| Development of a Guinea Pig Model for Low-Dose Chronic Exposure to Organophosphorus Nerve Agents |
MAY 2003 |
34 pages |
| Authors:
Chessley R. Atchison; Robert E. Sheridan; Steven M. Duniho; Tsung-Ming A. Shih; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
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 | An animal dosing model and related maximum tolerated dose (MTD) were developed for repeated exposures in guinea pigs to three organophosphorus chemical warfare nerve agents (CWNA). Male animals were injected subcutaneously with sarin (GB), soman (GD) or VX once a day (Monday through Friday) for 2-, 4-, or 13-weeks. An initial 13-week study for each CWNA employed doses of vehicle (normal saline), 0.2, 0.4, 0.6, and 0.8 x the previously ... |
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| Control of Nerve Agent-Induced Seizures is Critical for Neuroprotection and Survival |
AUG 2002 |
28 pages |
| Authors:
Tsung-Ming A. Shih; Steven M. Duniho; John H. McDonough; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
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| The effectiveness of some anticholinergics (atropine, biperiden or trihexyphenidyl) and beazodiazepines (diazepam or midazolam) as an anticonvulsant treatment against seizures induced by six nerve agents (tabun, sarin, soman, cyclosarin, VR and VX) was studied in a guinea pig model that closely approximates the use of pretreatment and therapy drugs as medical countermeasures for nerve agent exposure. The time to seizure onset, the time to seizure termination, and 24-h lethality were ... |
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| Time-Course Effects of GA, GB, GD, GF and VX on Spinal Cord Cholinesterase and Acetylcholine Levels in Six Discrete Areas of the Rat Brain |
JAN 2001 |
28 pages |
| Authors:
Bernard J. Benton; John H. McDonough; Thomas A. Koviak; Tsung-Ming A. Shih; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
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| The time-course changes of spinal cord cholinesterase (ChE) and acetylcholine (ACh) levels in six discrete regions of the rat brain were studied and compared. Rats were injected subcutaneously with a 0.9 LD50 dose of GA, GE, GD, GF or VX. They were observed for symptoms of intoxication and head-focused microwave irradiated at 10 time points ranging from 5 minutes to 24 hours after compound administration. Brain tissue samples were homogenized ... |
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| Anticonvulsant Actions of Anticholinergic Drugs in Soman Poisoning |
FEB 91 |
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| Authors:
Tsung-Ming A. Shih; Benedict R. Capacio; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
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 | The acute effects of organophosphorus cholinesterase inhibitor soman include hypersecretions, convulsions, and death. The purpose of this study was to evaluate the anticholinergic compounds aprophen, atropine sulfate, azaprophen, benactyzine, benztropine, biperiden, scopolamine HBr, and trihexyphenidyl for their efficacy in preventing soman-induced hypersecretions and convulsions. Male rats were injected with the oxime HI-6 (125 mg/kg, ip), to increase survival time, along with various intramuscular (im) doses of the anticholinergics 30 min ... |
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| Cerebral Blood Flow-Metabolism Coupling After Administration of Soman at Non-Toxic Levels |
FEB 91 |
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| Authors:
Tsung-Ming A. Shih; Oscar U. Scremin; Kevin D. Corcoran; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
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| The effects of soman, a potent organophosphorus cholinesterase inhibitor, on regional cerebral blood flow and glucose utilization were studied with a double tracer, autoradiographic technique in rats. Soman was given at a sub-toxic dose of 55 ug/kg s.c. and variables were measured 45 min later. No changes in arterial blood pressure or signs of toxicity were present in the animals studied. Soman induced a pronounced increase in cerebral blood flow. ... |
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| Anticonvulsant Effects of Diazepam and MK-801 in Soman Poisoning |
MAY 90 |
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| Authors:
Tsung-Ming A. Shih; Thomas A. Koviak; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
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| An animal model was developed to evaluate the anticonvulsant effects of diazepam and MK-801 in soman poisoning and to examine the possible mechanism of soman-induced convulsions. The oxime HI-6 (125 mg/kg, ip) was given to male rats, to increase survival, 30 min prior to 180 ug/kg, sc, (equivalent to 1.6 x LD50) of soman, which produced 100% occurrence of convulsions. Initially, diazepam was studied with or without the concomitant administration ... |
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| Effects of Soman and Sarin on High Affinity Choline Uptake by Rat Brain Synaptosomes |
DEC 88 |
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| Authors:
Christopher E. Whalley; Tsung-Ming A. Shih; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
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| Synaptosomes were incubated at various time intervals following injection of 120 ug/kg sc of soman or sarin or with various concentrations of soman or sarin in vitro. Total cholinesterase (ChE) activities in each brain region were also measured. Following soman injection, sodium-dependent, high affinity choline uptake (SDHACU) was decreased from 1 to 4 h in the cortex and from 1 to 2 h in the hippocampus, but increased from 2 ... |
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| Comparison of Cholinergic Effects of HI-6 and 2-PAM in Soman Poisoning |
OCT 88 |
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| Authors:
Tsung-Ming A. Shih; Christopher E. Whalley; James J. Valdes; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
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| Recently, the oxime HI-6 when combined with atropine sulfate (ATS) has been reported to be effective against soman poisoning. We compared the effects of HI-6 and a standard oxime pralidoxime chloride (2-PAM) on soman- induced lethality, time to death and several cholinergic parameters in rats to understand the beneficial action or HI-6. Treatment with ATS or HI-6 alone protected against 1.2, and 2.5 LD50s of soman respectively, whereas 2-PAM or ... |
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| Hormonal Rhythms Two Weeks Post-Exposure to a Single Dose of Soman |
AUG 87 |
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| Authors:
Tsung-Ming A. Shih; G. J. Kant; John R. Leu; Thomas G. Raslear; Edward H. Mougey; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
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| Two weeks following a single exposure to either soman (100 ug/kg., s. c.) or saline, rats were sacrificed at two-hour intervals over a 24-hour period. Trunk blood was collected and plasma was stored until assayed for corticosterone, prolactin, growth hormone, adrenocorticotropin (ACTH) beta- endrophin and beta-lipotropin (beta-LPH). Rats surviving for two weeks following soman appeared well groomed and were gaining weight at a rate similar to saline- treated rats at ... |
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| Effects of Repeated Injection of Sublethal Doses of Soman on Behavior and on Brain Acetylcholine and Choline Concentrations in the Rat |
JUN 87 |
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| Authors:
Tsung-Ming A. Shih; David E. Lenz; Donald M. Maxwell; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
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| The effects of repeated administration of soman (60 ug/kg; 0.4 LD 50) on brain regional acetylcholine (ACh) and choline (Ch) levels and on water consumption, body weight and gross behavioral changes were examined. Rats were dosed once a week or three times a week and selected brain tissue examined at 24 hr after 2, 4 or 6 weeks of chronic dosing. During the 6-week period, there was no difference between ... |
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| Age-Related Changes in Cholinesterase Activity and Soman Toxicity in the Rat |
MAY 87 |
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| Authors:
Tsung-Ming A. Shih; David M. Penetar; John H. McDonough; James A. Romano Jr.; James M. King; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
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| Plasma and brain regional cholinesterase (ChE) activity profiles and the toxicity (lethality, acute toxic signs and body weight loss) of the irreversible ChE inhibitor soman (pinacolyl methylphosphonofluoridate) were assessed in four groups of male rats differing in age: 30, 60, 120 and 240 days old. Plasma ChE did not change significantly with age. Brain regional ChE activity showed two distinct age-dependent patterns: a linear decrease in the brainstem, midbrain and ... |
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| Effects of Diazepam and Atropine Sulfate on Soman-Induced Convulsions and Elevation of Brain Acetylcholine and Choline Concentrations |
MAY 87 |
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| Authors:
Tsung-Ming A. Shih; ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD
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| Soman, an organophosphorus cholinesterase (ChE) inhibitor, was used to induce blood and brain ChI inhibition, to elevate brain acetylcholine (ACh) and choline (Ch) concentrations and to produce convulsions in rats. The effectiveness of diazepam in reversing these effects in the presence or absence of atropine sulfate was studied. Diazepam blocked the convulsive activity of soman whereas atropine sulfate did not. Neither diazepam nor atropine sulfate alone affected ChE activity, nor ... |
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