Pharmacology, Toxicology and Environmental Health Commons^™

A Randomized Double Blind Placebo Controlled Trial To Assess The Safety And Efficacy Of A Patented Fenugreek (Trigonella Foenum-Graecum) Seed Extract In Type 2 Diabetics, Rajinder Singh Gupta, Amarjit Singh Grover, Pawan Kumar, Apurva Goel, Samudra P. Banik, Sanjoy Chakraborty, Mehul Rungta, Manashi Bagchi, Partha Pal, Debasis Bagchi

Publications and Research

Background: Fenugreek plant (Trigonella foenum-graecum) constitutes a traditionally acclaimed herbal remedy for many human ailments including diabetes, obesity, neurodegenerative diseases, and reproductive disorders. It is also used as an effective anti-oxidative, anti-inflammatory, antibacterial, and anti-fungal agent. The seed of the plant is especially enriched in several bioactive molecules including polyphenols, saponins, alkaloids, and flavonoids and has demonstrated potential to act as an antidiabetic phytotherapeutic. A novel patented formulation (Fenfuro^®) was developed in our laboratory from the fenugreek seeds which contained >45% furostanolic saponins (HPLC).

Objective: A placebo-controlled clinical compliance study was designed to assess …

Chemical, Microbial And Safety Profiling Of A Standardized Withania Somnifera (Ashwagandha) Extract And Withaferin A, A Potent Novel Phytotherapeutic Of The Millennium, Pawan Kumar, Samudra P. Banik, Apurva Goe, Sanjoy Chakraborty, Manashi Bagchi, Debasis Bagchi

Publications and Research

Background:Withania somnifera (L.) Dunal, popularly known as Ashwagandha, is an ethnomedicinal plant with multiple pharmacotherapeutic applications. The diverse medicinal properties of the plant are largely due to the presence of withanolides, a group of C28 ergostane based steroidal lactones, with several sites of unsaturation and oxygenation. Withaferin A, a major with anolide present in Ashwagandha plant accounts for its emerging new roles to treat cancer, arthritis, inflammatory responses, immunomodulatory properties, and neuronal disorders. The root and leaf extracts are specifically important constituent materials for the development of phytotherapeutics, mostly intended for oral consumption. Several studies have been carried out …

Effectiveness And Safety Of Direct Oral Anticoagulants Among Patients With Non-Valvular Atrial Fibrillation And Multimorbidity, Amol Dhamane, Mauricio Ferri, Allison V. Keshishian, Cristina Russ, Nipun Atreja, Cynthia Gutierrez, Birol Emir, Huseyin Yuce, Manuela Di Fusco

Publications and Research

Introduction

In the USA, there is a steady rise of atrial fibrillation due to the aging population with increased morbidity. This study evaluated the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) among elderly patients with non-valvular atrial fibrillation (NVAF) and multimorbidity prescribed direct oral anticoagulants (DOACs).

Methods

Using the CMS Medicare database, a retrospective observational study of adult patients with NVAF and multimorbidity who initiated apixaban, dabigatran, or rivaroxaban from January 1, 2012 to December 31, 2017 was conducted. High multimorbidity was classified as having ≥ 6 comorbidities. Cox proportional hazard models were used to evaluate the hazard …

How Will Climate Change Affect The Future, Ashanti K. Belone, Farrukh Zia

Publications and Research

Climate Change has played a massive role in the habitat of us earth dwellers and the animals that co-exists with us. I believe that essentially climate change plays a massive role because this can dictate whether or not the earth is habitable and if a need for evacuation is necessary. Many might believe that climate change only refers to the rising temperature but that’s just the icing on the cake. Earth is a system that is very much connected, this means that changes in one area will set off a chain reaction allowing these changes to happen in many other …

Results Of A Phase 1, Randomized, Placebocontrolled First-In-Human Trial Of Griffithsin Formulated In A Carrageenan Vaginal Gel, Natalia Teleshova, Maria J. Keller, José A. Fernández Romero, Barbara A. Friedland, George W. Creasy, Marlena G. Plagianos, Laurie Ray, Patrick Barnable, Larisa Kizima, Aixa Rodriguez, Nadjet Cornejal, Claudia Melo, Gearoff Cruz Rodriguez, Sampurna Mukhopadhyay, Giulia Calenda, Shweta U. Sinkar, Thierry Bonnaire, Asa Wesenberg, Shimin Zhang, Kyle Kleinbeck, Kenneth Palmer, Mohcine Alami, Barry R. O'Keefe, Patrick Gillevet, Hong Hur, Yupu Liang, Gabriela Santone, Raina N. Fichorova, Tamara Kalir, Thomas M. Zydowsky

Publications and Research

HIV pre-exposure prophylaxis (PrEP) is dominated by clinical therapeutic antiretroviral (ARV) drugs. Griffithsin (GRFT) is a non-ARV lectin with potent anti-HIV activity. GRFT’s preclinical safety, lack of systemic absorption after vaginal administration in animal studies, and lack of cross-resistance with existing ARV drugs prompted its development for topical HIV PrEP. We investigated safety, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of PC-6500 (0.1% GRFT in a carrageenan (CG) gel) in healthy women after vaginal administration. This randomized, placebo-controlled, parallel group, double-blind first-in-human phase 1 study enrolled healthy, HIV-negative, non-pregnant women aged 24–45 years. In the open label period, all participants (n …

Chemical Exposure From Manufactured Gas Plants: Public Health Risks?, Aneeza Hussain

Publications and Research

This project aims at identifying the chemicals and their risk factors to public health, which were found underneath Public Place, a brownfield next to the Gowanus Canal. The site is heavily contaminated with coal tar — a toxic chemical by-product of gas manufacturing, which happened at the site for 100 years until the gas plant closed down in the 1960s and the land was seized by the city. Recently, the city has planned to develop Public Place into “Gowanus Green” and which will be comprised of a school and low-income housing units on this site. The aim of this research …

Understanding Of Aerosol Transmission Of Covid 19 In Indoor Environments, Adama Barro, Cathal O'Toole, Jacob S. Lopez, Matthew Quinones, Sherene Moore

Publications and Research

Our reason for discussing severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) or 2019 novel corona virus (Covid-19), is to understand its aerosol transmission characteristics in indoor spaces and to mitigate further spread of this disease by designing a new HVAC system. The problem that we are tackling is the spread of covid-19 droplets through aerosol transmission by looking at potential engineering solutions to the existing HVAC systems. The purpose is to eradicate the spread of the COVID-19 by testing indoor spaces in an effort to understand the effectiveness of ventilation controls. We believe that scientists and engineers have not …

Pyronaridine Exerts Potent Cytotoxicity On Human Breast And Hematological Cancer Cells Through Induction Of Apoptosis, Paulina J. Villanueva, Alberto Martinez, Sarah T. Baca, Rebecca E. Dejesus, Manuel Larragoity, Lisett Contreras, Denisse A. Gutierrez, Armando Varela-Ramirez, Renato J. Aguilera

Publications and Research

The potent antimalarial drug pyronaridine (PND) was tested for its potential as an anticancer drug. After exposing cancerous (17) and non-cancerous (2) cells to PND for 72 hr, PND was found to exhibit consistent and potent cytotoxic activity at low micromolar (μM) concentrations that ranged from 1.6 μM to 9.4 μM. Moreover, PND exerted a significant selective cytotoxicity index (SCI) on five out of seven breast cancer cell lines tested, with favorable values of 2.5 to 4.4, as compared with the non-cancerous breast MCF-10A cell line. By using the same comparison, PND exhibited a significant SCI on three out of …

Postmortem Toxicology Of New Synthetic Opiods, Marta Concheiro, Rachel Chesser, Justine Pardi, Gail Cooper

Publications and Research

One hundred fifteen Americans die every day from opioid overdose. These overdose fatalities have been augmented by the increased availability of potent synthetic opioids, such as fentanyl and its derivatives. The death rate of synthetic opioids, other than methadone, increased by 72.2% from 2014 to 2015, and doubled from 2015 to 2016, situating the USA in the midst of an opioid overdose epidemic. The analytical identification of these opioids in postmortem samples and the correct toxicological data interpretation is critical to identify and implement preventive strategies. This article reviews the current knowledge of postmortem toxicology of synthetic opioids and the …

An Interview With Cesare Montecucco, Mandë Holford, Andreas Rummel

Publications and Research

Cesare Montecucco is a member of the board of various leading scientific journals. His research focus is on the regeneration of the peripheral nervous system and on the mechanisms of action of toxins and related diseases, including tetanus, botulism, anthrax and Helicobacter pylori-associated diseases. In this interview, we talked to Cesare Montecucco about his career, learning and culture.

Regulation Of Radioactive Fracking Waste, Elizabeth Ann Glass Geltman, Nichole Leclair

Publications and Research

Natural gas extracted form shale reached record production totals in 2015 in the United States and the US Energy Information Administration (EIA) forecasts natural gas production will continue to increase. Wastes from shale gas extraction can contain the radioactive isotopes radium-226 (Ra-226) and radium-228 (Ra-228), which decay further into radon (Rn). Exposure to radon, a form of naturally occurring radioactive materials (NORM), is the leading cause of lung cancer in the United States, after smoking. This article explores how states handle the disposal of technologically enhanced naturally occurring radioactive materials (TENORM) and/or NORM waste from oil and gas operations to …

In Anthropocene Air: Deleuze's Encounter With Shakespeare, Steven Swarbrick

Publications and Research

No abstract provided.

In Silico Study Of Newly Synthesized Opioid Analgesics Bound To Three Opioid Receptors, Abdullah Allaoa, Mai Zahran

Publications and Research

Opioids are the most widely used drugs for the treatment of moderate to severe, chronic pain. They achieve antinociception by activation of mu (MOR-1), kappa (KOR-1), and delta (DOR-1) opioid receptors. Natural products found in kratom plant, Mitragyna speciosa, represent diverse chemical groups with opioid activity, providing opportunities to better understand opioid pharmacology. Pharmacology studies show that Mitragynine pseudoindoxyl is a mu agonist/delta antagonist opioid with a signaling bias for G-protein-mediated signaling pathways in vitro and which produced potent antinociception in vivo. Respiratory depression assays along with other behavioral testing also showed that some of the major problems …

Stability Of Synthetic Cathinones In Oral Fluid Samples, Briana Miller, Jiyoung Kim, Marta Concheiro

Publications and Research

Synthetic cathinones are new stimulant drugs derived from cathinone that have been sold as “legal highs” worldwide. These compounds can elicit powerful effects such as delusions, hallucinations as well as other potentially dangerous behavior. New analogs with varying effects and potencies are constantly introduced in the market to evade legislation, and they are not detected by routine screening and confirmation methods. Oral fluid is an alternative matrix of increasing interest in forensic toxicology. Its collection is non-invasive and easily supervised, and positive drug findings typically reflect recent drug exposure. The focus of this research was to develop a method for …

Ck2—An Emerging Target For Neurological And Psychiatric Disorders, Julia Castello, Andre Ragnauth, Eitan Friedman, Heike Rebholz

Publications and Research

Protein kinase CK2 has received a surge of attention in recent years due to the evidence of its overexpression in a variety of solid tumors and multiple myelomas as well as its participation in cell survival pathways. CK2 is also upregulated in the most prevalent and aggressive cancer of brain tissue, glioblastoma multiforme, and in preclinical models, pharmacological inhibition of the kinase has proven successful in reducing tumor size and animal mortality. CK2 is highly expressed in the mammalian brain and has many bona fide substrates that are crucial in neuronal or glial homeostasis and signaling processes across synapses. Full …

Bioanalysis For Cocaine, Opiates, Methadone And Amphetamines Exposure Detection During Pregnancy, Marta Concheiro, Elena Lendoiro, Ana De Castro, Eva Gonzalez-Colmenero, Ana Concheiro-Guisan, Patricia Penas-Silva, Manuel Macias-Cortina, Angelines Cruz-Landeira, Manuel Lopez-Rivadulla

Publications and Research

Drug exposure during pregnancy constitutes a major legal issue and public health concern. Drug and metabolite determination in biological matrices from mother and newborn is an objective indication of prenatal drug exposure. However, limited data are available regarding the interpretation of these analytical results in terms of window of detection and degree of exposure. We collected paired maternal hair, meconium, placenta and umbilical cord from 727 mother-newborn dyads. We analyzed these specimens by liquid chromatography tandem mass spectrometry for the determination of cocaine, opioids, methadone and amphetamines, and compared the analytical results from the four different matrices. The cases were …

Airborne Infectious Agents And Other Pollutants In Automobiles For Domestic Use: Potential Health Impacts And Approaches To Risk Mitigation, Syed A. Sattar, Kathryn E. Wright, Bahram Zargar, Joseph R. Rubino, M. Khalid Ijaz

Publications and Research

Theworld total of passenger cars is expected to go fromthe current one billion to >2.5 billion by 2050. Cars for domestic use account for ∼74% of the world’s yearly production ofmotorized vehicles. In North America, ∼80% of the commuters use their own car with another 5.6% travelling as passengers.With the current life-expectancy of 78.6 years, the average North American spends 4.3 years driving a car! This equates to driving 101 minutes/day with a lifetime driving distance of nearly 1.3 million km inside the confined and often shared space of the car with exposure to a mix of potentially harmful pathogens, …

Inquiry Into The Implementation Of Bush’S Executive Order 13211 And The Impact On Environmental And Public Health Regulation, Elizabeth Ann Glass Geltman, Gunwant Gill, Miriam Jovanovic

Publications and Research

Executive Order 13211, promulgated in 2001, requires the federal government to consider the impact of federal action on energy independence as part of the George W. Bush’s National Energy Policy. This law review examines whether EO 13211 was used to curtail environmental protection and natural resource conservation. The article begins with a review of the procedure required of federal agencies under EO 13211 and its associated documents. The paper then examines case law and published federal rulemaking proceedings and examines how federal agencies apply tests to evaluate the potential energy effect. The study concludes that EO 13211 strikes a reasonable …

Beyond Baby Steps An Empirical Study Of The Impact Of Environmental Justice Executive Order 12898, Elizabeth Ann Glass Geltman, Gunwant Gill, Miriam Jovanovic

Publications and Research

This study evaluated the impact of Executive Order (EO) 12898 to advance environmental justice. We conducted a review evaluating the frequency and effective use of EO 12898 since execution with particular focus following President Obama’s Plan EJ 2014. We found that both EO 12898 and Plan EJ 2104 had little, if any, impact on federal regulatory decision making. To the extent federal agencies discussed EO 12898, most did so in boilerplate rhetoric that satisfied compliance but was devoid of detailed thought or analysis. In the 21st year, with the exception of the Environmental Protection Agency, very little federal regulatory activity …

Drilling For Common Ground: How Public Opinion Tracks Experts In The Debate Over Federal Regulation Of Shale Oil & Gas Extraction, Elizabeth Ann Glass Geltman

Publications and Research

Public interest in environmental and health impacts from shale oil and gas extraction (what the public calls “fracking”) is growing. Industry claims the public outcry against the new technology is not grounded in science. In February 2013, Resources for the Future (“RFF”) published a list of high priority “risk pathways” that experts from NGOs, academia, government, and industry all agreed were real concerns about fracking. This article used the risk matrix to evaluate whether public comments in dockets of federal agencies that proposed regulation concerning hydraulic fracturing tracked expert concern. The article found that the public tracked many of the …

Impact Of Executive Order 13211 On Environmental Regulation: An Empirical Study, Elizabeth Ann Glass Geltman

Publications and Research

A great deal has been written about the Energy Policy Act of 2005 exempting oil and gas operations using hydraulic fracturing from the purview of certain federal environmental laws. Far less attention has been paid to George W. Bush’s Executive Order 13211 (EO 13211), entitled “Actions Concerning Regulations that Significantly Affect Energy Supply, Distribution or Use.” The executive order requires federal agencies to evaluate the impact of federal regulations on “supply, distribution and use of energy.” This study examined the impact of EO 13211 on United States environmental and conservation regulations proposed and promulgated by federal agencies. The study found …

Nitric Oxide-Releasing Aspirin Suppresses Nf-Κb Signaling In Estrogen Receptor Negative Breast Cancer Cells In Vitro And In Vivo, Niharika Nath, Mitali Chattopadhyay, Deborah B. Rodes, Anna Nazarenko, Ravinder Kodela, Khosrow Kashfi

Publications and Research

Estrogen receptor negative (ER(−)) breast cancer is aggressive, responds poorly to current treatments and has a poor prognosis. The NF-κB signaling pathway is implicated in ER(−) tumorigenesis. Aspirin (ASA) is chemopreventive against ER(+) but not for ER(−) breast cancers. Nitric oxide-releasing aspirin (NO-ASA) is a safer ASA where ASA is linked to an NO-releasing moiety through a spacer. In vitro, we investigated anti-proliferation effects of NO-ASA (para- and meta-isomers) against ER(−) breast cancer cells MDA-MB-231 and SK-BR-23, effects on NF-κB signaling, and reactive oxygen species by standard techniques. In vivo, effects of NO-ASA were evaluated in a mouse xenograft model …

Acid-Base Properties Of The Adsorption Of Synthetic Dyes From Solutions, Rada-Mayya Kostadinova, Gabriela Sikorska, Michelle Naidoo, Abel E. Navarro

Publications and Research

The presence of synthetic dyes is often underestimated in environmental protection. However, it has been demonstrated the impact of colored compounds in ecology and human health. Green tea (GT) and peppermint (PM) tea bag wastes were used as potential adsorbents of dyes from aqueous solutions to evaluate the effect of pH on the adsorption. Basic yellow 57, basic blue 99 and crystal violet were chosen as model dyes due to their widespread use in the industry. Dye solutions at different pH values were placed in contact with the adsorbents in batch experiments at room temperature. Results indicate that crystal violet …

Laboratory Evaluation Of A Prospective Remediation Method For Pcb-Contaminated Paint, Erin K H Saitta, Michael J. Gittings, Christian Clausen, Jacqueline Quinn, Cherie L. Yestrebsky

Publications and Research

Background: Paint laden with polychlorinated biphenyls (PCBs) often acts as a point source for environmental contamination. It is advantageous to address contaminated paint before the PCBs transport to surrounding media; however, current disposal methods of painted material introduce a variety of complications. Previous work demonstrates that PCBs can be broken down at ambient temperatures and pressures through a degradation process involving magnesium metal and acidified ethanol. This report is an extension of that work by describing the development of a delivery system for said reaction in preparation for a field test. Two treatment options including the Activated Metal Treatment System …

Theodorakis Studies Effects Of Toxic Chemicals, Aldemaro Romero Jr.

Publications and Research

No abstract provided.

When Substance Abuse And Mental Illness Combine, Aldemaro Romero Jr.

Publications and Research

No abstract provided.

Weaponizing Tear Gas: Bahrain’S Unprecedented Use Of Toxic Chemical Agents Against Civilians., Richard Sollom, Holly G. Atkinson

Publications and Research

The Bahraini government’s response to the early 2011 pro-democracy protests was brutal, systematic, and violent. In addition to birdshot and rubber bullets, government law enforcement attacked unarmed protestors with toxic chemical agents including tear gas. The government’s crackdown on the medical profession was especially harmful, as security forces arrested and detained doctors, raided health facilities, and obstructed patients from receiving necessary care. This report’s findings are based on field research that the authors conducted in Bahrain (April 2012) to investigate excessive use of force by law enforcement officials since June 2011—the end of Bahrain’s state of emergency. The medico-legal team …

Antidepressant Stimulation Of Cdp-Diacylglycerol Synthesis Does Not Require Monoamine Reuptake Inhibition, Ashiwel S. Undieh, Marwa A. Aboukhatwa

Publications and Research

Background: Recent studies demonstrate that diverse antidepressant agents increase the cellular production of the nucleolipid CDP-diacylglycerol and its synthetic derivative, phosphatidylinositol, in depression-relevant brain regions. Pharmacological blockade of downstream phosphatidylinositide signaling disrupted the behavioral antidepressant effects in rats. However, the nucleolipid responses were resistant to inhibition by serotonin receptor antagonists, even though antidepressant-facilitated inositol phosphate accumulation was blocked. Could the neurochemical effects be additional to the known effects of the drugs on monoamine transmitter transporters? To examine this question, we tested selected agents in serotonin-depleted brain tissues, in PC12 cells devoid of serotonin transporters, and on the enzymatic activity of …

Maternal Cocaine Administration In Mice Alters Dna Methylation And Gene Expression In Hippocampal Neurons Of Neonatal And Prepubertal Offspring, Svetlana I. Novikova, Fang He, Jie Bai, Nicholas J. Cutrufello, Michael S. Lidow, Ashiwel S. Undieh

Publications and Research

Previous studies documented significant behavioral changes in the offspring of cocaine-exposed mothers. We now explore the hypothesis that maternal cocaine exposure could alter the fetal epigenetic machinery sufficiently to cause lasting neurochemical and functional changes in the offspring. Pregnant CD1 mice were administered either saline or 20 mg/kg cocaine twice daily on gestational days 8–19. Male pups from each of ten litters of the cocaine and control groups were analyzed at 3 (P3) or 30 (P30) days postnatum. Global DNA methylation, methylated DNA immunoprecipitation followed by CGI2 microarray profiling and bisulfite sequencing, as well as quantitative real-time RT-PCR gene expression …

Discovery Shook Medical, Pharmaceutical Industries, Aldemaro Romero Jr., David Gilmore

Publications and Research

No abstract provided.