A concise synthesis of the potent inflammatory mediator 5-oxo-ETE

MedChemComm ◽  
2012 ◽  
Vol 3 (2) ◽  
pp. 195-198 ◽  
Author(s):  
Rahul Tyagi ◽  
Bharat Shimpukade ◽  
Stefanie Blättermann ◽  
Evi Kostenis ◽  
Trond Ulven
Keyword(s):  
Inflammatory Mediator ◽  
Potent Inflammatory Mediator

Effects of Platelet Activating Factor on Vascular Permeability of the Middle Ear Mucosa

1997 ◽  
Vol 106 (7) ◽  
pp. 604-607 ◽  
Author(s):  
Chung-Ku Rhee ◽  
Yong-Soo Park ◽  
Timothy T. K. Jung ◽  
Steven A. Long ◽  
David Davamony
Keyword(s):  
Vascular Permeability ◽  
Middle Ear ◽  
Normal Saline ◽  
Evans Blue ◽  
Inflammatory Mediator ◽  
Otitis Media With Effusion ◽  
Platelet Activating Factor ◽  
Control Group ◽  
Middle Ear Mucosa ◽  
Potent Inflammatory Mediator

Platelet activating factor (PAF), a potent inflammatory mediator, seems to play a significant role in the pathogenesis of otitis media with effusion (OME), along with other inflammatory mediators such as leukotrienes and prostaglandins. The purpose of this study was to investigate the effect of PAF on the vascular permeability of middle ear mucosa, in an experimental OME model using chinchillas. We injected PAF in doses of 1, 4, 8, and 16 μg and normal saline as a control into the bullae of chinchillas. Vascular permeability was measured by the Evans blue vital dye technique. All the PAF-injected animals showed a significant increase in middle ear vascular permeability compared to the control group. This study demonstrated that PAF in the middle ear cavity contributes significantly to the development of OME by increasing the vascular permeability of the middle ear mucosa.

Secretory phospholipase A2 predicts impending acute chest syndrome in sickle cell disease

Blood ◽  
2000 ◽  
Vol 96 (9) ◽  
pp. 3276-3278
Author(s):  
Lori A. Styles ◽  
Anton J. Aarsman ◽  
Elliott P. Vichinsky ◽  
Frans A. Kuypers
Keyword(s):  
Sickle Cell Disease ◽  
Phospholipase A2 ◽  
Cause Of Death ◽  
Sickle Cell ◽  
Inflammatory Mediator ◽  
Acute Chest Syndrome ◽  
Secretory Phospholipase A2 ◽  
Cell Disease ◽  
Secretory Phospholipase ◽  
Potent Inflammatory Mediator

Acute chest syndrome (ACS) is the leading cause of death in sickle cell disease. Severe ACS often develops in the course of a vaso-occlusive crisis (VOC), but currently there are no predictors for its development. Secretory phospholipase A2(sPLA2), a potent inflammatory mediator, is elevated in ACS, and previous work suggests that sPLA2 predicts impending ACS. We prospectively evaluated sPLA2concentration during 21 admissions for VOC; 6 of these patients went on to develop ACS. Elevation of sPLA2 was detected all 6 patients 24 to 48 hours before ACS was clinically diagnosed. Adding the requirement for fever raised the specificity of sPLA2 to 87% while retaining 100% sensitivity. These data indicate that sPLA2 can be useful in alerting the clinician to patients with impending ACS. In addition, sPLA2 may be useful for instituting early therapies to prevent or reduce the clinical morbidity of ACS.

Secretory phospholipase A2 predicts impending acute chest syndrome in sickle cell disease

Blood ◽  
2000 ◽  
Vol 96 (9) ◽  
pp. 3276-3278 ◽  
Author(s):  
Lori A. Styles ◽  
Anton J. Aarsman ◽  
Elliott P. Vichinsky ◽  
Frans A. Kuypers
Keyword(s):  
Sickle Cell Disease ◽  
Phospholipase A2 ◽  
Cause Of Death ◽  
Sickle Cell ◽  
Inflammatory Mediator ◽  
Acute Chest Syndrome ◽  
Secretory Phospholipase A2 ◽  
Cell Disease ◽  
Secretory Phospholipase ◽  
Potent Inflammatory Mediator

Abstract Acute chest syndrome (ACS) is the leading cause of death in sickle cell disease. Severe ACS often develops in the course of a vaso-occlusive crisis (VOC), but currently there are no predictors for its development. Secretory phospholipase A2(sPLA2), a potent inflammatory mediator, is elevated in ACS, and previous work suggests that sPLA2 predicts impending ACS. We prospectively evaluated sPLA2concentration during 21 admissions for VOC; 6 of these patients went on to develop ACS. Elevation of sPLA2 was detected all 6 patients 24 to 48 hours before ACS was clinically diagnosed. Adding the requirement for fever raised the specificity of sPLA2 to 87% while retaining 100% sensitivity. These data indicate that sPLA2 can be useful in alerting the clinician to patients with impending ACS. In addition, sPLA2 may be useful for instituting early therapies to prevent or reduce the clinical morbidity of ACS.

Platelet-activating factor stimulates resorption by rabbit osteoclasts in vitro

1993 ◽  
Vol 264 (1) ◽  
pp. E74-E81 ◽  
Author(s):  
Z. G. Zheng ◽  
D. A. Wood ◽  
S. M. Sims ◽  
S. J. Dixon
Keyword(s):  
Inflammatory Mediator ◽  
Inflammatory Diseases ◽  
Platelet Activating Factor ◽  
Time Lapse ◽  
Osteoclastic Resorption ◽  
Planar Area ◽  
Osteoclast Function ◽  
Resorptive Activity ◽  
Potent Inflammatory Mediator

We have shown previously that platelet-activating factor (PAF), a potent inflammatory mediator, acts directly on isolated rat osteoclasts to elevate cytosolic free Ca2+ concentration ([Ca2+]i). The purpose of this study was to examine the effects of PAF on osteoclast function. Osteoclasts were isolated from the long bones of neonatal rabbits and studied in three ways. [Ca2+]i of fura-2-loaded osteoclasts was monitored by microspectrofluorimetry. In 9 out of 16 cells tested, PAF (10–100 nM) caused elevation of [Ca2+]i that peaked then returned to baseline. In contrast, the biologically inactive precursor and metabolite of PAF, lyso-PAF, was without effect. Using time-lapse videomicroscopy, we found that PAF elicited retraction of peripheral pseudopods. Although calcitonin induced sustained retraction and immobility, the response to PAF was transient and, within 30 min, pseudopods reformed. To assess effects of PAF on resorptive activity, osteoclasts were cultured on dentin slices for 48 h in the presence of vehicle, PAF (200 nM), or calcitonin (100 ng/ml). PAF increased the area of individual resorption pits (from control values of 1,660 +/- 110 to 2,240 +/- 200 microns2, P < 0.05) and the total planar area resorbed per unit area of substrate (from 7.6 +/- 1.6 to 14.5 +/- 3.1 x 10(4) microns2/cm2, P < 0.025). As expected, calcitonin significantly decreased resorptive activity. These data indicate that PAF activates osteoclastic resorption. PAF may play a role in mediating the resorption of bone and mineralized cartilage in inflammatory diseases such as rheumatoid arthritis and periodontitis.

scholarly journals Capsular polysaccharide switching in Streptococcus suis modulates host cell interactions and virulence

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Masatoshi Okura ◽  
Jean-Philippe Auger ◽  
Tomoyuki Shibahara ◽  
Guillaume Goyette-Desjardins ◽  
Marie-Rose Van Calsteren ◽  
...  
Keyword(s):  
Host Cell ◽  
Capsular Polysaccharide ◽  
Inflammatory Mediator ◽  
Streptococcus Suis ◽  
Cell Interactions ◽  
Inflammatory Mediator Production ◽  
Composition And Structure ◽  
Infection Models ◽  
Host Cell Interactions ◽  
Blood Dendritic Cell

AbstractThe capsular polysaccharide (CPS) of Streptococcus suis defines various serotypes based on its composition and structure. Though serotype switching has been suggested to occur between S. suis strains, its impact on pathogenicity and virulence remains unknown. Herein, we experimentally generated S. suis serotype-switched mutants from a serotype 2 strain that express the serotype 3, 4, 7, 8, 9, or 14 CPS. The effects of serotype switching were then investigated with regards to classical properties conferred by presence of the serotype 2 CPS, including adhesion to/invasion of epithelial cells, resistance to phagocytosis by macrophages, killing by whole blood, dendritic cell-derived pro-inflammatory mediator production and virulence using mouse and porcine infection models. Results demonstrated that these properties on host cell interactions were differentially modulated depending on the switched serotypes, although some different mutations other than loci of CPS-related genes were found in each the serotype-switched mutant. Among the serotype-switched mutants, the mutant expressing the serotype 8 CPS was hyper-virulent, whereas mutants expressing the serotype 3 or 4 CPSs had reduced virulence. By contrast, switching to serotype 7, 9, or 14 CPSs had little to no effect. These findings suggest that serotype switching can drastically alter S. suis virulence and host cell interactions.

scholarly journals Recurrent Clostridioides difficile infection can be predicted using inflammatory mediator and toxin activity levels

2020 ◽  
Vol 41 (S1) ◽  
pp. s77-s78
Author(s):  
Jonathan Motyka ◽  
Aline Penkevich ◽  
Vincent Young ◽  
Krishna Rao
Keyword(s):  
Machine Learning ◽  
Inflammatory Mediators ◽  
Inflammatory Mediator ◽  
Characteristic Curve ◽  
Receiver Operator Characteristic Curve ◽  
Sensitivity Analyses ◽  
Activity Levels ◽  
Clinical Criteria ◽  
Clostridioides Difficile ◽  
Potential Biomarker

Background:Clostridioides difficile infection (CDI) frequently recurs after initial treatment. Predicting recurrent CDI (rCDI) early in the disease course can assist clinicians in their decision making and improve outcomes. However, predictions based on clinical criteria alone are not accurate and/or do not validate other results. Here, we tested the hypothesis that circulating and stool-derived inflammatory mediators predict rCDI. Methods: Consecutive subjects with available specimens at diagnosis were included if they tested positive for toxigenic C. difficile (+enzyme immunoassay [EIA] for glutamate dehydrogenase and toxins A/B, with reflex to PCR for the tcdB gene for discordants). Stool was thawed on ice, diluted 1:1 in PBS with protease inhibitor, centrifuged, and used immediately. A 17-plex panel of inflammatory mediators was run on a Luminex 200 machine using a custom antibody-linked bead array. Prior to analysis, all measurements were normalized and log-transformed. Stool toxin activity levels were quantified using a custom cell-culture assay. Recurrence was defined as a second episode of CDI within 100 days. Ordination characterized variation in the panel between outcomes, tested with a permutational, multivariate ANOVA. Machine learning via elastic net regression with 100 iterations of 5-fold cross validation selected the optimal model and the area under the receiver operator characteristic curve (AuROC) was computed. Sensitivity analyses excluding those that died and/or lived >100 km away were performed. Results: We included 186 subjects, with 95 women (51.1%) and average age of 55.9 years (±20). More patients were diagnosed by PCR than toxin EIA (170 vs 55, respectively). Death, rCDI, and no rCDI occurred in 32 (17.2%), 36 (19.4%), and 118 (63.4%) subjects, respectively. Ordination revealed that the serum panel was associated with rCDI (P = .007) but the stool panel was not. Serum procalcitonin, IL-8, IL-6, CCL5, and EGF were associated with recurrence. The machine-learning models using the serum panel predicted rCDI with AuROCs between 0.74 and 0.8 (Fig. 1). No stool inflammatory mediators independently predicted rCDI. However, stool IL-8 interacted with toxin activity to predict rCDI (Fig. 2). These results did not change significantly upon sensitivity analysis. Conclusions: A panel of serum inflammatory mediators predicted rCDI with up to 80% accuracy, but the stool panel alone was less successful. Incorporating toxin activity levels alongside inflammatory mediator measurements is a novel, promising approach to studying stool-derived biomarkers of rCDI. This approach revealed that stool IL-8 is a potential biomarker for rCDI. These results need to be confirmed both with a larger dataset and after adjustment for clinical covariates.Funding: NoneDisclosure: Vincent Young is a consultant for Bio-K+ International, Pantheryx, and Vedanta Biosciences.

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