Pharmacology Commons^™

Selective Gsk3b Overexpression In Medial Prefrontal Cortex Camkiia Cells Produces Sex-Specific Changes In Ethanol Self-Administration, Anxiety-Like Behavior, And Working Memory, Sam Gottlieb, Zachary Tatom, Michael F. Miles

Graduate Research Posters

Background: Glycogen synthase kinase 3 beta (Gsk3b) is central in a gene network regulated by ethanol in mouse medial prefrontal cortex (mPFC). GSK3B abundance/activity modulations regulate ethanol consumption, suggesting GSK3B could be a target in treating alcohol use disorder. However, the critical cell type in this ethanol response is not yet known, nor have sex differences in GSK3B modulations been fully investigated. Here we report results of GSK3B overexpression selectively in CamKIIa⁺ mPFC cells on multiple behaviors.

Methods: Mice underwent stereotaxic injections to overexpress GSK3B in mPFC CamKIIa⁺ cells or control virus (n=4-6/sex/virus). We assayed working …

Nutritional & Colorectal Health, Tariq A. Alam, Brittany R. Rice, Sara B. Police

Journal of Pharmacology & Nutritional Sciences

Kentucky has the highest incidence and mortality rate of all site cancers, and Kentuckians residing in the Appalachian region often have worse outcomes, where cancer is a leading cause of death. Focusing on colorectal cancer (CRC) specifically, Kentucky ranks first nationwide for incidence (50 cases per 100,000 people) and fifth for mortality (about 17 deaths per 100,000 people). The Kentucky Colon Cancer Screening Program increased screening rates and reduced mortality since its launch. Yet, CRC remains a leading cause of death for Kentuckians. Risk factors for CRC include increasing age as well as a history of inflammatory bowel disease (IBD) …

Modulation Of Opioid-Induced Respiratory Depression By Stimulants And Their Associated Monoaminergic Receptor Mechanisms In Mice Using Whole Body Plethysmography, Harrison J. Elder

Theses and Dissertations

Opioid overdose and associated deaths involving opioid-induced respiratory depression (OIRD) began to accelerate beginning in 2015 with the emergence of illicitly manufactured fentanyl and its analogs and currently represents one of the most significant public health challenges in the United States. The increases in overdose deaths have occurred despite the increased availability of the opioid overdose reversal agent, naloxone, to first responders and the public. This new phase of the opioid epidemic has been paralleled by substantial growth in the co-use of opioids with stimulants, particularly methamphetamine. The objective of this dissertation is to ascertain whether fentanyl is particularly resistant …

Novel Strategies In Head And Neck Tumor Therapy; Contribution Of Senescence In Therapy Response, And Resistance Development After Cisplatin Treatment, Fereshteh Ahmadinejad

Theses and Dissertations

Therapeutic outcomes achieved in head and neck squamous cell carcinoma (HNSCC) patients by concurrent cisplatin-based chemoradiotherapy initially reflect both tumor regression and tumor stasis. However, local, and distant metastasis and disease relapse as well as cisplatin-induced resistance are common in HNSCC patients. In the current work, we demonstrate that cisplatin treatment induces senescence in both p53 wild- type HN30 and p53 mutant HN12 head and neck cancer models. We also show that tumor cells can escape from senescence both in vitro and in vivo. We further established a cisplatin-resistant cell line from HN30 parental cell line that underwent brief senescence …

Effectiveness Of A Long-Acting Cocaine Hydrolase In Metabolizing Cocaine And Its Physiologically Active Metabolites, Linyue Shang

Theses and Dissertations--Pharmacy

Cocaine is a widely abused, hepatotoxic drug without an FDA-approved pharmacotherapy specific for cocaine addiction or overdose. Cocaine-induced toxicity in animals and humans is due to its multiple physiological effects on the central nervous system, cardiovascular system, etc. The toxicity of cocaine is highly complex, as its metabolites also contribute to the toxicity. Notably, the combination of cocaine and alcohol is common among drug users and can produce additional metabolites. Some of the metabolites are more toxic than cocaine itself. Hence, to develop an ideal therapeutic candidate, the candidate should not only account for cocaine but should also detoxify other …

Age-Associated Increase Of Gamma Delta T Cells In Visceral Adipose Tissue And Mechanisms Of Their Accumulation, Sujata Mukherjee

Theses and Dissertations--Pharmacology and Nutritional Sciences

Chronic systemic inflammation, known as inflammaging is considered a hallmark of aging and associated diseases. While adipose tissue has long been considered only as a caloric reservoir regulating systemic energy homeostasis, research in the past couple of decades substantiate its endocrine function to secrete an array of inflammatory mediators and hormones, which have physiological effects on multiple organ systems, and contribute to inflammaging. Redistribution of adipose tissue from subcutaneous to visceral depots, changes in the immune profile and the chronic inflammatory state are among the major sources of adipose tissue dysfunction with aging.

This dissertation is focused on identifying and …

Chemical Immobilization Of Helicopter-Captured Elk (Cervus Canadensis) And Survival Of Elk Calves In Southeastern Kentucky, Kathleen E. Williams

Theses and Dissertations--Forestry and Natural Resources

Safe and effective chemical immobilization is critical to minimize stress and risk of injury when capturing free-ranging, wild ungulates. Many traditionally favored high potency opioids have been phased out or become unavailable because of increased regulations, leading to the development of two pre-mixed combination drugs, butorphanol-azaperone-medetomidine (BAM) and nalbuphine-medetomidine-azaperone (NalMed-A). Both drugs have been used to chemically immobilize ungulates, but their efficacy has not been documented in elk captured and transported via helicopter. During 2020 – 2022, we chemically immobilized helicopter-captured female elk (Cervus canadensis) with a single IM-injection of BAM (n = 41) or NalMed-A (n = …

Alternative Pharmacology: Exploring Ketamine Use For Treatment Resistant Mental Health Disorders, Kiersten L. Ash

Soaring: A Journal of Undergraduate Research

No abstract provided.

Covid-19 Vaccination And Alcohol Consumption: Justification Of Risks, Pavel A. Solopov

Bioelectrics Publications

Since the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, pharmaceutical companies and research institutions have been actively working to develop vaccines, and the mass roll-out of vaccinations against COVID-19 began in January 2021. At the same time, during lockdowns, the consumption of alcoholic beverages increased. During the peak of vaccination, consumption remained at high levels around the world, despite the gradual relaxation of quarantine restrictions. Two of the popular queries on search engines were whether it is safe to drink alcohol after vaccination and whether this will affect the effectiveness of vaccines. Over the past two …

Mitoq Alleviates Hippocampal Damage After Cerebral Ischemia: The Potential Role Of Sirt6 In Regulating Mitochondrial Dysfunction And Neuroinflammation, Ayman A. Ibrahim, Sherif S. Abdel Mageed Dr, Marwa M. Safar Prof.Dr, Mohammed F. El-Yamany Prof.Dr., Mamdouh A. Oraby Dr.

Pharmacy

Aims: Mitochondrial perturbations are the major culprit of the inflammatory response during the initial phase of cerebral ischemia. The present study explored the neuroprotective effect of the mitochondrial-targeted antioxidant, Mitoquinol (MitoQ), against hippocampal neuronal loss in an experimental model of brain ischemia/ reperfusion (I/R) injury. Main methods: Rats were subjected to common carotid artery occlusion for 45 min, followed by reperfusion for 24 h. MitoQ (2 mg/kg; i.p daily) was administered for 7 successive days prior to the induction of brain ischemia. Key findings: I/R rats exhibited hippocampal damage evidenced by aggravated mitochondrial oxidative stress, thereby enhancing mtROS and oxidized …

Developmental Pharmacokinetics Of Indomethacin In Preterm Neonates: Severely Decreased Drug Clearance In The First Week Of Life., Wojciech Krzyzanski, Bradley Stockard, Andrea Gaedigk, Allison Scott, Whitney M. Nolte, Kim T. Gibson, J Steven Leeder, Tamorah Lewis

Manuscripts, Articles, Book Chapters and Other Papers

Indomethacin is used commonly in preterm neonates for the prevention of intracranial hemorrhage and closure of an abnormally open cardiac vessel. Due to biomedical advances, the infants who receive this drug in the neonatal intensive care unit setting have become younger, smaller, and less mature (more preterm) at the time of treatment. To develop a pharmacokinetics (PK) model to aid future dosing, we designed a prospective cohort study to characterize indomethacin PK in a dynamically changing patient population. A population PK base model was created using NONMEM, and a covariate model was developed in a primary development cohort and subsequently …

Preclinical Study On Hepatoprotective Potential And Antioxidant Status Analysis Of The Fruit Extract Of Rivina Humilis L. (Red Pigeon Berry) In Rats, Raju Asirvatham, Dinu George, P. A. Daisy, Dawn V. Tomy, G. Boby Johns

The Thai Journal of Pharmaceutical Sciences

Hepatoprotective and antioxidant potential of hydromethanolic extract of Rivina humilis L. fruit (HMERH) was studied using the carbon tetrachloride (CCl4) and paracetamol (PCM) induced hepatotoxicity in Wistar rats. In both models, rats were divided into five groups having six rats in each. Group I received distilled water. Group II, disease control, Group III received 100 mg/kg of Silymarin. Group IV and Group V received 500, 1000 mg/kg of HMERH. All groups except Group II received treatment twice daily for 7 days. CCl4 (1.5 mL/kg, PCM (2 g/kg), p.o) were administered after the last dose. The degree of liver protection against …

Development Of A Thai Pharmacists’ Cultural Competency Self-Assessment Scale, Auttakrit Aunkaew, Puckwipa Suwannaprom, Siritree Suttajit

The Thai Journal of Pharmaceutical Sciences

Objective: The objective of the study was to develop and evaluate a cultural competency assessment form for Thai pharmacists. Materials and Methods: The research was conducted in two phases. Phase 1 involved item development based on the Campinha-Bacote’s and the ACPP’s concept of cultural competency and the self-assessment of perceived level of cultural competence questionnaire. Seven experts assessed the content validity and face validity. The revised scale was tested for comprehension among 12 pharmacists using the think-aloud technique. Phase 2 constituted the scale development and scale evaluation. The Thai pharmacist cultural competency self-assessment (TPCCS) scale developed from Phase I was …

Pharmacological Evaluation Of The Antirheumatic Activity Of Callicarpa Macrophylla Leaves Extracts By The Estimation Of Hepatic, Renal, And Inflammatory Markers, Harjinder Kaur, Ganesh N. Sharma, Mayur Bhurat

The Thai Journal of Pharmaceutical Sciences

Background: Callicarpa macrophylla is used in traditional medicine to treat many disorders including analgesic, antipyretic and anti-inflammatory. The aim of this study is to investigate the ethanolic and ethylacetate extracts of C. macrophylla leaves against rheumatoid arthritis (RA). Materials and Methods: Acute toxicity was studied in vivo to determine the toxic doses of the ethanolic and ethyl acetate extracts. Anti-rheumatic activity was also evaluated in vivo using formaldehyde and Complete Freund’s Adjuvant models in Wistar rats. After that paw volume was evaluated by the digital Vernier caliper and blood sample was taken by retro-orbital plexus route for the estimation of …

Ascorbic Acid-Loaded Poly(Lactic-Co-Glycolic Acid) Nanoparticles Incorporated Into A Polyacrylic Acid Gel As A Promising Tool For Site-Specific Oral Cancer Therapy, Nurul Ain Mohammad Hamdi, Ahmad Fahmi Harun Ismail, Muhammad Salahuddin, Widya Lestari

The Thai Journal of Pharmaceutical Sciences

Background: Chemotherapy is commonly used in oral cancer therapy, especially as the disease advances. However, it is associated with terrible adverse effects and the occurrence of chemoresistance which causes treatment failure. Thus, discovering a new potential anticancer agent and developing a safe, effective, and non-invasive drug delivery are necessary. Objective: The objective of the current study is to develop ascorbic acid-loaded poly(lactic-co-glycolic) acid (AA-PLGA) nanoparticles incorporated into polyacrylic acid gel intended to treat oral cancer. Materials and methods: Double emulsion solvent evaporation method was used to fabricate AA-PLGA nanoparticles. Optimization was carried out in the primary emulsion based on multilevel …

Vegetable Oil-Based Cannabis: Its Cannabinoid Profiling And Photoprotective Effect On Uva-Irradiated Human Skin Keratinocytes, Nur Alfan Muhammad Zen, Kwanlada Kobtrakul, Petlada Khositanon, Kittipong Sanookpan, Visarut Buranasudja, Sornkanok Vimolmangkang

The Thai Journal of Pharmaceutical Sciences

Vegetable oils serve as affordable, non-toxic, and eco-friendly solvents for plant extraction. Chemical fingerprinting shows that vegetable oil-based cannabis has a cannabinoid profile similar to that of organic solvent-based cannabis. All samples possess antioxidative effects as they contain several cannabinoids and other unidentified compounds, with rice bran oil-based sample exhibiting the strongest effect. Tetrahydrocannabinol (THC) and cannabidiol (CBD) content in sesame oil-based and perilla seed oil-based cannabis differed significantly from that in virgin coconut oil (VCO)-based cannabis. In addition, THC and CBD content in all vegetable oil-based samples prepared using the heating and frying method differed significantly from that in …

Clinical Vaccination Education Guideline For The African American Community, Margaret Chinedum Nwoji

Walden Dissertations and Doctoral Studies

AbstractVaccination hesitancy is high among African Americans and other people of color. The practice gap addressed in this project was the lack of a culturally sensitive clinical guideline for vaccination education relevant to the African American community. The practice-focused question was answered by developing an evidence-based Clinical Vaccination Education Guideline for the African American Community (CVEGAAC) that was validated by a group of four content experts using the Appraisal of Guidelines, Research, and Evaluation tool. The content experts scored each of the domains above 90%, implying that the CVEGAAC is of high quality and ready for implementation. The end users …

Xylazine Suppresses Fentanyl Consumption During Self-Administration And Induces A Unique Sex-Specific Withdrawal Syndrome That Is Not Altered By Naloxone In Rats, Shailesh N. Khatri, Safiyah M. Sadek, Percell T. Kendrick, Emma O. Bondy, Mei Hong, Sally Pauss, Dan Luo, Thomas E. Prisinzano, Kelly E. Dunn, Julie A. Marusich, Joshua S. Beckmann, Terry D. Hinds Jr., Cassandra D. Gipson

Markey Cancer Center Faculty Publications

Prescription and illicit opioid use are a public health crisis, with the landscape shifting to fentanyl use. Since fentanyl is 100-fold more potent than morphine, its use is associated with a higher risk of fatal overdose that can be remediated through naloxone (Narcan) administration. However, recent reports indicate that xylazine, an anesthetic, is increasingly detected in accidental fentanyl overdose deaths. Anecdotal reports suggest that xylazine may prolong the fentanyl “high,” alter the onset of fentanyl withdrawal, and increase resistance to naloxone-induced reversal of overdose. To date, no preclinical studies have evaluated the impacts of xylazine on fentanyl self-administration (SA; 2.5 …

Intrinsic Efficacy As A Determinant Of Opioid Effectiveness In Treatment Of Pain-Depressed Behavior, Edna Santos

Theses and Dissertations

Pain is a major public health concern that is commonly associated with behavioral depression, and a major goal in pain treatment is alleviation of pain-related behavioral depression. High-efficacy mu opioid receptor (MOR) agonists (e.g. fentanyl, morphine, oxycodone) are effective to treat pain, but their use is limited by side effects that not only endanger the patient but may also obscure analgesic rescue of pain-depressed behavior. The ongoing epidemic of opioid abuse and overdose deaths has stimulated research to discover non-opioid alternative analgesics; however, this search neglects the clinical potential of safer intermediate-efficacy MOR agonists (e.g. buprenorphine). The objective of the …

The Impact Of Hiv-1 Tat And Morphine On Spatial Distribution Of Drugs In The Brain., Austin M. Jones

Theses and Dissertations

Despite combination antiretroviral therapy effectively suppressing HIV within the periphery, the central nervous system (CNS) remains affected by the virus. Approximately half of people living with HIV will experience HIV-associated neurocognitive disorders (HAND) or neuroHIV. Concurrent opioid use exacerbates neuroHIV by promoting neuroinflammation, viral replication, and potentially altering the antiretroviral concentrations within the brain.

Using a transgenic mouse that expresses the HIV-1 Tat protein, we examined the effects of Tat and morphine on antiretroviral accumulation and distribution and the effects of Tat on morphine accumulation within the brain using infrared matrix-assisted laser desorption electrospray ionization with mass spectrometry imaging (IR-MALDESI-MSI). …