.-To examine the role of the fibrinolytic system in LPS-induced airway disease, we compared the effect of a chronic LPS challenge in plasminogen activator inhibitor-deficient (C57BL/6J PAI-1Ϫ/Ϫ ) mice and wild-type (WT) C57BL/6J mice. Physiological and biological assessments were performed, immediately after, and 4 wk after an 8-wk exposure to LPS or saline. Immediately after the LPS exposure, WT mice had increased estimates of airway reactivity to methacholine compared with C57BL/6J PAI-1Ϫ/Ϫ mice; however, airway inflammation was similar in both LPS-exposed groups. Significant increases in both active transforming growth factor (TGF)-1 and active matrix metalloproteinase (MMP)-9 was detected after LPS exposure in WT but not C57BL/6J PAI-1Ϫ/Ϫ mice. C57BL/6JPAI-1Ϫ/Ϫ mice showed significantly less TGF-1 in the lavage and higher MMP-9 in the lung tissue than WT mice at the end of exposure and 4 wk later. After LPS exposure, both WT and C57BL/6J PAI-1Ϫ/Ϫ mice had substantial expansion of the subepithelial area of the medium [diameter (d) ϭ 90-129 m]-and large (d Ͼ 129 m)-size airways when compared with saline-exposed mice. Subepithelial fibrin deposition was prevalent in WT mice but diminished in C57BL/6J PAI-1Ϫ/Ϫ . PAI-1 expression by nonciliated bronchial epithelial cells was enhanced in LPS-exposed WT mice compared with the saline-exposed group. Four weeks after LPS inhalation, airway hyperreactivity and the expansion of the subepithelial area in the medium and large airways persisted in WT but not C57BL/6J PAI-1Ϫ/Ϫ mice. We conclude that an active fibrinolytic system can substantially alter the development and resolution of the postinflammatory airway remodeling observed after chronic LPS inhalation. airway remodeling; lung inflammation; transforming growth factor-1; matrix metalloproteinase-9; plasminogen activator inhibitor ONE ASPECT OF THE ASTHMATIC AIRWAY that is in need of further attention is the mechanisms that regulate the turnover of the extracellular matrix adjacent to the airway epithelia. Components of the fibrinolytic system are among the various factors that have been implicated in the balance between lung tissue injury and repair, or extracellular matrix (ECM) degradation and synthesis. Plasmin, plasminogen activators (PAs), and their inhibitors (PAIs) are the key molecules of the fibrinolytic cascade. The conversion of plasminogen to plasmin is controlled by two distinct types of PAs, tissue type (tPA) and urokinase type (uPA) (35). Plasmin itself is known to digest fibrin(ogen), lyse several other components of ECM (laminin, fibronectin), and to convert matrix metalloproteinases (MMPs) from their latent to active form (27). Two MMPs, MMP-2 and MMP-9, are known to degrade not only denaturated collagens, but also ECM proteins, including type I and IV collagen, fibronectin, and laminin (1). On the other hand, uPA, being a serine protease, acts synergistically, degrading ECM molecules (6). The action of the PAs is opposed and therefore regulated by inhibitors PAI-1, PAI-2, and PAI-3. PAI-1 inhib...
Seasonal influenza virus causes significant morbidity and mortality each year. Point-of-care (POC) testing using rapid influenza diagnostic tests (RIDTs), immunoassays that detect viral antigens, are often used for diagnosis by physician offices and urgent care centers. These tests are rapid but lack sensitivity, which is estimated to be 50 to 70%. Testing by PCR is highly sensitive and specific, but historically these assays have been performed in centralized clinical laboratories necessitating specimen transport and increasing the time to result. Recently, Clinical Laboratory Improvement Amendments (CLIA)-waived, POC PCR influenza assays have been developed with >95% sensitivity and specificity compared to centralized PCR assays. To determine the clinical impact of a POC PCR test for influenza, we compared antimicrobial prescribing patterns of one urgent care location using the Cobas LIAT Influenza A/B assay (LIAT assay; Roche Diagnostics, Indianapolis, IN) to other urgent care centers in our health system using traditional RIDT, with negative specimens being reflexed to PCR. Antiviral prescribing was lower in patients with a negative LIAT PCR result (2.3%) than in patients with a negative RIDT result (25.3%; P < 0.005). Antivirals were prescribed more often in patients that tested positive by LIAT PCR (82.4%) than in those testing positive by either RIDT or reflex PCR (69.9%; P < 0.05). Antibacterial prescriptions for patients testing negative by LIAT PCR were higher (44.5%) than for those testing negative by RIDT (37.7%), although the difference was not statistically significant. In conclusion, having results from a PCR POC test during the clinic visit improved antiviral prescribing practices compared to having rapid results from an RIDT.
Syndromic panels have allowed clinical microbiology laboratories to rapidly identify bacteria, viruses, fungi, and parasites and are now fully integrated into the standard testing practices of many clinical laboratories. To maximize the benefit of syndromic testing, laboratories must implement strict measures to ensure that syndromic panels are being used responsibly. This article discusses commercially available syndromic panels, the benefits and limitations of testing, and how diagnostic and laboratory stewardship can be used to optimize testing and improve patient care while keeping costs at a minimum.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.