Flavonone treatment reverses airway inflammation and remodelling in an asthma murine model

Background and Purpose

Asthma is an inflammatory disease that involves airway hyperresponsiveness and remodelling. Flavonoids have been associated to anti-inflammatory and antioxidant activities and may represent a potential therapeutic treatment of asthma. Our aim was to evaluate the effects of the sakuranetin treatment in several aspects of experimental asthma model in mice.

Experimental Approach

Male BALB/c mice received ovalbumin (i.p.) on days 0 and 14, and were challenged with aerolized ovalbumin 1% on days 24, 26 and 28. Ovalbumin-sensitized animals received vehicle (saline and dimethyl sulfoxide, DMSO), sakuranetin (20 mg kg^–1 per mice) or dexamethasone (5 mg kg^–1 per mice) daily beginning from 24th to 29th day. Control group received saline inhalation and nasal drop vehicle. On day 29, we determined the airway hyperresponsiveness, inflammation and remodelling as well as specific IgE antibody. RANTES, IL-5, IL-4, Eotaxin, IL-10, TNF-α, IFN-γ and GMC-SF content in lung homogenate was performed by Bioplex assay, and 8-isoprostane and NF-kB activations were visualized in inflammatory cells by immunohistochemistry.

Key Results

We have demonstrated that sakuranetin treatment attenuated airway hyperresponsiveness, inflammation and remodelling; and these effects could be attributed to Th2 pro-inflammatory cytokines and oxidative stress reduction as well as control of NF-kB activation.

Conclusions and Implications

These results highlighted the importance of counteracting oxidative stress by flavonoids in this asthma model and suggest sakuranetin as a potential candidate for studies of treatment of asthma.     

Prospective study of SEVA TB peroxidase assay for cocktail antigen and antibody in the diagnosis of Tuberculosis in suspected patients attending a tertiary care hospital located in rural area

ObjectiveTo evaluate inhouse developed SEVA TB peroxidase enzyme immunoassay using cocktail of mycobacterial excretory-secretory antigens (ES-31, ES-43 & EST-6) for antibody detection and their affinity purified antibodies for antigen detection in tuberculosis suspected patients.MethodsInhouse developed SEVA TB peroxidase enzyme immunoassay was evaluated prospectively in 73 suspected pulmonary and 46 extra-pulmonary tuberculosis patients during November 2008～March 2009 in a tertiary hospital located in rural area.ResultsAssay on prospective analysis showed 100% correlation of pulmonary tuberculosis (PTB) and extra-pulmonary tuberculosis (EPTB) acid fast bacilli positivity and antitubercular treatment in 11 cases. Thirty nine PTB and 12 EPTB cases showed negative for ELISA test and were also not given antitubercular therapy. However 30 PTB and 27 EPTB cases showing ELISA positivity were neither acid fast bacilli positive nor antitubercular therapy treated. These cases may possibly have dormant infection and need further diagnosis. In EPTB cases ELISA was observed to be more useful than AFB smear test.ConclusionsThis inhouse developed user-friendly peroxidase ELISA can be used as an adjunct test of smear microscopy or culture techniques for routine screening of patients suspected of PTB or EPTB.     

A20 deletion is associated with copy number gain at the TNFA/B/C locus and occurs preferentially in translocation‐negative MALT lymphoma of the ocular adnexa and salivary glands

The genetic basis of MALT lymphoma is largely unknown. Characteristic chromosomal translocations are frequently associated with gastric and pulmonary cases, but are rare at other sites. We compared the genetic profiles of 33 ocular adnexal and 25 pulmonary MALT lymphomas by 1 Mb array–comparative genomic hybridization (CGH) and revealed recurrent 6q23 losses and 6p21.2–6p22.1 gains exclusive to ocular cases. High‐resolution chromosome 6 tile‐path array–CGH identified NF‐κB inhibitor A20 as the target of 6q23.3 deletion and TNFA/B/C locus as a putative target of 6p21.2–22.1 gain. Interphase fluorescence in situ hybridization showed that A20 deletion occurred in MALT lymphoma of the ocular adnexa (8/42 = 19%), salivary gland (2/24 = 8%), thyroid (1/9 = 11%) and liver (1/2), but not in the lung (26), stomach (45) and skin (13). Homozygous deletion was observed in three cases. A20 deletion and TNFA/B/C gain were significantly associated (p < 0.001) and exclusively found in cases without characteristic translocation. In ocular cases, A20 deletion was associated with concurrent involvement of different adnexal tissues or extraocular sites at diagnosis (p = 0.007), a higher proportion of relapse (67% versus 37%) and a shorter relapse‐free survival (p = 0.033). A20 deletion and gain at TNFA/B/C locus may thus play an important role in the development of translocation‐negative MALT lymphoma. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

White matter disease in AIDS: findings at MR imaging

A review of the magnetic resonance (MR) images of 365 patients with acquired immunodeficiency syndrome (AIDS) revealed that 112 (31%) had signal abnormalities confined to the white matter. Four patterns were observed: (a) diffuse: widespread involvement of a large area; (b) patchy: localized involvement with ill-defined margins; (c) focal: well-defined areas of involvement; and (d) punctate: small foci less than 1 cm in diameter. Clinical or pathologic findings were available in 60 of the 112 patients and were correlated with the white matter patterns seen on MR images. The diffuse pattern correlated with AIDS dementia complex (ADC), which was the most common clinical diagnosis. Patchy or punctate lesions may be seen with ADC but are less common. Focal white matter lesions were not seen in patients with ADC but were seen in all six patients with progressive multifocal leukoencephalopathy, in both patients with lymphoma, and in one patient with toxoplasmosis. The authors conclude that white matter lesions are are common in AIDS and are often secondary to direct infection of the brain with human immunodeficiency virus, which causes the ADC and usually produces a diffuse white matter pattern. Biopsy is probably not indicated in these patients. Focal white matter lesions suggest a focal infection or tumor, and biopsy may be warranted.     

Failure of computerized impedance plethysmography in the diagnostic management of patients with clinically suspected deep-vein thrombosis

Before a new diagnostic modality can be introduced in clinical medicine, the validity of both a normal and abnormal test result have to be assessed prospectively in an appropriate patient group. We have evaluated the clinical validity of a new computerized impedance plethysmography (CIP) in the diagnostic management of 381 consecutive patients with clinically suspected venous thrombosis. In patients with serially normal CIP results, the diagnosis of venous thrombosis was refuted and, consequently, they were not treated with anticoagulant therapy and all were followed up for a period of 6 months to estimate the occurrence of symptomatic venous thromboembolism. The study was prematurely terminated by the safety monitoring committee because of an unacceptably high incidence of confirmed venous thromboembolism (10 patients, 3.2%; 95% confidence interval: 1.6% to 6%), including 4 episodes of fatal pulmonary embolism. In a subsequent explanatory study using ultrasonography in 29 other symptomatic patients who had at least 2 repeated normal CIP test results, the failure of CIP to detect proximal vein thrombosis was confirmed in 4 patients (14%). The reasons for this failure are probably related to the use of a modified device to measure impedance in the CIP apparatus, resulting in a lower ability to separate patients without venous thrombosis from those with the disease. We concluded that CIP is insensitive for the detection of proximal vein thrombosis and, therefore, not clinically useful in the diagnostic management of patients with suspected venous thrombosis.