Rubral tremor associated with cavernous angioma of the midbrain

The insecticidal activity of five alkylfurans against the generalist insect herbivore beet armyworm, Spodoptera exigua, was examined. Two naturally occurring compounds, the avocadofurans 2-(pentadecyl)furan (1) and 2-(heptadecyl)furan (2), previously isolated from specialized avocado idioblast oil cells, and three homologues, 2-(tetradecyl)furan (3), 2-(hexadecyl)furan (4), and 2-(octadecyl)furan (5), were synthesized. Bioassays of alkylfurans 1-5 using a 9-day diet-incorporation initiated with neonates showed that all alkylfurans tested significantly increased S. exigua larval mortality and reduced larval weights, with maximal biological activity detected among the naturally occurring alkylfurans 1 and 2.     

Actions of serotonergic agents on hypothalamic-pituitary-adrenal axis activity in the rat

1. The effects of ipsapirone, nefazodone, tiaspirone, BMS-20661, buspirone and gepirone on the hypothalamic-pituitary-adrenal (HPA) axis were studied. These drugs were selected because they have serontonin 1A (5-HT1A) receptor-binding capability and have the potential for therapeutic activity in the treatment of major affective or anxiety disorders or both. 2. Plasma corticosterone level was used as the end point for determining the effect of each drug on the HPA axis. Each drug increased the plasma corticosterone levels in a dose-dependent manner. The ED50 values were 0.8 mg/kg for BMS-20661, 3.5 mg/kg for gepirone, 3.9 mg/kg for buspirone, 5.3 mg/ kg for tiaspirone, 10.5 mg/kg for ipsapirone and 73.5 mg/kg for nefazodone. Ipsapirone and buspirone were more efficacious than the other four drugs. 3. The effect of a 10-mg/kg (35 mg/kg for nefazodone) test dose of each drug reached a peak between 30 min and 1 hr, and plasma corticosterone levels generally returned to control levels after 2 hr. 4. When the drugs were given 30 min before decapitation, in conjunction with a rotatory stress, BMS-20661 significantly inhibited the stress-induced rise, whereas ipsapirone and gepirone caused a significant increase in plasma corticosterone levels. However, when the drugs were given 2 hr before decapitation, nefazodone caused a significant decrease, whereas ipsapirone, BMS-20661 and gepirone produced significant increases in HPA axis activity. An 0800 hr dose of 0.1 mg/kg of dexamethasone suppressed the 1500 hr HPA activity by 73.1%. The 0.1-mg/kg dose of dexamethasone significantly reduced the drug-activated HPA axis activity of all of the drugs from their saline-control levels. The rank order, from least to greatest inhibitory effect, produced by this dexamethasone treatment on the drug-control levels was gepirone (-42.6%), tiaspirone (-48.9%), buspirone (-56.1%), nefazodone (-68.5%), insapirone (-70.0%), and BMS-20661 (-74.3%).     

Evaluation of the echinocandin antifungal MK-0991 (L-743,872): efficacies in mouse models of disseminated aspergillosis, candidiasis, and cryptococcosis

The in vivo activity of the Merck antifungal echinocandin drug candidate MK-0991 (L-743,872) was evaluated in mouse models of disseminated candidiasis, aspergillosis, and cryptococcosis. The echinocandins are potent inhibitors of 1,3-beta-D-glucan synthase. Two models of disseminated candidiasis were used. In a Candida albicans mouse survival model with both DBA/2N and CD-1 mice, estimates of the 50% effective doses (ED50s) of MK-0991 were 0.04 and 0.10 mg/kg of body weight/dose at 21 days after challenge, respectively. In a C. albicans target organ assay (TOA) with DBA/2N mice, MK-0991 at levels of > or =0.09 mg/kg/dose significantly reduced the numbers of C. albicans CFU/g of kidneys compared to the numbers in the kidneys of control mice from 1 to 28 days after challenge. Even when given as a single intraperitoneal dose either 30 min or 24 h after challenge, MK-0991 was effective and significantly reduced the numbers of C. albicans CFU/g of kidney compared to those in the controls. MK-0991 was >300-fold less active when it was administered orally than when it was administered parenterally. MK-0991 was efficacious in mouse TOAs against other C. albicans strains and Candida species including Candida tropicalis, Candida (Torulopsis) glabrata, Candida lusitaniae, Candida parapsilosis, and Candida krusei. MK-0991 was ineffective against disseminated Cryptococcus neoformans infections. In the model of disseminated aspergillosis in mice, MK-0991 at doses of > or =0.02 mg/kg/dose significantly prolonged the survival of DBA/2N mice, with estimates of the ED50 and ED90 of MK-0991 being 0.03 and 0.12 mg/kg/dose, respectively, at 28 days after challenge. MK-0991 is a potent, parenterally administered therapeutic agent against disseminated candidiasis and aspergillosis that warrants further investigation in human clinical trials.     

Early ambulation after coronary angioplasty and stenting with six French guiding catheters and low-dose heparin

The safety and feasibility of early ambulation was evaluated prospectively in 907 patients undergoing elective coronary angioplasty and stenting with the use of 6Fr guiding catheters, low-dose heparin (5,000 IU), and immediate postprocedural sheath removal by comparing ambulation after 4 hours with immobilization for at least 12 hours. Because no excess in puncture site complications (2.3% vs 2.2%) could be demonstrated after 4-hour ambulation, it is concluded that early ambulation after 6Fr guiding catheter angioplasty by the femoral route with low-dose heparin is feasible, safe, and may facilitate a shorter hospital stay.     

Stability of sulfonamide antibiotics in spiked pig liver tissue during frozen storage

A bulk portion of homogenized pig liver tissue was spiked at room temperature with 0.2 mg/kg (twice the Australian maximum residue limit) of each of sulfathiazole, sulfachlorpyridazine, sulfadimidine (sulfamethazine), sulfaquinoxaline, and sulfadimethoxine. After subsampling and packaging, selected individual packaged units were tested to confirm homogeneity of the prepared material. The material was stored frozen at -20 degrees C and analyzed in replicate by liquid chromatography on 11 sampling dates over a period of about 6 months. Analytical data were plotted on a log-linear scale and subjected to linear regression on the basis of first-order kinetics for the decay. Storage stabilities (decay half-lives at -20 degrees C) calculated from the mean slope of regression lines were sulfadimethoxine, 567 days; sulfadimidine, 457 days; sulfachlorpyridazine, 312 days; sulfathiazole, 291 days; and sulfaquinoxaline, 271 days. Significant depletion (65% loss) of residue was observed for sulfaquinoxaline during preparation of spiked bulk liver tissue. An extension of the study to measure the storage stability of sulfaquinoxaline under accelerated decay conditions (refrigerator temperature, 4 degrees C) showed it to be relatively unstable, with a decay half-life of 11 days. Results demonstrate the need for both regulatory agencies and testing laboratories to be aware of potential errors associated with improper transport, storage, and handling of tissue samples submitted for antibiotic testing.