Anti-tumor effect of PDT using Photofrin in a mouse angiosarcoma model

Angiosarcoma, a malignant tumor of vascular endothelial cell origin, is a lethal disease for which complete cure is rarely seen. The objective of this study was to determine the efficiency of photodynamic therapy (PDT) as a new treatment for angiosarcoma. PDT (630 nm, 25 J/cm²) using Photofrin for a mouse angiosarcoma cell line of human origin (ISOS-1) showed that the rate of cell death increased with increase in the concentration of a photosensitizer (LD₅₀: ∼2 μg/ml). Furthermore, PDT (630 nm, 100 J/cm²) with Photofrin (5 mg/kg, i.v.) in mice transplanted with ISOS-1 cells resulted in complete disappearance of the tumor in 40% of mice and marked inhibition of tumor growth in the remaining 60%. Significant increases in TUNEL-positive cells and Ki-67-positive cells ware seen 4 h after PDT, indicating that PDT led to not only cell death but also inhibition of the proliferation of angiosarcoma cells. The results show that PDT is effective for treatment of angiosarcoma.     

Fluorescence digital photography of acne using a light-emitting diode illuminator

BACKGROUND/PURPOSE: The fluorescence findings of several dermatological diseases, such as erythrasma, tinea versicolor, and acne are helpful for diagnosis and follow-up. However, many experience difficulty taking photographic images of fluorescence. The aim of this study was to develop a 405 nm light-emitting diode (LED) system for fluorescence digital photography of acne and to determine whether such a diode can be used to evaluate acne. METHODS: Eight healthy acne patients were compared with controls by fluorescence digital photography using a digital camera equipped with a 405 nm LED illuminator. Digital photographs were taken by two different ways of exposure, i.e. appropriate exposure level and longer exposure. One side of the nose, cheek, and glabella was compared. The numbers and extents of fluorescence dots were counted and measured. As normal controls, seven individuals with apparent oiliness and no acne were enrolled. RESULTS: Red fluorescent facial dots were observed and photographed digitally using the 405 nm LED illuminator. These were more numerous and extensive on the glabella and cheeks of acne patients. CONCLUSION: Fluorescence digital photography of acne was successfully performed using a 405 nm LED illuminator. This illuminator could be used for acne evaluations.     

Photodynamic therapy using light-emitting diodes for the treatment of viral warts

Photodynamic therapy with topical 5-aminolevulinic acid is an effective and safe treatment for actinic keratosis and superficial non-melanoma skin cancer. Further, some studies have reported good efficacy when using photodynamic therapy to treat viral warts. The light-emitting diode is an incoherent, narrow-spectrum light source. The purpose of this study is to evaluate the efficacy of photodynamic therapy using a light-emitting diode for viral warts. Six patients with a total of 41 foot and hand warts were recruited in this study. They were treated with 20% 5-aminolevulinic acid cream under occlusion for 5 h. Thereafter, the treated area was irradiated with the light from a red light-emitting diode (633 ± 6 nm) with a dose of 126 J/cm². This treatment was repeated at 2- or 3-week intervals. The rate of improvement observed in patients was 68.3%. The adverse effects included mild to moderate pain and erythema, which was well-tolerated by all six patients. No patients withdrew from the study due to the adverse effects. Photodynamic therapy with topical 5-aminolevulinic acid using the light from a red light-emitting diode has the advantage of non-invasiveness, minimal associated adverse reactions, and production of good results in a significant proportion of cases: therefore, it is an alternative treatment for recalcitrant viral warts.     

A short-term screening protocol, using fibrillin-1 as a reporter molecule, for photoaging repair agents

Photoaged skin is characterized by coarse and fine wrinkles. The mechanisms of wrinkle formation are undetermined, but appear to be due to changes within the matrix of the dermis and at the dermal-epidermal junction. Previous studies have identified marked reductions in procollagens I and III, collagen VII, and the fibrillin-rich microfibrillar apparatus in this area. Topically applied all-trans retinoic acid can repair photoaged dermal matrix, but this takes at least 6 mo of treatment. In this study, we have examined the abundance and distribution of fibrillin-1 prior to, and following, 192 wk of all-trans retinoic acid treatment. We have further developed a short-term protocol to determine the utility of potential repair agents, using fibrillin-1 as the marker for outcome. Individuals with clinically assessed severe photoaging were recruited to the study (n = 8). 0.025% all-trans retinoic acid, 5% sodium lauryl sulfate (irritant control), or vehicle were applied under occlusion to photoaged extensor forearm. A fourth control area was also occluded. After 96 h, punch biopsies were taken under local anesthesia and processed for either transmission electron microscopy or snap frozen. Frozen sections were prepared for immunohistochemistry and in situ hybridization immunohistochemistry. Electron microscopy revealed aberrant elastic fibers in the papillary dermis of photoaged forearm skin, with sparse microfibrillar apparatus and interstitial collagen. After application of 0.025% all-trans retinoic acid, there was increased deposition of both these dermal matrix components, with the aberrant elastic fibers no longer apparent. Significant increases (p < 0.05) were observed at the protein and mRNA levels for fibrillin-1 following all-trans retinoic acid and sodium lauryl sulfate treatments, with all-trans retinoic acid having a significantly greater effect than irritant control (p < 0.001); however, neither application had significant effect on the abundance of collagen VII or its mRNA. Investigation of collagen I synthesis revealed no difference following treatments. To ascertain the clinical relevance of using fibrillin-1 as a marker for photoaging, facial skin was biopsied at baseline and after long-term (192 wk) topical all-trans retinoic acid treatment (n = 5). Biopsies were wax-embedded and sections prepared for immunohistochemistry for fibrillin-1. Significant increases in the abundance of the microfibrillar apparatus was observed proximal to the dermal- epidermal junction (p < 0.001) following long-term all-trans retinoic acid application. This study indicates that all-trans retinoic acid can significantly affect fibrillin-1 content in photoaged skin. Furthermore, fibrillin-1 can be used as a "reporter" molecule in short-term protocols for testing the utility of topical agents in the repair of photoaged skin.     

Biological effects of a new ultraviolet A1 prototype based on light-emitting diodes on the treatment of localized scleroderma

Ultraviolet A₁ (UVA₁) phototherapy (spectral range 340-400 nm) is a well-established treatment option for various skin diseases such as localized scleroderma. Recent improvements of conventional UVA₁ light sources (metal-halide or fluorescent lamps) have brought attention to a new light-emitting diode (LED) technology with remarkable advantages in handling and clinical routine. This study provides a preclinical histological and molecular evaluation of an LED-based UVA₁ prototype with a narrower spectral range (360-400 nm) for treating localized scleroderma. Scleroderma mouse models and fibroblasts in vitro were exposed to LED-based UVA₁ phototherapy or to irradiation with a commercially available metal-halide lamp emitting low-dose (20, 40 J/cm²), medium-dose (60 J/cm²) and high-dose (80, 100 J/cm²) UVA₁ light. Both UVA₁ light sources affected inflammatory genes (IL-1α and IL-6) and growth factors (TGFß-1 and TGFß-2). Increased collagen type 1 was reduced after UVA₁ phototherapy. Matrix metalloproteinase-1 was more enhanced after a medium dose of LED-based UVA₁ phototherapy than after conventional treatment. In vivo, dermal thickness and the amount of collagen were reduced after both treatment methods. Remarkably, myofibroblasts were more effectively reduced by a medium dose of LED-based UVA₁ phototherapy. The study indicates that LED-based UVA₁ phototherapy yields similar or even better results than conventional treatment. In terms of biosafety and patient comfort, LED-based UVA₁ phototherapy offers clear advantages over conventional treatment because of the use of a narrower and less harmful UVA₁ spectrum, less heat generation and shorter treatment times at the same irradiation intensity. Clinical studies are required to confirm these results in patients with localized scleroderma.     

Complete resolution of a squamous cell carcinoma of the skin using intralesional 5-aminolevulinic acid photodynamic therapy intralesional PDT for SCC

We present an 82-year-old female patient with a 2-year history of an infiltrative squamous cell carcinoma (SCC) on her right cheek. The patient was treated with one intralesional photodynamic therapy (PDT) session using 10% 5-aminolevulinic acid solution. We used red light by a non-coherent light source at a light dose of 100 J/cm2 and a fluency rate of 100 mW/cm2. Complete clinical and histological response was achieved 3 months after the treatment procedure. Cosmetic outcome was evaluated as fair. The patient remains disease free with the absence of any clinical sign of recurrence 16 months after PDT. Long-term follow-up is needed for assessment of recurrences. Optimization of the therapeutic protocol, as well as justification of our results in larger studies are needed in order to elicit safe conclusions.     

Full-face laser resurfacing using a supplemented topical anesthesia protocol

BACKGROUND: Laser resurfacing has become a popular modality for the treatment of photodamaged skin, rhytids, and acne scarring. In many cases, this procedure is performed under general anesthesia or intravenous sedation in conjunction with nerve blocks and local infiltration. OBJECTIVE: To evaluate the safety and efficacy of facial carbon dioxide laser resurfacing using a supplemented topical anesthesia protocol. DESIGN: Nonrandomized case series of patients observed for 1 year. SETTING: Outpatient surgery center. PATIENTS: Two hundred consecutive patients undergoing treatment for facial rhytids or acne scarring.Intervention Full-face carbon dioxide laser resurfacing procedures were performed using a supplemented topical anesthesia protocol. Pretreatment medications included diazepam, oral analgesics, and intramuscular ketorolac tromethamine. MAIN OUTCOME MEASURES: Tolerability of procedure, healing times, and adverse effects. RESULTS: Topical anesthesia provided effective and sufficient anesthesia in most cases. Only 10 of 200 patients required additional anesthesia (regional nerve blocks and/or local infiltration). Substantial improvement of rhytids, photodamage, and acne scarring was observed. Posttreatment hypopigmentation was seen in 1 patient. Scarring was not observed.Conclusion A supplemented topical anesthesia protocol for full-face laser resurfacing is a safe and effective alternative to traditional anesthesia strategies.     

Digital camera images obtained using a light-emitting diode illuminator and their dermatological applications

BACKGROUND/PURPOSE: Although digital cameras have powerful macrocapabilities, flash macrophotographs are often unsatisfactory. The aim of this study was to develop a light-emitting diode (LED) illuminator for macro digital photography that allows colorimetric investigations of the skin. METHODS: We devised an LED illuminator suitable for acquiring super-macro digital images of the skin. Reference CIELAB color chart values were compared statistically with computed values from digital images in order to obtain equations for real CIELAB values. Using these, we acquired and analyzed images of various dermatological conditions using an LED illuminator. RESULTS: The images obtained with the devised LED illuminator were more reproducible than flash-assisted photographs. With proper camera settings, the devised LED illuminator and the color analysis method developed during this study provided digital skin images containing colorimetric information. CONCLUSION: A digital camera equipped with an LED illuminator is a useful tool for dermatological research and clinical practice.     

A standard protocol for phototoxicity testing

Based on experience accumulated in a number of laboratories, a standardized protocol for phototoxicity testing in experimental animals by the dermal route is presented. By conducting a limited interlaboratory study, demonstrating a high degree of consistency using 8-methoxypsoralen {8-MOP) and acridine, the sensitivity and reproducibility of the proposed methodology is demonstrated. Important aspects of performing phototoxicity testing are discussed.     

Dual wavelength 5-aminolevulinic acid photodynamic therapy using a novel flexible light-emitting diode unit

Background

Photosensitizers used for photodynamic therapy (PDT) to treat dermatologic disease are metabolized into mainly protoporphyrin IX (PpIX), which has five absorption wavelength peaks: 410?nm, 510?nm, 545?nm, 580?nm, and 630?nm. Although only red light around 635?nm and blue light around 400?nm are used as light sources for PDT, the efficiency of PDT might be improved by using multiple wavelengths, including those that correspond to the other absorption peaks of PpIX. Furthermore, because the target disease often occurs on the face, a flexible-type light-source unit that can be fitted to the lesion without unnecessarily exposing the mucous membranes, e.g., the eyes, nostrils, and mouth, is preferred.

The benefits of implementing a new skin care protocol in nursing homes

This study explored the extent to which a new skin care protocol comprising a skin cleanser, barrier cream and barrier film could be implemented in nursing homes, and its effects on patients' skin condition, staff time and associated costs. A pre- and post-intervention study design was used. Data were collected on current skin condition and skin care procedures, before and after the introduction of a new skin care protocol. Nurses and carers were observed as they undertook skin care following episodes of incontinence. The time taken, products and amounts used were recorded. The presence and severity of incontinence dermatitis was recorded, together with the presence and severity of pressure ulceration. A supportive education programme was delivered to staff. All patients with incontinence and all staff working in six nursing homes were included in this study. Two nursing homes were randomly selected to participate in detailed skin assessments, documentation of skin care procedures and product usage. A total of 164 patients were included in detailed assessments, 79 pre-intervention, 85 post-intervention; 49 were male (29.9%) and 115 were female (70.1%). Their mean age was 83.44 years (standard deviation = 8.38). Only 3% of patients were under 70 years of age, with 72% over 80 years of age. Pre-intervention 29.1% were incontinent of urine only, 64.6% were doubly incontinent and 6.3% were catheterised. Post-intervention 29.4% had urinary incontinence, 65.9% were doubly incontinent, and 4.7% were catheterised. Skin condition was maintained or improved using the new skin care protocol. The presence of grade 1 pressure ulcers was found to significantly decrease over time (p = 0.042). The presence of incontinence dermatitis was found to be significantly lower after introducing the skin care protocol (p = 0.021). There was significant reduction in time taken to deliver skin care post-intervention (p < 0.001) with a mean time saving of 4 minutes and 2 seconds, per patient per procedure. On average this procedure was carried out 8.5 times per day, giving a time saving of 34 minutes and 17 seconds per patient per day using the new skin care protocol. This was associated with an average saving per patient per day of 8.83 Pounds for qualified staff and 3.43 Pounds for unqualified staff. Staff adherence to the new skin care protocol was good, with only one observed episode when the protocol was not followed, suggesting a high degree of success in its implementation. This study demonstrated that the introduction of a new skin care protocol, supported by an educational programme, maintained or improved patients' skin condition, and significantly reduced the resources used in delivering nursing care.     

Split-face-study using two different light sources for topical PDT of actinic keratoses:non-inferiority of the LED system

Background: Photodynamic therapy (PDT) with 5-amino-4-oxo-pentanoate (methylaminolevulinate, MAL) is an effective and safe treatment option for actinic keratoses. Light-emitting diodes (LED) are suitable light sources for topical PDT. To evaluate the efficacy, painfulness, patient satisfaction and cosmesis of LED-based PDT a prospective, randomized and controlled split-face study was performed. Methods: Topical ALA-PDT was administered to 17 patients whose actinic ker-atoses (n = 131) were symmetrically distributed and suitable for a two-side comparison. After incubation with MAL (16%), irradiation was performed with the incoherent lamp (160 mW cm⁻²; 100 J cm⁻², PDT 1200L, Waldmann Medizintechnik, Villingen-Schwenningen, Germany) on one side and the LED system (120 mW cm⁻²; 40 J cm⁻², LEDA, WaveLight AG, Erlangen, Germany) on the other side. The patients were followed by re-evaluation up to 6 months. Results: Six months following treatment there was no significant difference between the infiltration and keratosis scores in both treatment regimes (p = 0.812). The remission rate was 78.5% (LED system) vs.80.3% (incoherent lamp). There was no significant difference between both light sources regarding the pain during therapy (p = 0.988). There was no significant difference between both treatment regimes regarding patient satisfaction (p = 1). Conclusions: LEDA-based MAL-PDT is an effective alternative for the treatment of atinic keratoses. The remission rates and cosmetic results are not inferior to PDT using incoherent light systems. Both treatment regimes are similarly painful.     

A new protocol and criteria for quantitative determination of sensitization potencies of chemicals by guinea pig maximization test

This paper presents precise sensitization test data of 15 chemicals with a wide spectrum of sensitization potencies, and proposes a new protocol and criteria for quantitative evaluation of sensitization potencies of chemicals. The tests were performed according to the design of Magnus-son and Kligman, changing the application concentrations for induction as well as for challenge phases. 3-dimensional relationships between mean response (or sensitization rate), induction and challenge concentrations were found in all chemicals tested. The following 2 values are proposed as a quantitative measure of sensitization potency: (a) the minimum induction concentration that induces a positive response; (b) the challenge concentration that induces a mean response approximately equal to 1.0 among the animals applied with the highest concentration for induction. Both values coincided with each other within the range of 1 order of magnitude in every compound except 2. The values varied by 5 orders or more of magnitude among the compounds, showing a wide variation of sensitization potencies among chemicals. A good correlation was found for every chemical between the value of sensitization potency thus obtained and the residual levels in causative products in human cases of allergic contact dermatitis. A new experimental protocol for obtaining values (a) and (b) is proposed.     

Efficacy of lasers and PDT for the treatment of acne vulgaris

Acne vulgaris can represent a therapeutic challenge in terms of managing ongoing symptoms and preventing scar formation. While the copious variations of available treatments address milder forms of the disease, until recently, therapies for resistant or moderate-to-severe forms were limited to systemic agents that were accompanied by potentially severe side-effects. With the addition of lasers, light sources, and aminolevulinic acid-photodynamic therapy (ALA-PDT) therapies, dermatologists may now have viable new alternatives for treating all grades of acne severity that circumvent the negative side-effects associated with many conventional options.