Mitochondrial dynamics modulate the allergic inflammation in a murine model of allergic rhinitis.

OBJECTIVE: Allergic rhinitis (AR) is a common allergic disorder, afflicting thousands of human beings. Aberrant mitochondrial dynamics are important pathological elements for various immune cell dysfunctions and allergic diseases. However, the connection between mitochondrial dynamics and AR remains poorly understood. This study aimed to determine whether mitochondrial dynamics influence the inflammatory response in AR. METHODS: In the present study, we established a murine model of AR by sensitization with ovalbumin (OVA). Then, we investigated the mitochondrial morphology in mice with AR by transmission electron microscopy and confocal fluorescence microscopy, and evaluated the role of Mdivi-1 (an inhibitor of mitochondrial fission) on allergic symptoms, inflammatory responses, allergic-related signals, and reactive oxygen species formation. RESULTS: There was a notable enhancement in mitochondrial fragmentation in the nasal mucosa of mice following OVA stimulation, whereas Mdivi-1 prevented aberrant mitochondrial morphology. Indeed, Mdivi-1 alleviated the rubbing and sneezing responses in OVA-sensitized mice. Compared with vehicle-treated ones, mice treated with Mdivi-1 exhibited a reduction in interleukin (IL)-4, IL-5, and specific IgE levels in both serum and nasal lavage fluid, and shown an amelioration in inflammatory response of nasal mucosa. Meanwhile, Mdivi-1 treatment was associated with a suppression in JAK2 and STAT6 activation and reactive oxygen species generation, which act as important signaling for allergic response. CONCLUSION: Our findings reveal mitochondrial dynamics modulate the allergic responses in AR. Mitochondrial dynamics may represent a promising target for the treatment of AR.

[FDG dual-head tomography with coincidence imaging and serum tumor marker assays for the assessment of malignancy of pulmonary lesions].

OBJECTIVE: To evaluate the performance of FDG dual-head tomography with coincidence (DHTC) imaging and serum tumor marker assays in identifying lung carcinoma in 160 patients with abnormal findings on chest radiography. METHODS: A prospective evaluation of FDG imaging with DHTC and the measurement of 3 serum tumor markers for lung cancer (carcinoembryonic antigen, CYFRA21-1 and neuron specific enolase) were performed in two weeks in 160 consecutive patients with known or suspected lung malignancy. All images were analyzed visually, and the count ratio of tumor to normal tissue (T/N ratio) was calculated. It was considered positive if the FDG uptake was increased relative to that in the adjacent lung tissue, and the uptake was focal and the T/N ratio > or = 1.3. The serum tumor marker test was considered positive for malignancy if the serum level of at least 1 marker was elevated. RESULTS: 127 patients were proven to have lung cancer by pathology, and 33 patients had benign lung disease. The sensitivity, specificity and accuracy of FDG DHTC in assessing lung cancer were 94.5%, 84.8% and 92.5%, respectively, and those of the serum tumor markers were 67.7%, 84.8% and 71.3%, respectively. FDG DHTC showed significantly higher sensitivity (P < 0.001) and accuracy (P < 0.001) than serum tumor markers. Four patients with lung cancer had negative findings on FDG DHTC but had positive serum markers. CONCLUSION: FDG DHTC imaging is a powerful tool for evaluating patients with lung lesions suggestive of malignancy. Although the determination of serum tumor marker levels is less accurate than FDG DHTC, the combination of a positive FDG result and positive tumor markers may be helpful in improving the diagnosis of lung cancer.