The FPR2-induced rise in cytosolic calcium in human neutrophils relies on an emptying of intracellular calcium stores and is inhibited by a gelsolin-derived PIP2-binding peptide

<p>Abstract</p> <p>Background</p> <p>The molecular basis for neutrophil recognition of chemotactic peptides is their binding to specific G-protein-coupled cell surface receptors (GPCRs). Human neutrophils express two pattern recognition GPCRs, FPR1 and FPR2, which belong to the family of formyl peptide receptors. The high degree of homology between these two receptors suggests that they share many functional and signal transduction properties, although they exhibit some differences with respect to signaling. The aims of this study were to determine whether FPR2 triggers a unique signal that allows direct influx of extracellular calcium without the emptying of intracellular calcium stores, and whether the gelsolin-derived PIP₂-binding peptide, PBP10, selectively inhibits FPR2-mediated transient rise in intracellular Ca²⁺.</p> <p>Results</p> <p>The transient rise in intracellular Ca²⁺induced by agonists for FPR1 or FPR2 in human neutrophils occurred also in the presence of a chelator of Ca²⁺(EGTA). PBP10 inhibited not only FPR2-induced oxidase activity, but also the transient rise in intracellular Ca²⁺.</p> <p>Conclusions</p> <p>Ca²⁺signaling mediated <it>via </it>FPR2 follows the same route as FPR1, which involves initial emptying of the intracellular stores. PBP10 inhibits selectively the signals generated by FPR2, both with respect to NADPH-oxidase activity and the transient rise in intracellular Ca²⁺induced by agonist exposure.</p

Intracranial Pressure and Cerebral Perfusion Pressure Monitoring in Non-TBI Patients: Special Considerations

The effect of intracranial pressure (ICP) and the role of ICP monitoring are best studied in traumatic brain injury (TBI). However, a variety of acute neurologic illnesses e.g., subarachnoid hemorrhage, intracerebral hemorrhage, ischemic stroke, meningitis/encephalitis, and select metabolic disorders, e.g., liver failure and malignant, brain tumors can affect ICP. The purpose of this paper is to review the literature about ICP monitoring in conditions other than TBI and to provide recommendations how the technique may be used in patient management. A PubMed search between 1980 and September 2013 identified 989 articles; 225 of which were reviewed in detail. The technique used to monitor ICP in non-TBI conditions is similar to that used in TBI; however, indications for ICP monitoring often are intertwined with the presence of obstructive hydrocephalus and hence the use of ventricular catheters is more frequent. Increased ICP can adversely affect outcome, particularly when it fails to respond to treatment. However, patients with elevated ICP can still have favorable outcomes. Although the influence of ICP-based care on outcome in non-TBI conditions appears less robust than in TBI, monitoring ICP and cerebral perfusion pressure can play a role in guiding therapy in select patients

Intraoperative non invasive intracranial pressure monitoring during pneumoperitoneum: a case report and a review of the published cases and case report series.

Non-invasive measurement of ICP (nICP) can be warranted in patients at risk for developing increased ICP during pneumoperitoneum (PP). Our aim was to assess available data on the application of nICP monitoring during these procedures and to present a patient assessed with an innovative combination of noninvasive tools. Literature review of nICP assessment during PP did not find any studies comparing different methods intraprocedurally and only few studies of any nICP monitoring were available: transcranial Doppler (TCD) studies used the pulsatility index (PI) as an estimator of ICP and failed to detect a significant ICP increase during PP, whereas two out of three optic nerve sheath diameter (ONSD) studies detected a statistically significant ICP increase. In the case study, we describe a 52 year old man with a high grade thalamic glioma who underwent urgent laparoscopic cholecystectomy. Considering the high intraoperative risk of developing intracranial hypertension, he was monitored through parallel ONSD ultrasound measurement and TCD derived formulae (flow velocity diastolic formula, FVdnICP, and PI). ONSD and FVdnICP methods indicated a significant ICP increase during PP, whereas PI was not significantly increased. Our experience, combined with the literature review, seems to suggest that PI might not detect ICP changes in this context, however we indicate a possible interest of nICP monitoring during PP by means of ONSD and of TCD derived FVdNICP, especially for patients at risk for increased ICP.D.C. and M.C. are partially supported by NIHR Brain Injury Healthcare Technology Co-operative, Cambridge, UK