Large coronary aneurysm following laser angioplasty of the left anterior descending coronary artery.

Coronary aneurysm is a rare complication after coronary excimer laser angioplasty. A 45-year-old woman underwent laser angioplasty and bare metal direct stenting of the proximal segment of the left anterior descending artery (LAD); after 3 months, angiographic follow-up showed significant ostial stenosis of the LAD with a large sacciform aneurysm and diffuse intrastent restenosis.

Discovery of the first small molecule inhibitor of human DDX3 specifically designed to target the RNA binding site: towards the next generation HIV-1 inhibitors.

Efficacy of currently approved anti-HIV drugs is hampered by mutations of the viral enzymes, leading invariably to drug resistance and chemotherapy failure. Recent data suggest that cellular co-factors also represent useful targets for anti-HIV therapy. Here we describe the identification of the first small molecules specifically designed to inhibit the HIV-1 replication by targeting the RNA binding site of the human DEAD-Box RNA helicase DDX3. Optimization of a easily synthetically accessible hit (1) identified by application of a high-throughput docking approach afforded the promising compounds 6 and 8 which proved to inhibit both the helicase and ATPase activity of DDX3 and to reduce the viral load of peripheral blood mononuclear cells (PBMC) infected with HIV-1.

Design, synthesis, biological activity, and ADME properties of pyrazolo[3,4-d]pyrimidines active in hypoxic human leukemia cells: a lead optimization study.

A family of dual Src/Abl inhibitors characterized by a substituted pyrazolo[3,4-d]pyrimidine scaffold was previously reported by us and proved to be active against several tumor cell lines. Among these compounds, a promising antileukemia lead (1) has been recently identified, but, unfortunately, it suffers from substandard pharmaceutical properties. Accordingly, an approach for the optimization of the lead 1 is described in the present work. A series of more soluble pyrazolo[3,4-d]pyrimidine derivatives were rationally designed and proved to maintain the dual Src/Abl activity of the lead. Selected compounds showed an interesting activity profile against three different leukemic cells also in hypoxic conditions, which are usually characterized by imatinib-resistance. Finally, in vitro ADME properties (PAMPA permeation, water solubility, microsomal stability) for the most promising inhibitors were also evaluated, thus allowing the identification of a few optimized analogues of lead 1 as promising antileukemia agents.

Ambulatory pulse pressure, left ventricular hypertrophy and function in arterial hypertension.

BACKGROUND: A wide pulse pressure (PP) can provide important risk assessment information about myocardial infarction, carotid artery atherosclerosis, and global cardiovascular risk. Ambulatory pulse pressure (APP) does not have a well-known prognostic value in hypertensive patients. METHODS: To evaluate the relationship among high APP, atrial volumes, and cardiac function, an observational study was performed on 108 untreated non-elderly hypertensive patients (mean age 54.23 +/- 7.12). Twenty-four-hour ambulatory blood pressure monitoring, Doppler and echocardiographic measurements of systolic, diastolic function, left and right atrial volumes, left ventricular mass index and dimensions, were performed in subjects with both clinic and APP > 60 mmHg (APP1 Group). A control group of hypertensive selected subjects with both clinic and APP < 60 mmHg was chosen (APP 2 Group). RESULTS: The APP1 group showed left atrial volume enlargement, high left ventricular mass index, and impaired diastolic function. A positive correlation was found in the APP1 group results among left ventricular end diastolic diameter (r = 0.39, P < 0.01), left atrial volume (0.38, P < 0.05), and left ventricular mass index (r = 0.33, P < 0.05); clinic PP showed a statistically significant correlation with left atrial volume, left ventricular end diastolic diameter, and left ventricular mass index only in the APP1 group. CONCLUSIONS: These results suggest that elevated APP can be considered an effective predictor of cardiovascular risk in hypertensive subjects. In these patients echocardiographic evaluation of left ventricular function and morphology can increase the prognostic value of PP.