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Treatment of viral infections with 5-aminolevulinic acid and light

Background and Objective When 5‐aminolevulinic acid (ALA) is exogenously supplied, protoporphyrin IX (PpIX) is accumulated in various cells and makes them light sensitive. The possibility of using such an approach for the treatment of viral infections was studied in this work. Study Design/Materials...

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Published in:Lasers in surgery and medicine 1997, Vol.21 (4), p.351-358
Main Authors: Smetana, Zehava, Malik, Zvi, Orenstein, Arie, Mendelson, Ella, Ben-Hur, Ehud
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container_title Lasers in surgery and medicine
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creator Smetana, Zehava
Malik, Zvi
Orenstein, Arie
Mendelson, Ella
Ben-Hur, Ehud
description Background and Objective When 5‐aminolevulinic acid (ALA) is exogenously supplied, protoporphyrin IX (PpIX) is accumulated in various cells and makes them light sensitive. The possibility of using such an approach for the treatment of viral infections was studied in this work. Study Design/Materials and Methods ALA was added to cultured cells infected with human immunodeficiency virus (HIV). Accumulation of PpIX in the cells as well as virus infectivity after photodynamic treatment (PDT) were assessed. For in vivo studies, guinea pigs were infected with herpes simplex virus (HSV) and then administered ALA at intervals after infection. The animals were exposed to PDT at the site of infection 3 hours after ALA administration. Clinical observations and virus titration were made daily. For clinical studies, two patients with Molluscum contagiosum and Verrucae vulgares were treated with ALA fortified with an iron chelating agent and dimethylsulfoxide, followed 4 hours later by PDT. Results Cells that are infected with HIV accumulated PpIX upon addition of ALA in vitro. This accumulation was enhanced‐two‐fold in the presence of an iron chelator. Subsequent exposure to red light PDT drastically reduced the virus titer (> 99% for U1 cells latently infected with HIV). In guinea pigs infected with HSV, subsequent administration of ALA and exposure of the lesions to red light shortened the duration of vesicles' appearance from more than a week to a few days and reduced HSV titer in the lesions by ≥ 5 log10. ALA‐PDT treated AIDS patient suffering from Molluscum cotagiosum or a kidney transplant patient with Verrucae vulgares showed greatly improved clinical symptoms one month after treatment. Conclusion It is concluded that ALA‐PDT could be effective in treating certain viral infections, particularly those resulting in warts. Lasers Surg. Med. 21:351–358, 1997. © 1997 Wiley‐Liss, Inc.
doi_str_mv 10.1002/(SICI)1096-9101(1997)21:4<351::AID-LSM6>3.0.CO;2-P
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The possibility of using such an approach for the treatment of viral infections was studied in this work. Study Design/Materials and Methods ALA was added to cultured cells infected with human immunodeficiency virus (HIV). Accumulation of PpIX in the cells as well as virus infectivity after photodynamic treatment (PDT) were assessed. For in vivo studies, guinea pigs were infected with herpes simplex virus (HSV) and then administered ALA at intervals after infection. The animals were exposed to PDT at the site of infection 3 hours after ALA administration. Clinical observations and virus titration were made daily. For clinical studies, two patients with Molluscum contagiosum and Verrucae vulgares were treated with ALA fortified with an iron chelating agent and dimethylsulfoxide, followed 4 hours later by PDT. Results Cells that are infected with HIV accumulated PpIX upon addition of ALA in vitro. This accumulation was enhanced‐two‐fold in the presence of an iron chelator. Subsequent exposure to red light PDT drastically reduced the virus titer (&gt; 99% for U1 cells latently infected with HIV). In guinea pigs infected with HSV, subsequent administration of ALA and exposure of the lesions to red light shortened the duration of vesicles' appearance from more than a week to a few days and reduced HSV titer in the lesions by ≥ 5 log10. ALA‐PDT treated AIDS patient suffering from Molluscum cotagiosum or a kidney transplant patient with Verrucae vulgares showed greatly improved clinical symptoms one month after treatment. Conclusion It is concluded that ALA‐PDT could be effective in treating certain viral infections, particularly those resulting in warts. Lasers Surg. Med. 21:351–358, 1997. © 1997 Wiley‐Liss, Inc.</description><identifier>ISSN: 0196-8092</identifier><identifier>EISSN: 1096-9101</identifier><identifier>DOI: 10.1002/(SICI)1096-9101(1997)21:4&lt;351::AID-LSM6&gt;3.0.CO;2-P</identifier><identifier>PMID: 9328982</identifier><identifier>CODEN: LSMEDI</identifier><language>eng</language><publisher>New York: John Wiley &amp; Sons, Inc</publisher><subject>Acquired Immunodeficiency Syndrome - drug therapy ; AIDS/HIV ; Aminolevulinic Acid - therapeutic use ; Animals ; Biological and medical sciences ; Cell Line ; Female ; Guinea Pigs ; Herpes Simplex - drug therapy ; herpes simplex virus ; HIV-1 - drug effects ; human immunodeficiency virus ; Humans ; Male ; Medical sciences ; Molluscum Contagiosum - drug therapy ; Photochemotherapy - methods ; photodynamic treatment ; Protoporphyrins - biosynthesis ; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects) ; Technology. Biomaterials. Equipments. Material. Instrumentation ; Virus Diseases - drug therapy ; virus inactivation ; warts ; Warts - drug therapy</subject><ispartof>Lasers in surgery and medicine, 1997, Vol.21 (4), p.351-358</ispartof><rights>Copyright © 1997 Wiley‐Liss, Inc.</rights><rights>1997 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c4976-f00bbb87f5c8b4a2721c89b8dfa93b8792baed34c9da665961e8f61fe3b454163</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,4024,27923,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=2835277$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9328982$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Smetana, Zehava</creatorcontrib><creatorcontrib>Malik, Zvi</creatorcontrib><creatorcontrib>Orenstein, Arie</creatorcontrib><creatorcontrib>Mendelson, Ella</creatorcontrib><creatorcontrib>Ben-Hur, Ehud</creatorcontrib><title>Treatment of viral infections with 5-aminolevulinic acid and light</title><title>Lasers in surgery and medicine</title><addtitle>Lasers Surg. Med</addtitle><description>Background and Objective When 5‐aminolevulinic acid (ALA) is exogenously supplied, protoporphyrin IX (PpIX) is accumulated in various cells and makes them light sensitive. The possibility of using such an approach for the treatment of viral infections was studied in this work. Study Design/Materials and Methods ALA was added to cultured cells infected with human immunodeficiency virus (HIV). Accumulation of PpIX in the cells as well as virus infectivity after photodynamic treatment (PDT) were assessed. For in vivo studies, guinea pigs were infected with herpes simplex virus (HSV) and then administered ALA at intervals after infection. The animals were exposed to PDT at the site of infection 3 hours after ALA administration. Clinical observations and virus titration were made daily. For clinical studies, two patients with Molluscum contagiosum and Verrucae vulgares were treated with ALA fortified with an iron chelating agent and dimethylsulfoxide, followed 4 hours later by PDT. Results Cells that are infected with HIV accumulated PpIX upon addition of ALA in vitro. This accumulation was enhanced‐two‐fold in the presence of an iron chelator. Subsequent exposure to red light PDT drastically reduced the virus titer (&gt; 99% for U1 cells latently infected with HIV). In guinea pigs infected with HSV, subsequent administration of ALA and exposure of the lesions to red light shortened the duration of vesicles' appearance from more than a week to a few days and reduced HSV titer in the lesions by ≥ 5 log10. ALA‐PDT treated AIDS patient suffering from Molluscum cotagiosum or a kidney transplant patient with Verrucae vulgares showed greatly improved clinical symptoms one month after treatment. Conclusion It is concluded that ALA‐PDT could be effective in treating certain viral infections, particularly those resulting in warts. Lasers Surg. Med. 21:351–358, 1997. © 1997 Wiley‐Liss, Inc.</description><subject>Acquired Immunodeficiency Syndrome - drug therapy</subject><subject>AIDS/HIV</subject><subject>Aminolevulinic Acid - therapeutic use</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cell Line</subject><subject>Female</subject><subject>Guinea Pigs</subject><subject>Herpes Simplex - drug therapy</subject><subject>herpes simplex virus</subject><subject>HIV-1 - drug effects</subject><subject>human immunodeficiency virus</subject><subject>Humans</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Molluscum Contagiosum - drug therapy</subject><subject>Photochemotherapy - methods</subject><subject>photodynamic treatment</subject><subject>Protoporphyrins - biosynthesis</subject><subject>Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects)</subject><subject>Technology. Biomaterials. Equipments. Material. 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Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects)</topic><topic>Technology. Biomaterials. Equipments. Material. Instrumentation</topic><topic>Virus Diseases - drug therapy</topic><topic>virus inactivation</topic><topic>warts</topic><topic>Warts - drug therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Smetana, Zehava</creatorcontrib><creatorcontrib>Malik, Zvi</creatorcontrib><creatorcontrib>Orenstein, Arie</creatorcontrib><creatorcontrib>Mendelson, Ella</creatorcontrib><creatorcontrib>Ben-Hur, Ehud</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</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>Smetana, Zehava</au><au>Malik, Zvi</au><au>Orenstein, Arie</au><au>Mendelson, Ella</au><au>Ben-Hur, Ehud</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Treatment of viral infections with 5-aminolevulinic acid and light</atitle><jtitle>Lasers in surgery and medicine</jtitle><addtitle>Lasers Surg. Med</addtitle><date>1997</date><risdate>1997</risdate><volume>21</volume><issue>4</issue><spage>351</spage><epage>358</epage><pages>351-358</pages><issn>0196-8092</issn><eissn>1096-9101</eissn><coden>LSMEDI</coden><abstract>Background and Objective When 5‐aminolevulinic acid (ALA) is exogenously supplied, protoporphyrin IX (PpIX) is accumulated in various cells and makes them light sensitive. The possibility of using such an approach for the treatment of viral infections was studied in this work. Study Design/Materials and Methods ALA was added to cultured cells infected with human immunodeficiency virus (HIV). Accumulation of PpIX in the cells as well as virus infectivity after photodynamic treatment (PDT) were assessed. For in vivo studies, guinea pigs were infected with herpes simplex virus (HSV) and then administered ALA at intervals after infection. The animals were exposed to PDT at the site of infection 3 hours after ALA administration. Clinical observations and virus titration were made daily. For clinical studies, two patients with Molluscum contagiosum and Verrucae vulgares were treated with ALA fortified with an iron chelating agent and dimethylsulfoxide, followed 4 hours later by PDT. Results Cells that are infected with HIV accumulated PpIX upon addition of ALA in vitro. This accumulation was enhanced‐two‐fold in the presence of an iron chelator. Subsequent exposure to red light PDT drastically reduced the virus titer (&gt; 99% for U1 cells latently infected with HIV). In guinea pigs infected with HSV, subsequent administration of ALA and exposure of the lesions to red light shortened the duration of vesicles' appearance from more than a week to a few days and reduced HSV titer in the lesions by ≥ 5 log10. ALA‐PDT treated AIDS patient suffering from Molluscum cotagiosum or a kidney transplant patient with Verrucae vulgares showed greatly improved clinical symptoms one month after treatment. Conclusion It is concluded that ALA‐PDT could be effective in treating certain viral infections, particularly those resulting in warts. Lasers Surg. Med. 21:351–358, 1997. © 1997 Wiley‐Liss, Inc.</abstract><cop>New York</cop><pub>John Wiley &amp; Sons, Inc</pub><pmid>9328982</pmid><doi>10.1002/(SICI)1096-9101(1997)21:4&lt;351::AID-LSM6&gt;3.0.CO;2-P</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
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ispartof Lasers in surgery and medicine, 1997, Vol.21 (4), p.351-358
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subjects Acquired Immunodeficiency Syndrome - drug therapy
AIDS/HIV
Aminolevulinic Acid - therapeutic use
Animals
Biological and medical sciences
Cell Line
Female
Guinea Pigs
Herpes Simplex - drug therapy
herpes simplex virus
HIV-1 - drug effects
human immunodeficiency virus
Humans
Male
Medical sciences
Molluscum Contagiosum - drug therapy
Photochemotherapy - methods
photodynamic treatment
Protoporphyrins - biosynthesis
Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects)
Technology. Biomaterials. Equipments. Material. Instrumentation
Virus Diseases - drug therapy
virus inactivation
warts
Warts - drug therapy
title Treatment of viral infections with 5-aminolevulinic acid and light
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