Hexyl aminolevulinate, 5-aminolevulinic acid nanoemulsion and methyl aminolevulinate in photodynamic therapy of non-aggressive basal cell carcinomas: A non-sponsored, randomized, prospective and double-blinded trial.

BACKGROUND: In the photodynamic therapy (PDT) of non-aggressive basal cell carcinomas (BCCs), 5-aminolevulinic acid nanoemulsion (BF-200ALA) has shown non-inferior efficacy when compared with methyl aminolevulinate (MAL), a widely used photosensitizer. Hexyl aminolevulinate (HAL) is an interesting alternative photosensitizer. To our knowledge, this is the first study using HAL-PDT in the treatment of BCCs. OBJECTIVES: To compare the histological clearance, tolerability (pain and post-treatment reaction) and cosmetic outcome of MAL, BF-200 ALA and low-concentration HAL in the PDT of non-aggressive BCCs. METHODS: Ninety-eight histologically verified non-aggressive BCCs met the inclusion criteria, and 54 patients with 95 lesions completed the study. The lesions were randomized to receive LED-PDT in two repeated treatments with MAL, BF-200 ALA or HAL. Efficacy was assessed both clinically and confirmed histologically at three months by blinded observers. Furthermore, cosmetic outcome, pain, post-treatment reactions fluorescence and photobleaching were evaluated. RESULTS: According to intention-to-treat analyses, the histologically confirmed lesion clearance was 93.8% (95% confidence interval [CI] = 79.9-98.3) for MAL, 90.9% (95% CI = 76.4-96.9) for BF-200 ALA and 87.9% (95% CI = 72.7-95.2) for HAL, with no differences between the arms (P = 0.84). There were no differences between the arms as regards pain, post-treatment reactions or cosmetic outcome. CONCLUSIONS: Photodynamic therapy with low-concentration HAL and BF-200 ALA has a similar efficacy, tolerability and cosmetic outcome compared to MAL. HAL is an interesting new option in dermatological PDT, since good efficacy is achieved with a low concentration.

Ablative fractional laser-assisted photodynamic therapy for lentigo maligna: a prospective pilot study.

BACKGROUND: Lentigo maligna (LM) is an in situ form of melanoma carrying a risk of progression to invasive lentigo maligna melanoma (LMM). LM poses a clinical challenge, with subclinical extension and high recurrence rates after incomplete surgery. Alternative treatment methods have been investigated with varying results. Photodynamic therapy (PDT) with methylaminolaevulinate (MAL) has already proved promising in this respect. OBJECTIVES: To investigate the efficacy of ablative fractional laser (AFL)-assisted PDT with 5-aminolaevulinic acid nanoemulsion (BF-200 ALA) for treating LM. METHODS: In this non-sponsored prospective pilot study, ten histologically verified LMs were treated with AFL-assisted PDT three times at 2-week intervals using a light dose of 90 J/cm2 per treatment session. Local anaesthesia with ropivacaine was used. Four weeks after the last PDT treatment the lesions were treated surgically with a wide excision and sent for histopathological examination. The primary outcome was complete histopathological clearance of the LM from the surgical specimen. Patient-reported pain during illumination and the severity of the skin reaction after the PDT treatments were monitored as secondary outcomes. RESULTS: The complete histopathological clearance rate was 7 out of 10 LMs (70%). The pain during illumination was tolerable, with the mean pain scores for the PDT sessions on a visual assessment scale ranging from 2.9 to 3.8. Some severe skin reactions occurred during the treatment period, however. CONCLUSIONS: Ablative fractional laser-assisted PDT showed moderate efficacy in terms of histological clearance. It could constitute an alternative treatment for LM but due to the side effects it should only be considered in inoperable cases.

Tumor cell-specific Serpin A1 expression in vulvar squamous cell carcinoma.

PURPOSE: The two main etiological factors for vulvar squamous cell carcinoma (vSCC) are the vulvar dermatosis lichen sclerosus (LS) and high-risk human papillomavirus (hrHPV). Serpin A1 (α1-antitrypsin) is a serine protease inhibitor, which plays a role in the tumorigenesis of various cancer types. The aim of the study was to evaluate the expressions of Serpin A1 in LS, premalignant vulvar lesions, and vSCC using immunohistochemistry (IHC) and serum analysis, and to compare Serpin A1 stainings to the tumor markers p53 and p16. METHODS: In total, 120 samples from 74 patients were studied with IHC for Serpin A1, p53 and p16: 18 normal vulvar skin, 53 LS, 9 premalignant vulvar lesions (dVIN/HSIL) and 40 vSCC samples. Serum concentrations of Serpin A1 were analyzed from 30 LS, 44 vSCC and 10 control patients. Expressions were compared to clinical data. RESULTS: Tumor cell-specific Serpin A1 overexpression was detected in 88% of vSCC samples, independent of the etiology. The intensity of Serpin A1 expression was significantly higher in vSCC than in healthy vulvar skin, LS, or premalignant vulvar lesions. Serpin A1 showed an association with p53 positivity. No difference in overall survival was found between Serpin A1-, p53-, or p16-positive vSCC patients. Serum concentrations of Serpin A1 were equal in the LS, vSCC, and control groups. CONCLUSION: Tumor cell-specific Serpin A1 overexpression is a potential biomarker in vSCC.

Hyperspectral imaging system in the delineation of Ill-defined basal cell carcinomas: a pilot study.

BACKGROUND: Basal cell carcinoma (BCC) is the most common skin cancer in the Caucasian population. Eighty per cent of BCCs are located on the head and neck area. Clinically ill-defined BCCs often represent histologically aggressive subtypes, and they can have subtle subclinical extensions leading to recurrence and the need for re-excisions. OBJECTIVES: The aim of this pilot study was to test the feasibility of a hyperspectral imaging system (HIS) in vivo in delineating the preoperatively lateral margins of ill-defined BCCs on the head and neck area. METHODS: Ill-defined BCCs were assessed clinically with a dermatoscope, photographed and imaged with HIS. This was followed by surgical procedures where the BCCs were excised at the clinical border and the marginal strip separately. HIS, with a 12-cm2 field of view and fast data processing, records a hyperspectral graph for every pixel in the imaged area, thus creating a data cube. With automated computational modelling, the spectral data are converted into localization maps showing the tumour borders. Interpretation of these maps was compared to the histologically verified tumour borders. RESULTS: Sixteen BCCs were included. Of these cases, 10 of 16 were the aggressive subtype of BCC and 6 of 16 were nodular, superficial or a mixed type. HIS delineated the lesions more accurately in 12 of 16 of the BCCs compared to the clinical evaluation (4 of 16 wider and 8 of 16 smaller by HIS). In 2 of 16 cases, the HIS-delineated lesion was wider without histopathological confirmation. In 2 of 16 cases, HIS did not detect the histopathologically confirmed subclinical extension. CONCLUSIONS: HIS has the potential to be an easy and fast aid in the preoperative delineation of ill-defined BCCs, but further adjustment and larger studies are warranted for an optimal outcome.

5-aminolaevulinic acid nanoemulsion is more effective than methyl-5-aminolaevulinate in daylight photodynamic therapy for actinic keratosis: a nonsponsored randomized double-blind multicentre trial.

BACKGROUND: Daylight photodynamic therapy (DL-PDT) with methyl-5-aminolaevulinate (MAL) is an effective treatment for mild and moderate actinic keratosis (AK). OBJECTIVES: To assess the clinical efficacy, tolerability and cost-effectiveness of 5-aminolaevulinic acid nanoemulsion (BF-200 ALA) compared with MAL in DL-PDT for grade I-II AKs. METHODS: This nonsponsored, prospective randomized double-blind multicentre trial included 69 patients with 767 grade I-II AKs located symmetrically on the face or scalp. A single DL-PDT was given in a randomized split-face design. The primary outcome was clearance of the AKs at 12 months as assessed by a blinded observer. The secondary outcomes were pain, treatment reactions, cosmetic outcome and the cost-effectiveness of the therapy. RESULTS: In the per-patient (half-face) analysis, clearance was better for the BF-200 ALA sides than for those treated with MAL (P = 0·008). In total, BF-200 ALA cleared 299/375 AKs (79·7%) and MAL 288/392 (73·5%) (P = 0·041). The treatment was practically painless with both photosensitizers, the mean pain visual analogue scale being 1·51 for BF-200 ALA and 1·35 for MAL (P = 0·061). Twenty-six patients had a stronger skin reaction on the BF-200 ALA side, seven on the MAL side and 23 displayed no difference (P = 0·001). The cosmetic outcome was excellent or good in > 90% of cases with both photosensitizers (P = 1·000). The cost-effectiveness plane showed that the costs of DL-PDT were similar for both photosensitizers, but the effectiveness was slightly higher for BF-200 ALA. CONCLUSIONS: Our results indicate that BF-200 ALA is more effective than MAL in DL-PDT for grade I-II AKs. BF-200 ALA provides slightly better value for money than MAL.

Reduction in ERRα is associated with lichen sclerosus and vulvar squamous cell carcinoma.

OBJECTIVE: ERRs (estrogen-related receptors) regulate energy metabolism, the cell cycle and inflammatory processes in both normal and cancer cells. Chronic inflammation induced by lichen sclerosus (LS) or human papilloma virus (HPV) precedes vulvar squamous cell carcinoma (vulvar SCC). We investigated the expression of ERRα, ERRß and ERRγ in normal vulvar skin, LS as well as LS-dependent and LS-independent/HPV-related vulvar SCC. METHODS: A total of 203 samples were analyzed for ERRα, ERRß and ERRγ by using immunohistochemistry. These included 37 normal vulvar skin samples, 110 LS samples, 6 vulvar intraepithelial neoplasia (VIN) samples and 50 vulvar SCC samples. RESULTS: A substantial reduction in or disappearance of ERRα was detected in all vulvar SCC samples. A total of 79% of childhood-onset LS and 51% of adulthood-onset LS lesions showed decreases in ERRα staining. A gradual reduction in ERRα cytoplasmic staining was observed from healthy vulvar skin to precursor lesions and further to SCC. Nuclear ERRα staining was observed in 8/33 (24%) LS-dependent and 10/17 (59%) LS-independent SCC samples. CONCLUSIONS: ERRα, a key regulator of cell energy metabolism, may play a role in the pathogenesis of both LS and vulvar SCC.

Daylight photodynamic therapy for actinic keratoses: a randomized double-blinded nonsponsored prospective study comparing 5-aminolaevulinic acid nanoemulsion (BF-200) with methyl-5-aminolaevulinate.

BACKGROUND: Daylight-mediated photodynamic therapy (DL-PDT) using methyl-5-aminolaevulinate (MAL) is effective for thin, grade I, actinic keratoses (AK). There are no published studies of other photosensitizers used in DL-PDT. OBJECTIVES: To compare the efficacy and adverse effects of 5-aminolaevulinic acid nanoemulsion (BF-200 ALA) with MAL in DL-PDT of grade I-III AKs. METHODS: In 13 patients, 177 AKs were randomized symmetrically for a split-face prospective observer-blinded study and received either BF-200 ALA or MAL DL-PDT. Grade I AKs were treated once and grade II-III AKs twice with a 0·25-mm layer of photosensitizer precursors. Pain was assessed during and after the daylight exposure. Efficacy at 3 months was assessed clinically and histologically. RESULTS: BF-200 ALA cleared 71/84 (84·5%) and MAL 69/93 (74·2%) of the AKs (P = 0·099), all grades responding equally, but with new AKs appearing during follow-up (n = 4, BF-200 ALA; n = 8, MAL). In per patient half-face analysis BF-200 ALA showed significantly higher clearance rates for grade I AKs than did MAL (P = 0·027), but for thicker grades, clearance was equal (P = 0·564). BF-200 ALA and MAL treatments resulted in 61·5% and 38·5% complete histological clearance (P = 0·375), respectively. p53 expression decreased by 54·4% and 33·7%, respectively (P = 0·552). Both treatments were nearly painless with similar adverse reactions and no difference in patient preference. CONCLUSIONS: BF-200 ALA showed a trend towards improved efficacy results compared with MAL. Thicker lesions in both groups responded when treated repeatedly. Importantly, a thin 0·25-mm layer of the photosensitizer precursors was sufficient, which may lead to lower expense.

Experimentally induced psoriatic lesion associates with interleukin (IL)-6 in mast cells and appearance of dermal cells expressing IL-33 and IL-6 receptor.

Mast cells are involved in the development of psoriatic lesion, but it is not known how mast cells are activated or whether mast cell cytokines are expressed during the lesion development. In this study, the Köbner reaction was induced in uninvolved psoriatic skin of 18 patients using the tape-stripping technique, and a sequence of biopsies was collected at 0 days, 2 h and 3 days or at 0 days, 1 day and 7 days for histochemical analysis. Eight patients developed the Köbner reaction verified at the follow-up visit 2-2·5 weeks later. No significant differences were observed in total tryptase(+) mast cells, psoriasis area and severity index and age/sex. Instead, the percentage of tryptase(+) mast cells showing interleukin (IL)-6 immunoreactivity was significantly higher in biopsies from Köbner-positive patients than in those from Köbner-negative patients. IL-33 is a known inducer of IL-6 in mast cells, and the number of IL-33(+) cells increased significantly in Köbner-positive dermal skin at days 3-7. The number of dermal cells with IL-6 receptor (IL-6R, CD126) also increased in Köbner-positive skin at days 3-7. Unexpectedly, the number of IL-6R(+) cells was even higher in Köbner-negative skin at days 3-7. In the chronic plaque of 10 other psoriatic patients, the numbers of IL-6(+) mast cells and dermal cells showing IL-6R were higher than those in the non-lesional skin. In conclusion, the positive Köbner reaction is associated with IL-6 in mast cells and appearance of IL-6R(+) and IL-33(+) dermal cells. This suggests that a previously unrecognized vicious circle may develop in the early psoriatic lesion.

Comparison of narrowband ultraviolet B exposure and oral vitamin D substitution on serum 25-hydroxyvitamin D concentration.

BACKGROUND: A short course of narrowband ultraviolet B (NB-UVB) exposures increases the serum 25-hydroxyvitamin D [25(OH)D] concentration in patients with psoriasis and healthy subjects. OBJECTIVES: To compare the effects of NB-UVB and oral vitamin D substitution in healthy subjects in winter. METHODS: Healthy adult hospital employees and medical students were screened for serum 25(OH)D concentration. Those with 25(OH)D below 75 nmol L(-1) were randomly given either 12 NB-UVB exposures or 20 µg of oral cholecalciferol daily for 4 weeks. The NB-UVB exposures were given with a Waldmann UV 7001 cabin and the mean cumulative dose was 48·4 standard erythema doses. Serum 25(OH)D was measured before and after the treatments by radioimmunoassay. RESULTS: The baseline serum 25(OH)D concentrations were 52·9 ± 10·4 (mean ± SD) in the 33 NB-UVB-treated and 53·5 ± 12·7 nmol L(-1) in the 30 oral cholecalciferol-treated subjects. The mean increase in serum 25(OH)D was 41·0 nmol L(-1) [95% confidence interval (CI) 34·8-47·2; P < 0·001] in the NB-UVB group and 20·2 nmol L(-1) (95% CI 14·6-26·0; P < 0·001) in the cholecalciferol group. The difference between the two treatments was significant at 2 weeks (P = 0·033) and at 4 weeks (P < 0·001). One month after the treatments the 25(OH)D concentrations had increased further. CONCLUSIONS: The present study shows that 12 NB-UVB exposures given during 4 weeks increase serum 25(OH)D concentration significantly more than 20 µg of oral cholecalciferol daily. A short NB-UVB course is an effective way to improve vitamin D balance in winter and the response is still evident 2 months after the course.

Narrowband ultraviolet B treatment improves vitamin D balance and alters antimicrobial peptide expression in skin lesions of psoriasis and atopic dermatitis.

BACKGROUND: Narrowband ultraviolet B (NB-UVB) is a routine treatment for psoriasis and atopic dermatitis (AD) but its effect on vitamin D balance is not well studied. OBJECTIVES: To examine whether NB-UVB treatment in winter improves vitamin D balance in psoriasis and AD, and to study the effects of NB-UVB on antimicrobial peptide and cytokine expression in the skin. METHODS: Eighteen adult patients with psoriasis, 18 with AD and 15 healthy subjects received a total of 15 NB-UVB exposures on the whole body, given three times a week. Serum calcidiol (25-hydroxyvitamin D) was measured by radioimmunoassay. Antimicrobial peptide and cytokine expression in skin lesions was examined by real-time quantitative polymerase chain reaction. RESULTS: At onset 16 (89%) patients with psoriasis, 17 (94%) patients with AD and eight (53%) healthy subjects had vitamin D insufficiency (calcidiol < 50 nmol L(-1)). NB-UVB treatment significantly increased (P < 0.001) serum calcidiol. The increase was 59.9 nmol L(-1) (95% confidence interval, CI 53.5-66.9) in psoriasis, 68.2 nmol L(-1) (95% CI 55.4-80.1) in AD and 90.7 nmol L(-1) (95% CI 63.8-123.4) in healthy subjects. Psoriasis Area and Severity Index and SCORAD improved significantly (P < 0.001) but no correlation to the increase of serum calcidiol was found. Cathelicidin and human beta-defensin 2 (HBD2) expression was high in skin lesions of psoriasis. After six NB-UVB treatments cathelicidin increased further while HBD2 expression decreased. A similar trend was observed in AD lesions. NB-UVB caused a marked but nonsignificant decrease of interleukin (IL)-1beta and IL-17 in psoriasis lesions. CONCLUSIONS: The present study shows that in addition to a significant improvement of psoriasis and AD, NB-UVB treatment effectively corrects vitamin D insufficiency. It also increases cathelicidin and decreases HBD2 levels in healing skin lesions of psoriasis and AD. This effect might be mediated by improved vitamin D balance and the local cytokine network.

Narrowband ultraviolet B course improves vitamin D balance in women in winter.

BACKGROUND: Vitamin D insufficiency is common in winter in the Nordic countries. OBJECTIVES: To examine whether a short course of narrowband ultraviolet B (NB-UVB) improves vitamin D balance. METHODS: Fifty-six healthy, white women (mean age 41 years) volunteered and 53 completed the study. NB-UVB exposures were given on seven consecutive days either on the whole body (n = 19), on the head and arms (n = 9) or on the abdomen (n = 14). Similarly, seven solar simulator exposures were given on the face and arms (n = 11). The cumulative UVB dose was 13 standard erythema doses in all regimens. Serum calcidiol (25-hydroxyvitamin D) concentration was measured by radioimmunoassay before and after the NB-UVB exposures. Follow-up samples were taken from the whole-body NB-UVB group at 2 months. RESULTS: At onset 41 women (77%) had vitamin D insufficiency (calcidiol < 50 nmol L(-1)) and six (11%) had vitamin D deficiency (calcidiol < 25 nmol L(-1)). Calcidiol concentration increased significantly, by a mean of 11.4 nmol L(-1) when NB-UVB was given on the whole body, by 11.0 nmol L(-1) when given on the head and arms and by 4.0 nmol L(-1) when given on the abdomen. Solar simulator exposures given on the face and arms increased calcidiol by 3.8 nmol L(-1). After 2 months serum calcidiol was still higher than initially in the group who received NB-UVB exposures on the whole body. CONCLUSIONS: NB-UVB exposures given on seven consecutive days on different skin areas of healthy women significantly improved serum calcidiol concentration. A short low-dose NB-UVB course can improve vitamin D balance in winter.

Heliotherapy improves vitamin D balance and atopic dermatitis.

BACKGROUND: Vitamin D insufficiency during winter is common in the Nordic countries. Heliotherapy (HT) may heal atopic dermatitis (AD) but its effect on vitamin D balance has not been examined. OBJECTIVES: To study the effect of HT on serum calcidiol (25-hydroxyvitamin D) concentration and on healing of AD. METHODS: Twenty-three adult patients with AD received a 2-week course of HT in the Canary Islands in either January or March 2005. Daily solar ultraviolet (UV) radiation was measured and personal UV exposure calculated as standard erythema doses (SED). Blood samples were taken during HT and during a 1-2 month follow-up. Serum calcidiol concentration was measured by radioimmunoassay. Healing of AD was examined by SCORAD index. RESULTS: Before HT 17 (74%) AD patients had vitamin D insufficiency (calcidiol < 50 nmol L(-1)) and four patients high (> 80 nmol L(-1)) serum calcidiol values. The median personal UV dose during the 2-week HT course was 60 SED in the January group and 109 SED in the March group. Serum calcidiol concentration increased significantly in both groups, by 13.4 and 24.0 nmol/L(-1), respectively, and after HT only four (17%) patients had vitamin D insufficiency. SCORAD improved from 34 to 9 in the January HT group and from 30 to 9 in the March group. CONCLUSIONS: A 2-week course of HT significantly improved vitamin D balance by increasing serum calcidiol concentration, and caused a marked healing of AD. These parallel positive responses should be taken into account when the benefits of HT are considered.

Efficacy and safety of a new combination of calcipotriol and betamethasone dipropionate (once or twice daily) compared to calcipotriol (twice daily) in the treatment of psoriasis vulgaris: a randomized, double-blind, vehicle-controlled clinical trial.

BACKGROUND: Calcipotriol and betamethasone dipropionate are both widely used, effective treatments for psoriasis. Vitamin D analogues and topical corticosteroids have different mechanisms of action in the treatment of psoriasis. A new vehicle has been developed in order to contain both calcipotriol (50 micro g g-1) and betamethasone dipropionate (0.5 mg g-1) in an ointment form. By using calcipotriol and a corticosteroid together, greater efficacy may be achieved than by using either compound alone. OBJECTIVES: The present study was conducted in order to compare the clinical efficacy and safety of the combined ointment formulation used once daily with the vehicle ointment used twice daily, calcipotriol ointment used twice daily and the combined formulation used twice daily in psoriasis vulgaris. METHODS: This was an international, multicentre, prospective, randomized, double-blind, vehicle-controlled, parallel group, 4-week study in patients with psoriasis vulgaris amenable to topical treatment. Patients were randomized to one of four treatment groups: combined formulation once daily, combined formulation twice daily, calcipotriol twice daily or vehicle twice daily. Efficacy and safety were assessed. RESULTS: There was no statistically significant difference in the mean percentage change in the Psoriasis Area and Severity Index (PASI) from baseline to end of treatment between the two combined formulation groups, but the difference in PASI reduction was significantly higher in the combined formulation groups (68.6% once daily, 73.8% twice daily) than in both the twice daily calcipotriol group (58.8%) and the vehicle group (26.6%). Safety data showed the frequency of adverse events to be less in the combined formulation groups than in both the calcipotriol group and the vehicle group. The proportion of patients with lesional/perilesional adverse reactions was less in the combined formulation groups and vehicle group than in the calcipotriol group (9.9% combined formulation once daily, 10.6% combined formulation twice daily, 19.8% calcipotriol, 12.5% vehicle). CONCLUSIONS: No statistically significant nor clinically relevant difference in efficacy was seen between the combined formulation used once daily and twice daily. When compared to vehicle ointment or calcipotriol ointment alone, the combined formulation was shown to be clearly more efficacious.

Kinetics of phototoxicity in trioxysalen bath psoralen plus ultraviolet A photochemotherapy.

A trioxysalen bath is a safe alternative to systemic 8-methoxypsoralen in long-term psoralen plus ultraviolet A (PUVA) treatment. The kinetics of its main side-effect, the strong phototoxicity, has not been thoroughly studied. This study determined the degree and persistence of phototoxicity after a single 10 min bath at a trioxysalen concentration of 0.33 mg/l. The buttock skin of 16 healthy volunteers was irradiated with UVA 10 min, and 1, 3, 9 and 24h after the bath. The minimal phototoxic dose (MPD) was assessed 48, 72 and 96h after the bath. In general, the 96 h reading showed the lowest values of MPD; for example, a median of 0.14 J/cm2 (95% confidence interval 0.10-0.14 J/cm2) at sites irradiated 10 min after the bath. The values increased progressively with later irradiation, and the maximum dose applied, 18.32 J/cm2, failed to produce any redness when irradiation was given 24 h after the bath. Substantial phototoxicity persists up to at least 9h after the trioxysalen bath, making it wise for patients to avoid sunshine for at least the rest of the day.

XPD exon 10 and 23 polymorphisms and DNA repair in human skin in situ.

Forty-four Finnish volunteers who were previously studied with regard to the repair rate of UV-specific cyclobutane pyrimidine dimers in the skin were genotyped for XPD polymorphisms at codons 312 (exon 10 G-->A, Asp-->Asn) and 751 (exon 23 A-->C, Lys-->Gln). The repair rate was measured at 24 h for two different cyclobutane dimers. The data did not show consistent XPD genotype-specific differences in DNA repair rates among all subjects. The combined exon 10 AA and exon 23 CC genotype was associated with an approximately 50% depression of repair rate but this was of borderline statistical significance. However, the exon 23 C allele was associated with depressed repair among subjects aged 50 years or older and the result was consistent with both dimers.

Metalloelastase (MMP-12) and 92-kDa gelatinase (MMP-9) as well as their inhibitors, TIMP-1 and -3, are expressed in psoriatic lesions.

In skin biology, matrix metalloproteinases (MMPs) have been implicated in inflammatory matrix remodeling, neovascularization, wound healing and malignant transformation. Psoriasis is histologically characterized by keratinocyte hyperproliferation, infiltration of inflammatory cells, neoangiogenesis and production of cytokines, such as TNF-alpha, IL-1beta, TGF-alpha, and IFN-gamma, also capable of regulating MMP transcription. To investigate the role of stromelysins-1 and -2, matrilysin, metalloelastase, collagenases-1 and -3 and 92-kDa gelatinase as well as their inhibitors, TIMPs-1 and -3, in psoriasis, we performed in situ hybridization using 35S-labeled cRNA probes on 29 psoriatic lesions and 9 samples of normal looking skin from psoriatic patients. Metalloelastase mRNA was detected in 21/27 samples in macrophages that had migrated into the epidermis or in the inflammatory infiltrates of the superficial dermis. A quantity of 92-kDa gelatinase was found in macrophages and neutrophils (25/27). Stromelysin-1 mRNA was detected in basal keratinocytes in 4/21 lesions. Intracellular laminin-5 immunosignal in basal keratinocytes of the same samples, suggested that stromelysin-1 might participate in remodeling of the basement membrane zone. No signal for stromelysin-2 or collagenase-3 was found and only sweat glands were positive for matrilysin. TIMP-1 was more abundantly expressed than TIMP-3 in the inflammatory infiltrates and endothelial cells of dermal papillae (22/29). TIMP-3 was expressed perivascularly in 9/16 samples. Our results suggest that overexpression of the investigated MMPs by keratinocytes is not associated with psoriasis. However, macrophages express MMPs in psoriatic skin. Also TIMPs, particularly TIMP-1, were abundantly expressed, suggesting that mere MMP overexpression is unlikely to contribute to psoriatic tissue changes.

Concentration-dependent phototoxicity in trimethylpsoralen bath psoralen ultraviolet A.

BACKGROUND: Long-term use of topical trimethylpsoralen (TMP) psoralen bath plus ultraviolet A (bath PUVA) is considered safe with regard to the risk of skin cancer. However, the potential for severe phototoxicity limits its use. OBJECTIVES: To study the effect of dilution of the TMP bath on the minimal phototoxic dose (MPD). METHODS: Fifteen volunteers participated in the study. The MPD tests were performed for three TMP concentrations: 0.33 mg L-1, 0.1 mg L-1 and 0.033 mg L-1 at 2-week intervals. Geometric UVA dose series increasing by a factor of radical2 were used for the testing on the previously unexposed buttock skin. The MPD72 h was assessed at 72 h from the bath. RESULTS: For the highest TMP concentration of 0.33 mg L-1, the median MPD72 h was 0.14 J cm-2 (95% confidence interval (CI), 0.10-0.14 J cm-2). For the diluted TMP bath concentration of 0.1 mg L-1, the median MPD72 h increased to 0.29 J cm-2 (95% CI, 0.2-0.41 J cm-2) and for 0.033 mg L-1 to 0.81 J cm-2 (95% CI, 0.57-1.15 J cm-2), respectively. Thus, diluting the labelled concentration of 0.33 mg L-1 1 : 10 increased the median MPD72 h 5.6-fold. CONCLUSIONS: With regard to the safety and practicality of the TMP bath PUVA, the lower concentrations of TMP may be of clinical importance, and this needs to be validated in future controlled clinical trials.