Platelets modulate the proteolysis of factor VIII:C protein by plasmin

Factor VIII coagulant protein (VIII:C) functions as a critical cofactor with factor IXa, calcium ions, and phospholipid during the activation of factor X. In the course of this reaction, the activity of VIII:C is first increased and then is destroyed by one or more serine proteases that are part of the coagulation sequence. In this study, we have investigated the influence of platelets on the inactivation of VIII:C by plasmin. Platelets were separated from plasma proteins in the presence of granule release inhibitors and were incubated with plasmin and isolated VIII:C or the complex of purified VIII:C/von Willebrand factor (vWF); VIII:C activity and antigen levels were assessed over time. In the presence of platelets, the isolated VIII:C showed an initial increase in VIII:C activity that was not present when platelets were absent, and the VIII:C/vWF showed an increase in VIII:C activity over that seen when platelets were absent. In addition, platelets stabilized VIII:C activity over a one-hour time course when compared with buffer. The VIII:C antigen did not increase and decreased slowly whether platelets were present or absent. Preincubating the platelets with ristocetin, collagen, or plasmin did not alter the results, and experiments using platelets from a patient with severe von Willebrand's disease also showed a pattern similar to that seen with normal platelets. Experiments using fixed platelets or phospholipid vesicles showed that they did not support the activation reaction or delay the inactivation reaction. These studies demonstrate that platelets modulate the activation and inactivation of VIII:C by plasmin, apparently by a mechanism that is independent of the platelet release reaction.     

Effect of cobalt addition on the corrosion behavior of near equiatomic NiTi shape memory alloy in normal saline solution: electrochemical and XPS studies

The electrochemical and corrosion (uniform and localized) behavior of a binary Ni₅₂Ti₄₈ shape memory alloy (SMA) and two ternary Ni₅₂Ti_48−xCo_x (x = 1.5 and 4.0 wt%) SMAs were studied. Measurements were conducted in 0.9% NaCl solution at 37 °C employing various electrochemical methods. These include: linear polarization resistance (LPR), linear sweep voltammetry (LSV), chronoamperometry and dynamic electrochemical impedance spectroscopy (DEIS). Such measurements were complemented with scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) analysis. Results revealed that the addition of alloyed Co to NiTi significantly reduced the uniform corrosion rate of the studied SMA and greatly enhanced its pitting corrosion resistance. XPS measurements evidenced high stability of the passive layer and limited adsorption of chloride ions. Additionally, it was found that the passive layer remained primarily composed of titanium oxides. Microstructure changes accompanying the addition of Co were also used to account for its role in improving the corrosion resistance of these materials.

The electrochemical and corrosion (uniform and localized) behavior of a binary Ni₅₂Ti₄₈ shape memory alloy (SMA) and two ternary Ni₅₂Ti_48−xCo_x (x = 1.5 and 4.0 wt%) SMAs were studied.     

Care planning for long‐term conditions – a concept mapping

Objective

This article focuses on approaches within clinical practice that seek to actively involve patients with long‐term conditions (LTCs) and how professionals may understand and implement them. Personalized care planning is one such approach, but its current lack of conceptual clarity might have impeded its widespread implementation to date. A variety of overlapping concepts coexist in the literature, which have the potential to impair both clinical and research agendas. The aim of this article is therefore to explore the meaning of the concept of care planning in relation to other overlapping concepts and how this translates into clinical practice implementation.

Methods

Searches were conducted in the Cochrane database for systematic reviews, CINHAL and MEDLINE. A staged approach to conducting the concept mapping was undertaken, by (i) an examination of the literature on care planning in LTCs; (ii) identification of related terms; (iii) locating reviews of those terms. Retrieved articles were subjected to a content analysis, which formed the basis of our concept maps. (iv) We then appraised these against knowledge and experience of the implementation of care planning in clinical practice.

Results and Conclusions

Thirteen articles were retrieved, in which the core importance of patient‐centredness, shared decision making and self‐management was highlighted. Literature searches on these terms retrieved a further 24 articles. Our concept mapping exercise shows that whilst there are common themes across the concepts, the differences between them reflect the context and intended outcomes within clinical practice. We argue that this clarification exercise will allow for further development of both research and clinical implementation agendas.     

Immediate effect of percutaneous myocardial laser revascularization on hemodynamics and left ventricular systolic function in severe angina pectoris

Experimental data suggest that myocardial revascularization with a high-energy laser may cause a significant reduction in left ventricular (LV) function immediately after creation of myocardial channels. We sought to determine if percutaneous myocardial laser revascularization (PMR) causes immediate deterioration in hemodynamic parameters or regional LV systolic function. PMR was performed in 40 patients (mean age 62.9 +/- 10.8 years) using the Eclipse Holmium laser (26 had PMR alone; 14 patients underwent PMR plus percutaneous coronary intervention). Intracardiac pressures and left ventriculograms were recorded before and after PMR. Regional wall motion was assessed using the centerline method. A mean of 18 +/- 5 channels were created per patient. There was no significant change in LV ejection fraction immediately after PMR (56 +/- 9% vs 55 +/- 10%, p = 0.25). No deterioration in regional wall motion was demonstrated in the lased region (mean chord motion for anterior wall PMR: -1.5 +/- 0.8 before vs -1.5 +/- 0.8 after the procedure, p = 0.93; inferior wall PMR: -1.5 +/- 0.9 before vs - 1.6 +/- 0.8 after the procedure, p = 0.43). Similarly, there was no change in the number of hypokinetic chords in the treated region. Systemic blood pressure, LV end-diastolic pressure, heart rate, and right-sided heart pressures were not significantly different after laser revascularization. In patients with refractory angina, PMR did not cause immediate deterioration in hemodynamic status or regional LV function.     

Identification of an oncogenic form of the thrombopoietin receptor MPL using retrovirus-mediated gene transfer

Thrombopoietin and its receptor (MPL) are important regulators of megakaryopoiesis. We have identified an activating mutation of MPL using a combination of a retrovirus-mediated gene transfer and polymerase chain reaction-driven random mutagenesis. This point mutation causes a single amino acid substitution from Ser498 to Asn498 in the transmembrane region and abrogates factor-dependency of all interleukin-3-dependent cell lines tested. Murine interleukin-3- dependent Ba/F3 cells expressing the mutated but not the normal form of MPL were tumorigenic when transduced into syngeneic mice. Analysis of intracellular signaling pathways indicated that the mutant MPL protein constitutively activated two distinct signaling pathways, SHC-Raf-MAPK and JAK2-STAT3/STAT5.