Pharmacology, Toxicology and Environmental Health Commons^™

The Effects Of Eating A High Fat Diet On Sensitivity Of Rats To Methamphetamine-Induced Conditioned Place Preference, Kayla Galindo

Open Access Theses & Dissertations

Eating a high fat diet causes several negative health consequences, including dysfunction to dopamine systems. For example, eating a high fat diet enhances sensitivity of rats to methamphetamine-induced locomotor sensitization. However, it is not known if sensitivity to other (i.e., the rewarding) effects of methamphetamine are similarly enhanced in rats eating a high fat diet. Females are more sensitive than males to the behavioral effects of stimulants in general, and therefore might also be particularly vulnerable to the effects of diet on the rewarding effects of stimulant drugs. To test the hypoThesis that eating high fat chow enhances sensitivity of …

Cyp2d6 Predicts Plasma Donepezil Concentrations In A Cohort Of Thai Patients With Mild To Moderate Dementia., Monpat Chamnanphon, Sorawit Wainipitapong, Teeravut Wiwattarangkul, Phenphichcha Chuchuen, Kunathip Nissaipan, Weeraya Phaisal, Sookjaroen Tangwongchai, Chonlaphat Sukasem, Supeecha Wittayalertpanya, Andrea Gaedigk, Daruj Aniwattanapong, Pajaree Chariyavilaskul

Manuscripts, Articles, Book Chapters and Other Papers

Purpose: Donepezil, a drug frequently used to treat dementia, is mainly metabolized by cytochrome P450 2D6 (CYP2D6). This study investigated the relationships between CYP2D6 genotype and activity scores as well as predicted phenotype of plasma donepezil concentrations in 86 Thai dementia participants.

Materials and methods: CYP2D6 was genotyped using bead-chip technology (Luminex xTAG® v.3). Steady-state trough plasma donepezil concentrations were measured using high-performance liquid chromatography.

Results: Sixteen genotypes were found but the most frequent genotypes detected among our participants were CYP2D6*10/*10 (27.9%) and *1/*10 (26.7%). One-third of the participants had an activity score of 1.25 which predicted that they were …

Comparison Of Centrifugation And Solid Phase Extraction (Spe) Methods Of Sample Preparations In Determination Of Residues Of Drugs Of Abuse In Urine, John Mahugija, Anastazia Wandwi, Kessy Kilulya

Tanzania Journal of Science

Detection of drugs of abuse in urine samples depends on their composition, absorption, distribution, physical and chemical properties, concentrations, elimination properties, and the techniques employed. This study compared the performance of centrifugation and solid phase extraction (SPE) methods in the determination of levels of drugs of abuse and their metabolites in urine samples collected from drug abusers. Analysis was performed using liquid chromatography-tandem mass spectrometry (LC-MS-MS). Calibration was done using both internal and external standards. The recovery values were generally greater in centrifugation method than in SPE method, but the recoveries in both methods were within an acceptable range. Linearity …

Pharmacokinetics And Antiangiogenic Studies Of Potassium Koetjapate In Rats, Seyedeh F. Jafari, Fouad Saleih R. Al-Suede, Ashwaq H.S. Yehya, Mohamed B.K. Ahamed, Armaghan Shafaei, Muhammad Asif, Yasser M. Tabana, Amin M.S.A. Majid, Hussein M. Baharetha

Research outputs 2014 to 2021

© 2020 Purpose: Koetjapic acid is an active compound of a traditional medicinal plant, Sandoricum koetjape. Although koetjapic acid has a promising anticancer potential, yet it is highly insoluble in aqueous solutions. To increase aqueous solubility of koetjapic acid, we have previously reported a chemical modification of koetjapic acid to potassium koetjapate (KKA). However, pharmacokinetics of KKA has not been studied. In this study, pharmacokinetics and antiangiogenic efficacy of KKA are investigated. Methods: Pharmacokinetics of KKA was studied after intravenous and oral administration in SD rats using HPLC. Anti-angiogenic efficacy of KKA was investigated in rat aorta, human endothelial cells …

Ontogeny Related Changes In The Pediatric Liver Metabolome., Christopher M. Wilson, Qian Li, R Gaedigk, Chengpeng Bi, Saskia N. De Wildt, J Steven Leeder, Brooke L. Fridley

Manuscripts, Articles, Book Chapters and Other Papers

Background: A major challenge in implementing personalized medicine in pediatrics is identifying appropriate drug dosages for children. The majority of drug dosing studies have been based on adult populations, often with modification of the dosing for children based on size and weight. However, the growth and development experienced by children between birth and adulthood represents a dynamically changing biological system, with implications for effective drug dosing, efficacy as well as potential drug toxicity. The purpose of this study was to apply a metabolomics approach to gain preliminary insights into the ontogeny of liver function from newborn to adolescent.

Methods: Metabolites …

Rats Genetically Selected For High Aerobic Exercise Capacity Have Elevated Plasma Bilirubin By Upregulation Of Hepatic Biliverdin Reductase-A (Bvra) And Suppression Of Ugt1a1, Terry D. Hinds Jr., Justin F. Creeden, Darren M. Gordon, Adam C. Spegele, Steven L. Britton, Lauren G. Koch, David E. Stec

Pharmacology and Nutritional Sciences Faculty Publications

Exercise in humans and animals increases plasma bilirubin levels, but the mechanism by which this occurs is unknown. In the present study, we utilized rats genetically selected for high capacity running (HCR) and low capacity running (LCR) to determine pathways in the liver that aerobic exercise modifies to control plasma bilirubin. The HCR rats, compared to the LCR, exhibited significantly higher levels of plasma bilirubin and the hepatic enzyme that produces it, biliverdin reductase-A (BVRA). The HCR also had reduced expression of the glucuronyl hepatic enzyme UGT1A1, which lowers plasma bilirubin. Recently, bilirubin has been shown to activate the peroxisome …

David S. Miller: Scientist, Mentor, Friend--A Tribute And Thank You, Björn Bauer, J. Larry Renfro, Karl J. Karnaky, Rosalinde Masereeuw, Gert Fricker, Ron E. Cannon, Anika M. S. Hartz

Pharmaceutical Sciences Faculty Publications

David S. Miller was Acting Scientific Director of the Division of Intramural Research at the National Institute of Environmental Health Sciences, National Institutes of Health, and Head of the Intracellular Regulation Group in the Laboratory of Toxicology and Pharmacology before he retired in 2016. David received his Ph.D. in biochemistry from the University of Maine in 1973. David was a Group Leader at the Michigan Cancer Foundation before joining the NIEHS in 1985. His research covered a wide range from renal excretory transport mechanisms to regulation of transporters at the blood-CSF and blood-brain barriers, from fish, amphibians and birds to …

Develop A High-Throughput Screening Method To Identify C-P4h1 (Collagen Prolyl 4-Hydroxylase 1) Inhibitors From Fda-Approved Chemicals, Shike Wang, Kuo-Hao Lee, Nathália Victoria Araujo, Chang-Guo Zhan, Vivek M. Rangnekar, Ren Xu

Pharmaceutical Sciences Faculty Publications

Collagen prolyl 4-hydroxylase 1 (C-P4H1) is an α-ketoglutarate (α-KG)-dependent dioxygenase that catalyzes 4-hydroxylation of proline on collagen. C-P4H1-induced prolyl hydroxylation is required for proper collagen deposition and cancer metastasis. Therefore, targeting C-P4H1 is considered a potential therapeutic strategy for collagen-related cancer progression and metastasis. However, no C-P4H1 inhibitors are available for clinical testing, and the high content assay is currently not available for C-P4H1 inhibitor screening. In the present study, we developed a high-throughput screening assay by quantifying succinate, a byproduct of C-P4H-catalyzed hydroxylation. C-P4H1 is the major isoform of collagen prolyl 4-hydroxylases (CP4Hs) that contributes the majority prolyl 4-hydroxylase …

The Association Between Medication Use And Gait In Adults With Intellectual Disabilities, S. Maas, D. A.M. Festen, Thessa I.M. Hilgenkamp, A. Oppewal

Physical Therapy Faculty Research

Background: Adults with intellectual disabilities (ID) often have polypharmacy and often use antipsychotics. Both polypharmacy and antipsychotics have a negative effect on gait in the general population, but this has not been studied in adults with ID. These negative effects may add to pre‐existing gait disturbances in adults with ID and increase the risk for adverse health outcomes in this population. Therefore, the aim of this study is to investigate the difference in gait parameters between adults with ID with and without polypharmacy and between adults with ID using and not using antipsychotics. Method: The gait parameters of 31 participants …

Corrigendum To “Physicochemical Analysis And Nonisothermal Kinetic Study Of Sertralineelactose Binary Mixtures”, Farnaz Monajjemzadeh

Journal of Food and Drug Analysis

No abstract provided.

Corrigendum To “Shenmai-Yin Decreased The Clearance Of Nifedipine In Rats: The Involvement Of Time-Dependent Inhibition Of Nifedipine Oxidation”, Yune- Fang Ueng

Journal of Food and Drug Analysis

No abstract provided.

Corrigendum To “The Time-Dependent Effects Of St John's Wort On Cytochrome P450, Uridine Diphosphate-Glucuronosyltransferase, Glutathione S-Transferase, And Nad(P)H-Quinone Oxidoreductase In Mice”, Yune- Fang Ueng

Journal of Food and Drug Analysis

No abstract provided.

Corrigendum To “Effects Of Aqueous Extract Of Ruta Graveolens And Its Ingredients On Cytochrome P450, Uridine Diphosphate (Udp)-Glucuronosyltransferase, And Reduced Nicotinamide Adenine Dinucleotide (Phosphate) (Nad(P)H)-Quinone Oxidoreductase In Mice”, Yune- Fang Ueng

Journal of Food and Drug Analysis

No abstract provided.

Acarbose Attenuates Migration/Proliferation Via Targeting Microrna-143 In Vascular Smooth Muscle Cells Under Diabetic Conditions, Wei-Yuan Chuang, Meng-Hsun Yu, Tsung-Yuan Yang, Kuei-Chuan Chan, Chau-Jong Wang

Journal of Food and Drug Analysis

Acarbose (an a-glucosidase inhibitor) has been demonstrated to reduce the progression of atherosclerosis without affecting serum levels of glucose in rabbits fed a high cholesterol diet. The main focus of recent atherosclerosis studies has been microRNA targets. However, the mechanism by which acarbose targets miRNA-mediated atherosclerosis remains unclear. This study aimed to evaluate the effect of acarbose on microRNA-related regulation of rat aortic vascular smooth cell line (A7r5 cell) migration and proliferation induced by diabetic conditions. We reported that acabose exhibit significantly inhibits proliferative and cell migration abilities in A7r5 cells. The expression of protein and levels of mRNA were …

Effect Of 6,7-Dimethoxy-2,2-Dimethyl-2h-Chromene (Agerarin) On The Recovery Of Filaggrin Expression Through Targeting Of Janus Kinases In The Inflammatory Skin, Sung Shin Ahn, Young Han Lee, Hyunjin Yeo, Youngshim Lee, Do Sik Min, Yoongho Lim, Soon Young Shin

Journal of Food and Drug Analysis

Filaggrin (FLG) is a structural component of the stratum corneum that is essential for maintaining the barrier function of the skin and for the formation of natural moisturizing factors. 6,7-Dimethoxy-2,2-dimethyl-2H-chromene (Agerarin) is a bioactive compound derived from Ageratum houstonianum, a plant that is used as a traditional medicine to treat skin diseases. This study aimed to evaluate the effect of agerarin on skin inflammation in a dinitrochlorobenzene (DNCB)-induced atopic dermatitis mouse model. We found that the topical administration of agerarin ameliorates atopic dermatitis-like skin lesions. We also showed that agerarin restores the reduced filaggrin (FLG) expression in …

Biologically-Guided Isolation Of Natural Lead Antithyroid Drug From Medicago Sativa L. Sprouts And Its Toxic Profile In Comparison With Propylthiouracil, Reham S. Ibrahim, Nesrine S. El-Mezayen, Asmaa Khairy, Hala H. Zaatout, Hala M. Hammoda, Aly M. Metwally

Journal of Food and Drug Analysis

Hyperthyroidism is a common endocrine disorder associated with increased risk of cardiovascular complications and mortality. Although antithyroid drugs (ATDs) are approved as first line option for many hyperthyroidism cases, including pregnancy and childhood, they exert significant toxic profile. Medicago sativa L. (alfalfa) also called “The father of all food” was among the diet consumed by mares that gave birth to foals with congenital hypothyroidism. Since, greenfeed was accused for the development of such condition, alfalfa may possess constituents with promising antithyroid potential that could be a valuable substitute for the conventional ATDs. The current work was designed to identify the …

Establishment Of Indirect Competitive Enzyme Linked Immunosorbent Assay For The Detection Of Platycodin D In Radix Platycodonis, Shuai Luo, Yanfei He, Hongxiang Sun

Journal of Food and Drug Analysis

Platycodin D (PD) has been used as the quality control marker of Radix Platycodonis for its high content and various pharmacological properties. In this study, a specific polyclonal antibody against PD (PD–pAb) was developed, and PD–pAb-based indirect competitive enzyme-linked immunosorbent assay (icELISA) was established for the detection of PD in Radix Platycodonis. The 50% inhibition concentration (IC₅₀) of PD was 2.70 μg/mL and the linearity range for PD was from 0.064 μg/mL to 100 μg/mL. No cross reactivity with PD–pAb was found in five PD analogs except for PD2 (0.93%). The average recovery of PD by icELISA was …

Quantification Of Adenosine Mono-, Di- And Triphosphate From Royal Jelly Using Liquid Chromatography - Tandem Mass Spectrometry, Wan-Rou Liao, Jen-Pang Huang, Sung-Fang Chen

Journal of Food and Drug Analysis

Nucleotides are composed of nitrogen bases, ribose units and phosphate groups. Adenine (Ade), adenosine monophosphate (AMP), adenosine diphosphate (ADP) and adenosine triphosphate (ATP) all play important roles in physiological metabolism. Royal jelly, a secretion produced by worker bees, contains a variety of natural ingredients and several studies have shown that royal jelly can serve as a source of nutrition for humans. In this study, a rapid and effective LC/MS method coupled with pre-processing methods was developed and validated for the accurate quantification of Ade, AMP, ADP and ATP in royal jelly. To achieve the best extraction efficiency, two pretreatment methods, …

Lipophilized Epigallocatechin (Egc) And Its Derivatives: Inhibition Of Oxidation Of Β-Carotene–Linoleate Oil-In-Water Emulsion And Dna Strand Scission, Priyatharini Ambigaipalan, Won Young Oh, Fereidoon Shahidi

Journal of Food and Drug Analysis

Tea epigallocatechin (EGC) was acylated with selected fatty acids, namely propionic acid [C3:0], caprylic acid [C8:0], lauric acid [C12:0], stearic acid [C18:0] and docosahexaenoic acid (DHA; C22:6 n-3). Antioxidant activity of EGC and its lipophilized derivatives were examined in various food (β-carotene–linoleate oil-in-water emulsion and bulk oil) and biological (supercoiled DNA and LDL) systems in vitro in order to evaluate the effect of increased lipophilicity on their antioxidant capacity. Lipophilized EGC derivatives were more effective in β-carotene–linoleate oil-in-water emulsion and bulk oil than their parent EGC molecule. Meanwhile, EGC and its derivatives showed more than 60 …

Development Of An Lc-Esi-Ms/Ms Method For Determination Of A Novel Pyrrolomycin (Mp-1) And Application To Pre-Clinical Adme Studies, Wafaa N. Aldhafiri

Theses & Dissertations

A rapid, selective, and sensitive liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method was developed and validated for quantitation of a novel Pyrrolomycin (MP-1) in mouse plasma. MP-1 was extracted from plasma utilizing a structural analog (PL-3) as the internal standard (IS). Analyte separation was achieved using a Waters Acquity UPLC®BEH C18 column (1.7 µm, 100 x 2.1 mm) protected with Acquity UPLC C18 guard column. Mobile phase consisted of 0.1% acetic acid in water (10%) and methanol (90%) at a total flow rate of 0.25 mL/min. The mass spectrometer was operated at unit resolution in the multiple reaction …

Isolation, Structure Elucidation, And Synthesis Of Natural Products From Marine Cyanobacteria, Keren Solomon

Electronic Theses and Dissertations

This thesis describes the isolation, structure elucidation, and synthesis of natural products from marine cyanobacteria. A crude extract from a cyanobacterium collected in Curacao showed selective affinity for the dopamine D₅ receptor in a screen against a panel of CNS receptors. Due to the high similarity of the D₅ and D₁ receptor, to date there are no known ligands that differentiate them. Attempts to purify the compound responsible for this affinity led to the isolation of the known compound caylobolide A. A second extract from a cyanobacterium collected in Panama underwent bioassay-guided fractionation and yielded the novel …

Innovative Approaches In The Discovery Of Aquatic Mycobacteriophages, Janis H. Doss

Biomedical Sciences Theses & Dissertations

Bacteriophages (phages), viruses that infect bacteria, have many applications in medicine, agriculture, molecular biology, and other fields. As antibiotic resistance becomes an increasing problem, interest in phages has grown. The traditional techniques of phage discovery are successful for some phages, but others require modified procedures to achieve detectable host infection.

Mycobacterium is a diverse bacterial genus characterized by a unique cell wall containing mycolic acids, which aids in survival and pathogenesis. The aims of the present research were to isolate mycobacteriophages, use bioinformatics techniques to analyze mycobacterial prophages, and combine genetic analysis with multi-well plate host range studies to identify …

N-Acetyltranserase 2 (Nat2) Genotype Polymorphism In Cryopreserved Human Hepatocytes And Chinese Hamster Ovary (Cho) Cells., Mariam Refaat Zaky Habil

Electronic Theses and Dissertations

Arylamine N-acetyltransferases, NAT1 and NAT2, catalyze the detoxification and/or activation of drugs and aromatic amine carcinogens. Single nucleotide polymorphisms or SNPs result in different human NAT2 genotypes thus dividing the population into rapid, intermediate, and slow acetylators. We hypothesize allelic variants of NAT2 genotype will decrease levels of N-acetylation, cytotoxicity, oxidative stress, DNA adduct formation, and mutagenesis compared to the reference allele NAT2*4. Cryopreserved human hepatocytes expressing different NAT2 genotypes and NER-deficient Chinese hamster ovary (CHO) cells transfected with human CYP1A2 and human NAT2*4, NAT2*5B or NAT2*7B have been used to investigate N-acetylation of different xenobiotics. In …

Introduction To Dr. Jerzy Leszczynski, P. Fu

Journal of Food and Drug Analysis

[No abstract available]

Codonopsis Javanica Root Extracts Attenuate Hyperinsulinemia And Lipid Peroxidation In Fructose-Fed Insulin Resistant Rats, K.-N. Chen, W.-H. Peng, C.-W. Hou, C.-Y. Chen, H.-H. Chen, C.-H. Kuo, M. Korivi

Journal of Food and Drug Analysis

From ancient times, Dǎngshēn (Codonopsis javanica) has been used in Chinese traditional medicine. In this study we investigated the anti-hyperinsulinemia and antioxidant properties of C. javanica root extracts in a rat model of insulin resistance (IR), induced by chronic fructose feeding. Twenty-four Sprague–Dawley rats were randomized into control, fructose-treated (10%, w/v), and fructose then C. javanica (Fru + Cod)-treated groups. After 8 weeks fructose feeding, increased fasting serum insulin levels (2.6 ± 0.45 μg/L) and insulin area under the curve confirmed the IR (p < 0.001). However, C. javanica treatment to fructose-fed rats significantly attenuated the hyperinsulinemia with correspondingly improved glucose tolerance. Weight gain in Fru + Cod group was comparably (p < 0.01) lower than in the fructose-fed group. Furthermore, IR-induced increased hepatic lipid peroxidation, as demonstrated by elevated malondialdehyde levels, were significantly (p < 0.001) alleviated by C. javanica treatment. These findings reveal that chronic fructose intake may facilitate IR and oxidative damage, which could be eradicated by improved antioxidant status. Accordingly, we found that C. javanica treatment significantly improved the antioxidant enzyme activities, including superoxide dismutase, glutathione peroxidase and glutathione reductase in the liver. These findings that fructose-induced hyperinsulinemia and associated oxidative stress could be attenuated by C. javanica root extracts. © 2013

Evaluating The Urate-Lowering Effects Of Different Microbial Fermented Extracts In Hyperuricemic Models Accompanied With A Safety Study, R.-J. Chen, M.-H. Chen, Y.-L. Chen, C.-M. Hsiao, H.-M. Chen, S.-J. Chen, M.-D. Wu, Y.-J. Yech, G.-F. Yuan, Y.-J. Wang

Journal of Food and Drug Analysis

Uric acid (UA) is an end product of purine metabolism by the enzyme xanthine oxidase (XOD). Hyperuricemia is characterized by the accumulation of serum UA and is an important risk factor for gout and many chronic disorders. XOD inhibitors or uricase (catalyzes UA to the more soluble end product) can prevent these chronic diseases. However, currently available hypouricemic agents induce severe side effects. Therefore, we developed new microbial fermented extracts (MFEs) with substantial XOD inhibition activity from Lactobacillus (MFE-21) and Acetobacter (MFE-25), and MFE-120 with high uricase activity from Aspergillus. The urate-lowering effects and safety of these MFEs were evaluated. …

Lactobacillus Pentosus Gmnl-77 Inhibits Skin Lesions In Imiquimod-Induced Psoriasis-Like Mice, Y.-H. Chen, C.-S. Wu, Y.-H. Chao, C.-C. Lin, H.-Y. Tsai, Y.-R. Li, Y.-Z. Chen, W.-H. Tsai, Y.-K. Chen

Journal of Food and Drug Analysis

Psoriasis, which is regarded as a T-cell-mediated chronic inflammatory skin disease, is characterized by hyperproliferation and poor differentiation of epidermal keratinocytes. In this study, we aimed to determine the in vivo effect of a potentially probiotic strain, Lactobacillus pentosus GMNL-77, in imiquimod-induced epidermal hyperplasia and psoriasis-like skin inflammation in BALB/c mice. Oral administration of L. pentosus GMNL-77 significantly decreased erythematous scaling lesions. Real-time polymerase chain reaction showed that treatment with L. pentosus GMNL-77 significantly decreased the mRNA levels of proinflammatory cytokines, including tumor necrosis factor-alpha, interleukin (IL)-6, and the IL-23/IL-17A axis-associated cytokines (IL-23, IL-17A/F, and IL-22) in the skin of …

Long-Term Feeding Of Red Algae (Gelidium Amansii) Ameliorates Glucose And Lipid Metabolism In A High Fructose Diet-Impaired Glucose Tolerance Rat Model, H.-C. Liu, C.-J. Chang, T.-H. Yang, M.-T. Chiang

Journal of Food and Drug Analysis

This study was designed to investigate the effect of Gelidium amansii (GA) on carbohydrate and lipid metabolism in rats with high fructose (HF) diet (57.1% w/w). Five-week-old male Sprague-Dawley rats were fed a HF diet to induce glucose intolerance and hyperlipidemia. The experiment was divided into three groups: (1) control diet group (Con); (2) HF diet group (HF); and (3) HF with GA diet group (HF + 5% GA). The rats were fed the experimental diets and drinking water ad libitum for 23 weeks. The results showed that GA significantly decreased retroperitoneal fat mass weight of HF diet-fed rats. Supplementation …

Determination Of Urea In Milk Based On N-Bromosuccinimide–Dichlorofluorescein Postchemiluminescence Method, F. Nie, N. Wang, P. Xu, J. Zheng

Journal of Food and Drug Analysis

A new postchemiluminescence (PCL) reaction was observed when urea was injected into the reaction mixture after the CL reaction of N-bromosuccinimide and dichlorofluorescein. A possible reaction mechanism was proposed based on the studies of the CL kinetic characteristics, CL spectra, fluorescence spectra, and other experiments. A new flow injection CL method for the determination of urea was established based on the PCL reaction. The relative standard deviation for the determination of urea was 1.3% (n = 11, c = 5.0 × 10−8 g/mL). The CL intensity responded linearly to the concentration of urea in the range 2.0 × 10−9–1.0 × …

Regulatory Aspects Of Living Biological Material, S.-C. Jong, J.M. Birmingham

Journal of Food and Drug Analysis

Any living biological material is, in effect, a biotechnology factory complete with sophisticated process designs and its own source of venture capital. Biotechnology is the application of living material and its process system to obtain useful products or services. It is not limited to the recent developments in recombinant DNA techniques, monoclonal antibodies, and related processes and products, aspects with which it is most often identified, but includes the manufacture of nonrecombinant biological material, such as microorganisms and plants and animals from traditional breeding methods; biologically active compounds; and a variety of foods and drugs. Due to complex economic, social, …