Cutaneous tophi and calcinosis diagnosed in vivo by Raman spectroscopy.
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Adult↗
Biomedical subjects
H C Wulf
Publications and source records attributed to H C Wulf.
Autofluorescence of human skin is age-related after correction for skin pigmentation and redness.
When measuring the skin fluorescence in vivo, the absorption of chromophores such as melanin and hemoglobin often contribute predominantly to the changes in fluorescence and obscure the information from the fluorophores. We measured in vivo the collagen-linked 375 nm fluorescence (excitation: 330 nm) and 455 nm fluorescence (excitation: 370 nm) from nonexposed buttock skin of healthy volunteers. Skin pigmentation and redness of the same sites were quantified by reflectance of the skin at 555 nm and 660 nm. Multiple regression analysis was used to find the correlation between the fluorescence and skin pigmentation and redness. The fluorescence was corrected for the impact of pigmentation and redness according to the equation found in the regression analyses. The age-related trend of the fluorescence was evaluated. The 375 nm fluorescence showed positive relation to age, whereas the 455 nm fluorescence showed no significant relation to age. The increasing rate of the 375 nm fluorescence (logarithm transformed) was 2% per year, which is comparable with previously published data. The results suggest that the correction of the autofluorescence intensity for skin pigmentation and redness is valid, and the 375 nm skin autofluorescence may be used as a biologic marker of skin aging in vivo.
Adult↗
Differences in activation of G2/M checkpoint in keratinocytes after genotoxic stress induced by hydrogen peroxide and ultraviolet A radiation.
Long-wave ultraviolet radiation (UVA) may cause extensive DNA damage via reactive oxygen species (ROS). In this study we examined whether UVA- and H2O2-mediated DNA damage have equivalent effects on the induction of G2/M phase checkpoint and cell cycle progression in a transformed keratinocyte cell line HaCaT. By employing single cell gel electrophoresis (comet assay) we determined the equipotent doses of UVA and H2O2 with respect to the induction of alkali-labile sites (an indicator of oxidative DNA decay). However, in contrast to H2O2 which caused a pronounced G2/M cell cycle arrest 24 h after treatment, UVA irradiation did not affect cell cycle progression. Increasing UVA doses up to 150 kJ/m2 did not affect cell cycle and proliferation whereas increasing H2O2 concentrations caused a cell cycle block or cell death. Cytometric analysis revealed that G2/M cell cycle arrest took place beyond the cyclin B1 restriction point. We conclude that the DNA damage induced by UVA is easily repaired and does not perturb cell growth, whereas the H2O2-induced damage leads ultimately to cell cycle arrest or cell death.
Cell Division↗
Patients' perspectives on the burden of recurrent genital herpes.
The purpose of this study was to quantify the impact of recurrent genital herpes (RGH) on health-related quality of life, healthcare resource and workplace productivity. This was a cross-sectional survey conducted in 5 countries (Australia, Denmark, Italy, The Netherlands and UK). Patients with a confirmed history of RGH completed the MOS 36-Item Short Form Health Survey (SF-36) and the Recurrent Genital Herpes Quality of Life questionnaire (RGHQoL). Questionnaires addressing frequency of access to healthcare services and workplace productivity were also completed and patients' medical history was obtained. Scores for 6 of the 8 domains of the SF-36 were significantly lower (P<0.001) i.e. worse, compared with scores for the normal population. The RGHQoL score was significantly lower in patients experiencing more frequent or more severe recurrences. Forty-five per cent of patients estimated that their work effectiveness was reduced by between 25% and 50% due to genital herpes symptoms.
Adolescent↗
[Laser epilation. A systematic review of evidence-based clinical results].
Unwanted hair growth remains a therapeutic challenge and an effective treatment modality without side effects is needed. Today, hair removal is offered with lasers and light sources and patients may expect long-lasting or permanent hair removal. Evidence-based clinical results have been considerably examined for ruby and alexandrite lasers, whereas there is little documentation on Nd:YAG and diode lasers. The results with the diode laser are, however, promising. No controlled clinical studies have been published with intense pulsed light sources. We conclude that there is scientific evidence of a short-term effect after hair removal with ruby, alexandrite, Nd:YAG, and diode lasers (three, six months). Ruby and diode lasers may have a long-lasting effect (one year), but this, however, must be further clarified. No studies have examined whether laser hair removal may be permanent. The occurrence of postoperative side effects is reported to be low for all laser systems. From this review of the literature, we conclude that laser hair removal does not at the moment have a permanent or convincing long-lasting effectiveness.
Controlled Clinical Trials as Topic↗
[Why skin cancer?].
Basal cell carcinoma, squamous cell carcinoma, and malignant melanoma are the most prevalent types of skin cancer. Recent developments in skin cancer research have made it possible to identify environmental factors involved in cutaneous carcinogenesis and to describe the molecular pathology of skin cancer. The alterations in the sonic hedgehog signalling pathway are responsible for the development of basal cell carcinoma, whereas deactivation of the p53 protein is an important step in the pathogenesis of squamous cell carcinoma. The pathogenesis of malignant melanoma remains to be elucidated. This article reviews the current understanding of the carcinogenic role of ultraviolet radiation and briefly summarises the importance of other possible aetiological factors, such as oxidative stress, oncoviruses, diet, or immune suppression.
Carcinogens↗
Role of mitochondria in ultraviolet-induced oxidative stress.
The biological effects of ultraviolet radiation (UV), such as DNA damage, mutagenesis, cellular aging, and carcinogenesis, are in part mediated by reactive oxygen species (ROS). The major intracellular ROS intermediate is hydrogen peroxide, which is synthesized from superoxide anion ((*)O(2)(-)) and further metabolized into the highly reactive hydroxyl radical. In this study, we examined the involvement of mitochondria in the UV-induced H(2)O(2) accumulation in a keratinocyte cell line HaCaT. Respiratory chain blockers (cyanide-p-trifluoromethoxy-phenylhydrazone and oligomycin) and the complex II inhibitor (theonyltrifluoroacetone) prevented H(2)O(2) accumulation after UV. Antimycin A that inhibits electron flow from mitochondrial complex III to complex IV increased the UV-induced H(2)O(2) synthesis. The same effect was seen after incubation with rotenone, which blocks electron flow from NADH-reductase (complex I) to ubiquinone. UV irradiation did not affect mitochondrial transmembrane potential (DeltaPsi(m)). These data indicate that UV-induced ROS are produced at complex III via complex II (succinate-Q-reductase).
Cell Line↗
[Evidence-based ambulatory dermatological treatment].
The evidence base for routine therapeutic decisions in dermatological out-patients was studied in a random sample of the case-notes from 115 out-patients. The evidence base of therapy prescribed when the diagnosis was ascertained was studied in literature searches in MEDLINE and EMBASE. Evidence was structured into primary evidence consisting of randomised controlled trials, and secondary evidence consisting of follow-up studies or applying trial results from clinical analogies, e.g. atopic and seborrheic dermatitis treatment. Randomised controlled trials could be found describing 38% (95% confidence interval: 30-47) of all treatments. Secondary evidence was found for 33% (24-41), while no evidence was found for 23% (16-31) of the given treatments. Approximately 75% of dermatological out-patient therapy is founded on scientific evidence spanning from randomised controlled trials to logical deduction about a given disease from an analogous clinical situation. The proportion of evidence based medicine in dermatological therapy therefore appears comparable to that of other fields of medicine.
Adolescent↗
[Sunlight exposure and skin cancer].
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Basal Cell Carcinoma↗
Photodynamic therapy with 5-aminolaevulinic acid or placebo for recalcitrant foot and hand warts: randomised double-blind trial.
BACKGROUND: Photodynamic therapy (PDT) with topical 5-aminolaevulinic acid (ALA) followed by irradiation with incoherent light (ALA-PDT) for recalcitrant warts have had beneficial results. Therefore, we undertook a randomised, parallel, double-blind clinical trial of ALA-PDT versus placeboPDT for recalcitrant foot and hand warts. METHODS: Recalcitrant foot and hand warts were randomly assigned to six repetitive ALA-PDT or placebo-PDT interventions combined with standard treatment encompassing paring followed by a keratolytic (Verucid). Standardised photographs of each wart were taken before, during (week 7) and after treatment (weeks 14 and 18). The area of each wart compared with entry area was the primary outcome variable, measured from photographs by an evaluator unaware of treatment allocation for intervention. Pain intensity immediately and 24 h after each intervention was assessed by a five-point scale. FINDINGS: A total of 232 foot and hand warts in 45 patients were entered into the trial: 117 warts were allocated to ALA-PDT and 115 warts to placebo-PDT. In week 14, the median relative reduction in wart area was 98% in the ALA-PDT group (interquartile range 100%, 55%) versus 52% (100%, 0) in the placebo group (p=0.0006). In week 18, the median relative reduction in wart area was 100% in the ALA-PDT group (100%, 57%) versus 71% (100%, 0) in the placebo-PDT arm (p=0.008). Both the number of vanishing warts and the difference in relative wart area of persisting warts at week 14 and 18 were significant (p<0.05) in favour of ALA-PDT. Significantly more ALA-PDT warts were graded at a higher pain intensity after treatment than placebo-PDT warts. INTERPRETATION: ALA-PDT is superior to placebo-PDT when both wart area and number of vanishing warts are considered.
Adult↗
Laser scanning cytometry for comet assay analysis.
BACKGROUND: The comet assay (single-cell gel electrophoresis) is a sensitive method for evaluating nuclear DNA damage. Previously used evaluation methods for the comet assay are time consuming and have an inherent risk of biased selection of comets due to manual selection and categorization of comet images. Laser scanning cytometry (LSC), the principle of which is equivalent to flow cytometry, enables quantification of fluorescence emitted from the cells on a microscope slide. In the present study, we explored whether LSC could be used to determine the degree of DNA damage demonstrated by the comet assay. METHODS: DNA damage was induced by ultraviolet A irradiation of keratinocytes and visualized by the comet assay. The evaluation included (a) LSC determination of DNA-specific fluorescence in 1,000 comet heads (undamaged DNA), (b) image acquisition of comets by rescanning of the microscope slide, and (c) digital image analysis and computation of tail moment and DNA content in the comet tails. RESULTS: Cells with damaged DNA were observed in a sub-G(1) area because the comet head loses DNA to the tail. We found a strong inverse correlation between tail moment and DNA content per nucleus. CONCLUSIONS: LSC enables an automated method for cell recognition and evaluation of the comets, thus providing quantitative information about nuclear DNA damage without subjective selection of analyzed comets.
Cells, Cultured↗
Hydrogen peroxide is responsible for UVA-induced DNA damage measured by alkaline comet assay in HaCaT keratinocytes.
We investigated the role of different reactive oxygen species (ROS) in ultraviolet A (UVA)-induced DNA damage in a human keratinocyte cell line, HaCaT. UVA irradiation increased the intracellular levels of hydrogen peroxide (H2O2), detected by a fluorescent probe carboxydichlorodihydrofluorescein, and caused oxidative DNA damage, single strand-breaks and alkali-labile sites, measured by alkaline single cell gel electrophoresis (comet assay). Superoxide anion (O2*-) was a likely substrate for H2O2 production since diethyldithiocarbamate (DDC), a superoxide dismutase blocker, decreased the level of intracellular H2O2. Hydrogen peroxide was shown to play a central role in DNA damage. Increasing the intracellular levels of H2O2 with aminotriazole (AT) (a catalase blocker) and buthionine sulfoximine (BSO) (an inhibitor of glutathione synthesis) potentiated the UVA-induced DNA damage. Exogenous H2O2 was also able to induce DNA damage. Since H2O2 alone is not able to damage DNA directly, we investigated the significance of the H2O2-derived hydroxyl radical (*OH). Addition of FeSO4, that stimulates *OH formation from H2O2 (Fenton reaction) resulted in a twofold increase of DNA-damage. Desferrioxamine, an iron chelator that blocks the Fenton reaction, prevented UVA-induced DNA damage. We also employed a panel of less specific antioxidants and enzyme modulators. Sodium selenite (Na-Se) present in glutathione peroxidase and thioredoxin reductase and addition of glutathione (GSH) prevented DNA-damage. Tocopherol potently prevented UVA-and H2O2-induced DNA damage and reduced intracellular H2O2 -levels. Ascorbic acid reduced H2O2 production, but only partly prevented DNA damage. Singlet oxygen (1O2) did not seem to play an important role in the UVA-induced DNA-damage since the specific 1O2 scavenger sodium azide (NaN3) and the less specific 1O2 scavenger beta-carotene did not markedly prevent either DNA-damage or H2O2 production. In conclusion the conversion of H2O2 to *OH appears to be the most important step in UVA-induced generation of strand breaks and alkali-labile sites and the bulk H2O2 appears to originate from O2*- generated by UVA irradiation.
Cell Line↗
The wrist is a reliable body site for personal dosimetry of ultraviolet radiation.
The purpose of this study was to investigate the reliability of measuring solar ultraviolet radiation (UVR) doses with personal UV dosimeters worn on the wrist. Individual solar UVR exposure was measured over one day under standardised conditions (One-day Beach Study), and over an extended period of time with varying UV exposure and activities (Holiday Study). Dosimeters of a UV-sensitive spore-film filter type (VioSpor) were placed on the right wrist and on the top of head of the test subjects. The wrist was chosen as being a practical position for personal dosimetry and the head position as an internal control for maximal personal UV doses. The One-day Beach Study took place in the vicinity of Copenhagen in June 1998 over 5 h and included 11 subjects. The Holiday Study included 9 subjects during a period with a mean of 14 days in Scandinavia and Europe from June to September 1998. The head position received the highest UV dose in all subjects in both studies. In both studies, despite considerable individual variation, the mean wrist dose was the same (50%) of that received on the head, although the wrist dose correlated significantly with head dose (P<0.01) only in the Holiday Study. We conclude that the wrist position is a practical and convenient body site for personal dosimetry, yielding reliable results in group exposure studies.
Adult↗
Optimized UVB treatment of psoriasis: a controlled, left-right comparison trial.
In a randomized, controlled, left-right comparison study, 20 patients with chronic plaque psoriasis were treated with UVB. One side of the body received UVB in a conventional regimen with fixed dose increments, the other side was given UVB doses according to measurements of skin pigmentation. Skin pigmentation was quantified by the skin reflectance technique. The relationship between skin pigmentation and sensitivity to UV radiation was used to optimize and individualize the initial UVB exposure dose. Clinical outcome, initial, final and cumulative UVB doses, time to 50% reduction in PASI score, and side-effects were compared. The consequence of the optimization of the UVB doses with a skin reflectance meter was that the initial UVB dose was significantly higher than in the conventional UVB regimen. PASI scoring demonstrated a more rapid improvement during the first 2 weeks of treatment on the half body receiving the optimized treatment compared to the other side (P < 0.05). This new technique offers the same therapeutical advantages and security as a dose regimen guided by minimal erythema dose testing. However, measurement of skin pigmentation by skin reflectance is a quick method which can be operated easily by nurses.
Adult↗
Resistance of senescent keratinocytes to UV-induced apoptosis.
Irradiation with ultraviolet (UV) triggers programmed cell death (apoptosis) in keratinocytes. This process is believed to protect against skin carcinogenesis since the cells with damaged DNA are selectively removed, limiting the likelihood of the development of a malignant keratinocyte clone. The p53 protein is able to detect mutation-bearing DNA fragments and is thus indispensable for the UV-induced apoptosis in the epidermis. Since age is a risk factor for the development of skin tumors we investigated whether ultraviolet induces apoptosis and p53 activation in senescent keratinocytes. Cultured senescent keratinocytes were irradiated with broad-band ultraviolet, apoptosis was assessed using TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling) technique and the p53 activation pattern was determined with Western blotting and immunofluorescent staining with a panel of anti-p53 antibodies recognising different conformational forms of the protein (PAb 122, PAb 240, DO-7). In senescent keratinocytes arrested in the G1 phase of cell cycle, ultraviolet irradiation (100-2000 J/m2) caused accumulation and nuclear translocation of p53. However, in contrast to young cells where UV induces apoptotic cell death in G1, apoptosis was not detected in senescent cells. There were subtle differences in the p53 activation pattern between senescent keratinocytes and known patterns in young keratinocytes and other cell types. In senescent keratinocytes a constitutional nuclear expression of p53 (conformational form recognized by PAb 240) was present and the p53 induction in response to ultraviolet radiation was rapid. Suppression of apoptosis in senescent keratinocytes may be an important mechanism responsible for enhanced skin carcinogenesis in old age.
Antibodies, Monoclonal↗
Hydration of human nails investigated by NIR-FT-Raman spectroscopy.
The human nail, although it is usually stable against outer influences, becomes soft and flexible after soaking in water. Frequent washing increases brittleness of nails. Hydration of nails is thought to be the most important factor influencing the physical properties of nails and possibly acts through changes in keratin structure. Here NIR-FT-Raman has been used to examine molecular structural changes of intact moisten nails. Raman spectra were obtained both in vitro from nail samples and in vivo before and after soaking in water. The water uptake of normal nail samples during the first 15 min was reflected in the increasing intensity ratio of the nu(OH)/nu(CH(2)) bands. A saturating effect appeared soon after 10 min which is explained by a defined water holding capacity. R(nu) representation of the low frequency range of the Raman spectra showed that mainly bound water is found both in dry and in wet nails. This implies water-protein interaction. Protein backbone vibration at 932 cm(-1) indicating alpha-helical proteins increased in intensity in the wet nails. The nu(S-S) which is sensitive to changes in conformation of proteins showed a 4% higher intensity. Additional protein-water interactions could lead to a slight change of the dihedral angle of the C-S-S-C bonds and to geometric changes in coiling behavior of the alpha-helical protein. Suggesting a separation between matrix proteins and fiber proteins giving them a greater freedom of flexibility. The in vivo spectra detected from the distal part of the nail resembled spectra in vitro. Raman spectra of the proximal part of the nail showed that it was fully saturated with water. The proximal part of the nail did not show changes in water content and protein structure during nail moisturizing in the Raman spectra. Our results suggest that the softening of the nail following hydration may be due to changed matrix protein molecular structure induced by water.
Humans↗
Isomerization of urocanic acid after ultraviolet radiation is influenced by skin pigmentation.
Exposure to ultraviolet (UV) radiation may induce erythema, DNA damage and suppression of immune responses. Melanin pigmentation offers protection against the first two of these effects, but immunosuppression seems to occur irrespective of the subject's pigmentation. Cis-urocanic acid (cis-UCA), produced by isomerization of trans-UCA in the stratum corneum on UV exposure, initiates some of the immunomodulatory effects of UV radiation. In the present study the relationship between skin pigmentation and UCA isomerization has been examined in 28 healthy individuals of skin types I-IV. Pigmentation is measured in five areas of not recently exposed back skin before irradiation with 0, 0.45, 0.9, 1.8 and 3.6 standard erythema dose (SED) of filtered broadband UV-B (1 SED = 10 mJ cm-2 at 298 nm). The concentration of UCA isomers is measured immediately after the irradiation. With 3.6 SED, the relative production of cis-UCA is close to the maximum obtainable, irrespective of skin type. A significant negative correlation is found between pigmentation and relative production of cis-UCA at 0.45 and 1.8 SED, and between pigmentation and absolute production of cis-UCA at 0.45 SED. At doses of 0.45 and 0.9 SED the relative and absolute production of cis-UCA are higher in the group with skin types I and II when compared with the group with skin types III and IV. The higher isomerization in the lightly pigmented subjects than in the more pigmented ones may indicate that people with fair skin are at a relatively higher risk of immunosuppression when exposed to low doses of UV radiation.
Adolescent↗
Recalcitrant hand and foot warts successfully treated with photodynamic therapy with topical 5-aminolaevulinic acid: a pilot study.
The purpose of this pilot study was to determine if photodynamic therapy with topical application of 5-aminolaevulinic acid followed by irradiation with incoherent filtered and unfiltered light (ALA-PDT) is an effective therapy for recalcitrant hand and foot warts. In 30 patients with recalcitrant warts, 49 regions with a total of 250 warts were randomized to one of the following five treatments: (i) ALA-PDT with white light applied three times within 10 days (W3); (ii) ALA-PDT with white light applied once (W1); (iii) ALA-PDT with red light applied three times within 10 days (R3); (iv) ALA-PDT with blue light applied three times within 10 days (B3), and (v) cryotherapy applied up to four times within 2 months (CRYO). The ALA-PDT treatment modality was repeated in case of partially responding warts. Significantly more warts were completely healed after W3 and W1 than after R3, B3 and CRYO (P < 0.01): 73% of the warts treated with W3 were completely healed, 71% after W1, 42% after R3, 23% after B3 and 20% after CRYO. No scars were observed in the ALA-PDT treated areas and patients treated for foot warts were all able to walk after the treatment. No recurrences in completely responding ALA-PDT treated warts were observed after 12 months of follow-up. In conclusion, photodynamic therapy with topical 5-aminolaevulinic acid followed by irradiation with white light is a promising treatment for recalcitrant hand and foot warts.
Administration, Topical↗