Adverse effects of topical photodynamic therapy in rosacea - Case report.

Rosacea is a chronic and inflammatory skin condition, with relapses being a common characteristic. Its treatments are based on cosmetics, drugs, and the application of procedures based on high-powered light. Photodynamic Cosmetic Therapy (PCT) combines light, a photosensitizer (PS), and molecular oxygen present in tissues, generating photochemical reactions capable of causing tissue and vascular destruction, stimulating tissue repair. We report a case with an adverse effect caused by applying PCT, using 2 % 5-aminolevulinic acid (ALA 2 %), and irradiated with amber LED light associated with infrared radiation for the control of rosacea. A patient with subtype II rosacea underwent PCT treatment of 3 sessions at 21-day intervals, being evaluated using photographic images and Wood's lamp. In the first session of the therapy, an exacerbated inflammatory process was observed. Such an adverse event is estimated to be as a result of the patient using ointment containing corticosteroids for a short period. With the use of medications, it was possible to recover the appearance of the skin thoroughly, and after 21 days, the treatment sessions were performed again. Despite the complication that affected the patient in this study, positive effects were found after the pharmacological therapeutic measures were adopted.

Randomized controlled trial for evaluation of efficacy and pain during photodynamic therapy for actinic keratosis of face and scalp comparing two irradiation protocols.

BACKGROUND: Pain is a frequent adverse event during photodynamic therapy, which can limit treatment acceptance. This study aimed to evaluate the efficacy and pain during photodynamic therapy with two irradiation protocols in patients with actinic keratosis on the face and scalp. METHODS: In this intra-patient randomized controlled trial, participants were randomly allocated to receive photodynamic therapy with methyl aminolevulinate and red light on the right or left side with protocol 1 (irradiation device in contact with the skin) and protocol 2 (device 3 cm away from the skin). There was a 15-day interval between the protocols. The primary outcome was the frequency of mean intensity of moderate or severe pain during photodynamic therapy. Secondary outcomes were actinic keratosis clearance rate, protoporphyrin IX consumption, participant preference, skin appearance, and adverse events. RESULTS: Forty-one participants were included, yielding 47 and 50 randomized sites for protocols 1 and 2. There was no difference in the frequency of moderate and severe pain, with a relative risk of 1.09 (95% CI 0.70-1.70), p>0.05. An actinic keratosis count reduction >60% was observed in both protocols (p<0.01), with no difference between them. There was no difference in protoporphyrin IX consumption. Most treated sites were of good to excellent quality. There was a greater patient preference for protocol 2 (p<0.01). CONCLUSIONS: The pain intensity was similar between the protocols, and the protocols were equally effective for actinic keratosis clearance, protoporphyrin IX consumption, and improvement in the quality of the treated areas. Both protocols may be considered safe.

A 12-month follow-up split-scalp study comparing calcipotriol-assisted MAL-PDT with conventional MAL-PDT for the treatment of actinic keratosis: a randomized controlled trial.

To enhance the efficacy of photodynamic therapy (PDT) for actinic keratosis (AKs), physical and chemical pre-treatments, such as calcipotriol (CAL) have been suggested. To compare the long-term 12-month efficacy and safety between methylaminolevulinate (MAL)-PDT and prior application of topical CAL versus conventional MAL-PDT for AKs of the scalp. Twenty patients with multiple AKs on the scalp were randomized to receive conventional PDT on one side of the scalp and CAL-assisted PDT, in which CAL was applied daily for 15 days beforehand, on the other side. Patients were evaluated for AK clearance at three, six and 12 months thereafter. All 20 patients completed the study. At three months, overall AK clearance was 92.07% and 82.04% for CAL-PDT and conventional PDT, respectively (p < 0.001). Similar results were found at six and 12 months: 92.07% and 81.69% (p < 0.001), and 90.69% and 77.46% (p < 0.001) for CAL-PDT and conventional PDT, respectively. Grade I AKs showed a similar response rate for both sides (p = 0.055) at three months and significant differences were obtained at six (p = 0.001) and 12 months (p < 0.001) for CAL-PDT and conventional PDT. Grade II AKs showed greater improvement on the CAL-PDT side (89.55% vs 62.90%) (p < 0.001) at three months. No difference was found at six and 12 months. CAL-PDT proved to be safe and more effective than conventional PDT for the treatment of AKs on the scalp after 12 months. CAL pre-treatment may have enhanced the efficacy of PDT for AK treatment, however, larger trials are needed to corroborate our findings.

Dermatitis de contacto fotoalérgica y test de fotoparches: revisión de la literatura y aplicación de la técnica en clínica alemana de Santiago / Photoallergic contact dermatitis and test photopatches: literature review and application of the technique at clínica alemana de Santiago

Las fotodermatosis son un conjunto de patologías cutáneas originadas o agravadas por exposición a radiación ya sea solar o artificial. Se clasifican en cuatro categorías: 1. Idiopáticas o mediadas inmunológicamente 2. Dermatosis fotoagravadas, 3. Fotosensibilidad inducida por agentes y 4. Trastornos por reparación defectuosa del ADN. La fotosensibilidad inducida por agentes consiste en reacciones secundarias a la exposición de ciertos químicos, llamados fotosensibilizadores y a distintos tipos de radiación lumínica. Los fotosensibilizadores pueden ser de origen endógeno o exógeno, aquellos exógenos provienen desde el ambiente, fármacos u otros productos (tanto sistémicos como tópicos), los cuales sufren modificaciones estructurales al entrar en contacto con radiación, provocando como consecuencia, distintas manifestaciones cutáneas. En este artículo se revisarán principalmente las reacciones fototóxicas y fotoalérgicas (ambas, reacciones de fotosensibilidad inducidas por agentes exógenos) indagando en sus diferencias y el enfrentamiento clínico de cada una. También, se revisarán los exámenes que permiten estudiar los distintos diagnósticos diferenciales, especialmente el test de fotoparches, el cual está cobrando cada vez más importancia en la práctica clínica.

Photodermatoses are a group of skin diseases induced or aggravated by exposure to radiation, whether solar or artificial. They are classified into four general categories: 1. Idiopathic or immunologically mediated photodermatoses 2. Photoexacerbated dermatoses 3. Agent induced photosensitivity 4. DNA repair defects Photosensitivity induced by agents are secondary reactions to the exposure to some chemicals, called photosensitizers, and to different types of light radiation. Photosensitizers can be classified as exogenous or endogenous. Exogenous agents come from the environment, drugs or other products (both systemic and topical), which undergo structural changes when they come into contact with radiation, causing different skin manifestations as consequence. Differences between phototoxic and photoallergic reactions (both photosensitivity reactions induced by exogenous agents), the clinical approach of each one of them, and available tests that are used to make a diagnosis, especially, photo patch test will be reviewed in this article

Photodynamic therapy in superficial basal cell carcinoma treatment.

Basal cell cancer (BCC) is an epithelial neoplasm that arises from basal cells, which constitute the lower layer of the epidermis. Global statistics have shown the progressive increase in the incidence of skin cancer in several countries. The cumulative exposure to solar radiation (ultraviolet B) in the first two decades of life represents the critical risk for the disease. Preclinical and clinical trials have shown photodynamic therapy (PDT) as a promising innovation for treatment of skin cancers, especially to the non-melanoma group. The authors reviewed trials with photodynamic therapy in superficial basal cell carcinoma with different photosensitizers to better evaluate how PDT modifies the natural history of sBCC. We conclude trials should not assess only the immediate efficacy but the main goal of long-term effectiveness of the protocols in order to generate best evidence for clinical practice.

Photodynamic therapy for cutaneous hemangiosarcoma in dogs.

Cutaneous hemangiosarcoma is a malignant neoplasia that frequently occurs in dogs. The most effective treatment requires wide surgical excision of the tumor. To avoid mutilating surgeries, photodynamic therapy (PDT) could serve as an alternative treatment. This study aimed to treat cutaneous hemangiosarcomas in dogs using PDT with aluminium-chloride-phthalocyanine nanoemulsion (AlClPc-nano) as photosensitizer. Eight dogs with histopathological diagnosis of naturally occurring cutaneous hemangiosarcoma were treated. Animals were given intra and peritumoral injections of AlClPc-nano (13.3 µM). After 15 min, the masses were LED irradiated at a wavelength of 658-662 nm (80 mW potency) for 25 min (120 J/cm2 fluency). The number of sessions was based on lesion observations, with PDT sessions repeated every 7 days until the mass was no longer macroscopically visible. On that occasion, an excisional biopsy of the area was taken for histopathology analysis. Blood was collected from each animal before each PDT session and excisional biopsy for hematological analysis (blood counts; liver and kidney function). The number of PDT sessions varied from 2 to 4, depending on the size of the initial mass. Seven of the eight cases demonstrated complete remission of neoplasia. Microscopic analysis of the excisional biopsies showed necrosis and hemorrhage only, with no cancer cells, except in one case. During the treatment, inflammation and necrosis were macroscopically observed in the treated areas. The dogs did not show any alteration in blood parameters that could be related to the PDT. In conclusion, PDT with AlClPc-nano is a safe and effective treatment for cutaneous hemangiosarcoma in dogs.

Natural anthraquinones as novel photosentizers for antiparasitic photodynamic inactivation.

BACKGROUND: Cutaneous leishmaniasis (CL) is a vector-borne disease caused by obligate protist parasites from the genus Leishmania. The potential toxicity as well as the increased resistance of standard treatments has encouraged the development of new therapeutical strategies. Photodynamic inactivation (PDI) combines the use of a photosensitizer and light to generate reactive oxygen species and kill cells, including microorganisms. Vegetal kingdom constitutes an important source of bioactive compounds that deserve to be investigated in the search of naturally occurring drugs with leishmanicidal activity. PURPOSE: The purpose of this study was to test the antiparasitic activity of PDI (ApPDI) of five natural anthraquinones (AQs) obtained from Heterophyllaea lycioides (Rusby) Sandwith (Rubiacae). To support our results, effect of AQ mediated-PDI on parasite´s morphology and AQ uptake were studied. Cytotoxicity on fibroblasts was also evaluated. STUDY DESIGN/METHODS: Two monomers, soranjidiol (Sor) and 5-chlorosoranjidiol (5-ClSor) plus three bi-anthraquinones (bi-AQs), bisoranjidiol (Bisor), 7-chlorobisoranjidiol (7-ClBisor) and Lycionine (Lyc) were selected for this study. Recombinant L. amazonensis promastigote strain expressing luciferase was subjected to AQs and LED treatment. Following irradiation with variable light parameters, cell viability was quantified by bioluminescence. Alteration on parasite's morphology was analyzed by scanning electron microscopy (SEM). In addition, we verified the AQ uptake in Leishmania cells by fluorescence and their toxicity on fibroblasts by using MTT assay. RESULTS: Bisor, Sor and 5-ClSor exhibited photodynamic effect on L. amazonensis. SEM showed that promastigotes treated with Bisor-mediated PDI exhibited a significant alteration in shape and size. Sor and 5-ClSor presented higher uptake levels than bi-AQs (Bisor, Lyc and 7-ClBisor). Finally, Sor and Bisor presented the lowest toxic activity against fibroblasts. CONCLUSION: Taking together, our results indicate that Sor presents the highest specificity towards Leishmania cells with no toxicity on fibroblasts.

Photodynamic therapy with Bixa orellana extract and LED for the reduction of halitosis: study protocol for a randomized, microbiological and clinical trial.

BACKGROUND: Halitosis is an unpleasant breath odour that can interfere with the professional life, social life and quality of life of people who suffer from it. A modality of treatment that has been increasing in dentistry is antimicrobial photodynamic therapy (aPDT). Bixa orellana, popularly known as "urucum" is a plant native to Brazil. The seeds are used to produce a dye that is largely used in the food, textile, paint and cosmetic industries. The aim of this study is to verify whether aPDT with Bixa orellana extract and blue light-emitting diodes (LEDs) is effective in reducing halitosis. This method will also be compared with tongue scraping, the most commonly used conventional method for tongue coating removal, and the association of both methods will be evaluated. METHODS/DESIGN: A randomized clinical trial will be conducted at the dental clinic of the Universidade Nove de Julho. Thirty-nine patients will be divided by block randomization into three groups (n = 13) according to the treatment to be performed. In Group 1, tongue scraping will be performed by the same operator in all patients for analysis of the immediate results. Patients will also be instructed on how to use the scraper at home. Group 2 will be treated with aPDT with Bixa orellana extract and the LED light curing device: Valo Cordless Ultradent®. Six points in the tongue dorsum with a distance of 1 cm between them will be irradiated. The apparatus will be pre-calibrated at wavelength 395-480 nm for 20 s and 9.6 J per point. In Group 3, patients will be submitted to the tongue scraping procedure, as well as to the previously explained aPDT. Oral air collection with the Oral Chroma™ and microbiological collections of the tongue coating shall be done before, immediately after and 7 days after treatment for comparison. DISCUSSION: Halitosis treatment is a topic that still needs attention. The results of this trial could support decision-making by clinicians regarding aPDT using blue LEDs for treating halitosis on a daily basis, as most dentists already have this light source in their offices. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03346460 . Registered on 17 November 2017.

Effectiveness and safety of 0·5% colchicine cream vs. photodynamic therapy with methyl aminolaevulinate in the treatment of actinic keratosis and skin field cancerization of the forearms: a randomized controlled trial.

BACKGROUND: Skin field cancerization (SFC) is a process that occurs in areas of the skin that have undergone genomic alterations induced by ultraviolet radiation. Actinic keratosis (AK) is a sign of its activity. OBJECTIVES: To evaluate the effectiveness and safety of 0·5% colchicine (COL) cream vs. methyl aminolaevulinate photodynamic therapy (MAL-PDT) in the treatment of AK and SFC. METHODS: We conducted a randomized, open, intrasubject controlled trial. A total of 36 participants with 3-10 AKs on each forearm were treated with either COL cream (twice daily for 10 days) or a single session of MAL-PDT and were reassessed after 60 days. The clinical evaluation was performed using AK count, forearm photoageing scale (PAS) and AK degree (AKD). Patients underwent central forearm biopsies and histopathological evaluation by keratinocyte intraepithelial neoplasia (KIN) assessment, epithelial atrophy and immunohistochemistry (p53/Ki67). RESULTS: Overall, 50% of patients were male. The mean age was 70·9 years (SD 8·6) and phototypes I and II were predominant (89%). Total clearance was observed in six (17%) forearms treated with COL and seven (19%) forearms treated with MAL-PDT (P = 0·76); partial clearance was observed in 44% of forearms in the COL group and 67% of forearms in the MAL-PDT group (P = 0·07). In both COL and MAL-PDT groups, reductions in PAS (-6% vs. -6%) and AKD (-45% vs. -40%) were observed. KIN normalized in 28% of patients treated with MAL-PDT and 20% of those treated with COL. Epithelial atrophy reduced after treatment (P < 0·01). Expression levels of Ki67 and p53 were also assessed. Mild or moderate adverse effects were similar for both groups. CONCLUSIONS: COL 0·5% cream and MAL-PDT are safe and effective for treating SFC.

Surtos de fotossensibilização e dermatite alérgica em ruminantes e equídeos no Nordeste do Brasil / Outbreaks of photosensitization and allergic dermatitis in ruminants and equidae in northeastern Brazil

O presente estudo foi conduzido com o objetivo de determinar as causas de fotossensibilização em ruminantes e equídeos no Nordeste do Brasil, através da revisão dos laudos de exames arquivados no Laboratório de Patologia Veterinária da Universidade Federal da Paraíba. Durante os quatro anos do estudo foram diagnosticados 22 surtos de fotossensibilização, incluindo 11 surtos de fotossensibilização primária e oito surtos de fotossensibilização hepatógena. A intoxicação por Froelichia humboldtiana foi a principal causa de fotossensibilização e a única causa de fotossensibilização primária. As espécies mais gravemente afetadas por fotossensibilização primária foram os asininos, caprinos, bovinos e ovinos, mas os equinos e mulas também são afetados. A intoxicação por Brachiaria decumbens foi a principal causa de fotossensibilização hepatógena e afetou apenas os ovinos e bovinos. Outras plantas associadas com fotossensibilização hepatógena incluíram Enterolobium contortisiliquum e Lantana camara. Dermatite alérgica foi diagnosticada em dois rebanhos ovinos e em um cavalo. Os animais tinham lesões crônicas, caracterizadas por alopecia, crostas e hiperpigmentação no topo da cabeça, ao redor dos olhos (ovinos) e nos membros (equino). O prurido foi o principal sinal clínico observado nos casos de fotossensibilização primária e hipersensibilidade à picada de insetos.(AU)

The study was conducted to determine the causes of photosensitization in ruminants and equidae in northeastern Brazil through a review of the files at the Laboratório de Patologia Veterinária of Universidade Federal da Paraíba. During four years of the study 22 outbreaks of photosensitization were diagnosed, including 11 outbreaks of primary photosensitization and eight outbreaks of hepatogenous photosensitization. Poisoning by Froelichia humboldtiana was the main cause of photosensitization, and the only cause of primary photosensitization. The most severely affected animals by primary photosensitization are donkeys, goats, cattle and sheep, but horses and mules may also be affected. Poisoning by Brachiaria decumbens was the main cause of hepatogenous photosensitization, and affected only sheep and cattle. Other plants associated with hepatogenous photosensitization in cattle include Enterolobium contortisiliquum and Lantana camara. Allergic dermatitis was diagnosed in two flocks of sheep and in a horse. The animals had chronic lesions characterized by areas of alopecia, crusts and hyperpigmentation on the head, around the eyes (sheep) and at the legs (horse). Itching was the main clinical sign in cases of primary photosensitization and insect hypersensitivity.(AU)

Surtos de fotossensibilização e dermatite alérgica em ruminantes e equídeos no Nordeste do Brasil / Outbreaks of photosensitization and allergic dermatitis in ruminants and equidae in northeastern Brazil

O presente estudo foi conduzido com o objetivo de determinar as causas de fotossensibilização em ruminantes e equídeos no Nordeste do Brasil, através da revisão dos laudos de exames arquivados no Laboratório de Patologia Veterinária da Universidade Federal da Paraíba. Durante os quatro anos do estudo foram diagnosticados 22 surtos de fotossensibilização, incluindo 11 surtos de fotossensibilização primária e oito surtos de fotossensibilização hepatógena. A intoxicação por Froelichia humboldtiana foi a principal causa de fotossensibilização e a única causa de fotossensibilização primária. As espécies mais gravemente afetadas por fotossensibilização primária foram os asininos, caprinos, bovinos e ovinos, mas os equinos e mulas também são afetados. A intoxicação por Brachiaria decumbens foi a principal causa de fotossensibilização hepatógena e afetou apenas os ovinos e bovinos. Outras plantas associadas com fotossensibilização hepatógena incluíram Enterolobium contortisiliquum e Lantana camara. Dermatite alérgica foi diagnosticada em dois rebanhos ovinos e em um cavalo. Os animais tinham lesões crônicas, caracterizadas por alopecia, crostas e hiperpigmentação no topo da cabeça, ao redor dos olhos (ovinos) e nos membros (equino). O prurido foi o principal sinal clínico observado nos casos de fotossensibilização primária e hipersensibilidade à picada de insetos.(AU)

The study was conducted to determine the causes of photosensitization in ruminants and equidae in northeastern Brazil through a review of the files at the Laboratório de Patologia Veterinária of Universidade Federal da Paraíba. During four years of the study 22 outbreaks of photosensitization were diagnosed, including 11 outbreaks of primary photosensitization and eight outbreaks of hepatogenous photosensitization. Poisoning by Froelichia humboldtiana was the main cause of photosensitization, and the only cause of primary photosensitization. The most severely affected animals by primary photosensitization are donkeys, goats, cattle and sheep, but horses and mules may also be affected. Poisoning by Brachiaria decumbens was the main cause of hepatogenous photosensitization, and affected only sheep and cattle. Other plants associated with hepatogenous photosensitization in cattle include Enterolobium contortisiliquum and Lantana camara. Allergic dermatitis was diagnosed in two flocks of sheep and in a horse. The animals had chronic lesions characterized by areas of alopecia, crusts and hyperpigmentation on the head, around the eyes (sheep) and at the legs (horse). Itching was the main clinical sign in cases of primary photosensitization and insect hypersensitivity.(AU)

Photodynamic inactivation of Candida ssp. on denture stomatitis. A clinical trial involving palatal mucosa and prosthesis disinfection.

Denture stomatitis (DS) is the most common oral fungal infection in denture wearers. Photodynamic inactivation (PDI) has been showing to be an effective technique in vivo against fungi, including fungal infections in the oral cavity. The disinfection of both oral mucosa and denture may represent a real advantage in terms of fungus control. This clinical study was designed to explore methylene blue (MB)-mediated PDI on oral mucosa and prosthesis of patients with DS. Subjects with DS were divided into two groups. One group received treatment based on the use of oral miconazole gel 2% (MIC). The other group received treatment by PDI using MB at 450 µg/mL and a diode laser (λ = 660 nm) with 100 mW and fluence of 28 J/cm2. Clinical outcome was evaluated regarding the degree of oral mucosa erythema and microbiological reduction of Candida spp. located in both palatal mucosa and prosthesis. Our results showed that PDI was significantly more effective than MIC in ameliorating inflammation after 15 days. Following 30 days, no statistically significant differences were observed between groups. Regarding the fungal burden, although the MIC group has presented more pronounced inactivation than PDI for both mucosa and prosthesis, no statistically significant differences were detected between them. This clinical study suggests that PDI can reduce fungal load and decrease the inflammation degree in patients with Candida-associated denture stomatitis.

A randomized split-scalp study comparing calcipotriol-assisted methyl aminolaevulinate photodynamic therapy (MAL-PDT) with conventional MAL-PDT for the treatment of actinic keratosis.

BACKGROUND: Topical photodynamic therapy (PDT) is an approved treatment for actinic keratosis (AK). To enhance the efficacy of PDT for AKs, physical and chemical pretreatments have been suggested. OBJECTIVES: To compare the efficacy and safety of the combination of topical calcipotriol (CAL) before methyl aminolaevulinate (MAL)-PDT for AKs of the scalp vs. conventional MAL-PDT in a randomized controlled clinical trial. METHODS: Twenty patients with multiple AKs on the scalp were randomized to receive conventional MAL-PDT with previous curettage on one side of the scalp and CAL-assisted MAL-PDT once a day for 15 days before illumination on the other side. After 3 months, patients were evaluated for clearance of AKs, side-effects and histopathology before and after the procedure. Protoporphyrin IX (PpIX) fluorescence was measured before and after illumination on both sides. RESULTS: All 20 patients completed the study. Overall AK clearance rates were 92·1% and 82·0% for CAL-PDT and conventional PDT, respectively (P < 0·001). Grade 1 AKs showed similar response rates for both sides (P = 0·055). However, grade II AKs showed more improvement on the CAL-PDT side (90%) than on the MAL-PDT side (63%) (P < 0·001). Before illumination, PpIX fluorescence intensity was higher on the CAL-assisted side (P = 0·048). The treatment was more painful on the CAL-PDT side, although well tolerated. The mean visual analogue scale score was 5·4 ± 1·4 on the CAL-PDT side and 4·0 ± 0·69 on the conventional MAL-PDT side (P = 0·001). Side-effects such as erythema (P = 0·019), oedema (P = 0·002) and crusts (P < 0·001) were more pronounced on the CAL-assisted side. Histopathological analyses were obtained from five patients and both sides showed improved keratinocyte atypia following PDT, with slightly more improvement on the CAL-assisted side. CONCLUSIONS: CAL-assisted PDT proved to be safe and more effective than conventional MAL-PDT for the treatment of AKs on the scalp. CAL pretreatment increased PpIX accumulation within the skin and may have enhanced the efficacy in this first human trial.

A new optical intra-tissue fiber irradiation ALA-PDT in the treatment of acne vulgaris in rabbit model: improved safety and tolerability.

BACKGROUND: Photodynamic therapy with topical aminolevulinic acid (ALA-PDT) has been suggested to be effective in treatment of acne vulgaris. However, adverse events occur during and after treatment. OBJECTIVES: To compare the efficacy and tolerability of optical intra-tissue fiber irradiation (OFI) ALA-PDT versus traditional ALA-PDT in treatment of acne vulgaris in rabbit models. METHODS: Twenty-five rabbits of clean grade were used. Twenty rabbits were randomly selected to establish acne model and the other five were used as control. Rabbits in model group (40 ears) were further divided into four groups (10 ears/group): I, OFI-ALA-PDT with the head of optical fiber inserted into the target lesion (intra-tissue); II, traditional ALA-PDT group; III, OFI group; IV, blank control group without any treatment. Uncomfortable symptoms, adverse events, and effectiveness rates were recorded on post-treatment day 14, 30, and 45. RESULTS: On post-treatment day 14, the effectiveness rate in OFI-ALA-PDT group was obviously higher than that of the other three groups (P<0.05). However, no improved effects were observed in OFI-ALA-PDT group on day 30 and 45. During the period of treatment, the frequencies of uncomfortable symptoms in ALA-PDT group were obviously higher than those in the other three groups (P<0.05). The adverse event rate in OFI-ALA-PDT group was obviously lower than that of the ALA-PDT group (P<0.05). STUDY LIMITATIONS: The unblindness of the study and temporary animal models of acne induced may hamper the assessment and monitoring of the results, and future studies are still needed to clarify it further. CONCLUSION: The OFI-ALA-PDT group (intra-tissue irradiation) showed no improved efficacy on treating rabbit ear acne but had higher safety and better tolerability.

Assessing daylight & low-dose rate photodynamic therapy efficacy, using biomarkers of photophysical, biochemical and biological damage metrics in situ.

BACKGROUND: Sunlight can activate photodynamic therapy (PDT), and this is a proven strategy to reduce pain caused byconventional PDT treatment, but assessment of this and other alternative low dose rate light sources, and their efficacy, has not been studied in an objective, controlled pre-clinical setting. This study used three objective assays to assess the efficacy of different PDT treatment regimens, using PpIX fluorescence as a photophysical measure, STAT3 cross-linking as a photochemical measure, and keratinocyte damage as a photobiological measure. METHODS: Nude mouse skin was used along with in vivo measures of photosensitizer fluorescence, keratinocyte nucleus damage from pathology, and STAT3 cross-linking from Western blot analysis. Light sources compared included a low fluence rate red LED panel, compact fluorescent bulbs, halogen bulbs and direct sunlight, as compared to traditional PDT delivery with conventional and fractionated high fluence rate red LED light delivery. RESULTS: Of the three biomarkers, two had strong correlation to the PpIX-weighted light dose, which is calculated as the product of the treatment light dose (J/cm2) and the normalized PpIX absorption spectra. Comparison of STAT3 cross-linking to PpIX-weighted light dose had an R=0.74, and comparison of keratinocyte nuclear damage R=0.70. There was little correlation to PpIX fluorescence. These assays indicate most of the low fluence rate treatment modalities were as effective as conventional PDT, while fractionated PDT showed the most damage. CONCLUSIONS: Daylight or artificial light PDT provides an alternative schedule for delivery of drug-light treatment, and this pre-clinical assay demonstrated that in vivo assays of damage could be used to objectively predict a clinical outcome in this altered delivery process.

Oral hygiene in intensive care unit patients with photodynamic therapy: study protocol for randomised controlled trial.

BACKGROUND: In intensive care units (ICUs), nosocomial infections are prevalent conditions and they have been related to high mortality indexes. Some studies have suggested that inefficient oral hygiene and ventilator-associated pneumonia (VAP) are related. Nowadays, in the Brazilian public health system there is no well-defined protocol for oral hygiene in an ICU. Due to the drawbacks of the use of antibiotics, photodynamic therapy (PDT) has emerged as an interesting technique in order to reduce antimicrobial-resistant pathogens. Methylene blue (MB) is the most common chemical agent for PDT in Brazil. However, new formulations for improved effectiveness are still lacking. The objective of this study is to evaluate the use of an MB mouthwash as an effective oral-hygiene procedure in an ICU and to show that oral hygiene using PDT with MB mouthwash may reduce VAP frequency to rates similar to, or higher than, chlorhexidine. METHODS: Phase 1 will evaluate the most effective cleaning procedure, while phase 2 will correlate oral hygiene to VAP incidence. At the start of phase 1, the ICU patients will be randomly allocated into three different groups (10 patients/group): the efficacy of chlorhexidine, classical MB-PDT, and mouthwash MB-PDT will all be measured for the quantification of viable bacteria, both pre- and post-treatment, by a Reverse Transcription Polymerase Chain Reaction (RT-PCR). In phase 2, the most effective procedure found in phase 1 and a mechanical cleaning with filtered water will be carried out daily, once a day, over 5 days, with a total of 52 ICU patients randomly allocated into the two groups. The clinical records will be evaluated in order to find any pneumonic diagnoses. DISCUSSION: Since a variety of bacterial species are related to VAP, a universal primer for bacteria will be used in order to quantify the total bacteria count in the participants' samples. In order to quantify only the living bacteria before DNA extraction, the samples will be treated with propidium monoazide. This will infiltrate the dead bacteria and will intercalate the DNA bases, avoiding their DNA amplification. This will be the first trial to evaluate MB-PDT in a mouthwash formula that can increase the effectiveness due to the control of MB aggregation. The results of this study will be able to generate an easy and low-cost protocol to be used in an ICU for the Brazilian public health system. TRIAL REGISTRATION: This protocol was approved by the Research Ethics Committee of the Conjunto Hospitalar do Mandaqui (1.317.834, CAAE: 49273515.9.3001.5551) and it was registered in Registro Brasileiro de Ensaios Clínicos (ReBEC number: RBR-94bvrc;). First received: 12 July 2015; 1st version 6 June 2016. Data will be published in a peer-reviewed journal.

Photodynamic Therapy treatment of onychomycosis with Aluminium-Phthalocyanine Chloride nanoemulsions: A proof of concept clinical trial.

The conventional treatment of onychomycosis, a common fungal infection, consists in the use of local and systemic drugs for 4-6 months. This long protocol is often ineffective due to patient compliance, and usually promotes important collateral effects such as liver and kidney failure. As the alternative, Photodynamic Therapy (PDT) has been used as a noninvasive alternative local treatment for onychomycosis due to the reduction of systemic side effects, fact indicates their use for patients undergoing other systemic treatments. In the present article, we evaluated the effectiveness, as well as the safety of PDT mediated by Aluminium-Phthalocyanine Chloride, entrapped in nanoemulsions, as a drug carrier, to treat onychomycosis in a proof of concept clinical trial. To the date, this is the first published clinical trial that uses PDT mediated by nanomedicines to treat onychomycosis. As main results, we can highlight the safety of the clinical protocol and the antifungal effectiveness similar to the conventional treatments. We observed the (1) clinical cure of 60% of treated lesions; (2) the absence of local and systemic adverse effects; (3) from these clinically healed lesions, 40% were negative for fungal infection in laboratorial exams; and (4) nails that presented negative fungal culture were kept without fungal infection for at least four weeks. The innovation of this approach is the absence of collateral effects, due to the local therapeutically treatment, and the possibility to repeat the treatment without inducing fungal resistance, a fact that indicates this approach as a possible alternative protocol for onychomycosis management.

A new optical intra-tissue fiber irradiation ALA-PDT in the treatment of acne vulgaris in rabbit model: improved safety and tolerability

Abstract Background: Photodynamic therapy with topical aminolevulinic acid (ALA-PDT) has been suggested to be effective in treatment of acne vulgaris. However, adverse events occur during and after treatment. Objectives: To compare the efficacy and tolerability of optical intra-tissue fiber irradiation (OFI) ALA-PDT versus traditional ALA-PDT in treatment of acne vulgaris in rabbit models. Methods: Twenty-five rabbits of clean grade were used. Twenty rabbits were randomly selected to establish acne model and the other five were used as control. Rabbits in model group (40 ears) were further divided into four groups (10 ears/group): I, OFI-ALA-PDT with the head of optical fiber inserted into the target lesion (intra-tissue); II, traditional ALA-PDT group; III, OFI group; IV, blank control group without any treatment. Uncomfortable symptoms, adverse events, and effectiveness rates were recorded on post-treatment day 14, 30, and 45. Results: On post-treatment day 14, the effectiveness rate in OFI-ALA-PDT group was obviously higher than that of the other three groups (P<0.05). However, no improved effects were observed in OFI-ALA-PDT group on day 30 and 45. During the period of treatment, the frequencies of uncomfortable symptoms in ALA-PDT group were obviously higher than those in the other three groups (P<0.05). The adverse event rate in OFI-ALA-PDT group was obviously lower than that of the ALA-PDT group (P<0.05) Study limitations: The unblindness of the study and temporary animal models of acne induced may hamper the assessment and monitoring of the results, and future studies are still needed to clarify it further. Conclusion: The OFI-ALA-PDT group (intra-tissue irradiation) showed no improved efficacy on treating rabbit ear acne but had higher safety and better tolerability.

PDT and emerging therapies for Actinic Keratosis-A resource letter.

Aktinic Keratosis is common and if left untreated may develop into life threatening squamous cell carcinoma. Therefore early intervention is the standard of care. While many treatments are available PDT continues to move to the for - front for this indication (Brito et al., 2016 [31]). Topical PS is commercially available that are able to reliably ablate these lesions. Innovative protocols including sunlight, large volume LED arrays and maneuvers to improve treatment parameters and cosmesis continue to make this a worldwide treatment of choice for AK.

Evaluation of the effectiveness of photodynamic therapy for the endodontic treatment of primary teeth: study protocol for a randomized controlled clinical trial.

BACKGROUND: The elimination of pathogenic microorganisms from the root canal system is one of the major steps required for successful endodontic treatment. The aim of the proposed study is to conduct a randomized, controlled, clinical trial for the clinical and radiographic evaluation of the effectiveness of photodynamic therapy during the endodontic treatment of primary teeth. METHODS: Thirty primary anterior teeth in children aged 3 to 6 years old will be randomly divided into 2 groups: a control group, which will receive conventional treatment, and an experimental group, which will be subjected to photodynamic therapy. Microbiological evaluations will be performed before and after endodontic treatment. Moreover, clinical and radiographic evaluations will be performed on the day of treatment as well as 1, 3 and 6 months after treatment. Comparisons will be made of the two study groups. The data will be tabulated and presented in a descriptive, analytical fashion. Depending on the distribution (normal or non-normal), either the t test, ANOVA or the Mann-Whitney test will be used for analysis of the variables. The Wilcoxon test will be used for comparisons before and after treatment. P values<0.05 (95% significance level) will be considered indicative of statistically significant differences. DISCUSSION: As successful endodontic treatment is directly related to intra-canal bacterial disinfection and considering the difficult task of endodontic treatment in primary teeth, often due to difficulties in controlling young children, the internal anatomy of root canals and root resorption, the alternative of using PDT is a painless,easy-to-administer method that does not lead to microbial resistance and can assist in the achievement of successful endodontic treatment in primary teeth by eliminating the pain children can experience due to retreatment as well as premature tooth loss. TRIAL REGISTRATION: The protocol for this study was registered with Clinical Trials number NCT02485210 on 30 july 2015.