Pharmacology, Toxicology and Environmental Health Commons^™

Discovering New Potential Inhibitors To Sars-Cov-2 Rna Dependent Rna Polymerase (Rdrp) Using High Throughput Virtual Screening And Molecular Dynamics Simulations., Dylan Brunt, Phillip M Lakernick, Chun Wu

College of Science & Mathematics Departmental Research

RNA dependent RNA polymerase (RdRp), is an essential in the RNA replication within the life cycle of the severely acute respiratory coronavirus-2 (SARS-CoV-2), causing the deadly respiratory induced sickness COVID-19. Remdesivir is a prodrug that has seen some success in inhibiting this enzyme, however there is still the pressing need for effective alternatives. In this study, we present the discovery of four non-nucleoside small molecules that bind favorably to SARS-CoV-2 RdRp over the active form of the popular drug remdesivir (RTP) and adenosine triphosphate (ATP) by utilizing high-throughput virtual screening (HTVS) against the vast ZINC compound database coupled with extensive …

An In Silico Study Of The Delta Opioid Receptor Using Small Molecules, Emily Dean

Theses and Dissertations

The DOR is the least studied out of the three opioid receptors (Mu, Kappa, and Delta). The most is known of the Mu Opioid receptor (MOR) and the drugs that target it have led to the global opioid epidemic due to their adverse effects of tolerance and addiction. The DOR is not known for the same adverse effects and therefore, is a promising pharmacological target for the development of new opioid ligands. In this thesis, molecular modeling, simulations and other computational methods are introduced in Chapter 1 where these methods are used to study the activation mechanism of DOR (Chapter …

Esterase Mediated Insecticide Resistance In The Southern House Mosquito, Culex Quinquefasciatus, Vivek Pokhrel

LSU Doctoral Dissertations

Much is known about the development of insecticide resistance associated with targeted application against insect populations. However, off-target selection by applications of insecticides in agricultural and residential sites also impacts development of insecticide resistance and is understudied. Similarly, the impact of selecting one life stage of mosquitoes on the insecticide susceptibility of different life stages is largely unknown. The first part of this study shows that susceptibility to chlorantraniliprole, which is applied in rice and sugarcane fields in LA, decreased (5.7 to12-fold) in populations of Culex quinquefasciatus collected from near these fields compared to a reference field strain. In addition, …

The Presence Of Microcystin In The Northwest Indiana Watershed, Breeann Mild

The Journal of Purdue Undergraduate Research

No abstract provided.

Developmental Behavioral Alterations Following Lead (Pb) Exposure In The Zebrafish Model System, Jenny Chen

The Journal of Purdue Undergraduate Research

No abstract provided.

Behavioral Alterations Following Exposure To A Mixture Of Lead And Atrazine During Early Development In The Zebrafish Model System, Anusha Kv Lakshmi Dharmavathi

The Journal of Purdue Undergraduate Research

Lead (Pb) and atrazine (ATZ) are hazardous environmental toxicants that can exist as a mixture in potable water. Numerous single chemical studies on Pb and ATZ support adverse health outcomes, including neurotoxicity, but mixture studies are limited. Th e aim of this study is to test the hypothesis that Pb and ATZ mixtures result in a greater than additive toxicity, causing increased adverse health outcomes than single chemical exposures. Th e zebrafish model system was exposed to 3 or 30 ppb (µg/L) ATZ, 10 ppb (equivalent to 0.1 µg/dL) or 100 ppb Pb, along with mixtures of each beginning at …

Supporting The Protect Initiative, Josh Lefton, Jackson Murray, Ahmed Thabet, Sriram Baireddy, Prakash Shukla, Mridul Gupta, Reagan Becker, Julie Ertle, Tony Doan, Aerin Yang

Purdue Journal of Service-Learning and International Engagement

Recently, medication dosage errors have received more political and media attention. Dosage errors are the most common medical errors, affecting about 1.5 million people annually.

Furthermore, U.S. poison-control centers reported more than 200,000 cases per year of medication errors. These cases result in medical costs of around $3.5 billion, and children under 6 years old constitute approximately 30% of these cases.

The PROTECT Initiative (Preventing Overdoses and Treatment Errors in Children Taskforce) was launched in 2008 as a collaborative effort between public health agencies and patient advocates to minimize dosage errors.

In alignment with the PROTECT Initiative effort, this project …

Acute Toxicity Of Atrazine, Alachlor, And Chlorpyrifos Mixtures To Honey Bees, Christopher J. Fellows, Troy D. Anderson, Daniel R. Swale

Department of Entomology: Faculty Publications

The acute toxicity of chlorpyrifos and chlorpyrifos-oxon (organophosphorothioate insecticides) was examined alone and in combination with atrazine (triazine herbicide) and alachlor (chloroacetanilide herbicide) to honey bees (Apis mellifera). Atrazine and alachlor were observed to not be acutely toxic to bees at doses up to 10 and 4 μg per bee, respectively. However, atrazine significantly increased chlorpyrifos toxicity by 3-fold while reducing chlorpyrifos-oxon toxicity by 1.8-fold. These changes in toxicity are correlated with significant 1.3- and 1.2-fold inhibition of acetylcholinesterase (AChE) activity in bees exposed to chlorpyrifos and chlorpyrifos-oxon, respectively. Atrazine significantly increased cytochrome P450, general esterase, and glutathione …

Hepatotoxic And Nephrotoxic Effects Of Chronic Exposure To Vernonia Cinerea Crude Extract On Wistar Rats, Thularath Toommakorn, Sajee Waramit, Patchara Danaisawadi, Kantimanee Pradermwong

The Thai Journal of Pharmaceutical Sciences

Vernonia cinerea L. (VC) has been used for smoking cessation and decreased appetite in Thailand. However, the safety of this plant concerning long-term consumption has never been reported. A 6-month toxicity study of VC water crude extract (VCWE) was performed in both genders of Wistar rats at doses of 15, 150, and 1500 mg/kg body weight/day orally. Recovery group received 1500 mg/kg for 6 months and then extended for 14 days without the extract. It was found that the males could not tolerate the highest dose of VCWE. There was no effect on bodyweight, relative organ weight, nor hematological parameters …

Impact Of A Digital Educational Program On The Health Literacy And Perceived Drug Teratogenic Risk Of Diabetic Pregnant Women Attending A Malaysian Teaching Hospital, Sami Al-Shakhshir, Syed Azhar Sulaiman, Mohd Pazudin Ismail, Mahmoud S. Alhaddad, Yaser Mohammed Al-Worafi, Islam M. Ashram

The Thai Journal of Pharmaceutical Sciences

ABSTRACTObjectives: The study aimed to identify the impact of clinical pharmacist’s digital educational program on health literacy and drug teratogenicity risk among Malaysian diabetic pregnant women. Methods: A quasi-experimental study was undertaken at the antenatal clinic at Universiti Sains Malaysia Hospital (HUSM) in Malaysia. The study was carried out with 138 diabetic pregnant women who were conveniently interviewed to measure their health literacy and teratogenic risk perceptions before and after educational program which was conducted using WhatsApp application. Descriptive and inferential analyses were performed using SPSS version 22. P-values of less than 0.05 were considered significant. Results: Most participants had …

Anti-Inflammatory Activity Of Phenolic-Rich Fraction Of Pandanus Tectorius Fruits Via Reduction Of No Production On Lipopolysaccharide-Stimulated Raw264.7 Cell Lines And Formalin-Induced Paw Oedema, Yosie Andriani, Nadia Madihah Ramli, Noor Suryani Musa, Kanwal Kanwal, Habsah Mohamad, Hermansyah Amir, Murni Nur Islamiah Kassim, Desy Fitrya Syamsumir, Tengku Sifzizul Tengku Muhammad, Suvik Assaw

The Thai Journal of Pharmaceutical Sciences

Background: The current study is the first study that investigated the potential of phenolic-rich fraction of Pandanus tectorius fruits as an anti-inflammatory agent. The fruit is rich in phenolic compounds, especially from the flavonoids group. Phenolics are known to contribute to an anti-inflammatory activity. Objectives: The first objective of the study was to evaluate the anti-inflammatory potency of phenolic-rich fractions of P. tectorius fruits by in vitro and in vivo studies. The second was to investigate the cytotoxicity against RAW264.7 cell lines, antioxidant, and phenolic contents to support the experiment. Materials and Methods: Sample fractionation was done with hexane, ethyl …

Citrus Aurantium Peels Secondary Metabolites Prevents Cell Senescence On Human Fibroblasts Cells By In Vitro And Bioinformatics Studies, Nur Dina Amalina, Sri Wahyuni, Harjito H, Meiny Suzery, Bambang Cahyono

The Thai Journal of Pharmaceutical Sciences

Aging is a medical problem affecting about 800 million people worldwide. However, the molecular mechanism of aging and aging-related disease has not yet been explored. Skin aging is a complex biological process primarily due to cellular senescence. Cellular senescence is an irreversible growth arrest that caused tissue to lose their cell-specific functionality, secreting pro-tumorigenic and pro-inflammatory cytokines, which eventually causes cancer. Citrus aurantium-derived secondary metabolites, including hesperidin, hesperetin, tangeretin, naringenin, nobiletin, and quercetin, are of vital importance to inhibiting aging due to their active properties. However, the effect of C. aurantium-derived secondary metabolites on the cells senescence and its molecular …

Synthesis, Docking Studies, Admet Prediction, And Antimicrobial Evaluation Of Coumarin-Oxadiazole Hybrids, Fabin Asmath Maziyuna, Abhishek Kumar, Pankaj Kumar

The Thai Journal of Pharmaceutical Sciences

The overuse and misuse of marketed antimicrobial agents developed drug resistance, which has become a significant problem worldwide. A series of new coumarinyl-oxadiazole Schiff base derivatives were designed and synthesized. These synthesized molecules synthesis of coumarinyl-oxadiazole schiff base derivatives (FP1-FP7) were characterized using Infrared spectroscopy, proton nuclear magnetic spectroscopy, and mass spectroscopy and evaluated for their antibacterial potential against Gram-negative (Escherichia coli, Pseudomonas aeruginosa) and Gram-positive (Bacillus subtilis, Staphylococcus aureus) bacterial strain by measuring minimum inhibitory concentration values. Among the synthesized compounds, FP6 was found to be the best antibacterial agent having concentration values of 3.12 and 6.25 μg/ml against …

The Synergistic Antitumor Effects Of Curcuma Longa And Phyllanthus Niruri Extracts On Promoting Apoptotic Pathways In Breast Cancer Stem Cells, Dedy Hermansyah, Delfitri Munir, Aznan Lelo, Agung Putra, Nur Dina Amalina, Iffan Alif

The Thai Journal of Pharmaceutical Sciences

Breast cancer stem cells (BCSCs) develop apoptosis resistance by expressing pro- and anti-apoptotic protein including caspase-3, p53, and survivin. However, the induction of apoptosis is an important mechanism of action for many anticancer agents. Therefore, treatment using combination therapy was supposed to inhibit apoptosis resistance and increase the possibility of cancer apoptosis. This study aimed to investigate the effects of the combination Curcuma longa (CL) and Phyllanthus niruri (PN) extract on apoptosis induction. The single and combination cytotoxicity was analyzed using MTT assay. Apoptosis was measured by Annexin V-Propidium Iodide under flow cytometry. Caspase 3 expression was assessed by flow …

Synthesis And In Silico Study Of New Azetidinones Against Non-Small Cell Lung Cancer By Egfr Inhibition, Jainey P. James, T. C. Aiswarya, Swetha P. Shenoy, Vinod Devaraji

The Thai Journal of Pharmaceutical Sciences

Background: Lung cancer is alarmingly increasing and therapies targeting receptors such as human epidermal growth factor have been found to be emerging in treating lung cancer. Many studies report azetidinone bearing compounds to be cytotoxic. This work aims to prove the anti-lung cancer action of synthesized azetidinones that are through epidermal growth factor receptor (EGFR) inhibition. Materials and Methods: Novel azetidinone derivatives were synthesized from Schiff bases; molecular docking analyzed the interactions with EGFR, and pharmacophore modeling revealed the features responsible for the possible interactions. Moreover, the compounds with good docking scores were selected for anti-lung cancer study by MTT …

Insights Into Novel Therapeutic Targets And Molecular Aspects In Polycystic Ovarian Syndrome: A Review, Rukaiah Fatma Begum, M. Sumithra, V. Chitra, Sharmila Devi

The Thai Journal of Pharmaceutical Sciences

Polycystic ovarian syndrome (PCOS) is a common endocrine syndrome in women associated with many other complications such as insulin resistance, obesity, hirsutism, increased risk of cardiovascular diseases, and infertility. As the pathophysiology of the syndrome still is not clear, it is difficult for the health-care professionals to precisely treat the syndrome. The cause of this syndrome is also unknown, but the evidences suggest that the factors such as environment, diet, and lifestyle are also a very common cause now a day for the syndrome. Recent pathophysiology of PCOS based on the Anti-Mullerian Hormone (AMH) and melatonin levels has been seen …

Efficacy Of Investigative Candidate Drugs Against Sars Cov-2: An Update On Pre-Clinical And Clinical Trials, Maryam Bibi, Aatika Sadia, Muhammad Shahzad, Ahmad Irfan, Muhammad Asim Raza Basra

The Thai Journal of Pharmaceutical Sciences

The unprecedented challenges presented by COVID-19 pandemic demands for an urgent development of effective therapeutic strategies against the deadly virus. Researchers thus far have revealed outcomes of pre-clinical and clinical studies of different interventions. This study aims to present overall summary of therapeutics that until this date are reported for their efficacy against COVID-19 in pre-clinical and clinical trials. A thorough literature search was conducted using databases for identification of studies published on the severe acute respiratory syndrome CoV (SARS COV-2) treatment. According to pre-clinical experiments, Nefamostat mesylate, Remdesivir, Chloroquine (CQ), Hydroxychloroquine (HCQ), β-D-N4-hydroxycytidine (NHC EIDD-1931), Ivermectin, Boceprevir, Calpain inhibitors, …

Carbon Dots: An Updated Overview On Their Synthesis, Properties, And Applications In Pharmaceutical And Biomedical Sciences, Earle Radha Rani, Majji Usharani, A. Lakshmi Usha

The Thai Journal of Pharmaceutical Sciences

Nowadays, carbon-based materials have acquired more attention in numerous fields including engineering, medicine, and pharmaceutics. As a new class of small carbon nanomaterials, carbon dots are developed due to their excellent physicochemical properties such as spherical shape, non-toxicity, cost effectiveness, facile, biocompatibility, and discrete particles <10 nm in diameter. In 2004, these carbon dots were first discovered accidentally during processing of single walled carbon nanotubes. Carbon dots have created huge excitement due to their advantages such as high water solubility, excellent biocompatibility, and resistance to photo bleaching. Carbon dots show unique properties such as photo stability, low toxicity, fluorescence, photo chemiluminescence, and electrochemiluminescence. Due to these properties, they have a wide range of applications in the field of bioimaging and drug delivery. Carbon dots are classified into two groups: Amorphous based carbon dots and graphene-based quantum dots with sp2 hybridization. The synthesis methods of carbon dots were reviewed along with their advantages and disadvantages. The applications of carbon dots in drug delivery, gene delivery, targeted drug delivery, crossing blood–brain barrier, and bio imaging were discussed.

Antioxidant And Nephroprotective Effects Of Delphinium Denudatum Root Extract (Medicinal Plant) Against Gentamicin-Induced Nephrotoxicity, Nadeem Ahmad Siddique

The Thai Journal of Pharmaceutical Sciences

Introduction and Objectives: Kidney is a front line organ exposed to the toxicity of gentamicin. The objective of this study was to determine the biopotential of Delphinium denudatum Wall., root a significant medicinal plant, against gentamicin. Materials and Methods: By performing high-performance liquid chromatography, an in vitro antioxidant study was conducted against diphenylpicrylhydrazide (DPPH). In vivo nephroprotective activity was evaluated by administering solo administration of gentamicin (GM; 40 mg/kg b.wt. single dose s.c.) for a period of 1st–13th days followed by hydroalcoholic extract of D. denudatum (HAEDD; 200, 400, and 800 mg/kg b.wt. intragastrically) to the rats for 14th–23rd days. …

Alcl3 Induced Neuroinflammation And Excitotoxicity In Brain Striatum Mediated Memory And Motor Dysfunction Ameliorated Via Scopoletin Enriched Canscora Decussata Extract, A. Roja, T. Ambiga, Abdul Khayum, Sulaiman Mohammed, Venkatesh Gunasekaran

The Thai Journal of Pharmaceutical Sciences

Objective: Scopoletin is one of the dynamic and active constituents originate in Canscora decussata (CD) herb from Shankhpushpi family according to Indian system of medicine. This study aimed to characterize and to explore the role of scopoletin enriched CD (SECD) extract on AlCl3-induced neuroinflammation and excitotoxicity in rat model. Methodology & Results: High-performance thin-layer chromatography finger printing of ethanol extract of CD confirmed that enriched scopoletin presence as its main constituent. AlCl3 induced behavioural changes were reversed after SECD (200 and 400 mg/kg, i. p) and Rivastigmine (0.3 mg/kg, i.p) treatment by the way of Y maze, Rota rod, and …

Antidiabetic Study And Teratogenicity Evaluation Of Ethanolic Extract Of Chromolaena Odorata Linn., Indah Solihah, Yuni Fitriani, Meutia Reni Noprida, Herlina, Riana Sari Puspita Rasyid, Tri Suciati

The Thai Journal of Pharmaceutical Sciences

There is considerable interest in herbal medicine in developing antidiabetic alternative therapy based on plant-derived compounds that would reduce oral hypoglycemic agent-related adverse effects while staying safe during pregnancy. The purpose of this in vivo study was to evaluate the ethanolic extract of Chromolaena odorata L. leaves (ECOL) in alloxan-induced diabetes and its teratogenic effect. The hypoglycemic impact of ECOL increased when the extract dose was raised. Three doses of ECOL (125, 250, and 500 mg/kg body weight) showed a 27.29%, 34.68%, and 52.24% hypoglycemic effect, respectively. While, the standard insulin (1 IU/kg BW) group shown a 31.38% hypoglycemic effect …

Anti-Diabetic Effect Of Interruptins A And B From Cyclosorus Terminans On Mouse Hepatocytes, Sujinda Songtrai, Sireewan Kaewsuwan

The Thai Journal of Pharmaceutical Sciences

Interruptin B from the fern Cyclosorus terminans has been indicated as a ligand of peroxisome proliferator-activated receptor (PPAR)-α and -γ that is known to regulate glucose homeostasis. Interruptin B was previously been implicated to promote glucose consumption into adipocytes. This study aimed to examine the anti-diabetic impact of interruptins A and B on glucose uptake and glycogen synthesis in mouse hepatocytes. Cell viability of FL83B hepatocytes affected by interruptins A and B was determined. The glucose consumption after 12–24 h treatment with compounds was evaluated by glucose oxidase method. The glycogen content was assessed after 24 h incubation using anthrone …

Assessment Of Risk Factors And Prescription Analysis Among Embolic And Atherosclerotic Stroke Patients In A Charitable Hospital-A Retrospective Study, Shanty Mary Jose, Amala Johnson, Akshay Abraham, Uday Venkat Mateti, Adithi Kellarai, Raushan Kumar Chaudhary, Shraddha Shetty

The Thai Journal of Pharmaceutical Sciences

Purpose: Despite the burden of stroke globally, there is a lack of data on the current clinical profile of stroke in middle and low-income countries including, India. Hence, the purpose of this study was to identify risk factors, clinical presentations, and importantly, prescription trends in ischemic stroke patients. Methods: A retrospective study was conducted for six months using data of 350 ischemic stroke patients for the analysis of risk factors and prescription pattern. Results: The incidence of ischemic stroke was higher (66%) in males in compared to (34%) females with mean age of 61.07 ± 11.460. Further the atherosclerotic stroke …

Effect Of Hyperoxia On Cardiac Pathophysiology In Female Guinea Pig Hearts, Chayapatou Chayawatto

USF Tampa Graduate Theses and Dissertations

Hyperoxia is widely implemented in critical care and ICU patients. The administration of a high concentration of inspired oxygen to the lung can unknowingly cause hyperoxia and thereby damaging the lungs and heart due to oxidative stress. Technically, hyperoxia occurs when the patient receives PaO2 > 200 mmHg. Major research focused on hyperoxia-induced lung injury, but nothing is known on its effect on heart. Our lab is the pioneer in understanding the effect of hyperoxia on cardiovascular remodeling using mice model. Previous results show that mice under 72 hours of hyperoxia present severe cardiac pathophysiology. This research uses Guinea pigs, which …

Poststroke Seizure And Epilepsy: A Review Of Incidence, Risk Factors, Diagnosis, Pathophysiology, And Pharmacological Therapies, Joseph Phan, Mario Ramos, Theodore Soares, Mayur S. Parmar

HPD Articles

Stroke is the most common cause of epilepsy and ultimately leads to a decrease in the quality of life of those affected. Ischemic and hemorrhagic strokes can both lead to poststroke epilepsy (PSE). Significant risk factors for PSE include age less than 65 years, stroke severity measured by the National Institutes of Health Stroke Scale (NIHSS), cortical involvement, and genetic factors such as TRPM6 polymorphism. The diagnosis of PSE is made by using imaging modalities, blood biomarkers, and prognostic criteria. Electroencephalography (EEG) is currently the gold standard to diagnose PSE, while new combinations of modalities are being tested to increase …

Association Between Use Of Remdesivir And Bradycardia, Gibret Umeukeje

USF Tampa Graduate Theses and Dissertations

Remdesivir received the first emergency use authorization from the FDA for the treatment of COVID-19. Multiple adverse drug reactions (ADR) have been reported since its approval in October 2020. Bradycardia, defined by a decrease in heart rate has been reported as an adverse event for patients receiving remdesivir for COVID-19 treatment. The purpose of the research is to systematically investigate the frequency of occurrence of bradycardia in adults receiving remdesivir using clinical data derived from the FDA Adverse Event Reporting System (FAERS) database. Patients receiving remdesivir were compared to those receiving Paxlovid, Regen-Cov, and Dexamethasone for COVID-19 treatment to see …

Screening Pathological Protein Specific Antibodies As Biomarker Discovery Tools For Neurodegenerative Disease, Yitong Li

USF Tampa Graduate Theses and Dissertations

With the increase in the average life span, the incidence of neurodegenerative diseases also increases, among which Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common types of neurological disorders. AD and PD share the same pathogenic mechanism that involves a class of proteins called beta-amyloid (Aβ), which, under the induction of some factors, changes from its natural monomeric state to the oligomers containing β-sheet, which is neurotoxic and thus leads to cell damage or apoptosis. This study focused on the selection of antibodies used as biomarkers for AD and PD. The selection of antibodies was based …

Interactions Between Environmental Factors And Glutathione S-Transferase (Gst) Genes With Respect To Detectable Blood Aluminum Concentrations In Jamaican Children, Mohammad H Rahbar, Maureen Samms-Vaughan, Yuansong Zhao, Sepideh Saroukhani, Jan Bressler, Manouchehr Hessabi, Megan L Grove, Sydonnie Shakespeare-Pellington, Katherine A Loveland

Faculty, Staff and Student Publications

Aluminum (Al) is a metallic toxicant at high concentrations following natural or unnatural exposures. Dietary intake is considered as the main source of aluminum exposure in children. We used data from 366 typically developing (TD) children (ages 2−8 years) who participated as controls in an age- and sex-matched case−control study in Jamaica. We investigated additive and interactive associations among environmental factors and children’s genotypes for glutathione S-transferase (GST) genes (GSTT1, GSTM1, GSTP1), in relation to having a detectable blood aluminum concentration (BAlC) of >5.0 μg/L, using multivariable logistic regression models. Findings from interactive models revealed that the odds of having …

A Trichy Situation, Kathryn Purple

Cumberland Mountain Naturalist

This issue of the Cumberland Mountain Naturalist discusses Dr Kathryn Purple's research concerning Trichomonosis carried by pigeons.

Response Of Soil Bacterial Diversity, Predicted Functions And Co-Occurrence Patterns To Nanoceria And Ionic Cerium Exposure, Jie Zhang, Hui Sheng, Yan-Meng Shang, Jamie Lead, Zhang-Zhen Guo, Jian-Ping Hong

Faculty Publications

Release of nanoceria (nCeO₂) into the environment has caused much concern about its potential toxicity, which still remains poorly understood for soil microorganisms. In this study, nanoceria and cerium (III) nitrate at different doses (10, 100 and 500 mg/kg) were applied to bok choy (Brassica rapa subsp. chinensis), grown in potting soil, to investigate the responses of soil bacterial communities to nanoceria (NC) and ionic cerium (IC) applications. The results showed that bacterial richness was slightly increased in all cerium treatments relative to the negative control without cerium amendment (CK), but a significant increase was only found in …