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PubMed1998

A chemical dosimeter for the determination of the photodynamic activity of photosensitizers.

Uric acid a known singlet oxygen scavenger, was investigated as a chemical dosimeter in physiological aqueous solution for use in photodynamic therapy. The uric acid test takes the decrease in uric acid (UA) absorbance at 293 nm after laser light irradiation of a solution containing UA and a photosensitizer as a rapid evaluation of relative photodynamic activities of the photosensitizer. A uric acid test standard procedure was defined. To compare photodynamic activity of different photosensitizers or irradiation conditions a proposal for a photodynamic activity scale based on the uric acid test is given. Examples of uric acid test operation are given by comparing the changes in UA absorbance decrease with respect to irradiation wavelength and to photosensitizer concentration of Photofrin II with that of two other photosensitizers (5,10,15,20-tetrakis-[4-hydroxyphenyl]-21H,23H-porphyrin (TOP) and 5,10,15,20-tetrakis-[4-carboxyphenyl)-21H, 23H-porphyrin (TCPP), both derivatized with methoxypolyethyleneglycol (TOP-MPV and TCPP-AMP) as a macromolecular carrier). The photodynamic activity of the three photosensitizers using the proposed photodynamic activity scale is given.

Dihematoporphyrin Ether↗
PubMed2005

[Assessment of the photosensitization potential of zinc gluconate].

INTRODUCTION: Tolerance and clinical efficacy of zinc gluconate are well documented, however, no study have evaluated its photosensitizing potential. It is well known that many treatments of acne are photosensitizing. Evaluation of the photosensitizing potential of zinc gluconate was the aim of this study. PATIENTS AND METHOD: Two open, monocentric studies were carried out with acneic volunteers. The methodology used in this study was an adaptation from that existing for the evaluation of the photosensitizing potential of topical products. In the study of phototoxic potential, volunteers were exposed to 20 J/cm2 UVA and to 0.75 times MED, before and after administration of zinc gluconate. Clinical and colorimetric evaluations of reactions were then carried out 1, 24, 48 and 72 hrs after exposure. In the photoallergic potential study, during the first week of the induction phase, the volunteers were exposed to 2 times MED, and to 3 times the MED during the second and third week. Then during the challenge phase, they were exposed t o4 J/cm2 UVA and to 0.75 times MED. Zinc gluconate was administered throughout the study. Clinical and colorimetric evaluations of reactions were carried out 24, 48 and 72 hrs after exposure, only during the challenge phase. RESULTS: The majority of clinical scores measured on scales at 6 and 5 levels were equal to 0 and 0.5 (evaluation of the phototoxic potential) or all equal to 0 (evaluation of the photoallergic potential). Thus zinc gluconate did not induce phototoxic or photosensitive reactions, whatever the ultraviolet type used. DISCUSSION: Since zinc gluconate does not induce any photosensitive reaction, it could be prescribed during periods of exposure to sun.

Acne Vulgaris↗
PubMed1987

Photosensitive psoriasis. An epidemiologic study.

In this study of photosensitivity among psoriasis patients, a questionnaire was mailed to 2000 psoriasis patients living within the service area of Karolinska Hospital, Stockholm. Of the 88% patients who replied, 4.4% stated that their psoriasis always worsened after sun exposure, and 7.3% stated that this was sometimes so. After telephone interviews with an 80% sample of these allegedly photosensitive patients, half of them were considered nonphotosensitive. Thus an estimated prevalence of 5.5% photosensitivity was obtained. Forty-three percent of the light-sensitive patients had a history of polymorphous light eruption with secondary exacerbation of psoriasis lesions. Comparison between the photosensitive and the nonphotosensitive patients concerning background factors and symptoms showed a statistically significant increase (p less than or equal to 0.001) in the photosensitive group concerning skin type I, psoriasis affecting hands, heredity for photosensitivity, and advanced age.

Adolescent↗
PubMed1986

[Photosensitivity in human pathology: mechanisms and clinical aspects].

Photosensitivity diseases are reviewed. The pathogenesis of photodermatoses is not completely elucidated, especially because the photosensitizing agents are rarely identified. In exogenous photosensitization, the chemical agent (chromophore) is most often identified, reaching the skin either via topical contact or by systemic administration (drugs). Concepts of phototoxicity (photochemical reaction) and photo-allergy (photo-immunologic reaction) explain the clinical aspects. Dermatoses with photosensitivity are divided into three groups: photo-aggravated dermatoses (solar herpes, lupus erythematosus), photosensitivity caused by protective system defect (xeroderma pigmentosum), and photosensitivity caused by metabolic defects (porphyrias, pellagra). Idiopathic photodermatoses (unknown chromophore) are triggered by solar exposure (systemic photo-allergens would serve as mediators): 'benign estival polymorphous light eruption', polymorphous light eruptions, persistent light reactor, solar urticaria.

Adult↗
PubMed1998

Eradication of Acinetobacter baumannii by photosensitized agents in vitro.

The photodynamic effects of photosensitizers on Acinetobacter baumannii were studied. These Gram negative bacteria have recently been implicated in various infections, mainly acquired in hospitals. They have outstanding characteristics of multidrug high resistance to antimicrobial agents. The best photodynamic effect was obtained when A. baumannii cultures were treated with light activated deuteroporphyrin (Dp) at a concentration of 34 mumoles l-off and polymyxin nonapeptide (PMNP) at a concentration of 200 mumoles l-1. At these concentrations the culture in brain heart infusion (BHI) broth was found to be sterile after l h of treatment. Some inhibition was also obtained under the same conditions with Cd-texaphyrin (Cd-Tx) in the presence of PMNP. Treatment with various other photosensitizers in the presence of PMNP exhibited only marginal antibacterial activity. The cationic photosensitizer tetra-methylpyridyl porphine (TMPyP) did not exhibit any photodynamic effect on A. baumannii when illuminated during its growth in BHI broth. Bacteria grown in nutrient broth or suspended in saline and treated by TMPyP resulted in a significant photoinactivation by the sensitizer alone even in the absence of PMNP. It was found that a high concentration of the proteins present in BHI or in serum prevent TMPyP from acting as a photosensitizer against A. baumannii. Bovine serum albumin at the same high protein concentration prevents Dp (in the presence of PMNP) to act as a photosensitizer. The anionic photosensitizer tetra-sulfonatophenyl porphine (TPPS4) did not show any photodynamic effect in high or low protein media. In this study it was found that despite the high resistance of the Acinetobacter baumannii to antibiotics, these bacteria can be significantly photoinactivated by treatment with either Dp + PMNP or TMPyP in low protein content environments. When the protein concentration is high photoinactivation efficiency depends on the type of protein present in the medium.

Acinetobacter↗
PubMed2001

Destruction of helminth eggs by photosensitized porphyrin.

Tunisian untreated wastewater exhibits an average of 30 human helminth eggs per litre. After treatment, the concentration decreases to one egg per litre, or more in some cases. The percentage removal cited for wastewater processes provides no real indication of the destruction of the organisms, but merely of their transfer to another medium. In this study, we report the use of an environmentally friendly photoactive compound for wastewater disinfection. Photosensitization involves the generation of very toxic short-lived species on absorption of light by porphyrin. Microorganism photosensitization is potentially useful for sterilization and for the treatment of certain bacterial diseases. Gram-positive bacteria can be photoinactivated by a range of photosensitizers, but Gram-negative bacteria are not usually susceptible to photosensitized destruction. Our findings clearly demonstrate that the cationic meso-substituted porphyrin, tetra-(4-N-methylpyridyl) porphin tetra-tosylate (T4MPYP), is an efficient photosensitizer of helminth eggs on visible light illumination. The microscopic observation of helminth eggs shows that many types of ultrastructural alterations are potentially associated with exposure to T4MPYP and an adequate intensity of light: morphological changes without breakage; small alterations of eggshells; complete destruction. The degree of egg alteration increases with both increasing T4MPYP concentration and irradiation time. Moreover, the dissolved oxygen concentration, water quality and the type of eggs can influence the sensitivity of helminth eggs to photosensitization. Indeed, suspended solids (turbidity) were the most influential solution parameter on the efficiency of the photochemical process.

Animals↗
PubMed2003

Spatial heterogeneity and temporal kinetics of photosensitizer (AlPcS2) concentration in murine tumors RIF-1 and MTG-B.

In this study we compared the photosensitizer concentration in two experimental murine tumors using an in situ fluorescence detection instrument to examine temporal and spatial variations, after intravenous versus intratumor injection. Also, the variations in the estimate as detected by large area sampling and micro-region sampling are compared, in order to determine what the inter-tissue and inter-animal variations are, and how the method of sampling affects this estimate. The latter study was carried out ex vivo in the same tumors, which had been harvested and frozen after in vivo measurements were made. The photosensitizer, disulphonated aluminum phthalocyanine (AlPcS2) was injected either intravenously (IV) or directly into the tumor (ITu), using two murine models, MTG-B (mammary adenocarcinoma) and RIF-1 (radiation-induced fibrosarcoma) grown subcutaneously on the flank. An in situ microsampling fluorescence probe was used to assess photosensitizer concentration, through real-time measurement of the remitted intensity. The photosensitizer concentration was evaluated at 8 time endpoints between 15 min and 48 h post-injection. Inter-tumor and intra-tumor variations were assessed by repeated samples from the tumor tissues. The average photosensitizer level reaches a peak between 3 to 6 h in both tumor and normal tissues using IV administration, but peaks within 1 h following ITu administration. MTG-B tumors demonstrated a factor of 2 higher uptake than RIF-1 tumors. The pharmacokinetic uptake rates of the RIF-1 tumor were 3 times faster than for MTG-B, while there was no statistical difference in their clearance rates. Preferential uptake of AlPcS2 by both tumors compared to contra-lateral flank subcutaneous normal tissue was documented, with ITu injection exceeding IV injection by a factor of 10 in the tumor to normal tissue ratio. Inter-animal standard deviation in the mean fluorescence was near 76% for both routes of administration, but estimates of the variation within tumor were near 16% standard deviation when a large sampling volume was used. In contrast, microscopic intra-tumor standard deviation in the mean estimate was near 76%, with IV injection, indicating that high heterogeneity exists in the photosensitizer concentration on a smaller distance scale. The inter-tumor variation was reduced by ITu injection, but at the expense of increasing intra-tumor variation.

Adenocarcinoma↗
PubMed2002

Photosensitized growth inhibition of cultured human skin cells: mechanism and suppression of oxidative stress from solar irradiation of glycated proteins.

Chronic exposure to sunlight plays a role in skin aging and carcinogenesis. The molecular mechanisms of photodamage by ultraviolet A, the sunlight's major ultraviolet constituent, are poorly understood. Here we provide evidence that advanced glycation end products on proteins are sensitizers of photo-oxidative stress in skin cells. Glycation is a process of protein damage by reducing sugars and other reactive carbonyl species leading to the formation of advanced glycation end products, which accumulate on long-lived proteins such as dermal elastin and collagen during skin aging. Growth inhibition as a result of advanced glycation end product photosensitization of ultraviolet A and solar-simulated light was demonstrated in human keratinocytes and fibroblasts. Using advanced glycation end product bovine serum albumin and advanced glycation end product collagen as model photosensitizers, ultraviolet A-induced formation of H2O2 was identified as the key mediator of skin cell growth inhibition as evidenced by complete protection by catalase treatment and equivalent growth inhibition of unirradiated cells treated with pre-irradiated advanced glycation end product protein. D-penicillamine protected against advanced glycation end product-photosensitized growth inhibition even when added following irradiation, suggesting the feasibility of therapeutic approaches for protection against skin ultraviolet A damage. Photosensitized growth inhibition increased with the degree of advanced glycation end product modification paralleled by the amount of H2O2 formed upon solar-simulated light irradiation of the protein. Photosensitization was not observed using bovine serum albumin modified with the major advanced glycation end product, Nepsilon-carboxymethyl-L-lysine, ruling out effects of cellular advanced glycation end product receptor (RAGE) stimulation. In contrast to bovine serum albumin, unglycated collagen showed photosensitization in CF3 fibroblasts and generation of H2O2 upon solar-simulated light irradiation. This study supports the hypothesis that advanced glycation end product-modified proteins are endogenous sensitizers of photo-oxidative cell damage in human skin by ultraviolet A-induced generation of reactive oxygen species contributing to photoaging and photocarcinogenesis.

Cell Division↗
PubMed1978

Galvanic skin response in photosensitive children.

Investigations of galvanic skin response under stress by different stimuli were carried out in 65 photosensitive and 70 non-photosensitive subjects aged 11--17 years. Photosensitive individuals at the age of 12--15 years showed a more pronounced skin reaction than non-photosensitive ones. The emotional reagibility (expressed by IE = (SEE TEXT), Traxel 1960, Stocksmeier and Langosch 1973) shows significantly higher values than in nonphotosensitive children. In addition to this, photosensitive subjects demonstrate a delayed habituation. Together with further results (Gross-Selbeck et al. 1976) the findings indicate that photosensitivity is not the isolated symptom of a genetically determined increased cerebral excitability, which can represent a factor in the pathogenesis of epilepsy for instance, but must be understood as a special characteristic of a particular constitution.

Adolescent↗
PubMed1999

Modification of DNA bases by photosensitized one-electron oxidation.

PURPOSE: To determine the distribution of base damage within isolated DNA upon oxidation by three type I photosensitizers in aerated aqueous solution. MATERIALS AND METHODS: Aqueous solutions of DNA were exposed to UVA in the presence of riboflavin, benzophenone or menadione. Then, eight modified nucleobases were measured, using HPLC-EC, GC-MS or HPLC with fluorescence detection. RESULTS: The three photosensitizers led to a predominant degradation of guanine bases within DNA. The relative yield of the three main guanine degradation products measured in DNA was similar with the three sensitizers. 8-OxodAdo was also produced in an almost constant yield with respect to its guanine analogue. The yield of oxidized pyrimidines was lower and was found to depend on the photosensitizer used. The results were compared with the yield of photosensitization-induced degradation of the 2'-deoxyribonucleosides. CONCLUSION: The favoured photosensitized degradation of guanine within DNA may be explained by its lower oxidation potential with respect to that of the other bases, together with the occurrence of charge transfer through DNA. The base modification pattern determined in the present work is different from that obtained upon reaction of hydroxyl radicals. Under the latter conditions, pyrimidine oxidation products were generated more efficiently than by photosensitized one-electron oxidation.

Benzophenones↗
PubMed1996

Porphyrin-mediated photosensitization has a weak tumor promoting activity in mouse skin: possible role of in situ-generated reactive oxygen species.

Reactive oxygen species (ROS) have been implicated in skin tumor promotion. Earlier, we showed that porphyrin-mediated cutaneous photosensitization results in the in situ generation of ROS. Recently, we have provided the first in situ evidence for the involvement of ROS in stage I tumor promotion. In this study we further show that in situ-generated ROS act as weak complete tumor promoters in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated mouse skin. Papillomas were induced in Swiss albino mice by a single topical application of DMBA as initiator. The promotion was achieved in these mice by the sustained generation of ROS through dihematoporphyrin ether (DHE)-mediated cutaneous photosensitization, which was done once every day (six times a week) for 24 weeks. The first appearance of visible papillomas could be recorded 24 weeks after the initiation. The highest tumor incidence of 60% occurred at a dose of 2.5 mg/kg body wt DHE. Increasing the dose of DHE produced a decrease in the incidence as well as in the number of papillomas. In contrast, the number of carcinomas/mouse increased with increasing dose of DHE. Histopathology of the tumor samples indicated the formation of in situ carcinoma also in skin. ROS generated through DHE-mediated photosensitization resulted in a approximately 3 fold induction of ODC activity 9 h after photosensitization. DHE-mediated photosensitization enhanced [3H]thymidine incorporation in cutaneous DNA in a dose-dependent manner. A maximum 5-fold induction of [3H]thymidine incorporation was observed at a dose of 10 mg/kg body wt DHE. The longer latency period, low incidence of tumor induction, low tumor yield and low induction of ODC activity as compared with TPA represent the weak but complete tumor promoting potential of in situ-generated ROS. The low tumor incidence and tumor yield observed at higher doses of DHE may be due to the ablation of tumors at early stages due to the strong photodynamic action of DHE.Our data indicate that porphyrin-mediated photosensitization has a weak tumor promoting effect in mouse skin and in situ-generated ROS may play an important role in the development of this response.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2006

Erythrosine is a potential photosensitizer for the photodynamic therapy of oral plaque biofilms.

OBJECTIVES: The purpose of this study was to evaluate the clinical plaque disclosing agent erythrosine as a photosensitizer in the photodynamic killing of the oral bacterium Streptococcus mutans grown as a biofilm. METHODS: S. mutans biofilms of 200 microm thickness were grown in a constant-depth film fermenter. In addition to determining localization of the photosensitizer within biofilms using confocal laser scanning microscopy (CLSM), we compared the bacterial killing efficacy of erythrosine with that of two well-characterized photosensitizers, methylene blue (MB) and photofrin. Incubations were carried out with each photosensitizer (22 microM), and irradiation was for 15 min using a 400 W white light source. RESULTS: The CLSM results showed that erythrosine is taken up into S. mutans biofilms, where it is associated with the biomass of the biofilm rather than the fluid-filled channels and voids. Comparison of the cell killing efficacy of erythrosine in S. mutans biofilms of different ages showed that erythrosine was 1-2 log(10) more effective at killing biofilm bacteria than photofrin and 0.5-1 log(10) more effective than MB. The results were statistically significant (P < 0.01). Photodynamic therapy (PDT) with all three photosensitizers was increasingly effective as biofilm age increased, suggesting that temporal changes in biofilm architecture and composition affect susceptibility to PDT. CONCLUSIONS: PDT using erythrosine as photosensitizer shows excellent potential as a treatment for oral plaque biofilms.

Biofilms↗
PubMed1989

Photosensitivity and anti-Ro (SS-A) antibodies in black patients with systemic lupus erythematosus (SLE).

Ninety-two patients with SLE, 36 black and 56 white, were studied prospectively for photosensitivity and anti-Ro (SS-A) and anti-La (SS-B) antibodies. Photosensitivity was found in 19% of black patients, compared to 71% of white patients (p = 0.001). Anti-Ro antibodies were found in 69% of black and 54% of white patients (p = 0.013). Photosensitivity was present in 87% of Ro-positive white patients and in 54% of Ro-negative white patients (p = 0.007). However, in black patients with SLE there was a strong negative association: 4% of Ro-positive patients were photosensitive while 55% of Ro-negatives were photosensitive (p = 0.001). This suggests that black SLE patients may possess a factor which 'blocks' photosensitivity, perhaps by preventing local tissue damage caused by the interaction of Ro antibodies and ultraviolet light.

Antibodies, Antinuclear↗
PubMed1993

Carotenoids in erythropoietic protoporphyria and other photosensitivity diseases.

Studies in bacteria, animals and humans have demonstrated that carotenoid pigments can prevent or lessen photosensitivity by endogenous photosensitizers such as chlorophyll or porphyrins, as well as by exogenous photosensitizers such as dyes (e.g., toluidine blue) or porphyrin derivatives. The carotenoids beta-carotene and canthaxanthin have been found to be effective in the treatment of the photosensitivity associated with EPP and certain other photosensitivity diseases. No serious toxicity has been reported from their use, although the use of canthaxanthin is not recommended because of its propensity to form retinal granules. The pigments perform their protective function by quenching excited species formed by the interaction of porphyrins or dyes, light and air, thereby preventing the cellular damage which leads to the symptoms of photosensitivity.

Adolescent↗
PubMed1993

Flavin-photosensitized monomerization of dimethylthymine cyclobutane dimer in the presence of magnesium perchlorate.

We have investigated the photosensitized monomerization of the cis,syn-cyclobutane dimer of 1,3-dimethylthymine using riboflavin tetraacetate and a 5-deazaflavin derivative as photosensitizer. Although little monomerization of the dimer is induced by photoexcitation of the flavins in the absence of any additives, the flavins can function as an efficient photosensitizer in the presence of magnesium perchlorate. Mechanistic studies involving spectroscopic, quantum-yield and flash-photolysis measurements demonstrated that the photosensitized monomerization exclusively proceeds through electron transfer from the dimer to the triplet flavins complexed with Mg2+. The effects of magnesium perchlorate are compared with those on the chloranil-photosensitized monomerization and also with the effects of HClO4 on the flavin-photosensitized reaction.

Flavins↗
PubMed1999

New photosensitizers for photodynamic therapy in gastroenterology.

Most applications of photodynamic therapy (PDT) in gastroenterology to date have used porfimer sodium as the photosensitizing agent. For destroying small lesions in the wall of the gastrointestinal tract in inoperable patients, it has proved to be most effective, but attempts to achieve circumferential mucosal ablation, as in the treatment of Barrett's esophagus, have led to a high incidence of strictures, and all patients have cutaneous photosensitivity, which can last up to three months. Two new photosensitizers are of particular interest to gastroenterologists. PDT with metatetrahydroxyphenyl chlorin produces a similar biological effect as PDT with porfimer sodium, but the light doses required are much smaller, and cutaneous photosensitivity lasts only two to three weeks. Further, it can be used with percutaneous light delivery to destroy localized pancreatic cancers. The photosensitizing agent 5-amino levulinic acid, converted in vivo into the photoactive derivative protoporphyrin IX, sensitizes the mucosa much more than the underlying layers. This makes it feasible to destroy areas of abnormal mucosa without damaging the underlying muscle and is, therefore, better for treating Barrett's esophagus. Detailed clinical studies are required to establish the real role of PDT with the use of these and other new photosensitizers.

Aminolevulinic Acid↗
PubMedDate not supplied

The involvement of serotonin (5-hydroxytryptamine) in photosensitive epilepsy.

Over the last decade, vigorous efforts have been made by neuroscientists to unravel the cellular and molecular basis of photosensitive Epileptogenic activities in the central nervous system (CNS). Many neurotransmitters are implicated in brain activities but the extent to which they participate in these activities needs to be clarified. This review discusses the involvement of serotonin (5-hydroxytryptamine, 5-HT) in photosensitive epilepsy. The biosynthesis, metabolism, and structural and functional distribution of serotonin in the brain, and the role of 5-HT, its precursors, metabolites, receptors, agonists, antagonists, and the enzymes of reaction in photosensitive epileptogenic activity with reference to 5-HT cortical density, are discussed. The effects of biosynthetic and metabolic impairments in the serotonergic system, and the extent to which they contribute to the elicitation of myoclonic phenomena, hallucination, impulsivity, and migraine (HIMM) in photosensitive epilepsy are critically reviewed, and supported by evidence from animal models of photosensitive epilepsy. This evidence is correlated with the clinical findings in human photosensitive epilepsy.

Epilepsies, Myoclonic↗
PubMed2001

Analysis of fluoroquinolone-mediated photosensitization of 2'-deoxyguanosine, calf thymus and cellular DNA: determination of type-I, type-II and triplet-triplet energy transfer mechanism contribution.

Fluoroquinolone (FQ) antibacterials are known to exhibit photosensitization properties leading to the formation of oxidative damage to DNA. In addition, photoexcited lomefloxacin (Lome) was recently shown to induce the formation of cyclobutane pyrimidine dimers via triplet-triplet energy transfer. The present study is aimed at gaining further insights into the photosensitization mechanisms of several FQ including enoxacin (Enox), Lome, norfloxacin (Norflo) and ofloxacin (Oflo). This was achieved by monitoring the formation of DNA base degradation products upon UVA-mediated photosensitization of 2'-deoxyguanosine, isolated and cellular DNA. Oflo and Norflo act mainly via a Type-II mechanism whereas Lome and, to a lesser extent, Enox behave more like Type-I photosensitizers. However, the extent of oxidative damage was found to be relatively low. In contrast, it was found that cyclobutane thymine dimers represent the major class of damage induced by Enox, Lome and Norflo within isolated and cellular DNA upon UVA irradiation. This striking observation confirms that FQ are able to promote efficient triplet energy transfer to DNA. The levels of photosensitized formation of strand breaks, alkali-labile sites and oxidative damage to cellular DNA, as measured by the comet assay, were confirmed to be rather low. Therefore, we propose that the phototoxic effects of FQ are mostly accounted for energy transfer mechanism rather than by Type-I or -II photosensitization processes.

Animals↗