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E-grāmata: Vitamin D: Volume 2: Health, Disease and Therapeutics

Edited by (Harvard TH Chan School of), Edited by (Professor in Endocrinology, University and University Hospital, Catholic University of Leuven (K.U.Leuven), Belgium), Edited by (Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK), Edited by
  • Formāts: EPUB+DRM
  • Izdošanas datums: 14-Dec-2017
  • Izdevniecība: Academic Press Inc
  • Valoda: eng
  • ISBN-13: 9780128099643
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  • Formāts: EPUB+DRM
  • Izdošanas datums: 14-Dec-2017
  • Izdevniecība: Academic Press Inc
  • Valoda: eng
  • ISBN-13: 9780128099643
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Vitamin D: Volume 2: Health, Disease and Therapeutics, Fourth Edition, authoritatively covers the evidence for new roles for vitamin D, ranging from cardiovascular disease, to cancer, diabetes, inflammatory bowel disease, multiple sclerosis and renal disease.

This collection represents a who’s who of vitamin D research and the coverage is appropriately broad, drawing in internal medicine, orthopedics, oncology and immunology. Clinical researchers will gain a strong understanding of the molecular basis for a particular area of focus.

  • Offers a comprehensive reference, ranging from basic bone biology, to biochemistry, to the clinical diagnostic and management implications of vitamin D
  • Saves researchers and clinicians time in quickly accessing the very latest details on the diverse scientific and clinical aspects of Vitamin D, as opposed to searching through thousands of journal articles
  • Chapter authors include the most prominent and well-published names in the field
  • Targets chemistry, metabolism and circulation, mechanisms of action, mineral and bone homeostasis and vitamin D deficiency
  • Presents a clinical focus on disorders, analogs, cancer, immunity, inflammation, disease and therapeutic applications

Papildus informācija

Comprehensive translational reference, focusing on the therapeutic applications of vitamin D research and its relation to a variety of diseases
VOLUME II
VII POPULATION STUDIES: VITAMIN D DEFICIENCY, NUTRITION, SUNLIGHT, GENES & TRIALS
58 Methods of Evaluating Population Studies of Vitamin D: Strengths and Weaknesses
Edward Giovannucci
Introduction
3(1)
Methods of Assessing Vitamin D Status
4(3)
Main Challenges in the Epidemiologic Study of Vitamin D and Disease
7(2)
Summary of Study Designs of Vitamin D
9(3)
Conclusions
12(1)
References
13(2)
59 Worldwide Vitamin D Status
Natasja Van Schoor
Paul Lips
Introduction
15(1)
Vitamin D Status in North America (Including Canada and Mexico)
16(5)
Vitamin D Status in South America
21(1)
Vitamin D Status in Europe
21(1)
Vitamin D Status in Middle East
21(1)
Vitamin D Status in Asia
21(1)
Vitamin D Status in Africa
21(5)
Vitamin D Status in Oceania
26(1)
Multicenter and Global Studies Using a Central Laboratory Facility
26(8)
Ethnicity/Migration
34(1)
Nutrition
34(1)
Risk Groups
34(1)
Implications
34(1)
Conclusions
35(1)
References
35(6)
60 Vitamin D in Foods: An Evolution of Knowledge
Janet M. Roseland
Katherine M. Phillips
Kristine Y. Patterson
Pamela R. Pehrsson
Christine L. Taylor
Introduction
41(1)
Challenges in Assessing the Vitamin D Content of Foods
42(5)
Methods of Analysis for Vitamin D in Foods
47(7)
Food Composition Data
54(7)
Implications and Future Directions
61(1)
Appendix A
62(12)
References
74(5)
61 Determinants of Vitamin D Deficiency From Sun Exposure: A Global Perspective
William B. Grant
Harjit P. Bhattoa
Pawel Pludowski
Background
79(1)
Factors Affecting 25-Hydroxyvitamin D Concentrations
80(6)
Predicting Vitamin D Deficiency
86(1)
Conclusion
86(1)
References
86(5)
62 Vitamin D Fortification and Supplementation Policies to Correct Vitamin D Insufficiency/Deficiency Globally
Susan J. Whiting
Mona S. Calvo
Introduction
91(3)
Recommendations for Vitamin D Status
94(5)
Strategies to Improve Nutrient Intakes
99(5)
Public Health Measures for Reducing D Deficiency
104(2)
Summary
106(1)
References
106(3)
63 Vitamin D and Food Fortification
Kevin D. Cashman
Mairead Kiely
Introduction
109(3)
Current Intakes of Vitamin D in Young and Adult Populations in North America and Europe and How These Compare Against Dietary Targets?
112(1)
Dietary Strategies for Increasing Vitamin D Intake: Bridging the Gap By Food Fortification
112(8)
Consideration of Other Vitamin D-Fortified Foods
120(1)
Vitamin D-Biofortified Foods
121(2)
Safety Considerations and Prerequisite Data Required Prior to Initiating Public Health Measures
123(1)
Concluding Remarks
124(1)
References
125(4)
64 Bariatric Surgery, Vitamin D, and Bone Loss
Tiffany Y. Kim
Anne L. Schafer
Introduction
129(2)
Skeletal Effects of Bariatric Surgery
131(3)
Potential Mechanisms of Bone Loss
134(9)
Prevention and Treatment of Skeletal Effects
143(2)
Acknowledgments
145(1)
References
145(6)
65 Genetics of the Vitamin D Endocrine System
Andre G. Uitterlinden
Introduction
151(2)
Genetic Studies
153(4)
Genome-Wide Association Studies
157(5)
Future Developments
162(1)
Acknowledgments
162(1)
References
162(5)
66 Randomized Clinical Trials of Vitamin D for the Primary Prevention of Cancer and Cardiovascular Disease With a Focus on the VITamin D and OmegA-3 Trial (VITAL)
Shari S. Bassuk
Joann E. Manson
Introduction
167(1)
Vitamin D and Omega-3 Trial Study Design
168(2)
Baseline Characteristics of VITAL Participants
170(3)
Other Ongoing and Recently Completed Large and Midsized Trials of Vitamin D
173(1)
Conclusion
174(1)
Acknowledgments
174(1)
References
175(4)
VIII DISORDERS
67 Vitamin D Deficiency and Nutritional Rickets in Children
John M. Pettifor
Kebashni Thandrayen
Thomas D. Thacher
Introduction
179(1)
Historical Perspective
179(1)
The Epidemiology of Vitamin D Deficiency and Nutritional Rickets
180(2)
Clinical Presentation
182(2)
Biochemical Abnormalities
184(1)
Radiologic Changes
185(1)
The Growth Plate in Rickets
186(1)
Treatment and Prevention
187(3)
Dietary Calcium Deficiency
190(2)
The Pathogenetic Spectrum of Nutritional Rickets
192(1)
Conclusions
193(1)
References
194(10)
68 Vitamin D and Osteoporosis
Peter R. Ebeling
John A. Eisman
Effects of Vitamin D on the Skeleton
204(1)
The Role of Vitamin D Genetic Factors in Osteoporosis and Possible Interactions With Vitamin D Therapy
205(2)
Determining Optimal Serum 25 Hydroxyvitamin D Concentrations for Musculoskeletal Health
207(1)
Effects of Vitamin D Alone or Calcium and Vitamin D on Bone Mineral Density
207(2)
Primary Fracture Prevention With Vitamin D or Calcium and Vitamin D
209(1)
Effect of Vitamin D Alone on Fractures
209(1)
Single High Annual or Monthly Doses of Vitamin D
210(1)
Primary Fracture Prevention With Calcium and Vitamin D
211(1)
Metaanalyses
212(1)
Safety
213(1)
Secondary Fracture Prevention With Vitamin D or Calcium and Vitamin D
214(1)
Effects of Active Vitamin D Analogs on Fractures
215(1)
The Anabolic Vitamin D Analogs, 2MD
215(1)
The Vitamin D Analogs, Eldecalcitol
215(1)
Ongoing Large Randomized Controlled Trials of Vitamin D Supplementation
216(1)
Future Directions for Vitamin D in Osteoporosis
216(1)
References
216(5)
69 Adult Vitamin D Deficiency: Fracture and Fall Prevention
Bess Dawson-Hughes
Heike A. Bischoff-Ferrari
Vitamin D: Muscle and Balance
221(1)
Vitamin D and Falls
222(2)
Vitamin D: Bone Mineral Density and Fracture Risk
224(1)
Trials Testing Higher Doses of Vitamin D Given at Infrequent Intervals
225(1)
Conclusions
226(1)
References
226(3)
70 Clinical Disorders of Phosphate Homeostasis
Eva S. Liu
Harald Juppner
Phosphate Homeostasis
229(1)
Regulation of Phosphate Homeostasis
230(1)
Phosphate and Vitamin D Metabolism
231(1)
Clinical Symptoms of Hypophosphatemia and Hyperphosphatemia
231(1)
Disorders of Phosphate Homeostasis
232
Genetic Hypophosphatemic Disorders With Low Fibroblast Growth Factor
23(216)
Levels
239
Acquired Hypophosphatemic Disorders With Elevated Fibroblast Growth Factor
23(216)
Levels
239(1)
Genetic Hyperphosphosphatemic Disorders
240(1)
Disorders of Altered Phosphate Load
240(1)
References
241(8)
71 Vitamin D Hydroxylation--Deficient Rickets, Type 1A: CYP27B1 Mutations
Francis H. Glorieux
Rene St-Arnaud
Introduction
249(1)
Clinical Manifestations
250(1)
Biochemical Findings
251(1)
Genetic and Molecular Studies
252(3)
Treatment of VDDR1A
255(1)
Evolution of VDDR1A Under Treatment From Childhood to Adulthood
255(3)
Perspective and Conclusions
258(2)
References
260(4)
72 Hereditary 1,25-Dihydroxyvitamin D Resistant Rickets
Peter J. Malloy
Dov Tiosano
David Feldman
Introduction
264(1)
The Clinical Features of HVDRR
264(6)
Mechanism of 1,25(OH)2D Action
270(2)
Cellular Basis of HVDRR
272(6)
Molecular Basis for HVDRR
278(11)
Therapy of HVDRR
289(3)
Alopecia
292(1)
Concluding Remarks
293(1)
References
294(9)
73 The Role of Genetic Variation in CYP2R1, the Principal Vitamin D 25-Hydroxylase, in Vitamin D Homeostasis
Jeffrey D. Roizen
Michael A. Levine
Background
303(1)
CYP2R1 Is the Principal Human Vitamin D 25-Hydroxylase
304(3)
CYP2R1 and Vitamin D-Dependent Rickets
307(3)
In Vitro and In Silico Analyses of CYP2R1 Function
310(2)
Associations Between CYP2R1 Variants and Disease
312(1)
Conclusion and Future Directions
313(1)
References
313(4)
74 Infantile Hypercalcemia and CYP24A1 Mutations
Karl P. Schlingmann
Martin Konrad
Infantile Hypercalcemia---Differential Diagnosis
317(2)
Idiopathic Infantile Hypercalcemia---Historical Aspects
319(1)
Spectrum of Disease Caused By CYP24A1 Mutations
320(3)
Mutations In CVP24A1---Molecular Genetics
323(1)
Functional Studies of Mutant CYP24A1
324(1)
Measurement of CYP24A1 Activity In Vivo
324(1)
CYP24A1 Mouse Model
325(1)
Additional Defects Leading to an Increased Action of Vitamin D
325(1)
Therapeutic Aspects
326(1)
Summary and Conclusions
327(1)
References
328(3)
75 Drug and Hormone Effects on Vitamin D Metabolism
Gregory R. Emkey
Sol Epstein
Introduction
331(2)
Hormone Effects on Vitamin D Metabolism
333(9)
Drug Effects on Vitamin D Metabolism
342(12)
Conclusion
354(1)
References
354(21)
76 Vitamin D and Organ Transplantation
Jessica M. Furst
Emily M. Stein
Jessica Starr
Elizabeth Shane
Introduction
375(1)
Effects of Vitamin D on Immunity and Graft Rejection
375(1)
Vitamin D Deficiency Prior to Organ Transplant
376(1)
Vitamin D Deficiency Following Organ Transplant
377(1)
Treatment of Posttransplant Bone Loss With Vitamin D and Analogs
378(3)
Conclusions
381(1)
References
381
Further Reading
373(15)
77 The Role of Vitamin D in Type 2 Diabetes and Hypertension
Edith Angellotti
Anastassios G. Pittas
Epidemiology and Burden of Type 2 Diabetes and Hypertension
388(1)
Biologic Plausibility of an Association Between Vitamin D and Type 2 Diabetes and Hypertension
388(3)
Evidence From Human Studies for a Link Between Vitamin D and Type 2 Diabetes
391(15)
Evidence From Human Studies for a Link Between Vitamin D and Hypertension
406(4)
Summary of Evidence From Human Studies on Type 2 Diabetes and Hypertension and Limitations in the Study of Vitamin D
410(4)
Optimal Intake of Vitamin D in Relation to Type 2 Diabetes and Hypertension
414(1)
Conclusions
415(1)
References
415(10)
78 Vitamin D, Obesity, and the Metabolic Syndrome
Elina Hypponen
Barbara J. Boucher
Introduction
425(1)
Adipose Tissue as a Vitamin D Reserve
426(1)
Obesity and Vitamin D Deficiency
426(2)
Obesity, Vitamin D-Binding Proteins, and "Free" Vitamin D Concentrations
428(1)
The Effect of Weight Loss on Serum 25(OH)D Concentrations
429(1)
Can Vitamin D Supplementation Prevent, or Reduce, Obesity?
430(1)
Obesity and the Efficacy of Vitamin D Supplementation
431(2)
Brown Adipose Tissue, Obesity, and Vitamin D
433(1)
Obesity, Vitamin D, and Metabolic Syndrome
433(4)
Importance of Early Life D Status for Obesity and Subsequent Risks of Metabolic Syndrome, Type 2 Diabetes Mellitus, and Cardiovascular Disease
437(2)
Conclusions and Future Directions
439(1)
References
439(6)
79 Vitamin D and Renal Disease
Adriana S. Dusso
Jorge B. Cannata-Andia
Introduction
445(3)
Renal Maintenance of the Vitamin D Endocrine System
448(8)
Critical Calcitriol/VDR Actions to Improve Parathyroid, Skeletal, Renal, and Cardiovascular Outcomes in CKD
456(7)
Acknowledgments
463(1)
References
463(8)
80 Calcitriol and Analogs in the Treatment of Chronic Kidney Disease
Ishir Bhan
Ravi Thadhani
Introduction
471(1)
Analogs of Vitamin D Used in Chronic Kidney Disease
472(1)
Analogs in Animal Models of Uremia
472(3)
Chronic Kidney Disease Stages 3--4
475(2)
End-Stage Renal Disease
477(3)
Cardiovascular Disease in Chronic Kidney Disease and Different Forms of Vitamin D
480(1)
Conclusions
480(1)
References
481(4)
81 Idiopathic Hypercalciuria and Nephrolithiasis
Murray J. Favus
Meltem Zeytinoglu
Fredric L. Coe
Introduction to Kidney Stones
485(2)
Idiopathic Hypercalciuria
487(11)
Current View of Human Genetic Hypercalciuria
498(1)
Therapeutics of Idiopathic Hypercalciuria and Effects on Calcium Metabolism
498(2)
Genetic Hypercalciuric Rats
500(2)
Risk of Stone Formation Using Vitamin D Analogs
502(1)
References
502(3)
Further Reading
505(2)
82 Hypercalcemia Due to Vitamin D Toxicity
Natalie E. Cusano
Susan Thys-Jacobs
John P. Bilezikian
Introduction
507(1)
Forms of Exogenous Vitamin D Toxicity
508(3)
Forms of Endogenous Vitamin D Toxicity
511(6)
Clinical Manifestations
517(2)
Summary and Conclusions
519(1)
References
520(7)
83 The Hypocalcemic Disorders
Rachel I. Gafni
Karl L. Insogna
Thomas O. Carpenter
Physiology
527(3)
Clinical Manifestations of Hypocalcemia
530(1)
Differential Diagnosis of Hypocalcemia
530(8)
Treatment of Hypocalcemia
538(3)
Conclusion
541(1)
Acknowledgments
541(1)
References
541(8)
84 Vitamin D: Cardiovascular Effects and Vascular Calcification
Christoph Zechner
Dwight A. Towler
Introduction
549(1)
Vitamin D Signaling in Myocardial Remodeling and Function
550(2)
Vitamin D Actions in Atherosclerosis and Arteriosclerosis
552(2)
Vitamin D and Human Cardiovascular Disease: Compelling Epidemiology and Physiology, Emerging but Less Compelling Evidence of Interventional Benefit Still Persists
554(1)
Vitamin D Intoxication and Cardiovascular Calcification: Pharmacological Considerations
555(1)
The Impact of Calcium, Phosphate, and Vitamin D Excesses on Smooth Muscle Matrix Vesicle Physiology and Vascular -- Calcification
556(2)
The FGF23/Klotho/Vitamin D Axis, Nephrocalcinosis, and Cardiovascular Calcification
558(2)
Vitamin D, Vascular Parathyroid Hormone Receptor Signaling, and Arteriosclerotic Calcium Accrual: Lessons Learned From Preclinical Models and Patients With End-Stage Renal Disease
560(1)
Defining Cardiovascular Toxicity Thresholds for Vitamin D: Critical Clues From the Clinical Literature
561(1)
Vitamin D, the Calcium-Sensing Receptor, and Cardiovascular Disease
561(1)
Summary, Conclusions, and Future Directions
562(1)
Acknowledgments
563(1)
References
563(8)
85 Vitamin D and Paget's Disease
Noriyoshi Kurihara
G. David Roodman
Introduction
571(1)
Mechanism of Action of 1,25(OH)2D3 on Osteoclast Formation
572(1)
Increased Levels of TAF12 in Osteoclast Precursors From Paget's Disease Patients Contribute to Their Hyperresponsivity to 1,25(OH)2D3
572(1)
TAF12 Expression Is Increased in Osteoclasts From Patients With Paget's Disease
573(1)
Overexpression of TAF12 Is Sufficient to Induce 1,25(OH)2D3 Hyperresponsivity in Human Osteoclast Precursors
574(2)
Mechanism of Action of TAF12 in the Increased 1,25(OH)2D3 Responsivity of OCL Precursors From PD Patients
576(1)
Marrow Stromal Cells Derived From p62P394L Knock-In mice and p62P392L Paget's Patients Are Hyperresponsive to 1,25(OH)2D3 and Display Enhanced RANKL Production in Response to 1,25(OH)2D3
576(1)
Serum Concentrations of 1,25(OH)2D3 in Paget's Patients
577(1)
Conclusion
577(1)
References
578(5)
IX VITAMIN D ANALOGS
86 Analogs of Calcitriol
Lieve Verlinden
Roger Bouillon
Pierre Declercq
Annemieke Verstuyf
Introduction
583(1)
14-Epi Analogs of 1,25(OH)2D3
584(3)
Decalin Analogs
587(1)
C and D-Ring Analogs
588(12)
CF-Ring Analogs
600(1)
E-Ring Analogs
601(1)
Acyclic Analogs
601(1)
Nonsecosteroidal Compounds
601(8)
Gemini Analogs
609(2)
Conclusion
611(1)
References
611(4)
87 Nonsecosteroidal Ligands and Modulators of Vitamin D Receptor
Ryan E. Stites
James G. Mackrell
Keith R. Stayrcok
Introduction
615(1)
CD-Ring-Replacement Ligands
616(2)
Diarylmethane Ligands
618(3)
Miscellaneous Nonsecosteroids
621(2)
Nonsecosteroidal Modulators of Vitamin D Receptor-Coregulator Interactions
623(2)
Perspectives
625(1)
References
625(4)
88 Bile Acid-Derived Vitamin D Receptor Ligands
Makoto Makishima
Sachiko Yamada
The Vitamin D Receptor Is a Dual-Functional Receptor for Vitamin D and Bile Acids
629(2)
Bile Acids and Nuclear Receptors
631(4)
Development of Bile Acid Derivatives
635(2)
X-Ray Crystal Structures of Vitamin D Receptor in Complex With Lithocholic Acid and Its Derivatives
637(4)
Perspectives
641(1)
References
641(6)
89 Bifunctional Vitamin D Hybrid Molecules
James L. Gleason
John H. White
Introduction
647(1)
Combination Therapy and Bifunctional Agents
648(1)
Nuclear Receptor Ligands as Trojan Horses
649(1)
Vitamin D/Histone Deacetylase Inhibitor Hybrids
649(3)
Nonsecosteroidal Hybrids
652(1)
Non-HDACi Hybrids
652(1)
Conclusion
653(1)
References
653(4)
90 Modulating Vitamin D Receptor-Coregulator Binding With Small Molecules
Olivia B. Yu
Leggy A. Arnold
Introduction
657(1)
Vitamin D Receptor Coactivators
657(1)
Vitamin D Receptor Corepressors
658(1)
Inhibiting Vitamin D Receptor: VDR Antagonists Versus VDR--Coregulator Inhibitors
659(2)
Peptide-Based Inhibitors of Vitamin D Receptor-Coregulator Interactions
661(2)
Small Molecule-Based Inhibitors of Vitamin D Receptor-Coregulator Interactions
663(1)
Conclusion and Future Direction
664(1)
Acknowledgment
664(1)
References
664(3)
91 Extended-Release Calcifediol in Renal Disease
Martin Petkovich
Charles W. Bishop
Introduction
667(1)
Background---Vitamin D Signaling and Metabolism
668(2)
Treating Secondary Hyperparathyroidism Associated With Vitamin D Insufficiency in Chronic Kidney Disease
670(4)
Summary
674(1)
Acknowledgments
674(1)
References
674(5)
92 Vitamin D Receptor Antagonists
Hiroshi Saitoh
Introduction
679(1)
ZK Series
680(3)
Adamantyl Derivatives
683(1)
Lactam Derivatives
684(1)
Amide Derivative
685(1)
TEI-9647 and Its Derivatives
686(3)
22-Alkyl Derivatives
689(1)
Nonsecosteroidal Vitamin D Receptor Antagonist
690(1)
Conclusion and Directions for Future Study
691(1)
References
691(4)
93 Eldecalcitol and Osteoporosis
Toshio Matsumoto
Fumiaki Takahashi
Introduction
695(1)
Structure--Function Relationship
696(2)
Animal Studies
698(3)
Effect on Other Tissues
701(1)
Clinical Studies in Osteoporotic Patients
701(4)
Acknowledgments
705(1)
References
705(6)
X VITAMIN D AND CANCER
94 Overview of Vitamin D Actions in Cancer
Marjolein Van Driel
Johannes P.T.M. Van Leeuwen
Alberto Munoz
David Feldman
Introduction
711(1)
Vitamin D and Cancer
711(7)
Vitamin D Effects on Tumor Cells
718(6)
Combination Therapy
724(2)
Resistance and Vitamin D Metabolism
726(1)
Stimulation of Proliferation
727(1)
Conclusions
728(1)
References
728(15)
95 Vitamin D Status and Cancer Incidence, Mortality, and Prognosis
Irene Shui
Edward Giovannucci
Introduction
743(1)
Cancer Incidence
744(2)
Cancer Mortality and Survival
746(7)
References
753(9)
96 Effects of Vitamin D Derivatives on Differentiation, Cell Cycle, and Apoptosis in Hematological Malignancies
George P. Studzinski
Elzbieta Gocek
Frederick Coffman
Michael Danilenko
Differentiation of Myeloid Leukemia Cells by Vitamin D Derivatives
762(1)
Signaling and Execution of Monocytic Differentiation Induced by Vitamin D Derivatives
763(5)
Transcription Factors in Vitamin D Derivative-Induced Differentiation
768(1)
Role of Micro-RNAs in Hematopoiesis, Differentiation, and Cell Cycle Block
769(1)
Vitamin D Derivatives--Induced Progression of Monocytic to Macrophage Differentiation
770(1)
Effects of Vitamin D Derivatives on the Cell Cycle and Proliferation of Human Leukemia Cells
771(7)
Efects of Vitamin D Derivatives on Cell Survival and Cell Death
778(1)
Effects of Vitamin D Derivatives on Lymphoid Lineage Cells
779(1)
Clinical Applications of Vitamin D Derivatives' Actions Against Hematopoietic Malignancies
780(7)
Conclusions
787(1)
References
787(15)
97 Vitamin D Actions in Mammary Gland and Breast Cancer: Genomics, Metabolism, and Stem Cells
Sarah Beaudin
Joellen Welsh
Introduction to Breast Cancer
802(1)
Observational and Interventional Studies on Vitamin D and Breast Cancer
803(2)
Expression and Function of the Vitamin D Pathway in Normal and Neoplastic Breast Cells/Tissues
805(2)
Impact of Vitamin D Signaling in Animal Models of Breast Cancer
807(2)
Genomic Profiling of Vitamin D Receptor Agonists in Breast Cancer Model Systems
809(2)
New Mechanistic Insight Into Vitamin D Actions in Breast Cancer
811(3)
Overall Conclusions and Remaining Research Questions
814(1)
References
814(7)
98 The Antitumor Effects of Vitamin D in Genitourinary Cancer
Donald L. Trump
Introduction
821(1)
Prostate Cancer
822(6)
Bladder Cancer
828(1)
Renal Cell Carcinoma
829(1)
Summary
830(1)
References
831(5)
Further Reading
836(2)
99 Vitamin D and Colon Cancer
Antonio Barbachano
Maria Jesus Larriba
Gemma Ferrer-Mayorga
Jose Manuel Gonzalez-Sancho
Alberto Munoz
Introduction
838(3)
Human Studies
841(1)
Expression of Vitamin D Hydroxylases and the Vitamin D Receptor in Colon Cancer
842(2)
Mechanism of Action of 1,25(OH)2D3 in Colon Cancer
844(8)
Animal Models
852(3)
Conclusions
855(1)
References
855(8)
100 Vitamin D and Skin Cancer
Katherine J. Ransohoff
Ervin H. Epstein
Jean Y. Tang
Introduction
863(1)
Two Sources of Vitamin D: Diet or Sunlight
863(2)
Vitamin D and Indoor Tanning
865(1)
UV Exposure Contributes to the Development of Melanoma and Nonmelanoma Skin Cancer
866(1)
Vitamin D in Skin Cancer: Role of Vitamin D in Keratinocytes
867(1)
Role of Vitamin D in Squamous Cell Carcinomas
867(1)
Role of Vitamin D in Basal Cell Carcinomas
868(1)
Role of Vitamin D in Melanoma
869(1)
Photoprotection and Vitamin D Levels
870(1)
Conclusions
870(1)
References
870(6)
101 Vitamin D and Lung Cancer
Tatiana Shaurova
Mukund Seshadri
Pamela A. Hershberger
Lung Cancer Overview
876(1)
Etiology of Lung Cancer
876(1)
Vitamin D and Chronic Obstructive Pulmonary Disease
877(1)
Variation in Vitamin D Signaling Pathway Components and Lung Cancer Risk/Outcomes
878(1)
Vitamin D and the Chemoprevention of Nonsmall Cell Lung Cancer
879(1)
Vitamin D Actions in Nonsmall Cell Lung Cancer
880(4)
Vitamin D-Based Combination Therapies for Advanced Nonsmall Cell Lung Cancer: Preclinical Rationale and Clinical Studies
884(1)
Activity of Calcitriol Analogs in Nonsmall Cell Lung Cancer Models
884(1)
Conclusions
885(1)
Acknowledgments
885(1)
References
885(7)
102 Vitamin D Inflammation and Cancer
Eniko Kallay
Laura Buburuzan
Introduction
892(1)
Vitamin D and the Vitamin D System
893(1)
Inflammation
893(3)
Inflammation-Associated Cancer
896(8)
Conclusions
904(1)
References
904(11)
XI IMMUNITY, INFLAMMATION AND DISEASE
103 Vitamin D and Tuberculosis
Adrian R. Martineau
David A. Jolliffe
Julie Demaret
Introduction
915(1)
The Immune Response in Tuberculosis
916(1)
Influence of Vitamin D on the Immune Response to Mycobacterium tuberculosis
916(3)
Historical Studies
919(1)
Studies With Mycobacterium tuberculosis Infection as an End Point
920(1)
Studies With Active Tuberculosis Disease as End Point
921(6)
Studies of Treatment Outcome
927(2)
Conclusions
929(1)
References
929(9)
104 Vitamin D and Adaptive Immunology in Health and Disease
Elizabeth H. Mann
Paul E. Pfeffer
Catherine M. Hawrylowicz
Epidemiological Evidence for a Role of Vitamin D in Immune Disease
938(1)
Actions of Vitamin D on Proinflammatory T Lymphocyte Responses
938(1)
Actions of Vitamin D on Regulatory T Lymphocyte Responses
939(1)
Actions of Vitamin D on B Lymphocytes
940(1)
Actions of Vitamin D on the Immune Microenvironment and the Function of Antigen-Presenting Cells
940(1)
Vitamin D and Vaccine Responses
941(1)
Translational Studies as a Window to Study Effects of Vitamin D on Adaptive Immunology
942(1)
Disparity Between Association, Translational, and Clinical Studies
942(2)
Ultraviolet B Versus Oral Vitamin D Supplementation---Effects on the Adaptive Immune System
944(1)
Vitamin D as a Temporal Regulator of Adaptive Immune Responses
944(1)
Conclusions
944(1)
References
945(6)
105 Vitamin D and Innate Immunity
Kathryn Zavala
Aria Vazirnia
Philip T. Liu
Introduction
951(1)
Mycobacteria
951(1)
Mechanisms for Pathogen Sensing
952(2)
Barrier Function and Associated Infectious Diseases
954(1)
Innate Immune Activity of 1,25-Dihydroxyvitamin D
954(3)
Vitamin D Pathway and Tuberculosis
957(2)
Vitamin D Pathway and Leprosy
959(1)
History of Vitamin D, Sunshine, and Tuberculosis Treatment
960(1)
Conclusion
961(1)
References
961(8)
106 Vitamin D and Diabetes
An-Sofie Vanherwegen
Conny Gysemans
Chantal Mathieu
Introduction
969(1)
Vitamin D and Genetic Predisposition to Diabetes
970(1)
Vitamin D, the Beta Cell, and Insulin Resistance in Type 2 Diabetes
971(3)
Vitamin D as an Immune Modulator in Type 1 Diabetes
974(6)
Conclusions and Clinical Perspectives
980(1)
References
981(9)
107 Vitamin D and Multiple Sclerosis
Colleen E. Hayes
Faye E. Nashold
Introduction
990(1)
Genes and Environment in Multiple Sclerosis
991(1)
Vitamin D and Multiple Sclerosis Risk and Severity
992(3)
Vitamin D Signaling in the Immune and Nervous Systems
995(2)
Vitamin D Mechanisms of Immune Regulation
997(3)
Vitamin D Mechanisms of Neuroprotection
1000(2)
Rising Multiple Sclerosis Incidence in Women
1002(1)
Sex-Based Differences in Multiple Sclerosis and the Role of Estrogen
1002(1)
Vitamin D and Estrogen Synergy for T Cell Self-Tolerance
1003(2)
Declining Vitamin D Status and Rising Multiple Sclerosis Incidence
1005(2)
Vitamin D and Multiple Sclerosis Prevention
1007(2)
Conclusions and Unanswered Questions
1009(1)
Acknowledgments
1009(1)
References
1010(15)
108 Vitamin D and Inflammatory Bowel Disease
Margherita T. Cantorna
Danny Bruce
Introduction
1025(1)
What Is Inflammatory Bowel Disease?
1025(1)
Who Gets Inflammatory Bowel Disease?
1026(2)
The Gut Epithelium, Commensals, and Inflammatory Bowel Disease
1028(1)
The Immune Response and Inflammatory Bowel Disease
1028(1)
Vitamin D Regulates T Cell Responsiveness
1029(1)
Experimental Models of Inflammatory Bowel Disease
1030(1)
Vitamin D and the Microbiota
1031(1)
Current Treatments for Inflammatory Bowel Disease
1032(1)
Vitamin D as a Treatment Option for Inflammatory Bowel Disease
1033(1)
Conclusions
1033(1)
References
1033(4)
109 Psoriasis and Other Skin Diseases
Jorg Reichrath
Michael F. Holick
Introduction/Historical Overview
1037(1)
Pathogenesis of Psoriasis
1038(1)
The Vitamin D System in Normal and Psoriatic Skin
1038(2)
Physiological and Pharmacological Actions of Vitamin D Analogs in Normal and Psoriatic Skin
1040(3)
Clinical Use of 1,25(OH)2D3 and Its Analogs in Psoriasis and Other Skin Diseases
1043(2)
Vitamin D Analog Therapy in Other Skin Diseases
1045(1)
Evaluation of New Vitamin D Analogs, With Less Calcemic Activity, Which Can Be Used for the Treatment of Hyperproliferative Skin Disorders
1046(1)
Conclusion
1047(1)
References
1047(9)
XII THERAPEUTIC APPLICATIONS AND NEW ADVANCES
110 Sunlight Protection by Vitamin D Compounds
Rebecca S. Mason
Mark S. Rybchyn
Katie M. Dixon
Introduction
1056(1)
DNA Damage by Ultraviolet Radiation
1056(2)
DNA Repair
1058(2)
Ultraviolet-Induced Immune Suppression
1060(1)
Synthesis and Metabolism of Vitamin D Compounds in Skin
1061(1)
The Vitamin D System and Photocarcinogenesis
1061(2)
Vitamin D Compounds Reduce Several Types of Ultraviolet-Induced DNA Damage
1063(2)
Vitamin D Compounds and UV-Induced Immune Suppression
1065(1)
Pathways---Evidence for Involvement of Nonclassical Pathways
1066(2)
Conclusions
1068(1)
References
1069(8)
111 Vitamin D, Cardiovascular Disease, and Hypertension
Stefan Pilz
Introduction
1077(1)
Historical Perspective
1078(1)
Mechanistic Effects
1078(2)
Observational Studies
1080(2)
Mendelian Randomization Studies
1082(1)
Randomized Controlled Trials
1083(2)
Future Perspective
1085(1)
Conclusions
1086(1)
References
1087(9)
112 Vitamin D, Acute Respiratory Infection, and Asthma/Chronic Obstructive Pulmonary Disease
Carlos A. Camargo Jr.
Introduction
1096(1)
Common Respiratory Disorders
1096(3)
Vitamin D and Lung Development
1099(1)
Vitamin D and Acute Respiratory Infection
1100(3)
Vitamin D and Asthma
1103(4)
Vitamin D and Chronic Obstructive Pulmonary Disease
1107(2)
Potential Mechanisms
1109(3)
Future Research
1112(2)
Summary
1114(1)
Acknowledgments
1114(1)
References
1114(7)
113 Vitamin D and Muscle Performance in Athletes
Lisa Ceglia
Roberto Toni
Introduction
1121(1)
Historical Links Between Vitamin D and Athletic Performance
1121(1)
Basic Research Influencing Interest in Vitamin D in Athletic Performance
1122(2)
Clinical Research Influencing Interest in Vitamin D in Athletic Performance
1124(1)
Recent Clinical Research in Athletes
1124(3)
Conclusion
1127(1)
References
1127(4)
114 Vitamin D: Presence and Function in the Eye
Jawaher A. Alsalem
Saaeha Rauz
Graham R. Wallace
Introduction
1131(1)
Vitamin D and the Eye
1132(1)
Ocular Infection
1133(1)
Dry Eye Disease
1133(2)
Cataract
1135(1)
Glaucoma
1136(1)
Uveitis
1136(2)
Age-Related Macular Degeneration
1138(3)
Diabetic Retinopathy
1141(1)
Conclusion
1142(1)
References
1143(4)
115 Adult Vitamin D Deficiency and Adverse Brain Outcomes
Natalie J. Groves
John J. Mcgrath
Thomas H.J. Burne
Introduction
1147(1)
Epidemiology
1147(4)
Preclinical Studies
1151(3)
Future Directions
1154(1)
Conclusion
1155(1)
References
1155(4)
116 Vitamin D in Pregnancy and Lactation: Moving Into the Future
Bruce W. Hollis
Carol L. Wagner
Introduction
1159(1)
Vitamin D Nomenclature and Metabolism
1160(1)
Vitamin D Metabolism During Pregnancy When Compared With the Nonpregnant State Including Lactation
1160(2)
Obstetrical "Paranoia" Regarding Vitamin D Administration During Pregnancy
1162(1)
Observational Studies Suggesting the Function of Vitamin D Extended Beyond Calcium Homeostasis During Pregnancy
1162(1)
Randomized Controlled Trials Investigating Vitamin D Supplementation During Pregnancy
1163(2)
Supplementing Vitamin D During Pregnancy to Prevent Childhood Asthma
1165(3)
Neurodevelopment and Autoimmune Consequences
1168(1)
Current Recommendation for Vitamin D Supplementation During Pregnancy
1168(1)
Vitamin D Requirements of the Mother/Infant Dyad During Lactation
1169(1)
Altering the Vitamin D Content of Human Milk
1169(1)
Interventional and RCTs to Determine if Maternal Vitamin D Supplementation Can Supply Adequate Vitamin D to the Nursing Infant
1169(2)
Current Recommendation for Maternal Vitamin D Supplementation During Lactation
1171(1)
Summary
1171(1)
Financial Support
1172(1)
References
1172
117 Vitamin D and Critically Intensive Care Unit Patients
111
Kenneth B. Christopher
Introduction
1177
Prevalence of Vitamin D Deficiency in the Critically
111
Patients
1178
Vitamin D Deficiency Risk Factors in the Critically
111
Patients
1178(1)
Vitamin D Mechanism in Critical Illness
1179(1)
Antimicrobial Peptides
1180(1)
β-Defensin 2
1181(1)
Cathelicidin
1181(1)
Inflammasome Activation
1181(1)
Metabolomics, Transcriptomics, and Epigenetics of Vitamin D
1182(1)
Assay
1183(1)
Observational Data
1183(1)
Vitamin D and Critical Illness Outcomes
1183(1)
Sepsis
1183(1)
Acute Kidney Injury
1183(1)
Acute Lung Injury
1184(1)
Interventional Data
1184(2)
Dose in Critical Illness
1186(1)
Is Vitamin D Supplementation Safe?
1186(1)
Conclusions 1187(1)
References 1187(8)
Index for Volume 2 1195
Prof. Hewisons work focuses on different facets of vitamin D physiology, including classical skeletal effects and non-classical extra-skeletal effects. He has a particular interest in the interaction between vitamin D and the immune system, where antigen-presenting cells such as dendritic cells and macrophages synthesize active vitamin D (calcitriol) and also express the nuclear receptor for calcitriol (VDR). Vitamin D can therefore act as an endogenous regulator of both innate and adaptive immunity by enhancing antibacterial activity, and modulating antigen presentation and T lymphocyte function. Crucially these responses are highly dependent on the bioavailability of vitamin D, and Prof. Hewison has hypothesized that immune function is influenced by vitamin D status in humans. His group is using a variety of models to test this hypothesis including basic molecular and cell analyses, and vitamin D supplementation trials in human cohorts. A key objective of his work is to increase awareness of vitamin D-deficiency in the UK population. Roger Bouillon, MD, PhD, FRCP, biography Roger Bouillon is professor (emeritus since 2010) in endocrinology (internal medicine) at the University and University Hospital of the Catholic University of Leuven (K.U.Leuven) in Belgium. He is a member of the Royal Academy of Medicine (Belgium) and a Fellow of the Royal College of Physicians (London). He was a founding member and later President of the European Board of Endocrinology (UEMS 1988-2002). He was a member of several European Science Foundation Committees (Board member of the European Medical Research Council) and of the European Space Agency Life Science working group till 2012. He is past-president of the International Bone and Mineral Society (2011-13 ) and is co-organizer of the vitamin D workshop. He was vice president for research of the University of Leuven from 1995-2005. He is coauthor of more than 500 peer reviewed articles that generated about 26,000 ISI citations and a H index of 82. The topics of his research deal with (1) several aspects of diabetes an endocrinology in general but his main research focus deals with (2) hormonal aspects of bone and calcium homeostasis and this spans the spectrum of basic, translational and clinical research. (3) Vitamin D is a major research focus throughout his scientific career. Papers: Edward Giovannucci's research focuses on how nutritional, genetic, environmental and lifestyle factors relate to various malignancies, especially those of the prostate and large bowel. Much of his work is centered on large ongoing cohort studies, including the Nurses Health Study, the Health Professionals Follow-Up Study and the Physicians Health Study. A specific area of interest is the etiologic mechanisms underlying the relation between modifiable factors and cancer risk. His work has included the study of how nutrition and other lifestyle factors impact on cancer risk and progression by influencing levels of insulin, insulin-like growth factors, vitamin D metabolites, and steroid hormones. Another area of interest is how nutrients may interact with genetic susceptibilities in determining an individual's risk. David Goltzman is Professor in the Departments of Medicine and Physiology of McGill University, Director of the McGill Centre for Bone and Periodontal Research, and Senior Physician in the Endocrine Division of the Department of Medicine of the McGill University Health Centre. His research has focused on the hormonal regulation of mineral and skeletal homeostasis, and he has made many important contributions to our knowledge of parathyroid hormone (PTH), PTH related peptide and vitamin D, which have had major impact on our understanding of a variety of metabolic bone diseases. He is also principal investigator of the Canadian Multicentre Osteoporosis Study (CaMos) which examines the demographics, development, risk factors and outcomes of osteoporosis. Dr. Goltzman has received various honours and awards, including the Aurbach Award of the US Endocrine Society, the Raisz Award of the American Society for Bone and Mineral Research (ASBMR), fellowship in the Royal Society of Canada and in the Canadian Academy of Health Sciences, the Order of Canada, an honorary professorship from Nanjing University and the degree of Doctor Honoris Causa from the University of Athens. He is a past President of the ASBMR, the Canadian Society of Clinical Investigation and the Canadian Society of Endocrinology and Metabolism.