Determinants of ST-segment elevation myocardial infarction as clinical presentation of acute coronary syndrome

Journal of Thrombosis and Thrombolysis - Antiplatelet agents and statin therapies are widely used in patients with known cardiovascular disease. Plaque rupture (PR) and plaque erosion (PE) are the...     

Neointimal proliferation around malapposed struts of a sirolimus-eluting stent: optical coherence tomography findings

A 65-year-old man with hypercholesterolaemia and hypertensionunderwent elective percutaneous coronary intervention (PCI)because of exertional angina. Three sirolimus-eluting stents(Cypher; 3.0     

Dab1‐mediated colocalization of multi‐adaptor protein CIN85 with Reelin receptors,ApoER2 and VLDLR,in neurons

Reelin‐Dab1 signaling is indispensable for proper positioning of neurons in mammalian brain. Reelin is a glycoprotein secreted from Cajal‐Reztuis cells in marginal zone of cerebral cortex, and its receptors are Apolipoprotein E receptor 2 (ApoER2) or very low density lipoprotein receptor (VLDLR) expressed on migrating neurons. When Reelin binds to ApoER2 or VLDLR, an adaptor protein Dab1 bound to the receptors undergoes Tyr phosphorylation that is essential for Reelin signaling. We reported previously that Cdk5‐p35 phosphorylates Dab1 at Ser400 and Ser491 and the phosphorylation regulates its binding to CIN85, which is an SH3‐containing multiadaptor protein involved in endocytic downregulation of receptor‐tyrosine kinases. However, the interaction of CIN85 with Dab1 has not been addressed in neurons. We examined here a possibility that CIN85 has a role in Reelin signaling. We found nonpho‐sphorylated Dab1‐mediated colocalization of CIN85 with ApoER2. The colocalization of CIN85 with ApoER2 was increased in neurons stimulated with Reelin repeats 3‐6, an active Reelin fragment. The stimulation recruited CIN85 to domains in plasma membrane where it colocalized with ApoER2 and Dab1 and then to EEA1‐labeled early endosomes in the cytoplasm. In addition, Tyr phosphorylation of Dab1 strengthened the binding to CIN85. These results suggest that CIN85 participates in Reelin signaling through the binding to Dab1.     

The optimal trough-guided monitoring of vancomycin in children: Systematic review and meta-analyses

We carried out a systematic review and meta-analysis exploring the relationship between vancomycin (VCM) trough concentrations and its effectiveness and nephrotoxicity in pediatric patients. We conducted our analysis using MEDLINE, Web of Sciences, and Cochrane Register of Controlled Trials as electronic databases (June 29, 2019). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. We identified 16 studies that were eligible for the meta-analysis. A total of 351 and 3,266 patients were included in the analysis for effectiveness and nephrotoxicity, respectively. Pediatric MRSA infection patients with VCM trough concentrations ≥ 10 μg/mL had significantly lower treatment failure rates (OR 0.54, 95% CI 0.30–0.96). The incidence of nephrotoxicity was significantly higher in trough concentrations ≥ 15 μg/mL than when they were < 15 μg/mL (OR 3.02, 95% CI 2.08–4.38). We identified the optimal VCM trough concentrations associated with effectiveness and nephrotoxicity in pediatric patients with MRSA infection. Further prospective studies are needed to find optimal dosing and monitoring strategy on VCM in pediatric population.     

Regulation of nuclear retention of glucocorticoid receptor by nuclear Hsp90

Heat shock protein 90 (Hsp90) has been demonstrated in both cytoplasm and nucleus, and regulates cytoplasmic retention of glucocorticoid receptor (GR). However, the role of nuclear Hsp90 in GR trafficking is less characterized. The present study examined the role of Hsp90 in nuclear retention of GR after ligand withdrawal. Hsp90 inhibitors; geldanamycin (GA) and radicicol (Rad), significantly accelerated nuclear export of GR after withdrawal of ligands including dexamethasone, corticosterone and RU486. GA accelerated relocalization of GR in the cytoplasm even when reimport of GR into the nucleus was inhibited by okadaic acid or when novel GR synthesis was inhibited by cycloheximide. Overexpression of wild type or nuclear-targeted Hsp90 attenuated Hsp90 inhibitor-induced acceleration of GR nuclear export, although nuclear Hsp90 showed higher activity than the wild type. Only nuclear-targeted Hsp90 prolonged basal nuclear retention of GR after withdrawal of dexamethasone and corticosterone. These results suggest that nuclear Hsp90 regulates the nuclear retention of GR.