Indole-3-acetic acid: A potential new photosensitizer for photodynamic therapy of acne vulgaris
Background and Objectives ALA (5‐aminolevulinic acid) photodynamic therapy (PDT) is a new treatment option for acne. However, it needs a relatively long incubation period and adverse effects are common. Indole‐3‐acetic acid (IAA) is not toxic by itself but produces free radicals with ultraviolet B....
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| Veröffentlicht in: | Lasers in surgery and medicine 2011-03, Vol.43 (3), p.200-205 |
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| creator | Na, Jung-Im Kim, So-Young Kim, Jeong-Hye Youn, Sang-Woong Huh, Chang-Hun Park, Kyoung-Chan |
| description | Background and Objectives
ALA (5‐aminolevulinic acid) photodynamic therapy (PDT) is a new treatment option for acne. However, it needs a relatively long incubation period and adverse effects are common. Indole‐3‐acetic acid (IAA) is not toxic by itself but produces free radicals with ultraviolet B. In this study we examined the potential of IAA as a photosensitizer for acne treatment.
Materials and Methods
Free radical formation was measured after visible light irradiation of IAA. Antimicrobial effect was evaluated by assessing growth suppression of Propionibacterium acnes and Staphylococcus aureus after IAA PDT. To evaluate the histological changes, skin biopsies were performed on nude mice skin after IAA PDT. To evaluate the clinical efficacy of IAA PDT, 14 acne patients were treated with the following IAA PDT regimen: three times each with a 15 minutes incubation period and a 2‐week interval. The number of inflammatory lesions and the amount of sebum secretion were then assessed.
Results
IAA produced free radicals with green light irradiation. Importantly, IAA lost its photosensitizing ability after exposure to certain amount of light. This implies IAA PDT would not require post‐procedure photo‐protection. The growth of P. acnes and S. aureus were significantly suppressed with IAA PDT. In addition, IAA PDT treated skin showed destruction of follicular ostia epithelium. Interestingly, there was no significant difference between a 4 hours and a 30 minutes incubation, which means that longer absorption time is not necessary for IAA PDT. In the clinical study, inflammatory lesions and sebum secretion were significantly reduced. The procedure was painless and no adverse effect was observed. Photo‐protection was not performed and there were no further phototoxic responses.
Conclusions
IAA PDT has therapeutic effects on acne via its antimicrobial activities, its sebum‐reducing effect and through relieving follicular occlusion. It is a very simple and safe treatment option for acne. Lasers Surg. Med. 43:200–205, 2011. © 2011 Wiley‐Liss, Inc. |
| doi_str_mv | 10.1002/lsm.21029 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_857811526</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>857811526</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3959-b93e61a5a66c8a24ecf6a75443cbda6ff3f4ab9221c0857eeef579317a3a39873</originalsourceid><addsrcrecordid>eNp9kE9T1TAURzOOjjzQhV-A6U5ZFPKnTRp3DKPA8NQFKu4y96U3EGibmvSJz09PsMBOV7mTOb-zOIS8YXSfUcoPutTvc0a5fkYWjGpZakbZc7KgLN8N1XyLbKd0TSkVnKqXZIuzivGGigUxp0MbOixFCRYnbwuwvn1fHBZjmHCYPHTFgLfFeBWmkHBIfvJ_MBYuxPmv3QzQ59l0hRHGTRFcNgxY_Fp3lxB9ekVeOOgSvn54d8i3jx--Hp2Uyy_Hp0eHy9IKXetypQVKBjVIaRvgFVonQdVVJeyqBemccBWsNOfM0qZWiOhqpQVTIEDoRokd8nb2jjH8XGOaTO-Txa6DAcM6mTxqGKu5zOS7_5I5ndKSZndG92bUxpBSRGfG6HuImwyZ-_Imlzd_y2d290G7XvXYPpGPqTNwMAO3vsPNv01mef7pUVnOC58m_P20gHhjpBKqNhefj8352QWtv6sfhok7vCGceQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1017960317</pqid></control><display><type>article</type><title>Indole-3-acetic acid: A potential new photosensitizer for photodynamic therapy of acne vulgaris</title><source>MEDLINE</source><source>Wiley Online Library All Journals</source><creator>Na, Jung-Im ; Kim, So-Young ; Kim, Jeong-Hye ; Youn, Sang-Woong ; Huh, Chang-Hun ; Park, Kyoung-Chan</creator><creatorcontrib>Na, Jung-Im ; Kim, So-Young ; Kim, Jeong-Hye ; Youn, Sang-Woong ; Huh, Chang-Hun ; Park, Kyoung-Chan</creatorcontrib><description>Background and Objectives
ALA (5‐aminolevulinic acid) photodynamic therapy (PDT) is a new treatment option for acne. However, it needs a relatively long incubation period and adverse effects are common. Indole‐3‐acetic acid (IAA) is not toxic by itself but produces free radicals with ultraviolet B. In this study we examined the potential of IAA as a photosensitizer for acne treatment.
Materials and Methods
Free radical formation was measured after visible light irradiation of IAA. Antimicrobial effect was evaluated by assessing growth suppression of Propionibacterium acnes and Staphylococcus aureus after IAA PDT. To evaluate the histological changes, skin biopsies were performed on nude mice skin after IAA PDT. To evaluate the clinical efficacy of IAA PDT, 14 acne patients were treated with the following IAA PDT regimen: three times each with a 15 minutes incubation period and a 2‐week interval. The number of inflammatory lesions and the amount of sebum secretion were then assessed.
Results
IAA produced free radicals with green light irradiation. Importantly, IAA lost its photosensitizing ability after exposure to certain amount of light. This implies IAA PDT would not require post‐procedure photo‐protection. The growth of P. acnes and S. aureus were significantly suppressed with IAA PDT. In addition, IAA PDT treated skin showed destruction of follicular ostia epithelium. Interestingly, there was no significant difference between a 4 hours and a 30 minutes incubation, which means that longer absorption time is not necessary for IAA PDT. In the clinical study, inflammatory lesions and sebum secretion were significantly reduced. The procedure was painless and no adverse effect was observed. Photo‐protection was not performed and there were no further phototoxic responses.
Conclusions
IAA PDT has therapeutic effects on acne via its antimicrobial activities, its sebum‐reducing effect and through relieving follicular occlusion. It is a very simple and safe treatment option for acne. Lasers Surg. Med. 43:200–205, 2011. © 2011 Wiley‐Liss, Inc.</description><identifier>ISSN: 0196-8092</identifier><identifier>ISSN: 1096-9101</identifier><identifier>EISSN: 1096-9101</identifier><identifier>DOI: 10.1002/lsm.21029</identifier><identifier>PMID: 21412803</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>5-aminolevulinic acid ; Acne ; Acne Vulgaris - drug therapy ; Acne Vulgaris - microbiology ; Acne Vulgaris - pathology ; Animals ; Antimicrobial activity ; Antimicrobial agents ; Biopsy ; Dose-Response Relationship, Drug ; Double-Blind Method ; Drug Administration Schedule ; Epithelial Cells - drug effects ; Epithelial Cells - pathology ; Epithelium ; Free radicals ; Free Radicals - metabolism ; Hair Follicle - drug effects ; Hair Follicle - pathology ; Humans ; indole-3-acetic acid ; Indoleacetic Acids - administration & dosage ; Indoleacetic Acids - chemistry ; Indoleacetic Acids - pharmacology ; Indoleacetic Acids - therapeutic use ; Inflammation ; Lasers ; Light effects ; Male ; Mice ; Occlusion ; Photochemotherapy ; photodynamic therapy ; Photosensitization ; Photosensitizing Agents - administration & dosage ; Photosensitizing Agents - chemistry ; Photosensitizing Agents - pharmacology ; Photosensitizing Agents - therapeutic use ; Pilot Projects ; Propionibacterium acnes ; Propionibacterium acnes - drug effects ; Sebaceous Glands - drug effects ; Sebaceous Glands - pathology ; Sebaceous Glands - secretion ; Sebum - secretion ; Secretion ; Side effects ; Skin ; Staphylococcus aureus ; Staphylococcus aureus - drug effects ; Treatment Outcome ; U.V. radiation</subject><ispartof>Lasers in surgery and medicine, 2011-03, Vol.43 (3), p.200-205</ispartof><rights>Copyright © 2011 Wiley‐Liss, Inc.</rights><rights>Copyright © 2011 Wiley-Liss, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3959-b93e61a5a66c8a24ecf6a75443cbda6ff3f4ab9221c0857eeef579317a3a39873</citedby><cites>FETCH-LOGICAL-c3959-b93e61a5a66c8a24ecf6a75443cbda6ff3f4ab9221c0857eeef579317a3a39873</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Flsm.21029$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Flsm.21029$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,781,785,1418,27929,27930,45579,45580</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21412803$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Na, Jung-Im</creatorcontrib><creatorcontrib>Kim, So-Young</creatorcontrib><creatorcontrib>Kim, Jeong-Hye</creatorcontrib><creatorcontrib>Youn, Sang-Woong</creatorcontrib><creatorcontrib>Huh, Chang-Hun</creatorcontrib><creatorcontrib>Park, Kyoung-Chan</creatorcontrib><title>Indole-3-acetic acid: A potential new photosensitizer for photodynamic therapy of acne vulgaris</title><title>Lasers in surgery and medicine</title><addtitle>Lasers Surg. Med</addtitle><description>Background and Objectives
ALA (5‐aminolevulinic acid) photodynamic therapy (PDT) is a new treatment option for acne. However, it needs a relatively long incubation period and adverse effects are common. Indole‐3‐acetic acid (IAA) is not toxic by itself but produces free radicals with ultraviolet B. In this study we examined the potential of IAA as a photosensitizer for acne treatment.
Materials and Methods
Free radical formation was measured after visible light irradiation of IAA. Antimicrobial effect was evaluated by assessing growth suppression of Propionibacterium acnes and Staphylococcus aureus after IAA PDT. To evaluate the histological changes, skin biopsies were performed on nude mice skin after IAA PDT. To evaluate the clinical efficacy of IAA PDT, 14 acne patients were treated with the following IAA PDT regimen: three times each with a 15 minutes incubation period and a 2‐week interval. The number of inflammatory lesions and the amount of sebum secretion were then assessed.
Results
IAA produced free radicals with green light irradiation. Importantly, IAA lost its photosensitizing ability after exposure to certain amount of light. This implies IAA PDT would not require post‐procedure photo‐protection. The growth of P. acnes and S. aureus were significantly suppressed with IAA PDT. In addition, IAA PDT treated skin showed destruction of follicular ostia epithelium. Interestingly, there was no significant difference between a 4 hours and a 30 minutes incubation, which means that longer absorption time is not necessary for IAA PDT. In the clinical study, inflammatory lesions and sebum secretion were significantly reduced. The procedure was painless and no adverse effect was observed. Photo‐protection was not performed and there were no further phototoxic responses.
Conclusions
IAA PDT has therapeutic effects on acne via its antimicrobial activities, its sebum‐reducing effect and through relieving follicular occlusion. It is a very simple and safe treatment option for acne. Lasers Surg. Med. 43:200–205, 2011. © 2011 Wiley‐Liss, Inc.</description><subject>5-aminolevulinic acid</subject><subject>Acne</subject><subject>Acne Vulgaris - drug therapy</subject><subject>Acne Vulgaris - microbiology</subject><subject>Acne Vulgaris - pathology</subject><subject>Animals</subject><subject>Antimicrobial activity</subject><subject>Antimicrobial agents</subject><subject>Biopsy</subject><subject>Dose-Response Relationship, Drug</subject><subject>Double-Blind Method</subject><subject>Drug Administration Schedule</subject><subject>Epithelial Cells - drug effects</subject><subject>Epithelial Cells - pathology</subject><subject>Epithelium</subject><subject>Free radicals</subject><subject>Free Radicals - metabolism</subject><subject>Hair Follicle - drug effects</subject><subject>Hair Follicle - pathology</subject><subject>Humans</subject><subject>indole-3-acetic acid</subject><subject>Indoleacetic Acids - administration & dosage</subject><subject>Indoleacetic Acids - chemistry</subject><subject>Indoleacetic Acids - pharmacology</subject><subject>Indoleacetic Acids - therapeutic use</subject><subject>Inflammation</subject><subject>Lasers</subject><subject>Light effects</subject><subject>Male</subject><subject>Mice</subject><subject>Occlusion</subject><subject>Photochemotherapy</subject><subject>photodynamic therapy</subject><subject>Photosensitization</subject><subject>Photosensitizing Agents - administration & dosage</subject><subject>Photosensitizing Agents - chemistry</subject><subject>Photosensitizing Agents - pharmacology</subject><subject>Photosensitizing Agents - therapeutic use</subject><subject>Pilot Projects</subject><subject>Propionibacterium acnes</subject><subject>Propionibacterium acnes - drug effects</subject><subject>Sebaceous Glands - drug effects</subject><subject>Sebaceous Glands - pathology</subject><subject>Sebaceous Glands - secretion</subject><subject>Sebum - secretion</subject><subject>Secretion</subject><subject>Side effects</subject><subject>Skin</subject><subject>Staphylococcus aureus</subject><subject>Staphylococcus aureus - drug effects</subject><subject>Treatment Outcome</subject><subject>U.V. radiation</subject><issn>0196-8092</issn><issn>1096-9101</issn><issn>1096-9101</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE9T1TAURzOOjjzQhV-A6U5ZFPKnTRp3DKPA8NQFKu4y96U3EGibmvSJz09PsMBOV7mTOb-zOIS8YXSfUcoPutTvc0a5fkYWjGpZakbZc7KgLN8N1XyLbKd0TSkVnKqXZIuzivGGigUxp0MbOixFCRYnbwuwvn1fHBZjmHCYPHTFgLfFeBWmkHBIfvJ_MBYuxPmv3QzQ59l0hRHGTRFcNgxY_Fp3lxB9ekVeOOgSvn54d8i3jx--Hp2Uyy_Hp0eHy9IKXetypQVKBjVIaRvgFVonQdVVJeyqBemccBWsNOfM0qZWiOhqpQVTIEDoRokd8nb2jjH8XGOaTO-Txa6DAcM6mTxqGKu5zOS7_5I5ndKSZndG92bUxpBSRGfG6HuImwyZ-_Imlzd_y2d290G7XvXYPpGPqTNwMAO3vsPNv01mef7pUVnOC58m_P20gHhjpBKqNhefj8352QWtv6sfhok7vCGceQ</recordid><startdate>201103</startdate><enddate>201103</enddate><creator>Na, Jung-Im</creator><creator>Kim, So-Young</creator><creator>Kim, Jeong-Hye</creator><creator>Youn, Sang-Woong</creator><creator>Huh, Chang-Hun</creator><creator>Park, Kyoung-Chan</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>201103</creationdate><title>Indole-3-acetic acid: A potential new photosensitizer for photodynamic therapy of acne vulgaris</title><author>Na, Jung-Im ; Kim, So-Young ; Kim, Jeong-Hye ; Youn, Sang-Woong ; Huh, Chang-Hun ; Park, Kyoung-Chan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3959-b93e61a5a66c8a24ecf6a75443cbda6ff3f4ab9221c0857eeef579317a3a39873</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>5-aminolevulinic acid</topic><topic>Acne</topic><topic>Acne Vulgaris - drug therapy</topic><topic>Acne Vulgaris - microbiology</topic><topic>Acne Vulgaris - pathology</topic><topic>Animals</topic><topic>Antimicrobial activity</topic><topic>Antimicrobial agents</topic><topic>Biopsy</topic><topic>Dose-Response Relationship, Drug</topic><topic>Double-Blind Method</topic><topic>Drug Administration Schedule</topic><topic>Epithelial Cells - drug effects</topic><topic>Epithelial Cells - pathology</topic><topic>Epithelium</topic><topic>Free radicals</topic><topic>Free Radicals - metabolism</topic><topic>Hair Follicle - drug effects</topic><topic>Hair Follicle - pathology</topic><topic>Humans</topic><topic>indole-3-acetic acid</topic><topic>Indoleacetic Acids - administration & dosage</topic><topic>Indoleacetic Acids - chemistry</topic><topic>Indoleacetic Acids - pharmacology</topic><topic>Indoleacetic Acids - therapeutic use</topic><topic>Inflammation</topic><topic>Lasers</topic><topic>Light effects</topic><topic>Male</topic><topic>Mice</topic><topic>Occlusion</topic><topic>Photochemotherapy</topic><topic>photodynamic therapy</topic><topic>Photosensitization</topic><topic>Photosensitizing Agents - administration & dosage</topic><topic>Photosensitizing Agents - chemistry</topic><topic>Photosensitizing Agents - pharmacology</topic><topic>Photosensitizing Agents - therapeutic use</topic><topic>Pilot Projects</topic><topic>Propionibacterium acnes</topic><topic>Propionibacterium acnes - drug effects</topic><topic>Sebaceous Glands - drug effects</topic><topic>Sebaceous Glands - pathology</topic><topic>Sebaceous Glands - secretion</topic><topic>Sebum - secretion</topic><topic>Secretion</topic><topic>Side effects</topic><topic>Skin</topic><topic>Staphylococcus aureus</topic><topic>Staphylococcus aureus - drug effects</topic><topic>Treatment Outcome</topic><topic>U.V. radiation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Na, Jung-Im</creatorcontrib><creatorcontrib>Kim, So-Young</creatorcontrib><creatorcontrib>Kim, Jeong-Hye</creatorcontrib><creatorcontrib>Youn, Sang-Woong</creatorcontrib><creatorcontrib>Huh, Chang-Hun</creatorcontrib><creatorcontrib>Park, Kyoung-Chan</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Lasers in surgery and medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Na, Jung-Im</au><au>Kim, So-Young</au><au>Kim, Jeong-Hye</au><au>Youn, Sang-Woong</au><au>Huh, Chang-Hun</au><au>Park, Kyoung-Chan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Indole-3-acetic acid: A potential new photosensitizer for photodynamic therapy of acne vulgaris</atitle><jtitle>Lasers in surgery and medicine</jtitle><addtitle>Lasers Surg. Med</addtitle><date>2011-03</date><risdate>2011</risdate><volume>43</volume><issue>3</issue><spage>200</spage><epage>205</epage><pages>200-205</pages><issn>0196-8092</issn><issn>1096-9101</issn><eissn>1096-9101</eissn><abstract>Background and Objectives
ALA (5‐aminolevulinic acid) photodynamic therapy (PDT) is a new treatment option for acne. However, it needs a relatively long incubation period and adverse effects are common. Indole‐3‐acetic acid (IAA) is not toxic by itself but produces free radicals with ultraviolet B. In this study we examined the potential of IAA as a photosensitizer for acne treatment.
Materials and Methods
Free radical formation was measured after visible light irradiation of IAA. Antimicrobial effect was evaluated by assessing growth suppression of Propionibacterium acnes and Staphylococcus aureus after IAA PDT. To evaluate the histological changes, skin biopsies were performed on nude mice skin after IAA PDT. To evaluate the clinical efficacy of IAA PDT, 14 acne patients were treated with the following IAA PDT regimen: three times each with a 15 minutes incubation period and a 2‐week interval. The number of inflammatory lesions and the amount of sebum secretion were then assessed.
Results
IAA produced free radicals with green light irradiation. Importantly, IAA lost its photosensitizing ability after exposure to certain amount of light. This implies IAA PDT would not require post‐procedure photo‐protection. The growth of P. acnes and S. aureus were significantly suppressed with IAA PDT. In addition, IAA PDT treated skin showed destruction of follicular ostia epithelium. Interestingly, there was no significant difference between a 4 hours and a 30 minutes incubation, which means that longer absorption time is not necessary for IAA PDT. In the clinical study, inflammatory lesions and sebum secretion were significantly reduced. The procedure was painless and no adverse effect was observed. Photo‐protection was not performed and there were no further phototoxic responses.
Conclusions
IAA PDT has therapeutic effects on acne via its antimicrobial activities, its sebum‐reducing effect and through relieving follicular occlusion. It is a very simple and safe treatment option for acne. Lasers Surg. Med. 43:200–205, 2011. © 2011 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>21412803</pmid><doi>10.1002/lsm.21029</doi><tpages>6</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Lasers in surgery and medicine, 2011-03, Vol.43 (3), p.200-205 |
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| subjects | 5-aminolevulinic acid Acne Acne Vulgaris - drug therapy Acne Vulgaris - microbiology Acne Vulgaris - pathology Animals Antimicrobial activity Antimicrobial agents Biopsy Dose-Response Relationship, Drug Double-Blind Method Drug Administration Schedule Epithelial Cells - drug effects Epithelial Cells - pathology Epithelium Free radicals Free Radicals - metabolism Hair Follicle - drug effects Hair Follicle - pathology Humans indole-3-acetic acid Indoleacetic Acids - administration & dosage Indoleacetic Acids - chemistry Indoleacetic Acids - pharmacology Indoleacetic Acids - therapeutic use Inflammation Lasers Light effects Male Mice Occlusion Photochemotherapy photodynamic therapy Photosensitization Photosensitizing Agents - administration & dosage Photosensitizing Agents - chemistry Photosensitizing Agents - pharmacology Photosensitizing Agents - therapeutic use Pilot Projects Propionibacterium acnes Propionibacterium acnes - drug effects Sebaceous Glands - drug effects Sebaceous Glands - pathology Sebaceous Glands - secretion Sebum - secretion Secretion Side effects Skin Staphylococcus aureus Staphylococcus aureus - drug effects Treatment Outcome U.V. radiation |
| title | Indole-3-acetic acid: A potential new photosensitizer for photodynamic therapy of acne vulgaris |
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