Pharmacology, Toxicology and Environmental Health Commons^™

Therapeutic Dual-Targeting Of Cytosolic And Mitochondrial One-Carbon Metabolism, Aamod Sanjeev Dekhne

Wayne State University Dissertations

One-carbon metabolism (1CM) is compartmentalized in the mitochondria and cytosol and generates a host of metabolites critical to tumor propagation. Although drug-targeting of cytosolic 1CM remains a clinically-relevant mainstay, development of clinically-useful agents targeting mitochondrial 1CM remains elusive. Of particular pharmacological interest is the mitochondrial 1CM enzyme, serine hydroxymethyltransferase2 (SHMT2). SHMT2 expression correlates with the oncogenic phenotype in lung, colon, breast, glioma, and liver cancer and, overall, is the fifth-most differentially expressed metabolic enzyme in cancer cell versus normal tissue. Despite the unequivocal oncogenic importance and therapeutic potential of SHMT2, there are no clinically relevant (i.e. active in vivo) inhibitors …

Development And Characterization Of An Adaptable Aerosolized Methylene Diphenyl Diisocyanate Generation System, Simon Aubin, Loïc Wingert, Sébastien Gagné, Livain Breau, Jacques Lesage

Études primaires

Reactive semivolatile contaminants, such as isocyanates, can be particularly difficult to assess in occupational environments. While standard methods exist for isocyanates, there are still significant differences between the results they provide for various occupational environments or processes. This study presents the validation of a laboratory system for the generation of controlled atmospheres of isocyanates. A system consisting of different modules generated airborne methylene diphenyl diisocyanate (MDI) by nebulizing a solution into mixing and exposure chambers with control of flow rate, temperature, and relative humidity. Sampling was performed through an eight-port flow splitter that allowed only very slight within-test variability. MDI …

Occupational Exposure To Antineoplastic Drugs: What About Hospital Sanitation Personnel?, France Labrèche, Capucine Ouellet, Brigitte Roberge, Nicolas J Caron, Ahmed Yennek, Jean-François Bussières

Études primaires

Objective

Occupational exposure to antineoplastic drugs (ANPs) occurs mainly through dermal contact. Our study was set up to assess the potential exposure of hospital sanitation (HS) personnel, for whom almost no data are available, through contamination of surfaces they regularly touch.

Methods

In the oncology departments of two hospitals around Montreal, surface wipe samples of 120–2000 cm² were taken at 10 sites cleaned by the HS personnel and five other sites frequently touched by nursing and pharmacy personnel. A few hand wipe samples were collected to explore skin contamination. Wipes were analyzed by ultra-performance liquid chromatography tandem–mass spectrometry for …

The Protective Effects Of Mir-210 Modified Endothelial Progenitor Cells Released Exosomes In Hypoxia/Reoxygenation Injured Neurons, Sri Meghana Yerrapragada

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Endothelial progenitor cells (EPCs) have been shown to provide beneficial effects on oxidative stress. Exosomes (EXs) released from these stem cells could be one of the major contributors, as they are known to convey the benefit of one cell to another cell via microRNAs (miRNA). At first, we determined that EPCs release more EXs when they are serum-starved for 48 hours., and by determining the microRNA-210 (miR-210) levels in the EXs, we found that miRNA is being transferred from cells to EXs. Meanwhile, miR-210 is gaining popularity in reducing elevated oxidative stress levels. In this study, we investigated the role …

The Effect Of Circadian Clock Modulation On Cisplatin Cytotoxicity, Nadeen Nibal Ahmad Anabtawi

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Cisplatin is a DNA damage-based chemotherapeutic drug widely used to treat various types of cancers; however, the treatment's toxicity restricts its efficiency. Studies have shown that the circadian rhythm controls the DNA damage response and affects the repair pathways of cisplatin-induced DNA damage. Circadian clock modulation, therefore, has been proposed to be a potential mechanism for enhancing cisplatin tolerability. Here we used clock-enhancing molecules to evaluate the effect of pharmacological clock modulation on cisplatin cytotoxicity. Using cultured human cell lines, cisplatin cytotoxicity was found to be attenuated following treatment with circadian-enhancing molecules KS15 and SR8278. Moreover, the protein and mRNA …

Functions Of Atr Kinase In Terminally Differentiated Human Epidermal Keratinocyles And In Human Ex-Vivo Skin After Exposure To Ultraviolet B Radiation, Vivek Shashank Nag Gogusetti

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The functions of Ataxia telangiectasia and Rad-3 related protein (ATR) is very much important in a cell, as it is a DNA damage response protein, which plays an important role in cell division, DNA repair and apoptosis. This protein helps in proliferation in the actively DNA dividing normal cells and in cancer cells. The functions of ATR in a proliferating cell are well studied and known to involve regulation of replication fork and cell cycle progression after DNA damage. Whereas, in a non-replicating cell, the functions of ATR are not so well known. In the human body, most of the …

Xeroderma Pigmentosum A Deficiency Results In Increased Generation Of Microvesicle Particles In Response To Ultraviolet B Radiation, Christian Lea Rajeshkumar

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Xeroderma Pigmentosum is a genetic disorder in which ability to repair DNA damage such as from UV radiation is decreased. Nucleotide excision repair is known for repairing DNA damage caused by UV radiation and XPA plays a major role in recognizing and eliminating abnormal section of DNA. Therefore, XPA deficiency decreases repair efficiency of DNA. Of note, XPA deficiency is linked with photosensitivity. Microvesicle particles are membrane-bound particles which are released into the extracellular environment in response to multiple stimuli including the lipid Platelet activating factor (PAF). Previous studies have shown that XPA deficiency can induce increase production of reactive …

Stress-Induced Senescence In Human Dermal Fibroblasts : Effects Of Creatine And Nicotinamide Post Stress Treatment, Venkata Sravya Arikatla

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In skin connective tissue, dermal fibroblasts appear to be the most prevalent cell type. They are in charge of making the extracellular matrix that makes up the skin's connective tissue, and also involved in wound healing. Moreover, they produce Insulin-like growth factor-1 (IGF-1) which helps in activation of Insulin growth factor-1 receptor (IGF-1R). This receptor helps to control cell proliferation and responses to DNA-damaging substances such as UVB radiation, reactive oxygen species (ROS), and therapeutic drugs. According to our findings, lack of IGF-1 expression in the dermis of elderly patients due to fibroblast senescence (senescence is characterized by which cells …

Survival, Growth, And Characterization Of Microbes In E-Liquids, Jessica Bunn

Master of Science in Forensic Science Directed Research Projects

Health risks associated with the use of e-cigarettes have become a concern in the last ten years, including the inhalation of volatile organic compounds, trace heavy metals, and cancer-causing agents. An additional, but poorly characterized health threat for e-liquids is the potential for bacterial contamination since the presence of pathogenic organisms can potentially cause disease from the inhalation of the microbes into the lungs. This work aims to investigate microbial growth and survival within the e-liquid matrix. Bacillus cereus T. strain and Escherichia coli were the chosen organisms for analysis of growth by absorbance, survival by viable plate counts, and …

Analysis Of Ethanol Aerosolized In An Electronic Cigarette By Headspace Gas Chromatography-Flame Ionization Detector (Gc-Fid) And Particle Size Separation, Erica R. Sales

Master of Science in Forensic Science Directed Research Projects

Electronic cigarettes (e-cigs) were designed as a healthier alternative nicotine delivery system, and involve the heating of e-liquids. These are composed of propylene glycol, vegetable glycerin, flavoring agents, and nicotine. Recently, ethanol has been identified as an unlabeled ingredient. The health consequences are currently unknown.

The purpose of this study is to quantify the amount of ethanol present in an aerosol cloud and to determine the size of the ethanol particles. A SubOx Mini-C e-cig was used. For ethanol quantification, the e-cig was attached to a Buchner Flask containing 150mL of deionized water, The system was attached to a vacuum …

Long Term Nutrient And Chlorophyll A Dynamics Across Long Island Sound And Impacts On Dissolved Oxygen Conditions Within The Western Sound (1991-2019), Sherry Perreira

Dissertations and Theses

Nitrogen overload, eutrophication, and hypoxia have been challenging and persistent water quality problems in Long Island Sound (LIS) over the past decades with major impacts on commercial industries, ecology, and recreational activities in the region. Recognizing these problems, the EPA enforced three phases of the Clean Water Act (CWA) to reduce nitrogen loads in an effort to improve this important estuary. This study examines how nitrogen (NH₃, NO_x & TDN), chlorophyll a (CHLA), and dissolved oxygen (DO) concentrations changed in LIS over the past 30 years, in response to water quality regulations as well as changes in …

Synthesis, Molecular Docking, And Biological Evaluation Of Novel 2-(3-Chlorophenyl) Quinoline-4-Carboxamide Derivatives As Potent Anti-Breast Cancer And Antibacterial Agents, Kailas W. Shinde, Prashant S. Kharkar, Chetan P. Shah, Shrimant V. Rathod

The Thai Journal of Pharmaceutical Sciences

Objectives: The study aims to synthesize and to evaluate the anti-breast cancer and antibacterial activity of some novel quinoline-4-carboxamide derivatives. Materials and Methods: A series of novel quinoline analogs 6a-6j with varied substituent (X = H, F, OCH3, NO2) were synthesized from aniline through multi-step reactions in good yields. All analogues were confirmed by spectral characterization, namely, FT-IR, MS, 1H-NMR, and 13C-NMR. All the molecules were evaluated for their anticancer activity against a breast cancer cell line, MDA-MB-231 by MTT assay, and antibacterial activity against Gram-positive bacteria (Staphylococcus aureus 6538p and Bacillus subtilis) and Gram-negative bacteria (Escherichia coli and Pseudomonas …

Doxorubicin Modulates P-Glycoprotein Transcription Differently During Caco-2 Differentiation, Udomsak Udomnilobol, Suree Jianmongko

The Thai Journal of Pharmaceutical Sciences

P-glycoprotein (P-gp) is an efflux transporter protecting cells from various chemical threats. Upregulation of P-gp expression, mediated by reactive oxygen species (ROS), has been reported in doxorubicin-treated cells. However, during cell differentiation cellular redox status may vary. This study investigated the influence of cell differentiation on doxorubicin-mediated P-gp expression in Caco-2 cells, and its relation to cellular redox status. During 21-day culture, Caco-2 cells were divided into pre-, during-, and post-differentiation, based on total cell numbers, percentage of G0/G1 cells, and alkaline phosphatase activity. Our study demonstrated that Caco-2 cells were in a more reduced state on differentiation. At low …

Evaluation Of Acute Oral Toxicity Of Methanolic Fractions Of Sesbania Grandiflora Linn. Roots In Albino Mice, N. S. Vinay, S. Babitha, R. Nandeesh, S. Paramesh, E. Manjunath, J. P. Geetha, V. P. Veerapur, B. Swetha, H. V. Keerthi Prasanth

The Thai Journal of Pharmaceutical Sciences

Introduction: Although Sesbania grandiflora Linn. roots have valuable pharmacological effects, the comprehensive awareness about its toxicity potential has been lacking. Objectives: The objectives of the study were to assess the acute oral toxicity of methanolic fraction of S. grandiflora root (MFSGR). Materials and Methods: The female albino mice were divided into two groups (n = 5), one group served as normal control while the other treated with MFSGR (2000 mg/kg, p.o). Both the groups of mice were observed for 14 days for various parameters according to the Organization for Economic Cooperative and Development guidelines 425 TG. Results: Oral administration of …

Pharmacognostic And Chromatographic Evaluation Of Male And Female Flowers Of Coscinium Fenestratum For Berberine Content And Its Effect On Antioxidant Activity, T. S. Roopashree, Kuntal Das, N. Prashanth, K. Rakesh Kumar

The Thai Journal of Pharmaceutical Sciences

Coscinium fenestratum (CF) (Gaertn.) Colebr., [Family: Menispermaceae] is an endangered species of dioecious liana found in Western Ghats of India. The present investigation aimed with systematic analytical studies on the macroscopic, microscopic examination of male and female CF flowers, various solvent extractions, accompanied by phytochemical screening through chemical tests, identification of Berberine alkaloids, antioxidant activity, and Berberine quantification byhigh-performance thin-layer chromatography (HPTLC) process. Two different amounts of solvents (10 ml and 20 ml) with two different time intervals, that is, 15 min and 25 min, respectively, were used for extraction. Results revealed that both flowers had their own unique characters. …

Anthraquinones Extracted From Rubia Cordifolia Linn As Potential Ligands To Treat Alzheimer’S Disease, Pottella Srinivasulu, Janga Ramesh Babu, T.N.V. Ganesh Kumar, Padarthi Pavan Kumar, S. Vidyadhara

The Thai Journal of Pharmaceutical Sciences

Objective: The present investigation aims to predict the pharmacokinetic aspects and assessing the anti-Alzheimer’s activity using both molecular docking platform and ex vivo pharmacological studies on muscle contraction. Materials and Methods: 2-Methyl Anthraquinone (MAQ) and Quinizarine (QNZ) were isolated from Rubia cordifolia L., and evaluated for absorption, distribution, metabolism, excretion, and toxicity. Molecular docking was performed with the help of Mcule software on five drug targets acetylcholinesterase enzyme (AChE), cyclin-dependent kinase5 (CDK5), glycogen synthase kinase 3β (GSK3β), monoamine oxidase (MAO-B), and β-secretase enzyme (BACE). The pharmacological activity was screened by recording the muscle contractions of chick ileum. Results: The selected …

Current Perspectives On The Therapeutic Potential Of Mitragyna Speciosa And Its Derivatives On Animal Model, Norsyifa Harun, Illa Syafiqah Johari, Rima Atria Japarin, Farah Wahida Suhaimi, Zurina Hassan, Mohammed Shoaib

The Thai Journal of Pharmaceutical Sciences

The plant Mitragyna speciosa Korth. is receiving increased attention as a therapeutic substitution for opioid use disorder (OUD). The active alkaloids constituents of the plant, particularly mitragynine and 7-hydroxymitragynine, have been shown to modulate opioid receptors, acting as agonists at mu-opioid receptors. Given this pharmacology, several studies have examined the abuse and dependence potential of M. speciosa and its alkaloids in various animal models of dependence. In addition to action on opioid receptors, the Mitragyna alkaloids also appear to exert diverse activities at other receptors in the central nervous system which may explain the complex pharmacological profile of these alkaloids. …

Evidence For Intravenous Self-Administration Of Mitragynine In Fentanyl-Dependent Rats, Norsyifa Harun, Zurina Hassan, Surash Ramanathan, Mohammed Shoaib

The Thai Journal of Pharmaceutical Sciences

Introduction: Kratom (Mitragyna speciosa Korth) is currently used as an alternative for the self-treatment of pain and management of opioid dependence and withdrawal. Due to the opioid-like effect of the plant’s active alkaloid, mitragynine (MG), the evaluation of its ability to maintain self-administration in animal models of opioid dependence appears to be great significance. Objectives: Here, the ability of MG to cross-substitute to the reinforcing effects of the synthetic narcotic fentanyl is investigated. Methods: Rats with implanted catheters were allowed to self-administer fentanyl (2.0 μg/kg/infusion) on a fixed-ratio 1 of schedule of reinforcement. Results: A significant increase in lever pressing …

Synthesis And Anti-Inflammatory Effects Evaluation Of 1,3 Substituted Isatin Derivatives, Farshid Hassanzadeh, Elham Jafari, Nahal Khayambashi, Valiollah Hajhashemi

The Thai Journal of Pharmaceutical Sciences

Objectives: Inflammation is a pathophysiological response of the body to a variety of agents including infections and physical injury leading to local accumulation of plasma fluid and blood cells. Isatin as a promising heterocyclic molecule has shown interesting biological profile. In this study, some derivatives of isatin containing both Schiff and mannich base fragments were synthesized in a three-step procedure. Methods: Benzohydrazide derivatives were prepared by reaction of benzoat derivatives with hydrazine hydrate. The Schiff bases were formed by treatment isatin with the benzo hydrazide derivatives. The corresponding mannich bases have been synthesized by the reaction of the Schiff bases …

Present Clinical Trial Regulatory System And Strategies For Improvement In Thailand, Charunee Krisanaphan, Rungpetch Sakulbumrungsil

The Thai Journal of Pharmaceutical Sciences

The study aimed to identify gaps and to develop strategies for improving the clinical trial regulatory system in Thailand. Two-step cross-sectional survey was conducted. The first questionnaire addressed the present situation and the expected system sent by mail. The participants were from the lists of ethics committee (EC) members available online and others obtained from Food and Drug Administration (FDA). The second questionnaire determined the strategies and methods to improve the regulatory system. The participants were the attendees at the Thailand Toward Excellence in Clinical Trials meeting. The first questionnaire with response rate of 26.9% showed that the present situation …