Medicine and Health Sciences Commons^™

Investigation Of Anticoagulation Properties Of Sulfated Glycosaminoglycan Mimetics, Elsamani I. Abdelfadiel

Theses and Dissertations

Abstract

INVESTEGATION OF ANTICOAGULATION PROPERTIES OF SULFATED

GLYCOSAMINOGLYCAN MIMETICS

By Elsamani Ismail Abdelfadiel, MS

A thesis submitted in partial fulfillment of the requirements for the degree of Master of

Science at Virginia Commonwealth University

Virginia Commonwealth University, 2017.

Supervisor: Umesh R Desai

Professor, Department of Medicinal Chemistry

The existence of thrombosis in numerous pathophysiological situations formed a vast necessity for anticoagulation therapy. Thrombin and factor Xa are the only two factors of the entire coagulation cascade that have been major targets for regulation of clotting via the direct and indirect mechanism of inhibition. Our recent discovery of sulfated non-saccharide glycosaminoglycan …

Understanding Over-The-Counter Medication Use And Decision-Making Among Community-Dwelling Us Older Adults: A Mixed-Methods Approach, Yoshita Paliwal

Theses and Dissertations

Introduction

Older adults are regular consumers of over-the-counter (OTC) medications. OTC medications are generally considered safe, and convenient to use without requiring a prescription. However, the safety of an OTC medication and the final health outcome depends in part upon consumers’ perceptions, beliefs, and their decision-making about OTC medication use. The main objectives of this study were: 1) to examine the prevalence and characteristics of OTC medication use among community-dwelling US older adults (65 years and older), 2) to explore older adults’ knowledge, attitudes, beliefs and experiences about OTC medications, and 3) to elicit the OTC medication decision-making process in …

Inhibition Of Oxidative And Conjugative Metabolism Of Buprenorphine Using Generally Recognized As Safe (Gras) Compounds Or Components Of Dietary Supplements, Neha V. Maharao

Theses and Dissertations

This dissertation aimed at developing an inhibitor strategy to improve the oral bioavailability (F_oral) and systemic exposure (AUC_∞) of buprenorphine (BUP) as well as reduce the variability associated with them. Twenty-seven generally recognized as safe (GRAS) compounds or dietary substances were evaluated for their potential to inhibit the oxidative and conjugative metabolism of BUP, using pooled human intestinal and liver microsomes. In both the organs, oxidation appeared to be the major metabolic pathway with a 6 fold (intestine) and 4 fold (liver) higher intrinsic clearance than glucuronidation. Buprenorphine was predicted to show low and variable F …

Design, Synthesis, And Biological Screening Of Selective Mu Opioid Receptor Ligands As Potential Treatments For Opioid Addiction, Samuel Obeng

Theses and Dissertations

Today, more Americans die each year because of drug overdoses than are killed in motor vehicle accidents. In fact, in 2015, more than 33,000 individuals died due to an overdose of heroin or prescription opioids. Sadly, 40-60 % of patients on current opioid addiction treatment medications relapse. Studies have shown that the addiction/abuse liability of opioids are abolished in mu opioid receptor (MOR) knock-out mice; this indicates that the addiction and abuse liability of opioids are mainly mediated through MOR. Utilizing the “message-address concept”, the our laboratory reported a novel non-peptide, reversible MOR selective ligand 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α (isoquinoline-3-carboxamido)morphinan (NAQ). Molecular modeling …

Lung Disposition Model-Based Analyses Of Clinical Pharmacokinetic Profiles For Inhaled Drugs, Anuja Raut

Theses and Dissertations

There has been a desire to accurately interpret the inhaled pharmacokinetic (PK) profiles of drugs in humans to aid successful inhaled drug and product developments. However, challenges are layered, as 1) the drug dose delivered to the lung (DTL) from inhalers is a portion of the formulated dose but rarely determined; 2) lung delivery and regional deposition differ, depending on drug, formulation and inhaler; 3) drugs are not only absorbed from the lung but may also be from the gastrointestinal (GI) tract; and 4) in addition to absorption into the systemic circulation, multiple non-absorptive processes also eliminate drugs from the …

Chemical Probes For Protein Α-N-Terminal Methylation, Brianna D. Mackie

Theses and Dissertations

While protein α-N-terminal methylation has been known for nearly four decades since it was first uncovered on bacteria ribosomal proteins L33, the function of this modification is still not entirely understood. Recent discoveries have demonstrated α-N-terminal methylation is essential to stabilize the interactions between regulator of chromosome condensation 1 (RCC1) and chromatin during mitosis, to localize and enhance the interaction of centromere proteins (CENPs) with chromatin, and to facilitate the recruitment of DNA damage-binding protein 2 (DDB2) to DNA damage foci. Identification of N-terminal methyltransferase 1 (NTMT1) unveiled the eukaryotic methylation writer for protein α-N-termini. In addition, NTMT2 that shares …

Association Of Various Concentrations Of Cat's Claw Herb (Uncaria Tomentosa) On Lymphocyte Proliferation And Nitric Oxide Expression: An In-Vitro Study Of Osteoarthritis, Noha Fadlalddin

Dissertations and Theses @ UNI

Uncaria tomentosa, also known as cat’s claw, is an indigenous herb which originates from the Amazon River basin and has proven to be highly effective via case report and limited epidemiological evaluation in the pallative treatment of a number of inflammatory conditions. The herb is particularly preferred on the American market due to its various uses for healing, which provides the impetus for this research. The herb is being used to treat osteoarthritis and claims have been made for its ability to: enhance the repair of deoxyribonucleic acid (DNA), support joint health and improve immune function, enable normal division of …

Pharmaceutical M&A Activity: Effects On Prices, Innovation, And Competition, Barak D. Richman, Will Mitchell, Elena Vidal, Kevin Schulman

Faculty Scholarship

The rise of blockbuster pharmaceutical acquisitions has prompted fears that unprecedented market concentration will weaken competition. Two of the most prominent concerns focus on the upstream and downstream ends of the pharmaceutical industry: (1) the concern that these mergers will concentrate the market for discovery and will therefore lead to fewer discoveries; and (2) the concern that merging large marketing, sales, and distribution forces will strengthen the hands of select pharmaceutical manufacturers and weaken downstream competition. Having considered potential dynamic effects in the industry and conducted a series of preliminary interviews with knowledgeable observers, though, this Article argues that neither …

Research News. Publications, 2016. Volume 2, University Of Mississippi. School Of Pharmacy, Soumyajit Majumdar

Publications (2015-)

Publications that appeared during the period July 1 through December 31, 2016

Research News. Grants, 2016. Volume 2, University Of Mississippi. School Of Pharmacy, Soumyajit Majumdar

Grants (2015-)

Grants and contracts awarded during July-December 2016

Assessment Of Achieved Systolic Blood Pressure In Newly Treated Hypertensive Patients Aged 60-79 Years Before And After Eighth Joint National Committee Recommendations, Michael S. Kelly, Joseph J. Saseen, Joel C. Marrs

Pharmacy Faculty Articles and Research

Objective:

To determine whether patients who were newly prescribed antihypertensive therapy after the Eighth Joint National Committee (JNC 8) update were treated to a relaxed systolic blood pressure (SBP) goal compared with patients treated before the update.

Methods:

A retrospective cohort study approved by the Colorado Multiple Institutional Review Board. Patients aged 60–79 years, without diabetes or chronic kidney disease (CKD), newly treated for hypertension at a University of Colorado primary care clinics were included. The mean first-achieved and last-stable SBPs of patients newly prescribed antihypertensive medications from 1 January 2012 to 31 December 31 2013 (before cohort) were compared …

Perbandingan Klaim Penyakit Katastropik Peserta Jaminan Kesehatan Nasional Di Provinsi Dki Jakarta Dan Nusa Tenggara Timur, Heniwati Heniwati, Hasbullah Thabrany

Jurnal Ekonomi Kesehatan Indonesia

Several diseases that become catastrophic at the household level include end-stage renal disease, cardiovascular diseases, cancer, thalassemia, and hemophilia. Patients with these diseases benefit significantly from the National Health Insurance (JKN), and these conditions absorb high claim costs from JKN. Special attention is needed to manage these diseases effectively. Disparities in healthcare facilities, specialists, and variations in Case Mix Group (CMG) payment are suspected to be important contributing factors to the variation in JKN fund absorption across provinces. This study uses 2014 claim data from BPJS Kesehatan in Jakarta and East Nusa Tenggara (NTT) provinces to explore the extent of …

Perbandingan Efek Larvasida Minyak Atsiri Daun Cengkeh (Syzygium Aromaticum L.) Varietas Zanzibar Dengan Temephos Terhadap Larva Nyamuk Aedes Aegypti, Ridzmullah Wishnu Pamungkas, Neneng Syarifah Syafei, Arto Yuwono Soeroto

Pharmaceutical Sciences and Research

The use of temephos as larvicides in disease prevention Dengue Hemorrhagic Fever (DHF) in Indonesia has been going on for 40 years. Larviciding very long led the resistance to temephos. Cloves, one of native Indonesia plant contains eugenol that are toxic to the insect’s body. This study aims to examine the effectiveness of Zanzibar clove leaf essential oil compared to temephos in killing the larvae of Aedes aegypti. This study uses experimental laboratory research design. The samples are larvae of Aedes aegypti stage III. The mosquito larvae were classified into six groups, each given a clove leaf essential oil with …

Uji Aktivitas Anti-Inflamasi Minyak Atsiri Daun Kemangi (Ocimum Americanum L.) Pada Tikus Putih Jantan Yang Diinduksi Karagenan, Fadlina Chany Saputri, Rita Zahara

Pharmaceutical Sciences and Research

Kemangi (Ocimum americanum L.) is an aromatic plant that contains citral and known as anti-inflammatory agents. The aim of this study was to determine the anti-inflammatory activity of the essential oil kemangi leaves on carrageenan-induced rat. The male rats were divided into six groups, each consisting of four rats. Group I as negative control was given 0.5% CMC solution, group II as positive control was given diclofenac sodium, group III was given sitral, groups IV, V and VI were given 40 mg/200 g BW, 80 mg/200 g BW, and 160 mg/200 g BW essential oil of Ocimum americanum L., emulsified …

Pengaruh Cara Pengeringan Simplisia Daun Senggani (Melastoma Malabathricum L.) Terhadap Aktivitas Antioksidan Menggunakan Metode Dpph (2,2-Difenil-1-Pikrilhidrazil), Sri Luliana, Nera Umilia Purwanti, Kris Natalia Manihuruk

Pharmaceutical Sciences and Research

Drying is the most important step to keep the compound stability in simplicia. The objective of this research is to know the effect of drying methods on antioxidant activity in Melastoma malabathricum L. The drying methods tested were oven-drying at 40°C, direct sunlight, indirect sunlight, air-drying at ± 25°C and fresh samples as control. Result revealed that the drying methods of simplicia were significant differences for antioxidant activity in Melastoma malabathricum L. (p < 0,05). Drying method that has the highest antioxidant activity was by air-drying at ± 25°C is 54.60 %.

Efektivitas Snedds Ekstrak Kulit Manggis Terhadap Bakteri P. Mirabilis Dan S. Epidermidis Yang Terdapat Pada Ulkus Diabetik, Rafika Sari, Liza Pratiwi, Pratiwi Apridamayanti

Pharmaceutical Sciences and Research

Mangosteen rind possesses the ability to conduct antibacterial activity. Under the development relating to drug delivery system, SNEDDS were known to boost the penetration of active compound. The aim of this research is to compare the effectiveness of the antibacterial activity at both SNEDDS preparation and the ethanol extract of mangosteen rind as the antibacteria against the bacteria that cause diabetic ulcers with the most prevalence whether it was Gram positive or Gram negative bacteria like Proteus mirabilis and Staphylococcus epidermidis. The research started by maceration process with the crude extract as the result continued with the phytochemical screening which …

Analisis Estimasi Biaya Langsung Medis Penderita Rawat Jalan Diabetes Mellitus Tipe 2 Di Rsud Dr. Abdul Aziz Singkawang Tahun 2013, Mursalin Mursalin, Prastuti Soewondo

Jurnal Ekonomi Kesehatan Indonesia

Diabetes mellitus is an epidemic disease that seriously threatens global health. In addition to the high levels of morbidity and mortality, it also causes many countries around the world to spend a significant amount of money on healthcare. This study aims to calculate the direct medical costs and influencing factors of type 2 diabetes mellitus outpatient care. The study was conducted from January to February 2015 at RSUD dr. Abdul Aziz Singkawang in West Kalimantan. The study design used quantitative analysis with secondary data retrospectively collected from 2013, with a sample size of 200. The results of the multivariate analysis …

Malnutrition In Eastern Indonesia: Does Food Access Matter?, Arina Nur Fauziyah

Jurnal Ekonomi Kesehatan Indonesia

Meningkatnya prevalensi kekurangan gizi dan kelebihan berat badan di Indonesia Timur menimbulkan dugaan bahwa keterbatasan akses pangan, baik dari sisi akses ke pasar maupun akses secara ekonomi berpengaruh terhadap beban ganda malnutrisi. Studi ini bertujuan untuk menganalisis pengaruh akses pangan terhadap kekurangan gizi pada balita dan kelebihan berat badan individu dewasa serta kemungkinan terjadinya beban ganda malnutrisi dalam satu rumah tangga di Indonesia Timur. Dengan menggunakan data IFLS East tahun 2012 dan metode estimasi probit serta probit with sample selection, hasil studi menemukan bahwa keterbatasan akses pangan secara ekonomi, dari sisi pendapatan dan harga pangan pokok tidak hanya meningkatkan kemungkinan …

Analisis Pengaruh Dimensi Fraud Triangle Dalam Kebijakan Pencegahan Fraud Terhadap Program Jaminan Kesehatan Nasional Di Rsup Nasional Cipto Mangunkusumo, Hasan Sadikin, Wiku Adisasmito

Jurnal Ekonomi Kesehatan Indonesia

The National Health Insurance (JKN) held by the Social Security Agency (BPJS) Health started to be implemented from 1 Indonesia’s Health Insurance Program in January 2014. The implementation of a national insurance program found the risk. The risk of occurrence of fraud in Indonesia is very high but it is still difficult to identify its risk. This is supported by the lack of awareness of all parties, including patients, providers and insurance companies although such actions exists. Health fraud is a serious threat to the entire world, which led to financial abuse of scarce resources and the negative impact on …

Analisis Pembiayaan Kesehatan Daerah Bersumber Publik: Studi Kasus Di Dinas Kesehatan Kabupaten Bogor Tahun 2012, 2013 Dan 2014, Tuti Handayani, Mardiati Nadjib

Jurnal Ekonomi Kesehatan Indonesia

This study aims to look at the picture of health expenditures in Bogor District Health Office to see the allotment according to the four dimensions of District Health Accounts (DHA) in 2014 to see the trend in 2012 and 2013. This study took data from a secondary data source realization of health spending that was then processed and presented according to the funding source, budget managers, service providers, and programs. The study used a descriptive research design with evaluative approach and was conducted in Bogor District Health Office. Analysis showed that the total health financing in Bogor District Health Department …

Antitumor Activity Of 2,9-Di-Sec-Butyl-1,10-Phenanthroline, Dongsheng Wang, Shifang Peng, Arm R. Amin, Mohammad Aminur Rahman, Sreenivas Nannapaneni, Yuan Liu, Dong M. Shin, Nabil F. Saba, Jack F. Eichler, Zhuo G. Chen

Pharmaceutical Science and Research

The anti-tumor effect of a chelating phen-based ligand 2,9-di-sec-butyl-1,10-phenanthroline (dsBPT) and its combination with cisplatin were examined in both lung and head and neck cancer cell lines and xenograft animal models in this study. The effects of this agent on cell cycle and apoptosis were investigated. Protein markers relevant to these mechanisms were also assessed. We found that the inhibitory effect of dsBPT on lung and head and neck cancer cell growth (IC50 ranged between 0.1–0.2 μM) was 10 times greater than that on normal epithelial cells. dsBPT alone induced autophagy, G1 cell cycle arrest, and apoptosis. Our in vivo …

Current And Evolving Approaches For Improving The Oral Permeability Of Bcs Class Iii Or Analogous Molecules, Vivek S. Dave, Deepak Gupta, Monica Yu, Phong Nguyen, Sheeba Varghese Gupta

Pharmacy Faculty/Staff Publications

The Biopharmaceutics Classification System (BCS) classifies pharmaceutical compounds based on their aqueous solubility and intestinal permeability. The BCS Class III compounds are hydrophilic molecules (high aqueous solubility) with low permeability across the biological membranes. While these compounds are pharmacologically effective, poor absorption due to low permeability becomes the rate-limiting step in achieving adequate bioavailability. Several approaches have been explored and utilized for improving the permeability profiles of these compounds. The approaches include traditional methods such as prodrugs, permeation enhancers, ion-pairing, etc., as well as relatively modern approaches such as nanoencapsulation and nanosizing. The most recent approaches include a combination/hybridization of …

Impact Of Time-Varying Treatment Exposures On The Risk Of Venous Thromboembolism In Multiple Myeloma, Joshua D. Brown, Val R. Adams, Daniela C. Moga

Pharmacy Practice and Science Faculty Publications

Multiple myeloma (MM) has one of the highest risks of venous thromboembolism (VTE) of all cancers due to pathologic changes and treatment-related exposures. This study assessed the one-year incidence of VTE in newly diagnosed MM and to determine the baseline and time-varying treatment-related factors associated with VTE risk in a U.S.-based cohort. MM patients were identified and age, gender, and baseline comorbidities were determined. Treatment-related exposures included thalidomide derivatives (IMIDs), proteasome inhibitors, cytotoxic chemotherapy, steroids, erythropoietin-stimulating agents (ESAs), stem cell transplants (SCT), hospitalizations, infection, and central venous catheters (CVC). Multiple statistical models were used including a baseline competing risks model, …

Advances And Perspectives In Genetics Of Congenital Thyroid Disorders Associated With Thyroglobulin Gene Mutations, Héctor M. Targovnik, Cintia E. Citterio, Sofi Siffo, Carina M. Rivolta

Pharmacy Faculty Articles and Research

Dyshormonogenesis due to thyroglobulin (TG) gene mutations is a rare cause of congenital hypothyroidism with an estimated incidence of approximately 1 in 100,000 newborns. The TG gene is organized in 48 exons, spanning over 270 kb on human chromosome 8q24. The human TG mRNA is 8.5 Kb long and the preprotein monomer is composed of a 19 amino acids signal peptide followed by a 2749 residues polypeptide. Until now, one hundred seventeen deleterious mutations in the human TG gene have been identified and characterized, originating structural changes in the protein that alter the normal protein folding, assembly and …

Chemosensitization Effect Of Sp1017 On Multiple Myeloma, Hangting Hu

Theses & Dissertations

Multiple myeloma (MM) is a hematological malignancy of plasma cells that are predominantly located in bone marrow (BM). Despite recent improvements in MM treatment by introduction of several novel agents includingimmunomodulatory drugs, proteasome inhibitors and the use of the drug combinations, MM remains incurable and almost all patients eventually relapse or become refractory to the current treatment regimens. So the current challenge of MM treatments is to maintain treatment response, prevent relapse and eventually prolong survival.

Here we demonstrated that Pluronic block copolymers ((Pluronic L61: Pluronic F127 = 1:8 w/w, SP1017) significantly increase cytotoxicity of proteasome inhibitors (Bortezomib, BTZ or …

The Effects Orthostatic Hypotension Has On Falls: A Study Done In San Francisco With The Patient Population Of The Veterans Affairs Hospital, Sherry A. Ballard Ms.

Master's Projects and Capstones

The Effects Orthostatic Hypotension has on Falls: A Study Done in San Francisco Represented

Population of the Veterans Affairs Hoapital

The global AIM of this project is to Identify patients that are at risk for Orthostatic Hypotension (OH) with in the first 24 hours of addmission. It was identified that 50% of the falls over the last 4 quarters at the VA were OH related. The patients were not identified as a fall risk and over half of them had fallen multiple times. After performing a nursing survey online, a SWOT analysis, and a Root Cause Analysis using a fishbone …

Comparison Of Outcomes Following A Switch From A Brand To An Authorized Vs. Independent Generic Drug, Richard Hansen, Jingjing Qian, Richard L. Berg, James G. Linneman, Enrique Seoane-Vazquez, Sarah Dutcher, Saeid Raofi, C. David Page, Peggy L. Peissig

Pharmacy Faculty Articles and Research

Authorized generics are identical in formulation to brand drugs, manufactured by the brand company but marketed as a generic. Generics, marketed by generic manufacturers, are required to demonstrate pharmaceutical and bioequivalence to the brand drug, but repetition of clinical trials is not required. This retrospective cohort study compared outcomes for generics and authorized generics, which serves as a generic vs. brand proxy that minimizes bias against generics. For the seven drugs studied between 1999-2014, 5,234 unique patients were on brand drug prior to generic entry and 4,900 (93.6%) switched to a generic. During the 12-months following the brand-to-generic switch, patients …

Polymeric Nanocarriers For Delivery Of Small Molecules And Mirnas For The Treatment Of Liver Fibrosis And Pancreatic Cancer, Virender Kumar

Theses & Dissertations

The aim of this thesis is to develop combination therapy of small molecules and miRNAs for treating liver fibrosis and pancreatic cancer. New amphiphilic biodegradable polymers capable of carrying small hydrophobic molecules and hydrophilic anionic nucleic acids were synthesized, characterized and evaluated in vitro and in vivo liver fibrosis and pancreatic cancer mouse models.

In Chapter 1, an overview of liver fibrosis, current treatments and the role of miRNAs in liver fibrosis as well as the design of their delivery systems is given. Further, a general introduction to pancreatic cancer and role of miRNAs in pancreatic cancer is given. In …

Development Of Cxcr4-Inhibiting Nanoparticles For The Treatment Of Metastatic Cancer, Yan Wang

Theses & Dissertations

Metastasis is the main cause of cancer mortality and morbidity, leading to several million deaths every year. Less than 20% of pancreatic cancer (PC) patients are candidates for surgery due to spread beyond the pancreas. Desmoplasia presents substantial barriers to perfusion, diffusion, and convection of antitumor therapeutics into the PC tissues. We focus on developing novel therapies that regulates tumor microenvironment, chemosensitizing tumor to therapeutics and preventing metastasis.

Gene therapy is emerging as a promising new therapeutic agents for cancer treatment. A targeted, systemic, effective and safe gene delivery system should be developed. CXCR4/SDF-1 axis plays a crucial role in …

Design, Synthesis, And Evaluation Of Aryl Hydantoins And Ureas As Antischistosomal Agents, Chunkai Wang

Theses & Dissertations

Schistosomiasis is a tropical parasitic disease caused by infections with flukes of the genus Schistosoma, affecting as many as 440 million individuals worldwide, with 779 million living at risk of infection. A new drug for schistosomiasis is urgently needed as praziquantel (PZQ) is currently the drug of last resort and the development of resistance cannot be ignored, particularly in view of its large-scale use in many endemic countries. Furthermore, PZQ is active against adult but not juvenile schistosomes; this may be an important factor in the frequently observed treatment ‘failures’ in areas endemic for schistosomiasis.

The introduction of PZQ in …