Pharmacy and Pharmaceutical Sciences Commons^™

Development And Validation Of Triticum Phytobiological Method As An Alternative Procedure For Investigating In Vivo Acute Toxicity On Mice, Emil Ştefănescu, Aurelia N. Cristea, Cornel Chiriță, Octavian Olaru, Adriana Anghel, Mihaela Dinu

Journal of Mind and Medical Sciences

The goal of this study was to validate an alternative method for determining in vivo acute toxicity using vegetal material instead of laboratory animals, starting from the phytobiological method known also as the Triticum technique. We set out to demonstrate that vegetal cells have similar sensitivity to some toxic agents as animal cells, in which case a statistical correlation could be established. A series of new compounds synthesized by the Romanian National Institute for Chemical Pharmaceutical Research and Development as potential β3 adrenergic receptors agonists were tested for their acute toxicity using classic animal exposure models, before investigating possible anti-diabetic …

A Mathematical Analysis Of Drug Dissolution In The Usp Flow Through Apparatus, David Mcdonnell, Deirdre M. D'Arcy, Lawrence J. Crane, Brendan Redmond

Articles

This paper applies boundary layer theory to the process of drug dissolution in the USP (United States Pharmacopeia) Flow Through Apparatus. The mass transfer rate from the vertical planar surface of a compact within the device is examined. The theoretical results obtained are then compared with those of experiment. The paper also examines the effect on the dissolution process caused by the interaction between natural and forced convection within the apparatus and the introduction of additional boundaries.

The Influence Of A Kdt501, A Novel Isohumulone, On Adipocyte Function In Humans, Brian S. Finlin, Beibei Zhu, Bernard P. Kok, Cristina Godio, Philip M. Westgate, Neile Grayson, Robert Sims, Jeffrey S. Bland, Enrique Saez, Philip A. Kern

Internal Medicine Faculty Publications

Objective: In a phase II clinical trial in nine obese, insulin-resistant humans, we observed that treatment with KDT501, a novel isohumulone drug, increased total and high-molecular weight (HMW) adiponectin in plasma. The objective was to determine whether KDT501 increased adiponectin secretion from subcutaneous white adipose tissue (SC WAT) and the underlying mechanism(s).

Methods: Nine obese participants with either prediabetes or with normal glucose tolerance plus three features of metabolic syndrome were part of the study. SC WAT biopsies were performed before and after 28 days of KDT501 treatment in a clinical research setting. In addition, a cold stimulus was used …

Are Patents Really Limited To 20 Years?, Melody Wriz

Oklahoma Journal of Law and Technology

No abstract provided.

Development Of C5ar-Targeted Nanoparticles For Delivery Of Vaccines, Shailendra Bharadwaj Tallapaka Venkata Sesha

Theses & Dissertations

Since the early attempts of Benjamin Jesty at inducing immunity against smallpox and the pioneering work of Edward Jenner, vaccination has been, and continues to remain, the principal method of protection from diseases. However, most of the successful vaccines have been against pathogens that do not have major mechanisms to evade the immune system. So far, many life-threatening diseases like hepatitis C, HIV infection, malaria etc., have been resistant to existing vaccination strategies. Thus, there is an urgent need to develop new vaccination strategies that can generate long-lived protective immunity against such pathogens.

The purpose of this thesis is to …

Development Of Cxcr4 Inhibitors For Topical Treatment Of Psoriasis, Suthida Boonsith

Theses & Dissertations

Psoriasis is a chronic inflammatory skin disease that is often associated with systemic comorbidities and impaired skin barrier function. There are several treatment options including topical treatment with immunosuppressants, phototherapy, and systemic therapies using small molecules and biological agents. However, none of them can be regarded as a perfect solution due to their toxicity during chronic use. Recently, the CXCR4/SDF-1 axis was found to play an important role in the pathogenesis of psoriasis. AMD3100, a small molecule CXCR4 antagonist can selectively bind to CXCR4 and inhibit skin inflammation, reduce angiogenesis and infiltration of inflammatory cells. Unfortunately, AMD3100 can only be …

Finding Human Proteins That Bind To A Lassa Virus Protein, Maria Alejandra Pardo Ruge, Veronica J. Heintz, Douglas J. Lacount

The Summer Undergraduate Research Fellowship (SURF) Symposium

Viral hemorrhagic fevers are severe illnesses caused by many different viruses. Lassa Virus is one of these important pathogens in Western Africa, causing hemorrhagic fever and eventually death without early medical treatment. There is no vaccine and there is little information on host-pathogen interactions. Therefore, the interaction between viral proteins and host targets is useful to understand Lassa virus’s lifecycle and pathology, and to develop ways to prevent infection. In this project, we study the nucleoprotein of Lassa virus (NP), which has been reported to have anti-interferon (IFN) activity through elimination of double stranded RNA (dsRNA). These features could be …

Discovery Of Novel Tubulin Inhibitors And Selective Survivin Inhibitors For Advanced Melanoma And Total Synthesis Of Bioactive 20s-Hydroxyvitamin D3, Qinghui Wang

Theses and Dissertations (ETD)

According to the statistics from American Cancer Society, the 5-year survival rate for patients with advanced melanoma is as low as 5%. Treatment of advanced melanoma, therefore, represents an unmet medical need. In this dissertation, I will show the effort to develop new generations of bioavailable tubulin inhibitors targeting the colchicine binding site and selective small-molecule survivin inhibitors for treating advanced melanoma. Extensive structure-activity relationship (SAR) studies of lead molecules ABI-231 and UC-112 have been performed.

Chapter 1 will introduce the current situation of advanced or metastatic melanoma, its clinical drug treatments, as well as problems in current drug treatments. …

Tumor-Targeted Delivery Of Sirna Using Fatty Acyl-Cgkrk Peptide Conjugates, Meenakshi Sharma, Naglaa Salem El-Sayed, Hung Do, Keykavous Parang, Rakesh Tiwari, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

Tumor-targeted carriers provide efficient delivery of chemotherapeutic agents to tumor tissue. CGKRK is one of the well-known tumor targeting peptides with significant specificity for angiogenic blood vessels and tumor cells. Here, we designed fatty acyl conjugated CGKRK peptides, based on the hypothesis that hydrophobically-modified CGKRK peptide could enhance cellular permeation and delivery of siRNA targeted to tumor cells for effective silencing of selected proteins. We synthesized six fatty acyl-peptide conjugates, using a diverse chain of saturated and unsaturated fatty acids to study the efficiency of this approach. At peptide:siRNA weight/weight ratio of 10:1 (N/P ≈ 13.6), almost all the peptides …

Cellular And Molecular Targets Of Menthol Actions, Murat Oz, Eslam El Nebrisi, Keun-Hang Susan Yang, Frank Christopher Howarth, Lina T. Al Kury

Mathematics, Physics, and Computer Science Faculty Articles and Research

Menthol belongs to monoterpene class of a structurally diverse group of phytochemicals found in plant-derived essential oils. Menthol is widely used in pharmaceuticals, confectionary, oral hygiene products, pesticides, cosmetics, and as a flavoring agent. In addition, menthol is known to have antioxidant, anti-inflammatory, and analgesic effects. Recently, there has been renewed awareness in comprehending the biological and pharmacological effects of menthol. TRP channels have been demonstrated to mediate the cooling actions ofmenthol. There has been new evidence demonstrating thatmenthol can significantly influence the functional characteristics of a number of different kinds of ligand and voltage-gated ion channels, indicating that at …

Drug-Resistant Epilepsy: Multiple Hypotheses, Few Answers, Fei Tang, Anika M. S. Hartz, Björn Bauer

Pharmaceutical Sciences Faculty Publications

Epilepsy is a common neurological disorder that affects over 70 million people worldwide. Despite the recent introduction of new antiseizure drugs (ASDs), about one-third of patients with epilepsy have seizures refractory to pharmacotherapy. Early identification of patients who will become refractory to ASDs could help direct such patients to appropriate non-pharmacological treatment, but the complexity in the temporal patterns of epilepsy could make such identification difficult. The target hypothesis and transporter hypothesis are the most cited theories trying to explain refractory epilepsy, but neither theory alone fully explains the neurobiological basis of pharmacoresistance. This review summarizes evidence for and against …

Analysis Of The Proposed Tpp-Related Patent Linkage System In Taiwan, Ping-Hsun Chen

Journal of Law and Health

The Trans-Pacific Partnership (TPP) Agreement mandates member states to implement a patent linkage system vested in Article 18.53. To successfully join the TPP Agreement, Taiwan has begun the legislation of a patent linkage system by proposing an amendment for the Pharmaceutical Affairs Act. Article 18.53 requires a member either to adopt a notification mechanism under Paragraph 1 or to stay the issuance of marketing approval under Paragraph 2. But, Taiwan’s proposal includes both measures. Taiwan’s patent linkage system allows a pioneer drug company to register patents claiming (a) a material, (b) a combination or formula, or (c) pharmaceutical use. The …

Efficient Synthesis Of Cn2097 Using In Situ Activation Of Sulfhydryl Group, Shaban Darwish, Keykavous Parang, John Marshall, Dennis J. Goebel, Rakesh Tiwari

Pharmacy Faculty Articles and Research

CN2097 (R₇Cs-sCYK[KTE(β-Ala)]V) is a rationally designed peptidomimetic that shows effectiveness in preclinical models for the treatment of neurological disorders, such as Angelman syndrome, traumatic brain injury (TBI), and stroke. Because of its potential therapeutic activity for the treatment of human CNS disorders, there was an urgent need to develop an efficient strategy for large-scale synthesis of CN2097. The synthesis of CN2097 was accomplished using Fmoc/tBu solid phase chemistry in multiple steps. Two different peptide fragments (activated polyarginine peptide Npys-sCR₇ and CYK[KTE(β-Ala)]V) were synthesized, followed by solution phase coupling in water. Activation of the polyarginine (CR₇) …

Pharmacological Approaches For The Management Of Patients With Moderately Elevated Triglycerides (150-499 Mg/Dl), Michael S. Kelly, Craig Beavers, John D. Bucheit, Evan M. Sisson, Dave L. Dixon

Pharmacy Faculty Articles and Research

Hypertriglyceridemia, defined as serum triglyceride (TG) levels > 150 mg/dL, now affects over one-quarter of the U.S. adult population and is associated with an increased risk of atherosclerotic cardiovascular disease. Available guidelines for managing hypertriglyceridemia vary with respect to triglyceride thresholds and severity of disease. Lifestyle modifications and management of secondary causes (e.g., diabetes) remain the first step in managing hypertriglyceridemia, with pharmacotherapy reserved to reduce the risk of pancreatitis and/or further reduce TG levels. Several classes of lipid-lowering agents are available with variable TG-lowering efficacy. While there is no consensus regarding the choice of initial TG-lowering pharmacotherapy, there is general …

Identification Of A Nucleoside Analog Active Against Adenosine Kinase-Expressing Plasma Cell Malignancies, Utthara Nayar, Jouliana Sadek, Jonathan Reichel, Denise Hernandez-Hopkins, Gunkut Akar, Peter J. Barelli, Michelle A. Sahai, Hufeng Zhou, Jennifer Totonchy, David Jayabalan, Ruben Niesvizky, Ilaria Guasparri, Duane Hassane, Yifang Liu, Shizuko Sei, Robert H. Shoemaker, J. David Warren, Olivier Elemento, Kenneth M. Kaye, Ethel Cesarman

Pharmacy Faculty Articles and Research

Primary effusion lymphoma (PEL) is a largely incurable malignancy of B cell origin with plasmacytic differentiation. Here, we report the identification of a highly effective inhibitor of PEL. This compound, 6-ethylthioinosine (6-ETI), is a nucleoside analog with toxicity to PEL in vitro and in vivo, but not to other lymphoma cell lines tested. We developed and performed resistome analysis, an unbiased approach based on RNA sequencing of resistant subclones, to discover the molecular mechanisms of sensitivity. We found different adenosine kinase–inactivating (ADK-inactivating) alterations in all resistant clones and determined that ADK is required to phosphorylate and activate 6-ETI. Further, we …

Power Dissipation And Power Correlations For A Retreatblade Impeller Under Different Baffling Conditions, Chadakarn Sirasitthichoke

Theses

Glass-lined stirred reactors and tanks are commonly used in the pharmaceutical industry because of their corrosion resistance, ease of cleanliness and minimization of product contamination. Most industrial glass-lined tank reactors are provided with a torispherical tank bottom and a retreat curve impeller with low impeller clearance from the vessel bottom. The power, P, dissipated by the impeller is a critical process parameter to mixing processes to achieve the desired mixing effect, especially since the power per unit volume, P/V, directly controls mass transfer processes and other mixing phenomena. However, little information has been published about the power dissipation and the …

Structure Activity Relationship Studies Of Novel Diarylpentanoid Analogs Targeting The Androgen Receptor In Prostate Cancer Cells, Haili Coffin, Marco Bisoffi

Student Scholar Symposium Abstracts and Posters

The development of prostate cancer (PCa) relies strongly on the activation of the androgen receptor (AR) signaling pathway by its natural ligand dihydrotestosterone. Furthermore, PCa progression to metastatic disease represents oncogene addiction to AR activity. Androgen ablation therapy is thus a mainstay therapy against this disease, but the development of ligand-independent AR activation and persisting AR expression eventually leads to castration resistant PCa (CRPC). Therefore, down-regulation of AR expression in PCa cells may be an effective therapeutic modality. The diarylpentanoid ca27 has previously been shown to down-regulate AR expression by an unknown mechanism of action. The present work represents a …

Translational Pharmacokinetic-Pharmacodynamic Modeling And Simulation In The Development Of Spectinamides, A Novel Class Of Anti-Tuberculosis Agents, Chetan Rathi

Theses and Dissertations (ETD)

New chemotherapeutic agents are urgently needed to control the spread of multidrug-resistant (MDR) and extensively drug-resistant (XDR) forms of tuberculosis, which still remains an important public health challenge globally. Recently, spectinamides have emerged as a novel class of anti-tuberculosis agents that overcomethe native drug efflux. Spectinamides bind to the 30S bacterial ribosomal subunit which interferes with ribosomal translocation, and ultimately results in inhibition of protein synthesis. They have potent in vitro activity against drug resistant Mycobacterium tuberculosis (Mtb), and also demonstrated sustained efficacy in (Mtb)-infected mouse models. Pharmacokinetic (PK)/ pharmacodynamic (PD) analyses play a critical role in identifying …

Cannabinoid Receptor 2 (Cb2) Ligands Downregulate Pro-Inflammatory Markers In Stimulated Primary Human Periodontal Ligament Fibroblasts (Hpdlfs), Ammaar Hasan Abidi

Theses and Dissertations (ETD)

There are approximately 743 million individuals suffering from chronic periodontitis (PD) making it the sixth most prevalent condition worldwide. The affected adult population in the U.S. are nearly 64.7 million and the healthcare costs exceeds $14 billion. Recently, host response to pathogenic infection has been seen critical to the progression of PD and exhibit increase in various inflammatory markers. Marijuana is well known for its recreational usage and is a risk factor for periodontal disease, which is seen as a concern in society for its negative health consequences. However, many medical conditions can benefit from the pharmacological effects of cannabinoids. …

Age-Associated Expression Patterns Of Oatp 1b1 And Oatp 1b3 And Their Effect On The Disposition Of Fexofenadine, Margaret Mary Thomson

Theses and Dissertations (ETD)

As part of the drug disposition process (absorption, distribution, metabolism, excretion), an often overlooked aspect is transport. In order for drugs to be metabolized and excreted from the body they go through the liver or other drug removal organs. For drugs that are polar or are large they must rely upon transport mechanisms to transport them across the biomembranes of the drug removal organs. OATP1B1 and OATP1B3 are transporters on the sinusoidal membrane of the liver which work in concert with the drug metabolizing enzymes as part of the drug removal process. It is known that the development of each …

Synthesis Of 20s-Hydroxyvitamin D3 Analogs And Their 1Α-Hydroxyl Derivatives As Potent Anti-Inflammatory Agents, Zongtao Lin

Theses and Dissertations (ETD)

Rheumatoid arthritis (RA) is one of the autoimmune diseases, and is affecting 2.5 million Americans in total. Among the treatment options of RA, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] is the only steroidal drug used clinically for anti-inflammatory and immune diseases. However, long-term use of 1,25(OH)2D3 (625 µg/day) in human would result in hypercalcemia (toxicity), and 1,25(OH)2D3 has substantial hypercalcemic effects (toxicity) in mice at a dose as low as only 2 µg/kg. Fortunately, during the investigation of novel metabolic pathway of vitamin D3 by cytochrome P450 enzymes, we found 20S-hydroxyvitamin D3 [20S(OH)D3] as a good lead compound. 20S(OH)D3 suppressed disease symptoms at …

Biophysical And Biochemical Screening Approaches For Antimicrobial Drug Discovery Targeting S. Aureus Clpp, Aman Preet Singh

Theses and Dissertations (ETD)

The discovery of antibacterial drugs has been among most significant achievements of mankind in saving millions of lives across the planet from infectious diseases. With rise in resistance to almost all existing chemotypes, the design of next generation novel antibiotics has become much more challenging and difficult. The early 21st century witnessed the advancement of multiple novel chemotypes during golden age of antibiotics however the pace of antibiotic drug discovery has slowed down tremendously, contributing to life threatening antimicrobial discovery void since 1980’s. Therefore the need to develop novel antibiotics with unique mechanism of action to leverage against multi drug …

The Development Of Methods To Account For Physiologic Dynamic Changes And Their Effects On The Pharmacokinetics Of Therapeutic Monoclonal Antibodies And Other Therapeutics, Josiah Thomas Ryman

Theses and Dissertations (ETD)

Physiologic changes in the body can drastically affect the clearance of a medication, and therefore increase the variability in exposure to the medication. Physiologic changes that can have a profound effect on the exposure of a medication can stem from changes CYP enzymes, transport proteins, binding protein expression, organ function, immune reactivity, and health status to name a few; with the focus of this dissertation on the dynamic changes in the ontogeny of MRP2 (an apical liver transport protein) and the dynamic changes caused by an immune response to a therapeutic monoclonal antibody (mAb). Several approaches can be used to …

Biodegradable Polymeric Biomaterials In Different Forms For Long-Acting Contraception And Drug Delivery To The Eye And Brain, Dileep Reddy Janagam

Theses and Dissertations (ETD)

Efficacy of many of the new and existing therapeutics is often hampered by the lack of an effective and compliant method of delivery. Typically, drugs have poor water solubility, short half-lives, and low permeability across the biological membranes. The result is low bioavailability of the drugs at the target site and can cause toxicity and side effects at high doses. Often the conventional dosage forms fail to overcome these limitations. In the recent decades, biodegradable polymeric drug delivery systems have emerged as promising candidates to solve the challenges of poor solubility, low permeability and sustained release owing to the advantages …

Discovery Of Natural Product-Based Antimycobacterial Agents Effective Against Non-Replicating Bacilli, Shajila Siricilla

Theses and Dissertations (ETD)

New antimycobacterial molecules that kill non-replicating Mycobacterium tuberculosis (Mtb) were identified by screening libraries of synthetic natural products. De novo screening of a 400-membered library of aurachin RE analogs resulted in discovery of UT-317 ((R)-20). UT-317 is a selective vitamin K2 biosynthesis (MenA) inhibitor that killed replicating and non-replicating Mtb at 2.31 μg/mL (MIC) and 0.85 μg/mL, respectively. A 50-membered library of capuramycin analogs was evaluated in their enzymatic inhibitory activities against translocase I (MraY/MurX) and prenyl-phosphate-GlcNAc-1-phosphate transferase (WecA). UT-01320 (45) is identified as a selective WecA inhibitor that kills both replicating and non-replicating Mtb at 1.50 μg/mL (MIC) and …

Perbandingan Efektifitas Antara Minyak Atsiri Kulit Batang Kayu Manis (Cinnamomum Burmannii) Dengan Temephos Sebagai Larvasida Aedes Aegypti, Muhamad Rizki Al Kamal, Neneng Syarifah Syafei, Gita Tiara Dewi Nasution

Pharmaceutical Sciences and Research

Dengue fever is a major health issue in the world. Preventive measure with temephos/abate has long been used to combat this problem. Istiana et al reported that there were cases of resistance of Aedes aegypti larvae to temephos in various parts of the world, including Indonesia. Indonesian Cinnamon (Cinnamomum burmannii) has been proven to possess larvacide effect and can be used as an alternative insecticide. This research was meant to compare the larvacide effect of Indonesian cinnamon (Cinnamomum burmannii) essential oil to the larvacide effect of temephos against Aedes aegypti larvae. This research used laboratory experimental design analysis. The total …

Hubungan Kesesuaian Penulisan Resep Dengan Formulariumnasional Terhadap Mutu Pelayanan Pada Pasien Jaminankesehatan Nasional Di Rumah Sakit Umum Di Bandung, Winda Ratna Pratiwi, Angga Prawira Kautsar, Dolih Gozali

Pharmaceutical Sciences and Research

Pharmaceutical service is one of the activities in hospital that support health service quality. One of the factors that can improve quality of pharmaceutical services is prescription services. In the era of National Health Insurance, prescription given to the patients should be based on the National Formulary. If prescriptions did not suit the national formulary, it would influence the services quality on pharmacy unit. The purposes of this study were to determine suitability of prescription outpatients’ national health insurance with national formulary and to determine the relationship of the suitability of prescription with a national formulary to service quality in …

Skrining Dan Evaluasi Aktivitas Kitinase Dari Sembilan Isolat Bakteri Lokal, Baitha Palanggatan Maggadani, Siswa Setyahadi S, Harmita Harmita

Pharmaceutical Sciences and Research

Chitinase is an enzyme that degrades chitin on β-1,4-acetamido-2-deoxy-D-glycoside bound to produce Chitin oligosaccharide or its soluble monomer, N-acetylglucosamine (NAG). Chitinase are usually produced naturally by chitinolytic microorganism that are found in soil or water environment. Chitinase have been widely used for biocontrol agents of plant pests. The product from chitinase hydrolysis can be used as antiinflammatory agent and anti hyperpigmentation. This research was aimed to screen and evaluate the chitinolytic ability of 9 isolate. The best isolate was the one which produced high chitinolytic activity and hydrolyzed chitin into NAG. 9 isolate were examined and BPPTCC-2 was the best …

Kompleks Polielektrolit Kitosan-Xanthan Sebagai Matriks Sediaan Mukoadhesif, Kurnia Sari Setio Putri, Bambang Sulistomo, Silvia Surini

Pharmaceutical Sciences and Research

Mucoadhesive dosage form is a pharmaceutical dosage form with prolonged gastric residence time which can increase bioavailability of drugs. An excipient with suitable swelling and bioadhesive characteristics plays important role to obtain good mucoadhesive dosage form. Our pre-eliminary study showed that chitosan-xanthan gum polyelectrolyte complex (CXPC) in ratio 1:1 exhibit suitable swelling index to be developed as mucoadhesive dosage forms. This research was performed to study CXPC characteristics as matrix for mucoadhesive granules dosage form matrix. In this study CXPC 1:1 was utilized as the matrix in the mucoadhesive granules with drug-CXPC ratio of 1:1, 1:2, and 1:3, using diltiazem …

Parameter Fisikokimia Dan Analisis Kadar Allyl Disulfidedalam Ekstrak Etanol 70% Bawang Putih (Allium Sativum L.)Dengan Perbandingan Daerah Tempat Tumbuh Parameter, Rini Prastiwi, Siska Siska, Nila Marlita

Pharmaceutical Sciences and Research

Garlic (Allium sativum L.) is one of the medicinal plants that has a potential to be developed to become a traditional medicine. Traditional medicinal products and medicinal plants which have good quality are determined by the quality and safety of the extract. One of many factors that can affect the quality is the growing area. This research aimed to compare the value of physicochemical parameters as well as the levels of compounds responsible for pharmacological activity in ethanol 70% extract of garlic obtained from two growing areas, Bogor and Wonosobo. The test results obtained from garlic extract of Bogor were: …