The platelet receptors, glycoprotein VI (GPVI) and integrin α2β1 jointly control collagen-dependent thrombus formation via protein tyrosine kinases. It is unresolved to which extent the ITIM (immunoreceptor tyrosine-based inhibitory motif) receptor PECAM1 and its downstream acting protein tyrosine phosphatase PTPN11 interfere in this process. Here, we hypothesized that integrin α2β1 has a co-regulatory role in the PECAM1- and PTPN11-dependent restraint of thrombus formation. We investigated platelet activation under flow on collagens with a different GPVI dependency and using integrin α2β1 blockage. Blood was obtained from healthy subjects and from patients with Noonan syndrome with a gain-of-function mutation of PTPN11 and variable bleeding phenotype. On collagens with decreasing GPVI activity (types I, III, IV), the surface-dependent inhibition of PECAM1 did not alter thrombus parameters using control blood. Blockage of α2β1 generally reduced thrombus parameters, most effectively on collagen IV. Strikingly, simultaneous inhibition of PECAM1 and α2β1 led to a restoration of thrombus formation, indicating that the suppressing signaling effect of PECAM1 is masked by the platelet-adhesive receptor α2β1. Blood from 4 out of 6 Noonan patients showed subnormal thrombus formation on collagen IV. In these patients, effects of α2β1 blockage were counterbalanced by PECAM1 inhibition to a normal phenotype. In summary, we conclude that the suppression of GPVI-dependent thrombus formation by either PECAM1 or a gain-of-function of PTPN11 can be overruled by α2β1 engagement.
We describe a case of orbital cellulitis with abscess formation following eyebrow piercing complicated by internal jugular vein thrombosis and subretinal abscesses requiring enucleation with orbital abscess drainage. The popularity of body piercing is increasing and physicians should be familiar with the possibility and management of vision-threatening complications of facial piercing. Following left eyebrow piercing, a 20-year-old female experienced increasing periorbital swelling, erythema, chemosis, orbital pain, decreased vision, and concomitant fever, chills, and rhinorrhea.
Laparoscopic cholecystectomy is the preferred method for treating acute cholecystitis. Although the incidence of postoperative infections in laparoscopic cholecystectomy is low, serious postoperative surgical site infections are still reported. Hepatic abscesses, particularly fungal, can occur post-cholecystectomy leading to significant mortality and morbidity.
Atherosclerosis and its associated cardio-cerebrovascular complications remain the leading causes of mortality worldwide. Current lipid-lowering therapies reduce only approximately one-third of the cardiovascular risk. Furthermore, vascular restenosis and thrombotic events following surgical interventions for severe vascular stenosis significantly contribute to treatment failure.
Introduction: Since mechanical thrombectomy has allowed ischemic stroke thrombi retrieval, its exhaustive study has involved a better knowledge of physiopathological processes implied in its formation.
Development: Thrombotic pathways involved in the different vascular beds shared common mechanisms conditioning difficulties in the identification of specific patterns associated with stroke etiology. Other factors as clot formation time, associated inflammatory status or activation of additional immune and coagulation pathways [Neutrophil extracellular traps (NETs) delivery, platelet aggregation, endothelial activation and VonWillebrand Factor release] have been described as determinants in thrombus characteristics.
Objective: Aim: To summarise what is known about the inflammatory nature of atherosclerosis to date.
Patients And Methods: Materials and Methods: We conducted the search using Google Scholar and Medline and selected state-of-the-art articles that were consistent with the aim of study.
Conclusion: Conclusions: To date, there is sufficient evidence that atherosclerosis is driven by the inflammatory process.
