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Wrinkle

A wrinkle, also known as a rhytid, is a fold, ridge or crease in an otherwise smooth surface, such as on skin or fabric. Skin wrinkles typically appear as a result of ageing processes such as glycation,[1] habitual sleeping positions,[2] loss of body mass, sun damage,[3] or temporarily, as the result of prolonged immersion in water. Age wrinkling in the skin is promoted by habitual facial expressions, aging, sun damage, smoking, poor hydration, and various other factors.[4] In humans, it can also be prevented to some degree by avoiding excessive solar exposure and through diet (in particular through consumption of carotenoids, tocopherols and flavonoids, vitamins (A, C, D and E), essential omega-3-fatty acids, certain proteins and lactobacilli).[5]

Skin edit

Causes for aging wrinkles edit

 
A woman of European origin with facial wrinkles

Development of facial wrinkles is a kind of fibrosis of the skin. Misrepair-accumulation aging theory suggests that wrinkles develop from incorrect repairs of injured elastic fibers and collagen fibers.[6][7][8] Repeated extensions and compressions of the skin cause repeated injuries of extracellular fibers in derma. During the repairing process, some of the broken elastic fibers and collagen fibers are not regenerated and restored but replaced by altered fibers. When an elastic fiber is broken in an extended state, it may be replaced by a "long" collagen fiber. Accumulation of "long" collagen fibers makes part of the skin looser and stiffer, and as a consequence, a big fold of skin appears. When a "long" collagen is broken in a compressed state, it may be replaced by a "short" collagen fiber. The "shorter" collagen fibers will restrict the extension of "longer" fibers, and make the “long" fibers in a folding state permanently. A small fold, namely a permanent wrinkle, then appears.

Sleep wrinkles edit

 
Wrinkles on the face and hands are a typical sign of aging

Sleep wrinkles are created and reinforced when the face is compressed against a pillow or bed surface in side or stomach sleeping positions during sleep.[9] They appear in predictable locations due to the underlying superficial musculoaponeurotic system (SMAS), and are usually distinct from wrinkles of facial expression.[10] As with wrinkles of facial expression, sleep wrinkles can deepen and become permanent over time, unless the habitual sleeping positions which cause the wrinkles are altered.[11]

Water-immersion wrinkling edit

 
A wrinkled finger after a warm bath

The wrinkles that occur in skin over prolonged exposure to water are sometimes referred to as pruney fingers or water aging. This is a temporary skin condition where the skin on the palms of the hand or feet becomes wrinkly. This wrinkling response may have imparted an evolutionary benefit by providing improved traction in wet conditions,[12] and a better grasp of wet objects.[13] These results were called into question by a 2014 study that failed to reproduce any improvement of handling wet objects with wrinkled fingertips.[14] However, a 2020 study of gripping efficiency found that wrinkles decreased the force required to grip wet objects by 20%, supporting the traction hypothesis.[15]

Prior to a 1935 study, the common explanation was based on water absorption in the keratin-laden epithelial skin when immersed in water,[16] causing the skin to expand and resulting in a larger surface area, forcing it to wrinkle. Usually the tips of the fingers and toes are the first to wrinkle because of a thicker layer of keratin and an absence of hairs which secrete the protective oil called sebum.

 
Adult sole showing water immersion wrinkling

In the 1935 study, however, Lewis and Pickering were studying patients with palsy of the median nerve when they discovered that skin wrinkling did not occur in the areas of the patients' skin normally innervated by the damaged nerve. This suggested that the nervous system plays an essential role in wrinkling, so the phenomenon could not be entirely explained simply by water absorption. Recent research shows that wrinkling is related to vasoconstriction.[17][18] Water probably initiates the wrinkling process by altering the balance of electrolytes in the skin as it diffuses into the hands and soles via their many sweat ducts. This could alter the stability of the membranes of the many neurons that synapse on the many blood vessels underneath skin, causing them to fire more rapidly. Increased neuronal firing causes blood vessels to constrict, decreasing the amount of fluid underneath the skin. This decrease in fluid would cause a decrease in tension, causing the skin to become wrinkly.[19]

This insight resulted in bedside tests for nerve damage and vasoconstriction. Wrinkling is often scored with immersion of the hands for 30 minutes in water or EMLA cream with measurements steps of 5 minutes, and counting the number of visible wrinkles in time. Not all healthy persons have finger wrinkling after immersion, so it would be safe to say that sympathetic function is preserved if finger wrinkling after immersion in water is observed, but if the fingers emerge smooth it cannot be assumed that there is a lesion to the autonomic supply or to the peripheral nerves of the hand.[20]

Animals with wrinkles edit

Examples of wrinkles can be found in various animal species that grow loose, excess skin, particularly when they are young. Several breeds of dog, such as the Pug and the Shar Pei, have been bred to exaggerate this trait. In dogs bred for fighting, this is the result of selection for loose skin, which confers a protective advantage.[21]

Techniques for reducing the appearance of aging wrinkles edit

 
A man receiving a botox injection

Current evidence suggests that tretinoin decreases cohesiveness of follicular epithelial cells, although the exact mode of action is unknown. Additionally, tretinoin stimulates mitotic activity and increased turnover of follicular epithelial cells.[22] Tretinoin is better known by the brand name Retin-A.

Topical glycosaminoglycans supplements can help to provide temporary restoration of enzyme balance to slow or prevent matrix breakdown and consequent onset of wrinkle formation. Glycosaminoglycans (GAGs) are produced by the body to maintain structural integrity in tissues and to maintain fluid balance. Hyaluronic acid is a type of GAG that promotes collagen synthesis, repair, and hydration. GAGs serve as a natural moisturizer and lubricant between epidermal cells to inhibit the production of matrix metalloproteinases (MMPs).

Dermal fillers are injectable products frequently used to correct wrinkles, and other depressions in the skin. They are often a kind of soft tissue designed to enable injection into the skin for purposes of improving the appearance. The most common products are based on hyaluronic acid and calcium hydroxylapatite.

Botulinum toxin is a neurotoxin protein produced by the bacterium Clostridium botulinum. Botox is a specific form of botulinum toxin manufactured by Allergan for both therapeutic and cosmetic use. Besides its cosmetic application, Botox is used in the treatment of other conditions including migraine headache and cervical dystonia (spasmodic torticollis) (a neuromuscular disorder involving the head and neck).[23]

Dysport, manufactured by Ipsen, received FDA approval and is now used to treat cervical dystonia as well as glabellar lines in adults. In 2010, another form of botulinum toxin, one free of complexing proteins, became available to Americans. Xeomin received FDA approval for medical indications in 2010 and cosmetic indications in 2011.

Botulinum toxin treats wrinkles by immobilizing the muscles which cause wrinkles. It is not appropriate for the treatment of all wrinkles; it is indicated for the treatment of glabellar lines (between the eyebrows) in adults. Any other usage is not approved by the FDA and is considered off-label use.

Laser resurfacing is FDA-cleared skin resurfacing procedure in which lasers are used to improve the condition of the skin.[citation needed] Two types of lasers are used to reduce the appearance of fine lines and wrinkles on the face; laser ablation, which removes thin layers of skin, and nonablative lasers that stimulate collagen production. Nonablative lasers are less effective than ablative ones but they are less invasive and recovery time is short. After the procedure people experience temporary redness, itching and swelling.

See also edit

References edit

  1. ^ Danby, FW (Jul–Aug 2010). "Nutrition and aging skin: sugar and glycation". Clin Dermatol. 4. 28 (4): 409–411. doi:10.1016/j.clindermatol.2010.03.018. PMID 20620757.
  2. ^ American Academy of Dermatology. "Causes of Aging". AgingSkinNet. American Academy of Dermatology. Retrieved 5 March 2013.
  3. ^ Cosmetic Procedures for Wrinkles
  4. ^ Anderson, Laurence. 2006. Looking Good, the Australian guide to skin care, cosmetic medicine and cosmetic surgery. AMPCo. Sydney. ISBN 0-85557-044-X.
  5. ^ Schagen, S. K.; Zampeli, V. A.; Makrantonaki, E.; Zouboulis, C. C. (2012). "Discovering the link between nutrition and skin aging". Dermato-Endocrinology. 4 (3): 298–307. doi:10.4161/derm.22876. PMC 3583891. PMID 23467449.
  6. ^ Wang, Jicun; Michelitsch, Thomas; Wunderlin, Arne; Mahadeva, Ravi (2009). "Aging as a consequence of Misrepair—a novel theory of aging". arXiv:0904.0575 [q-bio.TO].
  7. ^ Wang-Michelitsch, Jicun; Michelitsch, Thomas (2015). "Aging as a process of accumulation of Misrepairs". arXiv:1503.07163 [q-bio.TO].
  8. ^ Wang-Michelitsch, Jicun; Michelitsch, Thomas (2015). "Tissue fibrosis: a principal evidence for the central role of Misrepairs in aging". arXiv:1505.01376 [q-bio.TO].
  9. ^ Sarifakioglu, Nedim; Terzioglu, A.; Ates, L.; Aslan, G. (2004). "A New Phenomenon: 'Sleep Lines' on the Face". Scan J Plast Reconstr Surg Hand Surg. 38 (4): 244–247. doi:10.1080/02844310410027257. PMID 15370809. S2CID 25307487.
  10. ^ Fulton, James E.; Gaminchi, F. (1999). "Sleep Lines". Dermatol Surg. 25 (1): 59–62. doi:10.1046/j.1524-4725.1999.08073.x. PMID 9935097.
  11. ^ Sarifakioglu, Nedim; Terzioglu, A.; Ates, L.; Aslan, G. (2004). "A New Phenomenon: 'Sleep Lines' on the Face". Scan J Plast Reconstr Surg Hand Surg. 38 (4): 244–247 [246]. doi:10.1080/02844310410027257. PMID 15370809. S2CID 25307487.
  12. ^ Mark Changizi; Romann Weber; Ritesh Kotecha; Joseph Palazzo (2011). "Are Wet-Induced Wrinkled Fingers Primate Rain Treads?". Brain, Behavior and Evolution. 77 (4): 286–90. doi:10.1159/000328223. PMID 21701145.
  13. ^ Kareklas, Kyriacos; Nettle, Daniel; Smulders, Tom V (January 9, 2013). "Water-induced finger wrinkles improve handling of wet objects". Biol. Lett. 9 (2): 20120999. doi:10.1098/rsbl.2012.0999. PMC 3639753. PMID 23302867.
  14. ^ Haseleu, Julia; Omerbašić, Damir; Frenzel, Henning; Gross, Manfred; Lewin, Gary R. (2014). Goldreich, Daniel (ed.). "Water-Induced Finger Wrinkles Do Not Affect Touch Acuity or Dexterity in Handling Wet Objects". PLOS ONE. 9 (1): e84949. Bibcode:2014PLoSO...984949H. doi:10.1371/journal.pone.0084949. PMC 3885627. PMID 24416318.
  15. ^ Davis, N. (8 November 2020). "Water-immersion finger-wrinkling improves grip efficiency in handling wet objects". bioRxiv 10.1101/2020.11.07.372631.
  16. ^ "Dr Karl's Homework – Skin Wrinkles in Water (26/1/2000)". Abc.net.au. 2000-01-26. Retrieved 2019-04-30.
  17. ^ Einar P.V. Wilder-Smith; Adeline Chow (2003). "Water-immersion wrinkeling is due to vasoconstriction". Muscle & Nerve. 27 (3): 307–311. doi:10.1002/mus.10323. PMID 12635117. S2CID 45193684.
  18. ^ Einar P. V. Wilder-Smith (2004). "Water immersion wrinkling". Clinical Autonomic Research. 14 (2): 125–131. doi:10.1007/s10286-004-0172-4. PMID 15095056. S2CID 44938772.
  19. ^ H. Zhai, K.P. Whilem H. L. Maibach (2007). Dermatotoxicology. pp. 280–281.
  20. ^ G Alvarez, J Eurolo; P Canales (1980). "Finger wrinkling after immersion in water". British Medical Journal. 281 (6240): 586–587. doi:10.1136/bmj.281.6240.586-a. PMC 1713922. PMID 7427379.
  21. ^ The Dog Encyclopedia: The Definitive Visual Guide. Penguin. 15 August 2023. p. 84. ISBN 978-0-7440-8513-6.
  22. ^ Stefanaki C, Stratigos A, Katsambas A (June 2005). "Topical retinoids in the treatment of photoaging". J Cosmet Dermatol. 4 (2): 130–4. doi:10.1111/j.1473-2165.2005.40215.x. PMID 17166212. S2CID 44702740.
  23. ^ Brin MF, Lew MF, Adler CH, Comella CL, Factor SA, Jankovic J, O'Brien C, Murray JJ, Wallace JD, Willmer-Hulme A, Koller M (1999). "Safety and efficacy of NeuroBloc (botulinum toxin type B) in type A-resistant cervical dystonia". Neurology. 53 (7): 1431–8. doi:10.1212/WNL.53.7.1431. PMID 10534247.

External links edit

wrinkle, redirects, here, other, uses, disambiguation, writer, filmmaker, margaret, wrinkle, also, known, rhytid, fold, ridge, crease, otherwise, smooth, surface, such, skin, fabric, skin, wrinkles, typically, appear, result, ageing, processes, such, glycation. Wrinkles redirects here For other uses see Wrinkles disambiguation For the writer and filmmaker see Margaret Wrinkle A wrinkle also known as a rhytid is a fold ridge or crease in an otherwise smooth surface such as on skin or fabric Skin wrinkles typically appear as a result of ageing processes such as glycation 1 habitual sleeping positions 2 loss of body mass sun damage 3 or temporarily as the result of prolonged immersion in water Age wrinkling in the skin is promoted by habitual facial expressions aging sun damage smoking poor hydration and various other factors 4 In humans it can also be prevented to some degree by avoiding excessive solar exposure and through diet in particular through consumption of carotenoids tocopherols and flavonoids vitamins A C D and E essential omega 3 fatty acids certain proteins and lactobacilli 5 Contents 1 Skin 1 1 Causes for aging wrinkles 1 2 Sleep wrinkles 1 3 Water immersion wrinkling 1 4 Animals with wrinkles 1 5 Techniques for reducing the appearance of aging wrinkles 2 See also 3 References 4 External linksSkin editMain article Skin fold Causes for aging wrinkles edit nbsp A woman of European origin with facial wrinklesDevelopment of facial wrinkles is a kind of fibrosis of the skin Misrepair accumulation aging theory suggests that wrinkles develop from incorrect repairs of injured elastic fibers and collagen fibers 6 7 8 Repeated extensions and compressions of the skin cause repeated injuries of extracellular fibers in derma During the repairing process some of the broken elastic fibers and collagen fibers are not regenerated and restored but replaced by altered fibers When an elastic fiber is broken in an extended state it may be replaced by a long collagen fiber Accumulation of long collagen fibers makes part of the skin looser and stiffer and as a consequence a big fold of skin appears When a long collagen is broken in a compressed state it may be replaced by a short collagen fiber The shorter collagen fibers will restrict the extension of longer fibers and make the long fibers in a folding state permanently A small fold namely a permanent wrinkle then appears Sleep wrinkles edit nbsp Wrinkles on the face and hands are a typical sign of agingSleep wrinkles are created and reinforced when the face is compressed against a pillow or bed surface in side or stomach sleeping positions during sleep 9 They appear in predictable locations due to the underlying superficial musculoaponeurotic system SMAS and are usually distinct from wrinkles of facial expression 10 As with wrinkles of facial expression sleep wrinkles can deepen and become permanent over time unless the habitual sleeping positions which cause the wrinkles are altered 11 Water immersion wrinkling edit nbsp A wrinkled finger after a warm bathThe wrinkles that occur in skin over prolonged exposure to water are sometimes referred to as pruney fingers or water aging This is a temporary skin condition where the skin on the palms of the hand or feet becomes wrinkly This wrinkling response may have imparted an evolutionary benefit by providing improved traction in wet conditions 12 and a better grasp of wet objects 13 These results were called into question by a 2014 study that failed to reproduce any improvement of handling wet objects with wrinkled fingertips 14 However a 2020 study of gripping efficiency found that wrinkles decreased the force required to grip wet objects by 20 supporting the traction hypothesis 15 Prior to a 1935 study the common explanation was based on water absorption in the keratin laden epithelial skin when immersed in water 16 causing the skin to expand and resulting in a larger surface area forcing it to wrinkle Usually the tips of the fingers and toes are the first to wrinkle because of a thicker layer of keratin and an absence of hairs which secrete the protective oil called sebum nbsp Adult sole showing water immersion wrinklingIn the 1935 study however Lewis and Pickering were studying patients with palsy of the median nerve when they discovered that skin wrinkling did not occur in the areas of the patients skin normally innervated by the damaged nerve This suggested that the nervous system plays an essential role in wrinkling so the phenomenon could not be entirely explained simply by water absorption Recent research shows that wrinkling is related to vasoconstriction 17 18 Water probably initiates the wrinkling process by altering the balance of electrolytes in the skin as it diffuses into the hands and soles via their many sweat ducts This could alter the stability of the membranes of the many neurons that synapse on the many blood vessels underneath skin causing them to fire more rapidly Increased neuronal firing causes blood vessels to constrict decreasing the amount of fluid underneath the skin This decrease in fluid would cause a decrease in tension causing the skin to become wrinkly 19 This insight resulted in bedside tests for nerve damage and vasoconstriction Wrinkling is often scored with immersion of the hands for 30 minutes in water or EMLA cream with measurements steps of 5 minutes and counting the number of visible wrinkles in time Not all healthy persons have finger wrinkling after immersion so it would be safe to say that sympathetic function is preserved if finger wrinkling after immersion in water is observed but if the fingers emerge smooth it cannot be assumed that there is a lesion to the autonomic supply or to the peripheral nerves of the hand 20 Animals with wrinkles edit Examples of wrinkles can be found in various animal species that grow loose excess skin particularly when they are young Several breeds of dog such as the Pug and the Shar Pei have been bred to exaggerate this trait In dogs bred for fighting this is the result of selection for loose skin which confers a protective advantage 21 Techniques for reducing the appearance of aging wrinkles edit nbsp A man receiving a botox injectionCurrent evidence suggests that tretinoin decreases cohesiveness of follicular epithelial cells although the exact mode of action is unknown Additionally tretinoin stimulates mitotic activity and increased turnover of follicular epithelial cells 22 Tretinoin is better known by the brand name Retin A Topical glycosaminoglycans supplements can help to provide temporary restoration of enzyme balance to slow or prevent matrix breakdown and consequent onset of wrinkle formation Glycosaminoglycans GAGs are produced by the body to maintain structural integrity in tissues and to maintain fluid balance Hyaluronic acid is a type of GAG that promotes collagen synthesis repair and hydration GAGs serve as a natural moisturizer and lubricant between epidermal cells to inhibit the production of matrix metalloproteinases MMPs Dermal fillers are injectable products frequently used to correct wrinkles and other depressions in the skin They are often a kind of soft tissue designed to enable injection into the skin for purposes of improving the appearance The most common products are based on hyaluronic acid and calcium hydroxylapatite Botulinum toxin is a neurotoxin protein produced by the bacterium Clostridium botulinum Botox is a specific form of botulinum toxin manufactured by Allergan for both therapeutic and cosmetic use Besides its cosmetic application Botox is used in the treatment of other conditions including migraine headache and cervical dystonia spasmodic torticollis a neuromuscular disorder involving the head and neck 23 Dysport manufactured by Ipsen received FDA approval and is now used to treat cervical dystonia as well as glabellar lines in adults In 2010 another form of botulinum toxin one free of complexing proteins became available to Americans Xeomin received FDA approval for medical indications in 2010 and cosmetic indications in 2011 Botulinum toxin treats wrinkles by immobilizing the muscles which cause wrinkles It is not appropriate for the treatment of all wrinkles it is indicated for the treatment of glabellar lines between the eyebrows in adults Any other usage is not approved by the FDA and is considered off label use Laser resurfacing is FDA cleared skin resurfacing procedure in which lasers are used to improve the condition of the skin citation needed Two types of lasers are used to reduce the appearance of fine lines and wrinkles on the face laser ablation which removes thin layers of skin and nonablative lasers that stimulate collagen production Nonablative lasers are less effective than ablative ones but they are less invasive and recovery time is short After the procedure people experience temporary redness itching and swelling See also editBotulinum toxin Injectable filler Wrinkly skin syndromeReferences edit Danby FW Jul Aug 2010 Nutrition and aging skin sugar and glycation Clin Dermatol 4 28 4 409 411 doi 10 1016 j clindermatol 2010 03 018 PMID 20620757 American Academy of Dermatology Causes of Aging AgingSkinNet American Academy of Dermatology Retrieved 5 March 2013 Cosmetic Procedures for Wrinkles Anderson Laurence 2006 Looking Good the Australian guide to skin care cosmetic medicine and cosmetic surgery AMPCo Sydney ISBN 0 85557 044 X Schagen S K Zampeli V A Makrantonaki E Zouboulis C C 2012 Discovering the link between nutrition and skin aging Dermato Endocrinology 4 3 298 307 doi 10 4161 derm 22876 PMC 3583891 PMID 23467449 Wang Jicun Michelitsch Thomas Wunderlin Arne Mahadeva Ravi 2009 Aging as a consequence of Misrepair a novel theory of aging arXiv 0904 0575 q bio TO Wang Michelitsch Jicun Michelitsch Thomas 2015 Aging as a process of accumulation of Misrepairs arXiv 1503 07163 q bio TO Wang Michelitsch Jicun Michelitsch Thomas 2015 Tissue fibrosis a principal evidence for the central role of Misrepairs in aging arXiv 1505 01376 q bio TO Sarifakioglu Nedim Terzioglu A Ates L Aslan G 2004 A New Phenomenon Sleep Lines on the Face Scan J Plast Reconstr Surg Hand Surg 38 4 244 247 doi 10 1080 02844310410027257 PMID 15370809 S2CID 25307487 Fulton James E Gaminchi F 1999 Sleep Lines Dermatol Surg 25 1 59 62 doi 10 1046 j 1524 4725 1999 08073 x PMID 9935097 Sarifakioglu Nedim Terzioglu A Ates L Aslan G 2004 A New Phenomenon Sleep Lines on the Face Scan J Plast Reconstr Surg Hand Surg 38 4 244 247 246 doi 10 1080 02844310410027257 PMID 15370809 S2CID 25307487 Mark Changizi Romann Weber Ritesh Kotecha Joseph Palazzo 2011 Are Wet Induced Wrinkled Fingers Primate Rain Treads Brain Behavior and Evolution 77 4 286 90 doi 10 1159 000328223 PMID 21701145 Kareklas Kyriacos Nettle Daniel Smulders Tom V January 9 2013 Water induced finger wrinkles improve handling of wet objects Biol Lett 9 2 20120999 doi 10 1098 rsbl 2012 0999 PMC 3639753 PMID 23302867 Haseleu Julia Omerbasic Damir Frenzel Henning Gross Manfred Lewin Gary R 2014 Goldreich Daniel ed Water Induced Finger Wrinkles Do Not Affect Touch Acuity or Dexterity in Handling Wet Objects PLOS ONE 9 1 e84949 Bibcode 2014PLoSO 984949H doi 10 1371 journal pone 0084949 PMC 3885627 PMID 24416318 Davis N 8 November 2020 Water immersion finger wrinkling improves grip efficiency in handling wet objects bioRxiv 10 1101 2020 11 07 372631 Dr Karl s Homework Skin Wrinkles in Water 26 1 2000 Abc net au 2000 01 26 Retrieved 2019 04 30 Einar P V Wilder Smith Adeline Chow 2003 Water immersion wrinkeling is due to vasoconstriction Muscle amp Nerve 27 3 307 311 doi 10 1002 mus 10323 PMID 12635117 S2CID 45193684 Einar P V Wilder Smith 2004 Water immersion wrinkling Clinical Autonomic Research 14 2 125 131 doi 10 1007 s10286 004 0172 4 PMID 15095056 S2CID 44938772 H Zhai K P Whilem H L Maibach 2007 Dermatotoxicology pp 280 281 G Alvarez J Eurolo P Canales 1980 Finger wrinkling after immersion in water British Medical Journal 281 6240 586 587 doi 10 1136 bmj 281 6240 586 a PMC 1713922 PMID 7427379 The Dog Encyclopedia The Definitive Visual Guide Penguin 15 August 2023 p 84 ISBN 978 0 7440 8513 6 Stefanaki C Stratigos A Katsambas A June 2005 Topical retinoids in the treatment of photoaging J Cosmet Dermatol 4 2 130 4 doi 10 1111 j 1473 2165 2005 40215 x PMID 17166212 S2CID 44702740 Brin MF Lew MF Adler CH Comella CL Factor SA Jankovic J O Brien C Murray JJ Wallace JD Willmer Hulme A Koller M 1999 Safety and efficacy of NeuroBloc botulinum toxin type B in type A resistant cervical dystonia Neurology 53 7 1431 8 doi 10 1212 WNL 53 7 1431 PMID 10534247 External links edit nbsp Look up wrinkle in Wiktionary the free dictionary nbsp Wikimedia Commons has media related to Wrinkles skin Skin Ageing at Medline Retrieved from https en wikipedia org w index php title Wrinkle amp oldid 1187678726, wikipedia, wiki, book, books, library,

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