J Moan

..Our aim was to investigate the photostability of seven commercial sunscreen products after natural UV exposure (UVnat) and artificial UV exposure (UVart)...

..The seasonal effect was slightly, but not significantly, better for the younger than for the older age group. The effect was similar for all three geographical regions, irrespective of SCC incidence...

..The latter activation energy was within the error limits similar to that for the activity of the enzyme porphobilinogen deaminase, suggesting that this enzyme might represent a rate-limiting step for PpIX production in living tissue...

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..Light exposure slightly increased the rate of loss of PpIX from WiDr cells...

..Comparisons of skin cancer data from Norway and Australia/New Zealand indicate that squamous cell carcinoma and basal cell carcinoma are mainly related to annual solar UVB fluences, while UVA fluences play a larger role for CMM...

..In view of this, short, nonerythemogenic exposures around noon should be recommended rather than longer nonerythemogenic exposures in the afternoon. This would give a maximal yield of vitamin D at a minimal CMM risk...

..One possible interpretation of the present data is that, the level of calcidiol, or its derivative calcitriol (1alpha,25-dihydroxyvitamin D3, 1alpha,25-(OH)2D3), may act positively in concert with conventional therapies of colon cancer...

..The esters seem to penetrate less into the circulation than ALA, and PpIX formed by them in the skin is faster cleared than PpIX formed from ALA. This is also true after oral and i.p. administration of the drugs...

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..These data indicate that targeting both neoplastic cells and stroma with ALA and Pf (a low dose) can potentiate antitumor PDT effect with no risk of prolonged skin photosensitivity...

..The decay rate was slightly faster after systemic application than after topical application of ALA, but did not depend on the time (1-8 h) between application and analysis...

..Our results provide a theoretical basis for possible clinical use of ultrasound-combined ALA or ALA based photodynamic therapy...

..Traces of a photoproduct(s) with fluorescence emission slightly blue-shifted compared with that of PpIX, supposedly water-soluble porphyrins, were also detected after light exposure...

..ALA-induced porphyrins are transported away from the treated area and partly deposited in remote skin sites...

..The degree of bystander effect was higher for cells dying by necrosis than for cell dying by apoptosis...

..Despite extensive investigations, the differences in biodistribution and pharmacokinetics of protoporphyrin IX (PpIX) induced by ALA and its derivatives are still not well understood, notably for humans...

..Our findings clearly indicate some kind of cooperativity between cells treated with Photofrin and light...

..The stratum corneum may bind the esters temporarily, and slow down their penetration into the living cells where PpIX is formed...

..Photodynamic inhibition of enzymatic cell detachment may be related to PDT-induced inhibition of tumour metastasis...

..However, MAL-based PDT is not very efficient for poorly differentiated skin carcinoma. Thus, novel strategies to enhance the PDT effect are needed...

..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...

..This, together with the results from the different application times and concentrations indicates that ALAHE diffuses more slowly across the stratum corneum than ALA...

..The results suggest that the increased susceptibility to photoinactivation of Photofrin-sensitised tumours may be due to MMC-induced accumulation of the tumour cells in S-phase...

..The difference in mode of cell death for the different cell densities was not related to any observable difference in subcellular localization pattern of TPPS4 at equitoxic doses of photodynamic treatment...

..Furthermore, they are much better photosensitizers in a cellular system than are crude Hpd or Photofrin II, and, like the components of Hpd, they are taken up and retained by cells according to their degree of non-polarity...

..During light exposure a fluorescent product is formed in the cells with fluorescence excitation and emission characteristics similar to those of the "age pigment" lipofuscin (lambda exc = 350 nm, lambda em = 440 nm)...

..The fluorescence excitation spectra calculated for the depth 1.1 mm obtained the best fit with the experimentally measured spectra after topical application of ALA...

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..All these differences are related to difference in the spectra of the lamps. Thus, PDT light sources with emissions that are visually similar have significantly different photobiological properties...

..The fluorescence of Ppp was bleached during 670 nm light exposure. Exposure of Ppp at 670 nm gives no PpIX back. Thus, the phototransformation of PpIX to Ppp is probably not a reversible process...

..The ferrochelatase inhibitor dihydropyridine 3,5-diethoxycarbonyl-1,4-dihydrocollidine reduced the accumulation of PpIX in both cell lines...

..For the population as a whole sun exposure during vacations to sunny countries has so far been of minor importance in skin cancer induction...

..Practically no PpIX was formed in the skin as long as skin temperature was kept low (12 degrees C)...

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..6. With respect to cell uptake and retention of the dyes, the data did not show any uniform relationship to the polarity of the drugs, in contrast to what has been found earlier for Hp diethers of linear hydrocarbons...

..But for long application times and high concentrations, systemic effect of ALA applied topically on relatively large areas should be considered...

..Based on our results we suggest that calcidiol concentration at the time of cancer diagnosis is related to survival and discuss briefly ways to improve the vitamin D levels in the general population...

..The average length of these DNA fragments was found to be 155 kilobases (kb)...

..g., in gene therapy, vaccination, and cancer treatment...

..Complex processes, including changes in cellular shape and reorganization of the cytoskeleton, are suggested to participate in the observed ALA-PDT effect on the cell adhesion...

..The tumor localizing properties of mTHPP and mTHPC reported in the literature appear to be due to factors other than pH-dependent changes in the lipophilicity of the drugs...

..The kinetic patterns of uptake, retention and localisation of A1PcS2 and A1PcS4 are roughly correlated with their photodynamic effect on the tumour and normal skin...

..This finding indicates a new PDT modality that can be further developed for treatment of superficial melanotic melanomas and possibly other diseases where pigmentation is a problem...

..Seasonal and gender variations in Vitamin D level have been estimated from the analyses...

..The present work indicates that tumor selectivity of dyes, which get more lipophilic with decreasing pH value, may be related to the low extracellular pH value...

..The excitation spectrum of these products resembled that of hypericin. Hypericin appears to be more photostable than most sensitizers used in PDT, including mTHPC and Photofrin...

..364, 95% CI, -0.15 to 0.87; P = 0.025) for patients younger than 30 years. This finding may be related to higher endogenous levels of vitamin D in autumn, with a favourable influence on the conventional therapy...

..Application of tetraethylammonium chloride did not affect the cellular uptake of any of the photosensitizers. We conclude that the pH dependent uptake of photosensitizers is not mainly related to altered transmembrane potential...

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..More recently, both prostate cancer incidence and mortality have been shown to increase with increasing latitude, which probably relates to photosynthesis of vitamin D...

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..Numerous microvilli present on the surface of WiDr cells indicated marked uncertainties in cell surface area estimations. This gives large uncertainties in the real surface charge densities of cells...

..Further studies are needed to evaluate the role of PpIX induced by iron chelators used, against photoaging and cancer prevention...

..However, melanomas may arise also on non-sun-exposed areas (uveal and mucosal melanomas) and little is known about a possible relationship between sun exposure and melanoma on such locations...

..On the other hand, the LDL binding capacity for a drug is suggested to be a good index for cellular uptake. Such an index does not necessarily imply that the actual uptake occurs by the LDL pathway...

..The present data seem to favour the latter mechanism. Folic acid may have a role as an adjuvant in photodynamic therapy with systemically administered ALA and its derivatives...

..Thus, the photodynamic effect with 5-aminolevulinic acid may be enhanced by heating the tumour area before, and by cooling it immediately after the treatment...

..The overall data support our earlier hypothesis that season of diagnosis and therapy start improves the survival for breast cancer...

..It is known that folic acid, a synthetic form of folate, is degraded by UV radiation. We have also found that the most common folate derivative in the human body, 5-methyltetrahydrofolate, is UV sensitive...

..In view of these calcitriol and calcidiol data, the seasonal variation of cancer survival may be related to the calcidiol gradient, indicating that this Vitamin D metabolite may be more important than believed so far...

..The content and distribution of ALA intracellularly and in tissues is difficult to measure, but PpIX content, on a relative scale, can be easily measured by fluorimetric assays...

..Our results show that singlet oxygen is likely to be the main intermediate in the photodegradation of 5MTHF mediated by Uro. Our findings may be useful for further studies the evolution of human skin colours...

..Photodynamic therapy (PDT) induces physiological changes in human skin, but details and kinetics are not known...

..Our work shows that solutions should be prepared immediately before use and stored at low temperatures. The pH of stock solutions should not exceed 5...

..The presence of cutaneous PpIX together with ambient light may comprise a photosensitizing mechanism by which PpIX may be a photomessenger between ambient light and internal rhythms...

..However, experiments performed in heavy water indicate that generation of singlet oxygen is probably not the explanation for the photosensitizing of folic acid...

..Temperature studies of the formation kinetics of the UV absorbing product also indicate that a complex formation process is involved...

..In conclusion, the present study describes a novel approach of using iron chelating agents without 5-aminolevulinic acid (ALA) to photosensitize cancer cells...

..Since the discovery of oxygen by Joseph Priestley in 1775 it has been recognized that oxygen can be both beneficial and harmful to life...

..Some signal transduction processes are suggested to be involved in ALA-PDT-induced changes in cytoskeleton, cell shape, and adhesion...

..Topical application of ALA-Me followed by exposure with laser light (633nm) delayed the growth of the tumors slightly. Light alone also had a significant effect on the tumor growth...

..The results might provide an explanation of the pH dependency of the cellular uptake of MC 540 observed in this study...

..To investigate whether prognosis of breast-, colon- and prostate cancer may be related to vitamin D(3), induced from solar ultra-violet (UV) radiation, through studies on geographical and seasonal variations in UV radiation...

..In conclusion, the present spectroscopic results show that AlPcS(4) does not form aggregates and is a very stable compound in aqueous solutions...

..99 +/- 0.04 after the application of a model taking aggregation of the drug into account. The contributions of various aqueous ionic species of mTHPP as functions of pH were calculated and compared with partition coefficients...

..In conclusion, application of the 160 mg/g cream for 3 hours gave advantageous porphyrin distributions for all types of lesions...

..The rate of elimination of PpIX from the volume of detection was faster after 420 nm light irradiation than that after 632 nm. These findings are discussed in view of penetration depths of light and ALA-Me, and diffusion of PpIX...

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..Populations living at high latitudes would probably benefit from moderately increasing their exposure to UVB to provide a good vitamin D status...

..The oxygen dependence of FA photodegradation and the inhibition of this process by sodium azide indicate that singlet oxygen may participate in the photosensitizing activity of FA photoproducts...

..These are all important parameters for optimally effective PDT. The present review will give a brief, physically based, overview of PDT and then discuss some of the main biophysical aspects of this therapeutic modality...

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..Within eight weeks after the last exposure the 25(OH)D(3) level decreased to the initial value in all volunteers irrespective of vitamin D supplementation or not...

..Recently, overweight and obesity have been shown to be related to low vitamin D status...

..Thus, a dark skin colour may be favourable for prevention of folate degradation under high solar fluence rates, such as in equatorial areas...

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..This study suggests that 5MTHF in blood can be photodegraded in the presence of the flavins and porphyrins, but protected by bilirubins. This may have health and evolutionary implications...

..Furthermore, there seems to be a correlation between the levels of the two vitamin D metabolites, indicating that the regulation of 1,25(OH)2 vitamin D is not always tight, notably in persons with high BMI...

..A general model for PDT-induced tumor destruction is suggested...

..The potency of 6,4,4'-trimethylangelicin, which does not form DNA interstrand crosslinks, may be related to its high DNA binding constant. Our data may be useful in the selection of compounds to treat vitiligo...

..16 +/- 0.03 mm(2) h(-1)), MAL (0.045 +/- 0.005 mm(2) h(-1)) and HAL (0.037 +/- 0.003 mm(2) h(-1)), the behavior of the drugs after different application times could be estimated in this tumor model...

..The leveling off of melanoma trend is probably associated with melanoma prevention campaigns and with increasing awareness, although vitamin D could play a role...

..Future aspects of applications of photosensitisation of red blood cells are discussed...

..Therefore, in the present historical review, the early work is weighted more heavily than recent work that is more easily accessible to the readers...

..Further studies, using proper, adequate 5-methyltetrahydrofolate methodology, are needed to clarify the influence of broadband phototherapy on folate degradation and the consequences of these on the health of psoriasis patients...

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..5MTHF mainly absorbs, and is degraded by, UVB and UVC, radiation that does not penetrate the earth's atmosphere and the human skin well...

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..In conclusion, the highest tumour to normal skin PpIX ratio was observed 3 h after application of 8% ALA-Me, suggesting that light exposure should be performed at this time in order to achieve an optimal PDT effect in this tumour model...