Therapeutic Potential of Dietary Polyphenols

The chapter summarizes available research on polyphenols and the potential for polyphenol based therapeutics. Polyphenols have the potential to be used in a multi-target fashion therapeutically. The majority of the polyphenol benefits appear to share positive effects across multiple disease states including inflammatory diseases, diseases of metabolic dysregulation and cancer. The reviewed literature includes human, animal and cell culture based studies. Selected mechanisms within each disease state are highlighted including interleukin inflammatory markers, NF-κB, acetyl-CoA concentration regulation of metabolism, and p-glycoprotein multidrug efflux pump associated with cancer treatment failures. Reviewed studies discuss polyphenols inhibiting transcription factors that control expression on inflammatory factors as well as activating other transcription factors that increase expression of enzymes protective of oxidative damage. Levels of metabolic regulatory enzymes are also affected positively by polyphenol addition through epigenetic modifications. Epigenetic modifications affecting cancer development and progression appear positively affected by polyphenol treatment. Additionally, oxidative damage protection of normal cells can be achieved by polyphenol treatment thus limiting chemotherapeutic damage. Upon review of the available literature, a strong case for the potential use of polyphenols in therapeutic situations stands out. Potential risks included are that the purity and specific concentrations required to achieve therapeutic benefits without potential side effects need to be examined prior to the adoption of therapeutics

Food-Based PPARγ Ligands

Foods and herbs have long been used medicinally and the interest in natural product therapies have returned in the recent decades. PPARγ is a transcription factor that regulates expression of a variety of metabolic genes. The discovery of full activators of PPARγ have been useful in the treatment of diabetes but are not without side effects. The discovery of food based PPARγ ligands have allowed the exploration of natural treatment of a variety of diseases with potentially fewer side effects due to the ligand based activation rather than full activation. Here we present background on the PPARγ transcription factors and summarize several compounds and the food sources that have demonstrated therapeutic potential for disease states including diabetes, cancer, and cardiovascular disease

Exploring a Laboratory Model of Pharmacogenetics as Applied to Clinical Decision Making

Objective: To evaluate a pilot of a laboratory model for relating pharmacogenetics to clinical decision making. Case Study: This pilot was undertaken and evaluated to help determine if a pharmacogenetics laboratory should be included in the core Doctor of Pharmacy curriculum. The placement of the laboratory exercise in the curriculum was determined by identifying the point in the curriculum where the students had been introduced to the chemistry of deoxyribonucleic acid (DNA) as well as instructed on the chemistry of genetic variation. The laboratory included cytochrome P450 2C19 genotyping relative to the *2 variant. Twenty-four students served as the pilot group. Students provided buccal swabs as the source of DNA. Students stabilized the samples and were then provided instructions related to sample preparation, polymerase chain reaction, and gel electrophoresis. The results were reported as images of gels. Students used a reference gel image to compare their results to. Students then applied a dosing algorithm to make a "clinical decision" relative to clopidogrel use. Students were offered a post laboratory survey regarding attitudes toward the laboratory. Twenty-four students completed the laboratory with genotyping results being provided for 22 students (91.7%). Sixteen students were wild-type (*1/*1), while six students were heterozygous (*1/*2). Twenty-three students (96%) completed the post laboratory survey. All 23 agreed (6, 26.1%) or strongly agreed (17, 73.9%) that the laboratory "had relevance and value in the pharmacy curriculum" Conclusion: The post pilot study survey exploring a laboratory model for pharmacogenetics related to clinical decision making indicated that such a laboratory would be viewed positively by students. This model may be adopted by colleges to expand pharmacogenetics education.   Type: Case Stud

Exploring a Laboratory Model of Pharmacogenetics as Applied to Clinical Decision Making

Objective: To evaluate a pilot of a laboratory model for relating pharmacogenetics to clinical decision making. Case Study: This pilot was undertaken and evaluated to help determine if a pharmacogenetics laboratory should be included in the core Doctor of Pharmacy curriculum. The placement of the laboratory exercise in the curriculum was determined by identifying the point in the curriculum where the students had been introduced to the chemistry of deoxyribonucleic acid (DNA) as well as instructed on the chemistry of genetic variation. The laboratory included cytochrome P450 2C19 genotyping relative to the *2 variant. Twenty-four students served as the pilot group. Students provided buccal swabs as the source of DNA. Students stabilized the samples and were then provided instructions related to sample preparation, polymerase chain reaction, and gel electrophoresis. The results were reported as images of gels. Students used a reference gel image to compare their results to. Students then applied a dosing algorithm to make a "clinical decision" relative to clopidogrel use. Students were offered a post laboratory survey regarding attitudes toward the laboratory. Twenty-four students completed the laboratory with genotyping results being provided for 22 students (91.7%). Sixteen students were wild-type (*1/*1), while six students were heterozygous (*1/*2). Twenty-three students (96%) completed the post laboratory survey. All 23 agreed (6, 26.1%) or strongly agreed (17, 73.9%) that the laboratory "had relevance and value in the pharmacy curriculum" Conclusion: The post pilot study survey exploring a laboratory model for pharmacogenetics related to clinical decision making indicated that such a laboratory would be viewed positively by students. This model may be adopted by colleges to expand pharmacogenetics education.   Type: Case Stud

The Effects of on Blood Glucose Values are Greater than those of Dietary Changes Alone

Eighteen type II diabetics (9 women and 9 men) participated in a 12-week trial that consisted of 2 parts, a 3-week control phase followed by a 9-week experimental phase where half of the subjects received 1000 mg of Cinnamomum cassia while the other half received 1000 mg of a placebo pill. All of the subjects that were in the cinnamon group had a statistically significant decrease in their blood sugar levels with a P -value of 3.915 × 10 -10 . The subjects in the cinnamon group had an average overall decrease in their blood sugar levels of about 30 mg/dL, which is comparable to oral medications available for diabetes. All subjects were educated on appropriate diabetic diets and maintained that diet for the entire 12 week study. Greater decreases in blood glucose values were observed in patients using the cinnamon compared to those using the dietary changes alone

Part 1: A Novel Model for Three-Dimensional Culture of 3T3-L1 Preadipocytes Stimulates Spontaneous Cell Differentiation Independent of Chemical Induction Typically Required in Monolayer

Differences in monolayer and three-dimensional (3D) culture systems have been recognized for several years. Despite the recognized importance of 3D systems, low cost and convenience of monolayer culture are still readily used for metabolic and nutritional studies. Here, we present part 1 of a 2-part series that will highlight (1) a novel and cost-effective model for culturing 3T3-L1 preadipocytes in 3D agarose as well as (2) an initial study showing the successful use of this 3D model for experimental analysis of these cells treated with cinnamon extract while suspended in agarose. In part 1, we provide a full characterization of the model system for the 3T3-L1 cells that demonstrate the functionality and convenience of this system. Importantly, we note spontaneous differentiation to adipocytes while cultured under these methods, independent of chemical induction. We present a 2.5-week time course with rounded cells forming vacuoles as early as 24 hours and accumulation of lipid detectable by Oil Red O stain at 0.5 weeks. Serum selection, lipid volume determination, and cell size are characterized. We conclusively demonstrate adipogenesis based on a peroxisome proliferator-activated receptor γ (PPARγ) detection using immunohistochemistry (IHC) of sections from these 3D cultures. Methods, materials and recommendations are described as well as proposed benefits to the use of this culture system for 3T3-L1 cells