Abstract Von Willebrand factor (VWF) is a large multimeric glycoprotein produced in endothelial cells and megakaryocytes and present in subendothelial matrix, blood plasma and platelets. VWF mediates ...adhesion and aggregation of platelets at sites of vascular injury, processes that are critical for both haemostasis and thrombosis. Thrombus formation involves complex events that are influenced by different environmental conditions. Progress in understanding the structure and function of VWF and the mechanisms that underlie its interactions with platelets has led to important insight into the differentiation between normal haemostasis and pathological arterial thrombosis. The conventional view of signalling-induced platelet aggregation has recently been extended to include activation-independent aggregation. A novel mechanism has been demonstrated for initiating thrombus formation under high haemodynamic forces that involves αIIb β3 -independent platelet aggregation at the interface between immobilised and soluble VWF. This VWF-mediated process may be a key determinant of platelet accumulation in stenotic arteries leading to acute thrombotic occlusion.
Platelet-adhesive mechanisms play a well-defined role in hemostasis and thrombosis, but evidence continues to emerge for a relevant contribution to other pathophysiological processes, including ...inflammation, immune-mediated responses to microbial and viral pathogens, and cancer metastasis. Hemostasis and thrombosis are related aspects of the response to vascular injury, but the former protects from bleeding after trauma, while the latter is a disease mechanism. In either situation, adhesive interactions mediated by specific membrane receptors support the initial attachment of single platelets to cellular and extracellular matrix constituents of the vessel wall and tissues. In the subsequent steps of thrombus growth and stabilization, adhesive interactions mediate platelet-to-platelet cohesion (i.e., aggregation) and anchoring to the fibrin clot. A key functional aspect of platelets is their ability to circulate in a quiescent state surveying the integrity of the inner vascular surface, coupled to a prompt reaction wherever alterations are detected. In many respects, therefore, platelet adhesion to vascular wall structures, to one another, or to other blood cells are facets of the same fundamental biological process. The adaptation of platelet-adhesive functions to the effects of blood flow is the main focus of this review.
We develop an experimental protocol to quantify the speciation of Cu ions (ZCuIIOH and Z2CuII) in Cu-CHA catalysts for the NH3 Selective Catalytic Reduction of NOx (NH3-SCR). Toward this end, we ...performed four transient tests, namely H2-TPR, NO + NH3 TPR, NO2 adsorption + TPD, and NH3 adsorption + TPD, over two sets of Cu-CHA research catalysts characterized by different Cu contents (0–2.1% w/w) and SiO2/Al2O3 (SAR) ratios (10–25). Preliminary H2-TPR tests on the samples with the extreme SAR and Cu loading values were used to identify the variability range of the fractions of ZCuIIOH and Z2CuII species in these catalysts. The ZCuIIOH fraction was found to vary between 0.55 (at Cu/Al = 0.11) and 0.79 (at Cu/Al = 0.29). NO+NH3 TPR runs demonstrated that the NO + NH3 mixture is a much stronger reducing agent than H2: full reduction of all the Cu was obtained already at lower temperature, and differences in the reducibility of ZCuIIOH and Z2CuII were strongly attenuated. Both the integral NO consumption and the integral N2 release were found to be effective estimators of the reducible Cu in Cu-CHA, matching the total Cu from ICP measurements. NO2 adsorption + TPD tests pointed out that NO2 is adsorbed in the form of nitrates on ZCuIIOH ions only, the nitrates storage capacity being therefore dependent on SAR and Cu loading: on increasing both parameters, the amount of stored NO x increased, as well as their stability. Both the NO released during isothermal NO2 adsorption and the NO2 released during the following TPD can be used to directly estimate the number of ZCuIIOH ions in Cu-CHA. Finally, NH3-TPD provided information on the acid sites in the Cu-CHA samples. From the NH3 stored on Lewis sites, it was possible to evaluate the number of NH3 molecules coordinated to each Cu atom: a decrease of the NH3/Cu ratio on increasing both SAR and Cu content was observed. This behavior is explained by the changes in the distribution of ZCuIIOH and Z2CuII sites in Cu-CHA, as a result of varying the Cu/Al ratio. In accordance with literature results, we found that Cu ions are able to ligate either 3 (ZCuIIOH) or 4 (Z2CuII) NH3 molecules, when gaseous NH3 is present, the NH3/Cu ratios estimated from our experiments falling close to this range. When only preadsorbed NH3 was present, however, (no gaseous ammonia), the NH3/Cu ratio dropped to either 1 (ZCuIIOH) or 2 (Z2CuII). On the basis of these elements, NH3 TPD can also be used to quantify the two Cu species in Cu-CHA. We recommend however the more straightforward approach based on (i) NO + NH3 TPR (for direct quantification of the overall reducible Cu) and (ii) NO2 TPD (for direct quantification of the ZCuIIOH species).
Thermal inkjet printing technology has been applied successfully to cell printing. However, there are concerns that printing process may cause cell damages or death. We conducted a comprehensive ...study of thermal inkjet printed Chinese hamster ovary (CHO) cells by evaluating cell viability and apoptosis, and possible cell membrane damages. Additionally, we studied the cell concentration of bio-ink and found optimum printing of concentrations around 8 million cells per mL. Printed cell viability was 89% and only 3.5% apoptotic cells were observed after printing. Transient pores were developed in the cell membrane of printed cells. Cells were able to repair these pores within 2 h after printing. Green fluorescent protein (GFP) DNA plasmids were delivered to CHO-S cells by co-printing. The transfection efficiency is above 30%. We conclude that thermal inkjet printing technology can be used for precise cell seeding with minor effects and damages to the printed mammalian cells. The printing process causes transient pores in cell membranes, a process which has promising applications for gene and macroparticles delivery to induce the biocompatibility or growth of engineered tissues. Biotechnol. Bioeng. 2010;106: 963-969.
Adhesion mechanisms in platelet function Ruggeri, Zaverio M; Mendolicchio, G Loredana
Circulation research,
2007-June-22, Volume:
100, Issue:
12
Journal Article
Peer reviewed
Open access
Platelet adhesion is an essential function in response to vascular injury and is generally viewed as the first step during which single platelets bind through specific membrane receptors to cellular ...and extracellular matrix constituents of the vessel wall and tissues. This response initiates thrombus formation that arrests hemorrhage and permits wound healing. Pathological conditions that cause vascular alterations and blood flow disturbances may turn this beneficial process into a disease mechanism that results in arterial occlusion, most frequently in atherosclerotic vessels of the heart and brain. Besides their relevant role in hemostasis and thrombosis, platelet adhesive properties are central to a variety of pathophysiological processes that extend from inflammation to immune-mediated host defense and pathogenic mechanisms as well as cancer metastasis. All of these activities depend on the ability of platelets to circulate in blood as sentinels of vascular integrity, adhere where alterations are detected, and signal the abnormality to other platelets and blood cells. In this respect, therefore, platelet adhesion to vascular wall structures, to one another (aggregation), or to other blood cells, represent different aspects of the same fundamental biological process. Detailed studies by many investigators over the past several years have been aimed to dissect the complexity of these functions, and the results obtained now permit an attempt to integrate all the available information into a picture that highlights the balanced diversity and synergy of distinct platelet adhesive interactions.
Migraine is a primary headache which World Health Organization ranks in 19th place in the list of disabling diseases. In Europe, in 2004, the total costs for migraine were quantified by Stovner and ...Berg, Eur J Neurol, 12(s1) (
2005
) at €27 billion. The objective of this study is to provide an estimate of the incremental cost-effectiveness ratio (ICER) of the treatment of chronic migraine with Botox compared to treatment with placebo in the perspective of the Italian National Health Service and society. To do this we studied the disease progression in a cohort of 688 individuals (patients enrolled in the study PREEMPT) via the application of a Markov model. Over a period of 2 years, the total costs of the experimental arm of the model amounted to €3,274 compared with a gain of 1.34 QALYs. In contrast, the costs of the control arm amounted to €2,395 with a gain of 1.24 QALYs. It follows that the incremental costs amounted to €889 compared to an incremental gain of 0.09 QALYs in favor of the experimental arm. The relationship between costs and incremental QALYs generated an ICER of €9,407/QALY. The incremental cost-effectiveness ratio, therefore, is favorable compared to the value usually considered by NICE as a threshold limit for reimbursement which ranges between €20,000 and €40,000/QALY.
Multicellular interactions of platelets, leukocytes, and the blood vessel wall support coagulation and precipitate arterial and venous thrombosis. High levels of angiotensin II cause arterial ...hypertension by a complex vascular inflammatory pathway that requires leukocyte recruitment and reactive oxygen species production and is followed by vascular dysfunction. We delineate a previously undescribed, proinflammatory coagulation-vascular circuit that is a major regulator of vascular tone, blood pressure, and endothelial function. In mice with angiotensin II-induced hypertension, tissue factor was up-regulated, as was thrombin-dependent endothelial cell vascular cellular adhesion molecule 1 expression and integrin α
β
- and platelet-dependent leukocyte adhesion to arterial vessels. The resulting vascular inflammation and dysfunction was mediated by activation of thrombin-driven factor XI (FXI) feedback, independent of factor XII. The FXI receptor glycoprotein Ibα on platelets was required for this thrombin feedback activation in angiotensin II-infused mice. Inhibition of FXI synthesis with an antisense oligonucleotide was sufficient to prevent thrombin propagation on platelets, vascular leukocyte infiltration, angiotensin II-induced endothelial dysfunction, and arterial hypertension in mice and rats. Antisense oligonucleotide against FXI also reduced the increased blood pressure and attenuated vascular and kidney dysfunction in rats with established arterial hypertension. Further, platelet-localized thrombin generation was amplified in an FXI-dependent manner in patients with uncontrolled arterial hypertension, suggesting that platelet-localized thrombin generation may serve as an inflammatory marker of high blood pressure. Our results outline a coagulation-inflammation circuit that promotes vascular dysfunction, and highlight the possible utility of FXI-targeted anticoagulants in treating hypertension, beyond their application as antithrombotic agents in cardiovascular disease.
Chronic infection with hepatitis B virus (HBV) is a major risk factor for the development of hepatocellular carcinoma (HCC). The pathogenesis of HBV-associated HCC involves both viral and host ...factors. The latter include a functionally inefficient CD8 ⁺ T-cell response that fails to clear the infection from the liver but sustains a chronic necroinflammatory process that contributes to the development of HCC. According to this scenario, amelioration of immune-mediated chronic liver injury may prevent HCC. Because platelets facilitate immune-mediated liver injury by promoting the hepatic accumulation of virus-specific CD8 ⁺ T cells, we evaluated the long-term consequences of antiplatelet therapy in an HBV transgenic mouse model of chronic immune-mediated necroinflammatory liver disease that progresses to HCC. Treatment with aspirin and clopidogrel during the chronic phase of the disease diminished the number of intrahepatic HBV-specific CD8 ⁺ T cells and HBV-nonspecific inflammatory cells, the severity of liver fibrosis, and the development of HCC. Antiplatelet therapy improved overall survival without causing significant side effects. In contrast, the same antiplatelet regimen had no antitumor effect when HCC was induced nonimmunologically by chronic exposure to a hepatotoxic chemical. The unprecedented observation that antiplatelet therapy inhibits or delays immune-mediated hepatocarcinogenesis suggests that platelets may be key players in the pathogenesis of HBV-associated liver cancer and supports the notion that immune-mediated necroinflammatory reactions are an important cause of hepatocellular transformation during chronic hepatitis.
Healthcare workers exposed to coronavirus 2019 (COVID-19) patients could be psychologically distressed. This study aims to assess the magnitude of psychological distress and associated factors among ...hospital staff during the COVID-19 pandemic in a large tertiary hospital located in north-east Italy.
All healthcare and administrative staff working in the Verona University Hospital (Veneto, Italy) during the COVID-19 pandemic were asked to complete a web-based survey from 21 April to 6 May 2020. Symptoms of post-traumatic distress, anxiety and depression were assessed, respectively, using the Impact of Event Scale (IES-R), the Self-rating Anxiety Scale (SAS) and the Patient Health Questionnaire (PHQ-9). Personal socio-demographic information and job characteristics were also collected, including gender, age, living condition, having pre-existing psychological problems, occupation, length of working experience, hospital unit (ICUs and sub-intensive COVID-19 units vs. non-COVID-19 units). A multivariable logistic regression analysis was performed to identify factors associated with each of the three mental health outcomes.
A total of 2195 healthcare workers (36.9% of the overall hospital staff) participated in the study. Of the participants, 35.7% were nurses, 24.3% other healthcare staff, 16.4% residents, 13.9% physicians and 9.7% administrative staff. Nine per cent of healthcare staff worked in ICUs, 8% in sub-intensive COVID-19 units and 7.6% in other front-line services, while the remaining staff worked in hospital units not directly engaged with COVID-19 patients. Overall, 63.2% of participants reported COVID-related traumatic experiences at work and 53.8% (95% CI 51.0%-56.6%) showed symptoms of post-traumatic distress; moreover, 50.1% (95% CI 47.9%-52.3%) showed symptoms of clinically relevant anxiety and 26.6% (95% CI 24.7%-28.5%) symptoms of at least moderate depression. Multivariable logistic regressions showed that women, nurses, healthcare workers directly engaged with COVID-19 patients and those with pre-existing psychological problems were at increased risk of psychopathological consequences of the pandemic.
The psychological impact of the COVID-19 pandemic on healthcare staff working in a highly burdened geographical of north-east Italy is relevant and to some extent greater than that reported in China. The study provides solid grounds to elaborate and implement interventions pertaining to psychology and occupational health.
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