A Pilot Study on the Use of Lecture Tools to Enhance the Teaching of Pharmacokinetics and Pharmacodynamics

Pharmacokinetics and pharmacodynamics are essential topics contained within the medical curriculum and are highly amenable to active-learning approaches. In this pilot study, we incorporated Lecture Tools, a cloud-based audience response system, into a lecture-based graduate course. Lecture Tools was used by both the instructors and the students during peer presentations. Advantages noted by the instructors include the versatility of the questions that can be presented and the ease with which student assessment can be conducted. Student surveys revealed that, overall, the use of Lecture Tools enhanced student attentiveness and engagement and facilitated student participation in questions and answers. Some disadvantages were observed and include the increased time required for lecture presentations. In summary, our results indicate that Lecture Tools can be effectively used in a medical education setting

Effects of the anticarcinogen indole-3-carbinol on Xenobiotic metabolizing enzymes in rainbow trout

Indole-3-carbinol (I3C) inhibits chemically induced tumor formation in rodents and rainbow trout. This study examines the effect of I3C and its analog, indole-3-acetonitrile (I3N) on xenobiotic-metabolizing enzyme systems. The modulation of these enzyme systems have been shown to have significant effects on the interaction of chemical carcinogens and cellular constituents. Rainbow trout were fed 500, 1000 and 2000 ppm dietary levels of I3C and 50, 500 and 1000 ppm dietary levels of I3N for 8 days. β-napthoflavone (BNF), which is also an effective anticarcinogen in the trout, was fed at a 500 ppm dietary level and was used as a positive LM4b (a cytochrome P-450 isozyme) inducing control. Enzyme activities assayed were: ethoxyresorufin-O-deethylase (EROD), ethoxycoumarin-O-deethylase (ECOD), glutathione S-transferase (GST), and uridine diphosphoglucuronosyl transferase (UDPGT). Total cytochrome P-450 content was determined spectrophotometrically by the CO reduced method. The specific P-450 isozymes, LM2 and LM4b, were detected quantitatively using the western blot method. The BNF diet induced EROD and ECOD activities by an average of 17 fold and 5.5 fold, respectively. Total P-450 content was increased 2-fold; the P-450 isozyme LM4b was induced more than 5-fold, but LM2 content remained unchanged. This diet increased UDPGT activity 1.5-2-fold, but GST activity was not induced by dietary BNF. Neither I3C nor I3N induced the activity levels of the enzymes assayed at any administered dietary levels, which have previously shown to inhibit tumor formation and reduce formation of carcinogen-DNA adducts. Thus, the anticarcinogenic mechanism of I3C may proceed in trout by mechanisms other than enzyme induction. Further experiments on the effect of I3C and I3C acid condensation products (RXN) on in vitro AFB1-DNA binding resulted in a 40% and 48% inhibition of AFB1-DNA binding by I3C and RXN, respectively. Additions of RXN at levels much lower than those estimated to exist in vivo in hepatic tissue resulted in a significant reduction in AFB1-DNA formation suggesting that even small levels of RXN offers protection against the genotoxic effect of AFB1. However, in vitro additions of neither I3C nor RXN had an effect on DNA binding using AFBI-CI₂, an aflatoxin analog that does not require enzymatic activation. These results suggest that the primary mechanism for I3C inhibition of AFB1 induced carcinogenesis may proceed by inhibiton of formation of the ultimate electrophile, i.e. by reversible inhibition of cytochrome P-450

Improvisation as a Teaching Tool for Improving Oral Communication Skills in Premedical and Pre-Biomedical Graduate Students

Objective: To evaluate the relationship between training in theatre improvisation and empathy, communication, and other professional skills. Methods: Undergraduate and graduate students who were participants of a 10-week summer undergraduate research program engaged in theatre improvisation techniques during a 3-hour workshop. In Study #1, a de-identified, self-report questionnaire (known as the Empathy Quotient) was administered prior to and following the workshop. Paired sample 2-tailed t-tests were performed to evaluate pre- and post-test scores. To identify additional benefits of engaging in theatre improvisation techniques, Study #2 was performed. Here, a survey was administered to the participants following their completion of the workshop to assess the impact on their personal growth and professional skills. An additional survey was administered at the end of the 10-week program to evaluate all program activities. Results: Study #1. Paired t-test analyses indicated that pre-test versus post-test Empathy Quotient scores were not significantly different, implying that participation in the theatre improvisation workshop did not impact empathy. Study #2. Survey results indicate that participation in the theatre improvisation workshop encouraged feelings of support by peers and creative thinking as well as increasing communication skills. Conclusion: Incorporating a theatre improvisation workshop into educational programs for pre-medical and pre-biomedical students is of value for enhancing self-confidence, oral communication skills and ability to think creatively

Development of a Course-Based Undergraduate Research Experience to Introduce Drug-Receptor Concepts

Course-based research experiences (CUREs) are currently of high interest due to their potential for engaging undergraduate students in authentic research and maintaining their interest in science, technology, engineering, and mathematics (STEM) majors. As part of a campuswide initiative called STEMCats, which is a living learning program offered to freshman STEM majors at the University of Kentucky funded by a grant from Howard Hughes Medical Institute, we have developed a CURE for freshmen interested in pursuing health care careers. Our course, entitled “Drug–Drug Interactions in Breast Cancer,” utilized a semester-long, in-class authentic research project and instructor-led discussions to engage students in a full spectrum of research activities, ranging from developing hypotheses and experimental design to generating original data, collaboratively interpreting results and presenting a poster at a campus-wide symposium. Student’s feedback indicated a positive impact on scientific understanding and skills, enhanced teamwork and communication skills, as well as high student engagement, motivation, and STEM belonging. STEM belonging is defined as the extent to which a student may view the STEM fields as places where they belong. The results obtained from this pilot study, while preliminary, will be useful for guiding design revisions and generating appropriate objective evaluations of future pharmacological-based CUREs

Current and Emerging Uses of Statins in Clinical Therapeutics: A Review

Statins, a class of cholesterol-lowering medications that inhibit 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, are commonly administered to treat atherosclerotic cardiovascular disease. Statin use may expand considerably given its potential for treating an array of cholesterol-independent diseases. However, the lack of conclusive evidence supporting these emerging therapeutic uses of statins brings to the fore a number of unanswered questions including uncertainties regarding patient-to-patient variability in response to statins, the most appropriate statin to be used for the desired effect, and the efficacy of statins in treating cholesterol-independent diseases. In this review, the adverse effects, costs, and drug–drug and drug–food interactions associated with statin use are presented. Furthermore, we discuss the pleiotropic effects associated with statins with regard to the onset and progression of autoimmune and inflammatory diseases, cancer, neurodegenerative disorders, strokes, bacterial infections, and human immunodeficiency virus. Understanding these issues will improve the prognosis of patients who are administered statins and potentially expand our ability to treat a wide variety of diseases

Exposure to PCB126 During The Nursing Period Reversibly Impacts Early-Life Glucose Tolerance

Polychlorinated biphenyls (PCBs) are persistent environmental organic pollutants known to have detrimental health effects. Using a mouse model, we previously demonstrated that PCB126 exposure before and during pregnancy and throughout the perinatal period adversely affected offspring glucose tolerance and/or body composition profiles. The purpose of this study was to investigate the glucose tolerance and body composition of offspring born to dams exposed to PCB126 during the nursing period only. Female ICR mice were bred, and half of the dams were exposed to either vehicle (safflower oil) or 1 µmole PCB126 per kg of body weight via oral gavage on postnatal days (PND) 3, 10, and 17 (n = 9 per group). Offspring body weight, lean and fat mass, and glucose tolerance were recorded every three weeks. PCB126 treatment did not alter dam nor offspring body weight (p \u3e 0.05). PCB126-exposed male and female offspring displayed normal body composition (p \u3e 0.05) relative to vehicle-exposed offspring. However, both male and female offspring that were exposed to PCB126 during the nursing period had significantly impaired glucose tolerance at 3 and 9 weeks of age (p \u3c 0.05). At 6 and 12 weeks of age, no impairments in glucose tolerance existed in offspring (p \u3e 0.05). Our current study demonstrates that exposure to PCB126 through the mother\u27s milk does not affect short- or long-term body composition but impairs glucose tolerance in the short-term

The aryl hydrocarbon receptor interacts with transcription factor IIB

ABSTRACT The aryl hydrocarbon receptor (AHR) and its DNA binding partner, the AHR nuclear translocator (ARNT), are basic helix-loophelix transcription factors that mediate many of the toxic and carcinogenic effects of polyhalogenated aromatic hydrocarbons. The basic regions of the AHR and ARNT contact the GCGTG recognition site, whereas both their helix-loop-helix domains and periodicity-ARNT-single-minded domains participate in heterodimerization. To delineate the transcription factors that may facilitate DNA binding and transcriptional activation of the AHR/ARNT heterodimer, we questioned whether transcription factor IIB (TFIIB) may interact with either the AHR or ARNT and whether this interaction may affect the ability of the AHR/ARNT complex to bind DNA. Coaffinity precipitation assays demonstrated that both the AHR and ARNT were capable of interacting with TFIIB. Domain mapping experiments revealed that TFIIB interacts with the periodicity-ARNT-singleminded and carboxyl-terminal regions of the AHR. To determine whether the interaction between TFIIB and the AHR may affect DNA binding of the AHR and ARNT complex, we performed gel shift experiments in the absence and presence of TFIIB. The addition of TFIIB significantly increased the formation of the AHR/ARNT DNA binding complex, but only if TFIIB was first allowed to interact with the AHR before the addition of ARNT. These results indicate that TFIIB interacts with the AHR and may stabilize the DNA binding form of the AHR and thereby augment the ability of the AHR/ARNT complex to interact with its DNA recognition site