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Garcia-Mouronte E, Naharro-Rodriguez J, Alonso-Mtz de Salinas L, Pérez-González LA, Fernández-Guarino M. Self-Applied Daylight Photodynamic Therapy: A Paradigm Shift? Int J Mol Sci 2025; 26:628. [PMID: 39859342 PMCID: PMC11766313 DOI: 10.3390/ijms26020628] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Revised: 12/31/2024] [Accepted: 01/09/2025] [Indexed: 01/27/2025] Open
Abstract
Photodynamic therapy (PDT) involves the topical application of a photosensitizer and its activation by visible light, leading to the generation of protoporphyrin IX (PpIX) and reactive oxygen species. Daylight photodynamic therapy (dPDT), a variant utilizing natural sunlight as the energy source, enhances procedural flexibility by eliminating the need for specialized equipment. dPDT has been effectively used in dermatology to treat various cutaneous disorders, including neoplastic and infectious diseases. Traditionally, skin preparation and photosensitizer application are performed by trained practitioners, limiting the accessibility of dPDT for broader populations. However, recent studies suggest that these preparatory steps can be managed by patients or caregivers, enabling fully self-applied, home-based dPDT protocols. This review systematically examines the current evidence on self-applied dPDT (SA-dPDT), emphasizing molecular mechanisms and its efficacy in managing premalignant and other cutaneous conditions.
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Affiliation(s)
- Emilio Garcia-Mouronte
- Dermatology Department, Hospital Universitario Ramon y Cajal, Carretera M-607 km 9.1, 28034 Madrid, Spain; (J.N.-R.); (L.A.-M.d.S.); (L.A.P.-G.)
| | | | | | | | - Montserrat Fernández-Guarino
- Dermatology Department, Hospital Universitario Ramon y Cajal, Carretera M-607 km 9.1, 28034 Madrid, Spain; (J.N.-R.); (L.A.-M.d.S.); (L.A.P.-G.)
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Balakirski G, Lehmann P, Szeimies R, Hofmann SC. Photodynamic therapy in dermatology: established and new indications. J Dtsch Dermatol Ges 2024; 22:1651-1662. [PMID: 39226531 PMCID: PMC11626226 DOI: 10.1111/ddg.15464] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2023] [Accepted: 04/22/2024] [Indexed: 09/05/2024]
Abstract
Photodynamic therapy (PDT) is internationally established as an approved treatment option for in situ forms of keratinocytic skin cancer (actinic keratoses, Bowen's disease, basal cell carcinoma). For these indications, there are standardized treatment protocols using narrow-spectrum light sources or (artificial) daylight, the use of which is associated with successful healing, a low rate of lesion recurrence, and a very good cosmetic result. Daylight PDT is superior to conventional PDT in terms of significantly less pain and associated higher patient acceptance. Newer indications, for which no approval has yet been granted, but which nevertheless have sufficient evidence of efficacy according to the study situation, are inflammatory (lichen sclerosus, acne) and infectious dermatoses (viral warts, cutaneous leishmaniasis, atypical mycobacteriosis). In addition, PDT is increasingly being used in aesthetic dermatology with the aim of skin rejuvenation.
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Affiliation(s)
- Galina Balakirski
- Center for DermatologyAllergology and DermatosurgeryHelios University Hospital WuppertalUniversity of Witten/HerdeckeWuppertalGermany
| | - Percy Lehmann
- Center for DermatologyAllergology and DermatosurgeryHelios University Hospital WuppertalUniversity of Witten/HerdeckeWuppertalGermany
| | - Rolf‐Markus Szeimies
- Department of Dermatology and AllergologyKlinikum Vest GmbHRecklinghausenAcademic Teaching Hospital of Ruhr University BochumRecklinghausenGermany
| | - Silke C. Hofmann
- Center for DermatologyAllergology and DermatosurgeryHelios University Hospital WuppertalUniversity of Witten/HerdeckeWuppertalGermany
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3
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Ullah N, Sagar M, Abidin ZU, Naeem MA, Din SZU, Ahmad I. Photodynamic therapy in management of cutaneous leishmaniasis: A systematic review. Lasers Med Sci 2024; 39:226. [PMID: 39207568 DOI: 10.1007/s10103-024-04174-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2024] [Accepted: 08/15/2024] [Indexed: 09/04/2024]
Abstract
This systematic review evaluated the efficacy and safety of photodynamic therapy (PDT) in the management of cutaneous leishmaniasis (CL). The electronic search for identification of relevant studies, adhered to the PICOS (Population, Intervention, Comparator, Outcomes and Study type) framework, was conducted through PubMed, Google scholar, Dimensions, X-mol, and Semantic Scholar till December 2023. All types of studies reporting PDT in the management of CL with no language restriction were included. Methodological quality appraised of the selected studies was performed using Jadad index. Of the 317 identified studies, 21 reported PDT for the treatment of CL lesions, consisting of two randomized controlled trials (RCTs), four single-center open study, one case series and 14 case reports. Collectively, these studies presented a total of 304 patients with ages ranging from 1 to 82 years, undergoing varying number of PDT sessions (3-28) and follow-up durations spanning 4 weeks to 24 months. The CL lesions predominantly manifested on the exposed body areas, such as face, limbs, neck, ear and nose, and characterized with the use of clinical variables, such as plaques, papules, erythema and ulceration. PDT protocols differed in the photosensitizer type, incubation time, light source characteristics (e.g., wavelength, output power, and energy density), duration of light illumination, number of PDT sessions and their respective frequencies. Treatment response was assessed through the clinical presentation (i.e., at the baseline and after PDT completion) or by the absence of Leishmania parasites. Adverse effects comprised of pain, burning and tingling sensation experienced during PDT, followed by erythema, pigmentation changes and edema post-treatment. This systematic review revealed that PDT is an efficacious and safe modality for the treatment of CL, with mild and transient side effects.
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Affiliation(s)
- Naeem Ullah
- Department of Physics, Islamia College Peshawar, Khyber Pakhtunkhwa, Pakistan
| | | | - Zain Ul Abidin
- Institute of Engineering and Applied Sciences (PIEAS), Nilore, Islamabad, Pakistan
| | | | - Syed Zaheer Ud Din
- International School for Optoelectronic Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250353, China
| | - Iftikhar Ahmad
- Institute of Radiotherapy and Nuclear Medicine (IRNUM), Peshawar, Pakistan.
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Çalişkan E, Uncu HB, Akoğlu G. Cutaneous leishmaniasis treated with daylight methylene blue photodynamic therapy. Int J Dermatol 2024; 63:e65-e67. [PMID: 38093460 DOI: 10.1111/ijd.16977] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Revised: 11/26/2023] [Accepted: 11/30/2023] [Indexed: 01/19/2024]
Affiliation(s)
- Ercan Çalişkan
- Department of Dermatology and Venereology, University of Health Sciences, Gulhane Training and Research Hospital, Ankara, Turkey
| | - Hüma B Uncu
- Department of Dermatology and Venereology, University of Health Sciences, Gulhane Training and Research Hospital, Ankara, Turkey
| | - Gülşen Akoğlu
- Department of Dermatology and Venereology, University of Health Sciences, Gulhane Training and Research Hospital, Ankara, Turkey
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Din SZU, Ahmed K, Rengasamy KR, Gul N, Ahmad I. Re: Efficacy of photodynamic therapy in cutaneous leishmaniasis: A systematic review. Photodiagnosis Photodyn Ther 2024; 45:103957. [PMID: 38161038 DOI: 10.1016/j.pdpdt.2023.103957] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2023] [Revised: 12/07/2023] [Accepted: 12/28/2023] [Indexed: 01/03/2024]
Affiliation(s)
- Syed Zaheer Ud Din
- International School for Optoelectronic Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, China
| | - Kamran Ahmed
- Rawalpindi Medical University, Rawalpindi, Pakistan
| | - Kannan Rr Rengasamy
- Laboratory of Natural Products and Medicinal Chemistry (LNPMC), Center for Global Health Research, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences (SIMATS), Thandalam, Chennai 602107, India
| | - Neelam Gul
- Institute of Radiotherapy and Nuclear Medicine (IRNUM), Peshawar, Pakistan
| | - Iftikhar Ahmad
- Institute of Radiotherapy and Nuclear Medicine (IRNUM), Peshawar, Pakistan.
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Luo OD, Bose R, Bawazir MA, Thuraisingam T, Ghazawi FM. A Review of the Dermatologic Clinical Applications of Topical Photodynamic Therapy. J Cutan Med Surg 2024; 28:NP1. [PMID: 38243786 DOI: 10.1177/12034754231216969] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2024]
Abstract
Topical photodynamic therapy is a widely approved therapy for actinic keratoses and low-risk nonmelanoma skin cancers with a rapidly growing range of emerging indications for other cutaneous diseases. This review summarizes the best-available evidence to provide a clinical update for dermatologists on the approved and emerging indications of photodynamic therapy. The body of evidence suggests that photodynamic therapy is superior or noninferior to other available treatment modalities for actinic keratoses, low-risk basal cell carcinomas, Bowen's disease, skin field cancerization, chemoprevention of keratinocyte carcinomas in organ transplant recipients, photoaging, acne vulgaris, and cutaneous infections including verrucae, onychomycosis, and cutaneous leishmaniasis. There is emerging evidence that photodynamic therapy plays a role in the management of actinic cheilitis, early-stage mycosis fungoides, extramammary Paget disease, lichen sclerosis, and folliculitis decalvans but there are no comparative studies with other active treatment modalities. Common barriers to topical photodynamic therapy include procedural pain, costs, and the time required for treatment delivery. There is significant heterogeneity in the photodynamic therapy protocols reported in the literature, including different photosensitizers, light sources, number of treatments, time between treatments, and use of procedural analgesia. Topical photodynamic therapy should be considered in the management of a spectrum of inflammatory, neoplastic, and infectious dermatoses. However, more comparative research is required to determine its role in the treatment algorithm for these dermatologic conditions and more methodological research is required to optimize photodynamic therapy protocols to improve the tolerability of the procedure for patients.
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Affiliation(s)
- Owen Dan Luo
- Department of Medicine, McGill University, Montreal, QC, Canada
| | - Reetesh Bose
- Division of Dermatology, Department of Medicine, University of Ottawa, Ottawa, ON, Canada
| | - Mohammed A Bawazir
- Division of Dermatology, Department of Medicine, McMaster University, Hamilton, ON, Canada
| | - Thusanth Thuraisingam
- Division of Dermatology, Department of Medicine, University of Ottawa, Ottawa, ON, Canada
- Division of Dermatology, Department of Medicine, McGill University, Montreal, QC, Canada
| | - Feras M Ghazawi
- Division of Dermatology, Department of Medicine, University of Ottawa, Ottawa, ON, Canada
- Division of Dermatology, Department of Medicine, McGill University, Montreal, QC, Canada
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Li Pomi F, Peterle L, Vaccaro M, Borgia F. Daylight photodynamic therapy for cutaneous leishmaniasis in a pediatric setting: A case report and literature review. Photodiagnosis Photodyn Ther 2023; 44:103800. [PMID: 37734562 DOI: 10.1016/j.pdpdt.2023.103800] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Revised: 09/08/2023] [Accepted: 09/08/2023] [Indexed: 09/23/2023]
Abstract
Cutaneous leishmaniasis (CL) is a vector-borne infection caused by the obligate intracellular parasites of the Leishmania genus. Children are more frequently affected due to increased exposure to sandflies and underdeveloped immune system. Currently, there is a lack of consensus on the most effective treatment approach for CL since most drugs are accompanied by numerous limitations, including adverse effects, toxicity, and onset of antimicrobial resistance phenomena. These limitations appear more relevant in the pediatric population, both for the treatment-related risks and for the reticence of the parents. Photodynamic therapy (PDT) has been increasingly employed in numerous inflammatory and infectious diseases, owing to its tissue selectivity and excellent cosmetic outcomes. On this topic, we report our experience with daylight-PDT (DL-PDT) therapy in a difficult-to-treat area like the facial region in a child with a six-month history of CL. Our case is paradigmatic of the potentiality of PDT to treat difficult lesions in a pediatric setting. However, its use has not yet been standardized either for the treatment of leishmania, with high variability in the number of sessions and time intervals. Specific protocols for pediatric patients should be better standardized in randomized clinical trials in order to provide clear indications for clinicians.
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Affiliation(s)
- Federica Li Pomi
- Department of Clinical and Experimental Medicine, Section of Dermatology, University of Messina, Messina 98125, Italy
| | - Lucia Peterle
- Department of Clinical and Experimental Medicine, Section of Dermatology, University of Messina, Messina 98125, Italy
| | - Mario Vaccaro
- Department of Clinical and Experimental Medicine, Section of Dermatology, University of Messina, Messina 98125, Italy
| | - Francesco Borgia
- Department of Clinical and Experimental Medicine, Section of Dermatology, University of Messina, Messina 98125, Italy.
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8
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Liu L, He Y, Chang J. Efficacy of photodynamic therapy in cutaneous leishmaniasis: A systematic review. Photodiagnosis Photodyn Ther 2023; 43:103627. [PMID: 37245683 DOI: 10.1016/j.pdpdt.2023.103627] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Revised: 05/08/2023] [Accepted: 05/19/2023] [Indexed: 05/30/2023]
Abstract
OBJECTIVE To systematically review the efficacy of photodynamic therapy (PDT) in the treatment of cutaneous leishmaniasis (CL). METHODS PubMed, Embase and Cochrane Library databases were searched for articles published by November 16, 2022, with no time restrictions. 'Cutaneous leishmaniasis' and 'photodynamic therapy' were searched using predefined search strings. INCLUSION CRITERIA (i) Randomized control trials; (ii) controlled clinical trials; (iii) case series; (iv) case reports; (v) participants were humans; (vi) clinical diagnosis was CL; (vii) treatment method used was PDT; and (viii) articles published in English. RESULTS In total, 303 articles were identified, including 14 papers meeting the criteria. The number of patients in each study ranged from 1 to 60 and the age ranged from 1 to 82 years. Aminolevulinic acid and methyl aminolevulinate were used as photosensitizers. Red light and sunlight were used as light sources. All reported satisfactory clinical effects. Side effects of treatment included burning sensation, pain and pigmentation after treatment. However, they were tolerable and temporary. The follow-up time ranged between 9 weeks and 24 months. A total of two patients recurred, but one did not recur after another round of PDT during the follow-up period. CONCLUSIONS The present study suggests that PDT is a safe and effective method for the treatment of CL, with tolerable side effects and good efficacy. As an alternative treatment method of CL, PDT has great potential. However, to verify the efficacy and specific mechanism of PDT for the optimal treatment strategy of CL, further research with larger sample sizes and longer follow-up times are needed.
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Affiliation(s)
- Lin Liu
- Department of Dermatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China; Peking Union Medical College, Chinese Academy of Medical Sciences, Graduate School of Peking Union Medical College, Beijing, China
| | - Yuexi He
- Department of Dermatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China; Peking Union Medical College, Chinese Academy of Medical Sciences, Graduate School of Peking Union Medical College, Beijing, China
| | - Jianmin Chang
- Department of Dermatology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China; Peking Union Medical College, Chinese Academy of Medical Sciences, Graduate School of Peking Union Medical College, Beijing, China.
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9
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Piksa M, Lian C, Samuel IC, Pawlik KJ, Samuel IDW, Matczyszyn K. The role of the light source in antimicrobial photodynamic therapy. Chem Soc Rev 2023; 52:1697-1722. [PMID: 36779328 DOI: 10.1039/d0cs01051k] [Citation(s) in RCA: 97] [Impact Index Per Article: 48.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/14/2023]
Abstract
Antimicrobial photodynamic therapy (APDT) is a promising approach to fight the growing problem of antimicrobial resistance that threatens health care, food security and agriculture. APDT uses light to excite a light-activated chemical (photosensitiser), leading to the generation of reactive oxygen species (ROS). Many APDT studies confirm its efficacy in vitro and in vivo against bacteria, fungi, viruses and parasites. However, the development of the field is focused on exploring potential targets and developing new photosensitisers. The role of light, a crucial element for ROS production, has been neglected. What are the main parameters essential for effective photosensitiser activation? Does an optimal light radiant exposure exist? And finally, which light source is best? Many reports have described the promising antibacterial effects of APDT in vitro, however, its application in vivo, especially in clinical settings remains very limited. The restricted availability may partially be due to a lack of standard conditions or protocols, arising from the diversity of selected photosensitising agents (PS), variable testing conditions including light sources used for PS activation and methods of measuring anti-bacterial activity and their effectiveness in treating bacterial infections. We thus sought to systematically review and examine the evidence from existing studies on APDT associated with the light source used. We show how the reduction of pathogens depends on the light source applied, radiant exposure and irradiance of light used, and type of pathogen, and so critically appraise the current state of development of APDT and areas to be addressed in future studies. We anticipate that further standardisation of the experimental conditions will help the field advance, and suggest key optical and biological parameters that should be reported in all APDT studies. More in vivo and clinical studies are needed and are expected to be facilitated by advances in light sources, leading to APDT becoming a sustainable, alternative therapeutic option for bacterial and other microbial infections in the future.
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Affiliation(s)
- Marta Piksa
- Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Science, Weigla 12, 53-114, Wroclaw, Poland
| | - Cheng Lian
- Organic Semiconductor Centre, SUPA, School of Physics and Astronomy, University of St Andrews, Fife, KY16 9SS, UK.
| | - Imogen C Samuel
- School of Medicine, University of Manchester, Manchester, M13 9PL, UK
| | - Krzysztof J Pawlik
- Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Science, Weigla 12, 53-114, Wroclaw, Poland
| | - Ifor D W Samuel
- Organic Semiconductor Centre, SUPA, School of Physics and Astronomy, University of St Andrews, Fife, KY16 9SS, UK.
| | - Katarzyna Matczyszyn
- Institute of Advanced Materials, Faculty of Chemistry, Wroclaw University of Science and Technology, Wyb. Wyspianskiego 27, 50-370 Wroclaw, Poland.
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10
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Burmann SN, Oellig F, Paschos A, Hofmann SC, Lehmann P, Kreuter A, Balakirski G. [Successful treatment of Old World cutaneous leishmaniasis with red or green light photodynamic therapy]. DERMATOLOGIE (HEIDELBERG, GERMANY) 2022; 73:952-958. [PMID: 35951076 DOI: 10.1007/s00105-022-05038-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 07/14/2022] [Indexed: 06/15/2023]
Abstract
Cutaneous leishmaniasis is one of the most common travel dermatoses in Germany, which can be acquired not only in Africa, Asia or the American continent, but also in southern European countries. In addition to the currently available topical and systemic therapy options, there have been increasing reports of successful treatment of cutaneous leishmaniasis with photodynamic therapy (PDT) using numerous therapy regimens and different photosensitizers in recent years. We report on successful photodynamic therapy of Old World cutaneous leishmaniasis with red and green light PDT with 10% 5‑aminolevulinic acid.
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Affiliation(s)
- Sven-Niklas Burmann
- Klinik für Dermatologie, Venerologie und Allergologie, Helios St. Elisabeth Klinik Oberhausen, Universität Witten/Herdecke, Josefstr. 3, 46045, Oberhausen, Deutschland
| | - Frank Oellig
- Pathologie Rhein-Ruhr, Mülheim an der Ruhr, Deutschland
| | - Alexandros Paschos
- Klinik für Dermatologie, Venerologie und Allergologie, Helios St. Elisabeth Klinik Oberhausen, Universität Witten/Herdecke, Josefstr. 3, 46045, Oberhausen, Deutschland
| | - Silke C Hofmann
- Zentrum für Dermatologie, Allergologie und Dermatochirurgie, Helios Universitätsklinikum Wuppertal, Universität Witten/Herdecke, Heusnerstr. 40, 42283, Wuppertal, Deutschland
| | - Percy Lehmann
- Zentrum für Dermatologie, Allergologie und Dermatochirurgie, Helios Universitätsklinikum Wuppertal, Universität Witten/Herdecke, Heusnerstr. 40, 42283, Wuppertal, Deutschland
| | - Alexander Kreuter
- Klinik für Dermatologie, Venerologie und Allergologie, Helios St. Elisabeth Klinik Oberhausen, Universität Witten/Herdecke, Josefstr. 3, 46045, Oberhausen, Deutschland.
- Klinik für Dermatologie, Venerologie und Allergologie, Helios St. Johannes Klinik Duisburg, Dieselstr. 185, 47166, Duisburg, Deutschland.
| | - Galina Balakirski
- Zentrum für Dermatologie, Allergologie und Dermatochirurgie, Helios Universitätsklinikum Wuppertal, Universität Witten/Herdecke, Heusnerstr. 40, 42283, Wuppertal, Deutschland
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11
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Barba PJ, Morgado-Carrasco D, Quera A. [Translated article] Miltefosine to Treat Childhood Cutaneous Leishmaniasis. ACTAS DERMO-SIFILIOGRAFICAS 2022; 113:T827-T831. [PMID: 35817154 DOI: 10.1016/j.ad.2022.07.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Accepted: 11/22/2020] [Indexed: 11/29/2022] Open
Affiliation(s)
- P J Barba
- Servicio de Dermatología, H.I.G.A Prof. Dr. Rodolfo Rossi, La Plata, Argentina.
| | - D Morgado-Carrasco
- Servicio de Dermatología, Hospital Clínic de Barcelona, Barcelona, Spain
| | - A Quera
- Servicio de Patología, Hospital de Figueres, Fundació Salut Empordà, Spain
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12
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Barba P, Morgado-Carrasco D, Quera A. Tratamiento de leishmaniasis cutánea infantil con miltefosina. ACTAS DERMO-SIFILIOGRAFICAS 2022; 113:827-831. [DOI: 10.1016/j.ad.2020.11.033] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 10/15/2020] [Accepted: 11/22/2020] [Indexed: 11/27/2022] Open
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Ning X, He G, Zeng W, Xia Y. The photosensitizer-based therapies enhance the repairing of skin wounds. Front Med (Lausanne) 2022; 9:915548. [PMID: 36035433 PMCID: PMC9403269 DOI: 10.3389/fmed.2022.915548] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 07/26/2022] [Indexed: 11/29/2022] Open
Abstract
Wound repair remains a clinical challenge and bacterial infection is a common complication that may significantly delay healing. Therefore, proper and effective wound management is essential. The photosensitizer-based therapies mainly stimulate the photosensitizer to generate reactive oxygen species through appropriate excitation source irradiation, thereby killing pathogenic microorganisms. Moreover, they initiate local immune responses by inducing the recruitment of immune cells as well as the production of proinflammatory cytokines. In addition, these therapies can stimulate the proliferation, migration and differentiation of skin resident cells, and improve the deposition of extracellular matrix; subsequently, they promote the re-epithelialization, angiogenesis, and tissue remodeling. Studies in multiple animal models and human skin wounds have proved that the superior sterilization property and biological effects of photosensitizer-based therapies during different stages of wound repair. In this review, we summarize the recent advances in photosensitizer-based therapies for enhancing tissue regeneration, and suggest more effective therapeutics for patients with skin wounds.
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Affiliation(s)
- Xiaoying Ning
- Department of Dermatology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Gang He
- State Key Laboratory for Strength and Vibration of Mechanical Structures, Frontier Institute of Science and Technology, Xi’an Jiaotong University, Xi’an, China
- Xi’an Key Laboratory of Sustainable Energy Materials Chemistry, Frontier Institute of Science and Technology, Xi’an Jiaotong University, Xi’an, China
| | - Weihui Zeng
- Department of Dermatology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Yumin Xia
- Department of Dermatology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- *Correspondence: Yumin Xia,
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14
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Alamon-Reig F, Martí-Martí I, Loughlin CRM, Garcia A, Carrera C, Aguilera-Peiró P. Successful treatment of facial cutaneous leishmaniasis with photodynamic therapy. Indian J Dermatol Venereol Leprol 2022; 88:667-670. [DOI: 10.25259/ijdvl_1175_2021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Accepted: 02/01/2022] [Indexed: 11/04/2022]
Affiliation(s)
| | | | | | - Adriana Garcia
- Department of Pathology, Hospital Clínic de Barcelona, University of Barcelona, Barcelona, Spain
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15
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Ozlem-Caliskan S, Ertabaklar H, Bilgin MD, Ertug S. Evaluation of photodynamic therapy against Leishmania tropica promastigotes using different photosensitizers. PHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE 2022; 38:354-364. [PMID: 34897808 DOI: 10.1111/phpp.12758] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Revised: 11/24/2021] [Accepted: 12/09/2021] [Indexed: 06/14/2023]
Abstract
BACKGROUND Photodynamic therapy is a two-step procedure, involving the use of photosensitizing agents followed by selective illumination of the target lesion with visible light. Photodynamic therapy has been described recently as a promising strategy for treatment of leishmaniasis. This study aims to evaluate the in vitro phototoxic, morphological, and apoptotic effect of methylene blue, toluidine blue, chloro-aluminum phthalocyanine, and pheophorbide a-mediated photodynamic therapy on the viability of Leishmania tropica promastigotes. METHODS Parasites were treated with methylene blue, toluidine blue, chloro-aluminum phthalocyanine, and pheophorbide a or/and methylene blue, toluidine blue, chloro-aluminum phthalocyanine, and pheophorbide a-mediated photodynamic therapy, and cell proliferation, morphological changes, and apoptosis were evaluated by XTT, giemsa staining, DAPI staining, and DNA fragmentation, respectively. RESULTS Parasite viability was significantly different in between the groups treated with methylene blue, toluidine blue, and pheophorbide a, with or without irradiation. chloro-aluminum phthalocyanine treatment did not lead to any alterations in cell viability in Leishmania tropica promastigotes with or without irradiation. DAPI staining results indicated that apoptotic bodies and nucleus fragmentation started to be visible in methylene blue, chloro-aluminum phthalocyanine, and pheophorbide a-mediated photodynamic therapy groups. DNA ladder pattern which is used to define apoptosis was observed in irradiated methylene blue, chloro-aluminum phthalocyanine, and pheophorbide a groups. CONCLUSIONS The results revealed that apoptosis-induced cell death was observed in Leishmania tropica promastigotes after the application of photosensitizers in combination with light irradiation.
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Affiliation(s)
- Sercin Ozlem-Caliskan
- Department of Biophysics, Institute of Health Sciences, Aydin Adnan Menderes University, Aydin, Turkey
| | - Hatice Ertabaklar
- Department of Parasitology, Faculty of Medicine, Aydin Adnan Menderes University, Aydin, Turkey
| | - Mehmet Dincer Bilgin
- Department of Biophysics, Faculty of Medicine, Aydin Adnan Menderes University, Aydin, Turkey
| | - Sema Ertug
- Department of Parasitology, Faculty of Medicine, Aydin Adnan Menderes University, Aydin, Turkey
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16
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Effects of Blue Light on the Skin and Its Therapeutic Uses: Photodynamic Therapy and Beyond. Dermatol Surg 2022; 48:802-808. [DOI: 10.1097/dss.0000000000003500] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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17
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The evolution of clinical guidelines for antimicrobial photodynamic therapy of skin. Photochem Photobiol Sci 2022; 21:385-395. [PMID: 35132604 PMCID: PMC8821777 DOI: 10.1007/s43630-021-00169-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Accepted: 12/28/2021] [Indexed: 11/28/2022]
Abstract
Antimicrobial photodynamic therapy has become an important component in the treatment of human infection. This review considers historical guidelines, and the scientific literature to envisage what future clinical guidelines for treating skin infection might include. Antibiotic resistance, vertical and horizontal infection control strategies and a range of technologies effective in eradicating microbes without building up new resistance are described. The mechanism of action of these treatments and examples of their clinical use are also included. The research recommendations of NICE Guidelines on the dermatological manifestations of microbial infection were also reviewed to identify potential applications for PDT. The resistance of some microbes to antibiotics can be halted, or even reversed through the use of supplementary drugs, and so they are likely to persist as a treatment of infection. Conventional PDT will undoubtedly continue to be used for a range of skin conditions given existing healthcare infrastructure and a large evidence base. Daylight PDT may find broader antimicrobial applications than just Acne and Cutaneous Leishmaniasis, and Ambulatory PDT devices could become popular in regions where resources are limited or daylight exposure is not possible or inappropriate. Nanotheranostics were found to be highly relevant, and often include PDT, however, new treatments and novel applications and combinations of existing treatments will be subject to Clinical Trials.
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18
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Varzandeh M, Mohammadinejad R, Esmaeilzadeh-Salestani K, Dehshahri A, Zarrabi A, Aghaei-Afshar A. Photodynamic therapy for leishmaniasis: Recent advances and future trends. Photodiagnosis Photodyn Ther 2021; 36:102609. [PMID: 34728420 DOI: 10.1016/j.pdpdt.2021.102609] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 10/15/2021] [Accepted: 10/27/2021] [Indexed: 02/06/2023]
Abstract
Leishmaniasis has infected more than 12 million people worldwide. This neglected tropical disease, causing 20,000-30,000 deaths per year, is a global health problem. The emergence of resistant parasites and serious side effects of conventional therapies has led to the search for less toxic and non-invasive alternative treatments. Photodynamic therapy is a promising therapeutic strategy to produce reactive oxygen species for the treatment of leishmaniasis. In this regard, natural and synthetic photosensitizers such as curcumin, hypericin, 5-aminolevulinic acid, phthalocyanines, phenothiazines, porphyrins, chlorins and nanoparticles have been applied. In this review, the recent advances on using photodynamic therapy for treating Leishmania species have been reviewed.
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Affiliation(s)
- Mohammad Varzandeh
- Department of Materials Engineering, Isfahan University of Technology, Isfahan 84156-83111, Iran
| | - Reza Mohammadinejad
- Research Center of Tropical and Infectious Diseases, Kerman University of Medical Sciences, Kerman, Iran
| | - Keyvan Esmaeilzadeh-Salestani
- Chair of Crop Science and Plant Biology, Institute of Agricultural and Environmental Sciences, Estonian University of Life Sciences, Fr. R.Kreutzwaldi 1, EE51014 Tartu, Estonia
| | - Ali Dehshahri
- Pharmaceutical Sciences Research Center, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ali Zarrabi
- Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Istinye University, 34485 Istanbul, Turkey
| | - Abbas Aghaei-Afshar
- Research Center of Tropical and Infectious Diseases, Kerman University of Medical Sciences, Kerman, Iran.
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19
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Hobelsberger S, Krauß MP, Bogdan C, Aschoff R. [Successful treatment of cutaneous leishmaniasis with simulated daylight photodynamic therapy]. Hautarzt 2021; 73:376-378. [PMID: 34213573 DOI: 10.1007/s00105-021-04852-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/31/2021] [Indexed: 11/28/2022]
Abstract
A 5-year-old Syrian boy , presented with a complex cutaneous leishmaniasis (CL) of the right ankle caused by Leishmania (L.) tropica. The patient received photodynamic therapy (PDT; 6 cycles with application of 5‑aminolevulinic acid and foil occlusion for 3 h). Due to pain during exposure to red light, exposure was continued with simulated daylight (sDL-PDT). The lesion healed with an atrophic scar. Due to fewer side effects and less pain, sDL-PDT seems to be a good therapeutic strategy for CL caused by L. tropica.
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Affiliation(s)
- Sarah Hobelsberger
- Klinik und Poliklinik für Dermatologie, Universitätsklinikum Carl Gustav Carus Dresden, Fetscherstr. 74, 01307, Dresden, Deutschland.
| | - Marie-Paloma Krauß
- Klinik und Poliklinik für Dermatologie, Universitätsklinikum Carl Gustav Carus Dresden, Fetscherstr. 74, 01307, Dresden, Deutschland
| | - Christian Bogdan
- Mikrobiologisches Institut - Klinische Mikrobiologie, Immunologie und Hygiene Universitätsklinikum Erlangen und Friedrich-Alexander-Universität (FAU) Erlangen-Nürnberg, Erlangen-Nürnberg, Deutschland
| | - Roland Aschoff
- Klinik und Poliklinik für Dermatologie, Universitätsklinikum Carl Gustav Carus Dresden, Fetscherstr. 74, 01307, Dresden, Deutschland
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20
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De Silva P, Saad MA, Thomsen HC, Bano S, Ashraf S, Hasan T. Photodynamic therapy, priming and optical imaging: Potential co-conspirators in treatment design and optimization - a Thomas Dougherty Award for Excellence in PDT paper. J PORPHYR PHTHALOCYA 2020; 24:1320-1360. [PMID: 37425217 PMCID: PMC10327884 DOI: 10.1142/s1088424620300098] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/25/2023]
Abstract
Photodynamic therapy is a photochemistry-based approach, approved for the treatment of several malignant and non-malignant pathologies. It relies on the use of a non-toxic, light activatable chemical, photosensitizer, which preferentially accumulates in tissues/cells and, upon irradiation with the appropriate wavelength of light, confers cytotoxicity by generation of reactive molecular species. The preferential accumulation however is not universal and, depending on the anatomical site, the ratio of tumor to normal tissue may be reversed in favor of normal tissue. Under such circumstances, control of the volume of light illumination provides a second handle of selectivity. Singlet oxygen is the putative favorite reactive molecular species although other entities such as nitric oxide have been credibly implicated. Typically, most photosensitizers in current clinical use have a finite quantum yield of fluorescence which is exploited for surgery guidance and can also be incorporated for monitoring and treatment design. In addition, the photodynamic process alters the cellular, stromal, and/or vascular microenvironment transiently in a process termed photodynamic priming, making it more receptive to subsequent additional therapies including chemo- and immunotherapy. Thus, photodynamic priming may be considered as an enabling technology for the more commonly used frontline treatments. Recently, there has been an increase in the exploitation of the theranostic potential of photodynamic therapy in different preclinical and clinical settings with the use of new photosensitizer formulations and combinatorial therapeutic options. The emergence of nanomedicine has further added to the repertoire of photodynamic therapy's potential and the convergence and co-evolution of these two exciting tools is expected to push the barriers of smart therapies, where such optical approaches might have a special niche. This review provides a perspective on current status of photodynamic therapy in anti-cancer and anti-microbial therapies and it suggests how evolving technologies combined with photochemically-initiated molecular processes may be exploited to become co-conspirators in optimization of treatment outcomes. We also project, at least for the short term, the direction that this modality may be taking in the near future.
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Affiliation(s)
- Pushpamali De Silva
- Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
| | - Mohammad A. Saad
- Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
| | - Hanna C. Thomsen
- Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
| | - Shazia Bano
- Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
| | - Shoaib Ashraf
- Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
| | - Tayyaba Hasan
- Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA
- Division of Health Sciences and Technology, Harvard University and Massachusetts Institute of Technology, Cambridge, MA 02139, USA
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21
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Kremer N, Sherman S, Lapidoth M, Enk CD, Leshem YA, Mimouni T, Dudkiewicz D, Hodak E, Levi A. Self-administered daylight-activated photodynamic therapy for the treatment of hand eczema: A prospective proof-of-concept study. Dermatol Ther 2020; 33:e14329. [PMID: 32975350 DOI: 10.1111/dth.14329] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2020] [Revised: 09/06/2020] [Accepted: 09/10/2020] [Indexed: 12/16/2022]
Abstract
Photodynamic therapy (PDT), traditionally used in patients with nonmelanoma skin cancer, has been found to be effective for various inflammatory skin conditions. Daylight-activated PDT (DL-PDT), in which the sun serves as the light source, is substantially less painful than conventional PDT. This study aimed to determine the safety and efficacy of DL-PDT in a series of patients with chronic hand eczema (CHE). A proof-of-concept prospective design was used. Eight patients diagnosed with CHE at a tertiary dermatology clinic underwent DL-PDT. The first treatment was administered at the clinic and subsequent treatments (up to four total) were self-administered at home at 2-week intervals. Outcome was evaluated with the Investigator Global Assessment (IGA; score 0-4), Dermatology Life Quality Index (DLQI; score 0-24), and blinded review of clinical photographs (graded on a quartile scale by percent improvement). There were six male and two female patients of mean age 35 years. All underwent at least three treatments. The IGA score improved by 2.5 points at 1 month, 2.7 at 3 months, and 2.2 at 6 months post-treatment, and the DLQI score improved by 7.9, 6.6, and 6.1 points, respectively. Clinical photograph grades improved by 2.9 points at 3 months. Side effects were mild and transient. All patients had some degree of recurrence after 6 months of treatment. The self-administered DL-PDT is easy to perform, moderately effective, and safe to use in patients with CHE. Repeated treatments might be required to maintain remission.
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Affiliation(s)
- Noa Kremer
- Photodermatosis Service and Laser Unit, Division of Dermatology, Rabin Medical Center, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Shany Sherman
- Photodermatosis Service and Laser Unit, Division of Dermatology, Rabin Medical Center, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Moshe Lapidoth
- Photodermatosis Service and Laser Unit, Division of Dermatology, Rabin Medical Center, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Claes D Enk
- Department of Dermatology, Hadassah-Hebrew University Medical School, Jerusalem, Israel
| | - Yael Anne Leshem
- Photodermatosis Service and Laser Unit, Division of Dermatology, Rabin Medical Center, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Tomer Mimouni
- Photodermatosis Service and Laser Unit, Division of Dermatology, Rabin Medical Center, Petah Tikva, Israel
| | - Dean Dudkiewicz
- Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Emmilia Hodak
- Photodermatosis Service and Laser Unit, Division of Dermatology, Rabin Medical Center, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Assi Levi
- Photodermatosis Service and Laser Unit, Division of Dermatology, Rabin Medical Center, Petah Tikva, Israel.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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22
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Pinart M, Rueda JR, Romero GA, Pinzón-Flórez CE, Osorio-Arango K, Silveira Maia-Elkhoury AN, Reveiz L, Elias VM, Tweed JA. Interventions for American cutaneous and mucocutaneous leishmaniasis. Cochrane Database Syst Rev 2020; 8:CD004834. [PMID: 32853410 PMCID: PMC8094931 DOI: 10.1002/14651858.cd004834.pub3] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
BACKGROUND On the American continent, cutaneous and mucocutaneous leishmaniasis (CL and MCL) are diseases associated with infection by several species of Leishmania parasites. Pentavalent antimonials remain the first-choice treatment. There are alternative interventions, but reviewing their effectiveness and safety is important as availability is limited. This is an update of a Cochrane Review first published in 2009. OBJECTIVES To assess the effects of interventions for all immuno-competent people who have American cutaneous and mucocutaneous leishmaniasis (ACML). SEARCH METHODS We updated our database searches of the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, LILACS and CINAHL to August 2019. We searched five trials registers. SELECTION CRITERIA Randomised controlled trials (RCTs) assessing either single or combination treatments for ACML in immuno-competent people, diagnosed by clinical presentation and Leishmania infection confirmed by smear, culture, histology, or polymerase chain reaction on a biopsy specimen. The comparators were either no treatment, placebo only, or another active compound. DATA COLLECTION AND ANALYSIS We used standard methodological procedures expected by Cochrane. Our key outcomes were the percentage of participants 'cured' at least three months after the end of treatment, adverse effects, and recurrence. We used GRADE to assess evidence certainty for each outcome. MAIN RESULTS We included 75 studies (37 were new), totalling 6533 randomised participants with ATL. The studies were mainly conducted in Central and South America at regional hospitals, local healthcare clinics, and research centres. More male participants were included (mean age: roughly 28.9 years (SD: 7.0)). The most common confirmed species were L. braziliensis, L. panamensis, and L. mexicana. The most assessed interventions and comparators were non-antimonial systemics (particularly oral miltefosine) and antimonials (particularly meglumine antimoniate (MA), which was also a common intervention), respectively. Three studies included moderate-to-severe cases of mucosal leishmaniasis but none included cases with diffuse cutaneous or disseminated CL, considered the severe cutaneous form. Lesions were mainly ulcerative and located in the extremities and limbs. The follow-up (FU) period ranged from 28 days to 7 years. All studies had high or unclear risk of bias in at least one domain (especially performance bias). None of the studies reported the degree of functional or aesthetic impairment, scarring, or quality of life. Compared to placebo, at one-year FU, intramuscular (IM) MA given for 20 days to treat L. braziliensis and L. panamensis infections in ACML may increase the likelihood of complete cure (risk ratio (RR) 4.23, 95% confidence interval (CI) 0.84 to 21.38; 2 RCTs, 157 participants; moderate-certainty evidence), but may also make little to no difference, since the 95% CI includes the possibility of both increased and reduced healing (cure rates), and IMMA probably increases severe adverse effects such as myalgias and arthralgias (RR 1.51, 95% CI 1.17 to 1.96; 1 RCT, 134 participants; moderate-certainty evidence). IMMA may make little to no difference to the recurrence risk, but the 95% CI includes the possibility of both increased and reduced risk (RR 1.79, 95% CI 0.17 to 19.26; 1 RCT, 127 participants; low-certainty evidence). Compared to placebo, at six-month FU, oral miltefosine given for 28 days to treat L. mexicana, L. panamensis and L. braziliensis infections in American cutaneous leishmaniasis (ACL) probably improves the likelihood of complete cure (RR 2.25, 95% CI 1.42 to 3.38), and probably increases nausea rates (RR 3.96, 95% CI 1.49 to 10.48) and vomiting (RR 6.92, 95% CI 2.68 to 17.86) (moderate-certainty evidence). Oral miltefosine may make little to no difference to the recurrence risk (RR 2.97, 95% CI 0.37 to 23.89; low-certainty evidence), but the 95% CI includes the possibility of both increased and reduced risk (all based on 1 RCT, 133 participants). Compared to IMMA, at 6 to 12 months FU, oral miltefosine given for 28 days to treat L. braziliensis, L. panamensis, L. guyanensis and L. amazonensis infections in ACML may make little to no difference to the likelihood of complete cure (RR 1.05, 95% CI 0.90 to 1.23; 7 RCTs, 676 participants; low-certainty evidence). Based on moderate-certainty evidence (3 RCTs, 464 participants), miltefosine probably increases nausea rates (RR 2.45, 95% CI 1.72 to 3.49) and vomiting (RR 4.76, 95% CI 1.82 to 12.46) compared to IMMA. Recurrence risk was not reported. For the rest of the key comparisons, recurrence risk was not reported, and risk of adverse events could not be estimated. Compared to IMMA, at 6 to 12 months FU, oral azithromycin given for 20 to 28 days to treat L. braziliensis infections in ACML probably reduces the likelihood of complete cure (RR 0.51, 95% CI 0.34 to 0.76; 2 RCTs, 93 participants; moderate-certainty evidence). Compared to intravenous MA (IVMA) and placebo, at 12 month FU, adding topical imiquimod to IVMA, given for 20 days to treat L. braziliensis, L. guyanensis and L. peruviana infections in ACL probably makes little to no difference to the likelihood of complete cure (RR 1.30, 95% CI 0.95 to 1.80; 1 RCT, 80 participants; moderate-certainty evidence). Compared to MA, at 6 months FU, one session of local thermotherapy to treat L. panamensis and L. braziliensis infections in ACL reduces the likelihood of complete cure (RR 0.80, 95% CI 0.68 to 0.95; 1 RCT, 292 participants; high-certainty evidence). Compared to IMMA and placebo, at 26 weeks FU, adding oral pentoxifylline to IMMA to treat CL (species not stated) probably makes little to no difference to the likelihood of complete cure (RR 0.86, 95% CI 0.63 to 1.18; 1 RCT, 70 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS Evidence certainty was mostly moderate or low, due to methodological shortcomings, which precluded conclusive results. Overall, both IMMA and oral miltefosine probably result in an increase in cure rates, and nausea and vomiting are probably more common with miltefosine than with IMMA. Future trials should investigate interventions for mucosal leishmaniasis and evaluate recurrence rates of cutaneous leishmaniasis and its progression to mucosal disease.
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Affiliation(s)
- Mariona Pinart
- Free time independent Cochrane reviewer, Berlin, Germany
| | - José-Ramón Rueda
- Department of Preventive Medicine and Public Health, University of the Basque Country, Leioa, Spain
| | - Gustavo As Romero
- Center for Tropical Medicine, University of Brasilia, Brasilia, Brazil
| | | | - Karime Osorio-Arango
- Dirección de Redes en Salud Pública, Instituto Nacional de Salud, Bogotá, Colombia
| | - Ana Nilce Silveira Maia-Elkhoury
- Communicable Diseases and Environmental Determinants of Health (CDE), Neglected, Tropical and Vector Borne Diseases (VT), Pan American Health Organization/ World Health Organization (PAHO/WHO), Rio de Janeiro, Brazil
| | - Ludovic Reveiz
- Evidence and Intelligence for Action in Health Department, Pan American Health Organization (PAHO), Washington DC, USA
| | - Vanessa M Elias
- Evidence and Intelligence for Action in Health Department, Pan American Health Organization (PAHO), Washington DC, USA
| | - John A Tweed
- c/o Cochrane Skin Group, The University of Nottingham, Nottingham, UK
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Goldin H, Kohen S, Taxy J, Libman M, Cibull T, Billick K. Leishmania tropica infection of the ear treated with photodynamic therapy. JAAD Case Rep 2020; 6:514-517. [PMID: 32490113 PMCID: PMC7256222 DOI: 10.1016/j.jdcr.2020.03.014] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
Affiliation(s)
- Harry Goldin
- Goldin Skin Dermatology and Dermatologic Surgery, Skokie, Illinois
| | - Scott Kohen
- Aureus University School of Medicine, Aureus, Aruba
| | - Jerome Taxy
- Department of Pathology, Northshore Universtity Hospital, Evanston, Illinois
| | - Michael Libman
- Department of Medicine, Division of Infectious Diseases, McGill University, Montreal, Canada
| | - Thomas Cibull
- Department of Pathology, Northshore Universtity Hospital, Evanston, Illinois
| | - Kendall Billick
- Department of Dermatology, McGill University, Montreal, Canada
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Radunz S, Wedepohl S, Röhr M, Calderón M, Tschiche HR, Resch-Genger U. pH-Activatable Singlet Oxygen-Generating Boron-dipyrromethenes (BODIPYs) for Photodynamic Therapy and Bioimaging. J Med Chem 2020; 63:1699-1708. [DOI: 10.1021/acs.jmedchem.9b01873] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Affiliation(s)
- Sebastian Radunz
- Division Biophotonics, Federal Institute for Materials Research and Testing (BAM), Richard-Willstaetter-Str. 11, 12489 Berlin, Germany
| | - Stefanie Wedepohl
- Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany
| | - Mathilde Röhr
- Division Biophotonics, Federal Institute for Materials Research and Testing (BAM), Richard-Willstaetter-Str. 11, 12489 Berlin, Germany
| | - Marcelo Calderón
- Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany
- POLYMAT and Applied Chemistry Department, Faculty of Chemistry, University of the Basque Country UPV/EHU, Paseo Manuel de Lardizabal 3, 20018 Donostia-San Sebastián, Spain
- Basque Foundation for Science, Ikerbasque, 48013 Bilbao, Spain
| | - Harald Rune Tschiche
- Department of Chemical and Product Safety, German Federal Institute for Risk Assessment (BfR), Max-Dohrn-Str. 8-10, 10589 Berlin, Germany
| | - Ute Resch-Genger
- Division Biophotonics, Federal Institute for Materials Research and Testing (BAM), Richard-Willstaetter-Str. 11, 12489 Berlin, Germany
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25
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Cabral FV, Sabino CP, Dimmer JA, Sauter IP, Cortez MJ, Ribeiro MS. Preclinical Investigation of Methylene Blue‐mediated Antimicrobial Photodynamic Therapy on
Leishmania
Parasites Using Real‐Time Bioluminescence. Photochem Photobiol 2019; 96:604-610. [DOI: 10.1111/php.13188] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2019] [Accepted: 11/01/2019] [Indexed: 12/13/2022]
Affiliation(s)
- Fernanda V. Cabral
- Center for Lasers and Applications, Nuclear and Energy Research Institute (IPEN‐CNEN/SP) São Paulo SP Brazil
| | - Caetano P. Sabino
- School of Pharmaceutical Sciences University of São Paulo São Paulo SP Brazil
- Biolambda, Translational Biophotonics LTD São Paulo SP Brazil
| | - Jesica A. Dimmer
- Pharmaceutical Sciences Department School of Chemical Sciences National University of Córdoba Córdoba Argentina
- Multidisciplinary Institute of Plant Biology (IMBIV) CONICET Córdoba Argentina
| | - Ismael P. Sauter
- Center for Lasers and Applications, Nuclear and Energy Research Institute (IPEN‐CNEN/SP) São Paulo SP Brazil
| | - Mauro J. Cortez
- Institute of Biosciences University of São Paulo (ICB/USP) São Paulo SP Brazil
| | - Martha S. Ribeiro
- Center for Lasers and Applications, Nuclear and Energy Research Institute (IPEN‐CNEN/SP) São Paulo SP Brazil
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26
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Morton CA, Szeimies RM, Basset-Séguin N, Calzavara-Pinton PG, Gilaberte Y, Haedersdal M, Hofbauer GFL, Hunger RE, Karrer S, Piaserico S, Ulrich C, Wennberg AM, Braathen LR. European Dermatology Forum guidelines on topical photodynamic therapy 2019 Part 2: emerging indications - field cancerization, photorejuvenation and inflammatory/infective dermatoses. J Eur Acad Dermatol Venereol 2019; 34:17-29. [PMID: 31805604 DOI: 10.1111/jdv.16044] [Citation(s) in RCA: 87] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2019] [Accepted: 10/24/2019] [Indexed: 12/12/2022]
Abstract
In addition to approved indications in non-melanoma skin cancer in immunocompetent patients, topical photodynamic therapy (PDT) has also been studied for its place in the treatment of, as well as its potential to prevent, superficial skin cancers in immune-suppressed patients, although sustained clearance rates are lower than for immune-competent individuals. PDT using a nanoemulsion of ALA in a daylight or conventional PDT protocol has been approved for use in field cancerization, although evidence of the potential of the treatment to prevent new SCC remained limited. High-quality evidence supports a strong recommendation for the use of topical PDT in photorejuvenation as well as for acne, refractory warts, cutaneous leishmaniasis and in onychomycosis, although these indications currently lack approvals for use and protocols remain to be optimized, with more comparative evidence with established therapies required to establish its place in practice. Adverse events across all indications for PDT can be minimized through the use of modified and low-irradiance regimens, with a low risk of contact allergy to photosensitizer prodrugs, and no other significant documented longer-term risks with no current evidence of cumulative toxicity or photocarcinogenic risk. The literature on the pharmacoeconomics for using PDT is also reviewed, although accurate comparisons are difficult to establish in different healthcare settings, comparing hospital/office-based therapies of PDT and surgery with topical ointments, requiring inclusion of number of visits, real-world efficacy as well as considering the value to be placed on cosmetic outcome and patient preference. This guideline, published over two parts, considers all current approved and emerging indications for the use of topical photodynamic therapy in Dermatology prepared by the PDT subgroup of the European Dermatology Forum guidelines committee. It presents consensual expert recommendations reflecting current published evidence.
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Affiliation(s)
- C A Morton
- Department of Dermatology, Stirling Community Hospital, Stirling, UK
| | - R-M Szeimies
- Department of Dermatology, Regensburg University Hospital, Regensburg, Germany.,Department of Dermatology & Allergology, Klinikum Vest GmbH, Recklinghausen, Germany
| | - N Basset-Séguin
- Department of Dermatology, Hôpital Saint Louis, Paris, France
| | | | - Y Gilaberte
- Department of Dermatology, Hospital Universitario miguel servet IIS Aragón, Zaragoza, Spain
| | - M Haedersdal
- Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark
| | - G F L Hofbauer
- Department of Dermatology, Zürich University Hospital, Zürich, Switzerland
| | - R E Hunger
- Department of Dermatology Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
| | - S Karrer
- Department of Dermatology, Regensburg University Hospital, Regensburg, Germany
| | - S Piaserico
- Unit of Dermatology, Department of Medicine, University of Padova, Padova, Italy
| | - C Ulrich
- Skin Cancer Centre, Charité Universitätsmedizin Berlin, Berlin, Germany
| | - A-M Wennberg
- Department of Dermatology, Sahlgrenska University Hospital, Gothenburg, Sweden
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Zhao W, Shan XF, Wang CL, Liu XZ, Li Z, Xiao HL, Li ZW, Zheng RT, Hou JL, Tian HQ. Topical 5-aminolevulinic acid photodynamic therapy for intra anal-rectal warts. J DERMATOL TREAT 2019; 31:241-244. [PMID: 30990345 DOI: 10.1080/09546634.2019.1594670] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Background: Condylomata acuminata (CA) are a common sexually transmitted disease. The recurrence rate of condyloma acuminatum using traditional treatments is higher than that of applying photodynamic therapy, and a variety of adverse reactions after treatment. At the same time, different parts of condyloma acuminatum after treatment recurrence rate is also different, especially for intra anal-rectal warts.Objective: To evaluate whether using photodynamic therapy (PDT) can effectively reduce recurrence of condylomata acuminata for intra anal-rectal warts.Methods: After the confirmation of the diagnosis of intra anal-rectal warts, the patients were treated with PDT with 5-aminolevulinic acid hydrochloride (ALA). PDT was performed with irradiation of 18-36 J/cm2 at an irradiance of 20-40 mW/cm2 with light-emitting diode (LED) light energy, wavelength 635 nm. We used a special PDT light equipment for intra anal-rectal area warts. PDT was repeated once every week for 4 weeks.Results: After PDT, the complete clearance rate was 76.1% (35 of 46 patients). At the end of the 12 weeks followed, recurrence occurred in five cases. We recorded pain in all 46 patients and the average visual analog scale (VAS) pain score was 6.96 ± 1.41 points.Conclusion: The treatment with PDT is effective in reducing the high rate of recurrence for intra anal-rectal warts. Pain is still a great challenge for the therapy.
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Affiliation(s)
- Wei Zhao
- Shandong Provincial Institute of Dermatology and Venereology, Shandong, China
| | - Xiao-Feng Shan
- Shandong Provincial Institute of Dermatology and Venereology, Shandong, China
| | - Chang-Liang Wang
- Shandong Provincial Institute of Dermatology and Venereology, Shandong, China
| | - Xin-Zhou Liu
- Shandong Provincial Institute of Dermatology and Venereology, Shandong, China
| | - Zhen Li
- Shandong Provincial Institute of Dermatology and Venereology, Shandong, China
| | - Hai-Lu Xiao
- Jining Medical College Affiliated Hospital of Jining Medical University, Jining, China
| | - Zhong-Wei Li
- Shandong Provincial Institute of Dermatology and Venereology, Shandong, China
| | - Rong-Tao Zheng
- Shandong Provincial Institute of Dermatology and Venereology, Shandong, China
| | - Jian-Ling Hou
- Shandong Provincial Institute of Dermatology and Venereology, Shandong, China
| | - Hong-Qing Tian
- Shandong Provincial Institute of Dermatology and Venereology, Shandong, China
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28
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Johansen MB, Jemec GB, Fabricius S. Effective treatment with photodynamic therapy of cutaneous leishmaniasis: A case report. Dermatol Ther 2019; 32:e13022. [DOI: 10.1111/dth.13022] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2018] [Revised: 07/04/2019] [Accepted: 07/11/2019] [Indexed: 12/22/2022]
Affiliation(s)
| | - Gregor B.E. Jemec
- Department of DermatologyZealand University Hospital Roskilde Denmark
| | - Susanne Fabricius
- Department of DermatologyZealand University Hospital Roskilde Denmark
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29
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Nguyen K, Khachemoune A. An update on topical photodynamic therapy for clinical dermatologists. J DERMATOL TREAT 2019; 30:732-744. [DOI: 10.1080/09546634.2019.1569752] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Affiliation(s)
- Khoa Nguyen
- College of Medicine, University of Central Florida, Orlando, FL, USA
| | - Amor Khachemoune
- Veterans Affairs Medical Center, Brooklyn, NY, USA
- Department of Dermatology, SUNY Downstate, Brooklyn, NY, USA
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30
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Sainz-Gaspar L, Rosón E, Llovo J, Vázquez-Veiga H. Photodynamic Therapy in the Treatment of Cutaneous Leishmaniasis. ACTAS DERMO-SIFILIOGRAFICAS 2019. [DOI: 10.1016/j.adengl.2019.02.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
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31
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Szeimïes RM. Pain perception during photodynamic therapy: why is daylight PDT with methyl aminolevulinate almost pain-free? A review on the underlying mechanisms, clinical reflections and resulting opportunities. GIORN ITAL DERMAT V 2018; 153:793-799. [DOI: 10.23736/s0392-0488.18.06011-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/16/2023]
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32
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Lechuga GC, Pereira MCS, Bourguignon SC. Heme metabolism as a therapeutic target against protozoan parasites. J Drug Target 2018; 27:767-779. [DOI: 10.1080/1061186x.2018.1536982] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Affiliation(s)
- Guilherme Curty Lechuga
- Laboratório de Interação celular e molecular, Departamento de Biologia Celular e Molecular, Universidade Federal Fluminense, Rua Outeiro São João Batista, Rio de Janeiro, Brazil
- Fundação Oswaldo Cruz, Laboratório de Ultraestrutura Celular, Rio de Janeiro, Brazil
- Instituto de Biologia, Programa de Pós-graduação em Ciências e Biotecnologia (PPBI), Universidade Federal Fluminense, Rio de Janeiro, Brazil
| | - Mirian C. S. Pereira
- Fundação Oswaldo Cruz, Laboratório de Ultraestrutura Celular, Rio de Janeiro, Brazil
| | - Saulo C. Bourguignon
- Laboratório de Interação celular e molecular, Departamento de Biologia Celular e Molecular, Universidade Federal Fluminense, Rua Outeiro São João Batista, Rio de Janeiro, Brazil
- Instituto de Biologia, Programa de Pós-graduação em Ciências e Biotecnologia (PPBI), Universidade Federal Fluminense, Rio de Janeiro, Brazil
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Abstract
Topical photodynamic therapy (PDT) using daylight is effective in the treatment of actinic keratoses (AKs), offering the potential for treatment of large fields such as full face and balding scalp, but with minimal therapy-associated pain. Comparison with conventional PDT indicates similar efficacy for thin and moderate-thickness AKs, but with significantly less discomfort/pain, driving a patient preference for daylight-mediated PDT (DL-PDT) compared with conventional PDT using high-intensity office/hospital-based light sources. Treatment protocol involves the application of a photosensitizing agent without occlusion and subsequent exposure to ambient daylight within 30 min, with patients exposed to daylight for 1.5-2.0 h. Pivotal randomized controlled trials in Europe and Australia have confirmed the efficacy of methyl aminolevulinic acid (MAL) DL-PDT in comparison with conventional MAL-PDT for mild and moderate-thickness lesions on the face and scalp. Initial clearance rates of 70-89% are reported. DL-PDT using a nanoemulsion aminolevulinic acid (ALA) has recently been shown to be at least as effective as MAL DL-PDT in treating mild and moderate-thickness AKs. DL-PDT may offer a better-tolerated method for treating patients with extensive AK disease. There is emerging literature on the potential for field PDT to reduce the number of new AKs developing, potentially preventing/slowing skin cancer development. Conventional PDT remains established as a therapy for Bowen's disease (squamous cell carcinoma in situ), superficial and certain thin basal cell carcinomas (BCCs), and AKs. The evidence for the use of DL-PDT beyond AK is limited, although has been reported in actinic cheilitis, superficial BCC, and acne and cutaneous leishmaniasis. There is emerging interest in combination therapy for AK, using one or more field therapies such as DL-PDT as an option to complement with localized treatment for residual lesions. We review current recommendations and consider the appropriate place for DL-PDT in our treatment armamentarium.
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34
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Photodynamic Therapy in the Treatment of Cutaneous Leishmaniasis. ACTAS DERMO-SIFILIOGRAFICAS 2018; 110:249-251. [PMID: 29961547 DOI: 10.1016/j.ad.2018.02.018] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2017] [Revised: 01/25/2018] [Accepted: 02/05/2018] [Indexed: 11/23/2022] Open
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35
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Pérez-Laguna V, García-Malinis AJ, Aspiroz C, Rezusta A, Gilaberte Y. Antimicrobial effects of photodynamic therapy. GIORN ITAL DERMAT V 2018; 153:833-846. [PMID: 29683289 DOI: 10.23736/s0392-0488.18.06007-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
The microorganisms that cause infections are increasing their resistance to antibiotics. In this context, alternative treatments are necessary. The antimicrobial photodynamic therapy (aPDT) is a therapeutic modality based on photosensitizing molecules that end up generating reactive oxygen species that induce the destruction of the target cells when are irradiated with light of a suitable wavelength and at a proper dose. The cells targeted by aPDT are all types of microorganisms (bacteria, fungi and parasites) including viruses and has been proven effective against representative members of all of them. In the field of dermatology, aPDT has been tested with promising results in different infections such as chronic ulcers, acne, onychomycosis and other cutaneous mycoses, as well as in leishmaniasis. Therefore, it is presented as a possible treatment option against the agents that cause skin and/or mucous infections.
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Affiliation(s)
| | | | - Carmen Aspiroz
- Unit of Microbiology, Hospital Royo Villanova, Zaragoza, Spain
| | - Antonio Rezusta
- IIS Aragón, Zaragoza, Spain.,Department of Microbiology, Hospital Universitario Miguel Servet, Zaragoza, Spain
| | - Yolanda Gilaberte
- IIS Aragón, Zaragoza, Spain - .,Department of Dermatology, Hospital Universitario Miguel Servet, Zaragoza, Spain
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36
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Viana SM, Celes FS, Ramirez L, Kolli B, Ng DKP, Chang KP, de Oliveira CI. Photodynamic Vaccination of BALB/c Mice for Prophylaxis of Cutaneous Leishmaniasis Caused by Leishmania amazonensis. Front Microbiol 2018; 9:165. [PMID: 29467751 PMCID: PMC5808246 DOI: 10.3389/fmicb.2018.00165] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2017] [Accepted: 01/24/2018] [Indexed: 11/26/2022] Open
Abstract
Background: Photosensitizers (PS), like porphyrins and phthalocyanines (PC) are excitable by light to generate cytotoxic singlet oxygen and other reactive oxygen species in the presence of atmospheric O2. Photodynamic inactivation of Leishmania by this means renders them non-viable, but preserves their effective use as vaccines. Leishmania can be photo-inactivated after PS-sensitization by loading via their endocytic uptake of PC or endogenous induction of transgenic mutants with delta-aminolevulinate (ALA) to accumulate cytosolic uroporphyrin I (URO). Here, PS-sensitization and photo-inactivation of Leishmaniaamazonensis was further examined in vitro and in vivo for vaccination against cutaneous leishmaniasis (CL). Methods and Results:Leishmania amazonensis promastigotes were photodynamically inactivated in vitro by PC-loading followed by exposure to red light (1–2 J/cm2) or ALA-induction of uroporphyrinogenic transfectants to accumulate cytosolic URO followed by longwave UV exposure. When applied individually, both strategies of photodynamic inactivation were found to significantly, albeit incompletely abolish the MTT reduction activities of the promastigotes, their uptake by mouse bone marrow-derived macrophages in vitro and their infectivity to mouse ear dermis in vivo. Inactivation of Leishmania to completion by using a combination of both strategies was thus used for the sake of safety as whole-cell vaccines for immunization of BALB/c mice. Different cutaneous sites were assessed for the efficacy of such photodynamic vaccination in vivo. Each site was inoculated first with in vitro doubly PS-sensitized promastigotes and then spot-illuminated with white light (50 J/cm2) for their photo-inactivation in situ. Only in ear dermis parasites were photo-inactivated beyond detection. Mice were thus immunized once in the ear and challenged 3 weeks later at the tail base with virulent L. amazonensis. Prophylaxis was noted in mice photodynamically vaccinated with doubly photo-inactivated parasites, as indicated by a significant delay in the onset of lesion development and a substantial decrease in the parasite loads. Conclusion: Leishmania doubly PS-sensitized and in situ photo-inactivated as described proved to be safe and effective when used for one-time immunization of ear dermis, as indicated by its significant protection of the inherently very susceptible BALB/c mice against CL.
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Affiliation(s)
| | | | - Laura Ramirez
- Instituto Gonçalo Muniz (IGM), FIOCRUZ, Salvador, Brazil
| | - Bala Kolli
- Department of Microbiology/Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, United States
| | - Dennis K P Ng
- Department of Chemistry, The Chinese University of Hong Kong, Hong Kong, Hong Kong
| | - Kwang P Chang
- Department of Microbiology/Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, United States
| | - Camila I de Oliveira
- Instituto Gonçalo Muniz (IGM), FIOCRUZ, Salvador, Brazil.,Instituto Nacional de Ciência e Tecnologia (iii-INCT) - Instituto de Investigação em Imunologia, São Paulo, Brazil
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37
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García-Malinis A, Milagro Beamonte A, Torres Sopena L, García-Callen O, Puertolas-Villacampa P, Gilaberte Y. Cutaneous sporotrichosis treated with methylene blue-daylight photodynamic therapy. J Eur Acad Dermatol Venereol 2017; 32:e90-e91. [DOI: 10.1111/jdv.14545] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Affiliation(s)
- A.J. García-Malinis
- Unit of Dermatology; San Jorge Hospital; Avenida Martinez de Velasco, 36 Huesca Spain
- Unit of Dermatology; Jaca Hospital; Avenida Rapitan sn, Jaca Huesca Spain
| | - A. Milagro Beamonte
- Department of Microbiology; San Jorge Hospital; Avenida Martínez de Velasco, 36 Huesca Spain
| | - L. Torres Sopena
- Department of Microbiology; San Jorge Hospital; Avenida Martínez de Velasco, 36 Huesca Spain
| | - O. García-Callen
- Unit of Dermatology; Jaca Hospital; Avenida Rapitan sn, Jaca Huesca Spain
| | | | - Y. Gilaberte
- Unit of Dermatology; San Jorge Hospital; Avenida Martinez de Velasco, 36 Huesca Spain
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38
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Dichiara M, Marrazzo A, Prezzavento O, Collina S, Rescifina A, Amata E. Repurposing of Human Kinase Inhibitors in Neglected Protozoan Diseases. ChemMedChem 2017; 12:1235-1253. [PMID: 28590590 DOI: 10.1002/cmdc.201700259] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2017] [Indexed: 12/11/2022]
Abstract
Human African trypanosomiasis (HAT), Chagas disease, and leishmaniasis belong to a group of infectious diseases known as neglected tropical diseases and are induced by infection with protozoan parasites named trypanosomatids. Drugs in current use have several limitations, and therefore new candidate drugs are required. The majority of current therapeutic trypanosomatid targets are enzymes or cell-surface receptors. Among these, eukaryotic protein kinases are a major group of protein targets whose modulation may be beneficial for the treatment of neglected tropical protozoan diseases. This review summarizes the finding of new hit compounds for neglected tropical protozoan diseases, by repurposing known human kinase inhibitors on trypanosomatids. Kinase inhibitors are grouped by human kinase family and discussed according to the screening (target-based or phenotypic) reported for these compounds on trypanosomatids. This collection aims to provide insight into repurposed human kinase inhibitors and their importance in the development of new chemical entities with potential beneficial effects on the diseases caused by trypanosomatids.
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Affiliation(s)
- Maria Dichiara
- Department of Drug Sciences, University of Catania, V.le A. Doria, 6, 95100, Catania, Italy
| | - Agostino Marrazzo
- Department of Drug Sciences, University of Catania, V.le A. Doria, 6, 95100, Catania, Italy
| | - Orazio Prezzavento
- Department of Drug Sciences, University of Catania, V.le A. Doria, 6, 95100, Catania, Italy
| | - Simona Collina
- Department of Drug Sciences, University of Pavia, V.le Taramelli, 12, 27100, Pavia, Italy
| | - Antonio Rescifina
- Department of Drug Sciences, University of Catania, V.le A. Doria, 6, 95100, Catania, Italy
| | - Emanuele Amata
- Department of Drug Sciences, University of Catania, V.le A. Doria, 6, 95100, Catania, Italy
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Pérez-Laguna V, Pérez-Artiaga L, Lampaya-Pérez V, García-Luque I, Ballesta S, Nonell S, Paz-Cristobal MP, Gilaberte Y, Rezusta A. Bactericidal Effect of Photodynamic Therapy, Alone or in Combination with Mupirocin or Linezolid, on Staphylococcus aureus. Front Microbiol 2017. [PMID: 28626456 PMCID: PMC5454219 DOI: 10.3389/fmicb.2017.01002] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Antibiotic treatments frequently fail due to the development of antibiotic resistance, underscoring the need for new treatment strategies. Antimicrobial photodynamic therapy (aPDT) could constitute an alternative therapy. In bacterial suspensions of Staphylococcus aureus, which is commonly implicated in cutaneous and mucosal infections, we evaluated the in vitro efficacy of aPDT, using the photosensitizing agents rose bengal (RB) or methylene blue (MB), alone or combined with the antibiotics mupirocin (MU) or linezolid (LN). RB or MB, at concentrations ranging from 0.03 to 10 μg/ml, were added to S. aureus ATCC 29213 suspensions containing >108 cells/ml, in the absence or presence of MU or LN (1 or 10 μg/ml). Suspensions were irradiated with a white metal halide (λ 420–700 nm) or light-emitting diode lamp (λ 515 and λ 625 nm), and the number of viable bacteria quantified by counting colony-forming units (CFU) on blood agar. Addition of either antibiotic had no significant effect on the number of CFU/ml. By contrast, RB-aPDT and MB-aPDT effectively inactivated S. aureus, as evidenced by a 6 log10 reduction in bacterial growth. In the presence of MU or LN, the same 6 log10 reduction was observed in response to aPDT, but was achieved using significantly lower concentrations of the photosensitizers RB or MB. In conclusion, the combination of MU or LN and RB/MB-aPDT appears to exert a synergistic bactericidal effect against S. aureus in vitro.
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Affiliation(s)
- Vanesa Pérez-Laguna
- IIS AragónZaragoza, Spain.,Department of Microbiology, Hospital Universitario Miguel ServetZaragoza, Spain
| | - Luna Pérez-Artiaga
- Department of Microbiology, Hospital Universitario Miguel ServetZaragoza, Spain
| | | | | | - Sofía Ballesta
- Department of Microbiology, University of SevillaSeville, Spain
| | - Santi Nonell
- Institut Químic de Sarrià, Universitat Ramon LlullBarcelona, Spain
| | | | - Yolanda Gilaberte
- IIS AragónZaragoza, Spain.,Department of Dermatology, Hospital San JorgeHuesca, Spain
| | - Antonio Rezusta
- IIS AragónZaragoza, Spain.,Department of Microbiology, Hospital Universitario Miguel ServetZaragoza, Spain.,Department of Microbiology, Preventive Medicine and Public Health, University of ZaragozaZaragoza, Spain
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40
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Safety and efficacy of current alternatives in the topical treatment of cutaneous leishmaniasis: a systematic review. Parasitology 2017; 144:995-1004. [DOI: 10.1017/s0031182017000385] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
SUMMARYStudies of topical treatments for leishmaniasis were systematically reviewed, to evaluate the therapeutic efficacy, safety and any adverse effects of these treatments. The papers identified in the databases PubMed and Web of Knowledge involved eight studies with a total of 1744 patients. The majority of trials was from Iran (4/8), covered a period of 8 years (2003–2011), and included patients 4–85 years of age. The most frequent Leishmania species in the studies were L. tropica (4/8) and L. major (2/8). The treatments administered were thermotherapy, paromomycin and combinations, CO2 laser, 5-aminolevulinic acid hydrochloride (10%) plus visible red light (633 nm) and cryotherapy. Six articles reported cure rates over 80·0%. Six studies reported on failure rates, three of them reporting rates lower than 10%. Four studies did not report relapses or recurrences, while the other studies reported low rates (1·8–6·3%). The most common adverse effects of the topical treatments were redness/erythema, pain, pruritus burning, oedema, vesicles and hyper- or hypopigmentation. The results provide strong evidence that the treatments topical evaluated showed high cure rates, safety and effectiveness, with low side-effects, relapse and recurrence rates, except for cryotherapy, which showed a moderate cure rate.
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41
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Aronson N, Herwaldt BL, Libman M, Pearson R, Lopez-Velez R, Weina P, Carvalho EM, Ephros M, Jeronimo S, Magill A. Diagnosis and Treatment of Leishmaniasis: Clinical Practice Guidelines by the Infectious Diseases Society of America (IDSA) and the American Society of Tropical Medicine and Hygiene (ASTMH). Clin Infect Dis 2016; 63:e202-e264. [PMID: 27941151 DOI: 10.1093/cid/ciw670] [Citation(s) in RCA: 190] [Impact Index Per Article: 21.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2016] [Accepted: 09/22/2016] [Indexed: 12/25/2022] Open
Abstract
It is important to realize that leishmaniasis guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. The IDSA and ASTMH consider adherence to these guidelines to be voluntary, with the ultimate determinations regarding their application to be made by the physician in the light of each patient's individual circumstances.
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Affiliation(s)
- Naomi Aronson
- Uniformed Services University of the Health Sciences, Bethesda, Maryland
| | | | - Michael Libman
- McGill University Health Centre, Montreal, Quebec, Canada
| | | | | | - Peter Weina
- Walter Reed National Military Medical Center, Bethesda, Maryland
| | | | | | - Selma Jeronimo
- Federal University of Rio Grande do Norte, Natal, Brazil
| | - Alan Magill
- Bill and Melinda Gates Foundation, Seattle, Washington
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42
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Pinto JG, Fontana LC, de Oliveira MA, Kurachi C, Raniero LJ, Ferreira-Strixino J. In vitro evaluation of photodynamic therapy using curcumin on Leishmania major and Leishmania braziliensis. Lasers Med Sci 2016; 31:883-90. [DOI: 10.1007/s10103-016-1928-5] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2015] [Accepted: 03/18/2016] [Indexed: 12/17/2022]
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Aminophthalocyanine-Mediated Photodynamic Inactivation of Leishmania tropica. Antimicrob Agents Chemother 2016; 60:2003-11. [PMID: 26824938 DOI: 10.1128/aac.01879-15] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2015] [Accepted: 01/04/2016] [Indexed: 01/29/2023] Open
Abstract
Photodynamic inactivation ofLeishmaniaspp. requires the cellular uptake of photosensitizers, e.g., endocytosis of silicon(IV)-phthalocyanines (PC) axially substituted with bulky ligands. We report here that when substituted with amino-containing ligands, the PCs (PC1 and PC2) were endocytosed and displayed improved potency againstLeishmania tropicapromastigotes and axenic amastigotesin vitro The uptake of these PCs by bothLeishmaniastages followed saturation kinetics, as expected. Sensitive assays were developed for assessing the photodynamic inactivation ofLeishmaniaspp. by rendering them fluorescent in two ways: transfecting promastigotes to express green fluorescent protein (GFP) and loading them with carboxyfluorescein succinimidyl ester (CFSE). PC-sensitizedLeishmania tropicastrains were seen microscopically to lose their motility, structural integrity, and GFP/CFSE fluorescence after exposure to red light (wavelength, ∼650 nm) at a fluence of 1 to 2 J cm(-2) Quantitative fluorescence assays based on the loss of GFP/CFSE from liveLeishmania tropicashowed that PC1 and PC2 dose dependently sensitized both stages for photoinactivation, consistent with the results of a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assay.Leishmania tropicastrains are >100 times more sensitive than their host cells or macrophages to PC1- and PC2-mediated photoinactivation, judging from the estimated 50% effective concentrations (EC50s) of these cells. Axial substitution of the PC with amino groups instead of other ligands appears to increase its leishmanial photolytic activity by up to 40-fold. PC1 and PC2 are thus potentially useful for photodynamic therapy of leishmaniasis and for oxidative photoinactivation ofLeishmaniaspp. for use as vaccines or vaccine carriers.
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Ameen M. The potential of daylight-activated photodynamic therapy for treating localized forms of cutaneous leishmaniasis in resource-limited settings. Br J Dermatol 2016; 172:1192-3. [PMID: 25963215 DOI: 10.1111/bjd.13810] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Affiliation(s)
- M Ameen
- Department of Dermatology, Royal Free London NHS Foundation Trust, London, NW3 2QG, U.K..
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Monteiro CS, Ferreira DC, Sáfar GAM, Gontijo RN, Fantini C, Martins DCS, Idemori YM, Pinheiro MVB, Krambrock K. Unravelling the mechanisms of reactive oxygen species formation in nanohybrid systems of porphyrins and enriched (6,5) single-walled carbon nanotubes for photosensitization. Phys Chem Chem Phys 2016; 18:20459-65. [DOI: 10.1039/c6cp03366k] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Two different porphyrins inside the exciton volume of a carbon nanotube with charged N either in or out.
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Affiliation(s)
- Camila S. Monteiro
- Departamento de Química
- Instituto de Ciências Exatas
- Universidade Federal de Minas Gerais
- Belo Horizonte-MG
- Brazil
| | - Daniele C. Ferreira
- Departamento de Física
- Instituto de Ciências Exatas
- Universidade Federal de Minas Gerais
- Belo Horizonte-MG
- Brazil
| | - Gustavo A. M. Sáfar
- Departamento de Física
- Instituto de Ciências Exatas
- Universidade Federal de Minas Gerais
- Belo Horizonte-MG
- Brazil
| | - Rafael N. Gontijo
- Departamento de Física
- Instituto de Ciências Exatas
- Universidade Federal de Minas Gerais
- Belo Horizonte-MG
- Brazil
| | - Cristiano Fantini
- Departamento de Física
- Instituto de Ciências Exatas
- Universidade Federal de Minas Gerais
- Belo Horizonte-MG
- Brazil
| | - Dayse C. S. Martins
- Departamento de Química
- Instituto de Ciências Exatas
- Universidade Federal de Minas Gerais
- Belo Horizonte-MG
- Brazil
| | - Ynara M. Idemori
- Departamento de Química
- Instituto de Ciências Exatas
- Universidade Federal de Minas Gerais
- Belo Horizonte-MG
- Brazil
| | - Maurício V. B. Pinheiro
- Departamento de Física
- Instituto de Ciências Exatas
- Universidade Federal de Minas Gerais
- Belo Horizonte-MG
- Brazil
| | - Klaus Krambrock
- Departamento de Física
- Instituto de Ciências Exatas
- Universidade Federal de Minas Gerais
- Belo Horizonte-MG
- Brazil
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Topical PDT in the Treatment of Benign Skin Diseases: Principles and New Applications. Int J Mol Sci 2015; 16:23259-78. [PMID: 26404243 PMCID: PMC4632697 DOI: 10.3390/ijms161023259] [Citation(s) in RCA: 82] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2015] [Revised: 09/21/2015] [Accepted: 09/22/2015] [Indexed: 02/04/2023] Open
Abstract
Photodynamic therapy (PDT) uses a photosensitizer, light energy, and molecular oxygen to cause cell damage. Cells exposed to the photosensitizer are susceptible to destruction upon light absorption because excitation of the photosensitizing agents leads to the production of reactive oxygen species and, subsequently, direct cytotoxicity. Using the intrinsic cellular heme biosynthetic pathway, topical PDT selectively targets abnormal cells, while preserving normal surrounding tissues. This selective cytotoxic effect is the basis for the use of PDT in antitumor treatment. Clinically, PDT is a widely used therapeutic regimen for oncologic skin conditions such as actinic keratosis, squamous cell carcinoma in situ, and basal cell carcinoma. PDT has been shown, under certain circumstances, to stimulate the immune system and produce antibacterial, and/or regenerative effects while protecting cell viability. Thus, it may be useful for treating benign skin conditions. An increasing number of studies support the idea that PDT may be effective for treating acne vulgaris and several other inflammatory/infective skin diseases, including psoriasis, rosacea, viral warts, and aging-related changes. This review provides an overview of the clinical investigations of PDT and discusses each of the essential aspects of the sequence: its mechanism of action, common photosensitizers, light sources, and clinical applications in dermatology. Of the numerous clinical trials of PDT in dermatology, this review focuses on those studies that have reported remarkable therapeutic benefits following topical PDT for benign skin conditions such as acne vulgaris, viral warts, and photorejuvenation without causing severe side effects.
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Weatherhead JE, Woc-Colburn L. Therapeutic options and vaccine development in the treatment of leishmaniasis. World J Pharmacol 2015; 4:210-218. [DOI: 10.5497/wjp.v4.i2.210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2014] [Revised: 01/28/2015] [Accepted: 04/02/2015] [Indexed: 02/07/2023] Open
Abstract
Early treatment of leishmaniasis is critical to achieve cure, prevent psychological and social distress, and prevent transmission of disease. Untreated Leishmaniasis-cutaneous leishmaniasis, mucocutaneous leishmaniasis and visceral leishmaniasis - results in disfiguring scars and high rates of morbidity and mortality in highly endemic regions of the world. However, cure rates with available therapeutics are limited due to cost, therapeutic toxicity and the growing rate of resistance. New therapeutic targets for medications and vaccine development are under investigation to provide improved healing and efficacy for the treatment of Leishmania spp.
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