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At least 343 records · Page 19Linked to original sources
PubMed1996

Apoptosis induction of ultraviolet light A and photochemotherapy in cutaneous T-cell Lymphoma: relevance to mechanism of therapeutic action.

The anti-tumor action of many chemotherapeutic agents has recently been attributed to the induction of apoptosis in the malignant cell population. In this study, we investigated the ability of extracorporeal photopheresis (ExP) and in vitro PUVA (8-methoxy-psoralen + ultraviolet A) therapy to induce apoptosis in peripheral blood mononuclear cells from Sezary syndrome patients and normal controls. Flow cytometric analysis of ExP- or PUVA-treated peripheral blood lymphocytes demonstrated two distinct cell populations within 24 h of treatment. One population was similar to untreated controls with the other exhibiting characteristics of apoptotic cell death, i.e., a loss of cell volume and an accompanying increase in cell density. This latter population was comprised of cells with DNA strand breaks as determined by the Tdt-mediated deoxyuridine triphosphate-biotin nick end labeling assay. Apoptosis was also confirmed morphologically by fluorescent and electron microscopy as well as by demonstration of characteristic DNA strand breaks (laddering) using gel electrophoresis. Apoptosis was not observed with 8-methoxypsoralen (< or = 300 ng per ml) alone; however, ultraviolet A alone at doses > or = 2 J per cm2 induced apoptosis in lymphocytes. Peripheral blood T-cell subpopulations of Sezary syndrome patients, including the malignant clone, were equally susceptible to apoptosis subsequent to either photopheresis or PUVA treatment. In contrast, monocytes (CD14+/CD45+) appear to be resistant to apoptosis induction by ExP or PUVA treatment. Moreover, ExP-treated and untreated monocytes phagocytized apoptotic, but not untreated, peripheral blood mononuclear cells. ExP and PUVA have been shown to be efficacious and well-tolerated therapies in the treatment of dermatologic diseases and transplant rejection. These data suggest that induction of apoptosis may be an important event for therapeutic efficacy.

Apoptosis↗
PubMed1977

The effects of indomethacin on long-wave ultraviolet-induced delayed erythema.

Indomethacin, a known inhibitor of prostaglandin synthesis, administered topically as a 2.5% solution, intradermally in 10 mug doses, and orally in a dose of 150 mg/day for 2 days did not diminish the delayed erythema produced a long-wave ultraviolet light (320-400 nm). The delayed phototoxic erythema produced by 8-methoxypsoralen and subsequent exposure the long-wave ultraviolet light was similarly unaffected. By comparison, topical and intradermal indomethacin treatment produced sustained decrease in the erythemal response to ultraviolet radiation in the UVB ranges (290-320 nm).

Administration, Oral↗
PubMed1977

Decreased thymidine incorporation in circulating leukocytes after treatment of psoriasis with psoralen and long-wave ultraviolet light.

Tritiated thymidine incorporation, a measure of DNA synthesis, was studied in circulating leukocytes from patients with widespread psoriasis who were being treated with photochemotherapy using oral 8-methoxypsoralen (8-MOP) and high-intensity, long-wave ultraviolet light (UVA). Seven of 13 psoriasis patients treated with photochemotherapy demonstrated a significant (p less than 0.05) reduction in leukocyte incorporation of tritiated thymidine immediately after UVA in comparison to incorporation before UVA. None of 10 control subjects treated with UVA alone demonstrated such reduction in leukocyte tritiated thymidine incorporation. Photochemotherapy thus affects circulating blood cells in some patients with psoriasis in addition to its therapeutic effect on epidermal cells. Further investigations are needed to determine the reasons for the differences in susceptibility to inhibition of leukocyte DNA synthesis among patients and the possible long-term consequences of such inhibition.

Coumarins↗
PubMed1979

The effects of psoralen and UVA (PUVA) on epidermal melanocytes of the tail in C57BL mice.

The morphological and numerical changes in epidermal melanocytes in tail skin of C57BL mice after exposure to psoralen followed by UVA irradiation were studied. The dorsal aspect of the tail was painted daily for 5 days a week with 0.1 ml methoxsalen (8-methoxypsoralen) in acetone, followed by UVA irradiation (peak 365 nm) after 2 hr with increasing energies up to a maximum of 2.0 J/cm2 daily. Control animals received UVA or acetone treatment only. The total duration of the experiment was 8 weeks. Biopsies taken after 1 and 3 days, 1, 2, 4, 6 and 8 weeks were studied by the combined skin-splitting DOPA techniques. After 2 weeks of PUVA treatment the original brick like arrangement of melanocytes was obliterated and replaced by a confluent layer of melanocytes, and after 4 weeks the number of melanocytes had tipled and these cells also appeared on the epithelium covering the pilosebaceous units. UVA treatment alone did not show these effects. Inflammation and denuding of the skin after 4 weeks was followed by regeneration of the epidermis and the melanocyte system, in spite of continuing PUVA treatment.

Acetone↗
PubMed1976

Cutaneous effects of pulsed nitrogen gas laser irradiation.

The effects of pulsed nitrogen gas laser emission (337.1 nm wavelength) were studied on human skin. The laser provides high-intensity monochromatic UVA radiation and can elicit delayed erythema in an actual exposure time of about 1 msec (105,000 pulses, each lasting 10 nsec, delivered over 210 sec). The effects of nitrogen laser irradiation were compared clinically and histologically with conventional erythemogenic UVA and UVB exposures from xenon arc or mercury arc lamps and were found to be similar in many respects. The minimal erythema dose is comparable to that obtained using more conventional continuous light sources which have more than 100 times lower intensity. A phototoxicity comparison of oral and topically applied psoralens is presented, indicating that the laser may prove useful in comparing photosenitizing capacity of certain compounds.

Animals↗
PubMed1979

New studies on the interaction between 8-methoxypsoralen and DNA in vitro.

Some aspects of the interactions between DNA and 8-methoxypsoralen (8-MOP) in its ground state (complex formation) or in its excited state (photobinding) have been investigated. 8-MOP shows a low affinity towards DNA in the complex formation; this fact minimizes the possible biological consequences deriving from this interaction, when it occurs in vivo. In covalent photobinding to DNA, 8-MOP forms mainly monofunctional adducts, and to a lesser extent bifunctional adducts, showing a behavior similar to that of other linearly condensed furocoumarins (psoralens); the ratio between mono- and bifunctional adducts was found to be 9:1. The covalent photobinding to DNA does not occur at random along the macromolecule, but preferentially at the level of specific receptor sites. The regions having an alternate sequence of A-T seem to be the best receptor sites for the formation of monoadducts while the regions containing an alternate sequence of A-T and C-G appeared to be the preferential sites for the cross-linkage formation.

Base Sequence↗
PubMed1990

Ultrastructural modification of the plasma membrane in HUT 102 lymphoblasts by long-wave ultraviolet light, psoralen, and PUVA.

Ultrastructural alterations of the plasma membrane in HUT 102 lymphoblasts were assessed after a 2-h interaction with a suprapharmacologic (15 micrograms/ml) concentration of 8-MOP, 2-h irradiation with UVA (2.1 mW/cm2), and the exposure of the HUT 102 cells to PUVA under the same conditions. The dark reaction of HUT cells with 8-MOP resulted in the disappearance of microvilli, the emergence of plasma-membrane-associated spherical bodies, formation of lamellar fungiform membrane evaginations, and, in approximately 1% of the cells, formation of uropods and cell capping. Except for uropod formation and cell capping, UVA has induced the same plasma-membrane alterations, and was more deleterious to structural cytoplasmic integrity than 8-MOP. Morphologic changes of the plasma membrane in PUVA-exposed cells tended to replicate structural alterations elicited independently during the dark reaction by suprapharmacologic 8-MOP concentrations. Partial retention of microvilli by cells after PUVA was the sole exception. In light of all available evidence we conclude that psoralen during the dark reactions interacts with plasma membrane lipids by as yet undisclosed mechanisms and that in addition to lipids, membrane proteins are also the primary target of the initial interaction of HUT 102 cells with psoralen during PUVA treatment.

Cell Membrane↗
PubMed1975

A comparative clinical evaluation of trimethylpsoralen, psoralen and 8-methoxypsoralen in treating vitiligo.

Trimethylpsoralen, psoralen and 8-methoxypsoralen were adminstered in 10 mg dosage orally to 37, 29 and 23 patients with vitiligo. Complete improvement was noted in 8.9% and partial improvement was recorded in 59.5%. The overall results produced by trimethylpsoralen and psoralen were superior to those of 8-methoxypsoralen. There was no significant therapeutic difference noticed in regards to age, sex, duration and type of vitiligo.

Coumarins↗
PubMed2005

Bivalent effect of UV light on human skin mast cells-low-level mediator release at baseline but potent suppression upon mast cell triggering.

Ultraviolet (UV) irradiation is an established treatment for inflammatory skin diseases, although the precise mode of action is still unclear. Activating and suppressive effects on mast cell (MC) mediator release have been described. The aim of this study was to investigate systematically the effects of UVB, UVA-1, and psoralen plus UVA-1 at therapeutic doses on skin-derived human MC. Baseline and stimulated release of histamine, tryptase, and of interleukin (IL)-6, IL-8 and tumor necrosis factor-alpha (TNF-alpha) were examined. In resting MC, UV light induced a slight, yet significant histamine release corresponding to enhanced surface levels of lysosome-associated membrane proteins (LAMP). In contrast, UV pre-treatment caused a marked suppression of the anti-IgE-induced histamine release, accompanied by a diminished, anti-IgE-mediated increase in LAMP expression. The secretion of IL-6, IL-8, and TNF-alpha was inhibited in resting and activated MC, suggesting a different mode of action. Regarding the importance of MC in a variety of allergic and inflammatory processes, our data show a high susceptibility of this cell type towards UV light, which seems to partially depend on the state of cellular activation. Immunosuppressive effects predominate in activated MC, thus corresponding with the beneficial effects in inflammatory diseases, whereas in resting MC, both stimulatory and inhibitory effects are observed.

Cytokines↗
PubMed2005

High levels of ultraviolet B exposure increase the risk of non-melanoma skin cancer in psoralen and ultraviolet A-treated patients.

Sunlight and psoralen and ultraviolet A (PUVA) are risk factors for the development of squamous cell carcinoma (SCC) and, to a lesser extent, basal cell carcinoma (BCC). Ultraviolet B (UVB) therapy, used for the treatment of psoriasis, might also increase the risk of these tumors. We studied the relation of skin cancer incidence to UVB use among 1380 adult subjects enrolled in a long-term safety trial of PUVA therapy. We used negative binomial regression models to quantify the association between UVB and the development of non-melanoma skin cancer (NMSC), controlling for known confounders. High UVB exposure (> or =300 treatments vs <300 treatments) was associated with a modest but significant increase in SCC (adjusted incidence rate ratio (IRR)=1.37, 95% confidence interval (CI)=1.03-1.83) and BCC (adjusted IRR=1.45, 95% CI=1.07-1.96) risk. Among patients with <100 PUVA treatments, high UVB exposure was significantly associated with the development of SCC (adjusted IRR=2.75, 95% CI=1.11-6.84) and BCC (adjusted IRR=3.00, 95% CI=1.30-6.91) on body sites typically exposed to UVB therapy but not on chronically sun-exposed sites typically covered during therapy. For adults with high UVB exposure levels, UVB confers a modest increase in NMSC risk, much less than that observed with PUVA. Therefore, UVB remains a relatively low-risk treatment for psoriasis.

Adult↗
PubMed1996

Modified Thiersch grafting in stable vitiligo.

Medical management of vitiligo usually gives complete repigmentation in up to 60 to 90% of cases (4, 7). Modified Thiersh grafting, in which psoralen without UVA or solar radiation was used successfully, is described.

Adolescent↗
PubMed2003

Treatment of persistent severe atopic dermatitis in 113 Japanese patients with oral psoralen photo-chemotherapy.

Oral administration of psoralen and whole body exposure to UVA (oral PUVA) has been used for the treatment of 113 patients with severe atopic dermatitis (AD). 8-Methoxypsoralen (8-MOP) was given at a dose of 0.5-0.6 mg/kg two hours prior to UVA (3-8 J/cm2) irradiation. Patients were treated three times a week while hospitalized. Other medications which had been given before PUVA therapy were permitted. At four and eight weeks after PUVA therapy, the severity score of AD had decreased by 51% and 80%, and the cumulative doses of UVA were 51.2 J/cm2 and 115.3 J/cm2, respectively. The amounts and strength of topical cortico-steroids were decreased during PUVA therapy. No adverse effects that required discontinuation of the PUVA therapy were observed. After discharge, maintenance therapy with UVB phototherapy and/or conventional treatment of AD kept the patients in remission in the outpatient clinic. The QOL of patients was greatly improved. Photochemotherapy with oral 8-MOP can be indicated in patients with severe, widespread AD, especially if standard therapy fails. This is the first report of oral PUVA therapy in a large series of Japanese patients with AD.

Administration, Oral↗
PubMed2006

Formation of 8-hydroxy-2'-deoxyguanosine in the DNA of cultured human keratinocytes by clinically used doses of narrowband and broadband ultraviolet B and psoralen plus ultraviolet A.

Psoralen plus ultraviolet A (PUVA) and narrowband ultraviolet B (UVB) are widely used in skin disease phototherapy. Recently, the efficacy of UVB therapy has been greatly improved by narrowband UVB, compared to conventional broadband UVB. The objectives of the current study were to evaluate the influence of UVB-induced and PUVA-induced oxidative stress on cultured keratinocytes. We analyzed 8-hydroxy-2'-deoxyguanosine (8-OH-dG) in human keratinocytes (HaCaT cell line) using a high-performance liquid chromatography system equipped with an electrochemical detector. Non-irradiated human keratinocytes contained a baseline of 1.48 +/- 0.22 (mean +/- SD) 8-OH-dG per 10(6) deoxyguanosine (dG) residues in cellular DNA, which increased linearly with higher doses of UVB. When their abilities to induce 8-OH-dG were compared to each other, based on the minimal erythemal and therapeutically used doses, by irradiating them with broadband UVB at 100 mJ/cm(2), the amount of 8-OH-dG increased to 3.42 +/- 0.46 residues per 10(6) dG, while a narrowband UVB treatment at 1000 mJ/cm(2), with biological effects comparable to those elicited by 100 mJ/cm(2) broadband UVB, increased it to 2.06 +/- 0.31 residues per 10(6) dG. PUVA treatment, with 100 ng/mL 8-methoxypsoralen and 5000 mJ/cm(2) UVA, increased the 8-OH-dG level to 4.52 +/- 0.42 residues per 10(6) dG. When HaCaT cells treated with 2000 mJ/cm(2) narrowband UVB were cultured and the amount of 8-OH-dG was monitored in the living cells, 65.6% of the residues were repaired 24 h after treatment. Our study provides a warning that widely used narrowband UVB and PUVA induce cellular oxidative DNA damage at the therapeutically used doses, although to a lesser degree than broadband UVB with the same clinically effective dose.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1977

A study of oil of bergamot and its importance as a phototoxic agent. I. Characterization and quantification of the photoactive component.

It is important in the technique of photopatch testing, using oil of bergamot, to have determined the concentration of the active psoralen, bergapten, so as to avoid false negative responses in the assessment of phototoxic reactions. Techniques for assessing the phototoxic components of oil of bergamot are described and quantitative analyses of bergapten, the only significant photoactive compound in the samples examined, are reported. The phototoxicity of bergapten was found to be nearly the same as that of xanthotoxin (8-MOP) in tests on human skin.

Coumarins↗
PubMed1978

Induction of mixed-function oxidases in mouse liver by psoralens.

8-methoxypsoralen, the most widely used psoralen in photochemotherapy, was shown to induce mixed-function oxidases. Induction of mixed-function oxidases in mouse liver was examined after mice were given a single dose of one of three psoralens. 8-methoxypsoralen clearly induced p-nitroanisole O-demethylase and slightly induced aryl hydrocarbon hydroxylase. Psoralen and 4,5',8-trimethylpsoralen failed to induce either enzyme. These results represent the first enzyme induction studies on these clinically useful compounds. The studies may have relevance in understanding the clinical differences in skin photosensitizing activity and photochemotherapeutic effectiveness of the compounds in such diseases as psoriasis and vitiligo.

Administration, Oral↗
PubMed1978

PUVA appraisal.

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Animals↗