Preservation of epidermal melanocyte integrity in an ex vivo co-culture skin model with sebocytes.

A direct contact co-culture of skin explants to SZ95 sebocytes (3D-SeboSkin) has been shown to preserve the integrity of epidermal keratinocytes and dermis. In this study, the properties of epidermal melanocytes were evaluated in the same 3D SeboSkin ex vivo model. Skin explants (n = 6) were maintained in the 3D-SeboSkin model, in direct contact to fibroblasts and alone in serum-free medium (SFM). Histopathological, immunohistochemical, apoptosis and oil red staining evaluations were performed at Days 0 and 6 of incubation. Results revealed preservation and prominent proliferation of basal keratinocytes of the skin explants in addition to preservation of dermal collagen and vasculature at Day 6 in the 3D-SeboSkin culture model and to a lesser extent in co-culture with fibroblasts but not in SFM alone. Melan-A+/Ki67- epidermal melanocytes remained attached to the dermis even at sites of epidermal detachment in the three skin explant models tested. However, the number of epidermal melanocytes was significantly conserved in 3D-SeboSkin cultures in comparison with skin explants in SFM (p < 0.05), whereas no difference was found in comparison with the co-culture with fibroblasts. Few DAPI/TUNEL+ apoptotic melanocytes could mostly be observed in SFM-incubated skin explants. Furthermore, only SZ95 sebocytes in contact to skin explants in 3D-SeboSkin exhibited increased lipogenesis with accumulation of abundant lipid droplets. These results denote that the 3D-SeboSkin model yielded significant preservation of epidermal melanocytes and hence it is optimal for ex vivo studies of abnormalities of skin pigmentation, melanocyte neoplasms and effects of different hormones, cytokines, carcinogens and various therapeutics in a pattern that recapitulates the in vivo environment.

Drug reactions affecting hair and nails.

Drug-induced changes of hair and nails have been observed with a variety of different pharmaceutical agents, both topical and systemic. These compounds or their metabolites may interfere with hair cycling and texture, nail matrix, nail bed, nail folds, and microvasculature. Phototoxic reactions may also occur. Before initiating treatment, physicians and patients should be aware of possible adverse events to hair and nails and should be aware of the preventive measures, if available, as quality of life can be reduced, and adherence and compliance to treatment may be impaired.

Schistosomiasis (bilharziasis) and male infertility.

Schistosomiasis (bilharziasis) is an endemic parasitic disease of a major source of morbidity and mortality for developing countries. It is caused by different species of blood flukes (trematode worms) of the genus Schistosoma, the most important of which are S. haematobium which infests the genitourinary tract and S. mansoni and S. japonicum which infest the gastrointestinal tract. The incidence of schistosome-induced male infertility is not known and probably underestimated being overshadowed by the more severe and often fatal urinary and gastrointestinal complications. Several causes may contribute to schistosomiasis-induced male infertility, such as hormonal imbalance, testicular tissue damage and genital ductal system obstruction, in addition to decreased libido and erectile dysfunction due to associated hormonal imbalance and prostatic infestation. Demonstration of the schistosome ova in seminal plasma or testicular tissue confirms the diagnosis. Treatment of schistosomiasis-induced male infertility depends on clinical evaluation and includes, besides anthelmintic treatment, hormonal replacement and assisted reproduction (IVF/ICSI) in cases of severe oligozoospermia and or obstructive and nonobstructive azoospermia.

Schistosomiasis (Bilharziasis) ova: An incidental finding in testicular tissue of an obstructive azoospermic man.

Congenital bilateral absence of vas deferens (CBAVD) results in obstructive azoospermia in which testicular function, such as spermatogenesis, is preserved. Bilateral testicular biopsy is not only diagnostic but also therapeutic as retrieved spermatozoa are usually cryopreserved for assisted reproduction. In this case report, CBAVD was confirmed in a 24-year-old azoospermic man on the basis of persistent azoospermia associated with low semen volume, absent fructose and normal hormonal levels, ultrasonographically (absent seminal vesicles) and histologically (intact spermatogenesis). Interestingly and incidentally, only the right testicular biopsy showed ova of two parasitic species of Schistosoma, namely Schistosoma haematobium which infests the genitourinary tract and Schistosoma mansoni which infests the gastrointestinal tract. Both species are rare causes of azoospermia, and the case should be further managed as CBAVD in which the left testicle is considered the preferred site of sperm retrieval for assisted reproduction.

Surgical Treatment for Extramammary Paget's Disease.

OPINION STATEMENT: Extramammary Paget's disease (EMPD) is a rare, slow growing non-melanoma skin cancer.Diagnosis is often significantly delayed, since clinical presentation may resemble common benign dermatoses. Treatment is characterized by high recurrence rates. This is in part due to ill-defined margins and by frequent development of satellites. Improvement of outcome needs a better preoperative planning with fluorescence diagnostics or scouting biopsies. Mohs micrographic surgery has some advantages for patients, such as reduced relapse rates and prolonged relapse-free survival. Improved identification of Paget cells in cryosections by immunostainings or alternatively the use of delayed Mohs with formalin-fixed material reduces the rate of false-negative results. Surgery remains the cornerstone of treatment.

Role of adipose tissue in facial aging.

Age-dependent modification of the facial subcutaneous white adipose tissue (sWAT) connected with reduction of its volume, modification of collagen content and adhesion between dermal and adipose layers can significantly influence mechanical stability of the skin and cause the development of aging symptoms such as wrinkles. Typical aging appearance in facial skin is at least partly connected with special phenotypical features of facial preadipocytes and mature adipocytes. In this paper, we have discussed the possible roles of local inflammation, compartmental structure of facial sWAT and trans-differentiation processes such as beiging of white adipocytes and adipocyte-myofibroblast transition in facial skin aging.

Increased Activity and Number of Epidermal Melanocytes in Lesional Psoriatic Skin.

BACKGROUND: Psoriatic lesions may resolve with hypo- or hyperpigmentation. The involvement of melanocytes in this dichotomous clinical outcome is not fully investigated. OBJECTIVES: Qualitative and quantitative assessment of melanocytes in untreated lesional and non-lesional psoriatic skin (n = 15) and healthy controls (n = 10). METHODS: Skin biopsies were labelled immunohistochemically (APAAP technique) with the antimelanocyte monoclonal antibodies (MoAbs) HMB45, Melan A, tyrosinase and microphthalmia-associated transcription factor (MITF). The labelled melanocytes were evaluated by an independent investigator with a digital image analyser. RESULTS: Lesional melanocytes, in contrast to those in non-lesional and healthy skin, exhibited features of activation in the form of dilatation, prominent and long dendrites and intense labelling. The number of melanocytes was significantly increased in psoriatic lesions in comparison with non-lesional psoriatic and healthy skin as shown by counts of cells labelled with the MoAbs HMB45 (3-fold; p < 0.001), Melan A (1.6-fold; p < 0.01) and tyrosinase (1.5-fold; p < 0.01). In contrast, labelling with MITF revealed no significant difference (1.2-fold increase; p > 0.05). Likewise, no significant difference between non-lesional psoriatic and healthy skin control was found (p > 0.05). Furthermore, no positively labelled dermal cells were detected, apart from few only detected with Melan A. CONCLUSIONS: Epidermal melanocyte activity and numbers are increased in the epidermal compartment of psoriatic lesions providing an explanation for postinflammatory hyperpigmentation.

Skin manifestations of growth hormone-induced diseases.

The human skin is a well-organized organ bearing different types of cells in a well-structured interference to each other including epidermal and follicular keratinocytes, sebocytes, melanocytes, dermal papilla cells and fibroblasts, endothelial cells, sweat gland cells as well as nerves. Several hormones act on different cell types of the skin, while it is also considered an endocrine organ secreting hormones that act at several sites of the organism. GH receptors are found in almost all cell types forming the skin, while IGF-1 receptors' expression is restricted to the epidermal keratinocytes. Both Growth Hormone (GH) excess, as in the case of Acromegaly in adults, or Gigantism in growing children, and GH deficiency states lead to skin manifestations. In case of GH excess the main dermatological findings are skin thickening, coarsening of facial features, acrochordons, puffy hands and feet, oily skin and hyperhidrosis, while GH deficiency, on the contrary, is characterized by thin, dry skin and disorder of normal sweating. Moreover, special disorders associated with GH excess may have specific characteristics, as is the case of café-au-lait spots in Neurofibromatosis, or big café-au-lait skin hyperpigmented regions with irregular margins, as is the case in McCune-Albright syndrome. Meticulous examination of the skin may therefore contribute to the final diagnosis in cases of GH-induced disorders.

SZ95 sebocytes induce epidermal melanocyte dendricity and proliferation in vitro.

The regulatory effects of sebocytes on melanocytes (HMel) are unknown. In this study, SZ95 sebocytes co-cultured with HMel, whether in direct cell contact or with SZ95 sebocytes in inserts, resulted in epidermal HMel flattening with increase in surface area and multiple small dendrites formation. Only in high Ca(2+) level and direct cell contact co-culture, the HMel dendrites were remarkably long and preferentially targeted and attached to SZ95 sebocytes. Likewise, only high Ca(2+) SZ95 sebocyte conditioned medium stimulated HMel proliferation in a time-dependent manner at days 9 (142.9%, P < 0.01) and 12 (179.2%, P < 0.0001) of incubation when compared with day 0. In contrast, melanin contents significantly decreased on incubation with high Ca(2+) SZ95 sebocytes in comparison with low Ca(2+) SZ95 sebocytes at days 6 (P < 0.01) and 9 (P < 0.05) of incubation. These results denote that sebocytes also modulate HMel functions and may contribute to skin colour in sebaceous glands-rich body regions.

Cutaneous mononuclear cells and eosinophils are significantly increased after warm water challenge in pruritic areas of polycythemia vera.

BACKGROUND: Increased cutaneous cells following warm water challenge in pruritus-related polycythemia vera (PV) have been reported, but their nature and magnitude are not known. METHODS: Qualitative and quantitative assessments (digital image analysis) of the cutaneous mononuclear cells, eosinophils and mast cells were carried out in PV patients and healthy controls (n = 10 each) following exposures to water at room temperature and warm water. RESULTS: Infiltration of the spongiotic epidermis and dermis by mononuclear cells and eosinophils together with edema and vasodilatation of upper dermis following warm water contact was clearly observed only in PV patients. In contrast to controls, significant increase in numbers of mononuclear cells and eosinophils in comparison with exposure to water at room temperature at the dermal-epidermal junction (p < 0.01), papillary dermis (p < 0.01) and perivascular area (p < 0.05) was found. Obvious mast cell degranulation was seen in PV sections after warm water contact, but no significant increase of their numbers was observed whether among PV patients or healthy controls (p > 0.05). However, the numbers of papillary dermal mast cells in specimens obtained from PV patients following room temperature water exposure were significantly more than those of healthy controls (p < 0.05). CONCLUSIONS: PV represents an invisible dermatosis in which the infiltrating mononuclear cells and eosinophils may have a role in warm water-induced pruritus.

Receptors of eccrine, apocrine, and holocrine skin glands.

Skin glands are highly active miniorgans of skin that fulfill a diversity of functions. To coordinate metabolic and secretory activity, they express specific receptors. Recent investigations reveal expression of nuclear hormone receptors, neuropeptide receptors, cytokine receptors, and receptors for peptides of the transforming growth factor superfamily. There is evidence of not only central control, but also autocrine mechanisms of skin glands activity. The knowledge of ligand receptor interactions in these specialized skin structures might offer not only a better understanding of their pathology, but also new therapeutic options.

Topical pimecrolimus for skin disease other than atopic dermatitis.

Pimecrolimus is an ascomycin macrolactam. It is a specific calcineurin inhibitor that allows topical application. The highly lipophilic nature of this compound reduces the risk of systemic absorption through normal and inflammed skin. Pimecrolimus shows activity not only against T-cell activation, but also against mast cells and pruritus. Pimecrolimus 1% cream is approved for atopic dermatitis, and also has a great potential in other inflammatory skin diseases. Clinical trials have been performed in contact- and seborrhoeic dermatitis, genital lichen sclerosus, intertriginous psoriasis and cutaneous lupus erythematosus. In other diseases, the available data are limited to small case series, or individual cases of graft-versus-host disease or Netherton's disease. Although the use of calcineurin inhibitors in the treatment of vitiligo is promising, detailed studies with pimecrolimus and ultraviolet-irradiation are necessary and there is a need for prospective randomised, double-blind controlled trials.

A review of the microcirculation in skin in patients with chronic venous insufficiency: the problem and the evidence available for therapeutic options.

Impairment of the cutaneous microcirculation is a major predisposing factor in inflammation and ulceration in patients with chronic venous insufficiency (CVI). Increase of capillary filtration rate predisposes to the formation of edema. Local lymphedema is a complication of CVI, often underdiagnosed. This review is focused on CVI but excludes the complication of ulceration. Treatment of microcirculatory dysfunction can be done by pharmacologic intervention or compression therapy or using a combination of both. This review is focused on drugs that have been evaluated by randomized prospective controlled trials. The following compounds are discussed: horse chestnut seed extracts, flavonoids, red vine leaves extracts, total triterpenic fraction of Centella asiatica (L), prociadins, calcium dobesilate, and pentoxifylline. The microcirculatory effects of compression therapy using bandages or stockings are also reviewed. The major microcirculatory effects that have been shown are the reduction of capillary filtration rate and improvements in levels of transcutaneous partial pressures of oxygen and carbon dioxide (TcPO(2) and TcPCO(2)). Available data suggest that a combination of pharmacologic and compression therapy may have some additive effects.

Patients with papular urticaria have IgG antibodies to bedbug (Cimex lectularius) antigens.

IgG and IgE against salivary gland proteins of bedbug (Cimex lectularius) were assessed in comparison with mosquito (Culex pipiens) and flea (Pulex irritans) antigens in the sera of papular urticaria patients (group I), siblings without papular urticaria (group IIa), patients' parents (group IIb), and healthy controls (group III) (Immunoblotting). Anti-C. lectularius IgG was significantly recognized at 66 and 10 kDa in 40% of group I, besides others ranging from 45 to 107 kDa. Group IIa significantly reacted with 70 kDa (57.1%). Group IIb reacted with 21 and 8.5 kDa (26.7%). Sixty percent of group IIb and 100% of group III significantly identified a band of 12.5 kDa. IgG against C. pipiens was significantly recognized at a range of 18-105 kDa in group I, IIb (115, 7 kDa), and III (58, 50 kDa). Anti-P. irritans IgG was significantly recognized by group I (100, 70 kDa) and group IIa (60, 35 kDa). IgE response was confined to C. pipiens at 115 and 54 kDa in groups I and III, respectively, besides 68 and 58 kDa in group IIa. It is concluded that IgG is present against C. lectularius, C. pipiens, and P. irritans in papular urticaria and may contribute to its pathogenesis.

Common dermatoses in moderately pigmented skin: uncommon presentations.

Several common dermatoses appear different in people of color. Most international literature, especially the reputed textbooks, are replete with photographs of skin diseases in fair-skinned patients. The orientation of Western dermatologists to common diseases in pigmented skin therefore is needed. The reverse is also true. Dermatologists who work in pigmented skin communities are known to have initial problems with fair skin. It is therefore important to have a judicious balance of entities seen in both of these skin types in major international literature, especially in textbooks. In addition, common dermatoses may appear strange and confusing particularly when they are in their advanced form. People with pigmented skin living in developing countries often present with diseases that appear greatly altered, because of various reasons. Main ones are treatment taken at home with household remedies, especially topical therapy, inappropriate treatment given by general practitioners with sparse knowledge of dermatology, and injudicious steroid use. All these factors lead to exacerbation of the disease or superimposed irritation or infection, which all contribute to a different appearance. Equally important is the delay in seeking treatment because of financial constraints.

Leg ulcers are a diagnostic and therapeutic challenge.

Leg ulcers are common. They cause a substantial burden to the patient and society. However, there is no need for therapeutic nihilism. The target of leg ulcer therapy is the individual patient. To be treated in a rational and successful way, exact diagnosis of the underlying cause(s) and associated diseases is necessary. This can be done in the most effective way with an interdisciplinary approach. The collection of cases demonstrates the need for careful clinical investigation substantiated and supported by vascular, histopathologic, and microbiologic techniques whenever needed. It is difficult to heal every ulcer completely, but improvement of the medical situation as well as the quality of life of the patient is possible in most cases.

Pharmacotherapy of pompholyx.

Pompholyx is an inflammatory vesicobullous disorder of the palms and soles. The condition is difficult to treat because of the peculiarities of the affected skin, namely, the thick horny layer and richness of sweat glands. The cornerstones of topical therapy are corticosteroids, although calcineurin inhibitors seem to be effective as well. Topical photochemotherapy with 8-methoxypsoralen is as effective as systemic photochemotherapy or high-dose ultra violet Type A-1 irradiation. Systemic therapy is often necessary in bullous pompholyx. Corticosteroids are used commonly, although no controlled studies have been published. For recalcitrant cases corticosteroids are combined with immunosuppressants. A new evolving treatment seems to be the intradermal injection of botulinum toxin.