Chemicals and Drugs Commons^™

Descriptive Study Of Prescriptions For Opioids From A Suburban Academic Emergency Department Before New York's I-Stop Act., Lyncean Ung, Ronald Dvorkin, Steven Sattler, David P. Yens

The School of Health Sciences Publications and Research

Introduction: Controlled prescription opioid use is perceived as a national problem attributed to all specialties. Our objective was to provide a descriptive analysis of prescriptions written for controlled opioids from a database of emergency department (ED) visits prior to the enactment of the I-STOP law, which requires New York prescribers to consult the Prescription Monitoring Program (PMP) prior to prescribing Schedule II, III, and IV controlled substances for prescriptions of greater than five days duration.

Methods: We conducted a retrospective medical record review of patients 21 years of age and older, who presented to the ED between July …

Nanotechnology Solutions For Global Water Challenges, Aine Whelan, Niall B. Mcguinness, Mary Garvey, Honey John, Chun Zao, Geshan Zhang, Dionysios D. Dionysiou, J. Anthony Byrne, Suresh C. Pillai

Books/Book chapters

The lack of clean and safe drinking water is responsible for more deaths than war, terrorism and weapons of mass destruction combined. This suggests contaminated water poses a significant threat to human health and welfare. In addition, standard water disinfection approaches such as sedimentation, filtration, and chemical or biological degradation are not fully capable of destroying emerging contaminants (e.g. pesticides, pharmaceutical waste products) or certain types of bacteria (e.g. Cryptosporidium parvum). Nanomaterials and nanotechnology based devices can potentially be employed to solve the challenges posed by various contaminants and microorganisms. Nanomaterials of different shapes, namely nanoparticles, nanotubes, nanowires and fibers …

In Vitro Evaluation Of The Cytotoxicity Of A Folate-Modified Β-Cyclodextrin As A New Anti-Cancer Drug Delivery System, Zlata Tofzikovskaya, Alan Casey, Orla L. Howe, Christine O'Connor, Mary Mcnamara

Articles

Many chemotherapeutic drugs are therapeutically non-selective and do not distinguish between healthy cells and tumour cells which can result in severe side effects and toxicity. Drug delivery systems can be used to target specific cells and therefore may eliminate many of the side effects, increasing drug efficiency and efficacy, and controlling drug release. One possible strategy for targeted drug delivery is to use unique molecular markers such as folate receptors in cancer cells. In this work the cytotoxicity of a novel cyclodextrin-folate conjugate, 6-deoxy-6-[(1-(-2amino)ethylamino)folate-β-cyclodextrin (CDEnFA) was studied using the MTT assay and the MCF-7 (Breast), HeLa (Cervical), A549 (Lung cancer) …

Mdivi-1, A Mitochondrial Division Inhibitor, Exerts Cardioprotective Effects In Myocardial Ischemia/Reperfusion (Mi/R) When Given At Reperfusion, Devon P. Stutzman

PCOM Biomedical Studies Student Scholarship

Acute myocardial infarction (MI) remains a leading cause of morbidity and mortality worldwide. Accompanying MI is myocardial ischemia/reperfusion (MI/R) injury, which results in cardiac contractile dysfunction and additional myocardial cell death. MI/R injury is initiated in part by mitochondrial-derived reactive oxygen species due to mitochondrial membrane potential collapse and uncoupling of the electron transport chain, which may be due to mitochondrial fission in MI/R. Mitochondrial fission is in turn associated with shortening/fragmentation of mitochondria, decreased ATP production, and is thought to promote cardiac contractile dysfunction and post-reperfused cardiomyocyte loss, leading to increased infarct size. Therefore, inhibiting mitochondrial fission may be …

Analysis Of Humira, Electro-Acupuncture, And Pulsatile Dry Cupping On Reducing Joint Inflammation In Patients With Rheumatoid Arthritis, Natalie Noll

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Humira, an anti-TNF drug aimed at decreasing inflammation in Rheumatoid Arthritis patients, can cause skin diseases from rashes to skin cancer. Humira works by blocking the chemical receptor RANKL which inhibits the production of osteoclasts. Osteoclasts are cells that attack and eat bone and cartilage therefore an inhibitory mechanism would cause inflammation.. By analyzing Humira’s effect on the human body, Humira can be compared to other treatments such as electro-acupuncture and pulsatile dry cupping to determine the viability of these alternative treatment methods in regards to their abilities to decrease inflammation in Rheumatoid Arthritis patients through blocking RANKL. An analysis …

Engineering Approaches For Suppressing Deleterious Host Responses To Medical Implants, Connor Mccarthy

Dissertations, Master's Theses and Master's Reports

Small diameter (< 6 mm) vascular grafts suffer from serious deleterious effects not encountered with their larger diameter relatives, leading to premature graft failure through restenosis. Platelet activation, inflammation, and smooth muscle cell proliferation are leading contributors to thrombosis and neointimal hyperplasia, both contributors to the progression of restenosis. It may be possible to suppress negative biological responses to vascular implants through the modification of surface properties and incorporation of drug release into blood contacting materials. In this work, bioengineering approaches are presented to improve the biocompatibility of small diameter vascular grafts.

We demonstrate a novel engineering approach for incorporating natural, decollagenized elastin matrices into PEU 1074A reinforced vascular grafts through spray-coating and electrospinning processes in a manner that retains elastin’s excellent blood contacting properties. A vascular construct with excellent mechanical and surgical handling properties demonstrating the suppression of neointimal hyperplasia is presented after 21 days in vivo.

Nitric oxide (NO) has been investigated over the past several decades due to its platelet, inflammation, and smooth muscle cell suppressing effects; and if appropriately delivered, could positively mediate the contributors to restenosis. Here, we characterize a novel macrocyclic NO …

Scientific And Regulatory Policy Committee (Srpc) Review*: Interpretation And Use Of Cell Proliferation Data In Cancer Risk Assessment, Charles E. Wood, Renee R. Hukkanen, Radhakrisha Sura, David Jacobson-Kram, Thomas Nolte, Marielle Odin, Samuel M. Cohen

United States Food and Drug Administration: Publications

Increased cell proliferation is a central key event in the mode of action for many non-genotoxic carcinogens, and quantitative cell proliferation data play an important role in the cancer risk assessment of many pharmaceutical and environmental compounds. Currently, there is limited unified information on assay standards, reference values, targeted applications, study design issues, and quality control considerations for proliferation data. Here, we review issues in measuring cell proliferation indices, considerations for targeted studies, and applications within current risk assessment frameworks. As the regulatory environment moves toward more prospective evaluations based on quantitative pathway-based models, standardiza- tion of proliferation assays will …

Design, Synthesis, Antiviral Activity, And Pre-Formulation Development Of Poly-Larginine- Fatty Acyl Derivatives Of Nucleoside Reverse Transcriptase Inhibitors, Bhanu P. Pemmaraju, Swapnil Malekar, Hitesh K. Agarwal, Rakesh Tiwari, Donghoon Oh, Gustavo F. Doncel, David R. Worthen, Keykavous Parang

Pharmacy Faculty Articles and Research

The objective of this work was to design conjugates of anti-HIV nucleosides conjugated with fatty acids and cell-penetrating poly-L-arginine (polyArg) peptides. Three conjugates of polyArg cell-penetrating peptides with fatty acyl derivatives of alovudine (FLT), lamivudine (3TC), and emtricitabine (FTC) were synthesized. In general, the compounds exhibited anti-HIV activity against X4 and R5 cell-free virus with EC50 values of 1.5–16.6 μM. FLT-CO-(CH2)12-CO-(Arg)7 exhibited EC50 values of 2.9 μM and 3.1 μM against X4 and R5 cell-free virus, respectively. The FLT conjugate was selected for further preformulation studies by determination of solution state degradation and lipid solubility. The compound was found to …

Mechanisms, Potential Therapies, And The Role Of Tgf-Β In The Formation Of Scars, Isaac Traube

The Science Journal of the Lander College of Arts and Sciences

Scarring is the inevitable outcome of wound healing. This review looks at some of the underlying mechanisms of this complex process with the aim of identifying targets for therapeutic manipulation that could result in reduced scarring or even scarless wound repair. Fetal wounds are shown to heal without scars primarily due to low levels of TGF-β1 and TGF-β2 and high levels of TGF-β3 as compared to adult wounds which heal with scars. Abnormal excessive scarring in keloid and hypertrophic scars are also attributed to TGF-β. Clinical manipulation of TGF-β ratios showed promise as a therapeutic means of controlling scar formation. …

Is There A Link Between Saturated Fat Intake And Alzheimer’S Disease?, Justin Konig

The Science Journal of the Lander College of Arts and Sciences

Alzheimer’s disease is a neurodegenerative disease that causes dementia and ultimately death. Currently, there is no treatment available for this disease. The aging of the population will only increase the incidence of Alzheimer’s disease, making it ever more important to find an effective method of prevention. Dietary intervention is a practical and affordable method of intervention. The brain is a fat rich organ, and dietary fats are critical for proper development of the brain. A literature review was conducted to determine whether there is a link between saturated fat intake and Alzheimer’s disease. According to the literature reviewed, saturated fat …

Regulation Of Ghrelin: A Possible Treatment Option For Obesity And Diabetes, Sarah Picciotto

The Science Journal of the Lander College of Arts and Sciences

Obesity is a mounting problem in America today. One major concern about obesity is that it is a risk factor for type 2 diabetes, a disease that impairs insulin sensitivity and secretion. This interferes with blood glucose levels and can cause hyperglycemia, which is when there is too much circulating glucose in the blood. Ghrelin, an amino acid peptide responsible for appetite stimulation and energy balance, plays a direct role in insulin secretion and glucose metabolism. In many experiments, elevated ghrelin levels are associated with decreased insulin secretion from pancreatic islet cells. Although ghrelin concentration is decreased in obese individuals …

Target-Directed Biosynthetic Evolution: Redirecting Plant Evolution To Genomically Optimize A Plant’S Pharmacological Profile, Dustin Paul Brown

Theses and Dissertations--Neuroscience

The dissertation describes a novel method for plant drug discovery based on mutation and selection of plant cells. Despite the industry focus on chemical synthesis, plants remain a source of potent and complex bioactive metabolites. Many of these have evolved as defensive compounds targeted on key proteins in the CNS of herbivorous insects, for example the insect dopamine transporter (DAT). Because of homology with the human DAT protein some of these metabolites have high abuse potential, but others may be valuable in treating drug dependence. This dissertation redirects the evolution of a native Lobelia species toward metabolites with greater activity …

Chemoenzymatic Studies To Enhance The Chemical Space Of Natural Products, Jhong-Min Chen

Theses and Dissertations--Pharmacy

Natural products provide some of the most potent anticancer agents and offer a template for new drug design or improvement with the advantage of an enormous chemical space. The overall goal of this thesis research is to enhance the chemical space of two natural products in order to generate novel drugs with better in vivo bioactivities than the original natural products.

Polycarcin V (PV) is a gilvocarcin-type antitumor agent with similar structure and comparable bioactivity with the principle compound of this group, gilvocarcin V (GV). Modest modifications of the polyketide-derived tetracyclic core of GV had been accomplished, but the most …

Use Of Swine Small Intestine Submucosa As A Dermal Suture, Paige E. Black

PCOM Biomedical Studies Student Scholarship

The purpose of this preliminary study is to determine if swine small intestine submucosa (SIS) can be used to create a suture that will perform comparably to commercially available chromic gut sutures when placed into a wound in rat dermis. This study is part of an ongoing collaboration that has explored SIS as a biologic scaffold in various tissues and surgical procedures. In this study, eight Sprague-dawley rats were divided into two groups, each receiving a full thickness skin wound between the scapula, made by a 5mm biopsy punch. The wound was then closed with commercially available chromic gut suture, …

Sharp Rna Recognition Motif Optimizations, Extensions, And Mutations For Use In 2d And 3d Nmr Experiments, Shaun M. Christie

Williams Honors College, Honors Research Projects

SMRT/HDAC Associated Repressor Protein interacts with the long noncoding RNA, produced by SRA, by binding at the RRMs. Three projects were done to prepare the truncated proteins for use in 2D and 3D NMR experiments. The first focuses on RRM 3 and its optimization during the purification process. The second focuses on RRM 2-4, which was found to be missing two alpha helices that may be important for protein stability. These helices can also interact with RRM 3 as well due to the tight association of RRMs 3 and 4. The two step PCR extension of RRM 2-4 was assumed …

Utilization Of Placebo Response In Double-Blind Psychopharmacological Studies, Contextual Perspective, Margarita Olegovna Ashirova

Antioch University Dissertations & Theses

Placebo response has been an elusive phenomenon in the fields of medicine, medical research, and psychology. Even though it has been heavily utilized as a comparator treatment in double-blind psychopharmacological studies, the reliable definition and consistent understanding of placebo response are missing. In this contextual exploration, I outlined the state of current placebo response research and variable rates of placebo response reported in double-blind studies. I identified the gap in the literature—lack of consistent understanding of placebo response—that has led to a waste of resources by the psychopharmacological research industry. Further, I compared and contrasted the current inconsistent Western medical …

Drug Interactions With Glutaredoxin Orthologues, Kahlilah R. Napper, Thomas C. Leeper, Ram Khattri, Daniel Morris, Caroline Davis

Williams Honors College, Honors Research Projects

Glutaredoxin, an enzymatic protein, is an important component of cell viability and function. It catalyzes reactions involved in DNA synthesis and innate immunity [1,4]. Glutaredoxin is also essential in antibiotic resistance in pathogenic bacterial species. Pseudomonas aeruginosa in particular is responsible for infecting the lung tissue of its human hosts, resulting in the development of pneumonia and cystic fibrosis [3]. Because glutaredoxin is pertinent in cell proliferation of eukaryotic and bacterial cells alike, medicinal fragments that take advantage of the subtle differences in protein structure of the orthologous proteins can be synthesized and enhanced to bind bacterial glutaredoxins, without inhibiting …

Biginelli Synthesis And Characterization Of Potentially Anti-Proliferative Dihydropyrimidinone Thione Analogs, Timothy K. Summers

Theses and Dissertations

No abstract provided.

Synthesis And Characterization Of Imidazolium Salt Derivatives For Anti-Tumor Activity, Ryan W. Pearce

Williams Honors College, Honors Research Projects

Several aldehydes (butanal, pentanal, hexanal, 4-hydroxybenzaldehyde) were reacted with 1,3-bis(naphthalen-2-ylmethyl)-imidazolium bromide (1) to produce novel C² substituted imidazolium salts for the potential use against non-small cell lung cancer in humans. Compounds 2-(1-hydroxypentyl)-1,3-bis(naphthalen-2-ylmethyl)-imidazolium bromide (3) and 2-(1-hydroxyhexyl)-1,3-bis(naphthalen-2-ylmethyl)-imidazolium bromide (5) were successfully synthesized with structures supported by NMR and mass spectrometry. Characterization by ¹H NMR showed evidence of 1 in both compounds. The tumor cell growth inhibition of 3 against non-small cell lung cancer lines NCI-A549, NCI-H460, HCC827, and NCI-H1975 was tested and found to be comparable to cisplatin as measured by MTT assay. …

Polymer Interactions With Nucleic Acids Under Various Physiological Conditions, Matthew S. Obrzut

Williams Honors College, Honors Research Projects

The goal of this project is to improve our understanding of nucleic acid interactions with cationic polymers with the theory that the polymers could protect the nucleic acids from degradation caused by biological enzymes. We seek to understand what the limitations of the cationic polymers are which, in this case, is mainly polymer-DNA compatibility. This experiment utilized peptide-dextran hybrid polymers with differing functionalizations to condense anionic nucleic acids into nanometer-sized polyplexes. Techniques of dynamic light scattering and zeta-potential were utilized to determine the particle sizes and surface charges of polyplexes.

In this experiment, dextran with a molecular weight of 20 …