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1.
Eur J Neurosci ; 58(7): 3605-3617, 2023 10.
Article in English | MEDLINE | ID: mdl-37671643

ABSTRACT

Xanthotoxin (XAT) is a natural furanocoumarin clinically used in the treatment of skin diseases such as vitiligo and psoriasis. Recent studies have also investigated its effects on anti-inflammatory, anti-cognitive dysfunction, and anti-amnesia as a guideline for clinic application. However, little is known about its effects on pain relief. Here, we tested the analgesic effects of XAT in serious acute pain and chronic pain models. For acute pain, we used hot-, capsaicin- and formalin-induced paw licking. Nociceptive threshold was measured by mechanical stimuli with von Frey filaments. For chronic pain, we injected complete Freund's adjuvant (CFA) into the mice's plantar surface of the hind paw to induce inflammatory pain. Heat and mechanical hyperalgesia were evaluated by radiant heat and von Frey filament tests, respectively. To investigate the mechanisms underlying the analgesic effect of XAT, we used calcium imaging and western blot to assess transient receptor potential vanilloid 1 (TRPV1) activity and expression in isolated L4-L6 dorsal root ganglion (DRG) neurons. Haematoxylin and eosin (HE) staining, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) were used to examine immune cell recruitment and proinflammatory factor release from skin tissue from paw injection sites. Our results demonstrated that XAT not only reduced acute pain behaviors generated by hot, capsaicin, and formalin but also attenuated CFA-induced heat and mechanical hyperalgesia. The analgesic activity of XAT may be achieved by controlling peripheral inflammation, lowering immune cell infiltration at the site of inflammatory tissue, reducing inflammatory factor production, and therefore inhibiting TRPV1 channel sensitization and expression.


Subject(s)
Acute Pain , Chronic Pain , Mice , Animals , Hyperalgesia/metabolism , Methoxsalen/adverse effects , Capsaicin/pharmacology , Analgesics/pharmacology , Analgesics/therapeutic use , Anti-Inflammatory Agents/adverse effects , Inflammation/metabolism , Formaldehyde/adverse effects , Ganglia, Spinal/metabolism
3.
Oxid Med Cell Longev ; 2022: 8615242, 2022.
Article in English | MEDLINE | ID: mdl-35509838

ABSTRACT

Bergapten (BP) or 5-methoxypsoralen (5-MOP) is a furocoumarin compound mainly found in bergamot essential oil but also in other citrus essential oils and grapefruit juice. This compound presents antibacterial, anti-inflammatory, hypolipemic, and anticancer effects and is successfully used as a photosensitizing agent. The present review focuses on the research evidence related to the therapeutic properties of bergapten collected in recent years. Many preclinical and in vitro studies have been evidenced the therapeutic action of BP; however, few clinical trials have been carried out to evaluate its efficacy. These clinical trials with BP are mainly focused on patients suffering from skin disorders such as psoriasis or vitiligo. In these trials, the administration of BP (oral or topical) combined with UV irradiation induces relevant lesion clearance rates. In addition, beneficial effects of bergamot extract were also observed in patients with altered serum lipid profiles and in people with nonalcoholic fatty liver. On the contrary, there are no clinical trials that investigate the possible effects on cancer. Although the bioavailability of BP is lower than that of its 8-methoxypsoralen (8-MOP) isomer, it has fewer side effects allowing higher concentrations to be administered. In conclusion, although the use of BP has therapeutic applications on skin disorders as a sensitizing agent and as components of bergamot extract as hypolipemic therapy, more trials are necessary to define the doses and treatment guidelines and its usefulness against other pathologies such as cancer or bacterial infections.


Subject(s)
Methoxsalen , Oils, Volatile , 5-Methoxypsoralen , Humans , Methoxsalen/adverse effects , Photosensitizing Agents , Plant Extracts , Ultraviolet Rays
4.
Photochem Photobiol Sci ; 20(10): 1299-1307, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34559384

ABSTRACT

PUVA is a treatment that combines oral methoxypsoralen (8-MOP) with ultraviolet radiation A (UVA). It is used for severe psoriasis and the early stages of T-cell lymphoma. X-rays are an effective treatment for skin cancers. Both treatments are in higher doses used to treat skin malignancies and simultaneously increase the risk of keratinocyte cancer. The main objective of this study was to test whether a few PUVA or X-ray treatments could delay the development of ultraviolet radiation (UVR)-induced skin tumors in a well-established hairless mouse model. Three groups of immunocompetent mice (total, N = 75) were included in the study. All groups were UVR-exposed during the study period. In addition, one group was treated with PUVA and another group was treated with X-rays at days 45, 52, 90 and 97. A control group was treated with UVR only. We recorded when the first, second and third skin tumors were induced in each mouse. Skin tumors developed significantly earlier in both the PUVA and X-ray groups (median, 188 days) than in the control mice (median, 215 days; p < 0.001). Therefore, a few X-ray and PUVA treatments both significantly accelerated the development of skin tumors in hairless mice, compared to UVR controls. Neither treatment showed a delay of UVR-induced skin tumors and caution should be exercised before applying these treatments to sun-damaged skin.


Subject(s)
Methoxsalen/adverse effects , Skin Neoplasms/etiology , Ultraviolet Rays , Animals , Immunocompromised Host , Kaplan-Meier Estimate , Methoxsalen/chemistry , Methoxsalen/pharmacology , Mice , Mice, Hairless , Neoplasms, Radiation-Induced/etiology , Skin/pathology , Skin Neoplasms/mortality , Skin Neoplasms/pathology , Skin Pigmentation/drug effects , Skin Pigmentation/radiation effects , X-Rays
7.
Regul Toxicol Pharmacol ; 92: 303-314, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29196029

ABSTRACT

The aim of the present work was to evaluate the effects of photo-activated toxicity induced after administration of two known melanin-binding phototoxic compounds, sparfloxacin (SPX) and 8-methoxypsoralen (8-MOP), followed or not by UVA/Vis exposure, in pigmented rats (Long Evans: LE) and albino rats (Sprague Dawley: SD). Groups of three rats were treated with SPX or 8-MOP by oral gavage for six consecutive days. Irradiated animals were submitted to a UVA/Vis light dose standardized to 10 J/cm2 UVA daily. Clinical signs, cutaneous reactions and body weight were monitored throughout the study period. Ear biopsy weight, lymph node weight and lymph node cell count were determined at necropsy. Ophthalmologic examinations were performed before the first treatment and on the day of sacrifice. Microscopic examinations were performed on skin biopsies and eyes. Phototoxicity was demonstrated for both SPX and 8-MOP in the pigmented and albino strains, in terms of auricular irritation, lymph node weight and proliferation index, cutaneous reactions and ocular histopathology. LE rats were less sensitive than SD rats, especially at the ocular level, supporting the notion that pigmentation may provide protection against photo-activation. The pigmented rat may be a more relevant model than the albino rat for human safety evaluation.


Subject(s)
Dermatitis, Phototoxic/etiology , Fluoroquinolones/adverse effects , Methoxsalen/adverse effects , Pigmentation/drug effects , Animals , Cell Proliferation/drug effects , Eye/drug effects , Female , Lymph Nodes/drug effects , Rats , Rats, Long-Evans , Rats, Sprague-Dawley , Skin/drug effects , Ultraviolet Rays/adverse effects
8.
Cochrane Database Syst Rev ; 8: CD012537, 2017 08 02.
Article in English | MEDLINE | ID: mdl-28770976

ABSTRACT

BACKGROUND: Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. While in the past pain was largely dismissed and was frequently left untreated, views on children's pain have changed over time, and relief of pain is now seen as important.We designed a suite of seven reviews on chronic non-cancer pain and cancer pain (looking at antidepressants, antiepileptic drugs, non-steroidal anti-inflammatory drugs, opioids, and paracetamol) in order to review the evidence for children's pain utilising pharmacological interventions.As the leading cause of morbidity in the world today, chronic disease (and its associated pain) is a major health concern. Chronic pain (that is pain lasting three months or longer) can arise in the paediatric population in a variety of pathophysiological classifications (nociceptive, neuropathic, or idiopathic) from genetic conditions, nerve damage pain, chronic musculoskeletal pain, and chronic abdominal pain, as well as for other unknown reasons.Non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat pain, reduce fever, and for their anti-inflammation properties. They are commonly used within paediatric pain management. Non-steroidal anti-inflammatory drugs are currently licensed for use in Western countries, however they are not approved for infants under three months old. The main adverse effects include renal impairment and gastrointestinal issues. Common side effects in children include diarrhoea, headache, nausea, constipation, rash, dizziness, and abdominal pain. OBJECTIVES: To assess the analgesic efficacy and adverse events of NSAIDs used to treat chronic non-cancer pain in children and adolescents aged between birth and 17 years, in any setting. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online, MEDLINE via Ovid, and Embase via Ovid from inception to 6 September 2016. We also searched the reference lists of retrieved studies and reviews, as well as online clinical trial registries. SELECTION CRITERIA: Randomised controlled trials, with or without blinding, of any dose and any route, treating chronic non-cancer pain in children and adolescents, comparing any NSAID with placebo or an active comparator. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for eligibility. We planned to use dichotomous data to calculate risk ratio and number needed to treat for one additional event, using standard methods. We assessed GRADE and created three 'Summary of findings' tables. MAIN RESULTS: We included seven studies with a total of 1074 participants (aged 2 to 18 years) with chronic juvenile polyarthritis or chronic juvenile rheumatoid arthritis. All seven studies compared an NSAID with an active comparator. None of the studies were placebo controlled. No two studies investigated the same type of NSAID compared with another. We were unable to perform a meta-analysis.Risk of bias varied. For randomisation and allocation concealment, one study was low risk and six studies were unclear risk. For blinding of participants and personnel, three studies were low risk and four studies were unclear to high risk. For blinding of outcome assessors, all studies were unclear risk. For attrition, four studies were low risk and three studies were unclear risk. For selective reporting, four studies were low risk, two studies were unclear risk, and one study was high risk. For size, three studies were unclear risk and four studies were high risk. For other potential sources of bias, seven studies were low risk. Primary outcomesThree studies reported participant-reported pain relief of 30% or greater, showing no statistically significant difference in pain scores between meloxicam and naproxen, celecoxib and naproxen, or rofecoxib and naproxen (P > 0.05) (low-quality evidence).One study reported participant-reported pain relief of 50% or greater, showing no statistically significant difference in pain scores between low-dose meloxicam (0.125 mg/kg) and high-dose meloxicam (0.25 mg/kg) when compared to naproxen 10 mg/kg (P > 0.05) (low-quality evidence).One study reported Patient Global Impression of Change, showing 'very much improved' in 85% of ibuprofen and 90% of aspirin participants (low-quality evidence). Secondary outcomesAll seven studies reported adverse events. Participants reporting an adverse event (one or more per person) by drug were: aspirin 85/202; fenoprofen 28/49; ibuprofen 40/45; indomethacin 9/30; ketoprofen 9/30; meloxicam 18/47; naproxen 44/202; and rofecoxib 47/209 (very low-quality evidence).All seven studies reported withdrawals due to adverse events. Participants withdrawn due to an adverse event by drug were: aspirin 16/120; celecoxib 10/159; fenoprofen 0/49; ibuprofen 0/45; indomethacin 0/30; ketoprofen 0/30; meloxicam 10/147; naproxen 17/285; and rofecoxib 3/209 (very low-quality evidence).All seven studies reported serious adverse events. Participants experiencing a serious adverse event by drug were: aspirin 13/120; celecoxib 5/159; fenoprofen 0/79; ketoprofen 0/30; ibuprofen 4/45; indomethacin 0/30; meloxicam 11/147; naproxen 10/285; and rofecoxib 0/209 (very low-quality evidence).There were few or no data for our remaining secondary outcomes: Carer Global Impression of Change; requirement for rescue analgesia; sleep duration and quality; acceptability of treatment; physical functioning as defined by validated scales; and quality of life as defined by validated scales (very low-quality evidence).We rated the overall quality of the evidence (GRADE rating) for our primary and secondary outcomes as very low because there were limited data from studies and no opportunity for a meta-analysis. AUTHORS' CONCLUSIONS: We identified only a small number of studies, with insufficient data for analysis.As we could undertake no meta-analysis, we are unable to comment about efficacy or harm from the use of NSAIDs to treat chronic non-cancer pain in children and adolescents. Similarly, we cannot comment on our remaining secondary outcomes: Carer Global Impression of Change; requirement for rescue analgesia; sleep duration and quality; acceptability of treatment; physical functioning; and quality of life.We know from adult randomised controlled trials that some NSAIDs, such as ibuprofen, naproxen, and aspirin, can be effective in certain chronic pain conditions.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Arthritis, Juvenile/drug therapy , Arthritis, Rheumatoid/drug therapy , Chronic Pain/drug therapy , Adolescent , Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Aspirin/adverse effects , Aspirin/therapeutic use , Celecoxib/adverse effects , Celecoxib/therapeutic use , Child , Child, Preschool , Chronic Disease , Fenoprofen/adverse effects , Fenoprofen/therapeutic use , Humans , Ibuprofen/adverse effects , Ibuprofen/therapeutic use , Lactones/adverse effects , Lactones/therapeutic use , Meloxicam , Methoxsalen/adverse effects , Methoxsalen/therapeutic use , Naproxen/adverse effects , Naproxen/therapeutic use , Randomized Controlled Trials as Topic , Sulfones/adverse effects , Sulfones/therapeutic use , Thiazines/adverse effects , Thiazines/therapeutic use , Thiazoles/adverse effects , Thiazoles/therapeutic use
9.
J Clin Apher ; 32(4): 257-265, 2017 Aug.
Article in English | MEDLINE | ID: mdl-27476149

ABSTRACT

The GvHD is a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Extracorporeal photopheresis (ECP) represents an alternative therapeutic strategy to immunosuppressive therapy. Although ECP is used since 1990s, the mechanism of action has not yet been completely clarified. We analyzed cells collected from 20 ECP procedures of 4 patients affected by chronic GvHD and, for comparison, Peripheral Blood Mononuclear Cells (PBMCs) of 10 healthy donors undergoing from same type of photochemiotherapy, evaluating by flow cytometry, the effects before and after photoactivation with 8-MOP. The analysis showed a significant increase in cell death after ECP in particular in CD4 T lymphocytes as described in literature correlated with haematocrit value. Most interesting data emerge from the analysis of cytotoxic activity of NK cells, using flow cytometry analysis of surface expression of CD107a in the presence of target cells (K562). In all analyzed samples it was possible to document a statistically significant reduction of the cytotoxic activity of NK cells after photoactivation. The decrease of the cytotoxic activity was related to hematocrit value of leukoapheresis: in fact, lower HCT values were associated with a more marked reduction of cytotoxic activity. The study confirms literature data about the increase of cellular mortality induce by ECP. Furthermore, for the first time it is demonstrated that the ECP exerts a marked and significant inhibitory effect on the cytotoxic activity of NK cells. Our study suggests that lower values of hematocrit are associated with better treatment outcome.


Subject(s)
Hematocrit/adverse effects , Immunomodulation , Killer Cells, Natural/drug effects , Photopheresis/methods , Adolescent , Case-Control Studies , Cell Death/drug effects , Child , Female , Flow Cytometry , Humans , K562 Cells , Lysosomal-Associated Membrane Protein 1/analysis , Male , Methoxsalen/adverse effects
10.
Br J Dermatol ; 174(1): 131-5, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26383592

ABSTRACT

BACKGROUND: Published methodology used to determine psoralen plus ultraviolet A (PUVA) erythemal action spectrum does not reflect current clinical practice for psoralen sensitization. We re-evaluated the PUVA action spectrum using aqueous 8-methoxypsoralen (8-MOP) 2·6 mg L(-1) as used routinely in current clinical practice. OBJECTIVES: To determine the UVA erythema action spectrum of topical 8-MOP-sensitized normal skin. METHODS: Twenty healthy volunteers with skin phototypes I-V were recruited. Forearms were psoralen-sensitized at 37 °C for 10 min. Six UVA irradiations at 10-nm intervals between 325 and 375 nm were randomly allocated to forearm sites and were applied using a 10-nm bandwidth irradiation monochromator. The visual minimal phototoxic dose (MPD) was recorded on each site at 96 h. RESULTS: Volunteer Boston phototypes were: I, n = 2; II, n = 6; III, n = 6; IV, n = 5 and V, n = 1. The mean MPD (J cm(-2) ) for all subjects at each wavelength was as follows: 325 nm, 0·64 (SD 0·37); 335 nm, 0·80 (SD 0·58); 345 nm, 0·96 (SD 0·55); 355 nm, 1·50 (SD 0·85); 365 nm, 2·19 (SD 0·90); and 375 nm, 2·89 (SD 1·06). Therefore, the relative sensitization at each wavelength (erythemal action spectrum) was: 1, 0·83, 0·67, 0·43, 0·29 and 0·22. There were significant differences between the PUVA erythemal effectiveness at different wavelengths but none between skin types. CONCLUSIONS: This study has established the erythemal action spectrum for bath/soak PUVA therapy as is currently performed. In all volunteers, the peak sensitivity was at 325 nm. All volunteers showed a similar trend across the wavelengths studied irrespective of skin type. The determination of the action spectrum for PUVA-induced erythema is important as it permits reliable estimates of erythemal efficacy of any UVA source where the emission spectrum of the lamp is known or can be measured.


Subject(s)
Erythema/chemically induced , Methoxsalen/adverse effects , PUVA Therapy/adverse effects , Photosensitizing Agents/adverse effects , Action Spectrum , Adult , Aged , Analysis of Variance , Dermatitis, Phototoxic/etiology , Dose-Response Relationship, Radiation , Female , Forearm , Healthy Volunteers , Humans , Male , Methoxsalen/administration & dosage , Middle Aged , Photosensitizing Agents/administration & dosage , Young Adult
11.
Br J Dermatol ; 167(3): 678-87, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22924950

ABSTRACT

BACKGROUND: Psoralen plus ultraviolet A (PUVA) is the standard treatment for early stages of mycosis fungoides. There have been no adequate randomized controlled trials with sufficient power comparing this modality with other therapies. OBJECTIVE: To assess disease response and to compare the response rates of patients treated with PUVA alone or PUVA and bexarotene. METHODS: EORTC 21011 (NCT 00056056) was a randomized phase III study comparing combined bexarotene (Targretin(®) ) and PUVA vs. PUVA alone in patients with stage IB and IIA mycosis fungoides (MF). The primary endpoint was the overall response rate [complete clinical response (CCR) plus partial response (PR)]. RESULTS: The study was prematurely closed due to low accrual after 93 of 145 required patients (65%) were randomized. Of the 93 randomized patients, 87 started treatment, 41 received PUVA and 46 received PUVA + bexarotene. Total UVA doses received were 107 J cm(-2) (range 1·4-489·9) in the PUVA arm vs. 101·7 J cm(-2) (0·2-529·9) in the combination arm. The safety profile was acceptable with few grade 3-4 toxicities observed in either arm. More drop-outs due to toxicity were observed in the combination arm compared with the PUVA-alone arm. The best overall response (CCR + PR) rate was 71% for PUVA alone and 77% for the combination arm (P = 0·57). The median duration of response was 9·7 months for PUVA vs. 5·8 months for the combination arm (P = 0·33). CCR was seen in 25 patients of whom 10 received PUVA alone (CCR 22%) and 15 received combination therapy (CCR 31%) (P = 0·45). CCR was sustained in 25% of patients regardless of therapy. There was a trend towards fewer PUVA sessions needed to achieve CCR in the combination arm (median 22) compared with the PUVA arm (median 27·5) (P = 0·11). Similarly, a trend towards lower UVA dose required to achieve CCR in the combination arm (median 55·8 J cm(-2) ) compared with the PUVA arm alone (median 117·5 J cm(-2) ) (P = 0·5) was observed. CONCLUSIONS: No significant difference in response rate or response duration was observed in this study. However, there was a trend towards fewer PUVA sessions and lower UVA dose required to achieve CCR in the combination arm (PUVA + bexarotene) but this did not achieve statistical significance due to insufficient power.


Subject(s)
Anticarcinogenic Agents/administration & dosage , Mycosis Fungoides/drug therapy , PUVA Therapy/methods , Skin Neoplasms/therapy , Tetrahydronaphthalenes/administration & dosage , Adolescent , Adult , Aged , Anticarcinogenic Agents/adverse effects , Bexarotene , Child , Child, Preschool , Combined Modality Therapy/methods , Dose-Response Relationship, Drug , Dose-Response Relationship, Radiation , Early Termination of Clinical Trials , Humans , Infant , Methoxsalen/administration & dosage , Methoxsalen/adverse effects , Middle Aged , Mycosis Fungoides/pathology , PUVA Therapy/adverse effects , Photosensitizing Agents/administration & dosage , Photosensitizing Agents/adverse effects , Skin Neoplasms/pathology , Tetrahydronaphthalenes/adverse effects , Treatment Outcome , Young Adult
12.
J Eur Acad Dermatol Venereol ; 26 Suppl 3: 22-31, 2012 May.
Article in English | MEDLINE | ID: mdl-22512677

ABSTRACT

BACKGROUND: Oral 8-methoxypsoralen-UV-A (PUVA) and narrowband UV-B (NB-UVB or UVB TL-01) are effective and widely used treatments for chronic plaque psoriasis. Although the role of PUVA therapy in skin carcinogenesis in humans with psoriasis has been clearly demonstrated, there is still controversy regarding the risk of skin cancer with NB-UVB. Furthermore, there is no clear evidence about the maximum cumulative number of sessions not to be exceeded in a lifetime. OBJECTIVES: To assess the respective cutaneous carcinogenic risks of PUVA or NB-UVB in psoriasis; to estimate the respective dose-relationship between skin cancers and PUVA or NB-UVB; to estimate a maximum number of sessions for PUVA or NB-UVB not to be exceeded in a lifetime. METHODS: A systematic literature search was carried out in Medline, Embase and Cochrane Library databases from1980 to December 2010 in English and French, with the keywords 'Psoriasis' AND 'UVB therapy' AND 'UVA therapy' AND 'cancer' AND 'skin' OR 'neoplasm' OR 'cutaneous carcinoma' OR 'melanoma'. RESULTS: Of 243 identified references, 49 published studies were included. Most of them (45/49) concerned PUVA therapy, with 41 assessing the risk of non-melanoma skin cancers (NMSC) following PUVA. All publications referring to the US prospective PUVA follow-up study revealed an increased risk of NMSC with the following characteristics: risk most pronounced for squamous cell carcinomas developing even with low exposures and increasing linearly with the number of sessions, tumors occurring also on non-exposed skin including invasive penile tumors, risk persisting after cessation of treatment. An increased risk of basal cell carcinomas was observed in patients receiving more than hundred PUVA sessions. The four prospective European studies selected in our review and most of the pre-1990 European and US retrospective studies failed to find a link between exposure to PUVA and skin cancer. Only the most recent cohorts, including three large long-term retrospective European studies comparing records with their respective national cancer registries reported on an independent increased risk of NMSC with PUVA, The risk was lower as compared to the US prospective PUVA follow-up study. Six studies assessed the risk of melanoma following PUVA therapy: two of the three US publications coming from the same PUVA prospective follow-up study revealed an increased risk with more than doubled incidence of both invasive and in situ melanoma among patients exposed to at least 200 PUVA treatments compared with patients exposed to lower doses, whereas the three retrospectives European studies, comparing the incidence of melanoma in PUVA users with national cancer registers, did not find any increased risk of melanoma. No increased risk of skin cancer was evidenced in the four studies specifically assessing the potential carcinogenic risk of NB-UVB. CONCLUSION: There is an increased risk of skin cancer following PUVA, shown by both US and European studies. The greater risk measured by the US studies may be at least partly explained by high UVA dose exposure and the lighter phototypes of the treated patients. The lack of prospective studies in psoriasis patients treated with NB-UVB constitutes a barrier to the robust assessment of carcinogenic risk of this phototherapy technique.


Subject(s)
Methoxsalen/therapeutic use , Photochemotherapy/adverse effects , Photosensitizing Agents/therapeutic use , Psoriasis/drug therapy , Skin Neoplasms/etiology , Ultraviolet Rays , Chronic Disease , Female , Humans , Male , Methoxsalen/adverse effects , Photosensitizing Agents/adverse effects , Risk Assessment , Ultraviolet Rays/adverse effects
13.
Photodermatol Photoimmunol Photomed ; 28(1): 34-41, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22212001

ABSTRACT

BACKGROUND/PURPOSE: This study determined the threshold doses for 'solar erythema' and for phototoxic responses to 8-methoxypsoralen (8-MOP) in white skin Hanford and grey skin Yucatan miniature swine. METHODS: For threshold erythema determinations, the UVR exposures included both UVA (315-400 nm) and UVB (290-315 nm) radiation by positioning one fluorescent 'sunlamp' among 10 'PUVA' lamps. With this configuration the UVR exposures ranged from 0.5-2.8 times the 'instrumental MED' (MEDi) for Hanford and from 1.0-5.6 times the MEDi for Yucatan. For phototoxicity determinations (i.e., with and without topically-applied graduated concentrations of 8-MOP), the UVB component was minimized by extinguishing the sunlamp, thus permitting higher UVA exposures. RESULTS: The Hanford had the lower UV erythema dose threshold (1.0-1.4 times the MEDi) and the erythema that developed was readily observable. The exposure doses for the phototoxicity test were 5 J/cm(2) of UVA in 35 minutes or 10 J/cm(2) in 70 minutes. The phototoxic (vascular) response to 8-MOP was observed in the two highest concentrations (0.01% and 0.1%) in Hanford pigs, in a dose-related manner. Microscopic evidence of a dose-related response was also observed as the concentration of 8-MOP increased. CONCLUSION: This verified that the Hanford miniature swine is the preferable strain for phototoxic effects. In contrast, UVR exposure of the Yucatan pig skin produced tanning rather than erythema, confirming that the Yucatan is the more appropriate strain for studying the melanization response. Thus, Hanford and Yucatan miniature swine have cutaneous photobiological responses that reflect their respective strain differences.


Subject(s)
Erythema/chemically induced , Erythema/pathology , Methoxsalen/adverse effects , Photosensitizing Agents/adverse effects , Ultraviolet Rays/adverse effects , Animals , Dose-Response Relationship, Drug , Dose-Response Relationship, Radiation , Drug Evaluation, Preclinical , Female , Humans , Methoxsalen/pharmacology , Photosensitizing Agents/pharmacology , Swine , Swine, Miniature
14.
Photodermatol Photoimmunol Photomed ; 27(6): 294-6, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22092732

ABSTRACT

BACKGROUND: Combination of topical methoxsalen and narrowband ultraviolet B (NBUVB) was shown to be more effective than NBUVB alone in treating plaque-type psoriasis. OBJECTIVE: To find out whether topical methoxsalen and NBUVB had any benefit in induction of remission on treatment-resistant plaques of psoriasis on the legs in comparison with NBUVB alone. METHODS: Ten patients were included. Two symmetric lesions with similar Psoriasis Severity Index score on the lower legs were randomly assigned to be treated with cold cream as placebo or 0.1% 8-methoxypsoralen (8MOP) cream 15 min before phototherapy with NBUVB. Phototherapy was given three times per week for up to three months. Severity scores were recorded each week and side effects were observed before each session. RESULTS: Significant decrease in the severity score was observed in both groups (P-value < 0.001), but none of the lesions cleared completely at the end of the study. The decrease of the score in the 8MOP arm was greater than the control arm; however, the difference was not significant. The only side effect was pigmentation that occurred in all of the 8MOP-treated patients after 2 weeks. CONCLUSION: We could not confirm any significant benefit of topical methoxsalen and NBUVB in comparison to NBUVB alone in treating resistant plaques of psoriasis on the legs.


Subject(s)
Methoxsalen/administration & dosage , Photosensitizing Agents/administration & dosage , Psoriasis/radiotherapy , Ultraviolet Rays , Ultraviolet Therapy , Adult , Aged , Female , Humans , Male , Methoxsalen/adverse effects , Middle Aged , Photosensitizing Agents/adverse effects , Severity of Illness Index , Skin Pigmentation/drug effects , Skin Pigmentation/radiation effects , Time Factors
16.
Ugeskr Laeger ; 173(26): 1869-74, 2011 Jun 27.
Article in Danish | MEDLINE | ID: mdl-21712008

ABSTRACT

During extra corporeal photopheresis (ECP) 1.500 ml blood is extracted. Leucocytes are separated by centrifugation. Methoxsalen is added to the leucocytes and activated by UVA light. After treatment leucocytes are returned to the patient. ECP is a part of the treatment of acute and chronic graft-versus-host disease (GVHD) in bone marrow transplant patients and severe cutaneous T-cell lymphomas (CTLC). Studies have documented an effect of ECP in GVHD and CTLC. ECP has been used to treat other T-cell mediated diseases, the documentation however is sparse. The side effects of ECP are few and not serious.


Subject(s)
Graft vs Host Disease/drug therapy , Lymphoma, T-Cell, Cutaneous/drug therapy , Photopheresis , Skin Neoplasms/drug therapy , Evidence-Based Medicine , Humans , Methoxsalen/administration & dosage , Methoxsalen/adverse effects , Photopheresis/adverse effects , Photopheresis/methods , Photosensitizing Agents/administration & dosage , Photosensitizing Agents/adverse effects , Treatment Outcome
18.
An Bras Dermatol ; 85(4): 571-2, 2010.
Article in English, Portuguese | MEDLINE | ID: mdl-20944925

ABSTRACT

Two adolescent females and a girl, all with clinically diagnosed vitiligo, were treated with 0.2% 8-methoxypsoralen cream followed by exposure to solar ultraviolet light. One year later, they developed hypopigmented and achromic spots on the areas affected by the vitiligo. Biopsy of skin tissue taken from one of these cases showed a marked reduction in melanin. Clinical and histological findings point to a diagnosis of leukoderma punctata.


Subject(s)
Methoxsalen/adverse effects , PUVA Therapy/adverse effects , Photosensitizing Agents/adverse effects , Pigmentation Disorders/etiology , Adolescent , Child , Female , Humans , Methoxsalen/therapeutic use , Photosensitizing Agents/therapeutic use , Pigmentation Disorders/pathology , Vitiligo/drug therapy
19.
Article in English | MEDLINE | ID: mdl-20826993

ABSTRACT

BACKGROUND: Psoralen UV-A (PUVA) is an established therapy for psoriasis, but there is a well-documenated risk of melanoma and nonmelanoma skin cancer. Narrow-band Ultraviolet-B (NBUVB) therapy has a lower carcinogenic risk, has equal therapeutic potential and is considerably safe in the long term than PUVA. AIM: The aim of present study was to compare the efficacy and side-effects of PUVA and NBUVB in chronic plaque psoriasis. METHODS: Sixty patients of chronic plaque psoriasis were taken up for the study and were randomly divided into two groups of 30 each. They were well matched in terms of age, sex, psoriasis extent and pretreatment psoriasis area severity index (PASI) scoring. One group was treated with twice-weekly narrow-band UV-B (TL-01) phototherapy and the other group received twice-weekly oral 8-Methoxsalen PUVA for a period of 3 months. RESULTS: Both the groups achieved >75% reduction in the PASI score or complete clearance at the end of 3 months, but PUVA group patients required significantly fewer number of treatment sessions and fewer number of days to clear the psoriasis as compared to the NBUVB group, while the mean cumulative clearance dose and adverse effects were significantly lower in the NBUVB group. CONCLUSION: We concluded that PUVA group patients achieved a faster clearance, but the adverse effects were significantly lower in the NBUVB group.


Subject(s)
Methoxsalen/administration & dosage , PUVA Therapy/methods , Photosensitizing Agents/administration & dosage , Phototherapy/methods , Psoriasis/drug therapy , Adolescent , Adult , Chronic Disease , Female , Humans , Male , Methoxsalen/adverse effects , Middle Aged , PUVA Therapy/adverse effects , Photosensitizing Agents/adverse effects , Phototherapy/adverse effects , Treatment Outcome , Young Adult
20.
An. bras. dermatol ; 85(4): 571-572, jul.-ago. 2010. ilus
Article in Portuguese | LILACS | ID: lil-560595

ABSTRACT

Duas adolescentes e uma menina com vitiligo clinicamente diagnosticado foram tratadas com 8-metoxipsoraleno a 0,2 por cento em creme Lanette com subsequente exposição solar. Um ano após, apresentaram máculas acrômicas na área do vitiligo. A biópsia de pele em um dos casos revelou melanócitos com escassa pigmentação melânica. Os achados clínicos e histológicos sugerem o diagnóstico de leucodermia punctata.


Two adolescent females and a girl, all with clinically diagnosed vitiligo, were treated with 0.2 percent 8-methoxypsoralen cream followed by exposure to solar ultraviolet light. One year later, they developed hypopigmented and achromic spots on the areas affected by the vitiligo. Biopsy of skin tissue taken from one of these cases showed a marked reduction in melanin. Clinical and histological findings point to a diagnosis of leukoderma punctata.


Subject(s)
Adolescent , Child , Female , Humans , Methoxsalen/adverse effects , PUVA Therapy/adverse effects , Photosensitizing Agents/adverse effects , Pigmentation Disorders/etiology , Methoxsalen/therapeutic use , Photosensitizing Agents/therapeutic use , Pigmentation Disorders/pathology , Vitiligo/drug therapy
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