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At least 163 records · Page 9Linked to original sources
PubMed2000

Ultraviolet B radiation exerts enhancing effects on the production of a complement component, C3, by interferon-gamma-stimulated cultured human epidermal keratinocytes, in contrast to photochemotherapy and ultraviolet A radiation that show suppressive effects.

The present study was designed to investigate by using enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain reaction methods whether photochemotherapy (PUVA) or ultraviolet (UV) B treatment affects C3 production by interferon (IFN)-gamma-stimulated keratinocytes cultured in serum-free medium. The results showed that PUVA and UVA reduced C3 production by IFN-gamma-stimulated epidermal keratinocytes dose-dependently, although the effect of PUVA was stronger than that of UVA alone. Interestingly, UVB induced an enhancement of C3 production at doses ranging from 10 to 50 mJ cm-2. This phenomenon was found at both the protein and mRNA levels. In every experiment, changes in C3 mRNA levels preceded those in its protein levels. Reduced C3 production at higher doses of 75 and 100 mJ cm-2 were probably due to cytotoxic effects of UVB. In our experimental system, PUVA, UVA or UVB treatment did not affect C3 production without IFN-gamma stimulation. Our results suggest that a reduction in C3 production by PUVA treatment may in part explain the efficacy of PUVA in the treatment of inflammatory dermatoses such as psoriasis, while the results of the UVB experiments may partially explain the proinflammatory nature of UVB.

Cells, Cultured↗
PubMed2003

Mechanisms of phototherapy and photochemotherapy for photodermatoses.

Most photodermatoses represent indications for preventive ultraviolet (UV) phototherapy and/or psoralen plus ultraviolet A (PUVA) photochemotherapy. The aim of treatment is to prevent the outbreak of disease by increasing the patient's tolerance to sunlight. The mechanisms by which ultraviolet B (UVB) and PUVA induce such tolerance are not completely understood. Pigmentation and skin thickening may be important factors in the protective effect, but they cannot sufficiently explain the degree of protection induced. Other mechanisms that may be of critical importance for the therapeutic efficacy encompass a variety of immunomodulatory effects on human skin known to be induced by UVA, UVB, and PUVA. Obviously the mechanisms of prophylactic phototherapy are strongly intertwined with the pathogenesis of the photodermatoses. The possible mechanisms of photoprevention are discussed for polymorphic light eruption (PMLE), actinic prurigo, chronic actinic dermatitis, and solar urticaria.

Chronic Disease↗
PubMed2001

Expression of apoptosis markers on peripheral blood lymphocytes from patients with cutaneous T-cell lymphoma during extracorporeal photochemotherapy.

The mechanisms of extracorporeal photochemotherapy (ExP) therapeutic activity in cutaneous T-cell lymphomas (CTCLs) are not yet well understood, even though it has been suggested that a major mechanism may be induction of apoptosis. In vitro studies demonstrate that UVA-induced apoptosis is mediated by CD95-Fas expression and inhibited by Bcl-2 up-regulation and that UVA irradiation is able to down-regulate Bcl-2 expression. High-resolution multiparameter flow-cytometric analyses were used to evaluate Bcl-2/CD95-Fas expression on phenotypically identifiable circulating clonal T cells from 7 patients with CTCL (4 with Sézary syndrome and 3 with mycosis fungoides with peripheral involvement) before and during ExP, in an attempt to ascertain whether Bcl-2/CD95-Fas status can be related to the hematologic response. A Bcl-2 normal phenotype before ExP or a normalization in Bcl-2 expression during ExP were related to a better clinical response, whereas a persistent Bcl-2 high expression was a negative prognostic factor. On the other hand, no response was found in patients with a CD95-Fas-negative phenotype, whereas the expression of CD95-Fas was associated with hematologic remission. Although further studies are needed to confirm these preliminary results, this study suggests that Bcl-2 and CD95-Fas expression could be evaluated, together with the other known clinical and immunologic factors, as additional parameters related to clinical response in patients with CTCL undergoing ExP.

Adult↗
PubMed2001

Adhesion of MNC to extracellular matrix proteins following in vitro photochemotherapy.

BACKGROUND: Photochemotherapy is a safe and effective treatment for patients with drug-resistant severe GvHD. The technique involves the exposure of MNC to psoralen and UVA light (PUVA). We have investigated the effect of in vitro PUVA on MNC adhesion to extracellular matrix (ECM) proteins. METHODS: MNC were isolated from peripheral blood (PB) and umbilical cord blood (UCB), and treated with PUVA. After labeling by a chemiluminescent probe, MNC were plated on ECM proteins (collagen, fibronectin, vitronectin and laminin) and the number of adherent cells was measured. RESULTS: Untreated MNC from both PB and UCB showed a similar adhesion to the substrates. As a consequence of exposure to PUVA, most of PB samples showed significantly enhanced adhesion to the ECM proteins; on the other hand, UCB-recovered MNC did not significantly modify their adhesion. DISCUSSION: MNC adhesion to ECM components is mediated by integrins, a family of cell membrane receptors; the ligand-binding affinity of certain integrins may be modulated by different stimuli. PUVA treatment of PB-recovered MNC may induce the up-regulation of the ligand-binding affinity of the integrins involved in the adhesion to ECM proteins. The finding of unmodified UCB cell adhesion after PUVA, may be related to the functional immaturity of lymphocytes at birth.

Cell Adhesion↗
PubMed1981

A mathematical model of the biologically effective dose of solar UVA received by patients undergoing oral psoralen photochemotherapy for psoriasis.

A theoretical analysis is presented of the biologically effective dose of the solar long wave ultraviolet radiation (UVA) received by patients who are being treated for psoriasis by oral psoralen photochemotherapy. It is shown that patients treated during the summer months in the UK may well receive a UV dose which is comparable with, or even in excess of, the dose of artificial UVA received in the treatment centre and consequently should be advised about limiting their exposure to sunlight on the treatment days. In the winter months in the UK the UVA intensity in sunlight is such that no unduly restrictive precaution need apply. However, at locations between about 40 degrees N and 40 degrees S, the solar UVA intensity in midwinter is still sufficiently high that unnecessary sunlight exposure on treatment days should be avoided.

Humans↗
PubMed1980

The stratum corneum xerotic from aging and photochemotherapy (PUVA). A study by scanning electron microscopy.

The relationship between the structure and mechanical properties of the xerotic stratum corneum from aging and photochemotherapy were studied by scanning electron microscopy. Two different types or orthokeratosis were found in these xeroses, from which we infer that the type induced by PUVA does not represent accelerated aging. The orderly architectural pattern of the stratum corneum in xerosis induced by PUVA may be related to the microanatomy of the prominent undulations at the junction between the epidermis and the papillary dermis.

Adult↗
PubMed1978

Photochemotherapy: dermatologic uses.

Photochemotherapy is a new concept in treating selected skin disease. Psoralens taken orally two hours before high-intensity UVA radiation results in clinical clearing of psoriasis, mycosis fungoides, vitiligo, and atopic eczema. The results of two large cooperative studies in the treatment of psoriasis presented similar results.

Eczema↗
PubMed1996

Monitoring of 8-methoxypsoralen during extracorporeal photochemotherapy: evidence for a "first-dose" effect.

Therapeutic monitoring of 8-methoxypsoralen (8-MOP) was studied in 12 patients (age range 43-85 years, weight range 48-76 kg) treated for Sezary's syndrome by extracorporeal photochemotherapy (ECP) for 14-41 months. Before the beginning of each ECP cycle (2 sessions on consecutive days at about 4-week intervals), a blood sample was drawn to determine the 8-MOP plasma concentration 2 h after drug ingestion. Plasma 8-MOP levels were measured using a high-performance liquid chromatography method with spectrophotometric detection. Monitoring parameters (dose, 2-h plasma 8-MOP concentration) showed important interindividual and intraindividual variations. The 8-MOP dose ranged from 0.57 to 1.04 mg/kg. Intraindividual variations of 2-h 8-MOP levels ranged from 21% to 75%. Of the 652 measurements, 13% were < 100 ng/ml, the therapeutic threshold for effective ECP; in three of the seven patients, increasing the dose obtained levels exceeding the therapeutic threshold, i.e, the absorption was not saturable. Orthogonal regression analysis between plasma 8-MOP concentrations measured in two consecutive ECP sessions showed a first-dose effect: the 2-h plasma 8-MOP concentration was significantly lower after the first administration than after the second (approximately 1.26-fold). Because 8-MOP has been proven to be a potent suicide inhibitor of drug metabolism in rats and humans, it is possible that 8-MOP had an inhibitory effect on its own metabolism within the therapeutic dose range for ECP, which would explain in part the inter- and intraindividual variability in 8-MOP kinetics and first-dose effect.

Adult↗
PubMed1984

Relation of antipsoriatic and Langerhans cell depleting effects of systemic psoralen photochemotherapy: a clinical, enzyme histochemical, and electron microscopic study.

The possible relation between the therapeutic action and Langerhans cell (LC) depleting effect of psoralen photochemotherapy (PUVA) was investigated in 9 psoriatic patients by parallel recording of the clinical status, using the psoriasis area and severity index ( PASI ), and the epidermal LC counts of uninvolved skin, using light (ATPase staining) and electron microscopy (EM). Both light and electron microscopically recorded LC numbers decreased significantly during the PUVA course of, on the average, 21 exposures and a mean cumulative UVA dose of 77 J/cm2. At the end of the treatment period, both the PASI score and the light microscopically recorded LC density had reduced to about one-tenth of original, i.e., from 7.5 +/- 5.7 to 0.8 +/- 0.8 points and from 787 +/- 70 to 60 +/- 48 cells/mm2, respectively. After cessation of the PUVA course, the PASI scores remained low during the 3-7 week follow-up period, while the LC counts returned to normal, and even exceeded the starting value by 12%. Although a possible functional impairment of LC in the post-PUVA period cannot be excluded, the data are interpreted as speaking against the hypothesis that the therapeutic action of PUVA would be mediated through its LC effects.

Adenosine Triphosphatases↗
PubMed1981

The effect of photochemotherapy (PUVA) on cell mediated immunity in the guinea pig.

Guinea pigs were injected intraperitoneally with 8-methoxypsoralen (8-MOP) and afterwards the shaved right flank was irradiated with UV-A. This treatment was performed daily for 14 days. Seven days after treatment started they were immunized with ovalbumin in Freund's complete adjuvant and 7 days later skin tested with ovalbumin on the unirradiated left flank. Photochemotherapy (8-MOP plus UV-A) did not alter the total white blood cells or the proportion of lymphocytes or granulocytes. However, this treatment significantly depressed the delayed hypersensitivity reaction to ovalbumin; nonspecific inflammation, induced by intradermal turpentine, was not altered. In addition, treatment with 8-MOP alone suppressed the skin reaction to ovalbumin, but not to the same extent as treatment with 8-MOP and UV-A. 8-MOP plus UV-A had no effect on macrophage migration inhibition factor but it did significantly depress mitogen and antigen specific lymphocyte transformation.

Animals↗
PubMed1979

Normal T-lymphocyte function in psoriatic patients undergoing methoxsalen photochemotherapy.

Peripheral blood lymphocytes from psoriatic patients undergoing photochemotherapy using oral 8-methoxypsoralen and high-intensity long-wave ultraviolet radiation, were isolated and their ability to respond to phytohemagglutinin and to form spontaneous rosettes with sheep red blood cells was measured in vitro. Seventeen patients were investigated who had received 200 to 3700 Joules/cm2 of ultraviolet radiation over a 6- to 33-month period. No significant defects in lymphocyte blastogenesis or E-rosette formation were detected in these patients.

Adult↗
PubMed1980

Photochemotherapy of psoriasis: DNA damage in blood lymphocytes.

DNA synthesis assessed by 3H thymidine incorporation was measured in lymphocytes from patients with psoriasis receiving photochemotherapy with 8-methoxypsoralen (8-MOP) and UV-A (PUVA). The emission from the UVA source contained sufficient short wavelengths (UV-B) to impair 3H-thymidine incorporation but could be screened out with clear plastic screens. When lymphocytes were irradiated in vitro in a 1/10 dilution of plasma containing 8-MOP, increasing doses of UV-A produced progressive inhibition of phytohaemagglutinin (PHA)-induced DNA synthesis. Cells from patients given several previous treatments were inhibited significantly more than those from patients receiving their first exposure. This was also true for unirradiated cells sugesting either an accumulation of 8-MOP within cells, persistence of DNA damage or alteration of the lymphocyte population. Lymphocytes removed immediately after patients were irradiated showed less 3H thymidine incorporation than cells taken just prior to irradiation, which confirms that PUVA treatment exerts in vivo effects on circulating lymphocytes.

DNA↗
PubMed1977

Problems associated with ultraviolet dosimetry in the photochemotherapy of psoriasis.

A hypothetical action spectrum for the regression of lesions in photochemotherapy of psoriasis is proposed. An ideal detector should have a wavelength response which matches this action spectrum but this is generally not the case with commercially available photometers. The problems that may arise by indiscriminate use of such detectors are discussed, together with a suggested solution.

Humans↗
PubMed1977

Photochemotherapy for pustular psoriasis (von Zumbusch).

Photochemotherapy (PUVA) with oral methoxsalen and UV-A was instituted in 8 patients with generalized pustular psoriasis (von Zumbusch). Complete clearing of skin lesions and of systemic symptoms was achieved in all patients. Patients who had been on systemic treatment prior to PUVA had to be treated with considerably more UV-A energy than patients who had received topical therapy alone. Seven patients were kept in complete remission by maintenance therapy for an observation period of up to 1 1/2 years. Side effects of systemic pre-PUVA treatment resolved during several months of maintenance therapy.

Adolescent↗
PubMed1979

5-Methoxypsoralen (Bergapten) in photochemotherapy of psoriasis.

5-Methoxypsoralen (5-MOP, Bergapten) was evaluated as a potential photosensitizing drug in oral photochemotherapy of psoriasis. Treatment results indicate that (1) 5-MOP is as effective as, and in high doses more effective than, 8-methoxypsoralen in clearing psoriatic lesions; (2) therapeutic doses of 5-MOP do not lead to erythema; the acute side-effects of 8-MOP PUVA therapy--erythema, blistering, pruritus--are thus avoided; (3) even high doses of 5-MOP are not followed by nausea. 5-MOP PUVA therapy thus represents a real alternative to 8-MOP PUVA, its advantages over 8-MOP PUVA being greater safety and patient acceptance.

Drug Administration Schedule↗
PubMed1979

Photochemotherapy (PUVA) of psoriasis using 3-carbethoxypsoralen, a non-carcinogenic compound in mice.

The carcinogenic risk of photochemotherapy (PUVA) with bi-functional furocoumarins such as 8-methoxypsoralen (8-MOP) which form cross-links in cellular DNA has initiated a search for active but less hazardous psoralens. A new compound, 3-carbethoxypsoralen (3-CPs), studied in the yeast Saccharomyces cerevisiae (eukaryote), has been shown to be very photoactive on DNA and to form only mono-additions to DNA. These lesions appear to be more easily repaired than the cross-links induced by 8-MOP. 3-CPs produces less nuclear genetic events such as nuclear mutations and mitotic crossovers, but more cytoplasmic 'petite' mutations (damage to mitochondrial DNA) than 8-MOP. In mice it was demonstrated that after local or intra-peritoneal administration, in contrast to 8-MOP, 3-CPs is non-toxic, non-erythematogenic, and non-carcinogenic. A study of ten psoriatic patients had shown that local applications of 3-CPs plus UV-A exhibit about the same therapeutic activity for the clearing of psoriatic lesions as local treatment with 8-MOP plus UV-A, but without any localized hyperpigmentation.

Animals↗
PubMed1980

A survey of the ultraviolet radiation emissions of photochemotherapy units.

Measurements have been made of the spectral emission and irradiance from whole body ultraviolet irradiation units used in the treatment of psoriasis by photochemotherapy (PUVA). A total of ten units were studied, located at nine different treatment centres in England. The results showed that within the limits of experimental accuracy there was no significant difference in the profile of all spectra measured, although the measured value of irradiance compared with each centre's own UV-A meter showed wide discrepancies. There is poor documentation provided by manufacturers of UV-A meters on the meaning of the scale reading in mWcm-2, and it would seem expedient that some agreed calibration procedure for these instruments is forthcoming.

England↗