PACE UNIVERSITY
Memorandum
From: Dr. David M.A. NabiRahni
Professor of Chemistry, Pleasantville
Adjunct Professor, Environmental Law, Pace-WP
To: Whomever it May Concern
Subject: Sabbatical Report 2002
PREAMBLE:
For the 2002 sabbatical leave, I served as the Senior Medical Research Associate in Professor Patricia Ann Broderick’s Neuroscience Laboratory, situated at the Pharmacology and Physiology Department in the CUNY Medical School, Harlem New York 10031; the work was also in collaboration with Neurology/Neurosurgery Colleagues from NYU-Mount Sinai School of Medicine and colleagues from Codman/Johnson & Johnson based in Switzerland. I collaborated on, and led projects that could be broadly defined as “Neuro-psycho-electro-analytical pharmacology.” Specifically, I developed a series of electro-analytical chemical methods and biosensors devices for in vitro, ex vivo/in situ and in vivo assays of key neurotransmitters and related analytes, namely, dopamine, serotonin, tryptophan, glutamate, nitric and nitrous oxides, homovanilic acid, epinephrine and norepinephrine as key markers of neuro-degenerative or anti-psychotic diseases. I also engaged actively in the micro-/nano-engineering electrode design and manufacturing schemes, and in animal surgical, perfusional, histological and pathological protocols. My other ole was to manage the daily activities of our laboratory that included personnel, material, safety, protocol, etc. The analytical and probing techniques we extensively developed and employed were: cyclic and linear microvoltammtery, amperometry, surface enhanced raman spectroscopy, microscopy, spectroelectrochemistry, infra red computer based behavioral cage monitoring and analyses, and in drugs (e.g., cocaine), agonist and antagonist administration, pre-/post-synatic dtermination of drug effects, pharmacokinetics and action mechanism. My sabbatical leave once again tuned out to be an outstanding period of learning, sharing and contributing, thereby surpassing my super productive prolific first sabbatical leave 1993-1994 when I served as a T.J. William Fulbright Senior Research School in Manufacturing Engineering at the Technical University of Denmark, followed then by a visiting professorship at the University of Oxford, UK. No less than half- dozen presentations, proceedings and publications are imminently anticipated based on my 2002 leave. I also continued my professional activities with the Am. Chem. Soc. As a Councilor-alternate, editorial board membership with the FBI’s Forensic Science Communications , Fulbright Senior specialists and senior Fulbright reviewer for the Scandinavian Countries, etc. My serving as a Board Member for the Federated Conservationists of Westchester, and my nomination to the County Board of Legislators for the Pest Control Committee as well as serving on numerous Persian American Civil Rights and Community Organizations nationwide are among other pro bono endeavors.
READING:
I.Literature Search:
Based on a series of comprehensive informational searches of data banks comprised of Biological and Chemical Abstracts services, Library of Medicine, Index Medicos, Lexis-Nexis/Westlaw, etc., selected Journal articles and abstracts of over 15,000 were downloaded and saved. These were then closely investigated with particular emphases on the specific articles dealing with assay, effects and drug based modulation of neurotransmitters in specific brain components (e.g., hippocampus, nucleus accumbens, dentate gyrous, amygdala, frontal cortex, brain gray and white matters and their sub-parcelations), micro-(bio-) sensors, neurological mechanism and receptors, addiction, behavior, and with particular emphasis on device bio-implantation, neuropsychiatric and other diseases like epilepsy, schizophrenia, depression, mood change, Parkinson’s, Alzheimer’s, cognitive neurobiology and so on. The acquisition and careful examination of seven hundred manuscripts to further contribute toward the field was the outcome of such massive search and reading.
II.Periodicals and journals:
The following periodicals received in the laboratory were routinely scanned for possible new findings pertinent to our on going research endeavors:
Journal of the Electrochemical Society
Journal of Clinical Neurophysiology
Biological Psychiatry
Epilepsia
Brain Research
Analytical Biochemistry
Analytical Chemistry
American Genomic/Proteomic Technology
Science (AAAS)
Chemical and Engineering News
InfoJustice, published by the Am. Soc. For Justice Through Science (Honorary Fellow)
Journal of Forensic Identification
American Scientist (Sigma Xi)
Neuro-psycho-pharmacology
Journal of Psychiatry
III. Books Read:
-Neuropsyhopharmacology
-Voltammetric Methods in Brain Systems
-Neurotrophic Factors
-Glutamate and Addiction (Humana 2002)
-Animal Models in Psychiatry
-The Neuronal Microenvironment
-The Biochemical Basis of Neuropharmacology
-The Neural Science by the Nobel Laureate Kendall et al of Columbia U (1600 pages +)
-Epilepsy: A Comprehensive three-volume (3000+ pages) Textbook
Editors: Jerome Engel, Jr. and Timothy A. Pedley
-Microbiology: A Lippincott’s Illustrated Review, Richard A. Harvey and Pamela A. Chemyse (2001).
-The Kyoto Protocol and the International Trade and Investment Regimes, Ed W. Bradnee Chambers, UN Press 2001
-Neurosteroids and Brain Function, Ed Giovanni Biggio and Robert H. Purdy, I. –
-International Review of Neurobiology 46 (2001), Academic Press.
-Biomedical Engineering and Devices: Human Application Ed Donald Wise et al Humana Press (2000).
-Learn form numerous sources about Drugs, mechanistic effects and the specific brain receptors/locations.
-Neurobiology of Stereotyped Behavior, SJ Cooper & CT Dourish, Oxford Press
-Medical Drug Reference (1998 Mosby) and PDR Reference.
PROPOSALS
Assisted as co-investigator, Dr. Broderick in the following grant proposals:
On Glutamate sensor (CUNY PSI) $25K
On (NIH-SCORE) $700,000 submitted February 1, 2002
On in vivo sensors for dopamine and Seretonin (Johnson’s and Johnson’s) 100K
On epileptic drug study and their effects on neurotransmitters, for Epilepsy Foundation $50K
Cultured relationships with several government and non-for-profit organizations including NIH, Epilepsy Foundation, and Michel J. Fox Foundation for Parkinson’s disease (a letter of intent submitted).
SCHOLARLY PROJECTS
Electrode fabrications (I, J, R, S and K micro-voltammetric Indicator Sensors, macro and micro-chronic and acute references, and auxiliary, anchors, shams)
Animal surgery, perfusion, histology and pathology techniques
Animal electrode assembly implantation
Animal Behavioral studies under cocaine, agonist and antagonist effects of risperidone, clozapine and ketanserin.
I.Implantable sensors worked on:
(Dopamine, Seretonin, Acetyl choline, Glutamate, Nitrous oxide, Nitric oxide among others) so as to optimize the sensitivity, stability and linear dynamic range for each while minimizing potential interference response against protein and fat fouling effect, ascorbic acid, drugs and their metabolites, ethanol, acetone, etc.
II. Publications and Presentations:
RISPERIDONE, DAD2/5 - HT2 ANTAGONIST, BLOCKS COCAINE - INDUCED DOPAMINE ( DA ) AND SEROTONIN ( 5 - HT ) RELEASE IN NUCLEUS ACCUMBENS NACC ) DURING LOCOMOTION IN A REAL - TIME in vivo MICROVOLTAMMETRIC STUDY P.A.Broderick1,2*; Y.Zhou1; D.N.Rahni1,3 1. Physiology & Pharmacology, CUNY Medical School, New York, NY, USA; 2. Neurology, NYU School of Medicine & NYU-Mount Sinai Comprehensive Epilepsy Center, New York, NY, USA; 3. Chemistry & Physical Sciences, Pace University, Pleasantville, NY, USA Society for Neuroscience National Meeting (Two Papers), November 1-8, 2002 Orlando, FL
We continue to study treatment modalities for cocaine-induced psychosis. Of particular interest to us, are the atypical ant psychotic drugs. Risperidone was selected for study because it has a pharmacological profile similar to that of clozapine (Marcus, Neuropsychopharmacol. 6, 1996), although it has an affinity for DAD2/5-HT2 receptors which is less than that for clozapine(Gudelsky,1998). Thus, we determined the effect of risperidone,(2 mg/kg,sc)(n=4) on cocaine (10 mg/kg, ip)-induced 5-HT and DA release in NAcc using in vivo microvoltammetry WHILE locomotion was assayed with infrared photo beams. BRODERICK PROBE , Lauric and Stearic Acid microelectrodes were stereotaxically implanted in NAcc (Pellegrino et al. 1979); Ag/AgCl reference and stainless steel auxiliary microelectrodes were placed in contact with dura. Results showed that risperidone blocked the expected increase in 5-HT release that occurs after cocaine;DA release was also blocked but signals reverted to above baseline in about one hour. Locomotion was attenuated as well. The next day, without further injection of either risperidone or cocaine, 5-HT was increased while DA stayed at control or below, locomotion reverted back to exploratory levels.The enhanced 5-HT effect maintained at the 24th hour, may help alleviate depression known to be associated with cocaine withdrawal. Supported by: Pace U. Kenan & Sabbatical Funds, PSC/CUNY & NIH NIGMS S06 GM08168.
Program Number: 399.5Day / Time: Monday, Nov. 4, 1:00 PM - 2:00 PM
- Program Number: 828.15Day / Time: Thursday, Nov. 7, 10:00 AM - 11:00 AM A NOVEL MICROVOLTAMMETRIC APPROACH FOR THE DETERMINATION OF NITROUS AND NITRIC OXIDES: HUMAN EPILEPSY D.N.Rahni1,3*; S.V.Pacia2; P.A.Broderick1,3 1. Physiology & Pharmacology, CUNY Medical School, New York, NY, USA; 2. Neurology, NYU School of Medicine & NYU-Mount Sinai Comprehensive Epilepsy Center, New York, NY, USA; 3. Chemistry & Physical Sciences, Pace University, Pleasantville, NY, USA There is an increasing need and merit for a novel sensor that could simultaneously determine in vivo the concentrations of key neurotransmitters and gases such as nitrous(N2O)and nitric(NO)oxides. Recognized as a neurotransmitter, NO, ranking among the most significant endogenous vasodilators, plays a key role in the manifestation of delayed vasospasm in patients with subarachnoid hemorrhage(Khaledi Neurosurg 49 2001). Furthermore,(N2O),presumably synthesized in ultra low concentrations by the body if any, or when administered as a secondary anesthetic gas, is of extreme significance for intraoperative monitoring of brain. Crespi has reported a pulse method for the measurement of NO and nitrites(J Neurosci. Methods 2001). We propose herein a voltammetric method employing a BRODERICK PROBE for the assay of NO and N2O, in conjunction with Ag/AgCl reference and stainless steel auxiliary microelectrodes. The electrode assembly was placed under ambient condition in a physiological phosphate buffer system, pH 7.40. The anodic sweep current amplitude, measured at dual signals of 80/+750 mV, and at +530 mV, corresponded to NO and N2O effective concentrations, respectively. Moreover, the Voltammogram exhibited distinct responses at previously reported potentials for Dopamine(+120 mV), Serotonin (+280 mV), and Tryptophan (+670 mV)(Broderick,Handbook Neurotox.2 2001). Application to human epilepsy will be presented. Supported by: Pace U. Kenan & Sabbatical Funds, Parents Against Childhood Epilepsy, PSC/CUNY&NIH NIGMS S06 GM08168. Citation: D.N.Rahni, S.V.Pacia, P.A.Broderick. A NOVEL MICROVOLTAMMETRIC APPROACH FOR THE DETERMINATION OF NITROUS AND NITRIC OXIDES: HUMAN EPILEPSY. Program No. 828.15. 2002 Abstract Viewer/Itinerary Planner. Washington, DC: Society for Neuroscience, 2002. CD-ROM.
- Neurotransmitter Signatures: A Comparison of Microvoltammetric BRODERICK PROBES®vs. Raman Spectroscopy
Foucault, R; Broderick, PA*; Rahni , D.N*§; Lombardi, J.R and Birke, R.L
The City College of New York and the CUNY Graduate Center, NY 10031
* Department of Physiology and Pharmacology, The CUNY Medical School, New York NY 10031
§Department of Chemistry, Pace University, Pleasantville NY 10570-2799
Abstract
Microvoltammetric electro-analytical and Raman spectroscopic techniques were developed to decipher insights into the mechanism of brain neurotransmitters especially dopamine (3-Hydroxytyramine) and serotonin (5-Hydroxytyramine) in an in-vitro experiment. We have monitored the within day-to-day response to dopamine and serotonin by mimicking brain in an electrochemical cell with the BRODERICK PROBE®. J or K BRODERICK PROBE® were utilized to compare sensitivity, selectivity and stability toward dopamine and serotonin as a function of preconditioning. When placed in different media such as plain phosphate buffer, 10% bovine serum albumin (BSA), 10% phosphatidylethanolamine (PEA) and 10%PEA 1% BSA combination, it has been observed that both types of electrodes have exhibited minimal response vis–a–vis these neurotransmitters in the presence of 10% bovine serum albumin (BSA) pre-conditioning, while they tend to have an enhanced response and selectivity in a 10% PEA 1% BSA combination. In addition, in a mixture of 10 % PEA and 10% BSA, the J PROBE has shown a split for the dopamine peak while the serotonin peak has not shown any splitting. Thus, we conclude that relatively large proteins, albeit bovine serum albumin (BSA) can greatly interfere with the response of the BRODERICK PROBE® toward the neurotransmitters (DA & 5-HT) by binding quasi-reversibly on the electrode surfaces, thereby preventing the otherwise anticipated electron transfer between the BRODERICK PROBE® and the analytes of interest. Furthermore, a comparison of the Raman spectra of these neurotransmitters can assist us gain insight in their structure-receptor relationships.
R.L.NIH/NIGMS ABRCMS National Symposium, Hyatt Regency, November 13-16, 2002 New Orleans, LA 70122
-Anthrax Insights, a comprehensive article in Journal of Forensic Identification, 2002: Vol. 52, 84-92.
-Numerous writings and interviews on policies and non-science related topics including one interview (Monday Sept 30) with the BBC’s World News service.
-Understanding Anthrax, Info Justice Journal March 2002.
-Helped organize and will Preside over the BIOELECTROCHEMISTRY Symposium at the Pittsburgh Conference, Orlando, FL March 9-15, 2003.
- Music Rules, an article on Greg Aslani, the renowned Persian-American Musician
Also a modified version appeared in Parastoo Vol 14, No. 2, 2002, and
III. Honors and Professional/Community Service:
-Continued serving as an editorial board member, for the FBI’s Forensic Science Communications.
-Recognized with appreciation as the Judge for the presentations at the 30th Annual Biomedical Research Conference for Minority Students, sponsored by the NIH-NIGMS New Orleans, Nov. 13-17, 2002.
-Inducted as Honorary Fellow in the “American Society for Justice Through Science”
-Monthly meeting, Board Member, Federated Conservationists of Westchester
-Bimonthly meeting, Gala and Fund raising Committee of FCWC
-Member, Pest Management Committee (to be Approved by the County Legislators and appointed by the County Executive)
-ACS Nichols Jury Meetings, 2002, ACS NY
-ACS Nichols Symposium and Banquet March 22, Crowne Plaza 2002
-ACS NY Fundraising Committee
-Intel/WESTEF Science mentorship (mentored Ernie Homsy on Fuel Cells Research, Mamaroneck High School currently an engineering freshman at St. Louis University) and served as a judge for the 120 + research presentations on March 16, 2002 at Pace.
-Have attended 1-2 weekly seminars at CUNY Medical School, CCNY-Harlem and the CUNY Graduate Center, New York, ACS ranging from engineering, medical, natural, physical sciences to foreign policy topics (~100 in 2002).
-Urban University Conference at CCNY Harlem
Keynote Speaker: Rita Collwell, NSF Director
-Community Stakeholder/Technical Advisor with/for EPA Facilitator David Bidwell
Hudson River PCB Mitigation Project May 6, 2002
-Treatment of Psychotic Disorders: What is the State of the Art? (participant)
Activation participation with less than 100 other mostly clinical psychiatrists at a two-day conference Grand Hyatt Hotel, New York (July 12-13, 2002) to listen to 20 of the most famous mostly MD and MD/PHD peers in the filed and debate the field.
-Was interviewed by ISNA three times on the comparative status of the chemical academic and research sciences in Iran, and on the sustainable development: a comparative assessment of the third world and the developed countries.
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