Science.gov

Sample records for humanized anti-vegf rabbit

  1. Combination of anti-VEGF therapy and temozolomide in two experimental human glioma models.

    PubMed

    Grossman, Rachel; Brastianos, Harry; Blakeley, Jaishri O; Mangraviti, Antonella; Lal, Bachchu; Zadnik, Patti; Hwang, Lee; Wicks, Robert T; Goodwin, Rory C; Brem, Henry; Tyler, Betty

    2014-01-01

    Anti-angiogenic agents, such as bevacizumab (BEV), can induce normalization of the blood brain barrier, which may influence the penetration and activity of a co-administered cytotoxic drug. However, it is unknown whether this effect is associated with a benefit in overall survival. This study employed intracranial human glioma models to evaluate the effect of BEV alone and in combination with temozolomide (TMZ) and/or radiation therapy (XRT) on overall survival. One hundred eight male athymic rats were intracranially injected with either U251 or U87 human glioma. Ten or eleven days after tumor inoculation, animals bearing U251 and U87, respectively, were treated with: TMZ alone (50 mg/kg for 5 consecutive days, P.O.), BEV alone (15 mg/kg, I.V.), a combination of TMZ and BEV, or a combination of TMZ, BEV, and a single fraction of XRT (20 Gy). Controls received no treatment. The U87 experiment was repeated and the relationship between survival and the extent of anti-angiogenesis via anti-laminin antibodies for the detection of blood vessels was assessed. In both U87 glioma experiments, all of the treatment groups had a statistically significant increase in survival as compared to the control groups. Also, for both U87 experiments the combination groups of TMZ and BEV had significantly better survival when compared to either treatment administered alone, with 75% of animals demonstrating long-term survival (LTS) (defined as animals alive 120 days after tumor implantation) in one experiment and 25% LTS in the repeat experiment. In the U251 glioma experiment, all treated groups (except BEV alone) had significantly improved survival as compared to controls with minimal statistical variance among groups. The percent vessel area was lowest in the group of animals treated with BEV alone. The addition of BEV to TMZ and/or XRT had variable effect on prolonging survival in the two human glioma models tested with reduced tumor vascularity in groups treated with BEV. These

  2. Safety profiles of anti-VEGF drugs: bevacizumab, ranibizumab, aflibercept and ziv-aflibercept on human retinal pigment epithelium cells in culture

    PubMed Central

    Malik, Deepika; Tarek, Mohamed; Caceres del Carpio, Javier; Ramirez, Claudio; Boyer, David; Kenney, M Cristina; Kuppermann, Baruch D

    2014-01-01

    Purpose To compare the safety profiles of antivascular endothelial growth factor (VEGF) drugs ranibizumab, bevacizumab, aflibercept and ziv-aflibercept on retinal pigment epithelium cells in culture. Methods Human retinal pigment epithelium cells (ARPE-19) were exposed for 24 h to four anti-VEGF drugs at 1/2×, 1×, 2× and 10× clinical concentrations. Cell viability and mitochondrial membrane potential assay were performed to evaluate early apoptotic changes and rate of overall cell death. Results Cell viability decreased at 10× concentrations in bevacizumab (82.38%, p=0.0001), aflibercept (82.68%, p=0.0002) and ziv-aflibercept (77.25%, p<0.0001), but not at lower concentrations. However, no changes were seen in cell viability in ranibizumab-treated cells at all concentrations including 10×. Mitochondrial membrane potential was slightly decreased in 10× ranibizumab-treated cells (89.61%, p=0.0006) and 2× and 10× aflibercept-treated cells (88.76%, 81.46%; p<0.01, respectively). A larger reduction in mitochondrial membrane potential was seen at 1×, 2× and 10× concentrations of bevacizumab (86.53%, 74.38%, 66.67%; p<0.01) and ziv-aflibercept (73.50%, 64.83% and 49.65% p<0.01) suggestive of early apoptosis at lower doses, including the clinical doses. Conclusions At clinical doses, neither ranibizumab nor aflibercept produced evidence of mitochondrial toxicity or cell death. However, bevacizumab and ziv-aflibercept showed mild mitochondrial toxicity at clinically relevant doses. PMID:24836865

  3. Discontinuation of anti-VEGF cancer therapy promotes metastasis through a liver revascularization mechanism.

    PubMed

    Yang, Yunlong; Zhang, Yin; Iwamoto, Hideki; Hosaka, Kayoko; Seki, Takahiro; Andersson, Patrik; Lim, Sharon; Fischer, Carina; Nakamura, Masaki; Abe, Mitsuhiko; Cao, Renhai; Skov, Peter Vilhelm; Chen, Fang; Chen, Xiaoyun; Lu, Yongtian; Nie, Guohui; Cao, Yihai

    2016-09-01

    The impact of discontinuation of anti-VEGF cancer therapy in promoting cancer metastasis is unknown. Here we show discontinuation of anti-VEGF treatment creates a time-window of profound structural changes of liver sinusoidal vasculatures, exhibiting hyper-permeability and enlarged open-pore sizes of the fenestrated endothelium and loss of VE-cadherin. The drug cessation caused highly leaky hepatic vasculatures permit tumour cell intravasation and extravasation. Discontinuation of an anti-VEGF antibody-based drug and sunitinib markedly promotes liver metastasis. Mechanistically, host hepatocyte, but not tumour cell-derived vascular endothelial growth factor (VEGF), is responsible for cancer metastasis. Deletion of hepatocyte VEGF markedly ablates the 'off-drug'-induced metastasis. These findings provide mechanistic insights on anti-VEGF cessation-induced metastasis and raise a new challenge for uninterrupted and sustained antiangiogenic therapy for treatment of human cancers.

  4. Discontinuation of anti-VEGF cancer therapy promotes metastasis through a liver revascularization mechanism

    PubMed Central

    Yang, Yunlong; Zhang, Yin; Iwamoto, Hideki; Hosaka, Kayoko; Seki, Takahiro; Andersson, Patrik; Lim, Sharon; Fischer, Carina; Nakamura, Masaki; Abe, Mitsuhiko; Cao, Renhai; Skov, Peter Vilhelm; Chen, Fang; Chen, Xiaoyun; Lu, Yongtian; Nie, Guohui; Cao, Yihai

    2016-01-01

    The impact of discontinuation of anti-VEGF cancer therapy in promoting cancer metastasis is unknown. Here we show discontinuation of anti-VEGF treatment creates a time-window of profound structural changes of liver sinusoidal vasculatures, exhibiting hyper-permeability and enlarged open-pore sizes of the fenestrated endothelium and loss of VE-cadherin. The drug cessation caused highly leaky hepatic vasculatures permit tumour cell intravasation and extravasation. Discontinuation of an anti-VEGF antibody-based drug and sunitinib markedly promotes liver metastasis. Mechanistically, host hepatocyte, but not tumour cell-derived vascular endothelial growth factor (VEGF), is responsible for cancer metastasis. Deletion of hepatocyte VEGF markedly ablates the ‘off-drug'-induced metastasis. These findings provide mechanistic insights on anti-VEGF cessation-induced metastasis and raise a new challenge for uninterrupted and sustained antiangiogenic therapy for treatment of human cancers. PMID:27580750

  5. 18F-FET MicroPET and MicroMRI for Anti-VEGF and Anti-PlGF Response Assessment in an Orthotopic Murine Model of Human Glioblastoma

    PubMed Central

    Nedergaard, Mette Kjoelhede; Michaelsen, Signe Regner; Urup, Thomas; Broholm, Helle; El Ali, Henrik; Poulsen, Hans Skovgaard; Stockhausen, Marie-Thérése

    2015-01-01

    Background Conflicting data exist for anti-cancer effects of anti-placental growth factor (anti-PlGF) in combination with anti-VEGF. Still, this treatment combination has not been evaluated in intracranial glioblastoma (GBM) xenografts. In clinical studies, position emission tomography (PET) using the radiolabeled amino acid O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) and magnetic resonance imaging (MRI) add complementary but distinct information about glioma growth; however, the value of 18F-FET MicroPET combined with MicroMRI has not been investigated preclinically. Here we examined the use of 18F-FET MicroPET and MicroMRI for evaluation of anti-VEGF and anti-PlGF treatment response in GBM xenografts. Methods Mice with intracranial GBM were treated with anti-VEGF, anti-PlGF + anti-VEGF or saline. Bioluminescence imaging (BLI), 18F-FET MicroPET and T2-weighted (T2w)-MRI were used to follow tumour development. Primary end-point was survival, and tumours were subsequently analysed for Ki67 proliferation index and micro-vessel density (MVD). Further, PlGF and VEGFR-1 expression were examined in a subset of the xenograft tumours and in 13 GBM patient tumours. Results Anti-VEGF monotherapy increased survival and decreased 18F-FET uptake, BLI and MVD, while no additive effect of anti-PlGF was observed. 18F-FET SUVmax tumour-to-brain (T/B) ratio was significantly lower after one week (114±6%, n = 11 vs. 143±8%, n = 13; p = 0.02) and two weeks of treatment (116±12%, n = 8 vs. 190±24%, n = 5; p = 0.02) in the anti-VEGF group as compared with the control group. In contrast, T2w-MRI volume was unaffected by anti-VEGF. Gene expression of PlGF and VEGFR-1 in xenografts was significantly lower than in patient tumours. Conclusion 18F-FET PET was feasible for anti-angiogenic response evaluation and superior to T2w-MRI; however, no additive anti-cancer effect of anti-PlGF and anti-VEGF was observed. Thus, this study supports use of 18F-FET PET for response evaluation in future

  6. Anti-VEGF Treatment Strategies for Wet AMD.

    PubMed

    Kovach, Jaclyn L; Schwartz, Stephen G; Flynn, Harry W; Scott, Ingrid U

    2012-01-01

    Over the past few years, antivascular endothelial growth factor (VEGF) therapy has become a standard treatment for neovascular age-related macular degeneration (AMD). During this time, treatment strategies have evolved from a monthly dosing schedule to individualized regimens. This paper will review the currently available anti-VEGF agents and evidence-based treatment strategies.

  7. Defining response to anti-VEGF therapies in neovascular AMD.

    PubMed

    Amoaku, W M; Chakravarthy, U; Gale, R; Gavin, M; Ghanchi, F; Gibson, J; Harding, S; Johnston, R L; Kelly, S P; Kelly, S; Lotery, A; Mahmood, S; Menon, G; Sivaprasad, S; Talks, J; Tufail, A; Yang, Y

    2015-06-01

    The introduction of anti-vascular endothelial growth factor (anti-VEGF) has made significant impact on the reduction of the visual loss due to neovascular age-related macular degeneration (n-AMD). There are significant inter-individual differences in response to an anti-VEGF agent, made more complex by the availability of multiple anti-VEGF agents with different molecular configurations. The response to anti-VEGF therapy have been found to be dependent on a variety of factors including patient's age, lesion characteristics, lesion duration, baseline visual acuity (VA) and the presence of particular genotype risk alleles. Furthermore, a proportion of eyes with n-AMD show a decline in acuity or morphology, despite therapy or require very frequent re-treatment. There is currently no consensus as to how to classify optimal response, or lack of it, with these therapies. There is, in particular, confusion over terms such as 'responder status' after treatment for n-AMD, 'tachyphylaxis' and 'recalcitrant' n-AMD. This document aims to provide a consensus on definition/categorisation of the response of n-AMD to anti-VEGF therapies and on the time points at which response to treatment should be determined. Primary response is best determined at 1 month following the last initiation dose, while maintained treatment (secondary) response is determined any time after the 4th visit. In a particular eye, secondary responses do not mirror and cannot be predicted from that in the primary phase. Morphological and functional responses to anti-VEGF treatments, do not necessarily correlate, and may be dissociated in an individual eye. Furthermore, there is a ceiling effect that can negate the currently used functional metrics such as >5 letters improvement when the baseline VA is good (ETDRS>70 letters). It is therefore important to use a combination of both the parameters in determining the response.The following are proposed definitions: optimal (good) response is defined as when there

  8. Anti-VEGF Therapy for Retinal Vein Occlusions.

    PubMed

    Campa, Claudio; Alivernini, Giuseppe; Bolletta, Elena; Parodi, Maurizio Battaglia; Perri, Paolo

    2016-01-01

    Retinal vein occlusion (RVO) is the second most common cause of visual loss in the Western World. RVO is usually classified into branch RVO (BRVO) and central RVO (CRVO) according to the anatomical site of the vascular occlusion. The pathogenesis of RVO is not yet fully understood, however an important event is the intraluminal thrombus formation, which is usually secondary to several conditions such as hypertension, hyperlipidemia, diabetes and thrombophilia. The blockage of venous circulation causes an elevation of intraluminal pressure in the capillaries, leading to hemorrhages and leakage of fluid within the retina, increase of interstitial pressure and a consequent reduction of retinal perfusion. Ischemia may develop resulting in secretion of vascular endothelial growth factor (VEGF) that causes further vascular leakage and retinal oedema. VEGF has therefore a leading role in RVO pathogenesis and symptoms. As a consequence use of anti-VEGF agents by intravitreal injections has become very common with the aim to improve the clinical outcomes in these patients. Currently 2 anti-VEGF agents (ranimizumab and aflibercept) have been FDA (Food and Drug Administration) and EMA (European Medicine Agency) approved for the treatment of RVO, while another VEGF inhibitor (bevacizumab) is often used "off-label" in clinical practice. Many treatment regimens have been suggested in the clinical trials with these drugs, as monthly injections or injections when needed, however the ideal regimen has not been defined yet. We conducted a systematic review searching MEDLINE for the following terms: retinal vein occlusion, ranibizumab, bevacizumab, aflibercept, vascular endothelial growth factor, macular oedema. Data were extracted by one author (AG and BE) and checked by a second (BPM, CC). Aim of this article was to review available data for each drug, focusing on their efficacy and safety trying to compare their advantages and limits.

  9. The remote effects of intravitreal anti-VEGF therapy

    PubMed Central

    Balta, F; Merticariu, M; Taban, C; Neculau, G; Merticariu, A; Muresanu, D; Badescu, D; Jinga, V

    2016-01-01

    Objective: To study the effects of intravitreal anti-Vascular Endothelial Growth Factor (VEGF) therapy with Avastin for wet Age-Related Macular Degeneration (AMD) on Benign Prostatic Hyperplasia (BPH)-related symptoms. Methods: An exploratory trial was conducted from August 1, 2013 to February 1, 2014, that included 14 male patients previously diagnosed with BPH, who were aged between 59 and 69 years. The trial was performed in Bucharest and involved two medical institutions: the Clinical Hospital of Eye Emergencies and the “Prof. Dr. Theodor Burghele” Hospital. This prospective study utilized both objective and subjective indicators to analyze the link between intravitreal anti-VEGF therapy for wet AMD and BPH. The evaluations consisted of uroflowmetry and International Prostate Symptom Score (I-PSS) assessments. Results: The maximum flow rate (Qmax) improved by an average of 5.05 ml/ sec in 9 patients, whereas the remaining 5 patients showed a slight decrease in Qmax (mean 1.6 ml/ sec). The I-PSS score improved, with an overall decrease of 1.18 points at follow-up compared to the initial score (mean initial score = 2.42; mean follow-up score = 1.24). Conclusion: The analysis revealed that anti-VEGF therapy for wet AMD had a significant positive effect on all BPH-related symptoms; patients reported improved urinary streams and decreased nocturia. Abbreviations: BPH = benign prostatic hyperplasia, AMD = age-related macular degeneration, VEGF = vascular endothelial growth factor, I-PSS = international prostate symptom score, Qmax = maximum flow rate, TSP-1 = thrombospondin-1, FGF-2 = fibroblast growth factor, mRNA = precursor messenger ribonucleic acid, PSA = prostate-specific antigen, DRE = digital rectal examination, AUR = acute urinary retention, COX2 = cyclooxygenase 2, QoL = quality of life PMID:27928444

  10. The remote effects of intravitreal anti-VEGF therapy.

    PubMed

    Balta, F; Merticariu, M; Taban, C; Neculau, G; Merticariu, A; Muresanu, D; Badescu, D; Jinga, V

    2016-01-01

    Objective: To study the effects of intravitreal anti-Vascular Endothelial Growth Factor (VEGF) therapy with Avastin for wet Age-Related Macular Degeneration (AMD) on Benign Prostatic Hyperplasia (BPH)-related symptoms. Methods: An exploratory trial was conducted from August 1, 2013 to February 1, 2014, that included 14 male patients previously diagnosed with BPH, who were aged between 59 and 69 years. The trial was performed in Bucharest and involved two medical institutions: the Clinical Hospital of Eye Emergencies and the "Prof. Dr. Theodor Burghele" Hospital. This prospective study utilized both objective and subjective indicators to analyze the link between intravitreal anti-VEGF therapy for wet AMD and BPH. The evaluations consisted of uroflowmetry and International Prostate Symptom Score (I-PSS) assessments. Results: The maximum flow rate (Qmax) improved by an average of 5.05 ml/ sec in 9 patients, whereas the remaining 5 patients showed a slight decrease in Qmax (mean 1.6 ml/ sec). The I-PSS score improved, with an overall decrease of 1.18 points at follow-up compared to the initial score (mean initial score = 2.42; mean follow-up score = 1.24). Conclusion: The analysis revealed that anti-VEGF therapy for wet AMD had a significant positive effect on all BPH-related symptoms; patients reported improved urinary streams and decreased nocturia. Abbreviations: BPH = benign prostatic hyperplasia, AMD = age-related macular degeneration, VEGF = vascular endothelial growth factor, I-PSS = international prostate symptom score, Qmax = maximum flow rate, TSP-1 = thrombospondin-1, FGF-2 = fibroblast growth factor, mRNA = precursor messenger ribonucleic acid, PSA = prostate-specific antigen, DRE = digital rectal examination, AUR = acute urinary retention, COX2 = cyclooxygenase 2, QoL = quality of life.

  11. Moving Past Anti-VEGF: Novel Therapies for Treating Diabetic Retinopathy

    PubMed Central

    Bolinger, Mark T.; Antonetti, David A.

    2016-01-01

    Diabetic retinopathy is the leading cause of blindness in working age adults, and is projected to be a significant future health concern due to the rising incidence of diabetes. The recent advent of anti-vascular endothelial growth factor (VEGF) antibodies has revolutionized the treatment of diabetic retinopathy but a significant subset of patients fail to respond to treatment. Accumulating evidence indicates that inflammatory cytokines and chemokines other than VEGF may contribute to the disease process. The current review examines the presence of non-VEGF cytokines in the eyes of patients with diabetic retinopathy and highlights mechanistic pathways in relevant animal models. Finally, novel drug targets including components of the kinin–kallikrein system and emerging treatments such as anti-HPTP (human protein tyrosine phosphatase) β antibodies are discussed. Recognition of non-VEGF contributions to disease pathogenesis may lead to novel therapeutics to enhance existing treatments for patients who do not respond to anti-VEGF therapies. PMID:27618014

  12. Method development to quantify Bv8 expression in circulating CD11b+ cells in patients with neovascular age-related macular degeneration (nvAMD) exhibiting Anti-VEGF refractoriness.

    PubMed

    Catchpole, Timothy; Daniels, Tad; Perkins, Jill; Csaky, Karl G

    2016-07-01

    A subset of neovascular age-related macular degeneration (nvAMD) subjects appears to be refractory to the effects of anti-VEGF treatment and require frequent intravitreal injections. Prokineticin-2 (Bv8) expression in CD11b(+) cells has been linked to anti-VEGF response. We have developed a reproducible method to quantify gene expression in circulating CD11b + cells. Utilizing this method we tested the hypothesis that high Bv8 expression in circulating CD11b(+) cells is associated with anti-VEGF refractoriness in nvAMD patients. Two groups of nvAMD subjects undergoing treatment with anti-VEGF agents were recruited and classified as refractory or non-refractory to anti-VEGF treatment (n = 33 for each group). Two blood draws were obtained from each subject 1-9 months apart. Peripheral blood mononuclear cells (PBMCs) were isolated and CD11b(+) cells were purified via magnetic bead separation. RNA was purified, and relative expression of Bv8 among the subjects was compared via quantitative PCR analysis. Utilizing this approach no significant difference was detected in the mean LogRQ values between the first and second blood draws (t-test, p = 0.826) indicating low intra-patient variability and demonstrating good reproducibility of the assay. There was no significant difference in Bv8 expression between nvAMD subjects classified as refractory versus non-refractory. We were unable to find a correlation between Bv8 expression in CD11b + cells and anti-VEGF refractoriness in human nvAMD subjects. Relatively high expression in Bv8 in these subjects did not correlate with clinical treatment history, as measured by the frequency of injections. Utilizing this well characterized technique, studies are underway to examine alternative gene expression profiles in various circulating cell populations that may contribute to anti-VEGF refractoriness.

  13. Endocrine vasculatures are preferable targets of an antitumor ineffective low dose of anti-VEGF therapy

    PubMed Central

    Zhang, Yin; Yang, Yunlong; Hosaka, Kayoko; Huang, Guichun; Zang, Jingwu; Chen, Fang; Zhang, Yun; Samani, Nilesh J.; Cao, Yihai

    2016-01-01

    Anti-VEGF–based antiangiogenic drugs are designed to block tumor angiogenesis for treatment of cancer patients. However, anti-VEGF drugs produce off-tumor target effects on multiple tissues and organs and cause broad adverse effects. Here, we show that vasculatures in endocrine organs were more sensitive to anti-VEGF treatment than tumor vasculatures. In thyroid, adrenal glands, and pancreatic islets, systemic treatment with low doses of an anti-VEGF neutralizing antibody caused marked vascular regression, whereas tumor vessels remained unaffected. Additionally, a low dose of VEGF blockade significantly inhibited the formation of thyroid vascular fenestrae, leaving tumor vascular structures unchanged. Along with vascular structural changes, the low dose of VEGF blockade inhibited vascular perfusion and permeability in thyroid, but not in tumors. Prolonged treatment with the low-dose VEGF blockade caused hypertension and significantly decreased circulating levels of thyroid hormone free-T3 and -T4, leading to functional impairment of thyroid. These findings show that the fenestrated microvasculatures in endocrine organs are more sensitive than tumor vasculatures in response to systemic anti-VEGF drugs. Thus, our data support the notion that clinically nonbeneficial treatments with anti-VEGF drugs could potentially cause adverse effects. PMID:27035988

  14. Macular ischaemia: a contraindication for anti-VEGF treatment in retinal vascular disease?

    PubMed

    Manousaridis, Kleanthis; Talks, James

    2012-02-01

    Anti-vascular endothelial growth factor (anti-VEGF) therapy has been shown to be effective at improving vision in patients with macular oedema due to diabetic retinopathy and vein occlusions, but blocking VEGF at least in theory could be detrimental to vascular integrity. For this reason, some patients with macular ischaemia were excluded from studies showing the effectiveness of therapy. A considerable number of patients present with mixed pathology of macular oedema and macular ischaemia and it is often impossible to determine the degree to which ischaemia accounts for decreased vision. In this review, the authors have dealt with the specific question of whether or not there is evidence to support potential worsening of the macular perfusion and visual function after anti-VEGF treatment with bevacizumab or ranibizumab for macular oedema secondary to diabetic retinopathy or retinal vein occlusions, especially if there is coexisting macular ischaemia. The authors conclude that anti-VEGF therapy rarely seems to further compromise the retinal circulation; however, worsening of macular ischaemia in the long term cannot be definitely excluded, particularly in eyes with significant ischaemia at baseline and after repeated intraocular anti-VEGF injections. The decision to offer prolonged anti-VEGF treatment in cases of significant coexisting macular ischaemia should not be based only on measurements of macular thickness; instead repeat fluorescein angiograms should be performed.

  15. Influence of anti-VEGF about cardiovascular biomarkers in age related macular degeneration.

    PubMed

    Manresa, N; Mulero, J; Losada, M; Zafrilla, P

    2015-02-01

    Systemic VEGF inhibition disrupts endothelial homeostasis and accelerates the atherogenesis, suggesting that these events contribute to the clinical cardiovascular adverse events of VEGF-inhibiting therapies. The objective of the current study was to analyze the effect of anti-VEGF therapy on cardiovascular risk factors in patients with exudative age related macular degeneration. A total of 73 patients with exudative age related macular degeneration (without previous anti-VEGF therapy) were treated with two anti-VEGF: Ranibizumab and Pegaptanib sodium. The follow up was 6 months. The following parameters were determined before and after treatment: homocysteine, lipids (total cholesterol, triglycerides, HDL-c, LDL-c), C-Reactive Protein and fibrinogen. There were not statistically significant differences in parameters studied before and after treatment with both Pegaptanib sodium and Ranibizumab, except C-Reactive Protein. Of all patients analyzed, only 3 of them have initially C-Reactive Protein levels above normal levels and after antiangiogenic therapy, there was a significant increase in C-Reactive Protein. We have not found results in our study who to suspect that treatment with anti-VEGF in the patients with exudative age related macular degeneration increases cardiovascular risk predictors. However, after therapy was increased the CRP and fibrinogen may mean that anti-VEGF contribute an alteration of endothelial homeostasis in exudative AMD.

  16. Association of Anti-VEGF Injections with Progression of Geographic Atrophy.

    PubMed

    Enslow, Ryan; Bhuvanagiri, Sai; Vegunta, Sravanthi; Cutler, Benjamin; Neff, Michael; Stagg, Brian

    2016-01-01

    Age-related macular degeneration (AMD) is one of the leading causes of blindness in developed countries in people over the age of 60 years. One of the forms of advanced AMD is wet AMD. Wet AMD is a result of leakage and bleeding from abnormal neovascularization. The principal treatment for wet AMD is intravitreal anti-VEGF injections. A second form of advanced AMD is geographic atrophy (GA). GA refers to large areas of retinal pigment epithelium loss. In the literature, there is some concern that anti-VEGF injections administered to treat wet AMD may be associated with progression of GA. This review discusses evidence suggesting the association of anti-VEGF injections with progression of GA.

  17. The Application of OCTA in Assessment of Anti-VEGF Therapy for Idiopathic Choroidal Neovascularization

    PubMed Central

    Sun, Zihan; Dai, Hong

    2016-01-01

    Purpose. To assess the morphology of idiopathic choroidal neovascularization (ICNV) by optical coherence tomography angiography (OCTA) and determine the therapeutic effects of intravitreal antivascular endothelial growth factor (anti-VEGF). Method. Patients with naive ICNV were assessed by spectral domain optical coherence tomography (SD-OCT) and OCTA in this observational study. The timing of observation was before treatment, 1 day after treatment with intravitreal anti-VEGF injection, and 1 month after the treatment. The central retina thickness (CRT) on SD-OCT, selected CNV area, and flow area on OCTA were measured. Results. A total of 17 eyes from 17 patients with ICNV were included in this study. OCTA showed visible irregular choroidal neovascularization with “tree-in-bud” form on outer retinal layer. After treatment, as well as in the 1-day follow-up, CNV decreased in size from the periphery, and the vessel density was reduced. As shown on OCTA, the selected CNV area and flow area were significantly reduced compared to pretreatment. The rate of CNV vessel area changes was higher on OCTA than the changes in CRT on SD-OCT at 1-day and 1-month follow-up. Conclusion. Intravitreal injection of anti-VEGF is effective for idiopathic choroidal neovascularization, and the treatment outcomes are observable after 1 day. OCTA provides a useful approach for monitoring and evaluating the treatment of intravitreal anti-VEGF for CNV. PMID:27471600

  18. Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: a comprehensive review.

    PubMed

    Yang, Shiqi; Zhao, Jingke; Sun, Xiaodong

    2016-01-01

    As a progressive chronic disease, age-related macular degeneration (AMD) is the leading cause of irreversible vision impairment worldwide. Experimental and clinical evidence has demonstrated that vascular endothelial growth factor (VEGF) plays a vital role in the formation of choroidal neovascularization. Intravitreal injections of anti-VEGF agents have been recommended as a first-line treatment for neovascular AMD. However, persistent fluid or recurrent exudation still occurs despite standardized anti-VEGF therapy. Patients suffering from refractory or recurrent neovascular AMD may develop mechanisms of resistance to anti-VEGF therapy, which results in a diminished therapeutic effect. Until now, there has been no consensus on the definitions of refractory neovascular AMD and recurrent neovascular AMD. This article aims at clarifying these concepts to evaluate the efficacy of switching drugs, which contributes to making clinical decision more scientifically. Furthermore, insight into the causes of resistance to anti-VEGF therapy would be helpful for developing possible therapeutic approaches, such as combination therapy and multi-target treatment that can overcome this resistance.

  19. Resistance to anti-VEGF therapy in neovascular age-related macular degeneration: a comprehensive review

    PubMed Central

    Yang, Shiqi; Zhao, Jingke; Sun, Xiaodong

    2016-01-01

    As a progressive chronic disease, age-related macular degeneration (AMD) is the leading cause of irreversible vision impairment worldwide. Experimental and clinical evidence has demonstrated that vascular endothelial growth factor (VEGF) plays a vital role in the formation of choroidal neovascularization. Intravitreal injections of anti-VEGF agents have been recommended as a first-line treatment for neovascular AMD. However, persistent fluid or recurrent exudation still occurs despite standardized anti-VEGF therapy. Patients suffering from refractory or recurrent neovascular AMD may develop mechanisms of resistance to anti-VEGF therapy, which results in a diminished therapeutic effect. Until now, there has been no consensus on the definitions of refractory neovascular AMD and recurrent neovascular AMD. This article aims at clarifying these concepts to evaluate the efficacy of switching drugs, which contributes to making clinical decision more scientifically. Furthermore, insight into the causes of resistance to anti-VEGF therapy would be helpful for developing possible therapeutic approaches, such as combination therapy and multi-target treatment that can overcome this resistance. PMID:27330279

  20. Intravitreal Anti-VEGF Injections in Pregnancy: Case Series and Review of Literature.

    PubMed

    Polizzi, Silvio; Mahajan, Vinit B

    2015-12-01

    The use of intravitreal antivascular endothelial growth factor (anti-VEGF) injection is gaining wide acceptance as an off-label therapy for diseases that may affect pregnant women. However, these drugs may cause systemic side effects in the mother and fetal harm. This could lead specialists to not administer the drug or women to abort the fetus or to refuse treatment during pregnancy. We report the course of pregnancy in 3 women treated with intravitreal bevacizumab and provide a review of the literature on the use of intravitreal anti-VEGF in pregnancy. Our patients did not have any drug-related adverse event and delivered healthy full-term infants, although one of the women had risk factors for miscarriage. Infants reached all developmental milestones appropriately during infancy. A literature search on the use of intravitreal anti-VEGF injection in pregnancy was undertaken. Data for this review were identified by searches of PubMed and references from relevant articles using the search terms "pegaptanib," "bevacizumab," "ranibizumab," "aflibercept," "anti-VEGF," "intravitreal injection," "pregnant," "pregnancy," "abortion," "miscarriage," "preeclampsia," "embryo-fetal toxicity," "fetal malformations," "teratogenesis," "adverse events," and "maternofetal complications" in multiple combinations. We believe that intravitreal anti-VEGF can be given during pregnancy only when potential benefit to the woman justifies the potential risks to the fetus. When making a decision about whether to give drugs during pregnancy, it is important to consider the timing of exposure and its relationship to windows of developmental sensitivity. We believe that this review will be useful to specialists to inform and possibly treat their pregnant patients.

  1. Intravitreal Anti-VEGF Injections in Pregnancy: Case Series and Review of Literature

    PubMed Central

    Mahajan, Vinit B.

    2015-01-01

    Abstract The use of intravitreal antivascular endothelial growth factor (anti-VEGF) injection is gaining wide acceptance as an off-label therapy for diseases that may affect pregnant women. However, these drugs may cause systemic side effects in the mother and fetal harm. This could lead specialists to not administer the drug or women to abort the fetus or to refuse treatment during pregnancy. We report the course of pregnancy in 3 women treated with intravitreal bevacizumab and provide a review of the literature on the use of intravitreal anti-VEGF in pregnancy. Our patients did not have any drug-related adverse event and delivered healthy full-term infants, although one of the women had risk factors for miscarriage. Infants reached all developmental milestones appropriately during infancy. A literature search on the use of intravitreal anti-VEGF injection in pregnancy was undertaken. Data for this review were identified by searches of PubMed and references from relevant articles using the search terms “pegaptanib,” “bevacizumab,” “ranibizumab,” “aflibercept,” “anti-VEGF,” “intravitreal injection,” “pregnant,” “pregnancy,” “abortion,” “miscarriage,” “preeclampsia,” “embryo–fetal toxicity,” “fetal malformations,” “teratogenesis,” “adverse events,” and “maternofetal complications” in multiple combinations. We believe that intravitreal anti-VEGF can be given during pregnancy only when potential benefit to the woman justifies the potential risks to the fetus. When making a decision about whether to give drugs during pregnancy, it is important to consider the timing of exposure and its relationship to windows of developmental sensitivity. We believe that this review will be useful to specialists to inform and possibly treat their pregnant patients. PMID:26302032

  2. Diffusion of anti-VEGF injections in the Portuguese National Health System

    PubMed Central

    Marques, Ana Patrícia; Macedo, António Filipe; Perelman, Julian; Aguiar, Pedro; Rocha-Sousa, Amândio; Santana, Rui

    2015-01-01

    Objectives To analyse the temporal and geographical diffusion of antivascular endothelial growth factor (anti-VEGF) interventions, and its determinants in a National Health System (NHS). Setting NHS Portuguese hospitals. Participants All inpatient and day cases related to eye diseases at all Portuguese public hospitals for the period 2002–2012 were selected on the basis of four International Classification of Diseases 9th revision, Clinical Modification (ICD-9-CM) codes for procedures: 1474, 1475, 1479 and 149. Primary and secondary outcome measures We measured anti-VEGF treatment rates by year and county. The determinants of the geographical diffusion were investigated using generalised linear modelling. Results We analysed all hospital discharges from all NHS hospitals in Portugal (98 408 hospital discharges corresponding to 57 984 patients). National rates of hospitals episodes for the codes for procedures used were low before anti-VEGF approval in 2007 (less than 12% of hospital discharges). Between 2007 and 2012, the rates of hospital episodes related to the introduction of anti-VEGF injections increased by 27% per year. Patients from areas without ophthalmology departments received fewer treatments than those from areas with ophthalmology departments. The availability of an ophthalmology department in the county increased the rates of hospital episodes by 243%, and a 100-persons greater density per km2 raised the rates by 11%. Conclusions Our study shows a large but unequal diffusion of anti-VEGF treatments despite the universal coverage and very low copayments. The technological innovation in ophthalmology may thus produce unexpected inequalities related to financial constraints unless the implementation of innovative techniques is planned and regulated. PMID:26597866

  3. Comparison of the efficacy of anti-VEGF monotherapy versus PDT and intravitreal anti-VEGF combination treatment in AMD: a Meta-analysis and systematic review

    PubMed Central

    Tong, Yao; Zhao, Ke-Ke; Feng, Dong; Biswal, Manas; Zhao, Pei-Quan; Wang, Zhao-Yang; Zhang, Yun

    2016-01-01

    AIM To compare the effect of anti-vascular endothelial growth factor (VEGF) monotherapy versus photodynamic therapy (PDT) and anti-VEGF combination treatment in age-related macular degeneration (AMD). METHODS A computerized online search was performed using PubMed, Web of Science and the Cochrane Library. Studies that compared anti-VEGF monotherapy with PDT and anti-VEGF combination treatment of AMD and were designed as randomized controlled trials were included. The means and standard deviations of the best-corrected visual acuity (BCVA), central retinal thickness (CRT), number of treatments and proportions of patients who gained BCVA ≥15, 10, 5, or 0 letters at 12th month were extracted. A systematic review and Meta-analysis of the comparison of the two approaches was conducted using Review Manager 5.2. Subgroup. A sensitivity analysis was also performed. RESULTS Eight studies were included. When the subgroup and sensitivity analysis was conducted, the results indicated that in the findings that included the monotherapy group and PDT (standard fluence, SF) group of Kaiser's study, the patients in the monotherapy group had a better BCVA compared with the combination group at 12th month in the PDT (SF) subgroup [weighted mean difference (WMD): 3.54; 95%CI: 0.36 to 6.73; P=0.03], and there were more patients who gained ≥15 letters of BCVA in the monotherapy group compared with the combination group in the total result [odds ratio (OR): 1.41; 95%CI: 1.02 to 1.95; P=0.04]. The same conclusion was obtained in the total result that included the monotherapy group and PDT (reduced fluence, RF) group of Kaiser's study (OR: 1.56; 95%CI: 1.13 to 2.15; P=0.007). However, there were no significant differences in the other indexes between the two therapies. CONCLUSION We found that anti-VEGF monotherapy is more effective on the recovery of visual acuity than combination therapy and more researches with lager sample size should be performed to study on the effect of the two

  4. Risk of geographic atrophy in age-related macular degeneration patients treated with intravitreal anti-VEGF agents.

    PubMed

    Gemenetzi, M; Lotery, A J; Patel, P J

    2017-01-01

    Anti-vascular endothelial growth factor (VEGF) intravitreal agents are the only successful treatment for wet age-related macular degeneration (AMD). However, there are emerging signals that anti-VEGF treatment can potentially increase development of geographic atrophy (GA). Histopathologic, animal, and clinical studies support this hypothesis although direct proof of a relationship between GA and use of anti-VEGF agents in neovascular AMD is not yet established. This review presents current evidence supporting an association between anti-VEGF therapy and progression of geographic atrophy. The need of exploring alternative methods of treating AMD is indirectly but clearly emphasized.

  5. Management of Myopic Choroidal Neovascularization: Focus on Anti-VEGF Therapy.

    PubMed

    Teo, Kelvin Yi Chong; Ng, Wei Yan; Lee, Shu Yen; Cheung, Chui Ming Gemmy

    2016-07-01

    Myopic choroidal neovascularization (mCNV) is the second most common form of CNV after age-related macular degeneration (AMD). It is a sight-threatening complication of pathologic myopia (PM) and often affects patients in their working years causing significant impact on quality of life. Previous therapies such as photodynamic therapy with verteporfin have shown limited success. Due to the similarities in pathogenesis of mCNV and AMD CNV, anti-vascular endothelial growth factor therapy (anti-VEGF), which has so far been the mainstay of treatment for AMD CNV, has been shown to be effective in the treatment of mCNV and has become the first-line treatment of choice. This article aims to examine briefly the epidemiology and pathophysiology of mCNV, as well as review the evidence for efficacy, safety, and clinical use of anti-VEGF treatment for mCNV.

  6. Retinal reperfusion in diabetic retinopathy following treatment with anti-VEGF intravitreal injections

    PubMed Central

    Levin, Ariana M; Rusu, Irene; Orlin, Anton; Gupta, Mrinali P; Coombs, Peter; D’Amico, Donald J; Kiss, Szilárd

    2017-01-01

    Purpose The aim of this study is to report peripheral reperfusion of ischemic areas of the retina on ultra-widefield fluorescein angiography (UWFA) following anti-vascular endothelial growth factor (VEGF) intravitreal injections in patients treated for diabetic retinopathy. Methods This study is a retrospective review of 16 eyes of 15 patients with diabetic retinopathy, who received anti-VEGF intravitreal injections and underwent pre- and postinjection UWFA. The main outcome measured was the presence of reperfusion in postinjection UWFA images in areas of the retina that demonstrated nonperfusion in preinjection images. Images were analyzed for reperfusion qualitatively and quantitatively by two graders. Results Twelve of 16 eyes (75%) or 11 of 15 patients (73.3%) demonstrated reperfusion following anti-VEGF injection. On UWFA, reperfusion was detected both within the field of 7-standard field (7SF) fluorescein angiography and in the periphery outside the 7SF. Four of 16 eyes or 4 of 15 patients did not demonstrate reperfusion, one of which had extensive scarring from prior panretinal photocoagulation. Conclusion In patients with diabetic retinopathy, treatment with anti-VEGF agents can be associated with reperfusion of areas of nonperfusion, as demonstrated by UWFA. PMID:28176934

  7. The Role of Anti-VEGF Therapy in the Treatment of Diabetic Macular Edema.

    PubMed

    Moshfeghi, Darius M; Kaiser, Peter K; Michels, Stephan; Midena, Edoardo; Kitchens, John W; Prenner, Jonathan L; Regillo, Carl D; Reichel, Elias

    2016-06-01

    Diabetic retinopathy (DR) is the leading cause of blindness among working-age adults. DR often leads to diabetic macular edema (DME), which often goes unnoticed until a patient presents with vision loss. However, treatment options and data for DME are continually improving. We know that vascular endothelial growth factor (VEGF) plays a key role in DME progression; therapies that act by inhibiting VEGF production seem to improve visual acuity in patients with DME. Of the anti-VEGF therapies available, two have been approved by the U.S. Food and Drug Administration to treat DME: ranibizumab (Lucentis; Genentech, South San Francisco, CA) and aflibercept (Eylea; Regeneron, Tarrytown, NY). Bevacizumab (Avastin; Genentech, South San Francisco, CA), which is approved for the treatment of certain types of cancer, is occasionally used off-label to treat DME. Anti-VEGF therapy can stop vision loss and even improve visual acuity. Other treatments remain effective, and these various treatment options fuel a need for new data and discussion. This roundtable discussion, which took place during the 2015 annual meeting of the American Academy of Ophthalmology, outlines the current protocols used to treat DME and provides clinical opinions about selecting and treating with an appropriate anti-VEGF therapy. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:S5-14.].

  8. Anti-VEGF therapy induces ECM remodeling and mechanical barriers to therapy in colorectal cancer liver metastases.

    PubMed

    Rahbari, Nuh N; Kedrin, Dmitriy; Incio, Joao; Liu, Hao; Ho, William W; Nia, Hadi T; Edrich, Christina M; Jung, Keehoon; Daubriac, Julien; Chen, Ivy; Heishi, Takahiro; Martin, John D; Huang, Yuhui; Maimon, Nir; Reissfelder, Christoph; Weitz, Jurgen; Boucher, Yves; Clark, Jeffrey W; Grodzinsky, Alan J; Duda, Dan G; Jain, Rakesh K; Fukumura, Dai

    2016-10-12

    The survival benefit of anti-vascular endothelial growth factor (VEGF) therapy in metastatic colorectal cancer (mCRC) patients is limited to a few months because of acquired resistance. We show that anti-VEGF therapy induced remodeling of the extracellular matrix with subsequent alteration of the physical properties of colorectal liver metastases. Preoperative treatment with bevacizumab in patients with colorectal liver metastases increased hyaluronic acid (HA) deposition within the tumors. Moreover, in two syngeneic mouse models of CRC metastasis in the liver, we show that anti-VEGF therapy markedly increased the expression of HA and sulfated glycosaminoglycans (sGAGs), without significantly changing collagen deposition. The density of these matrix components correlated with increased tumor stiffness after anti-VEGF therapy. Treatment-induced tumor hypoxia appeared to be the driving force for the remodeling of the extracellular matrix. In preclinical models, we show that enzymatic depletion of HA partially rescued the compromised perfusion in liver mCRCs after anti-VEGF therapy and prolonged survival in combination with anti-VEGF therapy and chemotherapy. These findings suggest that extracellular matrix components such as HA could be a potential therapeutic target for reducing physical barriers to systemic treatments in patients with mCRC who receive anti-VEGF therapy.

  9. Genetic predictive biomarkers of anti-VEGF treatment response in patients with neovascular age-related macular degeneration.

    PubMed

    Fauser, Sascha; Lambrou, George N

    2015-01-01

    Anti-vascular endothelial growth factor (anti-VEGF) therapies for neovascular age-related macular degeneration (nAMD) have proven efficacy at a study-population level, although individual patient responses vary, with most of the patients responding well to anti-VEGF therapies, while a few respond poorly. The pathogenesis of AMD is known to have a genetic component, but it is unclear if any particular genotype can predict response to anti-VEGF therapy. With the advent of less expensive genotyping technology, there have been numerous studies within this area. Here we analyze potential biomarker candidates identified that could be used in a clinical setting to predict response to anti-VEGF treatment of nAMD. We analyze single nucleotide polymorphisms (SNPs) identified from 39 publications. The SNPs that appeared to be of most importance fell into two main groups: those previously associated with AMD pathogenesis and those within the signaling pathway targeted by anti-VEGF therapies. A number of small studies found evidence supporting an association between anti-VEGF treatment response and two SNPs, CFH rs1061170 and VEGFA rs699947, but results from randomized controlled trials found no such association. It is possible that, in the future, the cumulative effect of several high-risk SNPs may prove useful in a clinical setting and that other genetic biomarkers may emerge.

  10. Switch to Aflibercept in Diabetic Macular Edema Patients Unresponsive to Previous Anti-VEGF Therapy

    PubMed Central

    Paulo, Manuel; Henriques, Filipe; Figueira, João

    2017-01-01

    Purpose. The aim was to evaluate the efficacy of aflibercept in patients with diabetic macular edema (DME) unresponsive to prior anti-VEGF therapy. Methods. Retrospective review of DME unresponsive to previous anti-VEGF switched to aflibercept with 3 months of follow-up. Changes in best correct visual acuity (BCVA), central retinal thickness (CRT), and frequency of injections were analyzed. The percentage of subjects who had ≥20/40 (logMAR equivalent 0.3) and ≤20/200 (logMAR equivalent 1) was evaluated. Results. A total of 32 eyes from 26 patients were included. Mean age was 65 ± 10 years old. The mean number of previous anti-VEGF injections was 5.34 ± 2.38, and the mean number of aflibercept injections at the end of the study was 2.00 ± 0.00. The CRT at baseline was 501.47 ± 150.51 μm and 367.97 ± 124.61 μm at 3 months of follow-up (P < 0.001). The logMAR BCVA at baseline was 0.71 ± 0.36 and 0.65 ± 0.33 at the end of the follow-up (P = 0.037). At baseline, 12.5% of patients had ≥20/40 compared with 25% at the end of follow-up. At baseline, 28.13% of patients had 20/200 or inferior vision compared with 15.63% at the end of the follow-up. Conclusions. DME patients unresponsive to previous multiple ranibizumab injections demonstrate a significant anatomical and functional improvement with the switch to aflibercept. PMID:28348885

  11. A novel small molecule ameliorates ocular neovascularisation and synergises with anti-VEGF therapy

    PubMed Central

    Sulaiman, Rania S.; Merrigan, Stephanie; Quigley, Judith; Qi, Xiaoping; Lee, Bit; Boulton, Michael E.; Kennedy, Breandán; Seo, Seung-Yong; Corson, Timothy W.

    2016-01-01

    Ocular neovascularisation underlies blinding eye diseases such as retinopathy of prematurity, proliferative diabetic retinopathy, and wet age-related macular degeneration. These diseases cause irreversible vision loss, and provide a significant health and economic burden. Biologics targeting vascular endothelial growth factor (VEGF) are the major approach for treatment. However, up to 30% of patients are non-responsive to these drugs and they are associated with ocular and systemic side effects. Therefore, there is a need for small molecule ocular angiogenesis inhibitors to complement existing therapies. We examined the safety and therapeutic potential of SH-11037, a synthetic derivative of the antiangiogenic homoisoflavonoid cremastranone, in models of ocular neovascularisation. SH-11037 dose-dependently suppressed angiogenesis in the choroidal sprouting assay ex vivo and inhibited ocular developmental angiogenesis in zebrafish larvae. Additionally, intravitreal SH-11037 (1 μM) significantly reduced choroidal neovascularisation (CNV) lesion volume in the laser-induced CNV mouse model, comparable to an anti-VEGF antibody. Moreover, SH-11037 synergised with anti-VEGF treatments in vitro and in vivo. Up to 100 μM SH-11037 was not associated with signs of ocular toxicity and did not interfere with retinal function or pre-existing retinal vasculature. SH-11037 is thus a safe and effective treatment for murine ocular neovascularisation, worthy of further mechanistic and pharmacokinetic evaluation. PMID:27148944

  12. Coaxial Electrospray of Ranibizumab-Loaded Microparticles for Sustained Release of Anti-VEGF Therapies

    PubMed Central

    Fischer, Andrew J.; Letson, Alan; Yuan, Shuai; Roberts, Cynthia J.; Xu, Ronald X.

    2015-01-01

    Age-related macular degeneration (AMD) is the leading cause of vision loss and blindness in people over age 65 in industrialized nations. Intravitreous injection of anti-VEGF (vascular endothelial growth factor) therapies, such as ranibizumab (trade name: Lucentis), provides an effective treatment option for neovascular AMD. We have developed an improved coaxial electrospray (CES) process to encapsulate ranibizumab in poly(lactic-co-glycolic) acid (PLGA) microparticles (MPs) for intravitreous injection and sustained drug release. This microencapsulation process is advantageous for maintaining the stability of the coaxial cone-jet configurations and producing drug-loaded MPs with as high as 70% encapsulation rate and minimal loss of bioactivitiy. The utility of this emerging process in intravitreous drug delivery has been demonstrated in both benchtop and in vivo experiments. The benchtop test simulates ocular drug release using PLGA MPs encapsulating a model drug. The in vivo experiment evaluates the inflammation and retinal cell death after intravitreal injection of the MPs in a chick model. The experimental results show that the drug-load MPs are able to facilitate sustained drug release for longer than one month. No significant long term microglia reaction or cell death is observed after intravitreal injection of 200 μg MPs. The present study demonstrates the technical feasibility of using the improved CES process to encapsulate water-soluble drugs at a high concentration for sustained release of anti-VEGF therapy. PMID:26273831

  13. Effects of Anti-VEGF on Predicted Antibody Biodistribution: Roles of Vascular Volume, Interstitial Volume, and Blood Flow

    PubMed Central

    Boswell, C. Andrew; Ferl, Gregory Z.; Mundo, Eduardo E.; Bumbaca, Daniela; Schweiger, Michelle G.; Theil, Frank-Peter; Fielder, Paul J.; Khawli, Leslie A.

    2011-01-01

    Background The identification of clinically meaningful and predictive models of disposition kinetics for cancer therapeutics is an ongoing pursuit in drug development. In particular, the growing interest in preclinical evaluation of anti-angiogenic agents alone or in combination with other drugs requires a complete understanding of the associated physiological consequences. Methodology/Principal Findings Technescan™ PYP™, a clinically utilized radiopharmaceutical, was used to measure tissue vascular volumes in beige nude mice that were naïve or administered a single intravenous bolus dose of a murine anti-vascular endothelial growth factor (anti-VEGF) antibody (10 mg/kg) 24 h prior to assay. Anti-VEGF had no significant effect (p>0.05) on the fractional vascular volumes of any tissues studied; these findings were further supported by single photon emission computed tomographic imaging. In addition, apart from a borderline significant increase (p = 0.048) in mean hepatic blood flow, no significant anti-VEGF-induced differences were observed (p>0.05) in two additional physiological parameters, interstitial fluid volume and the organ blood flow rate, measured using indium-111-pentetate and rubidium-86 chloride, respectively. Areas under the concentration-time curves generated by a physiologically-based pharmacokinetic model changed substantially (>25%) in several tissues when model parameters describing compartmental volumes and blood flow rates were switched from literature to our experimentally derived values. However, negligible changes in predicted tissue exposure were observed when comparing simulations based on parameters measured in naïve versus anti-VEGF-administered mice. Conclusions/Significance These observations may foster an enhanced understanding of anti-VEGF effects in murine tissues and, in particular, may be useful in modeling antibody uptake alone or in combination with anti-VEGF. PMID:21436893

  14. Lack of anti-tumor activity by anti-VEGF treatments in hepatic hemangiomas.

    PubMed

    Lee, Minsu; Choi, Jin-Young; Lim, Joon Seok; Park, Mi-Suk; Kim, Myeong-Jin; Kim, Honsoul

    2016-04-01

    Recently, anti-vascular endothelial growth factor (anti-VEGF) agents have been described in the literature as a valid treatment option for symptomatic liver hemangiomas, but only limited evidence supports this notion. The purpose of this study was to elucidate whether or not the administration of anti-VEGF agents can reliably achieve a size reduction in liver hemangiomas. We examined patients with incidental hemangiomas who received anti-angiogenic agents for the treatment of other malignancies. Our study population consisted of 17 colorectal cancer patients and one lung cancer patient carrying 21 hemangiomas who received bevacizumab, and seven renal cell carcinoma patients carrying nine hepatic hemangiomas who received sunitinib. We have measured the liver hemangioma volume on both the pre-treatment and post-treatment computed tomography images and then calculated the volume alteration rates. No statistically significant difference (P = 0.365) in the volume of the liver hemangiomas was observed before (1.1-168.8 cm(3); mean ± SD 19.8 ± 39.7 cm(3)) or after (1.2-163.6 cm(3); 19.3 ± 38.0 cm(3)) bevacizumab treatment. The volume reduction rate ranged from -35.0 to 11.2 % (mean ± SD -1.3 ± 10.8 %). The sunitinib treatment group also showed no statistically significant difference (P = 0.889) in hemangioma volume before (1.2-6.5 cm(3); 3.0 ± 1.8 cm(3)) or after (1.2-6.0 cm(3); 3.0-1.7 cm(3)) treatment. The volume reduction rate ranged from -13.3 to 7.7 % (median: mean ± SD -2.5 ± 6.6 %). We did not observe liver hemangioma shrinkage after bevacizumab or sunitinib treatment. Our data do not support the application of anti-VEGF agents for the treatment of hepatic hemangiomas.

  15. Purification of rabbit and human serum paraoxonase.

    PubMed

    Furlong, C E; Richter, R J; Chapline, C; Crabb, J W

    1991-10-22

    Rabbit serum paraoxonase/arylesterase has been purified to homogeneity by Cibacron Blue-agarose chromatography, gel filtration, DEAE-Trisacryl M chromatography, and preparative SDS gel electrophoresis. Renaturation (Copeland et al., 1982) and activity staining of the enzyme resolved by SDS gel electrophoresis allowed for identification and purification of paraoxonase. Two bands of active enzyme were purified by this procedure (35,000 and 38,000). Enzyme electroeluted from the preparative gels was reanalyzed by analytical SDS gel electrophoresis, and two higher molecular weight bands (43,000 and 48,000) were observed in addition to the original bands. This suggested that repeat electrophoresis resulted in an unfolding or other modification and slower migration of some of the purified protein. The lower mobility bands stained weakly for paraoxonase activity in preparative gels. Bands of each molecular weight species were electroblotted onto PVDF membranes and sequenced. The gas-phase sequence analysis showed that both the active bands and apparent molecular weight bands had identical amino-terminal sequences. Amino acid analysis of the four electrophoretic components from PVDF membranes also indicated compositional similarity. The amino-terminal sequences are typical of the leader sequences of secreted proteins. Human serum paraoxonase was purified by a similar procedure, and ten residues of the amino terminus were sequenced by gas-phase procedures. One amino acid difference between the first ten residues of human and rabbit was observed.

  16. Targeting activin receptor-like kinase 1 inhibits angiogenesis and tumorigenesis through a mechanism of action complementary to anti-VEGF therapies.

    PubMed

    Hu-Lowe, Dana D; Chen, Enhong; Zhang, Lianglin; Watson, Katherine D; Mancuso, Patrizia; Lappin, Patrick; Wickman, Grant; Chen, Jeffrey H; Wang, Jianying; Jiang, Xin; Amundson, Karin; Simon, Ronald; Erbersdobler, Andreas; Bergqvist, Simon; Feng, Zheng; Swanson, Terri A; Simmons, Brett H; Lippincott, John; Casperson, Gerald F; Levin, Wendy J; Stampino, Corrado Gallo; Shalinsky, David R; Ferrara, Katherine W; Fiedler, Walter; Bertolini, Francesco

    2011-02-15

    Genetic and molecular studies suggest that activin receptor-like kinase 1 (ALK1) plays an important role in vascular development, remodeling, and pathologic angiogenesis. Here we investigated the role of ALK1 in angiogenesis in the context of common proangiogenic factors [PAF; VEGF-A and basic fibroblast growth factor (bFGF)]. We observed that PAFs stimulated ALK1-mediated signaling, including Smad1/5/8 phosphorylation, nuclear translocation and Id-1 expression, cell spreading, and tubulogenesis of endothelial cells (EC). An antibody specifically targeting ALK1 (anti-ALK1) markedly inhibited these events. In mice, anti-ALK1 suppressed Matrigel angiogenesis stimulated by PAFs and inhibited xenograft tumor growth by attenuating both blood and lymphatic vessel angiogenesis. In a human melanoma model with acquired resistance to a VEGF receptor kinase inhibitor, anti-ALK1 also delayed tumor growth and disturbed vascular normalization associated with VEGF receptor inhibition. In a human/mouse chimera tumor model, targeting human ALK1 decreased human vessel density and improved antitumor efficacy when combined with bevacizumab (anti-VEGF). Antiangiogenesis and antitumor efficacy were associated with disrupted co-localization of ECs with desmin(+) perivascular cells, and reduction of blood flow primarily in large/mature vessels as assessed by contrast-enhanced ultrasonography. Thus, ALK1 may play a role in stabilizing angiogenic vessels and contribute to resistance to anti-VEGF therapies. Given our observation of its expression in the vasculature of many human tumor types and in circulating ECs from patients with advanced cancers, ALK1 blockade may represent an effective therapeutic opportunity complementary to the current antiangiogenic modalities in the clinic.

  17. The Structural Basis for the Function of Two Anti-VEGF Receptor 2 Antibodies

    SciTech Connect

    M Franklin; E Navarro; Y Wang; S Patel; P Singh; Y Zhang; K Persaud; A Bari; H Griffith; et al.

    2011-12-31

    The anti-VEGF receptor 2 antibody IMC-1121B is a promising antiangiogenic drug being tested for treatment of breast and gastric cancer. We have determined the structure of the 1121B Fab fragment in complex with domain 3 of VEGFR2, as well as the structure of a different neutralizing anti-VEGFR2 antibody, 6.64, also in complex with VEGFR2 domain 3. The two Fab fragments bind at opposite ends of VEGFR2 domain 3; 1121B directly blocks VEGF binding, whereas 6.64 may prevent receptor dimerization by perturbing the domain 3:domain 4 interface. Mutagenesis reveals that residues essential for VEGF, 1121B, and 6.64 binding are nonoverlapping among the three contact patches.

  18. The Structural Basis for the Function of Two Anti-VEGF Receptor 2 Antibodies

    SciTech Connect

    Franklin, Matthew C.; Navarro, Elizabeth C.; Wang, Yujie; Patel, Sheetal; Singh, Pinki; Zhang, Yi; Persaud, Kris; Bari, Amtul; Griffith, Heather; Shen, Leyi; Balderes, Paul; Kussie, Paul

    2011-10-28

    The anti-VEGF receptor 2 antibody IMC-1121B is a promising antiangiogenic drug being tested for treatment of breast and gastric cancer. We have determined the structure of the 1121B Fab fragment in complex with domain 3 of VEGFR2, as well as the structure of a different neutralizing anti-VEGFR2 antibody, 6.64, also in complex with VEGFR2 domain 3. The two Fab fragments bind at opposite ends of VEGFR2 domain 3; 1121B directly blocks VEGF binding, whereas 6.64 may prevent receptor dimerization by perturbing the domain 3:domain 4 interface. Mutagenesis reveals that residues essential for VEGF, 1121B, and 6.64 binding are nonoverlapping among the three contact patches.

  19. Combination of Anti-VEGF and Laser Photocoagulation for Diabetic Macular Edema: A Review

    PubMed Central

    Garcia-Arumi, Jose; Boixadera, Anna

    2017-01-01

    Diabetic macular edema (DME) is the most common cause of vision loss in diabetic patients. Thirty years ago, the Early Treatment Diabetic Retinopathy Study (ETDRS) demonstrated that focal/grid laser photocoagulation reduces moderate vision loss from DME by 50% or more; thus, macular photocoagulation became the gold standard treatment for DME. However, with the development of anti-VEGF drugs (bevacizumab, ranibizumab, and aflibercept), better outcomes were obtained in terms of visual acuity gain and decrease in macular thickness in some studies when antiangiogenic drugs were administered in monotherapy. Macular laser therapy may still play an important role as an adjuvant treatment because it is able to improve macular thickness outcomes and reduce the number of injections needed. Here, we review some of the clinical trials that have assessed the efficacy of macular laser treatment, either as part of the treatment protocol or as rescue therapy. PMID:28348882

  20. Combination of Anti-VEGF and Laser Photocoagulation for Diabetic Macular Edema: A Review.

    PubMed

    Distefano, Laura N; Garcia-Arumi, Jose; Martinez-Castillo, Vicente; Boixadera, Anna

    2017-01-01

    Diabetic macular edema (DME) is the most common cause of vision loss in diabetic patients. Thirty years ago, the Early Treatment Diabetic Retinopathy Study (ETDRS) demonstrated that focal/grid laser photocoagulation reduces moderate vision loss from DME by 50% or more; thus, macular photocoagulation became the gold standard treatment for DME. However, with the development of anti-VEGF drugs (bevacizumab, ranibizumab, and aflibercept), better outcomes were obtained in terms of visual acuity gain and decrease in macular thickness in some studies when antiangiogenic drugs were administered in monotherapy. Macular laser therapy may still play an important role as an adjuvant treatment because it is able to improve macular thickness outcomes and reduce the number of injections needed. Here, we review some of the clinical trials that have assessed the efficacy of macular laser treatment, either as part of the treatment protocol or as rescue therapy.

  1. Resolution of choroidal neovascularization secondary to punctate inner choroidopathy (PIC) with intravitreal anti-VEGF agents: a case series.

    PubMed

    Mangat, Simran S; Ramasamy, B; Prasad, Som; Walters, Gavin; Mohammed, Moin; Mckibbin, Martin

    2011-01-01

    Case series of four patients with CNVM secondary to PIC treated solely with anti VEGF in three cases and in combination with PDT in the other. This series reveals long term follow up (3 months to 28 months) which is currently not described in the literature.

  2. Transgenic rabbit that expresses a functional human lipoprotein (a)

    DOEpatents

    Rouy, Didier; Duverger, Nicolas; Emmanuel, Florence; Denefle, Patrice; Houdebine, Louis-Marie; Viglietta, Celine; Rubin, Edward M.; Hughes, Steven D.

    2003-01-01

    A transgenic rabbit which has in its genomic DNA sequences that encode apolipoprotein (a) and apolipoprotein B polypeptides which are capable of combining to produce lipoprotein (a), a process for creating such a rabbit, and the use of the rabbit to identify compounds which are effective in the treatment of human diseases which are associated with, induced and/or exacerbated by Lp(a) expression.

  3. Experiences of patients undergoing anti-VEGF treatment for neovascular age-related macular degeneration: a systematic review.

    PubMed

    Boyle, Jessica; Vukicevic, Meri; Koklanis, Konstandina; Itsiopoulos, Catherine

    2015-01-01

    Current therapy to slow disease progression in patients with neovascular age-related macular degeneration (AMD) often entails intra-vitreal injection of an anti-vascular endothelial growth factor (VEGF) agent, that begins with a three-month loading phase of four weekly injections followed by regular monthly visits with clinician-determined re-treatment. The effects of AMD on quality of life and visual function have been extensively reported in the literature, however, less is known about the burden imposed on patients by the arduous and often indefinite treatment schedule which habitually follows a diagnosis of wet AMD. To date, no systematic review has been conducted of research investigating patients' experiences of anti-VEGF treatment for AMD. A systematic search of the Embase, Medline, PsycINFO and PubMed electronic databases was undertaken to identify all studies between January 2004 and December 2013, published in the English language and involving human participants. A hand-search of an additional four journals was conducted. Ten articles were identified for inclusion in this review. A critical appraisal was undertaken using the Critical Appraisal Skills Programme Qualitative Research Checklist and the results synthesised to form a narrative review. Few studies to date have investigated patients' experiences of treatment for AMD. These studies have focused primarily on patients' experiences of the injection procedure with respect to pain and anxiety. Anticipated discomfort is often greater than actual discomfort experienced during intra-vitreal injection. However, different stages of the treatment procedure produce varying levels of patient discomfort. No one method of anaesthesia has consistently been shown to be more effective in reducing discomfort associated with treatment. Common reasons underlying patient apprehension surrounding treatment include the thought of having an injection, fear of losing eyesight and fear of the unknown. Whilst these studies

  4. Efficacy of Anti-VEGF/VEGFR Agents on Animal Models of Endometriosis: A Systematic Review and Meta-Analysis

    PubMed Central

    Liu, Shuangge; Xin, Xiaoyan; Hua, Teng; Shi, Rui; Chi, Shuqi; Jin, Zhishan; Wang, Hongbo

    2016-01-01

    Background/Objective Vascular endothelial growth factor (VEGF) is the most important promotor of angiogenesis. Some studies indicate that anti-angiogenic agents that interfere with VEGF and its receptor (VEGFR), i.e., anti-VEGF/VEGFR agents, may be applied to treat endometriosis. This meta-analysis investigated the efficacy of anti-VEGF/VEGFR agents in animal models of endometriosis. Methods A systematic literature search was performed for animal studies published in English or Chinese from January 1995 to June 2016, which evaluated the effect of anti-VEGF/VEGFR agents on endometriosis. The databases were: PubMed, Web of Science, BIOSIS, Embase, and CNKI. The quality of included studies was assessed using the SYRCLE tool. The random-effect models were used to combine the results of selected studies. Heterogeneity was assessed using H2statistic and I2 statistic. Subgroup analyses were performed to determine the source of heterogeneity in endometriosis scores and follicle numbers. Results We identified 13 studies that used anti-VEGF/VEGFR agents in various animal models. The meta-analysis showed that anti-VEGF/VEGFR agents were associated with smaller size (standardized mean difference (SMD) –0.96, 95% CI –1.31 to –0.62; P < 0.0001) and weight (SMD –1.70, 95% CI –2.75 to –0.65; P = 0.002) of endometriosis lesions, relative to the untreated controls, as well as a lower incidence rate of endometriosis (risk ratio 0.26, 95% CI 0.07 to 0.93; P = 0.038) and endometriosis score (SMD –1.17, 95% CI –1.65 to –0.69; P < 0.0001); the number of follicles were similar (SMD –0.78, 95% CI –1.65 to 0.09; P = 0.08). Conclusions Anti-VEGF/VEGFR agents appeared to inhibit the growth of endometriosis, with no effect on ovarian function. Anti-angiogenic therapy may be a novel strategy in treating endometriosis. PMID:27855197

  5. Experimental studies of a vaccine formulation of recombinant human VEGF antigen with aluminum phosphate

    PubMed Central

    Pérez Sánchez, Lincidio; Morera Díaz, Yanelys; Bequet-Romero, Mónica; Ramses Hernández, Gerardo; Rodríguez, Yadira; Castro Velazco, Jorge; Puente Pérez, Pedro; Ayala Avila, Marta; Gavilondo, Jorge V

    2015-01-01

    CIGB-247 is a cancer vaccine that is a formulation of a recombinant protein antigen representative of the human vascular endothelial growth factor (VEGF) with a bacterially-derived adjuvant (VSSP). The vaccine has shown an excellent safety profile in mice, rats, rabbits, not-human primates and in recent clinical trials in cancer patients. Response to the vaccine is characterized by specific antibody titers that neutralize VEGF/VEGFR2 binding and a cytotoxic tumor-specific response. To expand our present anti-VEGF active immunotherapy strategies, we have now studied in mice and non-human primates the effects of vaccination with a formulation of our recombinant VEGF antigen and aluminum phosphate adjuvant (hereafter denominated CIGB-247-A). Administered bi-weekly, CIGB-247-A produces high titers of anti-VEGF IgG blocking antibodies in 2 mice strains. Particularly in BALB/c, the treatment impaired subcutaneous F3II mammary tumor growth and reduced the number of spontaneous lung macro metastases, increasing animals' survival. Spleen cells from specifically immunized mice directly killed F3II tumor cells in vitro. CIGB-247-A also showed to be immunogenic in non-human primates, which developed anti-VEGF blocking antibodies and the ability for specific direct cell cytotoxic responses, all without impairing the healing of deep skin wounds or other side effect. Our results support consideration of aluminum phosphate as a suitable adjuvant for the development of new vaccine formulations using VEGF as antigen. PMID:25891359

  6. Anti-VEGF treatment of diabetic macular edema in clinical practice: effectiveness and patterns of use (ECHO Study Report 1)

    PubMed Central

    Blinder, Kevin J; Dugel, Pravin U; Chen, Sanford; Jumper, J Michael; Walt, John G; Hollander, David A; Scott, Lanita C

    2017-01-01

    Purpose To evaluate the efficacy, safety, and injection frequency of vascular endothelial growth factor (VEGF) inhibitors as used in clinical practice for the treatment of diabetic macular edema. Methods Multicenter (10 sites), retrospective chart review in patients (n=156) who received ≥3 anti-VEGF injections. Data collected for ≥6 months after the first injection included Snellen best-corrected visual acuity (BCVA) and central retinal thickness (CRT) by time-domain or spectral-domain optical coherence tomography (TD-OCT or SD-OCT). Results Mean number of anti-VEGF injections (627 bevacizumab, 594 ranibizumab, 1 aflibercept) was 5.8 (year 1), 5.0 (year 2), and 3.4 (year 3). Percentage of patients with BCVA of 20/40 or better and CRT ≤250 μm on TD-OCT or ≤300 μm on SD-OCT at the same visit (primary endpoint) ranged from 16.4% to 38.9% after the first 10 injections; 51.9%–62.3% achieved ≥20/40 BCVA and 26.2%–48.0% met CRT criteria. Therapy was well tolerated with 19 treatment-related adverse events (all ocular) reported. Conclusion Anti-VEGF injections were administered less frequently and were less effective than those in the ranibizumab registration trials. After each of the first 9 injections, <25% of patients achieved both BCVA of 20/40 or better and a dry macula. A substantial proportion of patients are suboptimal responders to anti-VEGF therapy; these patients may be candidates for other therapies, including intravitreal corticosteroid and laser therapy. PMID:28260851

  7. Treatment of neovascular age-related macular degeneration with anti-VEGF agents: retrospective analysis of 5-year outcomes

    PubMed Central

    Pedrosa, Ana Catarina; Reis-Silva, Adriana; Pinheiro-Costa, João; Beato, João; Freitas-da-Costa, Paulo; Falcão, Manuel S; Falcão-Reis, Fernando; Carneiro, Ângela

    2016-01-01

    Purpose To evaluate the 5-year results obtained in clinical practice in the treatment of neovascular age-related macular degeneration (nAMD) with anti-VEGF agents. Materials and methods We retrospectively analyzed all patients with nAMD who initiated anti-VEGF treatment before October 2009. We collected data regarding visual and anatomical outcomes. Results A total of 278 patients met the selection criteria. The mean number of intravitreal injections was 5.7 in the first year and 3.7 in the fifth year. A positive mean visual acuity variation of +3.7 Early Treatment Diabetic Retinopathy Study letters occurred in the first year, but no significant differences relative to baseline were observed thereafter. The majority of patients (71%) maintained stable visual acuity throughout follow-up. At 5 years, mean central macular thickness remained substantially inferior to baseline (−96.6 μm), and 56% of patients maintained dry retinas. Conclusion Anti-VEGF therapy leads to long-term visual stabilization in the great majority of patients. PMID:27099460

  8. Predictors of anti-VEGF treatment response in neovascular age-related macular degeneration.

    PubMed

    Finger, Robert P; Wickremasinghe, Sanjeewa S; Baird, Paul N; Guymer, Robyn H

    2014-01-01

    Currently available evidence on predictors of anti-vascular endothelial growth factor (VEGF) treatment response in neovascular age-related macular degeneration was reviewed. No meta-analysis of results is possible because of a lack of controlled and randomized trials, varying treatment regimes and outcome measures used, as well as suboptimal reporting. For genetic factors, most evidence to date has been generated for single nucleotide polymorphisms (SNPs) in the complement factor H (CFH), and VEGF-A genes. Just under half of the SNPs assessed in the CFH gene and 15% of the SNPs assessed in the VEGF gene were found to be associated with visual outcomes or the number of injections required during follow-up. Some evidence suggests association of worse treatment outcomes as well as a younger age at treatment onset with an increasing number of risk alleles in known risk genes (CFH and ARMS2/HTRA1) and polymorphisms in the VEGF-A gene. Clinical factors such as higher age, a better visual acuity (VA), a larger choroidal neovascularization (CNV) lesion at baseline, and a delay between symptom onset and initiation of treatment of more than 3 weeks also impact outcomes. Conversely, a worse acuity at baseline predicted more gain in vision. Overall, patients presenting with good acuity at baseline were more likely to have good VA at follow up, but the gain afforded by treatment was impacted by a ceiling effect. Most available evidence suggests a strong association of clinical factors such as age, baseline VA, and CNV lesion size with anti-VEGF treatment outcomes. No behavioral factors such as smoking influence treatment outcomes. Based on the studies conducted so far, the evidence suggests that underlying genotype of known AMD risk associated genes or of the VEGF-A gene have a limited effect, whereas presenting clinical factors appear to be more important in determining treatment outcomes.

  9. Attaching and effacing activities of rabbit and human enteropathogenic Escherichia coli in pig and rabbit intestines.

    PubMed Central

    Moon, H W; Whipp, S C; Argenzio, R A; Levine, M M; Giannella, R A

    1983-01-01

    Three strains of enteropathogenic Escherichia coli (EPEC), originally isolated from humans and previously shown to cause diarrhea in human volunteers by unknown mechanisms, and one rabbit EPEC strain were shown to attach intimately to and efface microvilli and cytoplasm from intestinal epithelial cells in both the pig and rabbit intestine. The attaching and effacing activities of these EPEC were demonstrable by light microscopic examination of routine histological sections and by transmission electron microscopy. It was suggested that intact colostrum-deprived newborn pigs and ligated intestinal loops in pigs and rabbits may be useful systems to detect EPEC that have attaching and effacing activities and for studying the pathogenesis of such infections. The lesions (attachment and effacement) produced by EPEC in these systems were multifocal, with considerable animal-to-animal variation in response to the same strain of EPEC. The EPEC strains also varied in the frequency and extent of lesion production. For example, three human EPEC strains usually caused extensive lesions in rabbit intestinal loops, whereas two other human EPEC strains usually did not produce lesions in this system. Images PMID:6350186

  10. Improved tumor vascularization after anti-VEGF therapy with carboplatin and nab-paclitaxel associates with survival in lung cancer

    PubMed Central

    Heist, Rebecca S.; Duda, Dan G.; Sahani, Dushyant V.; Ancukiewicz, Marek; Fidias, Panos; Sequist, Lecia V.; Temel, Jennifer S.; Shaw, Alice T.; Pennell, Nathan A.; Neal, Joel W.; Gandhi, Leena; Lynch, Thomas J.; Engelman, Jeffrey A.; Jain, Rakesh K.

    2015-01-01

    Addition of anti-VEGF antibody therapy to standard chemotherapies has improved survival and is an accepted standard of care for advanced non–small cell lung cancer (NSCLC). However, the mechanisms by which anti-VEGF therapy increases survival remain unclear. We evaluated dynamic CT-based vascular parameters and plasma cytokines after bevacizumab alone and after bevacizumab plus chemotherapy with carboplatin and nab-paclitaxel in advanced NSCLC patients to explore potential biomarkers of treatment response and resistance to this regimen. Thirty-six patients were enrolled in this study. The primary end point was 6-mo progression-free survival rate, which was 74% (95% CI: 57, 97). This regimen has a promising overall response rate of 36% and median time to progression of 8.5 (6.0, 38.7) mo and overall survival of 12.2 (9.6, 44.1) mo. We found that anti-VEGF therapy led to a sustained increase in plasma PlGF, a potential pharmacodynamic marker. We also found that higher levels of soluble VEGFR1 measured before starting bevacizumab with chemotherapy were associated with worse survival, supporting its potential role as biomarker of treatment resistance. Our imaging biomarker studies indicate that bevacizumab-based treatment—while reducing blood flow, volume, and permeability in the overall population—may be associated with improved survival in patients with improved tumor vasculature and blood perfusion after treatment. This hypothesis-generating study supports the notion that excessively decreasing vascular permeability and pruning/rarefaction after bevacizumab therapy may negatively impact the outcome of combination therapy in NSCLC patients. This hypothesis warrants further dose-titration studies of bevacizumab to examine the dose effect on tumor vasculature and treatment efficacy. PMID:25605928

  11. Common variant in VEGFA and response to anti-VEGF therapy for neovascular age-related macular degeneration.

    PubMed

    Zhao, L; Grob, S; Avery, R; Kimura, A; Pieramici, D; Lee, J; Rabena, M; Ortiz, S; Quach, J; Cao, G; Luo, H; Zhang, M; Pei, M; Song, Y; Tornambe, P; Goldbaum, M; Ferreyra, H; Kozak, I; Zhang, K

    2013-07-01

    Age-related macular degeneration (AMD) is a leading cause of visual impairment in aging populations in industrialized countries. Here we investigated whether the genotype of vascular endothelial growth factor A (VEGFA) gene is associated with response to anti-VEGF therapy. 223 eyes with neovascular AMD were treated with intravitreal anti-VEGF therapy. Responders were defined as patients who had an improvement in best corrected visual acuity (BCVA) of at least 5 letters or one line on the EDTRS visual acuity chart along with resolution of intraretinal or subretinal fluid over 12 months. Patients who did not meet the definition of responders were classified as poor-responders. The vision of responders (n = 148) improved while the vision of poor-responders (n = 75) worsened (P<0.001). Responders on average had a decrease in central foveal thickness (CFT), while poor-responders had an increase in CFT (P <0.001). Compared with the responder group, the poor-responder group had a higher frequency of the risk (T) allele (Allelic P = 0.019) and TT genotype (P = 0.002 under a recessive model) for the VEGFA-rs943080 polymorphism. VEGFA expression was 1.8-fold higher in cells with the VEGFA rs943080 TT genotype than in cells with the VEGFA rs943080 CC genotype (P = 0.012). Age, gender, smoking, diabetes mellitus, and hypertension did not play a significant role in treatment response, but BMI was found to be significantly different between responders and poorresponders (P = 0.033). In conclusion, we demonstrated a potential pharmacogenetic relationship between the VEGFA gene and treatment response to anti-VEGF therapy.The studies are registered at ClinicalTrials.gov under the identifiers NCT00474695 (http://clinicaltrials. gov/ct2/show/NCT00474695) and NCT01464723 (http://clinicaltrials.gov/ct2/show/NCT01464723).

  12. Optimizing the Anti-VEGF Treatment Strategy for Neovascular Age-Related Macular Degeneration: From Clinical Trials to Real-Life Requirements.

    PubMed

    Mantel, Irmela

    2015-06-01

    This Perspective discusses the pertinence of variable dosing regimens with anti-vascular endothelial growth factor (VEGF) for neovascular age-related macular degeneration (nAMD) with regard to real-life requirements. After the initial pivotal trials of anti-VEGF therapy, the variable dosing regimens pro re nata (PRN), Treat-and-Extend, and Observe-and-Plan, a recently introduced regimen, aimed to optimize the anti-VEGF treatment strategy for nAMD. The PRN regimen showed good visual results but requires monthly monitoring visits and can therefore be difficult to implement. Moreover, application of the PRN regimen revealed inferior results in real-life circumstances due to problems with resource allocation. The Treat-and-Extend regimen uses an interval based approach and has become widely accepted for its ease of preplanning and the reduced number of office visits required. The parallel development of the Observe-and-Plan regimen demonstrated that the future need for retreatment (interval) could be reliably predicted. Studies investigating the observe-and-plan regimen also showed that this could be used in individualized fixed treatment plans, allowing for dramatically reduced clinical burden and good outcomes, thus meeting the real life requirements. This progressive development of variable dosing regimens is a response to the real-life circumstances of limited human, technical, and financial resources. This includes an individualized treatment approach, optimization of the number of retreatments, a minimal number of monitoring visits, and ease of planning ahead. The Observe-and-Plan regimen achieves this goal with good functional results. Translational Relevance: This perspective reviews the process from the pivotal clinical trials to the development of treatment regimens which are adjusted to real life requirements. The article discusses this translational process which- although not the classical interpretation of translation from fundamental to clinical research

  13. The quantitation of C6 in rabbit and human sera

    PubMed Central

    Tedesco, F.; Lachmann, P. J.

    1971-01-01

    C6 quantitation was carried out in rabbit and human sera by the single radial immunodiffusion technique. The C6 content of the rabbit and human sera used as standards was estimated by precipitin analysis, using an anti-C6 antiserum labelled with 125I. The mean C6 level in normal human serum was 11 μg/ml, whereas in normal rabbit serum it was 35 μg/ml. Sera from forty rabbits heterozygous for C6 deficiency were found to have a mean concentration of C6 of 14 μg/ml. The C6 level was estimated in sera from patients with various immunological disorders and found to be significantly higher in the sera from patients with rheumatoid arthritis and normal in the sera from patients with SLE, glomerulonephritis, nephrotic syndrome and myeloma. C6 haemolytic assays were found to correlate well with the antigenic assays only in fresh sera. In various circumstances this correlation breaks down, presumably because of C6 inactivator. This inactivator, in contrast to C3-inactivator, appears to be bound to antigen–antibody complement complexes. ImagesFig. 2Fig. 3 PMID:4998970

  14. Anti-EGFR and anti-VEGF agents: important targeted therapies of colorectal liver metastases.

    PubMed

    Feng, Qing-Yang; Wei, Ye; Chen, Jing-Wen; Chang, Wen-Ju; Ye, Le-Chi; Zhu, De-Xiang; Xu, Jian-Min

    2014-04-21

    Colorectal liver metastasis (CLM) is common worldwide. Targeted therapies with monoclonal antibodies have been proven effective in numerous clinical trials, and are now becoming standards for patients with CLM. The development and application of anti-epidermal growth factor receptor (anti-EGFR) and anti-vascular endothelial growth factor (anti-VEGF) antibodies represents significant advances in the treatment of this disease. However, new findings continue to emerge casting doubt on the efficacy of this approach. The Kirsten rat sarcoma viral oncogene (KRAS) has been proven to be a crucial predictor of the success of anti-EGFR treatment in CLM. Whereas a recent study summarized several randomized controlled trials, and showed that patients with the KRAS G13D mutation significantly benefited from the addition of cetuximab in terms of progress-free survival (PFS, 4.0 mo vs 1.9 mo, HR = 0.51, P = 0.004) and overall survival (OS, 7.6 mo vs 5.7 mo, HR = 0.50, P = 0.005). Some other studies also reported that the KRAS G13D mutation might not be absolutely predictive of non-responsiveness to anti-EGFR therapy. At the same time, "new" RAS mutations, including mutations in neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS) and exons 3 and 4 of KRAS, have been suggested to be predictors of a poor treatment response. This finding was first reported by the update of the PRIME trial. The update showed that for patients with non-mutated KRAS exon 2 but other RAS mutations, panitumumab-fluorouracil, leucovorin, and oxaliplatin (FOLFOX)4 treatment led to inferior PFS (HR = 1.28, 95%CI: 0.79-2.07) and OS (HR = 1.29, 95%CI: 0.79-2.10), which was consistent with the findings in patients with KRAS mutations in exon 2. Then, the update of the PEAK trial and the FIRE-III trial also supported this finding, which would reduce candidates for anti-EGFR therapy but enhance the efficacy. In first-line targeted combination therapy, the regimens of cetuximab plus FOLFOX was called into

  15. Endoglin and activin receptor-like kinase 1 heterozygous mice have a distinct pulmonary and hepatic angiogenic profile and response to anti-VEGF treatment.

    PubMed

    Ardelean, Daniela S; Jerkic, Mirjana; Yin, Melissa; Peter, Madonna; Ngan, Bo; Kerbel, Robert S; Foster, F Stuart; Letarte, Michelle

    2014-01-01

    Hereditary hemorrhagic telangiectasia (HHT) is a vascular dysplasia associated with dysregulated angiogenesis and arteriovascular malformations. The disease is caused by mutations in endoglin (ENG; HHT1) or activin receptor-like kinase 1 (ALK1; HHT2) genes, coding for transforming growth factor β (TGF-β) superfamily receptors. Vascular endothelial growth factor (VEGF) has been implicated in HHT and beneficial effects of anti-VEGF treatment were recently reported in HHT patients. To investigate the systemic angiogenic phenotype of Endoglin and Alk1 mutant mice and their response to anti-VEGF therapy, we assessed microvessel density (MVD) in multiple organs after treatment with an antibody to mouse VEGF or vehicle. Lungs were the only organ showing an angiogenic defect, with reduced peripheral MVD and secondary right ventricular hypertrophy (RVH), yet distinctly associated with a fourfold increase in thrombospondin-1 (TSP-1) in Eng (+/-) versus a rise in angiopoietin-2 (Ang-2) in Alk1 (+/-) mice. Anti-VEGF treatment did reduce lung VEGF levels but interestingly, led to an increase in peripheral pulmonary MVD and attenuation of RVH; it also normalized TSP-1 and Ang-2 expression. Hepatic MVD, unaffected in mutant mice, was reduced by anti-VEGF therapy in heterozygous and wild type mice, indicating a liver-specific effect of treatment. Contrast-enhanced micro-ultrasound demonstrated a reduction in hepatic microvascular perfusion after anti-VEGF treatment only in Eng (+/-) mice. Our findings indicate that the mechanisms responsible for the angiogenic imbalance and the response to anti-VEGF therapy differ between Eng and Alk1 heterozygous mice and raise the need for systemic monitoring of anti-angiogenic therapy effects in HHT patients.

  16. A Quantitative Approach to Predict Differential Effects of Anti-VEGF Treatment on Diffuse and Focal Leakage in Patients with Diabetic Macular Edema: A Pilot Study

    PubMed Central

    Allingham, Michael J.; Mukherjee, Dibyendu; Lally, Erin B.; Rabbani, Hossein; Mettu, Priyatham S.; Cousins, Scott W.; Farsiu, Sina

    2017-01-01

    Purpose We use semiautomated segmentation of fluorescein angiography (FA) to determine whether anti-vascular endothelial growth factor (VEGF) treatment for diabetic macular edema (DME) differentially affects microaneurysm (MA)–associated leakage, termed focal leakage, versus non-MA–associated leakage, termed diffuse leakage. Methods We performed a retrospective study of 29 subjects treated with at least three consecutive injections of anti-VEGF agents for DME (mean 4.6 injections; range, 3–10) who underwent Heidelberg FA before and after anti-VEGF therapy. Inclusion criteria were macula center involving DME and at least 3 consecutive anti-VEGF injections. Exclusion criteria were macular edema due to cause besides DME, anti-VEGF within 3 months of initial FA, concurrent treatment for DME besides anti-VEGF, and macular photocoagulation within 1 year. At each time point, total leakage was semiautomatically segmented using a modified version of our previously published software. Microaneurysms were identified by an expert grader and leakage within a 117 μm radius of each MA was classified as focal leakage. Remaining leakage was classified as diffuse leakage. The absolute and percent changes in total, diffuse, and focal leakage were calculated for each subject. Results Mean pretreatment total leakage was 8.2 mm2 and decreased by a mean of 40.1% (P < 0.0001; 95% confidence interval [CI], [−28.6, −52.5]) following treatment. Diffuse leakage decreased by a mean of 45.5% (P < 0.0001; 95% CI, [−31.3, −59.6]) while focal leakage decreased by 17.9% (P = 0.02; 95% CI, [−1.0, −34.8]). The difference in treatment response between focal and diffuse leakage was statistically significant (P = 0.01). Conclusions Anti-VEGF treatment for DME results in decreased diffuse leakage but had relatively little effect on focal leakage as assessed by FA. This suggests that diffuse leakage may be a marker of VEGF-mediated pathobiology. Patients with predominantly focal leakage

  17. Disposition of human fibrinopeptide A in normal and nephrectomized rabbits

    SciTech Connect

    Harenberg, J.; Stehle, G.; Waibel, S.; Hermann, H.J.; Eisenhut, M.; Zimmermann, R.

    1983-10-01

    The distribution, elimination, and metabolism of human fibrinopeptide A (FPA) were studied in normal and nephrectomized rabbits. The activity of /sup 125/I-labeled desamino-tyrosyl human FPA (DAT-FPA) was followed over 4 hours after i.v. administration. Results show that in normal rabbits (n . 10) DAT-FPA is eliminated from plasma in four phases with half-lives of 30 sec, 3.5 min, 15 min, and 90 min. The distribution of /sup 123/I-labeled DAT-FPA in plasma was determined in 15 control rabbits with scintigraphy over 2 hours. DAT-FPA was distributed primarily in the cardiovascular system, liver, and kidneys. In some animals minimal radioactivity was detected over the gall bladder. Radioactivity accumulated rapidly in the urinary bladder, approximately 50% being recorded after 15 min and 90% after 120 min. In the heart area radioactivity decreased with half-lives of 25 sec, 7.5 min, 25 min, and 180 min. Nephrectomized rabbits had similar initial fast distribution of DAT-FPA after administration of /sup 125/I-labeled (n . 10) and /sup 123/I-labeled peptide (n . 10). The estimated half-life of the slow component was in the order of several hours. The results of the scintigraphic and gel chromatographic studies show that FPA is primarily excreted in the urine. Previously reported half-lives of FPA reflect distribution rather than steady state conditions.

  18. Rabbit models for the study of human atherosclerosis: from pathophysiological mechanisms to translational medicine.

    PubMed

    Fan, Jianglin; Kitajima, Shuji; Watanabe, Teruo; Xu, Jie; Zhang, Jifeng; Liu, Enqi; Chen, Y Eugene

    2015-02-01

    Laboratory animal models play an important role in the study of human diseases. Using appropriate animals is critical not only for basic research but also for the development of therapeutics and diagnostic tools. Rabbits are widely used for the study of human atherosclerosis. Because rabbits have a unique feature of lipoprotein metabolism (like humans but unlike rodents) and are sensitive to a cholesterol diet, rabbit models have not only provided many insights into the pathogenesis and development of human atherosclerosis but also made a great contribution to translational research. In fact, rabbit was the first animal model used for studying human atherosclerosis, more than a century ago. Currently, three types of rabbit model are commonly used for the study of human atherosclerosis and lipid metabolism: (1) cholesterol-fed rabbits, (2) Watanabe heritable hyperlipidemic rabbits, analogous to human familial hypercholesterolemia due to genetic deficiency of LDL receptors, and (3) genetically modified (transgenic and knock-out) rabbits. Despite their importance, compared with the mouse, the most widely used laboratory animal model nowadays, the use of rabbit models is still limited. In this review, we focus on the features of rabbit lipoprotein metabolism and pathology of atherosclerotic lesions that make it the optimal model for human atherosclerotic disease, especially for the translational medicine. For the sake of clarity, the review is not an attempt to be completely inclusive, but instead attempts to summarize substantial information concisely and provide a guideline for experiments using rabbits.

  19. A new algorithm for a better characterization and timing of the anti-VEGF vascular effect named "normalization".

    PubMed

    El Alaoui-Lasmaili, Karima; Djermoune, El-Hadi; Tylcz, Jean-Baptiste; Meng, Dominique; Plénat, François; Thomas, Noémie; Faivre, Béatrice

    2017-02-01

    Antiangiogenics are widely used in cancer treatment in combination with chemotherapy and radiotherapy for their vascular effects. Antiangiogenics are supposed to induce morphological and functional changes in the chaotic tumor vasculature that would help enhance the therapeutic efficacy of chemotherapy and radiotherapy through the amelioration of the drug delivery or the oxygenation in the tumor, respectively. However, finding the best treatment sequence is not an easy task to achieve and no consensus has yet been established because of the lack of knowledge regarding when and for how long the vascular network is ameliorated. The aim of this work was to develop a dedicated image processing algorithm able to analyze the vascular structures on optical microscopy images of the vascular network and to follow its fine modifications in vivo, over time. We applied this algorithm to follow the evolution of the vascular parameters (vascularized tissue surface, branches, sprouts and length), in response or not to anti-VEGF therapy (10 mg/kg/day) and determine precisely whether there is really a vascular "normalization" with anti-VEGF therapy in comparison with the parameters extracted from healthy vascular networks. We found that for this determination, the choice of region of interest to analyze is critical as it is important to compare only microcirculation areas and avoid areas with arteriole-venule-capillary hierarchy. The algorithm analysis allowed us to define a vascular "normalization" in treated tumors, between 8 and 12 days of bevacizumab treatment that was confirmed by standard immunohistochemical analysis, microvascular permeability assessment and immunohistological blood perfusion assessment.

  20. Post-intravitreal anti-VEGF endophthalmitis in the United Kingdom: incidence, features, risk factors, and outcomes

    PubMed Central

    Lyall, D A M; Tey, A; Foot, B; Roxburgh, S T D; Virdi, M; Robertson, C; MacEwen, C J

    2012-01-01

    Purpose To describe the incidence, features, management, and risk factors of post-intravitreal anti-VEGF endophthalmitis (PIAE) in patients undergoing treatment for exudative age-related macular degeneration in the United Kingdom. Methods Prospective observational case control study. Forty-seven cases of PIAE were identified through the British Ophthalmological Surveillance Unit from January 2009 to March 2010. Data collected at diagnosis and at 6 months follow-up included patient demographics, intravitreal injection details, pre- and post-injection management, visual acuity, clinical features and management of PIAE, causative organisms, and clinical outcomes. Details were compared with 200 control cases from 10 control centres to identify potential risk factors. Results Estimated PIAE was 0.025%. Culture-positive PIAE incidence was 0.015%. Mean age of presentation was 78 years. Mean number of intravitreal injections before PIAE was 5. Mean days to presentation was 5 (range 1–39). Positive microbiology culture was found in 59.6%. The majority of causative organisms were Gram positive (92.8%). Significant risk factors were failure to administer topical antibiotics immediately after the injection (P=0.001), blepharitis (P=0.006), subconjunctival anaesthesia (P=0.021), patient squeezing during the injection (P=0.021), and failure to administer topical antibiotics before anti-VEGF injection (P=0.05). Discussion The incidence of PIAE in the United Kingdom is comparable to other studies at a rate of 0.025%. The most common causative organisms were Gram positive. Measures to minimise the risk of PIAE include treatment of blepharitis before injection, avoidance of subconjunctival anaesthesia, topical antibiotic administration immediately after injection with consideration to administering topical antibiotics before injection. PMID:23060022

  1. Profiling Analysis of Histone Modifications and Gene Expression in Lewis Lung Carcinoma Murine Cells Resistant to Anti-VEGF Treatment

    PubMed Central

    Du, Yanhua; Chen, Kaiming; Liu, Zhenping; Li, Bing; Li, Jie; Tao, Fei; Gu, Hua; Jiang, Cizhong; Fang, Jianmin

    2016-01-01

    Tumor cells become resistant after long-term use of anti-VEGF (vascular endothelial growth factor) agents. Our previous study shows that treatment with a VEGF inhibitor (VEGF-Trap) facilitates to develop tumor resistance through regulating angiogenesis-related genes. However, the underlying molecular mechanisms remain elusive. Histone modifications as a key epigenetic factor play a critical role in regulation of gene expression. Here, we explore the potential epigenetic gene regulatory functions of key histone modifications during tumor resistance in a mouse Lewis lung carcinoma (LLC) cell line. We generated high resolution genome-wide maps of key histone modifications in sensitive tumor sample (LLC-NR) and resistant tumor sample (LLC-R) after VEGF-Trap treatment. Profiling analysis of histone modifications shows that histone modification levels are effectively predictive for gene expression. Composition of promoters classified by histone modification state is different between LLC-NR and LLC-R cell lines regardless of CpG content. Histone modification state change between LLC-NR and LLC-R cell lines shows different patterns in CpG-rich and CpG-poor promoters. As a consequence, genes with different level of CpG content whose gene expression level are altered are enriched in distinct functions. Notably, histone modification state change in promoters of angiogenesis-related genes consists with their expression alteration. Taken together, our findings suggest that treatment with anti-VEGF therapy results in extensive histone modification state change in promoters with multiple functions, particularly, biological processes related to angiogenesis, likely contributing to tumor resistance development. PMID:27362259

  2. A clinical study to evaluate the efficacy of intravitreal Anti-VEGF therapy in treating macular edema due to retinal venous occlusions

    PubMed Central

    Kumar, Poninder; Banarji, Ajay; Patyal, Sagarika; Gurunadh, V.S.; Ahluwalia, T.S.; Oli, Avadesh; Moulick, P.S.; Makker, Anuradha

    2013-01-01

    Background A non-randomized, interventional study was carried out various types of retinal venous occlusions with significant macular edema who required an Anti-VEGF injection. Method One hundred and one consecutive patients diagnosed as a case of CRVO/HCRVO/BRVO were enrolled in the study provided they had significant macular edema. Atleast three intra-vitreal injections of Anti-VEGFs were given and both the pre and post injections BCVA and CMT on OCT were observed and analyzed. Results 87 patients (86.14%) showed a significant improvement of vision of atleast two lines on the Snellen's and mean BCVA improved from log MAR +1.084 to log MAR +0.455. CMT on OCT showed reduction in thickness after Anti-VEGF therapy in 99 patients out of 101 and mean CMT decreased from 586.30 μ at baseline to 329.50 μ. Both of these findings were statistically very significant. Conclusions Anti-VEGF therapy had a marked improvement in BCVA along with a dramatic reduction in CMT in the vast majority of RVOs patients with no serious ocular or systemic side effects. PMID:24600120

  3. Detection of aqueous VEGF concentrations before and after intravitreal injection of anti-VEGF antibody using low-volume sampling paper-based ELISA.

    PubMed

    Hsu, Min-Yen; Hung, Yu-Chien; Hwang, De-Kuang; Lin, Shang-Chi; Lin, Keng-Hung; Wang, Chun-Yuan; Choi, Hin-Yeung; Wang, Yu-Ping; Cheng, Chao-Min

    2016-10-11

    Intraocular vascular endothelial growth factor (VEGF) levels play an important role in the pathogenesis of blindness-related diseases, such as age-related macular degeneration (AMD). Here, we aimed to develop a paper-based enzyme-linked immunosorbent assay (P-ELISA) to analyze the suppression of aqueous VEGF concentrations following intravitreal injection (IVI) of anti-VEGF antibody (bevacizumab or ranibizumab). A total of 25 eyes with wet AMD, one with myopic neovascularization, and one with polypoidal choroidal vasculopathy were enrolled in this study. The limit of detection using P-ELISA was 0.03 pg/mL. Forty-six consecutive samples of aqueous humor were acquired. From all samples, 66.67% (10/15) achieved complete VEGF suppression (below the detection limit) within 5 weeks of receiving IVI of anti-VEGF antibody. Only 13.33% of samples (2/15) achieved complete VEGF suppression 5 weeks after receiving treatment. In some patients, elevated VEGF was still detected 5 weeks after receipt of anti-VEGF antibody, and all samples (10/10) were found to have elevated VEGF levels 49 days after treatment. Thus, we suggest that monthly IVI of anti-VEGF antibody may be required to ensure durable VEGF inhibition. Ultrasensitive P-ELISA can detect elevated VEGF at an earlier time point and may facilitate decision-making regarding appropriate treatment strategies.

  4. Detection of aqueous VEGF concentrations before and after intravitreal injection of anti-VEGF antibody using low-volume sampling paper-based ELISA

    PubMed Central

    Hsu, Min-Yen; Hung, Yu-Chien; Hwang, De-Kuang; Lin, Shang-Chi; Lin, Keng-Hung; Wang, Chun-Yuan; Choi, Hin-Yeung; Wang, Yu-Ping; Cheng, Chao-Min

    2016-01-01

    Intraocular vascular endothelial growth factor (VEGF) levels play an important role in the pathogenesis of blindness-related diseases, such as age-related macular degeneration (AMD). Here, we aimed to develop a paper-based enzyme-linked immunosorbent assay (P-ELISA) to analyze the suppression of aqueous VEGF concentrations following intravitreal injection (IVI) of anti-VEGF antibody (bevacizumab or ranibizumab). A total of 25 eyes with wet AMD, one with myopic neovascularization, and one with polypoidal choroidal vasculopathy were enrolled in this study. The limit of detection using P-ELISA was 0.03 pg/mL. Forty-six consecutive samples of aqueous humor were acquired. From all samples, 66.67% (10/15) achieved complete VEGF suppression (below the detection limit) within 5 weeks of receiving IVI of anti-VEGF antibody. Only 13.33% of samples (2/15) achieved complete VEGF suppression 5 weeks after receiving treatment. In some patients, elevated VEGF was still detected 5 weeks after receipt of anti-VEGF antibody, and all samples (10/10) were found to have elevated VEGF levels 49 days after treatment. Thus, we suggest that monthly IVI of anti-VEGF antibody may be required to ensure durable VEGF inhibition. Ultrasensitive P-ELISA can detect elevated VEGF at an earlier time point and may facilitate decision-making regarding appropriate treatment strategies. PMID:27725716

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

    PubMed

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

    2014-09-01

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

  6. Pharmacokinetics of mitomycin C in rabbit and human.

    PubMed

    van Hazel, G A; Kovach, J S

    1982-01-01

    A sensitive and specific high-pressure liquid chromatographic assay was developed to characterize the plasma elimination and urinary excretion of mitomycin C in humans. Extraction of mitomycin C and an internal standard, porfiromycin, from plasma by chromatography over a non-ionic resin, Porapak Q, yields high recovery of both compounds and facilitates measurement of as little as 5 ng mitomycin C by reversed-phase high-pressure liquid chromatography. The assay was used to characterize the plasma elimination of mitomycin C in rabbits and was shown to be applicable to the characterization of the pharmacokinetics of mitomycin C in humans receiving as little as 8 mg/m2.

  7. Hepatitis E Virus: First Description in a Pet House Rabbit. A New Transmission Route for Human?

    PubMed

    Caruso, C; Modesto, P; Prato, R; Scaglione, F E; De Marco, L; Bollo, E; Acutis, P L; Masoero, L; Peletto, S

    2015-06-01

    In this work, we identified for the first time hepatitis E virus (HEV) in a pet house rabbit, an adult 7 years old female of domestic rabbit (Oryctolagus cuniculus). Importantly, the resulting phylogenetic tree showed that the HEV strain identified in the pet house rabbit was closely related to a human HEV sequence; this finding reawakens concerns regarding the zoonotic risk represented by HEV in animals and expands to house rabbit the spectrum of potential source of infection for humans. Potential for domestic transmission of HEV to humans should be taken into account.

  8. Gene Therapy with Endogenous Inhibitors of Angiogenesis for Neovascular Age-Related Macular Degeneration: Beyond Anti-VEGF Therapy.

    PubMed

    Prea, Selwyn M; Chan, Elsa C; Dusting, Gregory J; Vingrys, Algis J; Bui, Bang V; Liu, Guei-Sheung

    2015-01-01

    Age-related macular degeneration (AMD) is the leading cause of substantial and irreversible vision loss amongst elderly populations in industrialized countries. The advanced neovascular (or "wet") form of the disease is responsible for severe and aggressive loss of central vision. Current treatments aim to seal off leaky blood vessels via laser therapy or to suppress vessel leakage and neovascular growth through intraocular injections of antibodies that target vascular endothelial growth factor (VEGF). However, the long-term success of anti-VEGF therapy can be hampered by limitations such as low or variable efficacy, high frequency of administration (usually monthly), potentially serious side effects, and, most importantly, loss of efficacy with prolonged treatment. Gene transfer of endogenous antiangiogenic proteins is an alternative approach that has the potential to provide long-term suppression of neovascularization and/or excessive vascular leakage in the eye. Preclinical studies of gene transfer in a large animal model have provided impressive preliminary results with a number of transgenes. In addition, a clinical trial in patients suffering from advanced neovascular AMD has provided proof-of-concept for successful gene transfer. In this mini review, we summarize current theories pertaining to the application of gene therapy for neovascular AMD and the potential benefits when used in conjunction with endogenous antiangiogenic proteins.

  9. Combination of Navigated Macular Laser Photocoagulation and Anti-VEGF Therapy: Precise Treatment for Macular Edema under Dry Retinal Conditions

    PubMed Central

    2017-01-01

    Purpose. To compare the controllability of navigated macular laser photocoagulation (MLP) in dry versus edematous retina and validate that pretreatment diagnostic images can be used as basis for navigated MLP after the macular edema (ME) has been resolved. Materials and Methods. Group 1 was divided into subgroup 1 (dry retina MLP) and subgroup 2 (MLP in ME) for comparisons of laser-burn diameters. In group 2, the areas and locations of ME before an intravitreal injection of anti-VEGF (IVAV) were compared with those of recurrent ME. Results. The average actual diameter as percentage of planned diameter of laser burn in subgroup 1 (11 DME eyes, 6 BRVO eyes) versus subgroup 2 (5 DME eyes, 8 BRVO eyes) was 115.1 ± 9.1% versus 167.2 ± 13.8% (based on retro-mode scanning laser ophthalmoscopy), and 118.1 ± 14.8% versus 176.1 ± 11.6% (based on OCT) (p < 0.001). In group 2 (6 DME eyes, 6 BRVO eyes), difference in mean ME area before IVAV and that in recurrent edema was insignificant (p > 0.05). Conclusion. The controllability of navigated MLP in dry retina is improved compared to edematous retina. This study validates that pretreatment diagnostic images can be used as basis for navigated MLP after the edema has been resolved. PMID:28316837

  10. The era of anti-vascular endothelial growth factor (VEGF) drugs in ophthalmology, VEGF and anti-VEGF therapy

    PubMed Central

    Pożarowska, Dorota

    2016-01-01

    Angiogenesis is a clue process for tissue development and function, both in normal and pathological conditions. This process is regulated by multiple molecular systems. One of the most potent is vascular endothelial growth factor (VEGF) and its receptor (VEGFR) system. Members of this family are involved in new vessel formation in embryogenesis and maturation, as well as in reparative or pathological reactions in later stages. They play a substantial role in regeneration, inflammation, wound healing, as well as in cancer pathology. Nowadays it is possible to modulate VEGF-VEGFR interactions in many pathological conditions using anti-VEGF therapy. This therapy has already achieved a grounded position in the management of rheumatological disorders, tumour progression, and metastasis. Such drugs as bevacizumab, ranibizumab, aflibercept, and pegaptanib have also proven to be very effective in the treatment of several ocular diseases, such as age-related macular degeneration (AMD), macular oedema, or proliferative retinopathies and iris neovascularisation. The indications for the application of this therapy in ophthalmology are becoming wider and wider. It may also be used for corneal pathologies and in anti-glaucoma procedures. PMID:27833450

  11. Src inhibitor reduces permeability without disturbing vascularization and prevents bone destruction in steroid-associated osteonecrotic lesions in rabbits.

    PubMed

    He, Yi-Xin; Liu, Jin; Guo, Baosheng; Wang, Yi-Xiang; Pan, Xiaohua; Li, Defang; Tang, Tao; Chen, Yang; Peng, Songlin; Bian, Zhaoxiang; Liang, Zicai; Zhang, Bao-Ting; Lu, Aiping; Zhang, Ge

    2015-03-09

    To examine the therapeutic effect of Src inhibitor on the VEGF mediating vascular hyperpermeability and bone destruction within steroid-associated osteonecrotic lesions in rabbits. Rabbits with high risk for progress to destructive repair in steroid-associated osteonecrosis were selected according to our published protocol. The selected rabbits were systemically administrated with either Anti-VEGF antibody (Anti-VEGF Group) or Src inhibitor (Src-Inhibition Group) or VEGF (VEGF-Supplement Group) or a combination of VEGF and Src inhibitor (Supplement &Inhibition Group) or control vehicle (Control Group) for 4 weeks. At 0, 2 and 4 weeks after administration, in vivo dynamic MRI, micro-CT based-angiography, histomorphometry and immunoblotting were employed to evaluate the vascular and skeletal events in different groups. The incidence of the destructive repair in the Anti-VEGF Group, Src-Inhibition Group and Supplement &Inhibition Group was all significantly lower than that in the Control Group. The angiogenesis was promoted in VEGF-Supplement Group, Src-Inhibition Group and Supplement &Inhibition Group, while the hyperpermeability was inhibited in Anti-VEGF Group, Src-Inhibition Group and Supplement &Inhibition Group. The trabecular structure was improved in Src-Inhibition Group and Supplement &Inhibition Group. Src inhibitor could reduce permeability without disturbing vascularization and prevent destructive repair in steroid-associated osteonecrosis.

  12. Hepatitis E virus strains in rabbits and evidence of a closely related strain in humans, France.

    PubMed

    Izopet, Jacques; Dubois, Martine; Bertagnoli, Stéphane; Lhomme, Sébastien; Marchandeau, Stéphane; Boucher, Samuel; Kamar, Nassim; Abravanel, Florence; Guérin, Jean-Luc

    2012-08-01

    Hepatitis E virus (HEV) strains from rabbits indicate that these mammals may be a reservoir for HEVs that cause infection in humans. To determine HEV prevalence in rabbits and the strains' genetic characteristics, we tested bile, liver, and additional samples from farmed and wild rabbits in France. We detected HEV RNA in 7% (14/200) of bile samples from farmed rabbits (in 2009) and in 23% (47/205) of liver samples from wild rabbits (in 2007-2010). Full-length genomic sequences indicated that all rabbit strains belonged to the same clade (nucleotide sequences 72.2%-78.2% identical to HEV genotypes 1-4). Comparison with HEV sequences of human strains and reference sequences identified a human strain closely related to rabbit strain HEV. We found a 93-nt insertion in the X domain of open reading frame 1 of the human strain and all rabbit HEV strains. These findings indicate that the host range of HEV in Europe is expanding and that zoonotic transmission of HEV from rabbits is possible.

  13. Effect of anti-VEGF drugs combined with photodynamic therapy in the treatment of age-related macular degeneration.

    PubMed

    Dong, Yi; Wan, Guangming; Yan, Panshi; Chen, Yue; Wang, Wenzhan; Peng, Guanghua

    2016-12-01

    We analyzed the effects of anti-vascular endothelial growth factor (VEGF) drugs combined with photodynamic therapy (PDT) in the treatment of age-related macular degeneration (AMD). Ninety-six cases (192 eyes) of AMD were included in this study and randomly divided into the observation group and control group (n=48 cases per group). The control group was administered the treatment of Lucentis intravitreal injection alone and the observation group was administered Lucentis combined with PDT. The therapeutic effects were compared. The best corrected visual acuity of patients in the two groups increased gradually after treatment. Patients in the observation group had a significantly higher visual acuity when compared to the control group 1 and 6 months post-operation. The differences were statistically significant (P<0.05). The proportion of patients with vision improvement in the observation group was higher than that in the control group from 1 to 6 months; differences were statistically significant (P<0.05). Through detection by color Doppler ultrasound within 6 months after treatment, we observed that the peak systolic velocity and arterial end diastolic velocity of retrobulbar optic nerve bitemporal PCA of the observation group were higher than those of the control group. The values of arterial resistance index and pulsatility index of the observation group were lower than those of control group. The differences were statistically significant (P<0.05). Six months after treatment, the value of central foveal thickness of the observation group was lower than that of the control group, the value of mean sensitivity of visual field parameter 10° and 4° was higher in the observation group than in the control group, and the absolute value of mean defects in the observation group were lower than that of the control group. In summary, the differences were statistically significant (P<0.05). Anti-VEGF drugs combined with PDT can optimize the overall vision of patients

  14. Novel Endogenous Retrovirus in Rabbits Previously Reported as Human Retrovirus 5

    PubMed Central

    Griffiths, David J.; Voisset, Cécile; Venables, Patrick J. W.; Weiss, Robin A.

    2002-01-01

    Human retrovirus 5 (HRV-5) represented a fragment of a novel retrovirus sequence identified in human RNA and DNA preparations. In this study, the genome of HRV-5 was cloned and sequenced and integration sites were analyzed. Using PCR and Southern hybridization, we showed that HRV-5 is not integrated into human DNA. A survey of other species revealed that HRV-5 is present in the genomic DNA of the European rabbit (Oryctolagus cuniculus) and belongs to an endogenous retrovirus family found in rabbits. The presence of rabbit sequences flanking HRV-5 proviruses in human DNA extracts suggested that rabbit DNA was present in our human extracts, and this was confirmed by PCR analysis that revealed the presence of rabbit mitochondrial DNA sequences in four of five human DNA preparations tested. The origin of the rabbit DNA and HRV-5 in human DNA preparations remains unclear, but laboratory contamination cannot explain the preferential detection of HRV-5 in inflammatory diseases and lymphomas reported previously. This is the first description of a retrovirus genome in rabbits, and sequence analysis shows that it is related to but distinct from A-type retroelements of mice and other rodents. The species distribution of HRV-5 is restricted to rabbits; other species, including other members of the order Lagomorpha, do not contain this sequence. Analysis of HRV-5 expression by Northern hybridization and reverse transcriptase PCR indicates that the virus is transcribed at a low level in many rabbit tissues. In light of these findings we propose that the sequence previously designated HRV-5 should now be denoted RERV-H (for rabbit endogenous retrovirus H). PMID:12072509

  15. Rabbit and human hepatitis E virus strains belong to a single serotype.

    PubMed

    Wang, Song; Cheng, Xianfeng; Dai, Xing; Dong, Chen; Xu, Mingjie; Liang, Jiuhong; Dong, Min; Purdy, Michael A; Meng, Jihong

    2013-09-01

    Hepatitis E virus (HEV) is a zoonotic pathogen and all four established genotypes of HEV belong to a single serotype. The recently identified rabbit HEV is antigenically and genetically related to human HEV. It is unclear whether rabbit HEV belongs to the same serotype as human HEV. The purpose of this study was to determine the serotypic relationship between rabbit and human HEVs. HEV ORF2 recombinant capsid protein p166 (amino acids 452-617) of four known HEV genotypes and rabbit HEV were used to induce immune serum, which were evaluated for their ability to neutralize human HEV genotype 1, 4, and rabbit HEV strains by an in vitro PCR-based HEV neutralization assay. Immune sera of five kinds of p166 proteins were all found to neutralize or cross-neutralize the three different HEV strains, suggesting a common neutralization epitope(s) existing between human and rabbit HEV. Rabbit models of a second-passage rabbit HEV strain, JS204-2, and a genotype 4 human HEV strain, NJ703, were established as evidenced by fecal virus shedding, viremia and anti-HEV IgG seroconversion. Six rabbits, recovered from JS204 infection, were challenged with NJ703, and another six recovered from NJ703 infection were challenged with JS204-2. After challenge, viremia was not detected, shorter fecal virus shedding durations and obvious early stage declines in anti-HEV IgG values were observed. The results from this study indicate that rabbit HEV belongs to the same serotype as human HEV.

  16. Preclinical aspects of anti-VEGF agents for the treatment of wet AMD: ranibizumab and bevacizumab.

    PubMed

    Meyer, C H; Holz, F G

    2011-06-01

    Three anti-vascular endothelial growth factor (VEGF) therapies are currently used for the treatment of patients with wet age-related macular degeneration (AMD): pegaptanib, ranibizumab, and bevacizumab. Ranibizumab is an antibody fragment approved for the treatment of wet AMD. Bevacizumab is a full-length antibody registered for use in oncology but unlicensed for wet AMD. However, it is used off-label worldwide not only for wet AMD but also for various other ocular diseases associated with macular edema and abnormal vessel growth. We consider aspects of ranibizumab and bevacizumab in relation to their molecular characteristics, in vitro and in vivo properties, and preclinical safety data. Before 2009, most studies described the short-term toxicity of bevacizumab in multiple cell types of the eye. Since 2009, an increasing number of studies have compared the properties of ranibizumab and bevacizumab and investigated their impact on retinal cell functioning. Compared with bevacizumab, ranibizumab neutralizes VEGF better at low concentrations, maintains efficacy for longer, and has a higher retinal penetration and potency. Studies in animals demonstrate ranibizumab to be better localized to the injected eye, whereas bevacizumab appears to have a greater effect in the fellow eye. In humans, a localized and systemic effect has been reported for both molecules. In conclusion, overlapping yet distinct pharmacological properties of ranibizumab and bevacizumab indicate that safety or efficacy data from one cannot be extrapolated to the other.

  17. Outcomes of 23-Gauge Vitrectomy Combined with Phacoemulsification, Panretinal Photocoagulation, and Trabeculectomy without Use of Anti-VEGF Agents for Neovascular Glaucoma with Vitreous Hemorrhage

    PubMed Central

    Yan, Hua

    2016-01-01

    Purpose. To evaluate the outcomes of 23-gauge vitrectomy combined with phacoemulsification, PRP and trabeculectomy without use of anti-VEGF-agents for NVG. Methods. Eighteen eyes of 18 patients with NVG underwent 23-gauge vitrectomy combined with phacoemulsification, PRP and trabeculectomy without use of anti-VEGF agents. The preoperative BCVA ranged from light perception to 0.2. The preoperative IOP ranged from 38 mmHg to 64 mmHg with a mean of 54 ± 8 mmHg. The average follow-up time was 14.5 ± 3 months with a range from 11 to 24 months. Results. The postoperative VA increased in 14 eyes and was stable in 4 eyes at the final follow-up. The mean IOP was 12 ± 3 mmHg at postoperative day 1. The mean IOP was 15 ± 2 mmHg, 16 ± 3 mmHg, 23 ± 5 mmHg, 28 ± 4 mmHg, 22 ± 5 mmHg, 17 ± 3 mmHg, and 19 ± 4 mmHg at postoperative days 2 and 3, 1, 2, 3, and 12 weeks, and 1 year postoperatively, respectively, with a range from 10 to 30 mmHg at the final follow-up time point of one year. The IOP was significantly lower than the preoperative one 12 weeks postoperatively (p < 0.05). Conclusion. 23-gauge vitrectomy combined with phacoemulsification, PRP, and trabeculectomy without use of anti-VEGF-agents is a safe and effective method in treating NVG. PMID:26885379

  18. Effect of anti-VEGF drugs combined with photodynamic therapy in the treatment of age-related macular degeneration

    PubMed Central

    Dong, Yi; Wan, Guangming; Yan, Panshi; Chen, Yue; Wang, Wenzhan; Peng, Guanghua

    2016-01-01

    We analyzed the effects of anti-vascular endothelial growth factor (VEGF) drugs combined with photodynamic therapy (PDT) in the treatment of age-related macular degeneration (AMD). Ninety-six cases (192 eyes) of AMD were included in this study and randomly divided into the observation group and control group (n=48 cases per group). The control group was administered the treatment of Lucentis intravitreal injection alone and the observation group was administered Lucentis combined with PDT. The therapeutic effects were compared. The best corrected visual acuity of patients in the two groups increased gradually after treatment. Patients in the observation group had a significantly higher visual acuity when compared to the control group 1 and 6 months post-operation. The differences were statistically significant (P<0.05). The proportion of patients with vision improvement in the observation group was higher than that in the control group from 1 to 6 months; differences were statistically significant (P<0.05). Through detection by color Doppler ultrasound within 6 months after treatment, we observed that the peak systolic velocity and arterial end diastolic velocity of retrobulbar optic nerve bitemporal PCA of the observation group were higher than those of the control group. The values of arterial resistance index and pulsatility index of the observation group were lower than those of control group. The differences were statistically significant (P<0.05). Six months after treatment, the value of central foveal thickness of the observation group was lower than that of the control group, the value of mean sensitivity of visual field parameter 10° and 4° was higher in the observation group than in the control group, and the absolute value of mean defects in the observation group were lower than that of the control group. In summary, the differences were statistically significant (P<0.05). Anti-VEGF drugs combined with PDT can optimize the overall vision of patients

  19. [Comparison of photodynamic effect with respect to human and rabbit erythrocytes].

    PubMed

    Galebskaia, L V; Solovtsova, I L; Solov'eva, M A; Zammoeva, D B; Kuz'menkov, A N

    2011-01-01

    Parameters of photoinduced lysis are studied for human and rabbit erythrocytes (photosensibilizer--Radachlorin, the light source--Shuttle HeNe lazer, lambda = 633 nm). The higher sensitivity to irradiation is revealed for rabbit erythrocytes. Treatment of erythrocytes with trypsin showed the surface proteins in human cells to produce a protective effect. Trypsynization of rabbit erythrocytes produced the opposite action--the rate of photohemolysis increased. Results of the study indicate the differences in sensitivity to the photoinduced lysis of erythrocytes of different species and participation of erythrocytes proteins in the effect of photohemolysis.

  20. Long-term results of combination therapy using anti-VEGF agents and dexamethasone intravitreal implant for retinal vein occlusion: an investigational case series

    PubMed Central

    Singer, Michael A; Jansen, Michael E; Tyler, Lyndon; Woods, Paul; Ansari, Faisal; Jain, Udit; Singer, Joshua; Bell, Darren; Krambeer, Chelsey

    2017-01-01

    Background One limitation of anti-VEGF therapy is the need for monthly retreatment to maintain efficacy. The purpose of this study was to determine the duration of effect in eyes with macular edema (ME) secondary to branch or central retinal vein occlusion (BRVO or CRVO) treated with anti-VEGF therapy plus sustained-release dexamethasone (DEX implant; Ozurdex). Materials and methods This open-label, interventional case series included 62 eyes with ME due to RVO, central foveal thickness (CFT) >300 μm, and best-corrected visual acuity (BCVA) of 20/40 or worse. Each treatment cycle included an anti-VEGF injection followed 2 weeks later with DEX implant. Patients were eligible for retreatment if CFT increased to >290 μm or increased by >50 μm from the lowest measurement, or if BCVA decreased by six or more Snellen letters. Efficacy and safety were evaluated 2 and 4–6 weeks after the beginning of each treatment cycle and every 4 weeks thereafter until retreatment criteria were met. The primary outcome measure was time to retreatment. Secondary outcome measures included BCVA, CFT, and safety parameters. Results The mean reinjection interval for all patients was 135.5±36.4 days. There was no statistically significant difference in mean intertreatment interval for up to six cycles of treatment or between eyes with BRVO or CRVO (P≥0.058). Mean peak change in BCVA was 13.8 letters, and 47.6% of eyes gained three or more lines of BCVA. The mean peak decrease in CFT across all treatment cycles was 200.9 μm for eyes with BRVO and 219.2 μm for eyes with CRVO. The percentage of patients with CFT ≤300 μm at any time during a given treatment cycle ranged from 78% to 94% among eyes with BRVO and from 85% to 100% among eyes with CRVO. Intraocular pressure increased in 19 of 62 eyes, and 26 of 44 phakic eyes underwent cataract surgery. Conclusion In eyes with ME due to RVO, treatment with an anti-VEGF agent plus DEX implant provided a predictable duration of effect, as

  1. Subretinal recombinant tissue plasminogen activator and pneumatic displacement for the management of subretinal hemorrhage occurring after anti-VEGF injections for wet AMD.

    PubMed

    Tognetto, Daniele; Skiadaresi, Eirini; Cecchini, Paolo; Ravalico, Giuseppe

    2011-01-01

    We describe three cases of submacular hemorrhage that occurred two to four days after anti-VEGF intravitreal injection for occult choroidal neovascularisation in age-related macular degeneration and their management with 25 gauge pars plana vitrectomy with injection of subretinal recombinant tissue plasminogen activator (rTPA) followed by fluid-air exchange and postoperative prone position. Vitrectomy, subretinal rTPA injection and fluid-gas exchange apply as a safe and effective treatment in these cases. Functional results seem to be positive especially if surgical treatment is promptly performed.

  2. How Does Domain Replacement Affect Fibril Formation of the Rabbit/Human Prion Proteins

    PubMed Central

    Yan, Xu; Huang, Jun-Jie; Zhou, Zheng; Chen, Jie; Liang, Yi

    2014-01-01

    Background It is known that in vivo human prion protein (PrP) have the tendency to form fibril deposits and are associated with infectious fatal prion diseases, while the rabbit PrP does not readily form fibrils and is unlikely to cause prion diseases. Although we have previously demonstrated that amyloid fibrils formed by the rabbit PrP and the human PrP have different secondary structures and macromolecular crowding has different effects on fibril formation of the rabbit/human PrPs, we do not know which domains of PrPs cause such differences. In this study, we have constructed two PrP chimeras, rabbit chimera and human chimera, and investigated how domain replacement affects fibril formation of the rabbit/human PrPs. Methodology/Principal Findings As revealed by thioflavin T binding assays and Sarkosyl-soluble SDS-PAGE, the presence of a strong crowding agent dramatically promotes fibril formation of both chimeras. As evidenced by circular dichroism, Fourier transform infrared spectroscopy, and proteinase K digestion assays, amyloid fibrils formed by human chimera have secondary structures and proteinase K-resistant features similar to those formed by the human PrP. However, amyloid fibrils formed by rabbit chimera have proteinase K-resistant features and secondary structures in crowded physiological environments different from those formed by the rabbit PrP, and secondary structures in dilute solutions similar to the rabbit PrP. The results from transmission electron microscopy show that macromolecular crowding caused human chimera but not rabbit chimera to form short fibrils and non-fibrillar particles. Conclusions/Significance We demonstrate for the first time that the domains beyond PrP-H2H3 (β-strand 1, α-helix 1, and β-strand 2) have a remarkable effect on fibrillization of the rabbit PrP but almost no effect on the human PrP. Our findings can help to explain why amyloid fibrils formed by the rabbit PrP and the human PrP have different secondary

  3. Rabbit medicine.

    PubMed

    Jordan, Dinah G

    2007-01-01

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

  4. Rabbit Model of Human Gliomas: Implications for Intra-Arterial Drug Delivery

    PubMed Central

    Qin, Huamin; Janowski, Miroslaw; Pearl, Monica S.; Malysz-Cymborska, Izabela; Li, Shen; Eberhart, Charles G.

    2017-01-01

    The prognosis for malignant brain tumors remains poor despite a combination of surgery, radiotherapy, and chemotherapy. This is partly due to the blood-brain barrier, a major obstacle that prevents therapeutic agents from effectively reaching the tumor. We have recently developed a method for precise and predictable opening of the blood-brain barrier via the intra-arterial administration of mannitol, a hyperosmolar agent, in a rabbit model, whose vascular anatomy facilitates the use of standard interventional neuroradiology techniques and devices. To date, however, no protocols are available that enable human glioma modeling in rabbits. In this article, we report on the xenotransplantation of a human glioblastoma (GBM-1) in adult New Zealand rabbits. We induced multi-drug immunosuppression (Mycophenolate Mofetil, Dexamethasone, Tacrolimus) and stereotactically implanted GBM-1 tumor cells into rabbit brains. The rabbits were followed for 42 days, monitored by MRI and body weight measurements, and underwent postmortem histopathological analysis. On MRI, brain tumors were identified on T2-weighted scans. On histopathology, tumors were detected with hematoxylin/eosin and their human origin was confirmed with immunohistochemistry against human-specific antigens. Our method for human glioma modeling in rabbits provides the foundation to test novel treatment strategies, including intra-arterial therapeutic agent delivery. PMID:28103265

  5. Short-term Efficacy of Intravitreal Dexamethasone Implant in Vitrectomized Eyes with Recalcitrant Diabetic Macular Edema and Prior Anti-VEGF Therapy

    PubMed Central

    Shah, Ankoor R.; Xi, Mengqiao; Abbey, Ashkan M.; Yonekawa, Yoshihiro; Faia, Lisa J.; Hassan, Tarek S.; Ruby, Alan J.; Wolfe, Jeremy D.

    2016-01-01

    Purpose: To determine the efficacy of an intravitreal dexamethasone implant (IDI) for diabetic macular edema (DME) in vitrectomized eyes. Methods: This interventional retrospective consecutive case series included vitrectomized eyes undergoing IDI placement for treatment of recalcitrant DME between June 2011 and June 2014. All patients had previously received anti-VEGF therapy (ranibizumab or bevacizumab). Primary endpoints were changes in visual acuity (VA) and central retinal thickness (CRT) from baseline values one month after device implantation. Secondary endpoints were VA and CRT changes at 3 months. Results: A total of 8 eyes of 8 patients met the inclusion criteria. One month after IDI placement, there was a significant (p = 0.01) improvement in VA from 0.79 ± 0.52 logMAR (20/123 Snellen equivalent) to 0.64 ± 0.55 logMAR (20/88), meanwhile CRT improved from 455.75 ± 123.19 to 295.00 ± 90.39 μm (p = 0.02). These findings persisted at 3 months. Conclusion: In vitrectomized eyes previously treated with anti-VEGF agents for recalcitrant DME, implantation of the IDI appears to be efficacious in improving VA and CRT at 1-month with the observed benefits persisting for at least for 3 months. PMID:27413499

  6. Syphilis superinfection activates expression of human immunodeficiency virus I in latently infected rabbits.

    PubMed Central

    Tseng, C. K.; Hughes, M. A.; Hsu, P. L.; Mahoney, S.; Duvic, M.; Sell, S.

    1991-01-01

    Superinfection of latently human immunodeficiency virus (HIV)-infected rabbits with either Treponema pallidum or Shope fibroma virus (SFV) activates HIV expression. In addition, HIV-infected rabbits demonstrate prolonged cutaneous lesions (chancres) after intracutaneous challenge with T. pallidum, the causative agent of syphilis. Rabbits were infected by intravenous inoculation of 3 x 10(7) human T-cell lymphotrophic virus type III (HTLV-III)/B10 (HIV-1)-infected H9 (human) cells. Five weeks after initial infection, integrated HIV-1-specific DNA sequences were detected in the DNA of the peripheral blood lymphocytes of only one of eight rabbits using polymerase chain reactions (PCR); human DNA could not be detected at this time. Furthermore HIV infection could not be demonstrated by either seroconversion or PCR during the next 6 months. All HIV-infected rabbits remained clinically healthy and had normal white blood cell counts. Six months after HIV infection, four HIV-infected and two noninfected controls were superinfected with 10(6) T. pallidum in eight skin sites in the shaved skin of the back, and four infected and two control animals were challenged with an intradermal injection with SFV. After infection with either syphilis or SFV, the DNA from the white blood cells of all eight HIV-infected rabbits contained HIV sequences, and HIV sequences were demonstrated in dermal mononuclear cells of the syphilitic lesions by in situ hybridization. The SFV-induced tumors were rejected normally in the HIV-infected rabbits, but four of the four rabbits challenged with T. pallidum had delayed development of cutaneous lesions and three of four demonstrated larger and more prolonged lesions. White blood counts, mitogen responses, and interleukin-2 production remained within normal limits, and seroconversion for HIV was not detected. Three of four rabbits in a second group, challenged with T. pallidum 4 months after HIV-inoculation, also had delayed healing of syphilitic

  7. Rabbit muscle creatine phosphokinase. CDNA cloning, primary structure and detection of human homologues.

    PubMed

    Putney, S; Herlihy, W; Royal, N; Pang, H; Aposhian, H V; Pickering, L; Belagaje, R; Biemann, K; Page, D; Kuby, S

    1984-12-10

    A cDNA library was constructed from rabbit muscle poly(A) RNA. Limited amino acid sequence information was obtained on rabbit muscle creatine phosphokinase and this was the basis for design and synthesis of two oligonucleotide probes complementary to a creatine kinase cDNA sequence which encodes a pentapeptide. Colony hybridizations with the probes and subsequent steps led to isolation of two clones, whose cDNA segments partially overlap and which together encode the entire protein. The primary structure was established from the sequence of two cDNA clones and from independently determined sequences of scattered portions of the polypeptide. The reactive cysteine has been located to position 282 within the 380 amino acid polypeptide. The rabbit cDNA hybridizes to digests of human chromosomal DNA. This reveals a restriction fragment length polymorphism associated with the human homologue(s) which hybridizes to the rabbit cDNA.

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

    PubMed

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

    1980-01-01

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

  9. OBSERVATIONS ON THE PRODUCTION OF PYROGENIC SUBSTANCES BY RABBIT AND HUMAN LEUCOCYTES

    PubMed Central

    Fessler, J. H.; Cooper, K. E.; Cranston, W. I.; Vollum, R. L.

    1961-01-01

    1. The mechanism of release of a pyrogen from leucocytes has been studied in cells obtained from sterile rabbit peritoneal exudates and from rabbit blood. Attempts were made to induce human leucocytes—from blood—to release a pyrogen. 2. Rabbit leucocytes, kept below 4°C., were not pyrogenic and did not release any pyrogen when disintegrated. Incubating such cells, in various media, at 37°C. led to the formation of a pyrogen which was heat-labile. The maximum yield was attained after 1½ hours' incubation. 3. The formation of rabbit leucocytic pyrogen was prevented by freezing and thawing the leucocytes, by heating them to 56°C. for half an hour before incubation, and by ageing them in the cold. 4. Nitrofurazone (5-nitro-2-furaldehyde semicarbazone) prevents the formation of leucocytic pyrogen when given by mouth to the cell-donor animals, or when added to leucocytes in intro. 5. Leucocytes from rabbit blood formed leucocytic pyrogen, on incubation in saline, and this formation was also inhibited by nitrofurazone. 6. No leucocytic pyrogen was released from human leucocytes subjected to mechanical, osmotic, or thermal damage, and it was not formed when the cells were incubated in saline. 7. The source of rabbit leucocytic pyrogen, the action of nitrofurazone on leucocytes, and the supposed role of leucocytic pyrogen in fever are discussed. PMID:13699218

  10. Early treatment of acute submacular haemorrhage secondary to wet AMD using intravitreal tissue plasminogen activator, C3F8, and an anti-VEGF agent.

    PubMed

    de Silva, S R; Bindra, M S

    2016-07-01

    PurposeAcute submacular haemorrhage secondary to wet age-related macular degeneration (AMD) has a poor prognosis for which there is currently no 'gold standard' treatment. We evaluated the efficacy of early treatment using intravitreal triple therapy of tissue plasminogen activator (tPA), expansile gas, and an anti-VEGF agent.MethodsThis retrospective case series included eight patients presenting with acute submacular haemorrhage involving the fovea. All patients received treatment with 50 μg (0.05 ml) tPA, 0.3 ml 100% perfluoropropane (C3F8), and an anti-VEGF agent (0.05 mg Ranibizumab or 1.25 mg Bevacizumab in 0.05 ml) administered via intravitreal injection. An anterior chamber paracentesis post injection or vitreous tap was performed before injection to prevent retinal vascular occlusion secondary to raised intra-ocular pressure. Outcomes assessed were visual acuity, change in macular morphology, and complications.ResultsPatients presented promptly with delay between symptom onset and clinic review being 1.9±0.6 days (mean±SD). Treatment was delivered quickly with interval from presentation to treatment being 1.1±1.2 days. Symptom onset to treatment was 3.0±1.0 days. Subfoveal haemorrhage was effectively displaced in all patients. LogMAR visual acuity improved from 1.67±0.47 at presentation to 0.63±0.33 at final follow-up (P<0.0001), a mean of 7.9±4.8 months after treatment. Central retinal thickness improved from 658.1±174.2 μm at presentation to 316.6±142.4 μm at final follow-up (P=0.0028).ConclusionsEarly treatment of submacular haemorrhage using intravitreal tPA, C3F8, and anti-VEGF was effective in significantly improving visual acuity in this series of patients who presented soon after symptom onset. Treatment was well tolerated in this group of elderly and potentially frail patients.

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

    PubMed Central

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

    2014-01-01

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

  12. Noninvasive imaging of the functional effects of anti-VEGF therapy on tumor cell extravasation and regional blood volume in an experimental brain metastasis model.

    PubMed

    JuanYin, Juan; Tracy, Kirsten; Zhang, Luhua; Munasinghe, Jeeva; Shapiro, Erik; Koretsky, Alan; Kelly, Kathleen

    2009-01-01

    Brain metastasis has become an increasing cause of morbidity and mortality in cancer patients as the treatment of systemic disease has improved. Brain metastases frequently are highly vascularized, a process driven primarily by VEGF. VEGF mediates numerous changes within the vasculature including endothelial cell retraction and increased permeability, vasodilation, and new vessel formation. Here we describe a xenograft brain metastasis model that mimics the critical steps of metastasis including tumor cell dissemination and vascular adhesion, tumor growth and tumor associated angiogenesis. Magnetic resonance (MR) imaging was used to evaluate two aspects of the functional response of brain metastasis to the anti-VEGF receptor therapeutic, AZD2171 (Cediranib, RECENTIN). MR tracking of individual cells demonstrated that cediranib did not impede tumor cell extravasation into the brain parenchyma despite evidence that anti-VEGF treatment decreases the permeability of the blood brain barrier. In a second assay, blood volume imaging using ultrasmall superparamagnetic iron oxide revealed that treatment of well-developed brain metastasis with cediranib for 7 days led to a heterogeneous response with respect to individual tumors. Overall, there was a significant average decrease in the tumor vascular bed volume. The majority of large tumors demonstrated substantially reduced central blood volumes relative to normal brain while retaining a rim of elevated blood volume at the tumor brain interface. Small tumors or occasional large tumors displayed a static response. Models and assays such as those described here will be important for designing mechanism-based approaches to the use of anti-angiogenesis therapies for the treatment of brain metastasis.

  13. Physician, patient, and caregiver experience of different wet age-related macular degeneration anti-VEGF treatment regimens in Japan: a qualitative assessment

    PubMed Central

    Iida, Tomohiro; Ishii, Keirei

    2016-01-01

    Purpose The purpose of this study was to monitor anti-vascular endothelial growth factor (anti-VEGF) treatment regimens for wet age-related macular degeneration (wAMD) in clinical practice and to determine how they impact the physician, patient, and caregiver treatment experience. Materials and methods This was a qualitative analysis based on semistructured interviews with 20 ophthalmologists who had practiced both pro re nata (PRN) and treat-and-extend (T&E) anti-VEGF regimens for wAMD. Interview questions were constructed to assess how the different regimens affected patient and caregiver experiences (in the opinion of the ophthalmologist) in addition to the ophthalmologist’s own experience. The interview included questions relating to 1) issues and benefits of PRN and T&E; 2) logistical and operational issues of introducing proactive therapy, especially T&E, to PRN practice; and 3) actions taken to handle the issues raised in 2). Results A total of 18 interview results were eligible for analysis. The study demonstrated that the benefits of T&E compared with PRN included decreased burden of patient consultations, decreased patient and caregiver emotional burden, and a sustained period of macular dryness. The issues associated with T&E were increased number of injections and financial burden from prolonged treatment duration. The ophthalmologists also experienced difficulty explaining the significance of proactive injections to patients. Countermeasures to operational issues experienced by ophthalmologists varied by practice. Conclusion Patients, caregivers, and the practicing ophthalmologists experienced benefits associated with a T&E regimen. However, in order to encourage better understanding of the T&E regimen, including its smooth implementation and significance for patients, a formal T&E treatment guideline providing standard practice should be considered. PMID:28008223

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

    SciTech Connect

    Kabilan, S.; Suffield, S. R.; Recknagle, K. P.; Jacob, R. E.; Einstein, D. R.; Kuprat, A. P.; Carson, J. P.; Colby, S. M.; Saunders, J. H.; Hines, S. A.; Teeguarden, J. G.; Straub, T. M.; Moe, M.; Taft, S. C.; Corley, R. A.

    2016-09-01

    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 breathing 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.

  15. Computational Fluid Dynamics Modeling of Bacillus anthracis Spore Deposition in Rabbit and Human Respiratory Airways

    SciTech Connect

    Kabilan, Senthil; Suffield, Sarah R.; Recknagle, Kurtis P.; Jacob, Rick E.; Einstein, Daniel R.; Kuprat, Andrew P.; Carson, James P.; Colby, Sean M.; Saunders, James H.; Hines, Stephanie; Teeguarden, Justin G.; Straub, Tim M.; Moe, M.; Taft, Sarah; Corley, Richard A.

    2016-09-30

    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. 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.

  16. Therapeutic efficiency of tissue-engineered human corneal endothelium transplants on rabbit primary corneal endotheliopathy.

    PubMed

    Fan, Ting-jun; Zhao, Jun; Hu, Xiu-zhong; Ma, Xi-ya; Zhang, Wen-bo; Yang, Chao-zhong

    2011-06-01

    To evaluate the therapeutic efficiency of tissue-engineered human corneal endothelia (TE-HCEs) on rabbit primary corneal endotheliopathy (PCEP), TE-HCEs reconstructed with monoclonal human corneal endothelial cells (mcHCECs) and modified denuded amniotic membranes (mdAMs) were transplanted into PCEP models of New Zealand white rabbits using penetrating keratoplasty. The TE-HCEs were examined using diverse techniques including slit-lamp biomicroscopy observation and pachymeter and tonometer measurements in vivo, and fluorescent microscopy, alizarin red staining, paraffin sectioning, scanning and transmission electron microscopy observations in vitro. The corneas of transplanted eyes maintained transparency for as long as 200 d without obvious edema or immune rejection. The corneal thickness of transplanted eyes decreased gradually after transplanting, reaching almost the thickness of normal eyes after 156 d, while the TE-HCE non-transplanted eyes were turbid and showed obvious corneal edema. The polygonal corneal endothelial cells in the transplanted area originated from the TE-HCE transplant. An intact monolayer corneal endothelium had been reconstructed with the morphology, cell density and structure similar to those of normal rabbit corneal endothelium. In conclusion, the transplanted TE-HCE can reconstruct the integrality of corneal endothelium and restore corneal transparency and thickness in PCEP rabbits. The TE-HCE functions normally as an endothelial barrier and pump and promises to be an equivalent of HCE for clinical therapy of human PCEP.

  17. A Rabbit Model of Acanthamoeba Keratitis That Better Reflects the Natural Human Infection.

    PubMed

    Feng, Xianmin; Zheng, Wenyu; Wang, Yuehua; Zhao, Donghai; Jiang, Xiaoming; Lv, Shijie

    2015-08-01

    Acanthamoeba species are ubiquitous, free-living protozoa that can invade the cornea and result in Acanthamoeba keratitis (AK), a painful progressive sight-threatening corneal disease. Disease progression in current animal models is too rapid to mimic AK in humans accurately. This study provides a novel method for establishing AK in rabbits and compared it with the conventional method with regard to pathogenesis and immune response in humans. The New Zealand white rabbits were randomly divided into two experimental groups (Groups A and B). Rabbits in the Group A (n = 14) received intrastromal injections of 1 × 10(4) /100 µL Acanthamoeba healyi trophozoites (conventional AK model). The Group B animals (n = 14) received microinjections of 1 × 10(4) /10 µL A. healyi trophozoites between the corneal epithelium and Bowman's layer, anterior to the corneal stroma (novel AK model). In addition, two rabbits were left untreated as normal controls. AK in the treated rabbits was evaluated clinically, histopathologically, and immunologically for 35 days. AK was successfully established in both the conventional and novel model groups. Compared with the Group A, AK in the Group B displayed an efficient immune response with less severe pathology. Moreover, the self-limiting but chronic nature of the infection in the Group B was strikingly similar to that of AK in humans. The novel animal model for AK described here more closely simulates the pathogenesis and immune response of Acanthamoeba corneal infection in humans than the animal models currently in use.

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

    PubMed Central

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

    2016-01-01

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

  19. Rabbit cardiomyopathy associated with a virus antigenically related to human coronavirus strain 229E.

    PubMed Central

    Small, J. D.; Aurelian, L.; Squire, R. A.; Strandberg, J. D.; Melby, E. C.; Turner, T. B.; Newman, B.

    1979-01-01

    A new disease of rabbits is described. Following an acute febrile course, animals die or recover by the 11th day postinoculation. The characteristic pathologic finding is multifocal myocardial degeneration and necrosis. The disease can be transmitted by various routes with tissue filtrates or with infectious sera diluted to 10(-6) and passed through 0.1 micron filters. Virus particles with morphologic features characteristic of a coronavirus are present in infectious but not in normal rabbit serums. The antigen(s) in the infectious serums cross-reacts with the 229E and the OC43 strains of human coronavirus. Antigen cross-reacting with the 229E virus is detectable by immunofluorescent staining in frozen sections of heart tissue from sick but not from healthy animals. Animals surviving infection seroconvert to coronavirus specificity, as demonstrated by the presence in convalescent serums of antibody capable of reacting with the 339E virus. Susceptibility to infection has not been demonstrated in mice, hamsters, or guinea pigs, and the virus was not adapted for growth in tissue culture. It is uncertain whether the agent is a natural pathogen of rabbits or a coronavirus contaminant from another species, possibly human. The name rabbit infectious cardiomyopathy is suggested for this disease. Images Figure 8 Figure 5 Figure 6 Figure 3 Figure 4 Figure 1 Figure 2 Figure 7 PMID:222151

  20. Characterization of cDNA clones encoding rabbit and human serum paraoxonase: The mature protein retains its signal sequence

    SciTech Connect

    Hassett, C.; Richter, R.J.; Humbert, R.; Omiecinski, C.J.; Furlong, C.E. ); Chapline, C.; Crabb, J.W. )

    1991-10-22

    Serum paraoxonase hydrolyzes the toxic metabolites of a variety of organophosphorus insecticides. High serum paraoxonase levels appear to protect against the neurotoxic effects of organophosphorus substrates of this enzyme. The amino acid sequence accounting for 42% of rabbit paraoxonase was determined. From these data, two oligonucleotide probes were synthesized and used to screen a rabbit liver cDNA library. Human paraoxonase clones were isolated from a liver cDNA library by using the rabbit cDNA as a hybridization probe. Inserts from three of the longest clones were sequenced, and one full-length clone contained an open reading frame encoding 355 amino acids, four less than the rabbit paraoxonase protein. Amino-terminal sequences derived from purified rabbit and human paraoxonase proteins suggested that the signal sequence is retained, with the exception of the initiator methionine residue. Characterization of the rabbit and human paraoxonase cDNA clones confirms that the signal sequences are not processed, except for the N-terminal methionine residue. The rabbit and human cDNA clones demonstrate striking nucleotide and deduced amino acid similarities (greater than 85%), suggesting an important metabolic role and constraints on the evolution of this protein.

  1. The effects of chemical modification on the antigenicity of human and rabbit immunoglobulin G.

    PubMed Central

    Hunneyball, I M; Stanworth, D R

    1976-01-01

    In order to characterize the precise structure within human and rabbit IgG molecules against which 'general' rheumatoid factors are directed, an immunochemical comparison has been made of the effects of the selective substitution of specific amino acid side-chains on various types of antigenicity exhibited by human and rabbit IgG. The epsilon-amino groups of lysine residues have been substituted by citraconylation and carbamylation; whilst tyrosine residues have been substituted by nitration with tetranitromethane. In this manner, evidence has been obtained which indicates that the autoantigenic determinants of human IgG are structurally distinct from species-specific ones and from certain Fc-located allotypic markers (Gm(a) and Gm(x)). It is also concluded that lysine residues are probably not involved in the site of IgG reactivity with 'general' rheumatoid factors, in contrast to tyrosine residues which appear to be implicated in the activity of human but not rabbit IgG. Images Figure 4 PMID:68918

  2. Human adipose-derived mesenchymal progenitor cells engraft into rabbit articular cartilage.

    PubMed

    Wang, Wen; He, Na; Feng, Chenchen; Liu, Victor; Zhang, Luyi; Wang, Fei; He, Jiaping; Zhu, Tengfang; Wang, Shuyang; Qiao, Weiwei; Li, Suke; Zhou, Guangdong; Zhang, Li; Dai, Chengxiang; Cao, Wei

    2015-05-27

    Mesenchymal stem cells (MSCs) are known to have the potential for articular cartilage regeneration, and are suggested for the treatment of osteoarthritis (OA). Here, we investigated whether intra-articular injection of xenogeneic human adipose-derived mesenchymal progenitor cells (haMPCs) promoted articular cartilage repair in rabbit OA model and engrafted into rabbit articular cartilage. The haMPCs were cultured in vitro, and phenotypes and differentiation characteristics of cells were evaluated. OA was induced surgically by anterior cruciate ligament transection (ACLT) and medical meniscectomy of knee joints. At six weeks following surgery, hyaluronic acid (HA) or haMPCs was injected into the knee joints, the contralateral knee served as normal control. All animals were sacrificed at the 16th week post-surgery. Assessments were carried out by macroscopic examination, hematoxylin/eosin (HE) and Safranin-O/Fast green stainings and immunohistochemistry. The data showed that haMPC treatment promoted cartilage repair. Signals of human mitochondrial can be directly detected in haMPC treated cartilage. The haMPCs expressed human leukocyte antigen I (HLA-I) but not HLA-II-DR in vivo. These results suggest that intra-articular injection of haMPCs promotes regeneration of articular cartilage in rabbit OA model, and support the notion that MPCs are transplantable between HLA-incompatible individuals.

  3. Unusual metabolic characteristics in skeletal muscles of transgenic rabbits for human lipoprotein lipase

    PubMed Central

    Gondret, Florence; Jadhao, Sanjay B; Damon, Marie; Herpin, Patrick; Viglietta, Céline; Houdebine, Louis-Marie; Hocquette, Jean-François

    2004-01-01

    Background The lipoprotein lipase (LPL) hydrolyses circulating triacylglycerol-rich lipoproteins. Thereby, LPL acts as a metabolic gate-keeper for fatty acids partitioning between adipose tissue for storage and skeletal muscle primarily for energy use. Transgenic mice that markedly over-express LPL exclusively in muscle, show increases not only in LPL activity, but also in oxidative enzyme activities and in number of mitochondria, together with an impaired glucose tolerance. However, the role of LPL in intracellular nutrient pathways remains uncertain. To examine differences in muscle nutrient uptake and fatty acid oxidative pattern, transgenic rabbits harboring a DNA fragment of the human LPL gene (hLPL) and their wild-type littermates were compared for two muscles of different metabolic type, and for perirenal fat. Results Analyses of skeletal muscles and adipose tissue showed the expression of the hLPL DNA fragment in tissues of the hLPL group only. Unexpectedly, the activity level of LPL in both tissues was similar in the two groups. Nevertheless, mitochondrial fatty acid oxidation rate, measured ex vivo using [1-14C]oleate as substrate, was lower in hLPL rabbits than in wild-type rabbits for the two muscles under study. Both insulin-sensitive glucose transporter GLUT4 and muscle fatty acid binding protein (H-FABP) contents were higher in hLPL rabbits than in wild-type littermates for the pure oxidative semimembranosus proprius muscle, but differences between groups did not reach significance when considering the fast-twitch glycolytic longissimus muscle. Variations in both glucose uptake potential, intra-cytoplasmic binding of fatty acids, and lipid oxidation rate observed in hLPL rabbits compared with their wild-type littermates, were not followed by any modifications in tissue lipid content, body fat, and plasma levels in energy-yielding metabolites. Conclusions Expression of intracellular binding proteins for both fatty acids and glucose, and their

  4. Creation of chimeric human/rabbit APOBEC1 with HIV-1 restriction and DNA mutation activities

    NASA Astrophysics Data System (ADS)

    Ikeda, Terumasa; Ong, Eugene Boon Beng; Watanabe, Nobumoto; Sakaguchi, Nobuo; Maeda, Kazuhiko; Koito, Atsushi

    2016-01-01

    APOBEC1 (A1) proteins from lagomorphs and rodents have deaminase-dependent restriction activity against HIV-1, whereas human A1 exerts a negligible effect. To investigate these differences in the restriction of HIV-1 by A1 proteins, a series of chimeric proteins combining rabbit and human A1s was constructed. Homology models of the A1s indicated that their activities derive from functional domains that likely act in tandem through a dimeric interface. The C-terminal region containing the leucine-rich motif and the dimerization domains of rabbit A1 is important for its anti-HIV-1 activity. The A1 chimeras with strong anti-HIV-1 activity were incorporated into virions more efficiently than those without anti-HIV-1 activity, and exhibited potent DNA-mutator activity. Therefore, the C-terminal region of rabbit A1 is involved in both its packaging into the HIV-1 virion and its deamination activity against both viral cDNA and genomic RNA. This study identifies the novel molecular mechanism underlying the target specificity of A1.

  5. Transgenic rabbits as bioreactors for the production of human growth hormone.

    PubMed

    Limonta, J M; Castro, F O; Martínez, R; Puentes, P; Ramos, B; Aguilar, A; Lleonart, R L; de la Fuente, J

    1995-05-15

    Gene farming is one of the most promising areas in modern biotechnology. To assay the potential usefulness of transgenic rabbits as bioreactors, one call embryos were microinjected with a chimeric gene comprising 5' sequences from mouse whey acidic protein gene (mWAP) linked to the human growth hormone (hGH) gene. Transgenic animals were obtained and the presence of the foreign protein was detected in the milk and serum of these animals at levels of up to 50 micrograms ml-1 and 0.6 ng ml-1, respectively. Founder transgenics were able to transmit the microinjected gene to the first filial generation in a Mendelian fashion. These results showed that transgenic rabbits could constitute a suitable system for the rapid production of recombinant proteins in the milk of lactating females.

  6. Sheep, rabbit and chicken antisera against a human VH fragment: reactivity with immunoglobulins and lymphocytes.

    PubMed Central

    Michaelsen, T E; Lea, T

    1982-01-01

    Antisera against a human VH fragment obtained from an IgG3, VH II, kappa protein (KUP) were raised in rabbits, sheep and chicken. The three types of anti-VH antisera reacted equally well with both intact immunoglobulin molecules and isolated heavy chains. The antisera did not detect any free heavy chain specific antigens by sensitive enzyme-linked immunosorbent assay (ELISA) tests although they reacted with some antigens which were more or less hidden on intact immunoglobulin molecules but well expressed on isolated heavy chains. The antisera reacted with more than 90% of IgG, IgA and IgM present in normal pooled serum. Experiments with T cells from normal peripheral blood indicated that the sheep and rabbit anti-VH antisera reacted with a 70,000 mol.wt T-cell surface antigen. Images Figure 1 Figure 2 PMID:6802746

  7. An eighteen-month follow-up study on the effects of Intravitreal Dexamethasone Implant in diabetic macular edema refractory to anti-VEGF therapy

    PubMed Central

    Pacella, Fernanda; Romano, Maria Rosaria; Turchetti, Paolo; Tarquini, Giovanna; Carnovale, Anna; Mollicone, Antonella; Mastromatteo, Alessandra; Pacella, Elena

    2016-01-01

    AIM To evaluate the long-term efficacy and safety of dexamethasone implants in subjects affected by diabetic macular edema (DME) resistant to anti-vascular endothelial growth factor (VEGF) therapy. METHODS Thirty-two DME patients were enrolled. A 700 microgram slow release Intravitreal Dexamethasone Implant (Ozurdex®) was placed in the vitreous cavity. All patients were followed for 18mo. Best-corrected visual acuity (BCVA) measured with Early Treatment Diabetic Retinopathy Study (ETDRS) and central macular thickness (CMT) exams were carried out at baseline (T0) and after 1 (T1), 3 (T3), 4 (T4), 6 (T6), 9 (T9), 12 (T12), 15 (T15), and 18mo (T18) post injection. RESULTS Repeated measures ANOVA showed an effect of treatment on ETDRS (P<0.0001). Post hoc analyses revealed that ETDRS values were significantly increased at T1, T3, T4, T9, and T15 (P<0.001) as compared to baseline value (T0). At T6, T12, and T18, ETDRS values were still statistically higher than baseline (P<0.001 vs T0). However, at these time points, we observed a trend to return to baseline conditions. ANOVA also showed an effect of treatment (P<0.0001). CMT decreased significantly at T1, T3, T4, T9, and T15 (P<0.001). At T6 (P<0.01), T12 and T18 (P<0.001) CMT was also significantly lower than T0 although a trend to return to the baseline conditions was also observed. CONCLUSION Our findings demonstrate that Intravitreal Dexamethasone Implant is a good option to improve BCVA and CMT in DME patients resistant to anti-VEGF therapy. Our data also show that the use of drugs administered directly into the vitreous allows achieving appropriate and long-lasting concentration at the site of disease without systemic side effects. PMID:27803859

  8. Docetaxel-loaded single-wall carbon nanohorns using anti-VEGF antibody as a targeting agent: characterization, in vitro and in vivo antitumor activity

    NASA Astrophysics Data System (ADS)

    Zhao, Qian; Li, Nannan; Shu, Chang; Li, Ruixin; Ma, Xiaona; Li, Xuequan; Wang, Ran; Zhong, Wenying

    2015-05-01

    A novel antitumor drug delivery system, docetaxel (DTX)-loaded oxidized single-wall carbon nanohorns (oxSWNHs) with anti-VEGF monoclonal antibody (mAb) as a target agent was constructed. DTX was absorbed onto the oxSWNHs via the physical adsorption or π-π interaction. DSPE-PEG-COOH was non-covalently wrapped to the hydrophobic surface of oxSWNHs to improve its water solubility and biocompatibility. The mAb was bonded to the PEG through amide bond. The DTX@oxSWNHs-PEG-mAb (DDS) exhibited suitable particle size (191.2 ± 2.1 nm), good particle size distribution (PDI: 0.196), and negative zeta potential (-24.3 ± 0.85 mV). These features enhanced permeability and retention (EPR) effect and reduced the drug molecule uptake by the reticuloendothelial system. The in vitro drug release followed non-Fickian diffusion ( n = 0.6857, R = 0.9924) with the cumulative release of DTX 59 ± 1.35 % at 72 h. Compared with free DTX, the DDS enhanced the cytotoxicity in MCF-7 cell lines in vitro efficiently (IC50: 2.96 ± 0.6 μg/ml), and provided higher antitumor efficacy (TGI: 69.88 %) in vivo. The histological analysis indicated that the DDS had no significant side effect. Therefore, the new DDS is promising to attain higher pharmaceutical efficacy and lower side effects than free DTX for cancer therapy. The research demonstrated that DTX@oxSWNHs-PEG-mAb might have promising biomedical applications for future cancer therapy.

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

    PubMed Central

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

    1992-01-01

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

  10. The three-dimensional microanatomy of the rabbit and human cornea. A chemical and mechanical microdissection-SEM approach

    PubMed Central

    OJEDA, JOSÉ L.; VENTOSA, JUAN A.; PIEDRA, SONSOLES

    2001-01-01

    The three-dimensional (3D) microanatomy of the cornea is the major determinant of its optical and mechanical properties. Scanning electron microscopy (SEM) is the most commonly used method to obtain information on the overall 3D microanatomy of organs. However, SEM has not been successful in revealing the 3D microanatomy of the cornea, because the interior of the cornea is too compact to be explored by the electron beam. In this study, the 3D organisation of the cells and extracellular materials of human and rabbit corneas was examined after exposure by HCl and NaOH digestion, and by microdissection by the adhesive tape method. In the cornea of both species, all epithelial cells exhibited microplicae regardless of their location. This raises doubts about the tear film-holding role assigned to the microplicae of the superficial cells. Human and rabbit corneas differed in the collagen fibre patterns of the epithelial basement membranes. The 3D organisation of the stromal lamellae was similar in both species. In humans and rabbits, the keratocytes showed similar 3D features. However, the surface of human keratocytes located near Descemet's membrane exhibited small fenestrations that were not present in the rabbit keratocytes. The pattern of keratocyte innervation by the stromal neural plexus and 3D keratocyte microanatomy confirms that keratocytes form a large intercommunicating network within the corneal stroma. Two morphologically discrete subpopulations of keratocytes located at different stromal levels were identified in both human and rabbit corneas, suggesting that keratocytes are not functionally homogeneous. In addition, the density of the stromal neural plexus appeared to be greater in rabbits than in humans. Clear differences between human and rabbit corneas were observed in the collagen arrangement in Descemet's membrane, which may reflect their different biomechanical requirements. PMID:11760887

  11. Interspecies differences in the metabolism of methotrexate: An insight into the active site differences between human and rabbit aldehyde oxidase.

    PubMed

    Choughule, Kanika V; Joswig-Jones, Carolyn A; Jones, Jeffrey P

    2015-08-01

    Several drug compounds have failed in clinical trials due to extensive biotransformation by aldehyde oxidase (AOX) (EC 1.2.3.1). One of the main reasons is the difficulty in scaling clearance for drugs metabolised by AOX, from preclinical species to human. Using methotrexate as a probe substrate, we evaluated AOX metabolism in liver cytosol from human and commonly used laboratory species namely guinea pig, monkey, rat and rabbit. We found that the metabolism of methotrexate in rabbit liver cytosol was several orders of magnitude higher than any of the other species tested. The results of protein quantitation revealed that the amount of AOX1 in human liver was similar to rabbit liver. To understand if the observed differences in activity were due to structural differences, we modelled rabbit AOX1 using the previously generated human AOX1 homology model. Molecular docking of methotrexate into the active site of the enzyme led to the identification of important residues that could potentially be involved in substrate binding and account for the observed differences. In order to study the impact of these residue changes on enzyme activity, we used site directed mutagenesis to construct mutant AOX1 cDNAs by substituting nucleotides of human AOX1 with relevant ones of rabbit AOX1. AOX1 mutant proteins were expressed in Escherichia coli. Differences in the kinetic properties of these mutants have been presented in this study.

  12. The use of rat, rabbit or human bone marrow derived cells for cytocompatibility evaluation of metallic elements.

    PubMed

    Tomás, H; Carvalho, G S; Fernandes, M H; Freire, A P; Abrantes, L M

    1997-04-01

    Rat, rabbit and human bone marrow cells were cultured according to the method previously reported for cells of rat origin [1] and were exposed, or not (control), to corrosion products of a Co-Cr orthopaedic alloy as well as to metal salts containing Co2+, Cr3+ and Cr6+. Cells were cultured for 21 days and analysed for the following biochemical parameters: intracellular MTT reduction (i.e. cell viability/proliferation), alkaline phosphatase (ALP) activity and protein production. Morphological observations included both histochemistry (detection of ALP-positive cells, calcium and phosphate deposits) and scanning electron microscopy (SEM). Control cultures of rat and rabbit cells showed higher proliferation rates than human cells at the start of culture, but they all reached similar values on day 21. Protein production was parallel to cell proliferation. In contrast, ALP activity of rat cultures was much stronger than rabbit or human cultures. All cell types were able to develop the osteogenic phenotype in vitro.Co-Cr extract caused inhibitory effects on cell viability, on ALP activity and, to a lower extent, on protein production of all rat, rabbit and human cell cultures. Compared to rat and rabbit cultures, human cultures were the most sensitive to metal ions exposure.

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

    PubMed Central

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

    1991-01-01

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

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

    PubMed

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

    2016-09-01

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

  15. Effect of chemical enhancers and iontophoresis on thiocolchicoside permeation across rabbit and human skin in vitro.

    PubMed

    Artusi, Mariella; Nicoli, Sara; Colombo, Paolo; Bettini, Ruggero; Sacchi, Antonia; Santi, Patrizia

    2004-10-01

    The aim of this work was to study the permeation of thiocolchicoside across the skin in vitro. The effect of the chemical enhancer lauric acid and the physical technique of iontophoresis was investigated. Permeation experiments were performed in vitro using rabbit ear skin as barrier. The effect of lauric acid at different concentrations (2% and 4%) and of the vehicle (water, ethanol, or ethanol/water) was investigated. The primary effect of lauric acid was on the partitioning parameter, whereas the diffusive parameter did not change significantly. When human epidermis was used, the permeation parameters were generally lower, although not significantly different from rabbit ear skin. The data obtained with full-thickness human skin indicate that, despite the hydrophilic nature of thiocolchicoside, the resistance to drug transport is not limited to the stratum corneum, but that the underlying dermal tissue can also contribute. Iontophoresis enhanced the flux of thiocolchicoside compared with the passive control. The mechanism by which iontophoresis enhanced thiocolchicoside transport across the skin was electroosmosis. The permeation of thiocolchicoside across the skin can be enhanced using chemical or physical penetration enhancers.

  16. Protection of rabbits against challenge with rabbit papillomaviruses by immunization with the N terminus of human papillomavirus type 16 minor capsid antigen L2.

    PubMed

    Gambhira, Ratish; Jagu, Subhashini; Karanam, Balasubramanyam; Gravitt, Patti E; Culp, Timothy D; Christensen, Neil D; Roden, Richard B S

    2007-11-01

    Current L1 virus-like particle (VLP) vaccines provide type-restricted protection against a small subset of the human papillomavirus (HPV) genotypes associated with cervical cancer, necessitating continued cytologic screening of vaccinees. Cervical cancer is most problematic in countries that lack the resources for screening or highly multivalent HPV VLP vaccines, suggesting the need for a low-cost, broadly protective vaccinogen. Here, N-terminal L2 polypeptides comprising residues 1 to 88 or 11 to 200 derived from HPV16, bovine papillomavirus type 1 (BPV1), or cottontail rabbit papillomavirus (CRPV) were produced in bacteria. Rabbits were immunized with these N-terminal L2 polypeptides and concurrently challenged with CRPV and rabbit oral papillomavirus (ROPV). Vaccination with either N-terminal L2 polypeptides of CRPV effectively protected rabbits from CRPV challenge but not from papillomas induced by cutaneous challenge with CRPV genomic DNA. Furthermore, papillomas induced by CRPV genomic DNA deficient for L2 expression grew at the same rate as those induced by wild-type CRPV genomic DNA, further suggesting that the L2 polypeptide vaccines lack therapeutic activity. Neutralizing serum antibody titers of >15 correlated with protection (P < 0.001), a finding consistent with neutralizing antibody-mediated protection. Surprisingly, a remarkable degree of protection against heterologous papillomavirus types was observed after vaccination with N-terminal L2 polypeptides. Notably, vaccination with HPV16 L2 11-200 protected against cutaneous and mucosal challenge with CRPV and ROPV, respectively, papillomaviruses that are evolutionarily divergent from HPV16. Further, vaccination with HPV16 L2 11-200 generates broadly cross-neutralizing serum antibody, suggesting the potential of L2 as a second-generation preventive HPV vaccine antigen.

  17. Complete genome analysis of a rabbit rotavirus causing gastroenteritis in a human infant.

    PubMed

    Bonica, Melisa Berenice; Zeller, Mark; Van Ranst, Marc; Matthijnssens, Jelle; Heylen, Elisabeth

    2015-02-17

    Group A rotaviruses (RVA) are responsible for causing infantile diarrhea both in humans and animals. The molecular characteristics of lapine RVA strains are only studied to a limited extent and so far G3P[14] and G3P[22] were found to be the most common G/P-genotypes. During the 2012-2013 rotavirus season in Belgium, a G3P[14] RVA strain was isolated from stool collected from a two-year-old boy. We investigated whether RVA/Human-wt/BEL/BE5028/2012/G3P[14] is completely of lapine origin or the result of reassortment event(s). Phylogenetic analyses of all gene segments revealed the following genotype constellation: G3-P[14]-I2-R2-C2-M3-A9-N2-T6-E5-H3 and indicated that BE5028 probably represents a rabbit to human interspecies transmission able to cause disease in a human child. Interestingly, BE5028 showed a close evolutionary relationship to RVA/Human-wt/BEL/B4106/2000/G3P[14], another lapine-like strain isolated in a Belgian child in 2000. The phylogenetic analysis of the NSP3 segment suggests the introduction of a bovine(-like) NSP3 into the lapine RVA population in the past 12 years. Sequence analysis of NSP5 revealed a head-to-tail partial duplication, combined with two short insertions and a deletion, indicative of the continuous circulation of this RVA lineage within the rabbit population.

  18. Dodecyl N,N-dimethylamino acetate and azone enhance drug penetration across human, snake, and rabbit skin.

    PubMed

    Hirvonen, J; Rytting, J H; Paronen, P; Urtti, A

    1991-07-01

    The effectiveness of the penetration enhancers, dodecyl N,N-dimethylamino acetate (DDAA) and Azone, on pretreated human epidermis for the permeation of model drugs, indomethacin, 5-fluorouracil, and propranolol-HCl, was studied in in vitro diffusion cells. Snakeskin (Elaphe obsoleta) and rabbit pinna skin were compared as possible models for human skin. The drug concentrations were analyzed by HPLC. With all skins and all model drugs, DDAA increased drug permeability at least as well as Azone, and in most cases it was a more effective permeation enhancer. The relative permeation improvements in human skin, snakeskin, and rabbit skin were 10- to 20-, 5- to 50-, and 20- to 120-fold, respectively. Tritiated water served as an indicator of skin condition. Its penetration in the skin samples was independent of the drugs used, and both penetration enhancers significantly increased the flux of tritiated water through all skins. Thus, DDAA and Azone significantly increased the permeation of lipophilic and hydrophilic model compounds. Rabbit pinna skin was a poor model for human skin in vitro, while snakeskin was much closer to human skin in terms of transdermal permeability. In most cases drug permeability decreased in the order rabbit much greater than human greater than or less than snake.

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

    PubMed Central

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

    2002-01-01

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

  20. A rabbit model for sublingual drug delivery: comparison with human pharmacokinetic studies of propranolol, verapamil and captopril.

    PubMed

    Dali, Manisha M; Moench, Paul A; Mathias, Neil R; Stetsko, Paul I; Heran, Christopher L; Smith, Ronald L

    2006-01-01

    A rabbit model for investigating sublingual drug absorption was established yielding results consistent with clinical data reported in the literature. Using propranolol as a model compound the effect of formulation and dosing variables was explored as a means to characterize the limiting parameters of this model. In addition, verapamil and captopril were selected as reference compounds to compare this model to sublingual absorption in humans. Rabbits were dosed sublingually and systemic absorption was measured over time. Sublingual absorption of propranolol was dependent on dosing solution pH and volume. Intra-oral spray device did not affect the overall exposure compared to instillation using a syringe. Despite species and dosing regimen differences the relative bioavailabilities of propranolol and verapamil were very similar in rabbits and humans. In contrast, captopril absorption from the sublingual cavity of rabbits was low and did not agree with that observed in man. Here we report a sublingual rabbit model of drug delivery and its potential utility in preclinical development of intra-oral dosage forms.

  1. The disposition of voriconazole in mouse, rat, rabbit, guinea pig, dog, and human.

    PubMed

    Roffey, S J; Cole, S; Comby, P; Gibson, D; Jezequel, S G; Nedderman, A N R; Smith, D A; Walker, D K; Wood, N

    2003-06-01

    Voriconazole is a new triazole antifungal agent with potent, wide-spectrum activity. Its pharmacokinetics and metabolism have been studied in mouse, rat, rabbit, dog, guinea pig, and humans after single and multiple administration by both oral and intravenous routes. Absorption of voriconazole is essentially complete in all species. The elimination of voriconazole is characterized by non-linear pharmacokinetics in all species. Consequently, pharmacokinetic parameters are dependent upon dose, and a superproportional increase in area under the curve is seen with increasing dose in rat and dog toxicology studies. Following multiple administration, there is a decrease in systemic exposure. This is most pronounced in mouse and rat, less so in dog, and not observed in guinea pig or rabbit. Repeat-dose toxicology studies in mouse, rat, and dog have demonstrated that induction of cytochrome P450 by voriconazole (autoinduction of metabolism) is responsible for the decreased exposure in these species. Autoinduction of metabolism is not observed in humans, and plasma steady-state concentrations remain constant with time. Voriconazole is extensively metabolized in all species. The major pathways in humans involve fluoropyrimidine N-oxidation, fluoropyrimidine hydroxylation, and methyl hydroxylation. Also, N-oxidation facilitates cleavage of the molecule, resulting in loss of the fluoropyrimidine moiety and subsequent conjugation with glucuronic acid. Major pathways are represented in animal species. The major circulating metabolite in rat, dog, and human is the N-oxide of voriconazole. It is not thought to contribute to efficacy since it is at least 100-fold less potent than voriconazole against fungal pathogens in vitro.

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

    PubMed Central

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

    1991-01-01

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

  3. Association of the polymorphism Y402H in the CFH gene with response to anti-VEGF treatment in age-related macular degeneration: a systematic review and meta-analysis.

    PubMed

    Hong, Nan; Shen, Ye; Yu, Chen-Ying; Wang, Shu-Qun; Tong, Jian-Ping

    2016-06-01

    To explore whether the complement factor H (CFH) polymorphism rs1061170/Y402H is associated with responsiveness to antivascular endothelial growth factor (VEGF) agents in age-related macular degeneration (AMD). We reviewed the English literature to examine the association between the polymorphism rs1061170/Y402H of the CFH gene and responsiveness to treatment with anti-VEGF drugs in AMD patients. A meta-analysis of eligible studies was also performed. Pooled odds ratios (ORs) and 95% CIs were estimated using Stata V.12.0. Statistical heterogeneity was measured using Q-statistic testing. Fourteen relevant studies including a total of 2963 AMD patients were eligible. In AMD patients without a treatment history, individuals carrying the rs1061170/Y402H TT genotype were more likely to achieve a better outcome (OR = 1.932, 95% CI = 1.125-3.317, p = 0.017) than those carrying the CC genotype. The polymorphism rs1061170/Y402H might be a genetic predictor of treatment response to anti-VEGF therapy in AMD patients. Further prospective research including a larger number of patients is needed to validate this finding.

  4. A comparative study of candidal invasion in rabbit tongue mucosal explants and reconstituted human oral epithelium.

    PubMed

    Jayatilake, J A M S; Samaranayake, Y H; Samaranayake, L P

    2008-06-01

    The purpose of this study is to compare the light and scanning electron microscopic (SEM) features of tissue invasion by three Candida species (C. albicans, C. tropicalis, and C. dubliniensis) in two different tissue culture models: rabbit tongue mucosal explants (RTME) and reconstituted human oral epithelium (RHOE). Tongue mucosal biopsies of healthy New Zealand rabbits were maintained in explant culture using a transwell system. RHOE was obtained from Skinethic Laboratory (Nice, France). RTME and RHOE were inoculated with C. albicans, C. tropicalis, and C. dubliniensis separately and incubated at 37 degrees C, 5% CO(2), and 100% humidity up to 48 h. Light microscopic and SEM examinations of uninfected (controls) and infected tissues were performed at 24 and 48 h. C. albicans produced characteristic hallmarks of pathological tissue invasion in both tissue models over a period of 48 h. Hyphae penetrated through epithelial cells and intercellular gaps latter resembling thigmotropism. SEM showed cavitations on the epithelial cell surfaces particularly pronounced at sites of hyphal invasion. Some hyphae on RTME showed several clusters of blastospores attached in regular arrangements resembling "appareil sporifere". C. tropicalis and C. dubliniensis produced few hyphae mainly on RTME but they did not penetrate either model. Our findings indicate that multiple host-fungal interactions such as cavitations, thigmotropism, and morphogenesis take place during candidal tissue invasion. RTME described here appears to be useful in investigations of such pathogenic processes of Candida active at the epithelial front.

  5. Effects of peptides cleaved from human fibrinogen by plasmin on rabbit kidney cells in culture

    SciTech Connect

    Stachurska, J.; Janik, M.; Kobus, M.; Luczak, M.; Szmigielski, S.; Roszkowski, M.; Gerdin, B.; Saldeen, T.; Kopec, M.

    1983-02-15

    Low molecular weight fibrinogen degradation products (LMW-FDP) containing a mixture of dialysable peptides cleaved from human fibrinogen by plasmin are cytotoxic to an established line of rabbit kidney cells and to primary cultures of rabbit kidney cells. The presence of LMW-FDP in a concentration of 50 micrograms/ml during the cell cultivation caused a considerable release of /sup 51/Cr from prelabelled cells and inhibited /sup 3/H-thymidine and /sup 86/Rb uptake. Among three isolated peptides of established primary structure only one, 6D: Ser-Gln-Leu-Gln-Lys-Val-Pro-Pro-Glu-Trp-Lys, induced a significant effect, i.e. it enhanced /sup 3/H-thymidine incorporation. Two others, 6A: Ala-Arg-Pro-Ala-Lys and 6E: Thr-Ser-Glu-Val-Lys, did not influence the examined parameters. Hence other components of LMW-FDP must be assumed to be responsible for the cytotoxic effect on kidney cell cultures.

  6. 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.

  7. Enzyme therapy for pompe disease with recombinant human alpha-glucosidase from rabbit milk.

    PubMed

    Van den Hout, J M; Reuser, A J; de Klerk, J B; Arts, W F; Smeitink, J A; Van der Ploeg, A T

    2001-04-01

    Pompe disease is a metabolic myopathy caused by deficiency of lysosomal acid alpha-glucosidase. In this report we review the first 36 weeks of a clinical study on the safety and efficacy of enzyme therapy aimed at correcting the deficiency. Four patients with infantile Pompe disease were enrolled. They received recombinant human alpha-glucosidase from transgenic rabbit milk. The product is generally well tolerated and reaches the primary target tissues. Normalization of alpha-glucosidase activity in skeletal muscle was obtained and degradation of PAS-positive material was seen in tissue sections. The clinical condition of all patients improved. The effect on heart was most significant, with an impressive reduction of the left ventricular mass index (LVMI). Motor function improved. The positive preliminary results stimulate continuation and extension of efforts towards the realization of enzyme therapy for Pompe disease.

  8. N-/O-glycosylation analysis of human FVIIa produced in the milk of transgenic rabbits.

    PubMed

    Chevreux, Guillaume; Faid, Valegh; Scohyers, Jean-Marc; Bihoreau, Nicolas

    2013-12-01

    Human coagulation factor VIIa is a glycoprotein that promotes haemostasis through activation of the coagulation cascade extrinsic pathway. Most haemophilia A/B patients with inhibitors are treated by injection of plasma-derived or recombinant FVIIa. The use of recombinant products raises questions about the ability of the host cell to produce efficiently post-translationally modified proteins. Glycosylation is especially critical considering that it can modulate protein safety and efficacy. The present paper reports the N-/O-glycosylation pattern of a new recombinant human factor VIIa expressed in the mammary glands of transgenic rabbits. Glycosylation was investigated by chromatography and advanced mass spectrometry techniques for glycan identification and quantitation. Mass spectrometry (MS)/MS analyses were performed to confirm the glycan structures as well as the position and branching of specific monosaccharides or substituents. The two N-glycosylation sites were found to be fully occupied mostly by mono- and bi-sialylated biantennary complex-type structures, the major form being A(2)G(2)S(1). Some oligomannose/hybrid structures were retrieved in lower abundance, the major ones being GlcNAcα1,O-phosphorylated at the C6-position of a Man residue (Man-6-(GlcNAcα1,O-)phosphate motif) as commonly observed on lysosomal proteins. No immunogenic glycotopes such as Galili (Galα1,3Gal) and HD antigens (N-glycolylneuraminic acid (NeuGc)) were detected. Concerning O-glycosylation, the product exhibited O-fucose and O-glucose-(xylose)(0, 1, 2) motifs as expected. The N-glycosylation consistency was also investigated by varying production parameters such as the period of lactation, the number of consecutive lactations and rabbit generations. Results show that the transgenesis technology is suitable for the long-term production of rhFVIIa with a reproducible glycosylation pattern.

  9. Culicidae (Diptera) selection of humans, chickens and rabbits in three different environments in the province of Chaco, Argentina

    PubMed Central

    Stein, Marina; Zalazar, Laura; Willener, Juana Alicia; Almeida, Francisco Ludueña; Almirón, Walter Ricardo

    2013-01-01

    Studies were conducted to determine the selection of humans, chickens and rabbits by Culicidae in three different environments in the province of Chaco, Argentina. Mosquitoes were collected fortnightly using cylindrical metal traps containing animal bait (chickens and rabbits). The mosquitoes were collected between June 2001-May 2002. During the same period and with the same frequency, mosquitoes biting the human operators of the traps were collected during the first 15 min of exposure within different time intervals: from 09:00 am-11:00 am, 01:00 pm-03:00 pm, 05:00 pm-07:00 pm and 09:00 pm-10:00 pm. A total of 19,430 mosquitoes of 49 species belonging to 10 genera were collected. Culex species mainly selected chicken bait and Wyeomyia species selected rabbit bait. Ochlerotatus and Psorophora species were more abundant in rabbit-baited traps. Anopheles triannulatus, Coquillettidia nigricans, Ochlerotatus scapularis, Mansonia titillans and Psorophora albigenu showed a strong attraction for human bait. The Anopheles, Coquillettidia, Culex and Mansonia species were more active between 05:00 pm-09:00 pm, while Ochlerotatus, Psorophora, Haemagogus and Wyeomyia were most active from 09:00 am-07:00 pm. This study provides additional information about the biology and ecology of arbovirus vectors in Chaco. PMID:23903970

  10. GWAS study using DNA pooling strategy identifies association of variant rs4910623 in OR52B4 gene with anti-VEGF treatment response in age-related macular degeneration

    PubMed Central

    Riaz, Moeen; Lorés-Motta, Laura; Richardson, Andrea J.; Lu, Yi; Montgomery, Grant; Omar, Amer; Koenekoop, Robert K.; Chen, John; Muether, Philipp; Altay, Lebriz; Schick, Tina; Fauser, Sascha; Smailhodzic, Dzenita; van Asten, Freekje; de Jong, Eiko K.; Hoyng, Carel B.; Burdon, Kathryn P.; MacGregor, Stuart; Guymer, Robyn H.; den Hollander, Anneke I.; Baird, Paul N.

    2016-01-01

    Pooled DNA based GWAS to determine genetic association of SNPs with visual acuity (VA) outcome in anti-vascular endothelial growth factor (anti-VEGF) treated neovascular age-related macular degeneration (nAMD) patients. We performed pooled DNA based GWAS on 285 anti-VEGF treated nAMD patients using high density Illumina 4.3 M array. Primary outcome was change in VA in Early Treatment Diabetic Retinopathy Study (ETDRS) letters after 6 months of anti-VEGF treatment (patients who lost ≥5 ETDRS letters classified as non-responders and all remaining classified as responders). GWAS analysis identified 44 SNPs of interest: 37 with strong evidence of association (p < 9 × 10−8), 2 in drug resistance genes (p < 5 × 10−6) and 5 nonsynonymous changes (p < 1 × 10−4). In the validation phase, individual genotyping of 44 variants showed three SNPs (rs4910623 p = 5.6 × 10−5, rs323085 p = 6.5 × 10−4 and rs10198937 p = 1.30 × 10−3) remained associated with VA response at 6 months. SNP rs4910623 also associated with treatment response at 3 months (p = 1.5 × 10−3). Replication of these three SNPs in 376 patients revealed association of rs4910623 with poor VA response after 3 and 6 months of treatment (p = 2.4 × 10−3 and p = 3.5 × 10−2, respectively). Meta-analysis of both cohorts (673 samples) confirmed association of rs4910623 with poor VA response after 3 months (p = 1.2 × 10−5) and 6 months (p = 9.3 × 10−6) of treatment in nAMD patients. PMID:27892514

  11. Demineralized dentin matrix combined with recombinant human bone morphogenetic protein-2 in rabbit calvarial defects

    PubMed Central

    2016-01-01

    Objectives The aim of this study was to compare the osteogenic effects of demineralized dentin matrix (DDM) combined with recombinant human bone morphogenetic protein-2 (rhBMP-2) in rabbit calvarial defects with DDM and anorganic bovine bone (ABB) combined with rhBMP-2. Materials and Methods Four round defects with 8-mm diameters were created in each rabbit calvaria. Each defect was treated with one of the following: 1) DDM, 2) ABB/rhBMP-2, or 3) DDM/rhBMP-2. The rhBMP-2 was combined with DDM and ABB according to a stepwise dry and dip lyophilizing protocol. Histological and microcomputed tomography (µCT) analyses were performed to measure the amount of bone formation and bone volume after 2- and 8-week healing intervals. Results Upon histological observation at two weeks, the DDM and ABB/rhBMP-2 groups showed osteoconductive bone formation, while the DDM/rhBMP-2 group showed osteoconductive and osteoinductive bone formation. New bone formation was higher in DDM/rhBMP-2, DDM and ABB decreasing order. The amounts of bone formation were very similar at two weeks; however, at eight weeks, the DDM/rhBMP-2 group showed a two-fold greater amount of bone formation compared to the DDM and ABB/rhBMP-2 groups. The µCT analysis showed markedly increased bone volume in the DDM/rhBMP-2 group at eight weeks compared with that of the DDM group. Notably, there was a slight decrease in bone volume in the ABB/rhBMP-2 group at eight weeks. There were no significant differences among the DDM, ABB/rhBMP-2, and DDM/rhBMP-2 groups at two or eight weeks. Conclusion Within the limitations of this study, DDM appears to be a suitable carrier for rhBMP-2 in orthotopic sites. PMID:27162749

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

    PubMed

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

    2014-01-01

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

  13. Inhibition of sphincter of Oddi function by the nitric oxide carrier S-nitroso-N-acetylcysteine in rabbits and humans.

    PubMed Central

    Slivka, A; Chuttani, R; Carr-Locke, D L; Kobzik, L; Bredt, D S; Loscalzo, J; Stamler, J S

    1994-01-01

    Nitric oxide (NO) is an inhibitor of gastrointestinal smooth muscle. Model systems of the gut predict the NO will complex with biological thiol (SH) groups, yielding S-nitrosothiols (RS-NO), which may limit the propensity to form mutagenic nitrosamines. The inhibitory effects of NO and its biologically relevant adducts on sphincter of Oddi (SO) motility have been inferred from animal studies; however, their importance in regulating human SO is not known. The objectives of this study were to (a) provide histologic confirmation of nitric oxide synthase (NOS) in human SO; (b) characterize the pharmacology of S-nitroso-N-acetylcysteine (SNAC), an exemplary S-nitrosothiol, on SO motility in a rabbit model; and (c) study the effects of topical SNAC on SO motility in humans. Immunocytochemical and histochemical identification of NOS was performed in human SO. The pharmacologic response of SNAC was defined in isolated rabbit SO using a standard bioassay. Topical SNAC was then applied to the duodenal papilla in patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) and biliary manometry. NOS was localized to nerve fibers and bundles of the SO in rabbits and humans. SNAC inhibited spontaneous motility (frequency and amplitude) as well as acetylcholine-induced elevations in SO basal pressure in the rabbit model. In patients undergoing ERCP and biliary manometry, topical SNAC inhibited SO contraction freqency, basal pressure, and duodenal motility. NOS is localized to neural elements in human SO, implicating a role for NO in regulating SO function. Supporting this concept, SNAC is an inhibitor of SO and duodenal motility when applied topically to humans during ERCP. Our data suggest a novel clinical approach using local NO donors to control gastrointestinal motility and regulate sphincteric function. Images PMID:7525649

  14. Cryptic Leishmaniosis by Leishmania infantum, a feature of canines only? A study of natural infection in wild rabbits, humans and dogs in southeastern Spain.

    PubMed

    Chitimia, L; Muñoz-García, C I; Sánchez-Velasco, D; Lizana, V; Del Río, L; Murcia, L; Fisa, R; Riera, C; Giménez-Font, P; Jiménez-Montalbán, P; Martínez-Ramírez, A; Meseguer-Meseguer, J M; García-Bacete, I; Sánchez-Isarria, M A; Sanchis-Monsonís, G; García-Martínez, J D; Vicente, V; Segovia, M; Berriatua, E

    2011-09-08

    An epidemiological study was carried out to investigate asymptomatic Leishmania infantum infection by PCR and ELISA in wild rabbits, humans and domestic dogs in southeastern Spain. Seroprevalence was 0% (0/36) in rabbits, 2% (13/657) in humans and 7% (14/208) in dogs. The prevalence of PCR-positives was 0.6% (1/162) in rabbits tested in a wide range of tissue samples, 2% (8/392) in humans analysed in blood samples and 10% (20/193) and 67% (29/43) in dogs analysed in blood and lymphoid tissue samples, respectively. Results suggest that wild rabbits have a very low risk of becoming chronically infected with L. infantum, and provide further evidence that cryptic L. infantum infection is widespread in the domestic dog population and is also present in a comparatively smaller proportion of healthy humans. The epidemiological and clinical implications of these findings are discussed.

  15. Development of the Lacrimal Apparatus in the Rabbit (Oryctolagus cuniculus) and Its Potential Role as an Animal Model for Humans

    PubMed Central

    Rehorek, S. J.; Holland, J. R.; Johnson, J. L.; Caprez, J. M.; Cray, J.; Mooney, M. P.; Hillenius, W. J.; Smith, T. D.

    2011-01-01

    Rabbits have been proposed as a model organism for the human lacrimal apparatus (LA), including the nasolacrimal duct (NLD), based principally on comparative studies of adult morphology; however, little is known about its development. The NLD first appears as an incomplete primordium in the subcutaneous region of the primordial eyelid and subsequently elongates to reach the naris. One posterior and three anterior orbital glands are present fetally although one of the anterior glands is soon lost. The NLD follows a tortuous path and passes through a bony canal consisting of lacrimal, maxilla, and maxilloturbinal bones at different regions. Although early developmental similarities exist to haplorhine primates, the narial opening of the NLD resembles strepsirrhines. This distinction, along with the ductal and glandular differences at the orbital end of the NLD, indicates that rabbits may be a poor model for LA drainage in primates, specifically humans. PMID:22567296

  16. Serological, biological, and molecular characterization of New Zealand white rabbits infected by intraperitoneal inoculation with cell-free human immunodeficiency virus.

    PubMed Central

    Reina, S; Markham, P; Gard, E; Rayed, F; Reitz, M; Gallo, R C; Varnier, O E

    1993-01-01

    The availability of a small laboratory animal model suitable for the evaluation of methods for prevention and treatment of human immunodeficiency virus type 1 infection would be a valuable resource for AIDS research. Here we describe the infection of a strain of domestic rabbits by intraperitoneal inoculation with cell-free human immunodeficiency virus type 1. Evidence of infection includes the presence of an immune response that has persisted for almost 3 years and the detection of an reisolation of infectious virus from peripheral blood mononuclear cells (PBMCs) and other tissues during the first 2 years. Typical viral proteins, DNA and RNA patterns, were observed in rabbit PBMCs and in cells infected by cocultivation with rabbit PBMCs. While a number of possible pathological changes were evaluated in infected rabbits, the presence of changes in lymph node structure similar to those reported in infected humans merits further investigation. Images PMID:7688823

  17. Volume regulatory potassium transport in rabbit and human sickle erythrocytes in vitro

    SciTech Connect

    Al-Rohil, N.S.

    1988-01-01

    One approach to the therapy of sickle cell anemia is to decrease the hemoglobin concentration by inducing a slight swelling of the cell to retard the rate of hemoglobin polymerization. We found that a prolonged incubation of rabbit or human SS red cell in hypotonic medium caused an inactivation of the inactivation of swelling-stimulated potassium transport. The inactivation may have important practical consequences for the therapy of sickle cell anemia. Large cytoskeleton-free vesicles were prepared in order to study the possible role of the spectrin-actin membrane skeleton in the swelling-stimulated and N-ethylmaleimide (NEM)-stimulated transport. NEM pretreatment stimulated {sup 86}Rb efflux in vesicles by a factor of 2.4 + 0.55 (mean {plus minus} S.D.). The NEM effect on {sup 86}Rb efflux was specific in that the {sup 22}Na efflux into a Na medium was not stimulated but actually inhibited. The {sup 86}Rb efflux from the vesicles was not stimulated by hypotonic media. This finding is consistent with a role of the membrane skeleton in the detection and/or transduction of the signal by which cell swelling activates the transport.

  18. Stretchable, multiplexed pH sensors with demonstrations on rabbit and human hearts undergoing ischemia.

    PubMed

    Chung, Hyun-Joong; Sulkin, Matthew S; Kim, Jong-Seon; Goudeseune, Camille; Chao, Hsin-Yun; Song, Joseph W; Yang, Sang Yoon; Hsu, Yung-Yu; Ghaffari, Roozbeh; Efimov, Igor R; Rogers, John A

    2014-01-01

    Stable pH is an established biomarker of health, relevant to all tissues of the body, including the heart. Clinical monitoring of pH in a practical manner, with high spatiotemporal resolution, is particularly difficult in organs such as the heart due to its soft mechanics, curvilinear geometry, heterogeneous surfaces, and continuous, complex rhythmic motion. The results presented here illustrate that advanced strategies in materials assembly and electrochemical growth can yield interconnected arrays of miniaturized IrOx pH sensors encapsulated in thin, low-modulus elastomers to yield conformal monitoring systems capable of noninvasive measurements on the surface of the beating heart. A thirty channel custom data acquisition system enables spatiotemporal pH mapping with a single potentiostat. In vitro testing reveals super-Nernstian sensitivity with excellent uniformity (69.9 ± 2.2 mV/pH), linear response to temperature (-1.6 mV °C(-1) ), and minimal influence of extracellular ions (<3.5 mV). Device examples include sensor arrays on balloon catheters and on skin-like stretchable membranes. Real-time measurement of pH on the surfaces of explanted rabbit hearts and a donated human heart during protocols of ischemia-reperfusion illustrate some of the capabilities. Envisioned applications range from devices for biological research, to surgical tools and long-term implants.

  19. Recombinant expression of human nerve growth factor beta in rabbit bone marrow mesenchymal stem cells.

    PubMed

    Fan, Bo-Sheng; Lou, Ji-Yu

    2010-12-01

    Nerve growth factor (NGF) is required for the differentiation and maintenance of sympathetic and sensory neurons. In the present study, the recombinant expression of human nerve growth factor beta (hNGF-β) gene in rabbit bone marrow mesenchymal stem cells (rMSCs) was undertaken. Recombinant vector containing hNGF-β was constructed and transferred into rMSCs, the expressions of the exogenous in rMSCs were determined by reverse transcriptase PCR (RT-PCR), ELISA and Western blot, whereas the biological activity of recombinant hNGF-β was confirmed using PC12 cells and cultures of dorsal root ganglion neurons from chicken embryos. The results showed that the hNGF-β gene expressed successfully in the rMSCs, a polypeptide with a molecular weight of 13.2 kDa was detected. The maximal expression level of recombinant hNGF-β in rMSCs reached 126.8012 pg/10(6) cells, the mean concentration was 96.4473 pg/10(6) cells. The recombinant hNGF-β in the rMSCs showed full biological activity when compared to commercial recombinant hNGF-β.

  20. Semisolid formulations containing cetirizine: human skin permeation and topical antihistaminic evaluation in a rabbit model.

    PubMed

    Ciurlizza, Claudia; Fernández, Francisco; Calpena, Ana Cristina; Lázaro, Raquel; Parra, Alexander; Clares, Beatriz

    2014-10-01

    Cetirizine dihydrochloride (CTZ) is a second-generation histamine H1 antagonist, effective for the treatment of a wide range of allergic diseases. It has been utilized for managing the symptoms of chronic urticaria and atopic skin conditions. Thus, two novel semisolid formulations, nanoemulsion (NE) and hydrogel (HG) were developed to study their potential utility as vehicles including cetirizine (CTZ) and evaluate the potential use as topical H1-antihistamines agents. The physicochemical and stability properties of both vehicles were tested. Drug release kinetics and human skin permeation studies were performed using Franz cells. The antihistaminic activity was assayed in New Zealand rabbits and compared with two commercial first generation antihistamines. Both formulations were stable and provided a sustained drug release. Amounts of CTZ remaining in the skin were higher for HG, showing the maximum biological effect at 30 min, similar to topical first generation H1-antihistamines commercially available. These results suggest that CTZ-HG could be a promising system for the treatment of topical allergy bringing rapid antihistaminic relief.

  1. Verapamil as an antiarrhythmic agent in congestive heart failure: hopping from rabbit to human?

    PubMed Central

    Stams, Thom RG; Bourgonje, Vincent JA; Vos, Marc A; van der Heyden, Marcel AG

    2012-01-01

    Repolarization-dependent cardiac arrhythmias only arise in hearts facing multiple ‘challenges’ affecting its so-called repolarization reserve. Congestive heart failure (CHF) is one such challenge frequently observed in humans and is accompanied by altered calcium handling within the contractile heart cell. This raises the question as to whether or not the well-known calcium channel antagonist verapamil acts as an antiarrhythmic drug in this setting, as seen in arrhythmia models without CHF. According to the study of Milberg et al. in this issue of BJP, the answer is yes. The results of this study, using a rabbit CHF model, raise important questions. First, given that the model combines CHF with a number of other interventions that predispose towards arrhythmia, will similar conclusions be reached in a setting where CHF is a more prominent proarrhythmic challenge; second, what is the extent to which other effects of calcium channel block would limit the clinical viability of this pharmacological approach in CHF? In vivo studies in large animal CHF models are now required to further explore this interesting, but complex, approach to the treatment of arrhythmia. LINKED ARTICLE This article is a commentary on Milberg et al., pp. 557–568 of this issue. To view this paper visit http://dx.doi.org/10.1111/j.1476-5381.2011.01721.x PMID:22188337

  2. Characterization of the rabbit homolog of human MUC1 glycoprotein isolated from bladder by affinity chromatography on immobilized jacalin.

    PubMed

    Higuchi, T; Xin, P; Buckley, M S; Erickson, D R; Bhavanandan, V P

    2000-07-01

    The urinary bladder is lined by transitional epithelium, the glycocalyx on the luminal surface has interesting properties and is implicated in protective functions. Glycoconjugates are major components of the glycocalyx, but their biochemical nature is not well understood. Previous studies on rabbit bladder indicated the presence of significant levels of sialoglycoproteins compared to glycosaminoglycans in the epithelium. In this study, rabbit explant cultures were radiolabeled by precursor sugars or amino acids and a major lectin-reactive glycoprotein of rabbit bladder mucosa was isolated by affinity chromatography on jacalin-agarose. The radiolabeled glycoprotein was purified to homogeneity by a second cycle on the lectin column, followed by gel filtration and density gradient centrifugation. The average molecular mass of the glycoprotein was estimated to be 245 kDa and 210 kDa by gel filtration and SDS-PAGE, respectively. Its buoyant density was 1.40 g/ml, suggesting a carbohydrate content of approximately 50%. The percent distribution of glucosamine-derived tritium label in sialic acid, galactosamine, and glucosamine was 30, 52, and 18, respectively. The glycoprotein consisted entirely of small sialylated and neutral oligosaccharides O-glycosidically linked to serine and threonine residues. The same glycoprotein could be immunoprecipitated with an antibody against the carboxy terminal 17 amino acid peptide of human MUC1 mucin glycoprotein. This suggests that this mucin glycoprotein is the rabbit homolog of MUC1 glycoprotein, which has been previously established to be a component of human bladder urothelium and has been purified from human urine and biochemically characterized.

  3. Human Bone Derived Collagen for the Development of an Artificial Corneal Endothelial Graft. In Vivo Results in a Rabbit Model

    PubMed Central

    Vázquez, Natalia; Chacón, Manuel; Rodríguez-Barrientos, Carlos A.; Merayo-Lloves, Jesús; Naveiras, Miguel; Baamonde, Begoña; Alfonso, Jose F.; Zambrano-Andazol, Iriana; Riestra, Ana C.; Meana, Álvaro

    2016-01-01

    Corneal keratoplasty (penetrating or lamellar) using cadaveric human tissue, is nowadays the main treatment for corneal endotelial dysfunctions. However, there is a worldwide shortage of donor corneas available for transplantation and about 53% of the world’s population have no access to corneal transplantation. Generating a complete cornea by tissue engineering is still a tough goal, but an endothelial lamellar graft might be an easier task. In this study, we developed a tissue engineered corneal endothelium by culturing human corneal endothelial cells on a human purified type I collagen membrane. Human corneal endothelial cells were cultured from corneal rims after corneal penetrating keratoplasty and type I collagen was isolated from remnant cancellous bone chips. Isolated type I collagen was analyzed by western blot, liquid chromatography -mass spectrometry and quantified using the exponentially modified protein abundance index. Later on, collagen solution was casted at room temperature obtaining an optically transparent and mechanically manageable membrane that supports the growth of human and rabbit corneal endothelial cells which expressed characteristic markers of corneal endothelium: zonula ocluddens-1 and Na+/K+ ATPase. To evaluate the therapeutic efficiency of our artificial endothelial grafts, human purified type I collagen membranes cultured with rabbit corneal endothelial cells were transplanted in New Zealand white rabbits that were kept under a minimal immunosuppression regimen. Transplanted corneas maintained transparency for as long as 6 weeks without obvious edema or immune rejection and maintaining the same endothelial markers that in a healthy cornea. In conclusion, it is possible to develop an artificial human corneal endothelial graft using remnant tissues that are not employed in transplant procedures. This artificial endothelial graft can restore the integrality of corneal endothelium in an experimental model of endothelial dysfunction

  4. Prostaglandin E1 inhibits collagenase gene expression in rabbit synoviocytes and human fibroblasts.

    PubMed

    Salvatori, R; Guidon, P T; Rapuano, B E; Bockman, R S

    1992-07-01

    Cartilage breakdown, as seen in inflammatory and degenerative joint diseases, can be mediated by proteolytic enzymes, such as the metalloproteinase collagenase, the only enzyme able to digest collagen at neutral pH. In vitro collagenase gene expression can be stimulated by the phorbol ester tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate. We have investigated the effect of prostaglandin E1 (PGE1) on 12-O-tetradecanoyl-phorbol-13-acetate-stimulated collagenase mRNA levels in the rabbit synoviocyte cell line HIG-82. PGE1, but not PGE2 or PGF2 alpha, was able to selectively reduce collagenase mRNA levels in a dose-dependent fashion. PGE1 markedly increased intracellular levels of cAMP, while PGE2 and PGF2 alpha had little or no effect on cAMP production in the HIG-82 synoviocytes. Agents known to increase intracellular cAMP levels, such as the adenyl cyclase activator forskolin and the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX), mimicked the effect of PGE1, on collagenase mRNA levels. PGE1, forskolin, and IBMX also decreased collagenase mRNA levels in human skin fibroblasts, demonstrating that this observation was not unique to the HIG-82 cell line. Transient transfection experiments carried out in HIG-82 cells using a 1.2-kilobase portion of the 5'-flanking region of the human collagenase gene linked to the reporter gene luciferase demonstrated that PGE1, forskolin, and IBMX exert their inhibitory effect on the promoter region of the collagenase gene.

  5. Acute Radiation Hypotension in the Rabbit: a Model for the Human Radiation Shock Syndrome.

    NASA Astrophysics Data System (ADS)

    Makale, Milan Theodore

    This study has shown that total body irradiation (TBI) of immature (40 to 100 day old) rabbits leads to an acute fall in mean arterial pressure (MAP) 30 to 90 minutes after exposure, which takes no more than about three minutes, and often results in pressures which are less than 50% of the lowest pre-exposure MAP. This is termed acute cardiovascular collapse (ACC). ACC is often accompanied by ECG T-wave elevation, a sharp rise in ear temperature, labored breathing, pupillary constriction, bladder emptying, and loss of abdominal muscle tone. About 73% of 40 to 100 day rabbits exhibit ACC; the others and most older rabbits display gradual pressure reductions (deliberate hypotension) which may be profound, and which may be accompanied by the same changes associated with ACC. ACC and deliberate hypotension occurred in rabbits cannulated in the dorsal aorta, and in non-operated animals. The decline in MAP for all 40 to 100 day cannulated rabbits (deliberate and ACC responders) is 55.4%. The experiments described below only involved 40 to 100 day cannulated TBI rabbits. Heart region irradiation resulted in an average MAP decline of 29.1%, with 1/15 rabbits showing ACC. Heart shielding during TBI reduced the decline in MAP to 19%, with 1/10 rabbits experiencing ACC. These results imply that the heart region, which includes the heart, part of the lungs, neural receptors, roots of the systemic vessels, and the blood, is a sensitive target. Bilateral vagotomy reduced the decline in MAP to 24.9%, and abolished ACC. Atropine (6 mg/kg) reduced the frequency of ACC to 26%, and the decline in MAP to 41.4%. In 11/13 rabbits the voltage generated by left vagal transmission rose after TBI. The vagi appear to participate in radiation hypotension. Heart shielding together with bilateral vagotomy reduced the decline in MAP to only 9.9%, with no ACC responders. The mean right ventricular pressure (MRVP) rose after TBI in 8/10 rabbits. In animals which displayed either ACC or steep

  6. Laying the Foundations for a Human-Predator Conflict Solution: Assessing the Impact of Bonelli's Eagle on Rabbits and Partridges

    PubMed Central

    Moleón, Marcos; Sánchez-Zapata, José A.; Gil-Sánchez, José M.; Barea-Azcón, José M.; Ballesteros-Duperón, Elena; Virgós, Emilio

    2011-01-01

    Background Predation may potentially lead to negative effects on both prey (directly via predators) and predators (indirectly via human persecution). Predation pressure studies are, therefore, of major interest in the fields of theoretical knowledge and conservation of prey or predator species, with wide ramifications and profound implications in human-wildlife conflicts. However, detailed works on this issue in highly valuable –in conservation terms– Mediterranean ecosystems are virtually absent. This paper explores the predator-hunting conflict by examining a paradigmatic, Mediterranean-wide (endangered) predator-two prey (small game) system. Methodology/Principal Findings We estimated the predation impact (‘kill rate’ and ‘predation rate’, i.e., number of prey and proportion of the prey population eaten, respectively) of Bonelli's eagle Aquila fasciata on rabbit Oryctolagus cuniculus and red-legged partridge Alectoris rufa populations in two seasons (the eagle's breeding and non-breeding periods, 100 days each) in SE Spain. The mean estimated kill rate by the seven eagle reproductive units in the study area was c. 304 rabbits and c. 262 partridges in the breeding season, and c. 237 rabbits and c. 121 partridges in the non-breeding period. This resulted in very low predation rates (range: 0.3–2.5%) for both prey and seasons. Conclusions/Significance The potential role of Bonelli's eagles as a limiting factor for rabbits and partridges at the population scale was very poor. The conflict between game profitability and conservation interest of either prey or predators is apparently very localised, and eagles, quarry species and game interests seem compatible in most of the study area. Currently, both the persecution and negative perception of Bonelli's eagle (the ‘partridge-eating eagle’ in Spanish) have a null theoretical basis in most of this area. PMID:21818399

  7. The flavonols quercetin, myricetin, kaempferol, and galangin inhibit the net oxygen consumption by immune complex-stimulated human and rabbit neutrophils.

    PubMed

    Figueiredo-Rinhel, Andréa S G; Santos, Everton O L; Kabeya, Luciana M; Azzolini, Ana Elisa C S; Simões-Ambrosio, Livia M C; Lucisano-Valim, Yara M

    2014-01-01

    Stimulated human neutrophils exhibit increased net oxygen consumption (NOC) due to the conversion of O2 into the superoxide anion by the NADPH oxidase enzymatic complex during the respiratory burst. In several inflammatory diseases, overproduction of these oxidants causes tissue damage. The present study aims to: (a) optimize the experimental conditions used to measure the NOC in serum-opsonized zymosan (OZ)- and insoluble immune complex (i-IC)-stimulated human and rabbit neutrophils; and (b) compare the effect of four flavonols (quercetin, myricetin, kaempferol, and galangin) on this activity. We used a Clark-type oxygen electrode to measure the NOC of stimulated neutrophils. Eliciting the neutrophil respiratory burst with OZ and i-IC yielded similar maximum O2 uptake levels within the same species, but the human neutrophil NOC was almost four times higher than the rabbit neutrophil NOC. The optimal experimental conditions established for both cell types were 4 x 10(6) neutrophils mL(-1), 2 mg mL(-1) OZ, and 240 microg mL(-1) i-IC. Upon stimulation with OZ or i-IC, the tested flavonols reduced the human and rabbit neutrophil NOC in the same order of potency--quercetin and galangin were the most and the least potent, respectively. These compounds were around four times more effective in inhibiting the rabbit as compared to the human neutrophil NOC, respectively. The four flavonols were not toxic to human or rabbit neutrophils. The experimental conditions used are suitable for both the determination of human and rabbit neutrophil NOC and for the assessment of the modulatory effects of natural compounds on these activities. The relationship between the level of NOC and the inhibitory potency of the flavonols suggests that rabbit neutrophils can be useful experimental models to predict the effect of drugs on immune complex-stimulated human neutrophils.

  8. The Immunologic Injury Composite with Balloon Injury Leads to Dyslipidemia: A Robust Rabbit Model of Human Atherosclerosis and Vulnerable Plaque

    PubMed Central

    Zhang, Guangyin; Li, Ming; Li, Liangjun; Xu, Yingzhi; Li, Peng; Yang, Cui; Zhou, Yanan; Zhang, Junping

    2012-01-01

    Atherosclerosis is a condition in which a lipid deposition, thrombus formation, immune cell infiltration, and a chronic inflammatory response, but its systemic study has been hampered by the lack of suitable animal models, especially in herbalism fields. We have tried to perform a perfect animal model that completely replicates the stages of human atherosclerosis. This is the first combined study about the immunologic injury and balloon injury based on the cholesterol diet. In this study, we developed a modified protocol of the white rabbit model that could represent a novel approach to studying human atherosclerosis and vulnerable plaque. PMID:22988422

  9. Lymphatic drainage of the skull base: comparative anatomic and advanced imaging studies in the rabbit and human with implications for spread of nasopharyngeal carcinoma.

    PubMed

    Qiuhang, Z; Zhenlin, W; Yan, Q; Jun, H; Yongfeng, S; Bo, H

    2010-09-01

    This preliminary study investigated the lymphatic drainage and distribution of lymphatic structures in the skull base. Characteristics of the rabbit skull base were analyzed and compared correspondingly with those of the human skull. The lymphatic circulation in the rabbit cranial base was detected by digital subtraction angiography (DSA), and lymph drainage in the human skull base was illustrated by interstitial magnetic resonance lymphography (MRL). Lymphatic structures and their distribution in MRL were identified by comparing with contrast-enhanced MRI and clinical data on basilar metastasis of nasopharyngeal carcinoma (NPC) in the human skull base. Anatomic similarity was found between the rabbit and human basilar regions. Well-visualized lymphatic pathways were found in the rabbit cranial base, and human lymphatic structures showed high signal intensity in enhanced T1-weighted MRL images. Lymphatic tissues in the human basilar region were found mainly distributed in the areas of the jugular foramen, foramen lacerum, and petrosal section of the internal carotid artery (ICA). Their distribution in the human basilar region was similar to the distribution in the rabbit basilar region and consistent with our clinical findings of the predilection sites of NPC metastasis in the skull base. Our studies show that bilateral symmetrical lymphatic structures were distributed along the ICA, internal jugular vein, and dura of cranial base in the central part of the middle and posterior skull base.

  10. Blockage of Src by Specific siRNA as a Novel Therapeutic Strategy to Prevent Destructive Repair in Steroid-Associated Osteonecrosis in Rabbits.

    PubMed

    Zheng, Li-zhen; Cao, Hui-juan; Chen, Shi-hui; Tang, Tao; Fu, Wei-min; Huang, Le; Chow, Dick Ho Kiu; Wang, Yi-xiang; Griffith, James Francis; He, Wei; Zhou, Hong; Zhao, De-wei; Zhang, Ge; Wang, Xin-luan; Qin, Ling

    2015-11-01

    Vascular hyperpermeability and highly upregulated bone resorption in the destructive repair progress of steroid-associated osteonecrosis (SAON) are associated with a high expression of VEGF and high Src activity (Src is encoded by the cellular sarcoma [c-src] gene). This study was designed to prove our hypothesis that blocking the VEGF-Src signaling pathway by specific Src siRNA is able to prevent destructive repair in a SAON rabbit model. Destructive repair in SAON was induced in rabbits. At 2, 4, and 6 weeks after SAON induction, VEGF, anti-VEGF, Src siRNA, Src siRNA+VEGF, control siRNA, and saline were introduced via intramedullary injection into proximal femora for each group, respectively. Vascularization and permeability were quantified by dynamic contrast-enhanced (DCE) MRI. At week 6 after SAON induction, proximal femurs were dissected for micro-computed tomography (μCT)-based trabecular architecture with finite element analysis (FEA), μCT-based angiography, and histological analysis. Histological evaluation revealed that VEGF enhanced destructive repair, whereas anti-VEGF prevented destructive repair and Src siRNA and Src siRNA+VEGF prevented destructive repair and enhanced reparative osteogenesis. Findings of angiography and histomorphometry were consistent with those determined by DCE MRI. Src siRNA inhibited VEGF-mediated vascular hyperpermeability but preserved VEGF-induced neovascularization. Bone resorption was enhanced in the VEGF group and inhibited in the anti-VEGF, Src siRNA, Src siRNA+VEGF groups as determined by both 3D μCT and 2D histomorphometry. FEA showed higher estimated failure load in the Src siRNA and Src siRNA+VEGF groups when compared to the vehicle control group. Blockage of VEGF-Src signaling pathway by specific Src siRNA was able to prevent steroid-associated destructive repair while improving reconstructive repair in SAON, which might become a novel therapeutic strategy.

  11. Engraftment Potential of Adipose Tissue-Derived Human Mesenchymal Stem Cells After Transplantation in the Fetal Rabbit

    PubMed Central

    Martínez-González, Itziar; Moreno, Rafael; Petriz, Jordi; Gratacós, Eduard

    2012-01-01

    Due to their favorable intrinsic features, including engraftment, differentiation, and immunomodulatory potential, adult mesenchymal stem cells (MSCs) have been proposed for therapeutic in utero intervention. Further improvement of such attributes for particular diseases might merely be achieved by ex vivo MSC genetic engineering previous to transplantation. Here, we evaluated for the first time the feasibility, biodistribution, long-term engraftment, and transgenic enhanced green fluorescent protein (EGFP) expression of genetically engineered human adipose tissue-derived MSCs (EGFP+-ASCs) after intra-amniotic xenotransplantation at E17 of gestation into our validated pregnant rabbit model. Overall, the procedure was safe (86.4% survival rate; absence of anatomical defects). Stable, low-level engraftment of EGFP+-ASCs was confirmed by assessing the presence of the pWT-EGFP lentiviral provirus in the young transplanted rabbit tissues. Accordingly, similar frequencies of provirus-positive animals were found at both 8 weeks (60%) and 16 weeks (66.7%) after in utero intervention. The presence of EGFP+-ASCs was more frequent in respiratory epithelia (lung and trachea), according to the route of administration. However, we were unable to detect EGFP expression, neither by real-time polymerase chain reaction nor by immunohistochemistry, in the provirus-positive tissues, suggesting EGFP transgene silencing mediated by epigenetic events. Moreover, we noticed lack of both host cellular immune responses against xenogeneic ASCs and humoral immune responses against transgenic EGFP. Therefore, the fetal microchimerism achieved by the EGFP+-ASCs in the young rabbit hosts indicates induction of donor-specific tolerance after fetal rabbit xenotransplantation, which should boost postnatal transplantation for the early treatment/prevention of many devastating congenital disorders. PMID:22738094

  12. Use of human amniotic membrane wrap in reducing perineural adhesions in a rabbit model of ulnar nerve neurorrhaphy.

    PubMed

    Kim, S S; Sohn, S K; Lee, K Y; Lee, M J; Roh, M S; Kim, C H

    2010-03-01

    The object of this experimental study was to assess the effect of wrapping human amniotic membrane around a repaired ulnar nerve in a rabbit model of perineural adhesion. Ulnar nerves from 10 white New Zealand rabbits were exposed bilaterally, dissected and repaired. Human amniotic membrane was then wrapped around the repair site in one limb with no such wrap in the neurorrhaphy of the contralateral limb. Three months later, the same nerves were re-explored and removed using microsurgical external neurolysis. Perineural adhesion around the ulnar nerve was evaluated by blinded surgical dissection and scored using a visual 4-point qualitative scale. Extent and grade of fibrosis around repair sites were measured microscopically (x 200) after Masson trichrome staining using measure of the depth of fibrosis and the grading criteria of adhesion. Quantitative morphometric analysis was also performed under light microscopy (x 200) with the aid of a digital counter and virtual slide imaging software (ScanScope T2, Vista, CA, USA). Human amniotic membrane wrapped nerves showed significantly less perineural adhesion and fibrosis than controls (P < 0.05). No nerve healing problems were encountered. This study suggests that human amniotic membrane application can reduce fibrosis and adhesion around neurorrhaphy sites in this animal model.

  13. 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.

  14. In vitro CD4+ lymphocyte transformation and infection in a rabbit model with a molecular clone of human T-cell lymphotrophic virus type 1.

    PubMed Central

    Collins, N D; Newbound, G C; Ratner, L; Lairmore, M D

    1996-01-01

    We transfected human and rabbit peripheral blood mononuclear cells (PBMC) with the ACH molecular clone of human T-cell lymphotropic virus type 1 (HTLV-1) to study its in vitro and in vivo properties. PBMC transfected with ACH were shown to transfer infection to naive PBMC. ACH transformed rabbit PBMC, as indicated by interleukin-2-independent proliferation of a transfectant culture. This transformant culture was shown by flow cytometric analysis to be a CD4+ CD25+ T-lymphocyte population containing, as determined by Southern blot analysis, at least three integrated HTLV-1 proviral copies. HTLV-1 infection was produced in rabbits inoculated with ACH-transfected, irradiated PBMC. Inoculated rabbits seroconverted to positivity for antibodies against HTLV-1 and had steady or rising HTLV-1 enzyme-linked immunosorbent assay antibody titers. Western blot (immunoblot) analysis revealed sustained seroconversion of rabbits to positivity for antibodies against all major viral antigenic determinants. Infection of rabbits was further demonstrated by antigen capture assay of p24 in PBMC and lymph node cultures and PCR amplification of proviral sequences from PBMC. These data suggest that ACH, like wild-type HTLV-1, infects and transforms primary CD4+ T lymphocytes and is infectious in vivo. This clone will facilitate investigations into the role of viral genes on biological properties of HTLV-1 in vitro and in vivo. PMID:8794375

  15. Disposable rabbit

    DOEpatents

    Lewis, Leroy C.; Trammell, David R.

    1986-01-01

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

  16. Disposal rabbit

    DOEpatents

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

    1983-10-12

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

  17. Effects of recombinant human interleukin-10 on Treg cells, IL-10 and TGF-β in transplantation of rabbit skin.

    PubMed

    Liu, Kai Shan; Fan, Xiao Qin; Zhang, Lei; Wen, Qiong Na; Feng, Ji Hong; Chen, Fu Chao; Luo, Jun Min; Sun, Wan Bang

    2014-02-01

    The current study aimed to investigate the rejection and survival time of grafted skin, and the changes of Treg cells, interleukin 10 (IL-10) and transforming growth factor-β (TGF-β) in peripheral blood following skin transplantation with recombinant human interleukin-10 (rhIL-10) or cyclosporin A (CsA), as well as the role of IL-10 in immunological rejection mechanisms. A total of 36 rabbits were divided into two groups. The skin of a donor rabbit was transplanted onto the back of one receptor rabbit. Receptors were randomly divided into six groups, including rhIL-10 low-dose (5 µg/kg/d), rhIL-10 high-dose (10 µg/kg/d), CsA low-dose (5 mg/kg/d), CsA high-dose (10 mg/kg/d), rhIL-10 (5 µg/kg/d) and CsA (5 mg/kg/d) and negative control normal saline (NS; 1 ml/d). All groups received intramuscular drug injection for ten days, beginning one day prior to skin transplantation surgery. Following transplantation, each rabbit's peripheral blood was collected at different times. The changes of CD4+CD25+ regulatory T cells, IL-10 and TGF-β were determined by flow cytometry and enzyme-linked immunosorbent assay. When compared with the control group, the rejection and survival times of the experimental groups were longer following skin graft. Compared with the two CsA groups and the control group, the proportion of CD4+CD25+ regulatory T cells of rhIL-10 groups was significantly upregulated on the 4th and 7th days following surgery. However, TGF-β levels were not significantly different. Data suggested that the concentration of IL-10 was positively correlated with the proportion of CD4+CD25+ regulatory T cells. In addition, IL-10 may delay the rejection time of rabbit skin transplantation and prolong the survival time. Thus, the role of IL-10 in inhibited allograft rejection may be associated with CD4+CD25+ regulatory T cells and IL-10, and may be independent of TGF-β.

  18. Magnetic resonance knee arthrography. Enhanced contrast by gadolinium complex in the rabbit and in humans.

    PubMed

    Engel, A

    1990-01-01

    This study contains the fundamentals and the technique of the intraarticular application of an MRI contrast agent in connection with magnetic resonance imaging (MRI arthrography). It also presents the resulting clinical relevance for knee joint diagnostics. The significance of MRI arthrography is linked above all to the central question of whether or not it is possible to depict the hyaline cartilage, its surface and its thickness with the help of MRI arthrography. MRI arthrography was used for in vitro examinations of rabbit knee joint cartilage and human joint cartilage. The in vivo application was carried out in 73 patients. Apart from the metric evaluation and the assessment of the information content of the MRI image, the corresponding histologic sections were made in 20 knee joints in order to compare the cartilage surface and the thickness of the cartilage with the results in the MRI image. The optimum amount of contrast agent for visualization was determined, the uptake and clearance of the contrast agent from the cartilage were assessed, and trace elements from the cartilage were also analyzed. The examination showed that the molecular structure of the contrast agent (gadolinium-DTPA) does not prevent the uptake of the contrast agent into the matrix of the hyaline cartilage. But this process is reversible. Thus, 14 hours after the intraarticular application of the contrast agent no measurable traces of gadolinium-DTPA could be established. The intraarticular application of the contrast agent also made it possible to achieve a constant and reproducible visualization of all joint structures. This affected mainly the surface of the hyaline cartilage. The best imaging quality was achieved with intraarticular application of 30 to 40 mL of a 2 mmolar solution of gadolinium-DTPA. The technique used for the intraarticular application is the same as for the common procedures of knee joint aspiration. The clinical importance of MRI arthrography lies in the fact that

  19. Development of humanized rabbit monoclonal antibodies against vascular endothelial growth factor receptor 2 with potential antitumor effects.

    PubMed

    Yu, Yanlan; Lee, Pierre; Ke, Yaohuang; Zhang, Yongke; Chen, Jungang; Dai, Jihong; Li, Mingzhen; Zhu, Weimin; Yu, Guo-Liang

    2013-07-05

    Vascular endothelial growth factor-A (VEGF-A) plays a critical role in physiologic and pathologic angiogenesis through its receptors especially through VEGFR2. The lack of cross-reactivity of monoclonal antibodies with human VEGFR2/mouse Flk-1 is a major obstacle in preclinical developments. In this study, using a unique hybridoma technique, we generated a panel of 30 neutralization anti-VEGFR2 rabbit monoclonal antibodies (RabMAbs) either blocking VEGF/VEGFR2 interaction or inhibiting VEGF-stimulated VEGFR2 tyrosine kinase phosphorylation. Among 18 RabMAbs with human/mouse VEGFR2 cross-reactivity, we humanized one lead candidate RabMAb by Mutational Lineage Guided (MLG) method and further demonstrated its potent inhibition of tumor growth in xenograft mouse model. Our study suggests that RabMAbs are highly relevant for therapeutic applications.

  20. Auditory Distance Coding in Rabbit Midbrain Neurons and Human Perception: Monaural Amplitude Modulation Depth as a Cue

    PubMed Central

    Zahorik, Pavel; Carney, Laurel H.; Bishop, Brian B.; Kuwada, Shigeyuki

    2015-01-01

    Mechanisms underlying sound source distance localization are not well understood. Here we tested the hypothesis that a novel mechanism can create monaural distance sensitivity: a combination of auditory midbrain neurons' sensitivity to amplitude modulation (AM) depth and distance-dependent loss of AM in reverberation. We used virtual auditory space (VAS) methods for sounds at various distances in anechoic and reverberant environments. Stimulus level was constant across distance. With increasing modulation depth, some rabbit inferior colliculus neurons increased firing rates whereas others decreased. These neurons exhibited monotonic relationships between firing rates and distance for monaurally presented noise when two conditions were met: (1) the sound had AM, and (2) the environment was reverberant. The firing rates as a function of distance remained approximately constant without AM in either environment and, in an anechoic condition, even with AM. We corroborated this finding by reproducing the distance sensitivity using a neural model. We also conducted a human psychophysical study using similar methods. Normal-hearing listeners reported perceived distance in response to monaural 1 octave 4 kHz noise source sounds presented at distances of 35–200 cm. We found parallels between the rabbit neural and human responses. In both, sound distance could be discriminated only if the monaural sound in reverberation had AM. These observations support the hypothesis. When other cues are available (e.g., in binaural hearing), how much the auditory system actually uses the AM as a distance cue remains to be determined. PMID:25834060

  1. [Electrophysiological analysis of bruxisma of rabbits as natural model of the first bruxism in human being].

    PubMed

    Ignatova, Iu P; Kromin, A A

    2010-01-01

    In chronic experiences on 5 rabbits subjected to airmentary deprivation, impulse activity of the chewing muscles before and after the food was given to them was studied. It has been established, that flashes of bruxism nonoperiodically arise in rabbits in conditions of hunger and satiation and are shown in electric activity of masseter and mylohyoideus muscles in the form of burst type phase impulse activity of MU. Bruxism in conditions of hunger and satiation reflects in the same type way in structure of the time organization of impulse activity of the chewing muscles in the form of bimodal distributions of interpulse intervals and monomodal distributions of periods of the burst type rhythmic of action potentials. The alimentary motivation exerts inhibitory modulating influence on frequency of phase discharge activity of chewing center motoneurons in medulla oblongata and frequency of generation of the action potentials' bursts by the chewing muscles participating in bruxism. Impulse activity of chewing muscles during bruxism and food intake behaviour has the same-type character. Bruxism arises due to reorganization of the impulse activity of chewing center motoneurons innervating masseter and mylohyoideus muscles. There is no basis to suppose the presence of the special center of bruxism in medulla oblongata.Bruxism in rabbits an be considered as natural model of the first type bruxism in man.

  2. From rabbit antibody repertoires to rabbit monoclonal antibodies

    PubMed Central

    Weber, Justus; Peng, Haiyong; Rader, Christoph

    2017-01-01

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

  3. Recombinant human bone morphogenetic protein-2 suspended in fibrin glue enhances bone formation during distraction osteogenesis in rabbits

    PubMed Central

    Li, Yunfeng; Li, Rui; Hu, Jing; Song, Donghui; Jiang, Xiaowen

    2016-01-01

    Introduction Bone morphogenetic protein-2 (BMP-2) has high potential for bone formation, but its in vivo effects are unpredictable due to the short life time. This study was designed to evaluate the effects of recombinant human (rh) BMP-2 suspended in fibrin on bone formation during distraction osteogenesis (DO) in rabbits. Material and methods The in vitro release kinetics of rhBMP-2 suspended in fibrin was tested using an enzyme-linked immunosorbent assay. Unilateral tibial lengthening for 10 mm was achieved in 48 rabbits. At the completion of osteodistraction, vehicle, fibrin, rhBMP-2 or rhBMP-2 suspended in fibrin (rhBMP-2 + fibrin) was injected into the center of the lengthened gap, with 12 animals in each group. Eight weeks later, the distracted callus was examined by histology, micro-CT and biomechanical testing. Radiographs of the distracted tibiae were taken at both 4 and 8 weeks after drug treatment. Results It was found that fibrin prolonged the life span of rhBMP-2 in vitro with sustained release during 17 days. The rhBMP-2 + fibrin treated animals showed the best results in bone mineral density, bone volume fraction, cortical bone thickness by micro-CT evaluation and mechanical properties by the three-point bending test when compared to the other groups (p < 0.05). In histological images, rhBMP-2 + fibrin treatment showed increased callus formation and better gap bridging compared to the other groups. Conclusions The results of this study suggest that fibrin holds promise to be a good carrier of rhBMP-2, and rhBMP-2 suspended in fibrin showed a stronger promoting effect on bone formation during DO in rabbits. PMID:27279839

  4. Mechanism of vasodilation induced by alpha-human atrial natriuretic polypeptide in rabbit and guinea-pig renal arteries.

    PubMed Central

    Fujii, K; Ishimatsu, T; Kuriyama, H

    1986-01-01

    Effects of alpha-human atrial natriuretic polypeptide (alpha-HANP) on electrical and mechanical properties of smooth muscle cells of the guinea-pig and rabbit renal arteries and of the guinea-pig mesenteric artery were investigated. alpha-HANP (up to 10 nM) modified neither the membrane potential nor resistance of smooth muscle cells of the guinea-pig and rabbit renal arteries. In the guinea-pig mesenteric and renal arteries, alpha-HANP (up to 10 nM) had no effect on the amplitude and facilitation (mesenteric artery) or depression (renal artery) of excitatory junction potentials nor on action potentials. In the guinea-pig renal artery, alpha-HANP (up to 10 nM) had no effect on the depolarization induced by noradrenaline (NA) (up to 10 microM) but markedly inhibited NA-induced contraction. alpha-HANP (10 nM) slightly inhibited the K-induced contraction. In the rabbit renal artery, alpha-HANP (10 nM) inhibited the NA-induced contraction and to a lesser extent the K-induced contraction. In the rabbit renal artery, the effects of alpha-HANP on the release of Ca from the cellular storage by two applications of NA, and its re-storage, were investigated in Ca-free solution containing 2 mM-EGTA. When 5 nM-alpha-HANP was applied before and during the first application of 0.5 microM-NA, the contraction was markedly inhibited but the contraction to a second application of 10 microM-NA was potentiated. If the first dose of NA was 10 microM the effect was very small. Under the same experimental procedures, nitroglycerine (10 microM) showed almost the same effects as alpha-HANP on the NA-induced contractions. When both the first (3 mM) and second (10 mM) contractions were evoked by caffeine in Ca-free solution, alpha-HANP (5 nM) and nitroglycerine (10 microM) inhibited both contractions to the same extent. In the rabbit renal artery, applications of alpha-HANP or nitroglycerine increased the amount of guanosine 3',5'-phosphate (cyclic GMP) in a dose-dependent manner. However, a

  5. Repair of Osteochondral Defects Using Human Umbilical Cord Wharton's Jelly-Derived Mesenchymal Stem Cells in a Rabbit Model.

    PubMed

    Liu, Shuyun; Jia, Yanhui; Yuan, Mei; Guo, Weimin; Huang, Jingxiang; Zhao, Bin; Peng, Jiang; Xu, Wenjing; Lu, Shibi; Guo, Quanyi

    2017-01-01

    Umbilical cord Wharton's jelly-derived mesenchymal stem cell (WJMSC) is a new-found mesenchymal stem cell in recent years with multiple lineage potential. Due to its abundant resources, no damage procurement, and lower immunogenicity than other adult MSCs, WJMSC promises to be a good xenogenous cell candidate for tissue engineering. This in vivo pilot study explored the use of human umbilical cord Wharton's jelly mesenchymal stem cells (hWJMSCs) containing a tissue engineering construct xenotransplant in rabbits to repair full-thickness cartilage defects in the femoral patellar groove. We observed orderly spatial-temporal remodeling of hWJMSCs into cartilage tissues during repair over 16 months, with characteristic architectural features, including a hyaline-like neocartilage layer with good surface regularity, complete integration with adjacent host cartilage, and regenerated subchondral bone. No immune rejection was detected when xenograft hWJMSCs were implanted into rabbit cartilage defects. The repair results using hWJMSCs were superior to those of chondrogenically induced hWJMSCs after assessing gross appearance and histological grading scores. These preliminary results suggest that using novel undifferentiated hWJMSCs as seed cells might be a better approach than using transforming growth factor-β-induced differentiated hWJMSCs for in vivo tissue engineering treatment of cartilage defects. hWJMSC allografts may be promising for clinical applications.

  6. Repair of Osteochondral Defects Using Human Umbilical Cord Wharton's Jelly-Derived Mesenchymal Stem Cells in a Rabbit Model

    PubMed Central

    Jia, Yanhui; Yuan, Mei; Guo, Weimin; Huang, Jingxiang; Zhao, Bin; Xu, Wenjing; Lu, Shibi

    2017-01-01

    Umbilical cord Wharton's jelly-derived mesenchymal stem cell (WJMSC) is a new-found mesenchymal stem cell in recent years with multiple lineage potential. Due to its abundant resources, no damage procurement, and lower immunogenicity than other adult MSCs, WJMSC promises to be a good xenogenous cell candidate for tissue engineering. This in vivo pilot study explored the use of human umbilical cord Wharton's jelly mesenchymal stem cells (hWJMSCs) containing a tissue engineering construct xenotransplant in rabbits to repair full-thickness cartilage defects in the femoral patellar groove. We observed orderly spatial-temporal remodeling of hWJMSCs into cartilage tissues during repair over 16 months, with characteristic architectural features, including a hyaline-like neocartilage layer with good surface regularity, complete integration with adjacent host cartilage, and regenerated subchondral bone. No immune rejection was detected when xenograft hWJMSCs were implanted into rabbit cartilage defects. The repair results using hWJMSCs were superior to those of chondrogenically induced hWJMSCs after assessing gross appearance and histological grading scores. These preliminary results suggest that using novel undifferentiated hWJMSCs as seed cells might be a better approach than using transforming growth factor-β-induced differentiated hWJMSCs for in vivo tissue engineering treatment of cartilage defects. hWJMSC allografts may be promising for clinical applications. PMID:28261617

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

    PubMed

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

    2005-02-01

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

  8. Development of a cytotoxic T-cell assay in rabbits to evaluate early immune response to human T-lymphotropic virus type 1 infection.

    PubMed

    Haynes, Rashade A H; Phipps, Andrew J; Yamamoto, Brenda; Green, Patrick; Lairmore, Michael D

    2009-12-01

    Human T-lymphotropic virus type 1 (HTLV-1) infection causes adult T-cell lymphoma/leukemia (ATL) following a prolonged clinical incubation period, despite a robust adaptive immune response against the virus. Early immune responses that allow establishment of the infection are difficult to study without effective animal models. We have developed a cytotoxic T-lymphocyte (CTL) assay to monitor the early events of HTLV-1 infection in rabbits. Rabbit skin fibroblast cell lines were established by transformation with a plasmid expressing simian virus 40 (SV40) large T antigen and used as autochthonous targets (derived from same individual animal) to measure CTL activity against HTLV-1 infection in rabbits. Recombinant vaccinia virus (rVV) constructs expressing either HTLV-1 envelope surface unit (SU) glycoprotein 46 or Tax proteins were used to infect fibroblast targets in a (51)Cr-release CTL assay. Rabbits inoculated with Jurkat T cells or ACH.2 cells (expressing ACH HTLV-1 molecule clone) were monitored at 0, 2, 4, 6, 8, 13, 21, and 34 wk post-infection. ACH.2-inoculated rabbits were monitored serologically and for viral infected cells following ex vivo culture. Proviral load analysis indicated that rabbits with higher proviral loads had significant CTL activity against HTLV-1 SU as early as 2 wk post-infection, while both low- and high-proviral-load groups had minimal Tax-specific CTL activity throughout the study. This first development of a stringent assay to measure HTLV-1 SU and Tax-specific CTL assay in the rabbit model will enhance immunopathogenesis studies of HTLV-1 infection. Our data suggest that during the early weeks following infection, HTLV-1-specific CTL responses are primarily targeted against Env-SU.

  9. Common-path Fourier domain optical coherence tomography of irradiated human skin and ventilated isolated rabbit lungs

    NASA Astrophysics Data System (ADS)

    Popp, A.; Wendel, M.; Knels, L.; Knuschke, P.; Mehner, M.; Koch, T.; Boller, D.; Koch, P.; Koch, E.

    2005-08-01

    A compact common path Fourier domain optical coherence tomography (FD-OCT) system based on a broadband superluminescence diode is used for biomedical imaging. The epidermal thickening of human skin after exposure to ultraviolet radiation is measured to proof the feasibility of FD-OCT for future substitution of invasive biopsies in a long term study on natural UV skin protection. The FD-OCT system is also used for imaging lung parenchyma. FD-OCT images of a formalin fixated lung show the same alveolar structure as scanning electron microscopy images. In the ventilated and blood-free perfused isolated rabbit lung FD-OCT is used for real-time cross-sectional image capture of alveolar mechanics throughout tidal ventilation. The alveolar mechanics changing from alternating recruitment-derecruitment at zero positive end-expiratory pressure (PEEP) to persistent recruitment after applying a PEEP of 5 cm H2O is observed in the OCT images.

  10. Photoaffinity labeling of human platelet and rabbit kidney. cap alpha. -adrenoceptors with (/sup 3/H)SKF 102229

    SciTech Connect

    Regan, J.W.; Raymond, J.R.; Lefkowitz, R.J.; DeMarinis, R.M.

    1986-06-13

    A newly developed ..cap alpha../sub 2/-adrenergic photoaffinity ligand, 3-methyl-6-chloro-9-azido-1H-2,3,4,5-tetrahydro-3-benzazepine (SKF 102229), has been radiolabeled with tritium to a specific activity of approx. 80 Ci/mmol. Using membranes prepared from human platelets and from rabbit kidney, ..cap alpha../sub 2/-adrenoceptors have been covalently labeled following photolysis in the presence of (/sup 3/H)SKF 102229. As determined by SDS-PAGE, the apparent molecular weight of ..cap alpha../sub 2/-adrenoceptors from both of these tissues was 64,000. The yield of covalent insertion of (/sup 3/H)SKF 102229 into the ..cap alpha../sub 2/-adrenoceptor was very good. Thus, following photolysis up to 90% of the ..cap alpha../sub 2/-adrenoceptors could be irreversibly labeled with (/sup 3/H)SKF 102229.

  11. Comparative studies on neutralisation of primary HIV-1 isolates by human sera and rabbit anti-V3 peptide sera.

    PubMed

    Lawoko, A L; Johansson, B; Hjalmarsson, S; Christensson, B; Ljungberg, B; Al-Khalili, L; Sjölund, M; Pipkorn, R; Fenyö, E M; Blomberg, J

    1999-10-01

    IgG binding to V3 peptides and serum neutralising responses were studied in four HIV-1 infected individuals with progressive disease over a period of 31-70 months. The 18-20 mer peptides comprised residues 299-317 (numbering of HIV1 MN) in the N-terminal half of the V3 loop of the envelope glycoprotein gp120 and were derived from the sequences of autologous, as well as heterologous isolates. All four individuals studied lacked anti-V3 IgG binding to at least one autologous V3 sequence. V3 peptides to which autologous sera lacked binding IgG were all immunogenic in rabbits and induced antisera that were broadly cross-reactive by EIA and broadly cross-neutralising to primary HIV-1 isolates. This indicates that the peptides are immunogenic per se and that the respective human hosts have selective defects in recognising the corresponding V3 sequences. Despite the absence of antibody binding to autologous V3 peptides, the human sera had neutralising antibodies to autologous (three out of four cases), as well as heterologous isolates (all cases). Moreover, in vitro exposure of the patients' isolates to autologous neutralising serum or the homologous rabbit antiserum selected for variants with amino acid substitutions close to the crown of the V3 loop or in regions outside the sequence corresponding to peptides used for immunisation. The amino acid exchanges affected V3 positions known to be antigenic and which are also prone to change successively in infected persons. It is likely that neutralising antibodies recognise both linear and conformational epitopes in the V3 loop. Apparently, there are several, but restricted, numbers of ways for this structure to change its conformation and thereby give rise to neutralisation resistant viruses.

  12. A peptide derived from the human leptin molecule is a potent inhibitor of the leptin receptor function in rabbit endometrial cells.

    PubMed

    Gonzalez, Ruben Rene; Leavis, Paul C

    2003-07-01

    In this article we show that rabbit endometrial cells express leptin receptor and that human leptin triggers phosphorylation of signal transducer and activator of transcription 3 and up-regulates the expression of interleukin- 1 receptor type I as was previously found in human endometrial cells. Interestingly, leptin also upregulates the secretion of leukemia inhibitory factor and expression of its receptor by rabbit endometrial cells. Analysis of a structural model of the leptin-leptin receptor complex suggested that helices I and III of the human leptin structure were likely sites of interaction with the cytokine binding domain of leptin receptor. Accordingly, we synthesized a peptide (LPA-2) comprising helix III (residues 70-95) and investigated its ability to inhibit leptin receptor function. The effects of LPA-2 were assayed in rabbit endometrial cells, and an antileptin receptor antibody and a scrambled version of LPA-2 were used as positive and negative controls, respectively. LPA-2 binds specifically and with high affinity (Ki ~ 0.6 x 10-10 M) to leptin receptor and is a potent inhibitor of its functions in rabbit endometrial cells. Because leukemia inhibitory factor and interleukin- 1 have been implicated in embryo implantation, our results raise the possibility that the LPA-2-induced inhibition of leptin receptor may be exploited to study the actions of leptin in endometrium and in other tissues under conditions characterized by abnormal leptin production.

  13. High-level expression of a novel recombinant human plasminogen activator (rhPA) in the milk of transgenic rabbits and its thrombolytic bioactivity in vitro.

    PubMed

    Song, Shaozheng; Ge, Xin; Cheng, Yaobin; Lu, Rui; Zhang, Ting; Yu, Baoli; Ji, Xueqiao; Qi, Zhengqiang; Rong, Yao; Yuan, Yuguo; Cheng, Yong

    2016-08-01

    The human tissue-type plasminogen activator (tPA) is a key kinase of fibrinolysis that plays an important role in dissolving fibrin clots to promote thrombolysis. The recombinant human plasminogen activator (rhPA) has more thrombolytic advantages than the wild type tPA. To increase the half-life and thrombolytic activity of tPA, a mutant containing only the essential K2 fibrin-binding and P activating plasminogen domains of the wild type tPA was cloned. This fragment was then inserted into goat β-casein regulatory sequences. Then, a mammary gland-specific expression vector, PCL25/rhPA, was constructed, and the transgenic rabbits were generated. In this study, 18 live transgenic founders (12♀, 6♂) were generated using pronuclear microinjection. Six transgenic rabbits were obtained, and the expression levels of rhPA in the milk had a range of 15.2-630 µg/ml. A fibrin agarose plate assay of rhPA showed that it had strong thrombolytic bioactivity in vitro, and the highest specific activity was >360 (360 times more than that of alteplase). The results indicated that the rhPA containing only the K2 and P domains is efficiently expressed with higher thrombolytic bioactivity in the milk of transgenic rabbits. Our study also demonstrated a new method for the large-scale production of clinically relevant recombinant pharmaceutical proteins in the mammary glands of transgenic rabbits.

  14. Pharmacokinetics of topically applied recombinant human keratinocyte growth factor-2 in alkali-burned and intact rabbit eye.

    PubMed

    Cai, Jianqiu; Dou, Guifang; Zheng, Long; Yang, Ting; Jia, Xuechao; Tang, Lu; Huang, Yadong; Wu, Wencan; Li, Xiaokun; Wang, Xiaojie

    2015-07-01

    Keratinocyte growth factor-2 (KGF-2), an effective agent in the development of epithelial tissue and regeneration during corneal wound healing, is a potential therapeutic option to treat the corneal diseases with corneal epithelial defects. However the tissue distribution and pharmacokinetics of KGF-2 have not been explored yet in eye upon topical application. Using (125)I-labeled recombinant human KGF-2 ((125)I-rhKGF-2), tissue distribution of rhKGF-2 in alkali-burned and control rabbit eyes was studied. Our results revealed that (125)I-rhKGF-2 was distributed to all eye tissues examined. The highest radioactivity level was found in the cornea, followed by iris, sclera, ciliary body, lens, aqueous humor, vitreous body, and serum in a greatest to least order. The levels of (125)I-rhKGF-2 were higher in corneas of alkali-burned eyes than those in control eyes though without statistical significance. Calculated pharmacokinetic parameters of t1/2, Cmax, and Tmax of rhKGF-2 in the rabbit corneas were 3.4 h, 135.2 ng/ml, and 0.5 h, respectively. In iris, lens, aqueous humor, and tear, t1/2, Cmax, and Tmax values were 6.2, 6.5, 5.2, and 2.5 h; 23.2, 4.5, 24.1, and 29,498.9 ng/ml; and 1.0, 0.5, 0.5, and 1.0 h, respectively. Predominant and rapid accumulation of rhKGF-2 in corneas suggests that therapeutic doses of rhKGF-2 could be delivered by topical application for treatment of corneal diseases.

  15. The presence of liver auto-antibodies induced by Entamoeba histolytica in the sera from both naturally infected humans and immunized rabbits.

    PubMed

    Faubert, G M; Meerovitch, E; McLaughlin, J

    1978-09-01

    Auto-antibodies against normal human liver have been detected in the sera of humans with highly positive indirect hemagglutination (IHA) amebiasis titers and with clinically-proven amebic liver abscess. Sera of amebiasis patients and rabbits immunized with killed Entamoeba histolytica were tested for anti-amebic antibodies by the IHA test and for auto-antibodies by the complement fixation test, using the antigens prepared from extracts of human liver and rabbit liver. A direct correlation was found to exist between high anti-Entamoeba antibody titers and the presence of anti-liver antibody in the serum. It is proposed that, in addition to direct parasite damage to host tissue, immunological damage could result from the attachment of circulating antigen to the cell surfaces of host tissues such as the liver.

  16. An immunohistochemical study of human platelets using a rabbit antibody against H18-K24 of apolipoprotein CIII (HATKTAK).

    PubMed

    Yamanaka, Takao; Sakamoto, Haruhiko; Nakagawa, Toshitaka; Tanaka, Sumiko; Matsumoto, Kouichi; Ueno, Masaki

    2013-08-01

    H18-K24 of human apolipopotein CIII (Apo CIII) (HATKTAK) is an activator of the macromolecular activators of phagocytosis from platelets (MAPPs). Using a rabbit antibody against HATKTAK, we performed an immunohistochemical study of human platelets. Indirect ELISA showed that this antibody reacts with Apo CIII-derived peptides with a C-terminal of HATKTAK, but not with Apo CIII. Immunoelectron microscopy revealed that reaction of anti-HATKTAK antibody occurred in the pseudopods of activated platelets. In blood coagula produced from the peripheral blood and formalin-fixed after various incubation periods, reaction of this antibody with platelets appeared rapidly with a peak at 3 to 6 h of incubation, and then diminished gradually. Leukocytes in the blood coagula were stained strongly positive. In tissue sections, fresh thrombi and hemorrhages with slight fibrin formation revealed a positive response of platelets to anti-HATKTAK antibody, whereas older ones with leukocytic infiltration, fibrin formation and organization did not. In addition to platelets, endothelial cells and leukocytes were stained positive by anti-HATKTAK antibody. All of the positive reactions by anti-HATKTAK antibody disappeared or diminished by co-incubation with HATKTAK. In conclusion, the anti-HATKTAK antibody reveals platelets during the early phase of activation.

  17. Efficient hydrolysis of the chemical warfare nerve agent tabun by recombinant and purified human and rabbit serum paraoxonase 1.

    PubMed

    Valiyaveettil, Manojkumar; Alamneh, Yonas; Biggemann, Lionel; Soojhawon, Iswarduth; Doctor, Bhupendra P; Nambiar, Madhusoodana P

    2010-12-03

    Paraoxonase 1 (PON1) has been described as an efficient catalytic bioscavenger due to its ability to hydrolyze organophosphates (OPs) and chemical warfare nerve agents (CWNAs). It is the future most promising candidate as prophylactic medical countermeasure against highly toxic OPs and CWNAs. Most of the studies conducted so far have been focused on the hydrolyzing potential of PON1 against nerve agents, sarin, soman, and VX. Here, we investigated the hydrolysis of tabun by PON1 with the objective of comparing the hydrolysis potential of human and rabbit serum purified and recombinant human PON1. The hydrolysis potential of PON1 against tabun, sarin, and soman was evaluated by using an acetylcholinesterase (AChE) back-titration Ellman method. Efficient hydrolysis of tabun (100 nM) was observed with ∼25-40 mU of PON1, while higher concentration (80-250 mU) of the enzyme was required for the complete hydrolysis of sarin (11 nM) and soman (3 nM). Our data indicate that tabun hydrolysis with PON1 was ∼30-60 times and ∼200-260 times more efficient than that with sarin and soman, respectively. Moreover, the catalytic activity of PON1 varies from source to source, which also reflects their efficiency of hydrolyzing different types of nerve agents. Thus, efficient hydrolysis of tabun by PON1 suggests its promising potential as a prophylactic treatment against tabun exposure.

  18. Comparison of the role of tyrosine residues in human IgG and rabbit IgG in binding of complement subcomponent C1q.

    PubMed Central

    McCall, M N; Easterbrook-Smith, S B

    1989-01-01

    Treatment of covalently cross-linked or heat-aggregated oligomers of human IgG with 4 mM-tetranitromethane abrogated their C1q-binding activity. In contrast, tetranitromethane modification of rabbit IgG oligomers, under identical conditions, had no effect upon their C1q-binding activity. The tetranitromethane treatment led to nitration of about ten tyrosine residues per IgG molecule in both species, and the modification was specific for tyrosine residues. Reduction of the nitrated protein with Na2S2O4 did not lead to recovery of C1q-binding activity in human IgG oligomers or to loss of activity in rabbit IgG oligomers. Tryptic peptides from the nitrated proteins were isolated and a peptide containing nitrotyrosine-319 was recovered from human IgG, as well as peptides from both species corresponding to the region around nitrotyrosine-278. These data are consistent with the inactivation of C1q-binding activity in human IgG being the result of nitration of tyrosine-319; the rabbit IgG is unaffected by nitration because position 319 is phenylalanine. The evidence supports the C1q-receptor site proposed by Burton, Boyd, Brampton, Easterbrook-Smith, Emanuel, Novotny, Rademacher, van Schravendijk, Sternberg & Dwek [(1980) Nature (London) 288, 338-344]: residues 316-338. PMID:2784672

  19. Expression of human factor IX in rabbit hepatocytes by retrovirus-mediated gene transfer: Potential for gene therapy of hemophilia B

    SciTech Connect

    Thompson, A.R. Puget Sound Blood Center, Seattle, WA ); Darlington, G. ); Armentano, D.; Woo, S.L.C.

    1990-08-01

    Hemophilia B (Christmas disease) is a chromosome X-linked blood clotting disorder which results when factor IX is deficient or functionally defective. The enzyme is synthesized in the liver, and the existence of animal models for this genetic disease will permit the development of somatic gene therapy protocols aimed at transfer of the functional gene into the liver. The authors report the construction of an N2-based recombinant retroviral vector, NCMVFIX, for efficient transfer and expression of human factor IX cDNA in primary rabbit hepatocytes. In this construct the human cytomegalovirus immediate early promoter directs the expression of factor IX. Hepatocytes were isolated from 3-week-old New Zealand White rabbits, infected with the recombinant virus, and analyzed for secretion of active factor IX. The infected rabbit hepatocytes produced human factor IX that is indistinguishable from enzyme derived from normal human plasma. The recombinant protein is sufficiently {gamma}-carboxylated and is functionally active in clotting assays. These results establish the feasibility of using infected hepatocytes for the expression of this protein and are a step toward the goal of correcting hemophilia B by hepatic gene transfer.

  20. Feasibility and Efficacy of Autologous Bone Marrow Aspirate Transplantation Combined with Human Parathyroid Hormone 1-34 Administration to Treat Osteonecrosis in a Rabbit Model

    PubMed Central

    Sugaya, Hisashi; Aoto, Katsuya; Uemura, Kenta; Tanaka, Kenta; Akaogi, Hiroshi; Yamazaki, Masashi; Mishima, Hajime

    2017-01-01

    No studies have examined the transplantation of a bone marrow aspirate (BMA) containing mesenchymal stem cells (MSCs) combined with human parathyroid hormone 1-34 (hPTH1-34) administration. Therefore, we evaluated the feasibility and efficacy of autologous BMA transplantation combined with hPHT1-34 administration in a bone necrosis model. The metatarsal bones of rabbits were necrotized using liquid nitrogen, and the rabbits received a BMA transplantation or saline injection followed by hPTH1-34 (30 μg/kg) or saline administration three times per week (n = 3-4 per group). The rabbits were euthanized at 12 weeks after the initiation of treatment. No systemic adverse effects or local neoplastic lesions were observed. Importantly, the rabbits in the BMA transplantation plus hPTH1-34 group showed the highest bone volumes and histological scores of new bone. These data confirmed the feasibility of BMA transplantation combined with hPTH1-34, at least during the experimental period. The observed efficacy may be explained by a synergistic effect from the stimulation of MSC differentiation to osteoblasts with hPTH1-34-mediated suppression of apoptosis in osteoblasts. These results indicate the promising potential for BMA transplantation combined with hPTH1-34 administration in bone necrosis treatment. Longer term experiments are needed to confirm the safety of this therapeutic strategy. PMID:28386485

  1. Preclinical Model To Test Human Papillomavirus Virus (HPV) Capsid Vaccines In Vivo Using Infectious HPV/Cottontail Rabbit Papillomavirus Chimeric Papillomavirus Particles▿

    PubMed Central

    Mejia, Andres F.; Culp, Timothy D.; Cladel, Nancy M.; Balogh, Karla K.; Budgeon, Lynn R.; Buck, Christopher B.; Christensen, Neil D.

    2006-01-01

    A human papillomavirus (HPV) vaccine consisting of virus-like particles (VLPs) was recently approved for human use. It is generally assumed that VLP vaccines protect by inducing type-specific neutralizing antibodies. Preclinical animal models cannot be used to test for protection against HPV infections due to species restriction. We developed a model using chimeric HPV capsid/cottontail rabbit papillomavirus (CRPV) genome particles to permit the direct testing of HPV VLP vaccines in rabbits. Animals vaccinated with CRPV, HPV type 16 (HPV-16), or HPV-11 VLPs were challenged with both homologous (CRPV capsid) and chimeric (HPV-16 capsid) particles. Strong type-specific protection was observed, demonstrating the potential application of this approach. PMID:17005666

  2. Ultrathin, Stretchable, Multiplexing pH Sensor Arrays on Biomedical Devices With Demonstrations on Rabbit and Human Hearts Undergoing Ischemia

    PubMed Central

    Chung, Hyun-Joong; Sulkin, Matthew S.; Kim, Jong-Seon; Goudeseune, Camille; Chao, Hsin-Yun; Song, Joseph W.; Yang, Sang Yoon; Hsu, Yung-Yu; Ghaffari, Roozbeh

    2014-01-01

    Stable pH is an established biomarker of health, relevant to all tissues of the body, including the heart. Clinical monitoring of pH in a practical manner, with high spatiotemporal resolution, is particularly difficult in organs such as the heart due to its soft mechanics, curvilinear geometry, heterogeneous surfaces and continuous, complex rhythmic motion. The results presented here illustrate that advanced strategies in materials assembly and electrochemical growth can yield interconnected arrays of miniaturized IrOx pH sensors encapsulated in thin, low-modulus elastomers to yield conformal monitoring systems capable of non-invasive measurements on the surface of the beating heart. A thirty channel custom data acquisition system enables spatiotemporal pH mapping with a single potentiostat. In-vitro testing reveals super-Nernstian sensitivity with excellent uniformity (69.9 ± 2.2 mV/pH), linear response to temperature (−1.6 mV/°C), and minimal influence of extracellular ions (< 3.5 mV). Device examples include sensor arrays on balloon catheters and on skin-like stretchable membranes. Real-time measurement of pH on the surfaces of explanted rabbit hearts and a donated human heart during protocols of ischemia-reperfusion illustrate some of the capabilities. Envisioned applications range from devices for biological research, to surgical tools and long-term implants. PMID:23868871

  3. Human acid alpha-glucosidase from rabbit milk has therapeutic effect in mice with glycogen storage disease type II.

    PubMed

    Bijvoet, A G; Van Hirtum, H; Kroos, M A; Van de Kamp, E H; Schoneveld, O; Visser, P; Brakenhoff, J P; Weggeman, M; van Corven, E J; Van der Ploeg, A T; Reuser, A J

    1999-11-01

    Pompe's disease or glycogen storage disease type II (GSDII) belongs to the family of inherited lysosomal storage diseases. The underlying deficiency of acid alpha-glucosidase leads in different degrees of severity to glycogen storage in heart, skeletal and smooth muscle. There is currently no treatment for this fatal disease, but the applicability of enzyme replacement therapy is under investigation. For this purpose, recombinant human acid alpha-glucosidase has been produced on an industrial scale in the milk of transgenic rabbits. In this paper we demonstrate the therapeutic effect of this enzyme in our knockout mouse model of GSDII. Full correction of acid alpha-glucosidase deficiency was obtained in all tissues except brain after a single dose of i.v. enzyme administration. Weekly enzyme infusions over a period of 6 months resulted in degradation of lysosomal glycogen in heart, skeletal and smooth muscle. The tissue morphology improved substantially despite the advanced state of disease at the start of treatment. The results have led to the start of a Phase II clinical trial of enzyme replacement therapy in patients.

  4. HIV-specific humoral and cellular immunity in rabbits vaccinated with recombinant human immunodeficiency virus-like gag-env particles

    SciTech Connect

    Haffar, O.K.; Smithgall, M.D.; Moran, P.A.; Travis, B.M.; Zarling, J.M.; Hu, S.L. )

    1991-08-01

    Recombinant human immunodeficiency virus type-1 (HIV-1)-like gag-env particles produced in mammalian cells were inoculated into two New Zealand white rabbits. In parallel, two control rabbits were inoculated with the homologous HIV-1 virions inactivated by ultraviolet light (uv) and psoralen treatments. The humoral and cellular immune responses to HIV-1 were evaluated for both groups of animals. Recombinant particles elicited humoral immunity that was specific for all the viral structural proteins. The antibodies recognized both denatured and nondenatured proteins. Moreover, the sera neutralized the in vitro infectivity of the homologous virus in CEM cells. Importantly, the recombinant particles also generated a T helper response by priming with the HIV proteins. Similar results were observed with inactivated virus immunization. Therefore, the authors results suggest that the recombinant HIV-like particles elicit functional humoral immunity as well as cellular immunity and represent a novel vaccine candidate for AIDS.

  5. Effects of 5-HT receptor agonists on depolarization-induced [3H]-noradrenaline release in rabbit hippocampus and human neocortex.

    PubMed Central

    Allgaier, C.; Warnke, P.; Stangl, A. P.; Feuerstein, T. J.

    1995-01-01

    1. The present study attempted to determine whether noradrenaline (NA) release in rabbit hippocampus and human neocortex is modulated by presynaptic 5-hydroxytryptamine (5-HT) receptors. 2. Slices of rabbit hippocampus and human neocortex, loaded with [3H]-noradrenaline ([3H]-NA) were superfused and the effects of 5-hydroxytryptamine (5-HT) receptor ligands on electrically evoked [3H]-NA release were investigated. 3. In rabbit hippocampus, 5-HT, 5-carboxamidotryptamine (5-CT; 32 microM) and 2-CH3-5-HT (32 microM) increased [3H]-NA release elicited with 360 pulses/3 Hz. Facilitation of transmitter release was not influenced by the 5-HT3 receptor antagonist, tropisetron but was prevented by the alpha 2-adrenoceptor antagonist, rauwolscine. When autoinhibition was avoided by stimulating the tissue with 4 pulses/100 Hz (pseudo-one pulse-(POP) stimulation), 2-CH3-5-HT decreased evoked transmitter release, whereas 5-HT and 5-CT had no effect. Inhibition caused by 2-CH3-5-HT was not affected by tropisetron but counteracted by the alpha 2-adrenoceptor ligands, clonidine and rauwolscine. Inhibition caused by clonidine was diminished in the presence of 5-CT or 2-CH3-5-HT. 4. In human neocortex, [3H]-NA release elicited with 360 pulses/3 Hz was increased by 10 microM 5-HT and 32 microM 5-CT, whereas 2-CH3-5-HT was ineffective. [3H]-NA release evoked with a modified POP stimulation (2 bursts of 4 pulses/100 Hz, 3.5 min apart) was not affected by 2-CH3-5-HT or 5-CT. 5. The present results indicate that 5-HT, 2-CH3-5-HT and 5-CT can act on presynaptic alpha 2-autoreceptors as partial agonists (2-CH3-5-HT; in rabbit hippocampal tissue) or antagonists (5-HT and 5-CT; in tissue of rabbit hippocampus and human neocortex). Furthermore the existence of autoinhibition dictates whether these drugs cause facilitation of release, inhibition or have no effect. PMID:8528558

  6. The effects of ethylene dibromide on semen quality and fertility in the rabbit: evaluation of a model for human seminal characteristics.

    PubMed

    Williams, J; Gladen, B C; Turner, T W; Schrader, S M; Chapin, R E

    1991-05-01

    Mature (12 months old) male New Zealand White rabbits (8-10/group) were dosed subcutaneously with ethylene dibromide (EDB) in corn oil (untreated and vehicle controls, 15, 30, or 45 mg/kg body wt/day for 5 days). Weekly semen samples (for 6 weeks preexposure, during treatment, and 12 weeks postdosing [pd]) were analyzed for sperm concentration, number, morphology, viability, and motion parameters (velocity, linearity, beat cross-frequency, amplitude of lateral head displacement (ALH), and circularity), and semen pH, osmolality, volume, fructose, citric acid, carnitine, protein, and acid phosphatase (AP). Male fertility was assessed preexposure and at 4 and 12 weeks pd by artificial insemination of three females/male/time point with one million motile sperm. The percentage pregnant females, litter size, fetal body weights, and structural development were assessed. In the 45 mg/kg dose group of males there was 30% mortality and liver damage in 43% of the survivors as evidenced by increased levels of serum enzymes. Also in this group, EDB produced significant decreases in sperm velocity, percentage motility, and ALH (up to 25% at various times pd). There were also dose-related decreases in semen pH (up to 2%) and total ejaculate volume (up to 23%, 15 and 30 mg/kg dose groups only). AP activities were significantly elevated (up to 116%) 2 weeks pd in the 45 mg/kg dose group. All other semen parameters evaluated were unaffected. Male fertility and fetal structural development were also unaffected. Of the seven semen parameters perturbed by EDB in humans (Schrader et al., 1988), four were also affected in the rabbit (sperm velocity, percentage motility, pH, and volume), whereas sperm number, viability, and morphology were not. Thus, some of the male reproductive effects of EDB in the human have been modelled in the rabbit, although the rabbit appears not to be as sensitive, since semen parameters were affected only at doses close to the LD50 (55 mg/kg). The present study

  7. Rabbit hematology.

    PubMed

    Marshall, Kemba L

    2008-09-01

    Using laboratory animal medicine as an established resource, companion animal veterinarians have access to many physiologic and basic science studies that we can now merge with our clinical impressions. By working with reference laboratories, companion animal veterinarians are poised to accelerate our knowledge of the normal rabbit rapidly. The aim of this article is to discuss normal hematopoiesis and infectious and metabolic diseases that specifically target the hemolymphatic system. Additionally, photographic representation of cell types is provided.

  8. Blocking effect of methylflavonolamine on human NaV1.5 channels expressed in Xenopus laevis oocytes and on sodium currents in rabbit ventricular myocytes

    PubMed Central

    Fan, Xin-rong; Ma, Ji-hua; Zhang, Pei-hua; Xing, Jun-lian

    2010-01-01

    Aim: To investigate the blocking effects of methylflavonolamine (MFA) on human NaV1.5 channels expressed in Xenopus laevis oocytes and on sodium currents (INa) in rabbit ventricular myocytes. Methods: Human NaV1.5 channels were expressed in Xenopus oocytes and studied using the two-electrode voltage-clamp technique. INa and action potentials in rabbit ventricular myocytes were studied using the whole-cell recording. Results: MFA and lidocaine inhibited human NaV1.5 channels expressed in Xenopus oocytes in a positive rate-dependent and concentration-dependent manner, with IC50 values of 72.61 μmol/L and 145.62 μmol/L, respectively. Both of them markedly shifted the steady-state activation curve of INa toward more positive potentials, shifted the steady-state inactivation curve of INa toward more negative potentials and postponed the recovery of the INa inactivation state. In rabbit ventricular myocytes, MFA inhibited INa with a shift in the steady-state inactivation curve toward more negative potentials, thereby postponing the recovery of the INa inactivation state. This shift was in a positive rate-dependent manner. Under current-clamp mode, MAF significantly decreased action potential amplitude (APA) and maximal depolarization velocity (Vmax) and shortened action potential duration (APD), but did not alter the resting membrane potential (RMP). The demonstrated that the kinetics of sodium channel blockage by MFA resemble those of class I antiarrhythmic agents such as lidocaine. Conclusion: MFA protects the heart against arrhythmias by its blocking effect on sodium channels. PMID:20173760

  9. Selective inhibition of the alternative complement pathway by sCR1[desLHR-A] protects the rabbit isolated heart from human complement-mediated damage.

    PubMed

    Gralinski, M R; Wiater, B C; Assenmacher, A N; Lucchesi, B R

    1996-09-01

    Evidence is presented that treatment with a selective inhibitor of the alternative complement pathway, sCR1[desLHR-A], protects the ex vivo perfused rabbit heart from human complement-mediated injury. Hearts from male New Zealand white rabbits were perfused in the Langendorff mode. After equilibration, normal human plasma was added to the perfusate as a source of complement. Concomitant with the addition of human plasma, vehicle (n = 13), soluble complement receptor type 1 (sCR1) (n = 10), or sCR1[desLHR-A], a truncated version of sCR1 that lacks the C4b binding region (n = 10) was included in the perfusate. Hemodynamic variables were obtained for all groups before (baseline) and after the addition of human plasma. Compared to vehicle-treated hearts, variables recorded during perfusion with human plasma including coronary perfusion pressure, left ventricular developed pressure, and left ventricular end diastolic pressure, along with a reduction of creatine kinase efflux, were improved in hearts perfused with either complement inhibitor. In addition, in vitro hemolysis assays were utilized to discriminate between the classical and alternative pathways. The addition of sCR1 to human serum prevented both the classical and alternative pathway-mediated hemolysis while sCR1[desLHR-A] prevented only the alternative pathway-mediated lysis. This study indicates that deletion of the C4b-binding site from sCR1 results in a new pharmacological moiety, sCR1[desLHR-A], that primarily inhibits the alternative pathway of human complement.

  10. 2-/sup 14/C-1-Allyl-3,5-diethyl-6-chlorouracil I: Synthesis, absorption in human skin, excretion, distribution, and metabolism in rats and rabbits

    SciTech Connect

    Kaul, R.; Hempel, B.; Kiefer, G.

    1982-08-01

    With /sup 14/C-potassium cyanate as the starting material, 2-/sup 14/C-1-allyl-3,5-diethyl-6-chlorouracil was synthesized for in vitro and in vivo absorption studies in human skin and for metabolic studies in rats and rabbits. The radioactivity in the horny layer, epidermis, and dermis of the human skin was determined after different intervals of time, and the radioactivity excreted in the urine was measured by collecting samples for 5 days from a patient and also under occlusion conditions. Almost 90% of the radioactivity remained on the surface and approximately 6.28% penetrated and was systemically absorbed. Over a 5-day period, a total of 3.25% was excreted. Almost 3% was systemically absorbed and cumulated in the system. After intraperitoneal application in male and female rats, most of the radioactivity was excreted in the feces and urine, with female rats excreting more in the urine than male rats. The radioactivity rose in the organs in the first 3 hr and then decreased. At the end of 144 hr, no appreciable radioactivity could be found in the organs and tissues, except in the carcass where the cumulation was maximum (1%). After intravenous injection in rabbits, most of the radioactivity (80%) was excreted in the urine and only 4% in the feces. At the end of 96 hr, approximately 3% was cumulated in the body. The drug was quantitatively metabolized in both rats and rabbits: Metabolite 1 (70-85%), Metabolite 2 (10-15%), Metabolite 3 (5-10%), and Metabolite 4 (0.3%).

  11. The cottontail rabbits of Virginia

    USGS Publications Warehouse

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

    1945-01-01

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

  12. Serological studies of an acid-labile O-polysaccharide of Proteus vulgaris OX19 lipopolysaccharide using human and rabbit antibodies.

    PubMed

    Kaca, W; Swierzko, A S; Ziolkowski, A; Amano, K; Senchenkova, S N; Knirel, Y A

    1998-01-01

    In a Weil-Felix test, sera from patients infected with Rickettsia sp. agglutinate Proteus OX types of bacteria and Proteus lipopolysaccharide (LPS) are responsible for the cross-reaction. Data on the character of LPS of one of the OX group strains, Proteus vulgaris OX19, are contradictory, and it remained unclear whether it has an O-polysaccharide (OPS) and is thus LPS of the smooth type (S) or not (rough-type LPS). Our studies showed that P. vulgaris OX19 (strain PZH-24) produces a smooth-type LPS that contains a long-chain OPS, but it undergoes depolymerization during mild acid hydrolysis conventionally used for LPS delipidation and loses the serological activity. An elucidation of the complete structure of OPS demonstrated the presence of a glycosyl phosphate linkage responsible for the acid-lability of the polysaccharide chain. In ELISA, both IgM type antibodies in a Weil-Felix test with human anti-Rickettsia typhi sera and rabbit anti-P. vulgaris OX19 antibodies reacted with OPS. Rabbit antibodies did not inhibit the cross-reaction with human antibodies and thus bind to different epitopes.

  13. RABBIT POX

    PubMed Central

    Rosahn, Paul D.; Hu, Ch'uan-K'uei

    1935-01-01

    Observations on an epidemic of rabbit pox occurring in an isolated animal room during the winter of 1933–34 are reported. The clinical manifestations, consisting of a generalized papular eruption involving the skin and mucous membranes, together with blepharitis, ophthalmia, nasal discharge and lymphadenopathy were essentially similar to those noted in a pox epidemic of the previous year. This was true in general also of the pathological findings except that vacuolization, local necrosis and vesicle formation were seen in the epidermis, while in the previous year the microscopic pathology in the skin was confined to the corium. Evidence was presented indicating that the infection can be transmitted through the medium of a personal carrier, and that transmission in this manner can occur during the incubation period or before a definite diagnosis is possible. The findings also demonstrated that the etiological agents responsible for the disease reported here and that of the previous year were immunologically related, and that the immunity in recovered animals effectively persisted during the entire period for which data are available, 9 to 12 months. It appeared also that young animals suckling an immune doe were more refractory to the development of the lesions of rabbit pox than were the young of susceptible does. PMID:19870418

  14. Plasma High-Mannose and Complex/Hybrid N-Glycans Are Associated with Hypercholesterolemia in Humans and Rabbits

    PubMed Central

    Bai, Liang; Li, Qianwei; Li, Lingmei; Lin, Yan; Zhao, Sihai; Wang, Weirong; Wang, Rong; Li, Yongqin; Yuan, Jiangbei; Wang, Chengjian; Wang, Zhongfu; Fan, Jianglin; Liu, Enqi

    2016-01-01

    N-glycans play important roles in various pathophysiological processes and can be used as clinical diagnosis markers. However, plasma N-glycans change and their pathophysiological significance in the setting of hypercholesterolemia, a major risk factor for atherosclerosis, is unknown. Here, we collected plasma from both hypercholesterolemic patients and cholesterol-fed hypercholesterolemic rabbits, and determined the changes in the whole-plasma N-glycan profile by electrospray ionization mass spectrometry. We found that both the hypercholesterolemic patients and rabbits showed a dramatic change in their plasma glycan profile. Compared with healthy subjects, the hypercholesterolemic patients exhibited higher plasma levels of a cluster of high-mannose and complex/hybrid N-glycans (mainly including undecorated or sialylated glycans), whereas only a few fucosylated or fucosylated and sialylated N-glycans were increased. Additionally, cholesterol-fed hypercholesterolemic rabbits also displayed increased plasma levels of high-mannose in addition to high complex/hybrid N-glycan levels. The whole-plasma glycan profiles revealed that the plasma N-glycan levels were correlated with the plasma cholesterol levels, implying that N-glycans may be a target for treatment of hypercholesterolemia. PMID:26999365

  15. Risk of zoonotic transmission of HEV from rabbits.

    PubMed

    Lhomme, Sébastien; Dubois, Martine; Abravanel, Florence; Top, Sokunthea; Bertagnoli, Stéphane; Guerin, Jean-Luc; Izopet, Jacques

    2013-10-01

    Hepatitis E virus strains from rabbits indicate that these mammals may be a reservoir for HEVs that cause infection in humans. Further issues remain to be clarified, including whether the genotype of rabbit HEV differs from human and swine HEV genotype 3 and whether rabbit HEV can infect human and other animals. HEV was found in farmed rabbits in several geographic areas of China, in USA and more recently in France. The prevalence of antibodies against HEV was 36%, 57% and 55% in rabbits from Virginia (USA), Gansu Province and Beijing (China), respectively. HEV RNA was detected in 16.5% of serum samples from farmed rabbits in Virginia, 7.5% in Gansu Province and 7.0% in Beijing. HEV RNA was detected in 7% of bile samples from farmed rabbits and in 23% of liver samples from wild rabbits in France. The full-length genomic sequences analysis indicates that all the rabbit strains belong to the same clade. Nucleotide sequences were 72.2-78.2% identical to HEV genotypes 1-4. Comparison with HEV sequences of human strains circulating in France and reference sequences identified a human strain closely related to rabbit HEV. A 93-nucleotide insertion in the X domain of the ORF1 of the human strain and in all the rabbit HEV strains was found. Moreover, the ability of rabbit HEV to cause cross-species infection in a pig model has recently been demonstrated. Rabbit HEV can replicate efficiently in human cell lines. Collectively, these data support the possibility of zoonotic transmission of HEV from rabbits.

  16. Seroprevalence of toxoplasma gondii infection in domestic rabbits in Durango State, Mexico

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Toxoplasma gondii infection in rabbits is of public health importance because rabbit meat is consumed by humans, and rabbits are preyed upon by cats that then shed environmentally resistant oocysts. Antibodies to T. gondii were determined in 429 domestic rabbits in Durango State, Mexico using the mo...

  17. Optimization and validation of RP-HPLC-UV method with solid-phase extraction for determination of buparvaquone in human and rabbit plasma: application to pharmacokinetic study.

    PubMed

    Venkatesh, Gantala; Majid, M I A; Ramanathan, S; Mansor, S M; Nair, N K; Croft, Simon L; Navaratnam, V

    2008-05-01

    A simple, sensitive and specific reversed-phase high-performance liquid chromatographic method with UV detection at 251 nm was developed for quantitation of buparvaquone (BPQ) in human and rabbit plasma. The method utilizes 250 microL of plasma and sample preparation involves protein precipitation followed by solid-phase extraction. The method was validated on a C18 column with mobile phase consisting of ammonium acetate buffer (0.02 m, pH 3.0) and acetonitrile in the ratio of 18:82 (v/v) at a flow rate of 1.1 mL/min. The calibration curves were linear (correlation coefficient>or=0.998) in the selected range. The method is specific and sensitive with limit of quantitation of 50 ng/mL for BPQ. The validated method was found to be accurate and precise in the working calibration range. Stability studies were carried out at different storage conditions and BPQ was found to be stable. Partial validation studies were carried out using rabbit plasma and intra- and inter-day precision and accuracy were within 7%. This method is simple, reliable and can be routinely used for preclinical pharmacokinetic studies for BPQ.

  18. Hydrocaffeic and p-coumaric acids, natural phenolic compounds, inhibit UV-B damage in WKD human conjunctival cells in vitro and rabbit eye in vivo.

    PubMed

    Larrosa, Mar; Lodovici, Maura; Morbidelli, Lucia; Dolara, Piero

    2008-10-01

    This paper studied the effect on UV-B ocular damage of 10microM hydrocaffeic acid (HCAF) alone and as a mixture (MIX) (5 microM HCAF+5 microM p-coumaric acid). Since ocular UV-B damage is mediated by reactive oxygen species, the aim was to test if HCAF and MIX could reduce oxidation damage in human conjunctival cells (WKD) in vitro and in cornea and sclera of rabbits in vivo. After UVB irradiation (44 J/m(2)) of WKD cells, 8-oxodG levels in DNA were markedly increased and this effect was attenuated by HCAF and MIX. Rabbit eyes were treated by application of HCAF and MIX drops before UV-B exposure (79 J/m(2)). Corneal and scleral DNA oxidation damage, xanthine-oxidase (XO) activity and malondialdehyde levels (MDA) in corneal tissue and prostaglandin E(2) (PGE(2)) in the aqueous humour were reduced by HCAF alone and in combination with p-coumaric acid, showing their potential as a topical treatment against UV-B damage.

  19. A rabbit vaginal cell-derived antimicrobial peptide, RVFHbαP, blocks lipopolysaccharide-mediated inflammation in human vaginal cells in vitro.

    PubMed

    Patgaonkar, Mandar S; Sathe, Ameya; Selvaakumar, C; Reddy, K V R

    2011-10-01

    Antimicrobial peptides (AMPs) constitute a phylogenetically ancient form of innate immunity that provides host defense at various mucosal surfaces, including the vagina. Recently, we have identified one such AMP, rabbit vaginal fluid hemoglobin alpha peptide (RVFHbαP), from the vaginal lavage of rabbits (Oryctolagus cuniculus). The recent demonstration of a protective role of this peptide in erythrocytes and vaginal cells led us to investigate (i) the lipopolysaccharide (LPS) interactive domain in RVFHbαP and (ii) whether RVFHbαP of rabbit origin modulates the cellular immune responses of another species (humans) in vitro. HeLa-S3, a human vaginal epithelial cell line (hVEC), was exposed to LPS alone (10 μg/ml for 6 h), or LPS-induced cells were treated with RVFHbαP (70.45 μM for 1 h) and cultured for 24 h, and the results obtained were compared with the medium control. We show here that RVFHbαP exerts an anti-inflammatory activity in hVECs, as suggested by the prevention of LPS-induced production of extracellular (supernatant) and intracellular (lysate) levels of cytokines (interleukin 6 [IL-6] and IL-1α) and chemokines (IL-8 and monocyte chemoattractant protein 1 [MCP-1]). The demonstration of Toll-like receptor 4 (TLR4) and NF-κB expression in hVECs and the observations of RVFHbαP suppression of human β-defensin-1 (hBD1) mRNA expression further support the hypothesis of a genomic activity of RVFHbαP. Confocal microscopy and flow cytometry results demonstrate that RVFHbαP inhibits LPS-induced phagocytosis of Escherichia coli by macrophages. The chemotaxis studies performed using the Boyden chamber Transwell method showed the increased migration of U937 cells when supernatants of LPS-induced hVECs were used, and this effect was inhibited by RVFHbαP. In conclusion, our study proposes a novel explanation for the protective role of RVFHbαP in inflammation-associated infections, which not only may provide the new cellular targets for the screening of

  20. European Concerted Action on Anticoagulation. A multicentre calibration study of WHO international reference preparations for thromboplastin, rabbit (RBT/90) and human (rTF/95)

    PubMed Central

    Poller, L; Keown, M; Chauhan, N; van den Besselaar, A M H P; Tripodi, A; Shiach, C; Jespersen, J

    2005-01-01

    A 10 centre calibration was performed after six years to determine the international sensitivity index (ISI) of rTF/95 relative to RBT/90, and to assess any international normalised ratio (INR) bias compared with the original multicentre calibration. After exclusion of one outlying centre, the follow up calibration gave a mean ISI for rTF/95 of 0.99, which although a small difference, is significantly greater than the mean ISI of 0.94 obtained previously. The change in ISI for international reference preparation (IRP) rTF/95 relative to RBT/90 would lead to a slight bias in INR for human compared with rabbit thromboplastins. At a theoretical INR of 3.0, the INR bias is 6.0%, and this is below the accepted 10% level of clinical relevance. Ongoing stability monitoring of World Health Organisation thromboplastin IRP is advised. PMID:15917425

  1. Theoretical analysis of the neuraminidase epitope of the Mexican A H1N1 influenza strain, and experimental studies on its interaction with rabbit and human hosts.

    PubMed

    Loyola, Paola Kinara Reyes; Campos-Rodríguez, R; Bello, Martiniano; Rojas-Hernández, S; Zimic, Mirko; Quiliano, Miguel; Briz, Verónica; Muñoz-Fernández, M Angeles; Tolentino-López, Luis; Correa-Basurto, Jose

    2013-05-01

    The neuraminidase (NA) epitope from the Mexican AH1N1 influenza virus was identified by using sequences registered at the GenBank during the peak of a pandemic (from April 2009 to October 2010). First, NA protein sequences were submitted for multiple alignment analysis, and their three-dimensional models (3-D) were then built by using homology modeling. The most common sequence (denominated wild-type) and its mutants were submitted to linear and nonlinear epitope predictors, which included the major histocompatibility complex type II (MHC II) and B-cell peptides. The epitope prediction was in accordance with evolutionary behavior and some protein structural properties. The latter included a low NA mutation rate, NA 3-D surface exposure, and the presence of high hindrance side chain residues. After selecting the epitope, docking studies and molecular dynamics (MD) simulations were used to explore interactions between the epitope and MHC II. Afterward, several experimental assays were performed to validate the theoretical study by using antibodies from humans (infected by pandemic H1N1) and rabbits (epitope vaccination). The results show 119 complete sequences that were grouped into 28 protein sequences according to their identity (one wild-type and 27 representative mutants (1-5 mutations)). The predictors yielded several epitopes, with the best fit being the one located in the C-terminal region. Theoretical methods demonstrated that the selected epitope reached the P4, P6, P7, and P9 pockets of MHC II, whereas the experimental evidence indicates that the epitope is recognized by human antibodies and also by rabbit antibodies immunized with the peptide.

  2. Substrate specificity of the electrogenic sodium/bicarbonate cotransporter NBCe1-A (SLC4A4, variant A) from humans and rabbits.

    PubMed

    Lee, Seong-Ki; Boron, Walter F; Parker, Mark D

    2013-04-01

    In the basolateral membrane of proximal-tubule cells, NBCe1-A (SLC4A4, variant A), operating with an apparent Na(+):HCO(3)(-) stoichiometry of 1:3, contributes to the reclamation of HCO(3)(-) from the glomerular filtrate, thereby preventing whole body acidosis. Others have reported that NBCe1-like activity in human, rabbit, and rat renal preparations is substantially influenced by lithium, sulfite, oxalate, and harmaline. These data were taken as evidence for the presence of distinct Na(+) and CO(3)(2-) binding sites in NBCe1-A, favoring a model of 1 Na(+):1 HCO(3)(-):1 CO(3)(2-). Here, we reexamine these findings by expressing human or rabbit NBCe1-A clones in Xenopus oocytes. In oocytes, NBCe1-A exhibits a 1:2 stoichiometry and could operate in one of five thermodynamically equivalent transport modes: 1) cotransport of Na(+) + 2 HCO(3)(-), 2) cotransport of Na(+) + CO(3)(2-), 3) transport of NaCO(3)(-), 4) exchange of Na(+) + HCO(3)(-) for H(+), or 5) HCO(3)(-)-activated exchange of Na(+) for 2 H(+). In contrast to the behavior of NBCe1-like activity in renal preparations, we find that cloned NBCe1-A is only slightly stimulated by Li(+), not at all influenced by sulfite or oxalate, and only weakly inhibited by harmaline. These negative data do not uniquely support any of the five models above. In addition, we find that NBCe1-A mediates a small amount of Na(+)-independent NO(3)(-) transport and that NBCe1-A is somewhat inhibited by extracellular benzamil. We suggest that the features of NBCe1-like activity in renal preparations are influenced by yet-to-be-identified renal factors. Thus the actual ionic substrates of NBCe1 remain to be identified.

  3. Viral infections of rabbits.

    PubMed

    Kerr, Peter J; Donnelly, Thomas M

    2013-05-01

    Viral diseases of rabbits have been used historically to study oncogenesis (e.g. rabbit fibroma virus, cottontail rabbit papillomavirus) and biologically to control feral rabbit populations (e.g. myxoma virus). However, clinicians seeing pet rabbits in North America infrequently encounter viral diseases although myxomatosis may be seen occasionally. The situation is different in Europe and Australia, where myxomatosis and rabbit hemorrhagic disease are endemic. Advances in epidemiology and virology have led to detection of other lapine viruses that are now recognized as agents of emerging infectious diseases. Rabbit caliciviruses, related to rabbit hemorrhagic disease, are generally avirulent, but lethal variants are being identified in Europe and North America. Enteric viruses including lapine rotavirus, rabbit enteric coronavirus and rabbit astrovirus are being acknowledged as contributors to the multifactorial enteritis complex of juvenile rabbits. Three avirulent leporid herpesviruses are found in domestic rabbits. A fourth highly pathogenic virus designated leporid herpesvirus 4 has been described in Canada and Alaska. This review considers viruses affecting rabbits by their clinical significance. Viruses of major and minor clinical significance are described, and viruses of laboratory significance are mentioned.

  4. Mapping superficial lymphatic territories in the rabbit.

    PubMed

    Soto-Miranda, Miguel A; Suami, Hiroo; Chang, David W

    2013-06-01

    Little is known about the anatomy of the lymphatic system in the rabbit with regard to relationships between the lymphatic vessel and lymph node. According to our previous studies in human cadavers and canines, the superficial lymphatic system could be divided into lymphatic territories. The aim of this study was to completely map the superficial lymphatic system in the rabbit. We used our microinjection technique and histological analysis for dissecting studies and recently developed indocyanine green (ICG) fluorescent lymphography for demonstrating dynamic lymph flow in living rabbits. Real-time ICG fluorescent lymphography was performed in two living New Zealand White rabbits, and direct dye microinjection of the lymphatic vessels was performed in eight dead rabbits. To assess the relationships between the vascular and lymphatic systems in rabbits, we performed radiocontrast injection into arteries in two dead rabbits prior to the lymphatic injection. The ICG fluorescent lymphography revealed eight lymphatic territories in the preauricular, submandibular, root of the lateral neck, axillary, lumbar, inguinal, root of the tail, and popliteal regions. We injected blue acrylic dye into every lymphatic vessel 0.1 mm in diameter or larger. We then dissected and chased the stained lymphatic vessels proximally until the vessels connected to the first tier lymph node. This procedure was repeated throughout the body until all the relationships between the lymphatic vessels and lymph nodes were defined. The lymphatic system of the rabbit could be defined as eight lymphatic territories, each with its own lymphatic vessels and lymph node.

  5. Novel Interaction Mechanism of a Domain Antibody-based Inhibitor of Human Vascular Endothelial Growth Factor with Greater Potency than Ranibizumab and Bevacizumab and Improved Capacity over Aflibercept*

    PubMed Central

    Walker, Adam; Chung, Chun-Wa; Neu, Margarete; Burman, Manish; Batuwangala, Thil; Jones, Gavin; Tang, Chi-Man; Steward, Michael; Mullin, Michael; Tournier, Nadia; Lewis, Alan; Korczynska, Justyna; Chung, Vicky; Catchpole, Ian

    2016-01-01

    A potent VEGF inhibitor with novel antibody architecture and antigen binding mode has been developed. The molecule, hereafter referred to as VEGF dual dAb (domain antibody), was evaluated in vitro for binding to VEGF and for potency in VEGF-driven models and compared with other anti-VEGF biologics that have been used in ocular anti-angiogenic therapeutic regimes. VEGF dual dAb is more potent than bevacizumab and ranibizumab for VEGF binding, inhibition of VEGF receptor binding assays (RBAs), and VEGF-driven in vitro models of angiogenesis and displays comparable inhibition to aflibercept (Eylea). VEGF dual dAb is dimeric, and each monomer contains two distinct anti-VEGF domain antibodies attached via linkers to a human IgG1 Fc domain. Mechanistically, the enhanced in vitro potency of VEGF dual dAb, in comparison to other anti-VEGF biologics, can be explained by increased binding stoichiometry. A consistent model of the target engagement has been built based on the x-ray complexes of each of the two isolated domain antibodies with the VEGF antigen. PMID:26728464

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

    PubMed

    Robinson, G; Chalmers, R M

    2010-12-01

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

  7. Effects of Escherichia Coli-derived Recombinant Human Bone Morphogenetic Protein-2 Loaded Porous Hydroxyaptite-based Ceramics on Calvarial Defect in Rabbits

    PubMed Central

    Kim, Shin-Young; Lee, Youngkyun; Seo, Seung-Jun; Lim, Jae-Hong

    2017-01-01

    Background Recombinant human bone morphogenetic proteins (rhBMPs) have been widely used in regenerative therapies to promote bone formation. The production of rhBMPs using bacterial systems such as Escherichia coli (E. coli) is estimated to facilitate clinical applications by lowering the cost without compromising biological activity. In clinical practice, rhBMP-2 and osteoconductive carriers (e.g., hydroxyapatite [HA] and bovine bone xenograft) are used together. This study examined the effect of E. coli-derived rhBMP-2 combined with porous HA-based ceramics on calvarial defect in rabbits. Methods Six adult male New Zealand white rabbits were used in this study. The experimental groups were divided into the following 4 groups: untreated (NC), bovine bone graft (BO), porous HA (HA) and porous HA with rhBMP-2 (HA-BMP). Four transosseous defects of 8 mm in diameter were prepared using stainless steel trephine bur in the frontal and parietal bones. Histological and histomorphometric analyses at 4 weeks after surgery revealed significant new bone formation by porous HA alone. Results HA-BMP showed significantly higher degree of bone formation compared with BO and HA group (P<0.05). The average new bone formation % (new bone area per total defect area) of NC, BO, HA, and HA-BMP at 4-week after surgery were 12.65±5.89%, 29.63±6.99%, 28.86±6.17% and 49.56±8.23%, respectively. However, there was no statistical difference in the bone formation between HA and BO groups. Conclusions HA-BMP promoted more bone formation than NC, BO and HA alone. Thus, using E. coli-derived rhBMP-2 combined with porous HA-based ceramics can promote new bone formation. PMID:28326298

  8. Cytochrome P450 down-regulation by serum from humans with a viral infection and from rabbits with an inflammatory reaction.

    PubMed

    Bleau, A M; Fradette, C; El-Kadi, A O; Côté, M C; du Souich, P

    2001-07-01

    Serum from humans with an upper respiratory viral infection (HS(URVI)) and from rabbits with a turpentine-induced acute inflammatory reaction (RS(TIAR)) reduces the activity of hepatic cytochrome P450 (P450) following 4 h of incubation. The aim of the present study was to assess the effect of HS(URVI) and RS(TIAR) on P450 activity and expression following 24 h of incubation with hepatocytes from control (H(CONT)) and rabbits with a TIAR (H(INFLA)). RS(TIAR) incubated with H(CONT) for 24 h reduced P450 content and activity, and CYP3A6 by 45%, without changing CYP1A1 and 1A2; when incubated with H(INFLA), RS(TIAR) decreased P450 content and activity without affecting CYP1A1 or 1A2. HS(URVI) incubated for 4 h with H(CONT) decreased P450 activity without affecting the amounts of CYP1A1, 1A2, or 3A6, although when incubated for 24 h, P450 activity and CYP3A6 amount decreased. HS(URVI) incubated with H(INFLA) for 4 h reduced P450 content and activity, and incubated for 24 h reduced activity, P450 content, and amount of CYP1A1 and 1A2 proteins. The present study demonstrates that 1) the effect of RS(TIAR) and HS(URVI) depends upon the susceptibility of the hepatocyte, i.e., H(CONT) or primed H(INFLA); 2) P450 down-regulation is preceded by a decrease in P450 activity; 3) the nature of the inflammatory reaction determines the repercussions on P450 activity and expression; and 4) CYP3A6 is more vulnerable than CYP1A1 and 1A2 to the down-regulation provoked by an inflammatory challenge.

  9. Human RPE Stem Cells Grown into Polarized RPE Monolayers on a Polyester Matrix Are Maintained after Grafting into Rabbit Subretinal Space

    PubMed Central

    Stanzel, Boris V.; Liu, Zengping; Somboonthanakij, Sudawadee; Wongsawad, Warapat; Brinken, Ralf; Eter, Nicole; Corneo, Barbara; Holz, Frank G.; Temple, Sally; Stern, Jeffrey H.; Blenkinsop, Timothy A.

    2014-01-01

    Summary Transplantation of the retinal pigment epithelium (RPE) is being developed as a cell-replacement therapy for age-related macular degeneration. Human embryonic stem cell (hESC) and induced pluripotent stem cell (iPSC)-derived RPE are currently translating toward clinic. We introduce the adult human RPE stem cell (hRPESC) as an alternative RPE source. Polarized monolayers of adult hRPESC-derived RPE grown on polyester (PET) membranes had near-native characteristics. Trephined pieces of RPE monolayers on PET were transplanted subretinally in the rabbit, a large-eyed animal model. After 4 days, retinal edema was observed above the implant, detected by spectral domain optical coherence tomography (SD-OCT) and fundoscopy. At 1 week, retinal atrophy overlying the fetal or adult transplant was observed, remaining stable thereafter. Histology obtained 4 weeks after implantation confirmed a continuous polarized human RPE monolayer on PET. Taken together, the xeno-RPE survived with retained characteristics in the subretinal space. These experiments support that adult hRPESC-derived RPE are a potential source for transplantation therapies. PMID:24511471

  10. Cloning, Characteristics, and Functional Analysis of Rabbit NADPH Oxidase 5

    PubMed Central

    Chen, Feng; Yin, Caiyong; Dimitropoulou, Christiana; Fulton, David J. R.

    2016-01-01

    Background: Nox5 was the last member of the Nox enzyme family to be identified. Functionally distinct from the other Nox isoforms, our understanding of its physiological significance has been hampered by the absence of Nox5 in mouse and rat genomes. Nox5 is present in the genomes of other species such as the rabbit that have broad utility as models of cardiovascular disease. However, the mRNA sequence, characteristics, and functional analysis of rabbit Nox5 has not been fully defined and were the goals of the current study. Methods: Rabbit Nox5 was amplified from rabbit tissue, cloned, and sequenced. COS-7 cells were employed for expression and functional analysis via Western blotting and measurements of superoxide. We designed and synthesized miRNAs selectively targeting rabbit Nox5. The nucleotide and amino acid sequences of rabbit Nox5 were aligned with those of putative rabbit isoforms (X1, X2, X3, and X4). A phylogenetic tree was generated based on the mRNA sequence for Nox5 from rabbit and other species. Results: Sequence alignment revealed that the identified rabbit Nox5 was highly conserved with the predicted sequence of rabbit Nox5. Cell based experiments reveal that rabbit Nox5 was robustly expressed and produced superoxide at rest and in a calcium and PMA-dependent manner that was susceptible to superoxide dismutase and the flavoprotein inhibitor, DPI. miRNA-1 was shown to be most effective in down-regulating the expression of rabbit Nox5. Phylogenetic analysis revealed a close relationship between rabbit and armadillo Nox5. Rabbit Nox5 was relatively closely related to human Nox5, but lies in a distinct cluster. Conclusion: Our study establishes the suitability of the rabbit as a model organism to further our understanding of the role of Nox5 in cardiovascular and other diseases and provides new information on the genetic relationship of Nox5 genes in different species. PMID:27486403

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

    PubMed Central

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

    1987-01-01

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

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

    PubMed

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

    2012-12-01

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

  13. AGIA Tag System Based on a High Affinity Rabbit Monoclonal Antibody against Human Dopamine Receptor D1 for Protein Analysis

    PubMed Central

    Yano, Tomoya; Takeda, Hiroyuki; Uematsu, Atsushi; Yamanaka, Satoshi; Nomura, Shunsuke; Nemoto, Keiichirou; Iwasaki, Takahiro; Takahashi, Hirotaka; Sawasaki, Tatsuya

    2016-01-01

    Polypeptide tag technology is widely used for protein detection and affinity purification. It consists of two fundamental elements: a peptide sequence and a binder which specifically binds to the peptide tag. In many tag systems, antibodies have been used as binder due to their high affinity and specificity. Recently, we obtained clone Ra48, a high-affinity rabbit monoclonal antibody (mAb) against dopamine receptor D1 (DRD1). Here, we report a novel tag system composed of Ra48 antibody and its epitope sequence. Using a deletion assay, we identified EEAAGIARP in the C-terminal region of DRD1 as the minimal epitope of Ra48 mAb, and we named this sequence the “AGIA” tag, based on its central sequence. The tag sequence does not include the four amino acids, Ser, Thr, Tyr, or Lys, which are susceptible to post-translational modification. We demonstrated performance of this new tag system in biochemical and cell biology applications. SPR analysis demonstrated that the affinity of the Ra48 mAb to the AGIA tag was 4.90 × 10−9 M. AGIA tag showed remarkably high sensitivity and specificity in immunoblotting. A number of AGIA-fused proteins overexpressed in animal and plant cells were detected by anti-AGIA antibody in immunoblotting and immunostaining with low background, and were immunoprecipitated efficiently. Furthermore, a single amino acid substitution of the second Glu to Asp (AGIA/E2D) enabled competitive dissociation of AGIA/E2D-tagged protein by adding wild-type AGIA peptide. It enabled one-step purification of AGIA/E2D-tagged recombinant proteins by peptide competition under physiological conditions. The sensitivity and specificity of the AGIA system makes it suitable for use in multiple methods for protein analysis. PMID:27271343

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

    PubMed

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

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

    SciTech Connect

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

    2016-01-28

    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.

  16. Three-dimensional bioprinting of multilayered constructs containing human mesenchymal stromal cells for osteochondral tissue regeneration in the rabbit knee joint.

    PubMed

    Shim, Jin-Hyung; Jang, Ki-Mo; Hahn, Sei Kwang; Park, Ju Young; Jung, Hyuntae; Oh, Kyunghoon; Park, Kyeng Min; Yeom, Junseok; Park, Sun Hwa; Kim, Sung Won; Wang, Joon Ho; Kim, Kimoon; Cho, Dong-Woo

    2016-02-04

    The use of cell-rich hydrogels for three-dimensional (3D) cell culture has shown great potential for a variety of biomedical applications. However, the fabrication of appropriate constructs has been challenging. In this study, we describe a 3D printing process for the preparation of a multilayered 3D construct containing human mesenchymal stromal cells with a hydrogel comprised of atelocollagen and supramolecular hyaluronic acid (HA). This construct showed outstanding regenerative ability for the reconstruction of an osteochondral tissue in the knee joints of rabbits. We found that the use of a mechanically stable, host-guest chemistry-based hydrogel was essential and allowed two different types of extracellular matrix (ECM) hydrogels to be easily printed and stacked into one multilayered construct without requiring the use of potentially harmful chemical reagents or physical stimuli for post-crosslinking. To the best of our knowledge, this is the first study to validate the potential of a 3D printed multilayered construct consisting of two different ECM materials (atelocollagen and HA) for heterogeneous tissue regeneration using an in vivo animal model. We believe that this 3D printing-based platform technology can be effectively exploited for regeneration of various heterogeneous tissues as well as osteochondral tissue.

  17. Efficacy of CMX001 as a Prophylactic and Presymptomatic Antiviral Agent in New Zealand White Rabbits Infected with Rabbitpox Virus, a Model for Orthopoxvirus Infections of Humans

    PubMed Central

    Rice, Amanda D.; Adams, Mathew M.; Lampert, Bernhard; Foster, Scott; Lanier, Randall; Robertson, Alice; Painter, George; Moyer, Richard W.

    2011-01-01

    CMX001, a lipophilic nucleotide analog formed by covalently linking 3-(hexdecyloxy)propan-1-ol to cidofovir (CDV), is being developed as a treatment for smallpox. CMX001 has dramatically increased potency versus CDV against all dsDNA viruses and, in contrast to CDV, is orally available and has shown no evidence of nephrotoxicity in healthy volunteers or severely ill transplant patients to date. Although smallpox has been eliminated from the environment, treatments are urgently being sought due to the risk of smallpox being used as a bioterrorism agent and for monkeypox virus, a zoonotic disease of Africa, and adverse reactions to smallpox virus vaccinations. In the absence of human cases of smallpox, new treatments must be tested for efficacy in animal models. Here we first review and discuss the rabbitpox virus (RPV) infection of New Zealand White rabbits as a model for smallpox to test the efficacy of CMX001 as a prophylactic and early disease antiviral. Our results should also be applicable to monkeypox virus infections and for treatment of adverse reactions to smallpox vaccination. PMID:21369346

  18. Molecular characterization of Rickettsia rickettsii isolated from human clinical samples and from the rabbit tick Haemaphysalis leporispalustris collected at different geographic zones in Costa Rica.

    PubMed

    Hun, Laya; Cortés, Ximena; Taylor, Lizeth

    2008-12-01

    Five strains of spotted fever group (SFG) rickettsiae previously isolated from human clinical cases and from the tick Haemaphysalis leporispalustris were used for molecular characterization in this study to establish their genetic relationship compared with the prototype Rickettsia rickettsii strain Sheila Smith. Samples were tested by polymerase chain reaction (PCR) targeting the rickettsial genes gtlA, ompA, and ompB. PCR products of the latter two genes were DNA sequenced and compared with available sequences in GenBank. The ompA partial sequences of the five Costa Rican isolates showed 100% identity to several R. rickettsii sequences available in GenBank, including the sequence of the virulent reference strain Sheila Smith, whereas the ompB partial sequences of the five Costa Rican isolates showed 99.8-100% identity to R. rickettsii sequences from GenBank. This study showed the first molecular detection of R. rickettsii isolates from Rocky Mountain Spotted Fever patients and from the rabbit tick H. leporispalustris in different geographical zones in Costa Rica.

  19. A murine monoclonal anti-idiotypic antibody detects a common idiotope on human, mouse and rabbit antibodies to allergen Lol p IV.

    PubMed

    Zhou, E M; Dzuba-Fischer, J M; Rector, E S; Sehon, A H; Kisil, F T

    1991-09-01

    A syngeneic mouse monoclonal anti-idiotypic antibody (anti-Id), designated as B1/1, was generated against a monoclonal antibody (MoAb 91) specific for Ryegrass pollen allergen Lol p IV. This anti-Id recognized an idiotope (Id) that was also present on other monoclonal antibodies with the same specificity as MoAb 91. Observations that (i) the anti-Id inhibited the binding of MoAb 91 to Lol p IV and (ii) the Id-anti-Id interaction could be inhibited by Lol p IV indicated that the Id was located within or near the antigen combining site. These properties served to characterize B1/1 as an internal image anti-Id. Evidence that an immune response in different species to Lol p IV elicits the formation of antibodies which express a common Id was provided by the observations that (i) the Id-anti-Id interactions could be inhibited by mouse, human and rabbit antisera to Lol p IV and (ii) the binding of these antisera to Lol p IV could be inhibited by the anti-Id. Interestingly, the internal image anti-Id B1/1 also recognized an Id on a monoclonal antibody which was directed to an epitope of Lol p IV, different from that recognized by MoAb 91.

  20. Enterotoxin Gene Cluster-Encoded SEI and SElN from Staphylococcus aureus Isolates are Crucial for the Induction of Human Blood Cell Proliferation and Pathogenicity in Rabbits

    PubMed Central

    Roetzer, Andreas; Gruener, Corina S.; Haller, Guenter; Beyerly, John; Model, Nina; Eibl, Martha M.

    2016-01-01

    Among the toxin family of bacterial superantigens, the six members of the enterotoxin gene cluster (egc) seem to have unusual characteristics. They are present in the majority of Staphylococcus aureus strains, but their role in disease remains uncertain. We assessed secretion levels, immunogenicity, and toxicity of native and recombinant egc proteins. After having developed enzyme-linked immunosorbent assays, we found different quantities of egc proteins secreted by bacterial isolates. Supernatants induced proliferation of human peripheral blood mononuclear cells. However, purified recombinant egc proteins were shown to have differing superantigenicity potentials. Immunization with identical amounts of all members of egc, and the prominent toxic agent SEB, resulted in neutralizing antisera. Two egc proteins, SEI and SElN, were found to play a predominant role within the cluster. Both displayed the highest potential to activate blood cells, and were essential to be neutralized in supernatants. The application of a supernatant of a strain bearing only egc was sufficient for a lethal outcome in a rabbit model. Again, neutralization of SEI and SElN led to the survival of all tested animals. Finally, nanogram amounts of purified rSEI and rSElN led to lethality in vivo, pointing out the importance of both as virulence determinants among egc superantigens. PMID:27801832

  1. INFECTIOUS PAPILLOMATOSIS OF RABBITS

    PubMed Central

    Shope, Richard E.; Hurst, E. Weston

    1933-01-01

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

  2. PET imaging of apoptosis in tumor-bearing mice and rabbits after paclitaxel treatment with 18F-Labeled recombinant human His10-annexin V

    PubMed Central

    Qin, Haidong; Zhang, Ming-Rong; Xie, Lin; Hou, Yanjie; Hua, Zichun; Hu, Minjin; Wang, Zizheng; Wang, Feng

    2015-01-01

    Monitoring response to chemo- or radiotherapy is of great importance in clinical practice. Apoptosis imaging serves as a very useful tool for the early evaluation of tumor response. The goal of this study was PET imaging of apoptosis with 18F-labeled recombinant human annexin V linked with 10 histidine tag (18F-rh-His10-annexin V) in nude mice bearing an A549 tumor and rabbits bearing a VX2 lung cancer after paclitaxel therapy. 18F-rh-His10-annexin V was prepared by conjugation of rh-His10-annexin V with N-succinimidyl 4-[18F]fluorobenzoate. Biodistribution was determined in mice by the dissection method and small-animal PET. Single-dose paclitaxel (175 mg/m2) was used to induce apoptosis in A549 and VX2 tumor models. 18F-rh-His10-annexin V was injected into A549 mice and VX rabbits to acquire dynamic and static PET images 72 h after paclitaxel treatment. The uptake of 18F-rh-His10-annexin V in apoptotic cells 4 h after induction was 6.45±0.52 fold higher than that in non-induced cells. High focal uptake of 18F-rh-His10-annexin V was visualized in A549 (SUVmax: 0.35±0.13) and VX2 (0.41±0.23) tumor models after paclitaxel treatment, whereas lower uptake was found in the corresponding tumors before treatment (A549 SUVmax: 0.04±0.02; VX2: 0.009±0.002). The apoptotic index was 75.61±11.56% in the treated VX2 cancer, much higher than that in the untreated VX2 (8.03±2.81%). This study demonstrated the feasibility of 18F-rh-His10-annexin V for the detection of apoptosis after chemotherapy in A549 and VX2 tumor models. PMID:25625024

  3. Induction by toxic-shock-syndrome toxin-1 of a circulating tumor necrosis factor-like substance in rabbits and of immunoreactive tumor necrosis factor and interleukin-1 from human mononuclear cells.

    PubMed

    Ikejima, T; Okusawa, S; van der Meer, J W; Dinarello, C A

    1988-11-01

    A shock-like syndrome was induced in rabbits by administering toxic-shock-syndrome toxin-1 (TSST-1); tumor necrosis factor (TNF)-like activity was detected in sera of rabbits 3.5 h after injection, as measured by cytotoxic effects on the tumorigenic L929 murine fibroblast cell line. Appearance of this activity in sera coincided with onset of significant shock-related hemodynamic changes. TSST-1 stimulated release of TNF-like material from rabbit mononuclear cells in culture. Human mononuclear cells also secreted a cytotoxic substance shown to be TNF by radioimmunoassay. Maximal TNF secretion was higher in human mononuclear cells stimulated with TSST-1 than in those stimulated with bacterial lipopolysaccharide. Lipopolysaccharide, however, was a more potent inducer of interleukin-1 alpha and interleukin-1 beta from the same cells than was TSST-1. Because TNF and interleukin-1 act synergistically during induction of a shock-like state, these results suggest that part of the TSST-1-induced shock is due to production of interleukin-1 and TNF.

  4. Genomic Analysis of Companion Rabbit Staphylococcus aureus

    PubMed Central

    Holmes, Mark A.; Harrison, Ewan M.; Fisher, Elizabeth A.; Graham, Elizabeth M.; Parkhill, Julian; Foster, Geoffrey; Paterson, Gavin K.

    2016-01-01

    In addition to being an important human pathogen, Staphylococcus aureus is able to cause a variety of infections in numerous other host species. While the S. aureus strains causing infection in several of these hosts have been well characterised, this is not the case for companion rabbits (Oryctolagus cuniculus), where little data are available on S. aureus strains from this host. To address this deficiency we have performed antimicrobial susceptibility testing and genome sequencing on a collection of S. aureus isolates from companion rabbits. The findings show a diverse S. aureus population is able to cause infection in this host, and while antimicrobial resistance was uncommon, the isolates possess a range of known and putative virulence factors consistent with a diverse clinical presentation in companion rabbits including severe abscesses. We additionally show that companion rabbit isolates carry polymorphisms within dltB as described as underlying host-adaption of S. aureus to farmed rabbits. The availability of S. aureus genome sequences from companion rabbits provides an important aid to understanding the pathogenesis of disease in this host and in the clinical management and surveillance of these infections. PMID:26963381

  5. Autoantibody Production in Rabbits

    PubMed Central

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

    1963-01-01

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

  6. Identification of Antigens of Pathogenic Free-Living Amoebae by Protein Immunoblotting with Rabbit Immune and Human Sera

    DTIC Science & Technology

    1994-09-01

    or more broad bands of less than 1.85 kDa were prominent features in three different Acanthamoeba species. Few cross-reactive antibodies could be...detected between representative species of the three subgroups of Acanthamoeba . Naegleria antigen was likewise serologically distinct, as were...antigens. A prominent band of less than 18.5 kDa was identified in the Acanthamoeba culbertsoni antigen lane in 2 of the 10 human serum specimen pools. When

  7. Genetic analysis of Streptococcus suis isolates from wild rabbits.

    PubMed

    Sánchez del Rey, V; Fernández-Garayzábal, J F; Briones, V; Iriso, A; Domínguez, L; Gottschalk, M; Vela, A I

    2013-08-30

    This work aims to investigate the presence of Streptococcus suis in wild rabbits. A total of 65 S. suis isolates were recovered from 33.3% of the wild rabbits examined. Most isolates (86.2%) belong to genotype cps9. These isolates were further characterized by pulsed field gel electrophoresis (PFGE), multilocus sequence typing (MLST) and virulence genotyping. Overall, S. suis exhibited a low genetic diversity. Only 5 genetic profiles were obtained by PFGE and most isolates (71.4%) were included in two pulsotypes that were also widely distributed among the wild rabbit population. MLST analysis assigned all cps9 isolates into three new singlestones (ST216, ST217 and ST284), which were not genetically related to the European ST87 and Spanish ST61 widespread swine clones, indicating a different genetic background for the S. suis isolates from wild rabbits and pigs. Wild rabbit isolates exhibited the genotype mrp-/epf-/sly-, different from those showed by most of the swine S. suis isolates of the ST87 and ST61 clones. None of the S. suis isolated from wild rabbits exhibited the genotype cps2/mrp+/epf+/sly+ associated with human infections. These results indicate that S. suis isolates from wild rabbits are not genetically related with prevalent clones usually associated with infections in pigs or humans in Europe and do not exhibit either their virulence genotypes. Therefore, although wild rabbits could represent an unknown reservoir of this pathogen, they could not represent a potential risk for pigs or humans.

  8. A method for the production of rheumatoid factor in rabbits

    PubMed Central

    Biro, C. E.

    1968-01-01

    Rabbits rendered immunologically unresponsive to native human IgG and then injected with a single large dose of heat-aggregated human IgG produce an antibody which resembles rheumatoid factor in all its properties that were tested. It is an exclusively IgM antibody which reacts with both human and rabbit (autologous) aggregated IgG, but not with either protein in the native state. PMID:5303049

  9. Lung-targeting drug delivery system of baicalin-loaded nanoliposomes: development, biodistribution in rabbits, and pharmacodynamics in nude mice bearing orthotopic human lung cancer

    PubMed Central

    Wei, Yumeng; Liang, Jing; Zheng, Xiaoli; Pi, Chao; Liu, Hao; Yang, Hongru; Zou, Yonggen; Ye, Yun; Zhao, Ling

    2017-01-01

    The present study aims to develop a kind of novel nanoliposomes for the lung-targeting delivery system of baicalin as a Chinese medicine monomer. Baicalin-loaded nanoliposomes were prepared by the effervescent dispersion and lyophilized techniques. Baicalin-loaded nanoliposomes had an average particle size of 131.7±11.7 nm with 0.19±0.02 polydispersity index, 82.8%±1.24% entrapment efficiency and 90.47%±0.93% of yield and sustaining drug release effect over 24 h and were stable for 12 months at least. In vitro no hemolytic activity was observed for the experimental drug concentration. After intravenous administration of baicalin-loaded nanoliposomes to rabbits, drug concentration in the lungs was the highest among the tested organs at all time points and was significantly higher than that of its solution. For the targeting parameters, the relative intake rate and the ratio of peak concentration of lung were 4.837 and 2.789, respectively. Compared with plasma, liver, spleen, and kidney, the ratios of targeting efficacy (Te)liposomes to (Te)injection of lung were increased by a factor of 14.131, 1.893, 3.357, and 3.470, respectively. Furthermore, the results showed that the baicalin-loaded nanoliposomes did not induce lung injury. Importantly, baicalin-loaded nanoliposomes showed better antitumor therapeutic efficacy in the nude mice bearing orthotopic human lung cancer with the median survival time of blank liposomes (11.40±0.16 days), baicalin solution (17.30±0.47 days), and baicalin-loaded nanoliposomes (25.90±0.53 days). Therefore, the liposome is a promising drug carrier with an excellent lung-targeting property and therapeutic effect for the treatment of lung disease, such as lung cancer. PMID:28096670

  10. Computational Models of Anti-VEGF Therapies in Prostate Cancer

    DTIC Science & Technology

    2014-06-01

    individualized prostate cancer whole-body multicompartment PK/PD models. Each dot represents one individual from the TCGA PrCa dataset. Red = tumor; blue...represents one individual from the TCGA PrCa dataset. Red = tumor; blue = normal. The same data is plotted in each column, sorted using the expression of

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

    PubMed

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

    2012-10-01

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

  12. Epitope specificity of rabbit immunoglobulin G (IgG) elicited by pneumococcal type 23F synthetic oligosaccharide- and native polysaccharide-protein conjugate vaccines: comparison with human anti-polysaccharide 23F IgG.

    PubMed Central

    Alonso de Velasco, E; Verheul, A F; van Steijn, A M; Dekker, H A; Feldman, R G; Fernández, I M; Kamerling, J P; Vliegenthart, J F; Verhoef, J; Snippe, H

    1994-01-01

    Streptococcus pneumoniae type 23F capsular polysaccharide (PS23F) consitss of a repeating glycerol-phosphorylated branched tetrasaccharide. The immunogenicities of the following related antigens were investigated: (i) a synthetic trisaccharide comprising the backbone of one repeating unit, (ii) a synthetic tetrasaccharide comprising the complete repeating unit, and (iii) native PS23F (all three conjugated to keyhole limpet hemocyanin [KLH]) and (iv) formalin-killed S. pneumoniae 23F. All antigens except the trisaccharide-KLH conjugate induced relatively high anti-PS23F antibody levels in rabbits. The epitope specificity of such antibodies was then studied by means of an inhibition immunoassay. The alpha(1-->2)-linked L-rhamnose branch was shown to be immunodominant for immunoglobulin G (IgG) induced by tetrasaccharide-KLH, PS23F-KLH, and killed S. pneumoniae 23F: in most sera L-rhamnose totally inhibited the binding of IgG to PS23F. Thus, there appears to be no major difference in epitope specificity between IgG induced by tetrasaccharide-KLH and that induced by antigens containing the polymeric form of PS23F. Human anti-PS23F IgG (either vaccine induced or naturally acquired) had a different epitope specificity: none of the inhibitors used, including L-rhamnose and tetrasaccharide-KLH, exhibited substantial inhibition. These observations suggest that the epitope recognized by human IgG on PS23F is larger than the epitope recognized by rabbit IgG. Both human and rabbit antisera efficiently opsonized type 23F pneumococci, as measured in a phagocytosis assay using human polymorphonuclear leukocytes. PMID:7509318

  13. SERUM SICKNESS IN RABBITS

    PubMed Central

    Fleisher, Mover S.; Jones, Lloyd

    1931-01-01

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

  14. Rabbit orthopedic surgery.

    PubMed

    Rich, Gregory A

    2002-01-01

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

  15. Experimental rabbit models of Chlamydia pneumoniae infection.

    PubMed Central

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

    1996-01-01

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

  16. Active α-macroglobulin is a reservoir for urokinase after fibrinolytic therapy in rabbits with tetracycline-induced pleural injury and in human pleural fluids

    PubMed Central

    Florova, Galina; Azghani, Ali; Karandashova, Sophia; Kurdowska, Anna K.; Idell, Steven

    2013-01-01

    Intrapleural processing of prourokinase (scuPA) in tetracycline (TCN)-induced pleural injury in rabbits was evaluated to better understand the mechanisms governing successful scuPA-based intrapleural fibrinolytic therapy (IPFT), capable of clearing pleural adhesions in this model. Pleural fluid (PF) was withdrawn 0–80 min and 24 h after IPFT with scuPA (0–0.5 mg/kg), and activities of free urokinase (uPA), plasminogen activator inhibitor-1 (PAI-1), and uPA complexed with α-macroglobulin (αM) were assessed. Similar analyses were performed using PFs from patients with empyema, parapneumonic, and malignant pleural effusions. The peak of uPA activity (5–40 min) reciprocally correlated with the dose of intrapleural scuPA. Endogenous active PAI-1 (10–20 nM) decreased the rate of intrapleural scuPA activation. The slow step of intrapleural inactivation of free uPA (t1/2β = 40 ± 10 min) was dose independent and 6.7-fold slower than in blood. Up to 260 ± 70 nM of αM/uPA formed in vivo [second order association rate (kass) = 580 ± 60 M−1·s−1]. αM/uPA and products of its degradation contributed to durable intrapleural plasminogen activation up to 24 h after IPFT. Active PAI-1, active α2M, and α2M/uPA found in empyema, pneumonia, and malignant PFs demonstrate the capacity to support similar mechanisms in humans. Intrapleural scuPA processing differs from that in the bloodstream and includes 1) dose-dependent control of scuPA activation by endogenous active PAI-1; 2) two-step inactivation of free uPA with simultaneous formation of αM/uPA; and 3) slow intrapleural degradation of αM/uPA releasing active free uPA. This mechanism offers potential clinically relevant advantages that may enhance the bioavailability of intrapleural scuPA and may mitigate the risk of bleeding complications. PMID:23997178

  17. Molecular identification and phylogenesis of dermatophytes isolated from rabbit farms and rabbit farm workers.

    PubMed

    Cafarchia, Claudia; Weigl, Stefania; Figueredo, Luciana A; Otranto, Domenico

    2012-01-27

    Little information is available on the molecular epidemiology of dermatophytoses in rabbit farms and farm workers. A total of 117 isolates belonging to the Trichophyton mentagrophytes complex and 21 isolates of Microsporum canis were collected from rabbits with or without skin lesions, air samples of farms known to harbour these pathogens, and from farm workers with skin lesions, and molecularly characterized. Sequencing of amplicons from the T. mentagrophytes complex and M. canis isolates revealed the presence of one sequence-type for both partial chitin synthase-1 gene (pchs-1) and ribosomal internal transcribed spacer (ITS+), respectively. On the basis of comparative sequence analyses, isolated representing the T. mentagrophytes complex were molecularly identified as Trichophyton interdigitale (zoophilic) Priestley. The M. canis and T. interdigitale pchs-1 sequences herein analysed were 100% homologous to known sequences from different hosts (i.e., cats, dogs, humans and rabbits). Conversely, the ITS+ sequences of T. interdigitale from dogs, pigs and mice were identical, but displayed up to 8.6% difference with those from humans, guinea pigs and rabbits. The results of this study suggest that environmental and clinical isolates of T. interdigitale (zoophilic) and M. canis might share a common origin. Interestingly, the close phylogenetic relationship between T. interdigitale (zoophilic) strains and isolates from dogs, pigs and mice might indicate that these animals represented a reservoir of dermatophyte infection in rabbit farms. These animal species should therefore be considered when setting up control protocols to prevent infections by dermatophytes and their zoonotic transmission.

  18. The Genetic Structure of Domestic Rabbits

    PubMed Central

    Carneiro, Miguel; Afonso, Sandra; Geraldes, Armando; Garreau, Hervé; Bolet, Gerard; Boucher, Samuel; Tircazes, Aurélie; Queney, Guillaume; Nachman, Michael W.; Ferrand, Nuno

    2011-01-01

    Understanding the genetic structure of domestic species provides a window into the process of domestication and motivates the design of studies aimed at making links between genotype and phenotype. Rabbits exhibit exceptional phenotypic diversity, are of great commercial value, and serve as important animal models in biomedical research. Here, we provide the first comprehensive survey of nucleotide polymorphism and linkage disequilibrium (LD) within and among rabbit breeds. We resequenced 16 genomic regions in population samples of both wild and domestic rabbits and additional 35 fragments in 150 rabbits representing six commonly used breeds. Patterns of genetic variation suggest a single origin of domestication in wild populations from France, supporting historical records that place rabbit domestication in French monasteries. Levels of nucleotide diversity both within and among breeds were ∼0.2%, but only 60% of the diversity present in wild populations from France was captured by domestic rabbits. Despite the recent origin of most breeds, levels of population differentiation were high (FST = 17.9%), but the majority of polymorphisms were shared and thus transferable among breeds. Coalescent simulations suggest that domestication began with a small founding population of less than 1,200 individuals. Taking into account the complex demographic history of domestication with two successive bottlenecks, two loci showed deviations that were consistent with artificial selection, including GPC4, which is known to be associated with growth rates in humans. Levels of diversity were not significantly different between autosomal and X-linked loci, providing no evidence for differential contributions of males and females to the domesticated gene pool. The structure of LD differed substantially within and among breeds. Within breeds, LD extends over large genomic distances. Markers separated by 400 kb typically showed r2 higher than 0.2, and some LD extended up to 3,200 kb

  19. Rabbits and hominin survival in Iberia.

    PubMed

    Fa, John E; Stewart, John R; Lloveras, Lluís; Vargas, J Mario

    2013-04-01

    High dependence on the hunting and consumption of large mammals by some hominins may have limited their survival once their preferred quarry became scarce or disappeared. Adaptation to smaller residual prey would have been essential after the many large-bodied species decreased in numbers. We focus on the use of a superabundant species, the rabbit, to demonstrate the importance of this taxon in Iberia as fundamental to predators. We show that the use of the rabbit over time has increased, and that there could have been differential consumption by Neanderthals and Anatomically Modern Humans (AMH). Analysis of bone remains from excavations throughout Iberia show that this lagomorph was a crucial part of the diet of AMH but was relatively unutilised during the Mousterian, when Neanderthals were present. We first present changes in mammalian biomass and mean body mass of mammals over 50,000 years, to illustrate the dramatic loss of large mammalian fauna and to show how the rabbit may have contributed a consistently high proportion of the available game biomass throughout that period. Unlike the Italian Peninsula and other parts of Europe, in Iberia the rabbit has provided a food resource of great importance for predators including hominins. We suggest that hunters that could shift focus to rabbits and other smaller residual fauna, once larger-bodied species decreased in numbers, would have been able to persist. From the evidence presented here, we postulate that Neanderthals may have been less capable of prey-shifting and hence use the high-biomass prey resource provided by the rabbit, to the extent AMH did.

  20. A Herpes Simplex Virus Type 1 Human Asymptomatic CD8+ T-Cell Epitopes-Based Vaccine Protects Against Ocular Herpes in a “Humanized” HLA Transgenic Rabbit Model

    PubMed Central

    Srivastava, Ruchi; Khan, Arif A.; Huang, Jiawei; Nesburn, Anthony B.; Wechsler, Steven L.; BenMohamed, Lbachir

    2015-01-01

    Purpose. A clinical vaccine that protects from ocular herpes simplex virus type 1 (HSV-1) infection and disease still is lacking. In the present study, preclinical vaccine trials of nine asymptomatic (ASYMP) peptides, selected from HSV-1 glycoproteins B (gB), and tegument proteins VP11/12 and VP13/14, were performed in the “humanized” HLA–transgenic rabbit (HLA-Tg rabbit) model of ocular herpes. We recently reported that these peptides are highly recognized by CD8+ T cells from “naturally” protected HSV-1–seropositive healthy ASYMP individuals (who have never had clinical herpes disease). Methods. Mixtures of three ASYMP CD8+ T-cell peptides derived from either HSV-1 gB, VP11/12, or VP13/14 were delivered subcutaneously to different groups of HLA-Tg rabbits (n = 10) in incomplete Freund's adjuvant, twice at 15-day intervals. The frequency and function of HSV-1 epitope-specific CD8+ T cells induced by these peptides and their protective efficacy, in terms of survival, virus replication in the eye, and ocular herpetic disease were assessed after an ocular challenge with HSV-1 (strain McKrae). Results. All mixtures elicited strong and polyfunctional IFN-γ– and TNF-α–producing CD107+CD8+ cytotoxic T cells, associated with a significant reduction in death, ocular herpes infection, and disease (P < 0.015). Conclusions. The results of this preclinical trial support the screening strategy used to select the HSV-1 ASYMP CD8+ T-cell epitopes, emphasize their valuable immunogenic and protective efficacy against ocular herpes, and provide a prototype vaccine formulation that may be highly efficacious for preventing ocular herpes in humans. PMID:26098469

  1. Seroprevalence of Toxoplasma gondii infection in domestic rabbits in Durango State, Mexico.

    PubMed

    Alvarado-Esquivel, Cosme; Alvarado-Esquivel, Domingo; Villena, I; Dubey, J P

    2013-09-01

    There is a lack of information concerning the seroprevalence of Toxoplasma gondii infection in rabbits in northern Mexico. Through a cross sectional study, antibodies to T. gondii were determined in 429 domestic rabbits in Durango State, Mexico using the modified agglutination test. Rabbits were raised in 29 properties in 6 municipalities. Overall, antibodies to T. gondii were found in 70 (16.3%) of 429 rabbits, with titers of 1:25 in 42, 1:50 in 19, 1:100 in 5, 1:200 in 3, and 1:800 in 1. Seropositive rabbits were found in 21 (72.4%) of 29 properties, including 16 of 21 homes, 4 of 5 farms, and 1 of 3 pet shops. This is the first study of T. gondii infection in rabbits in Durango, Mexico. Results indicate that infected rabbits are a potential source of T. gondii infection in humans in Durango State.

  2. Serological survey of hepatitis E virus infection in farmed and pet rabbits in Italy.

    PubMed

    Di Bartolo, Ilaria; De Sabato, L; Marata, A; Martinelli, N; Magistrali, C F; Monini, M; Ponterio, E; Ostanello, F; Ruggeri, F M

    2016-05-01

    The recent identification in rabbits of hepatitis E viruses (HEV) related to viruses infecting humans raises the question of the role of this species as possible HEV reservoir. A serological survey on rabbit HEV infection was conducted in Italy during 2013-2014, including both farmed and pet rabbits. We found an anti-HEV antibody seroprevalence of 3.40 % in 206 farmed rabbits (collected on 7 farms) and 6.56 % in 122 pets. RNA was extracted from IgG-positive sera and analyzed by HEV-specific real-time RT-PCR. None of the samples were positive, confirming that no viremia was present in the presence of IgG. Only one serum sample from a farmed rabbit was positive for IgM, but no HEV RNA was detected in it. Pet rabbit feces were also tested for HEV RNA, with negative results. This finding suggests that HEV is circulating in rabbits in Italy.

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

    PubMed

    Rivers, T M; Berry, G P

    1931-06-30

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

  4. RNA transcripts of full-length cDNA clones of rabbit hepatitis E virus are infectious in rabbits.

    PubMed

    Cossaboom, Caitlin M; Huang, Yao-Wei; Yugo, Danielle M; Kenney, Scott P; Piñeyro, Pablo; Matzinger, Shannon R; Heffron, C Lynn; Pierson, F William; Meng, Xiang-Jin

    2014-11-07

    Hepatitis E virus (HEV), the causative agent of hepatitis E, is a single-stranded positive-sense RNA virus belonging to the family Hepeviridae. At least four genotypes of the family infect humans: genotypes 1 and 2 are transmitted to humans through contaminated water, while genotypes 3 and 4 are zoonotic and have animal reservoirs. A novel strain of HEV recently identified in rabbits is a distant member of genotype 3, and thus poses a potential risk of zoonotic transmission to humans. The objective of this study was to construct and characterize an infectious cDNA clone of the rabbit HEV. Two full-length cDNA clones of rabbit HEV, pT7g-rabHEV and pT7-rabHEV, were constructed and their infectivity was tested by in vitro transfection of Huh7 human liver cells and by direct intrahepatic inoculation of rabbits with capped RNA transcripts. Results showed that positive signal for rabbit HEV protein was detected by an immunofluorescence assay with a HEV-specific antibody in Huh7 human liver cells transfected with capped RNA transcripts from the two full-length cDNA clones. Rabbits intrahepatically inoculated with capped RNA transcripts from each of the two clones developed active HEV infection as evidenced by seroconversion to anti-HEV antibodies, and detection of rabbit HEV RNA in sera and feces of inoculated animals. The availability of a rabbit HEV infectious cDNA clone now affords us the ability to delineate the mechanism of HEV replication and cross-species infection in a small animal model.

  5. The Cutaneous Rabbit Revisited

    ERIC Educational Resources Information Center

    Flach, Rudiger; Haggard, Patrick

    2006-01-01

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

  6. Autoantibody Production in Rabbits

    PubMed Central

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

    1963-01-01

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

  7. Autoantibody production in rabbits

    PubMed Central

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

    1966-01-01

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

  8. 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

  9. Generation of hypoxanthine phosphoribosyltransferase gene knockout rabbits by homologous recombination and gene trapping through somatic cell nuclear transfer.

    PubMed

    Yin, Mingru; Jiang, Weihua; Fang, Zhenfu; Kong, Pengcheng; Xing, Fengying; Li, Yao; Chen, Xuejin; Li, Shangang

    2015-11-02

    The rabbit is a common animal model that has been employed in studies on various human disorders, and the generation of genetically modified rabbit lines is highly desirable. Female rabbits have been successfully cloned from cumulus cells, and the somatic cell nuclear transfer (SCNT) technology is well established. The present study generated hypoxanthine phosphoribosyltransferase (HPRT) gene knockout rabbits using recombinant adeno-associated virus-mediated homologous recombination and SCNT. Gene trap strategies were employed to enhance the gene targeting rates. The male and female gene knockout fibroblast cell lines were derived by different strategies. When male HPRT knockout cells were used for SCNT, no live rabbits were obtained. However, when female HPRT(+/-) cells were used for SCNT, live, healthy rabbits were generated. The cloned HPRT(+/-) rabbits were fertile at maturity. We demonstrate a new technique to produce gene-targeted rabbits. This approach may also be used in the genetic manipulation of different genes or in other species.

  10. Kinematic Analysis of Rabbit Sperm Motion in the Toxicological Assessment of Fertility

    DTIC Science & Technology

    1994-07-01

    into three categories of potency by taking into account the differences in the time course of action against spermatozoa and the dose response for...was carried out using the rabbit as a model of the human for such toxic effects. The exposure of rabbit spermatozoa to a series of compounds was...computer aided sperm analysis. An initial validation study was performed to evaluate the accuracy of CellTrak measurements for rabbit spermatozoa as

  11. Reevaluation of lipolytic activity of growth hormone in rabbit adipocytes.

    PubMed

    Barenton, B; Batifol, V; Combarnous, Y; Dulor, J P; Durand, P; Vezinhet, A

    1984-07-18

    The lipolytic activities of porcine pituitary fractions and purified growth hormone (GH) from human (h), porcine (p), ovine (o) and rabbit (Rb) origin as well as ovine placental lactogen (oPL), were compared to that of ACTH on rabbit adipocytes. All the GH preparations and oPL were equivalent in inhibiting the binding of labelled oGH to liver plasma membranes from pregnant rabbits. ACTH, and to a lesser extent porcine pituitary fractions and hGH, stimulated free fatty acid production by isolated adipocytes. The sensitivity of the adipocytes to these factors was increased when adenosine deaminase was added to the incubation medium. But, RbGH, pGH, oGH and oPL had no effect. We conclude that GH is not directly involved in the control of lipolysis in rabbit adipocytes and that the effect of hGH is rather due to a contamination of this preparation by other pituitary factors.

  12. 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.

  13. Rabbit renotropic system

    SciTech Connect

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

    1988-04-01

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

  14. 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

  15. Naturally occurring antibodies against nerve growth factor in human and rabbit sera: comparison between control and herpes simplex virus-infected patients.

    PubMed

    Dicou, E; Nerrière, V; Labropoulou, V

    1991-11-01

    Antibodies against nerve growth factor (NGF) in sera were detected by enzyme-linked immunosorbent assays (ELISA), by their isolation after passage of sera through NGF immunoadsorbent columns and by their specificity to bind and immunoprecipitate mouse NGF as well as to stain by immunohistochemical methods cellular sites of NGF synthesis. Increased levels of anti-NGF antibodies were found in sera of herpes simplex virus (HSV)-infected patients but not in HSV-inoculated rabbits. As HSV latency is known to be promoted by NGF in vitro, these results may suggest that anti-NGF antibodies modulate the cytokine function of NGF and thus might play a role in HSV infection. The biological function of circulating antibodies against NGF, in general, is now open to future investigation.

  16. Characterization of the rabbit intestinal fructose transporter (GLUT5).

    PubMed Central

    Miyamoto, K; Tatsumi, S; Morimoto, A; Minami, H; Yamamoto, H; Sone, K; Taketani, Y; Nakabou, Y; Oka, T; Takeda, E

    1994-01-01

    Recent studies suggest that the jejunal/kidney-type facilitative glucose transporter (GLUT5) functions as a high-affinity D-fructose transporter. However, its precise role in the small intestine is not clear. In an attempt to identify the fructose transporter in the small intestine, we measured fructose uptake in Xenopus oocytes expressing jejunal mRNA from five species (rat, mouse, rabbit, hamster and guinea-pig). Only jejunal mRNA from the rabbit significantly increased fructose uptake. We also cloned a rabbit GLUT5 cDNA from a jejunal library The predicted amino acid sequence of the 487-residue rabbit GLUT5 showed 72.3 and 67.1% identity with human and rat GLUT5 respectively. Northern-blot analysis revealed GLUT5 transcripts in rabbit duodenum, jejunum and, to a lesser extent, kidney. After separation of rabbit jejunal mRNA on a sucrose density gradient, the fractions that conferred D-fructose transport activity in oocytes also hybridized with rabbit GLUT5 cDNA. Hybrid depletion of jejunal mRNA with a GLUT5 antisense oligonucleotide markedly inhibited the mRNA-induced fructose uptake in oocytes. Immunoblot analysis indicated that GLUT5 (49 kDa) is located in the brush-border membrane of rabbit intestinal epithelial cells. Xenopus oocytes injected with rabbit GLUT5 cRNA exhibited fructose uptake activity with a Km of 11 mM for D-fructose. D-Fructose transport by GLUT5 was significantly inhibited by D-glucose and D-galactose. D-Fructose uptake in brush-border membrane vesicles shows a Km similar to that of GLUT5, but was not inhibited by D-glucose or D-galactose. Finally, cytochalasin B photolabelled a 49 kDa protein in rabbit brush-border-membrane preparations that was immunoprecipitated by antibodies to GLUT5. Our results suggest that GLUT5 functions as a fructose transporter in rabbit small intestine. However, biochemical properties of fructose transport in Xenopus oocytes injected with GLUT5 cRNA differed from those in rabbit jejunal vesicles. Images Figure 2

  17. Effect of Transplanting Various Concentrations of a Composite of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells and Hyaluronic Acid Hydrogel on Articular Cartilage Repair in a Rabbit Model

    PubMed Central

    Ha, Chul-Won; Kim, Jin-A; Rhim, Ji-Heon; Park, Yong-Geun; Chung, Jun Young; Lee, Han-Jun

    2016-01-01

    Background Mesenchymal stem cells (MSCs) are known to have therapeutic potential for cartilage repair. However, the optimal concentration of MSCs for cartilage repair remains unclear. Therefore, we aimed to explore the feasibility of cartilage repair by human umbilical cord blood-derived MSCs (hUCB-MSCs) and to determine the optimal concentrations of the MSCs in a rabbit model. Methods Osteochondral defects were created in the trochlear groove of femur in 55 rabbits. Four experimental groups (11 rabbits/group) were treated by transplanting the composite of hUCB-MSCs and HA with various MSCs concentrations (0.1, 0.5, 1.0, and 1.5 x 107 cells/ml). One control group was left untreated. At 4, 8, and 16 weeks post-transplantation, the degree of cartilage repair was evaluated grossly and histologically. Findings Overall, transplanting hUCB-MSCs and HA hydrogel resulted in cartilage repair tissue with better quality than the control without transplantation (P = 0.015 in 0.1, P = 0.004 in 0.5, P = 0.004 in 1.0, P = 0.132 in 1.5 x 107 cells/ml). Interestingly, high cell concentration of hUCB-MSCs (1.5×107 cells/ml) was inferior to low cell concentrations (0.1, 0.5, and 1.0 x 107 cells/ml) in cartilage repair (P = 0.394,P = 0.041, P = 0.699, respectively). The 0.5 x 107 cells/ml group showed the highest cartilage repair score at 4, 8 and 16 weeks post transplantation, and followed by 0.1x107 cells/ml group or 1.0 x 107 cell/ml group. Conclusions The results of this study suggest that transplantation of the composite of hUCB-MSCs and HA is beneficial for cartilage repair. In addition, this study shows that optimal MSC concentration needs to be determined for better cartilage repair. PMID:27824874

  18. Cross-species infection of pigs with a novel rabbit, but not rat, strain of hepatitis E virus isolated in the United States.

    PubMed

    Cossaboom, Caitlin M; Córdoba, Laura; Sanford, Brenton J; Piñeyro, Pablo; Kenney, Scott P; Dryman, Barbara A; Wang, Youchun; Meng, Xiang-Jin

    2012-08-01

    Hepatitis E virus (HEV) is an important human pathogen. In addition to humans, HEV has also been identified in pig, chicken, mongoose, deer, rat, rabbit and fish. There are four recognized and two putative genotypes of mammalian HEV. Genotypes 1 and 2 are restricted to humans, while genotypes 3 and 4 are zoonotic. The recently identified rabbit HEV is a distant member of genotype 3. Here, we first expressed and purified the recombinant capsid protein of rabbit HEV and showed that the capsid protein of rabbit HEV cross-reacted with antibodies raised against avian, rat, swine and human HEV. Conversely, we showed that antibodies against rabbit HEV cross-reacted with capsid proteins derived from chicken, rat, swine and human HEV. Since pigs are the natural host of genotype 3 HEV, we then determined if rabbit HEV infects pigs. Twenty pigs were divided into five groups of four each and intravenously inoculated with PBS, US rabbit HEV, Chinese rabbit HEV, US rat HEV and swine HEV, respectively. Results showed that only half of the pigs inoculated with rabbit HEV had low levels of viraemia and faecal virus shedding, indicative of active but not robust HEV infection. Infection of pigs by rabbit HEV was further verified by transmission of the virus recovered from pig faeces to naïve rabbits. Pigs inoculated with rat HEV showed no evidence of infection. Preliminary results suggest that rabbit HEV is antigenically related to other HEV strains and infects pigs and that rat HEV failed to infect pigs.

  19. Lens extraction with ultrasound. Experiments in rabbits.

    PubMed Central

    Clarkson, D M; Phillips, C I

    1976-01-01

    The extraction of the rabbit lens is described using a 25 G irrigating needle and a 22 G aspirating needle; at the latter's bevelled tip lens fragmentation occurs due to the longitudinal ultrasonic vibrations generated there--an 'acoustic horn' causes the tip to vibrate with large amplitudes. The use of small needles allows considerable manoeuvrability in the anterior chamber and usually eliminates the need for corneal suturing. Push-pull coupled syringes equate the volume of irrigation with that of aspiration. This procedure makes possible lens extraction through an aperture in the anterior capsule of the rabbit's lens and a similar machine is being constructed for trial on human cataract. Images PMID:1009054

  20. Rabbit IgG directed to a synthetic C-terminal peptide of the major grass pollen allergen Lol p I inhibits human basophil histamine release induced by natural Lol p I.

    PubMed

    van Ree, R; Aalberse, R C

    1995-03-01

    The potential role of allergen-specific IgG antibodies as 'blocking' antibodies in allergen-induced human basophil histamine release was investigated. This was studied in a model with the major grass pollen allergen Lol p I and polyclonal rabbit antisera directed against this allergen and against a synthetic peptide of its C terminus. When allergen and antibodies were allowed to preincubate, Lol p I induced histamine release was inhibited up to 85% by the antiserum against Lol p I. By omitting preincubation, and thereby more closely mimicking an in vivo situation, up to 55% inhibition was realized. This indicates that allergen-specific IgG can act as 'blocking' antibody without preincubation. Immunization of rabbits with a synthetic C-terminal peptide of Lol p I resulted in antibodies reactive with natural Lol p I. Despite their 100-fold lower avidity for Lol p I (as compared with antinatural Lol p I), these antibodies had the capacity to inhibit Lol p I induced histamine release for > 90% (up to 50% without preincubation). This indicates that it is possible to block histamine release induced by a major allergen with low-avidity IgG antibodies directed against a minor proportion of the allergen (25 amino acids). IgE antibodies from the donors studied were unreactive with this synthetic peptide, indicating that for blocking activity identical epitope specificity of IgE and IgG is not essential. This opens interesting perspectives for application of synthetic peptides in immunotherapy, distinct from their effects on T cell reactivity.

  1. Zooprophylaxis: impact of breeding rabbits around houses on reducing the indoor abundance of Phlebotomus papatasi.

    PubMed

    Chelbi, Ifhem; Kaabi, Belhassen; Derbali, Mohamed; Ahmed, Sami Ben Hadj; Dellagi, Koussay; Zhioua, Elyes

    2008-12-01

    Zooprophylaxis is the use of animals to deviate vectors from humans. The indoor abundance of Phlebotomus papatasi in houses with rabbit holes in the peridomestic areas are significantly lower than the indoor abundance in houses without rabbit holes in their peridomestic areas. Introduction of rabbits in artificial underground holes in peridomestic areas reduced significantly the indoor abundance of P. papatasi. Cleaning rabbit holes in peridomestic area by removing all rabbit feces induced a significant increase in the abundance of P. papatasi inside bedrooms. The ecologic niche made around houses in endemic areas by creating active rabbit holes is a major source of attractiveness of P. papatasi, and therefore it may deviate the vector from humans to rabbits. Although rabbit holes are breeding sites for P. papatasi, rabbits are not competent reservoirs for Leishmania major. Our overall findings strongly suggest that zooprophylaxis could be effective in reducing the indoor abundance of P. papatasi and subsequently may be used to control the transmission L. major in rural areas.

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

    PubMed Central

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

    2012-01-01

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

  3. Rumours about wildlife pest introductions: European rabbits in Spain.

    PubMed

    Delibes-Mateos, Miguel

    2017-03-01

    Rumours associated with wildlife are frequent, although they have received little attention in the scientific literature. Studying rumours is important because of their relevance not only in a broad theoretical sense but also in environmental management. The goal of this study is to explore the complexity of the relationships between humans and wildlife through a thematic analysis of rumours associated with allegedly introduced European rabbits (Oryctolagus cuniculus) that cause crop damage in Spain. For this purpose, potential rumours were identified using the Google search engine. Data analysis consisted of reading and re-reading Web-based texts to identify main themes, ideas and topics with the assistance of NVivo 10 software. The analysis identified three main themes: (1) the reviewed websites referred to allegedly introduced rabbits which differed from native rabbits; (2) differences were based on alleged observations of unnatural behaviour, physiology or physical appearance of introduced rabbits; (3) rumours were frequently used in the context of the rabbit management conflict; e.g. farmers accused hunters of releasing harmful rabbits. This study suggests that the analysis of wildlife-release rumours sheds light on the position of parties involved in conflicts associated with the (alleged) introduction of wildlife species. It stresses the importance of rumours in conservation and environmental management, and opens the door to future research.

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

    PubMed

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

    2001-10-01

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

  5. 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).

  6. Immunoreactive Proteins of Bifidobacterium longum ssp. longum CCM 7952 and Bifidobacterium longum ssp. longum CCDM 372 Identified by Gnotobiotic Mono-Colonized Mice Sera, Immune Rabbit Sera and Non-immune Human Sera

    PubMed Central

    Górska, Sabina; Dylus, Ewa; Rudawska, Angelika; Brzozowska, Ewa; Srutkova, Dagmar; Schwarzer, Martin; Razim, Agnieszka; Kozakova, Hana; Gamian, Andrzej

    2016-01-01

    The Bifidobacteria show great diversity in the cell surface architecture which may influence the physicochemical properties of the bacterial cell and strain specific properties. The immunomodulatory role of bifidobacteria has been extensively studied, however studies on the immunoreactivity of their protein molecules are very limited. Here, we compared six different methods of protein isolation and purification and we report identification of immunogenic and immunoreactive protein of two human Bifidobacterium longum ssp. longum strains. We evaluated potential immunoreactive properties of proteins employing polyclonal sera obtained from germ free mouse, rabbit and human. The protein yield was isolation method-dependent and the reactivity of proteins detected by SDS-PAGE and Western blotting was heterogeneous and varied between different serum samples. The proteins with the highest immunoreactivity were isolated, purified and have them sequenced. Among the immunoreactive proteins we identified enolase, aspartokinase, pyruvate kinase, DnaK (B. longum ssp. longum CCM 7952) and sugar ABC transporter ATP-binding protein, phosphoglycerate kinase, peptidoglycan synthethase penicillin-binding protein 3, transaldolase, ribosomal proteins and glyceraldehyde 3-phosphate dehydrogenase (B. longum ssp. longum CCDM 372). PMID:27746766

  7. The antifungal antibiotic, clotrimazole, inhibits chloride secretion by human intestinal T84 cells via blockade of distinct basolateral K+ conductances. Demonstration of efficacy in intact rabbit colon and in an in vivo mouse model of cholera.

    PubMed Central

    Rufo, P A; Merlin, D; Riegler, M; Ferguson-Maltzman, M H; Dickinson, B L; Brugnara, C; Alper, S L; Lencer, W I

    1997-01-01

    The antifungal antibiotic clotrimazole (CLT) blocks directly and with high potency the Ca2+-activated K+ channels of human erythrocytes, erythroleukemia cells, and ferret vascular smooth muscle cells. We recently reported that CLT inhibits Cl- secretion in human intestinal T84 cells, likely by affecting K+ transport (Rufo, P.A., L. Jiang, S.J. Moe, C. Brugnara, S.L. Alper, and W.I. Lencer. 1996. J. Clin. Invest. 98:2066-2075). To determine if CLT had direct effects on K+ conductances in T84 cells, we selectively permeabilized apical membranes of confluent T84 cell monolayers using the ionophore amphotericin B. This technique permits direct measurement of basolateral K+ transport. We found that CLT and a stable des-imidazolyl derivative inhibited directly two pharmacologically distinct basolateral membrane K+conductances, but had no effect on apical membrane Cl- conductances. The effects of CLT on Cl- secretion were also examined in intact tissue. CLT inhibited forskolin-induced Cl- secretion in rabbit colonic mucosal sheets mounted in Ussing chambers by 91%. CLT also inhibited cholera toxin-induced intestinal Cl- secretion in intact mice by 94%. These data provide direct evidence that CLT blocks Cl- secretion in intestinal T84 cells by inhibition of basolateral K+ conductances, and show that CLT inhibits salt and water secretion from intact tissue in vitro and in vivo. The results further support the suggestion that CLT and its metabolites may show clinical efficacy in the treatment of secretory diarrheas of diverse etiologies. PMID:9399958

  8. Nerve growth factor enhances sleep in rabbits.

    PubMed

    Takahashi, S; Krueger, J M

    1999-04-02

    Nerve growth factor (NGF) elicits rapid-eye-movement sleep (REMS) in cats. Removal of NGF receptor-positive cholinergic basal forebrain neurons inhibits REMS in rats. The aim of the present study was to determine the effects of NGF on sleep and brain temperature (Tbr) in rabbits. Male rabbits were implanted with electroencephalograph (EEG) electrodes, a brain thermistor and an intraventricular (i.c.v.) guide cannula. Rabbits received human beta-NGF i.c.v. (0.01, 0.1, 1.0 or 10 microg] and on a separate day, 25 microl pyrogen-free saline i.c.v. as control. EEG and Tbr were recorded for 23 h after injections. The highest two doses of NGF increased both non-REMS and REMS across the 23-h recording period. REMS was enhanced dose-dependently. Tbr was not affected by any dose of NGF. These results suggest that NGF is involved in both REMS and non-REMS regulation.

  9. Species differences in methanol and formic acid pharmacokinetics in mice, rabbits and primates

    SciTech Connect

    Sweeting, J. Nicole; Siu, Michelle; McCallum, Gordon P.; Miller, Lutfiya; Wells, Peter G.

    2010-08-15

    Methanol (MeOH) is metabolized primarily by alcohol dehydrogenase in humans, but by catalase in rodents, with species variations in the pharmacokinetics of its formic acid (FA) metabolite. The teratogenic potential of MeOH in humans is unknown, and its teratogenicity in rodents may not accurately reflect human developmental risk due to differential species metabolism, as for some other teratogens. To determine if human MeOH metabolism might be better reflected in rabbits than rodents, the plasma pharmacokinetics of MeOH and FA were compared in male CD-1 mice, New Zealand white rabbits and cynomolgus monkeys over time (24, 48 and 6 h, respectively) following a single intraperitoneal injection of 0.5 or 2 g/kg MeOH or its saline vehicle. Following the high dose, MeOH exhibited saturated elimination kinetics in all 3 species, with similar peak concentrations and a 2.5-fold higher clearance in mice than rabbits. FA accumulation within 6 h in primates was 5-fold and 43-fold higher than in rabbits and mice respectively, with accumulation being 10-fold higher in rabbits than mice. Over 48 h, FA accumulation was nearly 5-fold higher in rabbits than mice. Low-dose MeOH in mice and rabbits resulted in similarly saturated MeOH elimination in both species, but with approximately 2-fold higher clearance rates in mice. FA accumulation was 3.8-fold higher in rabbits than mice. Rabbits more closely than mice reflected primates for in vivo MeOH metabolism, and particularly FA accumulation, suggesting that developmental studies in rabbits may be useful for assessing potential human teratological risk.

  10. 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

  11. X-Ray structure and biophysical properties of rabbit fibroblast growth factor 1

    SciTech Connect

    Lee, Jihun; Blaber, Sachiko I.; Irsigler, Andre; Aspinwall, Eric; Blaber, Michael

    2010-01-14

    The rabbit is an important and de facto animal model in the study of ischemic disease and angiogenic therapy. Additionally, fibroblast growth factor 1 (FGF-1) is emerging as one of the most important growth factors for novel pro-angiogenic and pro-arteriogenic therapy. However, despite its significance, the fundamental biophysical properties of rabbit FGF-1, including its X-ray structure, have never been reported. Here, the cloning, crystallization, X-ray structure and determination of the biophysical properties of rabbit FGF-1 are described. The X-ray structure shows that the amino-acid differences between human and rabbit FGF-1 are solvent-exposed and therefore potentially immunogenic, while the biophysical studies identify differences in thermostability and receptor-binding affinity that distinguish rabbit FGF-1 from human FGF-1.

  12. Cardiac Tissue Doppler and Tissue Velocity Imaging in Anesthetized New Zealand White Rabbits

    PubMed Central

    Pelosi, Augusta; John, Linda St; Gaymer, Jean; Ferguson, Danielle; Goyal, Sandeep K; Abela, George S; Rubinstein, Jack

    2011-01-01

    New Zealand white rabbits are commonly used in cardiovascular research. Complete echocardiographic examination of the heart includes the evaluation of tissue Doppler (TDI) parameters, yet normal data are unavailable for rabbits. In addition, tissue velocity imaging (TV) is a potentially useful measure of myocardial function that has not yet been applied to rabbits. Anesthetized New Zealand white rabbits (n = 31) underwent echocardiography to establish the feasibility of performing TDI and TV and establishing corresponding reference values. Standard 2D, M-mode, and Doppler measurements were obtained in all rabbits and showed values comparable to previously published data. Interpretable TDI images were obtained in all 31 rabbits and TV in 24 of 31 rabbits. The values obtained were similar to those seen in healthy cats and are comparable to the values found in adult humans. TDI and TV can easily be added to standard echocardiographic evaluation in rabbits. The values from the current study, obtained in normal rabbits, can be used as reference values to improve characterization of cardiac disease in this species. PMID:21640025

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

    PubMed

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

    2015-08-01

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

  14. Cell-mediated transgenesis in rabbits: chimeric and nuclear transfer animals.

    PubMed

    Zakhartchenko, V; Flisikowska, T; Li, S; Richter, T; Wieland, H; Durkovic, M; Rottmann, O; Kessler, B; Gungor, T; Brem, G; Kind, A; Wolf, E; Schnieke, A

    2011-02-01

    The ability to perform precise genetic engineering such as gene targeting in rabbits would benefit biomedical research by enabling, for example, the generation of genetically defined rabbit models of human diseases. This has so far not been possible because of the lack of functional rabbit embryonic stem cells and the high fetal and perinatal mortality associated with rabbit somatic cell nuclear transfer. We examined cultured pluripotent and multipotent cells for their ability to support the production of viable animals. Rabbit putative embryonic stem (ES) cells were derived and shown capable of in vitro and in vivo pluripotent differentiation. We report the first live born ES-derived rabbit chimera. Rabbit mesenchymal stem cells (MSCs) were derived from bone marrow, and multipotent differentiation was demonstrated in vitro. Nuclear transfer was carried out with both cell types, and embryo development was assessed in vitro and in vivo. Rabbit MSCs were markedly more successful than ES cells as nuclear donors. MSCs were transfected with fluorescent reporter gene constructs and assessed for nuclear transfer competence. Transfected MSCs supported development with similar efficiency as normal MSCs and resulted in the first live cloned rabbits from genetically manipulated MSCs. Reactivation of fluorescence reporter gene expression in reconstructed embryos was investigated as a means of identifying viable embryos in vitro but was not a reliable predictor. We also examined serial nuclear transfer as a means of rescuing dead animals.

  15. Cotransplantation of human umbilical cord-derived mesenchymal stem cells and umbilical cord blood-derived CD34⁺ cells in a rabbit model of myocardial infarction.

    PubMed

    Li, Tong; Ma, Qunxing; Ning, Meng; Zhao, Yue; Hou, Yuelong

    2014-02-01

    The objective of the study is to investigate the effect of hypoxic preconditioning on the immunomodulatory properties of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and the effect of cotransplantation of hUC-MSCs and human umbilical cord blood (hUCB)-derived CD34(+) cells in a rabbit model of myocardial infarction. hUC-MSCs with or without hypoxic preconditioning by cobalt chloride were plated in a 24-well plate, and then cocultured with hUCB-CD34(+) cells and PBMCs for 96 h at 37 °C in a 5% CO₂ incubator. For the negative control, hUC-MSCs were omitted. The groups were divided as follows: A1 = HP-MSCs + hUCB-CD34(+) cells + PBMC, A2 = hUC-MSCs + hUCB-CD34(+) cells + PBMC, Negative Control = hUCB-CD34(+) cells + PBMC. Culture supernatants of each group were collected, and the IL-10 and IFN-γ levels were measured by ELISA. A rabbit model of MI was established using a modified Fujita method. The animals were then randomized into three groups and received intramyocardial injections of 0.4 ml of PBS alone (n = 8, PBS group), hUC-MSCs in PBS (n = 8, hUC-MSCs group), or hUC-MSCs + CD34(+) cells in PBS (n = 8, Cotrans group), at four points in the infarct border zone. Echocardiography was performed at baseline, 4 weeks after MI induction, and 4 weeks after cell transplantation, respectively. Stem cell differentiation and neovascularization in the infracted area were characterized for the presence of cardiac Troponin I (cTnI) and CD31 by immunohistochemical staining, and the extent of myocardial fibrosis was evaluated by hematoxylin and eosin (H&E) and Masson's trichrome. IFN-γ was 27.00 ± 1.11, 14.20 ± 0.81, and 7.22 ± 0.14 pg/ml, and IL-10 was 31.68 ± 3.08, 61.42 ± 1.08, and 85.85 ± 1.80 pg/ml for the Control, A1 and A2 groups, respectively, which indicated that hUCB-CD34(+) cells induced immune reaction of peripheral blood mononuclear cells, whereas both hUC-MSCs and HP-MSCs showed an immunosuppressive effect, which, however, was attenuated

  16. Oculoscopy in Rabbits and Rodents.

    PubMed

    Jekl, Vladimir; Hauptman, Karel; Knotek, Zdenek

    2015-09-01

    Ophthalmic diseases are common in rabbits and rodents. Fast and definitive diagnosis is imperative for successful treatment of ocular diseases. Ophthalmic examination in rabbits and rodents can be challenging. Oculoscopy offers great magnification for the examination of the ocular structures in such animals, including the evaluation of cornea, anterior eye chamber, limbus, iris, lens, and retina. To date, oculoscopy has been described only sporadically and/or under experimental conditions. This article describes the oculoscopy technique, normal and abnormal ocular findings, and the most common eye disorders diagnosed with the aid of endoscopy in rabbits and rodents.

  17. Cloning and functional characterization of the rabbit C-C chemokine receptor 2

    PubMed Central

    Lu, Deshun; Yuan, Xiu-juan; Evans, Robert J; Pappas, Amy T; Wang, He; Su, Eric W; Hamdouchi, Chafiq; Venkataraman, Chandrasekar

    2005-01-01

    Background CC-family chemokine receptor 2 (CCR2) is implicated in the trafficking of blood-borne monocytes to sites of inflammation and is implicated in the pathogenesis of several inflammatory diseases such as rheumatoid arthritis, multiple sclerosis and atherosclerosis. The major challenge in the development of small molecule chemokine receptor antagonists is the lack of cross-species activity to the receptor in the preclinical species. Rabbit models have been widely used to study the role of various inflammatory molecules in the development of inflammatory processes. Therefore, in this study, we report the cloning and characterization of rabbit CCR2. Data regarding the activity of the CCR2 antagonist will provide valuable tools to perform toxicology and efficacy studies in the rabbit model. Results Sequence alignment indicated that rabbit CCR2 shares 80 % identity to human CCR2b. Tissue distribution indicated that rabbit CCR2 is abundantly expressed in spleen and lung. Recombinant rabbit CCR2 expressed as stable transfectants in U-937 cells binds radiolabeled 125I-mouse JE (murine MCP-1) with a calculated Kd of 0.1 nM. In competition binding assays, binding of radiolabeled mouse JE to rabbit CCR2 is differentially competed by human MCP-1, -2, -3 and -4, but not by RANTES, MIP-1α or MIP-1β. U-937/rabbit CCR2 stable transfectants undergo chemotaxis in response to both human MCP-1 and mouse JE with potencies comparable to those reported for human CCR2b. Finally, TAK-779, a dual CCR2/CCR5 antagonist effectively inhibits the binding of 125I-mouse JE (IC50 = 2.3 nM) to rabbit CCR2 and effectively blocks CCR2-mediated chemotaxis. Conclusion In this study, we report the cloning of rabbit CCR2 and demonstrate that this receptor is a functional chemotactic receptor for MCP-1. PMID:16001983

  18. Molecular characterization and expression analysis of fat mass and obesity-associated gene in rabbit.

    PubMed

    Xing, Jinyi; Jing, Wenqian; Jiang, Yunliang

    2013-12-01

    Fat mass and obesity-associated (FTO) gene codes for a nuclear protein of the AlkB related nonhaem iron and 2-oxoglutaratedependent oxygenase superfamily, and is involved in animal fat deposition and human obesity. In this work, the molecular characterization and expression features of rabbit (Oryctolagus cuniculus) FTO cDNA were analysed. The rabbit FTO cDNA with a size of 2158 bp was cloned, including 1515 bp of the open reading frame that encoded a basic protein of 504 amino acids. Homologous comparison indicated that the rabbit FTO shared 36.36-91.88% identity with those from other species and phylogenetic analysis showed that the rabbit FTO is closely related to human, but more distantly related to zebrafish. The New Zealand rabbit FTO mRNA was detected in all tissues examined, with the highest levels found in the spleen and the lowest found in the kidney. However, no significant differences were seen in cerebellum, corpora quadrigemina, medulla oblongata and cerebral cortex of commercial adult rabbits. Moreover, mRNA levels of FTO in liver tissues were significantly increased in lactating New Zealand rabbits compared with 70-day-old, 90-day-old and gestating rabbits (P < 0.05). In contrast, FTO mRNA levels were significantly lower in longissimus dorsi muscle of 90-day-old New Zealand rabbits than in 70-day-old rabbits (P <0.05). However, the expression levels of FTO in mammary gland and ovary of gestating and lactating rabbits were not significantly different (P > 0.05).

  19. Urethral healing in rabbits.

    PubMed

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

    1992-08-01

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

  20. Evaluation of haematological, biochemical and histopathological parameters of transgenic rabbits.

    PubMed

    Jurcik, R; Suvegova, K; Hanusova, E; Massanyi, P; Ryban, L; Chrenek, P

    2007-11-01

    The aim of our study was to compare the hFVIII mRNA expression in different organs, pathological changes and selected haematological and biochemical blood parameters between transgenic and non-transgenic rabbits from F3 generation. Selected physiological parameters of 3- to 4-month-old transgenic rabbits from F3 generation carrying human factor VIII gene (hFVIII) were analysed and compared with those of non-transgenic ones. Before slaughtering, the blood for haematological and biochemical analysis was taken from the central ear artery. Pathological and histological examination of vital organs and RT-PCR analysis of several tissue organs of transgenic and non-transgenic animals were performed after slaughtering. Except for the mammary gland tissue, slight hfVIII mRNA expression in the spleen, lung and brain and none expression in the liver, kidney, skeletal muscle and heart of rabbits were recorded. pathological examination of vital organs showed some pathological changes in both transgenic and non-transgenic rabbits which were confirmed by histological qualitative evaluations. Statistically significant lower values of blood haemoglobin in blood of transgenic (11.86+/-0.86) animals compared with non-transgenic (12.41+/-1.02, P<0.05) ones and lower parameters of HCT (39.22+/-2.44 versus 40.89+/-2.26, P<0.01) in blood of transgenic rabbits were observed. Parameters of WBC, RBC and PLT showed no significant differences between the analysed groups. All biochemical serum parameters of transgenic rabbits were higher in comparison with non-transgenic ones. Significant differences were found in the concentration of the urea, AST and GMT between transgenic and non-transgenic animals (P<0.001) and in the total protein content, the difference was significant at P<0.05. In conclusion, our results showed that no considerable impact on the general health was found in transgenic rabbits.

  1. Vaccinia virus K1L protein supports viral replication in human and rabbit cells through a cell-type-specific set of its ankyrin repeat residues that are distinct from its binding site for ACAP2.

    PubMed

    Meng, Xiangzhi; Xiang, Yan

    2006-09-15

    Vaccinia virus (VV) K1L is a host-range gene and encodes a protein comprised of six ankyrin repeats (ANKs). We showed here that a large portion of the K1L protein, except ankyrin repeat 1 (ANK1) and C-terminal halves of ANK2 and ANK3, can be deleted or substituted with an unrelated ANK with no adverse effect on VV replication in human HeLa cells. In contrast, only ANK4 and ANK6 can be mutated without impairing VV replication in rabbit RK13 cells. The growth rate of VV in HeLa cells was reduced differentially by substituting phenylalanine 82 or serine 83 of ANK2 and abolished completely by substituting both residues. These substitutions, however, did not affect K1L's ability to bind ACAP2, a GTPase-activating protein for ARF6. Our data support the hypothesis that surface residues of a few consecutive K1L ANKs mediate the host-range function by interacting with protein factors that are distinct from ACAP2.

  2. Glomerular lesions induced in the rabbit by physicochemically altered homologous IgG.

    PubMed Central

    Cavalot, F.; Miyata, M.; Vladutiu, A.; Terranova, V.; Dubiski, S.; Burlingame, R.; Tan, E.; Brentjens, J.; Milgrom, F.; Andres, G.

    1992-01-01

    Immunization of rabbits with physicochemically altered homologous or even autologous IgG induces formation of antibodies combining with IgG of rabbit and of foreign species. Cardiac but not renal lesions were reported in such animals. This study examined the nephritogenic potential of the immune response to cationized or heat-aggregated homologous IgG of b9 or b4 allotype in rabbits of the b4 allotype. Rabbits injected with either b9 or b4 cationized IgG produced antibodies reactive with rabbit and human IgG and with histones; they also developed abnormal glomerular deposits of IgG b4 and C3 corresponding to alterations of the glomerular basement membranes (GBM). Rabbits injected with either b9 or b4 aggregated IgG developed antibodies reactive with rabbit and human IgG and abnormal glomerular deposits of IgG b4 and C3 in the GBM and in the mesangium with subendothelial and mesangial electron-dense deposits. Some rabbits in both groups had proliferative and exudative glomerulonephritis and proteinuria. The results showed that immunization of rabbits with physicochemically altered homologous IgG induces an immune response to rabbit and human IgG and to histones as well as glomerular deposits of autologous IgG and C3 and other glomerular lesions. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 Figure 16 Figure 17 Figure 18 Figure 19 Figure 20 Figure 21 Figure 22 Figure 23 Figure 24 Figure 25 Figure 26 Figure 27 Figure 28 Figure 29 Figure 30 PMID:1546743

  3. Molecular detection of Cryptosporidium cuniculus in rabbits in Australia.

    PubMed

    Nolan, Matthew J; Jex, Aaron R; Haydon, Shane R; Stevens, Melita A; Gasser, Robin B

    2010-12-01

    In the United Kingdom, rabbits have been reported to harbour genotypes of Cryptosporidium (now recognized as C. cuniculus) identical to those from human patients exhibiting symptoms of cryptosporidiosis. The high density of rabbits in many regions of Australia, including both rural and urban as well as natural water catchments areas, and the absence of any information on Cryptosporidium from lagomorphs in this country stimulated the present study. We undertook an epidemiological study that genetically characterized Cryptosporidium from rabbits from four locations in Victoria by PCR-coupled sequencing and phylogenetic analysis of sequence data for loci within the small subunit of nuclear ribosomal RNA (SSU; for specific identification) and the 60kDa glycoprotein gene (gp60; for genotypic/subgenotypic identification). Cryptosporidium was detected in 12 (6.8%) of 176 individual faecal samples. For SSU, all 12 sequences were identical to each other and to that of C. cuniculus. For pgp60, all corresponding sequences matched the known genotype Vb, and were classified as subgenotype VbA23R3 (n=11) and VbA26R4 (n=1), which are both new records. Present evidence indicates that genotype Vb is limited to rabbits; however, it would be premature to conclude that this genotype is not zoonotic. Future studies should focus on the zoonotic potential of C. cuniculus from rabbits and a wide range of yet unstudied animals. (Nucleotide sequences reported in this paper are available in the GenBank database under accession nos. HM852431-HM852433).

  4. 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.

  5. Rabbit anti-rabies immunoglobulins production and evaluation.

    PubMed

    Liu, Xinjian; Liu, Qiongqiong; Feng, Xiaomin; Tang, Qi; Wang, Zhongcan; Li, Suqing; Feng, Zhenqing; Zhu, Jin; Guan, Xiaohong

    2011-04-01

    Due to the disadvantages of human and equine rabies immunoglobulin, it is necessary to develop a substitute for HRIG and ERIG, especially for those people living in the developing countries. Because of higher affinity and lower immunogenicity of rabbit's immunoglobulins, anti-rabies immunoglobulins specific to rabies virus were produced in rabbits as a bioreactor, and had been characterized by ELISA, affinity assay, immunofluorescence assay (IFA), immunocytochemistry, rapid fluorescent focus inhibition test (RFFIT). ELISA, affinity assay and IFA showed that rabbit RIG (RRIG) bound specifically to rabies virions. RFFIT result showed that RRIG has neutralization activity. This result was confirmed in vivo in a Kunming mouse challenge model and the protection rate of the treatment with RRIG was higher (25%) than that offered by HRIG when mice were challenged with a lethal RV dose. Our results demonstrate that RRIG is safe and efficacious as a candidate drug to replace rabies immunoglobulin in post-exposure prophylaxis.

  6. Use of host population reduction to control wildlife infection: rabbits and paratuberculosis.

    PubMed

    Davidson, R S; Marion, G; White, P C L; Hutchings, M R

    2009-01-01

    Reduction in wildlife populations is a common method for the control of livestock infections which have wildlife hosts, but its success is dependent on the characteristics of the infection itself, as well as on the spatial and social structure of the wildlife host. Paratuberculosis (Mycobacterium avium subsp. paratuberculosis; Map) is a widespread and difficult infection to control in livestock populations and also has possible links to Crohn's disease in humans. Rabbits have recently been identified as a key wildlife species in terms of paratuberculosis persistence in the environment and risk to the wider host community, including cattle. Here we use a spatially explicit stochastic simulation model of Map dynamics in rabbit populations to quantify the effects of rabbit population control on infection persistence. The model parameters were estimated from empirical studies of rabbit population dynamics and rabbit-to-rabbit routes of Map transmission. Three rabbit control strategies were compared: single unrepeated population reductions based on removing individual animals; single unrepeated population reductions based on removal of entire social groups; and repeated annual population reductions based on removing individual animals. Unrealistically high rabbit culls (>95% population reduction) are needed if infection is to be eradicated from local rabbit populations with a single one-off population reduction event, either of individuals or social groups. Repeated annual culls are more effective at reducing the prevalence of infection in rabbit populations and eradicating infection. However, annual population reductions of >40% are required over extended periods of time (many years). Thus, using an approach which is both highly conservative and parsimonious with respect to estimating lower bounds on the time to eradicate the infection, we find that Map is extremely persistent in rabbit populations and requires significant and prolonged effort to achieve control.

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

    PubMed Central

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

    2015-01-01

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

  8. [Foamy alveolar macrophages in various lung diseases, and their origin in rabbit lungs].

    PubMed

    Yuasa, K; Kanazawa, T

    1995-07-01

    The present studies were done to clarify the significance of foamy alveolar macrophages (FAM) in lung diseases, and the mechanism of the production of macrophages in rabbit lungs. Human subjects consisted of 18 normal volunteers (NV) and 47 patients with lung disorders: chronic bronchitis (CB), 7 cases; pulmonary fibrosis (PF), 8 cases; old pulmonary tuberculosis (OPT), 7 cases; lung cancer (LC), 20 cases; and bronchiectasis (BE), 5 cases. In each case, over 30 macrophages in the BALF were observed by transmission electron microscopy. There were no significant differences in the percentage of FAm in the BALF among NV, CB, and PF. Furthermore, OPT and LC were not significantly different. Many more FAM were seen in OPT and LC than in NV, CB, and PF (p < 0.005). The percentage of FAM obtained from BE was much higher than that from OPT and LC (p < 0.005). These results suggest that the grade of foamy change in macrophages differs among lung diseases. Three groups of rabbits were studied. Group I rabbits (n = 6) were control, Group II rabbits (n = 6) underwent bronchial clamping, and Group III rabbits (n = 6) underwent complete replacement of blood with saline. The number of macrophages and type II cells was much greater in Group II rabbits than in Group I rabbits. In Group III rabbits, the number of macrophages was lower than in Group I rabbits. In Group III rabbits, vacuole-like structures were seen in the cytoplasma of type II cells, but not from in macrophages. These findings suggest that anoxia and blood flow are important for the appearance of macrophages in alveolar space. Group III rabbits had few alveolar macrophages. Therefore, alveolar macrophages may be derived from monocytes in blood.

  9. Unique Properties of the Rabbit Prion Protein Oligomer

    PubMed Central

    Yu, Ziyao; Huang, Pei; Yu, Yuanhui; Zheng, Zhen; Huang, Zicheng; Guo, Chenyun; Lin, Donghai

    2016-01-01

    Prion diseases, also known as transmissible spongiform encephalopathies (TSEs), are a group of fatal neurodegenerative disorders infecting both humans and animals. Recent works have demonstrated that the soluble prion protein oligomer (PrPO), the intermediate of the conformational transformation from the host-derived cellular form (PrPC) to the disease-associated Scrapie form (PrPSc), exerts the major neurotoxicity in vitro and in vivo. Rabbits show strong resistance to TSEs, the underlying mechanism is unclear to date. It is expected that the relative TSEs-resistance of rabbits is closely associated with the unique properties of rabbit prion protein oligomer which remain to be addressed in detail. In the present work, we prepared rabbit prion protein oligomer (recRaPrPO) and human prion protein oligomer (recHuPrPO) under varied conditions, analyzed the effects of pH, NaCl concentration and incubation temperature on the oligomerization, and compared the properties of recRaPrPO and recHuPrPO. We found that several factors facilitated the formation of prion protein oligomers, including low pH, high NaCl concentration, high incubation temperature and low conformational stability of monomeric prion protein. RecRaPrPO was formed more slowly than recHuPrPO at physiological-like conditions (< 57°C, < 150 mM NaCl). Furthermore, recRaPrPO possessed higher susceptibility to proteinase K and lower cytotoxicity in vitro than recHuPrPO. These unique properties of recRaPrPO might substantially contribute to the TSEs-resistance of rabbits. Our work sheds light on the oligomerization of prion proteins and is of benefit to mechanistic understanding of TSEs-resistance of rabbits. PMID:27529173

  10. The Alpha-1A Adrenergic Receptor in the Rabbit Heart

    PubMed Central

    Myagmar, Bat-Erdene; Swigart, Philip M.; Baker, Anthony J.; Simpson, Paul C.

    2016-01-01

    The alpha-1A-adrenergic receptor (AR) subtype is associated with cardioprotective signaling in the mouse and human heart. The rabbit is useful for cardiac disease modeling, but data on the alpha-1A in the rabbit heart are limited. Our objective was to test for expression and function of the alpha-1A in rabbit heart. By quantitative real-time reverse transcription PCR (qPCR) on mRNA from ventricular myocardium of adult male New Zealand White rabbits, the alpha-1B was 99% of total alpha-1-AR mRNA, with <1% alpha-1A and alpha-1D, whereas alpha-1A mRNA was over 50% of total in brain and liver. Saturation radioligand binding identified ~4 fmol total alpha-1-ARs per mg myocardial protein, with 17% alpha-1A by competition with the selective antagonist 5-methylurapidil. The alpha-1D was not detected by competition with BMY-7378, indicating that 83% of alpha-1-ARs were alpha-1B. In isolated left ventricle and right ventricle, the selective alpha-1A agonist A61603 stimulated a negative inotropic effect, versus a positive inotropic effect with the nonselective alpha-1-agonist phenylephrine and the beta-agonist isoproterenol. Blood pressure assay in conscious rabbits using an indwelling aortic telemeter showed that A61603 by bolus intravenous dosing increased mean arterial pressure by 20 mm Hg at 0.14 μg/kg, 10-fold lower than norepinephrine, and chronic A61603 infusion by iPRECIO programmable micro Infusion pump did not increase BP at 22 μg/kg/d. A myocardial slice model useful in human myocardium and an anthracycline cardiotoxicity model useful in mouse were both problematic in rabbit. We conclude that alpha-1A mRNA is very low in rabbit heart, but the receptor is present by binding and mediates a negative inotropic response. Expression and function of the alpha-1A in rabbit heart differ from mouse and human, but the vasopressor response is similar to mouse. PMID:27258143

  11. Metallothionein in rabbit kidneys preserved for transplantation.

    PubMed

    Elinder, C G; Lundgren, G; Nordberg, M; Palm, B; Piscator, M

    1984-03-01

    Thirteen rabbits were given repeated cadmium injections to achieve cadmium concentrations in kidney cortex ranging from 0.05 to 1 mmole Cd/kg wet weight. Another four animals served as controls. One kidney from each animal was frozen directly to -70 degrees C whereas the other kidney was kept for 24 hr at +4 degrees C in a preservative (Sachs' solution) to simulate conditions for preservation of human donor kidneys before transplantation. Protein binding of cadmium, zinc and copper in kidney homogenates and the concentration of metallothionein (MT) were measured in the kidney that was frozen directly and in the kidney that had been preserved. No gross differences in either the protein binding of cadmium, zinc and copper or in the MT content were seen between the directly frozen and preserved kidneys from the same animal. This indicates that MT is not rapidly broken down in rabbit kidneys which have been preserved similarly to human donor kidneys for 24 hr in a standard preservative solution prior to a transplantation.

  12. Seroprevalence and Risk Factors of Chlamydia Infection in Domestic Rabbits (Oryctolagus cuniculus) in China.

    PubMed

    Ni, Xiaoting; Qin, Siyuan; Lou, Zhilong; Ning, Hongrui; Sun, Xiaolin

    2015-01-01

    Chlamydia spp. are obligate intracellular bacteria distributed all over the world, known to cause various forms of diseases in animals and humans. In the present study, a serological survey was conducted to detect the seroprevalence and risk factors associated with rabbit chlamydiosis in northeast China, including Liaoning province, Jilin province, Heilongjiang province, and Inner Mongolia Autonomous Region. Antibodies to Chlamydia were determined by indirect hemagglutination assay (IHA). The overall seroprevalence was estimated at 17.88% in total of 800 blood samples. The Chlamydia seroprevalence varied in domestic rabbits from different factors, and genders of domestic rabbits were considered as major risk factors associated with Chlamydia infection. Our study revealed a widespread and high prevalence of Chlamydia infection in domestic rabbits in northeast China, with higher exposure risk in female domestic rabbits. These findings suggested the potential importance of domestic rabbits in the transmission of zoonotic Chlamydia infection, and thus Chlamydia should be taken into consideration in diagnosing rabbit diseases. To our knowledge, there is no report of Chlamydia infection in domestic rabbits in China and the results extend the host range for Chlamydia, which has important implications for public health and the local economy.

  13. Studies on the structural stability of rabbit prion probed by molecular dynamics simulations of its wild-type and mutants.

    PubMed

    Zhang, Jiapu

    2010-05-07

    Prion diseases are invariably fatal and highly infectious neurodegenerative diseases that affect humans and animals. Rabbits are the only mammalian species reported to be resistant to infection from prion diseases isolated from other species (Vorberg et al., 2003). Fortunately, the NMR structure of rabbit prion (124-228) (PDB entry 2FJ3), the NMR structure of rabbit prion protein mutation S173N (PDB entry 2JOH) and the NMR structure of rabbit prion protein mutation I214V (PDB entry 2JOM) were released recently. This paper studies these NMR structures by molecular dynamics simulations. Simulation results confirm the structural stability of wild-type rabbit prion, and show that the salt bridge between D177 and R163 greatly contributes to the structural stability of rabbit prion protein.

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

    PubMed

    Zimmermann, R

    1990-01-01

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

  15. HEREDITARY OSTEOPETROSIS OF THE RABBIT

    PubMed Central

    Pearce, Louise; Brown, Wade H.

    1948-01-01

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

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

    PubMed

    Matsui, S; Fu, M L

    2001-01-01

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

  17. European Rabbits as Reservoir for Coxiella burnetii

    PubMed Central

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

    2015-01-01

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

  18. INSULIN-INDUCED GLOMERULOSCLEROSIS IN THE RABBIT

    PubMed Central

    Mohos, Steven C.; Hennigar, Gordon R.; Fogelman, John A.

    1963-01-01

    An attempt has been made to induce intercapillary glomerulosclerosis in rabbits by immunization with insulin incorporated in Freund's adjuvant and followed by repeated challenges with subcutaneously given insulin. It was observed that lesions resembling human diabetic glomerulosclerosis with occasional nodule-like formation could be produced and that the challenge insulin injections produced proteinuria. The presence of a delayed type of hypersensitivity seemed necessary for the lesions to occur as did the dissemination of the immunizing material to the kidneys. The experiment also disclosed that intravenously given DIS-tagged insulin localizes in a subtly different kind of glomerular lesion with different staining properties. The significance of these findings and the possible role of insulin treatment in the pathogenesis of human diabetic glomerulosclerosis is discussed. PMID:14087614

  19. Effect of feeding growing-fattening rabbits a diet supplemented with whole white lupin (Lupinus albus cv. Amiga) seeds on fatty acid composition and indexes related to human health in hind leg meat and perirenal fat.

    PubMed

    Volek, Zdeněk; Marounek, Milan

    2011-01-01

    A total of 20 weaned rabbits (33 days old) (10 per treatment) were fed one of two diets that included 150 g of sunflower meal (SF)/kg of diet or 120 g of whole white lupin (WL)/kg of diet for 42 days. The WL diet contained less saturated fatty acids (SFA) and polyunsaturated fatty acids (PUFA) but more monounsaturated fatty acids (MUFA) than the SF diet. The WL diet significantly decreased SFA and PUFA content, as well as the PUFA n-6/PUFA n-3 ratio and saturation, atherogenic and thrombogenic indexes in hind leg meat. The fatty acid composition in perirenal fat was similar to that of hind leg meat; however, significantly higher MUFA levels were observed in rabbits fed the WL diet. Thus, feeding rabbits the WL diet affected the fatty acid profile of hind leg meat and perirenal fat in a favourable manner.

  20. Transgenic rabbits for the production of biologically-active recombinant proteins in the milk.

    PubMed

    Castro, F O; Limonta, J; Rodriguez, A; Aguirre, A; de la Fuente, J; Aguilar, A; Ramos, B; Hayes, O

    1999-11-01

    The use of live bioreactors for the expression of human genes in the mammary gland of transgenic animals is one of the most cost-effective ways for the production of valuable recombinant therapeutic proteins. Among the transgenic species used so far, rabbits are good candidates for the expression of tens to hundreds of grams of complex proteins in the milk during lactation. The lactating mammary gland of rabbits has proven to be effective in the processing of complex proteins. In this work. the potential use of rabbits as bioreactors is discussed based on our results and the published data.

  1. Pharmacokinetic profile of cocaine following intravenous administration in the female rabbit

    PubMed Central

    Parlaman, Joshua P.; Thompson, Barbara L.; Levitt, Pat; Stanwood, Gregg D.

    2007-01-01

    Prenatal cocaine exposure in a rabbit intravenous model has revealed selective disruption of brain development and pharmacological responsiveness. We therefore examined the pharmacokinetic properties of cocaine in this model. Dutch-belted rabbits were surgically implanted with a catheter in the carotid artery, allowed to recover, and then injected intravenously with a cocaine bolus. Cocaine and benzoylecgonine concentrations were measured in arterial blood plasma and analyzed by nonlinear regression and noncompartmental analyses. Peak cocaine concentration occurred by 30s, was transient, and distribution was rapid. The profile of cocaine in the rabbit is similar to that observed in humans using cocaine at recreational doses. PMID:17383635

  2. Blocking of tumor necrosis factor activity promotes natural repair of osteochondral defects in rabbit knee

    PubMed Central

    2009-01-01

    Background and purpose Osteochondral defects have a limited capacity for repair. We therefore investigated the effects of tumor necrosis factor (TNF) signal blockade by etanercept (human recombinant soluble TNF receptor) on the repair of osteochondral defects in rabbit knees. Material and methods Osteochondral defects (5 mm in diameter) were created in the femoral patellar groove in rabbits. Soon after the procedure, a first subcutaneous injection of etanercept was performed. This single injection or, alternatively, 4 injections in total (twice a week for 2 weeks) were given. Each of these 2 groups was divided further into 3 subgroups: a low-dose group (0.05 μg/kg), an intermediate-dose group (0.4 μ g/kg), and a high-dose group (1.6 μ g /kg) with 19 rabbits in each. As a control, 19 rabbits were injected with water alone. The rabbits in each subgroup were killed 4 weeks (6 rabbits), 8 weeks (6 rabbits), or 24 weeks (7 rabbits) after surgery and repair was assessed histologically. Results Histological examination revealed that the natural process of repair of the osteochondral defects was promoted by 4 subcutaneous injections of intermediate-dose etanercept and by 1 or 4 injections of high-dose etanercept at the various time points examined postoperatively (4, 8, and 24 weeks). Western blot showed that rabbit TNFα had a high affinity for etanercept. Interpretation Blocking of TNF by etanercept enabled repair of osteochondral defects in rabbit knee. Anti-TNF therapy could be a strategy for the use of tissue engineering for bone and cartilage repair. PMID:19916697

  3. Induction of phospholipid-binding antibodies in mice and rabbits by immunization with human beta 2 glycoprotein 1 or anticardiolipin antibodies alone.

    PubMed Central

    Pierangeli, S S; Harris, E N

    1993-01-01

    Anticardiolipin (aCL) antibodies are autoantibodies present in high concentrations in patients with the antiphospholipid syndrome (APS), a disorder of recurrent thrombosis and pregnancy loss. What induces aCL antibodies is uncertain, but a recent report suggested that immunization of mice with beta 2 glycoprotein 1 (beta 2 GP1) in Freund's complete adjuvant (FCA) resulted in aCL antibody production in the recipient mice. Since this observation might explain how autoantibodies might be induced by poor immunogens, such as phospholipids, we decided to explore the question further. In our first series of experiments, we found that aCL antibodies were induced in mice by beta 2GP1 mixed with adjuvants that did not contain lipids (Adju-Prime or aluminium hydroxide). This excluded the possibility that antibody induction occurred because beta 2GP1 formed complexes with lipids in FCA. We also found that aCL antibodies always appeared before anti-beta 2GP1 antibodies, excluding the possibility that aCL antibodies were directed to beta 2GP1 or were induced by formation of anti-idiotypic antibodies (to anti-beta 2GP1). In experiments, we found that immunization of mice with human IgG antibodies from patients with the APS (IgG-APS), also induced aCL antibodies. Immunization with pure bovine serum albumin (BSA) did not induce aCL antibodies. We propose that aCL antibodies are induced by proteins with high avidity for phospholipids. These proteins may be bound to phospholipids when introduced, or may bind circulating phospholipids, so transforming phospholipid molecules into immunogens. Similar mechanisms might explain autoantibody induction to other poor immunogens. PMID:8348755

  4. Subunit interface mutants of rabbit muscle aldolase form active dimers.

    PubMed Central

    Beernink, P. T.; Tolan, D. R.

    1994-01-01

    We report the construction of subunit interface mutants of rabbit muscle aldolase A with altered quaternary structure. A mutation has been described that causes nonspherocytic hemolytic anemia and produces a thermolabile aldolase (Kishi H et al., 1987, Proc Natl Acad Sci USA 84:8623-8627). The disease arises from substitution of Gly for Asp-128, a residue at the subunit interface of human aldolase A. To elucidate the role of this residue in the highly homologous rabbit aldolase A, site-directed mutagenesis is used to replace Asp-128 with Gly, Ala, Asn, Gln, or Val. Rabbit aldolase D128G purified from Escherichia coli is found to be similar to human D128G by kinetic analysis, CD, and thermal inactivation assays. All of the mutant rabbit aldolases are similar to the wild-type rabbit enzyme in secondary structure and kinetic properties. In contrast, whereas the wild-type enzyme is a tetramer, chemical crosslinking and gel filtration indicate that a new dimeric species exists for the mutants. In sedimentation velocity experiments, the mutant enzymes as mixtures of dimer and tetramer at 4 degrees C. Sedimentation at 20 degrees C shows that the mutant enzymes are > 99.5% dimeric and, in the presence of substrate, that the dimeric species is active. Differential scanning calorimetry demonstrates that Tm values of the mutant enzymes are decreased by 12 degrees C compared to wild-type enzyme. The results indicate that Asp-128 is important for interface stability and suggest that 1 role of the quaternary structure of aldolase is to provide thermostability. PMID:7833800

  5. Microbiological quality of rabbit meat.

    PubMed

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

    2004-05-01

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

  6. Effects of raloxifene and alendronate on non-enzymatic collagen cross-links and bone strength in ovariectomized rabbits in sequential treatments after daily human parathyroid hormone (1-34) administration.

    PubMed

    Kimura, S; Saito, M; Kida, Y; Seki, A; Isaka, Y; Marumo, K

    2017-03-01

    This study investigated the effects of raloxifene and alendronate to follow parathyroid hormone (PTH) on bone collagen and biomechanical properties in ovariectomized rabbits. Sequential treatments of raloxifene and alendronate after hPTH(1-34) treatment improved biomechanical properties with and without bone collagen improvement, respectively.

  7. Expression of TRPV1 in rabbits and consuming hot pepper affects its body weight.

    PubMed

    Yu, Qi; Wang, Yanli; Yu, Ying; Li, Yafeng; Zhao, Sihai; Chen, Yulong; Waqar, Ahmed Bilal; Fan, Jianglin; Liu, Enqi

    2012-07-01

    The capsaicin receptor, known as transient receptor potential vanilloid subfamily member 1 (TRPV1), is an important membrane receptor that has been implicated in obesity, diabetes, metabolic syndrome and cardiovascular diseases. The rabbit model is considered excellent for studying cardiovascular and metabolic diseases, however, the tissue expression of TRPV1 and physiological functions of its ligand capsaicin on diet-induced obesity have not been fully defined in this model. In the current study, we investigated the tissue expression of TRPV1 in normal rabbits using real-time RT-PCR and Western blot analysis. Rabbit TRPV1 mRNA was highly expressed in a variety of organs, including the kidneys, adrenal gland, spleen and brain. A phylogenetic analysis showed that the amino acid sequence of rabbit TRPV1 was closer to human TRPV1 than rodent TRPV1. To examine the effect of capsaicin (a pungent compound in hot pepper) on body weight, rabbits were fed with either a high fat diet (as control) or high fat diet containing 1% hot pepper. We found that the body weight of the hot pepper-fed rabbits was significantly lower than the control group. We conclude that the intake of capsaicin can prevent diet-induced obesity and rabbit model is useful for the study of TRPV1 function in cardiovascular and metabolic diseases.

  8. HEREDITARY ACHONDROPLASIA IN THE RABBIT

    PubMed Central

    Pearce, Louise; Brown, Wade H.

    1945-01-01

    Pathological observations on hereditary achondroplasia in the rabbit have been described. At autopsy, the chief features of interest are: reduced size with disproportionately shortened extremities and large head, cutaneous and subcutaneous edema of variable degree and distribution, small shortened bones with a cartilaginous appearance and texture, immature teeth, and cleft palate in one-fourth the cases; blood-stained fluid in the thoracic and abdominal cavities; a comparatively small heart pointing to the right of the midline, a very large firm thymus, a large pale soft spleen, a large swollen liver with red mottling, and a stomach distended with thin greenish mucus but no milk. The mean relative weights of all organs in terms of the net body weight were larger than those of normal new-born litter mates. The mean actual weights of the kidneys, the brain, and especially the spleen and the thymus were also larger than their respective normal values, those of the heart, liver, and adrenals were slightly smaller, while that of the pituitary was the same. Histologically, all endochondral cartilages show marked abnormalities of differentiation with pronounced deficiency of ossification. Calcification of membranous bones is likewise deficient. The histological abnormalities of the long bones are very similar to, if not identical with, those characteristic of human fetal chondrodystrophy, the creeper fowl condition, the "bull-dog" calf, and achondroplasia of the dog. No histological evidence was found in any organ which would suggest a basis for a responsible causal agent of the abnormality. Minor to marked vascular dilatation and congestion and edema is a variable feature but is fairly widely distributed. The changes in the thyroid indicate an active gland. The cellular pattern of the pituitary is characterized by some increase in basophilic cells. The lymphoid elements of the spleen are more or less depleted. The hemopoietic tissue in the spleen and liver is reduced in

  9. Rabbits immunised with recombinant BCG expressing the cottontail rabbit papillomavirus (CRPV) L2E7E2 genes induces regression of established papillomas.

    PubMed

    Govan, V A; Williamson, A-L

    2007-07-01

    We previously demonstrated in a cottontail rabbit papillomavirus (CRPV) challenge model that recombinant Bacille Calmette-Guerin (rBCG) could potentially be used as a prophylactic vaccine vehicle to deliver papillomavirus proteins. In this study we investigated whether regression of CRPV-induced papillomas could be achieved following immunisation of out-bred New Zealand White rabbits with rBCG expressing CRPVL2, CRPVE2, CRPVE7 or CRPVL2E7E2 proteins. Rabbits immunised with rBCG/CRPVL2E7E2 had papillomas that were largely suppressed and were significantly smaller compared to the rBCG negative control group (Prabbits immunised with rBCG/CRPVL2E7E2 had papillomas that completely regressed 1.5 weeks post third immunisation. Rabbits immunised with rBCG/CRPVL2, rBCG/CRPVE7, or rBCG/CRPVE2 had papillomas that were significantly smaller than the negative control rabbits (Phuman papillomavirus proteins as a possible therapeutic vaccine.

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

    PubMed

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

    1997-02-01

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

  11. Transiently enhanced LPS-induced fever following hyperthermic stress in rabbits

    NASA Astrophysics Data System (ADS)

    Shibata, Masaaki; Uno, Tadashi; Riedel, Walter; Nishimaki, Michiyo; Watanabe, Kaori

    2005-11-01

    Hyperthermia has been shown to induce an enhanced febrile response to the bacterial-derived endotoxin lipopolysaccharide (LPS). The aim of the present study was to test the hypothesis that the enhanced LPS-induced fever seen in heat stressed (HS) animals is caused by leakage of intestinal bacterial LPS into the circulation. Male rabbits were rendered transiently hyperthermic (a maximum rectal temperature of 43°C) and divided into three groups. They were then allowed to recover in a room at 24°C for 1, 2 or 3 days post-HS. One day after injection with LPS, the post-HS rabbits exhibited significantly higher fevers than the controls, though this was not seen in rabbits at either 2 or 3 days post-HS. The plasma levels of endogenous LPS were significantly increased during the HS as compared to those seen in normothermic rabbits prior to HS. LPS fevers were not induced in these animals. One day post-HS, rabbits that had been pretreated with oral antibiotics exhibited significantly attenuated LPS levels. When challenged with human recombinant interleukin-1β instead of LPS, the 1-day post-HS rabbits did not respond with enhanced fevers. The plasma levels of TNFα increased similarly during LPS-induced fevers in both the control and 1-day post-HS rabbits, while the plasma levels of corticosterone and the osmolality of the 1-day post-HS rabbits showed no significant differences to those seen prior to the HS. These results suggest that the enhanced fever in the 1-day post-HS rabbits is LPS specific, and may be caused by increased leakage of intestinal endotoxin into blood circulation.

  12. Gene Expression Profiles in a Rabbit Model of Systemic Lupus Erythematosus Autoantibody Production1

    PubMed Central

    Rai, Geeta; Ray, Satyajit; Milton, Jacqueline; Yang, Jun; Ren, Ping; Lempicki, Richard; Mage, Rose G.

    2010-01-01

    We previously reported the establishment of a rabbit (Oryctolagus cuniculus) model in which peptide immunization led to production of lupus-like autoantibodies including anti-Sm, -RNP, -SS-A, -SS-B and –dsDNA characteristic of those produced in Systemic Lupus Erythematosus (SLE) patients. Some neurological symptoms in form of seizures and nystagmus were observed. The animals used in the previous and in the present study were from a National Institute of Allergy and Infectious Diseases colony of rabbits that were pedigreed, immunoglobulin allotype-defined but not inbred. Their genetic heterogeneity may correspond to that found among patients of a given ethnicity. We extended the information about this rabbit model by microarray based expression profiling. We first demonstrated that human expression arrays could be used with rabbit RNA to yield information on molecular pathways. We then designed a study evaluating gene expression profiles in 8 groups of control and treated rabbits (47 rabbits in total). Genes significantly upregulated in treated rabbits were associated with NK cytotoxicity, antigen presentation, leukocyte migration, cytokine activity, protein kinases, RNA spliceosomal ribonucleoproteins, intracellular signaling cascades, and glutamate receptor activity. These results link increased immune activation with up-regulation of components associated with neurological and anti-RNP responses, demonstrating the utility of the rabbit model to uncover biological pathways related to SLE-induced clinical symptoms, including Neuropsychiatric Lupus. Our finding of distinct gene expression patterns in rabbits that made anti-dsDNA compared to those that only made other anti-nuclear antibodies should be further investigated in subsets of SLE patients with different autoantibody profiles. PMID:20817871

  13. Transgenic Rabbits Expressing Ovine PrP Are Susceptible to Scrapie

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2014-02-04

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

  15. Sequence and diversity of rabbit T-cell receptor gamma chain genes

    SciTech Connect

    Isono, T.; Kim, C.J.; Seto, A.

    1995-03-01

    The nucleotide sequences of one constant (C), six variable (V), and two joining (J) gene segments coding for the rabbit T-cell receptor gamma chain (Tcrg) were determined by directly sequencing fragments amplified by the cassette-ligation mediated polymerase chain reaction. The Tcrg-C gene segment did not encode a cysteine residue for connection to the Tcr delta chain in the connecting region, and two variant forms of the Tcrg-C gene segment were generated by alternative splicing, like the human Tcrg-C2 gene. Five of six rabbit Tcrg-V gene segments belonged to the same family and displayed similarity to five productive human Tcrg-V1 family genes as well as the mouse Tcrg-V5 gene. The remaining rabbit Tcrg-V gene segment displayed similarity to the human Tcrg-V3 gene. Both rabbit Tcrg-J gene segments displayed similarity to the human Tcrg-J2.1 and 2.3, respectively. These findings suggested that the genomic organization of rabbit Tcrg genes is more similar to that of human than of mouse Tcrg genes. 18 refs., 4 figs., 1 tab.

  16. Hepatitis E vaccine immunization for rabbits to prevent animal HEV infection and zoonotic transmission.

    PubMed

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

    2015-09-11

    Hepatitis E virus (HEV) infection has become a significant global public health concern as increasing cases of acute and chronic hepatitis E are reported. HEV of animal origin was proved to be a possible source of human infection and a previous study showed that the recent licensed HEV 239 vaccine can serve as a candidate vaccine to manage animal sources of HEV infection. However, previous immunization strategy for rabbits was the same as that for human, which is too costly to conduct large-scale animal vaccination. In an effort to reduce the costs, three vaccination schemes were assessed in the present study. Forty specific pathogen-free (SPF) rabbits were divided randomly into five groups with eight animals for each and inoculated intramuscularly with different doses of HEV 239 and placebo, respectively. All animals were challenged intravenously with swine HEV-4 and rabbit HEV of different titers 7 weeks after the initial immunization and then fecal virus excretion was monitored for 10 weeks. The results indicated that immunizing rabbits with two 10μg doses of the vaccine is superior to vaccination with two 20μg doses or a single 30μg dose, which can protect rabbits against homologous and heterologous HEV infection. These findings could enable implementation of large-scale animal vaccination to prevent rabbit HEV infection and zoonotic transmission.

  17. The Rabbit Corneal Pocket Assay.

    PubMed

    Morbidelli, Lucia; Ziche, Marina

    2016-01-01

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

  18. The ABCG2 efflux transporter from rabbit placenta: Cloning and functional characterization.

    PubMed

    Halwachs, Sandra; Kneuer, Carsten; Gohlsch, Katrin; Müller, Marian; Ritz, Vera; Honscha, Walther

    2016-02-01

    In human placenta, the ATP-binding cassette efflux transporter ABCG2 is highly expressed in syncytiotrophoblast cells and mediates cellular excretion of various drugs and toxins. Hence, physiological ABCG2 activity substantially contributes to the fetoprotective placenta barrier function during gestation. Developmental toxicity studies are often performed in rabbit. However, despite its toxicological relevance, there is no data so far on functional ABCG2 expression in this species. Therefore, we cloned ABCG2 from placenta tissues of chinchilla rabbit. Sequencing showed 84-86% amino acid sequence identity to the orthologues from man, rat and mouse. We transduced the rabbit ABCG2 clone (rbABCG2) in MDCKII cells and stable rbABCG2 gene and protein expression was shown by RT-PCR and Western blot analysis. The rbABCG2 efflux activity was demonstrated with the Hoechst H33342 assay using the specific ABCG2 inhibitor Ko143. We further tested the effect of established human ABCG2 (hABCG2) drug substrates including the antibiotic danofloxacin or the histamine H2-receptor antagonist cimetidine on H33342 accumulation in MDCKII-rbABCG2 or -hABCG2 cells. Human therapeutic plasma concentrations of all tested drugs caused a comparable competitive inhibition of H33342 excretion in both ABCG2 clones. Altogether, we first showed functional expression of the ABCG2 efflux transporter in rabbit placenta. Moreover, our data suggest a similar drug substrate spectrum of the rabbit and the human ABCG2 efflux transporter.

  19. Rabbit serum albumin hydrolyzes the carbamate carbaryl.

    PubMed

    Sogorb, Miguel A; Carrera, Victoria; Benabent, Mónica; Vilanova, Eugenio

    2002-04-01

    One of the main detoxification processes of the carbamate insecticides is the hydrolysis of the carbamic ester bond. Carboxylesterases seem to play important roles in the metabolization of carbamates. This study performs a biochemical characterization of the capabilities of rabbit serum albumin (RSA) to hydrolyze the carbamate carbaryl. Rabbit serum albumin was able to hydrolyze carbaryl with a K(cat) of 7.1 x 10(-5) s(-1). The K(m) for this hydrolysis reaction was 240 microM. Human, chicken, and bovine serum albumins were also able to hydrolyze carbaryl. The divalent cation Cu(2+) at 1 mM concentration inhibited around 50% of the hydrolysis of carbaryl by RSA. Other mono- and divalent cations at 1 mM concentration and 5 mM EDTA exerted no significant effects on the hydrolysis of carbaryl by RSA. The inhibition of the carbaryl hydrolysis by sulfydril blocking agents suggests that a cysteine residue plays an important role in the active center of the catalytic activity. Both caprylic and palmitic acids were noncompetitive inhibitors of the carbaryl hydrolysis by RSA. The carboxyl ester p-nitrophenyl butyrate is a substrate of RSA and competitively inhibited the hydrolysis of carbaryl by this protein, suggesting that the hydrolysis of carbaryl and the hydrolysis of carboxyl esters occur in the same catalytic site and through a similar mechanism. This mechanism might be based on the carbamylation of a tyrosine residue of the RSA. Serum albumin is a protein universally present in nontarget species of insecticides; therefore, the capability of this protein to hydrolyze other carbamates must be studied because it might have important toxicological and ecotoxicological implications.

  20. Investigations of a rabbit (Oryctolagus cuniculus) model of systemic lupus erythematosus (SLE), BAFF and its receptors.

    PubMed

    Yang, Jiahui; Pospisil, Richard; Ray, Satyajit; Milton, Jacqueline; Mage, Rose G

    2009-12-30

    B-cell activation factor belonging to the tumor necrosis factor family (BAFF) is a major contributor to survival of B lymphocytes during development and maturation. A relationship between circulating BAFF levels and disease activity has been reported in patients with the autoimmune disease Systemic Lupus Erythematosus (SLE). Clinical trials targeting BAFF or its receptors are currently in progress. In order to further characterize a rabbit (Oryctolagus cuniculus) model of SLE, we investigated the expression of BAFF and its receptors in non-inbred, pedigreed rabbits derived from breeding and selection based on autoantibody responses. We immunized rabbits related to previous groups that developed autoantibodies and inflammatory responses after immunizations with peptides synthesized on multiple antigen-branched polylysine backbones. Blood and sera collected before immunization and after boosts were used for health monitoring, analyses of serum autoantibody responses by ELISA and immunofluorescence. Peripheral blood mononuclear cells (PBMC) were studied by flow cytometry and were the source of mRNA for quantitative PCR analyses. We hypothesized that BAFF mRNA expression and serum BAFF levels measured indirectly through BAFF receptor binding might increase in autoantibody-producing rabbits. Immunized rabbits developed elevated levels of leucocyte populations, anti-nuclear, anti-dsDNA and other autoantibodies. BR3 mRNA levels in total PBMC decreased and BAFF levels remained low and unchanged in most immunized rabbits. By flow cytometry, percentages of BAFF positive cells decreased. Percentages of transmembrane activator and CAML interactor (TACI) decreased in most rabbits from all the immunized groups. The rabbit is an important model for human autoimmune and infectious diseases, and a high quality draft rabbit genome assembly was recently completed. Human disease models developed in non-inbred pedigreed animals are better able to reflect the complexities of diseases

  1. Generation of hypoxanthine phosphoribosyltransferase gene knockout rabbits by homologous recombination and gene trapping through somatic cell nuclear transfer

    PubMed Central

    Yin, Mingru; Jiang, Weihua; Fang, Zhenfu; Kong, Pengcheng; Xing, Fengying; Li, Yao; Chen, Xuejin; Li, Shangang

    2015-01-01

    The rabbit is a common animal model that has been employed in studies on various human disorders, and the generation of genetically modified rabbit lines is highly desirable. Female rabbits have been successfully cloned from cumulus cells, and the somatic cell nuclear transfer (SCNT) technology is well established. The present study generated hypoxanthine phosphoribosyltransferase (HPRT) gene knockout rabbits using recombinant adeno-associated virus-mediated homologous recombination and SCNT. Gene trap strategies were employed to enhance the gene targeting rates. The male and female gene knockout fibroblast cell lines were derived by different strategies. When male HPRT knockout cells were used for SCNT, no live rabbits were obtained. However, when female HPRT+/− cells were used for SCNT, live, healthy rabbits were generated. The cloned HPRT+/− rabbits were fertile at maturity. We demonstrate a new technique to produce gene-targeted rabbits. This approach may also be used in the genetic manipulation of different genes or in other species. PMID:26522387

  2. Late degeneration in rabbit tissues after irradiation by heavy ions

    NASA Technical Reports Server (NTRS)

    Lett, J. T.; Cox, A. B.; Keng, P. C.; Lee, A. C.; Su, C. M.; Bergtold, D. S.

    1980-01-01

    Results are presented for investigations of the late effects of heavy-ion irradiation on rabbit tissues which were undertaken to assess the hazards associated with the long-term exposure of humans to heavy ions in space during such activities as the construction of solar power stations or voyages to Mars. White rabbits approximately six weeks old were exposed to various doses of collimated beams of 400-MeV/n Ne ions, 570 MeV/n Ar ions and Co-60 gamma rays directed through both eyes, and the responses of the various tissues (hair follicles, skin, cornea, lens, retina, Harderian glands, bone and forebrain) were examined. Proliferating tissues are found to exhibit high damage levels in the early and late periods following irradiation, while terminally differentiating tissues repond to radiation most intensely in the late period, years after irradiation, with no intermediate recovery. The results obtained from rabbits are used to predict the occurrence of late tissue degeneration in the central nervous system, terminally differentiating systems and stem cells of humans one or more decades following exposure to radiation levels anticipated during long-duration space flights. The studies also indicate that tissues may be prematurely aged in the sense that tissue life spans may be shortened without the development of malignancies.

  3. The E7 protein of the cottontail rabbit papillomavirus immortalizes normal rabbit keratinocytes and reduces pRb levels, while E6 cooperates in immortalization but neither degrades p53 nor binds E6AP

    SciTech Connect

    Ganzenmueller, Tina; Matthaei, Markus; Muench, Peter; Scheible, Michael; Iftner, Angelika; Hiller, Thomas; Leiprecht, Natalie; Probst, Sonja; Stubenrauch, Frank; Iftner, Thomas

    2008-03-15

    Human papillomaviruses (HPVs) cause cervical cancer and are associated with the development of non-melanoma skin cancer. A suitable animal model for papillomavirus-associated skin carcinogenesis is the infection of domestic rabbits with the cottontail rabbit papillomavirus (CRPV). As the immortalizing activity of CRPV genes in the natural target cells remains unknown, we investigated the properties of CRPV E6 and E7 in rabbit keratinocytes (RK) and their influence on the cell cycle. Interestingly, CRPV E7 immortalized RK after a cellular crisis but showed no such activity in human keratinocytes. Co-expressed CRPV E6 prevented cellular crisis. The HPV16 or CRPV E7 protein reduced rabbit pRb levels thereby causing rabbit p19{sup ARF} induction and accumulation of p53 without affecting cellular proliferation. Both CRPV E6 proteins failed to degrade rabbit p53 in vitro or to bind E6AP; however, p53 was still inducible by mitomycin C. In summary, CRPV E7 immortalizes rabbit keratinocytes in a species-specific manner and E6 contributes to immortalization without directly affecting p53.

  4. Elastic modulus and collagen organization of the rabbit cornea: epithelium to endothelium

    PubMed Central

    Thomasy, Sara M.; Krishna Raghunathan, Vijay; Winkler, Moritz; Reilly, Christopher M.; Sadeli, Adeline R.; Russell, Paul; Jester, James V.; Murphy, Christopher J.

    2013-01-01

    The rabbit is commonly used to evaluate new corneal prosthetics and study corneal wound healing. Knowledge of the stiffness of the rabbit cornea would better inform design and fabrication of keratoprosthetics and substrates with relevant mechanical properties for in vitro investigations of corneal cellular behavior. This study determined the elastic modulus of the rabbit corneal epithelium, anterior basement membrane (ABM), anterior and posterior stroma, Descemet’s membrane (DM) and endothelium using atomic force microscopy (AFM). In addition, three-dimensional collagen fiber organization of the rabbit cornea was determined using nonlinear optical high-resolution macroscopy. Elastic modulus as determined by AFM for each corneal layer was: epithelium 0.57 ± 0.29 kPa (mean ± SD), ABM 4.5 ± 1.2 kPa, anterior stroma 1.1 ± 0.6 kPa, posterior stroma 0.38 ± 0.22 kPa, DM 11.7 ± 7.4 kPa, and endothelium 4.1 ± 1.7 kPa. Biophysical properties, including elastic modulus, are unique for each layer of the rabbit cornea and are dramatically softer in comparison to the corresponding regions of the human cornea. Collagen fiber organization is also dramatically different between the two species with markedly less intertwining observed in the rabbit versus human cornea. Given that substratum stiffness considerably alters corneal cell behavior, keratoprosthetics that incorporate mechanical properties simulating the native human cornea may not elicit optimal cellular performance in rabbit corneas that have dramatically different elastic moduli. These data will allow for the design of substrates that better mimic the biomechanical properties of the corneal cellular environment. PMID:24084333

  5. Molecular characterization and antimicrobial susceptibility of Clostridium difficile isolated from rabbits raised for meat production.

    PubMed

    Drigo, Ilenia; Mazzolini, Elena; Bacchin, Cosetta; Tonon, Elena; Puiatti, Cinzia; Bano, Luca; Spigaglia, Patrizia; Barbanti, Fabrizio; Agnoletti, Fabrizio

    2015-12-31

    Clostridium difficile is an important cause of enteric disease in humans and animals. Recent studies demonstrated a genetic overlap between C. difficile isolated from animals and humans suggesting animals as possible reservoir for human pathogenic strains. This study was a preliminary investigation on the occurrence of C. difficile in rabbits raised in industrial holdings for food production and aimed to characterise isolates and estimate their antimicrobial susceptibility. C. difficile isolates were characterized by toxin profiles, toxinotyping and PCR-ribotyping. The MICs of six antibiotics were determined using E-test. Between 2007 and 2013, 285 industrial holdings (representing 40% of the national census) submitted rabbits to our laboratory for diagnostic purposes, among these holdings, groups of three to five post-weaned rabbits were sampled once by convenience. 1279 samples of caecal content were collected. The overall isolation rate of C. difficile from the enteric specimen was 3% (38/1279), with no difference among animals affected or not by enteric disorders. Among isolates 66% (25/38) were toxigenic. Sixteen different PCR-ribotypes (RTs) were identified. Among the toxigenic strains RT-014/020, RT-078 and RT-012 were found in at least three rabbit holdings. According to the ECOFF threshold, 82% (31/38) C. difficile isolates displayed a reduced susceptibility to at least one and 18% (7/38) to three tested antimicrobials. Rabbits are colonized by heterogeneous C. difficile ribotypes many of which are commonly isolated in humans. One third of isolates displayed a reduced susceptibility to MTZ, the first choice antimicrobial for human CDI treatment. According to our findings rabbits are a potential source of C. difficile for humans.

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

    SciTech Connect

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

    2008-08-15

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

  7. Monitoring of Venus transgenic cell migration during pregnancy in non-transgenic rabbits.

    PubMed

    Lipták, N; Hoffmann, O I; Kerekes, A; Iski, G; Ernszt, D; Kvell, K; Hiripi, L; Bősze, Z

    2017-04-01

    Cell transfer between mother and fetus were demonstrated previously in several species which possess haemochorial placenta (e.g. in humans, mice, rats, etc.). Here we report the assessment of fetal and maternal microchimerism in non-transgenic (non-TG) New Zealand white rabbits which were pregnant with transgenic (TG) fetuses and in non-TG newborns of TG does. The TG construct, including the Venus fluorophore cDNA driven by a ubiquitous cytomegalovirus enhancer, chicken ß-actin promoter (CAGGS), was previously integrated into the rabbit genome by Sleeping Beauty transposon system. Three different methods [fluorescence microscopy, flow cytometry and quantitative polymerase chain reaction (QPCR)] were employed to search for TG cells and gene products in blood and other tissues of non-TG rabbits. Venus positive peripheral blood mononuclear cells (PBMCs) were not detected in the blood of non-TG littermates or non-TG does by flow cytometry. Tissue samples (liver, kidney, skeletal and heart muscle) also proved to be Venus negative examined with fluorescence microscopy, while histology sections and PBMCs of TG rabbits showed robust Venus protein expression. In case of genomic DNA (gDNA) sourced from tissue samples of non-TG rabbits, CAGGS promoter-specific fragments could not be amplified by QPCR. Our data showed the lack of detectable cell transfer between TG and non-TG rabbits during gestation.

  8. Disposition of glycolic acid into rat and rabbit embryos in vitro.

    PubMed

    Ellis-Hutchings, Robert G; Moore, Nigel P; Marshall, Valerie A; Rasoulpour, Reza J; Carney, Edward W

    2014-07-01

    High dose gavage administration of ethylene glycol (EG) induces teratogenicity in rodents, but not in rabbits, resulting from saturation of intermediate EG metabolism and glycolic acid (GA) accumulation. In vivo, rat embryos sequester GA 2-4-fold higher than maternal blood, a phenomenon absent in rabbits and proposed not to occur in humans. This research explored the mechanisms of GA disposition into rat and rabbit conceptuses using whole embryo culture (WEC). Rat and rabbit embryos concentrated GA from the culture medium. In vitro to in vivo discordance in the rabbit plausibly stemmed from anatomical differences between these models. GA sequestration was attenuated at 4°C in both species. Rat embryos further demonstrated pH-dependence of GA sequestration and inhibition by D-lactic acid. These data suggest GA disposition into rat and rabbit embryos is energy- and pH-dependent, and carrier-mediated. Anatomical and maternal-to-conceptal pH gradient differences likely underlie the lack of enhanced GA disposition in non-rodent species.

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

    PubMed

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

    2001-01-01

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

  10. Molecular Characterization of Enterocytozoon bieneusi in Domestic Rabbits (Oryctolagus cuniculus) in Northeastern China

    PubMed Central

    Zhang, Xiao-Xuan; Jiang, Jing; Cai, Ya-Nan; Wang, Chun-Feng; Xu, Peng; Yang, Gui-Lian; Zhao, Quan

    2016-01-01

    A study of 426 rabbits from 3 cities in Jilin province (Changchun City and Jilin City) and Liaoning province (Shenyang City) was conducted between May and June 2015. The overall prevalence of E. bieneusi in rabbits was 0.94% (4/426), with 0% (0/116), 1.72% (3/174), and 0.74% (1/136) in Jilin, Changchun, and Shenyang City, respectively. Only 3 farms (farm 1 and farm 3 in Changchun City, farm 8 in Shenyang City) were PCR-positive for E. bieneusi. Moreover, rabbits of more than 6 months (1.72%) had the highest E. bieneusi prevalence, followed by rabbits of 4-6 months (1.26%), 2-3 months (0.58%), and less than 1 month (0%). Analysis of ITS gene of E. bieneusi suggested that all 4 E. bieneusi isolates were genotype D, and were classified as group 1a. The present results first demonstrated the existence of zoonotic E. bieneusi in domestic rabbits in China. Effective control measures should be implemented to prevent E. bieneusi infection in domestic rabbits, other animals, and humans. PMID:26951984

  11. IMMUNIZATION OF RABBITS TO INFECTIOUS PAPILLOMATOSIS

    PubMed Central

    Shope, Richard E.

    1937-01-01

    Two intraperitoneal injections of either infectious or non-infectious rabbit papilloma suspensions actively immunize rabbits against papillomatosis. The capacity of the non-infectious suspensions to immunize is considered as evidence that they contain papilloma virus even though none can be demonstrated by the usual infection test. PMID:19870596

  12. Carbon monoxide-releasing molecule-2 enhances coagulation in rabbit plasma and decreases bleeding time in clopidogrel/aspirin-treated rabbits.

    PubMed

    Nielsen, Vance G; Chawla, Nikhil; Mangla, Dipty; Gomes, Sheldon B; Arkebauer, Matthew R; Wasko, Kimberly A; Sadacharam, Kesavan; Vosseller, Keith

    2011-12-01

    Administration of carbon monoxide derived from carbon monoxide-releasing molecules has been demonstrated to enhance coagulation in vitro at small concentrations (100-200 μmol/l) in human and rabbit plasma. We sought to determine if carbon monoxide-releasing molecule-2 [tricarbonyldichlororuthenium (II) dimer, CORM-2] would improve coagulation in rabbit plasma in vitro via thrombelastography and in an in vivo preclinical rabbit model of ear bleeding time following administration of clopidogrel (20 mg/kg) with aspirin (10 mg/kg) via gavage. Addition of 100 μmol/l CORM-2 to rabbit plasma significantly improved coagulation. This procoagulant effect was blocked by pre-exposure of plasma to an agent that converts hemefibrinogen to methemefibrinogen in human plasma, preventing carbon monoxide binding and enhancement of coagulation. Rabbit ear bleeding time was 5.8 ± 1.1 min 2-3 h after clopidogrel/aspirin administration. Bleeding time significantly decreased to 2.6 ± 0.6 min, 5 min after administration of CORM-2 (10 mg/kg; 279 μmol/l 'best-case' instantaneous concentration) intravenously. CORM-2 enhances plasmatic coagulation in a manner similar to that of human plasma in vitro, and plasmatic coagulation is enhanced in vivo by CORM-2 as well. Additional preclinical investigation of the effects of CORM-2 on coagulopathy (e.g. heparin or hemodilution mediated) utilizing this rabbit model is planned.

  13. Prevalence and types of hyponatraemia, its relationship with hyperglycaemia and mortality in ill pet rabbits.

    PubMed

    Bonvehi, C; Ardiaca, M; Barrera, S; Cuesta, M; Montesinos, A

    2014-05-31

    Prevalence of hyponatraemia has not been extensively studied in pet rabbits, and the reference data for calculated plasma tonicity and osmolarity are not available. This retrospective clinical study reports the prevalence of hyponatraemia, hyposmolarity and hypotonicity in ill pet rabbits (n=356). The relationship between sodium and glucose levels was studied (n=134). Mortality rates within seven days associated with different sodium levels were calculated in ill rabbits (n=322). Venous blood samples in lithium heparin were processed using iStat EC8+ cartridges. The 95% RI for plasma sodium, calculated osmolarity and tonicity from 51 healthy pet rabbits were 136-147 mEq/l, 284-312 mOsm/l and 278-302 mOsm/l, respectively. The prevalence of hyponatraemia, hypotonicity and hyposmolarity was 39.0 per cent, 28.7 per cent and 18.0 per cent, respectively. Pseudohyponatraemia was present in 28.1 per cent and true hyponatraemia was present in 71.9 per cent of the cases of hyponatraemia. Sodium levels less than 129 mEq/l were found to be associated with 2.3-fold increase in mortality risk. Plasmatic sodium levels in rabbits decrease in conditions of hyperglycaemia in a similar manner as it occurs in human beings. As hyperglycaemia is quite a common condition in rabbits, simultaneous measurement of plasmatic sodium along with glucose in ill rabbits is advised. Hyponatraemia is a common condition in ill rabbits and, depending on its type (true hyponatraemia or pseudohyponatraemia), of varying clinical relevance. Calculation of plasmatic tonicity is necessary for differentiation of types of hyponatraemia.

  14. Thermal cataract formation in rabbits

    SciTech Connect

    Kramar, P.; Harris, C.; Guy, A.W.

    1987-01-01

    Intraocularly circulating hot water was used to produce cataracts in nine eyes of seven rabbits by maintaining their retrolental temperatures between 43 degrees C and 45 degrees C. A rapid rate of heating (1.3 degrees C/min) plus a sharp temperature gradient across the eye may have been contributing factors in the consistent production of cataracts at these temperatures. Biomicroscopy and light microscopy showed lens changes similar to those associated with acute exposure to microwave radiation. These findings support the assumption that microwave cataractogenesis is due to the local production of elevated temperatures.

  15. Novel Calicivirus Identified in Rabbits, Michigan, USA

    PubMed Central

    Wise, Annabel G.; Bolin, Steven R.; Mullaney, Thomas P.; Kiupel, Matti; Maes, Roger K.

    2009-01-01

    We report a disease outbreak in a Michigan rabbitry of a rabbit calicivirus distinct from the foreign animal disease agent, rabbit hemorrhagic disease virus (RHDV). The novel virus has been designated Michigan rabbit calicivirus (MRCV). Caliciviruses of the Lagovirus genus other than RHDV have not been described in US rabbit populations. The case-fatality rate was 32.5% (65/200). Clinical signs included hemorrhage and sudden death, with hepatic necrosis. Analysis of viral RNA sequence from >95% of the viral genome showed an average similarity of 79% with RHDV. Similarity of the predicted MRCV capsid amino acid sequence ranged from 89.8% to 91.3%, much lower than the 98% amino acid similarity between RHDV strains. Experimentally infected rabbits lacked clinical disease, but MRCV was detected in tissues by PCR. We propose that MRCV primarily causes subclinical infection but may induce overt RHD-like disease under certain field conditions. PMID:19961675

  16. Enzymatic Modification of Plasma Low Density Lipoproteins in Rabbits: A Potential Treatment for Hypercholesterolemia

    NASA Astrophysics Data System (ADS)

    Labeque, Regine; Mullon, Claudy J. P.; Ferreira, Joao Paulo M.; Lees, Robert S.; Langer, Robert

    1993-04-01

    Phospholipase A_2 (EC 3.1.1.4) hydrolyzes certain phospholipids of low density lipoprotein (LDL). Plasma clearance of phospholipase A_2-modified human LDL is up to 17 times faster than that of native human LDL in hypercholesterolemic rabbits. Modification of blood lipoproteins of hypercholesterolemic rabbits was performed by using an extracorporeal circuit containing immobilized phospholipase A_2. After 90-min treatments, nearly 30% decreases in plasma cholesterol concentrations were observed. Erythrocyte, leukocyte, and platelet counts showed no net change after treatment. This technique does not require any fluid replacement or sorbent regeneration and offers a potential approach for lowering serum cholesterol and LDL levels.

  17. Behavioral fever in newborn rabbits

    NASA Technical Reports Server (NTRS)

    Satinoff, E.; Mcewen, G. N., Jr.; Williams, B. A.

    1976-01-01

    New Zealand white rabbit pups aged 12 to 72 hr were divided into three groups and given an intraperitoneal injection of Pseudomonas polysaccharide, a saline vehicle alone, and no treatment, respectively. The animals injected with pyrogen and maintained at an ambient temperature of 32 C for 2 hr did not develop fever. When placed in a thermally graded alleyway, the animals injected with pyrogen selected gradient positions that represented significantly higher temperatures than controls injected with saline. Further stay at selected positions for 5 min caused a considerable increase in the rectal temperature of the pyrogen-injected pups but not that of controls. The results support the hypothesis that newborn rabbits will develop a fever by behavioral means after a single injection of an exogenous pyrogen if the opportunity for thermoregulatory behavior is present. No fever develops if the pups must rely solely on internal thermoregulatory mechanisms. The behavioral system for producing a fever is mature at birth, but an adequate system of internal reflexes does not appear to develop for some days.

  18. Biochemical investigation of cypermethrin toxicity in rabbits.

    PubMed

    Dahamna, S; Harzallah, D; Guemache, A; Sekfali, N

    2009-01-01

    Pyrethroids are the most frequently used pesticides in agriculture, forestry, horticulture, hospitals public health, homes and textile industry. Cypermethrin, a composite pyrethroid is moderately toxic to mammals. Exposure to the pyrethroids occurs by inhalation, dermal and oral routes both accidentally as well as from the environment. Cypermethrin and DDT have been detected in human breast milk from malaria endemic area in South Africa. The WHO has recommended that the level of permethrin in drinking water not exceed 20 micrograms per liter (microg/L). The effects of exposure to any hazardous substance depend on the dose, the duration, how you are exposed, personal traits, habits and whether other chemicals are present. Pyrethroids are often combined commercially with other chemicals called synergists, which enhance the insecticidal activity of the pyrethrins and pyrethroids. The synergists prevent some enzymes from breaking down the pyrethrins and pyrethroids, thus increasing their toxicity. Because these compounds are broken down in the body quickly, there are several ways to measure the metabolites of these chemicals in human blood and urine. In this study the pyrethroid cypermethrin Sherpa 25% (active substance 250 g/l cypermethrin) was used, rabbits (1 kg weight), were gavaged by 1/20 LD50 for 3 weeks (one dose every week). Blood was collected before dosing and after 24, 72, 144 hours after the treatment. Enzyme activities were assayed in the plasma samples obtained. GOT, GPT, ALPH, CREA, GGT, Glucose and Total Pro were measured. Rabbits showed depression, decrease in feed intake, body weight and loose faeces. Livers exhibited fatty change, necrosis, lesions in kidney included tubular necrosis and pink homogeneous tubular casts. Serum ALT and creatinine concentrations increased while those of total proteins, albumin, serum cholesterol and triglycerides decreased.The results showed a decrease in RBC; WBC and Hb. This probably explained by the effect of

  19. Chitosan prevents adhesion during rabbit flexor tendon repair via the sirtuin 1 signaling pathway.

    PubMed

    Chen, Qiang; Lu, Hui; Yang, Hu

    2015-09-01

    Chitosan has been demonstrated to exert potent anti-adhesive activity during tendon repair; however, the underlying molecular mechanisms remain unclear. The present study aimed to investigate the preventive effects of chitosan on adhesion in rabbit tendon repair, and to investigate the role of the sirtuin (SIRT)1 signaling pathway in this process. A total of 30 rabbits were divided randomly into three equal groups: Group 1, saline treatment; group 2, chitosan treatment; and group 3, chitosan + nicotinamide treatment. The flexor tendon of each of the rabbits was injured, and subsequently each rabbit was injected with the one of the reagents. Six weeks post‑surgery, all of the rabbits were sacrificed and their flexor tendons were harvested for subsequent evaluation of adhesion. Western blotting was used to determine the protein expression levels of specific signaling molecules. An MTT assay was conducted to evaluate the viability of human tenocytes and flow cytometry was used to analyze the apoptotic rate of the cells. The present study demonstrated that treatment with chitosan relieved adhesion in the rabbits with flexor tendon injuries. In addition, chitosan treatment increased SIRT1 expression, and reduced acetylated p65 and p53 expression in the tendons. The effects of chitosan on the tendons were attenuated by treatment with nicotinamide (a SIRT1 inhibitor). In the human tenocytes, pretreatment with chitosan resulted in an inhibition of interleukin (IL)‑1β‑induced apoptosis. Furthermore, chitosan reversed the IL‑1β‑induced downregulation of SIRT1 and upregulation of acetylated p65 and p53. Furthermore, downregulation of Sirt1 by RNA interference abrogated the effects of chitosan on the levels of p65 and p53 acetylation, and the rate of tenocyte apoptosis. In conclusion, chitosan treatment prevented adhesion via the SIRT1 signaling pathway during rabbit flexor tendon repair. These results indicate that SIRT1 may be targeted for therapeutic

  20. 9 CFR 354.124 - Quarantine of diseased rabbits.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Quarantine of diseased rabbits. 354... INSPECTION AND CERTIFICATION VOLUNTARY INSPECTION OF RABBITS AND EDIBLE PRODUCTS THEREOF Inspection Procedures; Ante-Mortem Inspections § 354.124 Quarantine of diseased rabbits. If live rabbits, which...

  1. 9 CFR 354.124 - Quarantine of diseased rabbits.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Quarantine of diseased rabbits. 354... INSPECTION AND CERTIFICATION VOLUNTARY INSPECTION OF RABBITS AND EDIBLE PRODUCTS THEREOF Inspection Procedures; Ante-Mortem Inspections § 354.124 Quarantine of diseased rabbits. If live rabbits, which...

  2. 9 CFR 354.124 - Quarantine of diseased rabbits.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Quarantine of diseased rabbits. 354... INSPECTION AND CERTIFICATION VOLUNTARY INSPECTION OF RABBITS AND EDIBLE PRODUCTS THEREOF Inspection Procedures; Ante-Mortem Inspections § 354.124 Quarantine of diseased rabbits. If live rabbits, which...

  3. 9 CFR 354.124 - Quarantine of diseased rabbits.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Quarantine of diseased rabbits. 354... INSPECTION AND CERTIFICATION VOLUNTARY INSPECTION OF RABBITS AND EDIBLE PRODUCTS THEREOF Inspection Procedures; Ante-Mortem Inspections § 354.124 Quarantine of diseased rabbits. If live rabbits, which...

  4. Increased expression of apolipoprotein E in transgenic rabbits results in reduced levels of very low density lipoproteins and an accumulation of low density lipoproteins in plasma.

    PubMed Central

    Fan, J; Ji, Z S; Huang, Y; de Silva, H; Sanan, D; Mahley, R W; Innerarity, T L; Taylor, J M

    1998-01-01

    Transgenic rabbits expressing human apo E3 were generated to investigate mechanisms by which apo E modulates plasma lipoprotein metabolism. Compared with nontransgenic littermates expressing approximately 3 mg/dl of endogenous rabbit apo E, male transgenic rabbits expressing approximately 13 mg/dl of human apo E had a 35% decrease in total plasma triglycerides that was due to a reduction in VLDL levels and an absence of large VLDL. With its greater content of apo E, transgenic VLDL had an increased binding affinity for the LDL receptor in vitro, and injected chylomicrons were cleared more rapidly by the liver in transgenic rabbits. In contrast to triglyceride changes, transgenic rabbits had a 70% increase in plasma cholesterol levels due to an accumulation of LDL and apo E-rich HDL. Transgenic and control LDL had the same binding affinity for the LDL receptor. Both transgenic and control rabbits had similar LDL receptor levels, but intravenously injected human LDL were cleared more slowly in transgenic rabbits than in controls. Changes in lipoprotein lipolysis did not contribute to the accumulation of LDL or the reduction in VLDL levels. These observations suggest that the increased content of apo E3 on triglyceride-rich remnant lipoproteins in transgenic rabbits confers a greater affinity for cell surface receptors, thereby increasing remnant clearance from plasma. The apo E-rich large remnants appear to compete more effectively than LDL for receptor-mediated binding and clearance, resulting in delayed clearance and the accumulation of LDL in plasma. PMID:9593771

  5. Factors affecting rabbit meat consumption among Spanish university students.

    PubMed

    González-Redondo, Pedro; Mena, Yolanda; Fernández-Cabanás, Victor M

    2010-01-01

    This study investigates the rabbit meat consumption patterns among students. Results of the 342 students surveyed at the University of Seville, Spain showed that more men than women consumed rabbit meat. More students consumed wild rabbit meat than farmed rabbit meat. The practice of hunting by students or their relatives, and the raising of rabbits for self-consumption, positively influenced the proportion of students that currently consumed rabbit meat. Most of the students that had eaten rabbit meat before but are currently non-eaters do so because of the meat's organoleptic characteristics or from lack of consumption habit.

  6. Economic and Quality of Life Benefits of Anti-VEGF Therapy.

    PubMed

    Hodgson, Nickisa; Wu, Frances; Zhu, Jie; Wang, Wenqui; Ferreyra, Henry; Zhang, Kang; Wang, Jiawei

    2016-09-06

    Vision impairment and blindness create a significant impact on quality of life and loss of productivity. Health care expenditures for vision problems, including direct medical costs and indirect costs for support services and loss of productivity, amount to $139 billion annually. It is projected that by 2020, five million people will have visual impairment due to age related macular degeneration and diabetic macular edema. VEGF inhibitor therapy has been shown to be a cost-effective treatment for age related macular degeneration and diabetic macular edema that has reduced the incidence of vision loss and can reduce the associated economic and societal cost.

  7. New paradigms in the treatment of wet AMD: the impact of anti-VEGF therapy.

    PubMed

    Menon, G; Walters, G

    2009-03-01

    The incidence of age-related macular degeneration (AMD) in the United Kingdom is increasing with the ageing population. The wet form of this progressive and potentially blinding disease can develop very rapidly and lead to severe loss of central vision and reduction in quality of life, sometimes in just a matter of weeks. Recent advances in the treatment of wet AMD with the licensing of anti-vascular endothelial growth factor therapies, coupled with current guidance from the Scottish Medicines Consortium and the National Institute of Health and Clinical Excellence have led to a subsequent increase in workload at AMD clinics due to the increased number of patients now eligible for treatment. In addition, the Royal College of Ophthalmologists recommend a 2-week diagnosis to treatment schedule due to the aggressive nature of the disease. The role of the retinal specialist is thus changing, and business management skills are becoming increasingly necessary to obtain the necessary resources to implement the guidance. Through prior experience and formal external evaluation of services at Frimley Park and Harrogate District Hospitals, a number of critical success factors have been developed for optimising treatment pathways in efficient wet AMD clinics.

  8. Anti-VEGF treatment and peripheral retinal nonperfusion in patients with central retinal vein occlusion

    PubMed Central

    Abri Aghdam, Kaveh; Reznicek, Lukas; Soltan Sanjari, Mostafa; Klingenstein, Annemarie; Kernt, Marcus; Seidensticker, Florian

    2017-01-01

    Purpose To evaluate the association between the size of peripheral retinal nonperfusion and the number of intravitreal ranibizumab injections in patients with treatment-naïve central retinal vein occlusion (CRVO). Methods Fifty-four patients with treatment-naïve CRVO and macular edema were included. Each patient underwent a full ophthalmologic examination including optical coherence tomography imaging and ultrawide-field fluorescein angiography. Monthly intravitreal ranibizumab injections were applied according to the recommendations of the German Ophthalmologic Society. Two ophthalmologists quantified the areas of peripheral retinal nonperfusion (group 1= less than five disc areas, group 2= more than five disc areas). Correlation analyses between the size of nonperfusion with best-corrected visual acuity, central subfield thickness, and the number of intravitreal injections were performed. Results Best-corrected visual acuity improved significantly after intravitreal injections (P<0.001, both groups). Final central subfield thickness after treatment did not significantly differ between both groups (P=0.92, P=0.96, respectively). Mean number of injections in group 1 and group 2 was 4.12±2.73 and 9.32±3.84, respectively (P<0.001). There was a significant positive correlation between areas of nonperfusion and the number of injections in each group. (R=0.97, P<0.001; R=0.94, P<0.001, respectively). Conclusion Peripheral retinal nonperfusion in patients with CRVO correlates significantly with the number of needed intravitreal ranibizumab injections. Ultrawide-field fluorescein angiography is a useful tool for detection of peripheral retinal ischemia, which may have direct implications in the diagnosis, follow-up, and treatment of these patients. PMID:28243056

  9. Effective electrophoretic mobilities and charges of anti-VEGF proteins determined by capillary zone electrophoresis.

    PubMed

    Li, S Kevin; Liddell, Mark R; Wen, He

    2011-06-01

    Macromolecules such as therapeutic proteins currently serve an important role in the treatment of eye diseases such as wet age-related macular degeneration and diabetic retinopathy. Particularly, bevacizumab and ranibizumab have been shown to be effective in the treatment of these diseases. Iontophoresis can be employed to enhance ocular delivery of these macromolecules, but the lack of information on the properties of these macromolecules has hindered its development. The objectives of the present study were to determine the effective electrophoretic mobilities and charges of bevacizumab, ranibizumab, and model compound polystyrene sulfonate (PSS) using capillary zone electrophoresis. Salicylate, lidocaine, and bovine serum albumin (BSA), which have known electrophoretic mobilities in the literature, were also studied to validate the present technique. The hydrodynamic radii and diffusion coefficients of BSA, bevacizumab, ranibizumab, and PSS were measured by dynamic light scattering. The effective charges were calculated using the Einstein relation between diffusion coefficient and electrophoretic mobility and the Henry equation. The results show that bevacizumab and ranibizumab have low electrophoretic mobilities and are net negatively charged in phosphate buffered saline (PBS) of pH 7.4 and 0.16M ionic strength. PSS has high negative charge but the electrophoretic mobility in PBS is lower than that expected from the polymer structure. The present study demonstrated that capillary electrophoresis could be used to characterize the mobility and charge properties of drug candidates in the development of iontophoretic drug delivery.

  10. Anti-VEGF therapy in a silicone oil-filled myopic eye with choroidal neovascularisation

    PubMed Central

    Chhablani, Jay; Narayanan, Raja

    2015-01-01

    A 33-year-old man presented with vision loss in his right eye due to rhegmatogenous retinal detachment, for which he underwent pars plana vitrectomy with silicone oil injection. Three months later, the patient presented with sudden vision loss. On examination, his visual acuity was 20/200 with presence of subretinal haemorrhage with attached retina and silicone oil in situ. Fluorescein angiography confirmed the diagnosis of choroidal neovascularisation (CNV). The patient underwent intravitreal ranibizumab injection (0.5 mg per 0.05 mL). He subsequently underwent oil removal along with intravitreal bevacizumab injection (1.25 mg per 0.05 mL). The CNV completely regressed. At 7 years follow-up, the patient's best corrected visual acuity was 20/50 with attached retina and macular scar due to regressed CNV. His other eye was within normal limits throughout the follow-up period. This unique case demonstrates the successful outcome of intravitreal ranibizumab injection in a silicone oil-filled eye with myopic CNV. PMID:25870215

  11. Effective Electrophoretic Mobilities and Charges of Anti-VEGF Proteins Determined by Capillary Zone Electrophoresis

    PubMed Central

    Li, S. Kevin; Liddell, Mark R.; Wen, He

    2011-01-01

    Macromolecules such as therapeutic proteins currently serve an important role in the treatment of eye diseases such as wet age-related macular degeneration and diabetic retinopathy. Particularly, bevacizumab and ranibizumab have been shown to be effective in the treatment of these diseases. Iontophoresis can be employed to enhance ocular delivery of these macromolecules, but the lack of information on the properties of these macromolecules has hindered its development. The objectives of the present study were to determine the effective electrophoretic mobilities and charges of bevacizumab, ranibizumab, and model compound polystyrene sulfonate (PSS) using capillary zone electrophoresis. Salicylate, lidocaine, and bovine serum albumin (BSA), which have known electrophoretic mobilities in the literature, were also studied to validate the present technique. The hydrodynamic radii and diffusion coefficients of BSA, bevacizumab, ranibizumab, and PSS were measured by dynamic light scattering. The effective charges were calculated using the Einstein relation between diffusion coefficient and electrophoretic mobility and the Henry equation. The results show that bevacizumab and ranibizumab have low electrophoretic mobilities and are net negatively charged in phosphate buffered saline (PBS) of pH 7.4 and 0.16 M ionic strength. PSS has high negative charge but the electrophoretic mobility in PBS is lower than that expected from the polymer structure. The present study demonstrated that capillary electrophoresis could be used to characterize the mobility and charge properties of drug candidates in the development of iontophoretic drug delivery. PMID:21269789

  12. Preclinical evaluation of holmium-166 labeled anti-VEGF-A(Bevacizumab).

    PubMed

    Khorami-Moghadam, Alireza; Bolouri, Bahram; Jalilian, Amir Reza; Bahrami-Samani, Nariman Mosafa Ali; Mazidi, Seyed Mohammad; Alirezapour, Behrouz

    2013-06-30

    Radiolabeled antiangiogenic monoclonal antibodies are potential agents for targeted therapy in specific types of malignancies. In this study, (166)Ho-DOTA-Bevacizumab was used in biodistribution studies using single-photon emission computed tomography (SPECT) to acquire dosimetric aspects of the radiolabeled antibody in mice. The liver toxicity of the radiolabeled antibody was also determined using serum glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase and alkaline phosphatase assay 2-7 days post-injection. The SPECT biodistribution demonstrated a similar pattern as the other radiolabeled anti-vascular endothelial growth factor A (VEGF-A) immunoconjugates. (166)Ho-DOTA-Bevacizumab was revealed as a potential compound for therapy/imaging of VEGF-A expression in oncology.

  13. Encephalitozoon cuniculi in rabbits: Serological screening and histopathological findings.

    PubMed

    Maestrini, Giovanni; Ricci, Emanuele; Cantile, Carlo; Mannella, Riccardo; Mancianti, Francesca; Paci, Gisella; D'Ascenzi, Carlo; Perrucci, Stefania

    2017-02-01

    Serological prevalence of E. cuniculi infection was assessed in 183 rabbits from central Italy. In seropositive deceased rabbits, histopathological lesions were also evaluated. Sera from 118 rabbits from 6 intensive farms, 10 rabbits from 6 family farms, 16 rabbits from a zoo, 30 rabbits from 5 research laboratories and 9 pet rabbits from 9 different owners, were tested by an enzyme-linked immunosorbent assay. Data were statistically analysed. Tissue samples from brain and kidney of 10 deceased rabbits were formalin-fixed and subsequently analysed by histopathology and immunohistochemistry. Anti-E. cuniculi antibodies were found in 129/183 (70.5%) analysed sera. At statistical analysis, E. cuniculi seropositivity was significantly higher (p<0.05) in industrial and zoo rabbits. At histology, different degrees of pathological lesions were found in serological positive (9) deceased animals. In three rabbits deceased after showing neurological signs, the severity of the lesions was interpreted as a likely cause for their death.

  14. The immunology of experimental Chagas' disease. IV. Production of lesions in rabbits similar to those of chronic Chagas' disease in man.

    PubMed Central

    Teixeira, A. R.; Teixeira, M. L.; Santos-Buch, C. A.

    1975-01-01

    Eight rabbits that received a single inoculation of trypomastigotes of a virulent strain of Trypanosoma cruzi first developed a transient acute illness associated with parasitemia; later, 4 of these rabbits died with chronic myocarditis and/or with megacolon in the absence of demonstrable parasitemia or encysted parasites in tissues. Two of these rabbits with chronic myocarditis died unexpectedly. Three of the inoculated rabbits that survived the infection were sacrificed 18 months later and showed similar but less severe microscopic lesions. The remaining rabbit is alive and well at the time of writing (26 months) with negative blood cultures but high hemagglutinating antibody titers to T. cruzi antigens. The natural course of T. cruzi infection in rabbits and the lesions observed postmortem are similar to those recorded for humans with chronic Chagas' disease. Multiple injections of particulate subcellular antigens of T. cruzi in rabbits resulted in microscopic lesions similar to those observed in rabbits that survived protozoan infection. Sera of rabbits inoculated with T. cruzi have antibodies to striated and smooth muscle structures. However, evidence provided in this and in other experiments strongly suggest that the lesions of chronic Chagas' disease are produced by delayed hypersensitivity to T. cruzi antigens. Images Figure 1 Figure 2 Figures 3-4 Figure 5 Figure 6 Figure 7 PMID:808136

  15. Bobcat attack on a cottontail rabbit

    USGS Publications Warehouse

    Biggins, D.E.; Biggins, D.M.

    2006-01-01

    We observed an attack by a bobcat (Lynx rufus) on a cottontail rabbit (Sylvilagus) that involved stealthy approach by the cat for >1 h, followed by a 12.3-s chase covering 116.0 m for the cat and 128.4 m for the rabbit. During the chase, the route of the cat from starting point to kill site was more direct than the semi-circular route of the rabbit. Stride lengths for the cat and total distance covered by the chase were longer than those previously reported for bobcats.

  16. Purification and Biochemical Characterisation of Rabbit Calicivirus RNA-Dependent RNA Polymerases and Identification of Non-Nucleoside Inhibitors

    PubMed Central

    Urakova, Nadya; Netzler, Natalie; Kelly, Andrew G.; Frese, Michael; White, Peter A.; Strive, Tanja

    2016-01-01

    Rabbit haemorrhagic disease virus (RHDV) is a calicivirus that causes acute infections in both domestic and wild European rabbits (Oryctolagus cuniculus). The virus causes significant economic losses in rabbit farming and reduces wild rabbit populations. The recent emergence of RHDV variants capable of overcoming immunity to other strains emphasises the need to develop universally effective antivirals to enable quick responses during outbreaks until new vaccines become available. The RNA-dependent RNA polymerase (RdRp) is a primary target for the development of such antiviral drugs. In this study, we used cell-free in vitro assays to examine the biochemical characteristics of two rabbit calicivirus RdRps and the effects of several antivirals that were previously identified as human norovirus RdRp inhibitors. The non-nucleoside inhibitor NIC02 was identified as a potential scaffold for further drug development against rabbit caliciviruses. Our experiments revealed an unusually high temperature optimum (between 40 and 45 °C) for RdRps derived from both a pathogenic and a non-pathogenic rabbit calicivirus, possibly demonstrating an adaptation to a host with a physiological body temperature of more than 38 °C. Interestingly, the in vitro polymerase activity of the non-pathogenic calicivirus RdRp was at least two times higher than that of the RdRp of the highly virulent RHDV. PMID:27089358

  17. Metabolism of hydroanthracenones in rabbits

    PubMed Central

    Robertson, J. S.; Dunstan, P. J.

    1972-01-01

    1. The metabolism of 1-oxo-octahydro- and 2- and 9-oxoperhydro-anthracenes was investigated in rabbits. All compounds increased the urinary glucuronide content. 2. The 1-oxo and 2-oxo compounds were reduced to the corresponding alcohols whereas the 9-oxo compound was hydroxylated. 3. The reduction in vitro of these compounds and related ketones was investigated with three different enzyme systems (liver alcohol dehydrogenase, hydroxy steroid dehydrogenase, aromatic aldehyde–ketone reductase) in an attempt to explain the results in vivo. 4. Successful reduction of many ketones with aromatic aldehyde–ketone reductase suggests that the kidney may be of importance in the reduction in vivo of certain cyclic carbonyl compounds. PMID:5073736

  18. Detection of inflammatory lymph nodes in rabbits by 99mTc-HIG lymphoscintigraphy.

    PubMed

    Ergün, E L; Bozkurt, M F; Ercan, M T; Ruacan, S; Sener, B; Unsal, I S

    2002-12-01

    Tc-Human immunoglobulin G ( Tc-HIG) is a well-known radiopharmaceutical for the evaluation of inflammatory lesions. Recently, it has been demonstrated as a new agent for the visualization of the lymphatic system by our group. Our aim was to investigate the feasibility of detection of inflammatory lymph nodes by Tc-HIG lymphoscintigraphy. Ten adult New Zealand rabbits were used as group A. In a baseline study, 37 MBq Tc-HIG (0.1 ml) was injected into both hind legs of the rabbits, and sequential posterior gamma imaging with the rabbits lying prone was performed at 5, 15, 30, 60, 90 and 120 min using a single-headed gamma camera (Toshiba GCA G01 E). One week later, microorganisms ( ) were injected in a volume of 0.1 ml intradermally into the web space between the second and third toes in the bilateral hind legs of each rabbit in order to obtain inflammation in the popliteal lymph nodes. After 4 days, 37 MBq Tc-HIG (0.1 ml) was injected into the hind legs of the rabbits bilaterally, and sequential posterior gamma imaging was performed as described above (second study). Another group of 10 adult New Zealand rabbits (group B) was injected with the same microorganisms in the right hind legs only. After 4 days, scintigraphic imaging was carried out in the same way as described above (third study). Regions of interest were drawn over the injection sites and popliteal lymph nodes on each image for semiquantitative analysis. Count rates for each were calculated and a decay correction was applied. Time-activity curves were generated to show the percentage retention of radioactivity in each region. After the scintigraphic study, some of the group B rabbits were killed by intravenous injection of pentobarbitone (100-150 mg.kg, and both left and right lymph nodes were removed for microscopic examination. On the scintigrams, lymphatic channels and popliteal lymph nodes were visualized within 15 min. In the second study, bilateral popliteal lymph nodes were visualized more clearly

  19. Posterior Vitreous Detachment With Microplasmin Alters the Retinal Penetration of Intravitreal Bevacizumab (Avastin) in Rabbit Eyes

    PubMed Central

    Goldenberg, David T.; Giblin, Frank J.; Cheng, Mei; Chintala, Shravan K.; Trese, Michael T.; Drenser, Kimberly A.; Ruby, Alan J.

    2010-01-01

    . At three days, one rabbit showed increased antibody labeling in the retina of the non-MP-injected eye compared with the contralateral MP-injected eye, and two rabbits exhibited similar antibody labeling in both eyes. When compared with control eyes, light microscopy demonstrated normal retinal histologic findings in eyes injected only with microplasmin. Conclusions Increased BV retinal penetration is observed initially in eyes with a MP-induced PVD, and the mechanism is likely multifactorial. By three days, retinal penetration is similar in eyes with and without a PVD. Although it is difficult to directly extrapolate to humans, our study suggests a PVD may alter the retinal penetration of BV. PMID:21099453

  20. Subtyping of Cryptosporidium cuniculus and genotyping of Enterocytozoon bieneusi in rabbits in two farms in Heilongjiang Province, China

    PubMed Central

    Yang, Ziyin; Zhao, Wei; Shen, Yujuan; Zhang, Weizhe; Shi, Ying; Ren, Guangxu; Yang, Di; Ling, Hong; Yang, Fengkun; Liu, Aiqin; Cao, Jianping

    2016-01-01

    Cryptosporidium spp. and Enterocytozoon bieneusi are two prevalent opportunistic pathogens in humans and animals. Currently, few data are available on genetic characterization of both pathogens in rabbits in China. The aim of the present study was to understand prevalence and genetic characterization of Cryptosporidium spp. and E. bieneusi in rabbits. We collected 215 fecal samples from 150 Rex rabbits and 65 New Zealand White rabbits on two different farms in Heilongjiang Province, China. Cryptosporidium spp. and E. bieneusi were tested by polymerase chain reaction (PCR) and sequencing the partial small subunit of ribosomal DNA (SSU rDNA) and the internal transcribed spacer (ITS) region of rDNA, respectively. Cryptosporidium was detected in 3.3% (5/150) of Rex rabbits and 29.2% (19/65) of New Zealand White rabbits. All the 24 Cryptosporidium isolates were identified as C. cuniculus. Enterocytozoon bieneusi was only found in 14.7% (22/150) of Rex rabbits. Five known genotypes: CHN-RD1 (n = 12), D (n = 3), Type IV (n = 2), Peru6 (n = 1), and I (n = 1), and three novel ones CHN-RR1 to CHN-RR3 (one each) were detected. By analyzing the 60-kDa glycoprotein (gp60) gene sequences of C. cuniculus isolates, three subtypes were obtained: VbA28 (n = 2), VbA29 (n = 16), and VbA32 (n = 3). All these three C. cuniculus subtypes were reported previously in humans. Four known E. bieneusi genotypes have been found to be present in humans. The three novel ones fell into zoonotic group 1. The results suggest zoonotic potential of C. cuniculus and E. bieneusi isolates in rabbits. PMID:27882867

  1. Heavy metals in meat of Finnish city rabbits.

    PubMed

    Damerau, A; Venäläinen, E R; Peltonen, K

    2012-01-01

    Levels of cadmium, chromium, lead, copper, manganese and zinc in city rabbits were determined to evaluate the edibility of the meat. Mean concentrations of toxic metals were 0.011 mg/kg for cadmium and 0.037 mg/kg for lead. Cadmium and lead concentrations were below the admissible maximum levels set by the EU. Concentrations of toxic metals in the meat were sufficiently low as to assume that consumption of the meat does not pose a health risk for human health. Investigation of polycyclic aromatic hydrocarbons, pesticides and other environmental pollutants is required before the meat can be declared to be completely safe.

  2. A novel approach for the annulus needle puncture model of intervertebral disc degeneration in rabbits

    PubMed Central

    Lei, Tao; Zhang, Yuan; Zhou, Qiang; Luo, Xiaoji; Tang, Ke; Chen, Rongsheng; Yu, Chang; Quan, Zhengxue

    2017-01-01

    Objective: To create the rabbit animal model of intervertebral disc (IVD) degeneration by the annulus needle puncture technique through a novel transabdominal approach. Methods: Thirteen New Zealand White rabbits underwent annular puncture at the L3/4, L4/5, and L5/6 discs through a transabdominal approach. For a longitudinal study to assess changes in disc height over time, serial X-rays, T2-weighted magnetic resonance imaging (MRI) (T2WI), and T2 mapping MRI were performed pre-operation and at 2, 4, and 6 weeks after puncture. Three rabbits were randomly selected for histological evaluation at 4 weeks post-operation. In addition, the remaining rabbits underwent a second surgery at 6 weeks after puncture. Results: All rabbits underwent the initial and second surgeries successfully without nerve-related complications. The operations had no significant effects on the rabbit body weight, and partial mild intra-abdominal adhesions were found in only 1 rabbit. The punctured discs were confirmed to be those of interest post-surgery and displayed progressive degeneration in disc height index (%), T2WI, and T2 relaxation time over time. At 4 weeks after puncture, a histological analysis revealed notochordal cell loss from the nucleus pulposus, fibrocartilage filling the nucleus pulposus space, and annulus fibrosus disorganization. Conclusion: The annular needle puncture model established through a transabdominal approach, which demonstrates better visualization, exact identification, consistent degeneration degrees and minimal complications, is radiologically and histologically consistent with human IVD degeneration. T2 mapping MRI can quantitatively discriminate between grades of mild degeneration. PMID:28386320

  3. In vivo effects of horse and rabbit antithymocyte globulin in patients with severe aplastic anemia.

    PubMed

    Feng, Xingmin; Scheinberg, Phillip; Biancotto, Angelique; Rios, Olga; Donaldson, Sarah; Wu, Colin; Zheng, Haiyun; Sato, Kazuya; Townsley, Danielle M; McCoy, J Philip; Young, Neal S

    2014-09-01

    We recently reported that rabbit antithymocyte globulin was markedly inferior to horse antithymocyte globulin as a primary treatment for severe aplastic anemia. Here we expand on our findings in this unique cohort of patients. Rabbit antithymocyte globulin was detectable in plasma for longer periods than horse antithymocyte globulin; rabbit antithymocyte globulin in plasma retained functional capacity to bind to lymphocytes for up to 1 month, horse antithymocyte globulin for only about 2 weeks. In the first week after treatment there were much lower numbers of neutrophils in patients treated with rabbit antithymocyte globulin than in patients receiving horse antithymocyte globulin. Both antithymocyte globulins induced a "cytokine storm" in the first 2 days after administration. Compared with horse antithymocyte globulin, rabbit antithymocyte globulin was associated with higher levels of chemokine (C-C motif) ligand 4 during the first 3 weeks. Besides a much lower absolute number and a lower relative frequency of CD4(+) T cells, rabbit antithymocyte globulin induced higher frequencies of CD4(+)CD38(+), CD3(+)CD4(-)CD8(-) T cells, and B cells than did horse antithymocyte globulin. Serum sickness occurred around 2 weeks after infusion of both types of antithymocyte globulin. Human anti-antithymocyte globulin antibodies, especially of the IgM subtype, correlated with serum sickness, which appeared concurrently with clearance of antithymocyte globulin in blood and with the production of cytokines. In conclusion, rabbit and horse antithymocyte globulins have very different pharmacokinetics and effects on neutrophils, lymphocyte subsets, and cytokine release. These differences may be related to their efficacy in suppressing the immune system and restoring hematopoiesis in bone marrow failure. Clinicaltrials.gov identifier: NCT00260689.

  4. Rabbit colony infected with a bovine-like G6P[11] rotavirus strain.

    PubMed

    Schoondermark-van de Ven, Esther; Van Ranst, Marc; de Bruin, Wieke; van den Hurk, Patrick; Zeller, Mark; Matthijnssens, Jelle; Heylen, Elisabeth

    2013-09-27

    Group A rotaviruses (RVAs) are the main etiological agent of infantile diarrhea in both humans and animals worldwide. A limited number of studies have investigated the molecular characteristics of RVA strains in stool specimens of rabbits, with only a few lapine RVA strains isolated and (partially) characterized to date. The most common G/P-genotype combinations found in rabbits are G3P[14] and G3P[22]. In this study a RVA strain was isolated from the small intestine of a 9-week-old rabbit from an infected laboratory rabbit colony. The RVA strain RVA/Rabbit-tc/NLD/K1130027/2011/G6P[11] was shown to possess the typical bovine G6 and P[11] genotypes. The complete genome of this unusual lapine strain was sequenced and characterized. Phylogenetic analyses of all 11 gene segments revealed the following genotype constellation: G6-P[11]-I2-R2-C2-M2-A13-N2-T6-E2-H3. The VP1, VP2, VP3, VP6, NSP2 and NSP4 genes all belonged to DS-1-like genotype 2, but clustered more closely to bovine RVA strains than to lapine RVA strains. The NSP1 genotype A13 is typically associated with bovine RVAs, while the NSP3 genotype T6 and the NSP5 genotype H3 have been found in a wide variety of species. However, the isolated strain clustered within bovine(-like) T6 and H3 subclusters. Overall, the data indicate that the RVA strain is most closely related to bovine-like RVA strains and most likely represents a direct interspecies transmission from a cow to a rabbit. Altogether, these findings indicate that a RVA strain with an entirely bovine genome constellation was able to infect and spread in a laboratory rabbit colony.

  5. 9 CFR 3.61 - Primary enclosures used to transport live rabbits.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Primary enclosures used to transport live rabbits. 3.61 Section 3.61 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE ANIMAL WELFARE STANDARDS Specifications for the Humane Handling, Care,...

  6. Rabbit haemorrhagic disease: field epidemiology and the management of wild rabbit populations.

    PubMed

    Cooke, B D

    2002-08-01

    Rabbit haemorrhagic disease (RHD) has become established in wild rabbit populations throughout Western Europe, Australia and New Zealand. The abundance of wild rabbits has been significantly reduced, particularly in drier areas of southern Spain, inland Australia and South Island New Zealand. A detailed knowledge of the epidemiology of RHD is essential for the management of the disease in natural rabbit populations, either to rebuild or to control populations. When RHD first spread among naive wild rabbits, epidemiological studies provided unique information on the rate of spread, the possible role of insect vectors in transmission, and the correlation between the impact of disease on populations and climatic variables. Current research shows a consistent pattern of epidemiology between Europe and Australasia. Typically, the most severe epizootics of RHD occur among young sub-adult rabbits which have lost age-related resilience and maternal antibodies. However, the timing of these outbreaks reflects climatic variables that determine the breeding season of the rabbits and the periods when RHD virus (RDHV) is most likely to persist and spread. Further factors that may complicate epidemiology include the possibility that non-pathogenic RHDV-like viruses are present in natural rabbit populations. Additionally, the question of how the virus persists from year to year remains unresolved; persistence in carrier rabbits is a possibility. Understanding of the epidemiology of RHD is now sufficiently advanced to consider the possibility of manipulating rabbit populations to alter the epidemiological pattern of RHD and thereby maximise or minimise the mortality caused by the disease. Altering the epidemiology of RHD in this manner would assist the management of wild rabbit populations either for conservation or pest control purposes.

  7. Myxoma virus M156 is a specific inhibitor of rabbit PKR but contains a loss-of-function mutation in Australian virus isolates

    PubMed Central

    Peng, Chen; Haller, Sherry L.; Rahman, Masmudur M.; McFadden, Grant; Rothenburg, Stefan

    2016-01-01

    Myxoma virus (MYXV) is a rabbit-specific poxvirus, which is highly virulent in European rabbits. The attenuation of MYXV and the increased resistance of rabbits following the release of MYXV in Australia is one of the best-documented examples of host–pathogen coevolution. To elucidate the molecular mechanisms that contribute to the restriction of MYXV infection to rabbits and MYXV attenuation in the field, we have studied the interaction of the MYXV protein M156 with the host antiviral protein kinase R (PKR). In yeast and cell-culture transfection assays, M156 only inhibited rabbit PKR but not PKR from other tested mammalian species. Infection assays with human HeLa PKR knock-down cells, which were stably transfected with human or rabbit PKR, revealed that only human but not rabbit PKR was able to restrict MYXV infection, whereas both PKRs were able to restrict replication of a vaccinia virus (VACV) strain that lacks the PKR inhibitors E3 and K3. Inactivation of M156R led to MYXV virus attenuation in rabbit cells, which was rescued by the ectopic expression of VACV E3 and K3. We further show that a mutation in the M156 encoding gene that was identified in more than 50% of MYXV field isolates from Australia resulted in an M156 variant that lost its ability to inhibit rabbit PKR and led to virus attenuation. The species-specific inhibition of rabbit PKR by M156 and the M156 loss-of-function in Australian MYXV field isolates might thus contribute to the species specificity of MYXV and to the attenuation in the field, respectively. PMID:26903626

  8. Myxoma virus M156 is a specific inhibitor of rabbit PKR but contains a loss-of-function mutation in Australian virus isolates.

    PubMed

    Peng, Chen; Haller, Sherry L; Rahman, Masmudur M; McFadden, Grant; Rothenburg, Stefan

    2016-04-05

    Myxoma virus (MYXV) is a rabbit-specific poxvirus, which is highly virulent in European rabbits. The attenuation of MYXV and the increased resistance of rabbits following the release of MYXV in Australia is one of the best-documented examples of host-pathogen coevolution. To elucidate the molecular mechanisms that contribute to the restriction of MYXV infection to rabbits and MYXV attenuation in the field, we have studied the interaction of the MYXV protein M156 with the host antiviral protein kinase R (PKR). In yeast and cell-culture transfection assays, M156 only inhibited rabbit PKR but not PKR from other tested mammalian species. Infection assays with human HeLa PKR knock-down cells, which were stably transfected with human or rabbit PKR, revealed that only human but not rabbit PKR was able to restrict MYXV infection, whereas both PKRs were able to restrict replication of a vaccinia virus (VACV) strain that lacks the PKR inhibitors E3 and K3. Inactivation of M156R led to MYXV virus attenuation in rabbit cells, which was rescued by the ectopic expression of VACV E3 and K3. We further show that a mutation in the M156 encoding gene that was identified in more than 50% of MYXV field isolates from Australia resulted in an M156 variant that lost its ability to inhibit rabbit PKR and led to virus attenuation. The species-specific inhibition of rabbit PKR by M156 and the M156 loss-of-function in Australian MYXV field isolates might thus contribute to the species specificity of MYXV and to the attenuation in the field, respectively.

  9. Immunotherapy for Alzheimer's disease: harnessing our knowledge of T cell biology using a cholesterol-fed rabbit model.

    PubMed

    Coico, Richard; Woodruff-Pak, Diana S

    2008-12-01

    This timely special issue of the Journal of Alzheimer's Disease provides the opportunity to examine interfaces between basic science and clinical medicine using animal models to develop more effective therapies for the treatment and, ideally, prevention of Alzheimer's disease (AD). That some patients with AD enrolled in a clinical trial to inoculate against amyloid-beta (Abeta) experienced a misdirected polarization of Th cells reminds us that our knowledge of T cell biology, immune regulation, and the precise functional properties of adjuvants is incomplete. We review this knowledge and consider the advantages of the rabbit for immunological studies. The langomorph species is proximate to primates on the phylogenetic scale, its amino acid sequence of Abeta is 97% identical to the human Abeta sequence, and the rabbit model system is extensively characterized on a form of associative learning with parallels in normal aging in rabbits and humans that is severely impaired in human AD. Cholesterol-fed rabbits treated with Abeta immunotherapy generate high titer anti-Abeta responses. The cholesterol-fed rabbit model of AD with its close parallels to human genetics and physiology, along with its validity from molecular to cognitive levels as a model of human AD, provides a promising vehicle for development of immunotherapies.

  10. Intrastromal Injection of China Painting Ink in Corneas of Male Rabbits: Clinical and Histological Study

    PubMed Central

    Alsmman Hassan, Alahmady Hamad; Abd Elhaliem Soliman, Nesreen Gamal-Eldeen

    2016-01-01

    Background. Many patients with corneal opacity or complicated cataract in blind eye ask for cosmoses. In this study we tried to investigate the staining of corneas of male rabbits by Rotring China painting ink and to study the histological changes. Method. 10 eyes of 10 male Baladi Egyptian rabbits were injected (0.1 mL) intrastromally in the cornea by the use of China painting ink (Rotring Tinta China) through insulin syringe (27-gauge needle) by single injection; clinical follow-up is for 6 months and lastly the rabbits were scarified and the stained eyes were enucleated for histological analysis. Results. Clinically the stain was stable in color and distribution in corneas with no major complications. Histological results of the stained rabbit corneas showed blackish pigmentation in the corneal stroma without any inflammatory cellular infiltration. Some fibroblast cells had pigment granules in their cytoplasm in the adjacent layers. Conclusion. Corneal staining by China painting ink is effective and safe in staining of male rabbits cornea; however further study in human corneas with longer follow-up period is advisable. PMID:27195146

  11. Experiment studies of iodinated oil nanometer ferrofluid retention in rabbit liver.

    PubMed

    Zhang, X; Lin, R; Lin, Y; Wu, R H

    2005-01-01

    To study possibility for iodinated oil nanometer ferrofluid retention in rabbit liver. 131I- iodinated oil nanometer ferrofluid were injected into liver right lobe through portal vein in 5 rabbits... - calibrate meter showed continuous.. counts in the region injected. Then the relative metabolic parameters were calculated. Left lobe livers, right lobe livers and lungs of the rabbits were examined in pathology, and the right lobe livers were examined by electron microscope. Five rabbits injected purely 131Iiodinated oil were designated as control group. Single metabolic mode was found in the rabbits in nanometer ferrofluid group. The biological half-life of 131I- iodinated oil nanometer ferrofluid was not different from control group's slow metabolic portion. But control group's rapid metabolic portion were eliminated in a higher speed, range from 8% to 44%. More damage was found in nanometer ferrofluid group's right lobe livers. 131I- iodinated oil nanometer ferrofluid possess the opportunity of local retention in human body and further study is worthwhile.

  12. Paradoxical increase in the bispectral index during deep anesthesia in New Zealand white rabbits.

    PubMed

    Romanov, Alexander; Moon, Rajinder-Singh; Wang, Mei; Joshi, Shailendra

    2014-01-01

    Objective monitoring of the level of anesthesia is crucial in carefully controlled translational neuroscience studies. The usefulness of bispectral index (BIS) in monitoring human anesthesia is well established. However, the validity of its application remains unproven in laboratory animals. We assessed whether BIS could be used reliably in monitoring the depth of deep anesthesia in 8 New Zealand white rabbits. Experimental baseline anesthesia was maintained with continuous infusion of propofol and administration of isoflurane, both of which were titrated to EEG activity. The rabbits were allocated randomly to receive 3 increasing concentrations of common anesthetic drugs (etomidate, propofol, and isoflurane) aimed to produce burst suppression of EEG activity yielding at least 10 s of sustained EEG silence. Rabbits had a 20-min recovery interval between challenges. Transient cerebral hypoperfusion to produce reversible EEG silence due to ischemia was induced as a fourth challenge, followed by terminal arrest, in each animal. BIS, EEG, and physiologic data were analyzed for each rabbit. We observed stable BIS values in the range of 40 to 60 during the administration of baseline anesthesia. However, as the depth of anesthesia deepened with the anesthetic drug challenges, the BIS value paradoxically increased with increasing doses. The BIS signal quality index declined while the total power decreased. In contrast to these unexpected results, BIS values decreased rapidly to near 0 during terminal arrest, as expected. Therefore, we do not consider BIS to be a useful method for monitoring deep levels of anesthesia in laboratory rabbits.

  13. Tetomilast attenuates elastase-induced pulmonary emphysema through inhibition of oxidative stress in rabbits.

    PubMed

    Baila, Bulin; Ohno, Yasushi; Nagamoto, Hisashi; Kotosai, Kounori; Yabuuchi, Youichi; Funaguchi, Norihiko; Ito, Fumitaka; Endo, Junki; Mori, Hidenori; Takemura, Genzou; Fujiwara, Takako; Fujiwara, Hisayoshi; Minatoguchi, Shinya

    2012-01-01

    Tetomilast was originally identified as a potent inhibitor of superoxide production in human neutrophils, and is of interest because it may relieve oxidative stress related to chronic obstructive pulmonary disease (COPD). Our objective was to determine whether tetomilast effectively protects against the development of porcine pancreatic elastase (PPE)-induced emphysema in rabbits. Rabbits were divided into three groups (sham n=19, PPE n=19, PPE/Tetomilast n=18). The rabbits were once daily orally administered vehicle solution or tetomilast 5 d/week for 4 weeks before the PPE instillation. We compared pulmonary function, inflammatory cell infiltration, oxidative stress, and the incidences of apoptosis among the three groups. Tetomilast suppressed PPE-induced increases in the incidence of apoptosis and the production of 8-hydroxy-deoxyguanosine (8-OHdG) in lung tissues. PPE-instilled rabbits treated with tetomilast showed significantly less mean linear intercept and significantly better pulmonary function than rabbits administered PPE alone. Tetomilast may inhibit the development of emphysema by attenuating pulmonary inflammation and apoptosis caused by PPE-induced oxidative stress.

  14. Dermal irritation of petrolatum in rabbits but not in mice, rats or minipigs.

    PubMed

    Chandra, S A; Peterson, R A; Melich, D; Merrill, C M; Bailey, D; Mellon-Kusibab, K; Adler, R

    2014-08-01

    Petrolatum is widely used in cosmetics, topical pharmaceuticals and also as a vehicle in dermal toxicity studies. New Zealand white rabbits treated with white petrolatum (vehicle control) in a 2-week dermal irritation study exhibited moderate to severe erythema starting on Day 7 that subsided towards the end of the study. Histological examination of abraded and non-abraded petrolatum-treated skin obtained at termination (Day 15) revealed mild acanthosis, hyperkeratosis, dermal edema with mixed inflammatory cells in the dermis. Macroscopic and microscopic features noted in rabbits were consistent with dermal irritation to petrolatum. Wistar-Han rats, CD1 mice, C57/Bl/6J mice and Göttingen minipigs treated topically with white petrolatum did not exhibit clinical or histologic evidence of dermal irritation. Therapeutic agents developed for topical application are generally tested in rabbits during some point in development. Interpretation of skin irritation data from a single species can impact risk assessment for humans and on product labeling.

  15. Insights into Campylobacter jejuni colonization and enteritis using a novel infant rabbit model

    PubMed Central

    Shang, Yuwei; Ren, Fangzhe; Song, Zhaojun; Li, Qiuchun; Zhou, Xiaohui; Wang, Xiaobo; Xu, Zhonglan; Bao, Guangyu; Wan, Ting; Lei, Tianyao; Wang, Nan; Jiao, Xin-an; Huang, Jinlin

    2016-01-01

    A lack of relevant disease models for Campylobacter jejuni has long been an obstacle to research into this common enteric pathogen. Here we used an infant rabbit to study C. jejuni infection, which enables us to define several previously unknown but key features of the organism. C. jejuni is capable of systemic invasion in the rabbit, and developed a diarrhea symptom that mimicked that observed in many human campylobacteriosis. The large intestine was the most consistently colonized site and produced intestinal inflammation, where specific cytokines were induced. Genes preferentially expressed during C. jejuni infection were screened, and acs, cj1385, cj0259 seem to be responsible for C. jejuni invasion. Our results demonstrates that the infant rabbit can be used as an alternative experimental model for the study of diarrheagenic Campylobacter species and will be useful in exploring the pathogenesis of other related pathogens. PMID:27357336

  16. Negative cross-reactivity of rabbit anti-Malassezia furfur antibodies with other yeasts.

    PubMed

    Chua, Kaw Bing; Devi, Shamala; Ng, Kee Peng; Hooi, Poh Sim; Na, Shiang Ling; Chua, Kerk Hsiang

    2005-12-01

    Anti-Malassezia furfur monospecific polyclonal antibodies was produced by repeated immunization of rabbit with Malassezia furfur yeast cells mixed with Freud adjuvant. The antibody titres of respective rabbit's serum samples prior to and after each immunization against M. furfur were assayed by indirect immunofluorescence technique using the M. furfur whole yeast antigen fixed in Teflon coated slides. The highest anti-M. furfur antibody titre achieved was 1 in 1280 dilution. At 1:20 dilution, none of the respective serum samples taken at various stages of immunization gave positive immunofluorescent staining against any of the other species of yeasts tested in this study. Anti-M. furfur monospecific polyclonal antibodies produced in rabbit in this study has the potential for diagnostic application in immunohistochemical detection of M. furfur in human tissues.

  17. Ultrastructural and pharmacologic studies on laser-induced glaucoma in primates and rabbits

    SciTech Connect

    March, W.F.; Gherezghiher, T.; Koss, M.; Nordquist, R.

    1984-01-01

    Sustained high intraocular pressure resulting in optic nerve cupping and loss of ganglion cells was produced in five rhesus monkeys and eight pigmented rabbits by applying argon laser energy to the trabecular meshwork. In addition, the rabbits manifested buphthalmus. Flow of carbon particles subsequently injected into the anterior chamber was obstructed at the trabecular meshwork by a wound-healing response that closed the intratrabecular spaces. Besides this sustained high intraocular pressure as a result of late scarring, an acute hypertensive response was seen in all rabbits which may correspond to the acute hypertension seen after laser trabeculoplasty in humans. The acute hypertensive response could be only partially blocked by prostaglandin inhibitors and the authors believe that prostaglandins are not primarily responsible for this effect. Medications known to lower intraocular pressure were systematically tested in both glaucoma models.

  18. Embryo-Fetal Developmental Toxicity Studies with Pregabalin in Mice and Rabbits.

    PubMed

    Morse, Dennis C

    2016-04-01

    Pregabalin was evaluated for potential developmental toxicity in mice and rabbits. Pregabalin was administered once daily by oral gavage to female albino mice (500, 1250, or 2500 mg/kg) and New Zealand White rabbits (250, 500, or 1250 mg/kg) during organogenesis (gestation day 6 through 15 [mice] or 6 through 20 [rabbits]). Fetuses were evaluated for viability, growth, and morphological development. Pregabalin administration to mice did not induce maternal or developmental toxicity at doses up to 2500 mg/kg, which was associated with a maternal plasma exposure (AUC0-24 ) of 3790 μg•hr/ml, ≥30 times the expected human exposure at the maximum recommended daily dose (MRD; 600 mg/day). In rabbits, treatment-related clinical signs occurred at all doses (AUC0-24 of 1397, 2023, and 4803 μg•hr/ml at 250, 500, and 1250 mg/kg, respectively). Maternal toxicity was evident at all doses and included ataxia, hypoactivity, and cool to touch. In addition, abortion and females euthanized moribund with total resorption occurred at 1250 mg/kg. There were no treatment-related malformations at any dose. At 1250 mg/kg, compared with study and historical controls, the percentage of fetuses with retarded ossification was significantly increased and the mean number of ossification sites was decreased, which correlated with decreased fetal and placental weights, consistent with in utero growth retardation. Therefore, the no-effect dose for developmental toxicity in rabbits was 500 mg/kg, which produced systemic exposure approximately 16-times human exposure at the MRD. These findings indicate that pregabalin, at the highest dose tested, was not teratogenic in mice or rabbits.

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

    PubMed Central

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

    1965-01-01

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

  20. Gene Expression Profiling of Pulmonary Artery in a Rabbit Model of Pulmonary Thromboembolism

    PubMed Central

    Huang, Jianfei; Zhou, Xiaoyu; Xie, Hao; Zhu, Qilin; Huang, Minjie

    2016-01-01

    Acute pulmonary thromboembolism (PTE) refers to the obstruction of thrombus in pulmonary artery or its branches. Recent studies have suggested that PTE-induced endothelium injury is the major physiological consequence of PTE. And it is reasonal to use PTE-induced endothelium injury to stratify disease severity. According to the massive morphologic and histologic findings, rabbit models could be applied to closely mimic the human PE. Genomewide gene expression profiling has not been attempted in PTE. In this study, we determined the accuracy of rabbit autologous thrombus PTE model for human PTE disease, then we applied gene expression array to identify gene expression changes in pulmonary arteries under PTE to identify potential molecular biomarkers and signaling pathways for PTE. We detected 1343 genes were upregulated and 923 genes were downregulated in PTE rabbits. The expression of several genes (IL-8, TNF-α, and CXCL5) with functional importance were further confirmed in transcript and protein levels. The most significantly differentially regulated genes were related to inflammation, immune disease, pulmonary disease, and cardiovascular diseases. Totally 87 genes were up-regulated in the inflammatory genes. We conclude that gene expression profiling in rabbit PTE model could extend the understanding of PTE pathogenesis at the molecular level. Our study provides the fundamental framework for future clinical research on human PTE, including identification of potential biomarkers for prognosis or therapeutic targets for PTE. PMID:27798647

  1. Gene Expression Profiling of Pulmonary Artery in a Rabbit Model of Pulmonary Thromboembolism.

    PubMed

    Tang, Zhiyuan; Wang, Xudong; Huang, Jianfei; Zhou, Xiaoyu; Xie, Hao; Zhu, Qilin; Huang, Minjie; Ni, Songshi

    2016-01-01

    Acute pulmonary thromboembolism (PTE) refers to the obstruction of thrombus in pulmonary artery or its branches. Recent studies have suggested that PTE-induced endothelium injury is the major physiological consequence of PTE. And it is reasonal to use PTE-induced endothelium injury to stratify disease severity. According to the massive morphologic and histologic findings, rabbit models could be applied to closely mimic the human PE. Genomewide gene expression profiling has not been attempted in PTE. In this study, we determined the accuracy of rabbit autologous thrombus PTE model for human PTE disease, then we applied gene expression array to identify gene expression changes in pulmonary arteries under PTE to identify potential molecular biomarkers and signaling pathways for PTE. We detected 1343 genes were upregulated and 923 genes were downregulated in PTE rabbits. The expression of several genes (IL-8, TNF-α, and CXCL5) with functional importance were further confirmed in transcript and protein levels. The most significantly differentially regulated genes were related to inflammation, immune disease, pulmonary disease, and cardiovascular diseases. Totally 87 genes were up-regulated in the inflammatory genes. We conclude that gene expression profiling in rabbit PTE model could extend the understanding of PTE pathogenesis at the molecular level. Our study provides the fundamental framework for future clinical research on human PTE, including identification of potential biomarkers for prognosis or therapeutic targets for PTE.

  2. Experimental Toxoplasmic Lymphadenopathy in Rabbits

    PubMed Central

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

    1973-01-01

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

  3. Evaluation of electrosurgical meniscectomy in rabbits.

    PubMed

    Schosheim, P M; Caspari, R B

    1986-01-01

    Recently, electrosurgical cutting instruments utilizing radiofrequency energy have been designed as arthroscopic devices for cutting meniscal tissue. This study attempted to determine the in vivo gross and microscopic effects of radiofrequency energy on meniscal tissue in rabbits. Twelve adult New Zealand white rabbits (48 menisci) underwent bilateral knee arthrotomies. Ten rabbits (40 menisci) underwent partial meniscectomies in which one half of each meniscus in the longitudinal plane was removed with the electrosurgical generator. Two control rabbits underwent arthrotomy without resection of meniscal tissue. At specific time intervals, the rabbits were killed, and the menisci were removed. The gross specimens were photographed, and microscopic sections of each meniscus were fixed and stained. Specimens were evaluated to determine the cellular and vascular response to the electrosurgical cut edge of each meniscus. The microscopic specimens revealed that the radiofrequency cutting instruments produced a small degree of direct thermal damage to the cut meniscus. A tissue response producing a hypercellular dense collagen matrix was present for approximately 3 months. The spontaneous repair of tissue was complete by 6 months, and the histologic 6-month specimens could not be distinguished from the 6-month control specimens except with respect to the overall width of the specimens.

  4. Hypercholesterolemia Impaired Sperm Functionality in Rabbits

    PubMed Central

    Monclus, Maria A.; Cabrillana, Maria E.; Clementi, Marisa A.; Espínola, Leandro S.; Cid Barría, Jose L.; Vincenti, Amanda E.; Santi, Analia G.; Fornés, Miguel W.

    2010-01-01

    Hypercholesterolemia represents a high risk factor for frequent diseases and it has also been associated with poor semen quality that may lead to male infertility. The aim of this study was to analyze semen and sperm function in diet-induced hypercholesterolemic rabbits. Twelve adult White New Zealand male rabbits were fed ad libitum a control diet or a diet supplemented with 0.05% cholesterol. Rabbits under cholesterol-enriched diet significantly increased total cholesterol level in the serum. Semen examination revealed a significant reduction in semen volume and sperm motility in hypercholesterolemic rabbits (HCR). Sperm cell morphology was seriously affected, displaying primarily a “folded head”-head fold along the major axe-, and the presence of cytoplasmic droplet on sperm flagellum. Cholesterol was particularly increased in acrosomal region when detected by filipin probe. The rise in cholesterol concentration in sperm cells was determined quantitatively by Gas chromatographic-mass spectrometric analyses. We also found a reduction of protein tyrosine phosphorylation in sperm incubated under capacitating conditions from HCR. Interestingly, the addition of Protein Kinase A pathway activators -dibutyryl-cyclic AMP and iso-butylmethylxanthine- to the medium restored sperm capacitation. Finally, it was also reported a significant decrease in the percentage of reacted sperm in the presence of progesterone. In conclusion, our data showed that diet-induced hypercholesterolemia adversely affects semen quality and sperm motility, capacitation and acrosomal reaction in rabbits; probably due to an increase in cellular cholesterol content that alters membrane related events. PMID:20976152

  5. 9 CFR 354.124 - Quarantine of diseased rabbits.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... shall be dealt with in one of the following ways: (a) If it is determined by a veterinary inspector that... veterinary inspector that further handling of the rabbits will not create a health hazard, such rabbits...

  6. Physiological and biochemical changes after boldenone injection in adult rabbits.

    PubMed

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

    2016-01-01

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

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

    PubMed

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

    2014-01-01

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

  8. 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

  9. Management of hepatitis E virus (HEV) zoonotic transmission: protection of rabbits against HEV challenge following immunization with HEV 239 vaccine.

    PubMed

    Liu, Peng; Du, Ren jie; Wang, Ling; Han, Jian; Liu, Lin; Zhang, Yu lin; Xia, Jun ke; Lu, Feng min; Zhuang, Hui

    2014-01-01

    Hepatitis E virus (HEV) constitutes a significant health burden worldwide, with an estimated approximately 33% of the world's population exposed to the pathogen. The recent licensed HEV 239 vaccine in China showed excellent protective efficacy against HEV of genotypes 1 and 4 in the general population and pregnant women. Because hepatitis E is a zoonosis, it is also necessary to ascertain whether this vaccine can serve to manage animal sources of human HEV infection. To test the efficacy of the HEV 239 vaccine in protecting animal reservoirs of HEV against HEV infection, twelve specific-pathogen-free (SPF) rabbits were divided randomly into two groups of 6 animals and inoculated intramuscularly with HEV 239 and placebo (PBS). All animals were challenged intravenously with swine HEV of genotype 4 or rabbit HEV seven weeks after the initial immunization. The course of infection was monitored for 10 weeks by serum ALT levels, duration of viremia and fecal virus excretion and HEV antibody responses. All rabbits immunized with HEV 239 developed high titers of anti-HEV and no signs of HEV infection were observed throughout the experiment, while rabbits inoculated with PBS developed viral hepatitis following challenge, with liver enzyme elevations, viremia, and fecal virus shedding. Our data indicated that the HEV 239 vaccine is highly immunogenic for rabbits and that it can completely protect rabbits against homologous and heterologous HEV infections. These findings could facilitate the prevention of food-borne sporadic HEV infection in both developing and industrialized countries.

  10. 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

  11. Complement (C5)-derived chemotactic activity accounts for accumulation of polymorphonuclear leukocytes in cerebrospinal fluid of rabbits with pneumococcal meningitis.

    PubMed Central

    Ernst, J D; Hartiala, K T; Goldstein, I M; Sande, M A

    1984-01-01

    Experiments were performed to identify the chemoattractant for polymorphonuclear leukocytes that appears in the cerebrospinal fluid of rabbits with experimental pneumococcal meningitis. Meningitis was induced in anesthetized New Zealand white rabbits by injecting 10(4) cells of stationary-phase Streptococcus pneumoniae type III intracisternally. Before bacteria were injected, cerebrospinal fluid contained neither polymorphonuclear leukocytes nor chemotactic activity. Significant chemotactic activity for rabbit polymorphonuclear leukocytes was detected 12 h after inoculation with bacteria and was maximal after 18 to 20 h. Chemotactic activity appeared in cerebrospinal fluid while concentrations of pneumococci and total protein were increasing but before there was any accumulation of polymorphonuclear leukocytes. The chemotactic activity in cerebrospinal fluid was heat stable (56 degrees C for 30 min), eluted from Sephadex G-75 with a profile identical to that of the chemotactic activity in zymosan-activated rabbit serum, and was inhibited by treatment with antibodies to native human C5. In addition, preincubation of polymorphonuclear leukocytes with partially purified rabbit C5a selectively inhibited their subsequent chemotactic responses to cerebrospinal fluid. These data indicate that complement (C5)-derived chemotactic activity appears in cerebrospinal fluid during the course of experimental pneumococcal meningitis in rabbits and suggest that this activity accounts for the accumulation of polymorphonuclear leukocytes observed in this infection. PMID:6480117

  12. Serological Survey for RHD Antibodies in Rabbits from Two Types of Rabbit Breeding Farms.

    PubMed

    Fitzner, A; Niedbalski, W

    2016-09-01

    Seroprevalence studies of RHDV antibodies in domestic rabbits were conducted between 2008-2014. A total of 12,169 sera from the provinces of central, southern and south-east Poland, including 7,570 samples collected from mixed-breed rabbits reared in smallholder farms and nearly 4,600 sera taken mainly from unvaccinated rabbits kept in industrial farms, were examined using ELISA tests. Additionally, cross-reactivity of selected tested and control archival sera using both classic RHDV and RHDVa antigens was determined by HI assay. The overall seroprevalence was 13.3%. In rabbits with unkown history of immunisation or RHD infection which came from small farms, RHDV antibodies were detected in 6.1% ranging between 1.0% to 17.2% of animals. In rabbits of the same group, but with a declared vaccination status, or confirmed exposure to an infectious virus, or coming from exposed females, the seroprevalence ranged from 83% to 100%. Among unvaccinated meat rabbits aged 71 to 90 days from industrial farms, low (1.85%, 4.17%, 11%), medium (34%, 54%) or high rates (98.7%) of seropositivity were detected. The seroconversion recorded in adult vaccinated females from industrial farms was 70% and 95%. Generally, the antibody levels examined by ELISAs and HI were comparable. However, a number of sera from the rabbits from small farms, as well as archival sera, showed clear differences. Several-fold differences in antibody titers, evidenced mainly in the postoutbreak sera, indictaed the contact of animals with RHDVa antigen. The overall results of the survey revealed a great proportion of seronegative rabbits potentially highly susceptible to RHD infection. In combination with the emergence of a novel pathogenic RHD virus type (RHDV2), it poses a severe risk of a next wave of fatal disease cases spreading in the native population of domestic rabbits, especially in farms with a traditional system of husbandry.

  13. Comparing rat and rabbit embryo-fetal developmental toxicity data for 379 pharmaceuticals: on systemic dose and developmental effects.

    PubMed

    Theunissen, Peter T; Beken, Sonia; Beyer, Bruce; Breslin, William J; Cappon, Gregg D; Chen, Connie L; Chmielewski, Gary; de Schaepdrijver, Luc; Enright, Brian; Foreman, Jennifer E; Harrouk, Wafa; Hew, Kok-Wah; Hoberman, Alan M; Y Hui, Julia; Knudsen, Thomas B; Laffan, Susan B; Makris, Susan L; Martin, Matthew; McNerney, Mary Ellen; Siezen, Christine L; Stanislaus, Dinesh J; Stewart, Jane; Thompson, Kary E; Tornesi, Belen; Van der Laan, Jan Willem; Weinbauer, Gerhard F; Wood, Sandra; Piersma, Aldert H

    2016-10-21

    A database of embryo-fetal developmental toxicity (EFDT) studies of 379 pharmaceutical compounds in rat and rabbit was analyzed for species differences based on toxicokinetic parameters of area under the curve (AUC) and maximum concentration (Cmax) at the developmental lowest adverse effect level (dLOAEL). For the vast majority of cases (83% based on AUC of n = 283), dLOAELs in rats and rabbits were within the same order of magnitude (less than 10-fold different) when compared based on available data on AUC and Cmax exposures. For 13.5% of the compounds the rabbit was more sensitive and for 3.5% of compounds the rat was more sensitive when compared based on AUC exposures. For 12% of the compounds the rabbit was more sensitive and for 1.3% of compounds the rat was more sensitive based on Cmax exposures. When evaluated based on human equivalent dose (HED) conversion using standard factors, the rat and rabbit were equally sensitive. The relative extent of embryo-fetal toxicity in the presence of maternal toxicity was not different between species. Overall effect severity incidences were distributed similarly in rat and rabbit studies. Individual rat and rabbit strains did not show a different general distribution of systemic exposure LOAELs as compared to all strains combined for each species. There were no apparent species differences in the occurrence of embryo-fetal variations. Based on power of detection and given differences in the nature of developmental effects between rat and rabbit study outcomes for individual compounds, EFDT studies in two species have added value over single studies.

  14. Pathogenic microbes isolated from rabbit urine.

    PubMed

    Akinboade, O A; Adegoke, G O; Ogunji, F O; Nwufoh, K J

    1981-07-01

    Asymptomatic urinary tract infections were recovered from the urine of 40 of 100 rabbits, and identical bacteria were isolated when the rabbits were retested. Urine samples which yielded significant growths of bacteria also had pus cells. Some specimens yielded more than 2 different isolates, and staphylococci were the most frequently isolated bacteria. Oxalate and uric acid crystals were seen in 6% of the samples, particularly those with significant growths of Pseudomonas aeruginosa. No ova, parasites or fungal elements were seen in 'wet-mount' preparations and no fungi were seen when urine samples were cultured. Female rabbits showed a higher number of bacterial isolates than males. Animals with significant isolates were treated with suitable antibiotics and repeat samples yielded no growth.

  15. 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

  16. Atherogenic diet increases cholesteryl ester transfer protein messenger RNA levels in rabbit liver.

    PubMed

    Quinet, E M; Agellon, L B; Kroon, P A; Marcel, Y L; Lee, Y C; Whitlock, M E; Tall, A R

    1990-02-01

    Cholesteryl ester transfer activity is increased in plasma of cholesterol-fed rabbits. To investigate the mechanisms leading to changes in activity, we measured cholesteryl ester transfer protein (CETP) mass by RIA and CETP mRNA abundance by Northern and slot blot analysis using a human CETP cDNA probe in control (n = 8) and cholesterol-fed rabbits (n = 10). Cholesterol feeding (chow plus 0.5% cholesterol, 10% corn oil) for 30 d increased CETP mass in plasma 3.2-fold in the cholesterol-fed rabbits (12.45 +/- 0.82 micrograms/ml) compared with controls (3.86 +/- 0.38 micrograms/ml). In the hypercholesterolemic rabbit, liver CETP mRNA levels were increased 2.8 times control mRNA levels. Actin, apo E, lecithin-cholesterol acyltransferase, and albumin mRNA abundances were unchanged. In contrast to the widespread tissue distribution in humans, CETP mRNA was not detected in extrahepatic tissues of either control or cholesterol-fed animals. Using a sensitive RNase protection assay, the increase in liver CETP mRNA was detectable within 3 d of beginning the high cholesterol diet. Thus, in response to the atherogenic diet there is an early increase in liver CETP mRNA, probably causing increased CETP synthesis and secretion, and increased plasma CETP. The results indicate that the CETP gene may be regulated by diet-induced changes in lipid metabolism.

  17. Light stimulation of iris tyrosinase in vivo. [Rabbits

    SciTech Connect

    Dryja, T.P.; Kimball, G.P.; Albert, D.M.

    1980-05-01

    This paper presents evidence that light stimulates tyrosinase activity in iris melanocytes in rabbits. Levels of iris tyrosinase were found to be greater in eyes of rabbits exposed to light for 6 weeks than in eyes of rabbits maintained in darkness. Despite increasing tyrosinase levels, exposure to light produced no clinically observable change in iris color.

  18. TGF-β1 monoclonal antibody: Assessment of embryo-fetal toxicity in rats and rabbits.

    PubMed

    Hilbish, Kim G; Martin, Jennifer A; Stauber, Anja J; Edwards, Tammye L; Breslin, William J

    2016-08-01

    A humanized monoclonal antibody targeting transforming growth factor β1 (TGF-β1 mab) has been used in development for the treatment of chronic kidney disease. Embryo-fetal development studies were conducted in rats and rabbits using 30 and 25 animals per group, respectively. The TGF-β1 mab was administered subcutaneously to rats at 0, 2, or 50 mg/kg/dose on gestation days (GDs) 6, 10, and 14 and intravenously to rabbits at 0 or 3 mg/kg/dose on GDs 7, 12 to 19, and at 30 mg/kg/dose on GDs 7, 12, 14, 16, and 18. Maternal reproductive endpoints and fetal viability, weight, and morphology were evaluated. There was no indication of maternal or embryo-fetal toxicity in the rat. Effects in the rabbit were limited to the fetus where the 30 mg/kg TGF-β1 mab dose produced a slight decrease in fetal weight and an increase in the incidence of retrocaval ureter and an absent and/or malpositioned kidney/ureter in two fetuses. In conclusion, TGF-β1 mab produced no adverse maternal or embryo-fetal findings in rats when administered ≤50 mg/kg on GDs 6, 10, and 14. TGF-β1 mab did not demonstrate maternal toxicity or embryo-fetal lethality at doses as high as 30 mg/kg when administered on GDs 7, 12, 14, 16, and 18 in rabbits. Fetal growth and morphology were affected only at 30 mg/kg; thus, the no observed adverse effect level was 3 mg/kg in rabbits. The margin of safety for both rats and rabbits was ≥37-fold the clinical exposure level.

  19. Adjunctive Phosphodiesterase-4 Inhibitor Therapy Improves Antibiotic Response to Pulmonary Tuberculosis in a Rabbit Model

    PubMed Central

    Subbian, Selvakumar; Tsenova, Liana; Holloway, Jennifer; Peixoto, Blas; O'Brien, Paul; Dartois, Véronique; Khetani, Vikram; Zeldis, Jerome B.; Kaplan, Gilla

    2016-01-01

    Objectives Adjunctive host-directed therapy is emerging as a new potential approach to improve the outcome of conventional antimicrobial treatment for tuberculosis (TB). We tested the ability of a phosphodiesterase-4 inhibitor (PDE4i) CC-11050, co-administered with the first-line anti-TB drug isoniazid (INH), to accelerate bacillary killing and reduce chronic inflammation in the lungs of rabbits with experimental Mycobacterium tuberculosis (Mtb) infection. Methods A rabbit model of pulmonary TB that recapitulates the pathologic manifestations seen in humans was used. Rabbits were infected with virulent Mtb by aerosol exposure and treated for eight weeks with INH with or without CC-11050, starting at four weeks post infection. The effect of CC-11050 treatment on disease severity, pathology, bacillary load, T cell proliferation and global lung transcriptome profiles were analyzed. Results Significant improvement in bacillary clearance and reduced lung pathology and fibrosis were noted in the rabbits treated for eight weeks with INH + CC-11050, compared to those treated with INH or CC-11050 only. In addition, expression of host genes associated with tissue remodeling, tumor necrosis factor alpha (TNF-α) regulation, macrophage activation and lung inflammation networks was dampened in CC-11050-treated, compared to the untreated rabbits. Conclusions Adjunctive CC-11050 therapy significantly improves the response of rabbits with experimental pulmonary TB to INH treatment. We propose that CC-11050 may be a promising candidate for host directed therapy of patients with pulmonary TB, reducing the duration and improving clinical outcome of antibiotic treatment. PMID:26981575

  20. Reduced Arrhythmia Inducibility with Calcium/Calmodulin-Dependent Protein Kinase II Inhibition in Heart Failure Rabbits

    PubMed Central

    Hoeker, Gregory S.; Hanafy, Mohamed A.; Oster, Robert A.; Bers, Donald M.; Pogwizd, Steven M.

    2015-01-01

    Rationale Calcium/calmodulin-dependent protein kinase II (CaMKII) is activated in heart failure (HF) and can contribute to arrhythmias induced by β-adrenergic receptor-mediated sarcoplasmic reticulum calcium leak. Objective To evaluate the effect of CaMKII inhibition on ventricular tachycardia (VT) induction in conscious HF and naïve rabbits. Methods and Results Nonischemic HF was induced by aortic insufficiency and constriction. Electrocardiograms were recorded in rabbits pretreated with vehicle (saline) or the CaMKII inhibitor KN-93 (300 μg/kg); VT was induced by infusion of increasing doses of norepinephrine (NE, 1.56-25 μg/kg/min) in naïve (n = 8) and HF (n = 7) rabbits. With saline, median VT dose threshold in HF was 6.25 versus 12.5 μg/kg/min NE in naïve rabbits (p = 0.06). Pretreatment with KN-93 significantly increased VT threshold in HF and naïve rabbits (median = 25 μg/kg/min, p < 0.05 versus saline for both groups). Mean cycle length of VT initiation was shorter in HF (221 ± 20 ms) than naïve (296 ± 23 ms, p < 0.05) rabbits with saline; this difference was not significant after treatment with KN-93. Conclusions KN-93 significantly reduced arrhythmia inducibility and slowed initiation of VT, suggesting that CaMKII inhibition may have antiarrhythmic effects in the failing human heart. PMID:26650851

  1. A novel method for blood volume estimation using trivalent chromium in rabbit models

    PubMed Central

    Baby, Prathap Moothamadathil; Kumar, Pramod; Kumar, Rajesh; Jacob, Sanu S.; Rawat, Dinesh; Binu, V. S.; Karun, Kalesh M.

    2014-01-01

    Background: 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. Aims: The aim was to compare blood volume estimations using trivalent chromium [51Cr(III)] and standard Evans blue dye (EBD) method in New Zealand white rabbit models and establish correction-factor (CF). Materials and Methods: 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 51Cr(III). Twenty out of 33 rabbits were used to find CF by dividing blood volume estimation using EBD with blood volume estimation using 51Cr(III). CF is validated in 13 rabbits by multiplying it with blood volume estimation values obtained using 51Cr(III). Results: 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 51Cr(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 51Cr(III) with CF was 152.73 ± 46.25 ml or 71.87 ± 13.81 ml/kg (P = 0.11). Conclusions: The estimation of blood volume using 51Cr(III) was comparable to standard EBD method using CF. With further research in this direction, we envisage human blood volume estimation using 51Cr(III) to find its application in acute clinical settings. PMID:25190922

  2. Cell kinetics, DNA integrity, differentiation, and lipid fingerprinting analysis of rabbit adipose-derived stem cells.

    PubMed

    Barretto, Letícia Siqueira de Sá; Lessio, Camila; Sawaki e Nakamura, Ahy Natally; Lo Turco, Edson Guimarães; da Silva, Camila Gonzaga; Zambon, João Paulo; Gozzo, Fábio César; Pilau, Eduardo Jorge; de Almeida, Fernando Gonçalves

    2014-10-01

    Human adipose tissue has been described as a potential alternative reservoir for stem cells. Although studies have been performed in rabbits using autologous adipose-derived stem cells (ADSC), these cells have not been well characterized. The primary objectives of this study were to demonstrate the presence of adipose-derived stem cells isolated from rabbit inguinal fat pads and to characterize them through osteogenic and adipogenic in vitro differentiation and lipid fingerprinting analysis. The secondary objective was to evaluate cell behavior through growth kinetics, cell viability, and DNA integrity. Rabbit ADSCs were isolated to determine the in vitro growth kinetics and cell viability. DNA integrity was assessed by an alkaline Comet assay in passages 0 and 5. The osteogenic differentiation was evaluated by Von Kossa, and Alizarin Red S staining and adipogenic differentiation were assessed by Oil Red O staining. Lipid fingerprinting analyses of control, adipogenic, and osteogenic differentiated cells were performed by MALDI-TOF/MS. We demonstrate that rabbit ADSC have a constant growth rate at the early passages, with increased DNA fragmentation at or after passage 5. Rabbit ADSC viability was similar in passages 2 and 5 (90.7% and 86.6%, respectively), but there was a tendency to decreased cellular growth rate after passage 3. The ADSC were characterized by the expression of surface markers such as CD29 (67.4%) and CD44 (89.4%), using CD 45 (0.77%) as a negative control. ADSC from rabbits were successfully isolated form the inguinal region. These cells were capable to differentiate into osteogenic and adipogenic tissue when they were placed in inductive media. After each passage, there was a trend towards decreased cell growth. On the other hand, DNA fragmentation increased at each passage. ADSC had a different lipid profile when placed in control, adipogenic, or osteogenic media.

  3. Developmental toxicity studies of lumefantrine and artemether in rats and rabbits.

    PubMed

    Clark, Robert L; Youreneff, Maureen; DeLise, Anthony M

    2016-12-01

    The combination of artemether plus lumefantrine is a type of artemisinin-based combination therapy (ACT) recommended by the World Health Organization for uncomplicated falciparum malaria except in the first trimester of pregnancy. The first trimester restriction was based on the marked embryotoxicity in animals (including embryo death and cardiac and skeletal malformations) of artemisinins such as artesunate, dihydroartemisinin, and artemether. Before recommending ACTs for use in the first trimester, the World Health Organization has requested that all information relevant to the assessment of risk of ACTs to the embryo be made available to the public. This report describes the results of embryo-fetal development studies of artemether alone, lumefantrine alone, and the combination in rats and rabbits as well as toxicokinetic studies of lumefantrine in pregnant rabbits. The developmental no-effect levels for lumefantrine were 300 mg/kg/day in rats (based on a 25% decrease in litter size at 1000 mg/kg/day) and 1000 mg/kg/day in rabbits. The calculated safety margins based on human equivalent dose and plasma Cmax and AUC values were in the range of 2.5- to 17-fold. The developmental no-effect levels for artemether were 3 mg/kg/day in rats and 25 mg/kg/day in rabbits. Lumefantrine caused no teratogenicity and was not a potent embryotoxin in rats and rabbits. Expected artemisinin-like findings were seen with artemether alone and with artemether/lumefantrine combined except that no malformations were observed. There were no findings in pregnant rats and rabbits that would cause increased concern for the use of artemether-lumefantrine in the first trimester compared to other ACTs.

  4. Comparative quantitative monitoring of rabbit haemorrhagic disease viruses in rabbit kittens

    PubMed Central

    2014-01-01

    Background Only one strain (the Czech CAPM-v351) of rabbit haemorrhagic disease virus (RHDV) has been released in Australia and New Zealand to control pest populations of the European rabbit O. cuniculus. Antigenic variants of RHDV known as RHDVa strains are reportedly replacing RHDV strains in other parts of the world, and Australia is currently investigating the usefulness of RHDVa to complement rabbit biocontrol efforts in Australia and New Zealand. RHDV efficiently kills adult rabbits but not rabbit kittens, which are more resistant to RHD the younger they are and which may carry the virus without signs of disease for prolonged periods. These different infection patterns in young rabbits may significantly influence RHDV epidemiology in the field and hence attempts to control rabbit numbers. Methods We quantified RHDV replication and shedding in 4–5 week old rabbits using quantitative real time PCR to assess their potential to shape RHDV epidemiology by shedding and transmitting virus. We further compared RHDV-v351 with an antigenic variant strain of RHDVa in kittens that is currently being considered as a potential RHDV strain for future release to improve rabbit biocontrol in Australia. Results Kittens were susceptible to infection with virus doses as low as 10 ID50. Virus growth, shedding and transmission after RHDVa infection was found to be comparable or non-significantly lower compared to RHDV. Virus replication and shedding was observed in all kittens infected, but was low in comparison to adult rabbits. Both viruses were shed and transmitted to bystander rabbits. While blood titres indicated that 4–5 week old kittens mostly clear the infection even in the absence of maternal antibodies, virus titres in liver, spleen and mesenteric lymph node were still high on day 5 post infection. Conclusions Rabbit kittens are susceptible to infection with very low doses of RHDV, and can transmit virus before they seroconvert. They may therefore play an important

  5. Highly potent VEGF-A-antagonistic DARPins as anti-angiogenic agents for topical and intravitreal applications.

    PubMed

    Stahl, Andreas; Stumpp, Michael T; Schlegel, Anja; Ekawardhani, Savira; Lehrling, Christina; Martin, Gottfried; Gulotti-Georgieva, Maya; Villemagne, Denis; Forrer, Patrik; Agostini, Hansjürgen T; Binz, H Kaspar

    2013-01-01

    The next-generation ophthalmic anti-VEGF therapeutics must aim at being superior to the currently available agents with regard to potency and improved drug delivery, while still being stable and safe to use at elevated concentrations. We show here the generation of a set of highly potent VEGF-A antagonistic DARPins (designed ankyrin repeat proteins) delivering these properties. DARPins with single-digit picomolar affinity to human VEGF-A were generated using ribosome display selections. Specific and potent human VEGF-A binding was confirmed by ELISA and endothelial cell sprouting assays. Cross-reactivity with VEGF-A of several species was confirmed by ELISA. Intravitreally injected DARPin penetrated into the retina and reduced fluorescein extravasation in a rabbit model of vascular leakage. In addition, topical DARPin application was found to diminish corneal neovascularization in a rabbit suture model, and to suppress laser-induced neovascularization in a rat model. Even at elevated doses, DARPins were safe to use. The fact that several DARPins are highly active in various assays illustrates the favorable class behavior of the selected binders. Anti-VEGF-A DARPins thus represent a novel class of highly potent and specific drug candidates for the treatment of neovascular eye diseases in both the posterior and the anterior eye chamber.

  6. An in vitro study of hematopoietic progenitor cells from peripheral blood of rabbits

    PubMed Central

    2005-01-01

    Abstract The purpose of this study was to isolate and cultivate a subpopulation of pluripotent stem cells (PSCs) from the peripheral blood of rabbits, which are frequently used in veterinary research as an animal model. Pluripotent stem cells, as described in human beings, are fibroblast-like cells that exhibit a CD34 marker, specific from other hematopoietic stem cells. Commonly used human commercial media has been researched for culturing rabbit PSCs. These findings allow us to contemplate the direct application of this simple and standardized methodology in several areas of study, such as of the pharmacological effect of many drugs on hematopoietic cells, veterinary practice, and even the study of new strategies in cellular therapy for some human diseases. PMID:16479731

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

    PubMed

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

    2013-06-01

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

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

    PubMed Central

    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. PMID:27034393

  9. Pseudogenization of the MCP-2/CCL8 chemokine gene in European rabbit (genus Oryctolagus), but not in species of Cottontail rabbit (Sylvilagus) and Hare (Lepus)

    PubMed Central

    2012-01-01

    Background Recent studies in human have highlighted the importance of the monocyte chemotactic proteins (MCP) in leukocyte trafficking and their effects in inflammatory processes, tumor progression, and HIV-1 infection. In European rabbit (Oryctolagus cuniculus) one of the prime MCP targets, the chemokine receptor CCR5 underwent a unique structural alteration. Until now, no homologue of MCP-2/CCL8a, MCP-3/CCL7 or MCP-4/CCL13 genes have been reported for this species. This is interesting, because at least the first two genes are expressed in most, if not all, mammals studied, and appear to be implicated in a variety of important chemokine ligand-receptor interactions. By assessing the Rabbit Whole Genome Sequence (WGS) data we have searched for orthologs of the mammalian genes of the MCP-Eotaxin cluster. Results We have localized the orthologs of these chemokine genes in the genome of European rabbit and compared them to those of leporid genera which do (i.e. Oryctolagus and Bunolagus) or do not share the CCR5 alteration with European rabbit (i.e. Lepus and Sylvilagus). Of the Rabbit orthologs of the CCL8, CCL7, and CCL13 genes only the last two were potentially functional, although showing some structural anomalies at the protein level. The ortholog of MCP-2/CCL8 appeared to be pseudogenized by deleterious nucleotide substitutions affecting exon1 and exon2. By analyzing both genomic and cDNA products, these studies were extended to wild specimens of four genera of the Leporidae family: Oryctolagus, Bunolagus, Lepus, and Sylvilagus. It appeared that the anomalies of the MCP-3/CCL7 and MCP-4/CCL13 proteins are shared among the different species of leporids. In contrast, whereas MCP-2/CCL8 was pseudogenized in every studied specimen of the Oryctolagus - Bunolagus lineage, this gene was intact in species of the Lepus - Sylvilagus lineage, and was, at least in Lepus, correctly transcribed. Conclusion The biological function of a gene was often revealed in situations of

  10. Evaluation of mycobacterial virulence using rabbit skin liquefaction model.

    PubMed

    Zhang, Guoping; Zhu, Bingdong; Shi, Wanliang; Wang, Mingzhu; Da, Zejiao; Zhang, Ying

    2010-01-01

    Liquefaction is an important pathological process that can subsequently lead to cavitation where large numbers of bacilli can be coughed up which in turn causes spread of tuberculosis in humans. Current animal models to study the liquefaction process and to evaluate virulence of mycobacteria are tedious. In this study, we evaluated a rabbit skin model as a rapid model for liquefaction and virulence assessment using M. bovis BCG, M. tuberculosis avirulent strain H37Ra, M. smegmatis, and the H37Ra strains complemented with selected genes from virulent M. tuberculosis strain H37Rv. We found that with prime and/or boosting immunization, all of these live bacteria at enough high number could induce liquefaction, and the boosting induced stronger liquefaction and more severe lesions in shorter time compared with the prime injection. The skin lesions caused by high dose live BCG (5×10 (6) ) were the most severe followed by live M. tuberculosis H37Ra with M. smegmatis being the least pathogenic. It is of interest to note that none of the above heat-killed mycobacteria induced liquefaction. When H37Ra was complemented with certain wild type genes of H37Rv, some of the complemented H37Ra strains produced more severe skin lesions than H37Ra. These results suggest that the rabbit skin liquefaction model can be a more visual, convenient, rapid and useful model to evaluate virulence of different mycobacteria and to study the mechanisms of liquefaction.

  11. Contact lenses in extreme cold environments: response of rabbit corneas.

    PubMed

    Socks, J F

    1982-04-01

    Contact lenses are worn by many individuals in military and civilian populations. Anecdotal reports have described contact lenses "sticking" and "freezing" to the eye during extreme cold conditions. However, some articles indicate the advantages of wearing contact lenses in cold environments. Military operations frequently taken place in cold regions; therefore, we need to known whether contact lenses can be worn safely in extreme cold. Rabbits were fitted with hard (polymethyl methacrylate) contact lenses and exposed to -28.9 degrees C temperatures with winds up to 78 mph (125 km/hr) for 3-hr periods. The wind-chill factor in these conditions exceeded -67.8 degrees C. No effects of the cold or contact lenses were seen in 85% of the eyes. A few of the eyes, both with contact lenses and without, showed mild superficial fluorescein staining of the cornea which cleared within a few ours after exposure. Histologic examination of the corneas revealed no abnormalities attributable to the cold. Inasmuch as this study showed that rabbits wearing contact lenses in extreme cold suffered no acute deleterious effects to the eyes, the research can be expanded to include human subjects.

  12. Endoscopic laser reshaping of rabbit tracheal cartilage: preliminary investigations

    NASA Astrophysics Data System (ADS)

    Tsang, Walter; Lam, Anthony; Protsenko, Dmitry; Wong, Brian J.

    2005-04-01

    Background: Tracheal cartilage deformities due to trauma, prolonged endotracheal intubation or infection are difficult to correct. Current treatment options such as dilation, laser ablation, stent placement, and segmental resection are only temporary or carry significant risks. The objectives of this project were to design and test a laser activated endotracheal stent system that can actively modify the geometry of tracheal cartilage, leading to permanent retention of a new and desirable tracheal geometry. Methods: Ex vivo rabbit tracheal cartilage (simulating human neonate trachea) were irradiated with an Er: Glass laser, (λ= 1.54um, 0.5W-2.5W, 1 sec to 5 sec). Shape change and gross thermal injury were assessed visually to determine the best laser power parameters for reshaping. A rigid endoscopic telescope and hollow bronchoscope were used to record endoscopic images. The stent was constructed from nitinol wire, shaped into a zigzag configuration. An ex vivo testing apparatus was also constructed. Results: The best laser power parameter to produce shape change was 1 W for 6-7 seconds. At this setting, there was significant shape change with only minimal thermal injury to the tracheal mucosa, as assessed by visual inspection. The bronchoscopy system functioned adequately during testing in the ex vivo testing apparatus. Conclusion: We have successfully designed instrumentation and created the capability to endoscopically reshape tracheal cartilage in an ex vivo rabbit model. The results obtained in ex vivo tracheal cartilage indicated that reshaping using Er: Glass laser can be accomplished.

  13. Structural changes in rabbit oral epithelium caused by zinc deficiency.

    PubMed

    Joseph, C E; Ashrafi, S H; Waterhouse, J P

    1981-01-01

    We report the successful establishment of zinc deficiency in rabbits by dietary means. The soybean protein of a standard rabbit diet was replaced by egg albumin. Weanling, New Zealand white rabbits, were fed a low zinc diet containing 1.5 microgram Zn/g of diet. Zinc-deficient rabbits showed stunted growth, weight loss, altered posture, partial alopecia and crusting of skin. Structural alterations in oral epithelium of the zinc-deficient rabbits included in the tongue flattened filiform papillae showing parakeratosis, in the cheek parakeratosis of the normally nonkeratinized epithelium and hyperplasia of the lip epidermis.

  14. Comparison of silver nitrate and tetracycline as pleural sclerosing agents in rabbits.

    PubMed

    Vargas, F S; Teixeira, L R; Silva, L M; Carmo, A O; Light, R W

    1995-10-01

    The ideal agent to produce pleurodesis has not been identified. Tetracycline, the drug used most commonly in the 1980s, is no longer available. Talc either aerosolized or in a slurry is the agent used just most commonly at the present time, but there are concerns about its safety. Another possibility is silver nitrate, which was widely used in the past, but was abandoned on account of side effects. We hypothesized that lower concentrations of silver nitrate than had been used in the past would be effective in creating a pleurodesis in rabbits. The following medications in a total volume of 2 mL were instilled intrapleurally in three groups of ten anesthetized rabbits: 0.25% or 0.50% silver nitrate and 35 mg/kg tetracycline. Twenty-eight days after the injection, the animals were sacrificed and the pleural spaces were assessed grossly for evidence of pleurodesis and microscopically for evidence of fibrosis and inflammation. The intrapleural injection of 0.50% silver nitrate produced an effective pleurodesis. The mean degree of gross pleurodesis in the rabbits that received 0.50% silver nitrate (3.4 +/- 1.2) did not differ significantly from that of the rabbits that received tetracycline (3.5 +/- 0.7) (scale 0 to 4). The mean degree of microscopic pleural fibrosis in the rabbits that received 0.50% silver nitrate (3.4 +/- 0.7) did not differ significantly from that of the rabbits that received tetracycline (3.9 +/- 0.3). However, 0.25% silver nitrate was ineffective in creating pleural fibrosis, either grossly or microscopically. No rabbits died after the intrapleural injection of the drugs. There were no observed side effects after the injection of silver nitrate. The present study demonstrates that 0.50% silver nitrate instilled into the pleural space is an effective agent for producing pleurodesis in the rabbit; its effect is comparable to tetracycline 35 mg/kg. This agent should be compared with tetracycline derivatives and talc in studies in humans.

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

    PubMed

    Zheng, Tao; Parkes, John P

    2011-12-15

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

  16. Angiogenesis in Pituitary Adenomas: Human Studies and New Mutant Mouse Models

    PubMed Central

    Cristina, Carolina; Demarchi, Gianina; Lopez Vicchi, Felicitas; Perez Millan, Maria Ines; Perrone, Sofia; Ornstein, Ana Maria; Berner, Silvia Inés; Becu-Villalobos, Damasia

    2014-01-01

    The role of angiogenesis in pituitary tumor development has been questioned, as pituitary tumors have been usually found to be less vascularized than the normal pituitary tissue. Nevertheless, a significantly higher degree of vasculature has been shown in invasive or macropituitary prolactinomas when compared to noninvasive and microprolactinomas. Many growth factors and their receptors are involved in pituitary tumor development. For example, VEGF, FGF-2, FGFR1, and PTTG, which give a particular vascular phenotype, are modified in human and experimental pituitary adenomas of different histotypes. In particular, vascular endothelial growth factor, VEGF, the central mediator of angiogenesis in endocrine glands, was encountered in experimental and human pituitary tumors at different levels of expression and, in particular, was higher in dopamine agonist resistant prolactinomas. Furthermore, several anti-VEGF techniques lowered tumor burden in human and experimental pituitary adenomas. Therefore, even though the role of angiogenesis in pituitary adenomas is contentious, VEGF, making permeable pituitary endothelia, might contribute to adequate temporal vascular supply and mechanisms other than endothelial cell proliferation. The study of angiogenic factor expression in aggressive prolactinomas with resistance to dopamine agonists will yield important data in the search of therapeutical alternatives. PMID:25505910

  17. Angiogenesis in pituitary adenomas: human studies and new mutant mouse models.

    PubMed

    Cristina, Carolina; Luque, Guillermina María; Demarchi, Gianina; Lopez Vicchi, Felicitas; Zubeldia-Brenner, Lautaro; Perez Millan, Maria Ines; Perrone, Sofia; Ornstein, Ana Maria; Lacau-Mengido, Isabel M; Berner, Silvia Inés; Becu-Villalobos, Damasia

    2014-01-01

    The role of angiogenesis in pituitary tumor development has been questioned, as pituitary tumors have been usually found to be less vascularized than the normal pituitary tissue. Nevertheless, a significantly higher degree of vasculature has been shown in invasive or macropituitary prolactinomas when compared to noninvasive and microprolactinomas. Many growth factors and their receptors are involved in pituitary tumor development. For example, VEGF, FGF-2, FGFR1, and PTTG, which give a particular vascular phenotype, are modified in human and experimental pituitary adenomas of different histotypes. In particular, vascular endothelial growth factor, VEGF, the central mediator of angiogenesis in endocrine glands, was encountered in experimental and human pituitary tumors at different levels of expression and, in particular, was higher in dopamine agonist resistant prolactinomas. Furthermore, several anti-VEGF techniques lowered tumor burden in human and experimental pituitary adenomas. Therefore, even though the role of angiogenesis in pituitary adenomas is contentious, VEGF, making permeable pituitary endothelia, might contribute to adequate temporal vascular supply and mechanisms other than endothelial cell proliferation. The study of angiogenic factor expression in aggressive prolactinomas with resistance to dopamine agonists will yield important data in the search of therapeutical alternatives.

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

    PubMed

    Gall, A; Schirrmeier, H

    2006-10-01

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

  19. 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.

  20. International Conference on Immunogenetics of the Rabbit.

    DTIC Science & Technology

    1983-12-09

    DISRMUTION STAMP 83 12 19 001 DATE RECEIVED IN DTIC PHOTOGRAPH THIS SHEET AND RETURN TO DTIC-DDA-2 FORM DOCUMENT PROCESSING SHEETDTIC OCT 79 70A...DNA pox virus which is a recombinant between Shope fibroma and Shope myxoma viruses. The meeting reinforced the idea that the rabbit, historically of

  1. Comedogenicity of sunscreens. Experimental observations in rabbits.

    PubMed

    Mills, O H; Kligman, A M

    1982-06-01

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

  2. Mathematical Modeling in a Feast of Rabbits.

    ERIC Educational Resources Information Center

    Jones, Graham A.

    1993-01-01

    Solves the problem of the reproduction of rabbit pairs utilizing the Fibonacci sequence. Examines modified versions of the problem, and presents a vignette of one modification based on the author's experience in using the approach with preservice middle school teachers. Extends the approach to other related problems. (MDH)

  3. Intrauterine infection induces programmed cell death in rabbit periventricular white matter.

    PubMed

    Debillon, T; Gras-Leguen, C; Vérielle, V; Winer, N; Caillon, J; Rozé, J C; Gressens, P

    2000-06-01

    An association between chorioamnionitis and periventricular leukomalacia has been reported in human preterm infants. However, whether this link is causal has not been convincingly established, and the underlying molecular mechanisms remain unclear. The objective of this study was to establish a reproducible model of cerebral white matter disease in preterm rabbits after intrauterine infection. Escherichia coli was inoculated into both uterine horns of laparotomized pregnant rabbits when gestation was 80% complete. The fetuses were delivered by cesarean section and killed 12, 24, or 48 h after the inoculation. Programmed cell death in the white matter was evaluated by hematoxylin-eosin-saffron staining and in situ fragmented DNA labeling (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling). In a first group of 14 pregnant rabbits not treated with antibiotics, all fetuses delivered 48 h after inoculation were stillborn, whereas fetuses extracted 12 or 24 h after inoculation were alive. No significant cell death was detected in the live fetuses compared with the control noninfected rabbits. In a second group of five pregnant rabbits treated with ceftriaxone initiated 24 h after the inoculation and continued until cesarean section was performed 48 h after inoculation, 13 fetuses were alive, but all showed evidence of extensive programmed cell death in the white matter by hematoxylin-eosin-saffron staining and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling. White matter damage became histologically detectable only 48 h after inoculation. Three of the 13 brains displayed periventricular white matter cysts mimicking human cystic periventricular leukomalacia. The high reproducibility of white matter damage in our model should permit further studies aimed at unraveling the molecular mechanisms of periventricular leukomalacia.

  4. Fumarylacetoacetate Hydrolase Knock-out Rabbit Model for Hereditary Tyrosinemia Type 1*

    PubMed Central

    Li, Li; Zhang, Quanjun; Yang, Huaqiang; Zou, Qingjian; Lai, Chengdan; Jiang, Fei; Zhao, Ping; Luo, Zhiwei; Yang, Jiayin; Chen, Qian; Wang, Yan; Newsome, Philip N.; Frampton, Jon; Maxwell, Patrick H.; Li, Wenjuan; Chen, Shuhan; Wang, Dongye; Siu, Tak-Shing; Tam, Sidney; Tse, Hung-Fat; Qin, Baoming; Bao, Xichen; Esteban, Miguel A.; Lai, Liangxue

    2017-01-01

    Hereditary tyrosinemia type 1 (HT1) is a severe human autosomal recessive disorder caused by the deficiency of fumarylacetoacetate hydroxylase (FAH), an enzyme catalyzing the last step in the tyrosine degradation pathway. Lack of FAH causes accumulation of toxic metabolites (fumarylacetoacetate and succinylacetone) in blood and tissues, ultimately resulting in severe liver and kidney damage with onset that ranges from infancy to adolescence. This tissue damage is lethal but can be controlled by administration of 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), which inhibits tyrosine catabolism upstream of the generation of fumarylacetoacetate and succinylacetone. Notably, in animals lacking FAH, transient withdrawal of NTBC can be used to induce liver damage and a concomitant regenerative response that stimulates the growth of healthy hepatocytes. Among other things, this model has raised tremendous interest for the in vivo expansion of human primary hepatocytes inside these animals and for exploring experimental gene therapy and cell-based therapies. Here, we report the generation of FAH knock-out rabbits via pronuclear stage embryo microinjection of transcription activator-like effector nucleases. FAH−/− rabbits exhibit phenotypic features of HT1 including liver and kidney abnormalities but additionally develop frequent ocular manifestations likely caused by local accumulation of tyrosine upon NTBC administration. We also show that allogeneic transplantation of wild-type rabbit primary hepatocytes into FAH−/− rabbits enables highly efficient liver repopulation and prevents liver insufficiency and death. Because of significant advantages over rodents and their ease of breeding, maintenance, and manipulation compared with larger animals including pigs, FAH−/− rabbits are an attractive alternative for modeling the consequences of HT1. PMID:28053091

  5. Catalpol ameliorates diabetic atherosclerosis in diabetic rabbits

    PubMed Central

    Liu, Jiang-Yue; Zheng, Chen-Zhao; Hao, Xin-Ping; Zhang, Dai-Juan; Mao, An-Wei; Yuan, Ping

    2016-01-01

    Catalpol, isolated from the roots of Rehmanniaglutinosa, Chinese foxglove, is an iridoid glycoside with antioxidant, anti-inflammatory and anti-hyperglycemic agent. The present study was to investigate the effects of catalpol on diabetic atherosclerosis in alloxan-induced diabetic rabbits. Diabetes was induced in rabbits by a hyperlipidemic diet and intravenous injection of alloxan (100 mg/kg). Rabbits were treated for 12 weeks. The fasting blood glucose, insulin, homeostasis model of insulin resistance, total cholesterol and triglyceride were measured. The thoracic aorta was excised for histology. The plasma and vascular changes including some markers of oxidative stress, inflammatory cytokines and fibrosis factors were examined. Plasma levels of fasting blood glucose, insulin and homeostasis model of insulin resistance were significantly decreased in catalpol group. Catalpol treatment ameliorated diabetic atherosclerosis in diabetic rabbits as demonstrated by significantly inhibited neointimal hyperplasia and macrophages recruitment. Catalpol treatment also enhanced the activities of superoxide dismutase, glutathione peroxidase, and increased the plasma levels of total antioxidant status, meanwhile reduced the levels of malondialdehyde, protein carbonyl groups and advanced glycation end product. Furthermore, catalpol also reduced circulating levels of tumor necrosis factor-α, monocyte chemotactic protein-1 and vascular cell adhesion molecule-1. Catalpol also decreased transforming growth factor-β1 and collagen IV mRNA and protein expressions in the vessels. Catalpol exerts an ameliorative effect on atherosclerotic lesion in alloxan-induced diabetic rabbits. The possible mechanisms may be related to inhibition of oxidative stress inflammatory response and anti-fibrosis and reduced aggregation of extracellular matrix. PMID:27830011

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

    PubMed

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

    2014-01-01

    Rabbit hepatitis E virus (HEV) is a novel genotype of HEV, and is considered to pose a risk of zoonotic transmission. Research into the systemic distribution of rabbit HEV in rabbits during different periods of infection has rarely been reported. To better understand this virus, we infected rabbits with second-passage rabbit HEV via an intraperitoneal route. After inoculation, the infection showed two types, temporary and constant infection. The detection of HEV RNA in the feces varied with time, and serum antigen correlated with fecal HEV RNA. Viremia only appeared 72 days after inoculation. The rabbits remained antibody negative throughout the experimental period. When HEV was localized, several organs besides the liver were HEV RNA positive. Tissue antigen was observed immunohistochemically in the different cells of various organs, especially in parts of the small intestine and the characteristic rabbit gut-associated lymphoid tissue. These data provide valuable information for future research into the pathogenesis of HEV.

  7. The potential impact of new generation transgenic methods on creating rabbit models of cardiac diseases.

    PubMed

    Bősze, Z; Major, P; Baczkó, I; Odening, K E; Bodrogi, L; Hiripi, L; Varró, A

    2016-07-01

    Since the creation of the first transgenic rabbit thirty years ago, pronuclear microinjection remained the single applied method and resulted in numerous important rabbit models of human diseases, including cardiac deficiencies, albeit with low efficiency. For additive transgenesis a novel transposon mediated method, e.g., the Sleeping Beauty transgenesis, increased the efficiency, and its application to create cardiac disease models is expected in the near future. The targeted genome engineering nuclease family, e.g., the zink finger nuclease (ZFN), the transcription activator-like effector nuclease (TALEN) and the newest, clustered regularly interspaced short palindromic repeats (CRISPR) with the CRISPR associated effector protein (CAS), revolutionized the non-mouse transgenesis. The latest gene-targeting technology, the CRISPR/CAS system, was proven to be efficient in rabbit to create multi-gene knockout models. In the future, the number of tailor-made rabbit models produced with one of the above mentioned methods is expected to exponentially increase and to provide adequate models of heart diseases.

  8. Genotyping and DNA microarray based characterization of Staphylococcus aureus isolates from rabbit carcasses.

    PubMed

    Merz, Axel; Stephan, Roger; Johler, Sophia

    2016-02-01

    Staphylococcus aureus can cause staphylococcal food poisoning. Although the organism is frequently detected on rabbit carcasses, little is known about the characteristics of S. aureus strains contaminating rabbit meat. In this study, 137 S. aureus isolates originating from 137 rabbit carcasses were spa typed and characterized by DNA microarray. The isolates were assigned to CC5, CC7, CC8, CC15, CC96, CC101, CC121, and ST890, and to 13 spa types (t056, t085, t091, t160, t179, t681, t741, t745, t1190, t1773, t4770, t8456, t14871). Enterotoxin genes detected included sea, sed, sej, and ser. In addition, the egc operon, encoding the newly described staphylococcal enterotoxins SEG/SEI/SElM/SElN/SElO/SElU, was found in all isolates except those of t091. While none of the examined isolates presented genes conferring methicillin, vancomycin, or aminoglycoside resistance, we frequently detected blaZ/I/R conferring resistance to penicillin. The isolates represented a heterogeneous group assigned to clonal lineages detected among humans and animals, with two spa types exclusively associated with rabbit meat (t4770, t8456).

  9. Exploring transplacental transmission of Pneumocystis oryctolagi in first-time pregnant and multiparous rabbit does.

    PubMed

    Sanchez, Catherine A; Chabé, Magali; Aliouat, El Moukhtar; Durand-Joly, Isabelle; Gantois, Nausicaa; Conseil, Valérie; López, Claudia; Duriez, Thérèse; Dei-Cas, Eduardo; Vargas, Sergio L

    2007-12-01

    Pneumocystis sp. is transmitted through the airborne route and presents a high host-species-specificity. Occasional reports of Pneumocystis pneumonia in still births and newborn infants suggest that other routes of transmission, e.g. transplacental might occur. The latter has been reported in rabbits but available data indicate that transplacental transmission of Pneumocystis seems not to occur in corticosteroid-treated rats and in SCID mice. The present study was undertaken to evaluate transplacental transmission of Pneumocystis oryctolagi. The spontaneously-acquired pneumocystosis rabbit model using hybrid California/New Zealand white female rabbits was selected because of similarities among rabbit and human placentas. Three different experiments were conducted in France and Chile. Pneumocystis organisms were detected by microscopy in the lungs of pregnant does and Pneumocystis DNA was found in the lungs of fetuses from the multiparous does from the second week to the end of gestation. Pneumocystis DNA was not detected in fetuses from primiparous does. Detection of Pneumocystis oryctolagi--DNA in fetuses of multiparous does and not in those of primiparous ones, suggests that transplacental transmission may be favored by multiple gestations. Whether Pneumocystis-DNA in fetal tissues from multiparous does resulted from transplacental passage of viable transmissible forms requires further investigation.

  10. 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.

  11. Amplification of rabbit hepatocyte growth factor and detection of its expression in COS-7 cell line.

    PubMed

    Yao, H; Han, J; Wang, J; Wang, L; Gong, C; Li, L; Liang, Z; Tian, Y

    2015-11-25

    We used RT-PCR, nested PCR to acquire the partial 5'- race fragment of rabbit HGF cDNA and the partial 3'- race fragment of rabbit HGF cDNA. Then, we used recombination PCR to acquire rabbit HGF successfully. Homology analysis was conducted among the sequence of RABHGF and known human and rat HGF by DNAStar. It was proved that high level of homology existed among the sequences of those three HGF genes. We used the acquired gene of RABHGF to construct its recombinant eukaryotic expression vector pcDNA3.1(+)-RABHGF (pRABHGF). The identification of the eukaryotic expression vector pRABHGF by PCR, restriction enzyme and sequencing analysis showed that rabbit HGF gene was correctly inserted into the vector. pRABHGF and pcDNA3.1(+) as controls were transfected into COS-7 cells by lipofectamine. It takes 24h-36h after transfection to detect the expression of RABHGF protein by indirect immunofluorescence assay (IFA). The proliferation of cos-7 cells were evaluated by MTT assay. The result displayed positive effect of RABHGF protein on the proliferation of COS-7 cells. This study lays the foundation for a new gene therapy method for ischemic heart disease.

  12. Early effect of a single intravenous injection of ethanol on hepatic sinusoidal endothelial fenestrae in rabbits

    PubMed Central

    Jacobs, Frank; Wisse, Eddie; De Geest, Bart

    2009-01-01

    Background It has been postulated that ethanol affects hepatic sinusoidal and perisinusoidal cells. In the current experimental study, we investigated the early effect of a single intravenous dose of ethanol on the diameter of liver sinusoidal endothelial fenestrae in New Zealand White rabbits. The diameter of fenestrae in these rabbits is similar to the diameter found in humans with healthy livers. The effect of ethanol on the size of fenestrae was studied using transmission electron microscopy, because plastic embedding provides true measures for the diameter of fenestrae. Results After intravenous administration of a single dose of 0.75 g/kg, ethanol concentration peaked at 1.1 ± 0.10 g/l at ten minutes after injection. Compared to control rabbits (103 ± 1.1 nm; n = 8), the average diameter of fenestrae in ethanol-injected rabbits determined at 10 minutes after injection was significantly (p < 0.01) smaller (96 ± 2.2 nm; n = 5). Detailed analysis of distribution histograms of the diameters of fenestrae showed that the effect of ethanol was highly homogeneous. Conclusion A decrease of the diameter of fenestrae 10 minutes after ethanol administration is likely the earliest morphological alteration induced by ethanol in the liver and underscores the potential role of liver sinusoidal endothelial cells in alcoholic liver injury. PMID:19594919

  13. The penetration of topically applied ointment containing hyaluronic acid in rabbit tissues.

    PubMed

    Birkenfeld, B; Parafiniuk, M; Bielecka-Grzela, S; Klimowicz, A; Piwowarska-Bilska, H; Mikołajczak, R; Listewnik, M H; Kurzejamska-Parafiniuk, M; Osowski, A; Byszewska-Szpocińska, E

    2011-01-01

    The properties of hyaluronic acid used for treatment of acute and chronic joint disease are known for many years and this compound is widely used both in humans and animals. To obtain a therapeutic effect of a certain drug, the appropriate concentration in the target organ or tissue is important. The application of labeled compounds is one of the frequently applied techniques to estimate drug penetration into the skin and other body tissues or organs. The aim of the study was to evaluate the penetration of hyaluronic acid labeled with I-131 through the skin and its distribution within the knee joint and other internal organs in rabbits after a topical application of an ointment containing hyaluronic acid. The experiment was performed on 22 albino rabbits divided into control and examined groups. Fifteen rabbits were exposed to the multicomponent ointment containing hyaluronic acid labeled with I-131. Time of exposure was 48 hours. Hyaluronate penetrated to a high degree into the examined tissues. No significant differences in terms of leg tissue activity were observed between a leg tissue exposed to labeled ointment and that unexposed, suggesting that after topical administration, the active component of the ointment is delivered to the joint via the blood stream. Hyaluronate applied topically penetrates through the skin into the rabbit tissues and organs and into the joint fluid of both legs (exposed and not exposed). This route of administration seems to be useful for this drug delivery and allows to avoid unnecessary side effects.

  14. Disseminated histoplasmosis (Histoplasma capsulatum) in a pet rabbit: case report and review of the literature.

    PubMed

    Brandão, João; Woods, Samantha; Fowlkes, Natalie; Leissinger, Mary; Blair, Robert; Pucheu-Haston, Cherie; Johnson, James; Elster Phillips, Christina; Tully, Thomas

    2014-01-01

    A 2.5-year-old intact male miniature lop rabbit (Oryctolagus cuniculus) was presented with multiple nodules surrounding the eyes, nose, mouth, and prepuce. Cytological evaluation of the periocular nodules revealed the presence of intracellular (within macrophages) and extracellular yeast organisms. The yeast organisms were approximately 3-5 µm in diameter, round to oval, with a thin clear capsule, and contained an eccentrically placed basophilic crescent-shaped nucleus. The clinical pathological interpretation was granulomatous inflammation with intralesional yeast of a morphology consistent with Histoplasma spp. The rabbit was treated with microsized griseofulvin (25 mg/kg, orally, once a day) for 12 days pending final cytological diagnosis of histoplasmosis. No significant improvement was noted during the treatment period, and humane euthanasia was performed. Postmortem examination revealed the presence of intracellular and extracellular yeast organisms in the small intestine, skin (antebrachium, perioral, palpebral, perianal, and pinnal), penis, penile urethra, rectum, axillary lymph node, and conjunctiva. Postmortem fungal culture yielded Histoplasma capsulatum. Based on clinical and postmortem findings, a definitive diagnosis of disseminated histoplasmosis was made. Disseminated histoplasmosis appears to be unreported in rabbits. Although the treatment used did not provide noticeable improvement, available information on histoplasmosis treatment in other species has been reviewed to provide useful information for future management of this condition in rabbits.

  15. Prevention of Acoustic Trauma-Induced Hearing Loss by N-acetylcysteine Administration in Rabbits

    PubMed Central

    Motalebi Kashani, Masoud; Saberi, Hamidreza; Hannani, Mitra

    2013-01-01

    Background Acoustic trauma is an injury to the hearing mechanisms in the inner ear due to excessive noise. This injury is the most prevalent cause of sensorineural hearing loss in humans, especially from occupational exposure. Previous studies have shown the essential role of free radical formation in the inner ear hearing loss caused by acoustic trauma. Objectives This study was performed to determine the effect of N-acetylcysteine (NAC) administration for reducing acute acoustic trauma in rabbits. Materials and Methods Twenty four rabbits were assigned to four groups including: control, noise plus saline, noise plus NAC administration (325 mg/kg body weight by intraperitoneal injection (IP), three days before exposure to noise and three days after noise exposure), and NAC alone. Auditory brain stem response (ABR) threshold was measured before exposure and one hour and 14 days after exposure. Results The saline plus noise group had on average a 49 decibel (dB) temporary threshold shift (TTS) and 23.9 dB permanent threshold shift (PTS) at the studied frequencies, while rabbits in the NAC administration plus noise group had a 31.5 dB TTS and 10.7 dB PTS averaged across the frequencies. Conclusions Administration of NAC can provide appropriate protection against acoustic trauma-induced hearing loss in rabbits at all studied frequencies. PMID:24396768

  16. Crossbreeding effects on rabbit reproduction from four maternal lines of rabbits.

    PubMed

    Ragab, M; Sánchez, J P; Mínguez, C; Baselga, M

    2016-07-01

    Litter size is essential for an efficient production of rabbit meat. A diallel cross between four maternal lines was carried out and the analysis of the components of litter size has been already done. This paper presents the analysis of litter size traits themselves (total born (TB), number born alive (NBA), number weaned (NW)) and kindling interval (KI), that complete the analysis of the reproductive performance. The 16 genetic groups were distributed in four Spanish farms. The V line was present in all farms in order to be used as reference group. A total of 34 546 parities from 7111 does, were analysed. The crossbreeding parameters were estimated according to Dickerson model. The differences between lines performance were of low magnitude and not significant for litter size traits. The LP line showed the shortest KI followed by H respect to lines A and V. These differences reflected the differences between direct and maternal genetic effects. The differences between the average of all crosses and line V were found to be significant and seemed to be important, being 0.46 for TB, 0.56 for NBA, 0.75 for NW and -2.21 days for KI. The differences between reciprocal crosses for litter size were of low magnitude and non-significant, which indicate that the maternal effects are not important between these lines. In general, the lines did not show significant differences in direct and maternal genetic effects for TB, NBA and NW but there were some significant differences for KI, which ranged from 1.54 to 6.85 days in direct effects and from 0.63 to 3.38 days for maternal effects. A positive and, in some cases, relevant heterosis was found. The largest heterosis was for TB in the HV cross (1.05 rabbits), followed by the AH (0.74 rabbits), AV (0.57 rabbits) and LH (0.55 rabbits) crosses. For NBA, significant heterosis was found in HV (1.11 rabbits) and AV (0.49 rabbits) and for NW in AV (0.90 rabbits), LH (0.70 rabbits) and LV (0.58 rabbits). Favourable and significant

  17. A proposed model of naturally occurring osteoarthritis in the domestic rabbit.

    PubMed

    Arzi, Boaz; Wisner, Erik R; Huey, Daniel J; Kass, Philip H; Hu, Jerry; Athanasiou, Kyriacos A

    2011-12-19

    Osteoarthritis affects one in eight American adults over the age of 25 y and is a leading cause of chronic disability in the US. Translational research to investigate treatments for this naturally occurring joint disease requires an appropriate animal model. The authors conducted a retrospective study to assess the potential of naturally occurring osteoarthritis in the domestic rabbit as a model of the human disease. Analysis of radiographic images showed that the presence and severity of osteoarthritis were significantly influenced by both age and body weight. The most commonly affected joints were the knee and the hip. The findings reported here suggest that the rabbit is an excellent model of spontaneously arising osteoarthritis that may be useful in translational research pertaining to the human disease.

  18. Molecular detection of Bartonella alsatica in European wild rabbits (Oryctolagus cuniculus) in Andalusia (Spain).

    PubMed

    Márquez, Francisco J

    2010-10-01

    A sample of 279 European wild rabbits, Oryctolagus cuniculus (141 males, 138 females), captured alive in Andalusia (Spain) and belonging to the two haplotype classes previously described for this species (230 and 49 corresponding with haplotypes A and B, respectively), were tested for the presence of Bartonella alsatica DNA. Two species-specific nested polymerase chain reaction assays targeting for 16S-23S rRNA intergenic spacer region and RNA polymerase β subunit genes have been developed. Forty-eight (17.20%) rabbits were infected with B. alsatica. Two-way contingency table analyses and the calculation of Cramer's V statistic showed no differences in infection rate, considering haplotype lineage or sex. The risk of infection of human population, especially for hunters in close contact with this demonstrated human pathogen, should be considered.

  19. A human model for assessing comedogenic substances.

    PubMed

    Mills, O H; Kligman, A M

    1982-11-01

    Substances that are moderately to strongly comedogenic in the rabbit ear model test have been found to be capable of inducing comedones in the human model described in this report. The test substances are applied under occlusion for one month to the upper part of the backs of young adult, black men who have large follicles. The degree of follicular hyperkeratosis is assessed by a noninvasive "follicular biopsy" techniques, employing a fast-setting cyanoacrylate glue to remove the follicular contents. The rabbit model is more sensitive than the human. Substances that are weakly comedogenic in the rabbit are probably safe for human use with the possible exception of acne-prone persons.

  20. Atorvastatin delays the glucose clearance rate in hypercholesterolemic rabbits.

    PubMed

    Cheng, Daxin; Wang, Yanli; Gao, Shoucui; Wang, Xiaojing; Sun, Wentao; Bai, Liang; Cheng, Gong; Chu, Yonglie; Zhao, Sihai; Liu, Enqi

    2015-05-01

    The administration of statin might increase the risk of new-onset diabetes in hypercholesterolemic patients based on the recent clinical evidence. However, the causal relationship must be clarified and confirmed in animal experiments. Therefore, we mimicked hypercholesterolemia by feeding rabbits a high-cholesterol diet (HCD) and performed 16 weeks of atorvastatin administration to investigate the effect of statin on glucose metabolism. The intravenous glucose tolerance test showed that plasma glucose levels in the statin-treated rabbits were consistently higher and that there was a slower rate of glucose clearance from the blood than in HCD rabbits. The incremental area under the curve for glucose in the statin-treated rabbits was also significantly larger than in the HCD rabbits. However, there was no significant difference between the two groups in the intravenous insulin tolerance test. The glucose-lowering ability of exogenous insulin was not impaired by statin treatment in hypercholesterolemic rabbits. The administration of a single dose of statin did not affect glucose metabolism in normal rabbits. The statin also significantly increased the levels of high-density lipoprotein cholesterol, alanine aminotransferase and aspartate transaminase and decreased plasma levels of total cholesterol, triglycerides and low-density lipoprotein cholesterol in the hypercholesterolemic rabbits, whereas it did not affect plasma levels of glucose and insulin. The current results showed that atorvastatin treatment resulted in a significant delay of glucose clearance in hypercholesterolemic rabbits, and this rabbit model could be suitable for studying the effects of statin on glucose metabolism.

  1. Is the rabbit ear model, in its present state, prophetic of acnegenicity?

    PubMed

    Frank, S B

    1982-03-01

    The rabbit ear model has been proposed as a useful bioassay to establish the comedogenic and acnegenic qualities of chemical compounds and finished products, pharmaceutical and cosmetic, for topical application. This review highlights the many problems in performance of the test method, the absence of correlation with experience in the human, and, consequently, the serious limitations of the conclusions that can reasonably be drawn, especially for the clinical dermatologist.

  2. Fetotoxicity and teratogenesis of SWL treatment in the rabbit.

    PubMed

    Frankenschmidt, A; Heisler, M

    1998-02-01

    The potential effects of extracorporeal application of shockwaves on an embryo or fetus were explored in an animal model. In experimental Series A, the fetuses of 30 gravid rabbits were exposed to piezoelectrically induced and sonographically guided shockwaves on Day 25 or 20 of gestation under technical conditions corresponding to extracorporeal lithotripsy in humans. Fetotoxicity was examined by abdominal section 24 hours or 9 days later, and immediate/intermediate damage was assessed (resorptions, viability, gross injuries, and microscopic lesions of the target and neighboring fetuses). In series B, the kidneys of an additional 28 gravid rabbits (including a control group) were exposed to the same shockwave treatment on Day 11 of gestation in order to investigate indirect embryotoxic effects, including teratogenic potency. One day before the expected birth, the maternal kidneys, uteri, and adjacent organs were examined for lesions, and the 156 offspring were assessed for embryolethal, embryonoxious, or teratogenic sequelae. Shockwave targeting of the cranium, thorax, abdomen, or placenta was usually lethal to the fetuses. When the uterine wall or the space between two fetuses was targeted, the fetuses suffered from superficial hematoma, as was found in the surrounding soft tissues within a radius of 1.5 cm. Fetuses outside this region were vital and free of lesions. Shockwave treatment of the maternal kidney resulted in renal petechial hemorrhage or subcapsular hematoma. However, statistically significant embryotoxic or teratogenetic effects could be demonstrated neither from maternal data (resorptions) nor from fetal findings (body measurements, vitality test, inner organs, skeletal deformities). When using a piezoelectric lithotripter with a small focus of high energy, lesions of a fetus are to be expected only when it is located in or close to the focus. It seems that embryotoxic or teratogenic sequelae do not occur when shockwaves are focused outside the

  3. Ultrastructural changes to rabbit fibrin and platelets due to aspartame.

    PubMed

    Pretorius, E; Humphries, P

    2007-01-01

    The coagulation process, including thrombin, fibrin, as well as platelets, plays an important role in hemostasis, contributing to the general well-being of humans. Fibrin formation and platelet activation are delicate processes that are under the control of many small physiological events. Any one of these many processes may be influenced or changed by external factors, including pharmaceutical or nutritional products, e.g., the sweetener aspartame (L-aspartyl-L-phenylalanine methyl ester). It is known that phenylalanine is present at position P(9) and aspartate at position P(10) of the alpha-chain of human fibrinogen, and plays an important role in the conversion of fibrinogen to fibrin by the catalyst alpha-thrombin. The authors investigate the effect of aspartame on platelet and fibrin ultrastructure, by using the rabbit animal model and the scanning electron microscope. Animals were exposed to 34 mg/kg of aspartame 26x during a 2-month period. Aspartame-exposed fibrin networks appeared denser, with a thick matted fine fiber network covering thick major fibers. Also, the platelet aggregates appeared more granular than the globular control platelet aggregates. The authors conclude by suggesting that aspartame usage may interfere with the coagulation process and might cause delayed fibrin breakup after clot formation. They suggest this, as the fibrin networks from aspartame-exposed rabbits are more complex and dense, due to the netlike appearance of the minor, thin fibers. Aspartame usage should possibly be limited by people on anti-clotting medicine or those with prone to clot formation.

  4. 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

  5. Role of Tir and Intimin in the Virulence of Rabbit Enteropathogenic Escherichia coli Serotype O103:H2

    PubMed Central

    Marchès, Olivier; Nougayrède, Jean-Philippe; Boullier, Séverine; Mainil, Jacques; Charlier, Gérard; Raymond, Isabelle; Pohl, Pierre; Boury, Michèle; De Rycke, Jean; Milon, Alain; Oswald, Eric

    2000-01-01

    Attaching and effacing (A/E) rabbit enteropathogenic Escherichia coli (REPEC) strains belonging to serogroup O103 are an important cause of diarrhea in weaned rabbits. Like human EPEC strains, they possess the locus of enterocyte effacement clustering the genes involved in the formation of the A/E lesions. In addition, pathogenic REPEC O103 strains produce an Esp-dependent but Eae (intimin)-independent alteration of the host cell cytoskeleton characterized by the formation of focal adhesion complexes and the reorganization of the actin cytoskeleton into bundles of stress fibers. To investigate the role of intimin and its translocated coreceptor (Tir) in the pathogenicity of REPEC, we have used a newly constructed isogenic tir null mutant together with a previously described eae null mutant. When human HeLa epithelial cells were infected, the tir mutant was still able to induce the formation of stress fibers as previously reported for the eae null mutant. When the rabbit epithelial cell line RK13 was used, REPEC O103 produced a classical fluorescent actin staining (FAS) effect, whereas both the eae and tir mutants were FAS negative. In a rabbit ligated ileal loop model, neither mutant was able to induce A/E lesions. In contrast to the parental strain, which intimately adhered to the enterocytes and destroyed the brush border microvilli, bacteria of both mutants were clustered in the mucus without reaching and damaging the microvilli. The role of intimin and Tir was then analyzed in vivo by oral inoculation of weaned rabbits. Although both mutants were still present in the intestinal flora of the rabbits 3 weeks after oral inoculation, neither mutant strain induced any clinical signs or significant weight loss in the inoculated rabbits whereas the parental strain caused the death of 90% of the inoculated rabbits. Nevertheless, an inflammatory infiltrate was present in the lamina propria of the rabbits infected with both mutants, with an inflammatory response greater

  6. Single dose adenovirus vectored vaccine induces a potent and long-lasting immune response against rabbit hemorrhagic disease virus after parenteral or mucosal administration.

    PubMed

    Fernández, Erlinda; Toledo, Jorge R; Chiong, Maylin; Parra, Francisco; Rodríguez, Elsa; Montero, Carlos; Méndez, Lídice; Capucci, Lorenzo; Farnós, Omar

    2011-08-15

    Rabbit hemorrhagic disease virus (RHDV) is the etiological agent of a lethal and contagious disease of rabbits that remains as a serious problem worldwide. As this virus does not replicate in cell culture systems, the capsid protein gene has been expressed in heterologous hosts or inserted in replication-competent viruses in order to obtain non-conventional RHDV vaccines. However, due to technological or safety issues, current RHDV vaccines are still prepared from organs of infected rabbits. In this work, two human type 5 derived replication-defective adenoviruses encoding the rabbit hemorrhagic disease virus VP60 capsid protein were constructed. The recombinant protein was expressed as a multimer in mouse and rabbit cell lines at levels that ranged from approximately 120 to 160 mg/L of culture. Mice intravenously or subcutaneously inoculated with a single 10(8) gene transfer units (GTU) dose of the AdVP60 vector (designed for VP60 intracellular expression) seroconverted at days 7 and 14 post-immunization, respectively. This vector generated a stronger response than that obtained with a second vector (AdVP60sec) designed for VP60 secretion. Rabbits were then immunized by parenteral or mucosal routes with a single 10(9)GTU dose of the AdVP60 and the antibody response was evaluated using a competition ELISA specific for RHDV or RHDVa. Protective hemagglutination inhibition (HI) titers were also promptly detected and IgG antibodies corresponding with inhibition percentages over 85% persisted up to one year in all rabbits, independently of the immunization route employed. These levels were similar to those elicited with inactivated RHDV or with VP60 obtained from yeast or insect cells. IgA specific antibodies were only found in saliva of rabbits immunized by intranasal instillation. The feasibility of VP60 production and vaccination of rabbits with replication-defective adenoviral vectors was demonstrated.

  7. Dwarfism and Altered Craniofacial Development in Rabbits Is Caused by a 12.1 kb Deletion at the HMGA2 Locus.

    PubMed

    Carneiro, Miguel; Hu, Dou; Archer, John; Feng, Chungang; Afonso, Sandra; Chen, Congying; Blanco-Aguiar, José A; Garreau, Hervé; Boucher, Samuel; Ferreira, Paula G; Ferrand, Nuno; Rubin, Carl-Johan; Andersson, Leif

    2017-02-01

    The dwarf phenotype characterizes the smallest of rabbit breeds and is governed largely by the effects of a single dwarfing allele with an incompletely dominant effect on growth. Dwarf rabbits typically weigh under 1 kg and have altered craniofacial morphology. The dwarf allele is recessive lethal and dwarf homozygotes die within a few days of birth. The dwarf phenotype is expressed in heterozygous individuals and rabbits from dwarf breeds homozygous for the wild-type allele are normal, although smaller when compared to other breeds. Here, we show that the dwarf allele constitutes a ∼12.1 kb deletion overlapping the promoter region and first three exons of the HMGA2 gene leading to inactivation of this gene. HMGA2 has been frequently associated with variation in body size across species. Homozygotes for null alleles are viable in mice but not in rabbits and probably not in humans. RNA-sequencing analysis of rabbit embryos showed that very few genes (4-29 genes) were differentially expressed among the three HMGA2/dwarf genotypes, suggesting that dwarfism and inviability in rabbits are caused by modest changes in gene expression. Our results show that HMGA2 is critical for normal expression of IGF2BP2, which encodes an RNA-binding protein. Finally, we report a catalog of regions of elevated genetic differentiation between dwarf and normal-size rabbits, including LCORL-NCAPG, STC2, HOXD cluster, and IGF2BP2 Levels and patterns of genetic diversity at the LCORL-NCAPG locus further suggest that small size in dwarf breeds was enhanced by crosses with wild rabbits. Overall, our results imply that small size in dwarf rabbits results from a large effect, loss-of-function (LOF) mutation in HMGA2 combined with polygenic selection.

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

    PubMed

    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

    2014-11-01

    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