Home About us Contact
|
Home About us Contact | ||
|
|
||
Aminolaevulinic Acid (aminolaevulinic + acid)
Selected AbstractsEffect of transition metal ions (cobalt and nickel chlorides) on intestinal iron absorptionEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 9 2004G. O. Latunde-Dada Abstract Background, Haem biosynthesis may regulate intestinal iron absorption through changes in cellular levels of ,-aminolaevulinic acid (ALA), haem and perhaps other intermediates. CoCl2 and NiCl2 are activators of haem oxygenase, the rate-limiting enzyme in haem catabolism. Co2+ and Ni2+ may also regulate and increase iron absorption through a mechanism that simulates hypoxic conditions in the tissues. Design, We assayed intestinal iron absorption in mice dosed with CoCl2 or NiCl2. The effects of these metal ions on splenic and hepatic levels of ALA synthase and dehydratase as well as urinary levels of ALA and phosphobilinogen were also assayed. Results, While Co2+ enhanced iron absorption when administered to mice at doses of 65, 125 and 250 µmoles kg,1 body weight, Ni2+ was effective only at the highest dose. Ni2+ but not Co2+ at the highest dose reduced urinary ALA in the treated mice. Both metals ions increased splenic expression of haem oxygenase 1 and iron regulated protein 1, proteins involved, respectively, in haem degradation and iron efflux. Co2+ induced erythropoietin expression. Conclusions, The data suggest that while the effect of Ni2+ on iron absorption could be explained by effects on ALA, the effect of Co2+ may not be explained simply by changes in haem metabolism; therefore, effects mediated by alterations of specific haemoproteins by mechanisms that simulate tissue hypoxia could be important. [source] Photodynamic therapy: update 2006 Part 1: Photochemistry and photobiologyJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 3 2007PG Calzavara-Pinton Abstract Photodynamic therapy (PDT) is a two-step therapeutic technique in which the topical or systemic delivery of photosensitizing drugs is followed by irradiation with visible light. Activated photosensitizers transfer energy to molecular oxygen, generating reactive oxygen species (ROS). The subsequent oxidation of lipids, amino acids and proteins induces cell necrosis and apoptosis. In addition, ROS indirectly stimulate the transcription and release of inflammatory mediators. The photosensitizers are selective, in that they penetrate and accumulate in tumour cells or in the endothelium of newly formed vessels while generally avoiding the surrounding healthy tissue. The mechanisms of penetration through the cell membrane and the pattern of subcellular localization strongly influence the type of cellular effect. The photobiology and photoimmunology of the haematoporphyrin (Hp) derivative and its purified, lyophilized and concentrated form porfimer sodium have been investigated over the past 30 years. However, interest in PDT in dermatology was not raised until the 1990s with the availability of a simple and effective technique, the topical application of aminolaevulinic acid (ALA) and its methyl ester (methyl aminolaevulinate, MAL) followed by irradiation with broadband red light. At the same time, several new ,second-generation' synthetic sensitizers (e.g. benzoporphyrin derivatives, phthalocyanines, chlorins and porphycenes) became available. These compounds are chemically pure, highly efficient, selective and safe, while offering the advantage that the generalized skin photosensitivity they produce lasts for only a short time. They are currently under clinical evaluation but have not yet been approved for clinical use. This paper provides an overview of the chemistry of the photosensitizers, the photobiology and photoimmunology of the photodynamic reaction as well as the photophysical characteristics of the light sources available for PDT. [source] Disappointing results and low tolerability of photodynamic therapy with topical 5-aminolaevulinic acid in psoriasis.JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 7 2006A randomized, double-blind phase I/II study Abstract Background, Based on good results in the treatment of superficial skin tumours, since the early 1990s topical photodynamic therapy with aminolaevulinic acid (ALA PDT) has been used for disseminated, inflammatory dermatoses including psoriasis. However, there is still a lack of well-documented trials. Objective, A prospective randomized, double-blind phase I/II intrapatient comparison study was conducted in 12 patients to investigate whether topical ALA PDT is an effective treatment for chronic plaque-type psoriasis. Methods, In each patient three psoriatic plaques were randomly treated with a light dose of 20 J/cm2 and 0.1%, 1% and 5% ALA, respectively. Treatment was conducted twice a week until complete clearance or for a maximum of 12 irradiations. Therapeutic efficacy was assessed by weekly determination of the psoriasis severity index (PSI). Results, The mean percentage improvement was 37.5%, 45.6% and 51.2% in the 0.1%, 1% and 5% ALA-treated groups, respectively. Irradiation had to be interrupted several times because of severe burning and pain sensation. Conclusion, Topical ALA PDT did not prove to be an appropriate treatment option for plaque-type psoriasis due to disappointing clinical efficacy, the time-consuming treatment procedure and its unfavourable adverse event profile. [source] Photodynamic therapy with violet light and topical ,-aminolaevulinic acid in the treatment of actinic keratosis, Bowen's disease and basal cell carcinomaJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 6 2001AT Dijkstra Abstract Background Most clinical studies using photodynamic therapy (PDT) with topical application of ,-aminolaevulinic acid (,-ALA) use red light because it allows greater depth of penetration. However, given the porphyrin-like spectrum of ,-ALA-induced photosensitivity, violet light provides a maximal overlap with the excitation spectrum of protoporphyrin IX, meaning that PDT with violet light uses less light energy to induce the phototoxic reaction. Aim To study the efficacy of violet light in combination with topical ,-ALA PDT in the treatment of premalignant and malignant skin lesions. Methods Eight hours after 20%,-ALA was applied topically, photoirradiation was performed with an incoherent light source (Philips HPM-10, 400 W) emitting predominantly violet light (400,450 nm). Lesions received 10,20 J/cm2 during an exposure time of 30 min. The 38 subjects treated included three with basal cell naevus syndrome with multiple (> 30) superficial and nodular basal cell carcinomas (BCCs), one subject had multiple lesions of Bowen's disease, involving 50% of the scalp, and the remaining 34 subjects presented a total of 35 superficial BCCs, 10 nodular BCCs, four large solar keratoses and five solitary lesions of Bowen's disease. Results Complete remission both clinically and histologically was seen after a single treatment in 82% of the superficial BCCs (100% after a second treatment), 50% of the nodular BCCs, one of the four solar keratosis lesions (partial remission in the other three) and 90,100% of the solitary lesions of Bowen's disease. Conclusions ,-ALA PDT using violet light appears to be a well tolerated and effective alternative treatment for premalignant and malignant skin lesions, especially when there are multiple lesions or large patches comprising a large area of skin. [source] Topical aminolaevulinic acid- and aminolaevulinic acid methyl ester-based photodynamic therapy with red and violet light: influence of wavelength on pain and erythemaBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2009P. Mikolajewska Summary Background, Photodynamic therapy (PDT) is based on the combination of an exogenously administered precursor of photosensitizer [protoporphyrin IX (PpIX)] synthesis and exposure to light. Choosing the optimal wavelength is important. Red light penetrates deeper into tissue, while violet light is more efficient in activating PpIX but does not penetrate so deeply. Objectives, We studied PpIX formation and the PDT effect after application to human skin of creams containing aminolaevulinic acid (ALA) and aminolaevulinic acid methyl ester (MAL). The aim of the study was to investigate whether the wavelength of the light used has an influence on pain sensations during topical PDT with the different prodrugs. Methods, ALA cream (10%) and MAL cream (10%) were topically applied on the skin of 10 healthy volunteers. After 24 h the application site was exposed to 8 mW cm,2 violet laser or to 100 mW cm,2 red laser light. The erythema index was monitored up to 24 h after light exposure. For the first time the pain during topical ALA- and MAL-PDT was assessed by measuring the time taken for pain to occur. Also, for the first time, the intensities of the light sources were calibrated so as to have the same relative quantum efficiency. Results, The pain sensation during ALA-PDT with red light came 22 s sooner than during ALA-PDT with violet light, which is statistically significant (P < 0·05). Moreover, ALA-PDT with red light gave stronger and more persistent erythema than ALA-PDT with violet light. ALA induced about three times more PpIX than MAL. No statistically significant differences were found for erythema, or for the time for pain to occur, in the case of MAL-PDT with red vs. violet light. Conclusions, Topical ALA-PDT with violet light allows longer exposure times before pain is induced and gives less erythema as compared with topical ALA-PDT with red light. [source] Topical aminolaevulinic acid-based photodynamic therapy as a treatment option for psoriasis?BRITISH JOURNAL OF DERMATOLOGY, Issue 2 2005Results of a randomized, observer-blinded study Summary Background, Topical aminolaevulinic acid-based photodynamic therapy (ALA-PDT) has recently been tried in small open studies for several inflammatory dermatoses including psoriasis. Objectives, The purpose of this randomized, within patient comparison study was to investigate whether topical ALA-based PDT using a range of light doses can induce a satisfactory response in localized psoriasis. Patients and methods, Twenty-nine patients with chronic plaque type psoriasis were enrolled in the study. After keratolytic pretreatment three psoriatic plaques in each patient were randomly allocated to PDT with 1% ALA and a light dose of 5 J cm,2, 10 J cm,2 or 20 J cm,2, respectively. Treatment was performed twice weekly until complete clearance or for a maximum of 12 irradiations. As a measure of clinical response the psoriasis severity index (PSI) of the three target plaques was assessed separately by an observer blinded to the treatment at baseline, before each PDT treatment and 3,4 days after the last irradiation. Results, Eight patients withdrew prematurely from the study. Keratolytic pretreatment alone reduced the baseline PSI in all three dose groups by about 25%. Subsequent PDT with 20 J cm,2 resulted in a final reduction of PSI by 59%, PDT with the lower doses of 10 J cm,2 and 5 J cm,2 decreased the baseline PSI by 46% and 49%, respectively. The difference in clinical efficacy between 20 J cm,2 and 10 J cm,2 or 5 J cm,2 was statistically significant (P = 0·003; P = 0·02), whereas no difference was found between 10 J cm,2 and 5 J cm,2 (P = 0·4). All patients reported some degree of PDT-induced stinging or burning during irradiation. Conclusions, The unsatisfactory clinical response and frequent occurrence of pain during and after irradiation renders topical ALA-based PDT an inadequate treatment option for psoriasis. [source] Routine double treatments of superficial basal cell carcinomas using aminolaevulinic acid-based photodynamic therapyBRITISH JOURNAL OF DERMATOLOGY, Issue 6 2000J.C. Haller Background,Superficial basal cell carcinomas of the skin (sBCC) often respond poorly to single-treatment aminolaevulinic acid-based photodynamic therapy (ALA,PDT), with a number of reports indicating a relapse rate of 50% or more. Objectives,To determine whether a second treatment at seven days can improve the response. Methods,Twenty-six lesions were treated twice with ALA,PDT, with an interval of 7 days between the two treatment sessions. Results,We observed a complete response rate of 100% 1 month after treatment. Only one lesion relapsed (16 months post-PDT), a relapse rate of 4% (median follow up 27 months; range 15,45 months). Cosmetic results were excellent. Conclusions,We consider routine double treatments with ALA,PDT to be an effective approach to the management of sBCC, particularly those located in anatomically difficult, or cosmetically sensitive, sites. [source] Microbiological effect of photodynamic therapy (PDT) in healthy volunteers: a comparative study using methyl aminolaevulinate and hexyl aminolaevulinate creamCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 6 2007A. Yung Summary Background., Acne vulgaris is a common skin problem that affects up to 90% of adolescents. Colonization of the duct with Propionibacterium species is one of the factors implicated in the development of acne. Owing to the increasing incidence of antibiotic resistance, there has been an greater interest in the development of new methods to treat acne. Early studies have shown that photodynamic therapy (PDT) with aminolaevulinic acid (ALA) can lead to prolonged improvement in acne. Newer derivatives of ALA such as methyl aminolaevulinate hydrochloride (MAL) and hexyl aminolaevulinate hydrochloride (HAL) have been developed for use in PDT, with the potential benefits of higher lipophilicity and penetration potential. Objectives., To determine the microbiological effect and tolerability of a single application of HAL-PDT and to compare it with MAL-PDT in healthy volunteers. Methods., This was a randomised double-blind study to examine the microbiological effects and safety of a single application of MAL-PDT and HAL-PDT on normal skin in 18 healthy volunteers. Bacterial skin samples for Propionibacterium spp. and Micrococceae were obtained at baseline and 2, 4, 7 and 14 days. Results., Following PDT with MAL and HAL, a statistically significant transient reduction in mean density of Propionibacterium spp. 2 days after treatment using each agent (P < 0.05 for both) was found. There were no significant changes in mean number of Micrococceae for the duration of the study period. Treatment with HAL-PDT and MAL-PDT was well tolerated. Overall, HAL-PDT was associated with fewer side-effects compared with MAL-PDT (P < 0.01) over the 14 day study period. Conclusion., HAL-PDT and MAL-PDT transiently reduce density of Propionibacterium spp. density to a similar degree in normal healthy individuals. The transient reduction in Propionibacterium spp. suggests that the prolonged antiacne effect of PDT relies on factors independent of bacterial density. HAL-PDT appears to be better tolerated than MAL-PDT. [source] | ||||||||||