Animal Hematotoxicology: A Practical Guide for Toxicologists and Biomedical Researchers

by Evans; G.O.

• ISBN13: 9781420080094
• ISBN10: 1420080091
• Edition: 1st
• Format: Hardcover
• Copyright: 2008-07-25
• Publisher: CRC Press

Summary

Hematology data from in vivotoxicology studies remains one of  the most predictive measures for human risk, as the same measurements made in pre-clinical toxicology studies can be made in early clinical trials.Covering the three main blood cell types ' erythrocytes, leukocytes and thrombocytes, this work is designed to clarify topics for new entrants to the fields of laboratory animal hematology and toxicology, especially those topics where the rules for human hematology do not always apply. An entire chapter is devoted to immunotoxicology, a scientific discipline that is closely aligned with hematology.The text also addresses pre-analytical and analytical variables that affect animal studies, as these play a far more important part when interpreting data in contrast to humans where many of these variables can be well controlled or have less physiological effect. Information has been collated from published papers, textbooks and unpublished data: Readers are provided withkey references to encourage further study

Table of Contents

Preface	p. xi
The Author	p. xiii
Introduction	p. 1
Developing Areas of Interest	p. 5
References	p. 7
Hemopoiesis, Blood Cell Types, and Bone Marrow Examination	p. 9
Hemopoiesis	p. 9
Bone Marrow Stroma	p. 11
Erythrocytes	p. 12
Leukocytes	p. 13
Lymphocytes	p. 14
Platelets	p. 15
Plasma	p. 16
Monocyte-Macrophage System (or Reticuloendothelial System)	p. 16
Bone Marrow Examinations	p. 17
Bone Marrow Smear Preparation	p. 17
Flow Cytometric Examination of Bone Marrow Aspirates	p. 18
In Vitro Techniques	p. 18
Toxic Effects	p. 19
References	p. 20
Erythrocytes, Anemias, and Polycythemias	p. 23
Erythrocyte Morphology Terminology	p. 24
Erythrokinetics	p. 26
Species Characteristics	p. 27
Mouse	p. 27
Rat	p. 28
Beagle Dog	p. 28
Rabbit	p. 28
Hamster	p. 28
Guinea Pig	p. 28
Ferret	p. 28
Nonhuman Primates	p. 28
Marmosets	p. 28
Cat	p. 28
Erythrocytic Functions	p. 29
Derivatives of Hemoglobin	p. 29
Anemia	p. 30
Pseudoanemia	p. 37
Response to and Recovery from Anemia	p. 37
Secondary Anemia	p. 37
Polycythemia	p. 38
General Comments	p. 38
References	p. 39
Additional Erythrocytic Measurements	p. 43
Osmotic Fragility	p. 43
In Vitro Hemolysis	p. 44
Plasma Hemoglobin	p. 45
Plasma Haptoglobin	p. 45
Hematuria	p. 45
Fecal Occult Blood	p. 46
Erythrocyte Sedimentation Rate (ESR)	p. 46
Antiglobulin or Coombs Test	p. 46
Plasma Lactate Dehydrogenase	p. 47
Glutathione	p. 47
Erythropoietin (EPO)	p. 47
Oxygen Dissociation Curves	p. 47
Porphyrins	p. 48
Hemorrheology	p. 49
Glycated Hemoglobin	p. 49
Micronucleus Tests	p. 49
References	p. 50
Iron, Associated Proteins, and Vitamins	p. 55
Iron Metabolism	p. 55
Transferrin	p. 56
Ferritin	p. 57
Cobalamin (Vitamin B[subscript 12])	p. 57
Folate	p. 57
Analytical Methods	p. 58
Iron	p. 58
Transferrin and Ferritin	p. 58
Total Iron-Binding Capacity (TIBC)	p. 59
Unsaturated Iron-Binding Capacity (UIBC)	p. 59
Analyses of Cobalamin and Folate	p. 59
Potential Markers	p. 59
Soluble Transferrin Receptor (sTfR)	p. 59
Additional Reticulocyte Indices	p. 60
Toxic Effects	p. 60
Iron	p. 60
Cobalamin and Folate	p. 61
References	p. 61
Leukocytes	p. 65
Abbreviations	p. 65
LUCs	p. 65
Granulocytes	p. 65
Leukocyte Morphology Terminology	p. 66
Leukocyte Kinetics	p. 67
Species Characteristics	p. 68
Dog	p. 69
Rabbit	p. 69
Guinea Pig	p. 71
Hamster	p. 71
Nonhuman Primates	p. 72
Mouse	p. 72
Rat	p. 72
Functions of Leukocytes	p. 72
Neutrophils	p. 74
Lymphocytes	p. 75
Toxic Effects on Leukocytes	p. 76
Neutrophils	p. 76
Lymphocytes	p. 78
Monocytes	p. 78
Basophils	p. 79
Eosinophils	p. 79
Neoplasias	p. 79
Leukemias	p. 80
Myelodysplasia (MDS)	p. 81
Other Tests Applied to Leukocytes	p. 82
Leukocyte Alkaline Phosphatase	p. 82
Myeloperoxidase	p. 82
Phospholipidosis	p. 82
References	p. 82
Immunotoxicology	p. 85
Components of the Immune System	p. 85
T and B Lymphocytes	p. 85
Other Cells	p. 87
Soluble Mediators	p. 87
Immune Responses	p. 90
Hypersensitivity and Allergy	p. 90
Autoimmunity	p. 91
Assays	p. 91
Flow Cytometry and Antibodies	p. 92
Antibodies	p. 92
T and B Lymphocytes	p. 92
T-Cell-Dependent Antibody Response (TDAR) Assays	p. 93
Sheep Red Blood Cell (SRBC) Assay	p. 93
Keyhole Limpet Hemocyanin (KLH) and Tetanus Toxoid (TT) Assays	p. 93
NK Cells	p. 93
NK Cell Cytotoxic Function	p. 94
Phagocytic Activity and Oxidative Burst Activity of Monocytes and Granulocytes	p. 94
Plasma Globulins	p. 94
Immunoglobulin Measurements	p. 94
Direct Immunoglobulin and Antibodies for Erythrocytes, Neutrophils, and Platelets	p. 95
Complement System	p. 95
Cytokines	p. 95
Host Resistance and Hypersensitivity Studies	p. 95
Immunotoxicity	p. 95
Strategies for Immunotoxicity Testing	p. 97
References	p. 99
Hemostasis	p. 107
Analytical Methods	p. 111
Platelets	p. 111
Mean Platelet Volume	p. 112
Coagulation Cascade	p. 113
Prothrombin Time (PT)	p. 113
Activated Partial Thromboplastin Time (APTT)	p. 114
Bleeding Time (BT)	p. 114
Whole Blood Clotting Time (WBCT)	p. 114
Activated Clotting Time (ACT)	p. 114
Thrombin Time (TT)	p. 114
Fibrinogen	p. 115
Platelet Function Tests	p. 115
Other Factor Assays	p. 116
Toxic Effects on Platelets and Coagulation	p. 117
Effects on the Coagulation Pathways	p. 119
Other Coagulation Factor Measurements	p. 120
References	p. 120
Preanalytical Variables	p. 125
Animals: Species, Strain, Age, and Gender	p. 125
Strain Difference	p. 125
Age-Related Changes	p. 126
Gender	p. 126
Blood Collection	p. 127
Volume and Frequency	p. 127
Anticoagulants	p. 127
Sample Storage	p. 128
Blood Collection Procedures	p. 128
Stress, Environment, and Transportation	p. 130
Nutrition and Fluid Balance	p. 131
Chronobiological Effects	p. 131
Summary	p. 132
References	p. 132
Analytical Variables and Biosafety	p. 139
Blood Films (Smears)	p. 142
Heinz Bodies	p. 143
Reticulocytes	p. 143
Methemoglobin and Sulfhemoglobin Measurements	p. 143
Coagulation	p. 144
Platelet Aggregation Studies	p. 144
Chromogenic Factor Assays	p. 144
General Method Principles	p. 144
Linearity	p. 145
Calibration and Quality Control Materials	p. 146
ELISA Methods	p. 147
Maintenance	p. 147
Biohazards and Chemical Safety	p. 147
References	p. 148
Data Processing and Interpretation	p. 153
Data Definitions and Security	p. 153
Repeated Analyses on the Same Sample	p. 154
Intra- and Inter-Individual Variations	p. 154
Critical Differences	p. 155
Reference Values	p. 156
Data Distributions	p. 156
Statistical Methods	p. 157
Control Groups	p. 158
Statistical Analyses	p. 159
Sensitivity and Specificity	p. 161
Extrapolation of Animal Data to Humans	p. 162
References	p. 163
References for Laboratory Animal Hematology Data	p. 167
SI Units and Conversions	p. 173
Expectable Ranges	p. 175
General Abbreviations	p. 187
Some Common Biochemical Abbreviations	p. 191
	p. 193
Compounds Causing Reductions and Destruction of Erythrocytes	p. 193
Compounds Causing Reductions of Neutrophil Numbers	p. 195
Compounds Affecting Numbers, Function, and Aggregation of Platelets	p. 196
Leukocyte-Cluster of Differentiation	p. 197
Index	p. 201
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