Daylight photodynamic therapy versus cryosurgery for the treatment and prophylaxis of actinic keratoses of the face - protocol of a multicenter, prospective, randomized, controlled, two-armed study.

BACKGROUND: Photodynamic therapy with daylight (DL-PDT) is efficacious in treating actinic keratosis (AK), but the efficacy of field-directed, repetitive DL-PDT for the treatment and prophylaxis of AK in photodamaged facial skin has not yet been investigated. METHODS/DESIGN: In this multicenter, prospective, randomized, controlled, two-armed, observer-blinded trial, patients with a minimum of 5 mild-to-moderate AK lesions on photodamaged facial skin are randomly allocated to two treatment groups: DL-PDT with methyl aminolevulinate (MAL) and cryosurgery. In the DL-PDT group (experimental group), 5 treatments of the entire face are conducted over the course of 18 months. After preparation of the lesion and within 30 min after MAL application, patients expose themselves to daylight for 2 h. In the control group, lesion-directed cryosurgery is conducted at the first visit and, in the case of uncleared or new AK lesions, also at visits 2 to 5. The efficacy of the treatment is evaluated at visits 2 to 6 by documenting all existing and new AK lesions in the face. Cosmetic results and improvement of photoaging parameters are evaluated by means of a modified Dover scale. Primary outcome parameter is the cumulative number of AK lesions observed between visits 2 and 6. Secondary outcome parameters are complete clearance of AK, new AK lesions since the previous visit, cosmetic results independently evaluated by both patient and physician, patient-reported pain (visual analogue scale), patient and physician satisfaction scores with cosmetic results, and patient-reported quality of life (Dermatology Life Quality Index). Safety parameters are also documented (adverse events and serious adverse events). DISCUSSION: This clinical trial will assess the efficacy of repetitive DL-PDT in preventing AK and investigate possible rejuvenating effects of this treatment. (Trial registration: ClinicalTrials.gov Identifier: NCT02736760). TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02736760 . Study Code Daylight_01. EudraCT 2014-005121-13.

Photodynamic therapy using intense pulsed light for treating actinic keratoses and photoaged skin of the dorsal hands: a randomized placebo-controlled study.

BACKGROUND: The efficacy of photodynamic therapy (PDT) with intense pulsed light (IPL) has been shown for treating actinic keratoses (AK) and improving photoaged skin on the face but not yet on the dorsal hands. OBJECTIVES: To evaluate the efficacy of PDT with IPL for treating AK of the dorsal hands, inducing neocollagenesis and improving photoaged skin. METHODS: In this prospective, randomized, placebo-controlled, monocentric, within-patient, observer-blinded trial, patients with one to four mild-to-moderate AK on the dorsal hands were randomly allocated to two different treatment groups: methyl aminolaevulinate (MAL) and IPL (λ ≥ 600 nm, 16·2 J cm-2 , three passes, Ellipse Flex PPT) (MAL-IPL) or placebo and IPL (λ ≥ 600 nm, 16·2 J cm-2 , three passes, Ellipse Flex PPT) (placebo-IPL). Patients received three treatments at 6-week intervals, and follow-up was 10 weeks after the last treatment. Thirty-seven patients aged 68·84 ± 9·28 years were randomized. The primary study end points were complete AK clearance per hand and neocollagenesis of subepidermal collagen 10 weeks after the last treatment. RESULTS: Ten weeks after the last treatment, complete AK clearance rates per hand were 54·5% after MAL-IPL and 3·0% after placebo-IPL (P < 0·0001); complete AK clearance rates per lesion were 69% and 15%, respectively (P < 0·001). The thickness of the subepidermal collagen band had increased by 290·6% (± 327·4%, P < 0·001) after MAL-IPL and by 215·5% (± 215·3%, P < 0·001) after placebo-IPL without any significant difference between the two groups. Ratings regarding mottled pigmentation and overall appearance by the blinded investigator were significantly higher for MAL-IPL than for placebo-IPL. Wrinkle size (MAL-IPL, -23·5%, P = 0·006; placebo-IPL, -17·7%, P = 0·010) and skin roughness (MAL-IPL, -18·3%, P < 0·001; placebo-IPL, -12·4%, P = 0·009) were significantly reduced in both groups without any significant difference between the two groups. CONCLUSIONS: On the dorsal hands, MAL-IPL reduced AK more efficaciously than placebo-IPL; both treatment modalities significantly improved photoaged skin.

Polymer adsorption on reconstructed Au(001): a statistical description of P3HT by scanning tunneling microscopy and coarse-grained Monte Carlo simulations.

We report on a combined theoretical and experimental characterization of isolated Poly(3-hexylthiophene) (P3HT) chains weakly adsorbed on a reconstructed Au(001) surface. The local chain conformations of in situ deposited P3HT molecules were investigated by means of scanning tunneling microscopy. For comparison, Monte Carlo simulations of the system were performed up to a maximum chain length of 60 monomer units. The dependence of the end-to-end distance and the radius of gyration on the polymer chain length shows a good agreement between experiment and Monte Carlo simulations using simple updates for short chains.

Fractional carbon dioxide laser resurfacing of rhytides and photoageing: a prospective study using profilometric analysis.

BACKGROUND: Results of profilometric skin analyses after fractional ablative skin resurfacing are not only important for evaluating the efficacy of this therapy but are also relevant for physicians practising laser and aesthetic skin therapy. Currently, objective measurements of wrinkle reduction after fractional CO2 laser resurfacing are scarce, and it remains unclear whether the various facial areas respond differently to this therapy. OBJECTIVES: To measure wrinkle parameters, the homogeneity of melanin distribution and skin roughness in four facial areas (periorbital, perioral, forehead, cheeks) before and after three fractional CO2 laser treatments. METHODS: Twenty-five women were analysed with regard to wrinkle parameters and mottled pigmentation on the face. We measured wrinkle size, depth and width and the homogeneity of melanin distribution and skin roughness in four facial areas before and after three fractional CO2 laser treatments. Additionally, the investigators rated clinical improvement using five-point grading scales. RESULTS: Wrinkles were significantly reduced in all facial areas, and the best results for wrinkle size and depth were found for the cheeks (-58·3%, P = 0·018 and -51·3%, P = 0·018) and the periorbital area (-35·1%, P < 0·001 and -31·1%, P = 0·001, respectively). The percentage improvements of rhytides evaluated by the investigators were mostly similar to those found from in vivo measurements. The homogeneity of melanin distribution in the skin was improved by 21·4% on the cheeks (P = 0·012) and by 24·0% in the periorbital area (P < 0·001). Clinical investigators rated the improvement of mottled pigmentation considerably higher (51-75%). CONCLUSIONS: After a serial treatment with the fractional CO2 laser, we measured considerably varying wrinkle reduction depending on the area of the face, and the best results were found for the cheeks.

[New developments in photodynamic therapy]. / Neue entwicklungen in der photodynamischen therapie.

We review new developments in recent years in photodynamic therapy. Since 2009 two new photosensitizers, a self-adhesive 5-aminolevulinic acid (ALA) patch and a nanoemulsion formulation of 5-aminolevulinic acid have been approved for the treatment of actinic keratoses. Pretreatment with ablative fractional lasers enhances penetration of the photosensitizer and enables intensified PDT in acral lesions and in field-cancerized skin. Several clinical trials have demonstrated the skin-rejuvenating effects of photodynamic therapy, while the underlying mechanisms of action have been clarified. The efficacy of photodynamic therapy has been shown in the treatment and prophylaxis of actinic keratoses in organ transplant recipients at high risk for developing skin cancer. We also summarize the results of available studies on daylight-mediated photodynamic therapy.

Clinical, histopathological and immunohistochemical assessment of human skin field cancerization before and after photodynamic therapy.

BACKGROUND: The field cancerization concept in photodamaged patients suggests that the entire sun-exposed surface of the skin has an increased risk for the development of (pre)-malignant lesions, mainly epithelial tumours. Topical photodynamic therapy (PDT) is a noninvasive therapeutic method for multiple actinic keratosis (AK) with excellent outcome. OBJECTIVES: To evaluate the clinical, histological and immunohistochemical changes in human skin with field cancerization after multiple sessions of PDT with methyl-aminolaevulinate (MAL). METHODS: Twenty-six patients with photodamaged skin and multiple AK on the face received three consecutive sessions of MAL-PDT with red light (37 J cm(-2)), 1 month apart. Biopsies before and 3 months after the last treatment session were taken from normal-appearing skin on the field-cancerized area. Immunohistochemical stainings were performed for TP-53, procollagen-I, metalloproteinase-1 (MMP-1) and tenascin-C (Tn-C). RESULTS: All 26 patients completed the study. The global score for photodamage improved considerably in all patients (P < 0·001). The AK clearance rate was 89·5% at the end of the study. Two treatment sessions were as effective as three MAL-PDT sessions. A significant decrease in atypia grade and extent of keratinocyte atypia was observed histologically (P < 0·001). Also, a significant increase in collagen deposition (P = 0·001) and improvement of solar elastosis (P = 0·002) were noticed after PDT. However, immunohistochemistry showed only a trend for decreased TP-53 expression (not significant), increased procollagen-I and MMP-1 expressions (not significant) and an increased expression of Tn-C (P = 0·024). CONCLUSIONS: Clinical and histological improvement in field cancerization after multiple sessions of MAL-PDT is proven. The decrease in severity and extent of keratinocyte atypia associated with a decreased expression of TP-53 suggest a reduced carcinogenic potential of the sun-damaged area. The significant increase of new collagen deposition and the reduction of solar elastosis explain the clinical improvement of photodamaged skin.

Photodynamic therapy for photorejuvenation and non-oncologic indications: overview and update.

Topical photodynamic therapy (PDT) has shown to be effective in the treatment and prevention of non-melanoma skin cancer. PDT is also established as treatment modality for several non-oncologic indications. The aesthetic effects of PDT for photoaged skin are well documented. An improvement of lentigines, skin roughness, sallow complexion and fine wrinkles was demonstrated. A reduction of histological signs of photoaging as a decrease of elastotic material and expression of p53 together with induction of neocollagenesis was shown. The possible contemporaneous treatment of non-melanoma skin cancer renders PDT a novel and effective technique for skin rejuvenation. Controlled studies also demonstrated the efficacy of PDT in the treatment of acne vulgaris and HPV-induced skin diseases as verrucae vulgares and condylomata acuminata. In addition, there is evidence that certain sclerosing, inflammatory, granulomatous and infectious skin diseases may profit from PDT. In contrast to PDT of tumours, where cellular destruction is the main goal of the therapy, in PDT of inflammatory skin conditions it is probably the modulation of cellular functions that plays the main role.

Skin ageing.

Similar to the entire organism, skin is subject to an unpreventable intrinsic ageing process. Additionally, skin ageing is also influenced by exogenous factors. Ultraviolet radiation in particular results in premature skin ageing, also referred to as extrinsic skin ageing or photoageing, which is the main cause of the changes associated with the ageing process in sun-exposed areas. Despite their morphological and pathophysiological differences, intrinsic and extrinsic ageing share several molecular similarities. The formation of reactive oxygen species and the induction of matrix metalloproteinases reflect the central aspects of skin ageing. Accumulation of fragmented collagen fibrils prevents neocollagenesis and accounts for the further degradation of the extracellular matrix by means of positive feedback regulation. The importance of extrinsic factors in skin ageing and the detection of its mechanisms have furthered the development of various therapeutic and preventive strategies.

Aesthetic effects of topical photodynamic therapy.

Topical photodynamic therapy has shown to be effective for the treatment of several aspects of skin ageing. Multiple studies have demonstrated improvement of fine wrinkles, mottled hyperpigmentation, tactile roughness and sallowness. These results are supported by immunohistochemical analysis that revealed both upregulation of collagen production and increased epidermal proliferation. Neocollagenesis as an indirect dermal effect of photodynamic therapy is stimulated through cytokine induction. This article reviews the available literature for photodynamic rejuvenation while discussing cosmetic effects, light sources, adverse effects and the mechanism of action.

[Skin and eyes]. / Haut und Auge.

Numerous diseases affect both skin and eyes due to similar ontogenetic origin. The eye is the second most common site of melanoma after the skin. The eyelids are predisposed for development of toxic and allergic dermatitis as the skin in this region is four times thinner than the other facial skin. The differential diagnosis must include atopic and seborrhoeic eyelid dermatitis. Atopic and vernal keratoconjunctivitis are associated with atopic eczema. Various immunobullous disorders involve the conjunctiva with varying severity. Side effects of dermatologic treatments with glucocorticoids, antimalarials, psoralens, retinoids, or tetracyclines may involve the eye.

[Skin aging]. / Hautalterung.

Like the entire human organism, the skin is subject to an intrinsic unpreventable aging process. But exogenous factors also influence skin aging. Ultraviolet radiation in particular results in premature skin aging, also referred to as extrinsic skin aging or photo aging, causing in large part aging-associated changes in sun-exposed areas. Intrinsic and extrinsic aging share several molecular similarities despite morphological and pathophysiological differences. The formation of reactive oxygen species and the induction of metalloproteinases reflect central aspects of skin aging. Accumulation of fragmented collagen fibrils prevents neocollagenesis and accounts for further degradation of extracellular matrix by means of positive feedback regulation. The importance of extrinsic factors in skin aging and the detection of its mechanisms has given rise to development of various therapeutic and preventive strategies.

[Skin and eyes]. / Haut und Auge.

Numerous diseases affect both skin and eyes due to similar ontogenetic origin. The eye is the second most common site of melanoma after the skin. The eyelids are predisposed for development of toxic and allergic dermatitis as the skin in this region is four times thinner than the other facial skin. The differential diagnosis must include atopic and seborrhoeic eyelid dermatitis. Atopic and vernal keratoconjunctivitis are associated with atopic eczema. Various immunobullous disorders involve the conjunctiva with varying severity. Side effects of dermatologic treatments with glucocorticoids, antimalarials, psoralens, retinoids, or tetracyclines may involve the eye.

In vitro and in vivo comparison of two different light sources for topical photodynamic therapy.

BACKGROUND: Photodynamic therapy (PDT) with 5-aminolaevulinic acid (ALA) is an effective and safe treatment option for the treatment of actinic keratosis (AK). Incoherent lamps are often used, matching the absorption maxima of ALA. OBJECTIVES: A comparative trial was performed to evaluate the efficacy of recently developed light-emitting diodes (LEDs). METHODS: Human epidermal keratinocytes were incubated for 24 h with ALA (100, 200, 300, 400 or 500 micromol L(-1)) and irradiated consecutively using either an incoherent halogen lamp (lambda(em) = 580-750 nm; 24 J cm(-2); 40 mW cm(-2)) or an LED system (lambda(em) = 633 +/- 3 nm; 3, 6, 12 or 24 J cm(-2); 40 mW cm(-2)). Topical ALA-PDT was performed on 40 patients with AK (n = 584) in a symmetrical distribution suitable for two-sided comparison. After incubation with ALA (20% in cream base) irradiation was performed with the incoherent lamp (100 J cm(-2); 160 mW cm(-2)) on one side and the LED system (40 J cm(-2); 80 mW cm(-2)) on the opposite side followed by re-evaluation up to 6 months. RESULTS: No significant differences between the LED system (3, 6, 12 or 24 J cm(-2)) and the incoherent light source (24 J cm(-2)) regarding cytotoxicity was found in vitro. The complete remission rate yielded in the in vivo investigation was also not significantly different at 6 weeks (P = 0.95), 3 months (P = 0.75) and 6 months (P = 0.61) following therapy. Six weeks following therapy complete remission rates of 84.3% (LED system) and 82.8% (incoherent lamp) were achieved. There was also no significant difference between both light sources regarding pain during light treatment (P = 0.67), patient satisfaction (P = 1.0) or cosmesis (P = 1.0) following therapy. CONCLUSIONS: These results show the efficacy of an LED system for ALA-PDT both in vitro and in vivo. ALA-PDT with the LED system showed a noninferiority regarding the clinical outcome in the treatment of AK compared with the incoherent lamp.

A trail pheromone component of the ant Mayriella overbecki Viehmeyer (Formicidae: Myrmicinae).

The myrmicine ant Mayriella overbecki lays recruitment trails during foraging and nest emigrations. The trail pheromone originates from the poison gland. From ten identified components of the poison gland secretions only methyl 6-methylsalicylate 1 elicited trail following behavior.

The production of recombinant proteins in transgenic barley grains.

The grain of the self-pollinating diploid barley species offers two modes of producing recombinant enzymes or other proteins. One uses the promoters of genes with aleurone-specific expression during germination and the signal peptide code for export of the protein into the endosperm. The other uses promoters of the structural genes for storage proteins deposited in the developing endosperm. Production of a protein-engineered thermotolerant (1, 3-1, 4)-beta-glucanase with the D hordein gene (Hor3-1) promoter during endosperm development was analyzed in transgenic plants with four different constructs. High expression of the enzyme and its activity in the endosperm of the mature grain required codon optimization to a C+G content of 63% and synthesis as a precursor with a signal peptide for transport through the endoplasmic reticulum and targeting into the storage vacuoles. Synthesis of the recombinant enzyme in the aleurone of germinating transgenic grain with an alpha-amylase promoter and the code for the export signal peptide yielded approximately 1 microgram small middle dotmg(-1) soluble protein, whereas 54 microgram small middle dotmg(-1) soluble protein was produced on average in the maturing grain of 10 transgenic lines with the vector containing the gene for the (1, 3-1, 4)-beta-glucanase under the control of the Hor3-1 promoter.

Bimolecular OH rate constants of organic compounds in solution. 2. Measurements in 1,2,2-trichlorotrifluoroethane using hydrogen peroxide as an OH source.

Semivolatile organic compounds (SOC) occur in the troposphere either adsorbed at aerosol particles or in the free gas phase, depending on temperature, vapor pressure of the compound, and total particular surface. In order to estimate the abiotic degradation of such compounds, the OH reaction rate constant must be known, which cannot be measured directly in the gas phase at the relevant temperature due to experimental difficulties. In the method proposed here, the inert solvent 1,1,2-trichlorotrifluoroethane is used as the reaction medium and hydrogen peroxide as photolytic OH source. Relative reaction rates can be measured, using a reference compound of known kOH air. The relative rates can be converted into absolute ones due to the 1:1 relationship observed by Dilling, Gonsior, Boggs, and Mendoza (1988) Environ. Sci. Technol. 22, 1447-1453, between the relative rates in the inert solvent and those in the gas phase.

Bimolecular OH rate constants of organic compounds in solution. 1. Measurements in water using hydrogen peroxide as an OH source.

A method of measuring relative kOH rate constants in water is described. OH radicals are created by photolysis of H2O2, using a Hg high-pressure lamp. Test and reference substances are irradiated for several hours in dilute, aqueous solutions containing 0.1 to 1.0% H2O2. The relative rate constants are determined from the decay of test and reference substances as a function of time, as measured by chemical analysis. Using the known kOH of reference substances, absolute kOH data for test substances are obtained. The following rate constants at 298 K have been measured (liter mol-1 sec-1): kOH (isopropanol) = 2.7 x 10(9) (relative to kOH (methanol) = 8.46 x 10(9]; kOH (toluene) = 6.0 x 10(9); and kOH (p-xylene) = 4.5 x 10(9) (relative to kOH (benzene) = 7.8 x 10(9]. The stationary OH concentrations are on the order of 5 x 10(-14) mol/liter. The kinetics of H2O2 photolysis is discussed, including the estimation of OOH/O2- concentrations during irradiation.

Testing of the abiotic degradation of chemicals in the atmosphere: the smog chamber approach.

Methods for measuring the hydroxyl-, ozone-, and direct photochemical reactivity of a substance in one specially designed medium size smog chamber are described. Rate coefficients for the reaction of OH with n-hexane, n-heptane, ethene, ethyne, chloroform, trichloroethene, methanol, 2-propanol, benzene, o-xylene, 1,4-dichlorobenzene, 1,2,4-trichlorobenzene, p-chloroaniline, naphthalene, acenaphthene, 1,4-dichloronaphthalene, biphenyl, and fluorenone are given and discussed. An upper limit of 5 X 10(-13) cm3/sec is given for the sum penta- and hexa-chlorobiphenyls (PCB). Rate coefficients for the ozone reaction are given for beta-pinene, limonene, delta 3-carene, cineol, vinyl chloride and 1,3-butadiene. In cases where the literature data are available for comparison, the rate coefficients (kappa OH and kappa O3) reported here compare favorably with the best data reported. The direct photochemical reactivity has been shown to be measurable if the chamber is cleaned carefully. Preliminary results on benzophenone are reported. The methods described here, except that of direct photochemical reactivity, are in agreement with those proposed to OECD. Moreover, part of the Draft OECD Test Guideline (Berlin, 1987) on "Photochemical-Oxidative Degradation in the Atmosphere" is based on work described here and on closely related work in other laboratories (Becker et al., 1984).

Improved control of non-insulin-dependent diabetes mellitus by combined halofenate and chlorpropamide therapy.

Combined halofenate-chlorpropamide was evaluated for the treatment of NIDDM. Four subjects treated with 500 mg/day chlorpropamide were given 500-1000 mg halofenate daily for 48 wk or longer. Fasting plasma glucose fell from 210 +/- 16 (+/- SEM) (11.67 +/- 0.89 mM) to 107 +/- 10 mg/dl (+/- SEM) (5.94 +/- 0.55 mM), P less than 0.005. Twelve additional subjects were entered into a 16-wk double-blind study testing chlorpropamide plus either placebo or halofenate. In the halofenate group, the mean fasting glucose fell from 227 +/- 27 (+/- SEM) (12.61 +/- 1.50 mM) and reached 107 +/- 19 mg/dl (+/- SEM) (5.94 +/- 1.06 mM) during the fourth month, whereas the placebo groups showed a decrease from 242 +/- 22 (+/- SEM) to 208 +/- 29 mg/dl (+/- SEM) (P less than 0.005). In addition, halofenate reduced the height of postprandial glycemic excursions by lowering fasting plasma glucose. When halofenate was used as the only therapy, reduction in fasting plasma glucose was small [179 +/- 12 reduced to 142 +/- 8 mg/dl (+/- SEM); 9.94 +/- 0.67 mM and 7.89 +/- 0.44 mM], P less than 0.05.