Pharmacy and Pharmaceutical Sciences Commons^™

Rituximab Treatment For Antibody-Mediated Rejection (Amr) Following Heart And Kidney Transplant, Laura Falconieri, Ba, Pharmd, Cheryl A. Abbas, Pharmd

Pharmacy Presentations, Posters, and Grand Rounds

Background

Antibody Mediated Rejection (AMR)1,2

• Rejection that occurs due to antibodies against donor-specific antigen (DSA)

– Antibodies activate complement system

– Leads to cell death and tissue necrosis

• Risk Factors

– Pregnancy

– Blood transfusions

– Prior transplantation

• Types of AMR

– Hyperacute

• Occurs within minutes of graft transplantation causing death of the graft

• Due to pre-formed antibodies present in high titers

• Rarely occurs now due to universal cross-matching

– Acute

• Occurs within a few days of transplantation causing graft dysfunction

• Due to pre-formed antibodies or antibodies that develop de novo after …

Use Of Apheresis And Insulin For Hypertriglyceridemia-Induced Pancreatitis And Diabetic Ketoacidosis, Drew Kirk, Pharmd, Cara Mcdaniel, Pharmd, Bcps, Rohit A. Moghe, Pharmd, Msph, Cde

Pharmacy Presentations, Posters, and Grand Rounds

CLINICAL RELEVANCE

• Acute pancreatitis (AP) is a common gastrointestinal disease that may result in multiple organ failure and death¹

– Gallstones & alcohol are the most common causes of AP¹

– Hypertriglyceridemia (HTG) causes 1-4% of cases, and should be suspected if triglycerides (TG) are > 1,000 mg/dL in the absence of gallstones or history of significant alcohol use¹

– Clinical management of hypertriglyceridemia-induced pancreatitis (HTGP) is based primarily on anecdotal evidence and case reports

• Concurrent diabetic ketoacidosis (DKA) and AP have been described in the literature

– DKA may be a risk factor for AP, but it …

Increased Levels Of Plasma Soluble Sema4d In Patients With Heart Failure., Qiongyu Lu, Ningzheng Dong, Qi Wang, Wenxiu Yi, Yuxin Wang, Shengjie Zhang, Haibo Gu, Xin Zhao, Xiaorong Tang, Boquan Jin, Qingyu Wu, Lawrence F Brass, Li Zhu

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Semaphorin 4D (Sema4D/CD100) is a 150-kDa transmembrane glycoprotein expressed by platelets and T-cells. When these cells are activated, Sema4D is cleaved proteolytically, generating a biologically active 120-kDa fragment (soluble Sema4D) capable of targeting receptors on platelets, B-cells, endothelial cells and tumor cells. However, its plasma levels and significance in heart failure (HF) have not been reported. In this study, we established an ELISA and detected soluble Sema4D in human plasma. In healthy controls, plasma Sema4D levels were higher in men than women (5.15±3.30 ng/mL, n = 63, vs. 4.19±2.39 ng/mL, n = 63, P

Investigating Key Post-Pks Enzymes From Gilvocarcin Biosynthetic Pathway, Nidhi Tibrewal

Theses and Dissertations--Pharmacy

Gilvocarcin V (GV) belongs to the angucycline class of antibiotics that possesses remarkable anticancer and antibacterial activities with low toxicity. Gilvocarcin exhibits its light induced anticancer activity by mediating crosslinking between DNA and histone H3. When photo-activated by near-UV light, the C8 vinyl group forms a [2+2] cycloadduct with thymine residues of double stranded DNA. _D-fucofuranose is considered essential for histone H3 interactions. However, the poor water solubility has rendered it difficult to develop gilvocarcin as a drug. We aim to design novel gilvocarcin analogues with improved pharmaceutical properties through chemo-enzymatic synthesis and mutasynthesis. Previous studies have characterized many …

Phase Composition Control Of Calcium Phosphate Nanoparticles For Tunable Drug Delivery Kinetics And Treatment Of Osteomyelitis. Part 2: Antibacterial And Osteoblastic Response, Vuk Uskoković, Tejal A. Dasai

Pharmacy Faculty Articles and Research

Osteomyelitis has been traditionally treated by the combination of long-term antibiotic therapies and surgical removal of diseased tissue. The multifunctional material was developed in this study with the aim to improve this therapeutic approach by: (a) enabling locally delivered and sustained release of antibiotics at a tunable rate, so as to eliminate the need for repetitive administration of systemically distributed antibiotics; and (b) controllably dissolving itself, so as to promote natural remineralization of the portion of bone lost to disease. We report hereby on the effect of the previously synthesized calcium phosphates (CAPs) with tunable solubilities and drug release time …

Ultrasonication Assisted Layer-By-Layer Technology For The Preparation Of Multi-Functional Anticancer Drugs Paclitaxel And Lapatinib, Xingcai Zhang

Doctoral Dissertations

In this dissertation, ultrasonication assisted Layer-by-Layer (LbL) technology for the preparation of multifunctional poorly water-soluble anticancer drug nanoparticles, paclitaxel and lapatinib, has been developed. Many FDA approved drugs are very low soluble in water; therefore, it is very difficult to load and control their release and targeting efficiently, which greatly confines their application. The development of this method will pave the way for the development and application of those low soluble anticancer drugs.

In the first part of this dissertation, the first approach for powerful ultrasonication, the top-down approach (sonicating bulk drug crystals in polyelectrolyte solution), was successfully applied for …

Testosterone Use And Effects, Brandon Mills

Natural Sciences Student Research Presentations

Summarizes the chemical make-up, medical applications and side effects for the steroidal hormone Testosterone. This is a project for the Natural Sciences Poster Session at Parkland College.

Acute Coronary Syndromes: Current Treatment Guidelines And Updates, Bernard Lau, Michael Lee, Thien Tran, Laura Tsu

Pharmacy Faculty Articles and Research

This home-study CPE activity has been developed to educate pharmacists on acute coronary syndrome (ACS) and its medical management.

What Evidence Is Available On Aldosterone Antagonists For Use In Heart Failure With Preserved Ejection Fraction?, Vivian Loo, Laura Tsu

Pharmacy Faculty Articles and Research

This drug information question and answer sheet discusses the use of aldosterone antagonists for use in heart failure with preserved ejection fraction.

Calcium Phosphate Nanoparticles: A Future Therapeutic Platform For The Treatment Of Osteomyelitis?, Tejal A. Dasai, Vuk Uskoković

Pharmacy Faculty Articles and Research

No abstract provided.

Chikungunya Virus Infection Results In Higher And Persistent Viral Replication In Aged Rhesus Macaques Due To Defects In Anti-Viral Immunity, Ilhem Messaoudi, Jennifer Totonchy, Thomas Totonchy, Craig N. Kreklywich, Kristen Haberthur, Laura Springgay, James D. Brien, Michael S. Diamond, Victor R. Defilippis, Daniel N. Streblow

Pharmacy Faculty Articles and Research

Chikungunya virus (CHIKV) is a re-emerging mosquito-borne Alphavirus that causes a clinical disease involving fever, myalgia, nausea and rash. The distinguishing feature of CHIKV infection is the severe debilitating poly-arthralgia that may persist for several months after viral clearance. Since its re-emergence in 2004, CHIKV has spread from the Indian Ocean region to new locations including metropolitan Europe, Japan, and even the United States. The risk of importing CHIKV to new areas of the world is increasing due to high levels of viremia in infected individuals as well as the recent adaptation of the virus to the mosquito species Aedes …

Aberrant Proliferation In Cxcr7+ Endothelial Cells Via Degradation Of The Retinoblastoma Protein, Jennifer Totonchy, Jessica M. Osborn, Sara Botto, Lisa Clepper, Ashlee V. Moses

Pharmacy Faculty Articles and Research

Angiogenesis is a critical factor in the growth and dissemination of solid tumors. Indeed, tumor vasculature is abnormal and contributes to the development and spread of malignancies by creating a hostile microenvironment. The alternative SDF-1/CXCL12 receptor, CXCR7, is frequently and specifically expressed in tumor-associated vessels. In this study, we examine the role of endothelium-expressed CXCR7 in tumor vascular dysfunction by specifically examining the contribution of CXCR7 to endothelial cell (EC) proliferation. We demonstrate that CXCR7 expression is sufficient to drive post-confluent growth in EC cultures. Further, we provide a novel mechanism for CXCR7-mediated proliferation via proteasomal degradation of the tumor …

Corneal Gene Therapy: Basic Science And Translational Perspective, Rajiv R. Mohan, Jason T. Rodier, Ajay Sharma

Pharmacy Faculty Articles and Research

Corneal blindness is the third leading cause of blindness worldwide. Gene therapy is an emerging technology for corneal blindness due to the accessibility and immune-privileged nature of the cornea, ease of vector administration and visual monitoring, and ability to perform frequent noninvasive corneal assessment. Vision restoration by gene therapy is contingent upon vector and mode of therapeutic gene introduction into targeted cells/tissues. Numerous efficacious vectors, delivery techniques, and approaches have evolved in last decade for developing gene-based interventions for corneal diseases. Maximizing the potential benefits of gene therapy requires efficient and sustained therapeutic gene expression in target cells, low toxicity, …

Bmp7 Gene Transfer Via Gold Nanoparticles Into Stroma Inhibits Corneal Fibrosis In Vivo, Ashish Tandon, Ajay Sharma, Jason T. Rodier, Alexander M. Klibanov, Frank G. Rieger, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

This study examined the effects of BMP7 gene transfer on corneal wound healing and fibrosis inhibition in vivo using a rabbit model. Corneal haze in rabbits was produced with the excimer laser performing -9 diopters photorefractive keratectomy. BMP7 gene was introduced into rabbit keratocytes by polyethylimine-conjugated gold nanoparticles (PEI2- GNPs) transfection solution single 5-minute topical application on the eye. Corneal haze and ocular health in live animals was gauged with stereo- and slit-lamp biomicroscopy. The levels of fibrosis [a-smooth muscle actin (aSMA), F-actin and fibronectin], immune reaction (CD11b and F4/80), keratocyte apoptosis (TUNEL), calcification (alizarin red, vonKossa and osteocalcin), and …

Fine Tuning A Well-Oiled Machine: Influence Of Nk1.1 And Nkg2d On Nkt Cell Development And Function, Sunil K. Joshi, Mark L. Lang

Bioelectrics Publications

Natural killer T cells (NKT) represent a group of CD1d-restricted T-lineage cells that provide a functional interface between innate and adaptive immune responses in infectious disease, cancer, allergy and autoimmunity. There have been remarkable advances in understanding the molecular events that underpin NKT development in the thymus and in the complex array of functions in the periphery. Most functional studies have focused on activation of T cell antigen receptors expressed by NKT cells and their responses to CD1d presentation of glycolipid and related antigens. Receiving less attention has been several molecules that are hallmarks of Natural Killer (NK) cells, but …

Characterization Of Different Hydrophilic Polymers And Their Applicability In Hot Melt Extrusion Technology, Sindhuri Maddineni

Electronic Theses and Dissertations

Research in the pharmaceutical field involves investigation of a new drug, delivery route, a delivery system, a technology to design the delivery system, or a combination thereof. Scientists have explored several delivery routes such as oral, pulmonary, nasal, injection/implant, transdermal/dermal, transmucosal etc. for their potential to transport a variety of small and large drug molecules. In the present research work, oral route, a widely accepted route of administration, for the delivery of products with a major market share, has been considered for the delivery of poorly soluble actives. The use of appropriate carrier matrices (polymers) and excipients help in incorporating …

Effect Of 2-Deoxyglucose On Colorectal Cancer Cell Lines, Alex Olinger, Pratik Muley, Hemachand Tummala

The Journal of Undergraduate Research

The third leading cause of cancer deaths in the U.S. is colon cancer. The major disadvantage of cancer chemotherapy is its non-selective toxicity to healthy cells at the therapeutic doses. A possible target selective for cancer cells is their dependence on glycolysis for cellular energy. 2-deoxyglucose (2-DG) is a glycolytic inhibitor that has been shown to be safe in both animals and humans. The molecular mechanisms for the anticancer effect of 2-DG cannot be explained solely by its glycolytic inhibition. In this manuscript we studied the effect of 2-DG on colon cancer cells and its possible molecular mechanism. Colon cancer …

New Oral Anticoagulants In The Treatment Of Pulmonary Embolism: Efficacy, Bleeding Risk, And Monitoring, Kelly M. Rudd, Elizabeth Phillips

Pharmacy Faculty/Staff Publications

Anticoagulation therapy is mandatory in patients with pulmonary embolism to prevent significant morbidity and mortality. The mainstay of therapy has been vitamin-K antagonist therapy bridged with parenteral anticoagulants. The recent approval of new oral anticoagulants (NOACs: apixaban, dabigatran, and rivaroxaban) has generated significant interest in their role in managing venous thromboembolism, especially pulmonary embolism due to their improved pharmacokinetic and pharmacodynamic profiles, predictable anticoagulant response, and lack of required efficacy monitoring. This paper addresses the available literature, on-going clinical trials, highlights critical points, and discusses potential advantages and disadvantages of the new oral anticoagulants in patients with pulmonary embolism.

The Design, Synthesis, And Biological Evaluation Of Aplysinopsin Analogs As Potential Neuromodulators, Kevin Lewellyn

Electronic Theses and Dissertations

Aplysinopsins are tryptophan-derived natural products that have been isolated from a variety of marine organisms and have been shown to possess a range of biological activities. Initial synthesis of a library of 50 aplysinopsin analogs revealed that of the 12 serotonin receptor subtypes and 34 other CNS receptors, aplysinopsin analogs shoa high affinity for the 5-HT2B and 5-HT2C receptor subtypes, with selectivity for 5-HT2B over 5-HT2C. Bromination at C-4 and C-5 of the indole ring resulted in greater binding affinities, with Ki's as low as 35 nM. In addition, biological evaluation of the MAO-A and MAO-B inhibitory activities of these …

Synthesis Of Natural Product-Based Sphingosine Derivatives, Zarana Daksh Chauhan

Electronic Theses and Dissertations

Marine sponges represent an excellent source of sphingolipids and their metabolites, especially sphingosine-1-phosphate (S1P). S1P plays an important role in cell differentiation, survival, proliferation and the immune response. The enzyme sphingosine kinase (SK) is critical for the phosphorylation of sphingosine to S1P and has been examined as a druggable target for the treatment of hyper-proliferative diseases, inflammation, cancer and other pathological conditions. Natural products that consist of an azetidine ring represents an interesting class of conformationally constrained scaffolds that may serve as effective lead compounds for SK inhibitor development. Hence, the goal of this thesis research was to synthesize natural-product …