Specific Increase in MDR1 Mediated Drug-Efflux in Human Brain Endothelial Cells following Co-Exposure to HIV-1 and Saquinavir

Persistence of HIV-1 reservoirs within the Central Nervous System (CNS) remains a significant challenge to the efficacy of potent anti-HIV-1 drugs. The primary human Brain Microvascular Endothelial Cells (HBMVEC) constitutes the Blood Brain Barrier (BBB) which interferes with anti-HIV drug delivery into the CNS. The ATP binding cassette (ABC) transporters expressed on HBMVEC can efflux HIV-1 protease inhibitors (HPI), enabling the persistence of HIV-1 in CNS. Constitutive low level expression of several ABC-transporters, such as MDR1 (a.k.a. P-gp) and MRPs are documented in HBMVEC. Although it is recognized that inflammatory cytokines and exposure to xenobiotic drug substrates (e.g HPI) can augment the expression of these transporters, it is not known whether concomitant exposure to virus and anti-retroviral drugs can increase drug-efflux functions in HBMVEC. Our in vitro studies showed that exposure of HBMVEC to HIV-1 significantly up-regulates both MDR1 gene expression and protein levels; however, no significant increases in either MRP-1 or MRP-2 were observed. Furthermore, calcein-AM dye-efflux assays using HBMVEC showed that, compared to virus exposure alone, the MDR1 mediated drug-efflux function was significantly induced following concomitant exposure to both HIV-1 and saquinavir (SQV). This increase in MDR1 mediated drug-efflux was further substantiated via increased intracellular retention of radiolabeled [3H-] SQV. The crucial role of MDR1 in 3H-SQV efflux from HBMVEC was further confirmed by using both a MDR1 specific blocker (PSC-833) and MDR1 specific siRNAs. Therefore, MDR1 specific drug-efflux function increases in HBMVEC following co-exposure to HIV-1 and SQV which can reduce the penetration of HPIs into the infected brain reservoirs of HIV-1. A targeted suppression of MDR1 in the BBB may thus provide a novel strategy to suppress residual viral replication in the CNS, by augmenting the therapeutic efficacy of HAART drugs.

The effect of multimedia instruction on achievement of college history students

The purpose of this study was to investigate the effect of multimedia instruction on achievement of college students in AMR 2010 from exploration and discovery to 1865. A non-equivalent control group design was used. The dependent variable was achievement. The independent variables were learning styles, method of instruction, and visual clarifiers (notes). The study was conducted using two history sections from Palm Beach Community College, in Boca Raton, Florida, between August and December, 1998. Data were obtained by means of placement scores, posttests, the Productivity Environmental Preference Survey (PEPS), and a researcher-developed student survey. Statistical analysis of the data was done using SPSS statistical software. Demographic variables were compared using Chi square. T tests were run on the posttests to determine the equality of variances. The posttest scores of the groups were compared using the analysis of covariance (ANCOVA) at the .05 level of significance. The first hypothesis there is a significant difference in students' learning of U.S. History when students receive multimedia instruction was supported, F (1, 52) = 16.88, p < .0005, and F = (1, 53) = 8.52, p < .005 for Tests 2 and 3, respectively. The second hypothesis there is a significant difference on the effectiveness of multimedia instruction based on students' various learning preferences was not supported. The last hypotheses there is a significant difference on students' learning of U.S. History when students whose first language is other than English and students who need remediation receive visual clarifiers were not supported. Analysis of covariance (ANCOVA) indicated no difference between the groups on Test 1, Test 2, or Test 3: F (1, 45) = .01, p < .940, F (1, 52) = .77, p < .385, and F (1, 53) =.17, p < .678, respectively, for language. Analysis of covariance (ANCOVA) indicated no significant difference on Test 1, Test 2, or Test 3, between the groups on the variable remediation: F (1, 45) = .31, p < .580, F (1, 52) = 1.44, p < .236, and F (1, 53) = .21, p < .645, respectively. ^

The effect of multimedia instruction on achievement of college history students

The purpose of this study was to investigate the effect of multimedia instruction on achievement of college students in AMH 2010 from exploration and discovery to1865. A non-equivalent control group design was used. The dependent variable was achievement. The independent variables were learning styles method of instruction, and visual clarifiers (notes). The study was conducted using two history sections from Palm Beach Community College, in Boca Raton, Florida, between August and December, 1998. Data were obtained by means of placement scores, posttests, the Productivity Environmental Preference Survey (PEPS), and a researcher-developed student survey. Statistical analysis of the data was done using SPSS statistical software. Demographic variables were compared using Chi square. T tests were run on the posttests to determine the equality of variances. The posttest scores of the groups were compared using the analysis of covariance (ANCOVA) at the .05 level of significance. The first hypothesis there is a significant difference in students' learning of U.S. History when students receive multimedia instruction was supported, F = (1, 52)= 688, p < .0005, and F = (1, 53) = 8.52, p < .005for Tests 2 and 3, respectively. The second hypothesis there is a significant difference on the effectiveness of multimedia instruction based on students' various learning preferences was not supported. The last hypotheses there is a significant difference on students' learning of U.S. History when students whose first language is other than English and students who need remediation receive visual clarifiers were not supported. Analysis of covariance (ANCOVA) indicated no difference between the groups on Test 1, Test 2, or Test 3: F (1, 4 5)= .01, p < .940, F (l, 52) = .77, p < .385, and F (1,53) =.17, p > .678, respectively, for language. Analysis of covariance (ANCOVA) indicated no significant difference on Test 1, Test 2, or Test 3, between the groups on the variable remediation: F (1, 45) = .31, p < .580, F (1, 52) = 1.44, p < .236, and F (1, 53) = .21, p < .645, respectively.