13 research outputs found
Elevated Carbon Monoxide to Carbon Dioxide Ratio in the Exhaled Breath of Mice Treated With a Single Dose of Lipopolysaccharide
BACKGROUND: Analysis of volatile organic chemicals in breath holds promise for noninvasive diagnosis and monitoring of patients, but investigation of this in experimental mouse models has been limited. Of particular interest is endogenous production of carbon monoxide as a biomarker of inflammation and, more particularly, during sepsis.
METHODS: Using a nose-only collection procedure for unanesthetized individual adult mice and sensitive gas chromatography of carbon monoxide (CO) and carbon dioxide (CO2) of sampled breath, we investigated the responses of mice to one-time injections with different doses of purified Escherichia coli lipopolysaccharide. Two strains of mice were examined: BALB/c and C3H, including an endotoxin-resistant mutant (HeJ) as well as the wild type (HOuJ).
RESULTS: The CO to CO2 ratio increased in a dose-responsive manner within hours in treated BALC/c mice but not control mice. The CO/CO2 values declined to the range of control mice within 48-72 h after the injection of lipopolysaccharide. Breath CO/CO2 values correlated with systemic inflammation biomarkers in serum and heme oxygenase-1 gene expression in blood. C3H/HOuJ mice, but not the HeJ mice, had similar increases of the CO/CO2 ratio in response to the endotoxin.
CONCLUSIONS: Carbon monoxide concentrations in exhaled breath of at least 2 strains of mice increase in response to single injections of endotoxin. The magnitude of increase was similar to what was observed with a bacteremia model. These findings with an experimental model provide a rationale for further studies of normalized CO concentrations in human breath as an informative biomarker for staging and monitoring of sepsis
Elevated Carbon Monoxide to Carbon Dioxide Ratio in the Exhaled Breath of Mice Treated With a Single Dose of Lipopolysaccharide
Elevated Carbon Monoxide in the Exhaled Breath of Mice during a Systemic Bacterial Infection
Pathogen and Host Response Dynamics in a Mouse Model of Borrelia hermsii Relapsing Fever
Scatter plot of normalized CO (CO/CO<sub>2</sub>) in breath samples on serum heme oxygenase-1 concentrations in 6 uninfected, 7 infected, and 5 treated male SCID mice at the time of euthanasia, as described in text and in Figure 5 legend.
<p>The least-squares linear regression line and the coefficient of determination (<i>R<sup>2</sup></i>) are shown.</p
Daily normalized CO concentrations (CO/CO<sub>2</sub>) in the exhaled breath samples from 18 individual adult male SCID mice by state of infection (uninfected, infected, or treated) on day of study.
<p><i>B. hermsii</i> infection was initiated on day 0 in 12 mice. On day 4 after the breath sampling, 5 infected mice were euthanized, 2 mice remained infected until euthanasia the next day, and 5 mice began treatment with the antibiotic ceftriaxone. Two uninfected mice were euthanized after day 5′s collection, and there is missing data for 1 treated mouse on day 9. The course for each mouse is given in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0069802#pone.0069802.s002" target="_blank">Figure S2</a> of SI. Inset, box-whisker plots of CO/CO<sub>2</sub> values for 6 uninfected mice, which were all sampled on days 4 and 5, and 12 untreated infected mice, 10 of which were sampled on day 4 only and 2 of which were sampled on day 5 as well.</p
Box-whisker plots of normalized CO concentrations (CO/CO<sub>2</sub>) in the exhaled breath samples from 8 groups of 3 SCID mice infected with <i>B. </i> by day of infection.
<p>Breathhermsii samples were collected for 3 days before infection after the sampling on day 0. Inset, CO/CO<sub>2</sub> by sex of group.</p
Selected acute phase reactants, cytokines, and other inflammation biomarkers in the plasma of BALB/c<i>-scid</i> mice that were uninfected (n = 6) or infected (n = 12) with <i>Borrelia hermsii</i>.
<p>Samples were obtained when bacteremia reached its peak in infected mice; analyte concentrations in wt per ml were determined by immunoassay as described in text. The graphs are box-whisker plots of log<sub>10</sub>-transformed values. Each box indicates the first and third quartiles, and the line inside the box is the median. The 1.5× interquartile range is indicated by the vertical line (whiskers) bisecting the box, and values outside this range are indicated by asterisks. If the result for a biomarker was “undetected”, we report the lower limit of quantitation for that substance on the run as the concentration for that specimen. Abbreviations: IL, Interleukin; VCAM1, Vascular Cell Adhesion Molecule-1.</p
Assembled apparatus for collection of exhaled breath samples from groups or individual mice.
<p>Selected components of the apparatus are indicated.</p
Least-squares linear regressions of carbon monoxide (CO) in parts per billion volume (ppbv) on total carbon dioxide (CO<sub>2</sub>) in % for samples of collected breath from mice infected with <i>B. hermsii</i> and uninfected controls in two experiments.
<p>Coefficients of determination (<i>R<sup>2</sup></i>) for each group are shown in the figures. Upper panel: Eight groups of 3 BALB/c-<i>scid</i> male and female mice sampled on days −4, −2, and 0 (uninfected; total of 24 determinations) and injected with <i>B. hermsii</i> on day 0 after sampling. Mice were sampled again in the same groups on days 3 and 5. The plot shows the day 5 values for 8 groups of mice (infected). The inset indicates the symbols for status of infection. The regression coefficients (95% confidence interval) for the combined data for days 4 and 5 were 57 (39–75) for uninfected mice (<i>F</i><sub>1,22</sub> = 43.2; <i>p</i><10<sup>−4</sup>) and 175 (97–253) for infected mice (<i>F</i><sub>1,6</sub> = 30.4; <i>p</i> = 0.002). Lower panel: Six groups of 3 C.B-17-<i>scid</i> male mice infected on day 0 and 5 groups of 3 uninfeceted mice sampled on days 4 and 5. The inset indicates the symbols for status of infection and day of sampling. The regression coefficients for the combined data for days 4 and 5 were 30 (10–51) for uninfected mice (<i>F</i><sub>1,10</sub> = 11.3; <i>p</i> = 0.007) and 195 (131–259) for infected mice (<i>F</i><sub>1,10</sub> = 43.2; <i>p</i><10<sup>−4</sup>).</p
