VP60 pea extracts was demonstrated. Rabbits immunized with pea-derived CTB

  6. Symptomatic Atherosclerotic Disease and Decreased Risk of Cancer-Specific Mortality

    PubMed Central

    Benito-León, Julián; de la Aleja, Jesús González; Martínez-Salio, Antonio; Louis, Elan D.; Lichtman, Judith H.; Bermejo-Pareja, Félix

    2015-01-01

    Abstract The few studies that have assessed the association between symptomatic atherosclerotic disease and risk of cancer have had conflicting results. In addition, these studies ascertained participants either from treatment settings (ie, service-based studies) or by using a records linkage system (ie, medical records of patients evaluated at clinics or hospitals) and, therefore, were prone to selection bias. Our purpose was to estimate the risk of cancer mortality in a large population-based sample of elderly people, comparing participants with symptomatic atherosclerotic disease (atherosclerotic stroke and coronary disease) to their counterparts without symptomatic atherosclerotic disease (ie, controls) in the same population. In this population-based, prospective study (Neurological Disorders of Central Spain, NEDICES), 5262 elderly community-dwelling participants with and without symptomatic atherosclerotic disease were identified and followed for a median of 12.1 years, after which the death certificates of those who died were reviewed. A total of 2701 (53.3%) of 5262 participants died, including 314 (68.6%) of 458 participants with symptomatic atherosclerotic disease and 2387 (49.7%) of 4804 controls. Cancer mortality was reported significantly less often in those with symptomatic atherosclerotic disease (15.6%) than in controls (25.6%) (P < 0.001). In an unadjusted Cox model, risk of cancer-specific mortality was decreased in participants with symptomatic atherosclerotic disease (HR = 0.74, 95% confidence interval [CI], 0.55−0.98, P = 0.04) vs. those without symptomatic atherosclerotic disease (reference group). In an adjusted Cox model, HR = 0.58; 95% CI, 0.38−0.89; P = 0.01. This population-based, prospective study suggests that there is an inverse association between symptomatic atherosclerotic disease and risk of cancer mortality. PMID:26266364

  7. Research on intraoperative iris behavior in rabbits treated with tamsulosin and finasteride

    PubMed Central

    Horvath, K; Vultur, F; Simon, V; Voidazan, S; Mühlfay, Gh

    2015-01-01

    Aim: The purpose of this study was to investigate intraoperative iris behavior during some phacoemulsification maneuvers in rabbits treated with tamsulosin or finasteride. Material and Method: An experimental study was conducted on 26 Metis male rabbits aged 1.5 - 2 years, body weight between 3.4 and 5.6 kg, divided into three groups: Group 1 - Control, 6 rabbits; Group 2 - tamsulosin, 10 rabbits; Group 3 - finasteride, 10 rabbits. Dose calculation was performed according to body surface area ratio man/rabbit, taking into account the median lethal dose LD50. Surgery study in rabbits was done over two days by the same specialist using an adapted protocol. He was not informed before or during surgeries which group the animal belonged to, the order being random with a quasi-uniform distribution. Valid results for a modified iris behavior were obtained from two steps of the procedure (cannula irrigation maneuver and irrigation-aspiration). The iris billowing was graded from 0 to 3, according to severity. Results: The risk of intraoperative iris billowing was higher in rabbits included in tamsulosin group [OR=8.33 (CI 95% 0.63-110.09)], but insignificant statistically compare with control group (p= 0.13). In rabbits treated with finasteride the risk of intraoperative iris billowing is increased compared with those without treatment [OR=11.6 (CI 95% 0.92-147.6)], but insignificant statistically (p= 0.11). Conclusion: In our research, we showed an increased risk of intraoperative iris billowing in rabbits treated with finasteride, almost similar with those obtained in rabbits treated with tamsulosin. Further experimental or clinical studies to confirm the role of finasteride in the etiology of intraoperative floppy iris syndrome in humans are needed. Hippokratia 2015, 19 (1): 20-24. PMID:26435641

  8. Histological response to ivory implanted in rabbit mandibles.

    PubMed

    Ceravolo, F J; Molinari, J A; Baumhammers

    1975-01-01

    Ivory rod implants were found to be biologically unacceptable in rabbit mandibles. Fibrous connective-tissue capsules containing numerous multinucleated giant cells formed around the implants. Resorption of the ivory was also apparent. In addition, osteoid deposition and ankylosis at the experimental sites were not evident.

  9. Developmental Toxicity Potential of Hydroxyuera, a Positive Control, in Rabbits

    DTIC Science & Technology

    1988-05-01

    developmental toxicity testing procedure for New Zealand White rabbits is a valid model for testing substances for developmental toxicity. Coppes et al...10. Wilson JG. Methods for acministering igents anci detecting malformations in experimental animls . Tn: 0>. JG, Warkany J, eds. Teratoloqy: Principles

  10. Investigation into the transplacental transmission of Encephalitozoon cuniculi in rabbits.

    PubMed

    Owen, D G; Gannon, J

    1980-01-01

    An investigation into the transmission of Encephalitozoon cuniculi was undertaken in both naturally- and experimentally-infected rabbits. Only 2 nurslings were found with rising antibody titres at 8-10 weeks of age, when infection could have been caused by environmental contamination.

  11. Experiments with unilateral bite planes in rabbits.

    PubMed

    Sergl, H G; Farmland, M

    1975-04-01

    1. Insertion of bite planes on the right mandibular lateral teeth of eight young rabbits caused load changes in the masticatory system. Eight other animals served as controls. 2. The induced changes were equilibrated during the nine-week experimental period by adapation processes. At the end of the period all teeth were in occlusion and the glenoid fossa-condylar process distance was equal on both sides. 3. The adaptation was the result of several mechanisms working together. We found changes in the alveolar region and at distant growth structures. Cranial scolioses were observed. 4. Masticatory functional loading is a factor which regulates growth in the region of the facial skeleton.

  12. Prevention and treatment of Encephalitozoon cuniculi infection in immunosuppressed rabbits with fenbendazole

    PubMed Central

    Abu-Akkada, S. S.; Oda, S. S.

    2016-01-01

    This study was conducted to evaluate the efficacy of oral administration of fenbendazole (20 mg/kg body weight) prior to and after experimental infection of immunosuppressed rabbits with Encephalitozoon cuniculi. A total of thirty rabbits were divided into five groups: NN (non-immunosuppressed; non-infected), IN (immunosuppressed; non-infected), IPI (immunosuppressed; protected-infected), ITI (immunosuppressed; treated-infected), and II (immunosuppressed; infected) groups. Fenbendazole was administered as a prophylactic for seven successive days before infection with E. cuniculi and as a treatment for four weeks initiated on the 28th day post-challenge (PC). Experimental rabbits were infected with intraperitoneal injection of 2 × 105 E. cuniculi spores. Parameters evaluated were body weight, detection of spores in urine, serum antibody assay, hematological, biochemical and histopathological changes. The IPI and ITI groups showed a significant better final bwt than the II group. Spores were detected in urine of all infected rabbits from the 28th day PC until the end of the study. The IPI group showed the least values of antibodies (IgG) compared to the ITI and II groups. Concerning histopathological changes, the intensity of the lesions was marked particularly in the II rabbits and to a lesser extent in the ITI rabbits. Noticeable improvement was found in the IPI rabbits. It could be concluded that fenbendazole was effective to some extent in protection of rabbits against E. cuniculi infection, while when administered as a therapeutic no significant effects were observed. PMID:27822234

  13. Prevention and treatment of Encephalitozoon cuniculi infection in immunosuppressed rabbits with fenbendazole.

    PubMed

    Abu-Akkada, S S; Oda, S S

    2016-01-01

    This study was conducted to evaluate the efficacy of oral administration of fenbendazole (20 mg/kg body weight) prior to and after experimental infection of immunosuppressed rabbits with Encephalitozoon cuniculi. A total of thirty rabbits were divided into five groups: NN (non-immunosuppressed; non-infected), IN (immunosuppressed; non-infected), IPI (immunosuppressed; protected-infected), ITI (immunosuppressed; treated-infected), and II (immunosuppressed; infected) groups. Fenbendazole was administered as a prophylactic for seven successive days before infection with E. cuniculi and as a treatment for four weeks initiated on the 28th day post-challenge (PC). Experimental rabbits were infected with intraperitoneal injection of 2 × 10(5)E. cuniculi spores. Parameters evaluated were body weight, detection of spores in urine, serum antibody assay, hematological, biochemical and histopathological changes. The IPI and ITI groups showed a significant better final bwt than the II group. Spores were detected in urine of all infected rabbits from the 28th day PC until the end of the study. The IPI group showed the least values of antibodies (IgG) compared to the ITI and II groups. Concerning histopathological changes, the intensity of the lesions was marked particularly in the II rabbits and to a lesser extent in the ITI rabbits. Noticeable improvement was found in the IPI rabbits. It could be concluded that fenbendazole was effective to some extent in protection of rabbits against E. cuniculi infection, while when administered as a therapeutic no significant effects were observed.

  14. The endogenous estradiol metabolite 2-methoxyestradiol reduces atherosclerotic lesion formation in female apolipoprotein E-deficient mice.

    PubMed

    Bourghardt, Johan; Bergström, Göran; Krettek, Alexandra; Sjöberg, Sara; Borén, Jan; Tivesten, Asa

    2007-09-01

    Estradiol, the major endogenous estrogen, reduces experimental atherosclerosis and metabolizes to 2-methoxyestradiol in vascular cells. Currently undergoing evaluation in clinical cancer trials, 2-methoxyestradiol potently inhibits cell proliferation independently of the classical estrogen receptors. This study examined whether 2-methoxyestradiol affects atherosclerosis development in female mice. Apolipoprotein E-deficient mice, a well-established mouse model of atherosclerosis, were ovariectomized and treated through slow-release pellets with placebo, 17beta-estradiol (6 microg/d), or 2-methoxyestradiol [6.66 microg/d (low-dose) or 66.6 microg/d (high-dose)]. After 90 d, body weight gain decreased and uterine weight increased in the high-dose but not low-dose 2-methoxyestradiol group. En face analysis showed that the fractional area of the aorta covered by atherosclerotic lesions decreased in the high-dose 2-methoxyestradiol (52%) but not in the low-dose 2-methoxyestradiol group. Total serum cholesterol levels decreased in the high- and low-dose 2-methoxyestradiol groups (19%, P < 0.05 and 21%, P = 0.062, respectively). Estradiol treatment reduced the fractional atherosclerotic lesion area (85%) and decreased cholesterol levels (42%). In conclusion, our study shows for the first time that 2-methoxyestradiol reduces atherosclerotic lesion formation in vivo. The antiatherogenic activity of an estradiol metabolite lacking estrogen receptor activating capacity may argue that trials on cardiovascular effects of hormone replacement therapy should use estradiol rather than other estrogens. Future research should define the role of 2-methoxyestradiol as a mediator of the antiatherosclerotic actions of estradiol. Furthermore, evaluation of the effects of 2-methoxyestradiol on cardiovascular disease endpoints in ongoing clinical trials is of great interest.

  15. Urethral healing in rabbits.

    PubMed

    Scherz, H C; Kaplan, G W; Boychuk, D I; Landa, H M; Haghighi, P

    1992-08-01

    We studied urethral healing in New Zealand white rabbits by histological examination after insult (urethral catheter) or injury (urethrotomy) specifically for acute and chronic inflammation, fibrosis, fistulas, squamous metaplasia, foreign body giant cells and urethral dilatation. Urethral catheterization resulted in increased inflammation and fibrosis compared to noncatheterized animals. Skin closure techniques and materials resulted in an inflammatory response that may extend to and involve the urethra. Minor differences in suture size were not an important variable but the persistence of suture material may have a role in the degree of inflammation and the formation of foreign body giant cells. Transepithelial closure techniques drag epithelial cells into subcutaneous tissues and may predispose to fistula formation.

  16. Local Effects of Human PCSK9 on the Atherosclerotic Lesion

    PubMed Central

    Giunzioni, Ilaria; Tavori, Hagai; Covarrubias, Roman; Major, Amy S.; Ding, Lei; Zhang, Youmin; DeVay, Rachel M.; Hong, Liang; Fan, Daping; Predazzi, Irene M.; Rashid, Shirya; Linton, MacRae F.; Fazio, Sergio

    2015-01-01

    Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) promotes atherosclerosis by increasing low-density lipoprotein (LDL) cholesterol levels through degradation of hepatic LDL receptors (LDLR). Studies have described the systemic effects of PCSK9 on atherosclerosis, but whether PCSK9 has local and direct effects on the plaque in unknown. To study the local effect of human PCSK9 (hPCSK9) on atherosclerotic lesion composition independently of changes in serum cholesterol levels we generated chimeric mice expressing hPCSK9 exclusively from macrophages using marrow from hPCSK9 transgenic (hPCSK9tg) mice transplanted into apoE−/− and LDLR−/− mice, which were then placed on a high fat diet for 8 wk. We further characterized the effect of hPCSK9 expression on the inflammatory responses in the spleen and by mouse peritoneal macrophages (MPM) in vitro. We found that MPM from transgenic mice express both murine (m) Pcsk9 and hPCSK9 and that the latter reduces macrophage LDLR and LRP1 surface levels. hPCSK9 was detected in serum of mice transplanted with hPCSK9tg marrow, but did not influence lipid levels or atherosclerotic lesion size. However, marrow-derived PCSK9 progressively accumulated in lesions of apoE−/− recipient mice while increasing the infiltration of Ly6Chi inflammatory monocytes by 32% compared with controls. Expression of hPCSK9 also increased CD11b and Ly6Chi positive cell numbers in spleens of apoE−/− mice. In vitro, expression of hPCSK9 in LPS-stimulated macrophages increased mRNA levels of the pro-inflammatory markers Tnf and Il1b (40% and 45%, respectively) and suppressed those of the anti-inflammatory markers Il10 and Arg1 (30% and 44%, respectively). All PCSK9 effects were LDLR-dependent as PCSK9 protein was not detected in lesions of LDLR−/− recipient mice and did not affect macrophage or splenocyte inflammation. In conclusion, PCSK9 directly increases atherosclerotic lesion inflammation in an LDLR-dependent but cholesterol

  17. Local effects of human PCSK9 on the atherosclerotic lesion.

    PubMed

    Giunzioni, Ilaria; Tavori, Hagai; Covarrubias, Roman; Major, Amy S; Ding, Lei; Zhang, Youmin; DeVay, Rachel M; Hong, Liang; Fan, Daping; Predazzi, Irene M; Rashid, Shirya; Linton, MacRae F; Fazio, Sergio

    2016-01-01

    Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes atherosclerosis by increasing low-density lipoprotein (LDL) cholesterol levels through degradation of hepatic LDL receptor (LDLR). Studies have described the systemic effects of PCSK9 on atherosclerosis, but whether PCSK9 has local and direct effects on the plaque is unknown. To study the local effect of human PCSK9 (hPCSK9) on atherosclerotic lesion composition, independently of changes in serum cholesterol levels, we generated chimeric mice expressing hPCSK9 exclusively from macrophages, using marrow from hPCSK9 transgenic (hPCSK9tg) mice transplanted into apoE(-/-) and LDLR(-/-) mice, which were then placed on a high-fat diet (HFD) for 8 weeks. We further characterized the effect of hPCSK9 expression on the inflammatory responses in the spleen and by mouse peritoneal macrophages (MPM) in vitro. We found that MPMs from transgenic mice express both murine (m) Pcsk9 and hPCSK9 and that the latter reduces macrophage LDLR and LRP1 surface levels. We detected hPCSK9 in the serum of mice transplanted with hPCSK9tg marrow, but did not influence lipid levels or atherosclerotic lesion size. However, marrow-derived PCSK9 progressively accumulated in lesions of apoE(-/-) recipient mice, while increasing the infiltration of Ly6C(hi) inflammatory monocytes by 32% compared with controls. Expression of hPCSK9 also increased CD11b- and Ly6C(hi) -positive cell numbers in spleens of apoE(-/-) mice. In vitro, expression of hPCSK9 in LPS-stimulated macrophages increased mRNA levels of the pro-inflammatory markers Tnf and Il1b (40% and 45%, respectively) and suppressed those of the anti-inflammatory markers Il10 and Arg1 (30% and 44%, respectively). All PCSK9 effects were LDLR-dependent, as PCSK9 protein was not detected in lesions of LDLR(-/-) recipient mice and did not affect macrophage or splenocyte inflammation. In conclusion, PCSK9 directly increases atherosclerotic lesion inflammation in an LDLR-dependent but

  18. Protective effect of policosanol on endothelium and intimal thickness induced by forceps in rabbits.

    PubMed

    Noa, Miríam; Más, Rosa; Lariot, Carlos

    2007-09-01

    Policosanol is a cholesterol-lowering drug isolated from sugar cane wax with concomitant antiplatelet effects that prevents lipofundin-induced atherosclerotic lesions in rabbits and rats, including foam cell formation, and also reduces foam cell formation in carrageenan-induced granulomas in rats, while it inhibits proliferation of smooth muscle cells induced in rabbit cuffed artery. This study was undertaken to determine whether policosanol prevents endothelium damage and increase in arterial wall thickness in rabbits with arterial walls damaged with a forceps. Artery forceps were placed over the central artery of the right ear of all rabbits, and each artery was injured eight times. Animals were randomly distributed into four groups: a positive control group treated with Tween 20/H2O vehicle, two groups treated with policosanol (5 and 25 mg/kg, respectively), and a group treated with aspirin (8 mg/kg). Treatments were given for 30 days. Damaged arteries were examined by light and electron (transmission and scanning) microscopy. To evaluate intimal thickening, areas of intima were measured, and a significant reduction in policosanol-treated animals was observed. The endothelial surface, studied with scanning electron microscopy, revealed several types of damage. In control group, the endothelial surface was severely damaged. De-endothelialized areas were reduced in policosanol-treated animals. Platelet adhesion to subendothelium was seen in all animals of the control group, whereas policosanol-treated groups exhibited significantly reduced platelet adhesion. Policosanol also reduced, dose-dependently, the platelet sequestration induced in the damaged vessel wall, partially preventing the reduction in platelet count. It is concluded that policosanol prevents endothelium injury and reduces significantly intimal thickness of rabbit arteries damaged with forceps.

  19. Dietary Carnosine Prevents Early Atherosclerotic Lesion Formation in ApoE-null Mice

    PubMed Central

    Barski, Oleg A.; Xie, Zhengzhi; Baba, Shahid P.; Sithu, Srinivas D.; Agarwal, Abhinav; Cai, Jian; Bhatnagar, Aruni; Srivastava, Sanjay

    2013-01-01

    Objective Atherosclerotic lesions are associated with the accumulation of reactive aldehydes derived from oxidized lipids. Although inhibition of aldehyde metabolism has been shown to exacerbate atherosclerosis and enhance the accumulation of aldehyde-modified proteins in atherosclerotic plaques, no therapeutic interventions have been devised to prevent aldehyde accumulation in atherosclerotic lesions. Approach and Results We examined the efficacy of carnosine, a naturally occurring β-alanyl-histidine dipeptide in preventing aldehyde toxicity and atherogenesis in apoE-null mice. In vitro, carnosine reacted rapidly with lipid peroxidation-derived unsaturated aldehydes. Gas chromatography mass-spectrometry analysis showed that carnosine inhibits the formation of free aldehydes - HNE and malonaldialdehyde in Cu2+-oxidized LDL. Preloading bone marrow-derived macrophages with cell-permeable carnosine analogs reduced HNE-induced apoptosis. Oral supplementation with octyl-D-carnosine decreased atherosclerotic lesion formation in aortic valves of apoE-null mice and attenuated the accumulation of protein-acrolein, protein-HHE and protein-HNE adducts in atherosclerotic lesions, while urinary excretion of aldehydes as carnosine conjugates was increased. Conclusions The results of this study suggest that carnosine inhibits atherogenesis by facilitating aldehyde removal from atherosclerotic lesions. Endogenous levels of carnosine may be important determinants of atherosclerotic lesion formation and treatment with carnosine or related peptides could be a useful therapy for the prevention or the treatment of atherosclerosis. PMID:23559625

  20. Effects of local simvastatin on periosteal distraction osteogenesis in rabbits.

    PubMed

    Kahraman, O E; Erdogan, Ö; Namli, H; Sencar, L

    2015-04-01

    Our aim was to evaluate the effect of local simvastatin on the formation of new bone using a new design of periosteal distractor. The distractors were placed between the periosteum and bone at the inferior border of the mandible of 20 New Zealand rabbits. In the first group (n=10) simvastatin was applied locally to the distraction zone. The other 10 rabbits served as controls. The formation of new bone was evaluated with digital direct radiography, computed tomography (CT), and histomorphometric analyses. New bone formed in all rabbits, but more formed in the experimental group according to histomorphometric variables. However, other measurements did not differ significantly between the groups. The new design of the periosteal distraction device was successful in causing new bone to form. Local simvastatin made no significant contribution to the procedure.

  1. The cottontail rabbits of Virginia

    USGS Publications Warehouse

    Llewellyn, L.M.; Handley, C.O.

    1945-01-01

    Five races of cottontail rabbits belonging to three species occur in Virginia. One of them, the Mearns cottontail (Sylvilagus floridanus mearnsi), is reported here for the first time. It occurs in six southwestern counties of the state, while the eastern cottontail (S. f. mallurus) occurs in the remainder of the state with the exception of Smith and Fishermans islands off the eastern coast of Cape Charles, where it is replaced by Hitchens cottontail (S. f. hitchensi). The New England cottontail (S. transitionalis) is found on the higher mountain peaks, above 3000 feet, and the swamp rabbit (S. palustris) occurs in the Dismal Swamp region of southeastern Virginia.....The height of the breeding season for the eastern cottontail in Virginia is March and April, but breeding continues through the entire year except in December and January. The average litter size based on embryo counts was 4.7. The sex ratio of 234 specimens from all parts of the state, taken mostly in the December to February period, was 53 males to 47 females. That of a group of 145 rabbits live-trapped at Blacksburg during February and Marchwas 58 males to 42 females. The figures show that males are more active than females during the winter months, and therefore are more easily taken then....In transplanting cottontails from one section of the state to another, it is recommended that only cottontails of the same race as those originally present in the region being restocked be released there....Tularemia is not a common disease among rabbits in Virginia, but the rabbit ticks are often carriers of the disease and may transmit it to rabbits. Rabbit ticks are also found to be carriers of Rocky Mountain fever and American Q. fever. After the ticks drop off the rabbits to hibernate in the ground, which is likely to occur during mid-winter in Virginia, there is relatively little danger of humans contracting tularemia by contact with rabbits. Present laws in Virginia which prohibit rabbit hunting until the

  2. Evaluation and percutaneous management of atherosclerotic peripheral vascular disease

    SciTech Connect

    Widlus, D.M.; Osterman, F.A. Jr. )

    1989-06-02

    Atherosclerotic peripheral vascular disease (PVD) of the lower extremities deprives a person of the ability to exercise to their satisfaction, later of the ability to perform the activities of their daily life, and finally of their legs themselves. Peripheral vascular disease has long been managed by the vascular surgeon utilizing endarterectomy and peripheral arterial bypass. Patient acceptance of nonsurgical, percutaneous procedures such as percutaneous transluminal balloon angioplasty (PTA) is high. Increased utilization of these procedures has led to improved techniques and adjuncts to therapy, as well as more critical review of long-term results. This article will review the evaluation and nonoperative management of PVD, with an emphasis on the newer modalities of management presently being investigated.

  3. Laser ablation of human atherosclerotic plaque without adjacent tissue injury

    NASA Technical Reports Server (NTRS)

    Grundfest, W. S.; Litvack, F.; Forrester, J. S.; Goldenberg, T.; Swan, H. J. C.

    1985-01-01

    Seventy samples of human cadaver atherosclerotic aorta were irradiated in vitro using a 308 nm xenon chloride excimer laser. Energy per pulse, pulse duration and frequency were varied. For comparison, 60 segments were also irradiated with an argon ion and an Nd:YAG laser operated in the continuous mode. Tissue was fixed in formalin, sectioned and examined microscopically. The Nd:YAG and argon ion-irradiated tissue exhibited a central crater with irregular edges and concentric zones of thermal and blast injury. In contrast, the excimer laser-irradiated tissue had narrow deep incisions with minimal or no thermal injury. These preliminary experiments indicate that the excimer laser vaporizes tissue in a manner different from that of the continuous wave Nd:YAG or argon ion laser. The sharp incision margins and minimal damage to adjacent normal tissue suggest that the excimer laser is more desirable for general surgical and intravascular uses than are the conventionally used medical lasers.

  4. Non-atherosclerotic vascular disease in the young.

    PubMed

    Camilo, Osvaldo; Goldstein, Larry B

    2005-10-01

    There are a large variety of non-atherosclerotic causes of ischemic stroke in the young. Arterial dissection, most commonly associated with non-traumatic causes, is among the most common. Both the carotid and vertebrobasilar circulations can be affected. The vasculitidies represent a rare, but potentially treatable series of conditions that can lead to stroke through diverse mechanisms. Moyamoya is a nonatherosclerotic, noninflammatory, nonamyloid vasculopathy characterized by chronic progressive stenosis or occlusion of the distal internal carotid arteries and/or proximal portions of the middle and/or anterior cerebral arteries. Moyamoya can be idiopathic (moyamoya disease) or the result of other conditions. An appreciation of the unusual causes of stroke in the young is important when considering secondary prevention measures.

  5. CD154: the atherosclerotic risk factor in rheumatoid arthritis?

    PubMed Central

    2013-01-01

    Atherosclerosis, now regarded as a chronic inflammatory disease of the arterial wall, and its clinical manifestations have increasingly been associated with rheumatoid arthritis (RA), supporting the notion that autoimmune diseases and vascular disorders share common etiological features. Indeed, evidence pertaining to this matter indicates that inflammation and its multiple components are the driving force behind the pathogenesis of these disorders. Interestingly, CD154 and its receptors have emerged as major players in the development of RA and atherosclerosis, which raises the possibility that this axis may represent an important biological link between both complications. Indeed, CD154 signaling elicits critical inflammatory responses that are common to the pathogenesis of both diseases. Here, we provide an overview of the traditional and disease-related interrelations between RA and vascular abnormalities, while focusing on CD154 as a potential mediator in the development of atherosclerotic events in RA patients. PMID:23433179

  6. The prevention and regression of atherosclerotic plaques: emerging treatments

    PubMed Central

    Kalanuria, Atul Ashok; Nyquist, Paul; Ling, Geoffrey

    2012-01-01

    Occlusive vascular diseases, such as sudden coronary syndromes, stroke, and peripheral arterial disease, are a huge burden on the health care systems of developed and developing countries. Tremendous advances have been made over the last few decades in the diagnosis and treatment of atherosclerotic diseases. Intravascular ultrasound has been able to provide detailed information of plaque anatomy and has been used in several studies to assess outcomes. The presence of atherosclerosis disrupts the normal protective mechanism provided by the endothelium and this mechanism has been implicated in the pathophysiology of coronary artery disease and stroke. Efforts are being put into the prevention of atherosclerosis, which has been shown to begin in childhood. This paper reviews the pathophysiology of atherosclerosis and discusses the current options available for the prevention and reversal of plaque formation. PMID:23049260

  7. Bilateral atherosclerotic internal carotid artery occlusion and recurrent ischaemic stroke.

    PubMed

    Amin, Osama S M

    2015-06-08

    Bilateral internal carotid artery occlusion (BICAO) is a rare disease that carries a gloomy prognosis. We report a case of a 52-year-old man who developed ischaemic infarction at the region of the right middle cerebral artery; he was found to have atherosclerotic occlusion of both internal carotid arteries on Doppler-duplex examination. He received medical treatment only. After 1 year, he developed a new infarction at the region of the left middle cerebral artery. Conventional angiography revealed bilateral occlusion of internal carotid arteries at their origin, approximately 50% stenosis of the common carotid bulbs and mild stenosis of the origin of external carotid arteries. The patient did not undergo any form of surgical revascularisation procedures and died of severe aspiration pneumonia approximately 2 months after the second stroke. BICAO portends a poor outcome and carries a risk of recurrent ischaemic events. The best management strategy for this vascular occlusion remains unclear.

  8. CANCERS DERIVING FROM THE VIRUS PAPILLOMAS OF WILD RABBITS UNDER NATURAL CONDITIONS

    PubMed Central

    Kidd, John G.; Rous, Peyton

    1940-01-01

    The naturally occurring virus papillomas of western cottontail rabbits become malignant occasionally. The cancers derive from the papilloma cells, that is to say from elements already rendered neoplastic by the virus and still infected therewith. Papillomas produced with the virus in jack rabbits and snowshoe rabbits become cancerous in the same way but much more frequently, as is the case in domestic rabbits also. To all three species the virus is foreign. The character of the cancers of the wild rabbits is described and the relation of the virus to them discussed on the basis of experimental findings. The facts support the view that the cancers result from virus variation, this in many instances being but slight. PMID:19870976

  9. Fluorescence characteristics of atherosclerotic plaque and malignant tumors

    NASA Astrophysics Data System (ADS)

    Andersson-Engels, Stefan; Baert, Luc; Berg, Roger; D'Hallewin, Marie-Ange; Johansson, Jonas; Stenram, Unne; Svanberg, Katarina; Svanberg, Sune

    1991-06-01

    Two series of investigations utilizing laser-induced fluorescence (LIF) in characterizing diseased tissue are presented. In one in vitro investigation the fluorescence from normal and atherosclerotically diseased arteries are studied. In another clinical study the fluorescence in vivo from superficial urinary bladder malignancies in patients who had received a low-dose injection of Hematoporphyrin Derivative (HpD) is investigated. Additionally, the fluorescence properties of L-tryptophan, collagen-I powder, elastin powder, nicotinamide adenine dinucleotide and (beta) -carothene were investigated and compared with the spectra from the tissue samples. A nitrogen laser (337 nm) alone or in connection with a dye laser (405 nm) was used together with an optical multichannel analyzer (OMA) to study the fluorescence spectra. The fluorescence decay characteristics of atherosclerotic plaque were examined utilizing a mode locked argon ion laser, synchronously pumping a picosecond dye laser. A fast detection system based on photon counting was employed. The fluorescence decay curves were evaluated on a PC computer allowing up to three lifetime components to be determined. A fluorescence peak at 390 nm in fibrotic plaque was identified as due to collagen fibers, while a fluorescence peak at 520 nm was connected to (beta) -carotene. The in vivo measurements of urinary bladder malignancies were performed with the optical fiber of the OMA system inserted through the biopsy channel of a cystoscope during the diagnostical procedure. The spectral recordings from urinary bladders, obtained at 337 nm and 405 nm excitation, revealed fluorescence features which can be used to demarcate tumor areas from normal mucosa. The fluorescence emission might also be useful to characterize different degrees of dysplasia.

  10. Antiatherosclerotic Effect of Canarium odontophyllum Miq. Fruit Parts in Rabbits Fed High Cholesterol Diet

    PubMed Central

    Shakirin, Faridah Hanim; Azlan, Azrina; Ismail, Amin; Amom, Zulkhairi; Yuon, Lau Cheng

    2012-01-01

    The effect of C. odontophyllum (CO) fruit parts was investigated in hypercholesterolemic rabbits. Forty-nine rabbits, which were randomly divided into seven groups of seven animals (n = 7), received a diet containing different parts of CO fruit parts for 8 weeks. The groups were as follows: (1) normal diet: NC group and (2) hypercholesterolemic diet: PC, HS (10 mg/kg/day simvastatin), HPO (20 g kg−1 oil extracted from the pulp of CO), HKO (20 g kg−1 oil extracted from the kernel of CO), HF (50 g kg−1 fullfat pulp of CO), and HD (50 g kg−1 defatted pulp of CO). Among these groups, rabbits receiving defatted pulp of CO showed the greatest cholesterol lowering effect as it had reduced plasma LDL-C, TC, and thiobarbiturate reactive substance (TBARS) levels as well as atherosclerotic plaques. The presence of high dietary fiber and antioxidants activity are potential factors contributing to the cholesterol lowering effect. Consequently, these results indicate the potential use of CO defatted pulp as a cholesterol lowering and antioxidant agent. PMID:22811751

  11. Pleiotropic effects of acarbose on atherosclerosis development in rabbits are mediated via upregulating AMPK signals

    PubMed Central

    Chan, Kuei-Chuan; Yu, Meng-Hsun; Lin, Ming-Cheng; Huang, Chien-Ning; Chung, Dai-Jung; Lee, Yi-Ju; Wu, Cheng-Hsun; Wang, Chau-Jong

    2016-01-01

    Acarbose, an α-glucosidase inhibitor, is reported to reduce the incidence of silent myocardial infarction and slow the progression of intima-media thickening in patients with glucose intolerance. Here we investigate other impacts of acarbose on atherosclerosis development and the underlying mechanisms of atherosclerosis initiation and progression in vivo and in vitro. Rabbits fed a high cholesterol diet (HCD) were treated with acarbose (2.5–5.0 mg kg−1). Immunohistochemistry was used to assess the expression of inducible nitric oxide synthase (iNOS), Ras, proliferating cell nuclear antigen (PCNA), IL-6, β-galactosidase, and p-AMPK in atherosclerotic lesions. Treatment with acarbose in HCD-fed rabbits was found to significantly reduce the severity of aortic atheroma and neointimal expression of α-actin, PCNA, IL-6, TNF-α, Ras, and β-galactosidase; to significantly increase expression of iNOS and p-AMPK, but not to affect serum levels of glucose, total cholesterol, and LDL. Western blot analysis showed acarbose dose-dependently decreased β-galactosidase and Ras expression and increased p-AMPK expression in TNF-α-treated A7r5 cells. In addition, acarbose restored p-AMPK and iNOS levels in AMPK inhibitor- and iNOS inhibitor-treated A7r5 cells, respectively. In conclusion, acarbose can pleiotropically inhibit rabbit atherosclerosis by reducing inflammation, senescence, and VSMCs proliferation/migration via upregulating AMPK signals. PMID:27924924

  12. Herbage intake regulation and growth of rabbits raised on grasslands: back to basics and looking forward.

    PubMed

    Martin, G; Duprat, A; Goby, J-P; Theau, J-P; Roinsard, A; Descombes, M; Legendre, H; Gidenne, T

    2016-10-01

    Organic agriculture is developing worldwide, and organic rabbit production has developed within this context. It entails raising rabbits in moving cages or paddocks, which enables them to graze grasslands. As organic farmers currently lack basic technical information, the objective of this article is to characterize herbage intake, feed intake and the growth rate of rabbits raised on grasslands in different environmental and management contexts (weather conditions, grassland type and complete feed supplementation). Three experiments were performed with moving cages at an experimental station. From weaning, rabbits grazed a natural grassland, a tall fescue grassland and a sainfoin grassland in experiments 1, 2 and 3, respectively. Rabbit diets were supplemented with a complete pelleted feed limited to 69 g dry matter (DM)/rabbit per day in experiment 1 and 52 g DM/rabbit per day in experiments 2 and 3. Herbage allowance and fiber, DM and protein contents, as well as rabbit intake and live weight, were measured weekly. Mean herbage DM intake per rabbit per day differed significantly (P<0.001) between experiments. It was highest in experiment 1 (78.5 g DM/day) and was 43.9 and 51.2 g DM/day in experiments 2 and 3, respectively. Herbage allowance was the most significant determinant of herbage DM intake during grazing, followed by rabbit metabolic weight (live weight0.75) and herbage protein and fiber contents. Across experiments, a 10 g DM increase in herbage allowance and a 100 g increase in rabbit metabolic weight corresponded to a mean increase of 6.8 and 9.6 g of herbage DM intake, respectively. When including complete feed, daily mean DM intakes differed significantly among experiments (P<0.001), ranging from 96.1 g DM/rabbit per day in experiment 2 to 163.6 g DM/rabbit per day in experiment 1. Metabolic weight of rabbits raised on grasslands increased linearly over time in all three experiments, yielding daily mean growth rates of 26.2, 19.2 and 28.5 g/day in

  13. [The rabbit ear model as comedogenic test. 3. Histologic and enzyme histochemical studies of the follicle and sebaceous gland epithelium].

    PubMed

    Zimmermann, R

    1990-01-01

    A strongly comedogenic mineral oil induced histologically and enzyme-histochemically detectable changes in the follicles and sebaceous gland ducts in the skin of rabbit ears. These correlate to findings concerning acne vulgaris in humans. The rabbit ear model thus appears to be suitable for experimental studies into acne vulgaris.

  14. Study of pomegranate (Punica granatum L.) peel extract containing anthocyanins on fatty streak formation in the renal arteries in hypercholesterolemic rabbits

    PubMed Central

    Sharifiyan, Fatemeh; Movahedian-Attar, Ahmad; Nili, Nafiseh; Asgary, Sedigheh

    2016-01-01

    Background: The influence of the supplementation of pomegranate peel extract containing anthocyanins on atherosclerotic plaque formation induced by hypercholesterolemia was investigated in renal arteries in rabbits. Materials and Methods: After the determination of polyphenol and anthocyanin's content of P. granatum peel hydroalcoholic extract, 30 male rabbits were randomly divided into three groups. They were fed basic diet, hypercholesterolemic diet and hypercholesterolemic diet along with P. granatum peel extract (polyphenolic content for each rabbit 1 g/kg diet) for 2 month. Blood samples were collected at the begging, middle and end of the study in order to measure lipid concentration and oxidative and antioxidative status variables, and renal arteries were taken for the assessment of atherosclerotic plaques at the end of the study. Results: The results reveal that P. granatum peel extract significantly increases serum antioxidant capacity in the extract recipient group in comparison with hypercholesterolemic control (P < 0.05). No significant differences are observed in total cholesterol, triglyceride, low-density lipoprotein, high-density lipoprotein, very low-density lipoprotein and in mean size of accumulated fatty streaks in renal arteries in the extract treatment group in comparison with hypercholesterolemic control (P > 0.05). Conclusion: The results of this study indicate that consumption of pomegranate peel extract containing anthocyanins (polyphenol content 1 g/kg diet) despite of a significant increase in serum antioxidant capacity cannot protect the kidneys from hypercholesterolemia-induced damages during the treatment period. PMID:26962510

  15. Magnetic characterization of human blood in the atherosclerotic process in coronary arteries

    NASA Astrophysics Data System (ADS)

    Janus, B.; Bućko, M. S.; Chrobak, A.; Wasilewski, J.; Zych, M.

    2011-03-01

    In the last decades there has been an increasing interest in biomagnetism—a field of biophysics concerned with the magnetic properties of living organisms. Biomagnetism focuses on the measurement of magnetic properties of biological samples in the clinical environment. Progress in this field can provide new data for the understanding of the pathomechanism of atherosclerosis and support the diagnostic options for the evaluation and treatment of atherothrombotic complications. Lyophilized human blood samples from patients with atherosclerotic lesions (calcium scoring (CS) CS>0) and without atherosclerotic lesions (CS=0) were magnetically investigated. Magnetic measurements (performed in room and low temperature) indicated significant magnetic differences between these two groups of patients. Atherosclerotic blood samples are characterized by higher concentration of ferrimagnetic particles (magnetite and/or maghemite) and significant changes in the superparamagnetic behaviour. This research presents that magnetometry, in combination with medical research can lead to a better understanding of iron physiology in the atherosclerotic process.

  16. Characterization of atherosclerotic plaque-depositions by infrared, Raman and CARS microscopy

    NASA Astrophysics Data System (ADS)

    Matthäus, Christian; Bergner, Gero; Krafft, Christoph; Dietzek, Benjamin; Romeike, Bernd F. M.; Brehm, Bernhard R.; Popp, Jürgen

    2011-07-01

    Atherosclerotic plaques are mainly composed of proteoglycans, triglycerides, cholesterol, cholesterolester and crystalline calcium. From histopathological characterizations it is known that the composition of these atherosclerotic plaques can vary to a great extent, due to different risk factors as smoking, hyperlipedemia, or genetic background ect. The individual plaque components can be spectroscopically easily identified. Furthermore, spectroscopic imaging technologies offer the possibility to study the plaque compositions in a more quantitative manner than traditional staining techniques. Here, we compare the potential of IR, Raman and CARS microscopy to characterize the constitution of atherosclerotic plaques as well as the structure of the surrounding tissue. For data analysis and image reconstruction spectral decomposition algorithms such as vertex component analysis (VCA) were introduced. The results are in good agreement with the histopathology. Aim of the study is to correlate the compositional characteristics of atherosclerotic plaques with individual disease patterns.

  17. Myocardial hydroxyproline reduced by early administration of methylprednisolone or ibuprofen to rabbits with radiation-induced heart disease

    SciTech Connect

    Reeves, W.C.; Cunningham, D.; Schwiter, E.J.; Abt, A.; Skarlatos, S.; Wood, M.A.; Whitesell, L.

    1982-05-01

    The ability of methylprednisolone (MP) and ibuprofen (IB) to reduce the severity of the late state of radiation-induced heart disease was assessed in 57 New Zealand white rabbits. Before and shortly after cardiac irradiation, 15 rabbits received i.v. MP, 30 mg/kg twice daily for 3 days, and 15 others received IB, 12.5 mg/kg twice daily for 2 days. No drug administered to 14 irradiated rabbits, and neither irradiation nor drugs were administered to 13 rabbits that served as controls. All 15 rabbits treated with MP and 13 of the 15 treated with IB lived for 100 days. Only seven of the untreated, irradiated rabbits lived that long. Longevity of each treated group of rabbits was better (p < 0.01 and 0.05) than that of the untreated, irradiated rabbits. Surviving rabbits were killed 100 days after irradiation. Pericarditis (p < 0.05) and pericardial effusion (p < 0.01) were less frequent in the treated, irradiated groups than in the untreated, irradiated rabbits. At least some rabbits in each irradiated group had microscopic evidence of myocardial fibrosis. The fibrosis was quantitated by determination of myocardial hydroxyproline concentrations (MHP). MHP concentration in the untreated, irradiated rabbits was greater than in those treated with MP (p < 0.05) or IB (p < 0.01) and in the untreated, unirradiated rabbits (p < 0.01). Early administrative of MP or IB retarded the development of myocardial fibrosis, pericarditis and pericardial effusin, and improved survival in this experimental model of radiation-induced heart disease.

  18. Myocardial hydroxyproline reduced by early administration of methylprednisolone or ibuprofen to rabbits with radiation-induced heart disease

    SciTech Connect

    Reeves, W.C.; Cunningham, D.; Schwiter, E.J.; Abt, A.; Skarlatos, S.; Wood, M.A.; Whitesell, L.

    1982-05-01

    The ability of methylprednisolone (MP) and ibuprofen (IB) to reduce the severity of the late state of radiation-induced heart disease was assessed in 57 New Zealand white rabbits. Before and shortly after cardiac irradiation, 15 rabbits received i.v. MP, 30 mg/kg twice daily for 3 days, and 15 others received IB, 12.5 mg/kg twice daily for 2 days. No drug was administered to 14 irradiated rabbits, and neither irradiation nor drugs were administered to 13 rabbits that served as controls, All 15 rabbits treated with MP and 13 of the 15 treated with IB lived for 100 days. Only seven of the untreated, irradiated rabbits lived that long. Longevity of each treated group of rabbits was better (p less than 0.01 and 0.05) than that of the untreated, irradiated rabbits. Surviving rabbits were killed 100 days after irradiation. Pericarditis (p less than 0.05) and pericardial effusion (p less than 0.01) were less frequent in the treated, irradiated groups than in the untreated, irradiated rabbits. At least some rabbits in each irradiated group had microscopic evidence of myocardial fibrosis. The fibrosis was quantitated by determination of myocardial hydroxyproline concentrations (MHP). MHP concentration in the untreated, irradiated rabbits was greater than in those treated with MP (p less than 0.05) or IB (p less than 0.01) and in the untreated, unirradiated rabbits (p less than 0.01). Early administration of MP or IB retarded the development of myocardial fibrosis, pericarditis and pericardial effusion, and improved survival in this experimental model of radiation-induced heart disease.

  19. The Alice - "Follow the White Rabbit" - parasites of farm rabbits based on coproscopy.

    PubMed

    Kornaś, Sławomir; Kowal, Jerzy; Wierzbowska, Izabela; Basiaga, Marta; Nosal, Paweł; Niedbała, Piotr

    2015-01-01

    The aim of the study, conducted in the years 2011-2013, was to determine the level of gastrointestinal parasites infection in New Zealand White rabbits, kept at the Experimental Station of the University of Agriculture in Krakow. The study showed rabbits protozoan infection with the genus Eimeria, belonging - based on the sporulation method - to the following species: E. magna, E. media, E. perforans, E. stiedae and E. irresidua. The highest prevalence of infection, as well as the intensity of oocysts output (OPG - oocysts per gram of faeces), was noted for E. magna and E. media - respectively 31.4 % (19477.3 OPG), and 40.0 % (14256.07 OPG). The infection of rabbits with Eimeria spp. differed significantly between years. With regard to oocysts output, the level of infection was strongly connected with the age of rabbits, being higher in young animals. However, the range of infection was highest among adults. Among nematodes, Passalurus ambiguus pinworm was regularly found (prevalence reached 21.9%), other species - Trichuris leporis, and Graphidium strigosum were rarely noted. The overall infection with nematodes did not differ between years. Similarly, as in the case of Eimeria older individuals were more often infected by nematodes. We observed some trends in parasite oocysts/eggs output; the protozoan oocysts were recorded more often in faecal samples collected in the evenings, whereas the nematodes eggs occurred frequently in the mornings. This situation may be related to the phenomenon of coprophagy occurring in the mammals of Lagomorpha order. The results of the study indicate that especially coccidiosis constitute permanently throughout the years an important problem in the rabbitry examined.

  20. The prevention and treatment effects of egg yolk high density lipoprotein on the formation of atherosclerosis plaque in rabbits

    PubMed Central

    Eftekhar, Shima; Parsaei, Heidar; Keshavarzi, Zakieh; Yazdi, Abbas Tabatabaei; Hadjzadeh, Mosa-Al-Reza; Rajabzadeh, Aliakbar; Malayeri, Sina Omid

    2015-01-01

    Objective(s): Atherosclerosis is the main leading cause of cardiovascular diseases. The purpose of this study was to assess the potential preventive effect of egg yolk HDL on the atherosclerosis plaque formation. Materials and Methods: Thirty rabbits were divided into five groups: A; normal diet, B; hyper-cholesterolemic diet, C; hypercholesterolemic + 400 mg/kg egg yolk HDL D; hypercholesterolemic +100 mg/kg egg yolk HDL and E; 200 mg/kg egg yolk HDL. At the end of the experiment, the lipid profiles were measured by spectrophotometric method. The histological sections of thoracic aorta also were taken and analyzed under light microscope. Results: At the end of the 2nd and the 4th weeks, there was a significant increase of cholesterol level in groups B, C, and D compared to group A (P<0.05). Following HDL treatment, triglyceride (TG) levels increased significantly versus group A and also the TG level decreased significantly in group C, D, and E versus group B (P<0.01). Egg yolk HDL significantly increased HDL-C in groups C, D, and E (P<0.01) compared to groups A and B (P<0.05). The surface area of the atherosclerotic plaque was increased significantly in group B versus group A (P<0.001). Egg yolk HDL consumption reduced the plaque size significantly (P<0.001). Conclusion: Our findings indicated that treatment with egg yolk HDL increased serum HDL-C and decreased atherosclerotic plaque size in rabbits. Thus, egg yolk HDL may be considered as an anti-atherosclerotic treatment for cardiovascular diseases. PMID:26019796

  1. Fatty acid binding protein 4 in circulating leucocytes reflects atherosclerotic lesion progression in Apoe(-/-) mice.

    PubMed

    Agardh, Hanna E; Gertow, Karl; Salvado, Dolores M; Hermansson, Andreas; van Puijvelde, Gijs H; Hansson, Göran K; n-Berne, Gabrielle Paulsso; Gabrielsen, Anders

    2013-02-01

    Discovery of novel biomarkers for atherosclerosis is important to aid in early diagnosis of pre-symptomatic patients at high risk of cardiovascular events. The aim of the present study was therefore to identify potential biomarkers in circulating cells reflecting atherosclerotic lesion progression in the vessel wall. We performed gene arrays on circulating leucocytes from atherosclerosis prone Apoe(-/-) mice with increasing ages, using C57BL/6 mice as healthy controls. We identified fatty acid binding protein 4 (FABP4) mRNA to be augmented in mice with established disease compared with young Apoe(-/-) or controls. Interestingly, the transcript FABP4 correlated significantly with lesion size, further supporting a disease associated increase. In addition, validation of our finding on protein level showed augmented FABP4 in circulating leucocytes whereas, importantly, no change could be observed in plasma. Immunofluorescence analysis demonstrated FABP4 to be present mainly in circulating neutrophils and to some extent in monocytes. Moreover, FABP4-positive neutrophils and macrophages could be identified in the subintimal space in the plaque. Using human circulating leucocytes, we confirmed the presence of FABP4 protein in neutrophils and monocytes. In conclusion, we have showed that cellular levels of FABP4 in circulating leucocytes associate with lesion development in the experimental Apoe(-/-) model. The increased expression is primarily localized to neutrophils, but also in monocytes. We have identified FABP4 in leucocytes as a potential and easy accessible biomarker of atherosclerosis which could be of future clinical relevance.

  2. Atherosclerotic plaque ultrasound video encoding, wireless transmission, and quality assessment using H.264.

    PubMed

    Panayides, A; Pattichis, M S; Pattichis, Constantinos S; Loizou, C P; Pantziaris, M; Pitsillides, Andreas

    2011-05-01

    We propose a unifying framework for efficient encoding, transmission, and quality assessment of atherosclerotic plaque ultrasound video. The approach is based on a spatially varying encoding scheme, where video-slice quantization parameters are varied as a function of diagnostic significance. Video slices are automatically set based on a segmentation algorithm. They are then encoded using a modified version of H.264/AVC flexible macroblock ordering (FMO) technique that allows variable quality slice encoding and redundant slices (RSs) for resilience over error-prone transmission channels. We evaluate our scheme on a representative collection of ten ultrasound videos of the carotid artery for packet loss rates up to 30%. Extensive simulations incorporating three FMO encoding methods, different quantization parameters, and different packet loss scenarios are investigated. Quality assessment is based on a new clinical rating system that provides independent evaluations of the different parts of the video (subjective). We also use objective video-quality assessment metrics and estimate their correlation to the clinical quality assessment of plaque type. We find that some objective quality assessment measures computed over the plaque video slices gave very good correlations to mean opinion scores (MOSs). Here, MOSs were computed using two medical experts. Experimental results show that the proposed method achieves enhanced performance in noisy environments, while at the same time achieving significant bandwidth demands reductions, providing transmission over 3G (and beyond) wireless networks.

  3. Integrated IVUS-OCT Imaging for Atherosclerotic Plaque Characterization

    PubMed Central

    Li, Xiang; Li, Jiawen; Jing, Joe; Ma, Teng; Liang, Shanshan; Zhang, Jun; Mohar, Dilbahar; Raney, Aidan; Mahon, Sari; Brenner, Matthew; Patel, Pranav; Shung, K. Kirk; Zhou, Qifa; Chen, Zhongping

    2014-01-01

    For the diagnosis of atherosclerosis, biomedical imaging techniques such as intravascular ultrasound (IVUS) and optical coherence tomography (OCT) have been developed. The combined use of IVUS and OCT is hypothesized to remarkably increase diagnostic accuracy of vulnerable plaques. We have developed an integrated IVUS-OCT imaging apparatus, which includes the integrated catheter, motor drive unit, and imaging system. The dual-function imaging catheter has the same diameter of current clinical standard. The imaging system is capable for simultaneous IVUS and OCT imaging in real time. Ex vivo and in vivo experiments on rabbits with atherosclerosis were conducted to demonstrate the feasibility and superiority of the integrated intravascular imaging modality. PMID:24771992

  4. HEREDITARY OSTEOPETROSIS OF THE RABBIT

    PubMed Central

    Pearce, Louise; Brown, Wade H.

    1948-01-01

    The manifestations and course of an hereditary disease of the rabbit are reported. The condition is present at birth and is invariably fatal, generally in the 4th and 5th weeks of age. Retardation and eventual cessation of growth with marked reduction in size are conspicuous characteristic symptoms. The condition, which first occurred in the backcross progeny of a pure bred Dutch male rabbit, is inherited. It is determined by the expression of a simple recessive unit factor, affected individuals being homozygous for the factor. Rabbits heterozygous for the factor are identified only by appropriate breeding tests. The condition is not sex-linked. The disease has a remarkable resemblance to osteopetrosis or marble bone disease of infants and children with respect to signs and general course and also, as may be stated in anticipation of later discussions (5, 6), to the characteristic abnormal condition of the skeleton. PMID:18103397

  5. Response of the rabbit VH subgroups a and y following antigenic stimulation.

    PubMed Central

    Laster, S M; Roux, K H

    1983-01-01

    In order to test the relative immune competence of a minor VH subgroup (y), the concentrations of rabbit Ig bearing the VH subgroups a and y were determined in experimentally immunized rabbits. Three groups of three rabbits each were immunized with either Micrococcus luteus, bovine serum albumin or an alloantigenic determinant (b4) of the rabbit kappa light chain. The ratios of VHy to VHa Ig in the pre-immune sera ranged from 1:8 to 1:283. In five of the nine rabbits, the VHy to VHa ratios in affinity purified antibody (Ab) closely reflected the ratios of VHy to VHa in pre-immune serum. Of the remaining four rabbits, three produced disproportionately low amounts of VHy Ab, when compared to pre-immune values, while one rabbit produced virtually no VHy Ab. Regardless of the levels of VHy and VHa Ab detected, the kinetics of Ab production by each subgroup during the course of the immune response were similar to each other. When total serum levels of the subgroups were analysed, all rabbits displayed increases (6-450%) in total serum levels of both VHa Ig and total IgG following immunization, while in eight out of nine rabbits the level of VHy Ig remained unchanged. Our observations suggest that the immune repertoire of the minor VHy subgroup is sufficiently diverse to generate VH regions which react with a variety of antigens, and in five out of nine rabbits, VHy Ab-producing clones compete well with VHa Ab-producing clones. In addition, it appears that clones of the major and minor VH subgroups, once triggered, are under similar regulatory controls with respect to specific Ab, but differ with respect to non-specific Ig production. PMID:6406361

  6. European Rabbits as Reservoir for Coxiella burnetii

    PubMed Central

    González-Barrio, David; Maio, Elisa; Vieira-Pinto, Madalena

    2015-01-01

    We studied the role of European rabbits (Oryctolagus cuniculus) as a reservoir for Coxiella burnetii in the Iberian region. High individual and population seroprevalences observed in wild and farmed rabbits, evidence of systemic infections, and vaginal shedding support the reservoir role of the European rabbit for C. burnetii. PMID:25988670

  7. Diet-induced atherosclerosis increases the release of nitrogen oxides from rabbit aorta.

    PubMed Central

    Minor, R L; Myers, P R; Guerra, R; Bates, J N; Harrison, D G

    1990-01-01

    We examined the hypothesis that impaired endothelium-dependent vasodilation in atherosclerosis is associated with decreased synthesis of nitrogen oxides by the vascular endothelium. The descending thoracic aortae of rabbits fed either normal diet, a high cholesterol diet for 2-5 wk (hypercholesterolemic, HC), or a high cholesterol diet for 6 mo (atherosclerotic, AS) were perfused in a bioassay organ chamber with physiologic buffer containing indomethacin. Despite a dramatic impairment in the vasodilator activity of endothelium-dependent relaxing factor (EDRF) released from both HC and AS aortae (assessed by bioassay), the release of nitrogen oxides (measured by chemiluminescence) from these vessels was not reduced, but markedly increased compared to NL. Thus, impaired endothelium-dependent relaxation in atherosclerosis is neither due to decreased activity of the enzyme responsible for the production of nitrogen oxides from arginine nor to arginine deficiency. Because the production of nitrogen oxides increased in response to acetylcholine in both hypercholesterolemic and atherosclerotic vessels, impairments in signal transduction are not responsible for abnormal endothelium-dependent relaxations. Impaired vasodilator activity of EDRF by cholesterol feeding may result from loss of incorporation of nitric oxide into a more potent parent compound, or accelerated degradation of EDRF. Images PMID:2254462

  8. Emergency EC-IC bypass for symptomatic atherosclerotic ischemic stroke.

    PubMed

    Horiuchi, Tetsuyoshi; Nitta, Junpei; Ishizaka, Shigetoshi; Kanaya, Kohei; Yanagawa, Takao; Hongo, Kazuhiro

    2013-10-01

    Previous studies have shown that extracranial-intracranial (EC-IC) bypass surgery has no preventive effect on subsequent ipsilateral ischemic stroke in patients with symptomatic atherosclerotic internal carotid occlusion and hemodynamic cerebral ischemia. A few studies have assessed whether an urgent EC-IC bypass surgery is an effective treatment for main trunk stenosis or occlusion in acute stage. The authors retrospectively reviewed 58 consecutive patients who underwent urgent EC-IC bypass for symptomatic internal carotid artery or the middle cerebral artery stenosis or occlusion between January 2003 and December 2011. Clinical characteristics and neuroimagings were evaluated and analyzed. Based on preoperative angiogram, responsible lesions were the internal carotid artery in 19 (32.8%) patients and the middle cerebral artery in 39 (67.2%). No hemorrhagic complication occurred. Sixty-nine percent of patients showed improvement of neurological function after surgery, and 74.1% of patients had favorable outcome. Unfavorable outcome was associated with insufficient collateral flow and new infarction after bypass surgery.

  9. Mechanical functional role of non-atherosclerotic intimal thickening.

    PubMed

    Glagov, S; Zarins, C K; Masawa, N; Xu, C P; Bassiouny, H; Giddens, D P

    1993-01-01

    Arteries adjust to alterations in wall shear stress or tensile stress by changes in diameter, wall thickness, structure and composition. The intima participates in these adaptive reactions, particularly when changes in mechanical stresses are imposed after physiologic stress levels have been established during growth. Decreased wall shear stress due to decreased flow, flow separation or complex flow patterns, or increases in tensile stress due to increases in pressure or radius stimulate non-atherosclerotic intimal proliferation. Intimal fibrocellular hypertrophy (IFH), in the form of compact fibrocellular layers resembling the media, stabilizes when the lumen diameter is reduced sufficiently or wall thickness is increased sufficiently to restore baseline wall shear or tensile stress. Reactive-adaptive intimal proliferation is not necessarily self-limiting and may continue in the form of intimal hyperplasia (IH) which is relatively matrix-free and poorly organized. If mural and intimal changes do not result in restoration of baseline wall shear and tensile stress, IH may proceed to further narrowing and stenosis. Identification of the cellular and molecular mechanisms which underly the responses which link flow to diameter, diameter and pressure to mural restructuring, and mural restructuring to intimal thickening should provide new insights into the nature of vessel adaptations in the absence or presence of atherogenesis.

  10. Paramagnetic Manganese in the Atherosclerotic Plaque of Carotid Arteries

    PubMed Central

    Chelyshev, Yury; Ignatyev, Igor; Zanochkin, Alexey; Mamin, Georgy; Sorokin, Boris; Sorokina, Alexandra; Lyapkalo, Natalya; Gizatullina, Nazima; Orlinskii, Sergei

    2016-01-01

    The search for adequate markers of atherosclerotic plaque (AP) instability in the context of assessment of the ischemic stroke risk in patients with atherosclerosis of the carotid arteries as well as for solid physical and chemical factors that are connected with the AP stability is extremely important. We investigate the inner lining of the carotid artery specimens from the male patients with atherosclerosis (27 patients, 42–64 years old) obtained during carotid endarterectomy by using different analytical tools including ultrasound angiography, X-ray analysis, immunological, histochemical analyses, and high-field (3.4 T) pulse electron paramagnetic resonance (EPR) at 94 GHz. No correlation between the stable and unstable APs in the sense of the calcification is revealed. In all of the investigated samples, the EPR spectra of manganese, namely, Mn2+ ions, are registered. Spectral and relaxation characteristics of Mn2+ ions are close to those obtained for the synthetic (nano) hydroxyapatite species but differ from each other for stable and unstable APs. This demonstrates that AP stability could be specified by the molecular organization of their hydroxyapatite components. The origin of the obtained differences and the possibility of using EPR of Mn2+ as an AP stability marker are discussed. PMID:28078287

  11. Preventing restenosis in atherosclerotic miniswine with photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Hsiang, York N.; Crespo, M. T.; To, Eleanor C.; Sobeh, Mohammed S.; Greenwald, Stephen E.; Bower, Robert D.

    1995-05-01

    The purpose of this study was to determine whether the addition of Photodynamic Therapy (PDT) using the photosensitizer Photofrin* (P*) following balloon angioplasty (BA) could prevent restenosis in an atherosclerotic animal model. Bilateral iliac atherosclerosis was created in 21 Yucatan miniswine. Six weeks later, P* 2.5 mg/kg was given IV 24 hours prior to BA (4 mm X 20 mm, 1 inflation). Following BA, swine were randomly allocated to receive PDT via a fiberoptic probe with laser energy or the same probe without laser energy. The fiberoptic probe had a 1 cm cylindrical diffusing tip and was passed co-axially through a custom catheter to ensure central location of the probe. A continuous wave argon ion-pumped dye laser tuned to 630 nm was used to provide a fluence of 100 J/cm2. Four weeks later, swine were sacrificed and vessels perfusion-fixed in-situ with glutaraldehyde and analyzed by ocular micrometry. Five occlusions occurred, all in the PDT + BA group. Percentage intimal thickness (mean +/- SD) was 51.0 +/- 29.5 in the BA group and 71.2 +/- 35.2 in the BA + PDT group (p equals 0.21). These results suggest that the addition of PDT following BA does not prevent restenosis.

  12. Multimodal spectroscopy detects features of vulnerable atherosclerotic plaque

    NASA Astrophysics Data System (ADS)

    Šćepanović, Obrad R.; Fitzmaurice, Maryann; Miller, Arnold; Kong, Chae-Ryon; Volynskaya, Zoya; Dasari, Ramachandra R.; Kramer, John R.; Feld, Michael S.

    2011-01-01

    Early detection and treatment of rupture-prone vulnerable atherosclerotic plaques is critical to reducing patient mortality associated with cardiovascular disease. The combination of reflectance, fluorescence, and Raman spectroscopy-termed multimodal spectroscopy (MMS)-provides detailed biochemical information about tissue and can detect vulnerable plaque features: thin fibrous cap (TFC), necrotic core (NC), superficial foam cells (SFC), and thrombus. Ex vivo MMS spectra are collected from 12 patients that underwent carotid endarterectomy or femoral bypass surgery. Data are collected by means of a unitary MMS optical fiber probe and a portable clinical instrument. Blinded histopathological analysis is used to assess the vulnerability of each spectrally evaluated artery lesion. Modeling of the ex vivo MMS spectra produce objective parameters that correlate with the presence of vulnerable plaque features: TFC with fluorescence parameters indicative of collagen presence; NC/SFC with a combination of diffuse reflectance β-carotene/ceroid absorption and the Raman spectral signature of lipids; and thrombus with its Raman signature. Using these parameters, suspected vulnerable plaques can be detected with a sensitivity of 96% and specificity of 72%. These encouraging results warrant the continued development of MMS as a catheter-based clinical diagnostic technique for early detection of vulnerable plaques.

  13. Primary Prevention of Atherosclerotic Cardiovascular Disease in Women

    PubMed Central

    McKibben, Rebeccah A.; Al Rifai, Mahmoud; Mathews, Lena M.; Michos, Erin D.

    2016-01-01

    Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality among women. Despite improvements in cardiovascular disease prevention efforts, there remain gaps in cardiovascular disease awareness among women, as well as age and racial disparities in ASCVD outcomes for women. Disparity also exists in the impact the traditional risk factors confer on ASCVD risk between women and men, with smoking and diabetes both resulting in stronger relative risks in women compared to men. Additionally there are risk factors that are unique to women (such as pregnancy-related factors) or that disproportionally affect women (such as auto-immune disease) where preventive efforts should be targeted. Risk assessment and management must also be sex-specific to effectively reduce cardiovascular disease and improve outcomes among women. Evidence supports the use of statin therapy for primary prevention in women at higher ASCVD risk. However, some pause should be given to prescribing aspirin therapy in women without known ASCVD, with most evidence supporting the use of aspirin for women≥65 years not at increased risk for bleeding. This review article will summarize (1) traditional and non-traditional assessments of ASCVD risk and (2) lifestyle and pharmacologic therapies for the primary prevention of ASCVD in women. PMID:28149430

  14. [Management of atherosclerotic renal-artery stenosis in 2016].

    PubMed

    Fournier, Thomas; Sens, Florence; Rouvière, Olivier; Millon, Antoine; Juillard, Laurent

    2017-02-01

    Endovascular revascularization as treatment of atherosclerotic renal-artery stenosis (aRAS) is controversial since 3 large and multicentric randomised trials (CORAL, ASTRAL, STAR) failed to prove the superiority of percutaneous transluminal renal-artery stenting (PTRAS) over medical treatment only (MT). However, considering the multiple bias of these trials, among which questionable inclusion criterias, these results must be extrapolated in clinical practice with caution. New pathophysiological data have been helping to understand why restoring blood flow does not necessarily lead to kidney function improvement. Today, the diagnostic approach must in one hand confirm the artery stenosis and on the other hand assess its severity and impact on the kidney. Therapeutic options still lie on the American guidelines published in 2006, since no study data can be reasonably used in everyday practice. However, particular sub-groups of patients who could benefit from revascularisation have been identified through recent cohort studies. Further prospective studies are needed in order to confirm the superiority of PTRAS in these populations. Meanwhile, multidisciplinary approach should be promoted, in order to provide the best treatment for each patient.

  15. Molecular Imaging of Vulnerable Atherosclerotic Plaques in Animal Models

    PubMed Central

    Gargiulo, Sara; Gramanzini, Matteo; Mancini, Marcello

    2016-01-01

    Atherosclerosis is characterized by intimal plaques of the arterial vessels that develop slowly and, in some cases, may undergo spontaneous rupture with subsequent heart attack or stroke. Currently, noninvasive diagnostic tools are inadequate to screen atherosclerotic lesions at high risk of acute complications. Therefore, the attention of the scientific community has been focused on the use of molecular imaging for identifying vulnerable plaques. Genetically engineered murine models such as ApoE−/− and ApoE−/−Fbn1C1039G+/− mice have been shown to be useful for testing new probes targeting biomarkers of relevant molecular processes for the characterization of vulnerable plaques, such as vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, intercellular adhesion molecule (ICAM)-1, P-selectin, and integrins, and for the potential development of translational tools to identify high-risk patients who could benefit from early therapeutic interventions. This review summarizes the main animal models of vulnerable plaques, with an emphasis on genetically altered mice, and the state-of-the-art preclinical molecular imaging strategies. PMID:27618031

  16. Directional spatial frequency analysis of lipid distribution in atherosclerotic plaque

    NASA Astrophysics Data System (ADS)

    Korn, Clyde; Reese, Eric; Shi, Lingyan; Alfano, Robert; Russell, Stewart

    2016-04-01

    Atherosclerosis is characterized by the growth of fibrous plaques due to the retention of cholesterol and lipids within the artery wall, which can lead to vessel occlusion and cardiac events. One way to evaluate arterial disease is to quantify the amount of lipid present in these plaques, since a higher disease burden is characterized by a higher concentration of lipid. Although therapeutic stimulation of reverse cholesterol transport to reduce cholesterol deposits in plaque has not produced significant results, this may be due to current image analysis methods which use averaging techniques to calculate the total amount of lipid in the plaque without regard to spatial distribution, thereby discarding information that may have significance in marking response to therapy. Here we use Directional Fourier Spatial Frequency (DFSF) analysis to generate a characteristic spatial frequency spectrum for atherosclerotic plaques from C57 Black 6 mice both treated and untreated with a cholesterol scavenging nanoparticle. We then use the Cauchy product of these spectra to classify the images with a support vector machine (SVM). Our results indicate that treated plaque can be distinguished from untreated plaque using this method, where no difference is seen using the spatial averaging method. This work has the potential to increase the effectiveness of current in-vivo methods of plaque detection that also use averaging methods, such as laser speckle imaging and Raman spectroscopy.

  17. Primary Prevention of Atherosclerotic Cardiovascular Disease in Women.

    PubMed

    McKibben, Rebeccah A; Al Rifai, Mahmoud; Mathews, Lena M; Michos, Erin D

    2016-01-01

    Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality among women. Despite improvements in cardiovascular disease prevention efforts, there remain gaps in cardiovascular disease awareness among women, as well as age and racial disparities in ASCVD outcomes for women. Disparity also exists in the impact the traditional risk factors confer on ASCVD risk between women and men, with smoking and diabetes both resulting in stronger relative risks in women compared to men. Additionally there are risk factors that are unique to women (such as pregnancy-related factors) or that disproportionally affect women (such as auto-immune disease) where preventive efforts should be targeted. Risk assessment and management must also be sex-specific to effectively reduce cardiovascular disease and improve outcomes among women. Evidence supports the use of statin therapy for primary prevention in women at higher ASCVD risk. However, some pause should be given to prescribing aspirin therapy in women without known ASCVD, with most evidence supporting the use of aspirin for women≥65 years not at increased risk for bleeding. This review article will summarize (1) traditional and non-traditional assessments of ASCVD risk and (2) lifestyle and pharmacologic therapies for the primary prevention of ASCVD in women.

  18. Transgenic Rabbits Expressing Ovine PrP Are Susceptible to Scrapie

    PubMed Central

    Sarradin, Pierre; Viglietta, Céline; Limouzin, Claude; Andréoletti, Olivier; Daniel-Carlier, Nathalie; Barc, Céline; Leroux-Coyau, Mathieu; Berthon, Patricia; Chapuis, Jérôme; Rossignol, Christelle; Gatti, Jean-Luc; Belghazi, Maya; Labas, Valérie; Vilotte, Jean-Luc; Béringue, Vincent; Lantier, Frédéric; Laude, Hubert; Houdebine, Louis-Marie

    2015-01-01

    Transmissible spongiform encephalopathies (TSEs) are a group of neurodegenerative diseases affecting a wide range of mammalian species. They are caused by prions, a proteinaceous pathogen essentially composed of PrPSc, an abnormal isoform of the host encoded cellular prion protein PrPC. Constrained steric interactions between PrPSc and PrPC are thought to provide prions with species specificity, and to control cross-species transmission into other host populations, including humans. Transgenetic expression of foreign PrP genes has been successfully and widely used to overcome the recognized resistance of mouse to foreign TSE sources. Rabbit is one of the species that exhibit a pronounced resistance to TSEs. Most attempts to infect experimentally rabbit have failed, except after inoculation with cell-free generated rabbit prions. To gain insights on the molecular determinants of the relative resistance of rabbits to prions, we generated transgenic rabbits expressing the susceptible V136R154Q171 allele of the ovine PRNP gene on a rabbit wild type PRNP New Zealand background and assessed their experimental susceptibility to scrapie prions. All transgenic animals developed a typical TSE 6–8 months after intracerebral inoculation, whereas wild type rabbits remained healthy more than 700 days after inoculation. Despite the endogenous presence of rabbit PrPC, only ovine PrPSc was detectable in the brains of diseased animals. Collectively these data indicate that the low susceptibility of rabbits to prion infection is not enciphered within their non-PrP genetic background. PMID:26248157

  19. Effects of OsteoKing on osteoporotic rabbits.

    PubMed

    Dai, Lifen; Wu, Haiying; Yu, Shan; Zhao, Hongbin; Xue, Lanjie; Xu, Ming; Shen, Zhiqiang; Hu, Min

    2015-07-01

    Heng-Gu-Gu-Shang-Yu-He-Ji, also known as OsteoKing, is used as a herbal Traditional Chinese Medicine for the treatment of bone disease, including femoral head necrosis and osteoarthritis. However, whether OsteoKing has anti-osteoporotic properties has remained to be elucidated. The purpose of the present study was therefore to investigate the effects of OsteoKing on ovariectomy-induced osteoporosis in rabbits. Female New Zealand white rabbits were randomly divided into an ovariectomized (OVX) group and a sham-surgery group. The rabbits in the OVX group were subjected to an ovariectomy, while the rabbits in the sham group were subjected to the removal of an area of fat near the two ovaries. Bone mineral density, mechanical properties, serum biochemical parameters and micro-architecture were examined at 150 days post-OVX to characterize the experimental animal model. Once the osteoporotic rabbit model had been established, the rabbits in the OVX group were divided into the following groups: Model group, nilestriol group and 300 and 600 mg/kg OsteoKing groups, containing 16 rabbits in each group. OsteoKing and nilestriol were administered orally. The bone mineral density, mechanical properties, serum biochemical parameters, histology and micro-architecture were examined using dual-energy X-ray absorptiometric analysis, mechanical assessments, enzyme-linked immunosorbent assays, histopathological evaluation and micro-computerized tomography examination following 60 days and 120 days of treatment, respectively. Treatment with OsteoKing led to an elevation in the bone mineral density of the vertebra and serum phosphorus levels, reduced serum concentrations of osteocalcin, procollagen type I N-terminal peptide, tartrate-resistant acid phosphatase 5b and cross-linked N-telopeptide of type I collagen, improved mechanical properties (maximum load, stiffness and energy absorption capacity), and micro-architecture of the lumbar vertebra in the OVX osteoporotic rabbit model

  20. High density lipoprotein plasma fractions inhibit aortic fatty streaks in cholesterol-fed rabbits.

    PubMed

    Badimon, J J; Badimon, L; Galvez, A; Dische, R; Fuster, V

    1989-03-01

    The effects of in vivo administration of high density lipoprotein-very high density lipoprotein (HDL-VHDL) on the development of aortic fatty streaks were studied in cholesterol-fed rabbits. The rabbits received a 0.5% cholesterol-rich diet for 8 weeks. During this period, the HDL-VHDL group was intravenously administered with 50 mg/week of homologous HDL-VHDL protein; the control group received normal saline (0.9% NaCl). HDL-VHDL fraction was obtained at density range 1.063 to 1.25 gm/ml by ultracentrifugation of normal rabbit plasma. Along the study, plasma lipid levels followed a similar profile in both groups. At the completion of the study, atherosclerotic-like lipid-rich lesions covered 37.9 +/- 6% (X +/- SEM) of the intimal aortic surface in the control group, and 14.9 +/- 2.1% in the treated group (p less than 0.001). The values of total and free cholesterol, esterified cholesterol, and phospholipids deposited within vessel wall were significantly lower in the aortas of the HDL-VHDL treated group than those in the control group. Cholesterol accumulation in the livers was also significantly lower (p less than 0.01) in the treated group than in the control. We concluded that administration of homologous HDL-VHDL lipoprotein fraction to cholesterol-fed rabbits, dramatically inhibited the extent of aortic fatty streaks and lowered lipid deposition in the arterial wall and liver without modification of the plasma lipid levels.

  1. Modelling atherosclerosis by proteomics: Molecular changes in the ascending aortas of cholesterol-fed rabbits.

    PubMed

    Xu, Jingshu; Jüllig, Mia; Middleditch, Martin J; Cooper, Garth J S

    2015-09-01

    The cholesterol-fed rabbit is commonly used as a model to study the vascular effects of hypercholesterolemia and resulting atherosclerotic lesions. Here we undertook a proteomic case-control investigation of ascending aortas from male New Zealand White rabbits after 10 weeks on a high-cholesterol (2% w/w) diet (HCD, n = 5) or control diet (n = 5), in order to determine the changes in response to the HCD. Histology confirmed intimal thickening in the HCD group consistent with atherosclerosis, and LC-MS/MS analysis of individually-obtained ascending aortic extracts labelled with isobaric (iTRAQ) tags enabled the identification and quantitation of 453 unique proteins above the 1% false discovery rate threshold. Of 67 proteins showing significant differences in relative abundance (p < 0.05), 62 were elevated and five decreased in ascending aortas from HCD-fed rabbits compared to controls. Six proteins were selected for validation using Multiple Reaction Monitoring, which confirmed the iTRAQ results. Many of the observed protein changes are consistent with known molecular perturbations in the ascending aorta that occur in response to hypercholesterolemia, e.g. elevation of tissue levels of apolipoproteins, extracellular matrix adhesion proteins, glycolytic enzymes, heat shock proteins and proteins involved in immune defense. We also made a number of novel observations, including a 15-fold elevation of glycoprotein (trans-membrane) nmb-like (Gpnmb) in response to HCD. Gpnmb has previously been linked to angiogenesis but not to atherosclerosis. This and additional novel observations merit further investigation as these perturbations may play important and as yet undiscovered roles in the pathogenesis of atherosclerosis in rabbits as well as humans.

  2. Leukotriene B4 levels in rabbit maxillary sinusitis: limitations of the current model.

    PubMed

    Hurley, D B; Smith, G S; Vogler, G A; Desponde, Y; Citardi, M J

    2001-01-01

    Since the late 1980s, the rabbit model for sinusitis has been widely used for experimental studies on sinusitis; however, the clinical relevance of these experimental data has been questioned. To elucidate the role of leukotrienes in the pathogenesis of sinusitis, leukotriene B4 (LTB4) levels were determined in acute Streptococcus pneumoniae sinusitis in this model. The rabbit model for acute maxillary sinusitis was utilized. Briefly, the right maxillary ostium of each New Zealand white rabbit was occluded with cyanoacrylate under general anesthesia. Twenty-four hours after occlusion, the occluded sinus received an inoculation of 10(8) Streptococcus pneumoniae (ATCC 10813) or a sham inoculation of saline alone. Rabbits were then sacrificed one week later, and the maxillary sinus mucosae were harvested. Leukotriene B4 levels were determined by ELISA assay. LTB4 levels in the sinuses inoculated with bacteria tended to be higher; however, statistical analysis did not reveal significant differences between the experimental and control groups. It is possible to reliably assess leukotriene B4 levels in this model of sinusitis. Although the data suggest a trend for elevated LTB4 levels, statistical analysis did not support this conclusion. The study also demonstrated significant limitations in the current rabbit model for sinusitis; that is, the standard human sinus bacterial pathogens are minimally pathogenic in rabbit sinuses and the small size of the sinus limits the material available for assay. Further modifications of the model are necessary. After such adjustments, the role of leukotrienes in sinusitis may be further explored.

  3. Probing nanoparticle translocation across the permeable endothelium in experimental atherosclerosis.

    PubMed

    Kim, Yongtae; Lobatto, Mark E; Kawahara, Tomohiro; Lee Chung, Bomy; Mieszawska, Aneta J; Sanchez-Gaytan, Brenda L; Fay, Francois; Senders, Max L; Calcagno, Claudia; Becraft, Jacob; Tun Saung, May; Gordon, Ronald E; Stroes, Erik S G; Ma, Mingming; Farokhzad, Omid C; Fayad, Zahi A; Mulder, Willem J M; Langer, Robert

    2014-01-21

    Therapeutic and diagnostic nanomaterials are being intensely studied for several diseases, including cancer and atherosclerosis. However, the exact mechanism by which nanomedicines accumulate at targeted sites remains a topic of investigation, especially in the context of atherosclerotic disease. Models to accurately predict transvascular permeation of nanomedicines are needed to aid in design optimization. Here we show that an endothelialized microchip with controllable permeability can be used to probe nanoparticle translocation across an endothelial cell layer. To validate our in vitro model, we studied nanoparticle translocation in an in vivo rabbit model of atherosclerosis using a variety of preclinical and clinical imaging methods. Our results reveal that the translocation of lipid-polymer hybrid nanoparticles across the atherosclerotic endothelium is dependent on microvascular permeability. These results were mimicked with our microfluidic chip, demonstrating the potential utility of the model system.

  4. Probing nanoparticle translocation across the permeable endothelium in experimental atherosclerosis

    PubMed Central

    Kim, YongTae; Lobatto, Mark E.; Kawahara, Tomohiro; Lee Chung, Bomy; Mieszawska, Aneta J.; Sanchez-Gaytan, Brenda L.; Fay, Francois; Senders, Max L.; Calcagno, Claudia; Becraft, Jacob; Tun Saung, May; Gordon, Ronald E.; Stroes, Erik S. G.; Ma, Mingming; Farokhzad, Omid C.; Fayad, Zahi A.; Mulder, Willem J. M.; Langer, Robert

    2014-01-01

    Therapeutic and diagnostic nanomaterials are being intensely studied for several diseases, including cancer and atherosclerosis. However, the exact mechanism by which nanomedicines accumulate at targeted sites remains a topic of investigation, especially in the context of atherosclerotic disease. Models to accurately predict transvascular permeation of nanomedicines are needed to aid in design optimization. Here we show that an endothelialized microchip with controllable permeability can be used to probe nanoparticle translocation across an endothelial cell layer. To validate our in vitro model, we studied nanoparticle translocation in an in vivo rabbit model of atherosclerosis using a variety of preclinical and clinical imaging methods. Our results reveal that the translocation of lipid–polymer hybrid nanoparticles across the atherosclerotic endothelium is dependent on microvascular permeability. These results were mimicked with our microfluidic chip, demonstrating the potential utility of the model system. PMID:24395808

  5. Sex differences in pressure diuresis/natriuresis in rabbits.

    PubMed

    Evans, R G; Stevenson, K M; Bergström, G; Denton, K M; Madden, A C; Gribben, R L; Weekes, S R; Anderson, W P

    2000-08-01

    We tested for sex-related differences in the pressure diuresis/natriuresis relationships in anaesthetized, renally denervated rabbits, using an extracorporeal circuit to perfuse the left kidney with the rabbit's own blood, through a series of step-wise increases in renal artery pressure (RAP) (from 65 to 130 mmHg). Urine flow, sodium excretion, and the fractional excretions of sodium and urine increased with increasing RAP, and were greater in male than in female rabbits at all levels of RAP-tested. However, these apparent sex-related differences in the acute pressure diuresis/natriuresis relationships were not reflected in alterations in chronic regulation of mean arterial pressure (MAP). Thus, in rabbits on a normal salt diet (0.85 g day(-1)), resting conscious MAP was significantly greater in males (87 +/- 3 mmHg) compared with females (77+/-1 mmHg). Chronically increasing daily salt intake to 4.98 g day(-1) for 28 days had no significant effect on resting conscious MAP in either sex. Thus, although our observations indicate sex differences, at least under the present experimental conditions, in the factors regulating extracellular fluid volume, these do not appear to have a major impact in setting the level of MAP in the long term.

  6. THE RECOVERABILITY OF VIRUS FROM PAPILLOMAS PRODUCED THEREWITH IN DOMESTIC RABBITS

    PubMed Central

    Friedewald, William F.; Kidd, John G.

    1944-01-01

    By preliminary preparation of the skin in ways that render it hyperplastic the presence of infective virus can be demonstrated in extracts of domestic rabbit papillomas which yield no growths when inoculated by the ordinary methods and which for this reason have been supposed to contain no virus. The amount of virus recovered by the method outlined in the present work, however, is small when compared with the yield obtained in most instances from comparable cottontail rabbit papillomas. The yield is greatly influenced not only by the virus strain used to produce the growths but by the individual rabbit host. Although virus has been obtained from papillomas produced in domestic rabbits by all of the virus strains tested, a total of 21 thus far, only about one-fourth of these strains are readily to be procured again from the growths they cause and the others are demonstrable only in hosts in which the conditions are favorable for reasons unknown. An experimental comparison of the capacity of suspensions of papilloma tissue from domestic and cottontail rabbits to elicit specific antibodies has shown that the titers attained are approximately proportional to the amount of infective virus demonstrable in the suspensions. The findings as a whole indicate that far less virus exists in infective or antigenic form in the papillomas of domestic rabbits than in those of cottontail rabbits. PMID:19871389

  7. Performance of growing rabbits fed increasing levels of discarded Salvia hispanica L. (chia) seed.

    PubMed

    Rodríguez-Abello, Diana; Ramírez-Avilés, Luis; Navarro-Alberto, Jorge; Zamora-Bustillos, Roberto

    2016-06-01

    This experiment was carried out to evaluate the effect of including five levels of discarded chia seed (DCS) on growth, energy, and economic efficiency in rabbits. Fifty crossbred (New Zealand × Californian) weaning rabbits, weighing 798 ± 170 g, were randomly assigned to the following treatments: 0 % (control), 10 % (Ch10), 20 % (Ch20), 30 % (Ch30), and 40 % (Ch40) of DCS. Ten unsexed rabbits were allocated to each treatment and housed individually in cages; the experimental period was 6 weeks. There were no statistically significant differences between treatments in final body weight (2050 g), body weight gain (30 g/rabbit/day), and carcass weight (1010 g); however, feed intake (91 g/rabbit/day in Ch20 vs. 80 g/rabbit/day in Ch40), feed conversion ratio (2.77 in control and Ch40 vs. 2.95 in Ch10, Ch20, and Ch30), energy conversion ratio (32 MJ/kg in Ch20 vs. 29 MJ/kg on average in control, Ch10, Ch20, Ch30, and Ch40), and economic efficiency (358 % in control vs. 433 % in Ch40) showed differences (P < 0.05) between treatments. Discarded chia seed can be included up to 40 % in growing rabbit diets without any adverse effects on growth and carcass weight, and increased economic efficiency.

  8. Hepatitis E virus infection in farmed rabbits and swine in the Eastern Chinese city Lianyungang: showing no potential interspecies transmission.

    PubMed

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

    2014-11-01

    Rabbit HEV isolated recently from farmed rabbits in China has been shown experimentally to be able to infect both cynomolgus macaques and pigs. The purpose of the present study was to investigate the extent to which cross-species transmission of rabbit HEV in farm settings is a significant factor in the spread of this zoonotic infection. Rabbit and swine feces were collected from the same area in Eastern China (Lianyungang City) and analyzed by RT-PCR. Partial genome sequencing of a 365 bp region of ORF2 from the HEV positive rabbit samples revealed that they had 92-99% sequence identity with rabbit strains (rbIM163-c1 and rbIM004) isolated from Inner Mongolia. Similarly, sequencing of a 765 bp region of ORF2 of HEV positive swine samples showed 96-98% sequence identity with genotype 4d isolates collected from patients in the Yantai and Nanjing regions of China. By contrast, the sequence identity between the rabbit and swine isolates was only 73-75%, with no molecular biological evidence of interspecies transmission having occurred. It is concluded that whilst interspecies infection with rabbit HEV can be achieved experimentally, in the field it is not a significant factor in zoonotic disease transmission at least in the area of China where this study was undertaken.

  9. Microbiological quality of rabbit meat.

    PubMed

    Rodríguez-Calleja, Jose M; Santos, Jesús A; Otero, Andrés; García-López, María-Luisa

    2004-05-01

    World rabbit meat production is estimated to be over 1 million tons, and Spain is the third largest producer. Although rabbit meat is marketed and consumed worldwide, information on microbiological quality is very scarce. Here, we report indicator organisms, spoilage flora, sensory quality, and some physicochemical traits of 24 h postmortem chilled rabbit carcasses and prepackaged rabbit meat stored chilled in air for 0 to 3 days at the retail level. The mean total bacterial count (4.01 +/- 0.48 log CFU/g) for carcasses dressed at a small abattoir by a manual process was significantly lower (P < 0.05) than that (4.96 +/- 0.90 log CFU/g) for carcasses dressed at a large abattoir in automated slaughter lines. Both groups of carcasses had mean pH values of 5.98. The dominant contaminants on carcasses from the small abattoir were Pseudomonas, lactic acid bacteria, and yeasts. These microorganisms and Brochothrix thermosphacta were dominant on carcasses from the large abattoir. On prepacked hind legs (pH 6.26 +/- 0.18) stored at -1 to +1 degree C (supermarket 1), mean aerobic mesophilic count was 5.87 +/- 1.03 log CFU/g, and the major microbial groups were Pseudomonas, yeasts, lactic acid bacteria, and B. thermosphacta. On prepacked whole carcasses (pH 6.37 +/- 0.18) displayed at -1 to +5 degrees C (supermarket 2), mean aerobic mesophilic count was 6.60 +/- 1.18 and the same microbial groups were dominant. Relative Escherichia coli incidence was supermarket 2 > large abattoir > supermarket 1 > small abattoir. Overall, low numbers of coliforms, Enterobacteriaceae, psychrotrophic clostridia, coagulase-positive staphylococci, and molds were found. Sensory scores, pH values, and L-lactic acid content differentiated fresh carcasses from retail samples. Data obtained suggest that the microflora of chilled rabbit meat are different from those found on the meat of other animals.

  10. Animal models to evaluate anti-atherosclerotic drugs.

    PubMed

    Priyadharsini, Raman P

    2015-08-01

    Atherosclerosis is a multifactorial condition characterized by endothelial injury, fatty streak deposition, and stiffening of the blood vessels. The pathogenesis is complex and mediated by adhesion molecules, inflammatory cells, and smooth muscle cells. Statins have been the major drugs in treating hypercholesterolemia for the past two decades despite little efficacy. There is an urgent need for new drugs that can replace statins or combined with statins. The preclinical studies evaluating atherosclerosis require an ideal animal model which resembles the disease condition, but there is no single animal model which mimics the disease. The animal models used are rabbits, rats, mice, hamsters, mini pigs, etc. Each animal model has its own advantages and disadvantages. The method of induction of atherosclerosis includes diet, chemical induction, mechanically induced injuries, and genetically manipulated animal models. This review mainly focuses on the various animal models, method of induction, the advantages, disadvantages, and the current perspectives with regard to preclinical studies on atherosclerosis.

  11. Optical detection of structural changes in human carotid atherosclerotic plaque

    NASA Astrophysics Data System (ADS)

    Korol, R. M.; Canham, P. B.; Finlay, H. M.; Hammond, R. R.; Quantz, M.; Ferguson, G. G.; Liu, L. Y.; Lucas, A. R.

    2005-08-01

    Background: Arterial bifurcations are commonly the sites of developing atherosclerotic plaque that lead to arterial occlusions and plaque rupture (myocardial infarctions and strokes). Laser induced fluorescence (LIF) spectroscopy provides an effective nondestructive method supplying spectral information on extracellular matrix (ECM) protein composition, specifically collagen and elastin. Purpose: To investigate regional differences in the ECM proteins -- collagen I, III and elastin in unstable plaque by analyzing data from laser-induced fluorescence spectroscopy of human carotid endarterectomy specimens. Methods: Gels of ECM protein extracts (elastin, collagen types I & III) were measured as reference spectra and internal thoracic artery segments (extra tissue from bypass surgery) were used as tissue controls. Arterial segments and the endarterectomy specimens (n=21) were cut into 5mm cross-sectional rings. Ten fluorescence spectra per sampling area were then recorded at 5 sites per ring with argon laser excitation (357nm) with a penetration depth of 200 μm. Spectra were normalized to maximum intensity and analyzed using multiple regression analysis. Tissue rings were fixed in formalin (within 3 hours of surgery), sectioned and stained with H&E or Movat's Pentachrome for histological analysis. Spectroscopy data were correlated with immunohistology (staining for elastin, collagen types I, III and IV). Results: Quantitative fluorescence for the thoracic arteries revealed a dominant elastin component on the luminal side -- confirmed with immunohistology and known artery structure. Carotid endarterectomy specimens by comparison had a significant decrease in elastin signature and increased collagen type I and III. Arterial spectra were markedly different between the thoracic and carotid specimens. There was also a significant elevation (p<0.05) of collagen type I distal to the bifurcation compared to proximal tissue in the carotid specimens. Conclusion: Fluorescence

  12. Global Overview of the Epidemiology of Atherosclerotic Cardiovascular Disease.

    PubMed

    Barquera, Simon; Pedroza-Tobías, Andrea; Medina, Catalina; Hernández-Barrera, Lucía; Bibbins-Domingo, Kirsten; Lozano, Rafael; Moran, Andrew E

    2015-07-01

    Atherosclerotic cardiovascular disease (ACD) is the leading cause of mortality worldwide. The objective of this paper is to provide an overview of the global burden of ACD and its risk factors and to discuss the main challenges and opportunities for prevention. Publicly available data from the Global Burden of Disease Study were analyzed for ischemic heart disease (IHD), ischemic stroke and ACD risk factors. Data from the WHO Global Health Observatory were used to describe prevalence of diverse cardiometabolic risk factors. World Bank Gross Domestic Product per capita (GDPc) information was used to categorize countries according to income level. Cardiovascular mortality decreased globally from 1990-2010 with important differences by GDPc; during 1990 there was a positive association between IHD mortality and GDPc. Higher-income countries had higher rates compared to those of lower-income countries. High levels of body mass index (BMI), blood pressure, glucose and cholesterol have a differential contribution to mortality by income group over time; high-income countries have been able to reduce the contribution from these risk factors in the last 20 years, whereas lower/middle income countries show an increasing trend in mortality attributable to high BMI and glucose. Although age-adjusted ACD mortality rate trends decreased globally, the absolute number of ACD deaths is increasing in part due to the growth of the population and aging, as well as to important lifestyle and food-system changes that likely attenuate gains in prevention. Population and individual level preventable causes of ACD must be aggressively and efficiently targeted in countries of lower economic development in order to reduce the growing burden of disease due to ACD.

  13. Atherosclerotic cardiovascular disease in patients with chronic inflammatory joint disorders.

    PubMed

    Agca, R; Heslinga, S C; van Halm, V P; Nurmohamed, M T

    2016-05-15

    Inflammatory joint disorders (IJD), including rheumatoid arthritis (RA), ankylosing spondylitis (ASp) and psoriatic arthritis (PsA), are prevalent conditions worldwide with a considerable burden on healthcare systems. IJD are associated with increased cardiovascular (CV) disease-related morbidity and mortality. In this review, we present an overview of the literature. Standardised mortality ratios are increased in IJD compared with the general population, that is, RA 1.3-2.3, ASp 1.6-1.9 and PsA 0.8-1.6. This premature mortality is mainly caused by atherosclerotic events. In RA, this CV risk is comparable to that in type 2 diabetes. Traditional CV risk factors are more often present and partially a consequence of changes in physical function related to the underlying IJD. Also, chronic systemic inflammation itself is an independent CV risk factor. Optimal control of disease activity with conventional synthetic, targeted synthetic and biological disease-modifying antirheumatic drugs decreases this excess risk. High-grade inflammation as well as anti-inflammatory treatment alter traditional CV risk factors, such as lipids. In view of the above-mentioned CV burden in patients with IJD, CV risk management is necessary. Presently, this CV risk management is still lacking in usual care. Patients, general practitioners, cardiologists, internists and rheumatologists need to be aware of the substantially increased CV risk in IJD and should make a combined effort to timely initiate CV risk management in accordance with prevailing guidelines together with optimal control of rheumatic disease activity. CV screening and treatment strategies need to be implemented in usual care.

  14. Multiscale investigation of USPIO nanoparticles in atherosclerotic plaques and their catabolism and storage in vivo.

    PubMed

    Maraloiu, Valentin-Adrian; Appaix, Florence; Broisat, Alexis; Le Guellec, Dominique; Teodorescu, Valentin Serban; Ghezzi, Catherine; van der Sanden, Boudewijn; Blanchin, Marie-Genevieve

    2016-01-01

    The storage and catabolism of Ultrasmall SuperParamagnetic Iron Oxide (USPIO) nanoparticles were analyzed through a multiscale approach combining Two Photon Laser Scanning Microscopy (TPLSM) and High-Resolution Transmission Electron Microscopy (HRTEM) at different times after intravenous injection in an atherosclerotic ApoE(-/-) mouse model. The atherosclerotic plaque features and the USPIO heterogeneous biodistribution were revealed down from organ's scale to subcellular level. The biotransformation of the nanoparticle iron oxide (maghemite) core into ferritin, the non-toxic form of iron storage, was demonstrated for the first time ex vivo in atherosclerotic plaques as well as in spleen, the iron storage organ. These results rely on an innovative spatial and structural investigation of USPIO's catabolism in cellular phagolysosomes. This study showed that these nanoparticles were stored as non-toxic iron compounds: maghemite oxide or ferritin, which is promising for MRI detection of atherosclerotic plaques in clinics using these USPIOs. From the Clinical Editor: Advance in nanotechnology has brought new contrast agents for clinical imaging. In this article, the authors investigated the use and biotransformation of Ultrasmall Super-paramagnetic Iron Oxide (USPIO) nanoparticles for analysis of atherosclerotic plagues in Two Photon Laser Scanning Microscopy (TPLSM) and High-Resolution Transmission Electron Microscopy (HRTEM). The biophysical data generated from this study could enable the possible use of these nanoparticles for the benefits of clinical patients.

  15. Leukocyte trafficking-associated vascular adhesion protein 1 is expressed and functionally active in atherosclerotic plaques

    PubMed Central

    Silvola, Johanna M. U.; Virtanen, Helena; Siitonen, Riikka; Hellberg, Sanna; Liljenbäck, Heidi; Metsälä, Olli; Ståhle, Mia; Saanijoki, Tiina; Käkelä, Meeri; Hakovirta, Harri; Ylä-Herttuala, Seppo; Saukko, Pekka; Jauhiainen, Matti; Veres, Tibor Z.; Jalkanen, Sirpa; Knuuti, Juhani; Saraste, Antti; Roivainen, Anne

    2016-01-01

    Given the important role of inflammation and the potential association of the leukocyte trafficking-associated adhesion molecule vascular adhesion protein 1 (VAP-1) with atherosclerosis, this study examined whether functional VAP-1 is expressed in atherosclerotic lesions and, if so, whether it could be targeted by positron emission tomography (PET). First, immunohistochemistry revealed that VAP-1 localized to endothelial cells of intra-plaque neovessels in human carotid endarterectomy samples from patients with recent ischemic symptoms. In low-density lipoprotein receptor-deficient mice expressing only apolipoprotein B100 (LDLR−/−ApoB100/100), VAP-1 was expressed on endothelial cells lining inflamed atherosclerotic lesions; normal vessel walls in aortas of C57BL/6N control mice were VAP-1-negative. Second, we discovered that the focal uptake of VAP-1 targeting sialic acid-binding immunoglobulin-like lectin 9 based PET tracer [68Ga]DOTA-Siglec-9 in atherosclerotic plaques was associated with the density of activated macrophages (r = 0.58, P = 0.022). As a final point, we found that the inhibition of VAP-1 activity with small molecule LJP1586 decreased the density of macrophages in inflamed atherosclerotic plaques in mice. Our results suggest for the first time VAP-1 as a potential imaging target for inflamed atherosclerotic plaques, and corroborate VAP-1 inhibition as a therapeutic approach in the treatment of atherosclerosis. PMID:27731409

  16. An Epizootic of Diarrhea in a Rabbit Colony. Pathology and Bacteriology

    PubMed Central

    Savage, N. L.; Sheldon, W. G.

    1973-01-01

    Thirteen adult rabbits and 15 weanling rabbits exhibiting signs of diarrhea were subjected to pathological and bacteriological examination. The lesions in 11 of the adult rabbits consisted of a cecocolitis that was characterized by edema of the gut wall, necrosis of the mucosa, and serosal hemorrhages. Also, five of these 11 rabbits exhibited liver lesions consistent with Tyzzer's disease. Lesions in the weanling rabbits were minimal with only two animals exhibiting focal necrosis of the mucosa and one animal exibiting necrosis of the mesenteric lymph nodes. All animals of each age group exhibited pneumonitis. Escherichia coli was present in high numbers (approximately 1012 organisms per g dry wt contents) in the cecum of eight of 13 adult and 12 of 15 weanling rabbits. Thirteen of these isolates were serotype O128:B12. Preliminary attempts to reproduce the disease in young adult rabbits by a series of per os inoculations of an isolate of E. coli (serotype O128:B12) plus intramuscular inoculation of prednisone resulted in the induction of diarrhea in two of four rabbits. The gross and histological lesions in these two animals were similar to those of the spontaneously occurring cases, consisting of edema of the cecal wall, necrosis of the mucosa, and serosal hemorrhages. Numerous white spots of focal necrosis occurred in the liver. No intracellular organisms resembling Tyzzer's disease agent were evident in any sections examined. Inoculation of either E. coli or prednisone alone did not induce diarrhea. Subsequent attempts to reproduce the disease by these methods were unsuccessful. In spite of this inability to repeat the experimental results, it was felt that this study indicated a possible role of E. coli in rabbit diarrhea, either as an etiological agent or as a secondary invader. ImagesFig. 1.Fig. 2. PMID:4270439

  17. Peptides derived from cardiovascular G-protein-coupled receptors induce morphological cardiomyopathic changes in immunized rabbits.

    PubMed

    Matsui, S; Fu, M L; Katsuda, S; Hayase, M; Yamaguchi, N; Teraoka, K; Kurihara, T; Takekoshi, N; Murakami, E; Hoebeke, J; Hjalmarson, A

    1997-02-01

    An experimental model of early-stage cardiomyopathy was created by immunizing rabbits for 1 year with synthetic peptides corresponding to the sequence of the second extracellular loop of either beta-adrenoceptors or M2-muscarinic receptors. Thirty male rabbits were used and divided into three groups: a control group (n = 10), a group immunized with the peptide corresponding to the beta-adrenoceptor (beta 1 group) (n = 10) and a group immunized with the peptide corresponding to the M2-muscarinic receptor (M2 group) (n = 10). If the sera from both groups of immunized rabbits high-titres of anti-peptide antibodies were found throughout the study period but not in the sera from control rabbits or in the preimmune sera of immunized rabbits. No significant cross-reaction with peptides other than those used for immunization was found. The myocardial receptor density of both immunized groups displayed a strong trend toward receptor up-regulation. This was significant in the beta 1 group but not in the M2 group. Both groups of immunized rabbits displayed significantly enlarged ventricles and thinner walls, as compared with the control group. However, in contrast to the beta 1 group, which showed enlarged cavities in both left and right ventricles, the M2 group was mainly affected in the right ventricles. Moreover, morphological examinations of the hearts of rabbits from both immunized groups demonstrated focal myofibrillar lysis, loss of myofilament, mitochondrial swelling and condensation, sarcoplasmic vacuolation, deposition of dense granules in the sarcoplasm and the myofibrils. One of the sex control rabbit hearts which were examined showed mild degenerative changes in the myocardium and scant mononuclear cell infiltration. However, when all the control rabbit hearts were examined by electron microscopy, no significant alterations were found. These results suggest that immunization by peptides, corresponding to the target sequences for anti-receptor autoantibodies in

  18. Effects of autoimmune NGF deprivation in the adult rabbit and offspring.

    PubMed

    Johnson, E M; Gorin, P D; Osborne, P A; Rydel, R E; Pearson, J

    1982-05-20

    An experimental autoimmune approach to the production of nerve growth factor deprivation, which we have previously described in the rat and guinea pig, has been applied to the rabbit. This species was chosen for study because of several potential advantages. The rabbit produces large litters and has a relatively short gestation period. More importantly, rabbits generate high titers of antibody against mouse NGF and large amounts of maternal antibody are passively transferred to the developing rabbit fetus compared to most other species, particularly the rat. The sympathetic nervous system of adult rabbit immunized against mouse NGF underwent degeneration with up to an 85% decrease in neuronal numbers in the superior cervical ganglion after 10 months of immunization, thus providing further evidence that NGF is required for the survival of mature sympathetic neurons. Despite the fact that newborn rabbits born to anti-NGF producing mothers had much higher titers of anti-NGF than did rats, the effects on the developing sympathetic and sensory nervous systems were not found to be any greater than in rats. Reductions in norepinephrine levels in the heart and spleen of adult rabbits born to anti-NGF producing mothers were greater than in small intestine. Prenatal exposure to maternal anti-NGF caused reductions (up to 70%) in the number of neurons in the dorsal root ganglia. Substance-P immunoreactivity was reduced in the substantia gelatinosa of the spinal cord of rabbit exposed to maternal anti-NGF. These changes, however, were not greater than seen in the rat. We conclude that although the rabbits offers some advantage in the study of the effects of NGF deprivation in the adult animal, it appears less well suited than the rat or guinea pig to the study of the effects of NGF deprivation on development.

  19. Inducible expression of vascular cell adhesion molecule-1 by vascular smooth muscle cells in vitro and within rabbit atheroma.

    PubMed Central

    Li, H.; Cybulsky, M. I.; Gimbrone, M. A.; Libby, P.

    1993-01-01

    Vascular cell adhesion molecule-1 (VCAM-1), a mononuclear leukocyte adhesion molecule, is expressed in cultured vascular endothelial cells activated by cytokines and is induced in rabbit aortic endothelium in vivo within 1 week after initiation of an atherogenic diet. We now demonstrate that vascular smooth muscle cells can also express VCAM-1 in rabbit atherosclerotic lesions in vivo and in response to cytokines in vitro. Immunohistochemical staining of aortas from rabbits fed a 0.3% cholesterol-containing diet revealed that a portion of smooth muscle cells within intimal foam cell-rich lesions expressed VCAM-1. The intimal VCAM-1-expressing cells localized predominantly in regions above the internal elastic lamina. These VCAM-1-positive cells had the typical spindle shape of smooth muscle cells but had reduced alpha-actin expression in comparison to normal medial smooth muscle cells, and did not bear markers for endothelium, macrophages, and T cells. In culture, rabbit aortic smooth muscle cells expressed VCAM-1 mRNA and protein in a time- and concentration-dependent fashion when exposed to interferon-gamma or Gram-negative bacterial lipopolysaccharide. Cultured human vascular smooth muscle cells also expressed VCAM-1 mRNA and protein in response to lipopolysaccharide, interferon-gamma, and interleukin-4. The monokines interleukin-1 alpha and tumor necrosis factor-alpha did not induce VCAM-1 expression in either rabbit or human vascular smooth muscle cells. Inducible VCAM-1 expression by vascular smooth muscle cells in vivo during hypercholesterolemia and in vitro in response to certain cytokines suggests a broader range of VCAM-1 functions in vascular biology than heretofore appreciated. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:7504883

  20. The influence of constitutive law choice used to characterise atherosclerotic tissue material properties on computing stress values in human carotid plaques.

    PubMed

    Teng, Zhongzhao; Yuan, Jianmin; Feng, Jiaxuan; Zhang, Yongxue; Brown, Adam J; Wang, Shuo; Lu, Qingsheng; Gillard, Jonathan H

    2015-11-05

    Calculating high stress concentration within carotid atherosclerotic plaques has been shown to be complementary to anatomical features in assessing vulnerability. Reliability of stress calculation may depend on the constitutive laws/strain energy density functions (SEDFs) used to characterize tissue material properties. Different SEDFs, including neo-Hookean, one-/two-term Ogden, Yeoh, 5-parameter Mooney-Rivlin, Demiray and modified Mooney-Rivlin, have been used to describe atherosclerotic tissue behavior. However, the capacity of SEDFs to fit experimental data and the difference in the stress calculation remains unexplored. In this study, seven SEDFs were used to fit the stress-stretch data points of media, fibrous cap, lipid and intraplaque hemorrhage/thrombus obtained from 21 human carotid plaques. Semi-analytic solution, 2D structure-only and 3D fully coupled fluid-structure interaction (FSI) analyses were used to quantify stress using different SEDFs and the related material stability examined. Results show that, except for neo-Hookean, all other six SEDFs fitted the experimental points well, with vessel stress distribution in the circumferential and radial directions being similar. 2D structural-only analysis was successful for all seven SEDFs, but 3D FSI were only possible with neo-Hookean, Demiray and modified Mooney-Rivlin models. Stresses calculated using Demiray and modified Mooney-Rivlin models were nearly identical. Further analyses indicated that the energy contours of one-/two-term Ogden and 5-parameter Mooney-Rivlin models were not strictly convex and the material stability indictors under homogeneous deformations were not always positive. In conclusion, considering the capacity in characterizing material properties and stabilities, Demiray and modified Mooney-Rivlin SEDF appear practical choices for mechanical analyses to predict the critical mechanical conditions within carotid atherosclerotic plaques.

  1. The influence of constitutive law choice used to characterise atherosclerotic tissue material properties on computing stress values in human carotid plaques

    PubMed Central

    Teng, Zhongzhao; Yuan, Jianmin; Feng, Jiaxuan; Zhang, Yongxue; Brown, Adam J.; Wang, Shuo; Lu, Qingsheng; Gillard, Jonathan H.

    2015-01-01

    Calculating high stress concentration within carotid atherosclerotic plaques has been shown to be complementary to anatomical features in assessing vulnerability. Reliability of stress calculation may depend on the constitutive laws/strain energy density functions (SEDFs) used to characterize tissue material properties. Different SEDFs, including neo-Hookean, one-/two-term Ogden, Yeoh, 5-parameter Mooney–Rivlin, Demiray and modified Mooney–Rivlin, have been used to describe atherosclerotic tissue behavior. However, the capacity of SEDFs to fit experimental data and the difference in the stress calculation remains unexplored. In this study, seven SEDFs were used to fit the stress–stretch data points of media, fibrous cap, lipid and intraplaque hemorrhage/thrombus obtained from 21 human carotid plaques. Semi-analytic solution, 2D structure-only and 3D fully coupled fluid-structure interaction (FSI) analyses were used to quantify stress using different SEDFs and the related material stability examined. Results show that, except for neo-Hookean, all other six SEDFs fitted the experimental points well, with vessel stress distribution in the circumferential and radial directions being similar. 2D structural-only analysis was successful for all seven SEDFs, but 3D FSI were only possible with neo-Hookean, Demiray and modified Mooney–Rivlin models. Stresses calculated using Demiray and modified Mooney–Rivlin models were nearly identical. Further analyses indicated that the energy contours of one-/two-term Ogden and 5-parameter Mooney–Rivlin models were not strictly convex and the material stability indictors under homogeneous deformations were not always positive. In conclusion, considering the capacity in characterizing material properties and stabilities, Demiray and modified Mooney–Rivlin SEDF appear practical choices for mechanical analyses to predict the critical mechanical conditions within carotid atherosclerotic plaques. PMID:26472305

  2. Layer-specific damage experiments and modeling of human thoracic and abdominal aortas with non-atherosclerotic intimal thickening.

    PubMed

    Weisbecker, Hannah; Pierce, David M; Regitnig, Peter; Holzapfel, Gerhard A

    2012-08-01

    Many treatments for cardiovascular diseases include an endovascular insertion of stents or stent grafts into arteries, a procedure which may cause high tissue stresses and even damage in the arterial wall. In order to study such problems by using finite element methods, both appropriate constitutive models and experimental data on human tissue samples are required. Layer-specific experimental data for human tissue tested up to the supra-physiological loading range are rare in the literature. In this study, intact and layer-separated experimental data from uniaxial extension tests are presented for human thoracic and abdominal aortas with non-atherosclerotic intimal thickening undergoing supra-physiological loading. A novel pseudo-elastic damage model, proposed to describe discontinuous softening in aortic arterial tissues, is fit to the obtained experimental data. Fitting of the model with and without consideration of damage accumulation in the non-collagenous matrix material reveals that tissue damage is primarily related to the collagen fiber fabric. By employing the fit model, the effect of aortic tissue pre-conditioning on the material parameters from the resulting data fits is evaluated. Histological examination of the collagen fibers under different applied stretches is used to gain more insights into the structural changes of the tissue under supra-physiological loading.

  3. Chronic miR-29 antagonism promotes favorable plaque remodeling in atherosclerotic mice.

    PubMed

    Ulrich, Victoria; Rotllan, Noemi; Araldi, Elisa; Luciano, Amelia; Skroblin, Philipp; Abonnenc, Mélanie; Perrotta, Paola; Yin, Xiaoke; Bauer, Ashley; Leslie, Kristen L; Zhang, Pei; Aryal, Binod; Montgomery, Rusty L; Thum, Thomas; Martin, Kathleen; Suarez, Yajaira; Mayr, Manuel; Fernandez-Hernando, Carlos; Sessa, William C

    2016-06-01

    Abnormal remodeling of atherosclerotic plaques can lead to rupture, acute myocardial infarction, and death. Enhancement of plaque extracellular matrix (ECM) may improve plaque morphology and stabilize lesions. Here, we demonstrate that chronic administration of LNA-miR-29 into an atherosclerotic mouse model improves indices of plaque morphology. This occurs due to upregulation of miR-29 target genes of the ECM (col1A and col3A) resulting in reduced lesion size, enhanced fibrous cap thickness, and reduced necrotic zones. Sustained LNA-miR-29 treatment did not affect circulating lipids, blood chemistry, or ECM of solid organs including liver, lung, kidney, spleen, or heart. Collectively, these data support the idea that antagonizing miR-29 may promote beneficial plaque remodeling as an independent approach to stabilize vulnerable atherosclerotic lesions.

  4. MR histology of advanced atherosclerotic lesions of ApoE- knockout mice

    NASA Astrophysics Data System (ADS)

    Naumova, A.; Yarnykh, V.; Ferguson, M.; Rosenfeld, M.; Yuan, C.

    2016-02-01

    The purposes of this study were to examine the feasibility of determining the composition of advanced atherosclerotic plaques in fixed ApoE-knockout mice and to develop a time-efficient microimaging protocol for MR histological imaging on mice. Five formalin-fixed transgenic ApoE-knockout mice were imaged at the 9.4T Bruker BioSpec MR scanner using 3D spoiled gradient-echo sequence with an isotropic field of view of 24 mm3; TR 20.8 ms; TE 2.6 ms; flip angle 20°, resulted voxel size 47 × 63 × 94 pm3. MRI examination has shown that advanced atherosclerotic lesions of aorta, innominate and carotid arteries in ApoE-knockout mice are characterized by high calcification and presence of the large fibrofatty nodules. MRI quantification of atherosclerotic lesion components corresponded to histological assessment of plaque composition with a correlation coefficient of 0.98.

  5. Genesis and growth of extracellular vesicle-derived microcalcification in atherosclerotic plaques

    PubMed Central

    Hutcheson, Joshua D.; Goettsch, Claudia; Bertazzo, Sergio; Maldonado, Natalia; Ruiz, Jessica L.; Goh, Wilson; Yabusaki, Katsumi; Faits, Tyler; Bouten, Carlijn; Franck, Gregory; Quillard, Thibaut; Libby, Peter; Aikawa, Masanori; Weinbaum, Sheldon; Aikawa, Elena

    2015-01-01

    Clinical evidence links arterial calcification and cardiovascular risk. Finite-element modelling of the stress distribution within atherosclerotic plaques has suggested that subcellular microcalcifications in the fibrous cap may promote material failure of the plaque, but that large calcifications can stabilize it. Yet the physicochemical mechanisms underlying such mineral formation and growth in atheromata remain unknown. Here, by using three-dimensional collagen hydrogels that mimic structural features of the atherosclerotic fibrous cap, and high-resolution microscopic and spectroscopic analyses of both the hydrogels and of calcified human plaques, we demonstrate that calcific mineral formation and maturation results from a series of events involving the aggregation of calcifying extracellular vesicles, and the formation of microcalcifications and ultimately large calcification zones. We also show that calcification morphology and the plaque’s collagen content – two determinants of atherosclerotic plaque stability - are interlinked. PMID:26752654

  6. Vulnerable atherosclerotic carotid plaque evaluation by ultrasound, computed tomography angiography, and magnetic resonance imaging: an overview.

    PubMed

    Naim, Cyrille; Douziech, Maxime; Therasse, Eric; Robillard, Pierre; Giroux, Marie-France; Arsenault, Frederic; Cloutier, Guy; Soulez, Gilles

    2014-08-01

    Ischemic syndromes associated with carotid atherosclerotic disease are often related to plaque rupture. The benefit of endarterectomy for high-grade carotid stenosis in symptomatic patients has been established. However, in asymptomatic patients, the benefit of endarterectomy remains equivocal. Current research seeks to risk stratify asymptomatic patients by characterizing vulnerable, rupture-prone atherosclerotic plaques. Plaque composition, biology, and biomechanics are studied by noninvasive imaging techniques such as magnetic resonance imaging, computed tomography, ultrasound, and ultrasound elastography. These techniques are at a developmental stage and have yet to be used in clinical practice. This review will describe noninvasive techniques in ultrasound, magnetic resonance imaging, and computed tomography imaging modalities used to characterize atherosclerotic plaque, and will discuss their potential clinical applications, benefits, and drawbacks.

  7. Genesis and growth of extracellular-vesicle-derived microcalcification in atherosclerotic plaques

    NASA Astrophysics Data System (ADS)

    Hutcheson, Joshua D.; Goettsch, Claudia; Bertazzo, Sergio; Maldonado, Natalia; Ruiz, Jessica L.; Goh, Wilson; Yabusaki, Katsumi; Faits, Tyler; Bouten, Carlijn; Franck, Gregory; Quillard, Thibaut; Libby, Peter; Aikawa, Masanori; Weinbaum, Sheldon; Aikawa, Elena

    2016-03-01

    Clinical evidence links arterial calcification and cardiovascular risk. Finite-element modelling of the stress distribution within atherosclerotic plaques has suggested that subcellular microcalcifications in the fibrous cap may promote material failure of the plaque, but that large calcifications can stabilize it. Yet the physicochemical mechanisms underlying such mineral formation and growth in atheromata remain unknown. Here, by using three-dimensional collagen hydrogels that mimic structural features of the atherosclerotic fibrous cap, and high-resolution microscopic and spectroscopic analyses of both the hydrogels and of calcified human plaques, we demonstrate that calcific mineral formation and maturation results from a series of events involving the aggregation of calcifying extracellular vesicles, and the formation of microcalcifications and ultimately large calcification areas. We also show that calcification morphology and the plaque’s collagen content--two determinants of atherosclerotic plaque stability--are interlinked.

  8. [The effect of carotid endarterectomy on cognitive disturbances in patients with atherosclerotic stenosis of carotid arteries].

    PubMed

    Iakhno, N N; Fedorova, T S; Damulin, I V; Shcherbiuk, A N; Vinogradov, O A; Lavrent'ev, A V

    2011-01-01

    Clinical and neuropsychological features of non-dementia cognitive disturbances were studied in 102 patients with atherosclerotic carotid stenosis. Cognitive disturbances were assessed after the carotid endarterectomy (CEAE). Mild cognitive impairment was found in 37 (36,3%) of patients, moderate cognitive impairment was diagnosed in 36 (35,3%)patients. Moderate cognitive impairment was found more often in patients with symptomatic carotid stenosis with structural brain changes confirmed by neuroimaging data and with instable atherosclerotic plaques with the predomination of hypodensity component. It allows to suggest that both the reduction of perfusion and arterio-arterial microemboli may cause cognitive dysfunction in patients with atherosclerotic carotid stenosis. The data on the positive effect of CEAE on cognitive functions have been obtained. The positive changes were more distinct in patients with asymptomatic course of carotid stenosis. However CEAE may have a negative effect on cognitive functions in patients with moderate cognitive impairment of dysmnestic character and symptomatic carotid stenosis.

  9. Anti-atherogenic and anti-inflammatory properties of glucagon-like peptide-1, glucose-dependent insulinotropic polypepide, and dipeptidyl peptidase-4 inhibitors in experimental animals.

    PubMed

    Hirano, Tsutomu; Mori, Yusaku

    2016-04-01

    We reported that native incretins, liraglutide and dipeptidyl peptidase-4 inhibitors (DPP-4i) all confer an anti-atherosclerotic effect in apolipoprotein E-null (Apoe (-/-)) mice. We confirmed the anti-atherogenic property of incretin-related agents in the mouse wire injury model, in which the neointimal formation in the femoral artery is remarkably suppressed. Furthermore, we showed that DPP-4i substantially suppresses plaque formation in coronary arteries with a marked reduction in the accumulation of macrophages in cholesterol-fed rabbits. DPP-4i showed an anti-atherosclerotic effect in Apoe (-/-) mice mainly through the actions of glucagon-like peptide-1 and glucose-dependent insulinotropic polypepide. However, the dual incretin receptor antagonists partially attenuated the suppressive effect of DPP-4i on atherosclerosis in diabetic Apoe (-/-) mice, suggesting an incretin-independent mechanism. Exendin-4 and glucose-dependent insulinotropic polypepide elicited cyclic adenosine monophosphate generation, and suppressed the lipopolysaccharide-induced gene expression of inflammatory molecules, such as interleukin-1β, interleukin-6 and tumor necrosis factor-α, in U937 human monocytes. This suppressive effect, however, was attenuated by an inhibitor of adenylate cyclase and mimicked by 8-bromo-cyclic adenosine monophosphate or forskolin. DPP-4i substantially suppressed the lipopolysaccharide-induced expression of inflammatory cytokines without affecting cyclic adenosine monophosphate generation or cell proliferation. DPP-4i more strongly suppressed the lipopolysaccharide-induced gene expression of inflammatory molecules than incretins, most likely through inactivation of CD26. Glucagon-like peptide-1 and glucose-dependent insulinotropic polypepide suppressed oxidized low-density lipoprotein-induced macrophage foam cell formation in a receptor-dependent manner, which was associated with the downregulation of acyl-coenzyme A cholesterol acyltransferase-1 and CD36, as

  10. Immunosuppression abrogates resistance of young rabbits to Rabbit Haemorrhagic Disease (RHD).

    PubMed

    Marques, Raquel M; Teixeira, Luzia; Aguas, Artur P; Ribeiro, Joana C; Costa-e-Silva, António; Ferreira, Paula G

    2014-02-04

    Rabbit Haemorrhagic Disease (RHD) is caused by a calicivirus (RHDV) that kills 90% of infected adult European rabbits within 3 days. Remarkably, young rabbits are resistant to RHD. We induced immunosuppression in young rabbits by treatment with methylprednisolone acetate (MPA) and challenged the animals with RHDV by intramuscular injection. All of these young rabbits died within 3 days of infection due to fulminant hepatitis, presenting a large number of RHDV-positive dead or apoptotic hepatocytes, and a significant seric increase in cytokines, features that are similar to those of naïve adult rabbits infected by RHDV. We conclude that MPA-induced immunosuppression abrogates the resistance of young rabbits to RHD, indicating that there are differences in the innate immune system between young and adult rabbits that contribute to their distinct resistance/susceptibility to RHDV infection.

  11. Attenuated outward potassium currents in carotid body glomus cells of heart failure rabbit: involvement of nitric oxide

    PubMed Central

    Li, Yu-Long; Sun, Shu-Yu; Overholt, Jeffery L; Prabhakar, Nanduri R; Rozanski, George J; Zucker, Irving H; Schultz, Harold D

    2004-01-01

    It has been shown that peripheral chemoreceptor sensitivity is enhanced in both clinical and experimental heart failure (HF) and that impairment of nitric oxide (NO) production contributes to this enhancement. In order to understand the cellular mechanisms associated with the alterations of chemoreceptor function and the actions of NO in the carotid body (CB), we compared the outward K+ currents (IK) of glomus cells in sham rabbits with that in HF rabbits and monitored the effects of NO on these currents. Ik was measured in glomus cells using conventional and perforated whole-cell configurations. IK was attenuated in glomus cells of HF rabbits, and their resting membrane potentials (−34.7 ± 1.0 mV) were depolarized as compared with those in sham rabbits (−47.2 ± 1.9 mV). The selective Ca2+-dependent K+ channel (KCa) blocker iberiotoxin (IbTx, 100 nm) reduced IK in glomus cells from sham rabbits, but had no effect on IK from HF rabbits. In perforated whole-cell mode, the NO donor SNAP (100 μm) increased IK in glomus cells from HF rabbits to a greater extent than that in sham rabbits (P < 0.01), and IbTx inhibited the effects of SNAP. However, in conventional whole-cell mode, SNAP had no effect. Nω-nitro-L-arginine (L-NNA, NO synthase inhibitor) decreased Ik in sham rabbits but not in HF rabbits. The guanylate cyclase inhibitor 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ) inhibited the effect of SNAP on Ik. These results demonstrate that IK is reduced in CB glomus cells from HF rabbits. This effect is due mainly to the suppression of KCa channel activity caused by decreased availability of NO. In addition, intracellular cGMP is necessary for the KCa channel modulation by NO. PMID:14673183

  12. Bacterial Communities Associated with Atherosclerotic Plaques from Russian Individuals with Atherosclerosis

    PubMed Central

    Ziganshina, Elvira E.; Sharifullina, Dilyara M.; Lozhkin, Andrey P.; Khayrullin, Rustem N.; Ignatyev, Igor M.; Ziganshin, Ayrat M.

    2016-01-01

    Atherosclerosis is considered a chronic disease of the arterial wall and is the major cause of severe disease and death among individuals all over the world. Some recent studies have established the presence of bacteria in atherosclerotic plaque samples and suggested their possible contribution to the development of cardiovascular disease. The main objective of this preliminary pilot study was to better understand the bacterial diversity and abundance in human atherosclerotic plaques derived from common carotid arteries of individuals with atherosclerosis (Russian nationwide group) and contribute towards the further identification of a main group of atherosclerotic plaque bacteria by 454 pyrosequencing their 16S ribosomal RNA (16S rRNA) genes. The applied approach enabled the detection of bacterial DNA in all atherosclerotic plaques. We found that distinct members of the order Burkholderiales were present at high levels in all atherosclerotic plaques obtained from patients with atherosclerosis with the genus Curvibacter being predominant in all plaque samples. Moreover, unclassified Burkholderiales as well as members of the genera Propionibacterium and Ralstonia were typically the most significant taxa for all atherosclerotic plaques. Other genera such as Burkholderia, Corynebacterium and Sediminibacterium as well as unclassified Comamonadaceae, Oxalobacteraceae, Rhodospirillaceae, Bradyrhizobiaceae and Burkholderiaceae were always found but at low relative abundances of the total 16S rRNA gene population derived from all samples. Also, we found that some bacteria found in plaque samples correlated with some clinical parameters, including total cholesterol, alanine aminotransferase and fibrinogen levels. Finally, our study indicates that some bacterial agents at least partially may be involved in affecting the development of cardiovascular disease through different mechanisms. PMID:27736997

  13. Bacterial Communities Associated with Atherosclerotic Plaques from Russian Individuals with Atherosclerosis.

    PubMed

    Ziganshina, Elvira E; Sharifullina, Dilyara M; Lozhkin, Andrey P; Khayrullin, Rustem N; Ignatyev, Igor M; Ziganshin, Ayrat M

    2016-01-01

    Atherosclerosis is considered a chronic disease of the arterial wall and is the major cause of severe disease and death among individuals all over the world. Some recent studies have established the presence of bacteria in atherosclerotic plaque samples and suggested their possible contribution to the development of cardiovascular disease. The main objective of this preliminary pilot study was to better understand the bacterial diversity and abundance in human atherosclerotic plaques derived from common carotid arteries of individuals with atherosclerosis (Russian nationwide group) and contribute towards the further identification of a main group of atherosclerotic plaque bacteria by 454 pyrosequencing their 16S ribosomal RNA (16S rRNA) genes. The applied approach enabled the detection of bacterial DNA in all atherosclerotic plaques. We found that distinct members of the order Burkholderiales were present at high levels in all atherosclerotic plaques obtained from patients with atherosclerosis with the genus Curvibacter being predominant in all plaque samples. Moreover, unclassified Burkholderiales as well as members of the genera Propionibacterium and Ralstonia were typically the most significant taxa for all atherosclerotic plaques. Other genera such as Burkholderia, Corynebacterium and Sediminibacterium as well as unclassified Comamonadaceae, Oxalobacteraceae, Rhodospirillaceae, Bradyrhizobiaceae and Burkholderiaceae were always found but at low relative abundances of the total 16S rRNA gene population derived from all samples. Also, we found that some bacteria found in plaque samples correlated with some clinical parameters, including total cholesterol, alanine aminotransferase and fibrinogen levels. Finally, our study indicates that some bacterial agents at least partially may be involved in affecting the development of cardiovascular disease through different mechanisms.

  14. Chinese Herbal Cardiotonic Pill Stabilizes Vulnerable Plaques in Rabbits by Decreasing the Expression of Adhesion Molecules

    PubMed Central

    Chen, Liang; Li, Xiaonan; Li, Changjiang; Rong, Yuanyuan; Xiao, Yawei; Xu, Xinsheng; Yao, Guihua; Jiang, Guihua

    2016-01-01

    Abstract: The cardiotonic pill (CP), consisting of a mixture of Radix Salviae Miltiorrhizae, Radix Notoginseng, and Borneolum Syntheticum, has been widely used in the prevention and treatment of cardiovascular disease. Adhesion molecules, including intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1, are involved in the development of vulnerable plaque. We investigated the effect of the CP in a rabbit model of vulnerable plaque established by local transfection with p53 gene. Compared with the control group, rabbits with vulnerable plaque showed a significantly lower intima-media thickness and plaque burden after CP treatment for 12 weeks. Moreover, the reduction in rate of plaque rupture and vulnerability index was similar. On enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and immunohistochemistry analysis, the expression of intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1 was inhibited with CP treatment. CP treatment could postpone atherosclerotic plaque development and stabilize vulnerable plaque by inhibiting the expression of adhesion molecules in treatment of cardiovascular disease. PMID:27110743

  15. Histopathological Studies on Rabbits Infected by Bacteria Causing Infectious Keratitis in Human through Eye Inoculation

    PubMed Central

    Aldebasi, Yousef H.; Mohamed, Hala A.; Aly, Salah M.

    2014-01-01

    Aim This study aimed to investigate the pathogenic effect of bacteria causing infectious keratitis among patients through experimental study conducted on rabbits’ eyes with the aid of histopathology as eye infection is a common disease in developing countries that may complicate to loss of vision. Methodology 100 swab samples were collected from human infected eyes, at Qassim region during 2012, for the isolation of Pseudomonas aeruginosa and Staphylococcus aureus. The isolated pathogenic bacteria were tested to various antibiotics using some selected antibiotics discs through agar-well diffusion method. Then, experimental study conducted on 27 rabbits. The rabbits were divided randomly into three equal groups, each containing 9 rabbits. Rabbits of group (1) served as control group (Negative Control) and their eyes were inoculated with the buffer only. Rabbits of group (2) were inoculated through eyes with the isolated Pseudomonas aeruginosa. Rabbits of group (3) were inoculated through eyes with the isolated Staphylococcus aureus. Results Out of 100 collected swab samples from human infected eyes, Pseudomonas aeruginosa and Staphylococcus aureus were isolated with a total percentage of 25.21% and 15.65%; respectively and used in this study. Both bacterial isolates were sensitive to Gentamicin and Cefuroxime. Clinically, experimentally infected rabbits by Pseudomonas aeruginosa, revealed varying degree corneal abrasions, corneal abscess and dense corneal opacity. Histopathologically, at 3rd day post-infection (PI), the cornea revealed polymorpho-nuclear cells infiltration with loss of the outer epithelial lining. At 7th day PI, neutrophils were seen in the stroma. At 15th day PI, proliferation of fibroblasts and new vascularisation were seen in the stroma. Clinically, rabbits experimentally infected with Staphylococcus aureus, revealed corneal ulcers and focal abscesses. Histopathologically, at 3rd and 7th day PI, the cornea revealed edema and infiltration of

  16. Identification of chemical components of combustion emissions that affect pro-atherosclerotic vascular responses in mice

    PubMed Central

    Seilkop, Steven K.; Campen, Matthew J.; Lund, Amie K.; McDonald, Jacob D.; Mauderly, Joe L.

    2012-01-01

    Combustion emissions cause pro-atherosclerotic responses in apolipoprotein E-deficient (ApoE/−) mice, but the causal components of these complex mixtures are unresolved. In studies previously reported, ApoE−/− mice were exposed by inhalation 6 h/day for 50 consecutive days to multiple dilutions of diesel or gasoline exhaust, wood smoke, or simulated “downwind” coal emissions. In this study, the analysis of the combined four-study database using the Multiple Additive Regression Trees (MART) data mining approach to determine putative causal exposure components regardless of combustion source is reported. Over 700 physical–chemical components were grouped into 45 predictor variables. Response variables measured in aorta included endothelin-1, vascular endothelin growth factor, three matrix metalloproteinases (3, 7, 9), metalloproteinase inhibitor 2, heme-oxygenase-1, and thiobarbituric acid reactive substances. Two or three predictors typically explained most of the variation in response among the experimental groups. Overall, sulfur dioxide, ammonia, nitrogen oxides, and carbon monoxide were most highly predictive of responses, although their rankings differed among the responses. Consistent with the earlier finding that filtration of particles had little effect on responses, particulate components ranked third to seventh in predictive importance for the eight response variables. MART proved useful for identifying putative causal components, although the small number of pollution mixtures (4) can provide only suggestive evidence of causality. The potential independent causal contributions of these gases to the vascular responses, as well as possible interactions among them and other components of complex pollutant mixtures, warrant further evaluation. PMID:22486345

  17. Prevalence and risk factors for atherosclerotic carotid stenosis and plaque

    PubMed Central

    Woo, Shin Young; Joh, Jin Hyun; Han, Sang-Ah; Park, Ho-Chul

    2017-01-01

    Abstract Atherosclerotic carotid stenosis (ACS) is a major cause of ischemic stroke. Screening for asymptomatic ACS is important to identify the patients who require longitudinal surveillance, medication, or endovascular surgery. The aim of this study was to assess the prevalence and risk factors for ACS and carotid plaque (CP) in Korea using a population-based screening study. We recruited participants during visits to several community welfare centers in Korea. The baseline characteristics of the study population were collected. All patients underwent duplex ultrasonography to examine their bilateral carotid arteries. ACS was defined as the presence of plaque with ≥50% vessel diameter reduction and peak systolic velocity (PSV) ≥125 cm/s or PSV ratio ≥2.0. CP was defined as the presence of plaque with <50% vessel diameter reduction. The Mann–Whitney test, χ2 test, Fisher exact test, and logistic regression were used in the statistical analysis. A total of 3030 participants were enrolled in this study (male 43.7% and female 56.3%). The prevalence of ACS and CP was 1.1% and 5.7%, respectively. Significant risk factors for CP included age ≥80 years (odds ratio [OR], 8.11; 95% confidence interval [CI], 3.45–18.93), male sex (OR, 2.16; 95% CI, 1.29–3.61), hypertension (OR, 1.72; 95% CI, 1.21–2.45), and hyperlipidemia (OR, 1.84; 95% CI, 1.30–2.62). The presence of ACS was significantly associated with age (OR, 1.07; 95% CI, 1.03–1.12), hypertension (OR, 3.16; 95% CI, 1.34–7.46), and being an ex-smoker (OR, 6.81; 95% CI, 1.66–27.93) or current smoker (OR, 6.97; 95% CI, 1.78–27.31) after adjusting for confounding factors. This population-based screening study revealed that ACS was uncommon and had a prevalence of 1.1% in the study population. Age, hypertension, and smoking were risk factors for ACS. Further investigations into the prevalence and risk factors of ACS are required, as are studies on the cost-effectiveness of a national screening

  18. Plasma viscosity increase with progression of peripheral arterial atherosclerotic disease.

    PubMed

    Poredos, P; Zizek, B

    1996-03-01

    -macroglobulin (r=0.78, P < 0.01). These results indicate that in patients with peripheral arterial disease plasma viscosity increases with the progression of the atherosclerotic process and is correlated with the clinical stages of the disease.

  19. A case of atherosclerotic inferior mesenteric artery aneurysm secondary to high flow state.

    PubMed

    Troisi, Nicola; Esposito, Giovanni; Cefalì, Pietro; Setti, Marco

    2011-07-01

    Inferior mesenteric artery aneurysms are very rare and they are among the rarest of visceral artery aneurysms. Sometimes, the distribution of the blood flow due to chronic atherosclerotic occlusion of some arteries can establish an increased flow into a particular supplying district (high flow state). A high flow state in a stenotic inferior mesenteric artery in compensation for a mesenteric occlusive disease can produce a rare form of aneurysm. We report the case of an atherosclerotic inferior mesenteric aneurysm secondary to high flow state (association with occlusion of the celiac trunk and severe stenosis of the superior mesenteric artery), treated by open surgical approach.

  20. Specific imaging of atherosclerotic plaque lipids with two-wavelength intravascular photoacoustics

    PubMed Central

    Wu, Min; Jansen, Krista; van der Steen, Antonius F. W.; van Soest, Gijs

    2015-01-01

    The lipid content in plaques is an important marker for identifying atherosclerotic lesions and disease states. Intravascular photoacoustic (IVPA) imaging can be used to visualize lipids in the artery. In this study, we further investigated lipid detection in the 1.7-µm spectral range. By exploiting the relative difference between the IVPA signal strengths at 1718 and 1734 nm, we could successfully detect and differentiate between the plaque lipids and peri-adventitial fat in human coronary arteries ex vivo. Our study demonstrates that IVPA imaging can positively identify atherosclerotic plaques using only two wavelengths, which could enable rapid data acquisition in vivo. PMID:26417500

  1. Immunostaining of macrophages, endothelial cells and smooth muscle cells in the atherosclerotic mouse aorta

    PubMed Central

    Menon, Prashanthi; Fisher, Edward A.

    2016-01-01

    The atherosclerotic mouse aorta consists of a heterogeneous population of cells, including macrophages, endothelial cells (EC) and smooth muscle cells (SMC), that play critical roles in cardiovascular disease. Identification of these vascular cells in the vessel wall is important to understanding their function in pathological conditions. Immunohistochemistry is an invaluable technique used to detect the presence of cells in different tissues. Here, we describe immunohistochemical techniques commonly used for the detection of the vascular cells in the atherosclerotic mouse aorta using cell specific markers. PMID:26445786

  2. Renovascular heart failure: heart failure in patients with atherosclerotic renal artery disease.

    PubMed

    Kawarada, Osami; Yasuda, Satoshi; Noguchi, Teruo; Anzai, Toshihisa; Ogawa, Hisao

    2016-07-01

    Atherosclerotic renal artery disease presents with a broad spectrum of clinical features, including heart failure as well as hypertension, and renal failure. Although recent randomized controlled trials failed to demonstrate renal artery stenting can reduce blood pressure or the number of cardiovascular or renal events more so than medical therapy, increasing attention has been paid to flash pulmonary edema and congestive heart failure associated with atherosclerotic renal artery disease. This clinical entity "renovascular heart failure" is diagnosed retrospectively. Given the increasing global burden of heart failure, this review highlights the background and catheter-based therapeutic aspects for renovascular heart failure.

  3. Characterization of atherosclerotic plaques by cross-polarization optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Gubarkova, Ekaterina V.; Dudenkova, Varvara V.; Feldchtein, Felix I.; Timofeeva, Lidia B.; Kiseleva, Elena B.; Kuznetsov, Sergei S.; Moiseev, Alexander A.; Gelikonov, Gregory V.; Vitkin, Alex I.; Gladkova, Natalia D.

    2016-02-01

    We combined cross-polarization optical coherence tomography (CP OCT) and non-linear microscopy based on second harmonic generation (SHG) and two-photon-excited fluorescence (2PEF) to assess collagen and elastin fibers in the development of the atherosclerotic plaque (AP). The study shows potential of CP OCT for the assessment of collagen and elastin fibers condition in atherosclerotic arteries. Specifically, the additional information afforded by CP OCT, related to birefringence and cross-scattering properties of arterial tissues, may improve the robustness and accuracy of assessment about the microstructure and composition of the plaque for different stages of atherosclerosis.

  4. Chimney stent technique for treatment of severe abdominal aortic atherosclerotic stenosis.

    PubMed

    Ritter, Jens C; Ghosh, Jonathan; Butterfield, John S; McCollum, Charles N; Ashleigh, Raymond

    2011-03-01

    Application of the "chimney" stent technique is described in a case of complex multilevel atherosclerotic disease involving the juxtarenal aorta. A patient with significant comorbidities was unsuitable for major open reconstructive surgery. He was treated with a combined procedure consisting of chimney stent placement in the juxtarenal aorta, iliac "kissing" stent placement, and right-sided common femoral artery (CFA) replacement. This case shows that the chimney stent technique can be a feasible alternative to leaving a safety wire in the renal arteries and observation during primary angioplasty in complex atherosclerotic lesions of the abdominal aorta.

  5. Anatomical variation of arterial supply to the rabbit spleen

    PubMed Central

    IKEGAMI, Reona; TANIMOTO, Yoshimasa; KISHIMOTO, Miori; SHIBATA, Hideshi

    2015-01-01

    The rabbit, which is widely used as an experimental animal and is also popular as a companion animal, has a flat and elongated spleen with the longitudinal hilus running along its visceral surface. The spleen receives via the hilus an arterial supply that is essential for splenic nutrition and normal functioning. However, the distribution and variation of the arteries to the spleen have not been studied in detail. This study investigated anatomical variations of splenic arterial supply in 33 New Zealand White rabbits with a colored latex injection into arteries. We also examined whether the length of the spleen correlated with the number of the splenic branches of the splenic artery. The splenic artery always arose as the first independent branch of the celiac artery and ran along the splenic hilus to usually provide 6 (range, 3 to 10) splenic branches to the spleen. There was a moderate correlation (R=0.6) between the number of splenic branches and the longitudinal length of the spleen. The splenic branches often arose as a trunk or trunks in common with short gastric arteries. The number of common trunk(s) was usually 1 (range, 0 to 4). The data showed that the pattern and number of arterial branches to the spleen varied according to the individual animal, suggesting that such variations should be considered when performing experimental and veterinary surgical treatments in rabbits. PMID:26369291

  6. Transgenic Mouse Bioassay: Evidence That Rabbits Are Susceptible to a Variety of Prion Isolates

    PubMed Central

    Pintado, Belén; Eraña, Hasier; Ordóñez, Montserrat; Márquez, Mercedes; Chianini, Francesca; Fondevila, Dolors; Sánchez-Martín, Manuel A.; Andreoletti, Olivier; Dagleish, Mark P.; Pumarola, Martí; Castilla, Joaquín

    2015-01-01

    Interspecies transmission of prions is a well-established phenomenon, both experimentally and under field conditions. Upon passage through new hosts, prion strains have proven their capacity to change their properties and this is a source of strain diversity which needs to be considered when assessing the potential risks associated with consumption of prion contaminated protein sources. Rabbits were considered for decades to be a prion resistant species until proven otherwise recently. To determine the extent of rabbit susceptibility to prions and to assess the effects of passage of different prion strains through this species a transgenic mouse model overexpressing rabbit PrPC was developed (TgRab). Intracerebral challenges with prion strains originating from a variety of species including field isolates (ovine SSBP/1 scrapie, Nor98- scrapie; cattle BSE, BSE-L and cervid CWD), experimental murine strains (ME7 and RML) and experimentally obtained ruminant (sheepBSE) and rabbit (de novo NZW) strains were performed. On first passage TgRab were susceptible to the majority of prions (Cattle BSE, SheepBSE, BSE-L, de novo NZW, ME7 and RML) tested with the exception of SSBP/1 scrapie, CWD and Nor98 scrapie. Furthermore, TgRab were capable of propagating strain-specific features such as differences in incubation periods, histological brain lesions, abnormal prion (PrPd) deposition profiles and proteinase-K (PK) resistant western blotting band patterns. Our results confirm previous studies proving that rabbits are not resistant to prion infection and show for the first time that rabbits are susceptible to PrPd originating in a number of other species. This should be taken into account when choosing protein sources to feed rabbits. PMID:26247589

  7. Transgenic Mouse Bioassay: Evidence That Rabbits Are Susceptible to a Variety of Prion Isolates.

    PubMed

    Vidal, Enric; Fernández-Borges, Natalia; Pintado, Belén; Eraña, Hasier; Ordóñez, Montserrat; Márquez, Mercedes; Chianini, Francesca; Fondevila, Dolors; Sánchez-Martín, Manuel A; Andreoletti, Olivier; Dagleish, Mark P; Pumarola, Martí; Castilla, Joaquín

    2015-08-01

    Interspecies transmission of prions is a well-established phenomenon, both experimentally and under field conditions. Upon passage through new hosts, prion strains have proven their capacity to change their properties and this is a source of strain diversity which needs to be considered when assessing the potential risks associated with consumption of prion contaminated protein sources. Rabbits were considered for decades to be a prion resistant species until proven otherwise recently. To determine the extent of rabbit susceptibility to prions and to assess the effects of passage of different prion strains through this species a transgenic mouse model overexpressing rabbit PrPC was developed (TgRab). Intracerebral challenges with prion strains originating from a variety of species including field isolates (ovine SSBP/1 scrapie, Nor98- scrapie; cattle BSE, BSE-L and cervid CWD), experimental murine strains (ME7 and RML) and experimentally obtained ruminant (sheepBSE) and rabbit (de novo NZW) strains were performed. On first passage TgRab were susceptible to the majority of prions (Cattle BSE, SheepBSE, BSE-L, de novo NZW, ME7 and RML) tested with the exception of SSBP/1 scrapie, CWD and Nor98 scrapie. Furthermore, TgRab were capable of propagating strain-specific features such as differences in incubation periods, histological brain lesions, abnormal prion (PrPd) deposition profiles and proteinase-K (PK) resistant western blotting band patterns. Our results confirm previous studies proving that rabbits are not resistant to prion infection and show for the first time that rabbits are susceptible to PrPd originating in a number of other species. This should be taken into account when choosing protein sources to feed rabbits.

  8. Natural Pathogens of Laboratory Mice, Rats, and Rabbits and Their Effects on Research

    PubMed Central

    Baker, David G.

    1998-01-01

    Laboratory mice, rats, and rabbits may harbor a variety of viral, bacterial, parasitic, and fungal agents. Frequently, these organisms cause no overt signs of disease. However, many of the natural pathogens of these laboratory animals may alter host physiology, rendering the host unsuitable for many experimental uses. While the number and prevalence of these pathogens have declined considerably, many still turn up in laboratory animals and represent unwanted variables in research. Investigators using mice, rats, and rabbits in biomedical experimentation should be aware of the profound effects that many of these agents can have on research. PMID:9564563

  9. Distribution of selected elements in atherosclerotic plaques of apoE/LDLR-double knockout mice subjected to dietary and pharmacological treatments

    NASA Astrophysics Data System (ADS)

    Gajda, Mariusz; Kowalska, Joanna; Banaś, Agnieszka; Banaś, Krzysztof; Kwiatek, Wojciech M.; Kostogrys, Renata B.; Mateuszuk, łukasz; ChŁopicki, Stefan; Litwin, Jan A.; Appel, Karen

    2011-10-01

    Gene-targeted, apolipoprotein E and LDL receptor-double knockout (apoE/LDLR -/-) mice represent a new animal model that displays severe hyperlipidemia and atherosclerosis. The aim of the present study was to show changes in histomorphology and in distribution of selected elements in atherosclerotic plaques of apoE/LDLR -/- mice fed egg-rich proatherosclerotic diet (5% egg-yolk lyophilisate) supplemented or not with perindopril (inhibitor of angiotensin converting enzyme; 2 mg/kg b.w.). Synchrotron radiation micro-X-ray fluorescence spectrometry was combined with histological stainings to determine distribution and concentration of trace and essential elements in atherosclerotic lesions. More advanced atherosclerotic lesions expressed by total area occupied by lipids (oil red-O staining) and by macrophages (CD68 immunohistochemistry) were observed in animals fed egg-rich diet. The perindopril treatment attenuated these effects. No significant differences were observed in the number of intimal smooth muscle cells (smooth muscle actin immunohistochemistry). In animals fed egg-rich diet significantly higher concentrations of Ca and significantly lower contents of S, Cl, , Fe, Cu, Zn and Se in atheromas were seen in comparison to chow diet-fed animals. After pharmacological treatment, concentrations of S, Cl, Fe, Cu, Zn and Se showed the tendency to achieve levels like in animals fed normal diet. K level differed only in group treated with perindopril. Concentration of P did not significantly vary in all experimental groups. Perindopril showed its potency to reduce atherosclerosis, as estimated by the size of the atheroma and content of pro- and antiatherogenic elements.

  10. Sulforaphane attenuates the development of atherosclerosis and improves endothelial dysfunction in hypercholesterolemic rabbits

    PubMed Central

    Suddek, Ghada M

    2016-01-01

    The aim of the present work was to explore possible protective effects of sulforaphane (SFN) against atherosclerosis development and endothelial dysfunction in hypercholesterolemic rabbits. Rabbits were assigned to three groups of five: group I fed normal chow diet for four weeks, group II fed 1% high cholesterol diet (HCD) and group III fed HCD + SFN (0.25 mg/kg/day). Blood samples were collected for measurement of serum triglycerides (TGs), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), lactate dehydrogenase (LDH) and C-reactive protein (CRP). Aortic malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and total nitrite/nitrate (NOx) were measured. Vascular reactivity and intima/media (I/M) ratio were analyzed. Nuclear factor-kappa B (NF-κB) activation in aortic endothelial cells was identified immunohistochemically. HCD induced significant increases in serum TGs, TC, LDL-C, LDH, and CRP, and aortic MDA and SOD. Moreover, HCD caused significant reductions in serum HDL-C, aortic GSH and NOx. SFN administration significantly decreased HCD-induced elevations in serum TC, LDL-C, CRP, and LDH. while significantly increased HDL-C and GSH levels and normalized aortic SOD and NOx. Additionally, SFN significantly improved rabbit aortic endothelium-dependent relaxation to acetylcholine. Moreover, SFN significantly reduced the elevation in I/M ratio. This effect was confirmed by aortic histopathologic examination. The expression of NF-κB in aortic tissue showed a marked reduction upon treatment with SFN. In conclusion, this study reveals that SFN has the ability to ameliorate HCD-induced atherosclerotic lesions progression and vascular dysfunction, possibly via its lipid-lowering and antioxidant effects and suppression of NF-κB-mediated inflammation. PMID:26490346

  11. Characterization of a novel alphaherpesvirus associated with fatal infections of domestic rabbits

    SciTech Connect

    Jin, L. Loehr, C.V.; Vanarsdall, A.L.; Baker, R.J.; Moerdyk-Schauwecker, M.; Levine, C.; Gerlach, R.F.; Cohen, S.A.; Alvarado, D.E.; Rohrmann, G.F.

    2008-08-15

    A virus was found to be associated with a severe disease affecting rabbits on a farm near Anchorage, Alaska. Extracts from the skin of infected rabbits produced syncytia and cell lysis in cultured rabbit skin, rabbit kidney, and Vero cells. Examination of the infectious agent by electron microscopy revealed an icosahedral nucleocapsid surrounded by an envelope with a diameter of about 120 nm, suggesting that it was a herpesvirus. The viral genome was determined to be composed of double-stranded DNA of 120-130 kbp. PCR using degenerate primers to conserved herpesvirus genes was used to amplify sequences from purified viral DNA. Sequencing of these products allowed the design of specific primers so that complete sequence data for a number of genes could be determined. Analysis of these data indicated that the virus is most closely related to bovine herpesvirus 2. The next most closely related viruses are human herpesviruses 1 and 2, and a number of cercopithecine herpesviruses. Experimental exposure of domestic rabbits to the isolate resulted in severe clinical disease and necrosis in the spleen and lymph node. In addition, viral DNA was identified in a variety of tissues by PCR, consistent with a systemic infection. Taken together, these data suggest that this virus is highly pathogenic for domestic rabbits and belongs to the family Herpesviridae, subfamily Alphaherpesvirinae, genus Simplexvirus.

  12. Effects of replacing groundnut cake with blood vegetable waste meal in the diets of weaner rabbits.

    PubMed

    Adeniji, Adedayo Abiodun

    2012-01-01

    A total of seventy-two weaner rabbits of eight weeks of age were used to assess the effects of replacing groundnut cake (GNC) with blood vegetable waste meal (BVWM) in the diets of rabbits. The BVWM was fed to replace dietary GNC at 0, 15, 30, and 45%, with GNC being 15% in the control diet. The four experimental diets were fed ad libitum for a period of eight weeks. BVWM was analyzed to contain a crude protein value of 62.35%. There were comparable feed intake values by rabbits on all the diets although the rabbits in the higher replacement levels of BVWM tended to have consumed more of the feed. There were significant increases (P < 0.05) in body weight gain by rabbits as the BVWM level increased in the diet. Similarly, the feed to gain ratio improved and nitrogen digestibility increased (P < 0.05) with higher levels of BVWM in the diet. This study shows that rabbits can tolerate the 45% BVWM replacement of groundnut cake effectively.

  13. 12- and 15-lipoxygenases in human carotid atherosclerotic lesions: Associations with cerebrovascular symptoms

    Technology Transfer Automated Retrieval System (TEKTR