Current dissolution apparatuses require several hundred milligrams of sample per trial, measure dissolution rate indirectly via concentration sampling, and cannot maintain sink conditions throughout the duration of a test. This work describes a novel dissolution testing methodology developed using a commercial quartz crystal microbalance (QCM) system to measure dissolution rates of drugs while overcoming the limitations of current dissolution methods. The apparatus was characterized for a sample drug system of benzoic acid dissolved using a dissolution medium of deionized water at flow rates of 1000, 100, 50, and 10 &mgr;L/min. Using an analysis method that combines the responses of resonance frequency and resistance of the quartz crystal during dissolution, the dissolution rate of benzoic acid was found to be 4.029 ± 0.743, 2.026 ± 0.913, 1.565 ± 0.349, and 1.060 ± 0.103 % mass/s, for each flow rate, respectively. The QCM dissolution apparatus method can be used to measure drug dissolution directly by quantifying mass loss (rather than indirectly via concentration changes as with current methods), reduce sample sizes compared with current methods by three orders of magnitude onto the microgram scale, and maintain sink conditions throughout the duration of the test.

Polyamines are ubiquitously present in all living cells. The abnormal metabolism of polyamines that is associated with certain types of cancers has been the focus of several investigations. Enzymes that are involved in the transacetylation of polyamines have been studied extensively, so as to develop inhibitors of these enzymes which may be used as drugs in cancer therapy. Based on indirect evidence, the nuclear spermidine acetyltransferase has been thought to be a critical enzyme that is associated with genetic derepression leading to cancerous growth. In the present study a novel, rapid, sensitive and highly reproducible radio chemical procedure has been developed for assaying spermidine (polyamine) acetylation. The study contains data showing range of linearity of the procedure, percent product recovery, as well as low interference from the unreacted acetyl coenzyme A. Rat liver nuclear spermidine acetyltransferase has been purified using the biochemical procedures annmonium sulfate precipitation, DEAE chromatography, Hydroxyapatite chromatography, Diaminobutyl agarose chromatography and Polyacrylamide P-300 gel filtration. The enzyme obtained at the end of such procedures was found to be essentially homogeneous as seen on native gel electrophoresis. The purified enzyme has been shown to have an isoelectric point of 5.2. Bicine and Hepes were found to be more suitable as buffering species for good enzyme activity. The enzymatic reaction velocity was found to increase with temperature upto 36$\sp\circ$C and was found to increase linearly up to four minutes under non limiting conditions in the presence of 20% glycerol. Using the purified enzyme it has also been established that of the three nuclear polyamines, spermidine is the preferred substrate. The apparent Km for acetyl Co A with spermidine as substrate was found to be about 5 mM. The purified enzyme does acetylate histones. All the substrate analogs containing aminobutylamino group are acetylated by the enzyme.

The purpose of the study was to provide information on factors influencing the choice of an academic major and demographic characteristics of students enrolled in baccalaureate degree programs administered by home economics units in the California State University system. Specific objectives of the study were: (1) to analyze the relative importance of reasons which influence students' choice of an area of study or major and the sources of information used in the decision process and (2) to compare the students' responses on the basis of area of study, gender, age, ethnicity, enrollment status, and marital status. The majority of the students were single, White, females between the ages of 18 and 24. Approximately 80 percent of the respondents represented three of seven areas of study: food and nutrition, interior design, and textiles/clothing/merchandising. Two-thirds of the students had changed their majors one or more times. The most frequently cited last major was business. Respondents rated the reasons for choosing an area of study "moderate" to "extremely high" in importance; ratings assigned to the information sources were "extremely low importance" to "moderate importance." Statistically significant differences in the mean importance scores were found for students grouped by ethnicity and area of study. However, there was no relationship between the means and the background variables age, marital status, and enrollment status. Students are influenced by a variety of factors when choosing an academic program. More emphasis is placed on personal reasons including interest in the program and personal skills and career-related factors, including preparation for a career and job opportunities, than factors identified as service and experiential. The college catalog is the most important source of information. In general, people are of greater importance as information sources than media items. Recommendations for recruitment strategies include: develop on- and off-campus programs designed to stimulate interest in the home economics areas of study, implement a career development plan, coordinate the academic unit's recruitment plan with the university plan, and intensify public relations activities directed towards the university, public, and professional communities. (Abstract shortened with permission of author.)

The aryl hydrocarbon receptor (AHR) is a ligand-activated signaling molecule which is involved in diverse biological functions ranging from cancer metastasis to immune regulation. This receptor forms a cytoplasmic complex with Hsp90, p23, and XAP2. We have previously reported that down-regulation of p23 triggers degradation of the AHR protein, uncovering a potentially dynamic event which controls the cellular AHR levels without ligand treatment. Here we investigate the underlying mechanisms for this p23 effect using wild-type HeLa and the p23 knockdown HeLa cells. Reduction of the Hsp90 and XAP2 contents, however, did not affect the AHR protein levels, implying that this p23 effect on AHR is more than just alteration of the cytoplasmic complex dynamics. Association of p23 with Hsp90 is not important for the modulation of the AHR levels since exogenous expression of p23 mutants with modest Hsp90-binding affinity effectively restored the AHR message and protein levels. The protein folding property of p23 which resides at the terminal 50-amino acid region is not involved for this p23 effect. Results from our interaction study using the affinity purified thioredoxin fusion proteins and GST fusion proteins and isothermal titration calorimetry showed that p23 directly interacts with AHR and the interaction surface lies within AHR amino acid 1–216 and p23 amino acid 1–110. Down-regulation of the p23 protein content promotes the ubiquitination of AHR, indicating that p23 protects AHR from the ubiquitin-meditated protein degradation. However, the increased ubiquitination is not through the small ubiquitin-like modifier (SUMO) signaling pathway. Troubleshooting and optimization were paramount for understanding and evaluating the p23 and AHR interaction. Specifically, the p23 mutant purification, p23: Hsp90 interaction, transient transfection, p23: AHR assay, and ITC study were phases of this research that required extensive time and critical thinking. These topics were further detailed to outline the specific problems encountered and the various steps taken to alleviate or optimize these issues.

Sustained release of nitrofurantoin (NFT) from microspheres of propylene glycol monostearate (PGM) and of PGM and ethoxylated stearyl alcohol (ESA) prepared by the meltable dispersion and cooling process was investigated. The microspheres (30-850 mu) were nonsticky, discrete and free flowing. Both the rate and extent of in vitro release of NFT (from NFT-PGM microspheres in distilled water at 37 degrees C under constant agitation at 50 rpm) declined with decreasing NFT/PGM ratio. The effect of incorporating ESA over the range of 0.01 to 0.05% w/w of PGM in formulations with NFT/PGM ratios of 1:1, 1:1.5 and 1:4, studied under similar experimental conditions revealed that NFT release was maximum in the range of 0.02 to 0.035% ESA. The effect of pH on NFT release from microspheres with 0.03% ESA and without ESA at NFT/PGM ratios of 1:1 and 1:4, was investigated in buffer solutions at pH values of 1.2, 5.8 and 7.2. The pH-dependent solubility and dissolution of NFT and PGM, in addition to NFT/PGM ratio, were found to control the rate and extent of NFT release. Both scanning electron photomicrography and contact angle measurements suggested that about 0.03% ESA was critical for the formulations studied. The in vitro evaluation of adhesion of various polymers to rabbit stomach tissue was investigated. The polymers, CLD, ACDISOL, polycarbophil and calcium polycarbophil were investigated for potential use as bioadhesives. The modified balance method developed and used to evaluate the polymers adhesion to rabbit stomach tissue in vitro at different pH levels was reproducible and could detect change in adhesive force as little as 10 mg weight. Maximum adhesion for polymers CLD and polycarbophil was observed at pH 5.8, while that of ACDISOL was at pH 7.2. The polymer, calcium polycarbophil, showed essentially no adhesion at all. The results revealed that CLD was superior and ACDISOL was inferior to polycarbophil under all three pH conditions investigated. In vitro release studies of the drug from microspheres mixed in various proportions with bioadhesive polymer CLD in phosphate buffer at pH 5.8 indicated that the presence of the polymer did not significantly hinder the drug release. (Abstract shortened with permission of author.)

Training in independent and age-appropriate leisure activities is part of a comprehensive program of active treatment for developmentally disabled adults. Increased leisure skills have been shown to reduce a variety of problem behaviors, enhance a variety of useful skills, and allow the developmentally disabled to assimilate into more normalized settings. However, the developmentally disabled individual's engagement in leisure activities is often restricted due to such things as their own skill deficits, as well as limited availability of materials. This study investigated the effects of two training methods on the leisure behavior of 16 institutionalized severely and profoundly developmentally disabled adults. It was demonstrated that teaching subjects, not only how to use leisure materials, but to self-initiate leisure activity, resulted in significantly more frequent and sustained independent leisure activity than teaching subjects only how to use leisure materials. Data on subjects' videotaped leisure behaviors were collected during Baseline, six days of sessions over two weeks, where subjects were exposed to, but not prompted to use, six different leisure activities. Overall ranks during Baseline were used to assign subjects to two equal treatment groups. Target subjects were taught to self-initiate leisure with a complete task analysis of the activities. The complete task analysis included the entire functional routine of taking out, using (curriculum skills), and putting away materials. Curriculum Instruction subjects were trained only in the use of the materials. The model for training both groups was based on the Behavior Skills Rating Scale. Training sessions were held on 27 days over six weeks. This was followed by six days of Post-training Observation with conditions identical to Baseline. The significance of the difference between groups' subjects' Post-training rankings were determined using the Mann-Whitney U. All analyses utilized two-tailed tests, with significance set at p (greater then) .05. Overall, Target group subjects ranked significantly higher than CI subjects during Post-training Observation. In addition, they ranked significantly higher in the number of sessions with initiated activity; latency before initiating activity; and sustained leisure activity. There was no significant difference in the supplemental skills of taking out and putting away materials.

In the present study, a 8 x 4 mm biodegradable device was formulated using poly(ortho ester) and metronidazole for treatment of periodontitis. Investigation focussed upon determination of formulation parameters in the form of drug (metronidazole) and adjuvant concentrations (oleic acid and palmitic acid) and device thickness necessary to achieve constant release of 0.6 μg/hr over a period of 7 days and complete degradation of the device over a period of 11 to 13 days. Presence of oleic or palmitic acid influenced the release and erosion profile considerably. Thickness of the device did not have significant influence on the drug release. The DSC and NMR studies indicated absence of interaction between drug and polymer. Computer optimization studies indicate that the optimum formulation for 7 day constant drug delivery and disappearance in 13 days should contain 0.28% w/w of oleic acid and 5.26% w/w of metronidazole at the thickness of 400-450 or 500-550 μm. This is in close agreement with the optimum formulation which was obtained with the experimental data.

The phenylhydrazine-induced erythropoietic mouse spleen is used as a model system to demonstrate the relationship between tissue growth and polyamine metabolism. Phenylhydrazine produced significant changes in spleen weights, hematocrits and reticulocyte counts in Swiss-Webster mice. The average spleen weight went up from a control of 155 mg to 875 mg at 96 hours after phenylhydrazine administration, while a 49% reduction in the value of hematocrit was observed at 72 hours. Reticulocyte counts in peripheral blood went from 0.8 to 58% at 168 hours after treatment with phenylhydrazine. Phenylhydrazine at a dose of 40 mg/kg produced significant increases in the levels of putrescine, spermidine and spermine with maxima reached within 72 hours. The levels of N$\sp1$-acetylspermidine reached a maximum of 2.7-fold compared to control at 96 hours. When the dose of phenylhydrazine was increased to 120 mg/kg, peak levels of acetylated polyamines were reached within 96 hours at which time N$\sp1$-acetylspermidine levels rose to 2.9-fold and N$\sp8$-acetylspermidine levels went from not detectable to detectable levels. the levels of putrescine, spermidine and spermine reached maxima at 96 hours of 289, 1248 and 934 nmoles/g, respectively. DL-$\alpha$-difluoromethylornithine hydrochloride monohydrate (DFMO) inhibited the increases in putrescine levels and potentiated the increases in spermine levels induced by phenylhydrazine, while 7-(N-(3-aminopropyl)amino) heptan-2-one.2HCl (APAH) induced significant increases in the levels of N$\sp8$-acetylspermidine. APAH potentiated the increases in spleen weights induced by phenylhydrazine.

The population pharmacokinetics and pharmacodynamics (PK/PD) of nevirapine (NVP), zidovudine (ZDV), and didanosine (ddI) were evaluated in 432 pediatric patients with HIV, randomized to receive either a double-therapy of ZDV + ddI or NVP + ddI; or triple-therapy of NVP + ZDV + ddI as a substudy of the AIDS Clinical Trials Group Protocol 245 in 2 phases. In phase 1, nonlinear mixed-effect modeling (NONMEM) analysis was employed for population pharmacokinetics (PPK) study for ZDV, ddI and NVP. One-compartment model with first-order input and first-order elimination was fitted to the NVP, ZDV and ddI data. Final PPK models were as follows: ZDV; CL (1/hr, without nevirapine coadministration) = 52.4 × BSA, CL (1/hr, with nevirapine coadministration) = 65.0 × BSA, Vd/F(1) = 116 × BSA, ddI; CL (1/hr) = 73.4 × BSA + 69.9, Vd/F(1) = 132, and NVP; CL (1/hr) = 2.30 × BSA, Vd/F(1) = 120. In phase 2, the relationship between the predicted serum concentrations of ZDV, ddI, and NVP and pharmacodynamic responses were evaluated via S-Plus ® exploratory data analysis. No apparent relationship between average steady-state serum concentrations and pharmacodynamic variables, such as HIV-1 RNA(RNA) levels, CD4 + count was found. However, the responses of RNA level and CD4 + count to the double therapy (ddI/NVP) versus triple therapy (ddI/NVP/ZDV) were significantly different after 4 weeks of therapy ( P = 0.0014 for RNA level at week 4, P = 0.0454 for CD4 + count at week 12). No significantly different responses were found in weight changes ( P > 0.25 at all weeks). Also, the maximum drop of RNA level throughout the treatment period had a strong relationship to the decline slope of RNA at week 4 as follows: Maximum drop of RNA = 3.1139 × RNA decline slope at week 4 - 0.411. Nevirapine dosing regimens were compared using simulation via Trial Simulator™. Both ACTG regimen (body surface area based) and manufacture's regimen (age and weight based) produced similar concentrations at lower end concentration but manufacture's regimen produce higher concentration at upper end with 1000 simulated patients (ACTG regimen; 2150, 3827, and 4992 ng/ml, manufacturer's regimen; 2066, 4130, and 6568 ng/ml, for 10 th , 50 th , and 96 th percentile, respectively). It is suggested to use body surface area based dosing regimen for NVP.

Using a multiple baseline design, this study examined the effect of preferred items in increasing medication knowledge among individuals diagnosed with a mental illness. Participants were asked questions regarding their Haldol medication. After baseline, participants received the answers and a pharmacy-generated medication profile. During the Repeated Trials intervention, participants were given only verbal feedback. Those who had not reached criterion after 4 weeks entered the Preferred Trials intervention. In this phase, participants received a high, medium, or low preferred item contingent on the number of correct answers. All participants increased their number of correct answers. Although the effects of a contingent preferred item were mixed, this study showed that information regarding medications can be learned with minimal staff intervention.