Structure-activity relationships in allergic contact dermatitis

Primin (2-methoxy-6-pentyl-1,4-benzoquinone)is a naturally-occurring strong sensitizer from Primula obconica (Primulaceae), To determine the effect of side-chain length on senstizing potency 15 analogues with linear side chains from to from C₁, to C₁₅ and 4 C₆- analogues with branched side chains were prepared synthetically and devoted to experimental sensitization in guinea pigs The results showed an increase of the sensitizing capacity with increasing length of the alkyl side chain from C₁ to C₁₀, reaching a maximum at C₁₁ and C₁₂. On further elongation the senstizing potency decreased beyond C₁₃ reaching values which finally were as low as those of the C₁ and C₃ derivatives. The results mirror finding which finally were as low as those of the C₁ and C₃ derivatives. The results mirror findings which formerly have been obtained with other non-quinonoid compounds like catechols, phenols hydroquinones and gallates. In the plant kingdom. Compound approximating an "ideal allergen" consisting of a quinonoid ring with a 10 or 11 carbon-remarkably strong sensitizer found in Wigandia caracasana (Hydrophyllaceae)     

A case of contact dermatitis due to impurities of cetyl alcohol

A 29-year-old man being treated for itchy lesions on the amputation stump of the thigh became allergic to betamethasone valerate and gentamicin sulfate cream (Rinderon VG®. Closed patch tests with all the ingredients of the cream revealed positive reactions to cetyl alcohol 30% to 5% pet. Gas chromatographic analysis of the cetyl alcohol in the cream base detected stearyl alcohol (C₁₈), myristyl alcohol (C₁₄) and lauryl alcohol (C₁₂) in addition to the main component of cetyl alcohol (C₁₆). Patch testing with 99% pure analytical reagent grade saturated alcohols. (C₁₀, C₁₁, C₁₂, C₁₃, C₁₄, C₁₅, C₁₆, C₁₇, C₁₈, C₁₉, C₂₀) showed negative reactions. Thus, it is concluded that some minor impurities in cetyl alcohol not detected by gas chromatography might be the cause of this dermatitis.     

Cytokeratins in human basal and squamous cell carcinomas: biochemical, immunohistological findings and comparisons with normal epithelia

The nature of epithelial cell cytokeratins from epidermal basal cell carcinomas (BCC) (8 cases) and squamous cell carcinomas (SCC) (5 cases) was investigated by biochemical and immunological analysis. Cytokeratin proteins were extracted with high salt buffer and triton X 100 and were comparatively analyzed by SDS (sodium dodecyl sulphate) polyacrylamide gel electrophoresis. Both types of tumor showed either an absence or a very low amount (5% of the total protein) of the major protein band (MW 67000) present in normal human epidermis. This correlated well with results of immunolabelling showing that 67000 keratin antisera, only reacted with some dyskeratotic cells in sections of these tumors. Gel electrophoresis showed in BCC and SCC, three distinct groups of predominant polypeptide bands of apparent relative MW: (1) 60–62000 (2) 54–56000 and (3) 49000, representing respectively about 43.0%, 31.0% and 20.4% of the total proteins.
Antibodies raised in animals against polypeptide bands C₁ (MW 62000), C₂ (MW 56000) and C₃ (MW 49000) from SCC, strongly labelled (indirect immunofluorescence) all malignant cells present in the 2 kinds of tumors. These antisera showed a preferential reaction with the basal epithelial cells, in sections of human and animal epidermis and mucosa thus, suggesting numerous common antigenic determinants between epithelial cells from diverse origins. On the other hand, strong differences between mucosal and epidermal upper layers were noted with C₁ C₂, C₃, and 67000 antisera. These results are further evidence for the existence of different pathways of keratinization in epidermis and mucosa.     

Complement Components in Recurrent Genital Herpes Simplex

ABSTRACT: Complement components 1,2,3,4 and total complement hemolytical activity CH₅₀ were studied in 39 patients with serve recurrent genital herpes simplex. The results show statistically significant and selective diminution of C₄ (P>0.001) The other components were normal. C₄ has a specific action against herpesvirus by itself or associated to some other elements over C₄ failure, local or systemic disturbances alter the homeostasis of specific and nonspecific immune system, provking a disbalance host-virus which would explain the recurrence.     

Induction of apoptosis by synthetic ceramide analogues in the human keratinocyte cell line HaCaT

Abstract: In contrast to extracellular, long chain ceramides which comprise a structural component of the epidermal water barrier, intracellular ceramides originating from sphingomyelin hydrolysis have been shown to inhibit proliferation and to induce apoptosis in different cell populations. To further elucidate the possible role of intracellular ceramides in human epidermis, two new cell-permeable ceramide analogues, N -thioacetylsphingosine (C₂-Cer=S) and 4-dodecanoylamino-decan-5-ol (FS-5), were synthesized and tested for their ability to suppress cell growth and to induce apoptosis in immortalized human keratinocytes. It was shown that the well-investigated ceramide analogue N -acetylsphingosine (C₂-Cer=O), as well as the new compound C₂-Cer=S inhibited proliferation of HaCaT cells with half-inhibitory concentrations (IC₅₀) of 20 μg/ml and 10 μg/ml, respectively, whereas FS-5 has been potent with an IC₅₀>40 μg/ml. Overall, all three ceramide analogues induced apoptosis in HaCaT cells as assessed by DNA-fragmentation using ELISA technique and in situ nick end labelling, thereby confirming the importance of ceramide signalling in keratinocytes.     

Conjunctival involvement in the autoimmune blistering dermatoses: a clinical and histopathological study

The conjunctiva was examined by slit lamp microscopy and biopsy for direct immunofluorescence (IF) in patients with cicatricial pemphigoid (CP), bullous pemphigoid (BP), pemphigoid gestationes (PG), linear IgA dermatosis (LAD), pemphigus and dermatitis herpetiformis (DH).
In CP, five of 13 patients had definite scarring, seven equivocal, and one no signs. IF showed linear deposition of IgG and/or C₃ along the BMZ in 45%.
In BP, six of 18 patients had fine conjunctival scarring. IF showed linear IgG IgA and/or C₃ in 73 %. Scarring was not observed in one PG patient.
In LAD, three of seven patients had conjunctival scarring, one with marked symblepharon. IF in five patients showed linear IgG without IgA in three.
In pemphigus, neither of two patients had scarring. IF in both showed IgG and/or C3 between epithelial cells.
In DH, one of three patients had fine scarring.
These findings demonstrate that conjunctival involvement may occur in autoimmune bullous dermatoses other than CP and LAD.     

Pemphigus vegetans of Hallopeau following pemphigus foliaceus

A 69-year-old woman previously affected with pemphigus foliaceus developed pustular lesions followed by verrucous vegetations, localized in the left sub-mammary fold. Histological examination of vegetating lesions showed consistent acanthosis and papillomatosis with intraepidermal microabscesses containing eosinophils. Direct immunofluorescent examination evidenced intraepithelial IgG and C₃ deposits. Circulating pemphigus antibodies were positive at titre 1: 160. This case suggests a clinical link between pemphigus vegetans and pemphigus foliaceus.     

Skin application of the nonsteroidal anti-inflammatory drug ketoprofen downmodulates the antigen-presenting ability of Langerhans cells in mice

Background  Ketoprofen (KP) is widely used as a topical nonsteroidal anti-inflammatory drug that inhibits prostaglandin (PG) biosynthesis. As PGE₂ upregulates the antigen-presenting activity of Langerhans cells (LCs), i.e. migration to lymph nodes and expression of immunocompetent molecules, modulation of LC functions resulting from topical application of KP is an issue to be clarified.
Objectives  To investigate the in vivo effect of KP application to the skin and the in vitro effect of KP addition to the culture on the antigen-presenting ability of murine LCs.
Methods  Ears of BALB/c mice were painted with picryl chloride (PCl) hapten, KP or both. An immunofluorescence study of epidermal sheets and a flow cytometric analysis of epidermal cell suspensions from the treated ears were performed.
Results  PCl altered the morphology of LCs and reduced their number, and simultaneous application of 10% KP maintained LC morphology and number. KP at 5% or 10% clearly decreased the PCl-augmented expression of major histocompatibility complex class II and CD86 on LCs. In cultivation of freshly isolated epidermal cells, 5 mmol L⁻¹ KP inhibited the culture-promoted expression of these molecules on LCs, whereas 100 μmol L⁻¹ indomethacin was not inhibitory. The further addition of PGE₂ to the KP-containing epidermal cell culture did not restore the expression of these molecules. Moreover, topical application of 10% KP to the sensitizing sites suppressed the development of contact hypersensitivity to PCl.
Conclusions  KP may have the potential to inhibit the antigen-presenting ability of LCs, in a PGE₂-independent manner.     

Prostanoid receptors in anagen human hair follicles

Abstract:  Prostanoid pathway in hair follicle gained closer attention since trichogenic side-effects on hair growth has been observed concomitantly with prostaglandin F_2α receptor (FP) agonist treatment of intraocular pressure. We thus investigated prostanoid receptor distribution in anagen hair follicle and different cell types from hair and skin. Using RT-PCR, Western blot and immunohistochemistry (IHC), we found that all receptors were present in hair follicle. This data shed new light on an underestimated complex network involved in hair growth control. Indeed most of these receptors showed a wide spectrum of expression in cultured cells and the whole hair follicle. Using IHC, we observed that expression of prostaglandin E₂ receptors (EP₂, EP₃, EP₄), prostaglandin D₂ receptor (DP₂), prostanoid thromboxane A₂ receptor (TP) and to a lesser extent EP₁ involved several hair follicle compartments. On the opposite, Prostaglandin I₂ receptor (IP) and DP₁ were more specifically expressed in hair cuticle layer and outer root sheath (ORS) basal layer, respectively. FP expression was essentially restricted to ORS companion layer and dermal papilla ( DP ). Although extracting a clear functional significance from this intricate network remains open challenge, FP labelling, i.e. could explain the biological effect of PGF_{2 α} on hair regrowth, by directly modulating DP function.     

Sodium tetrachloropalladate (Na2[PdCl4]) as an improved test salt for palladium allergy patch testing

Background:  In the last decades, palladium is widely used in dentistry. Allergic reactions to palladium are rarely diagnosed with patch testing, even when positive results would be expected. Palladium tends to cross-react with nickel, which should give rise to more positive reactions to palladium dichloride (standard test salt).
Objective:  The aim of the study was to test whether or not mono-nuclear sodium tetrachloropalladate (Na₂[PdCl₄]) in petrolatum is a better test salt for diagnosing palladium allergy. Positive reactions to the investigated test salt are compared not only with PdCl_2(aq.), but also to NiSO_4(aq.) and NiSO_4(pet.).
Patients/Methods:  Concentration series of Na₂[PdCl₄] were carried out. 164 consecutive patients were patch tested.
Results:  3% of Na₂[PdCl₄]_(pet.) was found to be the highest non-irritative concentration. The results show ( n  = 164) that Na₂[PdCl₄] covers all reactions to PdCl₂ (1.8%) and provokes more positive reactions (14%). From the 164 patients, 18.3% reacted positively to at least 1 of the nickel salts.
Conclusion:  The sensitivity of patch testing with Na₂[PdCl₄] is increased compared with the PdCl₂ salt. Therefore, it can be concluded that Na₂[PdCl₄] is to be a better test salt for diagnosing palladium allergy with patch testing.     

The intradermal effects of the H3 receptor agonist R α methylhistamine in human skin

We have investigated the possible existence of the H₃ histamine receptor in human skin with the highly selective ligands R α methylhistamine (RAMHA) (H₃ agonist) and thioperamide (H₃ antagonist). We compared the intradermal effects of RAMHA with histamine, and studied their potential modulation by the H₁ antagonist terfenadine, and H₂ antagonist cimetidine. The effects of RAMHA and thioperamide on codeine phosphate-, substance P- and histamine-induced weal and flare responses were also studied. RAMHA produced dose-related weal and flare responses that were approximately 10- and fivefold less, respectively, than responses to histamine. Flare responses to RAMHA were significantly inhibited by oral terfenadine ( P  < 0.05). Weal and flare responses to histamine after oral cimetidine showed much intersubject variation, and cimetidine did not significantly alter either RAMHA- or histamine-induced weal and flare responses. Codeine phosphate-, substance P- and histamine-induced responses were not significantly affected by concurrent administration of RAMHA. Thioperamide was not found to influence codeine phosphate-, substance P-, RAMHA- or histamine-induced effects. RAMHA induces vascular (weal and flare) responses in human skin, and these responses are partially inhibited by terfenadine. There is a trend for RAMHA to have an additive effect to the weal induced by substance P and histamine, although our results largely do not reach statistical significance. Thioperamide does not affect the vascular responses to RAMHA, codeine phosphate, histamine or substance P. We cannot conclude that the effects of RAMHA are induced by H₃ receptors on cutaneous endothelial or mast cells.     

1α,24-Dihydroxyvitamin D3 (tacalcitol) is effective against Hailey–Hailey disease both in vivo and in vitro

We report a case of Hailey–Hailey disease (HHD) in which 1α,24-dihydroxyvitamin D₃ (tacalcitol) was effective both clinically ( in vivo ) and in explant cultures ( in vitro ) of a skin lesion. The patient was a 65-year-old man with HHD lesions in the axillary and inguinal areas bilaterally. We applied ointment containing 1α,24-dihydroxyvitamin D₃ (tacalcitol), an analogue of active vitamin D₃, to the lesions and assessed its clinical effectiveness. The HHD lesions in both groins disappeared after treatment with the 1α,24-dihydroxyvitamin D₃ ointment, and the remission has continued to the present. A punch biopsy specimen of the lesion that had remitted showed no acantholysis. In addition, dissociation of migrating keratinocytes was observed when biopsy specimens of the HHD skin lesion were cultured in medium without 1α,24-dihydroxyvitamin D₃, but inhibition of keratinocyte dissociation was observed in medium containing it. These results suggest the effectiveness of 1α,24-dihydroxyvitamin D₃ against HHD both in vivo and in vitro .     

Dietary factors and the risk of psoriasis. Results of an Italian case–control study

Summary We have conducted a case-control study to explore the relation between the consumption of selected foods and psoriasis. The out-patient services of nine teaching hospitals and five general hospitals in northern and southern Italy took part. Cases were newly diagnosed psoriatics with a history of skin problems of no more than 2 years. As controls. we selected subjects with newly diagnosed skin conditions, other than psoriasis, who were seen in the same out-patient clinics. Inclusion of cases and controls was limited to the age group 16–65 years. A total of 316 psoriatics and 366 controls were recruited. Anthropomentric measures, including height and weight, were obtained. Diet was assessed by a semiquantitative food frequency questionnaire. Psoriasis appeared to be positively associated with body mass index (X²₁ trend 4.3, P < 0.05). Significant inverse relations with psoriasis were also observed for the intake of carrots (X²₁ trend 4.8, P < 0.05), tomatoes (X²₁ trend 26.3, P < 0.01), fresh fruit (X²₁ trend 11.7, P < 0.01) and index of beta-carotene intake (X²₁ trend 9.1, P < 0.01). Although largely explorative, these results provide some evidence for a potential role of diet in psoriasis.     

Interaction of metals in nickel-sensitive patients

Nickel (Ni) dermatitis is, thought to involve the formation of complexes between Ni ions and suitable proteins. 4 groups of 30 subjects who gave positive patch test responses to NiSO₄ 2.9% aq. were each retested to 1 of 4 different solutions containing equimolar (0.1 M) amounts of NiSO₄ plus MgSO₄. NiSO₄ plus CuSO₄, NiSO₄plus ZnSO₄. and NiSO₄ plus Li₂SO₄, respectively. The results, evaluated at 2 days by visual scoring only, demonstrated that the 4 metals exerted a different influence on the nickel reactions, perhaps interfering with one or more factors affecting the formation of Ni++ complexes.     

A comparison of erythema efficacy of ultraviolet B irradiation from Philips TL12 and TL01 lamps

The erythema efficacy of UVB irradiation from Philips TL12 and TL01 lamps has been evaluated and compared. Thirty-seven healthy Thai volunteers were irradiated on the previously unexposed lower back with TL12 and TL01 lamps in doses ranging 100 to 550 mJ/cm² and 360 to 2020 mJ/cm², respectively. Erythema was evaluated clinically and measured by a narrow-band spectrophotometer before exposure and 24 h after exposure. The threshold doses of UVB that induced barely perceptible erythema (MED_b) with well-defined border erythema (MED_w) and the steepness of the dose-response curves for erythema (DRAE) were compared. We found that MED_b and MED_w of the TL01 lamps were 4.19 and 4.52 times those of TL12 lamps, which were similar to those calculated from the CIE erythema action spectrum (4.2). However, the DRAE of the two lamps were quite similar. Because the initial dosage of UVB phototherapy is usually given as a percentage of a patient's MED, the initial exposure of TL01-UVB phototherapy should be about 4.2 times that of TL12-UVB.     

THE VITAMIN B12 LEVEL IN PSORIATIC SKIN AND SERUM

SUMMARY.— Skin and serum B:; levels were measured using Lactobacillus leishmanii in 16 non-psoriatic control subjects and in 10 psoriatic patients before and after treatment. There was a significant positive correlation between the B₁₂ levels of the skin and serum of the control group. The B₁₂ level was lower in psoriatic than non-psoriatic skin and active lesions had lower levels than healed lesions. The findings suggest that the increased metabolic activity in psoriatic skin is associated with lowered B₁₂ levels which may precede visible pathological change.     

SULPHATED ACID MUCOPOLYSACCHARIDES IN ACTINIC ELASTOSIS

SUMMARY.— The incorporation of ³⁵SO₄ into the acid mucopolysaccharides of skin in vitro has been used to study the metabolism of these substances in skin showing gross actinic elastosis, in exposed skin with less severe actinic changes, and in non-exposed skin.
Whereas no alteration in the pattern of incorporation was demonstrated in the epidermis, elastotic dermis showed an increased incorporation of ³⁵SO₄, especially into the chondroitin-6-sulphate peak, as compared to the non-exposed dermis. The possible biological implications of these results are discussed, namely, (a) that treatment with weak alkali produces a greater yield of sulphated acid mucopolysaccharides from elastotic dermis than from normal dermis, or (b) that these substances are depolymerized in elastotic dermis with alteration in their elution positions on ion-exchange resin chromatography, or (c) that a real increase in turnover of chondroitin-6-sulphate exists when elastin is being laid down.     

Imaging of melanin distribution using multiphoton autofluorescence decay curves

Background/purpose: Multiphoton fluorescence lifetime imaging (FLIM) is a technique that produces an image based on differences in the decay rate of fluorescence from a sample. Based on this method, the DermaInspect was developed to observe human skin components non-invasively. In this study, we used the DermaInspect to study melanin in skin.
Methods: A human three-dimensional skin model containing melanocytes was embedded in an OCT compound, frozen and sectioned at 10 μm. The melanin distribution in each section was visualized by the DermaInspect using time-resolved single-photon counting and near-infrared femtosecond laser pulse excitation. The melanin distribution of the same sections was then visualized using the Fontana-Masson staining method.
Results: High-resolution images were generated from the ratio of a ₁/ a ₂ ( a ₁e^{− t /120}+ a ₂e^{− t /1100} was chosen to express the exponential fluorescent decay curve) obtained using the DermaInspect. Granules with a high a ₁/ a ₂ ratio, approximately 1 μm in diameter, were observed. Fontana-Masson staining identified these granules as melanin. This new technique was then applied for in vivo observation of melanin in human skin. 'Melanin caps' were visualized in the basal cell layer around the nuclei in images derived from the a ₁/ a ₂ ratio.
Conclusion: Our study confirms that FLIM can non-invasively provide data of the melanin distribution with almost the same quality as the conventional Fontana-Masson staining method, and demonstrates that FLIM is useful for in vivo observation of melanin granules in human skin.