Medicinal and Pharmaceutical Chemistry Commons^™

Stability Evaluation Of Extemporaneously Compounded Vancomycin Ophthalmic Drops: Effect Of Solvents And Storage Conditions, Christopher Ross, Basir Syed, Joanna Pak, Vishal Jhanji, Jason Yamaki, Ajay Sharma

Pharmacy Faculty Articles and Research

Vancomycin is the drug of choice for methicillin-resistant Staphylococcus aureus keratitis and other ocular infections. Vancomycin ophthalmic drops are not commercially available and require compounding. The present study was designed to investigate the stability of vancomycin ophthalmic drops in normal saline, phosphate-buffered saline (PBS), and balanced salt solution (BSS) while stored at room temperature or under refrigeration. Vancomycin ophthalmic drops (50 mg/mL) were aseptically prepared from commercially available intravenous powder using PBS, BSS, and saline. Solutions were stored at room temperature and in a refrigerator for 28 days. The vancomycin stability was tested by a microbiology assay and high-performance liquid …

Sars-Cov-2 Early Infection Signature Identified Potential Key Infection Mechanisms And Drug Targets, Yue Li, Ashley Duche, Michael R. Sayer, Don Roosan, Farid G. Khalafalla, Rennolds S. Ostrom, Jennifer Totonchy, Moom Roosan

Pharmacy Faculty Articles and Research

Background

The ongoing COVID-19 outbreak has caused devastating mortality and posed a significant threat to public health worldwide. Despite the severity of this illness and 2.3 million worldwide deaths, the disease mechanism is mostly unknown. Previous studies that characterized differential gene expression due to SARS-CoV-2 infection lacked robust validation. Although vaccines are now available, effective treatment options are still out of reach.

Results

To characterize the transcriptional activity of SARS-CoV-2 infection, a gene signature consisting of 25 genes was generated using a publicly available RNA-Sequencing (RNA-Seq) dataset of cultured cells infected with SARS-CoV-2. The signature estimated infection level accurately in …

Understanding Molecular Interaction Between Sulfadoxine And Human Serum Albumin Through Spectroscopic And Molecular Docking Methods, Jaslene Anne Francis

Student Works (2020-2029)

The main aim of this study was to characterize the molecular interaction between sulfadoxine (SDN) and the major transport protein in the blood plasma, human serum albumin (HSA) using fluorescence, absorption, circular dichroism and voltammetric techniques along with computational methods. SDN-induced changes in the fluorescence intensity of HSA hinted the complex formation between SDN and HSA. Both values of the bimolecular quenching rate constant and UV-Vis absorption spectral results characterized the quenching of HSA fluorescence as static quenching. Analysis of the quenching results showed a moderate binding affinity (Ka = 3.39×104 M‒1 at 300 K) between SDN and HSA. Thermodynamic …

Repurposing Of Omarigliptin As A Neuroprotective Agent Based On Docking With A2a Adenosine And Ache Receptors, Brain Glp-1 Response And Its Brain/Plasma Concentration Ratio After 28 Days Multiple Doses In Rats Using Lc-Ms/Ms, Bassam Ayoub, Haidy Michel, Shereen Mowaka, Moataz S. Hendy, Mariam M. Tadros

Pharmacy

Abstract: The authors in the current work suggested the potential repurposing of omarigliptin (OMR) for neurodegenerative diseases based on three new findings that support the preliminary finding of crossing BBB after a single dose study in the literature. The first finding is the positive results of the docking study with the crystal structures of A2A adenosine (A2AAR) and acetylcholine esterase (AChE) receptors. A2AAR is a member of non-dopaminergic GPCR superfamily receptor proteins and has essential role in regulation of glutamate and dopamine release in Parkinson’s disease while AChE plays a major role in Alzheimer’s disease as the primary enzyme responsible …

Label‑Free Spectral Imaging To Study Drug Distribution And Metabolism In Single Living Cells, Qamar Alshammari, Rajasekharreddy Pala, Nir Katzir, Surya M. Nauli

Pharmacy Faculty Articles and Research

During drug development, evaluation of drug and its metabolite is an essential process to understand drug activity, stability, toxicity and distribution. Liquid chromatography (LC) coupled with mass spectrometry (MS) has become the standard analytical tool for screening and identifying drug metabolites. Unlike LC/MS approach requiring liquifying the biological samples, we showed that spectral imaging (or spectral microscopy) could provide high-resolution images of doxorubicin (dox) and its metabolite doxorubicinol (dox’ol) in single living cells. Using this new method, we performed measurements without destroying the biological samples. We calculated the rate constant of dox translocating from extracellular moiety into the cell and …

The Mechanism Of Β-N-Methylamino-L-Alanine Inhibition Of Trna Aminoacylation And Its Impact On Misincorporation, Nien-Ching Han, Tammy J. Bullwinkle, Kaeli F. Loeb, Kym F. Faull, Kyle Mohler, Jesse Rinehart, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

β-N-methylamino-l-alanine (BMAA) is a nonproteinogenic amino acid that has been associated with neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). BMAA has been found in human protein extracts; however, the mechanism by which it enters the proteome is still unclear. It has been suggested that BMAA is misincorporated at serine codons during protein synthesis, but direct evidence of its cotranslational incorporation is currently lacking. Here, using LC-MS–purified BMAA and several biochemical assays, we sought to determine whether any aminoacyl-tRNA synthetase (aaRS) utilizes BMAA as a substrate for aminoacylation. Despite BMAA's previously predicted misincorporation at serine …

Formulation And Characterization Of Beeswax/Rosemary Oil Nanostructured Lipid Carrier For Drug Delivery System, Mohd Latif Farhanim

Student Works (2020-2029)

A stable colloidal suspension of nanostructured lipid carriers (NLCs) was synthesized from natural source of lipid. The toxicity and insolubility of drugs in water remain a significant problem and has led to the development of food-grade drug delivery systems such as nanostructured lipid carriers (NLCs). NLCs composing various amount of beeswax (BW), rosemary oil (RO) and poloxamer 188 (P188) were prepared by melt-emulsification combined with ultrasonication method. The physicochemical properties of NLC also were determined. Optimization of the formulation (F) was performed based on the criteria of stability. Formulation with the smallest particle size and highest magnitude of zeta potential …

Synergistic Interactions Of Ionic Liquids And Antimicrobials Improve Drug Efficacy., Daniel D Yang, Nicholas J Paterna, Alexandria S Senetra, Kaitlyn R Casey, Phillip D Trieu, Gregory A. Caputo, Timothy Vaden, Benjamin Carone

College of Science & Mathematics Departmental Research

Combinations of ionic liquids (ILs) with antimicrobial compounds have been shown to produce synergistic activities in model liposomes. In this study, imidazolium chloride-based ILs with alkyl tail length variations are combined with commercially available, small-molecule antimicrobials to examine the potential for combinatorial and synergistic antimicrobial effects on P. aeruginosa, E. coli, S. aureus, and S. cerevisiae. The effects of these treatments in a human cell culture model indicate the cytotoxic limits of ILs paired with antimicrobials. The analysis of these ILs demonstrates that the length of the alkyl chain on the IL molecule is proportional to both antimicrobial activity and …

[(Wr)8Wkβa]-Doxorubicin Conjugate: A Delivery System To Overcome Multi-Drug Resistance Against Doxorubicin, Khalid Zoghebi, Hamidreza Montazeri Aliabadi, Rakesh Kumar Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

Doxorubicin (Dox) is an anthracycline chemotherapeutic agent used to treat breast, leukemia, and lymphoma malignancies. However, cardiotoxicity and inherent acquired resistance are major drawbacks, limiting its clinical application. We have previously shown that cyclic peptide [WR]₉ containing alternate tryptophan (W) and arginine (R) residues acts as an efficient molecular transporter. An amphiphilic cyclic peptide containing a lysine (K) residue and alternative W and R was conjugated through a free side chain amino group with Dox via a glutarate linker to afford [(WR)₈WKβA]-Dox conjugate. Antiproliferative assays were performed in different cancer cell lines using the conjugate and the …

A Global Review On Short Peptides: Frontiers And Perspectives, Vasso Apostolopoulos, Joanna Bojarska, Tsun-Thai Chai, Sherif Elnagdy, Krzysztof Kaczmarek, John Matsoukas, Roger New, Keykavous Parang, Octavio Paredes Lopez, Hamideh Parhiz, Conrad O. Perera, Monica Pickholz, Milan Remko, Michele Saviano, Mariusz Skwarczynski, Yefeng Tang, Wojciech M. Wolf, Taku Yoshiya, Janusz Zabrocki, Piotr Zielenkiewicz, Maha Alkhazindar, Vanessa Barriga, Konstantinos Kelaidonis, Elham Mousavinezhad Sarasia, Istvan Toth

Pharmacy Faculty Articles and Research

Peptides are fragments of proteins that carry out biological functions. They act as signaling entities via all domains of life and interfere with protein-protein interactions, which are indispensable in bio-processes. Short peptides include fundamental molecular information for a prelude to the symphony of life. They have aroused considerable interest due to their unique features and great promise in innovative bio-therapies. This work focusing on the current state-of-the-art short peptide-based therapeutical developments is the first global review written by researchers from all continents, as a celebration of 100 years of peptide therapeutics since the commencement of insulin therapy in the 1920s. …

Pharmacist-Led Programs To Increase Statin Prescribing: A Narrative Review Of The Literature, Mary Elkomos, Raha Jahromi, Michael S. Kelly

Pharmacy Faculty Articles and Research

Statins are lipid-lowing medications shown to reduce cardiovascular events and are recommended for specific patient populations at elevated risk of atherosclerotic cardiovascular disease (ASCVD). Despite the demonstrated efficacy of statins for reducing ASCVD risk, and guidance on which populations should receive statin therapy, a substantial portion of eligible patients are not prescribed statin therapy. Pharmacists have attempted to increase the number of eligible patients receiving appropriate statin therapy through a variety of interventions and across several clinical settings. In this article, we highlight multiple studies evaluating the effectiveness of pharmacist-led interventions to improve statin use. A total of seven studies …

Differential Modulation Of Sk Channel Subtypes By Phosphorylation, Young-Woo Nam, Dezhi Kong, Dong Wang, Razan Orfali, Rinzhin T. Sherpa, Jennifer Totonchy, Surya M. Nauli, Miao Zhang

Pharmacy Faculty Articles and Research

Small-conductance Ca²⁺-activated K⁺ (SK) channels are voltage-independent and are activated by Ca²⁺ binding to the calmodulin constitutively associated with the channels. Both the pore-forming subunits and the associated calmodulin are subject to phosphorylation. Here, we investigated the modulation of different SK channel subtypes by phosphorylation, using the cultured endothelial cells as a tool. We report that casein kinase 2 (CK2) negatively modulates the apparent Ca²⁺ sensitivity of SK1 and IK channel subtypes by more than 5-fold, whereas the apparent Ca²⁺ sensitivity of the SK3 and SK2 subtypes is only reduced by ∼2-fold, when heterologously …

Drug Delivery Systems: Exploring Rheological Properties And Therapeutic Effect Of 5-Fu Chitosan Gel For Topical Wound Healing, Samuel Tetteh-Quarshie

Theses, Dissertations and Capstones

Diabetic skin wound is a common complication of diabetes that occurs in about 15% of diabetic patients and often requires prolonged hospitalization for its management and treatment. Natural polymers are used for wound dressing due to their biological adhesiveness, non-toxicity, and biodegradable nature. 5-Fluorouracil (FU) has been shown to alter adipokine expression which is implicated in cutaneous wound repair. Thus, our overall objective was to investigate the utility of chitosan (CS) gel for topical delivery of 5-FU to treat diabetic wounds. We prepared chitosan gel (2% w/w) in serial dilutions of 5-FU (25μg/mL, 2.5μg/mL, 0.25μg/mL, and 0.025μg/mL) and evaluated their …

Mechanisms Of Apoptosis Induced By Actinomycin D In Aerodigestive Tract Cancers, Adeoluwa Ayodeji Adeluola

Theses, Dissertations and Capstones

Upper aerodigestive tract cancers including cancers of the oral cavity, pharynx, larynx, esophagus, and lungs are the most prevalent cancers and leading causes of cancer-related deaths. Collectively, over 300,000 new cases and 146,500 deaths are projected within the US in the year 2021. Drug-associated toxicities, as well as resistance to therapy (intrinsic and acquired), are big challenges for successfully treating these cancers. Recent studies have shown that combining low-dose actinomycin D with existing therapies is a promising strategy to reduce toxicity (cyclotherapy) and to overcome resistance. The development of these treatment strategies however requires an understanding of the molecular mechanisms …

The Development Of A Cancer-Targeting Peptide-Drug Conjugate For The Treatment Of Melanoma, Cassandra Dill

Pharmaceutical Sciences (MS) Theses

Cancer is an ongoing global pandemic which has caused a dramatic shift in research priorities. One of the most aggressive and difficult to treat has invariably remained metastatic melanoma. Although encompassing only 4% of overall skin cancer diagnoses, chances for recovery were slim until recent revolutionary development of immunotherapy adding to its regimen spectrum. This is due to its resistance to many standard-of-care treatment methods, along with its relatively high-metastatic potential. Within the past decade, eight new targeted and immune checkpoint inhibitors have gained FDA approval. The median life survival has increased significantly from 9 months to over 2 years …

Science-Based Regulation Of Pharmacological Substances In Competition Horses, Jacob Machin

Theses and Dissertations--Toxicology and Cancer Biology

Current testing methodologies within equine forensic toxicology focus on arbitrary thresholds and zero-tolerance policy. Modern analytical chemistry’s limits of detection are low enough that oftentimes femtogram-per-milliliter amounts of a substance can readily be identified in both blood and urine of a horse. For most pharmacologically relevant compounds, these concentrations have no relevance to pharmacological effect. It is therefore crucial that testing methodologies to determine appropriate thresholds and cut-offs be developed that are driven by biological activity rather than arbitrary limits of detection. This dissertation looks to address this by suggesting a system of calculated Effective Plasma Concentrations by which a …

Standardization Of E-Cigarette Research: Addressing The Analysis Of Total Nicotine And Free Base Nicotine In E-Cigarettes, Vinit Gholap

Theses and Dissertations

Electronic cigarettes (e-cigarettes) are one of the major sources of exposure to nicotine, an addictive chemical. Since 2016, the Food and Drug Administration (FDA) has started regulating these products under the Tobacco Control Act yet, specifications about the nicotine content in these products have not been established. In e-cigarettes, nicotine concentration ranges from 0 to >50mg/mL. Additionally, several e-cigarette related parameters have been identified which can affect nicotine delivery to users. Of these factors, nicotine forms (protonated and free base) have been found to play a significant role in nicotine absorption profiles yet, a limited and contradictory research is available …

Delineating The Biosynthesis Of Capuramycin-Type Antibiotics, Ashley L. Biecker

Theses and Dissertations--Pharmacy

New antibiotic scaffolds with novel drug targets are needed to combat the rise of drug-resistant, infectious microorganisms. The bacterial translocase I is a ubiquitous enzyme in the peptidoglycan biosynthetic pathway that has yet to be targeted by clinically used antibiotics. It catalyzes the transfer of N-acetylmuramoyl-pentapeptide to undecaprenylphosphate in order to generate lipid I during cell wall biosynthesis. A screening of bacterial translocase I inhibitors led to the discovery of the novel compound capuramycin and its analogues: A-500359s, A-503083s, and A-102395, produced by various species of actinomycetes. The capuramycins show potent activity against the bacterial translocase I with IC50s …

Pharmacogenomics And Ssris Appropriateness In Older Community Dwelling African Americans, Wint War Phyo, Lana Sargent, Elvin T. Price

Graduate Research Posters

Background: Depressive and anxiety disorders are among the most common illnesses experienced by older adults (age > 60). The selective serotonin reuptake inhibitors (SSRIs) are preferred class of antidepressants for these disorders due to their high efficacy and safety profiles among older adults. However, SSRIs are metabolized by highly polymorphic cytochrome P450 enzymes, specifically CYP2D6 and CYP2C19. This can lead to variable dose-response outcomes, especially among older African American population.

Objective: Analyze the frequency of CYP2D6 and CYP2C19 polymorphisms in African American older adults who are taking SSRIs and identify potential inappropriate use of SSRIs in these older adults using the …

Systematic Structure-Activity Relationship Studies Of Nalfurafine, Mengchu Li

Theses and Dissertations

Today’s opioid crisis is one of the most challenging public health emergency. Two million Americans suffer opioid addiction. Over 20 million adults are affected by daily pain without non-addictive analgesics.

Kappa opioid receptor (KOR) is one of the most studied new pain targets void of abuse liability. KOR agonists have shown potent analgesia and also potential in alleviating opioid addiction. The only approved KOR agonist in clinic is nalfurafine (NFU). Though not leading to addiction, the analgesic effects of NFU are accompanied by sedative side effects. Therefore, we designed a systematical structure-activity relationship study of NFU for developing non-addictive analgesics. …

Bisphosohoglycertae Mutase: A Potential Target For Sickle Cell Disease, Anfal S. Aljahdali

Theses and Dissertations

Bisphosphoglycerate mutase (BPGM) is a part of the erythrocyte glycolysis system. Specifically, it is a central enzyme in the Rapoport-Leubering pathway, a side glycolytic pathway involved in the regulation of the concentration of the natural allosteric effector of hemoglobin (Hb), 2,3-bisphosphoglycerate (2,3-BPG). BPGM catalyses the synthesis and hydrolysis of 2,3-BPG through its synthase and phosphatase activities. The synthase activity is the main role of BPGM, while the phosphatase activity is low and is activated by the physiological effector, 2-phosphoglycolate (2-PG) with the latter mechanism poorly understood.

BPGM activity and 2,3-BPG levels in red blood cells (RBCs) have a significant role …

Mechanistic Insights Of Mitochondrial Reactive Oxygen Species In Alzheimer's Disease Models, Jakob C. Green

Theses and Dissertations

Alzheimer’s disease (AD) is a neurodegenerative disease that results in impaired cognition, disorientation, confusion, poor judgement, and behavioral changes. The mitochondrial cascade hypothesis (MCH), which postulates that accumulating oxidative stress and mitochondrial dysfunction plays an integral role in the development of the disease, potentially upstream, in conjunction with or independent of Aβ and tau. The literature supports the critical role of mitochondrial dysfunction in the progression and development of AD, but is inconclusive about what precise role, as initiator or delegate, it performs. Regardless, the impact that oxidative stress and mitochondrial dysfunction have on AD deserves further study and investigation. …

Glycosaminoglycan Modulation Of Key Proteins In Alzheimer's Disease, Tamim Chiba

Theses and Dissertations

Glycosaminoglycans (GAGs) are linear polysaccharides whose disaccharide building blocks consist of an amino sugar (D-glucosamine) and either uronic acid (D-glucuronic acid or L-iduronic acid) or galactose. Nearly all GAGs (with the exception of hyaluronic acid) are covalently attached to proteins, forming proteoglycans, and are ubiquitous in nature. The monomeric units, chain length, degree and pattern of sulfation, and epimerization are important properties that determine the influence of these molecules. Through Coulombic forces, hydrogen bonds and hydrophobic interactions, they regulate many physiological and pathophysiological processes such as blood coagulation, cell growth and differentiation, inflammatory processes, host defense and viral infection mechanisms. …

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 …

Exploring The Dopamine Transporter Utilizing A Two-Pronged Approach With Novel Cathinone Analogs And Mutant Dopamine Transporters, Charles B. Jones Iii

Theses and Dissertations

The dopamine transporter (DAT) is responsible for the removal of the neurotransmitter from the synaptic gap and a therapeutic target for a multitude of drugs. While the ortholog Drosophila melanogaster dopamine transporter (dDAT) and human serotonin transporter (hSERT) have resolved structures, the human dopamine transporter (hDAT) does not. A 3-D computational homology model of hDAT was constructed for the study of molecular interactions with agents within the central binding site (S1) of the transporter.

Synthetic cathiones are a class of abused stimulant drugs that primarily target DAT. Greater than 150 cathinones have been identified on the clandestine market but there …

Development Of Sam-Based Chemical Probes For Methyltransferases, Daniel V. Mongeluzi

Theses and Dissertations

Fig.1. SAM analog for the profiling of MTase activity. A. Chemical structure of probe 1; B. General scheme of the labeling and capture strategy.

A

B

Methylation is a fundamental mechanism used in the biological system to modify the structure and function of biomolecules such as proteins, DNA, RNA, and metabolites.¹ Methyl groups are installed by a large and diverse class of S-adenosyl-L-methionine (SAM)-dependent methyltransferases (MTases), which transfer the sulfonium methyl group of SAM to either carbon, nitrogen, oxygen, or other heteroatoms on biomolecules.² Dysregulated MTase activity contributes to numerous diseases, including cancer, metabolic disorders, neurodegenerative diseases. …

Peptidomimetic And Non- Peptidomimetic Derivatives As Possible Sars-Cov-2 Main Protease (Mpro) Inhibitors, Mohammed A. Al Awadh, Mohini S. Ghatge Ph.D, Mona A. Al Khairi, Faik N. Musayev, Akua K. Donkor, Mohammed H. Al Mughram, Abdelsattar M. Omar Ph.D, Moustafa M. El-Araby Ph.D, Martin K. Safo Ph.D

Graduate Research Posters

To design novel inhibitors of the SARS-CoV-2 main protease (Mpro), we investigated the binding mode of the recently reported α-ketoamide inhibitors of this enzyme. Following, we utilized in-silico screening to identify 168 peptidomimetic and non-peptidomimetic compounds that are high probability Mpro binding candidates. The compounds were synthesized in 5 to 10 mg for initial screening for their potential inhibition of Mpro using Fluorescence Resonance Energy Transfer (FRET) assay. The study was conducted using the main protease, MBP-tagged (SARS-CoV-2) Assay Kit (BPS Bioscience, #79955-2), and the fluorescence due to enzymatic cleavage of substrate measured using BMG LABTECH CLARIOstar™, a fluorescent microplate …

Investigating The Effect Of Khat (Catha Edulis) On Selected Obesity Markers And Pathways In C57bl/6j Male Mice, Mustafa Ahmed Al-Shagga

Student Works (2020-2029)

In East African and South Western Arabian populations, Catha edulis (khat) is believed to suppress appetite and reduce body weight. First, this study conducted a systematic review of the literature on the effects of khat and its active alkaloid cathinone on body weight and appetite regulation. Second, this study investigated the effect of khat and cathinone on selected metabolic and histopathologic parameters and their influence on the expression of obesity-related genes in high-fat diet-induced obese mice. Forty-two male C57BL/6J mice were divided into seven groups (n= 6); normal diet control treated with vehicle (NDC), normal diet treated with 200 mg/kg …

Development Of Miriplatin-Loaded Nanoparticles Against Non-Small Cell Lung Cancer, Zhongyue Yuan

University of the Pacific Theses and Dissertations

Lung cancer claims the highest mortality and the second-most estimated new cases among all oncological diseases [1]. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all newly diagnosed lung cancers [2]. Approximately 40% of newly diagnosed lung cancer patients are stage IV. For stage IIIB/IV NSCLC, cytotoxic combination chemotherapy is standard first-line chemotherapy. A regimen of platinum (cisplatin or carboplatin) plus paclitaxel, gemcitabine, docetaxel, vinorelbine, irinotecan, or pemetrexed is the recommended clinical treatment [3].

Cisplatin is the first-generation platinum-based anti-cancer drug. Although cisplatin is much more effective than other platinum drugs at the same dosage [4], accumulating reports …

Impact Of 17-Beta Estradiol And Moderate-Intensity Exercise On Mesenteric Arterial Function Of Uc Davis Type-2 Diabetes Mellitus Rats, Md Rahatullah Razan

University of the Pacific Theses and Dissertations

The studies in this dissertation were designed to investigate the impacts of estrogen (17-β estradiol/E2) and moderate-intensity exercise (MIE) on the mesenteric arterial (MA) function of the University of California Davis type-2 diabetes mellitus (UCD-T2DM) Rat model. Our recent report suggests that diabetes impairs MA vasorelaxation in both sexes of the UCD-T2DM model. Particularly, we reported that MA from prediabetic male rats showed a greater impairment compared to that in prediabetic females. However, when females become diabetic, they exhibit a greater vascular dysfunction than males. Therefore, the aim of the first study was to investigate whether female sex hormone, specifically …