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دانلود کتاب Biomarkers in Toxicology
دانلود کتاب نشانگرهای زیستی در سم شناسی
مشخصات کتاب
Biomarkers in Toxicology
ویرایش: 2
نویسندگان: Ramesh C. Gupta (editor)
سری:
ISBN (شابک) : 0128146559, 9780128146552
ناشر: Academic Press
سال نشر: 2019
تعداد صفحات: 1170
زبان: English
فرمت فایل : PDF (درصورت درخواست کاربر به PDF، EPUB یا AZW3 تبدیل می شود)
حجم فایل: 51 مگابایت
قیمت کتاب (تومان) : 46,000
در صورت تبدیل فایل کتاب Biomarkers in Toxicology به فرمت های PDF، EPUB، AZW3، MOBI و یا DJVU می توانید به پشتیبان اطلاع دهید تا فایل مورد نظر را تبدیل نمایند.
توجه داشته باشید کتاب نشانگرهای زیستی در سم شناسی نسخه زبان اصلی می باشد و کتاب ترجمه شده به فارسی نمی باشد. وبسایت اینترنشنال لایبرری ارائه دهنده کتاب های زبان اصلی می باشد و هیچ گونه کتاب ترجمه شده یا نوشته شده به فارسی را ارائه نمی دهد.
توضیحاتی در مورد کتاب نشانگرهای زیستی در سم شناسی
بیومارکرها در سم شناسی، ویرایش دوم، یک مرجع به موقع و جامع است که به تمام جنبه های نشانگرهای زیستی مربوط به قرار گرفتن در معرض مواد شیمیایی و اثرات آنها بر سیستم های بیولوژیکی اختصاص داده شده است. این نسخه اصلاح شده و کاملاً به روز شده شامل مدل های گونه های مهره داران و غیر مهره داران برای آزمایش سم شناسی و توسعه نشانگرهای زیستی است. این جلد مرجع که به چندین بخش کلیدی تقسیم شده است، شامل فصول جدیدی است که به موضوعات میکروپلاستیک، سمیت عصبی و مواد مغذی، همراه با نگاهی به آخرین فناوری‌های پیشرفته مورد استفاده برای شناسایی نشانگرهای زیستی اختصاص داده شده است. هر فصل حاوی چندین مرجع به ادبیات جاری و منابع مهم برای مطالعه بیشتر است.
با توجه به این درمان جامع، این کتاب یک مرجع ضروری برای هر کسی است که به نشانگرهای زیستی در زمینه‌های علمی و زیست پزشکی علاقه دارد.
- ادبیات گسترده را ارزیابی می‌کند و یک منبع را ارائه می‌کند که تمام جنبه‌های نشانگرهای زیستی سم‌شناسی را پوشش می‌دهد
- شامل فصل‌های کاملاً اصلاح‌شده، همراه با فصل‌های اضافی در مورد جدیدترین پیشرفت‌ها در این زمینه
- حساس ترین، دقیق ترین، منحصر به فرد ترین و معتبرترین نشانگرهای زیستی مورد استفاده به عنوان شاخص های قرار گرفتن در معرض را شناسایی و مورد بحث قرار می دهد
- موضوعات و کاربردهای بیومارکرهای خاص را پوشش می دهد، از جمله فصول مربوط به بیومارکرهای سم شناسی مولکولی، تجزیه و تحلیل نشانگرهای زیستی برای نانوسم شناسی، توسعه نشانگرهای زیستی برای دارو. ارزیابی اثربخشی، و خیلی بیشتر
توضیحاتی درمورد کتاب به خارجی
Biomarkers in Toxicology, Second Edition, is a timely and comprehensive reference dedicated to all aspects of biomarkers that relate to chemical exposure and their effects on biological systems. This revised and completely updated edition includes both vertebrate and non-vertebrate species models for toxicological testing and the development of biomarkers. Divided into several key sections, this reference volume contains new chapters devoted to topics in microplastics, neuroimmunotoxicity and nutraceuticals, along with a look at the latest cutting-edge technologies used to detect biomarkers. Each chapter contains several references to current literature and important resources for further reading.
Given this comprehensive treatment, this book is an essential reference for anyone interested in biomarkers across the scientific and biomedical fields.
- Evaluates the expansive literature, providing one resource covering all aspects of toxicology biomarkers
- Includes completely revised chapters, along with additional chapters on the newest developments in the field
- Identifies and discusses the most sensitive, accurate, unique and validated biomarkers used as indicators of exposure
- Covers special topics and applications of biomarkers, including chapters on molecular toxicology biomarkers, biomarker analysis for nanotoxicology, development of biomarkers for drug efficacy evaluation, and much more
فهرست مطالب
Cover Biomarkers in Toxicology Copyright Dedication Contributors Foreword Part I: Toxicity Testing Models and Biomarkers 1. Introduction References 2. Rodent Models for Toxicity Testing and Biomarkers Introduction The Rat Use in Toxicological Research Characteristics Strain Differences Normal Physiological Values Study Designs Routes of Test Article Administration Oral Routes Dietary Versus Gavage Methods Dietary Method Gavage Method Test Article Preparation Equipment Technique Neonatal Administration Capsule Water Intravenous Route Lateral Tail Vein Bolus Injection Tail Vein Infusions Jugular Vein Bolus Injection Infusion Saphenous, Lateral Marginal, and Metatarsal Veins Dorsal Penis Vein Sublingual Vein Intraperitoneal Route Intramuscular Route Subcutaneous Route Topical Route Rectal Route Intranasal Route Inhalation Route Intratracheal Administration Regimen End Point Measurement Techniques Observations and Physical Examinations Neurobehavioral Examination Functional Observational Battery Locomotor Activity Cardiovascular Parameters Electrocardiography Recording Methods Restraint Position Tethered Leads Telemetry ECG Waveform Heart Rate Blood Pressure Indirect Measurement Tail Cuff Method Hindpaw Method Direct Measurement Blood Collection Techniques Retro-Orbital Plexus Tail Tail Clip Venipuncture Arterial Puncture Cardiac Puncture Abdominal Aorta and Vena Cava Jugular Vein Proximal Saphenous and Metatarsal Vein Proximal Saphenous Vein Metatarsal Vein Sublingual Vein Decapitation Cannulation Jugular Vein Inferior Vena Cava Abdominal Aorta Subcutaneous Ports Urine Collection Necropsy Summary The Mouse Use in Toxicological Research Normal Physiological Values Species Differences Strain Differences Study Designs Acute Toxicity Studies Short-Term Toxicity Studies Chronic Toxicity Studies (26weeks–2years) Carcinogenicity Studies (18–24months) Teratology Studies Segment II Teratology Studies Genetic Toxicity Studies Mouse Micronucleus Assay Heritable Translocation Assay Microbial Host-Mediated Assay Special Studies Mouse Ear Swelling Test Dermal Carcinogenicity (Skin Painting) Study Routes of Test Substance Administration Oral Administration Gavage Description of Technique Dietary Admixtures Description of Technique Drinking Water Description of Technique Intravenous Injection Description of Technique Intraperitoneal Injection Description of Technique Intramuscular Injection Description of Technique Subcutaneous Injection Description of Technique Intradermal Injection Description of Technique Topical Administration Description of Technique Inhalation Chamber (Whole Body) Head/Nose Exposure (Head Only/Nose Only) End point Data Collection Clinical Observations and Physical Examinations Clinical Laboratory Evaluations Postmortem Procedures Summary The Hamster Species Syrian Hamster Chinese Hamster European Hamster Armenian Hamster Turkish Hamster Rumanian Hamster Dzungarian Hamster South African Hamster Spontaneous Tumors Animal Identification Dosing Procedures Oral Administration Subcutaneous Administration Intradermal Administration Intramuscular Administration Intraperitoneal Administration Intravenous Administration Blood Collection Techniques Retro-orbital Method Cardiac Puncture Tail Clipping Method Femoral Vein Method Jugular Vein Method Saphenous Vein Urine Collection Physical Parameters Neonatal Body Weights Body Weights and Weight Gains Dentition Life Spans Sexual Maturity Respiratory Rate and Oxygen Consumption Blood Pressure Heart Rate ECG Patterns Clinical Laboratory Glucose Lipids Urea Nitrogen Enzymes Alkaline Phosphatase Alanine Aminotransferase Aspartate Aminotransferase Creatine Kinase and Lactic Dehydrogenase Thyroid Hormones Reproductive Hormones Adrenal Hormones Proteins Hematology Values Erythrocytes Leukocytes Coagulation Trypanosomes Blood Gases and pH Urine Values Species Peculiarities Strain-Related Considerations Typical Study Protocols Carcinogenicity Toxicity Testing Inhalation and Intratracheal Studies Teratology Studies Toxicology Studies Chinese Hamster Ovary Cell Chromosome Aberrations Syrian Hamster Embryo Cell Transformation Assay Models of Diseases Cardiomyopathy Dental Caries Diabetes Mellitus Leprosy Muscular Dystrophy Osteoarthritis and Degenerative Joint Disease Pancreatic Cancer Concluding Remarks and Future Directions References 3. Göttingen Minipigs as Large Animal Model in Toxicology Pigs and Minipigs in Translational Research Legislation and Species Selection Göttingen Minipigs as an Animal Model Dosing Routes and Formulations Age and Sex Hematology Blood Biochemistry Organ Weight, Background Findings, and Comparative Aspects Safety Pharmacology Immune System Concluding Remarks and Future Directions References 4. Nonhuman Primates in Preclinical Research Introduction Clinical Pathology in NHPs Preanalytical Variation Hematology Coagulation and Hemostasis Clinical Biochemistry Urinalysis Background Microscopic Lesions in NHPs Mononuclear Cell Infiltrates Cardiovascular Gastrointestinal and Hepatic Renal Skeletal Muscle Concluding Remarks and Future Directions References 5. Biomarkers of Toxicity in Zebrafish Introduction Zebrafish Background Ecotoxicological Biomarkers of Toxicity Examples of Biomarkers of Fish Toxicity An Example of an Established Biomarker: Vitellogenin Cautions Concluding Remarks and Future Directions Acknowledgments References 6. Mechanistic Toxicology Biomarkers in Caenorhabditis elegans Introduction C. elegans and Biomarkers Mechanistic Biomarkers Oxidative Stress Markers Mitochondrial Markers Neurodegenerative Diseases and Gene–Environment Interactions Alzheimer's Disease Parkinson's Disease Concerns Unique to C. elegans Concluding Remarks and Future Directions Acknowledgments References 7. Potential of Small Animals in Toxicity Testing: Hope from Small World Introduction Toxicity Testing Using Small Animals Drosophila melanogaster Drosophila Model in the Prediction of Cellular Toxicity Prediction of Developmental, Reproductive, and Behavioral Toxicity Using Drosophila melanogaster Toxicomics Profiling Using Drosophila Predication of Toxicity Using Eisenia fetida Prediction of Toxicity Using Daphnia magna Concluding Remarks and Future Directions Acknowledgments References 8. Alternative Animal Toxicity Testing and Biomarkers INTRODUCTION USE OF ALTERNATIVES TO ANIMAL TESTING AND BIOMARKERS REASONS FOR DEVELOPING ALTERNATIVES TO ANIMAL TESTS AND BIOMARKERS EXAMPLES OF ORGANIZATIONS' RESEARCHING AND FUNDING ALTERNATIVES TO ANIMAL TESTING AND BIOMARKER DEVELOPMENT ACHIEVING 3RS WITH MINIMAL TO NO ANIMAL TESTING BY USING BIOMARKERS In Silico Computer Simulation In Vitro Cell Culture Techniques Limitations of Alternative In Vitro Tests APPLICATIONS OF IN VITRO TESTS AND BIOMARKERS Genetic Toxicology Testing, In Vitro Bacterial Mutation Assay (Ames Assay) In Vitro Micronucleus and Chromosome Aberration Assays in Cultured Cells (Cytogenetic Assays) Comet or Single-Cell Gel Electrophoresis Assay Integrated Genotoxicity Testing Using Fewer Animals and Collecting Most Information Unique Zebrafish Model In Vitro Pharmacologic Activity Testing Isolated Tissues Receptor Binding Studies In Vitro Drug Disposition Studies Major Challenges of In Vitro Absorption, Distribution, Metabolism, and Elimination Advances in Technologies Systemic Toxicity Testing in Product Development CONCLUDING REMARKS AND FUTURE DIRECTIONS References 9. Adverse Outcome Pathways and Their Role in Revealing Biomarkers Introduction Adverse Outcome Pathways: Principles of Development and Assessment Adverse Outcome Pathway Framework: Similarities and Differences With Biomarkers Adverse Outcome Pathways as a Tool to Retrieve Biomarkers Biomarkers Depicted from the Adverse Outcome Pathway–Knowledge Base Regulatory Use of Adverse Outcome Pathways Concluding Remarks and Future Directions References Part II: Systems Toxicity Biomarkers 10. Central Nervous System Toxicity Biomarkers Introduction Measuring Central Nervous System Dysfunctions Biomarkers in Neurotoxicology Biomarkers of Exposure Biomarkers of Susceptibility Biomarkers of Effects Case Study 1: The Organophosphorus Insecticides Toxicity and Neurotoxicity of Organophosphorus Biomarkers of Exposure Biomarkers of Susceptibility Biomarkers of Effect Case Study 2: Mild Traumatic Brain Injury Concluding Remarks and Future Directions Acknowledgments References 11. Peripheral Nervous System Toxicity Biomarkers Introduction Types of Biomarkers of the Peripheral Nervous System Peripheral Nervous System Biomarker Methodology Neurological and Physical Examination Protocol Sample Requirements for Biomarker Testing Biomedical Imaging and Informatics Electrodiagnostic Tests Blood Tests Testing for Toxins Molecular Diagnostics Molecular, Cellular, and Histological Techniques Toxicogenomics and Proteomics Approaches Metabonomics Biomarkers of Traumatic Brain Injury Affecting Peripheral Nervous System Biomarkers of Nerve Tissue Injury in the Peripheral Nervous System Biomarkers of Changes in Electrophysiology Ion Channels as Biomarkers Biomarkers of Axonal Injury Biomarkers of Altered Axonal Transport Biomarkers of Axonal Regeneration Potential Biomarkers of Pain Potential Biomarkers of Psychiatric Diseases, Neurodegenerative Diseases, and Insomnia Potential Biomarkers of Motor Function, Emotional Behavior, Temperature Regulation, Sensory Perception, Locomotion, and Psy ... Potential Biomarkers of Sleeping Disorders (Apnea, Insomnia, and Desynchronosis) Biomarkers of Peripheral Nervous System Infection MicroRNAs as Potential Biomarkers of Peripheral Nervous System Injury Chemical-Induced Peripheral Neuropathy Pharmacogenomic Biomarkers for Preventing Chemical-Induced Peripheral Neuropathy Epigenetic Biomarkers of Axonal Regeneration Biomarkers From Studies on Inherited Peripheral Neuropathies Multiple System Atrophy–Related Biomarkers Biomarkers of Demyelination Injuries Biomarkers of Neuromuscular Junction Injuries Biomarkers From Surrogate Tissue Analysis for Peripheral Nervous System Disorders Biomarkers of Cholinergic System and Its Relevance to the Peripheral Nervous System Peripheral Nervous System Biomarkers for Exposure to Organophosphates Biomarkers of Organophosphorus-Ester Induced Delayed Neurotoxicity Autonomic Nervous System Autoimmune Autonomic Disorders Autoantibodies as Biomarkers for Peripheral Nervous System Disorders Nonimmune Nodopathies Role of Peripheral Nervous System in Parkinson's Disease and Lewy Body Disease Neural Stress System of Peripheral Nervous System Biomarkers of Enteric Nervous System Emerging Avenues of Peripheral Nervous System Biomarker Developments: Exosomes Personalized Medicine Concluding Remarks and Future Directions References 12. Cardiovascular Toxicity Biomarkers Introduction Physiology of the Cardiovascular System Basic Functions Cardiac Cycle Nervous System Immune System Neurohormonal System Vascular System Xenobiotics Epigenetic Modifications Mitochondrial Dysfunction Proteomics Cardiac Toxicity Biomarker of Myocardial Ionic Dysfunction Electrocardiogram Metabolomics Biomarkers of Wall Stretch Natriuretic Peptide Choline Fatty Acid–Binding Protein Biomarkers of Necrosis Troponin Creatine Kinase Myoglobin Biomarkers of Inflammation C-Reactive Protein Galectin-3 Myeloperoxidase Tumor Necrosis Factor Remodeling ST2 and sST2 sST2 Soluble Matrix Metalloproteinase-9 Growth Differentiation Factor 15 Neurohormonal Action Fibrinogen Copeptin Vascular Biomarkers Homocysteine Lp-PLA2 Placental Growth Factor Pregnancy-Associated Plasma Protein-A Other Markers Heart Rate Variability Rho Kinase Plasma Ceramides Markers of Drug-Induced Toxicity Cardiac Biomarkers of Illegal Drugs, Chemicals, and Terror Agents Anthrax Pharmaceuticals Illegal Drugs Environmental Chemicals Weaponized Chemicals Future Trends in Cardiovascular Biomarkers MicroRNAs as Cardiac Biomarkers Risk Prediction of Cardiovascular Events Concluding Remarks and Future Directions References 13. Respiratory Toxicity Biomarkers Introduction The Respiratory System Causes of Lung Injury and Disease Types of Lung Injuries and Pathologies Acute Lung Injuries Asthma Bronchitis, Emphysema, and Chronic Obstructive Pulmonary Disease Pulmonary Fibrosis and Granuloma Pulmonary Hypertension Pulmonary Phospholipidosis Sampling Methods for Analysis of Biomarkers of Lung Toxicity Bronchoalveolar Lavage Sampling Sputum, Nasal Lavage, and Exhaled Breath Blood and Urine Sampling Types of Lung Toxicity Biomarkers Exposure Biomarkers Biochemical Biomarkers Biomarkers in Exhaled Breath Condensate Biomarkers in Bronchoalveolar Lavage Fluid, Nasal Lavage Fluid, and Sputum Total Protein and Albumin Activities of Lactate Dehydrogenase, γ-Glutamyltransferase, N-Acetylglucosaminidase, and Proteases/Antiproteinases Oxidation By-Products and Antioxidants Cytokines, Chemokines, and Growth Factors Bronchoalveolar Lavage Fluid Cells as a Determinant of Lung Inflammation Circulating Biomarkers of Lung Injury and Pathology Surfactant, Other Lung-Specific Proteins, and Immunological Biomarkers Collagen and Elastin Fragments Cytokines, Metalloproteases, and Acute-Phase Proteins Thrombosis Biomarkers Circulating Progenitor Cells Microparticles miRNA Biomarker Identification Using Proteomic and Metabolomic Profiling Biomarker Identification Using Genomic Profiling of Nucleated Blood Cells Urine Biomarkers of Lung Injury and Disease Concluding Remarks and Future Directions Acknowledgments Disclaimer References 14. Hepatic Toxicity Biomarkers Introduction Overview of Liver Physiology, Toxicity, and Pathology Bioactivation and Detoxification Protein Synthesis and Catabolism Bilirubin Processing Covalent Binding Necrosis and Apoptosis Inflammation (Immune) Hepatitis Steatosis Review of Existing Biomarkers of Liver Toxicity Alanine Aminotransferase Aspartate Aminotransferase Alkaline Phosphatase Total Bilirubin Other Existing Hepatotoxicity Biomarkers Review of Emerging Biomarkers Genetic Biomarkers of Hepatotoxicity Genomics Biomarkers of Hepatotoxicity Proteomic Biomarkers of Hepatotoxicity Metabolomics Biomarkers in Hepatotoxicity MicroRNAs as Biomarkers of Hepatotoxicity Biomarker Qualification and Validation Concluding Remarks and Future Directions References 15. Conventional and Emerging Renal Biomarkers Introduction Characteristics of Biomarkers Traditional Biomarkers Glomerular Filtration Rate Proteinuria Enzymuria Newer Biomarkers Cystatin C Neutrophil Gelatinase–Associated Lipocalin Kidney Injury Molecule-1 Interleukin 18 Liver-type Fatty Acid Binding Protein Genomics, Proteomics, Metabolomics Concluding Remarks and Future Directions References 16. Gastrointestinal Toxicity Biomarkers Introduction NSAID-Induced Gastrointestinal Toxicity Chemotherapy-induced Gastrointestinal Toxicity Radiation-induced Gastrointestinal Toxicity Inflammatory Bowel Diseases Biomarkers for Gastrointestinal Damage Blood Biomarkers Citrulline Diamine Oxidase CD64 Gastrins C-reactive Protein Orally Administered Probes Matrix Metalloproteinases Pepsinogen I and II Fecal Biomarkers Calprotectin Lactoferrin Polymorphonuclear Neutrophil Elastase Bile Acids I-FABP and L-FABP MicroRNA Fecal S100A12 Other Novel Approaches Concluding Remarks and Future Directions Metabolome-based Biomarkers References 17. Reproductive Toxicity Biomarkers Introduction Male Reproductive Biomarkers Spermatogenesis Synthesis of Steroids, Gonadotropins, and Peptide Hormones in Males Male Puberty Male Reproductive Aging Female Reproductive Biomarkers Folliculogenesis Synthesis of Steroids, Gonadotropins, and Peptide Hormones in Females Female Puberty Uterus Placenta Female Reproductive Aging Concluding Remarks and Future Directions References 18. Biomarkers of Toxicity in Human Placenta Introduction Placental Development and Structure Toxic and Hormonally Active Chemicals in Human Placenta Placental Functions and Molecular Pathways Involved in Toxicity Xenobiotic Metabolism and Its Regulation in Human Placenta Placental Transporters Placental Hormone Production Molecular Stress Protein Pathways Involved in Toxicity of Human Placenta Possibilities for Studying Pathways and Proteins Involved in Toxicity of Human Placenta Potential Biomarkers of Exposure and Toxicity in Human Placenta Toxic Compounds and Their Metabolites as Biomarkers Placental DNA Adducts as Biomarkers Xenobiotic-Metabolizing Enzymes, Placental Hormones, and Stress-Related Proteins as Biomarkers of Exposure and/or Toxicity ... Epigenetic Changes in Human Placenta as Potential Biomarkers of Toxicity Use of Placenta in Regulatory Toxicology—Considerations by Ecvam and Other Organizations OECD Guidelines Role of European Center for the Validation of Alternative Methods Experimental Methods Concerning Placenta Concluding Remarks and Future Directions References 19. Early Biomarkers of Acute and Chronic Pancreatitis Introduction Anatomical, Physiological, and Metabolic Considerations for Pancreatic Injury Acute Pancreatitis Chronic Pancreatitis Biomolecular Basis of Pancreatitis Biomarkers of Acute and Chronic Pancreatitis Abdominal Imaging Techniques Functional Biomarkers of Endocrine and Exocrine Pancreatitis Amylase Isoamylase Lipase Carbohydrate-Deficient Transferrin Activation By-Products of Pancreatic Trypsinogen and Carboxypeptidase B Elastase and Phospholipase A2 Procalcitonin C-Reactive Protein and Pancreatitis-Associated Protein Cathepsins Peptides Inflammatory Cytokines and Chemokines Biomarkers of Endocrine and Autoimmune Pancreatitis Ethanol Metabolites and Conjugates Differentially Altered Proteins, Metabolites, Small Molecules, and microRNA Comparison of Biomarkers Between Acute and Chronic Pancreatitis Biomarkers for Early Detection of Pancreatic Cancer Breathe Analysis Concluding Remarks and Future Directions References 20. Skeletal Muscle Toxicity Biomarkers Introduction Muscle Types Pesticides Cholinesterase Inhibitors Behavioral Effects Cholinergic Effects Noncholinergic Effects Excitotoxicity and Oxidative/Nitrosative Stress Creatine Kinase and Creatine Kinase Isoenzymes Lactate Dehydrogenase and Lactate Dehydrogenase Isoenzymes Histopathological Alterations Strychnine Paraquat Metals Therapeutic Drugs Lipid-Lowering Drugs Drugs Used Against AIDS Antiinflammatory Drugs Antitumor and Anticancer Drugs Drugs of Abuse Venoms and Zootoxins Snake Toxins Spider Venom Botulinum Toxin Myotoxic Plants Concluding Remarks and Future Directions References 21. Ocular Biomarkers in Diseases and Toxicities Introduction Ocular Biomarkers Molecular Biomarkers in Ocular Surface Disease Molecular Biomarkers in Keratoconus Molecular Biomarkers in Glaucoma Molecular Biomarkers in Retinal Disease Molecular Biomarkers in Age-Related Macular Degeneration Molecular Biomarkers in Ocular Oncology Systemic Agents and Ocular Toxicity Concluding Remarks and Future Directions References 22. Biomarkers of Ototoxicity Introduction Structure and Function of the Normal Auditory System Anatomic Structure of the Human Auditory System Hearing Mechanisms Overview on Ototoxicity Classification of Chemicals Causing Ototoxicity Pharmaceuticals Antibiotics Aminoglycosides Macrolides Salicylates and Nonsteroidal Antiinflammatory Drugs Antineoplasic Drugs Cisplatin Vincristine Loop Diuretics Antimalarial Drugs Phosphodiesterase Type 5 Inhibitors Antiepileptic Drugs Industrial Chemicals Factors Modifying Chemical Ototoxicity Underlying Mechanisms of Ototoxicity Functional and Molecular Biomarkers for the Evaluation of Ototoxicity Functional Assessment of the Hearing Damage Pure-Tone Audiometric Testing Distortion Product Otoacoustic Emission Acoustic Immitance Test Acoustic Brain Stem Response Testing Molecular Biomarkers Alternative Models Concluding Remarks and Future Directions References 23. Blood and Bone Marrow Toxicity Biomarkers Introduction Hematopoietic System Bone Marrow Hematopoiesis Hematopoietic Cells Erythrocytes Platelets Monocytes Neutrophils Eosinophils Basophils Lymphocytes Soluble Mediators Mechanisms of Hematotoxicity Biomarkers of Hematotoxicity Markers of Hematopoietic/Hematologic Toxicity Complete Blood Count Markers of Erythrocyte Toxicity Markers of Platelet Toxicity Markers of Bone Marrow Toxicity Bone Marrow Evaluation Progenitor Cell Colony Formation Markers of Hemostatic Toxicity Concluding Remarks and Future Directions References 24. Immunotoxicity Biomarkers Introduction The Immune System Lymphoid Organs and Tissues Cells of the Immune System B Cell Lymphocytes T Cell Lymphocytes Neutrophils Macrophages Natural Killer Cells Mast Cells Soluble Mediators of Immunity Cytokines Chemokines Other Soluble Mediators Mechanisms of Immunotoxicity Biomarkers Biomarkers of Immune Status Cell Counts Organ Weight Histopathology Antibody Assays T-dependent Antibody Response Delayed-type Hypersensitivity Response Lymphocyte Phenotyping Natural Killer Cell Activity Phagocytosis and Chemotaxis Proliferation Tests Cytokine Profiling Other Soluble Mediators Biomarkers of Hypersensitivity Local Lymph Node Assay Human Repeat-Insult Patch Test Immunoglobulin E Levels Biomarkers of Autoimmunity Concluding Remarks and Future Directions References Part III: Chemical Agents, Solvents and Gases Toxicity Biomarkers 25. Bisphenol A Biomarkers and Biomonitoring INTRODUCTION BISPHENOL A BIOMARKER ISSUES IN BIOMONITORING EXPOSURE AND SELECTED OUTCOME STUDIES LARGE GENERAL POPULATION BIOMONITORING PROGRAMS National Health and Nutrition Examination Survey, United States Canadian Health Measures Survey Generation R Study, The Netherlands Norwegian Mother and Child Cohort Study, Norway Other General Population Exposure Studies in Various Countries PREGNANT WOMEN, MOTHER–INFANT/CHILD PAIRS, INFANTS, CHILDREN Pregnant Women Mother–Infant/Child Pairs Children FOOD PACKAGING AND BISPHENOL A ALTERNATIVES CONCLUDING REMARKS AND FUTURE DIRECTIONS References 26. Insecticides Introduction Organophosphates and Carbamates Mechanism of Toxicity Biomarkers Acute Toxicity Intermediate Syndrome Delayed Toxicity Chronic Toxicity Chlorinated Hydrocarbons Mechanism of Toxicity Biomarkers Pyrethrins and Pyrethroids Mechanism of Toxicity Biomarkers Amitraz Mechanism of Toxicity Biomarkers Neonicotinoids Mechanism of Toxicity Biomarkers Fipronil Mechanism of Toxicity Biomarkers Ivermectin and Selamectin Mechanism of Toxicity Ivermectin Selamectin Biomarkers Rotenone Mechanism of Toxicity Biomarkers Concluding Remarks and Future Directions References 27. Herbicides and Fungicides INTRODUCTION BACKGROUND TOXICOKINETICS MECHANISM OF ACTION BIOMARKERS AND BIOMONITORING OF EXPOSURE Herbicides Phenoxy Acid Derivatives Triazines and Triazoles Phenylurea Herbicides Protoporphyrinogen Oxidase–Inhibiting Herbicides Substituted Anilines Bipyridyl Derivatives Amides and Acetamides Imidazolinones Triazolopyrimidine Phosphonomethyl Amino Acids or Inhibitors of Aromatic Acid Biosynthesis Others Fungicides Dialkyldithiocarbamates Anilinopyrimidines Chloroalkylthiodicarboximides (Phthalimides) Halogenated Substituted Monocyclic Aromatics CONCLUDING REMARKS AND FUTURE DIRECTIONS References 28. Polychlorinated Biphenyls, Polybrominated Biphenyls, and Brominated Flame Retardants Introduction Polychlorinated Biphenyls Physicochemical Properties and Environmental Levels Human Health Effects and Modes of Action Polybrominated Biphenyls Physicochemical Properties Human Health Effects and Modes of Action Brominated Flame Retardants Physicochemical Properties Human Health Effects and Modes of Action Thyroid Hormone Disruption as a Biomarker of Exposure and Effect Perturbed Calcium Homeostasis and Kinase Signaling as Biomarkers of Effect Induction of Cytochrome P450 Enzymes as a Biomarker of Exposure and Effect Concluding Remarks and Future Directions Acknowledgments References 29. Polycyclic Aromatic Hydrocarbons Introduction Biomarkers of Exposure Hydroxylated Metabolites DNA Adducts Protein Adducts Other Biomarkers of Exposure Biomarkers of Effect Genetic Alterations Biomarkers of Susceptibility Concluding Remarks and Future Directions Acknowledgments References 30. Metals Introduction Classification of Biomarkers Selection of an Ideal Biomarker: Benefits and Drawbacks Biomonitoring of Exposure to Heavy Metals Lead Biomarkers of Exposure Biomarkers of Effects Biomarkers of Susceptibility Arsenic Biomarkers of Exposure Biomarkers of Effects Biomarkers of Susceptibility Mercury Biomarkers of Exposure Limitations of Biomarkers of Exposure Biomarkers of Effects Biomarkers of Susceptibility Cadmium Biomarkers of Exposure Biomarkers of Effects Biomarkers of Susceptibility Chromium Biomarkers of Exposure Biomarker of Effects Biomarkers of Susceptibility Thallium Biomarkers of Exposure Biomarkers of Effects Biomarkers of Susceptibility Manganese Biomarkers of Exposure Biomarkers of Effects Biomarkers of Susceptibility Concurrent Exposure of Heavy Metals Current Concerns and Biological Relevance Concluding Remarks and Future Directions References 31. Melamine Introduction and Historical Background Toxicology of Melamine Toxicity Pharmacokinetics/Toxicokinetics Mechanism of Action Treatment Biomarkers Melamine+Cyanuric Acid Biomarkers Melamine Only Biomarkers Concluding Remarks and Future Directions References 32. Biomarkers of Petroleum Products Toxicity Introduction Chemical Markers Polycyclic Aromatic Hydrocarbons Tissue and Body Fluid Levels of Petroleum Hydrocarbons Biochemical Biomarkers CYP Biomarkers Biomarkers of Responses to Oxidate Stress Genetic Biomarkers of Petroleum Exposure Morphologic Biomarkers Teratology Biomarkers in Birds Concluding Remarks and Future Directions References 33. Biomarkers of Chemical Mixture Toxicity Introduction Potential Chemical Mixtures Pesticides Organochlorinated Compounds Halogenated Flame Retardants Polycyclic Aromatic Hydrocarbons Metals Biomonitoring for Assessing Human Exposure to Chemical Mixtures Biological Specimens Blood Urine New Matrices for Assessing Cumulative Exposure Milk Saliva Hair Meconium Biomolecular Adducts Risk Assessment of Combined Actions of Chemical Mixtures Biomarkers of Target Organ Toxicity of Chemical Mixtures Biomarkers of Liver Damage Kidney Nervous System Lungs Nonspecific Biomarkers of Toxic Response Oxidative Stress DNA Damage and Genotoxicity Concluding Remarks and Future Directions References 34. Biomarkers of Toxic Solvents and Gases Introduction Solvents Gases Biomarkers of Toxic Solvent and Gas Exposure The Use of the Parent Compound as a Biomarker of Exposure The Use of Metabolites of Toxic Solvents or Gases as Biomarkers of Exposure The Use of Adducts as Biomarkers of Toxic Solvent and Gas Exposure The Use of Novel Biomarkers of Toxic Solvent and Gas Exposure Biomarkers of Effects of Toxic Solvent and Gas Exposure Interpretation and Use of Biomonitoring Data Concluding Remarks and Future Directions References Part IV: Biotoxins Biomarkers 35. Freshwater Cyanotoxins Introduction Hepatotoxins Microcystins Introduction Chemistry Toxic Effects Cellular Transport Mechanism of Action Biomarkers Cylindrospermopsin Introduction Chemistry Toxic Effects Mechanism of Action Biomarkers Neurotoxins Anatoxin-a Introduction Chemistry Toxic Effects Mechanism of Action Biomarkers Anatoxin-a(s) Introduction Chemistry Toxic Effects Mechanism of Action Biomarkers Saxitoxins Introduction Chemistry Toxic Effects Mechanism of Action Biomarkers Concluding Remarks and Future Directions References 36. Mycotoxins Introduction Aflatoxins Background Chemistry and Legal Regulation of Aflatoxins Toxicokinetics of Aflatoxins Aflatoxin Metabolism and Chemical Biomarkers of Aflatoxin Exposure Histopathological Biomarkers of Exposure to Aflatoxins Sterigmatocystin Ochratoxins Production and Occurrence Toxicokinetics and Biotransformation of Ochratoxin A Chemical Biomarkers of Ochratoxin A Histopathologic Biomarkers of Exposure to Ochratoxins A Fumonisins Chemistry of Fumonisins Toxicokinetics, Metabolism, and Chemical Biomarkers Histopathological Biomarkers Deoxynivalenol Trichothecene Toxicokinetics, Biotransformation, and Biomarkers Zearalenone Background Toxicokinetics, Biotransformation, and Biomarkers Concluding Remarks and Future Directions References 37. Poisonous Plants: Biomarkers for Diagnosis INTRODUCTION ASTRAGALUS AND OXYTROPIS SPECIES (LOCOWEEDS, NITROTOXIN SPP., AND SELENIUM ACCUMULATORS) Locoweeds Toxicology Toxin Conditions of Grazing Biomarkers of Poisoning (AST, GGTP, White Cell Count, Cellular Vacuolation, Serum Swainsonine, α-Mannosidase) Prevention of Poisoning and Management Recommendations Nitro-Containing Astragalus (Milkvetches) Toxicology Biomarkers of Poisoning (Clinical, Pathology, History of Ingestion, Methemoglobin) Prevention and Treatment Seleniferous Astragalus Toxicity Biomarkers of Poisoning (Liver Biopsy Se, Whole Blood Se, Enzyme, Hair, Mane, Tail, Hoof Samples) Prevention of Poisoning LARKSPURS (DELPHINIUM SPP.) Toxicology Biomarkers of Poisoning (Blood Alkaloid, Liver Alkaloid, Plant Fragment, or Rumen Sample) Prevention and Management of Poisoning Grazing Management Drug Intervention LUPINES (LUPINUS SPP.) Toxicology Cattle Grazing Biomarkers of Poisoning (Clinical Effects, History of Ingestion, Serum Analysis, Liver, Urine, Crooked Calf Syndrome (CCS)) Prevention, Management, and Treatment POISON HEMLOCK (CONIUM MACULATUM) Toxicology Biomarkers of Poisoning Prevention and Treatment WATER HEMLOCK (CICUTA SPP.) Toxicology Biomarkers of Poisoning (Blood Enzymes, CPK, AST, GGTP, Histological Lesions in the Heart, Long Muscles, Clinical Signs, Hi ... Prevention and Treatment PONDEROSA PINE NEEDLES (PINUS SPP.) Toxicology Biomarkers of Poisoning (Premature Parturition; Live-Premature Calf; Retained Fetal Membrane; Agathic or Tetrahydroagathic ... Prevention and Treatment RAYLESS GOLDENROD (ISOCOMA PLURIFLORA) White Snakeroot (Eupatorium rugosum) Toxicology Biomarkers of Poisoning (Blood Enzymes, CPK, Troponin, Histology, Lesions in Heart, Long Muscles, Clinical Signs, History o ... Prevention and Treatment HALOGETON (HALOGETON GLOMERATUS) Toxicology Treatment of Poisoned Animals Biomarkers of Poisoning (Blood or Ocular Calcium, Oxalate Analysis of Blood, History of Ingestion Management to Prevent Poisoning PYRROLIZIDINE ALKALOID-CONTAINING PLANTS Toxicology Biomarkers of Poisoning (Liver Enzymes, AST, LDH, GGTP, Cirrhosis, Histology, Pyrrole Analysis of Liver) Prevention and Treatment PHOTOSENSITIZING PLANTS Toxicology Primary Secondary Biomarkers of Poisoning (Bilirubin, Liver Enzymes, Skin Biopsies, History of Ingestion) Prevention and Treatment DEATH CAMAS Toxicity of Death Camas to Livestock Biomarkers of Poisoning (Alkaloid Analysis of Serum, Liver, Pathology, History of Ingestion) Management and Prevention KNAPWEEDS: CENTAUREA SPP. Toxicology Clinical Signs Biomarkers of Poisoning (History of Ingestion, Pathology Brain Lesions, Horses Only) Prevention and Treatment CONCLUDING REMARKS AND FUTURE DIRECTIONS References Part V: Pharmaceuticals and Nutraceuticals Biomarkers 38. Biomarkers of Drug Toxicity and Safety Evaluation Introduction Clinical Drug Development Application of Biomarkers in Postmarketing Integration and Use of Safety Biomarkers in Drug Development Application of Safety Biomarkers in Different Phases of Drug Development Traditional Indicator for Drug Toxicity Assessment Alkaline Phosphatase Creatine Kinase Aminotransferases Lactate Dehydrogenase Bilirubin Creatinine and Blood Urea Nitrogen Plasma Proteins Total Protein Gamma-Glutamyltranspeptidase Hydroxybutyrate Dehydrogenase Lactate Dehydrogenase Sodium, Potassium, and Chloride Urinalysis Biomarkers of Drug Liver Toxicity Biomarker for Monitoring Liver Injury Alanine Aminotransferase and Its Two Isoforms Glutamate Dehydrogenase Serum F Protein Arginase-I New Biomarkers for Monitoring Liver Injury Alpha-Glutathione S-transferase Gamma-Glutamyl Transpeptidase Sorbitol Dehydrogenase Purine Nucleotide Phosphorylase Malate Dehydrogenase Paraoxonase-1 Biomarkers in Acetaminophen Hepatotoxicity High Mobility Group Protein B1 Caspase-Cleaved K18 Glutathione S-Transferase Alpha Malate Dehydrogenase Cytochrome c Biomarkers for Drug-Induced Liver Injury in Tuberculosis–Human Immunodeficiency Virus–Infected Patients Biomarker of Drug-Induced Kidney Toxicity Urinary β2-Microglobulin Biomarkers of Drug-Induced Vascular Injury Biomarkers for Monitoring Drug-Induced Vascular Injury Biomarkers of Drug-Induced Cardiac Injury Monoclonal Antibodies Troponins B-type Natriuretic Protein Circulating Micro-RNAs Biomarkers of Drug-Induced Brain Injury Biomarkers in Drug Safety Evaluation Importance of Understanding Specific Mechanisms of Toxicity in Drug Development Biomarkers in Drug Safety Evaluation Safety Biomarkers for Preclinical and/or Clinical Perspectives Kidney Kidney Injury Molecule-1 β2-Microglobulin Cystatin C Clusterin Trefoil Factor 3 Other Kidney Biomarkers Lipocalin-2 N-Acetyl-β-d-Glucosaminidase Interleukin-18 Matrix Metalloproteinase-9 Netrin-1 Monocyte Chemotactic Peptide-1 Liver Heart α2-Macroglobulin Ultrasound Others Novel Biomarkers C-Reactive Protein Galectin-3 Matrix Metalloproteinases Tissue Inhibitors of Metalloproteinases Lung Lipid/Carbohydrate Metabolism Central Nervous System Genetic and Genomic Biomarkers Biomarker Validation and Qualification Identification of Safety Biomarkers Preclinical Qualification Clinical Qualification and Diagnostic Use Translational Safety Biomarker Concluding Remarks and Future Directions References 39. Risk Assessment, Regulation, and the Role of Biomarkers for the Evaluation of Dietary Ingredients Present in Dietary Supple ... Introduction Overview of Regulation of Dietary Supplements in the United States Federal Food, Drug, and Cosmetic Act Regulatory Challenges Dietary Ingredient Safety The Risk Assessment Hazard Identification Hazard Characterization Exposure Assessment Risk Characterization Biomarkers of Toxicity: Dietary Ingredients Biomarkers Associated with the Presence of Banned Ingredients Banned Dietary Ingredients Causing Neurostimulation—Ephedrine Alkaloids Banned Dietary Ingredients Causing Neurosuppression—Mitragyna speciosa (Kratom) Biomarkers Associated with the Presence of Endocrine Disruptors Dessicated Thyroid Glandulars Biomarkers Associated With the Presence of Carcinogens Aristolochic Acid Pyrrolizidine Alkaloids—Symphytum Spp. (Common Name, Comfrey) Biomarkers of Toxicity: New Dietary Ingredients Premarket Notification of a New Dietary Ingredient Premarket Notification for New Dietary Supplement as Enhancers of Metabolism, Energy, and Weight Loss Usnic Acid Biomarkers of Toxicity: New Dietary Ingredients Active Moiety of a New Dietary Ingredient Red Yeast Rice—Monacolin K and Statin Activity Biomarkers of Toxicity: New Dietary Ingredients Safety Assessment of Multiple Dietary Ingredients in a Dietary Supplement New Dietary Ingredients (Supplementation with Multiple, Combinations of Dietary Ingredients) Rauwolfia and Yohimbe Bark Extract New Dietary Ingredients (Supplementation with Multiple, Combinations of Dietary Ingredients)—Galantamine and Huperzine A (C ... Concluding Remarks and Future Directions References 40. Nutriphenomics in Rodent Models: Impact of Dietary Choices on Toxicological Biomarkers Introduction Dietary Choices Grain-Based Diets Purified Diets Diet-Induced Metabolic Disorders High-Fat Diets for Diet-Induced Obesity Models Diet-Induced Atherosclerosis/Hypercholesterolemia Models Mice and Rats Hamsters Guinea Pigs High-Fructose/Sucrose Diets for Hypertriglyceridemia and Insulin Resistance Nonalcoholic Fatty Liver Disease Diets High in Sodium (and Fructose) for Hypertension Metabolic Disease Development and the Importance of Fiber Type Know Your Control Diet Potential Effects of Grain-Based Diets and Low-Fat Purified Diets on the Rodent Phenotype Grain-Based Diets Phytoestrogens and Development/Maturation Phytoestrogens and Cancer Arsenic and Heavy Metals Other Compounds or Contaminants Purified Low-Fat Diets and Health Status of Rodents Kidney Calcinosis Pubertal Onset Metabolic Effects Concluding Remarks and Future Directions References Part VI: Nanomaterials and Radiation 41. Engineered Nanomaterials: Biomarkers of Exposure and Effect Introduction and Background Classification and Characteristics of Nanomaterials Carbon-Based Nanoparticles: Fullerenes Inorganic Nanoparticles Organic Nanoparticles Toxicity Testing of Nanomaterials Definition and Meaning of Biological Monitoring and Its Application to Engineered Nanomaterials Challenges of the Development of Biomarkers of Exposure to Engineered Nanomaterials Due to Their Biokinetics Biological Interactions Relevant to Biomarkers of Exposure to Engineered Nanomaterials at Molecular, Cellular, and Organ Level Examples of Given Biomarkers Biomarkers of Exposure Biomarkers of Effect Biomarkers of Lung Inflammation and Systemic Effects Biomarkers of Oxidative DNA Damage and RNA Methylation Toward Specific Biomarkers for Engineered Nanomaterials Exposure Concluding Remarks and Future Directions Acknowledgments References 42. Biomarkers of Exposure and Responses to Ionizing Radiation INTRODUCTION KEY DEFINITIONS AND UNITS RADIATION PROTECTION SYSTEM SOURCES OF RADIATION EXPOSURE HISTORICAL PERSPECTIVE Personal Experience BIOMONITORING OF EXPOSURE TO RADIATION Radiation-Attributable Disease Late-Occurring Health Effects Attributable to Radiation Exposure PATH FORWARD Dedication and Acknowledgments References Part VII: Carcinogens Biomonitoring and Cancer Biomarkers 43. Biomonitoring Exposures to Carcinogens Introduction Assessing Exposures Chemicals and Metabolites DNA and Protein Adducts Assessing Effects Chromosomal Aberrations and Sister Chromatid Exchanges Micronuclei Comet Assay Specific Gene Mutations Telomere Shortening Epigenetic Changes Assessing Susceptibility New Scenarios to Assess Exposures and Effects: The Omics Approach Adductomic Transcriptomics Epigenomic Metabolomic Concluding Remarks and Future Directions References 44. Genotoxicity Biomarkers: Molecular Basis of Genetic Variability and Susceptibility Introduction Genotoxic Biomarker Detection Methods In Silico Approaches In Vitro and In Vivo Biomarkers of Genotoxicity Gene Mutations in Prokaryotes Micronucleus Formation Chromosomal Aberrations Comet Formation Toxicogenomic Signatures Other Genotoxic Biomarker Detection Methods Biomarkers and Mechanism of Action Gene Mutations and Their Mechanism of Action Chromosomal Aberrations and Their Mechanisms of Action Molecular Basis of Genetic Variability and Susceptibility Genetic Variability Susceptibility Concluding Remarks and Future Directions References 45. Epigenetic Biomarkers in Toxicology Introduction DNA Methylation Pathways of DNA Methylation DNA Methyltransferases Transcriptional Repression and DNA Methyl-Binding Proteins Histone Modifications Histone Acetylation Histone Methylation Histone Phosphorylation Histone Ubiquitination and Sumoylation Polycomb and Trithorax Proteins Noncoding RNA Epigenetics and Disease Abnormalities of DNA Methylation Abnormalities in Histone Modifications Epigenetics and Cancer Epigenetics and Autoimmune Disease Systemic Lupus Erythemosus Type 1 Diabetes Mellitus Epigenetics and Metabolic Syndrome Concluding Remarks and Future Directions References 46. Risk Factors as Biomarkers of Susceptibility in Breast Cancer Introduction Epidemiology Pathology Risk Factors Life Stage–Related Risks Gestation and Development of the Fetus Puberty Pregnancy Lactation and Breastfeeding Family History Genetic Modifications History of Benign Conditions Prognostic Factors Detection and Screening Tumor Marker Analysis Testing for Genetic and Molecular Changes Syndromes Predisposing to Breast Cancer Hereditary Breast and Ovarian Syndrome High Penetrance Genes Predisposing to Breast Cancer Therapeutic Implications of Genetic Biomarkers Other Highly Penetrant Breast Cancer Predisposing Genes Moderate Penetrance Breast Cancer Genes Low Penetrance Breast Cancer Polygenes DNA Methylation, Definitions, and Measurement Methods Impact of Methylation Biomarkers DNA Methylation Markers and Primary Prevention DNA Methylation Markers for Secondary Prevention and Early Detection DNA Methylation Markers and Tertiary Prevention and Role in Prognosis Male Breast Cancer Susceptibility Factors Epidemiology Pathology Risk Factors Cancer Aggressiveness Risk Factors Impact of Cancer Aggressiveness Risk Factors for Patient Management and Health Policies References 47. Pancreatic and Ovarian Cancer Biomarkers Introduction Currently Used Clinical Biomarkers Cancer Antigen 19-9 in Pancreatic Cancer Cancer Antigen-125 in Ovarian Cancer Diagnostic Biomarkers Pancreatic Cancer Ovarian Cancer Biomarkers in the Evaluation of a Pelvic Mass Prognostic Biomarkers Pancreatic Cancer Ovarian Cancer Predictive Biomarkers Pancreatic Cancer Ovarian Cancer Concluding Remarks and Future Directions References 48. Prostate Cancer Biomarkers Introduction Screening and Early Detection for Prostate Cancer Contemporary Clinical Biomarkers in Prostate Cancer Prostate-Specific Antigen Additional Serum Testing Prostate Cancer Antigen 3 Candidate Biomarkers for Prostate Cancer ConfirmMDx Test Cell Cycle Progression Signature Test Oncotype DX Test Transmembrane Protease Serine 2-Erythroblast Transformation Specific–Related Gene Fusion Rearrangement Glutathione S-transferase P1 α-Methylacyl Coenzyme A Racemase Chromogranin A Prostate-Specific Membrane Antigen Prostate Stem Cell Antigen Early Prostate Cancer Antigen B7-H3 Sarcosine Caveolin-1 Serum Calcium Hypermethylation of PDZ, LIM Domain Protein 4 Gene, and PDLIM5 Exosomes Ki-67 Golgi Phosphoprotein 2 and 3 DAB2 Interacting Protein Other Emerging Prostate Cancer Biomarkers Concluding Remarks and Future Directions References Part VIII: Disease Biomarkers 49. Biomarkers of Alzheimer's Disease Introduction Genetic Risk Factors for Alzheimer's Disease Mechanisms of Synaptic Dysfunction and Neuronal Loss Long-Term Potentiation Impairments and Excitotoxicity Through Glutamatergic Dysfunction Posttranslational Modifications of Tau Cause Aggregation and Synaptic Starving Biomarkers Prognostic Biomarkers Decreased Cerebrospinal Fluid Aβ42 Increased Positron Emission Tomography Amyloid Imaging Elevated Cerebrospinal Fluid Total-Tau and Phospho-Tau Elevated Cerebrospinal Fluid p-tau:Aβ42 Ratio MicroRNA Biomarkers Diagnostic Biomarkers Brain Atrophy 18F-2-Deoxy-2-Fluoro-d-Glucose Positron Emission Tomography Single-Photon Emission Computed Tomography Perfusion Imaging F2-Isoprostanes Concluding Remarks and Future Directions References 50. Biomarkers of Parkinson's Disease Abbreviations Introduction Genetic Biomarkers α-Synuclein LRRK2 Parkin PINK1 DJ-1 Biochemical Markers α-Synuclein and Abnormal Protein Accumulations Mitochondrial Dysfunction and Oxidative Stress Markers DJ-1 Urate 8-OHG and 8-OHdG Neuroinflammation Markers Apoptosis Markers Neuroimaging Markers Concluding Remarks and Future Directions Acknowledgments References 51. Biomarkers for Drugs of Abuse and Neuropsychiatric Disorders: Models and Mechanisms Introduction Drugs of Abuse Neuronal Basis of Drug Dependence Neurotoxicity of Psychostimulants Amphetamine Oxidative Stress Due to High Dopamine Content in Methamphetamine-Induced Neurotoxicity Fos B Transcription Factor Is Responsible for the Synaptic Modification Following Meth Abuse Meth Neurotoxicity Involving DNA Damage Meth Excitotoxicity Is Mediated by Glutamate Release and Activation of Glutamate Receptors Meth Neurotoxicity Is the Result of Blood–Brain Barrier Dysfunction and Hyperthermia Mitochondrial and Endoplasmic Reticulum–Dependent Death Pathway in Meth-Induced Apoptosis Neuroinflammatory Mechanism in Meth-Induced Neurotoxicity Cocaine Epigenetic Regulation (ΔFos-B and Cyclic Adenosine Monophosphate Response Element Binding Protein) in Cocaine-Induced Neuro ... Cocaine-Induced Changes in Synaptic Plasticity Is Mediated Through Brain-Derived Neurotrophic Factor Opioids Opioid Actions Are Orchestrated Through Inhibitory G Protein (Gi/Go) Intracellular Targets of Opioid Activation: cAMP, Ca2+, MAPK, CREB, AP-1 Transcription Factors Neurotoxic Effects of Opioids Linked with Oxidative Stress, Mitochondrial Dysfunction, and Apoptosis Cognitive Deficits During Opioid Addiction Are Due to Inhibition of Neurogenesis Cannabinoids/Marijuana Cannabinoid Signaling Is Mediated by Cannabinoid Receptors and Endocannabinoids Endogenous Cannabinoid Ligand Interaction With Cannabinoid Type 1 Receptor Regulates Expression of Genes Involved in Long-T ... Alcohol Modulation of γ-Aminobutyric Acid Type A and N-Methyl-d-aspartate Receptors by Ethanol Contributes to Anxiety, Arousal, and ... Astrocytes Are the Main Site of Ethanol-Induced Oxidative Stress and Neurotoxicity Generation of Proinflammatory Molecules Activates Mitogen-Activated Protein Kinase Signaling by Ethanol Abused Substances and Neuropsychiatric Disorders Schizophrenia Bipolar Disorder/Mood Disorder Anxiety Disorders Animal Models in Neuropsychiatry Animal Models of Depression Animal Models of Anxiety Animal Models of Schizophrenia Biomarkers of Bipolar Disorder and Schizophrenia Biomarkers of Schizophrenia Concluding Remarks and Future Directions References 52. Osteoarthritis Biomarkers Abbreviations INTRODUCTION PATHOPHYSIOLOGY AND SIGNALING PATHWAYS IN OSTEOARTHRITIS CLASSIFICATION OF OSTEOARTHRITIS BIOMARKERS BIOMARKERS OF COMFORT, MOBILITY, FUNCTION, AND INFLAMMATION AND PAIN Humans Animals Observation of Ortolani and Cranial Tibial Drawer Examination OSTEOARTHRITIS BIOMARKERS IN SERUM, SYNOVIAL FLUID, AND URINE Biomarkers of Inflammation Cytokines/Adipocytokines, Chemokines, and Neuropeptides Prostaglandin E2 and EP4 Receptor Fractalkine Erythrocyte Sedimentation Rate Biomarkers of Osteoarthritis Progression and Cartilage Degeneration Cartilage Oligomeric Matrix Protein (COMP) Matrix Metalloproteinases (MMPs) Hyaluronan Lubricin Follistatin-Like Protein 1 (FSTL 1) Ghrelin TSG-6 Cartilage Damage and Imaging Biomarkers Newly Identified Biomarkers DNA-Methylation and MicroRNAs (miR) CORRELATION OF CIRCULATORY BIOMARKERS WITH RADIOGRAPHIC/IMAGING BIOMARKERS AND SYMPTOMS OF OSTEOARTHRITIS CONCLUDING REMARKS AND FUTURE DIRECTIONS Acknowledgments References 53. Pathological Biomarkers in Toxicology Introduction Diagnostic Pathology Enzootic Hematuria Cyclopia Taxus (Yew) Poisoning Ergotism Morphologic (Gross and Microscopic) and Clinical Pathology Solar Injuries Skin Photosensitization Skin Neoplasia Iatrogenic Acromegaly in Dogs Endocrine Alopecia Alopecia and Inhibition of Hair Growth (Mimosine Toxicity) Acute Bovine Pulmonary Edema and Emphysema Toxic Myopathy—Ionophore Toxic Syndrome Drug-Eluting Stents Hepatopathies Glycogen Hepatopathy Hepatotoxicity Secondary to Enzyme Induction Peroxisome Proliferator-Activated Receptor Hepatopathy (Characteristic Lesion by Light and Electron Microscopy) in Rodents Iron Toxicosis Copper Poisoning in Sheep Nephropathies Polycystic Kidney Disease in Rats Alpha 2-Microglobulin Nephropathy Tubulointerstitial Nephritis Ethylene Glycol (Oxalate) Poisoning Melamine Poisoning Lead Toxicity Nephrotoxicity and Acute Renal Injury Polioencephalomalacia Sodium Chloride Toxicity Nigropallidal Encephalomalacia in Horses Phospholipidosis Concluding Remarks and Future Directions References 54. Oral Pathology Biomarkers Introduction Anatomical and Histological Considerations of the Oral Cavity Teeth Histology of Oral Mucosa Oral Physiology and Pharmacodynamics Biomarkers in the Oral Cavity Common Drugs and Toxicants showing Oral Manifestations Select Diseases of the Oral Cavity Oral Biomarkers of Exposure and Effects of Select Drugs/Toxicants Tetracycline/Minocycline Mercury and Silver Lead Biomarkers of Select Diseases Periodontal Disease Immunologically Mediated Oral Diseases Pemphigus Pemphigoid Oral Lichen Planus Oral Squamous Cell Carcinoma Saliva: A Hidden Plethora of Biomarkers Concluding Remarks and Future Directions References Part IX: Special Topics 55. Biomarkers of Mitochondrial Dysfunction and Toxicity Introduction Mitochondrial Function: General Overview Mitochondrial Toxicity Xenobiotics and Mitochondrial Dysfunction Mitochondria and Disease Mitochondrial Dysfunction in Diabetes Mitochondrial Dysfunction in Ischemia/Reperfusion Mitochondrial Dysfunction in Cancer Concluding Remarks and Future Directions References 56. Biomarkers of Blood–Brain Barrier Dysfunction Introduction Structure and Function of Brain Barriers In Vivo and In Vitro Models to Study the Blood–Brain Barrier In Vivo Model In Vitro Models Toxicants Affecting the Central Nervous System Barriers Metals Aluminum Copper and Iron Lead Manganese Mercury Zinc Pesticides Organophosphates Organochlorines and Pyrethrins/Pyrethroids Rotenone Herbicides Mycotoxins Drugs of Abuse and Therapeutic Drugs Methamphetamine Cocaine Alcohol/Ethanol Neurodegenerative Diseases and Other Conditions Neurodegenerative Diseases Epilepsy HIV Infection Concluding Remarks and Future Directions Acknowledgments References 57. Biomarkers of Oxidative/Nitrosative Stress and Neurotoxicity Introduction Lipid Peroxidation and Markers of Oxidative Stress Prostaglandin-Like Compounds as In Vivo Markers of Oxidative Stress Aldehydes as Lipid Peroxidation Products Reactivity of Lipid Peroxidation Products Excitotoxicity and Oxidative Damage Neuroinflammation and Oxidative Injury Metal Toxicity and Oxidative Injury Manganese Mercury Concluding Remarks and Future Directions References 58. Cytoskeletal Disruption as a Biomarker of Developmental Neurotoxicity Introduction Microtubules Effects of Organophosphorus Esters on Microtubules Effects of Heavy Metals on Microtubules Effects of Organic Solvents and Polybrominated Diphenyl Ethers on Microtubules Microfilaments Effects of Organophosphorus Esters on Microfilaments Effects of Heavy Metals on Microfilaments Effects of Organic Solvents and Polybrominated Diphenyl Ethers on Microfilaments Intermediate Filaments Effects of Organophosphorus Esters on Intermediate Filaments Effects of Heavy Metals on Intermediate Filaments Effects of Organic Solvents and Polybrominated Diphenyl Ethers on Intermediate Filaments Concluding Remarks and Future Directions References 59. MicroRNA Expression as an Indicator of Tissue Toxicity and a Biomarker in Disease and Drug-Induced Toxicological Evaluation Introduction Regulatory Mechanisms of miRNA Biogenesis Standard Toxicity Measurements (Tissue and Circulating Biomarkers) Toxicology Clinical Pathology Overview Hematology Clinical Chemistry Urinalysis Coagulation Tests Anatomic Pathology Nomenclature Database Sample Preparation Kinetics and Pharmacokinetics/Pharmacodynamics MiRNA Biomarkers of Toxicity in Organ Systems Esophagus miRNAs as Biomarkers of Pancreatic Toxicity Liver Heart Kidney Brain Environmental Exposure and miRNA Role of miRNA in Arsenic-Induced Carcinogenesis Concluding Remarks and Future Directions References 60. Citrulline: Pharmacological Perspectives and Role as a Biomarker in Diseases and Toxicities List of Abbreviations Introduction Citrulline or Arginine Supplementation Salient Aspects of Nitric Oxide Biochemical Aspects Pharmacokinetics and Pharmacodynamics of Citrulline Pharmacodynamics of Citrulline Citrulline in Sickle Cell Anemia Citrulline and Cardiovascular Effects Citrulline in Hypertension Citrulline in Diabetes Citrulline as Immunomodulator Citrulline Therapy May Decrease Severity of Sepsis Citrulline in Arginase-Associated T-Cell Dysfunction Citrulline: Role in Dementia of Alzheimer's Disease and in Multi-Infarct Dementia Citrulline: Can It Improve Aerobic Function/Energy Production? Citrulline for Urea Cycle Disorders Citrulline for Acceleration of Wound Healing Citrulline in Intestinal Pathology Citrulline: Effects of Amino Acids on Hair Strength Citrulline's Effect on Protein Synthesis Citrulline as a Biomarker in Diseases Citrulline as a Biomarker in Intestinal Disease Citrulline as a Biomarker in Celiac Disease Citrulline: Is It a Reliable Biomarker in Critically Ill Patients? Citrulline as a Biomarker to Identify Patients at High Risk of Developing a Catheter-Related Bloodstream Infection Citrulline as a Biomarker for Gastrointestinal Tolerance to Enteral Feeding Anticyclic Citrullinated Peptide Antibodies: A Novel Biomarker of Rheumatoid Arthritis Citrulline as a Biomarker in Periodontitis for Presymptomatic Rheumatoid Arthritis? Citrulline as a Biomarker in Rheumatoid Arthritis in Patients With Active Tuberculosis Conditions in Which Citrulline May Prove to Be a Biomarker in the Future Conditions Detected by Anticyclic Citrullinated Peptide Citrulline as a Biomarker for Brucellosis Presenting With Peripheral Arthritis Citrulline as a Biomarker for Sjögren's Syndrome Conditions Detected by Citrulline Levels Citrulline as a Biomarker in Transplants Citrulline as a Biomarker in Acute Respiratory Distress Syndrome Citrulline as a Biomarker in Polycystic Ovary Syndrome Citrulline as a Biomarker in Acute Kidney Injury Homocitrulline as a Biomarker for Renal Failure Citrulline as a Biomarker in Critically Ill Patients and Correlation With Severity of Inflammation Citrulline as a Biomarker in Intrauterine Growth Retardation Citrulline as a Biomarker of Congenital Anomalies Citrulline as a Biomarker for OAT Deficiency in Early Infancy Citrulline as a Biomarker in Citrin Deficiency Citrulline as a Biomarker in Toxicities Citrulline as a Biomarker of Kainic Acid–Induced Neurotoxicity Citrulline as a Biomarker of Anticholinesterase Poisoning Citrulline as a Biomarker of Ammonia Toxicity? Concluding Remarks and Future Directions References Part X: Applications of Biomarkers in Toxicology 61. Analysis of Toxin- and Toxicant-Induced Biomarker Signatures Using Microarrays Biomarkers and Biomarker Signatures in Disease: a Variety of Marker Classes and Possible Inferences Selecting Sample Sources for the Measurement of Biomarkers Individual Biomarkers and Aggregated Biomarker Signatures Approaches to Biomarker Signature Characterization Multiplexed High Content Solid Phase Immunoassays Flow Cytometry and Fluorescence-Activated Cell Sorting Immunohistochemistry and Tissue Microarrays Mass Spectrometry Analysis Grating-coupled Surface Plasmon Resonance Microarray Analysis Biomarker Signatures in the -Omics era Genomic and Transcriptomic Analyses Proteomics Metabolomics Lipidomics Genotype–Phenotype Associations Data Analysis Considerations Concluding Remarks and Future Directions Acknowledgments Conflict of Interest Declaration References 62. Biomarkers Detection for Toxicity Testing Using Metabolomics Introduction to Metabolomics Metabolomics Experimental Overview Study Design and Planning Sample Collection and Quenching Sample Preparation Instrumental Analysis Raw Data Processing Statistical Analysis of Processed Data Identification of Putative Biomarkers Biomarker Validation Metabolomics Experimental Overview Conclusions Applications of Metabolomics Biomarkers in Toxicity Testing Metabolomics in Toxicology Consortia Metabolomics Biomarkers in Hepatotoxicity Metabolomics Biomarkers in Renal Toxicity Metabolomics Biomarkers of Toxicity From Chemical Agents Metabolomics Biomarkers in Neurotoxicity Metabolomics Biomarkers of Biotoxins Metabolomics Biomarkers of Nanomaterials Metabolomics Biomarkers of Drugs of Abuse Concluding Remarks and Future Directions References 63. Transcriptomic Biomarkers in Safety and Risk Assessment of Chemicals Introduction Transcriptomics Transcriptomic Methods Types of Transcriptomic Biomarkers Transcriptomics in Biomarker Discovery Cardiovascular Biomarkers Hepatic Biomarkers Biomarkers of Anabolic Agents Infectious Agents and Sepsis Tobacco and Risk Continuum Environmental Chemical Risk Assessment Concluding Remarks and Future Directions References 64. Percellome Toxicogenomics Project as a Source of Biomarkers of Chemical Toxicity Introduction Materials and methods for Percellome Data Generation and example studies Experimental animals and dose setting Microarray data generation Comprehensive Selection of Responding mRNAs Estragole Study Pentachlorophenol Study Merging of TGP Data to Percellome Database New Repeated Dosing Study Results and Discussion Estragole Study PCP Study Merging the TGP Data to Percellome Database New Repeated Dosing Study Concluding Remarks and Future Directions Acknowledgments References 65. Proteomics in Biomarkers of Chemical Toxicity Introduction Heavy Metals Arsenic Cadmium Chromium (VI) Lead Mercury Pesticides and Herbicides Methyl Parathion Diazinon Paraquat Glyphosate Organic Pollutants Benzo(a)pyrene 2,3,7,8-Tetrachlorodibenzo-p-Dioxin Concluding Remarks and Future Directions References 66. Biomarkers for Testing Toxicity and Monitoring Exposure to Xenobiotics Introduction Requirements Expected in a Biomarker for Toxicology Testing and Biomonitoring Xenobiotics Exposure Biological Samples Used for Biomonitoring Exposure Through Biomarkers Biomarkers of Exposure for Monitoring Xenobiotics Exposure Adducts: A Relevant Case of Biomarkers of Exposure Biomarkers of Effect for Toxicology Testing Molecular Biomarkers for In Vitro Testing Toxicity Concluding Remarks and Future Directions References 67. Biomarkers in Epidemiology, Risk Assessment and Regulatory Toxicology Introduction Biomarkers New Advances in Biomonitoring, Exposure Science, Toxicology, Risk Assessment, and Decision-Making Biomarkers of Exposure Methylmercury Biomarkers of Effect Cholinesterase Inhibition Selenium Biomarkers of Susceptibility Cancer-Related Biomarkers Formaldehyde Concluding Remarks and Future Directions References Index A B C D E F G H I J K L M N O P Q R S T U V W X Y Z Back Cover
