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.

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

Apoptosis does not mediate macrophage depletion in rabbit atherosclerotic plaques after dietary lipid lowering.

PubMed

Martinet, Wim; Croons, Valerie; Herman, Arnold G; De Meyer, Guido R Y

2009-08-01

Unstable atherosclerotic plaques are characterized by a thin fibrous cap that contains few smooth muscle cells (SMCs) and numerous foam cells of macrophage origin. Previously we and others demonstrated that macrophages disappear from atherosclerotic plaques after dietary lipid lowering. However, it remains unclear whether loss of macrophages after lipid lowering occurs via increased apoptosis, decreased macrophage replication and/or recruitment, or via a combination of both. Rabbits were fed a diet supplemented with cholesterol (0.3%) for 24 weeks followed by a normal diet for 4, 12, or 24 weeks. After 24 weeks of cholesterol supplement, plaques showed apoptosis in both macrophages and SMCs, as determined by terminal deoxynucleotidyl transferase dUTP nick-end labeling. Cell replication (Ki-67 immunolabeling) was predominantly present in macrophages. After 24 weeks of cholesterol withdrawal, the thickness and areas of the plaques were unchanged. Nevertheless, plaques showed a considerable loss of macrophages. This event was associated with a reduced immunoreactivity for vascular cell adhesion molecule-1 (VCAM-1) in the endothelial cells starting 4 weeks after cholesterol withdrawal. Apoptosis did not increase after lipid lowering but showed a steady decline. Apart from decreased VCAM-1 expression, a strong decrease in Ki-67 immunolabeling was observed after 12 weeks of cholesterol withdrawal. Our findings suggest that loss of macrophages in atherosclerotic plaques after dietary lipid lowering is not related to induction of macrophage apoptosis but mainly a consequence of impaired monocyte recruitment followed by decreased macrophage replication. This information is essential for understanding the effects of aggressive lipid lowering on plaque stability.

The values of wall shear stress, turbulence kinetic energy and blood pressure gradient are associated with atherosclerotic plaque erosion in rabbits.

PubMed

Sameshima, Naoki; Yamashita, Atsushi; Sato, Shinya; Matsuda, Shuntaro; Matsuura, Yunosuke; Asada, Yujiro

2014-01-01

To clarify the contribution of hemodynamic factors to the onset of plaque erosion in smooth muscle cell (SMC)-rich atherosclerotic plaque. We developed a rabbit model of SMC-rich atherosclerotic plaque with various degree of stenosis induced by incomplete ligation and generated three-dimensional models of five rabbit femoral arteries based on 130-162 serial histological cross-sections at 100-μm intervals per artery. We performed a computational blood flow simulation using the Reynolds-averaged Navier-Stokes model and calculated the wall shear stress (WSS), turbulence kinetic energy (TKE), blood pressure (BP) and blood pressure gradients (BPG) in eight sections (the inlet, the stenotic portion and areas 1, 2 and 5mm from the stenotic portion) in each rabbit. We also investigated whether the magnitude of WSS or TKE was related to the presence or absence of erosive injury by evaluating six points (the locally highest, median and lowest of WSS or TKE) in each section. The magnitudes of WSS, TKE and BPG, but not BP, correlated significantly with the extent of histologically-defined plaque erosion (WSS, r=0.55, p＜0.001; TKE, r=0.53, p＜0.001; BPG, r=0.61, p＜0.0001, n=40). The values for WSS and TKE were significantly larger at sites with, compared to without, erosive injury (n=107 and n=119 points, respectively; both p＜0.0001). These results suggest that increased values of WSS, TKE and BPG considerably contribute to the onset of plaque erosion.

Spatio-temporal texture (SpTeT) for distinguishing vulnerable from stable atherosclerotic plaque on dynamic contrast enhancement (DCE) MRI in a rabbit model

PubMed Central

Wan, Tao; Madabhushi, Anant; Phinikaridou, Alkystis; Hamilton, James A.; Hua, Ning; Pham, Tuan; Danagoulian, Jovanna; Kleiman, Ross; Buckler, Andrew J.

2014-01-01

Purpose: To develop a new spatio-temporal texture (SpTeT) based method for distinguishing vulnerable versus stable atherosclerotic plaques on DCE-MRI using a rabbit model of atherothrombosis. Methods: Aortic atherosclerosis was induced in 20 New Zealand White rabbits by cholesterol diet and endothelial denudation. MRI was performed before (pretrigger) and after (posttrigger) inducing plaque disruption with Russell's-viper-venom and histamine. Of the 30 vascular targets (segments) under histology analysis, 16 contained thrombus (vulnerable) and 14 did not (stable). A total of 352 voxel-wise computerized SpTeT features, including 192 Gabor, 36 Kirsch, 12 Sobel, 52 Haralick, and 60 first-order textural features, were extracted on DCE-MRI to capture subtle texture changes in the plaques over the course of contrast uptake. Different combinations of SpTeT feature sets, in which the features were ranked by a minimum-redundancy-maximum-relevance feature selection technique, were evaluated via a random forest classifier. A 500 iterative 2-fold cross validation was performed for discriminating the vulnerable atherosclerotic plaque and stable atherosclerotic plaque on per voxel basis. Four quantitative metrics were utilized to measure the classification results in separating between vulnerable and stable plaques. Results: The quantitative results show that the combination of five classes of SpTeT features can distinguish between vulnerable (disrupted plaques with an overlying thrombus) and stable plaques with the best AUC values of 0.9631 ± 0.0088, accuracy of 89.98% ± 0.57%, sensitivity of 83.71% ± 1.71%, and specificity of 94.55% ± 0.48%. Conclusions: Vulnerable and stable plaque can be distinguished by SpTeT based features. The SpTeT features, following validation on larger datasets, could be established as effective and reliable imaging biomarkers for noninvasively assessing atherosclerotic risk. PMID:24694153

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

PubMed Central

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

2015-01-01

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

Detection of Vulnerable Atherosclerotic Plaques in Experimental Atherosclerosis with the USPIO-Enhanced MRI.

PubMed

Qi, Chun-Mei; Du, Lili; Wu, Wei-Heng; Li, Dong-Ye; Hao, Ji; Gong, Lei; Deng, Liangrong; Zhang, Tao; Zhang, Chao; Zhang, Yu

2015-11-01

This study's goal was to assess the diagnostic value of the USPIO-(ultra-small superparamagnetic iron oxide) enhanced magnetic resonance imaging (MRI) in detection of vulnerable atherosclerotic plaques in abdominal aorta in experimental atherosclerosis. Thirty New Zealand rabbits were randomly divided into two groups, Group A and Group B. Each group comprised 15 animals which were fed with high cholesterol diet for 8 weeks and then subjected to balloon-induced endothelial injury of the abdominal aorta. After another 8 weeks, animals in Group B received adenovirus carrying p53 gene that was injected through a catheter into the aortic segments rich in plaques. Two weeks later, all rabbits were challenged with the injection of Chinese Russell's viper venom and histamine. Pre-contrast images and USPIO-enhanced MRI images were obtained after pharmacological triggering with injection of USPIO for 5 days. Blood specimens were taken for biochemical and serological tests at 0 and 18 weeks. Abdominal aorta was histologically studied. The levels of serum ICAM-1 and VCAM-1 were quantified by ELISA. Vulnerable plaques appeared as a local hypo-intense signal on the USPIO-enhanced MRI, especially on T2*-weighted sequences. The signal strength of plaques reached the peak at 96 h. Lipid levels were significantly (p < 0.05) higher in both Group A and B compared with the levels before the high cholesterol diet. The ICAM-1 and VCAM-1 levels were significantly (p < 0.05) higher in Group B compared with Group A. The USPIO-enhanced MRI efficiently identifies vulnerable plaques due to accumulation of USPIO within macrophages in abdominal aorta plaques.

EXPERIMENTAL ATHEROSCLEROSIS AND BLOOD PRESSURE IN THE RABBIT

PubMed Central

Dominguez, R.

1927-01-01

1. Van Leersum's range for the normal blood pressure in the rabbit, as recorded by his method, is confirmed. 2. Van Leersum's conclusion concerning the influence of a liver diet on the blood pressure of the rabbit is not substantiated by his data, since the fluctuations of blood pressure he obtained do not surpass his own recorded figures for normal animals. 3. Fluctuations of systolic blood pressure beyond the "normal" range are not necessary for the production of experimental atherosclerosis of the aorta in rabbits. Inversely, egg yolk feeding experiments in rabbits in which atherosclerosis of varying degree, even extreme, is obtained, are not accompanied by an elevation of blood pressure outside the "normal" range. 4. The fluctuations of blood pressure observed during experimental atherosclerosis do not simulate the condition of essential hypertension in man. PMID:19869349

Vasospasm of atherosclerotic coronary arteries precipitates acute ischemic myocardial damage in myocardial infarction-prone strain of the Watanabe heritable hyperlipidemic rabbits.

PubMed

Shiomi, Masashi; Ishida, Tatsuro; Kobayashi, Tsutomu; Nitta, Norihisa; Sonoda, Akinaga; Yamada, Satoshi; Koike, Tomonari; Kuniyoshi, Nobue; Murata, Kiyoshi; Hirata, Ken-ichi; Ito, Takashi; Libby, Peter

2013-11-01

This study tested the hypothesis that vasospasm can trigger coronary plaque injury and acute ischemic myocardial damage. Myocardial infarction-prone strain of the Watanabe heritable hyperlipidemic rabbits received an intravenous bolus of ergonovine maleate (0.45 µmol/kg) during intravenous infusion of norepinephrine (12 nmol/kg per minute) to provoke coronary spasm in vivo. After this treatment, coronary angiography demonstrated vasospasm, and the ECG showed ischemic abnormalities (ST depression/elevation and T-wave inversion) in 77% of animals (23/30). These changes normalized after nitroglycerin injection. In rabbits that demonstrated these ECG findings for >20 minutes, echocardiograms showed left ventricular wall motion abnormality. Serum levels of heart-type fatty acid-binding protein, cardiac troponin-I, and myoglobin increased markedly 4 hours after spasm provocation. In coronary lesions of myocardial infarction-prone strain of the Watanabe heritable hyperlipidemic rabbits with provoked coronary spasm, we observed intimal injury in 60.9% in the form of endothelial cell protrusions (39.1%), denudation (30.4%), and macrophage extravasation (56.5%). Plaque disruption with luminal thrombus, however, was only seen in 2 of 23 animals (8.7%), and mural microthrombus was rarely observed (4.3%). These observations show that provocation of vasospasm in myocardial infarction-prone strain of the Watanabe heritable hyperlipidemic rabbits associates with subsequent ischemic myocardial damage. Although treatment with spasmogens altered aspects of plaque morphology, for example, endothelial protrusion and macrophage emigration, thrombosis was rare in these animals with chronic atherosclerotic disease.

Measurement of drug and macromolecule diffusion across atherosclerotic rabbit aorta ex vivo by attenuated total reflection-Fourier transform infrared imaging

NASA Astrophysics Data System (ADS)

Palombo, Francesca; Danoux, Charlène B.; Weinberg, Peter D.; Kazarian, Sergei G.

2009-07-01

Diffusion of two model drugs-benzyl nicotinate and ibuprofen-and the plasma macromolecule albumin across atherosclerotic rabbit aorta was studied ex vivo by attenuated total reflection-Fourier transform infrared (ATR-FTIR) imaging. Solutions of these molecules were applied to the endothelial surface of histological sections of the aortic wall that were sandwiched between two impermeable surfaces. An array of spectra, each corresponding to a specific location in the section, was obtained at various times during solute diffusion into the wall and revealed the distribution of the solutes within the tissue. Benzyl nicotinate in Ringer's solution showed higher affinity for atherosclerotic plaque than for apparently healthy tissue. Transmural concentration profiles for albumin demonstrated its permeation across the section and were consistent with a relatively low distribution volume for the macromolecule in the middle of the wall. The ability of albumin to act as a drug carrier for ibuprofen, otherwise undetected within the tissue, was demonstrated by multivariate subtraction image analysis. In conclusion, ATR-FTIR imaging can be used to study transport processes in tissue samples with high spatial and temporal resolution and without the need to label the solutes under study.

Advances in non-invasive drug delivery for atherosclerotic heart disease.

PubMed

Maranhão, Raul C; Tavares, Elaine R

2015-07-01

Apart from statins, anti-platelet agents and invasive procedures, the anti-atherosclerotic medical weaponry for coronary heart disease (CHD) is scarce and only partially protects CHD patients from major adverse cardiac events. Several novel non-invasive strategies are being developed to widen the therapeutic options. Among them, drug delivery tools were tested in vivo encompassing liposomes, micelles, polymeric, metallic and lipid nanoparticles used as carriers of statins, corticosteroids, a bisphosphonate, a glitazone, anti-cancer agents, a mycotoxin, a calcium channel blocker and a compound of traditional Chinese medicine. All preparations improved parameters related to atherosclerotic lesions induced in rabbits, rats and mice and reduced neointima formation in experiments aiming to prevent post-stenting restenosis. In subjects submitted to percutaneous coronary intervention, nanoparticle formulations of paclitaxel and alendronate showed safety but are still not conclusive regarding in-stent late loss. The experience of our group in atherosclerotic rabbits treated with non-protein lipid nanoparticles associated with anti-cancer drugs such as paclitaxel, etoposide and methotrexate is summarized, and preliminary safety data in CHD patients are anticipated. Taken together, these studies show that non-invasive drug-delivery systems may become promising tools to rescue CHD patients from the risks of severe and life-threatening lesions that should be more energetically treated.

Intravascular photoacoustic imaging of exogenously labeled atherosclerotic plaque through luminal blood

NASA Astrophysics Data System (ADS)

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

2012-10-01

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

Hypolipidemic effect of arborium plus in experimentally induced hypercholestermic rabbits.

PubMed

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

2010-06-01

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

Comparison of the endothelial coverage in everolimus and zotarolimus-eluting stents in normal, atherosclerotic, and bifurcation rabbit iliac arteries.

PubMed

Torii, Sho; Nakazawa, Gaku; Ijichi, Takeshi; Yoshikawa, Ayako; Ohno, Yohei; Ikari, Yuji

2018-01-01

The aim of this study is to evaluate differences in stent endothelial coverage among the second generation of drug-eluting stents. Incomplete stent coverage is one of the major causes of late stent thrombosis. Rabbits fed a normal diet received an everolimus (Xience Prime; EES) and a zotarolimus-eluting stent (Resolute Integrity; R-ZES) in each iliac artery, followed by sacrifice at 14 and 28 days after stent implantation. In addition, a group of atherosclerotic rabbits similarly received EES and R-ZES, and were sacrificed at 28 days. The extent of stent endothelial coverage was assessed by scanning electron microscopy. To evaluate endothelial coverage after bifurcation stenting, rabbits received EES and R-ZES placed with culotte stenting at the iliac bifurcation, followed by sacrifice at 14 and 28 days. In rabbits fed a normal diet, the percent uncovered strut area 14 days after stent implantation was significantly higher in R-ZES than in EES (10.1% (IQR 9.8-15.5) vs. 3.0% (IQR 1.5-9.7), p = 0.03), whereas it was not significantly different at 28-days (3.9% (IQR 0.8-10.3) vs. 1.0% (IQR 0.0-2.8), p = 0.2). In rabbits with induced atheroma, R-ZES also showed less endothelial coverage 28 days after stent implantation (5.3% (IQR 2.2-9.9) vs. 1.1% (IQR 0-6.2), p = 0.03). In the culotte stenting model, the percent uncovered strut area of the proximal overlapped segment was significantly higher in R-ZES at 14 days (15.8% (IQR 14.3-17.7) vs. 8.8% (IQR 8.3-9.8), p = 0.03) and 28 days (9.9% (IQR 4.1-13.9) vs. 2.5% (IQR 1.6-6.7), p = 0.04) after stent implantation. The carina area also showed a better coverage in EES compared with R-ZES. EES showed a better stent endothelial coverage compared with R-ZES after stent implantation in the early phase in normals, in arteries with lipid rich plaque, and in bifurcation stented sites.

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.

A single-photon fluorescence and multi-photon spectroscopic study of atherosclerotic lesions

NASA Astrophysics Data System (ADS)

Smith, Michael S. D.; Ko, Alex C. T.; Ridsdale, Andrew; Schattka, Bernie; Pegoraro, Adrian; Hewko, Mark D.; Shiomi, Masashi; Stolow, Albert; Sowa, Michael G.

2009-06-01

In this study we compare the single-photon autofluorescence and multi-photon emission spectra obtained from the luminal surface of healthy segments of artery with segments where there are early atherosclerotic lesions. Arterial tissue was harvested from atherosclerosis-prone WHHL-MI rabbits (Watanabe heritable hyperlipidemic rabbit-myocardial infarction), an animal model which mimics spontaneous myocardial infarction in humans. Single photon fluorescence emission spectra of samples were acquired using a simple spectrofluorometer set-up with 400 nm excitation. Samples were also investigated using a home built multi-photon microscope based on a Ti:sapphire femto-second oscillator. The excitation wavelength was set at 800 nm with a ~100 femto-second pulse width. Epi-multi-photon spectroscopic signals were collected through a fibre-optics coupled spectrometer. While the single-photon fluorescence spectra of atherosclerotic lesions show minimal spectroscopic difference from those of healthy arterial tissue, the multi-photon spectra collected from atherosclerotic lesions show marked changes in the relative intensity of two-photon excited fluorescence (TPEF) and second-harmonic generation (SHG) signals when compared with those from healthy arterial tissue. The observed sharp increase of the relative SHG signal intensity in a plaque is in agreement with the known pathology of early lesions which have increased collagen content.

[Expression and antagonist role of endothelin and nitric oxide synthase in atherosclerotic plaque].

PubMed

Song, L; Wang, D; Wang, T

1997-02-01

To study the pathogenetic mechanism of atherosclerotic plaque, the action of mediation and antagonism of endothelin (ET) and nitric oxide synthase (NOS) was investigated. In situ hybridization, RT-PCR on endothelin and NOS, cytochemistry on NOS were measured using the rabbit atherosclerosis model and cultured vascular smooth muscle cells (VSMC) from normal rabbit. Transcription of endothelin mRNA increased and transcription of NOS mRNA decreased in astherosclerotic plaque: compared with normal aorta, expression of ET gene in plaque was increased by 1.2 times and the expression of NOS gene was decreased by 22.2%; cytochemistry combined with image pattern analysis showed that ET could inhibit NOS protien synthesis in VSMC; type A receptor antagonist of ET could inhibit the role of ET which causes a decrease of NOS protein in VSMC. The imbalance between NOS and ET, namely abnormal increase of ET and/or obvious decrease of NOS, is related to atherosclerotic plaque formation.

Recombinant apolipoprotein A-I Milano rapidly reverses aortic valve stenosis and decreases leaflet inflammation in an experimental rabbit model.

PubMed

Speidl, Walter S; Cimmino, Giovanni; Ibanez, Borja; Elmariah, Sammy; Hutter, Randolph; Garcia, Mario J; Fuster, Valentin; Goldman, Martin E; Badimon, Juan J

2010-08-01

Aortic stenosis (AS) is associated with significant morbidity and mortality. Recombinant apolipoprotein A-I Milano (rApoA-I(M)) induces atherosclerotic plaque regression. The aims of this study were to determine the effects of rApoA-I(M) on experimental aortic valve degeneration and its mechanisms of action. New Zealand White rabbits (n = 20) were fed an atherogenic diet for 9 months and then randomized to either placebo or rApoA-I(M). Echocardiography was used to assess the effect of the treatments on AS. Porcine aortic valve myofibroblasts (PAVMF) treated with oxidized low-density lipoprotein served to define the effects of rApoA-I(M) on the expression of monocyte chemoattractant protein-1 (MCP-1), nuclear factor (NF)-kappaB, and alkaline phosphatase (AP). Recombinant apolipoprotein A-I Milano increased aortic valve area (AVA) by 32% (0.25 +/- 0.05 to 0.34 +/- 0.07 cm(2), P < 0.01); whereas AVA remained unchanged in the placebo group (0.24 +/- 0.05 to 0.26 +/- 0.04 cm(2), P = 0.58). Histopathological examination of aortic valves in the rApoA-I(M) animals showed significantly less leaflet thickening, inflammation, and calcification vs. the placebo group. In vitro, rApoA-I(M) significantly inhibited MCP-1, AP, and NF-kappaB and decreased intracellular cholesterol content in PAVMF. Recombinant apolipoprotein A-I Milano treatment reverses AS in this experimental rabbit model. The beneficial effects seem to be mediated by enhanced cholesterol removal and by reduced inflammation and calcification.

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

PubMed

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

2016-10-15

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

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

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

PubMed

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

2005-08-01

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.

Differentiation of artery wall lesions using porphyrins and fiberoptic sensor in rabbits

NASA Astrophysics Data System (ADS)

Vari, Sandor G.; van der Veen, Maurits J.; Papazoglou, Theodore G.; Fishbein, Michael C.; Stavridi, Marigo; Papaioannou, Thanassis; Grundfest, Warren S.

1994-02-01

We investigated the ability of fluorescence spectroscopy, and photosensitizers to differentiate normal, hyperplastic and atherosclerotic arterial wall lesions in vivo. Hyperplastic lesions were induced in the abdominal aorta (AB) of 24 rabbits by balloon injury (BI). Atherosclerotic arterial wall lesions were induced by BI and diet. Fluorescence signals from thoracic n equals 16 and AB n equals 15 sites were analyzed by computer. A ratio was used as an index of drug presence. Use of PPS or BPD and LIFS may be a feasible, in vivo method for the differentiation between normal, hyperplastic and atherosclerotic arterial wall lesions.

Particulate matter air pollution exposure promotes recruitment of monocytes into atherosclerotic plaques.

PubMed

Yatera, Kazuhiro; Hsieh, Joanne; Hogg, James C; Tranfield, Erin; Suzuki, Hisashi; Shih, Chih-Horng; Behzad, Ali R; Vincent, Renaud; van Eeden, Stephan F

2008-02-01

Epidemiologic studies have shown an association between exposure to ambient particulate air pollution <10 microm in diameter (PM(10)) and increased cardiovascular morbidity and mortality. We previously showed that PM(10) exposure causes progression of atherosclerosis in coronary arteries. We postulate that the recruitment of monocytes from the circulation into atherosclerotic lesions is a key step in this PM(10)-induced acceleration of atherosclerosis. The study objective was to quantify the recruitment of circulating monocytes into vessel walls and the progression of atherosclerotic plaques induced by exposure to PM(10). Female Watanabe heritable hyperlipidemic rabbits, which naturally develop systemic atherosclerosis, were exposed to PM(10) (EHC-93) or vehicle by intratracheal instillation twice a week for 4 wk. Monocytes, labeled with 5-bromo-2'-deoxyuridine (BrdU) in donors, were transfused to recipient rabbits as whole blood, and the recruitment of BrdU-labeled cells into vessel walls and plaques in recipients was measured by quantitative histological methodology. Exposure to PM(10) caused progression of atherosclerotic lesions in thoracic and abdominal aorta. It also decreased circulating monocyte counts, decreased circulating monocytes expressing high levels of CD31 (platelet endothelial cell adhesion molecule-1) and CD49d (very late antigen-4 alpha-chain), and increased expression of CD54 (ICAM-1) and CD106 (VCAM-1) in plaques. Exposure to PM(10) increased the number of BrdU-labeled monocytes adherent to endothelium over plaques and increased the migration of BrdU-labeled monocytes into plaques and smooth muscle underneath plaques. We conclude that exposure to ambient air pollution particles promotes the recruitment of circulating monocytes into atherosclerotic plaques and speculate that this is a critically important step in the PM(10)-induced progression of atherosclerosis.

Uniaxial Tensile Properties of Atherosclerotic Carotid Artery After Mobilization of Pushing on Qiao-Gong: A Safety Study Using an Animal Model of Carotid Atherosclerosis.

PubMed

Qi, Ji; Zhang, Shaoqun; Zhang, Lei; Ping, Ruiyue; Ping, Kaike; Ye, Da; Shen, Honggui; Chen, Yili; Li, Yikai

2018-02-01

This study aimed to preliminarily explore the effects of the soft tissue mobilization of pushing on Qiao-Gong (MPQ) on biomechanical properties of the carotid artery using an animal model of carotid atherosclerosis (CAS). Fifty rabbits were randomly divided into 4 groups: animals with CAS treated with MPQ (CAS-MPQ [n = 15]); animals with CAS treated without MPQ (CAS [n = 15]); normal animals treated with MPQ (normal-MPQ [n = 10]); and a blank control group (n = 10). The MPQ procedure consisted of soft tissue mobilization of the Qiao-Gong acupoint on the front edge of the sternocleidomastoid muscle applied from top to bottom, by flat pushing with the thumb repeatedly for 20 times. Disease in the CAS models was induced by carotid artery balloon injury combined with a high-fat diet for 12 weeks. At the end of modeling, carotid color Doppler ultrasonography examination was performed to confirm which animal models were successfully induced with CAS, excluding model rabbits without typical CAS at the same time. Then, MPQ was applied on rabbits in the CAS-MPQ and the normal-MPQ groups for 3 weeks. By contrast, rabbits in the other 2 groups were fed normally without MPQ. Uniaxial failure tests were later performed on carotid arteries in all 4 groups, and at the end of the study, a 2-way factorial analysis of variance of the results was conducted. (1) At the end of modeling, 10 rabbits in the CAS-MPQ group and 9 in the CAS group were included with typical carotid atherosclerotic characteristics. (2) Young's elastic modulus of the rabbit carotid artery increased more significantly in the CAS-MPQ group than the CAS group. (3) Compared with normal rabbit carotid arteries, atherosclerotic carotid arteries had lower levels of ultimate stress and ultimate strain but higher levels of ultimate load. The uniaxial tensile mechanical properties of the rabbit atherosclerotic carotid artery were impaired after MPQ. Copyright © 2018. Published by Elsevier Inc.

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

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

PubMed

Franklyn, Melanie; Field, Bruce

2013-01-01

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

Ezetimibe reduces plaque inflammation in a rabbit model of atherosclerosis and inhibits monocyte migration in addition to its lipid-lowering effect

PubMed Central

Gómez-Garre, D; Muñoz-Pacheco, P; González-Rubio, ML; Aragoncillo, P; Granados, R; Fernández-Cruz, A

2009-01-01

Background and purpose: Ezetimibe, a selective inhibitor of intestinal cholesterol absorption, might also suppress inflammatory components of atherogenesis. We have studied the effects of ezetimibe on two characteristics of atherosclerotic plaques (infiltrate and fibrosis) and on expression of inflammatory genes in a rabbit model of accelerated atherosclerosis. Experimental approach: Femoral atherosclerosis was induced by a combination of endothelial desiccation and atherogenic diet. Animals were randomized to ezetimibe (0.6 mg·kg−1·day−1), simvastatin (5 mg·kg−1·day−1), ezetimibe plus simvastatin or no treatment, still on atherogenic diet. A control group of rabbits received normolipidemic diet. Key results: Rabbits fed the normolipidemic diet showed normal plasma lipid levels. Either the normolipidemic diet or drug treatment reduced the intima/media ratio (normolipidemic diet: 22%, ezetimibe: 13%, simvastatin: 27%, ezetimibe + simvastatin: 28%), compared with rabbits with atherosclerosis. Ezetimibe also decreased macrophage content and monocyte chemoattractant protein-1 expression in atherosclerotic lesions. Furthermore, ezetimibe reduced the increased activity of nuclear factor κB in peripheral blood leucocytes and plasma C-reactive protein levels in rabbits with atherosclerosis. In THP-1 cells, ezetimibe decreased monocyte chemoattractant protein-1-induced monocyte migration. Importantly, the combination of ezetimibe with simvastatin was associated with a more significant reduction in plaque monocyte/macrophage content and some proinflammatory markers than observed with each drug alone. Conclusions and implications: Ezetimibe had beneficial effects both on atherosclerosis progression and plaque stabilization and showed additional anti-atherogenic benefits when combined with simvastatin. Its effect on monocyte migration provides a potentially beneficial action, in addition to its effects on lipids. PMID:19222481

Mesenchymal Stem Cells Stabilize Atherosclerotic Vulnerable Plaque by Anti-Inflammatory Properties.

PubMed

Wang, Shuang-shuang; Hu, Si-wang; Zhang, Qing-hua; Xia, Ai-xiang; Jiang, Zhi-xin; Chen, Xiao-min

2015-01-01

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. 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. 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 the VP group. .Immunohistochemistry analysis revealed

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo Yanhong; Chen Kuanghueih; Gao Wei

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% andmore » 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.« less

H19, a marker of developmental transition, is reexpressed in human atherosclerotic plaques and is regulated by the insulin family of growth factors in cultured rabbit smooth muscle cells.

PubMed

Han, D K; Khaing, Z Z; Pollock, R A; Haudenschild, C C; Liau, G

1996-03-01

H19 is a developmentally regulated gene with putative tumor suppressor activity, and loss of H19 expression may be involved in Wilms' tumorigenesis. In this report, we have performed in situ hybridization analysis of H19 expression during normal rabbit development and in human atherosclerotic plaques. We have also used cultured smooth muscle cells to identify H19 regulatory factors. Our data indicate that H19 expression in the developing skeletal and smooth muscles correlated with specific differentiation events in these tissues. Expression of H19 in the skeletal muscle correlated with nonproliferative, actin-positive muscle cells. In the prenatal blood vessel, H19 expression was both temporally and spatially regulated with initial loss of expression in the inner smooth muscle layers adjacent to the lumen. We also identified H19-positive cells within the adult atherosclerotic lesion and we suggest that these cells may recapitulate earlier developmental events. These results, along with the identification of the insulin family of growth factors as potent regulatory molecules for H19 expression, provide additional clues toward understanding the physiological regulation and function of H19.

H19, a marker of developmental transition, is reexpressed in human atherosclerotic plaques and is regulated by the insulin family of growth factors in cultured rabbit smooth muscle cells.

PubMed Central

Han, D K; Khaing, Z Z; Pollock, R A; Haudenschild, C C; Liau, G

1996-01-01

H19 is a developmentally regulated gene with putative tumor suppressor activity, and loss of H19 expression may be involved in Wilms' tumorigenesis. In this report, we have performed in situ hybridization analysis of H19 expression during normal rabbit development and in human atherosclerotic plaques. We have also used cultured smooth muscle cells to identify H19 regulatory factors. Our data indicate that H19 expression in the developing skeletal and smooth muscles correlated with specific differentiation events in these tissues. Expression of H19 in the skeletal muscle correlated with nonproliferative, actin-positive muscle cells. In the prenatal blood vessel, H19 expression was both temporally and spatially regulated with initial loss of expression in the inner smooth muscle layers adjacent to the lumen. We also identified H19-positive cells within the adult atherosclerotic lesion and we suggest that these cells may recapitulate earlier developmental events. These results, along with the identification of the insulin family of growth factors as potent regulatory molecules for H19 expression, provide additional clues toward understanding the physiological regulation and function of H19. PMID:8636440

Is the Use of Fullerene in Photodynamic Therapy Effective for Atherosclerosis?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nitta, Norihisa, E-mail: r34nitta@belle.shiga-med.ac.jp; Seko, Ayumi; Sonoda, Akinaga

2008-03-15

The purpose of this study was to evaluate Fullerene as a therapeutic photosensitizer in the treatment of atherosclerosis. An atherosclerotic experimental rabbit model was prepared by causing intimal injury to bilateral external iliac arteries using balloon expansion. In four atherosclerotic rabbits and one normal rabbit, polyethylene glycol-modified Fullerene (Fullerene-PEG) was infused into the left external iliac artery and illuminated by light emitting diode (LED), while the right external iliac artery was only illuminated by LED. Two weeks later, the histological findings for each iliac artery were evaluated quantitatively and comparisons were made among atherosclerotic Fullerene+LED artery (n = 4), atheroscleroticmore » light artery (n = 4), normal Fullerene+LED artery (n = 1), and normal light artery (n = 1). An additional two atherosclerotic rabbits were studied by fluorescence microscopy, after Fullerene-PEG-Cy5 complex infusion into the left external iliac artery, for evaluation of Fullerene-PEG incorporated within the atherosclerotic lesions. The degree of atherosclerosis in the atherosclerotic Fullerene+LED artery was significantly (p < 0.05) more severe than that in the atherosclerotic LED artery. No pathological change was observed in normal Fullerene+LED and LED arteries. In addition, strong accumulation of Fullerene-PEG-Cy5 complex within the plaque of the left iliac artery of the two rabbits was demonstrated, in contrast to no accumulation in the right iliac artery. We conclude that infusion of a high concentration of Fullerene-PEG followed by photo-illumination resulted not in a suppression of atherosclerosis but in a progression of atherosclerosis in experimental rabbit models. However, this intervention showed no adverse effects on the normal iliac artery.« less

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.

Effect of rosuvastatin on atherosclerotic plaque stability: An intravascular ultrasound elastography study.

PubMed

Li, Zhaohuan; Wang, Lin; Hu, Xiaobo; Zhang, Pengfei; Chen, Yifei; Liu, Xinxin; Xu, Mingjun; Zhang, Yun; Zhang, Mei

2016-05-01

The present study aimed to investigate the effect of potent rosuvastatin therapy on plaque mechanical stabilization as seen on IVUSE. 14 purebred New Zealand rabbits were fed a high-cholesterol diet; the abdominal aorta endothelium was balloon-injured after 2 weeks; at week 13, 7 rabbits received rosuvastatin (1.5 mg/kg/day), and the other 7 received an equal volume of saline. IVUS images of abdominal aortas were acquired, and 2 consecutive frames near the end-diastole images in situ were used to construct an IVUS elastogram. Control rabbits showed a significant increase in shear strain (SS) and area strain (AS) in total plaques. The rosuvastatin group showed no change in SS and AS, but serum TG and LDL-C levels were reduced, with less lipid deposition, macrophage infiltration, production of proinflammatory cytokines and apoptosis in plaques. The changes in SS and AS from baseline between groups significantly differed (SS: 1.15 (1.96) % vs. -0.99 ± 2.83%, p = 0.013; AS: 1.25 (2.29) % vs. -1.67 ± 5.05%, p = 0.022). At follow-up, for controls, strain values were increased in the shoulder of eccentric plaques (SS: 2.66 ± 1.31% vs. 4.86 ± 1.93%, p = 0.016; AS: 4.45 ± 2.33% vs. 7.91 ± 2.74%, p = 0.009) but not the plaque body. Changes in SS and AS in the plaque shoulder differed between the control and rosuvastatin groups (SS: 2.20 ± 2.17% vs. -0.87 ± 3.31%, p = 0.028; AS: 2.10 (4.61) % vs. -2.75 ± 5.97%, p = 0.009). Rosuvastatin therapy in rabbits with atherosclerotic plaques led to less vulnerable plaque features. IVUSE is a very sensitive technique for detecting pharmacologically-induced mechanical changes in rabbit atherosclerotic plaques. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Kefiran reduces atherosclerosis in rabbits fed a high cholesterol diet.

PubMed

Uchida, Masashi; Ishii, Itsuko; Inoue, Chika; Akisato, Yoshie; Watanabe, Kenta; Hosoyama, Saori; Toida, Toshihiko; Ariyoshi, Noritaka; Kitada, Mitsukazu

2010-09-30

Kefiran is an exopolysaccharide produced by Lactobacillus kefiranofaciens, and has been proposed to have many health-promoting properties. We investigated the antiatherogenic effect of kefiran on rabbits fed a high-cholesterol diet. Male New Zealand White rabbits were fed a 0.5% cholesterol diet without (control group, n = 7) or with kefiran (kefiran group, n = 8) for eight weeks. The aorta was analyzed by histochemistry and atherosclerotic lesions were quantified. Lipids and sugars in serum were measured. Foam cell formation of RAW264.7 by βVLDL derived from both groups of rabbits was also investigated. Cholesterol, triglyceride and phospholipids levels of serum and lipoprotein fractions were not significantly different between these groups. Atherosclerotic lesions of the aorta in the kefiran group were statistically lower than those of the control group, with marked differences in the abdominal aorta. T-lymphocytes were not detectable in the aorta of the kefiran group. Cholesterol contents in stools were almost identical in both groups. Cholesterol content in the liver of the kefiran group was statistically lower than in the control group. Galactose content of βVLDL derived from the kefiran group was higher, and the lipid peroxidation level was much lower than in the control group. RAW264.7 macrophages treated with βVLDL from the kefiran group showed a more spherical shape and accumulated statistically lower cholesterol than macrophages treated with βVLDL from the control group. Orally derived kefiran is absorbed in the blood. Kefiran prevents the onset and development of atherosclerosis in hypercholesterolemic rabbits by anti-inflammatory and anti-oxidant actions.

Detection of inflamed atherosclerotic lesions with diadenosine-5',5'''-P1,P4-tetraphosphate (Ap4A) and positron-emission tomography.

PubMed

Elmaleh, D R; Fischman, A J; Tawakol, A; Zhu, A; Shoup, T M; Hoffmann, U; Brownell, A-L; Zamecnik, P C

2006-10-24

Diadenosine-5',5'''-P(1),P(4)-tetraphosphate (Ap(4)A) and its analog P(2),P(3)-monochloromethylene diadenosine-5',5'''-P(1),P(4)-tetraphosphate (AppCHClppA) are competitive inhibitors of adenosine diphosphate-induced platelet aggregation, which plays a central role in arterial thrombosis and plaque formation. In this study, we evaluate the imaging capabilities of positron-emission tomography (PET) with P(2),P(3)-[(18)F]monofluoromethylene diadenosine-5',5'''-P(1),P(4)-tetraphosphate ([(18)F]AppCHFppA) to detect atherosclerotic lesions in male New Zealand White rabbits. Three to six months after balloon injury to the aorta, the rabbits were injected with [(18)F]AppCHFppA, and microPET imaging showed rapid accumulation of this radiopharmaceutical in the atherosclerotic abdominal aorta, with lesions clearly visible 30 min after injection. Computed tomographic images were coregistered with PET images to improve delineation of aortoiliac tracer activity. Plaque macrophage density, quantified by immunostaining with RAM11 against rabbit macrophages, correlated with PET measurements of [(18)F]AppCHFppA uptake (r = 0.87, P < 0.0001), whereas smooth-muscle cell density, quantified by immunostaining with 1A4 against smooth muscle actin, did not. Biodistribution studies of [(18)F]AppCHFppA in normal rats indicated typical adenosine dinucleotide behavior with insignificant myocardial uptake and fast kidney clearance. The accumulation of [(18)F]AppCHFppA in macrophage-rich atherosclerotic plaques can be quantified noninvasively with PET. Hence, [(18)F]AppCHFppA holds promise for the noninvasive characterization of vascular inflammation.

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

Articular disc and eminence modeling after experimental relocation of the glenoid fossa in growing rabbits.

PubMed

Pirttiniemi, P; Kantomaa, T; Tuominen, M; Salo, L

1994-02-01

The articular surface of the glenoid fossa shows some analogy to the mandibular condyle, since the surface is covered by secondary cartilage, which makes the process more elastic than purely bony structures. The condylar cartilage has been shown to be responsive to alterations in load pressures, and this secondary type of cartilage is also able to increase its proliferative activity to a limited extent when the load pressure is altered. The aim here was to measure changes in proliferative activity and type II collagen secretion in the articular surface of the glenoid fossa after steady experimental posterior relocation of the fossa in the rabbit without actively interfering with normal masticatory action. The shape of the articular disc and interrelations of the joint components were measured macroscopically. Twenty-four five-day-old rabbits underwent gluing of the interparietal, temporoparietal, and lambdoidal sutures. Three experimental and 3 control rabbits were injected with tritiated thymidine at 10, 15, 20, and 30 days and were killed after 2 h for histological, autoradiographic, and immunohistochemical examination. The total number of labeled cells in the proliferative layer near the articular eminence was higher in the experimental group, the difference being greatest in the 15- and 20-day-old rabbits. Immunohistochemical examination revealed less staining for type II collagen on the postero-inferior side of the eminence in the experimental group. The articular disc was flattened in the experimental group, and the elastic tissue bundle connecting the articular eminence and the anterior border of the disc was significantly narrower and longer.

The NF-κB pathway: regulation of the instability of atherosclerotic plaques activated by Fg, Fb, and FDPs.

PubMed

Cao, Yongjun; Zhou, Xiaomei; Liu, Huihui; Zhang, Yanlin; Yu, Xiaoyan; Liu, Chunfeng

2013-11-01

Recently, the molecular mechanism responsible for the instability of atherosclerotic plaques has gradually become a hot topic among researchers and clinicians. Matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) play an important role in the processes of formation and development of atherosclerosis. In this study, we established and employed the transwell co-culture system of rabbit aortic endothelial cells and smooth muscle cells to explore the relationship between fibrin (Fb), fibrinogen (Fg), and/or their degradation products (FDPs) in relation to the instability of atherosclerotic plaques; meanwhile, we observed the effects of Fg, Fb, and FDPs on the mRNA levels of MMPs and VEGF as well as on the activation of nuclear factor-kappa B (NF-κB). We concluded that Fb, Fg, and FDPs are involved in the progression of the instability of atherosclerotic plaques via increasing the expression of MMPs and VEGF. This effect might be mediated by the NF-кB pathway.

Laguerre-based method for analysis of time-resolved fluorescence data: application to in-vivo characterization and diagnosis of atherosclerotic lesions.

PubMed

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

2006-01-01

We report the application of the Laguerre deconvolution technique (LDT) to the analysis of in-vivo time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) data and the diagnosis of atherosclerotic plaques. TR-LIFS measurements were obtained in vivo from normal and atherosclerotic aortas (eight rabbits, 73 areas), and subsequently analyzed using LDT. Spectral and time-resolved features were used to develop four classification algorithms: linear discriminant analysis (LDA), stepwise LDA (SLDA), principal component analysis (PCA), and artificial neural network (ANN). Accurate deconvolution of TR-LIFS in-vivo measurements from normal and atherosclerotic arteries was provided by LDT. The derived Laguerre expansion coefficients reflected changes in the arterial biochemical composition, and provided a means to discriminate lesions rich in macrophages with high sensitivity (>85%) and specificity (>95%). Classification algorithms (SLDA and PCA) using a selected number of features with maximum discriminating power provided the best performance. This study demonstrates the potential of the LDT for in-vivo tissue diagnosis, and specifically for the detection of macrophages infiltration in atherosclerotic lesions, a key marker of plaque vulnerability.

Laguerre-based method for analysis of time-resolved fluorescence data: application to in-vivo characterization and diagnosis of atherosclerotic lesions

NASA Astrophysics Data System (ADS)

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

2006-03-01

We report the application of the Laguerre deconvolution technique (LDT) to the analysis of in-vivo time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) data and the diagnosis of atherosclerotic plaques. TR-LIFS measurements were obtained in vivo from normal and atherosclerotic aortas (eight rabbits, 73 areas), and subsequently analyzed using LDT. Spectral and time-resolved features were used to develop four classification algorithms: linear discriminant analysis (LDA), stepwise LDA (SLDA), principal component analysis (PCA), and artificial neural network (ANN). Accurate deconvolution of TR-LIFS in-vivo measurements from normal and atherosclerotic arteries was provided by LDT. The derived Laguerre expansion coefficients reflected changes in the arterial biochemical composition, and provided a means to discriminate lesions rich in macrophages with high sensitivity (>85%) and specificity (>95%). Classification algorithms (SLDA and PCA) using a selected number of features with maximum discriminating power provided the best performance. This study demonstrates the potential of the LDT for in-vivo tissue diagnosis, and specifically for the detection of macrophages infiltration in atherosclerotic lesions, a key marker of plaque vulnerability.

Laguerre-based method for analysis of time-resolved fluorescence data: application to in-vivo characterization and diagnosis of atherosclerotic lesions

PubMed Central

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

2007-01-01

We report the application of the Laguerre deconvolution technique (LDT) to the analysis of in-vivo time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) data and the diagnosis of atherosclerotic plaques. TR-LIFS measurements were obtained in vivo from normal and atherosclerotic aortas (eight rabbits, 73 areas), and subsequently analyzed using LDT. Spectral and time-resolved features were used to develop four classification algorithms: linear discriminant analysis (LDA), stepwise LDA (SLDA), principal component analysis (PCA), and artificial neural network (ANN). Accurate deconvolution of TR-LIFS in-vivo measurements from normal and atherosclerotic arteries was provided by LDT. The derived Laguerre expansion coefficients reflected changes in the arterial biochemical composition, and provided a means to discriminate lesions rich in macrophages with high sensitivity (>85%) and specificity (>95%). Classification algorithms (SLDA and PCA) using a selected number of features with maximum discriminating power provided the best performance. This study demonstrates the potential of the LDT for in-vivo tissue diagnosis, and specifically for the detection of macrophages infiltration in atherosclerotic lesions, a key marker of plaque vulnerability. PMID:16674179

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

PubMed Central

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

1951-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2017-09-01

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

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.

Ethanolic extract of Artemisia aucheri induces regression of aorta wall fatty streaks in hypercholesterolemic rabbits.

PubMed

Asgary, S; Dinani, N Jafari; Madani, H; Mahzouni, P

2008-05-01

Artemisia aucheri is a native-growing plant which is widely used in Iranian traditional medicine. This study was designed to evaluate the effects of A. aucheri on regression of atherosclerosis in hypercholesterolemic rabbits. Twenty five rabbits were randomly divided into five groups of five each and treated 3-months as follows: 1: normal diet, 2: hypercholesterolemic diet (HCD), 3 and 4: HCD for 60 days and then normal diet and normal diet + A. aucheri (100 mg x kg(-1) x day(-1)) respectively for an additional 30 days (regression period). In the regression period dietary use of A. aucheri in group 4 significantly decreased total cholesterol, triglyceride and LDL-cholesterol, while HDL-cholesterol was significantly increased. The atherosclerotic area was significantly decreased in this group. Animals, which received only normal diet in the regression period showed no regression but rather progression of atherosclerosis. These findings suggest that A. aucheri may cause regression of atherosclerotic lesions.

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

PubMed

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

2014-01-01

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

Detection of inflamed atherosclerotic lesions with diadenosine-5′,5‴-P1,P4-tetraphosphate (Ap4A) and positron-emission tomography

PubMed Central

Elmaleh, D. R.; Fischman, A. J.; Tawakol, A.; Zhu, A.; Shoup, T. M.; Hoffmann, U.; Brownell, A.-L.; Zamecnik, P. C.

2006-01-01

Diadenosine-5′,5‴-P1,P4-tetraphosphate (Ap4A) and its analog P2,P3-monochloromethylene diadenosine-5′,5‴-P1,P4-tetraphosphate (AppCHClppA) are competitive inhibitors of adenosine diphosphate-induced platelet aggregation, which plays a central role in arterial thrombosis and plaque formation. In this study, we evaluate the imaging capabilities of positron-emission tomography (PET) with P2,P3-[18F]monofluoromethylene diadenosine-5′,5‴-P1,P4-tetraphosphate ([18F]AppCHFppA) to detect atherosclerotic lesions in male New Zealand White rabbits. Three to six months after balloon injury to the aorta, the rabbits were injected with [18F]AppCHFppA, and microPET imaging showed rapid accumulation of this radiopharmaceutical in the atherosclerotic abdominal aorta, with lesions clearly visible 30 min after injection. Computed tomographic images were coregistered with PET images to improve delineation of aortoiliac tracer activity. Plaque macrophage density, quantified by immunostaining with RAM11 against rabbit macrophages, correlated with PET measurements of [18F]AppCHFppA uptake (r = 0.87, P < 0.0001), whereas smooth-muscle cell density, quantified by immunostaining with 1A4 against smooth muscle actin, did not. Biodistribution studies of [18F]AppCHFppA in normal rats indicated typical adenosine dinucleotide behavior with insignificant myocardial uptake and fast kidney clearance. The accumulation of [18F]AppCHFppA in macrophage-rich atherosclerotic plaques can be quantified noninvasively with PET. Hence, [18F]AppCHFppA holds promise for the noninvasive characterization of vascular inflammation. PMID:17038498

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

PubMed Central

Chesney, Alan M.; Kemp, Jarold E.

1924-01-01

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

Anti-atherosclerotic effect of Cynodon dactylon extract on experimentally induced hypercholesterolemia in rats

PubMed Central

Pashaie, Belal; Hobbenaghi, Rahim; Malekinejad, Hassan

2017-01-01

Cynodon dactylon (Bermuda grass) is a perennial plant traditionally used as an herbal medicine in many countries. In the present study, anti-atherosclerotic property of ethanolic extract of C. dactylon was investigated in the experimentally induced hypercholesterolemia in rats. In this study, 36 male Wistar rats were selected and allocated into six groups (n = 6). The control group received a normal diet, sham group received a high cholesterol diet (HCD; 1.50% cholesterol and 24.00% fat) and other groups received a HCD and ethanolic extract of C. dactylon at low (100 mg kg-1), moderate (200 mg kg-1) and maximum (400 mg kg-1) doses via gavages. The last group received atorvastatin (10 mg kg-1) through gavage with a HCD. The study period for all groups was six months. At the end of this period, parameters including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were assessed in the blood samples. Additionally, histopathological and immunohistochemical examinations on coronary and aorta arteries sections were performed. The results showed an increase in vessels wall thickness and proliferation of smooth muscle cells in the HCD group, while these pathological changes were not seen in C. dactylon-treated groups. Treatment of HCD animals with C. dactylon positively changed lipid profile by lowering of TC, TG and LDL-C. The results indicate that C. dactylon prevents from early atherosclerotic changes in the vessels wall. PMID:29085605

Anti-atherosclerotic effect of Cynodon dactylon extract on experimentally induced hypercholesterolemia in rats.

PubMed

Pashaie, Belal; Hobbenaghi, Rahim; Malekinejad, Hassan

2017-01-01

Cynodon dactylon (Bermuda grass) is a perennial plant traditionally used as an herbal medicine in many countries. In the present study, anti-atherosclerotic property of ethanolic extract of C. dactylon was investigated in the experimentally induced hypercholesterolemia in rats. In this study, 36 male Wistar rats were selected and allocated into six groups (n = 6). The control group received a normal diet, sham group received a high cholesterol diet (HCD; 1.50% cholesterol and 24.00% fat) and other groups received a HCD and ethanolic extract of C. dactylon at low (100 mg kg -1 ), moderate (200 mg kg -1 ) and maximum (400 mg kg -1 ) doses via gavages. The last group received atorvastatin (10 mg kg -1 ) through gavage with a HCD. The study period for all groups was six months. At the end of this period, parameters including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were assessed in the blood samples. Additionally, histopathological and immunohistochemical examinations on coronary and aorta arteries sections were performed. The results showed an increase in vessels wall thickness and proliferation of smooth muscle cells in the HCD group, while these pathological changes were not seen in C. dactylon -treated groups. Treatment of HCD animals with C. dactylon positively changed lipid profile by lowering of TC, TG and LDL-C. The results indicate that C. dactylon prevents from early atherosclerotic changes in the vessels wall.

TIMP‑3 suppresses the proliferation and migration of SMCs from the aortic neck of atherosclerotic AAA in rabbits, via decreased MMP‑2 and MMP‑9 activity, and reduced TNF‑α expression.

PubMed

Zhai, Huan; Qi, Xun; Li, Zixuan; Zhang, Wei; Li, Chenguang; Ji, Lu; Xu, Ke; Zhong, Hongshan

2018-06-26

The present study investigated the role of tissue inhibitor of matrix metalloproteinase‑3 (TIMP‑3) in regulating the proliferation, migration, apoptosis and activity of matrix metalloproteinase (MMP)‑2 and ‑9, during the development of an atherosclerotic abdominal artery aneurysm (AAA). Experiments were conducted using rabbit AAA neck (NA) smooth muscle cells (SMCs), to investigate the potential for TIMP‑3 to be used as a novel stent coating in preventing aortic dilation adjacent to the AAA. The atherosclerotic AAA model was induced in New Zealand white rabbits via a 6‑week high‑cholesterol diet, followed by incubation of the targeted aortic region with elastase. SMCs were isolated from the aorta adjacent to the aneurysm 30 days after AAA model induction, and stimulated with 3, 10, 30 or 100 ng/ml TIMP‑3. Cell proliferation was investigated using Cell Counting Kit‑8 reagent, migration was examined using a Boyden chamber assay and apoptotic rate was analyzed using the Annexin V‑fluorescein isothiocyanate Apoptosis Detection kit. Gelatin zymography and ELISA were used to measure the activity of MMP‑2 and MMP‑9, and the expression of tumor necrosis factor‑α (TNF‑α), respectively. Analysis of cell proliferation indicated that 10, 30 and 100 ng/ml TIMP‑3 reduced cell viability. Cell migration was decreased by 10, 30 and 100 ng/ml TIMP‑3. MMP‑2 activity was inhibited by 10, 30 and 100 ng/ml TIMP‑3, and MMP‑9 activity was suppressed by 30 and 100 ng/ml TIMP‑3. The protein levels of secreted TNF‑α were reduced by 10, 30 and 100 ng/ml TIMP‑3. The present study demonstrated the ability of 30 and 100 ng/ml TIMP‑3 to attenuate migration and proliferation, and to inhibit the activity of MMP‑2, MMP‑9 and TNF‑α secretion of NA SMCs. In conclusion, TIMP‑3 may be considered a potential therapeutic drug for use in a novel drug‑eluting stent, to attenuate the progressive dilation of the aortic NA.

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.

Erythrocyte membrane cholesterol and lipid core growth in a rabbit model of atherosclerosis: modulatory effects of rosuvastatin.

PubMed

Tziakas, Dimitrios; Chalikias, Georgios; Kapelouzou, Alkistis; Tentes, Ioannis; Schäfer, Katrin; Karayannakos, Panagiotis; Kostakis, Alkiviadis; Boudoulas, Harissios; Konstantinides, Stavros

2013-12-10

Lipid core expansion is partly responsible for the conversion of a stable atherosclerotic lesion to a rupture-prone plaque. Intraplaque hemorrhage contributes to the accumulation of cholesterol within unstable plaques. In the present study, we investigated, using a rabbit model of atherosclerosis, the extent to which diet-induced increases in cholesterol content of erythrocyte membranes (CEM) contribute to lipid core expansion and the modulatory effect of rosuvastatin use. Rabbits fed with atherogenic diet (0.75% cholesterol) for 5 months exhibited advanced atherosclerotic lesions (mean plaque area, 0.39 ± 0.03 mm(2)), and lipid core size was associated with the concentration-time integral (CTI) of CEM levels (r=0.567, P=0.004) independent of other established predictors of lipid core size. Further experiments were performed by feeding rabbits atherogenic diet (1% cholesterol) for 3 months, followed by either normal diet or normal diet plus rosuvastatin for the next 3 months. Although no differences were observed in total plaque area between both groups, administration of rosuvastatin was associated with significantly smaller lipid cores, fewer macrophages within the lipid core, less microvessels as well as with lower CTI of CEM levels compared to normal diet alone. Moreover, intraplaque erythrocyte membranes covered a smaller lipid core area in rabbits under rosuvastatin plus normal diet as opposed to rabbits under diet alone. Increased CEM levels, induced by high-cholesterol diet, are associated with lipid core growth. Ingestion of a potent HMG-CoA reductase inhibitor (rosuvastatin) may decrease CEM levels, and this effect may contribute to regression of the lipid core. © 2013.

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

PubMed Central

Luo, Huilan; Chen, Yongsheng; Wang, Junhua

2010-01-01

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

Increased permeability to polyethylene glycol 4000 in rabbits with experimental colitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Seidman, E.G.; Hanson, D.G.; Walker, W.A.

1986-01-01

Little information is available regarding colonic permeability to macromolecules in health or disease states. In vivo permeability of rabbit colon to (/sup 14/C)polyethylene glycol 4000 (/sup 14/C-PEG) was examined in the presence of immune complex-mediated experimental colitis and compared with that of partially treated (control) and normal rabbits. Permeability was assessed by urinary /sup 14/C-PEG excretion after intrarectal administration of 0.1 mM solution of /sup 14/C-PEG (1 ml/kg, 7.5 X 10(6) cpm/ml). Experimental colitis greatly increased colonic permeability (p less than 0.001 in two-way analysis of variance) compared with control and normal groups (2.06% +/- 0.19%, 0.14% +/- 0.04%, andmore » 0.01% +/- 0.004%, respectively, of rectally administered counts). Gel diffusion chromatography showed that absorbed /sup 14/C-PEG was excreted into urine unchanged, demonstrating its applicability as an inert, nonmetabolizable macromolecular probe. Urinary clearance after mesenteric vein administration of /sup 14/C-PEG was similar in normal animals and animals with colitis, implicating colonic absorption as the source of the group differences. Postmortem histology confirmed the acute colitis lesions in the experimental group. These findings support the hypothesis that nonspecific colonic inflammation is associated with significant alterations of mucosal permeability.« less

Isolation and preliminary characterization of circulating immune complexes from rabbits with experimental syphilis.

PubMed Central

Baughn, R E; Musher, D M

1983-01-01

Immune complexes isolated from sera of rabbits with experimental, disseminated syphilis were found to have sedimentation coefficients greater than 19s. By radioimmunoblot assays, materials precipitated with 2.5% polyethylene glycol or chromatographed on DEAE-Affi-Gel Blue were found to contain albumin, C3, immunoglobulin M (IgM), IgG, and treponemal antigen(s), whereas control materials contained only albumin and IgG. When polyethylene glycol precipitation of immune complexes from syphilitic rabbits was followed by immobilization on protein A and acid elution, radioimmunoblots detected only IgG and treponemal antigen(s). Images PMID:6358025

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

A Quantitative Model of Early Atherosclerotic Plaques Parameterized Using In Vitro Experiments.

PubMed

Thon, Moritz P; Ford, Hugh Z; Gee, Michael W; Myerscough, Mary R

2018-01-01

There are a growing number of studies that model immunological processes in the artery wall that lead to the development of atherosclerotic plaques. However, few of these models use parameters that are obtained from experimental data even though data-driven models are vital if mathematical models are to become clinically relevant. We present the development and analysis of a quantitative mathematical model for the coupled inflammatory, lipid and macrophage dynamics in early atherosclerotic plaques. Our modeling approach is similar to the biologists' experimental approach where the bigger picture of atherosclerosis is put together from many smaller observations and findings from in vitro experiments. We first develop a series of three simpler submodels which are least-squares fitted to various in vitro experimental results from the literature. Subsequently, we use these three submodels to construct a quantitative model of the development of early atherosclerotic plaques. We perform a local sensitivity analysis of the model with respect to its parameters that identifies critical parameters and processes. Further, we present a systematic analysis of the long-term outcome of the model which produces a characterization of the stability of model plaques based on the rates of recruitment of low-density lipoproteins, high-density lipoproteins and macrophages. The analysis of the model suggests that further experimental work quantifying the different fates of macrophages as a function of cholesterol load and the balance between free cholesterol and cholesterol ester inside macrophages may give valuable insight into long-term atherosclerotic plaque outcomes. This model is an important step toward models applicable in a clinical setting.

Effect of intraplaque angiogenesis to atherosclerotic rupture-prone plaque induced by high shear stress in rabbit model

PubMed Central

Qiu, Juhui; Lei, Daoxi; Hu, Jianjun; Yin, Tieying; Zhang, Kang; Yu, Donghong

2017-01-01

Abstract Atherosclerotic prone-rupture plaque is mainly localized in the region of the entrance to the stenosis with high shear stress and the reasons are largely unknown. Our hypothesis is that such a distribution of cells in atherosclerotic plaque may depend on the angiogenesis. Silastic collars induced regions of high shear stress (20.68 ± 5.27 dynes/cm2) in the upstream flow and low shear stress (12.25 ± 1.28 dynes/cm2) in the downstream flow in carotid arteries. Compared with the low shear stress region, plaques in the high shear stress region showed more intraplaque haemorrhaging, less collagen and higher apoptotic rates of vascular smooth muscle cells; endothelial cells (ECs) in the high shear stress region were characterized with integrity and high endothelial nitric oxide synthase (eNOS) expression (1570.3 ± 345.5% vs 172.9 ± 49.9%). The number of intraplaque microvessels is very high in the high shear stress region (15 ± 1.8 n/mm2 vs 3.5 ± 0.4 n/mm2), and the microvessels in the plaque show ECs were abnormal, with membrane blebs, intracytoplasmic vacuoles and leukocyte infiltration. Our current study reveals that the integrity of the endothelium and the vulnerability of atherosclerotic plaques are simultaneously localized in high shear stress regions, and we provide evidence for the first time that microvessels in the intraplaque maybe responsible for rupture-prone plaque formation in the high shear stress region. PMID:28798867

Validation of a time-resolved fluorescence spectroscopy apparatus in a rabbit atherosclerosis model

NASA Astrophysics Data System (ADS)

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

2004-07-01

Time-resolved laser-induced fluorescence spectroscopy (tr-LIFS) has been studied as a potential tool for in vivo diagnosis of atherosclerotic lesions. This study is to evaluate the potential of a compact fiber-optics based tr-LIFS instrument developed in our laboratory for in vivo analysis of atherosclerotic plaque composition. Time-resolved fluorescence spectroscopy studies were performed in vivo on fifteen New Zealand White rabbits (atherosclerotic: N=8, control: N=7). Time-resolved fluorescence spectra were acquired (range: 360-600 nm, increment: 5 nm, total acquisition time: 65 s) from normal aorta wall and lesions in the abdominal aorta. Data were analyzed in terms of fluorescence emission spectra and wavelength specific lifetimes. Following trichrome staining, tissue specimens were analyzed histopathologically in terms of intima/media thickness and biochemical composition (collagen, elastin, foam cells, and etc). Based on intimal thickness, the lesions were divided into thin and thick lesions. Each group was further separated into two categories: collagen rich lesions and foam cell rich lesions based on their biochemical composition. The obtained spectral and time domain fluorescence signatures were subsequently correlated to the histopathological findings. The results have shown that time-domain fluorescence spectral features can be used in vivo to separate atherosclerotic lesions from normal aorta wall as well discrimination within certain types of lesions.

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

Dietary restriction slightly affects glucose homeostasis and delays plasma cholesterol removal in rabbits with dietary lipid lowering.

PubMed

Yu, Qi; Liu, Ruihan; Han, Lijuan; Zhang, Guangwei; Guan, Hua; Pan, Qi; Wang, Siwang; Liu, Enqi

2018-04-15

Dietary restriction (DR) has been reported to promote the beneficial effects on atherosclerotic progression, lipid and glucose metabolism, but little is known about these effects can be enhanced or weakened by dietary lipid lowering. After 12 weeks of the high-cholesterol diet (HCD) feeding, hypercholesterolemic rabbits were fed with either a chow diet ad libitum (AL) or a chow diet with DR for 16 weeks of dietary lipid lowering. Here, we found the DR group exhibited a loss in body weight, small internal organs and the reduced fat mass, but the AL group accumulated more subcutaneous fat than the baseline group. DR treatment slightly worsened glucose tolerance but enhanced insulin sensitivity, and a slight effect of DR on insulin secretion was also observed. After diet cholesterol withdrawal, rabbits showed persistently lowering of total cholesterol and triglyceride in plasma. The DR group had significantly higher plasma total cholesterol than the AL group at the most time points during 7 to 16 weeks of lipid lowering. Although both AL and DR groups developed more severe atherosclerosis than baseline group, DR did not improve atherosclerotic progression and the accumulation of macrophages and smooth muscle cells as well. We concluded that DR affected glucose and lipid metabolism but did not ameliorate atherosclerosis in rabbits when associated with lipid lowering by the dietary cholesterol withdrawal.

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.

Toll-like receptor 7 stimulation by imiquimod induces macrophage autophagy and inflammation in atherosclerotic plaques.

PubMed

De Meyer, Inge; Martinet, Wim; Schrijvers, Dorien M; Timmermans, Jean-Pierre; Bult, Hidde; De Meyer, Guido R Y

2012-05-01

Atherosclerotic plaques tend to rupture as a consequence of a weakened fibrous cap, particularly in the shoulder regions where most macrophages reside. Macrophages express Toll-like receptors to recognize pathogens and eliminate intracellular pathogens by inducing autophagy. Because Toll-like receptor 7 (TLR7) is thought to be expressed in macrophages but not in smooth muscle cells (SMCs), we investigated whether induction of macrophage autophagic death by TLR7 ligand imiquimod can affect the composition of atherosclerotic plaques in favor of their stability. Immunohistochemical staining of human carotid plaques as well as Western blotting of cultured macrophages and SMCs confirmed that TLR7 was expressed in macrophages, but not in SMCs. In vitro experiments showed that only TLR7 expressing cells underwent imiquimod-induced cell death, which was characterized by autophagosome formation. Imiquimod-treated macrophages activated nuclear factor-κB (NF-κB) and released pro-inflammatory cytokines and chemokines. This effect was inhibited by the glucocorticoid dexamethasone. Imiquimod-induced cytokine release was significantly decreased in autophagy-deficient macrophages because these cells died by necrosis at an accelerated pace. Local in vivo administration of imiquimod to established atherosclerotic lesions in rabbit carotid arteries induced macrophage autophagy without induction of cell death, and triggered cytokine production, upregulation of vascular adhesion molecule-1, infiltration of T-lymphocytes, accumulation of macrophages and enlargement of plaque area. Treatment with dexamethasone suppressed these pro-inflammatory effects in vivo. SMCs and endothelial cells in imiquimod-treated plaques were not affected. In conclusion, imiquimod induces macrophage autophagy in atherosclerotic plaques, but stimulates plaque progression through cytokine release and enhanced infiltration of inflammatory cells.

Bisphenol A Exposure Enhances Atherosclerosis in WHHL Rabbits

PubMed Central

Fang, Chao; Ning, Bo; Waqar, Ahmed Bilal; Niimi, Manabu; Li, Shen; Satoh, Kaneo; Shiomi, Masashi; Ye, Ting; Dong, Sijun; Fan, Jianglin

2014-01-01

Bisphenol A (BPA) is an environmental endocrine disrupter. Excess exposure to BPA may increase susceptibility to many metabolic disorders, but it is unclear whether BPA exposure has any adverse effects on the development of atherosclerosis. To determine whether there are such effects, we investigated the response of Watanabe heritable hyperlipidemic (WHHL) rabbits to 400-µg/kg BPA per day, administered orally by gavage, over the course of 12 weeks and compared aortic and coronary atherosclerosis in these rabbits to the vehicle group using histological and morphometric methods. In addition, serum BPA, cytokines levels and plasma lipids as well as pathologic changes in liver, adipose and heart were analyzed. Moreover, we treated human umbilical cord vein endothelial cells (HUVECs) and rabbit aortic smooth muscle cells (SMCs) with different doses of BPA to investigate the underlying molecular mechanisms involved in BPA action(s). BPA treatment did not change the plasma lipids and body weights of the WHHL rabbits; however, the gross atherosclerotic lesion area in the aortic arch was increased by 57% compared to the vehicle group. Histological and immunohistochemical analyses revealed marked increases in advanced lesions (37%) accompanied by smooth muscle cells (60%) but no significant changes in the numbers of macrophages. With regard to coronary atherosclerosis, incidents of coronary stenosis increased by 11% and smooth muscle cells increased by 73% compared to the vehicle group. Furthermore, BPA-treated WHHL rabbits showed increased adipose accumulation and hepatic and myocardial injuries accompanied by up-regulation of endoplasmic reticulum (ER) stress and inflammatory and lipid metabolism markers in livers. Treatment with BPA also induced the expression of ER stress and inflammation related genes in cultured HUVECs. These results demonstrate for the first time that BPA exposure may increase susceptibility to atherosclerosis in WHHL rabbits. PMID:25333893

Direct anti-atherosclerotic therapy; development of natural anti-atherosclerotic drugs preventing cellular cholesterol retention.

PubMed

Orekhov, Alexander N

2013-01-01

The results of numerous clinical trials with statins and other drugs have demonstrated the principal possibility of the prevention and regression of atherosclerosis by pharmacotherapy. This review describes the use of cultured human arterial cells for the mass screening of anti-atherosclerotic substances, the investigation of the mechanisms responsible for their atherosclerosis-related effects, and the optimization of anti-atherosclerotic and anti-atherogenic drug and dietary therapies. Natural products can be considered promising drugs for anti-atherosclerotic therapy. Our basic studies have shown that cellular lipidosis is the principal event in the genesis of atherosclerotic lesions. Using cellular models and natural products, we have developed an approach to prevent lipid accumulation in arterial cells. Based on our knowledge of atherosclerosis, we developed drugs that possess direct anti-atherosclerotic activity. Two-year treatment with allicor (garlic powder) has a direct anti-atherosclerotic effect on carotid atherosclerosis in asymptomatic men. Inflaminat (calendula, elder, and violet), which possesses anti-cytokine activity, has been shown to cause the regression of carotid atherosclerosis following the treatment of asymptomatic men for one year. The phytoestrogen-rich drug karinat (garlic powder, extract of grape seeds, green tea leaves, hop cones, β-carotene, α-tocopherol, and ascorbic acid) prevents the development of carotid atherosclerosis in postmenopausal women. Thus, our basic findings were successfully translated into clinical practice. Because of this translation, a novel approach to antiatherosclerotic therapy was developed. Our clinical trial confirmed the efficacy of both the novel approach and the novel drugs.

In-Vivo Fluorescence Spectroscopy Of Normal And Atherosclerotic Arteries

NASA Astrophysics Data System (ADS)

Deckelbaum, Lawrence I.; Sarembock, Ian J.; Stetz, Mark L.; O'Brien, Kenneth M.; Cutruzzola, Francis W.; Gmitro, Arthur F.; Ezekowitz, Michael D.

1988-06-01

Laser-induced fluorescence spectroscopy can discriminate atherosclerotic from normal arteries in-vitro and may thus potentially guide laser angioplasty. To evaluate the feasibility of laser-induced fluorescence spectroscopy in a living blood-filled arterial system we performed fiberoptic laser-induced fluorescence spectroscopy in a rabbit model of focal femoral atherosclerosis. A laser-induced fluorescence spectroscopy score was derived from stepwise linear regression analysis of in-vitro spectra to distinguish normal aorta (score>0) from atherosclerotic femoral artery (score<0). A 400 u silica fiber, coupled to a helium cadmium laser and optical multichannel analyzer, was inserted through a 5F catheter to induce and record in-vivo fluorescence from femoral and aortoiliac arteries. Arterial spectra could be recorded in all animals (n=10: 5 occlusions, 5 stenoses). Blood spectra were of low intensity and were easily distinguished from arterial spectra. The scores (mean ± SEM) for the in-vivo spectra were -0.69 +/- 0.29 for artherosclerotic femoral, and +0.54 ±. 0.15 for normal aorta (p<.01 p=NS compared to in-vitro spectra). In-vitro, a fiber tip to tissue distance <50 u was necessary for adequate arterial LIFS in blood. At larger distances low intensity blood spectra were recorded (1/20 the intensity of tissue spectra). Thus, fiberoptic laser-induced fluorescence spectroscopy can be sucessfully performed in a blood filled artery provided the fiber tip is approximated to the tissue.

Short communication: Dating components of human atherosclerotic plaques.

PubMed

Gonçalves, Isabel; Stenström, Kristina; Skog, Göran; Mattsson, Sören; Nitulescu, Mihaela; Nilsson, Jan

2010-04-02

Atherosclerotic plaques that give rise to acute clinical symptoms are typically characterized by degradation of the connective tissue and plaque rupture. Experimental studies have shown that mechanisms to repair vulnerable lesions exist, but the rate of remodeling of human plaque tissue has not been studied. In the present study, we determined the biological age of different components of advanced human atherosclerotic plaques by analyzing tissue levels of (14)C released into the atmosphere during the nuclear weapons tests in the late 1950s and early 1960s. Atherosclerotic plaques were obtained from 10 patients (age 46 to 80 years) undergoing carotid surgery. Different regions of the plaques were dissected and analyzed for (14)C content using accelerator mass spectrometry. At the time of surgery, the mean biological age of the cap region was 6.4+/-3.2 years, which was significantly lower than that of the shoulder region (12.9+/-3.0 years, P<0.01), the interface toward the media (12.4+/-3.3 years, P<0.01), and the core (9.8+/-4.5 years, P<0.05). Analysis of proliferative activity and rate of apoptosis showed no signs of increased cellular turnover in the cap, suggesting that the lower (14)C content reflected a more recent time of formation. These results show that the turnover time of human plaque tissue is very long and may explain why regression of atherosclerotic plaque size rarely is observed in cardiovascular intervention trials.

Agmatine ameliorates atherosclerosis progression and endothelial dysfunction in high cholesterol-fed rabbits.

PubMed

El-Awady, Mohammed S; Suddek, Ghada M

2014-06-01

The aim of this work was to explore possible effects of agmatine, an endogenous inhibitor of inducible nitric oxide synthase (iNOS), against hypercholesterolemia-induced lipid profile changes and endothelial dysfunction. Hypercholesterolemia was induced by feeding rabbits with a high-cholesterol diet (HCD, 0.5%) for 8 weeks. Another HCD-fed group was orally administered agmatine (10 mg/kg/day) during weeks 5 through 8. Serum lipid profile, malondialdehyde (MDA), nitric oxide (NO) and lactate dehydrogenase (LDH) were determined. Aorta was isolated to analyse vascular reactivity, atherosclerotic lesions and intima/media (I/M) ratio. HCD induced a significant increase in serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides and high-density lipoprotein cholesterol (HDL-C). Agmatine administration significantly decreased HCD-induced elevations in serum TC and LDL-C, MDA, LDH and NO while significantly increased HDL-C levels. Additionally, agmatine significantly protected against HCD-induced attenuation of rabbit aortic endothelium-dependent relaxation to acetylcholine. HCD and agmatine did not significantly influence aortic endothelium-independent relaxation to sodium nitroprusside. Moreover, agmatine significantly reduced the elevation in aortic atherosclerotic lesion area and I/M ratio. This study is the first to reveal that agmatine has the ability to ameliorate hypercholesterolemia-induced lipemic-oxidative and endothelial function injuries possibly by its antioxidant potential and/or iNOS inhibition. © 2014 Royal Pharmaceutical Society.

Indocyanine Green Enables Near-Infrared Fluorescence Imaging of Lipid-Rich, Inflamed Atherosclerotic Plaques

PubMed Central

Vinegoni, Claudio; Botnaru, Ion; Aikawa, Elena; Calfon, Marcella A.; Iwamoto, Yoshiko; Folco, Eduardo J.; Ntziachristos, Vasilis; Weissleder, Ralph; Libby, Peter; Jaffer, Farouc A.

2011-01-01

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. While molecular imaging agents are available for lower-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 [AU: ok? YES]. Here, we have demonstrated that indocyanine green (ICG), an FDA-approved near-infrared fluorescence (NIRF) emitting compound, targets atheromas within 20 minutes 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 aortae, a vessel of comparable caliber to human coronary arteries. Ex vivo fluorescence reflectance imaging studies 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. PMID:21613624

Cysticercosis in laboratory rabbits.

PubMed

Owiny, J R

2001-03-01

There are no data on the current incidence of Taenia pisiformis in laboratory rabbits. Two cases of cysticercosis most likely due to T. pisiformis in laboratory rabbits (intermediate host) are presented. Both rabbits had no contact with dogs (final host); their caretakers did not work with dogs, and these caretakers changed into facility scrubs and wore gloves when working with the rabbits. Rabbit 1 may have been infected after being fed hay at our facility. In light of the life cycle of the parasite and the history of rabbit 2, it potentially could have been infected prior to arrival at our facility. There have been only three cases of tapeworm cysts in rabbits in our facility (average daily census, 250) during the last 10 years (incidence, < 1%). This report indicates that although cysticercosis is rare in laboratory rabbits, one should always be aware of such incidental findings. Although it may not produce overt illness in the rabbit, hepatic migration could adversely affect the outcome of some experimental procedures

Inflammation in renal atherosclerotic disease.

PubMed

Udani, Suneel M; Dieter, Robert S

2008-07-01

The study of renal atherosclerotic disease has conventionally focused on the diagnosis and management of renal artery stenosis. With the increased understanding of atherosclerosis as a systemic inflammatory process, there has been increased interest in vascular biology at the microvasculature level. While different organ beds share some features, the inflammation and injury in the microvasculature of the kidney has unique elements as well. Understanding of the pathogenesis yields a better understanding of the clinical manifestations of renal atherosclerotic disease, which can be very subtle. Furthermore, identifying the molecular mechanisms responsible for the progression of kidney damage can also direct clinicians and scientists toward targeted therapies. Existing therapies used to treat atherosclerotic disease in other vascular beds may also play a role in the treatment of renal atherosclerotic disease.

Midkine is expressed by infiltrating macrophages in in-stent restenosis in hypercholesterolemic rabbits.

PubMed

Narita, Hiroshi; Chen, Sen; Komori, Kimihiro; Kadomatsu, Kenji

2008-06-01

Neointimal hyperplasia is strikingly suppressed in an endothelium injury model in mice deficient in the growth factor midkine. Knockdown of midkine expression by means of antisense oligonucleotide or small interfering RNA has been shown to lead to suppression of neointimal hyperplasia in a balloon injury model and a rabbit vein graft model; therefore, midkine is an essential factor for neointimal hyperplasia. These findings, however, do not necessarily apply to the function of midkine in vascular stenoses such as in-stent restenosis, because human vascular stenosis is often accompanied by atherosclerosis. We investigated midkine expression in the neointima induced by implantation of a bare metal stent in the atheromatous lesions of hypercholesterolemic rabbits. We analyzed midkine expression during a THP-1 cell differentiation and in peritoneal macrophages exposed to low-density lipoprotein or oxidized low-density lipoprotein. Midkine expression reached the maximum level within 7 days after stenting and was detected in infiltrating macrophages. Differentiation of THP-1 cells to macrophage-like cells did not trigger midkine expression. Neither low-density lipoprotein nor oxidized low-density lipoprotein enhanced midkine expression in peritoneal macrophages that had been activated by thioglycollate, although these cells expressed a significant amount of midkine. The results indicate that macrophages are the major source of midkine in the atherosclerotic neointima. The amount of midkine expressed in macrophages may be sufficient (ie, further enhancement of the expression is not necessary) for the pathogenesis, because oxidized low-density lipoprotein stimulation did not induce the midkine expression. The growth factor midkine is induced during vascular stenosis in mouse and rat models with normal diet. Knockdown of midkine expression suppresses neointimal hyperplasia. The vascular response after stenting differs from that after balloon injury in that the inflammation

Doxycycline Stabilizes Vulnerable Plaque via Inhibiting Matrix Metalloproteinases and Attenuating Inflammation in Rabbits

PubMed Central

Dong, Mei; Zhong, Lin; Chen, Wen Qiang; Ji, Xiao Ping; Zhang, Mei; Zhao, Yu Xia; Li, Li; Yao, Gui Hua; Zhang, Peng Fei; Zhang, Cheng; Zhang, Lei; Zhang, Yun

2012-01-01

Enhanced matrix metalloproteinases (MMPs) activity is implicated in the process of atherosclerotic plaque instability. We hypothesized that doxycycline, a broad MMPs inhibitor, was as effective as simvastatin in reducing the incidence of plaque disruption. Thirty rabbits underwent aortic balloon injury and were fed a high-fat diet for 20 weeks. At the end of week 8, the rabbits were divided into three groups for 12-week treatment: a doxycycline-treated group that received oral doxycycline at a dose of 10 mg/kg/d, a simvastatin-treated group that received oral simvastatin at a dose of 5 mg/kg/d, and a control group that received no treatment. At the end of week 20, pharmacological triggering was performed to induce plaque rupture. Biochemical, ultrasonographic, pathologic, immunohistochemical and mRNA expression studies were performed. The results showed that oral administration of doxycycline resulted in a significant increase in the thickness of the fibrous cap of the aortic plaque whereas there was a substantial reduction of MMPs expression, local and systemic inflammation, and aortic plaque vulnerability. The incidence of plaque rupture with either treatment (0% for both) was significantly lower than that for controls (56.0%, P<0.05). There was no significant difference between doxycycline-treated group and simvastatin-treated group in any serological, ultrasonographic, pathologic, immunohistochemical and mRNA expression measurement except for the serum lipid levels that were higher with doxycycline than with simvastatin treatment. In conclusion, doxycycline at a common antimicrobial dose stabilizes atherosclerotic lesions via inhibiting matrix metalloproteinases and attenuating inflammation in a rabbit model of vulnerable plaque. These effects were similar to a large dose of simvastatin and independent of serum lipid levels. PMID:22737253

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.

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

Pharmacokinetics and atherosclerotic lesions targeting effects of tanshinone IIA discoidal and spherical biomimetic high density lipoproteins.

PubMed

Zhang, Wenli; He, Hongliang; Liu, Jianping; Wang, Ji; Zhang, Suyang; Zhang, Shuangshuang; Wu, Zimei

2013-01-01

High density lipoproteins (HDL) have been successfully reconstructed to deliver a large number of lipophilic drugs. Here, discoidal and spherical recombinant HDL loaded with cardiovascular drug tanshinone IIA (TA) were constructed (TA-d-rHDL and TA-s-rHDL), respectively. And next their in vitro physiochemical and biomimetic properties were characterized. Furthermore, pharmacokinetics, atherosclerotic lesions targeting effects and antiatherogenic efficacies were elaborately performed and compared in atherosclerotic New Zealand White (NZW) rabbits. In vitro characterizations results showed that both TA-d-rHDL and TA-s-rHDL had nano-size diameter, high entrapment efficiency (EE) and drug-loading capacity (DL). Additionally, similar to their native counterparts, TA-d-rHDL maintained remodeling behaviors induced by lecithin cholesterol acyltransferase (LCAT), and TA leaked during remodeling behaviors. Pharmacokinetic studies manifested that both TA-d-rHDL and TA-s-rHDL markedly improved pharmacokinetic behaviors of TA in vivo. Ex vivo imaging demonstrated that both d-rHDL and s-rHDL bound more avidly to atherosclerotic lesions than to normal vessel walls, and s-rHDL had better targeting effect than d-rHDL. Pharmacodynamic tests illustrated that both TA-d-rHDL and TA-s-rHDL had much stronger antiatherogenic efficacies than conventional TA nanostructured lipid carriers (TA-NLC), TA liposomes (TA-L) and commercially available preparation Sulfotanshinone Sodium Injection (SSI). Moreover, TA-s-rHDL had more potent antiatherogenic efficacies than TA-d-rHDL. Collectively our studies indicated that rHDL could be exploited as potential delivery vehicles of TA targeting atherosclerotic lesions as well as synergistically improving efficacies, especially for s-rHDL. Copyright © 2012 Elsevier Ltd. All rights reserved.

Detection of macrophages in atherosclerotic tissue using magnetic nanoparticles and differential phase optical coherence tomography.

PubMed

Oh, Junghwan; Feldman, Marc D; Kim, Jihoon; Sanghi, Pramod; Do, Dat; Mancuso, J Jacob; Kemp, Nate; Cilingiroglu, Mehmet; Milner, Thomas E

2008-01-01

We demonstrate the detection of iron oxide nanoparticles taken up by macrophages in atherosclerotic plaque with differential phase optical coherence tomography (DP-OCT). Magneto mechanical detection of nanoparticles is demonstrated in hyperlipidemic Watanabe and balloon-injured fat-fed New Zealand white rabbits injected with monocrystalline iron oxide nanoparticles (MIONs) of < 40 nm diam. MIONs taken up by macrophages was excited by an oscillating magnetic flux density and resulting nanometer tissue surface displacement was detected by DP-OCT. Frequency response of tissue surface displacement in response to an externally applied magnetic flux density was twice the stimulus frequency as expected from the equations of motion for the nanoparticle cluster.

Dual-wavelength multifrequency photothermal wave imaging combined with optical coherence tomography for macrophage and lipid detection in atherosclerotic plaques using gold nanoparticles

PubMed Central

Wang, Tianyi; Jacob Mancuso, J.; Sapozhnikova, Veronika; Dwelle, Jordan; Ma, Li L.; Willsey, Brian; Shams Kazmi, S. M.; Qiu, Jinze; Li, Xiankai; Asmis, Reto; Johnston, Keith P.; Feldman, Marc D.

2012-01-01

Abstract. The objective of this study was to assess the ability of combined photothermal wave (PTW) imaging and optical coherence tomography (OCT) to detect, and further characterize the distribution of macrophages (having taken up plasmonic gold nanorose as a contrast agent) and lipid deposits in atherosclerotic plaques. Aortas with atherosclerotic plaques were harvested from nine male New Zealand white rabbits divided into nanorose- and saline-injected groups and were imaged by dual-wavelength (800 and 1210 nm) multifrequency (0.1, 1 and 4 Hz) PTW imaging in combination with OCT. Amplitude PTW images suggest that lateral and depth distribution of nanorose-loaded macrophages (confirmed by two-photon luminescence microscopy and RAM-11 macrophage stain) and lipid deposits can be identified at selected modulation frequencies. Radiometric temperature increase and modulation amplitude of superficial nanoroses in response to 4 Hz laser irradiation (800 nm) were significantly higher than native plaque (P<0.001). Amplitude PTW images (4 Hz) were merged into a coregistered OCT image, suggesting that superficial nanorose-loaded macrophages are distributed at shoulders on the upstream side of atherosclerotic plaques (P<0.001) at edges of lipid deposits. Results suggest that combined PTW-OCT imaging can simultaneously reveal plaque structure and composition, permitting characterization of nanorose-loaded macrophages and lipid deposits in atherosclerotic plaques. PMID:22502567

EXPERIMENTAL SYPHILIS IN THE RABBIT

PubMed Central

Brown, Wade H.; Pearce, Louise

1920-01-01

From a study of the phenomena of the primary infection on the one hand, and the phenomena of local spread, or dissemination, on the other, it is seen that a multiplicity of lesions develops in the testicle and scrotum of the rabbit which have much the same characteristics irrespective of their origin. Some of these lesions are clearly recognizable as primary lesions or parts of a primary reaction to infection, while others are just as clearly the results of dissemination of the virus from a primary focus of infection or correspond with lesions which are commonly spoken of as secondary lesions. The effort to draw a sharp line of distinction between these two groups of lesions or between a primary and a secondary stage of infection in the rabbit, however, would be largely an arbitrary procedure. The fact is that the tissues of the scrotum and testicle of the rabbit constitute favorable surroundings for the localization and development of pallidum infections. Under ordinary circumstances, a large part of the reaction to infection which expresses itself in the formation of lesions recognizable by ordinary methods of examination takes place in these tissues. These lesions present certain broad and general characteristics without regard to whether they are primary or secondary in origin; the reaction is merely a reaction to a syphilitic infection which in either case may assume the most diverse character. Further, it would appear that in rabbits infected with such strains of Treponema pallidum as we have used, the virus is never confined to the area occupied by the so called primary lesion, or chancre, but always spreads and always gives rise to a regional adenopathy. There may be no lesions to indicate the progress of this dissemination, but an examination of the inguinal nodes shows that dissemination occurs very soon after inoculation, and a pallidum reaction may be detected in these glands even before infection can be recognized in the scrotum. Subsequently lesions

Effects of induction/inhibition of endogenous heme oxygenase-1 on lipid metabolism, endothelial function, and atherosclerosis in rabbits on a high fat diet.

PubMed

Liu, Danan; He, Zuoyun; Wu, Lirong; Fang, Ying

2012-01-01

The heme oxygenase-1 (HO-1) / carbon monoxide (CO) system has been presumed as a therapeutic target for preventing atherosclerosis. However, the exact mechanism(s) underlying this system remains largely undefined. This study aims to examine the influence of induction/inhibition of HO-1 on atherosclerotic plaque using pharmacological approaches and to elucidate potential mechanisms. Rabbits were randomly assigned to receive a standard diet (control group), high fat diet (HFD), HFD plus HO inducer hemin (HFD + H group), and HFD plus an HO inhibitor, zinc protoporphyrin-9 (ZnPP9, HFD + Z group). Atherosclerotic plaque was evaluated using oil red O staining and histological analyses. Immunohistochemistry, western blotting, and RT-PCR were employed to study the expression of HO-1 and endothelin-1 (ET-1). Levels of CO, nitric oxide (NO), eNOS/iNOS activities, NF-κB activity, and TNF-α level were determined. No significant differences of serum lipid levels were observed among the HFD, HFD + Z, and HFD + H groups. In rabbits, HFD induced typical atherosclerotic plaque and increased intima/media thickness ratio, which was markedly reduced in the HFD + H group and further aggravated in the HFD + Z group. Furthermore, hemin increased HO-1 expression, CO levels, and eNOS activity, while decreasing iNOS levels, ET-1 expression, NF-κB activity, and TNF-α level. ZnPP9 caused opposite effects. Induction of the endogenous HO-1/CO system by hemin can prevent atherosclerosis though increasing CO levels, regulating eNOS activity, NF-κB activity, TNF-α levels, and ET-1 levels in rabbits. Our results add new evidence for the importance of HO-1 in the genesis and development of atherosclerosis and provide several possible mechanisms underlying the anti-atherosclerosis effects of HO-1.

Intracranial Atherosclerotic Disease

PubMed Central

Khan, Maria; Naqvi, Imama; Bansari, Asha; Kamal, Ayeesha Kamran

2011-01-01

Intracranial atherosclerotic disease (ICAD) is the most common proximate mechanism of ischemic stroke worldwide. Approximately half of those affected are Asians. For diagnosis of ICAD, intra-arterial angiography is the gold standard to identify extent of stenosis. However, noninvasive techniques including transcranial ultrasound and MRA are now emerging as reliable modalities to exclude moderate to severe (50%–99%) stenosis. Little is known about measures for primary prevention of the disease. In terms of secondary prevention of stroke due to intracranial atherosclerotic stenosis, aspirin continues to be the preferred antiplatelet agent although clopidogrel along with aspirin has shown promise in the acute phase. Among Asians, cilostazol has shown a favorable effect on symptomatic stenosis and is of benefit in terms of fewer bleeds. Moreover, aggressive risk factor management alone and in combination with dual antiplatelets been shown to be most effective in this group of patients. Interventional trials on intracranial atherosclerotic stenosis have so far only been carried out among Caucasians and have not yielded consistent results. Since the Asian population is known to be preferentially effected, focused trials need to be performed to establish treatment modalities that are most effective in this population. PMID:21772967

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. Copyright © 2016 Elsevier Inc. All rights reserved.

Mechanical properties of human atherosclerotic intima tissue.

PubMed

Akyildiz, Ali C; Speelman, Lambert; Gijsen, Frank J H

2014-03-03

Progression and rupture of atherosclerotic plaques in coronary and carotid arteries are the key processes underlying myocardial infarctions and strokes. Biomechanical stress analyses to compute mechanical stresses in a plaque can potentially be used to assess plaque vulnerability. The stress analyses strongly rely on accurate representation of the mechanical properties of the plaque components. In this review, the composition of intima tissue and how this changes during plaque development is discussed from a mechanical perspective. The plaque classification scheme of the American Heart Association is reviewed and plaques originating from different vascular territories are compared. Thereafter, an overview of the experimental studies on tensile and compressive plaque intima properties are presented and the results are linked to the pathology of atherosclerotic plaques. This overview revealed a considerable variation within studies, and an enormous dispersion between studies. Finally, the implications of the dispersion in experimental data on the clinical applications of biomechanical plaque modeling are presented. Suggestions are made on mechanical testing protocol for plaque tissue and on using a standardized plaque classification scheme. This review identifies the current status of knowledge on plaque mechanical properties and the future steps required for a better understanding of the plaque type specific material properties. With this understanding, biomechanical plaque modeling may eventually provide essential support for clinical plaque risk stratification. Copyright © 2014 Elsevier Ltd. All rights reserved.

Experimental atherosclerosis in rabbits fed cholesterol-free diets.

PubMed

Kritchevsky, D; Tepper, S A; Bises, G; Klurfeld, D M

1982-02-01

Rabbits were fed a semipurified, cholesterol-free atherogenic diet containing 40% sucrose, 25% casein, 14% fat, 15% fiber, 5% salt mix and 1% vitamin mix. The fats were corn oil (CO), palm kernel oil (PO), cocoa butter (CB), and coconut oil (CNO). The rabbits were bled at 3, 6, and 9 months and killed at 9 months. Serum lipids of rabbits fed CO were unaffected. Serum cholesterol levels (mg/dl) at 9 months were: CO -- 64; PO -- 436; CB -- 220; and CNO -- 474. HDL-cholesterol (%) was: CO -- 37; PO -- 8.6; CB -- 25.1; and CNO -- 7.0. Average atherosclerosis (arch + thoracic/2) was: CO -- 0.15; PO -- 1.28; CB -- 0.53; and CNO -- 1.60. Cocoa butter (iodine value 33) is significantly less cholesterolemic and atherogenic than palm oil (iodine value 17) or coconut oil (iodine value 6). The difference between the atherogenic effects of cocoa butter and palm oil may lie in the fact that about half of the fatty acids of palm oil are C 16 or shorter, whereas 76% of the fatty acids of cocoa butter are C 18 or longer.

Rabbit hepatic arterial anatomy variations: implications on experimental design.

PubMed

Tam, Alda L; Melancon, Marites P; Ensor, Joe; Liu, Yang; Dixon, Katherine; McWatters, Amanda; Gupta, Sanjay

2014-12-01

The VX2 rabbit model of liver cancer is commonly used to evaluate the efficacy of locoregional anticancer therapy and knowledge of the hepatic arterial anatomy in the rabbit is important for catheter-directed experiments. To describe the normal anatomy and anatomic variations of the celiac axis and hepatic artery in the rabbit. Angiograms of 222 rabbits were retrospectively reviewed. The branching pattern of the celiac axis was classified and the diameters of the major branches were measured. Paired t-tests were used to compare the difference between the average sizes of arteries. Variant celiac axis or hepatic artery anatomy was noted in 25.9% of angiograms, with the gastric branches arising from the proper hepatic artery in 23.3% of cases. The celiac axis could be successfully classified into one of five distinct branching patterns in 193 (86.9%) cases. The mean diameters of the right and left hepatic arteries were 0.67 mm (95% CI [0.64, 0.7]) and 1.25 mm (95% CI [1.19, 1.31]), respectively. The mean diameters of the medial and lateral branches of the left hepatic artery were 0.63 mm (95% CI [0.6, 0.67]) and 0.91 mm (95% CI [0.86, 0.96]), respectively. The right hepatic artery was significantly smaller than the left hepatic artery and the lateral branch of the left hepatic artery (all P values <0.0001). Arterial variants in the rabbit are not uncommon. The proper hepatic artery often gives origin to gastric artery branches. To facilitate superselective intra-arterial intervention, the left lateral lobe of the liver should be targeted for tumor implantation because of the significant size difference between the right and left hepatic arteries. © The Foundation Acta Radiologica 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

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

PubMed

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

2003-08-01

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

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

PubMed

Shehatou, George S G; Suddek, Ghada M

2016-02-01

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. © 2016 by the Society for Experimental Biology and Medicine.

VENEREAL SPIROCHETOSIS IN AMERICAN RABBITS

PubMed Central

Noguchi, Hideyo

1922-01-01

accomplished through the mating of an infected female with a normal male. The Wassermann reaction was uniformly negative in the five rabbits with spontaneous lesions and in eighteen rabbits experimentally infected. Salvarsan had the same therapeutic effect on the lesions produced by the rabbit spirochete as on the experimental pallidum lesion of the rabbit. The organism belongs to the genus Treponema, and may be designated Treponema cuniculi. PMID:19868615

Proanthocyanidin-rich extract from grape seeds attenuates the development of aortic atherosclerosis in cholesterol-fed rabbits.

PubMed

Yamakoshi, J; Kataoka, S; Koga, T; Ariga, T

1999-01-01

The aim of this study was to evaluate the antiatherosclerotic effect of proanthocyanidin-rich extracts from grape seeds in cholesterol-fed rabbits. Proanthocyanidin-rich extracts (0.1% and 1% in diets [w/w]) did not appreciably affect the changes in serum lipid profile of cholesterol-fed rabbits. The level of cholesteryl ester hydroperoxides (ChE-OOH) induced by 2,2'-azobis(2-amidinopropane-dihydrochloride (AAPH) were lower in the plasma of rabbits fed proanthocyanidin-rich extract plus cholesterol than in the plasma of rabbits fed cholesterol alone, but not in the low-density lipoprotein (LDL). Aortic malondialdehyde (MDA) content decreased in rabbits fed proanthocyanidin-rich extract. Feeding proanthocyanidin-rich extracts (0.1 and 1% in the diet) to rabbits significantly reduced severe atherosclerosis in the aorta. Immunohistochemical analysis revealed a decrease in the number of oxidized LDL-positive macrophage-derived foam cells in atherosclerotic lesions in the aorta of rabbits fed proanthocyanidin-rich extract. When proanthocyanidin-rich extract was administered orally to rats, proanthocyanidin was detected in the plasma by Porters method but not in the lipoproteins (LDL plus VLDL). In an in vitro experiment using human plasma, proanthocyanidin-rich extract added to the plasma inhibited the oxidation of cholesteryl linoleate in LDL, but not in the LDL isolated after the plasma and the extract were incubated in advance. These results suggested that proanthocyanidins, the major polyphenols in red wine, might trap reactive oxygen species in aqueous series such as plasma and interstitial fluid of the arterial wall, thereby inhibiting oxidation of LDL and showing an antiatherosclerotic activity.

Quantifying progression and regression of thrombotic risk in experimental atherosclerosis

PubMed Central

Palekar, Rohun U.; Jallouk, Andrew P.; Goette, Matthew J.; Chen, Junjie; Myerson, Jacob W.; Allen, John S.; Akk, Antonina; Yang, Lihua; Tu, Yizheng; Miller, Mark J.; Pham, Christine T. N.; Wickline, Samuel A.; Pan, Hua

2015-01-01

Currently, there are no generally applicable noninvasive methods for defining the relationship between atherosclerotic vascular damage and risk of focal thrombosis. Herein, we demonstrate methods to delineate the progression and regression of vascular damage in response to an atherogenic diet by quantifying the in vivo accumulation of semipermeable 200–300 nm perfluorocarbon core nanoparticles (PFC-NP) in ApoE null mouse plaques with [19F] magnetic resonance spectroscopy (MRS). Permeability to PFC-NP remained minimal until 12 weeks on diet, then increased rapidly following 12 weeks, but regressed to baseline within 8 weeks after diet normalization. Markedly accelerated clotting (53.3% decrease in clotting time) was observed in carotid artery preparations of fat-fed mice subjected to photochemical injury as defined by the time to flow cessation. For all mice on and off diet, an inverse linear relationship was observed between the permeability to PFC-NP and accelerated thrombosis (P = 0.02). Translational feasibility for quantifying plaque permeability and vascular damage in vivo was demonstrated with clinical 3 T MRI of PFC-NP accumulating in plaques of atherosclerotic rabbits. These observations suggest that excessive permeability to PFC-NP may indicate prothrombotic risk in damaged atherosclerotic vasculature, which resolves within weeks after dietary therapy.—Palekar, R. U., Jallouk, A. P., Goette, M. J., Chen, J., Myerson, J. W., Allen, J. S., Akk, A., Yang, L., Tu, Y., Miller, M. J., Pham, C. T. N., Wickline, S. A., Pan, H. Quantifying progression and regression of thrombotic risk in experimental atherosclerosis. PMID:25857553

The effects of intrathecal nicergoline and nimodipine in cerebral vasospasm: an experimental study in rabbits.

PubMed

Solmaz, Ilker; Onal, Mehmet Bulent; Civelek, Erdinc; Kircelli, Atilla; Ongoru, Onder; Ugurel, Sahin; Erdogan, Ersin; Gonul, Engin

2011-01-01

the aim of this study was to assess and to compare the ability of intrathecal nicergoline and nimodipine in prevention of cerebral vasospasm in a rabbit model of subarachnoid hemorrhage (SAH). twenty male New Zealand white rabbits were allocated into four groups randomly. Subarachnoid hemorrhage was induced by injecting autologous blood into the cisterna magna. The treatment groups were as follows: (1) control [no SAH (n = 5)], (2) SAH only (n = 5), (3) SAH plus nimodipine (n = 5), and (4) SAH plus nicergoline (n = 5). there was a statistically significant difference between the mean basilar artery cross-sectional areas and the mean arterial wall thickness measurements of the control and SAH-only groups (p < 0.05). Basilar artery vessel diameter and luminal section areas in group 3 were significantly higher than in group 2 (p < 0.05). Basilar artery vessel diameter and basilar artery luminal section areas in group 4 were significantly higher than in group 2 (p < 0.05). There was no significant difference between basilar artery vessel diameter and basilar artery luminal section areas in group 3 and group 4. these findings demonstrate that intrathecal nicergoline has a vasodilatatory effect in an experimental model of SAH in rabbits but not more than that of nimodipine.

PET/MRI of Hypoxic Atherosclerosis Using 64Cu-ATSM in a Rabbit Model.

PubMed

Nie, Xingyu; Laforest, Richard; Elvington, Andrew; Randolph, Gwendalyn J; Zheng, Jie; Voller, Tom; Abendschein, Dana R; Lapi, Suzanne E; Woodard, Pamela K

2016-12-01

The macrophage-rich core of advanced human atheroma has been demonstrated to be hypoxic, which may have implications in plaque stability. The goal of this study was to determine the feasibility of the hypoxia PET imaging agent 64 Cu-ATSM to detect hypoxia in a rabbit model of atherosclerosis imaged on a simultaneous PET/MR scanner, using MR for both attenuation correction and depiction of lesion location. New Zealand White rabbits fed a Western diet for 4-6 wk underwent endothelial denudation of the right femoral artery by air desiccation to induce an atherosclerotic-like lesion and underwent a sham operation on the left femoral artery. Four and 8 wk after injury, a 0- to 60-min dynamic whole-body PET/MR examination was performed after injection of approximately 111 MBq of 64 Cu-ATSM. After 24 h, a 0- to 75-min dynamic PET/MR examination after injection of approximately 111 MBq of 18 F-FDG was performed. The rabbits were euthanized, and the injured femoral artery (IF) and sham-operated femoral artery (SF) were collected for immunohistochemistry assessment of hypoxic macrophages (hypoxia marker pimonidazole, macrophage marker RAM-11, and hypoxia-inducible factor-1 α subunit [HIF-1α]). Regions of interest of IF, SF, and background muscle (BM) were drawn on fused PET/MR images, and IF-to-BM and SF-to-BM SUV ratios were compared using the Student t test. Elevated uptake of 64 Cu-ATSM was found in the rabbits' IF compared with the SF. 64 Cu-ATSM imaging demonstrated IF-to-SF SUV mean ratios (±SD) of 1.75 ± 0.21 and 2.30 ± 0.26 at 4 and 8 wk after injury, respectively. 18 F-FDG imaging demonstrated IF-to-SF SUV mean ratios of 1.84 ± 0.12 at 8 wk after injury. IF-to-BM SUV mean ratios were significantly higher (P < 0.001) than SF-to-BM SUV mean ratios both 4 and 8 wk after injury for 64 Cu-ATSM and 8 wk after injury for 18 F-FDG (P < 0.05). Pimonidazole immunohistochemistry at 8 wk colocalized to RAM-11 and HIF-1α. The results show that hypoxia is present in this

Electroacupuncture analgesia in a rabbit ovariohysterectomy.

PubMed

Parmen, Valentin

2014-02-01

This study investigated the effectiveness of electroacupuncture analgesia (EAA) at local and paravertebral acupoints for a rabbit undergoing an ovariohysterectomy. Twelve clinically healthy New Zealand white rabbits were chosen and divided into two groups: the control group (5 rabbits) and the experimental group (7 rabbits). A neuroleptanalgesic (ketamine + xylazine) was administered to the control group (NLA group); the experimental group received EAA treatment (EAA group). The EAA treatment includes one acupuncture formula for local stimulation at the incision site and systemic stimulation. Results of clinical research have shown postoperative analgesia using EAA treatment to be superior to that using NLA. The average postoperative recovery time was 5.2 times longer in the NLA group than in the EAA group. Because consciousness was maintained, EAA presented an advantage in thermoregulation. Animals administered NLA had prolonged thermal homeostasis because of neurovegetative disconnection. For the EAA group, the operative times were characterized as excellent (28%, p = 0.28) or good (72%, p = 0.72). Local stimulation at the incision site provided excellent analgesia of the abdominal wall (100%). In conclusion, EA can provide general analgesia with a considerable analgesic effect for a rabbit undergoing an ovariohysterectomy, resulting in a short postoperative recovery time. Copyright © 2014. Published by Elsevier B.V.

Intra-plaque production of platelet-activating factor correlates with neoangiogenesis in human carotid atherosclerotic lesions.

PubMed

Lupia, Enrico; Pucci, Angela; Peasso, Paolo; Merlo, Maurizio; Baron, Paolo; Zanini, Cristina; Del Sorbo, Lorenzo; Rizea-Savu, Simona; Silvestro, Luigi; Forni, Marco; Emanuelli, Giorgio; Camussi, Giovanni; Montrucchio, Giuseppe

2003-09-01

Platelet-activating factor (PAF) is a phospholipid mediator synthesized by activated inflammatory and endothelial cells. Recently PAF has been shown to contribute to neoangiogenesis in several experimental models. Here we evaluated the presence of PAF and its potential role in neovascularization within human atherosclerotic plaques. The amount of PAF extracted from 18 carotid plaques (266.65+/-40.07 pg/100 mg dry tissue; mean +/- SE) was significantly higher than that extracted from 18 normal arterial specimens (6 from carotid artery and 12 from aorta) (4.72+/-2.31 pg/100 mg dry tissue; mean +/- SE). The levels of PAF significantly correlated with the infiltration of CD68-positive monocytes and the extent of neovascularization, detected as von Willebrand Factor-positive cells. The amount of PAF also correlated with the area occupied by TNF-alpha-expressing cells. The absence of enhanced level of PAF in the circulation of atherosclerotic patients suggests a local production of this mediator within the plaque. The lipid extracts of atherosclerotic plaques containing high levels of PAF-bioactivity, but not those of control arteries, were angiogenic in a murine Matrigel model. WEB 2170, a specific PAF receptor antagonist, significantly prevented angiogenesis induced by the lipid extracts of atherosclerotic plaques. Our results indicate a local production of PAF within the atherosclerotic plaques and suggest that it may contribute to intra-plaque neoangiogenesis.

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. Copyright © 2016 Elsevier B.V. All rights reserved.

From anatomy to function: diagnosis of atherosclerotic renal artery stenosis.

PubMed

Odudu, Aghogho; Vassallo, Diana; Kalra, Philip A

2015-12-01

Atherosclerotic renal artery stenosis (ARAS) affects 7% of the over 65 s and will be increasingly common with an ageing population. ARAS obstructs normal renal perfusion with adverse renal and cardiovascular consequences. Drug therapy is directed at reducing atherosclerotic risk. Two recent major trials of revascularization for ARAS showed that clinical outcomes were not improved beyond those offered by optimal drug therapy in most patients. This reflects experimental data showing that restoration of blood flow alone may not attenuate a cascade of tissue injury. A shift from anatomic to functional imaging of ARAS coupled to novel therapies might improve clinical outcomes in selected patients. This review outlines the case for separately assessing hemodynamic significance of arterial stenosis and functional reserve of renal parenchymal tissue. The authors consider current and emerging diagnostic techniques for ARAS and their potential to allow individualized and functionally directed treatments.

Effects of local gene transfer of VEGF on neointima formation after balloon injury in hypercholesterolemic rabbits

PubMed Central

Dulak, Jozef; Schwarzacher, Severin P; Zwick, Ralf H; Alber, Hannes; Millonig, Gunda; Weiss, Caecilia; Hügel, Heike; Frick, Matthias; Jozkowicz, Alicja; Pachinger, Otmar; Weidinger, Franz

2006-01-01

Enhancement of the generation of nitric oxide (NO) and vascular endothelial growth factor (VEGF) are suggested to prevent restenosis after angioplasty. Accordingly, we tested whether the local delivery of l-arginine (l-Arg), a substrate for NO generation and the VEGF gene, alone or in combination, can influence neointima formation in hypercholesterolemic rabbits. Balloon injury of the iliac arteries was performed in 24 New Zealand White rabbits fed a 1% cholesterol diet for 3 weeks followed by a local infusion of: (1) pSG5VEGF165 plasmid alone (1000 μg); (2) pSG5VEGF165 (1000 μg) with l-Arg (800 mg); (3) l-Arg (800 mg) alone; and (4) l-Arg (800 mg) with naked pSVβ-gal plasmid (1000 μg). The animals were kept on the hypercholesterolemic diets for a further 28 days, when vessels were taken for morphometric analysis and immunocytochemistry. Endogenous rabbit VEGF concentration in the plasma increased significantly at 7 days after injury (17.06 ± 1.57 vs 23.01 ± 1.9 pg/ml; p < 0.02) and remained elevated for up to 28 days (28.46 ± 5.24; p < 0.01). Injured arteries exhibited strong immunocytochemical staining for rabbit VEGF. Rabbits that received a VEGF gene transfer revealed more prominent neointima formation, whereas treatment with l-Arg was associated with significantly less intimal thickness (p < 0.05). Local transfer of the VEGF gene does not inhibit neointima formation in hypercholesterolemic rabbits. Our results suggest that VEGF gene therapy applied locally in atherosclerotic arteries may not be beneficial. PMID:16444857

The influence of systemically administered oxytocin on the implant-bone interface area: an experimental study in the rabbit

PubMed Central

Cho, Sung-Am; Park, Sang-Hun

2014-01-01

PURPOSE The purpose of this study was to assess the effect of systemically administered oxytocin (OT) on the implant-bone interface by using histomorphometric analysis and the removal torque test. MATERIALS AND METHODS A total of 10 adult, New Zealand white, female rabbits were used in this experiment. We placed 2 implants (CSM; CSM Implant, Daegu, South Korea) in each distal femoral metaphysis on both the right and left sides; the implants on both sides were placed 10 mm apart. In each rabbit, 1 implant was prepared for histomorphometric analysis and the other 3 were prepared for the removal torque test (RT). The animals received intramuscular injections of either saline (control group; 0.15 M NaCl) or OT (experimental group; 200 µg/rabbit). The injections were initiated on Day 3 following the implant surgery and were continued for 4 subsequent weeks; the injections were administered twice per day (at a 12-h interval), for 2 days per week. RESULTS While no statistically significant difference was observed between the two groups (P=.787), the control group had stronger removal torque values. The serum OT concentration (ELISA value) was higher in the OT-treated group, although no statistically significant difference was found. Further, the histomorphometric parameter (bone-toimplant contact [BIC], inter-thread bone, and peri-implant bone) values were higher in the experimental group, but the differences were not significant. CONCLUSION We postulate that OT supplementation via intramuscular injection weakly contributes to the bone response at the implant-bone interface in rabbits. Therefore, higher concentrations or more frequent administration of OT may be required for a greater bone response to the implant. Further studies analyzing these aspects are needed. PMID:25551011

Atherosclerotic Cardiovascular Disease Beginning in Childhood

PubMed Central

2010-01-01

Although the clinical manifestations of cardiovascular disease (CVD), such as myocardial infarction, stroke, and peripheral vascular disease, appear from middle age, the process of atherosclerosis can begin early in childhood. The early stage and progression of atherosclerosis in youth are influenced by risk factors that include obesity, hypertension, dyslipidemia, and smoking, and by the presence of specific diseases, such as diabetes mellitus and Kawasaki disease (KD). The existing evidence indicates that primary prevention of atherosclerotic disease should begin in childhood. Identification of children at risk for atherosclerosis may allow early intervention to decrease the atherosclerotic process, thereby preventing or delaying CVD. This review will describe the origin and progression of atherosclerosis in childhood, and the identification and management of known risk factors for atherosclerotic CVD in children and young adults. PMID:20111646

Immunogenicity of Phleum pratense depigmented allergoid vaccines: experimental study in rabbits.

PubMed

Iraola, V; Gallego, M T; López-Matas, M A; Morales, M; Bel, I; García, N; Carnés, J

2012-01-01

Immunogenicity studies are based on accurate preclinical and clinical assessment of pharmaceutical products. The immunogenicity of modified allergen vaccines has not been fully elucidated, and the mechanisms involved are not well understood. Animal and human models have recently shown that depigmented allergoids induce specific immunoglobulin (Ig) G against individual allergens, thus supporting the clinical efficacy of these vaccines. The aim of this study was to investigate the production of specific IgG against individual antigens and their isoforms in rabbits injected with depigmented allergoid extracts of Phleum pratense pollen. Two New Zealand rabbits were immunized with depigmented-polymerized extracts adsorbed onto aluminum hydroxide (Depigoid) of P pratense. Rabbits were injected 3 times (35 microg Phl p 5). Specific IgG titers against native, depigmented, and depigmented-polymerized extracts and individual allergens (rPhl p 1 and rPhl p 5a) were analyzed by direct enzyme-linked immunosorbent assay. The capacity of these synthesized antibodies to recognize individual native and depigmented allergens and different isoforms was evaluated by immunoblot and 2-D analysis. All rabbits produced high titers of specific IgG against the 3 extracts. Rabbits injected with depigmented allergoids produced similar specific antibody titers against native, depigmented, and depigmented-polymerized extracts. Serum samples recognized individual allergens and their isoforms in the nonmodified extracts. Vaccines containing depigmented allergoid extracts of P pratense induce immunogenicity in vivo. The antibodies produced after injection of these extracts clearly recognized allergens and different isoforms in their native configuration.

ACE2 activity was increased in atherosclerotic plaque by losartan: Possible relation to anti-atherosclerosis.

PubMed

Zhang, Yue Hui; Hao, Qing Qing; Wang, Xiao Yu; Chen, Xu; Wang, Nan; Zhu, Li; Li, Shu Ying; Yu, Qing Tao; Dong, Bo

2015-06-01

Angiotensin-converting enzyme 2 (ACE2) is a new member of the renin-angiotensin system (RAS) and it has been proposed that ACE2 is a potential therapeutic target for the control of cardiovascular disease. The effect of losartan on the ACE2 activity in atherosclerosis was studied. Atherosclerosis was induced in New Zealand white rabbits by high-cholesterol diet for 3 months. An Angiotensin II (Ang II) receptor blocker (losartan, 25 mg/kg/d) was given for 3 months. ACE2 activity was measured by fluorescence assay and the extent of atherosclerosis was evaluated by H&E and Oil Red O staining. In addition, the effect of losartan on ACE2 activity in smooth muscle cells (SMCs) in vitro was also evaluated. Losartan increased ACE2 activity in atherosclerosis in vivo and SMCs in vitro. Losartan inhibited atherosclerotic evolution. Addition of losartan blocked Ang II-induced down-regulation of ACE2 activity, and blockade of extracellular signal-regulated kinase (ERK1/2) with PD98059 prevented Ang II-induced down-regulation of ACE2 activity. The results showed that ACE2 activity was regulated in atherosclerotic plaque by losartan, which may play an important role in treatment of atherosclerosis. The mechanism involves Ang II-AT1R-mediated mitogen-activated protein kinases, MAPKs (MAPKs) signaling pathway. © The Author(s) 2014.

Imaging of oxidation-specific epitopes with targeted nanoparticles to detect high-risk atherosclerotic lesions: Progress and future directions

PubMed Central

Briley-Saebo, Karen; Yeang, Calvin; Witztum, Joseph L.; Tsimikas, Sotirios

2014-01-01

Oxidation-specific epitopes (OSE) within developing atherosclerotic lesions are key antigens that drive innate and adaptive immune responses in atherosclerosis, leading to chronic inflammation. Oxidized phospholipids and malondialdehyde-lysine epitopes are well-characterized OSE present in human atherosclerotic lesions, particularly in pathologically defined vulnerable plaques. Using murine and human OSE-specific antibodies as targeting agents, we have developed radionuclide and magnetic resonance based nanoparticles, containing gadolinium, manganese or lipid-coated ultrasmall superparamagnetic iron oxide, to noninvasively image OSE within experimental atherosclerotic lesions. These methods quantitate plaque burden, allow detection of lesion progression and regression, plaque stabilization, and accumulation of OSE within macrophage-rich areas of the artery wall, suggesting they detect the most active lesions. Future studies will focus on using “natural” antibodies, lipopeptides and mimotopes for imaging applications. These approaches should enhance the clinical translation of this technique to image, monitor, evaluate efficacy of novel therapeutic agents and guide optimal therapy of high-risk atherosclerotic lesions. PMID:25297940

Effect of Porcine Chondrocyte-Derived Extracellular Membrane (CDECM) on Postoperative Wound Healing in an Experimental Rabbit Model of Glaucoma Filtration Surgery.

PubMed

Kim, Jung Lim; Lee, Hye Sook; Lee, Yoonjin; Kang, Mi Seon; Lee, Sang Joon; Yang, Jae Wook

2017-06-01

We investigated whether a chondrocyte-derived extracellular membrane (CDECM) could reduce postoperative scar formation in an experimental rabbit model of glaucoma filtration surgery. Thirty-six male New Zealand white rabbits underwent experimental glaucoma filtration surgeries on the right eye and were randomly divided into the following two treatment groups: the CDECM group was treated with subconjunctival injections of 0.1ml CDECM (25 mg/ml; n = 18 eyes), and the operation (OP) group was treated with subconjunctival injections of 0.1 ml balanced salt solution (n = 18 eyes). The left eyes were used as controls (n = 36 eyes). The effects of the CDECM on the experimental rabbit model were investigated using histopathological, immunochemical analyses and Western blotting analyses of the inflammation, fibrosis and angiogenesis. On the 14th postoperative day, the eyes of the CDECM group displayed reduced vascularity and fibrosis compared with the OP group. The vascular endothelial growth factor (VEGF), CD31 and TNFβ immunostaining were also reduced in the CDECM group. The level of TNFα mRNA was increased in the OP group. On the 28th postoperative day, the eyes of the CDECM group also exhibited reduced vascularity and less inflammation and fibrosis than those of the OP group. The expressions of VEGF, CD31, macrophage, TNFβ and NF-κB p65 were also decreased in the CDECM group. The levels of TNFα mRNA significantly differ, and the level of matrix metallopeptidase 9 (MMP9) was increased in the OP group. To determine the specific upstream pathway that was associated with NF-κB activation due to glaucoma filtration surgery, we measured Akt, PKCs and MAPKs signaling. The phosphorylation of p38 MAPK was increased in the OP group, whereas this expression was decreased by CDECM treatment. CDECM seems to suppress angiogenesis, inflammation and fibrosis, which were related to wound healing in the experimental rabbit model of glaucoma filtration surgery. This effect

Detection and characterization of early plaque formations by Raman probe spectroscopy and optical coherence tomography: an in vivo study on a rabbit model

NASA Astrophysics Data System (ADS)

Matthäus, Christian; Dochow, Sebastian; Egodage, Kokila D.; Romeike, Bernd F.; Brehm, Bernhard R.; Popp, Jürgen

2018-01-01

Intravascular imaging techniques provide detailed specification about plaque appearance and morphology, but cannot deliver information about the biochemical composition of atherosclerotic plaques. As the biochemical composition is related to the plaque type, important aspects such as the risk of a plaque rupture and treatment are still difficult to assess. Currently, various spectroscopic techniques are tested for potential applications for the chemical analysis of plaque depositions. Here, we employ Raman spectroscopy in combination with optical coherence tomography (OCT) for the characterization of plaques on rabbits in vivo. Experiments were carried out on New Zealand white rabbits treated with a fat- and cholesterol-enriched diet, using a Raman probe setup with a 785-nm multimode laser as an excitation source. Subsequently, OCT images were acquired with a swept source at 1305±55 nm at 22.6 mW. Raman spectra were recorded from normal regions and regions with early plaque formations. The probe positioning was monitored by x-ray angiography. The spectral information identified plaque depositions consisting of lipids, with triglycerides as the major component. Afterward, OCT images of the spectroscopically investigated areas were obtained. The spectral information correlates well with the observed intravascular morphology and is in good agreement with histology. Raman spectroscopy can provide detailed biochemical specification of atherosclerotic plaques.

Lipoicmethylenedioxyphenol Reduces Experimental Atherosclerosis through Activation of Nrf2 Signaling

PubMed Central

Ying, Zhekang; Chen, Minjie; Xie, Xiaoyun; Wang, Xiaoke; Kherada, Nisharahmed; Desikan, Rajagopal; Mihai, Georgeta; Burns, Patrick; Sun, Qinghua; Rajagopalan, Sanjay

2016-01-01

Objective Oxidative stress is implicated in the pathogenesis of atherosclerosis, and Nrf2 is the transcriptional factor central in cellular antioxidant responses. In the present study, we investigate the effect of a dihydrolipoic acid derivative lipoicmethylenedioxyphenol (LMDP) on the progression of atherosclerosis and test whether its effect on atherosclerosis is mediated by Nrf2. Methods and Results Both magnetic resonance imaging (MRI) scanning and en face analysis reveal that 14 weeks of treatment with LMDP markedly reduced atherosclerotic burden in a rabbit balloon vascular injury model. Myograph analyses show decreased aortic contractile response to phenylephrine and increased aortic response to acetylcholine and insulin in LMDP-treated animals, suggesting that LMDP inhibits atherosclerosis through improving vascular function. A role of Nrf2 signaling in mediating the amelioration of vascular function by LMDP was supported by increased Nrf2 translocation into nuclear and increased expression of Nrf2 target genes. Furthermore, chemotaxis analysis with Boydem chamber shows that leukocytes isolated from LMDP-treated rabbits had reduced chemotaxis, and knock-down of Nrf2 significantly reduced the effect of LMDP on the chemotaxis of mouse macrophages. Conclusion Our results support that LMDP has an anti-atherosclerotic effect likely through activation of Nrf2 signaling and subsequent inhibition of macrophage chemotaxis. PMID:26859892

Introduction of Lens-angle Reconstruction Surgery in Rabbit Eyes

PubMed Central

Kim, Min Hee; Hwang, Ho Sik; Park, Kyoung Jin; Hwang, Je Hyung

2014-01-01

Purpose In this study, we examined the stability of the lens-angle supporter (LAS) for accommodation restoration by comparing intraocular lens (IOL) location, after-cataract and ciliary body damage after cataract surgery in rabbits. Methods Eight rabbits were divided into experimental and control groups of four rabbits each. Phacoemulsification and irrigation and aspiration were performed in all rabbits. This was followed by an LAS and IOL insertion in the four experimental rabbits. In the four control rabbits, only an IOL insertion was performed. Six months after the surgery, the location of the IOL, the conditions of the lens capsule and ciliary body were evaluated using a slitl-amp examination and Miyake-Apple view. Results For the experimental group, the ultrasound biomicroscope results showed normal LAS and IOL positioning in all four cases. According to the slitlamp examination and Miyake-Apple view, the IOL was positioned at the center, with less after-cataract and damage to the ciliary body. For the control group, ultrasound biomicroscope results indicated a higher IOL position than normal, as well as a single case of IOL decentering. According to the slit-lamp examination and Miyake-Apple view, the IOL was decentered with more severe after-cataract and ciliary body damage. Conclusions The LAS has the potential to maintain a stable IOL position while producing less after-cataract when used in lens-angle reconstruction for correction of presbyopia. Moreover, LAS implantation incurs less damage to the ciliary body. PMID:25435752

Dealcoholized red wine containing known amounts of resveratrol suppresses atherosclerosis in hypercholesterolemic rabbits without affecting plasma lipid levels.

PubMed

Wang, Zhirong; Zou, Jiangang; Cao, Kejiang; Hsieh, Tze-Chen; Huang, Yuanzhu; Wu, Joseph M

2005-10-01

Moderate consumption of red wine is associated with a reduced risk of coronary heart disease (CHD). This phenomenon is based on data from epidemiological observations known as the French paradox, and has been attributed to CHD-protective phytochemicals, e.g. resveratrol in red wine. Since red wine also contains alcohol, it is conceivable that alcohol interacts with resveratrol to elicit the observed cardioprotective effects. To determine whether resveratrol has alcohol-independent affects, we compared cardioprotective properties of dealcoholized Chinese red wine with alcohol-containing Chinese red wine having comparable amounts of resveratrol, using a hypercholesterolemic rabbit model and resveratrol as a reference. Animals fed a high cholesterol (1.5%) diet were simultaneously given water containing resveratrol (3 mg/kg/day) or red wine (4 ml/kg/day) containing 3.98 mg/l and 3.23 mg/l resveratrol for regular and dealcoholized red wine, respectively, for a 12-week duration. Total, HDL- and LDL-cholesterol and triglyceride levels in the plasma were measured before and after the cholesterol challenge. Atherosclerotic plaques in the thoracic aorta were evaluated using histochemical methods. Vascular and endothelial functions in the femoral artery were also assessed by ultrasonographic image analysis. High cholesterol-fed animals showed a significant increase in plasma levels of total, HDL- and LDL-cholesterol, but not triglycerides, compared to those fed a regular diet. Dietary cholesterol-elicited lipid changes were similarly observed in animals concurrently fed dealcoholized red wine, red wine or resveratrol. In contrast, whereas atherosclerotic lesions were clearly evident in specimens prepared from the thoracic aorta of high cholesterol-fed animals, the size, density, and mean area of atherosclerotic plaques, and thickness of the intima layer were significantly reduced in rabbits given dealcoholized red wine, red wine, or resveratrol. These results were in

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.

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

The acaricidal efficacy of aqueous neem extract and ivermectin against Sarcoptes scabiei var. cuniculi in experimentally infested rabbits.

PubMed

Seddiek, Shaker A; Khater, Hanem F; El-Shorbagy, Mohamed M; Ali, Ali M

2013-06-01

Sarcoptes scabiei var. cuniculi is one of the most important veterinary ectoparasites in rabbits and results in considerable loss of weight, productivity, and wool quality. The acaricidal activity of aqueous leaf extract of neem (CAN) and ivermectin (IVR) were evaluated in vitro and in vivo against S. scabiei var. cuniculi. Rabbits were classified into four groups (ten rabbits each). The first group (group 1) was designated as the negative control group. Each rabbit of the other groups was experimentally infested with 50 mites. One month post-infestation, the second group (group 2) was not treated and taken into account as the positive control group. The third group (group 3) was subcutaneously injected with 1 % IVR (200 μg/kg body weight, three times within a week interval). The fourth group (group 4) was treated topically with CAN (25 %) every 3 days for three consecutive weeks. Index scoring of lesions was described weekly. The number of live mites (larvae, nymphs, and adults) on each rabbit was counted on the 14th, 28th, and 42th day post-treatment (PT). Blood samples were taken 28 and 42 days PT for estimation of some chemical parameters. The body weight and cumulative body weight gain were recoded 14, 28, and 42 days PT. CAN (40 %) was highly efficacious against larvae of S. scabiei var. cuniculi as 100 % mortality was reached 24 h PT. On the other hand, all treated mites with CAN (20 %) and IVR died 48 h PT. The lethal values of CAN (LC50, LC90, LC95, and LC99) were 7.496, 14.67, 17.75, and 25.37 %, respectively, 48 h PT. Lesion scoring in groups 3 and 4 were significantly decreased (P ≤ 0.05), reaching 0.20 and 0.40, respectively, when compared with that of group 2 (4.00), 42 days PT. Twenty-eight days PT, the reduction percentages of mites infesting rabbits were 93.38 and 93.09 % for IVR and CAN, respectively. However, complete mite reduction was reached 42 days PT. Rabbits treated with CAN did not show signs of restlessness or

[Protective effect of Helianthus annuus (sunflower) on myocardial infarction in New Zealand rabbit].

PubMed

Guardia-Espinoza, Edith; Herrera-Hurtado, Gianina Liseth del Carmen; Garrido-Jacobi, Saúl; Cárdenas-Peralta, Danitza; Martínez-Romero, Christian; Hernández-Figueroa, Pedro; Condori-Calizaya, Mary; La Barrera-Llacchua, Juan; Flores-Ángeles, Miguel

2015-01-01

Determine the protective effect of oil Helianthus annuus (Sunflower) on myocardial infarction induced by epinephrine in New Zealand rabbits. The rabbits were randomized into five groups (8 per group): blank, negative control, experimental 1 (10 mg / kg), experimental 2 (20 mg / kg) and three experimental (40 mg/ kg). Experimental groups 1, 2 and 3 received Helianthus annuus oil for two weeks. Epinephrine (2 mg/Kg) to the negative, Experimental Control 1, 2 and 3 groups was given over two consecutive days with an interval of 24 h after pretreatment with oil. Twenty four hours after the last administration, the rabbits were anesthetized and sacrificed. Serum troponin I and polymorphonuclear evaluated by .mu.m.sup.2. Significant difference between the negative control group and the experimental groups 1, 2 and 3 was found in the serum variables troponin I and polymorphonuclear by .mu.m.sup.2. Helianthus annuus oil at doses of 20 mg/kg has protective effect on myocardial infarction induced by epinephrine in New Zealand rabbits.

Vitamin E prevents steroid-induced osteonecrosis in rabbits

PubMed Central

Kuribayashi, Masaaki; Takahashi, Kenji A; Arai, Yuji; Ishida, Masashi; Goto, Tsuyoshi; Kubo, Toshikazu

2010-01-01

Background and purpose Prevention of osteonecrosis after corticosteroid administration would be important. We examined the potential of vitamin E (α-tocopherol) to reduce the incidence of corticosteroid-induced osteonecrosis in an animal model. Methods Japanese white rabbits were divided into 2 groups; the control group was fed a normal diet and the experimental group was fed α-tocopherol-supplemented diet in which α-tocopherol (600 mg/kg diet) was added to the normal diet. To induce osteonecrosis, high-dose methylprednisolone acetate (MPSL) (20 mg/kg body weight) was injected once into the right gluteus medius muscle of all rabbits. 4 weeks after the injection of MPSL, the presence or absence of osteonecrosis of bilateral femurs was examined histopathologically. The tocopherol/cholesterol ratios were calculated. The plasma levels of thiobarbituric acid-reactive substances (TBARS) were measured. Results Alpha-tocopherol-supplemented diet reduced the incidence of osteonecrosis, which developed in 14 of 20 rabbits in the control group and 5 of 21 rabbits in the experimental group (p = 0.004). The tocopherol/cholesterol ratio was higher in the experimental group than in the control group after the α-tocopherol administration. The plasma TBARS level was lower in the experimental group than in the control group at 4 weeks after the MPSL administration. Interpretation Our findings may offer a new approach for the prevention of corticosteroid-induced osteonecrosis. PMID:20146637

[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. Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.

Experimental study on skin irritation of bone spur powder on rabbit

NASA Astrophysics Data System (ADS)

Ma, Zhenzhen; Zhang, Xuhui; Hao, Shaojun; Shen, Huiling; Wang, Huamin; Ji, Xianghui; Zhang, Zhengchen; Huang, Youling

2018-04-01

To observe the effect of bone powder of rabbit skin, provide the basis for the safety of clinical use of bone powder, 24 rabbits were randomly divided into 6 groups, complete skin test and damaged skin test each divided into 3 groups (n=4), high, low, 3 doses tested daily administered 1 times, continuous administration for 7 days, in 24 hours after the last administration of drug residues, wash with warm water, the removal of L hours after drug for 24 hours, 48 hours, 72 hours and seventh days, observed and recorded to apply position before administration and administration during the skin no erythema and edema, and observe the smear Parts of any pigmentation, bleeding, rough skin or thin skin etc., record the occurrence time and duration time. Through comparative observation, intact skin group before administration and dosing period, there were no erythema and edema, pigmentation, bleeding, rough skin or thin skin etc., there is no difference with the control group; the damaged skin group after administration of 1 to 5 days, each rabbit skin there are different degrees of erythema and edema, especially to skin injury after 24-48 hours is obvious, 2 days (48 hours) after 4 days gradually reduced, significantly subsided after 6 days, erythema and edema phenomenon subsided completely, not out of blood, pigmentation, rough skin or thin skin and so on. The bone spur powder has no irritation on the intact skin of rabbits. The bone spur powder has moderate irritation on the damaged skin of rabbits, but after 48 hours, the stimulation reaction subsided spontaneously, which is caused by the inflammatory reaction caused by skin injury, rather than the medication. The bone spur powder is safe for clinical use.

Comparison of Gadofluorine-M and Gd-DTPA for Non-Invasive Staging of Atherosclerotic Plaque Stability Using MRI

PubMed Central

Ronald, John A.; Chen, Yuanxin; Belisle, Andre J.-L.; Hamilton, Amanda M.; Rogers, Kem A.; Hegele, Robert A.; Misselwitz, Bernd; Rutt, Brian K.

2009-01-01

Background Inflammation and neovascularization play critical roles in the stability of atherosclerotic plaques. Whole-body quantitative assessment of these plaque features may improve patient risk-stratification for life-threatening thromboembolic events and direct appropriate intervention. Here we determined the utility of the MR contrast agent Gadofluorine-M (GdF) for staging plaque stability and compared this to the conventional agent Gd-DTPA. Methods and Results 5 control and 7 atherosclerotic rabbits were sequentially imaged following administration of Gd-DTPA (0.2 mmol/kg) and GdF (0.1 mmol/kg) using a T1-weighted pulse sequence on a 3T MRI scanner. Diseased aortic wall could be distinguished from normal wall based on wall-to-muscle contrast-to-noise values following GdF administration. RAM-11 (macrophages) and CD-31 (endothelial cells) immunostaining of MR-matched histological sections revealed that GdF accumulation was related to the degree of inflammation at the surface of plaques and the extent of core neovascularization. Importantly, an MR measure of GdF accumulation at both 1 and 24 hours post-injection, but not Gd-DTPA at peak enhancement, was shown to correlate with a quantitative histological morphology index related to these two plaque features. Conclusions GdF-enhanced MRI of atherosclerotic plaques allows non-invasive quantitative information about plaque composition to be acquired at multiple time points post-injection (within 1 and up to 24 hours post-injection). This dramatically widens the imaging window for assessing plaque stability that is currently attainable with clinically approved MR agents, therefore opening the possibility of whole-body (including coronary) detection of unstable plaques in the future and potentially improved mitigation of cataclysmic cardiovascular events. PMID:19808597

[Experimental study of tendon graft fixation in anterior cruciate ligament reconstruction with cortical press-fit bolt in rabbits].

PubMed

Qi, Wei; Li, Chun-bao; Wang, Jun-liang; Zhu, Juan-li; Liu, Yu-jie

2013-05-21

To explore the histological outcomes of tendon-bone healing in anterior cruciate ligament (ACL) reconstruction with cortical press-fit bolt (CPB). Twenty-four healthy female or male New Zealand White rabbits (2-3 months old) underwent bilateral ACL reconstruction with extensor digitorum longus tendon. A random method was used to decide one knee would receive the routine ACL reconstruction (control group) and another cortical press-fit bolt fixation (experimental group). After general anesthesia, extensor digitorum longus tendon was harvested and ACL reconstruction performed. All animals were sacrificed at 4, 8 and 12 weeks postoperation. Radiological and histological examinations were made at each timepoint. The specimens were stained with different methods to observe the pathological changes of tendon graft, bone tunnel and cortical press-fit bolt. More revascularization and massive new bone were found in tendon-bone junction of experimental group at 4, 8 and 12 weeks postoperation. The circum-graft new vessel proportion of the experimental and control groups were 0.48 ± 0.12 and 0.26 ± 0.05 respectively (P < 0.05). In the experimental group, more cartilage cells were present in tendon-bone junction at 12 weeks and the circum-graft new bone areas in two groups were 0.41 ± 0.11 and 0.21 ± 0.10 mm(2) respectively (P < 0.05). Cortical press-fit blot may improve tendon-bone healing after ACL reconstruction in rabbits. The application prospects of this procedure are promising.

Viability of ligaments after freezing: an experimental study in a rabbit model.

PubMed

Frank, C; Edwards, P; McDonald, D; Bodie, D; Sabiston, P

1988-01-01

Our purpose in this study was to assess ligament fibroblast viability after freezing by quantifying the subsequent ability of fibroblasts to synthesize collagen in vitro. Both medial collateral ligament (MCL) complexes from 40 adolescent rabbits were studied. Collagen production was determined by in vitro incubation of ligaments in 3H-proline (a collagen precursor) and subsequent analysis of 3H-hydroxyproline (a marker of newly synthesized collagen). Autoradiographs determined the distributions of ligament cell activity. All right MCL complexes served as fresh controls, providing a baseline of collagen production. Each left MCL was assigned to an experimental group and was either incubated fresh (10 animals); "killed" by drying, multiple freeze thawing, or cycloheximide (six animals); or slowly frozen at -70 degrees C without cryoprotection (24 animals). Collagen production of rapidly thawed ligaments was studied by proline incubation at 1 day, 9 days, or 6 weeks after freezing and was compared with that of contralateral fresh controls. Results demonstrate that some cells in the substance of these rabbit ligaments retained the ability to synthesize collagen in vitro after being frozen for up to 6 weeks. Mean collagen production of frozen ligaments was decreased, but tests of mean and median values as well as ratios were statistically similar to fresh contralateral ligaments in all animals. This postfreezing ligament cell survival and collagen production after -70 degrees C storage may have implications for ligament transplantation.

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

Ultrasound Tissue Characterization of Vulnerable Atherosclerotic Plaque

PubMed Central

Picano, Eugenio; Paterni, Marco

2015-01-01

A thrombotic occlusion of the vessel fed by ruptured coronary atherosclerotic plaque may result in unstable angina, myocardial infarction or death, whereas embolization from a plaque in carotid arteries may result in transient ischemic attack or stroke. The atherosclerotic plaque prone to such clinical events is termed high-risk or vulnerable plaque, and its identification in humans before it becomes symptomatic has been elusive to date. Ultrasonic tissue characterization of the atherosclerotic plaque is possible with different techniques—such as vascular, transesophageal, and intravascular ultrasound—on a variety of arterial segments, including carotid, aorta, and coronary districts. The image analysis can be based on visual, video-densitometric or radiofrequency methods and identifies three distinct textural patterns: hypo-echoic (corresponding to lipid- and hemorrhage-rich plaque), iso- or moderately hyper-echoic (fibrotic or fibro-fatty plaque), and markedly hyperechoic with shadowing (calcific plaque). Hypoechoic or dishomogeneous plaques, with spotty microcalcification and large plaque burden, with plaque neovascularization and surface irregularities by contrast-enhanced ultrasound, are more prone to clinical complications than hyperechoic, extensively calcified, homogeneous plaques with limited plaque burden, smooth luminal plaque surface and absence of neovascularization. Plaque ultrasound morphology is important, along with plaque geometry, in determining the atherosclerotic prognostic burden in the individual patient. New quantitative methods beyond backscatter (to include speed of sound, attenuation, strain, temperature, and high order statistics) are under development to evaluate vascular tissues. Although not yet ready for widespread clinical use, tissue characterization is listed by the American Society of Echocardiography roadmap to 2020 as one of the most promising fields of application in cardiovascular ultrasound imaging, offering unique

Powassan viral encephalitis: a review and experimental studies in the horse and rabbit.

PubMed

Little, P B; Thorsen, J; Moore, W; Weninger, N

1985-09-01

Powassan virus strain M794, a member of the Flavivirus genus known to infect man and animals in Canada, was inoculated intracerebrally into rabbits and horses. No clinical signs were observed in rabbits, but widespread encephalitis resulted, characterized by lymphoid perivascular cuffing, lymphocytic meningitis, and lymphocytic choroiditis. In horses, eight days after inoculation, prominent neurological signs occurred and lesions were those of non-suppurative encephalomyelitis, neuronal necrosis, and focal parenchymal necrosis. The virus could not be reisolated from the rabbit or horse brains. Pathologic features, useful in separating some of the common North American equine neurological diseases, are discussed.

Adverse Impact of Diet-Induced Hypercholesterolemia on Cardiovascular Tissue Homeostasis in a Rabbit Model: Time-Dependent Changes in Cardiac Parameters

PubMed Central

Kertész, Attila; Bombicz, Mariann; Priksz, Daniel; Balla, Jozsef; Balla, Gyorgy; Gesztelyi, Rudolf; Varga, Balazs; Haines, David D.; Tosaki, Arpad; Juhasz, Bela

2013-01-01

The present study evaluates a hypothesis that diet-related hypercholesterolemia increases oxidative stress-related burden to cardiovascular tissue, resulting in progressively increased mortality, along with deterioration of electrophysiological and enzymatic function in rabbit myocardium. New Zealand white rabbits were divided into four groups, defined as follows: GROUP I, cholesterol-free rabbit chow for 12 weeks; GROUP II, cholesterol-free chow, 40 weeks; GROUP III, chow supplemented with 2% cholesterol, 12 weeks; GROUP IV, chow supplemented with 2% cholesterol, 40 weeks. At the 12 and 40 weeks time points, animals in each of the aforementioned cohorts were subjected to echocardiographic measurements, followed by sacrifice. Significant deterioration in major outcome variables measured in the present study were observed only in animals maintained for 40 weeks on 2% cholesterol-supplemented chow, with much lesser adverse effects noted in animals fed high cholesterol diets for only 12 weeks. It was observed that rabbits receiving high cholesterol diets for 40 weeks exhibited significantly increased mortality, worsened ejection fraction and general deterioration of cardiac functions, along with increased atherosclerotic plaque formation and infarct size. Additionally, myocardium of GROUP IV animals was observed to contain lower levels of heme oxygenase-1 (HO-1) and cytochrome c oxidase III (COX III) protein relative to the controls. PMID:24048247

Does myxomatosis still regulate numbers of rabbits (Oryctolagus cuniculus Linnaeus, 1758) in the United Kingdom?

PubMed

Trout, R C; Ross, J; Fox, A P

1993-03-01

Myxomatosis now kills a much smaller proportion of rabbit populations than in the past, while remaining an important regulatory factor, as shown experimentally. On two separate occasions, experimental reduction of the prevalence of the disease (by reducing infestations of the main vector, the rabbit flea) led to significant increases in numbers of rabbits surviving the winter.

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

Adverse effects of the anabolic steroid, boldenone undecylenate, on reproductive functions of male rabbits.

PubMed

Oda, Samah S; El-Ashmawy, Ibrahim M

2012-06-01

This study was conducted to evaluate the adverse effects of the anabolic steroid, boldenone undecylenate (BOL) on reproductive functions of male rabbits. Thirty white New Zealand mature male rabbits were divided into three groups (10 rabbits each). Group A rabbits served as a control group. Group B rabbits received 4.4 mg/kg body weight (bwt) BOL 5% oily solution. Group C rabbits received 8.8 mg/kg bwt BOL. Rabbits were injected intramuscularly twice weekly for two months. BOL had no significant effect on the bwt and bwt gain. Testes and epididymis weights were decreased significantly in the BOL-treated groups. BOL caused significant reduction in serum testosterone level, seminal volume, sperm motility, and sperm count. No abnormalities were detected in the sperm morphology of the BOL-treated groups. Histopathological alterations in the testes and epididymis were marked in the group C rabbits. These results indicate that administration of BOL exerts a significant harmful effect on the reproductive functions of male rabbits. © 2012 The Authors. International Journal of Experimental Pathology © 2012 International Journal of Experimental Pathology.

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). Copyright © 2016 Elsevier Inc. All rights reserved.

Overexpression of TGF-ß1 in Macrophages Reduces and Stabilizes Atherosclerotic Plaques in ApoE-Deficient Mice

PubMed Central

Orning, Carolin; Crain, Jeanine; Küpper, Ines; Wiese, Elena; Protschka, Martina; Blessing, Manfred; Lackner, Karl J.; Torzewski, Michael

2012-01-01

Although macrophages represent the hallmark of both human and murine atherosclerotic lesions and have been shown to express TGF-ß1 (transforming growth factor β1) and its receptors, it has so far not been experimentally addressed whether the pleiotropic cytokine TGF-ß1 may influence atherogenesis by a macrophage specific mechanism. We developed transgenic mice with macrophage specific TGF-ß1 overexpression, crossed the transgenics to the atherosclerotic ApoE (apolipoprotein E) knock-out strain and quantitatively analyzed both atherosclerotic lesion development and composition of the resulting double mutants. Compared with control ApoE−/− mice, animals with macrophage specific TGF-ß1 overexpression developed significantly less atherosclerosis after 24 weeks on the WTD (Western type diet) as indicated by aortic plaque area en face (p<0.05). Reduced atherosclerotic lesion development was associated with significantly less macrophages (p<0.05 after both 8 and 24 weeks on the WTD), significantly more smooth muscle cells (SMCs; p<0.01 after 24 weeks on the WTD), significantly more collagen (p<0.01 and p<0.05 after 16 and 24 weeks on the WTD, respectively) without significant differences of inner aortic arch intima thickness or the number of total macrophages in the mice pointing to a plaque stabilizing effect of macrophage-specific TGF-ß1 overexpression. Our data shows that macrophage specific TGF-ß1 overexpression reduces and stabilizes atherosclerotic plaques in ApoE-deficient mice. PMID:22829904

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

PubMed

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

2015-01-09

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

Variant Rabbit Hemorrhagic Disease Virus in Young Rabbits, Spain

PubMed Central

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

2012-01-01

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. PMID:23171812

Progress in atherosclerotic plaque imaging

PubMed Central

Soloperto, Giulia; Casciaro, Sergio

2012-01-01

Cardiovascular diseases are the primary cause of mortality in the industrialized world, and arterial obstruction, triggered by rupture-prone atherosclerotic plaques, lead to myocardial infarction and cerebral stroke. Vulnerable plaques do not necessarily occur with flow-limiting stenosis, thus conventional luminographic assessment of the pathology fails to identify unstable lesions. In this review we discuss the currently available imaging modalities used to investigate morphological features and biological characteristics of the atherosclerotic plaque. The different imaging modalities such as ultrasound, magnetic resonance imaging, computed tomography, nuclear imaging and their intravascular applications are illustrated, highlighting their specific diagnostic potential. Clinically available and upcoming methodologies are also reviewed along with the related challenges in their clinical translation, concerning the specific invasiveness, accuracy and cost-effectiveness of these methods. PMID:22937215

Visualization of Monocytic Cells in Regressing Atherosclerotic Plaques by Intravital 2-Photon and Positron Emission Tomography-Based Imaging-Brief Report.

PubMed

Li, Wenjun; Luehmann, Hannah P; Hsiao, Hsi-Min; Tanaka, Satona; Higashikubo, Ryuji; Gauthier, Jason M; Sultan, Deborah; Lavine, Kory J; Brody, Steven L; Gelman, Andrew E; Gropler, Robert J; Liu, Yongjian; Kreisel, Daniel

2018-05-01

Aortic arch transplants have advanced our understanding of processes that contribute to progression and regression of atherosclerotic plaques. To characterize the dynamic behavior of monocytes and macrophages in atherosclerotic plaques over time, we developed a new model of cervical aortic arch transplantation in mice that is amenable to intravital imaging. Vascularized aortic arch grafts were transplanted heterotropically to the right carotid arteries of recipient mice using microsurgical suture techniques. To image immune cells in atherosclerotic lesions during regression, plaque-bearing aortic arch grafts from B6 ApoE-deficient donors were transplanted into syngeneic CX 3 CR1 GFP reporter mice. Grafts were evaluated histologically, and monocytic cells in atherosclerotic plaques in ApoE-deficient grafts were imaged intravitally by 2-photon microscopy in serial fashion. In complementary experiments, CCR2 + cells in plaques were serially imaged by positron emission tomography using specific molecular probes. Plaques in ApoE-deficient grafts underwent regression after transplantation into normolipidemic hosts. Intravital imaging revealed clusters of largely immotile CX 3 CR1 + monocytes/macrophages in regressing plaques that had been recruited from the periphery. We observed a progressive decrease in CX 3 CR1 + monocytic cells in regressing plaques and a decrease in CCR2 + positron emission tomography signal during 4 months. Cervical transplantation of atherosclerotic mouse aortic arches represents a novel experimental tool to investigate cellular mechanisms that contribute to the remodeling of atherosclerotic plaques. © 2018 American Heart Association, Inc.

Establishment of a New Zealand rabbit model of spinal tuberculosis.

PubMed

Geng, Guangqi; Wang, Qian; Shi, Jiandang; Yan, Junfa; Niu, Ningkui; Wang, Zili

2015-04-01

This was an experimental study. To investigate and evaluate the experimental method of establishing a New Zealand rabbit model of spinal tuberculosis. Establishing animal models of tuberculosis is critical to the experimental and clinical study of tuberculosis, especially spinal tuberculosis. However, the rapid spread of Mycobacterium tuberculosis and subsequent high mortality thwarted their effort. Since then, no animal models have been established of spinal tuberculosis. Forty-two New Zealand rabbits were randomly divided into experimental (n=20), control (n=20), and blank groups (n=2). Experimental animals were sensitized by complete Freund's adjuvant. A hole drilled under the upper endplate of the L4 vertebral body was filled with a gelfoam sponge infused with 0.1 mL H37Rv standard M. tuberculosis suspension (in controls, culture medium, and saline). Blank animals received no treatment. Survival 8 weeks after surgery was 89.5%, 94.7%, and 100% in experimental, control, and blank groups, respectively. The model was successfully established in all surviving experimental rabbits. In experimental animals, vertebral body destruction at 4 weeks was 50% by x-ray; 83.3% by computed tomography reconstruction and magnetic resonance imaging; at 8 weeks, 58.8% by x-ray and 100% by computed tomograph reconstruction and magnetic resonance imaging. At 8 weeks, experimental animals developed vertebral destruction, granulation, and necrosis and 17.6% had psoas abscess. Histopathology revealed numerous lymphocytes and epithelioid cells, trabecular bone fracture, and coagulative necrosis in the vertebrae of experimental animals; bacterium culture was 52.9% positive. Control and blank animals showed no such changes. A New Zealand rabbit of spinal tuberculosis model can be successfully established by drilling a hole in the upper endplate of the vertebral body, filling with gelfoam sponge infused with H37Rv standard M. tuberculosis suspension after sensitization by complete Freund

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

Recombinant rabbit leukemia inhibitory factor and rabbit embryonic fibroblasts support the derivation and maintenance of rabbit embryonic stem cells.

PubMed

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; Xu, Jie

2012-08-01

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.

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. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

CANCER BIOMARKERS IN HUMAN ATHEROSCLEROTIC LESIONS: DETECTION OF DNA ADDUCTS

EPA Science Inventory

Since somatic mutations are suspected to contribute to the pathogenesis not only of cancer but also of atherosclerotic plaques, we measured DNA adducts in the smooth muscle layer of atherosclerotic lesions in abnormal aorta specimens taken at surgery from seven patients. NA adduc...

The usefulness of optical analyses for detecting vulnerable plaques using rabbit models

NASA Astrophysics Data System (ADS)

Nakai, Kanji; Ishihara, Miya; Kawauchi, Satoko; Shiomi, Masashi; Kikuchi, Makoto; Kaji, Tatsumi

2011-03-01

Purpose: Carotid artery stenting (CAS) has become a widely used option for treatment of carotid stenosis. Although technical improvements have led to a decrease in complications related to CAS, distal embolism continues to be a problem. The purpose of this research was to investigate the usefulness of optical methods (Time-Resolved Laser- Induced Fluorescence Spectroscopy [TR-LIFS] and reflection spectroscopy [RS] as diagnostic tools for assessment of vulnerable atherosclerotic lesions, using rabbit models of vulnerable plaque. Materials & Methods: Male Japanese white rabbits were divided into a high cholesterol diet group and a normal diet group. In addition, we used a Watanabe heritable hyperlipidemic (WHHL) rabbit, because we confirmed the reliability of our animal model for this study. Experiment 1: TR-LIFS. Fluorescence was induced using the third harmonic wave of a Q switch Nd:YAG laser. The TR-LIFS was performed using a photonic multi-channel analyzer with ICCD (wavelength range, 200 - 860 nm). Experiment 2: RS. Refection spectra in the wavelength range of 900 to 1700 nm were acquired using a spectrometer. Results: In the TR-LIFS, the wavelength at the peak was longer by plaque formation. The TR-LIFS method revealed a difference in peak levels between a normal aorta and a lipid-rich aorta. The RS method showed increased absorption from 1450 to 1500 nm for lipid-rich plaques. We observed absorption around 1200 nm due to lipid only in the WHHL group. Conclusion: These methods using optical analysis might be useful for diagnosis of vulnerable plaques. Keywords: Carotid artery stenting, vulnerable plaque, Time-Resolved Laser-Induced Fluorescence

Are calcifying matrix vesicles in atherosclerotic lesions of cellular origin?

PubMed

Bobryshev, Yuri V; Killingsworth, Murray C; Huynh, Thuan G; Lord, Reginald S A; Grabs, Anthony J; Valenzuela, Stella M

2007-03-01

Over recent years, the role of matrix vesicles in the initial stages of arterial calcification has been recognized. Matrix calcifying vesicles have been isolated from atherosclerotic arteries and the biochemical composition of calcified vesicles has been studied. No studies have yet been carried out to examine the fine structure of matrix vesicles in order to visualize the features of the consequent stages of their calcification in arteries. In the present work, a high resolution ultrastructural analysis has been employed and the study revealed that matrix vesicles in human atherosclerotic lesions are heterogeneous with two main types which we classified. Type I calcified vesicles were presented by vesicles surrounded by two electron-dense layers and these vesicles were found to be resistant to the calcification process in atherosclerotic lesions in situ. Type II matrix vesicles were presented by vesicles surrounded by several electron-dense layers and these vesicles were found to represent calcifying vesicles in atherosclerotic lesions. To test the hypothesis that calcification of matrix vesicles surrounded by multilayer sheets may occur simply as a physicochemical process, independently from the cell regulation, we produced multilamellar liposomes and induced their calcification in vitro in a manner similar to that occurring in matrix vesicles in atherosclerotic lesions in situ.

Mix-breeding with HEV-infected swine induced inapparent HEV infection in SPF rabbits.

PubMed

Liu, Lin; Wang, Lin; Xia, Junke; Zhang, Yulin; Zeng, Hang; Liu, Peng; Zou, Qinghua; Wang, Ling; Zhuang, Hui

2016-04-01

Studies have shown that swine HEV (sHEV) and rabbit HEV (rHEV) can experimentally infect rabbits and swine, respectively. However, no published data have documented isolating sHEV strains from rabbits in natural environment so far. To clarify the possibility of natural cross-species transmission of sHEV to rabbits, the pigs with HEV infection were farmed along with SPF rabbits in the same enclosed space. Five of 10 rabbits had seroconversion for anti-HEV antibody from the third week after mix-breeding. However, HEV RNA remained undetectable in feces, serum, liver and bile of the ten rabbits; and no obvious elevation of ALT was observed. The results possibly suggested that sHEV might lead to an inapparent infection of SPF rabbits by fecal-oral route. © 2015 Wiley Periodicals, Inc.

Detection and quantification of angiogenesis in experimental valve disease with integrin-targeted nanoparticles and 19-fluorine MRI/MRS

PubMed Central

Waters, Emily A; Chen, Junjie; Allen, John S; Zhang, Huiying; Lanza, Gregory M; Wickline, Samuel A

2008-01-01

Background Angiogenesis is a critical early feature of atherosclerotic plaque development and may also feature prominently in the pathogenesis of aortic valve stenosis. It has been shown that MRI can detect and quantify specific molecules of interest expressed in cardiovascular disease and cancer by measuring the unique fluorine signature of appropriately targeted perfluorocarbon (PFC) nanoparticles. In this study, we demonstrated specific binding of ανβ3 integrin targeted nanoparticles to neovasculature in a rabbit model of aortic valve disease. We also showed that fluorine MRI could be used to detect and quantify the development of neovasculature in the excised aortic valve leaflets. Methods New Zealand White rabbits consumed a cholesterol diet for ~180 days and developed aortic valve thickening, inflammation, and angiogenesis mimicking early human aortic valve disease. Rabbits (n = 7) were treated with ανβ3 integrin targeted PFC nanoparticles or control untargeted PFC nanoparticles (n = 6). Competitive inhibition in vivo of nanoparticle binding (n = 4) was tested by pretreatment with targeted nonfluorinated nanoparticles followed 2 hours later by targeted PFC nanoparticles. 2 hours after treatment, aortic valves were excised and 19F MRS was performed at 11.7T. Integrated 19F spectral peaks were compared using a one-way ANOVA and Hsu's MCB (multiple comparisons with the best) post hoc t test. In 3 additional rabbits treated with ανβ3 integrin targeted PFC nanoparticles, 19F spectroscopy was performed on a 3.0T clinical scanner. The presence of angiogenesis was confirmed by immunohistochemistry. Results Valves of rabbits treated with targeted PFC nanoparticles had 220% more fluorine signal than valves of rabbits treated with untargeted PFC nanoparticles (p < 0.001). Pretreatment of rabbits with targeted oil-based nonsignaling nanoparticles reduced the fluorine signal by 42% due to competitive inhibition, to a level not significantly different from control

Rabbit collagenase. Immunological identity of the enzymes released from cells and tissues in normal and pathological conditions.

PubMed Central

Werb, Z; Reynolds, J J

1975-01-01

1. The immunological cross-reactivity between rabbit collagenases from a variety of normal and pathological sources was examined. The specific antibody raised against collagenase secreted from normal rabbit synovial fibroblasts gave reactions of complete identity with collagenases secreted from fibroblasts derived from rabbit skin, and from synovium from experimentally arthritic rabbits. 2. The rabbit fibroblast collagenase was immunologically identical with collagenases obtained from the organ culture medium of normal rabbit skin, synovium, ear fibrocartilage and subchondral bone. 3. Collagenases from the culture media of normal rabbit synovium and from hyperplastic synovium of rabbits made experimentally arthritic were identical. 4. The collagenase secreted from rabbit fibroblasts gave a reaction completely identical with that of a collagenase extracted directly from a rabbit carcinoma. 5. IgG (immunoglobulin G) from a specific antiserum to rabbit fibroblast collagenase was a potent inhibitor of the collagenases obtained from the culture media of the various rabbit cells and tissues. 6. Collagenases from human synovium and from mouse macrophages and bone were neither precipitated nor inhibited by antibodies to rabbit collagenase. 7. No immunoreactive material was found in lysates of rabbit polymorphonuclear leucocyte granules with the specific antisera to rabbit fibroblast collagenase. No evidence for inactive forms of rabbit collagenase in lysates of the rabbit synovial fibroblasts could be found, either by double immunodiffusion against the specific collagenase, or by displacement of active enzyme from inhibition by the IgG. Images PLATE 1 PMID:56176

The pathogenesis of cauliflower ear. An experimental study in rabbits.

PubMed

Ohlsén, L; Skoog, T; Sohn, S A

1975-01-01

Appreciating an imcomplete understanding of the pathogenesis of cauliflower ear, an experimental study was designed to demonstrate the pathophysiology of this deformity. The investigation was conducted in 2-month-old rabbits. In one ear a collection of blood was placed under the raised perichondrium which was then sutured back in place and the skin closed. In the other ear an equal amount of blood was deposited between the intact perichondrium and skin. In the first study new cartilage developed under the perichondrium, but in the ear in which the blood was left above the surface of the perichondrium-covered cartilage, complete resorption of the clot occurred. The cauliflower ear was thus shown to be generating cartilage, arising from a layer of raised perichondrium which was further stimulated by a sero-sanguinous medium. The subperichondrial hematoma was extensively invaded by chondroblasts within 2 weeks, and over a period of 4 weeks the new tissue gradually changed into more mature cartilage. It was a consistent finding that the separated perichondrium retracted, thus causing the original cartilage to rise and buckle over the hamatoma, similar to the picture observed in the human pathology.

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

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.

Quantifying progression and regression of thrombotic risk in experimental atherosclerosis.

PubMed

Palekar, Rohun U; Jallouk, Andrew P; Goette, Matthew J; Chen, Junjie; Myerson, Jacob W; Allen, John S; Akk, Antonina; Yang, Lihua; Tu, Yizheng; Miller, Mark J; Pham, Christine T N; Wickline, Samuel A; Pan, Hua

2015-07-01

Currently, there are no generally applicable noninvasive methods for defining the relationship between atherosclerotic vascular damage and risk of focal thrombosis. Herein, we demonstrate methods to delineate the progression and regression of vascular damage in response to an atherogenic diet by quantifying the in vivo accumulation of semipermeable 200-300 nm perfluorocarbon core nanoparticles (PFC-NP) in ApoE null mouse plaques with [(19)F] magnetic resonance spectroscopy (MRS). Permeability to PFC-NP remained minimal until 12 weeks on diet, then increased rapidly following 12 weeks, but regressed to baseline within 8 weeks after diet normalization. Markedly accelerated clotting (53.3% decrease in clotting time) was observed in carotid artery preparations of fat-fed mice subjected to photochemical injury as defined by the time to flow cessation. For all mice on and off diet, an inverse linear relationship was observed between the permeability to PFC-NP and accelerated thrombosis (P = 0.02). Translational feasibility for quantifying plaque permeability and vascular damage in vivo was demonstrated with clinical 3 T MRI of PFC-NP accumulating in plaques of atherosclerotic rabbits. These observations suggest that excessive permeability to PFC-NP may indicate prothrombotic risk in damaged atherosclerotic vasculature, which resolves within weeks after dietary therapy. © FASEB.

Mast cells in atherosclerotic cardiovascular disease - Activators and actions.

PubMed

Kovanen, Petri T; Bot, Ilze

2017-12-05

Mast cells are potent actors involved in inflammatory reactions in various tissues, including both in the intimal and the adventitial layers of atherosclerotic arteries. In the arterial intima, the site of atherogenesis, mast cells are activated to degranulate, and thereby triggered to release an abundance of preformed inflammatory mediators, notably histamine, heparin, neutral proteases and cytokines stored in their cytoplasmic secretory granules. Depending on the stimulus, mast cell activation may also launch prolonged synthesis and secretion of single bioactive molecules, such as cytokines and derivatives of arachidonic acid. The mast cell-derived mediators may impede the functions of different types of cells present in atherosclerotic lesions, and also compromise the structural and functional integrity of the intimal extracellular matrix. In the adventitial layer of atherosclerotic coronary arteries, mast cells locate next to peptidergic sensory nerve fibers, which, by releasing neuropeptides may activate mast cells to release vasoactive compounds capable of triggering local vasoconstriction. The concerted actions of arterial mast cells have the potential to contribute to the initiation and progression of atherosclerosis, and ultimately to destabilization and rupture of an advanced atherosclerotic plaque with ensuing atherothrombotic complications. Copyright © 2017 Elsevier B.V. All rights reserved.

Infectious Agents in Atherosclerotic Cardiovascular Diseases through Oxidative Stress.

PubMed

Di Pietro, Marisa; Filardo, Simone; Falasca, Francesca; Turriziani, Ombretta; Sessa, Rosa

2017-11-18

Accumulating evidence demonstrates that vascular oxidative stress is a critical feature of atherosclerotic process, potentially triggered by several infectious agents that are considered as risk co-factors for the atherosclerotic cardiovascular diseases (CVDs). C. pneumoniae has been shown to upregulate multiple enzymatic systems capable of producing reactive oxygen species (ROS) such as NADPH oxidase (NOX) and cyclooxygenase in vascular endothelial cells, NOX and cytochrome c oxidase in macrophages as well as nitric oxide synthase and lipoxygenase in platelets contributing to both early and late stages of atherosclerosis. P. gingivalis seems to be markedly involved in the atherosclerotic process as compared to A. actinomycetemcomitans contributing to LDL oxidation and foam cell formation. Particularly interesting is the evidence describing the NLRP3 inflammasome activation as a new molecular mechanism underlying P. gingivalis -induced oxidative stress and inflammation. Amongst viral agents, immunodeficiency virus-1 and hepatitis C virus seem to have a major role in promoting ROS production, contributing, hence, to the early stages of atherosclerosis including endothelial dysfunction and LDL oxidation. In conclusion, oxidative mechanisms activated by several infectious agents during the atherosclerotic process underlying CVDs are very complex and not well-known, remaining, thus, an attractive target for future research.

Effects of Uygur sand therapy on the mechanical properties of femurs in osteoarthritic rabbits.

PubMed

Maitirouzi, Julaiti; Yanna, Li; Abulizi, Adinaer; Aihemaitiniyazi, Aizezi; Kuerban, Shataer; Shaojun, Huang

2017-01-01

To investigate the effects of Uygur sand therapy on the mechanical properties of the femur bone of osteoarthritic rabbits. Sixteen rabbits were injected with papain in the right posterior femoral articular cavity on the first, fourth and seventh day to establish the osteoarthritis (OA) rabbit model. Animals were divided into the experimental group and control group (8 rabbits each). The experimental group was treated with sand therapy, and the control group received no sand therapy treatment. Computed tomography (CT) scanning was used to collect the data of the femur before modeling, after modeling and 14 and 28 days after sand treatment. A 3D model of the femur was generated with the MIMIC software the bone layer was divided according to the different gray values and the change of the bone volume was analyzed. The body mesh is divided, and the material properties are given, then the three-point bending simulation is performed in Ansys. Additionally, the three-point bending test was performed on all the rabbits' femur to obtain the deflection and maximum stress values. And the effects of the sand treatment on the volume and mechanical properties of the bone were analyzed. Finally, the simulation results are compared with the experimental results, and the effects of sand treatment on the volume and mechanical properties of the bone are analyzed. (1) there is a tendency in the control group to convert the hard bone into dense bone and soft bone, while in the experimental group, the soft bone is converted into dense bone and hard bone obviously; (2) the morphological parameters of the experimental group are lower than those of the control group, whereas the maximum load, maximum normal stress, maximum shear stress of the experimental group are higher than those of the control group. (3) The mechanical test of three-point bending test was carried out using the three dimensional finite element model of rabbit femur. The sand therapy has positive effects on the volume

Nonstimulated rabbit phonation model: Cricothyroid approximation.

PubMed

Novaleski, Carolyn K; Kojima, Tsuyoshi; Chang, Siyuan; Luo, Haoxiang; Valenzuela, Carla V; Rousseau, Bernard

2016-07-01

To describe a nonstimulated in vivo rabbit phonation model using an Isshiki type IV thyroplasty and uninterrupted humidified glottal airflow to produce sustained audible phonation. Prospective animal study. Six New Zealand white breeder rabbits underwent a surgical procedure involving an Isshiki type IV thyroplasty and continuous airflow delivered to the glottis. Phonatory parameters were examined using high-speed laryngeal imaging and acoustic and aerodynamic analysis. Following the procedure, airflow was discontinued, and sutures remained in place to maintain the phonatory glottal configuration for microimaging using a 9.4 Tesla imaging system. High-speed laryngeal imaging revealed sustained vocal fold oscillation throughout the experimental procedure. Analysis of acoustic signals revealed a mean vocal intensity of 61 dB and fundamental frequency of 590 Hz. Aerodynamic analysis revealed a mean airflow rate of 85.91 mL/s and subglottal pressure of 9 cm H2 O. Following the procedure, microimaging revealed that the in vivo phonatory glottal configuration was maintained, providing consistency between the experimental and postexperimental laryngeal geometry. The latter provides a significant milestone that is necessary for geometric reconstruction and to allow for validation of computational simulations against the in vivo rabbit preparation. We demonstrate a nonstimulated in vivo phonation preparation using an Isshiki type IV thyroplasty and continuous humidified glottal airflow in a rabbit animal model. This preparation elicits sustained vocal fold vibration and phonatory measures that are consistent with our laboratory's prior work using direct neuromuscular stimulation for evoked phonation. N/A. Laryngoscope, 126:1589-1594, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

[Effects of black and red rice on the formation of aortic plaques and blood lipids in rabbits].

PubMed

Chen, Q; Ling, W; Ma, J; Mei, J

2000-05-30

In order to observe the antiatherosclerotic effects of black and red rice and to find out their mechanism, 24 New Zealand male white rabbits (average body weight 1.91 kg) were divided randomly into three groups (white rice, black rice and red rice groups). The rabbits were fed a cholesterol-enriched diet (cholesterol 5 g/kg, lard 35 g/kg) containing 300 g/kg white, black and red rice powder respectively. The rabbits were sacrificed 10 weeks later. The aorta was dissected and stained in 0.5% oilred-isopropanol solution. The plaque area and total area of aorta were measured by an automatic image analyzer. Serum lipids were determined by an automatic analyzer. The results showed that the plaque area (% of total surface) in the black and red rice groups was significantly lower than that in the white rice group (P < 0.05). Serum TG, TC, LDL-C, ApoB and ApoAI/ApoB were not significantly different among the three groups (P > 0.05). However, the concentrations of HDL-C and ApoAI were significantly higher in the black and red rice groups than those in the white groups (P < 0.05). No significant difference was found between the black and red rice groups. It is concluded that black and red rice might be effective in reducing atherosclerotic plaques on the aorta of rabbits fed a cholesterol-enriched diet. The effectiveness of black and red rice against atherosclerosis might be related to the high level of serum HDL-C and ApoAI.

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

PubMed

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

2008-03-01

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

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

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

PubMed

Feng, Yuanbo; Bogaert, Jan; Oyen, Raymond; Ni, Yicheng

2014-10-01

To exploit the advantages of using rabbits for cardiac imaging research and to tackle the technical obstacles, efforts have been made under the framework of a doctoral research program. In this overview article, by cross-referencing the current literature, we summarize how we have developed a preclinical cardiac research platform based on modified models of reperfused myocardial infarction (MI) in rabbits; how the in vivo manifestations of cardiac imaging could be closely matched with those ex vivo macro- and microscopic findings; how these imaging outcomes could be quantitatively analyzed, validated and demonstrated; and how we could apply this cardiac imaging platform to provide possible solutions to certain lingering diagnostic and therapeutic problems in experimental cardiology. In particular, tissue components in acute cardiac ischemia have been stratified and characterized, post-infarct lipomatous metaplasia (LM) as a common but hardly illuminated clinical pathology has been identified in rabbit models, and a necrosis avid tracer as well as an anti-ischemic drug have been successfully assessed for their potential utilities in clinical cardiology. These outcomes may interest the researchers in the related fields and help strengthen translational research in cardiovascular diseases.

[Contents of calcium, phosphorus and aluminum in central nervous system, liver and kidney of rabbits with experimental atherosclerosis--scavenger effects of vinpocetine on the deposition of elements].

PubMed

Yasui, M; Yano, I; Ota, K; Oshima, A

1990-04-01

The aims in this study were designed to clarify the contents of calcium (Ca), phosphorus (P) and aluminum (Al) in central nervous system (CNS), liver and kidney of rabbits with atherosclerosis experimentally induced by cholesterol-rich diet, and investigate scavenger effect of 14-ethoxycarbonyl-(3 alpha, 16 alpha-ethyl)-14,15-eburnamenine (vinpocetine) on the deposition of these elements in CNS and soft tissues of experimental atherosclerosis. Sixteen male rabbits were divided into 4 groups. Each group was fed with standard diet (Group A), standard diet containing 1.5% cholesterol (Group B), standard diet containing 1.5% cholesterol plus oral administration of 3 mg/kg/day vinpocetine (Group C), and standard diet containing 1.5% cholesterol plus administration of 10 mg/kg/day vinpocetine (Group D). After 3 months' feeding, experimental atherosclerosis was produced with a modified method of Kritchevsky et al in rabbits of Groups B, C and D. Blood was collected by cardiocentesis under the anesthesia of ether and then rabbits sacrificed to remove CNS and other tissues. The blood was stood for 1 hour at room temperature and separated by centrifugation at 3000 rpm for 10 min to determine serum total cholesterol, phospholipids, HDL-cholesterol, peroxide lipid, NEFA and calcium levels. Ca, P and Al contents in the frontal lobe, pons, cerebellum, spinal cord, liver and kidney were determined by neutron activation analysis. Ca contents of CNS, liver and kidney in Group B significantly increased than those of Group A (p less than 0.01), and significantly decreased in Groups C and D compared with those of Group B (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Some further effects of prednisolone and triamcinolone hexacetonide on experimental arthritis in rabbits.

PubMed

Hunneyball, I M

1981-11-01

Prolonged treatment of rabbits with an established bilaterally symmetrical experimental arthritis with prednisolone (0.5 mg/kg day) reduced both the swelling and the histopathological changes in the arthritic joints whereas short-term treatment suppressed only the swelling. Such prolonged treatment also suppressed both the humoral and cell-mediated immune responses measured systemically in these animals and the cell-mediated immune responsiveness of the synovium determined by lymphokine production by cultured explants. The results suggested that the suppressive effect of the drug on the arthritis was related to the inhibition of cell-mediated immune responsiveness. Prednisolone treatment also had deleterious effect on cartilage proteoglycan metabolism determined both histologically and biochemically. Intra-articular administration of triamcinolone hexacetonide (three injections of 2 mg per joint at fortnightly intervals) also reduced the swelling and histopathological changes, although there was no effect on circulating antibody levels.

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

Emerging Technology Update Intravascular Photoacoustic Imaging of Vulnerable Atherosclerotic Plaque.

PubMed

Wu, Min; Fw van der Steen, Antonius; Regar, Evelyn; van Soest, Gijs

2016-10-01

The identification of vulnerable atherosclerotic plaques in the coronary arteries is emerging as an important tool for guiding atherosclerosis diagnosis and interventions. Assessment of plaque vulnerability requires knowledge of both the structure and composition of the plaque. Intravascular photoacoustic (IVPA) imaging is able to show the morphology and composition of atherosclerotic plaque. With imminent improvements in IVPA imaging, it is becoming possible to assess human coronary artery disease in vivo . Although some challenges remain, IVPA imaging is on its way to being a powerful tool for visualising coronary atherosclerotic features that have been specifically associated with plaque vulnerability and clinical syndromes, and thus such imaging might become valuable for clinical risk assessment in the catheterisation laboratory.

Anti-atherosclerotic therapy based on botanicals.

PubMed

Orekhov, Alexander N; Sobenin, Igor A; Korneev, Nikolay V; Kirichenko, Tatyana V; Myasoedova, Veronika A; Melnichenko, Alexandra A; Balcells, Mercedes; Edelman, Elazer R; Bobryshev, Yuri V

2013-04-01

Natural products including botanicals for both therapy of clinical manifestations of atherosclerosis and reduction of atherosclerosis risk factors are topics of recent patents. Only a few recent patents are relevant to the direct antiatherosclerotic therapy leading to regression of atherosclerotic lesions. Earlier, using a cellular model we have developed and patented several anti-atherosclerotic drugs. The AMAR (Atherosclerosis Monitoring and Atherogenicity Reduction) study was designed to estimate the effect of two-year treatment with time-released garlic-based drug Allicor on the progression of carotid atherosclerosis in 196 asymptomatic men aged 40-74 in double-blinded placebo-controlled randomized clinical study. The primary outcome was the rate of atherosclerosis progression, measured by high-resolution B-mode ultrasonography as the increase in carotid intima-media thickness (IMT) of the far wall of common carotid arteries. The mean rate of IMT changes in Allicor-treated group (-0.022±0.007 mm per year) was significantly different (P = 0.002) from the placebo group in which there was a moderate progression of 0.015±0.008 mm at the overall mean baseline IMT of 0.931±0.009 mm. A significant correlation was found between the changes in blood serum atherogenicity (the ability of serum to induce cholesterol accumulation in cultured cells) during the study and the changes in intima-media thickness of common carotid arteries (r = 0.144, P = 0.045). Thus, the results of AMAR study demonstrate that long-term treatment with Allicor has a direct anti-atherosclerotic effect on carotid atherosclerosis and this effect is likely to be due to serum atherogenicity inhibition. The beneficial effects of other botanicals including Inflaminat (calendula, elder and violet), phytoestrogen- rich Karinat (garlic powder, extract of grape seeds, green tea leafs, hop cones, β-carotene, α-tocopherol and ascorbic acid) on atherosclerosis have also been revealed in clinical studies

Growth performance and meat quality of rabbits under different feeding regimes.

PubMed

Khan, Kamran; Khan, Sarzamin; Khan, Rajwali; Sultan, Asad; Khan, Nazir Ahmad; Ahmad, Naseer

2016-12-01

This study evaluated the growth, carcass characteristics and meat quality of indigenous rabbits in northern Pakistan. Weaned rabbits (age 35 days, weight 323 g) of four distinct phenotypes (white, black and white, brown and black) were fed four experimental diets: alfalfa hay (AH), berseem fodder (BF), BF supplemented with low-level concentrate (50 %; LLC) and high-level concentrate (75 %; HLC). Each experimental diet was fed to 48 rabbits, 12 of each phenotype, in a randomized complete block design. The duration of the experiment was 55 days, including 1 week of adaptation. Rabbits fed the BF and AH diets had poor body weight gain (P < 0.05) compared to rabbits fed the LLC and HLC diets. Feed conversion efficiency was best in the LLC (4.47) and HLC (4.58) groups. Average carcass yield (743 g) and carcass dressing percentage (56.2) were higher (P < 0.05) in LLC. Growth rate was not improved significantly by feeding HLC. Fat deposition in animals was higher (P < 0.05) in the groups supplemented with concentrate. Cost per kilogram of rabbit meat was lowest (P < 0.05) for BF, followed by AH, LLC and HLC. Brown phenotypes had the best (P < 0.05) feed conversion efficiency, body weight gain, carcass yield and carcass dressing. It was concluded that local rabbits do not necessarily need high levels of concentrates but can be well fattened with low-level concentrates along with forages.

Infectious Agents in Atherosclerotic Cardiovascular Diseases through Oxidative Stress

PubMed Central

Di Pietro, Marisa; Filardo, Simone; Falasca, Francesca; Turriziani, Ombretta; Sessa, Rosa

2017-01-01

Accumulating evidence demonstrates that vascular oxidative stress is a critical feature of atherosclerotic process, potentially triggered by several infectious agents that are considered as risk co-factors for the atherosclerotic cardiovascular diseases (CVDs). C. pneumoniae has been shown to upregulate multiple enzymatic systems capable of producing reactive oxygen species (ROS) such as NADPH oxidase (NOX) and cyclooxygenase in vascular endothelial cells, NOX and cytochrome c oxidase in macrophages as well as nitric oxide synthase and lipoxygenase in platelets contributing to both early and late stages of atherosclerosis. P. gingivalis seems to be markedly involved in the atherosclerotic process as compared to A. actinomycetemcomitans contributing to LDL oxidation and foam cell formation. Particularly interesting is the evidence describing the NLRP3 inflammasome activation as a new molecular mechanism underlying P. gingivalis-induced oxidative stress and inflammation. Amongst viral agents, immunodeficiency virus-1 and hepatitis C virus seem to have a major role in promoting ROS production, contributing, hence, to the early stages of atherosclerosis including endothelial dysfunction and LDL oxidation. In conclusion, oxidative mechanisms activated by several infectious agents during the atherosclerotic process underlying CVDs are very complex and not well-known, remaining, thus, an attractive target for future research. PMID:29156574

THE COURSE OF EXPERIMENTAL HEMOTHORAX IN RADIATION SICKNESS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, C.C.

1957-05-01

Experimental hemothorax induced by injecting 10 to 12 ml of autogenous blood into the pleural cavity of healthy rabbits was borne well without any marked general reaction. Rabbits irradiated with 600 r were more affected by experimental hemothorax. Instead of absorption, exudation accumulated in the pleural cavity. In rabbits irradiated with 600 r, experimental hemothorax markediy shortened the latent period of radiation sickness and hastened its climax. (C.H.)

Loganic acid and anthocyanins from cornelian cherry (Cornus mas L.) fruits modulate diet-induced atherosclerosis and redox status in rabbits.

PubMed

Sozański, Tomasz; Kucharska, Alicja Z; Dzimira, Stanisław; Magdalan, Jan; Szumny, Dorota; Matuszewska, Agnieszka; Nowak, Beata; Piórecki, Narcyz; Szeląg, Adam; Trocha, Małgorzata

2018-04-25

Cornelian cherry (Cornus mas L.) is a plant growing in southeast Europe, in the past used in folk medicine. There are many previous publications showing the preventive effects of (poly)phenolic compounds, especially anthocyanins, on cardiovascular diseases, but there is a lack of studies comparing the effects of (poly)phenolics and other constituents of fruits. We have attempted to determine if iridoids and anthocyanins from cornelian cherry fruits may affect the formation of atherosclerotic plaques in the aorta as well as lipid peroxidation and oxidative stress in the livers of cholesterol-fed rabbits. Fractions of iridoids and anthocyanins were analyzed using the high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS) methods. Loganic acid (20 mg/kg b.w.) and a mixture of anthocyanins (10 mg/kg b.w.) were administered orally for 60 days to rabbits fed with 1% cholesterol. Histopathological samples of the aortas and the livers were stained with hematoxylin and eosin. Lipid peroxidation (malondialdehyde - MDA) and redox status (glutathione - GSH, glutathione peroxidase - Gpx and superoxide dismutase - SOD) were analyzed using spectrophotometrical methods. Both loganic acid (an iridoid) and a mixture of anthocyanins diminished the formation of atherosclerotic plaques in the aorta. Both substances also diminished lipid peroxidation, measured as a decrease of MDA, and attenuated oxidative stress, measured as an increase of GSH in the livers depleted by cholesterol feeding. Unexpectedly, cholesterol feeding decreased the Gpx activity in the liver, which was reversed by both investigated substances. We have shown that both iridoids and anthocyanins help prevent fed-induced atherosclerosis, and the consumption of fruits rich in these substances may elicit beneficial effects on the cardiovascular system.

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

PubMed

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

2017-07-01

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

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.

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.

Globular domain of adiponectin: promising target molecule for detection of atherosclerotic lesions

PubMed Central

Almer, Gunter; Saba-Lepek, Matthias; Haj-Yahya, Samih; Rohde, Eva; Strunk, Dirk; Fröhlich, Eleonore; Prassl, Ruth; Mangge, Harald

2011-01-01

Background: Adiponectin, an adipocyte-specific plasma protein, has been shown to accumulate in injured endothelial cells during development of atherosclerotic lesions. In this study, we investigated the potential of different adiponectin subfractions with special emphasis on globular adiponectin (gAd) to recognize and visualize atherosclerotic lesions. Methods: Recombinant mouse gAd and subfractions of full-length adiponectin (ie, trimeric, hexameric, and oligomeric forms) were fluorescence-labeled. Aortas of wild-type and apoprotein E-deficient mice fed a high cholesterol diet were dissected and incubated with the labeled biomarkers. Imaging was performed using confocal laser scanning microscopy. Results: Confocal laser scanning microscopic images showed that gAd binds more strongly to atherosclerotic plaques than full-length adiponectin subfractions. Further, we showed that gAd accumulates preferentially in endothelial cells and the fibrous cap area of plaques. Here we demonstrate for the first time that gAd recognizes atherosclerotic plaques on aortic sections of apoprotein E-deficient mice. Conclusion: These results suggest that gAd, in addition to its physiological properties, is also suitable as a target molecule for prospective diagnostic strategies in imaging atherosclerotic lesions. PMID:22022204

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.

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.

Linkages between oral commensal bacteria and atherosclerotic plaques in coronary artery disease patients.

PubMed

Chhibber-Goel, Jyoti; Singhal, Varsha; Bhowmik, Debaleena; Vivek, Rahul; Parakh, Neeraj; Bhargava, Balram; Sharma, Amit

2016-01-01

Coronary artery disease is an inflammatory disorder characterized by narrowing of coronary arteries due to atherosclerotic plaque formation. To date, the accumulated epidemiological evidence supports an association between oral bacterial diseases and coronary artery disease, but has failed to prove a causal link between the two. Due to the recent surge in microbial identification and analyses techniques, a number of bacteria have been independently found in atherosclerotic plaque samples from coronary artery disease patients. In this study, we present meta-analysis from published studies that have independently investigated the presence of bacteria within atherosclerotic plaque samples in coronary artery disease patients. Data were collated from 63 studies covering 1791 patients spread over a decade. Our analysis confirms the presence of 23 oral commensal bacteria, either individually or in co-existence, within atherosclerotic plaques in patients undergoing carotid endarterectomy, catheter-based atherectomy, or similar procedures. Of these 23 bacteria, 5 ( Campylobacter rectus , Porphyromonas gingivalis , Porphyromonas endodontalis , Prevotella intermedia , Prevotella nigrescens ) are unique to coronary plaques, while the other 18 are additionally present in non-cardiac organs, and associate with over 30 non-cardiac disorders. We have cataloged the wide spectrum of proteins secreted by above atherosclerotic plaque-associated bacteria, and discuss their possible roles during microbial migration via the bloodstream. We also highlight the prevalence of specific poly-microbial communities within atherosclerotic plaques. This work provides a resource whose immediate implication is the necessity to systematically catalog landscapes of atherosclerotic plaque-associated oral commensal bacteria in human patient populations.

64Cu-Labeled Divalent Cystine Knot Peptide for Imaging Carotid Atherosclerotic Plaques.

PubMed

Jiang, Lei; Tu, Yingfeng; Kimura, Richard H; Habte, Frezghi; Chen, Hao; Cheng, Kai; Shi, Hongcheng; Gambhir, Sanjiv Sam; Cheng, Zhen

2015-06-01

The rupture of vulnerable atherosclerotic plaques that lead to stroke and myocardial infarction may be induced by macrophage infiltration and augmented by the expression of integrin αvβ3. Indeed, atherosclerotic angiogenesis may be a promising marker of inflammation. In this study, an engineered integrin αvβ3-targeting PET probe, (64)Cu-NOTA-3-4A, derived from a divalent knottin miniprotein was evaluated in a mouse model for carotid atherosclerotic plaques. Atherosclerotic plaques in BALB/C mice, maintained on a high-fat diet, were induced with streptozotocin injection and carotid artery ligation and verified by MR imaging. Knottin 3-4A was synthesized by solid-phase peptide synthesis chemistry and coupled to 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) before radiolabeling with (64)Cu. PET probe stability in mouse serum was evaluated. Mice with carotid atherosclerotic plaques were injected via the tail vein with (64)Cu-NOTA-3-4A or (18)F-FDG, followed by small-animal PET/CT imaging at different time points. Receptor targeting specificity of the probe was verified by coinjection of c(RGDyK) administered in molar excess. Subsequently, carotid artery dissection and immunofluorescence staining were performed to evaluate target expression. (64)Cu-NOTA-3-4A was synthesized in high radiochemical purity and yield and demonstrated molecular stability in both phosphate-buffered saline and mouse serum at 4 h. Small-animal PET/CT showed that (64)Cu-NOTA-3-4A accumulated at significantly higher levels in the neovasculature of carotid atherosclerotic plaques (7.41 ± 1.44 vs. 0.67 ± 0.23 percentage injected dose/gram, P < 0.05) than healthy or normal vessels at 1 h after injection. (18)F-FDG also accumulated in atherosclerotic lesions at 0.5 and 1 h after injection but at lower plaque-to-normal tissue ratios than (64)Cu-NOTA-3-4A. For example, plaque-to-normal carotid artery ratios for (18)F-FDG and (64)Cu-NOTA-3-4A at 1 h after injection were 3.75 and 14.71 (P < 0

Reducing variation in a rabbit vaccine safety study with particular emphasis on housing conditions and handling.

PubMed

Verwer, Cynthia M; van der Ark, Arno; van Amerongen, Geert; van den Bos, Ruud; Hendriksen, Coenraad F M

2009-04-01

This paper describes the results of a study of the effects of modified housing conditions, conditioning and habituation on humans using a rabbit model for monitoring whole-cell pertussis vaccine (pWCV)-induced adverse effects. The study has been performed with reference to previous vaccine safety studies of pWCV in rabbits in which results were difficult to interpret due to the large variation in experimental outcome, especially in the key parameter deep-body temperature (T(b)). Certain stressful laboratory conditions, as well as procedures involving humans, e.g. blood sampling, inoculation and cage-cleaning, were hypothesized to cause this large variation. The results of this study show that under modified housing conditions rabbits have normal circadian body temperatures. This allowed discrimination of pWCV-induced adverse effects in which handled rabbits tended to show a dose-related increase in temperature after inoculation with little variance, whereas non-handled rabbits did not. Effects of experimental and routine procedures on body temperature were significantly reduced under modified conditions and were within the normal T(b) range. Handled animals reacted less strongly and with less variance to experimental procedures, such as blood sampling, injection and cage-cleaning, than non-handled rabbits. Overall, handling had a positive effect on the behaviour of the animals. Data show that the housing modifications have provided a more robust model for monitoring pWCV adverse effects. Furthermore, conditioning and habituation of rabbits to humans reduce the variation in experimental outcome, which might allow for a reduction in the number of animals used. In addition, this also reduces distress and thus contributes to refining this animal model.

Haloperidol inhibits the development of atherosclerotic lesions in LDL receptor knockout mice

PubMed Central

van der Sluis, Ronald J; Nahon, Joya E; Reuwer, Anne Q; Van Eck, Miranda; Hoekstra, Menno

2015-01-01

Background and Purpose Antipsychotic drugs have been shown to modulate the expression of ATP-binding cassette transporter A1 (ABCA1), a key factor in the anti-atherogenic reverse cholesterol transport process, in vitro. Here we evaluated the potential of the typical antipsychotic drug haloperidol to modulate the cholesterol efflux function of macrophages in vitro and their susceptibility to atherosclerosis in vivo. Experimental Approach Thioglycollate-elicited peritoneal macrophages were used for in vitro studies. Hyperlipidaemic low-density lipoprotein (LDL) receptor knockout mice were implanted with a haloperidol-containing pellet and subsequently fed a Western-type diet for 5 weeks to induce the development of atherosclerotic lesions in vivo. Key Results Haloperidol induced a 54% decrease in the mRNA expression of ABCA1 in peritoneal macrophages. This coincided with a 30% decrease in the capacity of macrophages to efflux cholesterol to apolipoprotein A1. Haloperidol treatment stimulated the expression of ABCA1 (+51%) and other genes involved in reverse cholesterol transport, that is, CYP7A1 (+98%) in livers of LDL receptor knockout mice. No change in splenic ABCA1 expression was noted. However, the average size of the atherosclerotic size was significantly smaller (−31%) in the context of a mildly more atherogenic metabolic phenotype upon haloperidol treatment. More importantly, haloperidol markedly lowered MCP-1 expression (−70%) and secretion (−28%) by peritoneal macrophages. Conclusions and Implications Haloperidol treatment lowered the susceptibility of hyperlipidaemic LDL receptor knockout mice to develop atherosclerotic lesions. Our findings suggest that the beneficial effect of haloperidol on atherosclerosis susceptibility can be attributed to its ability to inhibit macrophage chemotaxis. PMID:25572138

The thrombin inhibitor argatroban does not influence the endothelium-dependent relaxant and contractile responses of isolated rabbit carotid arteries.

PubMed

Schrödter, Hans-Martin; Glusa, Erika

2003-06-01

Atherosclerotic endothelial dysfunctions are associated with a reduced NO production, which is probably due to impaired NO synthase (eNOS) activity or a deficiency of the substrate L-arginine. In the present studies, the influence of argatroban on isolated rabbit carotid arteries was investigated to determine whether the arginine derivative argatroban can improve the endothelium-dependent relaxation. Rings from rabbit carotid arteries were placed in 10 ml organ baths for isometric tension recording. Endothelial integrity was assessed by the acetylcholine-induced relaxation of PGF2alpha-precontracted rings; after mechanical removal of the endothelium the relaxation was abolished. Preincubation of the vessels in vitro with L-NAME, an inhibitor of the eNOS, diminished significantly the acetylcholine-induced relaxation by more than 50%. After i.v. application of L-NAME (100 mg/kg) in rabbits, relaxation in response to acetylcholine was significantly reduced compared to the control when the vessels were studied ex vivo in an organ bath. The contractile effects of phenylephrine and 5-HT were slightly enhanced. Argatroban is a selective, potent, synthetic thrombin inhibitor; after i.v. application at doses of 0.5 and 1.0 mg/kg, a significant prolongation of the plasma coagulation time (measured as thrombin time and a PTT) of up to 60 min was found in rabbits. In vitro argatroban did not affect the acetylcholine-induced relaxation or the contractile response to phenylephrine and 5-HT. After i.v. application, the ex vivo experiments in the organ bath showed that after 30 min the relaxant responses of the carotid arteries to acetylcholine and the contractile effects of phenylephrine and 5-HT were not influenced by pretreatment with argatroban. The present studies suggest that argatroban has no vascular effects in vitro and ex vivo in normal rabbits.

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

Bilirubin and atherosclerotic diseases.

PubMed

Vítek, L

2017-04-05

Bilirubin is the final product of heme catabolism in the systemic circulation. For decades, increased serum/plasma bilirubin levels were considered an ominous sign of an underlying liver disease. However, data from recent years convincingly suggest that mildly elevated bilirubin concentrations are associated with protection against various oxidative stress-mediated diseases, atherosclerotic conditions being the most clinically relevant. Although scarce data on beneficial effects of bilirubin had been published also in the past, it took until 1994 when the first clinical study demonstrated an increased risk of coronary heart disease in subjects with low serum bilirubin levels, and bilirubin was found to be a risk factor for atherosclerotic diseases independent of standard risk factors. Consistent with these results, we proved in our own studies, that subjects with mild elevation of serum levels of unconjugated bilirubin (benign hyperbilirubinemia, Gilbert syndrome) have much lower prevalence/incidence of coronary heart as well as peripheral vascular disease. We have also demonstrated that this association is even more general, with serum bilirubin being a biomarker of numerous other diseases, often associated with increased risk of atherosclerosis. In addition, very recent data have demonstrated biological pathways modulated by bilirubin, which are responsible for observed strong clinical associations.

Temporal shifts in clinical presentation and underlying mechanisms of atherosclerotic disease.

PubMed

Pasterkamp, Gerard; den Ruijter, Hester M; Libby, Peter

2017-01-01

The concept of the 'vulnerable plaque' originated from pathological observations in patients who died from acute coronary syndrome. This recognition spawned a generation of research that led to greater understanding of how complicated atherosclerotic plaques form and precipitate thrombotic events. In current practice, an increasing number of patients who survive their first event present with non-ST-segment elevation myocardial infarction (NSTEMI) rather than myocardial infarction (MI) with ST-segment elevation (STEMI). The culprit lesions that provide the pathological substrate for NSTEMI can vary considerably from the so-called 'vulnerable plaque'. The shift in clinical presentation of MI and stroke corresponds temporally to a progressive change in the characteristics of human plaques away from the supposed characteristics of vulnerability. These alterations in the structure and function of human atherosclerotic lesions might mirror the modifications that are produced in experimental plaques by lipid lowering, inspired by the vulnerable plaque construct. The shift in the clinical presentations of the acute coronary syndromes mandates a critical reassessment of the underlying mechanisms, proposed risk scores, the results and interpretation of preclinical experiments, as well as recognition of the limitations of the use of population data and samples collected before the application of current preventive interventions.

From rabbit antibody repertoires to rabbit monoclonal antibodies.

PubMed

Weber, Justus; Peng, Haiyong; Rader, Christoph

2017-03-24

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.

FELASA recommendations for the health monitoring of mouse, rat, hamster, guinea pig and rabbit colonies in breeding and experimental units.

PubMed

Mähler Convenor, M; Berard, M; Feinstein, R; Gallagher, A; Illgen-Wilcke, B; Pritchett-Corning, K; Raspa, M

2014-07-01

The microbiological quality of experimental animals can critically influence animal welfare and the validity and reproducibility of research data. It is therefore important for breeding and experimental facilities to establish a laboratory animal health monitoring (HM) programme as an integrated part of any quality assurance system. FELASA has published recommendations for the HM of rodent and rabbit colonies in breeding and experimental units (Nicklas et al. Laboratory Animals, 2002), with the intention of harmonizing HM programmes. As stated in the preamble, these recommendations need to be adapted periodically to meet current developments in laboratory animal medicine. Accordingly, previous recommendations have been revised and shall be replaced by the present recommendations. These recommendations are aimed at all breeders and users of laboratory mice, rats, Syrian hamsters, guinea pigs and rabbits as well as diagnostic laboratories. They describe essential aspects of HM, such as the choice of agents, selection of animals and tissues for testing, frequency of sampling, commonly used test methods, interpretation of results and HM reporting. Compared with previous recommendations, more emphasis is put on the role of a person with sufficient understanding of the principles of HM, opportunistic agents, the use of sentinel animals (particularly under conditions of cage-level containment) and the interpretation and reporting of HM results. Relevant agents, testing frequencies and literature references are updated. Supplementary information on specific agents and the number of animals to be monitored and an example of a HM programme description is provided in the appendices. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Subclavian steal syndrome decreases neurogenesis in the cerebellar cortex and affects cognitive function in rabbits.

PubMed

Fu, Xiao-Yang; Zhang, Zhi-Dong; Liang, Kai; Shi, Shuai-Tao; Wang, Guo-Quan; Zhang, Ke-Wei; Li, Kun; Li, Wei-Xiao; Li, Tian-Xiao; Zhai, Shui-Ting

2015-10-01

Subclavian steal syndrome (SSS) is a condition characterized by a steno-occlusive impairment of the proximal subclavian artery. The majority of patients with SSS are asymptomatic, while symptomatic patients present with neurological symptoms. SSS is a risk factor for cerebral ischemia, which reacts badly upon cognitive function; however, it remains unknown whether SSS is able to cause progressive cognitive impairment. In the present study, the potential effects of SSS on cognitive function were investigated using atherosclerotic rabbits as a model of SSS. A total of 48 male New Zealand rabbits were divided into the control, sham and SSS groups. The results of eyeblink experiments indicated no significant differences among the three groups; however, SSS did appear to exert a negative impact on neurogenesis in the cerebellar cortex. In order to further clarify the mechanisms underlying this SSS-mediated reduction in cell proliferation, the energy metabolism, immune function and oxidative stress statuses were evaluated by determining the levels of adenosine triphosphate (ATP), adenosine, interleukin (IL)-1β, IL-6, malondialdehyde, 8-hydroxy-2'-deoxyguanosine, CuZn-superoxide dismutase and catalase. The results showed that the levels of extracellular ATP in the cerebellar cortex had decreased, while levels of adenosine had also decreased. These findings suggest that SSS is able to inhibit neurogenesis in the cerebellar cortex by decreasing the extracellular ATP levels. Furthermore, these changes may result in an impairment of the cognition of the rabbits. The early diagnosis and treatment of SSS may, therefore, prevent or mitigate cognitive impairment in the future.

Pharmacokinetics and therapeutic efficacy of gentamicin in an experimental pleural empyema rabbit model.

PubMed Central

Shohet, I; Yellin, A; Meyerovitch, J; Rubinstein, E

1987-01-01

The pharmacokinetics and therapeutic efficacy of gentamicin were investigated in an experimental pleural empyema rabbit model. Pleural effusion was induced by the intrapleural administration of turpentine, and empyema was induced by direct inoculation of the effusion with Klebsiella pneumoniae. Pleural empyema compared with effusion was characterized by lower pH, oxygen tension (PaO2), and glucose levels and higher leukocyte count, lactic acid concentration, and PaCO2. After a single administration, gentamicin was first detectable in the pleural fluid at 60 min, whereas peak levels in empyema were observed at 180 min. Gentamicin persisted in the empyema longer than in blood. Animals treated with gentamicin only had 60% bacterial cure on day 7; those treated with gentamicin in an oxygen chamber had 100% cure on day 5 (P = 0.004). Low oxygen tension diminished the antibacterial efficacy of gentamicin in this model. An increase in oxygen tension improved the therapeutic results without alteration of the pharmacokinetics of gentamicin. PMID:3116920

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

Detection of High-Risk Atherosclerotic Plaque

PubMed Central

Fleg, Jerome L.; Stone, Gregg W.; Fayad, Zahi A.; Granada, Juan F.; Hatsukami, Thomas S.; Kolodgie, Frank D.; Ohayon, Jacques; Pettigrew, Roderic; Sabatine, Marc S.; Tearney, Guillermo; Waxman, Sergio; Domanski, Michael J.; Srinivas, Pothur R.; Narula, Jagat

2013-01-01

The leading cause of major morbidity and mortality in most countries around the world is atherosclerotic cardiovascular disease, most commonly caused by thrombotic occlusion of a high-risk coronary plaque resulting in myocardial infarction or cardiac death, or embolization from a high-risk carotid plaque resulting in stroke. The lesions prone to result in such clinical events are termed vulnerable or high-risk plaques, and their identification may lead to the development of pharmacological and mechanical intervention strategies to prevent such events. Autopsy studies from patients dying of acute myocardial infarction or sudden death have shown that such events typically arise from specific types of atherosclerotic plaques, most commonly the thin-cap fibroatheroma. However, the search in human beings for vulnerable plaques before their becoming symptomatic has been elusive. Recently, the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study demonstrated that coronary plaques that are likely to cause future cardiac events, regardless of angiographic severity, are characterized by large plaque burden and small lumen area and/or are thin-cap fibroatheromas verified by radiofrequency intravascular ultrasound imaging. This study opened the door to identifying additional invasive and noninvasive imaging modalities that may improve detection of high-risk atherosclerotic lesions and patients. Beyond classic risk factors, novel biomarkers and genetic profiling may identify those patients in whom noninvasive imaging for vulnerable plaque screening, followed by invasive imaging for risk confirmation is warranted, and in whom future pharmacological and/or device-based focal or regional therapies may be applied to improve long-term prognosis. PMID:22974808

[The rabbit experimental study for toxicokinetics of chlorpyrifos impacted by hemoperfusion].

PubMed

Guo, Xiang; Chen, Xiao; Zhang, Hongshun; Long, Xin; He, Qian; Sun, Chengye; Huang, Xianqing; He, Jian

2015-11-01

To investigate toxicokinetic parameters impacted by hemoperfusion after oral chlorpyrifos exposure, to investigate the adsorption effect of hemoperhusion for chlorpyrifos poisoning. 12 rabbits were divided into two groups after oral exposure with chlorpyrifos 300 mg/kg body weight. Control group: without hemoperfusion; hemoperfusion group: hemoperfusion starts 0.5 h after chlorpyrifos exposure and lasts for 2h. Blood samples were collected at different times, concentrations of chlorpyrifos were tested by GC, then, toxicokinetic parameterswere calculated and analysis by DAS3.0. In hemoperfusion group, peak time was (7.19±3.74) h, peak concentrations was (1.37±0.56) mg/L, clearance rate was (13.93±10.27) L/h/kg, apparent volume of distribution was (418.18±147.15) L/kg The difference of these parameter were statistically significant compared with control group (P<0.05). Hmoperfusion will decrease the inner exposure and load dose of rabbits with chlorpyrifos poisoning.

A rabbit model of non-typhoidal Salmonella bacteremia.

PubMed

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

2014-09-01

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

Neuromotor development in relation to birth weight in rabbits.

PubMed

Harel, S; Shapira, Y; Hartzler, J; Teng, E L; Quiligan, E; Van Der Meulen, J P

1978-01-01

The development of neuromotor patterns in relation to birth weight was studied in the rabbit, a perinatal brain developer. In order to induce intrauterine growth retardation and to increase the number of low birth weight rabbits, experimental ischemia to half the fetuses in each doe was achieved by total ligation of approximately 30% of spiral vessels to the placenta, during the last trimester of gestation. Following natural delivery, the rabbit pups were periodically observed for the appearance of eye-opening and righting reflex, and for the cessations of falling, circling and dragging of hind limbs. An index of neuromotor development was assigned to each rabbit by summing up the age (in days) of appearance of each of the neuromotor milestones. An association was found between low birth weight and delayed neuromotor development at 2 weeks of age. The most significant correlation was found between low birth weight and delayed disappearance of falling. The latter may represent incoordination as an expression of cerebellar dysfunction.

Anterior segment parameters of rabbits with rotating Scheimpflug camera.

PubMed

Yüksel, Harun; Türkcü, Fatih M; Ari, Şeyhmus; Çinar, Yasin; Cingü, Abdullah K; Şahin, Muhammed; Şahin, Alparslan; Özkurt, Zeynep; Çaça, İhsan

2015-05-01

Rabbit is one of the most commonly used experimental animals for corneal studies due to similarity of size to human cornea and ease of manipulation. In this study, we assessed anterior segment parameters of the healthy rabbit eyes with Pentacam HR (Oculus, Wetzlar, Germany). Six-month-old, approximately 2.5-3 kg weighted, 30 female New Zealand rabbits were used in the study. Right eye of the each rabbit was imaged with Pentacam HR under intramuscular ketamine hydrochloride (Ketalar; Eczacibasi, Turkey) anesthesia (50 mg/kg). After the imaging, the rabbits with blinking errors, which results in low-quality images, were excluded from the study. Keratometric readings, central corneal thickness (CCT), anterior chamber depth (ACD), and anterior and posterior elevation values, and lens density were noted. In this study, the flattest and the steepest keratometric values were found as 43.34 ± 1.86, 42.7 ± 2.0, and 43.9 ± 1.9 diopters, respectively. The mean CCT and ACD of rabbits were found as 388 ± 39 μm and 2.08 ± 0.16 mm, respectively. Mean of the anterior and posterior elevation at thinnest point was found as 1.29 ± 4.28 and 3.91 ± 6.17 μm, respectively. Keratometric readings and anterior and posterior elevation values of rabbits were similar to human; however, corneal thickness and anterior chamber depth (ACD) values were lower than humans. © 2014 American College of Veterinary Ophthalmologists.

Impact of a gestational exposure to diesel exhaust on offspring gonadal development: experimental study in the rabbit.

PubMed

Bourdon, M; Torres-Rovira, L; Monniaux, D; Faure, C; Levy, R; Tarrade, A; Rousseau-Ralliard, D; Chavatte-Palmer, P; Jolivet, G

2018-06-18

The aim of the present work was to address experimentally the possible impact of exposure to air pollution during gestation on the differentiation and function of the gonads of the offspring using a rabbit model. Rabbits were exposed daily to diluted diesel exhaust gas or filtered air from the 3rd until the 27th day of gestation, during which time germ cells migrate in genital ridges and divide, and fetal sex is determined. Offspring gonads were collected shortly before birth (28th day of gestation) or after puberty (7.5 months after birth). The structure of the gonads was analyzed by histological and immunohistological methods. Serum concentrations of testosterone and anti-Müllerian hormone were determined using ELISA. The morphology and the endocrine function of the gonads collected just at the arrest of the exposure were similar in polluted and control animals in both sexes. No differences were observed as well in gonads collected after puberty. Sperm was collected at the head of the epididymis in adults. Sperm motility and DNA fragmentation were measured. Among all parameters analyzed, only the sperm DNA fragmentation rate was increased three-fold in exposed males. Mechanisms responsible for these modifications and their physiological consequences are to be further clarified.

Risk Factors for Atherosclerosis and the Development of Pre-Atherosclerotic Intimal Hyperplasia

PubMed Central

Cizek, Stephanie M.; Bedri, Shahinaz; Talusan, Paul; Silva, Nilsa; Lee, Hang; Stone, James R.

2007-01-01

Summary Intimal hyperplasia or thickening is considered to be the precursor lesion for atherosclerosis in humans; however the factors governing its formation are unclear. In the atherosclerosis-resistant internal thoracic artery, pre-atherosclerotic intimal hyperplasia routinely forms during adulthood after the 4th decade and is associated with at least two traditional risk factors for atherosclerosis: age and smoking. Background Intimal hyperplasia, or thickening, is considered to be the precursor lesion for atherosclerosis in humans; however, the factors governing its formation are unclear. To gain insight into the etiology of pre-atherosclerotic intimal hyperplasia, traditional risk factors for atherosclerosis were correlated with the intimal hyperplasia in an atherosclerosis-resistant vessel, the internal thoracic artery. Methods Paired internal thoracic arteries were obtained from 89 autopsies. Multivariate logistic regression and multiple regression models were used to examine the association of pre-atherosclerotic intimal hyperplasia with traditional risk factors for atherosclerosis: age, gender, hypertension, smoking, body mass index, diabetes, and hypercholesterolemia. Results Atherosclerotic lesions consisting of fatty streaks and/or type III intermediate lesions were identified in 19 autopsies. Only age >75 years was found to be significantly correlated with atherosclerotic lesion development (P=0.01). Multiple regression model of the intima/media ratio in all 89 cases revealed age >75 years (P<0.0001), age 51–75years (P=0.0012), smoking (P=0.008) and hypertension (P=0.02) to be significantly correlated with intimal thickness. In the 70 cases without atherosclerosis, only age 51–75 years (P=0.006) and smoking (P=0.028) were found to be significantly associated with pre-atherosclerotic intimal thickening. Conclusions In the atherosclerosis-resistant internal thoracic artery, pre-atherosclerotic intimal hyperplasia routinely forms during adulthood

Rabbit analgesia.

PubMed

Barter, Linda S

2011-01-01

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

[Experimental study on loading naringin composite scaffolds for repairing rabbit osteochondral defects].

PubMed

Huang, Junbo; Wang, Shiyong; Zhang, Xiaomin; Li, Gen; Ji, Puzhong; Zhao, Hongbin

2017-04-01

To investigate the performance of loading naringin composite scaffolds and its effects on repair of osteochondral defects. The loading naringin and unloading naringin sustained release microspheres were prepared by W/O/W method; with the materials of the attpulgite and the collagen type I, the loading naringin, unloading naringin, and loading transforming growth factor β 1 (TGF-β 1 ) osteochondral composite scaffolds were constructed respectively by "3 layers sandwich method". The effect of sustained-release of loading naringin microspheres, the morphology of the composite scaffolds, and the biocompatibility were evaluated respectively by releasing in vitro , scanning electron microscope, and cell counting kit 8. Forty Japanese white rabbits were randomly divided into groups A, B, C, and D, 10 rabbits each group. After a osteochondral defect of 4.5 mm in diameter and 4 mm in depth was made in the intercondylar fossa of two femurs. Defect was not repaired in group A (blank control), and defect was repaired with unloading naringin composite scaffolds (negative control group), loading naringin composite scaffolds (experimental group), and loading TGF-β 1 composite scaffolds (positive control group) in groups B, C, and D respectively. At 3 and 6 months after repair, the intercondylar fossa was harvested for the general, HE staining, and toluidine blue staining to observe the repair effect. Western blot was used to detect the expression of collagen type II in the new cartilage. Loading naringin microspheres had good effect of sustained-release; the osteochondral composite scaffolds had good porosity; the cell proliferation rate on loading naringin composite scaffold was increased significantly when compared with unloading naringin scaffold ( P <0.05). General observation revealed that defect range of groups C and D was reduced significantly when compared with groups A and B at 3 months after repair; at 6 months after repair, defects of group C were covered by new

Lipid metabolism abnormalities in alcohol-treated rabbits: a morphometric and haematologic study comparing high and low alcohol doses.

PubMed

Ikemura, Satoshi; Yamamoto, Takuaki; Motomura, Goro; Iwasaki, Kenyu; Yamaguchi, Ryosuke; Zhao, Garida; Iwamoto, Yukihide

2011-08-01

The pathogenesis of alcohol-induced osteonecrosis remains unclear. The purpose of the present study was to evaluate the morphological changes in bone marrow fat cells and the changes in the serum lipid levels in alcohol-treated rabbits. Fifteen rabbits were randomly assigned into three groups: Four rabbits intragastrically received low-dose alcohol (LDA) (15 ml/kg per day) containing 15% ethanol for 4 weeks, five rabbits received high-dose alcohol (HDA) (30 ml/kg per day) for 4 weeks and six rabbits received physiologic saline for 4 weeks as a control group. Six weeks after the initial alcohol administration, all rabbits were sacrificed. The mean size of the bone marrow fat cells in rabbits treated with HDA was significantly larger than that in the control group (P = 0.0001). Haematologically, the levels of triglycerides and free fatty acids in the rabbits treated with both low-dose and HDA were significantly higher than those in the control group (P = 0.001 for both comparisons). The results of this study are that there are lipid metabolism abnormalities, both morphologically and haematologically, after alcohol administration. Also these findings were more apparent in rabbits treated with HDA than those treated with LDA. © 2011 The Authors. International Journal of Experimental Pathology © 2011 International Journal of Experimental Pathology.

Rosuvastatin reduces atherosclerotic lesions and promotes progenitor cell mobilisation and recruitment in apolipoprotein E knockout mice.

PubMed

Schroeter, Marco R; Humboldt, Tim; Schäfer, Katrin; Konstantinides, Stavros

2009-07-01

Statins enhance incorporation of bone marrow-derived cells into experimental neointimal lesions. However, the contribution of progenitor cells to progression of spontaneous atherosclerotic plaques, and the possible modulatory role of statins in this process, remain poorly understood. We compared the effects of rosuvastatin (1 and 10mg/kg BW) and pravastatin (10mg/kg) on progenitor cell mobilisation, recruitment into atherosclerotic plaques, and lesion growth. Statins were administered over 8 weeks to apolipoprotein E knockout mice on atherogenic diet. In addition, mice were lethally irradiated, followed by transplantation of bone marrow from LacZ transgenic mice. Rosuvastatin reduced lesion area and intima-to-media ratio at the brachiocephalic artery compared to vehicle, while both parameters were not significantly altered by pravastatin. Rosuvastatin also augmented endothelialisation (P<0.05) and reduced the smooth muscle cells (SMC) content (P=0.042) of lesions. Numbers of c-kit, sca-1 and flk-1, sca-1 double-positive progenitor cells were significantly increased in rosuvastatin compared to control-treated mice, both in the bone marrow and the peripheral blood. Similarly, the number of spleen-derived acLDL, lectin double-positive progenitor cells (P=0.001) and colony-forming units (P=0.0104) was significantly increased in mice treated with rosuvastatin compared to vehicle alone. In the bone marrow, increased Akt and p42/44 MAP kinase phosphorylation and upregulated SDF1alpha mRNA expression were observed. Importantly, rosuvastatin treatment also increased the plasma levels of c-kit ligand (P=0.003), and the number of c-kit-positive cells within atherosclerotic lesions (P=0.041). Our findings suggest that rosuvastatin reduces the size of atherosclerotic plaques, and this effect appears to involve progenitor cell mobilisation and recruitment into vascular lesions.

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

Flow in Atherosclerotic Blood Vessels

NASA Astrophysics Data System (ADS)

Berger, Stanley A.; Stroud, Jenn S.

2000-11-01

Atherosclerotic lesions occur in arteries where there are major changes in flow structure, e.g. bifurcations and junctions. The reduction of vessel lumen alters the flow, including the mechanical forces on the walls. We have examined the flow in carotid artery bifurcations with realistic plaque contours. The unsteady, incompressible, Navier-Stokes equations are solved in finite-volume form. Steady and pulsatile flows have been analyzed for laminar and turbulent flows, using for the latter a low-Reynolds number k- ɛ model and a k-ω model. Non-Newtonian viscosity is also considered using a power-law model. In general the very irregular contours of the vessels lead to recirculating regions, strong spatial variations of wall shear stresses, and in some cases, vortex shedding. Even steady inlet flow exhibits fluctuating, unsteady behavior. Neither turbulence models captures all the physics of the flow. The flow, in fact, appears to be transitional and not fully turbulent. For unsteady flow, there are also strong temporal variations of normal and shear stresses, which together with the strong spatial variations, has important implications for the onset and progression of atherosclerotic disease.

Label-free imaging of atherosclerotic plaques using third-harmonic generation microscopy

PubMed Central

Small, David M.; Jones, Jason S.; Tendler, Irwin I.; Miller, Paul E.; Ghetti, Andre; Nishimura, Nozomi

2017-01-01

Multiphoton microscopy using laser sources in the mid-infrared range (MIR, 1,300 nm and 1,700 nm) was used to image atherosclerotic plaques from murine and human samples. Third harmonic generation (THG) from atherosclerotic plaques revealed morphological details of cellular and extracellular lipid deposits. Simultaneous nonlinear optical signals from the same laser source, including second harmonic generation and endogenous fluorescence, resulted in label-free images of various layers within the diseased vessel wall. The THG signal adds an endogenous contrast mechanism with a practical degree of specificity for atherosclerotic plaques that complements current nonlinear optical methods for the investigation of cardiovascular disease. Our use of whole-mount tissue and backward scattered epi-detection suggests THG could potentially be used in the future as a clinical tool. PMID:29359098

Association between abdominal fat distribution and atherosclerotic changes in the carotid artery.

PubMed

Oike, Miki; Yokokawa, Hirohide; Fukuda, Hiroshi; Haniu, Tomomi; Oka, Fukuko; Hisaoka, Teruhiko; Isonuma, Hiroshi

2014-01-01

We aimed to evaluate the association between abdominal fat distribution (e.g., abdominal visceral fat area [VFA], subcutaneous fat area [SFA], and total fat area [TFA]), waist circumference (WC), or body mass index (BMI) and atherosclerotic changes in the carotid artery after adjusting for common risk factors. The present study is a hospital-based, cross-sectional study. Study participants included 223 Japanese individuals who underwent a medical health checkup at Juntendo University Hospital, Tokyo, between December 2005 and August 2011. Multivariate logistic regression analysis was used to examine the association between abdominal VFA, SFA, TFA, the VFA/SFA ratio, WC, or BMI and intima-media thickness [IMT] (mean IMT≥1.1mm or maximum IMT≥1.2mm) as atherosclerotic changes in the carotid artery. Multivariate logistic regression analysis showed that VFA (OR for ≥150cm(2) versus <100cm(2), 3.88; 95% CI, 1.39-10.85), BMI (OR for ≥27.6kg/m(2) versus <25kg/m(2), 5.22; 95% CI, 1.69-16.16), and TFA (OR for 200-285cm(2) versus <200cm(2), 4.15; 95% CI, 1.34-12.86: OR for ≥285cm(2) versus <200cm(2), 5.53; 95% CI, 1.76-17.35) were significantly associated with atherosclerotic changes in men. After adjustment for BMI, only TFA (OR for ≥285cm(2) versus <200cm(2), 3.76; 95%CI, 1.03-13.79) in men was significantly associated with atherosclerotic changes in the carotid artery. Our results indicate that VFA, TFA, and BMI are independently associated with atherosclerotic changes in Japanese men. TFA may be considered as a valuable measure of atherosclerotic changes. Copyright © 2013 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Texture based segmentation method to detect atherosclerotic plaque from optical tomography images

NASA Astrophysics Data System (ADS)

Prakash, Ammu; Hewko, Mark; Sowa, Michael; Sherif, Sherif

2013-06-01

Optical coherence tomography (OCT) imaging has been widely employed in assessing cardiovascular disease. Atherosclerosis is one of the major cause cardio vascular diseases. However visual detection of atherosclerotic plaque from OCT images is often limited and further complicated by high frame rates. We developed a texture based segmentation method to automatically detect plaque and non plaque regions from OCT images. To verify our results we compared them to photographs of the vascular tissue with atherosclerotic plaque that we used to generate the OCT images. Our results show a close match with photographs of vascular tissue with atherosclerotic plaque. Our texture based segmentation method for plaque detection could be potentially used in clinical cardiovascular OCT imaging for plaque detection.

Collagen and related extracellular matrix proteins in atherosclerotic plaque development.

PubMed

Shami, Annelie; Gonçalves, Isabel; Hultgårdh-Nilsson, Anna

2014-10-01

The structure, composition and turnover of the extracellular matrix (ECM) as well as cell-matrix interactions are crucial in the developing atherosclerotic plaque. There is a need for further insight into specific proteins in the ECM and their functions in the developing plaque, and during the last few years a number of publications have highlighted this very important field of research. These novel findings will be addressed in the present review. This review covers literature focused on collagen and ECM proteins interacting with collagen, and what their roles may be in plaque development. Acute myocardial infarction and stroke are common diseases that cause disability and mortality, and the underlying mechanism is often the rupture of a vulnerable atherosclerotic plaque. The vascular ECM and the tissue repair in the atherosclerotic lesion are important players in plaque progression. Understanding how specific proteins in the ECM interact with cells in the plaque and affect the fate of the plaque can lead to new treatments for cardiovascular disease.

Evaluation of clinical and paraclinical effects of intraosseous vs intravenous administration of propofol on general anesthesia in rabbits

PubMed Central

Mazaheri-Khameneh, Ramin; Sarrafzadeh-Rezaei, Farshid; Asri-Rezaei, Siamak; Dalir-Naghadeh, Bahram

2012-01-01

This prospective study aimed to compare the intraosseous (IO) and intravenous (IV) effects of propofol on selected blood parameters and physiological variables during general anesthesia in rabbits. Thirty New Zealand White rabbits were studied. Six rabbits received IV propofol (group 1) and another 6 rabbits, were injected propofol intraosseously (Group 2) for 30 minutes (experimental groups). Rabbits of the third and fourth groups received IV and IO normal saline at the same volume given to the experimental groups, respectively. In the fifth group IO cannulation was performed but neither propofol nor normal saline were administered. Blood profiles were assayed before induction and after recovery of anesthesia. Heart and respiratory rates, rectal temperature, saturation of peripheral oxygen and mean arterial blood pressure were recorded. Heart rate increased significantly 1 to 5 minutes after induction of anesthesia in experimental groups (P < 0.05). Although mean arterial blood pressure decreased significantly from baseline, values remained above 60 mm Hg (P < 0.05). Respiratory rate decreased significantly in experimental groups, but remained higher in group 2 (P < 0.05). The lymphocyte count decreased significantly in group 1 (P < 0.05). The concentration of alkaline phosphatase in all rabbits, aspartate aminotransferase and gamma-glutamyl transferase in the first group and gamma-glutamyl transferase in the third group increased significantly (P < 0.05). Total bilirubin decreased significantly in group 2 (P < 0.05). All measured values remained within normal limits. Based on the least significant physiological, hematological and biochemical effects, the IO injection of propofol appears to be safe and suitable method of anesthesia in rabbits with limited vascular access. PMID:25653755

Evaluation of clinical and paraclinical effects of intraosseous vs intravenous administration of propofol on general anesthesia in rabbits.

PubMed

Mazaheri-Khameneh, Ramin; Sarrafzadeh-Rezaei, Farshid; Asri-Rezaei, Siamak; Dalir-Naghadeh, Bahram

2012-01-01

This prospective study aimed to compare the intraosseous (IO) and intravenous (IV) effects of propofol on selected blood parameters and physiological variables during general anesthesia in rabbits. Thirty New Zealand White rabbits were studied. Six rabbits received IV propofol (group 1) and another 6 rabbits, were injected propofol intraosseously (Group 2) for 30 minutes (experimental groups). Rabbits of the third and fourth groups received IV and IO normal saline at the same volume given to the experimental groups, respectively. In the fifth group IO cannulation was performed but neither propofol nor normal saline were administered. Blood profiles were assayed before induction and after recovery of anesthesia. Heart and respiratory rates, rectal temperature, saturation of peripheral oxygen and mean arterial blood pressure were recorded. Heart rate increased significantly 1 to 5 minutes after induction of anesthesia in experimental groups (P < 0.05). Although mean arterial blood pressure decreased significantly from baseline, values remained above 60 mm Hg (P < 0.05). Respiratory rate decreased significantly in experimental groups, but remained higher in group 2 (P < 0.05). The lymphocyte count decreased significantly in group 1 (P < 0.05). The concentration of alkaline phosphatase in all rabbits, aspartate aminotransferase and gamma-glutamyl transferase in the first group and gamma-glutamyl transferase in the third group increased significantly (P < 0.05). Total bilirubin decreased significantly in group 2 (P < 0.05). All measured values remained within normal limits. Based on the least significant physiological, hematological and biochemical effects, the IO injection of propofol appears to be safe and suitable method of anesthesia in rabbits with limited vascular access.

Decreased cathepsin K levels in human atherosclerotic plaques are associated with plaque instability.

PubMed

Zhao, Huiying; Qin, Xiujiao; Wang, Shuai; Sun, Xiwei; Dong, Bin

2017-10-01

Investigating the determinants and dynamics of atherosclerotic plaque instability is a key area of current cardiovascular research. Extracellular matrix degradation from excessive proteolysis induced by enzymes such as cathepsin K (Cat K) is implicated in the pathogenesis of unstable plaques. The current study assessed the expression of Cat K in human unstable atherosclerotic plaques. Specimens of popliteal arteries with atherosclerotic plaques were classified as stable (<40% lipid core plaque area; n=6) or unstable (≥40% lipid core plaque area; n=14) based on histopathological examinations of hematoxylin and eosin stained sections. The expression of Cat K and cystatin C (Cys C) were assessed by immunohistochemical examination and levels of Cat K mRNA were detected by semi-quantitative reverse transcriptase polymerase chain reaction. Morphological changes including a larger lipid core, endothelial proliferation with foam cells and destruction of internal elastic lamina were observed in unstable atherosclerotic plaques. In unstable plaques, the expression of Cat K protein and mRNA was upregulated, whereas Cys C protein expression was downregulated. The interplay between Cat K and Cys C may underlie the progression of plaques from stable to unstable and the current study indicated that Cat K and Cys C are potential targets for preventing and treating vulnerable atherosclerotic plaque ruptures.

[Morphologic study of the intestine in an experimental model of amnioinfusion in fetal rabbits with gastroschisis].

PubMed

Muñoz, M E; Albert, A; Juliá, V; Sancho, M A; Grande, C; Martínez, A; Morales, L

2002-10-01

An experimental model of serial amnioinfusion has been developed in fetal rabbits with gastroschisis, using an intraamniotic catheter connected to a subcutaneous port. Fetuses of 4 groups were compared 7 days after surgery: group A: gastroschisis and daily amnioinfusion through an implanted catheter; group C: gastroschisis and blind amniotic catheter; group G: gastroschisis without catheter; group O: nonoperated fetuses. Survival rate, fetal body weight, lung weight, intestinal weight and length were determined. Computer aided morphometric analysis was performed, in which intestinal diameter, thickness and villi length were measured. Amniotic fluid samples were recovered along the experimental period. Intestinal length was significantly shorter and had a significantly thicker wall than nonoperated fetuses; we found no other morphometric differences between gastroschisis treated with amnioinfusion (group A) and the other gastroschisis groups (C and G). Amnioinfusion did not affect fetal survival rate; the amniotic catheter alone did not cause pulmonary hypoplasia due to significant amniotic leak. The physiological decrease in amniotic volume towards the end of gestation has not been modified by this regime of amnioinfusion.

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

PubMed Central

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

2015-01-01

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

An Experimental Model of Diet-Induced Metabolic Syndrome in Rabbit: Methodological Considerations, Development, and Assessment.

PubMed

Arias-Mutis, Óscar Julián; Genovés, Patricia; Calvo, Conrado J; Díaz, Ana; Parra, Germán; Such-Miquel, Luis; Such, Luis; Alberola, Antonio; Chorro, Francisco Javier; Zarzoso, Manuel

2018-04-20

In recent years, obesity and metabolic syndrome (MetS) have become a growing problem for public health and clinical practice, given their increased prevalence due to the rise of sedentary lifestyles and unhealthy eating habits. Thanks to animal models, basic research can investigate the mechanisms underlying pathological processes such as MetS. Here, we describe the methods used to develop an experimental rabbit model of diet-induced MetS and its assessment. After a period of acclimation, animals are fed a high-fat (10% hydrogenated coconut oil and 5% lard), high-sucrose (15% sucrose dissolved in water) diet for 28 weeks. During this period, several experimental procedures were performed to evaluate the different components of MetS: morphological and blood pressure measurements, glucose tolerance determination, and the analysis of several plasma markers. At the end of the experimental period, animals developed central obesity, mild hypertension, pre-diabetes, and dyslipidemia with low HDL, high LDL, and an increase of triglyceride (TG) levels, thus reproducing the main components of human MetS. This chronic model allows new perspectives for understanding the underlying mechanisms in the progression of the disease, the detection of preclinical and clinical markers that allow the identification of patients at risk, or even the testing of new therapeutic approaches for the treatment of this complex pathology.

CML/CD36 accelerates atherosclerotic progression via inhibiting foam cell migration.

PubMed

Xu, Suining; Li, Lihua; Yan, Jinchuan; Ye, Fei; Shao, Chen; Sun, Zhen; Bao, Zhengyang; Dai, Zhiyin; Zhu, Jie; Jing, Lele; Wang, Zhongqun

2018-01-01

Among the various complications of type 2 diabetes mellitus, atherosclerosis causes the highest disability and morbidity. A multitude of macrophage-derived foam cells are retained in atherosclerotic plaques resulting not only from recruitment of monocytes into lesions but also from a reduced rate of macrophage migration from lesions. Nε-carboxymethyl-Lysine (CML), an advanced glycation end product, is responsible for most complications of diabetes. This study was designed to investigate the mechanism of CML/CD36 accelerating atherosclerotic progression via inhibiting foam cell migration. In vivo study and in vitro study were performed. For the in vivo investigation, CML/CD36 accelerated atherosclerotic progression via promoting the accumulation of macrophage-derived foam cells in aorta and inhibited macrophage-derived foam cells in aorta migrating to the para-aorta lymph node of diabetic apoE -/- mice. For the in vitro investigation, CML/CD36 inhibited RAW264.7-derived foam cell migration through NOX-derived ROS, FAK phosphorylation, Arp2/3 complex activation and F-actin polymerization. Thus, we concluded that CML/CD36 inhibited foam cells of plaque migrating to para-aorta lymph nodes, accelerating atherosclerotic progression. The corresponding mechanism may be via free cholesterol, ROS generation, p-FAK, Arp2/3, F-actin polymerization. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Efficacy of humanlike Augmentin SR (2000/125 mg) twice daily treatment on Haemophilus influenzae experimental pneumonia in rabbits.

PubMed

Croisier, Delphine; Benoit, Martha; Durand, David; Lequeu, Catherine; Piroth, Lionel; Portier, Henri; Chavanet, Pascal

2007-01-01

We investigated the efficacy of 2 formulations of Augmentin on experimental pneumonia due to Haemophilus influenzae (HI) in rabbits. Two strains were used (H128 and 401285) with amoxicillin/clavulanic acid MICs of 1/0.5 mg/l and 4/2 mg/l. Pneumonia was induced in immunocompetent rabbits by inoculation of 10 log(10) CFU HI. The treatments were infused by using computer controlled pumps in order to mimic the human pharmacokinetic (PK) profile of either conventional Augmentin treatment (875/125 mg twice daily) or the sustained release formulation (SR: 2000/125 mg twice daily). After 2 d of treatment, the bacterial concentrations in the lungs were similar for both strains and both treatments: isolate H128, conventional Augmentin reduced bacterial numbers to 3.8+/-2.1 log(10) CFU/g and Augmentin SR to 3.1+/-2.4 log(10) CFU/g; isolate 401285, conventional Augmentin to 3.5+/-2. Thus, both treatments demonstrated similar efficacy against H. influenzae pneumonia in this model, even when induced by a strain with an amoxicillin/clavulanic acid MIC of 4/2 mg/l. These results support current breakpoints for conventional Augmentin against H. influenzae and suggest that Augmentin SR is at least as effective against these isolates.

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

Recombinant vaccine displaying the loop-neutralizing determinant from protective antigen completely protects rabbits from experimental inhalation anthrax.

PubMed

Oscherwitz, Jon; Yu, Fen; Jacobs, Jana L; Cease, Kemp B

2013-03-01

We previously showed that a multiple antigenic peptide (MAP) vaccine displaying amino acids (aa) 304 to 319 from the 2β2-2β3 loop of protective antigen was capable of protecting rabbits from an aerosolized spore challenge with Bacillus anthracis Ames strain. Antibodies to this sequence, referred to as the loop-neutralizing determinant (LND), are highly potent at neutralizing lethal toxin yet are virtually absent in rabbit and human protective antigen (PA) antiserum. While the MAP vaccine was protective against anthrax, it contains a single heterologous helper T cell epitope which may be suboptimal for stimulating an outbred human population. We therefore engineered a recombinant vaccine (Rec-LND) containing two tandemly repeated copies of the LND fused to maltose binding protein, with enhanced immunogenicity resulting from the p38/P4 helper T cell epitope from Schistosoma mansoni. Rec-LND was found to be highly immunogenic in four major histocompatibility complex (MHC)-diverse strains of mice. All (7/7) rabbits immunized with Rec-LND developed high-titer antibody, 6 out of 7 developed neutralizing antibody, and all rabbits were protected from an aerosolized spore challenge of 193 50% lethal doses (LD(50)) of the B. anthracis Ames strain. Survivor serum from Rec-LND-immunized rabbits revealed significantly increased neutralization titers and specific activity compared to prechallenge levels yet lacked PA or lethal factor (LF) antigenemia. Control rabbits immunized with PA, which were also completely protected, appeared sterilely immune, exhibiting significant declines in neutralization titer and specific activity compared to prechallenge levels. We conclude that Rec-LND may represent a prototype anthrax vaccine for use alone or potentially combined with PA-containing vaccines.

Effects of genipin corneal crosslinking in rabbit corneas.

PubMed

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

2016-07-01

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

Multiple Natural and Experimental Inflammatory Rabbit Lacrimal Gland Phenotypes

PubMed Central

Mircheff, Austin K.; Wang, Yanru; Schechter, Joel E.; Li, Meng; Tong, Warren; Attar, Mayssa; Chengalvala, Murty; Harmuth, Joe; Prusakiewicz, Jeffery J.

2016-01-01

Purpose To investigate lacrimal gland (LG) immunophysiological and immune-mediated inflammatory process (IMIP) phenotype diversity. Methods Ex vivo matured dendritic cells (mDC) were loaded with acinar cell microparticles (MP). Peripheral blood lymphocytes (PBL) were activated in mixed cell reactions with mDC and injected directly into autologous, unilateral LG (1° ATD-LG) of two rabbit cohorts, one naïve, one immunized with a LG lysate membrane fraction (Pi). Autoimmune IgG titers were assayed by ELISA, MCR PBL stimulation indices (SI) by [3H]-thymidine incorporation. Schirmer tests without and with topical anesthetic (STT-I, STT-IA) and rose Bengal (RB) staining tests were performed. H&E and immunohistochemically stained sections were examined. RNA yields and selected transcript abundances were measured. Immune cell number and transcript abundance data were submitted to Principal Component Analysis (PCA). Results Immunizing Pi dose influenced SI but not IgG titers. STT scores were decreased, and rose Bengal scores increased, by day 118 after immunization. Previous immunization exacerbated scores in 1° ATD-eyes and exacerbated 1° ATD-LG atrophy. IMIP were evident in 2° ATD-LG as well as 1° ATD-LG. PCA described diverse immunophysiological phenotypes in control LG and diverse IMIP phenotypes in ATD-LG. IgG titers and SI pre-adoptive transfer were significantly associated with certain post-adoptive transfer IMIP phenotype features, and certain LG IMIP features were significantly associated with RB and STT IA scores. Conclusions The underlying variability of normal states may contribute to the diversity of experimental IMIP phenotypes. The ability to generate and characterize diverse phenotypes may lead to phenotype-specific diagnostic and therapeutic paradigms. PMID:27423911

Quantitative analysis of the polarization characteristics of atherosclerotic plaques

NASA Astrophysics Data System (ADS)

Gubarkova, Ekaterina V.; Kirillin, Michail Y.; Dudenkova, Varvara V.; Kiseleva, Elena B.; Moiseev, Alexander A.; Gelikonov, Grigory V.; Timofeeva, Lidia B.; Fiks, Ilya I.; Feldchtein, Felix I.; Gladkova, Natalia D.

2016-04-01

In this study we demonstrate the capability of cross-polarization optical coherence tomography (CP OCT) to assess collagen and elastin fibers condition in atherosclerotic plaques basing on ratio of the OCT signal levels in cross- and co- polarizations. We consider the depolarization factor (DF) and the effective birefringence (Δn) as quantitative characteristics of CP OCT images. We revealed that calculation of both DF and Δn in the region of interest (fibrous cap) yields a statistically significant difference between stable and unstable plaques (0.46+/-0.21 vs 0.09+/-0.04 for IDF; (4.7+/-1.0)•10-4 vs (2.5+/-0.7)•10-4 for Δn p<0.05). In parallel with CP OCT we used the nonlinear microscopy for analysis of thin cross-section of atherosclerotic plaque, revealing the different average isotropy index of collagen and elastin fibers for stable and unstable plaques (0.30 +/- 0.10 vs 0.70 +/- 0.08; p<0.001). The proposed approach for quantitative assessment of CP OCT images allows cross-scattering and birefringence characterization of stable and unstable atherosclerotic plaques.

Severe maternal undernutrition and post-weaning behavior of rabbits.

PubMed

Simitzis, Panagiotis E; Symeon, George K; Kominakis, Antonios P; Bizelis, Iosif A; Chadio, Stella E; Abas, Zafeiris; Deligeorgis, Stelios G

2015-03-15

The objective of the present experiment was to investigate the implications of severe maternal undernutrition on the post-weaning behavior of rabbits. Thirty two does were randomly assigned to four groups: the control group (C) that was fed 100% of the recommended energy maintenance requirements throughout pregnancy and lactation and the U1, U2 and U3 groups that were fed 50% of the recommended energy maintenance requirements between the 6th and the 19th day of pregnancy, between the 20th and the 27th day of pregnancy and between the 3rd and the 10th day of lactation, respectively. At the age of 50 and 65 days, behavior of rabbits in cages was recorded and rabbits were further subjected to an open-field test; a paradigm used as an indicator of fear and emotional distress. Significant differences were found between the U2 and the other experimental groups for the duration of eating and drinking, and duration of locomotory and investigatory behaviors (P<0.05). At the age of 65 days, duration of comfort behaviors was also lower in the U2 compared to the other groups (P<0.05). On the other hand, duration of resting appeared to be the highest in the group of rabbits born from undernourished does between the 20th and the 27th day of pregnancy (P<0.05). Duration of resting was significantly increased, although frequency and duration of eating and drinking were significantly decreased at the age of 65 days (P<0.05). Male rabbits had greater values for locomotory and investigatory behaviors, and duration of eating and drinking compared to the females (P<0.01). A decreased activity of rabbits during the light period was observed (as expected), whereas an increase in duration of locomotory and investigatory behaviors was observed during the first four and the last 4h of the light and dark periods, respectively (P<0.05). Rabbits born from the U1 and U2 group of does displayed increased rates of latency to leave the start position compared to the other groups during the

The rabbit as an experimental model for biopharmaceutical studies following rectal administration of theophylline.

PubMed

Van Aerde, P; Moerman, E; Van Severen, R; Braeckman, P

1984-03-01

In order to find a suitable animal model for biopharmaceutical studies after rectal application of theophylline, the pharmacokinetics of theophylline following the administration in rabbits of three different rectal preparations were examined and compared with those of the oral and i. v. route. No significant formulation related impact from the studied rectal dosage forms on the bioavailability of the drug was found. However, the unexpected rapid achievement of peak serum concentration after insertion of the suppository lacked any correlation with human experiments. It was concluded that the evaluation of rectal theophylline medication for man cannot directly be based on the data obtained from rabbits.

Patella morphological alteration after patella instability in growing rabbits.

PubMed

Niu, Jinghui; Qi, Qi; Niu, Yingzhen; Dong, Conglei; Dong, Zhenyue; Cui, Peng; Wang, Fei

2017-07-11

The shape of the patella has been considered to be a predisposing factor resulting in patellar instability, but the effects of abnormal patella position during its development are unclear. The present study evaluated patellar morphological changes after patella instability and evaluated the influence of patellar instability on the patella shape. Twenty rabbits that were 2 months old were included in the study. The left knee of each rabbit, defined as the experimental group (N = 20 knees/group), underwent a medial soft tissue restraint release. The right knee of each rabbit, defined as the control group (N = 20 knees/group), did not undergo any surgical procedures. A CT scan was performed on each knee before surgery and 6 months post-surgery to measure the transverse diameter, thickness, Wiberg index, and Wiberg angle for analysis of the patellar morphological changes. Cross-specimen examination was conducted to evaluate the differences between the experimental group and the control group. The four indices remained the same between the two groups before surgery. However, 6 months after surgery, the mean transverse diameter of the patellae in the experimental group was significantly longer than that in the control group (P < 0.001), while the mean thickness in the experimental group was not significantly greater than that in the control group (P = 0.314), resulting in a flattened shape. The Wiberg indices were not significantly different between the two groups. However, the mean Wiberg angle was higher in the experimental group than in the control group (P < 0.001), which resulted in a flattened articular surface of the patella. The sectional shape and articular surface of the patella became more flattened after patella instability in this study, which indicates that patella dysplasia could be caused by patella instability. Clinically, early intervention for adolescent patients with patella instability is important.

Oral Transmucosal Detomidine Gel in New Zealand White Rabbits (Oryctolagus cuniculus)

PubMed Central

Williams, Morika D; Long, C Tyler; Durrant, Jessica R; McKeon, Gabriel P; Shive, Heather R; Griffith, Emily H; Messenger, Kristen M; Fish, Richard E

2017-01-01

Handling and restraining rabbits for routine procedures may be impossible without prior sedation, result in unnecessary stress or injury to the rabbit or handler, and increase experimental variability. Parenteral administration of sedatives can cause stress also, as well as localized pain and tissue damage, especially in fractious animals. Detomidine hydrochloride, an α2-adrenergic receptor agonist, is commercially available in an oral transmucosal (OTM) gel formulation that is FDA-approved for sedation and restraint in horses. This study investigated the efficacy and safety of detomidine gel as an alternative to injectable sedation in rabbits. Eight adult male New Zealand White rabbits each received 0.6, 1.2, or 1.8 mg/kg OTM detomidine gel. Physiologic parameters and sedation scores (SS) were assessed at 10-min intervals from before administration until 100 min afterward. Histopathology of cardiac tissue was scored through 12 d after dosing. Gel administration increased the SS in all rabbits, but none of the animals developed clinically effective sedation (SS of 10 or greater, based on 5 reflex responses on a 3- or 4-point scale). The SS did not differ among dosage groups, and the time–dose interaction was not statistically significant. Heart rate decreased rapidly in all rabbits, with no difference among dosage groups, and there was no effect of time or dosage on peripheral capillary oxygen saturation. Minimal to mild degenerative changes were seen in the myocardium of all treated rabbits, but myocyte necrosis, inflammation, fibrosis, and mural thrombi—reported previously in rabbits that had received parenteral detomidine—did not occur. OTM detomidine gel was safely and easily administered to rabbits, but the duration and level of sedation were unpredictable. The use of OTM detomidine as a sole agent to facilitate handling and restraint of rabbits does not offer advantages over existing parenteral regimens. PMID:28724493

Oral Transmucosal Detomidine Gel in New Zealand White Rabbits (Oryctolagus cuniculus).

PubMed

Williams, Morika D; Long, C Tyler; Durrant, Jessica R; McKeon, Gabriel P; Shive, Heather R; Griffith, Emily H; Messenger, Kristen M; Fish, Richard E

2017-07-01

Handling and restraining rabbits for routine procedures may be impossible without prior sedation, result in unnecessary stress or injury to the rabbit or handler, and increase experimental variability. Parenteral administration of sedatives can cause stress also, as well as localized pain and tissue damage, especially in fractious animals. Detomidine hydrochloride, an α2-adrenergic receptor agonist, is commercially available in an oral transmucosal (OTM) gel formulation that is FDA-approved for sedation and restraint in horses. This study investigated the efficacy and safety of detomidine gel as an alternative to injectable sedation in rabbits. Eight adult male New Zealand White rabbits each received 0.6, 1.2, or 1.8 mg/kg OTM detomidine gel. Physiologic parameters and sedation scores (SS) were assessed at 10-min intervals from before administration until 100 min afterward. Histopathology of cardiac tissue was scored through 12 d after dosing. Gel administration increased the SS in all rabbits, but none of the animals developed clinically effective sedation (SS of 10 or greater, based on 5 reflex responses on a 3- or 4-point scale). The SS did not differ among dosage groups, and the time-dose interaction was not statistically significant. Heart rate decreased rapidly in all rabbits, with no difference among dosage groups, and there was no effect of time or dosage on peripheral capillary oxygen saturation. Minimal to mild degenerative changes were seen in the myocardium of all treated rabbits, but myocyte necrosis, inflammation, fibrosis, and mural thrombi-reported previously in rabbits that had received parenteral detomidine-did not occur. OTM detomidine gel was safely and easily administered to rabbits, but the duration and level of sedation were unpredictable. The use of OTM detomidine as a sole agent to facilitate handling and restraint of rabbits does not offer advantages over existing parenteral regimens.

Histologic and histomorphometric evaluation of bone regeneration using nanocrystalline hydroxyapatite and human freeze-dried bone graft : An experimental study in rabbit.

PubMed

Sadeghi, Rokhsareh; Najafi, Mohammad; Semyari, Hassan; Mashhadiabbas, Fatemeh

2017-03-01

Bone regeneration is an important concern in periodontal treatment and implant dentistry. Different biomaterials and surgical techniques have been used for this purpose. The aim of the present study was to compare the effect of nanocrystalline hydroxyapatite and human freeze-dried bone graft (FDBG) in regeneration of rabbit calvarium bony defects by histologic and histomorphometric evaluation. In this experimental study, three similar defects, measuring 8 mm in diameter, were created in the calvaria of 16 white New Zealand rabbits. Two defects were filled with FDBG and nanocrystalline hydroxyapatite silica gel, while the other one remained unfilled to be considered as control. All the defects were covered with collagen membranes. During the healing period, two animals perished; so 14 rabbits were divided into two groups: half of them were euthanized after 6 weeks of healing and the other half after 12 weeks. The specimens were subjected to histologic and histomorphometric examinations for assessment of the following variables: percentage of bone formation and residual graft material, inflammation scores, patterns of bone formation and type of newly formed bone. The percentages of new bone formation after 6 weeks were 14.22 ± 7.85, 21.57 ± 6.91, and 20.54 ± 10.07% in FDBG, NanoBone, and control defects. These values were 27.54 ± 20.19, 23.86 ± 6.27, and 26.48 ± 14.18% in 12-week specimens, respectively. No significant differences were found in the amount of bone formation between the groups. With regard to inflammation, the control and NanoBone groups showed significantly less inflammation compared to FDBG at the 6-week healing phase (P = 0.04); this difference was not significant in the 12-week specimens. Based on the results of this experimental study, both NanoBone and FDBG exhibited a similar effect on bone formation.

Effect of hypothyroidism on the purinergic responses of corpus cavernosal smooth muscle in rabbits.

PubMed

Yildirim, M K; Bagcivan, I; Sarac, B; Kilicarslan, H; Yildirim, S; Kaya, T

2008-01-01

Several studies have reported evidence of hormonal abnormalities in 25-35% of impotent men. Hypothyroidism has been reported to occur in 6% of impotent men. In the present study, we examined purinergic relaxation responses in hypothyroidism in an experimental rabbit model and compared them with controls to evaluate the possible involvement of the purinergic pathway. The study comprised 20 male New Zealand white rabbits. The rabbits were divided into two equal groups. We tested the effects of ATP, alpha beta ATP, and adenosine precontracted with phenylephrine on the isolated corpus cavernosum preparations from control and hypothyroid rabbits. We also evaluated the effects of ATP, alpha beta ATP, and adenosine on the cGMP levels in the isolated corpus cavernosum preparations from control and hypothyroid rabbits. T3, T4, and testosterone levels were significantly lower in hypothyroid rabbits. ATP, alpha beta ATP, carbachol, and electrical field stimulation (EFS)-induced frequency-dependent relaxation responses in the isolated rabbit corpus cavernosum strips precontracted with phenylephrine reduced significantly (P<0.05). Adenosine-induced relaxation responses did not change significantly in hypothyroid rabbits. Reduction of relaxation response in hypothyroid rabbits corpus cavernosum can depend on a decreased release of nitric oxide (NO) from nitrergic nerves and endothelium.

Virological and clinico-pathological features of orf virus infection in experimentally infected rabbits and mice.

PubMed

Cargnelutti, J F; Masuda, E K; Martins, M; Diel, D G; Rock, D L; Weiblen, R; Flores, E F

2011-01-01

Many aspects of the biology of orf virus (ORFV) infection remain poorly understood and attempts to establish animal models have yielded conflicting and non-reproducible results. We herein describe the characterization of ORFV infection and disease in rabbits and mice. A protocol of intradermal inoculation was employed to inoculate 10(8.5)TCID₅₀/mL of ORFV strain IA-82 in the skin of ears, of the back and labial commissures. All inoculated rabbits presented a clinical course characterized by erythema, macules, papules/vesicles or pustules that eventually dried originating scabs. Local signs started around days 3 and 4 post-inoculation (pi) and lasted 3-10 days. Virus was recovered from lesions between days 2 and 14pi. Histological examination of lesions revealed focal proliferative dermatitis with ballooning degeneration and eosinophilic intracytoplasmic inclusion bodies in keratinocytes, histological hallmarks of contagious ecthyma in sheep. A similar, albeit milder clinical course occurred in 5/10 inoculated mice; virus was recovered from lesions from three animals. Inoculated lambs - used as controls - developed severe lesions of contagious ecthyma. VN tests performed at day 28pi failed to detect neutralizing antibodies in all inoculated animals. In contrast, convalescent rabbit sera were positive by ELISA at dilutions from 100 to 400. These results show that rabbits are susceptible to ORFV infection and thus may be used to study selected aspects of ORFV biology. Copyright © 2010 Elsevier Ltd. All rights reserved.

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

PubMed

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

2012-04-01

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

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

PubMed

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

2017-04-24

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

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

Diminazene enhances stability of atherosclerotic plaques in ApoE-deficient mice

PubMed Central

Fraga-Silva, Rodrigo A.; Montecucco, Fabrizio; Costa-Fraga, Fabiana P.; Nencioni, Alessio; Caffa, Irene; Bragina, Maiia E.; Mach, François; Raizada, Mohan K.; Santos, Robson A.S.; da Silva, Rafaela F.; Stergiopulos, Nikolaos

2017-01-01

Angiotensin (Ang) II contributes to the development of atherosclerosis, while Ang-(1–7) has atheroprotective actions. Accordingly, angiotensin-converting enzyme 2 (ACE2), which breaks-down Ang II and forms Ang-(1–7), has been suggested as a target against atherosclerosis. Here we investigated the actions of diminazene, a recently developed ACE2 activator compound, in a model of vulnerable atherosclerotic plaque. Atherosclerotic plaque formation was induced in the carotid artery of ApoE-deficient mice by a shear stress (SS) modiffer device. The animals were treated with diminazene (15 mg/kg/day) or vehicle. ACE2 was strongly expressed in the aortic root and low SS-induced carotid plaques, but poorly expressed in the oscillatory SS-induced carotid plaques. Diminazene treatment did not change the lesion size, but ameliorated the composition of aortic root and low SS-induced carotid plaques by increasing collagen content and decreasing both MMP-9 expression and macrophage infiltration. Interestingly, these beneficial effects were not observed in the oscillatory SS-induced plaque. Additionally, diminazene treatment decreased intraplaque ICAM-1 and VCAM-1 expression, circulating cytokine and chemokine levels and serum triglycerides. In summary, ACE2 was distinctively expressed in atherosclerotic plaques, which depends on the local pattern of shear stress. Moreover, diminazene treatment enhances the stability of atherosclerotic plaques. PMID:26304699

Erythrocyte Osmotic Fragility and Excitability Score in Rabbit fed Hibiscus Sabdariffa in Graded Level.

PubMed

Adenkola, A Y; Oluremi, O I A

2014-12-29

This study was conducted for 10 weeks with the aim of investigating the erythrocyte membrane integrity as measured by erythrocyte osmotic fragility and excitability scores of rabbits fed graded level of Hibiscus sabdariffa calyx (HSC). Twenty weaners' rabbit of both sexes were used for the study and were placed on four experimental diets which contain the following percentages of HSC 0 %, 25 %, 50 %, 75 %, as feed additive and were added at 0 g, 62.5 g, 125 g, 187.5 g designated as T1, T2, T3 and T4 experimental diets. Excitability scores were measured weekly as described by Voisnet et al. (1997). At the end of the experiment, the rabbits were slaughtered by severing the jugular vein. A Blood sample (2 ml) was collected from each rabbit into sampled bottles, containing the Na EDTA as anticoagulant for hematological analysis. Packed cell volume (PCV) Haemoglobin concentration (Hb), Total red blood cell (RBC) count, Total leukocyte count as well as differential leukocyte was determined using standard method. The percentage haemolysis recorded at 0.3 % to 0.8 % was significantly (P < 0.05) higher in rabbits in T1 compared to the remaining 3 diets. The result of excitability score shows that rabbit on diet 1 and 2 had a lower value which was significantly (P < 0.05) lower than rabbits on diets 3 and 4 with a value of 65.5 ± 5.0 and 70.00 ± 5.50 % respectively. In conclusion this study demonstrated for the first time that chronic administration of HSC improves haematological parameters, brain mood and function as well as maintaining erythrocyte membrane integrity.

A critical role of platelet adhesion in the initiation of atherosclerotic lesion formation.

PubMed

Massberg, Steffen; Brand, Korbinian; Grüner, Sabine; Page, Sharon; Müller, Elke; Müller, Iris; Bergmeier, Wolfgang; Richter, Thomas; Lorenz, Michael; Konrad, Ildiko; Nieswandt, Bernhard; Gawaz, Meinrad

2002-10-07

The contribution of platelets to the process of atherosclerosis remains unclear. Here, we show in vivo that platelets adhere to the vascular endothelium of the carotid artery in ApoE(-)(/)(-) mice before the development of manifest atherosclerotic lesions. Platelet-endothelial cell interaction involved both platelet glycoprotein (GP)Ibalpha and GPIIb-IIIa. Platelet adhesion to the endothelium coincides with inflammatory gene expression and preceded atherosclerotic plaque invasion by leukocytes. Prolonged blockade of platelet adhesion in ApoE(-)(/)(-) mice profoundly reduced leukocyte accumulation in the arterial intima and attenuated atherosclerotic lesion formation in the carotid artery bifurcation, the aortic sinus, and the coronary arteries. These findings establish the platelet as a major player in initiation of the atherogenetic process.

Revascularization to preserve renal function in patients with atherosclerotic renovascular disease.

PubMed

Novick, A C; Textor, S C; Bodie, B; Khauli, R B

1984-08-01

There are a significant number of patients with advanced atherosclerotic renovascular disease whose blood pressure is well controlled with medical therapy but in whom such vascular disease poses a grave risk to overall renal function. This article reviews current concepts regarding screening, evaluation, and selection of patients with this disease for revascularization to preserve renal function. The underlying rationale for this approach is an increasing awareness that, in selected patients, atherosclerotic renovascular disease represents a surgically correctable cause of progressive renal failure.

Efficacy of topotecan treatment on antioxidant enzymes and TBA-RS levels in submandibular glands of rabbits: an experimental study.

PubMed

Muluk, Nuray Bayar; Kisa, Uçler; Kaçmaz, Murat; Apan, Alpaslan; Koç, Can

2005-01-01

The aim of this study was to investigate the effects of topotecan (Hycamtin), a topoisomerase I inhibiting anticancer agent, on antioxidant enzymes (SOD, CAT, and GSH-Px) and TBA-RS values of the submandibular glands of the rabbits. The study was conveyed in two groups (Group I, II) and control with a total of 24 rabbits. Eight rabbits in group I received intravenous (i.v.) topotecan (0.25 mg/kg once daily) for 3 days. Eight rabbits in group II received i.v. topotecan (0.5 mg/kg once daily) for 3 days. On the 15th day after administration of topotecan, submandibular glands were removed and levels of the SOD, CAT, and GSH-Px and the TBA-RS in the submandibular glands of the rabbits were examined. SOD, CAT, and GSH-Px values were significantly higher in high-dose topotecan group compared to control group (P < 0.05). SOD and TBA-RS values were significantly higher in high-dose topotecan group compared to low-dose topotecan group (P < 0.05). It was concluded that, to prevent the hazardous effects of oxygen free radicals due to topotecan, antioxidant enzymes SOD, CAT, and GSH-Px were increased. The higher levels of the TBA-RS values in group II showed that permanent damage was present because of high-dose topotecan administration in the submandibular glands of the rabbits.

Oral administration of myostatin-specific recombinant Saccharomyces cerevisiae vaccine in rabbit.

PubMed

Liu, Zhongtian; Zhou, Gang; Ren, Chonghua; Xu, Kun; Yan, Qiang; Li, Xinyi; Zhang, Tingting; Zhang, Zhiying

2016-04-29

Yeast is considered as a simple and cost-effective host for protein expression, and our previous studies have proved that Saccharomyces cerevisiae can deliver recombinant protein and DNA into mouse dendritic cells and can further induce immune responses as novel vaccines. In order to know whether similar immune responses can be induced in rabbit by oral administration of such recombinant S. cerevisiae vaccine, we orally fed the rabbits with heat-inactivated myostatin-recombinant S. cerevisiae for 5 weeks, and then myostatin-specific antibody in serum was detected successfully by western blotting and ELISA assay. The rabbits treated with myostatin-recombinant S. cerevisiae vaccine grew faster and their muscles were much heavier than that of the control group. As a common experimental animal and a meat livestock with great economic value, rabbit was proved to be the second animal species that have been successfully orally immunized by recombinant S. cerevisiae vaccine after mice. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

Atherosclerotic plaque characterization by spatial and temporal speckle pattern analysis

NASA Astrophysics Data System (ADS)

Tearney, Guillermo J.; Bouma, Brett E.

2002-04-01

Improved methods are needed to identify the vulnerable coronary plaques responsible for acute myocardial infraction or sudden cardiac death. We describe a method for characterizing the structure and biomechanical properties of atherosclerotic plaques based on speckle pattern fluctuations. Near-field speckle images were acquired from five human aortic specimens ex vivo. The speckle decorrelation time constant varied significantly for vulnerable aortic plaques (τ = 40 ms) versus stable plaques (τ = 400 ms) and normal aorta (τ = 500 ms). These initial results indicate that different atherosclerotic plaque types may be distinguished by analysis of temporal and spatial speckle pattern fluctuations.

TOXEMIA OF PREGNANCY IN THE RABBIT

PubMed Central

Greene, Harry S. N.

1937-01-01

The clinical manifestations and pathology of a disorder associated with pregnancy in the rabbit have been described. The disorder bears a close analogy to toxemia of pregnancy in man and offers an experimental approach to the problems associated with that condition. The evidence at hand indicates that the disorder is of endogenous origin and arises from a disturbance of functions concerned in reproductive processes. PMID:19870636

Zoonoses of rabbits and rodents.

PubMed

Hill, William Allen; Brown, Julie Paige

2011-09-01

Millions of households in the US own rabbits or rodents, including hamsters, guinea pigs, and gerbils. Activities such as hunting and camping also involve human interactions with wild rabbits and rodents. In many environments, feral rabbits and rodents live in close proximity to humans, domesticated animals, and other wildlife. Education of rodent and rabbit owners and individuals with occupational or recreational exposures to these species is paramount to reduce the prevalence of zoonoses associated with rabbit and rodent exposure.

Rationale, Design, and Methodological Aspects of the BUDAPEST-GLOBAL Study (Burden of Atherosclerotic Plaques Study in Twins-Genetic Loci and the Burden of Atherosclerotic Lesions).

PubMed

Maurovich-Horvat, Pál; Tárnoki, Dávid L; Tárnoki, Ádám D; Horváth, Tamás; Jermendy, Ádám L; Kolossváry, Márton; Szilveszter, Bálint; Voros, Viktor; Kovács, Attila; Molnár, Andrea Á; Littvay, Levente; Lamb, Hildo J; Voros, Szilard; Jermendy, György; Merkely, Béla

2015-12-01

The heritability of coronary atherosclerotic plaque burden, coronary geometry, and phenotypes associated with increased cardiometabolic risk are largely unknown. The primary aim of the Burden of Atherosclerotic Plaques Study in Twins-Genetic Loci and the Burden of Atherosclerotic Lesions (BUDAPEST-GLOBAL) study is to evaluate the influence of genetic and environmental factors on the burden of coronary artery disease. By design this is a prospective, single-center, classical twin study. In total, 202 twins (61 monozygotic pairs, 40 dizygotic same-sex pairs) were enrolled from the Hungarian Twin Registry database. All twins underwent non-contrast-enhanced computed tomography (CT) for the detection and quantification of coronary artery calcium and for the measurement of epicardial fat volumes. In addition, a single non-contrast-enhanced image slice was acquired at the level of L3-L4 to assess abdominal fat distribution. Coronary CT angiography was used for the detection and quantification of plaque, stenosis, and overall coronary artery disease burden. For the primary analysis, we will assess the presence and volume of atherosclerotic plaques. Furthermore, the 3-dimensional coronary geometry will be assessed based on the coronary CT angiography datasets. Additional phenotypic analyses will include per-patient epicardial and abdominal fat quantity measurements. Measurements obtained from monozygotic and dizygotic twin pairs will be compared to evaluate the genetic or environmental effects of the given phenotype. The BUDAPEST-GLOBAL study provides a unique framework to shed some light on the genetic and environmental influences of cardiometabolic disorders. © 2015 Wiley Periodicals, Inc.

Anti-arthritic effects of chlorogenic acid in interleukin-1β-induced rabbit chondrocytes and a rabbit osteoarthritis model.

PubMed

Chen, Wei-Ping; Tang, Jing-Li; Bao, Jia-Peng; Hu, Peng-Fei; Shi, Zhong-Li; Wu, Li-Dong

2011-01-01

Cartilage degradation is one of the pathological changes of osteoarthritis (OA), and accumulating evidence suggests an excess of matrix metalloproteinases (MMPs) plays a role in this cartilage breakdown. Here, we investigated the effects of chlorogenic acid (CGA) on the mRNA and protein expression of MMPs in interleukin (IL)-1β-induced rabbit chondrocytes and evaluated the in vivo effects of CGA in experimental OA induced by anterior cruciate ligament transection (ACLT) in rabbits. Using quantitative real-time PCR and ELISA to investigate the expression levels of MMP-1, MMP-3, MMP-13, and tissue inhibitors of metalloproteinase-1(TIMP-1) in IL-1β-induced rabbit chondrocytes, we showed that CGA inhibits the expression of these MMPs while increasing TIMP-1 expression, at both the mRNA and protein levels. In addition, IL-1β-induced activation of nuclear factor kappa B (NF-κB) and the degradation of inhibitor of κB (IκB)-α were suppressed by CGA. In rabbits, CGA decreased cartilage degradation as assessed by morphological and histological analyses. The down-regulation of MMP-1, MMP-3, and MMP-13 expression and up-regulation of TIMP-1 expression were also detected in CGA-treated cartilage compared with vehicle-treated cartilage, confirming these findings in an in vivo model. Taken together, these findings indicate that CGA may be considered as a possible candidate agent in the treatment of OA. Copyright © 2010 Elsevier B.V. All rights reserved.

Island osteoperiosteal flap vitality when isolated from basal bone by silicone interposition: an experimental study in rabbit tibia.

PubMed

Laviv, Amir; Ringeman, Jason; Debecco, Meir; Jensen, Ole T; Casap, Nardy

2014-01-01

This study sought to confirm, through histologic evaluation, the vitality and viability of the island osteoperiosteal flap (i-flap) in a rabbit tibia model. In four rabbits, an osteotomy was performed on the tibial aspect of the right leg. A bone flap was raised, but the periosteal attachment was kept intact. The free-floating i-flap was separated from the rest of the bone by a silicone sheet. The rabbits were to be sacrificed after 1, 2, 4, and 8 weeks and histologic samples examined. All surgeries were accomplished successfully; however, three animals showed fractured tibiae within a few days after surgery and were sacrificed immediately after the fractures were discovered. The fourth rabbit was sacrificed at 4 weeks. Histologic specimens showed vital new bone in the i-flap area and signs of remodeling in the transition zone and the original basal bone. The i-flap remained vital. This suggests potential for use in bone augmentation strategies, particularly for the alveolar split procedure.

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

PubMed

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

2004-05-01

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

Laser-grid trabeculectomy in rabbits: an experimental in-vivo study.

PubMed

Dietlein, Thomas S; Jacobi, Philipp C; Krieglstein, Günter K

2002-02-01

Laser-grid trabeculectomy (TE) is a modification of micro-TE designed to enhance the intra- and postoperative safety of filtering surgery by creating several small oval fistulas (max. diameter <200 microm) beneath a scleral flap without peripheral iridectomy. After dissecting the conjunctiva and a conventional scleral flap, 10 small perforating fistulas were created in five pigmented rabbits in the region of the gray-white border using an erbium:YAG laser with a beveled side-firing 200 microm endoprobe; conventional TE with iridectomy was performed in another five animals. Anterior chamber inspection and IOP measurements of both eyes were conducted on days 1, 4, and 14 after operation. After the last inspection eyes were saved for morphological analysis. Both procedures (laser-grid and conventional TE) led to a reduction of intraocular pressure in the treated eye compared to the control eye. Differences between the outcomes for the two procedures were not statistically significant. Morphology of the eyes treated by laser-grid TE revealed dense scarring of perforations around the center of the ligamenta pectinata and loose tissue refilling of the more peripheral openings. The functional outcome of laser-grid TE in rabbits was similar to that of conventional TE in the short term. Histological examination of microperforations in the area of the trabecular meshwork after 2 weeks indicated that tissue repair was less pronounced than in the more anterior perforations. This morphologic finding may be of importance for non-penetrating glaucoma surgery.

Near-infrared hyperspectral imaging of atherosclerotic tissue phantom

NASA Astrophysics Data System (ADS)

Ishii, K.; Nagao, R.; Kitayabu, A.; Awazu, K.

2013-06-01

A method to identify vulnerable plaques that are likely to cause acute coronary events has been required. The object of this study is identifying vulnerable plaques by hyperspectral imaging in near-infrared range (NIR-HSI) for an angioscopic application. In this study, NIR-HSI of atherosclerotic tissue phantoms was demonstrated under simulated angioscopic conditions. NIR-HSI system was constructed by a NIR super continuum light and a mercury-cadmium-telluride camera. Spectral absorbance values were obtained in the wavelength range from 1150 to 2400 nm at 10 nm intervals. The hyperspectral images were constructed with spectral angle mapper algorithm. As a result, detections of the lipid area in the atherosclerotic tissue phantom under angioscopic observation conditions were achieved especially in the wavelength around 1200 nm, which corresponds to the second overtone of CH stretching vibration mode.

A Critical Role of Platelet Adhesion in the Initiation of Atherosclerotic Lesion Formation

PubMed Central

Massberg, Steffen; Brand, Korbinian; Grüner, Sabine; Page, Sharon; Müller, Elke; Müller, Iris; Bergmeier, Wolfgang; Richter, Thomas; Lorenz, Michael; Konrad, Ildiko; Nieswandt, Bernhard; Gawaz, Meinrad

2002-01-01

The contribution of platelets to the process of atherosclerosis remains unclear. Here, we show in vivo that platelets adhere to the vascular endothelium of the carotid artery in ApoE − / − mice before the development of manifest atherosclerotic lesions. Platelet–endothelial cell interaction involved both platelet glycoprotein (GP)Ibα and GPIIb-IIIa. Platelet adhesion to the endothelium coincides with inflammatory gene expression and preceded atherosclerotic plaque invasion by leukocytes. Prolonged blockade of platelet adhesion in ApoE − / − mice profoundly reduced leukocyte accumulation in the arterial intima and attenuated atherosclerotic lesion formation in the carotid artery bifurcation, the aortic sinus, and the coronary arteries. These findings establish the platelet as a major player in initiation of the atherogenetic process. PMID:12370251

Ventricular tachyarrhythmia-related basal cardiomyopathy in rabbits with vagal stimulation--a novel experimental model for inverted Takotsubo-like cardiomyopathy.

PubMed

Takato, Tetsuya; Ashida, Terunao; Seko, Yoshinori; Fujii, Jun; Kawai, Sachio

2010-07-01

Electrical stimulation of the intact (unsectioned) cervical vagus in rabbits frequently provokes ventricular tachyarrhythmias that are often accompanied by mitral regurgitation. Unique pathological lesions often arise on the mitral valve, papillary muscles, and mitral annulus (mitral complex), the latter two of which become swollen and stiffened. These lesions are reversible in nature. Previous studies have essentially ignored the basal portion except for the mitral annulus. Therefore, the present study examined pathological lesions on the left ventricular basal portion in rabbits. The intact right vagal nerves of 20 anesthetized rabbits were repeatedly electrically stimulated under electrocardiographic monitoring. Colloidal carbon (lml) was injected intravenously immediately after the end of the stimulation and all animals were killed 1 week later. Pathological lesions were identified as carbon deposits visible at gross examination. Ventricular bigeminy was induced after vagal stimulation in 15 (75%) of the 20 rabbits. Pathological lesions were evident on the basal portion in 16 (80%) and on the mitral valve and papillary muscles of 15 (75%) of the 20 rabbits. Ventricular bigeminy was closely associated with the development of the pathological lesions, which were rarely observed on the ventricular apex. Cardiomyopathic lesions involving the basal portion and mitral complex were frequently induced in rabbits by vagal stimulation. These lesions bear a close similarity in distribution and reversibility to inverted Takotsubo cardiomyopathy. Copyright 2010 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

[Experimental study on erysipeloid arthritis in the rabbit after blockage of lymph drainage].

PubMed

Canders, J; Brunner, H; Walter, S; Bernhardt-Huth, D; Huth, F

1979-01-01

The lymph drainage was radically blocked in 29 rabbits. One to three days after the operation Erysipelothrix rhusiopathiae was inoculated subcutaneously into the animals. Some control animals were injected with agents of erysipelas and some only with the sterile solution without additional blockade of the lymph drainage. Light and electron microscopy as well as immuno-histological tests showed that the erysipelas arthritis developing in rabbits closely resembles human rheumatoid arthritis with exsudative-necrotising changes of the synovial membrane, proliferation of synovial cells and subsynovial, perivascular plasmacell, and lymphocyte infiltration. The changes were not intensified by the additional blockade of the lymph drainage, when comparing the side with lymph drainage blockade and the non-operated side. The results may be explained by a marked pathogenetic importance of the erysipelas infection in comparison to the relatively mild, lymphostate dependent alterations as well as by mobilisation of macrophages on the operated side.

Lysophosphatidic acid triggers mast cell-driven atherosclerotic plaque destabilization by increasing vascular inflammation.

PubMed

Bot, Martine; de Jager, Saskia C A; MacAleese, Luke; Lagraauw, H Maxime; van Berkel, Theo J C; Quax, Paul H A; Kuiper, Johan; Heeren, Ron M A; Biessen, Erik A L; Bot, Ilze

2013-05-01

Lysophosphatidic acid (LPA), a bioactive lysophospholipid, accumulates in the atherosclerotic plaque. It has the capacity to activate mast cells, which potentially exacerbates plaque progression. In this study, we thus aimed to investigate whether LPA contributes to plaque destabilization by modulating mast cell function. We here show by an imaging mass spectrometry approach that several LPA species are present in atherosclerotic plaques. Subsequently, we demonstrate that LPA is a potent mast cell activator which, unlike other triggers, favors release of tryptase. Local perivascular administration of LPA to an atherosclerotic carotid artery segment increases the activation status of perivascular mast cells and promotes intraplaque hemorrhage and macrophage recruitment without impacting plaque cell apoptosis. The mast cell stabilizer cromolyn could prevent intraplaque hemorrhage elicited by LPA-mediated mast cell activation. Finally, the involvement of mast cells in these events was further emphasized by the lack of effect of perivascular LPA administration in mast cell deficient animals. We demonstrate that increased accumulation of LPA in plaques induces perivascular mast cell activation and in this way contributes to plaque destabilization in vivo. This study points to local LPA availability as an important factor in atherosclerotic plaque stability.

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. © 2016 The Authors. Published under the terms of the CC BY 4.0 license.

Knee joint transplantation combined with surgical angiogenesis in rabbits – a new experimental model

PubMed Central

Kremer, Thomas; Giusti, Guilherme; Friedrich, Patricia F.; Willems, Wouter; Bishop, Allen T.; Giessler, Goetz A.

2012-01-01

Summary Purpose We have previously described a means to maintain bone allotransplant viability, without long-term immune modulation, replacing allogenic bone vasculature with autogenous vessels. A rabbit model for whole knee joint transplantation was developed and tested using the same methodology, initially as an autotransplant. Materials/Methods Eight New Zealand White rabbit knee joints were elevated on a popliteal vessel pedicle to evaluate limb viability in a non-survival study. Ten additional joints were elevated and replaced orthotopically in a fashion identical to allotransplantation, obviating only microsurgical repairs and immunosuppression. A superficial inferior epigastric facial (SIEF) flap and a saphenous arteriovenous (AV) bundle were introduced into the femur and tibia respectively, generating a neoangiogenic bone circulation. In allogenic transplantation, this step maintains viability after cessation of immunosuppression. Sixteen weeks later, x-rays, microangiography, histology, histomorphometry and biomechanical analysis were performed. Results Limb viability was preserved in the initial 8 animals. Both soft tissue and bone healing occurred in 10 orthotopic transplants. Surgical angiogenesis from the SIEF flap and AV bundle was always present. Bone and joint viability was maintained, with demonstrable new bone formation. Bone strength was less than the opposite side. Arthrosis and joint contractures were frequent. Conclusion We have developed a rabbit knee joint model and evaluation methods suitable for subsequent studies of whole joint allotransplantation. PMID:22113889

Determination of Tropical Forage Preferences Using Two Offering Methods in Rabbits

PubMed Central

Safwat, A. M.; Sarmiento-Franco, L.; Santos-Ricalde, R. H.; Nieves, D.

2014-01-01

Two methods of feed preference trials were compared to evaluate the acceptability of 5 fresh foliages: Leucaena leucocephala, Moringa oleifera, Portulaca oleracea, Guazuma ulmifolia, and Brosimum alicastrum that was included as control. The evaluation included chemical analyses and forage intake by rabbits. The first method was a cafeteria trial; 12 California growing rabbits aged 8 wk, allocated in individual cages, were offered the five forage plants at the same time inside the cage, while in the second trial 60 California growing rabbits aged 8 wk, allocated individually, were randomly distributed into 5 experimental groups (n = 12/group); for each group just one forage species was offered at a time. The testing period for each method lasted for 7 d, preceded by one week of adaptation. The results showed that B. alicastrum and L. lecocephala were the most preferred forages while on the contrary G. ulmifolia was the least preferred one by rabbits. The results also revealed that the CV% value for the 2nd method (16.32%), which the tested forages were presented separately to rabbits, was lower and methodologically more acceptable than such value for the 1st method (34.28%), which all forages were presented together at the same time. It can be concluded that a range of tropical forages were consumed in acceptable quantities by rabbits, suggesting that diets based on such forages with a concentrate supplement could be used successfully for rabbit production. However, growth performance studies are still needed before recommendations could be made on appropriate ration formulations for commercial use. PMID:25049983

Increased condylar growth after experimental relocation of the glenoid fossa.

PubMed

Pirttiniemi, P; Kantomaa, T; Tuominen, M

1993-09-01

Attempts to increase mandibular growth by the stimulation of condylar proliferative activity, either experimentally or with functional appliances in humans, have led to controversial results. The aim of this study was to measure changes in proliferative activity in the mandibular condyle after steady experimental posterior relocation of the glenoid fossa in the rabbit without actively interfering with normal masticatory action. The method differed from most previous experimental procedures, which force the mandible anteriorly to stimulate functional appliance therapy. Twelve 5-day-old rabbits underwent gluing of the interparietal, temporoparietal, and lambdoidal sutures. Three experimental and three control rabbits were injected with tritiated thymidine at 10, 15, 20, and 30 days and were killed after 2 h for histological and autoradiographic examination. The total number of labeled cells in the prechondroblastic layer was higher in the experimental group, the difference being greatest in the 20-day-old rabbits. The highest proliferative activity in the experimental group was found in the area immediately posterior to the articular contact surface. There was a tendency for the cartilage layers to be thicker in the experimental group, especially in the extreme anterior segments of the condyle.

Anti-atherosclerotic and anti-inflammatory actions of sesame oil.

PubMed

Narasimhulu, Chandrakala Aluganti; Selvarajan, Krithika; Litvinov, Dmitry; Parthasarathy, Sampath

2015-01-01

Atherosclerosis, a major form of cardiovascular disease, has now been recognized as a chronic inflammatory disease. Nonpharmacological means of treating chronic diseases have gained attention recently. We previously reported that sesame oil has anti-atherosclerotic properties. In this study, we have determined the mechanisms by which sesame oil might modulate atherosclerosis by identifying genes and inflammatory markers. Low-density lipoprotein receptor knockout (LDLR(-/-)) female mice were fed with either an atherogenic diet or an atherogenic diet reformulated with sesame oil (sesame oil diet). Plasma lipids and atherosclerotic lesions were quantified after 3 months of feeding. Plasma samples were used for cytokine analysis. RNA was extracted from the liver tissue and used for global gene arrays. The sesame oil diet significantly reduced atherosclerotic lesions, plasma cholesterol, triglyceride, and LDL cholesterol levels in LDLR(-/-) mice. Plasma inflammatory cytokines, such as MCP-1, RANTES, IL-1α, IL-6, and CXCL-16, were significantly reduced, demonstrating an anti-inflammatory property of sesame oil. Gene array analysis showed that sesame oil induced many genes, including ABCA1, ABCA2, APOE, LCAT, and CYP7A1, which are involved in cholesterol metabolism and reverse cholesterol transport. In conclusion, our studies suggest that a sesame oil-enriched diet could be an effective nonpharmacological treatment for atherosclerosis by controlling inflammation and regulating lipid metabolism.

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

PubMed

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

2013-03-01

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

Effect of Monocular Deprivation on Rabbit Neural Retinal Cell Densities.

PubMed

Mwachaka, Philip Maseghe; Saidi, Hassan; Odula, Paul Ochieng; Mandela, Pamela Idenya

2015-01-01

To describe the effect of monocular deprivation on densities of neural retinal cells in rabbits. Thirty rabbits, comprised of 18 subject and 12 control animals, were included and monocular deprivation was achieved through unilateral lid suturing in all subject animals. The rabbits were observed for three weeks. At the end of each week, 6 experimental and 3 control animals were euthanized, their retinas was harvested and processed for light microscopy. Photomicrographs of the retina were taken and imported into FIJI software for analysis. Neural retinal cell densities of deprived eyes were reduced along with increasing period of deprivation. The percentage of reductions were 60.9% (P < 0.001), 41.6% (P = 0.003), and 18.9% (P = 0.326) for ganglion, inner nuclear, and outer nuclear cells, respectively. In non-deprived eyes, cell densities in contrast were increased by 116% (P < 0.001), 52% (P < 0.001) and 59.6% (P < 0.001) in ganglion, inner nuclear, and outer nuclear cells, respectively. In this rabbit model, monocular deprivation resulted in activity-dependent changes in cell densities of the neural retina in favour of the non-deprived eye along with reduced cell densities in the deprived eye.

[Immunobiological blood parameters in rabbits after addition to the diet suspensions of chlorella, sodium sulfate, citrate and chromium chloride].

PubMed

Lesyk, Ia V; Fedoruk, R S; Dolaĭchuk, O P

2013-01-01

We studied the content of glycoproteins and their individual carbohydrate components, the phagocyte activity of neutrophils, phagocyte index, phagocyte number lizotsym and bactericidal activity of the serum concentration of circulating immune complexes and middle mass molecules in the blood of rabbits following administration into the diet chlorella suspension, sodium sulfate, chromium citrate and chromium chloride. The studies were conducted on rabbits weighing 3.7-3.9 kg with altered diet from the first day of life to 118 days old. Rabbits were divided into five groups: the control one and four experimental groups. We found that in the blood of rabbits of experimental groups recieved sodium sulphate, chromium chloride and chromium citrate, the content of glycoprotein's and their carbohydrate components was significantly higher during the 118 days of the study compared with the control group. Feeding rabbits with mineral supplements likely reflected the differences compared with the control parameters of nonspecific resistance in the blood for the study period, which was more pronounced in the first two months of life.

An ultrasound-based comparative study on carotid plaques in HIV-positive patients vs. atherosclerotic and arteritis patients: atherosclerotic or inflammatory lesions?

PubMed

Maggi, Paolo; Perilli, Francesco; Lillo, Antonio; Carito, Valentina; Epifani, Giuseppe; Bellacosa, Chiara; Pastore, Giuseppe; Regina, Guido

2007-02-01

We have previously described two cases of HIV-1-positive patients undergoing surgery for stenosis of the internal carotid arteries. Histology revealed an extensive inflammatory infiltration of the vascular wall and no evidence of atheromasic plaque. This unexpected pattern of carotid damage prompted us to perform a more accurate investigation of the characteristics of carotid plaques in a group of HIV-positive patients. The results were compared with those obtained from young patients affected by atherosclerosis of the epi-aortic vessels and patients with arteritis. The patients underwent ultrasonography of the epi-aortic vessels using one of the latest generation power color-Doppler with 7.5 MHz probes. The study population included 61 HIV-positive patients and 47 HIV-negative patients (37 atherosclerotic and 10 with arteritis). Compared with HIV-negative atherosclerotic patients, there were significantly higher proportions of HIV-positive patients with iso-hypoechogenic lesions (81.8 vs. 29%) that were homogeneous both in their parietal and endoluminal portions (96.7 vs. 21.6% and 88.5 vs. 54.0%, respectively), with a smooth or slightly irregular surface (99.0 vs. 56.7%) (P=0.001 for all differences). No statistically significant differences were seen between HIV-positive and arteritis patients. Our study evidenced that the ultrasonographic structure of the epi-aortic lesions in HIV-positive patients substantially differ from those of the plaques in atherosclerotic patients, although they share similar characteristics with patients affected by arteritis. Further investigations are warranted to better define the structure and the mechanism of onset of these lesions.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kabilan, S.; Suffield, S. R.; Recknagle, K. P.

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

A statin-loaded reconstituted high-density lipoprotein nanoparticle inhibits atherosclerotic plaque inflammation

NASA Astrophysics Data System (ADS)

Duivenvoorden, Raphaël; Tang, Jun; Cormode, David P.; Mieszawska, Aneta J.; Izquierdo-Garcia, David; Ozcan, Canturk; Otten, Maarten J.; Zaidi, Neeha; Lobatto, Mark E.; van Rijs, Sarian M.; Priem, Bram; Kuan, Emma L.; Martel, Catherine; Hewing, Bernd; Sager, Hendrik; Nahrendorf, Matthias; Randolph, Gwendalyn J.; Stroes, Erik S. G.; Fuster, Valentin; Fisher, Edward A.; Fayad, Zahi A.; Mulder, Willem J. M.

2014-01-01

Inflammation is a key feature of atherosclerosis and a target for therapy. Statins have potent anti-inflammatory properties but these cannot be fully exploited with oral statin therapy due to low systemic bioavailability. Here we present an injectable reconstituted high-density lipoprotein (rHDL) nanoparticle carrier vehicle that delivers statins to atherosclerotic plaques. We demonstrate the anti-inflammatory effect of statin-rHDL in vitro and show that this effect is mediated through the inhibition of the mevalonate pathway. We also apply statin-rHDL nanoparticles in vivo in an apolipoprotein E-knockout mouse model of atherosclerosis and show that they accumulate in atherosclerotic lesions in which they directly affect plaque macrophages. Finally, we demonstrate that a 3-month low-dose statin-rHDL treatment regimen inhibits plaque inflammation progression, while a 1-week high-dose regimen markedly decreases inflammation in advanced atherosclerotic plaques. Statin-rHDL represents a novel potent atherosclerosis nanotherapy that directly affects plaque inflammation.

The effects of magnesium sulphate and EDTA in the hypercholesterolaemic rabbit.

PubMed

Evans, D A; Tariq, M; Sujata, B; McCann, G; Sobki, S

2001-12-01

Numerous clinical reports suggest the beneficial effects of chelation therapy for the treatment of atherosclerosis. However, the results of these studies are inconclusive and controversial. The purpose of this present study was to examine the prophylactic and therapeutic effects of chelation liquid (CHL) in experimental atherosclerosis. Twenty New Zealand white rabbits were fed a 1% cholesterol-supplemented diet for 45 days. In the prophylactic phase of the study subcutaneous 300 mg EDTA + 500 mg magnesium sulphate (MgSO4) injections (five rabbits) and isotonic saline (five rabbits) were given to test and control groups, respectively, along with cholesterol rich diet. The CHL treatment ameliorated the rise of serum cholesterol and serum triglyceride concentrations, lowered serum calcium concentrations and reduced the aortic atheroma. In the therapeutic phase of the experiment the cholesterol diet was stopped and the remaining 10 animals were returned to normal diet. Five of these rabbits were given CHL injections and other five animals were given isotonic saline injections for 121 days. Although the level of cholesterol and triglyceride were not significantly different in the two groups, the serum calcium concentration and the percentage of the area of flate aortic specimen occupied by atheroma were significantly lower in the CHL treated rabbits as compared to controls. It is concluded that CHL injections have a definite prophylactic effect on atherogenesis in the cholesterol-fed rabbit, and may have some therapeutic value in the regression phase. Further confirmatory studies are suggested.

Histopathological changes in the liver of rabbits exposed to high nitrate ingestion in drinking water.

PubMed

Sharma, Manoj Kumar; Sharma, Hemlata; Bapna, Neelam

2013-08-01

In India, especially in Rajasthan, people drink water which contains high level of nitrates and the possibility of finding concentrations of up to 500 mg of nitrate ions per litre of water is not unusual. Excessive use of nitrate fertilisers and herbicides results in accumulation of nitrate in plants and methemoglobinaemia in cattle as consequences of nitrate poisoning. The ingested nitrate is converted to nitrite in the digestive system and it is absorbed in blood, thus causing methemoglobinaemia. Methaemoglobinaemia is not restricted to infants alone, but it is prevalent in higher age groups also. Therefore, an experimental study was conducted on 10 rabbits which were between three and a half months to four months of age, which had weights which ranged from 1.310 kg to 1.720 kg. Five groups A, B, C,D and E were formed, with two rabbits in each group. The control Group A was given water orally, which had 45 mg/litres of nitrate. Groups B to E (experimental groups) were administered water orally, which had concentrations of 100mg/litre, 200mg/litre, 400mg/litre and 500mg/litre of nitrate respectively, for 120 days. During experimental period, the differences in general behaviour of rabbits were noted. After this, rabbits were anaesthetised and sacrificed according to guidelines of ICMR and their livers were removed and processed for making paraffin sections,.Hematoxyllin and eosin staining was done for microscopic observations. During experimental period, the animals were found to be lethargic on 75(th) day. Quantity of intake of food and water was not altered in the rabbits which were undergoing experiments in different groups. Rabbits of all groups i.e. A to E showed a continuous increase in heart rate (up to 218/minute in Group E) and respiration rate (up to 84/minute in Group E) respectively. The microscopic study showed mild necrosis of hepatocytes, with infiltration of inflammatory cells in between hepatocytes. In higher groups, the liver showed bridging

Atherosclerotic Plaque in Patients with Zero Calcium Score at Coronary Computed Tomography Angiography

PubMed Central

Gabriel, Fabíola Santos; Gonçalves, Luiz Flávio Galvão; de Melo, Enaldo Vieira; Sousa, Antônio Carlos Sobral; Pinto, Ibraim Masciarelli Francisco; Santana, Sara Melo Macedo; de Matos, Carlos José Oliveira; Souto, Maria Júlia Silveira; Conceição, Flávio Mateus do Sacramento; Oliveira, Joselina Luzia Menezes

2018-01-01

Background In view of the high mortality for cardiovascular diseases, it has become necessary to stratify the main risk factors and to choose the correct diagnostic modality. Studies have demonstrated that a zero calcium score (CS) is characteristic of a low risk for cardiovascular events. However, the prevalence of individuals with coronary atherosclerotic plaques and zero CS is conflicting in the specialized literature. Objective To evaluate the frequency of patients with coronary atherosclerotic plaques, their degree of obstruction and associated factors in patients with zero CS and indication for coronary computed tomography angiography (CCTA). Methods This is a cross-sectional, prospective study with 367 volunteers with zero CS at CCTA in four diagnostic imaging centers in the period from 2011 to 2016. A significance level of 5% and 95% confidence interval were adopted. Results The frequency of atherosclerotic plaque in the coronary arteries in 367 patients with zero CS was 9.3% (34 individuals). In this subgroup, mean age was 52 ± 10 years, 18 (52.9%) were women and 16 (47%) had significant coronary obstructions (> 50%), with involvement of two or more segments in 4 (25%) patients. The frequency of non-obese individuals (90.6% vs 73.9%, p = 0.037) and alcohol drinkers (55.9% vs 34.8%, p = 0.015) was significantly higher in patients with atherosclerotic plaques, with an odds ratio of 3.4 for each of this variable. Conclusions The frequency of atherosclerotic plaque with zero CS was relatively high, indicating that the absence of calcification does not exclude the presence of plaques, many of which obstructive, especially in non-obese subjects and alcohol drinkers. PMID:29723329

Atherosclerotic Plaque in Patients with Zero Calcium Score at Coronary Computed Tomography Angiography.

PubMed

Gabriel, Fabíola Santos; Gonçalves, Luiz Flávio Galvão; Melo, Enaldo Vieira de; Sousa, Antônio Carlos Sobral; Pinto, Ibraim Masciarelli Francisco; Santana, Sara Melo Macedo; Matos, Carlos José Oliveira de; Souto, Maria Júlia Silveira; Conceição, Flávio Mateus do Sacramento; Oliveira, Joselina Luzia Menezes

2018-05-03

In view of the high mortality for cardiovascular diseases, it has become necessary to stratify the main risk factors and to choose the correct diagnostic modality. Studies have demonstrated that a zero calcium score (CS) is characteristic of a low risk for cardiovascular events. However, the prevalence of individuals with coronary atherosclerotic plaques and zero CS is conflicting in the specialized literature. To evaluate the frequency of patients with coronary atherosclerotic plaques, their degree of obstruction and associated factors in patients with zero CS and indication for coronary computed tomography angiography (CCTA). This is a cross-sectional, prospective study with 367 volunteers with zero CS at CCTA in four diagnostic imaging centers in the period from 2011 to 2016. A significance level of 5% and 95% confidence interval were adopted. The frequency of atherosclerotic plaque in the coronary arteries in 367 patients with zero CS was 9.3% (34 individuals). In this subgroup, mean age was 52 ± 10 years, 18 (52.9%) were women and 16 (47%) had significant coronary obstructions (> 50%), with involvement of two or more segments in 4 (25%) patients. The frequency of non-obese individuals (90.6% vs 73.9%, p = 0.037) and alcohol drinkers (55.9% vs 34.8%, p = 0.015) was significantly higher in patients with atherosclerotic plaques, with an odds ratio of 3.4 for each of this variable. The frequency of atherosclerotic plaque with zero CS was relatively high, indicating that the absence of calcification does not exclude the presence of plaques, many of which obstructive, especially in non-obese subjects and alcohol drinkers.

Polymeric nanoparticle PET/MR imaging allows macrophage detection in atherosclerotic plaques

PubMed Central

Majmudar, Maulik D.; Yoo, Jeongsoo; Keliher, Edmund J.; Truelove, Jessica; Iwamoto, Yoshiko; Sena, Brena; Dutta, Partha; Borodovsky, Anna; Fitzgerald, Kevin; Di Carli, Marcelo; Libby, Peter; Anderson, Daniel G.; Swirski, Filip K.; Weissleder, Ralph; Nahrendorf, Matthias

2013-01-01

Rationale Myeloid cell content in atherosclerotic plaques associates with rupture and thrombosis. Thus, imaging of lesional monocyte and macrophages (Mo/Mϕ) could serve as a biomarker of disease progression and therapeutic intervention. Objective To noninvasively assess plaque inflammation with dextran nanoparticle-facilitated hybrid PET/MR imaging. Methods and Results Using clinically approved building blocks, we systematically developed 13nm polymeric nanoparticles consisting of crosslinked short chain dextrans which were modified with desferoxamine for zirconium-89 radiolabeling (89Zr-DNP) and a near infrared fluorochrome (VT680) for microscopic and cellular validation. Flow cytometry of cells isolated from excised aortas showed DNP uptake predominantly in Mo/Mϕ (76.7%) and lower signal originating from other leukocytes such as neutrophils and lymphocytes (11.8% and 0.7%, p<0.05 versus Mo/Mϕ). DNP colocalized with the myeloid cell marker CD11b on immunohistochemistry. PET/MRI revealed high uptake of 89Zr-DNP in the aortic root of ApoE−/− mice (standard uptake value, ApoE−/− mice versus wild type controls, 1.9±0.28 versus 1.3±0.03, p<0.05), corroborated by ex vivo scintillation counting and autoradiography. Therapeutic silencing of the monocyte-recruiting receptor CCR2 with siRNA decreased 89Zr-DNP plaque signal (p<0.05) and inflammatory gene expression (p<0.05). Conclusions Hybrid PET/MR imaging with a 13nm DNP enables noninvasive assessment of inflammation in experimental atherosclerotic plaques and reports on therapeutic efficacy of anti-inflammatory therapy. PMID:23300273

Control of rabbit dura mater optical properties with osmotical liquids

NASA Astrophysics Data System (ADS)

Yao, Lei; Cheng, Haiying; Luo, Qingming; Zhang, Wei; Zeng, Shaoqun; Tuchin, Valery V.

2002-04-01

An experimental study of controlling the optical properties of in vitro and in vivo rabbit dura mater with administration of osmotical agents, 40% glucose solution and glycerol, using video camera and spectrometer was presented. The preliminary results of experimental study of influence of osmotical liquids (glucose solutions, glycerol) on transmittance (in vitro) and reflectance (in vivo) spectra of rabbit dura mater were reported. The significant decreasing of the reflectance and increasing of the transmittance of dura mater under action of osmotical solutions were demonstrated. Experiments showed that administration of osmolytes to dura mater allowed for effective and temporary control of its optical characteristics, which made dura mater more transparent, increased the ability of light penetrating the tissue, and consequently improved the optical imaging depth. It is a significant study, which can improve penetration of optical imaging of cerebral function and acquire more information of the deep brain tissue.

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

pediatric TBI patients.36,37 The albumin solution used in this rabbit study was a 5% human albumin (Albminar) in an isotonic solution ( normal saline ... reconstituted easily at the point of injury and injected . Hemostatic properties and bene- fits of FDP or sprayed-dried plasma have been demonstrated...rabbit albumin solution appro- priate for intravenous injection is not commercially available. Rabbit albumin is sold by chemical companies as

Mortality in rabbits transported for slaughter.

PubMed

Voslarova, Eva; Vecerek, Vladimir; Bedanova, Iveta; Vecerkova, Lenka

2018-06-01

During transport rabbits may be exposed to various stressors which can compromise both their welfare and meat quality. Mortality related to the commercial transport of rabbits for slaughter was analyzed in the Czech Republic in the period from 2009 to 2016. The overall transport-related mortality of rabbits was 0.19%. Transport distance was found to have an impact on rabbit mortality; significantly (p < .001) greater losses were found in rabbits transported over longer distances. Mortality rates ranged from 0.02% in rabbits transported over distances of less than 50 km to 0.29% in rabbits transported over distances exceeding 400 km. A significantly (p < .001) increased risk was also associated with shipments in which 500 and more rabbits were delivered per batch. No effect of season was found. Our results show that rabbits can be transported within a wide range of temperatures (from -5 to 19.9°C) with no negative impact on mortality in transit. However, journeys carried out at temperatures below -5°C and above 20°C were associated with increased death losses (0.17% and 0.15%, respectively). © 2018 Japanese Society of Animal Science.

Lysophosphatidic acid triggers mast cell-driven atherosclerotic plaque destabilization by increasing vascular inflammation[S

PubMed Central

Bot, Martine; de Jager, Saskia C. A.; MacAleese, Luke; Lagraauw, H. Maxime; van Berkel, Theo J. C.; Quax, Paul H. A.; Kuiper, Johan; Heeren, Ron M. A.; Biessen, Erik A. L.; Bot, Ilze

2013-01-01

Lysophosphatidic acid (LPA), a bioactive lysophospholipid, accumulates in the atherosclerotic plaque. It has the capacity to activate mast cells, which potentially exacerbates plaque progression. In this study, we thus aimed to investigate whether LPA contributes to plaque destabilization by modulating mast cell function. We here show by an imaging mass spectrometry approach that several LPA species are present in atherosclerotic plaques. Subsequently, we demonstrate that LPA is a potent mast cell activator which, unlike other triggers, favors release of tryptase. Local perivascular administration of LPA to an atherosclerotic carotid artery segment increases the activation status of perivascular mast cells and promotes intraplaque hemorrhage and macrophage recruitment without impacting plaque cell apoptosis. The mast cell stabilizer cromolyn could prevent intraplaque hemorrhage elicited by LPA-mediated mast cell activation. Finally, the involvement of mast cells in these events was further emphasized by the lack of effect of perivascular LPA administration in mast cell deficient animals. We demonstrate that increased accumulation of LPA in plaques induces perivascular mast cell activation and in this way contributes to plaque destabilization in vivo. This study points to local LPA availability as an important factor in atherosclerotic plaque stability. PMID:23396975

Molecular magnetic resonance imaging of atherosclerotic vessel wall disease.

PubMed

Nörenberg, Dominik; Ebersberger, Hans U; Diederichs, Gerd; Hamm, Bernd; Botnar, René M; Makowski, Marcus R

2016-03-01

Molecular imaging aims to improve the identification and characterization of pathological processes in vivo by visualizing the underlying biological mechanisms. Molecular imaging techniques are increasingly used to assess vascular inflammation, remodeling, cell migration, angioneogenesis and apoptosis. In cardiovascular diseases, molecular magnetic resonance imaging (MRI) offers new insights into the in vivo biology of pathological vessel wall processes of the coronary and carotid arteries and the aorta. This includes detection of early vascular changes preceding plaque development, visualization of unstable plaques and assessment of response to therapy. The current review focuses on recent developments in the field of molecular MRI to characterise different stages of atherosclerotic vessel wall disease. A variety of molecular MR-probes have been developed to improve the non-invasive detection and characterization of atherosclerotic plaques. Specifically targeted molecular probes allow for the visualization of key biological steps in the cascade leading to the development of arterial vessel wall lesions. Early detection of processes which lead to the development of atherosclerosis and the identification of vulnerable atherosclerotic plaques may enable the early assessment of response to therapy, improve therapy planning, foster the prevention of cardiovascular events and may open the door for the development of patient-specific treatment strategies. Targeted MR-probes allow the characterization of atherosclerosis on a molecular level. Molecular MRI can identify in vivo markers for the differentiation of stable and unstable plaques. Visualization of early molecular changes has the potential to improve patient-individualized risk-assessment.

Complement factor C5a induces atherosclerotic plaque disruptions

PubMed Central

Wezel, Anouk; de Vries, Margreet R; Lagraauw, H Maxime; Foks, Amanda C; Kuiper, Johan; Quax, Paul HA; Bot, Ilze

2014-01-01

Complement factor C5a and its receptor C5aR are expressed in vulnerable atherosclerotic plaques; however, a causal relation between C5a and plaque rupture has not been established yet. Accelerated atherosclerosis was induced by placing vein grafts in male apoE−/− mice. After 24 days, when advanced plaques had developed, C5a or PBS was applied locally at the lesion site in a pluronic gel. Three days later mice were killed to examine the acute effect of C5a on late stage atherosclerosis. A significant increase in C5aR in the plaque was detectable in mice treated with C5a. Lesion size and plaque morphology did not differ between treatment groups, but interestingly, local treatment with C5a resulted in a striking increase in the amount of plaque disruptions with concomitant intraplaque haemorrhage. To identify the potential underlying mechanisms, smooth muscle cells and endothelial cells were treated in vitro with C5a. Both cell types revealed a marked increase in apoptosis after stimulation with C5a, which may contribute to lesion instability in vivo. Indeed, apoptosis within the plaque was seen to be significantly increased after C5a treatment. We here demonstrate a causal role for C5a in atherosclerotic plaque disruptions, probably by inducing apoptosis. Therefore, intervention in complement factor C5a signalling may be a promising target in the prevention of acute atherosclerotic complications. PMID:25124749

In Vitro Approach To Identify Key Amino Acids in Low Susceptibility of Rabbit Prion Protein to Misfolding

PubMed Central

Eraña, Hasier; Fernández-Borges, Natalia; Elezgarai, Saioa R.; Harrathi, Chafik; Charco, Jorge M.; Chianini, Francesca; Dagleish, Mark P.; Ortega, Gabriel; Millet, Óscar

2017-01-01

ABSTRACT Prion diseases, or transmissible spongiform encephalopathies (TSEs), are a group of rare progressive neurodegenerative disorders caused by an abnormally folded prion protein (PrPSc). This is capable of transforming the normal cellular prion protein (PrPC) into new infectious PrPSc. Interspecies prion transmissibility studies performed by experimental challenge and the outbreak of bovine spongiform encephalopathy that occurred in the late 1980s and 1990s showed that while some species (sheep, mice, and cats) are readily susceptible to TSEs, others are apparently resistant (rabbits, dogs, and horses) to the same agent. To study the mechanisms of low susceptibility to TSEs of certain species, the mouse-rabbit transmission barrier was used as a model. To identify which specific amino acid residues determine high or low susceptibility to PrPSc propagation, protein misfolding cyclic amplification (PMCA), which mimics PrPC-to-PrPSc conversion with accelerated kinetics, was used. This allowed amino acid substitutions in rabbit PrP and accurate analysis of misfolding propensities. Wild-type rabbit recombinant PrP could not be misfolded into a protease-resistant self-propagating isoform in vitro despite seeding with at least 12 different infectious prions from diverse origins. Therefore, rabbit recombinant PrP mutants were designed to contain every single amino acid substitution that distinguishes rabbit recombinant PrP from mouse recombinant PrP. Key amino acid residue substitutions were identified that make rabbit recombinant PrP susceptible to misfolding, and using these, protease-resistant misfolded recombinant rabbit PrP was generated. Additional studies characterized the mechanisms by which these critical amino acid residue substitutions increased the misfolding susceptibility of rabbit PrP. IMPORTANCE Prion disorders are invariably fatal, untreatable diseases typically associated with long incubation periods and characteristic spongiform changes associated

Ribonucleotide Reductase Inhibitors Reduce Atherosclerosis in a Double-Injury Rabbit Model

PubMed Central

Gallaugher, Laura D; Henry, Jon C; Kearns, Patrick N; Elford, Howard L; Bergdall, Valerie K; Cardounel, Arturo J

2009-01-01

Atheroproliferative disorders such as atherosclerosis are an important health problem and one of the leading causes of morbidity and mortality in the United States. Minimally invasive therapeutic procedures, including angioplasty with stent deployment, are used frequently for obstructive coronary artery disease. However, restenosis, a proliferative vascular response, is a common sequela to this procedure. The current study investigated the effect of inhibiting ribonucleotide reductase (RR), an enzyme necessary for cellular proliferation, in an attempt to ameliorate the proliferative response. Two RR inhibitors, didox and hydroxyurea, were chosen for their potent antiproliferative properties. Studies were carried out by using a double-injury rabbit model, in which endothelial denudation was followed by the administration of a high-fat diet. At 4 wk after initial endothelial denudation, the developing atherosclerotic lesion was subjected to transluminal balloon dilation to simulate clinical intervention with percutaneous transluminal angioplasty. The degree of restenosis and atheroproliferation was assessed at 8 wk. Histologic evaluation of the lesion demonstrated that treatment with didox and hydroxyurea significantly decreased lesion area and lumen loss. These results suggest that RR inhibition may be an effective new tool for the treatment of atheroproliferative disorders. PMID:20034432

Simple Additive Weighting to Diagnose Rabbit Disease

NASA Astrophysics Data System (ADS)

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

2018-02-01

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

Valsartan Promoting Atherosclerotic Plaque Stabilization by Upregulating Renalase: A Potential-Related Gene of Atherosclerosis.

PubMed

Zhou, Mingxue; Ma, Chao; Liu, Weihong; Liu, Hongxu; Wang, Ning; Kang, Qunfu; Li, Ping

2015-09-01

Renalase is a protein that can regulate sympathetic nerve activity by metabolizing catecholamines, while redundant catecholamines are thought to contribute to atherosclerosis (As). Catecholamine release can be facilitated by angiotensin (Ang) II by binding to Ang II type 1 (AT1) receptors. Valsartan, a special AT1 antagonist, can dilate blood vessels and reduce blood pressure, but it remained unclear whether valsartan can promote the stability of atherosclerotic plaque by affecting renalase. This study examined the tissue distribution of renalase in ApoE(-/-) mice fed with a high-fat diet and the effect of valsartan on expression of renalase. ApoE(-/-) mice were fed with a high-fat diet for 13 or 26 weeks. As a control, 10 C57BL mice were fed with a standard chow diet. After 13 weeks on the high-fat diet, the ApoE(-/-) mice were randomized (10 mice/group) and treated with valsartan, simvastatin, or distilled water (control group) for an additional 13 weeks accompanied by a high-fat diet. Knockout of ApoE caused a dramatic increase in expression of renalase in mice adipose tissue. With the disturbance of lipid metabolism induced by a high-fat diet, renalase expression decreased in the liver. Renalase can be expressed in smooth muscle cells and M2 macrophages in atherosclerotic plaque, and its expression gradually decreases in the fibrous cap during the transition from stable to vulnerable atherosclerotic plaque. Valsartan, an AT1 receptor antagonist, promotes the stabilization of atherosclerotic plaque by increasing the levels of renalase in serum and the expression of renalase in the fibrous cap of atherosclerotic plaque. It also reduces triglyceride levels in serum and increases the expression of renalase in the liver. Renalase may be a potential-related gene of lipid metabolism and As, and it may be the possible molecular target of valsartan to help stabilize atherosclerotic plaque. © The Author(s) 2015.

A scanning electron microscopy study of CO2 laser-albumin soldering in the rabbit model.

PubMed

Levanon, Daniel; Katzir, Abraham; Ravid, Avi

2004-12-01

We sought to assess the rabbit as an experimental animal in the investigation of laser skin soldering. We studied, using the scanning electron microscope (SEM), the surface appearances of experimental incisions made on the rabbit back skin and soldered by CO(2) laser. Laser soldering of incisions in various tissues is a modality of wound healing of a very promising clinical value. At present, more component studies on animals directed at paving the way towards clinical protocols are needed. Surgical incisions on rabbits back skin were bonded using either albumin-assisted CO(2) laser soldering (experimental) or thread suturing (reference). The incisions closed were excised 2, 3, 4, and 5 days postoperatively, and skin surfaces were studied in the SEM. Naked eye inspection and SEM analysis showed that full-length sealing of soldered and sutured incisions was discernible as early as day 2. In the SEM, all incisions were found confluently coated by epidermal cells along the former cut streak. Soldering subserved to bond incisions efficiently, with surface smooth and close to normal skin. On the other hand, the surface of sutured incisions appeared convoluted and its aesthetic quality inferior to that of the former. Some of the days two and three soldered incisions suffered dehiscence on excision, which suggests an incomplete regeneration of tensile strength at this early phase of healing. Sutured incisions tolerated excision, very probably due to the microthread still present in the skin tissue rather than because of breaking strength regained during wound healing. Also, hair stumps re-grown on the skin by day 5 postoperative might impair satisfactory microscopy of bonded incisions. CO(2) laser soldering of incisions on the rabbit back skin effected rapid wound sealing and resulted in smooth scars indistinguishable from normal skin. The rabbit is well suited for this kind of studies, provided that excision of experimental cuts takes place not later than 5 days post

Changes in Blood Constituents of Rabbits Subjected to Transportation under Hot, Humid Tropical Conditions.

PubMed

Nakyinsige, K; Sazili, A Q; Aghwan, Z A; Zulkifli, I; Goh, Y M; Fatimah, A B

2013-06-01

Unlike Europe (particularly, Italy and Spain), where a number of studies have been conducted on the stressful effects of transport on rabbit welfare, few studies have been conducted on transportation of rabbits under hot, humid tropical conditions experienced in countries like Malaysia. We studied the effects of transportation in hot humid tropical conditions of Malaysia on physiometabolic changes in New Zealand white rabbits. Eighty experimental animals were divided into two groups of 40 bucks each and transported for either 3 or 1 h. Transportation caused a significant upsurge of aspartate aminotransferase, alanine aminotransferase and creatine kinase activities (p<0.001) though did not significantly affect lactate dehydrogenase (LDH) activity (p = 0.0706). Both transportation periods caused elevation in plasma glucose levels, lactic acidosis and dehydration as evidenced through elevated packed cell volume and plasma protein concentration. It was concluded that regardless of the duration, transport of rabbits under hot humid tropical conditions, resulted in heat distress since the rabbits showed hyperglycemia, hypercalcemia, lactacidemia, lymphocytopenia, dehydration and increase in blood enzyme activities.

Marsh rabbit mortalities tie pythons to the precipitous decline of mammals in the Everglades.

PubMed

McCleery, Robert A; Sovie, Adia; Reed, Robert N; Cunningham, Mark W; Hunter, Margaret E; Hart, Kristen M

2015-04-22

To address the ongoing debate over the impact of invasive species on native terrestrial wildlife, we conducted a large-scale experiment to test the hypothesis that invasive Burmese pythons (Python molurus bivittatus) were a cause of the precipitous decline of mammals in Everglades National Park (ENP). Evidence linking pythons to mammal declines has been indirect and there are reasons to question whether pythons, or any predator, could have caused the precipitous declines seen across a range of mammalian functional groups. Experimentally manipulating marsh rabbits, we found that pythons accounted for 77% of rabbit mortalities within 11 months of their translocation to ENP and that python predation appeared to preclude the persistence of rabbit populations in ENP. On control sites, outside of the park, no rabbits were killed by pythons and 71% of attributable marsh rabbit mortalities were classified as mammal predations. Burmese pythons pose a serious threat to the faunal communities and ecological functioning of the Greater Everglades Ecosystem, which will probably spread as python populations expand their range. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

Marsh rabbit mortalities tie pythons to the precipitous decline of mammals in the Everglades

PubMed Central

McCleery, Robert A.; Sovie, Adia; Reed, Robert N.; Cunningham, Mark W.; Hunter, Margaret E.; Hart, Kristen M.

2015-01-01

To address the ongoing debate over the impact of invasive species on native terrestrial wildlife, we conducted a large-scale experiment to test the hypothesis that invasive Burmese pythons (Python molurus bivittatus) were a cause of the precipitous decline of mammals in Everglades National Park (ENP). Evidence linking pythons to mammal declines has been indirect and there are reasons to question whether pythons, or any predator, could have caused the precipitous declines seen across a range of mammalian functional groups. Experimentally manipulating marsh rabbits, we found that pythons accounted for 77% of rabbit mortalities within 11 months of their translocation to ENP and that python predation appeared to preclude the persistence of rabbit populations in ENP. On control sites, outside of the park, no rabbits were killed by pythons and 71% of attributable marsh rabbit mortalities were classified as mammal predations. Burmese pythons pose a serious threat to the faunal communities and ecological functioning of the Greater Everglades Ecosystem, which will probably spread as python populations expand their range. PMID:25788598

Marsh rabbit mortalities tie pythons to the precipitous decline of mammals in the Everglades

USGS Publications Warehouse

McCleery, Robert A.; Sovie, Adia; Reed, Robert N.; Cunningham, Mark W.; Hunter, Margaret E.; Hart, Kristen M.

2015-01-01

To address the ongoing debate over the impact of invasive species on native terrestrial wildlife, we conducted a large-scale experiment to test the hypothesis that invasive Burmese pythons (Python molurus bivittatus) were a cause of the precipitous decline of mammals in Everglades National Park (ENP). Evidence linking pythons to mammal declines has been indirect and there are reasons to question whether pythons, or any predator, could have caused the precipitous declines seen across a range of mammalian functional groups. Experimentally manipulating marsh rabbits, we found that pythons accounted for 77% of rabbit mortalities within 11 months of their translocation to ENP and that python predation appeared to preclude the persistence of rabbit populations in ENP. On control sites, outside of the park, no rabbits were killed by pythons and 71% of attributable marsh rabbit mortalities were classified as mammal predations. Burmese pythons pose a serious threat to the faunal communities and ecological functioning of the Greater Everglades Ecosystem, which will probably spread as python populations expand their range.

Sclareol exerts anti-osteoarthritic activities in interleukin-1β-induced rabbit chondrocytes and a rabbit osteoarthritis model.

PubMed

Zhong, Ying; Huang, Yi; Santoso, Marcel B; Wu, Li-Dong

2015-01-01

Sclareol is a natural product initially isolated form Salvia sclarea which possesses immune-regulation and anti-inflammatory activities. However, the anti-osteoarthritic properties of sclareol have not been investigated. The present study is aimed at evaluating the potential effects of sclareol in interleukin-1β (IL-1β)-induced rabbit chondrocytes as well as an experimental rabbit knee osteoarthritis model induced by anterior cruciate ligament transection (ACLT). Cultured rabbit chondrocytes were pretreated with 1, 5 and 10 μg/mL sclareol for 1 h and followed by stimulation of IL-1β (10 ng/mL) for 24 h. Gene expression of matrix metalloproteinase-1 (MMP-1), MMP-3, MMP-13, tissue inhibitors of metalloproteinase-1 (TIMP-1), inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 was determined by quantitative real-time polymerase chain reaction (qRT-PCR). MMP-3, TIMP-1, iNOS and COX-2 proteins were measured by Western blotting. Enzyme-linked immunosorbent assay (ELISA) was applied for nitric oxide (NO) and prostaglandin E2 (PGE2) assessment. For the in vivo study, rabbits received six weekly 0.3 mL sclareol (10 μg/mL) intra-articular injections in the knees four weeks after ACLT surgery. Cartilage was harvested for measurement of MMP-1, MMP-3, MMP-13, TIMP-1, iNOS and COX-2 by qRT-PCR, while femoral condyles were used for histological evaluation. The in vitro results we obtained showed that sclareol inhibited the MMPs, iNOS and COX-2 expression on mRNA and protein levels, while increased the TIMP-1 expression. And over-production of NO and PGE2 was also suppressed. For the in vivo study, both qRT-PCR results and histological evaluation confirmed that sclareol ameliorated cartilage degradation. Hence, we speculated that sclareol may be an ideal approach for treating osteoarthritis.

Role of infrasound pressure waves in atherosclerotic plaque rupture: a theoretical approach.

PubMed

Tsatsaris, Athanasios; Koukounaris, Efstathios; Motsakos, Theodoros; Perrea, Despina

2007-01-01

To investigate the role of infrasound aortic pressure waves (IPW) in atherosclerotic plaque rupture. Atherosclerotic plaques have been simulated partly, in two dimensions, as being short or long Conical Intersections (CIS), that is to say elliptic, parabolic or hyperbolic surfaces. Consequently, the course and reflection of the generated aortic pressure wave (infrasound domain-less than 20Hz) has been examined around the simulated plaques. The incidence of IPW on plaque surface results both in reflection and "refraction" of the wave. The IPW course within tissue, seems to be enhanced by high Cu-level presence at these areas according to recent evidence (US2003000388213). The "refracted", derived wave travels through plaque tissue and is eventually accumulated to the foci of the respective CIS-plaque geometry. The foci location within or underneath atheroma declares zones where infrasound energy is mostly absorbed. This process, among other mechanisms may contribute to plaque rupture through the development of local hemorrhage and inflammation in foci areas. In future, detection of foci areas and repair (i.e. via Laser Healing Microtechnique) may attenuate atherosclerotic plaque rupture behavior.

Dietary antioxidants preserve endothelium-dependent vessel relaxation in cholesterol-fed rabbits.

PubMed Central

Keaney, J F; Gaziano, J M; Xu, A; Frei, B; Curran-Celentano, J; Shwaery, G T; Loscalzo, J; Vita, J A

1993-01-01

Recent evidence suggests that dietary therapy with lipid-soluble antioxidants may be beneficial for patients with atherosclerotic vascular disease but the potential mechanism(s) for these observations remain obscure. Abnormalities in endothelium-dependent control of vascular tone develop early in the course of atherosclerosis and may result from oxidative modification of low density lipoproteins. We examined the role of dietary antioxidants in preserving normal endothelial cell vasodilator function in cholesterol-fed rabbits with particular attention to possible effects on serum lipoproteins, low density lipoprotein oxidation, and atherogenesis. Male New Zealand White rabbits were fed diets containing no additive (controls), 1% cholesterol (cholesterol group), or 1% cholesterol chow supplemented with either beta-carotene (0.6 g/kg of chow) or alpha-tocopherol (1000 international units/kg of chow) for a 28-day period. After dietary therapy, thoracic aortae were harvested for assay of vascular function and for pathologic examination and tissue antioxidant levels. Compared to controls, acetylcholine- and A23187-mediated endothelium-dependent relaxations were significantly impaired in vessels from the cholesterol group (P < 0.001), whereas vessels from animals treated with beta-carotene or alpha-tocopherol demonstrated normal endothelium-dependent arterial relaxation. Preservation of endothelial function was associated with vascular incorporation of alpha-tocopherol and beta-carotene but was unrelated to plasma lipoprotein levels, smooth muscle cell function, or the extent of atherosclerosis. Increased low density lipoprotein resistance to ex vivo copper-mediated oxidation was observed only in the alpha-tocopherol group. Our results suggest that dietary antioxidants may benefit patients with atherosclerosis by preserving endothelial vasodilator function through a mechanism related to vascular tissue antioxidant content and not reflected by assay of low density

Large Artery Atherosclerotic Occlusive Disease.

PubMed

Cole, John W

2017-02-01

Extracranial or intracranial large artery atherosclerosis is often identified as a potential etiologic cause for ischemic stroke and transient ischemic attack. Given the high prevalence of large artery atherosclerosis in the general population, determining whether an identified atherosclerotic lesion is truly the cause of a patient's symptomatology can be difficult. In all cases, optimally treating each patient to minimize future stroke risk is paramount. Extracranial or intracranial large artery atherosclerosis can be broadly compartmentalized into four distinct clinical scenarios based upon the individual patient's history, examination, and anatomic imaging findings: asymptomatic and symptomatic extracranial carotid stenosis, intracranial atherosclerosis, and extracranial vertebral artery atherosclerotic disease. This review provides a framework for clinicians evaluating and treating such patients. Intensive medical therapy achieves low rates of stroke and death in asymptomatic carotid stenosis. Evidence indicates that patients with severe symptomatic carotid stenosis should undergo carotid revascularization sooner rather than later and that the risk of stroke or death is lower using carotid endarterectomy than with carotid stenting. Specific to stenting, the risk of stroke or death is greatest among older patients and women. Continuous vascular risk factor optimization via sustained behavioral modifications and intensive medical therapy is the mainstay for stroke prevention in the setting of intracranial and vertebral artery origin atherosclerosis. Lifelong vascular risk factor optimization via sustained behavioral modifications and intensive medical therapy are the key elements to reduce future stroke risk in the setting of large artery atherosclerosis. When considering a revascularization procedure for carotid stenosis, patient demographics, comorbidities, and the periprocedural risks of stroke and death should be carefully considered.

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. Copyright © 2015 The Authors. Published by

Effect of Monocular Deprivation on Rabbit Neural Retinal Cell Densities

PubMed Central

Mwachaka, Philip Maseghe; Saidi, Hassan; Odula, Paul Ochieng; Mandela, Pamela Idenya

2015-01-01

Purpose: To describe the effect of monocular deprivation on densities of neural retinal cells in rabbits. Methods: Thirty rabbits, comprised of 18 subject and 12 control animals, were included and monocular deprivation was achieved through unilateral lid suturing in all subject animals. The rabbits were observed for three weeks. At the end of each week, 6 experimental and 3 control animals were euthanized, their retinas was harvested and processed for light microscopy. Photomicrographs of the retina were taken and imported into FIJI software for analysis. Results: Neural retinal cell densities of deprived eyes were reduced along with increasing period of deprivation. The percentage of reductions were 60.9% (P < 0.001), 41.6% (P = 0.003), and 18.9% (P = 0.326) for ganglion, inner nuclear, and outer nuclear cells, respectively. In non-deprived eyes, cell densities in contrast were increased by 116% (P < 0.001), 52% (P < 0.001) and 59.6% (P < 0.001) in ganglion, inner nuclear, and outer nuclear cells, respectively. Conclusion: In this rabbit model, monocular deprivation resulted in activity-dependent changes in cell densities of the neural retina in favour of the non-deprived eye along with reduced cell densities in the deprived eye. PMID:26425316

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

PubMed

Hayashi, K; Teramoto, N; Akagi, T

2002-10-01

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

Histological comparison of autograft, allograft-DBM, xenograft, and synthetic grafts in a trabecular bone defect: an experimental study in rabbits.

PubMed

Athanasiou, Vasilis T; Papachristou, Dionysios J; Panagopoulos, Andreas; Saridis, Alkis; Scopa, Chrisoula D; Megas, Panagiotis

2010-01-01

Different types of bone-graft substitutes have been developed and are on the market worldwide to eliminate the drawbacks of autogenous grafting. This experimental animal study was undertaken to evaluate the different histological properties of various bone graft substitutes utilized in this hospital. Ninety New Zealand white rabbits were divided into six groups of 15 animals. Under general anesthesia, a 4.5 mm-wide hole was drilled into both the lateral femoral condyles of each rabbit, for a total of 180 condyles for analysis. The bone defects were filled with various grafts, these being 1) autograft, 2) DBM crunch allograft (Grafton), 3) bovine cancellous bone xenograft (Lubboc), 4) calcium phosphate hydroxyapatite substitute (Ceraform), 5) calcium sulfate substitute (Osteoset), and 6) no filling (control). The animals were sacrificed at 1, 3, and 6 months after implantation and tissue samples from the implanted areas were processed for histological evaluation. A histological grading scale was designed to determine the different histological parameters of bone healing. The highest histological grades were achieved with the use of cancellous bone autograft. Bovine xenograft (Lubboc) was the second best in the histological scale grading. The other substitutes (Grafton, Ceraform, Osteoset) had similar scores but were inferior to both allograft and xenograft. Bovine xenograft showed better biological response than the other bone graft substitutes; however, more clinical studies are necessary to determine its overall effectiveness.

Adverse reactions in a population of Sydney pet rabbits vaccinated against rabbit calicivirus.

PubMed

Tung, T; Phalen, D; Toribio, J-Alml

2015-11-01

To determine the general clinical presentation and incidence of adverse reactions to Cylap® RCD vaccinations, of a nature serious enough for veterinary attention, in a Sydney population of pet rabbits. A retrospective survey using hospital databases. Nine veterinary hospitals in Sydney participated in a database search for the number of rabbits vaccinated within a 2-year period. The hospitals involved had an identified interest in rabbit medicine and included general, specialist and teaching hospitals. Details of the rabbit, vaccination event and any possible reaction were collected and analysed. Of 933 events recorded in 705 rabbits, 17 (1.8%) adverse reactions were observed. Of the adverse events, local injection site reactions (alopecia, abrasions and scabbing) were most common. Other reactions, including systemic signs of gastrointestinal tract stasis, lethargy and forelimb lameness, were also documented. Overall, rabbits presented for vaccination were mostly male (57.7%) and desexed (71.3%), with an average age of 28.1 months (median 19.0, range 1.4-149.8 months) and an average weight at first vaccination of 2.12 kg (median 2.08 kg, range 0.18-5.6 kg). A significant association between increasing age and decreased incidence of adverse events was demonstrated (P value, 0.038). The benefits of vaccination against RCV outweigh the risks of an adverse reaction occurring. Data from this study show that adverse reactions occur infrequently, are generally mild and self-resolving, and decrease in incidence with increasing age. These results are similar to previous field research on wild rabbit colonies and reports from government and industry. © 2015 Australian Veterinary Association.

Quantification of carotid atherosclerotic plaque components using feature space analysis and magnetic resonance imaging.

PubMed

Karmonik, Christof; Basto, Pamela; Morrisett, Joel D

2006-01-01

Atherosclerosis is one of the main causes of cardiovascular disease, accounting for more than one third of all deaths in the United States, there is a growing need to develop non-invasive techniques to assess the severity of atherosclerotic plaque burden. Recent research has suggested that not the size of the atherosclerotic plaque but rather its composition is indicative for plaque rupture as the underlying event of stroke and acute coronary syndrome. With its excellent soft-tissue contrast, magnetic resonance imaging (MRI) is a favored modality for examining plaque composition. In an ex-vivo study, aimed to show the feasibility of quantifying the components of carotid atherosclerotic plaques in-vivo, we acquired multi-contrast MRI images of 13 freshly excised endarterectomy tissues with commercially available MRI sequences and a human surface coil. Feature space analysis (FSA) was utilized in four representative tissues to determine the total relative abundance of calcific, lipidic, fibrotic, thrombotic and normal components as well as in consecutive 2 mm sections across the carotid bifurcation in each tissue. Excellent qualitative agreement between the FSA results and the results obtained from histological methods was observed. This study demonstrates the feasibility of combining MRI with FSA to quantify carotid atherosclerotic plaques in-vivo.

Icodextrin reduces adhesion formation following gynecological surgery in rabbits

PubMed Central

Khani, Behnaz; Bahrami, Nahid; Mehrabian, Ferdous; Naderi Naeni, Hormoz

2011-01-01

Background: Adhesion is a common complication of gynecology surgery so different barrier agents and solutions have been used during these operations to separate and protect tissues from adhesion after surgery. Adept is one of these solutions that have been postulated to reduce the chance of adhesion following gynecolgy surgery. Objective: To evaluate the effect of 4% icodextrin in reducing adhesion formation in comparing with sterile water and human amniotic fluid in rabbits. Materials and Methods: In this prospective experimental study 30 white Newzealand female rabbits were selected and randomized in to three treatment groups. The rabbits were anesthetized and an abdominal incison was made, uterine horns were abrated with gauze until bleeding occurred. Before closing the abdomen, the traumatized area was irrigated either by 30cc of sterile water, 30cc of 4% Adept or 30cc of human amniotic fluid. The solutions were labeled only as solutions A (steriel water), B (icodextrin), or C (human amniotic fluid). On the seventh day after surgery, second laparotomy was performed to determine and compare adhesion formation in rabbits. Results: There was significant difference between mean score of adhesions in 4% icodextrin group (2.1±0.70) in comparison to sterile water group (10.4±0.60) and amniotic fluid group (8.7±0.84). But the difference between mean score of adhesions in amniotic fluid group in comparison to sterile water group was not significant (8.7±0.84) versus (10.4±0.60). Conclusion: The use of 4% icodextrin solution was more effective than human amniotic fluid and sterile water in reducing adhesion formation in a gynecological surgery model in rabbits PMID:26396562

[Effects of aspirin on dendritic cells in the inflammatory microenvironment of rabbit buccal VX-2 squamous cell carcinoma].

PubMed

Chen, Zhihong; Huang, Guilin; Zhang, Nini; Yi, Jie; Yao, Li; Zhang, Lin

2016-04-01

To explore the effects of aspirin and inflammation on the maturation and function of dendritic cells (DC) on the supernatant of VX-2 squamous cell carcinoma. The rabbit buccal VX-2 squamous cell carcinoma models with inflammation were established by tumor particle implantation, mechanical trauma, and high sugar diet. The rabbits were divided into three groups. For the experimental group (rabbit buccal VX-2 squamous cell carcinoma with local inflammation), aspirin were given by gavage for three consecutive days. For the control group (rabbit buccal VX-2 squamous cell carcinoma with local inflammation), normal saline was given by gavage for three consecutive days. For the blank group (tumor without inflammation), normal saline was given by gavage for three consecutive days. Each tumor specimens were collected in three days and made into tissue homogenate. The supernatant was collected after centrifugation. Normal rabbit peripheral blood mononuclear cells were separated and co-cultured with different states of supernatant. The expression of DC surface markers CD83, CD86, and human leukocyte antigen-DR (HLA-DR) were detected by flow cytometry. The state of function of DC was tested by mixed lymphocyte reaction. The positive rate of CD83, CD86, and HLA-DR of the experimental and control groups were both lower than that of the blank group (P<0.05). In addition, the ability to stimulate T cell proliferation of the experimental and control groups were weaker than that of the blank group (P<0.05). No significant difference was observed between the experi- and HLADR of DC. The short-term administration of aspirin is not conducive to the phenoty and function of DC in a rabbit mental and control groups (P>0.05). Inflammation may inhibit the function and expression of CD83, CD86, buccal VX-2 squamous cell carcinoma inflammatory environment

Intravitreal memantine retinal toxicity in rabbits.

PubMed

Moreno Páramo, D; Reyna Vielma, S; Rodríguez Reyes, A; Hernández Ayuso, I; Quiroz Mercado, H

2016-02-01

To histologically evaluate whether the intravitreal application of memantine produces retinal toxicity in rabbits. A cross-sectional design, experimental, descriptive study was performed on 16 eyes of 16 New Zealand rabbits of 3 kg, divided in 4 groups of 4 rabbits. A dose of 70 ng/ml of intravitreal memantine was administered in Group A, a dose of 150 ng/ml in Group B, a dose of 400 ng/ml in Group C, and Group D received 1 ml of balanced salt solution. The injected eye of half of each group was enucleated 15 days after the injection, and the rest within 30 days after injection. Following enucleation, each eye was placed in 10% formaldehyde. Histopathological analysis was performed on all enucleated eyes. The animals were treated according to the guidelines of the Association for Research on Vision and Ophthalmology (ARVO). Groups A, B and D did not show any histopathological changes after their enucleation at 15 and 30 days. Group C showed changes in the photoreceptor layer after enucleation at 15 and 30 days. In our study, it was observed that memantine concentrations at 70 ng/ml and 150 ng/ml are safe when administered intravitreally; however, doses of 400 ng/ml produced retinal structural changes. This research should continue to assess its clinical usefulness. Copyright © 2015 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

Mast cells mediate neutrophil recruitment during atherosclerotic plaque progression.

PubMed

Wezel, Anouk; Lagraauw, H Maxime; van der Velden, Daniël; de Jager, Saskia C A; Quax, Paul H A; Kuiper, Johan; Bot, Ilze

2015-08-01

Activated mast cells have been identified in the intima and perivascular tissue of human atherosclerotic plaques. As mast cells have been described to release a number of chemokines that mediate leukocyte fluxes, we propose that activated mast cells may play a pivotal role in leukocyte recruitment during atherosclerotic plaque progression. Systemic IgE-mediated mast cell activation in apoE(-/-)μMT mice resulted in an increase in atherosclerotic lesion size as compared to control mice, and interestingly, the number of neutrophils was highly increased in these lesions. In addition, peritoneal mast cell activation led to a massive neutrophil influx into the peritoneal cavity in C57Bl6 mice, whereas neutrophil numbers in mast cell deficient Kit(W(-sh)/W(-sh)) mice were not affected. Within the newly recruited neutrophil population, increased levels of CXCR2(+) and CXCR4(+) neutrophils were observed after mast cell activation. Indeed, mast cells were seen to contain and release CXCL1 and CXCL12, the ligands for CXCR2 and CXCR4. Intriguingly, peritoneal mast cell activation in combination with anti-CXCR2 receptor antagonist resulted in decreased neutrophil recruitment, thus establishing a prominent role for the CXCL1/CXCR2 axis in mast cell-mediated neutrophil recruitment. Our data suggest that chemokines, and in particular CXCL1, released from activated mast cells induce neutrophil recruitment to the site of inflammation, thereby aggravating the ongoing inflammatory response and thus affecting plaque progression and destabilization. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Effect of ascorbic acid on prevention of hypercholesterolemia induced atherosclerosis.

PubMed

Das, S; Ray, R; Snehlata; Das, N; Srivastava, L M

2006-04-01

The notion that oxidation of lipids and propagation of free radicals may contribute to the pathogenesis of atherosclerosis is supported by a large body of evidence. To circumvent the damage caused by oxygen free radicals, antioxidants are needed which provide the much needed neutralization of free radical by allowing the pairing of electrons. In this study we have investigated the effect of ascorbic acid, a water soluble antioxidant on the development of hypercholesterolemia induced atherosclerosis in rabbits. Rabbits were made hypercholesterolemic and atherosclerotic by feeding 100 mg cholesterol/day. Different doses of ascorbic acid were administered to these rabbits. Low dose of ascorbic acid (0.5 mg/100 g body weight/day) did not have any significant effect on the percent of total area covered by atherosclerotic plaque. However, ascorbic acid when fed at a higher dose (15 mg/100 g body weight/day) was highly effective in reducing the atherogenecity. With this dose the percent of total surface area covered by atherosclerotic plaque was significantly less (p < 0.001). This suggests that use of ascorbic acid may have great promise in the prevention of hypercholesterolemia induced atherosclerosis.

Quantitative evaluation of lipid concentration in atherosclerotic plaque phantom by near-infrared multispectral angioscope at wavelengths around 1200 nm

NASA Astrophysics Data System (ADS)

Matsui, Daichi; Ishii, Katsunori; Awazu, Kunio

2015-07-01

Atherosclerosis is a primary cause of critical ischemic diseases like heart infarction or stroke. A method that can provide detailed information about the stability of atherosclerotic plaques is required. We focused on spectroscopic techniques that could evaluate the chemical composition of lipid in plaques. A novel angioscope using multispectral imaging at wavelengths around 1200 nm for quantitative evaluation of atherosclerotic plaques was developed. The angioscope consists of a halogen lamp, an indium gallium arsenide (InGaAs) camera, 3 optical band pass filters transmitting wavelengths of 1150, 1200, and 1300 nm, an image fiber having 0.7 mm outer diameter, and an irradiation fiber which consists of 7 multimode fibers. Atherosclerotic plaque phantoms with 100, 60, 20 vol.% of lipid were prepared and measured by the multispectral angioscope. The acquired datasets were processed by spectral angle mapper (SAM) method. As a result, simulated plaque areas in atherosclerotic plaque phantoms that could not be detected by an angioscopic visible image could be clearly enhanced. In addition, quantitative evaluation of atherosclerotic plaque phantoms based on the lipid volume fractions was performed up to 20 vol.%. These results show the potential of a multispectral angioscope at wavelengths around 1200 nm for quantitative evaluation of the stability of atherosclerotic plaques.

Anti-atherosclerotic effect of Fermentum Rubrum and Gynostemma pentaphyllum mixture in high-fat emulsion- and vitamin D3-induced atherosclerotic rats.

PubMed

Gou, San-Hu; Liu, Bei-Jun; Han, Xiu-Feng; Wang, Li; Zhong, Chao; Liang, Shan; Liu, Hui; Qiang, Yin; Zhang, Yun; Ni, Jing-Man

2018-05-01

The mixture of Hongqu and gypenosides (HG) is composed of Fermentum Rubrum (Hongqu, in Chinese) and total saponins of Gynostemma pentaphyllum (Thunb.) Makino (Jiaogulan, in Chinese) in a 3.6:1 weight ratio. Both Hongqu and Jiaogulan are considered valuable traditional Chinese medicines (TCMs); they have been commonly used in China for the treatment of hyperlipidemia and related diseases for centuries. The aim of the current study was assess the anti-atherosclerotic effect of HG. Sixty-four Wistar rats were randomly divided into eight groups: normal, model, positive control (simvastatin, 1 mg/kg), Hongqu-treated (72 mg/kg), gypenoside (total saponin)-treated (20 mg/kg), and three doses HG-treated (50, 100, and 200 mg/kg). All of the rats were fed a basal diet. Additionally, the model group rats were intragastrically administered a high-fat emulsion and intraperitoneally injected with vitamin D 3 . The serum lipid profiles, oxidative stress, inflammatory cytokine, and hepatic antioxidant levels were then determined. Furthermore, the liver histopathology and arterial tissue were analyzed, and the expression of hyperlipidemia- and atherosclerosis (AS)-related genes was measured using reverse transcription-polymerase chain reaction. The AS rat model was established after 80 days. Compared to the model group, the HG-treated groups showed an obvious improvement in the serum lipid profiles, oxidative stress, and inflammatory cytokine levels, and showed markedly increased hepatic total antioxidant capacity. Moreover, the expression of genes related to lipid synthesis and inflammation reduced and that of the genes related to lipid oxidation increased in the liver and arterial tissue, which also reflected an improved health condition. the anti-atherosclerotic effects of HG were superior to those of simvastatin, Hongqu, and the gypenosides. Therefore, HG may be a useful anti-atherosclerotic TCM preparation. Copyright © 2017. Published by Elsevier Taiwan LLC.

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

Anti-inflammatory and antioxidant effects of Tualang honey in alkali injury on the eyes of rabbits: experimental animal study.

PubMed

Bashkaran, Karuppannan; Zunaina, Embong; Bakiah, Shaharuddin; Sulaiman, Siti Amrah; Sirajudeen, Kns; Naik, Venkatesh

2011-10-09

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. 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. 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 humour (p = 0.117, p = 0

Setup of a bone aging experimental model in the rabbit comparing changes in cortical and trabecular bone: Morphological and morphometric study in the femur.

PubMed

Pazzaglia, Ugo E; Sibilia, Valeria; Congiu, Terenzio; Pagani, Francesca; Ravanelli, Marco; Zarattini, Guido

2015-07-01

Bone aging was studied in an experimental model (rabbit femur) in three populations aged 0.5, 1.5, and 7.5 years. Cortical bone histology was compared with a data set from a 1.5-month-old population of an earlier published paper. From 0.5-year-old onward, the mean femur length did not increase further. Thereafter, the mean marrow area increased and the cortical area decreased significantly with aging. This was associated with a structural pattern transformation from plexiform to laminar and then Haversian-like type. The distal meta-epiphysis bone trabecular density of the oldest populations also was significantly lower in specific regions of interest (ROI). Percentage sealed primary vascular canals in laminar bone significantly increased with aging without variation of percentage sealed secondary osteons. Remodeling rate reflected by the density of cutting cones did not significantly change among the age populations. These data suggest that laminar bone vascular pattern is more functional in the fast diaphyseal expansion but not much streamlined with the renewal of blood flow during secondary remodeling. Bone aging was characterized by: 1) secondary remodeling subendosteally; 2) increment of sealed primary vascular canals number; 3) increased calcium content of the cortex; 4) cortical and trabecular bone mass loss in specific ROIs. Taken together, the present data may give a morphological and morphometric basis to perform comparative studies on experimental models of osteoporosis in the rabbit. © 2015 Wiley Periodicals, Inc.

Brain anatomy of the 4-day-old European rabbit.

PubMed

Schneider, Nanette Y; Datiche, Frédérique; Coureaud, Gérard

2018-05-01

The European rabbit (Oryctolagus cuniculus) is a widely used model in fundamental, medical and veterinary neurosciences. Besides investigations in adults, rabbit pups are relevant to study perinatal neurodevelopment and early behaviour. To date, the rabbit is also the only species in which a pheromone - the mammary pheromone (MP) - emitted by lactating females and active on neonatal adaptation has been described. The MP is crucial since it contributes directly to nipple localisation and oral seizing in neonates, i.e. to their sucking success. It may also be one of the non-photic cues arising from the mother, which stimulates synchronisation of the circadian system during pre-visual developmental stages. Finally, the MP promotes neonatal odour associative and appetitive conditioning in a remarkably rapid and efficient way. For these different reasons, the rabbit offers a currently unique opportunity to determine pheromonal-induced brain processing supporting adaptation early in life. Therefore, it is of interest to create a reference work of the newborn rabbit pup brain, which may constitute a tool for future multi-disciplinary and multi-approach research in this model, and allow comparisons related to the neuroethological basis of social and feeding behaviour among newborns of various species. Here, in line with existing experimental studies, and based on original observations, we propose a functional anatomical description of brain sections in 4-day-old rabbits with a particular focus on seven brain regions which appear important for neonatal perception of sensory signals emitted by the mother, circadian adaptation to the short and single daily nursing of the mother in the nest, and expression of specific motor actions involved in nipple localisation and milk intake. These brain regions involve olfactory circuits, limbic-related areas important in reward, motivation, learning and memory formation, homeostatic areas engaged in food anticipation, and regions

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

PubMed

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

2012-04-01

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

Large Artery Atherosclerotic Occlusive Disease

PubMed Central

Cole, John W.

2017-01-01

ABSTRACT Purpose of Review: Extracranial or intracranial large artery atherosclerosis is often identified as a potential etiologic cause for ischemic stroke and transient ischemic attack. Given the high prevalence of large artery atherosclerosis in the general population, determining whether an identified atherosclerotic lesion is truly the cause of a patient’s symptomatology can be difficult. In all cases, optimally treating each patient to minimize future stroke risk is paramount. Extracranial or intracranial large artery atherosclerosis can be broadly compartmentalized into four distinct clinical scenarios based upon the individual patient’s history, examination, and anatomic imaging findings: asymptomatic and symptomatic extracranial carotid stenosis, intracranial atherosclerosis, and extracranial vertebral artery atherosclerotic disease. This review provides a framework for clinicians evaluating and treating such patients. Recent Findings: Intensive medical therapy achieves low rates of stroke and death in asymptomatic carotid stenosis. Evidence indicates that patients with severe symptomatic carotid stenosis should undergo carotid revascularization sooner rather than later and that the risk of stroke or death is lower using carotid endarterectomy than with carotid stenting. Specific to stenting, the risk of stroke or death is greatest among older patients and women. Continuous vascular risk factor optimization via sustained behavioral modifications and intensive medical therapy is the mainstay for stroke prevention in the setting of intracranial and vertebral artery origin atherosclerosis. Summary: Lifelong vascular risk factor optimization via sustained behavioral modifications and intensive medical therapy are the key elements to reduce future stroke risk in the setting of large artery atherosclerosis. When considering a revascularization procedure for carotid stenosis, patient demographics, comorbidities, and the periprocedural risks of stroke and

Influence of glucocorticosteroids on the biomechanical properties of in-vivo rabbit cornea.

PubMed

Yu, Ji-guo; Bao, Fang-jun; Joda, Akram; Fu, Xun-an; Zhou, Shi; Wang, Jing; Hu, Xiu-li; Wang, Qin-mei; Elsheikh, Ahmed

2014-01-01

Understanding corneal biomechanical responses during long-term glucocorticosteroids administration is important in clinical practice. The purpose of this study is to investigate the biomechanical influence of fluorometholone 0.1% eye drops on rabbit cornea. Thirty-eight Japanese white rabbits were randomly divided into three groups; a fluorometholone group, a supernatant group and a blank control group. For each rabbit in fluorometholone group, one cornea was treated with fluorometholone 0.1% eye drops four times a day for 8 weeks, while corneas of rabbits in supernatant group were treated in the same frequency with supernatant fraction centrifuged from fluorometholone 0.1% eye drops. The rabbits in the blank control group were not given any treatment. At the end of the 8 week observation period, the rabbits were euthanized and the eyes immediately enucleated and prepared for inflation testing. The experimental pressure-deformation data was used to derive the stress-strain behavior of each eye using an inverse modeling procedure. Comparisons of mechanical stiffness of corneas were conducted among the three groups to determine the influence of fluorometholone. The results showed that corneal stiffness decreased as the fluorometholone administration time prolonged. Comparisons of tangent modulus indicated average stiffness reductions of 34.2% and 33.5% in the fluorometholone group compared to the supernatant and control groups, respectively, at the end of the observation period. The stiffness-reduction effect of fluorometholone on the cornea should be considered in clinical management, especially when administrating it to biomechanically weakened corneas, such as after refractive surgeries and in cases of keratoconus. © 2013 Published by Elsevier Ltd.

T Cell CX3CR1 Mediates Excess Atherosclerotic Inflammation in Renal Impairment

PubMed Central

Dong, Lei; Nordlohne, Johannes; Ge, Shuwang; Hertel, Barbara; Melk, Anette; Rong, Song; Haller, Hermann

2016-01-01

Reduced kidney function increases the risk for atherosclerosis and cardiovascular death. Leukocytes in the arterial wall contribute to atherosclerotic plaque formation. We investigated the role of fractalkine receptor CX3CR1 in atherosclerotic inflammation in renal impairment. Apoe−/− (apolipoprotein E) CX3CR1−/− mice with renal impairment were protected from increased aortic atherosclerotic lesion size and macrophage accumulation. Deficiency of CX3CR1 in bone marrow, only, attenuated atherosclerosis in renal impairment in an independent atherosclerosis model of LDL receptor–deficient (LDLr−/−) mice as well. Analysis of inflammatory leukocytes in atherosclerotic mixed bone-marrow chimeric mice (50% wild-type/50% CX3CR1−/− bone marrow into LDLr−/− mice) showed that CX3CR1 cell intrinsically promoted aortic T cell accumulation much more than CD11b+CD11c+ myeloid cell accumulation and increased IL-17-producing T cell counts. In vitro, fewer TH17 cells were obtained from CX3CR1−/− splenocytes than from wild-type splenocytes after polarization with IL-6, IL-23, and TGFβ. Polarization of TH17 or TREG cells, or stimulation of splenocytes with TGFβ alone, increased T cell CX3CR1 reporter gene expression. Furthermore, TGFβ induced CX3CR1 mRNA expression in wild-type cells in a dose- and time-dependent manner. In atherosclerotic LDLr−/− mice, CX3CR1+/− T cells upregulated CX3CR1 and IL-17A production in renal impairment, whereas CX3CR1−/− T cells did not. Transfer of CX3CR1+/− but not Il17a−/− T cells into LDLr−/−CX3CR1−/− mice increased aortic lesion size and aortic CD11b+CD11c+ myeloid cell accumulation in renal impairment. In summary, T cell CX3CR1 expression can be induced by TGFβ and is instrumental in enhanced atherosclerosis in renal impairment. PMID:26449606

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

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

PubMed

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

2014-01-01

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

Population of Computational Rabbit-Specific Ventricular Action Potential Models for Investigating Sources of Variability in Cellular Repolarisation

PubMed Central

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

2014-01-01

Variability is observed at all levels of cardiac electrophysiology. Yet, the underlying causes and importance of this variability are generally unknown, and difficult to investigate with current experimental techniques. The aim of the present study was to generate populations of computational ventricular action potential models that reproduce experimentally observed intercellular variability of repolarisation (represented by action potential duration) and to identify its potential causes. A systematic exploration of the effects of simultaneously varying the magnitude of six transmembrane current conductances (transient outward, rapid and slow delayed rectifier K+, inward rectifying K+, L-type Ca2+, and Na+/K+ pump currents) in two rabbit-specific ventricular action potential models (Shannon et al. and Mahajan et al.) at multiple cycle lengths (400, 600, 1,000 ms) was performed. This was accomplished with distributed computing software specialised for multi-dimensional parameter sweeps and grid execution. An initial population of 15,625 parameter sets was generated for both models at each cycle length. Action potential durations of these populations were compared to experimentally derived ranges for rabbit ventricular myocytes. 1,352 parameter sets for the Shannon model and 779 parameter sets for the Mahajan model yielded action potential duration within the experimental range, demonstrating that a wide array of ionic conductance values can be used to simulate a physiological rabbit ventricular action potential. Furthermore, by using clutter-based dimension reordering, a technique that allows visualisation of multi-dimensional spaces in two dimensions, the interaction of current conductances and their relative importance to the ventricular action potential at different cycle lengths were revealed. Overall, this work represents an important step towards a better understanding of the role that variability in current conductances may play in experimentally observed

Rabbit haemorrhagic disease: advantages of cELISA in assessing immunity in wild rabbits (Oryctolagus cuniculus).

PubMed

Zheng, Tao; Parkes, John P

2011-12-15

Rabbit haemorrhagic disease (RHD) is an acute fatal disease of domestic and wild European rabbits (Oryctolagus cuniculus) caused by RHD virus (RHDV). Accurate assessment of immunity is of great importance for the conservation and control of wild rabbits. We evaluated a competitive ELISA (cELISA) against isotype ELISAs for assessing the protective immunity against the disease by challenging 50 wild-caught rabbits with a lethal dose of RHDV. Death or survival to the challenge was used as a criterion to determine the performance characteristics of the assay for the assessment of immunity in rabbits. At 1:10 dilution, a serum exhibiting ≥ 25% inhibition (1:10(25)) was regarded as the presence of RHDV-specific antibodies. Eleven of 16 (68.8%) rabbits with antibodies at 1:10(25) (<1:40) died of RHD. When the cut-off was moved from 25% to 50% inhibition (1:10(50)) at 1:10 serum dilution, the assay sensitivity, specificity and accuracy for the protective immunity were improved from 84%, 54.2% and 69.4% to 84%, 100% and 91.8%, respectively. We also demonstrated at the epitope amino acid sequence level why the presence of the RHDV-cross reactive benign rabbit calicivirus, which interfered with isotype ELISAs, had little impact on the specificity of the cELISA for the diagnosis of RHDV infection. The presence of RHDV-specific antibody at 1:10(50) by the cELISA is a reliable indicator for the protective immunity. In contrast to isotype ELISAs, the cELISA is a valuable specific tool for monitoring the herd immunity to RHD for the conservation and management of wild rabbits in the field. Copyright © 2011 Elsevier B.V. All rights reserved.

A Salmon Protein Hydrolysate Exerts Lipid-Independent Anti-Atherosclerotic Activity in ApoE-Deficient Mice

PubMed Central

Busnelli, Marco; Bjørndal, Bodil; Holm, Sverre; Brattelid, Trond; Manzini, Stefano; Ganzetti, Giulia S.; Dellera, Federica; Halvorsen, Bente; Aukrust, Pål; Sirtori, Cesare R.; Nordrehaug, Jan E.; Skorve, Jon; Berge, Rolf K.; Chiesa, Giulia

2014-01-01

Fish consumption is considered health beneficial as it decreases cardiovascular disease (CVD)-risk through effects on plasma lipids and inflammation. We investigated a salmon protein hydrolysate (SPH) that is hypothesized to influence lipid metabolism and to have anti-atherosclerotic and anti-inflammatory properties. 24 female apolipoprotein (apo) E−/− mice were divided into two groups and fed a high-fat diet with or without 5% (w/w) SPH for 12 weeks. The atherosclerotic plaque area in aortic sinus and arch, plasma lipid profile, fatty acid composition, hepatic enzyme activities and gene expression were determined. A significantly reduced atherosclerotic plaque area in the aortic arch and aortic sinus was found in the 12 apoE−/− mice fed 5% SPH for 12 weeks compared to the 12 casein-fed control mice. Immunohistochemical characterization of atherosclerotic lesions in aortic sinus displayed no differences in plaque composition between mice fed SPH compared to controls. However, reduced mRNA level of Icam1 in the aortic arch was found. The plasma content of arachidonic acid (C20∶4n-6) and oleic acid (C18∶1n-9) were increased and decreased, respectively. SPH-feeding decreased the plasma concentration of IL-1β, IL-6, TNF-α and GM-CSF, whereas plasma cholesterol and triacylglycerols (TAG) were unchanged, accompanied by unchanged mitochondrial fatty acid oxidation and acyl-CoA:cholesterol acyltransferase (ACAT)-activity. These data show that a 5% (w/w) SPH diet reduces atherosclerosis in apoE−/− mice and attenuate risk factors related to atherosclerotic disorders by acting both at vascular and systemic levels, and not directly related to changes in plasma lipids or fatty acids. PMID:24840793

Systematic characterization of the ionic basis of rabbit cellular electrophysiology using two ventricular models.

PubMed

Romero, Lucía; Carbonell, Beatriz; Trenor, Beatriz; Rodríguez, Blanca; Saiz, Javier; Ferrero, José M

2011-10-01

Several mathematical models of rabbit ventricular action potential (AP) have been proposed to investigate mechanisms of arrhythmias and excitation-contraction coupling. Our study aims at systematically characterizing how ionic current properties modulate the main cellular biomarkers of arrhythmic risk using two widely-used rabbit ventricular models, and comparing simulation results using the two models with experimental data available for rabbit. A sensitivity analysis of AP properties, Ca²⁺ and Na⁺ dynamics, and their rate dependence to variations (±15% and ±30%) in the main transmembrane current conductances and kinetics was performed using the Shannon et al. (2004) and the Mahajan et al. (2008a,b) AP rabbit models. The effects of severe transmembrane current blocks (up to 100%) on steady-state AP and calcium transients, and AP duration (APD) restitution curves were also simulated using both models. Our simulations show that, in both virtual rabbit cardiomyocytes, APD is significantly modified by most repolarization currents, AP triangulation is regulated mostly by the inward rectifier K⁺ current (I(K1)) whereas APD rate adaptation as well as [Na⁺](i) rate dependence is influenced by the Na⁺/K⁺ pump current (I(NaK)). In addition, steady-state [Ca²⁺](i) levels, APD restitution properties and [Ca²⁺](i) rate dependence are strongly dependent on I(NaK), the L-Type Ca²⁺ current (I(CaL)) and the Na⁺/Ca²⁺ exchanger current (I(NaCa)), although the relative role of these currents is markedly model dependent. Furthermore, our results show that simulations using both models agree with many experimentally-reported electrophysiological characteristics. However, our study shows that the Shannon et al. model mimics rabbit electrophysiology more accurately at normal pacing rates, whereas Mahajan et al. model behaves more appropriately at faster rates. Our results reinforce the usefulness of sensitivity analysis for further understanding of cellular

An individual-based model of rabbit viral haemorrhagic disease on European wild rabbits (Oryctolagus cuniculus)

USGS Publications Warehouse

Fa, John E.; Sharples, Colin M.; Bell, Diana J.; DeAngelis, Donald L.

2001-01-01

We developed an individual-based model of Rabbit Viral Hemorrhagic Disease (RVHD) for European wild rabbits (Oryctolagus cuniculus L.), representing up to 1000 rabbits in four hectares. Model output for productivity and recruitment matched published values. The disease was density-dependent and virulence affected outcome. Strains that caused death after several days produced greater overall mortality than strains in which rabbits either died or recovered very quickly. Disease effect also depended on time of year. We also elaborated a larger scale model representing 25 km2 and 100,000+ rabbits, split into a number of grid-squares. This was a more traditional model that did not represent individual rabbits, but employed a system of dynamic equations for each grid-square. Disease spread depended on probability of transmission between neighboring grid-squares. Potential recovery from a major population crash caused by the disease relied on disease virulence and frequency of recurrence. The model's dependence on probability of disease transmission between grid-squares suggests the way that the model represents the spatial distribution of the population affects simulation. Although data on RVHD in Europe are lacking, our models provide a basis for describing the disease in realistic detail and for assessing influence of various social and spatial factors on spread.

Ex-vivo UV autofluorescence imaging and fluorescence spectroscopy of atherosclerotic pathology in human aorta

NASA Astrophysics Data System (ADS)

Lewis, William; Williams, Maura; Franco, Walfre

2017-02-01

The aim of our study was to identify fluorescence excitation-emission pairs correlated with atherosclerotic pathology in ex-vivo human aorta. Wide-field images of atherosclerotic human aorta were captured using UV and visible excitation and emission wavelength pairs of several known fluorophores to investigate correspondence with gross pathologic features. Fluorescence spectroscopy and histology were performed on 21 aortic samples. A matrix of Pearson correlation coefficients were determined for the relationship between relevant histologic features and the intensity of emission for 427 wavelength pairs. A multiple linear regression analysis indicated that elastin (370/460 nm) and tryptophan (290/340 nm) fluorescence predicted 58% of the variance in intima thickness (R-squared = 0.588, F(2,18) = 12.8, p=.0003), and 48% of the variance in media thickness (R-squared = 0.483, F(2,18) = 8.42, p=.002), suggesting that endogenous fluorescence intensity at these wavelengths can be utilized for improved pathologic characterization of atherosclerotic plaques.

Hypoglycaemic effect of a novel insulin buccal formulation on rabbits.

PubMed

Xu, Hui-Bi; Huang, Kai-Xun; Zhu, Yu-Shan; Gao, Qiu-Hua; Wu, Qing-Zhi; Tian, Wei-Qun; Sheng, Xi-Qun; Chen, Ze-Xian; Gao, Zhong-Hong

2002-11-01

Transmucosal delivery is a suitable route for insulin non-injection administration. In this study, the hypoglycaemic effect of INSULIN BUCCAL SPRAY (IBS), a formulation with soybean lecithin and propanediol combined as absorption enhancer for insulin on diabetic rabbits and rats, were investigated. The hypoglycaemic rate was calculated and the pharmacodynamics and pharmacokinetics of the formulation in rabbits were studied. The results show that when the diabetic rabbits were administrated with IBS in dosages of 0.5, 1.5 and 4.5Ukg(-1), the blood glucose level decreased significantly compared with that of the control group and the hypoglycaemic effect lasted over 5h. The blood glucose decreasing rates are 22.4, 48.1 and 53.5%, respectively. The average bioavailability of IBS by buccal delivery versus subcutaneous injection is 29.2%. Meanwhile, the diabetic rats were administrated with IBS in dosages of 1.0, 3.0 and 9.0Ukg(-1), the blood glucose level decreased significantly compared with that of the control group and the hypoglycaemic effect lasted over 4h. The blood glucose decreasing rates are 24.6, 47.5 and 59.6%, respectively. Furthermore, the penetration of fluorescein isothiocyanate (FITC)-labelled insulin through rabbit buccal mucosa was investigated by scanning the distribution of the fluorescent probe in the epithelium using confocal laser scanning microscopy. The results revealed that FITC-insulin can pass through the buccal mucosa promoted by the enhancer and the passage of insulin across the epithelium includes both intracellular and paracellular routes. From the rabbit and rat experimental results showed that IBS is an effective buccal delivery system, which is promising for clinical trial and the future clinical application.

Modeling of Mechanical Stress Exerted by Cholesterol Crystallization on Atherosclerotic Plaques.

PubMed

Luo, Yuemei; Cui, Dongyao; Yu, Xiaojun; Chen, Si; Liu, Xinyu; Tang, Hongying; Wang, Xianghong; Liu, Linbo

2016-01-01

Plaque rupture is the critical cause of cardiovascular thrombosis, but the detailed mechanisms are not fully understood. Recent studies have found abundant cholesterol crystals in ruptured plaques, and it has been proposed that the rapid expansion of cholesterol crystals in a limited space during crystallization may contribute to plaque rupture. To evaluate the effect of cholesterol crystal growth on atherosclerotic plaques, we modeled the expansion of cholesterol crystals during the crystallization process in the necrotic core and estimated the stress on the thin cap with different arrangements of cholesterol crystals. We developed a two-dimensional finite element method model of atherosclerotic plaques containing expanding cholesterol crystals and investigated the effect of the magnitude and distribution of crystallization on the peak circumferential stress born by the cap. Using micro-optical coherence tomography (μOCT), we extracted the cross-sectional geometric information of cholesterol crystals in human atherosclerotic aorta tissue ex vivo and applied the information to the model. The results demonstrate that (1) the peak circumference stress is proportionally dependent on the cholesterol crystal growth; (2) cholesterol crystals at the cap shoulder impose the highest peak circumference stress; and (3) spatial distributions of cholesterol crystals have a significant impact on the peak circumference stress: evenly distributed cholesterol crystals exert less peak circumferential stress on the cap than concentrated crystals.

The Effect of Feed Form on Diet Digestibility and Cecal Parameters in Rabbits

PubMed Central

Alvarenga, Isabella Corsato; Aldrich, Charles Gregory; Kohles, Micah

2017-01-01

Simple Summary In addition to hay or forage in the diet pet rabbits are commonly fed a supplementary food as a muesli (granular mix), pellets, or extruded croquettes. This study aimed to determine if form of this supplementary diet (pelleted vs. extruded) or composition (muesli) had an effect on the diets total tract digestibility and cecal fermentation patterns. Rabbits had slightly higher intake when fed extruded and pelleted diets compared to muesli. Digestibility results were inconsistent between estimation methods. The extruded diet was more digestible than pelleted according to the total collection digestibility method, but according to internal marker acid insoluble ash the pelleted diet was the most digestible. Both the extruded and pelleted diet had similar fermentation patterns, with lower cecal pH and greater proportions of butyrate. Our findings suggest that diet composition, rather than form, may have a greater impact on nutrient utilization by rabbits. Abstract Fifteen New Zealand rabbits were randomly assigned to one of 3 dietary treatment groups of 5 animals each and fed pelleted, extruded, or muesli diets in a completely randomized design experiment. Rabbits were placed in individual cages with ad libitum access to water and food for 45 days acclimation followed by 30 days experimental period. Feed intake of rabbits fed pelleted and extruded diets was greater (p < 0.05) than rabbits fed the muesli diet (125.6 and 130.4 vs. 91.9 g/d), but weight change and feed efficiency were not affected by treatment. Diet digestibility among the treatments was inconsistent when comparing results obtained from total fecal collection and AIA (please define) as an internal marker. Rabbits fed extruded and pelleted diets had lower (p < 0.05) cecal pH (6.42 and 6.38 vs. 7.02, respectively), and higher (p < 0.05) production of SCFA (18.5 and 19.0 vs. 11.7 mM, respectively) than those fed muesli. The fermentation products from rabbits fed pelleted and extruded diets had

Chondromalacia induced by patellar subluxation: morphological and morphometrical aspects in rabbits.

PubMed

Sant'Anna, M M S; Apfel, M I R

2002-01-01

The purpose of this study was to describe morphologically and quantify the changes of the articular cartilage in chondromalacia, concerning both the chondrocytes and extracellular matrix. Eight rabbits were submitted daily to patellar subluxation, causing chondromalacia after two weeks. The knee fragments obtained were processed by the standard methods. These experimental conditions caused degenerative alterations of the articular cartilage, varying from a slight decrease of proteoglycans, to fibrillations, clefts, and horizontal splitting. The results showed a significantly increase number of chondrocytes (p < 0,000139), although smaller in size (p < 0,000109). The immobilization for 2 weeks and the intermittent passive daily motion afterwards for a period of 2 weeks, was effective to cause patellar chrondomalacia in rabbits.

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

Chronic Inflammatory Diseases and Atherosclerotic Cardiovascular Disease: Innocent Bystanders or Partners in Crime?

PubMed

Hansen, Peter Riis

2018-01-01

Inflammation plays a significant role in atherosclerosis and cardiovascular disease (CVD). Patients with chronic inflammatory diseases are at increased risk of CVD, but it is debated whether this association is causal or dependent on shared risk factors, other exposures, genes, and/or inflammatory pathways. The current review summarizes epidemiological, clinical, and experimental data supporting the role of shared inflammatory mechanisms between atherosclerotic CVD and rheumatoid arthritis, psoriasis, inflammatory bowel disease, and periodontitis, respectively, and provides insights to future prospects in this area of research. Awareness of the role of inflammation in CVD in patients with chronic inflammatory diseases and the potential for anti-inflammatory therapy, e.g., with tumor necrosis factor-α inhibitors, to also reduce atherosclerotic CVD has evolved into guideline- based recommendations. These include regular CVD risk assessment, aggressive treatment of traditional CVD risk factors, and recognition of reduced CVD as an added benefit of strict inflammatory disease control. At present, chronic inflammatory diseases would appear to qualify as partners in crime and not merely innocent bystanders to CVD. However, definite incremental contributions of inflammation versus effects of the complex interplay with other CVD risk factors may never be fully elucidated and for the foreseeable future, inflammation is posed to maintain its current position as both a marker and a maker of CVD, with clinical utility both for identification of patient at risk of CVD and as target for therapy to reduce CVD. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Selective removal of cholesterol ester in atherosclerotic plaque using nanosecond pulsed laser at 5.75 μm

NASA Astrophysics Data System (ADS)

Ishii, K.; Tsukimoto, H.; Hazama, H.; Awazu, K.

2008-02-01

Laser angioplasty, for example XeCl excimer laser angioplasty, has gained more attention in addition to conventional methods of surgical and interventional treatment of atherosclerotic diseases such as bypass operation and balloon dilatation. Low degrees of thermal damage after ablation of atherosclerotic lesions have been achieved by XeCl excimer laser at 308 nm. However, in most cases, laser ablation is not selective and normal arterial wall is also damaged. To avoid complications such as severe dissections or perforation of the arterial wall in an angioplasty, a laser light source with high ablation efficiency but low arterial wall injury is desirable. At atherosclerotic lesions, cholesterol accumulates on the tunica intima by establishing an ester bond with fatty acids such as oleic acid, and thus cholesterol ester is the main component of atherosclerotic plaques. Mid-infrared pulsed laser at 5.75 μm is selectively well absorbed in C=O stretching vibration mode of ester bonds. The purpose of this study is to determine the effectiveness of nanosecond pulsed laser at 5.75 μm irradiation of cholesterol ester in atherosclerotic plaques. In this study, we used a mid-infrared tunable solid-state laser which is operated by difference frequency generation method, with a wavelength of 5.75 μm, a pulse width of 5 nsec and a pulse duration of 10 Hz. It was confirmed that non-invasive interaction to normal thoracic aortas could be induce by the parameters, the wavelength of 5.75 μm, the average power densities of 35 W/cm2 and the irradiation time under 10 sec. This study shows that nanosecond pulsed laser irradiations at 5.75 μm provide an alternative laser light source as an effectively cutting, less traumatic tool for removal of atherosclerotic plaque.

Comparison of the Protective Effects of Individual Components of Particulated trans-Sialidase (PTCTS), PTC and TS, against High Cholesterol Diet-Induced Atherosclerosis in Rabbits.

PubMed

Garavelo, Shérrira M; Higuchi, Maria de Lourdes; Pereira, Jaqueline J; Reis, Marcia M; Kawakami, Joyce T; Ikegami, Renata N; Palomino, Suely A P; Wadt, Nilsa S Y; Agouni, Abdelali

2017-01-01

Previous studies showed the presence of Mycoplasma pneumoniae ( M. pneumoniae ) and membrane-shed microparticles (MPs) in vulnerable atherosclerotic plaques. H&S Science and Biotechnology developed PTCTS, composed by natural particles from medicinal plants (PTC) combined with trans -Sialidase (TS), to combat MPs and Mycoplasma pneumoniae . Our aim was to determine the effects of the different components of PTCTS in a rabbit model of atherosclerosis. Rabbits were fed with high cholesterol diet for 12 weeks and treated during the last 6 weeks with either vehicle, PTC, TS, or PTCTS. Lipid profile and quantification of MPs positive for Mycoplasma pneumoniae and oxidized LDL antigens were carried out. Aortas and organs were then histologically analyzed. PTCTS reduced circulating MPs positive for Mycoplasma pneumoniae and oxidized LDL antigens, reduced the plaque area in the abdominal aorta, and caused positive remodeling of the ascendant aorta. PTC caused positive remodeling and reduced plaque area in the abdominal aorta; however, TS had a lipid lowering effect. PTCTS components combined were more effective against atherosclerosis than individual components. Our data reinforce the infectious theory of atherosclerosis and underscore the potential role of circulating MPs. Therefore, the removal of Mycoplasma -derived MPs could be a new therapeutic approach in the treatment of atherosclerosis.

Isolation and characterization of the progenitor cells from the blastema tissue formed at experimentally-created rabbit ear hole.

PubMed

Baghaban Eslaminejad, Mohamadreza; Bordbar, Sima

2013-02-01

Objective(s) : Throughout evolution, mammalians have increasingly lost their ability to regenerate structures however rabbits are exceptional since they develop a blastema in their ear wound for regeneration purposes. Blastema consists of a group of undifferentiated cells capable of dividing and differentiating into the ear tissue. The objective of the present study is to isolate, culture expand, and characterize blastema progenitor cells in terms of their in vitro differentiation capacity. Five New Zealand white male rabbits were used in the present study. Using a punching apparatus, a 4-mm hole was created in the animal ears. Following 4 days, the blastema ring which was created in the periphery of primary hole in the ears was removed and cultivated. The cells migrated from the blastema were expanded through 3 successive subcultures and characterized in terms of their potential differentiation, growth characteristics, and culture requirements. The primary cultures tended to be morphologically heterogeneous having spindly-shaped fibroblast-like cells as well as flattened cells. Fibroblast-like cells survived and dominated the cultures. These cells tended to have the osteogenic, chondrogenic, and adipogenic differentiation potentials. They were highly colonogenic and maximum proliferation was achieved when the cells were plated at density of 100 cells/cm2 in a medium which contained 10% fetal bovine serum (FBS). Taken together, blastema tissue-derived stem cells from rabbit ear are of mesenchymal stem cell-like population. Studies similar to this will assist scientist better understanding the nature of blastema tissue formed at rabbit ear to regenerate the wound.

Medical therapy is best for atherosclerotic renal artery stenosis: Arguments for.

PubMed

Annigeri, R A

2012-01-01

Atherosclerotic renal artery stenosis (ARAS) is a common condition that causes hypertension and reduction in the glomerular filtration rate and is an independent risk factor for death. Despite high technical success, the clinical benefit of renal artery (RA) angioplasty with stenting in ARAS remains doubtful. The published randomized clinical trials provide no support for the notion that renal angioplasty with stenting significantly improves blood pressure, preserves renal function, or reduces episodes of congestive heart failure in patients with ARAS. RA stenting is associated with procedure-related morbidity and mortality. Agents to block the renin-angiotensin-aldosterone system improve outcome and should be a part of a multifaceted medical regimen in ARAS. Medical therapy effectively controls atherosclerotic renovascular disease at all levels of vasculature and hence is the best therapy for ARAS.

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.

Effect of amiloride and bumetanide on transepithelial ion transport in isolated rabbit cecal and colonic wall.

PubMed

Kosik-Bogacka, Danuta; Młodzik-Danielewicz, Natalia; Banach, Bolesław; Tyrakowski, Tomasz

2005-06-03

The aim of the study was to compare the effects of amiloride and bumetanide on the baseline transepithelial electrical potential difference (PD) and changes in PD during mechanical stimulation (dPD) in isolated cecal and colonic wall of rabbits. The experiments were performed with a modified Ussing chamber system. Isolated tissue specimens were incubated in Ringer's solution, in amiloride and/or bumetanide, or in dimethyl sulfoxide (DMSO). Under control conditions, i.e. when all the experimental fluids were Ringer's solution, the PD and R values of the rabbit cecum and colon were similar, while during mechanical stimulation, dPD of the colon was twice as high as that of the cecum. Addition of amiloride and/or bumetanide to all experimental fluids diminished the electrophysiological parameters of both tissues. DMSO added to all experimental fluids significantly diminished the values of the electrophysiological parameters of the cecum. Addition of amiloride to the stimulation fluid only diminished the PD and dPD values in the colon, whereas addition of bumetanide to the stimulation fluid only diminished the PD and dPD values in the cecum. It was found that the PD and dPD values of the rabbit cecum depend primarily on chloride ion transport, while those of the colon depend on sodium ion transport.

Stenting and medical therapy for atherosclerotic renal-artery stenosis.

PubMed

Cooper, Christopher J; Murphy, Timothy P; Cutlip, Donald E; Jamerson, Kenneth; Henrich, William; Reid, Diane M; Cohen, David J; Matsumoto, Alan H; Steffes, Michael; Jaff, Michael R; Prince, Martin R; Lewis, Eldrin F; Tuttle, Katherine R; Shapiro, Joseph I; Rundback, John H; Massaro, Joseph M; D'Agostino, Ralph B; Dworkin, Lance D

2014-01-02

Atherosclerotic renal-artery stenosis is a common problem in the elderly. Despite two randomized trials that did not show a benefit of renal-artery stenting with respect to kidney function, the usefulness of stenting for the prevention of major adverse renal and cardiovascular events is uncertain. We randomly assigned 947 participants who had atherosclerotic renal-artery stenosis and either systolic hypertension while taking two or more antihypertensive drugs or chronic kidney disease to medical therapy plus renal-artery stenting or medical therapy alone. Participants were followed for the occurrence of adverse cardiovascular and renal events (a composite end point of death from cardiovascular or renal causes, myocardial infarction, stroke, hospitalization for congestive heart failure, progressive renal insufficiency, or the need for renal-replacement therapy). Over a median follow-up period of 43 months (interquartile range, 31 to 55), the rate of the primary composite end point did not differ significantly between participants who underwent stenting in addition to receiving medical therapy and those who received medical therapy alone (35.1% and 35.8%, respectively; hazard ratio with stenting, 0.94; 95% confidence interval [CI], 0.76 to 1.17; P=0.58). There were also no significant differences between the treatment groups in the rates of the individual components of the primary end point or in all-cause mortality. During follow-up, there was a consistent modest difference in systolic blood pressure favoring the stent group (-2.3 mm Hg; 95% CI, -4.4 to -0.2; P=0.03). Renal-artery stenting did not confer a significant benefit with respect to the prevention of clinical events when added to comprehensive, multifactorial medical therapy in people with atherosclerotic renal-artery stenosis and hypertension or chronic kidney disease. (Funded by the National Heart, Lung and Blood Institute and others; ClinicalTrials.gov number, NCT00081731.).

SAP deficiency mitigated atherosclerotic lesions in ApoE(-/-) mice.

PubMed

Zheng, Lingyun; Wu, Teng; Zeng, Cuiling; Li, Xiangli; Li, Xiaoqiang; Wen, Dingwen; Ji, Tianxing; Lan, Tian; Xing, Liying; Li, Jiangchao; He, Xiaodong; Wang, Lijing

2016-01-01

Serum amyloid P conpoent (SAP), a member of the pentraxin family, interact with pathogens and cell debris to promote their removal by macrophages and neutrophils and is co-localized with atherosclerotic plaques in patients. However, the exact mechanism of SAP in atherogenesis is still unclear. We investigated whether SAP influence macrophage recruitment and foam cell formation and ultimately affect atherosclerotic progression. we generated apoE(-/-); SAP(-/-) (DKO) mice and fed them western diet for 4 and 8 weeks to characterize atherosclerosis development. SAP deficiency effectively reduced plaque size both in the aorta (p = 0.0006 for 4 wks; p = 0.0001 for 8 wks) and the aortic root (p = 0.0061 for 4 wks; p = 0.0079 for 8wks) compared with apoE(-/-) mice. Meanwhile, SAP deficiency inhibited oxLDL-induced foam cell formation (p = 0.0004) compared with apoE(-/-) mice and SAP treatment increases oxLDL-induced foam cell formation (p = 0.002) in RAW cells. Besides, SAP deficiency reduced macrophages recruitment (p = 0.035) in vivo and in vitro (p = 0.026). Furthermore, SAP treatment enhanced CD36 (p = 0.007) and FcγRI (p = 0.031) expression induced by oxLDL through upregulating JNK and p38 MAPK phosphorylation whereas specific JNK1/2 inhibitor reduced CD36 (p = 0.0005) and FcγRI (P = 0.0007) expression in RAW cell. SAP deficiency also significantly decreased the expression of M1 and M2 macrophage markers and inflammatory cytokines in oxLDL-induced macrophages. SAP deficiency mitigated foam cell formation and atherosclerotic development in apoE(-/-) mice, due to reduction in macrophages recruitment, polarization and pro-inflammatory cytokines and inhibition the CD36/FcγR-dependent signaling pathway. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Myeloperoxidase-oxidized high density lipoprotein impairs atherosclerotic plaque stability by inhibiting smooth muscle cell migration.

PubMed

Zhou, Boda; Zu, Lingyun; Chen, Yong; Zheng, Xilong; Wang, Yuhui; Pan, Bing; Dong, Min; Zhou, Enchen; Zhao, Mingming; Zhang, Youyi; Zheng, Lemin; Gao, Wei

2017-01-10

High density lipoprotein (HDL) has been proved to be a protective factor for coronary heart disease. Notably, HDL in atherosclerotic plaques can be nitrated (NO 2 -oxHDL) and chlorinated (Cl-oxHDL) by myeloperoxidase (MPO), likely compromising its cardiovascular protective effects. Here we determined the effects of NO 2 -oxHDL and Cl-oxHDL on SMC migration using wound healing and transwell assays, proliferation using MTT and BrdU assays, and apoptosis using Annexin-V assay in vitro, as well as on atherosclerotic plaque stability in vivo using a coratid artery collar implantation mice model. Our results showed that native HDL promoted SMC proliferation and migration, whereas NO 2 -oxHDL and Cl-oxHDL inhibited SMC migration and reduced capacity of stimulating SMC proliferation as well as migration, respectively. OxHDL had no significant influence on SMC apoptosis. In addition, we found that ERK1/2-phosphorylation was significantly lower when SMCs were incubated with NO 2 -oxHDL and Cl-oxHDL. Furthermore, transwell experiments showed that differences between native HDL, NO 2 -oxHDL and Cl-oxHDL was abolished after PD98059 (MAPK kinase inhibitor) treatment. In aortic SMCs from scavenger receptor BI (SR-BI) deficient mice, differences between migration of native HDL, NO 2 -oxHDL and Cl-oxHDL treated SMCs vanished, indicating SR-BI's possible role in HDL-associated SMC migration. Importantly, NO 2 -oxHDL and Cl-oxHDL induced neointima formation and reduced SMC positive staining cells in atherosclerotic plaque, resulting in elevated vulnerable index of atherosclerotic plaque. These findings implicate MPO-catalyzed oxidization of HDL may contribute to atherosclerotic plaque instability by inhibiting SMC proliferation and migration through MAPK-ERK pathway which was dependent on SR-BI.

Safety of medium-chain triglycerides used as an intraocular tamponading agent in an experimental vitrectomy model rabbit.

PubMed

Auriol, Sylvain; Mahieu, Laurence; Brousset, Pierre; Malecaze, François; Mathis, Véronique

2013-01-01

To evaluate safety of medium-chain triglycerides used as a possible intraocular tamponading agent. A 20-gauge pars plana vitrectomy was performed in the right eye of 28 rabbits. An ophthalmologic examination was performed every week until rabbits were killed. At days 7, 30, 60, and 90, rabbits were killed and the treated eyes were examined macroscopically and prepared for histologic examination. Principal outcome was retinal toxicity evaluated by light and electron microscopy, and secondary outcomes were the presence of medium-chain triglyceride emulsification, inflammatory reactions, and the development of cataract. Histologic examination did not reveal any retinal toxicity. Two cases of moderate emulsification were observed, but in these cases, emulsification was caused by the perioperative injection of the agent and did not increase during the postoperative period. We noted 13 cases of inflammatory reaction in vitreous cavity and no case of inflammatory reaction in anterior chamber. Two eyes developed cataract as a result of perioperative trauma to the lens with the vitreous cutter and not secondary to the presence of medium-chain triglycerides in the vitreous cavity. Medium-chain triglycerides did not induce morphologic evidence of retinal toxicity. The results suggest that medium-chain triglycerides could be a promising alternative intraocular tamponading agent for the treatment of retinal detachments.

Imaging of the Fibrous Cap in Atherosclerotic Carotid Plaque

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saba, Luca, E-mail: lucasaba@tiscali.i; Potters, Fons; Lugt, Aad van der

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 parametersmore » 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.« less

Benefits of combinative application of probiotic, enterocin M-producing strain Enterococcus faecium AL41 and Eleutherococcus senticosus in rabbits.

PubMed

Lauková, Andrea; Simonová, Monika Pogány; Chrastinová, Ľubica; Plachá, Iveta; Čobanová, Klaudia; Formelová, Zuzana; Chrenková, Mária; Ondruška, Ľubomír; Strompfová, Viola

2016-03-01

This study presents the effects of the probiotic and enterocin M-producing strain Enterococcus faecium AL41 on microbiota, phagocytic activity (PA), oxidative stress, performance and biochemical parameters when applied individually or in combination with Eleutherococcus senticosus in rabbits. The novelty of the study lies in the use of our non-rabbit-derived strain (AL41 = CCM8558) which produces new enterocin M. Ninety-six post-weaned rabbits (Hyplus breed) aged 5 weeks were divided into three experimental groups, 24 in each: E. senticosus (ES, 30 g/100 kg) in feed, E. faecium AL41 (10(9) CFU/mL marked by rifampicin to differentiate it from other enterococci) in water, and ES + AL. AL41 colonized sufficiently in rabbits to reduce coliforms, staphylococci, pseudomonads and clostridia. Slight decrease in bacteria was also found in the caecum and appendix. Phagocytic activity was significantly increased in the experimental groups compared to the control group (CG) (p < 0.001; p < 0.05). Applications did not evoke oxidative stress. Biochemical parameters in blood and caecal organic acids were slightly influenced. Average daily weight gain was slightly higher in ES and AL + ES. Combinative application of E. faecium with E. senticosus can be beneficial in rabbits. AL41 strain alone and in combination with ES produced reduction in spoilage bacteria; the highest stimulation of PA was in the AL41 + ES group.

A Framework for Local Mechanical Characterization of Atherosclerotic Plaques: Combination of Ultrasound Displacement Imaging and Inverse Finite Element Analysis.

PubMed

Akyildiz, Ali C; Hansen, Hendrik H G; Nieuwstadt, Harm A; Speelman, Lambert; De Korte, Chris L; van der Steen, Antonius F W; Gijsen, Frank J H

2016-04-01

Biomechanical models have the potential to predict plaque rupture. For reliable models, correct material properties of plaque components are a prerequisite. This study presents a new technique, where high resolution ultrasound displacement imaging and inverse finite element (FE) modeling is combined, to estimate material properties of plaque components. Iliac arteries with plaques were excised from 6 atherosclerotic pigs and subjected to an inflation test with pressures ranging from 10 to 120 mmHg. The arteries were imaged with high frequency 40 MHz ultrasound. Deformation maps of the plaques were reconstructed by cross correlation of the ultrasound radiofrequency data. Subsequently, the arteries were perfusion fixed for histology and structural components were identified. The histological data were registered to the ultrasound data to construct FE model of the plaques. Material properties of the arterial wall and the intima of the atherosclerotic plaques were estimated using a grid search method. The computed displacement fields showed good agreement with the measured displacement fields, implying that the FE models were able to capture local inhomogeneities within the plaque. On average, nonlinear stiffening of both the wall and the intima was observed, and the wall of the atheroslcerotic porcine iliac arteries was markedly stiffer than the intima (877 ± 459 vs. 100 ± 68 kPa at 100 mmHg). The large spread in the data further illustrates the wide variation of the material properties. We demonstrated the feasibility of a mixed experimental-numerical framework to determine the material properties of arterial wall and intima of atherosclerotic plaques from intact arteries, and concluded that, due to the observed variation, plaque specific properties are required for accurate stress simulations.

A rabbit ventricular action potential model replicating cardiac dynamics at rapid heart rates.

PubMed

Mahajan, Aman; Shiferaw, Yohannes; Sato, Daisuke; Baher, Ali; Olcese, Riccardo; Xie, Lai-Hua; Yang, Ming-Jim; Chen, Peng-Sheng; Restrepo, Juan G; Karma, Alain; Garfinkel, Alan; Qu, Zhilin; Weiss, James N

2008-01-15

Mathematical modeling of the cardiac action potential has proven to be a powerful tool for illuminating various aspects of cardiac function, including cardiac arrhythmias. However, no currently available detailed action potential model accurately reproduces the dynamics of the cardiac action potential and intracellular calcium (Ca(i)) cycling at rapid heart rates relevant to ventricular tachycardia and fibrillation. The aim of this study was to develop such a model. Using an existing rabbit ventricular action potential model, we modified the L-type calcium (Ca) current (I(Ca,L)) and Ca(i) cycling formulations based on new experimental patch-clamp data obtained in isolated rabbit ventricular myocytes, using the perforated patch configuration at 35-37 degrees C. Incorporating a minimal seven-state Markovian model of I(Ca,L) that reproduced Ca- and voltage-dependent kinetics in combination with our previously published dynamic Ca(i) cycling model, the new model replicates experimentally observed action potential duration and Ca(i) transient alternans at rapid heart rates, and accurately reproduces experimental action potential duration restitution curves obtained by either dynamic or S1S2 pacing.

Association between diabetes and different components of coronary atherosclerotic plaque burden as measured by coronary multidetector computed tomography.

PubMed

Yun, Chun-Ho; Schlett, Christopher L; Rogers, Ian S; Truong, Quynh A; Toepker, Michael; Donnelly, Patrick; Brady, Thomas J; Hoffmann, Udo; Bamberg, Fabian

2009-08-01

The aim of the study was to assess differences in the presence, extent, and composition of coronary atherosclerotic plaque burden as detected by coronary multidetector computed tomography (MDCT) between patients with and without diabetes mellitus. We compared coronary atherosclerotic plaques (any plaque, calcified [CAP], non-calcified [NCAP, and mixed plaque [MCAP

The effect of dietary Digestarom® herbal supplementation on rabbit meat fatty acid profile, lipid oxidation and antioxidant content.

PubMed

Mattioli, S; Dal Bosco, A; Szendrő, Zs; Cullere, M; Gerencsér, Zs; Matics, Zs; Castellini, C; Dalle Zotte, A

2016-11-01

The experiment tested the effect of Digestarom® herbal supplementation on the antioxidant content, lipid oxidation and fatty acid profile of rabbit meat. At kindling, rabbit does and litters were divided into two dietary groups (N=162 kits/dietary group) and fed either a control diet (C) or the C diet supplemented with Digestarom® (D: 300mg/kg). At weaning (35days) four experimental fattening groups (54 rabbits each) were considered: CC, CD, DC and DD. After slaughtering (12weeks of age), Longissimus thoracis et lumborum muscles were dissected from 20 rabbits/group and analyzed. Rabbit meat of DD group was enriched in essential C18:3 n-3 fatty acid and in other long-chain PUFA of n-3 series. Despite meat of DD group displayed the highest peroxidability index, TBARs value was the lowest. Meat antioxidant content followed the rank order: DD>CD>DC>CC. Digestarom® improved fatty acid composition and oxidative status of rabbit meat, particularly when administered from weaning throughout the growing period. Copyright © 2016. Published by Elsevier Ltd.

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

Identification of Mature Atherosclerotic Plaque Proteome Signatures Using Data-Independent Acquisition Mass Spectrometry.

PubMed

Hansmeier, Nicole; Buttigieg, Josef; Kumar, Pankaj; Pelle, Shaneen; Choi, Kyoo Yoon; Kopriva, David; Chao, Tzu-Chiao

2018-01-05

Atherosclerosis is a chronic inflammatory disease with complex pathobiology and one of the most common causes of cardiovascular events. The process is characterized by complex vascular remodeling processes that require the actions of numerous proteins. The composition of atherosclerotic plaque is increasingly recognized as a major factor governing the occurrence of cardiovascular or neurological symptoms. To gain deeper insights into the composition of atherosclerotic plaques, we created quantitative proteome profiles of advanced plaque tissues of six male patients undergoing carotid endarterectomy for stroke prevention. Using a quantitative, data-independent proteome approach, we identified 4181 proteins with an average protein coverage of 45%. An analysis of the quantitative composition of the tissue revealed key players of vascular remodeling processes. Moreover, compared with proximal arterial tissue, 20 proteins in mature plaques were enriched, whereas 52 proteins were found in lower quantities. Among the proteins with increased abundance were prominent extracellular matrix proteins such as biglycan and lumican, whereas cytoskeletal markers for contractile smooth muscle cells (SMCs) were decreased. Taken together, this study provides the most comprehensive quantitative assessment of mature human plaque tissue to date, which indicates a central role of SMCs in the structure of advanced atherosclerotic plaques.

Ex vivo detection of macrophages in atherosclerotic plaques using intravascular ultrasonic-photoacoustic imaging

NASA Astrophysics Data System (ADS)

Quang Bui, Nhat; Hlaing, Kyu Kyu; Lee, Yong Wook; Kang, Hyun Wook; Oh, Junghwan

2017-01-01

Macrophages are excellent imaging targets for detecting atherosclerotic plaques as they are involved in all the developmental stages of atherosclerosis. However, no imaging technique is currently capable of visualizing macrophages inside blood vessel walls. The current study develops an intravascular ultrasonic-photoacoustic (IVUP) imaging system combined with indocyanine green (ICG) as a contrast agent to provide morphological and compositional information about the targeted samples. Both tissue-mimicking vessel phantoms and atherosclerotic plaque-mimicking porcine arterial tissues are used to demonstrate the feasibility of mapping macrophages labeled with ICG by endoscopically applying the proposed hybrid technique. A delay pulse triggering technique is able to sequentially acquire photoacoustic (PA) and ultrasound (US) signals from a single scan without using any external devices. The acquired PA and US signals are used to reconstruct 2D cross-sectional and 3D volumetric images of the entire tissue with the ICG-loaded macrophages injected. Due to high imaging contrast and sensitivity, the IVUP imaging vividly reveals structural information and detects the spatial distribution of the ICG-labeled macrophages inside the samples. ICG-assisted IVUP imaging can be a feasible imaging modality for the endoscopic detection of atherosclerotic plaques.

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

What We Have Learned from the Recent Meta-analyses on Diagnostic Methods for Atherosclerotic Plaque Regression.

PubMed

Biondi-Zoccai, Giuseppe; Mastrangeli, Simona; Romagnoli, Enrico; Peruzzi, Mariangela; Frati, Giacomo; Roever, Leonardo; Giordano, Arturo

2018-01-17

Atherosclerosis has major morbidity and mortality implications globally. While it has often been considered an irreversible degenerative process, recent evidence provides compelling proof that atherosclerosis can be reversed. Plaque regression is however difficult to appraise and quantify, with competing diagnostic methods available. Given the potential of evidence synthesis to provide clinical guidance, we aimed to review recent meta-analyses on diagnostic methods for atherosclerotic plaque regression. We identified 8 meta-analyses published between 2015 and 2017, including 79 studies and 14,442 patients, followed for a median of 12 months. They reported on atherosclerotic plaque regression appraised with carotid duplex ultrasound, coronary computed tomography, carotid magnetic resonance, coronary intravascular ultrasound, and coronary optical coherence tomography. Overall, all meta-analyses showed significant atherosclerotic plaque regression with lipid-lowering therapy, with the most notable effects on echogenicity, lipid-rich necrotic core volume, wall/plaque volume, dense calcium volume, and fibrous cap thickness. Significant interactions were found with concomitant changes in low density lipoprotein cholesterol, high density lipoprotein cholesterol, and C-reactive protein levels, and with ethnicity. Atherosclerotic plaque regression and conversion to a stable phenotype is possible with intensive medical therapy and can be demonstrated in patients using a variety of non-invasive and invasive imaging modalities.

Microstructural and ultrastructural assessment of inferior alveolar nerve damage following nerve lateralization and implant placement: an experimental study in rabbits.

PubMed

Yoshimoto, Marcelo; Watanabe, Il-sei; Martins, Marília T; Salles, Marcos B; Ten Eyck, Gary R; Coelho, Paulo G

2009-01-01

The present study assessed damage to the inferior alveolar nerve (IAN) following nerve lateralization and implant placement surgery through optical and transmission electron microscopy (TEM). IAN lateralization was performed in 16 adult female rabbits (Oryctolagus cuniculus). During the nerve lateralization procedure, one implant was placed through the mandibular canal, and the IAN was replaced in direct contact with the implant. The implant was placed in the right mandible, and the left side was used as a control (no surgical procedure). After 8 weeks, the animals were sacrificed and samples were prepared for optical and TEM analysis of IAN structural damage. Histomorphometric analysis was performed to determine the number and cross-sectional dimensions of nerve fascicles and myelin sheath thickness between experimental and control groups. The different parameters were compared by one-way analysis of variance at the 95% significance level. Alterations in the perineural and endoneural regions of the IAN, with higher degrees of vascularization, were observed in the experimental group. TEM showed that the majority of the myelinated nerve fibers were not affected in the experimental samples. No significant variation in the number of fascicles was observed, significantly larger fascicle height and width were observed in the control group, and significantly thicker myelin sheaths were observed in the experimental samples. IAN lateralization resulted in substantial degrees of tissue disorganization at the microstructural level because of the presence of edema. However, at the ultrastructural level, small amounts of fiber degeneration were observed.

Experimental uveitis can be maintained in rabbits for a period of six weeks after a safe sensitization method.

PubMed

Eperon, S; Balaskas, K; Vaudaux, J; Guex-Crosier, Y

2013-03-01

New treatments against long-lasting uveitis need to be tested. Our aim was to develop a six-week model of uveitis in rabbits. Rabbits were presensitized with an s.c. injection of Mycobacterium tuberculosis H37RA emulsified with TiterMax Gold adjuvant. Uveitis was induced at day 28 and 50, by intravitreal challenges of antigen suspension. Ocular inflammation was assessed till euthanasia at day 71 after s.c. injection of M. tuberculosis H37RA by: (a) the number of inflammatory cells in aqueous humor (AH); (b) the protein concentration in AH; (c) the clinical score (mean of conjunctival hyperaemia, conjunctival chemosis, oedema and secretion); (d) the microscopical score (mean presence of fibrin and synechiae, aqueous cell density and aqueous flare grade, as scored by slit lamp). At the sites of presensitization injection, rabbits presented flat nodules which progressively vanished. The first challenge induced a significant increase in the four parameters (p < 0.05 the Wilcoxon/Kruskal-Wallis test). The AH contained 764 ± 82 cells/µl and 32 ± 0.77 mg protein/ml. During the following days, inflammatory parameters decreased slightly. The second intravitreal challenge increased inflammation (3564 ± 228 cells/µl AH and 31 ± 1 mg protein/ml), which remained at a high level for a longer period of time. We developed a model of long-term uveitis, which could be maintained in rabbits for at least six weeks. Such a model could be used to test the efficacy of either new drugs or various drug delivery systems intended to deliver active agents during a few months.

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

PubMed

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

2004-11-06

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

Effects of iloprost and piracetam in spinal cord ischemia-reperfusion injury in the rabbit.

PubMed

Kalkan, E; Keskin, F; Kaya, B; Esen, H; Tosun, M; Kalkan, S S; Erdi, F; Unlü, A; Avunduk, M C; Cicek, O

2011-01-01

Experimental Study. The aim of this study was to investigate the neuroprotective effects of iloprost and piracetam on spinal cord ischemia/reperfusion (I/R) injury in the rabbit. The Experimental Research Center of Selcuk University, Konya, Turkey. A total of 24 rabbits were divided into four groups of six rabbits each, as follows: group 1 (n = 6) sham, laparotomy only; group 2 (n = 6) I/R; group 3 (n = 6) I/R+iloprost; and group 4 (n = 6) I/R+piracetam. I/R was established in groups 2, 3 and 4. Subsequently, they were followed up neurologically for 24 h until the rabbits were killed; biochemical and histopathological examinations of samples from the spinal cord were carried out. Neurological examination results were significantly better in the iloprost and piracetam groups compared with the I/R group (P < 0.05). Neuroprotection was achieved with iloprost and piracetam by suppressing malondialdehyde (P < 0.05), increasing glutathione peroxidase activity (P < 0.05) and decreasing the xanthine oxidase level. In histopathological assessment, iloprost and piracetam groups were statistically different from the I/R group in terms of the number of apoptotic neurons in gray matter and white matter, as well as in terms of degenerated neurons and glial cells (P < 0.05). No statistical difference was determined between the four groups in the number of degenerated glial cells (P > 0.05). This study has shown that iloprost and piracetam have neuroprotective effects in I/R injury both neurologically and histopathologically because of inhibition of lipid peroxidation.

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

A survey of fur mites in domestic rabbits.

PubMed

Flatt, R E; Wiemers, J

1976-10-01

A survey of six commercial rabbit colonies was conducted to determine the prevalence of the mite Cheyletiella parasitvorax. This mite was present in all six colonies, and 43.2% of 220 rabbits examined were infested. Listrophorus gibbus, reported only once previously in domestic rabbits in the United States, was found in four of the six colonies, and in 7.3% of the 220 rabbits examined. Non-parasitic mites were found in 3.2% of the samples. Over 50% of the rabbits examined had inapparent mite infestations.

Near-infrared autofluorescence induced by intraplaque hemorrhage and heme degradation as marker for high-risk atherosclerotic plaques.

PubMed

Htun, Nay Min; Chen, Yung Chih; Lim, Bock; Schiller, Tara; Maghzal, Ghassan J; Huang, Alex L; Elgass, Kirstin D; Rivera, Jennifer; Schneider, Hans G; Wood, Bayden R; Stocker, Roland; Peter, Karlheinz

2017-07-13

Atherosclerosis is a major cause of mortality and morbidity, which is mainly driven by complications such as myocardial infarction and stroke. These complications are caused by thrombotic arterial occlusion localized at the site of high-risk atherosclerotic plaques, of which early detection and therapeutic stabilization are urgently needed. Here we show that near-infrared autofluorescence is associated with the presence of intraplaque hemorrhage and heme degradation products, particularly bilirubin by using our recently created mouse model, which uniquely reflects plaque instability as seen in humans, and human carotid endarterectomy samples. Fluorescence emission computed tomography detecting near-infrared autofluorescence allows in vivo monitoring of intraplaque hemorrhage, establishing a preclinical technology to assess and monitor plaque instability and thereby test potential plaque-stabilizing drugs. We suggest that near-infrared autofluorescence imaging is a novel technology that allows identification of atherosclerotic plaques with intraplaque hemorrhage and ultimately holds promise for detection of high-risk plaques in patients.Atherosclerosis diagnosis relies primarily on imaging and early detection of high-risk atherosclerotic plaques is important for risk stratification of patients and stabilization therapies. Here Htun et al. demonstrate that vulnerable atherosclerotic plaques generate near-infrared autofluorescence that can be detected via emission computed tomography.

Bioeffect of lipohemia rabbits irradiated in oral mucosa with 650-nm diode-laser-accompanied oxygen inspiration and clinical application

NASA Astrophysics Data System (ADS)

Yang, Fu-Shou; Tang, Jin-Xian; Liu, Cheng; Yang, Xi-Cheng; Pang, Hi-Xiu

1998-11-01

The study on irradiating in oral mucosa of rabbits with 650 nm diode laser and clinical application has been reported in this paper. The result of animal experiment showed: the obvious decrease of cholesterin and triglyceride has been found among those highly lipohemia rabbits in the experiments of 650nm diode laser irradiating accompanying with oxygen, as well as the parameters of hemorheology obviously being improved, as compared with highly lipohemia rabbits un-irradiating, the statistical analysis showing P < 0.01. In the meantime, the observation of histopathology shows, the lipide decreasing in aorta wall, intramyocardinal membranous layer,and renal interstitial in the group of rabbits which are irradiated with laser and accompanying with oxygen inspiration, and even the perfectly recovered tissue in some rabbits has been seen. This experimental result is significantly for clinical application. The results of clinic application showed, that the patients employed this method which treatment cerebral infarction, lipohemia, the total effective ratio achieved 91.7 percent, perfect effect 30.6 percent.

Diabetes modifies the role of prostanoids and potassium channels which regulate the hypereactivity of the rabbit renal artery to BNP.

PubMed

Centeno, José M; Miranda-Gómez, Luis; López-Morales, Mikahela A; Jover-Mengual, Teresa; Burguete, María C; Marrachelli, Vannina G; Castelló-Ruiz, María; Aliena-Valero, Alicia; Alborch, Enrique; Miranda, Francisco J

2018-05-01

Diabetic nephropathy is associated with increased risk of cardiovascular disease. B-type natriuretic peptide (BNP) plays an important role in cardiovascular pathophysiology and therapeutics. The aim of the present study was to investigate the influence of experimental diabetes on the mechanisms that regulate the relaxant response of the rabbit renal artery to BNP. Arterial relaxations to BNP were enhanced in diabetic rabbits. Indomethacin enhanced BNP-induced relaxation in control rabbits but showed no effect in diabetic rabbits. BNP-induced release of thromboxane A 2 or prostacyclin was not different in both groups of animals. Iberiotoxin had no effect on relaxations to BNP in both groups of animals. Charybdotoxin displaced to the right the concentration-response curve to BNP in both group of animals, and inhibited BNP-induced relaxation only in diabetic rabbits. Glibenclamide did not modify the BNP-induced relaxations in control rabbits, but inhibited it in diabetic rabbits. These results suggest that diabetes induces hypereactivity of the rabbit renal artery to BNP by mechanisms that at least include (1) a reduced vasoconstrictor influence of arachidonic acid metabolites via cyclooxygenase 2, which is not related with changes in thromboxane A 2 and prostacyclin release from the arterial wall and (2) a selectively increased modulatory activity of K ATP and endothelial IK Ca channels.

Proteoglycan 4 regulates macrophage function without altering atherosclerotic lesion formation in a murine bone marrow-specific deletion model.

PubMed

Nahon, Joya E; Hoekstra, Menno; Havik, Stefan R; Van Santbrink, Peter J; Dallinga-Thie, Geesje M; Kuivenhoven, Jan-Albert; Geerling, Janine J; Van Eck, Miranda

2018-05-05

Proteoglycan 4 (Prg4) has a high structural similarity with the established atherosclerosis-modulating proteoglycan versican, but its role in atherogenesis is still unknown. Therefore, the impact of Prg4 deficiency on macrophage function in vitro and atherosclerosis susceptibility in vivo was investigated. The presence and localization of Prg4 was studied in atherosclerotic lesions. Furthermore, the effect of Prg4 deficiency on macrophage foam cell formation, cholesterol efflux and lipopolysaccharide (LPS) response was determined. Finally, susceptibility for atherosclerotic lesion formation was investigated in bone marrow-specific Prg4 knockout (KO) mice. Prg4 mRNA expression was induced 91-fold (p<0.001) in murine initial atherosclerotic lesions and Prg4 protein co-localized with human lesional macrophages. Murine Prg4 KO macrophages showed increased foam cell formation (+2.1-fold, p<0.01). In parallel, the expression of the cholesterol efflux genes ATP-binding cassette transporter A1 and scavenger receptor type B1 was lower (-35%, p<0.05;-40%, p<0.05) in Prg4 KO macrophages. This translated into an impaired cholesterol efflux to high-density lipoprotein (-13%, p<0.001) and apolipoprotein A1 (-8%, p<0.05). Furthermore, Prg4 KO macrophages showed an impaired LPS-induced rise in TNFα secretion as compared to wild-type controls (-31%, p<0.001), indicating a reduced inflammatory response. Combined, these pro- and anti-atherogenic effects did not translate into a significant difference in atherosclerotic lesion formation upon bone marrow-specific deletion of Prg4 in low-density lipoprotein receptor KO mice. Prg4 is present in macrophages in both murine and human atherosclerotic lesions and critically influences macrophage function, but deletion of Prg4 in bone marrow-derived cells does not affect atherosclerotic lesion development. Copyright © 2018 Elsevier B.V. All rights reserved.

Potential benefits of eicosapentaenoic acid on atherosclerotic plaques.

PubMed

Nelson, J R; Wani, O; May, H T; Budoff, M

2017-04-01

Residual cardiovascular (CV) risk remains in some patients despite optimized statin therapy and may necessitate add-on therapy to reduce this risk. Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, lowers plasma triglyceride levels without raising low-density lipoprotein cholesterol levels and has potential beneficial effects on atherosclerotic plaques. Animal studies have shown that EPA reduces levels of pro-inflammatory cytokines and chemokines. In clinical trials utilizing a wide spectrum of plaque imaging modalities, EPA has shown beneficial effects on plaque characteristics. Studies of patients with coronary artery disease receiving statin therapy suggest that EPA may decrease plaque vulnerability and prevent plaque progression. EPA also decreased pentraxin-3 and macrophage accumulation. A large, randomized, Japanese study reported that EPA plus a statin resulted in a 19% relative reduction in major coronary events at 5years versus a statin alone in patients with hypercholesterolemia (P=0.011). Icosapent ethyl, a high-purity prescription form of EPA ethyl ester, has been shown to reduce triglyceride levels and markers of atherosclerotic inflammation. Results of an ongoing CV outcomes study will further define the potential clinical benefits of icosapent ethyl in reducing CV risk in high-risk patients receiving statin therapy. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Atorvastatin Upregulates the Expression of miR-126 in Apolipoprotein E-knockout Mice with Carotid Atherosclerotic Plaque.

PubMed

Pan, Xudong; Hou, Rongyao; Ma, Aijun; Wang, Ting; Wu, Mei; Zhu, Xiaoyan; Yang, Shaonan; Xiao, Xing

2017-01-01

Carotid atherosclerosis (AS) is a chronic inflammatory disease of the carotid arterial wall, which is very important in terms of the occurrence of cerebral vascular accidents. Studies have demonstrated that microRNAs (miRNAs) and their target genes are involved in the formation of atherosclerosis and that atorvastatin might reduce atherosclerotic plaques by regulating the expression of miRNAs. However, the related mechanism is not yet known. In this study, we first investigated the effects of atorvastatin on miR-126 and its target gene, i.e., vascular cell adhesion molecule-1 (VCAM-1) in apolipoprotein E-knockout (ApoE-/-) mice with carotid atherosclerotic plaque in vivo. We compared the expressions of miR-126 and VCAM-1 between the control, atherosclerotic model and atorvastatin treatment groups of ApoE-/- mice using RT-PCR and Western blot. We found the miR-126 expression was significantly down-regulated, and the VCAM-1 expression was significantly up-regulated in the atherosclerotic model group, which accelerated the progression of atherosclerosis in the ApoE-/- mice. These results following atorvastatin treatment indicated that miR-126 expression was significantly up-regulated, VCAM-1 expression was significantly down-regulated and atherosclerotic lesions were reduced. The present results might explain the mechanism by which miR-126 is involved in the formation of atherosclerosis in vivo. Our study first indicated that atorvastatin might exert its anti-inflammatory effects in atherosclerosis by regulating the expressions of miR-126 and VCAM-1 in vivo.

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

PubMed Central

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

2016-01-01

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

Increased virulence of Rabbit Haemorrhagic Disease Virus associated with genetic resistance in wild Australian rabbits (Oryctolagus cuniculus)

PubMed Central

Elsworth, Peter; Cooke, Brian D.; Kovaliski, John; Sinclair, Ronald; Holmes, Edward C.; Strive, Tanja

2015-01-01

The release of myxoma virus (MYXV) and Rabbit Haemorrhagic Disease Virus (RHDV) in Australia with the aim of controlling overabundant rabbits has provided a unique opportunity to study the initial spread and establishment of emerging pathogens, as well as their co-evolution with their mammalian hosts. In contrast to MYXV, which attenuated shortly after its introduction, rapid attenuation of RHDV has not been observed. By studying the change in virulence of recent field isolates at a single field site we show, for the first time, that RHDV virulence has increased through time, likely because of selection to overcome developing genetic resistance in Australian wild rabbits. High virulence also appears to be favoured as rabbit carcasses, rather than diseased animals, are the likely source of mechanical insect transmission. These findings not only help elucidate the co-evolutionary interaction between rabbits and RHDV, but reveal some of the key factors shaping virulence evolution. PMID:25146599

Hypocholesterolemic effects of low calorie structured lipids on rats and rabbits fed on normal and atherogenic diet.

PubMed

Kanjilal, Sanjit; Kaki, Shiva Shanker; Rao, Bhamidipati V S K; Sugasini, Dhavamani; Rao, Yalagala Poornachandra; Prasad, Rachapudi B N; Lokesh, Belur R

2013-01-01

The hypocholesterolemic effects of two low calorie structured lipids (SL1 and SL2) containing essential fatty acids, prepared by lipase catalysed interesterification of ethyl behenate respectively with sunflower and soybean oils were studied in rats and rabbits. The feeding experiment conducted on rats as well as rabbits, fed on normal and atherogenic diet containing 10% of SL1 and SL2 (experimental) and sunflower oil (control) indicated no adverse effects on growth and food intake. However, the structured lipids beneficially lowered serum and liver lipids, particularly cholesterol, LDL cholesterol, triglycerides and also maintains the essential fatty acid status in serum and liver. The lipid deposition observed in the arteries of rabbits fed on atherogenic diets was significantly reduced when structured lipids were included in the diet. These observations coincided with reduced levels of serum cholesterol particularly LDL cholesterol observed in experimental groups. Therefore the structured lipids, designed to have low calorific value also beneficially lower serum lipids and lipid deposition in animals fed on atherogenic diets. Copyright © 2012 Elsevier Ltd. All rights reserved.

A case of low success of blind vaccination campaigns against myxomatosis and rabbit haemorrhagic disease on survival of adult European wild rabbits.

PubMed

Rouco, Carlos; Moreno, Sacramento; Santoro, Simone

2016-10-01

Vaccination campaigns against myxomatosis and rabbit haemorrhagic disease (RHD) are commonly used in translocation programs conducted for the purpose of recovering wild European rabbit populations in Iberian Mediterranean ecosystems. In most cases rabbits are vaccinated 'blind' (i.e. without assessing their prior immunological status) for economic and logistic reasons. However, there is conflicting evidence on the effectiveness of such an approach. We tested whether blind vaccination against myxomatosis and rabbit haemorrhagic disease improved rabbit survival in a rabbit translocation program where wild rabbits were kept in semi-natural conditions in three enclosures. We conducted nine capture sessions over two years (2008-2010) and used the information collected to compare the survival of vaccinated (n=511) versus unvaccinated (n=161) adult wild rabbits using capture-mark-recapture analysis. Average monthly survival was no different for vaccinated versus unvaccinated individuals, both in the period between release and first capture (short-term) and after the first capture onward (long-term). Rabbit survival was lower in the short term than in the long term regardless of whether rabbits were vaccinated or not. Lower survival in the short-term could be due to the stress induced by the translocation process itself (e.g. handling stress). However, we did not find any overall effect of vaccination on survival which could be explained by two non-exclusive reasons. First, interference of the vaccine with the natural antibodies in the donor population. Due to donor populations have high density of rabbits with, likely, high prevalence of antibodies as a result of previous natural exposure to these diseases. Second, the lack of severe outbreaks during the study period. Based on our findings we argue that blind vaccination of adult rabbits in translocation programs may be often mostly ineffective and unnecessarily costly. In particular, since outbreaks are hard to predict

[Influence of high-voltage electric burn on the microcirculation of heart in rabbit].

PubMed

Zhang, Qing-fu; Zhou, Hui-min; Wang, Che-jiang; Shao, Hong-bo

2012-06-01

To study the influence of high-voltage electric burn on the microcirculation of heart in rabbit. One-hundred and twenty New Zealand rabbits of clean grade were divided into control group (C) and electric burn group (EB) according to the random number table, with 60 rabbits in each group. Rabbits in EB group were subjected to high-voltage electric burn (the electrical current flow into the left foreleg at the lateral side of proximal end and out from the corresponding site of the right hind leg) with voltage regulator and experimental transformer. Rabbits in C group were sham injured with the same devices without electrification. At 15 minutes before injury, and 5 minutes, 1, 2, 4, 8 hour (s) post injury (PIM or PIH), ten rabbits in each group were chosen to examine the cardiac apex microcirculation hemoperfusion (CAMH) with laser Doppler hemoperfusion image instrument. The morphologic changes of microvessels of left ventricular wall tissues of 2 rabbits from each of the 10 rabbits collected at above-mentioned time points were observed with light microscope and transmission electron microscope. Auricular vein blood of rabbit was harvested at above-mentioned time points for the determination of aspartate amino transferase (AST), lactate dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBDH), creatine kinase (CK), and creatine kinase isozyme MB (CK-MB) by full-automatic biochemical analyzer. Data were processed with two-factor analysis of variance and LSD test. (1) The differences between C group and EB group in detection results were statistically significant, with F values from 425.991 to 3046.834, P values all below 0.01. Only the data within EB group were comparable. (2) At PIM 5, the CAMH value of rabbits in EB group was (1.96 ± 0.09) V, which was lower than that at 15 minutes before injury [(4.34 ± 0.35) V, P < 0.01]. The CAMH value of rabbits in EB group was increased at PIH 1 [(3.43 ± 0.30) V], and then it showed a tendency of decrease. (3) Bleeding and

Gene Targeting in Rabbits: Single-Step Generation of Knock-out Rabbits by Microinjection of CRISPR/Cas9 Plasmids.

PubMed

Kawano, Yoshihiro; Honda, Arata

2017-01-01

The development of genome editing technology has allowed gene disruptions to be achieved in various animal species and has been beneficial to many mammals. Gene disruption using pluripotent stem cells is difficult to achieve in rabbits, but thanks to advances in genome editing technology, a number of gene disruptions have been conducted. This paper describes a simple and easy method for carrying out gene disruptions in rabbits using CRISPR/Cas9 in which the gene to be disrupted is marked, the presence or absence of off-target candidates is checked, and a plasmid allowing simultaneous expression of Cas9 and sgRNA is constructed. Next, the cleaving activity of candidate sequences is investigated, and assessments are carried out to determine whether the target sequences can be cut. Female rabbits subjected to superovulation treatment are mated with male rabbits and fertilized eggs are collected, and then pronuclear injection of plasmid DNA is performed. The next day, the two-cell stage embryos are transplanted into pseudopregnant rabbits, and offspring are born within approximately 29-30 days. The genomic DNA of the offspring is then examined to check what types of genetic modifications have occurred. With the advent of CRISPR/Cas9, the accessibility of gene disruptions in rabbits has improved remarkably. This paper summarizes specifically how to carry out gene disruptions in rabbits.

NICOTINE METABOLISM IN PREGNANT AND NON-PREGNANT RABBITS

PubMed Central

Tutka, Piotr; Dempsey, Delia A.; Jacob, Peyton; Benowitz, Neal L.; Kroetz, Deanna L.

2010-01-01

Smoking remains a major public health concern during pregnancy and is associated with numerous adverse effects. Recently the clearance of nicotine (NIC) and cotinine (COT) was shown to be substantially increased in pregnant women compared to non-pregnant controls. The present study investigated the usefulness of the rabbit for studying the molecular basis for the observed changes in NIC and COT disposition during pregnancy. NIC was largely metabolized to COT in rabbit liver microsomes (approximately 50% of total metabolism) with significant amounts of nicotine-N’-oxide and nornicotine also being detected. The conversion of NIC to COT was also detected in rabbit placental and fetal liver microsomes albeit at only a fraction of the rate in adult rabbit liver microsomes. The major products of COT metabolism in rabbit liver microsomes were 5’-hydroxycotinine, cotinine-N’-oxide and norcotinine. Differences between human and rabbit liver were most apparent for COT, with the major human metabolite 3’-hydroxycotinine, being formed at only low levels in rabbit liver microsomes. Pregnancy had no effect on the metabolism of NIC or on the expression of CYP2A6 immunoreactive proteins in rabbit liver microsomes. These studies provide a complete quantitative assessment of NIC metabolism in rabbit liver microsomes and suggest that the rabbit may not be an appropriate animal model to study the effects of pregnancy on NIC and COT metabolism. However, a molecular understanding of these effects is essential for prediction of the pharmacological and toxicological consequences of smoking during pregnancy. PMID:18686186

EphA2 knockdown attenuates atherosclerotic lesion development in ApoE(-/-) mice.

PubMed

Jiang, Hong; Li, Xinyun; Zhang, Xiaoli; Liu, Yan; Huang, Shanying; Wang, Xiaowei

2014-01-01

The inflammatory response of vascular endothelial cells plays important roles in the initiation and progression of atherosclerotic lesions. EphA2 receptor activation promotes the endothelial cell inflammatory response, and its expression is increased in the endothelial cell layer of atherosclerotic plaques. However, the association between EphA2 and atherosclerosis has not been determined. Eight-week-old male ApoE(-/-) mice were systemically infected with adenoassociated virus serotype 9 carrying a small hairpin RNA specifically targeting the EphA2 gene to knock down EphA2 expression in aortic endothelial cells. These mice were then fed a high-cholesterol diet for 12 weeks. Blood was collected for the measurement of plasma lipids. The aortas were harvested to evaluate the atherosclerotic lesion size, macrophage components, and expression of proinflammatory genes using Oil Red O staining, immunofluorescence staining, and molecular biology analysis. The lesions formed in the entire aorta and aortic sinus of the ApoE(-/-) mice with EphA2 knockdown were significantly smaller than those in the control mice (10.7%±3.1% versus 25.1%±4.2%; 0.51±0.02mm(2) versus 0.85±0.03mm(2); n=10; P<.05). Furthermore, the lesions in the ApoE(-/-) mice with EphA2 knockdown displayed reduced inflammation compared with the control mice, as reflected by the decreased macrophage infiltration (8.2%±2.9% versus 22.7%±4%; n=10; P<.05); decreased nuclear factor-κβ activation; and diminished expression of vascular cell adhesion molecule-1, E-selectin, and monocyte chemotactic protein-1 (all P<.05). Our data demonstrate that the EphA2 receptor silencing attenuates the extent and inflammation of atherosclerotic lesions in ApoE(-/-) mice. Thus, EphA2 knockdown in endothelial cells represents a novel therapeutic strategy for patients with atherosclerosis. Copyright © 2014 Elsevier Inc. All rights reserved.

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. Copyright © 2011 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.

Physiological and biochemical changes after boldenone injection in adult rabbits.

PubMed

Tousson, Ehab; El-Moghazy, Mostafa; Massoud, Ahmed; El-Atrash, Afaf; Sweef, Osama; Akel, Amani

2016-01-01

Boldenone (BOL) is an androgenic steroid that improves the growth and food conversion in food-producing animals. In most countries worldwide, this anabolic steroid is forbidden for human uses and meat production as it was developed for veterinary use. Recently, BOL is used by bodybuilders in both off season and pre-contest, where it is well known for increasing vascularity while preparing for a bodybuilding contest. The present study was designed to investigate the physiological and biochemical changes in rabbits after injection with the growth promoter BOL. A total of 32 adult New Zealand rabbits were divided into four groups, where the control group includes animals that were injected intramuscularly with olive oil and dissected after 3 weeks. The remaining three experimental groups included animals that received one, two and three intramuscular injections of 5 mg/kg body weight BOL, respectively, and were dissected after 3, 6 and 9 weeks, respectively. The animals from practice appeared healthy and did not show clinical signs of disease and none of the rabbits died during the experimental period. Serum total protein, globulin, alanine aminotransferase, asparate aminotransferase, urea, creatinine, testosterone, luteinizing hormone and follicle-stimulating hormone levels were significantly increased while serum direct bilirubin, albumin and albumin/globulin ratio were significantly decreased (p < 0.05) after one, two and three intramuscular injections of BOL as compared to their relative values in the control group. These findings explain the common phenomena in athletes and bodybuilders who suffer from infertility, renal and hepatic alterations following injection with some drugs as steroids (BOL) to build muscles. © The Author(s) 2013.

Antioxidant and anti-inflammatory effects of flavocoxid in high-cholesterol-fed rabbits.

PubMed

El-Sheakh, Ahmed R; Ghoneim, Hamdy A; Suddek, Ghada M; Ammar, El-Sayed M

2015-12-01

Flavocoxid is a mixed extract containing baicalin and catechin, and it acts as a dual balanced inhibitor of cyclooxygenase-1 (COX-1) and COX-2 peroxidase enzyme activities with a significant inhibition of 5-lipoxygenase (5-LOX) enzyme activity in vitro. Flavocoxid downregulates gene or protein expression of several inflammatory markers and exerts also strong antioxidant activity in several experimental models. Inflammation and oxidative stress contribute in the pathogenesis of atherosclerosis. In the present study, an experimental rabbit model of hypercholesterolemia was developed and the effects of flavocoxid were evaluated. Rabbits were divided into four groups-normal control, high-cholesterol-diet (HCD)-fed group, HCD plus flavocoxid (20 mg/kg/day), or HCD plus atorvastatin (10 mg/kg/day). Blood samples were collected at the end of the experiment for measuring serum total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP), malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD). In addition, the aorta was removed for measurement of antioxidant status, vascular reactivity, and intima/media (I/M) ratio. Elevated levels of serum TC, TGs, LDL-C, and CRP were measured in HCD group. Moreover, HCD caused a significant increase in serum and aortic MDA concomitantly with a reduction in serum and aortic GSH and SOD. Immunohistochemical staining of aortic specimens from HCD-fed rabbits revealed high expression levels of both tumor necrosis factor-alpha (TNF-α) and nuclear factor (NF)-κB. Rabbits in flavocoxid group showed significantly lower levels of serum CRP, serum, and aortic MDA and higher levels of serum HDL-C, serum, and aortic GSH and SOD compared to HCD group. HCD-induced elevations in serum TC and LDL-C did not significantly affected by flavocoxid treatment. Additionally, flavocoxid significantly enhanced rabbit aortic endothelium-dependent relaxation to acetylcholine and

The hepatoprotective role of Silymarin in isoniazid induced liver damage of rabbits.

PubMed

Jahan, Sarwat; Khan, Moosa; Imran, Sana; Sair, Mohammad

2015-06-01

To evaluate the hepatoprotective role of Silymarin against isonicotinylhydrazine-induced hepatotoxicity in rabbit model. The experimental animal study was held at Jinnah Postgraduate Medical Centre, Karachi, from April to September 2013 and comprised rabbits weighing 1-1.5kgof either gender. The animals were divided randomly into equal groups: group I underwent liver function test without any drug; in group II effects of Silymarin (50mg/kg/day orally) was observed; in group III isoniazid (50mg/kg/dayorally) was administered; and in group IV combined effects of isoniazid and silymarin were observed. Liver function tests were performed at day0 and after the treatment at day19. SPSS 16 was used for statistical analysis. The 28 rabbits in the study were divided in four groups of 7(25%) each. No mortality was recorded in any group. In group III, bilirubin level was increased and alanine transaminase was decreased significantly (p<0.05 each). In group IV, there was significant improvement in serum billirubin and serum alanine transaminase (p<0.05 each). Isonicotinylhydrazine-induced hepatotoxicity was well treated by concurrent administration of Silymarin.

Rank in Self-Defense Forces and risk factors for atherosclerotic disease.

PubMed

Sakuta, Hidenari; Suzuki, Takashi

2005-10-01

Socioeconomic status is associated with prevalence of and risk for atherosclerotic disease. We investigated the relationship between rank in the Self-Defense Forces (SDFs) and risk factors for atherosclerotic disease among middle-aged, male, SDFs personnel. Subjects were classified into five groups according to their ranks in the SDFs, i.e., class 1 (lowest, n = 289), class 2 (low, n = 170), class 3 (middle, n = 229), class 4 (high, n = 197), and class 5 (highest, n = 89). Low rank was associated with current cigarette smoking, alcohol abstaining, and poorer vegetable consumption. It was also associated with prevalence of type 2 diabetes, elevated gamma-glutamyltransferase activity, and high white blood cell counts. Prevalence of obesity, hypertension, hypercholesterolemia, hypertriglyceridemia, or hyperuricemia was not associated with rank in this population. Rank may be regarded as one of the markers that reflect individual health states among middle-aged male personnel.

Protection against myxomatosis and rabbit viral hemorrhagic disease with recombinant myxoma viruses expressing rabbit hemorrhagic disease virus capsid protein.

PubMed

Bertagnoli, S; Gelfi, J; Le Gall, G; Boilletot, E; Vautherot, J F; Rasschaert, D; Laurent, S; Petit, F; Boucraut-Baralon, C; Milon, A

1996-08-01

Two myxoma virus-rabbit hemorrhagic disease virus (RHDV) recombinant viruses were constructed with the SG33 strain of myxoma virus to protect rabbits against myxomatosis and rabbit viral hemorrhagic disease. These recombinant viruses expressed the RHDV capsid protein (VP60). The recombinant protein, which is 60 kDa in size, was antigenic, as revealed by its reaction in immunoprecipitation with antibodies raised against RHDV. Both recombinant viruses induced high levels of RHDV- and myxoma virus-specific antibodies in rabbits after immunization. Inoculations by the intradermal route protected animals against virulent RHDV and myxoma virus challenges.

Experience With Intravascular Ultrasound Imaging Of Human Atherosclerotic Arteries

NASA Astrophysics Data System (ADS)

Mallery, John A.; Gessert, James M.; Maciel, Mario; Tobis, John M.; Griffith, James M.; Berns, Michael W.; Henry, Walter L.

1989-08-01

Normal human arteries have a well-defined structure on intravascular images. The intima appears very thin and is most likely represented by a bright reflection arising from the internal elastic lamina. The smooth muscle tunica media is echo-lucent on the ultrasound image and appears as a dark band separating the intima from the adventitia. The adventitia is a brightly reflective layer of variable thickness. The thickness of the intima, and therefore of the atherosclerotic plaque can be accurately measured from the ultrasound images and correlates well with histology. Calcification within the wall of arteries is seen as bright echo reflection with shadowing of the peripheral wall. Fibrotic regions are highly reflective but do not shadow. Necrotic liquid regions within advanced atherosclerotic plaques are seen on ultrasound images as large lucent zones surrounded by echogenic tissue. Imaging can be performed before and after interventional procedures, such as laser angioplasty, balloon angioplasty and atherectomy. Intravascular ultrasound appears to provide an imaging modality for identifying the histologic characteristics of diseased arteries and for quantifying plaque thickness. It might be possible to perform such quantification to evaluate the results of interventional procedures.

Engineering adeno-associated virus 2 vectors for targeted gene delivery to atherosclerotic lesions.

PubMed

White, K; Büning, H; Kritz, A; Janicki, H; McVey, J; Perabo, L; Murphy, G; Odenthal, M; Work, L M; Hallek, M; Nicklin, S A; Baker, A H

2008-03-01

Targeted delivery of biological agents to atherosclerotic plaques may provide a novel treatment and/or useful tool for imaging of atherosclerosis in vivo. However, there are no known viral vectors that possess the desired tropism. Two plaque-targeting peptides, CAPGPSKSC (CAP) and CNHRYMQMC (CNH) were inserted into the capsid of adeno-associated virus 2 (AAV2) to assess vector retargeting. AAV2-CNH produced significantly higher levels of transduction than unmodified AAV2 in human, murine and rat endothelial cells, whereas transduction of nontarget HeLa cells was unaltered. Transduction studies and surface plasmon resonance suggest that AAV2-CNH uses membrane type 1 matrix metalloproteinase as a surface receptor. AAV2-CAP only produced higher levels of transduction in rat endothelial cells, possibly because the virus was found to be affected by proteasomal degradation. In vivo substantially higher levels of both peptide-modified AAV2 vectors was detected in the brachiocephalic artery (site of advanced atherosclerotic plaques) and aorta, whereas reduced levels were detected in all other organs examined. These results suggest that in the AAV2 platform the peptides are exposed on the capsid surface in a way that enables efficient receptor binding and so creates effective atherosclerotic plaque targeted vectors.

Effect of Watermarking on Diagnostic Preservation of Atherosclerotic Ultrasound Video in Stroke Telemedicine.

PubMed

Dey, Nilanjan; Bose, Soumyo; Das, Achintya; Chaudhuri, Sheli Sinha; Saba, Luca; Shafique, Shoaib; Nicolaides, Andrew; Suri, Jasjit S

2016-04-01

Embedding of diagnostic and health care information requires secure encryption and watermarking. This research paper presents a comprehensive study for the behavior of some well established watermarking algorithms in frequency domain for the preservation of stroke-based diagnostic parameters. Two different sets of watermarking algorithms namely: two correlation-based (binary logo hiding) and two singular value decomposition (SVD)-based (gray logo hiding) watermarking algorithms are used for embedding ownership logo. The diagnostic parameters in atherosclerotic plaque ultrasound video are namely: (a) bulb identification and recognition which consists of identifying the bulb edge points in far and near carotid walls; (b) carotid bulb diameter; and (c) carotid lumen thickness all along the carotid artery. The tested data set consists of carotid atherosclerotic movies taken under IRB protocol from University of Indiana Hospital, USA-AtheroPoint™ (Roseville, CA, USA) joint pilot study. ROC (receiver operating characteristic) analysis was performed on the bulb detection process that showed an accuracy and sensitivity of 100 % each, respectively. The diagnostic preservation (DPsystem) for SVD-based approach was above 99 % with PSNR (Peak signal-to-noise ratio) above 41, ensuring the retention of diagnostic parameter devalorization as an effect of watermarking. Thus, the fully automated proposed system proved to be an efficient method for watermarking the atherosclerotic ultrasound video for stroke application.

Innate resistance to myxomatosis in wild rabbits in England.

PubMed

Ross, J; Sanders, M F

1977-12-01

Wild rabbits (Oryctolagus cuniculus) from one study area in England have been used over a period of 11 years to investigate the possible appearance of innate resistance to myxomatosis. Rabbits of 4-6 weeks old were captured alive, retained in the laboratory until at least 4 months old, and then infected with a type of myxoma virus which kills 90-95% of laboratory rabbits. Observations were made of symptoms, mortality rate and survival times.In the first 4 years of the study (1966-9), mortality rates were not significantly different from those of laboratory rabbits, although survival times of wild rabbits were appreciably longer. In 1970, the mortality rate amongst wild rabbits was 59%, in 1974 it was 17%, and in 1976 it was 20%, thus showing that a considerable degree of inherited resistance to myxomatosis has developed.The types of myxoma virus most commonly isolated from wild rabbits in Great Britain in recent years have been those which cause 70-95% mortality in laboratory rabbits. Therefore, if the degree of innate resistance demonstrated is widespread in Great Britain, there are serious implications regarding the size of the rabbit population, because myxomatosis has been an important factor in holding rabbit numbers at a relatively low level.

Innate resistance to myxomatosis in wild rabbits in England*

PubMed Central

Ross, J.; Sanders, M. F.

1977-01-01

Wild rabbits (Oryctolagus cuniculus) from one study area in England have been used over a period of 11 years to investigate the possible appearance of innate resistance to myxomatosis. Rabbits of 4-6 weeks old were captured alive, retained in the laboratory until at least 4 months old, and then infected with a type of myxoma virus which kills 90-95% of laboratory rabbits. Observations were made of symptoms, mortality rate and survival times. In the first 4 years of the study (1966-9), mortality rates were not significantly different from those of laboratory rabbits, although survival times of wild rabbits were appreciably longer. In 1970, the mortality rate amongst wild rabbits was 59%, in 1974 it was 17%, and in 1976 it was 20%, thus showing that a considerable degree of inherited resistance to myxomatosis has developed. The types of myxoma virus most commonly isolated from wild rabbits in Great Britain in recent years have been those which cause 70-95% mortality in laboratory rabbits. Therefore, if the degree of innate resistance demonstrated is widespread in Great Britain, there are serious implications regarding the size of the rabbit population, because myxomatosis has been an important factor in holding rabbit numbers at a relatively low level. PMID:270526

[An experimental study of ocular contusion in rabbits: the changes in electroretinography].

PubMed

Dou, H L; Song, C

1993-07-01

In rabbits, the amplitude of a-waves and b-waves in the ERG declined following ocular contusion; however, the oscillatory potentials did not change markedly. In the anisodine therapeutic group, the amplitude of a-waves recovered higher than did that in the control group at the 2nd and 4th week post-traumatic, while all a-waves recovered at the 6th week in both groups. The amplitude of b-waves was restored to normal in 72 hours for all eyes. Since the a-wave was sensitive to contusion, it monitored the severity of damage and objectively evaluated the therapeutic effect of treatment.

Anterior segment changes in rabbits after experimental aqueous replacement with various amounts of different perfluorocarbon liquids.

PubMed

Stolba, U; Krepler, K; Velikay, M; Binder, S

1999-06-01

We evaluated biomicroscopic and histological effects on the anterior segment in the rabbit eye after temporary aqueous substitution with various amounts (0.2 cc and 0.025 cc) of perfluorodecaline (PFD) and perfluorophenanthrene (PFP). A quantity of 0.2 cc of the two perfluorocarbon (PFC) liquids was exchanged simultaneously with about 50% of the aqueous in 15 rabbit eyes each for periods of 1, 2, or 4 weeks. At these points some eyes were enucleated for histological examination. After 2 and 4 weeks the substances were removed from the remaining eyes, which were then followed up for 8-10 weeks. In an additional 8 eyes, 0.025 cc PFD or PFP was injected and left for 8 weeks. Four eyes received balanced salt solution and served as controls. Beside biomicroscopic evaluation and measurement of the intraocular pressure, endothelial cell counts and corneal pachymetry were performed regularly during follow-up. The postoperative results were well comparable for PFD and PFP eyes. Within the first 2 weeks postoperatively corneal edema with endothelial cell loss was observed in both groups. Thereafter regression of the edema started independently of whether the substances were removed or not. IOP was not elevated at any time. At the end of follow-up central corneal thickness was the same as initially. In the inferior corneal endothelium cell density decreased to 45-50% of that in normals. Histologically, vacuoles in the iris and chamber angle were found inferiorly after 4 weeks. Chamber angle closures were present between 5 and 7 o'clock in those eyes where the PFC liquids had been removed after 2 and 4 weeks. Eyes with 0.025 cc PFD or PFP droplets showed vacuolization of the inferior trabecular meshwork 8 weeks postoperatively that was comparable with eyes which had a 50% aqueous replacement for 4 weeks. Control eyes remained unchanged in all aspects. Anterior segment damage caused by PFC liquids is a contact-dependent effect seen in the early observation period

Manipulations of core temperatures in ischemia-reperfusion lung injury in rabbits.

PubMed

Chang, Hung; Huang, Kun-Lun; Li, Min-Hui; Hsu, Ching-Wang; Tsai, Shih-Hung; Chu, Shi-Jye

2008-01-01

The present study was designed to determine the effect of various core temperatures on acute lung injury induced by ischemia-reperfusion (I/R) in our isolated rabbit lung model. Typical acute lung injury was successfully induced by 30 min of ischemia followed by 90 min of reperfusion observation. The I/R elicited a significant increase in pulmonary arterial pressure, microvascular permeability (measured by using the capillary filtration coefficient, Kfc), Delta Kfc ratio, lung weight gain and the protein concentration of the bronchoalveolar lavage fluid. Mild hypothermia significantly attenuated acute lung injury induced by I/R, all parameters having decreased significantly (p<0.05); conversely, mild hyperthermia did not further exacerbate acute lung injury. These experimental data suggest that mild hypothermia significantly ameliorated acute lung injury induced by ischemia-reperfusion in rabbits.

Human Handling Promotes Compliant Behavior in Adult Laboratory Rabbits

PubMed Central

Swennes, Alton G; Alworth, Leanne C; Harvey, Stephen B; Jones, Carolyn A; King, Christopher S; Crowell-Davis, Sharon L

2011-01-01

Routine laboratory procedures can be stressful for laboratory animals. We wanted to determine whether human handling of adult rabbits could induce a degree of habituation, reducing stress and facilitating research-related manipulation. To this end, adult New Zealand white rabbits were handled either frequently or minimally. After being handled over 3 wk, these rabbits were evaluated by novel personnel and compared with minimally handled controls. Evaluators subjectively scored the rabbits for their relative compliance or resistance to being scruffed and removed from their cages, being transported to a treatment room, and their behavior at all stages of the exercise. Upon evaluation, handled rabbits scored significantly more compliant than nontreated controls. During evaluation, behaviors that the rabbits displayed when they were approached in their cages and while being handled outside their cages were recorded and compared between study groups. Handled rabbits displayed behavior consistent with a reduction in human-directed fear. This study illustrates the potential for handling to improve compliance in laboratory procedures and reduce fear-related behavior in laboratory rabbits. Such handling could be used to improve rabbit welfare through the reduction of stress and exposure to novel stimuli. PMID:21333162

Effect of vacuum-assisted closure combined with open bone grafting to promote rabbit bone graft vascularization.

PubMed

Hu, Chao; Zhang, Taogen; Ren, Bin; Deng, Zhouming; Cai, Lin; Lei, Jun; Ping, Ansong

2015-04-27

Patients with composite bone non-union and soft tissue defects are difficult to treat. Vacuum-assisted closure (VAC) combined with open bone grafting is one of the most effective treatments at present. The aim of the present study was to preliminarily investigate the effect and mechanism of VAC combined with open bone grafting to promote rabbit bone graft vascularization, and to propose a theoretical basis for clinical work. Twenty-four New Zealand white rabbits were randomly divided into an experimental and a control group. Allogeneic bones were grafted and banded with the proximal femur with a suture. The experimental group had VAC whereas the control group had normal wound closure. The bone vascularization rate was compared based on X-ray imaging, fluorescent bone labeling (labeled tetracycline hydrochloride and calcein), calcium content in the callus, and expression of fibroblast growth factor-2 (FGF-2) in bone allografts by Western blot analysis at the 4th, 8th, and 12th week after surgery. At the 4th, 8th, and 12th week after surgery, the results of the tests demonstrated that the callus was larger, contained more calcium (p<0.05), and expressed FGF-2 at higher levels (p<0.05) in the experimental group than in the control group. Fluorescent bone labeling showed the distance between the two fluorescent ribbons was significantly shorter in the control group than in the experimental group at the 8th and 12th week after surgery. VAC combined with open bone grafting promoted rabbit bone graft vascularization.

New methods for time-resolved fluorescence spectroscopy data analysis based on the Laguerre expansion technique--applications in tissue diagnosis.

PubMed

Jo, J A; Marcu, L; Fang, Q; Papaioannou, T; Qiao, J H; Fishbein, M C; Beseth, B; Dorafshar, A H; Reil, T; Baker, D; Freischlag, J

2007-01-01

A new deconvolution method for the analysis of time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) data is introduced and applied for tissue diagnosis. The intrinsic TR-LIFS decays are expanded on a Laguerre basis, and the computed Laguerre expansion coefficients (LEC) are used to characterize the sample fluorescence emission. The method was applied for the diagnosis of atherosclerotic vulnerable plaques. At a first stage, using a rabbit atherosclerotic model, 73 TR-LIFS in-vivo measurements from the normal and atherosclerotic aorta segments of eight rabbits were taken. The Laguerre deconvolution technique was able to accurately deconvolve the TR-LIFS measurements. More interesting, the LEC reflected the changes in the arterial biochemical composition and provided discrimination of lesions rich in macrophages/foam-cells with high sensitivity (> 85%) and specificity (> 95%). At a second stage, 348 TR-LIFS measurements were obtained from the explanted carotid arteries of 30 patients. Lesions with significant inflammatory cells (macrophages/foam-cells and lymphocytes) were detected with high sensitivity (> 80%) and specificity (> 90%), using LEC-based classifiers. This study has demonstrated the potential of using TR-LIFS information by means of LEC for in vivo tissue diagnosis, and specifically for detecting inflammation in atherosclerotic lesions, a key marker of plaque vulnerability.

Increase in the adhesion molecule P-selectin in endothelium overlying atherosclerotic plaques. Coexpression with intercellular adhesion molecule-1.

PubMed Central

Johnson-Tidey, R. R.; McGregor, J. L.; Taylor, P. R.; Poston, R. N.

1994-01-01

P-selectin (GMP-140) is an adhesion molecule present within endothelial cells that is rapidly translocated to the cell membrane upon activation, where it mediates endothelial-leukocyte interactions. Immunohistochemical analysis of human atherosclerotic plaques has shown strong expression of P-selectin by the endothelium overlying active atherosclerotic plaques. P-selectin is not, however, detected in normal arterial endothelium or in endothelium overlying inactive fibrous plaques. Color image analysis was used to quantitate the degree of P-selectin expression in the endothelium and demonstrates a statistically significant increase in P-selectin expression by atherosclerotic endothelial cells. Double immunofluorescence shows that some of this P-selectin is expressed on the luminal surface of the endothelial cells. Previous work has demonstrated a significant up-regulation in the expression of the intercellular adhesion molecule-1 in atherosclerotic endothelium and a study on the expression of intercellular adhesion molecule-1 and P-selectin in atherosclerosis shows a highly positive correlation. These results suggest that the selective and cooperative expression of P-selectin and intercellular adhesion molecule-1 may be involved in the recruitment of monocytes into sites of atherosclerosis. Images Figure 1 Figure 3 Figure 4 Figure 5 PMID:7513951

Protection against myxomatosis and rabbit viral hemorrhagic disease with recombinant myxoma viruses expressing rabbit hemorrhagic disease virus capsid protein.

PubMed Central

Bertagnoli, S; Gelfi, J; Le Gall, G; Boilletot, E; Vautherot, J F; Rasschaert, D; Laurent, S; Petit, F; Boucraut-Baralon, C; Milon, A

1996-01-01

Two myxoma virus-rabbit hemorrhagic disease virus (RHDV) recombinant viruses were constructed with the SG33 strain of myxoma virus to protect rabbits against myxomatosis and rabbit viral hemorrhagic disease. These recombinant viruses expressed the RHDV capsid protein (VP60). The recombinant protein, which is 60 kDa in size, was antigenic, as revealed by its reaction in immunoprecipitation with antibodies raised against RHDV. Both recombinant viruses induced high levels of RHDV- and myxoma virus-specific antibodies in rabbits after immunization. Inoculations by the intradermal route protected animals against virulent RHDV and myxoma virus challenges. PMID:8764013

[An experimental study of mesenchymal stem cells in tissue engineering scaffolds implanted in rabbit corneal lamellae to increase keratoprosthesis biointegration].

PubMed

Bai, H; Wang, L L; Huang, Y F; Huang, J X

2016-03-01

To complete a preliminary evaluation of the feasibility of implanting the complex of mouse bone marrow mesenchymal stem cells (BMSC) and a tissue engineering scaffold into rabbit corneal lamellae, based on which a solution may be proposed to consolidate the keratoprosthesis and the recipient surface, and to reduce the risk of complications. This experimental study was composed of two parts. (1) In vitro: some mouse BMSC were marked with red fluorescent proteins (RFP) and integrated with a decellularized pig articular cartilage extracellular matrix (ECM) scaffold. The cell survival was observed under a fluorescence microscope at 4 and 8 weeks. The cell distribution was examined by toluidine blue staining. The pore structure and the cell adhesion were observed under a scanning electron microscope. (2) in vivo: the complex of mouse BMSC and a decellularized scaffold was implanted into the lamellar cornea of 8 rabbit eyes with the fellow eyes as the controls. The eyes were sampled for observation using HE staining under a light microscope at 2, 4 and 8 weeks, respectively. The cell survival was examined under a fluorescence microscope, and the intracorneal cell survival at 8 weeks was observed using in vivo imaging. The conditions of ocular anterior segment of all the experimental animals were recorded. (1) Under the scanning electron microscope, the ECM scaffolds showed satisfactory porosity required for the adhesion and growth of cells and tissues, and the cell distribution over the cell-scaffold complex can be observed by toluidine blue staining. (2) Under the immunofluorescence microscope, cell proliferation was observed in vitro and in the interlamellar space (the maximum observation time was 8 weeks) after the RFP-marked mouse BMSC were integrated in vitro with ECM scaffolds. (3) Under the light microscope (HE staining), the stromal cells were detected to increase at each timepoint. A small number of monocytes and some mouse BMSC were observed in the superficial

Conjunctival Expansion Using a Subtenon's Silicone Implant in New Zealand White Rabbits

PubMed Central

Yoon, Ie-na; Lee, Dong-hoon

2007-01-01

Purpose In the field of ophthalmology, the conjunctival autograft is a useful therapeutic material in many cases, but the small size of the autograft is a disadvantage. Therefore, we evaluated the feasibility of taking an expanded sample of conjunctival tissue using a subtenon's silicone implant. Materials and Methods We included a total of nine rabbits; eight rabbits were operative cases, and one was a control. A portion of conjunctival tissue from the control rabbit, which did not undergo surgery, was dissected and examined to determine whether it was histologically different from the experimental group. The surgical procedure was performed on eight rabbits via a subtenon's insertion of a silicone sponge in the left superior-temporal portion; after surgery, we dropped antibiotics into the eyes. We sacrificed a pair of rabbits every three days (on days 3, 6, 9, and 12) after surgery, removed the expanded conjunctival tissues with the silicone sponge implants, and measured their sizes. Results The mean size of the expanded conjunctival tissues was 194.4 mm2. On the third day, we were able to harvest a 223.56 mm2 section of conjunctival tissue, which was the most expanded sample of tissue in the study. On the twelfth day, we removed a 160.38 mm2 section of conjunctival tissue, which was the least expanded sample of tissue. Statistically, there were no significant differences in the mean dimensions of the expanded conjunctival tissues for each time period. Microscopic examinations showed no histological differences between the expanded conjunctival tissues and the normal conjunctival tissues. Conclusion The results reveal that this procedure is a useful method to expand the conjunctiva for grafting and transplantation. PMID:18159586

High purity tocotrienols attenuate atherosclerotic lesion formation in apoE-KO mice.

PubMed

Shibata, Akira; Kobayashi, Teiko; Asai, Akira; Eitsuka, Takahiro; Oikawa, Shinichi; Miyazawa, Teruo; Nakagawa, Kiyotaka

2017-10-01

Previous studies have demonstrated that tocotrienol (T3) has antiatherogenic effects. However, the T3 preparations used in those studies contained considerable amounts of tocopherol (Toc), which might affect the biological activity of T3. There is little information on the effect of highly purified T3 on atherosclerosis formation. This study investigated the effect of high-purity T3 on atherosclerotic lesion formation and the underlying mechanisms. Male apolipoprotein E knockout (apoE-KO) mice were fed a cholesterol-containing diet either alone or supplemented with T3 concentrate (Toc-free T3) or with α-Toc for 12 weeks. ApoE-KO mice fed the 0.2% T3-supplemented diet showed reduced atherosclerotic lesion formation in the aortic root. The 0.2% T3 diet induced Slc27a1 and Ldlr gene expression levels in the liver, whereas the α-Toc-supplemented diet did not affect those expression levels. T3 was predominantly deposited in fat tissue in the T3 diet-fed mice, whereas α-Toc was preferentially accumulated in liver in the α-Toc diet-fed mice. Considered together, these data demonstrate that dietary T3 exerts anti-atherosclerotic effect in apoE-KO mice. The characteristic tissue distribution and biological effects of T3, that are substantially different from those of Toc, may contribute to the antiatherogenic properties of T3. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed Central

2016-01-01

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

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

PubMed

Gray, Richard A; Pathmanathan, Pras

2016-10-01

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

Morbidity and mortality associated with creation of elastase-induced saccular aneurysms in a rabbit model

PubMed Central

Lewis, Debra A; Ding, Yong Hong; Dai, Daying; Kadirvel, Ramanathan; Danielson, Mark A; Cloft, Harry J; Kallmes, David F

2008-01-01

Background and Purpose Elastase-induced aneurysms in rabbits have been proposed as a useful preclinical tool for device development. The object of this study is to report rates of morbidity and mortality associated with creation and embolization of the elastase-induced rabbit aneurysm, and to assess the impact of operator experience on these rates. Methods Elastase-induced model aneurysms were created in New Zealand White rabbits (n=700). One neuroradiologist/investigator, naïve to the aneurysm creation procedure at the outset of the experiments, performed all surgeries. All morbidity and deaths related to aneurysm creation (n=700) and embolization procedures (n=529) were categorized into acute and chronic deaths. Data were analyzed with single regression analysis and ANOVA. To assess the impact of increasing operator experience, the number of animals was broken into 50 animal increments. Results There were 121 (17%) deaths among 700 subjects. Among 700 aneurysm creation procedures, 59 deaths (8.4%) were noted. Among 529 aneurysm embolization procedures, 43 deaths (8.1%) were noted. Nineteen additional deaths (2.7% of 700 subjects) were unrelated to procedures. Simple regression indicated mortality associated with procedures diminished with increasing operator experience (R2=0.38; p=0.0180) and that for each 50 rabbit increment mortality is reduced on average by 0.6 percent. Conclusions Mortality rates of approximately 8% are associated with both experimental aneurysm creation and with embolization in the rabbit, elastase-induced aneurysm model. Increasing operator experience is inversely correlated with mortality and the age of the rabbit is positively associated with morbidity. PMID:19001536

Iodine-125 Seeds Strand for Treatment of Tumor Thrombus in Inferior Vena Cava: An Experimental Study in a Rabbit Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Wen, E-mail: wenzhangxiao@126.com; Yan, Zhiping, E-mail: Yan.zhiping@zs-hospital.sh.cn; Luo, Jianjun, E-mail: luo.jianjun@zs-hospital.sh.cn

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,more » 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

[Changes of structures of anterior chamber angle in rabbit chronic high intraocular pressure model].

PubMed

Lei, Xun-wen; Wei, Ping; Li, Xiao-lin; Yang, Kan; Lei, Jian-zhen

2009-10-01

To observe the anterior chamber angle changes occurred in compound Carbomer-induced chronic high intraocular pressure (IOP) model in rabbit eyes. It was an experimental study. Thirty two rabbits were randomly divided into eight groups. Compound Carbomer (0.3%, 0.3 ml) was injected into the left anterior chamber. A group of rabbits were randomly killed after 1, 2, 3, 4, 6, 8, 10 and 12 weeks. The anterior chamber of the rabbit eye specimens was observed. IOP increased slowly following the application of the drug, high IOP lasted for 3 months. The drug-induced changes of anterior chamber angle consisted of early inflammatory response and late fibrous changes. Inflammatory response occurred in early stage and reduced or disappeared after 3 weeks. Fibrous degeneration and adhesion obstruction occurred in the anterior chamber angle after 4 weeks. Under the electron microscope, the trabecular was expanded and deformed, with hyperplasia of collagen and elastic fibers. Endothelial cells were separated from the trabecular, and showed the morphology of lymphocytes, with the function similar to the macrophages. Phagocytized Carbomer particles were transported through the vacuoles of Schlemm's canal endothelial cells. Large vacuoles gradually reduced. Excessive Carbomer particles were accumulated in the endothelial cells and obstructed the Schlemm's canal. This induced the fibrous proliferation and the destruction of anterior chamber angle structures. The obstruction of aqueous humor outflow induced by compound Carbomer in rabbit high IOP model is caused mainly by the changes in trabecular endothelial cells.

The effect of thalidomide on spinal cord ischemia/reperfusion injury in a rabbit model.

PubMed

Lee, C-J; Kim, K-W; Lee, H-M; Nahm, F S; Lim, Y-J; Park, J-H; Kim, C-S

2007-02-01

Randomized study. To evaluate the effects of thalidomide on spinal cord ischemia/reperfusion injury via reduced TNF-alpha production. Animal experimental laboratory, Clinical Research Institute of Seoul National University Hospital, Seoul, Korea. Spinal cord ischemia was induced in rabbits by occluding the infrarenal aorta. Rabbits in group N did not undergo ischemic insult, but rabbits in groups C (the untreated group), THA, and THB underwent ischemic insult for 15 min. The THA and THB groups received thalidomide (20 mg/kg) intraperitoneally (i.p.) before ischemia, but only the THB group received thalidomide (i.p., 20 mg/kg) after 24 and 48 h of reperfusion. After evaluating neurologic functions at 1.5 h, 3, and 5 days of reperfusion, rabbits were killed for histopathologic examination and Western blot analysis of TNF-alpha. The THA and THB groups showed significantly less neurologic dysfunction than the C group at 1.5 h, 3, and 5 days of reperfusion. The number of normal spinal motor neurons in ventral gray matter was higher in THA and THB than in C, but no difference was observed between THA and THB. Western blot analysis showed a significantly higher level of TNF-alpha in C than in THA and THB at 1.5 h of reperfusion, but no difference was observed between C, THA, or THB at 3 or 5 days of reperfusion. Thalidomide treatment before ischemic insult reduces early phase ischemia/reperfusion injury of the spinal cord in rabbits.

Safety study of intravitreal and suprachoroidal Laponite clay in rabbit eyes.

PubMed

Prieto, Esther; Vispe, Eugenio; De Martino, Alba; Idoipe, Miriam; Rodrigo, María J; Garcia-Martin, Elena; Fraile, José M; Polo-Llorens, Vicente; Mayoral, José A

2018-03-01

To study the safety and biocompatibility of Laponite clay (LAP) within an intravitreal and suprachoroidal administration in rabbit eyes. Thirty-two New Zealand albino rabbits were divided into two experimental groups to test intravitreal (IVT group) and suprachoroidal (SCS group) administration of a 100-μl and 50-μl Laponite suspension respectively. Following injection, the eyes were monitored by ocular tonometry, slit-lamp eye examination and indirect ophthalmoscopy, at 24 h, 1, 4, 12, and 14 weeks post administration. Histological examination was also performed to determine whether any ocular pathological change had occurred. Throughout the study, LAP presence in vitreous was estimated by complexometric titration with ethylenediaminetetraacetic acid (EDTA), taking advantage of the Laponite high content of magnesium ions. Neither significant differences in the intraocular pressure, nor relevant ocular complications were found in the two experimental groups after LAP administration. The histology of the retina remained unchanged. LAP presence in vitreous could be indirectly confirmed by complexometric titration until 14 weeks post administration in eyes of IVT group. Laponite could be considered as a vehicle for potential clinical use in ocular drug administration, due to its proven ocular biocompatibility and its transparency in gel state.

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

PubMed

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

2008-12-01

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

Bobcat attack on a cottontail rabbit

USGS Publications Warehouse

Biggins, D.E.; Biggins, D.M.

2006-01-01

We observed an attack by a bobcat (Lynx rufus) on a cottontail rabbit (Sylvilagus) that involved stealthy approach by the cat for >1 h, followed by a 12.3-s chase covering 116.0 m for the cat and 128.4 m for the rabbit. During the chase, the route of the cat from starting point to kill site was more direct than the semi-circular route of the rabbit. Stride lengths for the cat and total distance covered by the chase were longer than those previously reported for bobcats.

Characteristics of MIC-1 antlerogenic stem cells and their effect on hair growth in rabbits.

PubMed

Cegielski, Marek; Izykowska, Ilona; Chmielewska, Magdalena; Dziewiszek, Wojciech; Bochnia, Marek; Calkosinski, Ireneusz; Dziegiel, Piotr

2013-01-01

We characterized growth factors produced by MIC-1 antlerogenic stem cells and attempted to apply those cells to stimulate hair growth in rabbits. We evaluated the gene and protein expression of growth factors by immunocytochemical and molecular biology techniques in MIC-1 cells. An animal model was used to assess the effects of xenogenous stem cells on hair growth. In the experimental group, rabbits were intradermally injected with MIC-1 stem cells, whereas the control group rabbits were given vehicle-only. After 1, 2 and 4 weeks, skin specimen were collected for histological and immunohistochemical tests. MIC-1 antlerogenic stem cells express growth factors, as confirmed at the mRNA and protein levels. Histological and immunohistochemical analysis demonstrated an increase in the number of hair follicles, as well as the amount of secondary hair in the follicles, without an immune response in animals injected intradermally with MIC-1 cells, compared to animals receiving vehicle-alone. MIC-1 cells accelerated hair growth in rabbits due to the activation of cells responsible for the regulation of the hair growth cycle through growth factors. Additionally, the xenogenous cell implant did not induce immune response.

Molecular cloning and biochemical characterization of rabbit factor XI.

PubMed Central

Sinha, Dipali; Marcinkiewicz, Mariola; Gailani, David; Walsh, Peter N

2002-01-01

Human factor XI, a plasma glycoprotein required for normal haemostasis, is a homodimer (160 kDa) formed by a single interchain disulphide bond linking the Cys-321 of each Apple 4 domain. Bovine, porcine and murine factor XI are also disulphide-linked homodimers. Rabbit factor XI, however, is an 80 kDa polypeptide on non-reducing SDS/PAGE, suggesting that rabbit factor XI exists and functions physiologically either as a monomer, as does prekallikrein, a structural homologue to factor XI, or as a non-covalent homodimer. We have investigated the structure and function of rabbit factor XI to gain insight into the relation between homodimeric structure and factor XI function. Characterization of the cDNA sequence of rabbit factor XI and its amino acid translation revealed that in the rabbit protein a His residue replaces the Cys-321 that forms the interchain disulphide linkage in human factor XI, explaining why rabbit factor XI is a monomer in non-reducing SDS/PAGE. On size-exclusion chromatography, however, purified plasma rabbit factor XI, like the human protein and unlike prekallikrein, eluted as a dimer, demonstrating that rabbit factor XI circulates as a non-covalent dimer. In functional assays rabbit factor XI and human factor XI behaved similarly. Both monomeric and dimeric factor XI were detected in extracts of cells expressing rabbit factor XI. We conclude that the failure of rabbit factor XI to form a covalent homodimer due to the replacement of Cys-321 with His does not impair its functional activity because it exists in plasma as a non-covalent homodimer and homodimerization is an intracellular process. PMID:12084014

Micro-optical fiber probe for use in an intravascular Raman endoscope.

PubMed

Komachi, Yuichi; Sato, Hidetoshi; Aizawa, Katsuo; Tashiro, Hideo

2005-08-01

We believe that we have developed the narrowest optical-fiber Raman probe ever reported, 600 microm in total diameter, that can be inserted into coronary arteries. The selection of suitable optical fibers, filters, and a processing method is discussed. Custom-made filters attached to the front end of a probe eliminate the background Raman signals of the optical fiber itself. The experimental evaluation of various optical fibers is carried out for the selection of suitable fibers. Measurement of the Raman spectra of an atherosclerotic lesion of a rabbit artery in vitro demonstrates the excellent performance of the micro-Raman probe.

Detection of atherosclerotic lesions and intimal macrophages using CD36-targeted nanovesicles

USDA-ARS?s Scientific Manuscript database

Current approaches to the diagnosis and therapy of atherosclerosis cannot target to lesion-determinant cells in the artery wall. Intimal macrophage infiltration promotes atherosclerotic lesion development by facilitating the accumulation of oxidized low-density lipoproteins (oxLDL) and increasing in...

9 CFR 354.124 - Quarantine of diseased rabbits.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Quarantine of diseased rabbits. 354.124 Section 354.124 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... Procedures; Ante-Mortem Inspections § 354.124 Quarantine of diseased rabbits. If live rabbits, which are...

9 CFR 354.124 - Quarantine of diseased rabbits.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Quarantine of diseased rabbits. 354.124 Section 354.124 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... Procedures; Ante-Mortem Inspections § 354.124 Quarantine of diseased rabbits. If live rabbits, which are...

9 CFR 354.124 - Quarantine of diseased rabbits.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Quarantine of diseased rabbits. 354.124 Section 354.124 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF... Procedures; Ante-Mortem Inspections § 354.124 Quarantine of diseased rabbits. If live rabbits, which are...

In vivo and in vitro effects of selected antioxidants on rabbit meat microbiota.

PubMed

Albonetti, Sabrina; Minardi, Paola; Trombetti, Fabiana; Savigni, Fabiana; Mordenti, Attilio Luigi; Baranzoni, Gian Marco; Trivisano, Carlo; Greco, Fedele Pasquale; Badiani, Anna

2017-01-01

The purpose of this study was to investigate the effect of dietary vitamin E or EconomasE™ supplementation on the growth of several background/pathogenic bacteria on rabbit carcasses and hamburgers during refrigerated storage. For 51days, 270 New Zealand rabbits received either a basal diet, or experimental diets enriched with 100 or 200mg/kg of vitamin E or EconomasE™. The bacteria studied were Salmonella, Listeria monocytogenes, Pseudomonas, Enterobacteriaceae, Escherichia coli, coagulase-positive staphylococci, plus both mesophilic and psychrotrophic aerobes. The growth of Listeria monocytogenes on contaminated patties was evaluated through a challenge test. The potential protective or antimicrobial effect of vitamin E or EconomasE™ on Listeria monocytogenes or Pseudomonas aeruginosa was assessed in vitro. Diet did not influence the concentrations of bacteria found on rabbit carcasses and developing on hamburgers. Vitamin E (in vivo and in vitro) and EconomasE™ in vivo had a protective antioxidant role, while EconomasE™ in vitro had strong antibacterial activity against Listeria monocytogenes, but not against Pseudomonas aeruginosa. Copyright © 2016 Elsevier Ltd. All rights reserved.

Reduction of enhanced rabbit intraocular pressure by instillation of pyroglutamic acid eye drops.

PubMed

Ito, Yoshimasa; Nagai, Noriaki; Okamoto, Norio; Shimomura, Yoshikazu; Nakanishi, Kunio; Tanaka, Ryuichiro

2013-01-01

L-Pyroglutamic acid (PGA) is an endogenous molecule derived from l-glutamate. We demonstrate the effects of PGA on intraocular pressure (IOP) in experimentally induced ocular hypertension in rabbits. In the in vitro and in vivo transcorneal penetration studies, the PGA solution (PGA in saline) did not penetrate the rabbit cornea. On the other hand, the penetration of PGA was improved by the addition of zinc chloride and 2-hydroxypropyl-β-cyclodextrin (HPCD), and PGA penetration was enhanced with increasing HPCD concentration. Therefore, PGA solutions containing 0.5% zinc chloride and 5% or 10% HPCD (PGA/HPCD(5% or 10%) eye drops) were used to investigate the effects for IOP in this study. An elevation in IOP was induced by the rapid infusion of 5% glucose solution (15 mL/kg of body weight) through the marginal ear vein or maintaining under dark phase for 5 h. In the both models, the induced elevation in IOP was prevented by the instillation of PGA/HPCD eye drops, and the IOP-reducing effect enhanced with increasing HPCD concentration in the drops. Nitric oxide (NO) levels elevated in the aqueous humor following the infusion of 5% glucose solution, and this increase was also suppressed by the instillation of PGA/HPCD eye drops. In conclusion, the present study demonstrates that the instillation of PGA/HPCD eye drops has an IOP-reducing effect in rabbits with experimentally induced ocular hypertension, probably as a result of the suppression of NO production.

Incremental value of live/real time three-dimensional transesophageal echocardiography over the two-dimensional technique in the assessment of aortic atherosclerotic thrombi and ulcers.

PubMed

Elsayed, Mahmoud; Bulur, Serkan; Kalla, Aditi; Ahmed, Mustafa I; Hsiung, Ming C; Uygur, Begum; Alagic, Nermina; Sungur, Aylin; Singh, Satinder; Nanda, Navin C

2016-08-01

We present two cases in whom live/real time three-dimensional transesophageal echocardiography (3DTEE) provided incremental value in the assessment of atherosclerotic disease in the aorta. In one patient, it identified additional atherosclerotic ulcers as well as thrombi within them which were missed by two-dimensional (2D) TEE. In both cases, the size of the large mobile atherosclerotic plaque was underestimated by 2DTEE as compared with 3DTEE. Furthermore, 3DTEE provided volume quantification of the thrombi and ulcers which is not possible by 2DTEE. The echocardiographic findings of atherosclerotic plaques were confirmed by computed tomography in one patient and by surgery in the other. © 2016, Wiley Periodicals, Inc.

Use of the Coelomic Grafting Technique for Prolonged ex utero Cultivation of Late Preprimitive Streak-Stage Rabbit Embryos.

PubMed

Püschel, Bernd; Männer, Jörg

2016-01-01

Due to its morphological similarity with the early human embryo, the pregastrulation-stage rabbit may represent an appropriate mammalian model for studying processes involved in early human development. The usability of mammalian embryos for experimental studies depends on the availability of whole embryo culture methods facilitating prolonged ex utero development. While currently used culture methods yield high success rates for embryos from primitive streak stages onward, the success rate of extended cultivation of preprimitive streak-stage mammalian embryos is low for all previously established methods and for all studied species. This limits the usability of preprimitive streak-stage rabbit embryos in experimental embryology. We have tested whether the extraembryonic coelom of 4-day-old chick embryos may be used for prolonged ex utero culture of preprimitive streak-stage rabbit embryos (stage 2, 6.2 days post coitum). We found that, within this environment, stage 2 rabbit blastocysts can be cultured at decreasing success rates (55% after 1 day, 35% after 2 days, 15% after 3 days) up to a maximum of 72 h. Grafted blastocysts can continue development from the onset of gastrulation to early organogenesis and thereby form all structures characterizing age-matched controls (e.g. neural tube, somites, beating heart). Compared to normal controls, successfully cultured embryos developed at a slower rate and finally showed some structural and gross morphological anomalies. The method presented here was originally developed for whole embryo culture of mouse embryos by Gluecksohn-Schoenheimer in 1941. It is a simple and inexpensive method that may represent a useful extension to presently available ex utero culture systems for rabbit embryos. © 2016 S. Karger AG, Basel.

Cystoscopic diagnosis of polypoid cystitis in two pet rabbits.

PubMed

Di Girolamo, Nicola; Bongiovanni, Laura; Ferro, Silvia; Melidone, Raffaele; Nicoletti, Annalisa; Duca, Valeria Del; Donnelly, Thomas M; Selleri, Paolo

2017-07-01

CASE DESCRIPTION AS-year-old male Dwarf rabbit and 4-year-old female Mini-Rex rabbit were evaluated because of anorexia and urine scalding of the perineum. CLINICAL FINDINGS Abdominal radiography revealed a diffuse increase in the opacity of the urinary bladder attributable to urinary sludge. In 1 rabbit, abdominal ultrasonography revealed several mass-like lesions protruding from the mucosal surface into the lumen of the urinary bladder. Rabbits were anesthetized, and cystoscopy was performed with a rigid 2.7-mm, 30° endoscope. Histologic analysis of tissue samples obtained through the cystoscope operating channel revealed findings consistent with polypoid cystitis. TREATMENT AND OUTCOME To remove the urinary sludge from each rabbit, the urinary bladder was filled with sterile saline (0.9% NaCl) solution and emptied with a gentle massage several times until the ejected fluid was transparent. Rabbits were treated with NSAIDs, antimicrobials (chosen following microbial culture of urine and antimicrobial susceptibility testing), bathing of the perineum, and a low-calcium diet. The male rabbit died of unrelated causes 18 months later; postmortem examination findings confirmed the polypoid cystitis. The female rabbit remained disease free through to last follow-up (12 months after initial evaluation). CLINICAL RELEVANCE This was the first report of polypoid cystitis in pet rabbits. Although ultrasonographic findings supported this diagnosis, a definitive diagnosis was achieved through cystoscopy and lesion biopsy. Treatments administered were intended to reduce the potential sources of irritation. Research is needed to investigate the effectiveness of the applied interventions and the association between excessive urinary calcium excretion and polyploid cystitis in rabbits.

Anaemia in pet rabbits: causes, severity and reticulocyte response.

PubMed

Dettweiler, Alexandra; Klopfleisch, Robert; Müller, Kerstin

2017-12-16

The objective of the study was to determine the causes and the severity of anaemia in pet rabbits ( Oryctolagus cuniculus ), to classify anaemia and to compare the reticulocyte counts from healthy and anaemic rabbits. Over a time period of 11 years (2000-2011) a retrospective and prospective study of 223 pet rabbits was performed. Based on the clinic's own reference range for healthy pet rabbits (packed cell volume [PCV] levels 0.33-0.45 l/l), animals with a PCV level below 0.33 l/l were considered anaemic. Anaemia was mostly caused by inflammation (65/223, 29 per cent) and bleeding (54/223, 24 per cent). Seven per cent (15/223) of the rabbits suffered from renal diseases and one rabbit got diagnosed with haemolysis caused by liver lobe torsion. In 14 per cent (32/223) of the rabbits more than one underlying pathomechanism, like inflammation and bleeding, was diagnosed as possible cause of anaemia. In 25 per cent (56/223) of the anaemic rabbits no cause was found. Most anaemias were mild (156/223, 70 per cent). Moderate (43/223, 19 per cent) or severe (24/223, 11 per cent) anaemia was diagnosed more rarely. Anaemic rabbits showed similar reticulocyte counts to healthy rabbits with no significant difference. Therefore, a differentiation of regenerative and non-regenerative anaemia was not possible. © British Veterinary Association (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Pygmy rabbit surveys on state lands in Oregon

USGS Publications Warehouse

Hagar, Joan; Lienkaemper, George

2007-01-01

The pygmy rabbit (Brachylagus idahoensis) is classified by the federal government as a species of concern (i.e., under review by the U.S. Fish and Wildlife Service for consideration as a candidate for listing as threatened or endangered under the Endangered Species Act) because of its specialized habitat requirements and evidence of declining populations. The Oregon Department of Fish and Wildlife (ODFW) lists pygmy rabbits as “sensitive-vulnerable,” meaning that protective measures are needed if sustainable populations are to be maintained over time (Oregon Natural Heritage Program, 2001). The Oregon Natural Heritage Program considers this species to be threatened with extirpation from Oregon. Pygmy rabbits also are a species of concern in all the other states where they occur (NatureServe, 2004). The Washington population, known as the Columbia Basin pygmy rabbit, was listed as endangered by the federal government in 2003. Historically, pygmy rabbits have been collected from Deschutes, Klamath, Crook, Lake, Grant, Harney, Baker, and Malheur Counties in Oregon. However, the geographic range of pygmy rabbit in Oregon may have decreased in historic times (Verts and Carraway, 1998), and boundaries of the current distribution are not known. Not all potentially suitable sites appear to be occupied, and populations are susceptible to rapid declines and local extirpation (Weiss and Verts, 1984). In order to protect and manage remaining populations on State of Oregon lands, Oregon Department of Fish and Wildlife needs to identify areas currently occupied by pygmy rabbits, as well as suitable habitats. The main objective of this survey was document to presence or absence of pygmy rabbits on state lands in Malheur, Harney, Lake, and Deschutes counties. Knowledge of the location and extent of pygmy rabbit populations can provide a foundation for the conservation and management of this species in Oregon. The pygmy rabbit is just one of a suite of species of concern

Deficiency of Cholesteryl Ester Transfer Protein Protects Against Atherosclerosis in Rabbits.

PubMed

Zhang, Jifeng; Niimi, Manabu; Yang, Dongshan; Liang, Jingyan; Xu, Jie; Kimura, Tokuhide; Mathew, Anna V; Guo, Yanhong; Fan, Yanbo; Zhu, Tianqing; Song, Jun; Ackermann, Rose; Koike, Yui; Schwendeman, Anna; Lai, Liangxue; Pennathur, Subramaniam; Garcia-Barrio, Minerva; Fan, Jianglin; Chen, Y Eugene

2017-06-01

CETP (cholesteryl ester transfer protein) plays an important role in lipoprotein metabolism; however, whether inhibition of CETP activity can prevent cardiovascular disease remains controversial. We generated CETP knockout (KO) rabbits by zinc finger nuclease gene editing and compared their susceptibility to cholesterol diet-induced atherosclerosis to that of wild-type (WT) rabbits. On a chow diet, KO rabbits showed higher plasma levels of high-density lipoprotein (HDL) cholesterol than WT controls, and HDL particles of KO rabbits were essentially rich in apolipoprotein AI and apolipoprotein E contents. When challenged with a cholesterol-rich diet for 18 weeks, KO rabbits not only had higher HDL cholesterol levels but also lower total cholesterol levels than WT rabbits. Analysis of plasma lipoproteins revealed that reduced plasma total cholesterol in KO rabbits was attributable to decreased apolipoprotein B-containing particles, while HDLs remained higher than that in WT rabbits. Both aortic and coronary atherosclerosis was significantly reduced in KO rabbits compared with WT rabbits. Apolipoprotein B-depleted plasma isolated from CETP KO rabbits showed significantly higher capacity for cholesterol efflux from macrophages than that from WT rabbits. Furthermore, HDLs isolated from CETP KO rabbits suppressed tumor necrosis factor-α-induced vascular cell adhesion molecule 1 and E-selectin expression in cultured endothelial cells. These results provide evidence that genetic ablation of CETP activity protects against cholesterol diet-induced atherosclerosis in rabbits. © 2017 American Heart Association, Inc.

Myxomatosis in farmland rabbit populations in England and Wales.

PubMed

Ross, J; Tittensor, A M; Fox, A P; Sanders, M F

1989-10-01

The overall pattern and consequences of myxomatosis in wild rabbit populations were studied at three farmland sites in lowland southern England and upland central Wales between 1971 and 1978. When results from all years were combined, the disease showed a clear two-peaked annual cycle, with a main autumn peak between August and January, and a subsidiary spring peak during February to April. Rabbit fleas, the main vectors of myxomatosis in Britain, were present on full-grown rabbits in sufficient numbers for transmission to occur throughout the year, but the observed seasonal pattern of the disease appeared to be influenced by seasonal mass movements of these fleas. However other factors were also important including the timing and success of the main rabbit breeding season, the proportion of rabbits which had recovered from the disease and the timing and extent of autumn rabbit mortality from other causes. Significantly more males than females, and more adults and immatures than juveniles, were observed to be infected by myxomatosis. Only 25-27% of the total populations were seen to be infected during outbreaks. Using two independent methods of calculation, it was estimated that between 47 and 69% of infected rabbits died from the disease (much lower than the expected 90-95% for fully susceptible rabbits with the partly attenuated virus strains that predominated). Thus it was estimated that 12-19% of the total rabbit populations were known to have died directly or indirectly from myxomatosis. Although the effects of myxomatosis were much less than during the 1950s and 1960s, it continued to be an important mortality factor. It may still have a regulatory effect on rabbit numbers, with autumn/winter peaks of disease reducing the numbers of rabbits present at the start of the breeding season.

Myxomatosis in farmland rabbit populations in England and Wales.

PubMed Central

Ross, J.; Tittensor, A. M.; Fox, A. P.; Sanders, M. F.

1989-01-01

The overall pattern and consequences of myxomatosis in wild rabbit populations were studied at three farmland sites in lowland southern England and upland central Wales between 1971 and 1978. When results from all years were combined, the disease showed a clear two-peaked annual cycle, with a main autumn peak between August and January, and a subsidiary spring peak during February to April. Rabbit fleas, the main vectors of myxomatosis in Britain, were present on full-grown rabbits in sufficient numbers for transmission to occur throughout the year, but the observed seasonal pattern of the disease appeared to be influenced by seasonal mass movements of these fleas. However other factors were also important including the timing and success of the main rabbit breeding season, the proportion of rabbits which had recovered from the disease and the timing and extent of autumn rabbit mortality from other causes. Significantly more males than females, and more adults and immatures than juveniles, were observed to be infected by myxomatosis. Only 25-27% of the total populations were seen to be infected during outbreaks. Using two independent methods of calculation, it was estimated that between 47 and 69% of infected rabbits died from the disease (much lower than the expected 90-95% for fully susceptible rabbits with the partly attenuated virus strains that predominated). Thus it was estimated that 12-19% of the total rabbit populations were known to have died directly or indirectly from myxomatosis. Although the effects of myxomatosis were much less than during the 1950s and 1960s, it continued to be an important mortality factor. It may still have a regulatory effect on rabbit numbers, with autumn/winter peaks of disease reducing the numbers of rabbits present at the start of the breeding season. PMID:2806418

Rabbits and men: relating their ages.

PubMed

Dutta, Sulagna; Sengupta, Pallav

2018-04-19

Rabbit, a member of the Lagomorpha order, is the closest phylogenetic relative to humans, next to primates. It possesses greater acceptability as a laboratory mammal than primates in terms of husbandry, breeding ease, cost effectiveness, and legal ethical conveniences. Moreover, as a laboratory animal, the rabbit also owns its advantages over mice or rats, in terms of phylogenetic resemblance to human, size, blood volume, responsiveness, and other congruences enabling them to better imitate human physiological characteristics in biomedical research. A specific research aspires to effectuate its outcome on a particular human age group, for which it is pivotal to select a laboratory rabbit of exact age, which will correlate with that specific age of a human, which is currently based on mere approximation. This article is the first ever scientific venture, focused to swap this approximation of laboratory rabbit age with accuracy by relating it with that of humans analyzing different phases of life individually. Considering the diminutive lifespan of rabbits compared to humans, the correlation of their age with respect to the entire lifespan, which we found out to be 45.625 days compared to one human year, is not enough. Thereby, like our previous articles that formulated concise relation of age of laboratory rats and mice with human age, in this article also, we aim to aid biomedical research specificity in the selection of laboratory model age, separately correlating different life phases of humans with that of rabbits, the second mostly used mammal in 2016 in the United States.

Cardiovascular physiology and diseases of the rabbit.

PubMed

Pariaut, Romain

2009-01-01

This article reviews what is known about the diagnosis and management of cardiovascular diseases in the pet rabbit. Current knowledge is based on anecdotal reports, derived from research data using the rabbit as an animal model of human cardiovascular diseases, but most importantly canine and feline cardiology. It is likely that, as cardiovascular diseases are more often recognized, more specific information will soon become available for the treatment of the pet rabbit with cardiac disease.

Histomorphometric examination of long-term changes in temporomandibular joints after mandibular lengthening by distraction osteogenesis in rabbits.

PubMed

Mihmanli, Ahmet; Dolanmaz, Doğan; Tüz, Hakan; Pampu, Alper; Dönmez, Hasan Hüseyin

2012-05-01

The purpose of this study was to evaluate long-term histomorphometric changes in temporomandibular joints (TMJs) of rabbits after mandibular distraction osteogenesis (DO). Twenty-six rabbits were used in this study. Two of them served as control subjects, and the remaining 24 underwent DO procedures in their left mandibular bodies. After a latency period of 5 days, 5 mm lengthening was performed at a rate of 1 mm/d. The rabbits in the experimental group were randomly divided into 4 subgroups and killed after 1, 2, 4, and 6 months. TMJs from both sides were harvested and prepared with hematoxylin and eosin stain for histomorphometric examination under an optical microscope. Compared with control subjects and nondistracted sides, fibrous articular, proliferative, and hypertrophic areas were significantly increased (P < .05) in the first 2 months in distracted sides. The changes were insignificant in the fourth and sixth postoperative months. Unilateral mandibular distraction of 5 mm was found to be well tolerated and no degenerative changes were observed histologically in the rabbit TMJs in the long-term period. Copyright © 2012 Elsevier Inc. All rights reserved.

αVβ3 integrin-targeted microSPECT/CT imaging of inflamed atherosclerotic plaques in mice.

PubMed

Vancraeynest, David; Roelants, Véronique; Bouzin, Caroline; Hanin, François-Xavier; Walrand, Stephan; Bol, Vanesa; Bol, Anne; Pouleur, Anne-Catherine; Pasquet, Agnès; Gerber, Bernhard; Lesnik, Philippe; Huby, Thierry; Jamar, François; Vanoverschelde, Jean-Louis

2016-12-01

αVβ3-integrin is expressed by activated endothelial cells and macrophages in atherosclerotic plaques and may represent a valuable marker of high-risk plaques. We evaluated (99m)Tc-maraciclatide, an integrin-specific tracer, for imaging vascular inflammation in atherosclerotic lesions in mice. Apolipoprotein E-negative (ApoE(-/-)) mice on a Western diet (n = 10) and normally fed adult C57BL/6 control mice (n = 4) were injected with (99m)Tc-maraciclatide (51.8 ± 3.7 MBq). A blocking peptide was infused in three ApoE(-/-) mice; this condition served as another control. After 90 min, the animals were imaged via single-photon emission computed tomography (SPECT). While maintained in the same position, the mice were transferred to computed tomography (CT) to obtain contrast-enhanced images of the aortic arch. Images from both modalities were fused, and signal was quantified in the aortic arch and in the vena cava for subtraction of blood-pool activity. The aorta was carefully dissected after imaging for gamma counting, autoradiography, and histology. Tracer uptake was significantly higher in ApoE(-/-) mice than in both groups of control mice (1.56 ± 0.33 vs. 0.82 ± 0.24 vs. 0.98 ± 0.11, respectively; P = 0.006). Furthermore, higher tracer activity was detected via gamma counting in the aorta of hypercholesterolemic mice than in both groups of control mice (1.52 ± 0.43 vs. 0.78 ± 0.19 vs. 0.47 ± 0.31 (99m)Tc-maraciclatide %ID/g, respectively; P = 0.018). Autoradiography showed significantly higher tracer uptake in the atherosclerotic aorta than in the control aorta (P = 0.026). Finally, in the atherosclerotic aorta, immunostaining indicated that the integrin signal came predominantly from macrophages and was correlated with the macrophage CD68 immunomarker (r = 0.73). (99m)Tc-maraciclatide allows in vivo detection of inflamed atherosclerotic plaques in mice and may represent a non-invasive approach for

Effects of rigid fixation on the growing neurocranium of immature rabbits.

PubMed

Sanus, Galip Zihni; Tanriverdi, Taner; Kacira, Tibet; Jackson, Ian T

2007-03-01

The improved intraoperative long-term skeletal stability achieved with rigid fixation techniques has led to their widespread popularity and application. However, experimental studies have revealed some drawbacks related to metallic implants and long-term results of clinical studies, especially in pediatric patients, has confirmed the results of experimental studies. Our aim in this experimental study using an infant rabbit model is to answer the following question: "Does short-term skeletal stability cause long-term growth inhibition?" Forty, 9-day-old New Zealand white albino rabbits were divided into four groups: 1) experimental, n=6: plated across the right coronal suture and two screws on each side of the left coronal suture; 2) re-operation, n=6: the same materials as group I were placed, and only the plate was removed at the end of 1 month; 3) sham, n=6: sham control with simulated surgery and two screws on each side of the left coronal suture; 4) control, n=2: no operation. The animals were killed 6 months after microplate application, and the skulls were evaluated both grossly and cephalometrically. Gross examination showed that the plates and the screws were covered by bony overgrowth and caused bony irregularity and regional bone degeneration. The parietal bones on the plated sides became striated and lost their concave shape. Cephalometric analysis demonstrated overt mastoid tip deviation toward, or shortening of cranionasal length on, the side with rigid fixation. We conclude from our study that rigid fixation during skeletal development causes growth retardation and should not be used in the growing child.

Haloperidol inhibits the development of atherosclerotic lesions in LDL receptor knockout mice.

PubMed

van der Sluis, Ronald J; Nahon, Joya E; Reuwer, Anne Q; Van Eck, Miranda; Hoekstra, Menno

2015-05-01

Antipsychotic drugs have been shown to modulate the expression of ATP-binding cassette transporter A1 (ABCA1), a key factor in the anti-atherogenic reverse cholesterol transport process, in vitro. Here we evaluated the potential of the typical antipsychotic drug haloperidol to modulate the cholesterol efflux function of macrophages in vitro and their susceptibility to atherosclerosis in vivo. Thioglycollate-elicited peritoneal macrophages were used for in vitro studies. Hyperlipidaemic low-density lipoprotein (LDL) receptor knockout mice were implanted with a haloperidol-containing pellet and subsequently fed a Western-type diet for 5 weeks to induce the development of atherosclerotic lesions in vivo. Haloperidol induced a 54% decrease in the mRNA expression of ABCA1 in peritoneal macrophages. This coincided with a 30% decrease in the capacity of macrophages to efflux cholesterol to apolipoprotein A1. Haloperidol treatment stimulated the expression of ABCA1 (+51%) and other genes involved in reverse cholesterol transport, that is, CYP7A1 (+98%) in livers of LDL receptor knockout mice. No change in splenic ABCA1 expression was noted. However, the average size of the atherosclerotic size was significantly smaller (-31%) in the context of a mildly more atherogenic metabolic phenotype upon haloperidol treatment. More importantly, haloperidol markedly lowered MCP-1 expression (-70%) and secretion (-28%) by peritoneal macrophages. Haloperidol treatment lowered the susceptibility of hyperlipidaemic LDL receptor knockout mice to develop atherosclerotic lesions. Our findings suggest that the beneficial effect of haloperidol on atherosclerosis susceptibility can be attributed to its ability to inhibit macrophage chemotaxis. © 2015 The British Pharmacological Society.

Reduced Intimal Hyperplasia in Rabbits via Medical Therapy after Carotid Venous Bypass

PubMed Central

Yucel, Semih; Bahcivan, Muzaffer; Gol, Mehmet Kamil; Erenler, Behice H.; Kolbakir, Fersat; Keceligil, Hasan T.

2009-01-01

Intimal hyperplasia is a major cause of restenosis after the interventional or surgical treatment of occlusive arterial disease. We investigated the effects of clopidogrel, calcium dobesilate, nebivolol, and atorvastatin on the development of intimal hyperplasia in rabbits after carotid venous bypass surgery. We divided 40 male New Zealand rabbits into 4 study groups and 1 control group. After occluding the carotid arteries of the rabbits, we constructed jugular venous grafts between the proximal and the distal segments of the occluded artery. Thereafter, group 1 (control) received no medication. We administered daily oral doses of clopidogrel to group 2, calcium dobesilate to group 3, nebivolol to group 4, and atorvastatin to group 5. The rabbits were killed 28 days postoperatively. The arterialized jugular venous grafts were extracted for histopathologic examination. Intimal thicknesses were 42.87 ± 6.95 μm (group 2), 46.5 ± 9.02 μm (group 3), 34.12 ± 5.64 μm (group 4), and 48.37 ± 6.16 μm (group 5), all significantly less than the 95.12 ± 9.93 μm in group 1 (all P < 0.001). Medial thicknesses were 94 ± 6 μm (group 2), 101.5 ± 13.52 μm (group 3), 90.5 ± 9.69 μm (group 4), and 101.37 ± 7.99 μm (group 5), all significantly thinner than the 126.62 ± 13.53 μm in group 1 (all P < 0.001). In our experimental model of carotid venous bypass grafting in rabbits, clopidogrel, calcium dobesilate, nebivolol, and atorvastatin each effectively reduced the development of intimal hyperplasia. Herein, we discuss our findings and review the medical literature. PMID:19876413

A fluorescence lifetime spectroscopy study of matrix metalloproteinases -2 and -9 in human atherosclerotic plaque

PubMed Central

Phipps, Jennifer E.; Hatami, Nisa; Galis, Zorina S.; Baker, J. Dennis; Fishbein, Michael C.; Marcu, Laura

2011-01-01

Matrix metalloproteinase (MMP) -2 and -9 play important roles in the progression of atherosclerosis. This study aims to determine whether MMP-2 and -9 content in the fibrotic caps of atherosclerotic plaque is correlated with plaque autofluorescence. A time-resolved laser-induced fluorescence spectroscopy (TR-LIFS) system was used to measure the autofluorescence and assess the biochemical composition of human plaques obtained from carotid endarterectomy. Results presented here demonstrate for the first time the ability to characterize the biochemical composition as it relates to MMP-2 and -9 content in the atherosclerotic plaque cap using a label-free imaging technique implemented with a fiberoptic TR-LIFS system. PMID:21770037

Effects of silibinin hemisuccinate on the intraocular pressure in normotensive rabbits.

PubMed

Mohammed, Haider M; Abdulrazzaq, Munaf H; Hussain, Saad A

2007-09-01

To evaluate the effects of silibinin hemisuccinate on the normal intraocular pressure (IOP) in rabbits. This study took place in the Department of Pharmacology and Toxicology, College of Pharmacy, University of Baghdad during the period from January to June 2005. Twenty-five New Zealand white rabbits weighing 1.5-2.5 kg were used in this study. The effects of corneal instillation of various concentrations of silibinin hemisuccinate (0.5%, 0.75% and 1%) dissolved in arachis oil, on the normal intraocular pressure in rabbits were evaluated using indentation tonometry; in addition to the possible modulation of normal IOP-recovery time after intravenous infusion of 20% sodium chloride solution. The results showed that within 30 minutes of application, silibinin in various concentrations significantly reduces IOP in comparison to baseline values (p<0.05), with greater reduction being achieved with 0.75%. The effect of IOP reduction lasts 2-3 hours and proportionate to the concentration used. Moreover, remarkable delay in IOP recovery was observed after instillation of silibinin compared with the vehicle treated (arachis oil) animals, indicating interference with aqueous humor formation. The results obtained in this study provide experimental evidences for the effectiveness of silibinin in the reduction of IOP and possible modulation of its regulatory mechanisms.

Anti-Inflammatory and Antioxidative Stress Effects of Oryzanol in Glaucomatous Rabbits.

PubMed

Panchal, Shital S; Patidar, Rajesh K; Jha, Abhishek B; Allam, Ahmed A; Ajarem, Jamaan; Butani, Shital B

2017-01-01

Purpose . γ -Oryzanol works by anti-inflammatory and radical scavenging activity as a neuroprotective, anticancer, antiulcer, and immunosuppressive agent. The present study was conducted to investigate effect of oryzanol in acute and chronic experimental glaucoma in rabbits. Methods . Effect of oryzanol was evaluated in 5% dextrose induced acute model of ocular hypertension in rabbit eye. Chronic model of glaucoma was induced with subconjunctival injection of 5% of 0.3 ml phenol. Treatment with oryzanol was given for next two weeks after induction of glaucoma. From anterior chamber of rabbit eye aqueous humor was collected to assess various oxidative stress parameters like malondialdehyde, superoxide dismutase, glutathione peroxidase, catalase, nitric oxide, and inflammatory parameters like TNF- α and IL-6. Structural damage in eye was examined by histopathological studies. Results . In acute model of ocular hypertension oryzanol did not alter raised intraocular pressure. In chronic model of glaucoma oryzanol exhibited significant reduction in oxidative stress followed by reduction in intraocular pressure. Oryzanol treatment reduced level of TNF- α and IL-6. Histopathological studies revealed decreased structural damage of trabecular meshwork, lamina cribrosa, and retina with oryzanol treatment. Conclusions . Oryzanol showed protective effect against glaucoma by its antioxidative stress and anti-inflammatory property. Treatment with oryzanol can reduce optic nerve damage.

Regression of atherosclerosis with apple procyanidins by activating the ATP-binding cassette subfamily A member 1 in a rabbit model.

PubMed

Wang, Liang; Fumoto, Toshio; Masumoto, Saeko; Shoji, Toshihiko; Miura, Tomisato; Naraoka, Masato; Matsuda, Naoya; Imaizumi, Tadaatsu; Ohkuma, Hiroki

2017-03-01

Apple polyphenol contains abundant procyanidins, which have been associated with an anti-atherosclerosis and cholesterol-lowering effect. The aim of this study was to investigate whether apple procyanidins (APCs) feature therapeutic efficacy in terms of regressing atherosclerosis and whether this efficacy is due to mechanisms other than a cholesterol-lowering effect. After eight weeks on an atherogenic diet, rabbits were given a normal diet for another eight weeks to normalize the increased serum lipids level. The rabbits in the baseline group were sacrificed at this stage. The control group was subsequently fed a normal diet for eight weeks, while the APCs group was administrated 50 mg/kg/day of APCs in addition to the normal diet. Serum lipids and aortic intimal-medial thickness (IMT) were serially examined, and the resected aorta was examined histologically and through molecular biology. Aortic IMT on ultrasonography and the lipid accumulation area examined using Sudan IV staining were significantly reduced in the APCs group as compared to the control group. Serum lipid profiles were not different between the groups. Immunohistochemistry showed significantly decreased staining of an oxidative stress marker and significantly increased staining of ATP-binding cassette subfamily A member 1 (ABCA1) in the APCs group. Western blotting and RT-PCR also showed increased expression of ABCA1 mRNA and its protein in the APCs group. This study revealed that APCs administration causes a regression of atherosclerosis. APCs might hold promise as an anti-atherosclerotic agent. Copyright © 2017 Elsevier B.V. All rights reserved.

Eyeblink conditioning in the developing rabbit

PubMed Central

Brown, Kevin L.; Woodruff-Pak, Diana S.

2011-01-01

Eyeblink classical conditioning in pre-weanling rabbits was examined in the present study. Using a custom lightweight headpiece and restrainer, New Zealand white littermates were trained once daily in 400 ms delay eyeblink classical conditioning from postnatal days (PD) 17–21 or PD 24–28. These ages were chosen because eyeblink conditioning emerges gradually over PD 17–24 in rats (Stanton, Freeman, & Skelton, 1992), another altricial species with neurodevelopmental features similar to those of rabbits. Consistent with well-established findings in rats, rabbits trained from PD 24–28 showed greater conditioning relative to littermates trained from PD 17–21. Both age groups displayed poor retention of eyeblink conditioning at retraining one month after acquisition. These findings are the first to demonstrate eyeblink conditioning in the developing rabbit. With further characterization of optimal conditioning parameters, this preparation may have applications to neurodevelopmental disease models as well as research exploring the ontogeny of memory. PMID:21953433

Gonadal and extra-gonadal sperm reserves and sperm production of pubertal rabbits fed dietary fumonisin B1.

PubMed

Ewuola, E O; Egbunike, G N

2010-06-01

The influence of fumonisin B(1) (a mycotoxin produced by Fusarium verticillioides) on sperm reserves and production of crossbred pubertal rabbits was studied using an experimental model that lasted 28 weeks. Forty-eight male rabbits, 7 weeks old and with average weight of 757.50+/-0.50 g, were allotted to four dietary fumonisin B(1) concentrations of 0.13, 5.0, 7.5 and 10.0 mg kg(-1) constituting diets 1 (control), 2, 3 and 4, respectively. The paired testes weight of rabbits fed diet 3 was significantly (P<0.05) higher than those fed diet 2 and the control. However, the epididymal weight was significantly (P<0.05) lower in rabbits fed the control diet as compared to others on test diets. The gonadal sperm reserves of the animals were significantly (P<0.05) reduced by the toxin with increased concentrations of the toxin in the diets. The sperm reserves per testis and per gram testis were significantly (P<0.05) higher in the control rabbits than those fed diets 3 and 4. The sperm reserves in caput, corpus and caudal epididymis declined significantly with each increase in the fumonisin concentration in the diets. The number of spermatozoa in total caput, corpus and cauda was significantly (P<0.05) higher in rabbits fed the control diet and the least in rabbits fed diet 4 containing 10.0mg fumonisin B(1)/kg. Extra-gonadal sperm reserves significantly decreased (P<0.05) in rabbits fed diets 3 and 4 compared to the control. The daily sperm production of the animals fed diets 2, 3 and 4 declined significantly to 67, 59 and 36% relative to those animals fed the control diet. This study suggests that exposure of breeding male rabbits to diets contaminated with fumonisin B(1) up to 7.5 mg fumonisin B(1)/kg will depress testicular and epididymal sperm reserves and sperm production and potentially impair reproduction in the animals. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Effects of myxoma virus and rabbit hemorrhagic disease virus on the physiological condition of wild European rabbits: Is blood biochemistry a useful monitoring tool?

PubMed

Pacios-Palma, Isabel; Santoro, Simone; Bertó-Moran, Alejandro; Moreno, Sacramento; Rouco, Carlos

2016-12-01

Myxomatosis and rabbit hemorrhagic disease (RHD) are the major viral diseases that affect the wild European rabbit (Oryctolagus cuniculus). These diseases arrived in Europe within the last decades and have caused wild rabbit populations to decline dramatically. Both viruses are currently considered to be endemic in the Iberian Peninsula; periodic outbreaks that strongly impact wild populations regularly occur. Myxoma virus (MV) and rabbit hemorrhagic disease virus (RHDV) alter the physiology of infected rabbits, resulting in physical deterioration. Consequently, the persistence and viability of natural populations are affected. The main goal of our study was to determine if blood biochemistry is correlated with serostatus in wild European rabbits. We carried out seven live-trapping sessions in three wild rabbit populations over a two-year period. Blood samples were collected to measure anti-MV and anti-RHDV antibody concentrations and to measure biochemical parameters related to organ function, protein metabolism, and nutritional status. Overall, we found no significant relationships between rabbit serostatus and biochemistry. Our main result was that rabbits that were seropositive for both MV and RHDV had low gamma glutamyltransferase concentrations. Given the robustness of our analyses, the lack of significant relationships may indicate that the biochemical parameters measured are poor proxies for serostatus. Another explanation is that wild rabbits might be producing attenuated physiological responses to these viruses because the latter are now enzootic in the study area. Copyright © 2016 Elsevier Ltd. All rights reserved.

+Gz-induced post-cholecystectomy syndrome in rabbit model by using a telemetric method

PubMed Central

Kong, Yalin; Zhao, Gang; Li, Yifeng; Wen, Dongqing; Zhang, Hui; He, Xiaojun; Zhen, Yuying; Zhang, Hongyi

2015-01-01

Aviation-related mechanism may exist in the post-cholecystectomy syndrome (PCS) of aircrew patients. The aim of this study was to test this hypothesis on vivo rabbit model and to explore the mechanism by using a novel telemetric method. We constructed a bile duct-to-intestinal bridge bypass on 30 rabbits, with a telemetry implant attached to the Oddi’s sphincter. Then a telemetric recording system was used to record the biliary pressure fluctuation through the subcutaneous bridge and the changes of electromyography of the Oddi’s sphincter under different +Gz acceleration. Self-control comparison was made before and after cholecystectomy. The fully implantable device was very well accepted by rabbits and the data could reflect the real experimental environment simultaneously. Biliary pressure in common bile duct increased accordingly with +Gz acceleration increased, but bile secretion didn’t change. Although +Gz acceleration could increase the frequency of burst of spike potentials in the Oddi’s sphincter, the frequency didn’t change with the +Gz acceleration increased, and the spike activity didn’t change obviously before cholecystectomy. After cholecystectomy, the biliary pressure in common bile duct remained high in 12 rabbits (40%) under +Gz exposure, and the pressure value didn’t change as the +Gz acceleration increased. The long-time changes in electromyography of the Oddi’s sphincter were observed in the same 12 rabbits, with symptoms of PCS developed in 9 of them. +Gz exposure is an important external factor leading to the biliary physiology disorder, and it may induce PCS in some aircrew patients with individual susceptibility, which means gallbladder maybe a dominant factor in regulating the biliary physiology in theses aircrew patients. PMID:26064268

Effects of irradiation combined with cis-diamminedichloroplatinum (CDDP) suppository in rabbit VX2 rectal tumors.

PubMed

Wakatsuki, Kazuo; Oda, Kenji; Koda, Keiji; Seike, Kazuhiro; Takiguchi, Nobuhiro; Saito, Norio; Miyazaki, Masaru

2005-03-01

To decrease local recurrence and increase disease free survival, various preoperative therapies for patients with advanced rectal cancer have been studied. Cis-diamminedichloroplatinum (II) (CDDP) has become one of the most widely used cancer chemotherapeutic drugs. It has also been found to have radiosensitizing properties. In this experimental study, the efficacy of chemoradiotherapy using a novel CDDP suppository, and one with mixed micelles, was examined in a rabbit VX2 rectal tumor model. Rabbits were divided into four groups: control group, irradiation (R) group, CDDP suppository plus irradiation (CR) group, and mixed micelles plus CDDP suppository plus irradiation (CMR) group. Tumor growth ratios were reduced significantly in the CR and CMR groups as compared with the ratio in the control group. Microscopically, response rates of main tumors were 0%, 33.3%, 70.0%, and 91. 7%, respectively. The number of metastatic lymph nodes in the CR and CMR groups decreased significantly compared to the control group and the R group. The microscopic response rates of metastatic lymph nodes were 0%, 11.1%, 40.0%, and 41.7%, respectively. Lung metastases were observed in three rabbits in the R group, and in one rabbit in the CMR group. Tissue platinum concentrations both in tumors and in regional lymph nodes increased significantly when mixed micelles were used. Chemoradiotherapy using the CDDP suppository and mixed micelles was effective for local control in the rabbit VX2 rectal tumor model.

A single immunization with a dry powder anthrax vaccine protects rabbits against lethal aerosol challenge

PubMed Central

Klas, S.D.; Petrie, C.R.; Warwood, S.J.; Williams, M.S.; Olds, C.L.; Stenz, J.P.; Cheff, A.M.; Hinchcliffe, M.; Richardson, C.; Wimer, S.

2009-01-01

Here we confirm that intranasal (IN) dry powder anthrax vaccine formulations are able to protect rabbits against aerosol challenge 9 weeks after a single immunization. The optimum dose of rPA in our dry powder anthrax vaccine formulation in rabbits was experimentally determined to be 150 μg and therefore was chosen as the target dose for all subsequent experiments. Rabbits received a single dose of either 150 μg rPA, 150 μg rPA + 150 μg of a conjugated 10-mer peptide representing the B. anthracis capsule (conj), or 150 μg of conj alone. All dry powder formulations contained MPL and chitosan (ChiSys®). Significant anti-rPA titers and anthrax lethal toxin neutralizing antibody (TNA) levels were seen with both rPA containing vaccines, although rPA-specific IgG and TNA levels were reduced in rabbits immunized with rPA plus conj. Nine weeks after immunization, rabbits were exposed to a mean aerosol challenge dose of 278 LD50 of Ames spores. Groups immunized with rPA or with rPA + conj had significant increases in survivor proportions compared to the negative control group by Logrank test (p = 0.0001 and 0.003, respectively), and survival was not statistically different for the rPA and rPA + conj immunized groups (p = 0.63). These data demonstrate that a single immunization with our dry powder anthrax vaccine can protect against a lethal aerosol spore challenge 9 weeks later. PMID:18703110

A single immunization with a dry powder anthrax vaccine protects rabbits against lethal aerosol challenge.

PubMed

Klas, S D; Petrie, C R; Warwood, S J; Williams, M S; Olds, C L; Stenz, J P; Cheff, A M; Hinchcliffe, M; Richardson, C; Wimer, S

2008-10-09

Here we confirm that intranasal (IN) dry powder anthrax vaccine formulations are able to protect rabbits against aerosol challenge 9 weeks after a single immunization. The optimum dose of rPA in our dry powder anthrax vaccine formulation in rabbits was experimentally determined to be 150microg and therefore was chosen as the target dose for all subsequent experiments. Rabbits received a single dose of either 150microg rPA, 150microg rPA+150microg of a conjugated 10-mer peptide representing the Bacillus anthracis capsule (conj), or 150microg of conj alone. All dry powder formulations contained MPL and chitosan (ChiSys). Significant anti-rPA titers and anthrax lethal toxin neutralizing antibody (TNA) levels were seen with both rPA containing vaccines, although rPA-specific IgG and TNA levels were reduced in rabbits immunized with rPA plus conj. Nine weeks after immunization, rabbits were exposed to a mean aerosol challenge dose of 278 LD50 of Ames spores. Groups immunized with rPA or with rPA+conj had significant increases in survivor proportions compared to the negative control group by Logrank test (p=0.0001 and 0.003, respectively), and survival was not statistically different for the rPA and rPA+conj immunized groups (p=0.63). These data demonstrate that a single immunization with our dry powder anthrax vaccine can protect against a lethal aerosol spore challenge 9 weeks later.

Using Telemetry Data to Refine Endpoints for New Zealand White Rabbits Challenged with Bacillus anthracis.

PubMed

Dawson, David G; Bower, Kristin A; Burnette, Candace N; Holt, Rebecca K; Swearengen, James R; Dabisch, Paul A; Scorpio, Angelo

2017-11-01

We used a continuous-monitoring digital telemetry system to investigate temperature response in New Zealand White rabbits after inhalation or subcutaneous challenge with Bacillus anthracis. Two spore preparations of B. anthracis Ames A2084 were evaluated by using a nose-only inhalation model, and 2 strains, B. anthracis Ames A2084 and B. anthracis UT500, were evaluated in a subcutaneous model. Animal body temperature greater than 3 SD above the mean baseline temperature was considered a significant increase in body temperature (SIBT). All rabbits that exhibited SIBT after challenge by either route of infection or bacterial strain eventually died or were euthanized due to infection, and all rabbits that died or were euthanized due to infection exhibited SIBT during the course of disease. The time at onset of SIBT preceded clinical signs of disease in 94% of the rabbits tested by as long as 2 days. In addition, continuous temperature monitoring facilitated discrimination between the 2 B. anthracis strains with regard to the time interval between SIBT and death. These data suggest that for the New Zealand White rabbit anthrax model, SIBT is a reliable indicator of infection, is predictive of experimental outcome in the absence of treatment, and is measurable prior to the appearance of more severe signs of disease. The use of digital telemetry to monitor infectious disease course in animal models of anthrax can potentially be used in conjunction with other clinical score metrics to refine endpoint euthanasia criteria.

Thermal Analyses of a Human Kidney and a Rabbit Kidney During Cryopreservation by Vitrification.

PubMed

Ehrlich, Lili E; Fahy, Gregory M; Wowk, Brian G; Malen, Jonathan A; Rabin, Yoed

2018-01-01

This study focuses on thermal analysis of the problem of scaling up from the vitrification of rabbit kidneys to the vitrification of human kidneys, where vitrification is the preservation of biological material in the glassy state. The basis for this study is a successful cryopreservation protocol for a rabbit kidney model, based on using a proprietary vitrification solution known as M22. Using the finite element analysis (FEA) commercial code ANSYS, heat transfer simulations suggest that indeed the rabbit kidney unquestionably cools rapidly enough to be vitrified based on known intrarenal concentrations of M22. Scaling up 21-fold, computer simulations suggest less favorable conditions for human kidney vitrification. In this case, cooling rates below -100 °C are sometimes slower than 1 °C/min, a rate that provides a clear-cut margin of safety at all temperatures based on the stability of rabbit kidneys in past studies. Nevertheless, it is concluded in this study that vitrifying human kidneys is possible without significant ice damage, assuming that human kidneys can be perfused with M22 as effectively as rabbit kidneys. The thermal analysis suggests that cooling rates can be further increased by a careful design of the cryogenic protocol and by tailoring the container to the shape of the kidney, in contrast to the present cylindrical container. This study demonstrates the critical need for the thermal analysis of experimental cryopreservation and highlights the unmet need for measuring the thermophysical properties of cryoprotective solutions under conditions relevant to realistic thermal histories.

Defibrotide reduces infarct size in a rabbit model of experimental myocardial ischaemia and reperfusion.

PubMed Central

Thiemermann, C.; Thomas, G. R.; Vane, J. R.

1989-01-01

1. Defibrotide, a single-stranded polydeoxyribonucleotide obtained from bovine lungs, has significant anti-thrombotic, pro-fibrinolytic and prostacyclin-stimulating properties. 2. The present study was designed to evaluate the effects of defibrotide on infarct size and regional myocardial blood flow in a rabbit model of myocardial ischaemia and reperfusion. 3. Defibrotide (32 mg kg-1 bolus + 32 mg kg-1 h-1, i.v.) either with or without co-administration of indomethacin (5 mg kg-1 x 2, i.v.) was administered 5 min after occlusion of the left anterior-lateral coronary artery and continued during the 60 min occlusion and subsequent 3 h reperfusion periods. 4. Defibrotide significantly attenuated the ischaemia-induced ST-segment elevation and abolished the reperfusion-related changes (R-wave reduction and Q-wave development) in the electrocardiogram. In addition, defibrotide significantly improved myocardial blood flow in normal and in ischaemic, but not in infarcted sections of the heart. The improvement in blood flow in normal perfused myocardium, but not in the ischaemic area was prevented by indomethacin. 5. Although the area at risk was similar in all animal groups studied, defibrotide treatment resulted in a 51% reduction of infarct size. Indomethacin treatment abolished the reduction of infarct size seen with defibrotide alone. 6. The data demonstrate a considerable cardioprotective effect of defibrotide in the reperfused ischaemic rabbit myocardium. This effect may be related, at least in part, to a stimulation of endogenous prostaglandin formation. Other possible mechanisms are discussed. PMID:2758223

[The therapeutic effect of nanometer silver impregnated dressing on gunshot wounds after being immersed in brine and tapwater in rabbits].

PubMed

Chen, Bi; Ding, Guo-bin; Tang, Chao-wu

2004-03-22

To investigate the therapeutic effect of nanometer silver impregnated dressing on gunshot wounds after being immersed in brine and tapwater in rabbits. Rabbits were randomly divided into two groups after receiving gunshot wounds in both lower limbs. In group 1, the wounded limbs on the experimental side were immersed in brine for 5 h; in group 2, the wounded limbs on experimental side were immersed in tapwater for 5 h. All the wounds were treated with nanometer silver impregnated dressing on the experimental sides, while those of the control sides were treated with vaseline dressing. Biopsy was done after 30 min and 1, 2, 3, 4, 5 h, respectively. In group 1, the onset of inflammation around the wounds of the experimental sides was delayed, the inflammatory response was less serious, and the wounds were dry with less exudation compared to the controls. The mean healing time of the entry wounds on experimental and control sides was (29.4 +/- 6.6) d and (36.3 +/- 6.0) d (P < 0.01), respectively, and that of the exit wounds on experimental and control sides was (20.1 +/- 6.0) d and (27.3 +/- 5.7) d (P < 0.01), respectively. In group 2, only one of the experimental wounds showed mild inflammation, while all of the control wounds showed serious inflammation with much exudation. The mean healing time of the entry wounds on experimentsides was (13.0 +/- 1.52) d, while that on control sides was (16.0 +/- 3.10) d (P < 0.01). The mean healing time of exit wounds on experimental sides was (11.0 +/- 2.75) d, and those of the control sides was (15.6 +/- 2.85) d (P < 0.01). The nanometer silver impregnated dressing can control infection and accelerate healing in gunshot wounds in rabbits.

Alternation of histone and DNA methylation in human atherosclerotic carotid plaques.

PubMed

Greißel, A; Culmes, M; Napieralski, R; Wagner, E; Gebhard, H; Schmitt, M; Zimmermann, A; Eckstein, H-H; Zernecke, A; Pelisek, J

2015-08-01

Little is known about epigenetics and its possible role in atherosclerosis. We here analysed histone and DNA methylation and the expression of corresponding methyltransferases in early and advanced human atherosclerotic carotid lesions in comparison to healthy carotid arteries. Western Blotting was performed on carotid plaques from our biobank with early (n=60) or advanced (n=60) stages of atherosclerosis and healthy carotid arteries (n=12) to analyse di-methylation patterns of histone H3 at positions K4, K9 and K27. In atherosclerotic lesions, di-methylation of H3K4 was unaltered and that of H3K9 and H3K27 significantly decreased compared to control arteries. Immunohistochemistry revealed an increased appearance of di-methylated H3K4 in smooth muscle cells (SMCs), a decreased expression of di-methylated H3K9 in SMCs and inflammatory cells, and reduced di-methylated H3K27 in inflammatory cells in advanced versus early atherosclerosis. Expression of corresponding histone methyltransferases MLL2 and G9a was increased in advanced versus early atherosclerosis. Genomic DNA hypomethylation, as determined by PCR for methylated LINE1 and SAT-alpha, was observed in early and advanced plaques compared to control arteries and in cell-free serum of patients with high-grade carotid stenosis compared to healthy volunteers. In contrast, no differences in DNA methylation were observed in blood cells. Expression of DNA-methyltransferase DNMT1 was reduced in atherosclerotic plaques versus controls, DNMT3A was undetectable, and DNMT3B not altered. DNA-demethylase TET1 was increased in atherosclerosisc plaques. The extent of histone and DNA methylation and expression of some corresponding methyltransferases are significantly altered in atherosclerosis, suggesting a possible contribution of epigenetics in disease development.

Arsenic exacerbates atherosclerotic lesion formation and inflammation in ApoE-/- mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Srivastava, Sanjay, E-mail: sanjay@louisville.ed; Center for Environmental Genomics and Integrative Biology, University of Louisville, Louisville, KY 40202; Vladykovskaya, Elena N.

2009-11-15

Exposure to arsenic-contaminated water has been shown to be associated with cardiovascular disease, especially atherosclerosis. We examined the effect of arsenic exposure on atherosclerotic lesion formation, lesion composition and nature in ApoE-/- mice. Early post-natal exposure (3-week-old mice exposed to 49 ppm arsenic as NaAsO{sub 2} in drinking water for 7 weeks) increased the atherosclerotic lesion formation by 3- to 5-fold in the aortic valve and the aortic arch, without affecting plasma cholesterol. Exposure to arsenic for 13 weeks (3-week-old mice exposed to 1, 4.9 and 49 ppm arsenic as NaAsO{sub 2} in drinking water) increased the lesion formation andmore » macrophage accumulation in a dose-dependent manner. Temporal studies showed that continuous arsenic exposure significantly exacerbated the lesion formation throughout the aortic tree at 16 and 36 weeks of age. Withdrawal of arsenic for 12 weeks after an initial exposure for 21 weeks (to 3-week-old mice) significantly decreased lesion formation as compared with mice continuously exposed to arsenic. Similarly, adult exposure to 49 ppm arsenic for 24 weeks, starting at 12 weeks of age increased lesion formation by 2- to 3.6-fold in the aortic valve, the aortic arch and the abdominal aorta. Lesions of arsenic-exposed mice displayed a 1.8-fold increase in macrophage accumulation whereas smooth muscle cell and T-lymphocyte contents were not changed. Expression of pro-inflammatory chemokine MCP-1 and cytokine IL-6 and markers of oxidative stress, protein-HNE and protein-MDA adducts were markedly increased in lesions of arsenic-exposed mice. Plasma concentrations of MCP-1, IL-6 and MDA were also significantly elevated in arsenic-exposed mice. These data suggest that arsenic exposure increases oxidative stress, inflammation and atherosclerotic lesion formation.« less

Nephrotoxicity in rabbits after long-term nandrolone decanoate administration.

PubMed

Tsitsimpikou, Christina; Vasilaki, Fotini; Tsarouhas, Konstantinos; Fragkiadaki, Persefoni; Tzardi, Maria; Goutzourelas, Nikolaos; Nepka, Charitini; Kalogeraki, Alexandra; Heretis, Ioannis; Epitropaki, Zoi; Kouretas, Dimitrios; Tsatsakis, Aristidis M

2016-09-30

Among the various side effects of supra-physiological dose of anabolic androgenic steroids that are described, renal toxicity remains the least evaluated. The present study provides evidence that long-term administration of nandrolone decanoate could lead to alterations of renal function and structure in the experimental rabbit model. A pronounced increase in serum urea, creatinine, SGOT and SGPT is observed in the treated animals, with intramuscular administration being more detrimental. Histopathological evaluation of kidneys indicated hyperaemia, fibrosis and focal inflammation. Furthermore, the significantly increased telomerase activity found in the kidneys of the intramuscularly treated animals could possibly represent a counteracting survival mechanism. Oxidative stress markers that were influenced the most were TBARS, indicating lipid peroxidation, and GSH. An interesting finding in our study though, was that while intramuscular administration showed the highest biochemical derangement, oxidative stress markers provided mixed results between intramuscularly and subcutaneously treated rabbits. In conclusion, nephrotoxicity of nandrolone decanoate remains a multi-factorial, partly irreversible effect that involves augmented tissue oxidative status. Copyright © 2016. Published by Elsevier Ireland Ltd.

SRXRF Study of Chemical Elements Content in the Atherosclerotic Plaque of Heart Vessels

NASA Astrophysics Data System (ADS)

Zhuravskaya, E. Ya.; Savchenko, T. I.; Chankina, O. V.; Polonskaya, Ya. V.; Chernyavskii, A. M.; Ragino, Yu. I.; Shcherbakova, L. V.

The SRXRF method has made it possible, for the first time, to determine the multielement composition in the atherosclerotic substrates of heart vessels after surgical interventions. The main advantage of the method is the possibility to analyze small samples without their destruction. As the amount of material to test is insufficient, we have developed a special technique for sample preparation. The concentrations of K, Ca, Cr, Mn, Fe, Co, Ni, Cu, Zn, Br, Sr, Zr, and Pb were measured in stable and unstable plaques. In all the samples studied, Ca is dominating, particularly, in the unstable plaque. No reliable difference was established for other elements measured. A high degree of the association of Ca with Fe, Zn and Sr has been revealed in the atherosclerotic plaques. Measurements were performed using SR from the VEPP-3 storage ring.

Chlamydia pneumoniae Infection in Atherosclerotic Lesion Development through Oxidative Stress: A Brief Overview

PubMed Central

Di Pietro, Marisa; Filardo, Simone; De Santis, Fiorenzo; Sessa, Rosa

2013-01-01

Chlamydia pneumoniae, an obligate intracellular pathogen, is known as a leading cause of respiratory tract infections and, in the last two decades, has been widely associated with atherosclerosis by seroepidemiological studies, and direct detection of the microorganism within atheroma. C. pneumoniae is presumed to play a role in atherosclerosis for its ability to disseminate via peripheral blood mononuclear cells, to replicate and persist within vascular cells, and for its pro-inflammatory and angiogenic effects. Once inside the vascular tissue, C. pneumoniae infection has been shown to induce the production of reactive oxygen species in all the cells involved in atherosclerotic process such as macrophages, platelets, endothelial cells, and vascular smooth muscle cells, leading to oxidative stress. The aim of this review is to summarize the data linking C. pneumoniae-induced oxidative stress to atherosclerotic lesion development. PMID:23877837

Renal Artery Stenting in Patients With Documented Resistant Hypertension and Atherosclerotic Renal Artery Stenosis (ANDORRA)

ClinicalTrials.gov

2018-01-24

Hypertension; Hypertension Resistant to Conventional Therapy; Angiographically Proven Grade III Unilateral or Bilateral Atherosclerotic Renal Artery Stenosis (ARAS) Greater Than or Equal to 60 Percent

HDL mimetic peptide CER-522 treatment regresses left ventricular diastolic dysfunction in cholesterol-fed rabbits.

PubMed

Merlet, Nolwenn; Busseuil, David; Mihalache-Avram, Teodora; Mecteau, Melanie; Shi, Yanfen; Nachar, Walid; Brand, Genevieve; Brodeur, Mathieu R; Charpentier, Daniel; Rhainds, David; Sy, Gavin; Schwendeman, Anna; Lalwani, Narendra; Dasseux, Jean-Louis; Rhéaume, Eric; Tardif, Jean-Claude

2016-07-15

High-density lipoprotein (HDL) infusions induce rapid improvement of experimental atherosclerosis in rabbits but their effect on ventricular function remains unknown. We aimed to evaluate the effects of the HDL mimetic peptide CER-522 on left ventricular diastolic dysfunction (LVDD). Rabbits were fed with a cholesterol- and vitamin D2-enriched diet until mild aortic valve stenosis and hypercholesterolemia-induced LV hypertrophy and LVDD developed. Animals then received saline or 10 or 30mg/kg CER-522 infusions 6 times over 2weeks. We performed serial echocardiograms and LV histology to evaluate the effects of CER-522 therapy on LVDD. LVDD was reduced by CER-522 as shown by multiple parameters including early filling mitral deceleration time, deceleration rate, Em/Am ratio, E/Em ratio, pulmonary venous velocities, and LVDD score. These findings were associated with reduced macrophages (RAM-11 positive cells) in the pericoronary area and LV, and decreased levels of apoptotic cardiomyocytes in CER-522-treated rabbits. CER-522 treatment also resulted in decreased atheromatous plaques and internal elastic lamina area in coronary arteries. CER-522 improves LVDD in rabbits, with reductions of LV macrophage accumulation, cardiomyocyte apoptosis, coronary atherosclerosis and remodelling. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effect of dietary inclusion of sorghum milling waste on growth response, nutrient utilisation, gut characteristics and cecal microflora of weaner rabbits.

PubMed

Oso, Oladele A; Sobayo, Richard; Jegede, Vincent; Fafiolu, Adeboye; Iyasere, Oluwaseun Serah; Dele, Peter; Bamgbose, Adeyemi; Cecilia, Adesida

2011-06-01

Growth response, nutrient digestibility and cecal microflora of 80 male, mixed breed weaner rabbits fed with varying dietary inclusions of sorghum milling waste (SMW) was investigated. Four experimental diets were formulated such that SMW was included at 0 (control), 100, 200 and 300 g/kg, respectively. Each dietary treatment was performed on 20 rabbits. Feed intake increased (P < 0.05) while final live weight and feed conversion ratio of rabbits decreased (P < 0.05) following increased dietary inclusion of SMW. Rabbits fed with 100 and 200 g/kg SMW had similar feed conversion ratios, weight gain, crude fiber, dry matter and crude protein digestibility values. Rabbits fed with 300 g/kg SMW recorded the lowest (P < 0.05) hot carcass weight, dressing percentage and rack weight. Similar dressing percentage and rack weight were recorded for rabbits fed with control diet, 100 and 200 g/kg SMW. The weight of cecal content increased (P < 0.05) with increased dietary inclusion levels of SMW. Rabbits fed with 300 g/kg SMW recorded the lowest (P < 0.05) coliform and lactobaccillus counts. Dietary inclusion of up to 200 g/kg SMW supported improved growth response and carcass yield without imposing any detrimental effect on cecal microflora. © 2011 The Authors; Animal Science Journal © 2011 Japanese Society of Animal Science.

Calcium transport in the early conceptus and associated maternal tissues in the rabbit

PubMed Central

McIntosh, J. E. A.; Lutwak-Mann, C.

1974-01-01

1. The kinetics of calcium transport were studied in unmated (oestrous) and pregnant rabbits in the first half of gestation, with the aim of establishing evidence of hormonal (ovarian) influence on the pattern of transport. 2. The following tissues were examined at short- (45min and 2h) and long-duration (4, 16 and 48h) intervals after parenteral administration of 45Ca or 47Ca: maternal blood plasma, endometrium, uterine fluid, placental tissues, two developmentally disparate stages of rabbit conceptus, namely the unattached blastocyst and the early post-implantation foetus, and bone (femur). 3. Marked variability in calcium content characterized rabbit tissues and body fluids. 4. Compartmental analysis was applied to measurements of specific radioactivity. Oestrous endometrium had the largest rapidly exchanging calcium fraction (turnover time of 12min) and the highest value for calcium flux (500μg of Ca exchanged/h per g fresh wt. of tissue). A marked downward gradient in values of flux existed between the progestational endometrium, uterine fluid and blastocyst; there was a similar gradient between placental tissues and foetus. 5. An hormonal influence on calcium transport was evident in (i) the decrease in specific radioactivity of rabbit blood plasma with advancing pregnancy, (ii) the extraordinarily rapid calcium transport between blood plasma and endometrium, especially in the oestrous stage, and (iii) the effectiveness of ovarian hormone substitution in ovariectomized rabbits. 6. The very low specific radioactivity recorded for bone indicated that only a minute fraction of its calcium was exchanging with that of blood plasma under the experimental conditions examined. 7. The rate of uptake of 45Ca by rabbit blastocysts growing in vitro was one-tenth of that of 22Na, or that recorded for calcium in vivo. 8. Inhibition of carbonic anhydrase activity with acetazolamide in vivo, in maternal erythrocytes, endometrium and placental tissues, produced no

Substantial numerical decline in South Australian rabbit populations following the detection of rabbit haemorrhagic disease virus 2.

PubMed

Mutze, Greg; De Preu, Nicki; Mooney, Trish; Koerner, Dylan; McKenzie, Darren; Sinclair, Ron; Kovaliskli, John; Peacock, David

2018-05-19

Lagovirus europaeus GI.2, also commonly known as rabbit haemorrhagic disease virus 2, was first detected at two long-term monitoring sites for European rabbits, Oryctolagus cuniculus , in South Australia, in mid-2016. Numbers of rabbits in the following 12-18 months were reduced to approximately 20 per cent of average numbers in the preceding 10 years. The impact recorded at the two South Australian sites, if widespread in Australia and persistent for several years, is likely to be of enormous economic and environmental benefit. © British Veterinary Association (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.