T-8581, a new orally and parenterally active triazole antifungal agent: in vitro and in vivo evaluations.

T-8581 is a new water-soluble triazole antifungal agent. The geometric mean IC80s (GM-IC80S; where the IC80 is the lowest drug concentration which reduced the optical density at 630 nm by 80% compared with the optical density at 630 nm of the drug-free control) for Candida albicans were as follows: T-8581, 0.218 microgram/ml; fluconazole; 0.148 microgram/ml; and itraconazole, 0.0170 microgram/ml. For Cryptococcus neoformans the GM-IC80s were as follows: T-8581, 9.28 micrograms/ml; fluconazole, 4.00 micrograms/ml; and itraconazole, 0.119 microgram/ml. For Aspergillus fumigatus the GM-IC80s were as follows: T-8581, 71.0 micrograms/ml; fluconazole, 239 micrograms/ml; and itraconazole, 0.379 microgram/ml. Against systemic candidiasis in mice, the 50% effective doses (ED50s) of T-8581, fluconazole, and itraconazole (given orally) were 0.412, 0.392, and > 320 mg/kg of body weight, respectively. Against systemic aspergillosis in mice, the ED50s of T-8581, fluconazole, and itraconazole (given orally) were 50.5, 138, > 320 mg/kg, respectively. T-8581 was also efficacious when it was given parenterally (ED50, 59.2 mg/kg), while the ED50 of fluconazole given parenterally was > 20 mg/kg. Against systemic aspergillosis in rabbits, T-8581 was more effective than fluconazole and itraconazole in prolonging the life span. The high concentrations of T-8581 were observed in the sera of mice, rats, rabbits and dogs. Species differences in half-lives and areas under the concentration-time curves were observed, with the values for mice, rats, rabbits, and dogs increasing in that order. These results suggest that T-8581 would be a potentially effective antifungal drug for oral and parenteral use.

A columnar arrangement of dendritic processes of entorhinal cortex neurons revealed by a monoclonal antibody.

Immunohistochemical screening of the cat limbic system using a panel of monoclonal antibodies (MAbs) revealed that MAb R2D5 specifically labeled a subset of layer 3 cells in the entorhinal cortex, while leaving layer 2 cells unlabeled. The apical dendrites of the R2D5-positive layer 3 cells tended to gather and formed columnar structures which penetrated layer 2 and climbed to the surface of entorhinal cortex.

Rapid ventricular parasystole with possible multilevel exit block.

A case of ventricular parasystole firing at the extremely rapid rate of 214 beats per minute in a 73 year old woman is described. Manifest cycle lengths of parasystolic complexes varied widely due to variable degrees of exit block, which could be best interpreted by the concept of multilevel block or alternating Wenckebach periodicity in the ventriculo-ectopic junction. Discontinuation of digoxin reduced the degree of exit block and unmasked parasystolic tachycardia.