Chemicals and Drugs Commons^™

April 2018, Randy Curry, Cindy Brooks

RURAL ROCKS

Rural Rocks, the Rural Health Network newsletter by the SWOSU College of Pharmacy

The Predictors Of Juvenile Recidivism: Testimonies Of Adult Students 18 Years And Older Exiting From Alternative Education, La Toshia Palmer

Dissertations

Purpose: The purpose of this descriptive, qualitative study was to identify and describe the importance of the predictors of juvenile recidivism and the effectiveness of efforts to prevent/avoid juvenile recidivism as perceived by previously detained, arrested, convicted, and/or incarcerated adult students 18 years of age and older exiting from alternative education in Northern California. A second purpose was to explore the types of support provided by alternative schools and the perceived importance of the support to avoid recidivism according to adult students 18 years of age and older exiting from alternative education.

Methodology: This qualitative, descriptive research design identified …

Evaluating The Aryl Hydrocarbon Receptor As A Target For Pharmacologic Activity Of Repurposed Drugs, Teofilo Borunda Duque

Pharmaceutical Sciences ETDs

The discovery of new pharmacologic targets is important for the advancement of pharmacotherapy and identification of new indications for current drugs. The aryl hydrocarbon receptor (AHR) is a physiologic sensor of both chemical environmental pollutants and ligands of natural origin. Given the broad spectrum of ligands that activate the AHR and its relationship with toxicology, the AHR is not thought to be a traditional target for pharmacotherapy. However, multiple studies have shown potential for the AHR as a novel pharmacologic target Therefore, identifying less toxic agents that modulate the AHR may elucidate mechanisms for pharmacological targeting of the AHR. The …

Paclitaxel Enhances Oncolytic Potential Of Herpes Simplex Virus Type-1 In Cancer Cells, Misagh Naderi

LSU Master's Theses

Taxanes are spindle poisons that bind to and stabilize microtubules resulting in mitotic arrest. Herpes simplex Typ-1 (HSV-1) virions utilize the microtubular network for intracellular transport during both virus entry and virus egress from infected cells. It has been reported previously that taxanes may synergize with oncolytic herpes simplex viruses in the treatment of experimental prostate and breast tumors in mice. Other reports have indicated that taxanes may inhibit viral replication in infected cells. In this study the previously characterized Oncolytic Herpes Simplex Virus type 1 (OSVP), which was constructed in Kousoulas lab was used in conjugation with paclitaxel (taxol) …

Chemohormonal Therapy In Metastatic Hormone-Sensitive Prostate Cancer: Long-Term Survival Analysis Of The Randomized Phase Iii E3805 Chaarted Trial, Christos E. Kyriakopoulos, Yu-Hui Chen, Michael A. Carducci, Glenn Liu, David F. Jarrard, Noah M. Hahn, Daniel H. Shevrin, Robert Dreicer, Maha Hussain, Mario Eisenberger, Manish Kohli, Elizabeth R. Plimack, Nicholas J. Vogelzang, Joel Picus, Matthew M. Cooney, Jorge A. Garcia, Robert S. Dipaola, Christopher J. Sweeney

Internal Medicine Faculty Publications

Purpose

Docetaxel added to androgen-deprivation therapy (ADT) significantly increases the longevity of some patients with metastatic hormone-sensitive prostate cancer. Herein, we present the outcomes of the CHAARTED (Chemohormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer) trial with more mature follow-up and focus on tumor volume.

Patients and Methods

In this phase III study, 790 patients with metastatic hormone-sensitive prostate cancer were equally randomly assigned to receive either ADT in combination with docetaxel 75 mg/mm² for up to six cycles or ADT alone. The primary end point of the study was overall survival (OS). Additional …

Quality Of Life During Treatment With Chemohormonal Therapy: Analysis Of E3805 Chemohormonal Androgen Ablation Randomized Trial In Prostate Cancer, Alicia K. Morgans, Yu-Hui Chen, Christopher J. Sweeney, David F. Jarrard, Elizabeth R. Plimack, Benjamin A. Gartrell, Michael A. Carducci, Maha Hussain, Jorge A. Garcia, David Cella, Robert S. Dipaola, Linda J. Patrick-Miller

Internal Medicine Faculty Publications

Purpose

Chemohormonal therapy with docetaxel and androgen deprivation therapy (ADT+D) for metastatic hormone-sensitive prostate cancer improves overall survival as compared with androgen deprivation therapy (ADT) alone. We compared the quality of life (QOL) between patients with metastatic hormone-sensitive prostate cancer who were treated with ADT+D and those who were treated with ADT alone.

Methods

Men were randomly assigned to ADT+ D (six cycles) or to ADT alone. QOL was assessed by Functional Assessment of Cancer Therapy-Prostate (FACT-P), FACT-Taxane, Functional Assessment of Chronic Illness Therapy-Fatigue, and the Brief Pain Inventory at baseline and at 3, 6, 9, and 12 months. The …

Antibody-Drug Conjugates For Cancer Therapy: Chemistry To Clinical Implications, Nirnoy Dan, Saini Setua, Vivek K. Kashyap, Sheema Khan, Meena Jaggi, Murali M. Yallapu, Subhash C. Chauhan

School of Medicine Publications

Chemotherapy is one of themajor therapeutic options for cancer treatment. Chemotherapy is often associated with a low therapeutic window due to its poor specificity towards tumor cells/tissues. Antibody-drug conjugate (ADC) technology may provide a potentially new therapeutic solution for cancer treatment. ADC technology uses an antibody-mediated delivery of cytotoxic drugs to the tumors in a targeted manner, while sparing normal cells. Such a targeted approach can improve the tumor-to-normal tissue selectivity and specificity in chemotherapy. Considering its importance in cancer treatment, we aim to review recent efforts for the design and development of ADCs. ADCs are mainly composed of an …

Refrigerated Stability Of Diluted Cisatracurium, Rocuronium, And Vecuronium For Skin Testing After Perioperative Anaphylaxis, Kristen Dinsmore, Bethany Campbell, Timothy Archibald, Greg Mosier, Stacy Brown Phd, Alexei Gonzalez-Estrada Md

Appalachian Student Research Forum

Rationale: The purpose of this study is to investigate the stored stability of dilutions of neuromuscular blocking agents (NMBAs), namely cisatracurium, rocuronium, and vecuronium, for skin prick/intradermal testing.

Methods: Concentrations of NMBAs were monitored by liquid chromatography-mass spectrometry (LC-MS/MS) for a period of 14 days. Dilutions of NMBAs were prepared in saline by factors of 10x, 100x, 1,000x, 10,000x, and 100,000x as sensitivity of the assay allowed. Diluted drug products were stored in a laboratory refrigerator until sampling. On sampling days, aliquots of each dilution were removed and compared to a freshly prepared set of reference dilutions.

Results: The results …

Sirna Knock-Down Of Vav1 In Breast Cancer Cells: Effects On Pi3kinase And Akt, Tajai Sion-Milligan

Student Scholar Showcase

One in eight women in the United States will be diagnosed with breast cancer. Approximately 25-30% of these breast tumors will overexpress Human Epidermal Growth Factor Receptor 2 (HER2), associated with a worse prognosis and decreased survival rate. Stimulation of HER2 results in activation and production of many signaling molecules, ultimately resulting in increased cell division. Two of the downstream molecules activated are PI₃Kinase and, further downstream, the molecule Akt. Typically, overproduction and/or overactivation of PI₃Kinase can lead to oncogenesis. A molecule that may have a significant role in PI₃Kinase formation is VAV1. VAV1 …

Ef-P Post-Translational Modification Has Variable Impact On Polyproline Translation In Bacillus Subtilis, Anne Witzky, Katherine R. Hummels, Rodney Tollerson Ii, Andrei Rajkovic, Lisa A. Jones, Daniel B. Kearns, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Elongation factor P (EF-P) is a ubiquitous translation factor that facilitates translation of polyproline motifs. In order to perform this function, EF-P generally requires posttranslational modification (PTM) on a conserved residue. Although the position of the modification is highly conserved, the structure can vary widely between organisms. In Bacillus subtilis, EF-P is modified at Lys³² with a 5-aminopentanol moiety. Here, we use a forward genetic screen to identify genes involved in 5-aminopentanolylation. Tandem mass spectrometry analysis of the PTM mutant strains indicated that ynbB, gsaB, and ymfI are required for modification and that yaaO, yfkA, and …

Brush-First Synthesis Of Acid-Labile Star-Like Poly(Ethylene Glycol) Nanogels For Drug Delivery Applications, Julian Grundler

Chemistry

The development of multidrug-conjugated polymeric nanoparticles for drug delivery applications promises more effective forms of cancer therapy based on the target-specific, triggered release of therapeutic agents at the tumor site. Discrimination between healthy tissue and tumor cells can be achieved by exploiting the characteristics of the mildly acidic tumor microenvironment. While previous studies showed the potential of acid-responsive polymeric nanoparticles, low drug-loading and failure to release drugs in response to tumor-specific pH conditions remain a challenge in drug delivery and synthetic chemistry. This work presents the synthesis of acid-degradable star-like polymeric nanogels that allow high drug-loading and acid-triggered core degradation …

Do Paraben Derivatives Alter T Cell Immunity?, Hailey Kintz

Spring Presentation of Undergraduate Research

T cells immunity is linked to a complex system of cytokines that determine differentiation of naïve T cells into Th1, Th2, Th17, and Treg cells. Estrogen production or periods of elevated production have been correlated with an anti-inflammatory state in which Th2 and Treg cells are up-regulated. Such responses in the immune system are capable of supporting pre-cancerous activity. We are investigating the tie between the xenoestrogen compounds found in cosmetics, parabens, and their ability to regulate T cell immunity. Testing parabens and paraben derivatives with weaker estrogen receptor association will allow for a better understanding of the interplay between …

Cost-Effectiveness Of Alternative Anticoagulation Strategies For Postoperative Management Of Total Knee Arthroplasty Patients, Savannah R. Smith, Jeffrey Katz, Elena Losina

GW Research Days 2016 - 2020

Background: Anticoagulation is essential for deep vein thrombosis (DVT) and pulmonary embolism (PE) prevention following total knee arthroplasty (TKA). Some research has suggested that longer duration anticoagulation can substantially reduce the risks of DVT and PE; however, in the absence of definitive recommendations, physicians are left weighing the risks of DVT and PE against those of anticoagulation, including gastrointestinal (GI) and central nervous system (CNS) hemorrhage and increased likelihood of prosthetic joint infection (PJI). We conducted a cost-effectiveness analysis to evaluate the benefits and risks of 14- and 35-day therapy with the most commonly prescribed anticoagulants post-TKA.

Background: Anticoagulation is …

Acute Hepatic Failure And Oral Amiodarone, Hani Alhamoud, Sivateja Mandava, Talal Alzahrani

GW Research Days 2016 - 2020

Introduction:

Amiodarone is associated with serious complications such as lung toxicity, thyroid dysfunction, and QT-prolongation. Further, hepatic failure from the intravenous (IV) formulation of amiodarone is described in numerous case reports and case series. Although there are reports of elevated liver enzymes from the oral formulation of amiodarone, to our knowledge, none have definitively identified a case of acute hepatic failure from the oral formulation alone. In this case, we report an instance of acute hepatic failure after increasing the oral amiodarone dosage as well as rapid recovery following cessation of the medication.

Case report:

A 61-year-old male with a …

Onyx Use In Extracranial Pathologies - A Retrospective Case Review, Faezeh Razjouyan, Rishi Sood, Alex Cho, Anthony Venbrux, Shawn Sarin

GW Research Days 2016 - 2020

Purpose:

Onyx is an embolic agent currently FDA approved for neurointerventional procedures such as in the treatment of aneurysms and arteriovenous malformations. Despite its limited indications, the agent's off-label use in the treatment of extracranial pathologies continues to increase. To date, there has not been a single-center study demonstrating a large number of cases demonstrating safe and effective peripheral embolization with Onyx.

Materials:

We performed a retrospective review of all cases that used Onyx between October 2010 and July 2016 at a single tertiary care academic university urban hospital. Institutional review board approval was appropriately obtained. Initial case selection was …

Pupillometric Assessment Of Small Doses Of Opioid In A Pediatric Population, David Strum, Elizabeth Malphrus, Kevin Jackson, Julia Finkel

GW Research Days 2016 - 2020

According to the CDC, opioid prescriptions in the United States have more than tripled from 1999-2014, which has correlated with the staggering increase in opioid-involved drug overdose deaths. This pattern of prescription is thought to be a major contributory factor to the increase in drug overdose in America, as four out of five new heroin users started by misusing prescription painkillers. Providers need the means to objectively monitor analgesic efficacy of treatment in patients with pain to mitigate unnecessary analgesic prescribing.

It is well established that mu opioid agonists like morphine cause miosis, an effect to which tolerance does not …

Cross Talk Between Serum Kisspeptin-Leptin During Assisted Reproduction Techniques, Rehana Rehman, Zehra Jamil, Aqsa Khalid, Syeda Sadia Fatima

Department of Biological & Biomedical Sciences

Background & Objective: Leptin facilitates onset of puberty by impact on hypothalamic Kisspeptin, gonadotropin releasing hormone, follicle stimulating and luteinizing hormone. The link of peripheral Leptin-Kisspeptin in regulating the ovarian and endometrial tissue in relation to adiposity is unknown. Therefore, we wanted to identify Kisspeptin-Leptin association with body mass index (BMI) and success of assisted reproductive treatments (ART) in infertile females.
Methods: A cross sectional study was carried from August 2014 till May 2016 after receiving ethical approval at Australian Concept Infertility Medical Centre, and Aga Khan University. The study group comprised of females with an age range …

Analyzing The Differentiation Among State Medical Marijuana Policies By Examining State Policies & Trends, Richard Furlong

Political Science Theses and Capstones

Support for marijuana has been growing nationwide. This increased support has gained a lot of momentum since the late 1990s when California became the first state to legalize marijuana for medical use by enacting Proposition 215, or the Compassionate Use Act. Since the enactment of Proposition 215, 28 more states and the District of Columbia have legalized marijuana for medicinal use. I look into why states have begun to adopt these laws, and what makes these states differ throughout the country in the timeliness of their actions. I assembled data to examine a variety of state policies to attempt to …

Early Relapse After Autologous Hematopoietic Cell Transplantation Remains A Poor Prognostic Factor In Multiple Myeloma But Outcomes Have Improved Over Time, Shaji K. Kumar, Angela Dispenzieri, Raphael Fraser, Fei Mingwei, Gorgun Akpek, Robert Cornell, Mohamed Kharfan-Dabaja, Cesar Freytes, Shahrukh Hashmi, Gerhard C. Hildebrandt, Leona Holmberg, Robert Kyle, Hillard Lazarus, Cindy Lee, Jospeh Mikhael, Taiga Nishihori, Jason Tay, Saad Usmani, David Vesole, Ravi Vij, Baldeep Wirk, Amrita Krishnan, Cristina Gasparetto, Tomer Mark, Yago Nieto, Parameswaran Hari, Anita D'Souza

Internal Medicine Faculty Publications

Duration of initial disease response remains a strong prognostic factor in multiple myeloma (MM) particularly for upfront autologous hematopoietic cell transplant (AHCT) recipients. We hypothesized that new drug classes and combinations employed prior to AHCT as well as after post-AHCT relapse may have changed the natural history of MM in this population. We analyzed the Center for International Blood and Marrow Transplant Research database to track overall survival (OS) of MM patients receiving single AHCT within 12 months after diagnosis (N=3256) and relapsing early post-AHCT (< 24 months), and to identify factors predicting for early vs late relapses (24−48 months post-AHCT). Over three periods (2001–2004, 2005–2008, 2009–2013), patient characteristics were balanced except for lower proportion of Stage III, higher likelihood of one induction therapy with novel triplets and higher rates of planned post-AHCT maintenance over time. The proportion of patients relapsing early was stable over time at 35–38%. Factors reducing risk of early relapse included lower stage, chemosensitivity, transplant after 2008 and post-AHCT maintenance. Shorter post-relapse OS was associated with early relapse, IgA MM, Karnofsky < 90, stage III, > 1 line of induction and lack of maintenance. Post-AHCT early relapse remains …

Chemiluminescent Agents For In Vivo Imaging, Jian Cao

Chemistry Theses and Dissertations

Chemiluminescence is the light production directly from a highly exothermic chemical reaction by generating electronically excited species, and the light will be generated upon relaxation to the ground state. We utilize this light as the readout to construct imaging agents for reactive species. Chemiluminescence as an imaging modality has many advantages compared with current widely used imaging modalities, such as fluorescence and bioluminescence. The main advantages are the elimination of extraneous light excitation or genetic modification, which are required for fluorescence and bioluminescence imaging. Therefore, chemiluminescence as a imaging modality holds great potential for in vivo imaging.

In this dissertation, …