Pharmacology, Toxicology and Environmental Health Commons^™

A Multi-Analyte Lc-Ms/Ms Method For Screening And Quantification Of Nitrosamines In Sartans, Shu-Han Chang, Ching-Chia Chang, Li-Jing Wang, Wei-Ching Chen, Shu-Yu Fan, Chi-Zong Zang, Ya-Hui Hsu, Mei-Chih Lin, Su-Hsiang Tseng, Der-Yuan Wang

Journal of Food and Drug Analysis

An incident of sartan medicine contamination was notified by Europe in June 2018. The contaminant was identified as a probable carcinogenic nitrosamine and the recalls of sartan medicines were soon made. Since then, more nitrosamine contaminants in sartan medicines were reported. To broaden the applicability and variety in nitrosamine determination, a multi-analyte method is required. In this study, a feasible and sensitive multi-analyte LC-MS/MS method for determination of 12 nitrosamines in sartans was established, where the active pharmaceutical ingredients and final products merchandised in Taiwan were also examined. Chromatographic separation was achieved on an Xselect® HSS T3 column (15 cm …

Anti-Inflammatory Effects Of Peptides From A Marine Algicolous Fungus Acremonium Sp. Ntu492 In Bv-2 Microglial Cells, George Hsiao, Shih-Wei Wang, Yin-Ru Chiang, Wei-Chiung Chi, Yueh-Hsiung Kuo, Do Anh Phong, Chia-Yu Chen, Tzong-Huei Lee

Journal of Food and Drug Analysis

Located in tropical and subtropical region, Taiwan is an island with high algal species diversity. In this study, a number of fungal strains were isolated from marine macroalgae collected from northeastern intertidal zone of Taiwan. Preliminary anti-inflammatory screening has shown that the methanolic extracts of solid fermented products of the red alga Mastophora rosea-derived fungal strain Acremonium sp. NTU492 exhibited significant bioactivity. In an attempt to disclose the active principles from this fungal strain, a series of separation and purification was thus undertaken, which has led to the isolation and characterization of seven compounds including four new peptides, namely acrepeptins …

A Rapid Strategy For Screening High-Efficiency Pcsk9 Inhibitors From Ginkgo Biloba Leaves By Ligand Fishing, Hplc-Q-Tof-Ms And Interdisciplinary Assay, Li Li, Meng-Lin Fan, Ya-Nan Li, Ya-Xuan Huang, Xiu-Feng Liu, Ji-Hua Liu

Journal of Food and Drug Analysis

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an attractive target for new cholesterol-lowering drug development. Here, we developed a method integrating ligand fishing, HPLC-Q-TOF-MS and interdisciplinary assay, aiming to explore potential PCSK9 inhibitors from mixtures rapidly and accurately. PCSK9 was expressed and purified firstly, and then the recombined PCSK9 was coated on the surface of magnetic beads (MBs). The PCSK9-immobilized MBs (PCSK9-MBs) were used for ligand fishing combined with HPLC and Q-TOF-MS/MS. Ginkgo biloba leaves (GBL), an herbal medicine widely used in Asia and Europe with good efficacy in treatment of hypercholesterolemia, were chosen as an illustration for ligand fishing. …

Analysis Of Flavor And Other Metabolites In Lemon Juice (Citrus Limon) From Huanglongbing-Affected Trees Grafted On Different Rootstocks, Laura Reuss, Shi Feng, Wei-Lun Hung, Qibin Yu, Frederick G. Gmitter Jr, Yu Wang

Journal of Food and Drug Analysis

Flavor perception integrates sensory input from chemical receptors triggered by taste- and aroma-active metabolites to contribute to food flavor quality. Many factors alter flavor quality. Disease affects aroma and flavonoid constituents, causing off-flavors in plants. Huanglongbing (HLB) disease negatively affects citrus, although lemons are more tolerant. Lemon juice quality of HLB-affected fruits is not well studied. Lemon juice aroma-active compounds were profiled in this study using gas chromatography/mass spectrometry-olfactometry, and other metabolites contributing to overall flavor quality were investigated. Lemon juice from different rootstocks was discriminated using the metabolic profile. Flavor and other lemon juice metabolites also distinguished symptomatic from …

Chemometric Authentication Of Pu'er Teas In Terms Of Multielement Stable Isotope Ratios Analysis By Ea-Irms And Icp-Ms, Honglin Liu, Yitao Zeng, Xin Zhao, Huarong Tong

Journal of Food and Drug Analysis

In this work, the stable isotope ratios of carbon, nitrogen, hydrogen, oxygen, and mineral elements and their stoichiometric methods were examined as possible factors that could certify Chinese tea based on its production years. A total of 43 multi-element stable isotope ratios of Xiangzhujing Pu'er tea in five production years were determined through inductively coupled plasma mass spectrometry (ICP-MS) and elemental analyzer-isotope ratio mass spectrometry (EA-IRMS) methods. Two unsupervised learning techniques (principal component analysis and hierarchical clustering analysis) and three supervised learning techniques (partial least squares discriminant analysis [PLS-DA], back-propagation artificial neural network [BP-ANN], and linear discriminant analysis [LDA]) were …

The Chemical Aspects Of Raman Spectroscopy: Statistical Structure-Spectrum Relationship In The Analyses Of Bioflavonoids, Chih-Hsien Wang, Chia-Chi Huang, Wenlung Chen, Yen-Shi Lai

Journal of Food and Drug Analysis

Raman spectroscopy has been accepted as a useful tool for the characterization of natural products. However, to identify a specific compound in a mixture sample of natural products using Raman spectra alone is highly challenging if not impossible. We demonstrated an effective solution to such issues using a method combining statistical Raman spectroscopy and Mass spectrometry. The method was validated with a successful application to the identification of the major anthocyanin components in a purple yam (Dioscorea purpurea) extract. Of particular interest is that statistical grouping of the bioflavonoid standards that formed the database of this study was found to …

Screening For Malachite Green Contamination On Live Fish Skin With Chewing Gum Based Viscoelastic Sers Sensor, Wan-Li Fan, Shi-Wei Yang, Dong-Mei Wang, Zheng-Jun Gong, Mei-Kun Fan

Journal of Food and Drug Analysis

Malachite green (MG), a prohibited but still found antimicrobial in aquafarm and during live fish shipping, is a hot target in food safety screening. Herein, a novel chewing gum based flexible SERS (G-SERS) sensor was proposed for rapid sampling and detection of MG on live fish skin. The whole analysis takesmin, while the limit of detection for MG is 0.73 pg. Different from other reports, MG contaminated live fish was monitored daily with the G-SERS sensor, during which the fish was firstly raised in 0.5 ppm MG solution for one day, followed by freshwater for a week. It was found …

Uplc-Qtof-Ms Fingerprinting Combined With Chemometrics To Assess The Solvent Extraction Efficiency, Phytochemical Variation, And Antioxidant Activities Of Beta Vulgaris L., Junyi Wang, Guddadarangavvanahally Krishnareddy Jayaprakasha, Bhimanagouda S. Patil

Journal of Food and Drug Analysis

Accurate assays of plant antioxidants and other phytochemicals require efficient extraction conditions and enable rigorous assessments of crop varieties and production systems. This study assessed the extraction of phytochemicals and antioxidants from conventionally or organically grown red and golden beets (Beta vulgaris L.), using twenty solvent (S1eS20) mixtures containing water, methanol, and ethanol alone or with acids (ascorbic, formic, acetic). Red beetroot extracted with methanol with or without acid had the highest betanin content (2791.0 mg/g and 8222.3 mg/g of fresh weight [FW], respectively) and golden beetroot extracted with methanol/ascorbic acid/water had the highest vulgaxanthin I (193.7 mg/g and 15.0 …

Food Preservative Sorbic Acid Deregulates Hepatic Fatty Acid Metabolism, Chia-Hui Chen, Sin-Ni Ho, Po-An Hu, Yu Ru Kou, Tzong-Shyuan Lee

Journal of Food and Drug Analysis

Sorbic acid (SA) is one of the most commonly used food preservatives worldwide. Despite SA having no hepatotoxicity at legal dosages, its effect on hepatic lipid metabolism is still unclear. We investigated the effect of SA on hepatic lipid metabolism and its mechanism of action in C57BL/6 mice. Daily treatment with SA (1 g/kg in diet) for 4 weeks did not alter the body weight, organ weight, and blood lipids in mice. However, hepatic lipid accumulation, particularly that of triglycerides, fatty acids, and glycerol, but not cholesteryl ester and free cholesterol, was increased with SA treatment. Mechanistically, SA decreased the …

The Potential Role Of Phenolic Compounds On Modulating Gut Microbiota In Obesity, Gow-Chin Yen, Hsin-Lin Cheng, Li-Yu Lin, Shiuan-Chih Chen, Chin Lin Hsu

Journal of Food and Drug Analysis

Obesity is a rising public health issue and challenge which is tightly correlated with socio-economic development paralleled with increased energy intake and sedentary behavior that subsequently cause adipose tissue accumulation. Physiological and metabolic status changes during obesity development have been suggested with low grade inflammation of gastrointestinal tract. The gut microbiota plays an essential role in regulating whole body energy metabolism and also lipid accumulation, and immunity of host. However, the detail mechanism of which the gut microbiota composition influence obesity development in humans still need deeper investigation owing to the complex pathophysiology of such disease. Recently, the consumption of …

Transcriptome Studies On The Toxicity Of Silica Nanoparticles, Shih-Yi Hsu

USF Tampa Graduate Theses and Dissertations

Nanotechnology enables more precise harmony in health condition via reducing the dosage amount, improving the delivery of hydrophobic drugs, more specific targeting to the cancerous sites, and so on. Nevertheless, issues regarding the toxicity of nanotechnology have begun to call for attention several decades later after the innovation of nanotechnology. Tools about risk management of nanotechnology have been developed, but recently not much evidence recognizes the toxicity of nanoparticles (NPs) except for some animal studies, which demonstrated organ damage after the exposure to NPs. Toxicogenomic approach refers to the method utilizing gene expression to evaluate the chemical toxicity. Databases as …

Development Of A Pharmaceutical Tablet Authentication System Using Spectroscopic Techniques In Combination With Multivariate Chemometric Methods, Md Nayeem Hossain

Electronic Theses and Dissertations

The spread of falsified drugs is increasing worldwide. Currently, 10%-30% of drugs in the world are falsified. Unfortunately, the supply chain system of developing countries (from manufacturers to customers) is not well monitored and suffers the highest rates of fraudulent activities. Also, the rise of product procurement from the internet increases the chance of American consumers' exposure to poor quality drugs. To combat this horrendous activity, surveillance of pharmaceutical materials is required in the supply chain system. Spectroscopic techniques (e.g., Near-Infrared and Raman spectroscopies) can be a potential solution to authenticate samples in different locations; they are non-destructive, safe, rapid, …

Study Of Pharmaceutical Tablets Using Raman Mapping, Kyle Joseph Pauly

Honors Theses

Covalent bonds are the strongest type of bonds holding molecules together. Based on the pattern of bonding of the molecule, the atoms associated with the bond will vibrate at a specific frequency. Utilizing vibrational spectroscopy, such as Raman spectroscopy, these unique vibrational frequencies can be used to detect the presence of analytes over a selected area. Furthermore, the intensities of the vibrational modes can be tracked to comparatively quantify the concentration of analytes at various locations. This is a method of great importance due to its ability to compare pharmaceutical tablets synthesized with different techniques. Here, the presence and concentration …

Design And Synthesis Of Novel Analogs As Potential Antitubercular Agents, Peggy Mccluggage

Honors Theses

Tuberculosis (TB) is an infectious, airborne disease which primarily infects the lungs. One-third of the world’s population is currently estimated to be infected with Mycobacterium tuberculosis (Mtb), the causative agent for TB [1]. Current treatment for this disease requires at least six months of taking multiple antibiotics with undesirable side effects [2]. Difficulty in complying to this regimen as well as the prevalence of HIV/AIDS has led to antimicrobial resistance seen in Mtb. In order to combat the Multi-Drug Resistant and Extensively-Drug Resistant strains of the disease-causing bacteria, preventative care and novel antibiotics are urgently needed [3]. The purpose for …

Long-Distance Phasing Of A Tentative "Enhancer" Single-Nucleotide Polymorphism With Yp2d6 Star Allele Definitions, Erin C. Boone, Wendy Y. Wang, R Gaedigk, Mariana Cherner, Anick Bérard, J Steven Leeder, Neil A. Miller, Andrea Gaedigk

Manuscripts, Articles, Book Chapters and Other Papers

Background: The CYP2D6 gene locus has been extensively studied over decades, yet a portion of variability in CYP2D6 activity cannot be explained by known sequence variations within the gene, copy number variation, or structural rearrangements. It was proposed that rs5758550, located 116 kb downstream of the CYP2D6 gene locus, increases gene expression and thus contributes to variability in CYP2D6 activity. This finding has, however, not been validated. The purpose of the study was to address a major technological barrier, i.e., experimentally linking rs5758550, also referred to as the "enhancer" single-nucleotide polymorphism (SNP), to CYP2D6 haplotypes >100 kb away. To overcome …

Therapeutic Drug Monitoring Of Apixaban Using Chromogenic Kits, Brooke Vogel

Undergraduate Honors Theses

Apixaban is a novel oral anticoagulant that prevents clotting by directly inhibiting Factor Xa in the coagulation cascade. Due to its different pharmacokinetics, previous standards for testing anticoagulant concentrations are ineffective at measuring apixaban. In this study, Hyphen Biomed Biophen Direct Xa Inhibitor and Biophen Heparin chromogenic kits from Aniara Diagnostica were used along with a NanoDrop™ One/One^C Microvolume UV-Vis Spectrophotometer to see if either of these kits provide acceptable precision and accuracy for the quantification of apixaban in plasma samples, as well as if there is a significant difference in these two kits at varying concentrations of apixaban. …

Antidepressants Versus Music Therapy: Which Treatment Is Better For Treating Depression In Parkinson's Disease?, Emaan Dawood

Virginias Collegiate Honors Council Conference

Music and medicine are merging to treat depression in Parkinson’s disease (PD). Antidepressants, the current standard, demonstrate mixed effects in clinical trials, warranting other treatment options. Here, I compare music therapy to antidepressants in the treatment of depression in PD via literature review. Studies of depressed PD patients undergoing music therapy and/or antidepressants were reviewed with attention to variables including depression (on a patient-reported outcome) that were measured pre- and post- therapy. In the music studies, improvements were seen in depression. Methodological inconsistencies across these studies, a paucity of studies, and small sample sizes, however, necessitate more research to reach …

Orally Administered Nanoscale Drug Delivery System For Colorectal Cancer, Bhavya Shah

USF Tampa Graduate Theses and Dissertations

Mithramycin-A (Mit-A) is a US Food and Drug Administration (FDA) approved chemotherapeutic agent that is used for the treatment of testicular cancer. According to previous studies, Mit-A has shown promising results in targeting colorectal cancer (CRC) and cancer stem cells (CSCs) which are responsible for a highly invasive and metastatic forms of CRC. The use of Mit-A as chemotherapy is limited in CRC due to its toxicity. To minimize its toxicity, we have developed an orally delivered nanoscale drug delivery system by which Mit-A can be delivered using biocompatible and biodegradable materials. Mit-A nanoparticles were prepared using Poly(lactic-co-glycolic acid) as …

Luciferase Reporter Crc Cell Line For Bioluminescence Imaging In Orthotopic Tumor Model, Pratik Chopade

USF Tampa Graduate Theses and Dissertations

CRC is the second most common type of cancer in women and the third most common type of cancer in men. It accounts for 9.7% of all cancers in terms of people diagnosed. Measuring the real-time effect of chemotherapeutic drugs has been a major obstacle in developing a tumor model mouse. Tracking the regression of cancer cells after chemotherapy could be an effective way to resolve this issue. Therefore, cancer cells expressing the constitutive luciferase reporter gene can be a potential solution. The biggest advantage of the luciferase (Luc) reporter is that it is detectable at very low concentrations in …

Identification Of Snps Associated With Multiple Antibiotic Resistance Genes In Eight Clinical Variants Of Enterococcus Faecium., Krishna S. Karia

USF Tampa Graduate Theses and Dissertations

The evolution of multi drug resistant (MDR) bacteria has been well documented these last decade, suggesting that resistance to antibiotics is most commonly associated to single nucleotide polymorphism (SNPs) mutation. To this aim, several molecular methods have been performed to elucidate SNPs in the increasing number of resistant microorganisms. Early detection of MDR bacteria has become of prime necessity in order to combat the disease and ensure public health. Therefore, this research was conducted to screen for SNP mutations correlated to drug resistance in some nosocomial MDR bacteria strains donated from Moffitt Cancer Center (MCC) hospital. Blood, stool, urine, and …

A Micro-Nano Particle System For Sustained Drug Release In Lung Cancer Therapy, Heta N. Jadhav

USF Tampa Graduate Theses and Dissertations

Lung cancer remains the leading cause of cancer-related mortality in men and women worldwide (National Comprehensive Cancer Network). Hence, developing an effective new therapy to treat lung cancer is under intense investigation. Specifically, the sustained release of a drug in lung tumors is critically important. Previous studies at the USF have shown that telmisartan exhibits synergistic properties when combined with Actinomycin-D for lung cancer treatment. The objective of this study is to develop a novel micro/nano system consisting of lipids and chitosan polymers that would be able to deliver Tel directly to the lungs and release its payloads in a …

Sunitinib-Loaded Mpeg-Pcl Micelles For The Treatment Of Age-Related Macular Degeneration, Jarriaun D. Streets

USF Tampa Graduate Theses and Dissertations

Age-related Macular Degeneration, or AMD will be responsible for the vision impairment of more than 5 million late-aged adults in the next 30 years. Current treatment options include frequent intravitreal injections which report high levels of pain resulting in a low patient compliance. However, there are methods of drug delivery that can decrease the amount of intravitreal injections by sustaining drug release. Polymeric micelles, specifically MPEG-PCL have reported superb biocompatibility and more efficient ways of delivering anti-VEGF drugs such as Sunitinib to the posterior segment of the eye. In this study, the novel micellar formulation exhibited an average DLS particle …

Synthesis Of A Targeted Ph Responsive Nanoparticle For Controlled Release Of Actinomycin D, Alejandro Jesus Gonzalez

USF Tampa Graduate Theses and Dissertations

Out of all cancer diagnosis’s, lung cancer has the highest mortality in both sexes making it the leading cause of cancer deaths. Current therapeutic and clinical methods fail to successfully treat the disease, contributed to the development of multi-drug resistance (MDR). Hence, new therapies are needed that can exploit the tumor microenvironment (TME) to target Cancer Stem Cells (CSC). CSCs constitute a key population of the TME, promoting hypoxia, low intracellular pH, and angiogenesis. Actinomycin D (ACD) is a potent CSC inhibitor, but due to its high toxicity and lack of specificity towards cancer cells presents a need for a …

Synthesis Of Fluoroflavonoids As Potential Antioxidant Against Alzheimer’S Disease., Maali Alshammari

Graduate Student Council Research Grants

Overview: Maali Alshammari joined the lab of Professor David A. Colby in spring of 2017; she's currently a third-year Ph.D. student in medicinal chemistry in the graduate program in the Department of BioMolecular Sciences at the University of Mississippi. Maali's project involves the syntheses of fluoroflavones to improve the potency of the antioxidant activity of the original non-fluorinated flavones. The fluoroflavones will potentially be used as neuroprotective agents to prevent the toxic effect of ROS and used to prevent neurogenerative diseases like Alzheimer's.

Intellectual Merit: We are in need of medications that prevent Alzheimer's disease or even reverse its damage; …

The Diffusion Of Artificial Intelligence/Machine Learning Methods And Data Analytics Into An Undergraduate Nursing Research Course, Mary Anne Schultz

Q2S Enhancing Pedagogy

The project is the adoption of principles of Artificial Intelligence (AI)/Machine Learning and Data Analytics into a traditional nursing research (hypothesis testing) course. Necessitated by the recent entrance of “Big Data” use in health care, there is an urgent need to inject an understanding of the AI/ML techniques necessary to extract, organize and derive meaning from this huge amount of evidence in clinical decision-making. In fact, our department recently approved the adoption of Precision Health (PH) (the clinical use of the plethora of highly-individualized data in health & medical decisions) principles into six undergraduate courses, NURS 4222 (Nursing Research & …

Catalytic, Selective, And Stereocontrolled Construction Of C4 Quaternary And Homobenzylic Dihydroisoquinolones By Sp3 C–H Benzylation, Timothy K. Beng, Antonio Moreno

All Faculty Scholarship for the College of the Sciences

C1 benzylated isoquinoline derivatives constitute the core of benzylisoquinoline alkaloids (BIAs). However, their C4 congeners remain elusive. Here, we describe a diastereoselective, catalytic, and modular C(sp³)–C(sp³) coupling protocol wherein β-amino sp³ C–H bonds of readily affordable vicinally functionalized dihydroisoquinolones are replaced by sp³ C–benzyl bonds. The method provides expedient access to C4 quaternary and homobenzylic dihydroisoquinolones, which are attractive fragments for potential drug discovery.

Parp1-Targeted Radiotherapies, Stephen Jannetti

Dissertations, Theses, and Capstone Projects

Poly-ADP-ribosylation reactions were first reported by Chambon in 1963 as enzymatic activity that increases incorporation of ATP in the presence of nicotinamide mononucleotide. In the decades since that publication, Poly(ADP-ribose)polymerase 1 (PARP1) and the PARP family enzymes have been widely studied. PARP enzymes are currently known to play various roles in mammals, including anti-aging processes, interactions with Breast Cancer Suppressor Protein-1 (BRCA1), and DNA damage repair. A significant focus of PARP1 research has been elucidating its role in DNA damage repair. PARP1 is recruited to repair single strand DNA (ssDNA) breaks, which can become double stranded DNA (dsDNA) breaks if …

Neurodevelopment Outcome Of Neonates Treated With Intraventricular Colistin For Ventriculitis Caused By Multiple Drug-Resistant Pathogens-A Case Series, Kashif Hussain, Muhammad Sohail Salat, Gul Ambreen, Javaid Iqbal

Department of Biological & Biomedical Sciences

Background: Multiple-drug-resistant Gram-negative bacteria (MDR-GNB)-associated neonatal ventriculitis is a life-threatening complication that needs timely diagnosis and effective treatment with broad-spectrum antimicrobials in critical-care settings. Inadequate penetration of antibiotics through the blood-brain barrier also demands an intraventricular (IVT) route of administration. This study reports mortality and neurodevelopmental sequelae of neonates till 18 months of age, who received IVT-colistin for treating MDR-GNB associated ventriculitis.
Methods: In a case series of seven neonates with ventriculitis due to MDR-GNB at NICU of Aga Khan University Hospital, Pakistan, between June 2015 and 2018, we reviewed IVT-colistin therapy in critically ill neonates. Treatment outcomes were assessed …

Atomic Force Microscopy (Afm) As A Surface Mapping Tool In Microorganisms Resistant Toward Antimicrobials: A Mini-Review, Zuzanna Grzeszczuk, Antoinette Rosillo, Oisin Owens, Sourav Bhattacharjee

Other resources

The worldwide emergence of antimicrobial resistance (AMR) in pathogenic microorganisms, including bacteria and viruses due to a plethora of reasons, such as genetic mutation and indiscriminate use of antimicrobials, is a major challenge faced by the healthcare sector today. One of the issues at hand is to effectively screen and isolate resistant strains from sensitive ones. Utilizing the distinct nanomechanical properties (e.g., elasticity, intracellular turgor pressure, and Young’s modulus) of microbes can be an intriguing way to achieve this; while atomic force microscopy (AFM), with or without modification of the tips, presents an effective way to investigate such biophysical properties …

Total Cellular Atp Production Changes With Primary Substrate In Mcf7 Breast Cancer Cells., Maggie Louie, Justin Ton, Maurice L. Brady, Diem T. Le, Jordon N. Mar, Chad A Lerner, Akos A Gerencser, Shona A. Mookerjee

Natural Sciences and Mathematics | Faculty Scholarship

Cancer growth is predicted to require substantial rates of substrate catabolism and ATP turnover to drive unrestricted biosynthesis and cell growth. While substrate limitation can dramatically alter cell behavior, the effects of substrate limitation on total cellular ATP production rate is poorly understood. Here, we show that MCF7 breast cancer cells, given different combinations of the common cell culture substrates glucose, glutamine, and pyruvate, display ATP production rates 1.6-fold higher than when cells are limited to each individual substrate. This increase occurred mainly through faster oxidative ATP production, with little to no increase in glycolytic ATP production. In comparison, non-transformed …