| Anthrax lethal and edema toxins produce different patterns of cardiovascular and renal dysfunction and synergistically decrease survival in canines. | |
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MedLine Citation:
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PMID: 21067373 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: High mortality in the 2001 US and recent European anthrax outbreaks suggests that better understanding of the effects of the toxins produced by this bacterium is needed to improve treatment. METHODS AND RESULTS: Here, 24-h edema (ETx) and lethal (LeTx) toxin infusions were investigated for 96 hin sedated canines receiving mechanical ventilation. The initial study compared similarly lethal doses of ETx (n=8) or LeTx (n=15) alone. ETx was 24 times less lethal than LeTx, and the median time to death in nonsurvivors (n=6 and n=9, respectively) was shorter with ETx (42 vs 67 h; P=.04). Compared with controls(n=9), both toxins decreased arterial and central venous pressures and systemic vascular resistance and increased heart rate, cardiac index, blood urea nitrogen (BUN) level, creatinine (Cr) concentration, BUN:Cr ratio, and hepatic transaminase levels (P ≤ .05 for toxin effect or time interaction). However, ETx stimulated early diuresis,reduced serum sodium levels, and had more pronounced vasodilatory effects, compared with LeTx, as reflected by greater or earlier central venous pressures, systemic vascular resistance, and changes in the BUN:Cr ratio(P ≤ .01). LeTx progressively decreased the left ventricular ejection fraction (P ≤ .002). In a subsequent study, a lethal dose of LeTx with an equimolar nonlethal ETx dose (n=8) increased mortality, compared with LeTx alone (n=8; P= .05). CONCLUSION: Shock with ETx or LeTx may require differing supportive therapies, whereas toxin antagonists should likely target both toxins. |
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Authors:
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Daniel A Sweeney; Xizhong Cui; Steven B Solomon; David A Vitberg; Thi S Migone; Dara Scher; Robert L Danner; Charles Natanson; G Mani Subramanian; Peter Q Eichacker |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, P.H.S. Date: 2010-11-10 |
Journal Detail:
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Title: The Journal of infectious diseases Volume: 202 ISSN: 1537-6613 ISO Abbreviation: J. Infect. Dis. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-18 Completed Date: 2010-12-13 Revised Date: 2013-03-28 |
Medline Journal Info:
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Nlm Unique ID: 0413675 Medline TA: J Infect Dis Country: United States |
Other Details:
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Languages: eng Pagination: 1885-96 Citation Subset: AIM; IM |
Affiliation:
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Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antigens, Bacterial / toxicity* Bacterial Toxins / toxicity* Blood Pressure / drug effects Cardiovascular System / drug effects* Creatinine / blood Disease Models, Animal Dogs Heart Rate / drug effects Kidney / drug effects* Poisoning / pathology*, physiopathology* Survival Analysis* Transaminases / blood Urea / blood Vascular Resistance / drug effects |
| Grant Support | |
ID/Acronym/Agency:
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Z01 CL008090-02/CL/CLC NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antigens, Bacterial; 0/Bacterial Toxins; 0/anthrax toxin; 57-13-6/Urea; 60-27-5/Creatinine; EC 2.6.1.-/Transaminases |
| Comments/Corrections | |
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