Pharmacology Commons^™

Study Proposal For Additional Investigation Of Epac1 In Endothelial Apoptosis, Anh Luu

ONU Student Research Colloquium

Inflammatory states such as sepsis are associated with elevated tumor necrosis factor alpha (TNF-⍺), which facilitates inflammation, increases the production of reactive oxygen species (ROS) and oxidative stress, and contributes to death of endothelial cells (EC). Exchange Factor Directly Activated by cAMP (EPAC1) is an intracellular cyclic-AMP (cAMP) sensor involved in EC responses such as barrier function, angiogenesis and proliferation. Previous studies in our lab demonstrated activation of EPAC1 protected EC from TNF⍺-induced cell death. Specifically, microvascular EC were pretreated for 45 minutes with 100 mM 8-pCPT-2′-O-Me-cAMP (8CPT, specific EPAC1 activator) or 10 mM forskolin (adenylyl cyclase activator that increases …

Antibacterial, Hemagglutination, And Insecticidal Activity Studies On The Solvent Extracts Of The Roots Of Olea Ferruginea, Muhammad Yaseen, Muhammad Kamran, Arshad Farid, Salmah Ismail, Muhammad Muzammal, Kamal Abdul Amir, Muhammad Hashim Khan, Sohail Ahmad, Sheikh Abdur Rashid

Makara Journal of Science

Olea ferruginea has been used to treat skin ailments, as well as kidney and ocular problems for a long time. The current study was designed with the aim of investigating and scientifically validating its widespread use. Chloroform, n-hexane, and ethyl acetate were used to assess the antibacterial, hemagglutination, and insecticidal properties of O. ferruginea roots. Escherichia coli, Micrococcus luteus, Klebsiella pneumoniae, and Pseudomonas aeruginosa were among the bacterial strains selected for assessing antibacterial activity. The results showed that ethyl-acetate (EtOAc) extract (56%) and chloroform (CHCl₃) extract (56%) showed the widest zone of inhibition against …

Efforts To Increase The Ketamine-Like Activity Of The Rapid-Acting Antidepressant Ro-25-6981 (Mi-4) By Increasing Ampa Potentiation, Nathan Heger

Annual Research Symposium

The small molecule ketamine has generated much interest due to its rapid antidepressant effects. Despite having a rapid onset, ketamine has poor bioavailability, short duration of action, toxicities with long-term use, and a high potential for abuse. The molecule MI-4 (RO 25-6981) has also been shown to have both a rapid and sustained antidepressant effect. Most of the research into the mechanism of the rapid onset of MI-4 and ketamine has focused on their interaction with the NMDA receptor in addition to some monoamine transporters. Some recent publications have shown a significant role of AMPA receptors in the ketamine antidepressant …

The Use Of Atmospheric-Pressure Chemical Ionization For Pesticide Analysis Using Liquid Chromatography Mass Spectrometry, Pei-Ting Jiang, Kuan-Lu Wu, Hsueh-Ting Wang, Sung-Fang Chen

Journal of Food and Drug Analysis

Based on the regulations of the Ministry of Health and Welfare (MOHW) of Taiwan in 2017, an analysis of 373 pesticides in food was conducted using the MOHW official method. The analyses involved the use of either liquid chromatography mass spectrometry (LC-MS) with electrospray ionization (ESI) or gas chromatography mass spectrometry (GC-MS) with electron ionization (EI). In this study, the applicability of detecting pesticides using atmospheric pressure chemical ionization (APCI) was investigated and evaluated. The pesticides were separated using an aqueous solution of ammonium formate with methanol as the mobile phase, and ionization efficiency was compared between APCI, ESI, and …

A Substructure-Based Screening Approach To Uncover N-Nitrosamines In Drug Substances, Yu-Ting Kao, Shu-Fen Wang, Meng-Hsiu Wu, Shwu-Huey Her, Yi-Hsuan Yang, Chung-Hsien Lee, Hsiao-Feng Lee, An-Rong Lee, Li-Chien Chang, Li-Heng Pao

Journal of Food and Drug Analysis

Drug substances are at risk of contamination with N-nitrosamines (NAs), well-known carcinogenic agents, during synthesis processes and/or long-term storage. Therefore, in this study, we developed an efficient data-based screening approach to systemically assess marketed products and investigated its scalability for benefiting both regulatory agencies and pharmaceutical industries. A substructure-based screening method employing DataWarrior, an open-source software, was established to evaluate the risks of NA impurities in drug substances. Eight NA substructures containing susceptible amino sources for N-nitrosation have been identified as screening targets: dimethylamine (DMA), diethylamine, isopropylethylamine, diisopropylamine, N-methyl-2-pyrrolidone, dibutylamine, methylphenylamine, and tetrazoles. Our method detected 192 drug …

Repurposing Lansoprazole And Posaconazole To Treat Leishmaniasis: Integration Of In Vitro Testing, Pharmacological Corroboration, And Mechanisms Of Action, Yash Gupta, Steven Goicoechea, Jesus G. Romero, Raman Mathur, Thomas R. Caulfield, Daniel P. Becker, Ravi Durvasula, Prakasha Kempaiah

Journal of Food and Drug Analysis

Leishmaniasis remains a serious public health problem in many tropical regions of the world. Among neglected tropical diseases, the mortality rate of leishmaniasis is second only to malaria. All currently approved therapeutics have toxic side effects and face rapidly increasing resistance. To identify existing drugs with antileishmanial activity and predict the mechanism of action, we designed a drug-discovery pipeline utilizing both in-silico and in-vitro methods. First, we screened compounds from the Selleckchem Bio-Active Compound Library containing ~1,622 FDA-approved drugs and narrowed these down to 96 candidates based on data mining for possible anti-parasitic properties. Next, we completed preliminary in-vitro testing …

Effect Of Repeated Shengmai-San Administration On Nifedipine Pharmacokinetics And The Risk/Benefit Under Co-Treatment, Hong-Jaan Wang, Elise Chia-Hui Tan, Tzu-Yi Chiang, Wei-Ching Chen, Chien-Chang Shen, Yune-Fang Ueng

Journal of Food and Drug Analysis

Herbal interactions with nifedipine/felodipine through cytochrome P450 (CYP) 3A inhibition is significant in humans. Shengmai-San (SMS), a three-herbal formula of Chinese medicine, is commonly prescribed in Asia populations for cardiovascular disorders. This study aimed to elucidate the impact of SMS on nifedipine/felodipine treatment by the findings from rat pharmacokinetic study of nifedipine to the retrospective cohort study of patients with hypertension. The 3-week SMS treatment increased the systemic exposure to nifedipine by nearly two-fold and decreased nifedipine clearance by 39% in rats. Among the ingredients of SMS component herbs, schisandrin B, schisantherin A, and methylophiopogonanone A, inhibited the nifedipine oxidation …

Evaluation Of Opioid Consumption Trends For Pain In Taiwan And Comparison With Neighboring Asian Countries, Jhi-Joung Wang, Shu-Fang Teng, Yu-Roo Chu, Chin-Chen Chu, Chung-Han Ho, Li-Ling Chu

Journal of Food and Drug Analysis

Opioids are effective analgesics for pain relief, however, inappropriate use may cause risks. The aims of the study were to evaluate trends of opioid consumption for pain management in Taiwan and compare them among neighboring Asian countries. Opioid consumption data, including fentanyl, morphine, oxycodone, hydromorphone, codeine, and pethidine, were collected from the Controlled Drugs Management Information System of Taiwan Food and Drug Administration from 2008 to 2018. Data of different continents and neighboring Asian countries were retrieved from the WHO website. The major findings include: (1) In Taiwan, the total annual opioid consumption has gradually increased from 2008 to 2018, …

A Three-Step Stacking Capillary Electrophoresis Of Field-Amplified Sample Injection, Sweeping, And Micellar Collapse For Determination Of Dabigatran And Its Active Metabolite In Human Plasma, Cheng-Wei Cheng, Wen-Han Feng, Wei-Hua Tang, Hwang-Shang Kou, Chun-Chi Wang, Shou-Mei Wu

Journal of Food and Drug Analysis

A three-step stacking capillary electrophoresis (CE) composed of field-amplified sample injection, sweeping, and analyte focusing by micellar collapse (FASI-sweeping-AFMC) was developed to determine dabigatran (D) and its major active metabolite, dabigatran acyl-beta-d-glucuronide (DAG), in human plasma. After optimization and validation, this novel approach was further applied to monitor 5 real samples, and the 25.2 to 186.8 ng mL^-1 D could be observed among those. Based on these results, the novel CE stacking strategy was successfully applied for the analysis of D and DAG in human plasma and could be served as a tool for clinical assays.

The Antihyperlipidemic Equivalent Combinatorial Components From Peel Of Citrus Reticulata ‘Chachi’, Ping-Ting Xiao, Yu-Jia Kuang, Shi-Yu Liu, Zhi-Shen Xie, Jin-Hua Hao, E-Hu Liu

Journal of Food and Drug Analysis

Since the combinatorial components responsible for the antihyperlipidemic activity of Citrus reticulata‘Chachi’ (CRC) peels remains unclear, we herein developed a bioactive equivalence oriented feedback screening method to discover the bioactive equivalent combinatorial components (BECCs) from CRC peels. Using palmitic acid (PA)- stimulated hepatocyte model, a combination of five polymethoxyflavones (PMFs) including tangeretin, sinensetin, nobiletin, 5,7,8,4′-tetramethoxyflavone and 3,5,6,7,8,3',4'-heptamethoxyflavone was identified to be responsible for the antihyperlipidemic effect of CRC peels. Via evaluation of combination effect by combination index (CI), these 5 PMFs were found to take effect via a synergistic mode. Our data indicated that the antihyperlipidemic mechanism of PMF …

Food Glycomics: Dealing With Unexpected Degradation Of Oligosaccharides During Sample Preparation And Analysis, Yu-Ping Huang, Randall C. Robinson, Daniela Barile

Journal of Food and Drug Analysis

This study reveals that unexpected degradation of food oligosaccharides can occur during conventional glycomics workflows, including sample preparation and analysis by liquid chromatography-mass spectrometry (LC-MS). With the present investigation, we aim to alert the scientific community of the susceptibility of specific glycosidic linkages to degradation induced by heat and acid. Key standard oligosaccharides representing the major types found in foods (3’-sialyllactose and 6’-sialyl-N-acetyllactosamine for milk, raffinose and stachyose for legumes) were selected as model systems and underwent each of the following treatments independently: (1) labeled with the derivatizing agent 1-aminopyrene-3,6,8-trisulfonic (APTS) (followed by analysis with a capillary electrophoresis system coupled …

Ulva Prolifera Polysaccharide Exerts Anti-Obesity Effects Via Upregulation Of Adiponectin Expression And Gut Microbiota Modulation In High-Fat Diet-Fed C57bl/6 Mice, Hai-Ching Pung, Wei-Sheng Lin, Yi-Chen Lo, Cheng-Chih Hsu, Chi-Tang Ho, Min-Hsiung Pan

Journal of Food and Drug Analysis

Obesity is characterized by metabolic disorder and accompanying an altered and less diverse gut microbiota composition during a fat-enriched diet. Recent studies indicated that sulphated polysaccharide prevents high-fat diet (HFD) induced obesity, reduces metabolic disorder, and restores the gut microbiota. However, there are few studies about Ulva prolifera polysaccharide (UPP) may induce anti-obesogenic effects. Therefore, the present study investigates the enzymatic extracted UPP effects in HFD-fed mice. The results showed that UPP considerably slowed down the HFD-induced weight gain and improved metabolic disorders in HFD-fed mice. Notably, the effects were associated with lower body weight gain, reduced adipose tissue hypertrophy, …

Stable Carbon Isotopic Characterization Of Rice Vinegar Protein As An Intrinsic Reference For Discriminating The Authenticity Of Brewed Rice Vinegar, Chun-Jen Fang, Hsin-Cheng You, Zih-Ling Huang, Che-Lun Hsu, Chia-Fen Tsai, Ya-Tze Lin, Ya-Min Kao, Su-Hsiang Tseng, Der-Yuan Wang, Nan-Wei Su

Journal of Food and Drug Analysis

Rice vinegar plays an important role in daily life. However, some unscrupulous manufacturers may deliberately add synthetic acetic acid in vinegar products to reduce fermentation time and save production costs. To protect the rights and health of consumers, vinegar authenticity must be controlled. The rice vinegar protein was used as an intrinsic reference and its stable carbon isotope ratio (δ¹³C_protein) was analyzed by elemental analyzer-isotope ratio mass spectrometry. The stable carbon isotope ratio difference between the acetic acid and the rice vinegar protein (Δδ¹³C_{acetic acid-protein}) was calculated to evaluate vinegar authenticity. Sixteen …

Direct Immersion Solid-Phase Microextraction Combined With Ambient Ionization Tandem Mass Spectrometry To Rapidly Distinguish Pesticides In Serum For Emergency Diagnostics, Hung Su, Hsin-Hua Lin, Lin-Jhen Su, Chia-Chen Lin, Zong-Han Jiang, Shiang-Jin Chen, Jentaie Shiea, Chi-Wei Lee

Journal of Food and Drug Analysis

Despite the fact that carbamates and organophosphates cause acute poisoning via different mechanisms and require disparate management, they are indistinguishable by current clinical assays. Herein, direct immersion solid-phase microextraction (DI-SPME) plus thermal desorption-electrospray ionization tandem mass spectrometry (TD-ESI/MS/MS) was developed to discern them. Both pesticides spiked in human serum were extracted by SPME and analyzed by TD-ESI/MS/MS. This is a promising emergency care platform as rapid analyses could be done in tiny sample volumes with satisfactory recovery (89.46%–116.32%), precision (covariance < 20%), sensitivity (LOD < 0.1 µg/mL), turnaround time (< 5 minutes), and linearity (R² = 0.9827–0.9992) within 0.1–100 µg/mL.

Determination Of Perfluoroalkyl Substances In Food Packaging In Taiwan Using Ultrasonic Extraction And Ultra-Performance Liquid Chromatography/Tandem Mass Spectrometry, Peng Siao, Su-Hsiang Tseng, Chia-Yang Chen

Journal of Food and Drug Analysis

Perfluoroalkyl substances (PFASs), as coating materials, possess oil-resistant and waterproof properties. However, their persistency and toxicity have caused concerns. This study developed a method for determining five types of 20 PFASs with ultra-performance liquid chromatography/tandem mass spectrometry, and measured seven categories of 32 commercial samples of oil-resistant food packaging in Taiwan. The assay was validated according to the specification of Taiwan Food and Drug Administration (TFDA). Samples of 100 cm² were cut into pieces and were ultra-sonicated in 20-mL methanol at 50℃ for 45 minutes. The extracts were concentrated to 1 mL for instrumental analysis. Most matrix effect factors …

The Next Generation Beneficial Actions Of Novel Probiotics As Potential Therapeutic Targets And Prediction Tool For Metabolic Diseases, Hsin-Lin Cheng, Gow-Chin Yen, Shih-Chien Huang, Shiuan-Chih Chen, Chin-Lin Hsu

Journal of Food and Drug Analysis

The prevalence of metabolic disease has rising and affected over 1,000 million populations globally. Since the metabolic disease and its related complication are board, it has become the major health hazard of modern world. However, Long term medication of metabolic disease may cause serious side effects and risk for adverse health problems. Recently, emerging studies focus on exploring the mechanistic details of metabolic state in disease development and progression. Gut bacteria ecosystem was considered to play a pivotal role in regulating energy homeostasis and great associated with the development of metabolic disease. Accumulated evidences indicated that Akkermansia muciniphila, Faecalibacterium prausnitzii, …

Enhancing The Capabilities Of Fluid Bed Granulation Through Process Automation And Digitalisation, Marcus O'Mahony, Caroline Mccormack, Chris O'Callaghan, Ian Jones, Gavin Walker, Patrick Cronin

Level 3

This paper describes a PAT-enabled, digitalised, and automated fluid bed granulation system. A multichannel Near-Infrared (NIR) spectrophotometer and a direct imaging particle size and shape analyser in constant dialogue with the SmartX no-code/low-code platform provide a ground-breaking process automation toolset now located at the Bernal Institute in the University of Limerick. Two sets of results are presented for this study, from two iterations of the Advance Dynamic Process Control (ADPC) controller application. The results demonstrate the direct measurement and control of the product’s critical quality attributes through digitality enabled feedback control of processing setpoints and parameters. The platform controlled the …

Effect Of Rehmannia Glutinosa Libosch Extract On Proliferation And Cardiogenic Pre-Differentiation Of Human Mesenchymal Stem Cells, Huu Dat Nguyen, Len Ho Thi, Xuan Bach Ho, Van Anh Cao, Duy Minh Le Hoang

BioMedicine

Background: Vietnamese medicine tried and tested certain bioactive compounds from plants to increase the rate of tissue immunomodulation, regeneration, and differentiation. Although there are many research papers discovered about phytochemicals of Rehmannia glutinosa Libosch and differentiation induction potential of some substances purified from this herbal, it finds difficult to seek research that investigated the effect of Rehmannia glutinosa Libosch extract on proliferation and cardiogenic differentiation of mesenchymal stem cells, even though it has commonly been used for a long time because of its function as a restorative and as a critical role in cardiovascular treatment in traditional.

Results: Our …

Exploring Pathways From Data To Knowledge To Insights In The Pharmaceutical Industry: ‘Introducing The Pharmaceutical Knowledge Ecosystem’, Melanie J. Adams, Paige E. Kane, Anne Greene (Editor), Martin Lipa

Level 3

The ecosystem of how the pharmaceutical industry acquires data, transforms these data into tangible knowledge, and derives valuable insights throughout the process, is highly complex. Data, information, knowledge, and the resulting insights, are necessary to support decision- making, manage risk, problem solve, ensure product realisation, enable continual improvement, and enhance operational effectiveness. Building on the fundamental concepts established in the well-known Data Information Knowledge Wisdom (DIKW) hierarchy, this paper reviews the basic concepts involved in the DIKW pathway and begins to relate these concepts to both established capabilities (e.g., PAT), existing requirements (e.g., data integrity), and emerging trends in the …

Improving Risk-Based Decision Making (Rbdm) Effectiveness Through A Framework Which Integrates Knowledge And Risk, Martin Lipa, Valerie Mulholland, Anne Greene (Editor)

Level 3

This paper explores the emergence of the importance of knowledge in Risk-Based Decision Making (RBDM) and Quality Risk Management (QRM) through a detailed review of ICH Q9(R1) (Step 2) and presents a framework(the RKI cycle) to integrate knowledge and risk and associated six principles to operationalise it.