Biomarkers in Toxicology

Description

Cover......Page 1 Biomarkers in Toxicology......Page 2 64. Percellome Toxicogenomics Project as a Source of Biomarkers of Chemical Toxicity......Page 3 Dedication......Page 4 Foreword......Page 5 Part I: Toxicity Testing Models and Biomarkers ......Page 11 49. Biomarkers of Alzheimer's Disease......Page 844 References......Page 13 Transcriptomics......Page 1075 Introduction......Page 854 Characteristics......Page 15 Strain Differences......Page 17 Study Designs......Page 18 Dietary Versus Gavage Methods......Page 20 Dietary Method......Page 22 Technique......Page 24 Intravenous Route......Page 25 Jugular Vein......Page 26 Infusion......Page 27 Intramuscular Route......Page 28 Rectal Route......Page 29 Observations and Physical Examinations......Page 30 Functional Observational Battery......Page 31 Cardiovascular Parameters......Page 32 Position......Page 33 Heart Rate......Page 34 Direct Measurement......Page 35 Tail Clip......Page 36 Jugular Vein......Page 37 Jugular Vein......Page 38 Summary......Page 39 Use in Toxicological Research......Page 40 Species Differences......Page 41 Strain Differences......Page 42 Study Designs......Page 43 Acute Toxicity Studies......Page 44 Chronic Toxicity Studies (26weeks–2years)......Page 45 Carcinogenicity Studies (18–24months)......Page 46 Teratology Studies......Page 47 Genetic Toxicity Studies......Page 48 Microbial Host-Mediated Assay......Page 49 Mouse Ear Swelling Test......Page 50 Dermal Carcinogenicity (Skin Painting) Study......Page 51 Description of Technique......Page 52 Description of Technique......Page 53 Intravenous Injection......Page 54 Description of Technique......Page 55 Description of Technique......Page 56 Description of Technique......Page 57 Description of Technique......Page 58 Inhalation......Page 59 Clinical Observations and Physical Examinations......Page 60 Clinical Laboratory Evaluations......Page 61 Species......Page 62 Chinese Hamster......Page 63 South African Hamster......Page 64 Intraperitoneal Administration......Page 65 Body Weights and Weight Gains......Page 66 Heart Rate......Page 67 Clinical Laboratory......Page 68 Reproductive Hormones......Page 69 Urine Values......Page 70 Strain-Related Considerations......Page 71 Inhalation and Intratracheal Studies......Page 72 Toxicology Studies......Page 73 Cardiomyopathy......Page 74 Osteoarthritis and Degenerative Joint Disease......Page 75 References......Page 76 60. Citrulline: Pharmacological Perspectives and Role as a Biomarker in Diseases and Toxicities......Page 81 Introduction......Page 666 Requirements Expected in a Biomarker for Toxicology Testing and Biomonitoring Xenobiotics Exposure......Page 1114 36. Mycotoxins......Page 401 Intermediate Filaments......Page 993 Concluding Remarks and Future Directions......Page 84 Oral Biomarkers of Exposure and Effects of Select Drugs/Toxicants......Page 926 Safety Pharmacology......Page 89 Importance of Understanding Specific Mechanisms of Toxicity in Drug Development......Page 648 References......Page 92 Structure and Function of Brain Barriers......Page 869 Introduction......Page 440 Potential Chemical Mixtures......Page 96 Personal Experience......Page 734 Comprehensive Selection of Responding mRNAs......Page 1089 Chromosomal Aberrations and Sister Chromatid Exchanges......Page 759 Biomarkers of Hematotoxicity......Page 266 References......Page 287 Prevention and Management of Poisoning......Page 103 Biomarker Validation......Page 635 Gastrointestinal and Hepatic......Page 104 Cell Counts......Page 105 Nephropathies......Page 378 Clinical Pathology......Page 450 Selecting Sample Sources for the Measurement of Biomarkers......Page 107 Concluding Remarks and Future Directions......Page 790 Clinical Chemistry......Page 1003 Multiplexed High Content Solid Phase Immunoassays......Page 540 References......Page 548 References......Page 115 Index......Page 118 Adducts: A Relevant Case of Biomarkers of Exposure......Page 592 Anatomic Structure of the Human Auditory System......Page 120 Gastrins......Page 275 Concluding Remarks and Future Directions......Page 122 Transcriptomics in Biomarker Discovery......Page 1077 Fos B Transcription Factor Is Responsible for the Synaptic Modification Following Meth Abuse......Page 124 Biochemical Aspects......Page 557 Acknowledgments......Page 128 56. Biomarkers of Blood–Brain Barrier Dysfunction......Page 273 Introduction......Page 131 Adverse Outcome Pathways: Principles of Development and Assessment......Page 133 Introduction......Page 774 Prediction of Developmental, Reproductive, and Behavioral Toxicity Using Drosophila melanogaster......Page 135 Toxicomics Profiling Using Drosophila......Page 136 T Cell Lymphocytes......Page 403 Risk Factors......Page 805 Mitochondrial Toxicity......Page 186 Oral Physiology and Pharmacodynamics......Page 139 Introduction......Page 987 INTRODUCTION......Page 145 REASONS FOR DEVELOPING ALTERNATIVES TO ANIMAL TESTS AND BIOMARKERS......Page 146 References......Page 147 Biomarkers of Effect for Toxicology Testing......Page 149 Cadmium......Page 691 Bacterial Mutation Assay (Ames Assay)......Page 151 Erythrocytes......Page 391 Citrulline and Cardiovascular Effects......Page 152 Unique Zebrafish Model......Page 153 Genetic Biomarkers of Petroleum Exposure......Page 545 Isolated Tissues......Page 154 Receptor Binding Studies......Page 155 Biomarkers of Anabolic Agents......Page 156 Glutathione S-transferase P1......Page 158 Autoantibodies as Biomarkers for Peripheral Nervous System Disorders......Page 200 References......Page 161 Introduction......Page 164 Biomarkers of Exposure for Monitoring Xenobiotics Exposure......Page 795 Biomarker of Drug-Induced Kidney Toxicity......Page 169 Concluding Remarks and Future Directions......Page 875 References......Page 575 54. Oral Pathology Biomarkers......Page 172 Introduction......Page 726 Epidemiology......Page 579 Cyclopia......Page 421 Sample Preparation......Page 175 Diagnostic Biomarkers......Page 176 Ergotism......Page 207 Biomarkers of Exposure......Page 177 Infectious Agents and Sepsis......Page 1079 Sampling Sputum, Nasal Lavage, and Exhaled Breath......Page 179 Methylmercury......Page 180 References......Page 181 Biomarkers of Susceptibility......Page 243 46. Risk Factors as Biomarkers of Susceptibility in Breast Cancer......Page 185 Biomarkers......Page 920 Reactivity of Lipid Peroxidation Products......Page 187 Tetracycline/Minocycline......Page 757 Ovarian Cancer......Page 821 Merging the TGP Data to Percellome Database......Page 534 Antiinflammatory Drugs......Page 188 Placental DNA Adducts as Biomarkers......Page 189 Effects of Organic Solvents and Polybrominated Diphenyl Ethers on Intermediate Filaments......Page 826 Endocrine Alopecia......Page 906 Biomarkers of Traumatic Brain Injury Affecting Peripheral Nervous System......Page 190 Epigenomic......Page 393 Opioids......Page 873 Opioid Actions Are Orchestrated Through Inhibitory G Protein (Gi/Go)......Page 191 Biomarker of Effects......Page 192 Potential Biomarkers of Sleeping Disorders (Apnea, Insomnia, and Desynchronosis)......Page 194 MicroRNAs as Potential Biomarkers of Peripheral Nervous System Injury......Page 195 Pharmacogenomic Biomarkers for Preventing Chemical-Induced Peripheral Neuropathy......Page 196 Biomarkers From Studies on Inherited Peripheral Neuropathies......Page 197 Biomarkers of Demyelination Injuries......Page 198 Biomarkers of Organophosphorus-Ester Induced Delayed Neurotoxicity......Page 199 Role of Peripheral Nervous System in Parkinson's Disease and Lewy Body Disease......Page 201 Emerging Avenues of Peripheral Nervous System Biomarker Developments: Exosomes......Page 202 References......Page 203 Introduction......Page 206 Copper and Iron......Page 955 Vascular System......Page 208 BIOMARKERS AND BIOMONITORING OF EXPOSURE......Page 382 Concluding Remarks and Future Directions......Page 209 Ivermectin and Selamectin......Page 210 Alopecia and Inhibition of Hair Growth (Mimosine Toxicity)......Page 211 PYRROLIZIDINE ALKALOID-CONTAINING PLANTS......Page 620 Metabolomics Biomarkers in Neurotoxicity......Page 1069 Biomarkers of Susceptibility......Page 212 Toxicology......Page 616 Endogenous Cannabinoid Ligand Interaction With Cannabinoid Type 1 Receptor Regulates Expression of Genes Involved in Long-T .........Page 838 Placental Growth Factor......Page 213 Cardiac Biomarkers of Illegal Drugs, Chemicals, and Terror Agents......Page 214 Illegal Drugs......Page 215 Future Trends in Cardiovascular Biomarkers......Page 217 MicroRNAs as Cardiac Biomarkers......Page 218 Risk Prediction of Cardiovascular Events......Page 220 References......Page 221 35. Freshwater Cyanotoxins......Page 578 Introduction......Page 226 Overview of Regulation of Dietary Supplements in the United States......Page 668 Concluding Remarks and Future Directions......Page 1064 Cocaine......Page 228 Dietary Choices......Page 688 Posttranslational Modifications of Tau Cause Aggregation and Synaptic Starving......Page 846 Herbicides......Page 229 Effects of Heavy Metals on Microfilaments......Page 834 Specific Gene Mutations......Page 423 Other Genotoxic Biomarker Detection Methods......Page 780 Apoptosis Markers......Page 451 Benzo(a)pyrene......Page 1108 Biomarkers in Exhaled Breath Condensate......Page 233 Activities of Lactate Dehydrogenase, γ-Glutamyltransferase, N-Acetylglucosaminidase, and Proteases/Antiproteinases......Page 235 Oxidation By-Products and Antioxidants......Page 236 Cytokines, Chemokines, and Growth Factors......Page 237 Bronchoalveolar Lavage Fluid Cells as a Determinant of Lung Inflammation......Page 238 Surfactant, Other Lung-Specific Proteins, and Immunological Biomarkers......Page 239 Kidney Calcinosis......Page 240 Citrulline as a Biomarker in Citrin Deficiency......Page 1042 miRNA......Page 241 Pyrrolizidine Alkaloids—Symphytum Spp. (Common Name, Comfrey)......Page 242 Snake Toxins......Page 357 Introduction......Page 248 Solvents......Page 249 Radiation-Attributable Disease......Page 485 Dietary Ingredient Safety......Page 250 New Repeated Dosing Study......Page 251 Prevention, Management, and Treatment......Page 252 Metabolomic......Page 253 Review of Emerging Biomarkers......Page 254 BIOMARKERS OF COMFORT, MOBILITY, FUNCTION, AND INFLAMMATION AND PAIN......Page 637 Grating-coupled Surface Plasmon Resonance Microarray Analysis......Page 454 Proteomic Biomarkers of Hepatotoxicity......Page 255 Metabolomics Biomarkers in Hepatotoxicity......Page 258 MicroRNAs as Biomarkers of Hepatotoxicity......Page 259 Concluding Remarks and Future Directions......Page 861 References......Page 827 Mitochondrial Function: General Overview......Page 264 TOXICOKINETICS......Page 462 Proteinuria......Page 265 Genotype–Phenotype Associations......Page 551 Hepatic Biomarkers......Page 1078 Monocytes......Page 392 Matrix Metalloproteinases......Page 268 Concluding Remarks and Future Directions......Page 269 Introduction......Page 375 Pesticides and Herbicides......Page 728 References......Page 274 References......Page 574 Teeth......Page 367 Paraquat......Page 353 Biomarkers......Page 587 α-Synuclein and Abnormal Protein Accumulations......Page 276 Chemical Biomarkers of Ochratoxin A......Page 595 Anatomic Pathology......Page 1004 Female Reproductive Aging......Page 291 MicroRNA......Page 277 Manganese......Page 278 References......Page 279 A......Page 756 Male Reproductive Biomarkers......Page 282 Study Design and Planning......Page 1061 Molecular Biomarkers for In Vitro Testing Toxicity......Page 1119 Biomarkers of Inflammation......Page 891 Female Puberty......Page 289 Tobacco and Risk Continuum......Page 1080 Concluding Remarks and Future Directions......Page 292 48. Prostate Cancer Biomarkers......Page 297 Introduction......Page 542 Screening and Early Detection for Prostate Cancer......Page 298 Other Biomarkers of Exposure......Page 299 Biomarkers and Mechanism of Action......Page 372 Application of Safety Biomarkers in Different Phases of Drug Development......Page 633 Chromium (VI)......Page 307 Biomarkers of Exposure......Page 308 Challenges of the Development of Biomarkers of Exposure to Engineered Nanomaterials Due to Their Biokinetics......Page 312 Biomarkers in the Oral Cavity......Page 924 Epigenetic Changes in Human Placenta as Potential Biomarkers of Toxicity......Page 318 Cholinesterase Inhibition......Page 874 Susceptibility......Page 784 Experimental Methods Concerning Placenta......Page 322 References......Page 323 Biomarkers of Exposure......Page 334 Concluding Remarks and Future Directions......Page 851 Excitotoxicity and Oxidative Damage......Page 972 References......Page 336 References......Page 399 J......Page 337 Nomenclature......Page 455 L......Page 1155 Activation By-Products of Pancreatic Trypsinogen and Carboxypeptidase B......Page 338 N......Page 1158 Cathepsins......Page 339 U......Page 340 Differentially Altered Proteins, Metabolites, Small Molecules, and microRNA......Page 341 Comparison of Biomarkers Between Acute and Chronic Pancreatitis......Page 342 References......Page 343 55. Biomarkers of Mitochondrial Dysfunction and Toxicity......Page 347 Introduction......Page 831 B......Page 845 Cholinergic Effects......Page 348 Excitotoxicity and Oxidative/Nitrosative Stress......Page 349 Creatine Kinase and Creatine Kinase Isoenzymes......Page 350 Lactate Dehydrogenase and Lactate Dehydrogenase Isoenzymes......Page 351 Histopathological Alterations......Page 352 Lipidomics......Page 354 Mitochondrial Dysfunction in Diabetes......Page 356 Effects of Organophosphorus Esters on Intermediate Filaments......Page 871 α-Methylacyl Coenzyme A Racemase......Page 518 Metal Toxicity and Oxidative Injury......Page 976 Biomarkers of Drug-Induced Brain Injury......Page 360 Concluding Remarks and Future Directions......Page 361 66. Biomarkers for Testing Toxicity and Monitoring Exposure to Xenobiotics......Page 366 Introduction......Page 1113 Heavy Metals......Page 1103 Histone Acetylation......Page 505 Molecular Biomarkers in Age-Related Macular Degeneration......Page 369 Molecular Biomarkers in Ocular Oncology......Page 370 Microfilaments......Page 990 Effects of Heavy Metals on Microtubules......Page 377 Puberty......Page 806 Hamsters......Page 379 Prognostic Factors......Page 807 Antimalarial Drugs......Page 380 Industrial Chemicals......Page 381 Detection and Screening......Page 384 Purine Nucleotide Phosphorylase......Page 640 Acoustic Immitance Test......Page 385 Acoustic Brain Stem Response Testing......Page 386 Methyl Parathion......Page 1105 Ovarian Cancer......Page 825 Results and Discussion......Page 1091 Biomarkers and Biomarker Signatures in Disease: a Variety of Marker Classes and Possible Inferences......Page 1048 Assessing Exposures......Page 390 Gene Mutations and Their Mechanism of Action......Page 781 E......Page 394 Toxicology......Page 615 Markers of Bone Marrow Toxicity......Page 397 Sarcosine......Page 837 Progenitor Cell Colony Formation......Page 398 List of Abbreviations......Page 1027 DNA-Methylation and MicroRNAs (miR)......Page 404 Biomarkers Associated with the Presence of Banned Ingredients......Page 405 References......Page 437 Antibody Assays......Page 406 Delayed-type Hypersensitivity Response......Page 408 Iron Toxicosis......Page 409 Concurrent Exposure of Heavy Metals......Page 410 Concluding Remarks and Future Directions......Page 411 References......Page 412 Part III: Chemical Agents, Solvents and Gases Toxicity Biomarkers ......Page 414 Federal Food, Drug, and Cosmetic Act......Page 465 Organophosphates......Page 958 The Use of Novel Biomarkers of Toxic Solvent and Gas Exposure......Page 422 Mother–Infant/Child Pairs......Page 425 Paraquat......Page 434 References......Page 801 65. Proteomics in Biomarkers of Chemical Toxicity......Page 1102 Mechanism of Toxicity......Page 441 Acute Toxicity......Page 442 Urate......Page 690 Chronic Toxicity......Page 444 Chlorinated Hydrocarbons......Page 445 Biomarkers......Page 446 Pyrethrins and Pyrethroids......Page 447 Mechanism of Toxicity......Page 448 Biomarkers of Susceptibility......Page 453 INTRODUCTION......Page 461 Microtubules......Page 699 Triazines and Triazoles......Page 466 Fractalkine......Page 893 Citrulline in Diabetes......Page 469 Bipyridyl Derivatives......Page 470 Hereditary Breast and Ovarian Syndrome......Page 471 DNA Adducts......Page 472 Biomarkers in Acetaminophen Hepatotoxicity......Page 641 Dialkyldithiocarbamates......Page 473 Anilinopyrimidines......Page 474 Chloroalkylthiodicarboximides (Phthalimides)......Page 476 Halogenated Substituted Monocyclic Aromatics......Page 478 Concluding Remarks and Future Directions......Page 480 Prostate-Specific Antigen......Page 484 Physicochemical Properties......Page 487 PCP Study......Page 1093 Effects of Organic Solvents and Polybrominated Diphenyl Ethers on Microfilaments......Page 490 Concluding Remarks and Future Directions......Page 840 BIOMONITORING OF EXPOSURE TO RADIATION......Page 494 References......Page 598 Prevention and Treatment......Page 618 I......Page 498 Introduction......Page 502 New Advances in Biomonitoring, Exposure Science, Toxicology, Risk Assessment, and Decision-Making......Page 1086 Approaches to Biomarker Signature Characterization......Page 1050 Biomarkers of Susceptibility......Page 506 Acknowledgments......Page 507 References......Page 508 Introduction......Page 511 C......Page 813 Biomarkers of Exposure......Page 512 Estragole Study......Page 514 F......Page 1150 Comet Assay......Page 515 Biomarkers of Susceptibility......Page 516 Biomarkers of Susceptibility......Page 519 Biomarkers of Effects......Page 520 Chromium......Page 522 Thallium......Page 523 Biomarkers of Effects......Page 524 Biomarkers of Effects......Page 526 Current Concerns and Biological Relevance......Page 527 References......Page 528 31. Melamine......Page 532 Mechanism of Action......Page 533 Melamine Only Biomarkers......Page 536 References......Page 938 Tissue and Body Fluid Levels of Petroleum Hydrocarbons......Page 543 Morphologic Biomarkers......Page 546 Pesticides......Page 550 Individual Biomarkers and Aggregated Biomarker Signatures......Page 552 Adductomic......Page 554 Arginase-I......Page 639 Regulatory Mechanisms of miRNA Biogenesis......Page 812 DNA Damage and Genotoxicity......Page 562 Concluding Remarks and Future Directions......Page 563 Mass Spectrometry Analysis......Page 564 Introduction and Background......Page 567 Aldehydes as Lipid Peroxidation Products......Page 970 The Use of the Parent Compound as a Biomarker of Exposure......Page 569 Cylindrospermopsin......Page 571 The Use of Adducts as Biomarkers of Toxic Solvent and Gas Exposure......Page 572 Toxic Effects......Page 580 Mechanism of Action......Page 581 Biomarkers......Page 582 Chemistry......Page 583 Biomarkers......Page 584 Late-Occurring Health Effects Attributable to Radiation Exposure......Page 741 Grazing Management......Page 585 Effects of Organophosphorus Esters on Microfilaments......Page 586 Phytoestrogens and Cancer......Page 696 Biomarkers of Poisoning (Blood Alkaloid, Liver Alkaloid, Plant Fragment, or Rumen Sample)......Page 593 High Penetrance Genes Predisposing to Breast Cancer......Page 809 Toxicokinetics and Biotransformation of Ochratoxin A......Page 594 Gamma-Glutamyltranspeptidase......Page 596 Histopathological Biomarkers......Page 597 References......Page 599 37. Poisonous Plants: Biomarkers for Diagnosis......Page 603 INTRODUCTION......Page 604 Enzootic Hematuria......Page 903 Decreased Cerebrospinal Fluid Aβ42......Page 847 Elevated Cerebrospinal Fluid Total-Tau and Phospho-Tau......Page 605 Biomarkers of Poisoning (Clinical, Pathology, History of Ingestion, Methemoglobin)......Page 606 Toxicity......Page 607 Prevention of Poisoning......Page 608 Histology of Oral Mucosa......Page 609 Drug Intervention......Page 610 Toxicology......Page 611 Cattle Grazing......Page 612 Environmental Chemical Risk Assessment......Page 1081 DNA Methylation, Definitions, and Measurement Methods......Page 614 Prevention and Treatment......Page 617 Biomarkers of Poisoning (Blood or Ocular Calcium, Oxalate Analysis of Blood, History of Ingestion......Page 619 Kidney......Page 650 Biomarkers of Poisoning (Liver Enzymes, AST, LDH, GGTP, Cirrhosis, Histology, Pyrrole Analysis of Liver)......Page 621 Cytochrome c......Page 622 Toxicity of Death Camas to Livestock......Page 623 Clinical Signs......Page 624 CONCLUDING REMARKS AND FUTURE DIRECTIONS......Page 625 References......Page 626 Part V: Pharmaceuticals and Nutraceuticals Biomarkers ......Page 629 Proteomics......Page 856 Hydroxybutyrate Dehydrogenase......Page 636 Prostate Stem Cell Antigen......Page 836 Caspase-Cleaved K18......Page 642 Biomarkers for Drug-Induced Liver Injury in Tuberculosis–Human Immunodeficiency Virus–Infected Patients......Page 643 DAB2 Interacting Protein......Page 839 Biomarkers of Drug-Induced Vascular Injury......Page 644 Biomarkers for Monitoring Drug-Induced Vascular Injury......Page 645 Troponins......Page 646 Circulating Micro-RNAs......Page 647 Biomarkers in Drug Safety Evaluation......Page 649 Cystatin C......Page 651 Interleukin-18......Page 652 α2-Macroglobulin......Page 653 Lung......Page 654 Genetic and Genomic Biomarkers......Page 655 Biomarker Validation and Qualification......Page 656 Preclinical Qualification......Page 657 Clinical Qualification and Diagnostic Use......Page 658 Translational Safety Biomarker......Page 659 Concluding Remarks and Future Directions......Page 661 Regulatory Challenges......Page 669 The Risk Assessment......Page 670 Comet Formation......Page 671 Skin Neoplasia......Page 905 Banned Dietary Ingredients Causing Neurosuppression—Mitragyna speciosa (Kratom)......Page 673 Dessicated Thyroid Glandulars......Page 674 Assessing Susceptibility......Page 678 Concluding Remarks and Future Directions......Page 1110 Rotenone......Page 679 New Dietary Ingredients (Supplementation with Multiple, Combinations of Dietary Ingredients) Rauwolfia and Yohimbe Bark Extract......Page 681 Concluding Remarks and Future Directions......Page 683 Schizophrenia......Page 876 Grain-Based Diets......Page 689 Citrulline in Hypertension......Page 1032 High-Fructose/Sucrose Diets for Hypertriglyceridemia and Insulin Resistance......Page 692 Nonalcoholic Fatty Liver Disease......Page 693 Diets High in Sodium (and Fructose) for Hypertension......Page 694 Know Your Control Diet......Page 695 Other Compounds or Contaminants......Page 697 Pubertal Onset......Page 698 Part VI: Nanomaterials and Radiation ......Page 705 Organic Nanoparticles......Page 707 Organic Pollutants......Page 857 Cocaine......Page 960 Biomarkers of Lung Inflammation and Systemic Effects......Page 715 Toward Specific Biomarkers for Engineered Nanomaterials Exposure......Page 718 Acknowledgments......Page 720 References......Page 996 SOURCES OF RADIATION EXPOSURE......Page 729 PATH FORWARD......Page 749 References......Page 752 Lubricin......Page 894 New Scenarios to Assess Exposures and Effects: The Omics Approach......Page 762 Concluding Remarks and Future Directions......Page 765 Introduction......Page 773 Chromosomal Aberrations......Page 778 Chromosomal Aberrations and Their Mechanisms of Action......Page 782 Genetic Variability......Page 783 References......Page 785 DNA Methyltransferases......Page 789 Morphologic (Gross and Microscopic) and Clinical Pathology......Page 904 Histone Methylation......Page 792 Histone Phosphorylation......Page 793 Therapeutic Implications of Genetic Biomarkers......Page 810 Abnormalities in Histone Modifications......Page 797 Epigenetics and Cancer......Page 798 Testing for Genetic and Molecular Changes......Page 808 Moderate Penetrance Breast Cancer Genes......Page 811 2,3,7,8-Tetrachlorodibenzo-p-Dioxin......Page 1109 Exosomes......Page 814 67. Biomarkers in Epidemiology, Risk Assessment and Regulatory Toxicology......Page 818 Biomarkers in the Evaluation of a Pelvic Mass......Page 823 Biomarkers......Page 824 Flow Cytometry and Fluorescence-Activated Cell Sorting......Page 1051 Prostate Cancer Antigen 3......Page 833 Transmembrane Protease Serine 2-Erythroblast Transformation Specific–Related Gene Fusion Rearrangement......Page 835 References......Page 841 Elevated Cerebrospinal Fluid p-tau:Aβ42 Ratio......Page 849 18F-2-Deoxy-2-Fluoro-d-Glucose Positron Emission Tomography......Page 850 Genetic Biomarkers......Page 855 Humans......Page 890 Mitochondrial Dysfunction and Oxidative Stress Markers......Page 858 DJ-1......Page 859 8-OHG and 8-OHdG......Page 860 Oxidative Stress Due to High Dopamine Content in Methamphetamine-Induced Neurotoxicity......Page 870 Neuroinflammatory Mechanism in Meth-Induced Neurotoxicity......Page 872 Bipolar Disorder/Mood Disorder......Page 878 Animal Models in Neuropsychiatry......Page 879 Animal Models of Anxiety......Page 880 Animal Models of Schizophrenia......Page 881 Biomarkers of Bipolar Disorder and Schizophrenia......Page 882 Biomarkers of Schizophrenia......Page 883 References......Page 885 Introduction......Page 936 PATHOPHYSIOLOGY AND SIGNALING PATHWAYS IN OSTEOARTHRITIS......Page 887 D......Page 1147 TSG-6......Page 895 Mercury......Page 1063 Data Analysis Considerations......Page 896 Acknowledgments......Page 897 References......Page 898 Diagnostic Pathology......Page 902 Toxic Myopathy—Ionophore Toxic Syndrome......Page 907 Drug-Eluting Stents......Page 909 Glycogen Hepatopathy......Page 910 Metabolomics Biomarkers of Nanomaterials......Page 911 Copper Poisoning in Sheep......Page 912 Melamine Poisoning......Page 913 Polioencephalomalacia......Page 914 Nigropallidal Encephalomalacia in Horses......Page 915 Phospholipidosis......Page 916 Citrulline in Sickle Cell Anemia......Page 1031 References......Page 925 Lead......Page 927 Immunologically Mediated Oral Diseases......Page 928 Pemphigoid......Page 929 Oral Lichen Planus......Page 930 O......Page 931 Saliva: A Hidden Plethora of Biomarkers......Page 932 Concluding Remarks and Future Directions......Page 933 References......Page 934 Mitochondrial Dysfunction in Ischemia/Reperfusion......Page 942 Mitochondrial Dysfunction in Cancer......Page 945 Concluding Remarks and Future Directions......Page 947 In Vitro Models......Page 954 Lead......Page 957 Organochlorines and Pyrethrins/Pyrethroids......Page 959 Citrulline: Can It Improve Aerobic Function/Energy Production?......Page 1033 Epilepsy......Page 961 Citrulline as a Biomarker in Intrauterine Growth Retardation......Page 963 57. Biomarkers of Oxidative/Nitrosative Stress and Neurotoxicity......Page 968 Prostaglandin-Like Compounds as In Vivo Markers of Oxidative Stress......Page 969 References......Page 1121 Mercury......Page 980 References......Page 981 Arsenic......Page 988 Effects of Heavy Metals on Intermediate Filaments......Page 994 Database......Page 1005 Sample Preparation......Page 1006 Esophagus......Page 1008 miRNAs as Biomarkers of Pancreatic Toxicity......Page 1014 Liver......Page 1015 Heart......Page 1016 Brain......Page 1018 Role of miRNA in Arsenic-Induced Carcinogenesis......Page 1021 References......Page 1023 Citrulline as a Biomarker in Diseases......Page 1034 Citrulline as a Biomarker in Intestinal Disease......Page 1035 Citrulline: Is It a Reliable Biomarker in Critically Ill Patients?......Page 1036 Anticyclic Citrullinated Peptide Antibodies: A Novel Biomarker of Rheumatoid Arthritis......Page 1037 Citrulline as a Biomarker for Sjögren's Syndrome......Page 1039 Citrulline as a Biomarker in Transplants......Page 1040 Citrulline as a Biomarker in Critically Ill Patients and Correlation With Severity of Inflammation......Page 1041 Citrulline as a Biomarker of Ammonia Toxicity?......Page 1043 References......Page 1044 Biomarker Signatures in the -Omics era......Page 1055 Acknowledgments......Page 1057 References......Page 1058 Instrumental Analysis......Page 1062 Metabolomics Biomarkers in Hepatotoxicity......Page 1065 Metabolomics Biomarkers in Renal Toxicity......Page 1066 Metabolomics Biomarkers of Toxicity From Chemical Agents......Page 1068 Metabolomics Biomarkers of Biotoxins......Page 1070 Metabolomics Biomarkers of Drugs of Abuse......Page 1071 Transcriptomic Methods......Page 1076 Estragole Study......Page 1090 Biomarkers of Effect......Page 1130 Concluding Remarks and Future Directions......Page 1098 References......Page 1100 Lead......Page 1104 Diazinon......Page 1106 Glyphosate......Page 1107 Biological Samples Used for Biomonitoring Exposure Through Biomarkers......Page 1116 Introduction......Page 1123 Selenium......Page 1132 Formaldehyde......Page 1135 References......Page 1137 G......Page 1151 H......Page 1152 K......Page 1154 M......Page 1156 P......Page 1162 R......Page 1165 S......Page 1166 T......Page 1167 X......Page 1168 Z......Page 1169 Back Cover......Page 1170