60 research outputs found

    Gross pathology and hydrostatic test of lungs from infected mice with combination therapy or monotherapy.

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    <p>(A) Gross pathology of mouse lungs with combination therapy is shown. Mice intranasally inoculated with an extremely high dose (3741 MLD<sub>50</sub>) of PR8 virus were treated with laninamivir octanoate. The mice were additionally administered artificial surfactant (combination therapy, lower panels) or normal saline solution (monotherapy, upper panels) intranasally once daily during 3–14 days postinfection. Five mice in each group were sacrificed at 7 days postinfection, when the mouse survival rate in the monotherapy group was approximately 50%. Arrowheads indicate the area that appeared relatively healthy. (B) Hydrostatic lung test using mouse lungs from the monotherapy (tube number 1–5) and the combination therapy (tube number 6–10) groups is shown. The arrow indicates collapsing lungs (tube numbers 2–5). The arrowhead indicates floating lungs.</p

    Bifunctional properties and characterization of a novel sialidase with esterase activity from <i>Bifidobacterium bifidum</i>

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    <p>Sialidases catalyze the removal of terminal sialic acid from various complex carbohydrates. In the gastrointestinal tract, sialic acid is commonly found in the sugar chain of mucin, and many enteric commensals use mucin as a nutrient source. We previously identified two different sialidase genes in <i>Bifidobacterium bifidum</i>, and one was cloned and expressed as an extracellular protein designated as exo-α-sialidase SiaBb2. The other exo-α-sialidase gene (<i>siabb1)</i> from the same bifidobacterium encodes an extracellular protein (SiaBb1) consisting of 1795 amino acids with a molecular mass of 189 kDa. SiaBb1 possesses a catalytic domain that classifies this enzyme as a glycoside hydrolase family 33 member. SiaBb1 preferentially hydrolyzes α2,3-linked sialic acid over α2,6-linked sialic acid from sialoglycan, which is the same as SiaBb2. However, SiaBb1 has an SGNH hydrolase domain with sialate-<i>O</i>-acetylesterase activity and an N-terminal signal sequence and C-terminal transmembrane region. SiaBb1 is the first bifunctional sialidase identified with esterase activity.</p> <p><b>Abbreviations</b>: GalNAc: N-acetyl-D-galactosamine; Fuc: L-fucose; Gal: D-galactose</p> <p>Sialidase (SiaBb1) of <i>Bifidobacterium bifidum</i> had both activities of sialate-<i>O</i>- acetylesterase activity with SGNH hydrolase domain and hydrolysis activity with catalytic domain</p

    Survival curves and body weights of infected mice with combination therapy or monotherapy.

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    <p>(A) Survival curves of infected mice with combination therapy of artificial surfactant with laninamivir octanoate are shown. Mice infected with an extremely high dose (3741 MLD<sub>50</sub>) of PR8 virus were treated with laninamivir octanoate. The mice were additionally administered artificial surfactant (combination therapy, red line) or normal saline solution (monotherapy, blue line) intranasally once daily during 3–14 days postinfection. Significant differences in mouse survival rates between the combination therapy and monotherapy groups were analyzed by the log-rank original method. Experiments were independently repeated three times. Percentage survival in a representative experiment is shown. (B) Mouse body weight of the combination therapy (red line) and monotherapy (blue line) groups is shown. Experiments were independently repeated three times. The percentage of mouse body weight in a representative experiment is shown. Differences in means ± SD are shown.</p

    SP-D levels in infected lungs and survival of infected mice treated with artificial surfactant.

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    <p>(A) SP-D levels in lung homogenates from mice infected with the middle dose (5 MLD<sub>50</sub>) of PR8 virus were measured by ELISA. Infected mice were sacrificed at the indicated days, and then clarified lung homogenates (<i>n</i> = 5 or 6) were used. Differences in means ± SD and <i>p</i> values are shown. **<i>p</i><0.01, ***<i>p</i><0.001. (B) Survival curves of infected mice administered artificial surfactant are shown. Mice infected with a low dose (2 MLD<sub>50</sub>) of PR8 virus were additionally administered artificial surfactant (<i>n</i> = 8, red line) or normal saline solution (<i>n</i> = 8, blue line) intranasally once daily during 3–8 days postinfection. Significant differences in the survival rates of groups of mice treated with artificial surfactant or normal saline solution were analyzed by the log-rank original method. Percentage survival is shown.</p

    Blood O<sub>2</sub> and CO<sub>2</sub> pressures of infected mice with combination therapy or monotherapy.

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    <p>Mice intranasally inoculated with an extremely high dose (3741 MLD<sub>50</sub>) of PR8 virus were treated with laninamivir octanoate. The mice were additionally administered artificial surfactant (combination therapy, red lines) or normal saline solution (monotherapy, blue lines) intranasally once daily during 3–14 days postinfection. Mice (<i>n</i> = 3–6) in each group were sacrificed at the indicated days postinfection. Mice in each group were sacrificed at 7 days postinfection, when the mouse survival rate in the monotherapy group was approximately 50%. Blood was collected and immediately measured for O<sub>2</sub> (left panel) and CO<sub>2</sub> (right panel) pressures using the i-STAT portable blood gas analyzer. Differences in means ± SD and <i>p</i> values are shown. *<i>p</i><0.05.</p

    Cytokine and chemokine expression in lungs from infected mice with combination therapy or monotherapy.

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    <p>Mice intranasally inoculated with an extremely high dose (3741 MLD<sub>50</sub>) of PR8 virus were treated with laninamivir octanoate. The mice were additionally administered artificial surfactant (combination therapy, red bars) or normal saline solution (monotherapy, blue bars) intranasally once daily during 3–14 days postinfection. Three mice from each group were sacrificed at the indicated days postinfection and their lung homogenates were used to analyze the expression of 22 cytokines and chemokines using the MILLIPLEX MAP Panel. Only 12 cytokines and chemokines are shown; the remainder was under the limit of detection for the assay. The concentration in each panel is pg/ml. Differences in means ± SD are shown.</p
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