scholarly journals Achieving Consistent Multiple Daily Low-Dose Bacillus anthracis Spore Inhalation Exposures in the Rabbit Model

2012 ◽  
Vol 2 ◽  
Author(s):  
Roy E. Barnewall ◽  
Jason E. Comer ◽  
Brian D. Miller ◽  
Bradford W. Gutting ◽  
Daniel N. Wolfe ◽  
...  
Keyword(s):  
Bacillus Anthracis ◽  
Low Dose ◽  
Rabbit Model

scholarly journals Physiological Responses to a Single Low-Dose of Bacillus anthracis Spores in the Rabbit Model of Inhalational Anthrax

Pathogens ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 461 ◽  
Author(s):  
Sarah C. Taft ◽  
Tonya L. Nichols ◽  
Stephanie A. Hines ◽  
Roy E. Barnewall ◽  
Gregory V. Stark ◽  
...  
Keyword(s):  
Bacillus Anthracis ◽  
Low Dose ◽  
Physiological Responses ◽  
Rabbit Model ◽  
Systemic Infection ◽  
Time To Death ◽  
Colony Forming Units ◽  
New Zealand White Rabbits ◽  
Bacillus Anthracis Spores ◽  
Dose Dependent

Credible dose–response relationships are needed to more accurately assess the risk posed by exposure to low-level Bacillus anthracis contamination during or following a release. To begin to fill this knowledge gap, New Zealand White rabbits were implanted with D70-PCT telemetry transmitters and subsequently aerosol challenged with average inhaled doses of 2.86 × 102 to 2.75 × 105 colony forming units (CFU) of B. anthracis spores. Rabbits exposed to a single inhaled dose at or above 2.54 × 104 CFU succumbed with dose-dependent time to death. Death was associated with increases above baseline in heart rate, respiration rate, and body temperature and all rabbits that died exhibited bacteremia at some point prior to death. Rabbits that inhaled doses of 2.06 × 103 CFU or lower survived to the end of the study and showed no or minimal adverse changes in the measured physiological responses in response to the challenge. Moreover, no bacteremia nor toxemia were observed in rabbits that survived to the end of the study. Overall, the data indicate that challenge doses of B. anthracis below the level sufficient to establish systemic infection do not produce observable physiological responses; however, doses that triggered a response resulted in death.

scholarly journals Physiological Responses to Multiple Low-Doses of Bacillus anthracis Spores in the Rabbit Model of Inhalation Anthrax

Pathogens ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 877
Author(s):  
Sarah C. Taft ◽  
Tonya L. Nichols ◽  
Stephanie A. Hines ◽  
Roy E. Barnewall ◽  
Gregory V. Stark ◽  
...  
Keyword(s):  
Body Temperature ◽  
Bacillus Anthracis ◽  
Low Dose ◽  
Rabbit Model ◽  
Clinical Signs ◽  
Low Doses ◽  
Inhalation Anthrax ◽  
Daily Dose ◽  
Bacillus Anthracis Spores ◽  
Accumulated Dose

Bacillus anthracis spores that are re-aerosolized from surface deposits after initial contamination present significant health risks for personnel involved in decontamination. To model repeated exposure to low dose B. anthracis spores, three groups of seven rabbits were challenged with multiple low-doses of B. anthracis spores 5 days a week for 3 weeks. Mortality, body temperature, heart and respiration rates, hematology, C-reactive protein, bacteremia, and serum protective antigen were monitored for 21 days post-exposure after the last of multiple doses. All rabbits exposed to a mean daily dose of 2.91 × 102 colony forming units (CFU) survived and showed minimal physiological changes attributable to exposure. One of seven rabbits receiving a mean daily dose of 1.22 × 103 CFU died and four of seven receiving a mean daily dose of 1.17 × 104 CFU died. The LD50 was calculated to be 8.1 × 103 CFU of accumulated dose. Rabbits that succumbed to the higher dose exhibited bacteremia and increases above baseline in heart rate, respiration rate, and body temperature. Two rabbits in the mean daily dose group of 1.17 × 104 CFU exhibited clinical signs of inhalation anthrax yet survived. This study provides a description of lethality, pathophysiology, and pathology in a controlled multiple low-dose inhalation exposure study of B. anthracis in the rabbit model. The data suggest that the accumulated dose is important in survival outcome and that a subset of rabbits may show clinical signs of disease but fully recover without therapeutic intervention

scholarly journals Mechanism of catheter thrombosis: comparison of the antithrombotic activities of fondaparinux, enoxaparin, and heparin in vitro and in vivo

Blood ◽  
2011 ◽  
Vol 118 (25) ◽  
pp. 6667-6674 ◽  
Author(s):  
Jonathan W. Yau ◽  
Alan R. Stafford ◽  
Peng Liao ◽  
James C. Fredenburgh ◽  
Robin Roberts ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Low Dose ◽  
Rabbit Model ◽  
Coronary Intervention ◽  
Factor Xii ◽  
Catheter Occlusion ◽  
Dose Heparin ◽  
Percutaneous Coronary ◽  
Low Dose Heparin

Abstract In patients undergoing percutaneous coronary intervention, catheter thrombosis is more frequent with fondaparinux than heparin. This study was undertaken to identify the responsible mechanism and to develop strategies for its prevention. Percutaneous coronary intervention catheter segments shortened plasma clotting times from 971 ± 92 to 352 ± 22 seconds. This activity is factor XII (fXII) dependent because it was attenuated with corn trypsin inhibitor and was abolished in fXII-deficient plasma. Heparin and enoxaparin blocked catheter-induced clotting at 0.5 and 2 anti-Xa U/mL, respectively, whereas fondaparinux had no effect. Addition of fondaparinux to bivalirudin or low-dose heparin attenuated catheter-induced clotting more than either agent alone. In a rabbit model of catheter thrombosis, a 70 anti-Xa U/kg intravenous bolus of heparin or enoxaparin prolonged the time to catheter occlusion by 4.6- and 2.5-fold, respectively, compared with saline, whereas the same dose of fondaparinux had no effect. Although 15 anti-Xa U/kg heparin had no effect on its own, when given in conjunction with 70 anti-Xa U/kg fondaparinux, the time to catheter occlusion was prolonged 2.9-fold. These findings indicate that (1) catheters are prothrombotic because they trigger fXII activation, and (2) fondaparinux does not prevent catheter-induced clotting unless supplemented with low-dose heparin or bivalirudin.

scholarly journals Human Monoclonal Antibody AVP-21D9 to Protective Antigen Reduces Dissemination of the Bacillus anthracis Ames Strain from the Lungs in a Rabbit Model

2007 ◽  
Vol 75 (7) ◽  
pp. 3414-3424 ◽  
Author(s):  
Johnny W. Peterson ◽  
Jason E. Comer ◽  
Wallace B. Baze ◽  
David M. Noffsinger ◽  
Autumn Wenglikowski ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Bacillus Anthracis ◽  
Protective Antigen ◽  
Human Monoclonal Antibody ◽  
Rabbit Model ◽  
Concomitant Treatment ◽  
Dependent Manner ◽  
Lethal Challenge ◽  
Tissue Sections ◽  
Inhalation Anthrax

ABSTRACT Dutch-belted and New Zealand White rabbits were passively immunized with AVP-21D9, a human monoclonal antibody to protective antigen (PA), at the time of Bacillus anthracis spore challenge using either nasal instillation or aerosol challenge techniques. AVP-21D9 (10 mg/kg) completely protected both rabbit strains against lethal infection with Bacillus anthracis Ames spores, regardless of the inoculation method. Further, all but one of the passively immunized animals (23/24) were completely resistant to rechallenge with spores by either respiratory challenge method at 5 weeks after primary challenge. Analysis of the sera at 5 weeks after primary challenge showed that residual human anti-PA levels decreased by 85 to 95%, but low titers of rabbit-specific anti-PA titers were also measured. Both sources of anti-PA could have contributed to protection from rechallenge. In a subsequent study, bacteriological and histopathology analyses revealed that B. anthracis disseminated to the bloodstream in some naïve animals as early as 24 h postchallenge and increased in frequency with time. AVP-21D9 significantly reduced the dissemination of the bacteria to the bloodstream and to various organs following infection. Examination of tissue sections from infected control animals, stained with hematoxylin-eosin and the Gram stain, showed edema and/or hemorrhage in the lungs and the presence of bacteria in mediastinal lymph nodes, with necrosis and inflammation. Tissue sections from infected rabbits dosed with AVP-21D9 appeared comparable to corresponding tissues from uninfected animals despite lethal challenge with B. anthracis Ames spores. Concomitant treatment with AVP-21D9 at the time of challenge conferred complete protection in the rabbit inhalation anthrax model. Early treatment increased the efficacy progressively and in a dose-dependent manner. Thus, AVP-21D9 could offer an adjunct or alternative clinical treatment regimen against inhalation anthrax.

scholarly journals Effects of Low-Dose Microwave on Healing of Fractures with Titanium Alloy Internal Fixation: An Experimental Study in a Rabbit Model

PLoS ONE ◽  
2013 ◽  
Vol 8 (9) ◽  
pp. e75756 ◽  
Author(s):  
Dongmei Ye ◽  
Yiming Xu ◽  
Han Zhang ◽  
Tengfei Fu ◽  
Lan Jiang ◽  
...  
Keyword(s):  
Experimental Study ◽  
Titanium Alloy ◽  
Internal Fixation ◽  
Low Dose ◽  
Rabbit Model

scholarly journals In Vitro and Ex Vivo Activities of Minocycline and EDTA against Microorganisms Embedded in Biofilm on Catheter Surfaces

2003 ◽  
Vol 47 (11) ◽  
pp. 3580-3585 ◽  
Author(s):  
Issam Raad ◽  
Ioannis Chatzinikolaou ◽  
Gassan Chaiban ◽  
Hend Hanna ◽  
Ray Hachem ◽  
...  
Keyword(s):  
Low Dose ◽  
Ex Vivo ◽  
Bacterial Colonization ◽  
Rabbit Model ◽  
Confocal Laser ◽  
High Dose ◽  
High Concentration ◽  
Ex Vivo Model ◽  
Highly Active

ABSTRACT Minocycline-EDTA (M-EDTA) flush solution has been shown to prevent catheter-related infection and colonization in a rabbit model and in hemodialysis patients. We undertook this study in order to determine the activities of M-EDTA against organisms embedded in fresh biofilm (in vitro) and mature biofilm (ex vivo). For the experiment with the in vitro model, a modified Robbin’s device (MRD) was used whereby 25 catheter segments were flushed for 18 h with 106 CFU of biofilm-producing Staphylococcus epidermidis, Staphyloccocus aureus, and Candida albicans per ml. Subsequently, each of the catheter segments was incubated in one of the following solutions: (i) streptokinase, (ii) heparin, (iii) broth alone, (iv) vancomycin, (v) vancomycin-heparin, (vi) EDTA, (vii) minocycline (high-dose alternating with low-dose), or (viii) M-EDTA (low-dose minocycline alternating with high-dose minocycline were used to study the additive and synergistic activities of M-EDTA). All segments were cultured quantitatively by scrape sonication. For the experiment with the ex vivo model, 54 catheter tip segments removed from patients and colonized with bacterial organisms by roll plate were longitudinally cut into two equal segments and exposed to either saline, heparin, EDTA, or M-EDTA (with high-dose minocycline). Subsequently, all segments were examined by confocal laser electron microscopy. In the in vitro MRD model, M-EDTA (with a low concentration of minocycline) was significantly more effective than any other agent in reducing colonization of S. epidermidis, S. aureus, and C. albicans (P < 0.01). M-EDTA (with a high concentration of minocycline) eradicated all staphylococcal and C. albicans organisms embedded in the biofilm. In the ex vivo model, M-EDTA (with a high concentration of minocycline) reduced bacterial colonization more frequently than EDTA or heparin (P < 0.01). We concluded that M-EDTA is highly active in eradicating microorganisms embedded in fresh and mature biofilm adhering to catheter surfaces.

Effect of repeated administration of low-dose silver nitrate for pleurodesis in a rabbit model

Respirology ◽  
2011 ◽  
Vol 16 (7) ◽  
pp. 1070-1075 ◽  
Author(s):  
ALAIN TREMBLAY ◽  
DAVID R. STATHER ◽  
MARGARET M. KELLY
Keyword(s):  
Silver Nitrate ◽  
Low Dose ◽  
Rabbit Model ◽  
Repeated Administration

22. Low Dose Nicotine Exposure Improves Posterior Spinal Fusion in an In Vivo Rabbit Model

2009 ◽  
Vol 9 (10) ◽  
pp. 12S
Author(s):  
John France ◽  
Scott Daffner ◽  
Chad Smalley ◽  
Stacey Waugh ◽  
Timothy Norman ◽  
...  
Keyword(s):  
Spinal Fusion ◽  
Low Dose ◽  
Rabbit Model ◽  
Posterior Spinal Fusion ◽  
Nicotine Exposure
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