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A novel primase inhibitor, Sch 642305 (1), was isolated from the fermentation broth of the fungal culture Penicillium verrucosum. The structure of 1 was elucidated on the basis of MS and NMR spectroscopic data as a new and unusual bicyclic 10-membered macrolide. The absolute configuration of the asymmetric centers was determined by X-ray crystallographic analysis of the p-bromobenzoate derivative (3). Compound 1 exhibited inhibitory activity against bacterial DNA primase enzyme with an EC(50) of 70 microM.

Can biomarkers improve prediction of future cardiovascular events in patients with cardiovascular disease?

OBJECTIVE The goal of this study was to evaluate the effects of conservative treatment and fibroblast growth factor (FGF) applied directly or via Gelfoam on the healing of large traumatic tympanic membrane perforations (TMPs) in humans. STUDY DESIGN Prospective, randomized, controlled trial. METHODS A randomized prospective analysis was performed between February 2009 and January 2011 for the treatment of traumatic TMPs in humans that affected greater than 50% of the TM. The closure rate, closure time, hearing gain, and rate of otorrhea were compared among the direct application of FGF, FGF via Gelfoam, and conservative treatment. RESULTS A total of 94 patients were analyzed. The closure rates of large perforations in the direct FGF application, FGF via Gelfoam, and observation groups were 100%, 97%, and 55%, respectively. FGF-treated groups had significantly improved closure rates compared with the observation group (p 0.05). FGF-treated groups showed shorter mean closure times compared with the observation group (p 0.05).All perforations were closed within 2 weeks, regardless of the presence of curled edges in the FGF-treated groups.

Female 35 (70.0%) 45 (76.3%) 0.460 Age (years) 71.4611.7 65.7615.4 0.036* Diabetes mellitus 23 (46.0%) 18 (30.5%) 0.096 Hypertension 35 (70.0%) 34 (57.6%) 0.182 History of CAD 7 (14.0%) 7 (11.9%) 0.740 Preceding stressors 33 (66.0%) 52 (88.1%) 0.005* Stressors, physical:emotional 33:0 (100%:0%) 49:3 (94.2%:5.8%) 0.008* ST-segment elevation 17 (34.7%) 19 (32.8%) 0.833 T-wave inversion 37 (75.5%) 44 (75.9%) 0.966 Congestive heart failure 25 (50.0%) 24 (40.7%) 0.330 Chest pain 22 (44.0%) 20 (33.9%) 0.280 Shock 11 (22.0%) 19 (28.8%) 0.417 LV EF, initial (%) 43.169.8 41.0610.4 0.297 LV EF, follow-up (%) 48.669.4 54.468.0 0.003* Hemoglobin (g/dL) 10.9762.07 12.2562.05 0.002* Hs-CRP (mg/dL) 61.6667.5 68.9679.2 0.626 Troponin I (ng/mL), peak 5.72610.03 5.10610.86 0.771 NT-pro-BNP (pg/mL), peak 15,287612,342 11,386611,411 0.368

The novel bromotyrosine derivative verongamine [1] has been isolated from the marine sponge Verongula gigantea. The isolation of verongamine was facilitated by employing histamine-H3 bioassay-guided fractionation. Verongamine is a specific histamine-H3 antagonist at concentrations as low as 1 microgram/ml.

Source Citation Ebrahim S, Taylor F, Ward K, et al. Multiple risk factor interventions for primary prevention of coronary heart disease. Cochrane Database Syst Rev. 2011;(1):CD001561. 21249647

Background The Screening for Heart Attack Prevention and Education (SHAPE) Task Force recommends noninvasive atherosclerosis imaging of all asymptomatic men (aged 45-75 years) and women (aged 55-75 years), except those at very low risk, to augment conventional cardiovascular risk assessment algorithms. Methods Among 2611 participants in the Dallas Heart Study aged 30 to 65 years who underwent computed tomography to measure coronary artery calcification, low-density lipoprotein cholesterol (LDL-C) therapeutic targets were calculated using both National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) and SHAPE algorithms. The proportion of subjects reclassified as being “at goal” for LDL-C vs “not at goal” after implementation of the SHAPE recommendations was determined. Results More subjects were identified with LDL-C levels greater than or equal to goal based on SHAPE than on NCEP-ATP III (27.4% vs 21.6%), with 7.0% of individuals reclassified as having unmet LDL-C goals and 1.1% of individuals reclassified as at goal. When more aggressive optional LDL-C goals were implemented, 31.7% had LDL-C levels greater than or equal to goal using SHAPE recommendations vs 28.1% using NCEP-ATP III recommendations, with 6.3% of subjects reclassified as being not at goal and 2.7% as being at goal. Conclusions The SHAPE recommendations resulted in bidirectional reclassification of eligibility for lipid-lowering therapy in subjects aged 30 to 65 years. While broad implementation of these recommendations would modestly increase cholesterol-lowering drug use in this age range, the magnitude of the increase depends on whether standard or optional LDL-C goals are targeted.

High performance preparative chromatographic systems are described which facilitate the isolation and purification of some naturally occurring, novel mycinamicins. Facile separation and excellent recovery of these macrolide antibiotics was obtained with a C-18 radially compressed Prep 500 cartridge using methanol/trifluoroacetic acid mobile phases. Semi-preparative chromatography on a C-8 reversed-phase sorbent incorporating a volatile ammonium acetate buffer was utilized in the final purification of an enriched mixture of intermediate components. Monitoring of isolated fractions with analytical HPLC provided direct support for the effectiveness of the preparative isolation.