Yoshida / Hagihara / Ebashi Toxicology and Experimental Models

Proceedings of the 8th International Congress of Pharmacology, Tokyo, 1981
1. Auflage 2013
ISBN: 978-1-4831-4848-9
Verlag: Elsevier Science & Techn.
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 366 Seiten, Web PDF

Advances in Pharmacology and Therapeutics II, Volume 5: Toxicology and Experimental Models is the fifth of a six-volume compilation of the scientific papers of invited speakers of the Eighth International Congress of Pharmacology. Organized into six parts, this book begins by elucidating the rational interpretation of species and strain differences in toxicity for the prediction of risk to man. Subsequent parts discuss the chemical interactions resulting in liver and kidney injury; the role of heme synthesis and degradation in predicting drug toxicity; and delayed toxic effects of pre- and perinatal drug exposure. Other chapters describe models of experimental peptic ulcers and therapeutic agents and models and quality control of laboratory animals.

Autoren/Hrsg.

Yoshida, H.

Hagihara, Y.

Ebashi, S.

Inhaltsverzeichnis

1;Front Cover;1
2;Toxicology and Experimental Models;4
3;Copyright Page;5
4;Table of Contents;6
5;Introduction;10
6;Part I: SYMPOSIUM The Rational Interpretation of Species and Strain Differences in Toxicity for the
Prediction of Risk to Man;12
6.1;Chapter 1. The Rational Interpretation of Species and Strain Differences for the Prediction o fRisk to Man
Introduction;14
6.1.1;INTRODUCTION;14
6.1.2;REFERENCES;17
6.2;Chapter 2. The Potential Value of Immunopathology
in Toxicity Studies;18
6.2.1;ABSTRACT;18
6.2.2;KEYWORDS;18
6.2.3;PRESENT POSITION;18
6.2.4;POSSIBLE STRATEGIES;19
6.2.5;TOXICITY STUDIES IN RATS AND DOGS;20
6.2.6;MINIMAL REQUIREMENTS FOR IMMUNO-TOXICOLOGY;26
6.2.7;SPECIFIC IMMUNOPATHOLOGICAL INVESTIGATIONS;26
6.2.8;CONCLUSION;27
6.2.9;REFERENCES;27
6.3;Chapter 3. Lessons from Studies in Animals for the Evaluation of Human Risk from
Teratogenic Agents;28
6.3.1;ABSTRACT;28
6.3.2;KEYWORDS;28
6.3.3;INTRODUCTION;28
6.3.4;EMBRYONIC NUTRITION;30
6.3.5;IN VITRO TERATOGENESIS;36
6.3.6;CONCLUSION;37
6.3.7;REFERENCES;37
6.3.8;ACKNOWLEDGEMENTS;39
6.4;Chapter 4. Genetic Variability in Man as a Complicating Factor in the Extrapolation
of Toxicological Data from Animals;40
6.4.1;ABSTRACT;40
6.4.2;KEYWORDS;40
6.4.3;INTRODUCTION;40
6.4.4;INTER-SUBJECT VARIABILITY IN DRUG METABOLISM;41
6.4.5;PHARMACOGENETICS - RECENT FINDINGS;42
6.4.6;IN VITRO STUDIES OF HUMAN DRUG METABOLISM;45
6.4.7;ACKNOWLEDGEMENTS;48
6.4.8;REFERENCES;48
6.5;Chapter 5. The Rational Interpretation of Species and Strain Differences in Toxicity for the Prediction of Risk to Man: Review and
Concluding Remarks;52
6.5.1;ABSTRACT;52
6.5.2;KEYWORDS;52
6.5.3;REFERENCES;60
7;Part II: SYMPOSIUM Chemical Interactions Resulting in Liver
and Kidney Injury;64
7.1;Chapter 6. Ethanol Potentiation of Liver Injury;66
7.1.1;ABSTRACT;66
7.1.2;KEYWORDS;66
7.1.3;INTRODUCTION;66
7.1.4;MECHANISM(S) OF ACTION;68
7.1.5;CLINICAL IMPLICATIONS;72
7.1.6;ACKNOWLEDGEMENTS;73
7.1.7;REFERENCES;73
7.2;Chapter 7. Potentiation of Liver and Kidney Injury
by Ketones and Ketogenic Substances;76
7.2.1;ABSTRACT;76
7.2.2;KEYWORDS;76
7.2.3;INTRODUCTION;76
7.2.4;DOSE-RESPONSE CONSIDERATIONS;77
7.2.5;TIME INTERVAL AND POTENTIATION;80
7.2.6;CHAIN-LENGTH AND POTENTIATION;80
7.2.7;HEPATOTOXICITY INDUCED BY OTHER HALOALKANES;80
7.2.8;POTENTIATION OF CHOLESTATIC REACTIONS;82
7.2.9;POTENTIATION OF NEPHROTOXICITY;82
7.2.10;MECHANISMS INVOLVED;83
7.2.11;ACKNOWLEDGEMENT;84
7.2.12;REFERENCES;84
7.3;Chapter 8. Biochemical Mechanisms of Acetaminophen (Paracetamol) Induced
Hepatic and Renal Toxicity;88
7.3.1;ABSTRACT;88
7.3.2;KEY WORDS;88
7.3.3;FACTORS INTERACTING TO ENHANCE OR DECREASE ACUTE ACETAMINOPHEN
TOXICITY.;89
7.3.4;FACTORS INTERACTING TO ENHANCE OR
DECREASE CHRONIC ACETAMINOPHEN TOXICITY;91
7.3.5;REFERENCES;95
7.4;Chapter 9. The Hepatotoxicity and Nephrotoxicity of
Hexachlorobutadiene;98
7.4.1;ABSTRACT;98
7.4.2;KEYWORDS;98
7.4.3;INTRODUCTION;98
7.4.4;RESULTS AND DISCUSSION;99
7.4.5;Acknowledgements;106
7.4.6;References;106
7.5;Chapter 10. Modulation of Nephrotoxicity by
Environmental Chemicals;108
7.5.1;ABSTRACT;108
7.5.2;KEY WORDS;108
7.5.3;INTRODUCTION;108
7.5.4;ENVIRONMENTAL CONTAMINANTS;109
7.5.5;SUMMARY;113
7.5.6;ACKNOWLEDGEMENTS;113
7.5.7;REFERENCES;113
8;Part III: SYMPOSIUM Heme Synthesis and Degradation:
Its Role in Predicting Drug Toxicity;116
8.1;Chapter 11. Heme Synthesis and Degradation: Its Role in Predicting Drug Toxicity —
Opening Remarks;118
8.1.1;INTRODUCTORY REMARKS;118
8.1.2;REFERENCES;121
8.2;Chapter 12. Effect of Drugs and Chemicals on d-Aminolevulinic Acid Synthase, the Ratelimiting
Enzyme of Heme Synthesis;122
8.2.1;ABSTRACT;122
8.2.2;KEYWORDS;122
8.2.3;INTRODUCTION;123
8.2.4;REGULATION OF ALA SYNTHASE ACTIVITY;124
8.2.5;MECHANISMS BY WHICH DRUGS AND CHEMICALS
INDUCE ALA SYNTHASE;125
8.2.6;INDUCTION OF HEPATIC ALA SYNTHASE
BY DRUGS IN HUMAN HEPATIC PORPHYRIA;128
8.2.7;ACKNOWLEDGMENT;129
8.2.8;REFERENCES;129
8.3;Chapter 13. Effects of Drugs and Metals on Heme
Degradation by the Heme Oxygenase System;132
8.3.1;ABSTRACT;132
8.3.2;KEYWORDS;132
8.3.3;INTRODUCTION;132
8.3.4;EXPERIMENTAL OBSERVATIONS;134
8.3.5;COMMENTS;139
8.3.6;ACKNOWLEDGMENT;140
8.3.7;REFERENCES;140
8.4;Chapter 14. Liver Haem as a Target for Drug Toxicity;142
8.4.1;ABSTRACT;142
8.4.2;KEYWORDS;142
8.4.3;INTRODUCTION;142
8.4.4;EFFECT OF UNSATURATED DRUGS ON LIVER CYTOCHROME P-450;143
8.4.5;LIVER ACCUMULATION OF N-METHYL PROTOPORPHYRIN AFTER
DDC AND GRISEOFULVIN;144
8.4.6;MECHANISM OF PRODUCTION OF N-METHYL PROTOPORPHYRIN BY DDC;146
8.4.7;REFERENCES;148
8.5;Chapter 15. Toxic Effects of Metals on the Synthesis
and Disposition of Heme;150
8.5.1;ABSTRACT;150
8.5.2;KEY WORDS;150
8.5.3;INTRODUCTION;150
8.5.4;THE EFFECT OF METALS ON HEME BIOSYNTHESIS;151
8.5.5;THE EFFECT OF FASTING ON CARDIAC ALA SYNTHETASE
ACTIVITY AND HEME BIOSYNTHESIS IN THE HEART;154
8.5.6;EFFECT OF COBALT ON ALA SYNTHETASE ACTIVITY IN FRIEND ERYTHROLEUKEMIC CELLS;155
8.5.7;ACKNOWLEDGMENT;156
8.5.8;REFERENCES;156
8.6;Chapter 16. The Heme Biosynthetic Pathway in the Prediction of Haloaromatic Hydrocarbon
Toxicity;158
8.6.1;ABSTRACT;158
8.6.2;KEYWORDS;158
8.6.3;INTRODUCTION;158
8.6.4;THE TURKISH EPIDEMIC AND HEXACHLOROBENZENE PORPHYRIA;160
8.6.5;PORPHYRIA DUE TO TCDD;161
8.6.6;STUDIES ON THE MECHANISMS OF PORPHYRIA DUE TO TCDD;162
8.6.7;STUDIES OF PORPHYRIN METABOLISM: PREDICTION OF HEPATOTOXICITY;165
8.6.8;POPULATION SCREENING;166
8.6.9;ACKNOWLEDGEMENT;167
8.6.10;REFERENCES;167
9;Part IV: SYMPOSIUM Delayed Toxic Effects of Pre- and Perinatal
Drug Exposure;172
9.1;Chapter 17. An Overview on Delayed Toxic Effects of
Pre- and Perinatal Drug Exposure;174
9.1.1;ABSTRACT;174
9.1.2;KEYWORDS;174
9.1.3;INTRODUCTION;174
9.1.4;REFERENCES;185
9.2;Chapter 18. Improvements in the Postnatal Detection
of Central Nervous System Defects;188
9.2.1;1 · Prenatal
physiology;189
9.2.2;2.The newborn Period;190
9.2.3;3 · Methodology;190
9.2.4;4. Results;191
9.2.5;SUMARY AND CONCLUSIONS;203
9.2.6;BIBLIOGRAPHIE;205
9.3;Chapter 19. Maldevelopment of CNS Induced by Perinatal Metabolic Insults and Possibilities of Its
Regulation;210
9.3.1;ABSTRACT;210
9.3.2;KEYWORDS;210
9.3.3;INTRODUCTION;210
9.3.4;BEHAVIORAL TERATOLOGY MODELS;213
9.3.5;PERINATAL DISTRESS IN HIGH-RISK NEWBORNS;217
9.3.6;CONCLUSION;219
9.3.7;REFERENCES;219
9.4;Chapter 20. Altered Postnatal Development Following Intrauterine Exposure to Hormonally Active Chemicals;222
9.4.1;ABSTRACT;222
9.4.2;KEY WORDS;222
9.4.3;INTRODUCTION;222
9.4.4;TRANSPLACENTAL TOXICOLOGY;223
9.4.5;TRANSPLACENTAL TOXICOLOGY: INFERTILITY IN OFFSPRING;223
9.4.6;TRANSPLACENTAL TOXICOLOGY OF DIETHYLSTILBESTROL (DES);226
9.4.7;ACKNOWLEDGEMENT;229
9.4.8;REFERENCES;229
9.5;Chapter 21. WORKSHOP
Alcohol Intoxication and Withdrawal;232
9.6;Chapter 22. Alcohol Intoxication and Withdrawal:
Introductory Remarks;234
9.6.1;HISTORICAL COMMENTS;234
9.6.2;BACKGROUND ON ALCOHOL RESEARCH;234
9.6.3;ETHANOL METABOLISM;234
9.6.4;METABOLIC CHANGES INDUCED BY ETHANOL: METABOLIC TOLERANCE;235
9.6.5;CELLULAR BASIS OF THE ACTION OF ETHANOL ON THE NERVOUS
SYSTEM: CENTRAL NERVOUS SYSTEM TOLERANCE;236
9.6.6;CONCLUSION;236
9.6.7;REFERENCES;237
9.6.8;KEYWORDS;237
9.7;Chapter 23. The Role of Mitochondrial NADH Reoxidation in the Hepatic Metabolism of Ethanol: Studies with Perfused Livers from Ethanol and CCl4-Treated
Rats;238
9.7.1;ABSTRACT;238
9.7.2;INTRODUCTION;238
9.7.3;MATERIALS AND METHODS;239
9.7.4;RESULTS & DISCUSSION;240
9.7.5;KEY WORDS;242
9.7.6;REFERENCES;242
9.8;Chapter 24. Ethanol and Membrane Cholesterol;244
9.8.1;ABSTRACT;244
9.8.2;KEYWORDS;244
9.8.3;ACKNOWLEDGEMENT;247
9.8.4;REFERENCES;247
9.9;Chapter 25. Susceptibility to Ethanol of Neurons in Lateral Vestibular, Spinal Trigeminal and
Lateral Geniculate Nuclei;250
9.9.1;ABSTRACT;250
9.9.2;KEYWORDS;250
9.9.3;INTRODUCTION;250
9.9.4;METHODS;251
9.9.5;RESULTS;251
9.9.6;DISCUSSION;253
9.9.7;REFERENCES;255
9.10;Chapter 26. Dissociation of Components of Ethanol
Intoxication and Tolerance;256
9.10.1;ABSTRACT;256
9.10.2;KEYWORDS;256
9.10.3;INTRODUCTION;256
9.10.4;PROCEDURES AND RESULTS;257
9.10.5;DISCUSSION;260
9.10.6;ACKNOWLEDGEMENTS;261
9.10.7;REFERENCES;261
10;Part V: WORKSHOP Models of Experimental Peptic Ulcers
and Therapeutic Agents;264
10.1;Chapter 27. Models of Experimental Peptic Ulcers and
Therapeutic Agents;266
10.1.1;KEYWORDS;266
10.2;Chapter 28. Possible Roles of Central Gatecholamines
in Regulation of Gastric Functions;268
10.2.1;ABSTRACT;268
10.2.2;KEY WORDS;268
10.2.3;INTRODUCTION;268
10.2.4;CENTRAL NA ON STRESS-INDUCED GASTRIC ULCER;269
10.2.5;CENTRAL MONOAMINES IN REGULATION OF GASTRIC ACID
SECRETION AND MUCOSAL BLOOD FLOW;269
10.2.6;RELATION OF MUCOSAL BLOOD FLOW TO GASTRIC ACID
SECRETION;271
10.2.7;REFERENCES;271
10.3;Chapter 29. Duodenal Ulcer and Dopamine:
New Elements in Pathogenesis and Therapy;274
10.3.1;ABSTRACT;274
10.3.2;KEYWORDS;274
10.3.3;INTRODUCTION;274
10.3.4;MATERIALS AND METHODS;275
10.3.5;RESULTS AND DISCUSSION;275
10.3.6;ACKNOWLEDGEMENTS;279
10.3.7;REFERENCES;279
10.4;Chapter 30. Defensive Mechanism in Peptic Ulcer and
Assessment of Anti-ulcer Agents;280
10.4.1;ABSTRACT;280
10.4.2;KEYWARDS;280
10.4.3;INTRODUCTION;280
10.4.4;INCREASE IN THE HYDROGEN ION PERMEABILITY OF THE GASTRIC MUCOSA AS
THE RESULT OF CELLULAR DAMAGE;280
10.4.5;INCREASE IN HYDROGEN ION PER- MEABILITY OF GASTRIC MUCOSA IN ASPIRIN-INDUCED ULCERATION IN
RATS;281
10.4.6;CONCLUSIONS;285
10.4.7;REFERENCES;285
10.5;Chapter 31. Differential Role of Histamine in Duodenal
versus Gastric Experimental Ulcer;286
10.5.1;ABSTRACT;286
10.5.2;KEYWORDS;286
10.5.3;INTRODUCTION;286
10.5.4;EXOGENOUS HISTAMINE AND ULCER INDUCTION;287
10.5.5;INDUGENOUS HISTAMINE AND ULCER INDUCTION;287
10.5.6;MECHANISMS OF ACTION OF HISTAMINE IN ULCER PATHOGENESIS;288
10.5.7;ACKNOWLEDGMENT;291
10.5.8;REFERENCES;291
10.6;Chapter 32. Can the Mechanisms of
Aspirin-induced Gastric Mucosal Injury be Identified?;292
10.6.1;ABSTRACT;292
10.6.2;KEYWORDS;292
10.6.3;INTRODUCTION;293
10.6.4;MUCOSAL INJURY INDUCED BY ASPIRIN;293
10.6.5;EFFECT OF ASPIRIN ON MUCOSAL PROSTAGLANDIN FORMATION;293
10.6.6;EFFECT OF ASPIRIN ON GASTRIC MUCOSAL BLOOD FLOW;293
10.6.7;EFFECT OF ASPIRIN ON THE "GASTRIC MUCOSAL BARRIER;294
10.6.8;EFFECT OF ASPIRIN ON GASTRIC ACID SECRETION;294
10.6.9;EFFECT OF ASPIRIN ON GASTRIC MUCUS AND BICARBONATE SECRETION;294
10.6.10;CONCLUSION;295
10.6.11;ACKNOWLEDGEMENT;295
10.6.12;REFERENCES;295
10.7;Chapter 33. Screening of Anti-Ulcer Agents Using
Experimental Ulcer Models;298
10.7.1;ABSTRACT;298
10.7.2;KEYWORDS;298
10.7.3;INTRODUCTION;298
10.7.4;SCREENING METHODS;298
10.7.5;EFFECTS OF ANTI-ULCER AGENTS ON EXPERIMENTAL ULCERS;301
10.7.6;PREVENTION OF RECURRENCE;301
10.7.7;ULCER MODELS IN LARGE ANIMALS;302
10.7.8;SUMMARY;303
10.7.9;REFERENCES;303
11;Part VI: SYMPOSIUM Models and Quality Control of Laboratory
Animals;304
11.1;Chapter 34. Introduction to Models and Quality Control of Laboratory Animals;306
11.1.1;REFERENCES;309
11.2;Chapter 35. Consideration of Provision and Characterization of Animal Models;310
11.2.1;ABSTRACT;310
11.2.2;KEYWORDS;310
11.2.3;INTRODUCTION;310
11.2.4;PRINCIPLES OF EXTRAPOLATION;311
11.2.5;DEVELOPMENT OF NEW ANIMAL MODELS;314
11.2.6;CONCLUSION;317
11.2.7;ACKNOWLEDGEMENT;318
11.2.8;REFERENCES;318
11.3;Chapter 36.
New Animal Models in Pharmaceutical Research;320
11.3.1;ABSTRACT;320
11.3.2;KEYWORDS;320
11.3.3;INTRODUCTION;320
11.3.4;REFERENCES;329
11.4;Chapter 37. Species Variation in Evaluation of Safety of Drugs in the Developing Animal;330
11.4.1;ABSTRACT;330
11.4.2;KEYWORDS;330
11.4.3;INTRODUCTION;330
11.4.4;MOTHER;331
11.4.5;PLACENTA;332
11.4.6;EMBRYO;333
11.4.7;REFERENCES;333
11.5;Chapter 38. Defined Laboratory Animals;336
11.5.1;ABSTRACT;336
11.5.2;KEYWORDS;336
11.5.3;INTRODUCTION;336
11.5.4;CLASSIFICATION OF EXPERIMENTAL ANIMALS;337
11.5.5;SITE OF THE RESPONSE TO THE EXPERIMENT-
DETERMINATION OF THE DRAMATYPE;338
11.5.6;CONTROL AND TESTING OF LABORATORY ANIMALS AND DEFINITION
OF DEFINED LABORATORY ANIMALS;339
11.5.7;GENETICAL AND MICROBIOLOGICAL MONITORING AS A PERFORMANCE
TEST TO OBTAIN DEFINED LABORATORY ANIMALS;340
11.5.8;CONCLUSION;343
11.5.9;REFERENCES;343
11.6;Chapter 39. Quality Control in Diets — the Attainable;346
11.6.1;ABSTRACT;346
11.6.2;KEYWORDS;346
11.6.3;INTRODUCTION;346
11.6.4;DIET MANUFACTURE;347
11.6.5;DIET INGREDIENTS;348
11.6.6;CONTAMINATION IN DIETS;351
11.6.7;MICROBIOLOGICAL CONTROL AND DIET STABILITY;353
11.6.8;COST;355
11.6.9;NUTRIENT VARIATIONS IN FIXED FORMULA DIETS;357
11.6.10;CONCLUSION;357
11.7;Chapter 40. Problems and Improvements
in the Development of Good Laboratory Practice;358
11.7.1;ABSTRACT;358
11.7.2;KEYWORDS;358
11.7.3;INTRODUCTION;358
11.7.4;PROGRAM MILESTONES;359
11.7.5;SCIENCE AND PROCESS;360
11.7.6;GLP CONCEPTS;360
11.7.7;THE PRINCIPAL GLP PROVISIONS;361
11.7.8;FDA"S LABORATORY INSPECTION PROGRAM;362
11.7.9;SUMMARY;363
11.7.10;REFERENCES;363
12;Index;364