ABSTRACT
INTRODUCTION: Mineral trioxide aggregate (MTA) materials have been used for many years as a pulp therapy material. The most widely used product, ProRoot MTA (Dentsply, Tulsa, OK), has a major drawback in that it causes tooth discoloration. Alternatives have recently been developed such as ENDOCEM Zr (MARUCHI, Wonju, Korea) and RetroMTA (BioMTA, Seoul, Korea). The purpose of this study was to compare the discoloration of these various MTA-based materials. METHODS: Discoloration of discs prepared from 4 different MTA-based materials (ProRoot MTA, MTA Angelus [Angelus, Londrina, PR, Brazil], ENDOCEM Zr, and RetroMTA) were observed at 15 and 30 minutes after exposure to light at an intensity of 1000 mA/cm(2). In a tooth model, 12 premolars were used per each group to retrofill the pulp chamber with MTA-based materials. The degree of discoloration was measured over a 16-week period using a digital spectrophotometer. RESULTS: Distinct color changes were observed for discs made from ProRoot MTA and MTA Angelus, but no clear change was observed for those made from either ENDOCEM Zr or RetroMTA. In the tooth model, more distinct, time-dependent color changes were observed for teeth filled with ProRoot MTA and MTA Angelus than for those filled with ENDOCEM Zr and RetroMTA. CONCLUSIONS: Less discoloration was observed with ENDOCEM Zr and RetroMTA (which contain zirconium oxide) than with ProRoot MTA and MTA Angelus (which contain bismuth oxide) in both of the test models used.
Subject(s)
Aluminum Compounds/adverse effects , Calcium Compounds/adverse effects , Oxides/adverse effects , Root Canal Filling Materials/adverse effects , Silicates/adverse effects , Tooth Discoloration/chemically induced , Adolescent , Adult , Bismuth/adverse effects , Child , Drug Combinations , Female , Humans , Male , Materials Testing , Time Factors , Young Adult , Zirconium/adverse effectsABSTRACT
Synthesis of phosphonooxymethyl derivatives of ravuconazole, 2 (BMS-379224) and 3 (BMS-315801) and their biological evaluation as potential water-soluble prodrugs of ravuconazole are described. The phosphonooxymethyl ether analogue 2 (BMS-379224) and N-phosphonooxymethyl triazolium salt 3 (BMS-315801) were both prepared from ravuconazole (1) and bis-tert-butyl chloromethylphosphate, but under two different conditions. Both derivatives were highly soluble in water and converted to the parent in alkaline phosphatase, and also in vivo (rat). However, BMS-315801 was found to be less stable than BMS-379224 in water at neutral pH. BMS-379224 (2) has proved to be one of the most promising prodrugs of ravuconazole that we tested, and it is currently in clinical evaluation as an intravenous formulation of the broad spectrum antifungal azole, ravuconazole.
Subject(s)
Antifungal Agents/chemical synthesis , Antifungal Agents/pharmacology , Prodrugs/chemical synthesis , Prodrugs/pharmacology , Thiazoles/chemical synthesis , Thiazoles/pharmacology , Triazoles/chemical synthesis , Triazoles/pharmacology , Animals , Antifungal Agents/pharmacokinetics , Candidiasis/drug therapy , Candidiasis/microbiology , Drug Stability , Female , Humans , Indicators and Reagents , Infusions, Intravenous , Mice , Mice, Inbred ICR , Prodrugs/pharmacokinetics , Rats , Solubility , Structure-Activity Relationship , Survival , Thiazoles/pharmacokinetics , Triazoles/pharmacokineticsABSTRACT
Systemically injected 2'-O-methoxyethyl (2'-O-MOE)-phosphorothioate and PNA-4K oligomers (peptide nucleic acid with four lysines linked at the C terminus) exhibited sequence-specific antisense activity in a number of mouse organs. Morpholino oligomers were less effective, whereas PNA oligomers with only one lysine (PNA-1K) were completely inactive. The latter result indicates that the four-lysine tail is essential for the antisense activity of PNA oligomers in vivo. These results were obtained in a transgenic mouse model designed as a positive readout test for activity, delivery, and distribution of antisense oligomers. In this model, the expressed gene (EGFP-654) encoding enhanced green fluorescence protein (EGFP) is interrupted by an aberrantly spliced mutated intron of the human beta-globin gene. Aberrant splicing of this intron prevented expression of EGFP-654 in all tissues, whereas in tissues and organs that took up a splice site-targeted antisense oligomer, correct splicing was restored and EGFP-654 expression upregulated. The sequence-specific ability of PNA-4K and the 2'-O-MOE oligomers to upregulate EGFP-654 provides strong evidence that systemically delivered, chemically modified oligonucleotides affect gene expression by sequence-specific true antisense activity, validating their application as potential therapeutics.
