Percutaneous Intervention of LVAD Outflow Graft Obstruction and Thrombosis.

Left ventricular assist devices serve as a salvage therapy for patients with advanced heart failure. Complications such as thrombosis and obstruction can lead to acute device malfunction, posing significant clinical risks. A multidisciplinary approach is crucial for management. Few cases in the literature have demonstrated the safety and efficacy of percutaneous intervention, which holds significant value due to its less invasive nature and minimal risk of morbidity, especially in high-risk surgical patients.

A Novel Role for RARα Agonists as Apolipoprotein CIII Inhibitors Identified from High Throughput Screening.

Elevated triglyceride (TG) levels are well-correlated with the risk for cardiovascular disease (CVD). Apolipoprotein CIII (ApoC-III) is a key regulator of plasma TG levels through regulation of lipolysis and lipid synthesis. To identify novel regulators of TG levels, we carried out a high throughput screen (HTS) using an ApoC-III homogenous time resolved fluorescence (HTRF) assay. We identified several retinoic acid receptor (RAR) agonists that reduced secreted ApoC-III levels in human hepatic cell lines. The RARα specific agonist AM580 inhibited secreted ApoC-III by >80% in Hep3B cells with an EC50 ~2.9 nM. In high-fat diet induced fatty-liver mice, AM580 reduced ApoC-III levels in liver as well as in plasma (~60%). In addition, AM580 treatment effectively reduced body weight, hepatic and plasma TG, and total cholesterol (TC) levels. Mechanistically, AM580 suppresses ApoC-III synthesis by downregulation of HNF4α and upregulation of SHP1 expression. Collectively, these studies suggest that an RARα specific agonist may afford a new strategy for lipid-lowering and CVD risk reduction.

Coronary artery vasospasm and cardiogenic shock as the initial presentation for eosinophilic granulomatosis with polyangiitis.

A 68-year-old woman presented to our hospital with unstable angina and was admitted for further evaluation. While hospitalized, she developed persistent angina with hypotension along with ST-segment elevation in leads V1-V2 along with lead aVR elevation on 12-lead electrocardiogram. Coronary angiography revealed diffuse multi-vessel coronary vasospasm most notably in the left anterior descending artery (LAD). Due to incomplete resolution of vasospasm with intracoronary verapamil and nitroglycerin, along with hemodynamic compromise requiring an intra-aortic balloon pump, percutaneous coronary intervention (PCI) of the LAD was performed. Clinical workup revealed hypereosinophlia and elevated IgE; diagnosis of eosinophilic granulomatosis with polyangiitis was confirmed with evidence of radiographic migratory pulmonary infiltrates and airway obstruction on spirometry. The patient had recurrent angina after PCI but her symptoms resolved fully after a course of corticosteroids. We attribute her refractory vasospastic angina to previously undiagnosed small/medium-vessel vasculitis. .

Formal synthesis of (+/-)-roseophilin.

A formal synthesis of (+/-)-roseophilin is described. Scandium(III)-catalyzed Nazarov cyclization of 2,5-disubstituted N-tosylpyrrole 19 gives a 5,5'-fused ketopyrrole, and ansa-bridge formation via pi-allyl palladium macrocyclization gives 21.

Polyamines and the NMDA receptor: modifying intrinsic activities with aromatic substituents.

Thirty-four spermidine (SPD) and spermine (SPM) derivatives with aromatic substituents were synthesized and tested as inhibitors of specific binding of the NMDA channel blocker [3H]MK-801 to membranes prepared from rat hippocampus and cerebral cortex. SPD and SPM derivatives with aromatic substituents at the primary amino groups were the most potent inhibitors (IC50 3.9-4.7 microM). These compounds most likely act directly at the NMDA ion channel, since 30 microM SPM had no pronounced influence on their inhibiting activities. SPD derivatives with aromatic substituents at the secondary amino group were either inactive or highly SPM-sensitive inhibitors (IC50 10-82 microM), depending on the size of the substituent. Our results support the hypothesis that an aromatic interaction site near the center of polyamine derivatives contributes to polyamine inverse agonism.