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Genetics and genomics of idiopathic pulmonary fibrosis
Published in Muhunthan Thillai, David R Moller, Keith C Meyer, Clinical Handbook of Interstitial Lung Disease, 2017
Susan K Mathai, David A Schwartz
Other studies of gene expression profiles in lung tissue have also attempted to use genome-scale gene expression data to identify genes and pathways active during ‘acute exacerbations’ of IPF (IPF-AE), periods of accelerated decline in respiratory function that occur in patients with stable or less rapidly progressive disease (47,55). Globally, the gene expression profile of lung tissue from IPF-AE subjects is nearly identical to that of stable IPF when both were compared to control samples, but when compared directly, 579 genes, many related to stress responses, were significantly differentially expressed (55). Even in the direct comparison of IPF-AE to stable IPF, inflammatory genes were not differentially expressed, arguing against a direct role for inflammation or acute viral infection in IPF-AE pathogenesis. Alpha-defensin gene expression and plasma alpha-defensin levels were elevated in IPF-AE, suggesting that these could be potential biomarkers in this disease and that epithelial cells are important in IPF-AE processes (55).
Orthopaedic Implant–Associated Infections: Pathogenesis, Clinical Presentation and Management
Published in Huiliang Cao, Silver Nanoparticles for Antibacterial Devices, 2017
Determination of leukocytes and neutrophil fraction in synovial fluid is important, since it allows the detection of culture-negative PJI according to the IDSA definition (Table 13.1). The published cutoff values show a sensitivity and specificity of nearly or even more than 90%. In hip arthroplasties, Schinsky et al. (2008) suggested >4200 WBC/μL and >80% polymorphonuclear (PMN) cells for the differential count. In knee arthroplasties, the cutoff values are lower than those in hip arthroplasties. Trampuz et al. (2004) found a value of >1700 WBC/μL and >65% PMN cells for the differential count. If the synovial fluid is examined within the first 6 weeks after surgery, the leukocyte counts are still increased by the surgical trauma and hence difficult to interpret. Proposed cutoff values are >25,000 leukocytes/μL (Bedair et al. 2011). In the future, determination of alpha-defensin, which is a cationic microbicidal peptide in neutrophils, may replace the determination of leukocyte counts in synovia (Deirmengian et al. 2015). However, a direct comparison with synovial leukocytes is still missing.
Host–Biofilm Interactions at Mucosal Surfaces and Implications in Human Health
Published in Chaminda Jayampath Seneviratne, Microbial Biofilms, 2017
Nityasri Venkiteswaran, Kassapa Ellepola, Chaminda Jayampath Seneviratne, Yuan Kun Lee, Kia Joo Puan, Siew Cheng Wong
In humans, a wide variety of proteins and peptides exhibit antimicrobial activity. Host-derived antimicrobial peptides (AMPs) form an essential part of the innate immune system. Defensins were the first natural antimicrobial peptides to be described in mammalian cells. Originally isolated from epithelial cells and neutrophils, they are small cationic peptides and function by binding to the bacterial plasma membrane. Defensins cause a disruption of the membrane integrity resulting in inhibition of DNA, RNA and protein synthesis. The nature of the interaction allows defensins to target both Gram-positive and Gram-negative bacteria, fungi and enveloped viruses. Two classes of defensins have been described in humans, alpha and beta. Both types consist of six conserved cysteine residues. Alpha-defensins are synthesised by polymorphonuclear leukocytes and Paneth cells. In contrast to alpha-defensins, beta-defensins are secreted by epithelial cells in the respiratory, gastrointestinal and urinary tracts. Defensins are secreted at low levels under normal physiological conditions but can be induced in response to microbial infections. Since their discovery, other functional roles have been ascribed to defensins [139]. For instance, alpha-defensins such as HNP1-3 have been demonstrated to function as chemoattractants for dendritic cells and naïve CD4 and CD8 T cells [140]. Alpha-defensins derived from human neutrophils have been shown to neutralise the anthrax lethal toxin [141], diphtheria toxin and Pseudomonas exotoxin A [141]. Recent investigations on human beta-defensin-3 have revealed its link to oral cancer [142].
Accuracy of blood-tests and synovial fluid-tests in the diagnosis of periprosthetic joint infections
Published in Expert Review of Anti-infective Therapy, 2020
Emanuele Chisari, Javad Parvizi
Alpha defensin is an antimicrobial peptide released by activated neutrophils as a response to a bacterial infection. It can be either measured qualitatively through the Alpha Defensin Lateral Flow (ADLF) test or quantitatively through an enzyme-linked immunosorbent assay (ELISA) [13,67]. Recent studies comparing different criteria for PJI and determining the sensitivity and specificity of different alpha-defensin tests showed that there was no significant difference in the sensitivity and specificity when using ADLF or ELISA methods for the detection of alpha defensin in synovial fluid [67]. With previous PJI criteria, its sensitivity was attested to be from 67% to 77%, with a specificity of 99% [13,67–69]. However, when the current definition was used, the ADLF test showed lower sensitivity (54.4%), keeping a high specificity of 99.3% (Table 2.) [13,67]. Even though this test is, due to its low sensitivity, not suitable for screening, it can still be used as a confirmatory test for early acute PJI (up to 6 weeks) when the synovial WBC is less reliable.
Assessing an alpha-defensin lateral flow device for diagnosing septic arthritis: reporting on a false-negative case and a false-positive case
Published in Modern Rheumatology Case Reports, 2020
Atsushi Narita, Akemi Suzuki, Taku Nakajima, Yuya Takakubo, Juji Ito, Akiko Sasaki, Michiaki Takagi
The presence of alpha-defensin (αD), an antimicrobial peptide released by neutrophils in response to bacterial pathogens, in the synovial fluid has been proposed as a novel diagnostic biomarker [4]. αD has been described as a biomarker in periprosthetic joint infection (PJI), and there are several reports on the usefulness of αD for diagnosing PJI [4,5]. Recently, the presence of synovial αD has been included as a minor criterion for diagnosing PJI [6]. There are two commercially available methods for measuring αD in synovial fluid: the enzyme-linked immunosorbent assay (ELISA)-based Synovasure® αD immunoassay (Zimmer Biomet, Warsaw, IN, USA), which gives a readout within 24 h, and the Synovasure® lateral flow test (Zimmer Biomet), which gives a perioperative readout in about 10 min [4,5]. However, some reports suggest that the lateral flow device is less sensitivity than the laboratory-based alpha-defensin test in diagnosing PJI [7–9].
Effects of Protein Versus Carbohydrate Supplementation on Markers of Immune Response in Master Triathletes: A Randomized Controlled Trial
Published in Journal of the American College of Nutrition, 2019
Fernando Naclerio, Eneko Larumbe-Zabala, Marcos Seijo, Nadia Ashrafi, Birthe V. Nielsen, Conrad P. Earnest
Defensins, including alpha-defensins, are antimicrobial peptides (AMP) that contribute to the mucosal host defense acting as the first line of action against invading pathogens (5). Salivary human neutrophil peptides (mainly human neutrophil peptides [HNP] 1–3) encompass a specific group of alpha-defensins that increases in response to the respiratory distress syndrome (6). However, their response to an acute or chronic exercise stimulus is still unclear. Acute increases in the concentration of HNP1–3 and other AMP (i.e., LL-37, LL-37, L Lactoferrin, and Lysozyme) have been reported after 2.5 hours (7,8) or 45 minutes (9) of submaximal (60% to 75% of 2peak) endurance exercises. Conversely, decreases in basal levels and secretion rates of HNP1–3 were also observed after an 8-week resistance-training program in young males who regularly consumed a postworkout beverage containing hydrolyzed beef proteins and carbohydrates (10). As lower basal levels of HNP1–3 have been associated with reduced risks against virus and infections (11), along with higher performance productions (6), the decreased concentrations in athletes have been connected with a better capacity to overcome the degree of stress determined by a given exercise protocol (10).