Stoichiometry of hemolysis by the polyene antibiotic lucensomycin.

The stoichiometry of hemolysis by the polyene antibiotic lucensomycin was investigated. It appears that hemolysis occurs only when a relatively high fraction (probably between 15 and 40%) of the cholesterol sites in the erythrocyte membrane have combined with the polyene. Also in phospholipid-cholesterol vesicles the increase of permeability requires occupancy of 40-50% of the existing cholesterol sites. As for the possible cooperative effect in the hemolytic process, it is probable that several (at least 9-10) lucensomycin-cholesterol adducts must interact on each side of the membrane to form an aqueous channel; the distribution of these adducts in the erythrocyte membrane occurs, however, apparently at random

A class-A beta-lactamase from Pseudomonas stutzeri that is highly active against monobactams and cefotaxime.

A beta-lactamase produced by Pseudomonas stutzeri was purified to protein homogeneity, and its physicochemical and catalytic properties were determined. Its profile was unusual since, in addition to penicillins, the enzyme hydrolysed second- and third-generation 'beta-lactamase-stable' cephalosporins and monobactams with similar efficiencies. On the basis of the characteristics of the interaction with beta-iodopenicillanic acid, the enzyme could be classified as a class-A beta-lactamase. However, when compared with most class-A beta-lactamases, it exhibited significantly lower kcat./Km values for the compounds usually considered to be the best substrates of these enzymes

ENCAPSULATION AND EFFLUX OF LACTONE AND HYDROXY ACID FORMS OF SIMVASTATIN IN REVERSE-PHASE EVAPORATION VESICLES

Simvastatin( SV) is the lactone prodrug of SVA, a hydroxymethylglutaryl-CoAre ductasei nhibitor, which in its activef orm of a hydroxya cid (SVA) lowersp lasmac holesterolt hrough inhibiting its endogenouss ynthesisT. he presentp aper describesa n attempt to encapsulateb oth drugsi n reverse-phasee vaporation( REV) vesicles.T he experimentalr esultsc an be summarizeda s follows: (i) both drugs( SV and SVA) are encapsulatede fficiently into DPPC liposomesw ith high yield; (ii) in all preparationst ested,t he more hydrophilic SVA is encapsulatedto a considerablyg reater extent than SV, reaching approx.6 0Voi n the caseo f DPPC liposomes; (iii) the presence of cholesterol in the vesicle wall markeldy reduces this capacity; (iv) it is possible to control the release of drug from the liposomesb y modifuingt he lipid compositiono f the vesiclesT. he procedureo f encapsulatioinn to liposomesin principle should permit the direct administrationo f SVA, thereby reducingt he toxicity associatedw ith high doseso f SV