Collagen and mineral deposition in rabbit cortical bone during maturation and growth: effects on tissue properties.

PubMed

Isaksson, Hanna; Harjula, Terhi; Koistinen, Arto; Iivarinen, Jarkko; Seppänen, Kari; Arokoski, Jari P A; Brama, Pieter A; Jurvelin, Jukka S; Helminen, Heikki J

2010-12-01

We characterized the composition and mechanical properties of cortical bone during maturation and growth and in adult life in the rabbit. We hypothesized that the collagen network develops earlier than the mineralized matrix. Growth was monitored, and the rabbits were euthanized at birth (newborn), and at 1, 3, 6, 9, and 18 months of age. The collagen network was assessed biochemically (collagen content, enzymatic and non-enzymatic cross-links) in specimens from the mid-diaphysis of the tibia and femur and biomechanically (tensile testing) from decalcified whole tibia specimens. The mineralized matrix was analyzed using pQCT and 3-point bend tests from intact femur specimens. The collagen content and the Young's modulus of the collagen matrix increased significantly until the rabbits were 3 months old, and thereafter remained stable. The amount of HP and LP collagen cross-links increased continuously from newborn to 18 months of age, whereas PEN cross-links increased after 6 months of age. Bone mineral density and the Young's modulus of the mineralized bone increased until the rabbits were at least 6 months old. We concluded that substantial changes take place during the normal process of development in both the biochemical and biomechanical properties of rabbit cortical bone. In cortical bone, the collagen network reaches its mature composition and mechanical strength prior to the mineralized matrix. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Systemic levels of metallic ions released from orthodontic mini-implants.

PubMed

de Morais, Liliane Siqueira; Serra, Glaucio Guimarães; Albuquerque Palermo, Elisabete Fernandes; Andrade, Leonardo Rodrigues; Müller, Carlos Alberto; Meyers, Marc André; Elias, Carlos Nelson

2009-04-01

Orthodontic mini-implants are a potential source of metallic ions to the human body because of the corrosion of titanium (Ti) alloy in body fluids. The purpose of this study was to gauge the concentration of Ti, aluminum (Al), and vanadium (V), as a function of time, in the kidneys, livers, and lungs of rabbits that had Ti-6Al-4V alloy orthodontic mini-implants placed in their tibia. Twenty-three New Zealand rabbits were randomly divided into 4 groups: control, 1 week, 4 weeks, and 12 weeks. Four orthodontic mini-implants were placed in the left proximal tibia of 18 rabbits. Five control rabbits had no orthodontic mini-implants. After 1, 4, and 12 weeks, the rabbits were killed, and the selected tissues were extracted and prepared for analysis by graphite furnace atomic absorption spectrophotometry. Low amounts of Ti, Al, and V were detectable in the 1-week, 4-weeks, and 12-weeks groups, confirming that release of these metals from the mini-implants occurs, with diffusion and accumulation in remote organs. Despite the tendency of ion release when using the Ti alloy as orthodontic mini-implants, the amounts of metals detected were significantly below the average intake of these elements through food and drink and did not reach toxic concentrations.

Radiological, histological, and hematological evaluation of hydroxyapatite-coated resorbable magnesium alloy screws placed in rabbit tibia.

PubMed

Lim, Ho-Kyung; Byun, Soo-Hwan; Lee, Jin-Yong; Lee, Jung-Woo; Kim, Sae-Mi; Lee, Sung-Mi; Kim, Hyoun-Ee; Lee, Jong-Ho

2017-08-01

Titanium (Ti) screw has excellent mechanical property, and osseointegration capacity. However, they require surgery for removal. In contrast, polymer screws are resorbable, but they have poor mechanical properties. In this research, magnesium alloy screws (WE43: Mg-Y-Nd-Zr) that have advantages of titanium and polymer were manufactured. In addition, to increase biocompatibility and control degradation rate, the Mg alloy was coated with hydroxyapatite (HA). Torsion test and corrosion test were performed in vitro. For clinical, radiological and histological evaluation, on the eight rabbits, two HA-coated screws were installed in left tibia, and two noncoated screws were installed in right tibia. Each four rabbits were sacrificed 6 and 12 weeks postoperatively. For hematological evaluation, the same type of screws were installed on both legs. Complete blood count (CBC), Mg 2+ concentrate were sampled from the ear central artery on the operation day for a control point, and at 1, 2, 4, 6, 8, and 12 weeks. Mg alloy screws have no differences of biocompatibility according to the HA coating. However, resorption of screw was slower in case of the HA coating. The hematological problem related releasing of Mg was not found. The results suggest that Mg alloy screws have feasibility for clinical application. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1636-1644, 2017. © 2016 Wiley Periodicals, Inc.

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

PubMed

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

2009-01-01

This is the first work to report on additional Arginin-Glycin-Aspartat (RGD) coating on precoated hydroxyapatite (HA) surfaces regarding new bone formation, implant bone contact, and biocompatibility compared to pure HA coating and uncoated stainless K-wires. There were 39 rabbits in total with 6 animals for the RGD-HA and HA group for the 4 week time period and 9 animals for each of the 3 implant groups for the 12 week observation. A 2.0 K-wire either with RGD-HA or with pure HA coating or uncoated was placed into the intramedullary canal of the tibia. After 4 and 12 weeks, the tibiae were harvested and three different areas of the tibia were assessed for quantitative and qualitative histology for new bone formation, direct implant bone contact, and formation of multinucleated giant cells. Both RGD-HA and pure HA coating showed statistically higher new bone formation and implant bone contact after 12 weeks than the uncoated K-wire. There were no significant differences between the RGD-HA and the pure HA coating in new bone formation and direct implant bone contact after 4 and 12 weeks. The number of multinucleated giant did not differ significantly between the RGD-HA and HA group after both time points. Overall, no significant effects of an additional RGD coating on HA surfaces were detected in this model after 12 weeks. (c) 2008 Wiley Periodicals, Inc.

A light and scanning electron microscopic evaluation of electro-discharge-compacted porous titanium implants in rabbit tibia.

PubMed

Drummond, J F; Dominici, J T; Sammon, P J; Okazaki, K; Geissler, R; Lifland, M I; Anderson, S A; Renshaw, W

1995-01-01

This study used light and scanning electron microscopic (SEM) histomorphometric methods to quantitate the rate of osseointegration of totally porous titanium alloy (Ti-6Al-4V) implants prepared by a novel fabrication technique--electrodischarge compaction (EDC). EDC was used to fuse 150-250-micrometer spherical titanium alloy beads into 4 X 6 mm cylindrical implants through application of a 300-microsecond pulse of high-voltage/high-current density. Two sterilized implants were surgically placed into each tibia of 20 New Zealand white rabbits and left in situ for periods corresponding to 2, 4, 8, 12, and 24 weeks. At each time point, 4 rabbits were humanely killed, and the implants with surrounding bone were removed, fixed, and sectioned for light and SEM studies. The degree of osseointegration was quantitated by means of a True Grid Digitizing Pad and Jandel Scan Version 3.9 software on an IBM PS/2 computer. The total pore area occupied by bone was divided by the total pore area available for bone ingrowth, and a Bone Ingrowth Factor (BIF) was calculated as a percent. The light microscopic results showed BIFs of 4% at week 2, 47% at week 4, 62% at week 8, 84% at week 12, and greater than 90% at week 24. The SEM results showed BIFs of 5% at week 2, 34% at week 4, 69% at week 8, 75% at week 12, and in excess of 90% at week 24. The results of this study show that EDC implants are biocompatible and support rapid osseointegration in the rabbit tibia and suggest that, after additional studies, they may be suitable for use as dental implants in humans.

Evaluation of bone substitutes for treatment of peri-implant bone defects: biomechanical, histological, and immunohistochemical analyses in the rabbit tibia

PubMed Central

2016-01-01

Purpose We sought to evaluate the effectiveness of bone substitutes in circumferential peri-implant defects created in the rabbit tibia. Methods Thirty rabbits received 45 implants in their left and right tibia. A circumferential bone defect (6.1 mm in diameter/4 mm depth) was created in each rabbit tibia using a trephine bur. A dental implant (4.1 mm × 8.5 mm) was installed after the creation of the defect, providing a 2-mm gap. The bone defect gaps between the implant and the bone were randomly filled according to the following groups: blood clot (CO), particulate Bio-Oss® (BI), and Bio-Oss® Collagen (BC). Ten animals were euthanized after periods of 15, 30, and 60 days. Biomechanical analysis by means of the removal torque of the implants, as well as histologic and immunohistochemical analyses for protein expression of osteocalcin (OC), Runx2, OPG, RANKL, and TRAP were evaluated. Results For biomechanics, BC showed a better biological response (61.00±15.28 Ncm) than CO (31.60±14.38 Ncm) at 30 days. Immunohistochemical analysis showed significantly different OC expression in CO and BC at 15 days, and also between the CO and BI groups, and between the CO and BC groups at 60 days. After 15 days, Runx2 expression was significantly different in the BI group compared to the CO and BC groups. RANKL expression was significantly different in the BI and CO groups and between the BI and BC groups at 15 days, and also between the BI and CO groups at 60 days. OPG expression was significantly higher at 60 days postoperatively in the BI group than the CO group. Conclusions Collectively, our data indicate that, compared to CO and BI, BC offered better bone healing, which was characterized by greater RUNX2, OC, and OPG immunolabeling, and required greater reversal torque for implant removal. Indeed, along with BI, BC presents promising biomechanical and biological properties supporting its possible use in osteoconductive grafts for filling peri-implant gaps. PMID:27382506

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.

Physeal growth arrest by excessive compression: histological, biochemical, and micro-CT observations in rabbits.

PubMed

Yoo, Won Joon; Cheon, Jung-Eun; Lee, Hye Ran; Cho, Tae-Joon; Choi, In Ho

2011-12-01

Compressive force across the growth plate may cause retardation and even arrest of physeal growth. The purpose of this study was to investigate histologic changes, metabolic changes in terms of glycosaminoglycan (GAG) concentration, and contrast-enhanced micro-computed tomography (CEMCT) findings of physeal cartilage in a rabbit model of physeal damage caused by excessive compression. Compressive forces were applied via external fixators for two weeks to the growth plates of distal femurs and proximal tibiae of right hind-legs in 8-week-old rabbits. Left hind-legs remained intact and were used as controls. Forty-four bone specimens containing growth plates of distal femurs or proximal tibiae were harvested one week (n = 12) and four weeks (n = 32) after surgery, and examined for histologic findings (H&E staining) and GAGs quantification in physeal cartilage. After incubation in an ionic contrast material for 48 hours, specimens were scanned by CEMCT, and the pixel values of physeal cartilage were measured. CEMCT showed a thin, highly attenuated line parallel to the growth plate in compressed specimens harvested at four weeks after surgery, which was found to be transversely connected trabecular bone. In these specimens, GAG content in physeal cartilage was significantly lower, and CEMCT pixel values of physeal cartilage were significantly higher than in the specimens from the contralateral control side. Excessive compressive force applied to growth plates produces altered histologic features and metabolic function in terms of decreased GAG content in physeal cartilage, changes that can be demonstrated by CEMCT.

Bone Implant Interface Investigation by Synchrotron Radiation X-Ray Microfluorescence

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

Calasans-Maia, M.; Sales, E.; Lopes, R. T.

2010-04-06

Zinc is known to play a relevant role in growth and development; it has stimulatory effects on in vitro and in vivo bone formation and an inhibitory effect on in vitro osteoclastic bone resorption. The inorganic component of the bone tissue is nonstoichiometric apatite; changes in the composition of hidroxyapatite are subject of studies in order to improve the tissue response after implantation. The objective of this study was to investigate the effect of 0.5% zinc-containing hydroxyapatite in comparison to hydroxyapatite on osseous repair of rabbit's tibia. Cylinders (2x6 mm) of both materials were produced according to the specification ofmore » the International Organization for Standardization. Ethics Commission on Teaching and Research in Animals approved this project (HUAP-195/06). Fifteen White New Zealand rabbits were submitted to general anesthesia and two perforations (2 mm) were made in each tibia for implantation of zinc-containing hydroxyapatite cylinders (left tibia) and hydroxyapatite cylinders (right tibia). After 1, 2 and 4 weeks, the animals were killed and one fragment of each tibia with the cylinder was collected and embedded in a methacrylate-based resin and cut into slices (approx200 {mu}m thickness), parallel to the implant's long axis with a precision diamond saw for Synchrotron Radiation X-ray Microfluorescence investigation. The accomplishment of the standard procedures helped the planning, execution and the comparative analysis of the results. The chemical and physical properties of the biomaterials were modified after its implantation and the incorporation of zinc. Both materials are biocompatible and promote osteoconduction and favored bone repair.« less

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.

[Vancomycin-loaded bioactive borate glass for treatment of chronic osteomyelitis in rabbits].

PubMed

Xie, Zongping; Liu, Xin; Jia, Weitao; Zhang, Changqing; Huang, Wenhai

2011-07-01

Bioactive borate glass (BG) has good biocompatibility and biodegradation. To investigate the feasibility of bioactive borate glass as a carrier of the antibiotic controlled-releasing by implanting vancomycin-loaded BG (VBG) into the focus of tibia chronic osteomyelitis after debridement. VBG and vancomycin-loaded calcium sulfate (VCS) were prepared with a vancomycin content of 80 mg/g. Sixty-five New Zealand white rabbits, weighing 2.12-3.91 kg (mean, 2.65 kg), were used. The tibia chronic osteomyelitis rabbit models were established by injecting methicillin-resistant Staphylococcus aureus (MRSA, 0.1 mL, 1 x 10(9) cfu/mL) into the right tibia of 65 rabbits. After 3 weeks of injection, 54 rabbits of successful models were randomly divided into groups A (n=11), B (n=11), C (n=16), and D (n=16). Simple debridement was performed in group A; BG, VCS, and VBG were implanted into the infection sites of groups B, C, and D respectively after thorough debridement. A sample of the debrided tissues was harvested for bacterial examination. The vancomycin serum levels were determined in groups C and D at 1, 2, 4, 10, 24, and 48 hours after operation. The boron serum levels were determined in groups B and D at 10, 24, 48, 72, and 120 hours after operation. After 8 weeks, the effectiveness was assessed radiographically, bacteriologically, and histopathologically. Ten rabbits died after operation. No vancomycin was detected in group C; the vancomycin level increased gradually, reached the highest level at 4 hours after operation, and then decreased rapidly in group D. No boron was detected in group B; the boron reached the highest serum level at 10 hours after operation, and then decreased gradually in group D. At 8 weeks, calcium sulfate degraded in group C; BG degraded partially in group D; and no obvious degradation was observed in group B. The repair effect was better in group D than in group C. There was no significant difference in radiograph scoring between groups A, B, C and D (P > 0.05) before operation, but there was significant difference between group D and groups A, B, C (P < 0.05) at 8 weeks after operation. The bacterial culture showed that all the MRSA results were positive in 4 groups. At 8 weeks, the negative rates of MRSA examination were 36.36%, 18.18%, 73.33%, and 81.25% respectively in groups A, B, C, and D, showing significant differences between group D and groups A, B (P < 0.05). The histopathological observation showed that a large number of new bones formed and no foreign body reaction occurred in group D. The histopathologic scores of groups A, B, C, and D were 6.45 +/- 3.62, 7.55 +/- 3.36, 4.27 +/- 2.91, and 3.81 +/- 3.04 respectively, showing significant differences between group D and groups A, B, and between group C and group B (P < 0.05). VBG can improve the repair of bone defect in the treatment of chronic osteomyelitis.

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

PubMed Central

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

2012-01-01

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

Biomechanical evaluation of macro and micro designed screw-type implants: an insertion torque and removal torque study in rabbits.

PubMed

Chowdhary, Ramesh; Jimbo, Ryo; Thomsen, Christian; Carlsson, Lennart; Wennerberg, Ann

2013-03-01

To investigate the combined effect of macro and pitch shortened threads on primary and secondary stability during healing, but before dynamic loading. Two sets of turned implants with different macro geometry were prepared. The test group possessed pitch shortened threads in between the large threads and the control group did not have thread alterations. The two implant groups were placed in both femur and tibiae of 10 lop-eared rabbits, and at the time of implant insertion, insertion torques were recorded. After 4 weeks, all implants were subjected to removal torque tests. The insertion torque values for the control and test groups for the tibia were 15.7 and 20.6 Ncm, respectively, and for the femur, 11.8, and 12.8 Ncm respectively. The removal torque values for the control and test groups in the tibia were 7.9 and 9.1 Ncm, respectively, and for the femur, 7.9 and 7.7 Ncm respectively. There was no statistically significant difference between the control and test groups. Under limited dynamic load, the addition of pitch shortened threads did not significantly improve either the primary or the secondary stability of the implants in bone. © 2011 John Wiley & Sons A/S.

Effects of gentamicin and gentamicin-RGD coatings on bone ingrowth and biocompatibility of cementless joint prostheses: an experimental study in rabbits.

PubMed

Alt, Volker; Bitschnau, Achim; Böhner, Felicitas; Heerich, Katharina Elisabeth; Magesin, Erika; Sewing, Andreas; Pavlidis, Theodoros; Szalay, Gabor; Heiss, Christian; Thormann, Ulrich; Hartmann, Sonja; Pabst, Wolfgang; Wenisch, Sabine; Schnettler, Reinhard

2011-03-01

Antimicrobial coatings are of interest as a means to improve infection prophylaxis in cementless joint arthroplasty. However, those coatings must not interfere with the essential bony integration of the implants. Gentamicin-hydroxyapatite (gentamicin-HA) and gentamicin-RGD (arginine-glycine-aspartate)-HA coatings have recently been shown to significantly reduce infection rates in a rabbit infection prophylaxis model. The purpose of the current study was to investigate the in vitro elution kinetics and in vivo effects of gentamicin-HA and gentamicin-RGD-HA coatings on new bone formation, implant integration and biocompatibility in a rabbit model. In vitro elution testing showed that 95% and 99% of the gentamicin was released after 12 and 24 h, respectively. The in vivo study comprised 45 rabbits in total, with six animals for each of the gentamicin-HA, gentamicin-RGD-HA group and control pure HA coating groups for the 4 week time period, and nine animals for each of the three groups for the 12 week observation period. A 2.0 mm steel K-wire with one of the coatings under test was placed in the intramedullary canal of the tibia. After 4 and 12 weeks the tibiae were harvested and three different areas (proximal metaphysis, shaft area, distal metaphysis) were assessed by quantitative and qualitative histology for new bone formation, direct implant-bone contact and the formation of multinucleated giant cells. The results exhibited high standard deviations in all subgroups. There was a trend towards better bone formation and better direct implant contact in the pure HA coating group compared with both gentamicin coatings after 4 and 12 weeks, which was, however, not statistically significant. The number of multinucleated giant cells did not differ significantly between the three groups at both time points. In summary, both gentamicin coatings with 99% release of gentamicin within 24 h revealed good biocompatibility and bony integration, which was not statistically significant different compared with pure HA coating. Limitations of the study are the high standard deviation of the results and the limited number of animals per time point. Copyright © 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

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

Histological analysis of the alterations on cortical bone channels network after radiotherapy: A rabbit study.

PubMed

Rabelo, Gustavo Davi; Beletti, Marcelo Emílio; Dechichi, Paula

2010-10-01

The aim of this study was to evaluate the effects of radiotherapy in cortical bone channels network. Fourteen rabbits were divided in two groups and test group received single dose of 15 Gy cobalt-60 radiation in tibia, bilaterally. The animals were sacrificed and a segment of tibia was removed and histologically processed. Histological images were taken and had their bone channels segmented and called regions of interest (ROI). Images were analyzed through developed algorithms using the SCILAB mathematical environment, getting percentage of bone matrix, ROI areas, ROI perimeters, their standard deviations and Lacunarity. The osteocytes and empty lacunae were also counted. Data were evaluated using Kolmogorov-Smirnov, Mann Whitney, and Student's t test (P < 0.05). Significant differences in bone matrix percentage, area and perimeters of the channels, their respective standard deviations and lacunarity were found between groups. In conclusion, the radiotherapy causes reduction of bone matrix and modifies the morphology of bone channels network. © 2010 Wiley-Liss, Inc.

Examination of a novel, specified local antibiotic therapy through polymethylmethacrylate capsules in a rabbit osteomyelitis model.

PubMed

Börzsei, László; Mintál, Tibor; Koós, Zoltán; Kocsis, Béla; Helyes, Zsuzsanna; Kereskai, László; Nyárády, József

2006-01-01

Chronic bone and soft tissue suppurations have become more frequent recently due to the increasing number of high-energy injuries. There are certain antibiotic beads available for local administration, but they cannot always be applied specifically against the pyogenic microorganisms. In the present study, a new technique of local antibiotic therapy for the treatment of infections is described. Polymethylmethacrylate (PMMA) capsules were produced and filled with 0.1 ml Tazocin (0.02 g piperacillin sodium + 0.005 g tazobactam). The efficacy of these Tazocin-filled capsules was examined in vivo using a rabbit osteomyelitis model. Chronic osteomyelitis was induced in rabbit tibia by local injection of Staphylococcus aureus. The treatment included surgical debridement and implantation of Tazocin-containing PMMA capsules into the medullar cavity (n = 12). Simple surgical debridement with no antibiotic implantation was performed in control animals (n = 7). Results were evaluated using microbiological, radiological and histological methods 14 weeks after induction of osteomyelitis. Eight weeks after the implantation of PMMA capsules, complete physical, radiological and histological healing was achieved in 7 animals, initiation of the reparative phase was observed histologically in 3 cases and no reparative signs were detected in 2 rabbits. In the control group, no significant sign of reparation could be seen in any of the cases. Copyright 2006 S. Karger AG, Basel.

Immunoproteomic Identification of In Vivo-Produced Propionibacterium acnes Proteins in a Rabbit Biofilm Infection Model.

PubMed

Achermann, Yvonne; Tran, Bao; Kang, Misun; Harro, Janette M; Shirtliff, Mark E

2015-05-01

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. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

In Vivo Degradation Behavior of the Magnesium Alloy LANd442 in Rabbit Tibiae

PubMed Central

Ullmann, Berit; Reifenrath, Janin; Dziuba, Dina; Seitz, Jan-Marten; Bormann, Dirk; Meyer-Lindenberg, Andrea

2011-01-01

In former studies the magnesium alloy LAE442 showed promising in vivo degradation behavior and biocompatibility. However, reproducibility might be enhanced by replacement of the rare earth composition metal “E” by only a single rare earth element. Therefore, it was the aim of this study to examine whether the substitution of “E” by neodymium (“Nd”) had an influence on the in vivo degradation rate. LANd442 implants were inserted into rabbit tibiae and rabbits were euthanized after 4, 8, 13 and 26 weeks postoperatively. In vivo µCT was performed to evaluate the in vivo implant degradation behaviour by calculation of implant volume, density true 3-D thickness and corrosion rates. Additionally, weight loss, type of corrosion and mechanical stability were appraised by SEM/EDS-analysis and three-point bending tests. Implant volume, density and true 3-D thickness decreased over time, whereas the variance of the maximum diameters within an implant as well as the corrosion rate and weight loss increased. SEM examination revealed mainly pitting corrosion after 26 weeks. The maximum bending forces decreased over time. In comparison to LAE442, the new alloy showed a slower, but more uneven degradation behavior and less mechanical stability. To summarize, LANd442 appeared suitable for low weight bearing bones but is inferior to LAE442 regarding its degradation morphology and strength. PMID:28824133

Evaluation of centrifuged bone marrow on bone regeneration around implants in rabbit tibia.

PubMed

Betoni, Walter; Queiroz, Thallita P; Luvizuto, Eloá R; Valentini-Neto, Rodolpho; Garcia-Júnior, Idelmo R; Bernabé, Pedro F E

2012-12-01

To evaluate the bone regeneration of cervical defects produced around titanium implants filled with blood clot and filled with centrifuged bone marrow (CBM) by means of histomorphometric analysis. Twelve rabbits received 2 titanium implants in each right tibia, with the upper cortical prepared with a 5-mm drill and the lower cortex with a 3-mm-diameter drill. Euthanasia was performed to allow analysis at 7, 21, and 60 days after operation. The samples were embedded in light curing resin, cut and stained with alizarin red and Stevenel blue for a histomorphometric analysis of the bone-to-implant contact (BIC) and the bone area around implant (BA). The values obtained were statistically analyzed using the nonparametric Kruskal-Wallis test (P = 0.05). At 60 days postoperation, the groups had their cervical defects completely filled by neoformed bone tissue. There was no statistically significant difference between the groups regarding BIC and BA during the analyzed periods. There was no difference in the bone repair of periimplant cervical defects with or without the use of CBM.

Evaluation of the Surface Treatment on Bone Healing in a Transmucosal 1-mm Area of Implant Abutment: An Experimental Study in the Rabbit Tibia.

PubMed

Gehrke, Sergio Alexandre; da Silva Neto, Ulisses Tavares

2016-06-01

The objective of the present study was to investigate the effect on bone tissue healing patterns in 1-mm area treated in the transmucosal surface of the abutment in the tibia of rabbits. Forty-six abutments were divided into two groups: control group (CG) with 14 abutments with smooth surface and experimental group (EG) with 32 abutments presenting a 1-mm area of the transmucosal surface treated through sandblasting with microparticles of titanium oxide followed by acid etching. Five samples of each group were analyzed using an optical laser profilometer for surface roughness characterization. Thirty-six Morse taper implants (3.5 mm in diameter and 7 mm in length) were inserted 1.5 mm subcrestal into the tibiae of nine rabbits. The implants were removed after 8, 10, and 12 weeks for histological analysis. The histological slides were prepared and analyzed qualitatively in relation to the new bone at the interface bone-abutment and quantitatively, in relation to bone height from the base of the implant. These data were computed and statistically compared inside the groups using analysis of variance and the U-test between groups for same time. Both groups exhibited bone growth in the direction and over the surface of the abutments, with good healing. However, the EG group showed an increased height of bone formation in the crestal direction, and highly significant differences were observed (p < .001) between these measured values. Under the limitations of the present study, histological follow-up at 8, 10, and 12 weeks showed that transmucosal 1-mm area of implant abutment with treatment of the surface facilitated the maintenance of bone height around the abutment compared with the same abutment with the totally smooth surface. © 2015 Wiley Periodicals, Inc.

Bactericidal micron-thin sol-gel films prevent pin tract and periprosthetic infection.

PubMed

Qu, Haibo; Knabe, Christine; Burke, Megan; Radin, Shula; Garino, Jonathan; Schaer, Thomas; Ducheyne, Paul

2014-08-01

Orthopedic injuries constitute the majority of wounds sustained by U.S. soldiers in recent conflicts. The risk of infection is considerable with fracture fixation devices. In this pilot study, we examined the use of unique bactericidal micron-thin sol-gel films on fracture fixation devices and their ability to prevent and eradicate infections. External fixation was studied with micron-thin sol-gel coated percutaneous pins releasing triclosan and inserted medially into rabbit tibiae. A total of 11 rabbits received percutaneous pins that were either uncoated or sol-gel/triclosan coated. Internal fracture fixation was also studied using sol-gel coated intramedullary (IM) nails releasing vancomycin in the intramedullary tibiae. Six sheep received IM nails that were coated with a sol-gel film that either contained vancomycin or did not contain vancomycin. All animals were challenged with Staphylococcus aureus around the implant. Animals were euthanized at 1 month postoperative. Rabbits receiving triclosan/sol-gel coated percutaneous pins did not show signs of infection. Uncoated percutaneous pins had a significantly higher infection rate. In the sheep study, there were no radiographic signs of osteomyelitis with vancomycin/sol-gel coated IM nails, in contrast to the observations in the control cohort. Hence, the nanostructured sol-gel controlled release technology offers the promise of a reliable and continuous delivery system of bactericidals from orthopedic devices to prevent and treat infection. Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.

Allografts with autogenous platelet-rich plasma for tibial defect reconstruction: a rabbit study.

PubMed

Nather, Aziz; Wong, Keng Lin; David, Vikram; Pereira, Barry P

2012-12-01

To evaluate the effect of autogenous platelet-rich plasma (PRP) for fresh-frozen allografts in tibial defect reconstruction in rabbits. 40 adult New Zealand white rabbits underwent tibial defect reconstruction with autografts (n=12), allografts without PRP (n=12), or allografts with PRP (n=12) and were observed for 12, 16, and 24 weeks (4 for each period). Tibias of the remaining 4 rabbits were used as donor allografts, and the remaining allografts were procured from recipient rabbits. A 1.5- cm cortical segment of the tibia was osteotomised, and then fixed with a 9-hole mini-compression plate and 2 cerclage wires. Allografts were stripped off the periosteum and soft tissues and medullary contents, and then stored in a freezer at -80 ºC. All allografts were deep frozen for at least 4 weeks before transplantation. 7 ml of whole blood was drawn to prepare 1 ml of PRP. The PRP was then mixed with 1.0 ml of human thrombin to form a platelet gel. The PRP gel was then packed into the medullary canal of the allograft and applied on the cortical surface before tibial defect reconstruction. Rabbits were sacrificed at 12, 16, and 24 weeks. The specimens were assessed for bone union at host-graft junctions and for bone resorption, new bone formation, callus encasement, and viable osteocyte counts. There were 4 specimens in each group at each observation period. Osteoid bridging the gap at host-graft junctions was noted in all specimens in the autograft and allograft-with-PRP groups at week 12 and in the allograft-without-PRP group at week 24. Bone union in allografts without PRP was delayed. All indices for biological incorporation (resorption index, new bone formation index, callus encasement index, and viable osteocyte count) were significantly greater in the autograft than allograft-without-PRP groups, except for the resorption index at week 24, whereas the differences were not significant between the autograft and allograft-with-PRP groups. The differences between the 2 allograft groups were usually not significant, except for the resorption index. PRP-augmented allografts behaved similarly to autografts for tibial defect reconstruction in rabbits. PRP increased bone union and bone resorption.

Effect of low-intensity pulsed ultrasound stimulation on gap healing in a rabbit osteotomy model evaluated by quantitative micro-computed tomography-based cross-sectional moment of inertia.

PubMed

Tobita, Kenji; Matsumoto, Takuya; Ohashi, Satoru; Bessho, Masahiko; Kaneko, Masako; Ohnishi, Isao

2012-07-01

It has been previously demonstrated that low-intensity pulsed ultrasound stimulation (LIPUS) enhances formation of the medullary canal and cortex in a gap-healing model of the tibia in rabbits, shortens the time required for remodeling, and enhances mineralization of the callus. In the current study, the mechanical integrity of these models was confirmed. In order to do this, the cross-sectional moment of inertia (CSMI) obtained from quantitative micro-computed tomography scans was calculated, and a comparison was made with a four-point bending test. This parameter can be analyzed in any direction, and three directions were selected in order to adopt an XYZ coordinate (X and Y for bending; Z for torsion). The present results demonstrated that LIPUS improved earlier restoration of bending stiffness at the healing site. In addition, LIPUS was effective not only in the ultrasound-irradiated plane, but also in the other two planes. CSMI may provide the structural as well as compositional determinants to assess fracture healing and would be very useful to replace the mechanical testing.

Effect of calcium phosphate surface coating on bone ingrowth onto porous-surfaced titanium alloy implants in rabbit tibiae.

PubMed

Yang, Cheng

2002-04-01

The purpose of the present study was to determine whether calcium phosphate coating has a significant impact on bone ingrowth into a porous titanium implant. Porous-surfaced titanium alloy Ti-6Al-4V implants were prepared with or without the addition of a thin surface layer of calcium phosphate applied by sol-gel coating. Implants were placed into the tibiae of 16 rabbits. Implanted sites were allowed to heal for 2 weeks, after which specimens were retrieved for morphometric assessment using backscatter scanning electron microscopy. The data collected show that there is more extensive ingrowth into the porous regions of the calcium phosphate-coated implants than into the control implants. The weighted average ingrowth for the calcium phosphate-coated implants was 2.01, whereas that for the noncoated implants was 1.49; the difference is statistically significant (P <.01). The addition of a thin layer of calcium phosphate to these implants appears to promote a more extensive implant-to-bone interface by allowing the neck regions to become intimately ingrown with bone even after only 2 weeks of initial healing. Copyright 2002 American Association of Oral and Maxillofacial Surgeons

Peri-implant and systemic effects of high-/low-affinity bisphosphonate-hydroxyapatite composite coatings in a rabbit model with peri-implant high bone turnover

PubMed Central

2012-01-01

Background Hydroxyapatite (HA) coatings composed with bisphosphonates (BPs) which have high mineral-binding affinities have been confirmed to successfully enhance implant stability. However, few previous studies focused on HA coatings composed with low-affinity BPs or on systemic effects of locally released BPs. Methods In this long-term study, we developed two kinds of BP-HA composite coatings using either high-affinity BP (alendronate, ALN) or low-affinity BP (risedronate, RIS). Thirty-six rabbits were divided into three groups according to different coating applications (group I: HA, group II: ALN-HA, and group III: RIS-HA). Implants were inserted into the proximal region of the medullary cavity of the left tibiay. At insertion, 2 × 108 wear particles were injected around implants to induce a peri-implant high bone turnover environment. Both local (left tibias) and systemic (right tibias and lumbar vertebrae) inhibitory effect on bone resorption were compared, including bone-implant integration, bone architecture, bone mineral density (BMD), implant stability, and serum levels of bone turnover markers. Results The results indicated that ALN-HA composite coating, which could induce higher bone-implant contact (BIC) ratio, bone mass augmentation, BMD, and implant stability in the peri-implant region, was more potent on peri-implant bone, while RIS-HA composite coating, which had significant systemic effect, was more potent on non-peri-implant bone, especially lumbar vertebrae. Conclusions It is instructive and meaningful to further clinical studies that we could choose different BP-HA composite coatings according to the patient’s condition. PMID:22686414

Characteristics of bone fractures and usefulness of micro-computed tomography for fracture detection in rabbits: 210 cases (2007-2013).

PubMed

Sasai, Hiroshi; Fujita, Daisuke; Tagami, Yukari; Seto, Eiko; Denda, Yuki; Hamakita, Hideaki; Ichihashi, Tomonori; Okamura, Kensaku; Furuya, Masaru; Tani, Hiroyuki; Sasai, Kazumi; Yamate, Jyoji

2015-06-15

To characterize bone fractures and the usefulness of micro-CT for imaging fractures in pet rabbits. Retrospective case series. 210 client-owned rabbits with bone fractures. Medical records of rabbits evaluated for bone fractures from 2007 through 2013 were examined. Information was collected on signalment and nature of fractures, and radiographic and micro-CT images of fractures were reviewed. Almost half (n = 95 [47.7%]) of fractures were in rabbits < 3 years old. Accidental fall was the most common cause. Vertebral fracture was the most common type of fracture with a nonneoplastic cause (n = 46 [23.2%]) and was most common in the L4-L7 region. The tibia was the most common site for limb fracture among all fractures with a nonneoplastic cause (45 [22.7%]). Twelve (5.7%) fractures had a neoplastic cause, and 7 of these were associated with metastatic uterine adenocarcinoma. Females were significantly more likely to have a fracture caused by neoplasia than were males. Compared with radiography, micro-CT provided more detailed fracture information, particularly for complicated fractures or structures (eg, skull, pelvic, vertebral, and comminuted limb fractures). Findings were useful for understanding the nature of fractures in pet rabbits and supported the use of micro-CT versus radiography for fracture detection and evaluation.

Bone response to hydroxyapatites with open porosity of animal origin (porcine [OsteoBiol mp3] and bovine [Endobon]): a radiological and histomorphometric study.

PubMed

Ramírez-Fernández, MaPiedad; Calvo-Guirado, Jose Luis; Delgado-Ruiz, Rafael Arcesio; Maté-Sánchez Del Val, José Eduardo; Vicente-Ortega, Vicente; Meseguer-Olmos, Luis

2011-07-01

To carry out a radiological and histomorphometric evaluation of bone response to two xenografts of animal origin, one porcine, and the other bovine, inserted in rabbits' tibiae. Twenty New Zealand rabbits weighing 3900-4500 g were used. Twenty bovine bone grafts (Endobon) in granulated form of 500-1000 μm granulometry were inserted in the proximal metaphyseal area of the animals' right tibia, and 20 porcine bone grafts (OsteoBiol mp3) in granulated form of 600-1000 μm granulometry were inserted in the proximal metaphyseal area of the animals' left tibia. Following graft insertion, the animals were sacrificed in four groups of five, after 1, 2, 3 and 4 months, respectively. Anteroposterior and lateral radiographs were taken. Samples were processed for observation under light microscopy. Histomorphometric measurements were presented as mean values ± standard deviations. At 4 months after treatment, the bone defects displayed radiological images that showed complete repair of osseous defects. Histomorphometric evaluation showed that for the porcine xenograft, the study averages for newly formed bone represented 22.8 ± 1.8%, for residual graft material 23.6 ± 3% and for connective tissue 53.5 ± 2.5%, while for the bovine xenograft newly formed bone represented 23.1 ± 1.8%, residual graft material 39.4 ± 3% and non-mineralized connective tissue 37.5 ± 2.5%. The biomaterials assessed in the study were shown to be biocompatible and osteoconductive. Collagenized porcine xenografts proved more resorbable than bovine xenografts. Both can be used as possible bone substitutes without interfering with normal reparative bone processes. © 2011 John Wiley & Sons A/S.

Safety and clinical effectiveness of a compounded sustained-release formulation of buprenorphine for postoperative analgesia in New Zealand White rabbits.

PubMed

DiVincenti, Louis; Meirelles, Luiz A D; Westcott, Robin A

2016-04-01

To determine the clinical effectiveness and safety of a compounded sustained-release formulation of buprenorphine, compared with effects of regular buprenorphine, for postoperative analgesia in rabbits. Blinded randomized controlled clinical trial. 24 purpose-bred adult male New Zealand White rabbits. Rabbits received titanium implants in each tibia as part of another study. Immediately prior to surgery, each rabbit received regular buprenorphine hydrochloride (0.02 mg/kg [0.009 mg/lb], SC, q 12 h for 3 days) or 1 dose of a compounded sustained-release formulation of buprenorphine (0.12 mg/kg [0.055 mg/lb], SC) followed by an equal volume of saline (0.9% NaCl) solution (SC, q 12 h for 3 days) after surgery. For 7 days after surgery, rabbits were evaluated for signs of pain by means of rabbit grimace and activity scoring and for adverse effects. No significant differences were identified between treatment groups in grimace and activity scores at any point. No major adverse effects were detected for either drug. However, 3 rabbits that received regular buprenorphine had pain scores suggestive of moderate to severe pain by the time dose administration was due (ie, within the 12-hour administration interval). No clinically important differences were detected in intraoperative anesthetic or postoperative recovery variables. Sustained-release buprenorphine administered SC at 0.12 mg/kg was at least as effective as regular buprenorphine in providing analgesia for rabbits following orthopedic surgery without any major adverse effects. This sustained-release formulation represents an important alternative for rabbit analgesia with potential to improve rabbit welfare over existing analgesic standards.

Experimental model of bone response to collagenized xenografts of porcine origin (OsteoBiol® mp3): a radiological and histomorphometric study.

PubMed

Calvo Guirado, Jose Luis; Ramírez Fernández, Maria Piedad; Negri, Bruno; Delgado Ruiz, Rafael Arcesio; Maté Sánchez de-Val, José Eduardo; Gómez-Moreno, Gerardo

2013-02-01

Adequate alveolar ridges are fundamental to successful rehabilitation with implants. There are diverse techniques for reconstructing atrophied ridges, of which bone substitute grafts is one possibility. The aim of this study was to carry out radiological and histomorphometric evaluations of bone response to collagenized porcine bone xenografts over a 4-month period following their insertion in rabbits' tibiae. Twenty New Zealand rabbits were used. Twenty collagenized porcine bone xenografts (Osteobiol® mp3, Tecnoss Dental s.r.l., Torino, Italy), in granulated form of 600 to 1,000 µm, were inserted in the proximal metaphyseal area of the animals' tibiae and 20 control areas were created. Following implantation, the animals were sacrificed in four groups of five, after 1, 2, 3, and 4 months, respectively. Radiological and histomorphometric studies were made. After 4 months, radiological images revealed bone defects with a decrease in graft volume and the complete repair of the osseous defect. No healed or residual bone alterations attributable to the presence of the implants were observed. Histomorphometric analysis at 4 months found mean values for newly formed bone, residual graft material, and non-mineralized connective tissue of 25.4 ± 1.8%, 36.37 ± 3.0%, and 38.22 ± 2.5%, respectively. There were no statistical differences in the length of cortical formation with collagenized porcine xenograft (98.9 ± 1.1%) compared with the control samples (99.1 ± 0.7%) at the end of the study period. The biomaterial used proved to be biocompatible, bioabsorbable, and osteoconductive and as such, a possible bone substitute that did not interfere with the bone's normal reparative processes. © 2011 Wiley Periodicals, Inc.

Guided Bone Regeneration in Long-Bone Defects with a Structural Hydroxyapatite Graft and Collagen Membrane

DTIC Science & Technology

2013-01-01

Praetorius, F. Guided tissue regeneration using de- gradable and nondegradable membranes in rabbit tibia. Clin Oral Implants Res 4, 172, 1993. 8. Queiroz... Regeneration of periodontal tissues : combinations of barrier membranes and grafting materials–biological foundation and preclinical evi- dence: a...structural graft provides benefits for bone tissue regeneration in terms of early interfacial integration. Introduction The treatment of large-bone defects

In vivo biocompatibility of new nano-calcium-deficient hydroxyapatite/poly-amino acid complex biomaterials.

PubMed

Dai, Zhenyu; Li, Yue; Lu, Weizhong; Jiang, Dianming; Li, Hong; Yan, Yonggang; Lv, Guoyu; Yang, Aiping

2015-01-01

To evaluate the compatibility of novel nano-calcium-deficient hydroxyapatite/poly-amino acid (n-CDHA/PAA) complex biomaterials with muscle and bone tissue in an in vivo model. Thirty-two New Zealand white rabbits were used in this study. Biomaterials were surgically implanted into each rabbit in the back erector spinae and in tibia with induced defect. Polyethylene was implanted into rabbits in the control group and n-CDHA/PAA into those of the experimental group. Animals were examined at four different points in time: 2 weeks, 4 weeks, 12 weeks, and 24 weeks after surgery. They were euthanized after embolization. Back erector spinae muscles with the surgical implants were examined after hematoxylin and eosin (HE) staining at these points in time. Tibia bones with the surgical implants were examined by X-ray and scanning electron microscopy (SEM) at these points in time to evaluate the interface of the bone with the implanted biomaterials. Bone tissues were sectioned and subjected to HE, Masson, and toluidine blue staining. HE staining of back erector spinae muscles at 4 weeks, 12 weeks, and 24 weeks after implantation of either n-CDHA/PAA or polyethylene showed disappearance of inflammation and normal arrangement in the peripheral tissue of implant biomaterials; no abnormal staining was observed. At 2 weeks after implantation, X-ray imaging of bone tissue samples in both experimental and control groups showed that the peripheral tissues of the implanted biomaterials were continuous and lacked bone osteolysis, absorption, necrosis, or osteomyelitis. The connection between implanted biomaterials and bone tissue was tight. The results of HE, Masson, toluidine blue staining and SEM confirmed that the implanted biomaterials were closely connected to the bone defect and that no rejection had taken place. The n-CDHA/PAA biomaterials induced differentiation of a large number of chondrocytes. New bone trabecula began to form at 4 weeks after implanting n-CDHA/PAA biomaterials, and lamellar bone gradually formed at 12 weeks and 24 weeks after implantation. Routine blood and kidney function tests showed no significant changes at 2 weeks and 24 weeks after implantation of both biomaterials. n-CDHA/PAA composites showed good compatibility in in vivo model. In this study, n-CDHA/PAA were found to be safe, nontoxic, and biologically active in bone repair.

In vivo biocompatibility of new nano-calcium-deficient hydroxyapatite/poly-amino acid complex biomaterials

PubMed Central

Dai, Zhenyu; Li, Yue; Lu, Weizhong; Jiang, Dianming; Li, Hong; Yan, Yonggang; Lv, Guoyu; Yang, Aiping

2015-01-01

Objective To evaluate the compatibility of novel nano-calcium-deficient hydroxyapatite/poly-amino acid (n-CDHA/PAA) complex biomaterials with muscle and bone tissue in an in vivo model. Methods Thirty-two New Zealand white rabbits were used in this study. Biomaterials were surgically implanted into each rabbit in the back erector spinae and in tibia with induced defect. Polyethylene was implanted into rabbits in the control group and n-CDHA/PAA into those of the experimental group. Animals were examined at four different points in time: 2 weeks, 4 weeks, 12 weeks, and 24 weeks after surgery. They were euthanized after embolization. Back erector spinae muscles with the surgical implants were examined after hematoxylin and eosin (HE) staining at these points in time. Tibia bones with the surgical implants were examined by X-ray and scanning electron microscopy (SEM) at these points in time to evaluate the interface of the bone with the implanted biomaterials. Bone tissues were sectioned and subjected to HE, Masson, and toluidine blue staining. Results HE staining of back erector spinae muscles at 4 weeks, 12 weeks, and 24 weeks after implantation of either n-CDHA/PAA or polyethylene showed disappearance of inflammation and normal arrangement in the peripheral tissue of implant biomaterials; no abnormal staining was observed. At 2 weeks after implantation, X-ray imaging of bone tissue samples in both experimental and control groups showed that the peripheral tissues of the implanted biomaterials were continuous and lacked bone osteolysis, absorption, necrosis, or osteomyelitis. The connection between implanted biomaterials and bone tissue was tight. The results of HE, Masson, toluidine blue staining and SEM confirmed that the implanted biomaterials were closely connected to the bone defect and that no rejection had taken place. The n-CDHA/PAA biomaterials induced differentiation of a large number of chondrocytes. New bone trabecula began to form at 4 weeks after implanting n-CDHA/PAA biomaterials, and lamellar bone gradually formed at 12 weeks and 24 weeks after implantation. Routine blood and kidney function tests showed no significant changes at 2 weeks and 24 weeks after implantation of both biomaterials. Conclusion n-CDHA/PAA composites showed good compatibility in in vivo model. In this study, n-CDHA/PAA were found to be safe, nontoxic, and biologically active in bone repair. PMID:26504382

Bone-bonding behavior of alumina bead composite.

PubMed

Shinzato, S; Kobayashi, M; Choju, K; Kokubo, T; Nakamura, T

1999-08-01

Previously we developed an alumina bead composite (ABC) consisting of alumina bead powder (AL-P) and bisphenol-alpha-glycidyl methacrylate (Bis-GMA)-based resin and reported its excellent osteoconductivity in rat tibiae. In the present study, are evaluated histologically and mechanically the effect of alumina crystallinity on the osteoconductivity and bone-bonding strength of the composite. AL-P was manufactured by fusing crushed alpha-alumina powder and quenching it. The AL-P was composed mainly of amorphous and delta-crystal phases of alumina. Its average particle size was 3.5 microm, and it took a spherical form. Another composite (alpha ALC), filled with pure alpha-alumina powder (alpha AL-P), was used as a referential material. The proportion of powder added to each composite was 70% w/w. Mechanical testing of ABC and alpha ALC indicated that they would be strong enough for use under weight-bearing conditions. The affinity indices for ABC, determined using male Wistar rat tibiae, were significantly higher than those for alpha ALC (p < 0.0001) up to 8 weeks. Composite plates (15 x 10 x 2 mm) that had an uncured surface layer on one side were made in situ in a rectangular mold. One of the plates was implanted into the proximal metaphysis of the tibia of a male Japanese white rabbit, and the failure load was measured by a detaching test 10 weeks after implantation. The failure loads for ABC on its uncured surface [1.91+/-1.23 kgf (n = 8)] were significantly higher than those for alpha ALC on its uncured surface [0.35+/-0.33 kgf (n = 8); (p < 0.0001)], and they also were significantly higher than those for ABC on the other (cured surface) side (p < 0.0001). Histological examinations using rabbit tibiae revealed bone ingrowth into the composite only on the uncured surface of ABC. This study revealed that the amorphous phase of alumina and formation of an uncured surface layer are needed for the osteoconductive and bone-bonding ability of ABC. ABC shows promise as a basis for the development of a highly osteoconductive and mechanically strong biomaterial.

Influence of Chromium-Cobalt-Molybdenum Alloy (ASTM F75) on Bone Ingrowth in an Experimental Animal Model.

PubMed

Zuchuat, Jésica; Berli, Marcelo; Maldonado, Ysaí; Decco, Oscar

2017-12-26

Cr-Co-Mo (ASTM F75) alloy has been used in the medical environment, but its use as a rigid barrier membrane for supporting bone augmentation therapies has not been extensively investigated. In the present study, Cr-Co-Mo membranes of different heights were placed in New Zealand white, male rabbit tibiae to assess the quality and volume of new bone formation, without the use of additional factors. Animals were euthanized at 20, 30, 40, and 60 days. Bone formation was observed in all of the cases, although the tibiae implanted with the standard membranes reached an augmentation of bone volume that agreed with the density values over the timecourse. In all cases, plasmatic exudate was found under the membrane and in contact with the new bone. Histological analysis indicated the presence of a large number of chondroblasts adjacent to the inner membrane surface in the first stages, and osteoblasts and osteocytes were observed under them. The bone formation was appositional. The Cr-Co-Mo alloy provides a scaffold with an adequate microenvironment for vertical bone volume augmentation, and the physical dimensions and disposition of the membrane itself influence the new bone formation.

Influence of Chromium-Cobalt-Molybdenum Alloy (ASTM F75) on Bone Ingrowth in an Experimental Animal Model

PubMed Central

Zuchuat, Jésica; Berli, Marcelo; Maldonado, Ysaí; Decco, Oscar

2017-01-01

Cr-Co-Mo (ASTM F75) alloy has been used in the medical environment, but its use as a rigid barrier membrane for supporting bone augmentation therapies has not been extensively investigated. In the present study, Cr-Co-Mo membranes of different heights were placed in New Zealand white, male rabbit tibiae to assess the quality and volume of new bone formation, without the use of additional factors. Animals were euthanized at 20, 30, 40, and 60 days. Bone formation was observed in all of the cases, although the tibiae implanted with the standard membranes reached an augmentation of bone volume that agreed with the density values over the timecourse. In all cases, plasmatic exudate was found under the membrane and in contact with the new bone. Histological analysis indicated the presence of a large number of chondroblasts adjacent to the inner membrane surface in the first stages, and osteoblasts and osteocytes were observed under them. The bone formation was appositional. The Cr-Co-Mo alloy provides a scaffold with an adequate microenvironment for vertical bone volume augmentation, and the physical dimensions and disposition of the membrane itself influence the new bone formation. PMID:29278372

Comparison of removal torques between laser-etched and modified sandblasted acid-etched Ti implant surfaces in rabbit tibias

PubMed Central

Al Awamleh, Abdel Ghani Ibrahim

2018-01-01

PURPOSE The purpose of this study was to analyze the effects of two different implant surface treatments on initial bone connection by comparing the Removal Torque Values (RTQs) at 7 and 10 days after chemically modified, sandblasted, large-grit and acid-etched (modSLA), and Laser-etched (LE) Ti implant placements. MATERIALS AND METHODS Twenty modSLA and 20 LE implants were installed on the left and right tibias of 20 adult rabbits. RTQs were measured after 7 and 10 days in 10 rabbits each. Scanning electron microscope (SEM) photographs of the two implants were observed by using Quanta FEG 650 from the FEI company (Hillsboro, OR, USA). Analyses of surface elements and components were conducted using energy dispersive spectroscopy (EDS, Horiba, Kyoto, Japan). RESULTS The mean RTQs were 12.29 ± 0.830 and 12.19 ± 0.713 Ncm after 7 days (P=.928) and 16.47 ± 1.324 and 16.17 ± 1.165 Ncm after 10 days (P=.867) for LE and modSLA, respectively, indicating no significant inter-group differences. Pore sizes in the LE were 40 µm and consisted of numerous small pores, whereas pore sizes in the modSLA were 5 µm. In the EDS analysis, Ti, O, and C were the only three elements found in the LE surfaces. Na, Ca, Cl, and K were also observed in modSLA, in addition to Ti, O, and C. CONCLUSION The implants showed no significant difference in biomechanical bond strength to bone in early-stage osseointegration. LE implant can be considered an excellent surface treatment method in addition to the modSLA implant and can be applied to the early loading of the prosthesis clinically. PMID:29503717

Comparison of removal torques between laser-treated and SLA-treated implant surfaces in rabbit tibiae

PubMed Central

Kang, Nam-Seok; Li, Lin-Jie

2014-01-01

PURPOSE The purpose of this study was to compare removal torques and surface topography between laser treated and sandblasted, large-grit, acid-etched (SLA) treated implants. MATERIALS AND METHODS Laser-treated implants (experimental group) and SLA-treated implants (control group) 8 mm in length and 3.4 mm in diameter were inserted into both sides of the tibiae of 12 rabbits. Surface analysis was accomplished using a field emission scanning electron microscope (FE-SEM; Hitachi S-4800; Japan) under ×25, ×150 and ×1,000 magnification. Surface components were analyzed using energy dispersive spectroscopy (EDS). Rabbits were sacrificed after a 6-week healing period. The removal torque was measured using the MGT-12 digital torque meter (Mark-10 Co., Copiague, NY, USA). RESULTS In the experimental group, the surface analysis showed uniform porous structures under ×25, ×150 and ×1,000 magnification. Pore sizes in the experimental group were 20-40 mm and consisted of numerous small pores, whereas pore sizes in the control group were 0.5-2.0 mm. EDS analysis showed no significant difference between the two groups. The mean removal torque in the laser-treated and the SLA-treated implant groups were 79.4 Ncm (SD = 20.4; range 34.6-104.3 Ncm) and 52.7 Ncm (SD = 17.2; range 18.7-73.8 Ncm), respectively. The removal torque in the laser-treated surface implant group was significantly higher than that in the control group (P=.004). CONCLUSION In this study, removal torque values were significantly higher for laser-treated surface implants than for SLA-treated surface implants. PMID:25177474

Assessment of the influence of Laser phototherapy on the bone repair process of complete fractures in tibiae of rabbits stabilized with semi-rigid internal fixation treated with or without MTA graft: a histological study

NASA Astrophysics Data System (ADS)

Soares, Luiz G. P.; Silva, Aline C. P.; Silva, Anna Paula L. T.; Neves, Bruno Luiz R. C.; Santos, Nicole R. S.; dos Santos, Jean N.; Pinheiro, Antonio L. B.

2016-03-01

Beside biomaterials, Laser phototherapy has shown positive effects as auxiliary therapy in bone repair process, especially when involving large bone losses. The aim of this histological study was to evaluate, by light microscopy, the influence of laser phototherapy on the repair of complete tibial fractures in rabbits treated or not with semi-rigid internal fixation and Mineral Trioxide Aggregate - MTA graft. Twelve Rabbits were randomly divided into four groups with three animals each. After general anesthesia, complete fractures were created in one tibia with a carborundum disk. All animals (groups I-IV) had the fracture stabilized with semi-rigid fixation (wire osteosynthesis - WO). Group I was routinely fixed with WO; groups II and IV fracture was filled by blood clot and MTA implant. In Groups III and IV fracture was filled by blood clot and further irradiated with laser (λ780 nm, 70 mW, CW, Φ = 0.04 cm2, 20.4 J/cm2, per session, t = 300s, 142.8 J/cm2 per treatment). The phototherapy protocol was applied immediately after the surgery and repeated each 48 hours during 15 days. Animal death occurred on the 30th postoperative day. After removal of the specimens, the samples were routinely processed, stained with HE and evaluated by light microscopy. Histologically, the group treated with MTA graft and irradiated with laser showed the fracture filled by a more organized and mature trabecular bone, when compared with all other groups. From the results of the present study, it may be concluded that the association of Laser phototherapy + MTA graft in fractures treated with WO improved bone repair when compared with fractures treated only with WO.

Bone regeneration in experimental animals using calcium phosphate cement combined with platelet growth factors and human growth hormone.

PubMed

Emilov-Velev, K; Clemente-de-Arriba, C; Alobera-García, M Á; Moreno-Sansalvador, E M; Campo-Loarte, J

2015-01-01

Many substances (growth factors and hormones) have osteoinduction properties and when added to some osteoconduction biomaterial they accelerate bone neoformation properties. The materials included 15 New Zealand rabbits, calcium phosphate cement (Calcibon(®)), human growth hormone (GH), and plasma rich in platelets (PRP). Each animal was operated on in both proximal tibias and a critical size bone defect of 6mm of diameter was made. The animals were separated into the following study groups: Control (regeneration only by Calcibon®), PRP (regeneration by Calcibon® and PRP), GH (regeneration by Calcibon® and GH). All the animals were sacrificed at 28 days. An evaluation was made of the appearance of the proximal extreme of rabbit tibiae in all the animals, and to check the filling of the critical size defect. A histological assessment was made of the tissue response, the presence of new bone formation, and the appearance of the biomaterial. Morphometry was performed using the MIP 45 image analyser. ANOVA statistical analysis was performed using the Statgraphics software application. The macroscopic appearance of the critical defect was better in the PRP and the GH group than in the control group. Histologically greater new bone formation was found in the PRP and GH groups. No statistically significant differences were detected in the morphometric study between bone formation observed in the PRP group and the control group. Significant differences in increased bone formation were found in the GH group (p=0.03) compared to the other two groups. GH facilitates bone regeneration in critical defects filled with calcium phosphate cement in the time period studied in New Zealand rabbits. Copyright © 2014 SECOT. Published by Elsevier Espana. All rights reserved.

Evaluation of carbonate apatite blocks fabricated from dicalcium phosphate dihydrate blocks for reconstruction of rabbit femoral and tibial defects.

PubMed

Kanazawa, Masayuki; Tsuru, Kanji; Fukuda, Naoyuki; Sakemi, Yuta; Nakashima, Yasuharu; Ishikawa, Kunio

2017-06-01

This study aimed to evaluate in vivo behavior of a carbonate apatite (CO 3 Ap) block fabricated by compositional transformation via a dissolution-precipitation reaction using a calcium hydrogen phosphate dihydrate [DCPD: CaHPO 4 ·2H 2 O] block as a precursor. These blocks were used to reconstruct defects in the femur and tibia of rabbits, using sintered dense hydroxyapatite (HAp) blocks as the control. Both the CO 3 Ap and HAp blocks showed excellent tissue response and good osteoconductivity. HAp block maintained its structure even after 24 weeks of implantation, so no bone replacement of the implant was observed throughout the post-implantation period in either femoral or tibial bone defects. In contrast, CO 3 Ap was resorbed with increasing time after implantation and replaced with new bone. The CO 3 Ap block was resorbed approximately twice as fast at the metaphysis of the proximal tibia than at the epiphysis of the distal femur. The CO 3 Ap block was resorbed at an approximately linear change over time, with complete resorption was estimated by extrapolation of data at approximately 1-1.5 years. Hence, the CO 3 Ap block fabricated in this study has potential value as an ideal artificial bone substitute because of its resorption and subsequent replacement by bone.

Modeling and analysis of elastic fields in tibia and fibula

NASA Astrophysics Data System (ADS)

Ghosh, M.; Chowdhury, B. U.; Parvej, M. S.; Afsar, A. M.

2017-12-01

In this study, stress analysis of tibia and fibula subjected to body weight in static condition was carried out. The tibia and fibula were fabricated by casting process. A 3-D solid model of tibia and fibula was developed in SolidWorks by using the geometry of cross sections at different locations of the fabricated tibia and fibula. The 3-D model was analyzed by ANSYS to evaluate the stress, strain, and deformation for identifying the critical sections of tibia and fibula. It is found that, in terms of deformation, the critical zone is the contact zone between tibia-fibula and patella. However, in terms of stress, the critical zone is located on fibula between 25% and 40% height from the lower mating portion of the tibia and fibula.

The impact of zoledronic acid on regenerate and native bone after consolidation and removal of the external fixator: an animal model study.

PubMed

Saghieh, Said; Khoury, Nabil J; Tawil, Ayman; Masrouha, Karim Z; Musallam, Khaled M; Khalaf, Kinda; Dosh, Laura; Jaouhari, Rosemarie Reich; Birjawi, Ghina; El-Hajj-Fuleihan, Ghada

2010-02-01

We investigated the role of zoledronic acid on the regenerate and native bone after consolidation and removal of the external fixator in a rabbit model of distraction osteogenesis using 28 New Zealand white rabbits. The rabbits were randomly distributed into two groups. The first group received three doses of zoledronic acid (ZA) 0.1 mg/kg subcutaneously at weekly intervals while the second group received injections of sterile saline. Distraction started on day 7 at a rate of 0.8 mm/day for 12 days. At week 3 the average lengthening, regenerate density, and regenerate continuity were comparable between the two groups. At week 11 the regenerate in the treated group had a significant increase in Bone Mineral Density (BMD) and Bone Mineral Content (BMC) compared to the placebo group. On axial compression, the regenerate showed an increase in the peak load and a higher modulus of elasticity in the treated group. At 6 months, radiographs demonstrated signs of osteopenia of the proximal metaphysis in the control group, and failure of new bone formation around the pin sites in the treated group. BMC and BMD value differences between the two groups were not statistically significant. Histologically, there was persistence of more bone trabeculae in the medullary canal of the regenerate with the persistence of the pin-holes in the treated group. Mechanically, the regenerates in the treated group remain stronger in resisting the axial compression. The proximal fragment in the treated group exhibited a statistically significant decrease in the peak load, toughness and efail %. In conclusion, bisphosphonate-treated rabbits have a stronger regenerate during distraction, and directly after removal of the fixator. They do not develop disuse osteopenia in their lengthened tibia. This treatment may shorten the time in the external fixator and prevent fragility fractures in the treated extremity. However, its long-term safety has not yet been established. (c) 2009 Elsevier Inc. All rights reserved.

Bone bonding in bioactive glass ceramics combined with a new synthesized agent TAK-778.

PubMed

Kato, H; Neo, M; Tamura, J; Nakamura, T

2001-11-01

We studied the stimulatory effects of TAK-778, a new synthetic 3-benzothiepin derivative that promotes osteoblast differentiation, in the bonding of bone to bioactive glass ceramic implants in rabbit tibiae. Smooth-surfaced, rectangular plates (15 x 10 x 2 mm) made of apatite-wollastonite-containing glass ceramic were implanted bilaterally into the proximal metaphyses of rabbit tibiae. Sustained-release microcapsules containing TAK-778 were packed into the medullary cavity in one limb and untreated microcapsules were packed into the contralateral limb to serve as a paired control. At 4, 8, and 16 weeks after implantation, bonding at the bone/implant interfaces was evaluated using a detaching test and histological examination of undecalcified specimens. The tensile failure load increased during weeks 4 to 16 in both groups; the tensile failure load in the TAK-778-treated group was significantly greater than that in the control group at each interval after implantation. Histologically, the TAK-778-treated specimens showed greater active new bone formation mainly in the medullary cavity and more extensive bonding between the implant and bone than the untreated specimens. The results of this study suggest that adding the bone formation-promoting TAK-778 to bioactive glass ceramic implants may significantly accelerate bone apposition to the implants and improve the bonding process at the interface. This would help to establish earlier and stronger bonding of orthopedic ceramic implants to the surrounding bone tissue. Copyright 2001 John Wiley & Sons, Inc.

Comparison of Borate Bioactive Glass and Calcium Sulfate as Implants for the Local Delivery of Teicoplanin in the Treatment of Methicillin-Resistant Staphylococcus aureus-Induced Osteomyelitis in a Rabbit Model

PubMed Central

Jia, Wei-Tao; Fu, Qiang; Huang, Wen-Hai

2015-01-01

There is growing interest in biomaterials that can cure bone infection and also regenerate bone. In this study, two groups of implants composed of 10% (wt/wt) teicoplanin (TEC)-loaded borate bioactive glass (designated TBG) or calcium sulfate (TCS) were created and evaluated for their ability to release TEC in vitro and to cure methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis in a rabbit model. When immersed in phosphate-buffered saline (PBS), both groups of implants provided a sustained release of TEC at a therapeutic level for up to 3 to 4 weeks while they were gradually degraded and converted to hydroxyapatite. The TBG implants showed a longer duration of TEC release and better retention of strength as a function of immersion time in PBS. Infected rabbit tibiae were treated by debridement, followed by implantation of TBG or TCS pellets or intravenous injection with TEC, or were left untreated. Evaluation at 6 weeks postimplantation showed that the animals implanted with TBG or TCS pellets had significantly lower radiological and histological scores, lower rates of MRSA-positive cultures, and lower bacterial loads than those preoperatively and those of animals treated intravenously. The level of bone regeneration was also higher in the defects treated with the TBG pellets. The results showed that local TEC delivery was more effective than intravenous administration for the treatment of MRSA-induced osteomyelitis. Borate glass has the advantages of better mechanical strength, more desirable kinetics of release of TEC, and a higher osteogenic capacity and thus could be an effective alternative to calcium sulfate for local delivery of TEC. PMID:26416858

Comparison of Borate Bioactive Glass and Calcium Sulfate as Implants for the Local Delivery of Teicoplanin in the Treatment of Methicillin-Resistant Staphylococcus aureus-Induced Osteomyelitis in a Rabbit Model.

PubMed

Jia, Wei-Tao; Fu, Qiang; Huang, Wen-Hai; Zhang, Chang-Qing; Rahaman, Mohamed N

2015-12-01

There is growing interest in biomaterials that can cure bone infection and also regenerate bone. In this study, two groups of implants composed of 10% (wt/wt) teicoplanin (TEC)-loaded borate bioactive glass (designated TBG) or calcium sulfate (TCS) were created and evaluated for their ability to release TEC in vitro and to cure methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis in a rabbit model. When immersed in phosphate-buffered saline (PBS), both groups of implants provided a sustained release of TEC at a therapeutic level for up to 3 to 4 weeks while they were gradually degraded and converted to hydroxyapatite. The TBG implants showed a longer duration of TEC release and better retention of strength as a function of immersion time in PBS. Infected rabbit tibiae were treated by debridement, followed by implantation of TBG or TCS pellets or intravenous injection with TEC, or were left untreated. Evaluation at 6 weeks postimplantation showed that the animals implanted with TBG or TCS pellets had significantly lower radiological and histological scores, lower rates of MRSA-positive cultures, and lower bacterial loads than those preoperatively and those of animals treated intravenously. The level of bone regeneration was also higher in the defects treated with the TBG pellets. The results showed that local TEC delivery was more effective than intravenous administration for the treatment of MRSA-induced osteomyelitis. Borate glass has the advantages of better mechanical strength, more desirable kinetics of release of TEC, and a higher osteogenic capacity and thus could be an effective alternative to calcium sulfate for local delivery of TEC. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

[Polarized microscopic observation of the collagen change in bone healing during bone lengthening].

PubMed

Zou, Pei; Li, Junhui; Li, Zhuyi

2006-01-01

To investigate the feature and regularity of the collagen change in bone healing during bone lengthening. Bone lengthening model was made in the middle segment of the rabbit tibia. Five days after the model was established, the bone was lengthened 1.5 mm per day for 14 days. The rabbits were put to death after elongation, 7, 14, 21, 30, 40, 50, 60 and 70 days after elongation. The distracted area of the bone was imbedded with paraffin. After being stained by the picric acid-sirius red staining, the slice was observed under polarized microscope. The features of the collagen change in the distracted bone were as follows: (1) In the fibrous tissue of the distracted area during lengthening period and the early stage after lengthening, there was not only collagen III but also much collagen I. (2) Collagen I , II and III were observed in the cartilage. (3) Collagen I, II and III were also observed in the pseudo-growth plate. (4) Collagen I took the dominance during lengthening period and the late stage after lengthening. New bone formation in bone lengthening is under the distracted force, so the collagen changes have different features compared with that in fracture healing. Collagen I, II and III can be identified by picric acid-sirius red staining and polarized microscope, so a new method for studying the collagen typing in bone repairing is provided.

Antimicrobial and bone-forming activity of a copper coated implant in a rabbit model.

PubMed

Prinz, Cornelia; Elhensheri, Mohamed; Rychly, Joachim; Neumann, Hans-Georg

2017-08-01

Current strategies in implant technology are directed to generate bioactive implants that are capable to activate the regenerative potential of the surrounding tissue. On the other hand, implant-related infections are a common problem in orthopaedic trauma patients. To meet both challenges, i.e. to generate a bone implant with regenerative and antimicrobial characteristics, we tested the use of copper coated nails for surgical fixation in a rabbit model. Copper acetate was galvanically deposited with a copper load of 1 µg/mm 2 onto a porous oxide layer of Ti6Al4V nails, which were used for the fixation of a tibia fracture, inoculated with bacteria. After implantation of the nail the concentration of copper ions did not increase in blood which indicates that copper released from the implant was locally restricted to the fracture site. After four weeks, analyses of the extracted implants revealed a distinct antimicrobial effect of copper, because copper completely prevented both a weak adhesion and firm attachment of biofilm-forming bacteria on the titanium implant. To evaluate fracture healing, radiographic examination demonstrated an increased callus index in animals with copper coated nails. This result indicates a stimulated bone formation by releasing copper ions. We conclude that the use of implants with a defined load of copper ions enables both prevention of bacterial infection and the stimulation of regenerative processes.

A comparative 18F-FDG PET/CT imaging of experimental Staphylococcus aureus osteomyelitis and Staphylococcus epidermidis foreign-body-associated infection in the rabbit tibia

PubMed Central

2012-01-01

Background 18F-FDG-PET imaging has emerged as a promising method in the diagnosis of chronic osteomyelitis commonly due to Staphylococcus aureus. The inaccuracy of 18 F-FDG-PET in the detection of periprosthetic joint infections may be related to the predominance of low-virulent S. epidermidis strains as the causative pathogen. We have compared the18F-FDG-PET characteristics of S. aureus osteomyelitis and foreign-body-associated S. epidermidis infections under standardized laboratory conditions. Methods Twenty-two rabbits were randomized into three groups. In group 1, a localized osteomyelitis model induced with a clinical strain of S. aureus was applied. In groups 2 and 3, a foreign-body-associated infection model induced with a clinical or laboratory strain of S. epidermidis was applied. A small block of bone cement was surgically introduced into the medullary cavity of the proximal tibia followed by peri-implant injection of S. aureus (1 × 105 CFU/mL) or one of the two S. epidermidis (1 × 109 CFU/mL) strains with an adjunct injection of aqueous sodium morrhuate. In group 1, the cement block was surgically removed at 2 weeks but left in place in groups 2 and 3 in order to mimic foreign-body-associated S. epidermidis infections. At 8 weeks, the animals were imaged using 18 F-FDG PET/CT. The presence of bacterial infection was confirmed by cultures, and the severity of bone infections was graded by means of radiography, peripheral quantitative CT, and semi-quantitative histology. Results The S. aureus strain caused constantly culture-positive osteomyelitis. The clinical S. epidermidis strain resulted in foreign-body-associated infections, while the laboratory S. epidermidis strain (ATCC 35983) induced only occasionally culture-positive infections. There was a correlation (r = 0.645; P = 0.013) between semi-quantitative score of leukocyte infiltration and the 18 F-FDG uptake in animals with positive cultures. Standardized uptake value (SUV) of the infected bones was twofold (P < 0.001) in S. aureus animals compared with S. epidermidis animals, but there was only a trend (P = 0.053, ANOVA) in the differences of the corresponding SUV ratios. This was due to the altered 18 F-FDG uptake of the contralateral tibias probably reflecting a systemic impact of severe osteomyelitis. Conclusion The peri-implant inoculation of S. epidermidis, reflecting low virulence of the pathogen and limited leukocyte infiltration, was characterized by low 18 F-FDG uptake. PMID:22824200

Modified titanium implant as a gateway to the human body: the implant mediated drug delivery system.

PubMed

Park, Young-Seok; Cho, Joo-Youn; Lee, Shin-Jae; Hwang, Chee Il

2014-01-01

The aim of this study was to investigate the efficacy of a proposed new implant mediated drug delivery system (IMDDS) in rabbits. The drug delivery system is applied through a modified titanium implant that is configured to be implanted into bone. The implant is hollow and has multiple microholes that can continuously deliver therapeutic agents into the systematic body. To examine the efficacy and feasibility of the IMDDS, we investigated the pharmacokinetic behavior of dexamethasone in plasma after a single dose was delivered via the modified implant placed in the rabbit tibia. After measuring the plasma concentration, the areas under the curve showed that the IMDDS provided a sustained release for a relatively long period. The result suggests that the IMDDS can deliver a sustained release of certain drug components with a high bioavailability. Accordingly, the IMDDS may provide the basis for a novel approach to treating patients with chronic diseases.

Effect of step width manipulation on tibial stress during running.

PubMed

Meardon, Stacey A; Derrick, Timothy R

2014-08-22

Narrow step width has been linked to variables associated with tibial stress fracture. The purpose of this study was to evaluate the effect of step width on bone stresses using a standardized model of the tibia. 15 runners ran at their preferred 5k running velocity in three running conditions, preferred step width (PSW) and PSW±5% of leg length. 10 successful trials of force and 3-D motion data were collected. A combination of inverse dynamics, musculoskeletal modeling and beam theory was used to estimate stresses applied to the tibia using subject-specific anthropometrics and motion data. The tibia was modeled as a hollow ellipse. Multivariate analysis revealed that tibial stresses at the distal 1/3 of the tibia differed with step width manipulation (p=0.002). Compression on the posterior and medial aspect of the tibia was inversely related to step width such that as step width increased, compression on the surface of tibia decreased (linear trend p=0.036 and 0.003). Similarly, tension on the anterior surface of the tibia decreased as step width increased (linear trend p=0.029). Widening step width linearly reduced shear stress at all 4 sites (p<0.001 for all). The data from this study suggests that stresses experienced by the tibia during running were influenced by step width when using a standardized model of the tibia. Wider step widths were generally associated with reduced loading of the tibia and may benefit runners at risk of or experiencing stress injury at the tibia, especially if they present with a crossover running style. Copyright © 2014 Elsevier Ltd. All rights reserved.

Biomechanical evaluation of dental implants with three different designs: Removal torque and resonance frequency analysis in rabbits.

PubMed

Gehrke, Sergio Alexandre; Marin, Giovanni Wiel

2015-05-01

The objective of this study was to investigate the effect of implant design on stability and resistance to reverse torque in the tibia of rabbits. Three test groups were prepared using the different characteristics of each implant model: square threads with progressive depth to the apex, a cervical portion without threads and a self-tapping system that is quite pronounced and aggressive (Group 1); triangular threads with flat tips with increasing thread depth from the cervical portion to the apex and a small self-tapping portion with a short thread pitch (Group 2); long thread pitch, progressive thread depth, an apical area with a small self-tapping portion (Group 3). For the two last groups, a final single-use drill was provided for each implant. Nine rabbits received 54 conical implants with a same surface treatment. The resonance frequency was analysed four times (0, 6, 8 and 12 weeks), and removal torque values were measured at three time intervals after the implantations (6, 8 and 12 weeks). In comparing the implant stability quotient at the four time points, highly significant statistic differences were found (p = 1.29(-10)). The reverse torque at the three time points was also significantly different among the groups (p = 0.00015). The implants of Group 2, with seemingly less aggressive design, more quickly reached high values of stability and removal torque. Under the limitations of this study, however, it is possible that in cases in which there may be low osseointegration response, the implant design should be evaluated. Copyright © 2014 Elsevier GmbH. All rights reserved.

Chitosan scaffolds containing calcium phosphate salts and rhBMP-2: in vitro and in vivo testing for bone tissue regeneration.

PubMed

Guzmán, Rodrigo; Nardecchia, Stefania; Gutiérrez, María C; Ferrer, María Luisa; Ramos, Viviana; del Monte, Francisco; Abarrategi, Ander; López-Lacomba, José Luis

2014-01-01

Numerous strategies that are currently used to regenerate bone depend on employing biocompatible materials exhibiting a scaffold structure. These scaffolds can be manufactured containing particular active compounds, such as hydroxyapatite precursors and/or different growth factors to enhance bone regeneration process. Herein, we have immobilized calcium phosphate salts (CPS) and bone morphogenetic protein 2 (BMP-2)--combined or alone--into chitosan scaffolds using ISISA process. We have analyzed whether the immobilized bone morphogenetic protein preserved its osteoinductive capability after manufacturing process as well as BMP-2 in vitro release kinetic. We have also studied both the in vitro and in vivo biocompatibility of the resulting scaffolds using a rabbit model. Results indicated that rhBMP-2 remained active in the scaffolds after the manufacturing process and that its release kinetic was different depending on the presence of CPS. In vitro and in vivo findings showed that cells grew more in scaffolds with both CPS and rhBMP-2 and that these scaffolds induced more bone formation in rabbit tibia. Thus chitosan scaffolds containing both CPS and rhBMP-2 were more osteoinductive than their counterparts alone indicating that could be useful for bone regeneration purposes, such as some applications in dentistry.

Moderate tibia axial loading promotes discordant response of bone composition parameters and mechanical properties in a hindlimb unloading rat model.

PubMed

Yang, Peng-Fei; Huang, Ling-Wei; Nie, Xiao-Tong; Yang, Yue; Wang, Zhe; Ren, Li; Xu, Hui-Yun; Shang, Peng

2018-06-01

The purpose of the present study was to characterize the dynamic alterations of bone composition parameters and mechanical properties to disuse and mechanical intervention. A tail suspension hindlimb unloading model and an in vivo axial tibia loading model in rats were used. A moderate mechanical loading that was capable of engendering 800 µε tibia strain was applied to the right tibia of rats in both control and hindlimb unloading group across 28 days of the experimental period. The contralateral tibia served as control. Hindlimb unloading led to bone loss in tibia from day 14. Bone mineral density, mineral content and mechanical properties responded differently with microstructure to disuse in timing course. Mechanical loading of 800 µε tibia strain failed to alter the bone of the control group, but minimized the detrimental effects of unloading by completely prohibiting the decrease of bone mineral content and main mechanical properties after 28 days. Less obvious influence of mechanical loading on bone microstructure was found. The moderate mechanical loading is not able to stimulate the mechanical response of healthy tibia, but indeed lead to discordant recovery of bone composition parameters and mechanical properties.

Study of irradiated bone. III. Scintigraphic and radiographic detection of radiation-induced osteosarcomas. [/sup 99m/Tc-pyrophosphate; rabbits

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

King, M.A.; Casarett, G.W.; Weber, D.A.

1980-05-01

Within 1 yr after localized irradiation of a hind limb with single (1756 rads) or fractionated (4650 rads in 3 wk) x-ray doses, radiation-induced osteosarcomas were observed in four of nine single-dose rabbits and two of 11 fractionated-dose rabbits. Tumors were observed in the proximal tibia in five cases and the distal femur in one case. In terms of production of osteoid or osseous tissue, three tumors were well differentiated, one slightly differentiated, and two (spindle-cell tumors) undifferentiated. This report summarizes the Tc-99m pyrophosphate (TcPPi) imaging and autoradiographic, radiographic, and histologic studies of these osteosarcomas. The four differentiated osteosarcomas weremore » detected 1 to 2.5 mo earlier by TcPPi imaging than by radiography, whereas the two undifferentiated tumors were suspected 2 wk or 3.5 mo earlier radiographically. Autoradiograms showed TcPPi localization in bone produced by differentiated osteosarcomas, and in regions of reactive bone resorption and formation peripheral to tumors. The results support a recommendation for combined radiographic and scintigraphic techniques for the early detection of osteosarcomas.« less

Biodegradable nanocomposite coatings accelerate bone healing: In vivo evaluation

PubMed Central

Mehdikhani-Nahrkhalaji, Mehdi; Fathi, Mohammad Hossein; Mortazavi, Vajihesadat; Mousavi, Sayed Behrouz; Akhavan, Ali; Haghighat, Abbas; Hashemi-Beni, Batool; Razavi, Sayed Mohammad; Mashhadiabbas, Fatemeh

2015-01-01

Background: The aim of this study was to evaluate the interaction of bioactive and biodegradable poly (lactide-co-glycolide)/bioactive glass/hydroxyapatite (PBGHA) and poly (lactide-co-glycolide)/bioactive glass (PBG) nanocomposite coatings with bone. Materials and Methods: Sol-gel derived 58S bioactive glass nanoparticles, 50/50 wt% poly (lactic acid)/poly (glycolic acid) and hydroxyapatite nanoparticles were used to prepare the coatings. The nanocomposite coatings were characterized by scanning electron microscopy, X-ray diffraction and atomic force microscopy. Mechanical stability of the prepared nanocomposite coatings was studied during intramedullary implantation of coated Kirschner wires (K-wires) into rabbit tibia. Titanium mini-screws coated with nanocomposite coatings and without coating were implanted intramedullary in rabbit tibia. Bone tissue interaction with the prepared nanocomposite coatings was evaluated 30 and 60 days after surgery. The non-parametric paired Friedman and Kruskal-Wallis tests were used to compare the samples. For all tests, the level of significance was P < 0.05. Results: The results showed that nanocomposite coatings remained stable on the K-wires with a minimum of 96% of the original coating mass. Tissue around the coated implants showed no adverse reactions to the coatings. Woven and trabecular bone formation were observed around the coated samples with a minimum inflammatory reaction. PBG nanocomposite coating induced more rapid bone healing than PBGHA nanocomposite coating and titanium without coating (P < 0.05). Conclusion: It was concluded that PBG nanocomposite coating provides an ideal surface for bone formation and it could be used as a candidate for coating dental and orthopedic implants. PMID:25709681

Characteristics of contact and distance osteogenesis around modified implant surfaces in rabbit tibiae

PubMed Central

2017-01-01

Purpose Contact and distance osteogenesis occur around all endosseous dental implants. However, the mechanisms underlying these processes have not been fully elucidated. We hypothesized that these processes occur independently of each other. To test this, we used titanium (Ti) tubes to physically separate contact and distance osteogenesis, thus allowing contact osteogenesis to be measured in the absence of possible triggers from distance osteogenesis. Methods Sandblasted and acid-etched (SLA) and modified SLA (modSLA) implants were used. Both types had been sandblasted with large grit and then etched with acid. The modSLA implants then underwent additional treatment to increase hydrophilicity. The implants were implanted into rabbit tibiae, and half were implanted within Ti tubes. The bone-to-implant contact (BIC) ratio was calculated for each implant. Immunohistochemical analyses of bone morphogenetic protein (BMP)-2 expression and new bone formation (Masson trichrome stain) were performed. Results The implants outside of Ti tubes were associated with good bone formation along the implant surface. Implantation within a Ti tube significantly reduced the BIC ratio (P<0.001). Compared with the modSLA implants, the SLA implants were associated with significantly higher BIC ratios, regardless of the presence or absence of Ti tubes (P=0.043). In the absence of Ti tubes, the bone adjacent to the implant had areas of new bone formation that expressed BMP-2 at high levels. Conclusions This study disproved the null hypothesis and suggested that contact osteogenesis is initiated by signals from the old bone that undergoes distance osteogenesis after drilling. This signal may be BMP-2. PMID:28680714

Parametric analysis of occupant ankle and tibia injuries in frontal impact

PubMed Central

Mo, Fuhao; Jiang, Xiaoqing; Duan, Shuyong; Xiao, Zhi; Shi, Wei

2017-01-01

Objective Non-fatal tibia and ankle injuries without proper protection from the restraint system has gotten wide attention from researchers. This study aimed to investigate occupant tibia and ankle injuries under realistic frontal impact environment that is rarely considered in previous experimental and simulant studies. Methods An integrated occupant-vehicle model was established by coupling an isolated car cab model and a hybrid occupant model with a biofidelic pelvis-lower limb model, while its loading conditions were extracted from the realistic full-frontal impact test. A parametric study was implemented concerning instrument panel (IP) design and pedal intrusion/rotation parameters. Results The significant influences of the IP angle, pedal intrusion and pedal rotation on tibia axial force, tibia bending moment and ankle dorsiflexion angle are noted. By coupling their effects, a new evaluation index named CAIEI (Combined Ankle Injury Evaluation Index) is established to evaluate ankle injury (including tibia fractures in ankle region) risk and severity in robustness. Conclusions Overall results and analysis indicate that ankle dorsiflexion angle should be considered when judging the injury in lower limb under frontal impact. Meanwhile, the current index with coupling effects of tibia axial force, bending moment and ankle dorsiflexion angle is in a good correlation with the simulation injury outcomes. PMID:28910377

Polyaxial Screws in Locked Plating of Tibial Pilon Fractures.

PubMed

Yenna, Zachary C; Bhadra, Arup K; Ojike, Nwakile I; Burden, Robert L; Voor, Michael J; Roberts, Craig S

2015-08-01

This study examined the axial and torsional stiffness of polyaxial locked plating techniques compared with fixed-angle locked plating techniques in a distal tibia pilon fracture model. The effect of using a polyaxial screw to cross the fracture site was examined to determine its ability to control relative fracture site motion. A laboratory experiment was performed to investigate the biomechanical stiffness of distal tibia fracture models repaired with 3.5-mm anterior polyaxial distal tibial plates and locking screws. Sawbones Fourth Generation Composite Tibia models (Pacific Research Laboratories, Inc, Vashon, Washington) were used to model an Orthopaedic Trauma Association 43-A1.3 distal tibia pilon fracture. The polyaxial plates were inserted with 2 central locking screws at a position perpendicular to the cortical surface of the tibia and tested for load as a function of axial displacement and torque as a function of angular displacement. The 2 screws were withdrawn and inserted at an angle 15° from perpendicular, allowing them to span the fracture and insert into the opposing fracture surface. Each tibia was tested again for axial and torsional stiffness. In medial and posterior loading, no statistically significant difference was found between tibiae plated with the polyaxial plate and the central screws placed in the neutral position compared with the central screws placed at a 15° position. In torsional loading, a statistically significant difference was noted, showing greater stiffness in tibiae plated with the polyaxial plate and the central screws placed at a 15° position compared with tibiae plated with the central screws placed at a 0° (or perpendicular) position. This study showed that variable angle constructs show similar stiffness properties between perpendicular and 15° angle insertions in axial loading. The 15° angle construct shows greater stiffness in torsional loading. Copyright 2015, SLACK Incorporated.

Examining tissue composition, whole-bone morphology and mechanical behavior of GorabPrx1 mice tibiae: A mouse model of premature aging.

PubMed

Yang, Haisheng; Albiol, Laia; Chan, Wing-Lee; Wulsten, Dag; Seliger, Anne; Thelen, Michael; Thiele, Tobias; Spevak, Lyudmila; Boskey, Adele; Kornak, Uwe; Checa, Sara; Willie, Bettina M

2017-12-08

Gerodermia osteodysplastica (GO) is a segmental progeroid disorder caused by loss-of-function mutations in the GORAB gene, associated with early onset osteoporosis and bone fragility. A conditional mouse model of GO (Gorab Prx1 ) was generated in which the Gorab gene was deleted in long bones. We examined the biomechanical/functional relevance of the Gorab Prx1 mutants as a premature aging model by characterizing bone composition, tissue-level strains, and whole-bone morphology and mechanical properties of the tibia. MicroCT imaging showed that Gorab Prx1 tibiae had an increased anterior convex curvature and decreased cortical cross-sectional area, cortical thickness and moments of inertia, compared to littermate control (LC) tibiae. Fourier transform infrared (FTIR) imaging indicated a 34% decrease in mineral/matrix ratio and a 27% increase in acid phosphate content in the posterior metaphyseal cortex of the Gorab Prx1 tibiae (p < .05), suggesting delayed mineralization. In vivo strain gauge measurement and finite element analysis showed ∼two times higher tissue-level strains within the Gorab Prx1 tibiae relative to LC tibiae when subjected to axial compressive loads of the same magnitude. Three-point bending tests suggested that Gorab Prx1 tibiae were weaker and more brittle, as indicated by decreasing whole-bone strength (46%), stiffness (55%), work-to-fracture (61%) and post-yield displacement (47%). Many of these morphological and biomechanical characteristics of the Gorab Prx1 tibia recapitulated changes in other animal models of skeletal aging. Future studies are necessary to confirm how our observations might guide the way to a better understanding and treatment of GO. Copyright © 2017 Elsevier Ltd. All rights reserved.

Derivation and application of a mathematical model for long bone growth.

PubMed

Seetharam, Suneil; Bhatia, Sujata K

2012-01-01

The objective of this work was to develop a mathematical model of long bone growth and to gain insights regarding growth disorders. A cell balance (mass balance of moving cells) assessment was performed on the three regions of the growth plate, to determine the variables (including number of proliferating cells, and division rate of proliferating cells) that influence tibia growth rate. Once this relationship was established, clinical data were used to understand how tibia growth rate and number of proliferating cells change with time. These equations were then inserted into the model to determine how cell division rate changes with time. The model was utilized to determine the influence of growth time, and to measure changes in vitamin C deficiency, Indian hedgehog (IHH) expression, and bone morphogenetic protein-2 (BMP-2) implants on tibia length. According to the model, a 10-month discrepancy in growth time between the two tibias is required to produce clinically significant leg asymmetry. In addition, vitamin C deficiency, IHH overexpression, and BMP-2 implants can all affect tibia length. These bioactive molecules have the greatest effect on tibia growth rate when these perturbations occur early in life for extended periods of time. The results are significant for modeling and predicting the effects of perturbations, including bioactive implants, on long bone growth.

Tricalcium phosphate-Fluorapatite as bone tissue engineering: Evaluation of bioactivity and biocompatibility.

PubMed

Taktak, Rym; Elghazel, Achwek; Bouaziz, Jamel; Charfi, Slim; Keskes, Hassib

2018-05-01

Biocomposites consisting of β Tricalcium phosphate (β-TCP) with 26.52% Fluorapatite (Fap) were elaborated and characterized in order to evaluate it potential application in bone graft substitute. Bioactivity was determined with in vitro tests by immersion of samples in simulated fluid body for several periods of times. The SEM, EDS and Atomic Absorption Spectroscopy showed the deposition of apatite layer on the surface of samples showing a good bioactivity. However, after 6days of soaking, the dissolution rate of Ca 2+ and PO 4 3- decreased which due probably to the improvement of crystallization of the apatite layer. These findings agree with those observed after 6weeks postimplantation of prepared macroporous scaffolds in rabbits. All histological observations of the preliminary in vivo study in the tibia of rabbits proved the biocompatibility and the resorption of the investigated bioceramic. In contrast, the implantation period will have to be optimized by further extensive animal experiments. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of pore size on bone ingrowth into porous titanium implants fabricated by additive manufacturing: An in vivo experiment.

PubMed

Taniguchi, Naoya; Fujibayashi, Shunsuke; Takemoto, Mitsuru; Sasaki, Kiyoyuki; Otsuki, Bungo; Nakamura, Takashi; Matsushita, Tomiharu; Kokubo, Tadashi; Matsuda, Shuichi

2016-02-01

Selective laser melting (SLM) is an additive manufacturing technique with the ability to produce metallic scaffolds with accurately controlled pore size, porosity, and interconnectivity for orthopedic applications. However, the optimal pore structure of porous titanium manufactured by SLM remains unclear. In this study, we evaluated the effect of pore size with constant porosity on in vivo bone ingrowth in rabbits into porous titanium implants manufactured by SLM. Three porous titanium implants (with an intended porosity of 65% and pore sizes of 300, 600, and 900μm, designated the P300, P600, and P900 implants, respectively) were manufactured by SLM. A diamond lattice was adapted as the basic structure. Their porous structures were evaluated and verified using microfocus X-ray computed tomography. Their bone-implant fixation ability was evaluated by their implantation as porous-surfaced titanium plates into the cortical bone of the rabbit tibia. Bone ingrowth was evaluated by their implantation as cylindrical porous titanium implants into the cancellous bone of the rabbit femur for 2, 4, and 8weeks. The average pore sizes of the P300, P600, and P900 implants were 309, 632, and 956μm, respectively. The P600 implant demonstrated a significantly higher fixation ability at 2weeks than the other implants. After 4weeks, all models had sufficiently high fixation ability in a detaching test. Bone ingrowth into the P300 implant was lower than into the other implants at 4weeks. Because of its appropriate mechanical strength, high fixation ability, and rapid bone ingrowth, our results indicate that the pore structure of the P600 implant is a suitable porous structure for orthopedic implants manufactured by SLM. Copyright © 2015 Elsevier B.V. All rights reserved.

Treatment of osteomyelitis and repair of bone defect by degradable bioactive borate glass releasing vancomycin.

PubMed

Xie, Zongping; Liu, Xin; Jia, Weitao; Zhang, Changqing; Huang, Wenhai; Wang, Jianqiang

2009-10-15

The effectiveness of a degradable and bioactive borate glass has been compared with the clinically used calcium sulfate in the treatment of osteomyelitis of rabbits, as a carrier for vancomycin. The bone infections were induced in the tibias of 65 rabbits by injecting methicillin-resistant Staphylococcus aureus (MRSA). After 3 weeks, these rabbits were distributed into 4 groups and treated by debridement. Pure borate glass (BG), vancomycin-loaded calcium sulfate (VCS) and vancomycin-loaded borate glass (VBG) were implanted into the infection sites of groups 2 to 4 respectively. After 8 weeks, the effectiveness of treatment was assessed radiographically, bacteriologically, and histopathologically. The results showed that the negative rates of MRSA examination for rabbits were 36.36%, 18.18%, 73.33% and 81.25% respectively for groups 1 to 4. Significant differences were observed radiographically, bacteriologically, and histopathologically between groups 1 and 4, groups 2 and 3, and between groups 2 and 4. The best result of treatment was observed in group 4. Radiographically, VBG was found to be mostly reabsorbed and replaced by lots of new bones, whereas, VCS was completely reabsorbed and replaced by modest new bones. Histopathologically, there were lots of newly formed bones around VBG without any foreign body response, and only modest new bones around VCS with obvious foreign body response. VBG proved to have excellent biocompatibility and to be very effective in eradicating osteomyelitis and simultaneously stimulating bone regeneration, avoiding the disadvantages of VCS.

Nanostructures and hydrophilicity influence osseointegration: a biomechanical study in the rabbit tibia.

PubMed

Wennerberg, Ann; Jimbo, Ryo; Stübinger, Stefan; Obrecht, Marcel; Dard, Michel; Berner, Simon

2014-09-01

Implant surface properties have long been identified as an important factor to promote osseointegration. The importance of nanostructures and hydrophilicity has recently been discussed. The aim of this study was to investigate how nanostructures and wettability influence osseointegration and to identify whether the wettability, the nanostructure or both in combination play the key role in improved osseointegration. Twenty-six adult rabbits each received two Ti grade 4 discs in each tibia. Four different types of surface modifications with different wettability and nanostructures were prepared: hydrophobic without nanostructures (SLA), with nanostructures (SLAnano); hydrophilic with two different nanostructure densities (low density: pmodSLA, high density: SLActive). All four groups were intended to have similar chemistry and microroughness. The surfaces were evaluated with contact angle measurements, X-ray photoelectron spectroscopy, scanning electron microscopy, atomic force microscopy and interferometry. After 4 and 8 weeks healing time, pull-out tests were performed. SLA and SLAnano were hydrophobic, whereas SLActive and pmodSLA were super-hydrophilic. No nanostructures were present on the SLA surface, but the three other surface modifications clearly showed the presence of nanostructures, although more sparsely distributed on pmodSLA. The hydrophobic samples showed higher carbon contamination levels compared with the hydrophilic samples. After 4 weeks healing time, SLActive implants showed the highest pull-out values, with significantly higher pull-out force than SLA and SLAnano. After 8 weeks, the SLActive implants had the highest pull-out force, significantly higher than SLAnano and SLA. The strongest bone response was achieved with a combination of wettability and the presence of nanostructures (SLActive). © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Autologous implantation of BMP2-expressing dermal fibroblasts to improve bone mineral density and architecture in rabbit long bones.

PubMed

Ishihara, Akikazu; Weisbrode, Steve E; Bertone, Alicia L

2015-10-01

Cell-mediated gene therapy may treat bone fragility disorders. Dermal fibroblasts (DFb) may be an alternative cell source to stem cells for orthopedic gene therapy because of their rapid cell yield and excellent plasticity with bone morphogenetic protein-2 (BMP2) gene transduction. Autologous DFb or BMP2-expressing autologous DFb were administered in twelve rabbits by two delivery routes; a transcortical intra-medullar infusion into tibiae and delayed intra-osseous injection into femoral drill defects. Both delivery methods of DFb-BMP2 resulted in a successful cell engraftment, increased bone volume, bone mineral density, improved trabecular bone microarchitecture, greater bone defect filling, external callus formation, and trabecular surface area, compared to non-transduced DFb or no cells. Cell engraftment within trabecular bone and bone marrow tissue was most efficiently achieved by intra-osseous injection of DFb-BMP2. Our results suggested that BMP2-expressing autologous DFb have enhanced efficiency of engraftment in target bones resulting in a measurable biologic response by the bone of improved bone mineral density and bone microarchitecture. These results support that autologous implantation of DFb-BMP2 warrants further study on animal models of bone fragility disorders, such as osteogenesis imperfecta and osteoporosis to potentially enhance bone quality, particularly along with other gene modification of these diseases. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Progress in Finite Element Modeling of the Lower Extremities

DTIC Science & Technology

2015-06-01

bending and subsequent injury , e.g., the distal tibia motion results in bending of the tibia rather than the tibia rotating about the knee joint...layers, rich anisotropy, and wide variability. Developing a model for predictive injury capability, therefore, needs to be versatile and flexible to... injury capability presents many challenges, the first of which is identifying the types of conditions where injury prediction is needed. Our focus

Injury tolerance of tibia for the car-pedestrian impact.

PubMed

Mo, Fuhao; Arnoux, Pierre Jean; Jure, Jean Jaques; Masson, Catherine

2012-05-01

Lower limbs are normally the first contacted body region during car-pedestrian accidents, and easily suffer serious injuries. The previous tibia bending tolerances for pedestrian safety were mainly developed from three-point bending tests on tibia mid-shaft. The tibia tolerances of other locations are still not investigated enough. In addition, tibia loading condition under the car-pedestrian impact should be explored to compare with the three-point bending. This work aims to investigate the injury tolerance of tibia fracture with combined experimental data and numerical simulation. Eleven new reported quasi-static bending tests of tibia mid-shaft, and additional eleven dynamic mid-shaft bending test results in the previous literature were used to define injury risk functions. Furthermore, to investigate the influence of tibia locations on bending tolerance, finite element simulations with lower limb model were implemented according to three-point bending and pedestrian impact conditions. The regressive curve of tibia bending tolerance was obtained from the simulations on the different impact locations, and indicated that tibia fracture tolerance could vary largely due to the impact locations for the car-pedestrian crash. Copyright © 2011 Elsevier Ltd. All rights reserved.

Combination of Heel-strike like Mechanical Loading with Deproteinized Cancellous Bone Scaffold Implantation to Repair Segmental Bone Defects in Rabbits.

PubMed

Huang, Guofeng; Liu, Guojun; Zhang, Feng; Gao, Jianting; Wang, Jiangze; Chen, Qi; Wu, Benwen; Ding, Zhenqi; Cai, Taoyi

2017-01-01

Under physiological conditions bone defects often occur at mechanical load bearing sites and bone substitutes used for regeneration should be similarly subjected to mechanical loading stress. In this study, we investigated whether a novel heel-strike like mechanical loading method can be used as a complementary therapy to promote bone regeneration following bone substitute grafting. To test this, three groups of rabbits with segmental bone defects in the tibia were implanted with bovine deproteinized cancellous bone scaffold (DCBS), with one group also receiving heel-strike like mechanical loading generated by a rap stress stimulator. From weeks 4-12 post-operation X-ray and micro-CT scanning showed that rabbits receiving combination therapy had significantly more callus at the bone defect. Moreover, bone defects in the combination group were completely replaced with new bone at week 12, while the DCBS implantation alone group healed only partially and rabbits receiving neither DCBS nor mechanical loading developed only small calluses throughout the observation period. Analysis of micro-CT scanning results demonstrated that new bone density in the combination group was significantly higher than the DCBS only group at weeks 4 and 12 ( p <0.05). H&E staining results also indicated a significantly higher percentage of new bone in the bone defect area and a lower percentage of residual scaffold in the combination group compared to the DCBS only group ( p <0.05). Thus, this heel-strike like mechanical loading method appears to accelerate bone regeneration following substitute implantation by restoring a local mechanical loading environment in segmental bone defects.

Bone Augmentation in Rabbit Tibia Using Microfixed Cobalt-Chromium Membranes with Whole Blood and Platelet-Rich Plasma.

PubMed

Decco, Oscar A; Beltrán, Víctor; Zuchuat, Jésica I; Cura, Andrea C; Lezcano, María F; Engelke, Wilfried

2015-07-30

Bone augmentation is a subject of intensive investigation in regenerative bone medicine and constitutes a clinical situation in which autogenous bone grafts or synthetic materials are used to aid new bone formation. Based on a non-critical defect, Co-Cr barrier membranes were placed on six adult Fauve de Bourgogne rabbits, divided into two groups: whole blood and PRP. Three densitometric controls were performed during the experiment. The animals were euthanized at 30, 45, 60, and 110 days. The presence of newly formed bone was observed. Samples for histological studies were taken from the augmentation center. External and internal bone tissue augmentation was observed in almost all cases. Significant differences between PRP- and whole blood-stimulated bone augmentation were not observed. At 60 days, bones with PRP presented higher angiogenesis, which may indicate more proliferation and cellular activity. PRP activates the bone regeneration process under optimized conditions by stimulation of osteoblast proliferation after six weeks, when a significant difference in cellular activity was observed. Membranes could stimulate bone augmentation at the site of placement and in the surrounding areas.

Evaluation of early bone response to fluoride-modified and anodically oxidized titanium implants through continuous removal torque analysis.

PubMed

Kwon, Taek-Ka; Lee, Hyo-Jung; Min, Seung-Ki; Yeo, In-Sung

2012-10-01

To compare between a bioactive and a bioinert implant with different geometries by continuous measurement of the removal torque and calculation of the angular momentum of each surfaced implant. Six New Zealand white rabbits were used in the study. Each rabbit received 2 implants. A bioactive fluoride-modified implant with a conical connection and microthread design was inserted into one tibia, and a bioinert anodically oxidized implant with an external connection design was inserted into the other. After 2 weeks of implant insertion, the removal torque values were continuously measured according to time. Using the time-torque curve resulting from the measurements, the maximum values were determined, and the angular momenta were calculated. The anodically oxidized implant had significantly higher peak removal torque and angular momentum values than the fluoride-modified implant (P < 0.05). The impact of the fluoride-modified bioactive implant on early bone response remains unclear. Considering the angular momentum of dental implants may assist in the elucidation of the effect of implant geometry on bone response.

The selective cathepsin K inhibitor MIV-711 attenuates joint pathology in experimental animal models of osteoarthritis.

PubMed

Lindström, Erik; Rizoska, Biljana; Tunblad, Karin; Edenius, Charlotte; Bendele, Alison M; Maul, Don; Larson, Michael; Shah, Neha; Yoder Otto, Valerie; Jerome, Chris; Grabowska, Urszula

2018-03-09

MIV-711 is a highly potent and selective cathepsin K inhibitor. The current article summarizes the therapeutic effects of MIV-711 on joint pathology in rabbits subjected to anterior cruciate ligament transection (ACLT), and the prophylactic effects on joint pathology in dogs subjected to partial medial meniscectomy, two surgical models of osteoarthritis (OA). Starting 1 week after surgery, rabbits were dosed daily via oral gavage with either MIV-711 or vehicle (n = 7/group) for 7 weeks. The four treatment groups were: (1) sham + vehicle; (2) ACLT + vehicle; (3) ACLT + MIV-711, 30 µmol/kg and (4) ACLT + MIV-711, 100 µmol/kg. Subchondral bone and articular cartilage structures were assessed by µCT, histomorphometry, and scoring. Dogs subjected to partial medial meniscectomy received either MIV-711 (30 µmol/kg) or vehicle (n = 15/group) via oral gavage once daily, starting 1 day before meniscectomy, for 28 days. Cartilage degradation was assessed at the macroscopic and microscopic levels. The exposures of MIV-711 were assessed in both studies and biomarkers reflecting bone resorption (HP-1 in rabbits, CTX-I in dogs) and cartilage degradation (CTX-II) were measured. In ACLT rabbits, MIV-711 decreased HP-1 levels by up to 72% (p < 0.001) and CTX-II levels by up to 74% (p < 0.001) compared to ACLT vehicle controls. ACLT surgery significantly reduced the total thickness of the subchondral bone plate and reduced trabecular bone volume in the femur and tibia. These effects were reversed by MIV-711. ACLT resulted in cartilage thickening, which was attenuated by MIV-711. MIV-711 did not affect osteophyte formation or Mankin scores. In dogs, MIV-711 reduced CTX-I and CTX-II levels by 86% (p < 0.001) and 80% (p < 0.001), respectively. Synovial CTX-II levels were reduced by 55-57% (p < 0.001) compared to baseline. MIV-711-treated animals had 25-37% lower macroscopic scores in the femur condyles and 13-33% lower macroscopic scores in the tibial plateaus. MIV-711 prevents subchondral bone loss and partially attenuates cartilage pathology in two animal models of OA. These beneficial effects of MIV-711 on joint pathology are observed in conjunction with decreases in bone and cartilage biomarkers that have been shown to be clinically attainable in human. The data support the further development of MIV-711 for the treatment of OA.

A biomechanical model for actively controlled snow ski bindings.

PubMed

Hull, M L; Ramming, J E

1980-11-01

Active control of snow ski bindings is a new design concept which potentially offers improved protection from lower extremity injury. Implementation of this concept entails measuring physical variables and calculating loading and/or deformation in injury prone musculoskeletal components. The subject of this paper is definition of a biomechanical model for calculating tibia torsion based on measurements of torsion loading between the boot and ski. Previous control schemes have used leg displacement only to indicate tibia torsion. The contributions of both inertial and velocity-dependent torques to tibia loading are explored and it is shown that both these moments must be included in addition to displacement-dependent moments. A new analog controller design which includes inertia, damping, and stiffness terms in the tibia load calculation is also presented.

Acceleration of tendon-bone healing of anterior cruciate ligament graft using intermittent negative pressure in rabbits.

PubMed

Sun, Zhengming; Wang, Xiaoqing; Ling, Ming; Wang, Wei; Chang, Yanhai; Yang, Guang; Dong, Xianghui; Wu, Shixun; Wu, Xueyuan; Yang, Bo; Chen, Ming

2017-04-18

The purpose of this study was to test effects of negative pressure on tendon-bone healing after reconstruction of anterior cruciate ligament (ACL) in rabbits. Hind legs of 24 New Zealand White rabbits were randomly selected as negative pressure group and the contralateral hind legs as control. Reconstruction of the ACL was done. Joints of the negative pressure side were placed with drainage tubes connecting the micro-negative pressure aspirator. Control side was placed with ordinary drainage tubes. Drainage tubes on both sides were removed at the same time 5 days after operation. After 6 weeks, joint fluid was drawn to detect the expression levels of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α); at the same time, femur-ligament-tibia complex was obtained to determine tendon graft tension and to observe the histomorphology, blood vessels of the tendon-bone interface, and expression of vascular endothelial growth factor (VEGF). The maximum load breakage of tendon graft was significantly greater in the negative pressure group than in the control group (P < 0.05). Histological studies of the tendon-bone interface found that there was more new bone formation containing chondroid cells and aligned connective tissue in the negative pressure group than in the control group. Expression of VEGF was higher in the negative pressure group than in the control group (P < 0.01). Content of IL-1β and TNF-α in synovial fluid is lower in the negative pressure group than in the control group (P < 0.01). Intermittent negative pressure plays an active role in tendon-bone healing and creeping substitution of ACL reconstruction in the rabbits.

Effect of low-magnitude different-frequency whole-body vibration on subchondral trabecular bone microarchitecture, cartilage degradation, bone/cartilage turnover, and joint pain in rabbits with knee osteoarthritis.

PubMed

Junbo, Wang; Sijia, Liu; Hongying, Chen; Lei, Liu; Pu, Wang

2017-06-15

Whole-body vibration(WBV) has been suggested for the prevention of subchondral bone loss of knee osteoarthritis (OA) . This study examined the effects of different frequency of whole-body vibration on subchondral trabecular bone microarchitecture, cartilage degradation and metabolism of the tibia and femoral condyle bone, and joint pain in an anterior cruciate ligament transection (ACLT)-induced knee osteoarthritisrabbit model. Ninety adult rabbits were divided into six groups: all groups received unilateral ACLT; Group 1, ACLT only; Group 2, 5 Hz WBV; Group 3, 10 Hz WBV; Group 4, 20 Hz WBV; Group 5, 30 Hz WBV; and Group 6, 40 Hz WBV. Pain was tested via weight-bearing asymmetry. Subchondral trabecular bone microarchitecture was examined using in vivo micro-computed tomography. Knee joint cartilage was evaluated by gross morphology, histology, and ECM gene expression level (aggrecan and type II collagen [CTX-II]). Serum bone-specific alkaline phosphatase, N-mid OC, cartilage oligometric protein, CPII, type I collagen, PIIANP, G1/G2 aggrecan levels, and urinary CTX-II were analyzed. After 8 weeks of low-magnitude WBV, the lower frequency (10 Hz and 20 Hz) WBV treatment decreased joint pain and cartilage resorption, accelerated cartilage formation, delayed cartilage degradation especially at the 20 Hz regimen. However, the higher frequencies (30 Hz and 40 Hz) had worse effects, with worse limb function and cartilage volume as well as higher histological scores and cartilage resorption. In contrast, both prevented loss of trabeculae and increased bone turnover. No significant change was observed in the 5 Hz WBV group. Our data demonstrate that the lower frequencies (10 Hz and 20 Hz) of low-magnitude WBV increased bone turnover, delayed cartilage degeneration, and caused a significant functional change of the OA-affected limb in ACLT-induced OA rabbit model but did not reverse OA progression after 8 weeks of treatment.

Differences in crestal bone-to-implant contact following an under-drilling compared to an over-drilling protocol. A study in the rabbit tibia.

PubMed

Cohen, Omer; Ormianer, Zeev; Tal, Haim; Rothamel, Daniel; Weinreb, Miron; Moses, Ofer

2016-12-01

The objective of this study is to compare bone-to-implant contact (BIC) between implants inserted at high torque due to under-drilling of the crestal bone to those inserted at low torque due to over-drilling of the crestal bone. Forty implants with diameters of 3.75 mm (group A) or 3.55 mm (group B) were inserted in the proximal tibiae of NZW rabbits in two separate surgeries on day 0 or 21. Osteotomy of the crestal bone was finalized with a 3.65-mm drill. In group A, implants were inserted at torque ≥35 Ncm (under-drilling) and in group B with torque <10 Ncm (over-drilling). Implants and their surrounding bone were retrieved on day 42, thus creating 3- and 6-week observation periods, processed for non-decalcified histology and stained with toluidine blue. Crestal BIC (c-BIC) and total BIC (t-BIC) were measured. Wilcoxon test was used to evaluate differences between groups. Three weeks post-surgery, the mean c-BIC in group A was 16.3 ± 3.3 vs 31.5 ± 3.4 % in group B (P < 0.05). At 6 weeks, a similar trend was observed (group A: 28.7 ± 3.6 %; group B: 38.4 ± 4.9 %) (P > 0.05). No differences in t-BIC were noted at 3 weeks and at 6 weeks between the groups. Insertion of implants with an over-drilling protocol of the crestal aspect of the osteotomy resulted in increased short-term crestal bone-to-implant contact. Insertion of implants with a high torque following an under-drilling protocol, commonly used for immediate loading, may reduce crestal bone-to-implant contact at early healing stages.

Time course of epiphyseal growth plate fusion in rat tibiae

NASA Technical Reports Server (NTRS)

Martin, E. A.; Ritman, E. L.; Turner, R. T.

2003-01-01

Although the rat is the most common animal model used in studying osteoporosis, it is often used inappropriately. Osteoporosis is a disease that most commonly occurs in humans long after growth plate fusion with the associated cessation of longitudinal bone growth, but there has been a question as to when or to what extent the rat growth plate fuses. To investigate this question, we used microcomputed X-ray tomography, at voxel resolutions ranging from (5.7 micro m)(3) to (11 micro m)(3), to image the proximal epiphyseal growth plates of both male (n = 19) and female (n = 15) rat tibiae, ranging in age from 2 to 25 months. The three-dimensional images were used to evaluate fusion of the epiphyseal growth plate by quantitating the amount of cancellous bone that has bridged across the growth plate. The results suggest that the time course of fusion of the epiphyseal growth plate follows a sigmoidal pattern, with 10% of the maximum number of bridges having formed by 3.9 months in the male tibiae and 5.8 months in the female tibiae, 50% of the maximum number of bridges having formed by 5.6 months in the male tibiae and 5.9 months in the female tibiae, and 90% of the total maximum of bridges have formed by 7.4 months for the males and 6.5 months for the females. The total volume of bridges per tibia at the age at which the maximum number of bridges per tibia has first formed is 0.99 mm(3)/tibia for the males and 0.40 mm(3)/tibia for the females. After the maximum number of bridges (-290 for females, -360 for males) have formed the total volume of bridges per tibia continues to increase for an additional 7.0 months in the males and 17.0 months for the females until they reach maximum values (-1.5 mm(3)/tibia for the males and -2.2 mm(3)/tibia for the females).

The Improved Biological Performance of a Novel Low Elastic Modulus Implant

PubMed Central

Lei, Wei; Wang, Zhen; Li, Jing; Fan, Xiangli; Li, Xiaokang; Li, Shujun; Guo, Zheng

2013-01-01

Background The mismatch of the elastic modulus between implants and bone tissue can lead to stress shielding, bone resorption and poor osseointegration. Compared with normal bone tissue, this problem is much more serious in osteoporosis. The purpose of this study was designed to find out whether the novel Ti-24Nb-4Zr-7.9Sn (TNZS) implant with low elastic modulus and high strength was suitable for biomedical material, especially in osteoporosis. Methodology In vitro study, the viability and Alkaline phosphatase (ALP) activity of osteoblasts on the TNZS and Ti-6V-4V (TAV) were observed. In vivo study, 30 adult female New Zealand rabbits were selected and divided randomly into two groups: sham-operation (SHAM, n = 6) and ovariectomised in combination with methylprednisolone treatment (OVX+MP, n = 24). Two implants were then placed in the tibia of each OVX + MP group rabbit, one in each side (left: TAV; right: TNZS). The OVX + MP group rabbits were sacrificed at 4 and 12 weeks after the implantation. The osteoporotic bone responses to the TNZS and TAV implants were evaluated by pull-out test, Micro-CT analyses and histological observation. Principal Findings Compared with the TAV group, the TNZS group showed a significant increase (P<0.05) in cell viability and ALP activity, new bone formation and pull-out force. Conclusions The novel TNZS implants show good biological performance both in vitro and in vivo, which suggests that the alloys are suitable for biomedical applications, especially in osteoporosis. PMID:23437048

Repair of Segmental Load-Bearing Bone Defect by Autologous Mesenchymal Stem Cells and Plasma-Derived Fibrin Impregnated Ceramic Block Results in Early Recovery of Limb Function

PubMed Central

Ng, Min Hwei; Duski, Suryasmi; Tan, Kok Keong; Yusof, Mohd Reusmaazran; Low, Kiat Cheong; Mohamed Rose, Isa; Mohamed, Zahiah; Bin Saim, Aminuddin; Idrus, Ruszymah Bt Hj

2014-01-01

Calcium phosphate-based bone substitutes have not been used to repair load-bearing bone defects due to their weak mechanical property. In this study, we reevaluated the functional outcomes of combining ceramic block with osteogenic-induced mesenchymal stem cells and platelet-rich plasma (TEB) to repair critical-sized segmental tibial defect. Comparisons were made with fresh marrow-impregnated ceramic block (MIC) and partially demineralized allogeneic bone block (ALLO). Six New Zealand White female rabbits were used in each study group and three rabbits with no implants were used as negative controls. By Day 90, 4/6 rabbits in TEB group and 2/6 in ALLO and MIC groups resumed normal gait pattern. Union was achieved significantly faster in TEB group with a radiological score of 4.50 ± 0.78 versus ALLO (1.06 ± 0.32), MIC (1.28 ± 0.24), and negative controls (0). Histologically, TEB group scored the highest percentage of new bone (82% ± 5.1%) compared to ALLO (5% ± 2.5%) and MIC (26% ± 5.2%). Biomechanically, TEB-treated tibiae achieved the highest compressive strength (43.50 ± 12.72 MPa) compared to those treated with ALLO (15.15 ± 3.57 MPa) and MIC (23.28 ± 6.14 MPa). In conclusion, TEB can repair critical-sized segmental load-bearing bone defects and restore limb function. PMID:25165699

Examination of a biodegradable magnesium screw for the reconstruction of the anterior cruciate ligament: A pilot in vivo study in rabbits.

PubMed

Diekmann, Julia; Bauer, Sylvie; Weizbauer, Andreas; Willbold, Elmar; Windhagen, Henning; Helmecke, Patrick; Lucas, Arne; Reifenrath, Janin; Nolte, Ingo; Ezechieli, Marco

2016-02-01

The reconstruction of the anterior cruciate ligament is, for the most part, currently performed with interference screws made of titanium or degradable polymers. The aim of this study was to investigate the use of biodegradable magnesium interference screws for such a procedure because of their known biocompatibility and reported osteoconductive effects. The left tibiae of each of 18 rabbits were implanted with a magnesium-based (MgYREZr-alloy) screw, and another 18 with a titanium-based control. Each group was divided into observation periods of 4, 12 and 24weeks. After sacrifice, μCT scans were acquired to assess the amount of the gas liberated and the degradation rate of the implant. Histological evaluations were performed to investigate the local tissue response adjacent to the implant and to assess the status of the attachment between the tendon and the bone tissue. The μCT scans showed that liberation of gas was most prominent 4weeks after implantation and was significantly decreased by 24weeks. All screws remained in situ and formed a sufficient connection with the tendon and sufficient osseous integration at 24weeks. Histological evaluations showed neither inflammatory reactions nor necrosis of the tendon. The results of this pilot study in rabbits indicate that this magnesium-based interference screw should be considered as an alternative to conventional implant materials. Copyright © 2015 Elsevier B.V. All rights reserved.

Simulation on the internal structure of three-dimensional proximal tibia under different mechanical environments.

PubMed

Fang, Juan; Gong, He; Kong, Lingyan; Zhu, Dong

2013-12-20

Bone can adjust its morphological structure to adapt to the changes of mechanical environment, i.e. the bone structure change is related to mechanical loading. This implies that osteoarthritis may be closely associated with knee joint deformity. The purposes of this paper were to simulate the internal bone mineral density (BMD) change in three-dimensional (3D) proximal tibia under different mechanical environments, as well as to explore the relationship between mechanical environment and bone morphological abnormity. The right proximal tibia was scanned with CT to reconstruct a 3D proximal tibia model in MIMICS, then it was imported to finite element software ANSYS to establish 3D finite element model. The internal structure of 3D proximal tibia of young normal people was simulated using quantitative bone remodeling theory in combination with finite element method, then based on the changing pattern of joint contact force on the tibial plateau in valgus knees, the mechanical loading was changed, and the simulated normal tibia structure was used as initial structure to simulate the internal structure of 3D proximal tibia for old people with 6° valgus deformity. Four regions of interest (ROIs) were selected in the proximal tibia to quantitatively analyze BMD and compare with the clinical measurements. The simulation results showed that the BMD distribution in 3D proximal tibia was consistent with clinical measurements in normal knees and that in valgus knees was consistent with the measurement of patients with osteoarthritis in clinics. It is shown that the change of mechanical environment is the main cause for the change of subchondral bone structure, and being under abnormal mechanical environment for a long time may lead to osteoarthritis. Besides, the simulation method adopted in this paper can more accurately simulate the internal structure of 3D proximal tibia under different mechanical environments. It helps to better understand the mechanism of osteoarthritis and provides theoretical basis and computational method for the prevention and treatment of osteoarthritis. It can also serve as basis for further study on periprosthetic BMD changes after total knee arthroplasty, and provide a theoretical basis for optimization design of prosthesis.

Simulation on the internal structure of three-dimensional proximal tibia under different mechanical environments

PubMed Central

2013-01-01

Background Bone can adjust its morphological structure to adapt to the changes of mechanical environment, i.e. the bone structure change is related to mechanical loading. This implies that osteoarthritis may be closely associated with knee joint deformity. The purposes of this paper were to simulate the internal bone mineral density (BMD) change in three-dimensional (3D) proximal tibia under different mechanical environments, as well as to explore the relationship between mechanical environment and bone morphological abnormity. Methods The right proximal tibia was scanned with CT to reconstruct a 3D proximal tibia model in MIMICS, then it was imported to finite element software ANSYS to establish 3D finite element model. The internal structure of 3D proximal tibia of young normal people was simulated using quantitative bone remodeling theory in combination with finite element method, then based on the changing pattern of joint contact force on the tibial plateau in valgus knees, the mechanical loading was changed, and the simulated normal tibia structure was used as initial structure to simulate the internal structure of 3D proximal tibia for old people with 6° valgus deformity. Four regions of interest (ROIs) were selected in the proximal tibia to quantitatively analyze BMD and compare with the clinical measurements. Results The simulation results showed that the BMD distribution in 3D proximal tibia was consistent with clinical measurements in normal knees and that in valgus knees was consistent with the measurement of patients with osteoarthritis in clinics. Conclusions It is shown that the change of mechanical environment is the main cause for the change of subchondral bone structure, and being under abnormal mechanical environment for a long time may lead to osteoarthritis. Besides, the simulation method adopted in this paper can more accurately simulate the internal structure of 3D proximal tibia under different mechanical environments. It helps to better understand the mechanism of osteoarthritis and provides theoretical basis and computational method for the prevention and treatment of osteoarthritis. It can also serve as basis for further study on periprosthetic BMD changes after total knee arthroplasty, and provide a theoretical basis for optimization design of prosthesis. PMID:24359345

Bone Augmentation in Rabbit Tibia Using Microfixed Cobalt-Chromium Membranes with Whole Blood and Platelet-Rich Plasma

PubMed Central

Decco, Oscar A.; Beltrán, Víctor; Zuchuat, Jésica I.; Cura, Andrea C.; Lezcano, María F.; Engelke, Wilfried

2015-01-01

Background: Bone augmentation is a subject of intensive investigation in regenerative bone medicine and constitutes a clinical situation in which autogenous bone grafts or synthetic materials are used to aid new bone formation. Method: Based on a non-critical defect, Co-Cr barrier membranes were placed on six adult Fauve de Bourgogne rabbits, divided into two groups: whole blood and PRP. Three densitometric controls were performed during the experiment. The animals were euthanized at 30, 45, 60, and 110 days. The presence of newly formed bone was observed. Samples for histological studies were taken from the augmentation center. Results: External and internal bone tissue augmentation was observed in almost all cases. Significant differences between PRP- and whole blood–stimulated bone augmentation were not observed. At 60 days, bones with PRP presented higher angiogenesis, which may indicate more proliferation and cellular activity. Conclusion: PRP activates the bone regeneration process under optimized conditions by stimulation of osteoblast proliferation after six weeks, when a significant difference in cellular activity was observed. Membranes could stimulate bone augmentation at the site of placement and in the surrounding areas. PMID:28793476

Effect of surface anodization on stability of orthodontic microimplant

PubMed Central

Karmarker, Sanket; Yu, Wonjae

2012-01-01

Objective To determine the effect of surface anodization on the interfacial strength between an orthodontic microimplant (MI) and the rabbit tibial bone, particularly in the initial phase after placement. Methods A total of 36 MIs were driven into the tibias of 3 mature rabbits by using the self-drilling method and then removed after 6 weeks. Half the MIs were as-machined (n = 18; machined group), while the remaining had anodized surfaces (n = 18; anodized group). The peak insertion torque (PIT) and the peak removal torque (PRT) values were measured for the 2 groups of MIs. These values were then used to calculate the interfacial shear strength between the MI and cortical bone. Results There were no statistical differences in terms of PIT between the 2 groups. However, mean PRT was significantly greater for the anodized implants (3.79 ± 1.39 Ncm) than for the machined ones (2.05 ± 1.07 Ncm) (p < 0.01). The interfacial strengths, converted from PRT, were calculated at 10.6 MPa and 5.74 MPa for the anodized and machined group implants, respectively. Conclusions Anodization of orthodontic MIs may enhance their early-phase retention capability, thereby ensuring a more reliable source of absolute anchorage. PMID:23112925

Influence of Screw Length and Bone Thickness on the Stability of Temporary Implants

PubMed Central

Fernandes, Daniel Jogaib; Elias, Carlos Nelson; Ruellas, Antônio Carlos de Oliveira

2015-01-01

The purpose of this work was to study the influence of screw length and bone thickness on the stability of temporary implants. A total of 96 self-drilling temporary screws with two different lengths were inserted into polyurethane blocks (n = 66), bovine femurs (n = 18) and rabbit tibia (n = 12) with different cortical thicknesses (1 to 8 mm). Screws insertion in polyurethane blocks was assisted by a universal testing machine, torque peaks were collected by a digital torquemeter and bone thickness was monitored by micro-CT. The results showed that the insertion torque was significantly increased with the thickness of cortical bone from polyurethane (p < 0.0001), bovine (p = 0.0035) and rabbit (p < 0.05) sources. Cancellous bone improved significantly the mechanical implant stability. Insertion torque and insertion strength was successfully moduled by equations, based on the cortical/cancellous bone behavior. Based on the results, insertion torque and bone strength can be estimate in order to prevent failure of the cortical layer during temporary screw placement. The stability provided by a cortical thickness of 2 or 1 mm coupled to cancellous bone was deemed sufficient for temporary implants stability. PMID:28793582

Osseoconductivity of a Specific Streptavidin-Biotin-Fibronectin Surface Coating of Biotinylated Titanium Implants - A Rabbit Animal Study.

PubMed

Kämmerer, Peer W; Lehnert, Michael; Al-Nawas, Bilal; Kumar, Vinay V; Hagmann, Sebastien; Alshihri, Abdulmonem; Frerich, Bernhard; Veith, Michael

2015-10-01

Biofunctionalized implant surfaces may accelerate bony integration and increase long-term stability. The aim of the study was to evaluate the osseous reaction toward biomimetic titanium implants surfaces coated with quasicovalent immobilized fibronectin in an in vivo animal model. A total of 84 implants (uncoated [control 1, n = 36], streptavidin-biotin coated [test 1, n = 24], streptavidin-biotin-fibronectin coated [test 2, n = 24]) were inserted 1 mm supracortically in the proximal tibia of 12 rabbits. The samples were examined after 3 and 6 weeks. Total bone-implant contact (tBIC; %), bone-implant contact in the cortical (cBIC; %) and in the spongious bone (sBIC; %) as well as the percentage of linear bone fill (PLF; %) were evaluated. After 3 weeks, streptavidin-biotin-fibronectin implants had a significant higher sBIC (p = .043) and PLF (p = .007) compared with the uncoated samples. After 6 weeks, this difference was significant for tBIC (p = .016) and cBIC (p < .001). Additionally, uncoated screws showed a significant higher sBIC when compared with the fibronectin coating (p < .001). Streptavidin-biotin-coated implants showed less bone growth at both time points of all examined parameters when compared with their counterparts (all p < .001). Quasicovalent immobilization of biotinylated fibronectin with the streptavidin-biotin-fibronectin system on smooth surface titanium shows a beneficial faster osseous healing in vivo. Besides, an antifouling effect of the streptavidin-biotin coating was proven. © 2015 Wiley Periodicals, Inc.

A New Measurement Technique of the Characteristics of Nutrient Artery Canals in Tibias Using Materialise's Interactive Medical Image Control System Software

PubMed Central

Li, Jiantao; Zhang, Hao; Yin, Peng; Su, Xiuyun; Zhao, Zhe; Zhou, Jianfeng; Li, Chen; Li, Zhirui; Zhang, Lihai; Tang, Peifu

2015-01-01

We established a novel measurement technique to evaluate the anatomic information of nutrient artery canals using Mimics (Materialise's Interactive Medical Image Control System) software, which will provide full knowledge of nutrient artery canals to assist in the diagnosis of longitudinal fractures of tibia and choosing an optimal therapy. Here we collected Digital Imaging and Communications in Medicine (DICOM) format of 199 patients hospitalized in our hospital. All three-dimensional models of tibia in Mimics were reconstructed. In 3-matic software, we marked five points in tibia which located at intercondylar eminence, tibia tuberosity, outer ostium, inner ostium, and bottom of medial malleolus. We then recorded Z-coordinates values of the five points and performed statistical analysis. Our results indicate that foramen was found to be absent in 9 (2.3%) tibias, and 379 (95.2%) tibias had single nutrient foramen. The double foramina was observed in 10 (2.5%) tibias. The mean of tibia length was 358 ± 22 mm. The mean foraminal index was 31.8%  ± 3%. The mean distance between tibial tuberosity and foramen (TFD) is 66 ± 12 mm. Foraminal index has significant positive correlation with TFD (r = 0.721, P < 0.01). Length of nutrient artery canals has significant negative correlation with TFD (r = −0.340, P < 0.01) and has significant negative correlation with foraminal index (r = −0.541, P < 0.01). PMID:26788498

Stem cell therapy for enhancement of bone consolidation in distraction osteogenesis

PubMed Central

Yang, Y.; Lin, S.; Wang, B.; Gu, W.

2017-01-01

Objectives Distraction osteogenesis (DO) mobilises bone regenerative potential and avoids the complications of other treatments such as bone graft. The major disadvantage of DO is the length of time required for bone consolidation. Mesenchymal stem cells (MSCs) have been used to promote bone formation with some good results. Methods We hereby review the published literature on the use of MSCs in promoting bone consolidation during DO. Results Studies differed in animal type (mice, rabbit, dog, sheep), bone type (femur, tibia, skull), DO protocols and cell transplantation methods. Conclusion The majority of studies reported that the transplantation of MSCs enhanced bone consolidation or formation in DO. Many questions relating to animal model, DO protocol and cell transplantation regime remain to be further investigated. Clinical trials are needed to test and confirm these findings from animal studies. Cite this article: Y. Yang, S. Lin, B. Wang, W. Gu, G. Li. Stem cell therapy for enhancement of bone consolidation in distraction osteogenesis: A contemporary review of experimental studies. Bone Joint Res 2017;6:385–390. DOI: 10.1302/2046-3758.66.BJR-2017-0023. PMID:28634158

In Vivo Axial Loading of the Mouse Tibia

PubMed Central

Melville, Katherine M.; Robling, Alexander G.

2015-01-01

Summary Non-invasive methods to apply controlled, cyclic loads to the living skeleton are used as an anabolic agent to stimulate new bone formation in adults and enhance bone mass accrual in growing animals. These methods are also invaluable for understanding bone signaling pathways. Our focus here is on a particular loading model: in vivo axial compression of the mouse tibia. An advantage of loading the tibia is that changes are present in both the cancellous envelope of the proximal tibia and the cortical bone of the tibial diaphysis. To load the tibia of the mouse axially in vivo, a cyclic compressive load is applied up to five times a week to a single tibia per mouse for a duration lasting from 1 day to 6 weeks. With the contralateral limb as an internal control, the anabolic response of the skeleton to mechanical stimuli can be studied in a pairwise experimental design. Here, we describe the key parameters that must be considered before beginning an in vivo mouse tibial loading experiment, including methods for in vivo strain gauging of the tibial midshaft, and then we describe general methods for loading the mouse tibia for an experiment lasting multiple days. PMID:25331046

Geometry reconstruction method for patient-specific finite element models for the assessment of tibia fracture risk in osteogenesis imperfecta.

PubMed

Caouette, Christiane; Ikin, Nicole; Villemure, Isabelle; Arnoux, Pierre-Jean; Rauch, Frank; Aubin, Carl-Éric

2017-04-01

Lower limb deformation in children with osteogenesis imperfecta (OI) impairs ambulation and may lead to fracture. Corrective surgery is based on empirical assessment criteria. The objective was to develop a reconstruction method of the tibia for OI patients that could be used as input of a comprehensive finite element model to assess fracture risks. Data were obtained from three children with OI and tibia deformities. Four pQCT scans were registered to biplanar radiographs, and a template mesh was deformed to fit the bone outline. Cortical bone thickness was computed. Sensitivity of the model to missing slices of pQCT was assessed by calculating maximal von Mises stress for a vertical hopping load case. Sensitivity of the model to ±5 % of cortical thickness measurements was assessed by calculating loads at fracture. Difference between the mesh contour and bone outline on the radiographs was below 1 mm. Removal of one pQCT slice increased maximal von Mises stress by up to 10 %. Simulated ±5 % variation of cortical bone thickness leads to variations of up to 4.1 % on predicted fracture loads. Using clinically available tibia imaging from children with OI, the developed reconstruction method allowed the building of patient-specific finite element models.

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

Using Patient Demographics and Statistical Modeling to Predict Knee Tibia Component Sizing in Total Knee Arthroplasty.

PubMed

Ren, Anna N; Neher, Robert E; Bell, Tyler; Grimm, James

2018-06-01

Preoperative planning is important to achieve successful implantation in primary total knee arthroplasty (TKA). However, traditional TKA templating techniques are not accurate enough to predict the component size to a very close range. With the goal of developing a general predictive statistical model using patient demographic information, ordinal logistic regression was applied to build a proportional odds model to predict the tibia component size. The study retrospectively collected the data of 1992 primary Persona Knee System TKA procedures. Of them, 199 procedures were randomly selected as testing data and the rest of the data were randomly partitioned between model training data and model evaluation data with a ratio of 7:3. Different models were trained and evaluated on the training and validation data sets after data exploration. The final model had patient gender, age, weight, and height as independent variables and predicted the tibia size within 1 size difference 96% of the time on the validation data, 94% of the time on the testing data, and 92% on a prospective cadaver data set. The study results indicated the statistical model built by ordinal logistic regression can increase the accuracy of tibia sizing information for Persona Knee preoperative templating. This research shows statistical modeling may be used with radiographs to dramatically enhance the templating accuracy, efficiency, and quality. In general, this methodology can be applied to other TKA products when the data are applicable. Copyright © 2018 Elsevier Inc. All rights reserved.

Foam-reinforced elderly human tibia approximates young human tibia better than porcine tibia: a study of the structural properties of three soft tissue fixation devices.

PubMed

Bailey, Shana B; Grover, Dustin M; Howell, Stephen M; Hull, Maury L

2004-01-01

Because there is an insufficient supply of young human knees, an alternative is needed for evaluating anterior cruciate ligament reconstructions. The authors determined whether an elderly human tibia reinforced with foam is a better substitute for a young human tibia than a porcine tibia in this study of the tibialfixation of a soft tissue anterior cruciate ligament graft using 3 devices. A foam-reinforced elderly human tibia more closely approximates the performance of a young human tibia than porcine tibia. Biomechanical study. Failure mode, stiffness, yield, and slippage were determined for a double-looped tendon graft fixed with either an interference screw, WasherLoc, or tandem washers in young human tibiae, foam-reinforced tibiae from elderly humans, and porcine tibiae. The stiffness and yield of interference screw and WasherLoc fixation in foam-reinforced tibiae more closely approximate those in young human tibiae than in porcine tibiae. Slippage of all combinations of tibiae and fixation devices was similar A foam-reinforced human tibia more closely approximates the performance of a young human tibia than that of porcine tibia in this study. Fixation devices should be tested in foam-reinforced tibiae from elderly humans rather than tibiae from large farm animals when the supply of young human knees is insufficient.

Freezing of Rat Tibiae at -20°C Does Not Affect the Mechanical Properties of Intramedullary Bone/Implant-Interface: Brief Report

PubMed Central

Diefenbeck, Michael; Mückley, Thomas; Zankovych, Sergiy; Bossert, Jörg; Jandt, Klaus D; Schrader, Christian; Schmidt, Jürgen; Finger, Ulrich; Faucon, Mathilde

2011-01-01

Background: The effects of freezing-thawing cycles on intramedullary bone-implant interfaces have been studied in a rat model in mechanical pull-out tests. Implants: Twenty TiAl6V4 rods (Ø 0.8 mm, length 10 mm) implanted in rat tibiae Methods: 10 rats underwent bilateral tibial implantation of titanium rods. At eight weeks, the animals were sacrificed and tibiae harvested for biomechanical testing. Eight tibiae were frozen and stored at -20°C for 14 days, the remaining eight were evaluated immediately post-harvest. Pull-out tests were used to determine maximum force and interfacial shear strength. Results: There were no significant differences between fresh and those of the frozen-thawed group in maximum force or in interfacial shear strength. Conclusion: Frozen Storage of rat tibiae containing implants at -20° C has no effects on the biomechanical properties of Bone/ Implant interface. PMID:21760868

Changes in geometrical and biomechanical properties of immature male and female rat tibia

NASA Technical Reports Server (NTRS)

Zernicke, Ronald F.; Hou, Jack C.-H.; Vailas, Arthur C.; Nishimoto, Mitchell; Patel, Sanjay

1990-01-01

The differences in the geometry and mechanical properties of immature male and female rat tibiae were detailed in order to provide comparative data for spaceflight, exercise, or disease experiments that use immature rats as an animal model. The experiment focuses on the particularly rapid period of growth that occurs in the Sprague-Dawley rat between 40 and 60 d of age. Tibial length and middiaphysical cross-sectional data were analyzed for eight different groups of rats according to age and sex, and tibial mechanical properties were obtained via three-point bending tests to failure. Results indicate that, during the 15 d period of rapid growth, changes in rat tibial geometry are more important than changes in bone material properties for influencing the mechanical properties of the tibia. Male tibiae changed primarily in structural properties, while in the female rats major changes in mechanical properties of the tibia were only attributable to changes in the structural properties of the bone.

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

Proceedings of the 2010 AFMS Medical Research Symposium. Volume 3. Enroute Track: Abstracts and Presentations

DTIC Science & Technology

2011-03-15

comparison of proximal tibia, proximal humerus and distal femur infusion rates under high pressure using the EZ-IO Intraosseous device on an adult...contaminated complex musculoskeletal wounds. METHODS: We adapted a previously characterized caprine model. Under anesthesia , complex musculoskeletal...of proximal tibia, proximal humerus and distal femur infusion rates under high pressure using the EZ-IO Intraosseous device on an adult swine model

A Novel Injectable Borate Bioactive Glass Cement as an Antibiotic Delivery Vehicle for Treating Osteomyelitis

PubMed Central

Cui, Xu; Gu, Yi-Fei; Jia, Wei-Tao; Rahaman, Mohamed N.; Wang, Yang; Huang, Wen-Hai; Zhang, Chang-Qing

2014-01-01

Background A novel injectable cement composed of chitosan-bonded borate bioactive glass (BG) particles was evaluated as a carrier for local delivery of vancomycin in the treatment of osteomyelitis in a rabbit tibial model. Materials and Methods The setting time, injectability, and compressive strength of the borate BG cement, and the release profile of vancomycin from the cement were measured in vitro. The capacity of the vancomycin-loaded BG cement to eradicate methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis in rabbit tibiae in vivo was evaluated and compared with that for a vancomycin-loaded calcium sulfate (CS) cement and for intravenous injection of vancomycin. Results The BG cement had an injectability of >90% during the first 3 minutes after mixing, hardened within 30 minutes and, after hardening, had a compressive strength of 18±2 MPa. Vancomycin was released from the BG cement into phosphate-buffered saline for up to 36 days, and the cumulative amount of vancomycin released was 86% of the amount initially loaded into the cement. In comparison, vancomycin was released from the CS cement for up 28 days and the cumulative amount released was 89%. Two months post-surgery, radiography and microbiological tests showed that the BG and CS cements had a better ability to eradicate osteomyelitis when compared to intravenous injection of vancomycin, but there was no significant difference between the BG and CS cements in eradicating the infection. Histological examination showed that the BG cement was biocompatible and had a good capacity for regenerating bone in the tibial defects. Conclusions These results indicate that borate BG cement is a promising material both as an injectable carrier for vancomycin in the eradication of osteomyelitis and as an osteoconductive matrix to regenerate bone after the infection is cured. PMID:24427311

A novel injectable borate bioactive glass cement as an antibiotic delivery vehicle for treating osteomyelitis.

PubMed

Ding, Hao; Zhao, Cun-Ju; Cui, Xu; Gu, Yi-Fei; Jia, Wei-Tao; Rahaman, Mohamed N; Wang, Yang; Huang, Wen-Hai; Zhang, Chang-Qing

2014-01-01

A novel injectable cement composed of chitosan-bonded borate bioactive glass (BG) particles was evaluated as a carrier for local delivery of vancomycin in the treatment of osteomyelitis in a rabbit tibial model. The setting time, injectability, and compressive strength of the borate BG cement, and the release profile of vancomycin from the cement were measured in vitro. The capacity of the vancomycin-loaded BG cement to eradicate methicillin-resistant Staphylococcus aureus (MRSA)-induced osteomyelitis in rabbit tibiae in vivo was evaluated and compared with that for a vancomycin-loaded calcium sulfate (CS) cement and for intravenous injection of vancomycin. The BG cement had an injectability of >90% during the first 3 minutes after mixing, hardened within 30 minutes and, after hardening, had a compressive strength of 18 ± 2 MPa. Vancomycin was released from the BG cement into phosphate-buffered saline for up to 36 days, and the cumulative amount of vancomycin released was 86% of the amount initially loaded into the cement. In comparison, vancomycin was released from the CS cement for up 28 days and the cumulative amount released was 89%. Two months post-surgery, radiography and microbiological tests showed that the BG and CS cements had a better ability to eradicate osteomyelitis when compared to intravenous injection of vancomycin, but there was no significant difference between the BG and CS cements in eradicating the infection. Histological examination showed that the BG cement was biocompatible and had a good capacity for regenerating bone in the tibial defects. These results indicate that borate BG cement is a promising material both as an injectable carrier for vancomycin in the eradication of osteomyelitis and as an osteoconductive matrix to regenerate bone after the infection is cured.

Bone stress in runners with tibial stress fracture.

PubMed

Meardon, Stacey A; Willson, John D; Gries, Samantha R; Kernozek, Thomas W; Derrick, Timothy R

2015-11-01

Combinations of smaller bone geometry and greater applied loads may contribute to tibial stress fracture. We examined tibial bone stress, accounting for geometry and applied loads, in runners with stress fracture. 23 runners with a history of tibial stress fracture & 23 matched controls ran over a force platform while 3-D kinematic and kinetic data were collected. An elliptical model of the distal 1/3 tibia cross section was used to estimate stress at 4 locations (anterior, posterior, medial and lateral). Inner and outer radii for the model were obtained from 2 planar x-ray images. Bone stress differences were assessed using two-factor ANOVA (α=0.05). Key contributors to observed stress differences between groups were examined using stepwise regression. Runners with tibial stress fracture experienced greater anterior tension and posterior compression at the distal tibia. Location, but not group, differences in shear stress were observed. Stepwise regression revealed that anterior-posterior outer diameter of the tibia and the sagittal plane bending moment explained >80% of the variance in anterior and posterior bone stress. Runners with tibial stress fracture displayed greater stress anteriorly and posteriorly at the distal tibia. Elevated tibial stress was associated with smaller bone geometry and greater bending moments about the medial-lateral axis of the tibia. Future research needs to identify key running mechanics associated with the sagittal plane bending moment at the distal tibia as well as to identify ways to improve bone geometry in runners in order to better guide preventative and rehabilitative efforts. Copyright © 2015 Elsevier Ltd. All rights reserved.

Validation of multiple subject-specific finite element models of unicompartmental knee replacement.

PubMed

Tuncer, Mahmut; Cobb, Justin P; Hansen, Ulrich N; Amis, Andrew A

2013-10-01

Accurate computer modelling of the fixation of unicompartmental knee replacements (UKRs) is a valuable design tool. However, models must be validated with in vitro mechanical tests to have confidence in the results. Ten fresh-frozen cadaveric knees with differing bone densities were CT-scanned to obtain geometry and bone density data, then implanted with cementless medial Oxford UKRs by an orthopaedic surgeon. Five strain gauge rosettes were attached to the tibia and femur of each knee and the bone constructs were mechanically tested. They were re-tested following implanting the cemented versions of the implants. Finite element models of four UKR tibiae and femora were developed. Sensitivity assessments and convergence studies were conducted to optimise modelling parameters. The cemented UKR pooled R(2) values for predicted versus measured bone strains were 0.85 and 0.92 for the tibia and femur respectively. The cementless UKR pooled R(2) values were slightly lower at 0.62 and 0.73 which may have been due to the irregularity of bone resections. The correlation of the results was attributed partly to the improved material property prediction method used in this project. This study is the first to validate multiple UKR tibiae and femora for bone strain across a range of specimen bone densities. Copyright © 2013 IPEM. Published by Elsevier Ltd. All rights reserved.

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.

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

Models of tibial fracture healing in normal and Nf1-deficient mice.

PubMed

Schindeler, Aaron; Morse, Alyson; Harry, Lorraine; Godfrey, Craig; Mikulec, Kathy; McDonald, Michelle; Gasser, Jürg A; Little, David G

2008-08-01

Delayed union and nonunion are common complications associated with tibial fractures, particularly in the distal tibia. Existing mouse tibial fracture models are typically closed and middiaphyseal, and thus poorly recapitulate the prevailing conditions following surgery on a human open distal tibial fracture. This report describes our development of two open tibial fracture models in the mouse, where the bone is broken either in the tibial midshaft (mid-diaphysis) or in the distal tibia. Fractures in the distal tibial model showed delayed repair compared to fractures in the tibial midshaft. These tibial fracture models were applied to both wild-type and Nf1-deficient (Nf1+/-) mice. Bone repair has been reported to be exceptionally problematic in human NF1 patients, and these patients can also spontaneously develop tibial nonunions (known as congenital pseudarthrosis of the tibia), which are recalcitrant to even vigorous intervention. pQCT analysis confirmed no fundamental differences in cortical or cancellous bone in Nf1-deficient mouse tibiae compared to wild-type mice. Although no difference in bone healing was seen in the tibial midshaft fracture model, the healing of distal tibial fractures was found to be impaired in Nf1+/- mice. The histological features associated with nonunited Nf1+/- fractures were variable, but included delayed cartilage removal, disproportionate fibrous invasion, insufficient new bone anabolism, and excessive catabolism. These findings imply that the pathology of tibial pseudarthrosis in human NF1 is complex and likely to be multifactorial.

Revascularization of diaphyseal bone segments by vascular bundle implantation.

PubMed

Nagi, O N

2005-11-01

Vascularized bone transfer is an effective, established treatment for avascular necrosis and atrophic or infected nonunions. However, limited donor sites and technical difficulty limit its application. Vascular bundle transplantation may provide an alternative. However, even if vascular ingrowth is presumed to occur in such situations, its extent in aiding revascularization for ultimate graft incorporation is not well understood. A rabbit tibia model was used to study and compare vascularized, segmental, diaphyseal, nonvascularized conventional, and vascular bundle-implanted grafts with a combination of angiographic, radiographic, histopathologic, and bone scanning techniques. Complete graft incorporation in conventional grafts was observed at 6 months, whereas it was 8 to 12 weeks with either of the vascularized grafts. The pattern of radionuclide uptake and the duration of graft incorporation between vascular segmental bone grafts (with intact endosteal blood supply) and vascular bundle-implanted segmental grafts were similar. A vascular bundle implanted in the recipient bone was found to anastomose extensively with the intraosseous circulation at 6 weeks. Effective revascularization of bone could be seen when a simple vascular bundle was introduced into a segment of bone deprived of its normal blood supply. This simple technique offers promise for improvement of bone graft survival in clinical circumstances.

The Anteroposterior Axis of the Proximal Tibia Can Change After Tibial Resection in Total Knee Arthroplasty: Computer Simulation Using Asian Osteoarthritis Knees.

PubMed

Ushio, Tetsuro; Mizu-Uchi, Hideki; Okazaki, Ken; Ma, Yuan; Kuwashima, Umito; Iwamoto, Yukihide

2017-03-01

We evaluated the effect of cutting surface on the anteroposterior (AP) axis of the proximal tibia using a 3-dimensional (3D) bone model to ensure proper tibial rotational alignment in total knee arthroplasty. 3D bone models were reconstructed from the preoperative computed tomography data of 93 Japanese osteoarthritis knees with varus deformity. The AP axis was defined as the perpendicular bisector of the medial and lateral condylar centers in a 3D coordinate system. Bone cutting of the proximal tibia was performed with various tibial posterior slopes (0°, 3°, 7°) to the mechanical axis, and we compared the AP axes before and after bone cutting. The AP axis before bone cutting crossed a point at about 16% (one-sixth) of the distance from the medial edge of the patellar tendon at its tibial attachment. The AP axis after bone cutting was significantly internally rotated at all posterior slopes: 4.1° at slope 0°, 3.0° at slope 3°, and 2.1° at slope 7°. The percentages of cases with differences of more than 3° or 5° were 66.7% and 34.4% at slope 0°, 53.8% and 24.7% at slope 3°, and 38.3% and 11.8% at slope 7°, respectively. The AP axis of the proximal tibia may be rotated internally after resection of the proximal tibia in total knee arthroplasty. Hence, surgeons should recognize the effect of changes in the cutting surface on rotational alignment of the proximal tibia. Copyright © 2016 Elsevier Inc. All rights reserved.

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 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.

Three dimensional finite element analysis of the influence of posterior tibial slope on the anterior cruciate ligament and knee joint forward stability.

PubMed

Qi, Yong; Sun, Hongtao; Fan, Yueguang; Li, Feimeng; Wang, Yunting; Ge, Chana

2018-03-23

To explore the biomechanical influence of posterior tibial angle on the anterior cruciate ligament and knee joint forward stability. The left knee joint of a healthy volunteer was scanned by CT and MRI. The data were imported into Mimics software to obtain 3D models of bone, cartilage, meniscus and ligament structures, and then Geomagic software was used to modify of the image. The relative displacement between tibia and femur and the stress of ACL were recorded. ACL tension was 12.195 N in model with 2∘ PTS, 12.639 N in model with 7∘ PTS, 18.658 N in model with 12∘ PTS. the relative displacement of the tibia and femur was 2.735 mm in model with 2∘ PTS, 3.086 mm in model with 7∘ PTS, 3.881 mm in model with 12∘ PTS. In the model with 30∘ flexion, the maximum tension of ACL was 24.585 N in model with 2∘ PTS, 25.612 N in model with 7∘ PTS, 31.481 N in model with 12∘ PTS. The relative displacement of the tibia and femur was 5.590 mm in model with 2∘ PTS, 6.721 mm in model with 7∘ PTS, 6.952 mm in model with 12∘ PTS. In the 90∘ flexion models, ACL tension was 5.119 N in model with 2∘ PTS, 8.674 N in model with 7∘ PTS, 9.314 N in model with 12∘ PTS. The relative displacement of the tibia and femur was 0.276 mm in model with 2∘ PTS, 0.577 mm in model with 7∘ PTS, 0.602 mm in model with 12∘ PTS. The steeper PTS may be a risk factor in ACL injury.

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.

Can the contralateral limb be used as a control during the growing period in a rodent model?

PubMed

Mustafy, Tanvir; Londono, Irène; Villemure, Isabelle

2018-05-12

The contralateral limb is often used as a control in various clinical, forensic and anthropological studies. However, no studies have been performed to determine if the contra-lateral limb is a suitable control during the bone development period. The aim of this study was to determine the bilateral symmetry of growing rat tibiae in terms of geometric shape, mechanical strength and bone morphological parameters with developmental stages. Left and right tibias of 18 male Sprague-Dawley rats at 4, 8 and 12 weeks of age were scanned with micro-CT for bone-morphometric evaluation and for 3D deviation analysis to quantify the geometric shape variations between left and right tibiae. Overall tibial lengths and curvatures were also measured, and bone mechanical strength was investigated using three-point bending tests. Deviation distributions between bilateral tibiae remained below 0.5 mm for more than 80% of the geometry for all groups. Tibial lengths, longitudinal tibial curvatures, bone-morphometric parameters and mechanical strengths changed significantly during the growing period but kept a strong degree of symmetry between bilateral tibiae. These results suggest that bilateral tibiae can be considered symmetrical in nature and that contralateral limb can be used as a control during the growing period in different experimental scenarios. Copyright © 2018 Elsevier Ltd. All rights reserved.

Numerical simulations of human tibia osteosynthesis using modular plates based on Nitinol staples.

PubMed

Tarniţă, Daniela; Tarniţă, D N; Popa, D; Grecu, D; Tarniţă, Roxana; Niculescu, D; Cismaru, F

2010-01-01

The shape memory alloys exhibit a number of remarkable properties, which open new possibilities in engineering and more specifically in biomedical engineering. The most important alloy used in biomedical applications is NiTi. This alloy combines the characteristics of the shape memory effect and superelasticity with excellent corrosion resistance, wear characteristics, mechanical properties and a good biocompatibility. These properties make it an ideal biological engineering material, especially in orthopedic surgery and orthodontics. In this work, modular plates for the osteosynthesis of the long bones fractures are presented. The proposed modular plates are realized from identical modules, completely interchangeable, made of titanium or stainless steel having as connecting elements U-shaped staples made of Nitinol. Using computed tomography (CT) images to provide three-dimensional geometric details and SolidWorks software package, the three dimensional virtual models of the tibia bone and of the modular plates are obtained. The finite element models of the tibia bone and of the modular plate are generated. For numerical simulation, VisualNastran software is used. Finally, displacements diagram, von Misses strain diagram, for the modular plate and for the fractured tibia and modular plate ensemble are obtained.

PIXE microbeam analysis of the metallic debris release around endosseous implants

NASA Astrophysics Data System (ADS)

Buso, G. P.; Galassini, S.; Moschini, G.; Passi, P.; Zadro, A.; Uzunov, N. M.; Doyle, B. L.; Rossi, P.; Provencio, P.

2005-10-01

The mechanical friction that occurs during the surgical insertion of endosseous implants, both in dentistry and orthopaedics, may cause the detachment of metal debris which are dislodged into the peri-implant tissues and can lead to adverse clinical effects. This phenomenon more likely happens with coated or roughened implants that are the most widely employed. In the present study were studied dental implants screws made of commercially pure titanium and coated using titanium plasma-spray (TPS) technique. The implants were inserted in the tibia of rabbits, and removed "en bloc" with the surrounding bone after one month. After proper processing and mounting on plastic holders, samples from bones were analysed by EDXRF setup at of National Laboratories of Legnaro, INFN, Italy, and consequently at 3 MeV proton microbeam setup at Sandia National Laboratories. Elemental maps were drawn, showing some occasional presence of metal particles in the peri-implant bone.

Assessment of bone healing on tibial fractures treated with wire osteosynthesis associated or not with infrared laser light and biphasic ceramic bone graft (HATCP) and guided bone regeneration (GBR): Raman spectroscopy study

NASA Astrophysics Data System (ADS)

Bastos de Carvalho, Fabíola; Aciole, Gilberth Tadeu S.; Aciole, Jouber Mateus S.; Silveira, Landulfo, Jr.; Nunes dos Santos, Jean; Pinheiro, Antônio L. B.

2011-03-01

The aim of this study was to evaluate, through Raman spectroscopy, the repair of complete tibial fracture in rabbits fixed with wire osteosynthesis - WO, treated or not with infrared laser light (λ 780nm, 50mW, CW) associated or not to the use of HATCP and GBR. Surgical fractures were created under general anesthesia (Ketamine 0.4ml/Kg IP and Xilazine 0.2ml/Kg IP), on the tibia of 15 rabbits that were divided into 5 groups and maintained on individual cages, at day/night cycle, fed with solid laboratory pelted diet and had water ad libidum. On groups II, III, IV and V the fracture was fixed with WO. Animals of groups III and V were grafted with hydroxyapatite + GBR technique. Animals of groups IV and V were irradiated at every other day during two weeks (16J/cm2, 4 x 4J/cm2). Observation time was that of 30 days. After animal death the specimens were kept in liquid nitrogen for further analysis by Raman spectroscopy. Raman spectroscopy showed significant differences between groups (p<0.001). It is concluded that IR laser light was able to accelerate fracture healing and the association with HATCP and GBR resulted on increased deposition of calcium hydroxyapatite.

The developmental morphology of a "periosteal" ligament insertion: growth and maturation of the tibial insertion of the rabbit medial collateral ligament.

PubMed

Matyas, J R; Bodie, D; Andersen, M; Frank, C B

1990-05-01

The structural properties of ligament insertions change dramatically during growth and maturation, but little is known about their developmental anatomy. This study describes and quantifies changes in the gross and microscopic anatomy of the tibial insertion of the rabbit medial collateral ligament (MCL) during development and at skeletal maturity. Eighty animals were used for growth and descriptive studies. From this group, 27 animals, ranging in age from 1 to 24 months, were injected with fluorescent bone markers and their tibial insertions were processed undecalcified for histology. Sections were examined by polarized light and fluorescence microscopy to identify matrix and cells and to quantify mineral formation. Results showed that animals achieved histological skeletal maturity between 9 and 12 months of age. Body weights were a poor index of skeletal maturity. The tibial insertion was composed of five tissue layers, which changed proportions during growth and maturation. In immature animals, MCL fibers entered the periosteum; in older animals, MCL fibers were cemented to the tibia by advancing mineral. The tibial attachment of the MCL was thus transferred from the periosteum to the cortex during growth, suggesting that the term "periosteal insertion" is imprecise in adults. The hypothesis is put forward that these structural changes account for the reported increase in tensile failure of this insertion near skeletal maturity.

Blast effect on the lower extremities and its mitigation: a computational study.

PubMed

Dong, Liqiang; Zhu, Feng; Jin, Xin; Suresh, Mahi; Jiang, Binhui; Sevagan, Gopinath; Cai, Yun; Li, Guangyao; Yang, King H

2013-12-01

A series of computational studies were performed to investigate the response of the lower extremities of mounted soldiers under landmine detonation. A numerical human body model newly developed at Wayne State University was used to simulate two types of experimental studies and the model predictions were validated against test data in terms of the tibia axial force as well as bone fracture pattern. Based on the validated model, the minimum axial force causing tibia facture was found. Then a series of parametric studies was conducted to determine the critical velocity (peak velocity of the floor plate) causing tibia fracture at different upper/lower leg angles. In addition, to limit the load transmission through the vehicular floor, two types of energy absorbing materials, namely IMPAXX(®) foam and aluminum alloy honeycomb, were selected for floor matting. Their performances in terms of blast effect mitigation were compared using the validated numerical model, and it has been found that honeycomb is a more efficient material for blast injury prevention under the loading conditions studied. © 2013 Elsevier Ltd. All rights reserved.

First Reported Cases of Biomechanically Adaptive Bone Modeling in Non-Avian Dinosaurs.

PubMed

Cubo, Jorge; Woodward, Holly; Wolff, Ewan; Horner, John R

2015-01-01

Predator confrontation or predator evasion frequently produces bone fractures in potential prey in the wild. Although there are reports of healed bone injuries and pathologies in non-avian dinosaurs, no previously published instances of biomechanically adaptive bone modeling exist. Two tibiae from an ontogenetic sample of fifty specimens of the herbivorous dinosaur Maiasaura peeblesorum (Ornithopoda: Hadrosaurinae) exhibit exostoses. We show that these outgrowths are cases of biomechanically adaptive periosteal bone modeling resulting from overstrain on the tibia after a fibula fracture. Histological and biomechanical results are congruent with predictions derived from this hypothesis. Histologically, the outgrowths are constituted by radial fibrolamellar periosteal bone tissue formed at very high growth rates, as expected in a process of rapid strain equilibration response. These outgrowths show greater compactness at the periphery, where tensile and compressive biomechanical constraints are higher. Moreover, these outgrowths increase the maximum bending strength in the direction of the stresses derived from locomotion. They are located on the antero-lateral side of the tibia, as expected in a presumably bipedal one year old individual, and in the posterior position of the tibia, as expected in a presumably quadrupedal individual at least four years of age. These results reinforce myological evidence suggesting that Maiasaura underwent an ontogenetic shift from the primitive ornithischian bipedal condition when young to a derived quadrupedal posture when older.

First Reported Cases of Biomechanically Adaptive Bone Modeling in Non-Avian Dinosaurs

PubMed Central

Cubo, Jorge; Woodward, Holly; Wolff, Ewan; Horner, John R.

2015-01-01

Predator confrontation or predator evasion frequently produces bone fractures in potential prey in the wild. Although there are reports of healed bone injuries and pathologies in non-avian dinosaurs, no previously published instances of biomechanically adaptive bone modeling exist. Two tibiae from an ontogenetic sample of fifty specimens of the herbivorous dinosaur Maiasaura peeblesorum (Ornithopoda: Hadrosaurinae) exhibit exostoses. We show that these outgrowths are cases of biomechanically adaptive periosteal bone modeling resulting from overstrain on the tibia after a fibula fracture. Histological and biomechanical results are congruent with predictions derived from this hypothesis. Histologically, the outgrowths are constituted by radial fibrolamellar periosteal bone tissue formed at very high growth rates, as expected in a process of rapid strain equilibration response. These outgrowths show greater compactness at the periphery, where tensile and compressive biomechanical constraints are higher. Moreover, these outgrowths increase the maximum bending strength in the direction of the stresses derived from locomotion. They are located on the antero-lateral side of the tibia, as expected in a presumably bipedal one year old individual, and in the posterior position of the tibia, as expected in a presumably quadrupedal individual at least four years of age. These results reinforce myological evidence suggesting that Maiasaura underwent an ontogenetic shift from the primitive ornithischian bipedal condition when young to a derived quadrupedal posture when older. PMID:26153689

An Integrated Musculoskeletal-Finite-Element Model to Evaluate Effects of Load Carriage on the Tibia During Walking.

PubMed

Xu, Chun; Silder, Amy; Zhang, Ju; Hughes, Julie; Unnikrishnan, Ginu; Reifman, Jaques; Rakesh, Vineet

2016-10-01

Prior studies have assessed the effects of load carriage on the tibia. Here, we expand on these studies and investigate the effects of load carriage on joint reaction forces (JRFs) and the resulting spatiotemporal stress/strain distributions in the tibia. Using full-body motion and ground reaction forces from a female subject, we computed joint and muscle forces during walking for four load carriage conditions. We applied these forces as physiological loading conditions in a finite-element (FE) analysis to compute strain and stress. We derived material properties from computed tomography (CT) images of a sex-, age-, and body mass index-matched subject using a mesh morphing and mapping algorithm, and used them within the FE model. Compared to walking with no load, the knee JRFs were the most sensitive to load carriage, increasing by as much as 26.2% when carrying a 30% of body weight (BW) load (ankle: 16.4% and hip: 19.0%). Moreover, our model revealed disproportionate increases in internal JRFs with increases in load carriage, suggesting a coordinated adjustment in the musculature functions in the lower extremity. FE results reflected the complex effects of spatially varying material properties distribution and muscular engagement on tibial biomechanics during walking. We observed high stresses on the anterior crest and the medial surface of the tibia at pushoff, whereas high cumulative stress during one walking cycle was more prominent in the medioposterior aspect of the tibia. Our findings reinforce the need to include: (1) physiologically accurate loading conditions when modeling healthy subjects undergoing short-term exercise training and (2) the duration of stress exposure when evaluating stress-fracture injury risk. As a fundamental step toward understanding the instantaneous effect of external loading, our study presents a means to assess the relationship between load carriage and bone biomechanics.

The healing stages of an intramedullary implanted tibia: A stress strain comparative analysis of the calcification process

PubMed Central

Filardi, Vincenzo

2015-01-01

Aims The extended usage of unreamed tibial nailing resulted in reports of an increased rate of complications, especially for the distal portion of the tibia. Unreamed nailing favours biology at the expense of the achievable mechanical stability, it is therefore of interest to define the limits of the clinical indications for this method. Extra-articular fractures of the distal tibial metaphysis, meta-diaphyseal junction, and adjacent diaphysis are distinct in their management from impaction derived ‘‘pilon’’ type fractures and mid-diaphyseal fractures. The goals of this work were to gain a thorough understanding of the load-sharing mechanism between unreamed nail and bones in a fractured tibia. With this purpose a complete model of the human leg was realised, simulating a mid-diaphyseal fracture, classified as A2 type 1, according to the AO classification. The analysis of the entire chain allows to have a complete picture of the stress distribution and of the most stressed bones and soft tissues, but, more importantly can overcome problems connected with boundary conditions imposed at single bony components. Methods Model consists of six bony structures: pelvis, femur, patella, fibula, tibia, and a simplified lump of the feet, configured in a standing up position. Their articular cartilage layers, were simulated by 3D membranes of opportune stiffness connecting the different segments. Moreover an unreamed intra-medullary nail Expert Tibial Nail (DePuy Synthes®) stabilized the fractured tibia. A load of 700 N has been applied at the top of pelvis and a part the feet, at the tip, was rigidly fixed. Five different contact interfaces have been imposed at the different bony surfaces in contact. Results Three different conditions were analysed: the initially healthy tibia, the A2 type 1 fractured tibia with the Expert tibial nail implanted, and the follow up stage after complete healing of tibia. Non-linear finite element analysis of the models were performed with Abaqus version 5.4 (Hibbitt, Karlsson and Sorensen, Inc., Pawtucket, RI) using the geometric non linearity and automatic time stepping options. Conclusion The obtained results reveal interesting consequences deriving by taking into account how the stress shielding can influence the integrity and resistance of bones, in order to identify the mechanical reasons for the unfavourable clinical results, and to identify borderline indications due to biomechanical factors. The evolution of treatment options for these fractures has been closely linked to developments in implant technology and surgical technique. Further developments in this area, particularly with respect to minimally invasive plating techniques and nail design are ongoing. PMID:26719629

Customized Knee Prosthesis in Treatment of Giant Cell Tumors of the Proximal Tibia: Application of 3-Dimensional Printing Technology in Surgical Design.

PubMed

Luo, Wenbin; Huang, Lanfeng; Liu, He; Qu, Wenrui; Zhao, Xin; Wang, Chenyu; Li, Chen; Yu, Tao; Han, Qing; Wang, Jincheng; Qin, Yanguo

2017-04-07

BACKGROUND We explored the application of 3-dimensional (3D) printing technology in treating giant cell tumors (GCT) of the proximal tibia. A tibia block was designed and produced through 3D printing technology. We expected that this 3D-printed block would fill the bone defect after en-bloc resection. Importantly, the block, combined with a standard knee joint prosthesis, provided attachments for collateral ligaments of the knee, which can maintain knee stability. MATERIAL AND METHODS A computed tomography (CT) scan was taken of both knee joints in 4 patients with GCT of the proximal tibia. We developed a novel technique - the real-size 3D-printed proximal tibia model - to design preoperative treatment plans. Hence, with the application of 3D printing technology, a customized proximal tibia block could be designed for each patient individually, which fixed the bone defect, combined with standard knee prosthesis. RESULTS In all 4 cases, the 3D-printed block fitted the bone defect precisely. The motion range of the affected knee was 90 degrees on average, and the soft tissue balance and stability of the knee were good. After an average 7-month follow-up, the MSTS score was 19 on average. No sign of prosthesis fracture, loosening, or other relevant complications were detected. CONCLUSIONS This technique can be used to treat GCT of the proximal tibia when it is hard to achieve soft tissue balance after tumor resection. 3D printing technology simplified the design and manufacturing progress of custom-made orthopedic medical instruments. This new surgical technique could be much more widely applied because of 3D printing technology.

Validation of a measuring technique with computed tomography for cement penetration into trabecular bone underneath the tibial tray in total knee arthroplasty on a cadaver model

PubMed Central

2014-01-01

Background In total knee arthroplasty (TKA), cement penetration between 3 and 5 mm beneath the tibial tray is required to prevent loosening of the tibia component. The objective of this study was to develop and validate a reliable in vivo measuring technique using CT imaging to assess cement distribution and penetration depth in the total area underneath a tibia prosthesis. Methods We defined the radiodensity ranges for trabecular tibia bone, polymethylmethacrylate (PMMA) cement and cement-penetrated trabecular bone and measured the percentages of cement penetration at various depths after cementing two tibia prostheses onto redundant femoral heads. One prosthesis was subsequently removed to examine the influence of the metal tibia prostheses on the quality of the CT images. The percentages of cement penetration in the CT slices were compared with percentages measured with photographs of the corresponding transversal slices. Results Trabecular bone and cement-penetrated trabecular bone had no overlap in quantitative scale of radio-density. There was no significant difference in mean HU values when measuring with or without the tibia prosthesis. The percentages of measured cement-penetrated trabecular bone in the CT slices of the specimen were within the range of percentages that could be expected based on the measurements with the photographs (p = 0.04). Conclusions CT scan images provide valid results in measuring the penetration and distribution of cement into trabecular bone underneath the tibia component of a TKA. Since the proposed method does not turn metal elements into artefacts, it enables clinicians to assess the width and density of the cement mantle in vivo and to compare the results of different cementing methods in TKA. PMID:25158996

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.

Raman spectroscopy of bone metastasis

NASA Astrophysics Data System (ADS)

Esmonde-White, Karen A.; Sottnik, Joseph; Morris, Michael; Keller, Evan

2012-02-01

Raman spectroscopy of bone has been used to characterize chemical changes occurring in diseases such as osteoporosis, osteoarthritis and osteomyelitis. Metastasis of cancer into bone causes changes to bone quality that are similar to those observed in osteoporosis, such as decreased bone strength, but with an accelerated timeframe. In particular, osteolytic (bone degrading) lesions in bone metastasis have a marked effect on patient quality of life because of increased risk of fractures, pain, and hypercalcemia. We use Raman spectroscopy to examine bone from two different mouse models of osteolytic bone metastasis. Raman spectroscopy measures physicochemical information which cannot be obtained through standard biochemical and histological measurements. This study was reviewed and approved by the University of Michigan University Committee on the Care and Use of Animals. Two mouse models of prostate cancer bone metastasis, RM1 (n=3) and PC3-luc (n=4) were examined. Tibiae were injected with RM1 or PC3-luc cancer cells, while the contralateral tibiae received a placebo injection for use as controls. After 2 weeks of incubation, the mice were sacrificed and the tibiae were examined by Raman microspectroscopy (λ=785 nm). Spectroscopic markers corresponding to mineral stoichiometry, bone mineralization, and mineral crystallinity were compared in spectra from the cancerous and control tibiae. X-ray imaging of the tibia confirmed extensive osteolysis in the RM1 mice, with tumor invasion into adjoining soft tissue and moderate osteolysis in the PC3-luc mice. Raman spectroscopic markers indicate that osteolytic lesions are less mineralized than normal bone tissue, with an altered mineral stoichiometry and crystallinity.

Experimental models for contamination of titanium surfaces and disinfection protocols.

PubMed

Sousa, Vanessa; Mardas, Nikos; Spratt, David; Boniface, David; Dard, Michel; Donos, Nikolaos

2016-10-01

The aim of this pilot study was to describe an in vitro model of peri-implantitis microcosm for contamination of titanium surfaces and an in vivo model for evaluating different disinfection strategies of titanium surfaces. Biofilms were grown in vitro for 30 days on sandblasted large-grit acid-etched (SLA) Ti discs (n = 69) in a constant depth film fermentor (CDFF) associated with peri-implantitis conditions. Four Swedish loop rabbits were randomly allocated in three test groups (T 1 , T 2 , T 3 ) and one control group (C). In group C, two sterile SLA Ti discs were implanted/fixed in each tibia. In the test groups (to evaluate the potential of different surface disinfection techniques), one sterile and three previously disinfected SLA Ti discs were placed following different disinfection protocols: group T 1 : the discs were treated with a titanium brush - TiB; group T 2 : the discs were treated with the combination of TiB and photodynamic therapy; and group T 3 : the discs were treated with TiB and 1%NaOCl plus 0.2%CHX. Tensile strength test and qualitative histological analysis were performed on all 16 discs after 4 weeks of healing. Thirty days following CDFF emulating peri-implantitis microcosm, all SLA Ti discs had a mean total viable aerobes and facultative anaerobes count of 8.06 log 10  CFU/biofilm and anaerobes 8.32 log 10  CFU/biofilm. Before implantation/fixation on the tibia, differences of log 10  CFU/biofilm counts between control and test groups after post hoc adjustment were highly significant (P < 0.001). In the in vivo analysis, group C exhibited the highest tensile strength (67.60 N [25.64-127.02]) and the histological sections revealed the presence of dense mature bone in direct contact with the disc surface. The analysis at the test groups showed that T 2 presented with the highest tensile strength in comparison with the other two test groups. The in vitro model used in this study provides a valuable and reproducible tool for evaluating the in vitro dynamics of the peri-implantitis microcosm biofilm and for contaminating in a reproducible manner titanium surfaces. At the same time, the in vivo model used in this study provides a standardised mode of evaluating disinfection modalities of previously infected titanium surfaces. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

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.

Use of micro-CT-based finite element analysis to accurately quantify peri-implant bone strains: a validation in rat tibiae.

PubMed

Torcasio, Antonia; Zhang, Xiaolei; Van Oosterwyck, Hans; Duyck, Joke; van Lenthe, G Harry

2012-05-01

Although research has been addressed at investigating the effect of specific loading regimes on bone response around the implant, a precise quantitative understanding of the local mechanical response close to the implant site is still lacking. This study was aimed at validating micro-CT-based finite element (μFE) models to assess tissue strains after implant placement in a rat tibia. Small implants were inserted at the medio-proximal site of 8 rat tibiae. The limbs were subjected to axial compression loading; strain close to the implant was measured by means of strain gauges. Specimen-specific μFE models were created and analyzed. For each specimen, 4 different models were created corresponding to different representations of the bone-implant interface: bone and implant were assumed fully osseointegrated (A); a low stiffness interface zone was assumed with thickness of 40 μm (B), 80 μm (C), and 160 μm (D). In all cases, measured and computational strains correlated highly (R (2) = 0.95, 0.92, 0.93, and 0.95 in A, B, C, and D, respectively). The averaged calculated strains were 1.69, 1.34, and 1.15 times higher than the measured strains for A, B, and C, respectively, and lower than the experimental strains for D (factor = 0.91). In conclusion, we demonstrated that specimen-specific FE analyses provide accurate estimates of peri-implant bone strains in the rat tibia loading model. Further investigations of the bone-implant interface are needed to quantify implant osseointegration.

Does implant coating with antibacterial-loaded hydrogel reduce bacterial colonization and biofilm formation in vitro?

PubMed

Drago, Lorenzo; Boot, Willemijn; Dimas, Kostantinos; Malizos, Kostantinos; Hänsch, Gertrud M; Stuyck, Jos; Gawlitta, Debby; Romanò, Carlo L

2014-11-01

Implant-related infections represent one of the most severe complications in orthopaedics. A fast-resorbable, antibacterial-loaded hydrogel may reduce or prevent bacterial colonization and biofilm formation of implanted biomaterials. We asked: (1) Is a fast-resorbable hydrogel able to deliver antibacterial compounds in vitro? (2) Can a hydrogel (alone or antibacterial-loaded) coating on implants reduce bacterial colonization? And (3) is intraoperative coating feasible and resistant to press-fit implant insertion? We tested the ability of Disposable Antibacterial Coating (DAC) hydrogel (Novagenit Srl, Mezzolombardo, Italy) to deliver antibacterial agents using spectrophotometry and a microbiologic assay. Antibacterial and antibiofilm activity were determined by broth microdilution and a crystal violet assay, respectively. Coating resistance to press-fit insertion was tested in rabbit tibias and human femurs. Complete release of all tested antibacterial compounds was observed in less than 96 hours. Bactericidal and antibiofilm effect of DAC hydrogel in combination with various antibacterials was shown in vitro. Approximately 80% of the hydrogel coating was retrieved on the implant after press-fit insertion. Implant coating with an antibacterial-loaded hydrogel reduces bacterial colonization and biofilm formation in vitro. A fast-resorbable, antibacterial-loaded hydrogel coating may help prevent implant-related infections in orthopaedics. However, further validation in animal models and properly controlled human studies is required.

Application of in vivo micro-computed tomography in the temporal characterisation of subchondral bone architecture in a rat model of low-dose monosodium iodoacetate-induced osteoarthritis

PubMed Central

2011-01-01

Introduction Osteoarthritis (OA) is a complex, multifactorial joint disease affecting both the cartilage and the subchondral bone. Animal models of OA aid in the understanding of the pathogenesis of OA and testing suitable drugs for OA treatment. In this study we characterized the temporal changes in the tibial subchondral bone architecture in a rat model of low-dose monosodium iodoacetate (MIA)-induced OA using in vivo micro-computed tomography (CT). Methods Male Wistar rats received a single intra-articular injection of low-dose MIA (0.2 mg) in the right knee joint and sterile saline in the left knee joint. The animals were scanned in vivo by micro-CT at two, six, and ten weeks post-injection, analogous to early, intermediate, and advanced stages of OA, to assess architectural changes in the tibial subchondral bone. The articular cartilage changes in the tibiae were assessed macroscopically and histologically at ten weeks post-injection. Results Interestingly, tibiae of the MIA-injected knees showed significant bone loss at two weeks, followed by increased trabecular thickness and separation at six and ten weeks. The trabecular number was decreased at all time points compared to control tibiae. The tibial subchondral plate thickness of the MIA-injected knee was increased at two and six weeks and the plate porosity was increased at all time points compared to control. At ten weeks, histology revealed loss of proteoglycans, chondrocyte necrosis, chondrocyte clusters, cartilage fibrillation, and delamination in the MIA-injected tibiae, whereas the control tibiae showed no changes. Micro-CT images and histology showed the presence of subchondral bone sclerosis, cysts, and osteophytes. Conclusions These findings demonstrate that the low-dose MIA rat model closely mimics the pathological features of progressive human OA. The low-dose MIA rat model is therefore suitable to study the effect of therapeutic drugs on cartilage and bone in a non-trauma model of OA. In vivo micro-CT is a non-destructive imaging technique that can track structural changes in the tibial subchondral bone in this animal model, and could also be used to track changes in bone in preclinical drug intervention studies for OA treatments. PMID:22185204

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.

Prediction of risk of fracture in the tibia due to altered bone mineral density distribution resulting from disuse: a finite element study.

PubMed

Gislason, Magnus K; Coupaud, Sylvie; Sasagawa, Keisuke; Tanabe, Yuji; Purcell, Mariel; Allan, David B; Tanner, K Elizabeth

2014-02-01

The disuse-related bone loss that results from immobilisation following injury shares characteristics with osteoporosis in post-menopausal women and the aged, with decreases in bone mineral density leading to weakening of the bone and increased risk of fracture. The aim of this study was to use the finite element method to: (i) calculate the mechanical response of the tibia under mechanical load and (ii) estimate of the risk of fracture; comparing between two groups, an able-bodied group and spinal cord injury patients group suffering from varying degrees of bone loss. The tibiae of eight male subjects with chronic spinal cord injury and those of four able-bodied age-matched controls were scanned using multi-slice peripheral quantitative computed tomography. Images were used to develop full three-dimensional models of the tibiae in Mimics (Materialise) and exported into Abaqus (Simulia) for calculation of stress distribution and fracture risk in response to specified loading conditions - compression, bending and torsion. The percentage of elements that exceeded a calculated value of the ultimate stress provided an estimate of the risk of fracture for each subject, which differed between spinal cord injury subjects and their controls. The differences in bone mineral density distribution along the tibia in different subjects resulted in different regions of the bone being at high risk of fracture under set loading conditions, illustrating the benefit of creating individual material distribution models. A predictive tool can be developed based on these models, to enable clinicians to estimate the amount of loading that can be safely allowed onto the skeletal frame of individual patients who suffer from extensive musculoskeletal degeneration (including spinal cord injury, multiple sclerosis and the ageing population). The ultimate aim is to reduce fracture occurrence in these vulnerable groups.

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.

Influence of hydroxyapatite granule size, porosity, and crystallinity on tissue reaction in vivo. Part A: synthesis, characterization of the materials, and SEM analysis.

PubMed

Maté Sánchez de Val, José E; Calvo-Guirado, José L; Gómez-Moreno, Gerardo; Pérez-Albacete Martínez, Carlos; Mazón, Patricia; De Aza, Piedad N

2016-11-01

The aim of this study was the synthesis and analysis of the tissue reaction to three different Hydroxyapatite (HA)-based bone substitute materials differing only in granule size, porosity, and crystallinity through an animal experimental model at 60 days. Three different HA-based biomaterials were synthesized and characterized by X-ray diffraction, SEM, and EDS analysis, the resultant product was ground in three particle sizes: Group I (2000-4000 μm), Group II (1000-2000 μm), and Group III (600-1000 μm). Critical size defects were created in both tibias of 15 rabbits. Four defects per rabbit for a total of 60 defects were grafted with the synthesized materials as follows: Group I (15 defects), Group II (15 defects), Group III (15 defects), and empty (15 defects control). After animals sacrifice at 60 days samples were obtained and processed for SEM and EDS evaluation of Ca/P ratios, elemental mapping was performed to determine the chemical degradation process and changes to medullary composition in all the four study groups. The tendency for the density was to increase with the increasing annealing temperature; in this way it was possible to observe that the sample that shows highest crystallinity and crystal size corresponding to that of group I. The SEM morphological examination showed that group III implant showed numerous resorption regions, group II implant presented an average resorption rate of all the implants. The group I displayed smoother surface features, in comparison with the other two implants. The data from this study show that changing the size, porosity, and crystallinity of one HA-based bone substitute material can influence the integration of the biomaterials within the implantation site and the new bone formation. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effect of insertion torque on titanium implant osseointegration: an animal experimental study.

PubMed

Duyck, Joke; Roesems, Rutger; Cardoso, Marcio V; Ogawa, Toru; De Villa Camargos, Germana; Vandamme, Katleen

2015-02-01

To evaluate the effect of implant insertion torque on the peri-implant bone healing and implant osseointegration. Bilaterally in the tibia of five adult New Zealand white rabbits, 20 implants were installed, subdivided into four groups, corresponding to two insertion torque conditions (low, < 10 Ncm vs. high > 50 Ncm) and 2 experimental periods (2 weeks vs. 4 weeks of healing). The implant insertion torque was determined by the surgical drill diameter relative to the implant diameter. Implant osseointegration was evaluated by quantitative histology (bone-to-implant contact with host bone [BIC-host], with neoformed bone [BIC-de novo], with both bone types [BIC-total], and peri-implant bone [BA/TA]). Every response was modelled over time using GEE (general estimation equation) with an unstructured variance-covariance matrix to correct for dependency between the measurements from one animal. The statistical significance level of α = 0.05 was applied. Significantly, more BIC-host and BIC-total were recorded for H implants compared with L implants after 2 week of healing (P = 0.010 and P = 0.0001, respectively). However, this result was no longer found for the extended healing period. Furthermore, BIC-total significantly increased over time for L implants (P < 0.00001). In contrast, the significant increase in BA/TA over time was found for H implants (P < 0.01). Finally, H insertion torque led to an increased BA/TA after 4 week of healing (P < 0.02) compared with the L insertion protocol. L insertion torque implants installed in the rabbit tibial bone osseointegrate with considerable de novo bone formation. This bone neoformation enables L implants to catch up, already during the early osseointegration stage, the initial inferior amount BIC contact compared with that of H implants. A negative impact of the created strain environment accompanying H insertion torque implant installation on the biological process of osseointegration could not be observed, at least not at tissue level. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Bone mineral density, chemical composition and biomechanical properties of the tibia of female rats exposed to cadmium since weaning up to skeletal maturity.

PubMed

Brzóska, M M; Majewska, K; Moniuszko-Jakoniuk, J

2005-10-01

The influence of exposure to cadmium (Cd) during skeletal development on the risk of bone fractures at the stage of skeletal maturity was investigated on a female rat model of human exposure. The tibias of rats treated with 1, 5 or 50 mg Cd/l in drinking water for 3, 6, 9 and 12 months (since weaning) were used. The exposure to Cd dose- and time-dependently influenced the tibia bone mineral density (BMD) and chemical composition. In skeletally matured animals, at each level of the exposure to Cd, the BMD at the whole tibia and its diaphysis as well as the percentage of minerals content in the bone, including the content of zinc, copper and iron, were decreased compared to control. Moreover, in the 50 mg Cd/l group, the percentage of organic components content increased. The Cd-induced changes, at all levels of exposure, resulted in weakening in the yield strength and fracture strength of the tibia (a three-point bending test of the diaphysis and compression test with vertical loading) of the skeletally matured females. A very important and clinically useful finding of this study is that a decrease (even by several percent) in the tibia BMD results in weakness in the bone biomechanical properties and that the BMD may predict the risk of its fracture at the exposure to Cd. Moreover, the results together with our previous findings seem to suggest that tibia, due to higher vulnerability of its diaphysis, compared to the femoral diaphysis, to damage by Cd may be more useful than femur to investigate the effect of Cd on the cortical bone. The present study revealed that a low exposure to Cd (1 mg Cd/l), corresponding to low human environmental exposure, during the skeletal development affects the tibia mineral status leading to weakening in its mechanical properties at the skeletal maturity. The findings allow for the conclusion that environmental exposure to Cd during childhood and adolescence may enhance the risk of low BMD and fractures at adulthood.

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.

External torsion in a proximal tibia and internal torsion in a distal tibia occur independently in varus osteoarthritic knees compared to healthy knees.

PubMed

Mochizuki, Tomoharu; Tanifuji, Osamu; Koga, Yoshio; Hata, Ryosuke; Mori, Takahiro; Nishino, Katsutoshi; Sato, Takashi; Kobayashi, Koichi; Omori, Go; Sakamoto, Makoto; Tanabe, Yuji; Endo, Naoto

2017-05-01

The relative torsional angle of the distal tibia is dependent on a deformity of the proximal tibia, and it is a commonly used torsional parameter to describe deformities of the tibia; however, this parameter cannot show the location and direction of the torsional deformity in the entire tibia. This study aimed to identify the detailed deformity in the entire tibia via a coordinate system based on the diaphysis of the tibia by comparing varus osteoarthritic knees to healthy knees. In total, 61 limbs in 58 healthy subjects (age: 54 ± 18 years) and 55 limbs in 50 varus osteoarthritis (OA) subjects (age: 72 ± 7 years) were evaluated. The original coordinate system based on anatomic points only from the tibial diaphysis was established. The evaluation parameters were 1) the relative torsion in the distal tibia to the proximal tibia, 2) the proximal tibial torsion relative to the tibial diaphysis, and 3) the distal tibial torsion relative to the tibial diaphysis. The relative torsion in the distal tibia to the proximal tibia showed external torsion in both groups, while the external torsion was lower in the OA group than in the healthy group (p < 0.0001). The proximal tibial torsion relative to the tibial diaphysis had a higher external torsion in the OA group (p = 0.012), and the distal tibial torsion relative to the tibial diaphysis had a higher internal torsion in the OA group (p = 0.004) in comparison to the healthy group. The reverse torsional deformity, showing a higher external torsion in the proximal tibia and a higher internal torsion in the distal tibia, occurred independently in the OA group in comparison to the healthy group. Clinically, this finding may prove to be a pathogenic factor in varus osteoarthritic knees. Level Ⅲ. Copyright © 2017 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.

Pathomorphism of spiral tibial fractures in computed tomography imaging.

PubMed

Guzik, Grzegorz

2011-01-01

Spiral fractures of the tibia are virtually homogeneous with regard to their pathomorphism. The differences that are seen concern the level of fracture of the fibula, and, to a lesser extent, the level of fracture of the tibia, the length of fracture cleft, and limb shortening following the trauma. While conventional radiographs provide sufficient information about the pathomorphism of fractures, computed tomography can be useful in demonstrating the spatial arrangement of bone fragments and topography of soft tissues surrounding the fracture site. Multiple cross-sectional computed tomography views of spiral fractures of the tibia show the details of the alignment of bone chips at the fracture site, axis of the tibial fracture cleft, and topography of soft tissues that are not visible on standard radiographs. A model of a spiral tibial fracture reveals periosteal stretching with increasing spiral and longitudinal displacement. The cleft in tibial fractures has a spiral shape and its line is invariable. Every spiral fracture of both crural bones results in extensive damage to the periosteum and may damage bellies of the long flexor muscle of toes, flexor hallucis longus as well as the posterior tibial muscle. Computed tomography images of spiral fractures of the tibia show details of damage that are otherwise invisible on standard radiographs. Moreover, CT images provide useful information about the spatial location of the bone chips as well as possible threats to soft tissues that surround the fracture site. Every spiral fracture of the tibia is associated with disruption of the periosteum. 1. Computed tomography images of spiral fractures of the tibia show details of damage otherwise invisible on standard radiographs, 2. The sharp end of the distal tibial chip can damage the tibialis posterior muscle, long flexor muscles of the toes and the flexor hallucis longus, 3. Every spiral fracture of the tibia is associated with disruption of the periosteum.

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.

Biomechanics of jumping in the flea.

PubMed

Sutton, Gregory P; Burrows, Malcolm

2011-03-01

It has long been established that fleas jump by storing and releasing energy in a cuticular spring, but it is not known how forces from that spring are transmitted to the ground. One hypothesis is that the recoil of the spring pushes the trochanter onto the ground, thereby generating the jump. A second hypothesis is that the recoil of the spring acts through a lever system to push the tibia and tarsus onto the ground. To decide which of these two hypotheses is correct, we built a kinetic model to simulate the different possible velocities and accelerations produced by each proposed process and compared those simulations with the kinematics measured from high-speed images of natural jumping. The in vivo velocity and acceleration kinematics are consistent with the model that directs ground forces through the tibia and tarsus. Moreover, in some natural jumps there was no contact between the trochanter and the ground. There were also no observable differences between the kinematics of jumps that began with the trochanter on the ground and jumps that did not. Scanning electron microscopy showed that the tibia and tarsus have spines appropriate for applying forces to the ground, whereas no such structures were seen on the trochanter. Based on these observations, we discount the hypothesis that fleas use their trochantera to apply forces to the ground and conclude that fleas jump by applying forces to the ground through the end of the tibiae.

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

Maternal Consumption of Hesperidin and Naringin Flavanones Exerts Transient Effects to Tibia Bone Structure in Female CD-1 Offspring

PubMed Central

Sacco, Sandra M.; Saint, Caitlin; LeBlanc, Paul J.; Ward, Wendy E.

2017-01-01

Hesperidin (HSP) and naringin (NAR), flavanones rich in citrus fruits, support skeletal integrity in adult and aging rodent models. This study determined whether maternal consumption of HSP and NAR favorably programs bone development, resulting in higher bone mineral density (BMD) and greater structure and biomechanical strength (i.e., peak load) in female offspring. Female CD-1 mice were fed a control diet or a HSP + NAR diet five weeks before pregnancy and throughout pregnancy and lactation. At weaning, female offspring were fed a control diet until six months of age. The structure and BMD of the proximal tibia were measured longitudinally using in vivo micro-computed tomography at 2, 4, and 6 months of age. The trabecular bone structure at two and four months and the trabecular BMD at four months were compromised at the proximal tibia in mice exposed to HSP and NAR compared to the control diet (p < 0.001). At six months of age, these differences in trabecular structure and BMD at the proximal tibia had disappeared. At 6 months of age, the tibia midpoint peak load, BMD, structure, and the peak load of lumbar vertebrae and femurs were similar (p > 0.05) between the HSP + NAR and control groups. In conclusion, maternal consumption of HSP and NAR does not enhance bone development in female CD-1 offspring. PMID:28282882

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 estimation of the rates of lead exchange between body compartments of smelter employees.

PubMed

Behinaein, Sepideh; Chettle, David R; Egden, Lesley M; McNeill, Fiona E; Norman, Geoff; Richard, Norbert; Stever, Susan

2014-07-01

The overwhelming proportion of the mass of lead (Pb) is stored in bone and the residence time of Pb in bone is much longer than that in other tissues. Hence, in a metabolic model that we used to solve the differential equations governing the transfer of lead between body compartments, three main compartments are involved: blood (as a transfer compartment), cortical bone (tibia), and trabecular bone (calcaneus). There is a bidirectional connection between blood and the other two compartments. A grid search chi-squared minimization method was used to estimate the initial values of lead transfer rate values from tibia (λTB) and calcaneus (λCB) to blood of 209 smelter employees whose bone lead measurements are available from 1994, 1999, and 2008, and their blood lead level from 1967 onwards (depending on exposure history from once per month to once per year), and then the initial values of kinematic parameters were used to develop multivariate models in order to express λTB and λCB as a function of employment time, age, body lead contents and their interaction. We observed a significant decrease in the transfer rate of lead from bone to blood with increasing body lead contents. The model was tested by calculating the bone lead concentration in 1999 and 2008, and by comparing those values with the measured ones. A good agreement was found between the calculated and measured tibia/calcaneus lead values. Also, we found that the transfer rate of lead from tibia to blood can be expressed solely as a function of cumulative blood lead index.

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

Stunting, adiposity, and the individual-level "dual burden" among urban lowland and rural highland Peruvian children.

PubMed

Pomeroy, Emma; Stock, Jay T; Stanojevic, Sanja; Miranda, J Jaime; Cole, Tim J; Wells, Jonathan C K

2014-01-01

The causes of the "dual burden" of stunting and obesity remain unclear, and its existence at the individual level varies between populations. We investigate whether the individual dual burden differentially affects low socioeconomic status Peruvian children from contrasting environments (urban lowlands and rural highlands), and whether tibia length can discount the possible autocorrelation between adiposity proxies and height due to height measurement error. Stature, tibia length, weight, and waist circumference were measured in children aged 3-8.5 years (n = 201). Height and body mass index (BMI) z scores were calculated using international reference data. Age-sex-specific centile curves were also calculated for height, BMI, and tibia length. Adiposity proxies (BMI z score, waist circumference-height ratio (WCHtR)) were regressed on height and also on tibia length z scores. Regression model interaction terms between site (highland vs. lowland) and height indicate that relationships between adiposity and linear growth measures differed significantly between samples (P < 0.001). Height was positively associated with BMI among urban lowland children, and more weakly with WCHtR. Among rural highland children, height was negatively associated with WCHtR but unrelated to BMI. Similar results using tibia length rather than stature indicate that stature measurement error was not a major concern. Lowland and rural highland children differ in their patterns of stunting, BMI, and WCHtR. These contrasts likely reflect environmental differences and overall environmental stress exposure. Tibia length or knee height can be used to assess the influence of measurement error in height on the relationship between stature and BMI or WCHtR. Copyright © 2014 Wiley Periodicals, Inc.

Comparison of metal concentrations in rat tibia tissues with various metallic implants.

PubMed

Okazaki, Yoshimitsu; Gotoh, Emiko; Manabe, Takeshi; Kobayashi, Kihei

2004-12-01

To compare metal concentrations in tibia tissues with various metallic implants, SUS316L stainless steel, Co-Cr-Mo casting alloy, and Ti-6Al-4V and V-free Ti-15Zr-4Nb-4Ta alloys were implanted into the rat tibia for up to 48 weeks. After the implant was removed from the tibia by decalcification, the tibia tissues near the implant were lyophilized. Then the concentrations of metals in the tibia tissues by microwave acid digestion were determined by inductively coupled plasma-mass spectrometry. Fe concentrations were determined by graphite-furnace atomic absorption spectrometry. The Fe concentration in the tibia tissues with the SUS316L implant was relatively high, and it rapidly increased up to 12 weeks and then decreased thereafter. On the other hand, the Co concentration in the tibia tissues with the Co-Cr-Mo implant was lower, and it increased up to 24 weeks and slightly decreased at 48 weeks. The Ni concentration in the tibia tissues with the SUS316L implant increased up to 6 weeks and then gradually decreased thereafter. The Cr concentration tended to be higher than the Co concentration. This Cr concentration linearly increased up to 12 weeks and then decreased toward 48 weeks in the tibia tissues with the SUS316L or Co-Cr-Mo implant. Minute quantities of Ti, Al and V in the tibia tissues with the Ti-6Al-4V implant were found. The Ti concentration in the tibia tissues with the Ti-15Zr-4Nb-4Ta implant was lower than that in the tibia tissues with the Ti-6Al-4V implant. The Zr, Nb and Ta concentrations were also very low. The Ti-15Zr-4Nb-4Ta alloy with its low metal release in vivo is considered advantageous for long-term implants.

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

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

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

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

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.

Kinematic analysis of total knee prosthesis designed for Asian population.

PubMed

Low, F H; Khoo, L P; Chua, C K; Lo, N N

2000-01-01

In designing a total knee replacement (TKR) prosthesis catering for the Asian population, 62 sets of femur were harvested and analyzed. The morphometrical data obtained were found to be in good agreement with dimensions typical of the Asian knee and has reaffirmed the fact that Caucasian knees are generally larger than Asian knees. Subsequently, these data when treated using a multivariate statistical technique resulted in the establishment of major design parameters for six different sizes of femoral implants. An extra-small implant size with established dimensions and geometrical shape has surfaced from the study. The differences between the Asian knees and the Caucasian knees are discussed. Employing the established femoral dimensions and motion path of the knee joint, the articulating tibia profile was generated. All the sizes of implants were modeled using a computer-aided software package. Thereupon, these models that accurately fits the local Asian knee were transported into a dynamic and kinematic analysis software package. The tibiofemoral joint was modeled successfully as a slide curve joint to study intuitively the motion of the femur when articulating on the tibia surface. An optimal tibia profile could be synthesized to mimic the natural knee path motion. Details of the analysis are presented and discussed.

A Passive and Wireless Sensor for Bone Plate Strain Monitoring.

PubMed

Tan, Yisong; Hu, Jiale; Ren, Limin; Zhu, Jianhua; Yang, Jiaqi; Liu, Di

2017-11-16

This paper reports on a sensor for monitoring bone plate strain in real time. The detected bone plate strain could be used for judging the healing state of fractures in patients. The sensor consists of a magnetoelastic material, which can be wirelessly connected and passively embedded. In order to verify the effectiveness of the sensor, a tibia-bone plate-screw (TBS) model was established using the finite element analysis method. A variation of the bone plate strain was obtained via this model. A goat hindquarter tibia was selected as the bone fracture model in the experiment. The tibia was fixed on a high precision load platform and an external force was applied. Bone plate strain variation during the bone fracture healing process was acquired with sensing coils. Simulation results indicated that bone plate strain decreases as the bone gradually heals, which is consistent with the finite element analysis results. This validated the soundness of the sensor reported here. This sensor has wireless connections, no in vivo battery requirement, and long-term embedding. These results can be used not only for clinical practices of bone fracture healing, but also for bone fracture treatment and rehabilitation equipment design.

Improved Healing of Large, Osseous, Segmental Defects by Reverse Dynamization: Evaluation in a Sheep Model

DTIC Science & Technology

2014-10-01

initiated. One such fixator has been tested on a cadaveric sheep tibia. In the unlocked, loose position, the axial stiffness of the tibia and fixator...suggested by our previous studies using rats. This aspect of the project is the present focus of attention, and additional cadaver legs will be tested...characterize external fixators). A 3 mm tibial defect was created in the leg of a cadaveric sheep, and stabilized with an experimental external

The relationship of bone and blood lead to hypertension: Further analyses of the normative aging study data

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

Hu, H.; Kim, Rokho; Korrick, S.

1996-12-31

In an earlier report based on participants in the Veterans Administration Normative Aging Study, we found a significant association between the risk of hypertension and lead levels in tibia. To examine the possible confounding effects of education and occupation, we considered in this study five levels of education and three levels of occupation as independent variables in the statistical model. Of 1,171 active subjects seen between August 1991 and December 1994, 563 provided complete data for this analysis. In the initial logistic regression model, acre and body mass index, family history of hypertension, and dietary sodium intake, but neither cumulativemore » smoking nor alcohol ingestion, conferred increased odds ratios for being hypertensive that were statistically significant. When the lead biomarkers were added separately to this initial logistic model, tibia lead and patella lead levels were associated with significantly elevated odds ratios for hypertension. In the final backward elimination logistic regression model that included categorical variables for education and occupation, the only variables retained were body mass index, family history of hypertension, and tibia lead level. We conclude that education and occupation variables were not confounding the association between the lead biomarkers and hypertension that we reported previously. 27 refs., 3 tabs.« less

Collagen Peptides from Crucian Skin Improve Calcium Bioavailability and Structural Characterization by HPLC-ESI-MS/MS.

PubMed

Hou, Tao; Liu, Yanshuang; Guo, Danjun; Li, Bo; He, Hui

2017-10-11

The effects of collagen peptides (CPs), which are derived from crucian skin, were investigated in a retinoic acid-induced bone loss model. The level of serum bone alkaline phosphatase (BALP) in the model group (117.65 ± 4.66 units/L) was significantly higher than those of the other three groups (P < 0.05). After treatment with 600 and 1200 mg of CPs/kg, the level of BALP decreased to 85.26 ± 7.35 and 97.03 ± 7.21 units/L, respectively. After treatment with 600 mg of CPs/kg, the bone calcium content significantly increased by 22% (femur) and 12.38% (tibia) compared to those of the model group. In addition, the bone mineral density in the 600 mg of CPs/kg group was significantly higher (femur, 0.37 ± 0.02 g/cm 2 ; tibia, 0.33 ± 0.02 g/cm 2 ) than in the model group (femur, 0.26 ± 0.01 g/cm 2 ; tibia, 0.23 ± 0.02 g/cm 2 ). The morphology results indicated bone structure improved after the treatment with CPs. Structural characterization demonstrated that Glu, Lys, and Arg play important roles in binding calcium and promoting calcium uptake. Our results indicated that CPs could promote calcium uptake and regulate bone formation.

A contact mechanics model for ankle implants with inclusion of surface roughness effects

NASA Astrophysics Data System (ADS)

Hodaei, M.; Farhang, K.; Maani, N.

2014-02-01

Total ankle replacement is recognized as one of the best procedures to treat painful arthritic ankles. Even though this method can relieve patients from pain and reproduce the physiological functions of the ankle, an improper design can cause an excessive amount of metal debris due to wear, causing toxicity in implant recipient. This paper develops a contact model to treat the interaction of tibia and talus implants in an ankle joint. The contact model describes the interaction of implant rough surfaces including both elastic and plastic deformations. In the model, the tibia and the talus surfaces are viewed as macroscopically conforming cylinders or conforming multi-cylinders containing micrometre-scale roughness. The derived equations relate contact force on the implant and the minimum mean surface separation of the rough surfaces. The force is expressed as a statistical integral function of asperity heights over the possible region of interaction of the roughness of the tibia and the talus implant surfaces. A closed-form approximate equation relating contact force and minimum separation is used to obtain energy loss per cycle in a load-unload sequence applied to the implant. In this way implant surface statistics are related to energy loss in the implant that is responsible for internal void formation and subsequent wear and its harmful toxicity to the implant recipient.

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.

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.

Biocompatibility testing of NiTi screws using immunohistochemistry on sections containing metallic implants.

PubMed

Berger-Gorbet, M; Broxup, B; Rivard, C; Yahia, L H

1996-10-01

NiTi is one of the most innovative concepts to have appeared in the field of metallic biomaterials in recent years but its biocompatibility remains controversial. We evaluated the biocompatibility of Nitinol screws using immunohistochemistry to observe the distribution of bone proteins during bone remodeling process around NiTi implant. Results were compared with screws made of Vitallium, c.p. titanium, Duplex austenitic-ferritic stainless steel (SAF), and Stainless Steel 316L. Screws were implanted in rabbit tibia for 3, 6, and 12 weeks. Embedding was performed in the hard resin Technovit, and for the immunohistochemical procedure undecalcified sections with bone-anchored implants could thus be used. The immunostaining method developed seemed to be a reliable technique to stain proteins in undecalcified sections. Biocompatibility results of the NiTi screws compared with the other screws showed a slower osteogenesis process characterized by no close contact between implant and bone, disorganized migration of osteoblasts around the implant, and a lower activity of osteonectin synthesis.

Mid-Infrared Spectroscopy Analysis of the Effects of Erbium, Chromium:Yattrium-Scandium-Gallium-Garnet (Er,Cr:YSGG) Laser Irradiation on Bone Mineral and Organic Components.

PubMed

Benetti, Carolina; Ana, Patricia Aparecida; Bachmann, Luciano; Zezell, Denise Maria

2015-12-01

The effects of varying the energy density of a high-intensity erbium, chromium: yttrium-scandium-gallium-garnet (Er,Cr:YSGG) laser on the mineral and organic components of bone tissue were evaluated using Fourier transform infrared spectroscopy. Bone samples obtained from the tibias of rabbits were irradiated with five energy densities (3, 6, 8, 12, and 15 J/cm(2)), and the effects on the carbonate to phosphate ratio and in the organic components were compared with those of nonirradiated samples. The increased temperature during the laser irradiation was also measured using infrared thermography to relate the observed spectral changes to the laser thermal effects. The analyses of the infrared spectra suggests that the irradiation with Er,Cr:YSGG promoted changes in bone tissue in both the mineral and organic components that depend on the laser energy density, pointing to the importance of using the proper energy density in clinical procedures.

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.

Tibial tunnel aperture irregularity after drilling with 5 reamer designs: a qualitative micro-computed tomography analysis.

PubMed

Geeslin, Andrew G; Jansson, Kyle S; Wijdicks, Coen A; Chapman, Mark A; Fok, Alex S; LaPrade, Robert F

2011-04-01

There is limited information in the literature on comparisons of antegrade versus retrograde reaming techniques and the effect on the creation of anterior cruciate ligament (ACL) tibial tunnel entry and exit apertures. Proximal and distal apertures of ACL tibial tunnels, as created with different reamers, will be affected by type of reamer design. Controlled laboratory study. Forty skeletally mature porcine tibias with bone mineral density values comparable with a young athletic population were included in this study. Five 9-mm reamer models were used (3 antegrade: A1, smooth-bore reamer; A2, acorn-head reamer; A3, flat-head reamer; 2 retrograde: R1, retrograde acorn reamer; R2, single-blade retrograde reamer), and a new reamer was used for each tibia (8 reamer-tibia pairs per reamer model). All specimens underwent micro-computed tomography scanning, and images were reconstructed and analyzed using 3-dimensional image analysis software. Aperture rim fractures were graded on a 0-IV scale that described the proportion of the fractured aperture circumference. Specimens with incomplete apertures were also recorded. Because of the unique characteristics of various tunnels, intratunnel characteristics were observed and recorded. In sum, 1 proximal and 7 distal aperture rim fractures were found; 3, 0, and 4 distal aperture rim fractures were found with groups A1, A2, and A3, respectively. Incomplete apertures were more commonly found at the distal aperture (n = 15) than the proximal aperture (n = 8); there were no tibias with this finding at both apertures. All incomplete distal apertures occurred with the retrograde technique, and all incomplete proximal apertures occurred with the antegrade technique, most commonly with reamer design A3. An added finding of tunnel curvature at the distal aspect of the tunnel was observed in all 8 tibias with R1 reamers and 5 tibias with R2 reamers. This phenomenon was not observed in any of the tibias reamed with the antegrade technique. Anterior cruciate ligament tibial tunnel aperture characteristics were highly dependent on reamer design. Optimal proximal aperture characteristics were produced by the retrograde reamers, whereas optimal distal aperture characteristics were obtained with the antegrade reamers. In addition, a phenomenon of tunnel curvature in retrograde-type reamers was found, which may have effects on ACL graft or screw fixation. Differences in tunnel aperture shapes and fractures depend on reamer design. This information is important for the creation of ACL reconstruction tunnels with different reamer designs.

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.

Biomechanical study of prophylactic internal fixation of the radial osteocutaneous donor site using the sheep tibia model.

PubMed

Avery, C M E; Best, A; Patterson, P; Rolton, J; Ponter, A R S

2007-09-01

This study investigated the strengthening effect of different types of plate and position after osteotomy of the sheep tibia, which is a model for the radial osteocutaneous donor site. Fifty matched pairs of adult sheep tibias were tested in torsion and four-point bending. Firstly, the weakening effect of an osteotomy was compared with the intact bone. Then pairs of bones with an osteotomy were compared with and without reinforcement with different types of 3.5mm plate. The plate was placed in either the anterior (over the defect) or posterior (on the intact cortex) position. In torsion the mean strength of the intact bone was 45% greater than after osteotomy (P=0.02). The reinforced bone was on average 61% stronger than the unreinforced bone (P<0.001). In bending the mean strength of the intact bone was 188% greater than after osteotomy (P=0.02). The reinforced bone was on average 184% stronger then the unreinforced bone (P<0.001). The tibia was able to withstand much greater loads in bending. The dynamic compression plate was the strongest reinforcement in both torsion and bending. The position of the plate did not alter the strengthening effect in torsion but the posterior position resisted greater bending loads (P=0.01). This may not be relevant in clinical practice as the radius is likely to fracture first as a result of lower torsional forces.

A Comparative 68Ga-Citrate and 68Ga-Chloride PET/CT Imaging of Staphylococcus aureus Osteomyelitis in the Rat Tibia

PubMed Central

Lankinen, Petteri; Noponen, Tommi; Autio, Anu; Luoto, Pauliina; Löyttyniemi, Eliisa; Hakanen, Antti J.

2018-01-01

There may be some differences in the in vivo behavior of 68Ga-chloride and 68Ga-citrate leading to different accumulation profiles. This study compared 68Ga-citrate and 68Ga-chloride PET/CT imaging under standardized experimental models. Methods. Diffuse Staphylococcus aureus tibial osteomyelitis and uncomplicated bone healing rat models were used (n = 32). Two weeks after surgery, PET/CT imaging was performed on consecutive days using 68Ga-citrate or 68Ga-chloride, and tissue accumulation was confirmed by ex vivo analysis. In addition, peripheral quantitative computed tomography and conventional radiography were performed. Osteomyelitis was verified by microbiological analysis and specimens were also processed for histomorphometry. Results. In PET/CT imaging, the SUVmax of 68Ga-chloride and 68Ga-citrate in the osteomyelitic tibias (3.6 ± 1.4 and 4.7 ± 1.5, resp.) were significantly higher (P = 0.0019 and P = 0.0020, resp.) than in the uncomplicated bone healing (2.7 ± 0.44 and 2.5 ± 0.49, resp.). In osteomyelitic tibias, the SUVmax of 68Ga-citrate was significantly higher than the uptake of 68Ga-chloride (P = 0.0017). In animals with uncomplicated bone healing, no difference in the SUVmax of 68Ga-chloride or 68Ga-citrate was seen in the operated tibias. Conclusions. This study further corroborates the use of 68Ga-citrate for PET imaging of osteomyelitis. PMID:29681785

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.

External fixation using locking plate in distal tibial fracture: a finite element analysis.

PubMed

Zhang, Jingwei; Ebraheim, Nabil; Li, Ming; He, Xianfeng; Schwind, Joshua; Liu, Jiayong; Zhu, Limei

2015-08-01

External fixation of tibial fractures using a locking plate has been reported with favorable results in some selected patients. However, the stability of external plate fixation in this fracture pattern has not been previously demonstrated. We investigated the stability of external plate fixation with different plate-bone distances. In this study, the computational processing model of external fixation of a distal tibial metaphyseal fracture utilizing the contralateral femoral less invasive stabilization system plate was analyzed. The plate was placed on the anteromedial aspect of tibia with different plate-bone distances: 1, 10, 20, and 30 mm. Under axial load, the stiffness of construct in all groups was higher than intact tibia. Under axial load with an internal rotational force, the stiffness of construct with 1 and 10 mm plate-bone distances was similar to that of an intact tibia and the stiffness of the construct with 20 and 30 mm distances was lower than that of an intact tibia. Under axial load with an external rotational force, the stiffness of the construct in all groups was lower than that of an intact tibia. The maximum plate stresses were concentrated at the two most distal screws and were highest in the construct with the 10 mm plate-bone distance, and least in the construct with a 1 mm plate-bone distance. To guarantee a stable external plate fixation in distal tibial fracture, the plate-bone distance should be less than 30 mm.

Joint angles of the ankle, knee, and hip and loading conditions during split squats.

PubMed

Schütz, Pascal; List, Renate; Zemp, Roland; Schellenberg, Florian; Taylor, William R; Lorenzetti, Silvio

2014-06-01

The aim of this study was to quantify how step length and the front tibia angle influence joint angles and loading conditions during the split squat exercise. Eleven subjects performed split squats with an additional load of 25% body weight applied using a barbell. Each subject's movements were recorded using a motion capture system, and the ground reaction force was measured under each foot. The joint angles and loading conditions were calculated using a cluster-based kinematic approach and inverse dynamics modeling respectively. Increases in the tibia angle resulted in a smaller range of motion (ROM) of the front knee and a larger ROM of the rear knee and hip. The external flexion moment in the front knee/hip and the external extension moment in the rear hip decreased as the tibia angle increased. The flexion moment in the rear knee increased as the tibia angle increased. The load distribution between the legs changed < 25% when split squat execution was varied. Our results describing the changes in joint angles and the resulting differences in the moments of the knee and hip will allow coaches and therapists to adapt the split squat exercise to the individual motion and load demands of athletes.

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

The Protective Effects of Exclusive Enteral Nutrition Formulas on Growth Factor Expression and the Proximal Tibial Epiphyseal Growth Plate in a TNBS-Induced IBD Rat Model.

PubMed

Shi, Jieru; Huang, Zhiheng; Wang, Yuhuan; Huang, Ying

2015-07-01

This study aimed to evaluate the effectiveness of different types of nutritional formulas in a rat model of TNBS-induced IBD. IBD was induced with TNBS in 4-week-old rats that were then fed different exclusive enteral nutrition diets for 7 days. The length of the tibia and the number of chondrocytes in the proximal tibias were analyzed at 7 days after supplementation. Immunohistochemical analysis, ELISA and real-time PCR were performed to evaluate the levels of growth hormone receptor (GHR) and insulin-like growth factor-I receptor (IGF-IR), the growth factors IGF-I and insulin-like growth factor-binding protein-3 (IGFBP3) , bone morphogenetic protein (BMP)-2 and BMP-6 respectively. The results demonstrated that the tibia length of the peptide formula group was longer than that of the IBD-Modulen(®) formula and normal diet groups (P < 0.05). Furthermore, the number of chondrocytes of the proximal tibial was more pronounced in the peptide formula group compared to the other groups (P < 0.05). The peptide formula was also more effective in increasing the expression of GHR compared to the other groups (P < 0.05), while the expression of IGF-IR was not significantly different (P > 0.05). In addition, the IGF-I and IGFBP3 levels were more pronounced in the peptide formula supplement group (P < 0.05), and the expression of BMP-2 and BMP-6 mRNA in the proximal tibia growth plate from the peptide formula group was higher than that in the ordinary formula and normal diet groups (P < 0.05). EEN, and particularly a peptide formula, exerted protective effects on the proximal tibial epiphyseal growth plate in a TNBS-induced IBD model.

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

Dietary non-phytate phosphorus requirement of broilers fed a conventional corn-soybean meal diet from 1 to 21 d of age.

PubMed

Liu, S B; Liao, X D; Lu, L; Li, S F; Wang, L; Zhang, L Y; Jiang, Y; Luo, X G

2017-01-01

An experiment was conducted to investigate the effect of dietary non-phytate phosphorus (NPP) level on growth performance, bone characteristics and phosphorus metabolism-related gene expressions, so as to evaluate the dietary NPP requirement of broiler chicks fed a conventional corn-soybean meal diet from 1 to 21 d of age. A total of 540 day-old Arbor Acres male chicks were randomly allocated to one of nine treatments with six replicate cages of 10 birds per cage in a completely randomized design, and fed a basal corn-soybean meal diet (containing 0.08% of NPP) supplemented with 0.10, 0.15, 0.25, 0.30, 0.35, 0.40, 0.45, or 0.50% of inorganic phosphorus in the form of CaHPO 4 ·2H 2 O, respectively. Each diet contained the constant calcium content of about 1.0%. The results showed that daily weight gain, serum inorganic P, tibia bone strength, tibia ash percentage, tibia bone mineral content (BMC) and density (BMD), middle toe ash percentage, middle toe BMC and BMD were affected (P < 0.0001) by dietary NPP level, and increased linearly (P < 0.0001) and quadraticly (P < 0.004) as dietary NPP levels increased. The gene expression of type IIb sodium-phosphate cotransporter (NaPi-IIb) in the duodenum was affected (P < 0.03) and decreased linearly (P < 0.002) as dietary NPP levels increased. Dietary NPP requirements estimated based on fitted broken-line models (P < 0.0001) of the sensitive indices including daily weight gain, tibia bone strength, tibia ash percentage, tibia BMC and BMD as well as middle toe ash percentage were 0.34∼0.39%. The results from this study indicate that tibia BMC and BMD might be new, sensitive, and noninvasive criteria to evaluate the dietary NPP requirements of broilers, and the dietary NPP requirement is 0.39% for broiler chicks fed a conventional corn-soybean meal diet from 1 to 21 d of age. © 2016 Poultry Science Association Inc.

Ricinus communis-based biopolymer and epidermal growth factor regulations on bone defect repair: A rat tibia model

NASA Astrophysics Data System (ADS)

Mendoza-Barrera, C.; Meléndez-Lira, M.; Altuzar, V.; Tomás, S. A.

2003-01-01

We report the effect of the addition of an epidermal growth factor to a Ricinus communis-based biopolymer in the healing of a rat tibia model. Bone repair and osteointegration after a period of three weeks were evaluated employing photoacoustic spectroscopy and x-ray diffraction. A parallel study was performed at 1, 2, 3, 4, 5, 6, 7, and 8 weeks with energy dispersive x-ray spectroscopy. We conclude that the use of an epidermal growth factor (group EGF) in vivo accelerates the process of bony repair in comparison with other groups, and that the employment of the Ricinus communis-based biopolymer as a bone substitute decreases bone production.

Inverse Dynamics Model for the Ankle Joint with Applications in Tibia Malleolus Fracture

NASA Astrophysics Data System (ADS)

Budescu, E.; Merticaru, E.; Chirazi, M.

The paper presents a biomechanical model of the ankle joint, in order to determine the force and the torque of reaction into the articulation, through inverse dynamic analysis, in various stages of the gait. Thus, knowing the acceleration of the foot and the reaction force between foot and ground during the gait, determined by experimental measurement, there was calculated, for five different positions of the foot, the joint reaction forces, on the basis of dynamic balance equations. The values numerically determined were compared with the admissible forces appearing in the technical systems of osteosynthesis of tibia malleolus fracture, in order to emphasize the motion restrictions during bone healing.

Compositional dependence of bioactivity of glasses in the system Na2O-K2O-MgO-CaO-B2O3-P2O5-SiO2.

PubMed

Brink, M; Turunen, T; Happonen, R P; Yli-Urpo, A

1997-10-01

The bioactivity, i.e., bone-bonding ability, of 26 glasses in the system Na2O-K2O-MgO-CaO-B2O3-P2O5-SiO2 was studied in vivo. This investigation of bioactivity was performed to establish the compositional dependence of bioactivity, and enabled a model to be developed that describes the relation between reactions in vivo and glass composition. Reactions in vivo were investigated by inserting glass implants into rabbit tibia for 8 weeks. The glasses and the surrounding tissue were examined using scanning electron microscopy (SEM), light microscopy, and energy-dispersive X-ray analysis (EDXA). For most of the glasses containing < 59 mol % SiO2, SEM and EDXA showed two distinct layers at the glass surface after implantation, one silica-rich and another containing calcium phosphate. The build-up of these layers in vivo was taken as a sign of bioactivity. The in vivo experiments showed that glasses in the investigated system are bioactive when they contain 14-30 mol % alkali oxides, 14-30 mol % alkaline earth oxides, and < 59 mol % SiO2. Glasses containing potassium and magnesium bonded to bone in a similar way as bioactive glasses developed so far.

Influence of controlled immediate loading and implant design on peri-implant bone formation.

PubMed

Vandamme, Katleen; Naert, Ignace; Geris, Liesbet; Vander Sloten, Jozef; Puers, Robert; Duyck, Joke

2007-02-01

Tissue formation at the implant interface is known to be sensitive to mechanical stimuli. The aim of the study was to compare the bone formation around immediately loaded versus unloaded implants in two different implant macro-designs. A repeated sampling bone chamber with a central implant was installed in the tibia of 10 rabbits. Highly controlled loading experiments were designed for a cylindrical (CL) and screw-shaped (SL) implant, while the unloaded screw-shaped (SU) implant served as a control. An F-statistic model with alpha=5% determined statistical significance. A significantly higher bone area fraction was observed for SL compared with SU (p<0.0001). The mineralized bone fraction was the highest for SL and significantly different from SU (p<0.0001). The chance that osteoid- and bone-to-implant contact occurred was the highest for SL and significantly different from SU (p<0.0001), but not from CL. When bone-to-implant contact was observed, a loading (SL versus SU: p=0.0049) as well as an implant geometry effect (SL versus CL: p=0.01) was found, in favour of the SL condition. Well-controlled immediate implant loading accelerates tissue mineralization at the interface. Adequate bone stimulation via mechanical coupling may account for the larger bone response around the screw-type implant compared with the cylindrical implant.

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.

Radiographic evidence of disuse osteoporosis in the monkey /M. nemestrina/

NASA Technical Reports Server (NTRS)

Young, D. R.; Schneider, V. S.

1981-01-01

Radiological techniques were utilized for monitoring progressive changes in compact bone in the tibia of monkeys during experimentally induced osteopenia. Bone mass loss in the tibia during restraint was evaluated from radiographs, from bone mineral analysis, and from images reconstructed from gamma ray computerized tomography. The losses during 6 months of restraint tended to occur predominantly in the proximal tibia and were characterized by subperiosteal bone loss, intracortical striations, and scalloped endosteal surfaces. Bone mineral content in the cross section of the tibia declined 17-21%. In 6 months of recovery, the mineral content of the proximal tibia remained depressed.

Kinematic repeatability of a multi-segment foot model for dance.

PubMed

Carter, Sarah L; Sato, Nahoko; Hopper, Luke S

2018-03-01

The purpose of this study was to determine the intra and inter-assessor repeatability of a modified Rizzoli Foot Model for analysing the foot kinematics of ballet dancers. Six university-level ballet dancers performed the movements; parallel stance, turnout plié, turnout stance, turnout rise and flex-point-flex. The three-dimensional (3D) position of individual reflective markers and marker triads was used to model the movement of the dancers' tibia, entire foot, hindfoot, midfoot, forefoot and hallux. Intra and inter-assessor reliability demonstrated excellent (ICC ≥ 0.75) repeatability for the first metatarsophalangeal joint in the sagittal plane. Intra-assessor reliability demonstrated excellent (ICC ≥ 0.75) repeatability during flex-point-flex across all inter-segmental angles except for the tibia-hindfoot and hindfoot-midfoot frontal planes. Inter-assessor repeatability ranged from poor to excellent (0.5 > ICC ≥ 0.75) for the 3D segment rotations. The most repeatable measure was the tibia-foot dorsiflexion/plantar flexion articulation whereas the least repeatable measure was the hindfoot-midfoot adduction/abduction articulation. The variation found in the inter-assessor results is likely due to inconsistencies in marker placement. This 3D dance specific multi-segment foot model provides insight into which kinematic measures can be reliably used to ascertain in vivo technical errors and/or biomechanical abnormalities in a dancer's foot motion.

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.

[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.

Outcomes of tibia shaft fractures caused by low energy gunshot wounds.

PubMed

Su, Charles A; Nguyen, Mai P; O'Donnell, Jeffrey A; Vallier, Heather A

2018-05-16

The purpose of this project was to compare the rates of infections, nonunions, malunions, and secondary operations in tibia fractures resultant from low energy GSWs versus those seen in open and closed tibia fractures resultant from blunt trauma. A secondary objective was to assess the utility of using the traditional Gustilo-Anderson classification system for open fractures to describe fractures secondary to low energy GSW. A retrospective review of 327 patients with tibia shaft fractures was conducted at our level I trauma center. Patients underwent a variety of interventions depending on their injury. Standard fixation techniques were utilized. Outcome measures include: mechanism of injury, rates of superficial and deep infection, nonunion, malunion, and secondary operations. Deep infection after low energy GSW tibia fractures was uncommon and seen in only 2.3% of patients. Rates of infection after low energy GSWs were similar to low and high energy closed tibia fractures resultant from blunt trauma, but significantly less than that seen in open type II (25%, p < 0.05), type IIIA (19.5%, p < 0.05), and type IIIB fractures (47%, p < 0.01). There were no nonunions following GSW fractures, versus 3.7% after closed tibia fractures from blunt trauma (p = 0.2). Nonunions were more common after open fractures from blunt trauma (11%, p < 0.05) versus GSWs. Differences in infection and nonunion were associated with more secondary operations (18%, p < 0.01) in the open tibia fracture group compared with GSWs (2.3%) and closed fractures (7.9% p = 0.19). While GSWs are traditionally thought of as open injuries, low energy GSW tibia fractures had a low rate of infection and no nonunions, and resulted in a reoperation rate similar to closed blunt tibia shaft fractures and significantly lower than open tibia fractures. Copyright © 2018. Published by Elsevier Ltd.

The anterior tilt angle of the proximal tibia epiphyseal plate: a significant radiological finding in young children with trampoline fractures.

PubMed

Stranzinger, Enno; Leidolt, Lars; Eich, Georg; Klimek, Peter Michael

2014-08-01

Evaluation of the anterior tilt angle of the proximal tibia epiphyseal plate in young children, which suffered a trampoline fracture in comparison with a normal population. 62 children (31 females, 31 males) between 2 and 5 years of age (average 2 years 11 months, standard deviation 11 months) with radiographs in two views of the tibia were included in this retrospective study. 25 children with proximal tibia fractures were injured with a history of jumping on a trampoline. All other causes for tibia fractures were excluded. A normal age-mapped control cohort of 37 children was compared. These children had neither evidence of a trampoline related injury nor a fracture of the tibia. The anterior tilt angle of the epiphyseal plate of the tibia was defined as an angle between the proximal tibia physis and the distal tibia physis on a lateral view. Two radiologists evaluated all radiographs for fractures and measured the anterior tilt angle in consensus. An unpaired Student's t-test was used for statistical analysis (SPSS). Original reports were reviewed and compared with the radiological findings and follow-up radiographs. In the normal control group, the average anterior tilt angle measured -3.2°, SD ± 2.8°. The children with trampoline fractures showed an anterior tilt of +4.4°, SD ± 2.9°. The difference was statistically significant, P<0.0001. In 6 patients (24% of all patients with confirmed fractures) the original report missed to diagnose the proximal tibial fracture. Young children between 2 and 5 years of age are at risk for proximal tibia fractures while jumping on a trampoline. These fractures may be very subtle and difficult to detect on initial radiographs. Measurement of the anterior tilt angle of the proximal tibia epiphyseal plate on lateral radiographs is supportive for interpreting correctly trampoline fractures. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Solving cross-disciplinary problems by mathematical modelling

NASA Astrophysics Data System (ADS)

Panfilov, D. A.; Romanchikov, V. V.; Krupin, K. N.

2018-03-01

The article deals with the creation of a human tibia 3D model by means of “Autodesk Revit-2016” PC based on tomogram data. The model was imported into “Lira- SAPR2013 R4” software system. To assess the possibility of education and the nature of bone fracture (and their visualization), the Finite Element Analysis (FEA) method was used. The geometric parameters of the BBK model corresponded to the physical parameters of the individual. The compact plate different thickness is modeled by rigidity properties of the finite elements in accordance with the parameters on the roentgenogram. The BBK model included parameters of the outer compact plate and the spongy substance having a more developed structure of the epiphysic region. In the “Lira-SAPR2013 R4” software system, mathematical modeling of the traumatic effect was carried out and the analysis of the stress-strain state of the finite element model of the tibia was made to assess fracture conditions.

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.

What are the important surgical factors affecting the wound healing after primary total knee arthroplasty?

PubMed

Harato, Kengo; Tanikawa, Hidenori; Morishige, Yutaro; Kaneda, Kazuya; Niki, Yasuo

2016-01-13

Wound condition after primary total knee arthroplasty (TKA) is an important issue to avoid any postoperative adverse events. Our purpose was to investigate and to clarify the important surgical factors affecting wound score after TKA. A total of 139 knees in 128 patients (mean 73 years) without severe comorbidity were enrolled in the present study. All primary unilateral or bilateral TKAs were done using the same skin incision line, measured resection technique, and wound closure technique using unidirectional barbed suture. In terms of the wound healing, Hollander Wound Evaluation Score (HWES) was assessed on postoperative day 14. We performed multiple regression analysis using stepwise method to identify the factors affecting HWES. Variables considered in the analysis were age, sex, body mass index (kg/m(2)), HbA1C (%), femorotibial angle (degrees) on plain radiographs, intraoperative patella eversion during the cutting phase of the femur and the tibia in knee flexion, intraoperative anterior translation of the tibia, patella resurfacing, surgical time (min), tourniquet time (min), length of skin incision (cm), postoperative drainage (ml), patellar height on postoperative lateral radiographs, and HWES. HWES was treated as a dependent variable, and others were as independent variables. The average HWES was 5.0 ± 0.8 point. According to stepwise forward regression test, patella eversion during the cutting phase of the femur and the tibia in knee flexion and anterior translation of the tibia were entered in this model, while other factors were not entered. Standardized partial regression coefficient was as follows: 0.57 in anterior translation of the tibia and 0.38 in patella eversion. Fortunately, in the present study using the unidirectional barbed suture, major wound healing problem did not occur. As to the surgical technique, intraoperative patella eversion and anterior translation of the tibia should be avoided for quality cosmesis in primary TKA.

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.

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

Bone augmentation for cancellous bone- development of a new animal model

PubMed Central

2013-01-01

Background Reproducible and suitable animal models are required for in vivo experiments to investigate new biodegradable and osteoinductive biomaterials for augmentation of bones at risk for osteoporotic fractures. Sheep have especially been used as a model for the human spine due to their size and similar bone metabolism. However, although sheep and human vertebral bodies have similar biomechanical characteristics, the shape of the vertebral bodies, the size of the transverse processes, and the different orientation of the facet joints of sheep are quite different from those of humans making the surgical approach complicated and unpredictable. Therefore, an adequate and safe animal model for bone augmentation was developed using a standardized femoral and tibia augmentation site in sheep. Methods The cancellous bone of the distal femur and proximal tibia were chosen as injection sites with the surgical approach via the medial aspects of the femoral condyle and proximal tibia metaphysis (n = 4 injection sites). For reproducible drilling and injection in a given direction and length, a custom-made c-shaped aiming device was designed. Exact positioning of the aiming device and needle positioning within the intertrabecular space of the intact bone could be validated in a predictable and standardized fashion using fluoroscopy. After sacrifice, bone cylinders (∅ 32 mm) were harvested throughout the tibia and femur by means of a diamond-coated core drill, which was especially developed to harvest the injected bone area exactly. Thereafter, the extracted bone cylinders were processed as non-decalcified specimens for μCT analysis, histomorphometry, histology, and fluorescence evaluation. Results The aiming device could be easily placed in 63 sheep and assured a reproducible, standardized injection area. In four sheep, cardiovascular complications occurred during surgery and pulmonary embolism was detected by computed tomography post surgery in all of these animals. The harvesting and evaluative methods assured a standardized analysis of all samples. Conclusions This experimental animal model provides an excellent basis for testing new biomaterials for their suitability as bone augmentation materials. Concomitantly, similar cardiovascular changes occur during vertebroplasties as in humans, thus making it a suitable animal model for studies related to vertebroplasty. PMID:23819858

Bone augmentation for cancellous bone- development of a new animal model.

PubMed

Klein, Karina; Zamparo, Enrico; Kronen, Peter W; Kämpf, Katharina; Makara, Mariano; Steffen, Thomas; von Rechenberg, Brigitte

2013-07-02

Reproducible and suitable animal models are required for in vivo experiments to investigate new biodegradable and osteoinductive biomaterials for augmentation of bones at risk for osteoporotic fractures. Sheep have especially been used as a model for the human spine due to their size and similar bone metabolism. However, although sheep and human vertebral bodies have similar biomechanical characteristics, the shape of the vertebral bodies, the size of the transverse processes, and the different orientation of the facet joints of sheep are quite different from those of humans making the surgical approach complicated and unpredictable. Therefore, an adequate and safe animal model for bone augmentation was developed using a standardized femoral and tibia augmentation site in sheep. The cancellous bone of the distal femur and proximal tibia were chosen as injection sites with the surgical approach via the medial aspects of the femoral condyle and proximal tibia metaphysis (n = 4 injection sites). For reproducible drilling and injection in a given direction and length, a custom-made c-shaped aiming device was designed. Exact positioning of the aiming device and needle positioning within the intertrabecular space of the intact bone could be validated in a predictable and standardized fashion using fluoroscopy. After sacrifice, bone cylinders (Ø 32 mm) were harvested throughout the tibia and femur by means of a diamond-coated core drill, which was especially developed to harvest the injected bone area exactly. Thereafter, the extracted bone cylinders were processed as non-decalcified specimens for μCT analysis, histomorphometry, histology, and fluorescence evaluation. The aiming device could be easily placed in 63 sheep and assured a reproducible, standardized injection area. In four sheep, cardiovascular complications occurred during surgery and pulmonary embolism was detected by computed tomography post surgery in all of these animals. The harvesting and evaluative methods assured a standardized analysis of all samples. This experimental animal model provides an excellent basis for testing new biomaterials for their suitability as bone augmentation materials. Concomitantly, similar cardiovascular changes occur during vertebroplasties as in humans, thus making it a suitable animal model for studies related to vertebroplasty.

[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.

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

Factors influencing interlocking screw failure in unreamed small diameter nails--a biomechanical study using a distal tibia fracture model.

PubMed

Weninger, Patrick; Schueller, Michael; Jamek, Michael; Stanzl-Tschegg, Stefanie; Redl, Heinz; Tschegg, Elmar K

2009-05-01

Unreamed tibia nails with small diameters are increasingly used for fracture fixation. However, little is known about the fatigue strength of proximal and distal interlocking screws in those nails. To date, no data are available reporting on mechanical differences of solid compared to cannulated tibial nails. The aim of this study was to assess the fatigue strength of proximal and distal interlocking screws of solid and cannulated small diameter tibia nails. We created a distal tibia fracture model (AO/OTA 43 A3) using 16 Sawbones. After fracture stabilization with one of four different nail types (Expert Tibial Nail, VersaNail, T2 Tibial Nailing System, Connex), mechanical testing was performed in three loading series (40,000 cycles each) with incremental loads. Timing and type of interlocking screw failure were assessed. Interlocking screw failure was observed significantly earlier (after a mean interval of 57,042 cycles) in cannulated tibial nails (VersaNail, T2) compared to solid nails (after a mean interval of 88,415 cycles; P < 0.001). Proximal interlocking screw failure was recorded if oblique screws were used proximally (VersaNail, T2, Connex). No distal interlocking screw failure was recorded in the Connex nail. Two- and three-part fractures of proximal or distal interlocking screws were observed in all specimen. Proximal and distal interlocking screw failure has to be considered in small diameter nails in case of delayed fracture healing. To support our results, further experimental studies and clinical series are necessary.

Bone-to-bone Fixation Enhances Functional Healing of the Porcine Anterior Cruciate Ligament Using a Collagen-Platelet Composite

PubMed Central

Murray, Martha M.; Magarian, Elise; Zurakowski, David; Fleming, Braden C.

2010-01-01

Purpose The purpose of this study was to determine if providing bony stabilization between the tibia and femur would improve the structural properties of an “enhanced” ACL repair using a collagen-platelet composite when compared to the traditional (Marshall) suture technique. Methods Twelve pigs underwent unilateral ACL transection and were treated with sutures connecting the bony femoral ACL attachment site to the distal ACL stump (LIGAMENT group), or to the tibia via a bone tunnel (TIBIA group). A collagen-platelet composite was placed around the sutures to enhance the biologic repair in both groups. Anteroposterior (AP) knee laxity and the graft structural properties were measured after 15 weeks of healing in both the ACL-repaired and contralateral ACL-intact joints. Results Enhanced ACL repair with bone-to-bone fixation significantly improved yield load and linear stiffness of the ACL repairs (p<0.05) after 15 weeks of healing. However, laxity values of the knees were similar in both groups of repaired knees (p>0.10). Conclusions Using an enhanced ACL suture repair technique that includes bone-to-bone fixation to protect the repair in the initial healing stages resulted in an ACL with improved structural properties after 15 weeks in the porcine model. Clinical Relevance The healing response of an ACL suture repair using a collagen-platelet composite can be enhanced by providing bony stabilization between the tibia and femur to protect the graft during the initial healing process in a translational model. PMID:20810092

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.

Accounting for spatial variation of trabecular anisotropy with subject-specific finite element modeling moderately improves predictions of local subchondral bone stiffness at the proximal tibia.

PubMed

Nazemi, S Majid; Kalajahi, S Mehrdad Hosseini; Cooper, David M L; Kontulainen, Saija A; Holdsworth, David W; Masri, Bassam A; Wilson, David R; Johnston, James D

2017-07-05

Previously, a finite element (FE) model of the proximal tibia was developed and validated against experimentally measured local subchondral stiffness. This model indicated modest predictions of stiffness (R 2 =0.77, normalized root mean squared error (RMSE%)=16.6%). Trabecular bone though was modeled with isotropic material properties despite its orthotropic anisotropy. The objective of this study was to identify the anisotropic FE modeling approach which best predicted (with largest explained variance and least amount of error) local subchondral bone stiffness at the proximal tibia. Local stiffness was measured at the subchondral surface of 13 medial/lateral tibial compartments using in situ macro indentation testing. An FE model of each specimen was generated assuming uniform anisotropy with 14 different combinations of cortical- and tibial-specific density-modulus relationships taken from the literature. Two FE models of each specimen were also generated which accounted for the spatial variation of trabecular bone anisotropy directly from clinical CT images using grey-level structure tensor and Cowin's fabric-elasticity equations. Stiffness was calculated using FE and compared to measured stiffness in terms of R 2 and RMSE%. The uniform anisotropic FE model explained 53-74% of the measured stiffness variance, with RMSE% ranging from 12.4 to 245.3%. The models which accounted for spatial variation of trabecular bone anisotropy predicted 76-79% of the variance in stiffness with RMSE% being 11.2-11.5%. Of the 16 evaluated finite element models in this study, the combination of Synder and Schneider (for cortical bone) and Cowin's fabric-elasticity equations (for trabecular bone) best predicted local subchondral bone stiffness. Copyright © 2017 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

Predictors of proximal tibia anterior shear force during a vertical stop-jump.

PubMed

Sell, Timothy C; Ferris, Cheryl M; Abt, John P; Tsai, Yung-Shen; Myers, Joseph B; Fu, Freddie H; Lephart, Scott M

2007-12-01

Anterior cruciate ligament (ACL) continues to be a significant medical issue for athletes participating in sports and recreational activities. Biomechanical analyses have determined that anterior shear force is the most direct loading mechanism of the ACL and a probable component of noncontact ACL injury. The purpose of this study was to examine the biomechanical predictors of proximal tibia anterior shear force during a stop-jump task. A biomechanical and electromyographic (EMG) analysis of the knee was conducted while subjects performed a vertical stop-jump task. The task was chosen to simulate an athletic maneuver that included a landing with a sharp deceleration and a change in direction. The final regression model indicated that posterior ground reaction force, external knee flexion moment, knee flexion angle, integrated EMG activity of the vastus lateralis, and sex (female) would significantly predict proximal tibia anterior shear force (p < 0.0001, R2 = 0.8609). Knee flexion moment had the greatest influence on proximal tibia anterior shear force. The mathematical relationships elucidated in the current study support previous clinical and basic science research examining noncontact ACL injuries. This data provides important evidence for clinicians who are examining the risk factors for these injuries and developing/validating training programs to reduce the incidence of injury. Copyright 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Natural tibialization of fibula in non-union tibia: Two cases.

PubMed

Prabhat, Vinay; Vargaonkar, Gauresh S; Mallojwar, Sunil R; Kumar, Ramesh

2016-01-01

Non-union of tibia is known to be a common complication after fracture both bones of leg treated conservatively. During the course of natural healing, fibula usually unites early as it had more soft tissue attachment and vascular supply. Due to early union of fibula and absence of axial force across the tibia, it undergoes non-union. Two cases, a 32-year-old male and 65-year-old female treated conservatively for fracture both bones of leg long years back, presented to us with mild calf pain on and off. On radiological examination, there was non-union of tibia along with compensatory fibular hypertrophy to the extent that fibula became main weight bearing bone. In both the cases, we observed gross fibular hypertrophy in presence of non-union of tibia. In conservatively treated cases of fracture, both bones of leg, non-union of tibia may coexist with compensatory hypertrophy of fibula to the extent that, it becomes main weight bearing bone of the leg. We are presenting here two cases of natural tibialization of fibula along with nonunion tibia. Our article supports the theory of Wolff's law.

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

[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.

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.

Mechanical vibration testing of a tibia in vivo and finite element analysis of the shank resonant properties

NASA Astrophysics Data System (ADS)

Maslov, Leonid B.

2003-10-01

Recent clinical studies clearly indicate that the resonant frequencies can be used to assess the healing state of a fractured long bone. Although these studies clearly show a certain relation between the resonant frequencies and the stiffness of the bone, the nature of this relation has not yet studied very well. The attempt of considering the locomotion system of a human shank in complex is firstly presented in this paper. The finite element model of the soft and hard tissues composed of the human shank is developed and the vibration numerical analysis is performed. The values of the resonant frequencies for the isolated tibia and for the complex biomechanical system formed by tibia, fibula, achilles tendon and principal shank muscles are obtained during finite element analysis. The obtained result can be used as theoretical fundament to developing low-frequency resonant methods for testing and diagnostics of the physiological conditions of soft and hard tissue during medical treatment and rehabilitation time period after surgery operation.

Load transfer in the proximal tibia following implantation with a unicompartmental knee replacement: a static snapshot.

PubMed

Simpson, D J; Kendrick, B J L; Dodd, C A F; Price, A J; Gill, H S; Murray, D W

2011-05-01

Unicompartmental knee replacement (UKR) is an appealing alternative to total knee replacement when the patient has isolated medial compartment osteoarthritis. A common observation post-operatively is radiolucency between the tibial tray wall and the bone. In addition, some patients complain of persistent pain over the proximal tibia antero-medially; this may be related to elevated bone strains in the tibia. Currently, there is no intentionally made mechanical bond between the vertical wall of an Oxford UKR and the adjacent bone; whether one exists or not will influence the load transmission in the proximal tibia and may affect the elevated tibia strain. The aim of this study was to investigate how introducing a mechanical tie between the tibial tray wall and the adjacent bone might alter the load carried into the tibia for both cemented and cementless UKRs. Strain energy density in the region of bone adjacent to the tray wall was considerably increased when a mechanical tie was introduced; this has the potential of reducing the likelihood of a radiolucency occurring in that region. Moreover, a mechanical tie had the effect of reducing proximal tibia strain, which may decrease the incidence of pain following implantation with a UKR.

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.

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.

Associations among slipped capital femoral epiphysis, tibia vara, and type 2 juvenile diabetes.

PubMed

Bowen, James Richard; Assis, Morcello; Sinha, Kumar; Hassink, Sandra; Littleton, Aaron

2009-06-01

Clinical consequences of obesity are numerous and include slipped capital epiphysis of the femur, tibia vara, impaired mobility, insufficient muscle strength, glucose intolerance, type 2 diabetes, hyperlipidemia, nonalcoholic fatty liver disease, cholelithiasis, hypertension, sleep apnea, polycystic ovary disease, increased cardiorespiratory effort, and pseudotumor cerebri, among others. Because slipped capital femoral epiphysis, tibia vara, and type 2 diabetes are observed commonly in obese children, a degree of multiple disease occurrence in a patient would be anticipated; however, the senior author has never observed an obese adolescent who presented at the initial diagnosis with a coexistence of slipped capital femora epiphysis, tibia vara, or type 2 diabetes, so, possibly, these constellations of comorbidities may represent unique obesity phenotypes. We reviewed the population consisting of all consecutive patients with newly diagnosed slipped capital femoral epiphysis or tibia vara from 2000 to 2006 and a selected group of patients with type 2 diabetes treated at the Alfred I. duPont Hospital for Children, Wilmington, DE. There were 57 cases of slipped capital femoral epiphysis, 41 cases of tibia vara, and 53 cases of type 2 diabetes. The tibia vara group had the highest body mass index (BMI; 40.81 [13.01]); the diabetes group (BMI, 35.76 [7.04]) and the slipped capital femoral epiphysis group (BMI, 29.08 [7.07]) had the lowest BMI. There was no significant difference in age at the disease onset and height between groups. There was no overlap of disease at initial presentation among slipped capital femoral epiphysis, adolescent tibia vara, and type 2 diabetes. We observed 3 separate obesity-related phenotypes in adolescents with no overlap of disease at initial presentation among slipped capital femoral epiphysis, adolescent tibia vara, and type 2 diabetes.

[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.

Age-related changes in bone strength from HR-pQCT derived microarchitectural parameters with an emphasis on the role of cortical porosity.

PubMed

Vilayphiou, Nicolas; Boutroy, Stephanie; Sornay-Rendu, Elisabeth; Van Rietbergen, Bert; Chapurlat, Roland

2016-02-01

The high resolution peripheral computed tomography (HR-pQCT) technique has seen recent developments with regard to the assessment of cortical porosity. In this study, we investigated the role of cortical porosity on bone strength in a large cohort of women. The distal radius and distal tibia were scanned by HR-pQCT. We assessed bone strength by estimating the failure load by microfinite element analysis (μFEA), with isotropic and homogeneous material properties. We built a multivariate model to predict it, using a few microarchitecture variables including cortical porosity. Among 857 Caucasian women analyzed with μFEA, we found that cortical and trabecular properties, along with the failure load, impaired slightly with advancing age in premenopausal women, the correlations with age being modest, with |rage| ranging from 0.14 to 0.38. After the onset of the menopause, those relationships with age were stronger for most parameters at both sites, with |rage| ranging from 0.10 to 0.64, notably for cortical porosity and failure load, which were markedly deteriorated with increasing age. Our multivariate model using microarchitecture parameters revealed that cortical porosity played a significant role in bone strength prediction, with semipartial r(2)=0.22 only at the tibia in postmenopausal women. In conclusion, in our large cohort of women, we observed a small decline of bone strength at the tibia before the onset of menopause. We also found an age-related increase of cortical porosity at both scanned sites in premenopausal women. In postmenopausal women, the relatively high increase of cortical porosity accounted for the decline in bone strength only at the tibia. Copyright © 2015 Elsevier Inc. All rights reserved.

Tubular space truss structure for SKITTER 2 robot

NASA Technical Reports Server (NTRS)

Beecham, Richard; Dejulio, Linda; Delorme, Paul; Eck, Eric; Levy, Avi; Lowery, Joel; Radack, Joe; Sheffield, Randy; Stevens, Scott

1988-01-01

The Skitter 2 is a three legged transport vehicle designed to demonstrate the principle of a tripod walker in a multitude of environments. The tubular truss model of Skitter 2 is a proof of principal design. The model will replicate the operational capabilities of Skitter 2 including its ability to self-right itself. The project's focus was on the use of light weight tubular members in the final structural design. A strong design for the body was required as it will undergo the most intense loading. Triangular geometry was used extensively in the body, providing the required structural integrity and eliminating the need for cumbersome shear panels. Both the basic femur and tibia designs also relied on the strong geometry of the triangle. An intense literature search aided in the development of the most suitable weld techniques, joints, linkages, and materials required for a durable design. The hinge design features the use of spherical rod end bearings. In order to obtain a greater range of mobility in the tibia, a four-bar linkage was designed which attaches both to the femur and the tibia. All component designs, specifically the body, femur, and the tibia were optimized using the software package IDEAS 3.8A Supertab. The package provided essential deformation and stress analysis information on each component's design. The final structure incurred only a 0.0544 inch deflection in a maximum (worst case) loading situation. The highest stress experienced by any AL6061-T6 tubular member was 1920 psi. The structural integrity of the final design facilitated the use of Aluminum 6061-T6 tubing. The tubular truss structure of Skitter 2 is an effective and highly durable design. All facets of the design are structurally sound and cost effective.

Onset of mandible and tibia osteoradionecrosis – a comparative pilot study in the rat

PubMed Central

Damek-Poprawa, Monika; Both, Stefan; Wright, Alexander C.; Maity, Amit; Akintoye, Sunday O.

2012-01-01

Objectives Osteoradionecrosis (ORN) is common in the jaws following radiotherapy. We hypothesized that mandible is more susceptible to ORN than tibia based on site-disparity in hypoxic-hypocellular-hypovascular tissue breakdown. Study Design Twelve rats received 50 Gy irradiation to mandible or tibia; 4 of 12 rats further received minor surgical trauma to the irradiated sites. Structural and cellular skeletal changes were assessed with computer tomography, histology and immunostaining. Results Mandible developed ORN with 70% mean bone loss 10 weeks post-irradiation (p < 0.05) while tibia was structurally and radiological intact for 20 weeks post-irradiation. Hypocellularity, hypoxia and oxidative stress were higher in irradiated mandible (p < 0.001) than tibia (p < 0.01) but vascular damage was similar at both skeletal sites. Combined effects of radiation and minor trauma promoted mandibular alveolar bone loss and tibial fracture Conclusion ORN has a more rapid onset in mandible relative to tibia in the rat PMID:23254371

Novel Osteogenic Ti-6Al-4V Device For Restoration Of Dental Function In Patients With Large Bone Deficiencies: Design, Development And Implementation

PubMed Central

Cohen, D. J.; Cheng, A.; Kahn, A.; Aviram, M.; Whitehead, A. J.; Hyzy, S. L.; Clohessy, R. M.; Boyan, B. D.; Schwartz, Z.

2016-01-01

Custom devices supporting bone regeneration and implant placement are needed for edentulous patients with large mandibular deficiencies where endosteal implantation is not possible. We developed a novel subperiosteal titanium-aluminum-vanadium bone onlay device produced by additive manufacturing (AM) and post-fabrication osteogenic micro-/nano-scale surface texture modification. Human osteoblasts produced osteogenic and angiogenic factors when grown on laser-sintered nano-/micro-textured surfaces compared to smooth surfaces. Surface-processed constructs caused higher bone-to-implant contact, vertical bone growth into disk pores (microCT and histomorphometry), and mechanical pull-out force at 5 and 10 w on rat calvaria compared to non surface-modified constructs, even when pre-treating the bone to stimulate osteogenesis. Surface-modified wrap-implants placed around rabbit tibias osseointegrated by 6 w. Finally, patient-specific constructs designed to support dental implants produced via AM and surface-processing were implanted on edentulous mandibular bone. 3 and 8 month post-operative images showed new bone formation and osseointegration of the device and indicated stability of the dental implants. PMID:26854193

Novel Osteogenic Ti-6Al-4V Device For Restoration Of Dental Function In Patients With Large Bone Deficiencies: Design, Development And Implementation.

PubMed

Cohen, D J; Cheng, A; Kahn, A; Aviram, M; Whitehead, A J; Hyzy, S L; Clohessy, R M; Boyan, B D; Schwartz, Z

2016-02-08

Custom devices supporting bone regeneration and implant placement are needed for edentulous patients with large mandibular deficiencies where endosteal implantation is not possible. We developed a novel subperiosteal titanium-aluminum-vanadium bone onlay device produced by additive manufacturing (AM) and post-fabrication osteogenic micro-/nano-scale surface texture modification. Human osteoblasts produced osteogenic and angiogenic factors when grown on laser-sintered nano-/micro-textured surfaces compared to smooth surfaces. Surface-processed constructs caused higher bone-to-implant contact, vertical bone growth into disk pores (microCT and histomorphometry), and mechanical pull-out force at 5 and 10 w on rat calvaria compared to non surface-modified constructs, even when pre-treating the bone to stimulate osteogenesis. Surface-modified wrap-implants placed around rabbit tibias osseointegrated by 6 w. Finally, patient-specific constructs designed to support dental implants produced via AM and surface-processing were implanted on edentulous mandibular bone. 3 and 8 month post-operative images showed new bone formation and osseointegration of the device and indicated stability of the dental implants.

New approach in evaluation of ceramic-polymer composite bioactivity and biocompatibility.

PubMed

Borkowski, Leszek; Sroka-Bartnicka, Anna; Polkowska, Izabela; Pawlowska, Marta; Palka, Krzysztof; Zieba, Emil; Slosarczyk, Anna; Jozwiak, Krzysztof; Ginalska, Grazyna

2017-09-01

Regeneration of bone defects was promoted by a novel β-glucan/carbonate hydroxyapatite composite and characterized by Raman spectroscopy, microCT and electron microscopy. The elastic biomaterial with an apatite-forming ability was developed for bone tissue engineering and implanted into the critical-size defects of rabbits' tibiae. The bone repair process was analyzed on non-decalcified bone/implant sections during a 6-month regeneration period. Using spectroscopic methods, we were able to determine the presence of amides, lipids and assign the areas of newly formed bone tissue. Raman spectroscopy was also used to assess the chemical changes in the composite before and after the implantation process. SEM analyses showed the mineralization degree in the defect area and that the gap size decreased significantly. Microscopic images revealed that the implant debris were interconnected to the poorly mineralized inner side of a new bone tissue. Our study demonstrated that the composite may serve as a biocompatible background for collagen ingrowth and exhibits the advantages of applying Raman spectroscopy, SEM and microCT in studying these samples.

Basic research and clinical application of beta-tricalcium phosphate (β-TCP).

PubMed

Tanaka, T; Komaki, H; Chazono, M; Kitasato, S; Kakuta, A; Akiyama, S; Marumo, K

2017-09-01

The mechanism of bone substitute resorption involves two processes: solution-mediated and cell-mediated disintegration. In our previous animal studies, the main resorption process of beta-tricalcium phosphate (β-TCP) was considered to be cell-mediated disintegration by TRAP-positive cells. Thus, osteoclast-mediated resorption of β-TCP is important for enabling bone formation. We also report the results of treatment with β-TCP graft in patients since 1989. Two to three weeks after implantation, resorption of β-TCP occurred from the periphery, and then continued toward the center over time. Complete or nearly complete bone healing was achieved in most cases within a few years and was dependent upon the amount of implanted material, the patient's age, and the type of bone (cortical or cancellous). We have previously reported that an injectable complex of β-TCP granules and collagen supplemented with rhFGF-2 enabled cortical bone regeneration of rabbit tibiae. Based on the experimental results, we applied this technique to the patients with femoral and humeral fractures in elderly patients, and obtained bone union. Copyright © 2017 Elsevier Masson SAS. 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.

Longitudinal changes in bone lead levels: the VA Normative Aging Study.

PubMed

Wilker, Elissa; Korrick, Susan; Nie, Linda H; Sparrow, David; Vokonas, Pantel; Coull, Brent; Wright, Robert O; Schwartz, Joel; Hu, Howard

2011-08-01

Bone lead is a cumulative measure of lead exposure that can also be remobilized. We examined repeated measures of bone lead over 11 years to characterize long-term changes and identify predictors of tibia and patella lead stores in an elderly male population. Lead was measured every 3 to 5 years by k-x-ray fluorescence and mixed-effect models with random effects were used to evaluate change over time. A total of 554 participants provided up to four bone lead measurements. Final models predicted a -1.4% annual decline (95% CI: -2.2 to -0.7) for tibia lead and piecewise linear model for patella with an initial decline of 5.1% per year (95% CI: -6.2 to -3.9) during the first 4.6 years but no significant change thereafter (-0.4% [95% CI: -2.4 to 1.7]). These results suggest that bone lead half-life may be longer than previously reported.

Evolution of bone microanatomy of the tetrapod tibia and its use in palaeobiological inference.

PubMed

Kriloff, A; Germain, D; Canoville, A; Vincent, P; Sache, M; Laurin, M

2008-05-01

Bone microanatomy appears to track changes in various physiological or ecological properties of the individual or the taxon. Analyses of sections of the tibia of 99 taxa show a highly significant (P

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

The effects of subcutaneous injection of nicotine on osseointegration of machined and anodized implants in rabbits.

PubMed

Linden, Maria Salete Sandini; Bittencourt, Marcos Eugênio de; Carli, João Paulo De; Miyagaki, Daniela Cristina; Santos, Pâmela Letícia Dos; Paranhos, Luiz Renato; Groppo, Francisco Carlos; Ramacciato, Juliana Cama

2018-01-01

To evaluate the influence of subcutaneous injection nicotine in osseointegration process on different implant surfaces. Twenty-two male rabbits were distributed into two groups according to the subcutaneous injections: (1) nicotine 3 mg/day/kg and (2) 0.9 % NaCI 3 mL/day/kg, three times a day; subgroups were then designated-machined and anodized implants were placed in the right and left tibia bones, respectively. The animals were submitted euthanasia after periods of eight weeks to determine nicotine and cotinine levels, alkaline phosphatase and biomechanical analysis. The plasmatic levels of nicotine and cotinine were 0.5 ± 0.28 ng/mL and 9.5 ± 6.51 ng/mL, respectively. The alkaline phosphatase analyses in blood levels in control group were observed 40.8 ± 11.88 UI/L and 40.75 ± 12.46 UI/L, for the surfaces machined and anodized, respectively. In the test group was observed levels 37.9 ± 4.84 UI/L, for both implant surfaces. No significant differences were observed between control and test groups and between the implant surfaces regarding alkaline phosphatase blood levels. For biomechanics, no significant differences were observed in control group between the machined (25±8.46 Ncm) or anodized (31.2 ± 6.76 Ncm) implants. However, the treatment with nicotine induced higher torque than control in both machined (38.3 ± 13.52 Ncm) and anodized (35.5 ± 14.17 Ncm) implants, with p = 0.0024 and p = 0.0121, respectively. Subcutaneous injection of nicotine following implant insertion didn't have effect on osseointegration, independently from the implant surface.

Magnesium release from mesoporous carriers on endosseus implants does not influence bone maturation at 6 weeks in rabbit bone.

PubMed

Galli, Silvia; Andersson, Martin; Jinno, Yohei; Karlsson, Johan; He, Wenxiao; Xue, Ying; Mustafa, Kamal; Wennerberg, Ann; Jimbo, Ryo

2017-10-01

The release of magnesium ions (Mg 2+ ) from titanium surfaces has been shown to boost the initial biological response of peri-implant bone and to increase the biomechanical strength of osseointegration. The objective of the present paper was to investigate if the initial improvement in osseointegration would influence the bone remodeling also during the maturation stage of bone healing. Titanium implants were coated with mesoporous titania layers and either loaded with Mg 2+ (test group) or left untreated (control group). The implants were inserted in the tibiae of 10 New Zealand White rabbits. Osseointegration was assessed after 6 weeks by means of biomechanical testing (RTQ), non-decalcified histology and histomorphometry (BIC%, BA%, NBA%). The expression of genes involved in the bone formation and remodeling was quantified using qPCR. Mg 2+ releasing mesoporous titania coatings showed, on average, higher removal torques and histomorphometrical outcomes (RTQ: 17.2 Ncm vs. 15 Ncm; BIC: 38.8% vs. 32.1%; BA%: 71.6% vs. 64%; NBA% 62.5% vs. 54% for the tests vs the controls); however, the differences were not statistically significant. Three osteogenic markers, osteocalcin (OC), collagen 1 alpha 1 (COL1A1), and alkalin phosphatase (ALPL), were respectively 2-fold, 1.53-fold, and 1.13-fold up-regulated in the control group compared to the test. The expression of COL1A1 was particularly high in both groups, while the biomarkers for remodeling and inflammation showed a low expression in both groups. The results suggested that the initial enhancement in osseointegration induced by magnesium release from mesoporous titania coatings has no detrimental effects during bone maturation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2118-2125, 2017. © 2016 Wiley Periodicals, Inc.

Percutaneous external fixator pins with bactericidal micron-thin sol-gel films for the prevention of pin tract infection.

PubMed

Qu, Haibo; Knabe, Christine; Radin, Shula; Garino, Jonathan; Ducheyne, Paul

2015-09-01

Risk of infection is considerable in open fractures, especially when fracture fixation devices are used to stabilize the fractured bones. Overall deep infection rates of 16.2% have been reported. The infection rate is even greater, up to 32.2%, with external fixation of femoral fractures. The use of percutaneous implants for certain clinical applications, such as percutaneous implants for external fracture fixation, still represents a challenge today. Currently, bone infections are very difficult to treat. Very potent antibiotics are needed, which creates the risk of irreversible damage to other organs, when the antibiotics are administered systemically. As such, controlled, local release is being pursued, but no such treatments are in clinical use. Herein, the use of bactericidal micron-thin sol-gel films on metallic fracture fixation pins is reported. The data demonstrates that triclosan (2,4,4'-trichloro-2'-hydroxydiphenylether), an antimicrobial agent, can be successfully incorporated into micron-thin sol-gel films deposited on percutaneous pins. The sol-gel films continuously release triclosan in vitro for durations exceeding 8 weeks (longest measured time point). The bactericidal effect of the micron-thin sol-gel films follows from both in vitro and in vivo studies. Inserting percutaneous pins in distal rabbit tibiae, there were no signs of infection around implants coated with a micron-thin sol-gel/triclosan film. Healing had progressed normally, bone tissue growth was normal and there was no epithelial downgrowth. This result was in contrast with the results in rabbits that received control, uncoated percutaneous pins, in which abundant signs of infection and epithelial downgrowth were observed. Thus, well-adherent, micron-thin sol-gel films laden with a bactericidal molecule successfully prevented pin tract infection. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

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.

Simulation of Anterior Cruciate Ligament Deficiency in a Musculoskeletal Model with Anatomical Knees

PubMed Central

Guess, Trent M; Stylianou, Antonis

2012-01-01

Abnormal knee kinematics and meniscus injury resulting from anterior cruciate ligament (ACL) deficiency are often implicated in joint degeneration even though changes in tibio-femoral contact location after injury are small, typically only a few millimeters. Ligament reconstruction surgery does not significantly reduce the incidence of early onset osteoarthritis. Increased knowledge of knee contact mechanics would increase our understanding of the effects of ACL injury and help guide ACL reconstruction methods. Presented here is a cadaver specific computational knee model combined with a body-level musculoskeletal model from a subject of similar height and weight as the cadaver donor. The knee model was developed in the multi-body framework and includes representation of the menisci. Experimental body-level measurements provided input to the musculoskeletal model. The location of tibio-menisco-femoral contact as well as contact pressures were compared for models with an intact ACL, partial ACL transection (posterolateral bundle transection), and full ACL transection during a muscle driven forward dynamics simulation of a dual limb squat. During the squat, small changes in femur motion relative to the tibia for both partial and full ACL transection push the lateral meniscus in the posterior direction at extension. The central-anterior region of the lateral meniscus then becomes “wedged” between the tibia and femur during knee flexion. This “wedging” effect does not occur for the intact knee. Peak contact pressure and contact locations are similar for the partial tear and complete ACL transection during the deep flexion portion of the squat, particularly on the lateral side. The tibio-femoral contact location on the tibia plateau shifts slightly to the posterior and lateral direction with ACL transection. PMID:22470411

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...

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

Regional bone geometry of the tibia in triathletes and stress reactions--an observational study.

PubMed

Newsham-West, Richard J; Lyons, Brett; Milburn, Peter D

2014-03-01

The association between tibial morphology and tibial stress fractures or tibial stress syndrome was examined in triathletes with an unusually high incidence of these injuries. A cross-sectional study design examined associations between tibial geometry from MRI images and training and injury data between male and female triathletes and between stress fracture (SF) and non-stress fracture (NSF) groups. Fifteen athletes (7 females, 8 males) aged 17-23 years who were currently able to train and race were recruited from the New Zealand Triathlete Elite Development Squad. Geometric measurements were taken at 5 zones along the tibia using MRI and compared between symptomatic and asymptomatic tibiae subjects. SF tibiae displayed either oedema within the cancellous bone and/or stress fracture on MRI. When collapsed across levels, symptomatic tibiae had thicker medial cortices (F1,140=9.285, p=0.003), thicker lateral cortices (F1,140=10.129, p=0.002) and thinner anterior cortices (F1,140=14.517, p=0.000) than NSF tibiae. Only medial cortex thickness in SF tibia was significantly different (F4,140=3.358, p=0.012) at different levels. Follow-up analysis showed that athletes showing oedema within the cancellous bone and/or stress fracture on MRI had, within 2 years of analysis, subsequently taken time off training and racing due a tibial stress fracture. The thinner anterior cortex in SF tibiae is associated with a stress reaction in these triathletes. Copyright © 2013 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

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.

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.

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.

[CHANGES OF SEMAPHORIN 3A EXPRESSION IN HEALING OF TIBIA FRACTURE AFTER TRAUMATIC BRAIN INJURY].

PubMed

Li, Zhengzheng; Zhao, Junwei; Yi, Zhigang; Luo, Wei; Li, Kang; Wang, Yuliang; Wang, Jing; An, Liping; Ma, Jinglin

2016-10-08

To investigate the mechanism of Semaphorin 3A (Sema3A) in fracture healing after nerve injury by observing the expression of Sema3A in the tibia fracture healing after traumatic brain injury (TBI). A total of 192 Wistar female rats, 8-10 weeks old and weighing 220-250 g, were randomly divided into tibia fracture group (group A, n =48), TBI group (group B, n =48), TBI with tibia fracture group (group C, n =48), and control group (group D, n =48). The tibia fracture model was established at the right side of group A; TBI model was made in group B by the improved Feeney method; the TBI and tibia fracture model was made in group C; no treatment was given in group D. The tissue samples were respectively collected at 3, 5, 7, 14, 21, and 28 days after operation; HE staining, immunohistochemistry staining, and Western blot method were used for the location and quantitative detection of Sema3A in callus tissue. HE staining showed that no obvious changes were observed at each time point in groups B and D. At 3 and 5 days, there was no obvious callus growth at fracture site with inflammatory cells and fibrous tissue filling in groups A and C. At 7 and 14 days, fibrous tissue grew from periosteum to fracture site in groups A and C; the proliferation of chondrocytes in exterior periosteum gradually formed osteoid callus at fracture site in groups A and C. The chondrocyte had bigger size, looser arrangement, and more osteoid in group C than group A. Group B had disorder periosteum, slight subperiosteal bone hyperplasia, and no obvious change of bone trabecula in group B when compared with group D. At 21 and 28 days, cartilage callus was gradually replaced by new bone trabecula in groups A and C. Group C had loose arrange, disorder structure, and low density of bone trabecula, big callus area and few chondrocyte and osteoid when compared with group A; group B was similar to Group D. Immunohistochemistry staining showed that Sema3A expression in chondrocytes in group C was higher than that in group A, particularly at 7, 14, and 21 day. Sema3A was significantly higher in osteoblasts of new bone trabecula in group A than group C, especially at 14 and 21 days ( P <0.05). Western blot results showed that the Sema3A had the same expression trend during fracture healing in groups A and C. However, the expression of Sema3A protein was significantly higher in group C than group A ( P <0.05) and in group B than group D ( P <0.05) at 7, 14, 21, and 28 days. Abnormal expression of Sema3A may play a role in fracture healing after nerve injury by promoting the chondrocytes proliferation and reducing the distribution of sensory nerve fibers and osteoblast differentiation.

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.

Fixation of a split fracture of the lateral tibial plateau with a locking screw plate instead of cannulated screws would allow early weight bearing: a computational exploration.

PubMed

Carrera, Ion; Gelber, Pablo Eduardo; Chary, Gaetan; González-Ballester, Miguel A; Monllau, Juan Carlos; Noailly, Jerome

2016-10-01

To assess, with finite element (FE) calculations, whether immediate weight bearing would be possible after surgical stabilization either with cannulated screws or with a locking plate in a split fracture of the lateral tibial plateau (LTP). A split fracture of the LTP was recreated in a FE model of a human tibia. A three-dimensional FE model geometry of a human femur-tibia system was obtained from the VAKHUM project database, and was built from CT images from a subject with normal bone morphologies and normal alignment. The mesh of the tibia was reconverted into a geometry of NURBS surfaces. A split fracture of the lateral tibial plateau was reproduced by using geometrical data from patient radiographs. A locking screw plate (LP) and a cannulated screw (CS) systems were modelled to virtually reduce the fracture and 80 kg static body-weight was simulated. While the simulated body-weight led to clinically acceptable interfragmentary motion, possible traumatic bone shear stresses were predicted nearby the cannulated screws. With a maximum estimation of about 1.7 MPa maximum bone shear stresses, the Polyax system might ensure more reasonable safety margins. Split fractures of the LTP fixed either with locking screw plate or cannulated screws showed no clinically relevant IFM in a FE model. The locking screw plate showed higher mechanical stability than cannulated screw fixation. The locking screw plate might also allow full or at least partial weight bearing under static posture at time zero.

Low Preoperative BMD Is Related to High Migration of Tibia Components in Uncemented TKA-92 Patients in a Combined DEXA and RSA Study With 2-Year Follow-Up.

PubMed

Andersen, Mikkel R; Winther, Nikkolaj S; Lind, Thomas; Schrøder, Henrik M; Flivik, Gunnar; Petersen, Michael M

2017-07-01

The fixation of uncemented tibia components in total knee arthroplasty may rely on the bone quality of the tibia; however, no previous studies have shown convincing objective proof of this. Component migration is relevant as it has been shown to predict aseptic loosening. We performed 2-year follow-up of 92 patients who underwent total knee arthroplasty surgery with an uncemented tibia component. Bone mineral density (BMD; g/cm 2 ) of the tibia host bone was measured preoperatively using dual energy X-ray absorptiometry. The proximal tibia was divided into 2 regions of interest (ROI) in the part of the tibia bone where the components were implanted. Radiostereometric analysis was performed postoperatively and after 3, 6, 12, and 24 months. The primary outcome was maximum total point motion (MTPM; mm). Regression analysis was performed to evaluate the relation between preoperative BMD and MTPM. We found low preoperative BMD in ROI1 to be significantly related to high MTPM at all follow-ups: after 3 months (R 2  = 20%, P BMD  = 0.017), 6 months (R 2  = 29%, P BMD  = 0.003), 12 months (R 2  = 33%, P BMD  = 0.001), and 24 months (R 2  = 27%, P BMD  = 0.001). We also found a significant relation for low BMD in ROI2 and high MTPM: 3 months (R 2  = 19%, P BMD  = 0.042), 6 months (R 2  = 28%, P BMD  = 0.04), 12 months (R 2  = 32%, P BMD  = 0.004), and 24 months (R 2  = 24%, P BMD  = 0.005). Low preoperative BMD in the tibia is related to high MTPM. Thus, high migration of uncemented tibia components is to be expected in patients with poor bone quality. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Repair of bone segment defects with surface porous fiber-reinforced polymethyl methacrylate (PMMA) composite prosthesis: histomorphometric incorporation model and characterization by SEM.

PubMed

Hautamäki, Mikko P; Aho, Allan J; Alander, Pasi; Rekola, Jami; Gunn, Jarmo; Strandberg, Niko; Vallittu, Pekka K

2008-08-01

Polymer technology has provided solutions for filling of bone defects in situations where there may be technical or biological complications with autografts, allografts, and metal prostheses. We present an experimental study on segmental bone defect reconstruction using a polymethylmethacrylate-(PMMA-) based bulk polymer implant prosthesis. We concentrated on osteoconductivity and surface characteristics. A critical size segment defect of the rabbit tibia in 19 animals aged 18-24 weeks was reconstructed with a surface porous glass fiber-reinforced (SPF) prosthesis made of polymethylmethacrylate (PMMA). The biomechanical properties of SPF implant material were previously adjusted technically to mimic the properties of normal cortical bone. A plain PMMA implant with no porosity or fiber reinforcement was used as a control. Radiology, histomorphometry, and scanning electron microscopy (SEM) were used for analysis of bone growth into the prosthesis during incorporation. The radiographic and histological incorporation model showed good host bone contact, and strong formation of new bone as double cortex. Histomorphometric evaluation showed that the bone contact index (BCI) at the posterior surface interface was higher with the SPF implant than for the control. The total appositional bone growth over the posterior surface (area %) was also stronger for the SPF implant than for controls. Both bone growth into the porous surface and the BCI results were related to the quality, coverage, and regularity of the microstructure of the porous surface. Porous surface structure enhanced appositional bone growth onto the SPF implant. Under load-bearing conditions the implant appears to function like an osteoconductive prosthesis, which enables direct mobilization and rapid return to full weight bearing.

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

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

On the relationship between tibia torsional deformation and regional muscle contractions in habitual human exercises in vivo.

PubMed

Yang, Peng-Fei; Kriechbaumer, Andreas; Albracht, Kirsten; Sanno, Maximilian; Ganse, Bergita; Koy, Timmo; Shang, Peng; Brüggemann, Gert-Peter; Müller, Lars Peter; Rittweger, Jörn

2015-02-05

The mechanical relationship between bone and muscle has been long recognized. However, it still remains unclear how muscles exactly load on bone. In this study, utilizing an optical segment tracking technique, the in vivo tibia loading regimes in terms of tibia segment deformation in humans were investigated during walking, forefoot and rear foot stair ascent and running and isometric plantar flexion. Results suggested that the proximal tibia primarily bends to the posterior aspect and twists to the external aspect with respect to the distal tibia. During walking, peak posterior bending and peak torsion occurred in the first half (22%) and second half (76%) of the stance phase, respectively. During stair ascent, two noticeable peaks of torsion were found with forefoot strike (38% and 82% of stance phase), but only one peak of torsion was found with rear foot strike (78% of stance phase). The torsional deformation angle during both stair ascent and running was larger with forefoot strike than rear foot strike. During isometric plantar flexion, the tibia deformation regimes were characterized more by torsion (maximum 1.35°) than bending (maximum 0.52°). To conclude, bending and torsion predominated the tibia loading regimes during the investigated activities. Tibia torsional deformation is closely related to calf muscle contractions, which further confirm the notion of the muscle-bone mechanical link and shift the focus from loading magnitude to loading regimes in bone mechanobiology. It thus is speculated that torsion is another, yet under-rated factor, besides the compression and tension, to drive long bone mechano-adaptation. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

Intestinal pH and Absorption and Deposition of Ca 47 in the Rachitic Chick

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

Wasserman, R H; Taylor, A N

The effect of pH of the dosing solution on the relative tibia deposition of Ca 47 absorbed from the duodenum of rachitic and vit. D-treated chicks was examined. Vit. D had its usual enhancing effect on Ca 47 absorption; however, it was observed that the percent absorbed Ca47 deposited in tibia varied with intraduodenal pH and vit. D-status of the chick. At low pH values (1.9, 2.0), there were no differences in the percent of duodenally absorbed Ca 47 accumulated by tibia in rachitic or vit. D-treated chicks whereas, at high pH values, proportionally less of the absorbed Ca 47more » was deposited in rachitic tibia; pH was without effect on uptake of Ca 47 by tibia in the vit. D-treated birds.« less

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

The Contribution of Experimental in vivo Models to Understanding the Mechanisms of Adaptation to Mechanical Loading in Bone

PubMed Central

Meakin, Lee B.; Price, Joanna S.; Lanyon, Lance E.

2014-01-01

Changing loading regimens by natural means such as exercise, with or without interference such as osteotomy, has provided useful information on the structure:function relationship in bone tissue. However, the greatest precision in defining those aspects of the overall strain environment that influence modeling and remodeling behavior has been achieved by relating quantified changes in bone architecture to quantified changes in bones’ strain environment produced by direct, controlled artificial bone loading. Jiri Hert introduced the technique of artificial loading of bones in vivo with external devices in the 1960s using an electromechanical device to load rabbit tibiae through transfixing stainless steel pins. Quantifying natural bone strains during locomotion by attaching electrical resistance strain gages to bone surfaces was introduced by Lanyon, also in the 1960s. These studies in a variety of bones in a number of species demonstrated remarkable uniformity in the peak strains and maximum strain rates experienced. Experiments combining strain gage instrumentation with artificial loading in sheep, pigs, roosters, turkeys, rats, and mice has yielded significant insight into the control of strain-related adaptive (re)modeling. This diversity of approach has been largely superseded by non-invasive transcutaneous loading in rats and mice, which is now the model of choice for many studies. Together such studies have demonstrated that over the physiological strain range, bone’s mechanically adaptive processes are responsive to dynamic but not static strains; the size and nature of the adaptive response controlling bone mass is linearly related to the peak loads encountered; the strain-related response is preferentially sensitive to high strain rates and unresponsive to static ones; is most responsive to unusual strain distributions; is maximized by remarkably few strain cycles, and that these are most effective when interrupted by short periods of rest between them. PMID:25324829

Multi-Elemental Profiling of Tibial and Maxillary Trabecular Bone in Ovariectomised Rats

PubMed Central

Han, Pingping; Lu, Shifeier; Zhou, Yinghong; Moromizato, Karine; Du, Zhibin; Friis, Thor; Xiao, Yin

2016-01-01

Atomic minerals are the smallest components of bone and the content of Ca, being the most abundant mineral in bone, correlates strongly with the risk of osteoporosis. Postmenopausal women have a far greater risk of suffering from OP due to low Ca concentrations in their bones and this is associated with low bone mass and higher bone fracture rates. However, bone strength is determined not only by Ca level, but also a number of metallic and non-metallic elements in bone. Thus, in this study, the difference of metallic and non-metallic elements in ovariectomy-induced osteoporosis tibial and maxillary trabecular bone was investigated in comparison with sham operated normal bone by laser ablation inductively-coupled plasma mass spectrometry using a rat model. The results demonstrated that the average concentrations of 25Mg, 28Si, 39K, 47Ti, 56Fe, 59Co, 77Se, 88Sr, 137Ba, and 208Pb were generally higher in tibia than those in maxilla. Compared with the sham group, Ovariectomy induced more significant changes of these elements in tibia than maxilla, indicating tibial trabecular bones are more sensitive to changes of circulating estrogen. In addition, the concentrations of 28Si, 77Se, 208Pb, and Ca/P ratios were higher in tibia and maxilla in ovariectomised rats than those in normal bone at all time-points. The present study indicates that ovariectomy could significantly impact the element distribution and concentrations between tibia and maxilla. PMID:27338361

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

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.

[Intramedullary nailing of the distal tibia illustrated with the Expert(TM) tibia nail].

PubMed

El Attal, R; Hansen, M; Rosenberger, R; Smekal, V; Rommens, P M; Blauth, M

2011-12-01

Restoration of axis, length, and rotation of the lower leg. Sufficient primary stability of the osteosynthesis for functional aftercare and to maintain joint mobility. Good bony healing in closed and open fractures. Closed and open fractures of the tibia and complete lower leg fractures distal to the isthmus (AO 42), extraarticular fractures of the distal tibia (AO 43 A1/A2/A3), segmental fractures of the tibia with a fracture in the distal tibia, and certain intraarticular fractures of the distal tibia without impression of the joint line with the use of additional implants (AO 43 C1) Patient in reduced general condition (e.g., bed ridden), flexion of the knee of less than 90°, patients with knee arthroplasty of the affected leg, infection in the area of the nail's insertion, infection of the tibial cavity, complex articular fractures of the proximal or distal tibia with joint depression. Closed reduction of the fracture preferably on a fracture table or using a distractor or an external fixation frame. If necessary, use pointed reduction clamps or sterile drapery. In some cases, additional implants like percutaneous small fragment screws, poller screws or k-wires are helpful. Open reduction is rarely necessary and must be avoided. Opening of the proximal tibia in line with the medullary canal. Canulated insertion of the Expert(TM) tibia nail (ETN; Synthes GmbH, Oberdorf, Switzerland) with reaming of the medullary canal. Control of axis, length, and rotation. Distal interlocking with the radiolucent drill and proximal interlocking with the targeting device. Immediate mobilization of ankle and knee joint. Mobilization with 20 kg weight-bearing with crutches. X-ray control 6 weeks postoperatively and increased weight-bearing depending on the fracture status. In cases with simple fractures, good bony contact, or transverse fracture pattern, full weight-bearing at the end of week 6 is targeted. Between July 2004 and May 2005, 180 patients were included in a multicenter study. The follow-up rate was 81% after 1 year. Of these, 91 fractures (50.6%) were located in the distal third of the tibia. In this segment, the rate of delayed union was 10.6%. Malalignment of > 5° was observed in 5.4%. A secondary malalignment after initial good reduction was detected in only 1.1% of all cases. The implant-specific risk for screw breakage was 3.2%. One patient sustained a deep infection. If additional fibula plating was performed an 8-fold higher risk for delayed bone healing was observed (95%CI: 2.9-21.2, p< 0.001). If the fracture of the fibula was at the same height as on the tibia, the risk for delayed healing was even 14-fold (95% CI: 3.4-62.5, p< 0.001). Biomechanically plating of the fibula does not increase stability in suprasyndesmal distal tibia-fibular fractures treated with an intramedullary nail. Using the ETN with its optimized locking options, fibula plating is not recommended, thus, avoiding soft tissue problems and potentially delayed bone healing.

Computational analysis of the human sinus node action potential: model development and effects of mutations

PubMed Central

Fabbri, Alan; Fantini, Matteo; Wilders, Ronald

2017-01-01

Key points We constructed a comprehensive mathematical model of the spontaneous electrical activity of a human sinoatrial node (SAN) pacemaker cell, starting from the recent Severi–DiFrancesco model of rabbit SAN cells.Our model is based on electrophysiological data from isolated human SAN pacemaker cells and closely matches the action potentials and calcium transient that were recorded experimentally.Simulated ion channelopathies explain the clinically observed changes in heart rate in corresponding mutation carriers, providing an independent qualitative validation of the model.The model shows that the modulatory role of the ‘funny current’ (I f) in the pacing rate of human SAN pacemaker cells is highly similar to that of rabbit SAN cells, despite its considerably lower amplitude.The model may prove useful in the design of experiments and the development of heart‐rate modulating drugs. Abstract The sinoatrial node (SAN) is the normal pacemaker of the mammalian heart.  Over several decades, a large amount of data on the ionic mechanisms underlying the spontaneous electrical activity of SAN pacemaker cells has been obtained, mostly in experiments on single cells isolated from rabbit SAN. This wealth of data has allowed the development of mathematical models of the electrical activity of rabbit SAN pacemaker cells. The present study aimed to construct a comprehensive model of the electrical activity of a human SAN pacemaker cell using recently obtained electrophysiological data from human SAN pacemaker cells.  We based our model on the recent Severi–DiFrancesco model of a rabbit SAN pacemaker cell. The action potential and calcium transient of the resulting model are close to the experimentally recorded values. The model has a much smaller ‘funny current’ (I f) than do rabbit cells, although its modulatory role is highly similar. Changes in pacing rate upon the implementation of mutations associated with sinus node dysfunction agree with the clinical observations. This agreement holds for both loss‐of‐function and gain‐of‐function mutations in the HCN4, SCN5A and KCNQ1 genes, underlying ion channelopathies in I f, fast sodium current and slow delayed rectifier potassium current, respectively. We conclude that our human SAN cell model can be a useful tool in the design of experiments and the development of drugs that aim to modulate heart rate. PMID:28185290

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.

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)

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.

Ability of modern distal tibia plates to stabilize comminuted pilon fracture fragments: Is dual plate fixation necessary?

PubMed

Penny, Phillip; Swords, Michael; Heisler, Jason; Cien, Adam; Sands, Andrew; Cole, Peter

2016-08-01

The purpose of this study was to examine the screw trajectory of ten commercially available distal tibia plates and compare them to common fracture patterns seen in OTA C type pilon fractures to determine their ability to stabilize the three most common fracture fragments while buttressing anterolateral zones of comminution. We hypothesized that a single plate for the distal tibia would fail to adequately stabilize all three main fracture fragments and zones of comminution in complex pilon fractures. Ten synthetic distal tibia sawbones models were used in conjunction with ten different locking distal tibia plate designs from three manufacturers (Depuy Synthes, J&J Co, Paoli, PA; Smith & Nephew, Memphis, TN; and Stryker, Mawa, NJ). Both medial and anterolateral plates from each company were utilized and separately applied to an individual sawbone model. Three implants allowing variable angle screw placement were used. The location of the locking screws and buttress effect 1cm above the articular surface was noted for each implant using axial computed tomography (CT). The images were then compared to a recently published "pilon fracture map" using an overlay technique to establish the relationship between screw location and known common fracture lines and areas of comminution. Each of the three main fragments was considered "captured" by a screw if it was purchased by at least two screws thereby controlling rotational forces on each fragment. Three of four anterolateral plates lacked stable fixation in the medial fragment. Of the 4 anterolateral plates used, only the variable angle anterolateral plate by Depuy Synthes captured the medial fragment with two screws. All four anterolateral plates buttressed the area of highest comminution and had an average of 1.25 screws in the medial fragment and an average of 3 screws in the posterolateral fragment. All five direct medial plates had variable fixation within anterolateral and posterolateral fragments with an average of 1.8 screws in the anterolateral fragment and an average of 1.3 screws in the posterolateral fragment. The Depuy Synthes variable angle anterolateral plate allowed for fixation of the medial fragment with two screws while simultaneously buttressing the zone of highest comminution and capturing both the anterolateral and posterolateral fragments with five and three screws respectively. The variable angle anteromedial plate by Depuy Synthes captured all three main fracture fragments but it did not buttress the anterolateral zone of comminution. In OTA 43C type pilon fractures, 8 out of 10 studied commercially available implants precontoured for the distal tibia, do not adequately stabilize the three primary fracture fragments typically seen in these injuries. Anterolateral plates were superior in addressing the coronal primary fracture line across the apex of the plafond, and buttressing the zone of comminution. None of the available plates can substitute for an understanding of the fracture planes and fragments typically seen in complex intra-articular tibia fractures and the addition of a second plate is necessary for adequate stability. Level IV. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

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.

Effect of the starting point of half-pin insertion on the insertional torque of the pin at the tibia.

PubMed

Kim, Sung Jae; Kim, Sung Hwan; Kim, Young Hwan; Chun, Yong Min

2015-01-01

The authors have observed a failure to achieve secure fixation in elderly patients when inserting a half-pin at the anteromedial surface of the tibia. The purpose of this study was to compare two methods for inserting a half-pin at tibia diaphysis in elderly patients. Twenty cadaveric tibias were divided into Group C or V. A half-pin was inserted into the tibias of Group C via the conventional method, from the anteromedial surface to the interosseous border of the tibia diaphysis, and into the tibias of Group V via the vertical method, from the anterior border to the posterior surface at the same level. The maximum insertion torque was measured during the bicortical insertion with a torque driver. The thickness of the cortex was measured by micro-computed tomography. The relationship between the thickness of the cortex engaged and the insertion torque was investigated. The maximum insertion torque and the thickness of the cortex were significantly higher in Group V than Group C. Both groups exhibited a statistically significant linear correlation between torque and thickness by Spearman's rank correlation analysis. Half-pins inserted by the vertical method achieved purchase of more cortex than those inserted by the conventional method. Considering that cortical thickness and insertion torque in Group V were significantly greater than those in Group C, we suggest that the vertical method of half-pin insertion may be an alternative to the conventional method in elderly patients.

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

Growth of C57BL/6 mice and the material and mechanical properties of cortical bone from the tibia.

PubMed

Somerville, J M; Aspden, R M; Armour, K E; Armour, K J; Reid, D M

2004-05-01

Murine models are becoming increasingly important for studying skeletal growth and regulation because of the relative ease with which their genomes can be manipulated. This study measured the changes in cortical bone of tibiae from one of the more common models, the C57Bl/6, as a function of aging. A total of 97 mice, male and female, were studied at the ages of 1, 2, 3, 6, 9, and 12 months. The body weight of the animals, the length of the tibiae, the composition (in terms of mineral and organic mass fractions), and the density and modulus of the bone were measured. Peripheral quantitative computed tomography was also used to measure bone mineral density (BMD), total and cortical areas, and the cross-sectional moment of inertia. Most parameters measured followed a growth-like curve, which leveled off some time before 6 months of age. Bone composition and modulus were the same at maturity in both sexes, but there were sex-related differences in the modulus with aging. Dimensional measurements and the density of the bone showed significant differences between male and female animals at all ages, with the male mice having larger values. Skeletal maturity for most factors in C57Bl/6 mice has been reached before the age of 6 months.

The effect of both a thoracic trauma and a soft-tissue trauma on fracture healing in a rat model

PubMed Central

2011-01-01

Background and purpose There is some clinical evidence that fracture healing is impaired in multiply injured patients. Nothing is known, however, about the effects of various types of injuries and their contribution to a possible disturbance of the fracture-healing process. We investigated the effect of a thoracic trauma and an additional soft-tissue trauma on fracture healing in a rat tibia model. Methods 3 groups of rats were operated: group A with a simple fracture of the tibia and fibula, group B with a fracture and an additional thoracic trauma, and group C with a fracture, thoracic trauma, and an additional soft-tissue trauma. The fracture and the soft-tissue injury were produced by a special guillotine-like device and the thoracic trauma by a blast wave generator. After one day, the serum level of IL-6 was quantified, and at the end of the study (28 days) the mechanical properties and the callus volume of the healed tibia were determined. Results Increasing the severity of the injury caused IL-6 levels to more than double 1 day after injury. It halved the load to failure in mechanical tests and led to reduced callus volume after 28 days of healing. Interpretation Fracture healing is impaired when additional thoracic trauma and soft tissue trauma occurs. PMID:21463222

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.

Longitudinal changes in bone lead levels: the VA Normative Aging Study

PubMed Central

Wilker, Elissa; Korrick, Susan; Nie, Linda H; Sparrow, David; Vokonas, Pantel; Coull, Brent; Wright, Robert O.; Schwartz, Joel; Hu, Howard

2011-01-01

Objective Bone lead is a cumulative measure of lead exposure that can also be remobilized. We examined repeated measures of bone lead over 11 years to characterize long-term changes and identify predictors of tibia and patella lead stores in an elderly male population. Methods Lead was measured every 3–5 years by k-x-ray fluorescence and mixed-effect models with random effects were used to evaluate change over time. Results 554 participants provided up to 4 bone lead measurements. Final models predicted a −1.4% annual decline (95%CI: −2.2,−0.7) for tibia lead and piecewise linear model for patella with an initial decline of 5.1% per year (95%CI: −6.2,−3.9) during the first 4.6 years but no significant change thereafter (−0.4% (95% CI: −2.4, 1.7)). Conclusions These results suggest that bone lead half-life may be longer than previously reported. PMID:21788910

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.

Anterior iliac crest, posterior iliac crest, and proximal tibia donor sites: a comparison of cancellous bone volumes in fresh cadavers.

PubMed

Engelstad, Mark E; Morse, Timothy

2010-12-01

The anterior iliac crest, posterior iliac crest, and proximal tibia are common cancellous donor sites used for autogenous bone grafting. Donor site selection is partly dependent on the expected volume of available bone, but reports of cancellous bone volumes at each of these sites are variable. The goal of this study was to compare the volumes of cancellous bone harvested from donor sites within the same cadaver. Within each of 10 fresh frozen cadavers, cancellous bone was harvested from 3 donor sites-anterior iliac crest, posterior iliac crest, and proximal tibia-using established surgical techniques. Bone volumes were measured by fluid displacement. Mean compressed cancellous bone volumes from the 3 donor sites were compared among cadavers. Within each cadaver, the 3 donor sites were given a volume rank score from 1 (least volume) to 3 (most volume). Among cadavers, mean compressed cancellous bone volumes from the proximal tibia (11.3 mL) and posterior iliac crest (10.1 mL) were significantly greater than the anterior iliac crest (7.0 mL). Within cadavers, the mean volume rank score of the proximal tibia (mean rank, 2.7) was statistically greater than that for the posterior iliac crest (mean rank, 2.0), which was statistically greater than that for the anterior iliac crest (mean rank, 1.2). Strong correlations in bone volume existed between the proximal tibia and iliac crests (r = 0.67) and between the anterior iliac crest and posterior iliac crest (r = 0.93). The proximal tibia and posterior iliac crest yielded a significantly greater mean volume of compressed cancellous bone than the anterior iliac crest. Within individual cadaver skeletons, the proximal tibia was most likely to yield the largest cancellous volume, whereas the anterior iliac crest was most likely to yield the smallest cancellous volume. Although the proximal tibia contains relatively large volumes of cancellous bone, further investigation is required to determine how much cancellous bone can safely be harvested. Copyright © 2010 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

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.

Appendicular and whole body lean mass outcomes are associated with finite element analysis-derived bone strength at the distal radius and tibia in adults aged 40years and older.

PubMed

Gibbs, Jenna C; Giangregorio, Lora M; Wong, Andy K O; Josse, Robert G; Cheung, Angela M

2017-10-01

The purpose of this cross-sectional study was to determine how appendicular lean mass index (ALMI), and whole body lean (LMI) and fat mass indices (FMI) associate with estimated bone strength outcomes at the distal radius and tibia in adults aged 40 years and older. Dual energy X-ray absorptiometry (DXA) scans were performed to determine body composition, including whole body lean and fat mass, and appendicular lean mass. ALMI (appendicular lean mass/height 2 ), LMI (lean tissue mass/height 2 ) and FMI (fat mass/height 2 ) were calculated. High-resolution peripheral quantitative computed tomography (HRpQCT) scans were performed to assess bone structural properties at the distal radius and tibia. Using finite element analysis, failure load (N), stiffness (N/mm), ultimate stress (MPa), and cortical-to-trabecular load ratio were estimated from HRpQCT scans. The associations between body composition (ALMI, LMI, FMI) and estimated bone strength were examined using bivariate and multivariable linear regression analyses adjusting for age, sex, and other confounding variables. In 197 participants (127 women; mean±SD, age: 69.5±10.3y, body mass index: 27.95±4.95kg/m 2 , ALMI: 7.31±1.31kg/m 2 ), ALMI and LMI were significantly associated with failure load at the distal radius and tibia (explained 39%-48% of the variance) and remained significant after adjusting for confounding variables and multiple testing (R 2 =0.586-0.645, p<0.001). ALMI, LMI, and FMI did not have significant associations with ultimate stress in our multivariable models. FMI was significantly associated with cortical-to-trabecular load ratio at the distal radius and tibia (explained 6%-12% of the variance) and remained significant after adjusting for confounders and multiple testing (R 2 =0.208-0.243, p<0.001). FMI was no longer significantly associated with failure load after adjusting for confounders. These findings suggest that ALMI and LMI are important determinants of estimated bone strength, particularly failure load, at the distal radius and tibia, and may contribute to preservation of bone strength in middle-to-late adulthood. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of multi-deficiencies-diet on bone parameters of peripheral bone in ovariectomized mature rat.

PubMed

El Khassawna, Thaqif; Böcker, Wolfgang; Govindarajan, Parameswari; Schliefke, Nathalie; Hürter, Britta; Kampschulte, Marian; Schlewitz, Gudrun; Alt, Volker; Lips, Katrin Susanne; Faulenbach, Miriam; Möllmann, Henriette; Zahner, Daniel; Dürselen, Lutz; Ignatius, Anita; Bauer, Natali; Wenisch, Sabine; Langheinrich, Alexander Claus; Schnettler, Reinhard; Heiss, Christian

2013-01-01

Many postmenopausal women have vitamin D and calcium deficiency. Therefore, vitamin D and calcium supplementation is recommended for all patients with osteopenia and osteoporosis. We used an experimental rat model to test the hypothesis that induction of osteoporosis is more efficiently achieved in peripheral bone through combining ovariectomy with a unique multi-deficiencies diet (vitamin D depletion and deficient calcium, vitamin K and phosphorus). 14-week-old Sprague-Dawley rats served as controls to examine the initial bone status. 11 rats were bilaterally ovariectomized (OVX) and fed with multi-deficiencies diet. Three months later the treated group and the Sham group (n = 8) were euthanized. Bone biomechanical competence of the diaphyseal bone was examined on both, tibia and femur. Image analysis was performed on tibia via µCT, and on femur via histological analysis. Lower torsional stiffness indicated inferior mechanical competence of the tibia in 3 month OVX+Diet. Proximal metaphyseal region of the tibia showed a diminished bone tissue portion to total tissue in the µCT despite the increased total area as evaluated in both µCT and histology. Cortical bone showed higher porosity and smaller cross sectional thickness of the tibial diaphysis in the OVX+Diet rats. A lower ALP positive area and elevated serum level of RANKL exhibited the unbalanced cellular interaction in bone remodeling in the OVX+Diet rat after 3 month of treatment. Interestingly, more adipose tissue area in bone marrow indicated an effect of bone loss similar to that observed in osteoporotic patients. Nonetheless, the presence of osteoid and elevated serum level of PTH, BGP and Opn suggest the development of osteomalacia rather than an osteoporosis. As the treatment and fracture management of both osteoporotic and osteomalacia patients are clinically overlapping, this study provides a preclinical animal model to be utilized in local supplementation of minerals, drugs and growth factors in future fracture healing studies.

Effects of Multi-Deficiencies-Diet on Bone Parameters of Peripheral Bone in Ovariectomized Mature Rat

PubMed Central

El Khassawna, Thaqif; Böcker, Wolfgang; Govindarajan, Parameswari; Schliefke, Nathalie; Hürter, Britta; Kampschulte, Marian; Schlewitz, Gudrun; Alt, Volker; Lips, Katrin Susanne; Faulenbach, Miriam; Möllmann, Henriette; Zahner, Daniel; Dürselen, Lutz; Ignatius, Anita; Bauer, Natali; Wenisch, Sabine; Langheinrich, Alexander Claus; Schnettler, Reinhard; Heiss, Christian

2013-01-01

Many postmenopausal women have vitamin D and calcium deficiency. Therefore, vitamin D and calcium supplementation is recommended for all patients with osteopenia and osteoporosis. We used an experimental rat model to test the hypothesis that induction of osteoporosis is more efficiently achieved in peripheral bone through combining ovariectomy with a unique multi-deficiencies diet (vitamin D depletion and deficient calcium, vitamin K and phosphorus). 14-week-old Sprague-Dawley rats served as controls to examine the initial bone status. 11 rats were bilaterally ovariectomized (OVX) and fed with multi-deficiencies diet. Three months later the treated group and the Sham group (n = 8) were euthanized. Bone biomechanical competence of the diaphyseal bone was examined on both, tibia and femur. Image analysis was performed on tibia via µCT, and on femur via histological analysis. Lower torsional stiffness indicated inferior mechanical competence of the tibia in 3 month OVX+Diet. Proximal metaphyseal region of the tibia showed a diminished bone tissue portion to total tissue in the µCT despite the increased total area as evaluated in both µCT and histology. Cortical bone showed higher porosity and smaller cross sectional thickness of the tibial diaphysis in the OVX+Diet rats. A lower ALP positive area and elevated serum level of RANKL exhibited the unbalanced cellular interaction in bone remodeling in the OVX+Diet rat after 3 month of treatment. Interestingly, more adipose tissue area in bone marrow indicated an effect of bone loss similar to that observed in osteoporotic patients. Nonetheless, the presence of osteoid and elevated serum level of PTH, BGP and Opn suggest the development of osteomalacia rather than an osteoporosis. As the treatment and fracture management of both osteoporotic and osteomalacia patients are clinically overlapping, this study provides a preclinical animal model to be utilized in local supplementation of minerals, drugs and growth factors in future fracture healing studies. PMID:23977109

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

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.

Identification tibia and fibula bone fracture location using scanline algorithm

NASA Astrophysics Data System (ADS)

Muchtar, M. A.; Simanjuntak, S. E.; Rahmat, R. F.; Mawengkang, H.; Zarlis, M.; Sitompul, O. S.; Winanto, I. D.; Andayani, U.; Syahputra, M. F.; Siregar, I.; Nasution, T. H.

2018-03-01

Fracture is a condition that there is a damage in the continuity of the bone, usually caused by stress, trauma or weak bones. The tibia and fibula are two separated-long bones in the lower leg, closely linked at the knee and ankle. Tibia/fibula fracture often happen when there is too much force applied to the bone that it can withstand. One of the way to identify the location of tibia/fibula fracture is to read X-ray image manually. Visual examination requires more time and allows for errors in identification due to the noise in image. In addition, reading X-ray needs highlighting background to make the objects in X-ray image appear more clearly. Therefore, a method is required to help radiologist to identify the location of tibia/fibula fracture. We propose some image-processing techniques for processing cruris image and Scan line algorithm for the identification of fracture location. The result shows that our proposed method is able to identify it and reach up to 87.5% of accuracy.

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.

Asymmetric bone adaptations to soleus mechanical loading after spinal cord injury

PubMed Central

Dudley-Javoroski, S.; Shields, R.K.

2009-01-01

The purpose of this report is to examine longitudinal bone mineral density (BMD) changes in individuals with spinal cord injury (SCI) who began unilateral soleus electrical stimulation early after injury. Twelve men with SCI and seven without SCI underwent peripheral quantitative computed tomography assessment of distal tibia BMD. After 4.5 to 6 years of training, average trained limb BMD was 27.5% higher than untrained limb BMD. The training effect was more pronounced in the central core of the tibia cross-section (40.5% between-limb difference). No between-limb difference emerged in the anterior half of the tibia (19.2 mg/cm3 difference, p>0.05). A robust between-limb difference emerged in the posterior half of the tibia (76.1 mg/cm3 difference, p=0.0439). The posterior tibia BMD of one subject remained within the range of non-SCI values for 3.8 years post-SCI. The results support that the constrained orientation of soleus mechanical loads, administered over several years, elicited bone-sparing effects in the posterior tibia. This study provides a demonstration of the bone-protective potential of a carefully controlled dose of mechanical load. The specific orientation of applied mechanical loads may strongly influence the manifestation of BMD adaptations in humans with SCI. PMID:18799855

Effects of feeding different concentration and forms of zinc on the performance and tissue mineral status of broiler chicks.

PubMed

Ao, T; Pierce, J L; Pescatore, A J; Cantor, A H; Dawson, K A; Ford, M J; Paul, M

2011-08-01

1. Two studies were conducted to investigate the effect of feeding different concentration and forms of zinc (Zn) on the performance and tibia Zn status of broiler chicks. 2. In Experiment 1, chicks fed on the control or the diet supplemented with 12?mg of Zn as sulphate had lower feed intake, weight gain and tibia Zn content than other treatment groups. Chicks given 12 and 24 mg of organic Zn in starter and grower phases, respectively, had the same performance and tibia Zn content as those fed 40 mg of Zn as sulphate and the same performance but higher tibia Zn content than those given 12 mg of Zn as organic over the 42 d. 3. In Experiment 2, chicks given 24 mg organic Zn had greater weight gain than chicks fed on the other treatment diets in the starter period. Chicks fed on the control diet had lower tibia Zn content than chicks fed other treatment diets. Chicks given 80 mg Zn as sulphate had higher tibia Zn content than chicks fed the other treatment diets except those given 40 mg of Zn as sulphate. 4. The results from these trials indicate that feeding lower concentration of Zn as organic form may better promote the growth performance of broiler chicks.

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

The effect of retained intramedullary nails on tibial bone mineral density.

PubMed

Allen, J C; Lindsey, R W; Hipp, J A; Gugala, Z; Rianon, N; LeBlanc, A

2008-07-01

Intramedullary nailing has become a standard treatment for adult tibial shaft fractures. Retained intramedullary nails have been associated with stress shielding, although their long-term effect on decreasing tibial bone mineral density is currently unclear. The purpose of this study was to determine if retained tibial intramedullary nails decrease tibial mineral density in patients with successfully treated fractures. Patients treated with statically locked intramedullary nails for isolated, unilateral tibia shaft fractures were studied. Inclusion required that fracture had healed radiographically and that the patient returned to the pre-injury activity level. Data on patient demographic, fracture type, surgical technique, implant, and post-operative functional status were tabulated. Dual energy X-ray absorptiometry was used to measure bone mineral density in selected regions of the affected tibia and the contralateral intact tibia. Image reconstruction software was employed to ensure symmetry of the studied regions. Twenty patients (mean age 43; range 22-77 years) were studied at a mean of 29 months (range 5-60 months) following intramedullary nailing. There was statistically significant reduction of mean bone mineral density in tibiae with retained intramedullary nails (1.02 g/cm(2) versus 1.06 g/cm(2); P=0.04). A significantly greater decrease in bone mineral density was detected in the reamed versus non-reamed tibiae (-7% versus +6%, respectively; P<0.05). The present study demonstrates a small, but statistically significant overall bone mineral density decrease in healed tibiae with retained nails. Intramedullary reaming appears to be a factor potentiating the reduction of tibia bone mineral density in long-term nail retention.

Longitudinal shapes of the tibia and femur are unrelated and variable.

PubMed

Howell, Stephen M; Kuznik, Kyle; Hull, Maury L; Siston, Robert A

2010-04-01

In general practice, short films of the knee are used to assess component position and define the entry point for intramedullary femoral alignment in TKAs; however, whether it is justified to use the short film commonly used in research settings and everyday practice as a substitute for the whole leg view is controversial and needs clarification. In 138 long leg CT scanograms we measured the angle formed by the anatomic axis of the proximal fourth of the tibia and the mechanical axis of the tibia, the angle formed by the anatomic axis of the distal fourth of the femur and the mechanical axis of the femur, the "bow" of the tibia (as reflected by the offset of the anatomic axis from the center of the talus), and the "bow" of the femur (as reflected by the offset of the anatomic axis from the center of the femoral head). Because the angle formed by these axes and the bow of the tibia and femur have wide variability in females and males, a short film of the knee should not be used in place of the whole leg view when accurate assessment of component position and limb alignment is essential. A previous study of normal limbs found that only 2% of subjects have a neutral hip-knee-ankle axis, which can be explained by the wide variability of the bow in the tibia and femur and the lack of correlation between the bow of the tibia and femur in a given limb as shown in the current study.

Effect of a novel microbial phytase on production performance and tibia mineral concentration in broiler chickens given low-calcium diets.

PubMed

Singh, A; Walk, C L; Ghosh, T K; Bedford, M R; Haldar, S

2013-01-01

1. In a 42-d feeding trial, 264 one-d-old, as hatched, Cobb 400 broiler chickens (6 pens per group, n = 11 per pen in a 2 × 2 factorial arrangement) were fed on two concentrations of dietary calcium (Ca) (9.0 and 7.5 g/kg in starter, 7.5 and 6 g/kg in grower phases) and supplemental phytase (0 and 500 U/kg diet). 2. During d 0-21, the high Ca + phytase diet improved body weight. During d 0-42, feed intake was increased by the low Ca diet and decreased by phytase supplementation. Feed conversion ratio during d 0-21 was improved by the high Ca + phytase diet. 3. At d 42, Ca in duodenal digesta was reduced by low dietary Ca and supplemental phytase. High dietary Ca reduced P in duodenal and jejunal digesta. Phytase reduced digesta P and increased serum P concentration. 4. Relative tibia length decreased with low dietary Ca and increased with phytase. The robusticity index of tibia was improved by the low Ca diet and phytase supplementation. Phytase supplementation increased tibia ash and concentrations of Ca, magnesium (Mg), manganese (Mn), copper (Cu), zinc (Zn) and iron (Fe) in tibia. The low Ca diet increased Mg, Mn and Fe and reduced Cu and Zn in tibia. 5. It was concluded that 7.5 g Ca/kg during weeks 0-3 and 6 g Ca/kg during weeks 3-6 sustained broiler performance and bone ash, while phytase supplementation facilitated tibia mineralisation, particularly during the grower phase.

Analysis of crash parameters and driver characteristics associated with lower limb injury.

PubMed

Ye, Xin; Poplin, Gerald; Bose, Dipan; Forbes, Aaron; Hurwitz, Shepard; Shaw, Greg; Crandall, Jeff

2015-10-01

This study aims to investigate changes in frequency, risk, and patterns of lower limb injuries due to vehicle and occupant parameters as a function of vehicle model year. From the National Automotive Sampling System-Crashworthiness Data System, 10,988 observations were sampled and analyzed, representing 4.7 million belted drivers involved in frontal crashes for the years 1998-2010. A logistic regression model was developed to understand the association of sustaining knee and below knee lower limb injuries of moderate or greater severity with motor vehicle crash characteristics such as vehicle type and model years, toepan and instrument panel intrusions in addition to the occupant's age, gender, height and weight. Toepan intrusion greater than 2cm was significantly associated with an increased likelihood of injury (odds ratio: 9.10, 95% confidence interval 1.82-45.42). Females sustained a higher likelihood of distal lower limb injuries (OR: 6.83, 1.56-29.93) as compared to males. Increased mass of the driver was also found to have a positive association with injury (OR: 1.04, 1.02-1.06), while age and height were not associated with injury likelihood. Relative to passenger cars, vans exhibited a protective effect against sustaining lower limb injury (OR: 0.24, 0.07-0.78), whereas no association was shown for light trucks (OR: 1.31, 0.69-2.49) or SUVs (OR: 0.76, 0.28-2.02). To examine whether current crash testing results are representative of real-world NASS-CDS findings, data from frontal offset crash tests performed by the Insurance Institute for Highway Safety (IIHS) were examined. IIHS data indicated a decreasing trend in vehicle foot well and toepan intrusion, foot accelerations, tibia axial forces and tibia index in relation to increasing vehicle model year between the year 1995 and 2013. Over 90% of vehicles received the highest IIHS rating, with steady improvement from the upper and lower tibia index, tibia axial force and the resultant foot acceleration considering both left and right extremities. Passenger cars received the highest rating followed by SUVs and light trucks, while vans attained the lowest rating. These results demonstrate that while there has been steady improvement in vehicle crash test performance, below-knee lower extremity injuries remain the most common AIS 2+ injury in real-world frontal crashes. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

Wrapping grafting for congenital pseudarthrosis of the tibia

PubMed Central

Yan, An; Mei, Hai-Bo; Liu, Kun; Wu, Jiang-Yan; Tang, Jin; Zhu, Guang-Hui; Ye, Wei-Hua

2017-01-01

Abstract Objective: Treatment of congenital pseudarthrosis of the tibia (CPT) remains a challenge. The autogenic iliac bone graft is important consistent of treatment for CPT. The purpose of this study was to investigate the role of wrapping autogenic iliac bone graft in improvement of the curing opportunities of CPT. Methods: We combined Ilizarov fixator with intramedullary rodding of the tibia and wrapping autogenic iliac bone graft for treatment 51 cases of CPT between 2007 and 2010. The mean age is 3.2 years at index operation, of which 31 patients (61%) were below 3 years old. According to Crawford classification, 5 tibia had type-II morphology; 3, type-III; 43, type-IV. Results: In the postoperative follow-up of 3.5 months (range from 3 to 4.5 months), all cases were found that the bone graft sites of pseudarthrosis of the tibia showed a significant augmentation and spindle-shaped expansion as obvious change. All cases of this series have been followed-up, average followed-up time were 1.6 years (range from 7 to 3.1 years), of which 19 cases were more than 2 years. The average time of removed the Ilizarov ring fixator was 3.5 months (range from 3 to 4.5 months). According to Johnston Clinical evaluation system, 26 cases had grade I, 21 cases, grade II, 4 cases, grade III. Following the Ohnishi X-ray evaluation criteria, union of pseudarthrosis of the tibia were 42 cases, delayed union 5 cases, nonunion 4 cases. Conclusion: Autogenic iliac bone graft is able to offer the activity of osteoblasts and osteogenesis induced by bone morphogenetic protein (BMP) and glycoprotein, meanwhile enclosing bone graft could help keep cancellous bone fragments in close contact around pseudarthrosis of the tibia, allowing the formation of high concentration of glycoprotein and BMP induced by chemical factors because of established the sealing environment in location, all of which could enhance the healing of pseudarthrosis of the tibia. PMID:29310362

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.

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

Ricafort, Juliet

A model was developed to determine the forces exerted by several flexor and extensor muscles of the human knee under static conditions. The following muscles were studied: the gastrocnemius, biceps femoris, semitendinosus, semimembranosus, and the set of quadricep muscles. The tibia and fibula were each modeled as rigid bodies; muscles were modeled by their functional lines of action in space. Assumptions based on previous data were used to resolve the indeterminacy.

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.

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.

Principal Component Analysis in Construction of 3D Human Knee Joint Models Using a Statistical Shape Model Method

PubMed Central

Tsai, Tsung-Yuan; Li, Jing-Sheng; Wang, Shaobai; Li, Pingyue; Kwon, Young-Min; Li, Guoan

2013-01-01

The statistical shape model (SSM) method that uses 2D images of the knee joint to predict the 3D joint surface model has been reported in literature. In this study, we constructed a SSM database using 152 human CT knee joint models, including the femur, tibia and patella and analyzed the characteristics of each principal component of the SSM. The surface models of two in vivo knees were predicted using the SSM and their 2D bi-plane fluoroscopic images. The predicted models were compared to their CT joint models. The differences between the predicted 3D knee joint surfaces and the CT image-based surfaces were 0.30 ± 0.81 mm, 0.34 ± 0.79 mm and 0.36 ± 0.59 mm for the femur, tibia and patella, respectively (average ± standard deviation). The computational time for each bone of the knee joint was within 30 seconds using a personal computer. The analysis of this study indicated that the SSM method could be a useful tool to construct 3D surface models of the knee with sub-millimeter accuracy in real time. Thus it may have a broad application in computer assisted knee surgeries that require 3D surface models of the knee. PMID:24156375

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.

Bone shape difference between control and osteochondral defect groups of the ankle joint.

PubMed

Tümer, N; Blankevoort, L; van de Giessen, M; Terra, M P; de Jong, P A; Weinans, H; Tuijthof, G J M; Zadpoor, A A

2016-12-01

The etiology of osteochondral defects (OCDs), for which the ankle (talocrural) joint is one of the common sites, is not yet fully understood. In this study, we hypothesized that bone shape plays a role in development of OCDs. Therefore, we quantitatively compared the morphology of the talus and the distal tibia between an OCD group and a control group. The shape variations of the talus and distal tibia were described separately by constructing two statistical shape models (SSMs) based on the segmentation of the bones from ankle computed tomography (CT) scans obtained from control (i.e., 35 CT scans) and OCD (i.e., 37 CT scans) groups. The first five modes of shape variation for the SSM corresponding to each bone were statistically compared between control and OCD groups using an analysis of variance (ANOVA) corrected with the Bonferroni for multiple comparisons. The first five modes of variation in the SSMs respectively represented 49% and 40% of the total variance of talus and tibia. Less than 5% of the variance per mode was described by the higher modes. Mode 5 of the talus (P = 0.004) primarily describing changes in the vertical neck angle and Mode 1 of the tibia (P < 0.0001) representing variations at the medial malleolus, showed statistically significant difference between the control and OCD groups. Shape differences exist between control and OCD groups. This indicates that a geometry modulated biomechanical behavior of the talocrural joint may be a risk factor for OCD. Copyright © 2016. Published by Elsevier Ltd.

Disregarding population specificity: its influence on the sex assessment methods from the tibia.

PubMed

Kotěrová, Anežka; Velemínská, Jana; Dupej, Ján; Brzobohatá, Hana; Pilný, Aleš; Brůžek, Jaroslav

2017-01-01

Forensic anthropology has developed classification techniques for sex estimation of unknown skeletal remains, for example population-specific discriminant function analyses. These methods were designed for populations that lived mostly in the late nineteenth and twentieth centuries. Their level of reliability or misclassification is important for practical use in today's forensic practice; it is, however, unknown. We addressed the question of what the likelihood of errors would be if population specificity of discriminant functions of the tibia were disregarded. Moreover, five classification functions in a Czech sample were proposed (accuracies 82.1-87.5 %, sex bias ranged from -1.3 to -5.4 %). We measured ten variables traditionally used for sex assessment of the tibia on a sample of 30 male and 26 female models from recent Czech population. To estimate the classification accuracy and error (misclassification) rates ignoring population specificity, we selected published classification functions of tibia for the Portuguese, south European, and the North American populations. These functions were applied on the dimensions of the Czech population. Comparing the classification success of the reference and the tested Czech sample showed that females from Czech population were significantly overestimated and mostly misclassified as males. Overall accuracy of sex assessment significantly decreased (53.6-69.7 %), sex bias -29.4-100 %, which is most probably caused by secular trend and the generally high variability of body size. Results indicate that the discriminant functions, developed for skeletal series representing geographically and chronologically diverse populations, are not applicable in current forensic investigations. Finally, implications and recommendations for future research are discussed.

Influence of Guided Waves in Tibia on Non-linear Scattering of Contrast Agents.

PubMed

Wang, Diya; Zhong, Hui; Zhai, Yu; Hu, Hong; Jin, Bowen; Wan, Mingxi

2016-02-01

The aim of this study was to elucidate the linear and non-linear responses of ultrasound contrast agent (UCA) to frequency-dispersive guided waves from the tibia cortex, particularly two individual modes, S0 (1.23 MHz) and A1 (2.06 MHz). The UCA responses to guided waves were illustrated through the Marmottant model derived from measured guided waves, and then verified by continuous infusion experiments in a vessel-tibia flow phantom. These UCA responses were further evaluated by the enhanced ratio of peak values and the resolutions of UCA backscattered echoes. Because of the individual modes S0 and A1 in the tibia, the peak values of the UCA backscattered echoes were enhanced by 83.57 ± 7.35% (p < 0.05) and 80.77 ± 6.60% (p < 0.01) in the UCA subharmonic frequency and subharmonic imaging, respectively. However, corresponding resolutions were 0.78 ± 0.07 (p < 0.05) and 0.72 ± 0.12 (p < 0.01) times those without guided wave disturbances, respectively. Even though the resolution was partly degenerated, the subharmonic detection sensitivity of UCA was improved by the guided waves. Thus, UCA responses to the double-frequency guided waves should be further explored to benefit the detection of capillary perfusion in tissue layers near the bone cortex, particularly for perfusion imaging in the free flaps and skeletal muscles. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

The effect of sol-gel-formed calcium phosphate coatings on bone ingrowth and osteoconductivity of porous-surfaced Ti alloy implants.

PubMed

Nguyen, H Q; Deporter, D A; Pilliar, R M; Valiquette, N; Yakubovich, R

2004-02-01

Ti-6Al-4V implants formed with a sintered porous surface for implant fixation by bone ingrowth were prepared with or without the addition of a thin surface layer of calcium phosphate (Ca-P) formed using a sol-gel coating technique over the porous surface. The implants were placed transversely across the tibiae of 17 rabbits. Implanted sites were allowed to heal for 2 weeks, after which specimens were retrieved for morphometric assessment using backscattered scanning electron microscopy and quantitative image analysis. Bone formation along the porous-structured implant surface, was measured in relation to the medial and lateral cortices as an indication of implant surface osteoconductivity. The Absolute Contact Length measurements of endosteal bone growth along the porous-surfaced zone were greater with the Ca-P-coated implants compared to the non-Ca-P-coated implants. The Ca-P-coated implants also displayed a trend towards a significant increase in the area of bone ingrowth (Bone Ingrowth Fraction). Finally, there was significantly greater bone-to-implant contact within the sinter neck regions of the Ca-P-coated implants.

Comparative Evaluation of Cell Viability Immediately After Osteotomy for Implants With Drills and Piezosurgery: Immunohistochemistry Analysis.

PubMed

Pereira, Cassiano Costa Silva; Batista, Fábio Roberto de Souza; Jacob, Ricardo Garcia Mureb; Nogueira, Lamis Meorin; Carvalho, Abrahão Cavalcante Gomes de Souza; Gealh, Walter Cristiano; Garcia-Júnior, Idelmo Rangel; Okamoto, Roberta

2018-05-08

To evaluate the effect of reusing drills and piezosurgery tips during implant osteotomy on immediate bone cell viability through immunohistochemical analysis. Six male rabbits were divided into 2 groups and then divided into 5 subgroups-correspond to drills and tips used 10, 20, 30, 40, and 50 times, respectively. All animals received 10 osteotomies in each tibia, by use of the classic drilling procedure in one group (G1) and the piezosurgery device in the other group (G2). For immunohistochemical technique were utilized the osteoprotegerin, RANKL, osteocalcin, and caspase 3. Control procedures were performed by omitting the primary antibodies (negative control). Bone formation and resorption responses presented in more intense way during the piezosurgery. The expression of osteocalcin had become quite intense in piezosurgery groups, but with reduced immunostaining from the 30th osteotomy. The caspase 3 showed the viability of the osteoblast from the 20th osteotomy with piezosurgery and remained constant until the 50th. Piezosurgery provides greater osteoblastic cell viability than the system of conventional drilling. This study will provide data so that the authors can recycle the drills and tips for implant placement, thus enabling a better cell viability for osseointegration.

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.

Sinus Microanatomy and Microbiota in a Rabbit Model of Rhinosinusitis

PubMed Central

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

2018-01-01

Background: Rabbits are useful for preclinical studies of sinusitis because of similar physiologic features to humans. The objective of this study is to develop a rabbit model of sinusitis that permits assessment of microanatomy and sampling for evaluating shifts in the sinus microbiota during the development of sinusitis and to test how the mucociliary clearance (MCC) defect might lead to dysbiosis and chronic rhinosinusitis (CRS). Methods: Generation of CRS was accomplished with an insertion of a sterile sponge into the left middle meatus of New Zealand white rabbits (n = 9) for 2 weeks. After sponge removal, 4 rabbits were observed for another 10 weeks and evaluated for CRS using endoscopy, microCT, visualization of the functional micro-anatomy by micro-optical coherence tomography (μOCT), and histopathological analysis of the sinus mucosa. Samples were taken from the left middle meatus and submitted for microbiome analysis. Results: CT demonstrated opacification of all left sinuses at 2 weeks in all rabbits (n = 9), which persisted in animals followed for another 12 weeks (n = 4). Histology at week 2 showed mostly neutrophils. On week 14, significant infiltration of plasma cells and lymphocytes was noted with increased submucosal glands compared to controls (p = 0.02). Functional microanatomy at 2 weeks showed diminished periciliary layer (PCL) depth (p < 0.0001) and mucus transport (p = 0.0044) compared to controls despite a thick mucus layer. By 12 weeks, the thickened mucus layer was resolved but PCL depletion persisted in addition to decreased ciliary beat frequency (CBF; p < 0.0001). The mucin fermenting microbes (Lactobacillales, Bacteroidales) dominated on week 2 and there was a significant shift to potential pathogens (e.g., Pseudomonas, Burkholderia) by week 14 compared to both controls and the acute phase (p < 0.05). Conclusion: We anticipate this reproducible model will provide a means for identifying underlying mechanisms of airway-surface liquid (ASL) depletion and fundamental changes in sinus microbial communities that contribute to the development of CRS. The rabbit model of sinusitis exhibited diminished PCL depth with delayed mucus transport and significant alterations and shift in the sinus microbiome during the development of chronic inflammation. PMID:29376039

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.

Bioactivity of sol-gel-derived TiO2 coating on polyetheretherketone: In vitro and in vivo studies.

PubMed

Shimizu, Takayoshi; Fujibayashi, Shunsuke; Yamaguchi, Seiji; Yamamoto, Koji; Otsuki, Bungo; Takemoto, Mitsuru; Tsukanaka, Masako; Kizuki, Takashi; Matsushita, Tomiharu; Kokubo, Tadashi; Matsuda, Shuichi

2016-04-15

A polyetheretherketone (PEEK) surface was modified using a sol-gel-derived TiO2 coating in order to confer bone-bonding ability. To enhance the bonding strength of the coating layer, pretreatment with either O2 plasma or sandblasting was performed prior to sol-gel coating. Additionally, post-treatment with acid was carried out to confer apatite (calcium phosphate)-forming ability to the surface. Biomechanical and histological analyses performed using an in vivo rabbit tibia model showed that PEEK surfaces modified with sol-gel-derived TiO2 and acid post-treatment had better bone-bonding properties than uncoated PEEK surfaces. These modified surfaces also performed well in terms of their in vitro cell responses due to their modified surface chemistries and topographies. Although O2 plasma or sandblasting treatment were, for the most part, equivocal in terms of performance, we conclude that sol-gel-derived TiO2 coating followed by acid post-treatment significantly improves the bone bonding ability of PEEK surfaces, thus rendering them optimal for their use in surgical implants. The role of polyetheretherketone (PEEK) as an alternative biomaterial to conventional metallic implant materials has become increasingly important. However, its low bone bonding ability is yet to be resolved. This in vivo and in vitro investigation on the functionalization of PEEK surfaces highlights the utility of this material in clinical interventions that require implants, and may extend range of applications of PEEK. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. 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

Bone pulsating metastasis due to renal cell carcinoma.

PubMed

Cınar, Murat; Derincek, Alihan; Karan, Belgin; Akpınar, Sercan; Tuncay, Cengiz

2010-11-01

Pulsation on the bone cortex surface is a rare condition. Pulsative palpation of the superficial-located bone tumors can be misperceived as an aneurysm. Fifty-eight-year-old man is presented with pulsating bone mass in his proximal tibia. During angiographic examination, hypervascular masses were diagnosed both at right kidney and at right proximal tibia. Renal cell carcinoma was diagnosed after abdominal CT scan. Proximal tibia biopsy was complicated with projectile bleeding.

Multiple Tibial Insufficiency Fractures in the Same Tibia

PubMed Central

Defoort, Saartje; Mertens, Peter

2011-01-01

Stress fractures were first described by Briethaupt in 1855. Since then, there have been many discussions in the literature concerning stress fractures, which have been described in both weight-bearing and non-weight-bearing bones. Currently, the tibia is the most frequent location, but multiple stress fractures in the same tibia are rare. This paper presents an unusual case of a 60-year-old woman with multiple tibial stress fractures of spontaneous onset. PMID:23569673

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

Comparison of 3D bone models of the knee joint derived from CT and 3T MR imaging.

PubMed

Neubert, Aleš; Wilson, Katharine J; Engstrom, Craig; Surowiec, Rachel K; Paproki, Anthony; Johnson, Nicholas; Crozier, Stuart; Fripp, Jurgen; Ho, Charles P

2017-08-01

To examine whether magnetic resonance (MR) imaging can offer a viable alternative to computed tomography (CT) based 3D bone modeling. CT and MR (SPACE, TrueFISP, VIBE) images were acquired from the left knee joint of a fresh-frozen cadaver. The distal femur, proximal tibia, proximal fibula and patella were manually segmented from the MR and CT examinations. The MR bone models obtained from manual segmentations of all three sequences were compared to CT models using a similarity measure based on absolute mesh differences. The average absolute distance between the CT and the various MR-based bone models were all below 1mm across all bones. The VIBE sequence provided the best agreement with the CT model, followed by the SPACE, then the TrueFISP data. The most notable difference was for the proximal tibia (VIBE 0.45mm, SPACE 0.82mm, TrueFISP 0.83mm). The study indicates that 3D MR bone models may offer a feasible alternative to traditional CT-based modeling. A single radiological examination using the MR imaging would allow simultaneous assessment of both bones and soft-tissues, providing anatomically comprehensive joint models for clinical evaluation, without the ionizing radiation of CT imaging. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

A potential means of improving the evaluation of deformity corrections with Taylor spatial frames over time by using volumetric imaging: preliminary results.

PubMed

Starr, Vanessa; Olivecrona, H; Noz, M E; Maguire, G Q; Zeleznik, M P; Jannsson, Karl-åke

2009-01-01

In this study we explore the possibility of accurately and cost-effectively monitoring tibial deformation induced by Taylor Spatial Frames (TSFs), using time-separated computed tomography (CT) scans and a volume fusion technique to determine tibial rotation and translation. Serial CT examinations (designated CT-A and CT-B, separated by a time interval of several months) of two patients were investigated using a previously described and validated volume fusion technique, in which user-defined landmarks drive the 3D registration of the two CT volumes. Both patients had undergone dual osteotomies to correct for tibial length and rotational deformity. For each registration, 10 or more landmarks were selected, and the quality of the fused volume was assessed both quantitatively and via 2D and 3D visualization tools. First, the proximal frame segment and tibia in CT-A and CT-B were brought into alignment (registered) by selecting landmarks on the frame and/or tibia. In the resulting "fused" volume, the proximal frame segment and tibia from CT-A and CT-B were aligned, while the distal frame segment and tibia from CT-A and CT-B were likely not aligned as a result of tibial deformation or frame adjustment having occurred between the CT scans. Using the proximal fused volume, the distal frame segment and tibia were then registered by selecting landmarks on the frame and/or tibia. The difference between the centroids of the final distal landmarks was used to evaluate the lengthening of the tibia, and the Euler angles from the registration were used to evaluate the rotation. Both the frame and bone could be effectively registered (based on visual interpretation). Movement between the proximal frame and proximal bone could be visualized in both cases. The spatial effect on the tibia could be both visually assessed and measured: 34 mm, 10 degrees in one case; 5 mm, 1 degrees in the other. This retrospective analysis of spatial correction of the tibia using Taylor Spatial Frames shows that CT offers an interesting potential means of quantitatively monitoring the patient's treatment. Compared with traditional techniques, modern CT scans in conjunction with image processing provide a high-resolution, spatially correct, and three-dimensional measurement system which can be used to quickly and easily assess the patient's treatment at low cost to the patient and hospital.

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.

Repeated irradiation from micro-computed tomography scanning at 2, 4 and 6 months of age does not induce damage to tibial bone microstructure in male and female CD-1 mice.

PubMed

Sacco, Sandra M; Saint, Caitlin; Longo, Amanda B; Wakefield, Charles B; Salmon, Phil L; LeBlanc, Paul J; Ward, Wendy E

2017-01-01

Long-term effects of repeated i n vivo micro-computed tomography (μCT) scanning at key stages of growth and bone development (ages 2, 4 and 6 months) on trabecular and cortical bone structure, as well as developmental patterns, have not been studied. We determined the effect of repetitive μCT scanning at age 2, 4 and 6 months on tibia bone structure of male and female CD-1 mice and characterized developmental changes. At 2, 4 and 6 months of age, right tibias were scanned using in vivo μCT (Skyscan 1176) at one of three doses of radiation per scan: 222, 261 or 460 mGy. Left tibias of the same mice were scanned only at 6 months to serve as non-irradiated controls to determine whether recurrent radiation exposure alters trabecular and cortical bone structure at the proximal tibia. In males, eccentricity was lower ( P <0.05) in irradiated compared with non-irradiated tibias (222 mGy group). Within each sex, all other structural outcomes were similar between irradiated and non-irradiated tibias regardless of dose. Trabecular bone loss occurred in all mice due to age while cortical development continued to age 6 months. In conclusion, repetitive μCT scans at various radiation doses did not damage trabecular or cortical bone structure of proximal tibia in male and female CD-1 mice. Moreover, scanning at 2, 4 and 6 months of age highlight the different developmental time course between trabecular and cortical bone. These scanning protocols can be used to investigate longitudinal responses of bone structures to an intervention.

Fatigue Failure in Extra-Articular Proximal Tibia Fractures: Locking Intramedullary Nail Versus Double Locking Plates-A Biomechanical Study.

PubMed

Kandemir, Utku; Herfat, Safa; Herzog, Mary; Viscogliosi, Paul; Pekmezci, Murat

2017-02-01

The goal of this study is to compare the fatigue strength of a locking intramedullary nail (LN) construct with a double locking plate (DLP) construct in comminuted proximal extra-articular tibia fractures. Eight pairs of fresh frozen cadaveric tibias with low bone mineral density [age: 80 ± 7 (SD) years, T-score: -2.3 ± 1.2] were used. One tibia from each pair was fixed with LN, whereas the contralateral side was fixed with DLP for complex extra-articular multifragmentary metaphyseal fractures (simulating OTA 41-A3.3). Specimens were cyclically loaded under compression simulating single-leg stance by staircase method out to 260,000 cycles. Every 2500 cycles, localized gap displacements were measured with a 3D motion tracking system, and x-ray images of the proximal tibia were acquired. To allow for mechanical settling, initial metrics were calculated at 2500 cycles. The 2 groups were compared regarding initial construct stiffness, initial medial and lateral gap displacements, stiffness at 30,000 cycles, medial and lateral gap displacements at 30,000 cycles, failure load, number of cycles to failure, and failure mode. Failure metrics were reported for initial and catastrophic failures. DLP constructs exhibited higher initial stiffness and stiffness at 30,000 cycles compared with LN constructs (P < 0.03). There were no significant differences between groups for loads at failure or cycles to failure. For the fixation of extra-articular proximal tibia fractures, a LN provides a similar fatigue performance to double locked plates. The locked nail could be safely used for fixation of proximal tibia fractures with the advantage of limited extramedullary soft tissue damage.

Fibular fixation as an adjuvant to tibial intramedullary nailing in the treatment of combined distal third tibia and fibula fractures: a biomechanical investigation.

PubMed

Morin, Paul M; Reindl, Rudolf; Harvey, Edward J; Beckman, Lorne; Steffen, Thomas

2008-02-01

Distal third tibia fractures have classically been treated with standard plating, but intramedullary (IM) nailing has gained popularity. Owing to the lack of interference fit of the nail in the metaphyseal bone of the distal tibia, it may be beneficial to add rigid plating of the fibula to augment the overall stability of fracture fixation in this area. This study sought to assess the biomechanical effect of adding a fibular plate to standard IM nailing in the treatment of distal third tibia and fibula fractures. Eight cadaveric tibia specimens were used. Tibial fixation consisted of a solid titanium nail locked with 3 screws distally and 2 proximally, and fibular fixation consisted of a 3.5 mm low-contact dynamic compression plate. A section of tibia and fibula was removed. Testing was accomplished with an MTS machine. Each leg was tested 3 times; with and without a fibular plate and with a repetition of the initial test condition. Vertical displacements were tested with an axial load up to 500 N, and angular rotation was tested with torques up to 5 N*m. The difference in axial rotation was the only statistically significant finding (p = 0.003), with fibular fixation resulting in 1.1 degrees less rotation through the osteotomy site (17.96 degrees v. 19.10 degrees ). Over 35% of this rotational displacement occurred at the nail-locking bolt interface with the application of small torsional forces. Fibular plating in addition to tibial IM fixation of distal third tibia and fibula fractures leads to slightly increased resistance to torsional forces. This small improvement may not be clinically relevant.

Genetic determinism of bone and mineral metabolism in meat-type chickens: A QTL mapping study.

PubMed

Mignon-Grasteau, Sandrine; Chantry-Darmon, Céline; Boscher, Marie-Yvonne; Sellier, Nadine; Chabault-Dhuit, Marie; Le Bihan-Duval, Elisabeth; Narcy, Agnès

2016-12-01

Skeletal integrity in meat-type chickens is affected by many factors including rapid growth rate, nutrition and genetics. To investigate the genetic basis of bone and mineral metabolism, a QTL detection study was conducted in an intercross between two lines of meat-type chickens divergently selected for their high (D +) or low (D -) digestive efficiency. Tibia size (length, diameter, volume) and ash content were determined at 3 weeks of age as well as phosphorus (P) retention and plasma concentration. Heritability of these traits and their genetic correlations with digestive efficiency were estimated. A QTL mapping study was performed using 3379 SNP markers. Tibia size, weight, ash content and breaking strength were highly heritable (0.42 to 0.61). Relative tibia diameter and volume as well as P retention were strongly and positively genetically correlated with digestive efficiency (0.57 to 0.80). A total of 35 QTL were identified (9 for tibia weight, 13 for tibia size, 5 for bone strength, 5 for bone mineralization, 2 for plasma P concentration and 1 for P retention). Six QTL were genome-wide significant, and 3 QTL for tibia relative volume, weight and ash weight on chromosome 6 were fixed, the positive allele coming from the D-line. For two QTL for ash content on chromosome 18 and relative tibia length on chromosome 26, the confidence intervals were small enough to identify potential candidate genes. These findings support the evidence of multiple genetic loci controlling bone and mineral metabolism. The identification of candidate genes may provide new perspectives in the understanding of bone regulation, even beyond avian species.

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.

A comparison of models of the isometric force of locust skeletal muscle in response to pulse train inputs.

PubMed

Wilson, Emma; Rustighi, Emiliano; Newland, Philip L; Mace, Brian R

2012-03-01

Muscle models are an important tool in the development of new rehabilitation and diagnostic techniques. Many models have been proposed in the past, but little work has been done on comparing the performance of models. In this paper, seven models that describe the isometric force response to pulse train inputs are investigated. Five of the models are from the literature while two new models are also presented. Models are compared in terms of their ability to fit to isometric force data, using Akaike's and Bayesian information criteria and by examining the ability of each model to describe the underlying behaviour in response to individual pulses. Experimental data were collected by stimulating the locust extensor tibia muscle and measuring the force generated at the tibia. Parameters in each model were estimated by minimising the error between the modelled and actual force response for a set of training data. A separate set of test data, which included physiological kick-type data, was used to assess the models. It was found that a linear model performed the worst whereas a new model was found to perform the best. The parameter sensitivity of this new model was investigated using a one-at-a-time approach, and it found that the force response is not particularly sensitive to changes in any parameter.

Infection Reduces Return-to-duty Rates for Soldiers with Type III Open Tibia Fractures

DTIC Science & Technology

2014-09-01

Infection reduces return-to-duty rates for soldiers with Type III open tibia fractures Matthew A. Napierala, MD, Jessica C. Rivera, MD, Travis C... Type III open tibia fracture and tabulated the prevalence of infectious complications.We searched the Physical Evaluation Board database to determine...were not infected ( p 0.1407). Soldiers who experienced any type of infectious complication ( p 0.0470) and having osteomyelitis ( p 0.0335) had a lower

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

Analysis of anatomic periarticular tibial plate fit on normal adults.

PubMed

Goyal, Kanu S; Skalak, Anthony S; Marcus, Randall E; Vallier, Heather A; Cooperman, Daniel R

2007-08-01

Implant manufacturers are producing anatomically contoured periarticular plates to improve the treatment of proximal tibia fractures. We assessed the accuracy of the designation anatomic. We applied eight-hole medial and lateral anatomically contoured periarticular plates to 101 cadaveric tibiae. The tibiae and the plate fits were mapped, quantified, and analyzed using a MicroScribe G2LX digitizer, Rhinoceros software, and MATLAB software. By corresponding the clinical appearance of good fit with our digital findings, we created numerical criteria for plate fit in three planes: coronal (volume of free space between the plate and bone), sagittal (alignment with the tibial plateau and shaft), and axial (match in curvature between the proximal horizontal part of the plate and the tibial plateau). An anatomic fit should mirror the shape of the tibia in all three planes, and only four medial and four lateral plate fits qualified. Recognizing and understanding the substantial variations in fit that exist between anatomically contoured plates and the tibia may help lead to a more stable fixation and prevent malreduction of the fracture and/or soft tissue impingement.

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

Noninvasive Raman spectroscopy of rat tibiae: approach to in vivo assessment of bone quality

PubMed Central

Okagbare, Paul I.; Begun, Dana; Tecklenburg, Mary; Awonusi, Ayorinde; Goldstein, Steven A.

2012-01-01

Abstract. We report on in vivo noninvasive Raman spectroscopy of rat tibiae using robust fiber-optic Raman probes and holders designed for transcutaneous Raman measurements in small animals. The configuration allows placement of multiple fibers around a rat leg, maintaining contact with the skin. Bone Raman data are presented for three regions of the rat tibia diaphysis with different thicknesses of overlying soft tissue. The ability to perform in vivo noninvasive Raman measurement and evaluation of subtle changes in bone composition is demonstrated with rat leg phantoms in which the tibia has carbonated hydroxylapatite, with different carbonate contents. Our data provide proof of the principle that small changes in bone composition can be monitored through soft tissue at anatomical sites of interest in biomedical studies. PMID:23085899

Noninvasive Raman spectroscopy of rat tibiae: approach to in vivo assessment of bone quality.

PubMed

Okagbare, Paul I; Begun, Dana; Tecklenburg, Mary; Awonusi, Ayorinde; Goldstein, Steven A; Morris, Michael D

2012-09-01

We report on in vivo noninvasive Raman spectroscopy of rat tibiae using robust fiber-optic Raman probes and holders designed for transcutaneous Raman measurements in small animals. The configuration allows placement of multiple fibers around a rat leg, maintaining contact with the skin. Bone Raman data are presented for three regions of the rat tibia diaphysis with different thicknesses of overlying soft tissue. The ability to perform in vivo noninvasive Raman measurement and evaluation of subtle changes in bone composition is demonstrated with rat leg phantoms in which the tibia has carbonated hydroxylapatite, with different carbonate contents. Our data provide proof of the principle that small changes in bone composition can be monitored through soft tissue at anatomical sites of interest in biomedical studies.

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

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.

Mechanical loading, damping, and load-driven bone formation in mouse tibiae.

PubMed

Dodge, Todd; Wanis, Mina; Ayoub, Ramez; Zhao, Liming; Watts, Nelson B; Bhattacharya, Amit; Akkus, Ozan; Robling, Alexander; Yokota, Hiroki

2012-10-01

Mechanical loads play a pivotal role in the growth and maintenance of bone and joints. Although loading can activate anabolic genes and induce bone remodeling, damping is essential for preventing traumatic bone injury and fracture. In this study we investigated the damping capacity of bone, joint tissue, muscle, and skin using a mouse hindlimb model of enhanced loading in conjunction with finite element modeling to model bone curvature. Our hypothesis was that loads were primarily absorbed by the joints and muscle tissue, but that bone also contributed to damping through its compression and natural bending. To test this hypothesis, fresh mouse distal lower limb segments were cyclically loaded in axial compression in sequential bouts, with each subsequent bout having less surrounding tissue. A finite element model was generated to model effects of bone curvature in silico. Two damping-related parameters (phase shift angle and energy loss) were determined from the output of the loading experiments. Interestingly, the experimental results revealed that the knee joint contributed to the largest portion of the damping capacity of the limb, and bone itself accounted for approximately 38% of the total phase shift angle. Computational results showed that normal bone curvature enhanced the damping capacity of the bone by approximately 40%, and the damping effect grew at an accelerated pace as curvature was increased. Although structural curvature reduces critical loads for buckling in beam theory, evolution apparently favors maintaining curvature in the tibia. Histomorphometric analysis of the tibia revealed that in response to axial loading, bone formation was significantly enhanced in the regions that were predicted to receive a curvature-induced bending moment. These results suggest that in addition to bone's compressive damping capacity, surrounding tissues, as well as naturally-occurring bone curvature, also contribute to mechanical damping, which may ultimately affect bone remodeling and bone quality. Copyright © 2012 Elsevier Inc. All rights reserved.

[Intramedullary nailing of the tibia with the expert tibia nail].

PubMed

Hansen, Matthias; El Attal, René; Blum, Jochen; Blauth, Michael; Rommens, Pol Maria

2009-12-01

Restoration of axis, length, and rotation of the lower leg. Sufficient primary stability of the osteosynthesis for functional aftercare. Early functional aftercare to maintain joint mobility. Good bony healing in closed and open fractures. All closed and open fractures of the tibia and complete lower leg fractures (AO 42). Certain extraarticular fractures of the proximal and distal tibia (AO 41 A2/A3; AO 43 A1/A2/A3). Segmental fractures of the tibia. Certain intraarticular fractures of the tibia with use of additional implants (AO 41 C1/C2; AO 43 C1/C2). Stabilization during and after segmental bone transport or callus distraction of the tibia. Patients in poor general condition (e.g., bedridden). Flexion of the knee of less than 90 degrees . Infection in the nail's insertion area. Infection of the tibial cavity. Complex articular fractures of the proximal or distal tibia with joint depression. Closed reduction of the fracture. If necessary, use of reduction clamps through additional stab incisions or open surgical procedures. In some cases, additional osteosynthesis procedures are necessary (e.g., screws). Positioning of the patient may be performed on a radiolucent table or a traction table. Opening of the proximal tibia in line with the medullary canal. Cannulated or noncannulated insertion of the Expert Tibia Nail((R)) with or without reaming of the medullary canal depending on the fracture type and soft-tissue condition. Control of axis, length, and rotation. Distal interlocking with the radiolucent drill and proximal interlocking with the targeting device. Immediate mobilization of ankle joint and knee joint. Depending on the type of fracture, mobilization with 20 kg partial weight bearing or pain-dependent full weight bearing with crutches. X-ray control 6 weeks postoperatively and increased weight bearing depending on the fracture status. In a prospective, international multicentric study, 181 patients with 186 fractures were included between July 2004 and May 2005. 57 of these fractures (30.7%) initially were graded open, 15 of them grade I, 32 grade II, and ten grade III. Most of the fractures (36%) were shaft fractures. After 1 year, 146 patients (81%) could be evaluated clinically and radiologically. The overall pseudarthrosis rate was 12.2% (18.2% for open and 9.7% for closed fractures). The risk for secondary operations or revisions (including dynamization of the nail) was 18.8%. Without consideration of dynamization procedures, revisions were necessary in only 5.4% of all patients. The risk for varus, valgus or antecurvation malalignment of more than 5 degrees in any plane on radiologic long leg views was 4.3% for shaft fractures, 1.5% for distal fractures, and 13.6% for proximal fractures. The implant-specific risk for bolt breakage was 3.2%.

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

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 Roughly Focused Extracorporeal Shock Waves Therapy on the Expressions of Bone Morphogenetic Protein-2 and Osteoprotegerin in Osteoporotic Fracture in Rats

PubMed Central

Huang, Hai-Ming; Li, Xiao-Lin; Tu, Shu-Qiang; Chen, Xiao-Feng; Lu, Chang-Chun; Jiang, Liang-Hua

2016-01-01

Background: Roughly focused extracorporeal shock waves therapy (ESWT) is characterized by a wide focal area, a large therapy zone, easy positioning, and less pain during treatment. The purpose of this study was to investigate the effects of roughly focused ESWT on the expression of osteoprotegerin (OPG) and bone morphogenetic protein-2 (BMP-2) in osteoporotic fractures in rats. Methods: Seventy-two female Sprague-Dawley (SD) rats, 3 months old, were divided into sham-operated group (n = 6) and an ovariectomized (OVX) group (n = 66). Sixty OVX SD rats were used as a model of double proximal tibial osteotomy and inner fixation. The osteotomy site in the left tibia was treated with roughly focused ESWT once at an energy density of 0.26 mJ/mm2, 60 doses/min, and 2000 pact quantities. The contralateral right tibia was left untreated and served as a control. Expression of OPG and BMP-2 in the callus of the osteoporotic fracture area was assessed using immunohistochemistry, real-time polymerase chain reaction (PCR), and Western blotting analysis. Results: Bone mineral density (BMD) at the proximal tibia, femur, and L5 spine was significantly reduced after ovariectomy. BMD of proximal tibia was 12.9% less in the OVX group than that in the sham-operated group. Meanwhile, bilateral oophorectomy resulted in a lower trabecular bone volume fraction (BV/TV) in the proximal tibia of the sham-OVX animals. Three months after bilateral oophorectomy, BV/TV was 14.29% of baseline BV/TV in OVX legs versus 45.91% in the sham-OVX legs (P < 0.001). These data showed that the SD rats became a suitable model of osteoporosis, 3 months after they were OVX. Immunohistochemical analysis showed higher levels of BMP-2 and OPG expression in the treatment group than those in the control group. Compared with the contralateral controls, decreased expression of OPG and BMP-2 at 3 days after roughly focused ESWT, followed by a later increase at 7 days, was indicated by real-time PCR and Western blotting analysis. The OPG messenger RNA (mRNA) expression levels peaked at 6 weeks after the shock wave treatment, paired with a much earlier (at 4 weeks) increase of BMP-2, and declined close to normal at 8 weeks. Conclusions: Roughly focused ESWT may promote the expression of OPG and BMP-2 in the osteoporotic fracture area in rats. BMP-2 and OPG may act synergistically and may lead to a significant enhancement of bone formation and remodeling. PMID:27779163

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

Rats and rabbits as pharmacokinetic screening tools for long acting intramuscular depots: case study with paliperidone palmitate suspension.

PubMed

Patel, Harilal; Patel, Prakash; Modi, Nirav; Patel, Pinakin; Wagh, Yogesh; George, Alex; Desai, Nirmal; Srinivas, Nuggehally R

2018-05-08

Development of prodrug of 9-hydroxyrisperidone (paliperidone) long-acting intramuscular injection has enabled delivery over four-week time period with improved compliance. The key aim of this work was to establish a reliable preclinical model which may potentially serve as a screening tool for judging the pharmacokinetics of paliperidone formulation(s) prior to human clinical work. Sparse sampling composite study was used in rats, (Wistar/Sprague-Dawley (SD; n = 10)) and a serial blood sampling study design was used in rabbits (n = 4). Animals received intramuscular injection of paliperidone palmitate in the thigh muscle at dose of 16 (rats) and 4.5 mg/kg (rabbits). Samples were drawn in rats (retro-orbital sinus) and rabbits (central ear artery) and were analysed for paliperidone using liquid chromatography-mass spectrometry/ mass spectrometry (LC-MS/MS) assay. The plasma data was subjected to pharmacokinetic analysis. Following intramuscular injection of depot formulation in Wistar/SD rats and rabbits, absorption of paliperidone was slow and gradual with median value of time to reach maximum concentration (T max ) occurring on day 7. The exposures (i.e. area under the curve (AUC; 0-28) days) were 18,597, 21,865 and 18,120 ng.h/mL, in Wistar, SD and rabbits, respectively. The clearance was slow and supported long half-life (8-10 days). Either one of the two models can serve as a research tool for establishing pharmacokinetics of paliperidone formulation(s).

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.

Electrical stimulation at the dorsal root ganglion preserves trabecular bone mass and microarchitecture of the tibia in hindlimb-unloaded rats.

PubMed

Lau, Y-C; Qian, X; Po, K-T; Li, L-M; Guo, X

2015-02-01

This study seeks to investigate the effect of electrical stimulation (ES) at dorsal root ganglion (DRG) on disuse bone loss in a rat model. Hindlimb unloading for 14 days resulted in significant bone loss in rat tibia while rats with ES at DRG showed a significant reduced bone loss Mechanical unloading induces osteoporosis in both human and animals. Previous studies demonstrated that electrical stimulation (ES) to dorsal root ganglion (DRG) could trigger secretion of calcitonin gene-related peptide (CGRP) which plays an important role in bone modeling and remodeling. This study seeks to investigate the effect of ES to DRG on disuse bone loss in a rat model. Twenty-four rats were randomly assigned in three experimental groups: cage control (CC), hindlimb unloading (HU), and hindlimb unloading with ES (HUES). ES was applied via implantable micro-electrical stimulators (IMES) to right DRGs at vertebral levels L4-L6 in HUES group. Hindlimb unloading for 14 days resulted in 25.9% decrease in total bone mineral content (BMC), 29.2% decrease in trabecular BMD and trabecular microarchitecture and connectivity were significantly deteriorated in the proximal tibia metaphysis in HU group, while rats with ES at DRG showed significant reduced bone loss that there was 3.8% increase in total BMC, 2.3% decrease in trabecular BMD, and significant improvement in trabecular microarchitecture. There was a concurrent enhancement of expression of CGRP in stimulated DRGs. The results confirm the effect of ES at DRG on enhancing CGRP expression and suggest potential applications of IMES for the prevention and treatment of disuse bone loss.

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.

Evaluation of functional outcome of the floating knee injury using multivariate analysis.

PubMed

Yokoyama, Kazuhiko; Tsukamoto, Tatsuro; Aoki, Shinichi; Wakita, Ryuji; Uchino, Masataka; Noumi, Takashi; Fukushima, Nobuaki; Itoman, Moritoshi

2002-11-01

The objective of this study is to evaluate significant contributing factors affecting the functional prognosis of floating knee injuries using multivariate analysis. A total of 68 floating knee injuries (67 patients) were treated at Kitasato University Hospital from 1986 to 1999. Both the femoral fractures and the tibial fractures were managed surgically by various methods. The functional results of these injuries were evaluated using the grading system of Karlström and Olerud. Follow-up periods ranged from 2 to 19 years (mean 50.2 months) after the original injury. We defined satisfactory (S) outcomes as those cases with excellent or good results and unsatisfactory (US) outcomes as those cases with acceptable or poor results. Logistic regression analysis was used as a multivariate analysis, and the dependent variables were defined as a satisfactory outcome or as an unsatisfactory outcome. The explanatory variables were predicting factors influencing the functional outcome such as age at trauma, gender, severity of soft-tissue injury in the femur and the tibia, AO fracture grade in the femur and the tibia, Fraser type (type I or type II), Injury Severity Score (ISS), and fixation time after injury (less than 1 week or more than 1 week) in the femur and the tibia. The final functional results were as follows: 25 cases had excellent results, 15 cases good results, 16 cases acceptable results, and 12 cases poor results. The predictive logistic regression equation was as follows: Log 1-p/p = 3.12-1.52 x Fraser type - 1.65 x severity of soft-tissue injury in the tibia - 1.31 x fixation time after injury in the tibia - 0.821 x AO fracture grade in the tibia + 1.025 x fixation time after injury in the femur - 0.687 x AO fracture grade in the femur ( p=0.01). Among the variables, Fraser type and the severity of soft-tissue injury in the tibia were significantly related to the final result. The multivariate analysis showed that both the involvement of the knee joint and the severity grade of soft-tissue injury in the tibia represented significant risk factors of poor outcome in floating knee injuries in this study.

Tibia and radius bone geometry and volumetric density in obese compared to non-obese adolescents.

PubMed

Leonard, Mary B; Zemel, Babette S; Wrotniak, Brian H; Klieger, Sarah B; Shults, Justine; Stallings, Virginia A; Stettler, Nicolas

2015-04-01

Childhood obesity is associated with biologic and behavioral characteristics that may impact bone mineral density (BMD) and structure. The objective was to determine the association between obesity and bone outcomes, independent of sexual and skeletal maturity, muscle area and strength, physical activity, calcium intake, biomarkers of inflammation, and vitamin D status. Tibia and radius peripheral quantitative CT scans were obtained in 91 obese (BMI>97th percentile) and 51 non-obese adolescents (BMI>5th and <85th percentiles). Results were converted to sex- and race-specific Z-scores relative to age. Cortical structure, muscle area and muscle strength (by dynamometry) Z-scores were further adjusted for bone length. Obese participants had greater height Z-scores (p<0.001), and advanced skeletal maturity (p<0.0001), compared with non-obese participants. Tibia cortical section modulus and calf muscle area Z-scores were greater in obese participants (1.07 and 1.63, respectively, both p<0.0001). Tibia and radius trabecular and cortical volumetric BMD did not differ significantly between groups. Calf muscle area and strength Z-scores, advanced skeletal maturity, and physical activity (by accelerometry) were positively associated with tibia cortical section modulus Z-scores (all p<0.01). Adjustment for muscle area Z-score attenuated differences in tibia section modulus Z-scores between obese and non-obese participants from 1.07 to 0.28. After multivariate adjustment for greater calf muscle area and strength Z-scores, advanced maturity, and less moderate to vigorous physical activity, tibia section modulus Z-scores were 0.32 (95% CI -0.18, 0.43, p=0.06) greater in obese, vs. non-obese participants. Radius cortical section modulus Z-scores were 0.45 greater (p=0.08) in obese vs. non-obese participants; this difference was attenuated to 0.14 with adjustment for advanced maturity. These findings suggest that greater tibia cortical section modulus in obese adolescents is attributable to advanced skeletal maturation and greater muscle area and strength, while less moderate to vigorous physical activities offset the positive effects of these covariates. The impact of obesity on cortical structure was greater at weight bearing sites. Copyright © 2014 Elsevier Inc. All rights reserved.

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

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.

A longitudinal study of bone area, content, density, and strength development at the radius and tibia in children 4-12 years of age exposed to recreational gymnastics.

PubMed

Jackowski, S A; Baxter-Jones, A D G; Gruodyte-Raciene, R; Kontulainen, S A; Erlandson, M C

2015-06-01

This study investigated the long-term relationship between the exposure to childhood recreational gymnastics and bone measures and bone strength parameters at the radius and tibia. It was observed that individuals exposed to recreational gymnastics had significantly greater total bone content and area at the distal radius. No differences were observed at the tibia. This study investigated the relationship between exposure to early childhood recreational gymnastics with bone measures and bone strength development at the radius and tibia. One hundred twenty seven children (59 male, 68 female) involved in either recreational gymnastics (gymnasts) or other recreational sports (non-gymnasts) between 4 and 6 years of age were recruited. Peripheral quantitative computed tomography (pQCT) scans of their distal and shaft sites of the forearm and leg were obtained over 3 years, covering the ages of 4-12 years at study completion. Multilevel random effects models were constructed to assess differences in the development of bone measures and bone strength measures between those exposed and not exposed to gymnastics while controlling for age, limb length, weight, physical activity, muscle area, sex, and hours of training. Once age, limb length, weight, muscle area, physical activity, sex, and hours of training effects were controlled, it was observed that individuals exposed to recreational gymnastics had significantly greater total bone area (18.0 ± 7.5 mm(2)) and total bone content (6.0 ± 3.0 mg/mm) at the distal radius (p < 0.05). This represents an 8-21 % benefit in ToA and 8-15 % benefit to ToC from 4 to 12 years of age. Exposure to recreational gymnastics had no significant effect on bone measures at the radius shaft or at the tibia (p > 0.05). Exposure to early life recreational gymnastics provides skeletal benefits to distal radius bone content and area. Thus, childhood recreational gymnastics exposure may be advantageous to bone development at the wrist.

Dairy product intake and bone properties in 70-year-old men and women.

PubMed

Hallkvist, Olle M; Johansson, Jonas; Nordström, Anna; Nordström, Peter; Hult, Andreas

2018-01-29

In the present population-based study including 70-year-old men and women, total dairy product intake was associated with a weak positive association with tibia trabecular and cortical cross-sectional areas. Milk consumption has recently been suggested to increase fracture risk. Therefore, we aimed to investigate associations between dairy product consumption and peripheral bone properties. Furthermore, we explored whether consumption of milk and fermented dairy products affected bone properties differently. The Healthy Aging Initiative is a population-based, cross-sectional study investigating the health of 70-year-old men and women. Out of the 2904 individuals who met the inclusion criteria, data on self-reported daily dairy product consumption (dl/day), peripheral quantitative computed tomography (pQCT) examinations at the 4 and 66% scan sites of the tibia and radius, and dual-energy X-ray absorptiometry (DXA) scans were collected from 2040 participants. Associations between dairy product consumption and bone properties were examined using multiple linear regression models adjusted for sex, muscle area, meal size, dietary protein proportion, current smoking status, and objectively measured physical activity. Total dairy product intake was associated with larger trabecular (2.296 (95% CI, 0.552-4.039) mm 2 , per dl/day increase, p = 0.01) and cortical cross-sectional areas (CSAs) in the tibia (1.757 (95% CI, 0.683-2.830 mm 2 , p = 0.001) as measured by pQCT and higher areal bone mineral density (aBMD) of the radius (3.231 (95% CI, 0.764-5.698) mg/cm 2 , p = 0.01) as measured by DXA. No other measurement in the tibia, radius, femoral neck, or lower spine was associated significantly with dairy product intake. Bone properties did not differ according to the type of dairy product consumed. No evidence of a negative association between dairy product consumption and bone health was found. Furthermore, total dairy product consumption was associated with increased CSAs in the tibia, regardless of dairy product type. Collectively, our findings indicate the existence of a weak but significant positive association between dairy product consumption bone properties in older adults.

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.

Maxillary sinus floor elevation using BMP-2 and Nell-1 gene-modified bone marrow stromal cells and TCP in rabbits.

PubMed

Xia, Lunguo; Xu, Yuanjin; Chang, Qing; Sun, Xiaojuan; Zeng, Deliang; Zhang, Wenjie; Zhang, Xiuli; Zhang, Zhiyuan; Jiang, Xinquan

2011-07-01

This study evaluated the synergistic osteogenic effect of bone morphogenetic protein-2 (BMP-2) and Nel-like molecule-1 (Nell-1) genes in a rabbit maxillary sinus floor elevation model. Bone marrow stromal cells (bMSCs) were cultured and transduced with AdEGFP, AdNell-1, AdBMP-2, or AdNell-1 + AdBMP-2 overexpression virus. These gene-modified autologous bMSCs were then combined with a β-tricalcium phosphate (β-TCP) granule scaffold and used to elevate the maxillary sinus floor in rabbits. bMSCs cotransduced with AdNell-1 + AdBMP-2 demonstrated a synergistic effect on osteogenic differentiation as detected by real-time PCR analysis on markers of runt-related transcription factor-2, osteocalcin, collagen type 1, alkaline phosphatase activity, and calcium deposits in vitro. As for maxillary sinus floor elevation in a rabbit model in vivo, AdNell-1 + AdBMP-2 gene-transduced autologeous bMSCs/β-TCP complex had the largest bone area and most mature bone structure among the groups, as detected by HE staining and immunohistochemistry at weeks 2 and 8 after implantation. Our data suggested that the BMP-2 and Nell-1 genes possessed a synergistic effect on osteogenic differentiation of bMSCs, while bMSCs modified with the BMP-2 and Nell-1 genes could promote new bone formation and maturation in the rabbit maxillary sinus model.

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

Bone mineral properties in growing Col1a2(+/G610C) mice, an animal model of osteogenesis imperfecta.

PubMed

Masci, Marco; Wang, Min; Imbert, Laurianne; Barnes, Aileen M; Spevak, Lyudmila; Lukashova, Lyudmila; Huang, Yihe; Ma, Yan; Marini, Joan C; Jacobsen, Christina M; Warman, Matthew L; Boskey, Adele L

2016-06-01

The Col1a2(+/G610C) knock-in mouse, models osteogenesis imperfecta in a large old order Amish family (OOA) with type IV OI, caused by a G-to-T transversion at nucleotide 2098, which alters the gly-610 codon in the triple-helical domain of the α2(I) chain of type I collagen. Mineral and matrix properties of the long bones and vertebrae of male Col1a2(+/G610C) and their wild-type controls (Col1a2(+/+)), were characterized to gain insight into the role of α2-chain collagen mutations in mineralization. Additionally, we examined the rescuability of the composition by sclerostin inhibition initiated by crossing Col1a2(+/G610C) with an LRP(+/A214V) high bone mass allele. At age 10-days, vertebrae and tibia showed few alterations by micro-CT or Fourier transform infrared imaging (FTIRI). At 2-months-of-age, Col1a2(+/G610C) tibias had 13% fewer secondary trabeculae than Col1a2(+/+), these were thinner (11%) and more widely spaced (20%) than those of Col1a2(+/+) mice. Vertebrae of Col1a2(+/G610C) mice at 2-months also had lower bone volume fraction (38%), trabecular number (13%), thickness (13%) and connectivity density (32%) compared to Col1(a2+/+). The cortical bone of Col1a2(+/G610C) tibias at 2-months had 3% higher tissue mineral density compared to Col1a2(+/+); Col1a2(+/G610C) vertebrae had lower cortical thickness (29%), bone area (37%) and polar moment of inertia (38%) relative to Col1a2(+/+). FTIRI analysis, which provides information on bone chemical composition at ~7μm-spatial resolution, showed tibias at 10-days did not differ between genotypes. Comparing identical bone types in Col1a2(+/G610C) to Col1a2(+/+) at 2-months-of-age, tibias showed higher mineral-to-matrix ratio in trabeculae (17%) and cortices (31%). and in vertebral cortices (28%). Collagen maturity was 42% higher at 10-days-of-age in Col1a2(+/G610C) vertebral trabeculae and in 2-month tibial cortices (12%), vertebral trabeculae (42%) and vertebral cortices (12%). Higher acid-phosphate substitution was noted in 10-day-old trabecular bone in vertebrae (31%) and in 2-month old trabecular bone in both tibia (31%) and vertebrae (4%). There was also a 16% lower carbonate-to-phosphate ratio in vertebral trabeculae and a correspondingly higher (22%) carbonate-to-phosphate ratio in 2month-old vertebral cortices. At age 3-months-of-age, male femurs with both a Col1a2(+/G610C) allele and a Lrp5 high bone mass allele (Lrp5+/A214V) showed an improvement in bone composition, presenting higher trabecular carbonate-to-phosphate ratio (18%) and lower trabecular and cortical acid-phosphate substitutions (8% and 18%, respectively). Together, these results indicate that mutant collagen α2(I) chain affects both bone quantity and composition, and the usefulness of this model for studies of potential OI therapies such as anti-sclerostin treatments. Copyright © 2016 Elsevier Inc. All rights reserved.

Bone Mineral Properties in Growing Col1a2+/G610C Mice, an animal model of Osteogenesis Imperfecta

PubMed Central

Masci, Marco; Wang, Min; Imbert, Laurianne; Barnes, Aileen M; Spevak, Lyudmila; Lukashova, Lyudmila; Yihe, Huang; Yan, Ma; Marini, Joan C; Jacobsen, Christina M; Warman, Matthew L; Boskey, Adele L

2016-01-01

The Col1a2+/G610C knock-in mouse, models osteogenesis imperfecta in a large old order Amish family (OOA) with type IV OI, caused by a G-to-T transversion at nucleotide 2098, which alters the gly-610 codon in the triple-helical domain of the α2(I) chain of type I collagen. Mineral and matrix properties of the long bones and vertebrae of male Col1a2+/G610C and their wild-type controls (Col1a2+/+), were characterized to gain insight into the role of α2-chain collagen mutations in mineralization. Additionally, we examined the rescuability of the composition by sclerostin inhibition initiated by crossing Col1a2+/G610C with an LRP+/A214V high bone mass allele. At age 10-days, vertebrae and tibia showed few alterations by micro-CT or Fourier transform infrared imaging (FTIRI). At 2-months-of-age, Col1a2+/G610C tibias had 13% fewer secondary trabeculae than Col1a2+/+, these were thinner (11%) and more widely spaced (20%) than those of Col1a2+/+ mice. Vertebrae of Col1a2+/G610C mice at 2-months also had lower bone volume fraction (38%), trabecular number (13%), thickness (13%) and connectivity density (32%) compared to Col1a2+/+. The cortical bone of Col1a2+/G610C tibias at 2-months had 3% higher tissue mineral density compared to Col1a2+/+; Col1a2+/G610C vertebrae had lower cortical thickness (29%), bone area (37%) and polar moment of inertia (38%) relative to Col1a2+/+. FTIRI analysis, which provides information on bone chemical composition at ~ 7 µm-spatial resolution, showed tibias at 10-days, did not differ between genotypes. Comparing identical bone types in Col1a2+/G610C to Col1a2+/+ at 2-months-of-age, tibias showed higher mineral-to-matrix ratio in trabeculae (17%) and cortices (31%). and in vertebral cortices (28%). Collagen maturity was 42% higher at 10-days-of-age in Col1a2+/G610C vertebral trabeculae and in 2-month tibial cortices (12%), vertebral trabeculae (42%) and vertebral cortices (12%). Higher acid-phosphate substitution was noted in 10-day-old trabecular bone in vertebrae (31%) and in 2-month old trabecular bone in both tibia (31%) and vertebrae (4%). There was also a 16% lower carbonate-to-phosphate ratio in vertebral trabeculae and a correspondingly higher (22%) carbonate-to-phosphate ratio in 2 month-old vertebral cortices. At age 3- months-of-age, male femurs with both a Col1a2+/G610C allele and a Lrp5 high bone mass allele (Lrp5+/A214V) showed an improvement in bone composition, presenting higher trabecular carbonate-to-phosphate ratio (18%) and lower trabecular and cortical acid-phosphate substitutions (8% and 18%, respectively). Together, these results indicate that mutant collagen α2(I) chain affects both bone quantity and composition, and the usefulness of this model for studies of potential OI therapies such as anti-sclerostin treatments. PMID:27083399

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

Bisphosphonate-ciprofloxacin bound to Skelite is a prototype for enhancing experimental local antibiotic delivery to injured bone.

PubMed

Buxton, T B; Walsh, D S; Harvey, S B; McPherson, J C; Hartmann, J F; Plowman, K M

2004-09-01

The risk of osteomyelitis after open bone fracture may be reduced by locally applied antibiotics. ENC-41-HP (E41), which comprises ciprofloxacin linked to a 'bone seeking' bisphosphonate, loaded on to carrier Skelite calcium phosphate granules (E41-Skelite) has favourable in vitro characteristics for application to wounded bone. This study assessed E41-Skelite in a rat model of acute tibial osteomyelitis. Mechanically induced tibial troughs were contaminated with approximately log10 4 colony forming units (c.f.u.) of Staphylococcus aureus (Cowan 1 strain) 'resistant' to E41 (minimum inhibitory concentration 8-16 microg/ml), lavaged and packed with Skelite alone, or with E41-Skelite slurry. Animals were killed at 24 h (n = 62), 72 h (n = 46) or 14 days (n = 12), and each tibia was assessed for S. aureus load (c.f.u./g tibia) and histological appearance (14 days only). At 24 and 72 h, the tibias of rats treated with E41-Skelite (n = 54) had a significantly lower mean (s.e.m.) load of S. aureus than animals that received Skelite alone (n = 54): log10 3.6(0.2) versus 6.4(0.1) c.f.u./g respectively at 24 h (P < 0.001, Mann-Whitney rank sum test) and log10 4.4(0.2) versus 6.6(0.1) c.f.u./g at 72 h (P < 0.001). At 14 days, E41-Skelite-treated tibias had fewer bacteria, no signs of osteomyelitis and histological signs of healing. E41-Skelite, a prototype granulated topical antibiotic delivery system, reduced the development of infection in experimental bone wounds. Copyright 2004 British Journal of Surgery Society Ltd.

Sagittal plane kinematics of passive dorsiflexion of the foot in adolescent athletes.

PubMed

Gatt, Alfred; Chockalingam, Nachiappan; Falzon, Owen

2013-01-01

Although assessment of passive maximum foot dorsiflexion angle is performed routinely, there is a paucity of information regarding adolescents' foot and foot segment motion during this procedure. There are currently no trials investigating the kinematics of the adolescent foot during passive foot dorsiflexion. A six-camera optoelectronic motion capture system was used to collect kinematic data using the Oxford Foot Model. Eight female amateur gymnasts 11 to 16 years old (mean age, 13.2 years; mean height, 1.5 m) participated in the study. A dorsiflexing force was applied to the forefoot until reaching maximum resistance with the foot placed in the neutral, pronated, and supinated positions in random order. The maximum foot dorsiflexion angle and the range of movement of the forefoot to hindfoot, tibia to forefoot, and tibia to hindfoot angles were computed. Mean ± SD maximum foot dorsiflexion angles were 36.3° ± 7.2° for pronated, 36.9° ± 4.0° for neutral, and 33.0° ± 4.9° for supinated postures. One-way repeated-measures analysis of variance results were nonsignificant among the 3 groups (P = .70), as were the forefoot to tibia angle and hindfoot to tibia angle variations (P = .091 and P = .188, respectively). Forefoot to hindfoot angle increased with the application of force, indicating that in adolescents, the forefoot does not lock at any particular posture as portrayed by the traditional Rootian paradigm. Participants had very flexible foot dorsiflexion, unlike those in another study assessing adolescent athletes. This finding, together with nonsignificant statistical results, implies that foot dorsiflexion measurement may be performed at any foot posture without notably affecting results.

Tissue Reaction to a Novel Bone Substitute Material Fabricated With Biodegradable Polymer-Calcium Phosphate Nanoparticle Composite.

PubMed

Shimizu, Hideo; Jinno, Yohei; Ayukawa, Yasunori; Atsuta, Ikiru; Arahira, Takaaki; Todo, Mitsugu; Koyano, Kiyoshi

2016-10-01

The aim of this study was to evaluate the effectiveness of a novel bone substitute material fabricated using a biodegradable polymer-calcium phosphate nanoparticle composite. Porous structured poly-L-lactic acid (PLLA) and hydroxyapatite (HA) nanoparticle composite, which was fabricated using solid-liquid phase separation and freeze-drying methods, was grafted into bone defects created in rat calvarium or tibia. Rats were killed 4 weeks after surgery, and histological analyses were performed to evaluate new bone formation. Scanning electron microscopic observation showed the interconnecting pores within the material and the pore diameter was approximately 100 to 300 μm. HA nanoparticles were observed to be embedded into the PLLA beams. In the calvarial implantation model, abundant blood vessels and fibroblastic cells were observed penetrating into pores, and in the tibia model, newly formed bone was present around and within the composite. The PLLA-HA nanoparticle composite bone substitute developed in this study showed biocompatibility, elasticity, and operability and thus has potential as a novel bone substitute.

[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.

Stress fracture as a complication of autogenous bone graft harvest from the distal tibia.

PubMed

Chou, Loretta B; Mann, Roger A; Coughlin, Michael J; McPeake, William T; Mizel, Mark S

2007-02-01

Autogenous bone graft from the distal tibia provides cancellous bone graft for foot and ankle operations, and it has osteogenic and osteoconductive properties. The site is in close proximity to the foot and ankle, and published retrospective studies show low morbidity from the procedure. One-hundred autografts were obtained from the distal tibia between 2000 and 2003. In four cases the distal tibial bone graft harvest resulted in a stress fracture. There were three women and one man. The average time of diagnosis of the stress fracture from the operation was 1.8 months. All stress fractures healed with a short course (average 2.4 months) of cast immobilization. This study demonstrated that a stress fracture from the donor site of autogenous bone graft of the distal tibia occurs and can be successfully treated nonoperatively.

Novel implant for peri-prosthetic proximal tibia fractures.

PubMed

Tran, Ton; Chen, Bernard K; Wu, Xinhua; Pun, Chung Lun

2018-03-01

Repair of peri-prosthetic proximal tibia fractures is very challenging in patients with a total knee replacement or arthroplasty. The tibial component of the knee implant severely restricts the fixation points of the tibial implant to repair peri-prosthetic fractures. A novel implant has been designed with an extended flange over the anterior of tibial condyle to provide additional points of fixation, overcoming limitations of existing generic locking plates used for proximal tibia fractures. Furthermore, the screws fixed through the extended flange provide additional support to prevent the problem of subsidence of tibial component of knee implant. The design methodology involved extraction of bone data from CT scans into a flexible CAD format, implant design and structural evaluation and optimisation using FEM as well as prototype development and manufacture by selective laser melting 3D printing technology with Ti6Al4 V powder. A prototype tibia implant was developed based on a patient-specific bone structure, which was regenerated from the CT images of patient's tibia. The design is described in detail and being applied to fit up to 80% of patients, for both left and right sides based on the average dimensions and shape of the bone structure from a wide range of CT images. A novel tibial implant has been developed to repair peri-prosthetic proximal tibia fractures which overcomes significant constraints from the tibial component of existing knee implant. Copyright © 2018 Elsevier Ltd. All rights reserved.

Limb saving surgery for Ewing's sarcoma of the distal tibia: a case report.

PubMed

Mizoshiri, Naoki; Shirai, Toshiharu; Terauchi, Ryu; Tsuchida, Shinji; Mori, Yuki; Katsuyama, Yusei; Hayashi, Daichi; Oka, Yoshinobu; Kubo, Toshikazu

2018-05-02

Ewing's sarcoma is a primary malignant tumor of bone occurring mostly in childhood. Few effective reconstruction techniques are available after wide resection of Ewing's sarcoma at the distal end of the tibia. Reconstruction after wide resection is especially difficult in children, as it is necessary to consider the growth and activity of the lower limbs. A 12-year-old Japanese boy had presented with right lower leg pain at age 8 years. Imaging examination showed a bone tumor accompanied by a large extra-skeletal mass in the distal part of his tibia. The tumor was histologically diagnosed as Ewing's sarcoma. The patient received chemotherapy, followed by wide resection. Reconstruction consisted of a bone transport method involving external fixation of Taylor Spatial Frame. To prevent infection after surgery, the external fixation pin was coated with iodine. One year after surgery, the patient showed poor consolidation of bone, so iliac bone transplantation was performed on the extended bones and docking site of the distal tibia. After 20 months, tibia formation was good. Three years after surgery, there was no evidence of tumor recurrence or metastases; bone fusion was good, and he was able to run. The bone transport method is an effective surgical method of reconstruction after wide resection of a bone tumor at the distal end of the tibia, if a pin can be inserted into the distal bone fragment. Coating external fixation pins with iodine may prevent postoperative infection.

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...

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.

Principal component analysis in construction of 3D human knee joint models using a statistical shape model method.

PubMed

Tsai, Tsung-Yuan; Li, Jing-Sheng; Wang, Shaobai; Li, Pingyue; Kwon, Young-Min; Li, Guoan

2015-01-01

The statistical shape model (SSM) method that uses 2D images of the knee joint to predict the three-dimensional (3D) joint surface model has been reported in the literature. In this study, we constructed a SSM database using 152 human computed tomography (CT) knee joint models, including the femur, tibia and patella and analysed the characteristics of each principal component of the SSM. The surface models of two in vivo knees were predicted using the SSM and their 2D bi-plane fluoroscopic images. The predicted models were compared to their CT joint models. The differences between the predicted 3D knee joint surfaces and the CT image-based surfaces were 0.30 ± 0.81 mm, 0.34 ± 0.79 mm and 0.36 ± 0.59 mm for the femur, tibia and patella, respectively (average ± standard deviation). The computational time for each bone of the knee joint was within 30 s using a personal computer. The analysis of this study indicated that the SSM method could be a useful tool to construct 3D surface models of the knee with sub-millimeter accuracy in real time. Thus, it may have a broad application in computer-assisted knee surgeries that require 3D surface models of the knee.

Comparison of morphological changes in efferent lymph nodes after implantation of resorbable and non-resorbable implants in rabbits

PubMed Central

2011-01-01

Background Magnesium alloys as biodegradable implant materials received much interest in recent years. It is known that products of implant degradation can induce several types of immune response. Hence, the aim of this study was to examine the morphological changes of efferent lymph nodes after implantation of different resorbable magnesium alloys (MgCa0.8, LAE442) in comparison to commercially available resorbable (PLA) and non-resorbable (titanium) implant materials as well as control groups without implant material. Methods The different implant materials were inserted intramedullary into the rabbit tibia. After postoperative observation periods of three and six months, popliteal lymph nodes were examined histologically and immunhistologically and compared to lymph nodes of sham operated animals and animals without surgery. Haematoxylin and eosin staining was performed for cell differentiation. Mouse anti-CD79α and rat anti-CD3 monoclonal primary antibodies were used for B- and T-lymphocyte detection, mouse anti-CD68 primary antibodies for macrophage detection. Evaluation of all sections was performed applying a semi quantitative score. Results The histological evaluation demonstrated low and moderate levels of morphological changes for both magnesium alloys (LAE442 and MgCa0.8). Higher than moderate values were reached for titanium in sinus histiocytosis and histiocytic apoptosis (3 months) and for PLA in histiocytic apoptosis (3 and 6 months). The immune response to all investigated implants had a non-specific character and predominantly was a foreign-body reaction. LAE442 provoked the lowest changes which might be due to a lower degradation rate in comparison to MgCa0.8. Therewith it is a promising candidate for implants with low immunogenic potential. Conclusion Both examined magnesium alloys did not cause significantly increased morphological changes in efferent lymph nodes in comparison to the widely used implant materials titanium and PLA. LAE442 induced even lower immunological reactions. Therewith MgCa0.8 and especially LAE442 are appropriate candidates for biomedical use. PMID:21521497

Effects of Local and Systemic Zoledronic Acid Application on Titanium Implant Osseointegration: An Experimental Study Conducted on Two Surface Types.

PubMed

Dundar, Serkan; Yaman, Ferhan; Gecor, Orhan; Cakmak, Omer; Kirtay, Mustafa; Yildirim, Tuba Talo; Karaman, Tahir; Benlidayi, Mehmet Emre

2017-06-01

The aim of this study was to evaluate the effects of local and systemic zoledronic acid (ZA) applications on titaniumoksit ceramic blasted (TiO-CB)- and sandblasted large acid-grit (SLA)-surfaced titanium implant osseointegration. Twelve New Zealand White rabbits were used in the study, divided into 6 groups: the TiO-CB (TiO-CB-CNT) (n = 2) and SLA (SLA-CNT) (n = 2) control groups in which TiO-CB- and SLA-surfaced titanium implants were surgically inserted into rabbit tibias but no treatment was applied; the TiO-CB (TiO-CB-LZA) (n = 2) and SLA (SLA-LZA) (n = 2) local ZA groups in which 1 mL of normal saline solution containing 2 mg of ZA was injected into sockets and after this the implants were integrated; and the TiO-CB (TiO-CB-SZA) (n = 2) and SLA (SLA-SZA) (n = 2) systemic ZA groups in which a single infusion of 0.1 mg/kg of ZA was administered during surgical implant insertion. Following a period of osseointegration, bone implant contact (BIC) was recorded as a proportion of the total implant surface length in direct contact with the bone. Results of this study indicate that BIC was greater in the systemic ZA application groups than in the local ZA application groups, and BIC was greater in the local ZA groups than in the controls. Statistically significant differences in BIC were not detected between the TiO-CB- and SLA-surfaced implants in all the groups. Furthermore, this study did not reveal significant differences between the 2 types of surfaces due to similar average roughness values. Overall, systemic ZA application was found to be more effective in increasing BIC than local ZA application based on the results obtained by testing 2 implant surfaces.

In vivo response of bioactive PMMA-based bone cement modified with alkoxysilane and calcium acetate.

PubMed

Sugino, Atsushi; Ohtsuki, Chikara; Miyazaki, Toshiki

2008-11-01

The use of polymethylmethacrylate (PMMA)-based bone cement is popular in orthopedics for the fixation of artificial joints with bone. However, it has a major problem with prostheses loosening because of coverage by fibrous tissue after long-term implantation. Recently, a bioactive bone cement has been developed that shows direct bonding to living bone through modification of PMMA resin with gamma-methacryloxypropyltrimethoxysilane (MPS) and calcium acetate. The cement is designed to exhibit bioactivity, through incorporation of silanol groups and calcium ions. Thus, it has the potential to form a layer of bone-like hydroxyapatite, which is essential for achieving direct bonding to living bone. This type of modification allows the cement to show spontaneous hydroxyapatite formation on its surface in a simulated body fluid after one day, and there is evidence of osteoconduction of the cement in rabbit tibia for periods of more than three weeks. However, the influence of the dissolved ions from the modified cement has not yet been clarified. Thus, the authors focused on the dissolution of the modified PMMA-based bone cement and its tissue response in muscle and bone by comparison with the behavior of non-modified PMMA-based bone cement. One week after implantation in the latissimus dorsi of a rabbit, the modified PMMA-based bone cement showed more inflammatory width than the commercial cement. However, four weeks after implantation, the inflammatory width of both cements was essentially the same. The osteoconductivity around the modified cement was higher than that for the conventional cement after four weeks implantation. These results indicate that the initial dissolution of calcium acetate from the modified cement to form the hydroxyapatite induced the acute inflammation around tissue, but also developed the osteoconductivity. It is suggested that the initial inflammation can be effective for inducing osteoconduction through a bone healing reaction when the material provides an environment that promotes bone formation.

Repeatability testing of a new Hybrid III 6-year-old ATD lower extremity.

PubMed

Boucher, Laura C; Ryu, Yeonsu; Kang, Yun-Seok; Bolte, John H

2017-05-29

Vehicle safety is improving, thus decreasing the number of life-threatening injuries and increasing the need for research in other areas of the body. The current child anthropomorphic test device (ATD) does not have the capabilities or instrumentation to measure many of the potential interactions between the lower extremity and the vehicle interior. A prototype Hybrid III 6-year-old ATD lower extremity (ATD-LE) was developed and contains a tibia load cell and a more biofidelic ankle. The repeatability of the device has not yet been assessed; thus, the objective was to evaluate the repeatability of the ATD-LE. Additionally, a dynamic assessment was conducted to quantify injury threshold values. A pneumatic ram impactor was used at 2 velocities to evaluate repeatability. The ATD-LE was fixed to a table and impacted on the plantar aspect of the forefoot. Three repeated trials at 1.3 and 2.3 m/s without shoes and 2.3 m/s with shoes were conducted. The consistency of tibia force (N), bending moment (Nm), ankle range of motion (ROM, °), and stiffness (Nm/°) were quantified. A dynamic assessment using knee bolster airbag (KBA) tests was also conducted. The ATD-LE was positioned to mimic 3 worst-case scenarios: toes touching the mid-dashboard, touching the lower dashboard, and flat on the floor prior to airbag deployment. The impact responses in the femur and tibia were directly collected and compared with published injury threshold values. Ram impact testing indicated primarily excellent repeatability for the variables tested. For all 3 conditions the coefficients of variance (CV) were as follows: tibia force, 1.9-2.7%; tibia moment, 1.0-2.2%; ROM, 1.3-1.4%; ankle stiffness, 4.8-15.6%. The shoe-on condition resulted in a 25% reduction in tibia force and a 56% reduction in tibia bending moment. The KBA tests indicate that the highest injury risk may be when the toes touch the lower dashboard, due to the high bending moments recorded in the tibia at 76.2 Nm, which was above the injury threshold. The above work has demonstrated that the repeatability of the ATD-LE was excellent for tibia force, bending moment, and ankle ROM. The ATD-LE has the ability to provide new information to engineers and researchers due to its ability to directly evaluate the crash response of the ankle and leg. New information on injury mechanism and injury tolerance may lead to injury reduction and thus help advance the safety of children.

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.

Allograft-prosthesis composites after bone tumor resection at the proximal tibia.

PubMed

Biau, David Jean; Dumaine, Valérie; Babinet, Antoine; Tomeno, Bernard; Anract, Philippe

2007-03-01

The survival of irradiated allograft-prosthesis composites at the proximal tibia is mostly unknown. However, allograft-prosthesis composites have proved beneficial at other reconstruction sites. We presumed allograft-prosthesis composites at the proximal tibia would improve survival and facilitate reattachment of the extensor mechanism compared with that of conventional (megaprostheses) reconstructions. We retrospectively reviewed 26 patients who underwent resection of proximal tibia tumors followed by reconstruction with allo-graft-prosthesis composites. Patients received Guepar massive custom-made fully constrained prostheses. Allografts were sterilized with gamma radiation, and the stems were cemented into the allograft and host bone. The minimum followup was 6 months (median, 128 months; range, 6-195 months). Fourteen patients had one or more components removed. The median allograft-prosthesis composite survival was 102 months (95% confidence interval, 64.2-infinity). Of the 26 allografts, seven fractured, six showed signs of partial resorption, and six had infections develop. Seven allografts showed signs of fusion with the host bone. Six extensor mechanism reconstructions failed. Allograft-prosthesis composites sterilized by gamma radiation yielded poor results for proximal tibial reconstruction as complications and failures were common. We do not recommend irradiated allograft-prosthesis composites for proximal tibia reconstruction.

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

Finite element analysis of unicompartmental knee arthroplasty.

PubMed

Hopkins, Andrew R; New, Andrew M; Rodriguez-y-Baena, Ferdinando; Taylor, Mark

2010-01-01

Concerns over accelerated damage to the untreated compartment of the knee following unicompartmental knee arthroplasty (UKA), as well as the relatively poor success rates observed for lateral as opposed to the medial arthroplasty, remain issues for attention. Finite element analysis (FEA) was used to assess changes to the kinematics and potential for cartilage damage across the knee joint in response to the implantation of the Oxford Mobile Bearing UKA. FE models of lateral and medial compartment arthroplasty were developed, in addition to a healthy natural knee model, to gauge changes incurred through the arthroplasty. Varus-valgus misalignments were introduced to the femoral components to simulate surgical inaccuracy or over-correction. Boundary conditions from the Stanmore knee simulator during the stance phase of level gait were used. AP translations of the tibia in the medial UKA models were comparable to the behaviour of the natural knee models (+/-0.6mm deviation from pre-operative motion). Following lateral UKA, 4.1mm additional posterior translation of the tibia was recorded than predicted for the natural knee. IE rotations of the medial UKA models were less consistent with the pre-operative knee model than the lateral UKA models (7.7 degrees vs. 3.6 degrees deviation). Varus misalignment of the femoral prosthesis was more influential than valgus for medial UKA kinematics, whereas in lateral UKA, a valgus misalignment of the femoral prosthesis was most influential on the kinematics. Resection of the cartilage in the medial compartment reduced the overall risk of progressive OA in the knee, whereas removing the cartilage from the lateral compartment, and in particular introducing a valgus femoral misalignment, increased the overall risk of progressive OA in the knee. Based on these results, under the conditions tested herein, both medial and lateral UKA can be said to induce kinematics of the knee which could be considered broadly comparable to those of the natural knee, and that even a 10 degrees varus-valgus misalignment of the femoral component may not induce highly irregular kinematics. However, elevated posterior translation of the tibia in lateral UKA and large excursions of the insert may explain the higher incidence of bearing dislocation observed in some clinical studies. (c) 2009 IPEM. All rights reserved.

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