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Objective:To evaluate the safety and performance of Alione Hydrocapillary dressing (Coloplast A/S) in the management of highly exuding chronic venous leg ulcers and compare it with two hydropolymer dressings, Tielle and Tielle Plus (Johnson & Johnson).Method:A comparative clinical trial was conducted on 97 patients with an ankle brachial pressure index ≥0.8 and a highly exuding leg ulcer. Ulcer duration was at least four weeks. Treatment continued until healing or for a maximum of 12 months.Results:There was no statistically significant difference in healing time or wound area reduction between the two treatment protocols. The test dressing (Alione Hydrocapillary) had better absorption capacity and was more comfortable for the patients than the comparator dressings (Tielle/Tielle Plus) and adhered less to the wound bed. Also, more patients preferred the test dressing to their previous treatment. Although severe leakage and maceration were observed more frequently in the comparator group compared with the test group, this was not statistically significant.Conclusion:Both treatment protocols were safe and effective in treating highly exuding chronic venous leg ulcers. The test dressing performed as well as or better than the comparator dressings for all study parameters and more patients preferred the test dressing to their previous dressing compared with the comparator dressings.Declaration of interest:The study was funded by Coloplast A/S, Humlebaek, Denmark.

Recently, microvascular channels, as detected by PAS histochemistry, were positively correlated with poor prognosis in uveal malignant melanoma. Since uveal melanomas are not penetrated by lymphatic vessels, while cutaneous melanomas are, the question arises as to whether these loops and networks are also of prognostic relevance in cutaneous melanoma. Histochemically and immunohistochemically detected loops and networks in 100 cases of cutaneous malignant melanoma were correlated with the occurrence of metastasis in a 10-year follow-up study. To detect these patterns, the significance of various methods (PAS reaction with/without nuclear counterstain, anti-laminin immunohistochemistry) was investigated. The presence of loops and networks was a highly significant prognostic marker (p<0.0001) for metastasis in cutaneous malignant melanoma. The presence of these patterns proved to have higher prognostic relevance for metastasis than Breslow's tumour thickness, especially for stage IB and stage IIA tumours (intermediate thickness/risk). PAS reaction without nuclear counterstain proved to be the best method to detect these patterns. Compared with the conventional staging of Breslow's tumour thickness, and especially so for stage IB and IIA melanomas, the determination of PAS-positive loops and networks in cutaneous malignant melanoma provides additional prognostic information. Copyright © 2001 John Wiley & Sons, Ltd.

A new hydropolymer dressing was compared with an alginate dressing in a multicentre, prospective, controlled, randomised, stratified, open label trial of 113 patients with exuding venous leg ulcers. The study aimed to evaluate the performance of the dressings in terms of their ability to handle exudate, patient and user acceptability and cost-effectiveness. Patients were stratified according to volume of wound exudate (moderate/heavy) and randomised to the hydropolymer dressing or the alginate plus a secondary dressing.A statistically significant difference between treatment groups was observed in mean wear time, with a longer wear time observed in the hydropolymer group (3.91 days) compared with the alginate group (3.09 days, p=0.001). In terms of patient and user acceptability, all 10 overall evaluations made by both patient and investigator were markedly in favour of the hydropolymer dressing (p<0.001 to p=0.020).The use of the hydropolymer dressing for patients with moderate to heavily exuding venous leg ulcers has statistically significant advantages over the alginate dressing in terms of wear time and investigator and patient acceptability. It is anticipated that this reduction in dressing frequency will translate into a cost-effective wound treatment.

The adaptation of mRNA stability to environmental changes is a means of cells to adjust the level of gene expression. The Escherichia coli ompA mRNA has served as one of the paradigms for regulated mRNA decay in prokaryotes. The stability of the transcript is known to be correlated inversely with the bacterial growth rate. Thus, the regulation of ompA mRNA stability meets the physiological needs to adjust the level of ompA expression to the rate of cell division. Recently, host factor I (Hfq/HF1) was shown to be involved in the regulation of ompA mRNA stability under slow growth conditions. Here, we present the first direct demonstration that 30S ribosomes bound to the ompA 5'-UTR protect the transcript from RNase E cleavage in vitro. However, the 30S protection was found to be abrogated in the presence of Hfq. Toeprinting and in vitro translation assays revealed that translation of ompA is repressed in the presence of Hfq. These in vitro studies are corroborated by in vivo expression studies demonstrating that the reduced synthesis rate of OmpA effected by Hfq results in functional inactivation of the ompA mRNA. The data are discussed in terms of a model wherein Hfq regulates the stability of ompA mRNA by competing with 30S ribosomes for binding to the ompA 5'-UTR.

Abstract We recently established a skin organ culture model for epithelial healing by creating a central defect in freshly excised human skin specimens and keeping them in culture for up to 7 days, either untreated or with transplantation of allogenic or autologous keratinocytes. In this study the molecular diversity of cell-cell junction proteins in the regenerating epidermis was analysed immunohistochemically using a broad spectrum of monoclonal antibodies against glycoproteins (cadherins) and plaque proteins of desmosomes. At all stages studied the entire set of desmosomal cadherins [desmogleins (Dsg) 1–3 and desmocollins (Dsc) 1–3] was detected, with Dsg3, Dsc2 and Dsc3 being the most prominent. In the disordered neoepithelium at day 3 (after transplantation) some desmosomal cadherins appeared in their respective stratum compartments. In regenerating epidermis on day 7, which exhibited a more ordered stratification and a compact horny layer, stratification-related patterns of desmosomal cadherins were more pronounced. However, some immaturity of the day-7 neoepidermis was reflected by relatively low levels of the maturation-associated Dsg1 and Dsc1 and a strong basal layer expression of Dsg2 which is sparse in normal epidermis. Desmosomal plaque proteins showed expression patterns similar to those in normal healthy epidermis. The adherens junction-related E-cadherin was also detected. Dendritic cells (melanocytes, Langerhans cells) were mainly present at the wound margins. In conclusion, this study demonstrated partial but not complete epidermal maturation and junction development during regeneration up to day 7. This model should also be useful in future studies to evaluate the effects of growth hormones to be used in therapeutic trials on chronic leg ulcers.:

In normal skin, cytokeratin polypeptides are expressed in different cell-type-specific patterns, in the keratinocytes of the different epidermal cell strata as well as in different lateral epithelial domains. Using light microscopically controlled microdissection of defined regions from frozen sections of biopsies, we have prepared cytoskeletons of various benign and malignant keratinocyte-derived tumors of human skin and analyzed their cytokeratin polypeptide patterns by two-dimensional gel electrophoresis. Premalignant fibro-epitheliomas and basal cell epitheliomas display a relatively simple cytokeratin pattern (cytokeratins nos. 5, 14, 15, and 17). Pseudocarcinomatous hyperplasia, some squamous cell carcinomas, and a certain subtype of condylomata acuminata present a hair-follicle-like pattern (nos. 5, 6, 14, 16, 17). In addition to these components, variable, mostly low amounts of cytokeratins nos. 1 (Mr 68,000), and 11 are detected in most squamous cell carcinomas, in keratoacanthomas, verruca vulgaris, and another type of condylomata acuminata. In molluscum contagiosum, verruca plana, solar keratosis, and seborrheic keratosis, the cytokeratin expression is shifted more towards the normal epidermal pattern (polypeptides nos. 1, 2, 5, 10, 11, 14, 15 and traces of nos. 6 and 16 in the latter two tumors). No tumor-specific cytokeratins have been found. We conclude that keratinocyte-derived skin tumors contain various combinations of cytokeratins of the subset typical for normal keratinocytes of skin, but no cytokeratins typical for internal, simple epithelia. Different groups of tumors can be distinguished by their specific cytokeratin patterns. Possible applications of cytokeratin typing in clinical diagnosis are discussed.

Merkel cells (MCs), the neuroendocrine cells of the skin cannot be identified with certainty using conventional light microscopic staining methods. Using immunoperoxidase microscopy with antibodies specific for cytokeratin 18, which has been established as a marker protein of MCs, we have evaluated the numbers of MCs per mm2 skin in normal and sun-damaged upper arm skin. The sun-exposed skin contained twice as many MCs as the not sun exposed skin. Further quantification of MC density at various body sites (trunk, leg) showed a rather variable but often unexpectedly high MC density. The possible role of MC in development of actinic elastosis is discussed.

Human eccrine sweat gland ducts and benign and malignant eccrine poromas were studied for the expression of various cytokeratins (CK) and vimentin by applying immunoperoxidase and immunofluorescence microscopy to frozen or paraffin-embedded sections, and using two-dimensional gel electrophoresis and immunoblotting. In acrosyringia and dermal eccrine ducts, the luminal cells exhibited intense staining for CKs 1/10/11 and 19. The periluminal cell layers of acrosyringia contained CKs 1/10/11, while CK 5 was absent. In contrast, the basal cell layer of dermal ducts was only positive with the antibody against CK 5, i. e. a pattern resembling that seen in epidermal basal cells. CK 9 was detected only in keratinocytes peripherally surrounding acrosyringia. In benign poromas, gel electrophoresis revealed that CKs 5 and 14 were predominant, with CKs 6, 16 and 17 being minor components. At the immunohistochemical level CKs 1/10/11 and 19 could be further detected with varying frequency in scattered or clustered cells and/or duct-like structures. Occasionally, CK 9-positive cells were observed. Malignant poromas displayed a similar overall gel-electrophoretic pattern. Their immunohistochemical staining patterns were also similar to (albeit rather more variable than) those seen in benign poromas. Our results show that, with respect to their CK expression pattern, the majority of poroma cells resemble the basal cells of both the dermal ducts and the epidermis, while only minor and variable subpopulations acquire features present in ductal/acrosyringial luminal cells that would be indicative of poral differentiation. Thus, the matrix cells of poromas seem to be most closely related to basal cells located at the transition between the glandular epidermal ridge and dermal eccrine duct, being in no way analogous to the cells of the adult acrosyringium above the basal cell level.

Merkel cells (MC) were identified immunohistochemically using antibodies specific for cytokeratin (CK) 20 within human epidermis 12 to 72 h after exposure to UVB (4 MED). 12 h after exposure all MC were normally localized within the epidermal basal layer. However, 24 h after exposure 4% of the MC were detected suprabasally, the remaining 96% still being situated in the basal layer. Surprisingly, at 48 h and 72 h more than 50% had lost contact with the basal membrane. The MC of hair follicles did not show any obvious changes. These results argue, in the context of acute epidermal UV damage, for an abnormal turnover in dermatitis.

Digital skin of human fetuses is known to contain a particularly high concentration of Merkel cells. Using antibodies against the simple epithelial cytokeratins (CK) 18 and 20, which are sensitive and specific Merkel cell markers, we studied imiminohistochemically the main adnexal structure of digital skin, the nail anlage, in human fetuses (9–22 weeks of gestation) for the presence of Merkel cells. As early as week 9 some clustered Merkel cells were detected in the early matrix primordium. In specimens of week 12–15, abundant Merkel cells were found in the nail anlagen, particularly in the epithelium of the proximal nail-fold and the dorsal and ventral side of the apex region. In contrast, Merkel cells were essentially absent from the epithelium of the ventral matrix (surface-near portion), lunula and nail bed. Correspondingly, in these regions, the adjacent dermis contained hardly any nerve fibres, whereas such fibres, as detected by neurofilament antibodies, were quite numerous adjacent to the proximal nail-fold epithelium. At week 22, the Merkel cell number in the nail anlage had decreased, and in adult nail matrix such cells were very rare. No Merkel cells were found in the dermal tissue surrounding the nail anlage while finger-tip skin of week 15, and particularly of week 22, exhibited single Merkel cells in the upper dermis next to clusters of such cells in the glandular ridges. We also found that Merkel cells were negative for CK 17. These results suggest a possible role for fetal Merkel cells in the proper development of sensory nerve fibres, while they do not seem to be important for the growth of trichocytic tissues, i.e. the hair bulb and the trichocytic portion of the nail anlage.

Abstract: The fetal development of Merkel cells – neuroendocrine cells of the skin – has been a matter of debate for a long time. Recent results have helped to confirm their intraepidermal development in humans. Simple epithelial cytokeratins (CK) nos. 8, 18, 19 and 20 are well established markers at the light microscopic level. These cells could be detected from fetal week 8 within the epidermis with an enormous increase during the following weeks. This gives rise to the question as to whether Merkel cells are undergoing mitoses or whether they are derived from basal keratinocytes. We studied fetal and adult skin using antibodies to simple epithelial CK and to Ki67, a human nuclear cell proliferation-associated antigen in an attempt to answer these questions. In human adult and fetal skin of various stages we could not detect any Merkel cells undergoing cell division. These results suggest that Merkel cells are postmitotic cells to be renewed from undifferentiated keratinocytes with stem cell characteristics.

Abstract. Objective: To study the immunoneurocrine network in inflammatory dermatoses, we investigated histochemically acute UV and acute contact dermatitis.¶Methods: Antibodies were applied to frozen and paraffin specimens of human skin after irradiation (n = 10), to positive patch tests (n = 10) and controls (n = 10) against: HSP 70, 72, 27, neuronal polypeptides (α-MSH, NSE, bombesin, PGP 9.5, NGF, NGF-R) and intermediate filaments (peripherin, NF 200, CK 19, 20).¶Results: HSPs and α-MSH were upregulated in UV dermatitis in the epidermis compared to contact dermatitis and normal skin. Sunburn cells did not express HSPs or α-MSH in UV dermatitis. Neuronal markers and HSP 27 labeled more nerve fibers in UV than in contact dermatitis, except the increased staining for NGF, NGF-R and α-MSH in nerve fibers in contact dermatitis. In UV dermatitis, 50% of Merkel cells were suprabasal, but in contact dermatitis, basal, rounded and reduced in number.¶Conclusions: Merkel cells, HSPs and markers of neuroinflammation are of different importance in UV and contact dermatitis in vivo.

The skin, the largest organ of the body, is an essential barrier that under homeostatic conditions efficiently protects and/or minimizes damage from both environmental (e.g. microorganisms, physical trauma, ultraviolet radiation) and endogenous (e.g., cancers, inflammation) factors. This formidable barrier function resides mainly in the epidermis, a dynamic, highly-stratified epithelium. The epidermis has 2 major barrier structures: stratum corneum, the outmost layer and tight junctions, intercellular junctions that seal adjacent keratinocytes in the stratum granulosum, found below the stratum corneum.In recent years there have been significant advances in our understanding of tight junction function, composition and regulation. Herein we review what is known about tight junctions in healthy skin and keratinocyte culture systems and highlight the dynamic crosstalk observed between tight junctions and the cutaneous immune system. Finally we discuss the preliminary observations suggesting that tight junction function or protein expression may be relevant for the pathogenesis of a number of common cutaneous inflammatory and neoplastic conditions.