functional responsiveness
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Pathogens ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1545
Author(s):  
Tomasz Wollny ◽  
Tamara Daniluk ◽  
Ewelina Piktel ◽  
Urszula Wnorowska ◽  
Anna Bukłaha ◽  
...  

Irritable bowel syndrome (IBS) is a common, chronic, functional disorder with a large impact on world population. Its pathophysiology is not completely revealed; however, it is certain that dysregulation of the bidirectional communications between the central nervous system (CNS) and the gut leads to motility disturbances, visceral hypersensitivity, and altered CNS processing characterized by differences in brain structure, connectivity and functional responsiveness. Emerging evidence suggests that gut microbiota exerts a marked influence on the host during health and disease. Gut microbiome disturbances can be also important for development of IBS symptoms and its modulation efficiently contributes to the therapy. In this work, we review the current knowledge about the IBS therapy, the role of gut microbiota in pathogenesis of IBS, and we discuss that its targeting may have significant impact on the effectiveness of IBS therapy.



2021 ◽  
Vol 365 ◽  
pp. 104363
Author(s):  
Ece Tavukcuoglu ◽  
Utku Horzum ◽  
Ahmet Cagkan Inkaya ◽  
Serhat Unal ◽  
Gunes Esendagli


Author(s):  
Yana Roka-Moiia ◽  
Samuel Miller-Gutierrez ◽  
Daniel E. Palomares ◽  
Joseph E. Italiano ◽  
Jawaad Sheriff ◽  
...  

Objective: Mechanical circulatory support has emerged as lifesaving therapy for patients with advanced heart failure. However, mechanical circulatory support remains limited by a paradoxical coagulopathy accompanied by both thrombosis and bleeding. While mechanisms of mechanical circulatory support thrombosis are increasingly defined, mechanical circulatory support-related bleeding, as related to shear-mediated alteration of platelet function, remains poorly understood. We tested the hypothesis that platelet exposure to elevated shear stress, while a defined prothrombotic activator of platelets, coordinately induces downregulation of key platelet adhesion receptors GPIb (glycocalicin)-IX-V, α IIb β 3 , and P-selectin, thus decreasing platelet functional responsiveness to physiological stimuli. Approach and Results: Human gel-filtered platelets were exposed to continuous or pulsatile shear stress in vitro. Surface expression of platelet receptors and platelet-derived microparticle generation were quantified by flow cytometry. Shedding of receptor soluble forms were assessed via ELISA, and platelet aggregation was measured by optical aggregometry. We demonstrate that platelet exposure to elevated shear stress led to a downregulation of GPIb and α IIb β 3 receptors on platelets with a progressive increase in the generation of platelet-derived microparticles expressing elevated levels of α IIb β 3 and GPIb on their surface. No shear-mediated shedding of GPIb and β 3 subunit soluble fragments was detected. Soluble P-selectin was extensively shed from platelets, while surface expression of P-selectin on platelets and microparticles was not significantly altered by shear. Shear-mediated downregulation of GPIb, α IIb β 3 , and P-selectin on platelets was associated with an evident decrease of platelet aggregatory response induced by ADP and TRAP 6 (thrombin receptor activating peptide 6). Conclusions: Our data clearly indicate that accumulation of shear stress, consistent with supraphysiologic conditions characterizing device-supported circulation (1) induces adequate platelet degranulation, yet (2) causes downregulation of primary platelet adhesion receptors via ejection of receptor-enriched platelet-derived microparticles, thus mechanistically limiting platelet activation and the aggregatory response.





2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Paul H. Naccache

This review presents a summary of signalling events related to the activation of human polymorphonuclear neutrophils by a variety of soluble and particulate agonists. It is not intended as a comprehensive review of this vast field or as a presentation of the multiple new aspects of neutrophil functions that are being documented at an ever faster rate. Its aim is rather to focus on multiple aspects of major signalling pathways that, in the view of this reviewer, are currently shadowed by present trends and to provide the core evidence for their implication and the limitations of our present knowledge. More specifically, this review starts with cell surface receptors and some of their functional and biological properties and then moves on to downstream transducers (G proteins) and effectors (the phosphoinositide, tyrosine kinases, and cyclic nucleotide pathways). Classical second messengers (calcium, protein kinase C, polyphosphoinositides, and cyclic nucleotides) are emphasized. It is hoped that this presentation will not only remind present-day investigators of the central role these pathways play in the regulation of the functional responsiveness of neutrophils, but that it will also highlight some of the areas deserving additional investigation.



2012 ◽  
Vol 36 (12) ◽  
pp. 1171-1183 ◽  
Author(s):  
Yulia Koryakina ◽  
Stacie M. Jones ◽  
Lawrence E. Cornett ◽  
Kathryn Seely ◽  
Lisa Brents ◽  
...  


2011 ◽  
Vol 8 (2) ◽  
pp. 181-190 ◽  
Author(s):  
Jameel Dennis ◽  
Magdalena K. Morgan ◽  
Martin R. Graf ◽  
Babette Fuss




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