Sunscreen applied at ≥ 2 mg cm-2 during a sunny holiday prevents erythema, a biomarker of ultraviolet radiation-induced DNA damage and suppression of acquired immunity.

BACKGROUND: Sun protection factor (SPF) is assessed with sunscreen applied at 2 mg cm-2 . People typically apply around 0·8 mg cm-2 and use sunscreen daily for holidays. Such use results in erythema, which is a risk factor for skin cancer. OBJECTIVES: To determine (i) whether typical sunscreen use resulted in erythema, epidermal DNA damage and photoimmunosuppression during a sunny holiday, (ii) whether optimal sunscreen use inhibited erythema and (iii) whether erythema is a biomarker for photoimmunosuppression in a laboratory study. METHODS: Holidaymakers (n = 22) spent a week in Tenerife (very high ultraviolet index) using their own sunscreens without instruction (typical sunscreen use). Others (n = 40) were given SPF 15 sunscreens with instructions on how to achieve the labelled SPF (sunscreen intervention). Personal ultraviolet radiation (UVR) exposure was monitored electronically as the standard erythemal dose (SED) and erythema was quantified. Epidermal cyclobutane pyrimidine dimers (CPDs) were determined by immunostaining, and immunosuppression was assessed by contact hypersensitivity (CHS) response. RESULTS: There was no difference between personal UVR exposure in the typical sunscreen use and sunscreen intervention groups (P = 0·08). The former had daily erythema on five UVR-exposed body sites, increased CPDs (P < 0·001) and complete CHS suppression (20 of 22). In comparison, erythema was virtually absent (P < 0·001) when sunscreens were used at ≥ 2 mg cm-2 . A laboratory study showed that 3 SED from three very different spectra suppressed CHS by around ~50%. CONCLUSIONS: Optimal sunscreen use prevents erythema during a sunny holiday. Erythema predicts suppression of CHS (implying a shared action spectrum). Given that erythema and CPDs share action spectra, the data strongly suggest that optimal sunscreen use will also reduce CPD formation and UVR-induced immunosuppression.

Optimal sunscreen use, during a sun holiday with a very high ultraviolet index, allows vitamin D synthesis without sunburn.

BACKGROUND: Sunlight contains ultraviolet (UV)A and UVB radiation. UVB is essential for vitamin D synthesis but is the main cause of sunburn and skin cancer. Sunscreen use is advocated to reduce the sun's adverse effects but may compromise vitamin D status. OBJECTIVES: To assess the ability of two intervention sunscreens to inhibit vitamin D synthesis during a week-long sun holiday. METHODS: The impact of sunscreens on vitamin D status was studied during a 1-week sun holiday in Tenerife (28° N). Comparisons were made between two formulations, each with a sun protection factor (SPF) of 15. The UVA-protection factor (PF) was low in one case and high in the other. Healthy Polish volunteers (n = 20 per group) were given the sunscreens and advised on the correct application. Comparisons were also made with discretionary sunscreen use (n = 22) and nonholiday groups (51·8° N, n = 17). Sunscreen use in the intervention groups was measured. Behaviour, UV radiation exposure, clothing cover and sunburn were monitored. Serum 25-hydroxyvitamin D3 [25(OH)D3 ] was assessed by high-performance liquid chromatography-tandem mass spectrometry. RESULTS: Use of intervention sunscreens was the same (P = 0·60), and both equally inhibited sunburn, which was present in the discretionary use group. There was an increase (P < 0·001) in mean ± SD 25(OH)D3 (28·0 ± 16·5 nmol L-1 ) in the discretionary use group. The high and low UVA-PF sunscreen groups showed statistically significant increases (P < 0·001) of 19·0 ± 14·2 and 13·0 ± 11·4 nmol L-1 25(OH)D3 , respectively with P = 0·022 for difference between the intervention sunscreens. The nonholiday group showed a fall (P = 0·08) of 2·5 ± 5·6 nmol L-1 25(OH)D3 . CONCLUSIONS: Sunscreens may be used to prevent sunburn yet allow vitamin D synthesis. A high UVA-PF sunscreen enables significantly higher vitamin D synthesis than a low UVA-PF sunscreen because the former, by default, transmits more UVB than the latter. What's already known about this topic? Action spectra (wavelength dependence) for erythema and the cutaneous formation of vitamin D overlap considerably in the ultraviolet (UV)B region. Theoretically, sunscreens that inhibit erythema should also inhibit vitamin D synthesis. To date, studies on the inhibitory effects of sunscreens on vitamin D synthesis have given conflicting results, possibly, in part, because people typically apply sunscreen suboptimally. Many studies have design flaws. What does this study add? Sunscreens (sun protection factor, SPF 15) applied at sufficient thickness to inhibit sunburn during a week-long holiday with a very high UV index still allow a highly significant improvement of serum 25-hydroxyvitamin D3 concentration. An SPF 15 formulation with high UVA protection enables better vitamin D synthesis than a low UVA protection product. The former allows more UVB transmission.

Endoplasmic reticulum aminopeptidase 1 polymorphism Ile276Met is associated with atopic dermatitis and affects the generation of an HLA-C associated antigenic epitope in vitro.

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disease of complex aetiology, with interactions between susceptibility genes and environmental factors. We have previously described a protective effect of the KIR2DS1 gene encoding the natural killer cell receptor, whose ligands are HLA-C molecules. Here, we found an association of HLA-C*05:01 allele with AD. KIR-HLA-C interactions are affected by peptides presented by HLA-C. The generation of these peptides is strongly influenced by endoplasmic reticulum aminopeptidases 1 and 2 (ERAP1 and ERAP2). Expression and activity of ERAP molecules depend on the polymorphisms of their genes. OBJECTIVE: Possible associations of several single nucleotide polymorphisms (SNPs) in the ERAP1 and ERAP2 genes with susceptibility to AD. METHODS: Peripheral blood DNA isolation from 318 patients and 549 controls. PCR-SSO or PCR-SSP for HLA-C typing; TaqMan Genotyping Assay for ERAP typing. RESULTS: Only one SNP in the ERAP1 gene, rs26618T>C, causing the amino acid change Ile276Met, had an association with AD. To gain insight on the functional role of this SNP, we produced recombinant variants differing only at position 276 (Ile or Met) and tested their aminopeptidase activity against a N-terminally extended precursor LIVDRPVTLV of the HLA-C*05:01 epitope IVDRPVTLV. Both ERAP1 variants were able to efficiently generate the epitope, although the 276Ile allotype was able to do this about 50% faster. Furthermore, both variants were quite inefficient in further degradation of the mature epitope. Finally, we found that the effect of 276Met on susceptibility to AD was seen only in KIR2DS1-negative individuals, not protected by this KIR. CONCLUSION: Associations of HLA-C*05:01 allele and rs26618T>C (Ile276Met) ERAP1 polymorphism with AD, and a significant difference between these two ERAP1 variants in their ability to generate an epitope for the HLA-C*05:01 molecule was found.

Children sustain high levels of skin DNA photodamage, with a modest increase of serum 25-hydroxyvitamin D3 , after a summer holiday in Northern Europe.

BACKGROUND: Childhood solar ultraviolet radiation (UVR) exposure increases the risk of skin cancer in adulthood, which is associated with mutations caused by UVR-induced cyclobutane pyrimidine dimers (CPD). Solar UVR is also the main source of vitamin D, essential for healthy bone development in children. OBJECTIVES: To assess the impact of a 12-day Baltic Sea (54° N) beach holiday on serum 25-hydroxyvitamin D3 [25(OH)D3 ] and CPD in 32 healthy Polish children (skin types I-IV). METHODS: Blood and urine were collected before and after the holiday and assessed for 25(OH)D3 and excreted CPD, respectively, and personal UVR exposure was measured. Diaries were used to record sunbathing, sunburn and sunscreen use. Before- and after-holiday skin redness and pigmentation were measured by reflectance spectroscopy. RESULTS: The average ± SD daily exposure UVR dose was 2·4 ± 1·5 standard erythema doses (SEDs), which is borderline erythemal. The mean concentration of 25(OH)D3 increased (× 1·24 ± 0·19) from 64·7 ± 13·3 to 79·3 ± 18·7 nmol L-1 (P < 0·001). Mean CPD increased 12·6 ± 10·0-fold from 26·9 ± 17·9 to 248·9 ± 113·4 fmol µmol-1 creatinine (P < 0·001). Increased 25(OH)D3 was accompanied by a very much greater increase in DNA damage associated with carcinogenic potential. Overall, skin type had no significant effects on behavioural, clinical or analytical outcomes, but skin types I/II had more CPD (unadjusted P = 0·0496) than skin types III/IV at the end of the holiday. CONCLUSIONS: Careful consideration must be given to the health outcomes of childhood solar exposure, and a much better understanding of the risk-benefit relationships of such exposure is required. Rigorous photoprotection is necessary for children, even in Northern Europe.

Alternative activation of hedgehog pathway induced by ultraviolet B radiation: preliminary study.

BACKGROUND: There is still much ambiguity in studies of Sonic hedgehog (Shh) pathways and its dysregulation. Some studies concerning the role of the Shh pathway in basal cell carcinoma (BCC) have been conducted, but there is a lack of studies about Shh pathway dysregulation under the influence of ultraviolet (UV)B radiation. AIM: To evaluate skin expression of Shh, Ptch1, Ptch2, Smo and Gli1 proteins in BCCs with and without the influence of UVB radiation. METHODS: In total, 34 healthy controls (HCs) and 42 patients with nodular BCC were recruited into the study. Patients were divided into five groups (A-E), depending on UVB dose received and BCC status. In all skin specimens, expression of Shh, Ptch1, Ptch2, Smo and Gli1 protein was evaluated. RESULTS: Comparing the BCC group with the HC group, there was significantly higher expression of Shh, Ptch1, Ptch2, Smo and Gli1 proteins. Expression of Ptch2, Smo and Gli1 was increased in response to UVB doses of 3 MED (minimal erythema dose), whereas expression of Ptch1 and Shh was unaffected. CONCLUSION: The lack of change in expression of Shh and Ptch1 after exposure to UVB suggests that the Shh pathway may be activated through a noncanonical pathway under the influence of strong UVB doses.

The A/A genotype of an interleukin-17A polymorphism predisposes to increased severity of atopic dermatitis and coexistence with asthma.

INTRODUCTION: Studies have found that the interleukin-23/T helper 17 (IL-23/Th17) pathway plays an important role in the pathogenesis of atopic dermatitis (AD). Inhibition of the IL-23/Th17 pathway with monoclonal antibodies reduces skin inflammation in animal models. AIM: To investigate the association between IL-17A and IL-23R gene single nucleotide polymorphisms (SNPs) and the development of AD in a Polish population. METHODS: Blood samples were collected from 166 patients with AD and 160 controls. We analyzed two SNPs, -152 G/A IL-17A and 1142 G/A IL-23R, using PCR and restriction fragment length polymorphism (RFLP) analysis. RESULTS: There was no statistically significant difference between the examined IL-17A SNP and the incidence of AD (P > 0.05 for all comparisons). Analysis of the IL-23R gene SNP showed no relationship between AD and the G/A genotype or presence of the A allele. The study did not establish any links between the IL-23R and IL-17A gene SNPs and the likelihood of developing AD resulting from gene-gene interaction. However, there was a significant relationship between the A/A genotype in the -152 G/A IL1-7A SNP and the coexistence of AD and asthma (P < 0.04). Analyzing the association between AD severity and the occurrence of IL-17A SNP, we found that subjects with the A/A genotype were at higher risk of developing moderate or severe AD (P = 0.02). CONCLUSIONS: We found no evidence of any effect of IL-17A or IL-23R SNPs on the occurrence of AD in our Polish population. However, the A/A genotype in IL-17A was found to predispose to increased AD severity and coexistence of AD and asthma.

The role of T-regulatory cells and Toll-like receptors 2 and 4 in atopic dermatitis.

Regulatory T cells (Tregs), toll-like receptors (TLRs) and interleukin-17 (IL-17) play important role in inflammatory diseases; however, their relevance in atopic dermatitis (AD) pathogenesis is not clear. The aim of study was to evaluate the number of circulating Tregs and peripheral blood mononuclear cells (PBMC) expressing TLR2 and TLR4 receptors in patients with AD. PBMC and CD4+/CD25(high) + Tregs were isolated from the whole blood of 32 AD patients and 36 healthy volunteers. Expression of CD4+CD25+, TLR2 and TLR4 receptors and IL 17+ was assessed with the flow cytometry. In the peripheral blood of AD patients, the percentage of Tregs was significantly higher when compared with the controls (P=0.0003). The number of TLR2+PBMC and TLR4+ PBMC in AD patients was significantly lower than in the controls (P=0.035; P=0.001, respectively). Also the percentages of Tregs with expression of both TLR2+ and TLR4+ in AD patients were significantly lower than in the control (3.85 versus 21.6, P<0.0001; 2.2 versus 17.6, P<0.0001, simultaneously). The percentage of CD4+/CD25high+/FOXP3+ Treg lymphocytes with expression of IL-17 was significantly higher in AD group than in healthy subjects (0.3% versus 0.06%; P=0.011). Distinct number of Tregs and various distribution of TLR2 and TLR4 expression on PBMC in AD patients suggest their contribution in the pathogenesis of AD.

Effect of chloroquine phosphate treatment on serum MMP-9 and TIMP-1 levels in patients with systemic lupus erythematosus.

Antimalarials are widely used for the treatment of systemic lupus erythematosus. However, their mechanisms of action have not been fully elucidated. Literature data indicate that matrix metalloproteinases may play a role in the immune response and tissue damage that occur in autoimmune skin diseases. The aim of this study was to determine the effect of 3 months of chloroquine treatment on serum levels of MMP-9 and TIMP-1 in patients with systemic lupus erythematosus. The study group consisted of 25 patients with systemic lupus erythematosus and 25 sex- and age-matched healthy volunteers. Before drug administration, serum levels of MMP-9 and TIMP-1 were determined by enzyme-linked immunosorbent assay. The same procedure was performed after chloroquine treatment. We found significantly higher median serum levels of MMP-9 in patients with systemic lupus erythematosus before therapy (57.20 ng/ml) when compared with controls (44.50 ng/ml) (p < 0.001). After chloroquine therapy the median MMP-9 serum level of systemic lupus erythematosus patients decreased significantly (43 ng/ml; p < 0.001). Before treatment the median TIMP-1 serum level in the patients with systemic lupus erythematosus was significantly higher than in the control group (500 vs. 200 ng/ml; p < 0.001), and after therapy it increased significantly (750 ng/ml TIMP-1; p < 0.001). The results suggest that chloroquine treatment may affect the matrix metalloproteinase network, and this effect may contribute to the immunoregulatory and anti-inflammatory properties of antimalarials.

Suberythemal ultraviolet B radiation alters the expression of cell cycle-related proteins in the epidermis of human subjects without leading to photoprotection.

BACKGROUND: Deregulation of the cell cycle proteins is one of the critical factors leading to cutaneous carcinogenesis. OBJECTIVES: To monitor the expression of cell cycle proteins in the epidermis of subjects after repeated exposure to ultraviolet (UV) B radiation, and to test for the development of photoprotection by subsequent irradiation with a single erythemal UVB dose. METHODS: A total of 26 healthy volunteers were divided into four groups: group 1 (n = 9) were given whole-body UVB irradiation for 10 consecutive days with 0.7 minimal erythema dose (MED), group 2 (n = 9) were irradiated as in group 1 followed 24 h later by a single UVB dose of 3 MED on buttock skin, group 3 (n = 4) were irradiated with a UVB dose of 3 MED on buttock skin, and group 4 (n = 4) were not irradiated. Skin biopsies were collected 24 h after the final irradiation and stained for cyclins A, B1, D1, and p16, p18, p21, p27, p53, pRB, Bax and Bcl-2. RESULTS: The expression of cyclin D1, p18 and p21 was significantly higher in groups 1 and 2 compared with the nonirradiated group 4 controls and, in group 2, the expression of pRB, p53 and Bax was also increased. In group 3, only p53 and Bax proteins were significantly elevated compared with group 4. The expression of cyclin D1, p16, p18, p27, pRB and Bcl-2 was higher in group 2 compared with group 3. CONCLUSIONS: Suberythemal UVB radiation was sufficient to cause changes in the expression of several epidermal cell cycle proteins. When tested by irradiation with a single erythemal UVB dose following the repeated exposures, no photoprotection against the UV-induced alteration in cell cycle protein expression was apparent.

Systematic administration of chloroquine in discoid lupus erythematosus reduces skin lesions via inhibition of angiogenesis.

BACKGROUND: Discoid lupus erythematosus (DLE) is a chronic cutaneous form of lupus erythematosus, characterized by inflammation and scarring skin lesions, with lymphocyte infiltration and vasodilation. Antimalarial drugs have beneficial therapeutic effects in DLE, partially resulting from their immunomodulating and photoprotective properties. The possible influence of these drugs on angiogenesis has not been previously evaluated. AIMS: To investigate the impact of chloroquine (CQ) treatment on the expression of vascular endothelial growth factor (VEGF, a major regulator of angiogenesis) and CD34 (a transmembrane glycoprotein expressed on endothelial cells and involved in tethering lymphocytes) in patients with DLE. METHODS: A 3-mm skin biopsy was taken from typical skin lesions in 10 people with DLE. Another biopsy was taken from the same area after 3 months of treatment with CQ (250 mg/day). Skin sections were stained with monoclonal antibodies directed against VEGF and CD34. The intensity of epidermal VEGF expression, and the number and area of CD34-positive dermal blood vessels were assessed. RESULTS: CQ treatment induced a reduction in epidermal VEGF expression. It also resulted in a significant decrease in the median number of CD34+ dermal blood vessels (from 219 to 125 vessels per mm(2)). Furthermore the median vessel area was significantly lowered from 9.76 x 10(6) to 6.92 x 10(6) mm(2) per mm(2) of the dermis. CONCLUSIONS: These results indicate that one beneficial effect of CQ treatment in DLE may be due to its antiangiogenic properties.

24 hour forecast of the surface UV for the antipsoriatic heliotherapy in Poland.

Analyses of the spectral and broad-band UV data collected at Belsk (20.79°E, 51.84°N), Poland, show that standard broad-band instrument, Solar Light (SL) 501A, could be used for measurements of both erythemal and antipsoriatic irradiance. A prognostic model is proposed for the next-day duration of outdoor exposure required to receive a dose, the so-called minimum antipsoriatic dose (MAD), equivalent to that received by standard antipsoriatic daily treatment in the phototherapy cabinet containing TL-01 fluorescent tubes. The model uses the 24 h forecast of the column amount of ozone (to predict next day clear sky UV irradiance), and low- and mid-level cloudiness (to estimate a reduction of the clear-sky UV irradiation due to clouds). The predicted duration of sunbathing required to receive a dose of 1 MAD matches the observed value, i.e. the correlation coefficients is 0.68. If the model predicts the antipsoriatic exposure over 1 MAD threshold the observed dose will be also above this threshold in 91% of cases. Thus, the model could be used for planning the next-day outdoor exposure to clear psoriasis. Hourly resolved maps, starting from 6 am up to 1 pm (GMT), showing the duration of antipsoriatic exposure over Poland are made public. The model provides a tool for a psoriatic patient to find the sunbathing starting time and its duration, which has the same healing potential as a single indoor phototherapy session.

Personal UVR exposure of farming families in four European countries.

BACKGROUND: The main risk factor for skin cancer is ultraviolet radiation (UVR). Farming families living in rural areas with easy outdoor access may experience excessive UVR exposure. Differences between countries in latitude, altitude and sun behaviour could result in different personal UVR exposures. However, no studies have examined this until now. OBJECTIVES: To determine personal UVR exposure in work and leisure situations among farming families in Europe. METHODS: Prospective cohort study of farmers, their partners (spouses) and children in Denmark (DK), Poland (PL), Austria (AT), and Spain (ES) from 2009 to 2011. Personal UVR exposure and sun behaviour were recorded by dosimetry and diaries. RESULTS: Farmers' average daily UVR exposure on working days ranged from 1.4 SED (DK, AT) to 2.7 SED (ES). Corresponding figures for partners were: 0.6 SED (DK) to 1.9 SED (PL), and for children (day-care/school days): 0.7 SED (ES) to 1.3 SED (PL). DISCUSSION AND CONCLUSIONS: Farmers' UVR exposure was comparable to that of outdoor workers in previous studies and exceeded the recommended UVR exposure limits on 36% (DK, AT), 29% (PL) and 56% (ES) of their working days. Attention to sun protection for outdoor workers across Europe in preventing UVR-induced skin cancer is still needed.

Perspectives of the antipsoriatic heliotherapy in Poland.

Statistical analysis of the daily course of exposures to TL-01 tube radiation for 93 psoriatic patients from the Medical University of Lódz during 20-day phototherapy shows that the dose of 1 J/cm(2) represents a unit of single exposure necessary for psoriasis healing. This value is converted to the antipsoriatic effective dose of 317.9 J/m(2) using the TL-01 lamp irradiance spectrum and the antipsoriatic action spectrum. It is proposed that the daily exposure of 317.9 J/m(2) serves as the standard antipsoriatic dose (SAPD) providing a link between the cabinet and the out-door exposures and it could be used for planning heliotherapy in Poland. A model is proposed to calculate ambient antipsoriatic doses for 3 h exposures around the local noon (9 am-12 am GMT) based on satellite measurements of ozone and cloud characteristics. The model constants are determined by a comparison with pertaining antipsoriatic doses measured by the Brewer spectrophotometer in central Poland. It is found that 3 h exposures to solar radiation in the period 15 May-15 September provides the mean (2005-2013) doses in the range 2.7-3.1 SAPD over Poland. Thus, heliotherapy could be treated as an alternative to the cabinet phototherapy for almost 4 months. It seems that the most effective site for antipsoriatic heliotherapy is the south/east part of Poland (the Bieszczady Mountains). The heliotherapy could be carried out in existing national health centers equipped with the standard easy-to-use biometers for on-line monitoring of UV level and controlling duration of sunbathing to avoid erythema risks. It is even possible to control the antipsoriatic heliotherapy by a patient himself, using low-cost hand-held instruments measuring UV index.

Space-based estimation of the solar UV-B doses for psoriasis heliotherapy in Poland using OMI data for the period 2005-2011.

A UV model is proposed to reconstruct the biologically weighted doses at the ground-level, erythemal, vitamin D(3), and antipsoriatic effective doses, based on the space data from the Ozone Monitoring Instrument on board of NASA EOS Aura spacecraft for the period 2005-2011. The model is training using the results of spectral UV measurements carried out at Belsk, Poland. The model outcome is verified using the UV spectra measured at Hradec Kralove, Czech Republic. The model uncertainty is almost the same for all examined action spectra and comparable to that found in earlier studies on differences between the satellite overpasses and ground-based erythemal data. Antipsoriatic doses, taken during 2h exposure periods near local noon, are reconstructed for selected sites in Poland to find if heliotherapy would be an alternative to standard treatment of psoriasis by tube irradiation in medical cabinets. Mountain-resort in the southern Poland, Zakopane, and rural-site in Central Poland, Belsk, are among the best location of potential heliotherapy centers in Poland for late spring/summer season. Leba, resort on the Baltic Sea coast, is a potential heliotherapy center in June and July. The methodology to disclose possible heliotherapy periods over the territory of Poland could be extended to any region. It would help to prepare an optimal schedule of antipsoriatic heliotherapy that accounts for local weather conditions and medical standards of using UV cabinets.

Effectiveness of heliotherapy for psoriasis clearance in low and mid-latitudinal regions: a theoretical approach.

The action spectrum for psoriasis clearance is reconstructed taking into account the results obtained in the early 1980s. The antipsoriatic action spectrum is used for weighting the medical cabinet UV spectra, and the solar spectra measured in San Diego (USA) and Belsk (Poland). The mean cumulative antipsoriatic effective dose of 450 mJ cm(-2), due to TL-01 (UVB narrowband) tubes, is taken by a patient with skin phototype II during routine 20 phototherapy sessions carried out in a phototherapy cabinet in the Medical University of Lódz. Thus, the daily mean dose of value 22.5 mJ cm(-2) is proposed as the threshold for daily solar dose for numbers of out-door exposures to clear psoriasis. We assume that the heliotherapy will last a whole month with every day 2h exposition to the direct sunlight around local noon. The heliotherapy will be successful if weather conditions permit at least 20 days with the daily exposure over the threshold. The minimum cumulative ambient erythemal dose, necessary for psoriasis clearance, is estimated as 144 standard erythema dose (SED) for the whole heliotherapy period. We find that heliotherapy could be effectively used in March through October (San Diego) and in June through August (Belsk). Thus, the heliotherapy against psoriasis is possible not only at southern resorts but even at the mid-latitude sites.

'2+1' Tricarbonyltechnetium(I) and -rhenium(I) mixed-ligand complexes with N-methylpyridine-2-carboxyamide and isocyanide or imidazole ligands-potential precursors of radiopharmaceuticals.

Complexes of tricarbonyltechnetium(I)-99m and rhenium(I)-188, of '2+1' type: with N-methylpyridine-2-carboxyamide as a neutral bidentate ligand and either tert-butyl 3-isocyanopropionate or imidazole as a monodentate ligand, have been obtained on n.c.a. level. The complexes exhibit moderate lipophilicity and rather high stability in neutral aqueous solutions. The latter has been evidenced from the tests on histidine/cysteine challenge and on protein binding in rat serum. The rhenium complexes studied are much more stable than their technetium analogues. The isocyanopropionate complex may be considered promising model for radiopharmaceutical precursors.

Acceptance of chronic illness in psoriasis vulgaris patients.

BACKGROUND: Acceptance of an illness is regarded as a considerable problem in patients with chronic diseases. Lack of acceptance can lead to lower adherence to medical treatment and delayed clinical improvement. Psoriasis, being a chronic skin disease, is known to cause considerable distress to patients. OBJECTIVES: To examine whether selected demographic factors and personal resources have an impact on acceptance of illness in psoriasis vulgaris patients. METHODS: Self-reported data on acceptance of illness, self-efficacy, health locus of control, optimism and coping strategies were collected from 100 psoriasis vulgaris inpatients and PASI was calculated by a dermatologist. The following measures were employed: acceptance of illness scale, generalized self-efficacy scale, multidimensional health locus of control scale, life orientation test and mental adjustment to disease scale. RESULTS: Physical factors such as sex, age, disease duration and severity, and family history of psoriasis had no effect on acceptance of illness. However, based on multiple regression analysis, higher levels of optimism, lower conviction of others' influence on one's health and the less frequently employed coping strategy concentration on emotions, together with more severe disease expressed by PASI, were correlated with higher acceptance of disease in psoriasis patients. CONCLUSIONS: The results obtained seem to confirm that personal resources play an important role in acceptance of chronic illness. Enhancement of optimism, and minimizing one's conviction that one's health depends on others could lead to higher acceptance of illness.

Chloroquine treatment reduces the number of cutaneous HLA-DR+ and CD1a+ cells in patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that can be exacerbated by exposure to ultraviolet radiation (UVR). The number and phenotype of antigen presenting cells in the skin play a role in cutaneous immune response generation. Although antimalarials are widely used in SLE treatment, their mode of action is not completely elucidated. The aim of our study was to determine the effect of chloroquine treatment on HLA-DR+ and CD1a+ cell number in locally irradiated (three minimal erythema doses of UVB) and normal appearing skin in SLE patients and healthy subjects. A significantly higher number of HLA-DR+ and CD1a+ cells were found in both locations in SLE patients compared with controls. Following three months of daily chloroquine treatment (250 mg), the HLA-DR+ and CD1a+ cell counts were significantly reduced in both irradiated and unirradiated sites of SLE patients, although still higher than in controls. Chloroquine treatment reduces the number of antigen presenting cells in the skin of SLE patients, and this effect may explain the antimalarials beneficial immunoregulatory and anti-inflammatory properties.

Repeated low-dose ultraviolet (UV) B exposures of humans induce limited photoprotection against the immune effects of erythemal UVB radiation.

BACKGROUND: Exposure of human subjects to ultraviolet (UV) B radiation causes immunosuppression. Most experiments to date have not tested the effects of low daily doses of UVB radiation. OBJECTIVES: To ascertain whether photoprotection against several UV-induced immune effects might develop following repeated exposure. METHODS: Groups of approximately 30 healthy individuals were given whole-body UVB irradiation on each of 10 consecutive days with 0.7 minimal erythema dose, or whole-body irradiation as before followed by a single erythemal UVB dose on a small body area, or irradiated only with a single erythemal UVB dose on a small body area, or were not irradiated. They were sensitized with diphenylcyclopropenone (DPCP) 24 h after the final dose, and skin biopsies collected to assess cytokine mRNA expression and the number of cells with thymine dimers and expression cyclooxygenase (COX)-1 and COX-2. RESULTS: The contact hypersensitivity (CHS) response to DPCP was significantly lower in the three irradiated groups compared with the unirradiated controls, while cutaneous interleukin (IL)-1beta, IL-6, IL-10 and tumour necrosis factor-alpha mRNAs, COX-1 and COX-2 and thymine dimers were all significantly higher. When the single erythemal UVB dose was given following the repeated low exposures, a slight downregulation in cytokine expression and thymine dimer formation was indicated. CONCLUSIONS: The repeated low doses of UVB protected to a limited extent against the effects of an erythemal UVB dose on cytokine expression and thymine dimer formation, but not on CHS or COX enzymes.

Long-term results of topical PUVA in necrobiosis lipoidica.

The aim of our study was to evaluate the long-term results of topical psoralen ultraviolet A (PUVA) in patients with necrobiosis lipoidica (NL), in whom conventional methods (pentoxifylline, vitamin E, tretinoin, and topical or intralesional corticosteroids) had failed. The study comprised 10 women (age range 17-44 years), six of whom were insulin-dependent diabetics and four were diabetes-free. Duration of NL ranged from 3 to 10 years. The patients were treated with a 0.005% aqueous solution of 8-methoxypsoralen, applied topically for 30 min, and subsequently irradiated with UVA three times weekly. All the patients experienced almost complete remission (softening of skin lesions, no hyperpigmentation, lack of lesion progression) after a mean of 47 sessions (mean UVA cumulative dose 69.5 J/cm2). They were followed up for 12-24 months, during which time two recurrences, both in diabetic patients, were observed after 8 and 12 months of treatment cessation, which further resolved after another course of topical PUVA. We conclude that topical PUVA is well tolerated by NL patients and may serve as an alternative therapeutic regimen.