High Altitude Sickness – Solutions from Genomics, Proteomics and Antioxidant Interventions

Preface
About the Book
Contents
About the Editors
1: Introduction to High Altitude and Hypoxia
	1.1 Introduction
	1.2 High Altitude and Oxygen Availability
	1.3 Acclimatization at High Altitude
		1.3.1 Acute Mountain Sickness
		1.3.2 High Altitude Cerebral Oedema (HACE)
			1.3.2.1 Intracellular Oedema
			1.3.2.2 Ionic Oedema
			1.3.2.3 Vasogenic Oedema
		1.3.3 High Altitude Pulmonary Oedema (HAPE)
	1.4 Hypobaric Hypoxia and Brain
		1.4.1 Brain as a Vulnerable Site of Oxidative Stress
		1.4.2 Hypobaric Hypoxia and Memory Functions
	1.5 Other Neurological Effects at High Altitude
	References
2: High Altitude Sickness: Environmental Stressor and Altered Physiological Response
	2.1 Introduction
		2.1.1 High Altitudes
		2.1.2 Environment at High Altitudes and Defining ``Hypoxia´´
			2.1.2.1 Identifying the Concept of ``Hypoxia´´
			2.1.2.2 Types of Hypoxia
			2.1.2.3 Symptoms of High Altitude Hypoxia
		2.1.3 Ultraviolet Radiation
		2.1.4 Cold
	2.2 Physiological Changes at High Altitude
		2.2.1 Acclimatization to High Altitude
			2.2.1.1 Pulmonary Ventilation or Hyperventilation
			2.2.1.2 Polycythaemia
		2.2.2 Affinity of Haemoglobin for Oxygen at Sea Level and At High Altitudes
		2.2.3 High Altitude and Oxidative Stress
	2.3 Conclusion
	References
3: High Altitude Related Diseases: Milder Effects, HACE, HAPE, and Effect on Various Organ Systems
	3.1 Introduction
	3.2 Epidemiology of High Altitude Sickness
	3.3 Mechanisms of High Altitude Sickness
	3.4 Milder Effects of High Altitude (AMS)
	3.5 High Altitude Pulmonary Oedema (HAPE)
	3.6 High Altitude Cerebral Oedema (HACE)
	3.7 High Altitude Related Cardiac Perturbations
	3.8 High Altitude Related Perturbations in Muscles
	3.9 High Altitude Related Perturbations in Kidney
	3.10 High Altitude Related Perturbations in Liver
	3.11 Conclusion
	References
4: High Altitude-Induced Oxidative Stress, Rheumatoid Arthritis, and Proteomic Alteration
	4.1 Oxidative Stress
		4.1.1 Oxidants
			4.1.1.1 Endogenous Source
			4.1.1.2 Exogenous Source
		4.1.2 Antioxidants
	4.2 High Altitude Mediated Oxidative Stress
		4.2.1 High Altitude and Oxidative Damage
		4.2.2 RONS Generation at High Altitude
		4.2.3 Hypoxia and Oxidative Stress
	4.3 Rheumatoid Arthritis (RA)
		4.3.1 Oxidative Stress in RA
		4.3.2 High Altitude and RA
		4.3.3 Reactive Species Measurement in RA
	4.4 Oxidative Stress Measurement
	4.5 High Altitude and Proteomic Alteration
	4.6 Conclusion
	References
5: Oxidative Stress, ROS Generation, and Associated Molecular Alterations in High Altitude Hypoxia
	5.1 Introduction
	5.2 Mechanisms of Oxidant Generation
		5.2.1 Oxidants Generation in Mitochondria
		5.2.2 Oxidant Generation in Phagocytic and Non-phagocytic Cells
	5.3 Defence Mechanism Against Oxidative Stress
		5.3.1 Enzymatic Antioxidants
		5.3.2 Non-Enzymatic Antioxidants
	5.4 Organ-Level Oxidative Damage Manifested by Cellular ROS
		5.4.1 Oxidative Damage in Lungs
		5.4.2 Oxidative Damage in Brain
		5.4.3 Oxidative Damage in Heart
	5.5 Oxidative Perturbations Mediated Changes in Proteome
	5.6 Conclusion
	References
6: High Altitude Induced Thrombosis: Challenges and Recent Advancements in Pathogenesis and Management
	6.1 Introduction
	6.2 Genetic Risk Factors for VTE
		6.2.1 Factor V Leiden
		6.2.2 Deficiency of Protein C, Protein S and Antithrombin
		6.2.3 Prothrombin Mutation
	6.3 Acquired Risk Factors for VTE
		6.3.1 Surgery/Trauma
		6.3.2 Advanced Age
		6.3.3 Cancer
		6.3.4 Oral Contraceptives and Hormone Replacement Therapy
		6.3.5 Immobilization
	6.4 Modern Lifestyle Risk Factors for VTE
		6.4.1 Virchow´s Triad
	6.5 Hypoxia at High Altitude
	6.6 High Altitude Thrombo-Embolism (HATE)
	6.7 Pathogenesis of HATE
		6.7.1 Ascent to an Elevated Region
		6.7.2 Long Haul Air Travel
		6.7.3 Simulated Hypobaric Hypoxia
	6.8 Evidence from Pre-Clinical Studies
	6.9 Clinical Management of HATE
	6.10 Conclusion
	References
7: Current Problems in Diagnosis and Treatment of High-Altitude Sickness
	7.1 Introduction
	7.2 Acute Mountain Sickness (AMS)
	7.3 High-Altitude Cerebral Edema
	7.4 High-Altitude Pulmonary Oedema (HAPE)
	7.5 Prevention Strategies for Acute Mountain Sickness (AMS) and High-Altitude Cerebral Edema (HACE)
		7.5.1 Non-Pharmacological Strategies
		7.5.2 Other Strategies
		7.5.3 Pharmacological Strategies
	7.6 Treatment of HAI
		7.6.1 Treatment of Acute Mountain Sickness
		7.6.2 Treatment of High-Altitude Cerebral Edema
		7.6.3 Treatment of High-Altitude Pulmonary Edema
	7.7 Better Prophylactics and Therapeutics
	References
8: Proteomics as a Potential Tool for Biomarker Discovery
	8.1 Introduction
	8.2 How Proteomics Is Useful?
		8.2.1 History of Proteomics
		8.2.2 Overview of Proteomics
		8.2.3 Types of Proteomics
			8.2.3.1 Protein Expression Proteomics
			8.2.3.2 Structural Proteomics
			8.2.3.3 Functional Proteomics
			8.2.3.4 Clinical Proteomics
		8.2.4 Proteomics as a Platform to Discover Potent Biomarker
	8.3 Common Proteomic Approaches
		8.3.1 Two-Dimensional Gel Electrophoresis (2DGE)
		8.3.2 Two-Dimensional Difference Gel Electrophoresis (2D-DIGE)
		8.3.3 Mass Spectrometry (MS)
			8.3.3.1 MALDI-TOF MS
			8.3.3.2 ESI MS/MS
			8.3.3.3 Surface-Enhanced Laser Desorption Ionization (SELDI)
			8.3.3.4 ``Short-Gun´´ Approach
		8.3.4 Isotope-Coded Affinity Tag (ICAT)
		8.3.5 Isobaric Tag for Relative and Absolute Quantitation (iTRAQ)
	8.4 Biomarker and Disease
		8.4.1 Autoimmune Disease
			8.4.1.1 Rheumatoid Arthritis (RA)
			8.4.1.2 Systemic Lupus Erythematosus (SLE)
			8.4.1.3 Type 1 Diabetes (Diabetes Mellitus)
			8.4.1.4 Multiple Sclerosis
	8.5 Conclusion
	References
9: Serum and Plasma Proteomics for High Altitude Related Biomarker Discovery
	9.1 Introduction
	9.2 Plasma and Serum and Their Potentials in the Diagnosis
	9.3 Proteomics Approaches to Study Plasma and Serum
		9.3.1 Immunoblotting
		9.3.2 2D Gel Electrophoresis and Mass Spectrometry
		9.3.3 Non-gel Based Quantitative Proteomics
	9.4 Key Considerations for Biomarker Discovery for High Altitude Physiology
	9.5 Potentials Biomarker Candidates in High Altitude Pathophysiology
		9.5.1 Antioxidant Signaling
		9.5.2 Lipid Metabolism
		9.5.3 Cytoskeleton Remodeling
		9.5.4 Post-Translational Modifications
	9.6 Future Prospects and Conclusion
	References
10: Saliva Proteomics as Non-Invasive Application for Biomarker Studies
	10.1 Saliva: A Novel Informative Sample
	10.2 Hypobaric Hypoxia: A Pathophysiological Condition
	10.3 Redox Stress: Molecular Responses in Hypobaric Hypoxia
	10.4 Use of Biological Fluids Such as Plasma/Serum in Search of Potential Protein Markers
	10.5 Saliva as a Diagnostic Fluid in Translational Studies
	10.6 Saliva in Response to Hypobaric Hypoxia
	10.7 Proteins Evolved as Biomarkers for Hypobaric Hypoxia
		10.7.1 Alpha-Enolase
		10.7.2 Cystatins
		10.7.3 Apoptosis Inducing Factor 2 (AIF2)
		10.7.4 Prolactin Inducible Protein (PIP)
		10.7.5 Carbonic Anhydrase 6 (CA6)
		10.7.6 Phospholipid Transfer Protein (PLTP)
		10.7.7 Interleukin 1 Receptor Antagonist (IL1R1)
		10.7.8 Albumin, Alpha-1 Acid Glycoprotein, and Alpha-1 Antitrypsin
	10.8 Concluding Remarks
	References
11: Role of Genomics, Proteomics, and Antioxidant Interventions in Preventing High Altitude Sickness
	11.1 Introduction
		11.1.1 Role of Genetic Factors Towards High Altitude Sickness
		11.1.2 Role of Proteomics Towards High Altitude Sickness
		11.1.3 Role of Antioxidants Towards High Altitude Sickness
	11.2 Conclusion
	References
12: High Altitude Sickness and Antioxidant Interventions
	12.1 Introduction
	12.2 Acute Mountain Sickness (AMS), High Altitude Cerebral Edema (HACE), and High Altitude Pulmonary Edema (HAPE)
	12.3 Diverse Strategies for Preventing High Altitude Sickness (HAS)
		12.3.1 Pharmacological Interventions
		12.3.2 Non-Pharmacological and Miscellaneous Interventions
	12.4 Cellular Antioxidant System and its Alteration in Relation to HAS
	12.5 Role of Antioxidant Interventions and Prophylactic Benefits in HAS
	References
13: Antioxidant Therapy for High Altitude Sickness and Nano-Medicine
	13.1 Introduction
	13.2 From Physiological to Molecular: Change of Perspectives
	13.3 Stabilization of HIF in Signaling of ROS During Hypoxic Conditions
	13.4 Association of PGC-1 α and Sirtuins with HIF-1α in Signaling of ROS
	13.5 Nuclear Erythroid-Related Factor 2
	13.6 Oxidative Stress Markers at High Altitude
	13.7 Physiological Consequences of Oxide Generated Stress
	13.8 Antioxidant Therapy for High Altitude Sickness
	13.9 Effects on Antioxidant System at High Altitude
	13.10 Status of Antioxidant Defense System in Body
	13.11 Antioxidant Therapy: Prevention of High Altitude Sickness
	13.12 Nano-Medicine in Acute Mountain Sickness
		13.12.1 Beginning of Nanotechnology
		13.12.2 Nano-Formulations
		13.12.3 Hypoxic Nano-Formulations
		13.12.4 Hypobaric Hypoxia and Nano-Formulations
		13.12.5 Nano-Curcumin for Hypobaric Hypoxia
		13.12.6 Nanoceria for Hypobaric Hypoxia
		13.12.7 Nano-Formulations Forthcoming for Hypobaric Hypoxia
	13.13 Conclusion
	References