Measurement of flow speed in the channels of novel threadlike structures on the surfaces of mammalian organs

NASA Astrophysics Data System (ADS)

Sung, Baeckkyoung; Kim, Min Su; Lee, Byung-Cheon; Yoo, Jung Sun; Lee, Sang-Hee; Kim, Youn-Joong; Kim, Ki-Woo; Soh, Kwang-Sup

2008-02-01

There have been several reports on novel threadlike structures (NTSs) on the surfaces of the internal organs of rats and rabbits since their first observation by Bonghan Kim in 1963. To confirm this novel circulatory function, it is necessary to observe the flow of liquid through the NTS as well as the structurally corroborating channels in the NTS. In this article, we report on the measurement of the flow speed of Alcian blue solution in the NTSs on the organ surfaces of rabbits, and we present electron microscopic images depicting the cribrous cross-section with channels. The speed was measured as 0.3 ± 0.1 mm/s, and the flow distance was up to 12 cm. The flow was unidirectional, and the phase contrast microscopic images showed that the NTSs were strongly stained with Alcian blue. The ultrastructure of the NTSs revealed by cryo-scanning electron microscopy and high-voltage electron microscopy showed that (1) there were cell-like bodies and globular clumps of matter inside the sinus of the channel with thin strands of segregated zones which is a microscopic evidence of the liquid flow, (2) the sinuses have wall structures surrounded with extracellular matrices of collagenous fibers, and (3) there exists a cribriform structure of sinuses. To understand the mechanism for the circulation, a quantitative analysis of the flow speed has been undertaken applying a simplified windkessel model. In this analysis, it was shown that the liquid flow through the NTSs could be due to peristaltic motion of the NTS itself.

Influence of a collagen membrane positioned subjacent the sinus mucosa following the elevation of the maxillary sinus. A histomorphometric study in rabbits.

PubMed

Iida, Takahisa; Carneiro Martins Neto, Evandro; Botticelli, Daniele; Apaza Alccayhuaman, Karol Alí; Lang, Niklaus P; Xavier, Samuel P

2017-12-01

To evaluate the healing after elevation of the sinus mucosa when a collagen membrane was placed between the sinus mucosa and a xenograft used as filler. Eighteen rabbits were used. Sinus mucosa elevation was performed bilaterally, and a collagen membrane was applied subjacent to the sinus mucosa only at a randomly selected test site. At both sites, a collagenated corticocancellous porcine bone was placed within the elevated space and the access window was covered with a collagen membrane. The animals were sacrificed after 2, 4, and 8 weeks of healing, six animals for group. Ground sections were prepared. At the histomorphometric evaluation, the elevated area after 2 and 8 weeks was 11.8 and 8.8 mm 2 at the test, and 10.0 and 5.3 mm 2 at the control sites, respectively. The available area was obtained subtracting the remaining area occupied by the membrane from the elevated area and, after 8 weeks, was 6.7 ± 0.9 mm 2 . After 8 weeks of healing, the mineralized new bone within the elevated space was 18.2 ± 5.5% at the test and 26.7 ± 7.7% at the control sites. Within the available space at the test site, the percentage was 27.3 ± 7.0% after 8 weeks of healing. At 2 and 8 weeks of healing, within the elevated space, the xenograft proportion was 30.9 ± 4.4% and 6.9 ± 2.8% at the test, and 35.2 ± 7.3% and 9.6 ± 4.9% at the control sites, respectively. The placement of a collagen membrane subjacent the sinus mucosa did not reveal any major morphometric difference. The collagen membrane was not completely resorbed after 8 weeks. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effects of atorvastatin on atrial remodeling in a rabbit model of atrial fibrillation produced by rapid atrial pacing.

PubMed

Yang, Qian; Qi, Xiaoyong; Dang, Yi; Li, Yingxiao; Song, Xuelian; Hao, Xiao

2016-06-24

Accumulating evidence suggests that myeloperoxidase (MPO) is involved in atrial remodeling of atrial fibrillation (AF). Statins could reduce the MPO levels in patients with cardiovascular diseases. This study evaluated the effects of atorvastatin on MPO level and atrial remodeling in a rabbit model of pacing-induced AF. Eighteen rabbits were randomly divided into sham, control and atorvastatin groups. Rabbits in the control and atorvastatin groups were subjected to rapid atrial pacing (RAP) at 600 bpm for 3 weeks, and treated with placebo or atorvastatin (2.5 mg/kg/d), respectively. Rabbits in the sham group did not receive RAP. After 3 weeks of pacing, atrial structural and functional changes were assessed by echocardiography, atrial effective refractory period (AERP) and AF inducibility were measured by atrial electrophysiological examination, and histological changes were evaluated by Masson trichrome-staining. The L-type calcium channel α1c (Cav1.2), collagen I and III, MPO, matrix metalloproteinase (MMP)-2 and MMP-9 were analyzed by real time polymerase chain reaction and/or western blot. All rabbits were found to have maintained sinus rhythm after 3 weeks of RAP. Atrial burst stimulation induced sustained AF (>30 min) in 5, 4, and no rabbits in the control, atorvastatin, and sham groups, respectively. The AERP shortened and Cav1.2 mRNA level decreased in the control group, but these changes were suppressed in the atorvastatin group. Obvious left atrial enlargement and dysfunction was found in both control and atorvastatin groups. Compared with the control group, these echocardiograhic indices of left atrium did not differ in the atorvastatin group. Prominent atrial fibrosis and increased levels of collagen I and III were observed in the control group but not in the atorvastatin group. The mRNA and protein levels of MPO, MMP-2 and MMP-9 significantly increased in the control group, but these changes were prevented in the atorvastatin group. Treatment with atorvastatin prevented atrial remodeling in a rabbit model of RAP-induced AF. The reduction of levels of atrial MPO, MMP-2 and MMP-9 may contribute to the prevention of atorvastatin on atrial remodeling.

In vitro and in vivo evaluation of strontium-containing nanostructured carbonated hydroxyapatite/sodium alginate for sinus lift in rabbits.

PubMed

Valiense, Helder; Barreto, Mauricio; Resende, Rodrigo F; Alves, Adriana T; Rossi, Alexandre M; Mavropoulos, Elena; Granjeiro, José M; Calasans-Maia, Mônica D

2016-02-01

Various synthetic bone substitutes have been developed to reconstruct bone defects. One of the most prevalent ceramics in bone treatment is hydroxyapatite (HA) that is a useful material as bone substitute, however, with a low rate of biodegradation. Its structure allows isomorphic cationic and anionic substitutions to be easily introduced, which can alter the crystallinity, morphology, biocompatibility, and osteoconductivity. The objective of this study was to investigate the in vitro and in vivo biological responses to strontium-containing nanostructured carbonated HA/sodium alginate (SrCHA) spheres (425<ϕ <600 μm) that were used for sinus lifts in rabbits using nanostructured carbonated HA/sodium alginate (CHA) as a reference. Cytocompatibility was determined using a multiparametric assay after exposing murine preosteoblasts to the extracts of these materials. Twelve male and female rabbits underwent bilateral sinus lift procedures and were divided into two groups (CHA or SrCHA) and in two experimental periods (4 and 12 weeks), for microscopic and histomorphometric analyses. The in vitro test revealed the overall viability of the cells exposed to the CHA and SrCHA extracts; thus, these extracts were considered cytocompatible, which was confirmed by three different parameters in the in vitro tests. The histological analysis showed chronic inflammation with a prevalence of macrophages around the CHA spheres after 4 weeks, and this inflammation decreased after 12 weeks. Bone formation was observed in both groups, and smaller quantities of SrCHA spheres were observed after 12 weeks, indicating greater bioresorption of SrCHA than CHA. SrCHA spheres are biocompatible and osteoconductive and undergo bioresorption earlier than CHA spheres. © 2015 Wiley Periodicals, Inc.

Experimental Evaluation of the Effectiveness of Demineralized Bone Matrix and Collagenated Heterologous Bone Grafts Used Alone or in Combination with Platelet-Rich Fibrin on Bone Healing in Sinus Floor Augmentation.

PubMed

Peker, Elif; Karaca, Inci Rana; Yildirim, Benay

2016-01-01

The aim of this study was an experimental evaluation of the effectiveness of demineralized bone matrix (DBM) and collagenated heterologous bone graft (CHBG) used alone or in combination with platelet-rich fibrin on bone healing in sinus floor augmentation procedures. In this study, 36 New Zealand rabbits were used. The bilateral sinus elevation was performed, and 72 defects were obtained. The rabbit maxillary sinuses were divided into four groups according to the augmentation biomaterials obtained: demineralized bone matrix (Grafton DBM Putty, Osteotech; DBM group), DBM combined with platelet-rich fibrin (PRF; DBM + PRF group), collagenated heterologous bone graft (CHBG; Apatos Mix, OsteoBiol, Tecnoss; CHBG group), CHBG combined with PRF (CHBG + PRF group). All groups were sacrificed at 2, 4, and 8 weeks after surgery for histologic, histomorphometric, and immunohistochemical analyses. The inflammatory reaction was moderate to intense at the second week in all groups and declined from 2 to 8 weeks. New bone formation was started at the second week and increased from 2 to 8 weeks in all groups. There was no significant difference in bone formation between the experimental groups that used PRF mixed graft material and control groups that used only graft material. The percentage of new bone formation showed a significant difference in DBM groups and DBM + PRF groups compared with other groups. There were osteoclasts around all the bone graft materials used, but the percentage of residual graft particles was significantly higher in CHBG groups and CHBG + PRF groups at the eighth week. There is no beneficial effect of the application of PRF in combination with demineralized bone matrix or collagenated heterologous bone graft on bone formation in sinus floor augmentation. The results of this study showed that both collagenated heterologous bone graft and demineralized bone matrix have osteoconductive properties, but demineralized bone matrix showed more bone formation than collagenated heterologous bone graft.

Diadenosine Polyphosphates Suppress the Effects of Sympathetic Nerve Stimulation in Rabbit Heart Pacemaker.

PubMed

Abramochkin, D V; Pustovit, K B; Kuz'min, V S

2017-09-01

The modulatory influence of diadenosine tetraphosphate (Ap4A) and diadenosine pentaphosphate (Ap5A) on the effect of intramural autonomic nerve stimulation in isolated rabbit sinoatrial node were examined. Electrical activity of the sinoatrial node was recorded intracellularly. Against the background of blockade of adrenergic effects with propranolol (3×10 -6 M) or in preparations isolated 2 h after injection of reserpine (2 mg/kg), nerve stimulation induced short-term membrane hyperpolarization and diminished the sinus node firing rate. These phenomena were not affected by Ap4A or Ap5A (10 -5 M). Under the action of atropine (3×10 -6 M) that completely eliminated the cholinergic influences, nerve stimulation enhanced the sinus node firing rate by 17.30±3.45% from the initial rate. Both Ap4A and Ap5A moderated the stimulation-induced elevation of firing rate to 9.9±2.8 and 10.5±2.9%, respectively. The data suggest that diadenosine polyphosphates significantly modulate the sympathetic influences on the heart rhythm, but have no effect on the parasympathetic control over activity of sinoatrial node.

The effects of the stem cell on ciliary regeneration of injured rabbit sinonasal epithelium.

PubMed

Kavuzlu, Ali; Tatar, Emel Çadallı; Karagöz, Tuğba; Pınarlı, Ferda Alpaslan; Tatar, İlkan; Bayır, Ömer; Korkmaz, Mehmet Hakan

2017-08-01

Defects in mucosal healing after sinonasal surgery cause infection, scar formation causing obstruction, relapse of the disease within a shorter period and revision surgery. The present study aimed to create a functional ciliated epithelium using a stem cell and stem cell sheet of adipose tissue origin and to show such regeneration ultra-structurally on experimentally injured rabbit nasal epithelium. This was an experimental animal study and basic research. A total of 18 white New Zealand rabbits were divided into three groups. The medial wall of the maxillary sinus of the subjects was peeled off bilaterally. No additional procedure was applied to the subjects in Group 1. In Group 2, adipose tissue-derived mesenchymal stem cell was implanted on the wound edges of the subjects. In Group 3, a stem cell sheet of three layers was laid onto the defect area. All subjects were killed after 3 weeks. The presence of the stem cell stained with bromo-deoxyuridine was assessed with a light microscope, whereas cilia density, ciliated orientation and cilia structure were evaluated with a scanning electron microscope. Ciliary densities in Group 2 and Group 3 were statistically superior compared to the control group (p < 0.001, p = 0.007). Cilia morphology in Group 2 and Group 3 was also better than the control group (p < 0.01, p = 0.048). Ciliary orientation in Group 2 was scored highest (p < 0.01). The ratio of BrDu-stained cells was observed to be 27% in Group 3 and 8% in Group 2. Sub-epithelial recovery was observed to be better in Group 3. Adipose tissue-derived mesenchymal stem cell increased the healing of the injured maxillary sinus mucosa of the rabbits in terms of cilia presence, density and morphology regardless of the implementation technique. Level of evidence NA.

The use of injectable sonication-induced silk hydrogel for VEGF165 and BMP-2 delivery for elevation of the maxillary sinus floor

PubMed Central

Zhang, Wenjie; Wang, Xiuli; Wang, Shaoyi; Zhao, Jun; Xu, Lianyi; Zhu, Chao; Zeng, Deliang; Chen, Jake; Zhang, Zhiyuan; Kaplan, David L.; Jiang, Xinquan

2011-01-01

Sonication-induced silk hydrogels were previously prepared as an injectable bone replacement biomaterial, with a need to improve osteogenic features. Vascular endothelial growth factor (VEGF165) and bone morphogenic protein-2 (BMP-2) are key regulators of angiogenesis and osteogenesis, respectively, during bone regeneration. Therefore, the present study aimed at evaluating in situ forming silk hydrogels as a vehicle to encapsulate dual factors for rabbit maxillary sinus floor augmentation. Sonication-induced silk hydrogels were prepared in vitro and the slow release of VEGF165 and BMP-2 from these silk gels was evaluated by ELISA. For in vivo studies for each time point (4 and 12 weeks), 24 sinus floors elevation surgeries were made bilaterally in 12 rabbits for the following four treatment groups: silk gel (group Silk gel), silk gel/VEGF165 (group VEGF), silk gel/BMP-2 (group BMP-2), silk gel/VEGF165/BMP-2 (group V+B) (n=6 per group). Sequential florescent labeling and radiographic observations were used to record new bone formation and mineralization, along with histological and histomorphometric analysis. At week 4, VEGF165 promoted more tissue infiltration into the gel and accelerated the degradation of the gel material. At this time point, the bone area in group V+B was significantly larger than those in the other three groups. At week 12, elevated sinus floor heights of groups BMP-2 and V+B were larger than those of the Silk gel and VEGF groups, and the V+B group had the largest new bone area among all groups. In addition, a larger blood vessel area formed in the remaining gel areas in groups VEGF and V+B. In conclusion, VEGF165 and BMP-2 released from injectable and biodegradable silk gels promoted angiogenesis and new bone formation, with the two factors demonstrating an additive effect on bone regeneration. These results indicate that silk hydrogels can be used as an injectable vehicle to deliver multiple growth factors in a minimally invasive approach to regenerate irregular bony cavities. PMID:21889205

[Design of cross-sectional anatomical model focused on drainage pathways of paranasal sinuses].

PubMed

Zha, Y; Lv, W; Gao, Y L; Zhu, Z Z; Gao, Z Q

2018-05-01

Objective: To design and produce cross-sectional anatomical models of paranasal sinuses for the purpose of demonstrating drainage pathways of each nasal sinus for the young doctors. Method: We reconstructed the three-dimensional model of sinuses area based on CT scan data, and divided it into 5 thick cross-sectional anatomy models by 4 coronal plane，which cross middle points of agger nasi cell, ethmoid bulla, posterior ethmoid sinuses and sphenoid sinus respectively. Then a 3D printerwas used to make anatomical cross-sectional anatomical models. Result: Successfully produced a digital 3D printing cross-sectional models of paranasal sinuses. Sinus drainage pathways were observed on the models. Conclusion: The cross-sectional anatomical models made by us can exactly and intuitively demonstrate the ostia of each sinus cell and they can help the young doctors to understand and master the key anatomies and relationships which are important to the endoscopic sinus surgery. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.

Sinusoidal constriction and vascular hypertrophy in the diabetes-induced rabbit penis.

PubMed

Pereira, Vivian Alves; Abidu-Figueiredo, Marcelo; Pereira-Sampaio, Marco Aurelio; Chagas, Mauricio Alves; Costa, Waldemar Silva; Sampaio, Francisco J B

2013-01-01

To assess the morphological changes of penile vascular structures and the corpus cavernosum area in alloxan-induced diabetic rabbits. Twenty male rabbits (2 months old) were divided into two groups with 10 rabbits each, the control group (CG) and the diabetic group (DG). The animals from DG received an intravenous injection of alloxan (100mg/kg) to induce the diabetes. Ten weeks after the induction of diabetes, all animals were euthanized. Two fragments of the penile shaft were harvested and samples were processed and paraffin embedded. Sections (5 µm) were cut and stained for histological and immunohistochemical markers. Nuclear protrusion toward the lumen, and cytoplasmic vacuolization were observed in the tunica intima of the dorsal artery of the penis in DG. The thicknesses of the tunica media increased significantly in DG (p = 0.0350). It was also observed a significant increase in the area of the tunica media (p = 0.0179). There was no significant change in smooth muscle cell density in the tunica media of the dorsal artery of the penis (p = 0.0855). The collagen fiber pattern of the tunica adventitia of the dorsal artery of the penis was different between the control and diabetic groups. There was a significant decrease in the area occupied by the cavernous sinuses in DG (p = 0.0013). Alloxan-induced diabetes mellitus in rabbits promotes important changes in penile vascular structures, thereby decreasing blood supply and affecting penile hemodynamics, leading to erectile dysfunction.

Three-Dimensional Computer Model of the Right Atrium Including the Sinoatrial and Atrioventricular Nodes Predicts Classical Nodal Behaviours

PubMed Central

Li, Jue; Inada, Shin; Schneider, Jurgen E.; Zhang, Henggui; Dobrzynski, Halina; Boyett, Mark R.

2014-01-01

The aim of the study was to develop a three-dimensional (3D) anatomically-detailed model of the rabbit right atrium containing the sinoatrial and atrioventricular nodes to study the electrophysiology of the nodes. A model was generated based on 3D images of a rabbit heart (atria and part of ventricles), obtained using high-resolution magnetic resonance imaging. Segmentation was carried out semi-manually. A 3D right atrium array model (∼3.16 million elements), including eighteen objects, was constructed. For description of cellular electrophysiology, the Rogers-modified FitzHugh-Nagumo model was further modified to allow control of the major characteristics of the action potential with relatively low computational resource requirements. Model parameters were chosen to simulate the action potentials in the sinoatrial node, atrial muscle, inferior nodal extension and penetrating bundle. The block zone was simulated as passive tissue. The sinoatrial node, crista terminalis, main branch and roof bundle were considered as anisotropic. We have simulated normal and abnormal electrophysiology of the two nodes. In accordance with experimental findings: (i) during sinus rhythm, conduction occurs down the interatrial septum and into the atrioventricular node via the fast pathway (conduction down the crista terminalis and into the atrioventricular node via the slow pathway is slower); (ii) during atrial fibrillation, the sinoatrial node is protected from overdrive by its long refractory period; and (iii) during atrial fibrillation, the atrioventricular node reduces the frequency of action potentials reaching the ventricles. The model is able to simulate ventricular echo beats. In summary, a 3D anatomical model of the right atrium containing the cardiac conduction system is able to simulate a wide range of classical nodal behaviours. PMID:25380074

Two- and Three-Dimensional Anatomy of Paranasal Sinuses in Arabian Foals

PubMed Central

BAHAR, Sadullah; BOLAT, Durmus; DAYAN, Mustafa Orhun; PAKSOY, Yahya

2013-01-01

ABSTRACT The 2- and 3-dimensional (3D) anatomy and the morphometric properties of the paranasal sinuses of the foal have received little or no attention in the literature. The aim of this study was to obtain details of the paranasal sinuses using multiplane CT imaging to create 3D models and to determine morphological and morphometric data for the sinuses using the 3D models. The heads of five female foals were used in this study. The heads were scanned using computed tomography (CT) in the rostrocaudal direction. After the heads had been frozen, anatomical sections were obtained in the scan position. The 3D models of sinuses and the skull were prepared using MIMICS®. These models were used to assess the surface area and volume of the sinuses, the width, height and orientation of the apertures connecting these sinuses and finally the planar relation of the sinuses with the skull. The right and left sides of all anatomical structures, except the sphenoid sinuses, had symmetric organization on CT images and anatomical sections. The total sinus surface area and volume on both sides were 214.4 cm2 and 72.9 ml, respectively. The largest and the smallest sinuses were the frontal sinus (41.5 ml) and the middle conchal sinus (0.2 ml), respectively. It was found that the planes bounding the sinuses passed through easily palpable points on the head. In conclusion, 3D modeling in combination with conventional sectional imaging of the paranasal sinuses of the foal may help anatomists, radiologists, clinicians and veterinary students. PMID:24004969

Two- and three-dimensional anatomy of paranasal sinuses in Arabian foals.

PubMed

Bahar, Sadullah; Bolat, Durmus; Dayan, Mustafa Orhun; Paksoy, Yahya

2014-01-01

The 2- and 3-dimensional (3D) anatomy and the morphometric properties of the paranasal sinuses of the foal have received little or no attention in the literature. The aim of this study was to obtain details of the paranasal sinuses using multiplane CT imaging to create 3D models and to determine morphological and morphometric data for the sinuses using the 3D models. The heads of five female foals were used in this study. The heads were scanned using computed tomography (CT) in the rostrocaudal direction. After the heads had been frozen, anatomical sections were obtained in the scan position. The 3D models of sinuses and the skull were prepared using MIMICS(®). These models were used to assess the surface area and volume of the sinuses, the width, height and orientation of the apertures connecting these sinuses and finally the planar relation of the sinuses with the skull. The right and left sides of all anatomical structures, except the sphenoid sinuses, had symmetric organization on CT images and anatomical sections. The total sinus surface area and volume on both sides were 214.4 cm(2) and 72.9 ml, respectively. The largest and the smallest sinuses were the frontal sinus (41.5 ml) and the middle conchal sinus (0.2 ml), respectively. It was found that the planes bounding the sinuses passed through easily palpable points on the head. In conclusion, 3D modeling in combination with conventional sectional imaging of the paranasal sinuses of the foal may help anatomists, radiologists, clinicians and veterinary students.

Maxillary sinus floor elevation using a tissue-engineered bone with calcium-magnesium phosphate cement and bone marrow stromal cells in rabbits.

PubMed

Zeng, Deliang; Xia, Lunguo; Zhang, Wenjie; Huang, Hui; Wei, Bin; Huang, Qingfeng; Wei, Jie; Liu, Changsheng; Jiang, Xinquan

2012-04-01

The objective of this study was to assess the effects of maxillary sinus floor elevation with a tissue-engineered bone constructed with bone marrow stromal cells (bMSCs) and calcium-magnesium phosphate cement (CMPC) material. The calcium (Ca), magnesium (Mg), and phosphorus (P) ions released from calcium phosphate cement (CPC), magnesium phosphate cement (MPC), and CMPC were detected by inductively coupled plasma atomic emission spectroscopy (ICP-AES), and the proliferation and osteogenic differentiation of bMSCs seeded on CPC, MPC, and CMPC or cultured in CPC, MPC, and CMPC extracts were measured by MTT analysis, alkaline phosphatase (ALP) activity assay, alizarin red mineralization assay, and real-time PCR analysis of the osteogenic genes ALP and osteocalcin (OCN). Finally, bMSCs were combined with CPC, MPC, and CMPC and used for maxillary sinus floor elevation in rabbits, while CPC, MPC, or CMPC without cells served as control groups. The new bone formation in each group was detected by histological finding and fluorochrome labeling at weeks 2 and 8 after surgical operation. It was observed that the Ca ion concentrations of the CMPC and CPC scaffolds was significantly higher than that of the MPC scaffold, while the Mg ions concentration of CMPC and MPC was significantly higher than that of CPC. The bMSCs seeded on CMPC and MPC or cultured in their extracts proliferated more quickly than the cells seeded on CPC or cultured in its extract, respectively. The osteogenic differentiation of bMSCs seeded on CMPC and CPC or cultured in the corresponding extracts was significantly enhanced compared to that of bMSCs seeded on MPC or cultured in its extract; however, there was no significant difference between CMPC and CPC. As for maxillary sinus floor elevation in vivo, CMPC could promote more new bone formation and mineralization compared to CPC and MPC, while the addition of bMSCs could further enhance its new bone formation ability significantly. Our data suggest that CMPC possesses moderate biodegradability and excellent osteoconductivity, which may be attributed to its Ca and Mg ion composition, and the tissue-engineered bone constructed of CMPC and bMSCs might be a potential alterative graft for maxillofacial bone regeneration.

Effect of accessory ostia on maxillary sinus ventilation: a computational fluid dynamics (CFD) study.

PubMed

Zhu, Jian Hua; Lee, Heow Pueh; Lim, Kian Meng; Gordon, Bruce R; Wang, De Yun

2012-08-15

We evaluated, by CFD simulation, effects of accessory ostium (AO) on maxillary sinus ventilation. A three-dimensional nasal model was constructed from an adult CT scan with two left maxillary AOs (sinus I) and one right AO (sinus II), then compared to an identical control model with all AOs sealed (sinuses III and IV). Transient simulations of quiet inspiration and expiration at 15 L/min, and nasal blow at 48 L/min, were calculated for both models using low-Reynolds-number turbulent analysis. At low flows, ventilation rates in sinuses with AOs (I ≈ 0.46 L/min, II ≈ 0.54 L/min), were both more than a magnitude higher than sinuses without AOs (II I ≈ 0.019 L/min, IV ≈ 0.020 L/min). Absence of AO almost completely prevented sinus ventilation. Increased ventilation of sinuses with AOs is complex. Under high flow conditions mimicking nose blowing, in sinuses II, III, and IV, the sinus flow rate increased. In contrast, the airflow direction through sinus I reversed between inspiration and expiration, while it remained almost constant throughout the respiration cycle in sinus II. CFD simulation demonstrated that AOs markedly increase maxillary sinus airflow rates and alter sinus air circulation patterns. Whether these airflow changes impact maxillary sinus physiology or pathophysiology is unknown. Copyright © 2012 Elsevier B.V. All rights reserved.

Frontal sinuses and head-butting in goats: a finite element analysis.

PubMed

Farke, Andrew A

2008-10-01

Frontal sinuses in goats and other mammals have been hypothesized to function as shock absorbers, protecting the brain from blows during intraspecific combat. Furthermore, sinuses are thought to form through removal of ;structurally unnecessary' bone. These hypotheses were tested using finite element modeling. Three-dimensional models of domesticated goat (Capra hircus) skulls were constructed, with variable frontal bone and frontal sinus morphology, and loaded to simulate various head-butting behaviors. In general, models with sinuses experienced higher strain energy values (a proxy for shock absorption) than did models with unvaulted frontal bones, and the latter often had higher magnitudes than models with solid vaulted frontal bones. Furthermore, vaulted frontal bones did not reduce magnitudes of principal strain on the surface of the endocranial cavity relative to models with unvaulted frontal bones under most loading conditions. Thus, these results were only partially consistent with sinuses, or the bone that walls the sinuses, acting as shock absorbers. It is hypothesized that the keratinous horn sheaths and cranial sutures are probably more important for absorbing blows to the head. Models with sinuses did exhibit a more ;efficient' distribution of stresses, as visualized by histograms in which models with solid frontal bones had numerous unloaded elements. This is consistent with the hypothesis that sinuses result at least in part from the removal of mechanically unnecessary bone.

Cadaveric validation study of computational fluid dynamics model of sinus irrigations before and after sinus surgery

PubMed Central

Craig, John R; Zhao, Kai; Doan, Ngoc; Khalili, Sammy; Lee, John YK; Adappa, Nithin D; Palmer, James N

2016-01-01

Background Investigations into the distribution of sinus irrigations have been limited by labor-intensive methodologies that do not capture the full dynamics of irrigation flow. The purpose of this study was to validate the accuracy of a computational fluid dynamics (CFD) model for sinonasal irrigations through a cadaveric experiment. Methods Endoscopic sinus surgery was performed on two fresh cadavers to open all eight sinuses, including a Draf III procedure for cadaver 1, and Draf IIb frontal sinusotomies for cadaver 2. Computed tomography maxillofacial scans were obtained preoperatively and postoperatively, from which CFD models were created. Blue-dyed saline in a 240 mL squeeze bottle was used to irrigate cadaver sinuses at 60 mL/s (120 mL per side, over 2 seconds). These parameters were replicated in CFD simulations. Endoscopes were placed through trephinations drilled through the anterior walls of the maxillary and frontal sinuses, and sphenoid roofs. Irrigation flow into the maxillary, frontal, and sphenoid sinuses was graded both ipsilateral and contralateral to the side of nasal irrigation, and then compared with the CFD simulations. Results In both cadavers, preoperative and postoperative irrigation flow into maxillary, frontal, and sphenoid sinuses matched extremely well when comparing the CFD models and cadaver endoscopic videos. For cadaver 1, there was 100% concordance between the CFD model and cadaver videos, and 83% concordance for cadaver 2. Conclusions This cadaveric experiment provided potential validation of the CFD model for simulating saline irrigation flow into the maxillary, frontal, and sphenoid sinuses before and after sinus surgery. PMID:26880742

Substance P antagonists and mucociliary activity in rabbit.

PubMed

Lindberg, S; Mercke, U

1985-06-01

Substance P (SP) is known to accelerate mucociliary (m.c.) activity in the rabbit maxillary sinus in vivo. The physiological significance of this finding was investigated by testing three putative SP antagonists. [Arg5, D-Trp7,9, Nle11]SP5-11 could not be used as an antagonist because it stimulated m.c. activity. [D-Arg1, D-Trp7,9, Leu11]SP had no effect on the m.c. activity changes induced by SP. [D-Pro2, D-Trp7,9]SP was found to be an effective antagonist, 1 mg/kg of this drug reversibly inhibiting both the effects of 0.1 micrograms/kg SP and the stimulating effect of 1.0 micrograms/kg bradykinin and 30.0 micrograms/kg capsaicin; the stimulating effect of 0.5 micrograms/kg methacholine was not inhibited. It is suggested that bradykinin and capsaicin stimulate m.c. activity at least partly by releasing SP. The results of this investigation also support the view that the accelerating effect of SP on m.c. activity reflects physiological SP-mediated protective mechanisms in the airways. It is concluded that [D-Pro2,D-Trp7,9]SP is a useful pharmacological tool for studying the role of SP in the control of m.c. activity in rabbits.

Electrophysiological effects of FK664, a new cardiotonic agent, on preparations from guinea pig ventricle and from rabbit sino-atrial node.

PubMed

Kodama, I; Anno, T; Sudo, Y; Satake, N; Shibata, S

1989-05-01

Effects of the cardiotonic agent FK664, 6-(3, 4-dimethoxy-phenyl)-1-ethyl-4-mesitylimino-3-methyl-3,4-dihydro-2 (1H)-pyrimidone, on isolated guinea pig ventricular muscles and rabbit sinus node pacemaker cells were studied using micro-electrode techniques. In ventricular muscles driven at 0.5-1.0 Hz, FK664 above 3 mumol.litre-1 caused an increase in contractile force and a shortening of time to peak tension. This positive inotropic effect of FK664 was accompanied by a slight elevation of the early plateau phase of the action potential, while other action potential variables were unaffected. The change in contractile force induced by FK664 was abolished in a low Ca2+ medium (0.12 mmol.litre-1) or by treatment with ryanodine (2 mumol.litre-1), whereas it was relatively well preserved in the preparations pretreated with nefedipine (1 mumol.litre-1). The slow action potentials induced by isoprenaline (0.3 mumol.litre-1) in high K+ medium (30 mmol.litre-1) and the slow inward current measured by single sucrose gap voltage clamp at a holding potential of -40 mV were unaffected by FK664. In sinus node pacemaker cells, FK664 (1-10 mumol.litre-1) caused a dose dependent acceleration of phase 4 depolarisation and a shortening of spontaneous firing cycle length. This positive chronotropic effect of FK664 was markedly inhibited in a low Ca2+ medium (0.3 mmol.litre-1). These findings suggest that FK664 has positive inotropic and chronotropic effects on the heart, due to an enhancement of transsarcolemmal calcium influx through the low threshold, dihydropyridine insensitive Ca2+ channel population.

Computational modeling of venous sinus stenosis in idiopathic intracranial hypertension

PubMed Central

Levitt, Michael R; McGah, Patrick M; Moon, Karam; Albuquerque, Felipe C; McDougall, Cameron G; Kalani, M Yashar S; Kim, Louis J; Aliseda, Alberto

2016-01-01

Background and Purpose Idiopathic intracranial hypertension has been associated with dural venous sinus stenosis in some patients, but the hemodynamic environment of the dural venous sinuses has not been quantitatively described. Here, we present the first such computational fluid dynamics model using patient-specific blood pressure measurements. Materials and Methods Six patients with idiopathic intracranial hypertension and at least one stenosis or atresia at the transverse-sigmoid sinus junction underwent MRV followed by cerebral venography and manometry throughout the dural venous sinuses. Patient-specific computational fluid dynamics models were created using MRV anatomy, with venous pressure measurements as boundary conditions. Blood flow and wall shear stress were calculated for each patient. Results Computational models of dural venous sinuses were successfully reconstructed in all six patients with patient-specific boundary conditions. Three patients demonstrated a pathologic pressure gradient (≥ 8 mm Hg) across four dural venous sinus stenoses. Small sample size precludes statistical comparisons, but average overall flow throughout the dural venous sinuses of patients with pathologic pressure gradients was higher than in those without (1041.00 ± 506.52 vs. 358.00 ± 190.95 mL/min). Wall shear stress was also higher across stenoses in patients with pathologic pressure gradients (37.66 ± 48.39 vs 7.02 ± 13.60 Pa). Conclusion The hemodynamic environment of the dural venous sinuses can be computationally modeled using patient-specific anatomy and physiological measurements in patients with idiopathic intracranial hypertension. There was substantially higher blood flow and wall shear stress in patients with pathological pressure gradients. PMID:27197986

Comparing the influence of crestal cortical bone and sinus floor cortical bone in posterior maxilla bi-cortical dental implantation: a three-dimensional finite element analysis.

PubMed

Yan, Xu; Zhang, Xinwen; Chi, Weichao; Ai, Hongjun; Wu, Lin

2015-05-01

This study aimed to compare the influence of alveolar ridge cortical bone and sinus floor cortical bone in sinus areabi-cortical dental implantation by means of 3D finite element analysis. Three-dimensional finite element (FE) models in a posterior maxillary region with sinus membrane and the same height of alveolar ridge of 10 mm were generated according to the anatomical data of the sinus area. They were either with fixed thickness of crestal cortical bone and variable thickness of sinus floor cortical bone or vice versa. Ten models were assumed to be under immediate loading or conventional loading. The standard implant model based on the Nobel Biocare implant system was created via computer-aided design software. All materials were assumed to be isotropic and linearly elastic. An inclined force of 129 N was applied. Von Mises stress mainly concentrated on the surface of crestal cortical bone around the implant neck. For all the models, both the axial and buccolingual resonance frequencies of conventional loading were higher than those of immediate loading; however, the difference is less than 5%. The results showed that bi-cortical implant in sinus area increased the stability of the implant, especially for immediately loading implantation. The thickness of both crestal cortical bone and sinus floor cortical bone influenced implant micromotion and stress distribution; however, crestal cortical bone may be more important than sinus floor cortical bone.

The sinonasal communication in the horse: examinations using computerized three-dimensional reformatted renderings of computed-tomography datasets

PubMed Central

2014-01-01

Background Sinusitis is a common disease in the horse. In human medicine it is described, that obstruction of the sinonasal communication plays a major role in the development of sinusitis. To get spatial sense of the equine specific communication ways between the nasal cavity and the paranasal sinuses, heads of 19 horses, aged 2 to 26 years, were analyzed using three-dimensional (3D) reformatted renderings of CT-datasets. Three-dimensional models were generated following manual and semi-automated segmentation. Before segmentation, the two-dimensional (2D) CT-images were verified against corresponding frozen sections of cadaveric heads. Results Three-dimensional analysis of the paranasal sinuses showed the bilateral existence of seven sinus compartments: rostral maxillary sinus, ventral conchal sinus, caudal maxillary sinus, dorsal conchal sinus, frontal sinus, sphenopalatine sinus and middle conchal sinus. The maxillary septum divides these seven compartments into two sinus systems: a rostral paranasal sinus system composed of the rostral maxillary sinus and the ventral conchal sinus and a caudal paranasal sinus system which comprises all other sinuses. The generated 3D models revealed a typically configuration of the sinonasal communication ways. The sinonasal communication started within the middle nasal meatus at the nasomaxillary aperture (Apertura nasomaxillaris), which opens in a common sinonasal channel (Canalis sinunasalis communis). This common sinonasal channel ramifies into a rostral sinonasal channel (Canalis sinunasalis rostralis) and a caudo-lateral sinonasal channel (Canalis sinunasalis caudalis). The rostral sinonasal channel ventilated the rostral paranasal sinus system, the caudo-lateral sinonasal channel opened into the caudal paranasal sinus system. The rostral sinonasal channel was connected to the rostral paranasal sinuses in various ways. Whereas, the caudal channel showed less anatomical variations and was in all cases connected to the caudal maxillary sinus. Volumetric measurements of the sinonasal channels showed no statistically significant differences (P <0.05) between the right and left side of the head. Conclusions Under physiologic conditions both paranasal sinus systems are connected to the nasal cavity by equine specific sinonasal channels. To resolve sinus disease it is aimed to maintain or even reconstruct the normal anatomy of the sinonasal communication by surgical intervention. Therefore, the presented 3D analyses may provide a useful basis. PMID:24646003

Virtual Reality Model of the Three-Dimensional Anatomy of the Cavernous Sinus Based on a Cadaveric Image and Dissection.

PubMed

Qian, Zeng-Hui; Feng, Xu; Li, Yang; Tang, Ke

2018-01-01

Studying the three-dimensional (3D) anatomy of the cavernous sinus is essential for treating lesions in this region with skull base surgeries. Cadaver dissection is a conventional method that has insurmountable flaws with regard to understanding spatial anatomy. The authors' research aimed to build an image model of the cavernous sinus region in a virtual reality system to precisely, individually and objectively elucidate the complete and local stereo-anatomy. Computed tomography and magnetic resonance imaging scans were performed on 5 adult cadaver heads. Latex mixed with contrast agent was injected into the arterial system and then into the venous system. Computed tomography scans were performed again following the 2 injections. Magnetic resonance imaging scans were performed again after the cranial nerves were exposed. Image data were input into a virtual reality system to establish a model of the cavernous sinus. Observation results of the image models were compared with those of the cadaver heads. Visualization of the cavernous sinus region models built using the virtual reality system was good for all the cadavers. High resolutions were achieved for the images of different tissues. The observed results were consistent with those of the cadaver head. The spatial architecture and modality of the cavernous sinus were clearly displayed in the 3D model by rotating the model and conveniently changing its transparency. A 3D virtual reality model of the cavernous sinus region is helpful for globally and objectively understanding anatomy. The observation procedure was accurate, convenient, noninvasive, and time and specimen saving.

Feasibility of Shape-Memory Ni/Ti Alloy Wire Containing Tube Elevators for Transcrestal Detaching Maxillary Sinus Mucosa: Ex Vivo Study.

PubMed

Li, Yanfeng; Wang, Fuli; Hu, Pin; Fan, Jiadong; Han, Yishi; Liu, Bin; Liu, Tao; Yang, Chunhao; Gu, Xiangmin

2016-01-01

Osteotome sinus floor elevation is a less invasive approach to augment an insufficient alveolar bone at the posterior maxilla for dental implantation. However, this approach has some limitations due to the lack of sinus lift tools available for clinical use and the small transcrestal access to the maxillary sinus floor. We recently invented shape-memory Ni/Ti alloy wire containing tube elevators for transcrestal detaching maxillary sinus mucosa, and developed goat ex vivo models for direct visualizing the effectiveness of detaching sinus mucosa in real time during transcrestal maxillary sinus floor elevation. We evaluated our invented elevators, namely elevator 012 and elevator 014, for their effectiveness for transcrestal detaching maxillary sinus mucosa using the goat ex vivo models. We measured the length of sinus mucosa detached in mesial and distal directions or buccal and palatal directions, and the space volume created by detaching maxillary sinus mucosa in mesial, distal, buccal and palatal directions using the invented elevators. Elevator 012 had a shape-memory Ni/Ti alloy wire with a diameter of 0.012 inch, while elevator 014 had its shape-memory Ni/Ti alloy wire with a diameter of 0.014 inch. Elevator 012 could detach the goat maxillary sinus mucosa in the mesial or distal direction for 12.1±4.3 mm, while in the buccal or palatal direction for 12.5±6.7 mm. The elevator 014 could detach the goat maxillary sinus mucosa for 23.0±4.9 mm in the mesial or distal direction, and for 19.0±8.1 mm in the buccal or palatal direction. An average space volume of 1.7936±0.2079 ml was created after detaching the goat maxillay sinus mucosa in both mesial/distal direction and buccal/palatal direction using elevator 012; while the average space volume created using elevator 014 was 1.8764±0.2366 ml. Both two newly invented tube elevators could effectively detach the maxillary sinus mucosa on the goat ex vivo sinus models. Moreover, elevator 014 has advantages over the elevator 012 for the capability to detach sinus mucosa. © 2016 The Author(s) Published by S. Karger AG, Basel.

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

PubMed Central

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

2009-01-01

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

Marker-free registration for the accurate integration of CT images and the subject's anatomy during navigation surgery of the maxillary sinus

PubMed Central

Kang, S-H; Kim, M-K; Kim, J-H; Park, H-K; Park, W

2012-01-01

Objective This study compared three marker-free registration methods that are applicable to a navigation system that can be used for maxillary sinus surgery, and evaluated the associated errors, with the aim of determining which registration method is the most applicable for operations that require accurate navigation. Methods The CT digital imaging and communications in medicine (DICOM) data of ten maxillary models in DICOM files were converted into stereolithography file format. All of the ten maxillofacial models were scanned three dimensionally using a light-based three-dimensional scanner. The methods applied for registration of the maxillofacial models utilized the tooth cusp, bony landmarks and maxillary sinus anterior wall area. The errors during registration were compared between the groups. Results There were differences between the three registration methods in the zygoma, sinus posterior wall, molar alveolar, premolar alveolar, lateral nasal aperture and the infraorbital areas. The error was smallest using the overlay method for the anterior wall of the maxillary sinus, and the difference was statistically significant. Conclusion The navigation error can be minimized by conducting registration using the anterior wall of the maxillary sinus during image-guided surgery of the maxillary sinus. PMID:22499127

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

PubMed Central

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

2016-01-01

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

CT-based manual segmentation and evaluation of paranasal sinuses.

PubMed

Pirner, S; Tingelhoff, K; Wagner, I; Westphal, R; Rilk, M; Wahl, F M; Bootz, F; Eichhorn, Klaus W G

2009-04-01

Manual segmentation of computed tomography (CT) datasets was performed for robot-assisted endoscope movement during functional endoscopic sinus surgery (FESS). Segmented 3D models are needed for the robots' workspace definition. A total of 50 preselected CT datasets were each segmented in 150-200 coronal slices with 24 landmarks being set. Three different colors for segmentation represent diverse risk areas. Extension and volumetric measurements were performed. Three-dimensional reconstruction was generated after segmentation. Manual segmentation took 8-10 h for each CT dataset. The mean volumes were: right maxillary sinus 17.4 cm(3), left side 17.9 cm(3), right frontal sinus 4.2 cm(3), left side 4.0 cm(3), total frontal sinuses 7.9 cm(3), sphenoid sinus right side 5.3 cm(3), left side 5.5 cm(3), total sphenoid sinus volume 11.2 cm(3). Our manually segmented 3D-models present the patient's individual anatomy with a special focus on structures in danger according to the diverse colored risk areas. For safe robot assistance, the high-accuracy models represent an average of the population for anatomical variations, extension and volumetric measurements. They can be used as a database for automatic model-based segmentation. None of the segmentation methods so far described provide risk segmentation. The robot's maximum distance to the segmented border can be adjusted according to the differently colored areas.

Ghrelin inhibits atherosclerotic plaque angiogenesis and promotes plaque stability in a rabbit atherosclerotic model.

PubMed

Wang, Li; Chen, Qingwei; Ke, Dazhi; Li, Guiqiong

2017-04-01

Intraplaque angiogenesis associates with the instability of atherosclerotic plaques. In the present study, we investigated the effects of ghrelin on intraplaque angiogenesis and plaque instability in a rabbit model of atherosclerosis. The rabbits were randomly divided into three groups, namely, the control group, atherosclerotic model group, and ghrelin-treated group, with treatments lasting for 4 weeks. We found that the thickness ratio of the intima to media in rabbits of the ghrelin-treated group was significantly lower than that in rabbits of the atherosclerotic model group. The number of neovessels and the levels of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR2) decreased dramatically in rabbits of the ghrelin-treated group compared to those of the atherosclerotic model group. Ghrelin significantly decreased the plaque content of macrophages, matrix metalloproteinase (MMP)-2, and MMP-9, in a rabbit model of atherosclerosis. In addition, the level of the pro-inflammatory factor monocyte chemoattractant protein (MCP)-1 was significantly lower in rabbits of the ghrelin-treated group than in rabbits of the atherosclerotic model group. In summary, ghrelin can inhibit intraplaque angiogenesis and promote plaque stability by down-regulating VEGF and VEGFR2 expression, inhibiting the plaque content of macrophages, and reducing MCP-1 expression at an advanced stage of atherosclerosis in rabbits. Copyright © 2017 Elsevier Inc. All rights reserved.

Sympathetic restraint of respiratory sinus arrhythmia: implications for vagal-cardiac tone assessment in humans

NASA Technical Reports Server (NTRS)

Taylor, J. A.; Myers, C. W.; Halliwill, J. R.; Seidel, H.; Eckberg, D. L.

2001-01-01

Clinicians and experimentalists routinely estimate vagal-cardiac nerve traffic from respiratory sinus arrhythmia. However, evidence suggests that sympathetic mechanisms may also modulate respiratory sinus arrhythmia. Our study examined modulation of respiratory sinus arrhythmia by sympathetic outflow. We measured R-R interval spectral power in 10 volunteers that breathed sequentially at 13 frequencies, from 15 to 3 breaths/min, before and after beta-adrenergic blockade. We fitted changes of respiratory frequency R-R interval spectral power with a damped oscillator model: frequency-dependent oscillations with a resonant frequency, generated by driving forces and modified by damping influences. beta-Adrenergic blockade enhanced respiratory sinus arrhythmia at all frequencies (at some, fourfold). The damped oscillator model fit experimental data well (39 of 40 ramps; r = 0.86 +/- 0.02). beta-Adrenergic blockade increased respiratory sinus arrhythmia by amplifying respiration-related driving forces (P < 0.05), without altering resonant frequency or damping influences. Both spectral power data and the damped oscillator model indicate that cardiac sympathetic outflow markedly reduces heart period oscillations at all frequencies. This challenges the notion that respiratory sinus arrhythmia is mediated simply by vagal-cardiac nerve activity. These results have important implications for clinical and experimental estimation of human vagal cardiac tone.

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

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

Asgharian, Bahman; Price, Owen; Kabilan, Senthil

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

Three-dimensional sinus imaging as an adjunct to two-dimensional imaging to accelerate education and improve spatial orientation.

PubMed

Yao, William C; Regone, Rachel M; Huyhn, Nancy; Butler, E Brian; Takashima, Masayoshi

2014-03-01

Develop a novel three-dimensional (3-D) anatomical model to assist in improving spatial knowledge of the skull base, paranasal sinuses, and adjacent structures, and validate the utilization of 3-D reconstruction to augment two-dimensional (2-D) computed tomography (CT) for the training of medical students and otolaryngology-head and neck surgery residents. Prospective study. A study of 18 subjects studying sinus anatomy was conducted at a tertiary academic center during the 2011 to 2012 academic year. An image processing and 3-D modeling program was used to create a color coded 3-D scalable/layerable/rotatable model of key paranasal and skull base structures from a 2-D high-resolution sinus CT scan. Subjects received instruction of the sinus anatomy in two sessions, first through review of a 2-D CT sinus scan, followed by an educational module of the 3-D reconstruction. After each session, subjects rated their knowledge of the sinus and adjacent structures on a self-assessment questionnaire. Significant improvement in the perceived understanding of the anatomy was noted after the 3-D educational module session when compared to the 2-D CT session alone (P < .01). Every subject believed the addition of 3-D imaging accelerated their education of sinus anatomy and recommended its use to others. The impression of the learners was that a 3-D educational module, highlighting key structures, is a highly effective tool to enhance the education of medical students and otolaryngology residents in sinus and skull base anatomy and its adjacent structures, specifically in conceptualizing the spatial orientation of these structures. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

Airflow and temperature distribution inside the maxillary sinus: a computational fluid dynamics simulation.

PubMed

Zang, Hongrui; Liu, Yingxi; Han, Demin; Zhang, Luo; Wang, Tong; Sun, Xiuzhen; Li, Lifeng

2012-06-01

The airflow velocity and flux in maxillary sinuses were much lower than those in the nasal cavity, and the temperature in maxillary sinuses was much higher than the temperature in the middle meatus. With the increase of maximum diameter of the ostium, the above indices changed little. The purpose of the paper was to investigate, first, the flow and temperature distribution inside normal maxillary sinus in inspiration, and second, flow and temperature alteration with the increase of maximum ostium diameter. Three-dimensional models with nasal cavities and bilateral maxillary sinuses were constructed for computational fluid dynamics analysis. Virtual surgeries were implemented for the maxillary ostium, the maximum diameters of which were 8, 10, 12, and 15 mm, respectively. The finite volume method was used for numerical simulation. The indices of velocity, pressure, vector, and temperature were processed and compared between models. The airflow velocity in maxillary sinuses (average velocity 0.062 m/s) was much lower than that in the middle meatus (average velocity 3.26 m/s). With the increase of ostium diameter, airflow characteristics distributed in the maxillary sinuses changed little. The normal temperature in the maxillary sinus remained almost constant at 34°C and changed little with the increase of ostium diameter.

[Shock shape representation of sinus heart rate based on cloud model].

PubMed

Yin, Wenfeng; Zhao, Jie; Chen, Tiantian; Zhang, Junjian; Zhang, Chunyou; Li, Dapeng; An, Baijing

2014-04-01

The present paper is to analyze the trend of sinus heart rate RR interphase sequence after a single ventricular premature beat and to compare it with the two parameters, turbulence onset (TO) and turbulence slope (TS). Based on the acquisition of sinus rhythm concussion sample, we in this paper use a piecewise linearization method to extract its linear characteristics, following which we describe shock form with natural language through cloud model. In the process of acquisition, we use the exponential smoothing method to forecast the position where QRS wave may appear to assist QRS wave detection, and use template to judge whether current cardiac is sinus rhythm. And we choose some signals from MIT-BIH Arrhythmia Database to detect whether the algorithm is effective in Matlab. The results show that our method can correctly detect the changing trend of sinus heart rate. The proposed method can achieve real-time detection of sinus rhythm shocks, which is simple and easily implemented, so that it is effective as a supplementary method.

Simultaneous encoding of carotid sinus pressure and dP/dt by NTS target neurons of myelinated baroreceptors.

PubMed

Rogers, R F; Rose, W C; Schwaber, J S

1996-10-01

1. We seek to understand the baroreceptor signal processing that occurs centrally, beginning with the transformation of the signal at the first stage of processing. Because quantitative descriptions of the encoding of mean arterial pressure and its derivative with respect to time by baroreceptive second-order neurons have been unavailable, we characterized the responses of nucleus tractus solitarius (NTS) neurons that receive direct myelinated baroreceptor inputs to combinations of these two stimulus variables. 2. In anesthetized, paralyzed, artificially ventilated rabbits, the carotid sinus was vascularly isolated and the carotid sinus nerve was dissected free from surrounding tissue. Single-unit extracellular recordings were made from NTS neurons that received direct (with the use of physiological criteria) synaptic inputs from carotid sinus baroreceptors with myelinated axons. The vast majority of these neurons did not receive ipsilateral aortic nerve convergent inputs. With the use of a computer-controlled linear motor, a piecewise linear pressure waveform containing 32 combinations of pressure and its rate of change with respect to time (dP/dt) was delivered to the ipsilateral carotid sinus. 3. The average NTS firing frequency during the different stimulus combinations of pressure and dP/dt was a nonlinear and interdependent function of both variables. Most notable was the "extinctive" encoding of carotid sinus pressure by these neurons. This was characterized by an increase in firing frequency going from low to medium mean pressures (analyzed at certain positive dP/dt values) followed by a decrease in activity during high-pressure stimuli. All second-order neurons analyzed had their maximal firing rates when dP/dt was positive. 4. All neurons had their maximal firing frequency locations ("receptive field centers") at just 3 of 32 possible pressure-dP/dt coordinates. The responses of a small population of neurons were used to generate a composite description of the encoding of pressure and dP/dt. When combined as a composite of individually normalized values, the encoding of carotid sinus pressure and dP/dt may be approximated with the use of two-dimensional Gaussian functions. 5. We conclude that the population of NTS neurons recorded most faithfully encodes the rate and direction of (mean) pressure change, as opposed to providing the CNS with an unambiguous encoding of absolute pressure. Instead, the activity of these neurons, individually or as a population, serves as an estimate for the first derivative of the myelinated baroreceptor signal's encoding of mean pressure. We therefore speculate that the output of these individual neurons is useful in dynamic, rather than static, arterial pressure control.

Comparing maximum rate and sustainability of pacing by mechanical vs. electrical stimulation in the Langendorff-perfused rabbit heart.

PubMed

Quinn, T Alexander; Kohl, Peter

2016-12-01

Mechanical stimulation (MS) represents a readily available, non-invasive means of pacing the asystolic or bradycardic heart in patients, but benefits of MS at higher heart rates are unclear. Our aim was to assess the maximum rate and sustainability of excitation by MS vs. electrical stimulation (ES) in the isolated heart under normal physiological conditions. Trains of local MS or ES at rates exceeding intrinsic sinus rhythm (overdrive pacing; lowest pacing rates 2.5±0.5 Hz) were applied to the same mid-left ventricular free-wall site on the epicardium of Langendorff-perfused rabbit hearts. Stimulation rates were progressively increased, with a recovery period of normal sinus rhythm between each stimulation period. Trains of MS caused repeated focal ventricular excitation from the site of stimulation. The maximum rate at which MS achieved 1:1 capture was lower than during ES (4.2±0.2 vs. 5.9±0.2 Hz, respectively). At all overdrive pacing rates for which repetitive MS was possible, 1:1 capture was reversibly lost after a finite number of cycles, even though same-site capture by ES remained possible. The number of MS cycles until loss of capture decreased with rising stimulation rate. If interspersed with ES, the number of MS to failure of capture was lower than for MS only. In this study, we demonstrate that the maximum pacing rate at which MS can be sustained is lower than that for same-site ES in isolated heart, and that, in contrast to ES, the sustainability of successful 1:1 capture by MS is limited. The mechanism(s) of differences in MS vs. ES pacing ability, potentially important for emergency heart rhythm management, are currently unknown, thus warranting further investigation. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Cardiology.

Comparing maximum rate and sustainability of pacing by mechanical vs. electrical stimulation in the Langendorff-perfused rabbit heart

PubMed Central

Quinn, T. Alexander; Kohl, Peter

2016-01-01

Aims Mechanical stimulation (MS) represents a readily available, non-invasive means of pacing the asystolic or bradycardic heart in patients, but benefits of MS at higher heart rates are unclear. Our aim was to assess the maximum rate and sustainability of excitation by MS vs. electrical stimulation (ES) in the isolated heart under normal physiological conditions. Methods and results Trains of local MS or ES at rates exceeding intrinsic sinus rhythm (overdrive pacing; lowest pacing rates 2.5±0.5 Hz) were applied to the same mid-left ventricular free-wall site on the epicardium of Langendorff-perfused rabbit hearts. Stimulation rates were progressively increased, with a recovery period of normal sinus rhythm between each stimulation period. Trains of MS caused repeated focal ventricular excitation from the site of stimulation. The maximum rate at which MS achieved 1:1 capture was lower than during ES (4.2±0.2 vs. 5.9±0.2 Hz, respectively). At all overdrive pacing rates for which repetitive MS was possible, 1:1 capture was reversibly lost after a finite number of cycles, even though same-site capture by ES remained possible. The number of MS cycles until loss of capture decreased with rising stimulation rate. If interspersed with ES, the number of MS to failure of capture was lower than for MS only. Conclusion In this study, we demonstrate that the maximum pacing rate at which MS can be sustained is lower than that for same-site ES in isolated heart, and that, in contrast to ES, the sustainability of successful 1:1 capture by MS is limited. The mechanism(s) of differences in MS vs. ES pacing ability, potentially important for emergency heart rhythm management, are currently unknown, thus warranting further investigation. PMID:28011835

Investigation of atrial vulnerability by analysis of the sinus node EG from atrial fibrillation models using a phase synchronization method.

PubMed

Chen, Ying; Wu, Zhong; Yang, Cuiwei; Shao, Jun; Wong, Kelvin Kian Loong; Abbott, Derek

2012-09-01

Atrial fibrillation (AF) can result in life-threatening arrhythmia, and a clinically convenient means for detecting vulnerability remains elusive. We investigated atrial vulnerability by analyzing the sinus electrogram (EG) from AF animal models using a phase synchronization method. Using acetylcholine (ACh)-induced acute canine AF models (n= 4), a total of 128 electrical leads were attached to the surface of the anterior and posterior atria, and the pulmonary veins to form an electrocardiological mapping system. ACh was injected at varying concentrations with ladder-type adjustments. Sinus EGs and induced AF EGs that pertain to specific ACh concentrations were recorded.We hypothesize that the atrial vulnerability may be correlated with the Shannon entropy (SE) of the phase difference matrix that is extracted from the sinus EG. Our research suggests that the combination of SE with the synchronization method enables the sinus node EG to be analyzed and used to estimate atrial vulnerability.

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.

The effects of repetitious topical use of mitomycin C on antrostomy patency in maxillary antrostomy created rabbit model.

PubMed

Kavuzlu, Ali; Arslan, Necmi; Tastan, Eren; Islam, Ahmet; Ustun, Huseyin; Aydogan, Filiz

2011-11-01

The aim of our study was to investigate the effect of the topical use of mitomycin C (MMC) intraoperatively in single dose and intra-postoperatively in two doses on the narrowing of antrostomy in maxillary rabbit sinus antrostomies created experimentally. And also to determine the local and systemic side effects of topical MMC. With this objective, 0.6 mg/ml MMC was used to the first group at single dose and to the second group intraoperatively and on third day postoperatively in two doses topically for 5 min. After 8 weeks, although the mean area of antrostomy was larger than that in the control side in the first group, which received single dose MMC, the difference was not statistically significant (p = 0.287). The second group received two doses, and the antrostomy areas were found to be significantly larger than the controls (p = 0.05). Overall, the sides that received MMC were significantly larger (p = 0.029). From the point of histopathological examination of the tissue, it was seen that two-dose MMC increased the edema indicating inflammation and antrostomy resolved with normal respiratory tract epithelium. It was shown by measuring the blood values that nephrotoxic and myelosupressant effect of MMC occurring in systemic use did not occur with single or double dose topical use. Our results demonstrate that even if the number of cases was low, two doses of topical MMC usage prevent the narrowing of antrostomy while single dose MMC does not. And two-dose topical MMC usage does not have local and systemic side effects.

[Experimental evaluation of the role of the coronary sinus pressure in the regulation of coronary return volume via the coronary sinus. Surgical considerations in atrio-pulmonary diversion procedures].

PubMed

Fantidis, P; Fernández Ruiz, M A; Madero Jarabo, R; Moreno Granados, F; Cordovilla Zurdo, G; Sanz Galeote, E

1990-11-01

In order to find out the validity of the vascular waterfall mechanism in coronary venous circulation, the role of coronary sinus pressure in the regulation of coronary return volume via the coronary sinus is studied in healthy animals. An experimental model of pressure regulation in the coronary sinus was prepared, and aortic pressure, EKG and the cardiac output (measured by thermodilution) were recorded. The return volume via the coronary sinus was measured at coronary sinus pressure of 10 or less, 15, 20, and 25 mmHg or more, for a total of 36 determinations. Increased coronary sinus pressure did not produce significant changes in aortic pressure, heart rate, cardiac index or coronary return volume via coronary sinus. When coronary sinus pressure was 25 mmHg or more, there was a significant decline in the average of coronary return volume via coronary sinus. Nevertheless, stepwise variant regression showed that the coronary sinus pressure per se does not condition the volume of coronary return via the coronary sinus. Our results suggest that in the healthy animals, the vascular waterfall mechanism in coronary venous circulation is not valid. Our results suggest that in the correction of congenital cardiac malformations using atriopulmonary anastomosis procedures, employing techniques that ensure coronary sinus drainage into the left atrium, in order to avoid the hemodynamic repercussions attributable to the vascular waterfall mechanism, is not justified.

The rabbit as a model for studying lung disease and stem cell therapy.

PubMed

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

2013-01-01

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

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

PubMed Central

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

2013-01-01

No single animal model can reproduce all of the human features of both acute and chronic lung diseases. However, the rabbit is a reliable model and clinically relevant facsimile of human disease. The similarities between rabbits and humans in terms of airway anatomy and responses to inflammatory mediators highlight the value of this species in the investigation of lung disease pathophysiology and in the development of therapeutic agents. The inflammatory responses shown by the rabbit model, especially in the case of asthma, are comparable with those that occur in humans. The allergic rabbit model has been used extensively in drug screening tests, and this model and humans appear to be sensitive to similar drugs. In addition, recent studies have shown that the rabbit serves as a good platform for cell delivery for the purpose of stem-cell-based therapy. PMID:23653896

Modeling low-dose mortality and disease incubation period of inhalational anthrax in the rabbit.

PubMed

Gutting, Bradford W; Marchette, David; Sherwood, Robert; Andrews, George A; Director-Myska, Alison; Channel, Stephen R; Wolfe, Daniel; Berger, Alan E; Mackie, Ryan S; Watson, Brent J; Rukhin, Andrey

2013-07-21

There is a need to advance our ability to conduct credible human risk assessments for inhalational anthrax associated with exposure to a low number of bacteria. Combining animal data with computational models of disease will be central in the low-dose and cross-species extrapolations required in achieving this goal. The objective of the current work was to apply and advance the competing risks (CR) computational model of inhalational anthrax where data was collected from NZW rabbits exposed to aerosols of Ames strain Bacillus anthracis. An initial aim was to parameterize the CR model using high-dose rabbit data and then conduct a low-dose extrapolation. The CR low-dose attack rate was then compared against known low-dose rabbit data as well as the low-dose curve obtained when the entire rabbit dose-response data set was fitted to an exponential dose-response (EDR) model. The CR model predictions demonstrated excellent agreement with actual low-dose rabbit data. We next used a modified CR model (MCR) to examine disease incubation period (the time to reach a fever >40 °C). The MCR model predicted a germination period of 14.5h following exposure to a low spore dose, which was confirmed by monitoring spore germination in the rabbit lung using PCR, and predicted a low-dose disease incubation period in the rabbit between 14.7 and 16.8 days. Overall, the CR and MCR model appeared to describe rabbit inhalational anthrax well. These results are discussed in the context of conducting laboratory studies in other relevant animal models, combining the CR/MCR model with other computation models of inhalational anthrax, and using the resulting information towards extrapolating a low-dose response prediction for man. Published by Elsevier Ltd.

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.

[Comparative experiments of stripping sheep maxillary sinus mucosal with new-type stripper and umbrella detacher].

PubMed

Jiadong, Fan; Yanfeng, Li; Le, Liu; Yishi, Han; Pin, Hu; Yue, Zhang; Wenya, Bao

2016-10-01

To compare the stripping length obtained through the model of 0.012 and 0.014 of the nickel-titanium dual-stage maxillary sinus mucosa stripper, and the umbrella detacher. Twenty-four goats (1.5-2 years old) were chosen, randomly divided into A, B, C groups, each group of eight. Group A was 0.012 model group, group B was 0.014 model group, group C was umbrella detacher group. Animal model was established, and maxillary sinus mucosa was stripped to the left and right sides of the bottom of the sinus in three groups. The data was measured when stripping to the limit or being perforated. The average length of group A was 12.41 mm±4.35 mm, two cases perforated. The average length of group B was 23.38 mm±4.84 mm, one case perforated. The average length of group C was 2.61 mm±0.30 mm. The population mean of stripping length in three groups was not all the same calculated by analysis of variance (P<0.01). There were significant differences in the stripping length of the three groups by the SNK test (P<0.05). The nickel-titanium dual-stage maxillary sinus mucosa stripper can achieve a larger mucosal stripping range. The stripper with a model of 0.014 has a moderate flexibility and safety, and it can strip a large area of sinus mucosa.
.

Improvement of aortic valve stenosis by ApoA-I mimetic therapy is associated with decreased aortic root and valve remodelling in mice

PubMed Central

Trapeaux, J; Busseuil, D; Shi, Y; Nobari, S; Shustik, D; Mecteau, M; El-Hamamsy, I; Lebel, M; Mongrain, R; Rhéaume, E; Tardif, J-C

2013-01-01

Background and Purpose We have shown that infusions of apolipoprotein A-I (ApoA-I) mimetic peptide induced regression of aortic valve stenosis (AVS) in rabbits. This study aimed at determining the effects of ApoA-I mimetic therapy in mice with calcific or fibrotic AVS. Experimental Approach Apolipoprotein E-deficient (ApoE−/−) mice and mice with Werner progeria gene deletion (WrnΔhel/Δhel) received high-fat diets for 20 weeks. After developing AVS, mice were randomized to receive saline (placebo group) or ApoA-I mimetic peptide infusions (ApoA-I treated groups, 100 mg·kg−1 for ApoE−/− mice; 50 mg·kg−1 for Wrn mice), three times per week for 4 weeks. We evaluated effects on AVS using serial echocardiograms and valve histology. Key Results Aortic valve area (AVA) increased in both ApoE−/− and Wrn mice treated with the ApoA-I mimetic compared with placebo. Maximal sinus wall thickness was lower in ApoA-I treated ApoE−/− mice. The type I/III collagen ratio was lower in the sinus wall of ApoA-I treated ApoE−/− mice compared with placebo. Total collagen content was reduced in aortic valves of ApoA-I treated Wrn mice. Our 3D computer model and numerical simulations confirmed that the reduction in aortic root wall thickness resulted in improved AVA. Conclusions and Implications ApoA-I mimetic treatment reduced AVS by decreasing remodelling and fibrosis of the aortic root and valve in mice. PMID:23638718

Modified three-dimensional skull base model with artificial dura mater, cranial nerves, and venous sinuses for training in skull base surgery: technical note.

PubMed

Mori, Kentaro; Yamamoto, Takuji; Oyama, Kazutaka; Ueno, Hideaki; Nakao, Yasuaki; Honma, Keiichirou

2008-12-01

Experience with dissection of the cavernous sinus and the temporal bone is essential for training in skull base surgery, but the opportunities for cadaver dissection are very limited. A modification of a commercially available prototype three-dimensional (3D) skull base model, made by a selective laser sintering method and incorporating surface details and inner bony structures such as the inner ear structures and air cells, is proposed to include artificial dura mater, cranial nerves, venous sinuses, and the internal carotid artery for such surgical training. The transpetrosal approach and epidural cavernous sinus surgery (Dolenc's technique) were performed on this modified model using a high speed drill or ultrasonic bone curette under an operating microscope. The model could be dissected in almost the same way as a real cadaver. The modified 3D skull base model provides a good educational tool for training in skull base surgery.

TRPM4 non-selective cation channels influence action potentials in rabbit Purkinje fibres.

PubMed

Hof, Thomas; Sallé, Laurent; Coulbault, Laurent; Richer, Romain; Alexandre, Joachim; Rouet, René; Manrique, Alain; Guinamard, Romain

2016-01-15

The transient receptor potential melastatin 4 (TRPM4) inhibitor 9-phenanthrol reduces action potential duration in rabbit Purkinje fibres but not in ventricle. TRPM4-like single channel activity is observed in isolated rabbit Purkinje cells but not in ventricular cells. The TRPM4-like current develops during the notch and early repolarization phases of the action potential in Purkinje cells. Transient receptor potential melastatin 4 (TRPM4) Ca(2+)-activated non-selective cation channel activity has been recorded in cardiomyocytes and sinus node cells from mammals. In addition, TRPM4 gene mutations are associated with human diseases of cardiac conduction, suggesting that TRPM4 plays a role in this aspect of cardiac function. Here we evaluate the TRPM4 contribution to cardiac electrophysiology of Purkinje fibres. Ventricular strips with Purkinje fibres were isolated from rabbit hearts. Intracellular microelectrodes recorded Purkinje fibre activity and the TRPM4 inhibitor 9-phenanthrol was applied to unmask potential TRPM4 contributions to the action potential. 9-Phenanthrol reduced action potential duration measured at the point of 50 and 90% repolarization with an EC50 of 32.8 and 36.1×10(-6) mol l(-1), respectively, but did not modulate ventricular action potentials. Inside-out patch-clamp recordings were used to monitor TRPM4 activity in isolated Purkinje cells. TRPM4-like single channel activity (conductance = 23.8 pS; equal permeability for Na(+) and K(+); sensitivity to voltage, Ca(2+) and 9-phenanthrol) was observed in 43% of patches from Purkinje cells but not from ventricular cells (0/16). Action potential clamp experiments performed in the whole-cell configuration revealed a transient inward 9-phenanthrol-sensitive current (peak density = -0.65 ± 0.15 pA pF(-1); n = 5) during the plateau phases of the Purkinje fibre action potential. These results show that TRPM4 influences action potential characteristics in rabbit Purkinje fibres and thus could modulate cardiac conduction and be involved in triggering arrhythmias. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

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 human FE models of bone, where, unlike rabbit tibia, the model would be relatively insensitive to very small changes in load position. However, the rabbit model itself is less beneficial as a tool to understand the mechanical behaviour of TSFs in humans due to the small size of the rabbit bone and the limitations of human-scale CT scanning equipment. The current modelling technique could be used to develop human FE models. However, the rabbit model itself has significant limitations in understanding human TSF mechanics.

Efficacy of NVC-422 against Staphylococcus aureus biofilms in a sheep biofilm model of sinusitis.

PubMed

Singhal, Deepti; Jekle, Andreas; Debabov, Dmitri; Wang, Lu; Khosrovi, Bez; Anderson, Mark; Foreman, Andrew; Wormald, Peter-John

2012-01-01

Bacterial biofilms are a major obstacle in management of recalcitrant chronic rhinosinusitis. NVC-422 is a potent, fast-acting, broad-spectrum, nonantibiotic, antimicrobial with a new mechanism of action effective against biofilm bacteria in in vitro conditions. The aim of this study was to investigate the safety and efficacy of NVC-422 as local antibiofilm treatment in a sheep model of rhinosinusitis. After accessing and occluding frontal sinus ostia in 24 merino sheep via staged endoscopic procedures, S. aureus clinical isolate was instilled in frontal sinuses. Following biofilm formation, ostial obstruction was removed and sinuses irrigated with 0.1% and 0.5% NVC-422 in 5 mM acetate isotonic saline at pH 4.0. Sheep were monitored for adverse effects and euthanized 24 hours after treatment. Frontal sinuses were assessed for infection and changes in mucosa after the treatment. S. aureus biofilms were identified with Baclight-confocal scanning microscopy protocol and the biofilm biomass assayed by applying the COMSTAT2 program to recorded image stacks. After 2 irrigations with 0.1% NVC-422, S. aureus biofilm biomass was reduced when compared to control sinuses (p = 0.0001), though this effect was variable in samples. NVC-422 0.5% solution irrigations reduced biofilm even more significantly and consistently over all samples (p < 0.0001). NVC-422 0.5% was also more effective than 0.1% NVC-422, vehicle control, and normal saline sinus irrigations in reducing biofilm biomass (p < 0.05 for all subgroups). No adverse events were observed in sheep after sinus irrigations with 0.1% and 0.5% NVC-422 solutions. NVC-422 is an effective topical agent against S. aureus biofilms, with dose-dependent efficacy in this animal model of biofilm-associated sinusitis. Copyright © 2012 American Rhinologic Society-American Academy of Otolaryngic Allergy, LLC.

Monte Carlo modeling of light propagation in the human head for applications in sinus imaging

NASA Astrophysics Data System (ADS)

Cerussi, Albert E.; Mishra, Nikhil; You, Joon; Bhandarkar, Naveen; Wong, Brian J. F.

2015-02-01

Sinus blockages are a common reason for physician visits, affecting 1 out of 7 in the United States. Over 20 million cases of acute bacterial sinusitis become chronic and require medical treatment. Diagnosis in the primary care setting is challenging because symptom criteria (via detailed clinical history) plus objective imaging (CT or endoscopy) is recommended. Unfortunately, neither option is routinely available in primary care. Our previous work demonstrated that low-cost near infrared (NIR) transillumination instruments produced signals that correlated with the bulk findings of sinus opacity measured by CT. We have upgraded the technology, but questions remain such as finding the optimal arrangement of light sources, measuring the influence of specific anatomical structures, and determining detection limits. In order to begin addressing these questions, we have modeled NIR light propagation inside the adult human head using a mesh-based Monte Carlo algorithm (MMCLab) applied to a detailed anatomical head model constructed from CT images. In this application the sinus itself, which under healthy conditions is a void region (e.g., non-scattering), is the region of interest instead of an obstacle to other contrast mechanisms. We report preliminary simulations that characterize the changes in detected intensity due to clear (i.e., healthy) versus blocked sinuses. We also ran simulations for two of our clinical cases and compared results with the measurements. The simulations presented herein serve as a proof of concept that this approach could be used to understand contrast mechanisms and limitations of NIR imaging of the sinus cavities.

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

PubMed

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

2018-05-01

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

Systematic evaluation of a tissue-engineered bone for maxillary sinus augmentation in large animal canine model.

PubMed

Wang, Shaoyi; Zhang, Zhiyuan; Xia, Lunguo; Zhao, Jun; Sun, Xiaojuan; Zhang, Xiuli; Ye, Dongxia; Uludağ, Hasan; Jiang, Xinquan

2010-01-01

The objective of this study is to systematically evaluate the effects of a tissue-engineered bone complex for maxillary sinus augmentation in a canine model. Twelve sinus floor augmentation surgeries in 6 animals were performed bilaterally and randomly repaired with the following 3 groups of grafts: group A consisted of tissue-engineered osteoblasts/beta-TCP complex (n=4); group B consisted of beta-TCP alone (n=4); group C consisted of autogenous bone obtained from iliac crest as a positive control (n=4). All dogs had uneventful healings following the surgery. Sequential polychrome fluorescent labeling, maxillofacial CT, microhardness tests, as well as histological and histomorphometric analyses indicated that the tissue-engineered osteoblasts/beta-TCP complex dramatically promoted bone formation and mineralization and maximally maintained the height and volume of elevated maxillary sinus. By comparison, both control groups of beta-TCP or autologous iliac bone showed considerable resorption and replacement by fibrous or fatty tissue. We thus conclude that beta-TCP alone could barely maintain the height and volume of the elevated sinus floor, and that the transplantation of autogenous osteoblasts on beta-TCP could promote earlier bone formation and mineralization, maximally maintain height, volume and increase the compressive strength of augmented maxillary sinus. This tissue engineered bone complex might be a better alternative to autologous bone for the clinical edentulous maxillary sinus augmentation. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Retinal Remodeling in the Tg P347L Rabbit, a Large-Eye Model of Retinal Degeneration

PubMed Central

Jones, Bryan William; Kondo, Mineo; Terasaki, Hiroko; Watt, Carl Brock; Rapp, Kevin; Anderson, James; Lin, Yanhua; Shaw, Marguerite Victoria; Yang, Jia-Hui; Marc, Robert Edward

2013-01-01

Retinitis pigmentosa (RP) is an inherited blinding disease characterized by progressive loss of retinal photo-receptors. There are numerous rodent models of retinal degeneration, but most are poor platforms for interventions that will translate into clinical practice. The rabbit possesses a number of desirable qualities for a model of retinal disease including a large eye and an existing and substantial knowledge base in retinal circuitry, anatomy, and ophthalmology. We have analyzed degeneration, remodeling, and reprogramming in a rabbit model of retinal degeneration, expressing a rhodopsin proline 347 to leucine transgene in a TgP347L rabbit as a powerful model to study the pathophysiology and treatment of retinal degeneration. We show that disease progression in the TgP347L rabbit closely tracks human cone-sparing RP, including the cone-associated preservation of bipolar cell signaling and triggering of reprogramming. The relatively fast disease progression makes the TgP347L rabbit an excellent model for gene therapy, cell biological intervention, progenitor cell transplantation, surgical interventions, and bionic prosthetic studies. PMID:21681749

Simultaneous sinus lift and implantation using platelet-rich fibrin as sole grafting material.

PubMed

Jeong, Seung-Mi; Lee, Chun-Ui; Son, Jeong-Seog; Oh, Ji-Hyeon; Fang, Yiqin; Choi, Byung-Ho

2014-09-01

Recently, several authors have shown that simultaneous sinus lift and implantation using autologous platelet-rich fibrin as the sole filling material is a reliable procedure promoting bone augmentation in the maxillary sinus. The aim of this study was to examine the effect of simultaneous sinus lift and implantation using platelet-rich fibrin as the sole grafting material on bone formation in a canine sinus model. An implant was placed after sinus membrane elevation in the maxillary sinus of six adult female mongrel dogs. The resulting space between the membrane and sinus floor was filled with autologous platelet-rich fibrin retrieved from each dog. The implants were left in place for six months. Bone tissue was seen at the lower part of the implants introduced into the sinus cavity. The height of the newly formed bone around the implants ranged from 0 mm to 4.9 mm (mean; 2.6 ± 2.0 mm) on the buccal side and from 0 mm to 4.2 mm (mean; 1.3 ± 1.8 mm) on the palatal side. The findings from this study suggest that simultaneous sinus lift and implantation using platelet-rich fibrin as sole grafting material is not a predictable and reproducible procedure, especially with respect to the bone formation around the implants in the sinus cavity. Copyright © 2014 European Association for Cranio-Maxillo-Facial Surgery. All rights reserved.

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.

Membrane currents underlying activity in frog sinus venosus

PubMed Central

Brown, Hilary F.; Giles, Wayne; Noble, Susan J.

1977-01-01

1. The spontaneous electrical activity of small strips of muscle from the sinus venosus region of the heart of Rana catesbeiana was investigated using the double sucrose gap technique. The voltage clamp was used to record the ionic currents underlying the pace-maker depolarization and the action potential. 2. The records of spontaneous electrical activity are very similar to those obtained from the sinus venosus using micro-electrodes. Moreover, the pace-maker activity is almost completely insensitive to tetrodotoxin (TTX) at 2·0 × 10-6 g/ml., which suggests that the pace-maker responses can be classified as primary, as opposed to follower pacing. 3. In response to short rectangular depolarizing voltage clamp pulses, only one inward current is activated. This current is almost completely insensitive to TTX but can be blocked by manganese ions. It appears, therefore, to be equivalent to the slow inward (Ca2+/Na+) current, Isi, of other cardiac tissues. The threshold for Isi is near to the maximum diastolic potential, indicating that it must be activated during the pace-maker depolarization. 4. Interruption of the normal pace-maker depolarization by rapid activation of the voltage clamp circuit reveals the time-dependent decay of outward current. This current reverses between -75 and -90 mV and, therefore, is probably carried mainly by potassium ions. 5. Outward current decay is not a simple exponential, and Hodgkin—Huxley analysis suggests that two distinct components of outward current may be present. One of these is activated in the potential range of the pace-maker depolarization and the other at more positive potentials. Both outward currents reach full, steady-state activation at about zero mV, i.e. within the `plateau' range of the sinus action potential. 6. These results are compared with other recently published voltage clamp data from the rabbit sino—atrial node. 7. A hypothesis for the generation of pace-maker activity is presented which involves (i) decay of outward current and (ii) activation of the slow inward current, Isi. PMID:303699

Distribution of Electromechanical Delay in the Heart: Insights from a Three-Dimensional Electromechanical Model

PubMed Central

Gurev, V.; Constantino, J.; Rice, J.J.; Trayanova, N.A.

2010-01-01

In the intact heart, the distribution of electromechanical delay (EMD), the time interval between local depolarization and myocyte shortening onset, depends on the loading conditions. The distribution of EMD throughout the heart remains, however, unknown because current experimental techniques are unable to evaluate three-dimensional cardiac electromechanical behavior. The goal of this study was to determine the three-dimensional EMD distributions in the intact ventricles for sinus rhythm (SR) and epicardial pacing (EP) by using a new, to our knowledge, electromechanical model of the rabbit ventricles that incorporates a biophysical representation of myofilament dynamics. Furthermore, we aimed to ascertain the mechanisms that underlie the specific three-dimensional EMD distributions. The results revealed that under both conditions, the three-dimensional EMD distribution is nonuniform. During SR, EMD is longer at the epicardium than at the endocardium, and is greater near the base than at the apex. After EP, the three-dimensional EMD distribution is markedly different; it also changes with the pacing rate. For both SR and EP, late-depolarized regions were characterized with significant myofiber prestretch caused by the contraction of the early-depolarized regions. This prestretch delays myofiber-shortening onset, and results in a longer EMD, giving rise to heterogeneous three-dimensional EMD distributions. PMID:20682251

Endoscopic sinus surgery dissection courses using a real simulator: the benefits of this training.

PubMed

Fortes, Bibiana; Balsalobre, Leonardo; Weber, Raimar; Stamm, Raquel; Stamm, Aldo; Oto, Fernando; Coronel, Nathália

2016-01-01

Endonasal surgeries are among the most common procedures performed in otolaryngology. Due to difficulty in cadaver acquisition and the intrinsic risks of training residents during operations on real patients, nasosinusal endoscopic dissection courses utilizing real simulators, such as the Sinus Model Otorhino Neuro Trainer are being developed as a new technique to facilitate the acquisition of better anatomical knowledge and surgical skill. To evaluate the efficacy of nasosinusal endoscopic dissection courses with the Sinus Model Otorhino Neuro Trainer simulator in the training of otolaryngology surgeons. A prospective, longitudinal cohort study was conducted with 111 otolaryngologists who participated in a theoretical and practical course of endoscopic surgery dissection using the Sinus Model Otorhino Neuro Trainer simulator, with application of questionnaires during and after the course. From the ten procedures performed utilizing the simulator, the evaluation revealed mean scores from 3.1 to 4.1 (maximum of 5). Seventy-seven participants answered the questionnaire six months after the end of the course. 93% of them reported that they could perform the procedures more safely following the course, 98% reported an improvement in their anatomical and clinical knowledge, and 85% related an improvement in their surgical ability. After the course, the number of endoscopic surgeries increased in 40% of the respondents. Endoscopic sinus dissection courses using the Sinus Model Otorhino Neuro Trainer simulator proved to be useful in the training of otolaryngologists. Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

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

DTIC Science & Technology

2017-10-22

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

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

PubMed

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

2016-02-06

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

``Magical'' fluid pathways: inspired airflow corridors for optimal drug delivery to human sinuses

NASA Astrophysics Data System (ADS)

Basu, Saikat; Farzal, Zainab; Kimbell, Julia S.

2017-11-01

Topical delivery methods like nasal sprays are an important therapeutic component for sinusitis (inflammation and clogging of the paranasal sinuses). The sinuses are air-filled sacs, identified as: maxillaries (under the eyes and deep to cheeks bilaterally; largest in volume), frontals (above and medial to the eyes, behind forehead area), ethmoids (between the eyes, inferior to the frontal sinuses), and sphenoids (superior and posterior to ethmoids). We develop anatomic CT-based 3D reconstructions of the human nasal cavity for multiple subjects. Through CFD simulations on Fluent for measured breathing rates, we track inspiratory airflow in all the models and the corresponding sprayed drug transport (for a commercially available sprayer, with experimentally tested particle size distributions). The protocol is implemented for a wide array of spray release points. We make the striking observation that the same release points in each subject provide better particle deposition in all the sinuses, despite the sinuses being located at different portions of the nasal cavity. This leads to the conjecture that the complicated anatomy-based flow physics artifacts in the nasal canal generate certain ``magical'' streamlines, providing passage for improved drug transport to all sinus targets. Supported by NIH Grant R01 HL122154.

A novel experimental animal model of arterial stenosis based on endovascular radiofrequency energy application.

PubMed

Lazoura, Olga; Zacharoulis, Dimitris; Kanavou, Theodora; Rountas, Christos; Katsimboulas, Michael; Tzovaras, George; Habib, Nagy

2011-01-01

To develop a new rabbit model of arterial stenosis using endovascular radiofrequency (RF) energy. Ten rabbits were used for multiple endovascular RF applications to the aorta and left common carotid artery through the Habib™ VesCoag™ catheter. Angiography and color Doppler ultrasound were used to assess vessel patency immediately following the procedure and six weeks later. One rabbit was sacrificed following the procedure for histopathologic analysis of the vessel wall. Two rabbits died of aortic and carotid rupture, respectively, immediately after the procedure. The remaining seven rabbits were sacrificed after six-week follow-up for histopathological analysis. Optimal RF generator settings to induce significant arterial stenosis (>50%) without complications were standardized at 24-26 watts (W) for 1.5 min for the aorta and 6 W for 1 min for the common carotid artery. The six-week follow-up showed permanent results in all surviving rabbits. Histopathology revealed intima and medial smooth muscle layer necrosis. We have developed a novel rabbit model of arterial stenosis using endovascular RF energy. Our model is fast, safe, inexpensive, and reproducible. It would be useful for experimental investigations and new therapeutic devices.

Monte Carlo modeling of light propagation in the human head for applications in sinus imaging

PubMed Central

Cerussi, Albert E.; Mishra, Nikhil; You, Joon; Bhandarkar, Naveen; Wong, Brian

2015-01-01

Abstract. Sinus blockages are a common reason for physician visits, affecting one out of seven people in the United States, and often require medical treatment. Diagnosis in the primary care setting is challenging because symptom criteria (via detailed clinical history) plus objective imaging [computed tomography (CT) or endoscopy] are recommended. Unfortunately, neither option is routinely available in primary care. We previously demonstrated that low-cost near-infrared (NIR) transillumination correlates with the bulk findings of sinus opacity measured by CT. We have upgraded the technology, but questions of source optimization, anatomical influence, and detection limits remain. In order to begin addressing these questions, we have modeled NIR light propagation inside a three-dimensional adult human head constructed via CT images using a mesh-based Monte Carlo algorithm (MMCLAB). In this application, the sinus itself, which when healthy is a void region (e.g., nonscattering), is the region of interest. We characterize the changes in detected intensity due to clear (i.e., healthy) versus blocked sinuses and the effect of illumination patterns. We ran simulations for two clinical cases and compared simulations with measurements. The simulations presented herein serve as a proof of concept that this approach could be used to understand contrast mechanisms and limitations of NIR sinus imaging. PMID:25781310

Monte Carlo modeling of light propagation in the human head for applications in sinus imaging

NASA Astrophysics Data System (ADS)

Cerussi, Albert E.; Mishra, Nikhil; You, Joon; Bhandarkar, Naveen; Wong, Brian

2015-03-01

Sinus blockages are a common reason for physician visits, affecting one out of seven people in the United States, and often require medical treatment. Diagnosis in the primary care setting is challenging because symptom criteria (via detailed clinical history) plus objective imaging [computed tomography (CT) or endoscopy] are recommended. Unfortunately, neither option is routinely available in primary care. We previously demonstrated that low-cost near-infrared (NIR) transillumination correlates with the bulk findings of sinus opacity measured by CT. We have upgraded the technology, but questions of source optimization, anatomical influence, and detection limits remain. In order to begin addressing these questions, we have modeled NIR light propagation inside a three-dimensional adult human head constructed via CT images using a mesh-based Monte Carlo algorithm (MMCLAB). In this application, the sinus itself, which when healthy is a void region (e.g., nonscattering), is the region of interest. We characterize the changes in detected intensity due to clear (i.e., healthy) versus blocked sinuses and the effect of illumination patterns. We ran simulations for two clinical cases and compared simulations with measurements. The simulations presented herein serve as a proof of concept that this approach could be used to understand contrast mechanisms and limitations of NIR sinus imaging.

Expression of rabbit IL-4 by recombinant myxoma viruses enhances virulence and overcomes genetic resistance to myxomatosis.

PubMed

Kerr, P J; Perkins, H D; Inglis, B; Stagg, R; McLaughlin, E; Collins, S V; Van Leeuwen, B H

2004-06-20

Rabbit IL-4 was expressed in the virulent standard laboratory strain (SLS) and the attenuated Uriarra (Ur) strain of myxoma virus with the aim of creating a Th2 cytokine environment and inhibiting the development of an antiviral cell-mediated response to myxomatosis in infected rabbits. This allowed testing of a model for genetic resistance to myxomatosis in wild rabbits that have undergone 50 years of natural selection for resistance to myxomatosis. Expression of IL-4 significantly enhanced virulence of both virulent and attenuated virus strains in susceptible (laboratory) and resistant (wild) rabbits. SLS-IL-4 completely overcame genetic resistance in wild rabbits. The pathogenesis of SLS-IL-4 was compared in susceptible and resistant rabbits. The results support a model for resistance to myxomatosis of an enhanced innate immune response controlling virus replication and allowing an effective antiviral cell-mediated immune response to develop in resistant rabbits. Expression of IL-4 did not overcome immunity to myxomatosis induced by immunization.

Strategies for Diagnosing and Treating Suspected Acute Bacterial Sinusitis

PubMed Central

Balk, Ethan M; Zucker, Deborah R; Engels, Eric A; Wong, John B; Williams, John W; Lau, Joseph

2001-01-01

OBJECTIVE Symptoms suggestive of acute bacterial sinusitis are common. Available diagnostic and treatment options generate substantial costs with uncertain benefits. We assessed the cost-effectiveness of alternative management strategies to identify the optimal approach. DESIGN For such patients, we created a Markov model to examine four strategies: 1) no antibiotic treatment; 2) empirical antibiotic treatment; 3) clinical criteria-guided treatment; and 4) radiography-guided treatment. The model simulated a 14-day course of illness, included sinusitis prevalence, antibiotic side effects, sinusitis complications, direct and indirect costs, and symptom severity. Strategies costing less than $50,000 per quality-adjusted life year gained were considered “cost-effective.” MEASUREMENTS AND MAIN RESULTS For mild or moderate disease, basing antibiotic treatment on clinical criteria was cost-effective in clinical settings where sinusitis prevalence is within the range of 15% to 93% or 3% to 63%, respectively. For severe disease, or to prevent sinusitis or antibiotic side effect symptoms, use of clinical criteria was cost-effective in settings with lower prevalence (below 51% or 44%, respectively); empirical antibiotics was cost-effective with higher prevalence. Sinus radiography-guided treatment was never cost-effective for initial treatment. CONCLUSIONS Use of a simple set of clinical criteria to guide treatment is a cost-effective strategy in most clinical settings. Empirical antibiotics are cost-effective in certain settings; however, their use results in many unnecessary prescriptions. If this resulted in increased antibiotic resistance, costs would substantially rise and efficacy would fall. Newer, expensive antibiotics are of limited value. Additional testing is not cost-effective. Further studies are needed to find an accurate, low-cost diagnostic test for acute bacterial sinusitis. PMID:11679039

The electrophysiological effects of nicotinic and electrical stimulation of intrinsic cardiac ganglia in the absence of extrinsic autonomic nerves in the rabbit heart.

PubMed

Allen, Emily; Coote, John H; Grubb, Blair D; Batten, Trevor Fc; Pauza, Dainius H; Ng, G André; Brack, Kieran E

2018-05-22

The intrinsic cardiac nervous system (ICNS) is a rich network of cardiac nerves that converge to form distinct ganglia and extend across the heart and is capable of influencing cardiac function. To provide a picture of the neurotransmitter/neuromodulator profile of the rabbit ICNS and determine the action of spatially divergent ganglia on cardiac electrophysiology. Nicotinic or electrical stimulation was applied at discrete sites of the intrinsic cardiac nerve plexus in the Langendorff perfused rabbit heart. Functional effects on sinus rate and atrioventricular conduction were measured. Immunohistochemistry for choline acetyltransferase (ChAT), tyrosine hydroxylase (TH) and/or neuronal nitric oxide synthase (nNOS) was performed on whole-mount preparations. Stimulation within all ganglia produced either bradycardia, tachycardia or a biphasic brady-tachycardia. Electrical stimulation of the right atrial (RA) and right neuronal cluster (RNC) regions produced the greatest chronotropic responses. Significant prolongation of atrioventricular conduction (AVC) was predominant at the pulmonary vein-caudal vein region (PVCV). Neurons immunoreactive (IR) only for ChAT, or TH or nNOS were consistently located within the limits of the hilum and at the roots of the right cranial and right pulmonary veins. ChAT-IR neurons were most abundant (1946±668 neurons). Neurons IR solely for nNOS were distributed within ganglia. Stimulation of intrinsic ganglia, shown to be of phenotypic complexity but predominantly of cholinergic nature, indicates that clusters of neurons are capable of independent selective effects on cardiac electrophysiology, therefore providing a potential therapeutic target for the prevention and treatment of cardiac disease. Copyright © 2018. Published by Elsevier Inc.

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

PubMed

Reichenbach, A; Baar, U

1985-08-15

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

Rabbit N-acetyltransferase 2 genotyping method to investigate role of acetylation polymorphism on N- and O-acetylation of aromatic and heterocyclic amine carcinogens.

PubMed

Hein, David W; Doll, Mark A

2017-09-01

The rabbit was the initial animal model to investigate the acetylation polymorphism expressed in humans. Use of the rabbit model is compromised by lack of a rapid non-invasive method for determining acetylator phenotype. Slow acetylator phenotype in the rabbit results from deletion of the N-acetyltransferase 2 (NAT2) gene. A relatively quick and non-invasive method for identifying the gene deletion was developed and acetylator phenotypes confirmed by measurement of N- and O-acetyltransferase activities in hepatic cytosols. Rabbit liver cytosols catalyzed the N-acetylation of sulfamethazine (p = 0.0014), benzidine (p = 0.0257), 4-aminobiphenyl (p = 0.0012), and the O-acetylation of N-hydroxy-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-OH-PhIP; p = 0.002) at rates significantly higher in rabbits possessing NAT2 gene than rabbits with NAT2 gene deleted. In contrast, hepatic cytosols catalyzed the N-acetylation of p-aminobenzoic acid (an N-acetyltransferase 1 selective substrate) at rates that did not differ significantly (p > 0.05) between rabbits positive and negative for NAT2. The new NAT2 genotyping method facilitates use of the rabbit model to investigate the role of acetylator polymorphism in the metabolism of aromatic and heterocyclic amine drugs and carcinogens.

Impaired receptor-mediated catabolism of low density lipoprotein in the WHHL rabbit, an animal model of familial hypercholesterolemia

PubMed Central

Bilheimer, David W.; Watanabe, Yoshio; Kita, Toru

1982-01-01

The homozygous WHHL (Watanabe heritable hyperlipidemic) rabbit displays either no or only minimal low density lipoprotein (LDL) receptor activity on cultured fibroblasts and liver membranes and has therefore been proposed as an animal model for human familial hypercholesterolemia. To assess the impact of this mutation on LDL metabolism in vivo, we performed lipoprotein turnover studies in normal and WHHL rabbits using both native rabbit LDL and chemically modified LDL (i.e., methyl-LDL) that does not bind to LDL receptors. The total fractional catabolic rate (FCR) for LDL in the normal rabbit was 3.5-fold greater than in the WHHL rabbit. Sixty-seven percent of the total FCR for LDL in the normal rabbit was due to LDL receptor-mediated clearance and 33% was attributable to receptor-independent processes; in the WHHL rabbit, essentially all of the LDL was catabolized via receptor-independent processes. Despite a 17.5-fold elevated plasma pool size of LDL apoprotein (apo-LDL) in WHHL as compared to normal rabbits, the receptor-independent FCR—as judged by the turnover of methyl-LDL—was similar in the two strains. Thus, the receptor-independent catabolic processes are not influenced by the mutation affecting the LDL receptor. The WHHL rabbits also exhibited a 5.6-fold increase in the absolute rate of apo-LDL synthesis and catabolism. In absolute terms, the WHHL rabbit cleared 19-fold more apo-LDL via receptor-independent processes than did the normal rabbit and cleared virtually none by the receptor-dependent pathway. These results indicate that the homozygous WHHL rabbit shares a number of metabolic features in common with human familial hypercholesterolemia and should serve as a useful model for the study of altered lipoprotein metabolism associated with receptor abnormalities. We also noted that the in vivo metabolic behavior of human and rabbit LDL in the normal rabbit differed such that the mean total FCR for human LDL was only 64% of the mean total FCR for rabbit LDL, whereas human and rabbit methyl-LDL were cleared at identical rates. Thus, if human LDL and methyl-LDL had been used in these studies, the magnitude of both the total and receptor-dependent FCR would have been underestimated. PMID:6285345

Modelling Landscape-Level Numerical Responses of Predators to Prey: The Case of Cats and Rabbits

PubMed Central

Cruz, Jennyffer; Glen, Alistair S.; Pech, Roger P.

2013-01-01

Predator-prey systems can extend over large geographical areas but empirical modelling of predator-prey dynamics has been largely limited to localised scales. This is due partly to difficulties in estimating predator and prey abundances over large areas. Collection of data at suitably large scales has been a major problem in previous studies of European rabbits (Oryctolagus cuniculus) and their predators. This applies in Western Europe, where conserving rabbits and predators such as Iberian lynx (Lynx pardinus) is important, and in other parts of the world where rabbits are an invasive species supporting populations of introduced, and sometimes native, predators. In pastoral regions of New Zealand, rabbits are the primary prey of feral cats (Felis catus) that threaten native fauna. We estimate the seasonal numerical response of cats to fluctuations in rabbit numbers in grassland–shrubland habitat across the Otago and Mackenzie regions of the South Island of New Zealand. We use spotlight counts over 1645 km of transects to estimate rabbit and cat abundances with a novel modelling approach that accounts simultaneously for environmental stochasticity, density dependence and varying detection probability. Our model suggests that cat abundance is related consistently to rabbit abundance in spring and summer, possibly through increased rabbit numbers improving the fecundity and juvenile survival of cats. Maintaining rabbits at low abundance should therefore suppress cat numbers, relieving predation pressure on native prey. Our approach provided estimates of the abundance of cats and rabbits over a large geographical area. This was made possible by repeated sampling within each season, which allows estimation of detection probabilities. A similar approach could be applied to predator-prey systems elsewhere, and could be adapted to any method of direct observation in which there is no double-counting of individuals. Reliable estimates of numerical responses are essential for managing both invasive and threatened predators and prey. PMID:24039978

Holmium: yttrium aluminum garnet laser-assisted endoscopic sinus surgery: laboratory experience.

PubMed

Shapshay, S M; Rebeiz, E E; Bohigian, R K; Hybels, R L; Aretz, H T; Pankratov, M M

1991-02-01

Endoscopic sinus surgery has gained wide acceptance since its introduction into the United States. Complex sinus anatomy and troublesome bleeding have been associated with complications, which vary in severity from synechia to blindness and leakage of cerebrospinal fluid. Endoscopic sinus surgery using a holmium: yttrium aluminum garnet pulsed solid-state laser oscillating at 2.1 microns with fiberoptic delivery was performed in the laboratory, and the results were compared with those of conventional endoscopic sinus surgery. Three beagle dogs, six human cadaver heads, and one calf head were used in the in vivo and in vitro studies to evaluate the bone ablation, tissue coagulation, and hemostatic properties of the holmium: yttrium aluminum garnet laser. Modified endoscopic telescopes for sinus surgery, a newly developed handpiece for fiberoptic delivery, and other surgical instruments were used. The results indicate that the holmium: yttrium aluminum garnet laser and new delivery instrumentation provide good hemostasis and controlled soft-tissue ablation and bone removal. The access to all sinuses in the human cadaver model was very good. The canine in vivo study showed delayed but complete healing on the laser-treated side. Clinical evaluation of the holmium: yttrium aluminum garnet laser is warranted to increase the precision and safety of endoscopic sinus surgery.

Rabbit tissue model (RTM) harvesting technique.

PubMed

Medina, Marelyn

2002-01-01

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

The aerosol rabbit model of TB latency, reactivation and immune reconstitution inflammatory syndrome

PubMed Central

Manabe, Yukari C.; Kesavan, Anup K.; Lopez-Molina, Javier; Hatem, Christine L.; Brooks, Megan; Fujiwara, Ricardo; Hochstein, Karl; Pitt, M. Louise M.; Tufariello, JoAnn; Chan, John; McMurray, David N.; Bishai, William R.; Dannenberg, Arthur M.; Mendez, Susana

2015-01-01

The large reservoir of human latent tuberculosis (TB) contributes to the global success of the pathogen, Mycobacterium tuberculosis (Mtb). We sought to test whether aerosol infection of rabbits with Mtb H37Rv could model paucibacillary human latent TB. The lung burden of infection peaked at 5 weeks after aerosol infection followed by host containment of infection that was achieved in all rabbits. One-third of rabbits had at least one caseous granuloma with culturable bacilli at 36 weeks after infection suggesting persistent paucibacillary infection. Corticosteroid-induced immunosuppression initiated after disease containment resulted in reactivation of disease. Seventy-two percent of rabbits had culturable bacilli in the right upper lung lobe homogenates compared to none of the untreated controls. Discontinuation of dexamethasone led to predictable lymphoid recovery, with a proportion of rabbits developing multicentric large caseous granuloma. The development and severity of the immune reconstitution inflammatory syndrome (IRIS) was dependent on the antigen load at the time of immunosuppression and subsequent bacillary replication during corticosteroid-induced immunosuppression. Clinically, many aspects were similar to IRIS in severely immunosuppressed HIV-infected patients who have functional restoration of T cells in response to effective (highly active) antiretroviral therapy. This corticosteroid model is the only animal model of the IRIS. Further study of the rabbit model of TB latency, reactivation and IRIS may be important in understanding the immunopathogenesis of these poorly modeled states as well as for improved diagnostics for specific stages of disease. PMID:18068491

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

PubMed

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

2007-05-15

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

Sinus hypoplasia in the cystic fibrosis rat resolves in the absence of chronic infection.

PubMed

Grayson, Jessica; Tipirneni, Kiranya E; Skinner, Daniel F; Fort, Matthew; Cho, Do-Yeon; Zhang, Shaoyan; Prince, Andrew C; Lim, Dong-Jin; Mackey, Calvin; Woodworth, Bradford A

2017-09-01

Sinus hypoplasia is a hallmark characteristic in cystic fibrosis (CF). Chronic rhinosinusitis (CRS) is nearly universal from a young age, impaired sinus development could be secondary to loss of the cystic fibrosis transmembrane conductance regulator (CFTR) or consequences of chronic infection during maturation. The objective of this study was to assess sinus development relative to overall growth in a novel CF animal model. Sinus development was evaluated in CFTR -/- and CFTR +/+ rats at 3 stages of development: newborn; 3 weeks; and 16 weeks. Microcomputed tomography (microCT) scanning, cultures, and histology were performed. Three-dimensional sinus and skull volumes were quantified. At birth, sinus volumes were decreased in CFTR -/- rats compared with wild-type rats (mean ± SEM: 11.3 ± 0.85 mm 3 vs 14.5 ± 0.73 mm 3 ; p < 0.05), despite similar weights (8.4 ± 0.46 gm vs 8.3 ± 0.51 gm; p = 0.86). CF rat weights declined by 16 weeks (378.4 ± 10.6 gm vs 447.4 ± 15.9 gm; p < 0.05), sinus volume increased similar to wild-type rats (201.1 ± 3.77 gm vs 203.4 ± 7.13 gm; p = 0.8). The ratio of sinus volume to body weight indicates hypoplasia present at birth (1.37 ± 0.12 vs 1.78 ± 0.11; p < 0.05) and showed an increase compared with CFTR +/+ animals by 16 weeks (0.53 ± 0.02 vs 0.46 ± 0.02; p < 0.05). Rats did not develop histologic evidence of chronic infection. CF rat sinuses are smaller at birth, but develop volumes similar to wild-type rats with maturation. This suggests that loss of CFTR may confer sinus hypoplasia at birth, but normal development ensues without chronic sinus infection. © 2017 ARS-AAOA, LLC.

Modeling of the jack rabbit series of experiments with a temperature based reactive burn model

NASA Astrophysics Data System (ADS)

Desbiens, Nicolas

2017-01-01

The Jack Rabbit experiments, performed by Lawrence Livermore National Laboratory, focus on detonation wave corner turning and shock desensitization. Indeed, while important for safety or charge design, the behaviour of explosives in these regimes is poorly understood. In this paper, our temperature based reactive burn model is calibrated for LX-17 and compared to the Jack Rabbit data. It is shown that our model can reproduce the corner turning and shock desensitization behaviour of four out of the five experiments.

Mechanism underlying impaired cardiac pacemaking rhythm during ischemia: A simulation study

NASA Astrophysics Data System (ADS)

Bai, Xiangyun; Wang, Kuanquan; Yuan, Yongfeng; Li, Qince; Dobrzynski, Halina; Boyett, Mark R.; Hancox, Jules C.; Zhang, Henggui

2017-09-01

Ischemia in the heart impairs function of the cardiac pacemaker, the sinoatrial node (SAN). However, the ionic mechanisms underlying the ischemia-induced dysfunction of the SAN remain elusive. In order to investigate the ionic mechanisms by which ischemia causes SAN dysfunction, action potential models of rabbit SAN and atrial cells were modified to incorporate extant experimental data of ischemia-induced changes to membrane ion channels and intracellular ion homeostasis. The cell models were incorporated into an anatomically detailed 2D model of the intact SAN-atrium. Using the multi-scale models, the functional impact of ischemia-induced electrical alterations on cardiac pacemaking action potentials (APs) and their conduction was investigated. The effects of vagal tone activity on the regulation of cardiac pacemaker activity in control and ischemic conditions were also investigated. The simulation results showed that at the cellular level ischemia slowed the SAN pacemaking rate, which was mainly attributable to the altered Na+-Ca2+ exchange current and the ATP-sensitive potassium current. In the 2D SAN-atrium tissue model, ischemia slowed down both the pacemaking rate and the conduction velocity of APs into the surrounding atrial tissue. Simulated vagal nerve activity, including the actions of acetylcholine in the model, amplified the effects of ischemia, leading to possible SAN arrest and/or conduction exit block, which are major features of the sick sinus syndrome. In conclusion, this study provides novel insights into understanding the mechanisms by which ischemia alters SAN function, identifying specific conductances as contributors to bradycardia and conduction block.

Gefarnate stimulates mucin-like glycoprotein secretion in conjunctival tissue and ameliorates corneal epithelial damage in animal dry-eye models.

PubMed

Dota, Atsuyoshi; Takaoka-Shichijo, Yuko; Nakamura, Masatsugu

2013-01-01

The aim of this study was to evaluate the effect of gefarnate on mucin-like glycoprotein secretion in isolated rabbit conjunctival tissue, and on corneal epithelial damage in rabbit and cat dry-eye models. Conjunctival tissue isolated from rabbits was treated with gefarnate. Mucin-like glycoprotein was detected in the culture supernatant by an enzyme-linked lectin assay. Gefarnate ointment was topically applied to eyes once daily for 7 days in the rabbit dry-eye model, in which the lacrimal glands, Harderian gland, and nictitating membrane were removed, or for 4 weeks in the cat dry-eye model, in which the lacrimal gland and nictitating membrane were removed. Corneal epithelial damage was evaluated by measurement of corneal permeability by rose bengal in the rabbit model or by fluorescein staining in the cat model. Gefarnate stimulated mucin-like glycoprotein secretion in conjunctival tissue in a dose-dependent manner. In the rabbit dry-eye model, application of gefarnate ointment to the eyes resulted in a dose-dependent decrease in rose bengal permeability in the cornea, with the effect being significant at concentrations of ≥0.3%. In the cat dry-eye model, application of gefarnate ointment resulted in a significant decrease in the corneal fluorescein staining score. These results suggest that gefarnate stimulates in vitro secretion of mucin-like glycoprotein in conjunctival tissue and ameliorates corneal epithelial damage in animal dry-eye models. Gefarnate may therefore be effective for treating dry eye.

Vortex dynamics in Patient-Specific Stenotic Tricuspid and Bicuspid Aortic Valves pre- and post- Trans-catheter Aortic Valve Replacement

NASA Astrophysics Data System (ADS)

Hatoum, Hoda; Dasi, Lakshmi Prasad

2017-11-01

Understanding blood flow related adverse complications such as leaflet thrombosis post-transcatheter aortic valve implantation (TAVI) requires a deeper understanding of how patient-specific anatomic and hemodynamic factors, and relative valve positioning dictate sinus vortex flow and stasis regions. High resolution time-resolved particle image velocimetry measurements were conducted in compliant and transparent 3D printed patient-specific models of stenotic bicuspid and tricuspid aortic valve roots from patients who underwent TAVI. Using Lagrangian particle tracking analysis of sinus vortex flows and probability distributions of residence time and blood damage indices we show that (a) patient specific modeling provides a more realistic assessment of TAVI flows, (b) TAVI deployment alters sinus flow patterns by significantly decreasing sinus velocity and vorticity, and (c) relative valve positioning can control critical vortex structures that may explain preferential leaflet thrombosis corresponding to separated flow recirculation, secondary to valve jet vectoring relative to the aorta axis. This work provides new methods and understanding of the spatio-temporal aortic sinus vortex dynamics in post TAVI pathology. This study was supported by the Ohio State University DHLRI Trifit Challenge award.

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 mechanistic insight and should provide a solid “building-block” to generate more detailed ionic models to represent complex rabbit electrophysiology. PMID:27749895

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 insight and should provide a solid "building-block" to generate more detailed ionic models to represent complex rabbit electrophysiology.

Simulation of Cardiac Arrhythmias Using a 2D Heterogeneous Whole Heart Model

PubMed Central

Balakrishnan, Minimol; Chakravarthy, V. Srinivasa; Guhathakurta, Soma

2015-01-01

Simulation studies of cardiac arrhythmias at the whole heart level with electrocardiogram (ECG) gives an understanding of how the underlying cell and tissue level changes manifest as rhythm disturbances in the ECG. We present a 2D whole heart model (WHM2D) which can accommodate variations at the cellular level and can generate the ECG waveform. It is shown that, by varying cellular-level parameters like the gap junction conductance (GJC), excitability, action potential duration (APD) and frequency of oscillations of the auto-rhythmic cell in WHM2D a large variety of cardiac arrhythmias can be generated including sinus tachycardia, sinus bradycardia, sinus arrhythmia, sinus pause, junctional rhythm, Wolf Parkinson White syndrome and all types of AV conduction blocks. WHM2D includes key components of the electrical conduction system of the heart like the SA (Sino atrial) node cells, fast conducting intranodal pathways, slow conducting atriovenctricular (AV) node, bundle of His cells, Purkinje network, atrial, and ventricular myocardial cells. SA nodal cells, AV nodal cells, bundle of His cells, and Purkinje cells are represented by the Fitzhugh-Nagumo (FN) model which is a reduced model of the Hodgkin-Huxley neuron model. The atrial and ventricular myocardial cells are modeled by the Aliev-Panfilov (AP) two-variable model proposed for cardiac excitation. WHM2D can prove to be a valuable clinical tool for understanding cardiac arrhythmias. PMID:26733873

Hemodynamic effects of long-term morphological changes in the human carotid sinus.

PubMed

Seong, Jaehoon; Jeong, Woowon; Smith, Nataliya; Towner, Rheal A

2015-04-13

Previous investigations of morphology for human carotid artery bifurcation from infancy to young adulthood found substantial growth of the internal carotid artery with advancing age, and the development of the carotid sinus at the root of the internal carotid artery during teenage years. Although the reasons for the appearance of the carotid sinus are not clearly understood yet, it has been hypothesized that the dilation of the carotid sinus serves to support pressure sensing, and slows the blood flow to reduce pulsatility to protect the brain. In order to understand this interesting evolvement at the carotid bifurcation in the aspects of fluid mechanics, we performed in vitro phase-contrast MR flow experiments using compliant silicone replicas of age-dependent carotid artery bifurcations. The silicone models in childhood, adolescence, and adulthood were fabricated using a rapid prototyping technique, and incorporated with a bench-top flow mock circulation loop using a computer-controlled piston pump. The results of the in vitro flow study showed highly complex flow characteristics at the bifurcation in all age-dependent models. However, the highest magnitude of kinetic energy was found at the internal carotid artery in the child model. The high kinetic energy in the internal carotid artery during childhood might be one of the local hemodynamic forces that initiate morphological long-term development of the carotid sinus in the human carotid bifurcation. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

PubMed

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

2013-07-19

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

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

PubMed Central

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

2013-01-01

HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies (bNAb). We compared three different animal models: guinea pigs, rabbits and cynomolgus macaques. Envelope genes from the prototype isolate HIV-1 Bx08 and two elite neutralizers were included. Codon-optimized genes, encoded secreted gp140 or membrane bound gp150, were modified for expression of stabilized soluble trimer gene products, and delivered individually or mixed. Specific IgG after repeated i.d. inoculations with electroporation confirmed in vivo expression and immunogenicity. Evaluations of rabbits and guinea pigs displayed similar results. The superior DNA construct in rabbits was a trivalent mix of non-modified codon-optimized gp140 envelope genes. Despite NAb responses with some potency and breadth in guinea pigs and rabbits, the DNA vaccinated macaques displayed less bNAb activity. It was concluded that a trivalent mix of non-modified gp140 genes from rationally selected clinical isolates was, in this study, the best option to induce high and broad NAb in the rabbit model, but this optimization does not directly translate into similar responses in cynomolgus macaques. PMID:26344115

Rabbit as an animal model for intravitreal pharmacokinetics: Clinical predictability and quality of the published data.

PubMed

Del Amo, Eva M; Urtti, Arto

2015-08-01

Intravitreal administration is the method of choice in drug delivery to the retina and/or choroid. Rabbit is the most commonly used animal species in intravitreal pharmacokinetics, but it has been criticized as being a poor model of human eye. The critique is based on some anatomical differences, properties of the vitreous humor, and observed differences in drug concentrations in the anterior chamber after intravitreal injections. We have systematically analyzed all published information on intravitreal pharmacokinetics in the rabbit and human eye. The analysis revealed major problems in the design of the pharmacokinetic studies. In this review we provide advice for study design. Overall, the pharmacokinetic parameters (clearance, volume of distribution, half-life) in the human and rabbit eye have good correlation and comparable absolute values. Therefore, reliable rabbit-to-man translation of intravitreal pharmacokinetics should be feasible. The relevant anatomical and physiological parameters in rabbit and man show only small differences. Furthermore, the claimed discrepancy between drug concentrations in the human and rabbit aqueous humor is not supported by the data analysis. Based on the available and properly conducted pharmacokinetic studies, the differences in the vitreous structure in rabbits and human patients do not lead to significant pharmacokinetic differences. This review is the first step towards inter-species translation of intravitreal pharmacokinetics. More information is still needed to dissect the roles of drug delivery systems, disease states, age and ocular manipulation on the intravitreal pharmacokinetics in rabbit and man. Anyway, the published data and the derived pharmacokinetic parameters indicate that the rabbit is a useful animal model in intravitreal pharmacokinetics. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Histologic Evaluation of Micronized AlloDerm After Injection Laryngoplasty in a Rabbit Model.

PubMed

Oldenburg, Michael S; Janus, Jeff; Voss, Steve; San Marina, Serban; Chen, Tiffany; Garcia, Joaquin; Ekbom, Dale

2017-05-01

Micronized AlloDerm is a commonly used injectable material for injection laryngoplasty; however, the histologic response to laryngeal implantation and resorption rate over time have not been elucidated. This study aimed to evaluate the in vivo response of micronized AlloDerm over time after laryngeal implantation using a rabbit model. Animal model. The left recurrent laryngeal nerve was sectioned in five New Zealand White rabbits to create a vocal cord paralysis. Two weeks later, injection laryngoplasty was performed with 100 μL of micronized AlloDerm. Animals were sacrificed 4 (two rabbits) and 12 (three rabbits) weeks after injection. Histologic sections were stained and evaluated by a single pathologist. Volume estimates were made by assuming the implant took an ellipsoid shape using dimensions calculated from histologic slides. In all cases, histological analysis revealed a lymphocytic inflammatory response infiltrating the peripheral margins of injection. After 4 weeks, the volume of injected material remaining in two rabbits was 404 and 278 mm 3 (average 341 mm 3 ). After 12 weeks, the volume of injected material remaining in three rabbits was 0, 61, and 124 mm 3 (average 62 mm 3 ), an 82% difference in volume of material between animals sacrificed at 4 weeks versus 12 weeks. Injection laryngoplasty using micronized AlloDerm induces a lymphocytic inflammatory response after injection in a rabbit model. Though a significant amount of material remains after 4 weeks, by 12 weeks the majority has been reabsorbed. NA Laryngoscope, 127:E166-E169, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

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

PubMed

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

2015-05-01

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

Model Validation Against The Modelers’ Data Archive

DTIC Science & Technology

2014-08-01

completion of the planned Jack Rabbit 2 field trials. The relevant task for the effort addressed here is Task 4 of the current Interagency Agreement, as...readily simulates the Prairie Grass sulfur dioxide plumes. Also, Jack Rabbit II field trials are set to be completed during FY16. Once these data are...available, they will also be used to validate the combined models. This validation may prove to be more useful, as the Jack Rabbit II will release

Biocompatibility of poly(ethylene glycol) and poly(acrylic acid) interpenetrating network hydrogel by intrastromal implantation in rabbit cornea

PubMed Central

Zheng, Luo Luo; Vanchinathan, Vijay; Dalal, Roopa; Noolandi, Jaan; Waters, Dale J.; Hartmann, Laura; Cochran, Jennifer R.; Frank, Curtis W.; Yu, Charles Q.; Ta, Christopher N.

2015-01-01

We evaluated the biocompatibility of a poly(ethylene glycol) and poly(acrylic acid) (PEG/PAA) interpenetrating network hydrogel designed for artificial cornea in a rabbit model. PEG/PAA hydrogel measuring 6 mm in diameter was implanted in the corneal stroma of twelve rabbits. Stromal flaps were created with a microkeratome. Randomly, six rabbits were assigned to bear the implant for 2 months, two rabbits for 6 months, two rabbits for 9 months, one rabbit for 12 months, and one rabbit for 16 months. Rabbits were evaluated monthly. After the assigned period, eyes were enucleated, and corneas were processed for histology and immunohistochemistry. There were clear corneas in three of six rabbits that had implantation of hydrogel for 2 months. In the six rabbits with implant for 6 months or longer, the corneas remained clear in four. There was a high rate of epithelial defect and corneal thinning in these six rabbits. One planned 9-month rabbit developed extrusion of implant at 4 months. The cornea remained clear in the 16-month rabbit but histology revealed epithelial in-growth. Intrastromal implantation of PEG/PAA resulted in a high rate of long-term complications. PMID:25778285

Automated Cross-Sectional Measurement Method of Intracranial Dural Venous Sinuses.

PubMed

Lublinsky, S; Friedman, A; Kesler, A; Zur, D; Anconina, R; Shelef, I

2016-03-01

MRV is an important blood vessel imaging and diagnostic tool for the evaluation of stenosis, occlusions, or aneurysms. However, an accurate image-processing tool for vessel comparison is unavailable. The purpose of this study was to develop and test an automated technique for vessel cross-sectional analysis. An algorithm for vessel cross-sectional analysis was developed that included 7 main steps: 1) image registration, 2) masking, 3) segmentation, 4) skeletonization, 5) cross-sectional planes, 6) clustering, and 7) cross-sectional analysis. Phantom models were used to validate the technique. The method was also tested on a control subject and a patient with idiopathic intracranial hypertension (4 large sinuses tested: right and left transverse sinuses, superior sagittal sinus, and straight sinus). The cross-sectional area and shape measurements were evaluated before and after lumbar puncture in patients with idiopathic intracranial hypertension. The vessel-analysis algorithm had a high degree of stability with <3% of cross-sections manually corrected. All investigated principal cranial blood sinuses had a significant cross-sectional area increase after lumbar puncture (P ≤ .05). The average triangularity of the transverse sinuses was increased, and the mean circularity of the sinuses was decreased by 6% ± 12% after lumbar puncture. Comparison of phantom and real data showed that all computed errors were <1 voxel unit, which confirmed that the method provided a very accurate solution. In this article, we present a novel automated imaging method for cross-sectional vessels analysis. The method can provide an efficient quantitative detection of abnormalities in the dural sinuses. © 2016 by American Journal of Neuroradiology.

Gefarnate stimulates mucin-like glycoprotein secretion in conjunctival tissue and ameliorates corneal epithelial damage in animal dry-eye models

PubMed Central

Dota, Atsuyoshi; Takaoka-Shichijo, Yuko; Nakamura, Masatsugu

2013-01-01

Purpose The aim of this study was to evaluate the effect of gefarnate on mucin-like glycoprotein secretion in isolated rabbit conjunctival tissue, and on corneal epithelial damage in rabbit and cat dry-eye models. Methods Conjunctival tissue isolated from rabbits was treated with gefarnate. Mucin-like glycoprotein was detected in the culture supernatant by an enzyme-linked lectin assay. Gefarnate ointment was topically applied to eyes once daily for 7 days in the rabbit dry-eye model, in which the lacrimal glands, Harderian gland, and nictitating membrane were removed, or for 4 weeks in the cat dry-eye model, in which the lacrimal gland and nictitating membrane were removed. Corneal epithelial damage was evaluated by measurement of corneal permeability by rose bengal in the rabbit model or by fluorescein staining in the cat model. Results Gefarnate stimulated mucin-like glycoprotein secretion in conjunctival tissue in a dose-dependent manner. In the rabbit dry-eye model, application of gefarnate ointment to the eyes resulted in a dose-dependent decrease in rose bengal permeability in the cornea, with the effect being significant at concentrations of ≥0.3%. In the cat dry-eye model, application of gefarnate ointment resulted in a significant decrease in the corneal fluorescein staining score. Conclusion These results suggest that gefarnate stimulates in vitro secretion of mucin-like glycoprotein in conjunctival tissue and ameliorates corneal epithelial damage in animal dry-eye models. Gefarnate may therefore be effective for treating dry eye. PMID:23386781

Rabbits with naturally occurring cataracts referred for phacoemulsification and intraocular lens implantation: a preliminary study of 12 cases.

PubMed

Sanchez, Rick F; Everson, Richard; Hedley, Joanna; Dawson, Charlotte; Lam, Richard; Priestnall, Simon L; Garcia de Carellan, Alejandra; de Miguel, Cristina; Seymour, Christopher

2017-12-04

To describe the presentation of 15 rabbits with naturally occurring cataracts referred for phacoemulsification surgery, the procedure in 13 cases and the follow-up in 12. Fifteen rabbits (30 eyes), nine of which stopped following visual cues in association with cataract progression. Rabbits underwent preoperative ophthalmic and ocular ultrasound examination. Thirteen rabbits (22 eyes) had mature cataracts. Ten were bilateral and three unilateral. Two rabbits had an anterior chamber abscess. The cataract in one of these was incipient. One rabbit had bilateral immature cataracts. One rabbit had a subluxated lens, and one had a retinal detachment. Thirteen rabbits (22 eyes) underwent phacoemulsification. Eighteen, 13.5-mm capsular tension rings (CTRs) and seventeen, 13-mm IOLs (Acrivet ® , Berlin, Germany) were fitted including one 41D 60V-model, and three 49D and thirteen 58D 20S-models. Intraoperative complications included one unilateral posterior-capsular tear, one lens subluxation, and one expulsive choroidal hemorrhage. One rabbit died during anesthetic recovery. Nine cases were PCR-tested for Encephalitozoon cuniculi, and only three were positive. The median follow-up time was 12 months (4-24 months). Rabbits that were not following visual cues preoperatively did so postoperatively, and surgery resulted in a clear visual axis for the follow-up period in every case except in two, due to reasons other than the surgery. Phacoemulsification with CTR and IOL implantation offers good long-term results and can improve the quality of life of pet rabbits. Retinal detachment, lens luxation, expulsive choroidal hemorrhage, and anesthetic death are potential complications. © 2017 American College of Veterinary Ophthalmologists.

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

PubMed

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

2001-04-01

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

Therapeutic trials for a rabbit model of EBV-associated Hemophagocytic Syndrome (HPS): effects of vidarabine or CHOP, and development of Herpesvirus papio (HVP)-negative lymphomas surrounded by HVP-infected lymphoproliferative disease.

PubMed

Hayashi, K; Joko, H; Koirala, T R; Onoda, S; Jin, Z-S; Munemasa, M; Ohara, N; Oda, W; Tanaka, T; Oka, T; Kondo, E; Yoshino, T; Takahashi, K; Yamada, M; Akagi, T

2003-10-01

Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS), which is often associated with fatal infectious mononucleosis or T-cell lymphoproliferative diseases (LPD), is a distinct disease characterized by high mortality. Treatment of patients with EBV-AHS has proved challenging. To develop some therapeutic interventions for EBV-AHS, we examined the effectiveness of an antiviral agent (vidarabine) or chemotherapy (CHOP), using a rabbit model for EBV-AHS. Fourteen untreated rabbits were inoculated intravenously with cell-free virions of the EBV-like virus Herpesvirus papio (HVP). All of the rabbits died of HVP-associated (LPD) and hemophagocytic syndrome (HPS) between 21 and 31 days after inoculation. Furthermore, three HVP-infected rabbits treated with vidarabine died between days 23 and 28 after inoculation, and their clinicopathological features were no different from those of untreated rabbits, indicating that this drug is not effective at all to treat HVP-induced rabbit LPD and HPS. Three of the infected rabbits that were treated with one course, with an incomplete set of three courses, or with three full courses of CHOP treatment died of HVP-induced LPD and HPS with a bleeding tendency and/or with opportunistic infections. They died on the 26th, 62nd and 105th day after virus inoculation, respectively. CHOP treatment transiently suppressed the HVP-induced LPD and contributed to the prolonged survival time of two infected rabbits. However, it did not remove all of the HVP-infected cells from the infected rabbits, and residual HVP-infected lymphocytes caused recurrences of rabbit LPD and HPS. The most interesting finding of this experiment was observed in the infected rabbit with the longest survival time of 105 days: HVP-negative lymphomas surrounded by HVP-induced LPD developed in the larynx and ileum of this rabbit, causing an obstruction of the lumen. We concluded that these were not secondary lymphomas caused by CHOP treatment, because no suspicious lesions were detected in three uninfected rabbits that were treated with three courses of CHOP for 120 days. It is therefore necessary to clarify the mechanism by which HVP-negative lymphomas associated with HVP-induced LPD can develop. Our data from therapeutic trials using EBV-AHS animal models indicate that vidarabine is not effective as an agent to treat HVP-infected rabbits, and even the cytotoxic chemotherapy of CHOP is not sufficient to cure the HVP-infected rabbits or to prolong the survival time of infected rabbits. Further studies will therefore be required to develop better therapies to treat EBV-AHS.

Rabbitpox virus and vaccinia virus infection of rabbits as a model for human smallpox.

PubMed

Adams, Mathew M; Rice, Amanda D; Moyer, R W

2007-10-01

The threat of smallpox release and use as a bioweapon has encouraged the search for new vaccines and antiviral drugs, as well as development of new small-animal models in which their efficacy can be determined. Here, we reinvestigate a rabbit model in which the intradermal infection of rabbits with very low doses of either rabbitpox virus (RPV) or vaccinia virus Western Reserve (VV-WR) recapitulates many of the clinical features of human smallpox. Following intradermal inoculation with RPV, rabbits develop systemic disease characterized by extensive viremia, numerous secondary lesions on the skin and mucocutaneous tissues, severe respiratory disease, death by 9 days postinfection, and, importantly, natural aerosol transmission between animals. Contrary to previous reports, intradermal infection with VV-WR also resulted in a very similar lethal systemic disease in rabbits, again with natural aerosol transmission between animals. When sentinel and index animals were cohoused, transmission rates approached 100% with either virus, with sentinel animals exhibiting a similar, severe disease. Lower rates of transmission were observed when index and sentinel animals were housed in separate cages. Sentinel animals infected with RPV with one exception succumbed to the disease. However, the majority of VV-WR-infected sentinel animals, while becoming seriously ill, survived. Finally, we tested the efficacy of the drug 1-O-hexadecyloxypropyl-cidofovir in the RPV/rabbit model and found that an oral dose of 5 mg/kg twice a day for 5 days beginning 1 day before infection was able to completely protect rabbits from lethal disease.

Healthy rabbits are susceptible to Epstein-Barr virus infection and infected cells proliferate in immunosuppressed animals.

PubMed

Khan, Gulfaraz; Ahmed, Waqar; Philip, Pretty S; Ali, Mahmoud H; Adem, Abdu

2015-02-18

Epstein-Barr virus (EBV) is an oncogenic virus implicated in the pathogenesis of several human malignancies. However, due to the lack of a suitable animal model, a number of fundamental questions pertaining to the biology of EBV remain poorly understood. Here, we explore the potential of rabbits as a model for EBV infection and investigate the impact of immunosuppression on viral proliferation and gene expression. Six healthy New Zealand white rabbits were inoculated intravenously with EBV and blood samples collected prior to infection and for 7 weeks post-infection. Three weeks after the last blood collection, animals were immunosuppressed with daily intramuscular injections of cyclosporin A at doses of 20 mg/kg for 15 days and blood collected twice a week from each rabbit. The animals were subsequently sacrificed and tissues from all major organs were collected for subsequent analysis. Following intravenous inoculation, all 6 rabbits seroconverted with raised IgG and IgM titres to EBV, but viral DNA in peripheral blood mononuclear cells (PBMCs) could only be detected intermittently. Following immunosuppression however, EBV DNA could be readily detected in PBMCs from all 4 rabbits that survived the treatment. Quantitative PCR indicated an increase in EBV viral load in PBMCs as the duration of immunosuppression increased. At autopsy, splenomegaly was seen in 3/4 rabbits, but spleens from all 4 rabbit were EBV PCR positive. EBER-in situ hybridization and immunoshistochemistry revealed the presence of a large number of EBER-positive and LMP-1 positive lymphoblasts in the spleens of 3/4 rabbits. To a lesser extent, EBER-positive cells were also seen in the portal tract regions of the liver of these rabbits. Western blotting indicated that EBNA-1 and EBNA-2 were also expressed in the liver and spleen of infected animals. EBV can infect healthy rabbits and the infected cells proliferate when the animals are immunocompromised. The infected cells expressed several EBV-latent gene products which are probably driving the proliferation, reminiscent of what is seen in immunocompromised individuals. Further work is required to explore the potential of rabbits as an animal model for studying EBV biology and tumorigenesis.

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

PubMed

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

2013-07-01

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

Infrastructure features outperform environmental variables explaining rabbit abundance around motorways.

PubMed

Planillo, Aimara; Malo, Juan E

2018-01-01

Human disturbance is widespread across landscapes in the form of roads that alter wildlife populations. Knowing which road features are responsible for the species response and their relevance in comparison with environmental variables will provide useful information for effective conservation measures. We sampled relative abundance of European rabbits, a very widespread species, in motorway verges at regional scale, in an area with large variability in environmental and infrastructure conditions. Environmental variables included vegetation structure, plant productivity, distance to water sources, and altitude. Infrastructure characteristics were the type of vegetation in verges, verge width, traffic volume, and the presence of embankments. We performed a variance partitioning analysis to determine the relative importance of two sets of variables on rabbit abundance. Additionally, we identified the most important variables and their effects model averaging after model selection by AICc on hypothesis-based models. As a group, infrastructure features explained four times more variability in rabbit abundance than environmental variables, being the effects of the former critical in motorway stretches located in altered landscapes with no available habitat for rabbits, such as agricultural fields. Model selection and Akaike weights showed that verge width and traffic volume are the most important variables explaining rabbit abundance index, with positive and negative effects, respectively. In the light of these results, the response of species to the infrastructure can be modulated through the modification of motorway features, being some of them manageable in the design phase. The identification of such features leads to suggestions for improvement through low-cost corrective measures and conservation plans. As a general indication, keeping motorway verges less than 10 m wide will prevent high densities of rabbits and avoid the unwanted effects that rabbit populations can generate in some areas.

Mechanism of feedback regulation of neutrophil inflammation in Henoch-Schönlein purpura.

PubMed

Wu, J-J; Zhu, Y-T; Hu, Y-M

2016-10-01

The aim of this study is to investigate the role of complement-neutrophil feedback regulation of inflammatory response in Henoch-Schönlein purpura (HSP) through constructing an animal model of HSP. Twenty-four SPF grade Japanese large-eared white rabbits were randomly divided into normal group and model group, 12 for each group. HSP model was constructed by challenging rabbits with gastric gavage of a decoction solution containing ginger, Piper longum L. and pepper, intraperitoneal injection of ovalbumin (OVA)-Freund's adjuvant and intravenous injection at marginal ear vein and subcutaneous injection in the back of rabbits with OVA normal saline solution. Changes in general conditions of rabbits including food intake, water intake and body temperature as well as alterations in blood routine, urine routine, reactive oxygen species (ROS), inflammatory cytokines and complement were compared between two groups. In the meantime, N-Acetyl-L-Cysteine (NAC)and hydrogen peroxide (H2O2) treatment was used to manipulate ROS level and determined the changes in aforementioned parameters. After sensitization, rabbits of the model group displayed significantly elevated body temperature, apathy, reduced physical activity, significantly decreased water and food intake compared to the situations before sensitization (p<0.05). Significant pathological changes were observed in these rabbits through HE staining study. Furthermore, blood levels of white blood cells (WBC), mean corpuscular hemoglobin concentration (MCHC), neutrophils (NEU) and NEU% were significantly increased, whereas levels of red blood cells (RBC), hemoglobin (HGB), eosinophils (EOS) and EOS% were significantly decreased (p<0.05). No significant alterations were observed in levels of mean corpuscular hemoglobin (MCH) and platelet (PLT) (p>0.05). Urine with mucus and a strong odor was observed in model rabbits. Proteinuria occurred in 66.67% of model rabbits, hematuria in 58.33% and presence of WBC in the urine in 25%. Also, levels of ROS, inflammatory cytokines, tumor growth factor (TGF)-β, complement and tumor necrosis factor (TNF)-α were significantly increased in model rabbits. After the treatment of ROS inhibitor, NAC, levels of these parameters were significantly decreased (p<0.05), but significantly increased after treatment of H2O2, the ROS agonist (p<0.05). Complement-neutrophil feedback regulation of inflammatory response plays important roles in the pathogenesis of HSP, and inhibition of ROS can suppress the development and progression of HSP.

Brief Report: Social Skills, Internalizing and Externalizing Symptoms, and Respiratory Sinus Arrhythmia in Autism

ERIC Educational Resources Information Center

Neuhaus, Emily; Bernier, Raphael; Beauchaine, Theodore P.

2014-01-01

Theoretical and empirical models describe respiratory sinus arrhythmia (RSA) as a peripheral biomarker of emotion regulation and social competence. Recent findings also link RSA to individual differences in social functioning within autism spectrum disorder (ASD). However, associations between RSA and symptoms of internalizing/externalizing…

[Study on effect of cordyceps sinensis on early-stage silicotic pulmonary fibrosis in rabbits].

PubMed

Liu, Qianzhong; Zhang, Wei; Cui, Hongfu; Ying, Yanhong

2014-07-01

To establish a rabbit model of silicotic pulmonary fibrosis and to investigate the effect of cordyceps sinensis in this model. Thirty healthy male white rabbits were randomly divided into control group, silicosis model group, and intervention group. The rabbits in silicosis model group and intervention group received endotracheal perfusion of silicon dioxide suspension (120 mg/kg), and the control group was treated with the same volume of saline. All the rabbits were sacrificed 30 days later. The lung coefficient was calculated by comparing the lung weight and body weight; the right lung tissue was stained with hematoxylin-eosin (HE). The content of hydroxyproline in lung tissue was measured by alkaline hydrolysis. The mRNA levels of transforming growth factor beta 1 (TGF-β₁) and mothers against decapentaplegic homolog 7 (Smad7) in rabbit lung sections were determined by real-time PCR. No abnormalities were observed by HE staining in the lung tissues of control group, while fibrosis and silicotic nodules were discovered in the silicosis model group and intervention group. The lung coefficient and the content of hydroxyproline in lung tissue were significantly higher in the silicosis model group than in the control group and intervention group (P < 0.05 or P < 0.01). Compared with the control group, the silicosis model group and intervention group had significantly increased TGF-β₁ mRNA levels but significantly reduced Smad7 mRNA levels (P < 0.02). Compared with the silicosis model group, the intervention group had a significantly reduced TGF-β₁ mRNA level but a significantly increased Smad7 mRNA level (P < 0.05). Cordyceps sinensis is able to reduce the expression of TGF-β₁ mRNA and increase the expression of Smad7 mRNA in lung tissues of rabbits with silicotic pulmonary fibrosis, and thus postpone the progression of fibrosis.

CRISPR/Cas9-mediated mutation of PHEX in rabbit recapitulates human X-linked hypophosphatemia (XLH).

PubMed

Sui, Tingting; Yuan, Lin; Liu, Huan; Chen, Mao; Deng, Jichao; Wang, Yong; Li, Zhanjun; Lai, Liangxue

2016-07-01

X-linked hypophosphatemia (XLH) is the most common cause of inheritable rickets, with an incidence of 1/20 000 in humans. Inactivation or mutation of the gene PHEX, a phosphate-regulating endopeptidase, leads to hypophosphatemia and defective bone mineralization in XLH patients. Presently, there is no adequate animal model for safety assessments of physiotherapies and drug screening for XLH rickets. In this study, an XLH model was generated via PHEX gene knockout (KO) through coinjection of clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 (Cas9)/sgRNA mRNA into rabbit zygotes. The typical phenotypes of growth retardation, hypophosphatemia, elevated serum FGF23 and bone mineralization were observed in the PHEX KO rabbits but not in normal controls. In summary, for the first time, we have successfully obtained PHEX KO rabbits and recapitulated human XLH using the CRISPR/Cas9 system. This novel XLH rabbit model could be utilized as a drug screening model for XLH prevention and preclinical therapy. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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.

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

PubMed

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

2010-07-01

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

Truncated C-terminus of fibrillin-1 induces Marfanoid-progeroid-lipodystrophy (MPL) syndrome in rabbit.

PubMed

Chen, Mao; Yao, Bing; Yang, Qiangbing; Deng, Jichao; Song, Yuning; Sui, Tingting; Zhou, Lina; Yao, HaoBing; Xu, Yuanyuan; Ouyang, Hongsheng; Pang, Daxin; Li, Zhanjun; Lai, Liangxue

2018-04-09

Various clinical differences have been observed between patients with the FBN1 gene mutation and those with the classical Marfan phenotype. Although FBN1 knockout (KO) or dominant-negative mutant mice are widely used as an animal model for Marfan syndrome (MFS), these mice cannot recapitulate the genotype/phenotype relationship of Marfanoid-progeroid-lipodystrophy (MPL) syndrome, which is caused by a mutation in the C-terminus of fibrillin-1, the penultimate exon of the FBN1 gene. Here, we describe the generation of a rabbit MPL model with C-terminal truncation of fibrillin-1 using a CRISPR/Cas9 system. FBN1 heterozygous ( FBN1 Het) rabbits faithfully recapitulated the phenotypes of MFS, including muscle wasting and impaired connective tissue, ocular syndrome and aortic dilation. Moreover, skin symptoms, lipodystrophy, growth retardation and dysglycemia were also seen in these FBN1 Het rabbits, and have not been reported in other animal models. In conclusion, this novel rabbit model mimics the histopathological changes and functional defects of MPL syndrome, and could become a valuable model for studies of pathogenesis and drug screening for MPL syndrome. © 2018. Published by The Company of Biologists Ltd.

Early anticoagulation therapy for severe burns complicated by inhalation injury in a rabbit model

PubMed Central

Fu, Zhong-Hua; Guo, Guang-Hua; Xiong, Zhen-Fang; Liao, Xincheng; Liu, Ming-Zhuo; Luo, Jinhua

2017-01-01

The aim of the present study was to determine the effects of early anticoagulation treatment on severe burns complicated by inhalation injury in a rabbit model. Under anesthetization, an electrical burns instrument (100°C) was used to scald the backs of rabbits for 15 sec, which established a 30% III severe burns model. Treatment of the rabbits with early anticoagulation effectively improved the severe burns complicated by inhalation injury-induced lung injury, reduced PaO2, PaCO2 and SPO2 levels, suppressed the expression of tumor necrosis factor-α, interleukin (IL)-1β and IL-6, and increased the activity of IL-10. In addition, it was found that early anticoagulation treatment effectively suppressed the activities of caspase-3 and caspase-9, upregulated the protein expression of vascular endothelial growth factor (VEGF) and decreased the protein expression of protease-activated receptor 1 (PAR1) in the severe burns model. It was concluded that early anticoagulation treatment affected the severe burns complicated by inhalation injury in a rabbit model through the upregulation of VEGF and downregulation of PAR1 signaling pathways. Thus, early anticoagulation is a potential therapeutic option for severe burns complicated by inhalation injury. PMID:28944866

[The rule of lymphatic formation in rabbit VX2 supraglottic carcinoma model with lymph node metastasis].

PubMed

Zhang, Pin; Ji, Wenyue; Zhang, Xiangbo

2012-02-01

Establishment of transplanted model of VX2 supraglottic carcinoma in rabbits and investigation the rule of lymphatic vessels formation. After establishment of VX2 tumor-bearing rabbits, the carcinoma tissues were transplanted into the operculum laryngis submucosa in sixty New-Zealand white rabbits to establish transplanted tumor model. Vascular endothelial growth factor-3 (VEGFR-3) label staining was performed to observe lymphatic vessels. Number density, volume density of lymphatics periphery region of carcinoma, normal region and centre region were measured using computer image analysis system. There was no lymphatic vessels in carcinomatous centre region,but the lymphatic vessels number density, volume density in periphery region was much more than normal region. Their cavities were dilated. The discrepancy had statistical significance (P<0.01). The rule of lymphatic formation in rabbit VX2 supraglottic carcinoma model mimesis rule of lymphatic formation anthropo- supraglottic carcinoma. Lymphatic multiplication and dilation at periphery region of carcinoma is associated with lymph node metastasis. Evaluation of it at periphery region of carcinoma may be useful in predicting lymph node metastasis in patients with supraglottic carcinoma. This conclusion provides theoretical basis for utility of the anti-tumor medicines which inhibit lymphatic formation in animal model.

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.

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

NASA Astrophysics Data System (ADS)

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

2016-03-01

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

Wavelet-based system identification of short-term dynamic characteristics of arterial baroreflex.

PubMed

Kashihara, Koji; Kawada, Toru; Sugimachi, Masaru; Sunagawa, Kenji

2009-01-01

The assessment of arterial baroreflex function in cardiovascular diseases requires quantitative evaluation of dynamic and static baroreflex properties because of the frequent modulation of baroreflex properties with unstable hemodynamics. The purpose of this study was to identify the dynamic baroreflex properties from transient changes of step pressure inputs with background noise during a short-duration baroreflex test in anesthetized rabbits with isolated carotid sinuses, using a modified wavelet-based time-frequency analysis. The proposed analysis was able to identify the transfer function of baroreflex as well as static properties from the transient input-output responses under normal [gain at 0.04 Hz from carotid sinus pressure (CSP) to arterial pressure (n = 8); 0.29 +/- 0.05 at low (40-60 mmHg), 1.28 +/- 0.12 at middle (80-100 mmHg), and 0.38 +/- 0.07 at high (120-140 mmHg) CSP changes] and pathophysiological [gain in control vs. phenylbiguanide (n = 8); 0.32 +/- 0.07 vs. 0.39 +/- 0.09 at low, 1.39 +/- 0.15 vs. 0.59 +/- 0.09 (p < 0.01) at middle, and 0.35 +/- 0.04 vs. 0.15 +/- 0.02 (p < 0.01) at high CSP changes] conditions. Subsequently, we tested the proposed wavelet-based method under closed-loop baroreflex responses; the simulation study indicates that it may be applicable to clinical situations for accurate assessment of dynamic baroreflex function. In conclusion, the dynamic baroreflex property to various pressure inputs could be simultaneously extracted from the step responses with background noise.

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

[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.

Toward smart Nebulization: Engineering acoustic airflow to penetrate maxillary sinuses in chronic rhinosinusitis.

PubMed

Moghadam, Shima Jowhari; Navarro, Laurent; Leclerc, Lara; Hodin, Sophie; Pourchez, Jérémie

2018-07-30

Treating chronic rhinosinusitis (CRS) by nebulization requires an airflow capable to deliver medication to deep target sites beyond the nasal valve. Fixed frequency acoustic airflow technology is currently available, mainly as post-surgical therapy, but still have not been able to realize the full potential of direct nose to paranasal sinuses delivery. Reported herein are the application of frequency sweep acoustic airflow and the optimization of its frequency range, sweep cycle duration and intensity. The resonant frequencies of the model's maxillary sinuses can be estimated using the Helmholtz resonator theory. Results indicated a resonant frequency of 479 Hz for the right maxillary sinus and one of 849 Hz for the left maxillary sinus. The highest intrasinus deposition within the experiments are from sweep cycle duration of 1 s, intensity of 80 dB, and frequency range of 100-850 Hz. The optimal range of frequency determined from experiments is in good agreement with the corresponding frequency range obtained from the Helmholtz resonator theory. Results reveal a significantly enhanced maxillary sinus drug deposition. This technique affords the potential of treating CRS. Copyright © 2018 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2016-01-01

Tularemia is a severe, zoonotic disease caused by a gram-negative bacterium, Francisella tularensis. We have previously shown that rabbits are a good model of human pneumonic tularemia when exposed to aerosols containing a virulent, type A strain, SCHU S4. We further demonstrated that the live vaccine strain (LVS), an attenuated type B strain, extended time to death when given by scarification. Oral or aerosol vaccination has been previously shown in humans to offer superior protection to parenteral vaccination against respiratory tularemia challenge. Both oral and aerosol vaccination with LVS were well tolerated in the rabbit with only minimal fever and no weight loss after inoculation. Plasma antibody titers against F. tularensis were higher in rabbits that were vaccinated by either oral or aerosol routes compared to scarification. Thirty days after vaccination, all rabbits were challenged with aerosolized SCHU S4. LVS given by scarification extended time to death compared to mock-vaccinated controls. One orally vaccinated rabbit did survive aerosol challenge, however, only aerosol vaccination extended time to death significantly compared to scarification. These results further demonstrate the utility of the rabbit model of pneumonic tularemia in replicating what has been reported in humans and macaques as well as demonstrating the utility of vaccination by oral and respiratory routes against an aerosol tularemia challenge. PMID:27511964

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 electrophysiology and validation of cardiac AP models. Copyright © 2011 Elsevier Ltd. All rights reserved.

Deterministic Models of Inhalational Anthrax in New Zealand White Rabbits

PubMed Central

2014-01-01

Computational models describing bacterial kinetics were developed for inhalational anthrax in New Zealand white (NZW) rabbits following inhalation of Ames strain B. anthracis. The data used to parameterize the models included bacterial numbers in the airways, lung tissue, draining lymph nodes, and blood. Initial bacterial numbers were deposited spore dose. The first model was a single exponential ordinary differential equation (ODE) with 3 rate parameters that described mucociliated (physical) clearance, immune clearance (bacterial killing), and bacterial growth. At 36 hours postexposure, the ODE model predicted 1.7×107 bacteria in the rabbit, which agreed well with data from actual experiments (4.0×107 bacteria at 36 hours). Next, building on the single ODE model, a physiological-based biokinetic (PBBK) compartmentalized model was developed in which 1 physiological compartment was the lumen of the airways and the other was the rabbit body (lung tissue, lymph nodes, blood). The 2 compartments were connected with a parameter describing transport of bacteria from the airways into the body. The PBBK model predicted 4.9×107 bacteria in the body at 36 hours, and by 45 hours the model showed all clearance mechanisms were saturated, suggesting the rabbit would quickly succumb to the infection. As with the ODE model, the PBBK model results agreed well with laboratory observations. These data are discussed along with the need for and potential application of the models in risk assessment, drug development, and as a general aid to the experimentalist studying inhalational anthrax. PMID:24527843

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

PubMed

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

1998-03-01

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

Derivation of Rabbit Embryonic Stem Cells from Vitrified–Thawed Embryos

PubMed Central

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

2015-01-01

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

Computational Fluid Dynamics Modeling of Bacillus anthracis ...

EPA Pesticide Factsheets

Journal Article Three-dimensional computational fluid dynamics and Lagrangian particle deposition models were developed to compare the deposition of aerosolized Bacillus anthracis spores in the respiratory airways of a human with that of the rabbit, a species commonly used in the study of anthrax disease. The respiratory airway geometries for each species were derived from computed tomography (CT) or µCT images. Both models encompassed airways that extended from the external nose to the lung with a total of 272 outlets in the human model and 2878 outlets in the rabbit model. All simulations of spore deposition were conducted under transient, inhalation-exhalation breathing conditions using average species-specific minute volumes. Four 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. Despite the complex airway geometries in the rabbit nose, higher spore deposition efficiency was predicted in the upper conducting airways of the human at the same air concentration of anthrax spores. This greater deposition of spores in the upper airways in the human resulted in lower penetration and deposition in the tracheobronchial airways and the deep lung than that predict

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

PubMed Central

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

1998-01-01

The main limitation of both the rabbit and mouse models of rotavirus infection is that human rotavirus (HRV) strains do not replicate efficiently in either animal. The identification of individual genes necessary for conferring replication competence in a heterologous host is important to an understanding of the host range restriction of rotavirus infections. We recently reported the identification of the P type of the spike protein VP4 of four lapine rotavirus strains as being P[14]. To determine whether VP4 is involved in host range restriction in rabbits, we evaluated infection in rotavirus antibody-free rabbits inoculated orally with two P[14] HRVs, PA169 (G6) and HAL1166 (G8), and with several other HRV strains and animal rotavirus strains of different P and G types. We also evaluated whether the parental rhesus rotavirus (RRV) (P5B[3], G3) and the derived RRV-HRV reassortant candidate vaccine strains RRV × D (G1), RRV × DS-1 (G2), and RRV × ST3 (G4) would productively infect rabbits. Based on virus shedding, limited replication was observed with the P[14] HRV strains and with the SA11 Cl3 (P[2], G3) and SA11 4F (P6[1], G3) animal rotavirus strains, compared to the homologous ALA strain (P[14], G3). However, even limited infection provided complete protection from rotavirus infection when rabbits were challenged orally 28 days postinoculation (DPI) with 103 50% infective doses of ALA rabbit rotavirus. Other HRVs did not productively infect rabbits and provided no significant protection from challenge, in spite of occasional seroconversion. Simian RRV replicated as efficiently as lapine ALA rotavirus in rabbits and provided complete protection from ALA challenge. Live attenuated RRV reassortant vaccine strains resulted in no, limited, or productive infection of rabbits, but all rabbits were completely protected from heterotypic ALA challenge. The altered replication efficiency of the reassortants in rabbits suggests a role for VP7 in host range restriction. Also, our results suggest that VP4 may be involved in, but is not exclusively responsible for, host range restriction in the rabbit model. The replication efficiency of rotavirus in rabbits also is not controlled by the product of gene 5 (NSP1) alone, since a reassortant rotavirus with ALA gene 5 and all other genes from SA11 was more severely replication restricted than either parental rotavirus strain. PMID:9499095

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

PubMed

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

2016-06-30

Myxedema coma (MC) is a life-threatening endocrine crisis caused by severe hypothyroidism. However, validated diagnostic criteria and treatment guidelines for MC have not been established owing to its rarity. Therefore, a valid animal model is required to investigate the pathologic and therapeutic aspects of MC. The aim of the present study was to establish an animal model of MC induced by total thyroidectomy. We utilized 14 male New Zealand White rabbits anesthetized via intramuscular ketamine and xylazine administration. A total of 7 rabbits were completely thyroidectomized under a surgical microscope (thyroidectomized group) and the remainder underwent sham operations (control group). The animals in both groups were monitored without thyroid hormone replacement for 15 weeks. Pulse rate, blood pressure, body temperature, and electrocardiograms (ECG) were recorded and blood samples were taken from the jugular vein immediately prior to the thyroidectomy and 2 and 4 weeks after surgery. The thyroidectomized rabbits showed a marked reduction of serum thyroxine levels at 4 weeks after the surgical procedure vs. controls (0.50±0.10 vs. 3.32±0.68 μg/dL, p<0.001). Additionally, thyroidectomized rabbits exhibited several signs of hypothyroidism such as hypothermia, systolic hypotension, bradycardia, and low voltage on ECGs, compared with controls. Of the 7 rabbits with severe hypothyroidism, 6 died from 4 to 14 weeks after the thyroidectomy possibly owing to heart failure, because histopathologic examinations revealed a myxedema heart. In summary, we have established a rabbit model of fatal hypothyroidism mimicking MC, which may facilitate pathophysiological and molecular investigations of MC and evaluations of new therapeutic interventions.

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.

Ca(2+)-related signaling and protein phosphorylation abnormalities play central roles in a new experimental model of electrical storm.

PubMed

Tsuji, Yukiomi; Hojo, Mayumi; Voigt, Niels; El-Armouche, Ali; Inden, Yasuya; Murohara, Toyoaki; Dobrev, Dobromir; Nattel, Stanley; Kodama, Itsuo; Kamiya, Kaichiro

2011-05-24

Electrical storm (ES), characterized by recurrent ventricular tachycardia/fibrillation, typically occurs in implantable cardioverter-defibrillator patients and adversely affects prognosis. However, the underlying molecular basis is poorly understood. In the present study, we report a new experimental model featuring repetitive episodes of implantable cardioverter-defibrillator firing for recurrent ventricular fibrillation (VF), in which we assessed involvement of Ca(2+)-related protein alterations in ES. We studied 37 rabbits with complete atrioventricular block for ≈80 days, all with implantable cardioverter-defibrillator implantation. All rabbits showed long-QT and VF episodes. Fifty-three percent of rabbits developed ES (≥3 VF episodes per 24-hour period; 103±23 VF episodes per rabbit). Expression/phosphorylation of Ca(2+)-handling proteins was assessed in left ventricular tissues from rabbits with the following: ES; VF episodes but not ES (non-ES); and controls. Left ventricular end-diastolic diameter increased comparably in ES and non-ES rabbits, but contractile dysfunction was significantly greater in ES than in non-ES rabbits. ES rabbits showed striking hyperphosphorylation of Ca(2+)/calmodulin-dependent protein kinase II, prominent phospholamban dephosphorylation, and increased protein phosphatase 1 and 2A expression versus control and non-ES rabbits. Ryanodine receptors were similarly hyperphosphorylated at Ser2815 in ES and non-ES rabbits, but ryanodine receptor Ser2809 and L-type Ca(2+) channel α-subunit hyperphosphorylation were significantly greater in ES versus non-ES rabbits. To examine direct effects of repeated VF/defibrillation, VF was induced 10 times in control rabbits. Repeated VF tissues showed autophosphorylated Ca(2+)/calmodulin-dependent protein kinase II upregulation and phospholamban dephosphorylation like those of ES rabbit hearts. Continuous infusion of a calmodulin antagonist (W-7) to ES rabbits reduced Ca(2+)/calmodulin-dependent protein kinase II hyperphosphorylation, suppressed ventricular tachycardia/fibrillation, and rescued left ventricular dysfunction. ES causes Ca(2+)/calmodulin-dependent protein kinase II activation and phospholamban dephosphorylation, which can explain the vicious cycle of arrhythmia promotion and mechanical dysfunction that characterizes ES.

The KIT gene is associated with the english spotting coat color locus and congenital megacolon in Checkered Giant rabbits (Oryctolagus cuniculus).

PubMed

Fontanesi, Luca; Vargiolu, Manuela; Scotti, Emilio; Latorre, Rocco; Faussone Pellegrini, Maria Simonetta; Mazzoni, Maurizio; Asti, Martina; Chiocchetti, Roberto; Romeo, Giovanni; Clavenzani, Paolo; De Giorgio, Roberto

2014-01-01

The English spotting coat color locus in rabbits, also known as Dominant white spotting locus, is determined by an incompletely dominant allele (En). Rabbits homozygous for the recessive wild-type allele (en/en) are self-colored, heterozygous En/en rabbits are normally spotted, and homozygous En/En animals are almost completely white. Compared to vital en/en and En/en rabbits, En/En animals are subvital because of a dilated ("mega") cecum and ascending colon. In this study, we investigated the role of the KIT gene as a candidate for the English spotting locus in Checkered Giant rabbits and characterized the abnormalities affecting enteric neurons and c-kit positive interstitial cells of Cajal (ICC) in the megacolon of En/En rabbits. Twenty-one litters were obtained by crossing three Checkered Giant bucks (En/en) with nine Checkered Giant (En/en) and two en/en does, producing a total of 138 F1 and backcrossed rabbits. Resequencing all coding exons and portions of non-coding regions of the KIT gene in 28 rabbits of different breeds identified 98 polymorphisms. A single nucleotide polymorphism genotyped in all F1 families showed complete cosegregation with the English spotting coat color phenotype (θ=0.00 LOD  =75.56). KIT gene expression in cecum and colon specimens of En/En (pathological) rabbits was 5-10% of that of en/en (control) rabbits. En/En rabbits showed reduced and altered c-kit immunolabelled ICC compared to en/en controls. Morphometric data on whole mounts of the ascending colon showed a significant decrease of HuC/D (P<0.05) and substance P (P<0.01) immunoreactive neurons in En/En vs. en/en. Electron microscopy analysis showed neuronal and ICC abnormalities in En/En tissues. The En/En rabbit model shows neuro-ICC changes reminiscent of the human non-aganglionic megacolon. This rabbit model may provide a better understanding of the molecular abnormalities underlying conditions associated with non-aganglionic megacolon.

The KIT Gene Is Associated with the English Spotting Coat Color Locus and Congenital Megacolon in Checkered Giant Rabbits (Oryctolagus cuniculus)

PubMed Central

Fontanesi, Luca; Vargiolu, Manuela; Scotti, Emilio; Latorre, Rocco; Faussone Pellegrini, Maria Simonetta; Mazzoni, Maurizio; Asti, Martina; Chiocchetti, Roberto; Romeo, Giovanni; Clavenzani, Paolo; De Giorgio, Roberto

2014-01-01

The English spotting coat color locus in rabbits, also known as Dominant white spotting locus, is determined by an incompletely dominant allele (En). Rabbits homozygous for the recessive wild-type allele (en/en) are self-colored, heterozygous En/en rabbits are normally spotted, and homozygous En/En animals are almost completely white. Compared to vital en/en and En/en rabbits, En/En animals are subvital because of a dilated (“mega”) cecum and ascending colon. In this study, we investigated the role of the KIT gene as a candidate for the English spotting locus in Checkered Giant rabbits and characterized the abnormalities affecting enteric neurons and c-kit positive interstitial cells of Cajal (ICC) in the megacolon of En/En rabbits. Twenty-one litters were obtained by crossing three Checkered Giant bucks (En/en) with nine Checkered Giant (En/en) and two en/en does, producing a total of 138 F1 and backcrossed rabbits. Resequencing all coding exons and portions of non-coding regions of the KIT gene in 28 rabbits of different breeds identified 98 polymorphisms. A single nucleotide polymorphism genotyped in all F1 families showed complete cosegregation with the English spotting coat color phenotype (θ = 0.00 LOD  = 75.56). KIT gene expression in cecum and colon specimens of En/En (pathological) rabbits was 5–10% of that of en/en (control) rabbits. En/En rabbits showed reduced and altered c-kit immunolabelled ICC compared to en/en controls. Morphometric data on whole mounts of the ascending colon showed a significant decrease of HuC/D (P<0.05) and substance P (P<0.01) immunoreactive neurons in En/En vs. en/en. Electron microscopy analysis showed neuronal and ICC abnormalities in En/En tissues. The En/En rabbit model shows neuro-ICC changes reminiscent of the human non-aganglionic megacolon. This rabbit model may provide a better understanding of the molecular abnormalities underlying conditions associated with non-aganglionic megacolon. PMID:24736498

Safety and Efficacy of Topical Chitogel- Deferiprone-Gallium Protoporphyrin in Sheep Model

PubMed Central

Ooi, Mian L.; Richter, Katharina; Drilling, Amanda J.; Thomas, Nicky; Prestidge, Clive A.; James, Craig; Moratti, Stephen; Vreugde, Sarah; Psaltis, Alkis J.; Wormald, Peter-John

2018-01-01

Objectives: Increasing antimicrobial resistance has presented new challenges to the treatment of recalcitrant chronic rhinosinusitis fuelling a continuous search for novel antibiofilm agents. This study aimed to assess the safety and efficacy of Chitogel (Chitogel®, Wellington New Zealand) combined with novel antibiofilm agents Deferiprone and Gallium Protoporphyrin (CG-DG) as a topical treatment against S. aureus biofilms in vivo. Methods: To assess safety, 8 sheep were divided into two groups of 7 day treatments (n = 8 sinuses per treatment); (1) Chitogel (CG) with twice daily saline flush, and (2) CG-DG gel with twice daily saline flush. Tissue morphology was analyzed using histology and scanning electron microscopy (SEM). To assess efficacy we used a S. aureus sheep sinusitis model. Fifteen sheep were divided into three groups of 7 day treatments (n = 10 sinuses per treatment); (1) twice daily saline flush (NT), (2) Chitogel (CG) with twice daily saline flush, and (3) CG-DG gel with twice daily saline flush. Biofilm biomass across all groups was compared using LIVE/DEAD BacLight stain and confocal scanning laser microscopy. Results: Safety study showed no cilia denudation on scanning electron microscopy and no change in sinus mucosa histopathology when comparing CG-DG to CG treated sheep. COMSTAT2 assessment of biofilm biomass showed a significant reduction in CG-DG treated sheep compared to NT controls. Conclusion: Results indicate that CG-DG is safe and effective against S. aureus biofilms in a sheep sinusitis model and could represent a viable treatment option in the clinical setting.

Transcatheter closure of a sinus venosus atrial septal defect using 3D printing and image fusion guidance.

PubMed

Thakkar, Akanksha N; Chinnadurai, Ponraj; Breinholt, John P; Lin, C Huie

2018-06-13

A 63-year-old man with cirrhosis, hepatocellular carcinoma, and coagulopathy was diagnosed with a sinus venosus atrial septal defect (ASD) and partial anomalous pulmonary venous return (PAPVR) of the right upper pulmonary vein (RUPV). Transcatheter repair by positioning a stent graft in the superior vena cava was planned. Based on three-dimensional (3D) reconstruction of gated cardiac CTA, a 28 mm × 7 cm Endurant II ® aortic extension stent graft (Medtronic, MN) was chosen. A 3D model printed from the CTA was used to simulate device deployment, demonstrating successful exclusion of the sinus venosus ASD with return of the RUPV to the left atrium (LA). Post simulation, the 3D model was used for informed consent. The patient was then taken to the hybrid operating room. On-table cone beam CT was performed and registered with the CTA images. This enabled overlay of 3D regions of interest to live 2D fluoroscopy. The stent graft was then deployed using 3D regions of interest for guidance. Hemodynamics and angiography demonstrated successful exclusion of the sinus venosus ASD and unobstructed return of RUPV to the LA. This is the first report of comprehensive use of contemporary imaging for planning, simulation, patient consent, and procedural guidance for patient-centered complex structural intervention in repair of sinus venosus ASD with PAPVR. We propose this as a process model for continued innovation in structural interventions. © 2018 The Authors Catheterization and Cardiovascular Interventions Published by Wiley Periodicals, Inc.

Safety and Efficacy of Topical Chitogel- Deferiprone-Gallium Protoporphyrin in Sheep Model.

PubMed

Ooi, Mian L; Richter, Katharina; Drilling, Amanda J; Thomas, Nicky; Prestidge, Clive A; James, Craig; Moratti, Stephen; Vreugde, Sarah; Psaltis, Alkis J; Wormald, Peter-John

2018-01-01

Objectives: Increasing antimicrobial resistance has presented new challenges to the treatment of recalcitrant chronic rhinosinusitis fuelling a continuous search for novel antibiofilm agents. This study aimed to assess the safety and efficacy of Chitogel (Chitogel®, Wellington New Zealand) combined with novel antibiofilm agents Deferiprone and Gallium Protoporphyrin (CG-DG) as a topical treatment against S. aureus biofilms in vivo . Methods: To assess safety, 8 sheep were divided into two groups of 7 day treatments ( n = 8 sinuses per treatment); (1) Chitogel (CG) with twice daily saline flush, and (2) CG-DG gel with twice daily saline flush. Tissue morphology was analyzed using histology and scanning electron microscopy (SEM). To assess efficacy we used a S. aureus sheep sinusitis model. Fifteen sheep were divided into three groups of 7 day treatments ( n = 10 sinuses per treatment); (1) twice daily saline flush (NT), (2) Chitogel (CG) with twice daily saline flush, and (3) CG-DG gel with twice daily saline flush. Biofilm biomass across all groups was compared using LIVE/DEAD BacLight stain and confocal scanning laser microscopy. Results: Safety study showed no cilia denudation on scanning electron microscopy and no change in sinus mucosa histopathology when comparing CG-DG to CG treated sheep. COMSTAT2 assessment of biofilm biomass showed a significant reduction in CG-DG treated sheep compared to NT controls. Conclusion: Results indicate that CG-DG is safe and effective against S. aureus biofilms in a sheep sinusitis model and could represent a viable treatment option in the clinical setting.

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

PubMed

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

2011-01-01

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

Crestal Sinus Augmentation in the Presence of Severe Sinus Mucosal Thickening: A Report of 3 Cases.

PubMed

Fang, Yiqin; An, Xueyin; Jeong, Seung-Mi; Choi, Byung-Ho

2018-06-01

In the presence of severe sinus mucosal thickening, the ostium can be blocked when the sinus membrane is lifted, causing drainage disturbances and sinusitis. Here, we present 3 cases in which maxillary sinus floor elevation was performed using a crestal approach in the presence of severe sinus mucosal thickening (>10 mm). The effects of maxillary sinus floor elevation using the crestal approach technique on sinus mucosal thickening and bone formation in the sinus were evaluated using cone beam computed tomography. None of the patients exhibited an increase in sinus membrane thickness. No complications were encountered during the follow-up periods, and bone formation was observed around the implants at the sinus floor. All implants were functioning successfully. Maxillary sinus floor elevation using the crestal approach technique in the presence of severe sinus mucosal thickening allows for minimally invasive sinus grafting and simultaneous implant placement and does not increase sinus membrane thickness.

Use of an Active-Fixation Coronary Sinus Lead to Implant a Biventricular Pacemaker via the Femoral Vein

PubMed Central

Shandling, Adrian; Donohue, Daniel; Tobias, Serge; Wu, Iris; Brar, Ramandeep

2010-01-01

Cardiac resynchronization therapy, which involves the placement of a pacing lead in the right atrium and in each ventricle, is effective in treating heart failure that is caused by left bundle branch block and cardiomyopathy. The left ventricular lead is usually placed into a lateral branch of the coronary sinus via the subclavian route. When the subclavian route is unavailable, insertion of a standard, passive-fixation coronary sinus lead via the femoral approach is feasible; however, the likelihood of subsequent dislodgment is high. Herein, we describe the placement of a novel, self-retaining, active-fixation coronary sinus lead—the Attain StarFix® Model 4195 OTW Lead—in an elderly heart-failure patient, via the femoral approach. We believe that this is the 1st report of this procedure. PMID:20200636

Atrioventricular node functional remodeling induced by atrial fibrillation.

PubMed

Zhang, Youhua; Mazgalev, Todor N

2012-09-01

The atrioventricular node (AVN) plays a vital role in determining the ventricular rate during atrial fibrillation (AF). AF results in profound electrophysiological and structural remodeling in the atria as well as the sinus node. However, it is unknown whether AVN undergoes remodeling during AF. To determine whether AVN undergoes functional remodeling during AF. AVN conduction properties were studied in vitro in 9 rabbits with AF and 10 normal controls. A previously validated index of AVN dual-pathway electrophysiology, His-electrogram alternans, was used to monitor fast-pathway or slow-pathway (SP) AVN conduction in these experiments. AVN conduction properties were further studied in vivo in 7 dogs with chronic AF and 8 controls. Compared with the control rabbits, the rabbits with AF had a longer AVN conduction time (83 ± 16 ms vs 68 ± 7 ms; P <.01), longer AVN effective refractory period (141 ± 27 ms vs 100 ± 9 ms; P <.01), an earlier transition from fast-pathway to SP conduction (at a longer prematurity, 249 ± 60 ms vs 171 ± 24 ms; P <.01), and a slower ventricular rate during simulated AF (RR interval 249 ± 42 ms vs 202 ± 12 ms; P <.01). Notably, a larger proportion of conducted beats utilized the SP in AF preparations (92% ± 12% vs 63% ± 32%; P <.05). Long-term AF in dogs resulted in a longer atrioventricular conduction time and AVN effective refractory period and a slower ventricular rate during AF compared with the controls. Pronounced AVN functional electrophysiological remodeling occurs after long-term AF, which could lead to a spontaneous slowing of the ventricular rate. Furthermore, the SP dominance during AF underscores the effectiveness of its modification by ablation for ventricular rate control during AF. Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

An Animal Model for Human EBV-Associated Hemophagocytic Syndrome

PubMed Central

Hayashi, Kazuhiko; Ohara, Nobuya; Teramoto, Norihiro; Onoda, Sachiyo; Chen, Hong-Li; Oka, Takashi; Kondo, Eisaku; Yoshino, Tadashi; Takahashi, Kiyoshi; Yates, John; Akagi, Tadaatsu

2001-01-01

Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS) is often associated with fatal infectious mononucleosis. However, the animal model for EBV-AHS has not been developed. We reported the first animal model for EBV-AHS using rabbits infected with EBV-related herpesvirus of baboon (HVP). Eleven of 13 (85%) rabbits inoculated intravenously with HVP-producing cells developed fatal lymphoproliferative disorders (LPD) between 22 and 105 days after inoculation. LPD was also accompanied by hemophagocytic syndrome (HPS) in nine of these 11 rabbits. The peroral spray of cell-free HVP induced the virus infection with increased anti-EBV-viral capsid antigen-IgG titers in three of five rabbits, and two of these three infected rabbits died of LPD with HPS. Autopsy revealed hepatosplenomegaly and swollen lymph nodes. Atypical lymphoid T cells expressing EBV-encoded small RNA-1 infiltrated diffusely in many organs, frequently involving the lymph nodes, spleen, and liver. Hemophagocytic histiocytosis was observed in the lymph nodes, spleen, bone marrow, and thymus. HVP-DNA was detected in the tissues and peripheral blood from the infected rabbits by polymerase chain reaction or Southern blot analysis. Reverse transcriptase-polymerase chain reaction revealed both HVP-EBNA1 and HVP-EBNA2 transcripts, suggesting latency type III infection. These data indicate that the high rate of rabbit LPD with HPS induction is caused by HVP. This system is useful for studying the pathogenesis, prevention, and treatment of human EBV-AHS. PMID:11290571

Biodegradable nanofiber-membrane for sustainable release of lidocaine at the femoral fracture site as a periosteal block: In vitro and in vivo studies in a rabbit model.

PubMed

Chou, Ying-Chao; Cheng, Yi-Shiun; Hsu, Yung-Heng; Yu, Yi-Hsun; Liu, Shih-Jung

2016-04-01

The aim of this study was to evaluate the efficacy of a biodegradable, lidocaine-embedded, nanofibrous membrane for the sustainable analgesic release onto fragments of a segmental femoral fracture site. Membranes of three different lidocaine concentrations (10%, 30%, and 50%) were produced via an electrospinning technique. In vitro lidocaine release was assessed by high-performance liquid chromatography. A femoral segmental fracture, with intramedullary Kirschner-wire fixation and polycaprolactone stent enveloping the fracture site, was set-up in a rabbit model for in vivo assessment of post-operative recovery of activity. Eighteen rabbits were randomly assigned to three groups (six rabbits per group): group A comprised of rabbits with femoral fractures and underwent fixation; group B comprised of a comparable fracture model to that of group A with the implantation of lidocaine-loaded nanofibers; and group C, the control group, received only anesthesia. The following variables were measured: change in body weight, food and water intake before and after surgery, and total activity count post-surgery. All membranes eluted effective levels of lidocaine for more than 3 weeks post-surgery. Rabbits in group B showed faster recovery of activity post-operatively, compared with those in group A, which confirmed the pain relief efficacy of the lidocaine-embedded nanofibers. Nanofibers with sustainable lidocaine release have adequate efficacy and durability for pain relief in rabbits with segmental long bone fractures. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed

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

2016-10-01

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

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.

Local hyperthermia for esophageal cancer in a rabbit tumor model: Magnetic stent hyperthermia versus magnetic fluid hyperthermia

PubMed Central

LIU, JIAYI; LI, NING; LI, LI; LI, DANYE; LIU, KAI; ZHAO, LINGYUN; TANG, JINTIAN; LI, LIYA

2013-01-01

Magnetic-mediated hyperthermia (MMH) is a promising local thermotherapy approach for cancer treatment. The present study investigated the feasibility and effectiveness of MMH in esophageal cancer using a rabbit tumor model. The therapeutic effect of two hyperthermia approaches, magnetic stent hyperthermia (MSH), in which heat is induced by the clinical stent that is placed inside the esophagus, and magnetic fluid hyperthermia (MFH), where magnetic nanoparticles are applied as the agent, was systematically evaluated. A rabbit esophageal tumor model was established by injecting VX2 carcinoma cells into the esophageal submucosa. The esophageal stent was deployed perorally into the tumor segment of the esophagus. For the MFH, magnetic nanoparticles (MNPs) were administered to the rabbits by intratumoral injection. The rabbits were exposed under a benchtop applicator using an alternative magnetic field (AMF) with 300 kHz frequency for the hyperthermia treatment. The results demonstrated that esophageal stents and MNPs had ideal inductive heating properties upon exposure under an AMF of 300 kHz. MSH, using a thermal dose of 46°C with a 10-min treatment time, demonstrated antitumor effects on the rabbit esophageal cancer. However, the rabbit esophageal wall is not heat-resistant. Therefore, a higher temperature or longer treatment time may lead to necrosis of the rabbit esophagus. MFH has a significant antitumor effect by confining the heat within the tumor site without damaging the adjacent normal tissues. The present study indicates that the two hyperthermia procedures have therapeutic effects on esophageal cancer, and that MFH may be more specific than MSH in terms of temperature control during the treatment. PMID:24260045

Augmentation of Chemotherapeutic Infusion Effect by TSU-68, an Oral Targeted Antiangiogenic Agent, in a Rabbit VX2 Liver Tumor Model

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

Kim, Hyo-Cheol; Chung, Jin Wook, E-mail: chungjw@snu.ac.kr; Choi, Seung Hong

Purpose: This study was designed to investigate the in vivo effects of combination therapy with TSU-68 and chemotherapeutic infusion in a rabbit VX2 liver tumor model. Methods: This study was approved by the animal care committee at our institute. Three weeks before chemotherapeutic infusion, VX2 carcinoma was implanted into the livers of 32 rabbits. One week after chemotherapeutic infusion, vehicle was administered orally for 3 weeks in the control group (n = 16), and TSU-68 was administered orally at a daily dose of 200 mg/kg for 3 weeks in the treated group (n = 16). Computed tomography (CT) was performedmore » before and 1, 2, 3, and 4 weeks after chemotherapeutic infusion. Tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) on CT scan. The maximum thickness of viable tumor was measured on microscopic sections. Results: According to the RECIST, stable disease was observed in 9 (56%) rabbits and progressive disease in 7 (44%) in the control group, whereas partial response was observed in 1 (6%) rabbit and stable disease in 15 (94%) in the treated group. On pathologic examination, a viable lesion was present in 12 (75%) rabbits in the control group and in 6 (38%) rabbits in the treated group (P = 0.073). The mean maximum thickness of viable tumor in the treated group was significantly smaller than that in the control group (0.74 mm vs. 3.39 mm; P = 0.02). Conclusions: Oral administration of TSU-68 augmented the effect of chemotherapeutic infusion in a rabbit VX2 liver tumor model.« less

Successful Treatment of Passive Fecal Incontinence in an Animal Model Using Engineered Biosphincters: A 3‐Month Follow‐Up Study

PubMed Central

Bohl, Jaime L.; Zakhem, Elie

2017-01-01

Abstract Fecal incontinence (FI) is the involuntary passage of fecal material. Current treatments have limited successful outcomes. The objective of this study was to develop a large animal model of passive FI and to demonstrate sustained restoration of fecal continence using anorectal manometry in this model after implantation of engineered autologous internal anal sphincter (IAS) biosphincters. Twenty female rabbits were used in this study. The animals were divided into three groups: (a) Non‐treated group: Rabbits underwent IAS injury by hemi‐sphincterectomy without treatment. (b) Treated group: Rabbits underwent IAS injury by hemi‐sphincterectomy followed by implantation of autologous biosphincters. (c) Sham group: Rabbits underwent IAS injury by hemi‐sphincterectomy followed by re‐accessing the surgical site followed by immediate closure without implantation of biosphincters. Anorectal manometry was used to measure resting anal pressure and recto‐anal inhibitory reflex (RAIR) at baseline, 1 month post‐sphincterectomy, up to 3 months after implantation and post‐sham. Following sphincterectomy, all rabbits had decreased basal tone and loss of RAIR, indicative of FI. Anal hygiene was also lost in the rabbits. Decreases in basal tone and RAIR were sustained more than 3 months in the non‐treated group. Autologous biosphincters were successfully implanted into eight donor rabbits in the treated group. Basal tone and RAIR were restored at 3 months following biosphincter implantation and were significantly higher compared with rabbits in the non‐treated and sham groups. Histologically, smooth muscle reconstruction and continuity was restored in the treated group compared with the non‐treated group. Results in this study provided promising outcomes for treatment of FI. Results demonstrated the feasibility of developing and validating a large animal model of passive FI. This study also showed the efficacy of the engineered biosphincters to restore fecal continence as demonstrated by manometry. Stem Cells Translational Medicine 2017;6:1795–1802 PMID:28678378

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

PubMed

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

2013-03-01

Ischemic/reperfusion (I/R) injury of the spinal cord is a serious complication that can result from thoracoabdominal aortic surgery. To investigate the neuroprotective effect of curcumin against I/R injury in a rabbit model. A total of 36 rabbits were randomly divided into three groups: sham, I/R, and curcumin-treated group. Rabbits were subject to 30-min aortic occlusion to induce transient spinal cord ischemia. Neurological function was observed after reperfusion and spinal cord segment (L3-L5) was collected for histopathological evaluation. Malondialdehyde (MDA) and total superoxide dismutase (SOD) activity were also assayed. Rabbits in I/R group were induced to paraplegia. While after 48-hour treatment, compared with I/R group, curcumin significantly improved neurological function, reduced cell apoptosis and MDA levels as well as increased SOD activity (P < 0.05). The results suggest that curcumin, at least in an animal model, can attenuate transient spinal cord ischemic injury potentially via reducing oxidative damage, which may provide a novel approach in the treatment of spinal cord ischemic injury.

[Radiographic study of maxillary sinus associated with molars in adult].

PubMed

Hu, Zhi; Sun, Daming; Zhou, Quansheng; Wang, Yuli; Gu, Jingcheng; Han, Yaohua

2014-12-01

to explore the relationship between the maxillary sinus volume and the amount of alveolar bone, and the effect of molar loss upon the maxillary sinus was further analyzed,by measuring adult maxillary sinus volume, sinus ridge distance, and calculating the gasification coefficient of maxillary sinus. One hundred and ninety cases (361 maxillary sinus) with CT examinations were collected, they were divided into group A and group B, 121 cases (242 maxillary sinus) of normal subjects served as group A, 42 cases (65 maxillary sinus) with molar part off were B group, in which 31 maxillary sinus with a molar loss were group B1,22 maxillary sinus with two molar loss were B2 group,12 maxillary sinus with three molar loss (one molar remains) were B3 group, 27 cases (54 maxillary sinus) with upper teeth off were C group. Bymeasureing the maxillary sinus volume, sinus ridge distance and the size of the maxillary sinus, calculating the gasification coefficient, we analyzed the relationship between maxillary volume and sinus ridge distance, and comparatively analyzed the differences among the three groups in the size, gasification coefficient, volume of maxillary sinus and sinus ridge distance. In the normal group,the volume of maxillary sinus and sinus ridge distance had a correlation coefficient of -0. 63,(P< 0.05); Sinus ridge distance in group A was larger than the other two groups (P<0.05), and larger in B group than in C group (P<0. 05), anteroposterior maxillary sinus diameter and reft-right diameter in C group was greater than in A group and B group(P<0.05), group C gasification coeffiecent was less than A group and B group (P<0. 05). The volume of maxillary sinus is negatively correlated with the amont of alveolar bone; Upper teeth's shedding promotes maxillary sinus deformation; Maxiuary sinus volume has a tendency to decrease.

Influence of the site of origin on the outcome of squamous cell carcinoma of the maxilla-oral versus sinus.

PubMed

Bobinskas, A M; Wiesenfeld, D; Chandu, A

2014-02-01

The maxilla may be affected by squamous cell carcinoma (SCC) from both oral and sinus sites. We sought to determine whether the site of origin of the maxillary tumour, oral as compared to sinus, influences survival. Univariate Kaplan-Meier and multivariate Cox proportional hazard models analysis of 58 patients with SCC involving the maxilla, treated with curative intent, was conducted. The overall 5-year disease-free survival for the group was 41.7%. Five-year disease-free survival for oral subsite SCC was 56.8%, while for sinus subsite was only 21.6%. Univariate analysis found SCC of sinus origin to be associated with a poorer prognosis, however this was not confirmed on multivariate analysis. T-stage and positive margins were found to be the only independent risk factors. For SCC of the maxilla, sinus origin of the tumour per se does not confer a poorer prognosis; however, as a result of the complex anatomy of the midface, these tumours can present at an advanced stage, while surgical control of the disease can be more difficult, especially posteriorly. Tumour size and positive margins were the determinants of a poor prognosis in this group of patients with maxillary SCC. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

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

PubMed

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

2018-04-01

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

Volumetric velocimetry downstream of a percutaneous heart valve

NASA Astrophysics Data System (ADS)

Raghav, Vrishank; Clifford, Christopher; Midha, Prem; Okafor, Ikechukwu; Thurow, Brian; Yoganathan, Ajit; Auburn University Collaboration; Georgia Institute of Technology Collaboration

2017-11-01

Transcatheter aortic valve replacement has emerged as a safe and effective treatment for severe, symptomatic aortic stenosis in intermediate or greater surgical risk patients. However, despite excellent short-term outcomes, improved imaging and awareness has led to the identification of leaflet thrombosis on the aortic side of the prosthesis. Upon implantation, the transcatheter heart valve (THV) becomes enclosed in the native aortic valve leaflet tissue dividing the native sinus into two regions - a smaller anatomical sinus and a neo-sinus. To understand the causes for thrombosis, plenoptic Particle Image Velocimetry (PIV) is used to investigate the pulsatile three-dimensional flow in the sinus and neo-sinus region of the THV. Experiments are conducted on both a real and a transparent THV model in a pulsatile flow loop capable of replicating physiological hemodynamics. Comparisons with planar PIV results demonstrate the feasibility of using Plenoptic PIV to study heart valve fluid dynamics. Large three-dimensional regions of low velocity magnitude and low viscous shear stress were observed near the heart valve which could increase particle residence time potentially leading to formation of clots the THV leaflet.

The paranasal sinuses: the last frontier in craniofacial biology.

PubMed

Márquez, Samuel

2008-11-01

This special issue of the Anatomical Record explores the presence and diversity of paranasal sinuses in distinct vertebrate groups. The following topics are addressed in particular: dinosaur physiology; development; physiology; adaptation; imaging; and primate systematics. A variety of approaches and techniques are used to examine and characterize the diversity of paranasal sinus pneumatization in a wide spectrum of vertebrates. These range from dissection to histology, from plain X-rays to computer tomography, from comparative anatomy to natural experimental settings, from mathematical computation to computer model simulation, and 2D to 3D reconstructions. The articles in this issue are a combination of literature review and new, hypothesis-driven anatomical research that highlights the complexities of paranasal sinus growth and development; ontogenetic and disease processes; physiology; paleontology; primate systematics; and human evolution. The issue incorporates a wide variety of vertebrates, encompassing a period of over 65 million years, in an effort to offer insight into the diversity of the paranasal sinus complexes through time and space, and thereby providing a greater understanding and appreciation of these special spaces within the cranium. Copyright 2008 Wiley-Liss, Inc.

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

PubMed

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

2016-10-12

To observe the influence of different methods of moxibustion on spleen morphology in cyclophosphamide-induced immunosuppressive rabbits. A total of 50 rabbits were randomly assigned into a blank group, a model group, a herbal cake-separated moxibustion group, a moxibustion group and a sham cake-separated moxibustion group, 10 rabbits in each group. Except the blank group, the rabbits in each group were treated with intraperitoneal injection of cyclophosphamide (60 mg/kg), once a day, for 7 consecutive days to establish immunosuppressive model. After the model establishment, the rabbits in the herbal cake-separated moxibustion group were treated with herbal cake-separated moxibustion at "Shenque" (CV 8), "Guanyuan" (CV 4), "Zusanli" (ST 36), "Pishu" (BL 20) and "Shenshu" (BL 23); the moxa cone was placed on the herbal cake which was made of Liuwei Dihuang decoction, three cones for each acupoint. The rabbits in the moxibustion group were treated with moxa stick moxibustion which contained equal moxa of three moxa cones. The rabbits in the sham cake-separated moxibustion group were treated with cake which was made of flour. The acupoint selection in the above three groups was identical, and the intervention was given once every other day for totally 10 times. The rabbits in the blank group and model group were immobilized for identical time without any intervention. After treatment, the rabbits were sacrificed to collect the spleen. With routine HE staining, the morphology changes of spleen were observed under microscope. In addition, the white pulp, splenic corpuscle and the counts of lymphatic cells of lymphatic sheath around the arteries were observed. Compared with the blank group, the average size of white pulp and the radius of splenic corpuscle were reduced (both P <0.01), and the lymphatic cells of lymphatic sheath around the arteries were significantly decreased in the model group ( P <0.01), but the counts of splenic nodule were increased without significant difference ( P >0.05). Compared with the model group, the averagesize of white pulp and the radius of splenic corpuscle were significantly increased in the herbal cake-separated moxibustion group and moxibustion group (all P <0.01). The lymphatic cells of lymphatic sheath around the arteries were significantly increased in the herbal cake-separated moxibustion group and sham cake-separated moxibustion group (both P <0.01). Compared with the moxibustion group, the count of lymphatic cells of lymphatic sheath around the arteries was increased in the herbal cake-separated moxibustion ( P <0.01). Compared with the sham cake-separated moxibustion group, the radius of splenic corpuscle was significant increased in the herbal cake-separated moxibustion group ( P <0.01). The improvement of herbal cake-separated moxibustion on immunologic function is superior to moxibustion and sham cake-separated moxibustion in cyclophosphamide-induced rabbits.

A comparative study of the regenerative effect of sinus bone grafting with platelet-rich fibrin-mixed Bio-Oss® and commercial fibrin-mixed Bio-Oss®: an experimental study.

PubMed

Xuan, Feng; Lee, Chun-Ui; Son, Jeong-Seog; Jeong, Seung-Mi; Choi, Byung-Ho

2014-06-01

Anorganic bovine bone (Bio-Oss®) particles are one of the most popular grafting materials. The particles are often mixed with platelet-rich fibrin (PRF) or a commercial fibrin (Tisseel®) to form a mouldable graft material. The objective of this study was to compare the potentials of PRF-mixed Bio-Oss® and Tisseel®-mixed Bio-Oss® to enhance bone regeneration in a canine sinus model. Six mongrel dogs were used in this study. After elevating the sinus membrane in both maxillary sinus cavities, an implant was placed into the sinus cavity. In one of the sinus cavities, the PRF/Bio-Oss® composite was grafted, and the Tisseel®/Bio-Oss® composite was grafted in the other sinus cavity. After a 6 month healing period, bone formation in the graft sites and bone-implant contact were evaluated. The mean osseointegration rate was 43.5 ± 12.4% and new bone formation rate 41.8 ± 5.9% in the PRF/Bio-Oss® composite sites. In the Tisseel®/Bio-Oss® composite sites they were 30.7 ± 7.9% and 31.3 ± 6.4%. There were statistically significant differences between the groups. The findings from this study suggest that when platelet-rich fibrin is used as an adjunct to Bio-Oss® particles for bone augmentation in the maxillary sinus, bone formation in the graft sites is significantly greater than when Tisseel® is used. Copyright © 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

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 distribution of bone layer and the mechanical properties of the femur of adult osteoarthritic rabbits.

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.

Co-occurrence dynamics of endangered Lower Keys marsh rabbits and free-ranging domestic cats: Prey responses to an exotic predator removal program.

PubMed

Cove, Michael V; Gardner, Beth; Simons, Theodore R; O'Connell, Allan F

2018-04-01

The Lower Keys marsh rabbit ( Sylvilagus palustris hefneri ) is one of many endangered endemic species of the Florida Keys. The main threats are habitat loss and fragmentation from sea-level rise, development, and habitat succession. Exotic predators such as free-ranging domestic cats ( Felis catus ) pose an additional threat to these endangered small mammals. Management strategies have focused on habitat restoration and exotic predator control. However, the effectiveness of predator removal and the effects of anthropogenic habitat modifications and restoration have not been evaluated. Between 2013 and 2015, we used camera traps to survey marsh rabbits and free-ranging cats at 84 sites in the National Key Deer Refuge, Big Pine Key, Florida, USA. We used dynamic occupancy models to determine factors associated with marsh rabbit occurrence, colonization, extinction, and the co-occurrence of marsh rabbits and cats during a period of predator removal. Rabbit occurrence was positively related to freshwater habitat and patch size, but was negatively related to the number of individual cats detected at each site. Furthermore, marsh rabbit colonization was negatively associated with relative increases in the number of individual cats at each site between survey years. Cat occurrence was negatively associated with increasing distance from human developments. The probability of cat site extinction was positively related to a 2-year trapping effort, indicating that predator removal reduced the cat population. Dynamic co-occurrence models suggested that cats and marsh rabbits co-occur less frequently than expected under random conditions, whereas co-detections were site and survey-specific. Rabbit site extinction and colonization were not strongly conditional on cat presence, but corresponded with a negative association. Our results suggest that while rabbits can colonize and persist at sites where cats occur, it is the number of individual cats at a site that more strongly influences rabbit occupancy and colonization. These findings indicate that continued predator management would likely benefit endangered small mammals as they recolonize restored habitats.

Development and validation of a physiology-based model for the prediction of pharmacokinetics/toxicokinetics in rabbits

PubMed Central

Hermes, Helen E.; Teutonico, Donato; Preuss, Thomas G.; Schneckener, Sebastian

2018-01-01

The environmental fates of pharmaceuticals and the effects of crop protection products on non-target species are subjects that are undergoing intense review. Since measuring the concentrations and effects of xenobiotics on all affected species under all conceivable scenarios is not feasible, standard laboratory animals such as rabbits are tested, and the observed adverse effects are translated to focal species for environmental risk assessments. In that respect, mathematical modelling is becoming increasingly important for evaluating the consequences of pesticides in untested scenarios. In particular, physiologically based pharmacokinetic/toxicokinetic (PBPK/TK) modelling is a well-established methodology used to predict tissue concentrations based on the absorption, distribution, metabolism and excretion of drugs and toxicants. In the present work, a rabbit PBPK/TK model is developed and evaluated with data available from the literature. The model predictions include scenarios of both intravenous (i.v.) and oral (p.o.) administration of small and large compounds. The presented rabbit PBPK/TK model predicts the pharmacokinetics (Cmax, AUC) of the tested compounds with an average 1.7-fold error. This result indicates a good predictive capacity of the model, which enables its use for risk assessment modelling and simulations. PMID:29561908

Keratoprosthesis: preliminary results of an artificial corneal button as a full-thickness implant in the rabbit model.

PubMed

Hicks, C R; Chirila, T V; Dalton, P D; Clayton, A B; Vijayasekaran, S; Crawford, G J; Constable, I J

1996-08-01

To develop a prototype artificial cornea and evaluate it in the rabbit model. Hydrogel core-and-skirt keratoprostheses were made and were inserted as full-thickness implants covered with conjunctival flaps in the right eyes of eight rabbits. Peroperative complications related to inadequate mechanical strength led to failure in the early postoperative period in three animals, one was euthanased for an unrelated reason and the remaining four have been successful for up to 16 weeks' follow-up. Full-thickness implantation of an artificial cornea, analogous to penetrating keratoplasty, has been achieved in the rabbit model. Histological findings confirm that integration of the prosthesis with host tissue occurs. The main complications encountered in this preliminary series were related to inadequate strength of the sponge skirt of this prototype device. Work in our laboratories is now concentrated upon improving the mechanical qualities of the hydrogel skirt and on the enhancement of biointegration.

Streptococcus faecium M 74 in control of diarrhoea induced by a human enterotoxigenic Escherichia coli strain in an infant rabbit model.

PubMed

Wadström, T

1984-08-01

Streptococcus faecium strain M 74 was evaluated as a prophylacticum for enterotoxigenic Escherichia coli (ETEC) diarrhoea with human isolates of E. coli with CFA/I and CFA/II surface fimbrial haemagglutinins (adhesins) in a rabbit model. Young rabbits (3 to 4 days old) were given S. faecium organisms (5 X 10(9)) 15 min before (group A), 6 h before (group B) and 12 h after (group C) challenge with ETEC organisms. Only 4 out of 26 rabbits in group A, 6 out of 21 in group B and 7 out of 23 in group C developed diarrhoea. In conclusion, this S. faecium strain M 74 seems efficiently to protect animals from ETEC diarrhoea when given as a prophylactic agent at a high dose. This animal model seems useful for comparative studies on new preventive methods for ETEC diarrhoea such as testing probiotics and antiadhesive drugs.

Inhalational anthrax (Ames aerosol) in naïve and vaccinated New Zealand rabbits: characterizing the spread of bacteria from lung deposition to bacteremia

PubMed Central

Gutting, Bradford W.; Nichols, Tonya L.; Channel, Stephen R.; Gearhart, Jeffery M.; Andrews, George A.; Berger, Alan E.; Mackie, Ryan S.; Watson, Brent J.; Taft, Sarah C.; Overheim, Katie A.; Sherwood, Robert L.

2012-01-01

There is a need to better understand inhalational anthrax in relevant animal models. This understanding could aid risk assessment, help define therapeutic windows, and provide a better understanding of disease. The aim here was to characterize and quantify bacterial deposition and dissemination in rabbits following exposure to single high aerosol dose (> 100 LD50) of Bacillus anthracis (Ames) spores immediately following exposure through 36 h. The primary goal of collecting the data was to support investigators in developing computational models of inhalational anthrax disease. Rabbits were vaccinated prior to exposure with the human vaccine (Anthrax Vaccine Adsorbed, AVA) or were sham-vaccinated, and were then exposed in pairs (one sham and one AVA) so disease kinetics could be characterized in equally-dosed hosts where one group is fully protected and is able to clear the infection (AVA-vaccinated), while the other is susceptible to disease, in which case the bacteria are able to escape containment and replicate uncontrolled (sham-vaccinated rabbits). Between 4–5% of the presented aerosol dose was retained in the lung of sham- and AVA-vaccinated rabbits as measured by dilution plate analysis of homogenized lung tissue or bronchoalveolar lavage (BAL) fluid. After 6 and 36 h, >80% and >96%, respectively, of the deposited spores were no longer detected in BAL, with no detectable difference between sham- or AVA-vaccinated rabbits. Thereafter, differences between the two groups became noticeable. In sham-vaccinated rabbits the bacteria were detected in the tracheobronchial lymph nodes (TBLN) 12 h post-exposure and in the circulation at 24 h, a time point which was also associated with dramatic increases in vegetative CFU in the lung tissue of some animals. In all sham-vaccinated rabbits, bacteria increased in both TBLN and blood through 36 h at which point in time some rabbits succumbed to disease. In contrast, AVA-vaccinated rabbits showed small numbers of CFU in TBLN between 24 and 36 h post-exposure with small numbers of bacteria in the circulation only at 24 h post-exposure. These results characterize and quantify disease progression in naïve rabbits following aerosol administration of Ames spores which may be useful in a number of different research applications, including developing quantitative models of infection for use in human inhalational anthrax risk assessment. PMID:22919678

Hierarchical spatial models for predicting pygmy rabbit distribution and relative abundance

USGS Publications Warehouse

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

2010-01-01

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

Gel-Sinuplasty for Chronic Rhinosinusitis With and Without Nasal Polyposis

ClinicalTrials.gov

2018-03-13

Chronic Sinusitis, Ethmoidal; Chronic Sinusitis - Ethmoidal Anterior; Chronic Sinusitis; Chronic Sinusitis - Ethmoidal, Posterior; Chronic Sinusitis, Sphenoidal; Chronic Sinusitis - Frontoethmoidal; Nasal Polyps; Nasal Polyp - Posterior

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

Anatomical Details of the Rabbit Nasal Passages and Their Implications in Breathing, Air Conditioning, and Olfaction

PubMed Central

Si, Xiuhua April; Kim, JongWon; Zhang, Yu; Jacob, Richard E.; Kabilan, Senthil; Corley, Richard A.

2016-01-01

The rabbit is commonly used as a laboratory animal for inhalation toxicology tests and detail knowledge of the rabbit airway morphometry is needed for outcome analysis or theoretical modeling. The objective of this study is to quantify the morphometric dimension of the nasal airway of a New Zealand white rabbit and to relate the morphology and functions through analytical and computational methods. Images of high-resolution MRI scans of the rabbit were processed to measure the axial distribution of the cross-sectional areas, perimeter, and complexity level. The lateral recess, which has functions other than respiration or olfaction, was isolated from the nasal airway and its dimension was quantified separately. A low Reynolds number turbulence model was implemented to simulate the airflow, heat transfer, vapor transport, and wall shear stress. Results of this study provide detailed morphological information of the rabbit that can be used in the studies of olfaction, inhalation toxicology, drug delivery, and physiology-based pharmacokinetics modeling. For the first time, we reported a spiral nasal vestibule that splits into three paths leading to the dorsal meatus, maxilloturbinate, and ventral meatus, respectively. Both non-dimensional functional analysis and CFD simulations suggested that the airflow in the rabbit nose is laminar and the unsteady effect is only significantly during sniffing. Due to the large surface-to-volume ratio, the maxilloturbinate is highly effective in warming and moistening the inhaled air to body conditions. The unique anatomical structure and respiratory airflow pattern may have important implications for designing new odorant detectors or electronic noses. PMID:27145450

A rabbit dry eye model induced by topical medication of a preservative benzalkonium chloride.

PubMed

Xiong, Cuiju; Chen, Dong; Liu, Jingbo; Liu, Bingqian; Li, Naiyang; Zhou, Yang; Liang, Xuanwei; Ma, Ping; Ye, Chengtian; Ge, Jian; Wang, Zhichong

2008-05-01

To establish a rabbit dry eye model with topical medication of the ocular preparation preservative benzalkonium chloride (BAC). Sixteen white rabbits were used. One eye of each rabbit was chosen randomly for topical administration of 0.1% BAC twice daily for 14 days. The other untreated eyes served as controls. Schirmer test, fluorescein, and rose bengal staining were performed before and after BAC treatment on days 3, 5, 7, and 14. Conjunctiva impression cytology specimens were collected on days 0, 7, and 14. The rabbits were killed after day 14. Immunofluorescence staining was performed to detect mucin-5 subtype AC (MUC5AC) on conjunctival cryosections. Cornea and conjunctiva structures were evaluated by light and electron microscopy. Compared with untreated controls, BAC-treated eyes showed significant decreases in Schirmer scores (P = 0.01) and increases in fluorescein scores (P < 0.001) on days 5, 7, and 14. A significant increase in rose bengal scores was noticed as early as day 3 (P = 0.001). Decreases in goblet cell density occurred on days 7 and 14 (P = 0.001). Decreased MUC5AC and histopathologic and ultrastructural disorders of the cornea and conjunctiva were also observed in the BAC group. These findings demonstrated that an ophthalmic preservative, benzalkonium chloride, induced a dry eye syndrome in rabbits with damage to the cornea and conjunctiva, decreased aqueous tear basal secretion, goblet cell loss, and MUC5AC deficiency. This rabbit model was consistent with human dry eye syndrome in both aqueous tear and mucin deficiency and may be appropriate for studying dry eye syndrome.

KINETIC MODEL OF FLUORIDE METABOLISM IN THE RABBIT

EPA Science Inventory

Sodium fluoride, in small doses, was given to rabbits intravenously or by stomach tube, and the appearance of fluoride in the blood and urine was then monitored frequently over the next 10 hours. Compartmental analysis of the data yielded a kinetic model of fluoride metabolism co...

Haziness in X-Ray Paranasal Sinus Water's View in Sinusitis: A Fact or Fiction.

PubMed

Gujrathi, Aatish; Wakode, P T

2013-08-01

It is a clinical dilemma whether patients having no symptoms of sinusitis but sinus haziness in X-ray should be considered as sinusitis or not and patients clinically having sinusitis and do not have radiological evidence should be considered as case of sinusitis or not. This study is an attempt to discuss this issue in details. To study diagnostic efficacy of conventional X-ray para nasal sinus water's view in sinusitis. To study the proportion of asymptomatic individuals showing haziness in conventional X-ray para nasal sinus water's view. Sensitivity and specificity of sinus X-ray in combination (conventional + digital) is 95 and 44%, respectively. Proportion of asymptomatic individuals showing haziness in conventional X-ray and digital X-ray paranasal sinus water's view are 52.4 and 75%, respectively. X-ray paranasal sinus water's view undoubtedly yields valuable information regarding sinus pathology. However it should not be accepted as a diagnosis in itself, but considered in the light of patient's history and clinical findings.

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

Simultaneous quantification of hepatic MRI-PDFF and R2* in a rabbit model with nonalcoholic fatty liver disease.

PubMed

Wang, Xiaomin; Zhang, Xiaojing; Ma, Lin; Li, Shengli

2018-06-20

Quantification of hepatic fat and iron content is important for early detection and monitoring of nonalcoholic fatty liver disease (NAFLD) patients. This study evaluated quantification efficiency of hepatic proton density fat fraction (PDFF) by MRI using NAFLD rabbits. R2* was also measured to investigate whether it correlates with fat levels in NAFLD. NAFLD rabbit model was successfully established by high fat and cholesterol diet. Rabbits underwent MRI examination for fat and iron analyses, compared with liver histological findings. MR examinations were performed on a 3.0T MR system using multi-echo 3D gradient recalled echo (GRE) sequence. MRI-PDFF showed significant differences between different steatosis grades with medians of 3.72% (normal), 5.43% (mild), 9.11% (moderate) and 11.17% (severe), whereas this was not observed in R2*. Close correlation between MRI-PDFF and histological steatosis was observed (r=0.78, P=0.000). Hepatic iron deposit was not found in any rabbits. There was no correlation between R2* and either liver MRI-PDFF or histological steatosis. MR measuring MRI-PDFF and R2* simultaneously provides promising quantification of steatosis and iron. Rabbit NAFLD model confirmed accuracy of MRI-PDFF for liver fat quantification. R2* measurement and relationship between fat and iron of NAFLD liver need further experimental investigation.

Rabbit and Mouse Models of HSV-1 Latency, Reactivation, and Recurrent Eye Diseases

PubMed Central

Webre, Jody M.; Hill, James M.; Nolan, Nicole M.; Clement, Christian; McFerrin, Harris E.; Bhattacharjee, Partha S.; Hsia, Victor; Neumann, Donna M.; Foster, Timothy P.; Lukiw, Walter J.; Thompson, Hilary W.

2012-01-01

The exact mechanisms of HSV-1 establishment, maintenance, latency, reactivation, and also the courses of recurrent ocular infections remain a mystery. Comprehensive understanding of the HSV-1 disease process could lead to prevention of HSV-1 acute infection, reactivation, and more effective treatments of recurrent ocular disease. Animal models have been used for over sixty years to investigate our concepts and hypotheses of HSV-1 diseases. In this paper we present descriptions and examples of rabbit and mouse eye models of HSV-1 latency, reactivation, and recurrent diseases. We summarize studies in animal models of spontaneous and induced HSV-1 reactivation and recurrent disease. Numerous stimuli that induce reactivation in mice and rabbits are described, as well as factors that inhibit viral reactivation from latency. The key features, advantages, and disadvantages of the mouse and rabbit models in relation to the study of ocular HSV-1 are discussed. This paper is pertinent but not intended to be all inclusive. We will give examples of key papers that have reported novel discoveries related to the review topics. PMID:23091352

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

PubMed

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

2017-06-01

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

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.

Enhanced inflammation in New Zealand white rabbits when MERS-CoV reinfection occurs in the absence of neutralizing antibody

PubMed Central

Houser, Katherine V.; Gretebeck, Lisa; Vogel, Leatrice; Sutton, Troy; Orandle, Marlene; Moore, Ian N.

2017-01-01

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic betacoronavirus that was first detected in humans in 2012 as a cause of severe acute respiratory disease. As of July 28, 2017, there have been 2,040 confirmed cases with 712 reported deaths. While many infections have been fatal, there have also been a large number of mild or asymptomatic cases discovered through monitoring and contact tracing. New Zealand white rabbits are a possible model for asymptomatic infection with MERS-CoV. In order to discover more about non-lethal infections and to learn whether a single infection with MERS-CoV would protect against reinfection, we inoculated rabbits with MERS-CoV and monitored the antibody and inflammatory response. Following intranasal infection, rabbits developed a transient dose-dependent pulmonary infection with moderately high levels of viral RNA, viral antigen, and perivascular inflammation in multiple lung lobes that was not associated with clinical signs. The rabbits developed antibodies against viral proteins that lacked neutralizing activity and the animals were not protected from reinfection. In fact, reinfection resulted in enhanced pulmonary inflammation, without an associated increase in viral RNA titers. Interestingly, passive transfer of serum from previously infected rabbits to naïve rabbits was associated with enhanced inflammation upon infection. We further found this inflammation was accompanied by increased recruitment of complement proteins compared to primary infection. However, reinfection elicited neutralizing antibodies that protected rabbits from subsequent viral challenge. Our data from the rabbit model suggests that people exposed to MERS-CoV who fail to develop a neutralizing antibody response, or persons whose neutralizing antibody titers have waned, may be at risk for severe lung disease on re-exposure to MERS-CoV. PMID:28817732

Does platelet-rich plasma have a favorable effect in the early stages of steroid-associated femoral head osteonecrosis in a rabbit model?

PubMed

Karakaplan, Mustafa; Gülabi, Deniz; Topgül, Haldun; Elmalı, Nurzat

2017-08-01

This study aims to investigate the effect of platelet-rich plasma (PRP) on femoral head osteonecrosis and compare it with bone marrow injection and core decompression. A total of 30 healthy, adult, male New Zealand white rabbits (mean weight 2.25±0.15 kg; range 2.0 to 2.5 kg) were used in the study. To create experimental osteonecrosis in all rabbits, 40 mg/kg methylprednisolone acetate was applied intramuscularly. Rabbits were randomly allocated into three groups with 10 rabbits in each: drilling group, PRP group, and bone marrow group. The non-drilled hips of the drilling group were identified as the control group. Rate of necrotic bone was lower in the PRP group compared to other groups. Highest rate of necrotic bone was detected in the control group. New bone formation rate was higher in the PRP group compared to other groups. Lowest new bone formation rate was determined in the control group. Inflammatory reaction rate was higher in the PRP group compared to other groups. Platelet-rich plasma injection may play a positive role in the treatment of steroid-associated osteonecrosis in a rabbit model.

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.

Cardiac Iodine-123-Meta-Iodo-Benzylguanidine Uptake in Carotid Sinus Hypersensitivity.

PubMed

Tan, Maw Pin; Murray, Alan; Hawkins, Terry; Chadwick, Thomas J; Kerr, Simon R J; Parry, Steve W

2015-01-01

Carotid sinus syndrome is the association of carotid sinus hypersensitivity with syncope, unexplained falls and drop attacks in generally older people. We evaluated cardiac sympathetic innervation in this disorder in individuals with carotid sinus syndrome, asymptomatic carotid sinus hypersensitivity and controls without carotid sinus hypersensitivity. Consecutive patients diagnosed with carotid sinus syndrome at a specialist falls and syncope unit were recruited. Asymptomatic carotid sinus hypersensitivity and non-carotid sinus hypersensitivity control participants recruited from a community-dwelling cohort. Cardiac sympathetic innervation was determined using Iodine-123-metaiodobenzylguanidine (123-I-MIBG) scanning. Heart to mediastinal uptake ratio (H:M) were determined for early and late uptake on planar scintigraphy at 20 minutes and 3 hours following intravenous injection of 123-I-MIBG. Forty-two subjects: carotid sinus syndrome (n = 21), asymptomatic carotid sinus hypersensitivity (n = 12) and no carotid sinus hypersensitivity (n = 9) were included. Compared to the non- carotid sinus hypersensitivity control group, the carotid sinus syndrome group had significantly higher early H:M (estimated mean difference, B = 0.40; 95% confidence interval, CI = 0.13 to 0.67, p = 0.005) and late H:M (B = 0.32; 95%CI = 0.03 to 0.62, p = 0.032). There was, however, no significant difference in early H:M (p = 0.326) or late H:M (p = 0.351) between the asymptomatic carotid sinus hypersensitivity group and non- carotid sinus hypersensitivity controls. Cardiac sympathetic neuronal activity is increased relative to age-matched controls in individuals with carotid sinus syndrome but not those with asymptomatic carotid sinus hypersensitivity. Blood pressure and heart rate measurements alone may therefore represent an over simplification in the assessment for carotid sinus syndrome and the relative increase in cardiac sympathetic innervation provides additional clues to understanding the mechanisms behind the symptomatic presentation of carotid sinus hypersensitivity.

A rabbit model of implant-related osteomyelitis inoculated with biofilm after open femoral fracture

PubMed Central

Zhang, Xiang; Ma, Yun-Fei; Wang, Lei; Jiang, Nan; Qin, Cheng-He; Hu, Yan-Jun; Yu, Bin

2017-01-01

Currently, animal models used in research on implant-associated osteomyelitis primarily use intramedullary fixation and initial inoculum of planktonic bacterial cells. However, these techniques have certain limitations, including lack of rotational stability and instable inoculation. To improve these models, the present study aimed to establish a novel rabbit model of implant-associated osteomyelitis using biofilm as the initial inoculum following plate fixation of the femoral fracture. A total of 24 New Zealand White rabbits were randomly divided into two equal groups. Osteotomy was performed at the right femoral shaft using a wire saw following fixation with a 5-hole stainless steel plate. The plates were not colonized with bacteria in group 1, but colonized with a biofilm of Staphylococcus aureus (American Type Culture Collection, 25923) in group 2. All the rabbits were sacrificed after 21 days for clinical, X-ray, micro-computed tomography and histological assessments of the severity of osteomyelitis. Scanning electron microscopy and confocal laser scanning microscopy were used for biofilm assessment. In group 2, pus formation, periosteal reaction, cortical destruction and absorption were observed in all the rabbits and biofilm formation was observed on all the plates. However, no pus formation was observed except for a slight inflammatory response and all the plates appeared clean without infection in group 1. The differences between the two groups were statistically significant regarding histologic scores and semi-quantification of the bacteria on the plates (P<0.001). In the present study, a novel rabbit model of infection following internal plate fixation of open fracture was successfully established, providing a novel tool for the study of implant-associated osteomyelitis. PMID:29201204

A new optical intra-tissue fiber irradiation ALA-PDT in the treatment of acne vulgaris in rabbit model: improved safety and tolerability.

PubMed

Wang, Qian; Jiang, Can; Liu, Wei; Chen, Jin; Lin, Xinyu; Huang, Xiangning; Duan, Xiling

2017-01-01

Photodynamic therapy with topical aminolevulinic acid (ALA-PDT) has been suggested to be effective in treatment of acne vulgaris. However, adverse events occur during and after treatment. To compare the efficacy and tolerability of optical intra-tissue fiber irradiation (OFI) ALA-PDT versus traditional ALA-PDT in treatment of acne vulgaris in rabbit models. Twenty-five rabbits of clean grade were used. Twenty rabbits were randomly selected to establish acne model and the other five were used as control. Rabbits in model group (40 ears) were further divided into four groups (10 ears/group): I, OFI-ALA-PDT with the head of optical fiber inserted into the target lesion (intra-tissue); II, traditional ALA-PDT group; III, OFI group; IV, blank control group without any treatment. Uncomfortable symptoms, adverse events, and effectiveness rates were recorded on post-treatment day 14, 30, and 45. On post-treatment day 14, the effectiveness rate in OFI-ALA-PDT group was obviously higher than that of the other three groups (P<0.05). However, no improved effects were observed in OFI-ALA-PDT group on day 30 and 45. During the period of treatment, the frequencies of uncomfortable symptoms in ALA-PDT group were obviously higher than those in the other three groups (P<0.05). The adverse event rate in OFI-ALA-PDT group was obviously lower than that of the ALA-PDT group (P<0.05). The unblindness of the study and temporary animal models of acne induced may hamper the assessment and monitoring of the results, and future studies are still needed to clarify it further. The OFI-ALA-PDT group (intra-tissue irradiation) showed no improved efficacy on treating rabbit ear acne but had higher safety and better tolerability.

Sinuses / Sinusitis / Rhinosinusitis

MedlinePlus

... Primary Immunodeficiency Disease Related Conditions Drug Guide Conditions Dictionary Just for Kids Library School Tools Videos Virtual ... Search AAAAI Breadcrumb navigation Home ▸ Conditions & Treatments ▸ Conditions Dictionary ▸ Sinuses|Sinusitis|Rhinosinusitis Share | Sinuses | Sinusitis | Rhinosinusitis « Back ...

Critical assessment of the efficiency of CD34 and CD133 antibodies for enrichment of rabbit hematopoietic stem cells.

PubMed

Vašíček, Jaromír; Shehata, Medhat; Schnabl, Susanne; Hilgarth, Martin; Hubmann, Rainer; Jäger, Ulrich; Bauer, Miroslav; Chrenek, Peter

2018-06-08

Rabbits have many hereditary diseases common to humans and are therefore a valuable model for regenerative disease and hematopoietic stem cell (HSC) therapies. Currently, there is no substantial data on the isolation and/or enrichment of rabbit HSCs. This study was initiated to evaluate the efficiency of the commercially available anti-CD34 and anti-CD133 antibodies for the detection and potential enrichment of rabbit HSCs from peripheral blood. PBMCs from rabbit and human blood were labelled with different clones of anti-human CD34 monoclonal antibodies (AC136, 581 and 8G12) and rabbit polyclonal CD34 antibody (pCD34) and anti-human CD133 monoclonal antibodies (AC133 and 293C3). Flow cytometry showed a higher percentage of rabbit CD34 + cells labelled by AC136 in comparison to the clone 581 and pCD34 (P<0.01). A higher percentage of rabbit CD133 + cells were also detected by 293C3 compared to the AC133 clone (P<0.01). Therefore, AC136 clone was used for the indirect immunomagnetic enrichment of rabbit CD34 + cells using magnetic-activated cell sorting (MACS). The enrichment of the rabbit CD34 + cells after sorting was low in comparison to human samples (2.4% vs. 39.6%). PCR analyses confirmed the efficient enrichment of human CD34 + cells and the low expression of CD34 mRNA in rabbit positive fraction. In conclusion, the tested antibodies might be suitable for detection, but not for sorting the rabbit CD34 + HSCs and new specific anti-rabbit CD34 antibodies are needed for efficient enrichment of rabbit HSCs. This article is protected by copyright. All rights reserved. © 2018 American Institute of Chemical Engineers.

[Comparative analysis on data of nasal sinus between helicopter and(strike) fighter pilots under physical examination for change to new-type aircraft].

PubMed

Xu, Xianrong; Ma, Xiaoli; Zhang, Yang; Xiong, Wei

2012-01-01

To comparatively analyze the disease data of nasal sinus between helicopter and (strike) fighter pilots under flying qualification, and then to provide references for aeromedical support as a significant part of new logistics service union in army, The CT data of nasal sinus in 138 pilots who accepted physical examination for change to new-type aircraft, were collected included 46 cases of helicopter pilots and 92 cases of (strike)fighter pilots). The incidence of chronic sinusitis and cyst of nasal sinus were computed respectively in helicopter pilots and (strike)fighter pilots. (1) Fourteen cases suffered from chronic sinusitis (6 cases of maxillary sinusitis, 4 cases of ethmoiditis and 4 cases of maxillary sinusitis and ethmoiditis) in helicopter pilots whose incidence rate of chronic sinusitis was 30.4% (14/46). Of which, 3 cases of antracele were treated. Twelve cases suffered from chronic sinusitis (8 cases of maxillary sinusitis, 1 case of ethmoiditis, 3 cases of maxillary sinusitis and ethmoiditis) in (strike)fighter pilots whose incidence of chronic sinusitis was 13.0% (12/92). Of which, 1 case of antracele was treated. The incidence of chronic sinusitis was higher in helicopter pilots than (strike) fighters pilots (Chi2 = 6.07, P < 0.05). (2) Four cases suffered from unilateral mucosa cysts in maxillary sinus in helicopter pilots whose incidence of cyst of nasal sinus was 8.7% (4/46). Ten cases suffered from mucosa cysts in maxillary sinus (unilateral 8 cases and bilateral 2 cases) in (strike) fighters pilots whose incidence of cyst of nasal sinus was 10.87% (10/92). The difference of the incidence of cyst of nasal sinus was not statistically significant between the helicopter pilots and(strike)fighters pilots. The cysts of nasal sinus did not need treatment in 14 cases of this group data. The incidence of symptomless chronic sinusitis and cyst of nasal sinus are high in pilots. It is related with repeatedly changes of atmosphere pressure during flying. But most chronic sinusitis and cyst of nasal sinus do not need treatment. The incidence of chronic sinusitis is higher in helicopter pilots than(strike)fighter pilots. It may be related with the environment of helicopter which have unclosed cockpit and load other aircrew.

Plain Language Summary: Adult Sinusitis (Sinus Infection).

PubMed

Caspersen, Leslie A; Walter, Lindsey M; Walsh, Sandra A; Rosenfeld, Richard M; Piccirillo, Jay F

2015-08-01

This plain language summary serves as an overview in explaining sinusitis (pronounced sign-you-side-tis). The purpose of this plain language summary is to provide patients with standard language explaining their condition in an easy-to-read format. This summary applies to those 18 years of age or older with sinusitis. The summary is featured as an FAQ (frequently asked question) format. The summary addresses how to manage and treat sinusitis symptoms. Adult sinusitis is often called a sinus infection. A healthcare provider may refer to a sinus infection as rhinosinusitis (pronounced rhi-no-sign-you-side-tis). This includes the nose as well as the sinuses in the name. A sinus infection is the swelling of the sinuses and nasal cavity.The summary is based on the published 2015 "Clinical Practice Guideline: Adult Sinusitis." The evidence-based guideline includes research to support more effective diagnosis and treatment of adult sinus infections. The guideline was developed as a quality improvement opportunity for managing sinus infections by creating clear recommendations to use in medical practice. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

Establishment of a tumor neovascularization animal model with biomaterials in rabbit corneal pouch.

PubMed

Chu, Yu-Ping; Li, Hong-Chuan; Ma, Ling; Xia, Yang

2018-06-01

The present animal model of tumor neovascularization most often used by researchers is zebrafish. For studies on human breast cancer cell neovascularization, a new animal model was established to enable a more convenient study of tumor neovascularization. A sodium alginate-gelatin blend gel system was used to design the new animal model. The model was established using rabbit corneal pouch implantation. Then, the animal model was validated by human breast cancer cell lines MCF-7-Kindlin-2 and MCF-7-CMV. The experiment intuitively observed the relationship between tumor and neovascularization, and demonstrated the advantages of this animal model in the study of tumor neovascularization. The use of sodium alginate-gelatin blends to establish tumor neovascularization in a rabbit corneal pouch is a novel and ideal method for the study of neovascularization. It may be a better animal model for expanding the research in this area. Copyright © 2018 Elsevier Inc. All rights reserved.

Olfactory Training in Improving Sense of Smell After Radiation Therapy in Patients With Paranasal Sinus or Nasopharyngeal Cancer

ClinicalTrials.gov

2017-07-11

Stage 0 Nasopharyngeal Carcinoma; Stage 0 Paranasal Sinus Cancer; Stage I Nasopharyngeal Carcinoma; Stage I Paranasal Sinus Cancer; Stage II Nasopharyngeal Carcinoma; Stage II Paranasal Sinus Cancer; Stage IIA Nasopharyngeal Carcinoma; Stage IIB Nasopharyngeal Carcinoma; Stage III Nasopharyngeal Carcinoma; Stage III Paranasal Sinus Cancer; Stage IV Nasopharyngeal Carcinoma; Stage IV Paranasal Sinus Cancer; Stage IVA Nasopharyngeal Carcinoma; Stage IVA Paranasal Sinus Cancer; Stage IVB Nasopharyngeal Carcinoma; Stage IVB Paranasal Sinus Cancer; Stage IVC Nasopharyngeal Carcinoma; Stage IVC Paranasal Sinus Cancer

[The treatment principles of frontal sinus tract after the frontal approach craniotomy].

PubMed

Yu, Huanxin; Li, Haiyan; Liu, Gang

2015-12-01

To investigate the causes, clinical manifestation and treatment principles of frontal sinus tract after the frontal approach craniotomy. The clinic data of 13 patients with frontal skin sinus tract after the frontal approach craniotomy were retrospectively analyzed. All of them were described in the clinical record to have undergone frontal sinus mucosa pushing down or shaving and bone wax filling in the frontal sinus during the surgery, of whom 3 cases had history of frontal abscess incision drainage. All patients were performed endoscopic frontal sinus surgery and forehead skin sinus tract excision and suture. All of the patients successfully recovered after one-stage operation, and the frontal skin sinus tract was healed. The frontal approach craniotomy with postoperative frontal sinus tract was related with the improper use of bone wax tamponade and sealing of frontal sinus. The treatment principles were to remove bone wax, remove inflammatory granulation tissue around the sinus tract, and to open frontal sinus and promote frontal sinus drainage.

The rabbit blood-shunt model for the study of acute and late sequelae of subarachnoid hemorrhage: technical aspects.

PubMed

Andereggen, Lukas; Neuschmelting, Volker; von Gunten, Michael; Widmer, Hans Rudolf; Takala, Jukka; Jakob, Stephan M; Fandino, Javier; Marbacher, Serge

2014-10-02

Early brain injury and delayed cerebral vasospasm both contribute to unfavorable outcomes after subarachnoid hemorrhage (SAH). Reproducible and controllable animal models that simulate both conditions are presently uncommon. Therefore, new models are needed in order to mimic human pathophysiological conditions resulting from SAH. This report describes the technical nuances of a rabbit blood-shunt SAH model that enables control of intracerebral pressure (ICP). An extracorporeal shunt is placed between the arterial system and the subarachnoid space, which enables examiner-independent SAH in a closed cranium. Step-by-step procedural instructions and necessary equipment are described, as well as technical considerations to produce the model with minimal mortality and morbidity. Important details required for successful surgical creation of this robust, simple and consistent ICP-controlled SAH rabbit model are described.

The microbiology of ethmoid and maxillary sinuses in patients with chronic sinusitis.

PubMed

Aral, Murat; Keles, Erol; Kaygusuz, Irfan

2003-01-01

To investigate aerob-anaerob microorganisms growth in maxillary and ethmoid sinuses by evaluating aspiration materials from patients with chronic sinusitis. The study was performed prospectively, and there were 31 patients (23 men, 8 women; mean age, 31.4+/-14.15, between 18-65 years) who had endoscopic sinus surgery because of chronic sinusitis. During the operation, when the maxillary sinus ostium and ethmoid sinus were opened, readily aspirated materials from sinuses were evaluated regarding aerob and anaerob bacteria. Nose and throat swap samples were collected preoperatively to determine the upper respiratory tract flora and also to understand the relationship between the flora and the microorganisms aspirated from sinuses. Total aerob bacteria count, which was isolated from preoperative nasal swab cultures, was 36, and aerob-anaerob bacteria count that included cultures taken from maxillary and ethmoid sinuses during the functional endoscopic sinus surgery was 42. For each 2 samples, the most common isolated aerob bacteria were coagulase (-) staphylococci. Microorganisms were isolated in 87.0% of 27 patients, in which cultures taken from maxillary and ethmoid sinuses during the functional endoscopic sinus surgery were included. It is determined that the isolated aerob bacteria rate was 90.4%, and the isolated anaerob bacteria rate was 14.2%. All of the 6 samples in which anaerob bacteria isolated were all maxillary sinus aspiration materials. Microorganisms that isolated from the nose and the sinuses were similar with the rate of 25.8%, and microorganisms that isolated from the throat cultures and sinuses were similar with the rate of 22.5%. This study reveals the aerob and anaerob microbiology of the maxillary and ethmoid sinuses so the treatment of chronic sinusitis will be easier.

Effect of corticosteroids on orthodontic tooth movement in a rabbit model.

PubMed

Abtahi, M; Shafaee, H; Saghravania, N; Peel, S; Giddon, D; Sohrabi, K

2014-01-01

While there are a growing number of studies on the effects of medications on orthodontic tooth movement (OTM), only few studies have investigated the role of corticosteroids, despite their widespread use. The aim of the current study was to evaluate the effects of triamcinolone acetonide injection on OTM in a rabbit model. Sixteen one-month old rabbits were randomly divided into two groups: Eight rabbits had triamcinolone acetonide (1 mg/kg/day) administered IM daily for 21 days (test group) while the remaining eight rabbits received no drug (control group). The rabbits in both groups had a tube bonded to the upper central incisors and a stainless steel helical spring was inserted in tube slot to apply 50 cN distal force. After 3 weeks, the rabbits were sacrificed and the distance between mesial corners of incisors was measured The incisors are associated tissue was processed for histology and the apical and cervical area of the roots evaluated. An observer who was blind to the study groups evaluated the specimens. All appliance-treated incisors in test and control groups showed evidence of tooth movement. The distance between the incisors was significantly greater in the triamcinolone acetonide treated group compared to the control group (P < 0.001). Histological examination revealed an increased number of resorption lacunae and decreased number of cuboidal osteoblastic cells around the apical and cervical area of the Incisor roots in the test compared to the control group (P < 0.01). Treatment with triamcinolone acetonide is associated with increased tooth movement in rabbits via increased resorptive activity in the alveolar bone.

Toxicokinetics of perfluorooctane sulfonate in rabbits under environmentally realistic exposure conditions and comparative assessment between mammals and birds.

PubMed

Tarazona, J V; Rodríguez, C; Alonso, E; Sáez, M; González, F; San Andrés, M D; Jiménez, B; San Andrés, M I

2016-01-22

This article describes the toxicokinetics of perfluorooctane sulfonate (PFOS) in rabbits under low repeated dosing, equivalent to 0.085μg/kg per day, and the observed differences between rabbits and chickens. The best fitting for both species was provided by a simple pseudo monocompartmental first-order kinetics model, regulated by two rates, and accounting for real elimination as well as binding of PFOS to non-exchangeable structures. Elimination was more rapid in rabbits, with a pseudo first-order dissipation half-life of 88 days compared to the 230 days observed for chickens. By contrast, the calculated assimilation efficiency for rabbits was almost 1, very close to full absorption, significantly higher than the 0.66 with confidence intervals of 0.64 and 0.68 observed for chickens. The results confirm a very different kinetics than that observed in single-dose experiments confirming clear dose-related differences in apparent elimination rates in rabbits, as previously described for humans and other mammals; suggesting the role of a capacity-limited saturable process resulting in different kinetic behaviours for PFOS in high dose versus environmentally relevant low dose exposure conditions. The model calculations confirmed that the measured maximum concentrations were still far from the steady state situation, and that the different kinetics between birds and mammals should may play a significant role in the biomagnifications assessment and potential exposure for humans and predators. For the same dose regime, the steady state concentration was estimated at about 36μg PFOS/L serum for rabbits, slightly above one-half of the 65μg PFOS/L serum estimated for chickens. The toxicokinetic parameters presented here can be used for higher-tier bioaccumulation estimations of PFOS in rabbits and chickens as starting point for human health exposure assessments and as surrogate values for modeling PFOS kinetics in wild mammals and bird in exposure assessment of predatory species. Published by Elsevier Ireland Ltd.

Sealing Penetrating Eye Injuries Using Photoactivated Bonding

DTIC Science & Technology

2014-10-01

treatment parameters that produce strong, immediate water- tight sealing of penetrating cornea and scleral wounds using rabbit eye models. The seal...conventional, bare fiber system using ex vivo rabbit eyes and the standard treatment protocol (Appendix 1). The bonding strength produced by two...wounds in rabbit eyes . Initial studies demonstrated that thermal damage to the iris are not a concern during the 7 treatment . A prototype light delivery

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

PubMed

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

2016-01-01

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

Characterization of chronic vocal fold scarring in a rabbit model.

PubMed

Rousseau, Bernard; Hirano, Shigeru; Chan, Roger W; Welham, Nathan V; Thibeault, Susan L; Ford, Charles N; Bless, Diane M

2004-03-01

The purpose of the current study was to assess the histologic and rheologic properties of the scarred vocal fold lamina propria during a chronic phase of wound repair in a rabbit model. Eighteen rabbit larynges were scarred using a procedure that involved stripping the vocal fold lamina propria down to the thyroarytenoid muscle, using 3-mm microforceps. The approximate dimension of injury to the vocal fold was 3 x 1.5 x 0.5 mm [length x width x depth]. At 6 months postoperatively, histologic analysis of the scarred and control lamina propria in eight of these rabbits was completed for collagen, procollagen, elastin, and hyaluronic acid. Compared with control samples, scarred tissue samples revealed fragmented and disorganized elastin fibers. Additionally, collagen was significantly increased, organized, and formed thick bundles in the scarred vocal fold lamina propria. Measurements of the viscoelastic shear properties of the scarred and control lamina propria in the remaining 10 rabbits revealed increased elastic shear modulus (G') in 8 of 10 scarred samples and increased dynamic viscosity (eta') in 9 of 10 scarred samples. Although rheologic differences were not statistically significant, they revealed that on average, scarred samples were stiffer and more viscous than the normal controls. Histologic data are interpreted as indicating that by 6 months postinjury, the scarred rabbit vocal fold has reached a mature phase of wound repair, characterized by an increased, organized, and thick bundle collagen matrix. Rheologic data are interpreted as providing support for the potential role of increased, thick bundle collagen, and a disorganized elastin network on shear stiffness and dynamic viscosity in the chronic vocal fold scar. Based on these results, a 6-month postoperative time frame is proposed for future studies of chronic vocal fold scarring using the rabbit animal model.

The rabbit as an infection model for equine proliferative enteropathy

PubMed Central

Sampieri, Francesca; Allen, Andrew L.; Pusterla, Nicola; Vannucci, Fabio A.; Antonopoulos, Aphroditi J.; Ball, Katherine R.; Thompson, Julie; Dowling, Patricia M.; Hamilton, Don L.; Gebhart, Connie J.

2013-01-01

The objective of this study was to demonstrate the susceptibility of rabbits to Lawsonia intracellularis obtained from a case of clinical equine proliferative enteropathy (EPE). This is a preliminary step toward developing a rabbit infection model for studying pathogenesis and therapy of EPE in horses. Nine does were equally assigned to 3 groups. Animals in 2 groups (Group 1 and Group 2) were orally inoculated with different doses of cell-cultured L. intracellularis. Controls (Group 3) were sham-inoculated. Feces and blood were collected before the rabbits were infected and at 7, 14, and 21 days post-infection (DPI). Serum immunoglobulin G (IgG) titers were measured using an immunoperoxidase monolayer assay (IPMA) and fecal samples were analyzed with quantitative polymerase chain reaction (qPCR). A doe from each group was euthanized at 7, 14, and 21 DPI for collection and evaluation of intestinal samples. Tissues were stained by routine hematoxylin and eosin (H&E) method and immunohistochemistry (IHC) with L. intracellularis-specific mouse monoclonal antibody. At 14 DPI, serologic responses were detected in both infected groups, which maintained high titers through to 21 DPI. Lawsonia intracellularis DNA was detected in the feces of Group 2 on 7 DPI and in both infected groups on 14 DPI. Gross lesions were apparent in Group 1 and Group 2 on 14 DPI. Immunohistochemistry confirmed L. intracellularis antigen within cells of rabbits in Group 1 and Group 2 on 7, 14, and 21 DPI. No lesions, serologic response, shedding, or IHC labeling were found in Group 3 rabbits. This study describes an EPE rabbit model that simulates natural infection, as typical lesions, immune response, and fecal shedding were present. PMID:24082402

Sigmoid Sinus Diverticulum, Dehiscence, and Venous Sinus Stenosis: Potential Causes of Pulsatile Tinnitus in Patients with Idiopathic Intracranial Hypertension?

PubMed

Lansley, J A; Tucker, W; Eriksen, M R; Riordan-Eva, P; Connor, S E J

2017-09-01

Pulsatile tinnitus is experienced by most patients with idiopathic intracranial hypertension. The pathophysiology remains uncertain; however, transverse sinus stenosis and sigmoid sinus diverticulum/dehiscence have been proposed as potential etiologies. We aimed to determine whether the prevalence of transverse sinus stenosis and sigmoid sinus diverticulum/dehiscence was increased in patients with idiopathic intracranial hypertension and pulsatile tinnitus relative to those without pulsatile tinnitus and a control group. CT vascular studies of patients with idiopathic intracranial hypertension with pulsatile tinnitus ( n = 42), without pulsatile tinnitus ( n = 37), and controls ( n = 75) were independently reviewed for the presence of severe transverse sinus stenosis and sigmoid sinus diverticulum/dehiscence according to published criteria. The prevalence of transverse sinus stenosis and sigmoid sinus diverticulum/dehiscence in patients with idiopathic intracranial hypertension with pulsatile tinnitus was compared with that in the nonpulsatile tinnitus idiopathic intracranial hypertension group and the control group. Further comparisons included differing degrees of transverse sinus stenosis (50% and 75%), laterality of transverse sinus stenosis/sigmoid sinus diverticulum/dehiscence, and ipsilateral transverse sinus stenosis combined with sigmoid sinus diverticulum/dehiscence. Severe bilateral transverse sinus stenoses were more frequent in patients with idiopathic intracranial hypertension than in controls ( P < .001), but there was no significant association between transverse sinus stenosis and pulsatile tinnitus within the idiopathic intracranial hypertension group. Sigmoid sinus dehiscence (right- or left-sided) was also more common in patients with idiopathic intracranial hypertension compared with controls ( P = .01), but there was no significant association with pulsatile tinnitus within the idiopathic intracranial hypertension group. While our data corroborate previous studies demonstrating increased prevalence of sigmoid sinus diverticulum/dehiscence and transverse sinus stenosis in idiopathic intracranial hypertension, we did not establish an increased prevalence in patients with idiopathic intracranial hypertension with pulsatile tinnitus compared with those without. It is therefore unlikely that these entities represent a direct structural correlate of pulsatile tinnitus in patients with idiopathic intracranial hypertension. © 2017 by American Journal of Neuroradiology.

Cardiac Iodine-123-Meta-Iodo-Benzylguanidine Uptake in Carotid Sinus Hypersensitivity

PubMed Central

Tan, Maw Pin; Murray, Alan; Hawkins, Terry; Chadwick, Thomas J.; Kerr, Simon R. J.; Parry, Steve W.

2015-01-01

Background Carotid sinus syndrome is the association of carotid sinus hypersensitivity with syncope, unexplained falls and drop attacks in generally older people. We evaluated cardiac sympathetic innervation in this disorder in individuals with carotid sinus syndrome, asymptomatic carotid sinus hypersensitivity and controls without carotid sinus hypersensitivity. Methods Consecutive patients diagnosed with carotid sinus syndrome at a specialist falls and syncope unit were recruited. Asymptomatic carotid sinus hypersensitivity and non-carotid sinus hypersensitivity control participants recruited from a community-dwelling cohort. Cardiac sympathetic innervation was determined using Iodine-123-metaiodobenzylguanidine (123-I-MIBG) scanning. Heart to mediastinal uptake ratio (H:M) were determined for early and late uptake on planar scintigraphy at 20 minutes and 3 hours following intravenous injection of 123-I-MIBG. Results Forty-two subjects: carotid sinus syndrome (n = 21), asymptomatic carotid sinus hypersensitivity (n = 12) and no carotid sinus hypersensitivity (n = 9) were included. Compared to the non- carotid sinus hypersensitivity control group, the carotid sinus syndrome group had significantly higher early H:M (estimated mean difference, B = 0.40; 95% confidence interval, CI = 0.13 to 0.67, p = 0.005) and late H:M (B = 0.32; 95%CI = 0.03 to 0.62, p = 0.032). There was, however, no significant difference in early H:M (p = 0.326) or late H:M (p = 0.351) between the asymptomatic carotid sinus hypersensitivity group and non- carotid sinus hypersensitivity controls. Conclusions Cardiac sympathetic neuronal activity is increased relative to age-matched controls in individuals with carotid sinus syndrome but not those with asymptomatic carotid sinus hypersensitivity. Blood pressure and heart rate measurements alone may therefore represent an over simplification in the assessment for carotid sinus syndrome and the relative increase in cardiac sympathetic innervation provides additional clues to understanding the mechanisms behind the symptomatic presentation of carotid sinus hypersensitivity. PMID:26057525

Validation of serum IGF-I as a biomarker to monitor the bioactivity of exogenous growth hormone agonists and antagonists in rabbits

PubMed Central

Bielohuby, Maximilian; Zarkesh-Esfahani, Sayyed Hamid; Manolopoulou, Jenny; Wirthgen, Elisa; Walpurgis, Katja; Toghiany Khorasgani, Mohaddeseh; Aghili, Zahra Sadat; Wilkinson, Ian Robert; Hoeflich, Andreas; Thevis, Mario; Ross, Richard J.; Bidlingmaier, Martin

2014-01-01

The development of new growth hormone (GH) agonists and growth hormone antagonists (GHAs) requires animal models for pre-clinical testing. Ideally, the effects of treatment are monitored using the same pharmacodynamic marker that is later used in clinical practice. However, intact rodents are of limited value for this purpose because serum IGF-I, the most sensitive pharmacodynamic marker for the action of GH in humans, shows no response to treatment with recombinant human GH and there is little evidence for the effects of GHAs, except when administered at very high doses or when overexpressed. As an alternative, more suitable model, we explored pharmacodynamic markers of GH action in intact rabbits. We performed the first validation of an IGF-I assay for the analysis of rabbit serum and tested precision, sensitivity, linearity and recovery using an automated human IGF-I assay (IDS-iSYS). Furthermore, IGF-I was measured in rabbits of different strains, age groups and sexes, and we monitored IGF-I response to treatment with recombinant human GH or the GHA Pegvisomant. For a subset of samples, we used LC-MS/MS to measure IGF-I, and quantitative western ligand blot to analyze IGF-binding proteins (IGFBPs). Although recovery of recombinant rabbit IGF-I was only 50% in the human IGF-I assay, our results show that the sensitivity, precision (1.7–3.3% coefficient of variation) and linearity (90.4–105.6%) were excellent in rabbit samples. As expected, sex, age and genetic background were major determinants of IGF-I concentration in rabbits. IGF-I and IGFBP-2 levels increased after single and multiple injections of recombinant human GH (IGF-I: 286±22 versus 434±26 ng/ml; P<0.01) and were highly correlated (P<0.0001). Treatment with the GHA lowered IGF-I levels from the fourth injection onwards (P<0.01). In summary, we demonstrated that the IDS-iSYS IGF-I immunoassay can be used in rabbits. Similar to rodents, rabbits display variations in IGF-I depending on sex, age and genetic background. Unlike in rodents, the IGF-I response to treatment with recombinant human GH or a GHA closely mimics the pharmacodynamics seen in humans, suggesting that rabbits are a suitable new model to test human GH agonists and antagonists. PMID:25239917

Rabbit ventricular myocardium undergoing simulated ischemia and reperfusion in a double compartment tissue bath: a model to investigate both antiarrhythmic and arrhythmogenic likelihood.

PubMed

Alexandre, Joachim; Schiariti, Michele; Rouet, René; Puddu, Paolo Emilio

2013-01-01

An ischemia/reperfusion-simulating model in rabbit tissue should be right oriented and clinically relevant to provide a non expensive approach for manipulations of currents involved in the repolarization process. Standard right ventricular guinea-pig (N=18) and newly investigated rabbit (N=12) myocardial strips were placed in a special perfusion chamber allowing partition into two segments independently superfused with oxygenated Tyrode's solution or a modified Tyrode's solution mimicking ischemia by: 1) increased extracellular potassium concentration (12 mmol/L), 2) decreased HCO3 (-) concentration (9 mmol/L), leading to a decrease in pH (6.90 ± 0.05), 3) decreased pO2 by replacement of 95% O2 and 5% CO2 by 95% N2 and 5% CO2 gas mixture, and 4) complete withdrawal of glucose. There were significant differences in rabbit as compared to guinea-pig preparations in baseline (p<0.02) and post-ischemic-like (p<0.01) APA and RMP with lower values in the formers, and lower post-ischemic Vmax in rabbit preparations (25±15 versus 97±83 V/s, p<0.01) but neither baseline nor post-ischemic-like or absolute changes in APD50, APD90 were different. In ischemia- and reperfusion-like phases, there were high proportions of single spontaneous repetitive responses, both in guinea-pig (respectively 50 and 89%) and rabbit preparations (respectively 67 and 92%). Guinea-pig preparations showed higher incidence of severe spontaneous repetitive responses (61 versus 17%, p<0.02). This rabbit model is proposed to investigate both anti- and pro-arrhythmic effects of drugs acting at various levels electrophysiologically, which may be obtained with great power and relatively few (around 10 per group) preparations. This model should now be tested pharmacologically.

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

PubMed

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

2010-02-10

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

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

USE OF REPEATED BRONCHOALVEOLAR LAVAGE IN RABBITS TO ASSESS POLLUTANT-INDUCED LUNG CHANGES IN AN ANIMAL MODEL OF CARDIOVASCULAR (CV) DISEASE.

EPA Science Inventory

Animal models of coronary heart disease (e.g., hyperlipidemic rabbits) are being used to investigate epidemiologic associations between higher levels of air pollution and adverse CV consequences. Mechanisms by which pollutant-induced lung or systemic inflammation leads to acute C...

Co‐occurrence dynamics of endangered Lower Keys marsh rabbits and free‐ranging domestic cats: Prey responses to an exotic predator removal program

USGS Publications Warehouse

Cove, Michael V.; Gardner, Beth; Simons, Theodore R.; O'Connell, Allan F.

2018-01-01

The Lower Keys marsh rabbit (Sylvilagus palustris hefneri) is one of many endangered endemic species of the Florida Keys. The main threats are habitat loss and fragmentation from sea‐level rise, development, and habitat succession. Exotic predators such as free‐ranging domestic cats (Felis catus) pose an additional threat to these endangered small mammals. Management strategies have focused on habitat restoration and exotic predator control. However, the effectiveness of predator removal and the effects of anthropogenic habitat modifications and restoration have not been evaluated. Between 2013 and 2015, we used camera traps to survey marsh rabbits and free‐ranging cats at 84 sites in the National Key Deer Refuge, Big Pine Key, Florida, USA. We used dynamic occupancy models to determine factors associated with marsh rabbit occurrence, colonization, extinction, and the co‐occurrence of marsh rabbits and cats during a period of predator removal. Rabbit occurrence was positively related to freshwater habitat and patch size, but was negatively related to the number of individual cats detected at each site. Furthermore, marsh rabbit colonization was negatively associated with relative increases in the number of individual cats at each site between survey years. Cat occurrence was negatively associated with increasing distance from human developments. The probability of cat site extinction was positively related to a 2‐year trapping effort, indicating that predator removal reduced the cat population. Dynamic co‐occurrence models suggested that cats and marsh rabbits co‐occur less frequently than expected under random conditions, whereas co‐detections were site and survey‐specific. Rabbit site extinction and colonization were not strongly conditional on cat presence, but corresponded with a negative association. Our results suggest that while rabbits can colonize and persist at sites where cats occur, it is the number of individual cats at a site that more strongly influences rabbit occupancy and colonization. These findings indicate that continued predator management would likely benefit endangered small mammals as they recolonize restored habitats.

Sclera-Choroid-RPE Transport of Eight β-Blockers in Human, Bovine, Porcine, Rabbit, and Rat Models

PubMed Central

Kadam, Rajendra S.; Cheruvu, Narayan P. S.; Edelhauser, Henry F.

2011-01-01

Purpose. To determine the influence of drug lipophilicity, ocular pigmentation, and species differences on transscleral solute transport. Methods. The transport of eight β-blockers across excised sclera/sclera-choroid-RPE (SCRPE) of albino rabbit, pigmented rabbit, human, porcine, and bovine eyes was determined over 6 hours. The ex vivo transscleral β-blocker transport to the vitreous at the end of 6 hours was determined in euthanatized, pigmented Brown Norway rats. The thicknesses of the sclera and SCRPE and the melanin content in choroid-RPE (CRPE) were measured to determine whether species differences in drug transport can be explained on this basis. Results. Solute lipophilicity inversely correlated with the SCRPE cumulative percentage of transport in all species (R2 ≥ 0.80). The CRPE impeded the SCRPE transport of all β-blockers (51%–64% resistance in the rabbits; 84%–99.8% in the bovine and porcine eyes) more than the sclera, with the impedance increasing with lipophilicity. SCRPE transport followed the trend albino rabbit > pigmented rabbit > human > porcine > bovine, and a cross-species comparison showed good Spearman's rho correlation (R2 ≥ 0.85). Bovine (R2 = 0.84), porcine (R2 = 0.84), and human (R2 = 0.71) SCRPE transport was more predictive than that in the rabbit models (R2 = 0.60–0.61) of transscleral solute transport to the vitreous in rats. The CRPE concentrations were higher in pigmented rabbits than in albino rabbits. The melanin content of the CRPE exhibited the trend albino rabbit ≪ pigmented rabbit < porcine ∼ bovine < rat. Normalization to scleral thickness abolished the species differences in scleral transport. Normalization to SCRPE thickness and melanin content significantly reduced species differences in SCRPE transport. Conclusions. Owing to the presence of pigment and drug binding, choroid-RPE is the principal barrier to transscleral β-blocker transport, with the barrier being more significant for lipophilic β-blockers. Although different in magnitude between species, sclera/SCRPE transport can be correlated between species. Tissue thickness accounts for the species differences in scleral transport. Differences in tissue thickness and melanin content largely account for the species differences in SCRPE transport. PMID:21282583

[Causes and management of frontal sinusitis after transfrontal craniotomy].

PubMed

Liu, T C; Yu, X F; Gu, Z W; Bai, W L; Wang, Z H; Cao, Z W

2018-02-01

Objective: The aim of this study is to investigate the causes and the strategy of frontal sinusitis after transfrontal craniotomy by endoscopic frontal sinus surgery and traditional surgery with facial incision. Method: A total of thirty-four patients with frontal sinusitis after transfrontal craniotomy were admitted, with the symptom of purulence stuff, headache and upper eyelid discharging. The onset time was 2.6 years on average. The frontal sinus CT and MRI images showed frontal sinusitis. Twenty-seven patients were treated with endoscopic frontal sinus surgery, and seven patient was treated with combined endoscopic and traditional frontal sinus surgery. In the revision surgery, the bone wax and inflammatory granulation tissue were cleaned out in both operational methods. The cure standard was that the postoperative frontal sinus inflammation disappeared and the drainage of the volume recess was unobstructed. Result: Thirty-four patients had a history of transfrontal craniotomy, and there was a record of bone wax packing in every operation. Among twenty-seven patients with endoscopic frontal sinus surgery, Twenty-five cases cured and two cases were operated twice. Seven patients were cured with combined endoscopic and traditional frontal sinus surgery. Conclusion: The frontal sinusitis after transfrontal craniotomy may be related to the inadequate sinus management, especially bone wax to be addressed to the frontal sinus ramming leading to frontal sinus mucosa secretion obstruction and poor drainage. Endoscopic frontal sinus surgery is a way of minimally invasive surgery. The satisfying curative effect can be obtained by endoscopic removal of bone wax, inflammatory granulation tissue, and the enlargement of frontal sinus aperture after exposure to the frontal sinus, and some cases was treated with both operation method.

Gelatin microspheres containing calcitonin gene-related peptide or substance P repair bone defects in osteoporotic rabbits.

PubMed

Chen, Jianghao; Liu, Wei; Zhao, Jinxiu; Sun, Cong; Chen, Jie; Hu, Kaijin; Zhang, Linlin; Ding, Yuxiang

2017-03-01

To investigate the therapeutic effect of gelatin microspheres containing different concentrations of calcitonin gene-related peptide (CGRP) or substance P on repairing bone defects in a rabbit osteoporosis model. Gelatin microspheres containing different concentrations of CGRP or substance P promoted osteogenesis after 3 months in a rabbit osteoporotic bone defective model. From micro-computed tomography imaging results, 10 nM CGRP was optimal for increasing the trabecular number and decreasing the trabecular bone separation degree; similar effects were observed with the microspheres containing 1 µM substance P. Histological analysis showed that the gelatin microspheres containing CGRP or substance P, regardless of the concentration, effectively promoted osteogenesis, and the highest effect was achieved in the groups containing 1 µM CGRP or 1 µM substance P. Gelatin microspheres containing CGRP or substance P effectively promoted osteogenesis in a rabbit osteoporotic bone defect model dose-dependently, though their effects in repairing human alveolar ridge defects still need further investigation.

Wave of chaos in a spatial eco-epidemiological system: Generating realistic patterns of patchiness in rabbit-lynx dynamics.

PubMed

Upadhyay, Ranjit Kumar; Roy, Parimita; Venkataraman, C; Madzvamuse, A

2016-11-01

In the present paper, we propose and analyze an eco-epidemiological model with diffusion to study the dynamics of rabbit populations which are consumed by lynx populations. Existence, boundedness, stability and bifurcation analyses of solutions for the proposed rabbit-lynx model are performed. Results show that in the presence of diffusion the model has the potential of exhibiting Turing instability. Numerical results (finite difference and finite element methods) reveal the existence of the wave of chaos and this appears to be a dominant mode of disease dispersal. We also show the mechanism of spatiotemporal pattern formation resulting from the Hopf bifurcation analysis, which can be a potential candidate for understanding the complex spatiotemporal dynamics of eco-epidemiological systems. Implications of the asymptotic transmission rate on disease eradication among rabbit population which in turn enhances the survival of Iberian lynx are discussed. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

[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.

Naringin administration inhibits platelet aggregation and release by reducing blood cholesterol levels and the cytosolic free calcium concentration in hyperlipidemic rabbits

PubMed Central

XIAO, YANG; LI, LAI-LAI; WANG, YAN-YAN; GUO, JING-JING; XU, WEN-PING; WANG, YAN-YAN; WANG, YI

2014-01-01

This study investigated the effects of naringin on platelet aggregation and release in hyperlipidemic rabbits, and the underlying mechanisms. The safety of naringin was also investigated. The rabbits were orally administered 60, 30 or 15 mg/kg of naringin once a day for 14 days after being fed a high fat/cholesterol diet for four weeks. Following the two weeks of drug administration, the degree of platelet aggregation induced by arachidonic acid, adenosine diphosphate and collagen was significantly reduced by naringin at certain doses compared with those in the rabbits of the model group (P<0.01). The levels of P-selectin and platelet factor 4 (PF4) also decreased following treatment with naringin compared with those of the model group. Certain doses of naringin significantly reduced the total cholesterol (TC) levels and elevated the ratio of high-density lipoprotein cholesterol to TC compared with those in the model group, and significantly decreased the cytosolic free calcium concentration ([Ca2+]i). No significant difference in the coagulation function was observed between the control and drug-treatment groups. These results indicate that naringin improved platelet aggregation and inhibited the excessive release of P-selectin and PF4 in hyperlipidemic rabbits. This study suggests that the antiplatelet effect of naringin may be due to its ability to regulate the levels of blood cholesterol and [Ca2+]i in platelets. Naringin also did not cause bleeding in the hyperlipidemic rabbits. PMID:25120631

Rabbit Trochlear Model of Osteochondral Allograft Transplantation

PubMed Central

To, Nhat; Curtiss, Shane; Neu, Corey P; Salgado, Christopher J; Jamali, Amir A

2011-01-01

Allografting and autografting of osteochondral tissues is a promising strategy to treat articular cartilage lesions in damaged joints. We developed a new model of fresh osteochondral allografting using the entire rabbit trochlea. The objective of the current study was to demonstrate that this model would achieve reproducible graft–host healing and maintain normal articular cartilage histologic, immunolocalization, and biochemical characteristics after transplantation under diverse storage and transplantation conditions. New Zealand white (n = 8) and Dutch belted (n = 8) rabbits underwent a 2-stage transplantation operation using osteochondral grafts that had been stored for 2 or 4 wk. Trochlear grafts harvested from the left knee were transplanted to the right knee as either autografts or allografts. Grafts were fixed with 22-gauge steel wire or 3-0 nylon suture. Rabbits were euthanized for evaluation at 1, 2, 4, 6, and 12 wk after transplantation. All grafts that remained in vivo for at least 4 wk demonstrated 100% interface healing by microCT. Trabecular bridging was present at the host–graft interface starting at 2 wk after transplantation, with no significant difference in cartilage histology between the various groups. The combined histology scores indicated minimal evidence of osteoarthritis. Immunostaining revealed that superficial zone protein was localized at the surface of all transplants. The rabbit trochlear model met our criteria for a successful model in regard to the ease of the procedure, low rate of surgical complications, relatively large articular cartilage surface area, and amount of host–graft bone interface available for analysis. PMID:22330350

MRI and hybrid PET/CT for monitoring tumour metastasis in a metastatic breast cancer model in rabbit.

PubMed

Wang, Ling; Yao, Qing; Wang, Jing; Wei, Guangquan; Li, Guoquan; Li, Dong; Ling, Rui; Chen, Jianghao

2008-02-01

To study tumour growth and metastasis in a rabbit metastatic breast cancer (MBC) model and find the most sensitive screening modality in monitoring tumour metastasis. The MBC model was established by injecting a VX2 tumour mass suspension into the mammary glands of 23 rabbits and was monitored by using physical examination, X-ray, MRI and hybrid PET/CT. Of all 23 rabbits, axillary lymph node metastasis was detected in 21 (91%) at day 33 after tumour inoculation, mediastinal node metastasis in five (22%) at day 42, abdominal node metastasis in two (9%) at day 48, lung metastasis in six (26%) at day 39, liver metastasis in three (13%) at day 48, and lumbar spine metastasis in one (4%) at day 51. Tumour invasion of pleura was found in one, stomach wall in one, and pleura and stomach concurrently in one rabbit. Sensitivity for detection of lymph node metastases was 78.6% (22/28) and 67.9% (19/28) with MRI and PET/CT, respectively; and sensitivity for detection of metastases in distant organs was 85.7% (12/14) and 71.4% (10/14), respectively. The MBC model used here exhibits fast tumour growth and extensive metastasis in a relatively short period. Its metastatic pattern is quite similar to that of human MBC and hence could be potentially used as a model for testing imaging modalities and translational research, e.g., MBC management. MRI is superior to PET/CT in monitoring tumour metastasis.

Protective effects of molecular hydrogen on steroid-induced osteonecrosis in rabbits via reducing oxidative stress and apoptosis.

PubMed

Li, Jia; Ge, Zhaogang; Fan, Lihong; Wang, Kunzheng

2017-02-02

The objective of this study was to investigate the protective effects of molecular hydrogen, a novel and selective antioxidant, on steroid-induced osteonecrosis (ON) in a rabbit model. Sixty rabbits were randomly divided into two groups (model group and hydrogen group). Osteonecrosis was induced according to an established protocol of steroid-induced ON. Rabbits in the hydrogen group were treated with intraperitoneal injections of molecular hydrogen at 10 ml/kg body weight for seven consecutive days. Plasma levels of total cholesterol, triglycerides, soluble thrombomodulin(sTM), glutathione(GSH) and malondialdehyde(MDA) were measured before and after steroid administration. The presence or absence of ON was examined histopathologically. Oxidative injury and vascular injury were assessed in vivo by immunohistochemical staining of 8-hydoxy-2-deoxyguanosine(8-OHdG) and MDA, and ink artery infusion angiography. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assays were performed to measure apoptosis. The incidence of steroid-induced ON was significantly lower in hydrogen group (28.6%) than that in model group (68.0%). No statistically differences were observed on the levels of total cholesterol and triglycerides. Oxidative injury, vascular injury and apoptosis were attenuated in the hydrogen group compared with those in the model group in vivo. These results suggested that molecular hydrogen prevents steroid-induced osteonecrosis in rabbits by suppressing oxidative injury, vascular injury and apoptosis.

Progressive Vascular Functional and Structural Damage in a Bronchopulmonary Dysplasia Model in Preterm Rabbits Exposed to Hyperoxia.

PubMed

Jiménez, Julio; Richter, Jute; Nagatomo, Taro; Salaets, Thomas; Quarck, Rozenn; Wagennar, Allard; Wang, Hongmei; Vanoirbeek, Jeroen; Deprest, Jan; Toelen, Jaan

2016-10-24

Bronchopulmonary dysplasia (BPD) is caused by preterm neonatal lung injury and results in oxygen dependency and pulmonary hypertension. Current clinical management fails to reduce the incidence of BPD, which calls for novel therapies. Fetal rabbits have a lung development that mimics humans and can be used as a translational model to test novel treatment options. In preterm rabbits, exposure to hyperoxia leads to parenchymal changes, yet vascular damage has not been studied in this model. In this study we document the early functional and structural changes of the lung vasculature in preterm rabbits that are induced by hyperoxia after birth. Pulmonary artery Doppler measurements, micro-CT barium angiograms and media thickness of peripheral pulmonary arteries were affected after seven days of hyperoxia when compared to controls. The parenchyma was also affected both at the functional and structural level. Lung function testing showed higher tissue resistance and elastance, with a decreased lung compliance and lung capacity. Histologically hyperoxia leads to fewer and larger alveoli with thicker walls, less developed distal airways and more inflammation than normoxia. In conclusion, we show that the rabbit model develops pulmonary hypertension and developmental lung arrest after preterm lung injury, which parallel the early changes in human BPD. Thus it enables the testing of pharmaceutical agents that target the cardiovascular compartment of the lung for further translation towards the clinic.

Progressive Vascular Functional and Structural Damage in a Bronchopulmonary Dysplasia Model in Preterm Rabbits Exposed to Hyperoxia

PubMed Central

Jiménez, Julio; Richter, Jute; Nagatomo, Taro; Salaets, Thomas; Quarck, Rozenn; Wagennar, Allard; Wang, Hongmei; Vanoirbeek, Jeroen; Deprest, Jan; Toelen, Jaan

2016-01-01

Bronchopulmonary dysplasia (BPD) is caused by preterm neonatal lung injury and results in oxygen dependency and pulmonary hypertension. Current clinical management fails to reduce the incidence of BPD, which calls for novel therapies. Fetal rabbits have a lung development that mimics humans and can be used as a translational model to test novel treatment options. In preterm rabbits, exposure to hyperoxia leads to parenchymal changes, yet vascular damage has not been studied in this model. In this study we document the early functional and structural changes of the lung vasculature in preterm rabbits that are induced by hyperoxia after birth. Pulmonary artery Doppler measurements, micro-CT barium angiograms and media thickness of peripheral pulmonary arteries were affected after seven days of hyperoxia when compared to controls. The parenchyma was also affected both at the functional and structural level. Lung function testing showed higher tissue resistance and elastance, with a decreased lung compliance and lung capacity. Histologically hyperoxia leads to fewer and larger alveoli with thicker walls, less developed distal airways and more inflammation than normoxia. In conclusion, we show that the rabbit model develops pulmonary hypertension and developmental lung arrest after preterm lung injury, which parallel the early changes in human BPD. Thus it enables the testing of pharmaceutical agents that target the cardiovascular compartment of the lung for further translation towards the clinic. PMID:27783043

Sinus Floor Augmentation Using Straumann® BoneCeramic™ and Bio-Oss® in a Split Mouth Design and Later Placement of Implants: A 5-Year Report from a Longitudinal Study.

PubMed

Mordenfeld, Arne; Lindgren, Christer; Hallman, Mats

2016-10-01

Straumann® BoneCeramic™ is a synthetic biphasic calcium phosphate (BCP) aimed for sinus floor augmentation. Long-term follow-up of implants placed in BCP after sinus augmentation is still missing. The primary aim of the study was to compare survival rates and marginal bone loss of Straumann SLActive implants placed in either BCP (test) or Bio-Oss® (DBB) (control) after sinus floor augmentation. The secondary aim was to calculate graft sinus height at different time points. Bilateral sinus floor augmentation was performed in a split mouth model. Eleven patients (mean age 67 years) received 100% BCP on one side and 100% DBB on the contralateral side. After 8 months of graft healing, 62 Straumann SLActive implants were placed. After 5 years of functional loading (6 years after augmentation) of implants, marginal bone levels and grafted sinus height were measured, and implant survival and success rates were calculated. After 5 years of loading, all prosthetic constructions were in function although two implants were lost in each grafting material. The overall implant survival rate was 93.5% (91.7% for BCP, 91.3% for DBB, and 100% for residual bone). The success rates were 83.3% and 91.3% for BCP and DBB, respectively. There was no statistically significant difference in mean marginal bone level after 5 years between BCP (1.4 ± 1.2 mm) and DBB (1.0 ± 0.7 mm). Graft height reduction (GHR) after 6 years was limited to 6.6% for BCP and 5.8% for DBB. In this limited RCT study, the choice of biomaterial used for sinus floor augmentation did not seem to have any impact on survival rates and marginal bone level of the placed implants after 5 years of functional loading and GHR was minimal. © 2015 Wiley Periodicals, Inc.

Rabbits killing birds revisited.

PubMed

Zhang, Jimin; Fan, Meng; Kuang, Yang

2006-09-01

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

Evaluation of antiviral efficacy of Chinese traditional medicine Babao Dan in rabbits infected with hepatitis E virus.

PubMed

Gong, Wanyun; Liu, Lin; Li, Manyu; Wang, Lin; Zhang, Mingyu; Luo, Zhengxin; Sridhar, Siddharth; Woo, Patrick C Y; Wang, Ling

2018-06-20

Hepatitis E virus (HEV) is a major cause of acute viral hepatitis. Patients with chronic hepatitis B superinfected with HEV may progress to liver failure. Babao Dan (BD) is a traditional Chinese medicine widely used as an auxiliary option for the treatment of chronic hepatitis and liver cancer in China. This study aimed to evaluate the effect of BD on the management of HEV infection in a rabbit model. Sixty-two specific-pathogen-free (SPF) rabbits were divided randomly into five groups and treated with BD or placebo for 2 weeks. All rabbits were inoculated intravenously with rabbit HEV after initial administration. Then, rabbits were administered BD or ribavirin or placebo at 2 weeks post-inoculation (wpi) until faecal virus shedding showed negative. The duration of faecal virus shedding and levels of HEV RNA in faeces were reduced, and anti-HEV antibodies were detected in all rabbits in groups treated with BD before or after inoculation. Ribavirin treatment rapidly cleared HEV infection in SPF rabbits, but anti-HEV antibodies remained negative in 50 % of rabbits treated with ribavirin. These results indicate that ribavirin treatment was more effective in clearing HEV infection, while administration of BD before or after inoculation was effective in clearing HEV infection. Further clinical studies are warranted.

Cavernous sinus thrombosis caused by contralateral sphenoid sinusitis: a case report

PubMed Central

2013-01-01

Objective To report a rare case of unilateral cavernous sinus thrombosis caused by contralateral sphenoid sinusitis. Case report A 33-year-old female visited our hospital for severe, right-sided, temporal headache, chemosis, periorbital edema, and proptosis. These signs were associated with congested erythematous nasal mucosa with purulent discharge from the right superior nasal meatus. Contrast enhanced CT showed dilated left superior ophthalmic vein, suggestive of thrombosis, contrast enhancement of the left cavernous sinuses, and dilation of cavernous sinus, indicating cavernous sinus inflammation. The right maxillary, ethmoid and sphenoid sinuses showed mucosal thickening and retention of purulent material. She was diagnosed with cavernous sinus thrombosis caused by contralateral sphenoid sinusitis. All clinical symptoms and signs improved after endoscopic sphenoidotomy and appropriate medical treatment. Conclusions Sphenoiditis can cause contralateral cavernous sinus thrombosis. Early surgical sphenoidotomy and aggressive medical treatment are the cornerstones of successful management of this life-threatening complication. PMID:23497466

Rabbit aortic aneurysm model with enlarging diameter capable of better mimicking human aortic aneurysm disease.

PubMed

Bi, Yonghua; Chen, Hongmei; Li, Yahua; Yu, Zepeng; Han, Xinwei; Ren, Jianzhuang

2018-01-01

The self-healing phenomenon can be found in the elastase-induced abdominal aortic aneurysm (AAA) model, and an enlarging AAA model was successfully induced by coarctation. Unfortunately, aortic coarctation in these enlarging models is generally not found in human AAA disease. This study aimed to create an experiment model of enlarging AAA in rabbits to better mimic human aortic aneurysm disease. Eighty-four male New Zealand white rabbits were randomly divided into three equal groups: two aneurysm groups (A and B) and a SHAM group. Aneurysm group rabbits underwent extrinsic aortic stenosis below the right renal artery and received a 10-minute incubation of 60 μl elastase (1 unit/μl). Absorbable suture was used in Group A and nonabsorbable cotton thread was used in Group B. A sham operation was performed in the SHAM group. Aortic diameter was measured after 1, 3, 7, and 15 weeks; thereafter animals were sacrificed for histopathological, immunohistochemical and quantitative studies. Two rabbits died at 29 and 48 days, respectively, after operation in Group B. All aneurysms formed and enlarged progressively by 3 weeks in the Aneurysm groups. However, diameter enlargement in Group A was significantly lower than that in Group B at 7 weeks. Aneurysm groups developed intimal hyperplasia; intima-media thickness (IMT) increased significantly by week 7, and aortic media thickness and intima-media ratio (IMR) increased significantly by week 15. Marked destruction of elastin fibers and smooth muscle cells (SMCs) occurred 1 week later and increased progressively thereafter. Intimal hyperplasia and SMCs content in Group A increased significantly by week 15 compared with Group B. Aneurysm groups exhibited strong expression of matrix metalloproteinases 2 and 9 and RAM11 by week 1, and decreased progressively thereafter. In conclusion, this novel rabbit AAA model enlarges progressively without coarctation and is capable of better mimicking human aortic aneurysm disease.

Efficacy of transsphenoidal surgery in achieving biochemical cure of growth hormone-secreting pituitary adenomas among patients with cavernous sinus invasion: a systematic review and meta-analysis.

PubMed

Briceno, Vanessa; Zaidi, Hasan A; Doucette, Joanne A; Onomichi, Kaho B; Alreshidi, Amer; Mekary, Rania A; Smith, Timothy R

2017-05-01

Growth hormone-secreting pituitary adenomas in adults can result in severe craniofacial disfigurement and potentially fatal medical complications. Surgical resection leading to remission of the disease is dependent on complete surgical resection of the tumor. Lesions that invade the cavernous sinus may not be safely accessible via an endonasal transsphenoidal surgery (TSS), and the rates of biochemical remission of patients with residual disease vary widely in the literature. We conducted a meta-analysis to examine the prevalence of biochemical remission after TSS among patients with growth hormone-secreting pituitary adenomas with and without cavernous sinus invasion. Embase, PubMed, and Cochrane Library databases were searched for relevant publications. Fourteen studies with 972 patients with biochemically confirmed growth hormone-secreting pituitary adenomas were included in the meta-analysis. The overall remission prevalence under a fixed-effect model was 47.6% (95% CI = 40.8-54.4%) for patients with invasive macroadenomas (I 2  = 74.6%, p < 0.01); 76.4% (95% CI = 72.2-80.1%) for patients with non-invasive macroadenomas (I 2  = 59.6%, p = 0.03); and 74.2% (95% CI = 66.3-80.7%) for patients with non-invasive microadenomas (I 2  = 36.4, p = 0.10). The significant difference among the three groups resulted from the difference between patients with or without cavernous sinus invasion (p = 0.01) and not from the size of adenomas among those without cavernous sinus invasion (p = 0.66). The prevalence of biochemical remission in patients with cavernous sinus invasion was lower than in patients without cavernous sinus invasion after TSS for acromegaly.

Optic nerve head axonal transport in rabbits with hereditary glaucoma.

PubMed

Bunt-Milam, A H; Dennis, M B; Bensinger, R E

1987-04-01

Rabbits with hereditary glaucoma develop ocular changes that resemble human congenital glaucoma and buphthalmia. The inheritance is autosomal recessive (bu). Previous research was performed primarily on albino bu/bu rabbits that were unhealthy and bred poorly. We have bred pigmented bu/bu rabbits to determine if this would improve hardiness and provide a better model for the disease in humans. First-generation offspring from matings of bu/bu albino with bu/bu pigmented rabbits were all affected, indicating that the bu gene is found at the same locus in both strains. The pigmented bu/bu offspring had a high degree of mortality, as reported previously for albino bu/bu rabbits. Newborn bu/bu rabbits initially had normal intraocular pressure (IOP; 15-23 mmHg); after 1- to 3 months, the IOP increased to 26-48 mmHg. The eyes became buphthalmic and the IOP returned to normal or sub-normal levels after 6-10 months. Since the lamina cribrosa is absent or poorly formed in the rabbit optic nerve head (ONH), this model was used to test the role of mechanical factors in the etiology of ONH pathology caused by increased IOP. Orthograde axonal transport was evaluated in both eyes from eight normal and 24 bu/bu rabbits of different ages, using intravitreal injections of [3H]leucine to mark orthograde axonal transport, followed by light- and electron-microscopic radioautography of the ONHs and superior colliculi. Normal rabbits of all ages showed no blockage of axonal transport in the ONH. All optic axons from young bu/bu rabbits with normal IOP and most axons from older buphthalmic rabbits that previously had elevated IOP were normal morphologically. Small zones of transport blockage occurred in bu/bu eyes while IOP was elevated; most affected axons lay immediately adjacent to ONH connective tissue beams that radiate outward from the central retinal vessels to the optic-nerve sheath. Thus, the rabbit, which lacks a true lamina cribrosa, does not show marked blockage of axonal transport as occurs in the LS of the monkey and cat ONH when IOP is elevated acutely. This anatomic difference appears to be protective against axonal damage, since bu/bu rabbits with chronic IOP elevation did not show significant loss of optic axons. These results are consistent with the proposed 'mechanical' theory of ONH damage resulting from increased IOP. Electron-microscopic radioautography revealed that chronically elevated IOP in bu/bu rabbits, which caused small foci of blocked ONH axonal transport against ONH beams, also caused degeneration of a few optic nerve terminals in the superior colliculi as the disease progressed.(ABSTRACT TRUNCATED AT 400 WORDS)

An Innovate Robotic Endoscope Guidance System for Transnasal Sinus and Skull Base Surgery: Proof of Concept.

PubMed

Friedrich, D T; Sommer, F; Scheithauer, M O; Greve, J; Hoffmann, T K; Schuler, P J

2017-12-01

Objective  Advanced transnasal sinus and skull base surgery remains a challenging discipline for head and neck surgeons. Restricted access and space for instrumentation can impede advanced interventions. Thus, we present the combination of an innovative robotic endoscope guidance system and a specific endoscope with adjustable viewing angle to facilitate transnasal surgery in a human cadaver model. Materials and Methods  The applicability of the robotic endoscope guidance system with custom foot pedal controller was tested for advanced transnasal surgery on a fresh frozen human cadaver head. Visualization was enabled using a commercially available endoscope with adjustable viewing angle (15-90 degrees). Results  Visualization and instrumentation of all paranasal sinuses, including the anterior and middle skull base, were feasible with the presented setup. Controlling the robotic endoscope guidance system was effectively precise, and the adjustable endoscope lens extended the view in the surgical field without the common change of fixed viewing angle endoscopes. Conclusion  The combination of a robotic endoscope guidance system and an advanced endoscope with adjustable viewing angle enables bimanual surgery in transnasal interventions of the paranasal sinuses and the anterior skull base in a human cadaver model. The adjustable lens allows for the abandonment of fixed-angle endoscopes, saving time and resources, without reducing the quality of imaging.

Three Variations in Rabbit Angiographic Stroke Models

PubMed Central

Culp, William C.; Woods, Sean D.; Brown, Aliza T.; Lowery, John D.; Hennings, Leah J.; Skinner, Robert D.; Borrelli, Michael J.; Roberson, Paula K.

2012-01-01

Purpose To develop angiographic models of embolic stroke in the rabbit using pre-formed clot or microspheres to model clinical situations ranging from transient ischemic events to severe ischemic stroke. Materials and Methods New Zealand White rabbits (N=151) received angiographic access to the internal carotid artery (ICA) from a femoral approach. Variations of emboli type and quantity of emboli were tested by injection into the ICA. These included fresh clots (1.0-mm length, 3–6 h), larger aged clots (4.0-mm length, 3 days), and 2 or 3 insoluble microspheres (700–900 μm). Neurological assessment scores (NAS) were based on motor, sensory, balance, and reflex measures. Rabbits were euthanized at 4, 7, or 24 hours after embolization, and infarct volume was measured as a percent of total brain volume using 2,3,5-triphenyltetrazolium chloride (TTC). Results Infarct volume percent at 24 hours after stroke was lower for rabbits embolized with fresh clot (0.45% ± 0.14%), compared with aged clot (3.52% ± 1.31%) and insoluble microspheres (3.39% ± 1.04%). Overall NAS (including posterior vessel occlusions) were positively correlated to infarct volume percent measurements in the fresh clot (r=0.50), aged clot (r=0.65) and microsphere (r=0.62) models (p<0.001). Conclusion The three basic angiographic stroke models may be similar to human transient ischemic attacks (TIA) (fresh clot), major strokes that can be thrombolysed (aged clot), or major strokes with insoluble emboli such as atheromata (microspheres). Model selection can be tailored to specific research needs. PMID:23142182

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 with neuronal loss in the brain. Development of any treatment or preventative measure is dependent upon a detailed understanding of the pathogenesis of these diseases, and understanding the mechanism by which certain species appear to be resistant to TSEs is critical. Rabbits are highly resistant to naturally acquired TSEs, and even under experimental conditions, induction of clinical disease is not easy. Using recombinant rabbit PrP as a model, this study describes critical molecular determinants that confer this high resistance to transmissible spongiform encephalopathies. PMID:28978705

[Therapeutic effects of gastric lavage with fuller earth combined with QingyiII catharsis in treatment of oral paraquat poisoning in rabbits].

PubMed

Lu, Yuanlan; Zhou, Manhong; Hu, Jie; Li, Jianguo

2015-04-01

To observe the therapeutic effects of gastric lavage with fuller earth combined with Qingyi II catharsis in treatment of oral paraquat poisoning in rabbits. Thirty healthy adult Japanese white rabbits were randomly divided into five groups: namely control group, model group, gastric lavage group (lavage of 10% fuller earth suspension), catharsis group (Qingyi II catharsis), and combination group (10 minutes after gastric lavage of fuller earth suspension liquid, giving Qingyi II for catharsis), with 6 rabbits in each group. All groups were challenged with paraquat (100 mg/kg) diluted to 5 mL with normal saline by lavage to reproduce the model of acute poisoning, while the control group was given 5 mL of normal saline instead. Each treatment group was treated accordingly at 1 hour after gavages of paraquat, and treatment continued for 3 days. The animal survival rate was observed. Venous blood samples were collected from ear marginal vein to determine the plasma concentration of paraquat by ultraviolet spectrophotometer at 1, 2, 4, 8 and 24 hours after the poisoning. The animals were sacrificed by intravenous air injection on the 8th day after the poisoning, and the right lower lobe of lung was harvested to observe the lung tissue pathological changes with hematoxylin-eosin (HE) staining. (1) Survival rate: the surviving rate of the combination group (6 rabbits) was higher than that of gastric lavage group (5 rabbits), catharsis group (2 rabbits) and model group (0 rabbit) on the 2nd day with statistically significant difference (P < 0.001). The survival rate on the 7th day in combination group (5 rabbits) was higher than that of gastric lavage group (3 rabbits), and catharsis group (0 rabbit ) with statistically significant difference (P = 0.003). (2) Plasma concentrations of paraquat: plasma paraquat concentration in all groups peaked at 2 hours after intoxication, and its levels in the gastric lavage, catharsis and combination groups were significantly lower than that of the model group ( mg/L: 1.830 ± 0.068, 1.890 ± 0.048, 1.800 ± 0.052 vs. 1.960 ± 0.063, all P < 0.01). As the time prolonged, the plasma concentration of paraquat was lowest in combination group than that of gastric lavage group and catharsis group (all P < 0.01). Gastric lavage and catharsis had interaction at 4 hours in combination group [F = 5.194, P = 0.034; the concentrations of paraquat (mg/L) was 0.670 ± 0.057 vs. 1.010 ± 0.018, 1.210 ± 0.052]. (3) Lung histopathology: obvious expansion and hyperemia of the alveolar capillary, widened alveolar septum, a large number of inflammatory cell infiltrations were observed in model group and catharsis group. Lung histopathology was more improved in combination group and gastric lavage group, and it was improved more obviously in combination group than that in gastric lavage group. Early start of gastric lavage with fuller earth combined with Qingyi II catharsis, can reduce the animal plasma concentrations of paraquat in oral paraquat poisoning rabbits. At the same time, it can alleviate the degree of lung injury and significantly improve survival rates compared with the single gastric lavage or catharsis alone. Gastric lavage with fuller earth combined with Qingyi II catharsis can improve the prognosis of animal synergistically.

Histotripsy and metastasis: Assessment in a renal VX-2 rabbit tumor model

NASA Astrophysics Data System (ADS)

Styn, Nicholas R.; Hall, Timothy L.; Fowlkes, J. Brian; Cain, Charles A.; Roberts, William W.

2012-10-01

Histotripsy is a non-invasive, pulsed ultrasound technology where controlled cavitation is used to homogenize targeted tissue. We sought to assess the possibility that histotripsy may increase metastatic spread of tumor by quantifying the number of lung metastasis apparent after histotripsy treatment of aggressive renal VX-2 tumor compared to nontreated controls. VX-2 tumor was implanted in the left kidneys of 28 New Zealand White rabbits. Twenty rabbits were treated with histotripsy (day 13 after implantation) while 8 served as controls. All rabbits underwent left nephrectomy (day 14) and then were euthanized (day 19). This study was powered to detect a doubling in metastatic rate. Homogenized tumor was seen in all treated nephrectomy specimens. Whole-mount, coronal lung sections were viewed to calculate number and density of metastases. Viable tumor was present in all 28 lungs examined. Histology confirmed fractionation of tumor in all treatment rabbits. There was not a statistical difference in total lung metastases (88.7 vs. 72.5; p=0.29) or metastatic density (8.9 vs. 7.0 mets/cm2; p=0.22) between treated and control rabbits. Further investigation is planned to validate these results in the VX-2 model and to assess metastatic rates in less aggressive tumors treated with histotripsy.

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.

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

PubMed

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

2015-05-01

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

Paranasal sinus bony structures and sinus functioning during viral colds in subjects with and without a history of recurrent sinusitis.

PubMed

Alho, Olli-Pekka

2003-12-01

The objective was to assess the impact of ostial obstruction and anatomical variations on paranasal sinus functioning during viral colds with computed tomography (CT) in subjects with and without a history of sinusitis. Cross-sectional study. Twenty-three volunteers with a history of recurrent sinusitis and 25 subjects without such history who had an early (symptoms for 2-4 d) natural cold were examined by taking viral specimens and CT scans and recording symptoms. The pathological sinus changes in the CT scans were scored, and several paranasal bony anatomical variations recorded. Viral origin of the cold was identified in 32 (67%) subjects, similarly in the two groups. Ostiomeatal obstruction and anatomical variations were equally frequent in the subjects with and without a sinusitis history (17 of 23 vs. 17 of 25 for ostial obstruction and 17 of 23 vs. 20 of 25 for at least one variation, respectively). However, in the case of ostiomeatal obstruction the combined CT score of ethmoidal and maxillary sinuses was significantly higher in the subjects with a sinusitis history than in those without (mean +/- SD, 3.0 +/- 0.9 vs. 2.3 +/- 1.2 [P =.05, t test]). In the sinusitis-prone subjects, several variations were associated significantly with various pathological sinus CT changes (septal deviation, horizontally situated processus uncinatus, large concha bullosa, and laterally concave concha media), whereas in the control subjects, only the presence of Haller cells was related to sphenoidal sinus disease. Ostiomeatal complex obstruction and bony anatomical variations seem to have a greater impact on the functioning of paranasal sinuses during viral colds in sinusitis-prone subjects than in subjects without a sinusitis history. These differences may be associated with the increased risk of bacterial sinusitis.

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

PubMed

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

2015-01-01

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

Power Doppler evaluation of joint effusions: investigation in a rabbit model.

PubMed

Strouse, P J; DiPietro, M A; Teo, E L; Doi, K; Chrisp, C E

1999-08-01

To study the power Doppler findings of septic arthritis and noninfectious synovitis in an animal model. The right knees of 10 rabbits were inoculated with an aqueous suspension of Staphylococcus aureus. The right knees of 5 rabbits were injected with talc suspension. The right knees of 5 rabbits were injected with saline. All 20 left knees were injected with saline. Serial power Doppler images were obtained using constant-imaging parameters. Images were reviewed by blinded observers who assessed for increased power Doppler signal. All 10 knees inoculated with S. aureus developed septic arthritis. Each infected rabbit knee demonstrated increased signal on power Doppler on at least one examination, ranging from 1-6 days after inoculation. Only 23 of 45 examinations of infected knees were unequivocally positive by power Doppler on examinations performed 1 to 6 days after inoculation. No knee with talc synovitis demonstrated increased power Doppler signal. No control knee demonstrated increased power Doppler signal. Increased power Doppler signal may be seen with septic arthritis; however, its intensity and timing may vary from subject to subject. A normal power Doppler examination does not exclude septic arthritis.

Proarrhythmic potential of halofantrine, terfenadine and clofilium in a modified in vivo model of torsade de pointes

PubMed Central

Batey, Andrew J; Coker, Susan J

2002-01-01

This study was designed to compare the proarrhythmic activity of the antimalarial drug, halofantrine and the antihistamine, terfenadine, with that of clofilium a K+ channel blocking drug that can induce torsade de pointes. Experiments were performed in pentobarbitone-anaesthetized, open-chest rabbits. Each rabbit received intermittent, rising dose i.v. infusions of the α-adrenoceptor agonist phenylephrine. During these infusions rabbits also received increasing i.v. doses of clofilium (20, 60 and 200 nmol kg−1 min−1), terfenadine (75, 250 and 750 nmol kg−1 min−1), halofantrine (6, 20 and 60 μmol kg−1) or vehicle. Clofilium and halofantrine caused dose-dependent increases in the rate-corrected QT interval (QTc), whereas terfenadine prolonged PR and QRS intervals rather than prolonging cardiac repolarization. Progressive bradycardia occurred in all groups. After administration of the highest dose of each drug halofantrine caused a modest decrease in blood pressure, but terfenadine had profound hypotensive effects resulting in death of most rabbits. The total number of ventricular premature beats was highest in the clofilium group. Torsade de pointes occurred in 6 out of 8 clofilium-treated rabbits and 4 out of 6 of those which received halofantrine, but was not seen in any of the seven terfenadine-treated rabbits. These results show that, like clofilium, halofantrine can cause torsade de pointes in a modified anaesthetized rabbit model whereas the primary adverse effect of terfenadine was cardiac contractile failure. PMID:11861329

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.

Geological features and evolution history of Sinus Iridum, the Moon

NASA Astrophysics Data System (ADS)

Qiao, Le; Xiao, Long; Zhao, Jiannan; Huang, Qian; Haruyama, Junichi

2014-10-01

The Sinus Iridum region is one of the important candidate landing areas for the future Chinese lunar robotic and human missions. Considering its flat topography, abundant geomorphic features and complex evolutionary history, this region shows great significance to both lunar science and landing exploration, including powered descent, surface trafficability and in-situ exploration. First, we use Lunar Reconnaissance Orbiter (LRO) Altimeter (LOLA) and Camera (LROC) data to characterize regional topographic and geomorphological features within Sinus Iridum, e.g., wrinkle ridges and sinuous rilles. Then, we deduce the iron and titanium content for the mare surface using the Clementine ultraviolet-visible (UVVIS) data and generate mineral absorption features using the Chandrayaan-1 Moon Mineralogy Mapper (M3) spectrometer data. Later, we date the mare surface using crater size-frequency distribution (CSFD) method. CSFD measurements show that this region has experienced four major lava infilling events with model ages ranging from 3.32 Ga to 2.50 Ga. The regional magmatic activities evolved from Imbrian-aged low-titanium to Eratosthenian-aged medium-titanium. The inner Sinus Iridum is mainly composed of pyroxene-rich basalts with olivine abundance increasing with time, while the surrounding highlands have a feldspar-dominated composition. In the northern wall of Sinus Iridum, some potential olivine-rich materials directly excavated from the lunar mantle are visible. The Sinus Iridum region is an ideal target for future landing exploration, we propose two candidate landing sites for the future Chinese robotic and human missions.

Etanercept Exacerbates Inflammation and Pathology in a Rabbit Model of Active Pulmonary Tuberculosis

PubMed Central

Tsenova, Liana; O'Brien, Paul; Holloway, Jennifer; Peixoto, Blas; Soteropoulos, Patricia; Fallows, Dorothy; Subbian, Selvakumar

2014-01-01

Treatment of chronic inflammatory diseases with tumor necrosis factor alpha (TNF-α) antagonists has been associated with increased risk of tuberculosis (TB). We examined the usefulness of the rabbit model of active pulmonary TB for studying the impact of the human immune modulatory reagent etanercept on the host immune response. Control of Mycobacterium tuberculosis (Mtb) infection, disease pathology, and the global transcriptional response in Mtb-infected lungs of rabbits were studied. Etanercept treatment exacerbated disease pathology and reduced bacillary control in the lungs, compared with infected untreated animals. Reduced collagen and fibrin deposition in the granulomas was associated with significant downregulation of the collagen metabolism and fibrosis network genes and upregulation of genes in the inflammatory response and cell recruitment networks in the lungs of etanercept treated, compared with untreated rabbits. Our results suggest that targeting the TNF-α signaling pathway disrupts the tissue remodeling process, which is required for the formation and maintenance of well-differentiated granulomas and for control of Mtb growth in the lungs. These results validate the use of the rabbit model for investigating the impact of selected human immune modulatory drugs, such as a TNF-α antagonist, on the host immune response and pathogenesis in TB. PMID:24831609

[Effect of nattokinase on restenosis after percutaneous transluminal angioplasty of the abdominal artery in rabbits].

PubMed

Gong, Min; Lin, Huan-bing; Wang, Qian; Xu, Jiang-ping

2008-08-01

To investigate the effect of nattokinase on intimal hyperplasia in rabbit abdominal artery after balloon injury and explore a novel strategy for the preventing restenosis after percutaneous transluminal angioplasty. Fifty-six New Zealand rabbits were randomly divided into 7 groups, namely the solvent control group, model group, natto extract lavage group, refined nattokinse lavage group, intravenous refined nattokinse injection group, clopidogrel group and clopidogrel-aspirin group. Balloon injury was induced by inserting the catheter through the femoral artery into the thoracic aorta of the rabbits. The platelet counts were notad and platelet aggregation was observed, and the abdominal artery was taken for pathological analysis. The expressions of MMP-2 and -9 in the abdominal artery were detected immunohistochemically. There was no significant difference in the platelet counts, platelet aggregation rate or MMP-2 and -9 expression between the model group and the nattokinse-treated groups (P>0.05). The stenosis index in each nattokinse-treated group was significantly greater and the neointimal proliferation index smaller than that of the model group (P<0.01 or 0.05). Nattokinse can inhibit restenosis of rabbit abdominal artery after percutaneous transluminal angioplasty, which is independent of its actions on the platelet or MMP-2 and -9 expressions.

Effect of Leukocyte-Rich and Platelet-Rich Plasma on Healing of a Horizontal Medial Meniscus Tear in a Rabbit Model

PubMed Central

Shin, Kyun Ho; Lee, Haseok; Kang, Seonghyun; Ko, You-Jin; Lee, Seung-Yup; Park, Jung-Ho; Bae, Ji-Hoon

2015-01-01

There are limited reports on the effect of platelet-rich plasma (PRP) on meniscus healing. The purpose of this study was to investigate the effect of leukocyte-rich PRP (L-PRP) on potential healing of the horizontal medial meniscus tears in a rabbit model. A horizontal medial meniscus tear was created in both knees of nine skeletally mature adult rabbits. Left or right knees were randomly assigned to a L-PRP group, or a control group. 0.5 mL of L-PRP from 10 mL of each rabbit's whole blood was prepared and injected into the horizontal tears in a L-PRP group. None was applied to the horizontal tears in a control group. The histological assessment of meniscus healing was performed at two, four, and six weeks after surgery. We found that there were no significant differences of quantitative histologic scoring between two groups at 2, 4, and 6 weeks after surgery (p > 0.05). This study failed to show the positive effect of single injection of L-PRP on enhancing healing of the horizontal medial meniscus tears in a rabbit model. Single injection of L-PRP into horizontal meniscus tears may not effectively enhance healing of horizontal medial meniscus tears. PMID:26180783

A microangiographic study of the effect of hyperthermia on the rabbit bladder

NASA Technical Reports Server (NTRS)

Hietala, S. O.; Howells, R.; Hazra, I. A.

1978-01-01

A model was used to study the effect of hyperthermia on a normal tissue. The model selected was the rabbit bladder and the end point measured was the changes in the micro-vasculature of the bladder wall. It was already demonstrated clinically that hot water bladder infusions produce regression in bladder tumors.

Histopathological and biomechanical evaluation of bone healing properties of DBM and DBM-G90 in a rabbit model.

PubMed

Meimandi Parizi, Abdolhamid; Oryan, Ahmad; Haddadi, Shahram; Bigham Sadegh, Amin

2015-01-01

The present study was designed to investigate the effects of DBM and DBM-G90 on bone healing in a rabbit model. Thirty male white albino rabbits were used in this study. An incision was made in all rabbits under general anesthesia directly over the radius in order to expose it. A 10-mm segmental defect was created on the middle portion of each radius. The defects of 10 rabbits (Group I) were filled with DBM Block and Strip (Zimmer, Inc., Warsaw, IN, USA), the defects of 10 rabbits (Group II) were filled with DBM soaked in G90, and the defects of 10 rabbits (Group III/control) were left empty. The rabbits were euthanized at 60 days postoperatively for histopathological and biomechanical evaluation. At the histopathologic level, the defects of the animals in the DBM and DBM-G90 groups showed more advanced healing criteria than those of the control group. In biomechanical findings, there was a statistically significant difference between the injured bones and contralateral normal bones of the control group in terms of measured strength. There was not a statistically significant difference between the treated bones of the DBM and DBM-G90 groups with contralateral normal bones, nor was there a statistically significant difference between the treated bones of the DBM and DBM-G90 groups with the treated bones of the control group, in terms of other biomechanical tests. Based on the histopathological and biomechanical findings, the DBM and DBM-G90 groups demonstrated superior osteogenic potential; however, G90 shows no superiority over DBM on bone healing.

Three-dimensional CAD/CAM imaging of the maxillary sinus in ageing process.

PubMed

Lovasova, Kvetuse; Kachlik, David; Rozpravkova, Mirela; Matusevska, Maria; Ferkova, Jana; Kluchova, Darina

2018-04-05

During the physiological ageing process atrophy of the alveolar bone appears in vertical direction. This bone resorption causes pushing the limits of the maxillary sinus at the expense of a degraded bone. The sinus volume increases due to the facial development in children and adolescents or during the ageing process due to the loss of teeth and bone mass. The main aim of this study is to determine the sinus shape and sinus floor morphology related to age. Human adult male and female cadaveric heads (aged 37 to 83 years) with different dental status were used. The three-dimensional CAD/CAM software was used to scan the solid impressions of the maxillary sinus to visualize the real sinus shape and sinus floor. Subsequently, other findings are shown in tables and evaluated graphically. The maxillary sinus morphology, its relationship to the nasal cavity, the sub sinus alveolar bone height, displacement of the lowest and highest points of sinus, and the sinus relationship to the roots of the upper teeth were studied and evaluated. Some septa, crests, and the prominent infraorbital canal were also found in the area of the sinus floor. This paper provides a unique view on the maxillary sinus and its changes during the ageing process with preserved topographical relations in a representative sample of the Slovak population. The visualization of the maxillary sinus anatomy is necessary in the diagnosis and treatment plans for dental implants and during current surgical procedures. Copyright © 2018 Elsevier GmbH. All rights reserved.

Does wet hair in cold weather cause sinus headache and posterior eye pain? A possible mechanism through selective brain cooling system.

PubMed

Kaya, Abdullah; Calışkan, Halil

2012-12-01

As a general observation, wet hair in cold weather seems to be a predisposing factor for sinus headache and posterior eye pain. We offer a mechanism through selective brain cooling system for this observation. Selective brain cooling (SBC) is a mechanism to protect brain from hyperthermia. Components of SBC are head skin and upper respiratory tract (nose and paranasal sinuses). Cool venous blood from head skin and mucous membranes of nose and paranasal sinuses drains to intracranial dural sinuses and provide brain cooling. Brain will be cooled very much when head skin exposes to hypothermia such a condition like wet hair in cold weather. We suggest that, in order to reduce brain cooling activity, some alterations are being occurred within paranasal sinuses. For this purpose, sinus ostiums may close and mucus may accumulate to reduce air within sinuses. Also there may be some vasomotor changes to prevent heat loss. We hypothesize that this possible alterations may occur within paranasal sinuses as a control mechanism for brain temperature control during exposure of head skin to hypothermia. Paranasal sinuses may also cool brain directly by a very thin layer of bone separates the posterior ethmoid air sinus from the subarachnoid space and only thin plates of bone separate the sphenoidal sinuses from internal carotid artery and cavernous sinuses. Because of their critical role in the SBC, posterior ethmoid air sinus and sphenoidal sinuses may be affected from this alterations more than other paranasal sinuses. This situation may cause posterior eye pain. This mechanism can explain why a person who expose to hypothermia with wet hair or a person who don't use a beret or a hat during cold weather gets sinus headache and posterior eye pain. These symptoms could lead to an incorrect diagnosis of sinusitis. Copyright © 2012 Elsevier Ltd. All rights reserved.

In vivo imaging in the rabbit as a model for the study of ovulation-inducing factors.

PubMed

Cervantes, M P; Palomino, J M; Adams, G P

2015-01-01

The study of factors responsible for eliciting ovulation in rabbits has been hampered by the lack of a suitable method of monitoring the ovaries in vivo. Ovarian imaging by ultrasound biomicroscopy was used in two experiments designed to determine the effects of seminal plasma on the ovulatory response in rabbits. In Experiment 1, female rabbits were group-housed and treated intramuscularly with saline, gonadotropin releasing hormone (GnRH), or seminal plasma of llamas or rabbits (n = 4 to 6 per group). Rabbits were euthanized eight days later to evaluate the ovarian response by ultrasound biomicroscopy ex situ. No differences among groups were detected in the proportion of rabbits that ovulated or in the number and size of corpora lutea. The high incidence of ovulation in the negative control group was unexpected, and confounded determination of an ovulation-inducing effect of seminal plasma. In Experiment 2, female rabbits were caged individually, and treated as in Experiment 1 (n = 5 to 7 per group). The ovarian response was evaluated in vivo by transcutaneous ultrasound biomicroscopy. Ovulation and formation of corpora lutea were detected only in rabbits given GnRH. A preovulatory surge in plasma luteinizing hormone concentration and a post-ovulatory rise in plasma progesterone concentration were detected only in rabbits treated with GnRH. Surgical translocation of the ovaries to a subcutaneous position enabled longitudinal assessment of the ovulatory response by ultrasound biomicroscopy. Results clearly documented the effect of physical/social interaction on ovulation in rabbits, and did not support the hypothesis that seminal plasma elicits ovulation in rabbits. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Induction of antibodies to nuclear antigens in rabbits by immunization with hydralazine-human serum albumin conjugates.

PubMed Central

Yamauchi, Y; Litwin, A; Adams, L; Zimmer, H; Hess, E V

1975-01-01

The antihypertensive drug hydralazine can induce in man a syndrome similar to spontaneous systemic lupus erythematosus (SLE). The pathogenesis of this drug-induced syndrome is not understood. In this investigation, five groups of rabbits were studied: group I, 10 rabbits hyperimmunized with hydralazine conjugated to human serum albumin (HSA) in complete Freund's adjuvant (CFA); group II, four rabbits with HSA in CFA; group III, four rabbits with CFA alone; group IV, five rabbits with hydralazine conjugated to rabbit serum albumin (RSA); and group V, four rabbits with a major metabolite of hydralazine conjugated to HSA. The rabbits immunized with hydralazine-HSA developed rising titers of antibodies to hydralazine and progressively increasing amounts of antibodies to both single-stranded and native DNA. The antibodies to DNA were cross-reactive with hydralazine as determined by inhibition of DNA binding and DNA hemagglutination tests. Similar results were obtained in rabbits immunized with the metabolite-HSA compound except the major hapten antibody response was to the metabolite. The DNA antibodies in this group were also capable of being absorbed by metabolite-HSA as well as hydralazine-HSA, indicative of the cross-reactivity between hydralazine and its metabolite. Immunization with hydralazine-RSA caused rabbits to produce antibodies to hydralazine but not to DNA, indicating the requirement for an immune response to the carrier protein in order for antibodies reactive with DNA to be produced. Thus, hyperimmunization of rabbits with hydralazine-protein conjugates may provide a useful animal model of SLE. The data suggests that an immune response to hydralazine may be important in human hydralazine-induced SLE. Images PMID:808562

Anatomy and Surgical Approaches to the Rabbit Nasal Septum.

PubMed

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

2017-09-01

The rabbit is the primary animal model used to investigate aspects of nasal surgery. Although several studies have used this model, none has provided a comprehensive analysis of the surgical anatomy and techniques used to gain access to the rabbit nasal fossae and septum. To describe and optimize the surgical anatomy and approach to the rabbit nasal vault and septal cartilage. In an ex vivo animal study conducted at an academic medical center, preliminary cadaveric dissections were performed on rabbit head specimens to establish familiarity with relevant anatomy and rehearse various approaches. Live Pasteurella-free New Zealand white rabbits (3.5-4.0 kg) were used to further develop this surgical technique developed here. Access of the nasal vault was gained through a midline nasal dorsum incision and creation of an osteoplastic flap with a drill. Submucosal resection was performed with preservation of the mucoperichondrium. All rabbits were monitored daily for 4 weeks in the postoperative period for signs of infection, pain, and complications. The study was conducted from June 1, 2014, to December 1, 2014. Surgical anatomy and techniques used to gain access to the rabbit nasal vault and harvest septal cartilage. Four Pasteurella-free New Zealand white rabbits (Western Organ Rabbit Co), ranging in age from 9 to 12 months and weighing between 3.5 and 4.0 kg, were used in this study. Initial dissections demonstrated the feasibility of harvesting septal cartilage while preserving the mucoperichondrial envelope. Access to the nasal vault through this 3-osteotomy approach allowed for maximal exposure to the nasal cavity bilaterally while maintaining the integrity of the mucoperichondrium following septal cartilage harvest. The maximum amount of bulk, en bloc, cartilage harvested was 1.0 × 2.5 cm. Following surgical dissection, all animals maintained adequate airway patency and support to midface structures. Furthermore, all specimens preserved the integrity of the mucoperichondrium, septum, vascular anatomy, and airway dynamics. No operative complications, postoperative airway compromise, or infections were observed. Access to the rabbit nasal vault and septal cartilage is feasible through a variety of surgical approaches and techniques. To date, this is the first study to meticulously document and review the surgical approaches to the rabbit nasal cavity. This approach describes a novel, 3-osteotomy method of accessing the nasal cavity bilaterally and successfully harvesting rabbit septal cartilage in a submucoperichondrial plane. The ability to preserve native anatomy and function allows for improved outcomes in translational and animal guided clinical research. NA.

Myxoma virus in the European rabbit: interactions between the virus and its susceptible host.

PubMed

Stanford, Marianne M; Werden, Steven J; McFadden, Grant

2007-01-01

Myxoma virus (MV) is a poxvirus that evolved in Sylvilagus lagomorphs, and is the causative agent of myxomatosis in European rabbits (Oryctolagus cuniculus). This virus is not a natural pathogen of O. cuniculus, yet is able to subvert the host rabbit immune system defenses and cause a highly lethal systemic infection. The interaction of MV proteins and the rabbit immune system has been an ideal model to help elucidate host/poxvirus interactions, and has led to a greater understanding of how other poxvirus pathogens are able to cause disease in their respective hosts. This review will examine how MV causes myxomatosis, by examining a selection of the identified immunomodulatory proteins that this virus expresses to subvert the immune and inflammatory pathways of infected rabbit hosts.

Single-Blinded Prospective Implementation of a Preoperative Imaging Checklist for Endoscopic Sinus Surgery.

PubMed

Error, Marc; Ashby, Shaelene; Orlandi, Richard R; Alt, Jeremiah A

2018-01-01

Objective To determine if the introduction of a systematic preoperative sinus computed tomography (CT) checklist improves identification of critical anatomic variations in sinus anatomy among patients undergoing endoscopic sinus surgery. Study Design Single-blinded prospective cohort study. Setting Tertiary care hospital. Subjects and Methods Otolaryngology residents were asked to identify critical surgical sinus anatomy on preoperative CT scans before and after introduction of a systematic approach to reviewing sinus CT scans. The percentage of correctly identified structures was documented and compared with a 2-sample t test. Results A total of 57 scans were reviewed: 28 preimplementation and 29 postimplementation. Implementation of the sinus CT checklist improved identification of critical sinus anatomy from 24% to 84% correct ( P < .001). All residents, junior and senior, demonstrated significant improvement in identification of sinus anatomic variants, including those not directly included in the systematic review implemented. Conclusion The implementation of a preoperative endoscopic sinus surgery radiographic checklist improves identification of critical anatomic sinus variations in a training population.

Vascular Complications of Intercavernous Sinuses during Transsphenoidal Surgery: An Anatomical Analysis Based on Autopsy and Magnetic Resonance Venography.

PubMed

Deng, Xuefei; Chen, Shijun; Bai, Ya; Song, Wen; Chen, Yongchao; Li, Dongxue; Han, Hui; Liu, Bin

2015-01-01

Vascular complications induced by intercavernous sinus injury during dural opening in the transsphenoidal surgery may contribute to incomplete tumour resections. Preoperative neuro-imaging is of crucial importance in planning surgical approach. The aim of this study is to correlate the microanatomy of intercavernous sinuses with its contrast-enhanced magnetic resonance venography (CE-MRV). Eighteen human adult cadavers and 24 patients were examined based on autopsy and CE-MRV. Through dissection of the cadavers and CE-MRV, the location, shape, number, diameter and type of intercavernous sinuses were measured and compared. Different intercavernous sinuses were identified by their location and shape in all the cadavers and CE-MRV. Compared to the cadavers, CE-MRV revealed 37% of the anterior intercavernous sinus, 48% of the inferior intercavernous sinus, 30% of the posterior intercavernous sinus, 30% of the dorsum sellae sinus and 100% of the basilar sinus. The smaller intercavernous sinuses were not seen in the neuro-images. According to the presence of the anterior and inferior intercavernous sinus, four types of the intercavernous sinuses were identified in cadavers and CE-MRV, and the corresponding operative space in the transsphenoidal surgical approach was implemented. The morphology and classification of the cavernous sinus can be identified by CE-MRV, especially for the larger vessels, which cause bleeding more easily. Therefore, CE-MRV provides a reliable measure for individualized preoperative planning during transsphenoidal surgery.

Sinus CT scan

MedlinePlus

CAT scan - sinus; Computed axial tomography scan - sinus; Computed tomography scan - sinus; CT scan - sinus ... Risks for a CT scan includes: Being exposed to radiation Allergic reaction to contrast dye CT scans expose you to more radiation than regular ...

Bottom's Semiology: The Duck-Rabbit and Magritte's Pipe.

ERIC Educational Resources Information Center

Berthoff, Ann E.

1993-01-01

Explores how a dyadic understanding of perception cancels the validity it might have as a model for the linguistic process. Discusses commonly misunderstood exhibits in the gallery of perception studies--the duck-rabbit and Magritte's pipe. (RS)

The modified polymethyl methacrylate-silicone keratoprosthesis in rabbit model.

PubMed

Sun, Heng; Hu, Zhu-Lin

2018-05-01

To evaluate the safety and effectiveness of a modified polymethyl methacrylate-silicone keratoprosthesis and its operation method in alkali-burned rabbit model. The polymethyl methacrylate-silicone keratoprostheses were implanted into seven alkali-burned rabbit corneas by a special operation method using autologous graft as the keratoprosthesis (Kpro) carrier. The long-term postoperative outcomes were evaluated. During a postoperative study period of 16 months, except for one Kpro extruded at 3 months, all Kpros were in good position and were kept transparent without Kpro extrusion, keratolysis, infection, endophthalmitis, or retinal detachment. The postoperative complications included elevated intraocular pressure in two cases and temporary retroprosthetic membrane formation in two cases. The modified polymethyl methacrylate-silicone Kpro and its operation method is a relatively safe and effective choice for alkali-burned rabbit eyes. Elevated intraocular pressure is the main complication needing to be resolved.

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

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.

The application of frontal sinus index and frontal sinus area in sex estimation based on lateral cephalograms among Han nationality adults in Xinjiang.

PubMed

Luo, Huifang; Wang, Jierui; Zhang, Shuang; Mi, Congbo

2018-05-01

The frontal sinus, due to its unique anatomical features, has become an important element in research for individual identification. Previous studies have demonstrated the use of frontal sinus as an indicator for sex discrimination; however, the sex discrimination rate using frontal sinus was lower compared to that using the traditional morphological methods. In order to improve the sex discrimination percentage, we developed a new method involving the measurement of the frontal sinus index and frontal sinus area from lateral cephalogram radiographs. In this study, 475 digital lateral cephalograms of adult Han citizens from Xinjiang were included. The maximum height, depth, and area of the frontal sinus were calculated using the NemoCeph NX software. The frontal sinus index (ratio of the maximum height to the depth of frontal sinus) was also computed. Statistical analysis results showed significant differences in the frontal sinus index and area between males and females. Discriminant function equation derived from this study differentiated between sexes with 76.6% accuracy. The results demonstrated that the use of frontal sinus index and area for sex discrimination was more accurate than using the frontal sinus index alone. Copyright © 2017. Published by Elsevier Ltd.

Effects of bileaflet mechanical heart valve orientation on coronary flow

NASA Astrophysics Data System (ADS)

Haya, Laura; Tavoularis, Stavros

2015-11-01

The aortic sinus is approximately tri-radially symmetric, but bileaflet mechanical heart valves (BMHVs), which are commonly used to replace diseased aortic valves, are bilaterally symmetric. This mismatch in symmetry suggests that the orientation in which a BMHV is implanted within the aortic sinus affects the flow characteristics downstream of it. This study examines the effect of BMHV orientation on the flow in the coronary arteries, which originate in the aortic sinus and supply the heart tissue with blood. Planar particle image velocimetry measurements were made past a BMHV mounted at the inlet of an anatomical aorta model under physiological flow conditions. The complex interactions between the valve jets, the sinus vortex and the flow in the right coronary artery were elucidated for three valve orientations. The coronary flow rate was directly affected by the size, orientation, and time evolution of the vortex in the sinus, all of which were sensitive to the valve's orientation. The total flow through the artery was highest when the valve was oriented with its axis of symmetry intersecting the artery's opening. The findings of this research may assist surgeons in choosing the best orientation for BMHV implantation. The bileaflet valve was donated by St. Jude Medical. Financial support was provided by the Natural Sciences and Engineering Research Council of Canada.

Comparison of Bovine Bone-Autogenic Bone Mixture Versus Platelet-Rich Fibrin for Maxillary Sinus Grafting: Histologic and Histomorphologic Study.

PubMed

Ocak, Hakan; Kutuk, Nukhet; Demetoglu, Umut; Balcıoglu, Esra; Ozdamar, Saim; Alkan, Alper

2017-06-01

Numerous grafting materials have been used to augment the maxillary sinus floor for long-term stability and success for implant-supported prosthesis. To enhance bone formation, adjunctive blood-born growth factor sources have gained popularity during the recent years. The present study compared the use of platelet-rich fibrin (PRF) and bovine-autogenous bone mixture for maxillary sinus floor elevation. A split-face model was used to apply 2 different filling materials for maxillary sinus floor elevation in 22 healthy adult sheep. In group 1, bovine and autogenous bone mixture; and in group 2, PRF was used. The animals were killed at 3, 6, and 9 months. Histologic and histomorphologic examinations revealed new bone formation in group 1 at the third and sixth months. In group 2, new bone formation was observed only at the sixth month, and residual PRF remnants were identified. At the ninth month, host bone and new bone could not be distinguished from each other in group 1, and bone formation was found to be proceeding in group 2. PRF remnants still existed at the ninth month. In conclusion, bovine bone and autogenous bone mixture is superior to PRF as a grafting material in sinus-lifting procedures.

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

PubMed Central

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

2017-01-01

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

Root Cause Analysis: An Examination of Odontogenic Origins of Acute Maxillary Sinusitis in Both Immunocompetent & Immunocompromised Patients.

PubMed

McCarty, Jennifer L; David, Ryan M; Lensing, Shelly Y; Samant, Rohan S; Kumar, Manoj; Van Hemert, Rudy L; Angtuaco, Edgardo J C; Fitzgerald, Ryan T

Dental and periodontal diseases represent important but often overlooked causes of acute sinusitis. Our goal was to examine the prevalence of potential odontogenic sources of acute maxillary sinusitis according to immune status and their associations with sinusitis. A retrospective review of maxillofacial computed tomography studies from 2013 to 2014 was performed. Each maxillary sinus and its ipsilateral dentition were evaluated for findings of acute sinusitis and dental/periodontal disease. Eighty-four patients (24 immunocompetent, 60 immunocompromised) had 171 maxillary sinuses that met inclusion criteria for acute maxillary sinusitis. Inspection of dentition revealed oroantral fistula in 1%, periapical lucencies in 16%, and projecting tooth root(s) in 71% of cases. Immunocompromised patients were more likely to have bilateral sinusitis than immunocompetent patients (67% vs 33%, P = 0.005). A paired case-control analysis in a subset of patients with unilateral maxillary sinusitis (n = 39) showed a higher prevalence of periapical lucency in association with sinuses that had an air fluid level-29% of sinuses with a fluid level had periapical lucency compared with 12% without sinus fluid (P = 0.033). Potential odontogenic sources of acute maxillary sinusitis are highly prevalent in both immunocompetent and immunocompromised patients, although the 2 patient populations demonstrate no difference in the prevalence of these potential odontogenic sources. Periapical lucencies were found to be associated with an ipsilateral sinus fluid level. Increased awareness of the importance of dental and periodontal diseases as key components of maxillofacial computed tomography interpretation would facilitate a more appropriate and timely treatment.

Torcular Herophili classification and evaluation of dural venous sinus variations using digital subtraction angiography and magnetic resonance venographies.

PubMed

Gökçe, Erkan; Pınarbaşılı, Tansu; Acu, Berat; Fırat, M Murat; Erkorkmaz, Ünal

2014-08-01

The configurations of cerebral veins and dural venous sinuses differ not only between individuals, but also between the two brain hemispheres of an individual, making the anatomical classification of the cerebral veins difficult. We evaluated the superior dural venous sinuses and classified their types and variations using magnetic resonance venography (MRV) and digital substraction angiography (DSA). A total of 394 patients were studied retrospectively. Superior dural venous sinuses were evaluated and the confluence of the sinuses was classified on 2-dimensional time-of-flight MRV, contrast-enhanced 3-dimensional spoiled gradient recalled echo magnetic resonance imaging, and/or cerebral DSA. Confluens sinuum was divided into three types: true confluence, partial confluence, and non-confluence. Of the three types, partial confluence (type II) was most frequently seen. Co-dominance of the transverse sinuses was most frequently observed. An occipital sinus was observed in 15 % of the patients. There were statistically significant differences between the left transverse sinus agenesis and the presence of the occipital sinus (p < 0.001), between the co-presence of the partial confluence type torcular and the occipital sinus (p = 0.040), and between the co-presence of the fenestrated straight sinus and the occipital sinus (p = 0.010). Although anatomical variations of dural venous sinuses are seen frequently, classification of venous sinuses helps surgeons in preoperative evaluation and management, and prevention of possible complications. In this study, we think that a comprehensive evaluation and classification of dural venous sinuses is a significant contribution to the literature.

Effects of total body irradiation and cyclosporin a on the lethality of toxic shock syndrome toxin-1 in a rabbit model of toxic shock syndrome.

PubMed

Dinges, Martin M; Gregerson, Dale S; Tripp, Timothy J; McCormick, John K; Schlievert, Patrick M

2003-10-15

Toxic shock syndrome (TSS) may be mediated by superantigen-activated T cells, a theory we tested in rabbits, which are more susceptible to the lethal effects of superantigens, such as TSS toxin-1 (TSST-1), than are mice. Rabbits exposed to 10 cGy of total body irradiation exhibited T cell deficiency, with profound depletion of splenic lymphocytes and circulating CD4(+) lymphocytes, as well as an inability to manifest delayed-type hypersensitivity. Nevertheless, these rabbits remained completely susceptible to TSST-1, indicating that TSS can occur in the setting of marked immunosuppression.

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

PubMed

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

2015-01-01

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

Extended Endoscopic and Open Sinus Surgery for Refractory Chronic Rhinosinusitis.

PubMed

Eloy, Jean Anderson; Marchiano, Emily; Vázquez, Alejandro

2017-02-01

This review discusses extended endoscopic and open sinus surgery for refractory chronic rhinosinusitis. Extended maxillary sinus surgery including endoscopic maxillary mega-antrostomy, endoscopic modified medial maxillectomy, and inferior meatal antrostomy are described. Total/complete ethmoidectomy with mucosal stripping (nasalization) is discussed. Extended endoscopic sphenoid sinus procedures as well as their indications and potential risks are reviewed. Extended endoscopic frontal sinus procedures, such the modified Lothrop procedure, are described. Extended open sinus surgical procedures, such as the Caldwell-Luc approach, frontal sinus trephine procedure, external frontoethmoidectomy, frontal sinus osteoplastic flap with or without obliteration, and cranialization, are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

The incidence of maxillary sinus membrane perforation during endoscopically assessed crestal sinus floor elevation: a pilot study.

PubMed

Garbacea, Antoanela; Lozada, Jaime L; Church, Christopher A; Al-Ardah, Aladdin J; Seiberling, Kristin A; Naylor, W Patrick; Chen, Jung-Wei

2012-08-01

Transcrestal sinus membrane elevation is a surgical procedure performed to increase the bone volume in the maxillary sinus cavity. Because of visual limitations, the potential for maxillary sinus membrane perforations may be greater than with the lateral approach technique. The aim of this study was to macroscopically investigate ex vivo the occurrence of sinus membrane perforation during surgery using 3 transcrestal sinus floor elevation methods. Twenty fresh human cadaver heads, with 40 intact sinuses, were used for simultaneous sinus membrane elevation, placement of graft material, and dental implants. Real-time sinus endoscopy, periapical digital radiographs, and cone-beam computerized tomography (CBCT) images were subsequently used to evaluate the outcome of each surgical procedure. Perforation rates for each of the 3 techniques were then compared using a significance level of P < .05. No statistically significant differences in the perforation rate (P = .79) were found among the 3 surgical techniques. Although the sinus endoscope noted a higher frequency of perforations at the time of implant placement as compared with instrumentation or graft insertion, the difference was not statistically significant (P = .04). The CBCT readings were judged to be more accurate for identifying evidence of sinus perforations than the periapical radiographs when compared with the direct visualization with the endoscope. This pilot study demonstrated that a sinus membrane perforation can occur at any time during the sinus lift procedure, independent of the surgical method used.

Repeated measurements of transfer factor in rabbits: an animal model suitable for evaluation of short-term exposure.

PubMed

Dahlqvist, M; Lagerstrand, L; Nilsen, A

1994-01-01

Acute temporary changes in lung function may be of use as a biological exposure indicator. However, studies of humans occupationally exposed to complex airborne irritants are often expensive and time demanding. Therefore, an animal model could be a valuable complement. A rabbit model has been evaluated where transfer factor was measured twice during the same day, and with the rabbit awake and available for exposure, in between. Anaesthesia and intubation in 22 rabbits (2.6 [0.2] kg [Mean (SD)]) were immediately followed by two measurements of transfer factor and alveolar volume. Transfer factor was estimated by the single breath CO-technique used in humans. The samples were analysed for CO and He on a gas chromatograph. After one pair of measurements the rabbit was allowed to wake up and after 5 h the duplicate measurements were repeated. The mean values of transfer factor, alveolar volume and transfer constant were 0.50 (0.09) mmol min-1 kPa-1, 127 (8) ml and 3.9 (0.6) mmol min-1 kPa-1 l-1, respectively. The intraindividual coefficients of variation were 7.3%, 5.3% and 6.7%, respectively. Five hours later when the duplicate measurements were repeated, transfer factor, alveolar volume and transfer constant were unchanged still. The results suggest that relatively small changes in transfer factor may be detected without losing power, and thus that this model could be used as a biological exposure indicator.

Development and hemocompatibility testing of nitric oxide releasing polymers using a rabbit model of thrombogenicity

PubMed Central

Major, Terry C; Handa, Hitesh; Annich, Gail M; Bartlett, Robert H

2014-01-01

Hemocompatibility is the goal for any biomaterial contained in extracorporeal life supporting (ECLS) medical devices. The hallmarks for hemocompatibility include nonthrombogenicity, platelet preservation and maintained platelet function. Both in vitro and in vivo assays testing for compatibility of the blood/biomaterial interface have been used over the last several decades to ascertain if the biomaterial used in medical tubing and devices will require systemic anticoagulation for viability. Over the last 50 years systemic anticoagulation with heparin has been the gold standard in maintaining effective ECLS. However, the biomaterial that maintains effective ECLS without the use of any systemic anticoagulant has remained elusive. In this review, the in vivo 4-h rabbit thrombogenicity model genesis will be described with emphasis on biomaterials that may require no systemic anticoagulation for ECLS longevity. These novel biomaterials may improve extracorporeal circulation (ECC) hemocompatibility by preserving near resting physiology of the major blood components, the platelets and monocytes. The rabbit ECC model provides a complete assessment of biomaterial interactions with the intrinsic coagulation players, the circulating platelet and monocytes. This total picture of blood/biomaterial interaction suggests that this rabbit thrombogenicity model could provide a standardization for biomaterial hemocompatibility testing. PMID:24934500

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 observed intercellular variability of rabbit ventricular action potential repolarisation.

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's adjuvant.

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 intercellular variability of rabbit ventricular action potential repolarisation. PMID:24587229

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

PubMed

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

2018-05-01

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

Excessive Premature Atrial Complexes and the Risk of Recurrent Stroke or Death in an Ischemic Stroke Population.

PubMed

Vinther, Kristina H; Tveskov, Claus; Möller, Sören; Auscher, Soren; Osmanagic, Armin; Egstrup, Kenneth

2017-06-01

Our aim was to investigate the association of premature atrial complexes and the risk of recurrent stroke or death in patients with ischemic stroke in sinus rhythm. In a prospective cohort study, we used 24-hour Holter recordings to evaluate premature atrial complexes in patients consecutively admitted with ischemic strokes. Excessive premature atrial complexes were defined as >14 premature atrial complexes per hour and 3 or more runs of premature atrial complexes per 24 hours. During follow-up, 48-hour Holter recordings were performed after 6 and 12 months. Among patients in sinus rhythm, the association of excessive premature atrial complexes and the primary end point of recurrent stroke or death were estimated in both crude and adjusted Cox proportional hazards models. We further evaluated excessive premature atrial complexes contra atrial fibrillation in relation to the primary end point. Of the 256 patients included, 89 had atrial fibrillation. Of the patients in sinus rhythm (n = 167), 31 had excessive premature atrial complexes. During a median follow-up of 32 months, 50 patients (30% of patients in sinus rhythm) had recurrent strokes (n = 20) or died (n = 30). In both crude and adjusted models, excessive premature atrial complexes were associated with the primary end point, but not with newly diagnosed atrial fibrillation. Compared with patients in atrial fibrillation, those with excessive premature atrial complexes had similarly high risks of the primary end point. In patients with ischemic stroke and sinus rhythm, excessive premature atrial complexes were associated with a higher risk of recurrent stroke or death. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

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

PubMed

Lavery, W J; Kiel, J W

2013-06-01

In humans, changing from upright to supine elicits an approximately 10 mmHg increase in cephalic venous pressure caused by the hydrostatic column effect, but episcleral venous pressure (EVP) and intraocular pressure (IOP) rise by only a few mmHg. The dissociation of the small increases in IOP and EVP compared to the larger increase in cephalic venous pressure suggests a regulatory mechanism controlling EVP. The aim of the present study was to determine if the rabbit model is suitable to study the effects of postural changes on EVP despite its short hydrostatic column. In anesthetized rabbits (n = 43), we measured arterial pressure (AP), IOP, and orbital venous pressure (OVP) by direct cannulation; carotid blood flow (BFcar) by transit time ultrasound, heart rate (HR) by digital cardiotachometer, and EVP with a servonull micropressure system. The goal of the protocol was to obtain measurement of supine EVP for ≈10 min, followed by ≈10 min of EVP measurement with the rabbit in a head down tilt. The data were analyzed by paired t-tests and the results reported as the mean ± standard error of the mean. In a separate group of animals (n = 35), aqueous flow was measured by fluorophotometry. This protocol entailed measurement of aqueous flow in the supine position for ≈60 min, followed by ≈60 min of aqueous flow measurement with the rabbit in a head down tilt. From supine to head down tilt, AP and BFcar were unchanged, IOP increased by 2.3 ± 0.4 mmHg (p < 0.001), EVP increased by 2.4 ± 0.4 mmHg (p < 0.001), OVP increased by 2.5 ± 0.2 mmHg (p < 0.001) and HR decreased by 9 ± 3 bpm (p = 0.002). Head down tilt caused no significant change in aqueous flow. Although the hydrostatic column in the rabbit is shorter than humans, the rabbit model permits sufficiently sensitive measurements of the pressures and systemic parameters likely involved in the EVP responses to posture change. The present results indicate directionally similar EVP and IOP responses to tilt as occur in humans and, as in humans, the responses are smaller than would be expected from the change in the hydrostatic column height. Also, as in humans, the model reveals no change in aqueous flow during head down tilt. We conclude the rabbit model is appropriate for studying the mechanisms responsible for the relative immunity of EVP and IOP to posture change. Copyright © 2013 Elsevier Ltd. All rights reserved.

Platelets Drive Thrombus Propagation in a Hematocrit and Glycoprotein VI-Dependent Manner in an In Vitro Venous Thrombosis Model.

PubMed

Lehmann, Marcus; Schoeman, Rogier M; Krohl, Patrick J; Wallbank, Alison M; Samaniuk, Joseph R; Jandrot-Perrus, Martine; Neeves, Keith B

2018-05-01

The objective of this study was to measure the role of platelets and red blood cells on thrombus propagation in an in vitro model of venous valvular stasis. A microfluidic model with dimensional similarity to human venous valves consists of a sinus distal to a sudden expansion, where for sufficiently high Reynolds numbers, 2 countercurrent vortices arise because of flow separation. The primary vortex is defined by the points of flow separation and reattachment. A secondary vortex forms in the deepest recess of the valve pocket characterized by low shear rates. An initial fibrin gel formed within the secondary vortex of a tissue factor-coated valve sinus. Platelets accumulated at the interface of the fibrin gel and the primary vortex. Red blood cells at physiological hematocrits were necessary to provide an adequate flux of platelets to support thrombus growth out of the valve sinus. A subpopulation of platelets that adhered to fibrin expose phosphatidylserine. Platelet-dependent thrombus growth was attenuated by inhibition of glycoprotein VI with a blocking Fab fragment or D-dimer. A 3-step process regulated by hemodynamics was necessary for robust thrombus propagation: First, immobilized tissue factor initiates coagulation and fibrin deposition within a low flow niche defined by a secondary vortex in the pocket of a model venous valve. Second, a primary vortex delivers platelets to the fibrin interface in a red blood cell-dependent manner. Third, platelets adhere to fibrin, activate through glycoprotein VI, express phosphatidylserine, and subsequently promote thrombus growth beyond the valve sinus and into the bulk flow. © 2018 American Heart Association, Inc.

Transcoronary sinus delivery of autologous bone marrow and angiogenesis in pig models with myocardial injury

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

Vicario, J.; Piva, J.; Pierini, A.

2002-06-01

Purpose: The aim of the investigation is to study myocardial injury on pig model with two objectives: (1) feasibility of stimulating angiogenesis with fresh autologous bone marrow; (2) administration of the same fresh autologous bone marrow via coronary sinus with transitory occlusion. Methods: A controlled study was done in animal model with three phases, in a study group of 12 pigs (bone marrow administration) as well as in control group of 4 pigs (saline administration). Phase 1--production of coronary stenosis and myocardial injury; Phase 2--two weeks later, administration of bone marrow through coronary sinus with 10 min occlusion in themore » study group and saline solution in the control group. Phase 3--two weeks later, histological staining with hematoxylin-eosin and inmunohistochemical staining with monoclonal antibody for smooth muscle {alpha}-actin were conducted on both study and control groups. Results: The percentage of angionenesis observed in the study group was 91% and 0% in control group. Counting of positive actin in affected and control areas showed statistically significant differences in relation to both groups: study group (1.37 vs. 0.79) and control group (0.47 vs. 0.51). The percentage of mononuclear immature cells observed in the myocardium in the study group was 25% and in the control group was 0%. There was no increment in the coronary collateral circulation when comparing coronary angiography. Conclusions: Autologous bone marrow in animal model with experimental myocardial injury enhances angiogenesis, as well as vessels with smooth muscles. The transitory occlusion of the coronary sinus might be an effective way to administer cells as those from the bone marrow.« less

Influence of female and male sex steroids on body composition in the rabbit model.

PubMed

Alexandersen, P; Hassager, C; Christiansen, C

2001-09-01

To study the influence on body composition of estrogen replacement therapy (ERT) in female rabbits and of replacement therapy with testosterone (TRT) in male rabbits using dual-energy X-ray absorptiometry (DEXA). Cholesterol-fed female and male rabbits receiving a weight-restricted diet (100 g/day) were used. Total lean tissue mass (LTM), total body fat tissue mass (FTM) and total tissue mass (TTM) were determined by DEXA at baseline, after which the animals were gonadectomized and treated with sex steroids. Soft body composition was then determined again after 30-31 weeks of treatment. Relative to controls, ERT with estradiol (E2) doses of 2 and 4 mg/day significantly increased LTM (p < 0.001), whereas E2 0.5 and 1 mg/day had a neutral effect on LTM. The change in fat mass, however, was not statistically significant between groups. In male rabbits, compared with castrated control rabbits, LTM decreased in testosterone-treated animals (by 7-12%; p < 0.001) but FTM decreased relatively more (by 66-79%; p < 0.0001). In both genders, body weight correlated with TTM as determined by DEXA (r = 0.89-0.91, p < 0.0001). In this in vivo model of growing rabbits, estrogen replacement significantly increased LTM in female animals, whereas testosterone replacement significantly decreased FTM in males, suggesting that soft body composition of both genders is significantly affected by replacement with sex steroids. Until comparable human data are available, it is speculated that similar changes in soft body composition may occur in humans treated with sex steroids.

Dietary consistency and plasticity of masseter fiber architecture in postweaning rabbits.

PubMed

Taylor, Andrea B; Jones, Kelly E; Kunwar, Ravinder; Ravosa, Matthew J

2006-10-01

Dietary consistency has been shown to influence cross-sectional area and fiber type composition of the masticatory muscles. However, little is known about the effects of dietary consistency on masticatory muscle fiber architecture. In this study, we explore the effects of dietary consistency on the internal architecture of rabbit masseter muscle. Because activity patterns of the rabbit chewing muscles show inter- and intramuscular heterogeneity, we evaluate if alterations in fiber architecture are homogeneous across various portions of the superficial masseter muscle. We compared masseter muscle fiber architecture between two groups of weanling rabbits raised on different diets for 105 days. One group was raised on a diet of ground rabbit pellets to model underuse of the masticatory complex, while the other group was fed a diet of intact pellets and hay blocks to model an overuse diet. In all portions of the superficial masseter, physiological cross-sectional areas (PCSAs) are greater in the overuse compared to underuse diet rabbits. Thus, the mechanical demands for larger muscle and bite forces associated with early and prolonged exposure to a tough diet are met by an increase in PCSA of the superficial masseter. The larger PCSA is due entirely to increased muscle mass, as the two rabbit groups show no differences in either fiber length or angle of pinnation. Thus, increasing pinnation angle is not a necessary biomechanical solution to improving muscle and bite force during growth. The change in PCSA but not fiber length suggests that variation in dietary consistency has an impact on maximum force production but not necessarily on excursion or contraction velocity.

Starling resistors, autoregulation of cerebral perfusion and the pathogenesis of idiopathic intracranial hypertension.

PubMed

DE Simone, Roberto; Ranieri, Angelo; Bonavita, Vincenzo

2017-03-01

Two critical functions for the control of intracranial fluids dynamics are carried on the venous side of the perfusion circuit: the first is the avoidance of cortical veins collapse during the physiological increases of cerebrospinal fluid (CSF) pressure in which they are immersed. The second, is the generation of an abrupt venous pressure drop at the confluence of the cortical veins with the dural sinuses that is required to allow a CSF outflow rate balanced with its production. There is evidence that both of these effects are ensured by a Starling resistor mechanism (a fluid dynamic construct that governs the flow in collapsible tubes exposed to variable external pressure) acting at the confluence of cortical veins in the dural sinus. This implies that, in normal circumstances of perfusion balance, a certain degree of venous collapse physiologically occurs at the distal end of the cortical vein. This is passively modulated by the transmural pressure of the venous wall (i.e. the difference between internal blood pressure and external CSF pressure). The mechanism provides that the blood pressure of the cortical vein upstream the collapsed segment is dynamically maintained a few mmHg higher than the CSF pressure, so as to prevent their collapse during the large physiological fluctuations of the intracranial pressure. Moreover, the partial collapse of the vein confluence also generates a sharp pressure drop of the blood entering into the sinus. The CSF is drained in dural sinus through arachnoid villi proportionally to its pressure gradient with the sinus blood. The venous pressure drop between cortical veins and dural sinus is therefore needed to ensure that the CSF can leave the cranio-spinal space with the same speed with which it is produced, without having to reach a too high pressure, which would compress the cortical veins. Notably, the mechanism requires that the walls of the dural sinuses are rigid enough to avoid the collapse under the external cerebrospinal fluid pressure, and predicts that in the presence of excessively flexible dural sinuses, the system admits a second point of balance between cerebral fluid pressure and dural sinus pressure, at higher values. The second balance state is due to the triggering of a self-limiting venous collapse feedback loop between the CSF pressure, that compresses the sinus, and the subsequent increase of the dural sinus pressure, that further raises the intracranial pressure. The loop may stabilize only when the maximum stretching allowed by the venous wall is reached. Then, a new relatively stable and self-sustaining balance state is achieved, at the price of a higher CSF and dural sinus pressure values. We propose that this model is crucially involved in Idiopatic Intracranial Hypertension pathogenesis with and without papilledema, a condition that could be described as a pathological new balance state, relatively stable, between intracranial and dural venous pressure, at higher absolute values.

The incidence and morphology of maxillary sinus septa in dentate and edentulous maxillae: a cadaveric study with a brief review of the literature

PubMed Central

Wabale, Rajendra Namdeo; Siddiqui, Abu Ubaida; Farooqui, Mujjebuddeen Samsudeen

2015-01-01

Objectives The aim of this study is to determine the incidence, location, and orientation of maxillary sinus septa in formalin embalmed cadavers. Materials and Methods The study was conducted on 210 cadaveric heads available in our department. After taking the mid-sagittal section the specimens were opened from the medial aspect and the sinus cavity was explored for the presence of maxillary sinus septa, their anatomical plane, location and dimensions. Results The mean linear distance between maxillary sinus floor and its anatomical ostium was 26.76±5.21 mm and 26.91±4.96 mm on right and left side, respectively. A total of 59 maxillary sinus septa (28.1%) were observed in 210 maxillary specimens. Septae were most common, 33 septa (55.9%), in the middle region (between first and second molar tooth) of the sinus cavity. The maxillary sinus membrane (Schneiderian membrane) adhered tightly to the maxillary sinus and over the septae. Significantly more maxillary sinus septa were observed in edentulous maxillae in comparison to the dentate upper jaw. Conclusion Knowledge of location of maxillary sinus ostium is mandatory for the rhinologist for drainage of secretions in maxillary sinusitis. The morphological details of maxillary sinus septa, particularly their location and anatomical planes, will guide dentists in performance of safe implant surgeries. The maxillary antrum septa of category I and II may complicate the procedure of inversion of bone plate and elevation of sinus membrane during maxillary augmentation surgeries. The category III septa observed in the sagittal plane were embedded by one of the branches of the infraorbital nerve in it, and if accidentally cut will lead to infraorbital nerve palsy in maxillary sinus surgeries. PMID:25741466

Acute microwave irradiation and cataract formation in rabbits and monkeys.

PubMed

Kramar, P; Harris, C; Emery, A F; Guy, A W

1978-09-01

Rabbits and monkeys were irradiated in the near field of a cavity-backed 2450 MHz resonant slot radiator, to determine the cataractogenic threshold. Rabbits developed cataracts at incident "apparent" power densities of 180 mW/cm2 (E2/120 pi, where E=rms/electric field strength). Monkeys sustained facial burns, but no lens damage, even at incident "apparent" power densities of 500 mW/cm2. These results were substantiated by computer thermal models.

Non-invasive evaluation of liver stiffness after splenectomy in rabbits with CCl4-induced liver fibrosis.

PubMed

Wang, Ming-Jun; Ling, Wen-Wu; Wang, Hong; Meng, Ling-Wei; Cai, He; Peng, Bing

2016-12-14

To investigate the diagnostic performance of liver stiffness measurement (LSM) by elastography point quantification (ElastPQ) in animal models and determine the longitudinal changes in liver stiffness by ElastPQ after splenectomy at different stages of fibrosis. Liver stiffness was measured in sixty-eight rabbits with CCl 4 -induced liver fibrosis at different stages and eight healthy control rabbits by ElastPQ. Liver biopsies and blood samples were obtained at scheduled time points to assess liver function and degree of fibrosis. Thirty-one rabbits with complete data that underwent splenectomy at different stages of liver fibrosis were then included for dynamic monitoring of changes in liver stiffness by ElastPQ and liver function according to blood tests. LSM by ElastPQ was significantly correlated with histologic fibrosis stage ( r = 0.85, P < 0.001). The optimal cutoff values by ElastPQ were 11.27, 14.89, and 18.21 kPa for predicting minimal fibrosis, moderate fibrosis, and cirrhosis, respectively. Longitudinal monitoring of the changes in liver stiffness by ElastPQ showed that early splenectomy (especially F1) may delay liver fibrosis progression. ElastPQ is an available, convenient, objective and non-invasive technique for assessing liver stiffness in rabbits with CCl 4 -induced liver fibrosis. In addition, liver stiffness measurements using ElastPQ can dynamically monitor the changes in liver stiffness in rabbit models, and in patients, after splenectomy.

Presentation of Preauricular Sinus and Preauricular Sinus Abscess in Southwest Nigeria

PubMed Central

Adegbiji, W. A.; Alabi, B. S.; Olajuyin, O. A.; Nwawolo, C. C.

2013-01-01

BACKGROUND AND AIM: Preauricular sinus abscess is a common congenital external ear disease. This abscess is usually misdiagnosed because it is commonly overlooked during physical examination. In Nigeria, the prevalence was 9.3% in Ilorin, north central Nigeria This study is to determine the distribution and clinical presentation of the preauricular sinus abscess in Ekiti, south west Nigeria. MATERIALS AND METHODS: This is a prospective hospital based study of all patients with diagnosis of preauricular sinus abscess seen in our clinic carried out between April 2008 to March 2010. Detailed clinical history, administered interviewer’s assisted questionnaires full examination and. Data obtained were collated and analysed. RESULTS: Preauricular sinus were noticed in 184 (4.4%) out of 4170 patients seen during the study period. Preauricular sinus abscess were noticed in 21 (11.4%) of the preauricular sinuses especially in children. Unilateral preauricular sinus abscess accounted for 90.5%. Common presenting complaints were preauricular swelling (81.0%), 90.5% with recurrent earaches, 76.2% with ear discharges. All patients had antibiotic / analgesic while 17 out of 21 (81.0%) had surgical excisions. CONCLUSION: Preauricular sinus abscess were noticed among 11.4% of the preauricular sinuses especially in children, unilateral preauricular sinus abscess accounted for 90.5%. Common complaints were otorrhoea, earaches, and swelling and they were mostly managed surgically. PMID:24711764

Development of the McGill simulator for endoscopic sinus surgery: a new high-fidelity virtual reality simulator for endoscopic sinus surgery.

PubMed

Varshney, Rickul; Frenkiel, Saul; Nguyen, Lily H P; Young, Meredith; Del Maestro, Rolando; Zeitouni, Anthony; Tewfik, Marc A

2014-01-01

The technical challenges of endoscopic sinus surgery (ESS) and the high risk of complications support the development of alternative modalities to train residents in these procedures. Virtual reality simulation is becoming a useful tool for training the skills necessary for minimally invasive surgery; however, there are currently no ESS virtual reality simulators available with valid evidence supporting their use in resident education. Our aim was to develop a new rhinology simulator, as well as to define potential performance metrics for trainee assessment. The McGill simulator for endoscopic sinus surgery (MSESS), a new sinus surgery virtual reality simulator with haptic feedback, was developed (a collaboration between the McGill University Department of Otolaryngology-Head and Neck Surgery, the Montreal Neurologic Institute Simulation Lab, and the National Research Council of Canada). A panel of experts in education, performance assessment, rhinology, and skull base surgery convened to identify core technical abilities that would need to be taught by the simulator, as well as performance metrics to be developed and captured. The MSESS allows the user to perform basic sinus surgery skills, such as an ethmoidectomy and sphenoidotomy, through the use of endoscopic tools in a virtual nasal model. The performance metrics were developed by an expert panel and include measurements of safety, quality, and efficiency of the procedure. The MSESS incorporates novel technological advancements to create a realistic platform for trainees. To our knowledge, this is the first simulator to combine novel tools such as the endonasal wash and elaborate anatomic deformity with advanced performance metrics for ESS.

Safety and Efficacy of OXB-202, a Genetically Engineered Tissue Therapy for the Prevention of Rejection in High-Risk Corneal Transplant Patients.

PubMed

Fouladi, Naghmeh; Parker, Maria; Kennedy, Vicky; Binley, Katie; McCloskey, Laura; Loader, Julie; Kelleher, Michelle; Mitrophanous, Kyriacos A; Stout, J Timothy; Ellis, Scott

2018-06-01

Due to both the avascularity of the cornea and the relatively immune-privileged status of the eye, corneal transplantation is one of the most successful clinical transplant procedures. However, in high-risk patients, which account for >20% of the 180,000 transplants carried out worldwide each year, the rejection rate is high due to vascularization of the recipient cornea. The main reason for graft failure is irreversible immunological rejection, and it is therefore unsurprising that neovascularization (NV; both pre and post grafting) is a significant risk factor for subsequent graft failure. NV is thus an attractive target to prevent corneal graft rejection. OXB-202 (previously known as EncorStat ® ) is a donor cornea modified prior to transplant by ex vivo genetic modification with genes encoding secretable forms of the angiostatic human proteins, endostatin and angiostatin. This is achieved using a lentiviral vector derived from the equine infectious anemia virus called pONYK1EiA, which subsequently prevents rejection by suppressing NV. Previously, it has been shown that rabbit donor corneas treated with pONYK1EiA substantially suppress corneal NV, opacity, and subsequent rejection in an aggressive rabbit model of cornea graft rejection. Here, efficacy data are presented in a second rabbit model, which more closely mirrors the clinical setting for high-risk corneal transplant patients, and safety data from a 3-month good laboratory practice toxicology and biodistribution study of pONYK1EiA-modified rabbit corneas in a rabbit corneal transplant model. It is shown that pONYK1EiA-modified rabbit corneas (OXB-202) significantly reduce corneal NV and the rate of corneal rejection in a dose-dependent fashion, and are tolerated with no adverse toxicological findings or significant biodistribution up to 13 weeks post surgery in these rabbit studies. In conclusion, angiogenesis is a valid target to prevent corneal graft rejection in a high-risk setting, and transplanted genetically modified corneas are safe and well-tolerated in an animal model. These data support the evaluation of OXB-202 in a first-in-human trial.

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

PubMed

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

2012-08-01

Advanced carotid atherosclerosis with severe stenosis (>70%) is a major clinical risk factor for ischemic stroke. Our ability to test new protocols for the treatment of atherosclerotic stenosis in humans is limited for obvious ethical reasons; therefore, a suitable animal model is required. The aim of this study was to generate an easily reproducible and inexpensive experimental rabbit carotid model of advanced atherosclerosis with morphological similarities to the human disease and the subsequent assessment of the reliability of B-mode ultrasound technology in the study of lumen area stenosis in this model. Briefly, New Zealand white rabbits underwent primary perivascular cold injury at the right common carotid artery followed by a 1.5% cholesterol-rich diet injury for eight weeks. All of the rabbits' arteries were imaged by B-mode ultrasound weekly, after which the rabbits were sacrificed, and their vessels were processed for histopathology. Ultrasound longitudinal view images from three cardiac cycles were processed by a new computerized analyzing method based on dynamic programming and maximum gradient algorithm for measurement of instantaneous changes in arterial wall thickness and lumen diameter in sequential ultrasound images. Histopathology results showed progressive changes, from the lipid-laden cells and fibrous connective tissue proliferation in neointimal layer, up to the fibro-lipid plaque formation, resulting in vessel wall thickening, remodeling and lumen stenosis. The B-mode ultrasound images and the histologic measurements showed an increase in the mean wall thickness and the lumen area stenosis within eight weeks. Quantitative and morphometric analysis of the mean wall thickness and the lumen area stenosis percentage showed a significant correlation between the B-mode ultrasound and the histological measurements at each time point (R = 0.989 and R = 0.995, p < 0.05, respectively). In conclusion, we successfully produced advanced atherosclerosis in the rabbit carotid artery that is similar to the condition seen in patients. This condition in rabbits can be properly assessed by B-mode ultrasound image processing. Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2012-03-01

Quantitative T2 mapping has been a widely used method for the evaluation of pathological cartilage properties, and the histological assessment system of osteoarthritis in the rabbit has been published recently. The aim of the study was to investigate the effectiveness of quantitative T2 mapping evaluation for articular cartilage lesions of a rabbit model of anterior cruciate ligament transection (ACLT) osteoarthritis. Twenty New Zealand White (NZW) rabbits were divided into ACLT surgical group and sham operated group equally. The anterior cruciate ligaments of the rabbits in ACLT group were transected, while the joints were closed intactly in sham operated group. Magnetic resonance (MR) examinations were performed on 3.0T MR unit at week 0, week 6, and week 12. T2 values were computed on GE ADW4.3 workstation. All rabbits were killed at week 13, and left knees were stained with Haematoxylin and Eosin. Semiquantitative histological grading was obtained according to the osteoarthritis cartilage histopathology assessment system. Computerized image analysis was performed to quantitate the immunostained collagen type II. The average MR T2 value of whole left knee cartilage in ACLT surgical group ((29.05±12.01) ms) was significantly higher than that in sham operated group ((24.52±7.97) ms) (P=0.024) at week 6. The average T2 value increased to (32.18±12.79) ms in ACLT group at week 12, but remained near the baseline level ((27.66±8.08) ms) in the sham operated group (P=0.03). The cartilage lesion level of left knee in ACLT group was significantly increased at week 6 (P=0.005) and week 12 (P<0.001). T2 values had positive correlation with histological grading scores, but inverse correlation with optical densities (OD) of type II collagen. This study demonstrated the reliability and practicability of quantitative T2 mapping for the cartilage injury of rabbit ACLT osteoarthritis model.

Species-specificity of equine and porcine Lawsonia intracellularis isolates in laboratory animals

PubMed Central

Sampieri, Francesca; Vannucci, Fabio A.; Allen, Andrew L.; Pusterla, Nicola; Antonopoulos, Aphroditi J.; Ball, Katherine R.; Thompson, Julie; Dowling, Patricia M.; Hamilton, Don L.; Gebhart, Connie J.

2013-01-01

Lawsonia intracellularis infection causes proliferative enteropathy (PE) in many mammalian species, with porcine and equine proliferative enteropathy (PPE and EPE) known worldwide. Hamsters are a well-published animal model for PPE infection studies in pigs. There is no laboratory animal model for EPE infection studies and it is not known whether there is species-specificity for equine or porcine isolates of L. intracellularis in animal models. The objective of this study was to determine whether it is possible to generate typical EPE lesions in hamsters after inoculation with an equine strain of L. intracellularis (EPE strain) and whether it is comparatively possible to generate PPE lesions in rabbits after inoculation with a porcine strain of L. intracellularis (PPE strain). In 2 separate trials, 4-week-old and 3-week-old weanling golden Syrian hamsters were challenged with EPE strains and compared to uninfected (both trials) and PPE-infected controls (Trial 2 only). Concurrently, 6 female New Zealand white juvenile rabbits were infected with PPE strain and observed concomitantly to 8 similar rabbits infected with EPE strain for a different experiment. Hamsters and rabbits were observed for 21 to 24 days post-infection (DPI), depending on the experiment. Neither infected species developed clinical signs. The presence of disease was assessed with diagnostic techniques classically used for pigs and horses: immune-peroxidase monolayer assay on sera; quantitative polymerase chain reaction (qPCR) detection of molecular DNA in feces; and hematoxylin and eosin (H&E) stain and immunohistochemistry (IHC) on intestinal tissues. Our results showed that EPE-challenged hamsters do not develop infection when compared with PPE controls (IHC, P = 0.009; qPCR, P = 0.0003). Conversely, PPE-challenged rabbits do not develop typical intestinal lesions in comparison to EPE-challenged rabbits, with serological response at 14 DPI being significantly lower (P = 0.0023). In conclusion, PPE and EPE strains appear to have different host-specificities for hamsters and rabbits, respectively. PMID:24124268

Radiographic, computed tomographic and surgical anatomy of the equine sphenopalatine sinus in normal and diseased horses.

PubMed

Tucker, R; Windley, Z E; Abernethy, A D; Witte, T H; Fiske-Jackson, A R; Turner, S; Smith, L J; Perkins, J D

2016-09-01

Knowledge of imaging anatomy, surgical anatomy and disorders affecting the sphenopalatine sinus are currently lacking. To describe the computed tomographic (CT) and surgical anatomy of the sphenopalatine sinus and diagnosis, treatment and outcome in clinical cases with sphenopalatine sinus disease. Cadaver observational study and retrospective case series. The sphenopalatine sinuses of 10 normal cadaver heads were examined with digital radiography, CT and sinoscopic examination prior to anatomical sectioning. Sphenopalatine sinus anatomy was described and compared between cadaver specimens across the imaging modalities. Medical records (January 2004-2014) of cases diagnosed with sphenopalatine sinus disease were reviewed. The anatomy of the sphenopalatine sinus was variable. The borders of the sphenopalatine sinus were not identifiable on plain radiographs, whereas CT provided useful anatomical information. The palatine portion of the sphenopalatine sinus was consistently accessible sinoscopically and the sphenoidal portion was accessible in 6/10 cadaver heads. Fourteen cases of sphenopalatine sinus disease were identified, presenting with one or more clinical signs of exophthalmos, blindness, unilateral epistaxis or unilateral nasal discharge. Diagnoses included neoplasia (7), progressive ethmoidal haematoma (4), sinus cyst (2) and empyema (1). Computed tomography provided diagnostic information but could not differentiate the nature of soft tissue masses. Standing sinoscopic access to the palatine portion of the sphenopalatine sinus was possible for evaluation, biopsy and resection of abnormal soft tissues. Surgical access to the sphenoidal portion was limited. Eight horses were alive at 1 year after diagnosis, with a worse outcome associated with CT evidence of bone loss and a diagnosis of neoplasia. Sphenopalatine sinus disease should be considered a rare cause of the clinical signs described. Knowledge of the anatomical variation of the sphenopalatine sinus is vital for interpreting CT images. A combination of CT and sinoscopy provides the most comprehensive approach for diagnosis and treatment of sphenopalatine sinus disease. © 2015 EVJ Ltd.

Management of acute maxillary sinusitis after sinus bone grafting procedures with simultaneous dental implants placement - a retrospective study.

PubMed

Chirilă, Lucian; Rotaru, Cristian; Filipov, Iulian; Săndulescu, Mihai

2016-03-08

The sinus lift was first described in 1974 and it has proven to be a predictable procedure ever since. The complications of this surgical procedure are reported in the literature to be low, and can include acute maxillary sinusitis, scattering of the grafting material into the sinus cavity, wound dehiscence and Schneiderian membrane perforations. We aimed to evaluate the rate of acute maxillary sinusitis after sinus lift procedures and the appropriate management strategies. Between 2013 and 2015, 245 dental implants were placed in 116 patients (76 males and 40 females) with concomitant bone augmentation of the maxillary sinus floor. The sinus lifting procedure was bilateral in 35 patients and unilateral in 81 patients (a total of 151 sinuses). Maxillary sinusitis occurred in 5 patients (4.3 %). The clinical signs of infection were: headache, locoregional pain, cacosmia, inflammation of the oral buccal mucosa and rhinorrhea or unilateral nasal discharge. A mucosal fistula was observed during inspection in one patient. The management included only the removal of the grafting material in 3 patients, in 1 patient the grafting material was removed together with all the implants, and in 1 patient only 2 implants and the grafting material were removed, 1 implant being left in place. The sinus cavity was irrigated with metronidazole solution and antibiotic therapy with clindamycin and metronidazole was prescribed for 10 days. Subsequently, all signs of infection disappeared within 5 to 7 days and normal sinus function and drainage were restored. Although sinus lift is regarded as a safe and reliable procedure, acute sinusitis is a possible complication which has to be managed immediately in order to reduce the risk of further complications like pansinusitis, osteomyelitis of the maxillary bone, and spreading of the infection in the infratemporal space or orbital cavity. To minimize risk, caution must be taken with all the steps of the procedure, in order not to obliterate the ostium, impairing maxillary sinus clearance.

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

PubMed

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

2009-02-01

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

Application of adipose-derived stem cells on scleral contact lens carrier in an animal model of severe acute alkaline burn.

PubMed

Espandar, Ladan; Caldwell, Delmar; Watson, Richard; Blanco-Mezquita, Tomas; Zhang, Shijia; Bunnell, Bruce

2014-07-01

To evaluate the therapeutic effect of human adipose-derived stem cells (hASCs) overlaid on a scleral contact lens (SCL) carrier in a rabbit model of ocular alkaline burn. After inducing alkaline burn in 11 New Zealand white rabbits, hASCs cultured on SCLs were placed on the right eye of 5 rabbits, SCLs without cells were used in 5, and no treatment was applied in 1 eye. Each eye was examined and photographed for corneal vascularization, opacities, and epithelial defect in week 1, 2, and 4 after surgery. After 1 month, rabbits were killed and the corneas were removed and cut in half for electron and light microscopy examination. Human adipose-derived stem cells were attached to SCL surface and confluent easily. Human adipose-derived stem cells on SCL eyes showed smaller epithelial defect, less corneal opacity, corneal neovascularization relative to SCL eyes. Both groups showed no symblepharon. However, the cornea in the untreated eye was melted in 2 weeks and developed severe symblepharon. Human adipose-derived stem cells on SCL can reduce inflammation and corneal haziness in severe ocular alkaline burn injury in rabbits.

Application of Adipose-Derived Stem Cells on Scleral Contact Lens Carrier in an Animal Model of Severe Acute Alkaline Burn

PubMed Central

Espandar, Ladan; Caldwell, Delmar; Watson, Richard; Blanco-Mezquita, Tomas; Zhang, Shijia; Bunnell, Bruce

2015-01-01

Purpose To evaluate the therapeutic effect of human adipose-derived stem cells (hASCs) overlaid on a scleral contact lens (SCL) carrier in a rabbit model of ocular alkaline burn. Materials and Methods After inducing alkaline burn in 11 New Zealand white rabbits, hASCs cultured on SCLs were placed on the right eye of 5 rabbits, SCLs without cells were used in 5, and no treatment was applied in 1 eye. Each eye was examined and photographed for corneal vascularization, opacities, and epithelial defect in week 1, 2, and 4 after surgery. After 1 month, rabbits were killed and the corneas were removed and cut in half for electron and light microscopy examination. Results Human adipose-derived stem cells were attached to SCL surface and confluent easily. Human adipose-derived stem cells on SCL eyes showed smaller epithelial defect, less corneal opacity, corneal neovascularization relative to SCL eyes. Both groups showed no symblepharon. However, the cornea in the untreated eye was melted in 2 weeks and developed severe symblepharon. Conclusion Human adipose-derived stem cells on SCL can reduce inflammation and corneal haziness in severe ocular alkaline burn injury in rabbits. PMID:24901976

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy improves survival of gastric cancer with peritoneal carcinomatosis: evidence from an experimental study

PubMed Central

2011-01-01

Background Cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) has been considered as a promising treatment modality for gastric cancer with peritoneal carcinomatosis (PC). However, there have also been many debates regarding the efficacy and safety of this new approach. Results from experimental animal model study could help provide reliable information. This study was to investigate the safety and efficacy of CRS + HIPEC to treat gastric cancer with PC in a rabbit model. Methods VX2 tumor cells were injected into the gastric submucosa of 42 male New Zealand rabbits using a laparotomic implantation technique, to construct rabbit model of gastric cancer with PC. The rabbits were randomized into control group (n = 14), CRS alone group (n = 14) and CRS + HIPEC group (n = 14). The control group was observed for natural course of disease progression. Treatments were started on day 9 after tumor cells inoculation, including maximal removal of tumor nodules in CRS alone group, and maximal CRS plus heperthermic intraperitoneal chemoperfusion with docetaxel (10 mg/rabbit) and carboplatin (40 mg/rabbit) at 42.0 ± 0.5°C for 30 min in CRS + HIPEC group. The primary endpoint was overall survival (OS). The secondary endpoints were body weight, biochemistry, major organ functions and serious adverse events (SAE). Results Rabbit model of gastric cancer with PC was successfully established in all animals. The clinicopathological features of the model were similar to human gastric PC. The median OS was 24.0 d (95% confidence interval 21.8 - 26.2 d ) in the control group, 25.0 d (95% CI 21.3 - 28.7 d ) in CRS group, and 40.0 d (95% CI 34.6 - 45.4 d ) in CRS + HIPEC group (P = 0.00, log rank test). Compared with CRS only or control group, CRS + HIPEC could extend the OS by at least 15 d (60%). At the baseline, on the day of surgery and on day 8 after surgery, the peripheral blood cells counts, liver and kidney functions, and biochemistry parameters were all comparable. SAE occurred in 0 animal in control group, 2 animals in CRS alone group including 1 animal death due to anesthesia overdose and another death due to postoperative hemorrhage, and 3 animals in CRS + HIPEC group including 1 animal death due to anesthesia overdose, and 2 animal deaths due to diarrhea 23 and 27 d after operation. Conclusions In this rabbit model of gastric cancer with PC, CRS alone could not bring benefit while CRS + HIPEC with docetaxel and carboplatin could significantly prolong the survival with acceptable safety. PMID:21548973

Lateral Sinus Dural Arteriovenous Fistulas: Sinovenous Outflow Restriction Outweighs Cortical Venous Reflux as a Parameter Associated with Hemorrhage.

PubMed

Hu, Yong-Sin; Lin, Chung-Jung; Wu, Hsiu-Mei; Guo, Wan-Yuo; Luo, Chao-Bao; Wu, Chih-Chun; Chung, Wen-Yuh; Liu, Kang-Du; Yang, Huai-Che; Lee, Cheng-Chia

2017-11-01

Purpose To investigate whether sinovenous outflow restriction (SOR) is more strongly associated with hemorrhage than cortical venous reflux (CVR) in patients with lateral sinus dural arteriovenous fistulas (DAVFs). Materials and Methods An institutional review board approved this retrospective study and waiver of informed consent was obtained. From 1995 to 2016, 163 cases of lateral sinus DAVFs were included and divided into hemorrhagic and nonhemorrhagic groups based on initial presentation. Their angiograms and magnetic resonance images were evaluated, with two evaluators independently grading CVR and SOR. The SOR was scored as the combined conduit score (CCS), ranging from zero (total occlusion) to 8 (fully patent). The CVR and CCS of the hemorrhagic and nonhemorrhagic groups were compared. Logistic regression models were established for both the CVR and CCS to compare their performances in discriminating DAVF hemorrhage. Results Sinovenous outflow was significantly more restrictive (lower median CCS) in the hemorrhagic group than in the nonhemorrhagic group (1 vs 6.5; P < .001). A CCS of less than or equal to 2 best discriminated between the groups with a sensitivity of 90.0% and a specificity of 88.1%. The CCS model had a higher discriminative performance than did the CVR model (area under the curve, 0.933 vs 0.843; P = .018). Conclusion The CCS grading system semiquantifies SOR. SOR may represent a stronger risk factor associated with hemorrhage in patients with lateral sinus DAVFs than does CVR, and thus may offer guidance in therapeutic decision making. © RSNA, 2017.

Development of a completely autologous valved conduit with the sinus of Valsalva using in-body tissue architecture technology: a pilot study in pulmonary valve replacement in a beagle model.

PubMed

Yamanami, Masashi; Yahata, Yuki; Uechi, Masami; Fujiwara, Megumi; Ishibashi-Ueda, Hatsue; Kanda, Keiichi; Watanabe, Taiji; Tajikawa, Tsutomu; Ohba, Kenkichi; Yaku, Hitoshi; Nakayama, Yasuhide

2010-09-14

We developed autologous prosthetic implants by simple and safe in-body tissue architecture technology. We present the first report on the development of autologous valved conduit with the sinus of Valsalva (BIOVALVE) by using this unique technology and its subsequent implantation in the pulmonary valves in a beagle model. A mold of BIOVALVE organization was assembled using 2 types of specially designed silicone rods with a small aperture in a trileaflet shape between them. The concave rods had 3 projections that resembled the protrusions of the sinus of Valsalva. The molds were placed in the dorsal subcutaneous spaces of beagle dogs for 4 weeks. The molds were covered with autologous connective tissues. BIOVALVEs with 3 leaflets in the inner side of the conduit with the sinus of Valsalva were obtained after removing the molds. These valves had adequate burst strength, similar to that of native valves. Tight valvular coaptation and sufficient open orifice area were observed in vitro. These BIOVALVEs were implanted to the main pulmonary arteries as allogenic conduit valves (n=3). Postoperative echocardiography demonstrated smooth movement of the leaflets with trivial regurgitation. Histological examination of specimens obtained at 84 days showed that the surface of the leaflet was covered by endothelial cells and neointima, including an elastin fiber network, and was formed at the anastomosis sides on the luminal surface of the conduit. We developed the first completely autologous BIOVALVE and successfully implanted these BIOVALVEs in a beagle model in a pilot study.

Use of negative air pressure by nasal suction during maxillary sinus floor lift: audit of 13 consecutive sinus grafts.

PubMed

Ucer, T C

2009-03-01

A common and serious intraoperative complication of sinus floor lift is perforation of the sinus lining. Several strategies to prevent or treat it have had varying results. We report the results of an audit of 13 consecutive sinus grafts in 11 patients in which nasal suction was used to facilitate raising the sinus lining, and to reduce the risk of perforation.

[Minimally invasive surgery for treating of complicated fronto-ethmoidal sinusitis].

PubMed

Pomar Blanco, P; Martín Villares, C; San Román Carbajo, J; Fernández Pello, M; Tapia Risueño, M

2005-01-01

Functional endoscopic sinus surgery (FESS) is nowadays the "gold standard" for frontal sinus pathologies, but management of acute situations and the aproach and/or the extent of the surgery perfomed in the frontal recess remains controversial nowadays. We report our experience in 4 patients with orbital celulitis due to frontal sinusitis who underwent combined external surgery (mini-trephination) and endoscopic sinus surgery. All patients managed sinus patency without any complications. We found this combined sinusotomy as an easy, effective and reproductible technique in order to resolve the difficult surgical management of complicated frontal sinusitis.

Chronic sinusitis associated with the use of unrecognized bone substitute: a case report.

PubMed

Beklen, Arzu; Pihakari, Antti; Rautemaa, Riina; Hietanen, Jarkko; Ali, Ahmed; Konttinen, Yrjö T

2008-05-01

Bone grafts are used for bone augmentation to ensure optimal implant placement. However, this procedure may sometimes cause sinusitis. The case of a 44-year-old woman with the diagnosis of recurrent and chronic sinusitis of her right maxillary sinus with a history of dental implant surgery is presented. After several attempts with normal standard sinusitis therapy, unrecognized bone substitute was removed from the sinus cavity, which finally led to resolution of the sinusitis. This case reiterates the importance of a careful examination, consultation, and second opinion for the selection of optimal treatment.

Endoscopic Modified Medial Maxillectomy for Fungal Ball of the Hypoplastic Maxillary Sinus With Bony Hypertrophy.

PubMed

Nomura, Kazuhiro; Ikushima, Hiroyuki; Ozawa, Daiki; Shimizu, Yuichi; Arakawa, Kazuya; Suzuki, Jun; Hidaka, Hiroshi; Katori, Yukio; Ohyama, Kenji

2018-05-01

Sinus fungal ball is defined as noninvasive chronic rhino-sinusitis with a clump of mold in the paranasal sinuses, typically affecting the maxillary sinus. Fairly good outcomes of endoscopic surgery have been reported where the ball is removed through the antrostomy. However, the affected sinus tends to have a smaller cavity and thicker bony walls. As such, it is often challenging to maintain a window size that is sufficient to control possible recurrence. The endoscopic modified medial maxillectomy procedure was applied to a 61-year old and a 70-year old female patient with maxillary sinus fungal ball. Using this method, we created a much larger inferior meatal antrostomy without difficulty. The window provided us with an endoscopic view of the whole sinus and complete eradication of the lesion. Endoscopic modified medial maxillectomy is useful as a surgical procedure for maxillary sinus fungal ball and should be considered for better outcomes.

Klotho protein lowered in senile patients with brady sinus arrhythmia.

PubMed

Wang, Ying; Yang, Wei; Zheng, Ernv; Zhang, Wei; Su, Xianming

2015-01-01

To explore the correlationship between brady sinus arrhythmia and the levels of serum klotho protein in aged. 104 patients over 75 years old with brady sinus arrhythmia (experiment group) were enrolled, including 34 cases of sinus arrest, 43 cases of sinus bradycardia and 25 cases of atrioventricular block. 109 patients over 75 years old without brady sinus arrhymia were chosen as control group. All subjects were monitored by Holter. The levels of serum klotho protein were detected and compared among three groups. The correlation between the frequency of sinus arrest and the levels of serum klotho protein was analyzed simultaneously. The levels of serum klotho protein in experiment group were lower than that in control group (P<0.01); the sinus arrest frequency was negatively correlated with the levels of serum klotho protien. The levels of serum klotho protein in patients with sinus arrest were lower than that with sinus bradycardia and atrioventricularblock (P<0.05). But there was no significant difference between sinus bradycardia group and atrioventricular block group. The levels of serum klotho protein may reflect the function of sinoatrial node and could be used as an index to estimate the function of sinoatrial node.

Klotho protein lowered in senile patients with brady sinus arrhythmia

PubMed Central

Wang, Ying; Yang, Wei; Zheng, Ernv; Zhang, Wei; Su, Xianming

2015-01-01

Objective: To explore the correlationship between brady sinus arrhythmia and the levels of serum klotho protein in aged. Methods: 104 patients over 75 years old with brady sinus arrhythmia (experiment group) were enrolled, including 34 cases of sinus arrest, 43 cases of sinus bradycardia and 25 cases of atrioventricular block. 109 patients over 75 years old without brady sinus arrhymia were chosen as control group. All subjects were monitored by Holter. The levels of serum klotho protein were detected and compared among three groups. The correlation between the frequency of sinus arrest and the levels of serum klotho protein was analyzed simultaneously. Results: The levels of serum klotho protein in experiment group were lower than that in control group (P<0.01); the sinus arrest frequency was negatively correlated with the levels of serum klotho protien. The levels of serum klotho protein in patients with sinus arrest were lower than that with sinus bradycardia and atrioventricularblock (P<0.05). But there was no significant difference between sinus bradycardia group and atrioventricular block group. Conclusion: The levels of serum klotho protein may reflect the function of sinoatrial node and could be used as an index to estimate the function of sinoatrial node. PMID:26550342

Bighorn sheep (Ovis canadensis) sinus tumors are associated with coinfections by potentially pathogenic bacteria in the upper respiratory tract.

PubMed

Fox, Karen A; Rouse, Natalie M; Huyvaert, Kathryn P; Griffin, Karen A; Killion, Halcyon J; Jennings-Gaines, Jessica; Edwards, William H; Quackenbush, Sandra L; Miller, Michael W

2015-01-01

Bighorn sheep (Ovis canadensis) sinus tumors are hyperplastic to neoplastic, predominantly stromal masses of the paranasal sinuses that expand the sinus lining and obstruct the sinus cavities. Obstruction of the sinus cavities and disruption of normal sinus lining anatomy may interfere with clearance of bacterial pathogens from the upper respiratory tract. To examine this possibility, we explored whether the presence of sinus tumor features (tumor score) affected the likelihood of detecting potentially pathogenic bacteria from upper respiratory sinus lining tissues in bighorn sheep. We developed or used existing PCR assays for the detection of leukotoxigenic Pasteurellaceae and Mycoplasma ovipneumoniae in sinus lining tissues collected from 97 bighorn sheep in Colorado, US from 2009 to 2012. With the use of logistic regression analyses we found that tumor score was a good predictor of the probability of detecting potentially pathogenic bacteria in sinus lining tissues; we were more likely to detect potentially pathogenic bacteria from samples with high tumor scores. These findings add to our understanding of possible mechanisms for the maintenance and shedding of bacterial agents from the upper respiratory tracts of bighorn sheep.

Survey of Current Practice Patterns in the Management of Frontal Sinus Fractures

PubMed Central

Choi, Kevin J.; Chang, Bora; Woodard, Charles R.; Powers, David B.; Marcus, Jeffrey R.; Puscas, Liana

2017-01-01

The management of frontal sinus fractures has evolved in the endoscopic era. The development of functional endoscopic sinus surgery (FESS) has been incorporated into management algorithms proposed by otolaryngologists, but the extent of its influence on plastic surgeons and oral and maxillofacial surgeons is heretofore unknown. A cross-sectional survey was performed to assess the practice pattern variations in frontal sinus fracture management across multiple surgical disciplines. A total of 298 surveys were reviewed. 33.5% were facial plastic surgeons with otolaryngology training, 25.8% general otolaryngologists, 25.5% plastic surgeons, and 15.1% oral and maxillofacial surgeons. 74.8% of respondents practiced in an academic setting. 61.7% felt endoscopic sinus surgery changed their management of frontal sinus fractures. 91.8% of respondents favored observation for uncomplicated, nondisplaced frontal sinus outflow tract fractures. 36.4% favored observation and 35.9% favored endoscopic sinus surgery for uncomplicated, displaced frontal sinus outflow tract fractures. For complicated, displaced frontal sinus outflow tract fractures, obliteration was more frequently favored by plastic surgeons and oral and maxillofacial surgeons than those with otolaryngology training. The utility of FESS in managing frontal sinus fractures appears to be recognized across multiple surgical disciplines. PMID:28523084

Prevalence of Sinus Tract in the Patients Visiting Department of Endodontics, Kermanshah School of Dentistry.

PubMed

Miri, Shima Sadat; Atashbar, Omid; Atashbar, Fardin

2015-04-23

Sinus tract is one of the manifestations of chronic dental infections, which is a path for the drainage of the infection and pus. The present study was aimed to investigate the prevalence of sinus tract with dental origin analyze the correlation between sinus tract and related factors. This study was conducted on 1527 patients, visiting Kermanshah school of dentistry, in 2014.The related teeth were examined in terms of vitality test and exact location of sinus tract. Moreover, the causes of this lesion and the needs for root canal treatment were assessed in these teeth. Having obtained the data from the patients, analyzed by Mann-Whitney, Chi-square tests. The frequency of sinus tract was 9.89% patients. There was a significant correlation between the prevalence of sinus tract and factors such as age, general health status, location of sinus tract and history of root canal treatment. The prevalence of sinus tract in maxilla was higher than the mandible (p=0.087). The prevalence of sinus tract in the posterior teeth (69.54%) was significantly higher than that of anterior teeth (30.46%) (p=0.000). From 724 teeth with periapical inflammation and radiolucency, 9.89% teeth had odontogenic sinus tract, and 23.42% teeth with history of root canal treatment had sinus tract. The most common cause of sinus tract incidence was previous root canal treatment. Therefore, clinicians need to pay a more attention to examining the posterior teeth referred for endodontic treatment.

Beneficial Effects of Pentanema vestitum Linn. Whole Plant on the Glucose and Other Biochemical Parameters of Alloxan Induced Diabetic Rabbits

PubMed Central

Ilahi, Ikram; Asghar, Ali; Ali, Shujat; Khan, Murad; Khan, Nasrullah

2012-01-01

The residents of Lower Dir and Malakand agency, Khyber Pakhtunkhwa, Pakistan, use the dry powder of whole plant of Pentanema vestitum for the treatment of asthma and diabetes. No documented reports are available about the therapeutic action of Pentanema vestitum. The present study was aimed to explore the antihyperglycemic effect of 70% methanol extract of Pentanema vestitum whole plant in glucose-induced nondiabetic hyperglycemic and alloxan-induced diabetic rabbits. During this study, the effects of plant extract on the serum lipid profile, GPT, ALP, bilirubin and creatinine of diabetic rabbits were also studied. The extract of Pentanema vestitum whole plant exhibited significant (P < 0.05) antihyperglycemic activity in glucose-induced hyperglycemic rabbits. Treatment of alloxan-induced diabetic rabbits with extract significantly (P < 0.05) reduced the elevated levels of serum glucose, GPT, ALP, bilirubin and creatinine. During the study of lipid profile, the extract proved to be antihyperlipidemic and HDL boosting in diabetic rabbit models. From the finding of the present research, it was concluded that the 70% methanol extract of Pentanema vestitum whole plant has beneficial effects on serum levels of glucose, lipid profile, GPT, ALP, bilirubin, and creatinine of diabetic rabbits. PMID:23316385

A model to measure fluid outflow in rabbit capsules post glaucoma implant surgery.

PubMed

Nguyen, Dan Q; Ross, Craig M; Li, Yu Qin; Pandav, Surinder; Gardiner, Bruce; Smith, David; How, Alicia C; Crowston, Jonathan G; Coote, Michael A

2012-10-05

Prior models of glaucoma filtration surgery assess bleb morphology, which does not always reflect function. Our aim is to establish a model that directly measures tissue hydraulic conductivity of postsurgical outflow in rabbit bleb capsules following experimental glaucoma filtration surgery. Nine rabbits underwent insertion of a single-plate pediatric Molteno implant into the anterior chamber of their left eye. Right eyes were used as controls. The rabbits were then allocated to one of two groups. Group one had outflow measurements performed at 1 week after surgery (n = 5), and group two had measurements performed at 4 weeks (n = 4). Measurements were performed by cannulating the drainage tube ostium in situ with a needle attached to a pressure transducer and a fluid column at 15 mm Hg. The drop in the fluid column was measured every minute for 5 minutes. For the control eyes (n = 6), the anterior chamber of the unoperated fellow eye was cannulated. Animals were euthanized with the implant and its surrounding capsule dissected and fixed in 4% paraformaldehyde, and embedded in paraffin before 6-μm sections were cut for histologic staining. By 7 days after surgery, tube outflow was 0.117 ± 0.036 μL/min/mm Hg at 15 mm Hg (mean ± SEM), whereas at 28 days, it was 0.009 ± 0.003 μL/min/mm Hg. Control eyes had an outflow of 0.136 ± 0.007 μL/min/mm Hg (P = 0.004, one-way ANOVA). Hematoxylin and eosin staining demonstrated a thinner and looser arrangement of collagenous tissue in the capsules at 1 week compared with that at 4 weeks, which had thicker and more densely arranged collagen. We describe a new model to directly measure hydraulic conductivity in a rabbit glaucoma surgery implant model. The principal physiologic endpoint of glaucoma surgery can be reliably quantified and consistently measured with this model. At 28 days post glaucoma filtration surgery, a rabbit bleb capsule has significantly reduced tissue hydraulic conductivity, in line with loss of implant outflow facility, and increased thickness and density of fibrous encapsulation.

An Upgrade on the Rabbit Model of Anthracycline-Induced Cardiomyopathy: Shorter Protocol, Reduced Mortality, and Higher Incidence of Overt Dilated Cardiomyopathy

PubMed Central

Talavera, Jesús; Fernández-Del-Palacio, María Josefa; García-Nicolás, Obdulio; Seva, Juan; Brooks, Gavin; Moraleda, Jose M.

2015-01-01

Current protocols of anthracycline-induced cardiomyopathy in rabbits present with high premature mortality and nephrotoxicity, thus rendering them unsuitable for studies requiring long-term functional evaluation of myocardial function (e.g., stem cell therapy). We compared two previously described protocols to an in-house developed protocol in three groups: Group DOX2 received doxorubicin 2 mg/kg/week (8 weeks); Group DAU3 received daunorubicin 3 mg/kg/week (10 weeks); and Group DAU4 received daunorubicin 4 mg/kg/week (6 weeks). A cohort of rabbits received saline (control). Results of blood tests, cardiac troponin I, echocardiography, and histopathology were analysed. Whilst DOX2 and DAU3 rabbits showed high premature mortality (50% and 33%, resp.), DAU4 rabbits showed 7.6% premature mortality. None of DOX2 rabbits developed overt dilated cardiomyopathy; 66% of DAU3 rabbits developed overt dilated cardiomyopathy and quickly progressed to severe congestive heart failure. Interestingly, 92% of DAU4 rabbits showed overt dilated cardiomyopathy and 67% developed congestive heart failure exhibiting stable disease. DOX2 and DAU3 rabbits showed alterations of renal function, with DAU3 also exhibiting hepatic function compromise. Thus, a shortened protocol of anthracycline-induced cardiomyopathy as in DAU4 group results in high incidence of overt dilated cardiomyopathy, which insidiously progressed to congestive heart failure, associated to reduced systemic compromise and very low premature mortality. PMID:26788502

A new simplified volume-loaded heterotopic rabbit heart transplant model with improved techniques and a standard operating procedure.

PubMed

Lu, Wei; Zheng, Jun; Pan, Xu-Dong; Li, Bing; Zhang, Jin-Wei; Wang, Long-Fei; Sun, Li-Zhong

2015-04-01

The classic non-working (NW) heterotopic heart transplant (HTX) model in rodents had been widely used for researches related to immunology, graft rejection, evaluation of immunosuppressive therapies and organ preservation. But unloaded models are considered not suitable for some researches. Accordingly, We have constructed a volume-loaded (VL) model by a new and simple technique. Thirty male New Zealand White rabbits were randomly divided into two groups, group NW with 14 rabbits and group VL with 16 rabbits, which served as donors and recipients. We created a large and nonrestrictive shunt to provide left heart a sufficient preload. The donor superior vena cave and ascending aorta (AO) were anastomosed to the recipient abdominal aorta (AAO) and inferior vena cava (IVC), respectively. No animals suffered from paralysis, pneumonia and lethal bleeding. Recipients' mortality and morbidity were 6.7% (1/15) and 13.3% (2/15), respectively. The cold ischemia time in group VL is slight longer than that in group NW. The maximal aortic velocity (MAV) of donor heart was approximately equivalent to half that of native heart in group VL. Moreover, the similar result was achieved in the parameter of late diastolic mitral inflow velocity between donor heart and native heart in group VL. The echocardiography (ECHO) showed a bidirectional flow in donor SVC of VL model, inflow during diastole and outflow during systole. PET-CT imaging showed the standard uptake value (SUV) of allograft was equal to that of native heart in both groups on the postoperative day 3. We have developed a new VL model in rabbits, which imitates a native heart hemodynamically while only requiring a minor additional procedure. Surgical technique is simple compared with currently used HTX models. We also developed a standard operating procedure that significantly improved graft and recipient survival rate. This study may be useful for investigations in transplantation in which a working model is required.

Protective effects of Xiongshao Capsule () on anti-inflammatory function of high-density lipoprotein in an atherosclerosis rabbit model.

PubMed

Zhang, Yan-Hong; Zhang, Ying; Li, Jing; Tong, Wen-Xin; Xu, Feng-Qin

2017-05-01

To observe the effects of Xiongshao Capsule (, XSC) on anti-inflflammatory properties of high-density lipoprotein (HDL), myeloperoxidase (MPO) and paraoxonase 1 (PON1) in serum of atherosclerosis (AS) rabbit model and explore the anti-inflflammatory protective effects of XSC on HDL. Sixty rabbits were randomized into the control, the model, XSC low-, medium- and high-dose (Rhizoma Chuanxiong + Radix Paeoniae rubra: 0.6+0.3, 1.2+0.6, 2.4+1.2g·kg -1 ·day -1 , respectively), and simvastatin (1g·kg -1 ·day -1 ) groups. The model rabbits were fed with high-fat diet and drugs for 15 weeks. The blood and thoracic aortas samples were collected at the end of 15 weeks. The levels of serum MPO and PON1 as well as total cholesterol (TC) and free cholesterol (FC) in aorta wall cells were tested by enzyme linked immunosorbent assay. TC and FC in the model group were significantly higher than those in the control group (P<0.01). Compared with the model group, TC and FC in the XSC groups were signifificantly lower (P<0.05 or P<0.01), so was simvastatin group (P<0.01). There was no signifificant difference in PON1 level between groups (P>0.05), even between model and control groups (P>0.05). The serum MPO level in the model group was signifificantly higher than that in the control group (P<0.05), which was signifificantly lower in XSC groups as well as simvastatin group (P<0.05 or P<0.01), and no difference was found between XSC groups and simvastatin group (P>0.05). XSC can reduce the serum MPO level in AS rabbits to protect the anti-inflammatory function of HDL, maintaining the normal lipid transport function. TC and FC levels in aorta cells decline, and this process initiated by XSC plays an anti-AS role.

Comparison of in vitro flows past a mechanical heart valve in anatomical and axisymmetric aorta models

NASA Astrophysics Data System (ADS)

Haya, Laura; Tavoularis, Stavros

2017-06-01

Flow characteristics past a bileaflet mechanical heart valve were measured under physiological flow conditions in a straight tube with an axisymmetric expansion, similar to vessels used in previous studies, and in an anatomical model of the aorta. We found that anatomical features, including the three-lobed sinus and the aorta's curvature affected significantly the flow characteristics. The turbulent and viscous stresses were presented and discussed as indicators for potential blood damage and thrombosis. Both types of stresses, averaged over the two axial measurement planes, were significantly lower in the anatomical model than in the axisymmetric one. This difference was attributed to the lower height-to-width ratio and more gradual contraction of the anatomical aortic sinus. The curvature of the aorta caused asymmetries in the velocity and stress distributions during forward flow. Secondary flows resulting from the aorta's curvature are thought to have redistributed the fluid stresses transversely, resulting in a more homogeneous stress distribution in the anatomical aortic root than in the axisymmetric root. The results of this study demonstrate the importance of modelling accurately the aortic geometry in experimental and computational studies of prosthetic devices. Moreover, our findings suggest that grafts used for aortic root replacement should approximate as closely as possible the shape of the natural sinuses.

Enzymatic recontouring of auricular cartilage in a rabbit model.

PubMed

Massengill, Phillip L; Goco, Paulino E; Norlund, L Layne; Muir-Padilla, Jeanne

2005-01-01

To evaluate the effectiveness of contouring auricular cartilage in a rabbit model using biologically active enzymes injected subcutaneously. The first phase determined the most effective volume and concentration required to affect the cartilage. To accomplish this task, we used ex vivo rabbit ears from a slaughterhouse. In the second phase, we injected 1 mL of hyaluronidase (150 U per milliliter of isotonic sodium chloride solution [saline]), elastase (1 mg per milliliter of saline), or saline into the ears of live rabbits. The study took place at the Madigan Army Medical Center (Tacoma, Wash), and included 10 animals. In each rabbit, we injected the test compound in one ear and saline in the other ear (control). We injected hyaluronidase in 5 ears and elastase in 5 ears. After injection, the ears were contoured and splinted for 4 weeks. In the third phase, we changed the injection pathway in 5 animals. At 4 weeks, 4 (80%) of the 5 ears injected with hyaluronidase showed full response and 1 (20%) had a partial response. Of the 5 ears injected with elastase, 4 (80%) showed a full response while 1 (20%) demonstrated a partial response. There was a response in all 10 of the ears injected with a test compound. Of the 10 control ears, 3 (30%) showed a partial response. At 6 weeks, approximately 6 (30%) of the ears had maintained contour demonstrating a full response. The difference between the test ears and the control ears was statistically significant (P = .006). Compared with the control ears, the results were statistically significant for elastase (P = .004) and hyaluronidase (P = .02). Overall, both agents demonstrated a subjective and objective response compared with control ears. This study demonstrates that bioactive enzymes and splinting can be effective in correcting ear deformities in a rabbit model.

Healing effects and superoxide dismutase activity of diode/Ga-As lasers in a rabbit model of osteoarthritis.

PubMed

Lee, Jae Yeon; Lee, Sang Ui; Lim, Taekjoo; Choi, Seok Hwa

2014-01-01

Osteoarthritis is a major cause of pain and disability in joints. The present study investigated the effects of differences of wavelengths and continuous versus pulsed delivery modes of low-level laser therapy (LLT) in a rabbit model of osteoarthritis. Comparison of the healing effects and superoxide dismutase (SOD) activity between therapy using diode and Ga-As lasers was our primary interest. Simple continuous wave (808-nm diode) and super-pulsed wave (904-nm Ga-As) lasers were used. Osteoarthritis was induced by injecting hydrogen peroxide into the articular spaces of the right stifle in rabbits. The rabbits were randomly assigned to four groups: normal control without osteoarthritis induction (G1), osteoarthritis-induction group without treatment (G2), osteoarthritis induction with diode irradiation (G3), and osteoarthritis induction with Ga-As irradiation (G4). Laser irradiation was applied transcutaneously for 5 min every day for over four weeks, starting the first day after confirmation of induction of osteoarthritis. The induction of osteoarthritis and effects of LLT were evaluated by biochemistry, computed tomography, and histological analyses. The SOD activity in G3 and G4 rabbits at two and four weeks after laser irradiation was significantly higher than that of G1 animals (p<0.05). However, there was no significant difference between G3 and G4 animals. Moreover, there were significant differences at two and four weeks between the control and osteoarthritis-induction groups, but no significant difference between G3 and G4 in the computed tomographic analyses and histological findings. These results indicate that diode and Ga-As lasers are similarly effective in healing and inducing SOD activity for LLT applications in a rabbit model of OA. Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Clinical recommendation for treatment planning of sinus augmentation procedures by using presurgical CAT scan images: a preliminary report.

PubMed

Kutkut, Ahmad M; Andreana, Sebastiano; Kim, Hyeong-Ll; Monaco, Edward

2011-12-01

To propose a clinical recommendation based on anatomy of maxillary sinus before sinus augmentation procedure using presurgical computerized axial tomography (CAT) scan images. CAT scan images were randomly selected from previous completed implant cases. Proposed area for the lateral window osteotomy was outlined on the panorex image of the CAT scan. Sagittal section on the CAT scan that was in the center of the outlined window was selected for sinus measurement analysis. On CAT scan, 2 lines were drawn to measure the dimensions of sinus. One line measured the horizontal width and the other line measured the vertical height. Based on the measurement data, a classification of the maxillary sinus anatomy was proposed. Narrow sinus cavity indicates favorable type anatomy in terms of bone regeneration healing and wide sinus cavity as less favorable anatomy for patient treatment planning. A narrow sinus and greater exposure to the blood supply should require shorter healing times after grafting. Conversely, wider sinus cavities and less exposure to the blood supply would require a longer healing time before implant placement.

The effect of deletion of the edema factor on Bacillus anthracis pathogenicity in guinea pigs and rabbits.

PubMed

Levy, Haim; Weiss, Shay; Altboum, Zeev; Schlomovitz, Josef; Rothschild, Nili; Glinert, Itai; Sittner, Assa; Kobiler, David

2012-01-01

Bacillus anthracis secretes three major components, which assemble into two bipartite toxins: lethal toxin (LT), composed of lethal factor (LF) and protective antigen (PA) and edema toxin (ET), composed of edema factor (EF) and PA. EF is a potent calmodulin-dependent adenylate cyclase, which is internalized into the target cell following PA binding. Once inside the cell, EF elevates cAMP levels, interrupting intracellular signaling. Effects of ET were demonstrated on monocytes, neutrophils and T-cells. In an earlier work we demonstrated that a deletion of LF in a fully virulent strain had no effect in guinea pigs and a significant, but not major, effect in the rabbit model. These results suggested that EF might play an important role in the development of infection and mortality following exposure to B. anthracis spores. To evaluate the role of EF in B. anthracis pathogenicity we deleted the cya gene, which encodes the EF protein, in the fully virulent Vollum strain. The Δcya mutant was fully virulent in the guinea pig model as determined by LD(50) experiments. In the rabbit model, when infected subcutaneously, the absence of EF had no effect on the virulence of the mutant. However an increase of two orders of magnitude in the LD(50) was demonstrated when the rabbits were infected by intranasal instillation accompanied with partial mortality and increased mean time to death. These results argue that in the guinea pig model the presence of one of the toxins, ET or LT is sufficient for the development of the infection. In the rabbit model ET plays a role in respiratory infection, most probably mediating the early steps of host colonization. Copyright © 2011 Elsevier Ltd. All rights reserved.

Acute Lung Injury and Persistent Small Airway Disease in a Rabbit Model of Chlorine Inhalation

PubMed Central

Musah, Sadiatu; Schlueter, Connie F.; Humphrey, David M.; Powell, Karen S.; Roberts, Andrew M.; Hoyle, Gary W.

2016-01-01

Chlorine is a pulmonary toxicant to which humans can be exposed through accidents or intentional releases. Acute effects of chlorine inhalation in humans and animal models have been well characterized, but less is known about persistent effects of acute, high-level chlorine exposures. In particular, animal models that reproduce the long-term effects suggested to occur in humans are lacking. Here, we report the development of a rabbit model in which both acute and persistent effects of chlorine inhalation can be assessed. Male New Zealand White rabbits were exposed to chlorine while the lungs were mechanically ventilated. After chlorine exposure, the rabbits were extubated and were allowed to survive for up to 24 h after exposure to 800 ppm chlorine for 4 min to study acute effects or up to 7 days after exposure to 400 ppm for 8 min to study longer term effects. Acute effects observed 6 or 24 h after inhalation of 800 ppm chlorine for 4 min included hypoxemia, pulmonary edema, airway epithelial injury, inflammation, altered baseline lung mechanics, and airway hyperreactivity to inhaled methacholine. Seven days after recovery from inhalation of 400 ppm chlorine for 8 min, rabbits exhibited mild hypoxemia, increased area of pressure-volume loops, and airway hyperreactivity. Lung histology 7 days after chlorine exposure revealed abnormalities in the small airways, including inflammation and sporadic bronchiolitis obliterans lesions. Immunostaining showed a paucity of club and ciliated cells in the epithelium at these sites. These results suggest that small airway disease may be an important component of persistent respiratory abnormalities that occur following acute chlorine exposure. This non-rodent chlorine exposure model should prove useful for studying persistent effects of acute chlorine exposure and for assessing efficacy of countermeasures for chlorine-induced lung injury. PMID:27913141

Stroke Location and Brain Function in an Embolic Rabbit Stroke Model

PubMed Central

Brown, Aliza T.; Skinner, Robert D.; Flores, Rene; Hennings, Leah; Borrelli, Michael J.; Lowery, John; Culp, William C.

2010-01-01

Purpose Current rabbit stroke models often depend on symptoms as endpoints for embolization and produce wide variation in location, size, and severity of strokes. To further refine our angiographic embolic stroke model we correlated localized infarctions to neurological deficits. Our goal is a rabbit model for long term studies of therapies after stroke. Materials and Methods New Zealand White rabbits (4–5 kg) (n=71) had selective internal carotid artery (ICA) angiography and a single clot was injected. At 24 hours neurological assessment scores (NAS) were measured on a 0=normal to 10=dead scale. Brains were removed and stained to identify stroke areas. All animals with single strokes, N=31, were analyzed by specific brain structure involvement and NAS values were correlated. Results Stroke incidence differed by location with cortex, subcortical, and basal ganglia regions highest. Distributions of middle cerebral artery (MCA) at 52% and anterior cerebral artery (ACA) at 29% were most commonly involved with largest stroke volumes in the ACA distribution. Brain stem and cerebellum strokes had disproportionately severe neurological deficits, scoring 2.25±1.0 vs. cortex (0.5±0.2), subcortical (1.3±0.4) and basal ganglia (0.5±0.3) all in the frontal or parietal regions on NAS (P≤0.02). Conclusions MCA and ACA distributions included 81% of strokes. These sites were relatively silent (potentially allowing longer term survival studies) while others in the posterior circulation produced disproportionately severe symptoms. Symptoms were not reliable indicators of stroke occurrence and other endpoints such as imaging may be required. These are important steps towards refinement of the rabbit stroke model. PMID:20417119

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

Sinus Anatomy

MedlinePlus

... ARS HOME ANATOMY Nasal Anatomy Sinus Anatomy Nasal Physiology Nasal Endoscopy Skull Base Anatomy Virtual Anatomy Disclosure ... ANATOMY > Sinus Anatomy Nasal Anatomy Sinus Anatomy Nasal Physiology Nasal Endoscopy Skull Base Anatomy Virtual Anatomy Disclosure ...

Neuro-ophthalmological presentation of non-invasive Aspergillus sinus disease in the non-immunocompromised host.

PubMed Central

Brown, P; Demaerel, P; McNaught, A; Revesz, T; Graham, E; Kendall, B E; Plant, G

1994-01-01

Two cases of non-invasive aspergillosis of the nose and paranasal sinuses are described. The first presented with left proptosis and ophthalmoplegia. Imaging and histology showed a maxillary sinus aspergilloma. The second case presented as a compressive optic neuropathy and histology showed allergic aspergillus sinusitis. The pathological distinction between invasive and non-invasive forms of aspergillus sinusitis is important as in invasive aspergillosis surgical treatment is most effectively combined with systemic antifungal treatment, whereas in aspergilloma of the paranasal sinuses surgical drainage of the sinuses alone is usually sufficient, and in allergic aspergillus sinusitis surgery is best combined with systemic or topical steroids. The distinction between invasive and non-invasive forms is particularly important as both may present with cranial neuropathies. Images PMID:8126516

Ontogeny of the Middle-Ear Air-Sinus System in Alligator mississippiensis (Archosauria: Crocodylia)

PubMed Central

Dufeau, David L.; Witmer, Lawrence M.

2015-01-01

Modern crocodylians, including Alligator mississippiensis, have a greatly elaborated system of pneumatic sinuses invading the cranium. These sinuses invade nearly all the bones of the chondrocranium and several bony elements of the splanchnocranium, but patterns of postnatal paratympanic sinus development are poorly understood and documented. Much of crocodylomorph—indeed archosaurian—evolution is characterized by the evolution of various paratympanic air sinuses, the homologies of which are poorly understood due in large part to the fact that individual sinuses tend to become confluent in adults, obscuring underlying patterns. This study seeks to explore the ontogeny of these sinuses primarily to clarify the anatomical relations of the individual sinuses before they become confluent and thus to provide the foundation for later studies testing hypotheses of homology across extant and extinct Archosauria. Ontogeny was assessed using computed tomography in a sample of 13 specimens covering an almost 19-fold increase in head size. The paratympanic sinus system comprises two major inflations of evaginated pharyngeal epithelium: the pharyngotympanic sinus, which communicates with the pharynx via the lateral (true) Eustachian tubes and forms the cavum tympanicum proprium, and the median pharyngeal sinus, which communicates with the pharynx via the median pharyngeal tube. Each of these primary inflations gives rise to a number of secondary inflations that further invade the bones of the skull. The primary sinuses and secondary diverticula are well developed in perinatal individuals of Alligator, but during ontogeny the number and relative volumes of the secondary diverticula are reduced. In addition to describing the morphological ontogeny of this sinus system, we provide some preliminary exploratory analyses of sinus function and allometry, rejecting the hypothesis that changes in the volume of the paratympanic sinuses are simply an allometric function of braincase volume, but instead support the hypothesis that these changes may be a function of the acoustic properties of the middle ear. PMID:26398659

Long-term patency of complex bilobular, bisaccular, and broad-neck aneurysms in the rabbit microsurgical venous pouch bifurcation model.

PubMed

Marbacher, Serge; Tastan, Ilhan; Neuschmelting, Volker; Erhardt, Salome; Coluccia, Daniel; Sherif, Camillo; Remonda, Luca; Fandino, Javier

2012-07-01

In experimental aneurysm models, long-term patency without spontaneous thrombosis is the most important precondition for analyses of embolization devices. We recently reported the feasibility of creating complex venous pouch bifurcation aneurysms in the rabbit with low morbidity, low mortality, and high short-term aneurysm patency. In order to further evaluate our model, we examined the long-term patency rate. Various sizes of complex bilobular, bisaccular, and broad-neck venous pouch aneurysms were surgically formed at an artificially created bifurcation of both common carotid arteries in 17 rabbits. Early aggressive anticoagulation was continued for 1 month. The rabbits were followed up using contrast-enhanced three-dimensional 1.5-T magnetic resonance angiography (CE-3D-MRA) at 1 month and up to 1 year after creation of the bifurcation. At 1-month follow-up, all but one of the created aneurysms and all parent vessels proved to be patent. Three animals (18%) were lost during follow-up for reasons unrelated to aneurysm surgery. At 1-year follow-up, one animal showed partial and one complete spontaneous aneurysm thrombosis (aneurysm patency rate: 86%). Six out of 42 parent vessels were occluded at that time (vessel patency rate: 86%). Complex bilobular, bisaccular, and broad-neck microsurgical aneurysm formation in the rabbit bifurcation model demonstrates a high long-term patency rate but is complicated by high rates of unrelated procedural mortality and morbidity. There is no need for prolonged (>4 weeks) anticoagulation to achieve good long-term patency in complex venous pouch bifurcation aneurysms.

Therapeutic effects of liposome-enveloped Ligusticum chuanxiong essential oil on hypertrophic scars in the rabbit ear model.

PubMed

Zhang, Hong; Ran, Xia; Hu, Chang-Ling; Qin, Lu-Ping; Lu, Ying; Peng, Cheng

2012-01-01

Hypertrophic scarring, a common proliferative disorder of dermal fibroblasts, results from an overproduction of fibroblasts and excessive deposition of collagen. Although treatment with surgical excision or steroid hormones can modify the symptoms, numerous treatment-related complications have been described. In view of this, we investigated the therapeutic effects of essential oil (EO) from rhizomes of Ligusticum chuanxiong Hort. (Umbelliferae) on formed hypertrophic scars in a rabbit ear model. EO was prepared as a liposomal formulation (liposome-enveloped essential oil, LEO) and a rabbit ear model with hypertrophic scars was established. LEO (2.5, 5, and 10%) was applied once daily to the scars for 28 days. On postoperative day 56, the scar tissue was excised for masson's trichrome staining, detection of fibroblast apoptosis, assays of the levels of collagens I and III, and analysis of the mRNA expression of matrix metalloproteinase-1 (MMP-1), caspase-3 and -9, and transforming growth factor beta 1 (TGF-β(1)). In addition, the scar elevation index (SEI) was also determined. As a result, LEO treatment significantly alleviated formed hypertrophic scars on rabbit ears. The levels of TGF-β(1), MMP-1, collagen I, and collagen III were evidently decreased, and caspase -3 and -9 levels and apoptosis cells were markedly increased in the scar tissue. SEI was also significantly reduced. Histological findings exhibited significant amelioration of the collagen tissue. These results suggest that LEO possesses the favorable therapeutic effects on formed hypertrophic scars in the rabbit ear model and may be an effective cure for human hypertrophic scars.

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.

Modulation of Vasomotive Activity in Rabbit External Ophthalmic Artery by Neuropeptides

PubMed Central

Delgado, Esmeralda Sofia Costa; Marques-Neves, Carlos; Rocha, Maria Isabel Sousa; Sales-Luís, José Paulo Pacheco; Silva-Carvalho, Luís Filipe

2012-01-01

Purpose. To investigate the vasomotive activity upon the external ophthalmic artery of vasointestinal peptide (VIP) and neuropeptide Y (NPY) using a previously developed model. Methods. Isolated rabbit eyes (n = 12) were perfused in situ with tyrode through the external ophthalmic artery. Effects of intra-arterial injections of NPY 200 μg/ml (Group A; n = 6) and VIP 200 μg/ml (Group B; n = 6) on the recorded pressure were obtained. For statistical analysis, Student's paired t-test and Fast Fourier Transform were used. Results. Spontaneous oscillations were observed before any drug administration in the 12 rabbit models. NPY produced an increase in total vascular resistance and a higher frequency and amplitude of oscillations, while VIP evoked the opposite effects. Conclusions. This study provides evidence of vasomotion in basal conditions in rabbit external ophthalmic artery. Concerning drug effects, NPY increased arterial resistance and enhanced vasomotion while VIP produced opposite effects which demonstrates their profound influence in arterial vasomotion. PMID:22496962

Sinus Headaches

MedlinePlus

... Achy feeling in your upper teeth Sinusitis or migraine? Migraines and headaches from sinusitis are easy to confuse ... types of headaches may overlap. Both sinusitis and migraine headache pain often gets worse when you bend ...

Sick Sinus Syndrome

MedlinePlus

... rhythm problems (arrhythmias) in which the heart's natural pacemaker (sinus node) doesn't work properly. The sinus ... people with sick sinus syndrome eventually need a pacemaker to keep the heart in a regular rhythm. ...

Variations in magnetic resonance venographic anatomy of the dorsal dural venous sinus system in 51 dogs.

PubMed

Fenn, Joe; Lam, Richard; Kenny, Patrick J

2013-01-01

Variations in intracranial dural venous sinus anatomy have been widely reported in humans, but there have been no studies reporting this in dogs. The purpose of this retrospective study was to describe variations in magnetic resonance (MR) venographic anatomy of the dorsal dural venous sinus system in a sample population of dogs with structurally normal brains. Medical records were searched for dogs with complete phase contrast, intracranial MR venograms and a diagnosis of idiopathic epilepsy. Magnetic resonance venograms were retrieved for each dog and characteristics of the dorsal dural sinuses, symmetry of the transverse sinuses and other anatomic variations were recorded. A total of 51 dogs were included. Transverse sinus asymmetry was present in 58.8% of the dogs, with transverse sinus hypoplasia seen in 39.2%, and aplasia in 23.5% of dogs. For 70.6% of dogs, at least one anatomic variation in the dorsal sagittal sinus was observed, including deviation from the midline (33.3%) and collateral branches from either the dorsal sagittal sinus or dorsal cerebral veins (54.9%). In 5 dogs (9.8%) a vessel was also identified running from the proximal transverse sinus to the distal sigmoid sinus, in a similar location to the occipital sinus previously reported in children. Findings from this study indicated that, as in humans, anatomic variations are common in the intracranial dural venous sinus system of dogs. These anatomic variations should be taken into consideration for surgical planning or diagnosis of cerebrovascular disease. © 2013 Veterinary Radiology & Ultrasound.

Sphenoid sinus types, dimensions and relationship with surrounding structures.

PubMed

Štoković, Nikola; Trkulja, Vladimir; Dumić-Čule, Ivo; Čuković-Bagić, Ivana; Lauc, Tomislav; Vukičević, Slobodan; Grgurević, Lovorka

2016-01-01

The human sphenoid sinus is an extremely variable cavity and an important landmark in hypophyseal surgery. The aim of this study was to investigate the relationship between the sphenoid sinus type, size, extent of pneumatization and occurrence of protrusions of the adjacent neurovascular structures. A total of 51 randomly selected skulls (≥20 years of age, 33 male; 102 sinuses) were analyzed using cone beam computed tomography to estimate pneumatization extension beyond the body of the sphenoid (planum sphenoidale, pterygoid process, greater wings, clivus, dorsum sellae) and protrusions of the maxillary, mandibular, optic or pterygoid nerve or the internal carotid artery. Difference in pneumatization type between the left and the right-sided sinus was observed in 45% of the skulls. Conchal pneumatization was registered in 2%, presellar in 24%, sellar in 41% and postsellar in 33% of total sinuses. Presellar sinuses frequently pneumatized planum sphenoidale and sporadically other structures, and were characterized by sporadic optic nerve protrusions. Sellar and particularly postsellar sinuses were characterized by simultaneous pneumatization extensions and neurovascular protrusions. In the case of postsellar-type sinuses, the probability of these multiple interactions was not affected by their actual size, while it increased with the increasing sinus dimensions in the case of sellar-type sinuses. A more detailed analysis indicated that increasing sinus height, length or width increased the probability of interactions and pneumatization of particular surrounding structures. Data suggest that the sphenoid sinus pneumatization type and dimensions might be used to estimate the risks of iatrogenic injury during transsphenoidal surgical procedures. Copyright © 2015 Elsevier GmbH. All rights reserved.

Prevalence of Sinus Tract in the Patients Visiting Department of Endodontics, Kermanshah School of Dentistry

PubMed Central

Miri, Shima Sadat; Atashbar, Omid; Atashbar, Fardin

2015-01-01

Introduction: Sinus tract is one of the manifestations of chronic dental infections, which is a path for the drainage of the infection and pus. The present study was aimed to investigate the prevalence of sinus tract with dental origin analyze the correlation between sinus tract and related factors. Methods: This study was conducted on 1527 patients, visiting Kermanshah school of dentistry, in 2014.The related teeth were examined in terms of vitality test and exact location of sinus tract. Moreover, the causes of this lesion and the needs for root canal treatment were assessed in these teeth. Having obtained the data from the patients, analyzed by Mann-Whitney, Chi-square tests. Results: The frequency of sinus tract was 9.89% patients. There was a significant correlation between the prevalence of sinus tract and factors such as age, general health status, location of sinus tract and history of root canal treatment. The prevalence of sinus tract in maxilla was higher than the mandible (p=0.087). The prevalence of sinus tract in the posterior teeth (69.54%) was significantly higher than that of anterior teeth (30.46%) (p=0.000). From 724 teeth with periapical inflammation and radiolucency, 9.89% teeth had odontogenic sinus tract, and 23.42% teeth with history of root canal treatment had sinus tract. Conclusions: The most common cause of sinus tract incidence was previous root canal treatment. Therefore, clinicians need to pay a more attention to examining the posterior teeth referred for endodontic treatment. PMID:26153170

Contemporary management of traumatic fractures of the frontal sinus.

PubMed

Guy, W Marshall; Brissett, Anthony E

2013-10-01

This article discusses the classic and contemporary management strategies for treating frontal sinus fractures. The goals of management of frontal sinus fractures are to create a safe sinus by minimizing the likelihood of early and late complications while preserving the function of the sinus and maintaining the cosmetic appearance of the upper face. The assessment and classification of patients with frontal sinus injuries, their management, and the treatment of complications are reviewed. Copyright © 2013 Elsevier Inc. All rights reserved.

Subunit Rotavirus Vaccine Administered Parenterally to Rabbits Induces Active Protective Immunity

PubMed Central

Ciarlet, Max; Crawford, Sue E.; Barone, Christopher; Bertolotti-Ciarlet, Andrea; Ramig, Robert F.; Estes, Mary K.; Conner, Margaret E.

1998-01-01

Virus-like particles (VLPs) are being evaluated as a candidate rotavirus vaccine. The immunogenicity and protective efficacy of different formulations of VLPs administered parenterally to rabbits were tested. Two doses of VLPs (2/6-, G3 2/6/7-, or P[2], G3 2/4/6/7-VLPs) or SA11 simian rotavirus in Freund’s adjuvants, QS-21 (saponin adjuvant), or aluminum phosphate (AlP) were administered. Serological and mucosal immune responses were evaluated in all vaccinated and control rabbits before and after oral challenge with 103 50% infective doses of live P[14], G3 ALA lapine rotavirus. All VLP- and SA11-vaccinated rabbits developed high levels of rotavirus-specific serum and intestinal immunoglobulin G (IgG) antibodies but not intestinal IgA antibodies. SA11 and 2/4/6/7-VLPs afforded similar but much higher mean levels of protection than 2/6/7- or 2/6-VLPs in QS-21. The presence of neutralizing antibodies to VP4 correlated (P < 0.001, r = 0.55; Pearson’s correlation coefficient) with enhanced protection rates, suggesting that these antibodies are important for protection. Although the inclusion of VP4 resulted in higher mean protection levels, high levels of protection (87 to 100%) from infection were observed in individual rabbits immunized with 2/6/7- or 2/6-VLPs in Freund’s adjuvants. Therefore, neither VP7 nor VP4 was absolutely required to achieve protection from infection in the rabbit model when Freund’s adjuvant was used. Our results show that VLPs are immunogenic when administered parenterally to rabbits and that Freund’s adjuvant is a better adjuvant than QS-21. The use of the rabbit model may help further our understanding of the critical rotavirus proteins needed to induce active protection. VLPs are a promising candidate for a parenterally administered subunit rotavirus vaccine. PMID:9765471

Morpho-functional characterization of the systemic venous pole of the reptile heart.

PubMed

Jensen, Bjarke; Vesterskov, Signe; Boukens, Bastiaan J; Nielsen, Jan M; Moorman, Antoon F M; Christoffels, Vincent M; Wang, Tobias

2017-07-27

Mammals evolved from reptile-like ancestors, and while the mammalian heart is driven by a distinct sinus node, a sinus node is not apparent in reptiles. We characterized the myocardial systemic venous pole, the sinus venosus, in reptiles to identify the dominant pacemaker and to assess whether the sinus venosus remodels and adopts an atrium-like phenotype as observed in mammals. Anolis lizards had an extensive sinus venosus of myocardium expressing Tbx18. A small sub-population of cells encircling the sinuatrial junction expressed Isl1, Bmp2, Tbx3, and Hcn4, homologues of genes marking the mammalian sinus node. Electrical mapping showed that hearts of Anolis lizards and Python snakes were driven from the sinuatrial junction. The electrical impulse was delayed between the sinus venosus and the right atrium, allowing the sinus venosus to contract and aid right atrial filling. In proximity of the systemic veins, the Anolis sinus venosus expressed markers of the atrial phenotype Nkx2-5 and Gja5. In conclusion, the reptile heart is driven by a pacemaker region with an expression signature similar to that of the immature sinus node of mammals. Unlike mammals, reptiles maintain a sinuatrial delay of the impulse, allowing the partly atrialized sinus venosus to function as a chamber.

Frontal sinus parameters in computed tomography and sex determination.

PubMed

Akhlaghi, Mitra; Bakhtavar, Khadijeh; Moarefdoost, Jhale; Kamali, Artin; Rafeifar, Shahram

2016-03-01

The frontal sinus is a sturdy part of the skull that is likely to be retrieved for forensic investigations. We evaluated frontal sinus parameters in paranasal sinus computed tomography (CT) images for sex determination. The study was conducted on 200 normal paranasal sinus CT images of 100 men and 100 women of Persian origin. We categorized the studied population into three age groups of 20-34, 35-49 and ⩾ 50 years. The number of partial septa in the right frontal sinus and the maximum height and width were significantly different between the two sexes. The highest precision for sex determination was for the maximum height of the left frontal sinus (61.3%). In the 20-34 years age-group, height and width of the frontal sinus were significantly different between the two sexes and the height of the left sinus had the highest precision (60.8%). In the 35-49 years age-group, right anterior-posterior diameter had a sex determination precision of 52.3%. No frontal sinus parameter reached a statistically significant level for sex determination in the ⩾ 50 years age-group. The number of septa and scallopings were not useful in sex determination. Frontal sinus parameters did not have a high precision in sex determination among Persian adults. Copyright © 2016. Published by Elsevier Ireland Ltd.

Endoscopic agger nasi type Draf IIb treatment for frontal sinus lesions.

PubMed

Shi, Linggai; Liu, Jun; Ma, Jiqing; Liu, Fei; Wang, Guangke

2016-09-01

Treatment of frontal sinus using surgery is complicated owing to the complex anatomical structure of the sinus region. The aim of the present study was to investigate the efficacy and safety of Draf IIb endoscopic frontal sinus surgery treatment for frontal sinus lesions using the agger nasi approach on 19 patients (28 left or and right nasal cavities). A 10-12 mm excision of the upper frontal maxilla was performed for endoscopic resection between the middle turbinate and lateral nasal wall. No serious complications in frontal sinus surgery treatment for the removal of the frontal sinus were observed. Patients were followed up after surgery for 6-36 months. Chronic sinusitis and nasal polyps were identified in 10 cases (19 left or and right nasal cavities; disease control, 15 left or and right nasal cavities; and disease partial control, 4 left or and right nasal cavities). Frontal sinus inverted papilloma was observed in 9 cases (9 left or and right nasal cavities). Frontal sinus inverted papilloma were successfully treated in 8 cases, and 1 case of recurrence was observed. In conclusion, the nasal endoscopic Draf IIb agger nasi approach is a minimally invasive treatment for frontal sinus lesions. This surgical procedure is safe and less complicated and may be applied in the clinic.

The relationship between frontal sinus morphology and skeletal maturation.

PubMed

Buyuk, Suleyman Kutalmıs; Simsek, Huseyin; Karaman, Ahmet

2018-01-03

The aim of this study is to evaluate the relationship between frontal sinus morphology and hand-wrist bone maturation by using postero-anterior (PA) cephalometric radiographs. The study sample consisted of 220 patients divided into eleven groups based on the hand-wrist radiographs. The right and left maximum height, width and area of the frontal sinus parameters were measured in postero-anterior cephalometric radiographs 220 subjects aged 8-18 years. The hand-wrist skeletal maturation stages were evaluated on the hand-wrist radiographs using the method of Fishman. The Kendall tau-b values were analyzed to evaluate the correlation between the hand-wrist skeletal maturation stages and the frontal sinus parameters. The right and left frontal sinus areas and widths were found to be larger in males than in females (p < 0.05). In males, a significant difference was observed in all frontal sinus parameters in different maturation stages (p < 0.001), while a statistically significant correlation was found in females between the left frontal sinus area, right frontal sinus height, right frontal sinus width and different maturation stages (p < 0.05). In conclusion, the relationship between frontal sinus dimensions obtained from PA cephalometric radiographs and hand-wrist maturation stages suggests that frontal sinuses can be used in determining growth and development.

Biodegradable chitosan and polylactic acid-based intraocular micro-implant for sustained release of methotrexate into vitreous: analysis of pharmacokinetics and toxicity in rabbit eyes.

PubMed

Manna, Soumyarwit; Banerjee, Rupak K; Augsburger, James J; Al-Rjoub, Marwan F; Donnell, Anna; Correa, Zelia M

2015-08-01

The purpose of this study was to evaluate the pharmacokinetics and toxicity of a chitosan (CS) and polylactic acid (PLA) based methotrexate (MTX) intravitreal micro-implant in an animal model using rabbit eyes. CS- and PLA-based micro-implants containing 400 μg of MTX were fabricated using lyophilization and dip-coating techniques. The micro-implants were surgically implanted in the vitreous of eight New Zealand rabbits employing minimally invasive technique. The PLA-coated CS-MTX micro-implant was inserted in the right eye and the placebo micro-implant in the left eye of each rabbit. Two rabbits were euthanized at each pre-determined time point post-implantation (days 5, 12, 19, and 33) for pharmacokinetics and histopathology evaluation. A therapeutic concentration of MTX (0.1-1.0 μM) in the vitreous was detected in the rabbit eyes studied for 33 days. The MTX release from the coated micro-implants followed a first order kinetics (R (2) ~ 0.88), implying that MTX release depends on the concentration of MTX in the micro-implant. Histopathological analysis of the enucleated eyes failed to show any signs of infection or tissue toxicity in any of the specimens. The PLA-coated CS-MTX micro-implants were able to deliver therapeutic release of MTX for a period of more than 1 month without detectable toxicity in a rabbit model. The micro-implants can be further investigated as a prospective alternative to current treatment protocols of repeated intravitreal MTX injections in intraocular disorders such as primary intraocular lymphoma, and selected cases of non-microbial intraocular inflammation.

A novel method for blood volume estimation using trivalent chromium in rabbit models.

PubMed

Baby, Prathap Moothamadathil; Kumar, Pramod; Kumar, Rajesh; Jacob, Sanu S; Rawat, Dinesh; Binu, V S; Karun, Kalesh M

2014-05-01

Blood volume measurement though important in management of critically ill-patients is not routinely estimated in clinical practice owing to labour intensive, intricate and time consuming nature of existing methods. The aim was to compare blood volume estimations using trivalent chromium [(51)Cr(III)] and standard Evans blue dye (EBD) method in New Zealand white rabbit models and establish correction-factor (CF). Blood volume estimation in 33 rabbits was carried out using EBD method and concentration determined using spectrophotometric assay followed by blood volume estimation using direct injection of (51)Cr(III). Twenty out of 33 rabbits were used to find CF by dividing blood volume estimation using EBD with blood volume estimation using (51)Cr(III). CF is validated in 13 rabbits by multiplying it with blood volume estimation values obtained using (51)Cr(III). The mean circulating blood volume of 33 rabbits using EBD was 142.02 ± 22.77 ml or 65.76 ± 9.31 ml/kg and using (51)Cr(III) was estimated to be 195.66 ± 47.30 ml or 89.81 ± 17.88 ml/kg. The CF was found to be 0.77. The mean blood volume of 13 rabbits measured using EBD was 139.54 ± 27.19 ml or 66.33 ± 8.26 ml/kg and using (51)Cr(III) with CF was 152.73 ± 46.25 ml or 71.87 ± 13.81 ml/kg (P = 0.11). The estimation of blood volume using (51)Cr(III) was comparable to standard EBD method using CF. With further research in this direction, we envisage human blood volume estimation using (51)Cr(III) to find its application in acute clinical settings.

Effects of sinus surgery in patients with cystic fibrosis after lung transplantation: a 10-year experience.

PubMed

Holzmann, David; Speich, Rudolf; Kaufmann, Thomas; Laube, Irene; Russi, Erich W; Simmen, Daniel; Weder, Walter; Boehler, Annette

2004-01-15

Chronic infectious rhinosinusitis with Pseudomonas aeruginosa is common in cystic fibrosis and may result in allograft infection after lung transplantation. Sinus surgery followed by nasal care may reduce these adverse effects. Sinus surgery was performed in 37 patients with cystic fibrosis after transplantation. Bacteriology of sinus aspirates (n=771) and bronchoalveolar lavage (BAL) (n=256) was correlated with clinical data. Sinus surgery was successful in 54% and partially successful in 27% of patients. A significant correlation between negative sinus aspirates and negative BAL and between positive sinus aspirates and positive BAL (P<0.0001) was found. Successful sinus management led to a lower incidence of tracheobronchitis and pneumonia (P=0.009) and a trend toward a lower incidence of bronchiolitis obliterans syndrome (P=0.23). Sinus surgery followed by daily nasal douching may control posttransplant lower airway colonization and infection. In the long term, this concept may lead to less bronchiolitis obliterans syndrome by decreasing bronchiolar inflammation.

Impact of a Novel, Anti-microbial Dressing on In Vivo, Pseudomonas aeruginosa Wound Biofilm: Quantitative Comparative Analysis using a Rabbit Ear Model

DTIC Science & Technology

2014-12-01

previously pub- lished in vivo, wound biofilm model.19 Rabbits were anesthe- tized with intramuscular injection of a ketamine (22.5 mg/kg) and xylazine (3.5...22: 12–16. 3. Krasner D. Painful venous ulcers: themes and stories about their impact on quality of life. Ostomy Wound Manage 1998; 44: 38–49. 4

A laboratory model of the aortic root flow including the coronary arteries

NASA Astrophysics Data System (ADS)

Querzoli, Giorgio; Fortini, Stefania; Espa, Stefania; Melchionna, Simone

2016-08-01

Cardiovascular flows have been extensively investigated by means of in vitro models to assess the prosthetic valve performances and to provide insight into the fluid dynamics of the heart and proximal aorta. In particular, the models for the study of the flow past the aortic valve have been continuously improved by including, among other things, the compliance of the vessel and more realistic geometries. The flow within the sinuses of Valsalva is known to play a fundamental role in the dynamics of the aortic valve since they host a recirculation region that interacts with the leaflets. The coronary arteries originate from the ostia located within two of the three sinuses, and their presence may significantly affect the fluid dynamics of the aortic root. In spite of their importance, to the extent of the authors' knowledge, coronary arteries were not included so far when modeling in vitro the transvalvular aortic flow. We present a pulse duplicator consisting of a passively pulsing ventricle, a compliant proximal aorta, and coronary arteries connected to the sinuses of Valsalva. The coronary flow is modulated by a self-regulating device mimicking the physiological mechanism, which is based on the contraction and relaxation of the heart muscle during the cardiac cycle. Results show that the model reproduces satisfyingly the coronary flow. The analysis of the time evolution of the velocity and vorticity fields within the aortic root reveals the main characteristics of the backflow generated through the aorta in order to feed the coronaries during the diastole. Experiments without coronary flow have been run for comparison. Interestingly, the lifetime of the vortex forming in the sinus of Valsalva during the systole is reduced by the presence of the coronaries. As a matter of fact, at the end of the systole, that vortex is washed out because of the suction generated by the coronary flow. Correspondingly, the valve closure is delayed and faster compared to the case with no coronary flow.

3D Rapid Prototyping for Otolaryngology-Head and Neck Surgery: Applications in Image-Guidance, Surgical Simulation and Patient-Specific Modeling.

PubMed

Chan, Harley H L; Siewerdsen, Jeffrey H; Vescan, Allan; Daly, Michael J; Prisman, Eitan; Irish, Jonathan C

2015-01-01

The aim of this study was to demonstrate the role of advanced fabrication technology across a broad spectrum of head and neck surgical procedures, including applications in endoscopic sinus surgery, skull base surgery, and maxillofacial reconstruction. The initial case studies demonstrated three applications of rapid prototyping technology are in head and neck surgery: i) a mono-material paranasal sinus phantom for endoscopy training ii) a multi-material skull base simulator and iii) 3D patient-specific mandible templates. Digital processing of these phantoms is based on real patient or cadaveric 3D images such as CT or MRI data. Three endoscopic sinus surgeons examined the realism of the endoscopist training phantom. One experienced endoscopic skull base surgeon conducted advanced sinus procedures on the high-fidelity multi-material skull base simulator. Ten patients participated in a prospective clinical study examining patient-specific modeling for mandibular reconstructive surgery. Qualitative feedback to assess the realism of the endoscopy training phantom and high-fidelity multi-material phantom was acquired. Conformance comparisons using assessments from the blinded reconstructive surgeons measured the geometric performance between intra-operative and pre-operative reconstruction mandible plates. Both the endoscopy training phantom and the high-fidelity multi-material phantom received positive feedback on the realistic structure of the phantom models. Results suggested further improvement on the soft tissue structure of the phantom models is necessary. In the patient-specific mandible template study, the pre-operative plates were judged by two blinded surgeons as providing optimal conformance in 7 out of 10 cases. No statistical differences were found in plate fabrication time and conformance, with pre-operative plating providing the advantage of reducing time spent in the operation room. The applicability of common model design and fabrication techniques across a variety of otolaryngological sub-specialties suggests an emerging role for rapid prototyping technology in surgical education, procedure simulation, and clinical practice.

3D Rapid Prototyping for Otolaryngology—Head and Neck Surgery: Applications in Image-Guidance, Surgical Simulation and Patient-Specific Modeling

PubMed Central

Chan, Harley H. L.; Siewerdsen, Jeffrey H.; Vescan, Allan; Daly, Michael J.; Prisman, Eitan; Irish, Jonathan C.

2015-01-01

The aim of this study was to demonstrate the role of advanced fabrication technology across a broad spectrum of head and neck surgical procedures, including applications in endoscopic sinus surgery, skull base surgery, and maxillofacial reconstruction. The initial case studies demonstrated three applications of rapid prototyping technology are in head and neck surgery: i) a mono-material paranasal sinus phantom for endoscopy training ii) a multi-material skull base simulator and iii) 3D patient-specific mandible templates. Digital processing of these phantoms is based on real patient or cadaveric 3D images such as CT or MRI data. Three endoscopic sinus surgeons examined the realism of the endoscopist training phantom. One experienced endoscopic skull base surgeon conducted advanced sinus procedures on the high-fidelity multi-material skull base simulator. Ten patients participated in a prospective clinical study examining patient-specific modeling for mandibular reconstructive surgery. Qualitative feedback to assess the realism of the endoscopy training phantom and high-fidelity multi-material phantom was acquired. Conformance comparisons using assessments from the blinded reconstructive surgeons measured the geometric performance between intra-operative and pre-operative reconstruction mandible plates. Both the endoscopy training phantom and the high-fidelity multi-material phantom received positive feedback on the realistic structure of the phantom models. Results suggested further improvement on the soft tissue structure of the phantom models is necessary. In the patient-specific mandible template study, the pre-operative plates were judged by two blinded surgeons as providing optimal conformance in 7 out of 10 cases. No statistical differences were found in plate fabrication time and conformance, with pre-operative plating providing the advantage of reducing time spent in the operation room. The applicability of common model design and fabrication techniques across a variety of otolaryngological sub-specialties suggests an emerging role for rapid prototyping technology in surgical education, procedure simulation, and clinical practice. PMID:26331717

Identification and characterization of a Na+-dependent neutral amino acid transporter, ASCT1, in rabbit corneal epithelial cell culture and rabbit cornea.

PubMed

Katragadda, Suresh; Talluri, Ravi Sankar; Pal, Dhananjay; Mitra, Ashim K

2005-11-01

The aim of this study was to investigate the presence of a Na+-dependent neutral amino acid transporter, ASCT1, in rabbit primary corneal epithelial cell culture and rabbit cornea. Uptake studies were carried out on rabbit primary corneal epithelial culture (rPCEC) cells using 12-well plates. Transport studies were conducted with isolated rabbit corneas at 34 degrees C. Uptake and transport of L-alanine was determined at various concentrations. Inhibition studies were conducted in presence of various L- and D-amino acids, metabolic inhibitors like ouabain and sodium azide, and in the absence of sodium to delineate the functional characteristics of L-alanine uptake and transport. Reverse transcription-polymerase chain reaction (RT-PCR) was performed on total RNA harvested from rabbit cornea and rPCEC cells for identification of ASCT1. Uptake of L-Ala was found to be saturable with a Km of 0.71 mM and a Vmax value of 0.84 micromoles min(-1) mg(-1) protein. Uptake was independent of pH and energy but depends on sodium. It was inhibited by serine, threonine, cysteine, and glutamine but did not respond to BCH (2-aminobicyclo [2,2,1] heptane-2-carboxylic acid) and MeAIB (alpha -methylaminoisobutyric acid). Transport of L-Ala across rabbit cornea was also saturable (Km 6.52 mM and Vmax 1.09 x 10(-2) micromoles min(-1) cm(-2)), energy independent, and subject to similar competitive inhibition. Presence of ASCT1 on rPCEC and on rabbit cornea was identified by RT-PCR. L-Alanine, the chosen model substrate, was actively transported by Na+-dependent, neutral amino acid exchanger ASCT1, which was identified and functionally characterized on rPCEC cells and rabbit cornea.

Induced Autologous Stem Cell Transplantation for Treatment of Rabbit Renal Interstitial Fibrosis

PubMed Central

Ruan, Guang-Ping; Xu, Fan; Li, Zi-An; Zhu, Guang-Xu; Pang, Rong-Qing; Wang, Jin-Xiang; Cai, Xue-Min; He, Jie; Yao, Xiang; Ruan, Guang-Hong; Xu, Xin-Ming; Pan, Xing-Hua

2013-01-01

Introduction Renal interstitial fibrosis (RIF) is a significant cause of end-stage renal failure. The goal of this study was to characterize the distribution of transplanted induced autologous stem cells in a rabbit model of renal interstitial fibrosis and evaluate its therapeutic efficacy for treatment of renal interstitial fibrosis. Methods A rabbit model of renal interstitial fibrosis was established. Autologous fibroblasts were cultured, induced and labeled with green fluorescent protein (GFP). These labeled stem cells were transplanted into the renal artery of model animals at 8 weeks. Results Eight weeks following transplantation of induced autologous stem cells, significant reductions (P < 0.05) were observed in serum creatinine (SCr) (14.8 ± 1.9 mmol/L to 10.1 ± 2.1 mmol/L) and blood urea nitrogen (BUN) (119 ± 22 µmol/L to 97 ± 13 µmol/L), indicating improvement in renal function. Conclusions We successfully established a rabbit model of renal interstitial fibrosis and demonstrated that transplantation of induced autologous stem cells can repair kidney damage within 8 weeks. The repair occurred by both inhibition of further development of renal interstitial fibrosis and partial reversal of pre-existing renal interstitial fibrosis. These beneficial effects lead to the development of normal tissue structure and improved renal function. PMID:24367598

Anthrax vaccine antigen-adjuvant formulations completely protect New Zealand white rabbits against challenge with Bacillus anthracis Ames strain spores.

PubMed

Peachman, Kristina K; Li, Qin; Matyas, Gary R; Shivachandra, Sathish B; Lovchik, Julie; Lyons, Rick C; Alving, Carl R; Rao, Venigalla B; Rao, Mangala

2012-01-01

In an effort to develop an improved anthrax vaccine that shows high potency, five different anthrax protective antigen (PA)-adjuvant vaccine formulations that were previously found to be efficacious in a nonhuman primate model were evaluated for their efficacy in a rabbit pulmonary challenge model using Bacillus anthracis Ames strain spores. The vaccine formulations include PA adsorbed to Alhydrogel, PA encapsulated in liposomes containing monophosphoryl lipid A, stable liposomal PA oil-in-water emulsion, PA displayed on bacteriophage T4 by the intramuscular route, and PA mixed with Escherichia coli heat-labile enterotoxin administered by the needle-free transcutaneous route. Three of the vaccine formulations administered by the intramuscular or the transcutaneous route as a three-dose regimen induced 100% protection in the rabbit model. One of the formulations, liposomal PA, also induced significantly higher lethal toxin neutralizing antibodies than PA-Alhydrogel. Even 5 months after the second immunization of a two-dose regimen, rabbits vaccinated with liposomal PA were 100% protected from lethal challenge with Ames strain spores. In summary, the needle-free skin delivery and liposomal formulation that were found to be effective in two different animal model systems appear to be promising candidates for next-generation anthrax vaccine development.

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.

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 Safety Study on Intrathecal Delivery of Autologous Mesenchymal Stromal Cells in Rabbits Directly Supporting Phase I Human Trials

PubMed Central

Chen, Bingkun K.; Staff, Nathan P.; Knight, Andrew M.; Nesbitt, Jarred J.; Butler, Greg W.; Padley, Douglas J.; Parisi, Joseph E.; Dietz, Allan B.; Windebank, Anthony J.

2014-01-01

Background There are no effective treatments that slow the progression of neurodegenerative diseases. A major challenge of treatment in neurodegenerative diseases is appropriate delivery of pharmaceuticals into the cerebrospinal fluid (CSF) of affected individuals. Mesenchymal stromal cells (MSCs – either naïve or modified) are a promising therapy in neurodegenerative diseases and may be delivered directly into the CSF where they can reside for months. In this preclinical study, we evaluated the safety of intrathecal autologous MSCs in a rabbit model. Methods Autologous adipose-derived MSCs (or a-CSF) were delivered intrathecally, either with single or repeated injections into the foramen magnum of healthy rabbits, and monitored for 4 and 12 weeks, respectively. Results Rabbits tolerated injections well and no definitive MSC-related side effects were observed apart from three rabbits that had delayed death secondary to traumatic foramen magnum puncture. Functional assessments and body weights were equivalent between groups. Gross pathology and histology did not reveal any abnormalities or tumor growth. Complete blood count (CBC) data were normal and there were no differences in CSF IL-6 levels in all groups tested. Discussion Our data suggest that intrathecal delivery of autologous MSCs is safe in a rabbit model. Data from this study has supported two successful Investigational New Drug (IND) applications to the FDA, resulting in the initiation of two clinical trials using autologous MSCs in amyotrophic lateral sclerosis and multiple system atrophy. PMID:25413276

Magnetic resonance imaging and computational fluid dynamics (CFD) simulations of rabbit nasal airflows for the development of hybrid CFD/PBPK models.

PubMed

Corley, R A; Minard, K R; Kabilan, S; Einstein, D R; Kuprat, A P; Harkema, J R; Kimbell, J S; Gargas, M L; Kinzell, John H

2009-05-01

The percentages of total airflows over the nasal respiratory and olfactory epithelium of female rabbits were calculated from computational fluid dynamics (CFD) simulations of steady-state inhalation. These airflow calculations, along with nasal airway geometry determinations, are critical parameters for hybrid CFD/physiologically based pharmacokinetic models that describe the nasal dosimetry of water-soluble or reactive gases and vapors in rabbits. CFD simulations were based upon three-dimensional computational meshes derived from magnetic resonance images of three adult female New Zealand White (NZW) rabbits. In the anterior portion of the nose, the maxillary turbinates of rabbits are considerably more complex than comparable regions in rats, mice, monkeys, or humans. This leads to a greater surface area to volume ratio in this region and thus the potential for increased extraction of water soluble or reactive gases and vapors in the anterior portion of the nose compared to many other species. Although there was considerable interanimal variability in the fine structures of the nasal turbinates and airflows in the anterior portions of the nose, there was remarkable consistency between rabbits in the percentage of total inspired airflows that reached the ethmoid turbinate region (approximately 50%) that is presumably lined with olfactory epithelium. These latter results (airflows reaching the ethmoid turbinate region) were higher than previous published estimates for the male F344 rat (19%) and human (7%). These differences in regional airflows can have significant implications in interspecies extrapolations of nasal dosimetry.

Non-invasive evaluation of liver stiffness after splenectomy in rabbits with CCl4-induced liver fibrosis

PubMed Central

Wang, Ming-Jun; Ling, Wen-Wu; Wang, Hong; Meng, Ling-Wei; Cai, He; Peng, Bing

2016-01-01

AIM To investigate the diagnostic performance of liver stiffness measurement (LSM) by elastography point quantification (ElastPQ) in animal models and determine the longitudinal changes in liver stiffness by ElastPQ after splenectomy at different stages of fibrosis. METHODS Liver stiffness was measured in sixty-eight rabbits with CCl4-induced liver fibrosis at different stages and eight healthy control rabbits by ElastPQ. Liver biopsies and blood samples were obtained at scheduled time points to assess liver function and degree of fibrosis. Thirty-one rabbits with complete data that underwent splenectomy at different stages of liver fibrosis were then included for dynamic monitoring of changes in liver stiffness by ElastPQ and liver function according to blood tests. RESULTS LSM by ElastPQ was significantly correlated with histologic fibrosis stage (r = 0.85, P < 0.001). The optimal cutoff values by ElastPQ were 11.27, 14.89, and 18.21 kPa for predicting minimal fibrosis, moderate fibrosis, and cirrhosis, respectively. Longitudinal monitoring of the changes in liver stiffness by ElastPQ showed that early splenectomy (especially F1) may delay liver fibrosis progression. CONCLUSION ElastPQ is an available, convenient, objective and non-invasive technique for assessing liver stiffness in rabbits with CCl4-induced liver fibrosis. In addition, liver stiffness measurements using ElastPQ can dynamically monitor the changes in liver stiffness in rabbit models, and in patients, after splenectomy. PMID:28028365

Pneumonic Tularemia in Rabbits Resembles the Human Disease as Illustrated by Radiographic and Hematological Changes after Infection

PubMed Central

Reed, Douglas S.; Smith, Le'Kneitah; Dunsmore, Tammy; Trichel, Anita; Ortiz, Luis A.; Cole, Kelly Stefano; Barry, Eileen

2011-01-01

Background Pneumonic tularemia is caused by inhalation of the gram negative bacterium, Francisella tularensis. Because of concerns that tularemia could be used as a bioterrorism agent, vaccines and therapeutics are urgently needed. Animal models of pneumonic tularemia with a pathophysiology similar to the human disease are needed to evaluate the efficacy of these potential medical countermeasures. Principal Findings Rabbits exposed to aerosols containing Francisella tularensis strain SCHU S4 developed a rapidly progressive fatal pneumonic disease. Clinical signs became evident on the third day after exposure with development of a fever (>40.5°C) and a sharp decline in both food and water intake. Blood samples collected on day 4 found lymphopenia and a decrease in platelet counts coupled with elevations in erythrocyte sedimentation rate, alanine aminotransferase, cholesterol, granulocytes and monocytes. Radiographs demonstrated the development of pneumonia and abnormalities of intestinal gas consistent with ileus. On average, rabbits were moribund 5.1 days after exposure; no rabbits survived exposure at any dose (190–54,000 cfu). Gross evaluation of tissues taken at necropsy showed evidence of pathology in the lungs, spleen, liver, kidney and intestines. Bacterial counts confirmed bacterial dissemination from the lungs to the liver and spleen. Conclusions/Significance The pathophysiology of pneumonic tularemia in rabbits resembles what has been reported for humans. Rabbits therefore are a relevant model of the human disease caused by type A strains of F. tularensis. PMID:21931798

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.

Topographic anatomy of the fetal inferior vena cava, coronary sinus, and pulmonary veins: Variations in Chiari's network.

PubMed

Naito, Michiko; Yu, Hee Chul; Kim, Ji Hyun; Rodríguez-Vázquez, José Francisco; Murakami, Gen; Cho, Baik Hwan

2015-07-01

To understand anomalies in Chiari's network better, we assessed the topographical anatomy of the fetal inferior vena cava (IVC), coronary sinus, and atria. We examined sagittal serial paraffin sections of 15 human fetuses of crown-rump length 24-36 mm, corresponding to a gestational age of 8 weeks. Although their outflow tract morphologies were similar, these 15 specimens could be classified into two groups. In eight specimens, the left common cardinal vein reached the body wall, whereas in the other seven the vein was obliterated near the left pulmonary vein. Irrespective of the group in which the specimen was included, the anteroposterior arrangement of the coronary sinus, the sinus septum (septum), and the right sinus valve (right valve) could be classified into three types: the right valve-septum-coronary sinus arrangement in seven specimens; the right valve-coronary sinus-septum arrangement in five; and the coronary sinus-right valve-septum arrangement in three. Depending on differences in topographical anatomy, the sinus septum separated the coronary sinus opening from either the right or the left atrium. Likewise, the coronary sinus opening was either adjacent to or distant from the IVC terminal. Rather than the counter-side position of the right valve being at the IVC terminal, the left sinus valve protruded leftward, forming an incomplete interatrial septum. Fetal variations seemed to be closely connected with individual variations and a high frequency of Chiari's network anomalies in adults. © 2014 Wiley Periodicals, Inc.

Effects of sinus surgery on lung transplantation outcomes in cystic fibrosis.

PubMed

Leung, Man-Kit; Rachakonda, Leelanand; Weill, David; Hwang, Peter H

2008-01-01

In cystic fibrosis (CF) patients who are candidates for lung transplant, pretransplant sinus surgery has been advocated to avoid bacterial seeding of the transplanted lungs. This study reviews the 17-year experience of pretransplant sinus surgery among CF patients at a major transplant center. Retrospective chart review was performed in all CF patients who underwent heart-lung or lung transplantation at Stanford Medical Center between 1988 and 2005. Postoperative culture data from bronchoalveolar lavage (BAL) and sinus aspirates were evaluated, in addition to survival data. Eighty-seven CF transplant recipients underwent pretransplant sinus surgery; 87% (n=59/68) of patients showed recolonization of the lung grafts with Pseudomonas on BAL cultures. The median postoperative time to recolonization was 19 days. Bacterial floras cultured from sinuses were similar in type and prevalence as the floras cultured from BAL. When compared with published series of comparable cohorts in which pretransplant sinus surgery was not performed, there was no statistically significant difference in the prevalence of Pseudomonas recolonization. Times to recolonization also were similar. Survival rates in our cohort were similar to national survival rates for CF lung transplant recipients. Despite pretransplant sinus surgery, recolonization of lung grafts occurs commonly and rapidly with a spectrum of flora that mimics the sinus flora. Survival rates of CF patients who undergo prophylactic sinus surgery are similar to those from centers where prophylactic sinus surgery is not performed routinely. Pretransplant sinus surgery does not appear to prevent lung graft recolonization and is not associated with overall survival benefit.

[Investigation of fat in the dural sinus].

PubMed

Tokiguchi, S

1991-08-25

Detection of fat in the cranium usually indicates the presence of a fat-containing tumor such as lipoma, dermoid cyst or teratoma. However, since 1982, Hasso et al demonstrated with CT the presence of normal adipose tissue in the cavernous sinus, the mere existence of fat in the cranium does not necessarily mean the presence of a fatty tumor. The author first described fat deposition in the superior sagittal sinus and torcular Herophili following a CT study performed in 1986. The purpose of this study was to investigate the distribution, frequency, and anatomical correlations of fat in the dural sinus as demonstrated on CT. Fat was detected in the cavernous sinus in 20% of all cases (492/2408), and occurred more frequently (25%) in those older than 50 years. Fat was less frequent in the other dural sinuses (3%; 75/2296). The most common location was the torcular Herophili, followed in decreasing order of frequency by the straight sinus, inferior sagittal sinus, superior sagittal sinus and transverse sinus. Pathological examination was performed in three cases. Fat deposition was composed of normal adipose tissue and was devoid of fibrous encapsulation or infiltration. In one case, the fat seemed to be partly exposed to the subarachnoid space on CT, whereas on autopsy, thin dura mater covering the fat nodule was confirmed. Fat in the dural sinus must be differentiated from cavernous nodule or sinus thrombosis. The Hounsfield unit may be helpful in making a definitive diagnosis.

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

PubMed Central

2012-01-01

Background Inhibitors of pancreatic alpha-amylase are potential drugs to treat diabetes and obesity. In order to find compounds that would be effective amylase inhibitors, in vitro and in vivo models are usually used. The accuracy of models is limited, but these tools are nonetheless valuable. In vitro models could be used in large screenings involving thousands of chemicals that are tested to find potential lead compounds. In vivo models are still used as preliminary mean of testing compounds behavior in the whole organism. In the case of alpha-amylase inhibitors, both rats and rabbits could be chosen as in vivo models. The question was which animal could present more accuracy with regard to its pancreatic alpha-amylase. Results As there is no crystal structure of these enzymes, a molecular modeling study was done in order to compare the rabbit and rat enzymes with the human one. The overall result is that rabbit enzyme could probably be a better choice in this regard, but in the case of large ligands, which could make putative interactions with the −4 subsite of pancreatic alpha-amylase, interpretation of results should be made cautiously. Conclusion Molecular modeling tools could be used to choose the most suitable model enzyme that would help to identify new enzyme inhibitors. In the case of alpha-amylase, three-dimensional structures of animal enzymes show differences with the human one which should be taken into account when testing potential new drugs. PMID:23352052

Mechanism - based translational pharmacokinetic - pharmacodynamic model to predict intraocular pressure lowering effect of drugs in patients with glaucoma or ocular hypertension.

PubMed

Durairaj, Chandrasekar; Shen, Jie; Cherukury, Madhu

2014-08-01

To develop a mechanism based translational pharmacokinetic-pharmacodynamic (PKPD) model in preclinical species and to predict the intraocular pressure (IOP) following drug treatment in patients with glaucoma or ocular hypertension (OHT). Baseline diurnal IOP of normotensive albino rabbits, beagle dogs and patients with glaucoma or OHT was collected from literature. In addition, diurnal IOP of patients treated with brimonidine or Xalatan® were also obtained from literature. Healthy normotensive New Zealand rabbits were topically treated with a single drop of 0.15% brimonidine tartrate and normotensive beagle dogs were treated with a single drop of Xalatan®. At pre-determined time intervals, IOP was measured and aqueous humor samples were obtained from a satellite group of animals. Population based PKPD modeling was performed to describe the IOP data and the chosen model was extended to predict the IOP in patients. Baseline IOP clearly depicts a distinctive circadian rhythm in rabbits versus human. An aqueous humor dynamics based physiological model was developed to describe the baseline diurnal IOP across species. Model was extended to incorporate the effect of drug administration on baseline IOP in rabbits and dogs. The translational model with substituted human aqueous humor dynamic parameters predicted IOP in patients following drug treatment. A physiology based mechanistic PKPD model was developed to describe the baseline and post-treatment IOP in animals. The preclinical PKPD model was successfully translated to predict IOP in patients with glaucoma or OHT and can be applied in assisting dose and treatment selection and predicting outcome of glaucoma clinical trials.

A comparative study of the effect of Bio-Oss® in combination with concentrated growth factors or bone marrow-derived mesenchymal stem cells in canine sinus grafting.

PubMed

Wang, Fang; Li, Qiong; Wang, Zuolin

2017-08-01

To compare the effects of Bio-Oss ® in combination with concentrated growth factors (CGFs) and bone marrow-derived mesenchymal stem cells (BMSCs) on bone regeneration for maxillary sinus floor augmentation in beagle dogs. Six beagle dogs received bilateral maxillary sinus floor augmentation. Venous blood drawn from dogs was collected and centrifuged to obtain CGFs. BMSCs derived from canine bone marrow were cultured using density gradient centrifugation. The suspension of BMSCs was added onto Bio-Oss ® granules at a density of 2 × 10 6 cells/ml, and the BMSCs/Bio-Oss ® constructs were incubated for an additional 4 h before use. Twelve sinuses were grafted with a mixture of CGFs/Bio-Oss ® , BMSCs/Bio-Oss ® construct, or Bio-Oss ® alone. Six months later, the bone formation of bilateral sinuses was evaluated by Micro-CT, microhardness test, histological examination, and histomorphometry. No adverse effect was found in these dogs. The dome-shaped augmentation protruded into the sinus cavity. Micro-CT revealed that there was significant difference in BV/TV but not in Tb. N, between groups A, B, and C. The extent of microhardness in groups A and B was significantly higher than in group C. The proportion of newly formed bone in groups A and B showed significant difference when compared to group C (P ≤ 0.01). The amount of residual grafts in groups A and B was significantly lower than in group C. Grafting with Bio-Oss ® in combination with CGFs can increase new bone formation more efficiently than using Bio-Oss ® alone in a canine model. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Inhibition of cartilage degradation and suppression of PGE2 and MMPs expression by Pomegranate Fruit Extract in a model of Post-Traumatic Osteoarthritis

PubMed Central

Akhtar, Nahid; Khan, Nazir M.; Ashruf, Omer; Haqqi, Tariq M.

2016-01-01

Background Osteoarthritis (OA) is characterized by cartilage degradation in the affected joints. Pomegranate fruit extract (PFE) inhibits cartilage degradation in vitro. Here we determined whether oral consumption of PFE inhibits disease progression in rabbits with surgically-induced OA. Methods OA was surgically induced in the tibiofemoral joints of adult NZW rabbits. In one group animals were fed PFE in water for 8 weeks post-surgery. In the second group, animals were fed PFE for 2 weeks before surgery andfor 8 weeks post-surgery.Histological assessment and scoring of the cartilage was per OARSI guidelines. Gene expression and MMPs activity were determined using qRT-PCR and fluorometric assay, respectively. IL-1β, MMP-13, IL-6, PGE2 and COL2A1 levels in synovial fluid/plasma/culture mediawere quantified using ELISA. Expression of active Caspase-3 and PARP p85 was determined by immunohistochemistry. Effect of PFE and inhibitors of MMP-13, MAPK and NF-κB was studied in IL-1β-stimulated rabbit articular chondrocytes. Results Safranin-O-staining and chondrocyte cluster formation was significantly reduced in the ACLT+PFE fed groups. Expression of MMP-3, MMP-9 and MMP-13 mRNAwas higher in the cartilage of rabbits given water alone but was significantly lower in the animals fed PFE. PFE-fed rabbits had lowerIL-6, MMP-13 and PGE2 levels in the synovial fluid and plasma respectively and showed higher expression of ACAN and COL2A1 mRNA. Significantly higher numbers of chondrocytes were positive for markers of apoptosisin the joints of rabbits with OA given water only compared to rabbits in the PFE-fed groups. PFE pretreatment significantly reduced IL-1β induced IL-6 and MMPs expression in rabbit articular chondrocytes. These effects were also mimicked using MMP-13, MAPK and NF-κB inhibitors in IL-1β-stimulated rabbit chondrocytes. In an in vitro activity assay, PFE blocked the activity of MMP-13.Like MAPK and NF-κB inhibitors, PFE was also effective in inhibiting IL-1β-induced PGE2 production in rabbit chondrocytes. PFE also reversed the inhibitory effect of IL-1β on COL2A1 mRNA and protein expression in IL-1β-stimulated rabbit chondrocytes. Conclusion Our data highlighted the chondroprotective effects of PFE oral consumption in a model of post-traumatic OA and suggests that PFE derived compounds may have potential value in the management of OA. PMID:27908544

Particle Image Velocimetry studies of bicuspid aortic valve hemodynamics

NASA Astrophysics Data System (ADS)

Saikrishnan, Neelakantan; Yap, Choon-Hwai; Yoganathan, Ajit P.

2010-11-01

Bicuspid aortic valves (BAVs) are a congenital anomaly of the aortic valve with two fused leaflets, affecting about 1-2% of the population. BAV patients have much higher incidence of valve calcification & aortic dilatation, which may be related to altered mechanical forces from BAV hemodynamics. This study aims to characterize BAV hemodynamics using Particle Image Velocimetry(PIV). BAV models are constructed from normal explanted porcine aortic valves by suturing two leaflets together. The valves are mounted in an acrylic chamber with two sinuses & tested in a pulsatile flow loop at physiological conditions. 2D PIV is performed to obtain flow fields in three planes downstream of the valve. The stenosed BAV causes an eccentric jet, resulting in a very strong vortex in the normal sinus. The bicuspid sinus vortex appears much weaker, but more unstable. Unsteady oscillatory shear stresses are also observed, which have been associated with adverse biological response; characterization of the hemodynamics of BAVs will provide the first step to understanding these processes better. Results from multiple BAV models of varying levels of stenosis will be presented & higher stenosis corresponded to stronger jets & increased aortic wall shear stresses.

Cardiac regulation in the socially monogamous prairie vole

PubMed Central

Grippo, Angela J.; Lamb, Damon G.; Carter, C. Sue; Porges, Stephen W.

2007-01-01

Social experiences, both positive and negative, may influence cardiovascular regulation. Prairie voles (Microtus ochrogaster) are socially monogamous rodents that form social bonds similar to those seen in primates, and this species may provide a useful model for investigating neural and social regulation of cardiac function. Cardiac regulation has not been studied previously in the prairie vole. Radiotelemetry transmitters were implanted into adult female prairie voles under anesthesia, and electrocardiographic parameters were recorded. Autonomic blockade was performed using atenolol (8 mg/kg ip) and atropine methyl nitrate (4 mg/kg ip). Several variables were evaluated, including heart rate (HR), HR variability and the amplitude of respiratory sinus arrhythmia. Sympathetic blockade significantly reduced HR. Parasympathetic blockade significantly increased HR, and reduced HR variability and the amplitude of respiratory sinus arrhythmia. Combined autonomic blockade significantly increased HR, and reduced HR variability and respiratory sinus arrhythmia amplitude. The data indicate that autonomic function in prairie voles shares similarities with primates, with a predominant vagal influence on cardiac regulation. The current results provide a foundation for studying neural and social regulation of cardiac function during different behavioral states in this socially monogamous rodent model. PMID:17107695

Comparative analysis of USA300 virulence determinants in a rabbit model of skin and soft tissue infection.

PubMed

Kobayashi, Scott D; Malachowa, Natalia; Whitney, Adeline R; Braughton, Kevin R; Gardner, Donald J; Long, Dan; Bubeck Wardenburg, Juliane; Schneewind, Olaf; Otto, Michael; Deleo, Frank R

2011-09-15

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are frequently associated with strains harboring genes encoding Panton-Valentine leukocidin (PVL). The role of PVL in the success of the epidemic CA-MRSA strain USA300 remains unknown. Here we developed a skin and soft tissue infection model in rabbits to test the hypothesis that PVL contributes to USA300 pathogenesis and compare it with well-established virulence determinants: alpha-hemolysin (Hla), phenol-soluble modulin-alpha peptides (PSMα), and accessory gene regulator (Agr). The data indicate that Hla, PSMα, and Agr contribute to the pathogenesis of USA300 skin infections in rabbits, whereas a role for PVL could not be detected.

[Traumatic intracerebral pneumocephalus communicating with two different paranasal sinuses: a case report].

PubMed

Wakamoto, H; Miyazaki, H; Hayashi, T; Shimamoto, Y; Ishiyama, N

1998-02-01

We report a case of a 17-year-old male who had hit the front of his head in a traffic accident. CT scan revealed contusional hemorrhage and pneumocephalus of the left frontal lobe 10 hours after the accident. A month later he complained of rhinorrhea and CT scan revealed intracerebral pneumocephalus. One day he complained of headache and began to vomit after he sneezed. CT scan revealed that the pneumocephalus had become worse and air had spread throughout the subarachnoid space. Bone CT scan revealed the air communicated from the frontal sinus to the intracerebral air cavity. 3D-CT scan revealed bone defect in the roof of the ethmoid sinus. The intraoperative findings revealed that the intracerebral air cavity communicated with the frontal sinus and ethmoid sinus. Though the brain which dropped into the paranasal sinus, adhered to the dura mater around the bone defect, a part of the brain had come off from the dura mater around the frontal sinus. We suspected that the intracerebral air cavity communicated with the frontal sinus initially. When the air cavity communicated with the ethmoid sinus secondarily, intracranial pressure abated and air came into the subarachnoid space from the frontal sinus.

Rapid transcapillary exchange and unidirectional neuronal uptake of noradrenaline in the perfused rabbit heart.

PubMed Central

Mann, G E; Yudilevich, D L

1984-01-01

Capillary permeability and cellular uptake of noradrenaline by the isolated artificially perfused rabbit heart was measured using rapid (less than 30 s) single-circulation tracer-dilution techniques. In a single coronary circulation capillary extractions of L-[14C]noradrenaline and D-[3H]mannitol (extracellular reference) relative to an intravascular marker, 125I-labelled albumin, were similar and above 60%. The 'apparent' volume of distribution for tracer noradrenaline was 2.5-fold larger than that measured for D-mannitol (0.32 ml g-1) suggesting cellular uptake of the amine. Unidirectional noradrenaline uptake was estimated by directly comparing coronary sinus dilution profiles of L-[3H]noradrenaline and D-[14C]mannitol. Michaelis-Menten saturation kinetics based on a single-entry system were determined (Km = 2.8 +/- 1.5 microM, Vmax = 2.1 +/- 0.5 nmol min-1 g-1, n = 4) by perfusing hearts with varying concentrations of L-noradrenaline (1-10 microM). Various known inhibitors of noradrenaline uptake were investigated to determine whether uptake was mediated by neuronal (uptake1) and/or extraneuronal (uptake2) mechanisms. Desipramine (5 microM), imipramine (5 microM) and metaraminol (2 microM) resulted in a 66-94% inhibition of noradrenaline influx. In comparison, the steroids, 17 beta-oestradiol (1 microM) and corticosterone (10 microM), and the noradrenaline metabolite normetanephrine (5 microM) caused virtually no inhibitory effects. The beta-adrenergic antagonist propranolol (5 microM) was also relatively ineffective. These results together with the kinetic constants estimated suggest that the rapid noradrenaline uptake reflects transport into adrenergic neurones lying in the coronary interstitium. The high resolution of this paired-tracer dilution technique has permitted a 'non-invasive' study of neuronal uptake mechanisms and its application may be of clinical value. PMID:6425496

Regression of aortic valve stenosis by ApoA-I mimetic peptide infusions in rabbits

PubMed Central

Busseuil, D; Shi, Y; Mecteau, M; Brand, G; Kernaleguen, A-E; Thorin, E; Latour, J-G; Rhéaume, E; Tardif, J-C

2008-01-01

Background and purpose: Aortic valve stenosis (AVS) is the most common valvular heart disease, and standard curative therapy remains open heart surgical valve replacement. The aim of our experimental study was to determine if apolipoprotein A-I (ApoA-I) mimetic peptide infusions could induce regression of AVS. Experimental approach: Fifteen New Zealand White male rabbits received a cholesterol-enriched diet and vitamin D2 until significant AVS was detected by echocardiography. The enriched diet was then stopped to mimic cholesterol-lowering therapy and animals were allocated randomly to receive saline (control group, n=8) or an ApoA-I mimetic peptide (treated group, n=7), three times per week for 2 weeks. Serial echocardiograms and post mortem valve histology were performed. Key results: Aortic valve area increased significantly by 25% in the treated group after 14 days of treatment (P=0.012). Likewise, aortic valve thickness decreased by 21% in the treated group, whereas it was unchanged in controls (P=0.0006). Histological analysis revealed that the extent of lesions at the base of valve leaflets and sinuses of Valsalva was smaller in the treated group compared with controls (P=0.032). The treatment also reduced calcification, as revealed by the loss of the positive relationship observed in the control group (r=0.87, P=0.004) between calcification area and aortic valve thickness. Conclusions and implications: Infusions of ApoA-I mimetic peptide lead to regression of experimental AVS. These positive results justify the further testing of high-density lipoprotein (HDL)-based therapies in patients with valvular aortic stenosis. Regression of aortic stenosis, if achieved safely, could transform the clinical treatment of this disease. PMID:18414386

Prevention of Adverse Electrical and Mechanical Remodeling with Bi-Ventricular Pacing in a Rabbit Model of Myocardial Infarction

PubMed Central

Saba, Samir; Mathier, Michael A.; Mehdi, Haider; Gursoy, Erdal; Liu, Tong; Choi, Bum-Rak; Salama, Guy; London, Barry

2008-01-01

Background: Biventricular (BIV) pacing can improve cardiac function in heart failure (HF). Objective: To investigate the mechanisms of benefit of BIV pacing using a rabbit model of myocardial infarction (MI). Methods: New Zealand White rabbits were divided into 4 groups: sham-operated (C), MI with no pacing (MI), MI with right ventricular pacing (MI+RV), and MI with BIV pacing (MI+BIV), and underwent serial electrocardiograms and echocardiograms. At 4 weeks, hearts were excised and tissue was extracted from various areas of the left ventricle (LV). Results: Four weeks after coronary ligation, BIV pacing prevented systolic and diastolic dilation of the LV as well as the reduction in its fractional shortening, restored the QRS width and the rate-dependent QT intervals to their baseline values, and prevented the decline of the ether-a-go-go (erg) protein levels. This prevention of remodeling was not documented in the MI+RV groups. Conclusions: In this rabbit model of BIV pacing and MI, we demonstrate prevention of adverse mechanical and electrical remodeling of the heart. These changes may underlie some of the benefits seen with BIV pacing in HF patients with more severe LV dysfunction. PMID:18180026

Effect of Glyceraldehyde Cross-Linking on a Rabbit Bullous Keratopathy Model.

PubMed

Wang, Mengmeng

2015-01-01

Background. To evaluate the effects of corneal glyceraldehyde CXL on the rabbit bullous keratopathy models established by descemetorhexis. Methods. Fifteen rabbits were randomly divided into five groups. Group A (n = 3) is the control group. The right eyes of animals in Groups B,C, D, and E (n = 3, resp.) were suffered with descemetorhexis procedures. From the 8th day to the 14th day postoperatively, the right eyes in Groups C and D were instilled with hyperosmolar drops and glyceraldehyde drops, respectively; the right eyes in Group E were instilled with both hyperosmolar drops and glyceraldehyde drops. Central corneal thickness (CCT), corneal transparency score, and histopathological analysis were applied on the eyes in each group. Results. Compared with Group A, statistically significant increase in CCT and corneal transparency score was found in Groups B, C, D, and E at 7 d postoperatively (P < 0.05) and in Groups C, D, and E at 14 d postoperatively (P < 0.05). Conclusion. Chemical CXL technique using glyceraldehyde improved the CCT and corneal transparency of the rabbit bullous keratopathy models. Topical instillation with glyceraldehyde and hyperosmolar solutions seems to be a good choice for the bullous keratopathy treatment.

Nitrite therapy prevents chlorine gas toxicity in rabbits

PubMed Central

Honavar, Jaideep; Doran, Stephen; Ricart, Karina; Matalon, Sadis; Patel, Rakesh P.

2017-01-01

Chlorine (Cl2) gas exposure and toxicity remains a concern in military and industrial sectors. While post-Cl2 exposure damage to the lungs and other tissues has been documented and major underlying mechanisms elucidated, no targeted therapeutics that are effective when administered post-exposure, and which are amenable to mass-casualty scenarios have been developed. Our recent studies show nitrite administered by intramuscular (IM) injection post-Cl2 exposure is effective in preventing acute lung injury and improving survival in rodent models. Our goal in this study was to develop a rabbit model of Cl2 toxicity and test whether nitrite affords protection in a non-rodent model. Exposure of New Zealand White rabbits to Cl2 gas (600ppm, 45min) caused significant increases in protein and neutrophil accumulation in the airways and ~35% mortality over 18h. Nitrite administered 30min post Cl2 exposure by a single IM injection, at 1mg/Kg or 10mg/Kg, prevented indices of acute lung injury at 6h by up to 50%. Moreover, all rabbits that received nitrite survived over the study period. These data provide further rationale for developing nitrite as post-exposure therapeutic to mitigate against Cl2 gas exposure injury. PMID:28237808

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.

Is the Maxillary Sinus Really Suitable in Sex Determination? A Three-Dimensional Analysis of Maxillary Sinus Volume and Surface Depending on Sex and Dentition.

PubMed

Möhlhenrich, Stephan Christian; Heussen, Nicole; Peters, Florian; Steiner, Timm; Hölzle, Frank; Modabber, Ali

2015-11-01

The morphometric analysis of maxillary sinus was recently presented as a helpful instrument for sex determination. The aim of the present study was to examine the volume and surface of the fully dentate, partial, and complete edentulous maxillary sinus depending on the sex. Computed tomography data from 276 patients were imported in DICOM format via special virtual planning software, and surfaces (mm) and volumes (mm) of maxillary sinuses were measured. In sex-specific comparisons (women vs men), statistically significant differences for the mean maxillary sinus volume and surface were found between fully dentate (volume, 13,267.77 mm vs 16,623.17 mm, P < 0.0001; surface, 3480.05 mm vs 4100.83 mm, P < 0.0001) and partially edentulous (volume, 10,577.35 mm vs 14,608.10 mm, P = 0.0002; surface, 2980.11 mm vs 3797.42 mm, P < 0.0001) or complete edentulous sinuses (volume, 11,200.99 mm vs 15,382.29 mm, P < 0.0001; surface, 3118.32 mm vs 3877.25 mm, P < 0.0001). For males, the statistically different mean values were calculated between fully dentate and partially edentulous (volume, P = 0.0022; surface, P = 0.0048) maxillary sinuses. Between the sexes, no differences were only measured for female and male partially dentate fully edentulous sinuses (2 teeth missing) and between partially edentulous sinuses in women and men (1 teeth vs 2 teeth missing). With a corresponding software program, it is possible to analyze the maxillary sinus precisely. The dentition influences the volume and surface of the pneumatic maxillary sinus. Therefore, sex determination is possible by analysis of the maxillary sinus event through the increase in pneumatization.

An easy access to retrieve dental implants displaced into the maxillary sinus: the bony window technique.

PubMed

Biglioli, Federico; Chiapasco, Matteo

2014-12-01

To present the authors' experience concerning the removal of dental implants displaced in the maxillary sinus via an intraoral approach consisting of the creation of a bony window pedicled to the maxillary sinus membrane. Thirty-six systemically healthy patients, presenting with oral implants displaced into the maxillary sinus, but with no signs of acute or chronic sinusitis, were consecutively treated between 2002 and 2012 via an intraoral approach with the bony window technique. Removal of oral implants from the maxillary sinus was achieved in all patients, and postoperative recovery was uneventful in all of them. Computed tomographies performed after surgery showed no signs of residual sinus infection in all patients and a complete ossification of the bony window margins. Twelve of the 36 treated patients were treated with a sinus grafting procedure 12-18 months after in the same areas previously treated with the bone lid technique. Seventeen implants were placed in the grafted areas 6-9 months later and, after a further waiting period needed for osseointegration, the treated patients were rehabilitated with implant-supported prostheses. The survival rate of implants was 100%, and no complications related to the sinuses and implants were recorded. Results from this study seem to demonstrate that the bony window technique is a safe and easy way to remove oral implants from the maxillary sinus under local anesthesia. The surgical access is hardly visible 6-12 months after surgery, and maxillary sinuses appeared free from residual pathology in all treated patients. Finally, this procedure allows a second-stage sinus grafting procedure via a lateral approach as in a previously untreated maxillary sinus, thus allowing an implant-supported prosthetic restoration. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The European positional paper on rhinosinusitis and nasal polyps: has the introduction of guidance on the management of sinus disease affected uptake of surgery and acute admissions for sinusitis?

PubMed

Cosway, Ben; Tomkinson, Alun; Owens, David

2013-03-01

Rhinosinusitis is a common condition with adults experiencing 2-5 episodes per year. The European Positional Paper on Rhinosinusitis and Nasal Polyps (EP3OS) published in 2005 and updated in 2007 provided evidence-based guidelines on the management of sinus disease promoting a conservative approach to treatment. This study examines the effect of EP3OS on sinus surgery uptake and acute admissions for sinusitis in England and Wales. A retrospective study using the national electronic health databases of England (Hospital Episodes Statistics, HES online) and Wales (Patient Episodes Database of Wales, PEDW) was undertaken from 2000 to 2010 using the OPCS-4 codes E12-E17 (sinus surgery) and ICD10 code J01 (acute admission for sinusitis). Data were analysed for effect following the introduction of the EP3OS in 2005 using linear regression and Chi squared analysis. 116,370 sinus procedures and 10,916 acute admissions for sinusitis were made during the study period. No significant decrease in sinus surgery procedures occurred following the introduction of the EP3OS as may have been expected (p > 0.05), although subgroup analysis suggested a significant increase in Wales (p < 0.05). In addition, significant increases in acute admissions for sinusitis were observed following the introduction of EP3OS (p < 0.05). However, subgroup analysis suggested this was not the case in Wales (p > 0.05). The EP3OS appears to have had little impact on the rates of sinus surgery but more conservative approaches to managing of sinus disease may have led to an increase in acute admissions. Further research is required to investigate whether changes in practice were adopted.

Surgical treatment of aspirin triad sinusitis.

PubMed

McFadden, E A; Woodson, B T; Fink, J N; Toohill, R J

1997-01-01

Aspirin sensitivity, asthma, and chronic sinusitis with polyposis comprises the syndrome of Aspirin Triad (AT). The sinusitis associated with this disease is often fulminate and difficult to treat. In order to evaluate the surgical treatment of chronic sinusitis of AT a 17-year retrospective study of 80 patients was performed. Friedman Class III or IV sinus CT scans were present in 73 patients (90%) preoperatively. Twenty-five patients (30.1%) had steroid-dependent asthma and an additional 40 (50%) required intermittent oral steroids for asthma control. All patients underwent bilateral sinus surgery by either a conservative or a radical approach. Patients were followed from 3 weeks to 16 years postoperatively, with an average followup of 3 years. Sixty-eight patients (85%) had significant improvement in their sinus symptoms and 67 (83%) had relief of their asthma. The eight patients (10%) who remained steroid dependent required smaller doses of steroids. Seven patients (8.8%) had nonoperative orbital complications. There was a significant incidence of revision surgery after both conservative and radical sinus procedures. We conclude that surgical treatment by either a conservative or a radical approach controlled the sinusitis in the majority of AT patients, but neither was effective in eliminating the need for subsequent sinus surgery in a significant number of patients with severe sinus disease (Classes III and IV). Control of the sinus disease has a definite beneficial effect on steroid dependency and the need for intermittent oral steroids in managing the asthma in AT. We recommend conservative surgery in the surgical treatment of these patients. AT patients also require close long-term followup with intense medical management of their chronic respiratory inflammation that appears to put them at increased risk for nonoperative complications of their severe sinusitis.

Sinus x-ray

MedlinePlus

Paranasal sinus radiography; X-ray - sinuses ... sinus x-ray is taken in a hospital radiology department. Or the x-ray may be taken ... Brown J, Rout J. ENT, neck, and dental radiology. In: Adam A, Dixon AK, Gillard JH, Schaefer- ...

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

PubMed Central

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

2013-01-01

Adjusting hemodynamics via flow diverter (FD) implantation is emerging as a novel method of treating cerebral aneurysms. However, most previous FD-related hemodynamic studies were based on virtual FD deployment, which may produce different hemodynamic outcomes than realistic (in vivo) FD deployment. We compared hemodynamics between virtual FD and realistic FD deployments in rabbit aneurysm models using computational fluid dynamics (CFD) simulations. FDs were implanted for aneurysms in 14 rabbits. Vascular models based on rabbit-specific angiograms were reconstructed for CFD studies. Real FD configurations were reconstructed based on micro-CT scans after sacrifice, while virtual FD configurations were constructed with SolidWorks software. Hemodynamic parameters before and after FD deployment were analyzed. According to the metal coverage (MC) of implanted FDs calculated based on micro-CT reconstruction, 14 rabbits were divided into two groups (A, MC >35%; B, MC <35%). Normalized mean wall shear stress (WSS), relative residence time (RRT), inflow velocity, and inflow volume in Group A were significantly different (P<0.05) from virtual FD deployment, but pressure was not (P>0.05). The normalized mean WSS in Group A after realistic FD implantation was significantly lower than that of Group B. All parameters in Group B exhibited no significant difference between realistic and virtual FDs. This study confirmed MC-correlated differences in hemodynamic parameters between realistic and virtual FD deployment. PMID:23823503

Overview of Frontal Sinus Pathology and Management.

PubMed

Vázquez, Alejandro; Baredes, Soly; Setzen, Michael; Eloy, Jean Anderson

2016-08-01

The frontal sinus is the most complex of all paranasal sinuses. Given its proximity to the cranial vault and orbit, frontal sinus pathology can progress to involve these structures and lead to significant morbidity, or even mortality. Surgical management of the frontal sinus is technically challenging. Various open and endoscopic surgical techniques are available to the otolaryngologist. This article presents an overview of the major disease entities that affect the frontal sinus, with a special emphasis on treatment principles and surgical management. Copyright © 2016 Elsevier Inc. All rights reserved.

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 treating IVCTT in rabbit model.« less

Changes of renal sinus fat and renal parenchymal fat during an 18-month randomized weight loss trial.

PubMed

Zelicha, Hila; Schwarzfuchs, Dan; Shelef, Ilan; Gepner, Yftach; Tsaban, Gal; Tene, Lilac; Yaskolka Meir, Anat; Bilitzky, Avital; Komy, Oded; Cohen, Noa; Bril, Nitzan; Rein, Michal; Serfaty, Dana; Kenigsbuch, Shira; Chassidim, Yoash; Sarusi, Benjamin; Thiery, Joachim; Ceglarek, Uta; Stumvoll, Michael; Blüher, Matthias; Haviv, Yosef S; Stampfer, Meir J; Rudich, Assaf; Shai, Iris

2018-08-01

Data regarding the role of kidney adiposity, its clinical implications, and its dynamics during weight-loss are sparse. We investigated the effect of long-term weight-loss induced intervention diets on dynamics of renal-sinus-fat, an ectopic fat depot, and %renal-parenchymal-fat, lipid accumulation within the renal parenchyma. We randomized 278 participants with abdominal obesity/dyslipidemia to low-fat or Mediterranean/low-carbohydrate diets, with or without exercise. We quantified renal-sinus-fat and %renal-parenchymal-fat by whole body magnetic-resonance-imaging. Participants (age = 48 years; 89% men; body-mass-index = 31 kg/m 2 ) had 86% retention to the trial after 18 months. Both increased renal-sinus-fat and %renal-parenchymal-fat were directly associated with hypertension, and with higher abdominal deep-subcutaneous-adipose-tissue and visceral-adipose-tissue (p of trend < 0.05 for all) after adjustment for body weight. Higher renal-sinus-fat was associated with lower estimated-glomerular-filtration-rate and with higher microalbuminuria and %HbA1C beyond body weight. After 18 months of intervention, overall renal-sinus-fat (-9%; p < 0.05 vs. baseline) but not %renal-parenchymal-fat (-1.7%; p = 0.13 vs. baseline) significantly decreased, and similarly across the intervention groups. Renal-sinus-fat and %renal-parenchymal-fat changes were correlated with weight-loss per-se (p < 0.05). In a model adjusted for age, sex, and visceral-adipose-tissue changes, 18 months reduction in renal-sinus-fat associated with decreased pancreatic, hepatic and cardiac fats (p < 0.05 for all) and with decreased cholesterol/high-density lipoprotein-cholesterol (HDL-c) (β = 0.13; p = 0.05), triglycerides/HDL-c (β = 0.13; p = 0.05), insulin (β = 0.12; p = 0.05) and gamma glutamyl transpeptidase (β = 0.24; p = 0.001), but not with improved renal function parameters or blood pressure. Decreased intake of sodium was associated with a reduction in %renal-parenchymal-fat, after adjustment for 18 months weight-loss (β = 0.15; p = 0.026) and hypertension (β = 0.14; p = 0.04). Renal-sinus-fat and renal-parenchymal-fat are fairly related to weight-loss. Decreased renal-sinus-fat is associated with improved hepatic parameters, independent of changes in weight or hepatic fat, rather than with improved renal function or blood pressure parameters. CLINICALTRIALS. NCT01530724. Copyright © 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

[MODEL ESTABLISHMENT, MRI AND PATHOLOGICAL FEATURES OF EARLY STEROID-INDUCED AVASCULAR NECROSIS OF FEMORAL HEAD IN RABBIT].

PubMed

Zhang, Liyan; Sun, Xin; Tian, Dan; Xu, Rui; Lei, Hao; Al, Jinhui; Zhao, Bo; Chen, Jiying; Chai, Wei; Ma, Shoucheng; Liu, Weijia; Shen, Siyuan

2015-10-01

To establish an rabbit model of early steroid-induced avascular necrosis of the femoral head (SANFH) and evaluate its validity with MRI and pathological examination. Twenty 6-month-old rabbits (weighing, 2-3 kg) were randomly divided into 2 groups (control group and model group), 10 rabbits in each group. Dexamethasone sodium phosphate solution (10 mg/kg) was injected into bilateral gluteus in model group, and the same amount of saline was injected in control group, every 3 days for 14 times. General observation was done after modelling. Osteonecrosis was verified by pathological observation and MRI findings at 6 weeks. After 6 weeks, rabbits did not show obvious changes in control group; increased hair removal, decreased food intake, and slight limp were observed in model group. The MRI results showed normal shape of the bilateral femoral head and no abnormal signals in control group; irregular shape of the bilateral femoral head and a slice of irregular abnormal signals were observed, and necrosis and cystolization of the subchondral bone and sparse changes of trabecular bone were shown in model group. General observation from coronal section of femoral head showed smooth red cartilage surface in control group; on the contrary, the cartilage surface of the femoral head became dull, thin even visible hemorrhage under articular cartilage and necrosis of the femoral head were observed. The histopathological examination indicated that trabecular bone of the femoral head in control group was massive, thick, and close and osteocytes in the bone lacunae had normal shapes. The osseous trabecular became thinner and broken; karyopyknosis of osteocytes and bone empty lacunae could be obviously seen in model. group. The rates of empty lacunae were 8.0% ± 0.5% in control group and 49.0% ± 0.3% in model group, showing significant difference (t = 21.940, P = 0.000). Establishing a model of early SANFH through injecting short-term, shock, and high dose of dexamethasone, and it can been evaluated effectively with MRI and pathological examination.

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

PubMed

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

2010-01-01

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

Interspecies comparison of subchondral bone properties important for cartilage repair.

PubMed

Chevrier, Anik; Kouao, Ahou S M; Picard, Genevieve; Hurtig, Mark B; Buschmann, Michael D

2015-01-01

Microfracture repair tissue in young adult humans and in rabbit trochlea is frequently of higher quality than in corresponding ovine or horse models or in the rabbit medial femoral condyle (MFC). This may be related to differences in subchondral properties since repair is initiated from the bone. We tested the hypothesis that subchondral bone from rabbit trochlea and the human MFC are structurally similar. Trochlea and MFC samples from rabbit, sheep, and horse were micro-CT scanned and histoprocessed. Samples were also collected from normal and lesional areas of human MFC. The subchondral bone of the rabbit trochlea was the most similar to human MFC, where both had a relatively thin bone plate and a more porous and less dense character of subchondral bone. MFC from animals all displayed thicker bone plates, denser and less porous bone and thicker trabeculae, which may be more representative of older or osteoarthritic patients, while both sheep trochlear ridges and the horse lateral trochlea shared some structural features with human MFC. Since several cartilage repair procedures rely on subchondral bone for repair, subchondral properties should be accounted for when choosing animal models to study and test procedures that are intended for human cartilage repair. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Passive vs. active safety belt systems in Volkswagen rabbits : a comparison of owner use habits and attitudes

DOT National Transportation Integrated Search

1976-08-01

The overall objective of this research is to measure usage of, and attitudes toward, the passive restraint system, compared with the active restraint system on 1975 model year Volkswagen Rabbits. Methods used to carry out the research include: Interv...

Treatment of the superior sagittal sinus and transverse sinus thrombosis associated with intracranial hemorrhage with the mechanical thrombectomy and thrombolytics: Case report.

PubMed

Liu, Yuchun; Li, Keqin; Huang, Yi; Sun, Jie; Gao, Xiang

2017-12-01

The superior sagittal sinus (SSS) and transverse sinus are the major dural sinuses that receive a considerable amount of venous drainage. The occlusion of them has been suggested to cause intracranial hypertension, hemorrhage, and lead to potentially fatal consequences. We reported a 35-year-old woman with headache presented to our emergency department with a decreased level of consciousness and epileptic seizures. The examination of speech, higher mental function, and cranial nerve were normal. Computed tomography (CT) demonstrated both subarachnoid and intraparenchymal hemorrhage and brain edema at the right temporal lobe accompanied by high density shadow in the right transverse sinus. Digital subtraction angiography (DSA) revealed extensive thrombosis of the SSS and bilateral transverse sinus. The SSS and transverse sinus thrombosis, accompanied by right temporal lobe hemorrhage, subarachnoid hemorrhage (SAH). An emergent mechanical thrombectomy by placed Solitair AB stent in the SSS, respectively, passed left and right sigmoid sinus-transverse sinus route. We removed the most clots, DSA revealed recanalization of the SSS and left transverse sinus was seen with normalization of the venous outflow, the occlusion of right transverse sinus was still present. There were 4 hours after patient back to neurosurgical intensive care unit (NICU), patient appeared anisocoria (R/L:4.0/2.5 mm), bilateral light reflexes disappeared, then we took a CT reexamination revealed intraparenchymal hemorrhage increased, brain edema was aggravated at the left temporal lobe, and mild midline shift. Subsequently, we performed decompressive hemicraniectomy and puncture the hematoma supplemented by B ultrasonic. Anticoagulation treatment was initiated 24 hours after surgery, and follow-up DSA showed gradually improved patency in the SSS and bilateral transverse sinus. Despite occlusion of the SSS and bilateral transverse sinus, patient's symptoms resolved after the operations and he was discharged without complications. The favorable clinical outcome after complete occlusion of the SSS and transverse sinus, accompanied by right temporal lobe hemorrhage, SAH has rarely been reported and it might be explained by our timely surgical intervention and development of compensatory cerebral collateral circulation.

Dural venous sinuses distortion and compression with supratentorial mass lesions: a mechanism for refractory intracranial hypertension?

PubMed Central

Qureshi, Adnan I.; Qureshi, Mushtaq H.; Majidi, Shahram; Gilani, Waqas I.; Siddiq, Farhan

2014-01-01

Objective To determine the effect of supratentorial intraparenchymal mass lesions of various volumes on dural venous sinuses structure and transluminal pressures. Methods Three set of preparations were made using adult isolated head derived from fresh human cadaver. A supratentorial intraparenchymal balloon was introduced and inflated at various volumes and effect on dural venous sinuses was assessed by serial intravascular ultrasound, computed tomographic (CT), and magnetic resonance (MR) venograms. Contrast was injected through a catheter placed in sigmoid sinus for both CT and MR venograms. Serial trasluminal pressures were measured from middle part of superior sagittal sinus in another set of experiments. Results At intraparenchymal balloon inflation of 90 cm3, there was attenuation of contrast enhancement of superior sagittal sinus with compression visualized in posterior part of the sinus without any evidence of compression in the remaining sinus. At intraparenchymal balloon inflation of 180 and 210 cm3, there was compression and obliteration of superior sagittal sinus throughout the length of the sinus. In the coronal sections, at intraparenchymal balloon inflations of 90 and 120 cm3, compression and obliteration of the posterior part of superior sagittal sinus were visualized. In the axial images, basal veins were not visualized with intraparenchymal balloon inflation of 90 cm3 or greater although straight sinus was visualized at all levels of inflation. Trasluminal pressure in the middle part of superior sagittal sinus demonstrated a mild increase from 0 cm H2O to 0.4 cm H2O and 0.5 cm H2O with inflation of balloon to volume of 150 and 180 cm3, respectively. There was a rapid increase in transluminal pressure from 6.8 cm H2O to 25.6 cm H2O as the supratentorial mass lesion increased from 180 to 200 cm3. Conclusions Our experiments identified distortion and segmental and global obliteration of dural venous sinuses secondary to supratentorial mass lesion and increase in transluminal pressure with large volume lesions. The secondary involvement of dural venous sinuses may represent a mechanism for refractory intracranial hypertension. PMID:24920987

[Radiologic picture of maxillary sinus aspergilloma].

PubMed

Kaczmarek, I; Bilska, J; Osmola, K; Nowaczyk, M T

2010-06-01

Mycotic infection of paranasal sinus could be the etiological factor of chronic sinusitis. The increase in number of fungal sinusitis cases have been reported recently among nonimmunocompromised patient after endodontic treatment of maxillary teeth. Nonspecific clinical signs and incorrect radiologic pictures interpretation as well as loss of therapeutic standards seems to be the cause of false negative diagnosis and difficulties in treatment of fungal sinusitis. Clinical and radiological picture of maxillary sinus aspergillosis was described in this paper. In the period of 2006-2009 in the Department of Maxillo-Facial Surgery 19 patient with fungal maxillary sinusitis was treated. The endodontic treatment of maxillary teeth of the related side was performed previously in 80% examined cases. In 2 cases there were immunocompromised patients with immunosuppressive treatment. In 16 cases patients were referred to our Department due to metallic foreign body of the maxillary sinus. Routine diagnostic radiological imaging was performed in each case: paranasal sinus view--Water's view and panoramic radiograph (orthopantomograph). In 4 cases imaging was extended with computer tomography (CT) visualization. The surgical treatment was performed in each case. The final diagnosis was puted on histopathological examination and fungal culture. In 16 cases of analysed group histopathological examination and fungal culture revealed aspergilosis. In 2 cases fungal culture was negative, but histopathology slices confirm presence of hyphae of Aspergillus. In 1 case the root canal sealer was found in the maxillary sinus. In none case invasive form of aspergillosis was confirmed. In all cases Water's view of paranasal sinuses and ortopantomograph showed partially or totally clouded sinus with well-defined, single or multifocal radiopaque object similar to metallic foreign body. Characteristic finding in CT imaging was well-defined radiodence concretions that have been attributed to calcium deposits in inflammatory changed mucosa, that might suggest "foreign body" picture. In 1 to 3 years follow-up control there was a recurrence of symptoms in one case. Foreign body of maxillary sinus have to be differentiated with aspergilosis. Metallic "foreign body" view in maxillary sinus seems to be characteristic sign of aspergillosis. The most often form of maxillary sinus aspergilosis is aspergilloma.

Protection by scoparone against the alterations of plasma lipoproteins, vascular morphology and vascular reactivity in hyperlipidaemic diabetic rabbit.

PubMed

Huang, H C; Weng, Y I; Lee, C R; Jan, T R; Chen, Y L; Lee, Y T

1993-12-01

1. The in vivo pharmacological effects of scoparone (6,7-dimethoxycoumarin) in a hyperlipidaemic diabetic rabbit model were investigated. 2. Three groups of rabbits were studied: (1) normal, (2) hyperlipidaemic and diabetic-untreated and (3) hyperlipidaemic and diabetic-scoparone treated. The hyperlipidaemic diabetic rabbits were fed with 1% cholesterol and treated with alloxan, a diabetogenic agent. The plasma levels of total cholesterol, total triglyceride, very low-density lipoprotein (VLDL) cholesterol, low density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol were markedly increased as soon as the rabbit became diabetic at the second week. Scoparone-treatment (5 mg kg-1 day-1, s.c.) significantly reduced the plasma lipid and lipoprotein cholesterol levels of the hyperlipidaemic diabetic rabbit to 73.3% of total cholesterol, 48.3% of total triglyceride, 66.0% of VLDL cholesterol, 55.7% of LDL cholesterol and 79.5% of HDL cholesterol. 3. Six weeks after cholesterol-feeding, the aortic arch and thoracic aorta were dissected for morphological and functional studies. In vascular rings from the untreated hyperlipidaemic diabetic rabbit, there was intimal thickening with accumulation of fatty streaks, foam cells and migration of smooth muscle cells to the intima. In the rabbits treated with scoparone, there were fewer pathological morphology changes found in vascular segments than in the untreated hyperlipidaemic diabetic rabbits. 4. In the vascular reactivity experiments, the phenylephrine-induced contraction and nitroprusside induced dilatation did not differ significantly among the three rabbit groups, except that the contraction was enhanced in the thoracic aorta of hyperlipidaemic diabetic rabbits either untreated or treated withscoparone, as compared to the normal group, and the sensitivity to nitroprusside was increased in the thoracic aorta of the scoparone-treated group as compared to the untreated group.5. The endothelium-dependent dilatation induced by acetylcholine was significantly attenuated in both the aortic arch and thoracic aorta from the hyperlipidaemic diabetic rabbits as compared to the normal rabbits. This attenuation was partially prevented, when scoparone (5 mg kg-1) was administered daily.6. These results suggest that scoparone protects against some alterations of plasma lipoproteins,vascular morphology and vascular reactivity in the hyperlipidaemic diabetic rabbit. These protective effects of scoparone may be partly related to its free radical scavenging property.

The morphological interaction between the nasal cavity and maxillary sinuses in living humans.

PubMed

Holton, Nathan; Yokley, Todd; Butaric, Lauren

2013-03-01

To understand how variation in nasal architecture accommodates the need for effective conditioning of respired air, it is necessary to assess the morphological interaction between the nasal cavity and other aspects of the nasofacial skeleton. Previous studies indicate that the maxillary sinuses may play a key role in accommodating climatically induced nasal variation such that a decrease in nasal cavity volume is associated with a concomitant increase in maxillary sinus volume. However, due to conflicting results in previous studies, the precise interaction of the nasal cavity and maxillary sinuses, in humans, is unclear. This is likely due to the prior emphasis on nasal cavity size, whereas arguably, nasal cavity shape is more important with regard to the interaction with the maxillary sinuses. Using computed tomography scans of living human subjects (N=40), the goal of this study is to assess the interaction between nasal cavity form and maxillary sinus volume in European- and African-derived individuals with differences in nasal cavity morphology. First, we assessed whether there is an inverse relationship between nasal cavity and maxillary sinus volumes. Next, we examined the relationship between maxillary sinus volume and nasal cavity shape using multivariate regression. Our results show that there is a positive relationship between nasal cavity and maxillary sinus volume, indicating that the maxillary sinuses do not accommodate variation in nasal cavity size. However, maxillary sinus volume is significantly correlated with variation in relative internal nasal breadth. Thus, the maxillary sinuses appear to be important for accommodating nasal cavity shape rather than size. Copyright © 2013 Wiley Periodicals, Inc.

Maxillary Sinus Augmentation for Dental Implant Rehabilitation of the Edentulous Ridge: A Comprehensive Overview of Systematic Reviews.

PubMed

Ting, Miriam; Rice, Jeremy G; Braid, Stanton M; Lee, Cameron Y S; Suzuki, Jon B

2017-06-01

The objective of this systemic review was to perform a comprehensive overview of systematic reviews and meta-analyses of the maxillary sinus augmentation procedure for implant rehabilitation in humans. The following were evaluated in this overview: (1) anatomic variables affecting sinus augmentation, (2) histomorphometric analysis of the grafted sinus, (3) volumetric changes after sinus grafting, and (4) implant survival beyond 1 year. Electronic databases were searched for systematic reviews and meta-analyses of implant-related sinus augmentation published from 1976 to September 2015. The studies selected must identify itself as a systemic review or meta-analysis in the title or abstract and must pertain to sinus augmentation. Thirty-three publications fulfilled the review criteria. The AMSTAR ratings for the 33 chosen reviews scored greater than 3 of 11, with 8 reviews scoring greater or equal to 8 of 11. The outcome of this overview suggested that the following will increase the success of sinus augmentation and survival of implants placed in the grafted sinus: (1) the use of barrier membranes over the lateral window when using a lateral approach to graft the sinus, (2) the use of particulate autogenous bone with or without other substitute graft materials, (3) sinus augmentation without the use of grafting materials may be considered provided that the space between the sinus membrane and floor can be maintained, (4) the use of rough-surfaced implants, (5) simultaneous implant placement with residual bone height greater than 4 mm, and (6) the cessation of smoking.

Frontal sinus revision rate after nasal polyposis surgery including frontal recess clearance and middle turbinectomy: A long-term analysis.

PubMed

Benkhatar, Hakim; Khettab, Idir; Sultanik, Philippe; Laccourreye, Ollivier; Bonfils, Pierre

2018-08-01

To determine the frontal sinus revision rate after nasal polyposis (NP) surgery including frontal recess clearance (FRC) and middle turbinectomy (MT), to search for predictive factors and to analyse surgical management. Longitudinal analysis of 153 patients who consecutively underwent bilateral sphenoethmoidectomy with FRC and MT for NP with a minimum follow-up of 7 years. Decision of revision surgery was made in case of medically refractory chronic frontal sinusitis or frontal mucocele. Univariate and multivariate analysis incorporating clinical and radiological variables were performed. The frontal sinus revision rate was 6.5% (10/153). The mean time between the initial procedure and revision surgery was 3 years, 10 months. Osteitis around the frontal sinus outflow tract (FSOT) was associated with a higher risk of frontal sinus revision surgery (p=0.01). Asthma and aspirin intolerance did not increase the risk, as well as frontal sinus ostium diameter or residual frontoethmoid cells. Among revised patients, 60% required multiple procedures and 70% required frontal sinus ostium enlargement. Our long-term study reports that NP surgery including FRC and MT is associated with a low frontal sinus revision rate (6.5%). Patients developing osteitis around the FSOT have a higher risk of frontal sinus revision surgery. As mucosal damage can lead to osteitis, FSOT mucosa should be preserved during initial NP surgery. However, as multiple procedures are common among NP patients requiring frontal sinus revision, frontal sinus ostium enlargement should be considered during first revision in the hope of reducing the need of further revisions. Copyright © 2018 Elsevier B.V. All rights reserved.

Distribution and mixing of a liquid bolus in pleural space.

PubMed

Bodega, Francesca; Tresoldi, Claudio; Porta, Cristina; Zocchi, Luciano; Agostoni, Emilio

2006-02-28

Distribution and mixing time of boluses with labeled albumin in pleural space of anesthetized, supine rabbits were determined by sampling pleural liquid at different times in various intercostal spaces (ics), and in cranial and caudal mediastinum. During sampling, lung and chest wall were kept apposed by lung inflation. This was not necessary in costo-phrenic sinus. Here, 10 min after injection, lung inflation increased concentration of labeled albumin by 50%. Lung inflation probably displaces some pleural liquid cranio-caudally, increasing labeled albumin concentration caudally to injection point (6th ics), and decreasing it cranially. Boluses of 0.1-1 ml did not preferentially reach mediastinal regions, as maintained by others. Time for an approximate mixing was approximately 1 h for 0.1 ml, and approximately 30 min for 1 ml. This relatively long mixing time does not substantially affect determination of contribution of lymphatic drainage through stomata to overall removal of labeled albumin from 0.3 ml hydrothoraces lasting 3 h [Bodega, F., Agostoni, E., 2004. Contribution of lymphatic drainage through stomata to albumin removal from pleural space. Respir. Physiol. Neurobiol. 142, 251-263].

Maxillary Sinus Dimensions Decrease as Age and Tooth Loss Increase.

PubMed

Velasco-Torres, Miguel; Padial-Molina, Miguel; Avila-Ortiz, Gustavo; García-Delgado, Raúl; OʼValle, Francisco; Catena, Andrés; Galindo-Moreno, Pablo

2017-04-01

To investigate the correlation between patient-dependent variables and dimensional variations of the maxillary sinus. In this cross-sectional study, a total of 394 individual cone-beam computed tomography scans were evaluated by one calibrated examiner to measure the total volume of the maxillary sinus, the distance between the medial and the lateral walls at 5, 10, and 15 mm vertically from the sinus floor, the height of septa (if present), and the height of the maxillary sinus cavity from both the alveolar crest and the sinus floor to the meatus. Recorded patient-dependent variables were age, gender, and edentulism status. Total maxillary sinus volume was significantly smaller in completely and partially edentulous patients than in dentate subjects. This finding was influenced by age, as older patients exhibited less volume, regardless of gender and edentulism status. Age showed an indirect correlation with the distance to the meatus, the sinus volume, and the mediolateral dimensions. Additionally, the prevalence of accessory meatus in this population was 29.19%. The dimensions of the maxillary sinus are influenced by age and edentulism status being reduced by aging and tooth loss.

Quantitative impact of pediatric sinus surgery on facial growth.

PubMed

Senior, B; Wirtschafter, A; Mai, C; Becker, C; Belenky, W

2000-11-01

To quantitatively evaluate the long-term impact of sinus surgery on paranasal sinus development in the pediatric patient. Longitudinal review of eight pediatric patients treated with unilateral sinus surgery for periorbital or orbital cellulitis with an average follow-up of 6.9 years. Control subjects consisted of two groups, 9 normal adult patients with no computed tomographic evidence of sinusitis and 10 adult patients with scans consistent with sinusitis and a history of sinus-related symptoms extending to childhood. Application of computed tomography (CT) volumetrics, a technique allowing for precise calculation of volumes using thinly cut CT images, to the study and control groups. Paired Student t test analyses of side-to-side volume comparisons in the normal patients, patients with sinusitis, and patients who had surgery revealed no statistically significant differences. Comparisons between the orbital volumes of patients who did and did not have surgery revealed a statistically significant increase in orbital volume in patients who had surgery. Only minimal changes in facial volume measurements have been found, confirming clinical impressions that sinus surgery in children is safe and without significant cosmetic sequelae.

Schneider Membrane Elevation in Presence of Sinus Septa: Anatomic Features and Surgical Management

PubMed Central

Beretta, Mario; Cicciù, Marco; Bramanti, Ennio; Maiorana, Carlo

2012-01-01

Maxillary sinus floor elevation via a lateral approach is a predictable technique to increase bone volume of the edentulous posterior maxilla and consequently for dental implants placement. The sinus floor is elevated and it can be augmented with either autologous or xenogeneic bone grafts following an opening bone window created on the facial buccal wall. Maxillary septa are walls of cortical bone within the maxillary sinus. The septa shape has been described as an inverted gothic arch arising from the inferior or lateral walls of the sinus and may even divide the sinus into two or more cavities. Some authors have reported a higher prevalence of septa in atrophic edentulous areas than in nonatrophic ones. Radiographic identification of these structures is important in order to perform the right design of the lateral window during sinus lift. Aim of this investigation is to highlight the correct steps for doing sinus lift surgery in presence of those anatomic variations. Clinicians should always perform clinical and radiographic diagnosis in order to avoid complications related to the sinus lift surgery. PMID:22848223

A Rabbit Model for Assessment of Volatile Metabolite Changes Observed from Skin: a Pressure Ulcer Case Study

PubMed Central

Schivo, Michael; Aksenov, Alexander A; Pasamontes, Alberto; Cumeras, Raquel; Weisker, Sandra; Oberbauer, Anita M; Davis, Cristina E

2017-01-01

Human skin presents a large, easily accessible matrix that is potentially useful for diagnostic applications based on whole body metabolite changes – some of which will be volatile and detected using minimally invasive tools. Unfortunately, identifying skin biomarkers that can be reliably linked to a particular condition is challenging due to a large variability of genetics, dietary intake, environmental exposures within human populations. This leads to a paucity of clinically validated volatile skin biomarker compounds. Animal models present a very convenient and attractive way to circumvent many of the variability issues. The rabbit (Leporidae) is a potentially logistically useful model to study the skin metabolome, but very limited knowledge of its skin metabolites exists. Here we present the first comprehensive assessment of the volatile fraction of rabbit skin metabolites using polydimethylsiloxane sorbent patch sampling in conjunction with gas chromatography / mass spectrometry (GC/MS). A collection of compounds that are secreted from rabbit skin was documented, and predominantly acyclic long-chain alkyls and alcohols were detected. We then utilized this animal model to study differences between intact skin and skin with early pressure ulcers, as the latter are a major problem in intensive care units. Four New Zealand female white rabbits underwent ulcer formation on one ear with the other ear as a control. Early-stage ulcers were created with neodymium magnets. Histologic analysis showed acute heterophilic dermatitis, edema, and micro-hemorrhage on the ulcerated ears with normal findings on the control ears. The metabolomic analysis revealed subtle but noticeable differences, with several compounds associated with the oxidative stress-related degradation of lipids found to be present in greater abundances in ulcerated ears. The metabolomic findings correlate with histologic evidence of early-stage ulcers. We postulate that the Leporidae model recapitulated the vascular changes associated with ulcer formation. This study illustrates the potential usefulness of the Leporidae model for skin metabolome studies as illustrated by this study of early-stage ulcer formation. PMID:28068292

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

PubMed

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

2014-01-01

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

Sinusitis (For Teens)

MedlinePlus

... usually not severe and is easy to treat. What Is Sinusitis? Sinusitis is the medical term for inflammation ( ... try to reduce close contact with anyone who is sneezing often or has signs and symptoms of sinusitis. What Can I Do to Feel Better? If your ...

Effect of Survivin gene therapy via lentivirus vector on the course of intervertebral disc degeneration in an in vivo rabbit model.

PubMed

Yue, Bin; Lin, Yazhou; Ma, Xuexiao; Zhang, Guoqing; Chen, Bohua

2016-11-01

The aim of the current study was to use gene therapy to attenuate or reverse the degenerative process within the intervertabral disc. The effect of survivin gene therapy via lentiviral vector transfection on the course of intervertebral disc degeneration was investigated in the current study in an in vivo rabbit model. A total of 15 skeletally mature female New Zealand White rabbits were randomly divided into three groups: Punctured blank control group (group A, n=5), punctured empty vector control group (group B, n=5) and the treatment group (group C, n=5). Computed tomography‑guided puncture was performed at the L3‑L4 and L4‑L5 discs, in accordance with a previously validated rabbit annulotomy model for intervertebral disc degeneration. After 3 weeks, a lentiviral vector (LV) carrying survivin was injected into the nucleus pulposus. The results demonstrated that through magnetic resonance imaging, histology, gene expression, protein content and apoptosis analyses, group A and B were observed to exhibit disc degeneration, which increased over time, and no significant difference was observed between the two groups (P>0.05). However, there was reduced disc degeneration in group C compared with the punctured control groups, and the difference was statistically significant (P<0.05). Overall, the results of the present study demonstrated that injection of the LV carrying survivin into punctured rabbit intervertebral discs acted to delay changes associated with the degeneration of the discs. Although data from animal models should be extrapolated to the human condition with caution, the present study suggests potential for the use of gene therapy to decelerate disc degeneration.

Esophageal Epithelial Resistance and Lower Esophageal Sphincter Muscle Contraction Increase in a Chronic Diabetic Rabbit Model.

PubMed

Capanoglu, Doga; Coskunsever, Deniz; Olukman, Murat; Ülker, Sibel; Bor, Serhat

2016-07-01

Esophageal motility disorders and possibly gastroesophageal reflux disease are common in patients with diabetes mellitus. We aimed to investigate both the electrophysiological characteristics of the esophageal epithelium and the contractility of the lower esophageal sphincter (LES) muscle in alloxane-induced diabetic rabbits. Electrophysiological properties were measured using an Ussing chamber method. An acid-pepsin model was employed with pH 1.7 or weakly acidic (pH 4) Ringer and/or pepsin. Smooth muscle strips of the LES were mounted in an isolated organ bath. Contractile responses to an electrical field stimulation and cumulative concentrations of acetylcholine were recorded. Contractility of the muscle strips were tested in the presence of Rho-kinase inhibitor (Y-27632) and nonspecific nitric oxide inhibitor (L-NAME). The resistance of diabetic tissue perfused in the pH 1.7 Ringer decreased 17 %; pepsin addition decreased it by 49 %. The same concentrations caused a more distinct loss of resistance in the control tissues (22 and 76 %, p < 0.05). The perfusion of tissues in increased concentrations of luminal and serosal glucose did not change the tissue resistance and voltage. Diabetes significantly increased both the electrical field stimulation and acetylcholine-induced contractions in the LES muscle strips (p < 0.01). Incubation with Y-27632 significantly decreased the acetylcholine-induced contractions in a concentration-dependent manner (p < 0.01). The acid-pepsin model in the diabetic rabbit esophageal tissue had less injury compared with the control. The diabetic rabbit LES muscle had higher contractility, possibly because of the activation of the Rho-Rhokinase pathway. Our results show that in a chronic diabetic rabbit model the esophagus resists reflux by activating mechanisms of mucosal defense and increasing the contractility of the LES.

Modeling Rabbit Responses to Single and Multiple Aerosol ...

EPA Pesticide Factsheets

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

Evaluation of the Effect of Hemoglobin or Hematocrit Level on Dural Sinus Density Using Unenhanced Computed Tomography

PubMed Central

Cha, Sang-Hoon; Lee, Sung-Hyun; Shin, Dong-Ick

2013-01-01

Purpose To identify the relationship between hemoglobin (Hgb) or hematocrit (Hct) level and dural sinus density using unenhanced computed tomography (UECT). Materials and Methods Patients who were performed UECT and had records of a complete blood count within 24 hours from UECT were included (n=122). We measured the Hounsfield unit (HU) of the dural sinus at the right sigmoid sinus, left sigmoid sinus and 2 points of the superior sagittal sinus. Quantitative measurement of dural sinus density using the circle regions of interest (ROI) method was calculated as average ROI values at 3 or 4 points. Simple regression analysis was used to evaluate the correlation between mean HU and Hgb or mean HU and Hct. Results The mean densities of the dural sinuses ranged from 24.67 to 53.67 HU (mean, 43.28 HU). There was a strong correlation between mean density and Hgb level (r=0.832) and between mean density and Hct level (r=0.840). Conclusion Dural sinus density on UECT is closely related to Hgb and Hct levels. Therefore, the Hgb or Hct levels can be used to determine whether the dural sinus density is within the normal range or pathological conditions such as venous thrombosis. PMID:23225795

Reconstructed bone chip detachment is a risk factor for sinusitis after transsphenoidal surgery.

PubMed

Hsu, Yao-Wen; Ho, Ching-Yin; Yen, Yu-Shu

2014-01-01

Sphenoid sinusitis is a complication associated with endoscopic transsphenoidal pituitary surgery. Studies that address the relationship between methods of sellar defect reconstruction and postoperative sinusitis are rare. The purpose of this study was to investigate the incidence, the possible risk factors, and the causative pathogens of sphenoid sinusitis after endoscopic transsphenoidal pituitary surgery. Prospective cohort study. We performed a prospective analysis of 182 patients with benign pituitary tumor who underwent endoscopic transsphenoidal pituitary surgery and sellar defect reconstruction with bone chip, from July 2008 through July 2011. All patients were followed up with nasal endoscopy for at least 6 weeks. Fifty-seven (31.3%) patients developed postoperative sphenoid sinusitis. Comparing the sinusitis and nonsinusitis groups, we found that bone chip detachment was a significant risk factor for postoperative sinusitis, with a relative risk of 2.86 (64.1% vs. 22.4%). The most common pathogens present in cases of postoperative sinusitis were methicillin-sensitive Staphylococcus aureus, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus. Regular follow-up with nasal endoscopy can prevent delayed diagnosis of postoperative sphenoid sinusitis. Culture-directed antibiotics with aggressive endoscopic debridement are an effective treatment for these patients. An optimal reconstruction strategy should be further developed to reduce bone chip detachment and secondary sinusitis. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

Lack of desensitization of the cough reflex in ovalbumin-sensitized rabbits during exercise.

PubMed

Tiotiu, Angelica; Chenuel, Bruno; Foucaud, Laurent; Demoulin, Bruno; Demoulin-Alexikova, Silvia; Christov, Christo; Poussel, Mathias

2017-01-01

Cough is a major symptom of asthma frequently experienced during exercise but little is known about interactions between cough and exercise. The goal of our study was to clarify the potential modulation of the cough reflex (CR) by exercise in a spontaneously breathing anaesthetized animal model of airway eosinophilic inflammation. Ten ovalbumin (OVA) sensitized adult rabbits and 8 controls were studied. The ventilatory response to direct tracheal stimulation, performed both at rest and during exercise was determined to quantify the incidence and the sensitivity of the CR. Broncho-alveolar lavages (BAL) and cell counts were performed to assess the level of the airway inflammation following OVA-induced sensitization. Exercise was mimicked by Electrically induced hindlimb Muscular Contractions (EMC). Among 494 tracheal stimulations, 261 were performed at rest and 233 at exercise. OVA challenges in sensitized rabbits caused a significant increase in the percentage of eosinophils (p = 0.008) in BAL. EMC increased minute ventilation by 36% and 35% in OVA and control rabbits respectively, compared to rest values. The sensitivity of the CR decreased during exercise compared to baseline in control rabbits (p = 0.0313) while it remained unchanged in OVA rabbits. The desensitization of the CR during exercise in control rabbits was abolished in OVA rabbits. The precise role of airway inflammation in this lack of CR desensitization needs to be further investigated but it might contribute to the exercise-induced cough in asthmatics.

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

EPA Pesticide Factsheets

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

[Effects of simulated weightlessness on pressure-volume relationships of femoral vein of New Zealand Rabbits].

PubMed

Yue, Yong; Yao, Yong-jie; Xie, Xiao-ping; Wang, Bing; Zhu, Qing-sheng; Wu, Xing-yu

2002-12-01

Objective. To observe the changes of pressure-volume relationships of rabbit femoral veins and their structural changes caused by simulated weightlessness. Method. Head-Down Tilt (HDT) -20 degrees rabbit model was used to simulate weightlessness. Twenty four healthy male New Zealand Rabbits were randomly divided into 21 d HDT group,10 d HDT group and control group, (8 in each group). Pressure-volume (P-V) relationship of rabbits femoral veins was measured and the microstructure of the veins was observed. Result. The femoral vein P-V relationship curves of HDT groups showed a larger volume change ratio than that of control group. This change was that 21 d HDT group was even more obvious than that of HDT-10 d group. B1 and B2 in quadratic equations of 21 d HDT group were significantly higher than the values of both 10 d HDT group and control group during expansion (inflow) and collapse (outflow) (P<0.01). The result of histological examination showed that the contents and structure of femoral vein wall of HDT-rabbits changed significantly. Endothelial cells of femoral vein became short and columnar or cubic, some of which fell off. Smooth muscle layer became thinner. Conclusion. Femoral venous compliance increased after weightlessness-simulation and the femoral venous compliance in 21 d-HDT rabbits increased more obviously than that in 10 d-HDT rabbits. The structure of femoral vein wall had changed obviously.

Pharmacokinetic analysis of modified-release metoprolol formulations: An interspecies comparison.

PubMed

De Thaye, Elien; Vervaeck, Anouk; Marostica, Eleonora; Remon, Jean Paul; Van Bocxlaer, Jan; Vervaet, Chris; Vermeulen, An

2017-01-15

In the current study, we investigated the metoprolol absorption kinetics of an in-house produced oral sustained-release formulation, matrices manufactured via prilling, and two commercially available formulations, ZOK-ZID ® (reservoir) and Slow-Lopresor ® (matrix) in both New Zealand White rabbits and Beagle dogs, using a population pharmacokinetic analysis approach. The aim of this study was to compare the in vivo pharmacokinetic (PK) profiles of different formulations based on metoprolol, a selective adrenergic β 1 -receptor antagonist, in dogs and rabbits and to contrast the observed differences. To that end, metoprolol (50 to 200mg) was administered to 6 Beagle dogs and 6 New Zealand White rabbits as a single intravenous (IV) bolus injection and to 8 dogs and 6 rabbits as an oral modified release formulation. To derive pharmacokinetic parameters from the data, a non-linear mixed-effects model was developed using NONMEM ® where the contribution of observations below the limit of detection (BDL, below detection limit) to the parameter estimates was taken into account in the parameter estimation procedure. In both species and for the three modified release formulations, different absorption models were tested to describe the PK of metoprolol following oral dosing. In Beagle dogs, plasma concentration-time profiles were best described using a sequential zero- and first-order absorption model. In rabbits though, the absorption phase was best described using a first-order process only. In both species, the reservoir formulation ZOK-ZID ® was behaving quite similarly. In contrast, the absorption properties of both matrix formulations were rather different between species. This study indicates that the PK of the reservoir formulation is similar in both species, even after accounting for the almost completely missed absorption phase in rabbits. The insights gained further illustrate that rabbits are not very well suited to study the PK of the current matrix formulations in view of their less optimal prolonged release characteristics and the resulting fast decline in metoprolol plasma levels. Copyright © 2016 Elsevier B.V. All rights reserved.

Assessment of ABCG2-mediated transport of pesticides across the rabbit placenta barrier using a novel MDCKII in vitro model

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

Halwachs, Sandra

In humans, the ATP-binding cassette efflux transporter ABCG2 contributes to the fetoprotective barrier function of the placenta, potentially limiting the toxicity of transporter substrates to the fetus. During testing of chemicals including pesticides, developmental toxicity studies are performed in rabbit. Despite its toxicological relevance, ABCG2-mediated transport of pesticides in rabbit placenta has not been yet elucidated. We therefore generated polarized MDCK II cells expressing the ABCG2 transporter from rabbit placenta (rbABCG2) and evaluated interaction of the efflux transporter with selected insecticides, fungicides, and herbicides. The Hoechst H33342 accumulation assay indicated that 13 widely used pesticidal active substances including azoxystrobin, carbendazim,more » chlorpyrifos, chlormequat, diflufenican, dimethoate, dimethomorph, dithianon, ioxynil, methiocarb, propamocarb, rimsulfuron and toclofos-methyl may be rbABCG2 inhibitors and/or substrates. No such evidence was obtained for chlorpyrifos-methyl, epoxiconazole, glyphosate, imazalil and thiacloprid. Moreover, chlorpyrifos (CPF), dimethomorph, tolclofos-methyl and rimsulfuron showed concentration-dependent inhibition of H33342 excretion in rbABCG2-transduced MDCKII cells. To further evaluate the role of rbABCG2 in pesticide transport across the placenta barrier, we generated polarized MDCKII-rbABCG2 monolayers. Confocal microscopy confirmed correct localization of rbABCG2 protein in the apical plasma membrane. In transepithelial flux studies, we showed the time-dependent preferential basolateral to apical (B > A) directed transport of [{sup 14}C] CPF across polarized MDCKII-rbABCG2 monolayers which was significantly inhibited by the ABCG2 inhibitor fumitremorgin C (FTC). Using this novel in vitro cell culture model, we altogether showed functional secretory activity of the ABCG2 transporter from rabbit placenta and identified several pesticides like the insecticide CPF as potential rbABCG2 substrates. - Highlights: • Generation of MDCKII-rbABCG2 monolayers with epithelial barrier function • Detection of rbABCG2 in the apical plasma membrane of polarized MDCKII cells • Several pesticides interact with the ABCG2 transporter from rabbit placenta. • rbABCG2 mediates transport of the insecticide chlorpyrifos. • MDCKII-rbABCG2 cells are a suitable model to study transport in rabbit placenta.« less

Transarterial venous sinus occlusion of dural arteriovenous fistulas using ONYX.

PubMed

Torok, Collin M; Nogueira, Raul G; Yoo, Albert J; Leslie-Mazwi, Thabele M; Hirsch, Joshua A; Stapleton, Christopher J; Patel, Aman B; Rabinov, James D

2016-12-01

The purpose of this article is to present a case series of transarterial venous sinus occlusion for dural arteriovenous fistulas (DAVFs) of the transverse and sigmoid sinuses. From 2006 to 2012, 11 patients with DAVF of the transverse and sigmoid sinuses were treated with transarterial closure of the affected venous sinus using ethylene vinyl alcohol copolymer (ONYX). The consecutive retrospective cohort included six female and five male patients with an age range of 30-79. Patients presented with stroke, intracranial hemorrhage, seizure, headache, focal neurologic deficit or cognitive change. Lesions were categorized as Cognard II a + b (n = 5) or Cognard II b (n = 6). Four of this latter group consisted of isolated sinus segments. Selection criteria for dural sinus occlusion included direct multi-hole fistulas involving a broad surface in length or circumference of the sinus wall. External carotid artery (ECA) branches were directly embolized when considered safe. High-risk arterial supply from ICA, PICA, AICA or ECA cranial nerve branches were closed via retrograde approach during sinus occlusion. DAVF closure was accomplished in all 11 patients with a total of 17 embolization procedures using ONYX. High-risk arterial collaterals were closed via artery-artery or artery-sinus-artery embolization. The vein of Labbe was spared in the four cases with initial antegrade flow. No neurologic complications occurred, and DAVF closures were durable on three-month angiography. Transarterial closure of the transverse and sigmoid sinuses. © The Author(s) 2016.

Correlation between presumed sinusitis-induced pain and paranasal sinus computed tomographic findings.

PubMed

Mudgil, Shikha P; Wise, Scott W; Hopper, Kenneth D; Kasales, Claudia J; Mauger, David; Fornadley, John A

2002-02-01

The correlation between facial and/or head pain in patients clinically suspected of having sinusitis and actual localized findings on sinus computed tomographic (CT) imaging are poorly understood. To prospectively evaluate the relationship of paranasal sinus pain symptoms with CT imaging. Two hundred consecutive patients referred by otolaryngologists and internists for CT of the paranasal sinuses participated by completing a questionnaire immediately before undergoing CT. Three radiologists blinded to the patients' responses scored the degree of air/fluid level, mucosal thickening, bony reaction, and mucus retention cysts using a graded scale of severity (0 to 3 points). The osteomeatal complexes and nasolacrimal ducts were also evaluated for patency. Bivariate analysis was performed to evaluate the relationship between patients' localized symptoms and CT findings in the respective sinus. One hundred sixty-three patients (82%) reported having some form of facial pain or headache. The right temple/forehead was the most frequently reported region of maximal pain. On CT imaging the maxillary sinus was the most frequently involved sinus. Bivariate analysis failed to show any relationship between patient symptoms and findings on CT. Patients with a normal CT reported a mean 5.88 sites of facial or head pain versus 5.45 sites for patients with an abnormal CT. Patient-based responses of sinonasal pain symptoms fail to correlate with findings in the respective sinuses. CT should therefore be reserved for delineating the anatomy and degree of sinus disease before surgical intervention.

Challenges associated with reentry maxillary sinus augmentation.

PubMed

Mardinger, Ofer; Moses, Ofer; Chaushu, Gavriel; Manor, Yifat; Tulchinsky, Ze'ev; Nissan, Joseph

2010-09-01

This study was a retrospective assessment of reentry sinus augmentation compared with sinus augmentation performed for the first time. There were 38 subjects who required sinus augmentation. The study group (17 patients, 21 sinuses) included subjects following failure of a previous sinus augmentation procedure that required reentry augmentation. The control group (21 patients, 21 sinuses) included subjects in which sinus augmentation was performed for the first time. Patients' medical files were reviewed. A preformed questionnaire was used to collect data regarding demographic parameters, medical and dental health history, habits, and intra- and postoperative data. Operative challenges in the study group included adhesions of the buccal flap to the Schneiderian membrane (62%, 13/21, P<.001), bony fenestration of the lateral wall with adhesions (71%, 15/21, P<.001), limited mobility of a clinical fibrotic Schneiderian membrane (71%, 15/21, P<.001), and increased incidence of membrane perforations (47%, 10/21, versus 9.5%, 2/21, P=.03). In the control group the Schneiderian membrane was thin and flexible. Sinus augmentation succeeded in all cases of both groups. Implant failure was significantly higher in the study group (11% versus 0%, P<.001). Clinical success of reentry sinus augmentation is predictable despite its complexity. Clinicians should be aware of anatomical changes caused by previous failure of this procedure. Patients should be informed about the lower success rate of implants when reentry sinus augmentation is required. Copyright (c) 2010 Mosby, Inc. All rights reserved.

Beyond the sniffer: frontal sinuses in Carnivora.

PubMed

Curtis, Abigail A; Van Valkenburgh, Blaire

2014-11-01

Paranasal sinuses are some of the most poorly understood features of mammalian cranial anatomy. They are highly variable in presence and form among species, but their function is not well understood. The best-supported explanations for the function of sinuses is that they opportunistically fill mechanically unnecessary space, but that in some cases, sinuses in combination with the configuration of the frontal bone may improve skull performance by increasing skull strength and dissipating stresses more evenly. We used CT technology to investigate patterns in frontal sinus size and shape disparity among three families of carnivores: Canidae, Felidae, and Hyaenidae. We provide some of the first quantitative data on sinus morphology for these three families, and employ a novel method to quantify the relationship between three-dimensional sinus shape and skull shape. As expected, frontal sinus size and shape were more strongly correlated with frontal bone size and shape than with the morphology of the skull as a whole. However, sinus morphology was also related to allometric differences among families that are linked to biomechanical function. Our results support the hypothesis that frontal sinuses most often opportunistically fill space that is mechanically unnecessary, and they can facilitate cranial shape changes that reduce stress during feeding. Moreover, we suggest that the ability to form frontal sinuses allows species to modify skull function without compromising the performance of more functionally constrained regions such as the nasal chamber (heat/water conservation, olfaction), and braincase (housing the brain and sensory structures). © 2014 Wiley Periodicals, Inc.

Frequency, location, and association with dental pathology of mucous retention cysts in the maxillary sinus. A radiographic study using cone beam computed tomography (CBCT).

PubMed

Yeung, Andy Wai Kan; Tanaka, Ray; Khong, Pek-Lan; von Arx, Thomas; Bornstein, Michael M

2018-04-01

The purpose of the present study was to evaluate the frequency, locations, and dimensions of mucous retention cysts of the maxillary sinus and analyze potential associated dental pathology. A total of 156 cone beam computed tomography (CBCT) scans were included in the analysis, resulting in an evaluation of 310 maxillary sinuses. The presence of mucous retention cysts (MRC) manifesting as dome-shaped radiopacities in the sinus was diagnosed. Their locations were recorded, and dimensions (mm) were measured in coronal and sagittal/axial slices. The patients were grouped into (a) patients/sinuses with MRCs (test), and (b) patients/sinuses with healthy or any other changes (control) for further comparison and evaluation. There were 40 sinuses (12.9%) with a presence of a total of 56 MRCs. The mean age of involved patients was 29.0 years. The analysis showed that gender, age, sinus side, status of dentition, endodontic status, and periodontal status did not have a significant influence on the presence of MRCs when compared between test and control groups. Age and endodontic status exhibited a significant association with cyst location. Most of the sinuses analyzed (79.5%) did not present any MRC, and only 28.6% of the cysts diagnosed were found on the floor of the maxillary sinus. The mean dimension of the MRCs measured 6.28 ± 2.93 mm. No influencing factors on the presence or absence of MRCs were found in the present study. Most MRCs were not located on the floor of maxillary sinus. Future studies should assess their impact on surgical interventions in the sinus.

A comparative study of the incidence of Schneiderian membrane perforations during maxillary sinus augmentation with a sonic oscillating handpiece versus a conventional turbine handpiece.

PubMed

Geminiani, Alessandro; Weitz, Daniel S; Ercoli, Carlo; Feng, Changyong; Caton, Jack G; Papadimitriou, Dimitrios E V

2015-04-01

Sonic instruments may reduce perforation rates of the schneiderian membrane during lateral window sinus augmentation procedures. This study compares the incidence of membrane perforations using a sonic handpiece with an oscillating diamond insert versus a turbine handpiece with a conventional rotary diamond stone during lateral window sinus augmentation procedures. A retrospective chart analysis identified all lateral window sinus augmentation procedures done during a defined period. Among these procedures, those performed with a sonic handpiece and an oscillating diamond insert (experimental) and those performed with a conventional turbine and rotary diamond stone (conventional) were selected for this study. Reported occurrences of sinus membrane perforations during preparation of the osteotomy and elevation of the sinus membrane, as well as postoperative complications, were recorded and compared between treatment groups. Ninety-three consecutive patients were identified for a total of 130 sinus augmentation procedures (51 conventional, 79 experimental). Schneiderian membrane perforations were noted during preparation of the lateral window osteotomy in 27.5% of the sinuses in the conventional group and 12.7% of sinuses in the experimental group. During membrane elevation, perforations were noted in 43.1% of the sinuses in the conventional group and 25.3% of sinuses in the experimental group. Both differences in perforation rates were statistically significant (p < .05). There was no statistically significant difference in postoperative complications. In this study, the use of a sonic instrument to prepare the lateral window osteotomy during sinus elevation procedures resulted in a reduced perforation rate of the Schneiderian membrane compared with the conventional turbine instrument. © 2013 Wiley Periodicals, Inc.

Computed tomography-based volumetric tool for standardized measurement of the maxillary sinus

PubMed Central

Giacomini, Guilherme; Pavan, Ana Luiza Menegatti; Altemani, João Mauricio Carrasco; Duarte, Sergio Barbosa; Fortaleza, Carlos Magno Castelo Branco; Miranda, José Ricardo de Arruda

2018-01-01

Volume measurements of maxillary sinus may be useful to identify diseases affecting paranasal sinuses. However, literature shows a lack of consensus in studies measuring the volume. This may be attributable to different computed tomography data acquisition techniques, segmentation methods, focuses of investigation, among other reasons. Furthermore, methods for volumetrically quantifying the maxillary sinus are commonly manual or semiautomated, which require substantial user expertise and are time-consuming. The purpose of the present study was to develop an automated tool for quantifying the total and air-free volume of the maxillary sinus based on computed tomography images. The quantification tool seeks to standardize maxillary sinus volume measurements, thus allowing better comparisons and determinations of factors that influence maxillary sinus size. The automated tool utilized image processing techniques (watershed, threshold, and morphological operators). The maxillary sinus volume was quantified in 30 patients. To evaluate the accuracy of the automated tool, the results were compared with manual segmentation that was performed by an experienced radiologist using a standard procedure. The mean percent differences between the automated and manual methods were 7.19% ± 5.83% and 6.93% ± 4.29% for total and air-free maxillary sinus volume, respectively. Linear regression and Bland-Altman statistics showed good agreement and low dispersion between both methods. The present automated tool for maxillary sinus volume assessment was rapid, reliable, robust, accurate, and reproducible and may be applied in clinical practice. The tool may be used to standardize measurements of maxillary volume. Such standardization is extremely important for allowing comparisons between studies, providing a better understanding of the role of the maxillary sinus, and determining the factors that influence maxillary sinus size under normal and pathological conditions. PMID:29304130

Cone-Beam Computed Tomography Analysis of Mucosal Thickening in Unilateral Cleft Lip and Palate Maxillary Sinuses.

PubMed

Kula, Katherine; Hale, Lindsay N; Ghoneima, Ahmed; Tholpady, Sunil; Starbuck, John M

2016-11-01

  To compare maxillary mucosal thickening and sinus volumes of unilateral cleft lip and palate subjects (UCLP) with noncleft (nonCLP) controls.   Randomized, retrospective study of cone-beam computed tomographs (CBCT).   University.   Fifteen UCLP subjects and 15 sex- and age-matched non-CLP controls, aged 8 to 14 years.   Following institutional review board approval and reliability tests, Dolphin three-dimensional imaging software was used to segment and slice maxillary sinuses on randomly selected CBCTs. The surface area (SA) of bony sinus and airspace on all sinus slices was determined using Dolphin and multiplied by slice thickness (0.4 mm) to calculate volume. Mucosal thickening was the difference between bony sinus and airspace volumes. The number of slices with bony sinus and airspace outlines was totaled. Right and left sinus values for each group were pooled (t tests, P > .05; n = 30 each group). All measures were compared (principal components analysis, multivariate analysis of variance, analysis of variance) by group and age (P ≤ .016 was considered significant).   Principal components analysis axis 1 and 2 explained 89.6% of sample variance. Principal components analysis showed complete separation based on the sample on axis 1 only. Age groups showed some separation on axis 2. Unilateral cleft lip and palate subjects had significantly smaller bony sinus and airspace volumes, fewer bony and airspace slices, and greater mucosal thickening and percentage mucosal thickening when compared with controls. Older subjects had significantly greater bony sinus and airspace volumes than younger subjects.   Children with UCLP have significantly more maxillary sinus mucosal thickening and smaller sinuses than controls.

Hepatocyte Growth Factor Gene-Modified Mesenchymal Stem Cells Augment Sinonasal Wound Healing

PubMed Central

Li, Jing; Li, Yong; Yang, Chen; Lin, Hai; Duan, Hong-Gang

2015-01-01

This study was designed to investigate the effects of hepatocyte growth factor (HGF) transgenic mesenchymal stem cells (HGF-MSCs) on wound healing in the sinonasal mucosa and nasal epithelial cells (NECs). We also sought to determine whether HGF-MSCs and MSCs can migrate into the injured mucosa and differentiate into ciliated cells. Human HGF-overexpressing umbilical cord MSCs (hHGF-UCMSCs) were established, and upregulation of hHGF expression was confirmed by real-time PCR (RT-PCR) and enzyme-linked immunosorbant assay (ELISA). To investigate the paracrine effect of human MSCs (hMSCs) on nasal epithelial repair, hMSC- and HGF-MSC-conditioned media (CM) were used in NEC proliferation assays and in an in vitro scratch-wound repair model. The in vivo sinonasal wound-healing model was established, and all enrolled rabbits were randomly assigned to four groups: the GFP-MSC group, the HGF-MSC group, the Ad-HGF group, and the surgery control group. The average decreased diameter was recorded, and the medial wall of the maxillary sinus was removed for histological analysis and scanning electron microscopy. Collagen deposition in the wound tissue was detected via Masson trichrome (M&T) staining. The distribution of MSCs and HGF-MSCs was observed by immunofluorescence. MSCs improved nasal wound healing both in vivo and in vitro. HGF overexpression in MSCs augmented the curative effects. Reduced collagen deposition and transforming growth factor beta1 (TGF-β1) expression were detected in the HGF-MSC group compared with the MSC-, Ad-HGF-, and phosphate-buffered saline-treated groups based on M&T staining and ELISA. The enhanced therapeutic effects of HGF-MSCs were accompanied by decreased level of the fibrogenic cytokine TGF-β1. In addition, both HGF-MSCs and MSCs can migrate to the injured mucosa and epithelial layer. PMID:25835956

Hepatocyte Growth Factor Gene-Modified Mesenchymal Stem Cells Augment Sinonasal Wound Healing.

PubMed

Li, Jing; Zheng, Chun-Quan; Li, Yong; Yang, Chen; Lin, Hai; Duan, Hong-Gang

2015-08-01

This study was designed to investigate the effects of hepatocyte growth factor (HGF) transgenic mesenchymal stem cells (HGF-MSCs) on wound healing in the sinonasal mucosa and nasal epithelial cells (NECs). We also sought to determine whether HGF-MSCs and MSCs can migrate into the injured mucosa and differentiate into ciliated cells. Human HGF-overexpressing umbilical cord MSCs (hHGF-UCMSCs) were established, and upregulation of hHGF expression was confirmed by real-time PCR (RT-PCR) and enzyme-linked immunosorbant assay (ELISA). To investigate the paracrine effect of human MSCs (hMSCs) on nasal epithelial repair, hMSC- and HGF-MSC-conditioned media (CM) were used in NEC proliferation assays and in an in vitro scratch-wound repair model. The in vivo sinonasal wound-healing model was established, and all enrolled rabbits were randomly assigned to four groups: the GFP-MSC group, the HGF-MSC group, the Ad-HGF group, and the surgery control group. The average decreased diameter was recorded, and the medial wall of the maxillary sinus was removed for histological analysis and scanning electron microscopy. Collagen deposition in the wound tissue was detected via Masson trichrome (M&T) staining. The distribution of MSCs and HGF-MSCs was observed by immunofluorescence. MSCs improved nasal wound healing both in vivo and in vitro. HGF overexpression in MSCs augmented the curative effects. Reduced collagen deposition and transforming growth factor beta1 (TGF-β1) expression were detected in the HGF-MSC group compared with the MSC-, Ad-HGF-, and phosphate-buffered saline-treated groups based on M&T staining and ELISA. The enhanced therapeutic effects of HGF-MSCs were accompanied by decreased level of the fibrogenic cytokine TGF-β1. In addition, both HGF-MSCs and MSCs can migrate to the injured mucosa and epithelial layer.

Systematic Characterization and Comparative Analysis of the Rabbit Immunoglobulin Repertoire

PubMed Central

Lavinder, Jason J.; Hoi, Kam Hon; Reddy, Sai T.; Wine, Yariv; Georgiou, George

2014-01-01

Rabbits have been used extensively as a model system for the elucidation of the mechanism of immunoglobulin diversification and for the production of antibodies. We employed Next Generation Sequencing to analyze Ig germline V and J gene usage, CDR3 length and amino acid composition, and gene conversion frequencies within the functional (transcribed) IgG repertoire of the New Zealand white rabbit (Oryctolagus cuniculus). Several previously unannotated rabbit heavy chain variable (VH) and light chain variable (VL) germline elements were deduced bioinformatically using multidimensional scaling and k-means clustering methods. We estimated the gene conversion frequency in the rabbit at 23% of IgG sequences with a mean gene conversion tract length of 59±36 bp. Sequencing and gene conversion analysis of the chicken, human, and mouse repertoires revealed that gene conversion occurs much more extensively in the chicken (frequency 70%, tract length 79±57 bp), was observed to a small, yet statistically significant extent in humans, but was virtually absent in mice. PMID:24978027

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.

Antibody production in rabbits administered Freund's complete adjuvant and carprofen concurrently.

PubMed

Fishback, Joanna E; Stronsky, Sabrina M; Green, Catherine A; Bean, Krystal D; Froude, Jeffrey W

2016-02-01

Freund's complete adjuvant (FCA) is a commonly used immunopotentiator that can boost polyclonal antibody production in animal models such as rabbits, but FCA is also known to cause inflammation and pain. It is important to balance the welfare of animals with the goal of efficiently producing antibodies, but little is known about how common treatments for pain and inflammation, such as non-steroidal anti-inflammatory drugs (NSAIDs), affect the production of polyclonal antibodies. The purpose of this study was to measure polyclonal antibody production in rabbits that were administered FCA either with or without a concurrent treatment of a NSAID, carprofen. Rabbits were divided into two groups and were administered identical treatments of an antigen with adjuvant, and the treatment group also received carprofen injections at different stages of the study. Carprofen treatment did not significantly affect polyclonal antibody production, which suggests that carprofen and other NSAIDs can be used alongside FCA in rabbits to achieve desired levels of antibody production while minimizing pain and distress associated with the use of FCA.

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.

Rabbit models for biomedical research revisited via genome editing approaches

PubMed Central

HONDA, Arata; OGURA, Atsuo

2017-01-01

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

Topical Drug Delivery in Chronic Rhinosinusitis Patients before and after Sinus Surgery Using Pulsating Aerosols

PubMed Central

Möller, Winfried; Schuschnig, Uwe; Celik, Gülnaz; Münzing, Wolfgang; Bartenstein, Peter; Häussinger, Karl; Kreyling, Wolfgang G.; Knoch, Martin

2013-01-01

Objectives Chronic rhinosinusitis (CRS) is a common chronic disease of the upper airways and has considerable impact on quality of life. Topical delivery of drugs to the paranasal sinuses is challenging, therefore the rate of surgery is high. This study investigates the delivery efficiency of a pulsating aerosol in comparison to a nasal pump spray to the sinuses and the nose in healthy volunteers and in CRS patients before and after sinus surgery. Methods 99mTc-DTPA pulsating aerosols were applied in eleven CRSsNP patients without nasal polyps before and after sinus surgery. In addition, pulsating aerosols were studied in comparison to nasal pump sprays in eleven healthy volunteers. Total nasal and frontal, maxillary and sphenoidal sinus aerosol deposition and lung penetration were assessed by anterior and lateral planar gamma camera imaging. Results In healthy volunteers nasal pump sprays resulted in 100% nasal, non-significant sinus and lung deposition, while pulsating aerosols resulted 61.3+/-8.6% nasal deposition and 38.7% exit the other nostril. 9.7+/-2.0 % of the nasal dose penetrated into maxillary and sphenoidal sinuses. In CRS patients, total nasal deposition was 56.7+/-13.3% and 46.7+/-12.7% before and after sinus surgery, respectively (p<0.01). Accordingly, maxillary and sphenoidal sinus deposition was 4.8+/-2.2% and 8.2+/-3.8% of the nasal dose (p<0.01). Neither in healthy volunteers nor in CRS patients there was significant dose in the frontal sinuses. Conclusion In contrast to nasal pump sprays, pulsating aerosols can deliver significant doses into posterior nasal spaces and paranasal sinuses, providing alternative therapy options before and after sinus surgery. Patients with chronic lung diseases based on clearance dysfunction may also benefit from pulsating aerosols, since these diseases also manifest in the upper airways. PMID:24040372

Sinus involvement in inflammatory orbital pseudotumor.

PubMed

Eshaghian, J; Anderson, R L

1981-04-01

Orbital pseudotumor is a difficult diagnosis to establish preoperatively. The relationship between sinus disease and orbital pseudotumor is controversial. We describe two patients with unilateral proptosis, diplopia, palpable orbital masses, ocular discomfort, and sinus problems of short duration. Echographically, both had low reflective masses in the orbit and the adjacent sinuses. Roentgenograms and echograms were interpreted as showing erosion of the bony orbital wall. A presumptive diagnosis of sinus malignant neoplasm with orbital extension was made. Sinus histopathologic examination in one case and nasal histopathologic examination in the other showed chronic inflammatory changes compatible with the diagnosis of pseudotumor. At orbitotomy, one patient had vessels communicating between the orbital and sinus lesions, and both patients had irregular pitting of the bone next to the histologically proved orbital pseudotumors. The lytic erosive changes predicted preoperatively were not present. Simultaneous orbital and sinus pseudotumors seem to be a distinct clinicopathologic entity. Those concerned with the diagnosis and management of orbital disease should be aware of this entity.

A synthetic peptide vaccine directed against the 2ß2-2ß3 loop of domain 2 of protective antigen protects rabbits from inhalation anthrax.

PubMed

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

2010-09-15

The current vaccines for anthrax in the United States and United Kingdom are efficacious in the two most accepted animal models of inhalation anthrax, nonhuman primates and rabbits, but require extensive immunization protocols. We previously demonstrated that a linear determinant in domain 2 of Bacillus anthracis protective Ag (PA) is a potentially important target for an epitope-specific vaccine for anthrax, as Abs specific for this site, referred to as the loop-neutralizing determinant (LND), neutralize lethal toxin in vitro, yet are virtually absent in PA-immunized rabbits. In this study, we evaluated the immunogenicity and protective efficacy in rabbits of multiple antigenic peptides (MAPs) consisting of aa 304-319 from the LND of PA colinearly synthesized at the C terminus (T-B MAP) or N terminus (B-T MAP) with a heterologous T cell epitope from Plasmodium falciparum. Immunogenicity studies demonstrated that both MAPs elicited toxin-neutralizing Ab in rabbits. To evaluate the MAPs as potential anthrax vaccines, we immunized groups of rabbits (n = 7) with each MAP in Freund's adjuvant and then exposed all rabbits to a 200-LD(50) challenge with aerosolized spores of B. anthracis Ames strain. All seven rabbits immunized with the B-T MAP and 89% (six of seven) of rabbits immunized with the T-B MAP survived the spore challenge. Corollary studies with reference sera from human vaccinees immunized with rPA or anthrax vaccine absorbed and nonhuman primates immunized with PA revealed no detectable Ab with specificity for the LND. We conclude that a synthetic peptide vaccine targeting the LND would be a potentially efficacious vaccine for anthrax.

Changes in Sinus Membrane Thickness After Lateral Sinus Floor Elevation: A Radiographic Study.

PubMed

Makary, Christian; Rebaudi, Alberto; Menhall, Abdallah; Naaman, Nada

2016-01-01

To radiographically monitor sinus membrane swelling after lateral sinus floor elevation surgery at short and long healing periods. For 26 patients seeking posterior maxillary implant-supported reconstruction, 32 lateral sinus floor elevations were performed using Piezosurgery. Sinus membranes were grafted using synthetic calcium phosphate bone substitutes, and graft volume was measured in cubic centimeters for each case. Cone beam computed tomography (CBCT) examination was conducted preoperatively in all patients and for each grafted sinus at 1 day (n = 8), 2 days (n = 9), 3 days (n = 8), or 7 days (n = 7) after surgery. Control CBCT was then performed for all patients at 3, 6, and 12 months after surgery. Sinus membrane thickness was measured on cross-sectional CBCT images at nine standardized points per sinus, before lateral sinus floor elevation and at all postoperative examinations. Mean sinus membrane thickness was 0.73 mm before surgery, and 5 mm, 4.1 mm, 5.9 mm, and 7 mm, respectively, at 1, 2, 3, and 7 days after surgery. First week combined postoperative CBCT measurements of membrane thickness was 5.4 mm, then 1.3, 0.68, and 0.39 mm at 3, 6, and 12 months, respectively, after surgery. Membrane thickness significantly increased the first week after surgery and gradually decreased significantly at 3, 6, and 12 months in all groups (P < .001). First-week postoperative measurements showed a significant increase in membrane thickness at 3 days compared with the 1- and 2-day results (P < .001) and at 7 days compared with all other time points (P < .001). Membrane thickness at 2 days did not change significantly compared with 1-day measurements. Larger graft volume was positively correlated with an increase in membrane thickness after surgery at all time points (n = 32; r = 0.527; P < .001). After lateral sinus floor elevation surgery, transient swelling of sinus membrane is observed. It reaches a peak value 7 days after surgery and completely resolves over months. This swelling is correlated to the extent of sinus floor elevation.

In Vivo Performance of Bilayer Hydroxyapatite Scaffolds for Bone Tissue Regeneration in the Rabbit Radius

DTIC Science & Technology

2011-02-02

no treatments and the pres- ence of periosteal callus-like layer surrounding defects with scaffold implantation were observed after 8 weeks post...vivo evaluation of resorbable bone graft substitutes in a rabbit tibial defect model. Biomaterials. 2004; 25(20):5037–44. 20. Lu JX, Gallur A, Flautre

[Study on the sense neuropeptides of nasal mucosa in the allergic rhinitis animal model].

PubMed

Shi, Song; Zhou, Shuimiao

2006-06-01

To explore the roles of the sense neuropeptides in allergic rhinitis by observing their changes in the nasal mucosa after cutting the nasal autonomic nervous. (1) Twelve rabbits were divided into two groups: group A (sensitized) and group B (control). Four rabbits were killed respectively in one and four weeks in group A after being sensitized . Two rabbits were killed respectively at the same time in group B. Their nasal mucosa were collected for detecting substance P (SP) and calcitonin gene-related peptide (CGRP) by immunohistochemistry. (2) Twenty-four rabbits were divided into two groups: group A (sphenopalatine nerve was cut), group B (sympathetic nerve was cut). Four rabbits were killed respectively in one, two, and four weeks in group A and B. Their nasal mucosa were collected for immunohistochemistry examination. (1) SP and CGRP were apparently higher in allergic rabbits than non-allergic ones. (2) SP and CGRP decreased apparently in one and two weeks in group A and appeared no difference in four weeks. There were no apparently difference in group B among four weeks. SP and CGRP are correlative with the occurring and developing of all allergic rhinitis.

The evaluation of the local tolerance of vaginal formulations containing dapivirine using the Slug Mucosal Irritation test and the rabbit vaginal irritation test.

PubMed

Dhondt, Marijke M M; Adriaens, Els; Roey, Jens Van; Remon, Jean Paul

2005-08-01

The purpose of this study was to evaluate the local tolerance of vaginal gels (three gels containing dapivirine, the placebo gel, and Conceptrol) with the Slug Mucosal Irritation test and to compare the results with those of the rabbit vaginal irritation test. The irritation potential on the slug mucosa was assessed by the mucus production caused by a repeated treatment for 5 successive days. Additionally, membrane damage was estimated by the protein and enzyme release. By means of a classification prediction model the formulations were classified into four irritation classes. The effect of a 10-day intravaginal application of the gels on the rabbit vaginal and cervical mucosa was evaluated by means of macroscopic and microscopic examination. The placebo and dapivirine gels induced no irritation of the slug mucosa (low mucus production and protein release, no enzyme release) and no vaginal or cervical irritation in rabbits. Conceptrol caused severe irritation of the slug mucosa (increased mucus production, protein release, and enzyme release) and irritation of the rabbit vagina and cervix. The results obtained with the Slug Mucosal Irritation test were comparable to those of the rabbit vaginal irritation test.

JBP485 promotes tear and mucin secretion in ocular surface epithelia

PubMed Central

Nakamura, Takahiro; Hata, Yuiko; Nagata, Maho; Yokoi, Norihiko; Yamaguchi, Shumpei; Kaku, Taiichi; Kinoshita, Shigeru

2015-01-01

Dry eye syndrome (DES), a multifactorial disease of the tears and ocular surface, is one of the most common ocular disorders. Tear film contains ocular mucins and is essential for maintaining the homeostasis of the wet ocular surface. Since there are a limited number of clinical options for the treatment of DES, additional novel treatments are needed to improve the clinical results. In this study, we found that placental extract-derived dipeptide (JBP485) clearly promoted the expression and secretion of gel-forming mucin 5ac (Muc5ac) in rabbit conjunctival epithelium. JBP485 also elevated the expression level of cell surface-associated mucins (Muc1/4/16) in rabbit corneal epithelium. The Schirmer tear test results indicated that JBP485 induced tear secretion in the rabbit model. Moreover, JBP485 clinically improved corneal epithelial damage in a mouse dry eye model. Thus, our data indicate that JBP485 efficiently promoted mucin and aqueous tear secretion in rabbit ocular surface epithelium and has the potential to be used as a novel treatment for DES. PMID:25996902

JBP485 promotes tear and mucin secretion in ocular surface epithelia.

PubMed

Nakamura, Takahiro; Hata, Yuiko; Nagata, Maho; Yokoi, Norihiko; Yamaguchi, Shumpei; Kaku, Taiichi; Kinoshita, Shigeru

2015-05-21

Dry eye syndrome (DES), a multifactorial disease of the tears and ocular surface, is one of the most common ocular disorders. Tear film contains ocular mucins and is essential for maintaining the homeostasis of the wet ocular surface. Since there are a limited number of clinical options for the treatment of DES, additional novel treatments are needed to improve the clinical results. In this study, we found that placental extract-derived dipeptide (JBP485) clearly promoted the expression and secretion of gel-forming mucin 5ac (Muc5ac) in rabbit conjunctival epithelium. JBP485 also elevated the expression level of cell surface-associated mucins (Muc1/4/16) in rabbit corneal epithelium. The Schirmer tear test results indicated that JBP485 induced tear secretion in the rabbit model. Moreover, JBP485 clinically improved corneal epithelial damage in a mouse dry eye model. Thus, our data indicate that JBP485 efficiently promoted mucin and aqueous tear secretion in rabbit ocular surface epithelium and has the potential to be used as a novel treatment for DES.

Influence of Micro Threads Alteration on Osseointegration and Primary Stability of Implants: An FEA and In Vivo Analysis in Rabbits.

PubMed

Chowdhary, Ramesh; Halldin, Anders; Jimbo, Ryo; Wennerberg, Ann

2015-06-01

To describe the early bone tissue response to implants with and without micro threads designed to the full length of an oxidized titanium implant. A pair of two-dimensional finite element models was designed using a computer aided three-dimensional interactive application files of an implant model with micro threads in between macro threads and one without micro threads. Oxidized titanium implants with (test implants n=20) and without (control implants n=20) micro thread were prepared. A total of 12 rabbits were used and each received four implants. Insertion torque while implant placement and removal torque analysis after 4 weeks was performed in nine rabbits, and histomorphometric analysis in three rabbits, respectively. Finite element analysis showed less stress accumulation in test implant models with 31Mpa when compared with 62.2 Mpa in control implant model. Insertion and removal torque analysis did not show any statistical significance between the two implant designs. At 4 weeks, there was a significant difference between the two groups in the percentage of new bone volume and bone-to-implant contact in the femur (p< .05); however, not in the tibia. The effect of micro threads was prominent in the femur suggesting that micro threads promote bone formation. The stress distribution supported by the micro threads was especially effective in the cancellous bone. © 2013 Wiley Periodicals, Inc.

Sphenoid sinus mucocele as a cause of isolated pupil-sparing oculomotor nerve palsy mimicking diabetic ophthalmoplegia.

PubMed

Mohebbi, Alireza; Jahandideh, Hesam; Harandi, Ali Amini

2013-12-01

A 37-year-old woman presented with isolated right-sided oculomotor nerve palsy. Neurologic examination revealed no other disorder. Computed tomography of the paranasal sinuses demonstrated complete opacification of the sphenoid sinus. Dense mucoid fluid was drained from the sphenoid sinus via an endoscopic transseptal sphenoidotomy. A biopsy confirmed the diagnosis of sphenoid sinus mucocele. At follow-up 4 weeks postoperatively, the patient's ocular symptoms were markedly alleviated. Considering rare causes of isolated oculomotor nerve palsy, such as sphenoid sinus mucocele, is important in the differential diagnosis, even in patients with well-known risk factors such as diabetes mellitus.

Odontogenic sinus tracts: a cohort study.

PubMed

Slutzky-Goldberg, Iris; Tsesis, Igor; Slutzky, Hagay; Heling, Ilana

2009-01-01

To determine the prevalence,location, and distribution of sinus tracts in patients referred for endodontic consultation. This cohort study included 1,119 subjects referred for endodontic consultation, 108 of whom presented with sinus tracts. Following clinical and radiographic examination, the diameter of the rarifying osteitis lesion on the radiograph was measured and the path and origin of the sinus tracts determined. Signs and symptoms, tooth site,buccal/lingual location, and diameter were recorded. Data were statistically analyzed using Pearson chi-square test. Sinus tracts originated mainly from maxillary teeth (63.1%); only 38.9% originated from mandibular teeth. Chronic periapical abscess was the most prevalent diagnosed origin (71.0%). Broken restorations were highly associated with the presence of sinus tracts (53.0%). The most frequent site of orifices was buccal(82.4%), followed by lingual or palatal (12.0%). Orifices on the lingual aspect of the gingiva were observed in mandibularmolars. There was an 86.8% correlation between the occurrence of an apically located sinus tract and apical rarifying osteitis(P<.01). Sinus tract in the lingual or palatal aspect of the gingiva is relatively common. Practitioners should look for signs of sinus tract during routine examination

Development of the ethmoid sinus and extramural migration: the anatomical basis of this paranasal sinus.

PubMed

Márquez, Samuel; Tessema, Belachew; Clement, Peter Ar; Schaefer, Steven D

2008-11-01

Frontal and/or maxillary sinusitis frequently originates with pathologic processes of the ethmoid sinuses. This clinical association is explained by the close anatomical relationship between the frontal and maxillary sinuses and the ethmoid sinus, since developmental trajectories place the ethmoid in a strategic central position within the nasal complex. The advent of optical endoscopes has permitted improved visualization of these spaces, leading to a renaissance in intranasal sinus surgery. Advancing patient care has consequently driven the need for the proper and accurate anatomical description of the paranasal sinuses, regrettably the continuing subject of persistent confusion and ambiguity in nomenclature and terminology. Developmental tracking of the pneumatization of the ethmoid and adjacent bones, and particularly of the extramural cells of the ethmoid, helps to explain the highly variable adult morphology of the ethmoid air sinus system. To fully understand the nature and underlying biology of this sinus system, multiple approaches were employed here. These include CT imaging of living humans (n = 100), examination of dry cranial material (n = 220), fresh tissue and cadaveric anatomical dissections (n = 168), and three-dimensional volume rendering methods that allow digitizing of the spaces of the ethmoid sinus for graphical examination. Results show the ethmoid sinus to be highly variable in form and structure as well as in the quantity of air cells. The endochondral bony origin of the ethmoid sinuses leads to remarkably thin bony contours of their irregular and morphologically unique borders, making them substantially different from the other paranasal sinuses. These investigations allow development of a detailed anatomical template of this region based on observed patterns of morphological diversity, which can initially mask the underlying anatomy. For example, the frontal recess, ethmoid infundibulum, and hiatus semilunaris are key anatomical components of the ethmoid structural complex that are fully documented and explained here on the basis of the template we have developed, as well as being comprehensively illustrated. In addition, an exhaustive 2000-year literature search identified original sources of nomenclature, in order to help clarify the persistent confusions found in the literature. Modified anatomical terms are suggested to permit proper description of the ethmoid region. This clarification of nomenclature will permit better communication in addition to eliminating redundant terminology. The combination of anatomical, evolutionary, and clinical perspectives provides an important strategy for gaining insight into the complexity of these sinuses. Copyright 2008 Wiley-Liss, Inc.

Is 'sinus' pain really sinusitis?

PubMed

Agius, A M; Jones, N S; Muscat, R

2014-10-01

So-called 'sinus pain' is a common complaint in GP and ear, nose and throat clinics, and patients often receive treatment with antibiotics and decongestants. Recent evidence suggests that facial pain may not be related to the sinuses at all and that doctors may have to rethink their prescribing strategy.

Cetuximab and Everolimus in Treating Patients With Metastatic or Recurrent Colon Cancer or Head and Neck Cancer

ClinicalTrials.gov

2012-07-06

Recurrent Adenoid Cystic Carcinoma of the Oral Cavity; Recurrent Basal Cell Carcinoma of the Lip; Recurrent Colon Cancer; Recurrent Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Recurrent Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Recurrent Lymphoepithelioma of the Nasopharynx; Recurrent Lymphoepithelioma of the Oropharynx; Recurrent Metastatic Squamous Neck Cancer With Occult Primary; Recurrent Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Recurrent Mucoepidermoid Carcinoma of the Oral Cavity; Recurrent Salivary Gland Cancer; Recurrent Squamous Cell Carcinoma of the Hypopharynx; Recurrent Squamous Cell Carcinoma of the Larynx; Recurrent Squamous Cell Carcinoma of the Lip and Oral Cavity; Recurrent Squamous Cell Carcinoma of the Nasopharynx; Recurrent Squamous Cell Carcinoma of the Oropharynx; Recurrent Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Recurrent Verrucous Carcinoma of the Larynx; Recurrent Verrucous Carcinoma of the Oral Cavity; Stage IV Adenoid Cystic Carcinoma of the Oral Cavity; Stage IV Basal Cell Carcinoma of the Lip; Stage IV Lymphoepithelioma of the Nasopharynx; Stage IV Lymphoepithelioma of the Oropharynx; Stage IV Mucoepidermoid Carcinoma of the Oral Cavity; Stage IV Squamous Cell Carcinoma of the Hypopharynx; Stage IV Squamous Cell Carcinoma of the Larynx; Stage IV Squamous Cell Carcinoma of the Lip and Oral Cavity; Stage IV Squamous Cell Carcinoma of the Nasopharynx; Stage IV Squamous Cell Carcinoma of the Oropharynx; Stage IV Verrucous Carcinoma of the Larynx; Stage IV Verrucous Carcinoma of the Oral Cavity; Stage IVA Colon Cancer; Stage IVA Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IVA Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage IVA Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage IVA Salivary Gland Cancer; Stage IVA Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Colon Cancer; Stage IVB Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IVB Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage IVB Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage IVB Salivary Gland Cancer; Stage IVB Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Esthesioneuroblastoma of the Paranasal Sinus and Nasal Cavity; Stage IVC Inverted Papilloma of the Paranasal Sinus and Nasal Cavity; Stage IVC Midline Lethal Granuloma of the Paranasal Sinus and Nasal Cavity; Stage IVC Salivary Gland Cancer; Stage IVC Squamous Cell Carcinoma of the Paranasal Sinus and Nasal Cavity; Tongue Cancer

Subchronic (26- and 52-week) toxicity and irritation studies of a novel microbicidal gel formulation containing sodium lauryl sulfate in animal models.

PubMed

Piret, Jocelyne; Laforest, Geneviève; Bussières, Martin; Bergeron, Michel G

2008-03-01

The safety of an ethylene oxide/propylene oxide gel formulation containing sodium lauryl sulfate (2%, w/w), that could be a potent candidate as a topical microbicide, has been evaluated. More specifically, the subchronic (26- and 52-week) toxicity of the formulation when applied intravaginally as well as its irritating potential for the rectal, penile, eye, skin and buccal mucosa have been examined in animal models. The results showed that the vaginal administration of the gel formulation containing sodium lauryl sulfate once and twice daily (with doses 12 +/- 2 h apart) for 26 weeks to rats and for 52 weeks to rabbits induced slight to moderate histopathological alterations. When the formulation was applied intrarectally to male and female rabbits once and twice daily (with doses 12 +/- 2 h apart) for 14 days, no macroscopic or microscopic changes were reported. For both vaginal and rectal dosing, no effect was seen on the haematology, coagulation and serum chemistry parameters as well as on the body weight of animals and the relative organ weights. Other sporadic macroscopic and histopathological findings were incidental in origin and of no toxicological significance. The gel formulation containing sodium lauryl sulfate was considered as mildly irritating for the penile mucosa of rabbits, non-irritating for the eye of rabbits, mildly irritating for the skin in a rabbit model and non-irritating for the hamster cheek pouch. It is suggested that the gel formulation containing sodium lauryl sulfate is safe for most tissues that could be exposed to the product under normal use.

Refined methods to evaluate the in vivo hemostatic function and viability of transfused human platelets in rabbit models.

PubMed

Watanabe, Naohide; Nogawa, Masayuki; Ishiguro, Mariko; Maruyama, Hitomi; Shiba, Masayuki; Satake, Masahiro; Eto, Koji; Handa, Makoto

2017-08-01

To bridge the gap between in vitro function and clinical efficacy of platelet (PLT) transfusion products, reliable in vivo PLT functional assays for hemostasis and survival in animal models are required. However, there are no standardized methods for assessing the in vivo quality of transfused human PLTs. Plasma-depleted human PLT concentrates (PCs; Day 3, Day 5, Day 7, Day 10, and damaged) were transfused into busulfan-induced rabbits with thrombocytopenia with prolonged bleeding times 1 day after treatment with ethyl palmitate (EP) to block their reticuloendothelial systems. The hemostatic effect of PC transfusion was evaluated by the ear fine vein bleeding time. For the in vivo survival assay, splenectomized EP-treated rabbits were transfused with human PCs, and viability of the human PLTs in the rabbits was determined by flow cytometry using human PLT-specific antibodies and Trucount tubes. The hemostatic effect of PCs was slightly reduced with increasing storage periods for early time points, but more dramatically reduced for later time points. PLT survival was similar after 3 and 7 days of storage, but PLTs stored for 10 days showed significantly poorer survival than those stored only 3 days. Our new and improved protocol for in vivo assessment of transfused PLTs is sufficiently sensitive to detect subtle changes in hemostatic function and viability of human PLTs transfused into rabbit models. This protocol could contribute to preclinical in vivo functional assessment and clinical quality assurance of emerging novel PLT products such as cultured cell-derived human PLTs. © 2017 AABB.

Angiogenesis and bone regeneration by allogeneic mesenchymal stem cell intravenous transplantation in rabbit model of avascular necrotic femoral head.

PubMed

Li, Zhanghua; Liao, Wen; Zhao, Qiang; Liu, Ming; Xia, Wei; Yang, Yi; Shao, Ningsheng

2013-07-01

To explore the feasibility of allogeneic mesenchymal stem cells (MSCs) transplanted intravenously for angiogenesis and bone repair in a rabbit model of avascular necrosis of femoral head (ANFH). Forty-five rabbits were randomized into three groups: a blank control group (without treatment), a necrotic control group (ANFH induced but without therapy), and an MSC transplantation group (ANFH induced and treated with MSC transplantation). The biopsies, blood sampling, and imaging examinations were performed on each animal at different time points (2, 4, and 6 wk). To monitor angiogenesis and bone repair progress, examinations included real-time polymerase chain reaction, Western blot analysis, x-ray, computed tomography, Masson trichrome staining, picrosirius red staining, and immunohistochemical staining. Necrosis and bone collapse were observed in bilateral femoral heads of necrotic rabbits of the necrotic control group, whereas the femoral head morphology was generally restored in the MSC transplantation group. The mRNA levels of Cbfa1, BMP, VEGF, and OPN in bone tissue were significantly higher in the MSC transplantation group than in the necrotic control group. In addition, the total protein amount of Cbfa1 in the MSC transplantation group was also significantly higher than that in the necrotic control group (P < 0.05). Intravenous transplantation of allogeneic MSCs can promote vascular and bone regeneration in the necrotic region of the femoral head in a rabbit model of ANFH. The results of our study suggest that the intravenous transplantation of MSCs could be a potential and minimally invasive treatment option for ANFH patients. Copyright © 2013 Elsevier Inc. All rights reserved.

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.

Immunoproteomic Identification of In Vivo-Produced Propionibacterium acnes Proteins in a Rabbit Biofilm Infection Model

PubMed Central

Achermann, Yvonne; Tran, Bao; Kang, Misun; Harro, Janette M.

2015-01-01

Propionibacterium acnes is well-known as a human skin commensal but can also act as an invasive pathogen causing implant-associated infections. In order to resolve these types of P. acnes infections, the implants must be removed, due to the presence of an established biofilm that is recalcitrant to antibiotic therapy. In order to identify those P. acnes proteins produced in vivo during a biofilm infection, we established a rabbit model of implant-associated infection with this pathogen. P. acnes biofilms were anaerobically grown on dextran beads that were then inoculated into the left tibias of rabbits. At 4 weeks postinoculation, P. acnes infection was confirmed by radiograph, histology, culture, and PCR. In vivo-produced and immunogenic P. acnes proteins were detected on Western blot using serum samples from rabbits infected with P. acnes after these bacterial proteins were separated by two-dimensional gel electrophoresis. Those proteins that bound host antibodies were then isolated and identified by tandem mass spectrometry. Radiographs and histology demonstrated a disruption in the normal bone architecture and adherent biofilm communities in those animals with confirmed infections. A total of 24 immunogenic proteins were identified; 13 of these proteins were upregulated in both planktonic and biofilm modes, including an ABC transporter protein. We successfully adapted a rabbit model of implant-associated infection for P. acnes to identify P. acnes proteins produced during a chronic biofilm-mediated infection. Further studies are needed to evaluate the potential of these proteins for either a diagnostic test or a vaccine to prevent biofilm infections caused by P. acnes. PMID:25694647

Flow field and oscillatory shear stress in a tuning-fork-shaped model of the average human carotid bifurcation.

PubMed

Ding, Z; Wang, K; Li, J; Cong, X

2001-12-01

The oscillatory shear index (OSI) was developed based on the hypothesis that intimal hyperplasia was correlated with oscillatory shear stresses. However, the validity of the OSI was in question since the correlation between intimal thickness and the OSI at the side walls of the sinus in the Y-shaped model of the average human carotid bifurcation (Y-AHCB) was weak. The objectives of this paper are to examine whether the reason for the weak correlation lies in the deviation in geometry of Y-AHCB from real human carotid bifurcation, and whether this correlation is clearly improved in the tuning-fork-shaped model of the average human carotid bifurcation (TF-AHCB). The geometry of the TF-AHCB model was based on observation and statistical analysis of specimens from 74 cadavers. The flow fields in both models were studied and compared by using flow visualization methods under steady flow conditions and by using laser Doppler anemometer (LDA) under pulsatile flow conditions. The TF-shaped geometry leads to a more complex flow field than the Y-shaped geometry. This added complexity includes strengthened helical movements in the sinus, new flow separation zone, and directional changes in the secondary flow patterns. The results show that the OSI-values at the side walls of the sinus in the TF-shaped model were more than two times as large as those in the Y-shaped model. This study confirmed the stronger correlation between the OSI and intimal thickness in the tuning-fork geometry of human carotid bifurcation, and the TF-AHCB model is a significant improvement over the traditional Y-shaped model.

Outcomes of flapless crestal maxillary sinus elevation under hydraulic pressure.

PubMed

Bensaha, Tarik

2012-01-01

Sinus elevation through the crestal approach has become a routine procedure for implant placement in the posterior edentulous maxilla. The combination of flapless surgery and crestal sinus elevation with simultaneous placement of implants is an attractive surgical approach for implant grafting in the posterior maxilla, but its efficacy and safety have seldom been studied. The aim of this study is to evaluate retrospectively the outcomes of flapless crestal sinus floor elevation using piezosurgery and a hydraulic sinus elevation system with simultaneous implant placement. Between October 2009 and August 2010, flapless implant surgery using a crestal approach, accompanied by simultaneous hydraulic sinus elevation and grafting, was performed. Patients were followed up clinically and with intraoral and panoramic radiographs. Any postoperative complications, including swelling, discomfort, infection, fractures, and implant loss, were recorded, and sinus bone gain was measured. Thirty-one sinuses were elevated and 35 implants were placed. Patients were a mean of 41.2 ± 6.69 years old, and 45% were women. The sinus was elevated to 7 to 15 mm, and no membrane perforations were noted. The mean follow-up period was 21 weeks. The mean bone gain under the maxillary sinus was 12.03 ± 2.1 mm, and all implants displayed primary stability with a mean insertion torque ≥ 15 Ncm. No postoperative discomfort, swelling, hematoma, infection, or bone fenestration was noted. One patient experienced prolonged edema in the lower eyelid region, and another lost an implant. In this retrospective analysis, flapless crestal sinus floor elevation was safe and effective, decreasing surgical discomfort and trauma and early implant failures.

An increasing electromechanical window is a predictive marker of ventricular fibrillation in anesthetized rabbit with ischemic heart.

PubMed

Limprasutr, Vudhiporn; Pirintr, Prapawadee; Kijtawornrat, Anusak; Hamlin, Robert L

2018-05-10

The QTc interval is widely used in Safety Pharmacological studies to predict arrhythmia risk, and the electromechanical window (EMW) and short-term variability of QT intervals (STV QT ) have been studied as new biomarkers for drug-induced Torsades de Pointes (TdP). However, the use of EMW and STV QT to predict ventricular fibrillation (VF) has not been elucidated. This study aimed to evaluate EMW and STV QT to predict VF in anesthetized rabbit model of VF. VF was induced by ligation of the left anterior descending and a descending branch of the left circumflex coronary arteries in a sample population of rabbits (n=18). VF was developed 55.6% (10/18). In rabbit with VF, the EMW was significantly higher than in rabbits without VF (96.3 ± 15.6 ms and 49.5 ± 5.6 ms, respectively, P<0.05). STV QT had significantly increased before the onset of VF in rabbits that experienced VF, but not in rabbits that did not experience VF (11.7 ± 1.8 ms and 3.7 ± 0.4 ms, respectively, P<0.05). The EMW and STV QT had better predictive power for VF with higher sensitivity and specificity than the QTc measure. The result suggested that the increasing of EMW, as well as the elevation of STV QT , can potentially be used as biomarkers for predicting of VF.

Development of a Rabbit Model of Radiation-Induced Sciatic Nerve Injury: In Vivo Evaluation Using T2 Relaxation Time Measurements.

PubMed

Wan, Qi; Zeng, Qian; Li, Xinchun; Sun, Chongpeng; Zhou, Jiaxuan; Zou, Qiao; Deng, Yingshi; Niu, Daoli

2015-01-01

To develop a rabbit model of radiation-induced sciatic nerve injury (RISNI), using computed tomography (CT)-guided stereotactic radiosurgery, and assess the value of T2 measurements of injured nerves. Twenty New Zealand rabbits were randomly divided into A (n = 5) and B (n = 15) groups. Group A rabbits underwent CT and magnetic resonance scan and were then killed for comparison of images and anatomy of sciatic nerves. One side of the sciatic nerve of group B rabbits received irradiation doses of 35, 50, or 70 Gy (n = 5 per group). Magnetic resonance imaging and functional assessments were performed before irradiation and 1, 2, 3, and 4 months thereafter. The thigh section of the sciatic nerve outside the pelvis could be observed by CT and magnetic resonance imaging. T2 values of the irradiated nerve of the 35-Gy group increased gradually, peaking at 4 months; T2 values of the 50-Gy group increased faster, peaking at 3 months. Significant differences between the 35-Gy and control groups were found at 3 and 4 months, and between the 50-Gy and control groups at 2, 3, and 4 months. Functional scores of the 50-Gy group declined progressively, whereas the 35-Gy group scores reached a low point at 3 months posttreatment and then recovered. Functional scores of the irradiated limbs demonstrated a negative correlation with T2 values (r = -0.591 and -0.595, P < 0.05). Electron microscopy revealed progressive deformation and degeneration of the irradiated nerve in the 35- and 50-Gy groups, which were more severe in the 50-Gy group. A rabbit RISNI model can be produced using the midthigh segment of the sciatic nerve and single-fraction doses of 35 and 50 Gy. Although T2 values are useful for monitoring RISNI, they may not be sensitive enough to evaluate its severity.

Identification of microRNAs involved in Alzheimer’s progression using a rabbit model of the disease

PubMed Central

Liu, Qing Yan; Chang, Marilyn N Vera; Lei, Joy X; Koukiekolo, Roger; Smith, Brandon; Zhang, Dongling; Ghribi, Othman

2014-01-01

Alzheimer’s disease (AD) is the most common neurodegenerative disorder characterized by the presence of extracellular plaques of β-amyloid peptides and intracellular tangles of hyperphosphorylated tau proteins in the brain. The vast majority of cases are late onset AD (LOAD), which are genetically heterogeneous and occur sporadically. High blood cholesterol is suggested to be a risk factor for this disease. Several neuropathological changes of LOAD can be reproduced by supplementing a rabbit’s diet with 2% cholesterol for 12 weeks. Accumulating data in the literature suggest that microRNAs (miRNA) participate in the development of AD pathology. The present study focuses on the survey of changes of miRNA expression in rabbit brains during the progression of AD-like pathology using microarray followed by Taq-Man qRT-PCR analyses. Out of 1769 miRNA probes used in the experiments, 99 miRNAs were found to be present in rabbit brain, 57 were newly identified as miRNAs from rabbit brain. Eleven miRNAs showed significant changes over AD-like pathology progression. Among them, the changes of miR-125b, miR-98, miR-107, miR-30, along with 3 members of the let-7 family were similar to those observed in human AD samples, whereas the expression patterns of miR-15a, miR-26b, miR-9 and miR-576-3p were unique to this rabbit LOAD model. The significant up regulation of miR-26b is consistent with the decrease of leptin levels in the brains of cholesterol fed rabbit model for AD, confirming that miR-26b is indeed regulated by leptin and that both leptin and miR-26b may be involved in cholesterol induced AD-like pathology. PMID:24754001

The effect of rabbit age on in vitro caecal fermentation of starch, pectin, xylan, cellulose, compound feed and its fibre.

PubMed

Lavrenčič, A

2007-03-01

In vitro gas production kinetics of six different substrates, pectin (PEC), xylan (XYL), starch (STA), cellulose (CEL), commercial compound feed (FEED; 201 g crude protein per kg, 155 g crude fibre per kg, 334 g neutral-detergent fibre (NDF) per kg and 190 g acid-detergent fibre (ADF) per kg) and an NDF prepared from commercial compound feed (NDFFEED) were determined using the caecum contents of weaned rabbits (36 days of age) and of rabbits at slaughter age (78 days of age) as inoculums. The cumulated gas production over 96 h of incubation was modelled with Gompertz model, and the kinetic parameters compared. The total potential gas production (parameter 'B' of the Gompertz model) was not affected (P>0.05) by the inoculum source, except with STA, where rabbits at slaughter weight had significantly higher total potential fermentability (314 ml/g dry matter (DM)) than those at weaning age (189 ml/g DM). Intensities of fermentation (maximum fermentation rate; MFR) of PEC (32.2 ml/h) and XYL (24.4 ml/h) were significantly greater in rabbits at weaning, while that of STA (45 ml/h) was significantly lower than at slaughter age (23.0, 14.3 and 14.0 ml/h for PEC, XYL and STA, respectively). The MFRs of CEL and NDFFEED were very similar between inoculum sources. In the first 10 h of fermentation which correspond to the normal retention time of the substrates in the caecum, the highest amount of gas was produced from PEC, followed by FEED and XYL. These substrates had a time of maximum fermentation rate (TMFR) at both rabbit ages short enough (8.0 and 9.5 h for PEC, 9.5 and 6.6 h for FEED, 13.7 and 14.2 h for XYL at weaning and at slaughter age, respectively) to be almost completely fermented in vivo.

21 CFR 870.3850 - Carotid sinus nerve stimulator.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Carotid sinus nerve stimulator. 870.3850 Section... nerve stimulator. (a) Identification. A carotid sinus nerve stimulator is an implantable device used to decrease arterial pressure by stimulating Hering's nerve at the carotid sinus. (b) Classification. Class...

Nitrite therapy prevents chlorine gas toxicity in rabbits.

PubMed

Honavar, Jaideep; Doran, Stephen; Ricart, Karina; Matalon, Sadis; Patel, Rakesh P

2017-04-05

Chlorine (Cl 2 ) gas exposure and toxicity remains a concern in military and industrial sectors. While post-Cl 2 exposure damage to the lungs and other tissues has been documented and major underlying mechanisms elucidated, no targeted therapeutics that are effective when administered post-exposure, and which are amenable to mass-casualty scenarios have been developed. Our recent studies show nitrite administered by intramuscular (IM) injection post-Cl 2 exposure is effective in preventing acute lung injury and improving survival in rodent models. Our goal in this study was to develop a rabbit model of Cl 2 toxicity and test whether nitrite affords protection in a non-rodent model. Exposure of New Zealand White rabbits to Cl 2 gas (600ppm, 45min) caused significant increases in protein and neutrophil accumulation in the airways and ∼35% mortality over 18h. Nitrite administered 30min post Cl 2 exposure by a single IM injection, at 1mg/kg or 10mg/kg, prevented indices of acute lung injury at 6h by up to 50%. Moreover, all rabbits that received nitrite survived over the study period. These data provide further rationale for developing nitrite as post-exposure therapeutic to mitigate against Cl 2 gas exposure injury. Copyright © 2017 Elsevier B.V. All rights reserved.

Enhanced Tendon-to-Bone Healing of Chronic Rotator Cuff Tears by Bone Marrow Aspirate Concentrate in a Rabbit Model

PubMed Central

Liu, Xiao Ning; Yang, Cheol-Jung; Kim, Ji Eui; Du, Zhen Wu; Ren, Ming; Zhang, Wei; Zhao, Hong Yu; Kim, Kyung Ok

2018-01-01

Background To evaluate the influence of bone marrow aspirate concentrate (BMAC) on tendon-to-bone healing in a rabbit rotator cuff model and to characterize the composition of growth factors in BMAC. Methods In this in vivo study, 40 rabbits were allocated into five groups: control (C), repair + saline (RS), repair + platelet-rich plasma (PRP; RP), repair + BMAC (RB) and repair + PRP + BMAC (RPB). A tear model was created by supraspinatus tendon transection at the footprint. Six weeks after transection, the torn tendon was repaired along with BMAC or PRP administration. Six weeks after repair, shoulder samples were harvested for biomechanical and histological testing. Ten rabbits were used for processing PRP and BMAC, followed by analysis of blood cell composition and the levels of growth factors in vitro. Results The ultimate load-to-failure was significantly higher in RPB group compared to RS group (p = 0.025). BMAC-treated groups showed higher values of biomechanical properties than RS group. The histology of BMAC-treated samples showed better collagen fiber continuity and orientation than RS group. BMAC contained significantly higher levels of the several growth factors than PRP. Conclusions Locally administered BMAC enhanced tendon-to-bone healing and has potential for clinical applications. PMID:29564054

Clinical field-strength MRI of amyloid plaques induced by low-level cholesterol feeding in rabbits

PubMed Central

Chen, Yuanxin; Bernas, Lisa; Kitzler, Hagen H.; Rogers, Kem A.; Hegele, Robert A.; Rutt, Brian K.

2009-01-01

Two significant barriers have limited the development of effective treatment of Alzheimer's disease. First, for many cases the aetiology is unknown and likely multi-factorial. Among these factors, hypercholesterolemia is a known risk predictor and has been linked to the formation of β-amyloid plaques, a pathological hallmark this disease. Second, standardized diagnostic tools are unable to definitively diagnose this disease prior to death; hence new diagnostic tools are urgently needed. Magnetic resonance imaging (MRI) using high field-strength scanners has shown promise for direct visualization of β-amyloid plaques, allowing in vivo longitudinal tracking of disease progression in mouse models. Here, we present a new rabbit model for studying the relationship between cholesterol and Alzheimer's disease development and new tools for direct visualization of β-amyloid plaques using clinical field-strength MRI. New Zealand white rabbits were fed either a low-level (0.125–0.25% w/w) cholesterol diet (n = 5) or normal chow (n = 4) for 27 months. High-resolution (66 × 66 × 100 µm3; scan time = 96 min) ex vivo MRI of brains was performed using a 3-Tesla (T) MR scanner interfaced with customized gradient and radiofrequency coils. β-Amyloid-42 immunostaining and Prussian blue iron staining were performed on brain sections and MR and histological images were manually registered. MRI revealed distinct signal voids throughout the brains of cholesterol-fed rabbits, whereas minimal voids were seen in control rabbit brains. These voids corresponded directly to small clusters of extracellular β-amyloid-positive plaques, which were consistently identified as iron-loaded (the presumed source of MR contrast). Plaques were typically located in the hippocampus, parahippocampal gyrus, striatum, hypothalamus and thalamus. Quantitative analysis of the number of histologically positive β-amyloid plaques (P < 0.0001) and MR-positive signal voids (P < 0.05) found in cholesterol-fed and control rabbit brains corroborated our qualitative observations. In conclusion, long-term, low-level cholesterol feeding was sufficient to promote the formation of extracellular β-amyloid plaque formation in rabbits, supporting the integral role of cholesterol in the aetiology of Alzheimer's disease. We also present the first evidence that MRI is capable of detecting iron-associated β-amyloid plaques in a rabbit model of Alzheimer's disease and have advanced the sensitivity of MRI for plaque detection to a new level, allowing clinical field-strength scanners to be employed. We believe extension of these technologies to an in vivo setting in rabbits is feasible and that our results support future work exploring the role of MRI as a leading imaging tool for this debilitating and life-threatening disease. PMID:19293239

Cyanide Toxicokinetics: The Behavior of Cyanide, Thiocyanate and 2-Amino-2-Thiazoline-4-Carboxylic Acid in Multiple Animal Models

PubMed Central

Bhandari, Raj K.; Oda, Robert P.; Petrikovics, Ilona; Thompson, David E.; Brenner, Matthew; Mahon, Sari B.; Bebarta, Vikhyat S.; Rockwood, Gary A.; Logue, Brian A.

2014-01-01

Cyanide causes toxic effects by inhibiting cytochrome c oxidase, resulting in cellular hypoxia and cytotoxic anoxia, and can eventually lead to death. Cyanide exposure can be verified by direct analysis of cyanide concentrations or analyzing its metabolites, including thiocyanate (SCN−) and 2-amino-2-thiazoline-4-carboxylic acid (ATCA) in blood. To determine the behavior of these markers following cyanide exposure, a toxicokinetics study was performed in three animal models: (i) rats (250–300 g), (ii) rabbits (3.5–4.2 kg) and (iii) swine (47–54 kg). Cyanide reached a maximum in blood and declined rapidly in each animal model as it was absorbed, distributed, metabolized and eliminated. Thiocyanate concentrations rose more slowly as cyanide was enzymatically converted to SCN−. Concentrations of ATCA did not rise significantly above the baseline in the rat model, but rose quickly in rabbits (up to a 40-fold increase) and swine (up to a 3-fold increase) and then fell rapidly, generally following the relative behavior of cyanide. Rats were administered cyanide subcutaneously and the apparent half-life (t1/2) was determined to be 1,510 min. Rabbits were administered cyanide intravenously and the t1/2 was determined to be 177 min. Swine were administered cyanide intravenously and the t1/2 was determined to be 26.9 min. The SCN− t1/2 in rats was 3,010 min, but was not calculated in rabbits and swine because SCN− concentrations did not reach a maximum. The t1/2 of ATCA was 40.7 and 13.9 min in rabbits and swine, respectively, while it could not be determined in rats with confidence. The current study suggests that cyanide exposure may be verified shortly after exposure by determining significantly elevated cyanide and SCN− in each animal model and ATCA may be used when the ATCA detoxification pathway is significant. PMID:24711295

Cyanide toxicokinetics: the behavior of cyanide, thiocyanate and 2-amino-2-thiazoline-4-carboxylic acid in multiple animal models.

PubMed

Bhandari, Raj K; Oda, Robert P; Petrikovics, Ilona; Thompson, David E; Brenner, Matthew; Mahon, Sari B; Bebarta, Vikhyat S; Rockwood, Gary A; Logue, Brian A

2014-05-01

Cyanide causes toxic effects by inhibiting cytochrome c oxidase, resulting in cellular hypoxia and cytotoxic anoxia, and can eventually lead to death. Cyanide exposure can be verified by direct analysis of cyanide concentrations or analyzing its metabolites, including thiocyanate (SCN(-)) and 2-amino-2-thiazoline-4-carboxylic acid (ATCA) in blood. To determine the behavior of these markers following cyanide exposure, a toxicokinetics study was performed in three animal models: (i) rats (250-300 g), (ii) rabbits (3.5-4.2 kg) and (iii) swine (47-54 kg). Cyanide reached a maximum in blood and declined rapidly in each animal model as it was absorbed, distributed, metabolized and eliminated. Thiocyanate concentrations rose more slowly as cyanide was enzymatically converted to SCN(-). Concentrations of ATCA did not rise significantly above the baseline in the rat model, but rose quickly in rabbits (up to a 40-fold increase) and swine (up to a 3-fold increase) and then fell rapidly, generally following the relative behavior of cyanide. Rats were administered cyanide subcutaneously and the apparent half-life (t1/2) was determined to be 1,510 min. Rabbits were administered cyanide intravenously and the t1/2 was determined to be 177 min. Swine were administered cyanide intravenously and the t1/2 was determined to be 26.9 min. The SCN(-) t1/2 in rats was 3,010 min, but was not calculated in rabbits and swine because SCN(-) concentrations did not reach a maximum. The t1/2 of ATCA was 40.7 and 13.9 min in rabbits and swine, respectively, while it could not be determined in rats with confidence. The current study suggests that cyanide exposure may be verified shortly after exposure by determining significantly elevated cyanide and SCN(-) in each animal model and ATCA may be used when the ATCA detoxification pathway is significant.

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

PubMed

Musah, Sadiatu; Schlueter, Connie F; Humphrey, David M; Powell, Karen S; Roberts, Andrew M; Hoyle, Gary W

2017-01-15

Chlorine is a pulmonary toxicant to which humans can be exposed through accidents or intentional releases. Acute effects of chlorine inhalation in humans and animal models have been well characterized, but less is known about persistent effects of acute, high-level chlorine exposures. In particular, animal models that reproduce the long-term effects suggested to occur in humans are lacking. Here, we report the development of a rabbit model in which both acute and persistent effects of chlorine inhalation can be assessed. Male New Zealand White rabbits were exposed to chlorine while the lungs were mechanically ventilated. After chlorine exposure, the rabbits were extubated and were allowed to survive for up to 24h after exposure to 800ppm chlorine for 4min to study acute effects or up to 7days after exposure to 400ppm for 8min to study longer term effects. Acute effects observed 6 or 24h after inhalation of 800ppm chlorine for 4min included hypoxemia, pulmonary edema, airway epithelial injury, inflammation, altered baseline lung mechanics, and airway hyperreactivity to inhaled methacholine. Seven days after recovery from inhalation of 400ppm chlorine for 8min, rabbits exhibited mild hypoxemia, increased area of pressure-volume loops, and airway hyperreactivity. Lung histology 7days after chlorine exposure revealed abnormalities in the small airways, including inflammation and sporadic bronchiolitis obliterans lesions. Immunostaining showed a paucity of club and ciliated cells in the epithelium at these sites. These results suggest that small airway disease may be an important component of persistent respiratory abnormalities that occur following acute chlorine exposure. This non-rodent chlorine exposure model should prove useful for studying persistent effects of acute chlorine exposure and for assessing efficacy of countermeasures for chlorine-induced lung injury. Copyright © 2016 Elsevier Inc. All rights reserved.

Exploration of the wound healing effect of topical administration of nicotine in combination with collagen scaffold in a rabbit model.

PubMed

Masuoka, Hiromu; Morimoto, Naoki; Sakamoto, Michiharu; Ogino, Shuichi; Suzuki, Shigehiko

2016-06-01

Nicotine has been reported to prolong the wound healing; however, we showed that the topical application of 10(-4) M nicotine promoted murine wound healing. The objective of this study was to explore the wound healing effects of nicotine in combination with collagen scaffold using skin defects in rabbit. Three full-thickness skin defects 8 mm in diameter were made on the rabbit auricle. Artificial dermis was applied to the defects, and 10 μl of nicotine solution (10(-5), 10(-4), and10(-3) M), bFGF solution (0.5 μg/10 μl), and both bFGF and 10(-4) M nicotine solutions were injected into the artificial dermis once daily for 7 days. Rabbits were sacrificed on day 10, 15, or 20, and the wound healing process was evaluated. bFGF was superior in the formation of the dermis-like tissue and capillaries. In nicotine groups, the epithelial length and the dermis-like tissue formations in the 10(-4) M group were superior, in contrast, those were inhibited in the 10(-3) M group. The synergistic effect of bFGF and 10(-4) M nicotine was not confirmed. This study suggests that the topical application of 10(-4) M nicotine promoted wound healing in rabbit, but the effect was not apparent compared with murine models.

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.

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.

Hypercholesterolemia increases plasma saturated and n-6 fatty acids altering prostaglandin homeostasis and promotes endothelial dysfunction in rabbits.

PubMed

Medina, M; Alberto, M R; Sierra, L; Van Nieuwenhove, C; Saad, S; Isla, M I; Jerez, S

2014-07-01

The present study evaluated the plasma fatty acid levels and the vascular prostaglandin (PG) release in a rabbit model of early hypercholesterolemia with endothelial dysfunction. Rabbits were fed either a control diet (CD) or a diet containing 1 % cholesterol (HD) for 5-6 weeks. The level of fatty acids was measured in plasma. The levels of PG and nitric oxide (NO) released from the aorta were also determined. Vascular morphology of the aorta was characterized by intima and media thickness measurements. The rabbits fed with HD had higher levels of arachidonic acid (ARA) and lower levels of oleic acid. The linoleic acid level was unchanged. PGI(2) and NO were diminished and PGF(2α) levels, the PGI(2)/TXA(2) ratio and the intima/media ratio were increased in rabbits fed with HD. In conclusion, feeding HD for a short period increased ARA plasma levels and unbalanced release of vasodilator/vasoconstrictor PG redirected the pathway to vasoconstrictor metabolite release. These lipid metabolism alterations in addition to the reduced NO levels and the moderate changes in the vascular morphology contributed to the endothelial dysfunction in this animal model. Therefore, the present findings support the importance of early correction or prevention of high cholesterol levels to disrupt the endothelial dysfunction process that leads to cardiovascular disease.

Evolution of the paranasal sinuses' anatomy through the ages

PubMed Central

Mavrodi, Alexandra

2013-01-01

Previously, anatomists considered paranasal sinuses as a mysterious region of the human skull. Historically, paranasal sinuses were first identified by ancient Egyptians and later, by Greek physicians. After a long period of no remarkable improvement in the understanding of anatomy during the Middle Ages, anatomists of the Renaissance period-Leonardo da Vinci and Vesalius-made their own contribution. Nathaniel Highmore's name is also associated with the anatomy of paranasal sinuses as he was first to describe the maxillary sinus. PMID:24386595

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 implicated in circadian rhythm and arousal, as well as in motricity. © 2018 Anatomical Society.

Models of torsades de pointes: effects of FPL64176, DPI201106, dofetilide, and chromanol 293B in isolated rabbit and guinea pig hearts.

PubMed

Cheng, Hsien C; Incardona, Josephine

2009-01-01

For studying the torsades de pointes (TdP) liability of a compound, most high and medium throughput methods use surrogate markers such as HERG inhibition and QT prolongation. In this study, we have tested whether isolated hearts may be modified to allow TdP to be the direct readout. Isolated spontaneously beating rabbit and guinea pig hearts were perfused according to the Langendorff method in hypokalemic (2.1 mM) solution. The in vitro lead II ECG equivalent and the incidence of TdP were monitored for 1 h. In addition, heart rate, QTc, Tp-Te, short-term variability (STV), time to arrhythmia, and time to TdP were also analyzed. FPL64176, a calcium channel activator; and DPI201106, a sodium channel inactivation inhibitor, produced TdP in isolated rabbit and guinea pig hearts in a concentration dependent manner; guinea pig hearts were 3- to 5-fold more sensitive than rabbit hearts. Both compounds also increased QTc and STV. In contrast, dofetilide, an IKr inhibitor, produced no (or a low incidence of) TdP in both species, in spite of prolongation of QTc intervals. Chromanol 293B, an IKs inhibitor, did not produce TdP in rabbit hearts but elicited TdP concentration dependently in guinea pig hearts even though the compound had no effect on QTc intervals. IKs inhibition appears to be more likely to produce TdP in isolated guinea pig hearts than IKr inhibition. Chromanol 293B did not produce TdP in rabbit hearts presumably due to a low level of IKs channels in the heart. TdP produced in this study was consistent with the notion that its production was a consequence of reduced repolarization reserve, thereby causing rhythmic abnormalities. This isolated, perfused, and spontaneously beating rabbit and guinea pig heart preparation in hypokalemic medium may be useful as a preclinical test model for studying proarrhythmic liability of compounds in new drug development.

Successful Microbubble Sonothrombolysis without Tissue Plasminogen Activator in a Rabbit Model of Acute Ischemic Stroke

PubMed Central

Culp, William C.; Flores, Rene; Brown, Aliza T.; Lowery, John D.; Roberson, Paula K.; Hennings, Leah J.; Woods, Sean D.; Hatton, Jeff H.; Culp, Benjamin C.; Skinner, Robert D.; Borrelli, Michael J.

2011-01-01

Background Microbubbles (MB) combined with ultrasound (US) have been shown to lyse clots without tissue plasminogen activator (tPA) both in vitro and in vivo. We evaluated sonothrombolysis with three types of MB using a rabbit embolic stroke model. Methods New Zealand White rabbits (n=74) received internal carotid angiographic embolization of single 3 day-old cylindrical clots (0.6×4.0-mm). Groups included: 1) control (n=11) embolized without treatment, 2) tPA (n=20), 3) tPA+US (n=10), 4) Perflutren Lipid MB+US (n=16), 5) albumin 3µm MB+US (n=8), and 6) tagged albumin 3µm MB+US (n=9). Treatment began 1 hour post-embolization. Ultrasound was pulsed-wave (1 MHz; 0.8 W/cm2) for 1 hour; rabbits with tPA received intravenous tPA (0.9 mg/kg) over 1 hour. Lipid MB dose was intravenous (0.16 mg/kg) over 30 minutes. Dosage of 3µm MB was 5×109 MB intravenously alone or tagged with eptifibatide and fibrin antibody over 30 minutes. Rabbits were euthanized at 24 hours. Infarct volume was determined using vital stains on brain sections. Hemorrhage was evaluated on H&E sections. Results Infarct volume percent was lower for rabbits treated with Lipid MB+US (1.0%±0.6%; P=0.013), 3µm MB+US (0.7%±0.9%; P=0.018), and tagged 3µm MB+US (0.8%±0.8%; P=0.019) compared with controls (3.5%±0.8%). The three MB types collectively had lower infarct volumes (P=0.0043) than controls. Infarct volume averaged 2.2%±0.6% and 1.7%±0.8% for rabbits treated with tPA alone and tPA+US, respectively (P=NS). Conclusions Sonothrombolysis without tPA using these MB is effective in decreasing infarct volumes. Study of human application and further MB technique development are justified. PMID:21700942

Visualization of stereoscopic anatomic models of the paranasal sinuses and cervical vertebrae from the surgical and procedural perspective.

PubMed

Chen, Jian; Smith, Andrew D; Khan, Majid A; Sinning, Allan R; Conway, Marianne L; Cui, Dongmei

2017-11-01

Recent improvements in three-dimensional (3D) virtual modeling software allows anatomists to generate high-resolution, visually appealing, colored, anatomical 3D models from computed tomography (CT) images. In this study, high-resolution CT images of a cadaver were used to develop clinically relevant anatomic models including facial skull, nasal cavity, septum, turbinates, paranasal sinuses, optic nerve, pituitary gland, carotid artery, cervical vertebrae, atlanto-axial joint, cervical spinal cord, cervical nerve root, and vertebral artery that can be used to teach clinical trainees (students, residents, and fellows) approaches for trans-sphenoidal pituitary surgery and cervical spine injection procedure. Volume, surface rendering and a new rendering technique, semi-auto-combined, were applied in the study. These models enable visualization, manipulation, and interaction on a computer and can be presented in a stereoscopic 3D virtual environment, which makes users feel as if they are inside the model. Anat Sci Educ 10: 598-606. © 2017 American Association of Anatomists. © 2017 American Association of Anatomists.

Study of relationship of concha bullosa to nasal septal deviation and sinusitis.

PubMed

Bhandary, Satheesh Kumar; Kamath P, Shrinath D

2009-09-01

To study the etiological role of concha bollosa in deviated nasal septum (DNS) and sinusitis. In this retrospective study 419 consecutive CT scans of paranasal sinuses done between October 2005 and September 2007 were serially evaluated for the presence of concha, DNS and sinusitis. Out of 419 CT scans evaluated, concha bullosa was present in 40.3% of patients. Among these, concha co-existent DNS was found in 87.5%, air column between DNS and concha was found in 88.5% and sinus disease was present in 69.2% of patients. Presence of air column between DNS and concha excludes the etiological role of concha in DNS. Concha bullosa may predispose to sinusitis.

Echocardiographic imaging techniques with subcostal and right parasternal longitudinal views in detecting sinus venosus atrial septal defects.

PubMed

McDonald, R W; Rice, M J; Reller, M D; Marcella, C P; Sahn, D J

1996-01-01

Sinus venosus atrial septal defects are frequently missed and difficult to visualize with conventional two-dimensional echocardiographic views. Using modified subcostal and right parasternal longitudinal views, nine patients were found to have a sinus venosus atrial septal defect. The modified subcostal view showed a sinus venosus atrial septal defect in all nine patients; three patients had secundum atrial septal defects as well. The right parasternal view detected only six patients with sinus venosus atrial septal defect. Partial anomalous pulmonary venous return was diagnosed in seven patients using these views. The combination of subcostal and right parasternal longitudinal imaging views will improve the detection of sinus venosus atrial septal defects.

Multislice CT imaging of ruptured left sinus of Valsalva aneurysm with fistulous track between left sinus and right atrium.

PubMed

Pampapati, Praveenkumar; Rao, Hejmadi Tati Gururaj; Radhesh, Srinivasan; Anand, Hejjaji Krishnamurthy; Praveen, Lokkur Srinivasamurthy

2011-01-01

Sinus of valsalva aneurysm is a rare condition arising from any of the three aortic sinuses. Among them, an aneurysm arising from the left coronary sinus is the rarest. Most of these cases were earlier diagnosed using echocardiography and conventional angiography. But with the availability of advanced imaging modalities like 64 slice cardiac CT and MR modalities, this condition can be accurately assessed noninvasively. We report a case of ruptured aneurysm originating from the left coronary sinus with a long windsock type of fistulous track between the aneurysm and right atrium evaluated by 64 slice cardiac CT imaging. This was later confirmed perioperatively.

Current Status of the Application of Intracranial Venous Sinus Stenting

PubMed Central

Xu, Kan; Yu, Tiecheng; Yuan, Yongjie; Yu, Jinlu

2015-01-01

The intracranial venous sinus is an important component of vascular disease. Many diseases involve the venous sinus and are accompanied by venous sinus stenosis (VSS), which leads to increased venous pressure and high intracranial pressure. Recent research has focused on stenting as a treatment for VSS related to these diseases. However, a systematic understanding of venous sinus stenting (VS-Stenting) is lacking. Herein, the literature on idiopathic intracranial hypertension (IIH), venous pulsatile tinnitus, sinus thrombosis, high draining venous pressure in dural arteriovenous fistula (AVF) and arteriovenous malformation (AVM), and tumor-caused VSS was reviewed and analyzed to summarize experiences with VS-Stenting as a treatment. The literature review showed that satisfactory therapeutic effects can be achieved through stent angioplasty. Thus, the present study suggests that selective stent release in the venous sinus can effectively treat these diseases and provide new possibilities for treating intracranial vascular disease. PMID:26516306

Comprehensive review on endonasal endoscopic sinus surgery

PubMed Central

Weber, Rainer K.; Hosemann, Werner

2015-01-01

Endonasal endoscopic sinus surgery is the standard procedure for surgery of most paranasal sinus diseases. Appropriate frame conditions provided, the respective procedures are safe and successful. These prerequisites encompass appropriate technical equipment, anatomical oriented surgical technique, proper patient selection, and individually adapted extent of surgery. The range of endonasal sinus operations has dramatically increased during the last 20 years and reaches from partial uncinectomy to pansinus surgery with extended surgery of the frontal (Draf type III), maxillary (grade 3–4, medial maxillectomy, prelacrimal approach) and sphenoid sinus. In addition there are operations outside and beyond the paranasal sinuses. The development of surgical technique is still constantly evolving. This article gives a comprehensive review on the most recent state of the art in endoscopic sinus surgery according to the literature with the following aspects: principles and fundamentals, surgical techniques, indications, outcome, postoperative care, nasal packing and stents, technical equipment. PMID:26770282

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

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

Musah, Sadiatu; Schlueter, Connie F.; Humphrey, Da

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

KATP channel inhibition blunts electromechanical decline during hypoxia in left ventricular working rabbit hearts

PubMed Central

Garrott, Kara; Kuzmiak‐Glancy, Sarah; Wengrowski, Anastasia; Zhang, Hanyu; Rogers, Jack

2017-01-01

Key points Heart function is critically dependent upon the balance of energy production and utilization. Sarcolemmal ATP‐sensitive potassium channels (KATP channels) in cardiac myocytes adjust contractile function to compensate for the level of available energy.Understanding the activation of KATP channels in working myocardium during high‐stress situations is crucial to the treatment of cardiovascular disease, especially ischaemic heart disease.Using a new optical mapping approach, we measured action potentials from the surface of excised contracting rabbit hearts to assess when sarcolemmal KATP channels were activated during physiologically relevant workloads and during gradual reductions in myocardial oxygenation.We demonstrate that left ventricular pressure is closely linked to KATP channel activation and that KATP channel inhibition with a low concentration of tolbutamide prevents electromechanical decline when oxygen availability is reduced. As a result, KATP channel inhibition probably exacerbates a mismatch between energy demand and energy production when myocardial oxygenation is low. Abstract Sarcolemmal ATP‐sensitive potassium channel (KATP channel) activation in isolated cells is generally understood, although the relationship between myocardial oxygenation and KATP activation in excised working rabbit hearts remains unknown. We optically mapped action potentials (APs) in excised rabbit hearts to test the hypothesis that hypoxic changes would be more severe in left ventricular (LV) working hearts (LWHs) than Langendorff (LANG) perfused hearts. We further hypothesized that KATP inhibition would prevent those changes. Optical APs were mapped when measuring LV developed pressure (LVDP), coronary flow rate and oxygen consumption in LANG and LWHs. Hearts were paced to increase workload and perfusate was deoxygenated to study the effects of myocardial hypoxia. A subset of hearts was perfused with 1 μm tolbutamide (TOLB) to identify the level of AP duration (APD) shortening attributed to KATP channel activation. During sinus rhythm, APD was shorter in LWHs compared to LANG hearts. APD in both LWHs and LANG hearts dropped steadily during deoxygenation. With TOLB, APDs in LWHs were longer at all workloads and APD reductions during deoxygenation were blunted in both LWHs and LANG hearts. At 50% perfusate oxygenation, APD and LVDP were significantly higher in LWHs perfused with TOLB (199 ± 16 ms; 92 ± 5.3 mmHg) than in LWHs without TOLB (109 ± 14 ms, P = 0.005; 65 ± 6.5 mmHg, P = 0.01). Our results indicate that KATP channels are activated to a greater extent in perfused hearts when the LV performs pressure–volume work. The results of the present study demonstrate the critical role of KATP channels in modulating myocardial function over a wide range of physiological conditions. PMID:28177123

Finite element analysis of the biomechanical interaction between coronary sinus and proximal anchoring stent in coronary sinus annuloplasty

PubMed Central

Pham, Thuy; Deherrera, Milton; Sun, Wei

2013-01-01

Recent clinical studies of the percutaneous transvenous mitral annuloplasty (PTMA) devices have shown a short-term reduction of mitral regurgitation (MR) after implantation. However, adverse events associated with the devices such as compression and perforation of vessel branches, device migration and fracture were reported. In this study, a finite element analysis was performed to investigate the biomechanical interaction between the proximal anchor stent of a PTMA device and the coronary sinus (CS) vessel in three steps including i) the stent release and contact with the CS wall, ii) the axial pull at the stent connector and iii) the pressure inflation of the vessel wall. To investigate the impact of the material properties of tissues and stents on the interactive responses, the CS vessel was modeled with human and porcine material properties, and the proximal stent was modeled with two different Nitinol materials with one being stiffer than the other. The results indicated that the vessel wall stresses and contact forces imposed by the stents were much higher in human than porcine models. However, the mechanical differences induced by the two stent types were relatively small. The softer stent exhibited a better fatigue safety factor when deployed in the human model than in the porcine model. These results underscored the importance of the CS tissue mechanical properties. Higher vessel wall stress and stent radial force were obtained in human model than those in porcine model, which also brought up questions as to the validity of using porcine model to assess device mechanical function. The quantification of these biomechanical interactions can offer scientific insight into the development and optimization of PTMA device design. PMID:23405942

Lectin histochemistry of the rat lymph node: visualisation of stroma, blood vessels, sinuses, and macrophages. A contribution to the concept of an immune accessory role of sinus-lining endothelia.

PubMed

Düllmann, Jochen; Van Damme, Els J M; Peumans, Willy J; Ziesenitz, Maike; Schumacher, Udo

2002-01-01

The lectin Chelidonium majus agglutinin (CMA) was previously shown to visualise endothelia of all blood vessels and those lining sinuses of red pulp, stromal reticular meshwok (RM) and dendritic cells of lymphatic follicles in white pulp of the spleen in rats. The aim of the present study was the analysis of CMA and some other lectins in labelling RM, vascular structures and macrophages in lymph nodes of rats. It appeared that CMA stained the entire RM, dendritic cells, lining cells of sinuses and all types of blood vessels. Sinus-lining cells of lymph nodes were labelled with CMA and mannose-, GalNac-, and sialic acid-specific lectins. Moreover, lymph node macrophages were labelled above all by mannose specific lectins. The broad lectin-binding pattern of sinuses--not observed in rat spleen- and CMA-reactivity of both sinus-lining and dendritic cells corroborates the hypothesis that lymph node sinus-lining endothelia are precursors or a special type of immune accessory cells.

Benefit from the minimally invasive sinus technique.

PubMed

Salama, N; Oakley, R J; Skilbeck, C J; Choudhury, N; Jacob, A

2009-02-01

Sinus drainage is impeded by the transition spaces that the anterior paranasal sinuses drain into, not the ostia themselves. Addressing the transition spaces and leaving the ostia intact, using the minimally invasive sinus technique, should reverse chronic rhinosinusitis. To assess patient benefit following use of the minimally invasive sinus technique for chronic rhinosinusitis. One hundred and forty-three consecutive patients underwent the minimally invasive sinus technique for chronic rhinosinusitis. Symptoms (i.e. blocked nose, poor sense of smell, rhinorrhoea, post-nasal drip, facial pain and sneezing) were recorded using a visual analogue scale, pre-operatively and at six and 12 weeks post-operatively. Patients were also surveyed using the Glasgow benefit inventory, one and three years post-operatively. We found a significant reduction in all nasal symptom scores at six and 12 weeks post-operatively, and increased total quality of life scores at one and three years post-operatively (25.2 and 14.8, respectively). The patient benefits of treatment with the minimally invasive sinus technique compare with the published patient benefits for functional endoscopic sinus surgery.

Pre- and postoperative assessment of sinus grafting procedures using cone-beam computed tomography compared with panoramic radiographs.

PubMed

Baciut, Mihaela; Hedesiu, Mihaela; Bran, Simion; Jacobs, Reinhilde; Nackaerts, Olivia; Baciut, Grigore

2013-05-01

The present study evaluated the clinical validity of cone-beam computed tomography (CBCT) scans in comparison to panoramic radiographs regarding preoperative implant planning in combination with sinus grafting procedures. Preoperative assessment of the maxillary sinuses and implant planning using panoramic radiographs and CBCT scans was performed on 16 sinuses (13 patients) and comprised choice of treatment, timing of implant placement, sinus morphology, level of confidence, complication prediction and graft volume assessment. Six examiners were involved in the study. In the majority of cases there was a concordance between the treatment type based on either panoramic radiographs or CBCT. If any difference was found, this was due to an overestimation of bone quantity and quality on panoramic radiographs. The assessment of sinus morphology showed a significantly higher detection rate of sinus mucosal hypertrophy on CBCT. The most appealing result is a significant increase in surgical confidence and a significantly better prediction of complications when using CBCT. A preoperative planning based on CBCT seems to improve sinus diagnostics and surgical confidence. © 2012 John Wiley & Sons A/S.

Assessment of gastrointestinal pH, fluid and lymphoid tissue in the guinea pig, rabbit and pig, and implications for their use in drug development.

PubMed

Merchant, Hamid A; McConnell, Emma L; Liu, Fang; Ramaswamy, Chandrasekaran; Kulkarni, Rucha P; Basit, Abdul W; Murdan, Sudaxshina

2011-01-18

Laboratory animals are often used in drug delivery and research. However, basic information about their gastrointestinal pH, fluid volume, and lymphoid tissue is not completely known. We have investigated these post-mortem in healthy guinea pigs, rabbits and pigs, to assess their suitability for pre-clinical studies by comparing the results with reported human literature. The mean gastric pH (fed ad libitum) was 2.9 and 4.4 in guinea pig and pig, respectively. In contrast, a very low pH (1.6) was recorded in the rabbits. The small intestinal pH was found in the range of 6.4-7.4 in the guinea pigs and rabbits, whereas lower pH (6.1-6.7) was recorded in the pig, which may have consequences for ionisable or pH responsive systems when tested in pig. A relatively lower pH than in the small intestine was found in the caecum (6.0-6.4) and colon (6.1-6.6) of the guinea pig, rabbit and the pig. The water content in the gastrointestinal tract of guinea pig, rabbit and pig was 51g, 153g and 1546g, respectively. When normalized to the body weight, the guinea pig, had larger amounts of water compared to the rabbit and the pig (guinea pig>rabbit>pig); in contrast, a reverse order was found when normalized to per unit length of the gut (guinea pig

Frontal sinus depth at four landmarks in breeds of dog typically affected by sinonasal aspergillosis.

PubMed

Burrow, R; McCarroll, D; Baker, M; Darby, P; McConnell, F; Cripps, P

2012-01-07

The objective of this study was to assess whether the frontal sinuses in dogs with aspergillosis and of breeds typically affected by this condition were deeper at a more caudal location. CT scans of the head performed at the Small Animal Teaching Hospital, University of Liverpool, between April 2007 and March 2009 for dogs diagnosed with aspergillosis (group 1) and unaffected dogs of similar breeds (group 2) were selected for study. Sinus depth was measured at four standardised locations from reconstructed images of these CT scans. Data were compared for differences in sinus depth between groups and between landmarks. No significant difference was found between measurements within individual dogs or for each of the various landmarks between groups. Difference in depth of the sinuses between landmarks was significant (P<0.001). Sinus depth was significantly greater at the more caudal landmarks and was shallowest at the previously recommended landmark for sinus entry. In 54 per cent of dogs, the frontal sinus depth measured less than or equal to 2 cm at one or more of the landmarks. Sinus entry at the deepest point will reduce the risk of accidentally damaging underlying structures. This may be approximately 1 cm caudal, in breeds of dog that typically develop aspergillosis, to a previously suggested landmark.

Paranasal sinus mucoceles: our clinical experiments

PubMed Central

Topdag, Murat; Iseri, Mete; Sari, Fatih; Erdogan, Selvet; Keskin, I Gurkan

2015-01-01

Objectives: We present the clinical and radiological features, treatment protocols, and medium-long-term results of our patients following surgery for paranasal sinus mucocele, along with a review of the relevant literature. Materials and methods: A total of 18 patients (11 women and 7 men) who underwent surgery for paranasal sinus mucocele at Kocaeli University Faculty of Medicine, Department of Otolaryngology, between 2006 and 2013 were examined retrospectively. The mean patient age was 41 (range 4-73). Demographic and radiological features, symptoms, treatment protocols, and postoperative outcomes were recorded. Results: The most frequently affected sinus was the maxillary sinus (n=9, 50%) followed by the frontal sinus (n=6, 33%) and sphenoidal sinus (n=3, 16%). The main symptom was headache. Endoscopic marsupialization of the mucocele was applied in all 18 patients, while frontal sinus exploration with the osteoplastic flap procedure was performed in one patient and the Caldwell-Luc operation was performed in another patient. The Caldwell-Luc procedure was subsequently required in one patient (6%) and endoscopic revision surgery was required in another patient (6%). Conclusion: Sinus mucocele that enlarges, eroding the surrounding bone tissue, and induces various clinical symptoms due to the impression of the expansile mass, is treated surgically, and must be planned carefully to prevent serious complications. PMID:26770462

Chronic Rhinosinusitis: Potential Role of Microbial Dysbiosis and Recommendations for Sampling Sites

PubMed Central

Copeland, Elizabeth; Leonard, Katherine; Carney, Richard; Kong, Justin; Forer, Martin; Naidoo, Yuresh; Oliver, Brian G. G.; Seymour, Justin R.; Woodcock, Stephen; Burke, Catherine M.; Stow, Nicholas W.

2018-01-01

Chronic rhinosinusitis (CRS) is an inflammatory condition that affects up to 12% of the human population in developed countries. Previous studies examining the potential role of the sinus bacterial microbiota within CRS infections have found inconsistent results, possibly because of inconsistencies in sampling strategies. The aim of this study was to determine whether the sinus microbiome is altered in CRS and additionally if the middle meatus is a suitable representative site for sampling the sinus microbiome. Swab samples were collected from 12 healthy controls and 21 CRS patients, including all eight sinuses for CRS patients and between one and five sinuses for control subjects. The left and right middle meatus and nostril swabs were also collected. Significant differences in the sinus microbiomes between CRS and control samples were revealed using high-throughput 16S rRNA gene sequencing. The genus Escherichia was over-represented in CRS sinuses, and associations between control patients and Corynebacterium and Dolosigranulum were also identified. Comparisons of the middle meatuses between groups did not reflect these differences, and the abundance of the genus Escherichia was significantly lower at this location. Additionally, intra-patient variation was lower between sinuses than between sinus and middle meatus, which together with the above results suggests that the middle meatus is not an effective representative sampling site. PMID:29541629

Drainage of the maxillary sinus: a comparative anatomy study in humans and goats.

PubMed

Ford, Rebecca L; Barsam, Alon; Velusami, Prabhu; Ellis, Harold

2011-02-01

The maxillary sinuses are the most frequently infected paranasal sinuses in humans. It has been suggested that infection occurs relatively commonly in the maxillary sinuses owing to the position of their ostia high on their superomedial walls, which may be suboptimal for natural drainage. This may represent evolutionary lag, whereby the ostia remained in a quadrupedal position as bipedal humans evolved from their primate ancestors. This study examined the hypothesis that drainage of the maxillary sinus is optimal in the quadrupedal position. The drainage of the human maxillary sinus and an analogous quadruped, the goat, was examined and compared in the upright, quadrupedal, and intermediate positions. Department of Anatomy, King's College London. Cadaveric human and goat maxillary sinuses were filled with saline in each position and the volume at which saline overflowed through the ostia was noted. Volume at which spontaneous drainage occurred through ostia. The volume of saline instilled before drainage was maximal in the upright position and reduced with each increase in anterior tilt, with drainage occurring most easily at 90° for both human and goat sinuses. Drainage was significantly better in the quadrupedal head position than upright in both species (p < .01). This study demonstrated that human maxillary sinuses exhibit better passive drainage through their ostia when tilted anteriorly to mimic a quadrupedal head position. This may be an example of an evolutionary lag phenomenon and could be one etiologic factor in the prevalence of maxillary sinusitis in humans.

Microbiology of intracranial abscesses associated with sinusitis of odontogenic origin.

PubMed

Brook, Itzhak

2006-12-01

The unique microbiology of sinusitis of dental origin that is associated with intracranial abscesses (IAs) and the correlation between the organisms at the two sites has not been reported before. This report describes the author's experience during a 30-year period in studying the microbiology of 8 IAs and their corresponding sinusitis of dental origin. Aspirates of pus from 8 infected sinuses associated with odontogenic infections and their corresponding IAs were studied for aerobic and anaerobic bacteria. Polymicrobial flora was found in all 8 sinuses and 7 IAs, and the number of isolates varied from 1 to 5. Anaerobic bacteria were isolated from all sinuses and IAs. A total of 28 isolates (3.5 isolates per site; 25 strict anaerobic, 1 aerobic or facultative, and 2 microaerophilic) were recovered from the sinuses, and 20 isolates (2.5 isolates per site; 16 strict anaerobic, 1 aerobic or facultative, and 3 microaerophilic) were found in the IAs. The bacterial isolates were Fusobacterium spp (14), Prevotella spp (11), Peptostreptococcus spp (13), microaerophilic streptococci (5), Veillonella parvula (3), and beta-hemolytic streptococci group F(2). Concordance in the microbiological findings between the sinus and the IA was found in all instances; however, certain organisms were only present at one site. These data illustrate the concordance in the organisms recovered from sinusitis of dental origin and their associated IAs and confirm the importance of anaerobic bacteria in sinusitis and IAs of dental origin.

Paranasal sinus pathogens in children with cystic fibrosis: do they relate to lower respiratory tract pathogens and is eradication successful?

PubMed

Wilson, P; Lambert, C; Carr, S B; Pao, C

2014-07-01

The study aims were to assess the association of microflora between the paranasal sinus and the lower airways of children attending a regional paediatric cystic fibrosis centre and to determine the performance of an eradication treatment protocol for positive paranasal sinus samples. Paired nasal lavage and lower airway samples (cough swabs or sputum) were taken from 54 children with cystic fibrosis (median age 11 years). Positive paranasal sinus samples received eradication treatment, using oral and sinonasal nebulised antibiotics. A correlation between paranasal sinus and lower airways was detected in 33/54 paired timed samples (p<0.02). Of 4/54 children who reported sinus symptoms, only 2 had paranasal sinus positive samples. 28 positive nasal lavage samples cultured 8 Pseudomonas aeruginosa (PA), 8 Staphylococcus aureus (SA) and 12 other bacterial pathogens. Eradication using sinonasal nebulised antibiotics and oral antibiotics showed a success of 14/21 (67%) treated paranasal sinus positive samples at 1 month & 3 months after treatment. Success rate was 75% in the PA group and 71% in the SA group. Ongoing monitoring with nasal lavage will continue. There was agreement between pathogens or lack of them found in the paranasal sinus and lower airways. Paranasal infection is often asymptomatic in children with cystic fibrosis. The eradication protocol for paranasal sinus pathogens had a good success rate. Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

Diagnosis of carotid sinus hypersensitivity in older adults: carotid sinus massage in the upright position is essential

PubMed Central

Parry, S; Richardson, D; O'Shea, D; Sen, B; Kenny, R

2000-01-01

OBJECTIVE—To assess the diagnostic value of supine and upright carotid sinus massage in elderly patients.
DESIGN—Prospective controlled cohort study.
SETTING—Three inner city accident and emergency departments and a dedicated syncope facility.
PATIENTS—1375 consecutive patients aged > 55 years presenting with unexplained syncope and drop attacks; 25 healthy controls.
INTERVENTIONS—Bilateral supine carotid sinus massage, repeated in the 70° head up tilt position if the initial supine test was not diagnostic of cardioinhibitory and mixed carotid sinus hypersensitivity.
MAIN OUTCOME MEASURES—Diagnosis of cardioinhibitory or mixed carotid sinus hypersensitivity; clinical characteristics of supine v upright positive groups.
RESULTS—226 patients were excluded for contraindications to carotid sinus massage. Of 1149 patients undergoing massage, 223 (19%) had cardioinhibitory or mixed carotid sinus hypersensitivity; 70 (31%) of these had a positive response to massage with head up tilt following negative supine massage (95% confidence interval, 25.3% to 37.5%). None of the healthy controls showed carotid sinus hypersensitivity on erect or supine massage. The initially positive supine test had 74% specificity and 100% sensitivity; these were both 100% for the upright positive test. The clinical characteristics of the supine v upright positive subgroups were similar.
CONCLUSIONS—The diagnosis of carotid sinus hypersensitivity amenable to treatment by pacing may be missed in one third of cases if only supine massage is performed. Massage should be done routinely in the head up tilt position if the initial supine test is negative.


Keywords: carotid sinus; tilt table testing; syncope; elderly patients PMID:10618329

Silent sinus syndrome an acquired condition and the essential role of otorhinolaryngologist consultation: a retrospective study.

PubMed

Martínez-Capoccioni, Gabriel; Varela-Martínez, Ernesto; Martín-Martín, Carlos

2016-10-01

The silent sinus syndrome (SSS) is a rare clinical entity characterized by painless spontaneous enophthalmos, hypoglobus, and facial deformities secondary to chronic maxillary sinus atelectasis. The aim of this study was to present an SSS diagnostic feature and evaluate the relationship between nasal septum deviation and maxillary sinus volume. A retrospective chart review of the clinical characteristics of 20 patients diagnosed with SSS between January 2013 and July 2014 were analyzed by the Department of Otorhinolaryngology of University Hospital Complex of Santiago de Compostela. 14 patients were females and six males. The mean age was 43 years (range 28-67 years). The right maxillary sinus was involved in 12 patients and the left maxillary sinus in eight patients. There was no statistical difference between gender and the presence of SSS. Maxillary sinus sizes were significantly smaller on the same side as the deviation (p < 0.01). 14 patients were treated with functional endoscopic sinus surgery (FESS) with maxillary antrostomy. We concluded that patients with SSS usually present with facial asymmetry, and the best approach to document and show all facial asymmetries for these patients are the frontal and craneo-caudal photographs. The present study demonstrates that, in adult patients, SSS generally presents a septal deviation to the affected maxillary sinus. We recommend performing a paranasal sinus CT scan when the patient has a deviated nasal septum, retraction of the malar eminence (evidenced from the viewpoint cranio-caudal facial) and hypoglobus. FESS performing postero-anterior uncinectomy and enlargement of the maxillary ostium is recommended to restore sinus pressure and prevent progression of the enophthalmos, hypoglobus and facial deformities.

Transverse sinus stenosis in adult patients with Chiari malformation type I.

PubMed

Saindane, Amit M; Bruce, Beau B; Desai, Nilesh K; Roller, Lauren A; Newman, Nancy J; Biousse, Valérie

2014-10-01

Transverse sinus stenosis is an imaging finding very highly associated with elevated intracranial pressure (ICP). Patients with the Chiari I malformation may potentially have elevated ICP due to impairment of CSF flow at the foramen magnum. This study evaluated whether patients with Chiari I malformation have transverse sinus stenosis and other imaging findings indicative of elevated ICP. Thirty patients with Chiari I malformation treated surgically and 76 control subjects were identified retrospectively. All control subjects and all patients with Chiari I malformation (preoperatively) underwent standardized contrast-enhanced brain MRI including a contrast-enhanced 3D T1-weighted sequence from which curved reformats of the transverse sinuses were generated. Two different readers blinded to the diagnosis then independently evaluated these curved reformats for severity of transverse sinus stenosis. Orbital and skull-base findings previously described in association with elevated ICP were also evaluated. Frequency of MRI findings between the two groups was compared. Patients with Chiari I malformation had significantly greater frequency of unilateral or bilateral transverse sinus stenosis than did control subjects (p < 0.001). There was complete interreader agreement on presence or absence of transverse sinus stenosis by patient (κ = 1.0 [95% CI, 0.89-1.0]). Logistic regression analysis controlling for age, sex, and body mass index found that transverse sinus stenosis significantly predicted Chiari I malformation versus control status (odds ratio, 11.2 [95% CI, 2.1-59.0]; p = 0.004) but that no other features were significantly associated with the Chiari I malformation. Patients with Chiari I malformation who had transverse sinus stenosis had significantly greater pituitary flattening than did those without transverse sinus stenosis (p = 0.02). Patients with Chiari I malformation have higher likelihood of transverse sinus stenosis, which may reflect associated elevated ICP.

Impact of paranasal sinus invasion on advanced nasopharyngeal carcinoma treated with intensity-modulated radiation therapy: the validity of advanced T stage of AJCC/UICC eighth edition staging system.

PubMed

Wang, Ying; Zhao, Jie; Zhao, Yajie; Yang, Zhen; Lei, Mingjun; Li, Zhanzhan; Wei, Rui; Chen, Dengming; He, Yuxiang; Shen, Liangfang

2018-05-01

The aim of this study was to clarify the prognostic role of paranasal sinus invasion in advanced NPC patients. Data of patients (n = 295) with advanced NPC (T3/T4N0-3 M0) treated with intensity-modulated radiation therapy were retrospectively analyzed. Staging was according to the AJCC/UICC eighth edition staging system. Overall survival (OS), local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS) were calculated, and differences were compared between patients with and without paranasal sinus invasion. Multivariate analysis was used to identify the independent predictors of different survival parameters. Paranasal sinus invasion was present in 126 of 295 (42.7%) patients. Sphenoid, ethmoid, maxillary, and frontal sinus involvements were present in 123 of 295 (41.7%), 95 of 295 (32.2%), 45 of 295 (15.3%), and 0 of 295 (0%), respectively. All survival parameters were significantly better in patients without paranasal sinus invasion. When paranasal sinus invasion was reclassified as T4 instead of T3, all survival rates, other than LRFS (P = 0.156), were significantly better in the new T3 patients, and differences in all survival parameters remained nonsignificant between T3 with paranasal sinus invasion and T4 without paranasal sinus invasion patients (all P > 0.05). In multivariate analysis, paranasal sinus invasion was found to be an independent negative prognostic factor for OS, DFS, and DMFS (P = 0.016, P = 0.004, and P = 0.006, respectively), but not for LRFS (P = 0.068). Paranasal sinus invasion has prognostic value in advanced NPC. It may be reasonable to classify paranasal sinus invasion as T4 stage. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Volumetric study in the development of paranasal sinuses by CT imaging in Asian: a pilot study.

PubMed

Park, Il-Ho; Song, Jong Seok; Choi, Hyuk; Kim, Tae Hoon; Hoon, Seung; Lee, Sang Hag; Lee, Heung-Man

2010-12-01

The volume of the air cavities in the paranasal sinuses is not only the simplest, but also the most important index for paranasal sinus evaluation. However, few volumetric studies have been performed in all age groups. The purpose of the current study was to outline the normal development of paranasal sinuses in all age groups, and to determine normal adult volumetric values by means of computed tomographic (CT) scan of paranasal sinus using volumetric procedures. A prospective volumetric CT study was conducted with 260 patients (520 sides) <25 years of age by means of three-dimensional reconstruction. The frontal sinuses began to pneumatize at 2 years of age, exhibited a faster growth pattern between 6 and 19 years of age, and the mean volume after full growth was 3.46±0.78 cm(3). The maxillary sinuses were pneumatized at birth in all cases, exhibited a monomodal growth pattern increasing until 15 years of age, and the mean volume after full growth was 14.83±1.36 cm(3). The floor of the sinus was the same level as the floor of the nasal cavity was between 7 and 15 years of age. The ethmoid sinuses exhibited a faster initial tendency to increase until 7 years of age, were completed by 15-16 years of age, and the mean volume after full growth was 4.51±0.92 cm(3). The sphenoid sinuses exhibited a growth spurt between 6 and 10 years of age, were completed by 15 years of age, and the mean volume after full growth was 3.47±0.93 cm(3). The results of this study are presented to provide the basis for an objective normal volume of sinus development and for studies involving diseases of the sinuses. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.