Pharmacology, Toxicology and Environmental Health Commons^™

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

Chemistry: Faculty Publications and Other Works

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 ~1622 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 …

Lipid Based Nanoparticles As A Novel Treatment Modality For Hepatocellular Carcinoma: A Comprehensive Review On Targeting And Recent Advances, Khaled Mahmoud, Shady Swidan, Mohamed A. El-Nabarawi, Mahmoud H. Teaima

Pharmacy

Liver cancer is considered one of the deadliest diseases with one of the highest disease burdens worldwide. Among the different types of liver cancer, hepatocellular carcinoma is considered to be the most common type. Multiple conventional approaches are being used in treating hepatocellular carcinoma. Focusing on drug treatment, regular agents in conventional forms fail to achieve the intended clinical outcomes. In order to improve the treatment outcomes, utilizing nanoparticles—specifically lipid based nanoparticles—are considered to be one of the most promising approaches being set in motion. Multiple forms of lipid based nanoparticles exist including liposomes, solid lipid nanoparticles, nanostructured lipid carriers, …

The Unexpected Influence On Talent From Air Pollution, Singapore Management University

Perspectives@SMU

CUHK research shows air pollution in China is driving educated and skilled company executives to move away from highly polluted areas, hampering the performance of firms located there

Rising Recess Temperatures: Quantifying The Cooling Effect Of School Parks, Nicholas Kendall, Xuhui Lee

Library/Life Sciences Undergraduate Poster Competition 2022

Many schools in the US are currently placed in urban heat islands. Children attending these schools are thought to be at greater risk to heat stress related health concerns. We used mobile heat sensors to see if there was a quantifiable difference between the playgrounds and parks within and between two schools with differing park sizes.

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 …

Case Report: Pharmacogenetics Applied To Precision Psychiatry Could Explain The Outcome Of A Patient With A New Cyp2d6 Genotype, Elena Marcos-Vadillo, Lorena Carrascal-Laso, Ignacio Ramos-Gallego, Andrea Gaedigk, Belén García-Berrocal, Eduardo Mayor-Toranzo, Alfonso Sevillano-Jiménez, Almudena Sánchez, María Isidoro-García, Manuel Franco-Martín

Manuscripts, Articles, Book Chapters and Other Papers

Precision medicine applied to psychiatry provides new insight into the promising field of precision psychiatry. Psychotic disorders are heterogeneous, complex, chronic, and severe mental disorders. Not only does the prognosis and the course of the disease vary among patients suffering from psychotic disorders, but the treatment response varies as well. Although antipsychotic drugs are the cornerstone of the treatment of schizophrenia, many patients only partially respond to these drugs. Furthermore, patients often experience adverse events which can lead to poor treatment adherence. Interindividual variability in drug response could be related to age, gender, ethnicity, lifestyle factors, pharmacological interactions, obesity, and …

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.

Implementation Of A Drive-Through Covid-19 Mass Vaccination Site: Experiences From Louvax–Broadbent In Louisville, Kentucky, Ruth Carrico, Sarah Beth Hartlage, Valenchia Brown Msn, Aprn, Fnp-C, Sarah M. Bishop, Luanne Didelot, William Hayden, Beverly Williams Coleman, Sarah Tan, Delanor Manson, Kellie Kane, Dawn Balcom, Paul Kern

The University of Louisville Journal of Respiratory Infections

Background: Response to the COVID-19 pandemic has required innovative approaches to vaccination, including methods to rapidly and safely immunize communities. A major challenge to such a response involved access to untapped healthcare worker resources. The Louisville, Kentucky, response involved the use of a large volunteer workforce to supplement local public health employees in planning and implementing a large-scale drive-through vaccination event. The objective of this manuscript was to outline processes involved in training a mass immunization workforce and implementating a large-scale COVID-19 community vaccination.

Approach: Competency-based and standardized training was provided for every volunteer before working their shift. Volunteers worked …

In Vitro Toxicological Evaluation Of Mesoporous Silica Microparticles Functionalised 1 With Carvacrol And Thymol, Cristina Fuentes, Ana Fuentes, Hugh Byrne, José Barat, María José Ruiz

Articles

The cytotoxicity of carvacrol- and thymol- functionalised mesoporous silica microparticles (MCM-41) was assessed in the human hepatocarcinoma cell line (HepG2). Cell viability, lactate dehydrogenase (LDH) activity, reactive oxygen species (ROS) production, mitochondrial membrane potential (ΔΨm), lipid peroxidation (LPO) and apoptosis/necrosis analysis were used as endpoints. Results showed that both materials induced cytotoxicity in a time and concentration-dependent manner, being more cytotoxic than free essential oil components and bare MCM-41. This effect was caused by the cell-particle interactions and not from degradation products released to the culture media, as demonstrated in the extract dilution assays. LDH release was seen to be …

Fate And Effect Of Food-Grade Titanium Dioxide Particles/Polystyrene Nanoplastics On Nutrients Bioaccessibility Of Food In The Simulated Human Gastrointestinal Tract, Chunyang Li

Doctoral Dissertations

Food grade titanium dioxide particles (E171), as whitening agent, are commonly used in chewing gums, candies, sauces, salad dressings, and powdered milk. Recently, nanoplastics (NPs) (defined as < 1 µm), which are degraded from plastic debris undergoing environmental process, have received global attention. Because nanoplastics are ubiquitous in aquatic and terrestrial systems, and have been detected in marine animals, table salts, drinking water, and air. Thus, the presence of E171 as additives in the food, and the nanoplastics in food chains, both pose potential risks to human health through retarded processes in the gastrointestinal tract (GIT). However, the knowledge about the fate of E171 or nanoplastics and their impact on digestive enzymes activity or nutrient bioaccessiblity are currently limited. Therefore, it is necessary to investigate potential impacts of E171 or nanoplastics on digestion processes and nutrient bioaccessibility in the simulated human gastrointestinal tract, which includes mouth, stomach and intestinal phases, to mimic the digestion processes of food incubating with E171 or polystyrene (PS) nanoplastics. The objectives of my dissertation and major findings are presented below: 1) The impacts of E171 on lipid digestion and vitamin D₃ (VD₃) bioaccessibility encapsulated within oil-in-water emulsions in a simulated human gastrointestinal tract model were explored; 2) The impacts of E171 on the bioaccessibility of minerals (Ca, K, Mg, Fe, Mn, Zn, P and S) released from spinach leaves using a simulated human digestion tract were investigated; 3) The impacts of various concentrations or different functional group (-COOH, -NH₂) of PS NPs on the starch hydrolysis in the simulated …

Body Mass Index (Bmi): A Screening Tool Analysis, Deepesh Khanna, Cadynce Peltzer, Payal Kahar, Mayur S. Parmar

HPD Articles

Body mass index (BMI), a measurement based on a person's height and weight, allows the classification of individuals into categories such as obese or overweight. With these classifications, we can assess risk for hypertension, diabetes, cancer, hypercholesterolemia, and other chronic diseases. Furthermore, childhood BMI serves as a prediction method for health and disease later in life. Along with BMI, researchers also study waist circumference and waist-to-hip ratio in correlation with the above-mentioned chronic illnesses. This brief review explores the associations between body mass index, waist circumference, and the waist-hip ratio as measurements and their capability as predictors for persistent conditions …

The Environment Under The Knife: A Review Of Current Eco-Surgical Strategies And Recommendations For Pakistan, Russell Seth Martins, Edward Anthony Joseph, Javeria Tariq, Namrah Aziz, Saulat H. Fatimi

Medical College Documents

The healthcare sector at its core is based on the fundamentals belief to do no harm and bring about betterment in the lives of the people. Paradoxically, hospitals are one of the leading contributors to pollution, greenhouse gas (GHG) emissions and toxic waste material worldwide. Surgical care delivery is quite resource intensive, consuming significant amount of energy and equipment as well as producing large quantities of waste. With climate change being a global priority, it is crucial that hospitals re-evaluate the environmental impact of such practices. The current review was planned to identify areas of improvement in surgical care in …

Repurposing Metformin And Antifolates For The Treatment Of Hepatocellular Carcinoma, Sherouk Mohamed Tawfik

Theses and Dissertations

Hepatocellular carcinoma (HCC), one of the most prevalent types of cancers worldwide, continues to maintain high levels of resistance to standard therapy. As clinical data revealed poor response rates, the need for developing new methods has increased to improve the overall wellbeing of patients with HCC. Due to its safety, wide availability and previously reported anti-cancer effects, metformin (MET) serves to be a possible therapeutic agent when combined with other well-known anti-cancer agents. The aim of this study was to investigate the potential anti-cancer effects of MET, an anti-diabetic agent, when combined with two antifolate drugs: trimethoprim (TMP) or methotrexate …

Selective Gsk3Β Inhibition Mediates An Nrf2-Independent Anti-Inflammatory Microglial Response, Mohamed H. Yousef

Theses and Dissertations

Glycogen Synthase Kinase 3 (GSK3) is associated with the proinflammatory phenotype of microglia and has been shown to act in concert with Nuclear factor kappa B (NF-κB). . GSK3 is also a suppressor of Nuclear factor erythroid 2-related factor 2 (Nrf2), the principal regulator of redox homeostasis. Agreeing with the oxidative paradigm of aging, Nrf2 is often deregulated in parainflammatory and neurodegenerative diseases. In this study, we aimed to explore a multimodal disease-modifying utility of GSK3 inhibition, beyond neuronal proteopathologies, Furthermore, we aimed to underscore the difference in therapeutic value between the two GSK3 paralogs by isoform-selective chemical inhibition.

The …

Surveillance Of Rnase P, Pmmov, And Crassphage In Wastewater As Indicators Of Human Fecal Concentration Across Urban Sewer Neighborhoods, Louisville, Kentucky, R. H. Holm, M. Nagarkar, R. A. Yeager, D. Talley, A. C. Chaney, J. P. Rai, A. Mukherjee, S. N. Rai, A. Bhatnagar, T. Smith

Faculty Scholarship

Wastewater surveillance has been widely used as a supplemental method to track the community infection levels of severe acute respiratory syndrome coronavirus 2. A gap exists in standardized reporting for fecal indicator concentrations, which can be used to calibrate the primary outcome concentrations from wastewater monitoring for use in epidemiological models. To address this, measurements of fecal indicator concentration among wastewater samples collected from sewers and treatment centers in four counties of Kentucky (N = 650) were examined. Results from the untransformed wastewater data over 4 months of sampling indicated that the fecal indicator concentration of human ribonuclease P (RNase …

Measurement Of Binding Affinity And Receptor Activation Of A Novel Curcumin Analog, Cis-Trans Curcumin, At Adenosine Receptors A1, A2a, A2b, And A3, Luke James Hamilton

Biology Theses, Dissertations, and Student Creative Activity

Vanilloid phytochemicals (VPs), which contain the 4-hydroxy-3-methoxybenzyl group, have consistently been shown to alleviate pain. All four of the adenosine receptor (AR) subtypes mediate pain and have been targeted by pharmacologists to generate new therapeutics for pain. However, despite the fact that both VPs and ARs are connected to pain relief, only a few studies have described the interaction between VPs and ARs. Furthermore, the few studies that have been done have all been performed in vivo, with no assessment of binding affinity and receptor activation in vitro. In this study, photochemical methods were used to generate a novel isomer …

Results Of A Phase 1, Randomized, Placebocontrolled First-In-Human Trial Of Griffithsin Formulated In A Carrageenan Vaginal Gel, Natalia Teleshova, Maria J. Keller, José A. Fernández Romero, Barbara A. Friedland, George W. Creasy, Marlena G. Plagianos, Laurie Ray, Patrick Barnable, Larisa Kizima, Aixa Rodriguez, Nadjet Cornejal, Claudia Melo, Gearoff Cruz Rodriguez, Sampurna Mukhopadhyay, Giulia Calenda, Shweta U. Sinkar, Thierry Bonnaire, Asa Wesenberg, Shimin Zhang, Kyle Kleinbeck, Kenneth Palmer, Mohcine Alami, Barry R. O'Keefe, Patrick Gillevet, Hong Hur, Yupu Liang, Gabriela Santone, Raina N. Fichorova, Tamara Kalir, Thomas M. Zydowsky

Publications and Research

HIV pre-exposure prophylaxis (PrEP) is dominated by clinical therapeutic antiretroviral (ARV) drugs. Griffithsin (GRFT) is a non-ARV lectin with potent anti-HIV activity. GRFT’s preclinical safety, lack of systemic absorption after vaginal administration in animal studies, and lack of cross-resistance with existing ARV drugs prompted its development for topical HIV PrEP. We investigated safety, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of PC-6500 (0.1% GRFT in a carrageenan (CG) gel) in healthy women after vaginal administration. This randomized, placebo-controlled, parallel group, double-blind first-in-human phase 1 study enrolled healthy, HIV-negative, non-pregnant women aged 24–45 years. In the open label period, all participants (n …

Effects Of Foliar Application Of Zno Nanoparticles On Lentil Production, Stress Level And Nutritional Seed Quality Under Field Conditions, Marek Kolenčík, Dávid Ernst, Matej Komár, Martin Urík, Martin Šebesta, Ľuba Ďurišová, Marek Bujdoš, Ivan Černý, Juraj Chlpík, Martin Juriga, Ramakanth Illa, Yu Qian, Huan Feng, Gabriela Kratošová, Karla Čech Barabaszová, Ladislav Ducsay, Elena Aydın

Department of Earth and Environmental Studies Faculty Scholarship and Creative Works

Nanotechnology offers new opportunities for the development of novel materials and strategies that improve technology and industry. This applies especially to agriculture, and our previous field studies have indicated that zinc oxide nanoparticles provide promising nano-fertilizer dispersion in sustainable agriculture. However, little is known about the precise ZnO-NP effects on legumes. Herein, 1 mg·L⁻¹ ZnO-NP spray was dispersed on lentil plants to establish the direct NP effects on lentil production, seed nutritional quality, and stress response under field conditions. Although ZnO-NP exposure positively affected yield, thousand-seed weight and the number of pods per plant, there was no statistically significant …