Pharmacology Commons^™

Oxidative Potential And Composition Of Fine Particulate Matter At Two Locations In Mississippi, Victoria Claire Stevens

Honors Theses

Air pollution exposure has negative health effects on individuals across the globe. Negative impacts on human health have been documented in studies following both short-term and long-term exposure to air pollution, and these adverse effects have been seen even at the lowest levels of exposure. Fine particulate matter (PM_2.5) has specifically been linked to these negative health effects. These effects come from many sources, but one large contribution to the negative health effects comes from oxidative stress. In this study, samples were collected from Hernando, MS and Gulfport, MS in September 2013 and November 2013. Black carbon (BC) …

Hiv-1 Tat Interactions With Opioids Are Modulated By Progesterone And Estradiol, Dejun Jackson

Honors Theses

HIV infection and combined substance abuse are comorbid epidemics. Previous studies show that concurrent opioid drug use may potentiate HIV-1-mediated neurotoxicity partly via interactions with opioids. Preclinical studies suggest that the HIV-1 trans-activator of transcription (Tat), an HIV regulatory protein, can synergize with opioids to exacerbate its already neurotoxic effects. However, its interactions with clinical opioids, such as oxycodone, have yet to be elucidated. Additionally, Tat disrupts a number of systems including the dopaminergic system, which contribute to its capacity to potentiate the rewarding effects of abused drugs. Although the neurotoxic effects of Tat may be inhibited by gonadal steroids …

The Impact Of Age/Rage Signaling On Oxidative Stress Under Diabetic Conditions In Cardiac Fibroblasts, Christopher Dorroh

Honors Theses

Diabetes is a major health concern in the United States, with 1.5 million new cases diagnosed each year. Patients who suffer from diabetes have an increased risk of developing heart failure, a form of cardiovascular disease. Heart failure has been shown to result from increased left ventricular stiffness, which in turn is caused by increased remodeling of the extracellular matrix (ECM). This increase in ECM remodeling is a result of AGE/RAGE signaling, which occurs at a heightened level in the cardiac fibroblast cells of diabetics. Studies have shown that diabetics have elevated levels of AGEs (Advanced Glycation End-Products), which bind …

Impacts Of Embryonic Exposure To Cannabidiol Or ∆9-Tetrahydrocannabinol On Zebrafish (Danio Rerio) Frailty In F0 And F1 Generations, Anika Faruque

Honors Theses

Exposure to cannabinoids during critical development periods has increased with epileptic children being commonly prescribed CBD for seizures and pregnant women taking it recreationally. Many studies have been done on the possible benefits and drawbacks of cannabinoid exposure on the human brain, but not much is known about how it can affect the developing brain long-term. To see the potential adverse effects of cannabinoid exposure during critical stages of development and discover potential developmental origins of disease in consuming cannabinoids during embryogenesis, zebrafish embryos (6-96 hours post fertilization) were exposed to varying concentrations of CBD (0.02, 0.1, 0.5 µM), THC …

Development Of Inhalable Nano-Lipid Carriers For The Treatment Of Pulmonary Aspergillosis Using Hot Melt Extrusion Technology, Gauri Shadambikar

Graduate Student Council Research Grants

Overview: I am Gauri Shadambikar, second year PhD. student in department of Pharmaceutics and Drug Delivery. Pulmonary Aspergillosis is an infection caused by a type of mold and can have serious effects on patients with a weak immune system or with underlying lung disease1. Itraconazole, a triazole is a compound with a broad antifungal spectrum. 2. An inhalation-based drug delivery system has the advantage of rapid onset of action directly at the site of infection along with controlled and prolonged delivery. 3. Hence the aim of my project was to prepare inhalable nano-lipid carriers (NLC) which would be a viable …

Assessment Of Underlying Neurocircuitry In Dysregulation Of The Hypothalamic Pituitary Adrenal Stress Axis In Hiv-1 Tat Male Mice, Salahuddin Mohammed

Graduate Student Council Research Grants

Overview: My name is Salahuddin Mohammed, a 2nd year PhD graduate student from Dr. Jason Paris’ Lab. My research dissertation focuses on investigating the neuroendocrine underpinnings of HIV-and opioid-mediated anxiety-/depression-like behavior and cognitive impairment via experiments utilizing humans and animal models. Through this work I strive to delineate the underlying mechanism for the neuroHIV symptomology and develop novel therapeutic agents which can ameliorate HIV-1 mediated Tat-neurotoxicity. Approximately 50% of the HIV infected patients suffer from HIV associated neurocognitive disorders (HAND) which can be exacerbated by drug use/abuse. Some neuroHIV symptoms include anxiety, major depressive disorder, neurocognitive impairment, and additional psychiatric …

Development Of Itraconazole Topical Formulation In Skin Cancer Treatment, Praveen Kolimi

Graduate Student Council Research Grants

Overview: I, Praveen Kolimi, pursuing a first-year graduate program at the department of pharmaceutics and drug delivery. This Graduate Student Council (GSC) grant proposal focus on topical application of Itraconazole (ICZ) in skin cancer treatment.

Intellectual Merit: 5.4 million skin cancer cases are reported each year in the United States. A study disclosed that one among five Americans are likely to develop skin cancer in their entire life. 9. Skin cancer can be distinguished into two types, malignant melanoma (MM) and non-melanoma skin cancer (NMSC) 1, 8. NMSC further classified into squamous cell carcinoma (SCC) and basal cell carcinoma (BCC)8, …

The Role Of Insulin-Like Growth Factor 1 In Specific Brain Cells Following Ischemia, Cellas Hayes

Graduate Student Council Research Grants

Overview: My name is Cellas Ari’ka Hayes, and I am a first-year graduate student in the School of Pharmacy Department of BioMolecular Sciences. I am pursuing a Ph.D. in Pharmaceutical Sciences with an emphasis in Pharmacology. My project will assess the effects of insulin-like growth factor-1(IGF-1), an anabolic polypeptide on the damage caused by ischemic stroke including glial cell death, neuronal tress, infarct size, neurological deficits, and behavioral changes.

Intellectual Merit: Ischemia is one of the largest causes of neurological deficits that in elderly individuals in the United States [1]. Since our life expectancy has increased concurrently without predispositions to …

Α-Tocopherol Succinate Nanostructured Lipid Carriers For The Ocular Delivery Of The Anti-Neoplastic Agent, Sushrut Marathe

Graduate Student Council Research Grants

Overview: Retinoblastoma (RB) is a rare form of cancer that rapidly develops from the immature cells of the retina, the light-detecting tissue of the eye. The treatment options of RB has been limited to enucleation, external beam radiotherapy, episcleral plaque radiotherapy and cryotherapy. α-Tocopherol succinate(αTS), has been proven to an effective apoptogenic agent. It can enhance the efficiency of the anticancer agent1. Paclitaxel (Ptx) is a potent chemo agent and is widely used in the treatment of various types of cancers. However, clinical use of Paclitaxelis limited by systemic toxicity, rapid clearance and resistance 2,3.The formulation of paclitaxel poses the …

A Mechanistic Study Of The Teratogenic Potential Of 4-O-Methylhonokiol (Mh) On Japanese Medaka (Oryzias Latipes), Santu Kumar Singha

Electronic Theses and Dissertations

An additional goal of this project was to characterize the Wnt/β-catenin signaling pathway to unravel the adverse potential of MH on the cardiovascular system (CVS). Our study suggested that MH-mediated cardiovascular injury may be caused due to upregulation of some major components of the Wnt/β-catenin pathway through expression of excessive pro-inflammatory mediators. Moreover MH decreased expression of ErbB3 and NRG-2 suggesting impaired cardiac structure. MH exposure caused a slow heartbeat blood occlusion absence of blood circulation decreased hatching efficiency and increased mortality in medaka embryos in a concentration- and time-dependent manner. MH might cause blood vessel occlusion by increasing the …

Continuous Production Of Raloxifene Hydrochloride Loaded Nanostructured Lipid Carriers Using Hot-Melt Extrusion Technology, Derick Muhindo

Electronic Theses and Dissertations

The aim of this study was to utilize a continuous process for the production of Raloxifene Hydrochloride (RX-HCl) loaded NLC formulations for extended drug release using hot-melt extrusion technology coupled with probe sonication, and also to evaluate the in vitro characteristics of the prepared NLCs by particle size, PDI, zeta potential, entrapment efficiency, drug loading, and in vitro drug release profile. Preparation of the NLCs using HME technology involved two main steps, first formation of a pre-emulsion after extrusion and then size reduction of the pre-emulsion using probe sonication to obtain the NLCs. Process parameters for the extrusion process like …

Pharmacokinetic Study Of Novel Anthraquinone Analogues, Yuhan Guo

Electronic Theses and Dissertations

Small molecules functioning as negative regulators of MDM2 have been considered as promising anti-cancer agents. A series of novel anthraquinone (AQ) analogues upregulate p53, a well-known tumor suppressor, by inactivating its antagonist protein MDM2. The novel AQ compounds synthesized through the modifications on the rhein scaffold were reported to have successfully arrested tumor growth. To have a better understanding of their underlying metabolism in vivo, pharmacokinetic (PK) studies were performed for the AQ compounds. A selective, accurate and reproducible assay methodology for PK study was set up for each AQ compound. The stabilities of AQ compounds were then evaluated …

Implementing Mass Spectrometry For The Structural And Compositional Analysis Of Proteins, Mohammad Riaz

Electronic Theses and Dissertations

Lectins are sugar-binding proteins that perform various biological functions such as cellular recognition attachments etc. Pulses the dried edible seeds of certain plants are great sources of lectins and a proteomics approach directed at lectins identification would bring substantial improvement in the lectin identification process. Lectins from nine different plant species were analyzed through SDS-PAGE and proteomics analysis. After LC-MS/MS analysis proteins were identified with protein database searches using Uniprot. Functionally uncharacterized proteins were identified with database searches were annotated with the Pfam and NCBI-CCD databases. In-vitro pharmacological screening will be carried out to assess the pharmacological effects of these …

Developing Zebrafish As An In Vivo Model To Screen Compounds For Anti-Cancer Activity In Human Breast Cancer, Trisha Dhawan

Electronic Theses and Dissertations

Breast Cancer (BC) is the most frequently diagnosed cancer; 1:8 women are at risk of developing BC in her lifetime. Cancer metastasis causes the majority of deaths in BC patients. Moreover, side effects of traditional chemotherapeutic drugs (TCD) impair the quality of life of these patients. Discovery and development of safe and effective new therapies is imperative for the treatment of BC and targeting metastasis. The goal herein is to further expand the applicability of in vivo xenotransplantation of human BC cells in transgenic zebrafish to screen potential chemotherapeutics for toxicity and efficacy. For xenotransplantation, MCF-7, BT-474, and MDA-MB-231 BC …

Safety Assessment And Chemical Fingerprint Analysis Of Medicinal Plants Commonly Consumed As Herbal Teas; Rooibos (Aspalathus Linearis) And Moringa (Moringa Oleifera), Omer I. Fantoukh

Electronic Theses and Dissertations

The first chapter discusses the significance of natural products, safety challenges, and quality issues concisely. Specifically, the impact of herb-drug interaction on consumers and the quest for chemical markers for chemical fingerprinting development are provided. Rooibos tea (Aspalathus linearis) is a popular South African herbal tea enjoyed worldwide. Limited reports indicate the potential of rooibos tea to alter the activity of CYP450 isozymes. In chapter two, the phytochemical investigation of A. linearis resulted in the isolation and characterization of 14 phenolic compounds. Safety assessment of the phytochemicals through interaction with CYP, PXR, and P gp was conducted. The …

G-Quadruplexes As Molecular Targets For Transcriptional Control, Rhianna Kyelle Morgan

Electronic Theses and Dissertations

DNA G-quadruplexes (G4s) have gained interest in modern drug discovery efforts. The majority of G4 research, including the mass of this research, heavily focuses on cancer therapeutic development, as G4s are more pronounced in oncogenic promoters compared to the rest of the genome, our efforts extend towards neuroprotection as well. In particular, this work covers G4s in the promoters of MYC, VEGF, kRAS, and Bcl-2. MYC and VEGF harbor the two most well described promoter G4s to date, and their stabilization cultivates transcriptional silencing. Downregulation of MYC reduces cell growth and alters cell energetics; it is promising for a variety …

The Efficacy Of Prostaglandin Synthase Inhibition On Attenuating Pressure Overload Induced Cardiac Remodeling, Krishna T. Nagalla

Electronic Theses and Dissertations

Chronic hypertension has long been known to cause left ventricular remodeling. Although previous studies pointed towards inflammation as the pathological driver of cardiac remodeling, the exact mechanistic pathway associated with pressure overload-induced cardiac remodeling remains to be elucidated. In order to address this issue, we designed this study to determine pathways associated with pressure overload induced cardiac remodeling and identify therapeutic targets to attenuate this maladaptive cardiac remodeling. Rats with surgically constricted abdominal aorta were used as an animal model for pressure overload and associated Left ventricular (LV) structure and functional changes were measured by pressure-volume admittance catheterization. Human cardiac …

Perspectives On Ethanol Toxicity In Medaka Embryogenesis And Possible Protection By Asian Ginseng (Panax Ginseng): Histological And Biochemical Analysis, Mona Hamdi Haron

Electronic Theses and Dissertations

Alcohol is recognized as a classic teratogen capable of inducing a wide range of developmental abnormalities. Alcohol consumption during pregnancy may produce permanent brain damage in the fetus and is associated with the development of a life-long behavioral, social, and cognitive disorder now known as fetal alcohol spectrum disorder (FASD). The most clinically recognizable form of FASD is fetal alcohol syndrome (FAS) which is characterized by specific features including facial dysmorphogenesis, mental dysfunction, growth retardation, and cardiovascular and limb defects. Due to ethical constraints, human studies of FASD are very limited. Therefore our current understanding of FASD is mainly based …

Valproic Acid-Induced Teratogenesis In Japanese Rice Fish (Oryzias Latipes) Embryogenesis, Mengmeng Wu

Electronic Theses and Dissertations

Valproic acid (VPA) was introduced as an antiepileptic in 1967 in France and it has become the most prescribed anticonvulsive drug therapy worldwide since then. In the clinic, valproic acid is selected to treat absence seizures, myoclonic seizures, generalized tonic-clonic seizures, atonic attacks and partial seizures. Epilepsy is the second most comneurologic disorder that affects pregnant women (0.5%–1%). Approximately 1 out of 250 pregnant women are taking antiepileptic drugs. Valproic acid is designated as a human teratogen, which induces major congenital anomalies, facial dysmorphic features, and autistic-like behaviors, which affect verbal, cognitive, communicative, and social abilities of affected children. We …

In Vitro And In Vivo Pharmacodynamic Characterization Of The Novel Plasma Kallikrein Inhibitor Pf-04886847, Dhaval Sanjeev Kolte

Electronic Theses and Dissertations

Plasma kallikrein plays an important role in the pathogenesis of inflammation and thrombosis. Kallikrein cleaves high molecular weight kininogen (HK) to liberate the potent pro-inflammatory peptide bradykinin (BK). BK upon activation of its constitutive B2 receptors on endothelial cells leads to an increase in intracellular Ca2+ level and subsequent production of nitric oxide (NO) and prostacyclin (PGI2), ultimately leading to vasodilation, hypotension, increased vascular permeability and vascular leakage. Further, kallikrein activates the complement system and stimulates neutrophil chemotaxis, aggregation and elastase release. Furthermore, kallikrein mediates the conversion of factor XII (FXII) to activated factor XII (FXIIa) thereby potentiating the intrinsic …