Klipsun Magazine, 1973, Volume 03, Issue 02

https://cedar.wwu.edu/klipsun_magazine/1010/thumbnail.jp

Klipsun Magazine, 1972, Volume 03, Issue 01

https://cedar.wwu.edu/klipsun_magazine/1009/thumbnail.jp

COVID-19 has disrupted businesses’ ability to prepare for Brexit, but the lack of clarity on the UK-EU relationship is worse

Almost half of businesses report that COVID-19 has negatively affected their ability to prepare for Brexit. More than half listed uncertainty on the future arrangements between the UK and EU as a limitation on their ability to prepare for Brexit. This is higher than the proportion who listed COVID-19 as a limiting factor and far higher than any other factor. Furthermore, over 80 per cent of businesses are concerned about the implications of the Transition Period ending on 1st January 2021. Josh De Lyon, Swati Dhingra, and Edoardo Tolva (LSE) argue that COVID-19 has significantly disrupted businesses’ ability to prepare for Brexit but the greatest constraint on preparation has been the lack of clarity on the UK’s future relationship with the EU

A successful experimental model for intimal hyperplasia prevention using a resveratrol eluting balloon

Objective: Restenosis due to intimal hyperplasia is a major clinical problem that compromises the success of angioplasty and endovascular surgery. Resveratrol (RSV) has demonstrated a beneficial effect on restenosis from angioplasty. Unfortunately, the physicochemical characteristics of RSV reduce the practicality of its immediate clinical application. This work proposes an experimental model aiming to setup an intravessel, elutable, RSV-containing compound. Methods: A 140 mg/mL RSV sterile injectable solution with a suitable viscosity for intravascular administration by drugdelivery catheter (RSV-c) was prepared. This solution was locally administered in the common iliac artery of adult male New Zealand White rabbits using a dedicated device (Genie; Acrostak, Geneva, Switzerland) after the induction of intimal hyperplasia by traumatic angioplasty. The RSV concentrations in the wall artery were determined, and the thickness of the harvested iliac arteries was measured over a 1-month period. Results: The Genie catheter was applied in rabbit vessels, and the local delivery resulted in an effective reduction in restenosis after plain angioplasty. Notably, RSV-c forced into the artery wall by balloon expansion might accumulate in the interstitial areas or within cells, avoiding the washout of solutions. Magnification micrographs showed intimal proliferation was significantly inhibited when RSV-c was applied. Moreover, no adverse events were documented in in vitro or in vivo studies. Conclusions: RSV can be advantageously administered in the arterial walls by a drug-delivery catheter to reduce the risk of restenosis

Do Women Have a Higher Risk of Adverse Events after Carotid Revascularization?

Carotid artery stenosis is thought to cause up to 10% of ischemic strokes. Till now, the optimal treatment between carotid endarterectomy (CEA) and carotid artery stenting (CAS) remains debated, in particular for specific subgroups of patients. Available data suggest that female have higher risk of perioperative adverse events, but conflicting results comparing CEA and CAS regarding the benefit for male or female are present in the literature. A systematic review of recent publications on gender-related differences in operative risks is reported. Moreover, a consecutive cohort of 912 symptomatic and asymptomatic patients undergoing CEA (407, 44.6%) or CAS (505, 55.4%) in a single institution has been evaluated to determine the influence of gender (59.7% male vs. 40.3% female) on the outcomes after both revascularization procedures at 30 days and during 3 years of follow-up. Our experience seems to confirm literature data as regarding female higher risk of restenosis. Female patients had higher periprocedural (2.7% female vs. 0.9% male; p < 0.05) and long-term (11.4% female vs. 4.6% male; p < 0.05) restenosis rate. In conclusion, female anatomic and pathologic parameters should be taken into account for an accurate diagnosis of carotid stenosis and guidelines should be adjusted consequently

Soluble HLA-DR serum levels are associated with smoking but not with acute coronary syndrome

Peer reviewe

High relative amount of nodular calcification in femoral plaques is associated with milder lower extremity arterial disease.

Peer reviewe

Plasminogen activator-coated nanobubbles targeting cell-bound β2-glycoprotein I as a novel thrombus-specific thrombolytic strategy

Beta2-glycoprotein I (β2-GPI) is a serum protein widely recognized as the main target of antibodies present in patients with anti-phospholipid syndrome (APS). β2-GPI binds to activated endothelial cells, platelets and leukocytes, key players in thrombus formation. We developed a new targeted thrombolytic agent consisting of nanobubbles (NBs) coated with recombinant tissue plasminogen activator (rtPA) and recombinant antibody specific for cell-bound β2-GPI. The therapeutic efficacy of targeted nanobubbles was evaluated in vitro, using platelet-rich blood clots, and in vivo in three different animal models: 1) thrombosis developed in a rat model of APS; 2) ferric chloride-induced mesenteric thrombosis in rats, and 3) thrombotic microangiopathy in a mouse model of atypical hemolytic uremic syndrome (C3-gain-of-function mice). Targeted nanobubbles bound preferentially to platelets and leukocytes within thrombi and to endothelial cells through β2-GPI expressed on activated cells. In vitro, rtPA-targeted NBs (rtPA-tNBs) induced greater lysis of platelet-rich blood clots than untargeted NBs. In a rat model of APS, administration of rtPA-tNBs caused rapid dissolution of thrombi and, unlike soluble rtPA that induced transient thrombolysis, prevented new thrombus formation. In a rat model of ferric chloride triggered thrombosis, rtPA-tNBs, but not untargeted NBs and free rtPA, induced rapid and persistent recanalization of occluded vessels. Finally, treatment of C3-gain-of-function mice with rtPA-tNBs, that target β2-GPI deposited in kidney glomeruli, decreased fibrin deposition, and improved urinalysis data with a greater efficiency than untargeted NBs. Our findings suggest that targeting cell-bound β2-GPI may represent an efficient and thrombus-specific thrombolytic strategy in both APS-related and APSunrelated thrombotic conditions

Alterations of Cardiac Protein Kinases in Cyclic Nucleotide-Dependent Signaling Pathways in Human Ischemic Heart Failure

ObjectivesImpaired protein kinase signaling is a hallmark of ischemic heart disease (IHD). Inadequate understanding of the pathological mechanisms limits the development of therapeutic approaches. We aimed to identify the key cardiac kinases and signaling pathways in patients with IHD with an effort to discover potential therapeutic strategies.MethodsCardiac kinase activity in IHD left ventricle (LV) and the related signaling pathways were investigated by kinomics, transcriptomics, proteomics, and integrated multi-omics approach.ResultsProtein kinase A (PKA) and protein kinase G (PKG) ranked on top in the activity shift among the cardiac kinases. In the IHD LVs, PKA activity decreased markedly compared with that of controls (62% reduction, p = 0.0034), whereas PKG activity remained stable, although the amount of PKG protein increased remarkably (65%, p = 0.003). mRNA levels of adenylate cyclases (ADCY 1, 3, 5, 9) and cAMP-hydrolysing phosphodiesterases (PDE4A, PDE4D) decreased significantly, although no statistically significant alterations were observed in that of PKGs (PRKG1 and PRKG2) and guanylate cyclases (GUCYs). The gene expression of natriuretic peptide CNP decreased remarkably, whereas those of BNP, ANP, and neprilysin increased significantly in the IHD LVs. Proteomics analysis revealed a significant reduction in protein levels of “Energy metabolism” and “Muscle contraction” in the patients. Multi-omics integration highlighted intracellular signaling by second messengers as the top enriched Reactome pathway.ConclusionThe deficiency in cAMP/PKA signaling pathway is strongly implicated in the pathogenesis of IHD. Natriuretic peptide CNP could be a potential therapeutic target for the modulation of cGMP/PKG signaling.Peer reviewe