Chemicals and Drugs Commons^™

Piwi Is Required To Limit Exhaustion Of Aging Somatic Stem Cells, Pedro Sousa-Victor, Arshad Ayyaz, Rippei Hayashi, Yanyan Qi, David T. Madden, Victoria V. Lunyak, Heinrich Jasper

Faculty Publications & Research of the TUC College of Pharmacy

Please see the graphical abstract in the supplemental files.

Steroid Hormone Receptors As Prognostic Markers In Breast Cancer, Maggie C. Louie, Mary B. Sevigny

Faculty Publications & Research of the TUC College of Pharmacy

Despite the existence of many promising anti-cancer therapies, not all breast cancers are equally treatable, due partly to the fact that focus has been primarily on a few select breast cancer biomarkers- notably ERα, PR and HER2. In cases like triple negative breast cancer (ERα-, PR-, and HER2-), there is a complete lack of available biomarkers for prognosis and therapeutic purposes. The goal of this review is to determine if other steroid receptors, like ERβ and AR, could play a prognostic and/or therapeutic role. Data from various in vitro, in vivo, and clinical breast cancer studies were examined …

Mucosal Fluid Glycoprotein Dmbt1 Suppresses Twitching Motility And Virulence Of The Opportunistic Pathogen Pseudomonas Aeruginosa, Jianfang Li, Matteo E. O. Metruccio, David J. Evans, Suzanne M. J. Fleiszig

Faculty Publications & Research of the TUC College of Pharmacy

It is generally thought that mucosal fluids protect underlying epithelial surfaces against opportunistic infection via their antimicrobial activity. However, our published data show that human tear fluid can protect against the major opportunistic pathogen Pseudomonas aeruginosa independently of bacteriostatic activity. Here, we explored the mechanisms for tear protection, focusing on impacts of tear fluid on bacterial virulence factor expression. Results showed that tear fluid suppressed twitching motility, a type of surface-associated movement conferred by pili. Previously, we showed that twitching is critical for P. aeruginosa traversal of corneal epithelia, exit from epithelial cells after internalization, and corneal virulence. Inhibition …

Similar Adverse Events From Two Disparate Agents Implicate Lipid Inflammatory Mediators For A Role In Anxiety States, Gordon Mccarter, Lauren B. Blanchard

Faculty Publications & Research of the TUC College of Pharmacy

We recently reported a case in which a 54-year-old male experienced maintenance insomnia, generalized anxiety and panic symptoms associated with consumption of a fish oil supplement enriched in eicosapentaenoic acid (EPA). We report here that the same patient has experienced identical but more severe symptoms in response to the use of the leukotriene receptor antagonist montelukast, in accordance with other cases reported to the Food and Drug Administration. Since omega-3 fatty acids like EPA are precursors for the biosynthesis of eicosanoids including leukotrienes, a common factor to these psychiatric adverse events may be perturbations in this highly complex system of …

221 Newborn-Screened Neonates With Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency: Findings From The Inborn Errors Of Metabolism Collaborative, K Bentler, S Zhai, S Elsbecker, G Arnold, B Burton, J Vockley, C Cameron, S Hiner, M Edick, S Berry, J Thomas, M Dodge, R Singh, S Lakshman, David Kronn, Inborn Errors Of Metabolism Collaborative

NYMC Faculty Publications

Introduction: There is limited understanding of relationships between genotype, phenotype and other conditions contributing to health in neonates with medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD) identified through newborn screening. Methods: Retrospective analysis of comprehensive data from a cohort of 221 newborn-screened subjects identified as affected with MCADD in the Inborn Errors of Metabolism-Information System (IBEM-IS), a long term follow-up database of the Inborn Errors of Metabolism Collaborative, was performed. Results: The average age at notification of first newborn screen results to primary care or metabolic providers was 7.45 days. The average octanoylcamitine (C8) value on first newborn screen was 11.2 …

Sweetening Of Glutamine Metabolism In Cancer Cells By Rho Gtpases Through Convergence Of Multiple Oncogenic Signaling Pathways, Thambi Dorai, John T. Pinto, Arthur J. L. Cooper

NYMC Faculty Publications

Comment on: Lukey MJ, Greene KS, Erickson JW, et al. The oncogenic transcription factor c-Jun regulates glutaminase expression and sensitizes cells to glutaminase-targeted therapy. Nat Commun 2016;7:11321.

Antimicrobials: A Global Alliance For Optimizing Their Rational Use In Intra-Abdominal Infections (Agora), M Sartelli, D Weber, E Ruppe, M Bassetti, B Wright, L Ansaloni, F Catena, F Coccolini, Rifat Latifi, T Zakrison, A Corcione, R Melotti, C Viscoli, P Viale

NYMC Faculty Publications

Intra-abdominal infections (IAI) are an important cause of morbidity and are frequently associated with poor prognosis, particularly in high-risk patients. The cornerstones in the management of complicated IAIs are timely effective source control with appropriate antimicrobial therapy. Empiric antimicrobial therapy is important in the management of intra-abdominal infections and must be broad enough to cover all likely organisms because inappropriate initial antimicrobial therapy is associated with poor patient outcomes and the development of bacterial resistance. The overuse of antimicrobials is widely accepted as a major driver of some emerging infections (such as C. difficile), the selection of resistant pathogens in …

A Rare Case Report Of Probable Indigotindisulfonate Sodium-Induced Cardiac Arrest, Andrew P. Smith, Catherine A. Millares-Sipin, Henry Cohen, William Lois

Touro College of Pharmacy (New York) Publications and Research

Background: Indigotindisulfonate (Indigo Carmine, American Regent, Shirely, NY) is a blue dye that is commonly used for localizing ureteral orifices during surgery. In general, it is safe and biologically inactive, with the package insert citing only rare idiosyncratic reactions and mild pressor effects in some patients. We report a case of a severe life-threatening anaphylactoid reaction due to indigotindisulfonate following intravenous administration.

Case Report: We describe a case of a 42-year-old female admitted for a total abdominal hysterectomy. Upon arrival to the operating room, her heart rate (HR) was 80/min, blood pressure (BP) was 135/75 mm Hg, and …

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.

Postprandial Paraoxonase 1 Activity Following Consumption Of Recommended Amounts Of Mixed Meals In Healthy Males, Noriko Kameyama, Chizuko Maruyama, Kazuhiko Kotani, Russell Caccavello, Alejandro Gugliucci, Sadako Matsui, Taro Maruyama

Faculty Publications & Research of the TUC College of Osteopathic Medicine

Aim: Postprandial lipid level increases induce oxidative stress, which is involved in atherogenesis. The antioxidant properties of paraoxonase 1 (PON1) have attracted attention. However, changes in postprandial PON1 levels differ across prior studies, and changes in PON1 lactonase activity, potentially relevant to PON1 physiology, after the consumption of ordinary meals are unknown. Herein we evaluated postprandial serum lipid levels and PON1 changes following mixed-meal consumption of the amounts recommended for ordinary meals.
Methods: Nine healthy male volunteers consumed three different meals in a randomized cross-over design. The test meals were as follows: S, white rice; SMF, S with …

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 …

Artificial Sweeteners And Weight Gain: Fighting Or Feeding The Obesity Epidemic?, Shanna Frisch

The Science Journal of the Lander College of Arts and Sciences

Our world has developed an obsession with weight control and, as a result, has begun replacing high calorie foods with low-fat and non-caloric substitutes. Artificial sweeteners are a widely used solution to this growing problem. Though the intention when using artificial sweeteners is to lose weight, studies have shown that the opposite sometimes occurs. Researchers attempt to explain this surprising phenomenon with multiple hypotheses. Lack of appetite suppression and reward response may cause individuals to search for more food and to consume more calories. Artificial sweeteners can also have negative affects on biological mechanisms such as resting metabolic rate, as …

Effects Of Moderate Intake Of Alcohol On Coronary Heart Disease, Eli Derdik

The Science Journal of the Lander College of Arts and Sciences

The french paradox is caused by an inconsistency with scientific experimentation: The French have a very high intake of saturated fat and cholesterol, which is associated with coronary heart disease, yet they have un-commensurately low levels of deaths due to this disease. It has been proposed that alcohol, as a part of the French diet, is the factor that helps decrease the risk of heart disease in the French population by 20-30%. Research has been gathered from many medical journals to create a larger and more accurate perspective to determine if alcohol has any effect on coronary heart disease. Experiments …

Isavuconazole In The Treatment Of Invasive Aspergillosis And Mucormycosis Infections, Monica A. Donnelley, Elizabeth S. Zhu, George R. Thompson Iii

Faculty Publications & Research of the TUC College of Pharmacy

We have a limited arsenal with which to treat invasive fungal infections caused by Aspergillus and Mucorales. The morbidity and mortality for both pathogens remains high. A triazole antifungal, isavuconazole, was recently granted approval by the US Food and Drug Administration and the European Medicines Agency for the treatment of invasive aspergillosis and mucormycosis. A randomized double-blind comparison trial for the treatment of invasive aspergillosis found isavuconazole noninferior to voriconazole. A separate, open-label study evaluating the efficacy of isavuconazole in the treatment of mucormycosis found comparable response rates to amphotericin B and posaconazole treated historical controls. The prodrug isavuconazonium sulfate …

Pharmacology Of Dextromethorphan: Relevance To Dextromethorphan/Quinidine (Nuedexta®) Clinical Use, Charles P. Taylor, Stephen F. Traynelis, Joao Siffert, Laura E. Pope, Rae Reiko Matsumoto

Faculty Publications & Research of the TUC College of Pharmacy

Dextromethorphan (DM) has been used for more than 50 years as an over-the-counter antitussive. Studies have revealed a complex pharmacology of DM with mechanisms beyond blockade of N-methyl-D-aspartate (NMDA) receptors and inhibition of glutamate excitotoxicity, likely contributing to its pharmacological activity and clinical potential.

DM is rapidly metabolized to dextrorphan, which has hampered the exploration of DM therapy separate from its metabolites. Coadministration of DM with a low dose of quinidine inhibits DM metabolism, yields greater bioavailability and enables more specific testing of the therapeutic properties of DM apart from its metabolites. The development of the drug combination DM hydrobromide …

Euphoria From Drinking Alcoholic Beverages May Be Due To Reversible Constriction Of Cerebral Blood Vessels: Potential Roles Of Unrecognized Ionized Hypomagnesemia, And Release Of Ceramides And Platelet-Activating Factor, Burton M. Altura, Aimin Zhang, Nilank C. Shah, Gatha J. Shah, Asefa Gebrewold, Bella T. Altura

Touro College of Osteopathic Medicine (Middletown) Publications and Research

The authors discuss the feeling of euphoria when drinking alcohol. They summarize studies that suggest this feeling is due to blood vessel constriction, and explain why they believe that the specific mechanism that results in euphoria is the rapid, reversible release o free magnesium ions ([Mg2+]) coupled to the release of ceramides and platelet-activating factor (PAF).

Orexin Receptor Activation Generates Gamma Band Input To Cholinergic And Serotonergic Arousal System Neurons And Drives An Intrinsic Ca(2+)-Dependent Resonance In Ldt And Ppt Cholinergic Neurons, Masaru Ishibashi, Iryna Gumenchuk, Bryan Kang, Catherine Steger, Elizabeth Lynn, Nancy Molina, Leonard M. Eisenberg, Christopher S. Leonard

NYMC Faculty Publications

A hallmark of the waking state is a shift in EEG power to higher frequencies with epochs of synchronized intracortical gamma activity (30-60 Hz) - a process associated with high-level cognitive functions. The ascending arousal system, including cholinergic laterodorsal (LDT) and pedunculopontine (PPT) tegmental neurons and serotonergic dorsal raphe (DR) neurons, promotes this state. Recently, this system has been proposed as a gamma wave generator, in part, because some neurons produce high-threshold, Ca(2+)-dependent oscillations at gamma frequencies. However, it is not known whether arousal-related inputs to these neurons generate such oscillations, or whether such oscillations are ever transmitted to neuronal …

Biological Reasons For The Neurotoxic Effects Of Mdma (‘Ecstasy’) On The Developing Fetus, Leah Schneeweiss

The Science Journal of the Lander College of Arts and Sciences

MDMA (3, 4-methylenedioxymethamphetamine) is an illicit, recreational drug known by many individuals as ‘Ecstasy.’ MDMA has gained popularity over the past decade and has become a drug of choice at dance parties and clubs because of the stimulating and hallucinogenic effects that it has on the central nervous system. Scientists have determined that MDMA causes neurotoxic damage to adults by harming the serotonergic system in the adult brain. Researchers discovered that embryos exposed to MDMA while in utero also suffer neurotoxic deficits, although not due to impairments in the embryos’ serotonergic systems. These deficits arise because of the cortisol increase …

A-803467, A Tetrodotoxin-Resistant Sodium Channel Blocker, Modulates Abcg2-Mediated Mdr In Vitro And In Vivo, Nagaraju Anreddy, Atish Patel, Yun-Kai Zhang, Yi-Jun Wang, Suneet Shukla, Rishil J. Kathawala, Priyank Kumar

Touro College of Pharmacy (New York) Publications and Research

ATP-binding cassette subfamily G member 2 (ABCG2) is a member of the ABC transporter superfamily proteins, which has been implicated in the development of multidrug resistance (MDR) in cancer, apart from its physiological role to remove toxic substances out of the cells. The diverse range of substrates of ABCG2 includes many antineoplastic agents such as topotecan, doxorubicin and mitoxantrone. ABCG2 expression has been reported to be significantly increased in some solid tumors and hematologic malignancies, correlated to poor clinical outcomes. In addition, ABCG2 expression is a distinguishing feature of cancer stem cells, whereby this membrane transporter facilitates resistance to the …

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 …

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 …

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. …

Ghrelin, Timo D. Müller, Rubén Nogueiras, Mark L. Andermann, Zane B. Andrews, Stefan Anker, Jesús Argente, Allan Geliebter

Lander College of Arts and Sciences Publications and Research

Background: The gastrointestinal peptide hormone ghrelin was discovered in 1999 as the endogenous ligand of the growth hormone secretagogue receptor. Increasing evidence supports more complicated and nuanced roles for the hormone, which go beyond the regulation of systemic energy metabolism.

Scope of review: In this review, we discuss the diverse biological functions of ghrelin, the regulation of its secretion, and address questions that still remain 15 years after its discovery.

Major conclusions: In recent years, ghrelin has been found to have a plethora of central and peripheral actions in distinct areas including learning and memory, gut motility …

A Microrna-1280/Jag2 Network Comprises A Novel Biological Target In High-Risk Medulloblastoma, Fengfei Wang, Marc Remke, Tze-Chen Hsieh, Lizi Wu, Cynthia Hawkins, Joseph M. Wu, Erxi Wu

NYMC Faculty Publications

Over-expression of PDGF receptors (PDGFRs) has been previously implicated in high-risk medulloblastoma (MB) pathogenesis. However, the exact biological functions of PDGFRα and PDGFRβ signaling in MB biology remain poorly understood. Here, we report the subgroup specific expression of PDGFRα and PDGFRβ and their associated biological pathways in MB tumors. c-MYC, a downstream target of PDGFRβ but not PDGFRα, is involved in PDGFRβ signaling associated with cell proliferation, cell death, and invasion. Concurrent inhibition of PDGFRβ and c-MYC blocks MB cell proliferation and migration synergistically. Integrated analysis of miRNA and miRNA targets regulated by both PDGFRβ and c-MYC reveals that increased …

Hydroxamic Acid-Based Histone Deacetylase (Hdac) Inhibitors Can Mediate Neuroprotection Independent Of Hdac Inhibition, Sama Sleiman, Yan-Ling Zhang, Jennifer Gale, Manuela Basso, Giovanni Coppola, John T. Pinto, Rajiv Ratan

NYMC Faculty Publications

Histone deacetylase (HDAC) inhibition improves function and extends survival in rodent models of a host of neurological conditions, including stroke, and neurodegenerative diseases. Our understanding, however, of the contribution of individual HDAC isoforms to neuronal death is limited. In this study, we used selective chemical probes to assess the individual roles of the Class I HDAC isoforms in protecting Mus musculus primary cortical neurons from oxidative death. We demonstrated that the selective HDAC8 inhibitor PCI-34051 is a potent neuroprotective agent; and by taking advantage of both pharmacological and genetic tools, we established that HDAC8 is not critically involved in PCI-34051's …

Hdac8 And Stat3 Repress Bmf Gene Activity In Colon Cancer Cells, Y Kang, Hui Nian, P Rajendran, W Dashwood, John T. Pinto, E Ho, R Dashwood

NYMC Faculty Publications

Histone deacetylase (HDAC) inhibitors are undergoing clinical trials as anticancer agents, but some exhibit resistance mechanisms linked to anti-apoptotic Bcl-2 functions, such as BH3-only protein silencing. HDAC inhibitors that reactivate BH3-only family members might offer an improved therapeutic approach. We show here that a novel seleno-α-keto acid triggers global histone acetylation in human colon cancer cells and activates apoptosis in a p21-independent manner. Profiling of multiple survival factors identified a critical role for the BH3-only member Bcl-2-modifying factor (Bmf). On the corresponding BMF gene promoter, loss of HDAC8 was associated with signal transducer and activator of transcription 3 (STAT3)/specificity protein …

Protein Binding Drug-Drug Interaction Between Warfarin And Tizoxanide In Human Plasma, Eduard Mullokandov, Jennifer Ahn, Andrew Szalkiewicz, Mariana Babayeva

Touro College of Pharmacy (New York) Publications and Research

The goal of the in vitro research was to evaluate the potential for inhibition of warfarin protein binding by tizoxanide. Warfarin was of particular interest for the present investigation because it has been shown to be highly bound to plasma proteins and is a narrow therapeutic index drug. Tizoxanide is an active metabolite of an anti-infective prodrug nitazoxanide and also highly protein-bound medication. Both drugs are expected to be co-administered clinically. Protein binding of warfarin was investigated using a centrifugal ultrafiltration technique. Co-administration of tizoxanide significantly inhibited protein binding of warfarin for all concentrations tested. Tizoxanide increased free fraction (fu) …

Involvement Of Sigma-1 Receptors In The Antidepressant-Like Effects Of Dextromethorphan, Linda Nguyen, Matthew J. Robson, Jason R. Healy, Anna L. Scandinaro, Rae Reiko Matsumoto

Faculty Publications & Research of the TUC College of Pharmacy

Dextromethorphan is an antitussive with a high margin of safety that has been hypothesized to display rapid-acting antidepressant activity based on pharmacodynamic similarities to the N-methyl-D-aspartate (NMDA) receptor antagonist ketamine. In addition to binding to NMDA receptors, dextromethorphan binds to sigma-1 (s1) receptors, which are believed to be protein targets for a potential new class of antidepressant medications. The purpose of this study was to determine whether dextromethorphan elicits antidepressant-like effects and the involvement of s1 receptors in mediating its antidepressant-like actions. The antidepressant-like effects of dextromethorphan were assessed in male, Swiss Webster mice using the forced swim test. Next, …

Cardiac Troponin Assessment Following Atrial Fibrillation Ablation: Implications For Chest Pain Evaluation, Jason C. Rubenstein, Jason T. Jacobson, Jeffrey J. Goldberger, Rod Passman, Alan H. Kadish, Michael H. Kim

Office of the President Publications and Research

Background: The range of elevation of troponin I (tI) that is within expected limits from left atrial radiofrequency ablation for atrial fibrillation (AF) is not well described, though such information may be of clinical value.

Objectives: Identify the expected range of tI values post-atrial fibrillation (AF) ablation.

Methods: 31 patients undergoing AF ablation had a single tI level drawn the day following the procedure. Clinical variables were also collected, such as ablation type and radiofrequency (RF) time.

Results: Paroxysmal AF was present in 23 patients, and 8 had chronic AF. The average RF time was 2627.8 …