Characterization of a murine model of monocrotaline pyrrole-induced acute lung injury

<p>Abstract</p> <p>Background</p> <p>New animal models of chronic pulmonary hypertension in mice are needed. The injection of monocrotaline is an established model of pulmonary hypertension in rats. The aim of this study was to establish a murine model of pulmonary hypertension by injection of the active metabolite, monocrotaline pyrrole.</p> <p>Methods</p> <p>Survival studies, computed tomographic scanning, histology, bronchoalveolar lavage were performed, and arterial blood gases and hemodynamics were measured in animals which received an intravenous injection of different doses of monocrotaline pyrrole.</p> <p>Results</p> <p>Monocrotaline pyrrole induced pulmonary hypertension in Sprague Dawley rats. When injected into mice, monocrotaline pyrrole induced dose-dependant mortality in C57Bl6/N and BALB/c mice (dose range 6–15 mg/kg bodyweight). At a dose of 10 mg/kg bodyweight, mice developed a typical early-phase acute lung injury, characterized by lung edema, neutrophil influx, hypoxemia and reduced lung compliance. In the late phase, monocrotaline pyrrole injection resulted in limited lung fibrosis and no obvious pulmonary hypertension.</p> <p>Conclusion</p> <p>Monocrotaline and monocrotaline pyrrole pneumotoxicity substantially differs between the animal species.</p

Evaluation of Angiogenesis Using Micro-Computed Tomography in a Xenograft Mouse Model of Lung Cancer

Quantitative evaluation of lung tumor angiogenesis using immunohistochemical techniques has been limited by difficulties in generating reproducible data. To analyze intrapulmonary tumor angiogenesis, we used high-resolution micro-computed tomography (micro-CT) of lung tumors of mice inoculated with mouse Lewis lung carcinoma (LLC1) or human adenocarcinoma (A549) cell lines. The lung vasculature was filled with the radiopaque silicone rubber, Microfil, through the jugular vein (in vivo application) or pulmonary artery (ex vivo application). In addition, human adenocarcinoma lung tumor-bearing mice treated site-specifically with humanized monoclonal antibody (bevacizumab) against vascular endothelial growth factor. Quantitative analysis of lung tumor microvessels imaged with micro-CT showed that more vessels (mainly small, <0.02 mm2) were filled using the in vivo (5.4%) compared with the ex vivo (2.1%) method. Furthermore, bevacizumab-treated lung tumor-bearing mice showed significantly reduced lung tumor volume and lung tumor angiogenesis compared with untreated mice as assessed by micro-CT. Interestingly, microvascularization of mainly the smaller vessels (<0.02 mm2) was reduced after bevacizumab treatment. This observation with micro-CT was nicely correlated with immunohistochemical measurement of microvessels. Therefore, micro-CT is a novel method for investigating lung tumor angiogenesis, and this might be considered as an additional complementary tool for precise quantification of angiogenesis

Potential Applications of Flat-Panel Volumetric CT in Morphologic and Functional Small Animal Imaging

Noninvasive radiologic imaging has recently gained considerable interest in basic and preclinical research for monitoring disease progression and therapeutic efficacy. In this report, we introduce flat-panel volumetric computed tomography (fpVCT) as a powerful new tool for noninvasive imaging of different organ systems in preclinical research. The three-dimensional visualization that is achieved by isotropic high-resolution datasets is illustrated for the skeleton, chest, abdominal organs, and brain of mice. The high image quality of chest scans enables the visualization of small lung nodules in an orthotopic lung cancer model and the reliable imaging of therapy side effects such as lung fibrosis. Using contrast-enhanced scans, fpVCT displayed the vascular trees of the brain, liver, and kidney down to the subsegmental level. Functional application of fpVCT in dynamic contrast-enhanced scans of the rat brain delivered physiologically reliable data of perfusion and tissue blood volume. Beyond scanning of small animal models as demonstrated here, fpVCT provides the ability to image animals up to the size of primates

SPINK5 and netherton syndrome: Novel mutations, demonstration of missing LEKTI, and differential expression of transglutaminases

10.1111/j.0022-202X.2004.23220.xJournal of Investigative Dermatology1233474-483JIDE