Romano J.A. Chemical warfare agents: toxity at low levels

CHEMICAL WARFARE AGENTS: TOXICITY AT LOW LEVELS......Page 1
Preface......Page 3
Contributors......Page 8
Table of Contents......Page 12
I. INTRODUCTION......Page 14
II. CHRONIC HEALTH EFFECTS OF ACUTE EXPOSURE......Page 18
III. CHRONIC HEALTH EFFECTS OF REPEATED......Page 23
IV. THE CONTRIBUTIONS OF IN VITRO STUDIES......Page 27
V. SUMMARY AND CONCLUSIONS......Page 30
REFERENCES......Page 31
I. INTRODUCTION......Page 38
II. NERVE AGENT STEREOISOMERS: CHIRAL ANALYSIS, ISOLATION, AND TOXICOLOGY......Page 39
III. TRACE ANALYSIS OF NERVE AGENTS IN BIOLOGICAL SAMPLES......Page 43
IV. INTRAVENOUS TOXICOKINETICS OF SOMAN AND SARIN IN VARIOUS SPECIES......Page 46
V. SUBCUTANEOUS TOXICOKINETICS OF SOMAN......Page 55
VI. INHALATION TOXICOKINETICS OF SOMAN AND SARIN......Page 58
VII. INHALATION TOXICOKINETICS OF SOMAN UPON LOW-LEVEL EXPOSURE......Page 65
VIII. ELIMINATION PATHWAYS OF PHOSPHOFLUORIDATES......Page 70
A. ELIMINATION BY HYDROLYTIC DEGRADATION......Page 71
B. ELIMINATION BY COVALENT BINDING......Page 72
C. RENAL EXCRETION......Page 75
D. ELIMINATION PRODUCTS AS TOOLS FOR RETROSPECTIVE......Page 76
IX. PHYSIOLOGICALLY-BASED MODELING OF THE TOXICOKINETICS OF SOMAN......Page 77
X. THE INFLUENCE OF PROPHYLAXIS AND THERAPY UPON THE TOXICOKINETICS OF SOMAN......Page 82
XI. TOXICOKINETICS OF V AGENTS......Page 85
REFERENCES......Page 87
A. NERVE AGENTS......Page 95
B. DELAYED NEUROTOXICITY......Page 97
C. STRESS......Page 101
II. CHOLINERGIC TOXICITY......Page 104
A. BIOCHEMICAL EFFECTS......Page 106
C. CHOLINERGIC TOXICITY UNDER STRESSFUL CONDITIONS......Page 113
III. NON-CHOLINERGIC TOXICITY......Page 115
A. BIOCHEMICAL EFFECTS......Page 116
B. HISTOPATHOLOGICAL EFFECTS......Page 119
IV. SUMMARY......Page 120
REFERENCES......Page 121
CONTENTS......Page 133
II. THE PHYSICAL BASIS OF BLOOD-BRAIN BARRIER PROPERTIES......Page 134
A. ENDOTHELIAL CELLS IN BRAIN VASCULATURE......Page 135
C. POTENTIAL INVOLVEMENT OF ACETYLCHOLINESTERASE......Page 136
D. SIGNAL-TRANSDUCING ELEMENTS......Page 138
A. INWARD AND OUTWARD MOVEMENT ACROSS THE BLOOD-BRAIN BARRIER: PHYSIOLOGICAL CONSIDERATIONS......Page 140
C. PERICELLULAR CELL PASSAGE ACROSS BLOOD-BRAIN BARRIER STRUCTURES......Page 141
D. CELL CULTURE, ORGAN SYSTEMS,  IMAGING APPROACHES IN BLOOD-BRAIN BARRIER RESEARCH......Page 142
E. TRANSGENIC ENGINEERING MODELS FOR BLOOD-BRAIN BARRIER STUDIES......Page 143
IV. MODULATORS OF BLOOD-BRAIN BARRIER FUNCTIONS AND THEIR INTERRELATIONSHIPS......Page 144
B. IMMUNOMODULATORS AND MULTI-DRUG TRANSPORTERS......Page 145
A. PATHOPHYSIOLOGICAL INDUCTION OF BLOOD-BRAIN BARRIER PENETRANCE......Page 146
C. PSYCHOLOGICAL AND PHYSICAL STRESSORS IMPAIR BLOOD-BRAIN BARRIER FUNCTIONING......Page 147
D. BLOOD-BRAIN BARRIER AS A COMPLEX TRAIT WITH GENETIC AND PHYSIOLOGICAL COMPONENTS: PROSPECTS......Page 148
VI. SUMMARY......Page 149
REFERENCES......Page 150
CONTENTS......Page 157
I. INTRODUCTION......Page 158
A. GENERAL ASPECTS......Page 159
B. ABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION......Page 160
C. PHARMACOKINETICS OF PYRIDOSTIGMINE......Page 165
D. PHARMACODYNAMICS OF PYRIDOSTIGMINE BROMIDE: USE AS A PRETREATMENT DRUG......Page 166
1. Stress......Page 172
3. Gender and Age......Page 177
B. PHARMACOKINETICS OF PHYSOSTIGMINE......Page 178
C. PHARMACODYNAMICS OF PHYSOSTIGMINE......Page 182
D. INFLUENCE OF PHYSICAL STRESS ON PHARMACOKINETICS AND PHARMACODYNAMICS......Page 185
E. EFFECT OF SOMAN ON PHARMACOKINETICS AND PHARMACODYNAMICS......Page 188
IV. NEOSTIGMINE......Page 189
V. SUMMARY......Page 192
REFERENCES......Page 193
I. INTRODUCTION......Page 202
III. SCAVENGER PROTECTION IN RODENTS......Page 204
IV. PROPHYLAXIS AGAINST SOMAN INHALATION TOXICITY IN GUINEA PIGS WITH HUMAN BUTYRYLCHOLINESTERASE (HuBChE)......Page 206
VI. EXPERIMENTS WITH NON-HUMAN PRIMATES......Page 207
VII. IMPROVING THE BIOSCAVENGING CAPABILITY OF ChE......Page 213
B. SITE-SPECIFIC MUTAGENESIS OF AChE......Page 214
C. OP HYDROLYZING ENZYMES, E.G., OPH, OPAA, PARAOXONASE, PARATHION HYDROLASE, ETC.......Page 216
D. CARBOXYLESTERASE AS A BIOSCAVENGER......Page 217
F. IMMOBILIZED CHE FOR THE DECONTAMINATION OF OP......Page 219
REFERENCES......Page 221
I. INTRODUCTION......Page 226
II. CURRENT THERAPY FOR NERVE AGENT EXPOSURE......Page 228
III. NERVE AGENT BIOSCAVENGERS: AN ALTERNATIVE TO CONVENTIONAL APPROACHES......Page 229
B. ENZYMES......Page 231
V. CATALYTIC BIOSCAVENGERS......Page 239
VII. BEHAVIORAL EFFECTS OF SCAVENGERS ALONE......Page 244
VIII. SUMMARY......Page 246
REFERENCES......Page 248
I. INTRODUCTION......Page 255
II. CLINICAL EFFECTS OF SULFUR MUSTARD......Page 256
A. CARCINOGENESIS......Page 257
D. SCARRING, PIGMENTATION CHANGES, AND CANCER OF EPITHELIAL SURFACES......Page 258
F. SUMMARY FOR SYMPTOMATIC EXPOSURES......Page 259
A. CARCINOGENESIS......Page 261
B. RADIATION......Page 262
IV. IN VITRO STUDIES OF SULFUR MUSTARD TOXICITY......Page 263
V. DOSE DEPENDENCY OF THE MUSTARD LESION......Page 264
REFERENCES......Page 265
CONTENTS......Page 271
I. INTRODUCTION......Page 272
II. THE POPULATION AT RISK......Page 275
III. OUTCOMES IN THE POPULATION AT RISK......Page 276
A. MORTALITY......Page 277
B. MORBIDITY......Page 279
C. SYMPTOM PREVALENCE......Page 280
D. REPRODUCTIVE OUTCOMES......Page 281
IV. SUBSETS OF THE POPULATION AT RISK: SYMPTOM-BASED CLUSTERS......Page 282
A. 123RD ARCOM......Page 283
C. SEABEES......Page 284
D. REPRODUCTIVE EFFECTS......Page 285
A. INFECTIOUS DISEASES......Page 286
B. IMMUNIZATIONS, PESTICIDES, AND OCCUPATIONAL EXPOSURES......Page 287
C. DEPLETED URANIUM......Page 288
E. CHEMICAL AND BIOLOGICALWARFARE AGENTS......Page 289
F. KHAMISIYAH, IRAQ......Page 290
VI. SUBSETS ENROLLED IN REGISTRIES......Page 293
VII. OUTCOMES IN SUBPOPULATIONS IN REGISTRIES......Page 295
VIII. IS THERE A SINGLE PGW SYNDROME? THE PROBLEM WITH CASE DEFINITION......Page 299
IX. FUTURE RESEARCH DIRECTIONS......Page 300
X. ASSOCIATION VS. CAUSATION IN ENVIRONMENTAL EPIDEMIOLOGY......Page 301
ACKNOWLEDGMENTS......Page 305
REFERENCES......Page 306
I. INTRODUCTION......Page 310
II. CYANIDE EXPOSURE......Page 311
III. SYMPTOMS PRODUCED BY CYANIDE......Page 312
IV. CHEMICAL REACTIVITY OF CYANIDE......Page 314
V. METABOLISM OF CYANIDE......Page 315
C. OXIDATIVE STRESS IN NEURONAL CELLS AND CYANIDE......Page 317
D. HYPERPOLARIZATION BY CYANIDE......Page 318
VII. EFFECTS OF CYANIDE ON THE HEART......Page 319
IX. PRODUCTION OF CYANIDE IN NEURAL TISSUE......Page 321
XI. SUMMARY......Page 322
REFERENCES......Page 323
CONTENTS......Page 329
I. INTRODUCTION......Page 330
II. HISTORICAL PERSPECTIVES......Page 331
A. CHLOROBENZYLIDENE MALONONITRILE (CS)......Page 334
B. DIBENZ (B,F)1:4-OXAZEPINE (CR)......Page 335
IV. CLINICAL ASPECTS OF RIOT-CONTROL AGENTS......Page 336
VI. OCULAR AND CUTANEOUS EFFECTS OF RIOT-CONTROL AGENTS......Page 337
A. O-CHLOROBENZYLIDENE MALONONITRILE) (CS)......Page 340
1. Mammalian Toxicology......Page 341
3. Reproductive and Developmental Effects......Page 343
5. Metabolism, Metabolic Fate, and Mechanisms......Page 344
6. Human Toxicology......Page 346
7. Human Toxicology......Page 354
8. Ocular and Cutaneous Effects (Human)......Page 355
1. Mammalian Toxicology......Page 357
4. Metabolism, Metabolic Fate, and Mechanisms......Page 359
D. OLEORESIN CAPSICUM (OC)......Page 360
1. Mammalian Toxicology......Page 361
2. Ocular and Cutaneous Effects......Page 363
3. Mutagenicity and Carcinogenicity......Page 364
5. Human Toxicology......Page 365
1. Toxicology and Physiological Effects......Page 367
2. Human Toxicology......Page 368
VIII. SUMMARY......Page 369
REFERENCES......Page 370
I. INTRODUCTION......Page 381
B. SYMPTOMOLOGY......Page 383
C. FUNCTIONAL DOMAINS OF BONT......Page 384
A. FOODBORNE BOTULISM......Page 385
C. INFANT BOTULISM......Page 386
III. TREATMENT OPTIONS......Page 387
1. Potassium Channel Blockers......Page 388
a. Inhibitors of binding......Page 390
b. Inhibitors of internalization......Page 391
c. Inhibitors of metalloprotease activity......Page 392
IV. CONCLUSIONS AND FUTURE RESEARCH......Page 394
REFERENCES......Page 395
I. INTRODUCTION......Page 400
II. CHEMICAL WARFARE (CW) AGENTS AND PERFORMANCE......Page 401
III. COUNTERMEASURES AND PERFORMANCE......Page 404
IV. SUMMARY......Page 409
REFERENCES......Page 410
CONTENTS......Page 415
I. INTRODUCTION......Page 416
A. EXECUTIVE INITIATIVES......Page 417
B. LEGISLATIVE INITIATIVES......Page 418
C. THE FEDERAL RESPONSE PLAN......Page 419
A. MEANS OF INTOXICATION......Page 420
2. Vesicants......Page 422
1. Nerve Agents......Page 423
2. Vesicants......Page 424
A. CIVILIAN VS. MILITARY RESPONSE CONSIDERATIONS......Page 425
B. THE ISRAELI MODEL......Page 426
C. CHEMICAL STOCKPILE EMERGENCY PREPAREDNESS PROGRAM......Page 427
B. HAZMAT RESPONSE......Page 428
C. CURRENTLY AVAILABLE DETECTION TECHNOLOGY......Page 429
D. LABORATORY ANALYSIS......Page 430
1. Nerve Agents......Page 431
1. Training......Page 432
4. Applied Research......Page 433
5. Mass Casualty Decontamination......Page 434
VI. ISSUES RELATED TO LOW-DOSE EXPOSURE TO CHEMICAL AGENTS......Page 436
REFERENCES......Page 437