Pharmacology, Toxicology and Environmental Health Commons^™

In Vitro Antioxidants And Anticancer Activity Of Crude Extract Isolates From Euphorbiaceae In Northern Thailand, Siwalee Rattanapunya, Wiriyaporn Sumsakul, Akharasit Bunsongthae, Samart Jaitia

The Thai Journal of Pharmaceutical Sciences

The properties of Croton persimilis Müll.Arg. and Antidesma puncticulatum Miq.— interesting plant in the family Euphorbiaceae were investigated. The ethanol crude plant extracts were established for phytochemicals screening, antioxidants activities, anticancer in five important human cancer cell lines (MCF-7, MDA-MB-231, HeLa, HepG2, and NCI-H187), and cytotoxic activity in normal cell line (hTERT-HME1). The leaves extracts of C. persimilis Müll. Arg. contained flavonoids, saponins, terpenoids, and tannins. The total phenolic content properties were found in 43.40 ± 1.36 mg Gallic Acid Equivalents (GAE)/g crude extract. They also showed lowest antioxidant activity through 2, 2-diphenyl-1-picrylhydrazyl (DPPH) assay (IC50>1,000 μg/ml) and 2.4.2 …

Incidence Of Pneumocystis Carinii Pneumonia In Treatment-Naïve Hiv-Infected Adult Patients Receiving Primary Pneumocystis Carinii Pneumonia Chemoprophylaxis With 48-Week Antiretroviral Initiation, Piroon Khamlee, Peerawong Werarak, Chankit Puttilerpong

The Thai Journal of Pharmaceutical Sciences

Objective: The objective of the study was to determine the incidence of primary Pneumocystis carinii pneumonia (PCP) between patients who received and did not receive primary PCP chemoprophylaxis and investigate adverse drug reactions (ADRs) related to the chemoprophylaxis use. Method: A retrospective study was conducted in Siriraj Hospital, Thailand. Data were collected from HIV-infected adults, initiated with highly active antiretroviral therapy (HAART) with initial CD4+ <200 cells/mm3. Results: Overall, 217 patients had a median initial CD4+ of 83 cells/mm3 (interquartile range: 33.5–150.5) (range: 0–199), most of the initial HAART regimen was non-nucleoside reverse transcriptase inhibitors based containing tenofovir disoproxil fumarate (94.94%), and 104 patients (47.93%) received chemoprophylaxis. The incidence between patients who received and did not receive prophylaxis found no statistically significant difference (p = 0.133). Only one event was found in a severely immunocompromised patient who did not receive the prophylaxis. The absolute risk reduction of primary PCP incidence, and rate of ADRs was 0.89% (95% confidence interval, −0.84, 2.61) and 10.58% in patients who received the chemoprophylaxis, respectively. Conclusion: The initiation of HAART in HIV-infected patients who had the initial CD4+ cell count <200 cells/mm3 may impact on reducing the risk of developing primary PCP. Aside from the patients who received the prophylaxis, most of the adverse reactions were skin disorders.

Synthesis, Docking, And Molecular Dynamic Study Of Hydrazones Compounds To Search Potential Inhibitor For Breast Cancer Mcf-7, Jasril, Yuana Nurulita, Nur Afriana, Ihsan Ikhtiarudin, Neni Frimayanti

The Thai Journal of Pharmaceutical Sciences

Introduction: Hydrazones have been reported for various biological activities, such as anticancer. The presence of the azomethine group (-NHN=CH-) makes these compounds as one of the important classes in many synthetic products. Objective: The aim of this work is to explore the potential of halogenated hydrazones series as breast cancer inhibitors. Methods: In this study, some series of halogenated hydrazones have been synthesized through condensation reaction between halogenated benzaldehydes and phenylhydrazine under microwave irradiation. The structures of the halogenated hydrazoes were confirmed by ultraviolet, fourier-transform infrared, NMR, and gas chromatography-mass spectrometry spectroscopic data. The in silico studies i.e. docking and …

A Qualitative Study Of Nimbyism For Waste In Smaller Urban Areas Of A Low-Income Country, Mzuzu, Malawi., Rochelle H. Holm, Brighton A. Chunga, Adrian Mallory, Paul Hutchings, Alison Parker

Faculty and Staff Scholarship

When waste management infrastructure is built, there can be resistance from the local affected populations, often termed the Not in My Backyard (NIMBY) phenomenon. This study aims to understand the forms of resistance that may develop in such contexts, focusing on 2 solid waste and 1 liquid waste management site within Mzuzu City, Malawi. At the newest solid waste site, community resistance had grown to the extent that the site was reportedly destroyed by the local community. Interviews and observations of the sites are complemented by examining historic and recent satellite images. It was found that, at the new solid …

Seaweed Polysaccharide In Food Contact Materials (Active Packaging, Intelligent Packaging, Edible Films, And Coatings), Kalpani Perera, Shubham Sharma, Dileswar Pradhan, Amit Jaiswal, Swarna Jaiswal

Articles

Food contact materials (FCMs) are materials that come in contact with food products such as food packaging which play a significant role in food quality and safety. Plastic, which is a major food packaging material, harms the ecosystem, wildlife, and the environment. As a result, numerous researches have been in progress on alternative polymers, which have similar properties as plastic but are also environmentally friendly (biodegradable). In recent years, the utilization of seaweed polysaccharides has piqued interest due to their biodegradability, non-toxicity, antioxidant capabilities, and excellent film formation ability. However, it has a number of drawbacks such as low tensile …

Structure Based Prediction Of A Novel Gpr120 Antagonist Based On Pharmacophore Screening And Molecular Dynamics Simulations, Ajay Pal Mr, Gemma K. Kinsella, James Curtin

Articles

The G-protein coupled receptor, GPR120, has ubiquitous expression and multifaceted roles in modulating metabolic and anti-inflammatory processes. Recent implications of its role in cancer progression have presented GPR120 as an attractive oncogenic drug target. GPR120 gene knockdown in breast cancer studies revealed a role of GPR120-induced chemoresistance in epirubicin and cisplatin-induced DNA damage in tumour cells. Higher expression and activation levels of GPR120 is also reported to promote tumour angiogenesis and cell migration in colorectal cancer. Some agonists targeting GPR120 have been reported, such as TUG891 and Compound39, but to date development of small-molecule inhibitors of GPR120 is limited. …

Connectivity: Insights From The U.S. Long Term Ecological Research Network, David M. Iwaniec, Michael Gooseff, Katharine N. Suding, David Samuel Johnson, Daniel C. Reed, Debra P. C. Peters, Byron Adams, John E. Barrett, Brandon T. Bestelmeyer, Max C. N. Castorani, Elizabeth M. Cook, Melissa J. Davidson, Peter M. Groffman, Niall P. Hanan, Laura F. Huenneke, Pieter T. J. Johnson, Diane M. Mcknight, Robert J. Miller, Gregory S. Okin, Daniel L. Preston, Andrew Rassweiler, Chris Ray, Osvaldo E. Sala, Robert L. Schooley, Timothy Seastedt, Marko J. Spasojevic, Enrique R. Vivoni

Advanced Science Research Center

Ecosystems across the United States are changing in complex and surprising ways. Ongoing demand for critical ecosystem services requires an understanding of the populations and communities in these ecosystems in the future. This paper represents a synthesis effort of the U.S. National Science Foundation-funded Long-Term Ecological Research (LTER) network addressing the core research area of “populations and communities.” The objective of this effort was to show the importance of long-term data collection and experiments for addressing the hardest questions in scientific ecology that have significant implications for environmental policy and management. Each LTER site developed at least one compelling case …

Comparative Studies On Biochemical And Pharmacological Profiles Of Unfractionated Heparins & Their Depolymerized Derivatives From Bovine, Ovine And Porcine Origins, Ahmed Kouta

Dissertations

Heparin and heparin related drugs have remained the anticoagulant of choice for medical and surgical indications. These drugs are comprised of poly-component sulfated chains of varying length and biophysical structure with direct and indirect pharmacological effects. Heparins produce their therapeutic effects by multiple mechanisms involving both the cellular and humoral targets. These drugs represent natural products which are isolated from mammalian tissue rich in mast cells. Currently used heparin and LMWHs are obtained from porcine mucosal tissue. Other animal sources including bovine and ovine tissues also provide additional sources for the manufacturing of heparins. While there may be microchemical and …

Cardioprotective Extracellular Vesicles Derived-Micrornas: Sorting Mechanisms And Functions, Anh P. Phan

Dissertations

Extracellular vesicles (EVs) are nano-size membrane bound vesicles that are derived from the fusion of multivesicular endosomes with the plasma membranes. EVs have important roles in intercellular communication through the transfer of their unique cargoes including RNA, DNA and protein molecules to recipient cells. Mesenchymal stem cell (MSC)-derived EVs have been shown to reduce infarct size and reduce the progress of heart failure after cardiac ischemia/reperfusion (I/R) injury in animal models. Small non-coding RNAs such as microRNA (miRNA) have been indicated as one of the active components that mediate the beneficial effects of MSC-derived EVs. However, the selective packaging mechanisms …

Elucidation Of Multi-Origin Inula Helenium L. For Antimicrobial Activity And Heavy Metal Profiling As An Exemplar For The Use And Regulation Of Plants As Antibiotics., Ciara Ruth Kenny

Theses

An impending post-antibiotic era looms, thus new sources of therapeutic chemical entities are crucial to sustain effective antimicrobial chemotherapy worldwide. Plant natural products are a source of accessible, structurally diverse compounds that provide therapeutic potential. The pharmacological applications of plants in medicine can be guided by the attestation of traditional use or the application of this knowledge to uncover new leads in the drug discovery process. The range of modified in vitro methods commonly used to investigate preclinical antimicrobial efficacy of plant-derived natural products, and the associated limitations and challenges in the provision of new antimicrobial drugs from plants is …

Investigating Cannabinoid Type-1 Receptor (Cb1r) Positive Allosteric Modulators (Pams) In Mouse Models Of Overt Cannabimimetic Activity, Subjective Drug Effects, And Neuropathic Pain, Jayden Elmer

Theses and Dissertations

Chronic pain affects between 20 and 30 percent of the adult population in western countries and represents a wide array of specific etiologies (Berge, 2011). Neuropathic pain secondary to traumatic nerve injury, chemotherapeutic toxicity, or diseases (e.g., diabetes mellitus) is often refractory to conventional analgesics, with patients receiving less than 50% pain relief compared to placebo (Finnerup et al. 2010). The endocannabinoid system has shown potential as a therapeutic target for neuropathic pain wherein CB1 agonism via administration of exogenous agonists or pharmacological blockade of endocannabinoid catabolic enzymes exhibits efficacy in reversing allodynia in the chronic constriction injury (CCI) model …

Pharmacophoric Evaluation Of 5-Ht2a And 5-Ht2b Serotonin Recpeptors, Prithvi Hemanth

Theses and Dissertations

Serotonin (5-HT) receptors represent a class of receptors involved in a variety of physiological processes including regulation of mood, perception, cognition, appetite, and heart function, and thus serve as drug targets of several drugs such as antipsychotic agents, hallucinogenic drugs, and appetite suppressant drugs. Due to the structural similarity of certain 5-HT receptor subtypes, particularly 5-HT₂ receptors (5-HT_2A, 5-HT_2B receptors) determination and refinement of pharmacophore models of these receptor subtypes can greatly improve the therapeutic efficacy of drugs that target them.

The goals of this study were to define and/or refine existing pharmacophore models for 5-HT …

Dendrimer-Based Antibiotics For The Treatment Of Bacterial Biofilm In Cystic Fibrosis (Cf), Younan Ma

Theses and Dissertations

Pseudomonas aeruginosa (PA) is the predominant pathogen in chronic lung infections of cystic fibrosis (CF) patients. The most important mechanism of adaptation of PA to host defense and antibiotic treatment is the formation of biofilms within the mucus layer covering the lung bronchi. The effectiveness of antibiotics such as aminoglycosides is significantly attenuated by their limited penetration through thick mucus and embedded biofilm matrix in patients’ lung. Inhaled tobramycin (Tobra), which is the most commonly used antibiotics in the treatment of PA infections for CF patients, is usually found to be in very high concentration in patients’ lung, and yet …

Interclass Gpcr Heteromerization Affects Localization And Trafficking, Rudy Toneatti

Theses and Dissertations

Class A serotonin (5-hydroxytryptamine) 2A (5-HT_2AR) and class C metabotropic glutamate 2 receptors (mGluR2) are seven transmembrane receptors (7TMRs or G protein-coupled receptors – GPCRs) involved in multiple neuropsychiatric disorders including schizophrenia. Previous findings from our laboratory reported that 5-HT_2AR and mGluR2 are dysregulated in the prefrontal cortex of patients suffering from this psychiatric condition, although 5-HT_2AR’s expression was recovered in antipsychotic-medicated patients. Genome-wide association studies on schizophrenia reported that endosomal trafficking that regulates cell surface abundance of another 7TMR implicated in this disease (dopamine D2 receptor) can be altered. Ligand-activated receptors, including the …

The Cb1 Receptor Positive Allosteric Modulator, Zcz011, Attenuates Naloxone-Precipitated Withdrawal Signs In Oxycodone-Dependent Mice And Inhibits Small Intestinal Transit In Mice, Julien Dodu

Theses and Dissertations

The endogenous cannabinoid system tightly regulates a myriad of physiological and pathophysiological functions. Effects of cannabinoids in ameliorating opioid withdrawal signs has been known for decades. Naloxone precipitates several withdrawal signs (e.g., diarrhea, weight loss, jumps, paw flutters, and head shakes) in opioid dependent rodents. ∆⁹-tetrahydrocannabinol (THC) has been shown to ameliorate opioid withdrawal in mice through the activation of cannabinoid type-1 (CB₁) receptors. Inhibition of the endocannabinoid degradative enzymes also attenuates these withdrawal signs (i.e., diarrhea, weight loss, jumps, paw flutters, and head shakes) in opioid-dependent mice. Specifically, inhibition of fatty acid amide hydrolase (FAAH), …

Nebulizer-Based Systems To Improve Pharmaceutical Aerosol Delivery To The Lungs, Benjamin M. Spence

Theses and Dissertations

Combining vibrating mesh nebulizers with additional new technologies leads to substantial improvements in pharmaceutical aerosol delivery to the lungs across therapeutic administration methods. In this dissertation, streamlined components, aerosol administration synchronization, and/or Excipient Enhanced Growth (EEG) technologies were utilized to develop and test several novel devices and aerosol delivery systems. The first focus of this work was to improve the poor delivery efficiency, e.g., 3.6% of nominal dose (Dugernier et al. 2017), of aerosolized medication administration to adult human subjects concurrent with high flow nasal cannula (HFNC) therapy, a form of continuous-flow non-invasive ventilation (NIV). The developed Low-Volume Mixer-Heater (LVMH) …

Influence Of 2,5-Dimethoxy-4-Iodoamphetamine (Doi) On Ethanol Preference And Consumption In C57bl/6 Male Mice, Alaina M. Jaster, Sam Gottlieb, Michael Miles, Javier González-Maeso

Graduate Research Posters

Substance use disorders (SUD) account for a large number of mental health diagnosis in the United States and around the world. Approximately 13.6 million adults 26 or older and 5.1 million young adults (ages 18-24) battled with a SUD in 2017. Alcohol Use Disorder (AUD) alone effects nearly 6% of the adult population within the United States. This creates a substantial burden on the individual, with alcohol being the third-leading cause of preventable death in the United States. Few treatments for AUD exist, with no new FDA-approved therapeutic treatments within the last 15 years. Additionally, the limited treatments we do …

High Throughput Analysis To Study Emerging Pollutants And Nanoparticle Fate In Biological Systems, Xiaolong He

Doctoral Dissertations

”The increasing applications of emerging and fugitive contaminants (EFCs) and engineered nanoparticles (ENPs) attract significant research interest for their potential risks to human health and the environment. In order to assess the health risks of these emerging contaminants, rapid and reliable analytical methods to measure the concentrations and fates of these contaminants are imperative. This dissertation focuses on the developments of advanced analytical methods and their applications to study those emerging contaminants in crop plant and simulated gastric fluid (SGF). Three types of mass spectrometry based methodologies have been developed, one is freeze-thaw/centrifugation extraction followed by high performance liquid chromatography …

The Effects Of Fluoride On Macrophage Thp-1 Cell Apoptosis, Jessica Heims

Honors Program Theses

Fluoride is an earthly mineral that occurs naturally both in the sedimentary earth as well as in the human body. The main biological function of fluoride in the human body is to enhance bone structure, as well as prevent the decay of teeth. This mineral has been used by dentists and public health officials to artificially introduce an extra layer of protection through the means of fluoride-enriched public water supplies and toothpastes. By using extra levels of fluoride, dentists have been able to help patients prevent future cavities and dental diseases. Although most dentists highly encourage strategic consumption of these …

Exploring Early Signaling Associated With Complex Stressors, Julia A. Penatzer

Graduate Theses, Dissertations, and Problem Reports (ETD)

Humans are constantly exposed to a vast number of stressors in our everyday lives from social interactions to physical activity to chemical exposures, to name a few. These stressors have significant impacts on an individual, from the cellular to whole organismal level. The body contains an intricate communication system that elicits a number of both biological and physiological responses as it attempts to maintain homeostasis. Observing these responses to stressors, can offer insight into a number of outcomes, which can be beneficial (increasing life longevity) or detrimental (leading to a disease state). By measuring specific biological adaptations at particular time …