Front cover

Botulinum Toxin

Copyright page

Contributors

Preface

Foreword

DEVELOPMENT OF BOTULINUM TOXIN

Contents

CHAPTER 1 - Multiple Steps in the Blockade of Exocytosis by Botulinum Neurotoxins

INTRODUCTION

MULTIPHASIC MECHANISM OF ACTION OF BOTULINUM NEUROTOXINS

MOLECULAR BASIS FOR THE THERAPEUTIC EFFECTIVENESS OF BoNT/A

INHIBITION OF PEPTIDE RELEASE FROM SENSORY NEURONS BY CERTAIN BoNTS REFLECT THEIR ANTINOCICEPTIVE POTENTIAL

CONCLUSIONS

References

CHAPTER 2 - Molecular Structures and Functional Relationships of Botulinum Neurotoxins

INTRODUCTION

STRUCTURE OF BOTULINUM NEUROTOXINS

STRUCTURE-FUNCTION RELATIONSHIPS

CONCLUSIONS

References

CHAPTER 3 - Botulinum Neurotoxin—a Modular Nanomachine

INTRODUCTION

BoNT CHANNEL ACTIVITY UNDER CONDITIONS PREVALENT AT ENDOSOMES

RETRIEVAL OF ENDOPEPTIDASE ACTIVITY OF BoNT LC IN THE TRANS COMPARTMENT AT THE COMPLETION OF TRANSLOCATION

RELEASE OF CARGO FROM CHAPERONE IS NECESSARY FOR PRODUCTIVE TRANSLOCATION

DISCRETE INTERMEDIATES DURING BoNT TRANSLOCATION REVEAL THE CONFORMATIONAL DYNAMICS OF CARGO-CHANNEL INTERACTIONS

THE BoNT HC CHANNEL AS A CHAPERONE FOR THE LC PROTEASE

BoNT HC CHANNEL AS A TARGET FOR INTERVENTION

CONCLUDING REMARKS

References

CHAPTER 4 - Interactions Between Botulinum Neurotoxins and Synaptic Vesicle Proteins

INTRODUCTION

MODULAR ARCHITECTURE AND MECHANISM OF ACTION

SNARES AND CA2+-TRIGGERED NEUROTRANSMITTER RELEASE

CNT LC PROTEASES

RECEPTOR INTERACTIONS

CONCLUSIONS

References

CHAPTER 5 - Immune Recognition of Botulinum Neurotoxins A and B: Molecular Elucidation of Immune Protection Against the Toxins

INTRODUCTION

METHOD FOR LOCALIZING THE REGIONS OF IMMUNE RECOGNITION ON THE H CHAINS OF BoNT/A AND /B, AND REGIONS THAT BIND TO CELL RECEPTOR

REGIONS ON THE H CHAIN OF BoNT/A THAT BIND ANTITOXIN ANTIBODIES FROM DIFFERENT HOST SPECIES

MOLECULAR SPECIFICITY OF NEUTRALIZING AND NON-NEUTRALIZING ANTI-BoNT/A ANTIBODIES

THE SYNAPTOSOME-BINDING REGIONS ON THE H CHAIN OF BoNT/A

THE REGIONS ON THE H-CHAIN OF BoNT/A RECOGNIZED BY ANTIBODIES OF CERVICAL DYSTONIA PATIENTS WHO BECAME UNRESPONSIVE TO BoNT/A TREATMENT

A NEW ASSAY FOR NEUTRALIZING AND NON-NEUTRALIZING ANTI-BoNT/A ABS BASED ON INHIBITION OF BoNT/A BINDING TO SYNAPTOSOMES

A PEPTIDE-BASED IMMUNOASSAY FOR ANTI-BoNT/A ANTIBODIES

ANTIBODY BINDING REGIONS ON THE BoNT/B H CHAIN AND THEIR RELATIONSHIP TO RECEPTOR BINDING

CONCLUSIONS

References

CHAPTER 6 - Biology and Clinical Pharmacology of Botulinum Neurotoxin Type C and Other Non-A/Non-B Botulinum Neurotoxins

INTRODUCTION

BOTULINUM NEUROTOXIN SEROTYPE F

BOTULINUM NEUROTOXIN SEROTYPE C

OTHER BOTULINUM NEUROTOXIN SEROTYPES

DISCUSSION

References

CHAPTER 7 - Effects of Botulinum Toxin on Central Nervous System Function

INTRODUCTION

STUDIES OF SPINAL CORD FUNCTION

STUDIES OF CORTICAL MOTOR FUNCTION

STUDIES OF MUSCLE AFFERENTS

CONCLUSIONS

References

CHAPTER 8 - Botulinum Neurotoxin Treatment of Cranial-Cervical Dystonia

INTRODUCTION

ETIOLOGY

PATHOPHYSIOLOGY

TREATMENT

BOTULINUM TOXIN FOR BLEPHAROSPASM

BOTULINUM TOXIN FOR OROMANDIBULAR DYSTONIA (See Chapter 16)

BOTULINUM TOXIN FOR CERVICAL DYSTONIA

CONCLUSION

References

CHAPTER 9 - Botulinum Neurotoxin Treatment of Limb and Occupational Dystonias

INTRODUCTION

FOCAL HAND DYSTONIA

SIGNS AND SYMPTOMS

EPIDEMIOLOGY AND GENETICS

DIFFERENTIAL DIAGNOSIS

TREATMENT

BOTULINUM TOXIN TREATMENT OF UPPER EXTREMITY SEGMENTAL DYSTONIA

SUMMARY

References

CHAPTER 10 - Botulinum Neurotoxin in Tremors, Tics, Hemifacial Spasm, Spasmodic Dysphonia, and Stuttering

INTRODUCTION

HEMIFACIAL SPASM

SPASMODIC DYSPHONIA

SPASMODIC LARYNGEAL DYSPNEA

STUTTERING

VOCAL TREMORS

TREMOR

TICS

References

CHAPTER 11 - Upper Limb Skin and Musculoskeletal Consequences of the Upper Motor Neuron Syndrome

INTRODUCTION

COMBINED EFFECTS OF POSITIVE AND NEGATIVE SIGNS: THE NET TORQUE IMBALANCE CONCEPT

ASSOCIATED REACTIONS

FLEXOR AND EXTENSOR REFLEXES

STRETCH-SENSITIVE SPASTICITY

SPASTIC CO-CONTRACTION

SPASTIC DYSTONIA

RHEOLOGIC TISSUE CHANGES AND CONTRACTURE

SKIN AND MUSCULOSKELETAL COMPLICATIONS IN THE UPPER LIMB

SKIN INTEGRITY

BONE AND JOINT INTEGRITY

PHYSICAL PRESSURE AND INJURY

SOFT TISSUE INTEGRITY

PERSONAL CARE INTEGRITY

BODY IMAGE INTEGRITY

CONCLUSION

References

CHAPTER 12 - Clinical Trials of Botulinum Toxin in Adult Spasticity

INTRODUCTION

AVAILABLE OUTCOME MEASURES

POST-STROKE SPASTICITY

SPASTICITY IN MULTIPLE SCLEROSIS

SPASTICITY IN OTHER DISORDERS

SAFETY OF BoNT IN SPASTICITY

CONCLUSIONS AND OUTLOOK

References

CHAPTER 13 - Biological and Mechanical Pathologies in Spastic Skeletal Muscle: The Functional Implications of Therapeutic Neurotoxins

INTRODUCTION

SKELETAL MUSCLE PLASTICITY

MUSCLE FIBER TYPE AND FIBER SIZE CHANGES WITH SPASTICITY

MECHANICAL CHANGES IN SPASTIC MUSCLE

MUSCLE FUNCTIONAL RESPONSES TO NEUROTOXIN THERAPY

SPASTIC MUSCLE FIBER TYPE SIZE CHANGES IN RESPONSE TO NEUROTOXIN THERAPY

PRACTICAL CONSIDERATIONS IN NEUROTOXIN DELIVERY

IMAGING AND NEUROTOXIN DELIVERY

SUMMARY AND FUTURE DIRECTIONS

References

CHAPTER 14 - Treatment of Motor Disorders in Cerebral Palsy with Botulinum Neurotoxin

INTRODUCTION

CEREBRAL PALSY: DEFINITIONS

CLASSIFYING CEREBRAL PALSY

CEREBRAL PALSY AND THE UPPER MOTOR NEURON SYNDROME

CEREBRAL PALSY AND PROGRESSIVE MUSCULOSKELETAL PATHOLOGY

MEASUREMENT OF SPASTICITY IN CEREBRAL PALSY

INTERNATIONAL CLASSIFICATION OF FUNCTIONING AND QUALITY OF LIFE

CEREBRAL PALSY AND MULTIDISCIPLINARY MANAGEMENT

CEREBRAL PALSY AND THE SPASTICITY COMPASS

BOTULINUM NEUROTOXIN IN CEREBRAL PALSY

MANAGEMENT OF MUSCLE HYPERACTIVITY IN THE LOWER LIMBS WITH BOTULINUM NEUROTOXIN A

BOTULINUM NEUROTOXIN A IN THE UPPER LIMB IN CEREBRAL PALSY

ADVERSE EVENTS OF BOTULINUM NEUROTOXIN THERAPY IN CEREBRAL PALSY

BOTULINUM NEUROTOXIN A AS AN ANALGESIC AGENT IN CEREBRAL PALSY

CONCLUSION

References

CHAPTER 15 - Clinical Experience and Recent Advances in the Management of Gait Disorders with Botulinum Neurotoxin

INTRODUCTION

PATTERNS OF UPPER MOTOR NEURON DYSFUNCTION

BOTULINUM TOXIN

PHENOL

CONCLUSIONS

References

CHAPTER 16 - Treatment of Oromandibular Dystonia, Bruxism, and Temporomandibular Disorders with Botulinum Toxin

INTRODUCTION

CLINICAL SYNDROMES

BOTULINUM TOXIN AND TREATMENT OF TEMPOROMANDIBULAR DISORDERS AND OROMANDIBULAR DYSTONIA

CLINICAL EXPERIENCE

SIDE/ADVERSE EFFECTS

CONCLUSIONS

References

CHAPTER 17 - Botulinum Toxin in Headache Management

INTRODUCTION

PATHOPHYSIOLOGY OF HEADACHE DISORDERS

TREATMENT OF HEADACHE

BOTULINUM TOXIN IN HEADACHE DISORDERS

SUMMARY

References

CHAPTER 18 - Botulinum Toxin Therapy in Gastrointestinal Disorders

INTRODUCTION

CRICOPHARYNGEAL DYSPHAGIA

ACHALASIA

DIFFUSE ESOPHAGEAL SPASM AND OTHER PUTATIVE DISORDERS OF ESOPHAGEAL MOTILITY

GASTROPARESIS

OBESITY

SPHINCTER OF ODDI DYSFUNCTION

ANAL FISSURE

OTHER ANORECTAL DISORDERS

CONCLUSIONS

References

CHAPTER 19 - Mechanism of Action of Botulinum Neurotoxin in the Lower Urinary Tract

INTRODUCTION

ACTION OF BOTULINUM NEUROTOXIN ON URINARY TRACT STRIATED VERSUS SMOOTH MUSCLE

EFFECT OF BOTULINUM NEUROTOXIN ON THE DETRUSOR MUSCLE

FROM CELLULAR ACTION TO CLINICAL EFFECT

MECHANISM OF ACTION

ADVERSE LOCAL EFFECTS

CONCLUSION

References

CHAPTER 20 - Botulinum Toxin in Overactive Bladder

SUMMARY

INTRODUCTION

MECHANISM OF ACTION

BOTULINUM NEUROTOXIN: INTRADETRUSOR INJECTION TECHNIQUE

NEUROGENIC DETRUSOR OVERACTIVITY

IDIOPATHIC OVERACTIVE BLADDER WITH OR WITHOUT DETRUSOR OVERACTIVITY

BOTULINUM TOXIN TYPE B AND OVERACTIVE BLADDER

DURATION OF EFFECT AND REPEATED INJECTION

SIDE EFFECTS OF BOTULINUM TOXIN-A INJECTIONS

COST OF BOTULINUM NEUROTOXIN THERAPY

CONCLUSION

References

CHAPTER 21 - Botulinum Toxin in the Treatment of Chronic Pelvic Pain Syndromes

INTRODUCTION AND THERAPEUTIC RATIONALE

GENITOURINARY PAIN SYNDROMES TREATED WITH BOTULISM NEUROTOXIN TYPE A

INJECTION TECHNIQUES

SUMMARY

References

CHAPTER 22 - Application of Botulinum Toxin in the Prostate

INTRODUCTION

EXPERIMENTAL EVIDENCE

PROSTATE APPLICATIONS

POSSIBLE ADDITIONAL USES OF BOTULINUM NEUROTOXIN TYPE A FOR THE TREATMENT OF PROSTATIC DISEASES

CONCLUSIONS

ACKNOWLEDGMENT

References

CHAPTER 23 - Clinical Application of Botulinum Neurotoxin in the Treatment of Myofascial Pain Syndromes

INTRODUCTION

PHYSICAL EXAMINATION

GENERAL TREATMENT APPROACH TO MYOFASCIAL PAIN SYNDROME

POTENTIAL DISEASE COMPLICATIONS

SUMMARY

References

CHAPTER 24 - Botulinum Toxin for Osteoarticular Pain

INTRODUCTION

NEUROBIOLOGY OF OSTEOARTICULAR PAIN

RATIONALE FOR SELECTING BOTULINUM TOXIN TO TREAT OSTEOARTICULAR PAIN

MEASURING PAIN BEHAVIORS IN ANIMAL MODELS OF ARTHRITIS PAIN

EFFECTS OF INTRA-ARTICULAR BOTULINUM TOXIN TYPE A IN HUMAN ARTHRITIS PAIN

EFFECTS OF INTRA-ARTICULAR BOTULINUM NEUROTOXIN TYPE A IN REFRACTORY KNEE PROSTHESIS PAIN

References

CHAPTER 25 - Botulinum Neurotoxin in the Management of Hyperhidrosis and Other Hypersecretory Disorders

INTRODUCTION

SWEATING

SIALORRHEA

FUTURE DIRECTIONS

References

CHAPTER 26 - Botulinum Neurotoxin for Dermatologic and Cosmetic Disorders

INTRODUCTION

AVAILABLE BOTULINUM NEUROTOXIN PRODUCTS

PRINCIPLES OF AESTHETIC USES

FACIAL AESTHETICS

FACIAL ANATOMY

GENERAL PRINCIPLES AND TREATMENT GUIDELINES

COSMETIC FACIAL INJECTIONS

COMPLICATIONS WITH AESTHETIC BOTULINUM NEUROTOXIN THERAPY

References

CHAPTER 27 - The Role of Botulinum Toxin in Wound Healing

INTRODUCTION

DYNAMIC TENSION

CASE STUDY OF A FOREHEAD INJURY

CLINICAL TRIAL

CASE STUDY OF AN INJURY TO THE LOWER FACE

OTHER USES FOR BOTULINUM TOXIN IN WOUND HEALING

CONCLUSION

References

CHAPTER 28 - Understanding Botulinum Neurotoxin Mechanism of Action and Structure to Enhance Therapeutics and Improve Care

INTRODUCTION

CREATING THERAPEUTIC PROTEINS BASED ON THE NEUROTOXINS

CHRONIC PAIN

MUCUS HYPERSECRETION AND CHRONIC RESPIRATORY DISEASE

CONCLUSIONS

METHODS

References

CHAPTER 29 - Unmet Needs and Challenges in the Therapeutic Use of Botulinum Neurotoxins

INTRODUCTION

INJECTION TECHNIQUE

MEASURES OF TREATMENT RESPONSE

GAPS IN CLINICAL EVIDENCE

FUTURE CLINICAL TRIALS

References

CHAPTER 30 - Potential New Therapeutic Indications for Botulinum Neurotoxins

INTRODUCTION

NEUROLOGY

SURGERY

OTOLARYNGOLOGY

DERMATOLOGY

OTHER CONDITIONS

VETERINARY USE

ACKNOWLEDGMENT

References

CHAPTER 31 - Botulism Vaccines and the Immune Response

INTRODUCTION

PENTAVALENT (ABCDE) BOTULINUM TOXOID

STRATEGIES AND PROGRESS TOWARDS DEVELOPING FUTURE VACCINE CANDIDATES

SUMMARY

ACKNOWLEDGMENTS

References

CHAPTER 32 - Properties of Pharmaceutical Products of Botulinum Neurotoxins

INTRODUCTION

MANUFACTURING OF BOTULINUM TOXIN CONTAINING PHARMACEUTICALS

DRUG SUBSTANCE

DRUG PRODUCT

PROTEIN LOAD AND SPECIFIC POTENCY

IMMUNOLOGIC PROPERTIES

References

CHAPTER 33 - Comparative Clinical Trials of Botulinum Toxins

INTRODUCTION

BOTULINUM NEUROTOXIN BRANDS: MOUSE UNITS

COMPARATIVE EFFECTS OF BOTULINUM NEUROTOXIN IN A SINGLE MUSCLE

COMPARATIVE BoNT EFFECTS IN BLEPHAROSPASM AND HEMIFACIAL SPASM

COMPARATIVE EFFECTS OF BOTULINUM NEUROTOXIN IN CERVICAL DYSTONIA

CONCLUSION

References

CHAPTER 34 - Tetanus Toxin

INTRODUCTION

CLINICAL TETANUS

PREVENTION OF CLINICAL TETANUS

TETANUS TOXIN

DELIVERY VECTORS FROM TETANUS TOXIN

TETANUS TOXIN AS A POTENTIAL THERAPEUTIC

ACKNOWLEDGMENTS

References

CHAPTER 35 - Bungarotoxins

INTRODUCTION

HISTORY

CHEMISTRY

TOXICOLOGY

TARGETS AND PHYSIOLOGIC EFFECTS OF ALPHA-BUNGAROTOXIN

ROLE OF a7-RECEPTORS IN PATHOLOGY

POTENTIAL CLINICAL APPLICATION OF DRUGS THAT TARGET nAChRs: TREATMENT OF LOWER URINARY TRACT DYSFUNCTION

References

CHAPTER 36 - Biology and Pharmacology of Conotoxins

INTRODUCTION

BIOLOGY AND ECOLOGY OF CONE SNAILS: SOURCE OF PEPTIDE DIVERSITY

SUPERFAMILIES OF CONOPEPTIDES

OVERVIEW OF MAIN TARGETS OF CONUS PEPTIDES: VOLTAGE-GATED AND LIGAND-GATED ION CHANNELS

CONOTOXINS TARGETED TO VOLTAGE-GATED ION CHANNELS

OTHER CONUS PEPTIDES REPORTED TO TARGET VOLTAGE-GATED ION CHANNELS

CONOPEPTIDES TARGETED TO LIGAND-GATED ION CHANNELS

CONANTOKINS: N-METHYL-D-ASPARTATE RECEPTOR ANTAGONISTS

OTHER BIOLOGICALLY ACTIVE CONSTITUENTS OF CONUS VENOMS

THERAPEUTIC APPLICATIONS OF CONOTOXINS

ACKNOWLEDGMENT

References

CHAPTER 37 - Therapeutic Applications of Conotoxins

INTRODUCTION

CONCLUSION

References

CHAPTER 38 - Spider and Wasp Neurotoxins

INTRODUCTION

TOXINS ACTING ON NA+ CHANNELS

CALCIUM CHANNEL TOXINS

POTASSIUM CHANNEL TOXINS

CHLORIDE CHANNEL TOXINS

GLUTAMATE RECEPTOR AND TRANSPORTERS TOXINS

GABA RECEPTOR AND TRANSPORTERS TOXINS

WASP NEUROTOXINS

CONCLUSIONS AND FUTURE PERSPECTIVES

References

Index

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