Revisión documental sobre el uso de la toxina butolínica tipo A producida por Clostridium botulinum en el campo estético.
El tratamiento con toxina botulínica tipo A, es uno de los más empleados para mejorar arrugas gracias a que es efectivo y seguro, así como genera poco dolor en comparación con otros tratamientos estéticos. En Colombia y en el mundo, hay un aumento en la demanda del producto, siendo necesario un mayo...
- Autores:
-
Ricaurte Solano, Nathaly
- Tipo de recurso:
- Trabajo de grado de pregrado
- Fecha de publicación:
- 2019
- Institución:
- Colegio Mayor de Cundinamarca
- Repositorio:
- Repositorio Colegio Mayor de Cundinamarca
- Idioma:
- spa
- OAI Identifier:
- oai:repositorio.unicolmayor.edu.co:unicolmayor/3735
- Acceso en línea:
- https://repositorio.unicolmayor.edu.co/handle/unicolmayor/3735
- Palabra clave:
- Abobotulinumtoxin A
Incobotulinumtoxin A
Toxina botulínica
Clostridium botulinum
Onabotulinumtoxin A
- Rights
- closedAccess
- License
- Derechos Reservados - Universidad Colegio Mayor de Cundinamarca, 2019
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Revisión documental sobre el uso de la toxina butolínica tipo A producida por Clostridium botulinum en el campo estético. |
| title |
Revisión documental sobre el uso de la toxina butolínica tipo A producida por Clostridium botulinum en el campo estético. |
| spellingShingle |
Revisión documental sobre el uso de la toxina butolínica tipo A producida por Clostridium botulinum en el campo estético. Abobotulinumtoxin A Incobotulinumtoxin A Toxina botulínica Clostridium botulinum Onabotulinumtoxin A |
| title_short |
Revisión documental sobre el uso de la toxina butolínica tipo A producida por Clostridium botulinum en el campo estético. |
| title_full |
Revisión documental sobre el uso de la toxina butolínica tipo A producida por Clostridium botulinum en el campo estético. |
| title_fullStr |
Revisión documental sobre el uso de la toxina butolínica tipo A producida por Clostridium botulinum en el campo estético. |
| title_full_unstemmed |
Revisión documental sobre el uso de la toxina butolínica tipo A producida por Clostridium botulinum en el campo estético. |
| title_sort |
Revisión documental sobre el uso de la toxina butolínica tipo A producida por Clostridium botulinum en el campo estético. |
| dc.creator.fl_str_mv |
Ricaurte Solano, Nathaly |
| dc.contributor.advisor.none.fl_str_mv |
Hernández Rojas, Edith |
| dc.contributor.author.none.fl_str_mv |
Ricaurte Solano, Nathaly |
| dc.subject.lemb.none.fl_str_mv |
Abobotulinumtoxin A Incobotulinumtoxin A |
| topic |
Abobotulinumtoxin A Incobotulinumtoxin A Toxina botulínica Clostridium botulinum Onabotulinumtoxin A |
| dc.subject.proposal.spa.fl_str_mv |
Toxina botulínica Clostridium botulinum Onabotulinumtoxin A |
| description |
El tratamiento con toxina botulínica tipo A, es uno de los más empleados para mejorar arrugas gracias a que es efectivo y seguro, así como genera poco dolor en comparación con otros tratamientos estéticos. En Colombia y en el mundo, hay un aumento en la demanda del producto, siendo necesario un mayor número de documentos que informen a los pacientes. Por lo tanto, el propósito de este trabajo fue hacer una revisión bibliográfica sobre el uso de la toxina botulínica tipo A producida por Clostridium botulinum en el campo estético. La información recolectada de las fuentes bibliográficas fue clasificada por año, país, idioma, fuente, formato y temática. Las fuentes bibliográficas fueron conformadas por diversos tipos de documentos. El proceso de recolección de la información reportó el uso de diferentes formulaciones comerciales de la toxina botulínica tipo A, indicaciones de los fabricantes y efectos adversos de la aplicación de la toxina botulínica. También se reportaron los genes codificantes, la regulación en la producción, la estructura y mecanismo de acción de la toxina botulínica, lo cual es fundamental para comprender la fabricación y los efectos de las diferentes formulaciones. Finalmente se encontró que la mayoría de las investigaciones provenían de EE. UU., ya que según las estadísticas referenciadas, es el país con mayor demanda y por lo tanto, requería mayor cantidad de investigaciones. Esta revisión bibliográfica se enfoca en las generalidades del uso de la toxina botulínica tipo A en el campo cosmético, así como los diferentes parámetros para realizar el procedimiento. |
| publishDate |
2019 |
| dc.date.issued.none.fl_str_mv |
2019-07 |
| dc.date.accessioned.none.fl_str_mv |
2021-11-26T21:37:16Z |
| dc.date.available.none.fl_str_mv |
2021-11-26T21:37:16Z |
| dc.type.spa.fl_str_mv |
Trabajo de grado - Pregrado |
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http://purl.org/coar/resource_type/c_7a1f |
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http://purl.org/coar/version/c_970fb48d4fbd8a85 |
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Text |
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info:eu-repo/semantics/bachelorThesis |
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https://purl.org/redcol/resource_type/TP |
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http://purl.org/coar/resource_type/c_7a1f |
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https://repositorio.unicolmayor.edu.co/handle/unicolmayor/3735 |
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60084 |
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https://repositorio.unicolmayor.edu.co/handle/unicolmayor/3735 |
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spa |
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spa |
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Truong D, Hallett M, Zachary C, Dressler D. Manual Of Botulinum Toxin Therapy. 2nd Ed. Nueva York: Cambridge University Press; 2014. Carter A, Peck M. Genomes, neurotoxins and biology of Clostridium botulinum Group I and Group II. Res Microbiol. 2015; 166(4):303-317. Scuderi N, Toth BA. International Textbook of Aesthetic Surgery. Berlin: Springer Nature; 2016. Fabbrocini G, De Padova MP, Tosti A. Nonsurgical lip and eye rejuvenation techniques. 1a ed. Suiza: Springer International Publishing; 2016. Stringer S, Carter A, Webb M, Wachnicka E, Crossman L, Sebaihia M, Peck M. Genomic and physiological variability within Group II (non-proteolytic) Clostridium botulinum. BCM Genomics. 2013; 14(333):1-18. Doyle MP, Buchanan RL. Food Microbiology: Fundamentals and Frontiers. 4 th ed. Washington D.C.: ASM Press; 2013. Hill KK, Xie G, Foley BT, Smith TJ. Genetic diversity within the botulinum neurotoxin-producing bacteria and their neurotoxins. Toxicon. 2015; 107(Part A):2-8. Connan C, Denève C, Mazuet C, Popoff M. Regulation of toxin synthesis in Clostridium botulinum and Clostridium tetani. Toxicon. 2013; 75 (3): 90-100. Connan C, Popoff M. Two-component systems and toxinogenesis regulation in Clostridium botulinum. Research in Microbiology, Elsevier. 2015; 166(4): 332-343. Carter G, Cheung J, Larcombe S, Lyras D. Regulation of toxin production in the pathogenic clostridia. Molecular Microbiology. 2014; 91(2): 221–231. Fredrick C, Lín G, Johnson E. Regulation of Botulinum Neurotoxin Synthesis and Toxin Complex Formation by Arginine and Glucose in Clostridium botulinum ATCC 3502. Appl Environ Microbiol. 2017; 83(13): 1-11. Zhang Z, Dahlsten E, Korkeala H, Lindström M. Positive regulation of botulinum neurotoxin gene expression by CodY in 2 Clostridium botulinum ATCC 3502. Appl. Environ. Microbiol. 2014; 80(24):7651-7658. Hill K, Smith TJ. Genetic Diversity Within Clostridium botulinum Serotypes, Botulinum Neurotoxin Gene Clusters and Toxin Subtypes. En: Rummel A, Binz T, editores. Botulinum Neurotoxins, Current Topics in Microbiology and Immunology. Vol 364. Berlin: Springer; 2013. p 1-20. Peck MW, Smith TJ, Anniballi F, Austin JW, Bano L, Bradshaw M, Cuervo P, Cheng LW, Derman Y, Dorner BG, Fisher A, Hill KK, Kalb SR, Korkeala H, Lindstrom M, Lista F, Lúquez C, Mazuet C, Pirazzini M, Popoff MR, Rossetto O, Rummel A, Sesardic D, Singh BR, Stringer SC. Historical perspectives and guidelines for botulinum neurotoxin subtype nomenclature. Toxins. 2017; 9(38):1-21. Peng Chen Z, Morris G, Rodriguez R, Wagle Shukla A, Tapia-Núñez J, Okun M. Emerging Opportunities for Serotypes of Botulinum Neurotoxins. Toxins. 2012; 4(11):1196-1222. Zhang Y, Gardberg AS, Edwards TE, Sankaran B, Robinson H, Varnum SM, Buchko GW. Structural insights into the functional role of the Hcn sub-domain of the receptor-binding domain of the botulinum neurotoxin mosaic serotype C/D. Biochimie, Elsevier. 2013; 95(7):1379-1385. Li T, Tian R, Cai K, Wang Q, Chen F, Fang H, Luo S, Li Z, Wang D, Hou X, Wang H. The effect of pH on growth of Clostridium botulinum type A and expression of bontA and botR during different growth stages. Foodborne Pathogens and Disease. 2013; 10(8):692-697. Woudstra C, Le Maréchal C, Souillard R, Anniballi F, Auricchio B, Bano L, Bayon-Auboyer MH, Koene M, Mermoud I, Brito RB, Lobato FCF, Silva ROS, Dorner MB, Fach P. Investigation of Clostridium botulinum group III's mobilome content. Anaerobe, Elsevier. 2018; 49(): 71-77. Wongrattanakamon P, Nimmanpipug P, Sirithunyalug B, Jiranusornkul S. Molecular modeling elucidates the cellular mechanism of synaptotagmin SNARE inhibition: a novel plausible route to anti‐wrinkle activity of botox‐like cosmetic active molecules. Mol Cell Biochem. 2018; 442(1-2):97-109. Suzuki T, Nagano T, Niwa K, Uchino M, Tomizawa M, Sagane Y, Watanabe T. Construction of “Toxin Complex” in a Mutant Serotype C Strain of Clostridium botulinum Harboring a Defective Neurotoxin Gene. Current Microbiology. 2017; 74(1):49-54. Carter GP, Larcombe S, Jayawardena D, Awad MM, Songer JG, Lyras D. Expression of the large clostridial toxins is controlled by conserved regulatory mechanisms. Int J Med Microbiol. 2014; 304(8):1147-1159. Chellapandi P, Prisilla A. Clostridium botulinum type A-virulome-gut interactions: A systems biology insight. Human Microbiome Journal, Elsevier. 2018; 7-8():15-22. Woudstra C, Le Maréchal C, Souillard R, Bayon-Auboyer MH, Anniballi F, Auricchio B, De Medici D, Bano L, Koene M, Sansonetti MH, Desoutter D, Hansbauer EM, Dorner MB, Dorner BG, Fach P. Molecular Gene Profiling of Clostridium botulinum Group III and Its Detection in Naturally Contaminated Samples Originating from Various European Countries. Applied and Environmental Microbiology. 2015; 81(7):2495-2505. Long SS. Part III: Etiologic Agents of Infectious Diseases. En: Long SS, Fischer M, Prober CG, editores. Principles and Practice of Pediatric Infectious Diseases. 5th Ed. EE.UU.: Elsevier; 2018. p 999-1006. Kuo YC, Kuo HC. Adverse Events of Intravesical OnabotulinumtoxinA Injection between Patients with Overactive Bladder and Interstitial Cystitis- Different Mechanisms of Action of Botox on Bladder Dysfunction?. Toxins. 2016; 8(3):-. Pirazzini M, Rossetto O, Eleopra R, Montecucco C. Botulinum neurotoxins: biology, pharmacology and toxicology. Pharmacol Rev. 2017; 69(2): 200-235. Harii K, Kawashima M, Furuyama N, Lei X, Hopfinger R, Lee E. OnabotulinumtoxinA (Botox) in the Treatment of Crow’s Feet Lines in Japanese Subjects. Aesthetic Plastic Surgery. 2017; 41(5):1186-1197. Ihekwaba AEC, Mura I, Walshaw J, Peck MW, Barker GC. An Integrative Approach to Computational Modelling of the Gene Regulatory Network Controlling Clostridium botulinum Type A1 Toxin Production. PLOS computational biology. 2016; 12(11):1-23. Dahlsten E, Isokallio M, Somervuo P, Lindstrom M, Korkeala H. Transcriptomic Analysis of (Group I) Clostridium botulinum ATCC 3502 Cold Shock Response. PLOS ONE. 2014; 9(2):1-13. Clostridium botulinum [Internet]. NCBI Taxonomy Browser. Disponible en: https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=696040 Nahai F, Lorenc P, Kenkel J, Fagien S, Hirmand H, Nestor M, Sclafani A, Sykes J, Waldorf H. A review of onabotulinumtoxinA (Botox). Aesthetic Surgery Journal. 2013; 33(1):9-12. Barash JR, Arnon SS. A Novel Strain of Clostridium botulinum That Produces Type B and Type H Botulinum Toxins. The Journal of Infectious Diseases. 2013; 209(2):183-191. Stern D, Weisemann J, Le Blanc A, von Berg L, Mahrhold S, Piesker J, Laue M, Luppa PB, Dorner MB, Dorner BG, Rummel A. A lipid-binding loop of botulinum neurotoxin serotypes B, DC and G is an essential feature to confer their exquisite potency. PLOS Pathog. 2018; 14(5)1-25. Sakaguchi Y, Suzuki T, Yamamoto Y, Nishikawa A, Oguma K. Genomics of Clostridium botulinum group III strains. Res Microbiol, Elsevier. 2015; 166(4):318-325. Pirazzini M, Tehran DA, Leka O, Zanetti G, Rossetto O, Montecucco C. On the translocation of botulinum and tetanus neurotoxins across the membrane of acidic intracellular compartments. Biochimica et Biophysica Acta (BBA). 2016; 1858(3):467-474. Gustafsson R, Berntsson RP-A, Martínez-Carranza M, Tekle GE, Odegrip R, Johnson EA, Stenmark P. Crystal structures of OrfX2 and P47 from a Botulinum neurotoxin OrfX‐type gene cluster. FEBS Lett. 2017; 591(22):3781-3792. Aoishi K, Takahashi H, Hato N, Gyo K, Yokota M, Ozaki S, Suzuki M. Treatment of allergic rhinitis with intranasal infusion of botulinum toxin type A in mice. Life Sciences, Elsevier. 2016; 147():132-136. Grenda T, Kukier E, Kwiatek. Methods and difficulties in detection of Clostridium botulinum and its toxins. Polish Journal of Veterinary Sciences. 2014; 17(1)195-205. Giordani F, Fillo S, Anselmo A, Palozzi AM, Fortunato A, Gentile B, Tehran DA, Ciammaruconi A, Spagnolo F, Pittiglio V, Anniballi F, Auricchio B, De Medici D, Lista F. Genomic characterization of Italian Clostridium botulinum group I strains. Infection, genetics and evolution, Elsevier. 2015; 36():62-71. Takehara M, Takagishi T, Seike S, Oda M, Sakagushi Y, Hisatsune J, Ochi S, Kobayashi K, Nagahama M. Cellular Entry of Clostridium perfringens Iota- Toxin and Clostridium botulinum C2 Toxin. Toxins. 2017;9(8):1-9. Whitman WB, Goodfellow M, Kämpfer P, Busse HJ, Trujillo ME, Ludwing W, Suzuki K. Bergey’s Manual of Systematic Bacteriology. Vol 5, parts A & B. 2nd ed. Nueva York: Springer-Verlag; 2012. Bistrom A, Moisander-Jylha AM, Heinikainen S, Pelkola K, Raunio-Saarnisto M. Isolation of Clostridium limosum from an outbreak of metritis in farmed mink. Acta Vet Scand. 2016; 58(49):2-4. Weimer PJ, Stevenson DM. Isolation, characterization, and quantification of Clostridium kluyveri from the bovine rumen. Appl Microbiol Biotechnol. 2012; 94(2):461–466. Lawson PA, Citron DM, Tyrrell KL, Finegold SM. Reclassification of Clostridium difficile as Clostridioides difficile (Hall and O’Toole 1935) Prévot 1938. Anaerobe, Elsevier. 2016; 40():95-99. Woudstra C, Le Maréchal C, Souillard R, Bayon-Auboyer MH, Mermoud I, Desoutter D, Fach P. New insights into the genetic diversity of Clostridium botulinum Group III through extensive genome exploration. Front. Microbiol. 2016; 7(757):1-10. Carruthers J, Carruthers A, Dover JS, Alam M. Procedures in Cosmetic Dermatology. 4th ed. China: Elsevier; 2018. Nahai F, Lorenc P, Kenkel JM, Fagien S, Hirmand H, Nestor MS, Sclafani AP, Sykes JM, Waldorf HA. A review of AbobotulinumtoxinA (Dysport). Aesthetic Surgery Journal. 2013; 33(1):13-17. Datta Gupta A, Visvanathan R. Botulinum toxin for foot dystonia in patients with Parkinson’s disease having deep brain stimulation: a case series and a pilot study. J Rehabil Med. 2016;48(6):559-562. Kollewe K, Mohammadi B, Köller S, Pickenbrock H, Dengler R, Dressler D. Blepharospasm: long-term treatment with either Botox, Xeomin or Disport. J Neural Transm, Springer. 2015; 122(3):427-431. Rosow DE, Pechman A, Saint-Victor S, Lo K, Lundy DS, Casiano RR. Factors Influencing Botulinum Toxin Dose Instability in Spasmodic Dysphonia Patients. Journal of Voice. 2015; 29(3):352-355. Teemul TA, Patel R, Kanatas A, Carter LM. Management of oromandibular dystonia with botulinum A toxin: a series of cases. Br J Oral Maxillofac Surg, Science Direct. 2016; 54(10):1080-1084. Ababneh OH, Cetinkaya A, Kulwin DR. Long-term efficacy and safety of botulinum toxin A injections to treat blepharospasm and hemifacial spasm. Clinical and Experimental Ophtalmology. 2014; 42(3):254-261. Chan KH, Liang C, Wilson P, Higgins D, Allen GC. Long-term safety and efficacy data on botulinum toxin type A: an injection for sialorrhea. JAMA Otolaryngol Head Neck Surg. 2013; 139(2):134-138. Hooft N, Schmidt ES, Bremner RM. Achalasia in pregnancy: Botulinum toxin A injection of lower esophageal sphincter. Hindawi Publishing Corporation. 2015;():-. Dressler D, Tacik P, Adib Saberi F. Botulinum toxin therapy of cervical dystonia: comparing onabotulinumtoxinA (Botox®) and incobotulinumtoxinA (Xeomin®). J Neural Transm (Vienna). 2014; 121(1):29-31. Martínez-Ramírez D, Giugni JC, Hastings E, Wagle Shukla A, Malaty IA, Okun MS, Rodríguez RL. Comparable Botulinum Toxin Outcomes between Primary and Secondary Blepharospasm: A Retrospective Analysis. Tremor Other Hyperkinet Mov (N Y). 2014; 4(286):1-7. Pandey S, Sharma S. Botulinum toxin in Meige's syndrome: A video-based case series. Neurol India. 2018; 66(1):71-76. Ravindra P, Jackson BL, Parkinson RJ. Botulinum toxin type A for the treatment of non-neurogenic overactive bladder: does using onabotulinumtoxinA (Botox®) or abobotulinumtoxinA (Dysport®) make a difference?. BJU Int. 2013; 112(1):94-99. Merino PS, Vera RE, Mariñas LG, Gómez de Liaño PS, Escribano JV. Botulinum toxin for treatment of restrictive strabismus. Journal of Optometry. 2017; 10(3):189-193. Shafik Elridy A, Eldin Zaki RG, Fazwy Elshinawy R. Comparison of the Clinical Efficacy of Abobotulinumtoxin A (ABO) and Onabotulinumtoxin A (ONA) in the Treatment of Crow’s Feet Wrinkles: A Split-Face Study. Seminars in Ophthalmology. 2017; 33(2):1-9. Del Río Navarrete MP. Botulinum Toxin for Mentum and Perioral Area. En: Issa M, Tamura B, editores. Botulinum Toxins, Fillers and Related Substances. Clinical Approaches and Procedures in Cosmetic Dermatology. Alemania: Springer; 2017. p 1-10. Nahai F, Lorenc P, Kenkel JM, Fagien S, Hirmand H, Nestor M, Sclafani A, Sykes JM, Waldorf HA. IncobotulinumtoxinA in clinical literature. Aesthetic Surgery Journal. 2013; 33(1):23-34. Rostedt Punga A, Alimohammadi M, Fagrell D, Nyberg F, Rees D, Wong C. A Randomized, Comparative Study to Evaluate Efficacy and Safety of Two Injection Volumes of AbobotulinumtoxinA in Treatment of Glabellar Lines. Dermatol Surg. 2016; 42(8):967-976. Trindade de Almeida A, Carruthers J, Cox SE, Goldman M, Wheeler S, Gallagher C. Patient Satisfaction and Safety With Aesthetic OnabotulinumtoxinA After At Least 5 Years: A Retrospective Cross-Sectional Analysis of 4,402 Glabellar Treatments. Dermatologic Surgery. 2015; 41():S19-S28. Susmita A, Devi Kolli NN, Meka S, Chakravarthi SP, Kattimani VS, Lingamaneni KP, Shaik LS. An Evaluation of Use of Botulinum Toxin Type A in the Management of Dynamic Forehead Wrinkles - A Clinical Study. J Clin Diagn Res. 2016; 10(10):127-131. Robinson DM, Horne DF, Rohrer TE. Shaping of the Eyebrows with Botulinum Toxin Type A (BoNT-A). En: Hartstein ME, Massry G, Holds J, editores. Pearls and Pitfalls in Cosmetic Oculoplastic Surgery. Nueva York: Springer; 2015. p 413-415. ühne U, Imhof M. IncobotulinumtoxinA (Xeomin/Bocouture). En: Cohen J, Ozog D, editores. Botulinum toxins: Cosmetic and Clinical Applications. 1 st ed.: John Wiley & Sons Ltd.; 2017. p 79-95. Emer JJ, Axibal E, Marmur ES, Waldorf H. OnabotulinumtoxinA (Botox) in Dermatology. En: Cohen J, Ozog D, editors. Botulinum toxins: Cosmetic and Clinical Applications. 1 st ed.: John Wiley & Sons Ltd.; 2017. p 357-367. Jones D, Kerscher M, Geister T, Hast M, Weissenberger P. Efficacy of IncobotulinumtoxinA for the Treatment of Glabellar Frown Lines in Male Subjects: Post-Hoc Analyses From Randomized, Double-Blind Pivotal Studies. Dermatologic Surgery. 2017; 43():S235-S241. Ascher B, Kestemont P, Boineau D, Bodokh I, Stein A, Heckmann M, Dendorfer M, Pavicic T, Volteau M, Tse A, Picaut P, Rzany B. Liquid Formulation of AbobotulinumtoxinA Exhibits a Favorable Efficacy and Safety Profile in Moderate to Severe Glabellar Lines: A Randomized, Double-Blind, Placebo- and Active Comparator-Controlled Trial. Aesthetic Surgery Journal. 2018; 38(2):183-191. Nahai F, Lorenc P, Kenkel JM, Fagien S, Hirmand H, Nestor SM, Sclafani AP, Sykes JM, Waldorf HA. Incobotulinumtoxin A (Xeomin). Aesthetic Surgery Journal. 2013; 33(1):18-22. Pavicic T, Prager W, Klöppel M, Ravichandran S, Galatoire O. IncobotulinumtoxinA use in aesthetic indications in daily practice: a European multicenter, noninterventional, retrospective study. Clin Cosmet Investig Dermatol. 2015; 8():135-142. Streker M, Luebberding S, Krueger N, Harrington L, Kerscher M. Patient- Reported Outcomes After IncobotulinumtoxinA Treatment for Upper Facial Wrinkles. Dermatologic Surgery. 2015; 41():29-38. Gubanova E, Haddad Tabet M, Bergerova Y, Moiseieva O, Chemeris A, Sanches E, Sharova A, Rodríguez Pose L, Raymond R, Prygova I, Carlisle I. Assessment of Subject and Physician Satisfaction after Long-Term Treatment of Glabellar Lines with AbobotulinumtoxinA (Dysport®/Azzalure®): Primary Results of the APPEAL Noninterventional Study. Aesthetic Plastic Surgery. 2018; 42(6): 1672–1680. Wilson A, Chang B, Taglienti A, Chin B, Chang C, Folsom N, Percec I. A Quantitative Analysis of OnabotulinumtoxinA, AbobotulinumtoxinA, and IncobotulinumtoxinA: A Randomized, Double-Blind, Prospective Clinical Trial of Comparative Dynamic Strain Reduction. Plast Reconstr Surg. 2016; 137(5):1424-1433. Berkowitz D. Botox Nation. Changing the face of America. New York University Press. 2017. The International Study on Aesthetic/Cosmetic Procedures Performed in 2016 [Internet]. ISAPS International Society of Aesthetic Plastic Surgery. Disponible en: https://www.isaps.org/wp- content/uploads/2019/03/ISAPS_2017_International_Study_Cosmetic_Proc edures_NEW.pdf Plastic Surgery Statistics Report 2017 [Internet]. ASPS American Society of Plastic Surgeons. Disponible en: https://www.plasticsurgery.org/documents/News/Statistics/2018/plastic- surgery-statistics-report-2018.pdf Pickett A. Botulinum Toxin as a Clinical Product: Manufacture and Pharmacology. En: Foster KA, editores. Clinical Applications of Botulinum Neurotoxin. Vol 5. EE.UU.: Springer; 2014. p 7-49. Garcia-Murray E, Velasco-Villasenor ML, Acevedo B, Luna S, Lee J, Waugh JM, Hornfeldt CS. Safety and efficacy of RT002, an injectable botulinum toxin type A, for treating glabellar lines: results of a phase 1/2, open-label, sequential dose- escalation study. Dermatol Surg. 2015; 41(Suppl 1):S47-S55. Paul Lorenc Z. Abstract: DWP-450, Purified Botulinum Toxin Type A, for the Treatment of Moderate-to-Severe Glabellar Lines in Adult Subjects: Results from Two Randomized, Double-Blind, Placebo-Controlled, Single Dose Phase III Safety and Efficacy Studies. Plast Reconstr Surg Glob Open. 2017; 5(9 Suppl):193-194. Carruthers J, Carruthers A. Treatment of glabellar frown lines with C. botulinum-A exotoxin. J Dermatol Surg Oncol. 1992; 18(1)17-21. Blitzer A, Brin MF, Keen MS, Aviv JE. Botulinum toxin for the treatment of hyperfunctional lines of the face. Arch Otolaryngol Head Neck Surg. 1993; 119(9):1018-1022. Blitzer A, Binder WJ, Aviv JE, Keen MS, Brin MF. The management of hyperfunctional facial lines with botulinum toxin. A collaborative study of 210 injection sites in 162 patients. Arch Otolaryngol Head Neck Surg. 1997; 123(4):389-392. Carruthers J, Carruthers A. Aesthetic botulinum A toxin in the mid and lower face and neck. Dermatol Surg. 2003; 29(5):468-476. Kim NH, Chung JH, Park RH, Park JB. The use of botulinum toxin type A in aesthetic mandibular contouring. Plast Reconstr Surg. 2005; 115(3):919-930. Ascher B, Talarico S, Cassuto D, Escobar S, Hexsel D, Jaén P, Monheit GD, Rzany B, Viel M. International consensus recommendations on the aesthetic usage of botulinum toxin type A (Speywood Unit)-Part I: Upper facial wrinkles. J Eur Acad Dermatol Venereol. 2010; 24(11):1278-1284. Dorizas A, Krueger N, Sadick NS. Aesthetic uses of the botulinum toxins. Dermatol Clin. 2014; 32(1):23-36. |
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Hernández Rojas, Edithbb445075fe399249f42457b22b7525f9Ricaurte Solano, Nathaly61449f2bf6a604d5a85df1045a619d3c2021-11-26T21:37:16Z2021-11-26T21:37:16Z2019-07https://repositorio.unicolmayor.edu.co/handle/unicolmayor/373560084El tratamiento con toxina botulínica tipo A, es uno de los más empleados para mejorar arrugas gracias a que es efectivo y seguro, así como genera poco dolor en comparación con otros tratamientos estéticos. En Colombia y en el mundo, hay un aumento en la demanda del producto, siendo necesario un mayor número de documentos que informen a los pacientes. Por lo tanto, el propósito de este trabajo fue hacer una revisión bibliográfica sobre el uso de la toxina botulínica tipo A producida por Clostridium botulinum en el campo estético. La información recolectada de las fuentes bibliográficas fue clasificada por año, país, idioma, fuente, formato y temática. Las fuentes bibliográficas fueron conformadas por diversos tipos de documentos. El proceso de recolección de la información reportó el uso de diferentes formulaciones comerciales de la toxina botulínica tipo A, indicaciones de los fabricantes y efectos adversos de la aplicación de la toxina botulínica. También se reportaron los genes codificantes, la regulación en la producción, la estructura y mecanismo de acción de la toxina botulínica, lo cual es fundamental para comprender la fabricación y los efectos de las diferentes formulaciones. Finalmente se encontró que la mayoría de las investigaciones provenían de EE. UU., ya que según las estadísticas referenciadas, es el país con mayor demanda y por lo tanto, requería mayor cantidad de investigaciones. Esta revisión bibliográfica se enfoca en las generalidades del uso de la toxina botulínica tipo A en el campo cosmético, así como los diferentes parámetros para realizar el procedimiento.RESUMEN 11 INTRODUCCIÓN 12 2. OBJETIVOS 15 2.1. OBJETIVO GENERAL 15 2.2. OBJETIVOS ESPECÍFICOS 15 3. ANTECEDENTES 16 4. MARCO REFERENCIAL 18 4.1. Clostridium 18 4.1.1. Botulismo 20 5. TOXINA BOTULÍNICA 21 5.1. Serotipos de toxina botulínica 21 5.2. Genes codificantes de la toxina botulínica 21 5.3. Regulación de la producción de toxinas en C. botulinum 23 5.3.1. Estímulos ambientales y nutricionales 23 5.3.2. Sistemas de transducción de señales de dos componentes 23 5.3.3. Percepción de quórum 24 5.3.4. Factores sigma (accesorios 24 5.4. Estructura de la toxina botulínica 24 5.5. Mecanismo de acción de la toxina botulínica 26 5.5.1. Unión a la membrana celular 26 5.5.2. Internalización a la neurona 27 5.5.3. Translocación de la toxina dentro del endosoma 27 5.5.4. Proteólisis de las proteínas SNARE específicas 28 6. APLICACIONES DE LA TOXINA BOTULÍNICA 28 6.1. Formulaciones de la toxina botulínica 29 6.1.1. Onabotulinumtoxin A 30 6.1.1.1. Manejo de Onabotulinumtoxin A 31 6.1.1.2. Inicio y duración del efecto 31 6.1.2. Abobotulinumtoxin A 32 6.1.3. Incobotulinumtoxin A 32 6.1.3.1. Difusión del producto 33 6.2. Fabricación del producto 33 6.3. Contraindicaciones generales previas al tratamiento 34 6.4. Consideraciones inmunológicas 34 6.5. Jeringas y agujas 35 6.6. Uso cosmético de la toxina botulínica 35 6.8.1. Toxina botulínica para arrugas periorales 35 6.8.1.1. Aplicación de la toxina botulínica en el músculo orbicular de la boca 36 6.8.1.2. Aplicación de la toxina botulínica en el músculo depresor del ángulo de la boca 36 6.8.1.3. Aplicación de la toxina botulínica en el músculo mentoniano 37 6.8.1.4. Aplicación de la toxina botulínica en las bandas del platisma 38 6.8.1.5. Aplicación de la toxina botulínica en el músculo cigomático mayor y menor 38 6.8.2. Toxina botulínica para arrugas perioculares 39 6.8.2.1. Aplicación de la toxina botulínica en el músculo corrugador superciliar 39 6.8.2.2. Aplicación de la toxina botulínica en el músculo frontal 40 6.8.2.3. Aplicación de la toxina botulínica en el músculo orbicular de los ojos 40 6.8.2.4. Modificación farmacológica de las cejas 41 6.8.2.5. Aplicación de la toxina botulínica en el músculo nasal 41 6.8.3. Complicaciones de la aplicación de la toxina botulínica a nivel cosmético 42 6.8.3.1. Complicaciones de inyectar los músculos de la zona periocular 42 6.8.3.1.1. Ptosis del párpado, diplopía y estrabismo 42 6.8.3.1.2. Xeroftalmia iatrogénica o síndrome de ojo seco 43 6.8.3.1.3. Ptosis de la ceja 43 6.8.3.2. Complicaciones de inyectar los músculos periorales 44 6.8.3.2.1. Ptosis en los labios 44 6.8.3.2.2. Deterioro en los músculos del cuello 44 6.8.3.3. Complicaciones raras 45 6.9. Otros usos de la toxina botulínica 45 7. DISEÑO METODOLÓGICO 47 7.1. Tipo de investigación 47 7.1.1. Universo 47 7.1.2. Población 47 7.1.3. Muestra 47 7.2. Criterios de selección de la bibliografía revisada 47 7.2.1. Criterios de inclusión 47 7.2.2. Criterios de exclusión 48 7.3. Procedimientos 48 7.3.1. Búsqueda de la información 48 7.3.2. Selección de documentos 48 7.3.3. Revisión bibliográfica 48 7.3.4. Análisis de la información 49 8. RESULTADOS 50 8.1. Tipo de documento 50 8.2. Año de publicación 50 8.3. Idioma de publicación 51 8.4. País de publicación 52 8.5. Base de datos 53 8.6. Tema de investigación 54 8.7. Publicaciones sobre el gen bont 55 8.8. Documentación relacionada con mecanismos de regulación 56 8.9. Documentación relacionada con el mecanismo de acción 57 8.10. Aplicaciones cosméticas de la toxina botulínica tipo A 58 8.11. Complicaciones luego del tratamiento con la toxina botulínica tipo A 58 8.12. Aplicaciones clínicas de la toxina botulínica tipo A 59 8.13. Formulaciones empleadas a nivel cosmético 60 8.14. Formulaciones empleadas a nivel clínico 61 9. DISCUSIÓN 62 10. CONCLUSIONES 68 RECOMENDACIONES 69 BIBLIOGRAFÍA 70PregradoBacteriólogo(a) y Laboratorista Clínico80p.application/pdfspaUniversidad Colegio Mayor de CundinamarcaFacultad de Ciencias de la SaludBogotá DCBacteriología y Laboratorio ClínicoDerechos Reservados - Universidad Colegio Mayor de Cundinamarca, 2019https://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/closedAccessAtribución-NoComercial-CompartirIgual 4.0 Internacional (CC BY-NC-SA 4.0)http://purl.org/coar/access_right/c_14cbRevisión documental sobre el uso de la toxina butolínica tipo A producida por Clostridium botulinum en el campo estético.Trabajo de grado - Pregradohttp://purl.org/coar/resource_type/c_7a1fhttp://purl.org/coar/version/c_970fb48d4fbd8a85Textinfo:eu-repo/semantics/bachelorThesishttps://purl.org/redcol/resource_type/TPinfo:eu-repo/semantics/publishedVersionTruong D, Hallett M, Zachary C, Dressler D. Manual Of Botulinum Toxin Therapy. 2nd Ed. Nueva York: Cambridge University Press; 2014.Carter A, Peck M. Genomes, neurotoxins and biology of Clostridium botulinum Group I and Group II. Res Microbiol. 2015; 166(4):303-317.Scuderi N, Toth BA. International Textbook of Aesthetic Surgery. Berlin: Springer Nature; 2016.Fabbrocini G, De Padova MP, Tosti A. Nonsurgical lip and eye rejuvenation techniques. 1a ed. Suiza: Springer International Publishing; 2016.Stringer S, Carter A, Webb M, Wachnicka E, Crossman L, Sebaihia M, Peck M. Genomic and physiological variability within Group II (non-proteolytic) Clostridium botulinum. BCM Genomics. 2013; 14(333):1-18.Doyle MP, Buchanan RL. Food Microbiology: Fundamentals and Frontiers. 4 th ed. Washington D.C.: ASM Press; 2013.Hill KK, Xie G, Foley BT, Smith TJ. Genetic diversity within the botulinum neurotoxin-producing bacteria and their neurotoxins. Toxicon. 2015; 107(Part A):2-8.Connan C, Denève C, Mazuet C, Popoff M. Regulation of toxin synthesis in Clostridium botulinum and Clostridium tetani. Toxicon. 2013; 75 (3): 90-100.Connan C, Popoff M. Two-component systems and toxinogenesis regulation in Clostridium botulinum. Research in Microbiology, Elsevier. 2015; 166(4): 332-343.Carter G, Cheung J, Larcombe S, Lyras D. Regulation of toxin production in the pathogenic clostridia. Molecular Microbiology. 2014; 91(2): 221–231.Fredrick C, Lín G, Johnson E. Regulation of Botulinum Neurotoxin Synthesis and Toxin Complex Formation by Arginine and Glucose in Clostridium botulinum ATCC 3502. Appl Environ Microbiol. 2017; 83(13): 1-11.Zhang Z, Dahlsten E, Korkeala H, Lindström M. Positive regulation of botulinum neurotoxin gene expression by CodY in 2 Clostridium botulinum ATCC 3502. Appl. Environ. Microbiol. 2014; 80(24):7651-7658.Hill K, Smith TJ. Genetic Diversity Within Clostridium botulinum Serotypes, Botulinum Neurotoxin Gene Clusters and Toxin Subtypes. En: Rummel A, Binz T, editores. Botulinum Neurotoxins, Current Topics in Microbiology and Immunology. Vol 364. Berlin: Springer; 2013. p 1-20.Peck MW, Smith TJ, Anniballi F, Austin JW, Bano L, Bradshaw M, Cuervo P, Cheng LW, Derman Y, Dorner BG, Fisher A, Hill KK, Kalb SR, Korkeala H, Lindstrom M, Lista F, Lúquez C, Mazuet C, Pirazzini M, Popoff MR, Rossetto O, Rummel A, Sesardic D, Singh BR, Stringer SC. Historical perspectives and guidelines for botulinum neurotoxin subtype nomenclature. Toxins. 2017; 9(38):1-21.Peng Chen Z, Morris G, Rodriguez R, Wagle Shukla A, Tapia-Núñez J, Okun M. Emerging Opportunities for Serotypes of Botulinum Neurotoxins. Toxins. 2012; 4(11):1196-1222.Zhang Y, Gardberg AS, Edwards TE, Sankaran B, Robinson H, Varnum SM, Buchko GW. Structural insights into the functional role of the Hcn sub-domain of the receptor-binding domain of the botulinum neurotoxin mosaic serotype C/D. Biochimie, Elsevier. 2013; 95(7):1379-1385.Li T, Tian R, Cai K, Wang Q, Chen F, Fang H, Luo S, Li Z, Wang D, Hou X, Wang H. The effect of pH on growth of Clostridium botulinum type A and expression of bontA and botR during different growth stages. Foodborne Pathogens and Disease. 2013; 10(8):692-697.Woudstra C, Le Maréchal C, Souillard R, Anniballi F, Auricchio B, Bano L, Bayon-Auboyer MH, Koene M, Mermoud I, Brito RB, Lobato FCF, Silva ROS, Dorner MB, Fach P. Investigation of Clostridium botulinum group III's mobilome content. Anaerobe, Elsevier. 2018; 49(): 71-77.Wongrattanakamon P, Nimmanpipug P, Sirithunyalug B, Jiranusornkul S. Molecular modeling elucidates the cellular mechanism of synaptotagmin SNARE inhibition: a novel plausible route to anti‐wrinkle activity of botox‐like cosmetic active molecules. Mol Cell Biochem. 2018; 442(1-2):97-109.Suzuki T, Nagano T, Niwa K, Uchino M, Tomizawa M, Sagane Y, Watanabe T. Construction of “Toxin Complex” in a Mutant Serotype C Strain of Clostridium botulinum Harboring a Defective Neurotoxin Gene. Current Microbiology. 2017; 74(1):49-54.Carter GP, Larcombe S, Jayawardena D, Awad MM, Songer JG, Lyras D. Expression of the large clostridial toxins is controlled by conserved regulatory mechanisms. Int J Med Microbiol. 2014; 304(8):1147-1159.Chellapandi P, Prisilla A. Clostridium botulinum type A-virulome-gut interactions: A systems biology insight. Human Microbiome Journal, Elsevier. 2018; 7-8():15-22.Woudstra C, Le Maréchal C, Souillard R, Bayon-Auboyer MH, Anniballi F, Auricchio B, De Medici D, Bano L, Koene M, Sansonetti MH, Desoutter D, Hansbauer EM, Dorner MB, Dorner BG, Fach P. Molecular Gene Profiling of Clostridium botulinum Group III and Its Detection in Naturally Contaminated Samples Originating from Various European Countries. Applied and Environmental Microbiology. 2015; 81(7):2495-2505.Long SS. Part III: Etiologic Agents of Infectious Diseases. En: Long SS, Fischer M, Prober CG, editores. Principles and Practice of Pediatric Infectious Diseases. 5th Ed. EE.UU.: Elsevier; 2018. p 999-1006.Kuo YC, Kuo HC. Adverse Events of Intravesical OnabotulinumtoxinA Injection between Patients with Overactive Bladder and Interstitial Cystitis- Different Mechanisms of Action of Botox on Bladder Dysfunction?. Toxins. 2016; 8(3):-.Pirazzini M, Rossetto O, Eleopra R, Montecucco C. Botulinum neurotoxins: biology, pharmacology and toxicology. Pharmacol Rev. 2017; 69(2): 200-235.Harii K, Kawashima M, Furuyama N, Lei X, Hopfinger R, Lee E. OnabotulinumtoxinA (Botox) in the Treatment of Crow’s Feet Lines in Japanese Subjects. Aesthetic Plastic Surgery. 2017; 41(5):1186-1197.Ihekwaba AEC, Mura I, Walshaw J, Peck MW, Barker GC. An Integrative Approach to Computational Modelling of the Gene Regulatory Network Controlling Clostridium botulinum Type A1 Toxin Production. PLOS computational biology. 2016; 12(11):1-23.Dahlsten E, Isokallio M, Somervuo P, Lindstrom M, Korkeala H. Transcriptomic Analysis of (Group I) Clostridium botulinum ATCC 3502 Cold Shock Response. PLOS ONE. 2014; 9(2):1-13.Clostridium botulinum [Internet]. NCBI Taxonomy Browser. Disponible en: https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?id=696040Nahai F, Lorenc P, Kenkel J, Fagien S, Hirmand H, Nestor M, Sclafani A, Sykes J, Waldorf H. A review of onabotulinumtoxinA (Botox). Aesthetic Surgery Journal. 2013; 33(1):9-12.Barash JR, Arnon SS. A Novel Strain of Clostridium botulinum That Produces Type B and Type H Botulinum Toxins. The Journal of Infectious Diseases. 2013; 209(2):183-191.Stern D, Weisemann J, Le Blanc A, von Berg L, Mahrhold S, Piesker J, Laue M, Luppa PB, Dorner MB, Dorner BG, Rummel A. A lipid-binding loop of botulinum neurotoxin serotypes B, DC and G is an essential feature to confer their exquisite potency. PLOS Pathog. 2018; 14(5)1-25.Sakaguchi Y, Suzuki T, Yamamoto Y, Nishikawa A, Oguma K. Genomics of Clostridium botulinum group III strains. Res Microbiol, Elsevier. 2015; 166(4):318-325.Pirazzini M, Tehran DA, Leka O, Zanetti G, Rossetto O, Montecucco C. On the translocation of botulinum and tetanus neurotoxins across the membrane of acidic intracellular compartments. Biochimica et Biophysica Acta (BBA). 2016; 1858(3):467-474.Gustafsson R, Berntsson RP-A, Martínez-Carranza M, Tekle GE, Odegrip R, Johnson EA, Stenmark P. Crystal structures of OrfX2 and P47 from a Botulinum neurotoxin OrfX‐type gene cluster. FEBS Lett. 2017; 591(22):3781-3792.Aoishi K, Takahashi H, Hato N, Gyo K, Yokota M, Ozaki S, Suzuki M. Treatment of allergic rhinitis with intranasal infusion of botulinum toxin type A in mice. Life Sciences, Elsevier. 2016; 147():132-136.Grenda T, Kukier E, Kwiatek. Methods and difficulties in detection of Clostridium botulinum and its toxins. Polish Journal of Veterinary Sciences. 2014; 17(1)195-205.Giordani F, Fillo S, Anselmo A, Palozzi AM, Fortunato A, Gentile B, Tehran DA, Ciammaruconi A, Spagnolo F, Pittiglio V, Anniballi F, Auricchio B, De Medici D, Lista F. Genomic characterization of Italian Clostridium botulinum group I strains. Infection, genetics and evolution, Elsevier. 2015; 36():62-71.Takehara M, Takagishi T, Seike S, Oda M, Sakagushi Y, Hisatsune J, Ochi S, Kobayashi K, Nagahama M. Cellular Entry of Clostridium perfringens Iota- Toxin and Clostridium botulinum C2 Toxin. Toxins. 2017;9(8):1-9.Whitman WB, Goodfellow M, Kämpfer P, Busse HJ, Trujillo ME, Ludwing W, Suzuki K. Bergey’s Manual of Systematic Bacteriology. Vol 5, parts A & B. 2nd ed. Nueva York: Springer-Verlag; 2012.Bistrom A, Moisander-Jylha AM, Heinikainen S, Pelkola K, Raunio-Saarnisto M. Isolation of Clostridium limosum from an outbreak of metritis in farmed mink. Acta Vet Scand. 2016; 58(49):2-4.Weimer PJ, Stevenson DM. Isolation, characterization, and quantification of Clostridium kluyveri from the bovine rumen. Appl Microbiol Biotechnol. 2012; 94(2):461–466.Lawson PA, Citron DM, Tyrrell KL, Finegold SM. Reclassification of Clostridium difficile as Clostridioides difficile (Hall and O’Toole 1935) Prévot 1938. Anaerobe, Elsevier. 2016; 40():95-99.Woudstra C, Le Maréchal C, Souillard R, Bayon-Auboyer MH, Mermoud I, Desoutter D, Fach P. New insights into the genetic diversity of Clostridium botulinum Group III through extensive genome exploration. Front. Microbiol. 2016; 7(757):1-10.Carruthers J, Carruthers A, Dover JS, Alam M. Procedures in Cosmetic Dermatology. 4th ed. China: Elsevier; 2018.Nahai F, Lorenc P, Kenkel JM, Fagien S, Hirmand H, Nestor MS, Sclafani AP, Sykes JM, Waldorf HA. A review of AbobotulinumtoxinA (Dysport). Aesthetic Surgery Journal. 2013; 33(1):13-17.Datta Gupta A, Visvanathan R. Botulinum toxin for foot dystonia in patients with Parkinson’s disease having deep brain stimulation: a case series and a pilot study. J Rehabil Med. 2016;48(6):559-562.Kollewe K, Mohammadi B, Köller S, Pickenbrock H, Dengler R, Dressler D. Blepharospasm: long-term treatment with either Botox, Xeomin or Disport. J Neural Transm, Springer. 2015; 122(3):427-431.Rosow DE, Pechman A, Saint-Victor S, Lo K, Lundy DS, Casiano RR. Factors Influencing Botulinum Toxin Dose Instability in Spasmodic Dysphonia Patients. Journal of Voice. 2015; 29(3):352-355.Teemul TA, Patel R, Kanatas A, Carter LM. Management of oromandibular dystonia with botulinum A toxin: a series of cases. Br J Oral Maxillofac Surg, Science Direct. 2016; 54(10):1080-1084.Ababneh OH, Cetinkaya A, Kulwin DR. Long-term efficacy and safety of botulinum toxin A injections to treat blepharospasm and hemifacial spasm. Clinical and Experimental Ophtalmology. 2014; 42(3):254-261.Chan KH, Liang C, Wilson P, Higgins D, Allen GC. Long-term safety and efficacy data on botulinum toxin type A: an injection for sialorrhea. JAMA Otolaryngol Head Neck Surg. 2013; 139(2):134-138.Hooft N, Schmidt ES, Bremner RM. Achalasia in pregnancy: Botulinum toxin A injection of lower esophageal sphincter. Hindawi Publishing Corporation. 2015;():-.Dressler D, Tacik P, Adib Saberi F. Botulinum toxin therapy of cervical dystonia: comparing onabotulinumtoxinA (Botox®) and incobotulinumtoxinA (Xeomin®). J Neural Transm (Vienna). 2014; 121(1):29-31.Martínez-Ramírez D, Giugni JC, Hastings E, Wagle Shukla A, Malaty IA, Okun MS, Rodríguez RL. Comparable Botulinum Toxin Outcomes between Primary and Secondary Blepharospasm: A Retrospective Analysis. Tremor Other Hyperkinet Mov (N Y). 2014; 4(286):1-7.Pandey S, Sharma S. Botulinum toxin in Meige's syndrome: A video-based case series. Neurol India. 2018; 66(1):71-76.Ravindra P, Jackson BL, Parkinson RJ. Botulinum toxin type A for the treatment of non-neurogenic overactive bladder: does using onabotulinumtoxinA (Botox®) or abobotulinumtoxinA (Dysport®) make a difference?. BJU Int. 2013; 112(1):94-99.Merino PS, Vera RE, Mariñas LG, Gómez de Liaño PS, Escribano JV. Botulinum toxin for treatment of restrictive strabismus. Journal of Optometry. 2017; 10(3):189-193.Shafik Elridy A, Eldin Zaki RG, Fazwy Elshinawy R. Comparison of the Clinical Efficacy of Abobotulinumtoxin A (ABO) and Onabotulinumtoxin A (ONA) in the Treatment of Crow’s Feet Wrinkles: A Split-Face Study. Seminars in Ophthalmology. 2017; 33(2):1-9.Del Río Navarrete MP. Botulinum Toxin for Mentum and Perioral Area. En: Issa M, Tamura B, editores. Botulinum Toxins, Fillers and Related Substances. Clinical Approaches and Procedures in Cosmetic Dermatology. Alemania: Springer; 2017. p 1-10.Nahai F, Lorenc P, Kenkel JM, Fagien S, Hirmand H, Nestor M, Sclafani A, Sykes JM, Waldorf HA. IncobotulinumtoxinA in clinical literature. Aesthetic Surgery Journal. 2013; 33(1):23-34.Rostedt Punga A, Alimohammadi M, Fagrell D, Nyberg F, Rees D, Wong C. A Randomized, Comparative Study to Evaluate Efficacy and Safety of Two Injection Volumes of AbobotulinumtoxinA in Treatment of Glabellar Lines. Dermatol Surg. 2016; 42(8):967-976.Trindade de Almeida A, Carruthers J, Cox SE, Goldman M, Wheeler S, Gallagher C. Patient Satisfaction and Safety With Aesthetic OnabotulinumtoxinA After At Least 5 Years: A Retrospective Cross-Sectional Analysis of 4,402 Glabellar Treatments. Dermatologic Surgery. 2015; 41():S19-S28.Susmita A, Devi Kolli NN, Meka S, Chakravarthi SP, Kattimani VS, Lingamaneni KP, Shaik LS. An Evaluation of Use of Botulinum Toxin Type A in the Management of Dynamic Forehead Wrinkles - A Clinical Study. J Clin Diagn Res. 2016; 10(10):127-131.Robinson DM, Horne DF, Rohrer TE. Shaping of the Eyebrows with Botulinum Toxin Type A (BoNT-A). En: Hartstein ME, Massry G, Holds J, editores. Pearls and Pitfalls in Cosmetic Oculoplastic Surgery. Nueva York: Springer; 2015. p 413-415.ühne U, Imhof M. IncobotulinumtoxinA (Xeomin/Bocouture). En: Cohen J, Ozog D, editores. Botulinum toxins: Cosmetic and Clinical Applications. 1 st ed.: John Wiley & Sons Ltd.; 2017. p 79-95.Emer JJ, Axibal E, Marmur ES, Waldorf H. OnabotulinumtoxinA (Botox) in Dermatology. En: Cohen J, Ozog D, editors. Botulinum toxins: Cosmetic and Clinical Applications. 1 st ed.: John Wiley & Sons Ltd.; 2017. p 357-367.Jones D, Kerscher M, Geister T, Hast M, Weissenberger P. Efficacy of IncobotulinumtoxinA for the Treatment of Glabellar Frown Lines in Male Subjects: Post-Hoc Analyses From Randomized, Double-Blind Pivotal Studies. Dermatologic Surgery. 2017; 43():S235-S241.Ascher B, Kestemont P, Boineau D, Bodokh I, Stein A, Heckmann M, Dendorfer M, Pavicic T, Volteau M, Tse A, Picaut P, Rzany B. Liquid Formulation of AbobotulinumtoxinA Exhibits a Favorable Efficacy and Safety Profile in Moderate to Severe Glabellar Lines: A Randomized, Double-Blind, Placebo- and Active Comparator-Controlled Trial. Aesthetic Surgery Journal. 2018; 38(2):183-191.Nahai F, Lorenc P, Kenkel JM, Fagien S, Hirmand H, Nestor SM, Sclafani AP, Sykes JM, Waldorf HA. Incobotulinumtoxin A (Xeomin). Aesthetic Surgery Journal. 2013; 33(1):18-22.Pavicic T, Prager W, Klöppel M, Ravichandran S, Galatoire O. IncobotulinumtoxinA use in aesthetic indications in daily practice: a European multicenter, noninterventional, retrospective study. Clin Cosmet Investig Dermatol. 2015; 8():135-142.Streker M, Luebberding S, Krueger N, Harrington L, Kerscher M. Patient- Reported Outcomes After IncobotulinumtoxinA Treatment for Upper Facial Wrinkles. Dermatologic Surgery. 2015; 41():29-38.Gubanova E, Haddad Tabet M, Bergerova Y, Moiseieva O, Chemeris A, Sanches E, Sharova A, Rodríguez Pose L, Raymond R, Prygova I, Carlisle I. Assessment of Subject and Physician Satisfaction after Long-Term Treatment of Glabellar Lines with AbobotulinumtoxinA (Dysport®/Azzalure®): Primary Results of the APPEAL Noninterventional Study. Aesthetic Plastic Surgery. 2018; 42(6): 1672–1680.Wilson A, Chang B, Taglienti A, Chin B, Chang C, Folsom N, Percec I. A Quantitative Analysis of OnabotulinumtoxinA, AbobotulinumtoxinA, and IncobotulinumtoxinA: A Randomized, Double-Blind, Prospective Clinical Trial of Comparative Dynamic Strain Reduction. Plast Reconstr Surg. 2016; 137(5):1424-1433.Berkowitz D. Botox Nation. Changing the face of America. New York University Press. 2017.The International Study on Aesthetic/Cosmetic Procedures Performed in 2016 [Internet]. ISAPS International Society of Aesthetic Plastic Surgery. Disponible en: https://www.isaps.org/wp- content/uploads/2019/03/ISAPS_2017_International_Study_Cosmetic_Proc edures_NEW.pdfPlastic Surgery Statistics Report 2017 [Internet]. ASPS American Society of Plastic Surgeons. Disponible en: https://www.plasticsurgery.org/documents/News/Statistics/2018/plastic- surgery-statistics-report-2018.pdfPickett A. Botulinum Toxin as a Clinical Product: Manufacture and Pharmacology. En: Foster KA, editores. Clinical Applications of Botulinum Neurotoxin. Vol 5. EE.UU.: Springer; 2014. p 7-49.Garcia-Murray E, Velasco-Villasenor ML, Acevedo B, Luna S, Lee J, Waugh JM, Hornfeldt CS. Safety and efficacy of RT002, an injectable botulinum toxin type A, for treating glabellar lines: results of a phase 1/2, open-label, sequential dose- escalation study. Dermatol Surg. 2015; 41(Suppl 1):S47-S55.Paul Lorenc Z. Abstract: DWP-450, Purified Botulinum Toxin Type A, for the Treatment of Moderate-to-Severe Glabellar Lines in Adult Subjects: Results from Two Randomized, Double-Blind, Placebo-Controlled, Single Dose Phase III Safety and Efficacy Studies. Plast Reconstr Surg Glob Open. 2017; 5(9 Suppl):193-194.Carruthers J, Carruthers A. Treatment of glabellar frown lines with C. botulinum-A exotoxin. J Dermatol Surg Oncol. 1992; 18(1)17-21.Blitzer A, Brin MF, Keen MS, Aviv JE. Botulinum toxin for the treatment of hyperfunctional lines of the face. Arch Otolaryngol Head Neck Surg. 1993; 119(9):1018-1022.Blitzer A, Binder WJ, Aviv JE, Keen MS, Brin MF. The management of hyperfunctional facial lines with botulinum toxin. A collaborative study of 210 injection sites in 162 patients. Arch Otolaryngol Head Neck Surg. 1997; 123(4):389-392.Carruthers J, Carruthers A. Aesthetic botulinum A toxin in the mid and lower face and neck. Dermatol Surg. 2003; 29(5):468-476.Kim NH, Chung JH, Park RH, Park JB. The use of botulinum toxin type A in aesthetic mandibular contouring. Plast Reconstr Surg. 2005; 115(3):919-930.Ascher B, Talarico S, Cassuto D, Escobar S, Hexsel D, Jaén P, Monheit GD, Rzany B, Viel M. International consensus recommendations on the aesthetic usage of botulinum toxin type A (Speywood Unit)-Part I: Upper facial wrinkles. J Eur Acad Dermatol Venereol. 2010; 24(11):1278-1284.Dorizas A, Krueger N, Sadick NS. Aesthetic uses of the botulinum toxins. 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Unicolmayorrepositorio@unicolmayor.edu.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