Chemicals and Drugs Commons^™

Comparison Of Drug Delivery With Autoinjector Versus Manual Prefilled Syringe And Between Three Different Autoinjector Devices Administered In Pig Thigh, Robert Hill, John Wilmot, Beth Belluscio, Kevin Cleary, David Lindisch, Robin Tucker, Emmanuel Wilson, Rajesh Shukla

Radiology Faculty Publications

Parenteral routes of drug administration are often selected to optimize actual dose of drug delivered, assure high bioavailability, bypass first-pass metabolism or harsh gastrointestinal environments, as well as maximize the speed of onset. Intramuscular (IM) delivery can be preferred to intravenous delivery when initiating intravenous access is difficult or impossible. Drugs can be injected intramuscularly using a syringe or an automated delivery device (autoinjector). Investigation into the IM delivery dynamics of these methods may guide further improvements in the performance of injection technologies. Two porcine model studies were conducted to compare differences in dispersion of injectate volume for different methods …

Investigation Of Tattoo Pigments By Raman Spectroscopy, Betsy Jean Yakes, Tara Jade Michael, Marianita Perez-Gonzalez, Bhakti Petigara Harp

United States Food and Drug Administration: Publications

As a result of the increase in the practice of tattooing, the US Food and Drug Administration has identified a need for improved analytical methods to detect the pigments and potential impurities in the inks. Raman spectroscopy allows for nondestructive identification of compounds and is commonly used in art, archaeology, and forensics; however, the technique has only limitedly been applied to the identification of tattoo pigments. In this study, approximately 30 inorganic, organometallic, and organic pigmentswere evaluated with Raman spectroscopy by using 532, 633, and 780-nmlasers. Individual optimization of the instrumental parameters was performed for each pigment in order to …

Bacterial Endotoxin Detection In Hyaluronic Acid-Based Medical Devices, Larissa F. Baeva, Srilekha Sarkar Das, Victoria M. Hitchins

United States Food and Drug Administration: Publications

A simple and rapid method has been developed for testing bacterial endotoxin in hyaluronic acid (HA)-based medical devices. High-molecular-weight HA (HMW HA) in solution or HA-based medical devices was digested by the enzyme hyaluronidase to reduce solution viscosity by truncating the long chains of HA and to test for bacterial endotoxin. The bacterial endotoxin level was detected and measured by kinetic chromogenic Limulus Amebocyte Lysate (LAL) assay. The method was applied to two different ophthalmic viscosurgical devices (OVDs) and one dermal filler, and may easily be adapted to use with up to 3% HA solutions and other HA-based medical devices.

Privacy And Accountability In Black-Box Medicine, Roger Allan Ford, W. Nicholson Price Ii

Law Faculty Scholarship

Black-box medicine—the use of big data and sophisticated machine learning techniques for health-care applications—could be the future of personalized medicine. Black-box medicine promises to make it easier to diagnose rare diseases and conditions, identify the most promising treatments, and allocate scarce resources among different patients. But to succeed, it must overcome two separate, but related, problems: patient privacy and algorithmic accountability. Privacy is a problem because researchers need access to huge amounts of patient health information to generate useful medical predictions. And accountability is a problem because black-box algorithms must be verified by outsiders to ensure they are accurate and …

Endothelial Progenitor Cells And Neural Progenitor Cells Synergistically Protect Cerebral Endothelial Cells From Hypoxia/Reoxygenation-Induced Injury Via Activating The Pi3k/Akt Pathway, Jinju Wang, Yusen Chen, Yi Yang, Xiang Xiao, Shuzhen Chen, Cheng Zhang, Bradley S. Jacobs, Bin Zhao, Ji C. Bihl, Yanfang Chen

Pharmacology and Toxicology Faculty Publications

Background

Protection of cerebral endothelial cells (ECs) from hypoxia/reoxygenation (H/R)-induced injury is an important strategy for treating ischemic stroke. In this study, we investigated whether co-culture with endothelial progenitor cells (EPCs) and neural progenitor cells (NPCs) synergistically protects cerebral ECs against H/R injury and the underlying mechanism.

Results

EPCs and NPCs were respectively generated from inducible pluripotent stem cells. Human brain ECs were used to produce an in vitro H/R-injury model. Data showed: 1) Co-culture with EPCs and NPCs synergistically inhibited H/R-induced reactive oxygen species (ROS) over-production, apoptosis, and improved the angiogenic and barrier functions (tube formation and permeability) in …

Analyses Of Endothelial Cells And Endothelial Progenitor Cells Released Microvesicles By Using Microbead And Q-Dot Based Nanoparticle Tracking Analysis, Jinju Wang, Yun Zhong, Xiaotang Ma, Xiang Xiao, Chuanfang Cheng, Yusen Chen, Ifeanyi Iwuchukwu, Kenneth J. Gaines, Bin Zhao, Shiming Liu, Jeffrey B. Travers, Ji C. Bihl, Yanfang Chen

Pharmacology and Toxicology Faculty Publications

Accurate analysis of specific microvesicles (MVs) from biofluids is critical and challenging. Here we described novel methods to purify and detect MVs shed from endothelial cells (ECs) and endothelial progenitor cells (EPCs) by combining microbeads with fluorescence quantum dots (Q-dots) coupled nanoparticle tracking analysis (NTA). In the in vitroscreening systems, we demonstrated that 1) anti-CD105 (EC marker) and anti-CD34 (EPC marker) conjugated-microbeads had the highest sensitivity and specificity for isolating respective MVs, which were confirmed with negative controls, CD41 and CD235a; 2) anti-CD144 (EC marker) and anti-KDR (EPC marker) conjugated-Q-dots exhibited the best sensitivity and specificity for their respective …

Ascorbic Acid For The Treatment Of Rasburicase Induced Methemoglobinemia In The Setting Of Acute Renal Failure, David J. Reeves, Lindsay Saum, Ruemu Birhiray

Scholarship and Professional Work – COPHS

Purpose A case of apparent rasburicase-induced methemoglobinemia and acute kidney injury treated with i.v. ascorbic acid because of suspected glucose-6-phosphate dehydrogenase (G6PD) deficiency is reported.

Summary A 46-year-old African-American man with a recent diagnosis of multiple myeloma and renal insufficiency was admitted to the hospital with a cough, hemoptysis, and fatigue. His medical history included hypertrophic cardiomyopathy, ventricular tachycardia, attention deficit/hyperactivity disorder, and pleural effusion. No treatments for multiple myeloma were started before hospital admission. Levofloxacin 750 mg orally daily for possible pneumonia, lenalidomide 10 mg orally daily, and dexamethasone 20 mg orally weekly were administered. Plasmapheresis was also initiated. …

Endocidal Regulation Of Secondary Metabolites In The Producing Organisms, Shiyou Li, Ping Wang, Wei Yuan, Zushang Su, Steven H. Bullard

Faculty Publications

Secondary metabolites are defined as organic compounds that are not directly involved in the normal growth, development, and reproduction of an organism. They are widely believed to be responsible for interactions between the producing organism and its environment, with the producer avoiding their toxicities. In our experiments, however, none of the randomly selected 44 species representing different groups of plants and insects can avoid autotoxicity by its endogenous metabolites once made available. We coined the term endocides (endogenous biocides) to describe such metabolites that can poison or inhibit the parent via induced biosynthesis or external applications. Dosage-dependent endocides can selectively …

Effect Of The Il-1 Receptor Antagonist Kineret® On Disease Phenotype In Mdx Mice., Margaret E. Benny Klimek, Arpana Sali, Sree Rayavarapu, Jack Van Der Meulen, Kanneboyina Nagaraju

Genomics and Precision Medicine Faculty Publications

Duchenne muscular dystrophy (DMD) is an X-linked muscle disease caused by mutations in the dystrophin gene. The pathology of DMD manifests in patients with progressive muscle weakness, loss of ambulation and ultimately death. One of the characteristics of DMD is muscle inflammation, and dystrophin-deficient skeletal muscles produce higher levels of the pro-inflammatory cytokine interleukin 1β (IL-1β) in response to toll like receptor (TLR) stimulation compared to controls; therefore, blocking the IL-1β pathway could improve the disease phenotype in mdx mice, a mouse model of DMD. Kineret® or IL-1Ra is a recombinant IL-1 receptor antagonist approved by the FDA for treating …

Biosimilars: Potential Implications For Clinicians, Misty G. Eleryan, Sophia Akhiyat, Monica Rengifo-Pardo, Alison Ehrlich

Dermatology Faculty Publications

With the expiration of patent protection for several biologics looming, the production of highly similar therapeutic agents has begun to emerge on the pharmaceutical market. These alternative drugs are referred to as biosimilars. Many anticipate that the introduction of these agents will result in a reduction in health care costs, which may create a more affordable biopharmaceutical market and also improve patient access. In contrast to generics, which are exact copies of their original products, biosimilars are not identical to their reference products. Due to concern about the safety and efficacy of biosimilars, separate regulatory approval pathways have been developed …

Micrornas Are Involved In The Development Of Morphine-Induced Analgesic Tolerance And Regulate Functionally Relevant Changes In Serpini1., Jenica D. Tapocik, Kristin Ceniccola, Cheryl L. Mayo, Melanie L. Schwandt, Matthew Solomon, Bi-Dar Wang, Truong V. Luu, Jacqueline Olender, Thomas Harrigan, Thomas M. Maynard, Greg I. Elmer, Norman H. Lee

Pharmacology and Physiology Faculty Publications

Long-term opioid treatment results in reduced therapeutic efficacy and in turn leads to an increase in the dose required to produce equivalent pain relief and alleviate break-through or insurmountable pain. Altered gene expression is a likely means for inducing long-term neuroadaptations responsible for tolerance. Studies conducted by our laboratory (Tapocik et al., 2009) revealed a network of gene expression changes occurring in canonical pathways involved in neuroplasticity, and uncovered miRNA processing as a potential mechanism. In particular, the mRNA coding the protein responsible for processing miRNAs, Dicer1, was positively correlated with the development of analgesic tolerance. The …

Can A Metallated Cyclen Species Be Used To Prepare New Odorants?, Jalynn Taylor-Farmer

UROP Posters

Scientists in the fragrance industry are constantly searching for new odors to create as well as new, more efficient processes to create them. Scientists mainly look for new ways to synthesize fragrances that will reduce the impact on the environment, produce them at lower costs, produce higher yields, and sometimes to produce a more potent odor [4]. In this research, we investigated the use of metallic macrocycles and/or metal-dioxygen chemistry to prepare new fragrances.

Cyclen (1,4,7,10-tetraazacyclododecane) has significant uses in many pharmaceutical and medicinal research developments such as advances in targeted cancer and Alzheimer’s agents. Macrocyclic amines like cyclen are …

Uvb Generates Microvesicle Particles Via Platelet-Activating Factor-Receptor Signaling: A Novel Pathway By Which A Skin-Specific Stimulus Exerts Systemic Effects, Jeffrey B. Travers, Christine M. Rapp, Katherine E. Fahy, Christina E. Borchers, Richard Simman, Langni Liu, Yanfang Chen, Ji C. Bihl

Pharmacology and Toxicology Faculty Publications

Though Ultraviolet B radiation (290-320 nm; UVB) exerts profound systemic effects, it is absorbed only in the epidermis. One important question in photobiology is how UVB signals are emanated from the epidermis. Microvesicle particles (MVP) are small (200-1000nm diameter) membrane-bound vesicles released by numerous cell types and can be found in the circulation. MVP can contain both nuclear and cytoplasmic components and are thought to provide a mechanism by which cells transmit signals systemically. Though various stressors have been demonstrated to generate MVP, the ability of UVB to exert this effect has not been demonstrated. Previous studies from ours and …

The Novel Methods For Analysis Of Exosomes Released From Endothelial Cells And Endothelial Progenitor Cells, Jinju Wang, Runmin Guo, Yi Yang, Bradley S. Jacobs, Suhong Chen, Ifeanyi Iwuchukwu, Kenneth J. Gaines, Yanfang Chen, Richard Simman, Guiyuan Lv, Keng Wu, Ji C. Bihl

Pharmacology and Toxicology Faculty Publications

Exosomes (EXs) are cell-derived vesicles that mediate cell-cell communication and could serve as biomarkers. Here we described novel methods for purification and phenotyping of EXs released from endothelial cells (ECs) and endothelial progenitor cells (EPCs) by combining microbeads and fluorescence quantum dots (Q-dots®) techniques. EXs from the culture medium of ECs and EPCs were isolated and detected with cell-specific antibody conjugated microbeads and second antibody conjugated Q-dots by using nanoparticle tracking analysis (NTA) system. The sensitivities of the cell origin markers for ECs (CD105, CD144) and EPCs (CD34, KDR) were evaluated. The sensitivity and specificity were determined by using positive …

Development Of A Chemical Genetic Screen To Determine Synergistic Compounds With Laromustine In Treating Glioblastoma Multiforme Cultured Cells, Ryan Weeks

Honors Theses

Laromustine is a chemotherapeutic sulfonylhydrazine prodrug used in clinical trials to treat acute myeloid leukemia (AML) and glioblastoma multiforme (GBM). While treatment of AML with laromustine has more demonstrative clinical success, there are enough promising data against GBM to pursue additional pre-clinical and clinical experiments. To determine the synergistic effects caused by treating cultured GBM cells with laromustine and a library of FDA-approved compounds, a chemical genetic screen was developed. To optimize the screen, optimal cultured GBM cell seed density, growth period and maximum well capacity were determined. The treatment period for a lethal dose of laromustine in cultured GBM …

The Influence Of Safety, Efficacy, And Medical Condition Severity On Natural V. Synthetic Drug Preference, Brian P. Meier, Courtney M. Lappas

Psychology Faculty Publications

Research indicates that there is a preference for natural v. synthetic products, but the influence of this preference on drug choice in the medical domain is largely unknown. We present 5 studies in which participants were asked to consider a hypothetical situation in which they had a medical issue requiring pharmacological therapy. Participants ( N = 1223) were asked to select a natural, plant-derived, or synthetic drug. In studies 1a and 1b, approximately 79% of participants selected the natural v. synthetic drug, even though the safety and efficacy of the drugs were identical. Furthermore, participants rated the natural drug as …

Piperlongumine (Piplartine) And Analogues: Antiproliferative Microtubule-Destabilising Agents, Mary J. Meegan, Seema M. Nathwani, Brendan Twamley, Daniela M. Zisterer, Niamh O'Boyle

Articles

Piperlongumine (piplartine, 1) is a small molecule alkaloid that is receiving intense interest due to its antiproliferative and anticancer activities. We investigated the effects of 1 on tubulin and microtubules. Using both an isolated tubulin assay, and a combination of sedimentation and Western blotting, we demonstrated that 1 is a tubulin-destabilising agent. This result was confirmed by immunofluorescence and confocal microscopy, which showed that microtubules in MCF-7 breast cancer cells were depolymerised when treated with 1. We synthesised a number of analogues of 1 to explore structure-activity relationships. Compound 13 had the best cytotoxic profile of this series, …

Is The High Frequency Of Postoperative Atrial Fibrillation After Cardiac And Lung Surgeries Related To Hypomagnesemia And Releases Of Ceramides And Platelet-Activating Factor?, Burton M. Altura, Nilank C. Shah, Gatha J. Shah, Aimin Zhang, Wenyan Li, Bella T. Altura

Touro College of Osteopathic Medicine (Middletown) Publications and Research

The authors discuss the possible role of hypomagnesemia, ceramides and platelet-activating factor in the incidence of postoperative atrial fibrillation after cardiac and lung surgeries.

Medical Marijuana And Pain Management: The Physician’S Catch 22, James M. Mckivigan

College of Health & Human Services (TUN) Publications and Research

In this paper, concerns connected to the usage of marijuana in treating patients are extensively analyzed. It is revealed that physicians have been in conflict with the federal government as to whether to use cannabis for medical purposes or if they should consider prescribing other drugs. A large percentage of physicians admit that marijuana could be an effective drug in treating patients, especially those with acute pain, nausea, AIDS, muscle spasms, and cancer, among other ailments. However, patients and physicians are scared of the strict laws that criminalize the use of marijuana for medical and recreational purposes. Physicians are also …

The Effects Of Testosterone Supplementation On Cognitive Functioning In Older Men, Eka Wahjoepramono, Prita Asih, Vilia Aniwiyanti, Kevin Taddei, Satvinder Dhaliwal, Stephanie Fuller, Jonathan Foster, Malcolm Carruthers, Giuseppe Verdile, Hamid R. Sohrabi, Ralph Martins

Research outputs 2014 to 2021

Reduction in testosterone levels in men during aging is associated with cognitive decline and risk of dementia. Animal studies have shown benefits for testosterone supplementation in improving cognition and reducing Alzheimer’s disease pathology. In a randomized, placebo-controlled, crossover study of men with subjective memory complaint and low testosterone levels, we investigated whether testosterone treatment significantly improved performance on various measures of cognitive functioning. Forty-four men were administered a battery of neuropsychological tests to establish the baseline prior to being randomly divided into two groups. The first group (Group A) received 24 weeks of testosterone treatment (T treatment) followed by 4 …