Development and validation of large animal models of Pseudomonas aeruginosa ventilator-associated pneumonia is needed for testing new drug candidates in a manner mimicking how they will be used clinically. We have developed a new model in which rabbits were ventilated with low-tidal volume and challenged with P. aeruginosa to recapitulate hallmark clinical features of acute respiratory distress syndrome (ARDS): acute lung injury and inflammation, progressive decrease in arterial oxygen partial pressure to fractional inspired oxygen PaO2:FiO2, leukopenia, neutropenia, thrombocytopenia, hyperlactatemia, severe hypotension, bacterial dissemination from lung to other organs, multiorgan dysfunction, and ultimately death. We evaluated the predictive power of this rabbit model for antibiotic efficacy testing by determining whether a humanized dosing regimen of meropenem, a potent antipseudomonal β-lactam antibiotic, when administered with or without intensive care unit (ICU)-supportive care (fluid challenge and norepinephrine), could halt or reverse natural disease progression. Our humanized meropenem dosing regimen produced plasma concentration-time profile in the rabbit model similar to those reported in patients with ventilator-associated bacterial pneumonia. In this rabbit model, treatment with humanized meropenem and ICU-supportive care achieved the highest level of survival, halted the worsening of ARDS biomarkers and reversed lethal hypotension, although treatment with humanized meropenem alone also conferred some protection when compared to treatment with placebo (saline) alone or placebo plus ICU-supportive care. In conclusion, this rabbit model could help predict whether an antibiotic will be efficacious for the treatment of human ventilator-associated pneumonia.
This study aimed to screen the anticancer and antioxidant potential and antimicrobial activity of methanol, petroleum ether, chloroform, ethyl acetate, butanol of Euphorbia hirta Linn. extracts (EH-Me, EH-PE, EH-Ch, EH-EA and EH-Bu, respectively). The results of 2,2-diphenyl-1-pycrylhydrazyl (DPPH) radical scavenging assay and lipid peroxidation inhibition assay showed that EH-EA was the strongest antioxidant (IC50 = 10.33 ± 0.01 µg/mL; IC50 = 1.48 ± 0.12 µg/mL, respectively) compared to all other extracts. In the antimicrobial activity of the extracts against eight strains of Gram-positive and Gram-negative bacteria using the agar disc diffusion method, we found the EH-EA to be the best antimicrobial agent. Anticancer activities of those extracts were examined by sulforhodamine B (SRB) in vitro cytotoxicity assay on two cancer cell lines, including lung cancer cells NCI-H460 and liver cancer cells Hep G2. EH-EA at concentration of 100 μg/mL has significant inhibitory activity the growth of lung cancer cells NCI-H460 and liver cancer cells Hep G2 compared to all other extracts. Our results suggest that E. hirta Linn. extracts possess significant biological activities, including antimicrobial, antioxidant, and moderate anticancer properties. Our results show that this plant could be a good source for natural antioxidants and a possible pharmaceutical supplement. Among five analyzed extracts, EH-EA extract has the strongest activities, and should be used to determine phytochemicals and mechanisms of these activities.
From an EtOAc-soluble fraction of the leaves of Azadirachta indica, two new 28-norlimonoids named nimbandiolactone-21 (1) and nimbandioloxyfuran (2), together with nimbandiolactone-23 (3), were isolated. Their relative structures were elucidated based on NMR spectroscopic interpretation and biosynthetic consideration. Nimbandioloxyfuran (2) and nimbandiolactone-23 (3) showed potent α-glucosidase inhibitory activity, with the IC values of 46.2 and 38.7 μM, respectively.
Abstract-DICOM specifies that digital data values should be linearly mapped to just-noticable differences (JNDs) in luminance. Increasing the number of JNDs available requires increasing the display's dynamic range. However, operating over too wide a range may cause human observers to miss contrast in dark regions due to adaptation to bright areas or, alternatively, miss edges in bright regions due to scattering in the eye. Dolby Inc.'s high dynamic range (HDR) LCD display has a maximum luminance over 2000 cd/m 2 ; bright enough to produce significant in-eye scatter. The display combines a spatially variable backlight producing a low-resolution 8-bit "backlight image" with a high-resolution 8-bit LCD panel, approximating a 16-bit greyscale display. Alternatively, by holding the backlight constant at 800 cd/m 2 , a standard medical LCD display can be simulated.We used two-alternative forced choice (2AFC) signal-detection experiments to quantify display quality. We explored whether the full-power HDR display's optical characteristics (scattering and low resolution backlight) have a negative effect on signal detection in medical images compared with a standard LCD. We used 8-bit test images derived from high-field MRI data combined with synthetic targets and synthetic Rician noise.We suggest signal detection performance with the HDR display is comparable to a standard medical LCD.Index Terms-High dynamic range, high luminicense, medical studies, user studies.
Plant growth promoting rhizobacteria (PGPR) are free-living soil bacteria (rhizosphere bacteria), rhizoplane bacteria or endophytic bacteria that may promote plant growth and suppress plant diseases. The aim of this study is to evaluate effects of 2 rhizobacteria strains belonging to the genus Pseudomonas isolated from maize rhizosphere on the plant growth promotion. The in vitro tests showed that both of strain could fix nitrogen, solubilize phosphate, produced phytohormones (IAA and GAs), and improved the germination and growth of Arabidopsis thaliana. Under the greenhouse condition, growth parameters of bacteria inoculated maizes (fresh weight of shoot, dry weight of root, chlorophyll content) were also increased significantly than those of uninoculated ones. Our results reported 2 promising bacteria strain candidates and revealed their potential as a biological agent for eco-friendly agricultural practices.
From an EtOAc-soluble fraction of the leaves of Azadirachta indica, one new lactam 28-norlimonoid named nimbandiolactam-21 (1), together with 2 known limonoids (2 and 3) were isolated. Their relative structures were elucidated based on NMR spectroscopic analysis. Nimbandiolactone-23 (2) showed the most potent α-glucosidase inhibitory activity, with an IC value of 38.7 μM. Compound 1 represents the first naturally occurring example of a 28-norlimonoid having the lactam moiety. The plausible biosynthetic pathway for the formation of lactam moiety in 1 was proposed.
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