A recent focus meeting on Controlling Acute Inflammation was held in London, April 27-28, 2006, organized by D.W. Gilroy and S.D. Brain for the British Pharmacology Society. We concluded at the ...meeting that a consensus report was needed that addresses the rapid progress in this emerging field and details how the specific study of resolution of acute inflammation provides leads for novel anti-inflammatory therapeutics, as well as defines the terms and key components of interest in the resolution process within tissues as appreciated today. The inflammatory response protects the body against infection and injury but can itself become dysregulated with deleterious consequences to the host. It is now evident that endogenous biochemical pathways activated during defense reactions can counter-regulate inflammation and promote resolution. Hence, resolution is an active rather than a passive process, as once believed, which now promises novel approaches for the treatment of inflammation-associated diseases based on endogenous agonists of resolution.--Serhan, C. N., Brain, S. D., Buckley, C. D., Gilroy, D. W., Haslett, C., O'Neill, L. A. J., Perretti, M., Rossi, A. G., Wallace, J. L. Resolution of inflammation: state of the art, definitions and terms.
Highlights ► TLRs have been implicated in the pathogenesis of many inflammatory diseases and cancer. ► TLRs are being targeted by agonists or antagonists to control key processes in innate immunity. ...► These TLR targeted therapeutics have clinical applications in a wide range of conditions. ► Many are undergoing evaluation in clinical trials.
Atherosclerosis is the cause of morbiditiy for 70% of patients with type 2 diabetes. In both of these diseases, a protein complex known as the inflammasome is stimulated to activate interleukin-1β ...(IL-1β) and IL-18, which are pathogenic inflammatory cytokines. Triggers for the inflammasome are obesity-related factors, such as cholesterol crystals in atherosclerosis, or hyperglycemia, ceramides, and islet amyloid polypeptide in type 2 diabetes. Therapeutics that target IL-1β in clinical trials for type 2 diabetes might also decrease the incidence of atherosclerosis.
Summary
An understanding of lipopolysaccharide (LPS) signal transduction is a key goal in the effort to provide a molecular basis for the lethal effect of LPS during septic shock and point the way to ...novel therapies. Rapid progress in this field during the last 6 years has resulted in the discovery of not only the receptor for LPS – Toll‐like receptor 4 (TLR4) – but also in a better appreciation of the complexity of the signalling pathways activated by LPS. Soon after the discovery of TLR4, the formation of a receptor complex in response to LPS, consisting of dimerized TLR4 and MD‐2, was described. Intracellular events following the formation of this receptor complex depend on different sets of adapters. An early response, which is dependent on MyD88 and MyD88‐like adapter (Mal), leads to the activation of nuclear factor‐κB (NF‐κB). A later response to LPS makes use of TIR‐domain‐containing adapter‐inducing interferon‐β (TRIF) and TRIF‐related adapter molecule (TRAM), and leads to the late activation of NF‐κB and IRF3, and to the induction of cytokines, chemokines, and other transcription factors. As LPS signal transduction is an area of intense research and rapid progress, this review is intended to sum up our present understanding of the events following LPS binding to TLR4, and we also attempt to create a model of the signalling pathways activated by LPS.
Patients presenting with non-ST-elevation acute coronary syndrome (NSTE-ACS) are at risk of early death. This may be reduced by timely assessment and treatment.
The purpose of this study was to ...evaluate if Nurse-led Early Triage (NET) in the coronary care unit (CCU) can improve time to assessment and management of NSTE-ACS patients.
Data on 79 consecutive chest pain patients admitted pre-NET to the acute admissions unit (AAU) and on 103 patients admitted in the first six months of the NET service in CCU, was re-examined and compared to subsequent data obtained on 92 patients admitted via NET five years later, in order to re-evaluate the service.
NET resulted in significant improvements in: the number of patients with chest pain who had their 12-lead electrocardiogram (ECG) performed within 10 min of admission (94% vs 32%, p<0.001); the number of high-risk NSTE-ACS patients prescribed clopidogrel (72% vs 42%, p<0.01); and the number being managed in CCU (82% vs 34%, p<0.01). Comparison of the NET service at five years with the pre-NET service demonstrated measurable benefits were sustained (p<0.01) for the same comparative end points. There were no significant differences in these end-points of time to ECG, clopidogrel prescription nor management in CCU for high-risk patients between the NET groups at six months and five years, demonstrating that current triage is as effective as when first introduced.
This study demonstrated the positive impact of nurse-led early triage for NSTE-ACS patients and that initial benefits have been sustained.
Macrophages play diverse roles including but not limited to homeostatic clearance, detection of invading pathogens and induction of the adaptive immune response. Since their discovery, it has become ...clear that Toll-like receptors (TLRs) can play a major role in these macrophage functions. This review will describe the TLRs, their signalling pathways and their role in macrophage function.
Effect of patient satisfaction on outcomes of care Dubina, Meghan I; O'Neill, Jenna L; Feldman, Steven R
Expert review of pharmacoeconomics & outcomes research,
10/1/2009, 2009-10-00, 20091001, Letnik:
9, Številka:
5
Journal Article