This study investigated the effect of one semester of ESOL education on preservice teachers by examining their perceived knowledge and skill in working with English Language Learner (ELL) students, and their attitude toward having ELL students in their mainstream classrooms. The survey identified two factors: a) Perception of ESOL Knowledge and Skills (PEKS) and b) Attitude Toward Inclusion (ATI). Results showed that preservice teachers’ perceptions of both knowledge & skill (PEKS) changed from introductory to the final ESOL course, and that PEKS changed significantly from pre- to post-test within the same course. No significant changes were found in students’ attitude toward inclusion (ATI) either from course 1 to course 2 or from pre- to post-test within the same course.
Aldehyde oxidase (AOX) is a cytosolic drug-metabolizing enzyme which has attracted increasing attention in drug development due to its high hepatic expression, broad substrate profile and species differences. In contrast, there is limited information on the presence and activity of AOX in extrahepatic tissues including ocular tissues. Because several ocular drugs are potential substrates for AOX, we performed a comprehensive analysis of the AOX1 expression and activity profile in seven ocular tissues from humans, rabbits, and pigs. AOX activities were determined using optimized assays for the established human AOX1 probe substrates 4-dimethylamino-cinnamaldehyde (DMAC) and phthalazine. Inhibition studies were undertaken in conjunctival and retinal homogenates using well-established human AOX1 inhibitors menadione and chlorpromazine. AOX1 protein contents were quantitated with targeted proteomics and confirmed by immunoblotting. Overall, DMAC oxidation rates varied over 10-fold between species (human ˃˃ rabbit ˃ pig) and showed 2- to 6-fold differences between tissues from the same species. Menadione seemed a more potent inhibitor of DMAC oxidation across species than chlorpromazine. Human AOX1 protein levels were highest in the conjunctiva, followed by most posterior tissues, whereas anterior tissues showed low levels. The rabbit AOX1 expression was high in the conjunctiva, retinal pigment epithelial (RPE), and choroid while lower in the anterior tissues. Quantification of pig AOX1 was not successful but immunoblotting confirmed the presence of AOX1 in all species. DMAC oxidation rates and AOX1 contents correlated quite well in humans and rabbits. This study provides, for the first time, insights into the ocular expression and activity of AOX1 among multiple species.
Zomepirac is a nonsteroidal anti-inflammatory drug recently withdrawn from use because of an unexplained high incidence of immunological reactions. It is metabolized in humans to a reactive, unstable acyl glucuronide which accumulates in plasma. Because of the similarity of zomepirac glucuronide to bilirubin glucuronide in structure and stability and the documented irreversible binding of bilirubin to albumin through its acyl glucuronide, we studied the reaction of zomepirac acyl glucuronide with albumin in vitro from pH 5 to 9 and in vivo in six healthy human volunteers who had received a single 100-mg oral dose of zomepirac. Irreversible binding of zomepirac to protein was determined by exhaustive washing of protein, followed by hydrolysis of bound zomepirac-protein adduct with base, extraction of the liberated drug, and chromatographic measurement. Irreversible binding was observed both in vitro and in vivo. The extent of binding in vitro was time- and pH-dependent. In vitro drug binding was also observed for the isomers of zomepirac glucuronide which were formed by intramolecular acyl migration. Irreversible binding in vivo correlated with overall exposure to zomepirac glucuronide when exposure was expressed as the area under the plasma concentration vs. time curve. When probenecid (500 mg, twice daily), which decreases the plasma clearance of zomepirac glucuronide, was administered concurrently with zomepirac, irreversible binding of zomepirac was increased. The nature of the zomepirac protein binding is probably covalent. Formation of irreversibly protein-bound zomepirac occurs via the acyl glucuronide as previously shown for bilirubin glucuronide, and the reaction may be general for other drugs that are metabolized to acyl glucuronides.
1. Suprofen acyl glucuronide, a major metabolite of suprofen in man, is labile, undergoing acyl migration to isomeric conjugates which are not cleaved by β-glucuronidase.2. The pH-dependent degradation of diastereomeric suprofen glucuronides in aqueous buffer increases rapidly near physiological pH with an apparent first-order half life of 1.4 h at pH 7.4.3. Suprofen glucuronide and its isomeric conjugates are reactive with albumin in a pH-dependent manner which corresponds to the stability of the acyl glucuronide. Several per cent of the conjugates added to albumin in solution become covalently bound.4. The covalent binding of suprofen equivalents to albumin is greatly enhanced by the addition of either cyanide or cyanoborohydride anion, which supports the presence of an imine in the process of binding. Release of isomeric conjugates by treatment of the albumin adduct with dilute acid also supports covalent binding via an imine.5. The covalent binding of suprofen to proteins through its reactive acyl glucuronide may be of toxicological importance and relevant to the acute renal toxicity observed for suprofen in man.
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