[Molecular mechanism of action of ezetimibe and recent therapeutics]

High blood Low density lipoprotein cholesterol is a major cardiovascular risk factor and must be the primary target of primary and secondary heart protection. Statines, 3-hydroxy-3-methylglutaryl-coenzyme A [HMG-CoA] reductase inhibitors, are the cornerstone of lipid-lowering therapy for reducing LDLc levels. However, some patients at high risk fail to achieve LDLc target despite high-dose statin therapy. Statins may also induce adverse effects. Ezetimibe is the first potent cholesterol absorption inhibitor. Several ongoing clinical interventional trials will shed more light on the association statin plus ezetimibe in high risk patients. A better understanding of intestinal cholesterol absorption will lead to novel approaches for the prevention and treatment of hyperlipidemia

Antimycotic susceptibility testing of mould-fungi with allylamines by disk diffusion.

Susceptibility testing of 17 clinical isolates of mould-fungi, which included Aspergillus spp., (8) Penicillium spp., (2) Paecilomyces spp., (1) Cladosporium spp., (1) Pyrenochaeta romeroi (1) Rhizopus spp., 2. Syncephalastrum spp., (1) and Mortierella spp., (1) were carried out against allylamines-naftifine and terbinafine-(Sandoz Forchungsinstitut) by agar dilution and disk diffusion techniques. Terbinafine was more active than naftifine inhibiting 50 and 90% of the fungi other than zygomycetes at a concentration of 0.5 and 1 microgram/ml whereas the values for naftifine were 2.5 and 10 micrograms/ml. The MIC range for zygomycetes for terbinafine and naftifine were 1-->100 and 100-->100 respectively. The MICs and the sizes of zones of inhibition around the disks correlated well and the degree of correlation was measured by regression analysis. The correlation coefficients for naftifine and terbinafine were-0.9597 and -0.9174 (P < 0.007) respectively.

Antidermatophytic activity of allylamine derivatives.

The allylamine derivatives are a new class of synthetic antifungal agents. The antidermatophytic activity of the two main compounds, naftifine and terbinafine were compared in vitro with those of ketoconazole and itraconazole by agar dilution. Eighty eight clinical isolates of dematophytes comprising of Microsporum canis (50), M. audouinii (5), Trichophyton rubrum (6) T. mentagrophytes (5), T. violaceum (12), T. simii (5), T. verrucosum (1), T. soudanense (1), T. erinacie (1) and Epidermophyton floccosum (2) were tested. Terbinafine was found to be most active, inhibiting 68 of the 88 isolates at a concentration of 0.01 ug ml-1 and all at 0.1 ug ml. (Minimum inhibitory concentration - MIC range < or = 0.0001-0.1 ug ml-1). Naftifine inhibited 84 isolates at a concentration of 0.1 ug ml-1 and all at 0.5 ug ml-1 (MIC range 0.001-0.5 ug ml-1). Itraconazole required 0.1 ug ml-1 for inhibiting 50 isolates and 0.5 ug ml-1 for 85 isolates (MIC range 0.01-1 ug ml-1) whereas ketoconazole inhibited 71 isolates at 1 ug ml-1 and 87 at 2.5 ug ml-1 (MIC range 0.01-5 ug ml-1).

Antifungal activity of allylamine derivatives.

The antifungal activity of the two allylamine derivatives, naftifine and terbinafine was investigated against 25 clinical isolates of filamentous fungi by agar dilution method. The isolates included Aspergillus sp. (10), Penicillium sp. (3), Cladosporium sp. (3), Rhizopus sp. (3), Paecilomyces sp. (2), Syncephalastrum sp. (1), Pyrenochaeta romeroi (1), Piedraia hortae (1) and Mortierella sp. (1). Terbinafine was found to be more active than naftifine, inhibiting 50 per cent (MIC 50) and 90 per cent (MIC 90) of the isolates of Aspergillus sp., at 0.1 and 0.5 microgram/ml respectively. The MIC 50s for the other isolates of hyalohyphomycetes, dematiaceous fungi and zygomycetes were 1, 5 and 100 micrograms/ml respectively. Naftifine inhibited 50 and 90 per cent of the Aspergillus sp., at 1 and 5 micrograms/ml, respectively. The MIC 50s for the other hyalohyphomycetes, dematiaceous fungi and zygomycetes were 5, 10 and 100 micrograms/ml respectively.