Potential effect of ezetimibe against Mycobacterium tuberculosis infection in type II diabetes.

BACKGROUND AND OBJECTIVE: Tuberculosis (TB) risk might be increased in patients with diabetes by factors other than hyperglycaemia, such as dyslipidaemia. Host lipids are essential energy sources used by mycobacteria to persist in a latent TB state. A potential therapy targeting cholesterol catabolism of mycobacteria has been proposed, but the potential of cholesterol-lowering drugs as anti-TB therapy is unclear. The purpose of this study was to determine the effects of ezetimibe, a 2-azetidinone cholesterol absorption inhibitor, on intracellular mycobacteria survival and dormancy. METHODS: Intracellular mycobacteria survival was determined by measurements of ATP activity and colony-formation units (CFUs). Gene expression profiles of hypoxia-induced dormant Mycobacterium tuberculosis (Mtb) were analysed by real-time PCR. Flow cytometry and microscopy analysis were used to measure the lipid loads of human macrophages with or without ezetimibe treatment. QuantiFERON-TB Gold In-Tube (QFT-G-IT) assays were performed to diagnose latent TB infection. The levels of intracellular cholesterol/ triglyceride were measured by an enzymatic fluorometric method. RESULTS: Ezetimibe was capable of effectively lowering intracellular growth of Mtb and hypoxia-induced dormant Mtb. There was a significant decrease in Mtb growth in leucocytes from ezetimibe-treated patients with diabetes in terms of ATP levels of intracellular mycobacteria and CFU formation. Also, patients receiving ezetimibe therapy had a lower prevalence of latent TB and had lower intracellular lipid contents. CONCLUSION: Ezetimibe, which is a currently marketed drug, could hold promise as an adjunctive, host-directed therapy for TB.

Analysis of the immune response of human dendritic cells to Mycobacterium tuberculosis by quantitative proteomics.

BACKGROUND: The cellular immune response for Mycobacterium tuberculosis (M. tuberculosis) infection remained incompletely understood. To uncover membrane proteins involved in this infection mechanism, an integrated approach consisting of an organic solvent-assisted membrane protein digestion, stable-isotope dimethyl labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was used to comparatively profile the membrane protein expression of human dendritic cells upon heat-killed M. tuberculosis (HKTB) treatment. RESULTS: Organic solvent-assisted trypsin digestion coupled with stable-isotope labeling and LC-MS/MS analysis was applied to quantitatively analyze the membrane protein expression of THP-1 derived dendritic cells. We evaluated proteins that were upregulated in response to HKTB treatment, and applied STRING website database to analyze the correlations between these proteins. Of the investigated proteins, aminopeptidase N (CD13) was found to be largely expressed after HKTB treatment. By using confocal microscopy and flow cytometry, we found that membranous CD13 expression was upregulated and was capable of binding to live mycobacteria. Treatment dendritic cell with anti-CD13 antibody during M. tuberculosis infection enhanced the ability of T cell activation. CONCLUSIONS: Via proteomics data and STRING analysis, we demonstrated that the highly-expressed CD13 is also associated with proteins involved in the antigen presenting process, especially with CD1 proteins. Increasing expression of CD13 on dendritic cells while M. tuberculosis infection and enhancement of T cell activation after CD13 treated with anti-CD13 antibody indicates CD13 positively involved in the pathogenesis of M. tuberculosis.

Agenesis of right upper lobe of lung.

Agenesis of the right upper lobe of the lung is a very uncommon congenital anomaly and may be referred to chest clinics in adulthood for an incidental finding of abnormal chest radiograph. The presentations of chest radiograph may imitate many common situations such as right upper lobe collapse presenting as an ipsilateral shifting of the mediastinum or elevation of the right hemidiaphragm due to eventration or subdiaphragmatic lesions. A chest computed tomography is considered the most conclusive examination used to diagnose lung agenesis. Three-dimensional reconstructed images can be particularly helpful in delineating abnormalities of the bronchi and associated arterial and venous structures. We describe here a young woman with allergic rhinitis and bronchial asthma since her early childhood. She was referred to our clinic for an incidental finding of abnormal chest radiograph after a school health checkup. Right upper lobe atelectasis or intra-abdominal lesions were initially suspected. After a thorough image study, she was diagnosed as a case of agenesis of the right upper lobe. Our report emphasizes the importance that a high index of suspicion and adequate image investigation are necessary to diagnose congenital lung anomalies.

Intrathoracic tracheal obstruction caused by a carotid mycotic aneurysm in a patient with deep neck infection--a case report.

Upper airway obstruction secondary to a carotid mycotic aneurysm has not been previously reported. We describe a patient with a mycotic aneurysm associated with a deep neck infection and presenting with acute tracheal obstruction. Recognition of this condition is important to avoid inadvertent rupture of the aneurysm in the course of diagnostic aspiration or surgical drainage. Physical findings, including a pulsating mass and an arterial bruit, in addition to appropriate imaging studies, may be helpful in suggesting the diagnosis. In particular, both neck and chest contrast-enhanced computed tomography scans may give important clues to the presence of a vascular lesion. In a patient with an infected neck mass and tracheal compression, a common carotid mycotic aneurysm should be considered in the differential diagnosis.