Pharmacology, Toxicology and Environmental Health Commons^™

Prolactin And Fmri Response To Skf38393 In The Baboon, Brad D. Miller, Lauren A. Marks, Jonathan M. Koller, Blake J. Newman, G Larry Bretthorst, Kevin J. Black

Kevin J. Black, MD

Background: This study’s goal was to provide dose-response data for a dopamine agonist in the baboon using standard methods (replicate measurements at each dose, across a range of doses), as a standard against which to subsequently validate a novel pharmacological MRI (phMRI) method. Dependent variables were functional MRI (fMRI) data from brain regions selected a priori, and systemic prolactin release. Necessary first steps included estimating the magnitude and time course of prolactin response to anesthesia alone and to various doses of agonist. These first steps (“time course studies”) were performed with three agonists, and the results were used to select …

Welcome To The Journal Of Evolution And Health, Aaron Blaisdell, Paul Jaminet, David C. Pendergrass

Aaron P Blaisdell

Welcome to the first issue of the Journal of Evolution and Health! The Journal of Evolution and Health is the peer-reviewed, open-access journal of the Ancestral Health Society, a community of scientists, healthcare professionals, and laypersons who collaborate to understand health challenges from an evolutionary perspective.

Seizure Protection By Intrapulmonary Delivery Of Midazolam In Mice, Ashish Dhir, Dorota Zolkowska, Michael A. Rogawski

Michael A. Rogawski

The lung provides a portal of entry that could be used to rapidly deliver anticonvulsant substances to the brain to treat seizures. In the present study, we demonstrate that midazolam, a water-soluble anticonvulsant benzodiazepine, confers potent seizure protection when administered via the intrapulmonary route. High dose (100 mg/kg) intraperitoneal midazolam induced loss-of-righting reflex in mice. Lower doses of midazolam (100–1000 μg/kg) when administered intraperitoneally did not induce loss-of-righting reflex but protected animals against pentylenetetrazol (PTZ)-induced seizures. Intrapulmonary administration of midazolam via a tracheal cannula protected against intraperitoneal PTZ seizures at lower doses. The minimal intraperitoneal and intravenous doses of midazolam …

Long-Lasting Attenuation Of Amygdala-Kindled Seizures After Convection-Enhanced Delivery Of Botulinum Neurotoxins A And B Into The Amygdala In Rats, Maciej Gasior, Rebecca Tang, Michael A. Rogawski

Michael A. Rogawski

Botulinum neurotoxins (BoNTs) are well recognized to cause potent, selective and long-lasting neuroparalytic actions by blocking cholinergic neurotransmission to muscles and glands. There is evidence that BoNT isoforms can also inhibit neurotransmission in the brain. Here we examined whether locally delivered BoNT/A and BoNT/B can attenuate kindling measures in amygdala-kindled rats. Male rats were implanted with a combination infusion cannula-stimulating electrode assembly into the right basolateral amygdala. Fully-kindled animals received a single infusion of vehicle or BoNT/A or BoNT/B at doses of 1, 3.2, or 10 ng over a 20-min period by convection enhanced delivery (CED). Electrographic (EEG) and behavioral …

Issues Related To Development Of New Antiseizure Treatments, Karen S. Wilcox, Tracy Dixon-Salazar, Graeme J. Sills, Elinor Ben-Menachem, H. Steve White, Roger J. Porter, Marc A. Dichter, Solomon L. Moshe, Jeffrey L. Noebels, Michael D. Privitera, Michael A. Rogawski

Michael A. Rogawski

This report represents a summary of the discussions led by the antiseizure treatment working group of the International League Against Epilepsy (ILAE)/American Epilepsy Society (AES) Working Groups joint meeting in London (London Meeting). We review here what is currently known about the pharmacologic characteristics of current models of refractory seizures, both for adult and pediatric epilepsy. In addition, we address how the National Institute of Neurological Disorders and Stroke (NINDS)-funded Anticonvulsant Screening Program (ASP) is evolving to incorporate appropriate animal models in the search for molecules that might be sufficiently novel to warrant further pharmacologic development. We also briefly address …

Microbes In Pool Filter Backwash As Evidence Of The Need For Improved Swimmer Hygiene — Metro-Atlanta, Georgia, 2012, Christopher Hutcheson, Ryan Cira, Stanley L. Gaines, Kevin R. Jones, Walter Howard, David Hornsby, Maurice Redmond, R. Christopher Rustin, Michele C. Hlavsa, Jennifer L. Murphy, Jothikumar Narayanan, Candace D. Miller, Brittany Cantrell, Vincent R. Hill, Michael J. Beach

R. Christopher Rustin

A Discourse On The Public Nature Of Research In Contemporary Life Science: A Law-Policy Proposal To Promote The Public Nature Of Science In An Era Of Academia-Industry Integration, Michael J. Malinowski

Michael J. Malinowski

This article addresses the impact of integration of academia, industry, and government on the public nature of research. The article concludes that, while the integration has benefited science immensely, regulatory measures should be taken to restore the public nature of research in an age of integration.

Ecosystems And Human Health:Toxicology And Environmental Hazards, Richard Philp

Richard B. Philp

This is a teaching text covering the toxicology of pollutants such as heavy metals and persistent organic pollutants, pesticides, as well as of animal and plant venoms and toxins. Environmental disasters are discussed and updated. There numerous case studies and each chapter has a self-evaluation quizz. See also www.amazon.com/Ecosystems-Human-Health-Toxicology-Environmental/dp/146656721

A Thousand Tiny Pieces: The Federal Circuit’S Fractured Myriad Ruling, Lessons To Be Learned, And The Way Forward, Jonathan R. K. Stroud

Jonathan R. K. Stroud

No abstract provided.

Could You Repeat That Please? Forty-Five Years Of Testing Pesticides On People, Barbara R. Leiterman Esq.

Barbara R. Leiterman Esq.

Little has been published in the literature about pesticide experiments conducted on human subjects. Yet there were at least twenty-two tests between 1967 and 2011 in which people were intentionally exposed to specific doses of pesticides. Almost all of these experiments violated scientific ethics and human rights. This article aims to describe those tests and their shortcomings, and explore the laws and regulations that incentivize such human experimentation. Ironically, as the public desire for pesticide safety increases, so does the industry’s motivation to test pesticides on people. Bringing these pesticide experiments to light, expanding the public discourse on the subject …

The Intrinsic Severity Hypothesis Of Pharmacoresistance To Antiepileptic Drugs, Michael Rogawski

Michael A. Rogawski

Pharmacoresistance to antiepileptic drugs (AEDs) is a barrier to seizure freedom for many persons with epilepsy. For nearly two decades, pharmacoresistance has been framed in terms of factors affecting the access of AEDs to their molecular targets in the brain or the actions of the drugs on these targets. Shortcomings in this prevailing view led to the formulation of the intrinsic severity hypothesis of pharmacoresistance to AEDs, which is based on the recognition that there are neurobiologic factors that confer phenotypic variation among individuals with etiologically similar forms of epilepsy and postulates that more severe epilepsy is more difficult to …