| Sensitive and Rapid Blood and Tissue HPLC Oxime Assay and Pharmacokinetics of MMB-4 in Guinea Pigs and African Green Monkeys |
NOV 2006 |
8 pages |
| Authors:
Gregory E. Garcia; Harry Singh; Deborah Moorad-Doctor; Ruthie H. Ratcliffe; Katie Wachtel; Andres Castillo; Richard K. Gordon; Todd M. Myers; John H. McDonough; WALTER REED ARMY INST OF RESEARCH SILVER SPRING MD
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 | We developed a rapid and sensitive assay for pyridinium oximes in plasma and tissues. Samples are prepared by acidification and then deproteinized by ultrafiltration. The oximes are measured during sample HPLC fractionation over a cation-exchange column with UV detection. The assay is suitable for analysis of mono- and di-pyridinium oximes, but was originally developed for the measurement of the oxime MMB-4. For both plasma and tissue sources, the LLOD was ... |
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| Detoxification of Chemical Warfare Agents by the Plant Cholinergic System |
01 OCT 2005 |
7 pages |
| Authors:
Suman S. Thakur; Gregory E. Garcia; Haim N. Leader; Deborah Moorad-Doctor; Rajendra Gupta; Richard K. Gordon; Bhupendra P. Doctor; WALTER REED ARMY INST OF RESEARCH SILVER SPRING MD
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| Plants have cholinesterases (pChEs), anti-ChEs, and activators of ChEs. We have isolated pChE from mung bean sprout. We investigated 300 plants and found that 75% of them contained anti- ChE that inhibited ChEs. Thirty-five percent contained activators of ChEs. An activator of ChE from wheat leaf, Tritiacche-T123 , activates fetal bovine serum AChE, equine BChE, and pChE. This non-oxime natural plant product may offer a new approach to the reactivation ... |
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| Transcriptional Inducers of Acetylcholinesterase Expression as Novel Antidotes for Protection Against Chemical Warfare Agents |
01 OCT 2005 |
19 pages |
| Authors:
Bryan F. Curtin; Lauren M. Tetz; Richard K. Gordon; Bhupendra P. Doctor; Madhusoodana P. Nambiar; WALTER REED ARMY INST OF RESEARCH SILVER SPRING MD
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| The biological effects of organophosphorous chemical warfare agents (CWAs) are exerted by inhibition of acetylcholinesterase (AChE), which blocks the hydrolysis of acetylcholine leading to hypercholinergy, seizures, status epilepticus, respiratory/ cardiovascular failure and death. Current investigations show that bio-scavenger therapy, using purified fetal bovine AChE and the more recently tested human BChE, is a promising treatment for protection against CWA exposure. Impediments such as the complex structure of AChEs, posttranslational modifications, ... |
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| Real Life Experiences Using the WRAIR Whole Blood and Pyridostigmine Assays |
01 OCT 2005 |
12 pages |
| Authors:
Julian R. Haigh; Gregory E. Garcia; Deborah R. Moorad-Doctor; Marian S. Farah; Bhupendra P. Doctor; Shawn R. Feaster; Richard K. Gordon; David E. Lenz; Connie R. Clark; Michael A. Riel; WALTER REED ARMY INST OF RESEARCH SILVER SPRING MD
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| Walter Reed Army Institute of Research Whole Blood (WRAIR WB) cholinesterase assay rapidly determines the concentrations of both AChE and BChE in unprocessed whole blood, uses a minimally invasive blood sampling technique (finger prick), and is fully automated (using the Biomek 2000 robotic system). In human blood from volunteers given pyridostigmine bromide (30 mg single dose), RBC-AChE was maximally inhibited by about 30% after 2.5 h, with recovery to 95% ... |
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| Selective Binding of Organophosphate Pesticides Using Molecular Imprinted Polymers |
01 OCT 2005 |
7 pages |
| Authors:
Ali M. Saboori; Richard K. Gordon; WALTER REED ARMY INST OF RESEARCH SILVER SPRING MD
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| Molecular Imprinted Polymers (MIPs) have been used for recognition and binding of different compounds. We are developing MIPs to selectively bind organophosphate pesticides and toxic chemical warfare nerve agents. MIPs were made to the pesticide Dichlorvos. Control MIPs were made without the template. Dichlorvos-MIPs bound more Dichlorvos in comparison to control-MIPs. The Dichlorvos-MIPs can be regenerated after binding the pesticide and reused at least three times by repeating the washing ... |
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| Development of a Rat Diisopropylfluorophosphate-Induced Seizure/Status Epilepticus Model for Screening of Neuroprotectants Following Exposure to Chemical Warfare Agents |
17 NOV 2004 |
17 pages |
| Authors:
Stacy M. Crawford; Jaimee R. Compton; Lauren M. Tetz; Ruthie H. Ratcliffe; Keith H. Steele; Richard K. Gordon; Madhusoodana P. Nambiar; WALTER REED ARMY INST OF RESEARCH SILVER SPRING MD
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| We have developed a seizure/status epilepticus (SE) rat model using diisopropylfluorophosphate (DEP), an organophosphate (OP) surrogate for chemical warfare nerve agents (CWNA) soman and sarin. Rats were surgically implanted with a radiotelemetry probe that records EEG, ECG, body temperature, and physical activity. After 1 week they were exposed to various concentrations of DFP (1.5-4.0 mg/kg, sc) in the presence of pyridostigmine bromide, 2-PAM and atropine to produce more than 24 ... |
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| Adenosine Receptor Agonist Pd 81,723 Protects Against Seizure/Status Epilepticus and Neuropathology Following Organophosphate Exposure |
17 NOV 2004 |
17 pages |
| Authors:
Jaimee R. Compton; Stacy M. Crawford; Ruthie H. Ratcliffe; Keith H. Steele; Richard K. Gordon; Madhusoodana P. Nambiar; WALTER REED ARMY INST OF RESEARCH SILVER SPRING MD
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| A novel approach to broad-specificity medical countermeasure against chemical warfare nerve agent (CWNA) poisoning is by preventing excessive accumulation of ACh attributable to AChE inhibition of CWNA exposure. The effectiveness of various partial adenosine A1 receptor agonists as post-CWNA exposure (1 hour) neuroprotectants was investigated in the study using a rat seizure/status epilepticus model that employs the organophosphate diisopropylfluorophosphate, a surrogate comparable to the nerve agent soman. Physiological data collected ... |
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| Forskolin, an Inducer of Camp, Up-Regulates Acetylcholinesterase Expression and Protects Against Organophosphate Exposure in Neuro 2A Cells |
16 NOV 2004 |
12 pages |
| Authors:
Nabaneeta Pal; Bryan F. Curtin; Jaimee R. Compton; Richard K. Gordon; Madhusodana P. Nambiar; WALTER REED ARMY INST OF RESEARCH SILVER SPRING MD
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| Bioscavenger prophylactic therapy using purified human acetylcholinesterase (AChE) or butylcholinesterase (BChE) is a promising treatment for future protection against chemical warfare agent (CWA) exposure. However, the potential limitations of this approach has led to our investigation of alternative bioscavenger approaches using Forskolin, an inducer of cyclic AMP (cAMP). The optimal dose found for repeated treatment of Forskolin was 12-24 M. Exposure to the organophosphate diisopropylflurophophate (DFP) showed that Forskolin treatment ... |
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| Current Pyridostigmine Bromide and Huperzine A Studies and Future Cholinesterase Screening Using the WRAIR Whole Blood Cholinesterase Assay |
15 NOV 2004 |
11 pages |
| Authors:
Richard K. Gordon; Julian R. Haigh; Gregory E. Garcia; Deborah R. Moorad-Doctor; Marian S. Farah; Ralf Brueckner; Shawn R. Feaster; Bhupendra P. Doctor; David E. Lenz; Connie R. Clark; WALTER REED ARMY INST OF RESEARCH SILVER SPRING MD
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| Cholinesterases are highly polymorphic carboxylesterases that display broad substrate specificity and are involved in the termination of neurotransmission in cholinergic synapses and neuromuscular junctions of the central nervous system (CNS). ChEs are classified as acetylcholinesterase and butyrylcholinesterase according to their substrate specificity and sensitivity to selected inhibitors (Silver, 1974). The concentration of AChE and BChE in blood is potentially a stable biomarker of suppressed and/or heightened central and peripheral nervous ... |
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| Celastrus paniculatus Seed Water Soluble Extracts Protect Against Glutamate Toxicity in Neuronal Cultures From Rat Forebrain |
2004 |
8 pages |
| Authors:
Praful B. Godkar; Richard K. Gordon; Arippa Ravindran; Bhupendra P. Doctor; WALTER REED ARMY INST OF RESEARCH SILVER SPRING MD
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| Aqueous extracts of Celastrus paniculatus (CP) seed have been reported to improve learning and memory in rats. In addition, these extracts were shown to have antioxidant properties, augmented endogenous antioxidant enzymes, and decreased lipid peroxidation in rat brain. However, water soluble extracts of CP seed (CP-WSE) have not been evaluated for their neuroprotective effects. In the study reported here, we used enriched forebrain primary neuronal cell (FBNC) cultures to study ... |
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| On the Construction and Use of Two-Dimensional Wavelet-Like Basis Functions |
NOV 2003 |
9 pages |
| Authors:
W. Elliot Hutchcraft; Richard K. Gordon; MISSISSIPPI UNIV UNIVERSITY DEPT OF ELECTRICAL ENGINEERING
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| An alternative method for generating higher dimensional wavelet-like basis functions is proposed in this paper. One method that has been used was to derive the two-dimensional wavelet-like basis from the two-dimensional traditional finite element basis. However, in this paper, products of one-dimensional wavelet-like functions are used as two-dimensional wavelet-like basis functions. The generation of linear wavelet-like functions is discussed in detail and the use of linear and higher order wavelet-like ... |
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| Badges of Immobilized Enzymes: Detection of Chemical Warfare Agents |
01 JUL 2003 |
10 pages |
| Authors:
Alper T. Gunduz; Bhupendra P. Doctor; Richard K. Gordon; WALTER REED ARMY INST OF RESEARCH WASHINGTON DC DIV OF BIOCHEMISTRY
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| Rapid detection of chemical warfare agents (CWAs) in all of its forms including gas and liquid is of paramount importance to protect the warfighter or first responders in homeland defense. CWAs such as OPs and vesicants pose serious threats because these agents can be ingested with contaminated food or rapidly penetrate skin. We reported that polyurethane immobilized cholinesterases (acetyl and butyryl) yielded a product with similar enzyme activity as soluble ... |
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| WRAIR Protocols for Soldier Status and Readiness to Organophosphate Exposure: Unprocessed Whole Blood Cholinesterase and Pyridostigmine Bromide Quantification |
01 JUL 2003 |
5 pages |
| Authors:
Gregory E. Garcia; Shawn R. Feaster; Deborah R. Moorad; Bhupendra P. Doctor; Richard K. Gordon; Connie R. Clark; J. R. Smith; Brian J. Lukey; Raven E. Reitstetter; WALTER REED ARMY INST OF RESEARCH SILVER SPRING MD
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| Exposure to nerve agents, OPs, pesticides, anesthetics, terrorists' chemical agents, and drugs of abuse such as cocaine, heroin, and some neuro-degenerative disease states selectively reduces AChE and/or BChE activity. Since urban terrorism is on the rise, Federal, State, and local authorities need a reliable, fast, inexpensive method for confirming such an assault to initiate appropriate containment, decontamination, and treatment measures. Thus, we developed a semi-automated medical diagnostic microplate procedure capable ... |
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| Decontamination and Detoxification of Toxic Chemical Warfare Agents Using Polyurethane Sponges |
01 JUL 2003 |
11 pages |
| Authors:
Richard K. Gordon; Alper T. Gunduz; LaTawnya Y. Askins; Simon J. Strating; Bhupendra P. Doctor; Edward D. Clarkson; Larry W. Mitchelree; Brian Lukey; Roy Railer; Susan Schulz; WALTER REED ARMY INST OF RESEARCH SILVER SPRING MD
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| Organophosphorus (OP) nerve agents are some of the most potent toxic agents conceived by mankind, are specific inhibitors of cholinesterase (ChE), and therefore are a serious threat to military and civilian personnel. OP nerve agents can exist as a liquid and contaminate skin, penetrate, resulting in deleterious systemic effects including a cholinergic crisis. Another serious problem that may be encountered while caring for personnel contaminated with organophosphorus chemical warfare nerve ... |
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| Selective, Specific, and Versatile Personal Biosensors to Organophosphate Chemical Toxins Composed of Polyurethane Immobilized Enzymes |
JAN 2002 |
9 pages |
| Authors:
Richard K. Gordon; Alper T. Gunduz; Shawn R. Feaster; Bhupendra P. Doctor; Tracy Cronin; WALTER REED ARMY INST OF RESEARCH WASHINGTON DC DIV OF BIOCHEMISTRY
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| Organophosphorus (OP) nerve agents are a serious threat to military and civilian personnel, so rapid detection of OP compounds in all of these forms is of paramount importance to prevent casualties. Recently, we combined porous polyurethane foam formed in situ from water-miscible hydrophilic urethane prepolymers and enzymes such as ChEs. One of the advantages of this technique imparted to the immobilized enzymes is resistance to denaturing events. Most important, the ... |
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| Decontamination and Detoxification with Sponges |
JAN 2002 |
11 pages |
| Authors:
Richard K. Gordon; Shawn R. Feaster; Alper T. Gunduz; Bhupendra P. Doctor; David E. Lenz; Donald M. Maxwell; Rudy C. Macalalag; Edward D. Clarkson; John P. Skvorak; WALTER REED ARMY INST OF RESEARCH WASHINGTON DC DIV OF BIOCHEMISTRY
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| One of the serious problems that may be encountered while caring for personnel contaminated with organophosphate (OP) chemical warfare nerve agents is the possibility that there will be crosscontamination to the medical personnel. Secondly, during combat or terrorist acts, individuals might be exposed to chemical toxins before they don their protective gear. Therefore, we have attempted to develop an enzyme immobilized polyurethane foam which can effectively decontaminate the skin and ... |
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| Synthesis and Antimuscarinic Activity of 2-(N-(Ethyl)-(N-Beta- Hydroxyethyl)) Aminoethyl 2,2-Diphenylpropionate, a Metabolite of Aprophen |
JUN 1993 |
4 pages |
| Authors:
Nesbitt D. Brown; Haim Leader; Lawrence R. Phillips; Ruthann M. Smejkal; Richard K. Gordon; WALTER REED ARMY INST OF RESEARCH WASHINGTON DC
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| The preparation of 2-(N-(ethyl)-(N-beta-hydroxyethyl)aminoethyl 2,2- diphenylpropionate (1), a metabolite of aprophen 12-diethylaminoethyl 2,2- diphenylpropionate) is described. Hydrolysis of 2-(2-chloroethyl) ethylaminolethyl acetate hydrochloride (2) In a basic solution, followed by acidic pH adjustment, gave the ethylcholineaziridinium ion (3) that upon treatment with 2,2-diphenylpropionic acid produced 1 in a 56% yield. Synthetic 1 was found to possess antimuscarinic activities, but was approx. 10-fold less potent than the parent compound aprophen. |
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