Pharmacy and Pharmaceutical Sciences Commons^™

Phenothiazines And Their Evolving Roles In Clinical Practice: A Narrative Review., Amber N. Edinoff, Grace Armistead, Christina A. Rosa, Alexandra Anderson, Ronan Patil, Elyse M. Cornett, Kevin S. Murnane, Adam M. Kaye, Alan David Kaye

School of Pharmacy Faculty Articles

Phenothiazines, a diverse class of drugs, can be used to treat multiple mental health and physical conditions. Phenothiazines have been used for decades to treat mental illnesses, including schizophrenia, mania in bipolar disorder, and psychosis. Additionally, these drugs offer relief for physical illnesses, including migraines, hiccups, nausea, and vomiting in both adults and children. Further research is needed to prove the efficacy of phenothiazines in treating physical symptoms. Phenothiazines are dopaminergic antagonists that inhibit D2 receptors with varying potency. High potency phenothiazines such as perphenazine are used to treat various psychiatric conditions such as the positive symptoms of schizophrenia, the …

Aduhelm, A Novel Anti-Amyloid Monoclonal Antibody, For The Treatment Of Alzheimer's Disease: A Comprehensive Review., Hannah W. Haddad, Garett W. Malone, Nicholas J. Comardelle, Arielle E. Degueure, Salomon Poliwoda, Rachel J. Kaye, Kevin S. Murnane, Adam M. Kaye, Alan David Kaye

School of Pharmacy Faculty Articles

Alzheimer's disease (AD) is the most common form of dementia affecting millions of individuals, including family members who often take on the role of caregivers. This debilitating disease reportedly consumes 8% of the total United States healthcare expenditure, with medical and nursing outlays accounting for an estimated $290 billion. Cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists have historically been the most widely used pharmacologic therapies for patients with AD; however, these drugs are not curative. The present investigation describes the epidemiology, pathophysiology, risk factors, presentation, and current treatment of AD followed by the role of the novel monoclonal antibody, Adulhelm, in …

Rimegepant For The Treatment Of Migraine., Amnon A. Berger, Ariel Winnick, Austin H. Carroll, Alexandra Welschmeyer, Nathan Li, Marc Colon, Antonella Paladini, Giovanni F. Ramírez, Jamal Hasoon, Elyse M. Cornett, Jaehong Song, Giustino Varrassi, Adam M. Kaye, Alan David Kaye, Latha Ganti

School of Pharmacy Faculty Articles

Migraine is a common form of primary headache, affecting up to 1 in every 6 Americans. The pathophysiology is an intricate interplay of genetic factors and environmental influence and is still being elucidated in ongoing studies. The trigeminovascular system is now known to have a significant role in the initiation of migraines, including the release of pain mediators such as CGRP and substance P. Traditional treatment of migraine is usually divided into acute and preventive treatment. Acute therapy includes non-specific therapy, such as NSAIDs and other analgesics, which may provide relief in mild to moderate migraines. 5-HT1 agonists may provide …

Incorporating Glutamic Acid-Valine-Citrulline Linker In Trifunctional Molecules Targeting Psma Ensures Enhanced Stability, Safety, And Efficacy In Mouse Model Of Prostate Cancer, Toufiq Ul Amin

University of the Pacific Theses and Dissertations

This project describes the development of a new antitumor therapeutic platform that combines the benefits of small-molecule drug conjugates (SMDCs) and antibody drug conjugates (ADCs). Valine-citrulline (VCit) dipeptide linkers are popular cathepsin B cleavable ADC linkers. Due to its instability in mouse serum, translating efficacy data from mouse to human is more difficult. It has been reported that replacing the VCit linker with glutamic acid-valine-citrulline (EVCit) improves ADC stability in mouse serum. The effect of the EVCit linker on the stability of SMDCs has not been reported so far. In a xenograft mouse model of prostate cancer, we found that …

Incidence Of Cancer, Depression, And Economic Burden Of Prescription Nsaids Among Older Adults With Osteoarthritis: Statistical And Machine Learning Approaches, Nazneen Fatima Mohammed Umer Shaikh

Graduate Theses, Dissertations, and Problem Reports (ETD)

Understanding the role of chronic inflammation among older adults is critical because of its implications on chronic inflammatory conditions as well as its interaction with anti-inflammatory medications. Osteoarthritis (OA) is a heterogeneous multi-faceted joint disease with multi-tissue involvement of varying severity, and increasing evidence demonstrates a key role of chronic inflammation in its pathogenesis. Approximately 30 million adults in the United States have OA, and it is reported that a large proportion (43%) of them are older than 65 years. OA is typically treated using non-steroidal anti-inflammatory drugs (NSAIDs) for minimizing pain and reducing inflammation. NSAIDs have consistently shown clinically …

Dna Methylation Pattern Of Cpg Site In The Promoter Region Of Calca-Alpha Gene As A Putative Epigenetic Biomarker In Neonatal Sepsis- A Prospective Observational Study In South India, Rudra Rupesh Reddy Narsapurapu, Deepti Thandaveshwara, Anshu Kumar Yadav, Akila Prashant

Digital Journal of Clinical Medicine

Background: Recently, several studies have been reported on epigenetic modifications of DNA as a predisposing factor for several diseases among neonates and adults. Here we aimed to study the changes in the DNA methylation pattern in the promoter region of the CALCA gene among the neonates suspected to have sepsis in a tertiary care hospital.

Methodology: All the neonates suspected to have sepsis based on the inclusion criteria during the study period were included in the study as cases. Normal healthy neonates were included in the study as controls. Positive cases were isolated from suspected cases based on …

Factors Causing Commercial Leaders In U.S. Multinational Pharmaceutical Businesses To Change Companies, Robert J. Britting Jr

Walden Dissertations and Doctoral Studies

Employee turnover in U.S. multinational pharmaceutical companies remains high, even though U.S. multinational pharmaceutical companies offer competitive salaries and benefits compared to other large industries. A recent survey found that 67% of 2,400 pharmaceutical leaders would be looking for a new job within 12 months and that general employee turnover costs organizations 70% to 300% of each employee's salary. The purpose of this case study was to explore the factors that cause commercial leaders from mid- to large-size U.S. pharmaceutical companies to seek employment outside of their organization. Lewin’s three-stage model of unfreezing, moving, and refreezing, along with the psychology …

Investigation Of Cdk8 Inhibitor Q-12 Effects On Cdk8 And Cdk8 Substrates In Triple Negative Breast Cancer Cell Line Mda-Mb-468, Shengxi Li

University of the Pacific Theses and Dissertations

Cyclin-dependent kinases (CDKs) and cyclins (Cyclins) are the core molecules in the regulation mechanism of the entire cell cycle. Cell cycle dysregulation is a common feature of human cancers, and inhibitors of cyclin-dependent kinases (CDKs) play a crucial role in cell cycle control and are one of the most promising areas of cancer therapy. We aspired to use our cyclin-dependent kinase 8 (CDK8) inhibitor, Q-12, as a probe for biomarker discovery for CDK8 inhibitor sensitive tumor types. Q-12 shows potent inhibition of cell viability and induction of apoptosis process in some triple-negative breast cancer (TNBC) and colorectal cancer cell lines …

Optimization Of The Structure Of Ttr Ligands For Half-Life Extension (Tlhe), Guanming Jiang

University of the Pacific Theses and Dissertations

Many potential therapeutic agents face challenges for their clinical development due to short circulation half-life. As a result, prolonging the half-life of therapeutic drugs in circulation while preserving their hydrophilicity and small size will be a key step toward more effective and safe pharmacological molecules. Our lab developed a new approach for enhancing the safety and efficacy of therapeutic agents. By endowing therapeutic agents with a hydrophilic small molecule (a derivative of the clinical candidate, AG10) which reversibly binds to the serum protein transthyretin (TTR), the half-life of the therapeutic agent should be extended by binding to the TTR in …

Expression Of Mouse Full-Length Aryl Hydrocarbon Receptor And Human Aryl Hydrocarbon Receptor Ligand Binding Domain In Pichia Pastoris, Yiyuan Wang

University of the Pacific Theses and Dissertations

Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that regulates biological responses to planar aromatic hydrocarbon. AHR activates gene transcription by binding to its corresponding enhancer with its partner-aryl hydrocarbon receptor nuclear translocator (ARNT). In addition, this receptor has been shown to regulate xenobiotic-metabolizing enzymes such as cytochrome P450. AHR exists widely in body tissues and affects bioactivation of carcinogenic compounds, T cell differentiation, fatty acid synthesis, cell proliferation, hematopoietic stem cell differentiation, respiratory reactivity, and insulin sensitivity. Although the precise mechanism illustrating the endogenous AHR function remains unclear, there has been intense interest in exploring AHR as a …

Optimizing The Human Aryl Hydrocarbon Receptor (Hahr) Expression In Pichia Pastoris, Junyu Qian

University of the Pacific Theses and Dissertations

The aryl hydrocarbon receptor (AHR) is a transcription factor which heterodimerizes with the aryl hydrocarbon receptor nuclear translocator (Arnt) to regulate downstream gene transcription. For the purpose of studying the crystal structure of human aryl hydrocarbon receptor (hAHR), it is essential to obtain abundant amount of pure recombinant protein.Basing on the benefits of using P. pastoris system to produce recombinant protein, including appropriate folding, secretion of interest proteins to the external environment of the cell, and easier purification process of protein due to the its limited production of endogenous secretory proteins [1], our lab chose P. pastoris yeast as the …

Peripherally Restricted Delivery System Provides Insights On The Role Of Cns In Precipitating Opioid-Induced Constipation, Dengpan Liang

University of the Pacific Theses and Dissertations

A serious opioid crisis is affecting public health and economics, eroding people’s quality of life. 80% of patients who receive opioids suffer from adverse effects such as Opioid-induced constipation (OIC). However, there is no efficient medicine for these adverse effects. Notably, mainstream theory supports that analgesia effects are mainly controlled by CNS while OIC is predominately controlled by peripheral. In addition, the sites of action of opioid was based on the assumption that mu-opioid receptor antagonists (PAMORAs), did not cross the blood-brain barrier (BBB). Unfortunately, the BBB crossing of PAMORAs mislead the understanding of the role of the central nervous …

Thermodynamic Mechanisms Of Helix Stabilization In A Model Peptide And Protein, Ryan Murray

University of the Pacific Theses and Dissertations

Biologics are large, complex therapeutic agents generally produced from living organisms. One group of biologics is peptide/protein based. Biological agents offer unique advantages over traditional therapeutics including longer half-lives, higher specificity, greater efficacy, and reduced off-target effects. However, protein/peptide based drugs suffer from both delivery and stability issues. The higher order of protein structures (secondary, tertiary, etc.) derive ~80% of their conformational stability from paltry hydrophobic effects, with net stabilization of 5-15 kcal/mole observed for many proteins. Loss of conformational stability can lead to increased aggregation, precipitation, and degradation; and reduced activity and side effects. To increase stability and improve …

Peripherally Restricted Opioid Conjugates And Its Use As Pharmacological Probes And Potential Therapeutics, Md Tariqul Haque Tuhin

University of the Pacific Theses and Dissertations

Opioid-induced constipation (OIC) is one of the major adverse effects of opioid analgesics used by millions of patients each year. While progress has been made, there remains a significant unmet medical need in the treatment of OIC. Major gaps remain in our understanding of the role of the gastrointestinal tract and central nervous system (CNS) in precipitating OIC. For the last four decades, numerous investigations to study the sites of action of opioid analgesics have utilized peripherally acting mu-opioid receptor antagonists (PAMORAs), which have been incorrectly believed to have limited penetration across the blood-brain barrier (BBB). Several preclinical and clinical …

Design And Synthesis Of Curcumin Analogs For Anticancer Activity And Discovery Of Novel Hit Molecules Targeting Cxcr4., Maryam Sadat Hosseini Zare

Dissertations (2016-Present)

Curcumin as a natural compound is made of various components including protein, carbohydrate, and curcuminoid. Curcuminoid is made of curcumin, desmethoxycurcumin and bis desmethoxycurcumin. Curcumin is used for the treatment of cancer and inflammatory disorders, but it has some therapeutic problems like poor bioavailability, poor efficacy, and chemical instability. To overcome these problems, the objective of this study is (1) synthesis of pyrazole curcumin analogs, (2) synthesis of triazole curcumin analogs, and (3) in-vitro study of the anticancer activity of these curcumin analogs on head & neck, breast, pancreatic and glioblastoma cancer cells. During this part of my Ph.D. project, …

Epithelial Immunomodulation By Aerosolized Toll-Like Receptor Agonists Prevents Allergic Inflammation In Airway Mucosa In Mice, David L Goldblatt, Gabriella Valverde Ha, Shradha Wali, Vikram V Kulkarni, Michael K Longmire, Ana M Jaramillo, Rosha P Chittuluru, Adrienne Fouts, Margarita Martinez-Moczygemba, Jonathan T Lei, David P Huston, Michael J Tuvim, Burton F Dickey, Scott E Evans

Faculty, Staff and Student Publications

Allergic asthma is a chronic inflammatory respiratory disease associated with eosinophilic infiltration, increased mucus production, airway hyperresponsiveness, and airway remodeling. Epidemiologic data reveal that the prevalence of allergic sensitization and associated diseases has increased in the twentieth century. This has been hypothesized to be partly due to reduced contact with microbial organisms (the hygiene hypothesis) in industrialized society. Airway epithelial cells, once considered a static physical barrier between the body and the external world, are now widely recognized as immunologically active cells that can initiate, maintain, and restrain inflammatory responses, such as those that mediate allergic disease. Airway epithelial cells …

Design And Synthesis Of Tetrahydrocurcumin-Amino Acid Conjugates For Cytotoxicity Enhancement Against Brain Cancer C6 Cells, Polsak Teerawonganan

Chulalongkorn University Theses and Dissertations (Chula ETD)

The L-type amino acid transporter I (LAT1) is an attractive target for drug development in glioma with a poor prognosis. LAT1 facilitates the cross-membrane transport of essential amino acids and plays a crucial role in cancer cell proliferation and growth. In this study, a novel series of tetrahydrocurcumin (THC)-amino acid conjugates were synthesized by conjugating four amino acids: glycine (Gly), leucine (Leu), isoleucine (Ilu), and phenylalanine (Phe) to THC via carbamate bonds to improve the anticancer effects of THC by mediating LAT1. The therapeutic efficacy of THC-amino acid conjugates was further examined in C6 glioma cells, including the role of …

Wet Granulation Process Design For In-Situ Polymorphic Transformation Of Clopidogrel Bisulfate Tablets, Supattarayaporn Phaopongthai

Chulalongkorn University Theses and Dissertations (Chula ETD)

Clopidogrel bisulfate (CLP) is an antiplatelet agent which can exist in six polymorphic forms (Form I, II, III, IV, V, and VI) and polyamorphous form. The aim of this study was to investigate and apply the factors that affect in-situ polymorphic transformation of CLP (Form II) during the wet granulation process to control the production process of CLP tablets to have the desired amorphous form. Initially, solid state stability of CLP (Form II) was evaluated and revealed that CLP (Form II) was highly thermally stable when exposed to heat up to 80oC for 120 minutes. The wet granulation process of …

ผลการลดปริมาณการใช้มอร์ฟีน เมื่อเปรียบเทียบระหว่างการให้ยานีโฟแพมทางหลอดเลือดดำอย่างมีเว้นระยะกับอย่างต่อเนื่องในผู้ป่วยหลังเข้ารับการผ่าตัดเปลี่ยนข้อเข่าเทียม, วรธนรรถ คชาชีวะ

Chulalongkorn University Theses and Dissertations (Chula ETD)

การศึกษาเชิงทดลองแบบสุ่มนี้ มีวัตถุประสงค์เพื่อเปรียบเทียบปริมาณการใช้มอร์ฟีนสะสมในเวลา 48 ชั่วโมง ระหว่างการให้ยานีโฟแพมทางหลอดเลือดดำอย่างมีเว้นระยะ (intermittent infusion, II) และอย่างต่อเนื่อง (continuous infusion, CI) เมื่อให้ร่วมกับยาระงับปวดแบบผสมผสานอื่น ในผู้ป่วยผ่าตัดเปลี่ยนข้อเข่าเทียม ผู้ป่วยที่เข้ารับการผ่าตัดเปลี่ยนข้อเข่าเทียมแบบปฐมภูมิจำนวน 58 คน จะถูกสุ่มด้วยโอกาสเท่ากันให้ได้รับยานีโฟแพม 20 มิลลิกรัม หยดเข้าทางหลอดเลือดดำในเวลา 1 ชั่วโมง ให้ซ้ำทุก 6 ชั่วโมง หรือ นีโฟแพม 80 มิลลิกรัม หยดเข้าทางหลอดเลือดดำอย่างต่อเนื่องเป็นเวลา 24 ชั่วโมง ผู้ป่วยจำนวน 3 คน ต้องหยุดการศึกษาเนื่องจากเกิดอาการไม่พึงประสงค์ (1 คนจากกลุ่ม II และ 2 คนจากกลุ่ม CI) ลักษณะประชากรไม่มีความแตกต่างกันระหว่างสองกลุ่มการศึกษา วัดผลเป็นปริมาณการใช้มอร์ฟีนสะสม ในเวลา 48 ชั่วโมงจากเครื่อง intravenous patient-controlled analgesia (IV PCA) และคะแนนความปวดทุก 4 ชั่วโมง ผลการศึกษาพบว่า ปริมาณการใช้มอร์ฟีนสะสมในเวลา 48 ชั่วโมง ไม่มีความแตกต่างกัน [median (range): 4 มิลลิกรัม (0 - 12) ในกลุ่ม II และ 6 มิลลิกรัม (0 - 18) ในกลุ่ม CI; p = 0.579] คะแนนความปวดแตกต่างกันที่เวลา 4 ชั่วโมง กลุ่ม II มีคะแนนความปวดต่ำกว่ากลุ่ม CI [median (range): 0 (0 - 4) ในกลุ่ม II และ 0 (0 …

Development And In Vitro Cytotoxicity Evaluation In Breast Cancer Cells Of Lutein-Loaded Magnetic Chitosan/Alginate Nanoparticles, Bryan Paul Bulatao

Chulalongkorn University Theses and Dissertations (Chula ETD)

Magnetic drug targeting can be a strategy to overcome the limitations of delivering phytochemicals for effective cancer treatment. Here, we demonstrate the benefits of magnetic targeting delivery using a combination of chitosan (CS) and alginate (Alg) as materials in encapsulating lutein (lut) and magnetite (Fe3O4) to increase the cytotoxicity of lutein against breast cancer cells with or without magnetic stimulation. The formulation was optimized by a statistical approach using response surface methodology (RSM) based on the Box-Behnken design (BBD). The optimized lut-CS/Alg-Fe3O4 nanoparticles exhibited desirable characteristics including nanosize with monodispersity, highly crystalline Fe3O4 core, good stability, high saturation magnetization, and …