gp91phox-dependent expression of platelet CD40 ligand

Background-CD40 ligand (CD40L) expression on platelets is mediated by agonists, but the underlying mechanism is still unclear. Methods and Results-CD40L expression was measured in platelets from healthy subjects both with and without the addition of antioxidants or a phospholipase A2 (PLA2) inhibitor and in platelets from 2 patients with an inherited deficiency of gp91phox. Immunoprecipitation analysis was also performed to determine whether normal platelets showed gp91phox expression. Unlike catalase and mannitol, superoxide dismutase inhibited agonist-induced platelet CD40L expression in healthy subjects. Immunoprecipitation analysis also showed that platelets from healthy subjects expressed gp91phox. In 2 male patients with inherited gp91phox deficiency, collagen-, thrombin-, and arachidonic acid-stimulated platelets showed an almost complete absence of superoxide anion (O2-) and CD40L expression. Incubation of platelets from healthy subjects with a PLA2 inhibitor almost completely prevented agonist-induced O2- and CD40L expression. Conclusions-These data provide the first evidence that platelet CD40L expression occurs via arachidonic acid-mediated gp91phox activation

Neonatal effects of the administration of meperidine and promethazine to the mother in labor. Double blind study

Peer Reviewe

Vitamin C inhibits platelet expression of CD40 ligand

Upon stimulation with agonists, platelets express CD40 ligand (CD40L), a transmembrane protein implicated in the initiation and progression of atherosclerotic disease. We have recently discovered that oxidative stress plays a major role in platelet CD40L expression. In this study, we sought to determine whether vitamin C, a known antioxidant, is able to influence platelet CD40L expression. In vitro experiments were done by stimulating platelets with collagen in the presence or absence of vitamin C (50-100 mu M) or vehicle as control. An in vivo study was done in 10 healthy subjects who were randomized to intravenous infusion of placebo or 1 g vitamin C for 45 min in a crossover design. At the end of infusion platelet CD40L and O2- were measured. The in vitro study demonstrated that vitamin C dose dependently inhibited platelet CD40L expression without affecting agonist-induced platelet aggregation. In subjects treated with placebo no changes of platelet CD40L and O2- were observed; conversely, vitamin C infusion caused a significant and parallel decrease of platelet O2- (-70%, P < 0.001) and CD40L (-68%, P < 0.001). Platelet aggregation was not modified by either treatment. This study suggests that water-soluble antioxidants, which scavenge superoxide radicals, may reduce platelet CD40L expression. (c) 2005 Elsevier Inc. All rights reserved

Does the Presence of an Iliac Aneurysm Affect Outcome of Endoluminal AAA Repair? An Analysis of 336 Cases

AbstractObjective: to determine whether the presence of an iliac aneurysm compromises outcome of endovascular exclusion of AAA and to ascertain the fate of the iliac aneurysmal sac.Patients and methods: between April 1997 and March 2001, data on 336 consecutive patients undergoing endovascular repair for AAA were entered in a prospective database. Suitability for endovascular repair was assessed by preoperative contrast-enhanced computed tomography. A maximum common iliac artery (CIA) diameter ≥20mm was defined as iliac aneurysm. Patients with and without iliac aneurysms were compared to early (immediate conversion or perioperative death) and late failure (increase in aneurysm diameter or persisting graft-related endoleak, or late AAA rupture or conversion).Results: fifty-nine patients (18%) had iliac aneurysms, 19 were bilateral, for a total of 78 aneurysmal iliac arteries (median diameter 23mm; range 20–50mm). A distal seal was achieved by landing in 33 external iliac arteries, in 20 ectatic CIAs, and in 25 normal CIAs. Operating time differed significantly between patients with and without CIA aneurysms (153±71 vs 123±55min,p =0.0001), whereas no statistically significant differences were found with respect to early and late failure (2% vs 3%, p=0.5 and 14% vs 8%, p=0.11, respectively). There were no cases of buttock or colon necrosis. At a median follow-up of 14 months (range 0–46; i.q.r. 7–27 months) common iliac diameter decreased ≥2mm in 49 cases, remained stable in 25, and increased ≥2mm in 3.Conclusion: the presence of iliac aneurysm rendered endoluminal AAA repair more complex but did not affect feasibility and long-term outcome of the procedure. In our experience internal iliac exclusion was never associated with significant morbidity. These data may be useful when considering endovascular repair in high-risk patients with challenging anatomy

Stigmatisation and resilience in inflammatory bowel disease

© 2019, The Author(s). Inflammatory bowel disease, which includes Crohn’s disease and ulcerative colitis, is an immune-mediated, chronic relapsing disorder characterised by severe gastrointestinal symptoms that dramatically impair patients’ quality of life, affecting psychological, physical, sexual, and social functions. As a consequence, patients suffering from this condition may perceive social stigmatisation, which is the identification of negative attributes that distinguish a person as different and worthy of separation from the group. Stigmatisation has been widely studied in different chronic conditions, especially in mental illnesses and HIV-infected patients. There is a growing interest also for patients with inflammatory bowel disease, in which the possibility of disease flare and surgery-related issues seem to be the most important factors determining stigmatisation. Conversely, resilience represents the quality that allows one to adopt a positive attitude and good adjustments despite adverse life events. Likewise, resilience has been studied in different populations, age groups, and chronic conditions, especially mental illnesses and cancer, but little is known about this issue in patients with inflammatory bowel disease, even if this could be an interesting area of research. Resilience can be strengthened through dedicated interventions that could potentially improve the ability to cope with the disease. In this paper, we focus on the current knowledge of stigmatisation and resilience in patients with inflammatory bowel disease

Oxidative stress-mediated platelet CD40 ligand upregulation in patients with hypercholesterolemia: effect of atorvastatin

Objectives: We speculated that in patients with hypercholesterolemia CD40L overexpression could depend on low-density lipoprotein (LDL)-induced enhanced intraplatelet formation of O-2(.-) and statin could reduce platelet CD40L via interference with platelet O-2(.-) production. Background: CD40L is a protein with inflammatory and thrombotic properties. CD40L is upregulated in platelets from hypercholesterolemic (HC) patients but the underlying mechanism is unclear. Methods: Collagen-induced platelet CD40L and platelet O-2(.-) expression were investigated in 40 HC patients and 40 healthy subjects. HC patients were then randomized to either a diet (n = 20) (group A) or atorvastatin 10 mg day (n = 20) (group B); the above variables were measured at baseline and after 3 and 30 days of treatment. O-2(.-) and CD40L were also measured in vitro in LDL-treated platelets with or without nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor or atorvastatin added. Results: Compared with controls, HC patients showed higher values of platelet CD40L (P < 0.001) and O-2(.-) (P < 0.001). Platelet CD40L was significantly correlated with O-2(.-) (P < 0.001). The interventional trial showed no changes in group A and a significant and parallel decrease in platelet CD40L (P < 0.001) and O-2(.-) (P < 0.001) in group B. In vitro studies demonstrated that LDL-induced platelet CD40L and GP IIb/IIIa (PAC1 binding) activation via the NADPH oxidase pathway. CD40L upregulation was counteracted by atorvastatin in a dose-dependent fashion. Conclusions: This study suggests that in patients with hypercholesterolemia platelet CD40L is upregulated via NADPH oxidase-dependent O-2(.-) generation. Atorvastatin downregulated CD40L with an oxidative stress-mediated mechanism likely involving platelet NADPH oxidase, an effect that seemed to be independent of its cholesterol-lowering action

Short-term treatment with atorvastatin reduces platelet CD40 ligand and thrombin generation in hypercholesterolemic patients

Background - Soluble CD40L (sCD40L), a substance that maximally reflects in vivo platelet activation, is increased in patients with hypercholesterolemia. We investigated the relation between sCD40L and platelet CD4OL in hypercholesterolemic patients before and after a short-term treatment with atorvastatin. Methods and Results - Collagen-induced platelet CD40L and plasma levels of sCD40L and prothrombin fragment F1+2, a marker of thrombin generation, were investigated in 30 hypercholesterolemic patients and 20 healthy subjects. Hypercholesterolemic patients were then randomized to either diet ( n = 15; group A) or atorvastatin 10 mg/d ( group B); the aforementioned variables were measured at baseline and after 3 days of treatment. Compared with referents, hypercholesterolemic patients showed higher values of platelet CD40L ( P < 0.005), sCD40L ( P < 0.005), and F1 + 2 ( P < 0.003). Platelet CD40L was significantly correlated with sCD40L ( P < 0.001), and the latter was significantly correlated with F1 + 2 ( P < 0.001). The intervention trial showed no changes in group A but a significant decrease in platelet CD40L ( P < 0.01), sCD40L ( P < 0.002), and F1 + 2 ( P < 0.03) in group B. In vitro studies demonstrated that cholesterol enhanced platelet CD40L and CD40L-mediated clotting activation by human monocytes; also, atorvastatin dose-dependently inhibited platelet CD40L expression and clotting activation by CD40L-stimulated monocytes. Conclusions - This study shows that, in hypercholesterolemia, platelet overexpression of CD40L may account for enhanced plasma levels of sCD40L and F1 + 2. Atorvastatin exerts a direct antithrombotic effect via inhibition of platelet CD40L and CD40L-mediated thrombin generation, independently of its cholesterol-lowering effect

The on-ground calibration of the flight model of the HPGSPC onboard the SAX satellite: Calibration set-up and preliminary results

The High Pressure Gas Scintillation Proportional Counter (HPGSPC) is one of the Narrow Field Instruments of the Italian-Dutch X-ray astronomy satellite SAX. Sensitive in the hard X-ray band (4–120 keV), with a very good energy resolution, the HPGSPC is well suited for studying in detail the cyclotron features present in the hard X-ray spectrum of some celestial sources. The scientific calibration of the flight model of the HPGSPC took place at the LABEN premises(Vimodrone-Milano) during October and November 1994. In this paper we briefly describe the on-ground instrument calibration system and we report some preliminary results that show the performances of both single/double event and position reconstruction/energy correction onboard processing. Preliminary results concerning the energy resolution and energy linearity are reported too

Inherited human gp91phox deficiency is associated with impaired isoprostane formation and platelet dysfunction

Platelet isoprostane 8-ISO-prostaglandin F2α (8-iso-PGF2α), a proaggregating molecule, is believed to derive from nonenzymatic oxidation of arachidonic acid. We hypothesized that NADPH is implicated in isoprostane formation and platelet activation