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Fulltext Rehydrated sterically stabilized phospholipid nanomicelles of budesonide for nebulization: physicochemical characterization and in vitro, in vivo evaluations

Sahib MN, Darwis Y, Peh KK, Abdulameer SA, Tan YT

Int J Nanomedicine, 2011;6:2351-66.
PMID: 22072872 DOI: 10.2147/IJN.S25363

Inhaled corticosteroids provide unique systems for local treatment of asthma or chronic obstructive pulmonary disease. However, the use of poorly soluble drugs for nebulization has been inadequate, and many patients rely on large doses to achieve optimal control of their disease. Theoretically, nanotechnology with a sustained-release formulation may provide a favorable therapeutic index. The aim of this study was to determine the feasibility of using sterically stabilized phospholipid nanomicelles of budesonide for pulmonary delivery via nebulization.

Matched MeSH terms: Bronchoalveolar Lavage Fluid/cytology
The manual MGIT system for the detection of M. tuberculosis in respiratory specimens: an experience in the University Malaya Medical Centre

Fadzilah MN, Ng KP, Ngeow YF

Malays J Pathol, 2009 Dec;31(2):93-7.
PMID: 20514851

A prospective study was conducted on 510 respiratory specimens for the presence of M. tuberculosis detected by direct acid-fast bacilli (AFB) smear examination, culture in the Manual Mycobacteria Growth Indicator Tube (BBL MGIT, Becton-Dickinson) and culture on Lowenstein-Jensen (LJ) medium. From positive BBL MGIT tubes, Ziehl-Neelsen and Gram stains were performed and subcultures were put up on LJ medium. A total of 101 (19.8%) specimens were positive by the BBL MGIT, 60 (11.8%) by primary LJ medium culture, 31 (6.1%) by direct smear examination and 29 (5.7%) by all three methods. Using primary LJ culture as the gold standard, the sensitivity and specificity of the BBL MGIT were 90% and 89.6% respectively but the sensitivity of AFB smear microscopy was only 48.3%. About half (51.1%) of the BBL MGIT false positives were due to contamination by non-AFB bacteria. The remaining false positives comprised specimens that were AFB microscopy positive but LJ culture negative. Of the AFB isolates obtained on LJ primary and sub-cultures, almost all (93.3%) were identified as Mycobacterium tuberculosis complex. The mean time-to-detection was significantly shorter (p < 0.0001) for the BBL MGIT than for LJ culture. For the former, positive results were available within 14 days for both AFB smear-positive and AFB smear-negative specimens. On the average, positive results were obtained 1.8 days earlier for direct AFB smear-positive samples than for AFB smear-negative samples. On the other hand, positive growth on LJ medium appeared after at least 33 days of incubation. These findings suggest that the BBL MGIT system will be a suitable alternative to LJ culture for the routine diagnosis of pulmonary tuberculosis, but a combination of liquid and solid cultures is still required for the highest diagnostic accuracy.

Matched MeSH terms: Bronchoalveolar Lavage Fluid
Fulltext Inflammation and lung injury in an ovine model of fluid resuscitated endotoxemic shock

Passmore MR, Byrne L, Obonyo NG, See Hoe LE, Boon AC, Diab SD, et al.

Respir Res, 2018 Nov 22;19(1):231.
PMID: 30466423 DOI: 10.1186/s12931-018-0935-4

BACKGROUND: Sepsis is a multi-system syndrome that remains the leading cause of mortality and critical illness worldwide, with hemodynamic support being one of the cornerstones of the acute management of sepsis. We used an ovine model of endotoxemic shock to determine if 0.9% saline resuscitation contributes to lung inflammation and injury in acute respiratory distress syndrome, which is a common complication of sepsis, and investigated the potential role of matrix metalloproteinases in this process.
METHODS: Endotoxemic shock was induced in sheep by administration of an escalating dose of lipopolysaccharide, after which they subsequently received either no fluid bolus resuscitation or a 0.9% saline bolus. Lung tissue, bronchoalveolar fluid (BAL) and plasma were analysed by real-time PCR, ELISA, flow cytometry and immunohistochemical staining to assess inflammatory cells, cytokines, hyaluronan and matrix metalloproteinases.
RESULTS: Endotoxemia was associated with decreased serum albumin and total protein levels, with activated neutrophils, while the glycocalyx glycosaminoglycan hyaluronan was significantly increased in BAL. Quantitative real-time PCR studies showed higher expression of IL-6 and IL-8 with saline resuscitation but no difference in matrix metalloproteinase expression. BAL and tissue homogenate levels of IL-6, IL-8 and IL-1β were elevated.
CONCLUSIONS: This data shows that the inflammatory response is enhanced when a host with endotoxemia is resuscitated with saline, with a comparatively higher release of inflammatory cytokines and endothelial/glycocalyx damage, but no change in matrix metalloproteinase levels.

Matched MeSH terms: Bronchoalveolar Lavage Fluid
Fulltext Oncostatin M-Preconditioned Mesenchymal Stem Cells Alleviate Bleomycin-Induced Pulmonary Fibrosis Through Paracrine Effects of the Hepatocyte Growth Factor

Lan YW, Theng SM, Huang TT, Choo KB, Chen CM, Kuo HP, et al.

Stem Cells Transl Med, 2017 03;6(3):1006-1017.
PMID: 28297588 DOI: 10.5966/sctm.2016-0054

Mesenchymal stem cells (MSCs) are widely considered for treatment of pulmonary fibrosis based on the anti-inflammatory, antifibrotic, antiapoptotic, and regenerative properties of the cells. Recently, elevated levels of oncostatin M (OSM) have been reported in the bronchoalveolar lavage fluid of a pulmonary fibrosis animal model and in patients. In this work, we aimed to prolong engrafted MSC survival and to enhance the effectiveness of pulmonary fibrosis transplantation therapy by using OSM-preconditioned MSCs. OSM-preconditioned MSCs were shown to overexpress type 2 OSM receptor (gp130/OSMRβ) and exhibited high susceptibility to OSM, resulting in upregulation of the paracrine factor, hepatocyte growth factor (HGF). Moreover, OSM-preconditioned MSCs enhanced cell proliferation and migration, attenuated transforming growth factor-β1- or OSM-induced extracellular matrix production in MRC-5 fibroblasts through paracrine effects. In bleomycin-induced lung fibrotic mice, transplantation of OSM-preconditioned MSCs significantly improved pulmonary respiratory functions and downregulated expression of inflammatory factors and fibrotic factors in the lung tissues. Histopathologic examination indicated remarkable amelioration of the lung fibrosis. LacZ-tagged MSCs were detected in the lung tissues of the OSM-preconditioned MSC-treated mice 18 days after post-transplantation. Taken together, our data further demonstrated that HGF upregulation played an important role in mediating the therapeutic effects of transplanted OSM-preconditioned MSCs in alleviating lung fibrosis in the mice. Stem Cells Translational Medicine 2017;6:1006-1017.

Matched MeSH terms: Bronchoalveolar Lavage Fluid
Pulmonary actinomycosis and skin sinuses

Lee JK

J Paediatr Child Health, 2007 Dec;43(12):854-5.
PMID: 18036023

A 12-year old girl presented with an unusual problem of recurrent discharging multiple skin sinuses on her right anterior and posterior chest wall for a year. There was ipsilateral lower lobe pneumonia and imaging showed multiple abscesses in her lower back muscles bilaterally. A purulent fluid was aspirated from her back muscles and the histology examination showed sulphur granules with gram positive branched filaments. She responded well to the treatment for actinomycosis with penicillin and doxycycline.

Matched MeSH terms: Bronchoalveolar Lavage Fluid
Different inflammatory mechanisms in lungs of severe and mild asthma: crosstalk of NF-kappa-B, TGFbeta1, Bax, Bcl-2, IL-4 and IgE

Abdulamir AS, Hafidh RR, Abubakar F

Scand J Clin Lab Invest, 2009;69(4):487-95.
PMID: 19347746 DOI: 10.1080/00365510902749131

To examine differences in the apoptotic, inflammatory, allergic and immunological features in the lungs of adults with asthma.

Matched MeSH terms: Bronchoalveolar Lavage Fluid
Andrographolide prevented toluene diisocyanate-induced occupational asthma and aberrant airway E-cadherin distribution via p38 MAPK-dependent Nrf2 induction

Sulaiman I, Tan K, Mohtarrudin N, Lim JCW, Stanslas J

Pulm Pharmacol Ther, 2018 12;53:39-51.
PMID: 30244166 DOI: 10.1016/j.pupt.2018.09.008

Toluene diisocyanate (TDI) is a major cause of chemical-induced occupational asthma, which contributes about 15% of global asthma burden. Resistance and compounded side effects associated with the use of corticosteroid in asthma necessitate the search for alternative drugs. Andrographolide (AGP), a naturally occurring diterpene lactone is known to exhibit various bioactivities. Its ability to ameliorate cardinal features of allergic asthma was previously suggested in an eosinophilic asthma endotype. However, its potential antiasthma activity and mechanism of action in a neutrophilic occupational asthma model, as well as its effect on epithelial dysfunction remain unknown. BALB/c mice were dermally sensitised with 0.3% TDI or acetone olive oil (AOO) vehicle on day 1 and 8, followed by 0.1% TDI intranasal challenge on days 15, 18 and 21. Endpoints were evaluated via bronchoalveolar lavage fluid (BALF) cell analysis, 2',7'-dichlorofluorescein diacetate (DCFDA) assays, immunoblotting, immunohistochemistry and methacholine challenge test. Decreases in total and differential leukocyte counts of BALF were recorded in AGP-treated animals. The compound dose-dependently reduced intracellular de-esterification of DCFDA, thus suggesting AGP's potential to inhibit intracellular reactive oxygen species (ROS). Mechanistically, the treatment prevented TDI-induced aberrant E-cadherin distribution and restored airway epithelial β-catenin at cell to cell contact site. Furthermore, AGP ameliorated TDI induced pulmonary collagen deposition. In addition, the treatment significantly upregulated pulmonary HO-1, Nrf2 and phospho-p38 levels. Airway hyperresponsiveness was markedly suppressed among AGP-treated animals. Collectively, these findings suggest AGP's protective function against TDI-induced airway epithelial barrier dysfunction and oxidative lung damage possibly through the upregulation of adherence junction proteins and the activation of p38/Nrf2 signalling. This study elucidates the therapeutic potential of AGP in the control and management of chemical-induced allergic asthma. To the best of our knowledge, the potential anti-asthma activity of AGP in TDI-induced occupational asthma has not been reported previously.

Matched MeSH terms: Bronchoalveolar Lavage Fluid
Fulltext Toll-like receptor 2 and 4 have opposing roles in the pathogenesis of cigarette smoke-induced chronic obstructive pulmonary disease

Haw TJ, Starkey MR, Pavlidis S, Fricker M, Arthurs AL, Nair PM, et al.

Am. J. Physiol. Lung Cell Mol. Physiol., 2018 02 01;314(2):L298-L317.
PMID: 29025711 DOI: 10.1152/ajplung.00154.2017

Chronic obstructive pulmonary disease (COPD) is the third leading cause of morbidity and death and imposes major socioeconomic burdens globally. It is a progressive and disabling condition that severely impairs breathing and lung function. There is a lack of effective treatments for COPD, which is a direct consequence of the poor understanding of the underlying mechanisms involved in driving the pathogenesis of the disease. Toll-like receptor (TLR)2 and TLR4 are implicated in chronic respiratory diseases, including COPD, asthma and pulmonary fibrosis. However, their roles in the pathogenesis of COPD are controversial and conflicting evidence exists. In the current study, we investigated the role of TLR2 and TLR4 using a model of cigarette smoke (CS)-induced experimental COPD that recapitulates the hallmark features of human disease. TLR2, TLR4, and associated coreceptor mRNA expression was increased in the airways in both experimental and human COPD. Compared with wild-type (WT) mice, CS-induced pulmonary inflammation was unaltered in TLR2-deficient ( Tlr2-/-) and TLR4-deficient ( Tlr4-/-) mice. CS-induced airway fibrosis, characterized by increased collagen deposition around small airways, was not altered in Tlr2-/- mice but was attenuated in Tlr4-/- mice compared with CS-exposed WT controls. However, Tlr2-/- mice had increased CS-induced emphysema-like alveolar enlargement, apoptosis, and impaired lung function, while these features were reduced in Tlr4-/- mice compared with CS-exposed WT controls. Taken together, these data highlight the complex roles of TLRs in the pathogenesis of COPD and suggest that activation of TLR2 and/or inhibition of TLR4 may be novel therapeutic strategies for the treatment of COPD.

Matched MeSH terms: Bronchoalveolar Lavage Fluid